Differences In Insulin Responses Research Articles

Gluten-free diet intervention reduces thiamine intake in two weeks, increases glycaemic response and decreases body weight in four weeks, with no long term nutritional deficiencies

This research investigated the effects of gluten free diet (GFD) on nutritional intake, glycaemic and insulin response. In a cross-sectional study, participants who consumed gluten-containing diet (GCD; n = 11) and GFD (n = 11) completed a food diary, blood glucose and insulin measurements. In a pre-post intervention study (n = 11), glycaemic and insulin responses were tested before and after four weeks of a GFD. Food intake was recorded before and after two weeks. No significant differences in nutrient intake, glycaemic or insulin responses were found in the cross-sectional study. In the intervention study, there was a significant reduction in body weight (p = .007) and body mass index (BMI) (p = .004) after four weeks and lower thiamine intake (p = .021) after two weeks of GFD. Glycaemic response was significantly higher (p < .05) following GFD with no differences in insulin response. These differences were not evident if GFD was followed for a longer period, possibly due to improved food choices.

Glucagon-like peptide-1 and beta cell glucose sensitivity - a glucose ramp study in mice

The incretin glucagon-like peptide-1 (GLP-1) is a gut hormone but also locally produced in pancreatic islets. We evaluated effects of GLP-1 on the insulin response to a gradual increase in glucose in mice within physiological levels. We initially developed a glucose ramp technique in mice. Glucose levels were slowly increased by 0.2 mmol/l/min for 40 min under control conditions, during intravenous infusion of GLP-1 and in GLP-1 receptor knockout mice. In control mice, glucose levels increased from 8.5 ± 0.3 to 16.1 ± 0.3 mmol/l over the 40 min, i.e., by 0.22 ± 0.01 mmol/l/min. This resulted in a slow increase in insulin levels by 96 ± 38 pmol/l from the baseline of 319 ± 53 pmol/l. GLP-1 at 0.5 nmol/kg as bolus plus 0.3 nmol/kg/min over 40 min progressively increased this insulin response by 100-fold, to 9.5 ± 0.2 nmol/l (P < 0.001). Higher doses of GLP-1 enhanced the insulin response similarly (1.0 or 3.0 nmol/kg bolus followed by 0.4 or 1.2 nmol/kg/min), whereas a lower dose (0.3 nmol/kg bolus plus 0.15 nmol/kg/min) had no significant effect compared to controls. Moreover, there was no significant difference in insulin responses between controls and GLP-1 receptor knockout mice. Since the increase in glucose levels were standardized, there was no significant difference in glucose levels between the experimental groups. We conclude that the glucose ramp technique is a tool for studies on insulin responses to slow changes in circulating glucose levels in mice. We also conclude that GLP-1 is extraordinarily potent in enhancing the insulin response to a slow increase in glucose levels.

Regional Variations of Insulin Secretion and Insulin Sensitivity in Japanese Participants With Normal Glucose Tolerance.

Purpose: Regional differences in dietary patterns in Asian countries might affect the balance of insulin response and sensitivity. However, this notion is yet to be validated. To clarify the regional differences in the insulin response and sensitivity and their relationship to nutrients, we compared the insulin secretory response during an oral glucose tolerance test in Japanese participants.Methods: This observational retrospective cohort study analyzed the data from participants with normal glucose tolerance (NGT) from four distinct areas of Japan with regard to the food environment: Fukushima, Nagano, Tokushima, and Okinawa based on data available in the Japanese National Health Insurance database.Results: Although the glucose levels were comparable among the four regions, the insulin responses were significantly different among the regions. This difference was observed even within the same BMI category. The plot between the insulin sensitivity index (Matsuda index) and insulinAUC/glucoseAUC or the insulinogenic index showed hyperbolic relationships with variations in regions. The indices of insulin secretion correlated positively with fat intake and negatively with the intake of fish, carbohydrate calories, and dietary fiber.Conclusions: We found that significant regional differences in insulin response and insulin sensitivity in Japanese participants and that nutritional factors may be linked to these differences independently of body size/adiposity. Insulin response and insulin sensitivity can vary among adult individuals, even within the same race and the same country, and are likely affected by environmental/lifestyle factors as well as genetic traits.

