Robert Metz

Potentiation of the plasma insulin response to glucose by prior administration of alcohol. An apparent islet-priming effect.

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.

Long-term metabolic control with insulin pump therapy. Report of experience with 127 patients.

To determine the long-term efficacy of insulin-pump therapy, we analyzed trends in glycosylated hemoglobin concentrations in 127 patients with Type I diabetes using insulin pumps for periods ranging from 13 to 47 months. In the first year of pump therapy the average glycosylated hemoglobin concentration improved in 83 per cent of the patients, as compared with the value before pump therapy. Although only 11 of the 127 subjects had normal glycosylated hemoglobin values before pump therapy, 33 had a normal average value during the first full year of pump use (P = 0.0001). This favorable trend persisted for the three-year duration of the study. Seventeen of the 19 patients who subsequently discontinued insulin-pump therapy had improved glycosylated hemoglobin values during the period of pump use. Eleven of the 19 patients remained available for follow-up study; the glycosylated hemoglobin concentration became worse in 7 when they returned to conventional treatment. We conclude that the improvement in metabolic control repeatedly demonstrated in short-term studies with the insulin pump can be maintained for a period of years.

Differential Plasma Insulin Response to Glucose and Glucagon Stimulation Following Ethanol Priming

The early phase of the insulin secretory response to glucose may not be derived from the total pool of stored insulin, but possibly from a specific and relatively small fraction in a state or locus necessary for its immediate release. In an attempt to deplete this hypothetical fraction, and thereby to support the concept of its existence and obtain an estimate of its size under different circumstances, normal and mildly diabetic subjects were given a series of three large glucose loads followed by glucagon, with and without alcohol “priming”. Results indicate that repetitive glucose or glucagon challenges over a two-hour period failed to exhaust the supply of immediately releasable insulin in either group of subjects as judged by the increments in plasma insulin during the first few minutes after each challenge. Alcohol pretreatment resulted in a larger early insulin secretory response to the first of three glucose loads, but a decreasing response to the subsequent two, possibly indicating that the initially augmented secretory response had resulted in depletion of a finite supply of immediately available insulin. An unexpected finding was the inhibitory effect of alcohol on glucagon-induced insulin release, in direct contrast to its effect when glucose is the insulinogogue, suggesting that glucose and glucagon exert their effects throughdifferent mechanisms or on different fractions of the insulin pool.

Glucose Tolerance, Plasma Insulin, and Free Fatty Acids in Elderly Subjects

Excerpt The older an individual on whom a glucose tolerance test is performed, the more likely will the result be abnormal, as judged by standard criteria (1-9). The evidence suggests that this tre...

Flocculation and Loss of Potency of Human NPH Insulin

In late 1986, several vials of Humulin N (NPH human insulin, recombinant DNA origin) came to our attention because of a clumped, white coating on the inside of the vials. To determine the frequency of this phenomenon, we surveyed 100 consecutive patients who used Humulin N. Ten patients had encountered 21 vials of flocculated insulin in the previous 12 mo, reflecting an incidence of 1 per 72 vials. Insulin drawn from affected vials was markedly reduced in potency: 20.9 ± 3.4 U/ml vs. the labeled potency of 100 U/ml. Several patients reporting flocculated insulin, including one hospitalized with ketoacidosis, experienced unusual and unexplained elevation in blood glucose concentration for several days before flocculation was observed. Patients who use NPH human insulin should be aware of this phenomenon and carefully inspect their vials for evidence of insulin precipitation before each injection.

The effect of glucagon on fructose metabolism in diabetic and non-diabetic human beings

Abstract Glucagon substantially modified the plasma pyruvate and lactate responses to a fructose load in diabetic and non-diabetic human subjects. Addition of glucagon (60 μg. per minute for 30 minutes) at the 60th minute of a fructose infusion was followed by a prompt and complete reversal of the elevation of plasma pyruvate produced by the fructose alone. Lactate concentrations also decreased after glucagon, but the change was much less pronounced, so that the lactate-pyruvate ratio increased. These results appear to indicate that glucagon thwarted hepatic utilization of the carbohydrate load and concomitantly altered intra-hepatic redox potential.