Low Insulin Response Research Articles

Impaired insulin secretion increases the risk of Alzheimer disease

Subjects with diabetes are reported to have an increased risk of dementia and cognitive impairment. However, the underlying causes remain unknown. We investigated the longitudinal associations between midlife insulin secretion, glucose metabolism, and the subsequent development of Alzheimer disease (AD) and dementia. The population-based Uppsala Longitudinal Study of Adult Men started 1970 when the 2,322 participants were 50 years old. Investigation at baseline included determinations of acute insulin response and glucose tolerance using the IV glucose tolerance test and Homeostasis Model Assessment insulin resistance index. During a median follow up of 32 years, 102 participants were diagnosed with AD, 57 with vascular dementia, and 394 with any dementia or cognitive impairment. Associations were analyzed using Cox proportional hazard models. A low insulin response at baseline was associated with a higher cumulative risk of AD (hazard ratio for 1 SD decrease, 1.31; 95% CI, 1.10-1.56) also after adjustment for age, systolic blood pressure, body mass index, serum cholesterol, smoking, education level, and insulin resistance. This association was stronger in subjects without the APOE epsilon4 allele. Impaired glucose tolerance increased the risk of vascular dementia (hazard ratio for 1 SD decrease, 1.45; 95% CI, 1.05-2.00) but not AD. Impaired insulin secretion, glucose intolerance, and estimates of insulin resistance were all associated with higher risk of any dementia and cognitive impairment. In this longitudinal study, impaired acute insulin response at midlife was associated with an increased risk of Alzheimer disease (AD) up to 35 years later suggesting a causal link between insulin metabolism and the pathogenesis of AD.

Insulin Resistance and Progression to Type 1 Diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT)

The accelerator hypothesis proposes that type 1 and type 2 diabetes are both driven by insulin resistance (1), and its principle prediction is an inverse correlation between BMI and age at onset in children with type 1 diabetes. Bingley et al. (2) examined ENDIT data and found evidence for an inverse correlation only among those with advanced β-cell loss (low first-phase insulin response) (FPIR). They conclude that insulin …

Plasma proteome changes in subjects with Type 2 diabetes mellitus with a low or high early insulin response

Circulating proteins contribute to the pathogenesis of T2DM (Type 2 diabetes mellitus) in various ways. The aim of the present study was to investigate variations in plasma protein levels in subjects with T2DM and differences in beta-cell function, characterized by the EIR (early insulin response), and to compare these protein levels with those observed in individuals with NGT (normal glucose tolerance). Ten subjects with NGT+high EIR, ten with T2DM+high EIR, and ten with T2DM+low EIR were selected from the community-based ULSAM (Uppsala Longitudinal Study of Adult Men) cohort. Plasma protein profiling was performed using SELDI-TOF (surface-enhanced laser-desorption ionization-time-of-flight) MS. In total, nine plasma proteins differed between the three study groups (P<0.05, as determined by ANOVA). The levels of two forms of transthyretin, haemoglobin alpha-chain and haemoglobin beta-chain were decreased in plasma from subjects with T2DM compared with subjects with NGT, irrespective of the EIR of the subjects. Apolipoprotein H was decreased in plasma from individuals with T2DM+high EIR compared with subjects with NGT. Four additional unidentified plasma proteins also varied in different ways between the experimental groups. In conclusion, the proteins detected in the present study may be related to the development of beta-cell dysfunction.

