Homeostasis Model Assessment Of Beta-cell Function Research Articles

Superiority of the triglyceride glucose index over the homeostasis model in predicting metabolic syndrome based on NHANES data analysis

The triglyceride-glucose (TyG) index is a simple and inexpensive new marker of insulin resistance that is being increasingly used for the clinical prediction of metabolic syndrome (MetS). Nevertheless, there are only a few comparative studies on its predictive capacity for MetS versus those using the traditional homeostasis model assessment (HOMA). We conducted a cross-sectional study using a database from the National Health and Nutrition Examination Survey (1999 March to 2020 pre-pandemic period). Using statistical methods, we compared the predictive abilities of the TyG index and HOMA (including HOMA of insulin resistance [HOMA-IR] and HOMA of beta-cell function [HOMA-β]) for MetS. A total of 34,195 participants were enrolled and divided into the MetS group (23.1%) or no MetS group (76.9%) according to the International Diabetes Federation (IDF) diagnostic criteria. After applying weighted data, the baseline characteristics of the population were described. Following the exclusion of medication influences, the final count was 31,304 participants. Receiver operating characteristic curve analysis revealed that while distinguishing between MetS and no MetS, the TyG index had an area under the curve (AUC) of 0.827 (sensitivity = 71.9%, specificity = 80.5%), and the cutoff was 8.75, slightly outperforming HOMA-IR (AUC = 0.784) and HOMA-β (AUC = 0.614) with a significance of P < 0.01. The prevalence of MetS in the total population calculated using the TyG index cutoff value was 30.9%, which was higher than that reported in the IDF diagnostic criteria. Weighted data analysis using univariate and multivariate logistic regression displayed an independent association between elevated TyG and HOMA-IR with the risk of MetS. Subgroup analysis further revealed differences in the predictive ability of the TyG index among adult populations across various genders and ethnicities, whereas such differences were not observed for children and adolescents. The TyG index is slightly better than HOMA in predicting MetS and may identify more patients with MetS; thus, its applications in a clinical setting can be appropriately increased.

Factors Associated with Relapse of Type 2 Diabetes Mellitus after Laparoscopic Sleeve Gastrectomy in Japanese Subjects: A Subgroup Analysis of J-SMART Study

Introduction: Laparoscopic sleeve gastrectomy (LSG) for morbidly obese patients often results in remission of type 2 diabetes (T2DM), but diabetes relapses in some of those patients. The frequency of T2DM relapse in Asians and the factors involved have not been adequately investigated. Methods: The J-SMART study was conducted on 322 Japanese subjects with body mass index (BMI) ≥32 kg/m² who underwent LSG at 10 accredited centers in Japan between 2011 and 2014. Of these, 82 T2DM subjects with diabetes in complete or partial remission at 1 year after LSG and followed postoperatively for 5 years were included in the subgroup analysis and classified into two groups: diabetes remission-maintained and diabetes relapse. Results: The mean age of all included subjects was 49.2 years, median BMI was 41.5 kg/m², and median HbA1c was 6.7%. Compared with the diabetes remission-maintained group, the diabetes relapse group at 5 years after LSG had significantly higher preoperative HbA1c, number of antidiabetic medications, and high-density lipoprotein cholesterol level; and lower BMI and homeostasis model assessment-beta cell function (HOMA-β). As many as 83.0% of the subjects were able to achieve HbA1c <7% at 5 years after LSG, but 26.8% of the subjects had diabetes relapse. Preoperative HbA1c significantly contributed to diabetes relapse (odds ratio 1.54, p = 0.049). In addition, the diabetes relapse group tended to have lower percentage total weight loss (%TWL) at 1 year after LSG and higher percentage weight regain (%WR) from postoperative nadir weight, compared with the diabetes remission-maintained group. The hazard ratio for diabetes relapse was 3.14-fold higher in subjects with %TWL ≥20% and %WR ≥25%, and 5.46-fold higher in those with %TWL <20% and %WR ≥25%, compared with %TWL ≥20% and %WR <25%. Conclusion: While LSG provides a high remission rate for T2DM, relapse is not uncommon. Preoperative HbA1c, poor weight loss, and excess weight regain after LSG contribute to diabetes relapse, suggesting the importance of treatment strategies focusing on these factors.