Enrichment of bread with beta-glucans or resistant starch induces similar glucose, insulin and appetite hormone responses in healthy adults.

β-Glucans (βG) and resistant starch (RS) are known for their effects on the improvement of glucose tolerance and enhancement of insulin sensitivity. Enrichment of bread with βG or RS was performed to examine potential postprandial benefits regarding gastrointestinal hormone responses. Ten healthy normoglycaemic adults participated in the study and were provided with either a glucose solution (reference food, GS) or bread enriched with β-glucans (βGB) (3.6g/30g available CHO) or bread enriched with resistant starch (RSB) (15% of total starch), with 1-week intervals in amounts that yielded 50g of available carbohydrates. Venous blood samples were collected before consumption and at 15, 30, 45, 60, 90, 120 and 180min postprandially. Glucose, insulin, ghrelin, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) responses as well as glycaemic index (GI) and subjective appetite ratings were evaluated. Ingestion of βGB and RSB elicited lower incremental area under the curve (iAUC) for glycaemic response compared to GS (P < 0.05). Both breads demonstrated a low GI (βGB: 48, RSB: 40). There were no significant differences in insulin response, ghrelin, GLP-1 or PYY between the two breads. A significantly lower desire to eat and higher fullness were detected 15min after βGB and RSB consumption and until 180min (P < 0.05 compared to GS). Enrichment of bread with either βG or RS produced a low GI product but the two breads were not significantly different in relation to insulin, ghrelin, GLP-1 and PYY responses. The development of bread products which cause improved metabolic effects is of great importance for the promotion of public health.

Glycaemic response at night is improved after eating a high protein meal compared with a standard meal: A cross-over study

Eating at night, compared to day-time, results in a relative hyperglycaemia contributing to an increased risk of Type 2 diabetes for those who habitually eat at night, such as shift workers. Meal choice at night can adversely impact postprandial glycaemia. Meals high in protein have the capacity to favourably reduce night time perturbations in glucose. The aim of this study was to examine if a high protein meal attenuates postprandial glucose at night, compared with a standard protein meal. In a 2×2 factor cross over design, healthy adults completed four acute meal challenges. Test meals were consumed at 8am and 8pm on separate occasions; a high protein (HP) meal (41% of energy from protein, 29% from carbohydrates) or isocaloric standard meal (15% from protein, 46% from carbohydrate). Bloods were sampled at fasting and for three hours postprandially and incremental area under the curve (iAUC) determined using the trapezoid rule. Freidman's test was conducted prior to post hoc Wilcoxon sign test, and significance set at p<0.0083 after Bonferroni correction. Plasma glucose median (IQR) iAUC after the HP meal was similar to the standard meal when consumed in the morning (12.9 (19.9) vs. 36.4 (99.6)mmol/L.3h, p=0.028). The HP meal elicited a significantly lower glucose iAUC (59.6 (117.0)mmol/L.3h) compared to the standard meal (208.8 (154.1)mmol/L.3h) when consumed at night (p=0.005). No significant differences in insulin responses were found between test meals, at either time of day (p=0.100). A HP meal is effective in attenuating the postprandial glucose excursion observed with night eating by 71.4%, compared to a meal with a macronutrient composition within dietary guidelines. If eating at night, reducing the carbohydrate content of a meal, and replacing this with protein, can result in a more favourable postprandial metabolic response. Trial ID number: ACTRN12617000294358, Website of trial registry: http://www.anzctr.org.au/.