EVALUATION OF GLUCOSE HOMEOSTASIS IN TRANSFUSION-DEPENDENT THALASSEMIC PATIENTS

Diabetes is an important problem encountered in thalassemic patients. The severity and type of glucose disturbances vary greatly in different studies. Also the pathogenesis seems to be complex; either insulin deficiency or insulin resistance may mediate the glucose disturbances. In a group of thalassemic patients glucose homeostasis was evaluated. Diabetes prevalence was 1.8%. Forty patients were investigated both with an oral glucose tolerance test and first-phase insulin response. Three patients had impaired fasting glucose, 1 patient had impaired glucose tolerance, and 2 patients had hyperinsulinism. Nineteen of 40 patients who were tested had low first-phase insulin response (47.5%) with below 10th centile. Age, BMI, height SDS, age at diagnosis, age at first blood transfusion, number of blood transfusions in a year, percentage of elevated liver enzyme, and hemoglobin and ferritin levels were not different between patients with low first-phase insulin response to patients with normal first-phase insulin response. Four patients are HCV infected, and only 1 of them had low first-phase insulin response. The study group showed a high rate of impairement in insulin secretion by first-phase insulin response to glucose overload, despite the low rate of insulin resistance. Defect of insulin secretion in thalassemic patients may develop earlier than insulin resistance, and then be accompanied by insulin resistance. Increasing insulin resistance with age and the occurrence of additional factors could lead to detoriation of glucose metabolism.

The Effects of Nonstructural Carbohydrate Content and Feeding Rate on Glucose and Insulin Response to Meal Feeding in Equine

The following research encompassed two experiments and involved feeding horses two isocaloric diets (diet A and diet B), with an approximate 50% difference in nonstructural carbohydrate (NSC) content. There were three main objectives: first, to test the hypothesis that feeding an approximately 50% lower NSC concentrate feed would cause a lower glucose and insulin response; second, to test the hypothesis that feeding meals equal in NSC content would create similar responses in glucose and insulin dynamics; and finally, to test the hypothesis that the time spent eating is correlated with glucose/insulin response. In experiment 1, in which diet A and diet B were fed at the same rate, the main finding was that feeding a meal lower in NSC resulted in a lower glucose and insulin response to the feed. In experiment 2, in which the effects of feeding diets A and B at a rate to provide 0.3 g/kg body weight (BW) NSC per meal were explored, the main finding was that, although glucose responses were similar, the meal containing more NSC/kg and fed at the lower rate resulted in a substantially lower insulin response. Consumption time also was found to be significantly different between treatments. In conclusion, a low NSC formulation and small meal size appear to be sensible recommendations for horses that may benefit from a low glucose and insulin response to feeding. In addition to NSC content, meal size, and nutrient:calorie ratio, nutrient requirements of the individual horse and the entire nutritional balance of the diet also should be addressed.

The effect of different protein hydrolysate/carbohydrate mixtures on postprandial glucagon and insulin responses in healthy subjects

To study the effect of four protein hydrolysates from vegetable (pea, gluten, rice and soy) and two protein hydrolysates from animal origin (whey and egg) on glucagon and insulin responses. Eight healthy normal-weight male subjects participated in this study. The study employed a repeated-measures design with Latin square randomization and single-blind trials. Protein hydrolysates used in this study (pea, rice, soy, gluten, whey and egg protein hydrolysate) consisted of 0.2 g hydrolysate per kg body weight (bw) and 0.2 g maltodextrin per kg bw and were compared to maltodextrin alone. Postprandial plasma glucose, glucagon, insulin and amino acids were determined over 2 h. All protein hydrolysates induced an enhanced insulin secretion compared to maltodextrin alone and a correspondingly low plasma glucose response. A significant difference was observed in area under the curve (AUC) for plasma glucagon between protein hydrolysates and the maltodextrin control drink (P<0.05). Gluten protein hydrolysate induced the lowest glucagon response. High amino-acid-induced glucagon response does not necessarily go together with low insulin response. Protein hydrolysate source affects AUC for glucagon more profoundly than for insulin, although the protein load used in this study seemed to be at lower level for significant physiological effects.

