Increased Fasting Glucose Levels Research Articles

Gestational diabetes mellitus is associated with distinct folate-related metabolites in early and mid-pregnancy: A prospective cohort study.

This study aimed to evaluate the association between gestational diabetes mellitus (GDM) and circulating folate metabolites, folic acid (FA) intake, and the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genotype. A prospective pregnancy cohort study was conducted in Beijing, China, from 2022 to 2023. Circulating folate metabolites, including red blood cell (RBC) 5-methyltetrahydrofolate (5-MTHF), 5, 10-methylene-tetrahydrofolate (5,10-CH2-THF), 5- formyltetrahydrofolate (5-CHO-THF), and unmetabolised folic acid (UMFA), and plasma homocysteine (HCY), 5-MTHF, and methylmalonic acid (MMA), were determined at 6-17weeks and 20-26weeks of gestation. FA intake and the MTHFR and MTRR genotype were also examined. GDM was diagnosed between 24 and 28weeks of pregnancy by a 75-g oral glucose tolerance test (OGTT). The association between the folate status and GDM was ascertained using multivariate generalised linear models, logistic regression models, and restricted cubic spline regression, adjusting for potential confounders. The study included 2032 pregnant women, of whom 392 (19.29%) developed GDM. UMFA above the 75th percentile (≥P75) [adjusted OR (aOR) (95% confidence interval [CI])=1.36 (1.01-1.84)], UMFA≥P90 [aOR (95% CI)=1.82 (1.23-2.69)], and HCY≥P75 [aOR (95% CI)=1.40 (1.04-1.88)] in early pregnancy, and RBC 5-MTHF [aOR (95% CI)=1.48 (1.10-2.00)], RBC 5,10-CH2-THF [aOR (95% CI)=1.55 (1.15-2.10)], and plasma 5-MTHF [aOR (95% CI)=1.36 (1.00-1.86)] in mid-pregnancy≥P75 are associated with GDM. Higher UMFA levels in early pregnancy show positive associations with the 1-h and 2-h glucose levels during the OGTT, and higher HCY levels are associated with increased fasting glucose levels during the OGTT. In comparison, RBC 5- MTHF and 5,10-CH2-THF, and plasma 5- MTHF in mid-pregnancy are positively associated with the 1-h glucose level (p<0.05). The MTHFR and MTRR genotype and FA intake are not associated with GDM. Elevated levels of UMFA and HCY during early pregnancy, along with elevated RBC 5-MTHF and 5,10-CH2-THF and plasma 5-MTHF during mid-pregnancy, are associated with GDM. These findings indicate distinct connections between different folate metabolites and the occurrence of GDM.

