Glucose Response Area Research Articles

Effect of Orally Administered Phenylalanine with and without Glucose on Insulin, Glucagon and Glucose Concentrations

As part of our studies of the metabolic effects of ingested proteins, we are currently investigating the effects of ingestion of individual amino acids. The objective of the present study was to determine whether ingested phenylalanine stimulates insulin and/or glucagon secretion, and if phenylalanine ingested with glucose modifies the insulin, glucagon or glucose response to the ingested glucose. Six healthy subjects were tested on 4 separate occasions. Plasma phenylalanine, glucose, insulin, glucagon, and total alpha amino nitrogen (AAN) (i.e., total amino acids) concentrations were measured at various times during a 2.5 h period after ingestion of 1 mmol phenylalanine/kg lean body mass, 25 g glucose, 1 mmol phenylalanine/kg lean body mass+25 g glucose, or water only, given in random order. Following phenylalanine ingestion, the circulating phenylalanine concentration increased approximately 14 fold and remained elevated for the duration of the experiment. Glucagon and AAN increased, insulin increased modestly, and glucose was unchanged when compared to water ingestion. When glucose was ingested with phenylalanine, the circulating phenylalanine, glucagon, AAN, and insulin area responses were approximately the sum of the responses to phenylalanine alone and glucose alone. However, the plasma glucose area response was decreased 66% when phenylalanine was co-ingested with glucose. In summary, phenylalanine in an amount moderately greater than that in a large protein meal stimulates an increase in insulin and glucagon concentration. It markedly attenuates the glucose-induced rise in plasma glucose when ingested with glucose.

The relationship between 24-hour integrated glucose concentrations and % glycohemoglobin

Since glycohemoglobin values are widely used clinically as a surrogate for average glucose concentration over an extended period of time, we decided to determine the actual relationship between 24-hour integrated glucose values and percent total glycohemoglobin (%tGHb) in cohorts of people with and without diabetes. In 48 people without known diabetes with known stability of fasting glucose over a 1-year period of time, the calculated 24-hour integrated glucose concentration was compared with their %tGHb. In 15 normal young medical students, the glucose area response was determined from 46 venous blood samples obtained during a 24-hour period and compared with their %tGHb. In 18 people with type 2 diabetes, interstitial glucose concentrations were monitored using the Continuous Glucose Monitoring System (Medtronic MiniMed, Inc., Sylmar, Calif) for 3 days at 20-day intervals over 100 days. %tGHb was performed at 20-day intervals simultaneously. In 29 people with untreated type 2 diabetes, glucose area response was determined from 46 venous blood samples obtained during a 24-hour period and compared with their %tGHb after being on a standardized diet provided to the subjects for at least 5 weeks. The %tGHb and 24-hour profiles were stable. There was an excellent correlation between the mean 24-hour glucose concentration and the %tGHb among subjects with diabetes. The correlation was poor among subjects without diabetes. The relationship was curvilinear when plotted as a single group. Alternatively when data from subjects with or without diabetes were plotted separately, the slopes were identical but the y-intercepts were different. The relationship between the mean glucose concentration integrated over an extended period of time and the %tGHb is not linear. The reason for this nonlinearity remains to be determined. This non-linearity needs to be considered in the clinical interpretation of %tGHb (and probably HbA(1c)) in reference to glucose values.

The metabolic response to ingestion of proline with and without glucose

Ingested protein results in an increase in circulating insulin and glucagon concentrations and no change, or a slight decrease, in circulating glucose. In subjects with type 2 diabetes, when protein is ingested with glucose, insulin is further increased and the glucose rise is less than when glucose is ingested alone. Presumably these effects are due to the amino acids present in the proteins. The effects of individual amino acids, ingested in physiologic amounts, with or without glucose, have not been determined. Therefore, we have begun a systematic study of the response to ingested amino acids. Eight young, non-obese, subjects (4 men, 4 women) ingested 1 mmol proline/kg lean body mass, 25 g glucose, 25 g glucose + 1 mmol proline/kg lean body mass or water only on 4 separate occasions at 8 am. Blood was obtained before and after ingestion of the test meal over the following 150 minutes. Proline ingestion resulted in a 13-fold increase in the plasma proline concentration. This was decreased by 50% when glucose was ingested with proline. Proline alone had little effect on glucose, insulin, or glucagon concentrations. However, ingestion of proline with glucose resulted in a 23% attenuation of the glucose area response and no change in insulin response compared with the response to that of glucose alone. A glucose-stimulated decrease in glucagon was further facilitated by proline. Ingested proline is readily absorbed. It reduces the glucose-induced increase in glucose concentration in the presence of an unchanged insulin and a decreased glucagon response.

