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Aims Endothelial dysfunction and heart failure are associated, but no prospective studies demonstrated that impaired endothelium‐dependent vasodilation predicts incident heart failure. We designed this study to test whether endothelial dysfunction is associated with incident heart failure in a group of hypertensives. Methods and results We enrolled 735 White never‐treated hypertensive outpatients free from heart failure, diabetes, chronic kidney disease, and previous cardiovascular events. Endothelium‐dependent vasodilation was investigated by intra‐arterial infusion of acetylcholine, and laboratory determinations were obtained by standard procedures. During the follow‐up [median 114 months (range 26–206)], there were 208 new cases of heart failure (3.1 events/100 patient‐years). Dividing the study population in progressors and non‐progressors, we observed that progressors were older, showed a higher prevalence of being female, and had a higher baseline heart rate, glucose, insulin, Homeostatic Model Assessment (HOMA), creatinine, and high‐sensitivity C‐reactive protein (hs‐CRP) mean values, while estimated glomerular filtration rate and maximal acetylcholine‐stimulated forearm blood flow were lower. In the multiple Cox regression analysis, female gender [hazard ratio (HR) = 1.454, 95% CI = 1.067–1.981], fasting glucose (HR = 1.186, 95% CI = 1.038–1.357), hs‐CRP (HR = 1.162, 95% CI = 1.072–1.259), HOMA (HR = 1.124, 95% CI = 1.037–1.219), acetylcholine‐stimulated forearm blood flow (HR = 0.779, 95% CI = 0.695–0.874), and estimated glomerular filtration rate (HR = 0.767, 95% CI = 0.693–0.849) maintained an independent association with the outcome. Successively, testing the interaction between forearm blood flow and hs‐CRP, we observed that patients who have hs‐CRP values above the median and forearm blood flow under the median show a higher risk of developing heart failure (HR = 7.699, 95% CI = 4.407–13.451). Conclusions The present data demonstrate that an impaired endothelium‐dependent vasodilation and hs‐CRP predict development of incident heart failure in hypertensives.

BACKGROUND: High sterol regulatory binding protein 1c (SREBP-1c) gene expression increases triglyceride synthesis, which induces insulin resistance. Short-chain fatty acids (SCFAs) from fiber fermentation and beta carotene may inhibit SREBP-1c gene expression. AIM: The aim of this study was to evaluate the high fiber and beta carotene diet on improving insulin resistance in hypertriglyceridemia rats. METHODS: A total of 25 Wistar male rats were divided into five groups: (1) Normal control (NC); (2) hypertriglyceridemia control (HC); (3) hypertriglyceridemia rats with treatment 1 (HT1); (4) hypertriglyceridemia rats with treatment 2 (HT2); and (5) hypertriglyceridemia rats with treatment 1 (HT3). The HT1, HT2, and HT3 received fiber 1.0 g; 2.0 g; and 3.1 g and beta carotene 725.7 μg; 1451.5 μg; and 2177.2 μg per day, respectively, for 6 weeks. The HC received high fat and fructose diet and the NC received a standard diet. The levels of triglyceride were analyzed using the colorimetric method before and after treatment. At the end of the study, the expression of SREBP-1c was identified by a quantitative polymerase chain reaction. RESULTS: High fat and fructose diet increased the levels of triglyceride (36.53 ± 1.27 vs. 119.79 ± 7.73), but high fiber and beta carotene diet can reduce triglyceride levels in HT1 (94.58 ± 4.53 vs. 77.70 ± 7.97); HT2 (115.58 ± 4.76 vs. 66.90 ± 3.11); and HT3 (103.87 ± 7.47 vs. 62.06 ± 4.45). The decreased triglyceride levels were related to low SREBP-1c gene expression, especially in the liver. Low SREBP-1c gene expression was correlated with homeostatic model assessment of insulin resistance index with r = 0.414; p < 0.05 in the liver and r = 0.158; p > 0.05 in white adipose tissues. CONCLUSION: High fiber and beta carotene diet can improve insulin resistance through inhibition of SREBP-1c gene expression.

This study aimed to investigate the effects of vitamin K2 supplementation in the form of menaquinone-7 (MK-7) on glucose, insulin, and lipid metabolism in patients with type 2 diabetes mellitus (T2DM). In this double-blinded, placebo-controlled, randomized trial, 68 insulin-independent people with diabetes received either 180 µg MK-7 twice a day or placebo for 12 weeks. We assessed fasting plasma glucose (FPG) and insulin concentrations (primary outcomes), glycated hemoglobin (HbA1c), insulin sensitivity indices, and lipid profiles (secondary outcomes) at baseline and end of the trial. At the end of the trial, FPG (effect size (ES) = − 0.68; p-adjusted = 0.031) and HbA1c (ES = − 0.36; p-adjusted = 0.004) were significantly lower in the vitamin K2 group compared with the placebo at the end of the trial. The number of participants achieved the target levels of glycemic control based on FPG, and HbA1c concentrations were significantly higher in the vitamin K2 group compared to the placebo group. Insulin concentrations (ES = − 0.29; p = 0.019) and homeostatic model assessment for insulin resistance (HOMA-IR) significantly decreased in the vitamin K2 group (ES = − 0.29; p = 0.019) compared to baseline, but their values were not significantly different compared to the placebo group at the end of the trial. No significant variation was observed in lipid profiles. Daily intake of 360 µg Vitamin K2 in the form of MK-7 for 12-weeks reduces FPG and HbA1c in patients with T2DM but does not have a lipid-lowering effect.

OBJECTIVE The purpose of this study was to evaluate the effects of zinc (Zn) supplementation on metabolic and neuroinflammatory parameters in cafeteria diet (CAF)-induced obesity in Wistar rats. METHODS Animals were divided into four groups: control diet (CT); CT+Zn; CAF; CAF+Zn. The diet was administered for 20 weeks; Zn treatment (10 mg/kg/d) started at week 16 and it was conducted until the end of the diet protocol. Weight gain, visceral fat, and plasma levels of glucose, triglycerides, insulin, TNF-α, and IL-6, as well as homeostatic model assessment of insulin resistance, were assessed. Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba-1) expression in the cerebral cortex and toll-like receptor 4 (TLR-4) in the cerebral cortex and hippocampus were evaluated. Memory was assessed by the novel object recognition test. RESULTS CAF diet increased weight gain, visceral fat, and plasma glucose, triglyceride, and TNF-α levels. Zn reversed the hyperglycemia caused by CAF diet and reduced IL-6 levels. In the cerebral cortex, GFAP was similar between groups; Iba-1 was increased by CAF diet but reduced in the CAF+Zn group. Zn reduced CAF-dependent TLR-4 increase in the hippocampus but not in the cerebral cortex. CAF-fed animals showed impaired recognition memory, whereas Zn reversed it. CONCLUSIONS These findings demonstrate that Zn partially reverted obesity-related metabolic dysfunction and reduced neuroinflammation and memory deficit caused by CAF diet.

Insulin-like growth factor-1 (IGF-1) is an anabolic hormone with myotrophic effects on muscle tissue. Patients with spinal muscular atrophy (SMA) sustain early-onset sarcopenia, which contributes to an increased prevalence of insulin resistance. Our aim was to determine the IGF-1 status in 5q-SMA patients and its association with insulin resistance. Real-life clinical and laboratory data of 34 patients (15 males; age 3 months-24 years) included: anthropometric measurements [weight, height/length, body mass index or weight-to-length ratio, delta-height standard deviation score (∆Ht SDS) as the difference between height/length SDS and mid-parental height (MPHt) SDS] and laboratory measurements [Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and IGF-1]. HOMA-IR levels categorized patients as insulin-resistant [HOMA-IR ≥1.9 (n = 20)] or insulin-sensitive [HOMA-IR

Background Pediatric obesity continues to remain a serious health concern which has significantly increased the morbidity risk in adulthood. Recent studies have analyzed the impact of the two adipokines, RBP4 (retinol binding protein 4) and STRA6 (stimulated by retinoic acid 6) in pediatric obese subjects with contradictory results. Methods An observational study was conducted in the Pediatric and Endocrinology Departments, Targu-Mures, Romania, including 213 children between 5-17 years of age, divided into two groups according to body mass index (BMI) standard deviation score (SDS): case (overweight or obese) and control (normal SDS). Age, sex, basic anthropometric and biochemical measurements and genotype of rs3758539, and rs10882280 for RBP4 gene and rs974456 and rs351224 of STRA6 gene were analyzed. Statistical analysis used SPSS v. 25.0, with a level of significance α = 0.05. Results There is no association between the two gene's polymorphisms and obesity in our pediatric population. In regression analysis, with HOMA IR (homeostatic model assessment of insulin resistance) as the outcome, the plasmatic level of RBP4 and fat mass percentage are significant predictors, with the model explaining 42% of the HOMA variability. Hypercholesterolemia was significantly associated with male sex, carrying variant allele and heterozygote status of rs10882280 RBP4 gene and wild-type allele rs351224 of STRA6 gene. Conclusion There is no significant association between obesity and SNPs of the RBP4 and STRA6 in our population, but they seem to play a role in insulin resistance and hypercholesterolemia.

