Extensive and detailed clinical highlights on Diabetes Mellitus

all about Diabetes

The liver is one of the target organ of Insulin
The liver is one of the target organ of Insulin
Adipocytes are another target cells for insulin
Adipocytes are another target cells for insulin
The Muscles are another target organs of the Insulin Hormone
The Muscles are another target organs of the Insulin Hormone
The brain is one of the main target organs of Insulin.
The brain is one of the main target organs of Insulin.
Blood cells are not targeted by Insulin
Blood cells are not targeted by Insulin
Some ethnic groups stand the risk of acquiring diabetes mellitus
Some ethnic groups stand the risk of acquiring diabetes mellitus
A coma patient. Clinical sign of the severe stage of Diabetes
A coma patient. Clinical sign of the severe stage of Diabetes
Dehydration is another clinical sign of Diabetes
Dehydration is another clinical sign of Diabetes
Lethargy and dizziness is another clinical factor of moderate to severe stages of diabetes.
Lethargy and dizziness is another clinical factor of moderate to severe stages of diabetes.
Fats of an obesed person who stands the risk of getting diabetes Mellitus
Fats of an obesed person who stands the risk of getting diabetes Mellitus
glycogenolysis pathway
glycogenolysis pathway
People above the age of 45 stand the risk of Diabetes type II
People above the age of 45 stand the risk of Diabetes type II
Patients with Myocardial Infarction also stand the risk
Patients with Myocardial Infarction also stand the risk
Obese people stand the risk as well
Obese people stand the risk as well
Pregnancy is a very well known precipitating factor of diabetes mellitu
Pregnancy is a very well known precipitating factor of diabetes mellitu
The retina is one of the cells not targeted by insulin
The retina is one of the cells not targeted by insulin
Stroke is another etiology
Stroke is another etiology
surgery is a precipitating factor of Diabetes Mellitus
surgery is a precipitating factor of Diabetes Mellitus
trauma is another precipitating factor of Diabetes Mellitus
trauma is another precipitating factor of Diabetes Mellitus

INTRODUCTION.....

Hello guys! Welcome to the first treatment experience of the endocrinology department of my internet Hospital. Before we kick off, I would like to encourage you that this is a very interesting, detailed, extensive and 'complete' hub about the clinical and medical evaluation of Diabetes Mellitus. Before you read on, I will urge you to take a look at the link below for a better preamble of what you are to expect here in this hub. You could open it in another tag, so that you can easily come back to this well-informative page about Diabetes. Here is the link

Diabetes Mellitus in simple plain language

When you are done, you can come back here to continue. Here are the highlights of what you are to expect:

1. Introduction to Diabetes Mellitus (Physiology of Insulin)

2. Action of Insulin

3. Type 1 Diabetes

4. Type 2 Diabetes

5. Pathogenesis and clinical difference between Type 1 and Type 2

6. Etiologic classification of Diabetes Mellitus

7. Stages of Diabetes Mellitus development

8. Degrees of severity of Diabetes Mellitus

9. Physical examination of a patient with DIabetes Mellitus

10. Atherosclerosis in Diabetes Mellitus

11. Allergic reactions

12. Diabetic Blisters

13. Diagnosis of Diabetes Mellitus

14. Long term complications of Diabetic Mellitus which includes sexual problems in men (Erectile dysfunction and retrogade ejaculation) and sexual problems in women (decreased vaginal Lubrication and decreased or Absent sexual responses)

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INSULIN PHYSIOLOGY

The pancreas is an elongated organ nestled next to the first part of the small intestine. The endocrine pancreas refers to those cells within the pancreas that synthesize and secrete hormones.

The endocrine portion of the pancreas takes the form of many small clusters of cells called islets of Langerhans or, more simply, islets. Humans have roughly one million islets. In standard histological sections of the pancreas, islets are seen as relatively pale-staining groups of cells embedded in a sea of darker-staining exocrine tissue.

Pancreatic islets house three major cell types, each of which produces a different endocrine product:

· Alpha cells (A cells) secrete the hormone glucagon.

· Beta cells (B cells) produce insulin and are the most abundant of the islet cells.

Delta cells (D cells) secrete the hormone somatostatin, which is also produced by a number of other endocrine cells in the body.

Interestingly, the different cell types within an islet are not randomly distributed - beta cells occupy the central portion of the islet and are surrounded by a "rind" of alpha and delta cells. Aside from the insulin, glucagon and somatostatin, a number of other "minor" hormones have been identified as products of pancreatic islets cells.

Islets are richly vascularized, allowing their secreted hormones ready access to the circulation. Although islets comprise only 1-2% of the mass of the pancreas, they receive about 10 to 15% of the pancreatic blood flow. Additionally, they are innervated by parasympathetic and sympathetic neurons, and nervous signals clearly modulate secretion of insulin and glucagon.

The term Diabetes Mellitus refers to the excretion of large quantities of sweet urine. Diabetes is an old word for siphon and means “dieresis”, mellitus means “sweet”. The clinical syndrome known as DM comprises a wide variety of symptoms, physical findings and laboratory abnormalities, in which multiple etiologic factors are involved, the pathophysiology is partly understood and treatment is unsatisfactory. The hallmark of DM is hyperglycemia.

Diabetes Mellitus (DM) – is endocrine – metabolic disease, which develops due to absolute or relative insulin insufficiency and characterized by chronic hyperglycemia, changes of different systems and organs of patient.

Insulin is a rather small protein, with a molecular weight of about 6000 Daltons. It is composed of two chains held together by disulfide bonds.

Insulin is secreted in primarily in response to elevated blood concentrations of glucose. This makes sense because insulin is "in charge" of facilitating glucose entry into cells. Some neural stimuli (e.g. sight and taste of food) and increased blood concentrations of other fuel molecules, including amino acids and fatty acids, also promote insulin secretion.

Our understanding of the mechanisms behind insulin secretion remain somewhat fragmental. Nonetheless, certain features of this process have been clearly and repeatedly demonstrated, yielding the following model:

· Glucose is transported into the B cell by facilitated diffusion through a glucose transporter; elevated concentrations of glucose in extracellular fluid lead to elevated concentrations of glucose within the B cell.

· Elevated concentrations of glucose within the B cell ultimately leads to membrane depolarization and an influx of extracellular calcium. The resulting increase in intracellular calcium is thought to be one of the primary triggers for exocytosis of insulin-containing secretory granules. The mechanisms by which elevated glucose levels within the B cell cause depolarization is not clearly established, but seems to result from metabolism of glucose and other fuel molecules within the cell, perhaps sensed as an alteration of ATP:ADP ratio and transduced into alterations in membrane conductance.

· Increased levels of glucose within B cells also appears to activate calcium-independent pathways that participate in insulin secretion.

Stimulation of insulin release is readily observed in whole animals or people. The normal fasting blood glucose concentration in humans and most mammals is 80 to 90 mg per 100 ml, associated with very low levels of insulin secretion.

Immediately after the increasing the level of glycemia begins, plasma insulin levels increase dramatically. This initial increase is due to secretion of preformed insulin, which is soon significantly depleted. The secondary rise in insulin reflects the considerable amount of newly synthesized insulin that is released immediately. Clearly, elevated glucose not only simulates insulin secretion, but also transcription of the insulin gene and translation of its mRNA.

Physiologic effects of insulin

Stand on a streetcorner and ask people if they know what insulin is, and many will reply, "Doesn't it have something to do with blood sugar?" Indeed, that is correct, but such a response is a bit like saying "Michael Jackson? Wasn't he some kind of a musician?"

Insulin is a key player in the control of intermediary metabolism. It has profound effects on both carbohydrate and lipid metabolism, and significant influences on protein and mineral metabolism. Consequently, derangements in insulin signalling have widespread and devastating effects on many organs and tissues.

THE ACTION OF INSUIN

Insulin is an anabolic hormone (promotes the synthesis of carbohydrates, proteins, lipids and nucleic acids).

The most important target organs for insulin action are:

- liver

- muscles

- adipocytes.

The brain and blood cells are unresponsive to insulin.

Insulin and Carbohydrate Metabolism

Glucose is liberated from dietary carbohydrate such as starch or sucrose by hydrolysis within the small intestine, and is then absorbed into the blood. Elevated concentrations of glucose in blood stimulate release of insulin, and insulin acts on cells thoughout the body to stimulate uptake, utilization and storage of glucose. The effects of insulin on glucose metabolism vary depending on the target tissue.

The effects of insulin on carbohydrate metabolism include:

1. Insulin facilitates entry of glucose into muscle, adipose and several other tissues.

2. Insulin stimulates the liver to store glucose in the form of glycogen .

3. Insulin inhibits glucose formation – from glycogen (glycogenolysis) and – from amino-acid precursors (glyconeogenesis).

As a result - well-known effect of insulin is to decrease the concentration of glucose in blood, which should make sense considering the mechanisms described above. Another important consideration is that, as blood glucose concentrations fall, insulin secretion ceases. In the absence of insulin, a bulk of the cells in the body become unable to take up glucose, and begin a switch to using alternative fuels like fatty acids for energy. Neurons, however, require a constant supply of glucose, which in the short term, is provided from glycogen reserves.

In the absence of insulin, glycogen synthesis in the liver ceases and enzymes responsible for breakdown of glycogen become active. Glycogen breakdown is stimulated not only by the absence of insulin but by the presence of glucagon, which is secreted when blood glucose levels fall below the normal range.

Insulin and Protein Metabolism:

1. Insulin transfers of amino acids across plasma membranes.

2. Insulin stimulates of protein synthesis.

3. Insulin inhibites of proteolysis.

Insulin and Lipid Metabolism

The metabolic pathways for utilization of fats and carbohydrates are deeply and intricately intertwined. Considering insulin's profound effects on carbohydrate metabolism, it stands to reason that insulin also has important effects on lipid metabolism. Important effects of insulin on lipid metabolism include the following:

1. Insulin promotes synthesis of fatty acids in the liver.

2. Insulin inhibits breakdown of fat in adipose tissue (lipolisis) by inhibiting the intracellular lipase that hydrolyzes triglycerides to release fatty acids.

From a whole body perspective, insulin has a fat-sparing effect. Not only does it drive most cells to preferentially oxidize carbohydrates instead of fatty acids for energy, insulin indirectly stimulates accumulation of fat is adipose tissue.

Insulin and Nucleic acids Metabolism:

1. Insulin stimulates nucleic acid synthesis by stimulating the formation of adenosine triphosphate (ATP), DNA and RNF.

Other effects:

1. Insulin stimulates the intracellular flow of potassium, phosphate and magnesium in the heart.

2. Insulin inhibits inotropic and chronoropic action (unrelated to hypoglycemia).

The action of insulin can be decreased by:

- glucagons: stimulates glycogenolysis and glyconeogenesis;

- somatostatin: inhibits secretion of insulin and regulates glucose absorption from alimentary tract into blood;

- glucocorticoids: decrease of glucose utilization by tissues, stimulate glycogenolysis and glyconeogenesis, increase lipogenesis (in patients with insulinoresistancy);

- catecholamines (adrenaline): inhibits β-cells secretion, stimulates glycogenolysis and ACTH secretion;

- somatotropin: stimulates α-cells (which secret glucagon), increases activity of enzymes which destroy the insulin, stimulates glyconeogenesis, increases of glucose exit from the liver veins into blood, decreases of glucose utilization by tissues;

- ACTH: stimulates glucocorticoides secretion and β-cells secretion;

- thyroid hormones: increase glucose absorption into blood, stimulate glycogenolysis, inhibit fat formation from the carbohydrates.

Absolute insulin insufficiency means that pancreas produce insulin in very low quantities or doesn’t produce it at all (due to destruction of beta-cells by inflammative, autoimmune process or surgery).

Relative insulin insufficiency means that pancreas produces or can produce insulin but it doesn’t “work”. (The pathologic process can be on the next levels:

- beta cells: they can be not sensitive for the high level of glycemia;

- insulin: abnormal insulin, insulin antibodies, contrainsulin hormones, absence of enzyme, which activates proinsulin (into insulin));

- receptors (decreased receptor number or diminished binding of insulin).

The Pancreas and Insulin

It consists of the Beta cells (producing Insulin), the Alpha cells (Producing glucagon, the Delta cells (Producing the somastostatins) the gastrin producing cells and Pancreatic Polypeptides.
It consists of the Beta cells (producing Insulin), the Alpha cells (Producing glucagon, the Delta cells (Producing the somastostatins) the gastrin producing cells and Pancreatic Polypeptides.
The Insulin formula. It's Molecular weight is 6000. It consists of 51 amino acidic parts from 16 different amino-acids. The first most important biologic stimulator of Insuline secretion is the glucose.
The Insulin formula. It's Molecular weight is 6000. It consists of 51 amino acidic parts from 16 different amino-acids. The first most important biologic stimulator of Insuline secretion is the glucose.

Chronic Complications of Diabetes Mellitus

Classification of chronic (long-term) complications of DM.

I. Diabetic angiopathy:

1. Microangiopathy:

1) nephropathy;

2) retinopathy;

3) angiopathy of lower extremitas.

2. Macroangiopathy:

1) ischemic heart disease;

2) angiopathy of lower extremities.

II. Diabetic neuropathy:

1) central (encephalopathy);

2) peripheral;

3) visceral (dysfunction of inner organs).

The long-term degenerative changes in the blood, vessels, the heart, the kidneys, the nervous system, and the eyes as responsible for the most of the morbidity and mortality of DM. There is a causal relationship and the level of the metabolic control.

Diabetic retinopathy.

Background retinopathy (the initial retinal changes seen on the ophthalmoloscopic examination) does not significantly alter vision, but it can lead to processes that cause blindness (e.g., macular edema or proliferative retinopathy with retinal detachment or hemorrhage).

Evidence of retinopathy, rarely present at diagnosis in 1DM, is present in up to 20 % of type 2 DM patients at diagnosis. About 85 % of all diabetics eventually develop some degree of retinopathy.

Diabetic retinopathy is classified according to the changes seen at background during ophthalmoscopic examination with pupils dilated.

I. Nonproliferative or background retinopathy (it is usually the earliest sigh and consists of retinal microaneurysms, hard and soft exudates).

II. Maculopathy or preproliferative retinopathy (it is characterized by macular edema and/or hemorrhages).

III. Proliferative retinopathy (the hallmark of this complication is neovascularization, i.e., growth of new vessels in areas of hypoperfusion. Adhesion of the vessels to the vitreous leads to retinal detachment, vitreous hemorrhage and others. The prognosis is extremely poor. 5 years after recognition of this complication 50 % of the patients are blind).

The mechanisms involved in the development of retinopathy are not clearly known. Genetic predisposition, growth hormone, hypoxia, and metabolitic abnormalities particularly of lipids, have been implicated.

