| ID | 60 |
|---|---|
| Name | DIABETES MELLITUS1 |
| Cause | |
| Signs Symptoms | |
| Diagnosis | Diagnosis of diabetes:2 Patient complains of symptoms suggesting diabetes- 1. Test urine for glucose and ketones. 2. Measure random &/or fasting blood sugar (two samples). Diagnosis confirmed fry-Fasting blood sugar (FBS)- > 7.0 mmol/1 (126mg/dl). Random blood sugar (RBS)- > 11.1 mmol/1 (200mg/dl). 3. Indications for oral glucose tolerance test (OGTT). a. Fasting blood sugar 6.1 -7.0 mmol/1 (110-126mg/dl). b. Random blood sugar 7.8-11.0 mmol/1 (140-198mg/dl). Preparation for oral glucose tolerance test (OGTT)- i. Unrestricted carbohydrate diet for 3 days. it. Fasting overnight for at least 8 hours. iii. Rest for 30 minutes (with no smoking). iv. Sampling- blood sugar in measured before and 2 hours after a 75gm oral glucose drink, v. Stay for the duration of the test, with no smoking or further drinking. Interpretation ofOGTT- Fasting 2 hrs after glucose drink Normal glucose 6.1-6.9 mmol/l < 7.8 mmol/l tolerance (110-125mg/dl (< 140mg/dl) Impaired glucose < 7.0 mmol/1 7.8-11.0 mmol/l tolerance (< 126mg/dl) (140-199mg/dl) Diabetes melitus > 7.0 mmol/1 > 11.1 mmol/l (> 126mg/dl) (> 200mg/dl) *The use fo HbAic for diagnosis is uncertain; it is mostly done to assess glycaemic control in a known diabetic patient. |
| Investigations | Investigations: 1. Urine testing- (urine should be taken 2 hours after meal) i. Glycosuria- a positive response indicates that the urinary glucose concentration exceeds 10-20mg./100ml. ii. Detection of ketone bodies in urine. 2. Random blood sugar- a random blood sugar exceeding 250mg/100ml (14 mmol/1) is amlost certain to diagnose diabetes. 3. Oral glucose tolerance test- a fasting glucose level above 120mg/100ml or a glucose level above 180mg/100ml 2 hours after glucose indicated diabetes. 4. Glycated haemoglobin (KbA1) measurements: In diabetes, hemoglobin becomes glycated by slow non-enzymatic ketoamine reactions between glucose and other sugars and the free amino groups on the a and P chains of hemoglobin. The major form of glycated haemoglobin (HbAt) is hemoglobina aic (HbAlc) where glucose is the carbohydrate. HbAlc comprises 4-6% of total glycated hemoglobin (HbA]). The hemoglobin aic fraction is abnormally elevated in diabetic persons with chronic hyperglycemia. The rate of formation of HbAlc is directly proportional to the ambient blood glucose concentration; a rise of 1 % in HbAlc corresponds to an approximate average increase of 2mmol/l (36mg/dl) in blood glucose. The assessment of glycated haemoglobin provides an accurate measure of glycaemic control over a period of weeks to months in a known diabetic patient. Normal glucose tolerance Impaired glucose tolerance Diabetes mellitus 2 hrs after glucose drink < 7.8 mmol/1 (< 140mg/dl) 7.8-11.0 mmol/1 (140-199mg/dl) > 11.1 mmol/1 (> 200mg/dl) |
| Management | Management: Most diabetics are best managed in diabetic clinics where there is close liaison between expert physicians, special experienced nursing stuff, ophthalmologist, dietician and chiropodist. Management includes: A. Treatment B. To educate the patient regarding the disease, treatment and complications. C. Followup and supervision. Methods of treatment: a. Diet alone- 50% can be controlled adequately b. Diet + Oral hypoglycaemic agent- 20-30% cured c. Diet and Insulin- 20-30% cured. Types of diet:2 1. Low-energy, weight-reducing diet (a daily deficit of 500 kcal)- this is indicated for the obese diabetic patients treated with insulin to minimise the weight gain which insulin can promote. This variety of diet induces a weekly weight loss of about 0.5kg. 2. Weight maintenance diet- this is indicated for the diabetics with normal body weight, where energy intake remains almost constant; usually high in carbohydrate and low in fat. Advice for daily energy requirment: 1. Obese, middle aged or elderly patient with mild diabetes needs 1600 kcal daily. 2. Elderly diabetic but non-obese needs 1800 kcal daily. 