Peak Insulin Response Research Articles

Bidirectional Mendelian randomization study of insulin-related traits and risk of ovarian cancer.

It is well known that the occurrence and development of ovarian cancer are closely related to the patient's weight and various endocrine factors in the body. Mendelian randomization (MR) was used to analyze the bidirectional relationship between insulin related characteristics and ovarian cancer. The data on insulin related characteristics are from up to 5567 diabetes free patients from 10 studies, mainly including fasting insulin level, insulin secretion rate, peak insulin response, etc. For ovarian cancer, UK Biobank data just updated in 2021 was selected, of which the relevant gene data was from 199741 Europeans. Mendelian randomization method was selected, with inverse variance weighting (IVW) as the main estimation, while MR Pleiotropy, MR Egger, weighted median and other methods were used to detect the heterogeneity of data and whether there was multi validity affecting conclusions. Among all insulin related indicators (fasting insulin level, insulin secretion rate, peak insulin response), the insulin secretion rate was selected to have a causal relationship with the occurrence of ovarian cancer (IVW, P < 0.05), that is, the risk of ovarian cancer increased with the decrease of insulin secretion rate. At the same time, we tested the heterogeneity and polymorphism of this indicator, and the results were non-existent, which ensured the accuracy of the analysis results. Reverse causal analysis showed that there was no causal effect between the two (P>0.05). The impairment of the insulin secretion rate has a causal effect on the risk of ovarian cancer, which was confirmed by Mendel randomization. This suggests that the human glucose metabolism cycle represented by insulin secretion plays an important role in the pathogenesis of ovarian cancer, which provides a new idea for preventing the release of ovarian cancer.

Metabolomic Profiling in Response to an Oral Glucose Tolerance Test Reveals Pathways Associated With Obesity and Insulin Resistance During the Pubertal Transition

Abstract Objectives To reveal alterations in metabolic pathways in response to an oral glucose tolerance test (OGTT) underlying the development of insulin resistance during the pubertal transition. Methods Participants were recruited as healthy controls (HC, n = 55, aged 8.3–18.0 years, BMI percentile 5–85%) and overweight and obese individuals (OVOB, n = 228, aged 8.1–17.9 years, BMI percentile ≥ 85%). Participants were grouped based on their peak insulin response to the OGTT, stratified by peak at t30 (Group 1, n = 163), t60 (Group 2, n = 75), and t120 minutes (Group 3, n = 44). Untargeted metabolomics profiled 267 annotated metabolites and &amp;gt; 3000 unannotated features in plasma at t0 and t60 minutes. Regression classified changes in metabolites across the time-course, assessing the influence of BMI and insulin response (FDR &amp;lt; 0.05). The connectivity of the metabolome was determined using differential network enrichment analysis (DNEA), stratified by insulin response group. Results At fasting, 32% of the metabolites differed between HC and OVOB, including elevated kynurenine, leucine/isoleucine, methionine, tyrosine, short-chain acylcarnitines, and diacylglycerols in OVOB. At t60, only 4% of the metabolites differed between HC and OVOB participants, suggesting a “normalization” of the metabolome, with exceptions of acylcarnitines and FA oxidation (FAO) intermediates. Although no metabolites differed significantly between insulin response group, differential subnetworks were observed, including increased connectivity between FA and FAO intermediates in Group 1 at t60, suggesting differential regulation in post-prandial FAs. Conclusions Profiling the metabolome response to an OGTT may highlight metabolic dysfunction prior to type 2 diabetes and will be used in future longitudinal analyses predicting insulin resistance trajectory. Funding Sources The National Institute of Child Health and Human Development, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institutes of Health

Hypoglycemia in cystic fibrosis during an extended oral glucose tolerance test.