Lipid, Glycemic, and Insulin Responses to Meals Rich in Saturated,cis-Monounsaturated, and Polyunsaturated (n-3 and n-6) Fatty Acids in Subjects With Type 2 Diabetes

The recommendations for dietary fats in patients with type 2 diabetes are based largely on the impact of fatty acids on fasting serum lipid and glucose concentrations. How fatty acids affect postprandial insulin, glucose, and triglyceride concentrations, however, remains unclear. The objective of this study was to study the effect of fatty acids on postprandial insulin, glucose, and triglyceride responses. Test meals rich in palmitic acid, linoleic acid, oleic acid, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and containing 1,000 kcal each were administered in a randomized crossover design to 11 type 2 diabetic subjects. Serum insulin, glucose, and triglyceride concentrations were measured for 360 min. All subjects received an isoenergetic diet of constant composition throughout the study. According to repeated-measures ANOVA, the insulin (P = 0.0002) but not glucose (P = 0.10) response was significantly different between meals. The insulin response was lower to meals rich in oleic acid or EPA and DHA than to meals rich in palmitic acid or linoleic acid (P < 0.01). The triglyceride response did not reach statistical significance (P = 0.06) but tended to be lower with EPA and DHA than with the other fatty acids. Similar trends were seen for area under the curve (AUC) and incremental AUC for serum insulin and triglycerides, but the differences were not significant. In comparison with palmitic acid and linoleic acid, oleic acid or EPA and DHA may modestly lower insulin response in patients with type 2 diabetes without deteriorating the glucose response. EPA and DHA may also reduce the triglyceride response.

Insulin Secretion From Pancreatic Islets in Fibrin Glue Clots at Different Fibrinogen and Thrombin Concentrations

Background Fibrin glue has proven to be a good delivery system for cell transplantation but the factors that influence the fibrin-cell relationships are not well understood. The purpose of this study was to assess the effect of different concentrations of fibrin glue components (thrombin and fibrinogen) on the function of pancreatic islets. Method Islets were isolated from rat pancreata and combined with 6 different fibrin glue formulations. Each islet sample was incubated sequentially with RPMI containing low and high glucose, and culture supernatants were harvested for insulin determination using enzyme-linked immunosorbent assay (ELISA). Results The control group (no fibrin glue) and group 3 (with thrombin 50 U/mL and fibrinogen 10 mg/mL) had the highest insulin secretion in response to glucose stimulation. These were followed by groups 5 and 4 with 2.6 and 1.8 stimulation indexes, respectively. Group 2 (with thrombin 50 U/mL and fibrinogen 5 mg/mL) and group 6 (commercial kit with thrombin 250 U/mL and fibrinogen 75–115 mg/mL) had the lowest insulin response after glucose stimulation. Conclusion This study demonstrates that different fibrin glue formulations significantly impact pancreatic islets function. In the future, when using fibrin glue as a carrier for pancreatic islet transplantation, lower concentrations of fibrinogen and thrombin are recommended to obtain more viable and functional grafts.

