Decreased Insulin Sensitivity Research Articles

Insulin Sensitizing and Antiatherogenic Role of Adiponectin: A Cross Sectional Study among the Healthy Subjects in Kerala

Background of the study and objectives: Adiponectin, the most abundantly secreted adipokine plays a central role in energy homeostasis. Different studies have reported the protective role of adiponectin in obesity related complications such as insulin resistance, hypertension, dyslipidemia, atherosclerosis etc. Since not much studies were conducted to analyze the role of adiponectin in the metabolic homeostasis among the healthy population in Kerala, we designed this study. Materials and methods: This study included 170 healthy subjects of both gender in the age group of 20-60 years. Anthropometric measurements and blood pressure were recorded. BMI, WHR and BF% were calculated. Fasting blood sample was used to measure glucose, lipid profile, insulin and adiponectin. HOMA-IR, HOMA-β and QUICKI were calculated. Data was analyzed by student’s ‘t’ test and pearson’s correlation analysis. p <0.05 was considered statistically significant. Results: Serum adiponectin showed a negative correlation with BMI (r=-0.583) and body fat percentage (r=-0.369). An inverse significant correlation of adiponectin with serum triglycerides (p=0.01), fasting glucose (p=0.01) and HOMA-IR (p=0.001) was observed. But insulin sensitivity (QUICKI) (p=0.001) and serum HDL-cholesterol (p=0.01) showed a significant positive correlation with adiponectin. Analysis of the study subjects based on BMI showed a significant decrease in serum adiponectin (p=0.001) among obese group in comparison with normal weight subjects. Hypoadiponectinemia among obese subjects was also found to be associated with insulin resistance and decreased insulin sensitivity expressed as QUICKI. Conclusion: Serum adiponectin showed a positive correlation with insulin sensitivity and HDL-cholesterol. Adiponectin retains a significant role as a mediator of insulin resistance and atherosclerosis.

Distribution of subcutaneous and intermuscular fatty tissue of the mid-thigh measured by MRI-A putative indicator of serum adiponectin level and individual factors of cardio-metabolic risk.

Obesity and metabolic syndrome (MetS) are associated with hypoadiponectinemia. On the contrary, studies revealed correlations between the amount of subcutaneous adipose tissue (SAT) and higher serum adiponectin levels. Furthermore, independent association of intermuscular adipose tissue (IMAT) deposit in the thigh with cardiometabolic risk factors (including total blood cholesterol, low-density lipoprotein (LDL), and triglycerides), and decreased insulin sensitivity, as MetS components, are sufficiently described. The combined relationship of thigh IMAT and SAT with serum adiponectin, leptin levels, and cardiometabolic risk factors have not been investigated till date. Since both SAT and IMAT play a role in fat metabolism, we hypothesized that the distribution pattern of SAT and IMAT in the mid-thigh might be related to adiponectin, leptin levels, and serum lipid parameters. We performed adipose tissue quantification using magnetic resonance imaging (MRI) of the mid-thigh in 156 healthy volunteers (78 male/78 female). Laboratory measurements of lipid panel, serum adiponectin, and leptin levels were conducted. Total serum adiponectin level showed a significant correlation with the percentage of SAT of the total thigh adipose tissue (SAT/ (IMAT+SAT)) for the whole study population and in sex-specific analysis. Additionally, SAT/(IMAT+SAT) was negatively correlated with known cardiometabolic risk factors such as elevated total blood cholesterol, LDL, and triglycerides; but positively correlated with serum high-density lipoprotein. In multiple linear regression analysis, (SAT/(IMAT+SAT)) was the most strongly associated variable with adiponectin. Interestingly, leptin levels did not show a significant correlation with this ratio. Adipose tissue distribution in the mid-thigh is not only associated to serum adiponectin levels, independent of sex. This proposed quantitative parameter for adipose tissue distribution could be an indicator for individual factors of a person`s cardiometabolic risk and serve as additional non-invasive imaging marker to ensure the success of lifestyle interventions.