The effect of omega-3 and vitamin D co-supplementation on glycemic control and lipid profiles in reproductive-aged women with pre-diabetes and hypovitaminosis D: a randomized controlled trial

BackgroundPrediabetes can predispose the individual to type 2 diabetes in the long-term. The present study was conducted to determine the effectiveness of vitamin D and omega-3 co-supplementation on glycemic control and serum lipid profiles in women of reproductive age with prediabetes and hypovitaminosis D.MethodsThe present factorial, triple-blind, clinical trial was conducted on 168 women of reproductive age with prediabetes and hypovitaminosis D. The participants were assigned to four groups based on block randomization method: the placebo group received omega-3 and vitamin D placebos; the omega-3 group took omega-3 supplements and vitamin D placebos; the vitamin D group received omega-3 placebos and vitamin D supplements and the co-supplementation group. The groups received every 2 weeks 50,000 IU pearls of vitamin D and twice-daily doses of 1000-mg omega-3 tablets or placebos for 8 weeks. Dietary intake, physical activity, anthropometric indices and blood biochemical tests were measured at the beginning and end of the study. Analysis was performed using two-way mixed ANOVA.ResultsA significant reduction was observed in fasting glucose, insulin, homeostasis model assessment-beta cell function, weight and waist circumference in the co-supplementation group compared to the other three groups (P < 0.05). Moreover, high-density lipoprotein-cholesterol levels increased significantly in the co-supplementation group compared to the other three groups (P < 0.05). Despite the fact that homeostasis model assessment-insulin resistance, total cholesterol, triglyceride and low-density lipoprotein-cholesterol levels decreased after intervention in the co-supplementation group, there was no significant difference between the groups in these outcomes.ConclusionVitamin D and omega-3 co-supplementation improved fasting serum glucose, insulin, high-density lipoprotein-cholesterol level, homeostasis model assessment-beta cell function, weight and waist circumference in women of reproductive age with prediabetes and hypovitaminosis D. This co-supplementation can therefore be recommended for glycemic control in these women.Trial registration Iranian Registry of Clinical Trials Code: IRCT20100130003226N17. Registered on 9 Feb. 2019

