Fasting Plasma Insulin Levels Research Articles

Incorporation of Unique, Diet-derived Fatty Acids into Hepatic Tissue Is Associated with Improved Glucose Homeostasis in Aged CD-1 Mice (OR24-02-19)

ObjectivesWe hypothesized that the chronic consumption of unique dietary FA derived from dairy fat and echium oil, respectively, would affect the FA composition and content of the hepatic tissue and correlate with parameters of glucose homeostasis in an aged, genetically heterogeneous mouse population. Our objectives were to i) measure glucose homeostasis, ii) determine the FA composition of hepatic tissue, and iii) correlate physiologic data and hepatic FA content by diet and sex. MethodsFrom one month of age, CD-1 male and female mice (n = 10/diet/sex) were fed either a high-fat (40% total energy) control diet comprising of the FA composition of the typical U.S. American diet (CO), or an isoenergetic diet with 30% of CO fat replaced with dairy fat (BO) or echium oil (EO) for the study duration of 13 months. Every three months, whole-body glucose homeostasis was assessed (i.e., glucose tolerance and insulin tolerance tests (GTT and ITT, respectively)). At the end of the study, hepatic tissue was collected and analyzed for FA composition via gas-liquid chromatography. ResultsHepatic content of stearidonic acid (SDA; 18:4 n-3) and γ-linolenic acid (18:3 n-6) was greatest in EO-fed mice (P < .0001). Mice fed a BO-diet had the greatest hepatic content of total odd- and branched-chain FA (OBCFA) and conjugated linoleic acids (P < .0001), as well as a greater hepatic content of 18:1 isomers compared to EO-fed mice (P < .001). In EO-fed females, hepatic content of SDA correlated with improved glucose tolerance, as determined by GTT area under the curve (r = –.94; P < 0.01), and in EO-fed males, hepatic content of SDA was positively associated with improved insulin sensitivity (r = .79; P < 0.05). In BO-fed males, hepatic content of total OCFA was negatively correlated with fasting plasma insulin levels (r = –.83; P < 0.05), and hepatic content of total iso BCFA was associated with improved insulin sensitivity (r = –.89; P < 0.05). ConclusionsThese findings demonstrate that habitual consumption of unique FA derived from dairy fat and echium oil influences hepatic FA composition and content and correlates with improvements in whole-body glucose homeostasis in an aged population. Furthermore, this study suggests that dietary fat quality may be part of an effective preventative strategy for metabolic diseases such as T2D in the elderly. Funding SourcesArmin Grams Memorial Research Award, UVM Robert Larner, M.D. College of Medicine; USDA-NIFA Hatch Fund (accession number: 1006628).

1881-P: The SGLT2 Inhibitor Dapagliflozin Improves Glucose Control and Enhances Liver Fatty Acid Oxidation and Ketone Body Formation in Insulin Resistant Obese Zucker Rats

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are effective treatments for improving glucose control and reducing cardiovascular events in patients with T2D. In the present study we examined the metabolic effects of chronic treatment of the SGLT2i dapagliflozin in obese insulin resistant Zucker rats. Three different studies were performed with the aims to assess: 1) liver CoA intermediates, 2) whole-body FA metabolism using a constant infusion of 3H-palmitate and 3) tissue-specific rates of FA utilization and storage using 3H-labelled bromo-palmitate and 14C-labelled palmitate, respectively. Four weeks treatment with dapagliflozin (1 mg/kg/d p.o.) markedly increased glucosuria, reduced HbA1c and fasting plasma glucose and insulin levels and increased pancreatic insulin content compared to vehicle treated rats. Liver acetyl-CoA levels were increased while the malonyl-CoA/acetyl-CoA ratio was decreased following dapagliflozin treatment, suggestive of an increased liver FA oxidation. Treatment with dapagliflozin also increased liver HMG-CoA levels, an intermediate in ketone body formation, indicating that the acetyl-CoA is diverted to ketone body formation. This was supported by increased fasting plasma levels of the ketone body β-hydroxybutyrate in the dapagliflozin-treated rats compared to vehicle. Dapagliflozin treatment resulted in increased plasma FA levels and rates of whole-body FA oxidation. The increased whole-body FA oxidation was subsequently found to be driven by an increase in liver FA utilization. In conclusion, dapagliflozin improves glucose homeostasis and enhances FA utilization in insulin resistant obese animals. These results suggest that dapagliflozin-induced glucose loss in urine signals a fasting state to the liver, which leads to an increased FA oxidation and ketone body production. Disclosure T. Kroon: Employee; Self; AstraZeneca. T. Hagstedt: None. A. Kjellstedt: None. A. Lindblom: Employee; Self; AstraZeneca. L. Löfgren: Employee; Self; AstraZeneca. J. Boucher: Employee; Self; AstraZeneca. M. Sörhede Winzell: Employee; Self; AstraZeneca. D. Linden: Employee; Self; AstraZeneca. K. Wallenius: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca.

