Glucose Homeostasis In Subjects Research Articles

The effect of statin treatment on glucose homeostasis in prediabetic individuals: A prospective, randomized, controlled trial.

This study aimed to evaluate the effects of rosuvastatin and pravastatin on glucose homeostasis and other biomarkers in individuals at high risk of developing diabetes. This prospective, randomized, open-labeled, and controlled trial included prediabetic individuals with impaired fasting glucose and impaired glucose tolerance. The participants were randomized into three groups: rosuvastatin (10 mg), pravastatin (40 mg), or control. Biomarkers of diabetes and glucose and insulin responses to oral glucose tolerance tests were assessed at baseline and after 6 months of treatment. The primary outcomes were comparisons of glucose homeostasis and biomarkers of diabetes among groups at baseline and after 6 months of treatment. A total of 141 subjects with impaired fasting glucose (IFG) were screened and 41 participants were recruited. Twenty-two subjects were randomized to either the rosuvastatin or pravastatin group and 19 subjects were assigned to the control group. After 6 months of treatment, all groups had similar cholesterol and triglyceride levels. Likewise, HbA1c levels, glucose, and insulin excursions during oral glucose tolerance test, were similar among the three groups. However, compared to the other groups, the rosuvastatin group had higher homeostasis model assessment for insulin resistance (HOMA-IR) (insulin resistance) and a lower Matsuda index (insulin sensitivity). Among prediabetic individuals with IFG, rosuvastatin treatment was associated with increased insulin resistance and decreased insulin sensitivity compared to pravastatin and control groups. Further research is needed to elucidate the underlying mechanisms and clinical implications of these findings.

Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

ObjectiveElevated serum ferritin has been linked to type 2 diabetes (T2D) and adverse health outcomes in subjects with the Metabolic Syndrome (MetS). As the mechanisms underlying the negative impact of excess iron have so far remained elusive, we aimed to identify potential links between iron homeostasis and metabolic pathways. MethodsIn a cross-sectional study, data were obtained from 163 patients, allocated to one of three groups: (1) lean, healthy controls (n = 53), (2) MetS without hyperferritinemia (n = 54) and (3) MetS with hyperferritinemia (n = 56). An additional phlebotomy study included 29 patients with biopsy-proven iron overload before and after iron removal. A detailed clinical and biochemical characterization was obtained and metabolomic profiling was performed via a targeted metabolomics approach. ResultsSubjects with MetS and elevated ferritin had higher fasting glucose (p < 0.001), HbA1c (p = 0.035) and 1 h glucose in oral glucose tolerance test (p = 0.002) compared to MetS subjects without iron overload, whereas other clinical and biochemical features of the MetS were not different. The metabolomic study revealed significant differences between MetS with high and low ferritin in the serum concentrations of sarcosine, citrulline and particularly long-chain phosphatidylcholines. Methionine, glutamate, and long-chain phosphatidylcholines were significantly different before and after phlebotomy (p < 0.05 for all metabolites). ConclusionsOur data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism.

Randomized, double-blind, placebo-controlled trial to evaluate the effect of Helicobacter pylori eradication on glucose homeostasis in type 2 diabetic patients

Background and aimsLiterature data suggest an association between Helicobacter pylori infection and glucose homeostasis. However, a causative link between them has not been demonstrated yet. The aim of this study is to investigate the effect of H. pylori eradication on glucose homeostasis in patients with type 2 diabetes. Methods and resultsA randomized, double-blind, placebo-controlled trial was conducted to investigate the effect of H. pylori eradication on glucose homeostasis in 154 patients with type 2 diabetes and who tested positive for H. pylori infection (mean age (SD), 63.1 (8.1) years). Subjects were assigned to H. pylori eradication treatment or placebo. Metabolic and inflammatory parameters were measured in all subjects at baseline and 4 weeks after the treatment. H. pylori eradication led to an improvement in glucose homeostasis, measured by HOMA-IR (p < 0.001) and KITT (0 = 0.041), due to the decrease in fasting insulin levels (p = 0.004). The results also showed that lower levels of inflammatory parameters were present after eradication. ConclusionTo our knowledge this is the first randomized, double blind, controlled study where the effect of H. pylori eradication on glucose homeostasis in subjects with type 2 diabetes has been investigated. Our findings demonstrate that H. pylori eradication improves glucose homeostasis in patients with type 2 diabetes through a decrease in pro-inflammatory factors. Trial registration number: ACTRN12609000255280 (https://www.anzctr.org.au/).

