Surrogate Measures Of Insulin Resistance Research Articles

New‐onset diabetes mellitus among patients with glomerular diseases

Glomerulonephritis commonly causes kidney failure. Immunosuppressant treatment may be diabetogenic, but data on hyperglycaemia in glomerulonephritis treated with usual clinical care are scant. To assess the epidemiology, risk factors and outcomes for new-onset diabetes among patients with glomerular disease (NODAG). A single-centre retrospective cohort of nondiabetic adults diagnosed with glomerulonephritis between January 2011 and July 2015. Clinical, laboratory and pharmacotherapy data were retrieved from electronic medical records. Using modified American Diabetes Association criteria, the primary outcome of NODAG was present if fasting venous glucose was ≥7 mmol/L for at least two readings, HbA1c was ≥6.5% or if patient required antidiabetic medications. Secondary outcomes were end-stage renal disease, cardiovascular disease and death. NODAG occurred in 48 patients (10.7%); 22 required antidiabetic medication at median 6.2 (interquartile range 1.7, 20.0) months after glomerulonephritis diagnosis. Patients with NODAG had higher prebiopsy fasting glucose, greater proteinuria and lower fasting high-density lipoprotein cholesterol levels. Methylprednisolone and cyclophosphamide were more commonly used among patients with NODAG. In multivariate logistic regression, greater proteinuria (odds ratio 1.08 (95% confidence interval 1.01, 1.16), P = 0.02) and methylprednisolone use (odds ratio 4.02 (95% confidence interval 1.76, 9.18), P = 0.001) were significantly associated with NODAG, independent of the triglyceride/high-density lipoprotein cholesterol ratio as a surrogate measure of insulin resistance. Median follow up was 39.6 (26.9, 57.2) months. Secondary outcomes were not significantly different in patients with and without NODAG. Proteinuria and methylprednisolone were associated with incident diabetes among patients with glomerular disease treated with usual care. At-risk patients should be appropriately counselled and monitored for hyperglycaemia.

High fasting C-peptide levels and insulin resistance in non-lean & non-obese (BMI >19 to < 25 kg/m2) Asian Indians with type 2 diabetes are independently associated with high intra-abdominal fat and liver span

Background and objectivesWe aimed to compare C-peptide levels & measures of insulin resistance in non-lean & non-obese Asian Indian patients with type 2 diabetes (T2DM) vs. non-lean, non-diabetic controls and to correlate with anthropometric measures, volumes of abdominal adipose tissue depots, pancreas, & liver span. MethodsNon-lean, non-obese (BMI >19 and < 25 kg/m2) Asian Indian patients with T2DM, (cases n, 87), diagnosed within one year, on metformin mono therapy, were compared to BMI-matched non-diabetic subjects (controls, n, 37). Measures of glycaemia, insulin and C-peptide levels (fasting and post-prandial), lipid profile, and hepatic transaminases were analysed. Abdominal adipose tissue volumes [subcutaneous & intra-abdominal], pancreatic volume and liver span were assessed using 1.5 Tesla MRI scan. ResultsIn cases, the mean values of HbA1c, fasting and post prandial insulin and C-peptide levels, and 3 measures of insulin resistance were significantly higher than controls, but not for HOMA-B. Higher fasting C-peptide levels correlated significantly with HOMA-IR (r = 0.42, p < 0.001), Fasting Insulin Resistance Index (r = 0.42, p < 0.001), Bennett's Index (r = 0.38, p < 0.05), and volumes of SCAT and IAAT only in cases. The independent predictors of higher fasting C-peptide level were IAAT volume (β = 0.057; p = 0.002), liver span (β = 0.057, p = 0.005) and fasting insulin levels (β = 0.35, p = 0.02). ConclusionHigher fasting and post-prandial C-peptide levels and surrogate measures of insulin resistance in non-obese Asian Indian patients with T2DM are independently associated with IAAT volume and liver span.

Effects of Unfiltered Coffee and Bioactive Coffee Compounds on the Development of Metabolic Syndrome Components in a High-Fat-/High-Fructose-Fed Rat Model.