EFFECT OF SPEXIN TREATMENT ON CARDIOMETABOLIC CHANGES IN OBESE TYPE 2 DIABETIC RATS

Background: Spexin is a peptide hormone that was expressed in brain regions and peripheral tissues of many species including human and rat. Several studies investigated its blood level changes with obesity and type 2 diabetes, but few studies assessed its effect on cardiometabolic, histological and morphometric changes in diabetes with some controversies in their results. Objective: To explore the effect of spexin treatment on cardiometabolic, histological and morphometric changes of pancreas and heart tissue in obese type 2 diabetic rats, and the possible mechanisms involved. Materials and Methods: Thirty adult male albino rats were divided randomly into 5 equal groups; control (fed ordinary laboratory chow along this 8 weeks’ study), diabetic [fed high fat diet along this 8 weeks’ study, but at the start of the 4th week, overnight fasted rats were injected with a single streptozotocin injection intraperitoneally (40 mg/kg body weight, dissolved in 0.01M citrate buffer, pH 4.5) to induce diabetes], diabetic metformin-treated [rats were managed as in diabetic group and in addition to that, metformin was given orally (300 mg/kg/day) by oral gavage to rats for 4 weeks from the start of 5th week to the end of 8th week], diabetic vildagliptin treated [rats were manipulated as in diabetic group and in addition to that, vildagliptin was given orally (10 mg/kg/day) using oral gavage to rats for 4 weeks from the start of 5th week to the end of 8th week], and diabetic spexin treated [rats were managed as in diabetic group and in addition to that, spexin dissolved in normal saline was injected intraperitoneally (35 μg/kg/day) for 4 weeks from the start of 5th week to the end of 8th week] groups. For histological, immunohistochemical and morphometric examinations, fresh heart and pancreatic specimens were collected from rats that were sacrificed. Results: In diabetic group, a significant increase was detected in final body mass index, serum glucose, serum insulin, homeostasis model assessment-insulin resistance, serum total cholesterol, serum triglycerides, serum low density lipoprotein, atherogenic index, serum dipeptidyl peptidase-IV, serum tumor necrosis factor alpha serum interleukin-1 beta, serum malondialdehyde, serum lactate dehydrogenase, serum creatine kinase-myoglobin binding and mean arterial blood pressure, with a significant decrease in homeostasis model assessment-beta cell functionserum high density lipoprotein, serum superoxide dismutase and serum spexin in comparison to that in the control group. With spexin treatment (as well as with the administration of standard drugs metformin and vildagliptin), all these changes were reversed significantly in comparison with those in the diabetic group. Diabetes induced histopathological changes in cardiac muscle and pancreatic structure which were ameliorated by treatment with spexin as well as with the standard anti-diabetic drugs (metformin and vildagliptin). The morphometric analysis confirmed the histopathological results, as a statistically significant difference was detected in area percent of collagen deposition, area percent of insulin immune-reaction in pancreas and cardiac muscle Bax expression between both diabetic group and all other groups, with no statistically significant difference between diabetic metformin treated, diabetic vildagliptin treated and diabetic spexin treated groups. Conclusion: Spexin ameliorated diabetes induced deleterious cardiometabolic, histopathological and morphometric disturbances. The anti-obesity, dipeptidyl peptidase-IV inhibitory, hypoglycemic, hypolipidemic, antioxidant, anti-inflammatory and cardio-protective properties of spexin may contribute to its useful effects.

EFFECT OF SPEXIN TREATMENT ON CARDIOMETABOLIC CHANGES IN OBESE TYPE 2 DIABETIC RATS

Background: Spexin is a peptide hormone that was expressed in brain regions and peripheral tissues of many species including human and rat. Several studies investigated its blood level changes with obesity and type 2 diabetes, but few studies assessed its effect on cardiometabolic, histological and morphometric changes in diabetes with some controversies in their results. Objective: To explore the effect of spexin treatment on cardiometabolic, histological and morphometric changes of pancreas and heart tissue in obese type 2 diabetic rats, and the possible mechanisms involved. Materials and Methods: Thirty adult male albino rats were divided randomly into 5 equal groups; control (fed ordinary laboratory chow along this 8 weeks’ study), diabetic [fed high fat diet along this 8 weeks’ study, but at the start of the 4th week, overnight fasted rats were injected with a single streptozotocin injection intraperitoneally (40 mg/kg body weight, dissolved in 0.01M citrate buffer, pH 4.5) to induce diabetes], diabetic metformin-treated [rats were managed as in diabetic group and in addition to that, metformin was given orally (300 mg/kg/day) by oral gavage to rats for 4 weeks from the start of 5th week to the end of 8th week], diabetic vildagliptin treated [rats were manipulated as in diabetic group and in addition to that, vildagliptin was given orally (10 mg/kg/day) using oral gavage to rats for 4 weeks from the start of 5th week to the end of 8th week], and diabetic spexin treated [rats were managed as in diabetic group and in addition to that, spexin dissolved in normal saline was injected intraperitoneally (35 μg/kg/day) for 4 weeks from the start of 5th week to the end of 8th week] groups. For histological, immunohistochemical and morphometric examinations, fresh heart and pancreatic specimens were collected from rats that were sacrificed. Results: In diabetic group, a significant increase was detected in final body mass index, serum glucose, serum insulin, homeostasis model assessment-insulin resistance, serum total cholesterol, serum triglycerides, serum low density lipoprotein, atherogenic index, serum dipeptidyl peptidase-IV, serum tumor necrosis factor alpha serum interleukin-1 beta, serum malondialdehyde, serum lactate dehydrogenase, serum creatine kinase-myoglobin binding and mean arterial blood pressure, with a significant decrease in homeostasis model assessment-beta cell functionserum high density lipoprotein, serum superoxide dismutase and serum spexin in comparison to that in the control group. With spexin treatment (as well as with the administration of standard drugs metformin and vildagliptin), all these changes were reversed significantly in comparison with those in the diabetic group. Diabetes induced histopathological changes in cardiac muscle and pancreatic structure which were ameliorated by treatment with spexin as well as with the standard anti-diabetic drugs (metformin and vildagliptin). The morphometric analysis confirmed the histopathological results, as a statistically significant difference was detected in area percent of collagen deposition, area percent of insulin immune-reaction in pancreas and cardiac muscle Bax expression between both diabetic group and all other groups, with no statistically significant difference between diabetic metformin treated, diabetic vildagliptin treated and diabetic spexin treated groups. Conclusion: Spexin ameliorated diabetes induced deleterious cardiometabolic, histopathological and morphometric disturbances. The anti-obesity, dipeptidyl peptidase-IV inhibitory, hypoglycemic, hypolipidemic, antioxidant, anti-inflammatory and cardio-protective properties of spexin may contribute to its useful effects.