Parents' cardiovascular risk factors are related to overweight and obesity in young Brazilians with type 1 diabetes

AimTo identify family background characteristics and cardiovascular disease (CVD) risk factors linked to overweight and obesity in Brazilian with type 1 diabetes (T1D). MethodsWe performed cross-sectional anthropometric and laboratory analyses in young individuals with T1D. ResultsAmong 181 participants, 87 were women and 94 were men (64%/78% normal weight, 27%/15% overweight and 9%/7% obese). Obese men were older; were more likely to be Black; had higher triglyceride levels and diastolic blood pressure (BP), lower estimated glucose disposal rate (eGDR) and higher prevalence of first-degree relatives (FDR) with hypertension and early CVD. Overweight and obese women were more likely to have lower eGDR, and obese women were more likely to have FDR with obesity. ConclusionOne third of young people with T1D were overweight or obese. Excess weight was associated with family history (FH) of obesity for women and FH of early CVD or hypertension for men. BMI was related to decreased insulin sensitivity in both genders, but only men with T1D had metabolic impairment. Our data highlight the importance of considering family background in individuals with T1D.

Alleviation of Neuronal Cell Death and Memory Deficit with Chungkookjang Made with Bacillus amyloliquefaciens and Bacillus subtilis Potentially through Promoting Gut-Brain Axis in Artery-Occluded Gerbils.

Short-term fermented soybeans (chungkookjang) with specific Bacillus (B.) spp. have anti-obesity, antidiabetic, and anti-stroke functions. We examined the hypothesis that the long-term consumption of B. amyloliquefaciens SCGB 1 fermented (CKJ1) and B. subtilis SCDB 291 (CKJ291) chungkookjang can alleviate clinical symptoms and hyperglycemia after ischemic stroke by promoting the gut microbiota–brain axis. We examined this hypothesis in Mongolian male gerbils with stroke symptoms induced by carotid artery occlusion. The artery-occluded gerbils were divided into five groups: no supplementation (Control, Normal-control), 4% cooked soybeans (CSB), CKJ1, or CKJ291 in a high-fat diet for 3 weeks. The carotid arteries of gerbils in the Control, CSB, CKJ1, and CKJ291 groups were occluded for 8 min and they then continued on their assigned diets for an additional 3 weeks. Normal-control gerbils had no artery occlusion. The diets in all groups contained an identical macronutrient composition using starch, casein, soybean oil, and dietary fiber. The CSB, CKJ1, and CKJ291 groups exhibited less neuronal cell death than the Control group, while the CKJ1 group produced the most significant reduction among all groups, as much as 85% of the Normal-control group. CKJ1 and CKJ291 increased the blood flow and removal of blood clots, as determined by Doppler, more than the Control. They also showed more improvement in neurological disorders from ischemic stroke. Their improvement showed a similar tendency as neuronal cell death. CKJ1 treatment improved memory impairment, measured with Y maze and passive avoidance tests, similar to the Normal-control. The gerbils in the Control group had post-stroke hyperglycemia due to decreased insulin sensitivity and β-cell function and mass; the CKJ291, CSB, and CKJ1 treatments protected against glucose disturbance after artery occlusion and were similar to the Normal-control. CKJ1 and CKJ291 also reduced serum tumor necrosis factor-α concentrations and hippocampal interleukin-1β expression levels, compared to the Control. CKJ1 and CKJ291 increased the contents of Lactobacillus, Bacillus, and Akkermansia in the cecum feces, similar to the Normal-control. Picrust2 analysis showed that CKJ1 and CKJ291 increased the propionate and butyrate metabolism and the starch and glucose metabolism but reduced the lipopolysaccharide biosynthesis and fatty acid metabolism compared to the Control. In conclusion, daily CKJ1 and CKJ291 intake prevented neuronal cell death and memory dysfunction from the artery occlusion by increasing blood flow and β-cell survival and reducing post-stroke-hyperglycemia through modulating the gut microbiome composition and metabolites to influence the host metabolism, especially inflammation and insulin resistance, protecting against neuronal cell death and brain dysfunction. CKJ1 had better effects than CKJ291.

