Metabolic response to cottage cheese or egg white protein, with or without glucose, in type II diabetic subjects.

Test meals with 25 g protein in the form of cottage cheese or egg white were given with or without 50 g glucose to male subjects with mild to moderately severe, untreated, type II diabetes. Water was given as a control meal. The glucose, insulin, C-peptide, alpha amino nitrogen (AAN), glucagon, plasma urea nitrogen (PUN), nonesterified fatty acid (NEFA), and triglyceride area responses were determined using the water meal as a baseline. The glucose area responses following ingestion of cottage cheese or egg white were very small compared with those of the glucose meal, and were not significantly different from one another. The serum insulin area response was 3.6-fold greater following ingestion of cottage cheese compared with egg white (309 v 86 pmol/L.h). The simultaneous ingestion of glucose with cottage cheese or egg white protein decreased the glucose area response to glucose by 11% and 20%, respectively. When either protein was ingested with glucose, the insulin area response was greater than the sum of the individual responses, indicating a synergistic effect (glucose alone, 732 pmol/L.h; glucose with cottage cheese, 1,637 pmol/L.h; glucose with egg white, 1,213 pmol/L.h). The C-peptide area response was similar to the insulin area response. The AAN area response was approximately twofold greater following ingestion of cottage cheese compared with egg white. Following ingestion of glucose, it was negative. When protein was ingested with glucose, the AAN area responses were additive. The glucagon area response was similar following ingestion of cottage cheese or egg white protein. Following glucose ingestion, the glucagon area response was negative.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Carbohydrate metabolism in pregnancy. XIV. Relationships between circulating glucagon,insulin, glucose and amino acids in response to a “mixed meal” in late pregnancy

Gestational influences upon the changes in circulating glucose, amino acids, insulin, and glucagon after the ingestion of a “mixed meal” containing carbohydrate (50 g), protein (25 g), and fat (10 g) were examined. Nine subjects were tested during weeks 30–40 of gestation and again 6–8 wk postpartum. The “mixed meal” elicited greater and more prolonged increases in plasma glucose antepartum, whereas the increments in total serum amino acids were blunted at all time points. In the face of greater glycemic but lesser aminogenic stimulation, the integrated increase in plasma insulin was 60% greater antepartum than post partum, whereas the increment in glucagon was not significantly altered. Thus, integrated insulin/glucagon response was increased during antepartum studies. The insulin preponderance following alimentary challenge with mixed nutrients would suggest that the anabolism of ingested amino acids is “facilitated” during late human pregnancy.     

Food restriction retards age-related histological changes in rat small intestine

Previous studies have reported that small and large intestinal crypt hyperplasia and hyperproliferation occur in senescent rats about 27 mo of age. We have studied duodenal and ileal architecture in ad libitum chow-fed rats and have demonstrated that the increase in duodenal crypt depth and crypt hyperplasia do not develop throughout the life span, but become apparent at 21 and 27 mo of age. These crypt hyperplastic features occur without a change in duodenal villus cell number. Ileal villus cellularity increased throughout the life span, suggesting exposure to a gradually increasing luminal nutrient load. Diet restriction to 60% of the ad libitum feeding rate prolonged the life span of animals from 27 to greater than 33 mo and prevented both the duodenal hyperplasia and the increase in ileal villus cell numbers to the age of 27 mo. Thirty-three-month diet-restricted rats did show evidence of duodenal crypt hyperplasia. We conclude that proximal intestinal hyperplasia is a phenomenon that develops in advanced age, but that ileal villus cellularity increases throughout the ad libitum-fed rodent life span. Diet restriction dramatically retards these intestinal changes that are seen with ad libitum feeding and provides an experimental model for the study of age-related cellular changes of the rodent gastrointestinal tract.     