Putting your genes on a diet: the molecular effects of carbohydrate

Traditionally, food is thought to influence human health through its nutrient content, whereas drugs are recognized to act through molecular pathways. However, consumption of a meal stimulates the release of numerous hormones that can powerfully affect signal transduction and gene function. The article by Kallio et al (1) in this issue of the Journal highlights this possibility by demonstrating changes in gene expression in individuals consuming diets with different effects on postprandial insulin concentrations. The authors randomly assigned adults with features of the metabolic syndrome to a rye-pasta (low insulin response) or an oat-wheat-potato (high insulin response) diet for 12 wk. The diets were designed to be similar in energy, fiber, and macronutrient contents, although modest differences in fiber, carbohydrate, and protein contents were documented by food records. Gene expression in subcutaneous fat was evaluated at baseline and at 12 wk with microarrays and quantitative polymerase chain reaction. In individuals in the low-insulin-response group, 71 genes showed decreased expression and none showed increased expression. Of particular interest, several down-regulated genes have links to insulin-signaling pathways and apoptosis. In contrast, in individuals in the high-insulin-response group, 62 genes showed increased expression and none showed decreased expression. Prior microarray studies found differences in gene expression between overweight and lean individuals (2) and after energy restriction (3); however, changes in the ratio of fat to carbohydrate did not alter gene expression (3). The study by Kallio et al makes a significant contribution to the literature by demonstrating the potentially major effects of dietary composition on gene regulation, independent of energy intake and body weight. Two specific findings concerning the low-insulin-response diet merit particular attention: the down-regulation of both hormonesensitive lipase (HSL) and TCF7L2. HSL, a key enzyme in the release of fatty acids from adipose tissue, has been proposed to affect body weight and metabolic variables. Mice made deficient in HSL by genetic manipulation are resistant to geneticor diet-induced obesity (4, 5). Women carrying an allele associated with decreased HSL activity have lower fasting and simulated insulin concentrations, and men with this allele have lower nonesterified fatty acid concentrations (6). In light of these data, proteins involved in lipolysis have become targets of drug development for the treatment of obesity and the metabolic syndrome. Thus, decreased HSL activity might mediate some of the purported benefits of diets designed to lower insulin secretion. The transcription factor TCF7L2 is the strongest known genetic predictor of type 2 diabetes. A microsatellite within intron 3 of this transcription factor occurs with increased frequency in individuals with type 2 diabetes, which corresponds to an estimated population attributable risk of 21% (7). Although the mechanisms involved in disease risk have not been fully elucidated, TCF7L2 affects the Wnt signaling pathway and may be critical for glucagon-like peptide 1 (GLP-1) secretion by intestinal endocrine L cells. Decreased secretion of GLP-1 appears to play a role in the development of type 2 diabetes, and GLP-1 agonists have recently been developed for the treatment of diabetes. The present study has direct implications concerning our understanding of the dietary glycemic index (GI). The GI is a system for classifying carbohydrate-containing foods according to how blood glucose concentrations change in the postprandial period (reviewed in reference 8). High-GI meals produce greater postprandial insulin concentrations and C-peptide excretion than do nutrient-controlled low-GI meals. Observational and interventional studies have linked GI to the risk of obesity, diabetes, heart disease, and cancer, although the topic remains much debated. One factor contributing to this ongoing controversy is the relative paucity of data regarding the relevant molecular mechanisms. If differences in insulin secretion mediate the genetic effects observed by Kallio et al, similar effects would be expected to occur with both low-GI and high-GI diets. This possibility is supported by a human study and several rodent studies, which showed potentially beneficial changes in the expression of HSL and other relevant genes with a low-GI diet (8, 9). Several methodologic issues should be considered in the interpretation of this study. Microarray analyses have well-known technical limitations and statistical problems, especially when involving small sample sizes (10). The unidirectional change in gene expression within each diet group provides some grounds

Dietary carbohydrate modification induces alterations in gene expression in abdominal subcutaneous adipose tissue in persons with the metabolic syndrome: the FUNGENUT Study

Background: Diets rich in whole-grain cereals and foods with a low glycemic index may protect against type 2 diabetes, but the underlying molecular mechanisms are unknown.Objective: The main objective was to test whether 2 different carbohydrate modifications—a rye-pasta diet characterized by a low postprandial insulin response and an oat-wheat-potato diet characterized by a high postprandial insulin response—affect gene expression in subcutaneous adipose tissue (SAT) in persons with the metabolic syndrome.Design: We assessed the effect of carbohydrate modification on SAT gene expression in 47 subjects [24 men and 23 women with a mean (±SD) age of 55 ± 6 y] with the features of the metabolic syndrome in a parallel study design. The subjects had a mean (±SD) body mass index (kg/m2) of 32.1 ± 3.8 and a 2-h plasma glucose concentration of 8.0 ± 2.3 mmol/L. Adipose tissue biopsies were performed, and oral-glucose-tolerance tests and other biochemical measurements were conducted before and after the intervention.Results: We detected 71 down-regulated genes in the rye-pasta group, including genes linked to insulin signaling and apoptosis. In contrast, the 12-wk oat-wheat-potato diet up-regulated 62 genes related to stress, cytokine-chemokine–mediated immunity, and the interleukin pathway. The insulinogenic index improved after the rye-pasta diet (P = 0.004) but not after the oat-wheat-potato diet. Body weight was unchanged in both groups.Conclusions: Dietary carbohydrate modification with rye and pasta or oat, wheat, and potato differentially modulates the gene expression profile in abdominal subcutaneous adipose tissue, even in the absence of weight loss.