Нарушения углеводного обмена у пациентов с боевыми травмами

Aim. To investigate the prevalence and some aspects of the carbohydrate metabolism pathology in patients with combat limb injuries. Materials and methods. 210 patients who suffered from combat injuries of the lower and/or upper extremities from 4 to 58 days (mean 15.9±8.7 days) before admission to the hospital were enrolled in the study. All study participants were men. The mean age of the patients was 36.0±8.4 years (19–59 years). Fasting venous blood glucose concentrations were determined in all patients. Patients with hyperglycemia underwent a study of the glycemic profile and HbA1c. Stress-induced hyperglycemia, estimated mean glucose level over the past 3 months (ADAG), and glycemic gap were calculated. Insulin in fasting blood plasma was determined and the HOMA-IR insulin resistance index was calculated. Results. The incidence of hyperglycemia was 23.3%. In the general group of patients, the mean glucose concentration was 5.5±1.0 mmol/l (3.1–9.73 mmol/l). In the group of patients with hyperglycemia, the mean blood glucose level reached 6.7±0.9 mmol/l, in patients with normal glucose concentration – 5.1±0.5 mmol/l (p&lt;0.000001). The mean fasting blood glucose concentration in patients aged 40 years and older reached 5.7±1.1 mmol/l, those under 40 years old – 5.2±0.8 mmol/l (p=0.005). A significant direct correlation was registered between the fasting glucose level upon admission to the hospital and the age of the patients (r=0.26; p=0.00003). The relative risk of hyperglycemia in patients aged 40 years and older was 1.84 (confidence interval 1.005–3.37; p=0.01). The mean time elapsed since injury in patients with hyperglycemia reached 13.2±5.7 days, with normal glucose concentration – 16.7±9.2 days (p=0.02). Patients with hyperglycemia had lower levels of total protein (58.3±10.2 and 62.1±6.9 g/l, respectively; p=0.004), albumin (31.2±4.6 and 33.2±4.9 g/l; p=0.04), hemoglobin (97.7±18.9 and 105.9±16.9 g/l; p=0.004), but higher levels of C-reactive protein (61.0±55.4 and 32.9±38.1 mg/l; p=0.0001), leukocytes (10.6±4.4 and 9.3±3.4×109/l; p=0.02), count of neutrophils (7.8±4.3 and 6.4±2.9×109/l; p=0.01), proportion of neutrophils (71.6±9.6% and 67.7±7.7%; p=0.004), as well as fibrinogen concentration (5.7±1.4 and 4.8±1.2 g/l; p=0.0002) than patients with normal blood glucose levels. In patients with hyperglycemia, the mean HbA1c level was 5.3±0.6%, stress-induced hyperglycemia – 1.4±0.2 mmol/l. The median glycemic gap reached 1.51 mmol/l (Q1–Q3: 0.88–2.1 mmol/l). The median insulin concentration was 12.9 µIU/ml (Q1–Q3: 9.2–27.0 µIU/ml), the insulin resistance index was 3.3 (Q1–Q3: 2.1–8.8). The mean fasting blood glucose concentration at the last determination in patients with initial hyperglycemia reached 5.8±1.3 mmol/l. During observation, in 64.6% of the patients with hyperglycemia upon admission, glucose levels returned to normal, while in 35.4% mild hyperglycemia remained. The median time to normalization of fasting blood glucose concentration or to the last determination of this indicator was 17.5 days (Q1–Q3: 8–30 days). Conclusions. The study results indicate a frequent detection of hyperglycemia in patients with combat limb injuries. In most cases the increase in fasting glucose levels is small and in most patients this indicator returns to normal within a relatively short time. It is necessary to continue research of stress-induced hyperglycemia in the patients with combat injuries and to elucidate the pathogenetic basis of this pathology.

Isoleucine‐restricted diets improve high‐fat diet‐induced nonalcoholic fatty liver disease via regulating insulin resistance and gut microbiota

AbstractObesity, caused by a long‐term high‐fat diet, is a risk factor for insulin resistance and nonalcoholic fatty liver disease (NAFLD). The gut microbiota plays an important role in NAFLD development by producing lipopolysaccharides (LPS). Isoleucine (ILE), as one of the branched‐chain amino acids (BCAAs), has a negative effect on glucose and lipid metabolism in obese mice. Therefore, we speculated that isoleucine‐restricted diets could prevent high‐fat diet‐induced insulin resistance and NAFLD. For this purpose, 30 C57BL/6J mice received a control check diet (CK), a high‐fat diet (HFD), and a isoleucine‐restricted diet (IR) for 12 weeks, respectively. The current study revealed that IR diets reversed HFD‐induced weight gain, increased fasting glucose levels, and lipid metabolism disorder. Furthermore, IR diets attenuated HFD‐induced hepatic inflammation by regulating the LPS/TLR4/NF‐κB signaling pathway. Moreover, hepatic insulin resistance and gluconeogenesis disorder were significantly improved by IR diets. In addition, IR diets reshaped HFD‐induced gut microbiota imbalance, reflected in decreasing the proportion of Proteobacteria phylum and LPS contents. Taken together, our studies support that restricting isoleucine in high‐fat diets was a novel means of preventing obesity‐induced NAFLD and insulin resistance.