An increase in dietary protein improves the blood glucose response in persons with type 2 diabetes

In single-meal studies, dietary protein does not result in an increase in glucose concentrations in persons with or without type 2 diabetes, even though the resulting amino acids can be used for gluconeogenesis. The metabolic effects of a high-protein diet were compared with those of the prototypical healthy (control) diet, which is currently recommended by several scientific organizations. The metabolic effects of both diets, consumed for 5 wk each (separated by a 2-5-wk washout period), were studied in 12 subjects with untreated type 2 diabetes. The ratio of protein to carbohydrate to fat was 30:40:30 in the high-protein diet and 15:55:30 in the control diet. The subjects remained weight-stable during the study. With the fasting glucose concentration used as a baseline from which to determine the area under the curve, the high-protein diet resulted in a 40% decrease in the mean 24-h integrated glucose area response. Glycated hemoglobin decreased 0.8% and 0.3% after 5 wk of the high-protein and control diets, respectively; the difference was significant (P < 0.05). The rate of change over time was also significantly greater after the high-protein diet than after the control diet (P < 0.001). Fasting triacylglycerol was significantly lower after the high-protein diet than after the control diet. Insulin, C-peptide, and free fatty acid concentrations were not significantly different after the 2 diets. A high-protein diet lowers blood glucose postprandially in persons with type 2 diabetes and improves overall glucose control. However, longer-term studies are necessary to determine the total magnitude of response, possible adverse effects, and the long-term acceptability of the diet.

The metabolic response to ingested glycine

The metabolic effects of dietary protein are complex. In persons with type 2 diabetes, protein ingestion results in little or no increase in plasma glucose concentrations but a stimulation of insulin and glucagon secretion. Furthermore, when protein is ingested with glucose, a synergistic effect on insulin secretion is observed. The most potent protein is gelatin, which consists of 30% glycine residues. The objective of the present study was to determine whether glycine per se stimulates insulin secretion or reduces the glucose response when ingested with glucose. Nine healthy subjects were tested on 4 separate occasions. Plasma glucose, insulin, glucagon, and glycine concentrations were measured at various times during a 2-h period after the ingestion of 1 mmol glycine/kg lean body mass, 25 g glucose, 1 mmol glycine/kg lean body mass + 25 g glucose, or water only, given in random order. Plasma concentrations of glycine and glucagon were elevated after the ingestion of glycine, as expected. The serum insulin concentration also was slightly elevated after the ingestion of glycine alone. When glycine was ingested with glucose, the plasma glucose area response was attenuated by > 50% compared with the response after the ingestion of glucose alone. The dynamics of the insulin response after the ingestion of glycine plus glucose were modestly different from those after the ingestion of glucose alone, but the area response was not significantly different. The data are compatible with the hypothesis that oral glycine stimulates the secretion of a gut hormone that potentiates the effect of insulin on glucose removal from the circulation.