Modeling the variability of insulin sensitivity during the menstrual cycle in women with type 1 diabetes to adjust open-loop insulin therapy.

Women with type 1 diabetes (T1D) typically experience a decrease in insulin sensitivity (SI) during the second half of their menstrual cycle (or the luteal phase (LP)), which oftentimes is not properly addressed by insulin therapy, therefore leading to increased exposure to hyperglycemia. This study proposes a suitable way to model SI variability due to the menstrual cycle in the FDA-accepted University of Virginia (UVA)/Padova T1D Simulator, to determine to what extent the inclusion of menstrual cycle information to fine-tune insulin therapy could help improve glycemic control in the LP of the menstrual cycle. In-silico tests were performed considering different simulation scenarios, and the obtained results show that hyperglycemic excursions can be largely reduced when SI variability is taken into account for planning insulin therapy, without a relevant increase in hypoglycemic events.

In vitro study of Cratoxylum glaucumStem ethyl acetate extract as antidiabetic

Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to decreased insulin secretion, or decreased insulin sensitivity, or both. If insulin is not available or the amount is low, then glucose cannot enter the cells and will continue to be in the bloodstream. DM can cause chronic complications such as eye complications, skin infections and stroke. DM treatment takes a long time by using synthetic drugs that will cause side effects, therefore the search for herbal-based drugs is the community’s choice. Idat plant (Cratoxylum glaucum) is a local plant from Bangka Belitung. Several studies on the genus Cratoxylum from China and Thailand showed a very high inhibitory ability against the inhibition of a-glucosidase enzymes, protein tyrosine phosphate, and carbohydrate hydrolysis enzymes because they contain phenolic compounds anthraquinones and xanthones. Therefore, the importance of more intensive research on C. glaucum species regarding the content of secondary metabolites in C. glaucum stems and their antidiabetic power. The extraction method in this research is maceration with ethyl acetate solvent. Qualitative examination of phenolic and flavonoid content using reagents, as well as antidiabetic testing was carried out in vitro with dengan α-glucosidase enzyme inhibition method. Based on qualitative testing of phenolic and flavonoid compounds, the content of these compounds was obtained. antidiabetic test showed that the-glucosidase inhibitor of ethyl acetate extract had very strong activity with an IC50 of 4.21 g/mL. Therefore, the stem of the idat plant can be used as a therapy for the treatment of diabetes mellitus.

Transcription factor EB enhances autophagy and ameliorates palmitate-induced insulin resistance at least partly via upregulating AMPK activity in skeletal muscle cells.

This study aimed to elucidate the role of transcription factor EB (TFEB) in protecting C2C12myotubes against palmitate (PA)-induced insulin resistance (IR) and explored its mechanism associated with autophagy. PA treatment significantly decreased insulin sensitivity in myotubes and downregulated TFEB protein expression. TFEB overexpression significantly reversed the PA-suppressed glucose transporter 4 (GLUT4) protein expression and improved intracellular glucose uptake and consumption, and also alleviated the decrease of autophagy markers induced by PA. The effect of TFEB overexpression on GLUT4 was also abolished by the autophagy inhibitor 3-MA. In addition, AMPKɑ2-DN inhibited or abolished the effects of TFEB overexpression on upregulation of GLUT4 and PA-induced decrease of autophagy marker expressions. Taken together, our data demonstrated that upregulation of TFEB improved PA-induced IR in C2C12myotubes by enhancing autophagy and upregulating AMPK activity. TFEB, as a critical regulator of glucose homeostasis in skeletal muscle cells, may be a potential therapeutic target for IR and Type 2 diabetes.