Introduction Insulin resistance plays a major role in metabolic syndrome and is recognized as the most common risk factor for non-alcoholic fatty liver disease (NAFLD). Identifying predictors for insulin resistance could optimize screening and prevention. Purpose To evaluate the contribution of multiple single nucleotide polymorphisms across genes related to NAFLD and choline metabolism, in predicting insulin resistance in children with obesity. Methods One hundred fifty-three children with obesity (73 girls), aged 7-18 years, were evaluated within the NutriGen Study (ClinicalTrials.gov-NCT02837367). Insulin resistance was defined by Homeostatic Model Assessment for insulin-resistance cut-offs that accommodated pubertal and gender differences. Anthropometric, metabolic, intake-related variables, and 55 single nucleotide polymorphisms related to NAFLD and choline metabolism were evaluated. Gene-gene interaction effects were assessed using Multiple Data Reduction Software. Results Sixty percent (93/153) of participants showed insulin resistance (58.7% of boys, 63% of girls). Children with insulin resistance presented significantly higher values for standardized body mass index, triglycerides, transaminases and plasma choline when compared to those without insulin resistance. Out of 52 single nucleotide polymorphisms analysed, the interaction between genotypes CHDH(rs12676) and PNPLA3(rs738409) predicted insulin resistance. The model presented a 6/10 cross-validation consistency and 0.58 testing accuracy. Plasma choline levels and alanine aminotransferase modulated the gene interaction effect, significantly improving the model. Conclusion The interaction between genotypes in CHDH and PNPLA3 genes, modulated by choline and alanine aminotransferase levels, predicted insulin-resistance status in children with obesity. If replicated in larger cohorts, these findings could help identify metabolic risk in children with obesity.

Aim ANGPTL8 is a cytokine expressed and secreted by liver and adipose tissue, and is involved in glucose, lipid, and energy metabolism. Although studies have shown that ANGPTL8 is elevated in type 2 diabetes mellitus (T2DM) and cardiovascular disease, few have examined the association between ANGPTL8 single-nucleotide polymorphisms and the risk of macrovascular complications in T2DM patients. This study aimed to explore the relationship between rs2278426 and carotid intima-media thickening (cIMT) in T2DM. Methods A total of 217 T2DM patients and 201 healthy control subjects with normal glucose tolerance were recruited in the study. T2DM patients were divided into two groups: T2DM patients without cIM thickening (cIMT

Visceral adipose tissue dysfunction contributes to metabolic syndrome (MetS) and cardiovascular diseases. This study aims to investigate the association between visceral fat level measured by bioelectric impedance analysis (BIA) and MetS.This cross-sectional study recruited Taiwanese volunteers aged ≥20 years between 2012 and 2014. Anthropometric measurements and plasma concentrations of glucose, insulin, and lipid profiles were collected after at least 8 h of fasting. Insulin resistance was calculated by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Visceral fat level (VFL, ranges: 1-59) and trunk fat percentage were measured through by the Body Composition Analyzer TANITA AB 140 Viscan.A total of 1086 volunteers (mean age = 44.2 ± 13.2 years) were enrolled. Multiple regression analyses showed that triglycerides levels and blood pressure increased while high-density lipoprotein-cholesterol decreased with VFL in both genders (p0.05). Increased HOMA-IR and VFL had a synergistic effect on MetS. Higher VFL was independently associated with MetS in both men (OR = 1.33, 95% CI: 1.19-1.48) and women (OR = 1.28, 95% CI: 1.17-1.39).Higher VFL is associated with MetS and its components. The portable BIA machine is easily applicable and useful tool to measure visceral fat in the community setting.

Context Novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide demonstrated substantially greater glucose control and weight loss (WL) compared with selective GLP-1RA dulaglutide. Objective Explore mechanisms of glucose control by tirzepatide. Design Post hoc analyses of fasting biomarkers and multiple linear regression analysis. Setting Forty-seven sites in 4 countries. Patients or other Participants Three hundred and sixteen subjects with type 2 diabetes. Interventions Tirzepatide (1, 5, 10, 15 mg), dulaglutide (1.5 mg), placebo. Main Outcome Measures Analyze biomarkers of beta-cell function and insulin resistance (IR) and evaluate WL contributions to IR improvements at 26 weeks. Results Homeostatic model assessment (HOMA) 2-B significantly increased with dulaglutide and tirzepatide 5, 10, and 15 mg compared with placebo (P ≤ .02). Proinsulin/insulin and proinsulin/C-peptide ratios significantly decreased with tirzepatide 10 and 15 mg compared with placebo and dulaglutide (P ≤ .007). Tirzepatide 10 and 15 mg significantly decreased fasting insulin (P ≤ .033) and tirzepatide 10 mg significantly decreased HOMA2-IR (P = .004) compared with placebo and dulaglutide. Markers of improved insulin sensitivity (IS) adiponectin, IGFBP-1, and IGFBP-2 significantly increased by 1 or more doses of tirzepatide (P < .05). To determine whether improvements in IR were directly attributable to WL, multiple linear regression analysis with potential confounding variables age, sex, metformin, triglycerides, and glycated hemoglobin A1c was conducted. WL significantly (P ≤ .028) explained only 13% and 21% of improvement in HOMA2-IR with tirzepatide 10 and 15 mg, respectively. Conclusions Tirzepatide improved markers of IS and beta-cell function to a greater extent than dulaglutide. IS effects of tirzepatide were only partly attributable to WL, suggesting dual receptor agonism confers distinct mechanisms of glycemic control.

Iron overload has been recently shown to be associated with a hyperadrenergic state in genetic hemochromatosis. Whether this is also the case in essential hypertension, characterized by sympathetic activation and frequently by body iron overload, is unknown. In 17 healthy normotensive controls (age 52.3±3.2 years, mean±SE), in 21 age-matched patients with hypertension with iron overload (HT+), defined by serum ferritin levels, and in 28 hypertensives without this condition, we measured efferent postganglionic muscle sympathetic nerve traffic (microneurography), heart rate and blood pressure variability (power spectral analysis), serum ferritin, and metabolic variables. Muscle sympathetic nerve traffic was significantly ( P r =0.51, P r =0.47, P r =0.76, P r =0.46, P

MicroRNAs (miRs) are small non-coding RNAs that regulate the target gene expression. A change in miR profile in the pancreatic islets during diabetes is known, and multiple studies have demonstrated that miRs influence the pancreatic β-cell function. The miR-204 is highly expressed in the β-cells and reported to regulate insulin synthesis. Here we investigated whether the absence of miR-204 rescues the impaired glycemic control and obesity in the genetically diabetic (db/db) mice. We found that the db/db mice overexpressed miR-204 in the islets. The db/db mice lacking miR-204 (db/db-204−/−) initially develops hyperglycemia and obesity like the control (db/db) mice but later displayed a gradual improvement in glycemic control despite remaining obese. The db/db-204−/− mice had a lower fasting blood glucose and higher serum insulin level compared to the db/db mice. A homeostatic model assessment (HOMA) suggests the improvement of β-cell function contributes to the improvement in glycemic control in db/db-204−/− mice. Next, we examined the cellular proliferation and endoplasmic reticulum (ER) stress and found an increased frequency of proliferating cells (PCNA + ve) and a decreased CHOP expression in the islets of db/db-204−/− mice. Next, we determined the effect of systemic miR-204 inhibition in improving glycemic control in the high-fat diet (HFD)-fed insulin-resistant mice. MiR-204 inhibition for 6 weeks improved the HFD-triggered impairment in glucose disposal. In conclusion, the absence of miR-204 improves β-cell proliferation, decreases islet ER stress, and improves glycemic control with limited change in body weight in obese mice.

Metabolic syndrome (MetS) is an increasing health threat and often leads to cardiovascular complications. The aim of this study was to evaluate icariin’s ability to combat MetS induced in rats and outline the involved mechanisms for action. Rats were grouped in four batches. The controls received a regular diet and water. MetS was induced in the remaining three groups using a high-salt high-fructose diet. Groups 1 and 2 were given daily doses of saline, while Groups 3 and 4 received 25 and 50 mg/kg icariin, respectively, for 12 weeks in total. The experimental protocol was carried out for 12 weeks consecutively. Icariin significantly decreased body mass index (BMI), adiposity index and body weight. Further, icariin protected against dyslipidemia, hyperglycemia, and hyperinsulinemia and improved insulin resistance as given by the homeostatic model assessment of insulin resistance (HOMA-IR) values. Icariin guarded against the rise in serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). In addition, it significantly inhibited the decrease in mRNA expression of glucose transporter type 4 (GLUT4) and liver kinase B1 (LKB1). These effects were accompanied by decreased liver content of nuclear factor kappa B (NFκB) and enhanced serum levels of phosphorylated 5ʹ-adenosine monophosphate-activated protein kinase (p-AMPK). Further, icariin significantly increased p-AMPK/AMPK ratio in liver tissues. Conclusively, icariin offers protection in experimentally induced MetS, partially due to AMPK activation.

Background: Hidradenitis suppurativa is a chronic inflammatory skin disease of terminal follicular acroinfundibulum. Objectives: This study aimed to evaluate serum irisin, plasma glucose, insulin, and lipid levels in hidradenitis suppurativa, and elucidate possible associations with disease activity, inflammatory, or metabolic parameters. Methods: This case-control study included 37 patients (M/F: 9/28) and 37 sex-, age- and body mass index -matched healthy controls (M/F: 11/26). Demographic data, Hurley stage of disease, fasting glucose, insulin, total cholesterol, high density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, C-reactive protein levels, erythrocyte sedimentation rate, hematologic parameters, and serum irisin were assessed. Results: The hidradenitis suppurativa group had significantly higher waist circumference than controls (p < 0.001). Insulin resistance, defined as a homeostatic model assessment for insulin resistance value greater than 2.5, was observed in 45.9% of patients and 8.1% of controls (p = 0.003), whereas metabolic syndrome was observed in 32.4% of patients and 5.4% of controls (p < 0.001). Furthermore, plasma triglycerids, glucose, and insulin levels were significantly higher in the hidradenitis suppurativa (p = 0.013, p = 0.001, and p = 0.004), respectively. Mean irisin level was insignificantly higher in the hidradenitis suppurativa group (37.4 ± 32.6) than in controls (26.2 ± 24.7, p = 0.217). Study limitation: Physical activity and the exercise levels of participants were not documented. Conclusion: This study indicates that hidradenitis suppurativa patients have higher serum irisin, fasting plasma glucose, insulin, and triglycerides levels than healthy controls. Thus, the authors suggest that hidradenitis suppurativa patients should be evaluated for insulin resistance and metabolic syndrome, and monitored accordingly.