Diabetic nephropathy.

It is usually asymptomatic until end stage renal disease develops, but it can course the nephrotic syndrome prior to the development of uremia. Nephropathy develops in 30 to 50 % of type 1 DM patients and in small percentage of type 2 DM patients. Arteriolar hyalinosis, a deposition of hyaline material in the lumen of the afferent and efferent glomerular arterioles, is an almost pathognomic histologic lesion of DM.

Classificationof diabetic nephropathy by Mogensen.

I. Hyperfunction of kidneys. It is characterized by:

- increased renal blood circulation;

- increased glomerular filtration rate (GFR) (> 140 ml/min);

- hypertrophy of kidneys;

- normoalbuminuria (<30 mg/day).)

II. Stage of initial changes of kidney structure. It is characterized by:

- mesangial changes due to accumulation of immunoglobulins (IgG, IgM), complement and other nonimmunologic proteins (lipoproteins, fibrin);

- high GFR;

- normoalbuminuria.)

III. Initial nephropathy. (It is characterized by:

- microalbuminuria (30 to 300 mg/day);

- high or normal GFR;

- periods of blood hypertension.)

IV. Nephropathy or nephrotic stage. (It is characterized by:

- persistent proteinurea (>500 mg/day);

- normal or decreased GFR;

- persistent blood hypertension.)

V. Chronic renal failure or uremia.. It is characterized by:

Physical signs of chronic renal failure

- decreased GFR;

- blood hypertension;

- increased serum creatinine;

- signs of intoxication.

Diabetic angiopathy of lower extremities

Atherosclerosis of large vessels (macroangiopathy) leads to intermittent claudication, cold extremities and other symptoms which can be also find while arteriols and capillaries are affected (microangiopathy).

Classification of lower extremities’ angiopathy.

I. Nonclinic stage. (Changes could be find only during instrumental examination.)

II. Functional stage. (It is characterized by cold extremities, numbness, tingling, pain during physical examination.)

III. Organic stage. (It is characterized by trophyc changes: dry skin, hypo- or atrophy of muscles, ulcers, gangrene.)

Ischemic heart disease.

1. Cardiovascular changes tend to occur earlier in patients with DM when compared with individuals of the same age.

2. Frequency of myocardial infarction (MI) and mortality is higher in diabetics than that in nondiabetis og the same age.

3. The prognosis is even worse if ketoacidosis, or other complications of DM are present.

4. Diabetic patients have more complications of MI (arrhythmias, cardiogenic shock and others) than nondiabetic ones.

5. Often can observe atypical forms (without pain).

6. Male : female = 1 : 1 (nondiabetics = 10 : 1).

Diabetic neuropathy.

Classification of diabetic neuropathy.

I. Encephalopathy (central neyropathy) is characterized by decreased memory, headache, unadequate actions and others.

II. Peripheral polyneuropathy (radiculoneuropathy). There are three types of radiculoneuropathy:

- distal polyradiculoneuropathy (It is characterized by symmetrical sensory loss, pain at night and during the rest, hyporeflexia, decreased response touch, burning of heels and soles. The skin becomes atrophic, dry and cold, hair loss may be prominent. The decreased response to touch and pain predisposes to burns and ulcers of the legs and toes.);-

- truncal polyradiculoneuropathy (It is an asymmetric, and characterized by pain (which is worse at night), paresthesia and hyperesthesia; muscular weakness involves the muscles of the anterior thigh; reflexes are decreased; weight loss is common.);

- truncal monoradiculoneuropathy (It is usually involves thorasic nerves and the findings are limited to the sensory abnormalities in a radicular distribution.).

III. Visceral dysfunction:

When you want to lift your arm or take a step, your brain sends nerve signals to the appropriate muscles. Internal organs like the heart and bladder are also controlled by nerve signals, but you do not have the same kind of conscious control over them as you do over your arms and legs. The nerves that control your internal organs are called autonomic nerves, and they signal your body to digest food and circulate blood without your having to think about it. Your body's response to sexual stimuli is also involuntary, governed by autonomic nerve signals that increase blood flow to the genitals and cause smooth muscle tissue to relax. Damage to these autonomic nerves is what can hinder normal function.

1) gastrointestinal tract:

- esophageal neuropathy (It is characterized by segmental distribution with low or absent resting pressure in the low or absent resting pressure in the lower esophageal sphincter and by absence of peristalsis in the body of the esophagus.);

- diabetic gastroparesis (It leads to the irregular food absorption and is characterized by nausea, vomiting, early satiety, bloating and abdomen pain.);

- involvement of the bowel (It is characterized by diarrhea (mostly at nighttime, postural diarrhea), constipation, malabsorption and fecal incontinence;

2) cardiovascular system:

- orthostatic hypotension (It is characterized by dizziness, vertigo, faintness, and syncope upon assumption of the upright posture and is caused by failure of peripheral arteriolar constriction.);

- tachicardia (but it does not occur in response to hypotension because of sympathetic involvement).

3) urinary tract:

- Bladder dysfunction can have a profound effect on quality of life. Diabetes can damage the nerves that control bladder function. Men and women with diabetes commonly have bladder symptoms that may include a feeling of urinary urgency, frequency, getting up at night to urinate often, or leakage of urine (incontinence). These symptoms have been called overactive bladder. Less common but more severe bladder symptoms include difficulty urinating and complete failure to empty (retention). These symptoms are called a neurogenic bladder. Some evidence indicates that this problem occurs in both men and women with diabetes at earlier ages than in those without diabetes.

Neurogenic Bladder

In neurogenic bladder, damage to the nerves that go to your bladder can cause it to release urine when you do not intend to urinate, resulting in leakage. Or damage to nerves may prevent your bladder from releasing urine properly and it may be forced back into the kidneys, causing kidney damage or urinary tract infections.

Neurogenic bladder can be caused by diabetes or other diseases, accidents that damage the nerves, or infections.

Symptoms of neurogenic bladder include

  • urinary tract infections
  • loss of the urge to urinate when the bladder is full
  • leakage of urine
  • inability to empty the bladder

4) sexual disorders:

In Men

Erectile Dysfunction

Estimates of the prevalence of erectile dysfunction in men with diabetes range from 20 to 85 percent. Erectile dysfunction is a consistent inability to have an erection firm enough for sexual intercourse. The condition includes the total inability to have an erection, the inability to sustain an erection, or the occasional inability to have or sustain an erection. A recent study of a clinic population revealed that 5 percent of the men with erectile dysfunction also had undiagnosed diabetes.

Men who have diabetes are three times more likely to have erectile dysfunction as men who do not have diabetes. Among men with erectile dysfunction, those with diabetes are likely to have experienced the problem as much as 10 to 15 years earlier than men without diabetes.

In addition to diabetes, other major causes of erectile dysfunction include high blood pressure, kidney disease, alcoholism, and blood vessel disease. Erectile dysfunction may also occur because of the side effects of medications, psychological factors, smoking, and hormonal deficiencies.

If you experience erectile dysfunction, talking to your doctor about it is the first step in getting help. Your doctor may ask you about your medical history, the type and frequency of your sexual problems, your medications, your smoking and drinking habits, and other health conditions. A physical exam and laboratory tests may help pinpoint causes. Your blood glucose control and hormone levels will be checked. The doctor may also ask you whether you are depressed or have recently experienced upsetting changes in your life. In addition, you may be asked to do a test at home that checks for erections that occur while you sleep.

Retrograde Ejaculation

Retrograde ejaculation is a condition in which part or all of a man's semen goes into the bladder instead of out the penis during ejaculation. Retrograde ejaculation occurs when internal muscles, called sphincters, do not function normally. A sphincter automatically opens or closes a passage in the body. The semen mixes with urine in the bladder and leaves the body during urination, without harming the bladder. A man experiencing retrograde ejaculation may notice that little semen is discharged during ejaculation or may become aware of the condition if fertility problems arise. His urine may appear cloudy; analysis of a urine sample after ejaculation will reveal the presence of semen.

Poor blood glucose control and the resulting nerve damage are associated with retrograde ejaculation. Other causes include prostate surgery or some blood pressure medicines.

Sexual Problems in Women With Diabetes

Decreased Vaginal Lubrication

Nerve damage to cells that line the vagina can result in dryness, which in turn may lead to discomfort during sexual intercourse. Discomfort is likely to decrease sexual response or desire.

Decreased or Absent Sexual Response

Diabetes or other diseases, blood pressure medications, certain prescription and over-the-counter drugs, alcohol abuse, smoking, and psychological factors such as anxiety or depression can all cause sexual problems in women. Gynecologic infections or conditions relating to pregnancy or menopause can also contribute to decreased or absent sexual response.

As many as 35 percent of women with diabetes may experience decreased or absent sexual response. Decreased desire for sex, inability to become or remain aroused, lack of sensation, or inability to reach orgasm can result.

Symptoms include

· decreased or total lack of interest in sexual relations

· decreased or no sensation in the genital area

· constant or occasional inability to reach orgasm

· dryness in the vaginal area, leading to pain or discomfort during sexual relations

Neuropathic arthropathy (Charcot’s joints)

is characterized by painless swelling of the feet without edema or signs of infection. The foot becomes shorter and wider, eversion, external rotation, and flattening of the longitudinal arch. This arthropathy is associated with sensory involvelvement, particularly impairment of afferent pain proprioceptive impulses.

Diabetic foot.

Appearance of diabetic foot is caused by a combination of vascular insufficiency, neuropathy, and infection.

Diabetic foot is divided on:

- ischemic;

- neuropathy;

- mixed.

Treatment of long-term complications

The main principle: adequate metabolic control.

Diabetic retinopathy.

1) careful ophthalmologic examination (at least yearly) by ophthalmologist experienced with diabetes;

2) nonproliferative retinopathy:

- anabolic agents (nerabol 5 mg, nerabolil 1mg/week 1,5 – 2 month, retabolil 1ml/3 weeks 3 – 6 times);

- hypocholesterol agents (lipamid, lovostatin);

- antioxydative therapy (emoxipin, trental);

- vitamins B,A,E,PP;

- anticoagulants;

3) preproliferative or proliferative retinopathy: treatment by photocoagulation.

Diabetic nephropathy.

1) low-protein diet (less than 40 g of protein daily);

2) inhibitors of ACF (renitec);

3) hypotensive therapy;

4) hemodyalisis, kidney’s transplantation.

Diabetic angiopathy of lower extremities.

1) patient education in foot care; early detection of risk factors, ulcers, infections, calluses, exposed nails, diminished pulses, deformities;

2) anticoagulants;

3) preparations for improvement blood circulation.

Diabetic neuropathy.

1) Treatments for neuropathy include preparations of α-lipoid acid (Berlition, Espa – lipon, Tiogama),inhibitors of aldose reductase (sorbinil), multivitamins, phenytoin, carbamazepin (Tegretol),amitriptyline, nootropil, piracetam;

2) physiotherapy (inductotermia, magnitolazerotherapy and others).

3) Specific treatment for few types of visceral neuropathy:

- Treatments for erectile dysfunction caused by nerve damage vary widely and range from oral pills, a vacuum pump, pellets placed in the urethra, and shots directly into the penis, to surgery. All these methods have strengths and drawbacks. Psychotherapy to reduce anxiety or address other issues may be necessary. Surgery to implant a device to aid in erection or to repair arteries is another option.

- Retrograde ejaculation caused by diabetes or surgery may be improved with a medication that improves the muscle tone of the bladder neck. A urologist experienced in infertility treatments may assist with techniques to promote fertility, such as collecting sperm from the urine and then using the sperm for artificial insemination.

- Treatment for neurogenic bladder depends on the specific problem and its cause. If the main problem is retention of urine in the bladder, treatment may involve medication to promote better bladder emptying and behavior changes to promote more efficient urination, called timed urination. Occasionally, people may need to periodically insert a thin tube called a catheter through the urethra into the bladder to drain the urine. Learning how to tell when the bladder is full and how to massage the lower abdomen to fully empty the bladder can help as well. If urinary leakage is the main problem, medications or surgery can help.-

Ischemic

Temperature of the skin: decreased

Color of the skin: pallor or cyanotic

Pulsation on peripheral vessels: decreased or absent

Odema: absent

Sensibility: partly decreased or normal

Ulcers: peripheral (distant)

Gangrene: Dry

Neuropatic

Temperature of the skin: normal

Color of the skin: normal or pink

Pulsation on peripheral vessels: normal

Odema: can be

Sensibility: decreased or absent

Ulcers: under the pressure

Gangrene: moist

Clinical summary about DIabetes Mellitus

TYPE 1, or insulin-dependent DIABETES MELLITUS is characterized by pancreatic islet beta cell destruction and absolute insulinopenia.

These individuals are ketosis prone under basal conditions. The onset of the disease is generally in youth, but it can occur at any age. Patients have dependence on daily insulin administration for survival.

Current formulation of the pathogenesis of type 1 DM includes the following:

1. A genetic predisposition, conferred by diabetogenic genes on the short arm of chromosome C, either as part of it or in close proximity to the major histocompatibility complex (MMHC) region (more than 95 % of type 1 diabetes individuals are HLA DR3, DR4 or DR3/DR4; on the other hand, HLA DR2 confers protection against the development of type 1 DM);

2. Putative environmental triggers (possibly viral infections (Coxsackie B, rubella, mumps) or chemical toxins (nitrosourea compounds)) that in genetically susceptible individuals might play a role in initiating the disease process.

3. An immune mechanism gone awry, either initiation of immune destruction or loss of tolerance, leading to slow, progressive loss of pancreatic islet beta cells and eventual clinical onset of type 1 diabetes.

Stages of type 1 DM development (by Flier, 1986)

I. A genetic predisposition or changes of immunity.

Normal β-cells

II. Putative environmental triggers.

III. Active autoimmune insulinitis with β-cells destruction.

Insulinitis

IV. Progression of autoimmune insulities with destruction of >50 % of β-cells.

V. Development of manifest DM.

VI. Total β-cells destruction.

β-cells destruction

TYPE 2or non-insulin-dependent DIABETES MELLITUS is the most common form of diabetes, accounting for 95 – 90 % of the diabetic population. Most investigators agree that genetic factors underlie NIDDM, but it is probably not caused by defects at a single gene locus. Obesity, diet, physical activity, intrauterine environment, and stress are among the most commonly implicated environmental factors which play a role in the development of the disease. In patients with type 2 DM mostly we can find relative insulin insufficiency (when pancreatic gland secrets insulin but it can have changed structure or weight, or circulating enzymes and antibodies destroy normal insulin, or there are changes of insulin receptors).

Pathogenetic and clinical difference of type 1 and type 2 DM.