PSVII-18 Association of post-absorptive glucose and acetate metabolism with feed intake, growth, and efficiency in finishing beef heifers

Abstract Glucose and acetate are important nutrients for muscle and fat accretion in beef cattle. The objective of this experiment was to determine if the demand for acetate and glucose, as well as insulin response to glucose, are associated with dry matter intake (DMI), average daily gain (ADG), residual feed intake (RFI), and gain:feed (G:F). Charolais heifers (n = 16; initial BW = 412 ± 10 kg) were trained to close human contact and fed a finishing diet ad libitum in an Insentec feeding system. Following a 12-hour fast, a jugular catheter was inserted, and an acetate clearance test was performed by infusing acetate (2.18 mmol/kg BW0.75) and collecting blood samples over a 30-minute period. One hour after the conclusion of the acetate test, a glucose clearance test was performed by infusing glucose (7.57 mmol/kg BW0.75) and collecting samples over a two-hour period. Four days after the metabolic tests, heifers began an 84-d DMI and ADG test period. The area under the acetate, glucose, and insulin curves were calculated as were the clearance rate, peaks, nadir, and insulin time to peak. Pearson correlations were calculated for the metabolic parameters and production traits using SAS 9.4. Heifers gained 1.69 ± 0.03 kg/d and consumed 10.4 ± 0.19 kg/d. Acetate and glucose clearance rates were not associated with any production trait (P > 0.40). Insulin time to peak concentration after the glucose challenge was associated (r = 0.69; P = 0.003) with G:F, but peak concentration was not (P = 0.45). Additionally, there was a trend (r = 0.40; P = 0.13) for area under the insulin curve to be associated with G:F. Given the small sample size in this experiment, it is possible that decreased insulin sensitivity early in the finishing period is related to improved feed efficiency in finishing heifers.

Poor In Utero Growth, and Reduced β-Cell Compensation and High Fasting Glucose From Childhood, Are Harbingers of Glucose Intolerance in Young Indians.

India is a double world capital of early-life undernutrition and type 2 diabetes. We aimed to characterize life course growth and metabolic trajectories in those developing glucose intolerance as young adults in the Pune Maternal Nutrition Study (PMNS). PMNS is a community-based intergenerational birth cohort established in 1993, with serial information on parents and children through pregnancy, childhood, and adolescence. We compared normal glucose-tolerant and glucose-intolerant participants for serial growth, estimates of insulin sensitivity and secretion (HOMA and dynamic indices), and β-cell compensation accounting for prevailing insulin sensitivity. At 18 years (N = 619), 37% of men and 20% of women were glucose intolerant (prediabetes n = 184; diabetes n = 1) despite 48% being underweight (BMI <18.5 kg/m2). Glucose-intolerant participants had higher fasting glucose from childhood. Mothers of glucose-intolerant participants had higher glycemia in pregnancy. Glucose-intolerant participants were shorter at birth. Insulin sensitivity decreased with age in all participants, and those with glucose intolerance had consistently lower compensatory insulin secretion from childhood. Participants in the highest quintile of fasting glucose at 6 and 12 years had 2.5- and 4.0-fold higher risks, respectively, of 18-year glucose intolerance; this finding was replicated in two other cohorts. Inadequate compensatory insulin secretory response to decreasing insulin sensitivity in early life is the major pathophysiology underlying glucose intolerance in thin rural Indians. Smaller birth size, maternal pregnancy hyperglycemia, and higher glycemia from childhood herald future glucose intolerance, mandating a strategy for diabetes prevention from early life, preferably intergenerationally.

Association of Genetic Polymorphism in Apolipoprotein A5 and Lipoprotein Lipase Genes with Type Ii Diabetes Mellitus Patients in Rural South Western Maharashtra