Alcohol and postexercise metabolic responses in type 2 diabetes

The objective was to investigate the impact of the combination of exercise and alcohol on the metabolic response in nonfasting and fasting type 2 diabetic subjects. In part 1, 12 untrained middle-aged type 2 diabetic subjects participated on 3 test days. On each day, they ingested a light meal (1,824 kJ) containing 48 energy percent (E%) carbohydrate, 38 E% fat, and 14 E% protein. The meal was followed by either (A) rest or (B) 30 minutes of exercise (40% of maximum O 2 consumption [VO 2max]) or (C) taken with alcohol (0.4 g/kg body weight) followed by 30 minutes of exercise (40% of VO 2max). In part 2, 11 untrained middle-aged type 2 diabetic subjects participated on 4 test days without a meal. The subjects were either (A) resting, (B) drinking alcohol (0.4 g/kg body weight), (C) exercising 30 minutes (40% of VO 2max), or (D) drinking alcohol (0.4 g/kg body weight) and exercising 30 minutes (40% of VO 2max). On each test day, regular blood samples were drawn for 4 hours for analysis of glucose, insulin, lactate, triglycerides, nonesterified fatty acid (NEFA), and ethanol. Comparing exercise and rest following a light meal (part 1, no change (7%) occurred in the plasma glucose response area (642 ± 119 v 724 ± 109 mmol · L −1 · 240 min, NS). However, it was significantly reduced (by 27%) in response to exercise and alcohol (509 ± 98 v 724 ± 109 mmol · L −1 × 240 min; P = .03). Similar serum insulin response areas were obtained. After exercise and alcohol, plasma lactate increased compared with the resting state (2.2 ± 0.2 v 1.6 ± 0.1 mmol · L −1, P = .004) and with exercise alone (2.2 ± 0.2 v 1.8 ± 0.2 mmol ± L −1, P = .04). Serum NEFAs were significantly reduced by exercise and alcohol compared with the resting state (0.50 ± 0.04 v 0.65 ± 0.06 mmol · L −1, P = .008) and with exercise alone (0.50 ± 0.04 v 0.61 ± 0.05 mmol · L −1, P = .02). Similar serum triglycerides were found. During the fasting state (part 2), similar plasma glucose response areas were obtained in the four situations. The insulin response area to exercise and alcohol increased significantly compared with the resting state (3,325 ± 744 v 882 ± 295 pmol · L −1 × 240 min, P = .02) and with exercise alone (3,325 ± 744 v 1,328 ± 422 pmol · L −1 × 240 min, P = .007). No difference was found compared with alcohol alone. Plasma lactate was higher after alcohol intake versus the resting state (1.9 ± 0.1 v 1.3 ± 0.1 mmol · L −1, P = .003), as well as after exercise and alcohol (1.9 ± 0.1 v 1.3 ± 0.1 mmol · L −1, P = .01). After exercise and alcohol serum NEFAs were significantly reduced compared with the resting state (0.43 ± 0.02 v 0.64 ± 0.02 mmol · L −1, P < .001), alcohol alone (0.43 ± 0.02 v 0.51 ± 0.02 mmol · L −1, P < .001), and exercise alone (0.43 ± 0.02 v 0.64 ± 0.02 mmol · L −1, P < .001). Serum triglycerides were similar in the four situations. We conclude that moderate exercise with or without moderate alcohol intake does not cause acute hypoglycemia either after a light meal or in the fasting state in untrained overweight type 2 diabetic subjects.

Similarity of relative glycaemic but not relative insulinaemic responses in normal, IGT and diabetic subjects

To determine the validity of measuring relative plasma glucose and insulin responses of foods, we studied 4 subject groups: 10 lean normal, 9 obese normal, 9 with impaired glucose tolerance (IGT) and 8 with mild diabetes (DM). Overnight fasted subjects consumed either 75g oral glucose or 50g carbohydrate from a standard test meal. Each subject repeated each test 4 times on separate days using a randomized block design. The mean of the incremental plasma glucose and insulin response areas for each subject's 4 standard test meals were expressed as a % of the respective mean for the 4 glucose tests and the resulting values termed relative responses. Relative glucose responses did not differ significantly in lean (51±6), obese (41±4), IGT (52±4) and DM (54±2) subjects. However, there was heterogeneity of mean relative insulin responses (p=0.0003) with the values in obese normal (50±5), IGT (69±5) and DM (84±7) subjects being significantly different from each other. The mean in lean normal subjects, 61±3, was significantly less than DM, but no different from obese and IGT. These results support the concept and clinical utility of the glycaemic index as a measure of the blood glucose raising potential of foods that is valid in normal and glucose intolerant subjects. However, they suggest that the insulinaemic index is less clinically useful because it varies in different groups of subjects.

Decreased Glucose Response to Insulin is Maximal Within 24 Hours of Somatotropin Injection in Growing Pigs

Porcine somatotropin (pST) administration reduces the sensitivity of pigs to insulin, and after several days of treatment, it alters baseline circulating concentrations of pST, insulin, glucose, and other metabolites. The length of time required to develop this reduction in whole-body insulin sensitivity has not been established. To investigate this, eight castrate pigs received daily injections of either recombinant pST (120 μg/kg BW) or excipient. Intravenous insulin tolerance tests (1.0 μg/kg BW) were done before the first pST injection (Day 0) and on Day l, 3, 5, and 8 of pST treatment. Control animals had insulin tolerance tests on Day 0 and again on Day 8 of treatment. By Day 8, the glucose response to the insulin tolerance tests in pST-treated pigs was 45% of the response of the control group (P < 0.01). Glucose response areas between Day l, 3, 5, and 8 of pST treatment were not different (P > 0.10). The maximum effect of pST on glucose response to insulin was achieved by Day 1. Therefore, factors responsible for the development of reduced whole-body insulin sensitivity in pST-treated pigs are fully expressed within 21 hr of the initial pST treatment.

