Insulin with thiazide diuretics

A series of trials in elderly hypertensive subjects has shown a very pronounced reduction in cardiac events as a result of treatment based on thiazide diuretics. In the European Working Party on Hypertension in the Elderly (EWPHE) trial (13), total cardiovascular deaths were reduced by 38%, all cardiac deaths by 43%, and deaths due to myocardial infarction by 60%. Benefits in the Systolic Hypertension in the Elderly Program (SHEP) included a reduction in fatal and non-fatal myocardial infarction of 25% and major cardiovascular events of 32% (14) and were seen in those with and without electrocardiographic abnormalities at entry. The risk of heart failure was also reduced in patients taking chlortalidone-based therapy (15). Relative risk was similar in patients with and without non-insulin dependent diabetes meUitus absolute risk reduction was twice as great in the diabetic subjects (16). The Swedish Trial of Old Patients with Hypertension (STOP-Hypertension) reported a significant reduction in myocardial infarction and all-cause mortahty (17). In the MRC Trial in elderly adults (18), diuretic treatment reduced coronary events by 44% and fatal cardiovascular events by 35%. 

The effects of thiazide-type diuretics on carbohydrate tolerance cannot be ignored (50). There is a definite relation between diuretic treatment, impaired glucose tolerance, and biochemical diabetes, and a possible relation with insulin resistance (64). It is well estabhshed that the effect of thiazides on blood glucose is dose-related, probably linearly, while the antihjrpertensive effect has httle relation to dose (65-67). There is relatively httle information on the time-course numerous short-term studies have shown that the blood glucose concentration increases in 4-8 weeks (68). The evidence that current low dosages impair glucose tolerance in the long term is not entirely consistent, perhaps because of differences between studies... 

Effective antihypertensive therapy should include agents that do not adversely affect carbohydrate metabolic abnormalities. Commonly used antihypertensive agents, such as thiazide, thiazide-like diuretics and /3-blockers, are associated with glucose intolerance and increased insulin resistance (Sowers, 1991). In contrast, calcium antagonists and peripheral a-blockers (such as prazosin and terazosin) do not adversely affect glucose tolerance or insulin sensitivity. 

Answer D. Drugs that decrease extracellular potassium such as the thiazide and loop diuretics and adrenal glucocorticoids will lead to an increased requirement for insulin by making it more difficult to release the hormone from the B cells of the pancreas. Spironolactone is K sparing, tends to cause hyperkalemia, and does not interfere with the release of insulin. Stress conditions such as examinations also increase insulin requirement. 

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