The literature is inconsistent as to how coffee affects metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. This study aimed to evaluate the effects of unfiltered coffee on diet-induced MetS and investigate whether or not phenolic acids and trigonelline are the main bioactive compounds in coffee. Twenty-four male Sprague‒Dawley rats were fed a high-fat (35% W/W) diet plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water at a dosage equal to 4 cups/day in a human. Compared to the controls, total food intake (p = 0.023) and mean body weight at endpoint (p = 0.016) and estimated average plasma glucose (p = 0.041) were lower only in the coffee group. Surrogate measures of insulin resistance including the overall fasting insulin (p = 0.010), endpoint HOMA-IR (p = 0.022), and oral glucose tolerance (p = 0.029) were improved in the coffee group. Circulating triglyceride levels were lower (p = 0.010), and histopathological and quantitative (p = 0.010) measurements indicated lower grades of liver steatosis compared to controls after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

Serum ferritin levels are associated with insulin resistance in Chinese men and post-menopausal women: the Shanghai Changfeng study.

Associations between ferritin and insulin sensitivity have been described in recent studies. The possible association showed conflicting results by sex and menopausal status. We aimed to investigate the cross-sectional association of ferritin levels with insulin resistance and β-cell function. A total of 2518 participants (1033 men, 235 pre-menopausal women and 1250 post-menopausal women) were enrolled from the Changfeng Study. A standard interview was conducted, as well as anthropometric measurements and laboratory analyses, for each participant. The serum ferritin level was measured using electrochemiluminescence immunoassay. Insulin resistance and β-cell function indices were derived from a homeostasis model assessment. The results showed that the serum ferritin levels were 250·4 (sd 165·2), 94·6 (sd 82·0) and 179·8 (sd 126·6) ng/ml in the men, pre-menopausal and post-menopausal women, respectively. In fully adjusted models (adjusting for age, current smoking, BMI, waist:hip ratio, systolic blood pressure, diastolic blood pressure, TAG, HDL-cholesterol, LDL-cholesterol, log urine albumin:creatinine ratio, leucocytes, alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transpeptidase), serum ferritin concentrations are significantly associated with insulin resistance in men and post-menopausal females, and the null association was observed in pre-menopausal females. Interestingly, an increased β-cell function associated with higher ferritin was observed in post-menopausal participants, but not in male participants. In conclusion, these results suggested that elevated serum ferritin levels were associated with surrogate measures of insulin resistance among the middle-aged and elderly male and post-menopausal women, but not in pre-menopausal women.

The Cut-off Values of Surrogate Measures for Insulin Sensitivity in a Healthy Population in Korea according to the Korean National Health and Nutrition Examination Survey (KNHANES) 2007-2010.

BackgroundThis study aimed to identify the gender-specific characteristics of the surrogate measures of insulin resistance and to establish valid cut-off values for metabolic abnormalities in a representative sample in Korea.MethodsData were collected from the datasets of the Korean National Health and Nutrition Examination Survey between 2007 and 2010. The total number of eligible participants was 10,997. We used three measures of insulin resistance: the homeostasis model assessment-insulin resistance (HOMA-IR), McAuley index, and triglyceride and glucose (TyG) index. The estimated cut-off values were determined using the highest score of the Youden index.ResultsThe area under the curve (AUC) of the HOMA-IR, McAuley index, and TyG index were 0.737 (95% confidence interval [CI], 0.725–0.750), 0.861 (95% CI, 0.853–0.870), and 0.877 (95% CI, 0.868–0.885), respectively. The cut-off values of the HOMA-IR were 2.20 in men, 2.55 in premenopausal women, and 2.03 in postmenopausal women, and those of the McAuley index were 6.4 in men and 6.6 in premenopausal and postmenopausal women. For the TyG index, the cut-off values were 4.76 in men and 4.71 in premenopausal and postmenopausal women.ConclusionIn conclusion, the present study provides the valid cut-off values of the indirect surrogate measures of insulin sensitivity. These values may be used as reference for insulin sensitivity in a clinical setting and may provide a simple and supplementary method for identifying populations at risk of insulin resistance.

Wheat germ supplementation alleviates insulin resistance and cardiac mitochondrial dysfunction in an animal model of diet-induced obesity.

