Serum phospholipid omega-3 polyunsaturated fatty acids and insulin resistance in type 2 diabetes mellitus and non-alcoholic fatty liver disease

AimsTo investigate the relationship between serum phospholipid omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD).Methods51 patients with T2DM and NAFLD (T2DM + NAFLD group), 50 with T2DM alone (T2DM group), 45 with NAFLD alone (NAFLD group), and 42 healthy control subjects (NC group) were studied. Serum ω-3 PUFA profiles were analyzed by gas chromatography, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and serum lipid concentrations were measured. Insulin resistance was assessed by the homeostasis model assessment method (HOMA-IR).ResultsHOMA-IR levels were higher in the T2DM + NAFLD group than in the T2DM, NAFLD and NC groups (p < 0.05), as were ALT, AST, GGT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) concentrations (p < 0.05). Conversely, serum ω-3 PUFA levels were significantly lower in the T2DM + NAFLD group than in the other groups (p < 0.05). The ω-3 PUFA level was negatively correlated with HOMA-IR, TC, LDL-C and TG.ConclusionsSerum phospholipid ω-3 PUFA levels were significantly decreased in patients with T2DM and NAFLD, and were negatively related with insulin resistance. Thus, reduced ω-3 PUFAs may play an important role in the development of T2DM and NAFLD.     

Gender-specific differences in clinical and metabolic variables associated with NAFLD in a Mexican pediatric population

Introduction and ObjectivesNon-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and it is more prevalent in Hispanic males. The gender differences can be explained by body fat distribution, lifestyle, or sex hormone metabolism. We evaluated anthropometric and metabolic differences by gender in children with and without NAFLD.MethodsWe included 194 participants (eutrophic, overweight, and individuals with obesity). The presence of NAFLD was determined using ultrasonography, and we evaluated the association between this disease with metabolic and anthropometric variables by gender.ResultsThe mean age was 10.64 ± 2.54 years. The frequency of NAFLD in boys was 24.51% and in girls was 11.96% (OR = 2.39; 95%CI = 1.10–5.19; p = 0.025). For girls, NAFLD was significantly associated with triglycerides (p = 0.012), homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.048), and the visceral adiposity index (VAI) (p = 0.024). The variables related to NAFLD in a gender-specific manner were body mass index (BMI) (p = 0.001), waist circumference (WC) (p < 0.001), HDL cholesterol (p = 0.021), alanine aminotransferase (ALT) (p < 0.001), and aspartate aminotransferase (AST) (p = 0.002).ConclusionsIn our study NAFLD is more frequent in boys, only ALT, and no other clinical or metabolic variables, were associated with NAFLD in these patients. HOMA-IR, VAI, triglyceride levels, and ALT were associated with NAFLD only in girls. The ALT cut-off points for the development of NAFLD in our study were 28.5 U/L in females and 27.5 U/L in males. Our findings showed that NAFLD should be intentionally screened in patients with obesity, particularly in boys.     

Is HOMA-IR a potential screening test for non-alcoholic fatty liver disease in adults with type 2 diabetes?

BackgroundNon-alcoholic fatty liver disease (NAFLD) is the commonest hepatic disease in many parts of the World, with particularly high prevalence in patients with type 2 diabetes (T2DM). However, a good screening test for NAFLD in T2DM has not been established. Insulin resistance (IR) has been associated with NAFLD, and homeostatic model assessment of insulin resistance (HOMA-IR), a good proxy for IR, may represent an affordable predictive test which could be easily applied in routine clinical practice. We aimed to evaluate the diagnostic accuracy of HOMA-IR for NAFLD in T2DM and sought to estimate an optimal cut-off value for discriminating NAFLD from non-NAFLD cases.MethodsWe conducted a retrospective analysis of 56 well-controlled patients with T2DM (HbAc1 < 7%, on oral anti-diabetic and/or glucagon-like peptide-1 agonist treatment), who had at least one glucose and insulin level determined, and at least one hepatic imaging test (ultrasonography or computed tomography scanning).ResultsThe prevalence of NAFLD was 73.2% (95% CI: 59.7–84.2) in our population. An association between HOMA-IR and NAFLD was found (OR 1.5; 95% CI: 1.03–2.1; p = 0.033), independently of transaminases, fat percentage, BMI and triglyceride levels. The AUROC curve of HOMA-IR for identifying NAFLD was 80.7% (95% CI: 68.9–92.5). A value of HOMA-IR of 4.5 was estimated to be an optimal threshold for discriminating NAFLD from non-NAFLD cases.ConclusionHOMA-IR is independently associated with the presence of NAFLD in adults with T2DM, and might potentially be applied in clinical practice as a screen for this condition.     