The most commonly found type of diabetes in India is type II diabetes mellitus (T2DM), which is characterized by decrease in insulin secretion and decrease in insulin sensitivity. Several environmental factors, genetic factors, socio-economic factors, life style, dietary habits have contributed to the surge of T2DM cases in India. Numerous genes involved in lipid metabolism are likely to be candidates as the markers for obesity and T2DM. In the present study, single nucleotide polymorphism (SNP) of two genes namely Apolipoprotein A5 (APOA5) and Lipoprotein lipase (LPL) involved in triglyceride metabolism were investigated using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). The control group comprised of non-obese, non-diabetic subjects (n=120) and T2DM cases were divided into obese (n=120), and non-obese (n=120) groups based on their body mass index (BMI). The demographic features between the control and cases were compared using Chi-square distribution. The genotype frequencies of control and cases were compared using analysis of variance (ANOVA) and binary logistic regression analysis (Odds’ ratio (OR) and adjusted Odds’ ratio). It was observed that APOA5 rs3135506 (OR = 0.46 (0.27-0.79); p = 0.007) was negatively associated, while APOA5 rs662799 (OR = 2.22 (1.28-3.84); p = 0.006) was significantly associated in non-obese diabetic patients. APOA5 rs3135506 (OR = 0.03 (0.01-0.06); p &lt; 0.001) was negatively associated and rs662799 (OR = 4.68 (1.47-14.93); p = 0.01) was significantly associated in obese diabetic patients. Both LPL SNPs (rs285 and rs320) were found not to be associated with T2DM. The association of Apo A5 variants with T2DM may be because of post transcriptional inhibition leading to reduced Apo A5 expression or these alleles may be in linkage disequilibrium with alleles which directly affect the functioning of APOA5. The observations indicated that T2DM is a multi-factorial disease with a large number of gene-gene and gene-environment interactions.

Assessment of Insulin Secretion and Insulin Resistance in Human.

The impaired insulin secretion and increased insulin resistance (or decreased insulin sensitivity) play a major role in the pathogenesis of all types of diabetes mellitus (DM). It is very important to assess the pancreatic β-cell function and insulin resistance/sensitivity to determine the type of DM and to plan an optimal management and prevention strategy for DM. So far, various methods and indices have been developed to assess the β-cell function and insulin resistance/sensitivity based on static, dynamic test and calculation of their results. In fact, since the metabolism of glucose and insulin is made through a complex process related with various stimuli in several tissues, it is difficult to fully reflect the real physiology. In order to solve the theoretical and practical difficulties, research on new index is still in progress. Also, it is important to select the appropriate method and index for the purpose of use and clinical situation. This review summarized a variety of traditional methods and indices to evaluate pancreatic β-cell function and insulin resistance/sensitivity and introduced novel indices.

Pancreatic β-Cell Dysfunction Is Associated with Nonalcoholic Fatty Liver Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with decreased insulin sensitivity. However, the association between NAFLD and pancreatic β-cell function is still ambiguous. Here, we assessed whether pancreatic β-cell function is associated with NAFLD. Method: The data of NHANES III from 1988 to 1994 were used. NAFLD was diagnosed when subjects had ultrasonographically hepatic steatosis without other liver diseases. Disposition index (DI) was employed to assess pancreatic β-cell function. A total of 6168 participants were included in this study. Results: NAFLD participants had much higher HOMA2-%B (weighted mean, 124.1; standard error, 1.8) than the non-NAFLD participants (weighted mean, 100.7; standard error, 0.9). However, when evaluating the β-cell function in the context of insulin resistance by using DI index, DI levels were much lower in NAFLD subjects (weighted mean, 79.5; standard error, 1.0) compared to non-NAFLD (weighted mean, 95.0; standard error, 0.8). Multivariate logistic regression analyses showed that DI was inversely associated with NAFLD prevalence. The adjusted OR (95% CI) for quartile 1 versus quartile 4 was 1.81 (1.31–2.50) (p < 0.001 for trend). Moreover, DI was also inversely associated with the presence of moderate to severe hepatic steatosis. The multivariable-adjusted ORs across quartiles of DI were 2.47, 1.44, 0.96 and 1.00 for the presence of moderate to severe hepatic steatosis (p < 0.001 for trend). Conclusions: Pancreatic β-cell function might be a new predictor for the presence of NAFLD, and insufficient compensatory β-cell function is associated with NAFLD.

