Diabetes mellitus is the most common endocrine disorder. It is a disease of modern life. Once it regarded as a single disease entity, but now it is considered as hetrogenous group of disorder. In spite of the best effort from the world of medicine this disease is still baffling the physician. 
Diabetes mellitus is characterized by a state of hyperglycemia which resulting from a diversity of etiologies – environmental and genetic acting jointly. 

Definition:    
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia with or without glycosuria resulting from an absolute or relative deficiency of insulin.
What is insulin?
Insulin is the hypoglycemic, antidiabetic factor and the protein hormone, which regulate the blood glucose, secreted by the b cells of islands of langerhands.

Functions:
On carbohydrate metabolism 
1. Insulin increases the deposition of glucose in the liver and muscle as glycogen. (Glycogen formation and storage) 
2. It also increases the oxidation of glucose to carbon dioxide in the tissues and depresses gluconeogensis (formation of glucose from sources other than carbohydrate.)
On protein metabolism 
  1. Prevent gluconeogensis. 
On fat metabolism 
  1. Prevent formation of keton bodies.  
The underlying cause for the diabetes mellitus is the defective production or action of insulin.
In normal individual about 50 units of insulin are secreted by the pancreas daily.
 
  In conditions of insufficient insulin there are increased gluconeogensis, glycogenolysis, hyperglycemia, hyperosmolalaemia, ketogensis, polyurea and etc 
Insufficient insulin ® } Hyperlipolysis ® Ketoacidosis ® Ketonuria . Hyperglyconeogenesis,Hyperglycemia ® Glycosuria , ® Polyurea ,Hyperosmolalaemia (plasma)  Hypovolaemia , (Water) ,Cellular dehydration ®­ Renal hypo function ,Ketoacidosis,Glycosurea ® polyurea.Hyper osmolalaemia , Cellular dehydration , Polyurea ® increased thirst.  Hypovolaemia

How does diabetes mellitus occur?
The hormone like thyroid hormone, adrenal hormone, growth hormone and glucagone tend to increase the level of glucose, where as insulin act to lower the blood sugar level. It is basically the imbalance of this hormone, which causes increased blood sugar. Most commonly this is because of the decreased production of insulin. 
Whenever a normal person eats food, immediately after taking food his blood sugar level increases, stimulating the secretion of insulin from the pancreas, which in turn brings back the blood sugar to the normal level. This auto regulatory mechanism become defective in patient of diabetes mellitus. So the blood sugar level continues to remain high for a very long period.  
In health the action of insulin and insulin antagonist hormone are delicately balanced. Imbalance of this hormone profile result in carbohydrate intolerance. 

Prevalence in India:
Recent studies from several parts of India have shown that the prevalence is increasing. The present over all prevalence is 5to 8 % and 2 to 4 % respectively in urban and rural population groups. With increasing age the prevalence also progressively increases. In India NIDDM constitute over 95 % of the total; the global picture is also similar. Male predominate in India where as the reverse is true in Western countries. 

Mechanism of pathogenesis of diabetes mellitus: 
1. Absolute deficiency of insulin production from the beta cells of islets of Langer hans -- often due to destruction of islets. 
   Causes for destruction of islets cells are:
a) Pancreatic disorder—inflammation, neoplasm etc.
b) Destruction of b cells from infection – viral infections like mumps, rubella, cox sacki virus etc.
c) Chemical agents –like alloxan, cyanide producing foods etc 
2. Abnormalities in insulin molecule. May be due to defects in the formation of insulin (synthesis    of an abnormal, biologically less active insulin molecule) 
3. Resistance of the target organs against the action of insulin (decrease insulin sensitivity due to decrease numbers insulin receptors) 
4. Excess production or relative excess of the hormone such as glucocorticods, glucagons and others, which counter act the effect of insulin.
5. Genetic defects – Mutation of insulin gene 
6. Auto immunity  
7. Heredity –usually seen among the relatives of diabetics. When both parents are diabetic the chance of developing it are 100%.                            
Environment risk factors: 
1. Sedentary life style (NIDDM) 
2. Malnutrition in early infancy and childhood may result in partial failure of function of b cells. 
3. Excessive intake of alcohol increase the risk of damaging pancreas and liver and by promoting obesity.  
4. Viral agent  -- b cell destruction -- mumps, rubella etc.
5. Chemical agents toxic to b cells. Eg: - Alloxan and cyanide producing foods.  
6. Stress--- following surgery, trauma etc.  
7. Obesity and overeating.