Factors That Influence Pancreatic Beta Cell Function and Insulin Resistance in Newly Diagnosed Type 2 Diabetes Patients: A Sub-Analysis of the MARCH Trial.

IntroductionThe Metformin and Acarbose in Chinese as the initial Hypoglycemic treatment (MARCH) trial has demonstrated a similar efficacy in HbA1c reduction between acarbose and metformin treatments in newly diagnosed type 2 diabetes mellitus (T2DM) patients. The current sub-analysis of the MARCH trail aims to evaluate the baseline characteristics that may influence the improvement of pancreatic β-cell function and insulin resistance after acarbose therapy in Chinese patients with newly diagnosed T2DM.MethodsOf the 784 patients who entered the MARCH trail, 391 were assigned to the acarbose therapy group; 304 of these completed 48 weeks of follow-up of acarbose therapy. At 48 weeks, on the basis of the tertiles of change in homeostasis model assessment–beta cell function (∆HOMA-β) and homeostasis model assessment–insulin resistance (∆HOMA-IR), the subjects were divided into lowly, mediumly, and highly improved groups.ResultsIn the highly improved HOMA-β group, patients had higher systolic blood pressure (SBP), 2-h postprandial blood glucose (PBG), hemoglobin A1c (HbA1c), and lower high-density lipoprotein cholesterol (HDL-c), fasting serum insulin (FINS) concentration, and HOMA-IR in comparison to the lowly improved group (p < 0.05). A positive correlation was observed between HbA1c, SBP, and highly improved ∆HOMA-β (p < 0.05), while an inverse correlation was evident between HDL-c and highly improved ∆HOMA-β (p < 0.05). The highly improved HOMA-IR group had a significantly higher body mass index (BMI), fasting blood glucose (FBG), FINS concentration, and HOMA-β in comparison to the lowly improved group (p < 0.05). A positive correlation was observed between FBG, waist circumference, and highly improved HOMA-IR (p < 0.05).ConclusionNewly diagnosed T2DM Chinese patients with lower baseline HDL-c and higher HbA1c and SBP values are more likely to achieve improvement in beta cell function whereas baseline fasting blood glucose and waist circumference were the significant factors associated with improvement in insulin resistance with acarbose therapy.Trial RegistrationThe clinical trial registry number was ChiCTR-TRC-08000231.

Paraoxonase-2 variants potentially influence insulin resistance, beta-cell function, and their interrelationships with alanine aminotransferase in type 2 diabetes.

