Diabetes Mellitus, its classification and clinical features.

Diabetes Mellitus is clinical condition characterised by hyperglycaemia(high blood sugar), due to deficiency or decreased effect of insulin. Hyperglycaemia produces the classical symptoms of polyurea, polydipsia and polyphasia. The disease is chronic and affects the metabolism of carbohydrate, protein, fat, water, and electrolytes sometimes with severe result.

Diabetes Mellitus or Diabetes

Diabetes mellitus is a clinical syndrome characterised by hyperglycaemia (high blood sugar), due to deficiency or decreased effect of insulin. The hypergly- caemia produces the classical symptoms of polyurea (frequent urination), polydipsia (increased thirst), and polyphagia (increased hunger). The disease is chronic & affects the metabolism of carbohydrate, protein, fat, water and electrolytes sometimes with severe results.
The metabolic activity is disturbed resulting permanent and irreversible functional & structural changes in the cells of the body (particularly of vascular system, so called the complications of the diabetes most commonly affect the eye, the kidney and the nervous system.

Incidence of Diabetes :

Diabetes mellitus is the most common Endocrine disorder. The prevalence of disease in India is over two percent of population, although about half of those are unaware of the fact (disease) and may remain undetected.

Classification of Diabetes Mellitus :

They are classified as follows:
1. The Juvenile-onset or Insulin-dependent diabetes mellitus: Usually develop within 1st 40 years of life in patients with normal or sub normal weight. In majority of cases patient develop severe symptoms of diabetes acutely within weeks or months and if not treated with insulin they will rapidly develop fatal Ketoacidosis. Since administration of insulin is essential for their survival. it is also called as insulin dependent diabetes mellitus.
2. The Maturity onset or Insulin resistance diabetes mellitus: Usually occurs in middle- aged or elderly patients, often obese & their hyperglycaemia can usually be controlled by diet alone or with an oral hypoglycaemic drug. This refers to non insulin dependent diabetes mellitus. Insulin is detectable in the plasma of almost all patients in this category, and so they are less prone to develop ketosis. Maturity onset or adult diabetes is less severe than juvenile-onset type. Complications associated with long-term diabetes occur in both types. Many patients with maturity –onset diabetes have a long history of mild symptoms which may come & go, and ignored or misdiagnosed for years before correct diagnosis is made.
3. Gestational diabetes : This type occurs in pregnant female, who never had diabetes before. They have a high blood sugar level during pregnancy. It may develop type 2 (Insulin Resistance) diabetes mellitus in future.
4. Other types of diabetes is as follows:
• Congenital diabetes due to genetic defect of insulin secretion
• Cystic fibrosis related diabetes
• Steroid induced diabetes by high doses of glucocorticoids and
• Several forms of monogenic diabetes.
All forms of diabetes can be treated by insulin injection except insulin resistance (type 2) diabetes which is controlled by anti-diabetic drugs. Both type1 and type2 diabetes are chronic conditions and require life long treatment.
• Pancreas transplants-tried with limited success in type 1.
• Gastric bypass surgery-successful in morbid obesity & type 2 DM.
• Gestational diabetes usually subsides after delivery.

Clinical Features of Diabetes Mellitus :

Symptoms :
Diabetes may be presented in one of the following ways:
• Patients are noted to have glycosuria in some routine checkups, for employment purposes, for insurance, or pre-operatively with few or no symptoms and no abnormal physical signs.
• Some patients come with few or all classical symptoms of diabetes including thirst, polyurea, polydipsia, nocturia, , tiredness, loss of weight, white marks on clothing, pruritis vulvae or balanitis, a change in refraction mostly in the direction of myopia, par aesthesia or pain in the limbs and impotence.
• Diabetes may appear as a fulminating ketoacidosis with an acute infection or without evidence of precipitating cause. In such cases epigastric pain and vomiting may be the presenting complaints. This occur mostly in juvenile- onset type with acute medical emergency.
• Patient may come with symptoms due to one of the complications of diabetes like failing vision; anaesthesia in the limbs or pain in legs due to diabetic neuropathy, peripheral vascular disease or to a combination of two; impotence; infection of skin, lungs, or urinary tract.
It is important to know that the severity of the classical symptoms of clinical diabetes , particularly thirst, polyurea, nocturia, pruritis vulvae and white marks on clothing are related to the severity of glycosuria.
Physical signs:
• Cases of diabetes without complications often show no abnormal physical signs.
• In some cases vulvitis or balanitis may be present, because the external genitalia are more prone to fungal infection (monilia) which grows on the skin and mucous membranes contaminated by glucose.
• Dehydration, with a loose dry skin which lifts in folds, and a dry furred tongue with cracked lips is the most striking features of fulminating diabetes.
• Reduced intra-ocular pressure.
• A low rapid pulse with a low blood pressure.
• Breathing may be deep with foetid and sickly sweet smell of acetone.
• Mental apathy and confusion may be present or there may be stupor or even coma.
• Ophthalmoscopy may show typical appearance of diabetic retinopathy.
• The most constant early signs of diabetic neuropathy are depression or loss of ankle jerks & impaired vibration sense of the legs.
• Diabetic neuropathy may be indicated by proteinuria.
• Potential and latent diabetes may have no complaint with no abnormality seen on examination. Potential diabetes are predisposed to coronary arterial and peripheral vascular disease. They may show abnormal lipid response to oral contraceptives. They have a high incidence of still-born babies. They may become much overweight at a time with no detectable abnormality in terms of carbohydrate intolerance.