Role of 14-3-3β protein on ovarian folliculogenesis, steroidogenesis and its correlation in the pathogenesis of PCOS in mice

This study was designed to assess for the first time the circulating and ovarian level of 14-3-3β protein in the PCOS mice and the possible correlation between 14-3-3β protein with PCOS related increase in testosterone (HA), insulin levels (HI) and reduced insulin sensitivity in the ovary. PCOS was induced in mice using treatment of letrozole (by oral gavage) for 21 days. Immunohistochemical study showed increased expression of 14-3-3β protein in PCOS ovary compared to the control ovary. The circulating testosterone and insulin levels, together with circulating and ovarian levels of 14-3-3β protein also showed significant increase in PCOS mice compared to the control mice. An increase in 14-3-3β protein was observed positively correlated with circulating testosterone and insulin levels but showed a negative correlation with ovarian expression of insulin receptor protein in PCOS mice. The treatment of 14-3-3β protein in vitro to the normal ovary showed a significant increase in testosterone synthesis but a significant decline in insulin receptor protein expression compared to the vehicle-treated ovary of adult mice. The present study showed the direct role of 14-3-3β protein in increasing testosterone synthesis along with decreasing insulin sensitivity. Thus, 14-3-3β protein may be playing possible role in PCOS pathogenesis.

Faktor-faktor yang berhubungan dengan kejadian diabetes mellitus tipe-II pada pasien rawat jalan

Background: Diabetes Mellitus (DM) occurs due to hyperglycemia, abnormalities in carbohydrate, protein, and fat metabolism caused by decreased insulin secretion, or decreased insulin sensitivity or both, causing chronic microvascular, macrovascular, and neuropathic complications. Aceh ranks 8th in the prevalence of diabetes mellitus from all provinces in Indonesia at 2.6% and the national prevalence is 2.1%.Objective: This study aims to determine the factors associated with the incidence of type-II diabetes mellitus in outpatients.Methods: An analytical observational study with a cross-sectional design was conducted in 2019 in Banda Aceh. The sampling method is purposive sampling with a total of 96 samples, outpatients at the Meuraxa Hospital. Data collection that has been carried out includes data on age, gender, genetics, obesity, and diet. Chi-square test data analysis at 95% CI.Results: The results of this study have shown that people who are over 43 years of age suffer from type-II diabetes mellitus and people who are obese, have genetics, and have poor diet can suffer from type-II diabetes mellitus. There was a significant relationship between age, genetics, obesity, and diet with the incidence of type-II diabetes mellitus (p &lt; 0.05), while gender did not have a significant relationship with the incidence of diabetes mellitus (p &gt; 0.05).Conclusion: Obesity in patients with type II diabetes is age, genetic factors, and diet. Suggestion, it is necessary to continue counseling related to the causes of type-II diabetes mellitus in patients who visit the hospital.

Syndrome Metabolic Markers, Fitness and Body Fat Is Associated with Sleep Quality in Women with Severe/Morbid Obesity.

Background: Sleep is an important modulator of neuroendocrine function and glucose metabolism. Poor sleep quality is related to metabolic and endocrine alterations, including decreased glucose tolerance, decreased insulin sensitivity, and increased hunger and appetite. Objective: The aim of the present study was to determine the association between sleep quality with metabolic syndrome (MetS) markers, fitness and body fat of women with severe/morbid obesity. Methods: This cross-sectional study included 26 women with severe/morbid obesity. Fasting plasma glucose (FPG), high-density lipids (HDL-c), triglycerides (TGs), and the metabolic outcomes total cholesterol (Tc) and low-density lipids (LDL-c), systolic (SBP) and diastolic blood pressure (DBP), body composition and fitness were measured. Results: Poor sleep quality showed a positive association with body fat (%) ≥ 48.2 (OR; 8.39, 95% CI; 1.13–62.14, p = 0.037), morbid obesity (OR; 8.44, 95% CI; 1.15–66.0, p = 0.036), glucose ≥ 100 mg/dL (OR; 8.44, 95% CI; 1.15–66.0, p = 0.036) and relative handgrip strength ≤ 0.66 (OR; 12.2, 95% CI; 1.79–83.09, p = 0.011). Conclusion: sleep quality is associated with health markers in women with severe/morbid obesity.