Hypoglycemia in cystic fibrosis (CF), in the absence of glucose-lowering therapies, has long been identified as an important issue in the management of CF. There is currently still no unifying hypothesis for its etiology. The aims of this study were to perform a 3-h oral glucose tolerance test (OGTT) in participants with CF and (1) document glucose, insulin, glucagon, glucagon-like-peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) release patterns within varying glucose tolerance groups during the OGTT; (2) determine the prevalence of hypoglycemic during the OGTT; and (3) define any association between hypoglycemia and patterns of insulin, glucagon, GLP-1, and GIP release. Eligible participants attending an adult CF clinic completed a 3-h OGTT. Hypoglycemia on OGTT was defined as mild (glucose 3.4-3.9 mmol/L), moderate (glucose 3.1-3.3 mmol/L), and severe (glucose ≤ 3 mmol/L). Hormones were measured at fasting, 30, 60, 120, and 180 min. Twenty-four participants completed the study, of which 7 had normal glucose tolerance, 12 had abnormal glucose tolerance, and 5 had cystic fibrosis related diabetes (CFRD). All participants had a delayed insulin response compared with normative data. All glucose tolerance groups showed appropriate and similar suppression of fasting glucagon. Four participants (17%) had mild hypoglycemic, three (13%) had moderate hypoglycemic, and eight (33%) had severe hypoglycemic. No participant with CFRD demonstrated hypoglycemic. Of the 19 participants without CFRD, 15 (79%) experienced hypoglycemic. Participants with hypoglycemic had greater peak glucose and insulin responses than those that did not have hypoglycemic, and this approached significance (p = .0625 for glucose and p = .0862 for insulin). No significant mean differences between GLP-1 and GIP release were found. There was no relationship between hypoglycemic and modulator therapy. Postprandial hypoglycemic was unmasked by the extension of an OGTT to 3 h. Delayed and abnormal insulin release, and ineffective counter-regulatory action of glucagon may have a role in its etiology.

Ghrelin in rat pancreatic islets decreases islet blood flow.

The peptide ghrelin is mainly produced in some of the epithelial cells in the stomach, but also, during starvation, by the ε-cells in the endocrine pancreas. Ghrelin, as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R1α), exerts a variety of metabolic functions including stimulation of appetite and weight gain. Its complete role is not yet fully understood, including whether it has any vascular functions. The present study evaluated if ghrelin affects pancreatic and islet blood flow. Ghrelin and the GHS-R1α receptor antagonist GHRP-6 were injected intravenously in rats followed by blood flow measurements using a microsphere technique. Ghrelin decreased, while GHRP-6 in fasted, but not fed, rats selectively increased islet blood flow fourfold. GHS-R1α was identified not only on glucagon-producing cells but also seemed to be present in the islet arterioles. GHRP-6 in fasted rats, only, also improved the peak insulin response to glucose in vivo, thereby substantially blunting the hyperglycemia. GHRP-6 doubled glucose-stimulated insulin release in vitro of both islets obtained from fed and fasted rats. Our results indicate a novel role for endogenous ghrelin acting directly or indirectly as a local vasoconstrictor in the islets during fasting, thereby restricting the insulin response to hyperglycemia. This is to the best of our knowledge the first report that shows this physiological mechanism to restrict insulin delivery from the islets by acting on the vasculature; a mode of action that can be envisaged to complement the previously well-described mechanisms of ghrelin acting directly on the islet endocrine cells.

Protein supplementation enhances cerebral oxygenation during exercise in elite basketball players.

The aim of the present study was to examine cerebral oxygenation during high-intensity exercise in elite basketball players who consumed supplements with different whey protein contents after a short postexercise recovery to determine whether changing whey protein content in carbohydrate-based supplementation influences cerebral hemodynamic response when the supplement was consumed during a 2-h recovery after a 1-h exercise challenge. This was a randomized, counterbalanced crossover study. Fifteen Division 1 collegiate basketball players (18-20 y) consumed 6.25 kcal/kg of either high-protein (36% protein in total calorie) or an isocaloric low-protein (12% protein in total calorie) control supplement in a carbohydrate-based drink immediately after a 1-h cycling (70% of maximal oxygen consumption [VO2max]). After a 2-h rest, the athletes were challenged on a cycloergometer at 80% VO2max. Blood perfusion (total hemoglobin) and oxygen saturation of frontal brain were continuously measured by near-infrared spectroscopy during the cycling. Before the cycloergometer test, high-protein supplementation increased peak insulin response and lowered glucose increases during the recovery compared with the low-protein trial. High-protein supplementation enhanced increases in cerebral oxygen saturation (P < 0.01) and attenuated increases in cerebral blood perfusion (total hemoglobin; P < 0.01) during the cycloergometer exercise; and resulted in a 16% longer cycling time (from 474 ± 49 s to 553 ± 78 s, P < 0.05), compared with the low-protein trial. Enhanced fatigue recovery after consumption of a high-protein supplement is associated with enhanced cerebral oxygenation against exercise challenge, which spares brain blood demand for periphery.

