Mary C. Gannon

Effect of Protein Ingestion on the Glucose and Insulin Response to a Standardized Oral Glucose Load

Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 ± 35, 83 ± 19 µU · h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 ± 33 µU · h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.

The insulin and glucose responses to meals of glucose plus various proteins in type II diabetic subjects

We previously have shown that ingested beef protein is just as potent as glucose in stimulating a rise in insulin concentration in type II diabetic patients. A synergistic effect was seen when given with glucose. Therefore, we considered it important to determine if other common dietary proteins also strongly stimulate an increase in insulin concentration when given with glucose. Seventeen type II (non-insulin-dependent) untreated diabetic subjects were given single breakfast meals consisting of 50 g glucose, or 50 g glucose plus 25 g protein in the form of lean beef, turkey, gelatin, egg white, cottage cheese, fish, or soy. The peripheral plasma concentrations of glucose, insulin, glucagon, alpha amino nitrogen, urea nitrogen, free fatty acids, and triglycerides were measured. Following ingestion of the meals containing protein, the plasma insulin concentration was increased further and remained elevated longer compared with the meal containing glucose alone. The relative area under the insulin response curve was greatest following ingestion of the meal containing cottage cheese (360%) and was least with egg white (190%) compared with that following glucose alone (100%). The glucose response was diminished following ingestion of the meals containing protein with the exception of the egg white meals. The peripheral glucagon concentration was decreased following ingestion of glucose alone and increased following all the meals containing protein. The alpha amino nitrogen concentration varied considerably. It was decreased after glucose alone, was unchanged after egg white ingestion, and was greatest after ingestion of gelatin. The free fatty acid concentration decrease was 4- to 8-fold greater after the ingestion of protein with glucose compared with ingestion of glucose alone.

Plasma glucose and insulin profiles in normal subjects ingesting diets of varying carbohydrate, fat, and protein content.

The 12-hr profiles of plasma glucose and insulin concentrations in 26 normal subjects ingesting a diet high in carbohydrate, protein, or fat have been determined. The diets were isocaloric and were given as three identical meals 4 hrs apart. In males the high carbohydrate diet resulted in glucose profiles similar to those obtained with the standard diet. In females the peak glucose concentration also was not increased but the glucose concentration remained elevated longer after each meal. In both groups the insulin curves followed the glucose curves. The post-meal glucose and insulin areas were significantly increased in the female group. The high protein diet resulted in only a small post-meal glucose rise particularly later in the day in both males and females. However, there was a sharp rise in insulin concentration after each meal. The total insulin area after each meal was nearly as great as with the standard diet. The high fat diet, which contained approximately the same carbohydrate content as the high protein diet, induced a clear increase in glucose concentration after each meal in the female group. However, the peak was progressively delayed with each meal. The insulin curves followed the glucose curves. In males a small, prolonged post-meal increase in glucose was observed after each meal. The insulin concentration increased modestly after the first meal and then remained elevated and changed little after the subsequent meals. These data help to define the glucose and insulin responses to meals varying greatly in protein, carbohydrate, and fat content and further indicate the need to consider the response of males and females separately.

Meal stimulation of cortisol secretion: A protein induced effect

Cortisol and ACTH secretion was studied in 52 healthy subjects who were fasted of fed various diets: standard, high fat, high carbohydrate, high protein. Subjects fed high protein diet (4 gm/kg body weight) showed significant increases in cortisol both at 30 and 60 min after the 1200 hr meal and 30 min after the 1600 hr meal. Increases in cortisol, of a smaller magnitude, were also seen after both the 1200 and 1600 hr meals in each of the diets with 1 gm protein/kg body weight (standard, high fat, high carbohydrate). ACTH was significantly increased following the 1200 hr and 1600 hr meals with the high protein diet. We conclude that dietary protein plays an important role in meal stimulated cortisol release.