Effects of insulin and pathway inhibitors on the PI3K-Akt-mTOR phosphorylation profile in acute myeloid leukemia cells

The phosphatidylinositol 3-kinase (PI3K)-Akt-mechanistic target of rapamycin (mTOR) pathway is constitutively activated in human acute myeloid leukemia (AML) cells and is regarded as a possible therapeutic target. Insulin is an agonist of this pathway and a growth factor for AML cells. We characterized the effect of insulin on the phosphorylation of 10 mediators in the main track of the PI3K-Akt-mTOR pathway in AML cells from 76 consecutive patients. The overall results showed that insulin significantly increased the phosphorylation of all investigated mediators. However, insulin effects on the pathway activation profile varied among patients, and increased phosphorylation in all mediators was observed only in a minority of patients; in other patients, insulin had divergent effects. Global gene expression profiling and proteomic/phosphoproteomic comparisons suggested that AML cells from these two patient subsets differed with regard to AML cell differentiation, transcriptional regulation, RNA metabolism, and cellular metabolism. Strong insulin-induced phosphorylation was associated with weakened antiproliferative effects of metabolic inhibitors. PI3K, Akt, and mTOR inhibitors also caused divergent effects on the overall pathway phosphorylation profile in the presence of insulin, although PI3K and Akt inhibition caused a general reduction in Akt pT308 and 4EBP1 pT36/pT45 phosphorylation. For Akt inhibition, the phosphorylation of upstream mediators was generally increased or unaltered. In contrast, mTOR inhibition reduced mTOR pS2448 and S6 pS244 phosphorylation but increased Akt pT308 phosphorylation. In conclusion, the effects of both insulin and PI3K-Akt-mTOR inhibitors differ between AML patient subsets, and differences in insulin responsiveness are associated with differential susceptibility to metabolic targeting.

Postprandial Glycaemic and Insulinaemic Responses after Consumption of Activated Wheat and Triticale Grain Flakes.

Increasing evidence shows that whole grain consumption is protective against metabolic disorders. Protective bioactive substances of whole grains include fibre and antioxidants. Activation of grains can increase the amount of phenolic compounds and their bioavailability, but there is little evidence about their effect on glycaemic and insulinemic responses. Therefore, the aim of this study was to investigate glycaemic and insulinemic responses after consumption of flakes made from activated wheat and activated triticale grains. Eighteen healthy subjects (7 men and 11 women) were given activated wheat or activated triticale flakes. As a reference, a standard glucose solution was used. Plasma glucose and serum insulin were measured during 120 minutes. Both, activated wheat and activated triticale flakes, show improved glycaemic profile, inducing a lower and more stable glycaemic response. However, statistically significant differences in insulin response were found only in the group who have taken activated triticale flakes and not in the group who have taken activated wheat flakes. Activated triticale flakes induced lower insulin response in all postprandial phases and a more stable concentration of insulin. Thus, activated triticale flakes could be beneficial for the prevention and treatment of metabolic disorders.

Very high-protein and low-carbohydrate enteral nutrition formula and plasma glucose control in adults with type 2 diabetes mellitus: a randomized crossover trial

Background and objectivesStandard enteral nutrition (EN) formulas can worsen hyperglycemia in diabetic patients. We hypothesized that altering the proportion of macronutrients in a formula; increasing protein while decreasing carbohydrate concentrations would improve glycemic response. The objective of this study was to demonstrate that an EN formula containing a very high concentration of protein (in the form of whey peptides) and low concentration of carbohydrate provide better control of postprandial blood glucose relative to a very high-protein/higher-carbohydrate formula.Subjects and methodsThis was a randomized crossover clinical trial of 12 ambulatory adult subjects with type 2 diabetes. The primary outcome was glycemic response following a bolus of isocaloric amounts of two EN formulas; the secondary outcome was insulin response. Subjects were randomized to the experimental or the control formula, on two separate days, 5–7 days apart.ResultsMean blood glucose concentrations at 10–180 min post-infusion and mean area under the curve for glucose over 240 min post-infusion were significantly lower with the experimental formula than with the control formula (71.99 ± 595.18 and 452.62 ± 351.38, respectively; p = 0.025). There were no significant differences in the mean insulin concentrations over time, insulinogenic indices, and first-phase insulin measurements.ConclusionsAn EN formula containing high-protein and low-carbohydrate loads can significantly improve glucose control in subjects with type 2 diabetes in ambulatory settings as evidenced by observed improved glucose control without significant difference in insulin response.