3. Young active diabetic patient needs 1800-3000 kcal daily. Specific dietary composition with calorie distribution:’2 A dietary recommendation for diabetic patients made by the ‘British national diet’2 is given below- i. Carbohydrate- 45-60% of total calorie ii. Protein- 10- 15% of total calorie. iii. Fat- 30-35% of total calorie. - saturated fatty acids < 10% - monounsaturated fatty acids 10-20% - polyunsaturated fatty acids < 10% iv. Fruit/Vegetables - 5 portions daily. American diabetes association (ADA)1 has given a current revised dietary recommendation. According to that recommendation, type 2 diabetic patients are advised to reduce their carbohydrate content considerably than previous (55-60%) diet. Obese type 2 patients are advised to limit their carbohydrate by substituting noncholesterologenic monounsaturated oils such as olive oil, canola oil, nuts oil. In type 1 diabetic patient on intensive insulin therapy, carbohydrate should be given by ‘carbohydrate counting1 i.e 1 unit of regular insulin should be administered for each 10 to 15gm of carbohydrate to be taken in a meal. Carbohydrate content should contain 20-35gm of dietary fiber. In fat content cholesterol should not be more than 300mg daily. * Sweets, sweet products and sweet fruits are restricted. Instead, artificial sweeteners such as, aspartame, saccharin, sorbitol are used now a day very popularly by the diabetic patients. * Citrus fruits and one banana can be taken in a day. * Amount of salt- 3-6gm daily. |
| Introduction | Introduction:1,2 Diabetes mellitus is a clinical syndrome characterised by hyperglycaemia due to absolute or relative deficiency of insulin, i.e due to either a deficiency of insulin secretion or, a combination of insulin resistance and inadequate insulin secretion to compensate. Diabetes is the most common endocrine disorder. It affects almost all the systems of the human body, since lack of insulin affects metabolism of carbohydrate, protein and fat and also causes a significant disturbance in water and electrolyte balance. TYPE 1 DIABETES MELLITUS1,2 Type 1 diabetes mellitus occurs due to pancreatic P-cell destruction predominantly by- i. an autoimmune process (> 90%), and less commonly by-ii. idiopathic or unknown causes (< 10%). The immune mechanism involved in type 1 diabetes is a slow T cell-mediated autoimmunity. About one-third of these are due to genetic linkage with special predisposition of human leucocyte antigen (HLA). The particular haplotypes associated with type 1 diabetes are HLA-DR3 and HLA-DR4. Some viral infections also known to cause autoimmune damage to P-cells. Type 1 diabetes occurs mainly in the juvenile age group, with highest incidence in between 10 to 14 years, especially in the nonobese and rarely occurs in the adult life. It is usually associated with ketoacidosis if not treated duly. In type 1 diabetes, circulating insulin is almost absent, plasma glucagon is elevated, but the pancreatic p-cells fail to respond to all insulinogenic stimuli. As a result, insulin supplementation is essentially required to reverse this catabolic state, reduce blood glucose, prevent ketoacidosis, and reduce the plasma glucagon. TYPE 2 DIABETES MELLITUS1 Type 2 diabetes is the most prevalent form of diabetes (> 90%), results from insulin resistance with a defect in compensatory insulin secretion. It represents a heterogeneous group comprising milder forms of diabetes that occur predominantly in adults (most are over 40 years) but occasionally in juveniles. In this insulin production by P-cells is sufficient to prevent ketoacidosis but not adequate to prevent hyperglycemia in the face of increased needs owing to tissue insensitivity. Although, in most cases of type 2 diabetes, the cause is unknown, several inter related factors are considered responsible for developing tissue resistance to insulin and impaired P-cell response to glucose such as aging, a sedentary lifetyle, and abdominal-visceral obesity. In addition, over eating specially when conbined with obesity and interactivity, contribute to aggravate the hyperglycemia. A strong genetic influence (with positive family history) has also been established in developing type 2 diabetes by different epidemiologic studies. Repeated pregnancy may also contribute to cause type 2 diabetes. |
| History | |
| Etiology | |
| Clinical Features | Clinical features: Presentation: 1. Many patients are first noted to have glycosuria in the course of some routine examinations. They may have had few or no symptoms and no abnormal physical signs. 2. Some patients present with the classical symptoms of diabetes e.g. thirst, polydipsia, polyuria, nocturia, tiredness, loss of weight, white marks on clothing, pruritus vulvae or balanitis, impotence, myopia, and paraesthesia in the limbs. 3. Diabetes may first present as a fulminating ketoacidosis associated with an acute infection and in such cases epigastric pain and vomiting may be the presenting complaints. 4. Patient may present with symptoms due to the complications of diabetes. Physical signs: Cases without complications will usually show no abnormal physical signs. In some cases vulvitis or balanitis may be found. In the fulminating case the most striking features are those of dehydration. The intra ocular pressure may be obviously reduced. A rapid pulse and a low blood pressure are found. Breathing may be deep and sighing in the acidotic patient, the breath is usually foetid and the sickly sweet smell of acetone may be noticeable. Apathy and confusion may be found or there may be stupor or even coma. Evidences of complications of diabetes may be noted e.g. diabetic retinopathy, diabetic neuropathy, loss of ankle jerks and impaired vibration sense in the legs. |
