Postprandial Glucose Tolerance Research Articles

Dilemma in Diabetes Care Relates to Its Complications: Strategies for Prevention

The dilemma concerning the prevailing classification of Type 1 and Type 2 diabetes is a serious hindrance to effective diabetes care. Many patients who are classified with Type 2 diabetes have symptoms and require treatment similar to those classified with Type 1 diabetes. In addition, patients are often diagnosed with diabetes as a result of elevated fasting blood glucose instead of 2-hour postprandial glucose levels or oral glucose tolerance tests. The misdiagnosis of diabetes accompanied by prescription of oral hypoglycemic agents or antihypertensive therapy, have caused unwarranted health problems in people who may not have diabetes. In this article, patients are presented who illustrate the misdiagnosis of diabetes and the need of proper testing to uncover diabetes. Additional case histories indicate the effect that oral hypoglycemic agents and antihypertensive medications may have on patient health. Suggestions are made regarding proper diagnosis and care. In patients with established diabetes, adequate control of glycemia with insulin, diet restriction and weight reduction, fundamental to prevention of microvascular and macrovascular complications, is stressed. Hospitalizations are preventable if professionals spend time explaining details of diabetic care to patients thereby enabling them to take full responsibility of their illness. Glucose control with insulin therapy, concomitantly with means for weight reduction in obese individuals, must be discussed in a repetitive fashion with the patient. Uncontrolled diabetes, resulting in frequent hospitalizations for a variety of complications, has markedly escalated the cost of diabetic care. Patient education and cooperation are the cornerstone of successful diabetes therapy and the mainstay of prevention of diabetes complications. Thereby, the cost of diabetes care will be reduced. The classification of Type 1 and Type 2 diabetes conveys little to the patients about diabetes which is a potentially devastating disease, nevertheless, with full attention to glucose control, healthy living is attainable. Utmost care should be taken to identify if the person does or does not have diabetes by appropriate testing and attention to proper therapy.

The Clinical Significance of HbA1c as a Predictive Factor for Abnormal Postprandial Glucose Metabolism in NAFLD Patients with an Elevated Liver Chemistry

NAFLD patients often show normal fasting glucose levels despite having abnormal postprandial glucose levels. This study is aimed at examining the possibility of utilizing HbA1c as a surrogate marker for abnormal glucose tolerance in NAFLD. This study was conducted on ninety-one NAFLD patients exhibiting elevated liver enzyme. Oral glucose tolerance tests (OGTT) (75g) were performed. Insulin concentrations were measured in a fasting state, and again at 120 minutes. Sixteen subjects (44.7%) showed abnormal postprandial glucose levels among subjects with normal fasting glucose level (<100mg/dL). Among subjects whose fasting glucose levels were within the 100-125mg/dL range, 30 patients (68.2%) showed abnormal OGTT findings and 13 patients (29.5%) were diagnosed as diabetics. In univariate analysis, the predictive factors for abnormal glucose tolerance were found to be HbA1c, age, fasting glucose and 120-minute insulin. However, in multivariate analysis, only HbA1c was found to be a significant predictive factor ((β)=0.43, p=0.017). The mean values for HbA1c were higher in the diabetes (6.2%) and glucose intolerance groups (5.8%) than in the normal group (5.5%). Using HbA1c 5.8% as the cut-off level in AUROC, sensitivity and specificity for predicting abnormal OGTT were 71.0% and 89.9%. Of NAFLD patients who showed HbA1c concentrations of 5.8% or higher, 90.9% showed abnormal OGTT. In NAFLD patients, an HbA1c concentration of 5.8% or higher can be used as an index for predicting abnormal postprandial glucose tolerance.

Do entero-pancreatic neurons contribute to overall insulin sensitivity in pig?