Assessment of insulin resistance using surrogate markers in patients of metabolic syndrome

BackgroundInsulin resistance is defined as situation where there is insufficient biological or metabolic response to normal plasma levels of insulin. For precise quantification of insulin sensitivity, the euglycemic hyperinsulinemic clamp may be used, but it is expensive, invasive and used mainly in research settings. HOMA-IR (Homeostasis Model Assessment-Insulin Resistance) and ISI 0,120 (Insulin Sensitivity Index) are indirect markers of insulin resistance. The present study evaluated the usefulness of the surrogate markers for evaluation of Insulin resistance in clinical settings.MethodThis study was carried out on 120 subjects. Of these, 60 subjects presenting with two or more features of metabolic syndrome (Hypertension, Obesity, Dyslipidemia, altered glucose tolerance) were included in the study group. Sixty age and sex matched healthy controls were selected with normal Body mass index. All the subjects underwent a standard Oral Glucose Tolerance Test. Plasma glucose and serum insulin were estimated using Glucose oxidase and ELISA principle respectively. HOMA-IR and ISI 0,120 were calculated using relevant formulae.ResultThe HOMA-IR values were significantly raised in suspected Insulin resistant subjects (6.74 ± 1.24) as compared to healthy controls (0.82 ± 0.017) (p = 0.001). ISI 01,20 was significantly low in insulin resistant subjects (3.13 ± 0.17) as compared to controls (20.60 ± 0.37) (p < 0.001). Insulin sensitivity index showed a significant negative correlation with HOMA-IR. A significant negative correlation was observed between serum cholesterol, serum LDL-cholesterol and ISI 0,120 indicating that dyslipidemia in metabolic syndrome may result from a decrease in Insulin sensitivity.ConclusionHOMA-IR and ISI 0,120 are simple, convenient and sensitive estimates of insulin resistance adaptable for use in clinical practice as well as large-scale epidemiological studies.     

Association between vascular inflammation and non-alcoholic fatty liver disease: Analysis by 18F-fluorodeoxyglucose positron emission tomography

BackgroundGrowing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease as well as metabolic syndrome. FDG-PET is a novel imaging technique that detects vascular inflammation, which may reflect rupture-prone vulnerable atherosclerotic plaques.MethodsVascular inflammation was measured as the maximum target-to-background ratio (maxTBR), along with various cardiometabolic risk factors in 51 subjects with NAFLD, and compared with 100 age- and gender-matched subjects without NAFLD. The liver attenuation index (LAI), which was measured using computed tomography, was used as a parameter for the diagnosis of NAFLD.ResultsAfter adjusting for age and sex, both maxTBR and LAI values were associated with several cardiometabolic risk parameters. Furthermore, there was a significant inter-relationship between LAI and maxTBR values (r = − 0.227, P = 0.005). Individuals with NAFLD had higher maxTBR values than those without NAFLD (P = 0.026), although their carotid intima–media thickness (CIMT) values did not differ. The proportion of subjects with NAFLD showed a step-wise increment following the tertiles of maxTBR values (P for trend = 0.015). In multiple logistic regression analysis, maxTBR tertiles were independently associated with NAFLD after adjusting for age, gender, systolic blood pressure, triglycerides, HDL-cholesterol, glucose, BUN, creatinine and homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.030). However, their relationship was attenuated after further adjustment for waist circumference or high sensitive C-reactive protein.ConclusionPatients with NAFLD have an increased risk for vascular inflammation as measured via FDG-PET/CT even without difference in CIMT. (Clinical trials No. NCT01958411, http://www.clinicaltrials.gov/)     

Association of nonalcoholic fatty liver disease with metabolic syndrome in Indian population