BackgroundRecent study showed that individuals with type 2 diabetes have a high risk of developing colorectal cancer (CRC), in which Receptor for Advanced Glycation End Products (RAGE) plays a pivotal role. We conducted a cross-sectional study to examine the relationships of circulating sRAGE, CRC and other clinical factors in type2 diabetes patients.MethodsA total of 150 type 2 diabetes patients aged 50 years and older were enrolled, including 50 patients with CRC and 100 patients without CRC. We measured Serum levels of sRAGE and interleukin-6(IL-6) using an enzyme-linked immunosorbent assay (ELISA). In addition, other clinical parameters were also measured during hospitalization.ResultsType 2 diabetes patients with CRC had higher triglyceride, total cholesterol, IL-6, and circulating sRAGE levels and lower use of medicines than type 2 diabetes patients without CRC. Circulating sRAGE was associated with an increased risk for CRC (OR = 2.289 for each SD increase in sRAGE, 95% CI = 1.037–5.051;P = 0.04) among Type 2 diabetes patients after adjustment for confounders. Furthermore, circulating sRAGE levels among type 2 diabetes patients were positively correlated with triglyceride (r = 0.377,P r = 0.491,P r = 0.330,P r = 0.194,P = 0.017); and fasting serum insulin (r = 0.167,P = 0.041) and IL-6 (r = 0.311,P ConclusionsOur results suggested that circulating sRAGE is independently risk factor for CRC, and also closely related to inflammation, dyslipidemia in type 2 diabetes patients.

Background: Data on the effects of excess aldosterone on glucose metabolism are inconsistent. This study compared the changes in glucose metabolism in patients with primary aldosteronism (PA) after adrenalectomy or treatment with a mineralocorticoid receptor antagonist (MRA).Methods: Overall, 241 patients were enrolled; 153 underwent adrenalectomy and 88 received an MRA. Fasting glucose, homeostatic model assessment of insulin resistance (HOMA-IR), and homeostatic model assessment of β-cell function (HOMA-β) were compared between the treatment groups after 1 year. Plasma aldosterone concentration (PAC) and factors determining HOMA-IR and PAC were evaluated.Results: No baseline differences were observed between the groups. Fasting insulin, HOMA-IR, and HOMA-β increased in both groups and there were no significant differences in fasting glucose following treatment. Multiple regression analysis showed associations between PAC and HOMA-IR (β=0.172, P=0.017) after treatment. Treatment with spironolactone was the only risk factor associated with PAC >30 ng/dL (odds ratio, 5.2; 95% confidence interval [CI], 2.7 to 10; PP=0.007).Conclusion: Spironolactone treatment might increase insulin resistance in patients with PA. This strengthened the current recommendation that adrenalectomy is the preferred strategy for patient with positive lateralization test. Achieving a post-treatment PAC of

Diabetic nephropathy (DN) is a master cause of all surplus death-rate among type 2 diabetes mellitus (T2DM) patients with microalbuminuria. This study aimed to find effective biomarkers for early predicting of DN. Present study included 63 patients with T2DM (31 patients with DN, 32 patients without DN) and 33 healthy controls. These three groups were matched for their glucose, urea, creatinine, insulin, L-Carnitine (LC), osteoprotegerin (OPG), sialic acid (SA), trace elements (Selenium, Zinc, Magnesium), albumin (Alb), and fibronectin (FN). Glucose, urea, and creatinine were determined by spectrophotometer. Insulin, LC, OPG, SA, Alb, and FN were assayed by enzyme-linked immunosorbent assay (ELISA). Insulin resistance (IR) was calculated by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) equation. Selenium was measured by hydride generation while Zinc and Magnesium were measured by flame atomic absorption spectrometer. Compared with controls, the results indicated that T2DM patients with or without DN had a significant increase in glucose, urea, creatinine, insulin, IR, OPG, SA, Alb, FN and a significant decrease in LC and trace elements levels. It was concluded that IR is strongly associated with obesity and had an important role in the pathogenesis and increased complication of diabetes which could be used as excellent indicators for early-stage DN in T2DM patients and thus decreasing mortality and morbidity. Key words: Diabetic nephropathy, insulin resistance, obesity, oxidative stress, traces elements.

Background: Previous studies have demonstrated that aerobic exercise (AE) and the Dietary Approaches to Stop Hypertension (DASH) diet can improve neurocognition. However, the mechanisms by which lifestyle improves neurocognition have not been widely studied. We examined the associations between changes in metabolic, neurotrophic, and inflammatory biomarkers with executive functioning among participants from the Exercise and Nutritional Interventions for Neurocognitive Health Enhancement (ENLIGHTEN) trial. Objective: To examine the association between changes in metabolic function and neurocognition among older adults with cognitive impairment, but without dementia (CIND) participating in a comprehensive lifestyle intervention. Methods: ENLIGHTEN participants were randomized using a 2×2 factorial design to receive AE, DASH, both AE+DASH, or a health education control condition (HE) for six months. Metabolic biomarkers included insulin resistance (homeostatic model assessment [HOMA-IR]), leptin, and insulin-like growth factor (IGF-1); neurotrophic biomarkers included brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF); and inflammatory biomarkers included interleukin-6 (IL-6) and C-Reactive Protein (CRP). Results: Participants included 132 sedentary older adults (mean age = 65 [SD = 7]) with CIND. Results demonstrated that both AE (d = 0.48, p = 0.015) and DASH improved metabolic function (d = 0.37, p = 0.039), without comparable improvements in neurotrophic or inflammatory biomarkers. Greater improvements in metabolic function, including reduced HOMA-IR (B = –2.3 [–4.3, –0.2], p = 0.033) and increased IGF-1 (B = 3.4 [1.2, 5.7], p = 0.004), associated with increases in Executive Function. Conclusion: Changes in neurocognition after lifestyle modification are associated with improved metabolic function.

Summary Objective Abdominal fat ultrasound (US) is a simple clinical tool that may allow measures of fat depots not visible using common dual‐energy X‐ray absorptiometry (DEXA) or computerized tomography (CT) imaging. The aim of this study was to validate the technique, give measures of superficial and profound subcutaneous, preperitoneal, omental and perirenal (retroperitoneal) fat and correlate them with MS markers. Methods Sequential US measures of these five abdominal fat layers were done at 397 adults. Blood pressure (BP), body mass index (BMI), waist, body fat %, HOMA‐IR index (homeostatic model assessment of insulin resistance), lipid profile and leptin were recorded. Metabolic syndrome (MS) was defined according to Cholesterol education programme adult treatment panel III (ATPIII) criteria. Results Subcutaneous and omental fat were increased among people with obesity, whereas preperitoneal and perirenal fat did not show any difference according to BMI or waist. Women showed thicker subcutaneous fat (both superficial and profound), whereas men had bigger omental fat. Both postmenopausal and diabetic patients had changes in omental fat only, whereas patients with fatty liver showed thicker preperitoneal and perirenal fat, as well. MS patients showed both thicker perirenal and omental fat. A cut‐off of 54 mm in male (M)/34 mm in female (F) of omental fat and 22.5 mm (M)/12.5 mm (F) of perirenal fat could be predictive of later MS onset. Conclusions US is a valid method to measure all different abdominal fat depots. Omental and perirenal fat measures may classify patients at risk for MS. Preperitoneal fat depot may also correlate with fatty liver disease.

Background Lipoprotein insulin resistance (LPIR) score is a composite biomarker representative of atherogenic dyslipidemia characteristic of early insulin resistance. It is elevated in obesity and may provide information not captured in glycosylated hemoglobin and homeostatic model assessment for insulin resistance. While bariatric surgery reduces diabetes incidence and resolves metabolic syndrome, the effect of bariatric surgery on LPIR is untested. Objectives We sought to assess the effects of Roux-en-Y gastric bypass and sleeve gastrectomy on LPIR in nondiabetic women with obesity. Setting Nonsmoking, nondiabetic, premenopausal Hispanic women, age ≥18 years, undergoing Roux-en-Y gastric bypass or sleeve gastrectomy at Bellevue Hospital were recruited for a prospective observational study. Methods Anthropometric measures and blood sampling were performed preoperatively and at 6 and 12 months postoperatively. LPIR was measured by nuclear magnetic resonance spectroscopy. Results Among 53 women (Roux-en-Y gastric bypass, n = 22; sleeve gastrectomy, n = 31), mean age was 32 ± 7 years and body mass index 44.1 ± 6.4 kg/m2. LPIR was reduced by 35 ± 4% and 46 ± 4% at 6 and 12 months after surgery, respectively, with no difference by procedure. Twenty-seven of 53 patients met International Diabetes Federation criteria for metabolic syndrome preoperatively and had concomitant higher homeostatic model assessment for insulin resistance, glycosylated hemoglobin, nonhigh-density lipoprotein-cholesterol and LPIR. Twenty-five of 27 patients experienced resolution of metabolic syndrome postoperatively. Concordantly, the preoperative differences in homeostatic model assessment for insulin resistance, glycosylated hemoglobin, and nonhigh-density lipoprotein-cholesterol between those with and without metabolic syndrome resolved at 6 and 12 months. In contrast, patients with metabolic syndrome preoperatively exhibited greater LPIR scores at 6 and 12 months postoperatively. Conclusion This is the first study to demonstrate improvement in insulin resistance, as measured by LPIR, after bariatric surgery with no difference by procedure. This measure, but not traditional markers, was persistently higher in patients with a preoperative metabolic syndrome diagnosis, despite resolution of the condition.

