Hypertension in Diabetes

Hypertension is a common accompaniment of type 2 diabetes and sets in the course of type 1 diabetes. Hypertension magnifies many fold the damage to the target organs (kidneys, heart, eyes etc) in diabetics and hence needs significant attention. Drug treatment in addition to lifestyle intervention is recommended to reach the prescribed goals by ADA and AHA (BP< 130/85 mm of Hg). Various drug trials on hypertensive diabetics are Appropriate Blood Pressure Control in Diabetes (ABCD), Fosinopril vs. Amlodipine Cardiovascular Events Randomized Trial (FACET), Irbesartan Diabetic Nephropathy Trial (IDNT). In perspective because of their efficacy, lesser side effects and good metabolic profile, ACE inhibitors rank as first-line treatment in both type 1 and type 2 diabetes.

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Management approach to a patient wıth dıabetes mellitus

TYPE 1 Diabetes Mellitus

All patients with type 1 DM should be exclusively on insulin therapy. The preferred form of therapy is basal bolus therapy which involves one (or more) injections of intermediate acting insulin and premeal bolus of regular insulin. Recently intermediate acting insulin has often been replaced with a long acting analogue (glargine or detemir) and the regular insulin with a short acting analogue (lispro or aspart). There are no fixed formulae for dose calculation and regular self home monitoring of blood glucose is used guide dose changes. Monitoring should be performed before and 2 hours after all major meals and also at 3.00 AM. The frequency of testing depends on the stability of control and consistency of lifestyle. Younger children, adolescents and professionals with unpredictable meal schedule must monitor more frequently to guide therapy and attain optimal   control. Adults with a consistent dietary regimen and daily schedule may monitor less frequently. Dose changes must never be made in response to a single abnormal blood glucose value. Ideally a trend of 3 or more abnormal values at the same monitoring point necessitates a dose change. The fasting blood glucose value dictates the dose of the night time long/intermediate acting insulin while each premeal blood glucose value reflects effect of the previous injection dose of the short acting analogue / regular insulin. The doses should be titrated to attain premeal blood glucose value of 70-120 mg/dl and a 2 hour post meal value of < 140 mg/dl.


TYPE 2

Pharmacotherapy should be initiated in patients with type 2 DM once a medical nutrition therapy and exercise has been unable to reach the goals. Metformin is the drug of choice in obese patients with type 2 diabetes while sulfonylureas are the preferred agents for lean patients with type 2 DM. Metformin is administered usually after the meal to minimize the gastrointestinal side effects. Dose escalation of metformin should be done at 4 weekly intervals with a maximum daily dose of 2-2.5 grams per day. Sustained release preparations of metformin are now available enabling single daily dosing. Glibenclamide, gliclazide and glipizide are administered twice a day, prior to breakfast and dinner while glimepiride can be given as a single daily dose. The escalation of the dose of sulfonylurea should not be done at intervals earlier than 7-14 days and this may be increased further in the case of glimepiride. In case the level of glycemia attained by a half maximal dose of sulfonylurea is unacceptable, it is preferable to add metfomin, or a thiazolidinedione rather than increasing the dose of sulfonylurea.

Thiazolidinediones are preferred as add-on therapy when sulfonylureas alone are not achieving acceptable glycemic control and metformin is either contraindicated or not tolerated.  Further, when a combination of maximal dose of sulfonyurea and metformin do not lead to euglycemia, thiazolidinediones can be added as a third agent.  A combination of the two insulin sensitizers is also a probable therpeutic option in obese patients with type 2 diabetes.

The newer secretogogues being quicker in onset and short acting need to be dosed t 5-10 minutes before major meals. They provide a better postprandial control and can be used accordingly in people with postprandial hyperglycemia and those with erratic meal schedule. During the course of type 2 DM the response to therapy goes off temporally and gradually necessitating increasing the number of oral agents and their doses. Finally most of type 2 DM cases may only be controlled adequately by using insulin therapy either alone or in recommended combinations with oral hypoglycemic agents.