The effects of added whey protein to a pre-operative carbohydrate drink on glucose and insulin response.

Pre-operative complex carbohydrate (CHO) drinks are recommended to attenuate post-operative insulin resistance. However, many institutions use simple CHO drinks, which while convenient, may have less metabolic effects. Whey protein may enhance insulin release when added to complex CHO. The aim of this study was to compare the insulin response to simple CHO vs. simple CHO supplemented with whey protein. Twelve healthy volunteers participated in this double-blinded, within subject, cross-over design study investigating insulin response to simple CHO drink vs. simple CHO+whey (CHO+W) drink. The primary outcome was the accumulated insulin response during 180min after ingestion of the drinks (Area under the curve, AUC). Secondary outcomes included plasma glucose and ghrelin levels, and gastric emptying rate estimated by acetaminophen absorption technique. Data presented as mean (SD). There was no differences in accumulated insulin response after the CHO or CHO+W drinks [AUC: 15 (8) vs. 20 (14)nmol/l, P=0.27]. Insulin and glucose levels peaked between 30 and 60min and reached 215 (95)pmol/l and 7 (1)mmol/l after the CHO drink and to 264 (232)pmol/l and 6.5 (1)mmol/l after the CHO+W drink. There were no differences in glucose or ghrelin levels or gastric emptying with the addition of whey. The addition of whey protein to a simple CHO drink did not change the insulin response in healthy individuals. The peak insulin responses to simple CHO with or without whey protein were lower than that previously reported with complex CHO drinks. The impact of simple carbohydrate drinks with lower insulin response on peri-operative insulin sensitivity requires further study.

A Genome-Wide Association Study of IVGTT-Based Measures of First-Phase Insulin Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants.

Understanding the physiological mechanisms by which common variants predispose to type 2 diabetes requires large studies with detailed measures of insulin secretion and sensitivity. Here we performed the largest genome-wide association study of first-phase insulin secretion, as measured by intravenous glucose tolerance tests, using up to 5,567 individuals without diabetes from 10 studies. We aimed to refine the mechanisms of 178 known associations between common variants and glycemic traits and identify new loci. Thirty type 2 diabetes or fasting glucose–raising alleles were associated with a measure of first-phase insulin secretion at P < 0.05 and provided new evidence, or the strongest evidence yet, that insulin secretion, intrinsic to the islet cells, is a key mechanism underlying the associations at the HNF1A, IGF2BP2, KCNQ1, HNF1B, VPS13C/C2CD4A, FAF1, PTPRD, AP3S2, KCNK16, MAEA, LPP, WFS1, and TMPRSS6 loci. The fasting glucose–raising allele near PDX1, a known key insulin transcription factor, was strongly associated with lower first-phase insulin secretion but has no evidence for an effect on type 2 diabetes risk. The diabetes risk allele at TCF7L2 was associated with a stronger effect on peak insulin response than on C-peptide–based insulin secretion rate, suggesting a possible additional role in hepatic insulin clearance or insulin processing. In summary, our study provides further insight into the mechanisms by which common genetic variation influences type 2 diabetes risk and glycemic traits.

Impact of polyphenol-rich sources on acute postprandial glycaemia: a systematic review.