| Preventions | |
| Treatment | Treatment: Type 2 diabetes 1. Diet control roughly (1200-1500) kcal & weight reduction (see above). 2. Exercise- regular moderate exercise or as advised by the physician. 3. If dietary control and exercise fail then add- oral hypoglycaemic agents. a. Sulphonylureas: Usually given in non-obese patients, i. First-generation- e.g Acetohexamide, Chlorpropamide, Tolazamide & Tolbutamide- these are not currently prescribed in most cases. For dosage & other informations, see in the therapeutic section. ii. Second-generation- e.g Glibenclamide, Glipizide, Gliclazide, Glimepiride, Glyburide & Glyquidone- among these, glibenclamide has got severe hypoglycaemia effect & hence is avoided particulaly in the elderly; other preparations are with least side-effects & widely used now-a-day. Dosage: Glipizide21- initially 2.5-5mg daily, adjusted according to response; max. 40mg daily; upto 15mg may be given as a single dose before breakfast; higher doses divided. Gliclazide21- initially 40-80mg daily, adjusted according to response; up to 160mg as a single dose with breakfast; higher dose should be given in divided doses; max. 320mg may be given daily. Glimepiride1- Img once daily; maximal recommended dose is 8mg daily. It has a long duration of action with a pharmacodynamic half-life of 5 hours. Once-daily administration improves patient’s compliance. Glyburide1- usually starts with 2.5mg daily; average maintenance dose is 5-10mg daily given as a single morning dose; some authorities suggest that 10mg is the maximum daily dose. Glibenclamide21- initially 5mg daily as single dose at breakfast, increasing if necessary by 2.5-5mg at weekly intervals to max. 15 mg daily. b. Meglitinide analogs: Drugs currently available belonging to this group are Nateglinide and Repaglinide. These are insulinotropic agents (secretagogue) and used as ‘oral prandial glucose regulators’. These drugs can be used as monotherapy or in combination with metformin. Dosage: Repaglinide 1- the starting dose is 0.5mg three times daily 15 minutes before each meal; the dose can be increased to a maximal daily dose of 16mg. Hypoglycemia is the main side effect. Nateglinide 1- the usual recommended starting and maintenance dose is 120mg three times daily before meals. Its main side effects are hypoglycemia and weight gain. c. Biguanide: Metformin is the only available drug of this group. It can be given alone or incombination with sulphonylureas (synergistic); usually indicated in the obese patients, but may also be given in non-obese one. Dosage: Metformin21- initially 500mg twice daily or 850mg daily with meals, increasing gradually if necessary to max. 3gm daily. Reduce to maintenance dose, usually 500mg thrice or 850mg twice daily. d. Thiazolidinediones: These are newer antihyperglycemic agents, act by sensitizing peripheral tissue receptors to insulin, i.e ameliorates insulin resistance in the peripheral tissues. Currently available drugs are Pioglitazone, Rosiglitazone, Troglitazone. But, at present pioglitazone is only approved for use in combination with insulin, because, the other two have serious adverse effects such as, troglitazone may cause liver failure and rosiglitazone may cause congestive heart failure when given with insulin. Dosages:1'21 Pioglitazone when given alone, initially 15mg or 30mg once daily; may be increased later up to 45mg once daily, when given with insulin, matformin or sulfonylurea, dose is as same as pioglitazone alone. It may be taken with or without food by a full glass of water. e. Alpha-glucosidase inhibitors: Acarbose and Miglitol. These are oral hypoglycemic agents; they act competitively by inhibiting intestinal a-glucosidase enzymes, as a result reduction in carbohydrate digestion and absorption. The main adverse effect is flatulence (in 20-30% of patients), which is caused by undigested carbohydrate reaching the lower bowel, where gases are produced by bacterial flora. Dosage: Acarbosel- the recommended starting dose is 25mg once or twice daily. This can be increased slowly over 1 or 2 months to a maximum of 100mg three times daily. 