Obesity is strongly associated with insulin resistance (IR), along with mitochondrial dysfunction to metabolically active tissues and increased production of reactive O2 species (ROS). Foods rich in antioxidants such as wheat germ (WG), protect tissues from damage due to ROS and modulate some negative effects of obesity. This study examined the effects of WG supplementation on markers of IR, mitochondrial substrate metabolism and innate antioxidant markers in two metabolically active tissues (i.e. liver and heart) of C57BL/6 mice fed a high-fat-high-sucrose (HFS) diet. Male C57BL/6 mice, 6-week-old, were randomised into four dietary treatment groups (n 12 mice/group): control (C, 10 % fat kcal), C+10 % WG, HFS (60 % fat kcal) or HFS+10 % WG (HFS+WG). After 12 weeks of treatment, HFS+WG mice had significantly less visceral fat (-16 %, P=0·006) compared with the HFS group. WG significantly reduced serum insulin (P=0·009), the insulinotropic hormone, gastric inhibitory peptide (P=0·0003), and the surrogate measure of IR, homoeostatic model assessment of IR (P=0·006). HFS diet significantly elevated (45 %, P=0·02) cardiac complex 2 mitochondrial VO2, suggesting increased metabolic stress, whereas WG stabilised this effect to the level of control. Consequently, genes which mediate antioxidant defense and mitochondrial biogenesis (superoxide dismutase 2 (Sod2) and PPARγ coactivator 1-α (Pgc1a), respectively) were significantly reduced (P<0·05) in the heart of the HFS group, whereas WG supplementation tended to up-regulate both genes. WG significantly increased hepatic gene expression of Sod2 (P=0·048) but not Pgc1a. Together, these results showed that WG supplementation in HFS diet, reduced IR and improved cardiac mitochondrial metabolic functions.

Insulin resistance correlates with maculopathy and severity of retinopathy in young adults with Type 1 Diabetes Mellitus.

To assess the relationship between insulin resistance (IR), retinopathy and maculopathy in young adults with Type 1 diabetes mellitus. A cross-sectional study at a regional Australian tertiary hospital. Retinal pathology, assessed by colour fundus photography, was correlated with two surrogate measures of IR: estimated Glucose Disposal Rate (eGDR) and Insulin Sensitivity Score (ISS), where lower scores reflect greater IR. 107 patients were recruited, with mean age 24.7years, 53% male, and mean duration of disease 10.8years. Mean eGDR scores (5.6vs 8.0 p<0.001) and ISS (4.7vs 7.9, p<0.001) were lower in subjects having at least moderate non-proliferative diabetic retinopathy (NPDR; relative to nil/mild-NPDR). Similarly, mean eGDR (4.2vs 6.2, p=0.001) and ISS (3.8vs 6.1, p=0.003) were lower in patients with maculopathy. Multivariate logistic regression modelling was used to control for confounding. For retinopathy severity, a unit increase in eGDR or ISS (representing lower IR) was associated with a 50% decrease in odds of moderate-NPDR or worse (eGDR OR 0.5, 95%CI 0.32-0.77, p=0.002; ISS OR 0.49, 95%CI 0.29-0.84, p=0.01). A unit increase in eGDR or ISS was associated with a 46-56% decrease in odds of maculopathy (eGDR OR 0.54, 95%CI 0.37-0.81, p=0.003; ISS OR 0.44, 95%CI 0.22-0.88, p=0.02). IR correlates with more severe retinopathy in young adults with Type 1DM. This is the first description of a correlation between IR and maculopathy in Type 1DM, warranting further evaluation. Prospective studies examining whether reducing IR can improve microvascular complications are required.

Burned Adults Develop Profound Glucose Intolerance.

Metabolic alterations after burn injury have been well described in children; however, in adult patients, glucose metabolism and insulin sensitivity are essentially unknown. We sought to characterize metabolic alterations and insulin resistance after burn injury and determine their magnitude and persistence at discharge. Prospective, cohort study. Tertiary burn centre. Nondiabetic adults with an acute burn involving greater than or equal to 20% total body surface area. An oral glucose tolerance test was administered at discharge. Glucose, insulin, and C-peptide levels were measured to derive surrogate measures of insulin resistance and β-cell function, including quantitative insulin sensitivity check index, homeostasis model assessment of β-cell function, homeostasis model assessment of insulin sensitivity, homeostasis model assessment of insulin resistance, and the composite whole-body insulin sensitivity index. Patients were grouped according to the degree of glucose tolerance: normal glucose tolerance, impaired fasting glucose/impaired glucose tolerance, or diabetes. Forty-five adults, 44 ± 15 years old and with 38% ± 14% total body surface area burned, underwent an oral glucose tolerance test at discharge. Median quantitative insulin sensitivity check index (0.348 [0.332-0.375]) and median homeostasis model assessment of insulin resistance (1.13 [0.69-1.45]) were abnormal, indicating insulin resistance and impaired insulin production at discharge. Two-thirds of patients (n = 28) met criteria for impaired fasting glucose/impaired glucose tolerance or diabetes. We have demonstrated that burn-injured adults remain hyperglycemic, are insulin resistant, and express defects in insulin secretion at discharge. Patients with lower burn severity (total body surface area, 20-30%) express similar metabolic alterations as patients with larger burns (total body surface area, ≥ 30%). Glucose tolerance testing at discharge offers an opportunity for early identification of burn patients who may be at high risk of prediabetes and diabetes. Our findings demonstrated that two-thirds of burn patients had some degree of glucose intolerance. With this in mind, surveillance of glucose intolerance post discharge should be considered. As hyperglycemia and insulin resistance are associated with poor outcomes, studies should focus on how long these profound alterations persist.