BackgroundNonalcoholic fatty liver disease (NAFLD), a common cause of cryptogenic cirrhosis is often associated with metabolic syndrome (MS) in the West. However, its association with MS in the Indian population is not well studied.AimsTo evaluate the association NAFLD with MS using the modified ATP-III criteria.Patients and methodsSeventy-six (62 men, mean age 40.05 ± 11.4 years, range 18–66) apparently healthy subjects with fatty liver and histological evidence of NAFLD; with (64.5%) or without raised ALT, and 100 healthy controls were included in the study. The anthropometric measurements, metabolic parameters, tests of liver function and liver histology were studied.ResultsTwenty-one percent of the patients compared to 8% controls (p < 0.01) had associated MS; according to ATP-III criteria while 42 and 12% were affected when the modified ATP-III criteria were used. About 35% of non-diabetic patients were insulin resistant with homeostatic model assessment-insulin resistance (HOMA-IR) cut-off set at 3. In patients, compared to controls, the mean BMI (25.2 vs. 22.7, p < 0.01) and waist circumferences (92.9 cm vs. 80.8 cm, p < 0.01) were higher. Seventy-nine percent of the patients and 44% of the controls were over weight. Stage 1 fibrosis was seen in 30 (39.5%), stage 2 in 10 (13.2%), stage 3 in 6 (7.9%) and stage 4 in 13 (17%) patients.ConclusionsInsulin resistance and obesity are associated in a proportion of Indian patients with NAFLD. However, the association with MS as defined by ATP-III in Indian patients is not strong compared to the West. It is likely that pathogenetic mechanisms unrelated to MS underlie development of NAFLD in a proportion of Indian patients.     

Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: An updated systematic review of randomized controlled trials

AimThere are no approved drugs for the treatment of non-alcoholic fatty liver disease (NAFLD). However, many randomized controlled trials (RCT) have examined the effect of anti-hyperglycaemic agents on NAFLD in patients with and without type 2 diabetes mellitus (T2DM), since both T2DM and insulin resistance are closely linked to this burdensome liver disease.MethodsWe systematically searched publication databases using predefined keywords to identify head-to-head or placebo-controlled RCTs (published until September 30, 2019) of NAFLD individuals testing the efficacy of anti-hyperglycaemic drugs to specifically treat NAFLD or non-alcoholic steatohepatitis (NASH). Outcomes of interest included changes in serum liver enzyme levels, liver fat, liver fibrosis, or histologic resolution of NASH.ResultsWe included 29 RCTs involving a total of 2,617 individuals (∼45% had T2DM) that have used metformin (n = 6 studies), glitazones (n = 8 studies), glucagon-like peptide-1 receptor agonists (n = 6 studies), dipeptidyl peptidase-4 inhibitors (n = 4 studies) or sodium-glucose cotransporter-2 inhibitors (n = 7 studies) to treat NAFLD. Although most anti-hyperglycaemic drugs improved serum liver enzyme levels, only glitazones (especially pioglitazone) and liraglutide showed an improvement of histologic features of NAFLD, with a mild beneficial effect also on liver fibrosis for pioglitazone only.ConclusionRCT evidence supports the efficacy of some anti-hyperglycaemic agents (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with pioglitazone may warrant caution. Further well-designed RCTs are needed to better characterize the efficacy and safety of monotherapy and combination therapy with anti-hyperglycaemic agents in patients with NAFLD.     

Effect of cigarette smoking on insulin resistance risk

ObjectivesSmoking is one of the main risk factors for cardiovascular disease (CVD). The mechanism(s) of the effects of smoking on CVD are not clearly understood; however, a number of atherogenic characteristics, such as insulin resistance have been reported. We aim to investigate the effects of cigarette smoking on insulin resistance and to determine the correlation between this parameter with smoking status characteristics.Study designThis study was conducted on 138 non-smokers and 162 smokers aged respectively 35.6 ± 16.0 and 38.5 ± 21.9 years. All subjects are not diabetic.MethodsFasting glucose was determined by enzymatic methods and insulin by chemiluminescence method. Insulin resistance (IR) was estimated using the Homeostasis Model of Assessment equation: HOMA-IR = [fasting insulin (mU/L) × fasting glucose (mmol/L)]/22.5. IR was defined as the upper quartile of HOMA-IR. Values above 2.5 were taken as abnormal and reflect insulin resistance.ResultsCompared to non-smokers, smokers had significantly higher levels of fasting glucose, fasting insulin and HOMA-IR index. These associations remained significant after adjustment for confounding factors (age, gender, BMI and alcohol consumption). A statistically significant association was noted between the smoking status parameters, including both the number of cigarettes smoked/day and the duration of smoking, and fasting insulin levels as well for HOMA-IR index. Among smokers, we noted a positive correlation between HOMA-IR index and both plasma thiocyanates and urinary cotinine.ConclusionOur results show that smokers have a high risk to developing an insulin resistance and hyperinsulinemia, compared with a matched group of non-smokers, and may help to explain the high risk of cardiovascular diseases in smokers.     