Varying Protein Quantity and Quality in the Maternal Diet During the Perinatal Period Affects Growth and Adiposity Risk in Female Adult Offspring in Rats (OR09-03-19)

ObjectivesMaternal diet in the perinatal period can program health of adult offspring. This study evaluates the consequences of maternal dietary protein quality and quantity during gestation and lactation on overweight risk in female offspring subjected to dietary self-selection (DSS). MethodsSix groups of rat dams were fed a high-protein (HP; 47% protein) or normal protein (NP; 19% protein) isocaloric diet during gestation. Protein sources of HP and NP diets were either milk (M), pea (P), or turkey (T)-derived. During lactation, dams were fed NP diet containing the protein source as fed during pregnancy. From postnatal day (PND) 28 to 70, pups (n = 8 per group) were exposed to DSS with a choice between five cups containing either: HP-M, HP-P, HP-T diets, or only carbohydrates or only lipids. Pups’ weight gain and food intake were recorded daily. Body composition, fasting plasma insulin and leptin levels were assessed at the end of the study (PND70). ResultsDuring lactation, pups’ weight gain was lower in the “turkey and pea” compared to “milk” group (P < 0.0001), resulting in a lower weight gain in the “pea” compared to “milk” group at the end of the lactation period (PND28; P < 0.0001). Body weight gain from PND28 to 70 was also lower in the “pea and turkey “compared to “milk” group (P < 0.0001). Total food intake throughout the postweaning period, was lower in the “pea and turkey” compared to “milk” group (P < 0.05). At PND70, body composition was affected by (i) the maternal protein source showing a lower adipose tissue weight in the “pea and turkey” compared to “milk” group (P = 0.01), but also by (ii) the maternal protein quantity showing increased adipose tissue weight (≥16%) in HP compared to NP gestation groups (P = 0.03) (figure 1), regardless of the protein source in the maternal diet. In accordance with the increased adipose tissue weight in HP groups, fasting plasma leptin levels were significantly higher in HP compared to NP gestation groups (P < 0.05). Plasma insulin levels were not affected. ConclusionsDietary protein source during gestation and lactation directly affected weight gain of the offspring after weaning and at adulthood. HP diet during gestation resulted in a higher adiposity in the offspring, independent of the protein source. Funding SourcesThis thesis work was partly funded by Danone Nutricia Research. Supporting Tables, Images and/or Graphs▪

1860-P: Liver Fat and Visceral Fat Are Associated with Different Metabolic and Pathophysiologic Profiles but with Similar Relationships with Whole Body Insulin Resistance

MRI-based examinations of hepatic steatosis and body fat are becoming more familiar and useful for metabolic studies including NAFLD. MRI-estimated proton density fat fraction (MRI-PDFF) can haptic fat exactly without biopsy, enabling us to evaluate the effect of liver fat more sophisticatedly than ever. Although hepatic fat and visceral fats are both important for metabolic and cardiovascular diseases, detailed evaluation of the effect of each fat depot on various metabolic profiles have not been performed, In the present study, we evaluated the differential effect between hepatic and visceral fats on various metabolic profiles including glucose and lipid metabolism, islet cell function, insulin resistance, and inflammation. A total of 82 subjects (25 healthy volunteers and 57 patients with suspected, or proven NAFLD) who underwent MRI examinations for MRI-PDFF and visceral fat measurement. Additionally, anthropometric and laboratory studies and total body fat measurement by DXA were also performed. Other causes of chronic liver diseases, such as alcoholic, autoimmune or viral hepatitis, and other diseases, were excluded from the study. The amounts of hepatic fat and visceral fats measured by MRI showed similar significant correlations with HOMA-IR (r=0.540 vs. r=0.538, p &amp;lt;0.01, respectively) as with A1C (r=0.448 vs. r=0.495, p &amp;lt;0.01 each). However, hepatic fat showed more close association with FBS, triacylglycerol, complement factor C3, and cytokeratin 18. Visceral fat correlated more with fasting plasma insulin, glucagon and angiotensinogen levels. Total body fat measured by DXA did not show such characteristic patterns of correlations and showed only a weak or no correlation with those parameters. Thus, our results showed that both hepatic fat and visceral fat depots are important determinants of whole-body insulin resistance and glucose metabolism. Disclosure I. Park: None. K. Lee: None. D. Lee: None.