Assessment of glucose regulation in pregnancy after gastric bypass surgery

Aims/hypothesisRoux-en-Y gastric bypass (RYGB) surgery is characterised by glycaemic variability. Prospective studies of glucose metabolism in pregnancy after RYGB are not available, therefore this study aimed to evaluate physiological alterations in glucose metabolism in pregnancy following RYGB.MethodsSixty-three pregnant women (25 who underwent RYGB, 19 non-operated obese control women and 19 normal weight control women) were included. Frequently sampled 3 h OGTTs and 1 h IVGTTs were performed between 24 and 28 weeks of gestation and, in a subgroup, were repeated at 3–6 months after delivery.ResultsWe observed major alterations in glucose kinetics during the OGTT, including an early increase in plasma glucose followed by hypoglycaemia in 90% of women who had previously undergone RYGB. The higher degree of glycaemic variability in this group was accompanied by increased insulin, C-peptide and glucagon concentrations after oral glucose load, whereas no differences in insulin response were observed after parenteral glucose administration (RYGB vs normal weight). IVGTT data suggested improved insulin sensitivity (mean difference 0.226 × 10−4 min−1 [pmol/l]−1 [95% CI 0.104, 0.348]; p < 0.001) and disposition index in pregnancies after RYGB when compared with obese control women. However, subtle alterations in insulin action and beta cell function were still observed when comparing women who had undergone RYGB with the normal-weight control group. Moreover, we observed that fetal growth was associated with maternal glucose nadir levels and insulin secretion in offspring of those who had previously undergone RYGB.Conclusions/interpretationPregnancies after RYGB are affected by altered postprandial glucose, insulin and C-peptide dynamics. Insulin sensitivity is improved by RYGB, although subtle alterations in beta cell function are observed. Longitudinal studies are needed to assess potential consequences for fetal development and pregnancy outcomes.

The effect of breakfast type and frequency of consumption on glycemic response in overweight/obese late adolescent girls.

The primary aim was to examine the daily glycemic response to normal-protein (NP) vs higher-protein (HP) breakfasts in overweight adolescents who habitually skip breakfast (H-BS). The secondary aim examined whether the glycemic response to these meals differed in H-BS vs habitual breakfast consumers (H-BC). Thirty-five girls (age: 19 ± 1 year; body mass index: 28.4 ± 0.7 kg/m(2)) participated in the semi-randomized crossover-design study. The participants were grouped according to habitual breakfast frequency. H-BS (n = 20) continued to skip breakfast (BS) or consumed a NP (12 g protein) or HP (32 g protein) breakfast for 3 days, whereas the H-BC (n = 15) completed the NP and HP breakfast conditions for 3 days. On day 4 of each pattern, an 8 h testing day was completed. The respective breakfast and a standard lunch meal were provided, and plasma was collected to assess morning, afternoon, and total glucose and insulin area under the curves (AUC). In H-BS, the addition of a HP breakfast increased total glucose AUC vs BS (P < 0.05), whereas NP breakfast increased total insulin AUC vs BS (P < 0.05). In H-BC, the HP breakfast reduced morning, afternoon and total glucose AUCs vs NP (all, P < 0.05). No differences in insulin were detected. When comparing the HP-NP differential glycemic responses between groups, H-BS experienced greater afternoon and total glucose AUCs following HP vs NP breakfasts (both, P<0.05). No differences in insulin responses were observed between groups. Novel differences in the glucose response to HP vs NP breakfasts were observed and were influenced by the frequency of habitual breakfast consumption in overweight adolescents.

Compensatory responses to insulin resistance in obese African‐American and Latina girls

Insulin responses to oral and intravenous glucose markedly differ by ethnicity. This study examined whether ethnic differences in pancreatic insulin secretion, hepatic insulin extraction and clearance explain these disparate findings in 35 obese African-American and 41 Latina girls (Tanner Stages: IV-V; ages: 14-18; body mass index percentile: 85.9-99.8%). Pancreatic insulin secretion, hepatic insulin extraction and clearance were estimated by C-peptide and insulin modeling during an oral glucose tolerance test. Insulin sensitivity (SI), acute insulin response to glucose (AIRG ) and disposition index were derived from a frequently sampled intravenous glucose tolerance test. Compared to Latinas, obese African-American adolescents had lower pancreatic insulin secretion (21.3%; P < 0.01), glucose incremental area under the curve (IAUC) (41.7%, P = 0.02), C-peptide IAUC (25.1%, P < 0.01) and SI (33.7%; P < 0.01). There were no ethnic differences in hepatic insulin extraction and clearance (P's > 0.05). Compensatory mechanisms to insulin resistance do not appear to explain the ethnic differences in insulin responses to oral and intravenous glucose in obese African-American and Latina girls.