Effect of regular walking exercise on glucose tolerance and insulin response to i.v. glucose infusion in growing beef steers

ABSTRACTThe purpose of the present paper was to investigate the effect of regular walking exercise on glucose tolerance and insulin response to i.v. glucose infusion in growing beef steers. Four crossbred beef steers walked on a treadmill during a 6 week exercise period (1.2 km/h, 1 h/day and 5 days/week). The changes in plasma glucose and insulin levels following glucose infusion were analyzed immediately prior to (bodyweight: 260.4 ± 24.2 kg) and after (295.7 ± 30.1 kg) the exercise period. The basal levels of plasma glucose (86.4 vs. 82.0 mg/dL, P = 0.040) and insulin (24.5 vs. 14.3 μU/mL, P = 0.016) were significantly lower after the exercise period. Further, the increase in the levels of plasma glucose (420.4 vs. 280.8 mg/dL, P &lt; 0.001) and insulin (94.5 vs. 73.1 μU/mL, P = 0.028) following the glucose infusion decreased after the exercise period. The area under the curve of plasma glucose (108.8 vs. 62.9 mg/dL per min, P &lt; 0.001) and insulin (53.6 vs. 29.7 μU/mL per min, P = 0.018) indicated more rapid clearance of exogenous glucose and less insulin secretion for glucose clearance after the exercise period. These results suggest that regular exercise improves glucose tolerance, with lower insulin response to glucose infusion in growing steers, as observed in rodents and humans.

Visceral Fatness and Insulin Sensitivity in Women With a Previous History of Gestational Diabetes Mellitus

The purpose of this study was to investigate the insulin sensitivity and visceral fatness in women with previous gestational diabetes mellitus (GDM), who are prone to develop type 2 diabetes. A 75-g oral glucose tolerance test (OGTT) performed 1 year postpartum identified 21 GAD(-) women with previous GDM and impaired glucose tolerance (GDM-IGT). Sixty age- and BMI-matched women with normal glucose tolerance (GDM-NGT) were selected by 1:3 matching to the GDM-IGT group. Another 18 women with normal glucose metabolism during a previous pregnancy and no family history of diabetes were recruited as the normal control group. Age and BMI matching was performed using a range of +/-1.0 years and +/-1.0 kg/m(2), respectively. Total body fat was measured by tetrapolar bioelectrical impedance, and visceral fat was determined using a single cut of a computed tomography scan. Insulin sensitivity was determined by the minimal model technique using the frequently sampled intravenous glucose tolerance test. One year postpartum, visceral fat was greater in the GDM-IGT group than in the age- and BMI-matched GDM-NGT or normal control groups. The insulin sensitivity index was lower in the GDM-IGT group than in the GDM-NGT or normal control groups. beta-Cell function, as measured by the acute insulin response to glucose, was also lower in GDM-IGT. High body fat content, especially visceral fat content, and a low insulin response to glucose seem to contribute simultaneously to the development of impaired glucose metabolism in Korean women with previous GDM.

Propionate Tolerance Test for Determination of Insulin Secretion in a Hyperglycemic japanese Black Steer

A propionate tolerance test (PTT) was used to determine the pathophysiology of a Japanese Black steer with hyperglycemia. In the hyperglycemic steer, a low insulin secretion was confirmed by a glucose tolerance test (GTT), so that the hyperglycemic steer was diagnosed as insulin-dependent diabetes mellitus. Although the plasma insulin concentration in the control cattle increased in response to propionate stimulation, a low insulin response to PTT was observed in the diabetic steer. The fact that both PTT and GTT determined that the diabetic steer had low insulin secretion suggests that the PTT might be an effective diagnostic tool for diabetes mellitus in cattle.