2011-P: Totum-63 Lowers Adipose Tissue Inflammation and Reverses Both Hepatic Steatosis and Insulin Resistance in High-Fat Diet-Induced Obese Mice

The worldwide prevalence of obesity, metabolic syndrome and type 2 diabetes (T2D) is reaching epidemic proportions that urge the development of new therapeutic strategies. Obesity-associated meta-inflammation contributes to nonalcoholic fatty liver disease (NAFLD) and plays a central role in the development of insulin resistance and T2D. Totum-63 has recently been developed for the management of prediabetes and shown to prevent high-fat diet (HFD)-induced metabolic disorders in mice. In the present study, we investigated whether Totum-63 could also improve metabolic homeostasis in insulin-resistant obese mice. For this purpose, C57Bl6/J male mice were fed a low- (LFD) or HFD for 12 weeks followed by supplementation with or without Totum-63 (2.7% w/w) for 4 additional weeks. Although no metabolic phenotype was observed in LFD-fed mice, Totum-63 decreased body weight in HFD-fed mice, an effect exclusively due to reduced fat mass and associated with a transient reduction in food intake confined to the first days of supplementation. The liver and brown adipose tissue weights were significantly reduced, whereas adipose tissue (AT) mass and adipocyte size distribution were not affected. Totum-63 markedly reduced hepatic macrovesicular steatosis and liver triglyceride content. Furthermore, potent decreases in fasting plasma glucose, insulin and leptin levels, and improvements in systemic insulin sensitivity and glucose tolerance were observed. Remarkably, a significant reduction in AT M1-like pro-inflammatory macrophages was found, indicating that Totum-63 can modulate macrophage recruitment/polarization and lower HFD-induced AT inflammation. Altogether, our results strongly suggest that Totum-63 reverses hepatic steatosis and insulin resistance in obese mice at least partly by dampening meta-inflammation, constituting a promising new approach for alleviating NAFLD and metabolic dysfunctions in established T2D. Disclosure H.J. van der Zande: None. A. Zawistowska-Deniziak: None. F. Otto: None. V. Chavanelle: Employee; Self; Valbiotis. S. Peltier: Board Member; Self; Valbiotis. P. Sirvent: Board Member; Self; Valbiotis. B. Guigas: Advisory Panel; Self; Valbiotis. Research Support; Self; Valbiotis.

Silencing of SAA1 inhibits palmitate- or high-fat diet induced insulin resistance through suppression of the NF-\u03baB pathway

BackgroundObesity is one of the leading causes of insulin resistance. Accumulating reports have highlighted that serum amyloid A-1 (SAA1) is a potential candidate that is capable of attenuating insulin resistance. Hence, we conducted the current study with aims of investigating our proposed hypothesis that silencing SAA1 could inhibit the progression of obesity-induced insulin resistance through the NF-κB pathway.MethodsGene expression microarray analysis was initially performed to screen differentially expressed genes (DEGs) associated with obesity. Palmitate (PA)-induced insulin resistance Huh7 cell models and high-fat diet (HFD)-induced mouse models were established to elucidate the effect of SAA1/Saa1 on insulin resistance. The NF-κB pathway-related expression was subsequently determined through the application of reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis.ResultsSaa1 was identified as an obesity-related gene based on the microarray data of GSE39549. Saa1 was determined to be highly expressed in HFD-induced insulin resistance mouse models. PA-induced Huh7 cells, treated with silenced SAA1 or NF-κB pathway inhibition using BAY 11–7082, displayed a marked decrease in both Saa1 and SOCS3 as well as an elevation in 2DG, IRS1 and the extent of IRS1 phosphorylation. HFD mice treated with silenced Saa1 or inhibited NF-κB pathway exhibited improved fasting blood glucose (FBG) levels as well as fasting plasma insulin (FPI) levels, glucose tolerance and systemic insulin sensitivity. Saa1/SAA1 was determined to show a stimulatory effect on the transport of the NF-κBp65 protein from the cytoplasm to the nucleus both in vivo and in vitro, suggesting that Saa1/SAA1 could activate the NF-κB pathway.ConclusionTaken together, our key findings highlight a novel mechanism by which silencing of SAA1 hinders PA or HFD-induced insulin resistance through inhibition of the NF-κB pathway.

Baseline fasting plasma insulin levels predict risk for major adverse cardiovascular events among patients with diabetes and high-risk vascular disease: Insights from the ACCELERATE trial.