Association of insulin resistance,insulin and leptin levels with coronary in-stent restenosis

BackgroundIn-stent restenosis remains the major limitation of coronary stent implantation. Leptin is a hormone strongly related to insulin resistance (IR). Moreover, insulin resistance and hyperinsulinemia are common in patients with coronary heart disease (CHD), each of the previous metabolic and hormonal factors might be involved in restenosis after stent implantation.ObjectiveThis study was planned to evaluate the relationship between insulin resistance, insulin, leptin levels and coronary in-stent restenosis after coronary stent implantation in non-diabetic patients with CHD and to determine their value in prediction of restenosis.Patients and methodsThe study included 48 non-diabetic CHD patients with previous successful coronary stent implantation. They were divided into two groups according to the presence of in-stent restenosis on follow-up coronary angiography (6–9 months after stent implantation). The first group was CHD patients with in-stent restenosis which included 20 patients, the second group was CHD patients without restenosis which included 28 patients. All patients were subjected to complete clinical examination including determination of body mass index (BMI), waist to hip ratio (WHR) and laboratory investigations including fasting plasma glucose (FPG), fasting plasma insulin (FP insulin), lipid profile (total cholesterol, HDL-C, LDL-C, TG), glycoselated hemoglobin (HbA1c), plasma leptin, estimation of homeostasis model assessment of IR (HOMA-IR). All subjects were submitted to OGTT with estimation of 2-h post-prandial glucose (2-hPP glucose) and sum post-prandial insulin levels (sum PP insulin). Follow-up coronary angiography was done for all patients with the estimation of minimal luminal diameter (MLD), diameter stenosis % and late lumen loss.ResultsThere was highly significant increase in each of FP insulin, sum PP insulin, HOMA-IR, leptin, diameter stenosis % and late lumen loss (P < 0.001) and a highly significant decrease of MLD (P < 0.001) in CHD patients with in-stent restenosis when compared to CHD patients without in-stent restenosis. MLD is negatively correlated to each of FP insulin (r = −0.49, P < 0.001), sum PP insulin (r = −0.60, P < 0.001) HOMA-IR (r = −0.63, P < 0.001) and leptin (r = −0.55, P < 0.001) while late lumen loss was positively correlated to each of FP insulin (r = 0.98, P < 0.001), sum PP insulin (r = 0.70, P < 0.001), HOMA-IR (r = 0.67, P < 0.001) and leptin (r = 0.72, P < 0.001). Multiple regression analysis revealed that each of FP insulin, sum PP insulin, HOMA-IR and leptin can be considered an independent predictor of in-stent restenosis (P < 0.001).ConclusionOur study revealed that insulin resistance, fasting and post-prandial hyperinsulinemia and hyperliptinemia are considered predictors of coronary in-stent restenosis. Evaluation of HOMA-IR, insulin levels after standard OGTT and leptin levels are important tools in an attempt to recognize subjects at risk of early restenosis among non-diabetic, CHD patients undergoing percutaneous coronary revascularization and stent implantation.     