Signs

Type 1 DM

1. Age: Young (under 40)

2. Beginning of disease; Acute

3. Duration: Labile

4. Ketosis, ketoacidosis: Often develops

5. Body weight: Decreased or normal

6. Treatment: Insulin, diet

7. Degrees of severity: Middle, hard

8. Season of disease beginning: Frequently autumn-winter period

9. Connection with HBA-system: Present

10. Level of insulin and C-peptide: Decreased or absent

11. Antibodies to β-cells: Present in 80-90% of patients on first week, month

12. Late complications: Microangiopathies

13. Mortality: Less than 10%

14. Spreading: 10-20%

Type 2:

1. Age: middle (above 40)

2. Beginning of disease: Gradual

3. Duration: Stable

4. KEtosis, ketoacidosis: Rarely develops

5. Body weight: Obesity in 80-90% of patients

6. Treatment: Diet, Oral hypoglycemic agents or Insulin

7. Degrees of severity: Mild, middle, hard

8. Season of disease beginning: Absent

9. Connection with HBA-System: Absent

10. Level of Insulin and C-peptide: Frequently normal level.

11. Antibiotics of B-cells: Absent

12. Late complications: Macroangiopathies

13. Mortality: More than 20%

14. Spreading: 80-90%

Etiologic classification of DM (WHO, 1999)

I. Type 1 of DM (destruction of β-cells which mostly leads to absolute insulin insufficiency):

- autoimmune;

- idiopathic.

II. Type 2 of DM (resistance to insulin and relative insulin insufficiency or defect of insulin secretion with or without resistance to insulin).

III. Other specific types:

- genetic defects of β-cells function;

- genetic defects of insulin action;

- pancreatic diseases (chronic pancreatitis; trauma, pancreatectomy; tumor of pancreatic gland; fibrocalculosis; hemochromatosis);

- endocrine disease;

- drug exposures;

- infections and others.

IV. Gestation diabetes.

(Gestation diabetes is defined as hyperglycemia diagnosed for the first time in pregnancy. It occurs in individuals who have an inherited predisposition to develop diabetes and may take the form of either type 1 or type 2 diabetes. Gestation diabetes is associated not only with increased rate of perinatal morbidity and neonatal mortality but also with high incidence of subsequent diabetes in mother. Treatment is with diet modification and insulin. Insulin does not cross placenta while oral hypoglycemic agents cross placenta and therefore contrindicated.)

Stages of DM development

1. Prediabetes (risk factors or predispose factors):

- positive family history of DM;

- persons which were born with weight more than 4,0 kg;

- women in which: = were born children with weight more than 4,0 kg; =had abortions and dead child in anamnesis;

- persons with:

= atherosclerosis, hypertension;

= autoimmune diseases;

= furunculosis;

= rubella, mumps, coxsackie virus, infectious hepatitis, cytomegalovirus, infection mononucleosis.

2. Impaired glucose tolerance (latent DM).

3. Clinical manifestation of DM.

Degrees of severity of DM

1.Mild degree:

1) compensation can be achieved by diet;

2) fast serum glucose is less than 8.4 mmol/l;

3) glucosuria less than 20 gr./l (2 %);

4) proneness to ketosis does not occur; long-term (chronic) complications are rare or only functional stages can be observed.

2.Moderate degree:

1) compensation can be achieved by oral hypoglycemic agents (in patients with type 2 DM) or insulin (in patients with type 1 DM);

2) fast serum glucose is 8.4 to 14.0 mmol/l;

3) glucosuria is 20 to 40 gr./l (2 – 4 %);

4) ketosis can occur; long-term (chronic) complications can be observed (but not last stages).

3.Severe degree:

1) compensation can be achieved by insulin or oral hypoglycemic agents;

2) fast serum glucose is over 14,0 mmol/l;

3) glucosuria is over 40 gr./l (4 %);

4) ketosis is common and last stages of long-term (chronic) complications are present.

Stages of compensations:

1. Compensation.

2. Subcompensation.

3. Decompensation.

Criteria of compensative stage.

1. Patient hasn’t new complains.

2. Fast serum glucose level is normal (but can be under 8.0 mmol/l in patients which haven’t complications and under 11.0 mmol/l in patients with long-term complications).

3. Glucose in urine is absent.

4. Glucose level fluctuation is under 4.4-5.5 mmol/l during the day .

5. Comatose and precomatose status are absent.

6. HbA1c <7,0 % (DM type 1), <6,5% (DM type 2)

Criteria of subcompensative stage.

1. Patient may have new complains.

2. Fast serum glucose is high.

3. Glucosuria is present.

4. Glucose level fluctuation is over 4.4-5.5 mmol/l during the day.

5. Comatose or precomatose status are absent.

6. HbA1c 7,0 – 7,5 % (DM type 1), 6,5 – 7,0 % (DM type 2)

Criteria of decompensative stage:

1. Comatose or precomatose status are present.

2. HbA1c >7,5 % (DM type 1), >7<0% (DM type 2).

Duration of DM

1. Stabile (glucose level fluctuation is under 4.4-5.5 mmol/l during the day and comatose or precomatose status are absent).

2. Labile(glucose level fluctuation is over 4.4-5.5 mmol/l during the day or comatose and precomatose status are present).

Pathophysiology of DM

Insulin lack

Defective polymorphonuclear function → infection

Hyperglycemia → glucosurea → polyurea → dehydration

Hyperosmolality

Proteolysis → weight loss → muscle wasting → polyphagia

Lipolysis → free fatty acid release → ketosis → acidosis

- polyurea

(once plasma glucose concentration exceeds the renal threshold (about 180 ml/dl or 8 – 9 mmol/l) glucosurea ensues. Osmotic diuresis induced by glucose results in polyurea and subsequent polydipsia);

- polidipsia

(as more water is excreted, the body requires more water intake);

- polyphagia

(this occurs to lack of energy);

- loss of weight

(energy (calories) is lost as glucose in the urine. Loss of water itself also contributes to weight loss. Increased proteolysis with mobilization of aminoacids leads to enhancement of protein catabolism and loss of weight, notably in muscle mass);

- fatigue and weakness

(probably occur as a result of decreased glucose utilization and electrolyte abnormalities);

- acidosis

(develops due to increased lipolysis which cause the release of free fatty acids, which are metabolized to ketones by the liver).

Presenting signs and symptoms of type2 DM include: polyurea, polydipsia, polyphagia; the majority of individuals (80 – 85 %) are obese, but it can also occur in lean persons.

Patients with DM are at risk if developing of chronic degenerative complications.

Physical examination.

Skin

Diabetes can affect every part of the body, including the skin. The skin is a common target of DM As many as one third of people with diabetes will have a skin disorder caused or affected by diabetes at some time in their lives. In fact, such problems are sometimes the first sign that a person has diabetes. Luckily, most skin conditions can be prevented or easily treated if caught early.

Some of these problems are skin conditions anyone can have, but people with diabetes get more easily. These include bacterial infections, fungal infections, and itching. Other skin problems happen mostly or only to people with diabetes. These include diabetic dermopathy, necrobiosis lipoidica diabeticorum, diabetic blisters, and eruptive xanthomatosis.

Bacterial Infections

Several kinds of bacterial infections occur in people with diabetes. One common one are styes. These are infections of the glands of the eyelid. Another kind of infection are boils, or infections of the hair follicles. Carbuncles are deep infections of the skin and the tissue underneath. Infections can also occur around the nails.

Inflamed tissues are usually hot, swollen, red, and painful. Several different organisms can cause infections. The most common ones are the Staphylococcus bacteria, also called staph.

Once, bacterial infections were life threatening, especially for people with diabetes. Today, death is rare, thanks to antibiotics and better methods of blood sugar control.

But even today, people with diabetes have more bacterial infections than other people do.

Fungal Infections

The culprit in fungal infections of people with diabetes is often Candida albicans. This yeast-like fungus can create itchy rashes of moist, red areas surrounded by tiny blisters and scales. These infections often occur in warm, moist folds of the skin. Problem areas are under the breasts, around the nails, between fingers and toes, in the corners of the mouth, under the foreskin (in uncircumcised men), and in the armpits and groin.

Common fungal infections include jock itch, athlete's foot, ringworm (a ring-shaped itchy patch), and vaginal infection that causes itching.

Itching

Localized itching is often caused by diabetes. It can be caused by a yeast infection, dry skin, or poor circulation. When poor circulation is the cause of itching, the itchiest areas may be the lower parts of the legs.

Diabetic Dermopathy

Diabetes can cause changes in the small blood vessels. These changes can cause skin problems called diabetic dermopathy.

Dermopathy often looks like light brown, scaly patches. These patches may be oval or circular. Some people mistake them for age spots. This disorder most often occurs on the front of both legs. But the legs may not be affected to the same degree. The patches do not hurt, open up, or itch.

Necrobiosis Lipoidica Diabeticorum

Another disease that may be caused by changes in the blood vessels is necrobiosis lipoidica diabeticorum (NLD). NLD is similar to diabetic dermopathy. The difference is that the spots are fewer, but larger and deeper.Iit consists of skin necrosis with lipid infiltration and is also characteristically found in the pretibial area. The lesions resemble red plaques with distinct border.s

NLD often starts as a dull red raised area. After a while, it looks like a shiny scar with a violet border. The blood vessels under the skin may become easier to see. Sometimes NLD is itchy and painful. Sometimes the spots crack open.

NLD is a rare condition. Adult women are the most likely to get it. As long as the sores do not break open, you do not need to have it treated. But if you get open sores, see your doctor for treatment.

Atherosclerosis

Thickening of the arteries - atherosclerosis - can affect the skin on the legs. People with diabetes tend to get atherosclerosis at younger ages than other people do.

As atherosclerosis narrows the blood vessels, the skin changes. It becomes hairless, thin, cool, and shiny. The toes become cold. Toenails thicken and discolor. And exercise causes pain in the calf muscles because the muscles are not getting enough oxygen.

Because blood carries the infection-fighting white cells, affected legs heal slowly when the skin in injured. Even minor scrapes can result in open sores that heal slowly.

People with neuropathy are more likely to suffer foot injuries. These occur because the person does not feel pain, heat, cold, or pressure as well. The person can have an injured foot and not know about it. The wound goes uncared for, and so infections develop easily. Atherosclerosis can make things worse. The reduced blood flow can cause the infection to become severe.

Allergic Reactions

Allergic skin reactions can occur in response to medicines, such as insulin or diabetes pills. You should see your doctor if you think you are having a reaction to a medicine. Be on the lookout for rashes, depressions, or bumps at the sites where you inject insulin.

Diabetic Blisters (Bullosis Diabeticorum)

Rarely, people with diabetes erupt in blisters. Diabetic blisters can occur on the backs of fingers, hands, toes, feet, and sometimes, on legs or forearms.

These sores look like burn blisters. They sometimes are large. But they are painless and have no redness around them. They heal by themselves, usually without scars, in about three weeks. They often occur in people who have diabetic neuropathy. The only treatment is to bring blood sugar levels under control.

Eruptive Xanthomatosis

Eruptive xanthomatosis is another condition caused by diabetes that's out of control. It consists of firm, yellow, pea-like enlargements in the skin. Each bump has a red halo and may itch. This condition occurs most often on the backs of hands, feet, arms, legs, elbows, knees and buttocks.

The disorder usually occurs in young men with type 1 diabetes. The person often has high levels of cholesterol and fat (particularly hyperchylomicronemia) in the blood. Like diabetic blisters, these bumps disappear when diabetes control is restored.

Digital Sclerosis

Sometimes, people with diabetes develop tight, thick, waxy skin on the backs of their hands. Sometimes skin on the toes and forehead also becomes thick. The finger joints become stiff and can no longer move the way they should. Rarely, knees, ankles, or elbows also get stiff.

This condition happens to about one third of people who have type 1 diabetes. The only treatment is to bring blood sugar levels under control.

Disseminated Granuloma Annulare

In disseminated granuloma annulare, the person has sharply defined ring-shaped or arc-shaped raised areas on the skin. These rashes occur most often on parts of the body far from the trunk (for example, the fingers or ears). But sometimes the raised areas occur on the trunk. They can be red, red-brown, or skin-colored.

Acanthosis Nigricans

Acanthosis nigricans is a condition in which tan or brown raised areas appear on the sides of the neck, armpits, and groin. Sometimes they also occur on the hands, elbows, and knees.

Acanthosis nigricans usually strikes people who are very overweight. The best treatment is to lose weight. Some creams can help the spots look better.

Subcutaneous adipose tissue

The abdomen type of obesity is common in patients with type 2 DM. Sometimes generalized subcutaneous adipose tissue atrophy can be observed in diabetics.

Bones and Joints

• Osteoporosis, osteoarthropaphy, diabetic chairopathy (decreasing of the movements of joints) can be find in patients with DM also.

Gastrointestinal tract

Paradontosis, gastritis with decreased secretion ability, gastroduodenitis, hepatosis and diarrhea are common in patients with DM.

Cardiovascular system (CVS)

Involvement of CVS, particularly the coronary circulation, is common in patients with DM.

The heart, arteries, arterioles, and capillaries can be affected. Cardiovascular changes tend to occur earlier in patients with DM when compared with individuals of the same age. Several factors play a role in the high incidence of coronary artery disease seen in patients with DM. These include age of the patient, duration and severity of the diabetes, and presence of other risk factors such as hypertension, smoking and hyperlipoproteinemia. It has been suggested that in some patients with DM, involvement of the small vessels of the heart can lead to cardiomyopathy, independent of narrowing of the major coronary arteries. Myocardial infarction is responsible for at least half of deaths in diabetic patients, and mortality rate for the diabetics is higher than that for nondiabetics of the same age who develop this complication.

Hypertension is common in patients with DM, particularly in the presence of renal disease (as a result of atherosclerosis, destruction of juxtaglomerular cells, sympathetic-nervous-system dysfunction and volume expansion).

Atherosclerosis of femoral, popliteal and calf larger arteries may lead to intermittent claudication, cold extremities, numbness, tingling and gangrene.

Respiratory system

Mucomycosis of the nasopharinx, sinusitis, bronchitis, pneumonia, tuberculosis are more common in patients with diabetes than in nondiabetics.

Kidneys and urinary tract

Renal disease include diabetic nephropathy, necrosing renal papillitis, acute tubular necrosis, lupus erythematosus, acute poststreptococcal and membranoproliferative glomerulonephritis, focal glomerulosclerosis, idiopathic membranous nephropathy, nonspecific immune complex glomerulonephritides, infections can occur in any part of the urinary tract. Last are caused when bacteria, usually from the digestive system, reach the urinary tract. If bacteria are growing in the urethra, the infection is called urethritis. The bacteria may travel up the urinary tract and cause a bladder infection, called cystitis. An untreated infection may go farther into the body and causepyelonephritis, a kidney infection. Some people have chronic or recurrent urinary tract infections.