Blood sugar regulation by liver and muscles: 
Liver- when blood sugar tends to rise, liver stores it as glycogen and thus rise of blood sugar is checked. Similarly when blood sugar tends to fall liver mobilizes its glycogen store and speed up the rate of gluconeogenesis and thus restore the level to normal.  
Muscles - regulate the blood sugar level as normal by the same two ways as liver. 

Pathological changes:  
Pancreas: - b cells of the islets of langerhans show reduction in number. In early phase of NIDDM, b cells are normal in number or only slightly reduced. Resistance to insulin develops in target cells due to receptor insensitivity. Later, b cells also lose their sensitivity to hyperglycemic stimulus for releasing insulin. As a result insulin secretion loses its smooth and fine relationship with glucose level in the blood. In the early stages- the insensitivity of the receptors are compensated by over production of insulin and the accompanying hyperinsulinemia. Diabetes mellitus results when b cells start failing insulin production comes down. 

Vascular changes: - Thickening of the basement membrane leads to vascular occlusion. In microangiopathy there is specific involvement of small blood vessels. Microangiopathy affects several organ systems. The main pathological changes are seen in the retina (diabetic retinopathy), kidney (diabetic nephropathy), peripheral nerves (diabetic neuropathy) and heart (diabetic cardiomyopathy). These lesion leads to increased risk of ischemic heart disease, cerebrovascular accidents and ischemia to the limbs, resulting in intermittent claudication and peripheral gangrene. 

Retinopathy: - A specific change occurs in the vessels leading to loss of mural cells and the formation of microaneurysms. The occurrence of retinopathy is related to the duration and not to the severity of the disease. Once initiated the fundus changes are usually progressive. The early changes are venous dilation and appearance of small dot like microaneurysm in the perimacular area. Arterial blood is shunted and this leads to ischemia of the retina. Exudations are formed due to increased vascular permeability. Later hemorrhages are produced along with exudates. Large subhyaloid hemorrhage and vitreous hemorrhage may develop and vision is seriously impaired (may be due to rapture of newly formed blood vessels). When these hemorrhages are absorbed, organization by fibrous tissue occurs and multiple bands of retinitis proliferance develop. These leads to permanent visual impairment. The fibrous band may contract giving rise to retinal detachment. Sometimes in diabetic ketoacidosis with severe hyperlipidemia the fat gives a milky white appearance to the retinal arteries called “lipemia retinalis”
 
Renal lesions: -
Commonly seen in subjects who have had diabetes for over 20 years. 
Vascular changes: Arterisclerosis of retinal artery
Sclerosis of the arterioles and
Glomerulosclerosis. 
There is thickening of the glomerular capillary basement membrane. The establishment of the glomerulosclerosis is indicated by the presence of proteinuria. Further damage to the glomeruli results in the development of chronic renal failure.

Three stages of diabetic nephropathy- 
Stage 1. Asymptomatic microproteinuria (upto 100mcg/ minute of albumin may be lost in the urine. Normal subjects do not lose more than 19 mcg/ mt) in this stage the kidneys are enlarged, more vascular and the glomerular filtration rate is increased. 
Stage 2. Proteinuria more pronounced and easily detectable. Loss of 3.5 gm or more of protein in 24 hour may lead to the development of nephritic syndrome. Hypertension develops during this stage. 
Stage 3. Renal failure with azotemia, severe hypertension, and complication such as cardiac failure.
  The diabetic predisposed to develop urinary infection and therefore, acute and chronic pyelonephritis is very common. Fulminant urinary infection leads to ischemic necrosis of the renal papillae. This present as acute anuric renal failure. Fleshy masses may be passed in urine. These represent the necrosed papillae – papillitis necroticans.