Despite optimal treatment, type II diabetes mellitus remains associated with an increased risk for future cardiovascular events. We sought to determine the association between baseline fasting plasma insulin levels and major adverse cardiovascular outcomes in patients with type II diabetes mellitus and high-risk vascular disease enrolled in the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial. We included all patients with type II diabetes mellitus who had a central laboratory measured fasting plasma insulin level drawn at baseline as part of the study protocol. Hazard ratios were generated for the risk of major adverse cardiovascular outcomes (composite of cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina and coronary revascularization) with increasing quartile of baseline fasting plasma insulin level. We then performed a multivariable regression adjusting for significant baseline characteristics. Among 12,092 patients in ACCELERATE, 2042 patients with type II diabetes mellitus had a baseline fasting plasma insulin level drawn. Median follow-up was 28 months. The study population had a mean age of 66.6 years, 79.2% male and 96.2% had established coronary artery disease. During follow-up, major adverse cardiovascular outcomes occurred in 238 patients (11.6%); of these events, 177 were coronary revascularization (8.7%). We observed a statistically significant relationship between rates of revascularization and rising quartile of baseline fasting plasma insulin level which was not noted for the other individual components of major adverse cardiovascular outcomes. Patients with type II diabetes mellitus who underwent revascularization were noted to have significantly higher baseline fasting plasma insulin levels (27.7 vs 21.4 mU/L, p-value = 0.009) although baseline haemoglobin A1c (6.63% vs 6.55%), body mass index (31.5 vs 31.1 kg/m2) and medical therapy were otherwise similar to the group not undergoing revascularization. Following multivariable regression adjusting for significant characteristics including exposure to evacetrapib, the log of baseline fasting plasma insulin level was found to be an independent predictor for major adverse cardiovascular outcomes (hazard ratio = 1.36, 95% confidence interval = 1.09-1.69, p-value = 0.007); this was driven by need for future revascularization (hazard ratio = 1.56, 95% confidence interval = 1.21-2.00, p-value = 0.001). In a contemporary population of patients with type II diabetes mellitus and high-risk vascular disease on optimum medical therapy, baseline hyperinsulinaemia was an independent predictor for major adverse cardiovascular outcomes and need of future coronary revascularization. These results suggest a pathophysiological link between hyperinsulinaemia and progression of atherosclerotic vascular disease among diabetics.

Protocol for a cross sectional study of cancer risk, environmental exposures and lifestyle behaviors in a diverse community sample: the Community of Mine study

BackgroundPhysical inactivity and unhealthy diet are modifiable behaviors that lead to several cancers. Biologically, these behaviors are linked to cancer through obesity-related insulin resistance, inflammation, and oxidative stress. Individual strategies to change physical activity and diet are often short lived with limited effects. Interventions are expected to be more successful when guided by multi-level frameworks that include environmental components for supporting lifestyle changes. Understanding the role of environment in the pathways between behavior and cancer can help identify what environmental conditions are needed for individual behavioral change approaches to be successful, and better recognize how environments may be fueling underlying racial and ethnic cancer disparities.MethodsThis cross-sectional study was designed to select participants (n = 602 adults, 40% Hispanic, in San Diego County) from a range of neighborhoods ensuring environmental variability in walkability and food access. Biomarkers measuring cancer risk were measured with fasting blood draw including insulin resistance (fasting plasma insulin and glucose levels), systemic inflammation (levels of CRP), and oxidative stress measured from urine samples. Objective physical activity, sedentary behavior, and sleep were measured by participants wearing a GT3X+ ActiGraph on the hip and wrist. Objective measures of locations were obtained through participants wearing a Qstarz Global Positioning System (GPS) device on the waist. Dietary measures were based on a 24-h food recall collected on two days (weekday and weekend). Environmental exposure will be calculated using static measures around the home and work, and dynamic measures of mobility derived from GPS traces. Associations of environment with physical activity, obesity, diet, and biomarkers will be measured using generalized estimating equation models.DiscussionOur study is the largest study of objectively measured physical activity, dietary behaviors, environmental context/exposure, and cancer-related biomarkers in a Hispanic population. It is the first to perform high quality measures of physical activity, sedentary behavior, sleep, diet and locations in which these behaviors occur in relation to cancer-associated biomarkers including insulin resistance, inflammation, impaired lipid metabolism, and oxidative stress. Results will add to the evidence-base of how behaviors and the built environment interact to influence biomarkers that increase cancer risk.Trial registrationClinicalTrials.gov NCT02094170, 03/21/2014.

Beta-cell function and insulin resistance among First-Degree relatives of persons with type 2 diabetes in a Northwestern Nigerian Population

Background and Aims: Pancreatic beta-cell deficit and insulin resistance (IR) form two major factors in the etiopathogenesis of type 2 diabetes. The aim of this study is to assess beta-cell function and IR among first-degree relatives (FDRs) of persons with type 2 diabetes in a Northwestern Nigerian population. Other objectives include assessing the relationships among HOMA-%B, HOMA-IR, plasma glucose levels, and some obesity indices and to determine whether beta cell function, IR, and some obesity indices are independent determinants of glucose intolerance in the studied population. Materials and Methods: A total of 200 individuals and 200 controls were recruited through cluster sampling from their respective communities after due consent. The relevant biodata was documented and appropriate examinations including anthropometric measurements were carried out. Oral glucose tolerance test was carried out and fasting plasma insulin levels were also measured. IR and beta-cell function were calculated using homeostasis model assessment (HOMA) method. Results: Mean HOMA-IR was higher while HOMA-% B lower among FDRs compared to controls. Significant independent determinants of glucose intolerance with odds ratio (OR) and confidence interval (CI) included age (OR = 1.9, CI 1.9–2.0, P = 0.002), body mass index (OR = 1.9, CI 1.8–2.0, P = 0.032), waist circumference (OR = 2.0, CI 1.9–2.0, P = 0.043), waist-to-hip ratio (OR = 1.1, CI 1.0–15.7, P = 0.022), HOMA-IR (OR = 3.0, CI 2.3–3.3, P