Increasingly, evidence suggests a role for polyphenols in blood glucose control. The objective of this systematic review was to evaluate the effect of polyphenol-rich sources in combination with carbohydrate sources on resulting postprandial glycaemic and insulin responses. A literature search was conducted using Medline, CINHAL and Web of Science databases. Selected studies included randomised controlled trials in which the association of polyphenol-containing food or beverage consumption with a carbohydrate source and effect on acute postprandial glycaemia and/or insulin was reported. A total of thirteen full articles were included in the review. Polyphenol sources included coffee, black tea, fruit juice, plant extracts, berries and different rye breads, and carbohydrate sources included bread, pancakes and simple sugars such as sucrose, glucose and fructose. Although glycaemic and insulin responses differed depending on the polyphenol-carbohydrate combination, overall, polyphenol sources were shown to reduce the peak and early-phase glycaemic response and maintain the glycaemic response in the later stages of digestion. To a lesser extent, polyphenol sources were also shown to reduce peak insulin response and sustain the insulin response, especially when consumed with bread. This review supports epidemiological data suggesting that polyphenols in foods and beverages may have a beneficial effect on reducing the risk of type 2 diabetes. However, the extent of this effect is variable depending on the polyphenol and carbohydrate source.

The structure of wheat bread influences the postprandial metabolic response in healthy men.

Postprandial high glucose and insulin responses after starchy food consumption, associated with an increased risk of developing several metabolic diseases, could possibly be improved by altering food structure. We investigated the influence of a compact food structure; different wheat products with a similar composition were created using different processing conditions. The postprandial glucose kinetics and metabolic response to bread with a compact structure (flat bread, FB) was compared to bread with a porous structure (control bread, CB) in a randomized, crossover study with ten healthy male volunteers. Pasta (PA), with a very compact structure, was used as the control. The rate of appearance of exogenous glucose (RaE), endogenous glucose production, and glucose clearance rate (GCR) was calculated using stable isotopes. Furthermore, postprandial plasma concentrations of glucose, insulin, several intestinal hormones and bile acids were analyzed. The structure of FB was considerably more compact compared to CB, as confirmed by microscopy, XRT analysis (porosity) and density measurements. Consumption of FB resulted in lower peak glucose, insulin and glucose-dependent insulinotropic polypeptide (ns) responses and a slower initial RaE compared to CB. These variables were similar to the PA response, except for RaE which remained slower over a longer period after PA consumption. Interestingly, the GCR after FB was higher than expected based on the insulin response, indicating increased insulin sensitivity or insulin-independent glucose disposal. These results demonstrate that the structure of wheat bread can influence the postprandial metabolic response, with a more compact structure being more beneficial for health. Bread-making technology should be further explored to create healthier products.

A critical appraisal of antihyperglycemic and cardioprotective activities of liraglutide: A glucagon-like peptide-1 analog

Diabetes is leading cause for cardiovascular complication, drugs having cardioprotective and antihyperglycemic actions are constantly in search. Oral glucose elicits a three to four times higher peak insulin response compared with an equivalent dose of glucose, if infused intravenously. This is due to the reasons behind, the oral glucose causes a secretion of gut hormones, mainly the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) which enhance the glucose-induced insulin release. In patients with type 2 diabetes mellitus (type 2 DM), glucose-induced insulin release is unsatisfactory or absent. Because of this type 2 DM patients are unable to adjust their insulin secretion as per the need exist. GLP-1 secretion (but not GIP secretion) is diminished in patients with type 2 diabetes. However, when the GLP-1 and GIP agonist are administered in patients with type 2 diabetes, they elicit insulin secretion resulting in lowering of blood glucose level. In addition to its insulin stimulatory effect, GLP-1 agonist also induces cardioprotective effects. It increases nuclear respiratory factor-2 (Nrf2) and heamoxigenase-1(Ho-1) in cell which have antioxidant and cardioprotective property. GLP-1 maintains islets integrity and reduces apoptotic cell death of human islet cells in culture. Improved understanding of the mechanism of action and clinical effects of incretin-based therapies would be useful in advancement of its appropriate use in clinical practices.