Vitamin D Supplementation Does Not Impact Insulin Resistance in Black and White Children.

Vitamin D supplementation trials with diabetes-related outcomes have been conducted almost exclusively in adults and provide equivocal findings. The objective of this study was to determine the dose-response of vitamin D supplementation on fasting glucose, insulin, and a surrogate measure of insulin resistance in white and black children aged 9–13 years, who participated in the Georgia, Purdue, and Indiana University (or GAPI) trial: a 12-week multisite, randomized, triple-masked, dose-response, placebo-controlled vitamin D trial. Black and white children in the early stages of puberty (N = 323, 50% male, 51% black) were equally randomized to receive vitamin D3 (0, 400, 1000, 2000, or 4000 IU/day) for 12 weeks. Fasting serum 25-hydroxyvitamin D (25(OH)D), glucose and insulin were assessed at baseline and weeks 6 and 12. Homeostasis model assessment of insulin resistance was used as a surrogate measure of insulin resistance. Statistical analyses were conducted as intent-to-treat using a mixed effects model. Baseline serum 25(OH)D was inversely associated with insulin (r = −0.140, P = 0.017) and homeostasis model assessment of insulin resistance (r = −0.146, P = 0.012) after adjusting for race, sex, age, pubertal maturation, fat mass, and body mass index. Glucose, insulin, and insulin resistance increased (F > 5.79, P < .003) over the 12 weeks, despite vitamin D dose-dependent increases in serum 25(OH)D. Despite significant baseline inverse relationships between serum 25(OH)D and measures of insulin resistance, vitamin D supplementation had no impact on fasting glucose, insulin, or a surrogate measure of insulin resistance over 12 weeks in apparently healthy children.

Homeostatic model assessment of insulin resistance as a predictor of metabolic syndrome: Consequences of obesity in children and adolescents

BackgroundObesity and/or insulin resistance have gained increasing attention as the core manifestations of metabolic syndrome. ObjectiveTo evaluate insulin resistance according to homeostasis model assessment of insulin resistance index HOMA-IR in obese children and adolescents with or without metabolic syndrome at risk of type 2 diabetes mellitus. Design and subjects60 obese children and adolescents were recruited, metabolic syndrome was diagnosed according to the modified WHO criteria adapted for children and adolescents. Insulin resistance was calculated using the HOMA-IR. ResultsMetabolic syndrome (MS) was found in 42 subjects (70%), using modified WHO guidelines for diagnosing MS. On comparing MS-related parameters between the groups with (MS+) and without metabolic syndrome (MS−), median body mass index, waist circumference, waist/height ratio, and blood pressure, total cholesterol and triglyceride were significantly higher in the MS+group. Basal insulin level as well as HOMA-IR was also significantly different between MS+ and MS-groups. The presence of insulin resistance according to HOMA-IR was identified in 53% of obese children and adolescents. This HOMA-IR age and sex limit was exceeded by 70% children in the MS+group, but only by 43% children in the MS-group (p<0.001). HOMA-IR was positively correlated with the majority of anthropometric and biochemical parameters. The correlation was strongest with body mass index, waist circumference and diastolic blood pressure. ConclusionsHOMA-IR might be a reliable surrogate measure of insulin resistance and a strong predictor of type 2 diabetes in obese adolescents allowing the development of preventive measures and treatment when needed.

Sex differences in biomarkers associated with insulin resistance in obese adolescents: metabolomic profiling and principal components analysis.