Associations between hemoglobin concentrations and the development of incidental metabolic syndrome or nonalcoholic fatty liver disease

AimsHemoglobin (Hb) is known to be associated with both nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS). We evaluated the relationship between serum Hb levels and the development of MS or NAFLD.MethodsA retrospective cohort study was conducted. We recruited participants who underwent abdominal ultrasonography and blood samplings in both 2005 and 2010.ResultsGraded independent relationships were observed between higher Hb levels and the incidence of MS and NAFLD. After adjusting for age, body mass index, and fasting glucose, high-density lipoprotein cholesterol and triglyceride levels, the risk of developing MS was significantly higher according to the Hb quartiles in men (P for trend = 0.027). The adjusted odds ratio (OR) and 95% confidence intervals (CIs) for the highest Hb quartile was 1.81 (1.06–3.10) for women and 1.43 (1.00–2.05) for men. The risk of developing NAFLD was also significantly higher according to the Hb quartiles in men (P for trend = 0.03). The adjusted OR and 95% CI for the highest Hb quartile was 1.18 (0.73–1.91) in women and 1.76 (1.16–2.66) in men.ConclusionsThe risk of developing either MS or NAFLD was significantly associated with serum Hb levels in men. These findings have implications in the clinical availability of serum Hb as a predictor of MS and NAFLD.     

Real-life comparison of DPP4-inhibitors with conventional oral antidiabetics as add-on therapy to metformin in elderly patients with type 2 diabetes: The HYPOCRAS study

AimDespite half of all type 2 diabetes mellitus (T2DM) patients being over 65 and treatment being complicated by an elevated risk of iatrogenic hypoglycaemia, information about antidiabetic treatment is scarce in this age group. This prospective observational study compares DPP4-inhibitors (DPP4-i) with conventional oral antidiabetic drugs (COAD) in the real-life treatment of elderly patients with T2DM uncontrolled on metformin alone.MethodsTwo treatment cohorts (DPP4-i and COAD, constituted on the basis of the GP decision of add-on therapy at the 1st visit) were compared after 6 months. The primary objective was to assess the incidence of hypoglycaemic episodes in relationship with glycaemic control assessed by HbA_1c level.ResultsDemographics and disease history were comparable between the two cohorts (DPP4-i, n = 931 and COAD, n = 257) at baseline. The incidence of hypoglycaemia/severe hypoglycaemia was significantly higher over 6 months in the COAD cohort (20.1%/2.4% vs. 6.4%/0.1%; P < 0.001) whereas similar improvements were observed in glycaemic control with HbA_1c down from 7.9% to 7.0% (COAD) and 6.9% (DPP4-i). The 7% target was reached without hypoglycaemia in more patients in the DPP4-i than in COAD cohort (59.7% vs. 45.5%; P < 0.001). Patients in both cohorts who experienced hypoglycaemia more frequently had a pre-existing diabetic complication. The COAD was more likely to be discontinued (6.6% vs. 1.6%; P < 0.001).ConclusionThis large cohort study of elderly T2DM patients in France shows that the incidence of hypoglycaemia was three times higher in patients prescribed a COAD versus a DPP4-i after 6 months while both treatments induced satisfactory glycaemic control.     

Serum adipokine profile in Indian men with nonalcoholic steatohepatitis: Serum adiponectin is paradoxically decreased in lean vs. obese patients

BackgroundAsian Indians are known to be more insulin resistant for the same degree of weight gain. It is therefore likely that the adipokine profile in nonalcoholic fatty liver disease (NAFLD) in Asian Indian population could be different from the Western subjects.AimsTo study the serum adiponectin, resistin, leptin and TNF-α profile in NAFLD and cryptogenic cirrhosis patients.Subjects and methodsBody mass indices, insulin resistance and serum adipokine levels were studied in 56 patients; 10 with fatty liver, 30 with nonalcoholic steatohepatitis (NASH) and 16 with cryptogenic cirrhosis. Eighteen healthy controls were also included.ResultsPatients in general were obese compared to controls (mean BMI 26.9 ± 4.5 vs. 22.6 ± 2.5, respectively, p < 0.0001). In patients with NASH, adiponectin levels were lower than controls (5.4 ± 3 μg/ml vs.7.2 ± 2.9 μg/ml, p = 0.037). Insulin Resistance as assessed by homeostasis model assessment (HOMA) was higher in obese than lean, NAFLD patients (HOMA IR obese, median = 2.8, range = 0.8–16.3 and lean: median = 1.05, range = 0.51–2.75, p = 0.003). Lean NAFLD patients had adiponectin levels lower than obese patients (3 ± 1 μg/ml vs.6.7 ± 3.8 μg/ml respectively, p = 0.003). Serum resistin levels were higher in NAFLD patients (3.7 ± 3 ng/ml) than controls (2.1 ± 1.7 ng/ml, p = 0.007). This difference was significant even when cirrhotic patients were excluded (3.4 ± 2.7 ng/ml, p = 0.036). Serum leptin levels were raised in cryptogentic cirrhosis compared to NASH (p = 0.03). All adipokines tested were raised in cirrhotic patients compared to NAFLD and controls.ConclusionsA significant reduction in serum adiponectin and increase in serum resistin levels were observed in NAFLD patients, more so in lean than obese NAFLD. This paradoxical decrease of serum adiponectin as well as low frequency of insulin resistance in lean NAFLD suggests a possible different etiology for this subset of patients.     