Food intake, postprandial glucose, insulin and subjective satiety responses to three different bread-based test meals

The effect of bread consumption on overall food intake is poorly understood. The aim of this study was to measure postprandial food intake after a set breakfast containing three different breads. Ten males and 10 females aged 20.1–44.8 years, BMI 18.4–24.8 kg/m 2, consumed two slices of White Bread, Bürgen ® Wholemeal and Seeds Bread or Lupin Bread (all 1300 kJ) with 10 g margarine and 30 g strawberry jam. Fullness and hunger responses and were measured before and during the test breakfasts. Glucose and insulin responses (incremental area under each two-hour curve (iAUC)) were calculated. Food intake was measured and energy and nutrient intake determined at a buffet meal two hours later. Subjects consumed significantly less energy after the Bürgen ® Bread meal compared to the White Bread meal (2548 ± 218 vs. 3040 ± 328 kJ, Bürgen ® Bread vs. White Bread, P < 0.05). There were higher fullness responses for the Lupin Bread ( P < 0.01), and the Bürgen ® Bread ( P < 0.05) compared with the White Bread. Lupin Bread and Bürgen ® Bread produced smaller postprandial glucose responses (79 ± 7, 74 ± 4, 120 ± 10 mmol/L min iAUC, Lupin, Bürgen ® and White Bread respectively, P < 0.01). Differences in insulin responses were also observed (6145 ± 1048, 6471 ± 976, 9674 ± 1431 pmol/L min iAUC, Lupin, Bürgen ® and White Bread respectively, P < 0.01). Equal-energy portions of three different commercially available breads differed in their short-term satiation capacity. Further studies are needed to demonstrate any potential benefit for weight management.

Periparturient effects of feeding a low dietary cation-anion difference diet on acid-base, calcium, and phosphorus homeostasis and on intravenous glucose tolerance test in high-producing dairy cows

Feeding rations with low dietary cation-anion difference (DCAD) to dairy cows during late gestation is a common strategy to prevent periparturient hypocalcemia. Although the efficacy of low-DCAD rations in reducing the incidence of clinical hypocalcemia is well documented, potentially deleterious effects have not been explored in detail. The objective of the study presented here was to determine the effect of fully compensated metabolic acidosis on calcium and phosphorus homeostasis, insulin responsiveness, and insulin sensitivity as well as on protein metabolism. Twenty multiparous Holstein-Friesian dairy cows were assigned to 1 of 2 treatment groups and fed a low-DCAD ration (DCAD = −9 mEq/100g, group L) or a control ration (DCAD = +11 mEq/100g, group C) for the last 3 wk before the expected calving date. Blood and urine samples were obtained periodically between 14 d before to 14 d after calving. Intravenous glucose tolerance tests and 24-h volumetric urine collection were conducted before calving as well as 7 and 14 d postpartum. Cows fed the low-DCAD ration had lower urine pH and higher net acid excretion, but unchanged blood pH and bicarbonate concentration before calving. Protein-corrected plasma Ca concentration 1 d postpartum was higher in cows on the low-DCAD diet when compared with control animals. Urinary Ca and P excretion was positively associated with urine net acid excretion and negatively associated with urine pH. Whereas metabolic acidosis resulted in a 6-fold increase in urinary Ca excretion, the effect on renal P excretion was negligible. A more pronounced decline of plasma protein and globulin concentration in the periparturient period was observed in cows on the low-DCAD diets resulting in significantly lower total protein and globulin concentrations after calving in cows on low-DCAD diets. Intravenous glucose tolerance tests conducted before and after calving did not reveal group differences in insulin response or insulin sensitivity. Our results indicate that fully compensated metabolic acidosis increased the Ca flux resulting in increased urinary calcium excretion before calving and increased plasma Ca concentration on the day after calving, whereas the effect on P homeostasis was unlikely to be clinically relevant. The clinical relevance of the effect of metabolic acidosis on the plasma protein and globulin concentration is unclear but warrants further investigation.