Duodenal infusion of different nutrients and the site of gaseous stimulation influence intestinal gas dynamics

OBJECTIVE: Excessive intestinal gas can be involved in postprandial abdominal symptom generation, but whether the small bowel influences intestinal gas dynamics, depending on the ingested meal, remains to be demonstrated. We compare the intestinal response to a proximal and distal small intestinal gas challenge during different duodenal nutrient components. MATERIAL AND METHODS: We randomly studied 32 healthy subjects, twice, on different days with a gas mixture infused at 12 ml/min either directly into the proximal jejunum or into the ileum; during duodenal lipids, amino acids, glucose, at 1 kcal/min each, or saline (n=8 for each group). Gas evacuation was monitored continuously and abdominal perception and girth changes were assessed. RESULTS: In response to the jejunal gas challenge, duodenal lipids delayed intestinal gas clearance more potently than amino acids (733+/-26 ml and 541+/-108 ml final gas retention; p<0.001), but when gas was directly infused into the ileum the retained volumes were much smaller (271+/-78 ml and 96+/-51 ml; p<0.001). During duodenal glucose, intestinal gas clearance following jejunal or ileal gas infusion was not significantly influenced. Abdominal perception in response to the jejunal and ileal gas challenge only increased slightly during duodenal lipids (2.0+/-0.3 score and 2.3+/-0.6 score; p<0.05 versus control). CONCLUSION: Postprandial intestinal gas clearance is hampered by duodenal lipids and amino acids but not by glucose. Specific inhibitory effects are more pronounced when gas is infused into the jejunum, which underlines the importance of the small intestine in postprandial gas retention.     

Effects of intraluminal peptide YY on pancreatic function.

Peptide YY (PYY) is released postprandially into both the circulation and the distal intestinal lumen. While circulating PYY inhibits pancreatic secretion and insulin release, the effects of intraluminal PYY on pancreatic function are unknown. The aim of the present study was to evaluate the effect of exogenous, intraileal luminal PYY on pancreatic exocrine function and fasting glucose levels. Chronic pancreatic and ileal fistulae (50 cm from the ileocecal valve) were created in nine mongrel dogs. The animals were given intravenous infusions of secretin (125 ng/kg/h) and cholecystokinin octapeptide (CCK-8, 50 ng/kg/h) for four hours. At the beginning of the second hour, either normal saline or PYY, at low [physiologic (2 ng/min)] or high [supraphysiologic (50 ng/min)] levels, was infused antegrade into the ileal fistula for two hours. Pancreatic juice was collected for PYY and glucose levels. Ileal luminal PYY infusions had no effect on pancreatic bicarbonate or protein output. Fasting serum PYY and glucose concentrations were unaffected by either dose of intraluminal PYY. We conclude that ileal luminal PYY does not influence pancreatic exocrine function or fasting glucose levels.     

Glucagon secretion in rats bearing a growth hormone producing tumor (MtT-W-15).

The release of glucagon from pancreatic and extrapancreatic sources was studied in normal rats and in rats carrying transplants of a MtT-W-15 tumor which secretes large quantities of growth hormone and prolactin. The tumor-bearing rats had high serum levels of A cell immunoreactive glucagon (IRGa), total immunoreactive glucagon (IRGT) and immunoreactive insulin (IRI) and an increased total glucagon and insulin content of the pancreas. Pancreatic islets isolated from tumor-bearing rats secreted more glucagon under basal conditions but did not respond significantly to low glucose stimulation. However, they contained more insulin per islet and secreted more insulin under basal and stimulated conditions. The serum IRGa response to arginine infusion in vivo was lower in the tumor-bearing than in the normal rats. The introduction of a 5% glucose solution into the small intestine caused similar increases in the level of serum IRGT in the two groups of rats. Thus, the tumor increased the total pancreatic glucagon content and basal secretion, blunted the A cell response to stimulation, but did not significantly alter the secretion of glucagon by the intestine. We attribute these responses to tumor-induced hypersomatotropinism although we cannot rule out an effect of the large amounts of circulating prolactin.     