Short communication: Relationship between competitive success during displacements at an overstocked feed bunk and measures of physiology and behavior in Holstein dairy cattle

The objective of this study was to evaluate how behavioral and physiological parameters are affected based on a cow's level of success at displacing others at an overstocked feed bunk. Forty Holstein nonlactating, late-gestation dairy cattle were housed in an overstocked pen [5 stalls/10 cows and 0.34m of linear feed bunk (FB) space/cow] in groups of 10 (4 heifers and 6 multiparous cows) for 14d. Plasma nonesterified fatty acids, glucose, and fecal cortisol metabolites (11,17-dioxoandrostanes) were measured in blood and feces sampled every 2d. A glucose tolerance test and an ACTH challenge were conducted on all cows on d 13 and 14, respectively to further explore the effects of competitive success on energy metabolism and stress physiology. Feeding behavior and displacements at the FB were recorded between d 7 to 10 of the observation period. A competition index (CInd) was calculated for each cow by dividing the number of times the cow displaced another at the FB by the total number of displacements the cow was involved in, either as an actor or reactor. Cows were then divided into 3 subgroups based on their CInd: high success (HS: CInd ≥0.6), medium success (0.4 ≤ CInd <0.6), and low success (LS: CInd <0.4). Heifers accounted for 7, 36, and 79% of the total number of animals in the HS (n=15), medium success (n=11), and LS (n=14) groups, respectively. No differences were observed in daily feeding time, total number of displacements, and time to approach the FB following fresh feed delivery between the 3 CInd groups; however, cows in the LS group had greater daily nonesterified fatty acid and 11,17-dioxoandrostane concentrations relative to cows in the HS group. No differences existed in cortisol response to an ACTH stimulation test between CInd categories. During the glucose tolerance test, glucose response curves were the same between all 3 CInd categories; however, the peak insulin response of LS cows was 130μIU/mL greater than the peak HS response, indicating that LS cows may have decreased tissue responses to insulin or increased pancreatic responses to glucose. In an overstocked environment, dairy cattle physiology is associated with a cow's level of success at displacing other individuals at the feed bunk.

Synergism by individual macronutrients explains the marked early GLP-1 and islet hormone responses to mixed meal challenge in mice

Apart from glucose, proteins and lipids also stimulate incretin and islet hormone secretion. However, the glucoregulatory effect of macronutrients in combination is poorly understood. We therefore developed an oral mixed meal model in mice to 1) explore the glucagon-like peptide-1 (GLP-1) and islet hormone responses to mixed meal versus isocaloric glucose, and 2) characterize the relative contribution of individual macronutrients to these responses.Anesthetized C57BL/6J female mice were orally gavaged with 1) a mixed meal (0.285kcal; glucose, whey protein and peanut oil; 60/20/20% kcal) versus an isocaloric glucose load (0.285kcal), and 2) a mixed meal (0.285kcal) versus glucose, whey protein or peanut oil administered individually in their mixed meal caloric quantity, i.e., 0.171, 0.055 and 0.055kcal, respectively. Plasma was analyzed for glucose, insulin and intact GLP-1 before and during oral challenges.Plasma glucose was lower after mixed meal versus after isocaloric glucose ingestion. In spite of this, the peak insulin response (P=0.02), the peak intact GLP-1 levels (P=0.006) and the estimated β-cell function (P=0.005) were higher. Furthermore, the peak insulin (P=0.004) and intact GLP-1 (P=0.006) levels were higher after mixed meal ingestion than the sum of responses to individual macronutrients.Compared to glucose alone, we conclude that there is a marked early insulin response to mixed meal ingestion, which emanates from a synergistic, rather than an additive, effect of the individual macronutrients in the mixed meal and is in part likely caused by increased levels of GLP-1.