The entero-pancreatic (EP) neurons directly link the proximal duodenum to the pancreas and participate to the pre absorptive phase of postprandial insulin secretion. EP neurons may therefore play a critical role in the postprandial inhibition of hepatic gluconeogenesis mandatory for an adequate postprandial glucose tolerance and a good overall insulin sensitivity. To test this hypothesis, modified oral glucose tolerance tests (mOGTT) were performed every 2 months for 6 months in intact (n = 3) and EP denervated minipigs (n = 4). An euglycemic hyperinsulinemic clamp procedure (EHC) was performed at the end of the experiment to estimate insulin sensitivity. EP denervation was achieved by sectioning the connective tissue between the pancreas and the proximal duodenum. The mOGGT consisted in the standard daily ration plus 1.5 g of glucose per kg of body weight. Postprandial glycemia and insulinemia were not affected by the EP denervation ( P = 0.86 and P = 0.46 for glycemia and insulinemia respectively). The insulinogenic index (ISI = AUC insulin/AUC glucose) was not significantly different in IEP and XEP animals either ( P = 0.13). The final EHC highlighted a tendency for XEP to be less insulin sensitive than IEP ( P = 0.09). We concluded that EP neurons were not mandatory for an adequate postprandial glucose tolerance but might contribute to the overall insulin sensitivity in pigs.

Blood sugar measurement in zebrafish reveals dynamics of glucose homeostasis.

The adult zebrafish has the potential to become an important model for diabetes-related research. To realize this potential, small-scale methods for analyzing pancreas function are required. The measurement of blood glucose level is a commonly used method for assessing beta-cell function, but the small size of the zebrafish presents challenges both for collecting blood samples and for measuring glucose. We have developed methods for collecting microsamples of whole blood and plasma for the measurement of hematocrit and blood glucose. We demonstrate that two hand-held glucose meters designed for use by human diabetics return valid results with zebrafish blood. Additionally, we present methods for fasting and for performing postprandial glucose and intraperitoneal glucose tolerance tests. We find that the dynamics of zebrafish blood glucose homeostasis are consistent with patterns reported for other omnivorous teleost fish.

Bile-induced secretion of glucagon-like peptide-1: pathophysiological implications in type 2 diabetes?

During the last decades it has become clear that bile acids not only act as simple fat solubilizers, but additionally represent complex hormonal metabolic integrators. Bile acids activate both nuclear receptors (controlling transcription of genes involved in for example bile acid, cholesterol, and glucose metabolism) and the cell surface G protein-coupled receptor TGR5 (modulating energy expenditure in brown fat and muscle cells). It has been shown that TGR5 is expressed in enteroendocrine L cells, which secrete the potent glucose-lowering incretin hormone glucagon-like peptide-1 (GLP-1). Recently it was shown that bile acid-induced activation of TGR5 results in intestinal secretion of GLP-1 and that enhanced TGR5 signaling improves postprandial glucose tolerance in diet-induced obese mice. This Perspectives article presents these novel findings in the context of prior studies on nutrient-induced GLP-1 secretion and outlines the potential implications of bile acid-induced GLP-1 secretion in physiological, pathophysiological, and pharmacological perspectives.

Daytime variability of postprandial glucose tolerance and pancreatic B‐cell function using 12‐h profiles in persons with Type 2 diabetes

To study the variation in daytime glucose tolerance and pancreatic B-cell function at different levels of glycated haemoglobin (HbA(1c)) in subjects with Type 2 diabetes (T2DM). T2DM subjects (n = 49; 34 men) had 12-h daytime plasma glucose (PG), insulin (PI), total (PTp) and intact proinsulin (PIp) profiles determined in response to three identical test meals at 4-h intervals. Subjects were divided into three groups according to HbA(1c)--group 1: < 7.3% (n = 18); group 2: 7.3-8.0% (n = 17); group 3: > 8.0% (n = 14). Fasting and preprandial (prior to meals 2 and 3) concentrations, total area under the curve (AUC), AUC above fasting (dAUC) and maximum postprandial metabolic concentrations (C(max)) were compared between the three meals and across the groups. Subjects in group 1 had significantly higher fasting plasma glucose (FPG) compared with preprandial PG concentrations (7.1 +/- 0.2 vs. 5.9 +/- 0.3 vs. 5.4 +/- 0.2; P < 0.01). Subjects in groups 2 and 3 had significantly higher FPG compared with preprandial PG levels prior to meal 3. PG.dAUC was highest in response to meal 1 and lowest following meal 2 (P < 0.05). FPI concentrations were significantly lower compared with preprandial PI concentrations. Subjects in group 1 had significantly higher PI prior to meal 2 compared with meal 3. PI.dAUC was highest in response to meal 1. Subjects in group 1 had lowest PI.dAUC following meal 2. FTp and FIp concentrations were also significantly lower compared with preprandial concentrations. PTp.dAUC and PIp.dAUC was highest in response to meal 1. There appears to be a shift in diurnal variation in glucose homeostasis and pancreatic B-cell function. Subjects had decreased glucose tolerance in response to the first and third meal of the day irrespective of glycaemic control. The variability in glucose tolerance was reflected by both quantitative and qualitative dysfunction of the pancreatic B-cell.