Effect of cocoa and green tea consumption on glucoregulatory biomarkers in insulin resistant men and women

In vivo and in vitro research has shown that tea and cocoa consumption may have an impact on the glucoregulatory system. While the specific mechanism of action of tea and cocoa on glucoregulatory biomarkers is uncertain, there has been speculation that dietary polyphenols may have an effect. This pilot study investigated if there was a dose-response effect of cocoa procyanidins (CP) on glucoregulatory biomarkers and compared the effect of cocoa and tea polyphenols on these outcomes. As part of a randomized crossover design, 20 subjects (10 men, 10 women) each consumed a controlled diet at weight maintenance along with 5 treatment beverages: high dose cocoa (900 mg CP), medium dose cocoa (400 mg CP), low dose cocoa (200 mg CP) control cocoa (22 mg CP), and green tea. Each subject consumed the treatments with breakfast and the evening meal for 5 days. On the sixth day subjects underwent an oral glucose tolerance test (OGTT). Biomarkers measured were glucose, insulin, insulin sensitivity index (ISI), and homeostasis model assessment of insulin resistance (HOMA-IR). The OGTT confirmed that 12, 7, and 1 subjects were insulin resistant (IR), normal, and diabetic, respectively. Results showed no significant changes in glucose and insulin after consumption of the cocoa treatments. Green tea compared to cocoa lowered glucose (p=0.0003) and elicited a lower insulin response (p=0.0157) in normal subjects but not in IR subjects. Cocoa and green tea did not affect ISI or HOMA-IR. Consumption of cocoa and green tea had no effect on glucoregulatory biomarkers in IR men and women.

Soy foods have low glycemic and insulin response indices in normal weight subjects.

BackgroundFoods with a low glycemic index (GI) may provide a variety of health benefits. The objective of the present study was to measure the GI and insulin index (II) of select soy foods.MethodsThe study was conducted in two parts with low-carbohydrate products being tested separately. In Experiment 1, subjects averaged 23.2 years of age with BMI = 22.0 kg/m2, while subjects in Experiment 2 averaged 23.9 years of age with BMI = 21.6 kg/m2. The reference (glucose) and test foods were served in portions containing 10 g of carbohydrates in Experiment 1 (two test foods) and 25 g of carbohydrates in Experiment 2 (four test foods). Subjects consumed the reference food twice and each test food once. For each test, subjects were instructed to consume a fixed portion of the reference food or test food together with 250 g of water within 12 min. Blood samples were collected before each test and at 15, 30, 45, 60, 90, and 120 min after consumption of reference or test foods to quantify glucose and insulin. Two-hour blood glucose and plasma insulin curves were constructed and areas under the curves were calculated. GI and II values for each subject and test food were calculated.ResultsIn Experiment 1, both low-carbohydrate soy foods were shown to have significantly (P < 0.05) lower GI and II values than the reference food. In Experiment 2, three of the four test foods had significantly (P < 0.05) lower GI and II values than the reference food.ConclusionAll but one of the soy foods tested had a low GI, suggesting that soy foods may be an appropriate part of diets intended to improve control of blood glucose and insulin levels.

Serum resistin increases in a postprandial state during liquid meal challenge test in healthy human subjects

The role of resistin in humans is controversial although resistin has been linked to atherosclerotic and inflammatory processes. In rodents, resistin expression is suppressed after food restriction while central administration of resistin promotes short-term satiety. However, the nature of postprandial responses in circulating resistin in humans is unknown. Therefore, we investigated postprandial resistin concentrations in a pilot study in 19 healthy subjects and 19 controls matched for age and body mass index (BMI). Serum resistin, insulin and non-esterified fatty acids (NEFA) concentrations as well as plasma glucose and triglycerides were repeatedly assessed before and after ingestion of an isocaloric standardized liquid meal during a 300 min period.After consumption of liquid meal, serum resistin levels increased compared to fasting control (p=0.037). Postprandial plasma glucose and serum insulin increased (p<0.001) with lower glucose responses in females (p=0.001) and lower insulin responses in males (p=0.012). Plasma triglycerides increased and serum NEFA decreased with similar gender responses (p=0.025 and p<0.001, respectively). Serum resistin was not correlated to glucose, insulin, triglyceride, and NEFA responses to liquid meal challenge tests. The present data suggest that serum resistin increases postprandially in healthy humans. Additional studies are needed to elucidate normal 24-h daytime profiles in humans and differential response of serum resistin to macronutrient composition of meals.

