Summary. Insulin secretory responses to paired intravenous and oral glucose loads were determined in 38 nonobese individuals classified as normal (nondiabetic) subjects, "mild" diabetics (fasting blood glucose below 105 mg per 100 ml), or "moderate" diabetics (fasting glucose below 192 mg per 100 ml). Studies were also performed in 29 obese persons who were similarly grouped. The intravenous load was given to assess the alacrity of hormonal release after glycemic stimulus, and the oral glucose to determine how the speed of initial insulinogenesis modifies the disposition of ingested carbohydrate.In the nonobese group, normal subjects responded to massive hyperglycemia after rapid injection of glucose with immediate and maximal outpouring of insulin, in contrast to a desultory insulinogenic response in patients with mild diabetes, and no initial response at all in moderate diabetics. During oral glucose tolerance tests, the much faster clearance of blood sugar in nondiabetic subjects was actually associated with lower absolute insulin output than was found in mildly diabetic patients, since the latter exhibited delayed hyperinsulinemia in concert with prolonged hyperglycemia. Moderate diabetics never showed excessive insulin release despite even greater hyperglycemia. An empirical "insulinogenic index," the ratio relating enhancement of circulating insulin to magnitude of corresponding glycemic stimulus, was used to compare the secretory capacities of respective groups. Despite the higher absolute hormonal output after oral glucose in mild diabetics, the index revealed that insulin release in normal subjects was proportionally more than twice as great. This relatively greater normal secretory response declared itself shortly after the administration of glucose by either route, and was maintained throughout both tests.In the 29 obese individuals, differences among groups were essentially the same as in persons of normal weight. Obese nondiabetics did show much larger absolute insulinogenic responses during both tests than did nonobese controls. Since corresponding glucose tolerance curves were also higher, the mean insulinogenic indexes for obese subjects were not statistically greater. Moreover, when comparable glucose curves of obese and nonobese controls * Submitted for publication September 13, 1965; ac- were matched, the apparent hyperinsulinemia associated with obesity was again reduced to insignificance. At the same time, a tendency toward perpetuation of higher insulin levels in overweight normal subjects and mild diabetics, in response to both glucose loads, suggested that obesity per se does induce a state of peripheral insulin resistance.The data indicate that normal beta cells respond instantly to a glycemic stimulus, whereas diabetic islets react sluggishly, and that proportionally greater insulinogenesis accounts for faster disposal of postprandial hyperglycemia in nondiabetics than in diabetics, in both nonobese and obese individuals. By tracing a rational sequence of events within the beta cell-fro...

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Both recognition and prevention of drug-induced hypoglycemia require awareness of the clinical conditions favoring its occurrence and the drugs and drug combinations most likely to cause it. Restricted food intake, age, hepatic disease and renal disease are the main predisposing factors, individually and even more so in combination. Everyone in general, and insulin-requiring diabetics in particular, should always eat carbohydrate whenever they drink alcohol. Sulfonylurea hypoglycemia has been reported often in diabetics older than fifty years, with more cases treated with chlorpropamide being reported than cases treated with other sulfonylureas ; it should therefore be used warily in older patients, and only when they are under daily observation by family or friends. In elderly diabetics taking any sulfonylurea agent, warfarin should be used for anticoagulation instead of bishydroxycoumarin, indomethacin for arthritic pain instead of phenylbutazone, and another agent than sulfisoxazole for urinary tract infections. Also in elderly diabetics using sulfonylureas, therapeutic doses of salicylates, monoamine-oxidase inhibitors and probably pro-pranolol should be co-administered with caution, including frequent blood glucose monitoring as long as necessary. Finally, the danger of refractory hypoglycemia in the newborn .proscribes the mother's use of sulfonylureas during the last month of pregnancy. Drug-induced hypoglycemia is now so relatively common that virtually every unconscious patient should be considered hypoglycemie until immediate estimation of the blood sugar level rules the condition in or out. If it is ruled in, the clinician should promptly start 10 per cent glucose by vein and plan to maintain it uninterruptedly for one or more days, with added hydrocortisone and glucagon if necessary, until persistent hyperglycemia guarantees that all drug effects have worn off.

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