Oral Ang-(1-7) treatment improves white adipose tissue remodeling and hypertension in rats with metabolic syndrome

ObjectiveAngiotensin (Ang)-(1-7) has preventive effects on metabolic syndrome (MetS). The aim of this study was to evaluate the therapeutic effect of oral Ang-(1-7) on mean arterial pressure (MAP), insulin resistance (IR), inflammatory process, and remodeling of white adipose tissue (WAT) in rats with established MetS. MethodsRats were subjected to control (CT; AIN-93M) or high-fat (HF) diets for 13 wk to induce MetS and treated with Ang-(1-7) or vehicle (V) for the last 6 wk. At the end of 13 wk, MAP, biochemical and histological parameters, and uncoupling protein (UCP) and inflammatory gene expression were determined by quantitative reverse transcription polymerase chain reaction. ResultsHF-V rats showed increased visceral fat deposition, inflammatory cytokine expression, hyperplasia, and hypertrophy in retroperitoneal (WAT) and brown adipose tissue (BAT). Additionally, the gastrocnemius muscle reduced UCP-3 and increased the UCP-1 expression in BAT. HF-V also elevated levels of plasma insulin, glucose, homeostatic model assessment (HOMA) of IR and HOMA-β, and increased body mass, adiposity, and MAP. Ang-(1-7) treatment in rats with MetS [HF-Ang-(1-7)] reduced WAT area, number of adipocytes, and expression of proinflammatory adipokines in WAT and BAT and increased UCP-3 in gastrocnemius muscle and UCP-1 expression in BAT compared with the HF-V group. These events prevented body mass gain, reduced adiposity, and normalized fasting plasma glucose, insulin levels, HOMA-IR, HOMA-β, and MAP. ConclusionData from the present study demonstrated that oral Ang-(1-7) treatment is effective in restoring biochemical parameters and hypertension in established MetS by improving hypertrophy and hyperplasia in WAT and inflammation in adipose tissue, and regulating metabolic processes in the gastrocnemius muscle and BAT.

Study of carbohydrate metabolism indicators in firstly diagnosed pulmonary tuberculosis patients

Objective — to study the indicators of carbohydrate metabolism in patients with firstly diagnosed pulmonary tuberculosis, depending on the extent of the lesion and the presence of mycobacteria excretion.Materials and methods. 78 patients with firstly diagnosed pulmonary tuberculosis were examined, including 19 patients without mycobacteria excretion — Group 1 and 59 patients with mycobacteria excretion — Group 2. The control group — 20 healthy individuals, comparable by sex and age. The examination and diagnosis were carried out in accordance with the current order of the Ministry of Health of Ukraine. Additionally, patients underwent oral glucose tolerance test (OGTT), the fasting insulin level was determined, the insulin resistance index (HOMA-IR) and the body mass index were calculated. For statistical data processing, the general-purpose data processing software package Statistica for Windows version 13.2 was used.Results and discussion. Depending on the increase in the volume of lung lesions, a monotonic increase of the level of glycated hemoglobin was observed from 4.8 % (pathological changes within the lung lobe) to 6 % (total lesion of the lung) with a maximum value of 7.1 % in bilateral lung lesions. The results of the oral glucose tolerance test demonstrated a statistically significant increase of the indicator to a median level of 5.8 mmol/l in the group of patients with mycobacteria excretion compared to 4.7 mmol/l in the group without mycobacteria excretion. In patients with firstly diagnosed pulmonary tuberculosis, the fasting plasma insulin level on an empty stomach exceeded 3.8 times compared to the control group, and the HOMA-IR insulin resistance index almost 4 times, indicating an increased insulin secretion by pancreatic β-cells.Conclusions. An increased 2 hours blood glucose level, fasting insulin level, and the HOMA-IR index was typical for firstly diagnosed pulmonary tuberculosis patients, which indicates the development of insulin resistance, a pathological condition characterized by an insufficient biological response of the cell to insulin at its sufficient concentration in the blood. Compared with patients who had limited pathological changes, patients with bilateral lesions of the lungs were characterized by a more prolonged violation of carbohydrate metabolism, as indicated by the levels of glycosylated hemoglobin upon admission to the hospitalMycobacteria excretion, as a marker of an aggravated course of the disease, was accompanied by the appearance of latent carbohydrate metabolism disorders in the form of an increase of 2 hours blood glucose level, that is, an impaired glucose tolerance.