Plasma adiponectin levels are related to obesity,inflammation, blood lipids and insulin in type 2 diabetic and non-diabetic Trinidadians

AimsTo determine the relationship between plasma adiponectin levels and obesity, inflammation, blood lipids and insulin resistance in type 2 diabetics (T2DM) and non-diabetics in a patient population in Trinidad.MethodsA cohort study of a total of 126 type 2 diabetic (42 males and 84 females) and 140 (43 males and 97 females) non-diabetic public clinic attendees were assessed between December 2008 and July 2009. Along with clinical history and anthropometry, adiponectin, TNF-α, IL-6, CRP, lipid profile, glucose, and insulin were measured in fasting blood samples and insulin resistance (HOMA-IR) was calculated.ResultsDiabetics had higher (p < 0.05) glucose, insulin, HOMA-IR, triglycerides (TG), VLDL and systolic blood pressure than non-diabetics, but lower (p < 0.05) HDL and adiponectin levels. Adiponectin levels were lower (p < 0.05) in obese than in non-obese individuals regardless of diabetic status. There were significant gender differences in HDL, LDL and TG. Among non-obese persons, adiponectin correlated negatively with triglycerides (r = ?0.280; adiponectin), IL-6 (r = ?0.216; p < 0.005), HOMA-IR (r = ?0.373; p = 000) and positively correlated with HDL (r = 0.355; p = 0.000). Diabetic status (p = 0.025), TNF-α (p = 0.048) and BMI (p = 0.027) were identified as useful predictors of adiponectin by multiple linear regression methods. In addition binary logistic regression analysis found glucose (p = 0.001) and adiponectin (p = 0.047) to be useful indicators of type 2 diabetes.ConclusionsAdiponectin decreases with increasing adiposity and insulin resistance. Adiponectin and TNF-α appear to be related to differences in the insulin mediated glucose turnover.     

Effect of short-term intensive insulin therapy on the incretin response in early type 2 diabetes

AimsShort-term intensive insulin therapy (IIT) and gastric bypass surgery are both interventions that can improve beta-cell function, reduce insulin resistance and induce remission of type 2 diabetes. Whereas gastric bypass yields an enhanced glucagon-like peptide-1 (GLP-1) response that may contribute to its metabolic benefits, the effect of short-term IIT on the incretin response is unclear. Thus, we sought to evaluate the impact of IIT on GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion in early type 2 diabetes.MethodsIn this study, 63 patients (age 59 ± 8.3 years, baseline A1c 6.8 ± 0.7%, diabetes duration 3.0 ± 2.1 years) underwent 4 weeks of IIT (basal insulin detemir and pre-meal insulin aspart). GLP-1, GIP and glucagon responses were assessed by the area-under-the-curve (AUC) of these hormones on oral glucose tolerance tests at baseline and 1-day after the completion of therapy. Beta-cell function was assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2), with insulin resistance measured by Homeostasis Model Assessment (HOMA-IR).ResultsAs expected, comparing the post-therapy oral glucose tolerance test to that at baseline, IIT increased ISSI-2 (P = 0.02), decreased HOMA-IR (P < 0.001), and reduced AUC_glucagon (P < 0.001). Of note, however, IIT had no significant impact on AUC_GLP-1 (P = 0.24) and reduced AUC_GIP (P = 0.02).ConclusionDespite improving beta-cell function, insulin resistance and glucagonemia, short-term IIT does not change GLP-1 secretion and decreases the GIP response to an oral glucose challenge in early type 2 diabetes. Thus, the beneficial impact of this therapy on glucose homeostasis is not attributable to its effects on incretin secretion.     