Obesity and insulin resistance (IR) predispose to type 2 diabetes mellitus. Yet only half of obese adolescents have IR and far fewer progress to type 2 diabetes mellitus. We hypothesized that amino acid and fatty acid metabolites may serve as biomarkers or determinants of IR in obese teens. Fasting blood samples were analyzed by tandem mass spectrometry in 82 obese adolescents. A principal components analysis and multiple linear regression models were used to correlate metabolic components with surrogate measures of IR: homeostasis model assessment index of insulin resistance (HOMA-IR), adiponectin, and triglyceride (TG) to high-density lipoprotein (HDL) ratio. Branched-chain amino acid (BCAA) levels and products of BCAA catabolism were higher (P < .01) in males than females with comparable body mass index (BMI) z-score. In multivariate analyses, HOMA-IR in males correlated positively with BMI z-score and a metabolic signature containing BCAA, uric acid, and long-chain acylcarnitines and negatively with byproducts of complete fatty acid oxidation (R(2) = 0.659, P < .0001). In contrast, only BMI z-score correlated with HOMA-IR in females. Adiponectin correlated inversely with BCAA and uric acid (R(2) = 0.268, P = .0212) in males but not females. TG to HDL ratio correlated with BMI z-score and the BCAA signature in females but not males. BCAA levels and byproducts of BCAA catabolism are higher in obese teenage boys than girls of comparable BMI z-score. A metabolic signature comprising BCAA and uric acid correlates positively with HOMA-IR in males and TG to HDL ratio in females and inversely with adiponectin in males but not females. Likewise, byproducts of fatty acid oxidation associate inversely with HOMA-IR in males but not females. Our findings underscore the roles of sex differences in metabolic function and outcomes in pediatric obesity.

Insulin resistance increases before ventilator-associated pneumonia in euglycemic trauma patients.

Hyperglycemia caused by stress-induced insulin resistance is associated with both infection and mortality in critically injured patients. The onset of infection may increase stress-induced insulin resistance, leading to hyperglycemia. Hyperglycemia has been shown to precede the diagnosis of ventilator-associated pneumonia (VAP) in critically injured adults and has been suggested to have potential diagnostic importance. However, glycemic control (GC) protocols in critically ill patients limit the development of hyperglycemia despite increasing insulin resistance. Our computer-assisted GC protocol achieves excellent GC, limiting infection-related hyperglycemia while capturing prospectively all glucose values, insulin infusion rates, and the multiplier (M) used to calculate the insulin rate. We hypothesized that surrogate measures of insulin resistance, the insulin infusion rate and multiplier M, would increase prior to the clinical suspicion of VAP, even in euglycemic critically injured patients. All critically injured patients (2,656) on the computerized glycemic control protocol were included in the analysis and categorized by those developing VAP and those without pneumonia on days 3-10 of their intensive care unit (ICU) stay. Median blood glucose concentration (BG), insulin infusion rate (IDR), and multiplier (M) [Insulin Drip Rate=M*(BG-60)] were determined for VAP patients (n=329) and non-infected ventilated (NIV) patients (n=2,327) on each day of mechanical ventilation. The day of VAP diagnosis according to U.S. Centers for Disease Control and Prevention (CDC) criteria was defined as day zero and VAP patients matched with NIV patients according to ventilator day from -10 to +10. Comparisons were conducted using the Mann-Whitney U test. Baseline characteristics between VAP and NIV groups did not differ. Measures of insulin resistance increased from the time of injury in both groups. Patients with VAP had significantly greater change in both measures of insulin resistance, IDR and M, in the 48 hours preceding the diagnosis of VAP. These changes occurred despite the fact that the computer-assisted GC protocol achieved lower glucose values in VAP patients for the majority of study days. Measures of insulin resistance increase in the two days prior to the clinical suspicion of VAP for critically injured patients on the GC protocol. These changes occur despite the protocol maintaining euglycemia. This data suggests that markers of insulin resistance may provide clinically useful information in the early diagnosis of VAP.

Surrogate measures of insulin resistance: does one size fit all?