A novel wheat variety with elevated content of amylose increases resistant starch formation and may beneficially influence glycaemia in healthy subjects

BackgroundPrevious studies indicate that elevated amylose content in products from rice, corn, and barley induce lower postprandial glycaemic responses and higher levels of resistant starch (RS). Consumption of slowly digestible carbohydrates and RS has been associated with health benefits such as decreased risk of diabetes and cardiovascular disease.ObjectiveTo evaluate the postprandial glucose and insulin responses in vivo to bread products based on a novel wheat genotype with elevated amylose content (38%).DesignBread was baked from a unique wheat genotype with elevated amylose content, using baking conditions known to promote amylose retrogradation. Included test products were bread based on whole grain wheat with elevated amylose content (EAW), EAW with added lactic acid (EAW-la), and ordinary whole grain wheat bread (WGW). All test breads were baked at pumpernickel conditions (20 hours, 120°C). A conventionally baked white wheat bread (REF) was used as reference. Resistant starch (RS) content was measured in vitro and postprandial glucose and insulin responses were tested in 14 healthy subjects.ResultsThe results showed a significantly higher RS content (on total starch basis) in breads based on EAW than in WGW (p<0.001). Lactic acid further increased RS (p<0.001) compared with both WGW and EAW. Breads baked with EAW induced lower postprandial glucose response than REF during the first 120 min (p<0.05), but there were no significant differences in insulin responses. Increased RS content per test portion was correlated to a reduced glycaemic index (GI) (r= − 0.571, p<0.001).ConclusionsThis study indicates that wheat with elevated amylose content may be preferable to other wheat genotypes considering RS formation. Further research is needed to test the hypothesis that bread with elevated amylose content can improve postprandial glycaemic response.

Influence of the glycemic load (GL) on subjective and objective measures of sleep quality in insomnia

Evidence in healthy sleepers suggests the glycemic index (GI) can mediate changes in sleep onset latency, given the availability of tryptophan to the brain (i.e. TRP/LNAA ratio) is increased after high GI carbohydrate-only food. However, these meals have limited clinical application given the high glycemic load (GL) and insulin responses. Therefore, we investigated the efficacy of a mixed macronutrient high GI (MHGI) compared to an isoenergetic (∼1915 kJ) low GI (MLGI) meal taken three hours prior to habitual bedtime to improve sleep quality in participants meeting research diagnostic criteria for insomnia. Four men and four women (n=8) were randomized to the MHGI or MLGI meal for two consecutive nights. Blood samples were taken prior to the meal, and 60, 120, 180 min after eating. Subjective (sleep diary) and objective (polysomnography, PSG) sleep was also measured each night. The individual 10cm visual analogue scales indicate that meal palatability was identical for both meals; which were of good taste (average 7.8cm); meal satiety was maintained until bedtime after the MHGI meal (&gt;5cm), whereas after the MLGI meal satiety ratings in men were low (&lt;5cm); and the average meal energetic load (kJ/kg) was greater for women (33.0 ± 4.1) than men (25.4 ± 3.8; p&lt;0.05). Postprandial measures indicate glucose was larger after the MHGI meal but there was no difference in insulin response; the peak percentage rise in plasma TRP/LNAA from baseline after the MHGI meal (17%) was substantially but only marginally different than the MLGI (8%) meal (p = 0.12); postprandial serotonin was unaltered. The participant group self-reported (5pt Likert scale) feeling more rested after the MHGI (2.8) compared to the MLGI meal (2.3; p&lt;0.05); also ratings were higher in women (3.0) than in men (2.6; p&lt;0.05). There were no differences in PSG sleep variables. This study demonstrates symptoms of insomnia are improved, especially in women, after a high GI mixed macronutrient meal. Given the present data, we suggest the possibility for a physiological threshold within the postprandial plasma TRP/LNAA response that must be surpassed in order to promote measurable changes to serotonin and PSG sleep. Further studies should evaluate the potential long-term risks and benefits of habitual mixed macronutrient high GI meals to improve sleep.