Foodborne Carbon Dots Aggravate High-Fat-Diet-Induced Glucose Homeostasis Imbalance by Disrupting the Gut-Liver Axis.

Foodborne carbon dots (CDs) are generally produced during cooking and exist in food items. Generally, CDs are regarded as nontoxic materials, but several studies have gradually confirmed the cytotoxicity of CDs, such as oxidative stress, reduced cellular activity, apoptosis, etc. However, studies focusing on the health effects of long-term intake of food-borne CDs are scarce, especially in populations susceptible to metabolic disease. In this study, we reported that CDs in self-brewing beer had no effect on glucose metabolism in CHOW-fed mice but exacerbated high-fat-diet (HFD)-induced glucose metabolism disorders via the gut-liver axis. Chronic exposure to foodborne CDs increased fasting glucose levels and exacerbated liver and intestinal barrier damage in HFD-fed mice. The 16s rRNA sequencing analysis revealed that CDs significantly altered the gut microbiota composition and promoted lipopolysaccharide (LPS) synthesis-related KEGG pathways (superpathway of (Kdo)2-lipid A, Kdo transfer to lipid IVA Ill (Chlamydia), lipid IVA biosynthesis, and so on) in HFD-fed mice. Mechanically, CD exposure increased the abundance of Gram-negative bacteria (Proteobacteria and Desulfovibrionaceae), thus producing excessive endotoxin-LPS, and then LPS was transferred by the blood circulation to the liver due to the damaged intestinal barrier. In the liver, LPS promoted TLR4/NF-κB/P38 MAPK signaling, thus enhancing systemic inflammation and exacerbating HFD-induced insulin resistance. However, pretreating mice with antibiotics eliminated these effects, indicating a key role for gut microbiota in CDs exacerbating glucose metabolism disorders in HFD-fed mice. The finding herein provides new insight into the potential health risk of foodborne nanoparticles in susceptible populations by disturbing the gut-liver axis.

Anthropometry and blood biomarkers of diabetes and their possible association with obesity and metabolic syndrome.

Diabetes, a rapidly increasing heterogeneous disorder, is closely linked to the epidemic of obesity and metabolic syndrome (MetS). At present, we do not understand completely the blood biomarkers, molecular aetiology, and role of lifestyle modification and interventions to combat diabetes hand in hand with obesity and the MetS epidemic. To measure different anthropometric and blood biomarkers in pre-diabetic and diabetic patients, we collected data and blood samples from patients in a hospital OPD. This was a cross-sectional study that included the identification of possible relationships between different parameters to predict early diagnostic markers of diabetes. We found increased body mass index (BMI), fasting blood glucose, neck, waist, and hip circumference, sagittal abdominal diameter, and skin fold thickness in the diabetic as compared to the pre-diabetic group. Also, serum uric acid and insulin resistance (HOMA-IR) values were significantly increased in diabetic individuals. We found a significant positive correlation between serum uric acid and BMI, fasting blood glucose, serum insulin, and HOMA-IR values. Here, we found that pre-diabetic and diabetic patients have increased fasting glucose levels while we did not find any difference in insulin levels. Both pre-diabetic and diabetic patients show high serum uric acid, positively associated with a higher prevalence of diabetes and HOMA-IR. Uric acid may hence be an important parameter for early diagnostics. These findings may be used as a basis for future studies that aim to identify the mechanistic details of the association of uric acid with insulin signaling and hence better understanding of the phenomenon associated with diabetes. The online version contains supplementary material available at 10.1007/s40200-023-01276-4.