Insulin resistance and a relative deficiency in insulin secretion are the major pathophysiological features of impaired glucose tolerance and type 2 diabetes. Although the euglycaemic-hyperinsulinaemic clamp and the hyperglycaemic clamp are the 'gold standards', respectively, for measuring these metabolic defects, there has been an active search during the past few decades for simpler and less expensive surrogate measures of insulin resistance that can be applied more globally in epidemiological studies or large clinical trials. These surrogate markers primarily rely on plasma insulin and glucose levels measured either in the fasting state or after an oral glucose challenge. Although many of these surrogate measures correlate well with the clamp (with r values frequently as high as 0.60-0.70) within racially and ethnically homogeneous populations, it is not clear how well they can be used to compare insulin action across different groups. In this issue of Diabetologia, Ahuja et al (DOI: 10.1007/s00125-014-3414-6 ) have used these methods to compare insulin resistance in a white population in the USA with a Japanese population in Japan. The relative merits and drawbacks of applying these techniques in different populations are discussed.

Insulin resistance in Saudi postmenopausal women with and without metabolic syndrome and its association with vitamin D deficiency

BackgroundThere is increasing interest in the non-skeletal effects of vitamin D and the relationship between vitamin D deficiency and chronic conditions such as diabetes mellitus. We aimed to investigate the relationship between surrogate indices of insulin resistance (IR), and vitamin D deficiency/insufficiency in postmenopausal Saudi women with and without metabolic syndrome. MethodsThe study population consisted of 300 postmenopausal women aged 46–88 years enrolled consecutively from women attending the Outpatient Clinics of King Abdulaziz University Hospital. Demographic, anthropometric, and biochemical parameters were recorded. Data were analyzed for women with and without metabolic syndrome. ResultsAbdominal obesity, IR, and hypovitaminosis D were highly prevalent within our population sample. Of the components used to define metabolic syndrome; waist circumference, serum triglycerides (TG), high density lipoprotein-cholesterol, and fasting blood glucose (FBG) were significantly related with all surrogate measures of IR. Significant inverse correlations were found between serum vitamin D and serum TG, FBG, and diastolic blood pressure, within the study cohort. ConclusionsThese observations suggest that hypovitaminosis D may be associated with the risk of developing metabolic syndrome. Interrelationships between IR, metabolic syndrome, and hypovitaminosis D are of particular interest in Saudi population, given the high prevalence of these conditions in this region.

Fatty Acid Desaturase Gene Polymorphisms and Metabolic Measures in Schizophrenia and Bipolar Patients Taking Antipsychotics

Atypical antipsychotics have become a common therapeutic option in both schizophrenia and bipolar disorder. However, these medications come with a high risk of metabolic side effects, particularly dyslipidemia and insulin resistance. Therefore, identification of patients who are at increased risk for metabolic side effects is of great importance. The genetics of fatty acid metabolism is one area of research that may help identify such patients. Therefore, in this present study, we aimed to determine the effect of one commonly studied genetic polymorphism from both fatty acid desaturase 1 (FADS1) and FADS2 gene on a surrogate measure of insulin resistance and lipid levels in a metabolically high-risk population of patients largely exposed to atypical antipsychotics. This study used a cross-sectional design, fasting blood draws, and genetic analysis to investigate associations between polymorphisms, haplotypes, and metabolic measures. A total of 320 subjects with schizophrenia (n = 226) or bipolar disorder (n = 94) were included in this study. The mean age of the population was 42.5 years and 45% were male. A significant association between FADS1 and FADS2 haplotypes was found with insulin resistance while controlling for confounders. Further investigation is required to replicate this finding.

Surrogate Measures of Insulin Resistance in Middle-aged Non-diabetic Subjects

Abstract Objective: Insulin resistance has been shown to be a risk factor for type 2 diabetes and cardiovascular disease. The assessment of insulin sensitivity in the clinical practice, however, faces several difficulties. The study proposes to analyze surrogate measures of insulin resistance based on fasting insulin levels in central Romania, and check whether the diagnosis of the metabolic syndrome is an adequate strategy to identify middle-aged persons with reduced insulin sensitivity. Methods: Anthropometric measurements, metabolic profile, and surrogates measures of insulin sensitivity (GIR, HOMA, QUICKI, FIRI, Belfiore, Bennett, Raynaud, McAuley index) based on fasting insulin levels were assessed in 233 non-diabetic middle aged subjects. Results: Cutoff values, determined as the lowest quartile of insulin sensitivity for fasting insulin, HOMA, IRI (1/QUICKI), FIRI and Belfiore's, Bennett's, Raynaud's and McAuley's insulin sensitivity indices were 10.49 mU/L, 2.1, 3.01, 2.32, and 0.03, 1.34, 3.81, 6.29, 5.82. Components of the metabolic syndrome showed moderate but significant correlations with the surrogate measures of insulin resistance (r = 0.22-0.56, p &lt;0.05). HOMA-IR and McAuley indices were the best predictors of clustered cardiometabolic risk factors (AUC - 0.83, 0.81 and 0.82). The metabolic syndrome diagnosis performed well in identifying patients with reduced insulin sensitivity (McAuley 2: sensitivity - 0.78, specificity - 0.84). Conclusion: Fasting insulin derived insulin sensitivity indices may help the recognittion of insulin resistant states predicting cardiometabolic disorders. Actively looking for insulin resistance by these simple indices, or by diagnosing the metabolic syndrome, those at increased risk can be recognized