Ethnic differences in glucose disposal, hepatic insulin sensitivity, and endogenous glucose production among African American and European American women

Intravenous glucose tolerance tests have demonstrated lower whole-body insulin sensitivity (SI) among African Americans (AA) compared with European Americans (EA). Whole-body SI represents both insulin-stimulated glucose disposal, primarily by skeletal muscle, and insulin's suppression of endogenous glucose production (EGP) by liver. A mathematical model was recently introduced that allows for distinction between disposal and hepatic SI. The purpose of this study was to examine specific indexes of SI among AA and EA women to determine whether lower whole-body SI in AA may be attributed to insulin action at muscle, liver, or both. Participants were 53 nondiabetic, premenopausal AA and EA women. Profiles of EGP and indexes of Disposal SI and Hepatic SI were calculated by mathematical modeling and incorporation of a stable isotope tracer ([6,6-2H2]glucose) into the intravenous glucose tolerance test. Body composition was assessed by dual-energy x-ray absorptiometry. After adjustment for percentage fat, both Disposal SI and Hepatic SI were lower among AA (P = .009 for both). Time profiles for serum insulin and EGP revealed higher peak insulin response and corresponding lower EGP among AA women compared with EA. Indexes from a recently introduced mathematical model suggest that lower whole-body SI among nondiabetic AA women is due to both hepatic and peripheral components. Despite lower Hepatic SI, AA displayed lower EGP, resulting from higher postchallenge insulin levels. Future research is needed to determine the physiological basis of lower insulin sensitivity among AA and its implications for type 2 diabetes mellitus risk.

Postprandial hyperglycemia and insulin response are affected by sea buckthorn (Hippophaë rhamnoides ssp. turkestanica) berry and its ethanol-soluble metabolites

Repeated postprandial hyperglycemia and subsequent mild, late hypoglycemia as well as high postprandial insulin response lead to metabolic events that may eventually develop into type 2 diabetes. The aim of this study was to assess how sea buckthorn berries as well as two sea buckthorn extraction residues modulate the postprandial metabolism after a high-glucose meal. Ten healthy normal-weight male volunteers consumed four study breakfasts, one control (A) and three sea buckthorn meals on four distinct study days. All the meals contained yoghurt and glucose (50 g). The sea buckthorn ingredients used were dried and crushed whole berries (meal B1), supercritical fluid (SF)-carbon dioxide (CO(2))-extracted oil-free berries (meal B2) or ethanol-extracted SF-CO(2)-extraction residue (meal B3). Blood samples for glucose, insulin and tumor necrosis factor-α analyses were collected before and during the 6-h study period. Meal B1 suppressed the postprandial peak insulin response when compared with meal A (Δconcentration of 30-min peak value--21.8 mU/l, P=0.039), and stabilized postprandial hyperglycemia and subsequent hypoglycemia (Δconcentration of 30-min peak value--120-min value -30.4 mU/l, P=0.036). Furthermore, meal B2 resulted in a more stable insulin response than the control meal (Δconcentration of 30-min peak value--120-min value -25.9 mU/l, P=0.037). Removal of the CO(2)-soluble oil component from the berries did not show a significant change in the studied postprandial effects of the berries. The EtOH soluble components, again showed advantageous properties in both insulin and glucose responses.

Reduced glycaemic and insulinaemic responses following isomaltulose ingestion: implications for postprandial substrate use

The impact of slow digestible sources of dietary carbohydrate in reducing the risk of developing obesity and related metabolic disorders is unclear. The aim of the present study was to compare the postprandial metabolic response to the ingestion of sucrose v. isomaltulose. We hypothesised that the reduced digestion and absorption rate of isomaltulose would result in lower glycaemic and insulinaemic responses when compared with the ingestion of sucrose, leading to greater postprandial fat oxidation rates. In a randomised, single-blind, cross-over study, ten overweight subjects ingested two different carbohydrate drinks (sucrose and isomaltulose, 75 g carbohydrate equivalents) following an overnight fast (08.40 hours) and with a standardised meal (12.30 hours, 25 % of total energy content was provided as either a sucrose or isomaltulose drink). Blood samples were taken before ingestion and every 30 min thereafter for a period of 3 h, substrate use was assessed by indirect calorimetry and breath samples were collected. Ingestion of carbohydrates with a mixed meal resulted in a lower peak glucose and insulin response and a lower change in area under the curve (DeltaAUC) following isomaltulose when compared with sucrose. Together with the lower glucose and insulin responses, postprandial fat oxidation rates were higher (14 %) with isomaltulose when compared with sucrose when ingested with a mixed meal (P = 0.02). The attenuated rise in glucose and insulin concentrations following isomaltulose results in reduced inhibition of postprandial fat oxidation. The metabolic response to isomaltulose co-ingestion suggests that this may represent an effective nutritional strategy to counteract overweight-induced metabolic disturbances.