Background:The aim of this study was to determine whether insulin resistance, beta-cell function, and their associations with alanine aminotransferase (ALT) are affected by the functional variants of paraoxonase-2 (PON2) as an intracellular antioxidant in patients with type 2 diabetes (T2D).Materials and Methods:Quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment for beta-cell function (HOMA-BCF) were assessed in T2D patients. Insulin levels were determined using ELISA. The variants PON2-A148G and PON2-S311C were genotyped using polymerase chain reaction-based restriction fragment length polymorphism.Results:According to the PON2-G148A variant, ALT was found to be significantly correlated with QUICKI (r = −0.616, P = 0.005) and HOMA-BCF (r = 0.573, P = 0.01) in the GA + GG group; however, the correlations were not statistically significant in the AA genotypes. Based on the genotypes of PON2-S311C, there was a significant correlation between ALT with QUICKI (r = −0.540, P = 0.031) and HOMA-BCF (r = 0.567, P = 0.022) in the SC + CC group. In the multiple adjusted logistic regression analyses, considering the variants PON2-G148A and PON2-C311S as independent variables and QUICKI and HOMA-BCF as the dependent variables, both variants were significantly associated with the QUICKI (P = 0.019 for PON2-G148A and P = 0.041 for PON2-C311S). Furthermore, PON2-C311S remained significantly associated with HOMA-BCF (P = 0.03).Conclusion:These data implicate a role for the functional variants of PON2 in insulin resistance and beta-cell function as well as underscore the effective role of these variants in the associations between them and ALT. Our data contribute to our understanding of the important physiologic functions of PON2 in glucose metabolism and its related metabolic diseases.

Bone remodelling markers in hypertensive patients with and without diabetes mellitus: link between bone and glucose metabolism.

Growing evidence suggests the presence of a complex interplay between hypertension as well as type 2 diabetes mellitus (DM) and osteoporosis. The present study was designed to investigate a possible effect of type 2 DM on bone remodelling markers such as osteoprotegerin and N-terminal propeptide of type 1 collagen (P1NP) in hypertensive patients. The 100 study participants were divided into three groups according to the presence of DM and hypertension: group one included diabetic hypertensive subjects, group 2 included hypertensive subjects without diabetes and group 3 included subjects without hypertension and without DM (controls). Blood sampling for metabolic parameters, including osteoprotegerin, P1NP, adiponectin, fasting glucose, HbA1c , CRP, homeostasis model assessment-insulin resistance, homeostasis model assessment-beta function was performed. Circulating P1NP increased from group 1 to group 3 in a continuous fashion. P1NP was significantly lower in hypertensive subjects with DM (group 1), than in groups 2 and 3 (p < 0.0001). P1NP, was marginally lower in diabetic hypertensive subjects as compared with nondiabetic subjects with hypertension (p = 0.079). Circulating osteoprotegerin did not differ significantly between groups (p = 0.593). In the present study, bone formation marker, P1NP, was significantly lower in diabetic hypertensive subjects as compared with nondiabetic subjects with and without hypertension. P1NP was inversely associated with parameters of glucose homeostasis such as fasting glucose, HbA1c and positively with homeostasis model assessment-beta cell function. Type 2 DM was associated with an adverse effect on bone formation independently of age, sex and exposure to anti-diabetic drugs.

Serum osteocalcin level is positively associated with insulin sensitivity and secretion in patients with type 2 diabetes

ObjectiveBone is being recognized as an endocrine organ. Although previous animal studies showed that osteocalcin stimulated the expression of insulin in islets and of adiponectin in adipocytes with increased insulin secretion and sensitivity, the associations of serum osteocalcin with those parameters remain unclear in humans. MethodsIn this cross-sectional study, we employed 101 postmenopausal women and 152 men with type 2 diabetes, who have not taken drugs for diabetes or osteoporosis. We also examined 75g oral glucose tolerance test (OGTT) in 18 postmenopausal women and 20 men who visited our clinic for medical check-up for diabetes. ResultsIn both postmenopausal women and men, multiple regression analysis adjusted for age, body mass index, and serum creatinine showed that serum osteocalcin level was significantly and negatively associated with fasting plasma glucose, HbA1c, %Trunk fat, and homeostasis model assessment (HOMA) for insulin resistance (p<0.05), and positively with HOMA for beta-cell function (p<0.05). In addition, significant positive association of serum osteocalcin level with serum adiponectin level was found in postmenopausal women (p<0.05), but not in men. In the OGTT examinations, subjects were divided into tertiles by their serum osteocalcin levels in each gender. Postmenopausal women in the lowest tertile showed hyperglycemia and hyperinsulinemia compared to those in the highest tertile after oral glucose loading (p<0.05). Men in the lowest tertile also exhibited hyperinsulinemia (p<0.05), while hyperglycemia was not found. ConclusionThese findings indicate that serum osteocalcin level is positively associated with insulin sensitivity and secretion in Japanese patients with type 2 diabetes.