Postprandial Diabetic Glucose Tolerance Is Normalized by Gastric Bypass Feeding as Opposed to Gastric Feeding and Is Associated With Exaggerated GLP-1 Secretion

OBJECTIVETo examine after gastric bypass the effect of peroral versus gastroduodenal feeding on glucose metabolism.RESEARCH DESIGN AND METHODSA type 2 diabetic patient was examined on 2 consecutive days 5 weeks after gastric bypass. A standard liquid meal was given on the first day into the bypassed gastric remnant and on the second day perorally. Plasma glucose, insulin, C-peptide, glucagon, incretin hormones, peptide YY, and free fatty acids were measured.RESULTSPeroral feeding reduced 2-h postprandial plasma glucose (7.8 vs. 11.1 mmol/l) and incremental area under the glucose curve (iAUC) (0.33 vs. 0.49 mmol · l−1 · min−1) compared with gastroduodenal feeding. β-Cell function (iAUCCpeptide/Glu) was more than twofold improved during peroral feeding, and the glucagon-like peptide (GLP)-1 response increased nearly fivefold.CONCLUSIONSImprovement in postprandial glucose metabolism after gastric bypass is an immediate and direct consequence of the gastrointestinal rearrangement, associated with exaggerated GLP-1 release and independent of changes in insulin sensitivity, weight loss, and caloric restriction.

Foxo1 integrates insulin signaling with mitochondrial function in the liver

Type 2 diabetes is a complex disease that is marked by the dysfunction of glucose and lipid metabolism. Hepatic insulin resistance is especially pathogenic in type 2 diabetes, as it dysregulates fasting and postprandial glucose tolerance and promotes systemic dyslipidemia and nonalcoholic fatty liver disease. Mitochondrial dysfunction is closely associated with insulin resistance and might contribute to the progression of diabetes. Here we used previously generated mice with hepatic insulin resistance owing to the deletion of the genes encoding insulin receptor substrate-1 (Irs-1) and Irs-2 (referred to here as double-knockout (DKO) mice) to establish the molecular link between dysregulated insulin action and mitochondrial function. The expression of several forkhead box O1 (Foxo1) target genes increased in the DKO liver, including heme oxygenase-1 (Hmox1), which disrupts complex III and IV of the respiratory chain and lowers the NAD(+)/NADH ratio and ATP production. Although peroxisome proliferator-activated receptor-gamma coactivator-1alpha (Ppargc-1alpha) was also upregulated in DKO liver, it was acetylated and failed to promote compensatory mitochondrial biogenesis or function. Deletion of hepatic Foxo1 in DKO liver normalized the expression of Hmox1 and the NAD(+)/NADH ratio, reduced Ppargc-1alpha acetylation and restored mitochondrial oxidative metabolism and biogenesis. Thus, Foxo1 integrates insulin signaling with mitochondrial function, and inhibition of Foxo1 can improve hepatic metabolism during insulin resistance and the metabolic syndrome.