Peripheral Insulin Resistance Is Associated with Copeptin in Patients with Chronic Kidney Disease.

Insulin resistance is associated with cardiovascular disease risk and worsened kidney function. Patients with CKD have higher levels of insulin resistance. Elevated levels of copeptin (a surrogate for vasopressin levels) have been associated with an increased incidence and progression of CKD, and with incident diabetes mellitus. The purpose of our study was to examine the relationship between insulin resistance, copeptin, and CKD. We performed a cross-sectional study to investigate if insulin resistance was associated with higher copeptin levels in nondiabetic patients with stage 3-4 CKD versus controls. We measured plasma copeptin levels and used data from 52 patients with stage 3-4 CKD and 85 controls (eGFR ≥60 ml/min per 1.73 m2) enrolled in the Insulin Resistance in Chronic Kidney Disease (IRCKD) study. We then used a multivariable linear-regression model to assess the independent relationship between peripheral or hepatic insulin resistance and copeptin across levels of eGFR. We found that in patients with CKD (eGFR of 30-60 ml/min per 1.73 m2), but not in controls, peripheral insulin resistance was significantly correlated with higher levels of log copeptin (r=-0.21, P=0.04). In patients with CKD, when adjusted for age, sex, BMI, serum osmolality, log IL6, and log leptin/adiponectin ratio, each 1 SD decrease in insulin sensitivity was associated with a 39% increase in serum copeptin levels. The relationship between hepatic insulin resistance, copeptin, and eGFR is similar between controls and patients with reduced eGFR. Peripheral insulin resistance is associated with elevated copeptin levels in nondiabetic patients with stage 3-4 CKD. Further research into how the interaction between peripheral insulin resistance and elevated vasopressin affects CKD progression could be of interest.

Weight Change in Post-Menopausal Women with Breast Cancer during Chemotherapy-Perspectives on Nutrition, Activity and Bone Metabolism: An Interim Analysis of a 5-Year Prospective Cohort.

Women with breast cancer are a growing population due to improved screening and treatment. It has been described that chemotherapy can negatively affect patients’ metabolism. The aim of this study is to assess weight gain during chemotherapy treatment in an interim analysis on an ongoing prospective cohort of women with early breast cancer. To help untangle the many possible reasons for weight change, we examine blood tests, Patient-Reported Outcomes (PROs), and bone mineral density (BMD). We find that the 38 women that have measurements taken after chemotherapy have an average weight gain of 1.2 kg although not significant. Together with this, there is a significant drop in HDL cholesterol, an increase in triglycerides, and a non-significant tendency towards decreased insulin sensitivity. PROs show that although the women experience more pain and fatigue, they have higher activity levels. BMD is at an expected level according to age. All in all, we see an increased focus on physical activity and nutrition, leading to less severe metabolic changes as previously reported. However, even though more measures are taken, we still see an overall negative metabolic impact with unknown long-term implications.

Estimation of Fluoride and Sirtuin1 in Patients with Diabetic Nephropathy in Kolar District of Karnataka, India.