Therapy of type 2 diabetes mellitus based on the actions of glucagon-like peptide-1

GLP-1 is a peptide hormone from the intestinal mucosa. It is secreted in response to meal ingestion and normally functions in the so-called ileal brake, that is, inhibition of upper gastrointestinal motility and secretion when nutrients are present in the distal small intestine. It also induces satiety and promotes tissue deposition of ingested glucose by stimulating insulin secretion. Thus, it is an essential incretin hormone. In addition, the hormone has been demonstrated to promote insulin biosynthesis and insulin gene expression and to have trophic effects on the beta cells. The trophic effects include proliferation of existing beta cells, maturation of new cells from duct progenitor cells and inhibition of apoptosis. Furthermore, glucagon secretion is inhibited. Because of these effects, the hormone effectively improves metabolism in patients with type 2 diabetes mellitus. Thus, continuous subcutaneous administration of the peptide for six weeks in patients with rather advanced disease greatly improved glucose profiles and lowered body weight, haemoglobin A(1C), and free fatty acids (FFA). In addition, insulin sensitivity doubled and insulin responses to glucose were greatly improved. There were no side effects. Continuous administration is necessary because of rapid degradation by the enzyme dipeptidyl peptidase-IV. Alternative approaches include the use of analogues that are resistant to the actions of the enzyme, as well as inhibitors of the enzyme. Both approaches have shown remarkable efficacy in both experimental and clinical studies. The GLP-1-based therapy of type 2 diabetes, therefore, represents a new and attractive alternative.     

Circulating somatostatin after oral glucose in hypothyroidism

The response of circulating somatostatin-like immunoactivity (SLI) to oral glucose and its relation to other pancreatic islet cell hormones were studied in 10 hypothyroid subjects before and after treatment. None of the patients suffered from diabetes mellitus or obesity. Compared with normal controls, the hypothyroid subjects had higher fasting and stimulated SLI levels but lower fasting pancreatic glucagon levels. Integrated glucose and insulin responses following glucose ingestion were normal, but the peak insulin response was delayed to 120 min suggesting impaired pancreatic beta-cell response to oral glucose. On the other hand, the peak response of plasma C-peptide was higher probably because of a reduction in metabolic clearance. In both hypothyroid subjects and controls, a significant correlation was found between the maximal increment of SLI and the maximal decrement of glucagon following oral glucose. In conclusion, plasma SLI is increased in hypothyroidism. The changes in SLI may be due to either an increased hormonal secretion or a reduced metabolic clearance in hypothyroidism. This elevated SLI might contribute to the slower gastrointestinal motility observed in hypothyroidism. Our data also suggest that the reduction in glucagon secretion may be secondary to the increase in circulating SLI.     

Antidiabetogenic action of cholecystokinin-8 in type 2 diabetes

Cholecystokinin (CCK) is a gut hormone and a neuropeptide that has the capacity to stimulate insulin secretion. As insulin secretion is impaired in type 2 diabetes, we explored whether exogenous administration of this peptide exerts antidiabetogenic action. The C-terminal octapeptide of CCK (CCK-8) was therefore infused i.v. (24 pmol/kg x h) for 90 min in six healthy postmenopausal women and in six postmenopausal women with type 2 diabetes. At 15 min after start of infusion, a meal was served and ingested during 10 min. On a separate day, saline was infused instead of CCK-8. In both healthy subjects and subjects with type 2 diabetes, CCK-8 reduced the increase in circulating glucose after meal ingestion and potentiated the increase in circulating insulin. The ratio between the area under the curves for serum insulin and plasma glucose during the 15- to 75-min period after meal ingestion was increased by CCK-8 by 198 +/- 18% in healthy subjects (P = 0.002) and by 474 +/- 151% (P = 0.038) in subjects with type 2 diabetes. In contrast, the increase in the circulating levels of gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), or glucagon after meal ingestion was not significantly affected by CCK-8. The study therefore shows that CCK-8 exerts an antidiabetogenic action in both healthy subjects and type 2 diabetes through an insulinotropic action that most likely is exerted trough a direct islet effect. As at the same time, CCK-8 was infused without any adverse effects, the study suggests that CCK is a potential treatment for type 2 diabetes.     