Many studies suggest that Epigallocatechin-3-Gallate (EGCG) has many protective effects. But little is known about its protective effects against chronic restraint stress-induced damage in rats. The aim was to demonstrate the potential protective effects of EGCG against harmful pancreatic damage to the immobilization stress in the rat model. Forty rats, 2 months old, were divided into four groups (n = 10): control group; EGCG group, rats received EGCG by gavage (100 mg/kg /day) for 30 days; stressed group, rats exposed to immobilization stress; and stressed with EGCG group, rats exposed to immobilization stress and received EGCG for 30 days. Glycemic status parameters, corticosterone, and inflammatory markers were investigated on the first day, 15th day, and the 30th day of the experiment. Pancreatic oxidative stress markers and cytokines were evaluated. Histological, immunohistological, and statistical studies were performed. On the 15th day, fasting blood glucose (FBG), fasting plasma insulin (FPI), homeostatic model assessment for insulin resistance (HOMA-IR), and fasting plasma corticosterone were significantly higher in the stressed group when compared with first and 30th day in the same group as well as when compared with control and stressed with EGCG groups. The stressed group revealed significantly higher pancreatic IL-1β, IL-6, TNF-α, MDA, and NO, serum amylase and serum lipase, and significantly lower GSH, SOD, and CAT when compared to control and stressed with EGCG groups. EGCG treatment attenuated the pancreatic stress-induced cellular degeneration, leucocytic infiltration, and cytoplasmic vacuolations; significantly decreased area percentage of collagen fibers; and significantly increased mean area percentage of insulin immunopositive cell as compared with stressed group. EGCG is a protective agent against immobilization stress because of its anti-diabetic, anti-inflammatory, and and anti-oxidative stress properties, as confirmed by biochemical and histological alterations.

BACKGROUND: The normal-weight BMI range (18.5–24.9 kg/m(2)) includes adults with body shape and cardiometabolic disease risk features of excess adiposity, although a distinct phenotype developed on a large and diverse sample is lacking. OBJECTIVE: To identify demographic, behavioral, body composition, and health-risk biomarker characteristics of people in the normal-weight BMI range who are at increased risk of developing cardiovascular and metabolic diseases based on body shape. METHODS: Six nationally representative waist circumference index (WCI, weight/height(0.5)) prediction formulas, with BMI and age as covariates, were developed using data from 17,359 non-Hispanic (NH) white, NH black, and Mexican-American NHANES 1999–2006 participants. These equations were then used to predict WCI in 5594 NHANES participants whose BMI was within the normal weight range. Men and women in each race/Hispanic-origin group were then separated into high, medium, and low tertiles based on the difference (residual) between measured and predicted WCI. Characteristics were compared across tertiles; P values for significance were adjusted for multiple comparisons. RESULTS: Men and women in the high WCI residual tertile, relative to their BMI and age-equivalent counterparts in the low tertile, had significantly lower activity levels; higher percent trunk and total body fat (e.g. NH white men, X ± SE, 25.3 ± 0.2% compared with 20.4 ± 0.2%); lower percent appendicular lean mass (skeletal muscle) and bone mineral content; and higher plasma insulin and triglycerides, higher homeostatic model assessment of insulin resistance (e.g. NH white men, 1.45 ± 0.07 compared with 1.08 ± 0.06), and lower plasma HDL cholesterol. Percent leg fat was also significantly higher in men but lower in women. Similar patterns of variable statistical significance were present within sex and race/ethnic groups. CONCLUSIONS: Cardiometabolic disease risk related to body shape in people who are normal weight according to BMI is characterized by a distinct phenotype that includes potentially modifiable behavioral health risk factors.

Background Diabetes is a progressive disease that increases glucose levels in the blood. While studies have shown that patients with pulmonary disease (both obstructive and restrictive pulmonary disease) have a higher prevalence of type 2 diabetes mellitus (T2DM), there have been more studies on restrictive patterns than chronic obstructive pulmonary disease. Aim To assess whether restrictive and obstructive pulmonary diseases are associated with T2DM in Koreans. Methods For our analysis, we used data from the Korea National Health and Nutrition Examination Survey. A total of 2830 subjects were included in this study. Spirometry results were categorized into three patterns: Normal, restrictive pulmonary disease (RPD), and obstructive pulmonary disease (OPD). Results The factors used as diabetic indicators (i.e. homeostatic model assessment of insulin resistance, homeostatic model assessment of beta-cell function, glycated hemoglobin, and fasting insulin) were among the highest in RPD but not in OPD. Based on multivariate logistic regression analysis, subjects with RPD were found with an increased odds ratio [OR: 1.907, 95% confidence interval (CI): 1.110-3.277] for T2DM compared with subjects with normal pulmonary function, whereas in patients with OPD, the OR had not increased. Model 4, which adjusted for the variables that could affect diabetes and pulmonary disease, showed a significant increase in the T2DM OR to RPD (OR: 2.025, 95%CI: 1.264-3.244). On the other hand, no statistically significant difference was shown in OPD (OR: 0.982, 95%CI: 0.634-1.519). Conclusion RPD, not OPD, is highly associated with T2DM regardless of the risk factors of various T2DMs that can be confounds.

Background: Childhood rheumatologic disorders are multisystem diseases characterized by inflammation, damage, and/or pain of the joints, and connective tissues. Aim: This study aimed to detect the presence of insulin resistance (IR) in pediatric patients with systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) which can lead to the development of diabetes mellitus. Subjects and Methods: This case-control study was performed on 60 SLE, 60 RA patients, and 60 healthy subjects as a control group. All subjects were subjected to detailed history taking, physical examination, and laboratory investigations including determination of fasting blood glucose (FBG), total cholesterol, triglyceride (TG), HDL, LDL, and fasting insulin. Homeostatic model assessment of insulin resistance (HOMA IR) was calculated. Results: There was no significant difference in the age, and FBG in the three studied groups but there was a significant difference as regard platelets counts, hemoglobin, ESR, CRP, TG, HDL, fasting insulin levels, and HOMA IR. There is no significant difference between the SLE, and RA in disease duration, ESR, CRP, HDL, LDL, triglyceride, cholesterol, fasting blood glucose, fasting insulin levels, and HOMA IR. There were significant positive correlations between HOMA IR with patients’ BMI, ESR, CRP, TG, FBG, and fasting insulin levels in both SLE and RA groups. Conclusions: SLE, and RA patients had a higher insulin resistance than age-matched healthy controls which can lead to the development of type 2 diabetes mellitus. HOMA IR had positive correlations with BMI, TG, FBG, and fasting insulin levels in both SLE and RA groups.

Background : Sodium-glucose cotransporter 2 inhibitors reduce the risk of cardiovascular death in individuals with type 2 diabetes mellitus (T2DM) and cardiovascular disease, but the effect of these inhibitors on early cardiovascular disease remains unknown. This study evaluated the effect of dapagliflozin on the metabolic profiles and endothelial cell function in obese patients with T2DM without established cardiovascular disease. Methods : We enrolled 140 patients with a mean age, weight, and body mass index (BMI) of 47 years, 83 kg, and 30.3 kg/m², respectively. Dapagliflozin (10 mg daily for 6 months) was administered to obese patients with T2DM without established cardiovascular disease. Participants’ weight, BMI, body fat mass (BFM), muscle mass, glycosylated hemoglobin (HbA1c), lipid profile, waist to hip ratio (WHR), and pulse wave velocity (PWV) were measured at baseline and after 6 months. Results : Participants experienced statistically significant reductions in their HbA1c, fasting plasma glucose, low-density lipoprotein cholesterol, total cholesterol, body weight, BMI, WHR, BFM, and aortic PWV, without a significant change in their muscle mass, extracellular fluid, or intracellular volume. Statistically significant reductions in aortic PWV were associated with a decrease in BFM, visceral fat, WHR, and homeostatic model assessment of insulin resistance. Conclusion : Dapagliflozin may be beneficial in preventing early cardiovascular disease in obese patients with T2DM without established cardiovascular disease.

Aim: Insulin resistance is the precursor pathway leading to type 2 diabetes and is present long before diabetes is diagnosed. The triglyceride-glucose index (TyG index) is a simple, reliable, cost-effective screening method that has recently been used for screening insulin resistance. The aim of our study is to evaluate whether TyG index can be used as insulin resistance marker in patients with thyroid disease. Materials and Methods: The registry files of 1280 patients applied to the obesity outpatient clinic between 15.04.2016-15.10.2017 were screened for this retrospective study. 604 patients of whom glucose, triglyceride and TSH levels were recorded in their files and TSH levels were 0.5-10 mU/ml were included in the study. Approval was obtained from Noninvasive Ethics Committee before starting the study. The presence of insulin resistance was determined according to the level of the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). It was assumed that patients with HOMA-IR≥2.5 had insulin resistance. A Pearson and Spearman correlation analyze was used for the evaluation of the relationship between variables. ROC analysis was used to determine the predictability of TyG index to diagnose insulin resistance and cut-off points. P

Background. Testosterone replacement therapy (TRT) is commonly used for the treatment of hypogonadism in men, which is often associated with type 2 diabetes mellitus (T2DM) and metabolic syndrome (Mets). Recent compiling evidence shows that TRT has beneficial metabolic effects on these patients. Objective. A meta-analysis has been conducted to evaluate the effects of TRT on cardiovascular metabolic factors. Methods. We conducted a systemic search on PubMed, Embase, Cochrane Library, Wanfang, and CNKI and selected randomized controlled trials (RCTs) to include. The efficacy of TRT on glycemia, insulin sensitivity, lipid profile, and body weight was meta-analyzed by Review Manager. Results. A total of 18 RCTs, containing 1415 patients (767 in TRT and 648 in control), were enrolled for the meta-analysis. The results showed that TRT could reduce HbA1c (MD = −0.67, 95% CI −1.35, −0.19, and P = 0.006 ) and improve HOMA-IR (homeostatic model assessment of insulin resistance) (SMD = −1.94, 95% CI −2.65, −1.23, and P < 0.0001 ). TRT could also decrease low-density lipoprotein (SMD = −0.50, 95% CI −0.82, −0.90, and P = 0.002 ) and triglycerides (MD = −0.64, 95% CI −0.91, −0.36, and P < 0.0001 ). In addition, TRT could reduce body weight by 3.91 kg (MD = −3.91, 95% CI −4.14, −3.69, and P < 0.00001 ) and waist circumference by 2.8 cm (MD −2.80, 95% CI −4.38, −1.21 and P = 0.0005 ). Erectile dysfunction (measured by IIEF-5) did not improve, while aging-related symptoms (measured by AMS scores) significantly improved. Conclusions. TRT improves glycemic control, insulin sensitivity, and lipid parameters in hypogonadism patients with T2DM and MetS, partially through reducing central obesity.

