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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