No abstract

Ethyl alcohol which has been reported to be without effect on insulin secretion apparently modifies beta-cell function nevertheless, as indicated by the plasma insulin responses to glucose loading after prior administration of alcohol. Glucose was injected intravenously in nine young adults on three separate occasions at intervals of at least two weeks. During the twelve hours preceding each test the subjects received ethanol either by mouth or by vein or, as a control, no ethanol. Plasma insulin and glucose concentrations were not noticeably affected by the ethanol alone but alcohol pretreatment was followed in all instances by heightened plasma insulin responses to the glycemic pulse stimulus and by accelerated rates of plasma glucose disappearance. The mean plasma insulin response was increased 50 per cent by the alcohol, irrespective of the route of administration. Unlike recognized insulin secretogogues, therefore, ethanol appears to augment insulin secretion only on demand. The route of administration appeared not to be a factor in determining the magnitude of the alcohol effect. Other alcohol effects included blunting of the plasma pyruvate and exaggeration of the plasma lactate elevations after glucose.

Gatifloxacin was well tolerated in patients with NIDDM controlled by diet and exercise. It had no significant effect on glucose homeostasis, beta-cell function, or long-term fasting serum glucose levels, but it did cause a brief increase in serum insulin levels.

. P.R., L.J., and R.R. are members of the Novo Nordisk Diabetes Expert Advisory Board, and P.R., L.J., S.S., and R.R. are recipients of Novo Nordisk honoraria.Abbreviations: ECG, electrocardiogram; FPG, fasting plasma glucose. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Repaglinide/Troglitazone Combination Therapy Improved glycemic control in type 2 diabetes O R I G I N A L A R T I C L EOBJECTIVE -This multicenter open-label clinical trial compared the efficacy and safety of repaglinide/troglitazone combination therapy, repaglinide monotherapy, and troglitazone monotherapy in type 2 diabetes that had been inadequately controlled by sulfonylureas, acarbose, or metformin alone.RESEARCH DESIGN AND METHODS -Patients with type 2 diabetes (n = 256) who had inadequate glycemic control (HbA 1c Ն7.0%) during previous monotherapy were randomly assigned to receive repaglinide (0.5-4.0 mg at meals), troglitazone (200-600 mg once daily), or a combination of repaglinide (1-4 mg at meals) and troglitazone (200-600 mg once daily). After a 4-6 week washout period, the trial assessed 22 weeks of treatment: 3 weeks (weeks 0-2) of forced titration, 11 weeks of fixed-dose treatment (weeks 3-13), and 8 weeks (weeks 14-21) of titration to maximum dose. E m e r g i n g T r e a t m e n t s a n d T e c h n o l o g i e s 980DIABETES CARE, VOLUME 23, NUMBER 7, JULY 2000 Study designForced titration: weeks 0-2. After a 4-to 6-week washout period when previous drug therapy was discontinued, patients received 0.5 mg repaglinide 0-30 min before each meal, or 200 mg troglitazone once daily, or a combination of both repaglinide (0.5 mg at meals) and troglitazone (200 mg once daily). The dose of repaglinide was increased to 1.0 mg at meals after 1 week (after week 0) and was further increased to 2.0 mg after 2 weeks of treatment. The dose of troglitazone was increased to 400 mg once daily after 2 weeks of treatment. Patients in the combination therapy group received 1.0 mg repaglinide and 200 mg troglitazone after 1 week (after week 0), 2.0 mg repaglinide and 200 mg troglitazone after 2 weeks, and 2.0 mg repaglinide and 400 mg troglitazone at the end of third week of treatment. Fixed-dose treatment: weeks 3-13. The dosage levels of all treatments were then maintained for 11 weeks from the beginning of week 3 until the end of week 13. However, the clinical trial protocol called for a reduction in dosage in the event of persistent levels of fasting plasma glucose (FPG) Ͻ80 mg/dl and/or repeated major hypoglycemia. Such dose reduction was to be achieved by reversing the last step of the dose increment schedule. FPG and HbA 1c levels were measured at weeks 0, 10, and 14, and circulating liver transaminase levels were measured at weeks 0, 4, 7, 10, and 14. Titration to maximum dose: weeks 14-21. After 14 weeks of treatment, FPG values were used to assess the need for further escalation of the dose. If the FPG value was Ͼ120 mg/dl, then the patient was titrated to...

The ingestion of protein by normal human subjects has been shown recently to represent a stimulus to the secretion of insulin. This response is probably related to the postprandial rise in plasma amino acid concentration. Since disordered protein synthesis may contribute to the pathogenesis of diabetes and its complications, the insulin response to ingested protein (casein or gelatin, 50-100 gm.) was compared in twenty-eight normals and ten maturity-onset diabetics. Insulin response (microunits-minutes, μU.-min.) was considered to be the area included by that portion of the plasma insulin response curve above projected basal insulin secretion. Following protein ingestion the diabetics showed a mean insulin response (± S.E.M.) of 3,425 ± 367 μU.-min., compared with 1,005 ± 136 in the normals, a 3.4-fold difference (p < 0.01). In neither group were there significant or consistent changes in plasma glucose concentration. The fall in free fatty acids was comparable and no difference was seen in the plasma amino acid nitrogen curves. These data indicate that the insulin response to ingested protein is excessive in diabetes. The mechanism of the hyperresponse would seem to lie within the beta cell since no abnormality of the presumed amino acid stimulus was demonstrated.

The effect of varying the size of a meal on plasma insulin was determined in eight normal male adults. The effect of consuming one half of a meal at 0 time and one half at two hours later was also studied. Each subject was studied on four days, one day when he consumed a whole meal (580 calories) of natural foodstuffs; one day, one-half the meal; one day, one quarter of the meal, and one day when he consumed one half the meal at 0 time and the remainder two hours later. When fractions of the meals were ingested, all ingredients were decreased proportionately. As meal size was increased, a log-dose relationship was observed to characterize the comparison of meal size ingested to plasma insulin response. When on the fourth day the subjects consumed the meal in fractions, the mean sum of the plasma insulin responses was identical to that observed when the meal was eaten at one time. The results suggest that over a four-hour period, the plasma insulin response is a function of the magnitude of the load of calories requiring disposition and that the response does not appear to be influenced by the frequency with which the calories are ingested. DIABETES 17: 72-75, February, 1968.

No abstract

Both protein ingestion and amino acid infusion are known to stimulate insulin secretion. The mechanism of this response has been attributed to increased plasma amino acid concentration. The present studies were undertaken to determine whether this-secretory response is due to a direct effect of amino acids on the islet cells or whether it is mediated through some other indirect mechanism. Accordingly, pancreatic infusion studies were conducted to help resolve this question.Casein hydrolysate (1 gm.) infused into the pancreaticoduodenal artery of dogs for one-half hour provoked an immediate secretion of insulin into the portal vein. Femoral arterial insulin concentration also rose within five minutes, although hyperglycemia was not observed until the end of the infusion. An insulin response of similar magnitude was achieved by pancreatic glucose infusion (1 gm.). Simultaneous administration of epinephrine (30 /ig.) inhibited the insulin responses to both glucose and amino acid. Combined infusion of casein hydrolysate and glucose (0.5 gm. each) produced a greater insulin response than the sum of the individual responses, suggesting glucose-amino acid synergism. Intraportal infusion of casein hydrolysate produced no significant insulin response in either portal venous or femoral arterial plasma.These studies surest t W thp insulin response associated with ingested or parenteral protein represents a direct amino acid effect on the islets of