There is thicken of basement membranes and mesangial expansion and Kimmelstiel -Wilson nodule

Symptoms of urinary tract infections may include

  • a frequent urge to urinate
  • pain or burning in the bladder or urethra during urination
  • cloudy or reddish urine
  • fatigue or shakiness
  • in women, pressure above the pubic bone
  • in men, a feeling of fullness in the rectum

Obviously, these abnormalities, with exception of diabetic nephropathy, are not at all peculiar to DM and can be observed in many other conditions.

Eyes

Complications of the eyes include: ceratities, retinatis, chorioretinatis, cataracts. The last one occurs commonly in the patients with long-standing DM and may be related to uncontrolled hyperglycemia (glucose metabolism by the lens does not require the presence of insulin. The epithelial cells of the lens contain the enzyme aldose reductase, which converts glucose into sorbitol. This sugar may be subsequently converted into fructose by sorbitol dehydrogenase. Sorbitol is retained inside the cells because of its difficulty in transversing plasma membranes. The rise in intracellular osmolality leads to increased water uptake and swelling of the lens).

The diagnosis of DM

The diagnosis of DM may be straightforward or very difficult.

(The presence of the marked hyperglycemia, glucosuria, polyuria, polydipsia, polyphagia, lethargy, a tendency to acquire infections, and physical findings consistent with the disease should offer no difficulty in arriving at the correct diagnosis. On the other hand, mild glucose intolerance in the absence of symptoms or physical findings does not necessarily indicate that DM is present.)

THE DIAGNOSIS OF DM INCLUDE:

I. Clinical manifestationsof DM.

II. Laboratory findings.

1) fasting serum glucose (if the value is over 6,7 mmol/l (120 mg/dl) on two or more separate days, the patient probably has DM);

2) the glucose tolerance test (GTT):

If the diagnosis is still in doubt, then perform a GTT.

Conditions for performing an oral GTT have been standardized:

- no special dietary preparation is required for an oral GTT unless the patient has been ingesting <150 gm/day of carbohydrate. Then give 150 – 200 gm carbohydrate daily for 3 days prior to test;

- unrestricted physical activity should proceed the test;

- test is performed in the morning, following overnight fast of 10 to 16 hours;

- subjects should remain seated, without prior coffee or smoking;

- blood for glucose determination is obtained from an antercubital vein before glucose ingestion and every 30 minutes far 2 hours after ingestion ;

- the amount of glucose given is 75 g for adults (100 g pregnant women, and 1,75 g/kg of ideal body weight for children). Patient have to drink glucose dissolved in 250 ml of water;

- the criteria for diagnosing diabetes in pregnant, adults are:

Fasting serum glucose, mmol/l

3,3 – 5,5

2 hours after glucose loading, mmol/l

<7,8

Capillary blood

5,6 – 6,1

Health

7,8 – 11,1

Impaired glucose tolerance

> 6,1

Diabetes mellitus

> 11,1

a) a fasting serum glucose more than 6,1 mmol/l (120 gm/dl);

b) a 2-hour postprandial serum glucose over 11,1 mmol/l (200 gm/dl);

- the criteria for diagnosing of impaired glucose tolerance are:

a) a fasting serum glucose more than 5,5 mmol/l (100 gm/dl);

b) a 2-hour postprandial serum glucose more than 7,8 mmol/l (140 gm/dl) but less than 11,1 mmol/l (200 gm/dl).

The major indication for an oral GTT is to exclude or diagnose DM (mostly 2) in those suspected of having diabetes although fasting or symptomatic hyperglycemia is absent; e.g., in patients with a clinical condition that might be related to undiagnosed DM (e.g., polyneuropathy, retinopathy). Various conditions (other than DM) and drugs can cause abnormalities in the oral GTT. The criteria of DM do not apply to patients treated with drugs that can impair glucose tolerance (e.g., thiazids, glucocorticoids, indometacin, nicotinic acid, oral contraceptives containing synthetic estrogenes) or to patients who develop nausea, sweating, faintness or pallor during the test, or to have infections, hepatic, renal and endocrine disease that impairs glucose tolerance.

3) islet cell antibody levels will be positive prior to any insulin administration in 60 – 80 % of patients with type 1 DM;

4) C-peptide (it is not affected by antibodies to exogenous insulin and is used to distinguish type 1and 2 DM if there is still a need after clinical determination);

5) glucose level in urine;

6) glycohemoglobin (Hb1Ac) (this test is an indicator of blood sugar control during the previous 2-to-3-month period);

7) acetonurea;

8) blood lipids and others.

III. Instrumental investigations usually are used to diagnose chronic complications of DM.

Diabetes treatment and managements

Glibenclamide tablets for treatment of Diabetics (a sulfonilUreas drug)
Glibenclamide tablets for treatment of Diabetics (a sulfonilUreas drug)
Glimepiride, a second generation sulfonilUreas, also used for the treatment of Diabetes.
Glimepiride, a second generation sulfonilUreas, also used for the treatment of Diabetes.
An Insulin Pump
An Insulin Pump
Metformin, a biguanide, mostly used for the treatment of overweight or obese patients with Diabetes.
Metformin, a biguanide, mostly used for the treatment of overweight or obese patients with Diabetes.
The various Insulin drugs
The various Insulin drugs
Exercise therapy should be recommended but based on the patient's ability anhttp://hubpages.com/u/3846871_50.jpgd capacity.
Exercise therapy should be recommended but based on the patient's ability anhttp://hubpages.com/u/3846871_50.jpgd capacity.
Alcohol should be strongly discouraged in Diabetic patients
Alcohol should be strongly discouraged in Diabetic patients

Acknowledgements

Proffesor of Nephrology, Internal medicine department, Ternopil state medical University, Ukraine
Proffesor of Nephrology, Internal medicine department, Ternopil state medical University, Ukraine | Source
Professor of Pharmacology, Pharmacology department Ternopil state Medical University, Ukraine.
Professor of Pharmacology, Pharmacology department Ternopil state Medical University, Ukraine. | Source
Pharmacology department, Ternopil state Medical University, Ukraine
Pharmacology department, Ternopil state Medical University, Ukraine | Source
Pharmacology department, Ternopil state Medical University, Ukraine
Pharmacology department, Ternopil state Medical University, Ukraine | Source
Pharmacology department, Ternopil State Medical University.
Pharmacology department, Ternopil State Medical University. | Source
Endocrinology Department, Ternopil state Medical University
Endocrinology Department, Ternopil state Medical University | Source
Endocrinology department, Ternopil State Medical University
Endocrinology department, Ternopil State Medical University | Source
Biochemistry department, Ternopi State Medical University, Ukraine
Biochemistry department, Ternopi State Medical University, Ukraine | Source

contributors

Dr. Boadi-Danquah Felix
Dr. Boadi-Danquah Felix
Dr. Sam-Adoki Emmanuel
Dr. Sam-Adoki Emmanuel
Dr. Elenga Gift
Dr. Elenga Gift
Dr. Patience Ayuba Gaji
Dr. Patience Ayuba Gaji
Dr. Ojiemu Jephthah
Dr. Ojiemu Jephthah
Dr. Angela Ojiederhie
Dr. Angela Ojiederhie
Dr. Onyekwere Kingsley Chinomso
Dr. Onyekwere Kingsley Chinomso

Detailed treatment

Methods of treatment of Diabetes Mellitus

Diet, Oral hypoglycemic agents or insulin (indications for each vary with the type of Diabetes Mellitus and severity of the disease). Exercise program, physiotherapy (plant’s therapy), Non-traditional methods of treatment and Education of patients.

Education of the patients The first education should be about the nature of the disease, the importance of its control, all aspects of self-management and routine practices to minimize the development or severity of the diabetes complications. Physicians have to educate motivate and monitor progress, the patients must understand the importance of Life-style changing, the nature of diabetes mellitus and importance of metabolic control. The Knowledge about the principles and importance of good nutrition and reasonable exercise program and the principles of adequate foot, dental and skin care by the patient is very essential. Also the patient can know the treatment of Diabetes Mellitus during the periods of illness. The physician has to educate on the techniques of Insulin administration and measurement of Urine and blood glucose level (if taking Insulin); recognition of hypoglycemia, its causes and method of prevention and finally the importance of general and specific measures to minimize in the best possible way diabetic complications and maintenance of good heath overall.

The main principles of diet

• Balanced diet should include physiologic meal components: Carbohydrate comprises 50-60% of total calories; fat-24-25% and protein- 16-15%). Normal calorie diet in patients with type I Diabetes Mellitus (35-50 Kcal/Kg of ideal weight [weight= height-100]) and lowcaloric diet in Obese persons (mostly in patients with type II Diabetes Mellitus (20-25 Kcal/Kg of ideal weight) We try to decrease weight in obese patients on 1-2 Kg/month by such diet.

• Regimen has to consist of 4-6 small feedings a day. The most frequent regimen consists of 4 feedings a day in which: 1. breakfast comprises 30% of total calories 2. dinner- 40% 3. Lunch- 10% 4. supper- 20%. Sometimes patients need second breakfast (when they have a tendency to develop hyperglycemia). In such a case, it comprises 15% of the total calories and we decrease the quantity of calories of the first breakfast and dinner).

• Exclusion of high-Calorie Carbohydrates (sugar, biscuits, white bread, alcohol). Also increasing the quantity of high fiber-containing foods (fruits [exclusion: banana, grapes], vegetables, cereal grams whole grains flours, bran, patients need 40g fibers per day. • Limiting of meat fat, butter margarine in diet decrease red and brown meats, increase poultry and fish, encourage skim milked-based cheeses. Should be used skim or low-fat milk, not more than 2-3 eggs weekly. Finally Alcohol should be avoided as much as possible because it constitutes a source of additional calories it may worsen hyperglycemia and it may potentiate the hypoglycemic effects of Insulin and oral hypoglycemic agents.

Oral hypoglycemic agents

• Inadequate control of hyperglycemia by the diet and exercises interventions suggests the need for a good glucose-lowering agent.

• Oral hypoglycemic agents are useful only in the chronic management of patients with type II Diabetes Mellitus.

• The most commonly used are: 1. The sulfanilureas 2. The Biguanides 3. Alpha-glucosidase inhibitors, 4. Non-sulfanylureas Insulin stimulators (glinides) 5. Thiosolidinediones (glitazones) 6.

SulfanilUreas Include:

• 1st generation: Tolbutamide, chloripropamide, Tolazemide, Acetohexamide (now are not used in treatment of diabetes)

• 2nd generation: Gilbenclamide (Maninil [3.5mg, 5mg] Daonil [5mg]). Gliquidon (Glurenorm (0.03); Minidiab (5mg); GLiclazide (Diamicron [0.008]; Glipizide; • 3rd generation: Glimepiride (Amaryl (1mg, 2mg).

commonly used Sulphonylureas

The second generation drugs are commonly used such as: Glibenclamid (Maninil, Euglucan, Daonil, Glonil, Gilamat, Gliben, Glucoven). Gliquidon (Glurenorm, Beglicor) are without hepato and nephrotoxic effects, metabolism through the intestine. Also Gliclazid (Diamicron, DIabeton, predian, GLizid) DIabeton normalizes microcirculation and blood aggregation. Finally, the third generation drugs eg, GLimepirin (Amanyl) are used.

Action of Sulfanilureas

It has influence on the Pancreatic gland by increasing the B-cells sensitivity to glucose and as a result, higher secretion of Insulin and also the stimulation of the exocytosis of Insulin by insulocytes. Its non-pancreatic influences are: Increasing the number of receptors to Insulin, normalization of receptors’ sensitivity to Insulin, Increasing of glucose transportation inside muscle cells, stimulation of glycogen synthesis, decreasing of glycogenolysis and glyconeogenesis. It also decreases glucagons secretion.

Indications and contra-indications to Sulfanilureas Usage Indicated for patients with type II Diabetis Mellitus (Over the age of 35-50 years) who do not suffer severe metabolic abnormalities (hyperglycemia) ketosis or hyperosmolality and its good for those with duration of Diabetes of less than 15 years. It is contraindicated in Type I Diabetes Mellitus, Blood diseases, acute infections, heart, cerebral diseases, trauman, pregnant diabetes or lactation, III to IV stages of angiopathy (but Glurenorm can be used in patients with chronic renal failure, because of gastrointestinal tract excretion); then also contra-indicated in Coma and Pre-coma.

commonly used biguanides

• Metformin (dianormet siofor Metforgamma, Metfodar) Glucophage Forte, Metformin 0.25-0.5 in 1 tablet while Glucophage Forte is 0.85 in 1 Tablet, taken 0.5-1.5; 8-10 hours of action and 0.5-2.0; 12-14 hours of duration of action.

• Buformin (Adebit) 0.05 in 1 tablet. Daily dose is 0.1-0.2, 8-10 hours of action. Buformin, Refard; 0.17; daily dose is 0.17- 0.34, 12- 14 hours of action.

Action of biguanides Inhibition of gastro-intestinal glucose absorption, decreasing of glyconeogenesis, Lipogenesis; enhancing glucose transport into muscle cells; Increasing the quantity of insulin’s receptors; stimulation of anaerobic and partly aerobic glycolis and anorrhexogenic effects.

Indications and contra-indications of biguanides Usage Obese patients with type II Diabetes Mellitus, with middle severity of the disease without ketosis. They can be used with the combination of sulfanilureas when sulfonylureas alone have proven inadequate to treat Diabetes Mellitus. Contra-Indications of biguanides usage are; Type I Diabetes Mellitus; heart and Lung disease with their insufficiency 9Chronic heart and Lung faialure); Status with hypoxemia, acute and chronic liver and Kidney diseases with decreased function; Pregnant diabetes, lactation, Old age, alcoholism; Coma and Pre-coma.

Side Effects 1. Allergy 2. Gastro-Intestinal tract disorders 3. Lacto-acidosis.

Alpha-glucosidase Inhibitors

• Acarbosa (Glucobay, Glucor, prandase, precose)- 0.05-0.7, in 1 tablet; daily dose of 0.15-0.6 and a duration of action of 2.7-9.6.

• Miglitol (0.025; 0.05; 0.7 dose in 1 tablet); 0.05-0.3 daily, 2-4hrs of action. • Guar Gum (Guarem)- 5.0 granules, 15-30 daily dosage.

Action of alpha-glucosidase Inhibitors Inhibition of gastro-intestinal tract absorptions (blocation of alpha-glucosidase). Lowering of post prandial glucose level (Postprandial “spikes’ in blood glucose are increasingly implicated as a major cause of Cardiovascular complications); Partly reducing fasting glucose levels by indirectly stimulating insulin secretion in patients who retain B-cells function (and acarbose has a protective effect on B-cells).