Effects of ethanol ingestion on glucose tolerance and insulin secretion in normal and diabetic subjects

To investigate the effect of ethanol on carbohydrate homeostasis in circumstances in which food and ethanol are usually ingested, ethanol was administered hourly in the afternoon prior to the ingestion of a glucose load at 5:00 p.m. in a group of normal subjects and in mild diabetics. In both groups the blood glucose levels following the glucose load were $\text{30–80 mg}\text{100 ml}$ lower and the early insulin secretory response (15–45 min) was 35%–40% higher after ethanol ingestion. In contrast, ethanol intake had no effect on the glucagon response to glucose ingestion. These data suggest that ethanol enhances glucose-stimulated insulin secretion. The dampened blood glucose rise observed with ethanol may be related to the augmented insulin response or to decreased gastrointestinal absorption of glucose. In mild diabetic patients, moderate intake of ethanol is without acute deleterious effects on carbohydrate homeostasis and may in some instances improve the blood glucose response to ingested carbohydrate.     

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 α-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 α-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.     

Glucagon secretion in rats with non-insulin-dependent diabetes: an in vivo and in vitro study

Non-insulin-dependent diabetes ( NIDD ) was obtained in adult rats following a neonatal streptozotocin injection. Rats with NIDD exhibited a chronic low-insulin response to glucose in vivo, slightly elevated basal plasma glucose values (less than 2 g/l) and low pancreatic insulin stores (50% of the controls). Glucagon secretion was studied in this model, in vivo and in vitro using the isolated perfused pancreas technique. Normal basal plasma glucagon levels were observed in the fed state and were in accordance with normal basal glucagon release in vitro. The pancreatic glucagon stores were normal in the diabetics. In experiments with the perfused pancreas, the increased glucose concentration suppressed glucagon release as readily in the diabetics as in the controls. Moreover 5.5 mM glucose suppressed glucagon release stimulated by 19 mM arginine to the same extent in both groups. These data indicate that the suppression of A cell function by glucose is normal in rats with NIDD . Theophylline and isoproterenol also produced normal glucagon release in diabetics. By contrast, the glucagon secretion in response to arginine was lower in the diabetics. This was observed either in vivo (arginine infusion) or in vitro in the presence or the absence of glucose in the perfusate. But in the presence of theophylline the response to arginine was normalized in the diabetics. Impairment of A cell function of the diabetics is not limited to recognition of amino-acids, since acetylcholine evoked a lower glucagon response in the diabetics than in the controls. These defects are different from those described in their B cells.     

Leptin-A regulator of islet function?: Its plasma levels correlate with glucagon and insulin secretion in healthy women

It has previously been demonstrated that plasma leptin correlates to body fat content. It has also been demonstrated that in subjects with normal glucose tolerance, circulating leptin correlates to circulating insulin and to insulin secretion and that these relations are independent of body fat. However, whether leptin also covaries with other islet hormones is not known. We therefore studied the relation between plasma levels of leptin and glucagon secretion and circulating pancreatic polypeptide (PP) in healthy humans. Arginine was injected intravenously (5 g) at fasting and at 14 and 28 mmol/L glucose in 71 postmenopausal women with normal glucose tolerance. In a multivariate analysis controlling for the influence of the body mass index, we found that circulating leptin correlated significantly to fasting insulin (r = .38, P = .002), and to circulating insulin at 14 mmol/L glucose (r = .29, P = .0019) and 28 mmol/L glucose (r = .32, P = .009), as well as to the insulin response to arginine at all three glucose levels (r> .30, P < .013). Circulating leptin, independently of the body mass index, also correlated to fasting glucagon (r = .31, P = .012) and to the glucagon response to arginine at all three glucose levels (r> .28, P < .038). In contrast, circulating leptin did not correlate to plasma glucagon at 14 or 28 mmol/L glucose or to plasma levels of PP. We conclude that circulating leptin correlates to the secretory capacity of both glucagon and insulin but not to the reduction of plasma glucagon during hyperglycemia or to PP in a large group of postmenopausal women. This suggests that islet function is related to circulating leptin in humans.     