Effects of One Year Treatment of Vildagliptin Added to Pioglitazone or Glimepiride in Poorly Controlled Type 2 Diabetic Patients

The aim of the study was to compare the effects of vildagliptin added to pioglitazone or glimepiride on metabolic and insulin resistance related-indices in poorly controlled type 2 diabetic patients (T2DM). 168 patients with T2DM were randomized to take either pioglitazone 30 mg once a day plus vildagliptin 50 mg twice a day or glimepiride 2 mg 3 times a day plus vildagliptin 50 mg twice a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment beta-cell function index (HOMA-beta), fasting plasma proinsulin (FPPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), adiponectin (ADN), resistin (R), tumor necrosis factor-alpha (TNF-alpha), and high sensitivity C-reactive protein (Hs-CRP) at their baseline values, and after 3, 6, 9, and 12 months of treatment. We observed a similar improvement of HbA1c, FPG, PPG, and Hs-CRP compared to baseline in the 2 groups. Fasting plasma insulin, FPPr, Pr/FPI ratio, R, and TNF-alpha were significantly decreased and ADN was significantly increased with pioglitazone plus vildagliptin, but not with glimepiride plus vildagliptin. HOMA-IR, and HOMA-beta values obtained with pioglitazone plus vildagliptin were significantly better than the values obtained with glimepiride plus vildagliptin. Pioglitazone plus vildagliptin were found to be more effective in preserving beta-cell function, and in reducing insulin resistance, and inflammatory state parameters.

Efficacy and safety of the dipeptidyl peptidase‐4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy

To evaluate the efficacy and safety of alogliptin, a potent and highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, in combination with glyburide in patients with type 2 diabetes inadequately controlled by sulphonylurea monotherapy. After a 2-week screening period, adult patients 18-80 years of age entered a 4-week run-in/stabilization period in which they were switched from their own sulphonylurea medication to an equivalent dose of glyburide (open label) plus placebo (single blind). After the run-in period, patients were randomly assigned to double-blind treatment with alogliptin 12.5 mg (n = 203), alogliptin 25 mg (n = 198), or placebo (n = 99) for 26 weeks. The primary end-point was change from baseline to week 26 in glycosylated haemoglobin (HbA1c). Secondary end-points included clinical response rates and changes in fasting plasma glucose, beta-cell function (fasting proinsulin, insulin, proinsulin/insulin ratio, and C-peptide, and homeostasis model assessment beta-cell function), body weight, and safety end-points [adverse events (AEs), clinical laboratory tests, vital signs and electrocardiographic readings]. The study population had a mean age of 57 years and a mean disease duration of 8 years; it was well balanced for gender (52% women) and was mainly white (71%). The mean baseline HbA1c was approximately 8.1% in each group. Significantly greater least squares (LS) mean reductions in HbA1c were seen at week 26 with alogliptin 12.5 mg (-0.38%) and 25 mg (-0.52%) vs. placebo (+0.01%; p < 0.001), and more patients in the alogliptin 25-mg group had HbA1c levels < or =7.0% at week 26 (34.8%, p = 0.002) vs. placebo (18.2%). Proportionately more patients in the alogliptin 12.5 mg (47.3%) and 25 mg (50.5%) groups had an HbA1c reduction > or =0.5% from baseline compared with patients in the placebo group (26.3%; p < 0.001). Minor improvements in individual markers of beta-cell function were seen with alogliptin, but no significant treatment group differences were noted relative to placebo. Minor LS mean changes in body weight were noted across groups (placebo, -0.20 kg; alogliptin 12.5 mg, +0.60 kg; alogliptin 25 mg, +0.68 kg). AEs were reported for 63-64% of patients receiving alogliptin and 54% of patients receiving placebo. Few AEs were treatment limiting (2.0-2.5% across groups), and serious AEs (2.0-5.6%) were infrequent, similar across groups, and generally considered not related to treatment. The incidences of hypoglycaemia for placebo, alogliptin 12.5 mg and alogliptin 25 mg groups were 11.1, 15.8 and 9.6% respectively. In patients with type 2 diabetes inadequately controlled by glyburide monotherapy, the addition of alogliptin resulted in clinically significant reductions in HbA1c without increased incidence of hypoglycaemia.