Indications and Contra-Indications to alpha-glucosidase Inhibitors Usage Diabetes Mellitus Type II with or without obesity when diet and exercises are not effective. Diabetes mellitus significant violations of glycaemia during a day; secondary sulfanilureas failure; Insulin resistance, Allergic reactions to other hypoglycemic drugs and Hypercholesterolemia. It is contra-indicated in Type I Diabetes Mellitus; Chronic gastro-Intestinal disorders: Pancreatitis, Colitis, Hepatitis. Side effects are flatulence, abdominal bloating, diarrhea.

Non-sulfanylUreas Insulin-Stimulators

Repaglinid (Novonorm, Reglid; meglitinide analogs); 0.00l-0.004, dose in 1 tablet, 0.004-0.009, daily dosage for 3-4 hours. Nateglinid (starlix) (D-Phenilalanine-derivatives); 0.006-0.18 dosage in 1 tablet of 0.18-0.54 daily dose of 1.5- 3 hours duration.

Action of non-SulfanylUreas Insulin Stimulator Stimulation of Insulin production at meal times; Very rapid absorption from the intestine and metabolizing in the liver; (plasma half-life is less than 1 hour).

Indications and contra-Indications to non-sulfanylUreas Insulin stimulator Can be used in elderly with Type II Diabetes Mellitus (due to short half-life) and in renal impairment (because it is metabolized in liver). SulfanylUreas Insulin stimulators are contraindicated in hypoglycemia, transient elevation of Liver enzymes rash and visual disturbances.

commonly used thiozolidinedones

Rosiglitazour (Avandia, roglit, Rosinorm; 0.002-0.008 dose in 1 tablet, of 0.004-0.008 daily dosage. Also, Proglitazone (Actos, Pionorm) of 0.0015-0.045 dose in 1 tablet of 0.015-0.3 daily dosage. Both are active for 24 hours.

Action of thiozolidindiones Agonist to the receptors of the nucleus PPARY of the fat, muscle tissues and the liver. Also increasing of the glucose passage to these tissues; Increasing of Insulin synthesis in the B-cells, increasing of the insulin amount; increasing of glycogen synthesis in the Liver, decreasing of gluconeogenesis and Decreasing of triglycerides.

Indications and contra-indications to thiozolidindiones Usage Diabetes Mellitus Type II, when diet and exercises are no effective; using with sulfanilUreas, biguanides in case of their insufficient efficacy. However, at present, only pioglitazone is approved for use in combination with Insulin. Contra-indications are Diabetic Coma, Pre-coma, Keto-acidosis, Acute and Chronic diseases of the Liver, Heart failure, Pregnancy, lactation, children, teenagers, Allergic reactions to the drug. Side effects are as follows; • Hypoglycemic conditions (rarely) • Peripheral edema • Anemia • Obesity • Elevations of Liver enzymes

Combined preparations Gilbomet consists of Maninil 2.5mg and siofor 400mg. Avandamet consists of Rosiglitazone maleat 2mg and Metformin 200mg.

Insulin Therapy

In 1921, Banting and Best extracted Insulin from Pancreatic gland of newborn Cow. In 1955, Sanger established molecular structure of Insulin and in 1964, Katsoyanis (USA), and Tzan (1965, Germany) synthesized human Insulin.

Indications The following are indications of Insulin: All patients with Type I Diabetes Mellitus; some patients with Type II Diabetes mellitus, Uncontrolled diabetes by diet or oral hypoglycemic agents, Ketoacidosis, Coma, Acute and Chronic Liver and Kidneys disease with decreased function, Pregnancy and lactation, II to IV stages of angiopathy, Infectious diseases, Acute heart and cerebral diseases and surgery.

Insulin preparations

Insulin preparations of Ultrashort action (human analog, recombinant) 1. Novo Rapid (Novo-Nordisk) 2. Humalog (lilly) 3. Epaidia All beginning for 2-10 minutes, maximum action by 40-50 minutes, then total duration of action is between 3 to 5 hours. Insulin preparations of short action 1. Monodar (Indar) 2. Monodar R 3. Monodar RR 4. Monodar R100 5. MonodarR100R 6. Farmasulin HN 7. Actrapid (MCHM) (Novo-Nordisk) For all, beginning of action is between 1 to 3 hours and duration of action lasts for 5-8 hours.

Insulin preparations of intermediate action 1. Monodar B (Indar) 2. Humodar B (Indar) 3. Farmasulin H NP (Farmak) 4. Protaphan (MC, HM) Novo-Nordisk. 5. Insuman basal Aventis 6. Humulin NPH Lilly 7. Monotard HM Novo-Nordisk Action • Beginning of action is between 1-1.5hours • Maximum action is between 6 to 8 hours • Duration of action is between 12 to 18 hours.

Insulin preparations of Long Action Examples are Farmasulin HL (Farmak); Ultralente Humulin (lilly); Ultratard HM, MC suinsulin Ultralong (Indar); Glargine (Lantus-Aventis); Detemir, Levemir. Action • Beginning of action is between 3 to 4 hours • Maximum action takes place between 10 to 12 hours • Duration of action is between 24 hours to 30 hours

Combined Insulin Preparations Insumani comb 25/75 (Aventis). Its beginning of action is 30 minutes, maximum action is 1.5 to 2 hours and then its duration of action is 12-18 hours. Mixtard 30 HM (Novo-Nordisk). Its beginning of action is 30-40 minutes; and maximum action is 1.5-3 hours. Its duration of action is 12- 48 hours. Monodar K30 (Indar). Its beginning of action is 30-40 minutes, its maximum action is 1-3 hours and its duration of action is 12- 16 hours. Monodar K50 (Indar). Beginning of action- 30 minutes, maximum action- 1-3 hours and Durations of action is 6-10 hours. Humodar K15 (Indar). Beginning of action is 30-45 minutes, maximum action is for 1.5 to 3 hours and then Duration of action is 12-18 hours. Humodar K25 (Indar). Beginning of action is 30-40 minutes; maximum action is 1.5-3hours, then duration of action is 12-18 hours. Humodar K50 (Indar); Beginning of action is 30 minutes, maximum action is 1-3 hours and then duration of action is 6- 10 hours.

Initiation and modification of Insulin therapy

It is started as soon as possible in an attempt to “rest” the damaged islet cells and help to “Induce” a remission (“honeymoon” phase). The daily Insulin requirement in patients: On the first year of the disease is 0.3- 0.5 unit of Insulin per Kg of body weight (0.5- if the patient with Ketosis or DKA). On the next years is 0.6- 0.8-1.0 unite/Kg of body weight.

1 Unite

It is activity of 0.04082mg of crystalic insulin (standart). We can use traditional or multiple component insulin program. The last is better. Advantages include the following: • Hypoglycemic reactions may be decreased or prevented because smaller doses of Insulin are needed; • More physiologic match of Insulin to meals is achieved • It uses three or four shots of short-acting insulin (1/3 of total daily dose) Plus intermediate- acting (2/3 of total daily dose) Insulin daily. • 2/3 of the total daily dose we give before breakfast, 1/3 in the evening and then make correction due to the glucose blood level. Insulin doses should be given 30 minutes before meals to allow for adequate absorption of regular Insulin.

Other commonly used Insulin treatment algorithms

• Single pre-breakfast injection of intermediate-acting insulin.

• Intermediate-acting Insulin: pre-breakfast injection of 2/3 total daily dose, 1/3 of daily dose before dinner.

• Combination of intermediate- and short-acting Insulin

• Single pre-breakfast injection of 2/3 intermediate-acting + 1/3 of short-acting

• 2/3- before breakfast, 1/3-before dinner; 2/3-intermediate-acting, ½-short-acting.

• Short-acting Insulin, ½ hour before each meal and a small dose of intermediate-acting Insulin at bedtime.

• Combination of long-acting (in pre-breakfast time) and short-acting Insulin (1/2 hour before each meal).

some peculiarities of Insulin therapy

• Insulin acts faster when is administered intravenously.

• Subcutaneous and intramuscular absorption of Insulin is decreased in the dehydrated or hypotensive patients;

• It is necessary to change the Insulinn injection site (because the absorption is more rapid from the new sites);

• The most rapid absorption from the abdomen

• Exercise accelerates Insulin absorption (before planned exercise program patient has to decrease Insulin dose or take more caloric diet).

Future directions in improving glycemic control

• Nasal Insulin preparations

• Pancreatic transplantation

• Islet replacement therapy

• Genetically engineered pseudo-beta cells.

• Islet cell transplant is the process whereby Islet cells are transplanted from a healthy donor pancreas to a person with Type I diabetes, where they begin producing Insulin.

Side effects and complications of Insulin Therapy

1. Hypoglycemia This complication represents Insulin excess and it can occur at any time (frequently at night). Common symptoms are: early-morning headaches. Precipitating factors are: Irregular ingesting of food’ extreme activity, alcohol interaction, Liver or renal disease; hypopituitarism, adrenal insufficiency etc. It can be treated by preventing coma in such ways:

• Eat Candy or drink sweet orange juice (when the symptoms develop) • Receive intravenous glucose

• 1mg of glucagons administered subcutaneously

• Gradual reduction of Insulin dose in future. Hypoglycemia is a syndrome characterized by sympathetic nervous system and the Stimulation of central nervous system dysfunction that are provoked by an abnormally low-plasma glucose level. Hypoglycemia represents Insulin excess and it can occur at any time. Clinical presentations are as follows: Adrenergic symptoms which are attributed to increased sympathetic activity and epinephrine release. Such symptoms are:

• Sweating

• Nervousness

• Faintness

• Palpitation

• Sometimes hunger

• Impaired vision

• Dizziness

• Fast heartbeat

• Shaking

• Anxiety

• Irritabilityweakness/fatigue The second set of clinical presentations is the Cerebral nervous system manifestations: Confusion inappropriate behavior (which can be mistaken for inebriation); Visual disturbances, stupor, Coma or seizures. (Improvement in the cerebral nervous system manifestations will be with a rise in blood glucose). A common symptom of hypoglycemia is the early morning headache, which is usually present when the patient wakes up. Patients should be familiar with the symptoms of the hypoglycemia but some of them are not heralded by symptoms.

Physical examination

1. The skin is cold, moist

2. Hyper-reflexia can be elicited

3. Hypoglycemic coma is commonly associated with abnormally low body temperatre

4. Patient may be unconscious

5. Laboratory finding shows a very low level of blood glucose Clinical treatment Insulin-treated patients are advised to carry sugar lumps, candy, or glucose tablets at all time. If the symptoms of hypoglycemia develops, the patients have to drink a glass of fruit juice or water with 3 tablespoon of table sugar addd or eat Candy, and to teach their family members to give such treatment if they suddenly exhibit confusion or inappropriate behavior. Another treatment alternative is GLucagon, 0.5- 1Unit (0.5-1ml) Subcutaneous, intramuscular or intravenous. If the patient does not respond to 1 unit of glucagons within 25 minutes,, further injections are unlikely to be effective, and are not recommended. Another alternative also can be an intravenous injection of 20 or 100ml of 40% glucose (10% glucose may be needed) until it clearly can be stopped safely. Finally, Glucocorticoids and adrenaline are helpful as well.

2. Somogyi effect (Somogyi phenomenon, rebound effect)

It is caused by over-insulinazation: hyperglycemia, proceeded by insulin-induced hypoglycemia. Hypoglycemia causes an increase in the secreation of the counter regulatory hormones (glucagons, epinephrine, Cortisol, growth hormone), which inhibit Insulin Secretion and increase glucose output by the liver (as a result of the stimulation of glucogenolysis and glycogenesis). It is treated by the gradual reduction of Insulin dose.

3. Dawn Phenomenon

Many patients with Type I Diabetes demonstrate an early morning (4-8 am) rise in glucose levels, because of activation of counterregulatory hormones. It may be cnfused with the somogyi phenomenon. Sampling of glucose levels throughtout the night might help differentiate the two conditions. Its treatment is by an earlier injection in the morning (5-6 am) and most suggest a late evening )before bedtime) injection of intermediate acting Insulin.

4. Allergic reactions

These include burning and itching at the site of insulin injection’ skin rash, vasculaties, Purpura and anaphylactic reaction. It is treated by the following ways: • Antibistamines • Changing of standard Insulin to pure pork Insulin or to human Insulin • In extreme cases-glucocorticoids.

5. Insulin resistance

Clinical status characterized by Insulin resistance are:

1. Obesity

2. therapy with oral contraceptives

3. glucocorticoid therapy

4. acromegaly

5. cushing’s syndrome

6. acanthosis nigricans

7. chronic liver or renal resistance

8. Non-true insulin resistance maybe caused by long-time injections of Insulin into the one site.

6. Lipodystrophy

It is atrophy or hypertrophy of the adipose-tissue which occur at the site of Insulin Injection. Changing the site of injection and the usage of Human Insulin are the basic treatment strategies of Lipodystrophy

Exercise program

• Exercise is an excellent adjunct to diet therapy, but it is very ineffective when used as the sole weight-reducing modality.

• Exercises must be clearly planned and depend on patient’s ability and the physical conditions exclusion of the competition’s elements.

• Exercises may be valuable adjunct to the management of the Diabetes Mellitus by:

1. Lowering blood glucose concentration

2. decreasing insulin requirements

3. Potentiation of the beneficial effects of diets and other therapy

4. To prevent hypoglycemia, patients should carefully monitor glucose level and taking of Insulin. Mostly they need to reduce the Insulin dosage by 20-25% on the day that strenuous exercises is planned.

Plant therapy (Phytotherapy)

• Hypoglycemic action

• Treatment of chronic diabetes complications

• Influence on the immune reactivity.

Skin

The skin is dry and itchy. There would be infection of the skin by bacteria and fungi, candidiasis of external female genitalia, hyper-keratosis, nail disorders are common in the patients with Diabetes Mellitus but nothing is specific with regard to their development. The most common skin lesion is, diabetic dermopathy (it is characterized by brown, atropic, well-demarcated areas in the pre-tibial region which resemble sears), besides patients sometimes have Xanthoma diabeticorum, which is usually located on the buttocks, elbows and knees, looking like eruptions.

Diabetic retinopathy

Stage I: Background retinopathy is usually the earliest sign and consists of retinal microaneurysms, hard and soft exudates.

Bones and Joints

Osteoporosis and Osteoarthropathy can be found in patients with Diabetes Mellitus also. Diabetes Chairopathy (decreasing of the movements of Joints) could also be another sign. Stage I: Maculopathy or pre-poliferative retinopathy is characterized by macular edemas and or hemorrhages. Stage II: the hallmark of proliferative retinopathy is neurovascularization, i.e growth of new vessels in areas of hypoperfusion. Adhesion of the vessels to the vitreous leads to retinal detachment vitreous hemorrhage and others. The prognosis is extremely poor. 5 years after recognition of this complication 50% of the patients are blind.