Management of Lipid disorders

Most common cause of mortality and morbidity in diabetes (both type 1 and 2) is atherosclerotic cardiovascular disease owing to several risk factors, hyperlipidemia being the most prominent. Diabetic dyslipidemia is characterized by mild hypertriglyceridemia, low HDL and elevated LDL, the latter being in small, dense and oxidized (atherogenic) form. Both ADA and American Heart Association (AHA) recommend LDL cholesterol lowering as first priority followed by raising HDL and lowering triglycerides as 2nd and 3rd priority respectively. Both agencies recommend LDL goal and TG goals of 100 mg/dl and 200 mg/ dl respectively. HDL goal, however are different (ADA > 45 mg/dl and AHA 35 mg/dl). Five lipid lowering trials have examined and demonstrated a positive benefit of statins on CHD in diabetics. These trials are: The Scandinavian  Simvastatin Survival Study (4S), Cholesterol and Recurrent Events (CARE),Long Term Intervention with Pravastatin in Ischemic Disease (LIPID), Air Force/Texas Coronary Atherosclerosis Programme(AF-CAPS) and Veterans Affairs High Density Lipoprotein Cholesterol Intervention Trial ( VA-HIT)  and  used statins and fibric acid derivatives. Drug therapy for HDL and triglyceride are taken up only after behavioral modification (i.e. weight loss, increased physical activity, and smoking cessation) has been tried.

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Diabetes mellitus presentation

Type 1 diabetes

The severity of the insulin deficiency and the acute­ness with which the catabolic state develops deter­mine the intensity of the metabolic derangements. An ab­solute deficiency of insulin results in excessive accu­mulation of circulating glucose and fatty acids, with consequent hyperosmolality and hyperketonemia. Weight loss despite normal or increased appetite is a common feature of type 1 diabetes when it develops subacutely over a period of weeks. The weight loss is initially due to depletion of water, glycogen, and triglyceride stores. Chronic weight loss due to re­duced muscle mass occurs as amino acids are di­verted to form glucose and ketone bodies. Increased urination is a conse­quence of osmotic diuresis secondary to sustained hyperglycemia. Thirst is a conse­quence of the hyperosmolar state, as is blurred vision, which often develops as the lens and retina are ex­posed to hyperosmolar fluids. Lowered plasma volume produces dizziness and weakness due to postural hypotension when sitting or standing. Total body potassium loss and the general catabolism of muscle protein contribute to the weak­ness. Ketoacidosis occurs when insulin deficiency is severe and of acute onset.  It exacerbates the dehydration and hyperosmolality by producing anorexia, nausea, and vomiting, thus interfering with oral fluid replace­ment. As plasma osmolality exceeds 330 mosm/kg, impaired consciousness ensues. With progression of acidosis to a pH of 7.1 or less, deep breathing with a rapid ventilatory rate (Kussmaul respiration) occurs and progresses to se­vere circulatory collapse with pH 7.0 or less.

Type 2 diabetes

Many patients with type 2 diabetes have an insidious onset of hyperglycemia and may be relatively asymptomatic initially. This is particularly true in obese patients, whose diabetes may be detected only after glycosuria or hyper­glycemia is noted during routine laboratory studies. The classic symptoms of polyuria, thirst, recurrent blurred vision, paresthesias, and fatigue are manifestations of hyperglycemia and osmotic diuresis and are therefore present late in the course of disease. Chronic skin infections are common. Generalized pruritus and symptoms of vaginitis are frequently the initial complaints of women with type 2 diabetes. Di­abetes should be suspected in women with chronic candidal vulvovaginitis as well as in those who have delivered large infants (4.1 kg) or have had polyhydramnios, pre-eclampsia, or unexplained fetal losses. Occasionally, a man with previously undiag­nosed diabetes may present with impotence.

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