Effects of twin pregnancy and periconceptional undernutrition on maternal metabolism, fetal growth and glucose–insulin axis function in ovine pregnancy

Although twins have lower birthweights than singletons, they may not experience the increased disease risk in adulthood reportedly associated with low birthweight. In contrast, another periconceptional event, maternal undernutrition, does not reduce birthweight but does affect fetal and postnatal physiology in sheep. We therefore studied maternal and fetal metabolism, growth and glucose-insulin axis function in late gestation in twin and singleton sheep pregnancies, either undernourished from 60 days before until 30 days after conception or fed ad libitum. We found that twin-bearing ewes had decreased maternal food intake in late gestation and lower maternal and fetal plasma glucose and insulin levels. Twin fetuses had fewer everted placentomes, grew slower in late gestation, and had a greater insulin response to a glucose challenge, but lesser response to arginine. In contrast, periconceptional undernutrition led to increased maternal food intake and a more rapid fall in maternal glucose levels in response to fasting. Periconceptional undernutrition increased the number of everted placentomes, and abolished the difference in insulin responses to glucose between twins and singletons. Thus, the physiology of twin pregnancy is quite different from that of singleton pregnancy, and is probably determined by a combination of factors acting in both early and late gestation. The inconsistency of the relationships between low birthweight and postnatal disease risk of twins may lie in their very different fetal development. These data suggest that twin pregnancy may be another paradigm of developmental programming, and indicate that twins and singletons must be examined separately in any study of fetal or postnatal physiology.

Insulin-Like Factor 3: A New Circulating Hormone Related to Luteinizing Hormone-Dependent Ovarian Hyperandrogenism in the Polycystic Ovary Syndrome

Insulin-like factor 3 (INSL3), a circulating peptide hormone and a member of the relaxin-insulin family, is produced in the testicular Leydig cells and, to a lesser extent, in ovarian theca interna cells of antral follicles, the corpora lutea, and the ovarian stroma. Recent studies in rats suggest an important role for luteinizing hormone (LH) in stimulating gonadal expression of INSL3. Most women with polycystic ovary syndrome (PCOS) have a hyperplastic theca intema and cortical stroma and an increased number of small antral follicles. A majority-specially non-obese patients-have elevated circulating LH levels. This study estimated circulating levels of INSL3 by radioimmunoassay in 22 women with PCOS and normal body weight and 22 others who were overweight (body mass index [BMI] of 25-30 kg/m 2 ) or obese (BMI exceeding 30 kg/m 2 ). Each was matched for age and body weight with a non-PCOS control subject. Compared with control women, those with PCOS had greater insulin responses to oral glucose, higher androgen levels, and less frequent menstruation. Differences in androgen levels were most evident in normal-weight subjects, while differences in insulin responses to glucose were more evident in overweight/obese women. Baseline LH levels were highest in PCOS women of normal body weight. Serum levels of INSL3 were significantly higher in PCOS women than in control subjects, but only in those of normal body weight. In all women, serum INSL3 correlated positively with levels of total and free testosterone and with LH levels. In women with PCOS, concentrations of INSL3 were associated with greater responses of 170H-progesterone to buserelin, an index of ovarian hyperandrogenism. Levels of INSL3 also correlated positively with the number of ovarian follicles in women with PCOS. In contrast, women with PCOS exhibited no significant correlation between baseline LH levels and the number of follicles. These findings could be interpreted to mean that INSL3 is a circulating hormone related to LH-dependent ovarian hyperandrogenism in women with PCOS and normal body weight.