Tube feeding with a diabetes-specific feed for 12 weeks improves glycaemic control in type 2 diabetes patients

Assess longer-term (12 weeks) effects of a diabetes-specific feed on postprandial glucose response, glycaemic control (HbA1c), lipid profile, (pre)-albumin, clinical course and tolerance in diabetic patients. In this randomized, controlled, double-blind, parallel group study 25 type 2 diabetic patients on tube feeding were included. Patients received a soy-protein based, multi-fibre diabetes-specific feed or isocaloric, fibre-containing standard feed for 12 weeks, while continuing on their anti-diabetic medication. At the beginning, after 6 and 12 weeks, several (glycaemic) parameters were assessed. The postprandial glucose response (iAUC) to the diabetes-specific feed was lower at the 1st assessment compared with the standard feed (p=0.008) and this difference did not change over time. HbA1c decreased over time in the diabetes-specific and not in the standard feed group (treatment*time:p=0.034): 6.9+/-0.3% (mean+/-SEM) at baseline vs. 6.2+/-0.4% at 12 weeks in the diabetes-specific group compared to 7.9+/-0.3% to 8.7+/-0.4% in the standard feed group. No significant treatment*time effect was found for fasting glucose, insulin, (pre-) albumin or lipid profile, except for increase of HDL in the diabetes-specific group. The diabetes-specific feed studied significantly improved longer-term glycaemic control in diabetic patients. This was achieved in addition to on-going anti-diabetic medication and may affect clinical outcome.

Improvement of postprandial lipid handling and glucose tolerance in a non-diabetic population by the dual PPARα/γ agonist, tesaglitazar

This study examined the effect of tesaglitazar (GALIDA), a dual peroxisome proliferator-activated receptor (PPAR)alpha/gamma agonist, on postprandial metabolism. This investigation was part of the Study in Insulin Resistance (SIR) (SH-SBT-0001), a randomised, double-blind, placebo-controlled study that reported improvements in fasting lipid and glucose values with tesaglitazar (0.1, 0.25, 0.5 or 1 mg once daily for 12 weeks) in hypertriglyceridaemic, abdominally obese, non-diabetic patients. A subgroup of 222 patients underwent postprandial lipid and glucose testing at baseline and treatment end. Tesaglitazar 0.25, 0.5 and 1 mg reduced postprandial area under the curve (AUC) for triglycerides by 20% (p=0.003), 30% (p<0.0001) and 41% (p<0.0001), respectively. Free fatty acid (FFA) levels were reduced by 17% with tesaglitazar 0.5 mg (p=0.002) and by 29% with tesaglitazar 1 mg (p<0.0001). Tesaglitazar significantly improved glucose tolerance and increased the proportion of patients with normal glucose tolerance as measured by the oral glucose tolerance test (OGTT). To conclude, postprandial dyslipidaemia and hyperglycaemia, indicators of increased vascular risk, were significantly improved by tesaglitazar treatment in these non-diabetic, hypertriglyceridaemic, abdominally obese subjects.