Antihypertensive agent moxonidine enhances muscle glucose transport in insulin-resistant rats.

The sympatholytic antihypertensive agent moxonidine, a centrally acting selective I1-imidazoline receptor modulator (putative agonist), may be beneficial in hypertensive patients with insulin resistance. In the present study, the effects of chronic in vivo moxonidine treatment of obese Zucker rats--a model of severe glucose intolerance, hyperinsulinemia and insulin resistance, and dyslipidemia--on whole-body glucose tolerance, plasma lipids, and insulin-stimulated skeletal muscle glucose transport activity (2-deoxyglucose uptake) were investigated. Moxonidine was administered by gavage for 21 consecutive days at 2, 6, or 10 mg/kg body weight. Body weights in control and moxonidine-treated groups were matched, except at the highest dose, at which final body weight was 17% lower in the moxonidine-treated animals compared with controls. The moxonidine-treated (6 and 10 mg/kg) obese animals had significantly lower fasting plasma levels of insulin (17% and 19%, respectively) and free fatty acids (36% and 28%, respectively), whereas plasma glucose was not altered. During an oral glucose tolerance test, the glucose response (area under the curve) was 47% and 67% lower, respectively, in the two highest moxonidine-treated obese groups. Moreover, glucose transport activity in the isolated epitrochlearis muscle stimulated by a maximally effective insulin dose (13.3 nmol/L) was 39% and 70% greater in the 6 and 10 mg/kg moxonidine-treated groups, respectively (P<.05 for all effects). No significant alterations in muscle glucose transport were elicited by 2 mg/kg moxonidine. These findings indicate that in the severely insulin-resistant and dyslipidemic obese Zucker rat, chronic in vivo treatment with moxonidine can significantly improve, in a dose-dependent manner, whole-body glucose tolerance, possibly as a result of enhanced insulin-stimulated skeletal muscle glucose transport activity and reduced circulating free fatty acids.

Effect of Exercise Intensity on Glucose and Insulin Metabolism in Obese Individuals and Obese NIDDM Patients

The primary purpose of this study was to evaluate the acute effect of exercise of differing intensity on plasma glucose and insulin responses to an oral glucose challenge. Six obese men and six obese men with NIDDM of similar age, weight, percentage body fat, and VO2peak participated in the study. Each subject underwent two 7-day exercise programs in a counterbalanced order at 2-week intervals. During each 7-day exercise period, the subjects cycled every day at a power output corresponding to 50% VO2peak for 70 min or 70% VO2peak for 50 min. Muscle glycogen utilization was estimated during exercise on day 7 using a [3H]glucose infusion technique in conjunction with indirect calorimetry. During the day before and after each 7-day exercise period, a 3-h oral glucose tolerance test (OGTT) was administered after a 12-h overnight fast. The average caloric expenditure did not differ between exercise at 50 and 70% VO2peak in both obese and obese NIDDM subjects. However, the carbohydrate oxidation was higher (P < 0.05) during exercise at 70 than 50% VO2peak in obese subjects (77 +/- 5 vs. 68 +/- 6 g) and obese NIDDM subjects (70 +/- 4 vs. 58 +/- 6 g). Muscle glycogen utilization was also higher (P < 0.05) during exercise at 70 than 50% VO2peak in obese subjects (59 +/- 9 vs. 30 +/- 7 g) and in obese NIDDM subjects (48 +/- 5 vs. 24 +/- 5 g). In obese subjects, plasma glucose response area during the OGTT did not change after 7 days of exercise at either 50 or 70% VO2peak. Plasma insulin response area during the OGTT also did not change after 7 days of exercise at 50% VO2peak. However, plasma insulin response area was reduced (P < 0.05) after 7 days of exercise at 70% VO2peak (9,644 +/- 1,783 vs 7,538 +/- 1,522 microU.ml-1.180 min-1). In obese NIDDM subjects, both plasma glucose and insulin response areas during the OGTT did not decrease after 7 days of exercise at either 50 or 70% VO2peak. It is concluded that the exercise-induced improvement in insulin sensitivity is influenced by exercise intensity in obese individuals. The improved insulin sensitivity after 7 days of exercise at 70% VO2peak in obese individuals may be related to greater muscle glycogen utilization during exercise. The lack of improvement in glucose tolerance and insulin sensitivity after 7 days of exercise at either 50 or 70% VO2peak in obese NIDDM patients may be due to the fact that the NIDDM patients selected in the present study were relatively hypoinsulinemic.