Introduction The objective of this study was to examine changes in hemoglobin A1c (HbA1c), anti-diabetic medication use, insulin resistance, and other ambulatory glucose profile metrics between baseline and after 90 days of participation in the Twin Precision Nutrition (TPN) Program enabled by Digital Twin Technology. Methods This was a retrospective study of patients with type 2 diabetes who participated in the TPN Program and had at least 3 months of follow-up. The TPN machine learning algorithm used daily continuous glucose monitor (CGM) and food intake data to provide guidelines that would enable individual patients to avoid foods that cause blood glucose spikes and to replace them with foods that do not produce spikes. Physicians with access to daily CGM data titrated medications and monitored patient conditions. Results Of the 89 patients who initially enrolled in the TPN Program, 64 patients remained in the program and adhered to it for at least 90 days; all analyses were performed on these 64 patients. At the 90-day follow-up assessment, mean (± standard deviation) HbA1c had decreased from 8.8 ± 2.2% at baseline by 1.9 to 6.9 ± 1.1%, mean weight had decreased from 79.0 ± 16.2 kg at baseline to 74.2 ± 14.7 kg, and mean fasting blood glucose had fallen from 151.2 ± 45.0 mg/dl at baseline to 129.1 ± 36.7 mg/dl. Homeostatic model assessment of insulin resistance (HOMA-IR) had decreased by 56.9% from 7.4 ± 3.5 to 3.2 ± 2.8. At the 90-day follow-up assessment, all 12 patients who were on insulin had stopped taking this medication; 38 of the 56 patients taking metformin had stopped metformin; 26 of the 28 patients on dipeptidyl peptidase-4 (DPP-4) inhibitors discontinued DPP-4 inhibitors; all 13 patients on alpha-glucosidase inhibitors discontinued these inhibitors; all 34 patients on sulfonylureas were able to stop taking these medications; two patients stopped taking pioglitazone; all ten patients on sodium-glucose cotransporter-2 (SGLT2) inhibitors stopped taking SGLT2 inhibitors; and one patient stopped taking glucagon-like peptide-1 analogues. Conclusion The results provide evidence that daily precision nutrition guidance based on CGM, food intake data, and machine learning algorithms can benefit patients with type 2 diabetes. Adherence for 3 months to the TPN Program resulted in patients achieving a 1.9 percentage point decrease in HbA1c, a 6.1% drop in weight, a 56.9% reduction in HOMA-IR, a significant decline in glucose time below range, and, in most patients, the elimination of diabetes medication use.

Background High-intensity statin is recommended in high-risk type 2 diabetes (T2D); however, statin dose dependently increases the risk of developing new-onset diabetes, can potentially worsen glycemic control in T2D, and may cause cognitive impairment. This study aimed to investigate the effect of statin intensification on glucose homeostasis and cognitive function in T2D. Materials and methods T2D patients who were taking simvastatin ≤20 mg/day were randomized to continue taking the same dosage of simvastatin (low-dose simvastatin group; LS, n=63) for 12 weeks, or to change to atorvastatin 40 mg/day for 6 weeks, and if tolerated, atorvastatin was increased to 80 mg/day for 6 weeks (high-dose atorvastatin group; HS, n=62). Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and of β-cell function (HOMA-B), cognitive functions using Montreal Cognitive Assessment (MoCA), and Trail Making Test (TMT) were assessed at baseline, 6 weeks, and 12 weeks. Results Mean age of patients was 58.8±8.9 years, and 72% were female. Mean baseline FPG and HbA1c were 124.0±27.5 mg/dl and 6.9±0.8%, respectively. No differences in baseline characteristics between groups were observed. Change in HbA1c from baseline in the LS and HS groups was -0.1% and +0.1% (p=0.03) at 6 weeks, and -0.1% and +0.1% (p=0.07) at 12 weeks. There were no significant differences in FPG, fasting plasma insulin, HOMA-B, HOMA-IR, MoCA score, or TMT between groups at 6 or 12 weeks. Conclusion Switching from low-dose simvastatin to high-dose atorvastatin in T2D resulted in a slight increase in HbA1c (0.1%) without causing cognitive decline.

Conflicting results have been reported on the association of fat-free mass (FFM) and insulin resistance (IR). This study sought to test the association of FFM and IR by indexing FFM to avoid collinearity with fat mass. This cross-sectional study comprised 11,284 volunteers, aged 38–79 years. Body composition was assessed by multi-frequency bioelectrical impedance. FFM indexed to body surface area (FFMbsa) was calculated. IR and impaired glucose tolerance (IGT) were estimated with homeostatic model assessment of insulin resistance index (HOMA-IR) and 2-h oral glucose tolerance test (2h-OGTT), respectively. Percent body fat decreased from the 1st to the 5th quintile of FFMbsa in both women (Eta2 = 0.166) and men (Eta2 = 0.133). In women, fasting insulin (Eta2 = 0.002), glucose (Eta2 = 0.006), and HOMA-IR (Eta2 = 0.007) increased slightly, but 2-h plasma glucose (2-h PG) was similar across the quintiles of FFMbsa. In men, fasting insulin and HOMA-IR were similar across the quintiles of FFMbsa, whereas fasting glucose increased slightly (Eta2 = 0.002) and 2-h PG decreased (Eta2 = 0.005) toward the highest quintile of FFMbsa. The higher the odds ratio for IR, the greater the FFMbsa in both sexes. Differently, FFMbsa did not affect the odds of IGT in women, while in men the odds ratio for IGT was lower in the 5th quintile compared with the 1st quintile of FFMbsa. Higher odds of IR associated with greater FFMbsa contrasted with lower odds of IGT associated with greater FFMbsa. IR may be misdiagnosed by HOMA-IR in adults with greater fat-free mass.

Objectives To evaluate the effect of generic sofosbuvir and daclatasvir (SOF/DCV) treatment on the glycemic state and insulin resistance as well as lipid profiles of those who achieved sustained virological response (SVR) in diabetic chronic hepatitis C virus (CHC) patients. Methods We retrospectively reviewed 114 CHC patients with evidence of type 2 diabetes that were treated with generic SOF/DCV between May 2016 and August 2017. Baseline demographic and laboratory data were recorded. At 12-week post end of therapy (SVR12), glycemic state and insulin resistance as well as lipid profiles were re-evaluated and compared with baseline. Results A total of 98 diabetic CHC patients were finally included and were responders. A significant decline in the glycemic state as well as Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) values (P ≤ 0.0001) was observed, but HOMA-S showed a statistically significant increase (P ≤ 0.0001) at SVR12 in comparison to baseline values. Also, a significant increase in serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol levels was observed at SVR12 compared to baseline, but serum triglycerides levels showed a significant decrease. Logistic regression showed that the higher baseline HOMA-IR was a significant predictive variable of a decrease ≥20% of HOMA-IR, while higher baseline HOMA-IR and baseline triglycerides emerged as the only significant predictors of the Δ increase LDL-C level at SVR12. Conclusion SOF/DCV-based therapy led to an improvement of glycemic state associated with a global worsening of lipid profile. Further studies are strongly warranted to evaluate the cardiovascular balance between amelioration of insulin resistance and negative changes of the lipid profile.

Introduction. The prevalence of obesity is increasing worldwide in high, low, and middle-income countries such as Indonesia. Obesity rate is higher in females in Indonesia. Obesity has important contribution in the occurrence of insulin resistance (IR) and type 2 diabetes mellitus. Several anthropometric measurements such as waist circumference (WC), body mass index (BMI), body mass (BM), total body fat percentage (Fat%) and visceral fat (VF) are related to IR. This study aimed to investigate which of those measurements could be used as a better predictor of IR in non-menopausal Indonesian adult females. Methods. Total of 80 non-menopausal Indonesian adult females ranging from 21 to 40 years were recruited in this study. Insulin resistance was measured by using Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) equation. Subjects with HOMA-IR index >75th percentile with cut-off 2.74 were defined as IR. Waist circumference, BMI and BM were measured, while TF and VF were measured by bioelectrical impedance analysis (BIA). Results. HOMA-IR had significant correlation with WC (r = 0.563, p < 0.001), BMI (r = 0.537, p < 0.001), BM (r = 0.515, p < 0.001), VF (r = 0.515, p < 0.001), Fat% (r = 0.490, p < 0.001). The area under curve of VF (0.809), BMI (0.807), WC (0.805), and BM (0.799) are slightly larger than and Fat% (0.766). Conclusion. Insulin resistance had strong correlation with all anthropometric measurements, but the correlation was less significant with Fat%.