The central issue? Visceral fat mass is a good marker of insulin resistance and metabolic disturbance in women with polycystic ovary syndrome

To establish whether visceral fat mass is the most significant variable correlating with insulin resistance and other metabolic parameters in women with polycystic ovary syndrome (PCOS). Prospective cross-sectional trial. Reproductive medicine clinic. Forty women with anovulatory PCOS. Measurements were taken at recruitment, and analysis was performed to define correlations between the outcome measures and the explanatory variables. Visceral and subcutaneous fat by computed tomography scan, insulin resistance, anthropometric measures, markers of the metabolic syndrome and androgens. Strong linear correlation of visceral fat to insulin resistance (r = 0.68, P < 0.001) was observed. There were also statistically significant correlations with fasting insulin (r = 0.73, P < 0.001), homeostasis model assessment beta-cell function (r = 0.50, P = 0.007), triglycerides (r = 0.45, P = 0.003), high-density lipoprotein cholesterol (r = -0.42, P = 0.007), urate (r = 0.47, P = 0.002), Sex hormone binding globulin (r = -0.39, P = 0.01) and luteinising hormone (r = -0.32, P = 0.02). There were no significant correlations of testosterone with fat distribution or metabolic parameters. Insulin resistance showed closest correlation to visceral fat mass (r = 0.68, P < 0.001), then to waist circumference (r = 0.62, P < 0.001), with the weakest correlation being waist:hip ratio (r = 0.36, P = 0.01). The best regression model for predicting insulin resistance is with visceral fat mass and triglycerides as the explanatory variables (r = 0.72, P < 0.001). Visceral fat is the most significant variable correlating with metabolic dysfunction in women with PCOS. Our data support the hypothesis that visceral fat either causes insulin resistance or is a very early effect of it. It also implies that reducing visceral fat should reduce insulin resistance which may account for the observations that exercise and weight loss appear to be more effective interventions than pharmacological treatments. The best anthropometric measure of insulin resistance is waist circumference.

Association of multiple risk factors and insulin resistance with increased prevalence of asymptomatic coronary artery disease by an electron-beam computed tomographic study.

The insulin resistance syndrome, consisting of resistance to insulin and several metabolic abnormalities, is associated with an increased risk of symptomatic coronary artery disease. Asymptomatic persons with increased coronary calcification have increased coronary plaque and an increased likelihood of future cardiovascular events. Electron-beam computed tomography-derived coronary artery calcium scores, metabolic and anthropometric parameters, and fasting and stimulated concentrations of glucose and insulin were measured in 1160 asymptomatic men and women. Coronary artery calcium scores were positively correlated with glucose, insulin, and homeostasis model assessment (HOMA) insulin resistance. Calcium scores were positively correlated with intra-abdominal adiposity, age, total cholesterol/high density lipoprotein (HDL) ratio, low density lipoprotein, triglycerides, blood pressure, and HOMA beta cell function and inversely correlated with HDL and peripheral fat. These correlations, except for 2-hour glucose, remained significant for all subjects with fasting serum glucose <126 mg/dL or all subjects with fasting serum glucose 110 mg/dL. In a multivariate analysis, age, sex, family history of premature coronary artery disease, intra-abdominal adiposity, low density lipoprotein, and smoking independently predicted calcium scores. Blood pressure, HDL, triglycerides, glucose, insulin, and HOMA insulin resistance or beta cell function were not independently correlated with coronary artery calcium scores. Asymptomatic individuals with insulin resistance have elevated coronary calcium scores. The association between insulin resistance and coronary calcification persists with impaired glucose tolerance and normal fasting serum glucose. Central/visceral adiposity may be a determinant of insulin resistance and atherosclerosis even in asymptomatic nondiabetic persons.