EFFECTS OF AGAR AND PECTIN ON GASTRIC EMPTYING AND POST‐PRANDIAL GLYCAEMIC PROFILES IN HEALTHY HUMAN VOLUNTEERS

1. Dietary fibre, such as pectin, delays gastric emptying and may enhance post-prandial glucose tolerance. Agar, which is high in fibre content, is widely used in the traditional Japanese diet. Although long-term diet therapy with agar decreases fasting plasma glucose levels in diabetes, knowledge is lacking about the acute effects of agar on gastric emptying and the post-prandial glycaemic profiles. The present study was designed to investigate the acute effects of agar. 2. Ten healthy male volunteers were studied on three occasions with three different test meals (450 kcal/500 mL): (i) a fibre-free meal; (ii) a meal with 2.0 g agar; or (iii) a meal with 5.2 g pectin. On each occasion, participants underwent a [(13)C]-acetate breath test along with serial blood sampling. To quantify gastric emptying, the half [(13)CO(2)] excretion time (t((1/2)b)) and the time for maximal [(13)CO(2)] excretion rate (t(lag)) were determined. The post-prandial glycaemic response was expressed as an incremental change from the fasting value at each sampling time. Data were analysed using repeated-measures analysis of variance (anova), followed by a post hoc paired Student's t-test with Bonferroni adjustment. 3. The time-course for respiratory [(13)CO(2)] excretion differed significantly among the three test meals (P = 0.0004, anova). Compared with the control meal, [(13)CO(2)] excretion was significantly lower following consumption of the agar meal (between 40 and 105 min post-prandially; P < 0.025, Student's t-test) and the pectin meal (between 40 and 180 min post-prandially; P < 0.025, Student's t-test). Among the three meals, significant differences were found in t((1/2)b) (P = 0.002, anova) and t(lag) (P = 0.011, anova). Compared with the control meal, the agar and pectin meals exhibited a significantly prolonged t((1/2)b) (P = 0.007 and P < 0.0001, respectively, Student's t-test) and t(lag) (P = 0.006 and P = 0.002, respectively, Student's t-test). Neither the agar nor pectin meal affected the post-prandial glucose profile. 4. In healthy adults, agar and pectin delay gastric emptying but have no impact on the post-prandial glucose response.

The Effect of Insulin Antibodies on the Metabolic Action of Inhaled and Subcutaneous Insulin

To assess the impact of the development of high- or low-affinity insulin antibodies (IABs) on postprandial glucose tolerance, duration of insulin action, and clinical safety in patients with type 1 diabetes receiving inhaled insulin (Exubera). This study consisted of a prospective, randomized, open-label, parallel-group trial in which 47 patients with type 1 diabetes received NPH insulin twice daily plus either premeal inhaled insulin (INH group; n = 24) or pre-meal subcutaneous regular insulin (SC group; n = 23) for 24 weeks. Meal challenge and euglycemic clamp studies were performed on consecutive days at baseline, week 12, and week 24. Adverse events were monitored. For the INH and SC groups, mean (+/-SD) IAB levels were 3.5 +/- 3.9 and 2.6 +/- 4.1 muU/ml at baseline, respectively, compared with 101.4 +/- 140.4 and 4.3 +/- 9.4 microU/ml at week 24. At week 24, the changes from baseline were similar for the INH and SC groups for maximal plasma glucose concentration (C(max)) (adjusted ratio for treatment group difference 0.99 [90% CI 0.95-1.03]), area under the plasma glucose concentration time curve (adjusted ratio for treatment group difference 0.98 [0.88-1.08]), and duration of insulin action (adjusted treatment group difference 29 min [-49 to 108]). No adverse events were attributed to IABs. In patients with type 1 diabetes treated with inhaled insulin, development of high- or low-affinity IABs did not impair postprandial glucose tolerance, alter the time-action profile of insulin, or impact tolerability. No clinical relevance of IABs was identified in this study.

The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia.

We studied the mechanisms and physiological relevance of the cephalic insulin response to meal ingestion in 12 healthy women (age 63 +/- 0.4 years; BMI 27.7 +/- 1.7 kg/m2). The ganglionic antagonist, trimethaphan, which impairs neurotransmission across parasympathetic and sympathetic autonomic ganglia, or atropine or saline was given intravenously during the first 15 min after ingestion of a standard meal (350 kcal). During saline infusion, insulin levels increased during the first 10 min after meal ingestion, whereas the first increase in glucose was evident at 15 min. The preabsorptive 10-min insulin response was reduced by 73 +/- 11% by trimethaphan (P = 0.009), accompanied by impaired reduction of glucose levels from 25 to 60 min after meal ingestion (deltaglucose = -1.27 +/- 0.5 [with saline] vs. 0.1 +/- 0.4 mmol/l [with trimethaphan]; P = 0.008). This reduction at 25-60 min in glucose levels correlated significantly to the 10-min insulin response (r = 0.65, P = 0.024). The 10-min insulin response to meal ingestion was also reduced by atropine, but only by 20 +/- 9% (P = 0.045), which was lower than the reduction with trimethaphan (P = 0.004). The preabsorptive insulin response was not accompanied by any increase in circulating levels of gastric inhibitory polypeptide (GIP) or glucagon-like peptide 1 (GLP-1). In conclusion, 1) the early preabsorptive insulin response to meal ingestion in humans can be largely attributed to autonomic activation mediated by noncholinergic and cholinergic mechanisms, 2) this cephalic insulin response is required for a normal postprandial glucose tolerance, and 3) GIP and GLP-1 do not contribute to the preabsorptive cephalic phase insulin response to meal ingestion.