Acute caffeine ingestion does not impair glucose tolerance in persons with tetraplegia

Acute caffeine (Caf) ingestion impairs glucose tolerance in able-bodied humans during an oral glucose tolerance test (OGTT). The mechanism responsible for this effect remains unclear, however, it is suggested to be due to the accompanying increase in epinephrine concentration. We examined whether or not Caf would elicit a glucose intolerance in persons with tetraplegia (TP) who do not exhibit an increased epinephrine response following Caf ingestion. All TP [n = 14; 9 incomplete (Inc) lesion, 5 complete (Com) lesion] completed two OGTT 1 h after consuming either gelatin (Pl) or Caf capsules (dose = 4 mg/kg). Blood samples were collected at baseline (time = 0 min), 1 h after capsule ingestion (time = 60 min), and every 30 min during the OGTT (time = 90-180 min). Glucose, insulin, proinsulin, and C-peptide responses were similar (P > 0.05) between treatments, demonstrating no effect of Caf on glucose tolerance. This lack of a Caf effect may be due to the low epinephrine concentration that remained unchanged (P > 0.05) throughout all experiments. Interestingly, the Com exhibited a 50% higher glucose response (P <or= 0.05) and a 46% (P > 0.05) lower insulin response (vs. Inc), suggesting a more pronounced glucose intolerance within this subgroup. Furthermore, nine TP (5 Com, 4 Inc) had glucose levels of >or= 7.8 mM at the end of the OGTT (time = 180 min), classifying them as glucose intolerant. In summary, acute Caf ingestion does not increase epinephrine concentration or impair glucose tolerance in TP.

Plasma ghrelin levels after two high-carbohydrate meals producing different insulin responses in patients with metabolic syndrome

Ghrelin is an orexigenic peptide produced in the stomach and its plasma levels are decreased acutely in response to ingested nutrients. To further clarify the role of insulin on ghrelin secretion, the present study was designed to investigate whether circulating ghrelin is affected differently by two mixtures of whole-grain breads known to produce low or high insulin responses in obese non-diabetic subjects with metabolic syndrome. After an overnight fast eight obese subjects with the metabolic syndrome (3 men and 5 women; BMI 33.7 ± 0.7 kg/m 2; age 55.6 ± 1.8 y) received two different meals consisting of whole-grain rye or wheat breads. The comparison group (3 men and 5 women; BMI 22.5 ± 0.5 kg/m 2; age 26.0 ± 0.9 y) received a wheat bread meal. Blood samples were collected postprandially at time intervals for 2 h. Feelings of hunger and satiety were analyzed using the visual analogue scales. Ghrelin concentrations decreased after bread meals in lean individuals, but not in obese individuals with the metabolic syndrome. Despite the difference in plasma insulin response, there was no difference in plasma ghrelin or feelings of hunger and satiety in patients with metabolic syndrome. After both rye and wheat bread meals, the decrease in ghrelin concentrations seen in normal-weight individuals after wheat bread meal was absent in subjects with metabolic syndrome. Despite the different plasma insulin response in obese patients, ghrelin levels did not change in response to either type of bread meals. In addition, ghrelin levels did not correlate with insulin, glucose, HOMA1-IR and satiety and hunger ratings in either study groups. This indicates that regulation of ghrelin might be altered in obese patients with metabolic syndrome independently of insulin.