The Effects of Synbiotic Supplementation on Metabolic Status in Diabetic Patients Undergoing Hemodialysis: a Randomized, Double-Blinded, Placebo-Controlled Trial.

This study was conducted to evaluate the effects of synbiotic supplementation on metabolic profiles in diabetic patients undergoing hemodialysis (HD). This randomized, double-blinded, placebo-controlled clinical trial was performed in 60 diabetic HD patients. Participants were randomly assigned into two groups to receive either synbiotic capsule, containing Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum (2 × 109CFU/g each), plus 0.8g/day of inulin (n = 30) or placebo (n = 30) for 12weeks. Synbiotic supplementation significantly decreased fasting plasma glucose (β - 13.56mg/dL; 95% CI, - 23.82, - 3.30; P = 0.01), insulin levels (β - 5.49μIU/mL; 95% CI, - 6.92, - 4.05; P < 0.001), and insulin resistance (β - 2.25; 95% CI, - 3.02, - 1.48; P < 0.001), while increased the quantitative insulin sensitivity check index (β 0.02; 95% CI, 0.01, 0.02; P < 0.001) compared with the placebo. Additionally, synbiotic intake resulted in a significant reduction in high-sensitivity C-reactive protein (β - 2930.48ng/mL; 95% CI, - 3741.15, - 2119.80; P < 0.001) and malondialdehyde levels (β - 0.60μmol/L; 95% CI, - 0.99, - 0.20; P = 0.003). Moreover, we found a significant increase in total antioxidant capacity (β 142.99mmol/L; 95% CI, 61.72, 224.25; P = 0.001) and total glutathione levels (β 131.11μmol/L; 95% CI, 89.35, 172.87; P < 0.001) in the synbiotic group compared with the placebo group. Overall, synbiotic supplementation for 12weeks had beneficial effects on glycemic control, biomarkers of inflammation, and oxidative stress in diabetic patients under HD. This study was registered in the Iranian website (www.irct.ir) for registration of clinical trials (http://www.irct.ir: IRCT2017090133941N17). http://www.irct.ir: IRCT2017090133941N17.

Protein malnutrition mitigates the effects of a high-fat diet on glucose homeostasis in mice.

Nutrient malnutrition, during the early stages of development, may facilitate the onset of metabolic diseases later in life. However, the consequences of nutritional insults, such as a high-fat diet(HFD) after protein restriction, are still controversial. We assessed overall glucose homeostasis and molecular markers of mitochondrial function in the gastrocnemius muscle of protein-restricted mice fed an HFD until early adulthood. Male C57BL/6 mice were fed a control (14% protein-control diet) or a protein-restricted (6% protein-restricted diet) diet for 6 weeks. Afterward, mice received an HFD or not for 8 weeks (mice fed a control diet and HFD [CH] and mice fed a protein-restricted diet and HFD [RH]). RH mice showed lower weight gain and fat accumulation and did not show an increase in fasting plasma glucose and insulin levels compared with CH mice. RH mice showed higher energy expenditure, increased citrate synthase, peroxisome-proliferator-activated receptor gamma coactivator 1-alpha protein content, and higher levels of malate and α-ketoglutarate compared with CH mice. Moreover, RH mice showed increased AMPc-dependent kinase and acetyl coenzyme-A (CoA) carboxylase phosphorylation, lower intramuscular triacylglycerol content, and similar malonyl-CoA levels. In conclusion, protein undernourishment after weaning does not potentiate fat accumulation and insulin resistance in adult young mice fed an HFD. This outcome seems to be associated with increased skeletal muscle mitochondrial oxidative capacity and reduced lipids accumulation.

Ghrelin Levels in Basal Conditions and During Glucose Tolerance Test in Prediabetic and Diabetic Patients.

Ghrelin is associated with glucose homeostasis but its' possible relevance with glucose levels in physiological and pathological conditions has so far been poorly investigated. The aim of the present study was to evaluate circulating ghrelin levels in prediabetic and diabetic patients in basal conditions and in response to oral glucose tolerance test (OGTT). A total of 90 male adults aged 40 - 73 years old were enrolled in our study. Fasting and postprandial plasma ghrelin, insulin and glucose levels were measured at 0, 60, 120 and 180 min following an OGTT in 40 patients with type 2 diabetes mellitus (T2DM), 20 with impaired glucose tolerance (IGT) and 30 controls. Incremental and total area under response curve were determined and calculated for glucose, insulin and ghrelin. Fasting plasma ghrelin concentrations were significantly lower in the T2DM group than IGT and control group patients (p<0.01) but not between healthy subjects and IGT group (p=0.746). In the diabetics' group ghrelin levels showed a statistically significant negative correlation with insulin and a positive correlation with HbA1c and glucose. At all time points after the OGTT ghrelin concentrations were significantly lower in the T2DM group compared to IGT group and controls. Plasma ghrelin concentrations are lower in male diabetic patients at the fasting state and remain lower at all time points after an OGTT while minor differences were found between normal and IGT subjects. Ghrelin might play a role in insulin and glucose metabolism in diabetic patients but not in patients with IGT.