No Effect of High-Dose Vitamin D Treatment on β-Cell Function, Insulin Sensitivity, or Glucose Homeostasis in Subjects With Abnormal Glucose Tolerance: A Randomized Clinical Trial.

There has been conflicting evidence regarding the potential role of vitamin D in glucose homeostasis. This study was designed to investigate the effect of high-dose vitamin D3 treatment on β-cell function, insulin sensitivity, and glucose tolerance in subjects with prediabetes or diet-treated type 2 diabetes. Subjects (n = 44) were randomized to 30,000 IU vitamin D3 once weekly or placebo for 8 weeks. Hyperglycemic clamp assessed first-phase (0-12 min) and second-phase (12-120 min) insulin response, insulin sensitivity, and disposition index (DI). An oral glucose tolerance test assessed glucose tolerance and glycosylated hemoglobin assessed glycemic control. A total of 21 (vitamin D) and 22 (placebo) subjects completed the study, respectively. Season-adjusted 25-OH-vitamin D [25(OH)D] levels were doubled in the active treated group (43-82 nmol/L). No effect of vitamin D treatment, compared with placebo, was seen on first-phase or second-phase insulin secretion. There were no group differences in insulin sensitivity, DI, or any measures of glycemic control. No hypercalcemia or other adverse effects of vitamin D treatment were seen compared with placebo. Subgroup analyses of those with the lowest basal and greatest increase in 25(OH)D levels did not change these results. This study gives no support for any substantial effect of high-dose vitamin D treatment for 8 weeks in prediabetes or diet-treated type 2 diabetes on β-cell function, insulin sensitivity, or glycemic control.

A Randomised Crossover Trial: The Effect of Inulin on Glucose Homeostasis in Subtypes of Prediabetes

Background: Fermentable carbohydrates (FCHO) have been shown to improve insulin sensitivity in normoglycaemic and insulin-resistant subjects. However, there are no data on subjects with prediabetes. We aimed to investigate the effect of the FCHO inulin, on glucose homeostasis in subjects with prediabetes. Methods: In a double-blind and placebo-controlled crossover study, 40 volunteers with prediabetes were randomly allocated to take 30 g/day of inulin or cellulose for 2 weeks in a crossover trial, following a 4-week dose-escalation run-in. Fasting insulin and glucose were measured for all subjects. Fifteen of the 40 subjects also underwent a meal tolerance test to assess insulin sensitivity, free fatty acids and glucagon-like peptide-1 concentrations. A subanalysis was carried out to examine any differences between the prediabetes subtypes. Results: Inulin was associated with a significant increase in _{(0-30 min)}incremental AUC (iAUC) for insulin (treatment: p < 0.04) and _{(0-60 min)}iAUC for insulin (treatment: p < 0.04) compared to control. There was a significant reduction in insulin resistance measured by the homeostatic model assessment in the isolated-impaired fasting glucose (p < 0.05) but not in the isolated-impaired glucose tolerance groups (p = 0.59). Conclusion: The FCHO, inulin, may have unique metabolic effects that are of particular benefit to people at risk of diabetes, which warrant further investigation.

Relationship between Serum 1,5-anhydroglucitol, as an Indicator of Postprandial Glycemic Control, and Serum Uric Acid, Considering the Renal Threshold for Glucosuria in the Elderly