Plasma Glucose and Insulin Response to Macronutrients in Nondiabetic and NIDDM Subjects

Information on the metabolic response in people with non-insulin-dependent diabetes mellitus (NIDDM) to ingested individual macronutrients is limited. Available information is reviewed herein. The major absorbed products of carbohydrate-containing foods are glucose, fructose, and galactose. The quantitative effect of these on the plasma glucose and insulin response is different for each. In addition, available data indicate that the glucose and particularly the insulin response is different from that in nondiabetic people. The quantitative effect of dietary proteins and fats on the circulating glucose and insulin concentrations in nondiabetic and NIDDM subjects also has been reviewed. Neither has a significant effect on the glucose concentration. Protein stimulates insulin secretion, and this is relatively more prominent in people with NIDDM. A strong synergistic interaction with glucose on insulin secretion is present, but this is absent in nondiabetic people. Ingested fat does not independently stimulate insulin secretion. However, when ingested with carbohydrate, it may have a considerable effect on the plasma glucose and/or insulin response to that carbohydrate, and the responses are different in nondiabetic and NIDDM subjects. This is probably not due to altered carbohydrate absorption. Intestinal hormones undoubtedly are playing a large role in the insulin secretory response in all of these studies, but this remains to be completely elucidated. Overall, the data indicate that the metabolic response to various foods determined in people with NIDDM may be different than that in nondiabetic people. In our opinion, much more information is required before dietary recommendations for NIDDM subjects can be made based on solid scientific data.

High-dose naltrexone therapy and dietary counseling for obesity

There is considerable evidence that antagonism of the endogenous opioids will suppress food intake in a variety of animal species. The authors report a double-blind, placebo-controlled trial of the long-acting, orally active narcotic antagonist naltrexone in the promotion of weight loss in obese male subjects who were also undergoing dietary counseling for weight reduction. Subjects received medication (naltrexone, 300 mg/day or placebo) for 8 weeks following an initial 2-week single-blind placebo phase. The results failed to demonstrate an advantage for the active drug. However, the naltrexone was associated with hepatotoxicity when used at this dosage in this population.

Regulation of hepatic glucose production and the role of gluconeogenesis in humans : is the rate of gluconeogenesis constant?

We have been interested in the metabolic effects of ingested fuels, both in normal subjects and in people with type 2 diabetes. Recently, we have become interested in the regulation of glucose production and the regulation of gluconeogenesis in particular. We are not aware of a recent comprehensive review of these topics. Therefore, we have reviewed the currently available literature.

Control of blood glucose in type 2 diabetes without weight loss by modification of diet composition

BackgroundOver the past several years our research group has taken a systematic, comprehensive approach to determining the effects on body function (hormonal and non-hormonal) of varying the amounts and types of proteins, carbohydrates and fats in the diet. We have been particularly interested in the dietary management of type 2 diabetes. Our objective has been to develop a diet for people with type 2 diabetes that does not require weight loss, oral agents, or insulin, but that still controls the blood glucose concentration. Our overall goal is to enable the person with type 2 diabetes to control their blood glucose by adjustment in the composition rather than the amount of food in their diet.MethodsThis paper is a brief summary and review of our recent diet-related research, and the rationale used in the development of diets that potentially are useful in the treatment of diabetes.ResultsWe determined that, of the carbohydrates present in the diet, absorbed glucose is largely responsible for the food-induced increase in blood glucose concentration. We also determined that dietary protein increases insulin secretion and lowers blood glucose. Fat does not significantly affect blood glucose, but can affect insulin secretion and modify the absorption of carbohydrates. Based on these data, we tested the efficacy of diets with various protein:carbohydrate:fat ratios for 5 weeks on blood glucose control in people with untreated type 2 diabetes. The results were compared to those obtained in the same subjects after 5 weeks on a control diet with a protein:carbohydrate:fat ratio of 15:55:30. A 30:40:30 ratio diet resulted in a moderate but significant decrease in 24-hour integrated glucose area and % total glycohemoglobin (%tGHb). A 30:20:50 ratio diet resulted in a 38% decrease in 24-hour glucose area, a reduction in fasting glucose to near normal and a decrease in %tGHb from 9.8% to 7.6%. The response to a 30:30:40 ratio diet was similar.ConclusionAltering the diet composition could be a patient-empowering method of improving the hyperglycemia of type 2 diabetes without weight loss or pharmacologic intervention.