ACKNOWLEDGEMENTS

1. Proff Smiyan Svetlana (the Professor and head of Nephronology department for foreign students, Ternopil Medical Univeristy- Ukraine.

2. Dr, Lepyavkon A. Andreivich (MD.)- Department of Internal Medicine (Endocrinology and Pulmonology branch), Ternopil Medical University-Ukraine

3. Dr. Sofia Gusak (MD).- Department of Internal Medicine (Endocrinology branch), Ternopil Medical University-Ukraine.

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Comments 41 comments

D.Virtual.Doctor profile image

D.Virtual.Doctor 6 years ago from Europe Author

So guys! You are welcome to my Endocrinology ward and the first disease I am treating here in my internet hospital. Please leave your comments and ask your questions. I hope to be of good help to you...

Have fun and learn as well.


prettydarkhorse profile image

prettydarkhorse 6 years ago from US

extensive hub about diabetes, complete, Maita


al_masculine 6 years ago

This is a qualitative hub. Now I see why you cal it an internet hospital... Hmm, great!


Dchosen_01 6 years ago

its really an extensive and detailed clinical highlight as you put it. Thanks doc....


D.Virtual.Doctor profile image

D.Virtual.Doctor 6 years ago from Europe Author

thanks dude. lol!


2besure profile image

2besure 6 years ago from Charlotte, North Carolina

Excellent hub on diabetics. It is a tremendously important subject. I had two family member die of it in the same month. Well done!


What can be done to slow diabetes complications? 6 years ago

Findings from the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) have clearly shown that aggressive and intensive control of elevated levels of blood sugar in patients with type 1 and type 2 diabetes decreases the complications of nephropathy, neuropathy, retinopathy, and may reduce the occurrence and severity of large blood vessel diseases. Aggressive control with intensive therapy means achieving fasting glucose levels between 70-120 mg/dl; glucose levels of less than 160 mg/dl after meals; and a near normal hemoglobin A1C levels (see below).

Studies in type 1 patients have shown that in intensively treated patients, diabetic eye disease decreased by 76%, kidney disease decreased by 54%, and nerve disease decreased by 60%. More recently the EDIC trial has shown that type 1 diabetes is also associated with increased heart disease, similar to type 2 diabetes. However, the price for aggressive blood sugar control is a two to three fold increase in the incidence of abnormally low blood sugar levels (caused by the diabetes medications). For this reason, tight control of diabetes to achieve glucose levels between 70-120 mg/dl is not recommended for children under 13 years of age, patients with severe recurrent hypoglycemia, patients unaware of their hypoglycemia, and patients with far advanced diabetes complications. To achieve optimal glucose control without an undue risk of abnormally lowering blood sugar levels, patients with type 1 diabetes must monitor their blood glucose at least four times a day and administer insulin at least three times per day. In patients with type 2 diabetes, aggressive blood sugar control has similar beneficial effects on the eyes, kidneys, nerves and blood vessels.

This is truly a great Hub. You are still in the medical school? Now I see how fresh and informing this hub is, because your head is still very fresh about this topic. I would not be surprised if you just published this after studying the disease. Good work, I must say and keep it up!


Metformin 6 years ago

Metformin is an oral diabetes medicine that helps control blood sugar levels.

Metformin is for people with type 2 (non-insulin-dependent) diabetes. Metformin is sometimes used in combination with insulin or other medications, but it is not for treating type 1 diabetes.

Metformin may also be used for purposes not listed in this medication guide.

Important information about metformin

You should not use this medication if you are allergic to metformin, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin).

If you need to have any type of x-ray or CT scan using a dye that is injected into your veins, you will need to temporarily stop taking metformin.

Before taking metformin, tell your doctor if you have liver disease or a history of heart disease.

Some people develop lactic acidosis while taking metformin. Early symptoms may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, slow or uneven heart rate, dizziness, or feeling very weak or tired.

Before taking metformin

Some people develop a life-threatening condition called lactic acidosis while taking metformin. You may be more likely to develop lactic acidosis if you have liver or kidney disease, congestive heart failure, a severe infection, if you are dehydrated, or if you drink large amounts of alcohol. Talk with your doctor about your individual risk.

You should not use this medication if you are allergic to metformin, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin).

If you need to have any type of x-ray or CT scan using a dye that is injected into your veins, you will need to temporarily stop taking metformin.

To make sure you can safely take metformin, tell your doctor if you have any of these other conditions:

liver disease; or

a history of heart disease.

FDA pregnancy category B. Metformin is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether metformin passes into breast milk or if it could harm a nursing baby. Do not take metformin without first talking to your doctor if you are breast-feeding a baby. Metformin should not be given to a child younger than 10 years old. Extended-release metformin (Glucophage XR) should not be given to a child younger than 17 years old.


Metformin Oral warnings 6 years ago

can rarely cause a serious (sometimes fatal) condition called lactic acidosis. Stop taking metformin and seek immediate medical attention if you develop any of the following symptoms of lactic acidosis: unusual tiredness, severe drowsiness, chills, blue/cold skin, muscle pain, fast/difficult breathing, unusually slow/irregular heartbeat.

Lactic acidosis is more likely to occur in patients who have certain medical conditions, including kidney or liver disease, conditions that may cause a low oxygen blood level or poor circulation (e.g., severe congestive heart failure, recent heart attack, recent stroke), heavy alcohol use, a severe loss of body fluids (dehydration), X-ray or scanning procedures that require an injectable iodinated contrast drug, recent surgery, or a serious infection. Tell your doctor immediately if any of these conditions occur or if you notice a big change in your overall health. You may need to stop taking metformin temporarily. The elderly are also at higher risk, especially those older than 80 years who have not had kidney tests. (See also Side Effects and Precautions sections.)


SulforUreas 6 years ago

If the beta cells are able to produce insulin, this production can be increased by stimulating beta cells with certain medications such as the sulfonylureas and rapid insulin releasers (Prandin and Starlix). Insulin from the beta cells is released directly to the liver via the portal vein, allowing it to work more effectively.

Sulfonylureas can cause low blood sugars, although this occurs much less often than with insulin. Severe low blood sugars occur about 500 times more often with insulin than with sulfonylureas. Emergency room visits for low blood sugars occurred only once for every 4,000 person-years of sulfonylurea use during a large 10 year study done in Switzerland between 1975 and 1984. Low blood sugars brought on by sulfonylureas are generally infrequent and mild.

The original "first generation" sulfonylureas include Orinase (tolbutamide), Tolinase (tolazamide), and Diabinese (chlorpropamide). These drugs work well in lowering the blood sugar, but they have a major drawback. Because they bind to proteins in the blood, they can be dislodged by other medications that bind to these same proteins. Once dislodged, their activity can increase rapidly and lead to low blood sugars.

Diabinese lasts longer in the blood and on rare occasions can cause a severe and long-lasting form of hypoglycemia. Its use was phased out as newer, safer sulfonylureas became available. However, chlorpropamide, the generic form of Diabinese, can still be encountered in many nonprescription oriental “herb mixtures” that are imported and used as over-the-counter treatments for diabetes within the U.S. The product label is unlikely to list chlorpropamide, so the wise approach is to avoid use of any herb mixtures for diabetes.

Second generation sulfonylureas include Glucotrol (glipizide), as well as Micronase, Diabeta, and Glynase (all contain glyburide). A third generation called Amaryl (glimepiride) is also available. These drugs have an advantage for those who use other medications since they do not bind to carrier proteins in the blood. Because of this, drug interactions that may cause low blood sugars are less likely.

Sulfonylureas work best when taken at the same time each day. Glyburide and glipizide are shorter-acting versions. Glyburide (Micronase and Diabeta), and glipizide (Glucotrol) are usually taken twice a day, half before breakfast and half before dinner. Sustained-release versions called Glynase or Glucotrol XL are also available. Long-lasting versions can be taken once a day instead of twice a day. These medications can be used once a day before the evening meal when a person has high blood sugars at bedtime or before breakfast if care is taken to monitor the daytime blood sugar until the safety of the dose is assured.

As well as stimulating insulin production, Amaryl (glimepiride) may cause a mild reduction in insulin resistance and may be less likely to cause low blood sugars than other sulfonylureas. It is also safer for people who have advanced kidney disease indicated by an elevated creatinine level. Other sulfonylureas are usually not recommended when the creatinine level is elevated. Glimepiride also does not block the normal relaxation of blood vessels and does not affect coronary arteries. These unwanted side effects may occur infrequently with other sulfonylureas.

When starting a sulfonylurea, the risk of a low blood sugar is greatest during the first few days to first four months of use. Be careful during this time and check your blood sugar often when you exercise, increase activity, or skip a meal. Drinking alcohol or taking certain medications like decongestants can also increase the risk of a low. Medications, such as steroids, beta blockers, niacin, and Retin-A may decrease the action of a sulfonylurea and cause the blood sugar to rise.

A Recent Study

A recent study has identified a genetic mutation, called KCNJ11, that prevents insulin producing cells from releasing insulin. Dr. Andrew Hattersley of Peninsula Medical School in Exeter had been studying the genes of patients diagnosed with Type 1 diabetes before the age of six months. The reported occurrence rate of this type of diabetes is about 1 in 500,000 but it may be more.

Usually, when you have an elevated blood sugar from eating, your body closes a channel in the insulin producing cells. This causes potassium to accumulate, which triggers another channel to open and release calcium. When the calcium flows into these cells, insulin is released. With the mutated gene, this potassium channel does not close so insulin is not released like it should be. However, giving a sulfonylurea medication that is normally used for Type 2 diabetes helps correct this defect by closing the potassium channel, stimulating the calcium release and the release of insulin.

For more info, visit: http://www.diabetesnet.com/diabetes_treatments/sul...


Diabetes Monitor 6 years ago

Sulfonylureas are well-established as part of the treatment of type 2 diabetes. They are pills that lower blood sugar.

The sulfonylurea ("SU") pills have been available for many years. They are useful as "monotherapy" (as the only diabetes medication) or in various combinations with other types of diabetes pills, Byetta (exenatide) and/or with insulin ("combination therapy"). There are also new pills that are a combination of two ingredients, one of which is a SU and the other another type of pill, such as metformin or a thiazolidinedione.

The action of all the SU's is the same, to cause insulin release from the beta cells; they may have other effects that help lower the blood sugar. There is no data to suggest that using more than one SU at the same time is of any greater benefit than using one.

The sulfonylureas can cause the blood sugar level to go below normal (hypoglycemia), and therefore are sometimes called "hypoglycemic" drugs. (Other classes of diabetes drugs, such as the thiazolidinediones pioglitazone and rosiglitazone, and the alpha-glucosidase inhibitors such as acarbose, do not lower the blood sugar below the normal range, except when used in combination with pills like the SU's or with insulin therapy.) Side effects other than hypoglycemia are rare. Occasionally, chlorpropamide, and more rarely other sulfonylureas, can interact with alcohol to cause vomiting and flushing.

There are many sulfonylurea pills available. Four, known as "first-generation" drugs, have been in use for many years. Three, called "second-generation" drugs, have been developed more recently. They are sometimes stronger than first-generation drugs, but mainly have fewer side effects. Each type of pill is sold under two names: one is the generic name as listed by the US Food and Drug Administration; the other is the brand name given by the manufacturer. Some pills are available as lower-priced generics, others are only available as the branded version. They are:

First-Generation Agents:

Generic Name: acetohexamide

Brand Name: Dymelor

Generic Name: chlorpropamide

Brand Name: Diabinese

Generic Name: tolazamide

Brand Name: Tolinase

Generic Name: tolbutamide

Brand Name: Orinase

Second-Generation Agents:

Generic Name: glimepiride

Brand Name: Amaryl

Generic Name: glipizide

Brand Names: Glucotrol, Glucotrol XL

Generic Name: glyburide

Brand Names: DiaBeta, Micronase, Glynase

Combination Agents:

Combination of glyburide plus metformin

Brand Name: GlucoVance

Combination of glipizide plus metformin

Brand name: Metaglip

Combination of rosiglitazone plus metformin

Brand name: Avandamet

Combination of rosiglitazone plus Amaryl

Brand name: Avandaryl


Insulin Therapy 6 years ago

When type 2 diabetes is clinically diagnosed, only 50 percent of normal beta-cell function remains. The United Kingdom Prospective Diabetes Study (UKPDS)5 demonstrated that this function continues to deteriorate over time despite treatment with diet, exercise, metformin (Glucophage), sulfonylureas, or insulin. Thiazolidinediones appear to preserve beta-cell function in women who had gestational diabetes, thus potentially preventing or delaying the onset of diabetes.6 However, the ability of these drugs to preserve beta-cell function in patients with type 2 diabetes has not yet been proved.

Beta-cell function cannot be estimated accurately on the basis of endogenous insulin levels because of the pulsatile release pattern and short half-life (six to seven minutes). A more accurate estimate is provided by levels of C-peptide, a byproduct of insulin production with a half-life of 30 minutes. However, a low C-peptide level cannot differentiate nearly extinct beta-cell function from reversible glucose toxicity; thus, its determination rarely changes therapy.

Options

Endogenous insulin release can be stimulated by meglitinides (phase 1) or sulfonylureas (phase 2). Sulfonylureas have a 5 to 10 percent annual failure rate (fasting plasma glucose level greater than 200 mg per dL [11.1 mmol per L]).7

Injectable insulin is categorized as basal or bolus insulin based on the duration of action (Table 18 and Figure 2). Basal insulins include neutral protamine Hagedorn (NPH) or isophane insulin (Novolin N, Humulin N), ultralente (extended insulin zinc suspension), and the insulin analogue glargine (Lantus).9 Bolus or mealtime insulins include regular insulin (Novolin R, Humulin R) and the analogue forms aspart (NovoLog) and lispro (Humalog).10 Premixed formulations incorporate NPH and regular or rapid-acting analogues. Inhaled, transdermal, and oral insulin formulations are in development.


The Insulin 6 years ago

When you have type 1 diabetes, it means your pancreas no longer produces insulin. Insulin is necessary to process the glucose that ends up in your bloodstream as a result of the food you eat. So, since you cannot produce insulin on your own, you must get it from another source. All insulin produced in the United States is genetically engineered to closely replicate the type of insulin your body would normally produce if you did not have diabetes.

How Often is Insulin Injected?

Most people with type 1 diabetes start off with at least two injections a day and may have as many as four or more, depending on your doctor’s assessment of your need. As inconvenient as multiple injections each day may sound, research has shown that more daily insulin doses provide better control of blood glucose. And better glucose control means reducing the risk of short and long-term health complications.