Type I diabetes manifested solely by 2-h oral glucose tolerance test criteria.

The clinical presentation of type 1 diabetes usually involves symptoms such as polyuria and polydipsia. However, investigators in the Diabetes Prevention Trial of Type 1 Diabetes (DPT-1) have detected a group of subjects with type 1 diabetes who have a different phenotype. These subjects are asymptomatic, have normal (<6.1 mmol/l) (group A) or impaired (6.1- <7.0 mmol/l) (group B) fasting glucose, but have 2-h glucose values >11.1 mmol/l on their oral glucose tolerance tests (OGTT). Of the 585 OGTTs performed on islet cell antibody (ICA)-positive relatives with insulin autoantibodies (IAA) or low first-phase insulin response (FPIR), normal glucose tolerance (NGT) was found in 427 subjects; impaired glucose tolerance (IGT) was found in 87 subjects, and diabetes was found by 2-h OGTT criteria alone in 61 subjects. Despite marked differences in 2-h glucose values (NGT 5.8 +/- 1.1 mmol/l, IGT 8.9 +/- 0.9 mmol/l, and group A 13.5 +/- 2.5 mmol/l), there were no significant differences in fasting glucose values among NGT (4.8 +/- 0.5 mmol/l), IGT (5.03 +/- 0.5 mmol/l), and group A (4.99 +/- 0.7 mmol/l) categories. Mean FPIR was higher in subjects with NGT compared with subjects with IGT and subjects diagnosed by 2-h OGTT criteria alone. However, the correlation between FPIR and 2-h glucose value was low (r2 = 0.114). Multivariate analysis demonstrated that additional independent variables provide smaller contributions to the 2-h glucose value. In conclusion, there are asymptomatic type 1 diabetic subjects whose diabetes was diagnosed by the 2-h criteria on OGTT alone. Despite the importance of beta-cell dysfunction in the pathogenesis of type I diabetes, factors other than impaired FPIR must also contribute to postprandial glucose tolerance in these subjects.

Skeletal muscle glycogen content in patients with cirrhosis

We investigated stable cirrhotic patients for muscle glycogen content. Muscle biopsy samples were taken of 14 patients after overnight fasting. Electron microscopy showed normal intracellular distribution of glycogen (n = 8). Muscle glycogen concentration was 16.5 +/- 7.1 gm/kg wet muscle weight (normal range, 10 to 20 gm/kg). Basal, early postabsorptive, exercise-induced and insulin-induced respiratory quotients as well as insulin sensitivity (euglycemic clamp technique, 7.2 pmol insulin/kg body weight/min) and glucose tolerance were assessed. The glucose disposal rate was 23.0 +/- 10.1 mumol/kg/min (mean +/- S.D.), indicating moderate insulin resistance in these patients. We found no association between basal muscle glycogen content and basal or postprandial respiratory quotient, insulin sensitivity, nutritional status or glucose tolerance. However, there was a positive correlation between muscle glycogen content and exercise, as well as insulin-induced respiratory quotient (r = 0.651, p < 0.03 and r = 0.587, p < 0.03, respectively). We conclude that postabsorptive muscle glycogen stores, which are effectively maintained in patients with cirrhosis, are one determinant of exercise-induced and insulin-induced whole body fuel metabolism in these patients.