The serum insulin and plasma glucose responses to milk and fruit products in Type 2 (non-insulin-dependent) diabetic patients

SummaryThe plasma glucose and serum insulin responses were determined in untreated Type 2 (non-insulin-dependent) diabetic patients following the ingestion of foods containing sucrose, glucose, fructose or lactose in portions that contained 50 g of carbohydrate. The results were compared to those obtained following the ingestion of pure fructose, sucrose, glucose, +fructose and lactose. The objectives were to determine 1) if the glucose response to naturally occurring foods could be explained by the known carbohydrate content, and 2) whether the insulin response could be explained by the glucose response. The glucose response was essentially the same whether the carbohydrate was given as a pure substance, or in the form of a naturally occurring food. The glucose response to each type of carbohydrate was that expected from the known metabolism of the constituent monosaccharides. The glucose areas following the ingestion of the foods were: Study 1: glucose 11.7, orange juice 7.3, sucrose 5.2, glucose+fructose 6.3, and fructose 0.7 mmol · h/1; Study 2: glucose 14.6, orange juice 7.3, apples 5.5, and apple juice 4.7 mmol · h/1; Study 3 : glucose 12.6, ice cream 8.1, milk 3.7, and lactose 4.1 mmol · h/1. The insulin response was greater than could be explained by the glucose response for all meals except apples. Milk was a particularly potent insulin secretagogue; the observed insulin response was approximately 5-fold greater than would be anticipated from the glucose response. In summary, the plasma glucose response to ingestion of fruits and milk products can be predicted from the constituent carbohydrate present. The serum insulin response cannot.

Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose

Our laboratory is interested in the metabolic effects of ingested proteins. As part of this research, we currently are investigating the metabolic effects of ingested individual amino acids. The objective of the current study was to determine whether leucine stimulates insulin and/or glucagon secretion and whether, when it is ingested with glucose, it modifies the glucose, insulin, or glucagon response. Thirteen healthy subjects (6 men and 7 women) were studied on 4 different occasions. Subjects were admitted to the special diagnostic and treatment unit after a 12-hour fast. They received test meals at 8:00 am. On the first occasion, they received water only. Thereafter, they received 25 g glucose or 1 mmol/kg lean body mass leucine or 1 mmol/kg lean body mass leucine plus 25 g glucose in random order. Serum leucine, glucose, insulin, glucagon, and alpha-amino nitrogen concentrations were measured at various times during a 2.5-hour period after ingestion of the test meal. The amount of leucine provided was equivalent to that present in a high-protein meal, that is, that approximately present in a 350-g steak. After leucine ingestion, the leucine concentration increased 7-fold; and the alpha-amino nitrogen concentration increased by 16%. Ingested leucine did not affect the serum glucose concentration. When leucine was ingested with glucose, it reduced the 2.5-hour glucose area response by 50%. Leucine, when ingested alone, increased the serum insulin area response modestly. However, it increased the insulin area response to glucose by an additional 66%; that is, it almost doubled the response. Ingested leucine stimulated an increase in glucagon. Ingested glucose decreased it. When ingested together, the net effect was essentially no change in glucagon area. In summary, leucine at a dose equivalent to that present in a high-protein meal, had little effect on serum glucose or insulin concentrations but did increase the glucagon concentration. When leucine was ingested with glucose, it attenuated the serum glucose response and strongly stimulated additional insulin secretion. Leucine also attenuated the decrease in glucagon expected when glucose alone is ingested. The data suggest that a rise in glucose concentration is necessary for leucine to stimulate significant insulin secretion. This in turn reduces the glucose response to ingested glucose.