Postprandial hyperglycemia is an independent risk factor for cardiovascular disease-related morbidity and mortality, not only in diabetes mellitus (DM) but also in impaired glucose tolerance. Postprandial glycemic levels have been difficult to monitor, but recently 1,5-anhydroglucitol (1,5-AG) levels have proven to be beneficial for this purpose. In humans, 1,5-AG, a 1-deoxy-glucopyranose, is a major and abundant polyol, of which 90% is derived from ingested food, and little is produced from glycogen in the liver. Nearly all 1,5-AG is reabsorbed in normoglycemia, but the reabsorption rate decreases in proportion to the degree of hyperglycemia above the renal threshold for glucosuria, which is 160 to 180 mg dL. Glucosuria appears if the level of blood glucose rises above this level. The renal reabsorption of 1,5-AG is competitively inhibited by glucosuria. The 1,5-AG level appears to be well suited for monitoring glucose homeostasis in subjects with near-normoglycemia or with postprandial hyperglycemia without fasting hyperglycemia. However, few studies have shown a relationship, which remains controversial, between the serum 1,5-AG level and the age or sex of nondiabetic subjects. Therefore, we investigated the effects of sex and age on serum 1,5-AG levels in nondiabetic subjects. This study has demonstrated that the serum 1,5-AG concentration tends to decrease with age and is significantly correlated with age in both males and females. Moreover, the serum 1,5-AG concentration tends to be higher in males than in females, but this sex difference decreases with age. The 1,5-AG level is less sensitive for identifying postprandial hyperglycemia in elderly women with near-normoglycemia, partly because they have a higher renal threshold for glucose. Lifestyle changes in recent years have led to concerns about not only postprandial hyperglycemia, but also hyperuricemia. Serum levels of UA are related to urethritis and to several more serious conditions, such as kidney disease, hypertension, DM, metabolic syndrome, and cardiovascular disease. Furthermore, increased serum UA levels after menopause suggest that estrogen promotes UA excretion in the kidneys. A previous study has shown that estradiol suppresses levels of urate transporter 1 (URAT1), a urate reabsorptive transporter, in the mouse kidney. In the relationship between the levels of uric acid and glucose metabolism, a previous study has found that both serum UA levels and the frequency of hyperuricemia increase with moderately increasing levels of HbA1c (6.0%―6.9%) and then decrease as levels of HbA1c increase further, due to the uricosuric effect of glucosuria.

Effect of Inulin on Glucose Homeostasis in Subjects with Prediabetes

Effect of Inulin on Glucose Homeostasis in Subjects with Prediabetes

GSK256073, a selective agonist of G‐protein coupled receptor 109A (GPR109A) reduces serum glucose in subjects with type 2 diabetes mellitus

This clinical trial assessed whether a potent, selective GPR109A agonist, GSK256073, could, through inhibition of lipolysis, acutely improve glucose homeostasis in subjects with type 2 diabetes mellitus. Thirty-nine diabetic subjects were enrolled in the randomized, single-blind, placebo-controlled, three-period crossover trial. Each subject received placebo and two of four regimens of GSK256073 for 2 days. GSK256073 was dosed 5 mg every 12 h before breakfast and supper (BID), 10 mg every 24 h before breakfast (QD), 25 mg BID and 50 mg QD. The change from baseline weighted mean glucose concentration for an interval from 24 to 48 h after the initial drug dose was significantly reduced for all GSK256073 regimens, reaching a maximum of -0.87 mmol/l (-1.20, -0.52) with the 25 mg BID dose. Sustained suppression of non-esterified fatty acid (NEFA) and glycerol concentrations was observed with all GSK256073 doses throughout the 48-h dosing period. Serum insulin and C-peptide concentrations fell in concert with glucose concentrations and calculated HOMA-IR scores decreased 27-47%, consistent with insulin sensitization. No marked differences were evident between either 10 and 50 mg total daily doses or QD versus BID dosing. Administration of a GPR109A agonist for 2 days significantly decreased serum NEFA and glucose concentrations in diabetic subjects. Glucose improvements were associated with decreased insulin concentrations and measures of enhanced insulin sensitivity. Improved glucose control occurred with GSK256073 doses that were generally safe and not associated with events of flushing or gastrointestinal disturbances.