An Integrated Glucose‐Insulin Model to Describe Oral Glucose Tolerance Test Data in Type 2 Diabetics

An integrated model for the glucose-insulin system describing oral glucose tolerance test data was developed, extending on a previously introduced model for intravenous glucose provocations. Model extensions comprised the description of glucose absorption by a chain of transit compartments with a mean transit time of 35 minutes, a bioavailability of 80%, and a representation of the incretin effect, expressed as a direct effect of the glucose absorption rate on insulin secretion. The ability of the model to predict the incretin effect was assessed by simulating the observed difference in insulin response following an oral glucose tolerance test compared with an isoglycemic glucose infusion mimicking an oral glucose tolerance test profile. The extension of the integrated glucose-insulin model to gain information from oral glucose tolerance test data considerably expands its range of applications because the oral glucose tolerance test is one of the most common glucose challenge experiments for assessing the efficacy of hypoglycemic agents in clinical drug development.

Pinto bean, navy bean, and black-eyed pea consumption do not significantly lower the glycemic response to a high glycemic index treatment in normoglycemic adults

Abstract This study examined the effects of pinto bean, black-eyed pea, and navy bean consumed in 2 amounts, low dose (∼1/2 cup) and high dose (∼1 cup), on the glycemic response to a high glycemic index (GI) treatment (calculated glycemic index = 96) in insulin-sensitive adult men and women. In a randomized, crossover, placebo-controlled design, 12 participants consumed each of the low-dose treatments and 11 participants consumed each of the high-dose treatments in conjunction with a high-GI meal on different mornings, at least 7 days apart. Blood samples collected at time 0 (fasting) and at 30, 60, 90, and 120 minutes posttreatment were analyzed for glucose and insulin. Data were analyzed in 2 groups: low-dose (n = 12) and high-dose (n = 11) treatments. The low-dose treatments were also compared with the high-dose treatments (n = 11). There were no significant time-by-treatment interactions for any of the legume treatments at either the low-dose or high-dose amounts. No significant difference in insulin response, whole-body insulin sensitivity, or homeostasis model assessment for low-dose, high-dose, or low- vs high-dose treatments was found. When provided in the form of a spread, pinto bean, navy bean, or black-eyed pea intake as part of a treatment did not significantly reduce glycemic response to high-GI foods.

Impact of cereal fibre on glucose-regulating factors

Insoluble dietary fibre intake is associated, by unknown mechanisms, with a reduced risk of type 2 diabetes. We investigated whether a short-term dietary intervention with purified insoluble fibres influences acute and delayed responses of glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1. Fourteen healthy women with NGT were studied for 300 min on six to eight occasions. Subjects consumed three matched portions of control (C) or fibre-enriched bread (10.4-10.6 g/portion; wheat fibre [WF], oat fibre [OF], and, in a substudy [n=9], resistant starch [RS]) followed by control (C-C, C-WF, C-OF, C-RS) on subsequent days. Fibre enrichment accelerated the early insulin response (fibrextime interaction p=0.026 for WF, p<0.001 for OF, p=0.126 for RS; time of maximal concentration [T(max)], C 57.9+/-5.9, WF 49.3+/-2.5 [p=0.086], OF 46.1+/-2.9 [p=0.026], RS 46.7+/-5.8 min [p=0.029]). It was also associated with an earlier postprandial GIP response after OF (T(max), C 83.6+/-7.2, WF 70.7+/-6.0 [p=0.054], OF 64.3+/-6.9 [p=0.022], RS 60.0+/-5.0 [p>0.15]). Increased fibre intake for 24 h was further associated with a reduced postprandial glucose response on the following day subsequent to ingestion of a control meal (AUC(C-C) 4,140+/-401, AUC(C-WF) 2,850+/-331 [p=0.007], AUC(C-OF) 2,830+/-277 [p=0.011]), with no difference in maximal concentration and T(max) of glucose responses. No differences in insulin responses were observed 24 h after the fibre-enriched diets compared with control (p>0.15). Colonic fermentation was increased only on study days C-OF (p=0.017) and C-RS (p=0.016). The consumption of highly purified insoluble dietary fibres accelerated the acute GIP and insulin response and was further associated with enhanced postprandial carbohydrate handling the following day upon ingestion of a control meal.