Induction of intestinal glucose carriers in streptozocin-treated chronically diabetic rats

The maximal transport capacity (Vmax) for intestinal glucose absorption is increased in experimentally induced chronic diabetes mellitus. Using [3H]phlorizin radioautography, we examined the relation between this increase in transport Vmax and the number and distribution of sodium-glucose co-transporters on the luminal surface of rat ileum. Male Lewis rats were made diabetic with streptozocin. Ninety days later we measured 3-O-methyl-D-glucopyranose absorption and specific [3H]phlorizin binding to the ileal mucosa of the same rats. Net 3-O-methyl-D-glucopyranose flux was 6.9-fold greater in diabetic rats compared with age-matched controls. Specific binding of [3H]phlorizin to the luminal surface was 7.2-fold greater in the diabetic rats. Radioautography revealed that, in chronic diabetes, specific phlorizin binding extends into the midvillus region of the ileum, whereas in age-matched controls, it is confined to villus tips. We believe that, in untreated diabetes, a larger fraction of intestinal villus epithelial cells participate in glucose absorption.     

The metabolic response to various doses of fructose in type II diabetic subjects.

Eight men with untreated type II diabetes were given 480 mL water containing 15 g, 25 g, 35 g, and 50 g fructose orally, in random sequence. The same subjects were given the same volume of water as a control. They also were given 50 g glucose on two occasions for comparative purposes. Plasma glucose, urea nitrogen, and glucagon, and serum insulin, C-peptide, alpha-amino-nitrogen (AAN), nonesterified fatty acids (NEFA), and triglycerides were determined over the subsequent 5-hour period. The area responses to each dose of fructose were calculated and compared with the water control. The integrated glucose area dose-response was curvilinear, with little increase in glucose until 50 g fructose was ingested. With the 50-g dose, the area response was 25% of the response to 50 g glucose. The insulin response also was curvilinear, but the curve was opposite to that of the glucose curve. Even the smallest dose of fructose resulted in a relatively large increase in insulin, and a near-maximal response occurred with 35 g. The area response to 50 g fructose was 39% of that to 50 g glucose. The C-peptide data were similar to the insulin data. The AAN area response to fructose ingestion was negative. However, the response was progressively less negative with increasing doses. The glucagon area response was positive, but a dose-response relationship was not apparent. The glucagon area response was negative after glucose ingestion, as expected. The urea nitrogen area response was negative, but again, a dose-response relationship to fructose ingestion was not present.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biologic actions and therapeutic potential of the proglucagon-derived peptides

The actions of the structurally related proglucagon-derived peptides (PGDPs)-glucagon, glucagon-like peptide (GLP)-1 and GLP-2-are focused on complementary aspects of energy homeostasis. Glucagon opposes insulin action, regulates hepatic glucose production, and is a primary hormonal defense against hypoglycemia. Conversely, attenuation of glucagon action markedly improves experimental diabetes, hence glucagon antagonists may prove useful for the treatment of type 2 diabetes. GLP-1 controls blood glucose through regulation of glucose-dependent insulin secretion, inhibition of glucagon secretion and gastric emptying, and reduction of food intake. GLP-1-receptor activation also augments insulin biosynthesis, restores beta-cell sensitivity to glucose, increases beta-cell proliferation, and reduces apoptosis, leading to expansion of the beta-cell mass. Administration of GLP-1 is highly effective in reducing blood glucose in subjects with type 2 diabetes but native GLP-1 is rapidly degraded by dipeptidyl peptidase IV. A GLP-1-receptor agonist, exendin 4, has recently been approved for the treatment of type 2 diabetes in the US. Dipeptidyl-peptidase-IV inhibitors, currently in phase III clinical trials, stabilize the postprandial levels of GLP-1 and gastric inhibitory polypeptide and lower blood glucose in diabetic patients via inhibition of glucagon secretion and enhancement of glucose-stimulated insulin secretion. GLP-2 acts proximally to control energy intake by enhancing nutrient absorption and attenuating mucosal injury and is currently in phase III clinical trials for the treatment of short bowel syndrome. Thus the modulation of proglucagon-derived peptides has therapeutic potential for the treatment of diabetes and intestinal disease.     