Effect of acacia polyphenol on glucose homeostasis in subjects with impaired glucose tolerance: A randomized multicenter feeding trial

Numerous in vitro and animal studies, as well as clinical trials have indicated that plant-derived polyphenols exert beneficial effects on glucose intolerance or type 2 diabetes. This clinical study aimed to investigate the effects of acacia polyphenol (AP) on glucose and insulin responses to an oral glucose tolerance test (OGTT) in non-diabetic subjects with impaired glucose tolerance (IGT). A randomized, double-blind, placebo-controlled trial was conducted in a total of 34 enrolled subjects. The subjects were randomly assigned to the AP-containing dietary supplement (AP supplement; in a daily dose of 250 mg as AP; n=17) or placebo (n=17) and the intervention was continued for 8 weeks. Prior to the start of the intervention (baseline) and after 4 and 8 weeks of intervention, plasma glucose and insulin were measured during a two-hour OGTT. Compared with the baseline, plasma glucose and insulin levels at 90 and/or 120 min, as well as the total area under the curve values during the OGTT (AUC0→2h) for glucose and insulin, were significantly reduced in the AP group, but not in the placebo group after intervention for 8 weeks. The decline from baseline in plasma glucose and insulin at 90 or 120 min of the OGTT for the AP group was significantly greater compared with that of the placebo group after 8 weeks of intervention. No AP supplement-related adverse side-effects nor any abnormal changes in routine laboratory tests and anthropometric parameters were observed throughout the study period. The AP supplement may have the potential to improve glucose homeostasis in subjects with IGT.

Assessment of glycemic response to an oral glucokinase activator in a proof of concept study: application of a semi-mechanistic, integrated glucose-insulin-glucagon model

A proof of concept study was conducted to investigate the safety and tolerability of a novel oral glucokinase activator, LY2599506, during multiple dose administration to healthy volunteers and subjects with Type 2 diabetes mellitus (T2DM). To analyze the study data, a previously established semi-mechanistic integrated glucose-insulin model was extended to include characterization of glucagon dynamics. The model captured endogenous glucose and insulin dynamics, including the amplifying effects of glucose on insulin production and of insulin on glucose elimination, as well as the inhibitory influence of glucose and insulin on hepatic glucose production. The hepatic glucose production in the model was increased by glucagon and glucagon production was inhibited by elevated glucose concentrations. The contribution of exogenous factors to glycemic response, such as ingestion of carbohydrates in meals, was also included in the model. The effect of LY2599506 on glucose homeostasis in subjects with T2DM was investigated by linking a one-compartment, pharmacokinetic model to the semi-mechanistic, integrated glucose-insulin-glucagon system. Drug effects were included on pancreatic insulin secretion and hepatic glucose production. The relationships between LY2599506, glucose, insulin, and glucagon concentrations were described quantitatively and consequently, the improved understanding of the drug-response system could be used to support further clinical study planning during drug development, such as dose selection.

The Acute Impact of Ingestion of Sourdough and Whole-Grain Breads on Blood Glucose, Insulin, and Incretins in Overweight and Obese Men

Consumption of whole-grain and sourdough breads is associated with improved glucose homeostasis. We examined the impact of commercial breads on biomarkers of glucose homeostasis in subjects at risk for glucose intolerance. In a randomized, crossover study, overweight or obese males ingested 11-grain, sprouted-grain, 12-grain, sourdough, or white bread on different occasions, matched for available carbohydrate (50 g) in part 1 (n = 12) and bread mass (107 g) in part 2 (n = 11), and blood glucose, insulin and glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were determined for 3 h. In part 1, glucose response for sprouted-grain was lower than 11-grain, sourdough, and white breads. Insulin area under the curve (AUC) for sourdough and white was lower than 11-grain and sprouted-grain breads. GLP-1 response to sourdough was lower than all breads. In part 2, glucose and insulin AUC for sourdough was greater than 11-grain, sprouted-grain, and 12-grain breads. Sprouted-grain bread improved glycemia by lowering glucose response and increasing GLP-1 response. In overweight and obese men, the glycemic response to sprouted grain bread was reduced in both parts 1 and 2 while the other whole-grain test breads did not improve metabolic responses in the acute postprandial state.