Impact of Dietary Patterns and Interventions on Cardiovascular Health

Dietary recommendations are a key element in the management of cardiovascular disease. Evidence is mounting that certain dietary patterns can influence cardiovascular health by modifying risk factors such as obesity, dyslipidemia, and hypertension, as well as factors involved in systemic inflammation, insulin sensitivity, oxidative stress, endothelial function, thrombosis, and cardiac rhythm.1,2 In recent years, numerous dietary fads have emerged, in part as a response to the rising prevalence of obesity in the United States.3 In the present study, we review the various dietary portfolios that have emerged in the literature and the major studies that investigated their effectiveness in modifying cardiovascular risk. Currently, the typical American diet is estimated to derive 49% of its calories from carbohydrates, 34% from fat, and 12% to 16% from protein.4 Proposals to alter the proportions and/or types of macronutrients in this diet have been made for weight loss and cardiovascular health (Table 1).5–12 For weight management, for example, the strategy recommended by most medical groups entails the intake of a low-calorie, low-fat diet. The concept of fat restriction for weight management stems from traditional calorimetric measurements, which assign greater energy values to fat (&9 kcal/g) and less to carbohydrate and protein (&4 kcal/g). The low-calorie concept, on the other hand, is an intuitive technique to induce negative energy balance and has been adopted by some commercialized weight loss programs such as Weight Watchers International. View this table: TABLE 1. Various Dietary Patterns, Including Those Popularized Commercially and Those Investigated by Observational Studies and Clinical Trials One alternative proposed for weight loss is the low-carbohydrate diet. This was first described by William Banting13 in the 1860s and recently has received much attention in the form of the Atkins’, Stillman, Protein Power Lifeplan, and Zone diets. The Atkins’ diet begins with a weight-loss …

Japanese IGT Subjects with High Insulin Response Are Far More Frequently Associated with the Metabolic Syndrome Than Those with Low Insulin Response

Impaired glucose tolerance (IGT) represents a prediabetic state positioned somewhere between normal glucose tolerance and diabetes, which is also assumed to make individuals in this state highly susceptible to atherosclerotic disease. IGT also accounts for a highly heterogeneous population, with the condition varying from individual to individual. In this study, we stratified subjects with IGT by their insulin response and compare the pathology of IGT when it is associated with high or low insulin response to gain insight into the diverse pathology of IGT. Of the male corporate employees who underwent 75 g OGTT at the corporation's healthcare center, 150 individuals diagnosed with IGT (isolated IGT, combined IGT and IFG) comprised our study subjects. The study subjects were stratified into four quartiles by percentile AUC for insulin, and those in the 25th or less percentile were defined as the low insulin response group (n = 37), vs those in the 76th or greater percentile defined as the high insulin response group (n = 38), and these groups were compared. There was no significant difference observed between the two groups in regard to post-OGTT glucose response and area under the glucose curve. However, the high insulin response group was associated with higher BMI, subcutanesous fat area, uric acid levels, HOMA-beta cell values, and delta insulin/delta glucose (30 min) than the low insulin response group. The number of risk factors for the metabolic syndrome detected (as defined by the ATPIII diagnostic criteria) per subject was 2.84 +/- 0.17 and 2.08 +/- 0.20, respectively, in the high insulin response group and in the low insulin response group, with the number significantly (p < 0.05) higher in the high insulin response group. Furthermore, the incidence of the metabolic syndrome as defined by the ATPIII diagnostic criteria was 63.2% (24/38) in the high insulin response group vs 32.4% (12/27) in the low insulin response group, with the incidence significantly (p < 0.01) higher in the high insulin response group. Likewise, the incidence of the metabolic syndrome as defined by the Japanese diagnostic criteria was found to be significantly (p < 0.05) higher in the high insulin response group at 50% (19/38) compared to 27.0% (10/37) in the low insulin response group. Our study findings suggest that IGT subjects with high insulin response and those with low insulin response vary greatly in regard to the number of atherosclerotic risk factors complicated and the frequency with which they are associated with the metabolic syndrome. It is also shown in middle-aged Japanese males that of the two forms of IGT, IGT with high insulin response is more closely linked to the pathogenesis of atherosclerotic cardiovascular disease.