Reduced glycaemic and insulinaemic responses following trehalose ingestion: implications for postprandial substrate use

The proposed impact of slowly digestible sources of dietary carbohydrate in reducing the risk of developing obesity and related metabolic disorders remains unclear. The aim of the present study was to compare the postprandial metabolic response to the ingestion of glucose v. trehalose. We hypothesised that the reduced digestion and absorption rate of trehalose is accompanied by an attenuated glycaemic and insulinaemic response, leading to a less inhibited postprandial fat oxidation rate. In a randomised, single-blind, cross-over study, ten overweight subjects ingested two carbohydrate drinks (75 g carbohydrate equivalents of trehalose or glucose) following an overnight fast (08.40 hours) and together with a standardised mixed meal (12.30 hours; 25 % total energy content was provided as either glucose or trehalose). Blood samples were collected before ingestion and every 30 min thereafter for a period of 3 h; substrate use was assessed by indirect calorimetry and expired breath samples were collected. Ingestion of carbohydrates with a mixed meal resulted in a lower peak glucose response and a lower change in area under the curve (DeltaAUC) following trehalose when compared with glucose. Differences in peak insulin response and DeltaAUC were observed with trehalose when compared with glucose during the morning and afternoon. These differences were accompanied with a reduced carbohydrate oxidation after trehalose when ingested as a drink, whilst no significant differences in fat oxidation between drink were observed.

Influence of BMI and Gender on Postprandial Hormone Responses

Influences of gender and body weight on the hormonal response to eating are not well understood. This study was conducted to determine a convenient time-point to evaluate peak postprandial hormone responses and to test the hypothesis that gender and BMI interact to produce differences in postprandial secretion of selected humoral markers implicated in hunger and satiety. Fasting blood glucose, insulin, leptin, ghrelin, glucagon-like peptide-1, and glucagon were measured in normal-weight (20 <or= BMI < 25 kg/m2) men (n = 10) and women (n = 9) and obese (BMI >or= 30 kg/m2) men (n = 9) and women (n = 11). A standard liquid meal was consumed, and humoral measurements were repeated every 10 minutes for 1 hour. Data were analyzed using repeated measures ANOVA with BMI and gender as main effects. Obese subjects had delayed peak insulin responses (p = 0.004), whereas obese men had a delayed nadir ghrelin response (p = 0.05). Obese subjects had higher and more sustained postprandial glucose (p = 0.02), and greater fasting (p = 0.0004) and postprandial insulin (p = 0.0001). Ghrelin decreased after the meal (p = 0.003); the percent change from fasting tended to be reduced in obese subjects (p = 0.07). Men had greater fasting (p = 0.02) and postprandial (p = 0.03) glucagon and a subtle postprandial decline in plasma leptin (p = 0.01). Peak hormone responses occurred 20 to 40 minutes after eating. Measurements made during this interval may be useful in evaluating postprandial response magnitude. Peak/nadir responses and time courses of postprandial responses are influenced by gender and BMI. Nutritional studies need to account for variability introduced by these factors.

Extract of Salacia oblonga lowers acute glycemia in patients with type 2 diabetes2–