Prospective Associations of Vitamin D With β-Cell Function and Glycemia

OBJECTIVETo examine the prospective associations of baseline vitamin D [25-hydroxyvitamin D; 25(OH)D] with insulin resistance (IR), β-cell function, and glucose homeostasis in subjects at risk for type 2 diabetes.RESEARCH DESIGN AND METHODSWe followed 489 subjects, aged 50 ± 10 years, for 3 years. At baseline and follow-up, 75-g oral glucose tolerance tests (OGTTs) were administered. IR was measured using the Matsuda index (ISOGTT) and the homeostasis model assessment of IR (HOMA-IR), β-cell function was determined using both the insulinogenic index divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2), and glycemia was assessed using the area under the glucose curve (AUCglucose). Regression models were adjusted for age, sex, ethnicity, season, and baseline value of the outcome variable, as well as baseline and change in physical activity, vitamin D supplement use, and BMI.RESULTSMultivariate linear regression analyses indicated no significant association of baseline 25(OH)D with follow-up ISOGTT or HOMA-IR. There were, however, significant positive associations of baseline 25(OH)D with follow-up IGI/IR (β = 0.005, P = 0.015) and ISSI-2 (β = 0.002, P = 0.023) and a significant inverse association of baseline 25(OH)D with follow-up AUCglucose (β = −0.001, P = 0.007). Progression to dysglycemia (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) occurred in 116 subjects. Logistic regression analyses indicated a significant reduced risk of progression with higher baseline 25(OH)D (adjusted odds ratio 0.69 [95% CI 0.53–0.89]), but this association was not significant after additional adjustment for baseline and change in BMI (0.78 [0.59–1.02]).CONCLUSIONSHigher baseline 25(OH)D independently predicted better β-cell function and lower AUCglucose at follow-up, supporting a potential role for vitamin D in type 2 diabetes etiology.

Angiotensin type-1 receptor blockade with losartan increases insulin sensitivity and improves glucose homeostasis in subjects with type 2 diabetes and nephropathy

A growing body of evidence supports the concept that treatment with the newer angiotensin type-1 receptor blockers (ARBs) improves glucose homeostasis under conditions wherein it is impaired. Controversy exists, however, regarding the ability of losartan, an older ARB, to exert comparable improvement. The present study was undertaken to evaluate the effects of losartan on glucose homeostasis in subjects with type 2 diabetes and nephropathy. Twenty-seven subjects with type 2 diabetic nephropathy were enrolled in this prospective, randomized, controlled study. Losartan (100 mg daily) or the calcium channel blocker amlodipine (10 mg daily) was administered for a period of 3 months. Fasting blood glucose, serum insulin and C-peptide concentrations were measured at baseline and at the end of the study. Oral glucose tolerance tests were performed to evaluate insulin sensitivity and beta-cell responsiveness. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). Fasting blood glucose, HbA1c, AUC glucose, and urinary protein values were significantly decreased in the losartan group as compared with the amlodipine group (P<0.05). Furthermore, C-peptide concentrations, the insulin sensitivity index, and the insulin-to-glucose ratio were significantly increased after 3 months of therapy with losartan as compared to amlodipine (P<0.05). Reductions of fasting insulin concentrations and HOMA-IR were also observed for the losartan group; however, reductions were not significant when compared with the amlodipine group. In addition to reducing urinary protein excretion, losartan at 100 mg daily increases insulin sensitivity and improves glucose homeostasis in subjects with type 2 diabetic nephropathy.

New Insights into Glucose Regulation

This review article describes the regulation of glucose homeostasis in subjects with and without diabetes based on the emergence of new information and discusses modes of action, attributes, and limitations of current diabetes therapies. In normal physiology, glucose homeostasis is tightly controlled by the interaction of pancreatic and gut hormones. Since the 1920s, diabetes has been viewed as a disease caused by deficient secretion of insulin, resulting in reduced glucose uptake and subsequent hyperglycemia. The discovery in the 1950s of the pancreatic hormone glucagon, which opposes insulin by increasing glucose appearance in the circulation, resulted in a bihormonal model of glucose homeostasis. More recently, with the discovery of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) in the 1970s and the pancreatic hormone amylin in the 1980s, it is now understood that several organs and hormones play roles in maintaining glucose homeostasis. Therapies for diabetes have focused on compensation for deficient insulin action through stimulation of insulin secretion, administration of insulin itself, reduction of peripheral insulin resistance, or decreased glucose absorption from the intestine. The discoveries of amylin and GLP-1 have furthered our understanding of the abnormalities involved in diabetes, enabling the development of additional therapeutic options.