Classification: 
A) IDDM
B) NIDDM
C) Malnutrition related diabetes mellitus
D)  Other types – Secondary to pancreatic, hormonal, drug induced, genetic and other abnormalities. 
2. Impaired glucose tolerance
A) Non obese
B) Obese
C) Associated with certain conditions and syndromes. 
3. Gestational diabetes mellitus
 
IDDM: - Insulin dependent diabetes mellitus. 
IDDM is called so, since provision of exogenous insulin is absolutely necessary for controlling the diabetes and restoring the metabolism to near normal. In IDDM there is progressive loss of b cells and in severe form they may be totally absent. Insulin secretion progressively decreases to almost nil when the disease is fully established. It is the most severe form and is lethal unless properly diagnosed and treated. 
NIDDM: - (non insulin dependent diabetes mellitus)
In NIDDM normal blood sugar level can be achieved even without providing exogenous insulin. Much more common than IDDM. Compatible with long survival if given adequate treatment.
Impaired glucose tolerance- describe a state intermediate or at risk group between diabetes mellitus and normality.
  
Clinical features:
Clinical features almost similar in both IDDM and NIDDM except the following. 
IDDM – NIDDM-
Abrupt onset Insidious onset.
Below the age of 30.       Over the age of 30.
Thin emaciated Obese.
Would develop ketoacidosis usually asymptomatic. (Unless promptly treated with insulin) 
 
Classical symptoms of diabetes mellitus:  
Polyurea: both quantity and frequency of urine increased. One of the early symptoms is disturbing polyurea at night, which wakes up the patient several times. 
Polydipsia: excessive drinking of fluids as a result of insatiable thirst. Several liters of fluid may be consumed to compensate for the polyurea. Even with excessive intake, patient may show sign of dehydration such as dryness of lips, mouth etc.  
Polyphagia: excessive consumption of food as a result of insatiable hunger.
Excessive intake ® worsen metabolic abnormality ® worsen the symptoms ® fatigue ® loss of weight.
(Excessive hunger with weight loss DM and hyperthyroidism) 
Autophagia (weight loss):  Loss of well being, muscular pain, fatigue, arthralgia, non-articular rheumatism, impotence and weight loss are other important features of diabetes mellitus. 

Other clinical presentations, which required full investigation to rule out diabetes mellitus, are:
1. Non-healing ulcers.
2. Recurrent respiratory tract or urinary tract infection.
3. Rapid changes in refraction of the eyes and premature cataract.
4. Steady and unexplained rapid weight loss.
5. Increased tendency for fungal infection
6. Unexplained peripheral neuropathy
7.  Premature onset of ischemic heart diseases, stroke or vascular occlusions,
8.  History of overweight babies and recurrent fetal loss.
9. Retinopathy
10. Impotence in male
11. Vague ill health. 

Diagnosis: 
1. In well-developed case with classical symptoms can be diagnosed clinically.
2. Blood sugar estimations are diagnostic. Any fasting blood sugar level of 120 mg /dl or more should be considered as abnormal. Postprandial blood sugar level above 180-mg/ dl also considered as abnormal. There will be many patients where fasting blood sugar will be normal but they show raised glucose level after taking meals. So ideally in all persons suspected to be suffering from diabetes mellitus a blood sample should be tested 2 hours after meals (post prandeal). In normal person the blood sugar level turn back to normal after 2 hour. But in Diabetics it remains high or keeps on rising. 
3.  Urine- Benedict’s test. Take 5 c.c. or one large teaspoonful of Benedict’s solution in a clean test tube and heat it well (no colour change on heating). Then add 8 drops of urine and boil for 2 minutes vigorously. Let it stands for 10 minutes. If sugar is present, clean blue colour changes to green, yellow, orange or brick red precipitate.
Blue colour --- no sugar
Green colour ---  +, 0. 5 % or less sugar
Yellow colour --- ++, 1 % sugar
Orange color --- +++. 1.5 % sugar
Brick red color --- ++++, more than2 % sugar.
4.Oral glucose tolerance test. Diagnosis in borderline cases is very difficult and is done by the test glucose tolerance test in which the blood samples are taken at half hourly interval after giving 100 gms of glucose orally and afterwards a graph is plotted according to the reading recorded.
 Glucose tolerance test -  
Subjects for glucose tolerance test are required not to take carbohydrate more than 300 gm a day at least for three days and to report on fourth day morning without having break fast. Venous blood is drawn for analysis. 100 gm of glucose dissolved in 300 ml of water is given orally just before drawing blood.
Blood sample for analysis are drawn at half an, one, two and three hour interval after taking sugar. 
In the normal subject: The maximum rise of blood sugar takes place between half and one hour but never beyond renal thrush hold (180 mg/ 100 ml). In one and half hour sample the sugar level may go below the fasting value due to stimulation of insulin secretion. But the level goes back to normal by the end of second hour. No glycosuria. 