This cross-sectional study investigates the association between insulin resistance (IR) and serum uric acid (sUA) and relative fat (RFM) and lean mass (RLM) profiles in children with chronic kidney disease (CKD). RLM and RFM were assessed by bioimpedance spectroscopy in 41 children and adolescents. Normal weight obesity (NWO) was defined as normal height-age body mass index and RFM >85th percentile, according to age and sex. Homeostatic model assessment of insulin resistance (HOMA-IR) level >95th percentile, according to sex and pubertal stage, and sUA >7 mg/dl were used to define IR and hyperuricemia, respectively. High RFM (15 patients) and NWO (7 patients) were associated with higher HOMA-IR in total (p

Background Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD, a common cause of liver disease, with increased chance of progression to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Circulating leptin is increased in patients with NASH. It is an independent positive predictor of the severity of hepatic steatosis. Vitamin D is a lipophilic molecule essential to maintain calcium and phosphate balance. Moreover, it has antifibrotic, antiproliferative, and anti-inflammatory effects on the liver. Vitamin D deficiency is a worldwide condition and very common in patients with NASH. Low serum vitamin D has been shown to predispose to intrahepatic lipid accumulation leading to NAFLD. The aim of this study was to investigate the association of vitamin D supplementation with serum leptin and metabolic parameters in Egyptian patients with non-alcoholic steatohepatitis Results Patients with NASH group had statistically significant higher values of diastolic blood pressure (94.3 ± 11.9 mmHg, p < 0.0001), glycated hemoglobin (8.0 ± 2.4%, p < 0.0001), fasting blood sugar (165.6 ± 62.0 mg/dL, p < 0.0001), fasting insulin level (24.2 ± 3.0 μU/ml, p < 0.0001), homeostatic model assessment of insulin resistance (HOMA-IR) (1.8 ± 0.7, p < 0.0001), alanine transferase (ALT) (78.2 ± 36.7 U/L, p < 0.0001), aspartate transferase (AST) (108.6 ± 85.6 U/L, p < 0.0001), NAFLD fibrosis score (− 0.78 ± 0.9, p < 0.0001), total cholesterol (233.0 ± 40.9 mg/dL, p = 0.0011), low-density lipoprotein (117.5 ± 41.6 mg/dL, p = 0.0084), and triglycerides (229.7 ± 62.1 mg/dL, p < 0.0001) than the control group. Moreover, they had lower serum vitamin D level (15.6 ± 6.6 ng/ml, p = 0.0004) and higher serum leptin level (35.9 ± 28.4 ng/ml, p < 0.0001) than the control group. Following vitamin D supplementation, there was a statistically significant reduction in HbA1c (6.8 ± 1.3%, p = 0.0055), fasting blood sugar (136.1 ± 32.7 mg/dL, p = 0.0094), fasting insulin level (22.9 ± 1.8 μU/ml, p = 0.0236), HOMA-IR (1.4 ± 0.4, p = 0.0026), ALT (55.3 ± 21.3 U/L, p = 0.0010), AST (73.1 ± 54.2 U/L, p = 0.0297), and triglycerides (203.6 ± 49.8 mg/dL, p = 0.0415) in patients with NASH. There was a statistically significant increase in serum vitamin D level (33.0 ± 7.6 ng/ml, p < 0.0001) and decrease in serum leptin level (23.5 ± 12.9 ng/ml, p = 0.0140) after treatment. Conclusions Vitamin D supplementation in patients with NASH in a dose of 4000 IU/day for 12 weeks improves severity of hepatic inflammation, decreases insulin resistance, improves glycemic control, corrects dyslipidemia, and protects against lipotoxicity by inhibition of serum leptin.

Background. Serum bilirubin is an endogenous antioxidant that has protective effects against obesity-related metabolic diseases. Objectives. This study aimed to evaluate the characteristics of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) and their relationships with insulin sensitivity in obese patients with impaired glucose regulation and type 2 diabetes mellitus (IGR/T2DM) in China. Patients and Methods. Cohort 1 comprised obese patients (n = 71) was divided into the IGR/T2DM group (n = 38, obesity with IGR/T2DM) and control group (n = 33, obesity without IGR/T2DM). Insulin sensitivity was evaluated using the hyperinsulinemic-euglycemic clamp technique (HEC) with glucose disposal rate (GDR, M value). Cohort 2 comprised obese patients with IGR/T2DM who underwent metabolic surgery (n = 109) as complementary to cohort 1. Insulin sensitivity was evaluated with the Matsuda Index and homeostatic model assessment of insulin sensitivity (HOMA-IS). Results. In cohort 1, TBIL, DBIL, and IBIL were higher within the physiological range in the IGR/T2DM group compared with the control group; IBIL was positively correlated with M value (r = 0.342, p=0.044) in the IGR/T2DM group, and multivariate logistic regression showed that IBIL might be independent protective factors against insulin resistance (odds ratio (OR) = 0.602; 95% confidence interval (CI): 0.413–0.878; p=0.008). In cohort 2, at 1 month after metabolic surgery, serum bilirubin levels (TBIL, DBIL, and IBIL) increased, and the percentage change in IBIL was positively correlated with the change of the Matsuda Index (r = 0.195, p=0.045). Conclusions. The relationships between different types of bilirubin and insulin sensitivity varied. Serum indirect bilirubin might be a protective factor that enhances insulin sensitivity.

Objective Cardiometabolic diseases are the number one cause of mortality, accounting for over one third of all deaths in the United States. Cardiometabolic risk further increases with psychosocial stress exposure and during menopausal transition in women. Because disease risk and stress burden are associated with aberrant immune signaling, we hypothesized that responses of interleukin-6 (IL-6) to psychosocial stress may predict longitudinal cardiometabolic outcomes in perimenopausal women. Methods We conducted post hoc analyses in 151 perimenopausal or early postmenopausal women participants in a previously completed study. At study onset, participants underwent the Trier Social Stress Test (TSST), and plasma IL-6 was measured repeatedly before and during the 1 hour post-TSST. Subsequently, participants were randomly assigned to either hormonal treatment (HT) or placebo and followed for 12 months to determine longitudinal changes in cardiometabolic biomarkers. Results Greater IL-6 reactivity to stress, measured with baseline-adjusted area under the curve, predicted 12-month decrease in flow-mediated dilatation of the brachial artery (P = 0.0005), a measure of endothelial-dependent vascular function, but not in endothelial-independent function measured with nitroglycerin-mediated dilatation (P = 0.17). Greater baseline IL-6 levels predicted 12-month increase in insulin resistance based on the homeostatic model assessment of insulin resistance score (P = 0.0045) and in the number of criteria met for metabolic syndrome (P = 0.0008). These predictions were not moderated by HT. Conclusions Greater baseline IL-6 levels as well as its reactivity to stress may predict worsening in distinct cardiometabolic biomarkers as women transition to menopause. Interleukin-6 reactivity predicts decline in endothelial-dependent vascular function, whereas baseline IL-6 presages accumulation of metabolic risk.

AIM: The present study investigates gender dependent effects of insulin resistance on lipid profile and adipocytokines in individuals with diabetes receiving oral antidiabetic drugs (OADs). The aim was also to reveal the changes in the expression of genes involved in lipid metabolism and inflammation. METHODS: Lipid profile, adipocytokine levels and homeostatic model assessment of insulin resistance (HOMA-IR) was assessed in 100 patients with diabetes (M = 43, F = 57) matched for age and gender with healthy individuals (M = 45, F = 55). The expression pattern of genes was analyzed by quantitative real time PCR. RESULTS: Males consuming metformin with other drugs exhibited a positive association between HOMA-IR and cholesterol, triglyceride and very low density lipoprotein (VLDL). Females consuming only metformin and metformin with other drugs, showed a positive association of HOMA-IR with cholesterol and a negative association with adiponectin. In males and females with diabetes, a comparable expression of peroxisome proliferator activated receptor γ (PPARγ) while higher expression of sterol regulatory element binding protein 1 (SREBP1) was observed. Expression of fatty acid synthase (FAS), long chain acyl CoA Synthetases (ACSL), malonyl-CoA-acyl carrier protein transacylase (MCAT) and nuclear factor kappa β (NFkβ) was higher in men with diabetes than healthy males. Expression of tumor necrosis factor α (TNF-α) was higher in males and females with diabetes than respective healthy genders. CONCLUSION: Insulin resistance adversely affects lipid profile, adipocytokines in males with type 2 diabetes. Expression of genes involved in lipid metabolism and inflammation is found to be undesirably and differentially altered in both the genders.

There is little known about whether exposure to family poverty at specific periods of the early life course independently contributes to coronary heart disease risk beyond the contribution of concurrent poverty. Children were recruited in early pregnancy and additional survey data obtained during the pregnancy and at the 5-, 14- and 30-year follow-ups. Fasting blood samples were also obtained at the 30-year follow-up. Analyses are multinominal logistic regressions stratified by gender and with adjustments for confounding. For male offspring, family poverty at different stages of the early life course was not associated with measures of cardio-metabolic risk. For females early life course, poverty predicted obesity, homeostatic model assessment of insulin resistance (HOMA-IR) and total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), as well as concurrent family poverty associated with obesity, HOMA-IR, TC/HDL-C, HDL-C and increased systolic and diastolic blood pressure. Family poverty in the early life course independently predicts increased levels of cardio-metabolic risk of females. The primary finding, however, is that concurrent poverty is independently and strongly associated with increased cardio-metabolic risk levels in young adulthood.