Differential effects of saturated and monounsaturated fat on blood glucose and insulin responses in subjects with non-insulin-dependent diabetes mellitus

To compare the metabolic effect of coingestion of saturated and monounsaturated fats with potato, 12 subjects with non-insulin-dependent diabetes mellitus (NIDDM) received 300 g mashed potato alone or in combination with 40 g olive oil, 80 g olive oil, 50 g butter, or 100 g butter, respectively. The blood glucose response area to potatoes with 100 g butter (448 +/- 68 mmol.240 min/L) was significantly lower than after the four other meals: 596 +/- 63 (potato alone), 649 +/- 82 (potato + 40 g olive oil), 587 +/- 80 (potato + 50 g butter), and 604 +/- 81 (potato + 80 g olive oil) nmol.240 min/L, P < 0.05, respectively. The insulin response was significantly increased by adding 50 and 100 g butter, whereas addition of 40 and 80 g olive oil had no effect. The fatty acid concentration was higher when 100 g butter was added to the potato meal than when it was not (0.67 +/- 0.05 compared with 0.48 +/- 0.07 mmol/L, P < 0.05). Fatty acid concentrations were similar to those found for the other meals. The triacylglycerol response increased in a dose-dependent manner with the fat content of the meals irrespective of the type of fat. We conclude that butter increases the insulin response more than does olive oil, and large amounts of butter also increase fatty acid and triacylglycerol concentrations.

Effect of Added Fat on the Plasma Glucose and Insulin Response to Ingested Potato Given in Various Combinations as Two Meals in Normal Individuals

In normal subjects, ingestion of fat with potato in a morning meal resulted in a decrease in the glucose response. Therefore, we wished to determine whether a fat-induced decrease in blood glucose also would be observed after a second identical meal. In addition, we were interested in determining if fat ingestion with a morning meal would have an effect on the blood glucose and insulin responses to a second meal not containing fat. Nine healthy male subjects ingested two meals consisting of an amount of potato containing 50 g carbohydrate, either alone or with 50 g fat as butter. The meals were served in four combinations as follows: 1) potato for the first meal, potato for the second meal; 2) potato for the first meal, potato with fat for the second meal; 3) potato with fat for the first meal, potato for the second meal; and 4) potato with fat for the first meal, potato with fat for the second meal. Meals were ingested at 8:00 A.M. and noon. Plasma glucose and C-peptide, serum insulin, triglyceride, and free fatty acid (FFA) concentrations were determined over an 8-h period. The integrated area responses to the meals were quantified over the subsequent 4-h period using the fasting value or the noon value as baseline for the first and second meals, respectively. When the first meal contained potato only, the glucose area response to the second meal was significantly less when the second meal contained fat. However, fat ingestion had no effect on the glucose area response to the second meal when fat was present in the first meal. The insulin area responses to the first and second meals were similar after ingestion of potato or potato with fat. However, the insulin response to the second meal always was less than that to the first meal. The C-peptide area responses after ingestion of the second meal also were all higher than those after the first meal. The triglyceride area responses were slightly negative after ingestion of potato alone in the first meal. When fat was ingested, they were positive. When the first meal contained fat but the second meal did not, there was a rise in triglyceride concentration after the second meal as well as after the first meal. That is, a rise occurred without ingestion of fat with the second meal. If fat was present in the second meal the rise was even greater. The FFA area responses were similar to the triglyceride area responses. When fat was ingested with carbohydrate in either the first or second meal, the glucose area response was decreased. However, when both meals contained fat, a decrease in the glucose area response did not occur with the second meal. The glucose area responses all were greater after the second meal compared with those after the first meal, i.e., the opposite of a Staub-Traugott effect was observed. The insulin area responses to the first and second meals were similar whether fat was ingested or not.