In mild diabetes mellitus: Fasting level is normal. Between half and one hour the blood sugar level shoot sharply above the renal thrush hold causing glycosuria. But the level comes back to normal by two hours. It is due to delayed insulin mobilization which now requires a stronger stimulus than normal. 
In severe diabetes mellitus: Fasting blood sugar level is high. After administration of glucose it become higher and takes several hours to come down to the fasting level.

Prognosis:
 Once established, the diabetic state tends to be life long. Death may due to the following causes –
Renal failure, myocardial infarction, cerebro- vascular accident, diabetic coma and infections.
 
Management:
Dietary management- first step is to regulate the diet. An average amount of 200 to 250 gm of carbohydrate is agreeable to most of the patient.
A minimum 100 gm of carbohydrate is required to prevent ketosis and protein catabolism. The aim of treatment is to achieve normal blood sugar level throughout the day, to alleviate symptoms and to prevent complication.

Four pillars of diabetic management are
1. Diet.
2. Exercise
3. Drugs and
4. Patient education. 
 Protein intake should be 0. 8-gm/ kg body weight.

Diabetic Diet:   Approximately: -1800 Calories.
240 gm carbohydrate
60 gm protein
60 gm fats
 Morning: - Tea one cup with 20 ml milk or limejuice. 
 Break fast: - Milk one cup (170 ml). Bread one slice (25 gm). Egg one or one cup extra milk for vegetarian. 
 Mid morning: - Any one of the sugar free fruit. 
Lunch: - Atta or rice; three small chapattis or cooked rice (75 gm). Dal 100 gm. Green vegetables as much as desired. Oil for cooking – three tea spoon (15 ml) 
Evening tea: - Tea or coffee one cup with 20 ml milk. Bread one slice or 4 salt biscuits. 
Dinner: - Atta or rice; three small chapattis or cooked rice (75 gm). Meat or fish or chicken 25 gm. Curd 100gm. Green vegetables as much as desired. Oil for cooking – three tea spoon (15 ml). Any one of the sugar free fruit. 
Free food (can be taken as much as desired): - green leafy vegetables, tomatoes, cucumber, raddish, lime, clear soups, black coffee or tea without milk, butter milk, pickles, sour chutneys, pepper, etc 
Foods prohibited: - Glucose, sugar, honey and all sweets, jaggary, ice cream, pastries, cake, jam, jelly, squash, canned fruit juice, sugar cane juice, chocolates, bourvita etc. All aerated waters except soda water. 
Foods to be avoided: - Potatoes, mangoes, grapes, bananas, all dry fruits and nuts (e.g.: - pea nuts, almonds, cashew nuts etc) and all alcoholic drinks. 
[Diet chart taken from department of diabetics, Safdarjung Hospital, New Delhi]
Exercise: -
Regular exercise helps to reduce weight and improve sensitivity of tissues to the effect of insulin. It increases fitness, well-being and working capacity and improves cardio vascular function. It is essential component of the therapy of all forms of diabetes, particularly NIDDM. 

The bio chemical improvement include: 
1. Fall in blood glucose
2. Fall in triglyceride levels
3. Fall in serum cholesterol with increase in HDL cholesterol 
Walking 4 –5 km in one hour, swimming for 30 minutes, aerobic exercise for 30 –45 minutes, cycling or non-competitive games are all suitable exercise programs. The patient should be motivated to continue the exercise program regularly everyday. Overenthusiastic increase in exercise at irregular intervals may lead to hypoglycemia and cardiovascular complications such as ischemic episodes or cardiac failure.  
Yoga exercise: The yogic treatment restores the normal functioning of the pancreas and other glands of endocrinal system. The diabetic patients are advised to practice the yoga under expert guidance initially. 

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