Impaired beta-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients.

Abnormal glucose tolerance is often demonstrated in acromegalic patients. Although insulin resistance is a common feature of acromegaly, it remains unclear whether the extent of insulin resistance per se determines the abnormal glucose tolerance. In order to elucidate this issue, we investigated insulin sensitivity and beta-cell function in acromegalic patients. Twenty-four acromegalic patients were studied in comparison with 24 healthy control subjects. To estimate insulin sensitivity and beta-cell function, we used correct homeostasis model assessment (HOMA) model, a computer-solved model. We also investigated the effects of surgical success on both parameters. HOMA insulin sensitivity (HOMA-%S) in the acromegalic patients was 74 +/- 51 (SD)%, significantly lower than that in 24 healthy controls (144 +/- 49%). HOMA-%S in 12 normal glucose tolerance (NGT) patients was 54 +/- 31%, not significantly different from that in impaired glucose tolerance (IGT; n = 11) or diabetes mellitus (DM; n = 1) patients (93 +/- 60%). By contrast, HOMA beta-cell function (HOMA-%beta) in the NGT acromegalic patients was 163 +/- 67%, significantly higher than the IGT/DM acromegalic patients (89 +/- 34%) and the healthy controls (72 +/- 19%). In 11 patients who achieved complete normalization of GH excess after surgery, HOMA-%S significantly increased to control ranges (from 76 +/- 26 to 159 +/- 61%) within 2 weeks after the surgical success. We conclude that insulin sensitivity is reduced to a similar extent in acromegalic patients with normal glucose tolerance and those with impaired glucose tolerance or diabetes. Compensatory hyperfunction of beta-cells appears to counterbalance the reduced insulin sensitivity in the acromegalic patients with normal glucose tolerance but not in those with impaired glucose tolerance or diabetes.

Leptin levels, beta-cell function, and insulin sensitivity in families with congenital and acquired generalized lipoatropic diabetes.

Lipoatropic diabetes (LD) designates a group of syndromes characterized by diabetes mellitus with marked insulin resistance and either a localized or generalized absence of adipose tissue. In this study, we evaluated plasma leptin levels in subjects with congenital generalized lipoatropic diabetes (CGLD, n = 11) or acquired generalized lipoatropic diabetes (AGLD, n = 11), and assessed correlations between leptin levels and estimations of insulin secretion and insulin sensitivity using homeostasis model assessment (HOMA). Leptin levels were 0.86 +/- 0.32, 1.76 +/- 0.78, and 6.9 +/- 4.4 ng/mL in subjects with CGLD, AGLD, and controls (n = 19), respectively (ANOVA P < 0.0001). Specific insulin levels were 154 +/- 172, 177 +/- 137 and 43 +/- 22 pmol/L, respectively (P < 0.0001). Insulin sensitivity was significantly decreased in both groups with LD (P < 0.0001), whereas HOMA beta-cell function was not significantly different when compared with controls. Leptin levels were significantly correlated with body mass index, insulin levels, and HOMA beta-cell function, and inversely correlated with insulin sensitivity in control subjects but not in subjects with generalized LD. In conclusion, decreased leptin levels were observed in subjects with generalized LD, with a trend towards lower levels in the acquired than in the congenital form (P = 0.06). The temporal relationship between the decrease in leptin levels and the development of lipoatrophy should be investigated in at-risk young relatives of subjects with the acquired forms to assess the usefulness of leptin levels as a marker of lipoatrophy.