Background Worldwide, the prevalence of insulin resistance ranges from 15.5 to 46.5%, among adults. Lebanon reported one of the highest rates reaching 44.6%. The literature suggests an association between dairy product consumption and insulin resistance, however results are inconclusive. To our knowledge, no study examined this association in the Middle Eastern Region. The aim of the study was to investigate the prevalence of insulin resistance among a sample of Lebanese adults, to identify its risk factors depending on gender, and to evaluate the association between insulin resistance and dairy products consumption. Methods A cross-sectional study was conducted among employees at Notre Dame University - Louaize. Four questionnaires were administered including a background and International Physical Activity Questionnaire short form questionnaires, food frequency questionnaire and a 24 h recall. Bioelectric Impedance Analysis (BIA) was used to measure percent body fat (PBF). Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was used to quantify insulin resistance. A person with HOMA-IR ≥ 2.5 was considered as insulin resistant. Statistical analyses were performed using the Statistical Package for Social Sciences version 23 for Windows. P Results Out of 286 study participants, 38.0% were insulin resistant. Average dairy product intake in the total sample was 2.2 ± 1.0 servings per day. Among males, the odds of having insulin resistance were 3.9 times higher (95%CI 1.4–11.0; p = 0.009) for those having a risky waist circumference compared to those having a healthy waist circumference. Among females, being married (OR: 0.2, 95%CI 0.1–0.5; p = 0.002), PBF (OR: 1.2, 95%CI 1.0–1.3; p = 0.008) and hypertriglyceridemia (OR: 8.7, 95%CI: 2.1–35.9; p = 0.003) were associated with HOMA-IR, after controlling for confounders. Dairy intake was not associated with HOMA-IR neither among males (p = 0.777), nor among females (p = 0.968), after controlling for confounders. Conclusion Dairy consumption was not associated with increased insulin resistance. More research focusing on the relationship between dairy intake and insulin resistance is needed, especially in the Arab and Middle-Eastern region. Future studies should examine the effect of different types of dairy products and the effect of different nutrients in dairy products on insulin resistance.

Background The objective of this study was to investigate the effects of Anethum graveolens (dill) powder supplementation on glycemic control, lipid profile, some antioxidants and inflammatory markers, and gastrointestinal symptoms in patients with type 2 diabetes. Materials and methods In this study, 42 patients with type 2 diabetes were randomly allocated to intervention and control groups and received either 3 g/day dill powder or placebo (3 capsules/day, 1 g each). Fasting blood sugar, insulin, homeostatic model assessment of insulin resistance, lipid profile, high-sensitivity C-reactive protein, total antioxidant capacity, malondialdehyde and gastrointestinal symptoms were measured in all of the subjects at baseline and postintervention. Results The dill powder supplementation significantly decreased the mean serum levels of insulin, homeostatic model assessment of insulin resistance, low-density lipoprotein cholesterol, total cholesterol and malondialdehyde in the intervention group in comparison with the baseline measurements (P P P = 0.01). The mean changes in insulin, low-density lipoprotein cholesterol, total cholesterol and malondialdehyde were significantly lower in the intervention group than in the control group (P P Conclusion Dill powder supplementation can be effective in controlling the glycemic, lipid, stress oxidative and gastrointestinal symptoms in patients with type 2 diabetes. Trial registration Iran Clinical Trials Registry: IRCT20120704010181N12. Registered on 12 May 2018.

BackgroundInflammation-related atherosclerotic peripheral vascular disease is a major end organ complication of diabetes mellitus that results in devastating morbidity and mortality. Extracellular vesicles (EVs) are nano-sized particles that contain molecular cargo and circulate in the blood. Here, we examined EV protein cargo from diabetic individuals and whether these EVs cause functional changes in endothelial cells.MethodsWe quantified inflammatory protein levels in plasma-derived EVs from a longitudinal cohort of euglycemic and diabetic individuals and used in vitro endothelial cell biological assays to assess the functional effects of these EVs with samples from a cross-sectional cohort.ResultsWe found several significant associations between EV inflammatory protein levels and diabetes status. The angiogenic factor, vascular endothelial growth factor A (VEGF-A), was associated with diabetes status in our longitudinal cohort. Those with diabetes mellitus had higher EV VEGF-A levels compared to euglycemic individuals. Additionally, EV levels of VEGF-A were significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-B). To test whether EVs with different inflammatory cargo can demonstrate different effects on endothelial cells, we performed cell migration and immunofluorescence assays. We observed that EVs from diabetic individuals increased cell lamellipodia formation and migration when compared to EVs from euglycemic individuals.ConclusionsHigher levels of inflammatory proteins were found in EVs from diabetic individuals. Our data implicate EVs as playing important roles in peripheral vascular disease that occur in individuals with diabetes mellitus and suggest that EVs may serve as an informative diagnostic tool for the disease.

OBJECTIVE: To assess the effect of low and high dose of glycyrrhizin on body weight, fasting blood sugar level (FBSL), serum insulin and glycemic indices in high fat diet induced type 2 diabetic rats. METHODS: In this experimental study with intervention period of 34 weeks, rats were grouped into four experimental groups; Group-A: normal control; Group-B: diabetic control; Group-C: glycyrrhizin-150 and Group-D: glycyrrhizin-300. Diabetes mellitus was induced in rats by giving high fat diet with injection dexamethasone. At 32 weeks, body weight, FBSL, serum insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Homeostatic Model Assessment of beta cells (HOMA-β) and Quantitative Insulin Sensitivity Check Index (QUICKI) were estimated. Two experimental groups received glycyrrhizin 150 mg/kg and 300 mg/kg per oral per day till completion of 34 weeks in addition to the high fat diet. At 34 weeks all the parameters were re-estimated. RESULTS: It was observed that both doses of glycyrrhizin significantly reduced FBSL and insulin levels in group-C (95.00±8.23 mg/dl, 671.60±55.51 µIU/ml) and group-D (94.00±6.27 mg/dl, 675.00±44.96 µIU/ml) as compared to group-B (236.10±13.26 mg/dl, 1052.80±37.82 µIU/ml) [p-value0.05) but significantly in group-D (293.20±42.54) as compared to group-B (372.00±24.03) [P-value

Objectives To describe the prevalence of healthy vascular aging (HVA), normal vascular aging and early vascular aging (EVA) in a sample of Spanish population without cardiovascular disease. The relationship of vascular aging with lifestyle, cardiovascular risk factors, psychological and inflammatory risk factors is also analyzed. Methods A total of 501 participants were recruited (49.70% men, aged 55.90 ± 14.24 years) by random sampling. Vascular aging was defined in three steps: Step 1: participants with vascular damage in carotid arteries or peripheral artery disease were classified as EVA. Step 2: with the percentiles of carotid-to-femoral pulse wave velocity (cfPWV) we used three criteria, first, the 10th and 90th cfPWV percentiles of the population studied by age and sex; second, the 10th and 90th percentiles of the European population reference values and third, the 25th and 75th cfPWV percentiles of the population studied by age and sex. Step 3: participants with hypertension or type 2 diabetes mellitus included in HVA were reclassified as normal vascular aging. Arterial stiffness was assessed with cfPWV using a Sphygmocor device. Physical activity was measured with an accelerometer. Psychological factors, lifestyle and other clinical information were obtained by standard questionnaire. Results The global prevalence of HVA was 8 and 14% (men 8 and 10%, women 9 and 18%), and 22 and 18% (men 26 and 23%, women 17 and 12%) for EVA, using criteria a and b, respectively. In the logistic regression analysis, vascular aging maintains positive associations with more sedentary time [odds ratio (OR) = 2.37 and 4.51], having triglycerides above 150 mg/dl (OR = 6.55 and 4.06), abdominal obesity (OR = 2.73 and 2.90), increased uric acid (OR = 4.63 and 2.98) and insulin resistance index homeostatic model assessment (OR = 4.05 and 6.78), and a negative association with less physical activity (OR = 0.29 and 0.28) using criteria a and b, respectively. Conclusion One in 10 has HVA and one in five EVA. The prevalence of EVA is higher in men. Study results suggest that preventive strategies aimed at increasing physical activity, reducing sedentary time and decreasing obesity and insulin resistance improve vascular aging.

Objective Childhood obesity linked to metabolic alterations, tend to appear simultaneously with altered adipocytokines, suggesting a role in pathogenetic development. Low circulating level of total and high molecular weight (HMW) adiponectin have been associated with components of the metabolic syndrome (MetS) and could represent an independent risk factor with potential use as a biomarker. To examine the prevalence of MetS in Mexican school children and to investigate the association of total and HMW adiponectin levels with biochemical parameters related to MetS. Methods The study included a population of boys and girls, from 8 to 11 years old. Anthropometric and biochemical parameters were evaluated according to weight and MetS status. A correlation analysis was fitted to establish an association between adiponectin concentrations and metabolic indicators. Results One-hundred and fifty five children participated (59.4% females) from 8-11 years of age. The prevalence of MetS was of 10.3%. Impaired biochemical parameters, including total and HMW adiponectin, were associated with obesity. The adiponectin level was significantly lower in MetS than in non-MetS subjects (4.5 vs. 5.4 μg/mL). Total- but not HMW adiponectin concentration was negatively correlated with blood pressure, fasting insulin, fasting blood sugar and Homeostatic Model Assessment for Insulin Resistance. Conclusion In young children, the total adiponectin level is associated with impaired biochemical parameters of carbohydrate metabolism and could be an excellent early predictor of metabolic complications.