Effect of duration of diabetes on bone mineral density: a population study on East Asian males

BackgroundThe aim of the present study is to evaluate the association between BMD and type 2 DM status in middle-aged and elderly men. To investigate a possible correlation, the present study used the BMD dataset of the Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2011.MethodsIn total, 37,753 individuals participated in health examination surveys between 2008 and 2011. A total of 3383 males aged ≥50 years were eligible. They underwent BMD measurement through dual-energy X-ray absorptiometry (DXA). The fasting plasma glucose and insulin levels of participants were also measured.ResultsMen with prediabetes and diabetes had significantly higher mean BMD at all measured sites than control men did, irrespective of DM status. This was confirmed by multivariable linear regression analyses. DM duration was an important factor affecting BMD. Patients with DM for > 5 years had lower mean BMD in the total hip and femoral neck than those with DM for ≤5 years. Per multivariable linear regression analyses, patients with DM for > 5 years had significantly lower mean BMD at the femoral neck than those with DM ≤5 years.ConclusionsDM duration was significantly associated with reduced femoral neck BMD.

Efficacy of different antidiabetic drugs based on metformin in the treatment of type 2 diabetes mellitus: A network meta-analysis involving eight eligible randomized-controlled trials.

Diabetes mellitus is one of the most prevalent metabolic diseases globally and it is increasing in prevalence. It is one of the most expensive diseases with respect to total health care costs per patient as a result of its chronic nature and its severe complications. To provide a more effective treatment of type 2 diabetes mellitus (T2DM), this study aims to compare different efficacies of six kinds of hypoglycemic drugs based on metformin, including glimepiride, pioglitazone, exenatide, glibenclamide, rosiglitazone, and vildagliptin, in T2DM by a network meta-analysis that were verified by randomized-controlled trials (RCTs). Eight eligible RCT in consistency withthe aforementioned six hypoglycemic drugs for T2DM were included. The results of network meta-analysis demonstrated that the exenatide + metformin and vildagliptin + metformin regimens presented with better efficacy. Patients with T2DM with unsatisfactory blood glucose control based on diet control, proper exercise, and metformin treatment were included. The original regimen and dose of medication were unchanged, followed by the addition of glimepiride, pioglitazone, exenatide, glibenclamide, rosiglitazone, and vildagliptin. The results of RCTs showed that all these six kinds of drugs reduced the HbA1c level. Compared with other regimens, exenatide + metformin reduced fasting plasma glucose (FPG), fasting plasma insulin (FPI), total cholesterol (TC), and homeostasis model assessment insulin resistance index (HOMA-IR) levels, but increased the high-density lipoprotein (HDL) level; vildagliptin + metformin decreased FPI and low-density lipoprotein (LDL) levels; glibenclamide + metformin decreased the FPG level, butpromoted HDL; and glimepiride + metformin decreased the TC level and rosiglitazone + metformin reduced the LDL level. Our findings indicated that exenatide + metformin and vildagliptin + metformin have better efficacy in T2DM since they can improve insulin sensitivity.

An assessment of the relationship between thyroid nodule characteristics, insulin resistance and arterial stiffness in euthyroid nodular goiter.

Publications suggesting that thyroid nodule might be associated with insulin resistance and metabolic syndrome are quite interesting. There is a need for studies assessing the relationship between nodule presence and cardiovascular risk in individuals with non-functioning nodular goiter. The purpose of the present study is to reveal whether or not insulin resistance, nodule presence, and nodule stiffness affect arterial stiffness, which is a reliable and valid cardiovascular risk indicator, in individuals with euthyroid nodular goiter using the pulse wave analysis (PWA). 50 patients with euthyroid nodular goiter and 50 healthy volunteers were included in the study. All participants were examined by B-mode thyroid ultrasound, and the participants in the nodular goiter group were also examined by strain elastography (SE). The strain index of nodules was calculated according to the Rago scoring. Also, fasting plasma glucose (FPG) and insulin levels were measured, and HOMA-IR. Arterial stiffness measurements of the participants were performed using a PWA device which employs a cuff-based oscillometric method from the brachial artery. PWV was found to be significantly higher in the euthyroid nodular goiter group (p < 0.001). PWV was found to be positively correlated with FPG and waist circumference. Fasting plasma glucose was found to be higher in the group with nodular goiter (p = 0.03). However, no difference was found between the groups in terms of HOMA-IR and insulin level. HOMA-IR was not correlated with thyroid volume, nodule volume, and nodule count. Also, HOMA-IR was not correlated with strain index value and PWA data. We found that PWV was significantly higher in patients with euthyroid nodular goiter. This result suggests that these patients may be at risk for cardiovascular disease.