The correlation of plasma omentin-1 with insulin resistance in non-obese polycystic ovary syndrome

ObjectivesAberrant circulating adipokines are considered to be related to the pathological mechanism of polycystic ovary syndrome (PCOS). This study aims to evaluate the relationship between plasma omentin-1 levels, metabolic and hormonal parameters in the setting of non-obese Chinese women with PCOS.Material and methodsThis was a case-controlled, cross-sectional study of 153 non-obese (BMI < 25 kg/m²) PCOS and 114 age-matched healthy non-obese control individuals. Levels of plasma omentin-1, fasting blood glucose, insulin and sexual hormones and ovary volume were analyzed in all subjects.ResultsPlasma omentin-1 levels of non-obese PCOS individuals were significantly lower than in healthy non-obese controls. Body Mass Index (BMI), homeostasis model of assessment for insulin resistance index (HOMA-IR), levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), LH/FSH ratio and ovary volume (OV) were significantly higher in subjects with PCOS than controls. In the HOMA-IR stratified subgroups, PCOS individuals with insulin resistance had lower omentin-1 than those without insulin resistance after BMI adjustment. Omentin-1 was negatively correlated with BMI, HOMA-IR and fasting insulin. Multiple linear regressions revealed that BMI contributed to omentin-1 levels. Ovary volume was negatively correlated to HOMA-IR but had no correlation with omentin-1.ConclusionsPlasma omentin-1 concentrations were decreased in the non-obese PCOS group. Insulin resistance could further decrease plasma omentin-1 in non-obese individuals with PCOS independent of BMI status.     

Serum Uric Acid concentration is associated with insulin resistance and impaired insulin secretion in adults at risk for Type 2 Diabetes

AimsInsulin resistance (IR) predisposes to type 2 diabetes mellitus (T2DM). Although previous studies have associated serum uric acid concentration with IR in T2DM, its association with impaired insulin secretion and beta-cell dysfunction in subjects at risk for developing T2DM remains uncertain. Thus, we aimed to analyze the association of serum uric acid concentration with IR using surrogate insulin resistance/secretion and beta-cell function indices in subjects at risk for developing T2DM.MethodsThis is a cross-sectional study that included 354 subjects who underwent an oral glucose tolerance test who had at least two risk factors for T2DM without any chronic disease.ResultsParticipants were 51 ± 8 years old, 72.2% were women, had a mean body mass index of 29.9 ± 6.5 kg/m² and mean serum uric acid concentration of 5.7 ± 1.3 mg/dL. HOMA-IR, first-phase insulin secretion (S1Ph_OGTT), second-phase insulin secretion (S2Ph_OGTT), Matsuda and disposition indices were significantly correlated with serum uric acid concentrations (r = 0.239, r = 0.225, r = 0.201, r = ?0.287, r = ?0.208; respectively). After multiple linear regression analysis, serum uric acid concentration was independently associated with HOMA-IR (β = 0.283), HOMA-B (β = 0.185), S1Ph_OGTT (β = 0.203), S2Ph_OGTT (β = 0.186), and Matsuda Index (β = ?0.322). A serum uric acid concentration of 5.5 mg/dL had the best sensitivity/sensibility to identify subjects with IR (HOMA-IR ≥2.5).ConclusionsSerum uric acid concentration is significantly associated with IR and impaired insulin secretion, but not with beta-cell dysfunction, in subjects at risk for developing T2DM.     

High prevalence of apolipoprotein B dyslipoproteinemias in non-alcoholic fatty liver disease: The lifelines cohort study