4. Insulin therpay in type 2 diabetes: i. Type 2 diabetes, whenever good control with diet and oral hypoglycemic agent is no longer attainable (i.e secondary failure with sulphonylurea therapy). ii. In malnutrition related diabetes mellitus (MRDM). iii. Type 2 diabetes, whenever special metabolic stresses arise in consequence of operations, febrile illness or accidents (the need of insulin therapy is temporary) iv. During diabetic emergencies such as ketoacidosis, serious breakdown of control, v. Pregnant diabetic women when diet alone fails to maintain therapeutic goal. Side-effects of insulin therapy: a. Hypoglycaemia b. Weight gain c. Peripheral oedema (insulin treatment causes salt and water retention in the short term) d. Insulin antibodies (animal insulins) e. Local allergy (rare) f. Lipodystrophy at injection sites. 5. Special care of the diabetes patients i. Care for personal hygiene specially care of the teeth, toenails, skin & teeth. ii. Care for infection, iii. Avoid injury. Type 1 diabetes 1. Diet- diabetic (see above). 2. Exercise- regular moderate exercise or as advised by the physician. 3. Insulin therapy (at starting): i. Conventional insulin therapy: The regimen of insulin therapy usually depends on the glycaemic status of the patients & desired degree of its control. In majority cases 2 (or more) injections are required for achieving expected result. Once-daily dose usually not enough for satisfactory glycaemic control, except in cases of elderly patients. In cases of 2-daily injections, usually a short-acting (soluble) & an intermediate-acting insulin (isophane insulin) are given in combination before breakfast and the evening foods. Now-a-days, various pre-mixed formulations of soluble & isophane insulins are available. Adjusting insulin dosages in conventional insulin therapy, given as below- Blood glucose (mg/dl) Regular insulin (units) Breakfast supper 51-100 8 4 101-150 10 5 151-200 12 6 201-250 14 7 251-300 16 8 >300 20 10 ii. Human insulin may be given when * High insulin requirements. * Gestational diabetes. * Local sensitivity reaction at the site of injection, iii. In case of pancreatectomy- 20-30 units are usually needed per day. 4. Use of oral diabetic agent in type 1 diabetes: i. Metformin can be given as adjuvant therapy in type 1 particularly in the obese. To educate the patient: 1. Regarding disease- i.e - therapy should be continud life long, - role of food, etc. 2. Regarding insulin therapy- - injection technique - urine testing - home blood glucose monitoring. 3. Care of foot, physical excercise. 4. Regarding hypoglycaemic coma and management (i.e always carry some glucose) etc. Follow-up & supervision: 1. Regular follow-up visit (weekly or monthly)- Body wt, BP, blood & urine test, visual acuity and signs of neuropathy should be examined. 2. Annual follow-up visit-Detailed eye examination, renal function tests, assessment of cardiac functions etc. should be done. Complications of diabetes: A. Acute- 1. Hypoglycemia 2. Diabetic ketoacidosis 3. Non-ketotic hyperosmolar diabetic coma. 4. Lactic acidosis. B. Longterm- 5. Diabetic retinopathy. 6. Diabetic neuropathy. 7. Diabetic nephropathy. 8. Heart disease. |
| Complications | |
| Prognosis | |
| Types | |
| Classification | Classification of diabetes mellitus:1-2 A. Type 1 (Insulin-Dependent Diabetes Mellitus- IDDM) 1. Immune-mediated 2. Idiopathic B. Type 2 (Non-Insulin-Dependent Diabetes Mellitus- NIDDM) 1. Nonobese type 2 (NIDDM) 2. Obese type 2 (NIDDM) C. Other specific types of diabetes 1. Genetic defects of pancreatic P-cell function. a. Maturity-onset diabetes of the young (MODY 1-6): A rare subgroup, belongs to type 2 diabetes (NIDDM). b. Diabetes mellitus associated with a mutation of mitochondrial DNA 2. Genetic defects of insulin action, a. Type A insulin resistance b. Leprechaunism c. Rabson-Mendenhall syndrome d. Lipoatrophic diabetes 3. Diabetes due to pancreatic diseases (exocrine part). 4. Endocrinopathies (i.e excess endogenous production of hormonal antagonists to insulin). 5. Drug or chemical induced diabetes. 6. Diabetes due to viral infections (e.g congenital rubella, mumps, Coxsackie virus B) 7. Uncommon forms of immune-mediated diabetes. 8. Diabetes associated with genetic syndromes (e.g Down’s syndrome, Klinefelter’s syndrome, Turner’s syndrome, Wolfram’s syndrome; diabetes insipidus, diabetes mellitus, optic atrophy, nerve deafness, Friedreich’s ataxia, myotonic dystophy). D. Gestational diabetes. |
| Observation | |
| Pathology |
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