Submucosal fat accumulation in human colorectal tissue and its association with abdominal obesity and insulin resistance

In addition to visceral fat, peripheral ectopic fat accumulation is suggested to play a role in the pathophysiology of metabolic syndrome, which is known to be associated with not only cardiovascular diseases and type 2 diabetes mellitus but also colorectal cancer. This study aims to clarify whether there is ectopic fat accumulation in human colorectal tissue in association with metabolic syndrome or its components such as abdominal obesity and insulin resistance. Lipid contents of colorectal tissue were measured in 27 patients with colorectal polyp excised endoscopically. In addition, lipid droplets were immunohistochemically estimated using anti-perilipin antibody in 32 patients with colorectal cancer resected surgically. Increasing tissue triglyceride/phospholipid ratio was associated with increasing body mass index, fasting plasma insulin level and homeostasis model assessment as an index of insulin resistance (HOMA-IR), and also decreasing serum adiponectin level. Lipid droplets were observed in the submucosal region of colorectal tissue. The amount of lipid droplets was associated with increasing body mass index, waist circumference and visceral fat area. This study showed the presence of submucosal fat accumulation in human colorectal tissue and its association with abdominal obesity and insulin resistance.

EVALUATION OF THE OF INSULIN RESISTANCE EFFECTS ON OBESITY AND RELATED PARAMETERS

Obesity, especially abdominal obesity, is one of the most important underlying risk factors for metabolic syndrome and increases the risk of developing various pathological conditions like Type 2 Diabetes Mellitus, dyslipidemia, hypertension and Non Alcoholic Fatty Liver Disease. Insulin resistance means that the ability of insulin to stimulate glucose utilization is reduced, it is an integral feature of the metabolic syndrome and an important predictor of Type 2 Diabetes Mellitus development. It is well known that obesity is associated with diabetes mellitus, and the main basis of this link is thought to be the ability of obesity to stimulate insulin resistance. In this study, we aimed to evaluate the relationship between insulin resistance and obesity, related biochemical parameters, body analysis data. In this retrospective case control study, the insulin resistance status of 120 volunteers in Samsun Buyuk Anadolu Hospital's Nutrition and Diet Policlinic was determined by calculating the Homeostatic Model Assessment-Insulin Resistance formula. Biochemical values and body analysis results of individuals with and without insulin resistance were compared. Insulin resistance was detected in 56 (%46,7) of the subjects participating in the study. Insulin resistance was significantly related with weight, body mass index, body fat mass, abdominal fat mass (p 0,05). Fasting plasma glucose, HbA1c percentages, insulin, triglyceride and ALT levels were found to be higher in individuals with insulin resistance (p 0,05). In conclusion, considering the risks of diseases caused by insulin resistance, findings of this study emphasizes the importance of detecting insulin resistance. Determining the presence of insulin resistance can help prevent a variety of diseases by regulating nutrition. Detection of insulin resistance and regulation of nutrition can help prevent various diseases.

Immobilization in diabetic rats results in altered glucose tolerance A model of reduced locomotion/activity in diabetes

AbstractAims Type 2 Diabetes Mellitus affects more than 350 million people worldwide. This metabolic disorder is characterized by insulin resistance, β‐cell dysfunction and elevated hepatic glucose output. Patients with diabetes are hospitalized frequently (3‐fold greater) and with longer admissions (30% longer) than the non‐diabetic subjects. The aim of the present study was to investigate the impact of bed rest on the metabolic changes in type 2 diabetes mellitus, with particular interest in skeletal muscle mass and function and metabolism.Methods and results 13wk old male Zucker diabetic fatty (ZDF) rats were randomly divided into two groups: control (ZDF‐Con) and cage‐immobilized animals (ZDF‐Cage) for 28 consecutive days in a space‐restricted cage. The Area Under the Curve (AUC) values for plasma glucose concentration in ZDF‐Cage rats were significantly increased (approximately 4‐fold as compared with ZDF‐Con rats). GLUT4 gene expression in red soleus muscle of ZDF‐Cage animals was reduced 2.5‐fold in comparison with ZDF‐Con rats. Although no apparent changes were observed either in fasting plasma glucose or insulin levels, a trend towards an increase in the HOMA‐IR index and decreased levels of plasma adiponectin (‐30%) were observed in ZDF‐Cage animals. Moreover, ZDF‐Cage rats did not lose muscle mass and force but performed a reduced total physical activity level (‐22%).Conclusions The present study results suggests that 28 days of immobilization (in a space‐restriction model) significantly impaired glucose tolerance with concomitant reduced plasmatic adiponectin levels and GLUT4 expression in soleus muscle of type 2 diabetic rats.