The differential effects of body fat distribution on insulin and glucose metabolism during pregnancy

Objective: Our purpose was to investigate whether maternal obesity, or more specifically body fat distribution, is associated with alterations in carbohydrate metabolism during pregnancy.Study Design: A longitudal study of oral glucose tolerance tests, insulin, C peptide, and glucagon levels during each trimester and post partum was undertaken in nine lean and 14 obese women. Obese women were divided into lower body obese (n = 6, waist/hip ratio < 0.9) and upper body obese (n = 8, waist/hip ratio ≥0.9).Results: Fasting blood glucose levels declined with advancing gestation only in lean subjects. Upper body obese women demonstrated maximal glucose response and insulin area under the curve by the second trimester, whereas lean and lower body obese women did not until the third trimester. Insulin areas were significantly elevated in upper body obese compared with lower body obese women (second trimester, p < 0.01; third trimester, p < 0.03; post partum p < 0.05). In contrast, C peptide levels were similar in obese subgroups and were significantly elevated only when compared with those of lean women. C peptide/insulin molar ratios were lower in upper body obese women during the second trimester (4.3 ± 0.8) and third trimester (4.2 ± 0.7) compared with lean (6.5 ± 1.3, 6.7 ± 0.5) and lower body obese women (7.9 ± 1.4, 6.5 ± 1.4) (p < 0.01). A significant relationship between waist/hip ratio and glucose level (r = 0.70, p < 0.004) and insulin areas (r = 0.76, p < 0.001) was present in late pregnancy in obese subjects.Conclusions: Relative hyperinsulinemia and earlier maximal glucose response in upper body obese women suggests that body fat distribution may explain the metabolic heterogeneity present in obese women during pregnancy. Body fat topography may serve as a potential marker for the early development of carbohydrate intolerance during pregnancy.

Effects of Postprandial Exercise on Glycemic Response in IDDM Subjects: Studies at constant insulinemia

To determine the influence of postprandial exercise on blood glucose responses in insulin-dependent diabetes mellitus (IDDM) subjects. Two identical test meals were served with a 7-day interval. On one occasion, a 30-min cycle exercise was performed 15 min after the meal. Patients had achieved normoglycemia by means of an artificial pancreas (Biostator) before the meals, which also ensured constant insulin infusion in the study periods. Seven IDDM subjects attending the outpatient clinic at Aarhus Kommunehospital were studied. The 30 min of cycling reduced postprandial blood glucose response areas by 34 +/- 12% (P < 0.01) from 638 +/- 30 to 492 +/- 61 mmol/l x 180 min (P < 0.03), whereas similar peak blood glucose values were found (13.7 +/- 0.3 vs. 12.0 +/- 1.3 mmol/l). Thirty minutes of moderate exercise done postprandially reduces the blood glucose response to 50 g carbohydrate by about one-third.

Effect of fixed versus weight-adjusted dose of oral glucose on plasma glucose, insulin and FFA responses: Implications for the design of postprandial studies

To see whether fixed or weight-adjusted doses of oral carbohydrate gave more reproducible postprandial responses, 7 non-obese subjects (44.6–88.0kg) took 50g, 80g, 0.7g/kg and 1.12g/kg glucose on separate days in random order, with blood samples taken at intervals over the next 240min. The incremental areas under the plasma glucose and insulin curves for the 2 low glucose doses (0.7g/kg and 50g) were similar to each other and significantly less than those for the high doses (1.12g/kg and 80g). The high doses of glucose suppressed plasma FFA levels to a lower level for a longer time than the small doses, but there was no significant difference in plasma FFA at 240min. The coefficients of variation of the glucose response areas were similar for the fixed (27%, 32%) and weight-adjusted glucose doses (29%, 30%). Insulin responses were more variable for fixed (36%, 54%) than weight-adjusted doses (26%, 25%), but the FFA level at 240min was more variable for the weight-adjusted (53%, 42%) than the fixed doses (32%, 31%). Thus, in designing experiments to study postprandial responses, the choice of fixed or weight-adjusted doses of oral carbohydrate may depend upon the metabolite of primary interest.

Effects of glucose, galactose, and lactose ingestion on the plasma glucose and insulin response in persons with non-insulin-dependent diabetes mellitus