Elevated plasma levels of glucagon-like peptide-1 after oral glucose ingestion in patients with pancreatic diabetes

OBJECTIVE: The purpose of the present study was to evaluate plasma glucagon-like peptide-1 (GLP-1) responses after oral glucose ingestion in patients with chronic pancreatitis and to clarify how GLP-1 secretion relates to pancreatic diabetes. METHODS: An oral glucose tolerance test (OGTT) was performed in 17 patients with chronic pancreatitis. Plasma glucose, immunoreactive insulin (IRI), C-peptide, glucagon, and GLP-1 levels at each time point during OGTT were measured. The diagnosis of chronic pancreatitis was made by the findings of endoscopic retrograde pancreatography (ERP): evident dilation of the main pancreatic duct with or without pancreatolithiasis. RESULTS: The patients were divided into three groups according to the World Health Organization classification of diabetes based on plasma glucose levels after OGTT. The groups were: normal (three patients), impaired glucose tolerant (IGT) (six patients), and diabetic (DM) (eight patients). In the DM group, IRI and C-peptide response levels after oral glucose ingestion were significantly reduced as compared with those of the normal and IGT groups. No significant glucagon responses to oral glucose ingestion were found in the three groups. In contrast, plasma GLP-1 levels were significantly elevated after oral glucose ingestion in the DM groups as compared with normal and IGT groups. CONCLUSIONS: The present study affords evidence that plasma GLP-1 levels become elevated with development of pancreatic diabetes, although the precise mechanism of this elevation remains undetermined.     

Impact of glucagon response on early postprandial glucose excursions irrespective of residual β‐cell function in type 1 diabetes: A cross‐sectional study using a mixed meal tolerance test

Aims/IntroductionControlling postprandial glucose levels in patients with type 1 diabetes is challenging even under the adequate treatment of insulin injection. Recent studies showed that dysregulated glucagon secretion exacerbates hyperglycemia in type 2 diabetes patients, but little is known in type 1 diabetes patients. We investigated whether the glucagon response to a meal ingestion could influence the postprandial glucose excursion in patients with type 1 diabetes.Materials and MethodsWe enrolled 34 patients with type 1 diabetes and 23 patients with type 2 diabetes as controls. All patients underwent a liquid mixed meal tolerance test. We measured levels of plasma glucose, C‐peptide and glucagon at fasting (0 min), and 30, 60 and 120 min after meal ingestion. All type 1 diabetes patients received their usual basal insulin and two‐thirds of the necessary dose of the premeal bolus insulin.ResultsThe levels of plasma glucagon were elevated and peaked 30 min after the mixed meal ingestion in both type 1 diabetes and type 2 diabetes patients. The glucagon increments from fasting to each time point (30, 60 and 120 min) in type 1 diabetes patients were comparable to those in type 2 diabetes patients. Among the type 1 diabetes patients, the glucagon response showed no differences between the subgroups based on diabetes duration (<5 vs ≥5 years) and fasting C‐peptide levels (<0.10 vs ≥0.10 nmol/L). The changes in plasma glucose from fasting to 30 min were positively correlated with those in glucagon, but not C‐peptide, irrespective of diabetes duration and fasting C‐peptide levels in patients with type 1 diabetes.ConclusionsThe dysregulated glucagon likely contributes to postprandial hyperglycemia independent of the residual β‐cell functions during the progression of type 1 diabetes.