Effect of &lt;i&gt;Gymnema sylvestre&lt;/i&gt; Extract on the Regulation of AMPK-GLUT4 Mediated Signaling Pathway on Insulin Resistance in a PCOS Rat Model

This study was intended to assess the effect of Gymnema sylvestre leaf extract on the AMPK-GLUT4 mediated signalling pathway on insulin resistance in polycystic ovarian syndrome-induced rats. For the induction of PCOS in rats, 1 mg/kg of letrozole was given orally for 21 days, after that metformin (300 mg/kg), Gymnema sylvestre leaf extract (200 mg/kg, and 400 mg/kg p. o.) were administered for further 28 days. Letrozole-induced PCOS rats illustrated significant estrus irregularity, and sex hormonal abnormality, and developed insulin resistance as indicated by increased fasting glucose levels, an increased rate of glucose clearance, and also decreases in GLUT4 and AMPK mRNA expression in ovarian cells. Ovarian histology in PCOS rats also showed many follicular cysts, atretic follicles, and the absence of the corpus luteum. These changes were significantly reversed by the treatment of G. sylvestre in a dose-dependent manner. It might be mediated through its insulin resistance modulating property by the activation of AMPK &amp; GLUT4 expression on ovarian endometrial cells.

Therapeutic exploration of polyherbal formulation against letrozole induced PCOS rats: A mechanistic approach

ObjectiveThis study aimed to develop an effective alternative medicine with multi potential herbs against polycystic ovarian syndrome (PCOS) in rats induced by letrozole treatment. Materials and methodPolyherbal syrup was prepared with a combination of S. asoca bark, G. sylvestre leaves, P. daemia aerial parts, C. zeylanium stem bark, C. bonduc seeds, and W. somnifera roots ethanolic extract. In vitro cell viability study, adenosine monophosphate-activated protein kinase (AMPK), and glucose transporter 4 (GLUT4) gene expression assay were carried out on the Chinese Hamster Ovarian (CHO) cell line. For the PCOS induction letrozole (1 mg/kg p. o.) was given for 21 consecutive days. The PCOS induction was confirmed by measuring estrus irregularity, insulin resistance by oral glucose tolerance test (OGTT), and hyperandrogenism by measuring serum total testosterone level 21 days after completion of letrozole treatment. After induction of PCOS, metformin (155 mg/kg p. o.), and polyherbal syrup (100 mg/kg, 200 mg/kg, and 400 mg/kg p. o.) were administered for further 28 days. The treatment efficacy was measured by measuring serum lipid profile, fasting insulin level, sex hormones level, ovarian steroidogenic enzymes, ovarian tissue insulin receptor, AMPK, and GLUT4 protein expression levels, and histomorphological studies. The post-treatment effect was confirmed by reproductive performance studies. ResultsLetrozole-induced PCOS rats showed significant estrus irregularity, abnormal sex hormones levels, and hyperandrogenism indicated by showing increased free androgenic index and decreased sex hormones binding globulin (SHBG) level. The insulin resistance in PCOS rats was indicated by increased fasting glucose levels with impaired glucose clearance in the OGT test. Homeostasis Model Assessment Index of Insulin Resistance (HOMA-IR) increased level, also decreases INSR, GLUT4, and AMPK mRNA expression in ovarian cells confirming the insulin resistance in PCOS rats. Ovarian histology in PCOS rats also showed many follicular cysts, atretic follicles, and the absence of corpus luteum. The administration of polyherbal syrup, in a dose-dependent manner, effectively restored these alterations. The treatment of polyherbal formulation 400 mg/kg possesses highly significant efficacy over the treatment of metformin in PCOS rats. It mainly acts by reducing peripheral and ovarian hyperandrogenism and improves insulin sensitivity via activating the insulin receptor and AMP-activated kinase-mediated transcription and translation of GLUT4 from the cytoplasm to the ovarian membrane improves glucose uptake and promotes the follicular development and ovulation. The higher fertility rate, delivery index, and survival of delivered pups confirm the broader and superior efficacy of PCOS. These beneficial actions are mainly attributable to the formulation's inclusion of the key secondary metabolites flavonoids and phytosterols. In conclusion, the prepared polyherbal syrup was found to be the safest and most effective alternative medicine for both endocrinal and metabolic complications of PCOS women.