Urine C-peptide creatinine ratio can be used to assess insulin resistance and insulin production in people without diabetes: an observational study

ObjectivesThe current assessment of insulin resistance (IR) in epidemiology studies relies on the blood measurement of C-peptide or insulin. A urine C-peptide creatinine ratio (UCPCR) can be posted from home...

AB1098 Obesity and insulin resistance in fibromyalgia patients

BackgroundFibromyalgia is a chronic disorder of uncertain etiology characterized by widespread pain and reduced threshold to pressure and other stimuli. Scientific evidences show a relationship between fibromyalgia and obesity. Insulin...

Association between β2‐adrenoceptor (ADRB2) haplotypes and insulin resistance in PCOS

The aim of this study was to explore β2-adrenoceptor (ADRB2) haplotype associations with phenotypes and quantitative traits related to insulin resistance (IR) and the metabolic syndrome (MS) in a polycystic ovary syndrome (PCOS) population. A secondary purpose was to assess the association between ADRB2 haplotype and PCOS. Genetic polymorphism analysis. Cross-sectional case-control association study. Medical University Hospital and research laboratory. One hundred and sixty-five unrelated women with PCOS and 116 unrelated women without PCOS (control sample). Clinical and biochemical measurements, and ADRB2 genotyping in PCOS patients and control subjects. ADRB2 haplotypes (comprising rs1042711, rs1801704, rs1042713 and rs1042714 in that order), genotyping and statistical analysis to evaluate associations with continuous variables and traits related to IR and MS in a PCOS population. Associations between ADRB2 haplotypes and PCOS were also assessed. We observed an age-adjusted association between ADRB2 haplotype CCGG and lower insulin (P = 0·018) and HOMA (P = 0·008) in the PCOS sample. Interestingly, the expected differences in surrogate measures of IR between cases and controls were not significant in CCGG/CCGG carriers. In the case-control study, genotype CCGG/CCGG was associated with a 14% decrease in PCOS risk (P = 0·043), taking into account confounding variables. Haplotype I (CCGG) has a protective role for IR and MS in PCOS.

The effect of different doses of vitamin D supplementation on insulin resistance during pregnancy

Low serum vitamin D levels are correlated with insulin resistance during pregnancy. We have assessed the effects of different doses of vitamin D on insulin resistance during pregnancy. A randomized clinical trial was done on 120 women with a gestational age of less than 12 weeks. The women were divided into three groups randomly. Group A received 200 IU vitamin D daily, group B 50 000 IU vitamin D monthly and group C 50 000 IU vitamin D every 2 weeks from 12 weeks of pregnancy until delivery. The serum levels of fasting blood sugar (FBS), insulin, calcium and 25-hydroxyvitamin D were measured before and after intervention. We used the homeostatic model assessment of insulin resistance (HOMA-IR) as a surrogate measure of insulin resistance. The mean ± standard deviation of serum 25-hydroxyvitamin D increased in group C from 7.3 ± 5.9 to 34.1 ± 11.5 ng/ml and in group B it increased from 7.3 ± 5.3 to 27.23 ± 10.7 ng/ml, but the level of vitamin D in group A increased from 8.3 ± 7.8 to 17.7 ± 9.3 ng/ml (p < 0.001). The mean differences of insulin and HOMA-IR before and after intervention in groups A and C were significant (p = 0.01, p = 0.02). This study has shown that supplementation of pregnant women with 50 000 IU vitamin D every 2 weeks improved insulin resistance significantly.