Characterisation of subjects with early abnormalities of glucose tolerance in the Stockholm Diabetes Prevention Programme: the impact of sex and type 2 diabetes heredity

We evaluated the impact of sex and type 2 diabetes heredity on the prevalence and pathogenesis of early abnormalities of glucose homeostasis in subjects participating in the Stockholm Diabetes Prevention Programme. A sample of 3,128 men and 4,821 women, of whom approximately half had a family history of type 2 diabetes (FHD) was categorised according to an OGTT: NGT, IFG, IGT, combined glucose intolerance and type 2 diabetes. The homeostasis model assessment was used to determine insulin sensitivity and beta cell function. Prevalence of early abnormalities of glucose metabolism was two to three times higher in subjects with FHD and two to three times higher in men compared to women. Both maternal and paternal heredity of type 2 diabetes were associated with an increased risk of having early abnormalities of glucose metabolism. However, in women with type 2 diabetes heredity on the father's side seems to have less impact on an increased risk of having type 2 diabetes. Both waist circumference and systolic blood pressure were increased in subjects with abnormalities of glucose homeostasis, whereas insulin sensitivity and beta cell function were decreased. Subjects with IFG had more pronounced impairment of beta cell function and insulin sensitivity than subjects with IGT. An FHD and male sex increased the prevalence of abnormalities of glucose homeostasis. Subjects with IFG had more pronounced defects of insulin secretion and action than subjects with IGT.

Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes

Objective To investigate the effect of 3-months’ daily administration of high doses of sucralose, a non-nutritive sweetener, on glycemic control in subjects with type 2 diabetes. Design A multicenter, double-blind, placebo-controlled, randomized study, consisting of a 6-week screening phase, a 13-week test phase, and a 4-week follow-up phase. Subjects/setting Subjects with type 2 diabetes (age range 31 to 70 years) entered the test phase of this study; 128 subjects completed the study. The subjects were recruited from 5 medical centers across the United States and were, on average, obese. Intervention Subjects were randomly assigned to receive either placebo (cellulose) capsules (n=69) or 667 mg encapsulated sucralose (n=67) daily for the 13-week test phase. All subjects blindly received placebo capsules during the last 4 weeks of the screening phase and for the entire 4-week follow-up phase. Main outcome measures Glycated hemoglobin (HbA1c), fasting plasma glucose, and fasting serum C-peptide were measured approximately every 2 weeks to evaluate blood glucose homeostasis. Data were analyzed by analysis of variance using repeated measures. Results There were no significant differences between the sucralose and placebo groups in HbA1c, fasting plasma glucose, or fasting serum C-peptide changes from baseline. There were no clinically meaningful differences between the groups in any safety measure. Conclusions This study demonstrated that, similar to cellulose, sucralose consumption for 3 months at doses of 7.5 mg/kg/day, which is approximately three times the estimated maximum intake, had no effect on glucose homeostasis in individuals with type 2 diabetes. Additionally, this study showed that sucralose was as well-tolerated by the study subjects as was the placebo.

Excessive circulating large molecular weight immunoreactive glucagon components in subjects with the idiopathic postprandial syndrome.

The glucagon RIA measures several molecular components in human plasma. Clinical disorders have been described associated with abnormal elevations of certain of these components. This report documents another clinical disorder, the idiopathic postprandial syndrome, which also appears associated with excessive circulating large molecular weight immunoreactive glucagon (IRG) components. During studies of glucose homeostasis in subjects with apparent idiopathic postabsorptive hypoglycemia, 80 subjects were evaluated using oral glucose tolerance tests; 18 subjects were found to have clinical and laboratory findings consistent with the disorder, and of these, 3 had markedly elevated basal total plasma IRG levels. Plasma IRG responses in the subjects after oral glucose or mixed meals were variable. Physical characterization of the excessive large molecular weight IRG components revealed molecular weight estimates of 300,000 and 345,000 daltons in 2 subjects and of more than 200,000 daltons in the third subject. The origin and chemical nature of this material is uncertain. None of these subjects had evidence for a glucagonoma, as supported by the virtual absence of detectable levels of native (3500-dalton) glucagon after gel filtration. Since the origin of the idiopathic postprandial syndrome as well as the origin and chemical nature of large molecular weight IRG components are unknown, the association of these two findings remains unclear but is clinically important in the differential diagnosis of the glucagonoma syndrome.