Objective Prevalence of type-2 diabetes mellitus (DM) and diabetic nephropathy is growing rapidly in Asian countries, affecting low- and middle-income groups. One of the epidemiological issues of Kolar district is fluorosis; advanced glycation end product, carboxymethyl lysine (CML), and a molecule of interest Sirtuin1 are employed in the present study. In the correlation of fluoride with sirtuin1and CML with sirtuin1 of cases lies the important rationale of the study to assess the extent of kidney damage. Materials and Methods This is a comparative cross-sectional study with three groups, each with 70 patients, as follows: G1, control; G2, diabetes with diabetic nephropathy; and G3, type-2 DM without any complications. Informed written consent was obtained from all study patients. All the routine investigations were performed by fully automated Vitro 5, 1 Fs, Vitros. Fasting insulin was analyzed by Vitro eCI and glycated hemoglobin was estimated by BioRad D10. Sirtuin1, CML, and fructosamine were estimated by double antibody sandwich technique. Statistical Analysis The statistical analysis was performed by SPSS 20 (IBM) software. Means of normally distributed data were compared using analysis of variance (ANOVA), and not normally distributed data were compared by Kruskal–Wallis test. A p -value of less than 0.05 was considered statistically significant. Results A decrease in sirtuin1, serum, and urine fluoride of group 2 (34.74 [25.08–53.2], 0.24 [0.2–0.5], and 0.24 [0.16–0.41]) was observed compared with other groups. Increased CML and fluoride act as prooxidant, restricting the effect of sirtuin1 on cellular damage, causing further complications such as increased insulin resistance and decreased insulin sensitivity. Conclusion The alterations in serum sirtuin1 levels indicate the severity of damage due to stress during hyperglycemia and fluoride toxicity; hence, sirtuin1 can be considered as biomarker of aging. Subsequently, the correlation of CML, estimated glomerular filtration rate (eGFR), and fluoride with sirtuin1 indicates that increasing sirtuin1 may defend the forthcoming damage and could be considered in therapeutics.

Interaction of dietary carbohydrate and fat on glucose metabolism in growing pigs

Increased consumption of fructose has been suggested to be a contributing cause of the increased rates of obesity in humans. Rodent studies have shown an increase in de novo lipogenesis and decreased insulin sensitivity in response to feeding high levels of fructose, but it is unclear if these effects occur in the same progression in humans. We aimed to develop a swine model for studying changes in glucose metabolism and insulin resistance resulting from dietary carbohydrate alone or in combination with high dietary fat. Two experiments were conducted to determine if the source of dietary carbohydrate, with or without added fat, had an effect on body weight gain, glucose metabolism, or insulin response in growing pigs. In the first experiment, pigs (24 barrows, initial body weight 28 kg) were fed one of 4 diets in which the source of carbohydrate was varied: 1) 20% starch; 2) 10% glucose + 10% starch; 3) 10% fructose + 10% starch; and 4) 20% fructose for 9 weeks. There were no differences in growth rate or glucose clearance observed. Experiment 2 was conducted as a 3 × 2 factorial with the main effects of carbohydrate source (20% starch, glucose, or fructose) and added fat level (0 vs 10%). Pigs (24 barrows, initial body weight 71 kg) were fed one of 6 experimental diets for 9 weeks. Compared to the other dietary treatments, pigs fed fructose with high fat had an elevated glucose area under the curve during the GTT (Carbohydrate x Fat interaction, P < 0.01). This same group had a lower insulin response (Carbohydrate x Fat, P < 0.05). This work demonstrates that pigs can be a viable model to assess the long-term effects of dietary carbohydrates on metabolism and body composition. Studies of longer duration are needed to determine if these changes are indicative of insulin resistance.

MiR-302 Attenuates Mutant Huntingtin-Induced Cytotoxicity through Restoration of Autophagy and Insulin Sensitivity.

Huntington’s disease (HD) is an autosomal-dominant brain disorder caused by mutant huntingtin (mHtt). Although the detailed mechanisms remain unclear, the mutational expansion of polyglutamine in mHtt is proposed to induce protein aggregates and neuronal toxicity. Previous studies have shown that the decreased insulin sensitivity is closely related to mHtt-associated impairments in HD patients. However, how mHtt interferes with insulin signaling in neurons is still unknown. In the present study, we used a HD cell model to demonstrate that the miR-302 cluster, an embryonic stem cell-specific polycistronic miRNA, is significantly downregulated in mHtt-Q74-overexpressing neuronal cells. On the contrary, restoration of miR-302 cluster was shown to attenuate mHtt-induced cytotoxicity by improving insulin sensitivity, leading to a reduction of mHtt aggregates through the enhancement of autophagy. In addition, miR-302 also promoted mitophagy and stimulated Sirt1/AMPK-PGC1α pathway thereby preserving mitochondrial function. Taken together, these results highlight the potential role of miR-302 cluster in neuronal cells, and provide a novel mechanism for mHtt-impaired insulin signaling in the pathogenesis of HD.