BMP-7 Attenuates Sarcopenia and Adverse Muscle Remodeling in Diabetic Mice via Alleviation of Lipids, Inflammation, HMGB1, and Pyroptosis.

Diabetic myopathy involves hyperglycemia, oxidative stress, and inflammation. However, the role of hypercholesterolemia-induced inflammation-mediated pathological mechanisms leading to fibrosis, sarcopenia, deterioration of muscle, and muscle dysfunction in diabetes is not well understood. In this study, we investigated the novel role of bone morphogenetic protein-7 (BMP-7) in ameliorating metabolic alterations, inflammation, pyroptosis, TGF-β/SMAD cell signaling mechanisms, and progression of diabetic myopathy. C57BL/6J mice were treated with saline, streptozotocin (STZ), or STZ+BMP-7. Diabetes was confirmed by increased fasting glucose levels and a glucose tolerance test. Gastrocnemius muscle and blood samples were collected for lipid and tissue analysis using various methods. A significant increase in hyperglycemia resulted in an increase in lipid accumulation, monocyte infiltration, and inflammation, as well as an increase in pyroptotic markers and signaling markers in diabetic muscle myocytes. A structural analysis showed significant muscle loss, and increased muscle deterioration and fibrosis leading to muscle dysfunction. BMP-7 attenuated pathological processes that resulted in significantly improved muscle function. We report, for the first time, that increased hyperlipidemia aggravates inflammation-induced pyroptosis, resulting in significant muscle loss, sarcopenia, and adverse skeletal muscle remodeling in diabetic muscle myopathy. Interventional treatment with BMP-7 attenuates hypercholesterolemia-induced inflammation-mediated sarcopenia and adverse muscle remodeling, suggesting BMP-7 could be a potential treatment option for diabetic muscle myopathy.

Circadian disruption impairs glucose homeostasis in male but not in female mice and is dependent on gonadal sex hormones.

Circadian disruption (CD) is the consequence of a mismatch between endogenous circadian rhythms and behavior, and frequently occurs in shift workers. CD has often been linked to impairment of glucose and lipid homeostasis. It is, however, unknown if these effects are sex dependent. Here, we subjected male and female C57BL/6J mice to 6-h light phase advancements every 3 days to induce CD and assessed glucose and lipid homeostasis. Within this model, we studied the involvement of gonadal sex hormones by injecting mice with gonadotropin-releasing hormone-antagonist degarelix. We demonstrate that CD has sex-specific effects on glucose homeostasis, as CD elevated fasting insulin levels in male mice while increasing fasting glucose levels in female mice, which appeared to be independent of behavior, food intake, and energy expenditure. Absence of gonadal sex hormones lowered plasma insulin levels in male mice subjected to CD while it delayed glucose clearance in female mice subjected to CD. CD elevated plasma triglyceride (TG) levels and delayed plasma clearance of TG-rich lipoproteins in both sexes, coinciding with reduced TG-derived FA uptake by adipose tissues. Absence of gonadal sex hormones did not notably alter the effects of CD on lipid metabolism. We conclude that CD causes sex-dependent effects on glucose metabolism, as aggravated by male gonadal sex hormones and partly rescued by female gonadal sex hormones. Future studies on CD should consider the inclusion of both sexes, which may eventually contribute to personalized advice for shift workers.

Fasting Plasma Glucose and Its Relationship to Anthropometric Phenotype in Women Diagnosed with Gestational Diabetes According to IADPSG Criteria.