ObjectiveCardiovascular disease (CVD) is a major adverse consequence of non-alcoholic fatty liver disease (NAFLD). The association of NAFLD with various apolipoprotein B (apoB) dyslipoproteinemias is unclear. We determined the prevalence of specific apoB dyslipoproteinemias in subjects with suspected NAFLD.MethodsThis study was conducted among 22,865 fasting adults living in the northern part of the Netherlands (Lifelines Cohort Study). Six apoB dyslipoproteinemias were defined using an algorithm derived from apoB, total cholesterol and triglycerides. NAFLD was defined as Fatty Liver Index (FLI) ≥ 60. Advanced hepatic fibrosis was defined as NAFLD fibrosis score (NFS) ≥ 0.676.Results4790 participants (20.9%) had an FLI ≥ 60. NAFLD subjects were older, more likely to be men, more obese and more often had diabetes and metabolic syndrome (P < 0.001 for each). Among NAFLD subjects, any apoB dyslipoproteinemia was present in 61.5% vs. 16.5% in subjects without NAFLD (P < 0.001). Elevated chylomicrons were not observed in NAFLD. In univariate analysis, NAFLD was associated with a higher prevalence of each apoB dyslipoproteinemia vs. subjects with an FLI < 60 (P < 0.001), except for low density lipoprotein (LDL) dyslipoproteinemia. Additionally, each apoB dyslipoproteinemia was independently associated with NAFLD in age- and sex-adjusted logistic regression analysis, including the apoB dyslipoproteinemias together (P < 0.001). The prevalence of apoB dyslipoproteinemias was not altered in subjects with NFS ≥ 0.676.ConclusionsNAFLD rather than advanced hepatic fibrosis is independently associated with increased prevalence of chylomicrons + very low-density lipoproteins (VLDL) remnants, VLDL, LDL and VLDL + LDL dyslipoproteinemias. ApoB dyslipoproteinemias may contribute to increased CVD risk associated with NAFLD.     

Defining a cutoff point for vitamin D deficiency based on insulin resistance in children

BackgroundVitamin D deficiency is a common worldwide problem. Low levels of serum 25-hydroxy vitamin D [25(OH)D], as a marker of vitamin D deficiency, have been linked to a wide field of health problems, including metabolic diseases such as insulin resistance, type 1 and type 2 DM. There is no universal definition for cutoff value of vitamin D deficiency and it seems that it varies in different populations.ObjectiveMost previous studies have used a start rise of PTH as a criteria to detect threshold of serum 25(OH)D, However, the aim of this study was to determine a cutoff point of serum 25(OH)D for vitamin D deficiency based on HOMA-IR.Materials and methodsTwo hundred and ninety seven healthy children (aged 7–11 years) were enrolled. Serum 25(OH)D and PTH were measured and HOMA-IR was calculated. The ROC curve was utilized to obtain a cutoff of vitamin D deficiency based on HOMA-IR.Results25(OH)D concentrations were inversely correlated with HOMA-IR levels (Spearman's r = ?0.14, p = 0.016). Serum 25(OH)D cutoff point was 11.6 ng/mL (29 nmol/L) in relation with HOMA-IR >2.1. By using this cutoff value, the prevalence of vitamin D deficiency was 43.4% in this study population of healthy children.ConclusionWe found that serum 25(OH)D levels are inversely associated with insulin resistance. These results suggest that in MetS patients it may benefit to determine cutoff value of 25(OH)D levels based on HOMA-IR.     

Continuous positive airway pressure and diabetes risk in sleep apnea patients: A systemic review and meta-analysis

BackgroundThe study assessed the effect of continuous positive airway pressure (CPAP) therapy on the risk of developing type 2 diabetes by evaluating change in the homeostasis model assessment of insulin resistance (HOMA-IR) fasting blood glucose (FBG) and fasting insulin following CPAP treatment in non-diabetic patients and pre-diabetic with obstructive sleep apnea (OSA).MethodsMedline, PubMed, Cochrane, and EMBASE databases were searched until August 24, 2015. The analysis included randomized controlled trials (RCTs), two arm prospective studies, cohort studies, and retrospective studies. The primary outcome measure was change of HOMA-IR in pre-diabetic patients receiving CPAP treatment.ResultsTwenty-three studies were included with 965 patients who had OSA. Nineteen studies were prospective studies and four were RCTs. CPAP therapy resulted in a significant reduction in the pooled standard difference in means of HOMA-IR (− 0.442, P = 0.001) from baseline levels compared with the control group. Change in FBG and fasting insulin from baseline levels was similar for the CPAP and control groups. For RCT studies (n = 4), there was no difference in change in HOMA-IR or FBG levels from baseline between CPAP and control groups. The combined effect of RCTs showed that CPAP was associated with a significant reduction in change from baseline in fasting insulin than the control group (standardized diff. in means between groups = − 0.479, P value = 0.003).ConclusionThese findings support the use of CPAP in non-diabetic and pre-diabetic patients with OSA to reduce change of HOMA-IR and possibly reduce the risk of developing type 2 diabetes in this patient population.