Skeletal muscle glycogen content in patients with cirrhosis

We investigated stable cirrhotic patients for muscle glycogen content. Muscle biopsy samples were taken of 14 patients after overnight fasting. Electron microscopy showed normal intracellular distribution of glycogen (n = 8). Muscle glycogen concentration was 16.5 ± 7.1 gm/kg wet muscle weight (normal range, 10 to 20 gm/kg). Basal, early postabsorptive, exercise-induced and insulin-induced respiratory quotients as well as insulin sensitivity (euglycemic clamp technique, 7.2 pmol insulin/kg body weight/min) and glucose tolerance were assessed. The glucose disposal rate was 23.0 ± 10.1 μmol/kg/min (mean ± S.D.), indicating moderate insulin resistance in these patients. We found no association between basal muscle glycogen content and basal or postprandial respiratory quotient, insulin sensitivity, nutritional status or glucose tolerance. However, there was a positive correlation between muscle glycogen content and exercise, as well as insulin-induced respiratory quotient (r = 0.651, p < 0.03 and r = 0.587, p < 0.03, respectively). We conclude that postabsorptive muscle glycogen stores, which are effectively maintained in patients with cirrhosis, are one determinant of exercise-induced and insulin-induced whole body fuel metabolism in these patients.

Long-term effects of guar gum in subjects with non-insulin-dependent diabetes mellitus

The effects of 15 g guar gum/d on glycemic control, lipids, and insulin secretion were studied in 15 (8 male, 7 female) diet-treated subjects with non-insulin-dependent diabetes mellitus for 48 wk. Mean age (+/- SD) was 60 +/- 2 y (range 45-70 y), body mass index (in kg/m2) 28.6 +/- 0.9 (range 21.6 +/- 39.2), and duration of diabetes 6 +/- 1 y (range 2-14 y). Guar gum was preceded and followed by 8-wk placebo periods. Guar gum improved long-term glycemic control, postprandial glucose tolerance and lipid concentrations. The C-peptide response to a test meal increased by time during guar gum treatment, whereas the insulin response remained unchanged. This indicates that insulin secretion is enhanced by guar gum as reflected by increased C-peptide. A decreased molar ratio of insulin to C-peptide suggests that guar gum may increase hepatic insulin extraction. In conclusion, guar gum has favorable long-term effects on glycemic control and lipid concentrations.

The acute effect of preprandial exogenous and endogenous sulphonylurea-stimulated insulin secretion on postprandial glucose excursions in patients with type 2 diabetes.

Sulphonylureas improve glucose tolerance by stimulating insulin secretion. Whether improved glucose tolerance results from enhanced early insulin release or greater total insulin secretion is not clear. Insulin response to a test meal in Type 2 diabetic subjects with and without a single dose (2.5 mg) of oral and intravenous glipizide were, therefore, measured. Intravenous glipizide enhanced early insulin release more than oral glipizide (134% and 80% vs control; p < 0.01), whereas total insulin release was equally improved (78% and 54% vs control; p < 0.01). Despite slight differences in insulin release, there was no difference in glucose tolerance (median area under concentration curve (AUC); 66.6 vs 61.9 mmol x min l-1; NS). The test meal was repeated after a bolus of intravenous insulin at the beginning of the meal. This allowed comparison of the effect of exogenous and endogenous insulin supply on postprandial glucose excursions. In spite of an early and fivefold larger rise in serum insulin after intravenous administration of the hormone than after intravenous glipizide (725% vs 134%; p < 0.01), postprandial glucose was no better than after glipizide (median AUC; 87.8 vs 66.6 mmol x min l-1; NS). In contrast, glucose tolerance was better after oral glipizide compared to intravenous insulin (median AUC; 61.9 vs 87.8 mmol x min l-1; p < 0.05). In conclusion, the total amount of insulin secreted seems more important than the timing of the insulin release for the postprandial glucose tolerance in Type 2 diabetic subjects. Neither endogenous nor peripheral premeal supply of insulin could normalize postprandial glucose excursions in patients with Type 2 diabetes.