Background Amaranth seed oil (ASO) and rapeseed oil (RSO) are functional foods that display antioxidant and hepatoprotective properties. These oils are also known to lower glucose and cholesterol levels. The current study compared the effects exerted by RSO and ASO on weight loss and metabolic parameters during a 3-week body mass reduction program. Methods Eighty-one obese subjects (BMI > 30 kg/m2), aged 25–70 years, were enrolled in a 3-week body mass reduction program based on a calorie-restricted diet and physical activity. Participants were randomly categorized into an AO group (administered 20 mL/d of ASO), a RO group (administered 20 mL/d of RSO), and a C group (control; untreated). Anthropometric and metabolic parameters were measured at baseline and endpoint. Results Significant decreases in weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), fat mass (FM), lean body mass (LBM), visceral fat mass (VFM), and total body water (TBW%) were observed in all groups (P P = 0.034), total cholesterol (Δ -14.6; P = 0.032), non-HDL cholesterol (Δ 15.9; P = 0.010), TG/HDL ratio (Δ -0.6; P = 0.032), LDL cholesterol (Δ -12.3; P = 0.042), and triglycerides (Δ -6.5; P = 0.000) were significantly improved in the AO group, compared to the RO group. Conclusions The 3-week body mass reduction intervention caused a significant reduction in the weight, BMI, WC, HC, FM, and VFM of all groups. Except for HOMA-IR, there were no statistical differences between the clinical parameters of all groups. However, a trend toward improved insulin levels and HDL% was noticeable in AO and RO. Therapies involving edible oils with high nutritional value, such as RSO and ASO, show potential for improving metabolic measurements during body mass reduction programs. Thus, obese patients undertaking weight reduction programs may benefit from RSO and ASO supplementation. Trial registration retrospectively registered, DRKS00017708.

Nahid Karamzad,1– 3 Esmaeil Faraji,4 Shaghayegh Adeli,2 Kristin Carson‐Chahhoud,5,6 Samaneh Azizi,2 Bahram Pourghassem Gargari2,3 1Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; 2Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; 3Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; 4Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 5Australian Centre for Precision Health, School of Health Sciences, University of South Australia, Adelaide, South Australia, Australia; 6School of Medicine, University of Adelaide, Adelaide, South Australia, AustraliaCorrespondence: Bahram Pourghassem GargariDepartment of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, IranEmail bahrampg@yahoo.comBackground: Type 2 diabetes mellitus (T2DM) is a prevalent disorder which accounts for 90– 95% of diabetic patients. The aim of this study was to assess the effects of menaquinone (MK-7) supplementation on glycemic indices, anthropometric indices and lipid profile, among patients with T2DM.Methods: In this double-blind placebo-controlled randomized clinical trial, 60 men and women with T2DM were allocated equally into either the MK-7 (200 μg/day) or the placebo group. Physical activity level and dietary intake were assessed using the international physical activity questionnaire-short form (IPAQ-SF) and a 3-day food record, pre- and post-intervention. Anthropometric measures, blood pressure, glycemic indices and lipid profile including fasting blood sugar (FBS), hemoglobin A1c (HBA1C), fasting insulin (FI), homeostatic model assessment insulin resistance index (HOMA-IR), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) were measured at baseline and after twelve weeks.Results: Forty-five patients completed the trial. There were no significant between-group differences for calorie intake, macronutrient intake, physical activity level or anthropometric measures at baseline and at the end of the study. Dietary vitamin K intake increased significantly at the end of the study in the MK-7 (p: 0.02) and placebo (p: 0.001) groups, but intergroup differences were not significant (p: 0.86). FBS (p: 0.01), HbA1c (p: 0.002), fasting insulin (p: 0.01) and HOMA-IR (p: 0.007) decreased significantly in the MK-7 group. Furthermore, after adjustment for the baseline values and changes of vitamin K intake at the end of study, FBS and HbA1C showed significant intergroup changes, and they were significantly lower in the MK-7 group compared to the placebo group. Lipid profile (TG, TC, LDL-C, HDL-C and LDL-C/HDL-C) did not change significantly within or between groups.Conclusion: MK-7 supplementation seems to be effective in the improvement of glycemic indices, but not the lipid profile of patients with T2DM.Clinical Trial Registration: The present study was prospectively registered at the Iranian Registry of Clinical Trials on May 2019 (ID: IRCT20100123003140N22).Keywords: diabetes, dyslipidemia, glycemic status, menaquinone, MK-7, phylloquinone, vitamin K, anthropometric indices

Insulin signaling is critical for neuroplasticity, cerebral metabolism as well as for systemic energy metabolism. In rodent studies, impaired brain insulin signaling with resultant insulin resistance (IR) modulates synaptic plasticity and the corresponding behavioral functions. Despite discoveries of central actions of insulin, in vivo molecular mechanisms of brain IR until recently have proven difficult to study in the human brain. In the current study, we leveraged recent technological advances in molecular biology and herein report an increased number of exosomes enriched for L1CAM, a marker predominantly expressed in the brain, in subjects with major depressive disorder (MDD) as compared with age- and sex-matched healthy controls (HC). We also report increased concentration of the insulin receptor substrate-1 (IRS-1) in L1CAM+ exosomes in subjects with MDD as compared with age- and sex-matched HC. We found a relationship between expression of IRS-1 in L1CAM+ exosomes and systemic IR as assessed by homeostatic model assessment of IR in HC, but not in subjects with MDD. The increased IRS-1 levels in L1CAM+ exosomes were greater in subjects with MDD and were associated with suicidality and anhedonia. Finally, our data suggested sex differences in serine-312 phosphorylation of IRS-1 in L1CAM+ exosomes in subjects with MDD. These findings provide a starting point for creating mechanistic framework of brain IR in further development of personalized medicine strategies to effectively treat MDD.

Backgrounds/Aims This study was done with the aim of assessing impact of surgery for chronic pancreatitis on exocrine and endocrine functions, quality of life and pain relief of patients. Methods 35 patients of chronic pancreatitis who underwent surgery were included. Exocrine function assessed with fecal fat globule estimation and endocrine function assessed with glycated haemoglobin (HbA1C), fasting plasma glucose (FPG), Insulin and C-peptide levels. Percentage (%) beta cell function by homeostatic model assessment (HOMA) was determined using web-based calculator. Quality of life (QOL) and pain assessment was done using Short form survey (SF-36) questionnaire and Izbicki scores respectively. Follow up done till 3 months following surgery. Results Endocrine insufficiency was noted in 13 (37%) patients in the postoperative period compared to 17 (49%) patients preoperatively (p=0.74). Exocrine insufficiency was detected in 11 (32%) patients postoperatively compared to 8 (23%) patients preoperatively, with denovo insufficiency noted in 3 (8%) patients (p

Background & aims Sedentariness and physical inactiveness are associated with deleterious health outcomes, but their associations with liver enzyme elevations remain uncertain. Methods In 10 385 US Hispanics/Latinos from the Hispanic Community Health Study/Study of Latinos, we examined associations of sedentary time and moderate-to-vigorous physical activity (MVPA) measured by accelerometers with liver enzyme elevations. Elevated alanine aminotransferase (ALT), aspartate aminotransferase and γ-glutamyltransferase (GGT) were defined as the highest gender-specific deciles. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated using weighted Poisson regressions. Results After adjusting for demographical/socioeconomic factors and MVPA, increasing quartiles of sedentary time were associated with a higher prevalence of elevated ALT (PRs [95% CI] = 1.0, 1.17 [0.92-1.47], 1.21 [0.96, 1.53] and 1.51 [1.13-2.02]; P-trend = .007) and elevated GGT (PRs [95% CI] = 1.0, 1.06 [0.82-1.36], 1.35 [1.06-1.73] and 1.66 [1.27-2.16]; P-trend = .0001). These associations were attenuated but remained significant after further adjustment for cardiometabolic traits including body-mass index, waist-hip-ratio, lipids and homeostatic model assessment of insulin resistance. In contrast, increasing quartiles of MVPA were associated with a lower prevalence of elevated ALT (PRs [95% CI] =1.0, 0.97 [0.77-1.23], 0.84 [0.66-1.06] and 0.72 [0.54-0.96]; P-trend = .01) after adjusting for demographical/socioeconomic factors and sedentary time, but this association became non-significant after further adjustment for cardiometabolic traits. Notably, the association of sedentary time with GGT elevation was significant both in individuals meeting the US Physical Activity Guidelines for Americans (MVPA ≥150 minutes/week) and in those who did not (both P-trend ≤ .003). Conclusions Our findings suggest that objectively measured sedentary time is independently associated with elevated ALT and GGT in US Hispanics/Latinos.

Context A person’s intrinsic metabolism, reflected in the metabolome, may describe the relationship between nutrient intake and metabolic health. Objectives Untargeted metabolomics was used to identify metabolites associated with metabolic health. Path analysis classified how habitual dietary intake influences body mass index z-score (BMIz) and insulin resistance (IR) through changes in the metabolome. Design Data on anthropometry, fasting metabolites, C-peptide, and dietary intake were collected from 108 girls and 98 boys aged 8 to 14 years. Sex-stratified linear regression identified metabolites associated with BMIz and homeostatic model assessment of IR using C-peptide (HOMA-CP), accounting for puberty, age, and muscle and fat area. Path analysis identified clusters of metabolites that underlie the relationship between energy-adjusted macronutrient intake with BMIz and HOMA-CP. Results Metabolites associated with BMIz include positive associations with diglycerides among girls and positive associations with branched chain and aromatic amino acids in boys. Intermediates in fatty acid metabolism, including medium-chain acylcarnitines (AC), were inversely associated with HOMA-CP. Carbohydrate intake is positively associated with HOMA-CP through decreases in levels of AC, products of β-oxidation. Approaching significance, fat intake is positively associated with HOMA-CP through increases in levels of dicarboxylic fatty acids, products of omega-oxidation. Conclusions This cross-sectional analysis suggests that IR in children is associated with reduced fatty acid oxidation capacity. When consuming more grams of fat, there is evidence for increased extramitochondrial fatty acid metabolism, while higher carbohydrate intake appears to lead to decreases in intermediates of β-oxidation. Thus, biomarkers of IR and mitochondrial oxidative capacity may depend on macronutrient intake.