Where Should I Inject My Insulin?

Where you inject your insulin has an effect on how quickly it goes to work in your body. For example, insulin injected into your abdomen works faster than when you inject it into your thigh or buttock. It’s usually preferable to inject the insulin in the same muscle group each time so you can predict speed of delivery. But it is important that you rotate the exact location of the injection to avoid developing lumps under the skin.

Are There Different Types of Insulin?

Fortunately, there are a number of different types of insulin available to fit everyone’s lifestyle. Although there are several variations, the main types of insulin are:

Rapid-acting

Starts to work in about 5 minutes, reaches the peak of effectiveness in about one hour and continues working for up to four hours.

Regular or Short-acting

This type of insulin begins to work in about 30 minutes, reaches the peak of effectiveness anywhere between two and three hours and continues working up to six hours.

Intermediate-acting

Usually begins to work in two to four hours, reaches the peak of effectiveness anywhere between two and three hours and continues working up to six hours.

Long-acting

Usually begins to work in six to ten hours and continues working up to 24 hours.

Is a Shot the Only Way to Take Insulin?

No. You can learn more about the several methods of delivering insulin, such as the use of insulin pumps, by watching this video.

Will I Ever Be Able to Stop Taking Insulin?

Because insulin is necessary to survive, you must continue to take insulin as long as you live or until a cure for diabetes is found. But there are alternative devices for delivery of insulin besides manually using a syringe. There are also a number of research studies being conducted that are searching for ways to deliver insulin without the use of a needle.


Diabetes in India 6 years ago

INSULIN THERAPY

WHILST THE USE OF INSULIN IS MANDATORY IN TYPE I PATIENTS, A JUDICIOUS USE OF INSULIN THERAPY MAY BE NECESSARY FOR OPTIMAL MANAGEMENT IN MANY NON INSULIN DEPDENT DIABETICS !

Non dependence does NOT imply that Type II's may never require insulin in order to obtain optimal control.

At the same time, there is increasing apprehension that raised levels of insulin in the blood may itself contribute to hypertension, lipid abnormalities and atherosclerosis.

In view of this, THE DECISION TO USE INSULIN IN NIDDM SHOULD BE TAKEN AFTER CAREFUL, JUDICIOUS CONSIDERATION.

PATIENTS WHO SHOULD RECEIVE INSULIN

Patients manifesting OHA failure.

Insulin should be considered in diabetics with significant complications like ischemic heart disease, CVA, peripheral artery disease, significant retinopathy, nephropathy and neuropathy, hepatic complications such as viral hepatitis.

Any diabetic with an acute problem like several infection, injury, etc., should receive insulin.

Diabetics with tuberculosis often do better with insulin.

Any Type II patient who manifests ketosis for whatever reason.

Diabetics undergoing most surgical procedures, especially those requiring general anesthesia, and where the patient will be on intravenous fluids for any significant period of time should be stabilised on insulin.

Pregnant diabetics, if not "tightly" controlled with diet alone, must be managed with insulin.

Any patient, even if optimally controlled with OHA's who shows evidence that may contraindicate the use of these oral agents, must be shifted to insulin.

Many underweight patients and those with significant symptoms would do better with insulin therapy, possibly in combination with small doses of sulfonylureas;

TOP

Types of INSULINS available for clinical use:

The insulins available for routine clinical use are the beef, porcine and human insulins.

The insulins available now are the "pure" varieties and contain negligible amounts of contaminants.

Beef insulins differ from human insulin in three amino acids, whilst porcine insulin differs from human insulin in only one amino acid. Thus, porcine amino acids are less immunogenic than beef insulins.

But the beef insulins continue to be widely used in view of their relatively lower costs.

Human insulins are pure and have the same amino acid structure as that of native insulin.

They are made by genetic engineering or by transformation from porcine insulin by substituting alanine with threonine in the B30 position.

Human insulins are replacing the other insulins in most developed countries, but its cost is the inhibiting factor to its widespread acceptability in most developing countries.

PATIENTS WHO SHOULD PREFERABLY USE HUMAN INSULINS are:

All patients who are on beef or porcine insulins and manifest resistance due to the presence of antibodies;

Patients requiring intermittent therapy, i.e. patients with gestational diabetes, those undergoing major surgery, patients with acute infections, etc., who otherwise may be controlled on diet, with or with out OHA's, should use Human insulins.

Patients who require very large doses of beef or porcine insulins (>80 units/day), may benefit with change over to human insulins.


Medscape 6 years ago

January 26, 2010 — Intensive insulin therapy does not show a survival benefit for patients treated with hydrocortisone for septic shock, according to the results of a multicenter, 2 x 2-factorial, randomized controlled trial reported in the January 27 issue of the Journal of the American Medical Association.

"Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock," write Djillali Annane, MD, from the Hôpital Raymond Poincaré in Garches, France, and colleagues from the Corticosteroids and Intensive Insulin Therapy for Septic Shock (COIITSS) trial. "In addition, the benefit of adding fludrocortisone in this setting is unclear."

The main goal of the study was to determine the effectiveness of intensive insulin therapy in patients treated with hydrocortisone for septic shock, and a secondary goal was to evaluate the benefit of fludrocortisone.

From January 2006 to January 2009 at 11 intensive care units in France, 509 adults with septic shock who presented with multiple organ dysfunction, defined by a Sequential Organ Failure Assessment score of 8 or more, and who had received hydrocortisone treatment, were randomly selected to 1 of 4 groups: continuous intravenous insulin infusion with hydrocortisone alone, continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone, conventional insulin therapy with hydrocortisone alone, or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone.

Dosage of hydrocortisone was a 50-mg bolus every 6 hours for 7 days, and fludrocortisone dosage was 50-?g oral tablets once daily for 7 days. The primary study endpoint was in-hospital mortality.

Deaths occurred in 117 (45.9%) of 255 patients treated with intensive insulin and in 109 (42.9%) of 254 patients treated with conventional insulin therapy (relative risk [RR], 1.07; 95% confidence interval [CI], 0.88 - 1.30; P = .50). Compared with patients in the conventional-treatment group, those in the intensive insulin therapy group had significantly more episodes of severe hypoglycemia (< 40 mg/dL). The difference in mean number of episodes per patient was 0.15 (95% CI, 0.02 - 0.28; P = .003).

Secondary outcomes did not differ significantly between treatment groups. These included median number of days spent in the intensive care unit, median length of hospital stay, median vasopressor-free days, and median days free of mechanical ventilation.

Mortality during hospitalization occurred in 105 (42.9%) of 245 patients treated with fludrocortisone and in 121 (45.8%) of 264 patients in the control group (RR, 0.94; 95% CI, 0.77 - 1.14; P = .50).

"Compared with conventional insulin therapy, intensive insulin therapy did not improve in-hospital mortality among patients who were treated with hydrocortisone for septic shock," the study authors write. "The addition of oral fludrocortisone did not result in a statistically significant improvement in in-hospital mortality."

Limitations of this study include inability to exclude the benefit of some glucose control vs no control at all in corticosteroid-treated septic shock.

"The current study showed no evidence to support a strategy of intensive insulin therapy aimed at maintaining blood glucose levels in the range of 80 to 110 mg/dL for treating septic shock with corticosteroids," the study authors conclude. "The current data do not support the routine use of oral fludrocortisone in addition to hydrocortisone when physicians decide to introduce corticosteroids in the management of a patient with septic shock."

In an accompanying editorial, Greet Van den Berghe, MD, PhD, from Catholic University of Leuven in Leuven, Belgium, recommends larger trials of treatment of septic shock.

"To ensure that such studies can be completed in a timely fashion, the cooperation of national and international trials groups, and their funding sources, will likely be necessary," Dr. Van den Berghe writes. "Precedents for large-scale international cooperation exist in oncology and cardiology. Given the huge global burden of conditions such as septic shock, which causes hundreds of thousands of deaths in the United States alone each year, such international collaboration should and must be achievable."


ncbi 6 years ago

Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known.

METHODS: We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter [4.4 and 6.1 mmol per liter]) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter [11.9 mmol per liter] and maintenance of glucose at a level between 180 and 200 mg per deciliter [10.0 and 11.1 mmol per liter]).

RESULTS: At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P


al_masculine 6 years ago

this hospital of yours is really good. I can see how it is taking lots of affiliate. Hmm! Keep it up man...


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CrazyGata 6 years ago from Puerto Rico

Sir, I cannot say I read all of it, but thank you for the contribution, I do need to take a closer look at this.


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D.Virtual.Doctor 6 years ago from Europe Author

Yeah, CrazyGata, its very difficult to read everything, especially if your mind is set to read some interesting and refreshing hubs. Interested people who might read everything may be researchers, medical personnels and/or the main diabetics who are searching the internet to get some answers. But its still good you touched some aspect, that is its essence. Thanks for the comment..


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elayne001 6 years ago from Rocky Mountains

My mother had diabetes and had to take medicine daily. I hope I can avoid it. Thanks for this valuable information.


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earnestshub 6 years ago from Melbourne Australia

Fantastic hub! Diabetes is a huge subject requiring a huge article like this one.

This information is important. I can proudly say that my son got a mention in a diabetes breakthrough in Australia. He is in animal husbandry and provided the animal care and regular injections of mice over the period of the R&D.

My mum was diabetic and in her times needed to take huge doses of insulin.

Very useful and informative hub, thank you.


D.Virtual.Doctor profile image

D.Virtual.Doctor 6 years ago from Europe Author

thanks for the comment earnestshub... From all the comments you see here within a short period of time, you can easily tell of the huge economic importance diabetes mellitus is to us....


HArvard Medical school 6 years ago

What is diabetes?

Diabetes mellitus is a group of metabolic diseases characterized by high blood sugar (glucose) levels, that result from defects in insulin secretion, or action, or both. Diabetes mellitus, commonly referred to as diabetes (as it will be in this article) was first identified as a disease associated with "sweet urine," and excessive muscle loss in the ancient world. Elevated levels of blood glucose (hyperglycemia) lead to spillage of glucose into the urine, hence the term sweet urine.

Normally, blood glucose levels are tightly controlled by insulin, a hormone produced by the pancreas. Insulin lowers the blood glucose level. When the blood glucose elevates (for example, after eating food), insulin is released from the pancreas to normalize the glucose level. In patients with diabetes, the absence or insufficient production of insulin causes hyperglycemia. Diabetes is a chronic medical condition, meaning that although it can be controlled, it lasts a lifetime.


university of pennsylvania school of medicine 6 years ago

What is the impact of diabetes?

Over time, diabetes can lead to blindness, kidney failure, and nerve damage. These types of damage are the result of damage to small vessels, referred to as microvascular disease. Diabetes is also an important factor in accelerating the hardening and narrowing of the arteries (atherosclerosis), leading to strokes, coronary heart disease, and other large blood vessel diseases. This is referred to as macrovascular disease. Diabetes affects approximately 17 million people (about 8% of the population) in the United States. In addition, an estimated additional 12 million people in the United States have diabetes and don't even know it.

From an economic perspective, the total annual cost of diabetes in 1997 was estimated to be 98 billion dollars in the United States. The per capita cost resulting from diabetes in 1997 amounted to $10,071.00; while healthcare costs for people without diabetes incurred a per capita cost of $2,699.00. During this same year, 13.9 million days of hospital stay were attributed to diabetes, while 30.3 million physician office visits were diabetes related. Remember, these numbers reflect only the population in the United States. Globally, the statistics are staggering.

Diabetes is the third leading cause of death in the United States after heart disease and cancer.


johns hopkins university school of medicine 6 years ago

What causes diabetes?

Insufficient production of insulin (either absolutely or relative to the body's needs), production of defective insulin (which is uncommon), or the inability of cells to use insulin properly and efficiently leads to hyperglycemia and diabetes. This latter condition affects mostly the cells of muscle and fat tissues, and results in a condition known as "insulin resistance." This is the primary problem in type 2 diabetes. The absolute lack of insulin, usually secondary to a destructive process affecting the insulin producing beta cells in the pancreas, is the main disorder in type 1 diabetes. In type 2 diabetes, there also is a steady decline of beta cells that adds to the process of elevated blood sugars. Essentially, if someone is resistant to insulin, the body can, to some degree, increase production of insulin and overcome the level of resistance. After time, if production decreases and insulin cannot be released as vigorously, hyperglycemia develops.

Glucose is a simple sugar found in food. Glucose is an essential nutrient that provides energy for the proper functioning of the body cells. Carbohydrates are broken down in the small intestine and the glucose in digested food is then absorbed by the intestinal cells into the bloodstream, and is carried by the bloodstream to all the cells in the body where it is utilized. However, glucose cannot enter the cells alone and needs insulin to aid in its transport into the cells. Without insulin, the cells become starved of glucose energy despite the presence of abundant glucose in the bloodstream. In certain types of diabetes, the cells' inability to utilize glucose gives rise to the ironic situation of "starvation in the midst of plenty". The abundant, unutilized glucose is wastefully excreted in the urine.

Insulin is a hormone that is produced by specialized cells (beta cells) of the pancreas. (The pancreas is a deep-seated organ in the abdomen located behind the stomach.) In addition to helping glucose enter the cells, insulin is also important in tightly regulating the level of glucose in the blood. After a meal, the blood glucose level rises. In response to the increased glucose level, the pancreas normally releases more insulin into the bloodstream to help glucose enter the cells and lower blood glucose levels after a meal. When the blood glucose levels are lowered, the insulin release from the pancreas is turned down. It is important to note that even in the fasting state there is a low steady release of insulin than fluctuates a bit and helps to maintain a steady blood sugar level during fasting. In normal individuals, such a regulatory system helps to keep blood glucose levels in a tightly controlled range. As outlined above, in patients with diabetes, the insulin is either absent, relatively insufficient for the body's needs, or not used properly by the body. All of these factors cause elevated levels of blood glucose (hyperglycemia).


university of california--san francisco school of medicine 6 years ago

What are the different types of diabetes?

There are two major types of diabetes, called type 1 and type 2. Type 1 diabetes was also called insulin dependent diabetes mellitus (IDDM), or juvenile onset diabetes mellitus. In type 1 diabetes, the pancreas undergoes an autoimmune attack by the body itself, and is rendered incapable of making insulin. Abnormal antibodies have been found in the majority of patients with type 1 diabetes. Antibodies are proteins in the blood that are part of the body's immune system. The patient with type 1 diabetes must rely on insulin medication for survival.

In autoimmune diseases, such as type 1 diabetes, the immune system mistakenly manufactures antibodies and inflammatory cells that are directed against and cause damage to patients' own body tissues. In persons with type 1 diabetes, the beta cells of the pancreas, which are responsible for insulin production, are attacked by the misdirected immune system. It is believed that the tendency to develop abnormal antibodies in type 1 diabetes is, in part, genetically inherited, though the details are not fully understood.