Galactose usually is ingested as lactose, which is composed of equimolar amounts of glucose and galactose. The contribution of galactose to the increase in glucose and insulin levels following ingestion of equimolar amounts of galactose and glucose, or lactose, has not been reported in people with non-insulin-dependent diabetes mellitus (NIDDM). Therefore, we studied the effects of galactose ingestion alone, as well as with glucose either independently or in the form of lactose, in subjects with untreated NIDDM. Eight male subjects with untreated NIDDM ingested 25 g glucose, 25 g galactose with or without 25 g glucose, or 50 g lactose as a breakfast meal in random sequence. They also received 50 g glucose on two occasions as a reference. Water only was given as a control meal. Plasma galactose, glucose, glucagon, α-amino nitrogen (AAN), nonesterified fatty acids (NEFA), and serum insulin and C-peptide concentrations were determined over a 5-hour period. The integrated area responses were quantified over the 5-hour period using the water control as a baseline. Following ingestion of 25 g galactose, the maximal increase in plasma galactose concentration was 1 mmol/L. The mean maximal increases in plasma galactose concentration following ingestion of 25 g galactose + 25 g glucose or following 50-g lactose meals were similar and were only 12% of that following ingestion of galactose alone ( P < .05). The mean galactose area response over the water control for the 25-g galactose meal was 0.95 ± 0.31 mmol · h/L. That following ingestion of 25 g glucose + 25 g galactose or following the 50-g lactose meal was 0.17 ± 0.07 and 0.13 ± 0.05 mmol · h/L, respectively. Following ingestion of 25-g or 50-g glucose meals, the galactose area responses increased only slightly. The mean glucose area response following the 50-g glucose meals was 14.8 ± 2.5 mmol · h/L. Glucose area responses following ingestion of 25 g galactose, 25 g glucose, 25 g glucose + 25 g galactose, and 50 g lactose were 11%, 49%, 54%, and 60% of that observed following ingestion of 50 g glucose, respectively. The mean insulin area response following ingestion of the 50-g glucose meals was 965 ± 162 pmol · h/L. The insulin area responses observed with 25 g galactose, 25 g glucose, 25 g glucose + 25 g galactose, and 50 g lactose were 24%, 51%, 81%, and 85% of that observed with the 50-g glucose meals, respectively. The C-peptide data confirmed the insulin data. The glucagon concentration was unchanged after galactose ingestion and decreased after glucose ingestion. However, the decrease in the glucagon area response observed with 25 g galactose + 25 g glucose or 50 g lactose was less than that with ingestion of 25 g glucose alone. The latter suggests inhibition of the glucagon response to glucose by the added galactose. In conclusion, ingested galactose results in only a modest increase in plasma glucose concentration. The glucose area responses to galactose and glucose are additive. Oral galactose is a relatively potent insulin secretagogue, and the insulin response is also additive to that following glucose ingestion. Ingestion of glucose with galactose markedly reduces the increase in plasma galactose concentration. The mechanism of this effect remains to be defined.

Dose-dependency of the glycemic response to starch-rich meals in insulin-dependent diabetic subjects: Studies at constant insulinemia

The study objective was to determine the dose-response relationship of postprandial blood glucose response areas to the amount of starch ingested in insulin-dependent diabetic (IDDM) subjects. Three test meals were served in random order with a 7-day interval to seven IDDM subjects attending the outpatient clinic at Aarhus Kommunehospital. Mixed meals of 23, 46, and 69 g parboiled white rice (raw weight) containing approximately 20, 40, and 60 g available carbohydrate were served cooked on three separate days. The patients had achieved normoglycemic blood glucose levels 2 hours before meal intake by means of an artificial pancreas (Biostator, Miles Laboratories, Elkhart, IN), which also provided constant insulin infusion during the study periods (0 to 180 minutes). A clear-cut dose-response relationship between the amount of starch ingested and postprandial peak blood glucose values ( r = .96) as well as glucose response areas ( r = .99) was found. Glucose response areas to meals containing 20, 40, and 60 g carbohydrate differed significantly ( P < .01), attaining 291 ± 77, 643 ± 75, and 878 ± 99 mmol/L × 180 minutes, respectively. Glucosuria accounted for 0.6 and 1.6 g (NS) after 20 and 40 g carbohydrate, whereas 5.0 glucose ( P < .05) was detected following 60 g carbohydrate. Similar mean serum free insulin levels (range, 102 to 150 pmol/L) during the three study periods were found.

Effect of added fat on plasma glucose and insulin response to ingested potato in individuals with NIDDM.