The effect of soluble- and insoluble-fibre supplementation on post-prandial glucose tolerance, insulin and gastric inhibitory polypeptide secretion in healthy subjects

Six healthy non-obese male subjects were given three test meals containing 100 g carbohydrate and 1.5 g soluble paracetamol, supplemented on one occasion with 10 g guar gum and on another with 10 g sugarbeet fiber. A further six subjects were given the same test meal supplemented on one occasion with 10 g soya-bean-cotyledon fibre and on another, 5 g glucomannan. Venous blood samples were taken before, and at intervals for 180 min following the meal, and analysed for insulin, gastric inhibitory polypeptide (GIP) and paracetamol (as an index of gastric emptying). Arterialized blood samples were taken and analysed for glucose. Meal supplementation with both guar gum and sugar-beet fibre improved glucose tolerance, but circulating glucose levels were unaffected by the addition of either soya-bean-cotyledon fibre or glucomannan to the meals. Supplementation with guar gum and glucomannan lowered post-prandial insulin levels. Insulin levels were enhanced by addition of soya-bean-cotyledon fibre to the meal and unaffected by sugar-beet fibre. Post-prandial GIP levels were lowered in the guar-gum-supplemented meal and augmented with sugar-beet fibre supplementation. Addition of glucomannan and soya-bean-cotyledon fibre did not affect circulating GIP levels. The study failed to confirm previous reports of improved glucose tolerance following glucomannan and soya-bean-cotyledon fibre supplementation. The failure of sugar-beet fibre to reduce post-prandial insulin secretion despite improved glucose tolerance may be due to the observed increased secretion of GIP. The increased insulin levels seen following soya-bean-cotyledon fibre supplementation cannot be attributed either to changes in glucose tolerance, GIP secretion or gastric emptying.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Basal Insulin Supplementation on Disposition of Mixed Meal in Obese Patients With NIDDM

Basal insulin supplementation has been used as a therapy for patients with non-insulin-dependent diabetes mellitus (NIDDM) who require insulin. To determine whether basal insulin supplementation in addition to lowering postabsorptive plasma glucose concentration also improves the postprandial pattern of glucose disposition, glucose metabolism after ingestion of a solid mixed meal was assessed in obese patients with NIDDM before and after treatment with ultralente and compared with glucose metabolism observed in nondiabetic subjects. Splanchnic uptake of ingested glucose clearance was assessed by including [2-3H]glucose (a tracer that only minimally cycles through glycogen) in a solid mixed meal. Postprandial gluconeogenesis was estimated by measuring the rate of incorporation of carbon dioxide into glucose. Net glucose and lipid oxidation were measured by indirect calorimetry. Both splanchnic uptake of ingested glucose (27 +/- 1 vs. 14 +/- 2 g) and postprandial hepatic glucose release (51 +/- 5 vs. 24 +/- 3 g) were greater (P less than .001) in diabetic than in nondiabetic subjects. Although the percentage of postprandial hepatic glucose release accounted for by glucose synthesis from bicarbonate was similar in the two groups (25 +/- 2 vs. 35 +/- 5%), the absolute rate was greater in the diabetic patients (13 +/- 1 vs. 8 +/- 1 g; P less than .05). Postprandial glucose oxidation and glucose disposal (measured either isotopically or by the forearm-catheterization technique) were similar in both groups. However, total lipid oxidation was increased in the diabetic patients. (P less than .05). Two weeks of basal insulin supplementation lowered fasting glucose concentrations (from 219 +/- 22 to 144 +/- 21 mg/dl; P less than .01) and integrated postprandial glycemic response (from 814 +/- 68 to 621 +/- 72 min.mg.ml-1) but not to normal. Although circulating insulin concentrations were two- to threefold greater (P less than .02) after 3 mo of basal insulin supplementation, the postprandial pattern of glucose metabolism remained essentially the same. Basal insulin supplementation decreased (P less than .05) both splanchnic uptake of ingested glucose and hepatic glucose release. The addition of a preprandial injection of soluble insulin to basal insulin supplementation further suppressed (P less than .05) postprandial hepatic glucose release, thereby further improving postprandial glucose tolerance. These studies indicate that initial splanchnic glucose clearance, hepatic glucose release, and new glucose synthesis, as well as extrahepatic substrate metabolism, are altered in NIDDM after ingestion of a mixed meal.(ABSTRACT TRUNCATED AT 400 WORDS)