Complications of Diabetes Mellitus :

Diabetes mellitus leads to many complications if not treated properly well in time. Complications are of two types:
1. Acute complications
2. Chronic complications
1. Acute complications :
• Hypoglycaemia
• Diabetic ketoacidosis
• Diabetic coma
2. Chronic complications :
• Cardio vascular disease
• Retinal damage
• Chronic renal failure
Proper treatment with blood pressure control and regulated lifestyle, i.e. factors like smoking cessation, regular exercise/walking and maintaining a healthy body weight, minimise the risk of complications.

Chemical Pathology of Diabetes mellitus :

Insulin is the main hormone that regulate glucose uptake from the blood into human cells initially muscle & fat cells but not the central nervous system. So deficiency of insulin or the insensitive receptors of insulin plays an important role in regulating all types of diabetes mellitus.
Humans are capable of digesting carbohydrates as food; starch &sugar (disaccharides) are converted within few hours to glucose (monosaccharide) the main source of energy used by the human body. Insulin is released into the blood by beta cells found in Islet of Langerhans of the pancreas, after eating to utilise glucose. About 2/3rd of insulin is utilised by body cells to absorb glucose from the blood as fuel, for conversion to other needed molecules, or for storage.
Insulin also controls conversion of glucose into glycogen which is stored in the liver and muscle cells. Hypoglycaemia leads to reduced release of insulin from the beta cells of pancreas & reverse conversion of glycogen to glucose. This process is controlled by the hormone Glucagons which antagonise the action of insulin. Thus glucose forcibly released from the liver cells in the form of glycogen re-enters in the blood stream. This happens normally in the liver cells when the level of insulin is low. Increased insulin levels enhance the anabolic activity like cell growth, protein synthesis and fat storage. Lack of insulin is the main signal in converting metabolism from a catabolic to an anabolic process and vice versa. A low insulin level is signal for entering or leaving Ketosis (i.e. fat burning metabolic phase). When the quantity of insulin available is inadequate, if the cells respond poorly to insulin (insulin resistance) or if insulin itself is defective, then glucose will not be absorbed properly by body cells as required nor stored in the liver and muscles. It leads to persistent high level of blood glucose, poor protein synthesis & other metabolic disturbances like Acidosis. When glucose in the blood is raised beyond its renal threshold (about 10 mmol/L) such as in pregnancy, reabsorption of glucose in the proximal renal tubule is incomplete & part of the glucose remains in the urine (glycosuria). This increase the osmotic pressure of the urine and inhibits reabsorption of water by the kidney resulting increased urine production ( Polyurea) & increased fluid loss causing dehydration and increased thirst (Polydipsia).

Diagnosis of Diabetes Mellitus :

If patient is having symptoms but are not frank case of diabetes, evaluation of the patient starts with thorough history and physical examination.
Proper history- about symptoms
-risk factors
-about previous medical problems
-current medications
-family history of diabetes
-about high cholesterol or heart disease
-lifestyle & personal habits
To confirm the diagnosis of diabetes a number of tests are available which are:
Urine test for Glycosuria:
Urine test for glycosuria is done by a dip paper Stick impregnated with an enzyme preparation which turns purple when dipped in urine having glucose. This is a rapid and specific qualitative test for glucose.
Fasting Blood Sugar :
Patient is asked for complete fast for 8 hours before blood sample is taken (i.e. morning sample). If blood glucose level is more than or equal to 126 mg/dL without eating anything, is diagnosed as diabetes. If fasting blood glucose level is more than 100 but less than 126 mg/ dL is considered to be pre-diabetes. In this case patient is at high risk & develops diabetes in the near future.
Oral glucose Tolerance Test:
Patient fasts over night and blood sample is taken then 2nd sample is taken after 2 hrs. after drinking 50gm glucose dissolved in 200ml of water orally. Blood sample is estimated after 2 hours.
• If blood glucose level is 200 mg/dL or more, the patient has diabetes.
• If blood glucose is between 140 and 199 mg/dL then patient is with impaired glucose tolerance (IGT) i.e. in pre-diabetic condition.

Glycolated Haemoglobin or Haemoglobin A1c :
This test is done to measure how high blood glucose levels have been over about the last 120 days (This test is based on the average life span of RBC (i.e. 120 days).
• Excess blood glucose hangs over the Hb in RBC & stays there for life time.
• Percentage of Hb with excess blood sugar can be measured.
• A haemoglobin A1c test is best measurement for blood glucose control in known diabetic.
• If haemoglobin A1c test result is 7% or less indicates good glucose control.
• If it is 8% or more indicate blood sugar levels are too high for long time.
• More than 6.1% is highly suggestive of diabetes.
• Haemoglobin A1ctest is required every 3-6 months with known diabetic & more frequently in those having in achieving and maintaining good blood sugar control.

Checkups for Diabetes complications :

• Eye: At least once in a year to exclude diabetic retinopathy a major cause of blindness.
• Regular urine examination for protein (albumin) 1or2 times in a year to exclude diabetic nephropathy a major cause of kidney failure.
• Sensation in the legs checked regularly to exclude diabetic neuropathy which leads to diabetic ulcer & gangrene which often results to amputation of feet or legs.
• Physician or Health provider should examine the feet and lower legs at every visit for cuts, scrapes, blisters or other lesions which may get infected.
• Patient screened for high BP and high cholesterol which can cause heart disease.


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