Exposure to certain viral infections (mumps and Coxsackie viruses) or other environmental toxins may serve to trigger abnormal antibody responses that cause damage to the pancreas cells where insulin is made. Some of the antibodies seen in type 1 diabetes include anti-islet cell antibodies, anti-insulin antibodies and anti-glutamic decarboxylase antibodies. These antibodies can be measured in the majority of patients, and may help determine which individuals are at risk for developing type 1 diabetes.

At present, the American Diabetes Association does not recommend general screening of the population for type 1 diabetes, though screening of high risk individuals, such as those with a first degree relative (sibling or parent) with type 1 diabetes should be encouraged. Type 1 diabetes tends to occur in young, lean individuals, usually before 30 years of age, however, older patients do present with this form of diabetes on occasion. This subgroup is referred to as latent autoimmune diabetes in adults (LADA). LADA is a slow, progressive form of type 1 diabetes. Of all the patients with diabetes, only approximately 10% of the patients have type 1 diabetes and the remaining 90% have type 2 diabetes.

Type 2 diabetes was also referred to as non-insulin dependent diabetes mellitus (NIDDM), or adult onset diabetes mellitus (AODM). In type 2 diabetes, patients can still produce insulin, but do so relatively inadequately for their body's needs, particularly in the face of insulin resistance as discussed above. In many cases this actually means the pancreas produces larger than normal quantities of insulin. A major feature of type 2 diabetes is a lack of sensitivity to insulin by the cells of the body (particularly fat and muscle cells).

In addition to the problems with an increase in insulin resistance, the release of insulin by the pancreas may also be defective and suboptimal. In fact, there is a known steady decline in beta cell production of insulin in type 2 diabetes that contributes to worsening glucose control. (This is a major factor for many patients with type 2 diabetes who ultimately require insulin therapy.) Finally, the liver in these patients continues to produce glucose through a process called gluconeogenesis despite elevated glucose levels. The control of gluconeogenesis becomes compromised.

While it is said that type 2 diabetes occurs mostly in individuals over 30 years old and the incidence increases with age, we are seeing an alarming number patients with type 2 diabetes who are barely in their teen years. In fact, for the first time in the history of humans, type 2 diabetes is now more common than type 1 diabetes in childhood. Most of these cases are a direct result of poor eating habits, higher body weight, and lack of exercise.

While there is a strong genetic component to developing this form of diabetes, there are other risk factors - the most significant of which is obesity. There is a direct relationship between the degree of obesity and the risk of developing type 2 diabetes, and this holds true in children as well as adults. It is estimated that the chance to develop diabetes doubles for every 20% increase over desirable body weight.

Regarding age, data shows that for each decade after 40 years of age regardless of weight there is an increase in incidence of diabetes. The prevalence of diabetes in persons 65 to 74 years of age is nearly 20%. Type 2 diabetes is also more common in certain ethnic groups. Compared with a 6% prevalence in Caucasians, the prevalence in African Americans and Asian Americans is estimated to be 10%, in Hispanics 15%, and in certain Native American communities 20% to 50%. Finally, diabetes occurs much more frequently in women with a prior history of diabetes that develops during pregnancy (gestational diabetes - see below).

Diabetes can occur temporarily during pregnancy. Significant hormonal changes during pregnancy can lead to blood sugar elevation in genetically predisposed individuals. Blood sugar elevation during pregnancy is called gestational diabetes. Gestational diabetes usually resolves once the baby is born. However, 25%-50% of women with gestational diabetes will eventually develop type 2 diabetes later in life, especially in those who require insulin during pregnancy and those who remain overweight after their delivery. Patients with gestational diabetes are usually asked to undergo an oral glucose tolerance test about six weeks after giving birth to determine if their diabetes has persisted beyond the pregnancy, or if any evidence (such as impaired glucose tolerance) is present that may be a clue to the patient's future risk for developing diabetes.

"Secondary" diabetes refers to elevated blood sugar levels from another medical condition. Secondary diabetes may develop when the pancreatic tissue responsible for the production of insulin is destroyed by disease, such as chronic pancreatitis (inflammation of the pancreas by toxins like excessive alcohol), trauma, or surgical removal of the pancreas.

Diabetes can also result from other hormonal disturbances, such as excessive growth hormone production (acromegaly) and Cushing's syndrome. In acromegaly, a pituitary gland tumor at the base of the brain causes excessive production of growth hormone, leading to hyperglycemia. In Cushing's syndrome, the adrenal glands produce an excess of cortisol, which promotes blood sugar elevation.

In addition, certain medications may worsen diabetes control, or "unmask" latent diabetes. This is seen most commonly when steroid medications (such as prednisone) are taken and also with medications used in the treatment of HIV infection (AIDS).


washington university in st. louis school of medicine 6 years ago

What are diabetes symptoms?

The early symptoms of untreated diabetes are related to elevated blood sugar levels, and loss of glucose in the urine. High amounts of glucose in the urine can cause increased urine output and lead to dehydration. Dehydration causes increased thirst and water consumption.

The inability of insulin to perform normally has effects on protein, fat and carbohydrate metabolism. Insulin is an anabolic hormone, that is, one that encourages storage of fat and protein.

A relative or absolute insulin deficiency eventually leads to weight loss despite an increase in appetite.

Some untreated diabetes patients also complain of fatigue, nausea and vomiting.

Patients with diabetes are prone to developing infections of the bladder, skin, and vaginal areas.

Fluctuations in blood glucose levels can lead to blurred vision. Extremely elevated glucose levels can lead to lethargy and coma.


duke university medical center 6 years ago

How is diabetes diagnosed?

The fasting blood glucose (sugar) test is the preferred way to diagnose diabetes. It is easy to perform and convenient. After the person has fasted overnight (at least 8 hours), a single sample of blood is drawn and sent to the laboratory for analysis. This can also be done accurately in a doctor's office using a glucose meter.

Normal fasting plasma glucose levels are less than 100 milligrams per deciliter (mg/dl).

Fasting plasma glucose levels of more than 126 mg/dl on two or more tests on different days indicate diabetes.

A random blood glucose test can also be used to diagnose diabetes. A blood glucose level of 200 mg/dl or higher indicates diabetes.

When fasting blood glucose stays above 100mg/dl, but in the range of 100-126mg/dl, this is known as impaired fasting glucose (IFG). While patients with IFG do not have the diagnosis of diabetes, this condition carries with it its own risks and concerns, and is addressed elsewhere.


university of michigan--ann arbor medical school 6 years ago

The oral glucose tolerance test

Though not routinely used anymore, the oral glucose tolerance test (OGTT) is a gold standard for making the diagnosis of type 2 diabetes. It is still commonly used for diagnosing gestational diabetes and in conditions of pre-diabetes, such as polycystic ovary syndrome. With an oral glucose tolerance test, the person fasts overnight (at least eight but not more than 16 hours). Then first, the fasting plasma glucose is tested. After this test, the person receives 75 grams of glucose (100 grams for pregnant women). There are several methods employed by obstetricians to do this test, but the one described here is standard. Usually, the glucose is in a sweet-tasting liquid that the person drinks. Blood samples are taken at specific intervals to measure the blood glucose.

For the test to give reliable results:

the person must be in good health (not have any other illnesses, not even a cold).

the person should be normally active (not lying down, for example, as an inpatient in a hospital), and

the person should not be taking medicines that could affect the blood glucose.

For three days before the test, the person should have eaten a diet high in carbohydrates (200-300 grams per day).

The morning of the test, the person should not smoke or drink coffee.

The classic oral glucose tolerance test measures blood glucose levels five times over a period of three hours. Some physicians simply get a baseline blood sample followed by a sample two hours after drinking the glucose solution. In a person without diabetes, the glucose levels rise and then fall quickly. In someone with diabetes, glucose levels rise higher than normal and fail to come back down as fast.

People with glucose levels between normal and diabetic have impaired glucose tolerance (IGT). People with impaired glucose tolerance do not have diabetes, but are at high risk for progressing to diabetes. Each year, 1%-5% of people whose test results show impaired glucose tolerance actually eventually develop diabetes. Weight loss and exercise may help people with impaired glucose tolerance return their glucose levels to normal. In addition, some physicians advocate the use of medications, such as metformin (Glucophage), to help prevent/delay the onset of overt diabetes.

Recent studies have shown that impaired glucose tolerance itself may be a risk factor for the development of heart disease. In the medical community, most physicians are now understanding that impaired glucose tolerance is nor simply a precursor of diabetes, but is its own clinical disease entity that requires treatment and monitoring.


university of washington medical center 6 years ago

Evaluating the results of the oral glucose tolerance test

Glucose tolerance tests may lead to one of the following diagnoses:

Normal response: A person is said to have a normal response when the 2-hour glucose level is less than 140 mg/dl, and all values between 0 and 2 hours are less than 200 mg/dl.

Impaired glucose tolerance: A person is said to have impaired glucose tolerance when the fasting plasma glucose is less than 126 mg/dl and the 2-hour glucose level is between 140 and 199 mg/dl.

Diabetes: A person has diabetes when two diagnostic tests done on different days show that the blood glucose level is high.

Gestational diabetes: A woman has gestational diabetes when she has any two of the following: a 100g OGTT, a fasting plasma glucose of more than 95 mg/dl, a 1-hour glucose level of more than 180 mg/dl, a 2-hour glucose level of more than 155 mg/dl, or a 3-hour glucose level of more than 140 mg/dl.


university of washington medical center 6 years ago

What are diabetes symptoms?

The early symptoms of untreated diabetes are related to elevated blood sugar levels, and loss of glucose in the urine. High amounts of glucose in the urine can cause increased urine output and lead to dehydration. Dehydration causes increased thirst and water consumption.

The inability of insulin to perform normally has effects on protein, fat and carbohydrate metabolism. Insulin is an anabolic hormone, that is, one that encourages storage of fat and protein.

A relative or absolute insulin deficiency eventually leads to weight loss despite an increase in appetite.

Some untreated diabetes patients also complain of fatigue, nausea and vomiting.

Patients with diabetes are prone to developing infections of the bladder, skin, and vaginal areas.

Fluctuations in blood glucose levels can lead to blurred vision. Extremely elevated glucose levels can lead to lethargy and coma.


yale university medical school 6 years ago

How is diabetes diagnosed?

The fasting blood glucose (sugar) test is the preferred way to diagnose diabetes. It is easy to perform and convenient. After the person has fasted overnight (at least 8 hours), a single sample of blood is drawn and sent to the laboratory for analysis. This can also be done accurately in a doctor's office using a glucose meter.

Normal fasting plasma glucose levels are less than 100 milligrams per deciliter (mg/dl).

Fasting plasma glucose levels of more than 126 mg/dl on two or more tests on different days indicate diabetes.

A random blood glucose test can also be used to diagnose diabetes. A blood glucose level of 200 mg/dl or higher indicates diabetes.

When fasting blood glucose stays above 100mg/dl, but in the range of 100-126mg/dl, this is known as impaired fasting glucose (IFG). While patients with IFG do not have the diagnosis of diabetes, this condition carries with it its own risks and concerns, and is addressed elsewhere.


Columbia University medcenter 6 years ago

The oral glucose tolerance test

Though not routinely used anymore, the oral glucose tolerance test (OGTT) is a gold standard for making the diagnosis of type 2 diabetes. It is still commonly used for diagnosing gestational diabetes and in conditions of pre-diabetes, such as polycystic ovary syndrome. With an oral glucose tolerance test, the person fasts overnight (at least eight but not more than 16 hours). Then first, the fasting plasma glucose is tested. After this test, the person receives 75 grams of glucose (100 grams for pregnant women). There are several methods employed by obstetricians to do this test, but the one described here is standard. Usually, the glucose is in a sweet-tasting liquid that the person drinks. Blood samples are taken at specific intervals to measure the blood glucose.

For the test to give reliable results:

the person must be in good health (not have any other illnesses, not even a cold).

the person should be normally active (not lying down, for example, as an inpatient in a hospital), and

the person should not be taking medicines that could affect the blood glucose.

For three days before the test, the person should have eaten a diet high in carbohydrates (200-300 grams per day).

The morning of the test, the person should not smoke or drink coffee.

The classic oral glucose tolerance test measures blood glucose levels five times over a period of three hours. Some physicians simply get a baseline blood sample followed by a sample two hours after drinking the glucose solution. In a person without diabetes, the glucose levels rise and then fall quickly. In someone with diabetes, glucose levels rise higher than normal and fail to come back down as fast.

People with glucose levels between normal and diabetic have impaired glucose tolerance (IGT). People with impaired glucose tolerance do not have diabetes, but are at high risk for progressing to diabetes. Each year, 1%-5% of people whose test results show impaired glucose tolerance actually eventually develop diabetes. Weight loss and exercise may help people with impaired glucose tolerance return their glucose levels to normal. In addition, some physicians advocate the use of medications, such as metformin (Glucophage), to help prevent/delay the onset of overt diabetes.

Recent studies have shown that impaired glucose tolerance itself may be a risk factor for the development of heart disease. In the medical community, most physicians are now understanding that impaired glucose tolerance is nor simply a precursor of diabetes, but is its own clinical disease entity that requires treatment and monitoring.


D.Virtual.Doctor profile image

D.Virtual.Doctor 6 years ago from Europe Author

My lord and my God! What else can I say? Is there anything short or lacking about this Internet Hospital? There is immense growth and I am really proud of it. I just cannot imagine how this place would be in the next 3, 4, 5 and even 20 years. Thanks so much to all the US Med schools and Hospitals who contributed here.


Good Guy profile image

Good Guy 6 years ago from Malaysia

Awesome!! I think this is the looongest hub. Even to scroll down, is such a challenge, let alone reading it.

You are fantastic!

(Vote up and awesome!)


D.Virtual.Doctor profile image

D.Virtual.Doctor 6 years ago from Europe Author

Thanks a lot Good Guy! Yeah, it is challenging reading it because it talks about everything relating to Diabetis Mellitus. Thanks for your comment..


hibblekibble profile image

hibblekibble 6 years ago from USA

Really nice hub, very informational and useful for those who are trying to understand diabetes better.


D.Virtual.Doctor profile image

D.Virtual.Doctor 6 years ago from Europe Author

thanks a lot hibblekibble


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unbeatable stephy 5 years ago

that was great,its really a job well done. I am so impressed, still and will always be proud of you.


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D.Virtual.Doctor 5 years ago from Europe Author

my head is getting larger~~~~~~~~lol!


D.Virtual.Doctor profile image

D.Virtual.Doctor 4 years ago from Europe Author

Thanks a lot

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