Background: Two previous studies tested the efficacy of Salacia oblonga extract in healthy adults.Objective: This study evaluated the effect of an herbal extract of Salacia oblonga on postprandial glycemia and insulinemia in patients with type 2 diabetes after ingestion of a high-carbohydrate meal.Design: Sixty-six patients with diabetes were studied in this randomized, double-blinded crossover study. In a fasted state, subjects consumed 1 of the following 3 meals: a standard liquid control meal, a control meal + 240 mg Salacia oblonga extract, and a control meal + 480 mg Salacia oblonga extract. Serum glucose and insulin samples were measured at baseline and at postprandial intervals up to 180 min.Results: Both doses of the Salacia extract significantly lowered the postprandial positive area under the glucose curve (14% for the 240 mg extract and 22% for the 480 mg extract) and the adjusted peak glucose response (19% for the lower dose and 27% for the higher dose of extract) to the control meal. In addition, both doses of the herbal extract significantly decreased the postprandial insulin response, lowering both the positive area under the insulin curve and the adjusted peak insulin response (14% and 9%, respectively, for the 240 mg extract; 19% and 12%, respectively, for the 480 mg extract) in comparison with the control meal.Conclusions: The extract of Salacia oblonga lowers acute glycemia and insulinemia in persons with type 2 diabetes after a high-carbohydrate meal. The results from this study suggest that Salacia may be beneficial to this population for postprandial glucose control.

Almonds decrease postprandial glycemia, insulinemia, and oxidative damage in healthy individuals.

Strategies that decrease postprandial glucose excursions, including digestive enzyme inhibition, and low glycemic index diets result in lower diabetes incidence and coronary heart disease (CHD) risk, possibly through lower postprandial oxidative damage to lipids and proteins. We therefore assessed the effect of decreasing postprandial glucose excursions on measures of oxidative damage. Fifteen healthy subjects ate 2 bread control meals and 3 test meals: almonds and bread; parboiled rice; and instant mashed potatoes, balanced in carbohydrate, fat, and protein, using butter and cheese. We obtained blood samples at baseline and for 4 h postprandially. Glycemic indices for the rice (38 +/- 6) and almond meals (55 +/- 7) were less than for the potato meal (94 +/- 11) (P < 0.003), as were the postprandial areas under the insulin concentration time curve (P < 0.001). No postmeal treatment differences were seen in total antioxidant capacity. However, the serum protein thiol concentration increased following the almond meal (15 +/- 14 mmol/L), indicating less oxidative protein damage, and decreased after the control bread, rice, and potato meals (-10 +/- 8 mmol/L), when data from these 3 meals were pooled (P = 0.021). The change in protein thiols was also negatively related to the postprandial incremental peak glucose (r = -0.29, n = 60 observations, P = 0.026) and peak insulin responses (r = -0.26, n = 60 observations, P = 0.046). Therefore, lowering postprandial glucose excursions may decrease the risk of oxidative damage to proteins. Almonds are likely to lower this risk by decreasing the glycemic excursion and by providing antioxidants. These actions may relate to mechanisms by which nuts are associated with a decreased risk of CHD.

Impact of Steatosis on Insulin Secretion in Chronic Hepatitis C Patients

Liver steatosis is frequently observed in patients with chronic hepatitis C (CHC) and is an identified risk factor for progression of liver fibrosis. This study aimed to evaluate the relationship between steatosis and host/viral factors, and the correlation between steatosis and insulin secretion in CHC patients with normal glucose tolerance (NGT). A total of 212 CHC patients were enrolled in this study. Insulin resistance and insulin secretion were determined in response to oral loading of 75 g glucose. Liver fibrosis and steatosis were quantified by the image analysis. Of the 212 CHC patients, 165 (78%) had steatosis, mostly of a mild degree. Multiple ordinal regression analysis revealed body mass index (BMI) (P= 0.011) as the main factor associated with severe steatosis. Of the 212 CHC patients, 148 (61%) showed NGT, and the serum insulin response to oral glucose loading in these NGT patients with steatosis was significantly different from that in patients with NGT but no steatosis. The peak insulin response occurred at 60 min in cases of mild steatosis, and at 90 min in patients with moderate or severe steatosis. The insulin level at 120 min in patients with severe steatosis was higher than that in those without steatosis. The total area under the response curve of insulin during OGTT in the patients with steatosis is higher than that in those without steatosis. Exaggerated insulin secretion was observed even in CHC patients with mild steatosis and NGT, suggesting the presence of insulin resistance. Exaggerated insulin secretion may accelerate the progression of liver fibrosis in CHC patients.