In normal subjects, ingestion of butter with potato resulted in considerably lower blood glucose levels but similar or higher insulin concentrations compared with those observed in the same subjects after potato ingestion alone. We determined whether butter ingested with potato would result in a greater stimulation in insulin secretion than ingestion of potato alone in subjects with NIDDM. Seven male subjects with untreated NIDDM ingested 50 g CHO alone or 50 g CHO with 5, 15, 30, or 50 g fat as a breakfast meal. Fat was ingested in the form of butter, and CHO was given in the form of potato. Subjects received 50 g glucose on two separate occasions for comparative purposes. The subjects also were given only water and were studied over the same time period (water control). Plasma glucose, glucagon, alpha-amino nitrogen, nonesterified fatty acids, serum insulin, C-peptide, and triglyceride concentrations were determined over 5 h. The integrated area responses were quantified over the 5-h period using the water control as a baseline. The mean plasma glucose area response after ingestion of potato with or without the various amounts of butter were all similar and were 82% of that observed after ingestion of 50 g glucose. The mean insulin area response to potato alone was 532 pmol.h.L-1. The mean insulin area responses to potato plus 5,15,30, and 50 g of fat meals were 660,774,750, and 756 pmol.h.L-1, respectively. Thus, the mean insulin areas were all greater than for ingestion of potato alone, and a maximal response was observed with addition of 15 g fat (1.4-fold). The C-peptide data did not confirm an increase in insulin secretion. Overall the area responses after ingestion of meals containing fat were not different from the response to potato ingestion alone, although the responses were erratic. The glucagon area response was positive after ingestion of all fat containing meals except for that containing only 5 g fat, and there was a dose-response relationship. The plasma alpha-amino nitrogen and nonesterified fatty acid area responses were negative after potato ingestion and were not significantly different when fat was added. The serum triglyceride concentration increase was greater after the ingestion of butter with the potato as expected. In contrast to the results in normal subjects after ingestion of butter with potato, the glucose response was not smaller in subjects with NIDDM. The insulin response was greater. The insulin area response data indicated the presence of a dose-response relationship. Whether similar responses will be observed with other dietary fat and CHO sources remains to be determined.

Dose-dependency of the glycemic response to starch-rich meals in non-insulin-dependent diabetic subjects: Studies with varying amounts of white rice

The study objective was to determine the dose-response relationships between postprandial blood glucose, insulin, and glucagon responses and the amount of starch ingested in non-insulin-dependent diabetic (NIDDM) subjects. Three test meals were served in random order with a 7-day interval. Mixed meals of 23, 46, and 69 g (raw weight) parboiled white rice containing approximately 20, 40, and 60 g available carbohydrate were served cooked with 167 g meat sauce on 3 separate days. Patients ingested the meals after a 12-hour fast. Clear-cut dose-response relationships between the amount of starch ingested and postprandial peak blood glucose values ( R = .99), glucose response areas ( R = .99), and insulin response areas ( R = .98) were found. Glucose response areas to meals of 20, 40, and 60 g carbohydrate as white rice differed significantly ( P < .05) at 139 ± 58, 285 ± 86, and 453 ± 113 mmol/L × 280 min, respectively. Insulin response areas to meals of 23 g rice (11.382 ± 2,220 pmol/L × 240 min) were significantly lower compared with response areas to 46 g rice (18.138 ± 3,522 pmol/L × 240 min) and 69 g rice (21.312 ± 2,970 pmol/L × 240 min), with the latter two values being similar. Glucagon response areas showed an inverse pattern to glucose response areas, reaching 3,450 ± 823, 2,715 ± 651, and 2,168 ± 553 pmol/L × 240 min, but differences did not reach statistical significance.

The effect of fat and carbohydrate on plasma glucose, insulin, C-peptide, and triglycerides in normal male subjects.

Ten normal subjects were given 50 g starch, or 50 g starch + 50 g fat as a breakfast meal. The starch was given in the form of potato; the fat was given in the form of butter. The meals were ingested at 8 a.m. Plasma glucose, insulin, C-peptide, and triglyceride concentrations were measured at various time points for 4 hours after each meal. The net 4-hour postprandial area responses to the ingested meals were determined using the trapezoid rule, with the fasting glucose concentration, measured at the same time points for 4 hours as a baseline. The glucose area response was 2.2 mmol hour/l following the potato meal. This was significantly reduced following ingestion of the meal containing fat (1.3 mmol hour/l) (p < 0.01). The insulin area response was slightly greater following the meal containing fat (459 pmol hour/l) compared to potato alone (423 pmol hour/l) (p < 0.01). The C-peptide area response following the meal containing fat was 0.80 pmol hour/ml, clearly greater than following potato alone (0.58 pmol hour/ml) (p < 0.01). The triglyceride area response also was much greater following the meal containing fat compared to potato alone (0.74 and 0.08 mmol hour/l, respectively). The mechanism of the attenuated glucose response to carbohydrate ingestion with a fat-containing meal is unknown. It may be due to the release of an enteric hormone that increases glucose disposal, either directly or indirectly, through insulin.