Gestational diabetes mellitus (GDM) is characterized by new-onset hyperglycemia in pregnancy. According to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations, GDM may be diagnosed based on repeatedly increased fasting glucose levels in the first trimester, or later, the detection of increased fasting glucose and/or increased glucose levels during a 75 g oral glucose tolerance test (OGTT). The study aimed to assess whether differences may be found between women diagnosed with GDM by fasting glucose or glucose challenge tests in early or late pregnancy. The retrospective observational study enrolled 418 women diagnosed with GDM in accordance with the IADPSG criteria: early pregnancy fasting plasma glucose (FPG) ≥ 5.1 mmol/L; late pregnancy FPG ≥ 5.1 mmol/L (0 min) and/or postprandial plasma glucose (PPG) ≥ 10.0 mmol/L (60 min), PPG ≥ 8.5 mmol/L (120 min) 75 g OGTT. The analyses included anthropometric parameters at the beginning and during pregnancy, laboratory values of glycated hemoglobin, fructosamine, birth weight measures and the presence of neonatal complications. There were significant differences in body weight (78.3 ± 19.1; 74.0 ± 16.7; 67.2 ± 15.7 kg) and body mass index (BMI) (27.9 ± 6.6; 26.4 ± 5.8; 24.4 ± 5.2 kg/m2) in early pregnancy. Differences were also found in gestational weight gain (9.3 ± 6.8 vs. 12.4 ± 6.9 vs. 11.1 ± 4.7 kg) and the need for insulin therapy (14.7%; 7.1%; 4.0%). The study revealed no difference in the presence of neonatal complications but differences in birth weight (3372.2 ± 552.2 vs. 3415.6 ± 529.0 vs. 3199.0 ± 560.5 g). Gestational diabetes, characterized by FPG ≥ 5.1 mmol/L in early pregnancy, is associated with higher body weight and BMI at the beginning of pregnancy as well as with a higher risk for insulin therapy and increased birth weight.

Copaiba oleoresin presents anti-obesogenic effect and mitigates inflammation and redox imbalance in adipose tissue

ABSTRACT Obesogenic diets lead to fat accumulation and dysfunctional adipose tissue. Active compounds were described in copaiba oleoresin, which presents anti-inflammatory, antimicrobial, and antioxidant properties. However, there are no data regarding the effects of copaiba oleoresin in adipose tissue. Therefore, we tested the hypothesis that the copaiba oleoresin could prevent or minimize obesity and adipose tissue inflammation and oxidative stress in response to a high sucrose diet. Male Wistar rats were randomly assigned to receiving commercial chow (C, n = 8), commercial chow and 30% sucrose added to the drinking water (S, n = 8), or commercial chow and 30% sucrose added to the drinking water + copaiba oleoresin (S+CO, n = 8). Copaiba oleoresin was given at a dose of 200 mg kg-1 day-1 by gavage for eight weeks. C and S animals received vehicle, at equivalent volume, by gavage. At the end of the experiment, blood samples and epididymal adipose tissue were collected for biochemical, inflammatory, and oxidative stress analyses. Copaiba oleoresin supplementation prevented weight gain, adiposity, insulin resistance, and increased IL-1β levels. Additionally, copaiba oleoresin partially attenuated the increase in fasting glucose levels, lipids, and IL-6 levels, and improved the redox status in adipose tissue. Our results suggest that the use of copaiba oleoresin could be a good strategy for prevention of obesity and its complications.

Effects of PPARG and PPARGC1A gene polymorphisms on obesity markers.

Pediatric obesity presents a multifactorial etiology, which involves genetic traits as well, including single nucleotide polymorphisms. The aim of the study is to investigate the contribution of PPARG gene polymorphisms (namely Pro12Ala rs1801282, His447His rs3856806, and Pro115Gln rs1800571) and PPARGC1A rs8192678 SNP on the anthropometric and metabolic parameters in a population of Romanian children. We conducted a cross-sectional study of 295 Caucasian children, divided according to the body mass index (BMI) z-score into the study (obese and overweight) group of 130 children and the control (normoponderal) group of 165 children. Anthropometric parameters were greater in the obese and overweight population as opposed to controls, with significant differences (p < 0.01) found for the weight (2.77 ± 1.54 SD vs. -0.04 ± 1.15 SD), body mass index (BMI) (2.28 ± 0.97 SD vs. -0.18 ± 1.19 SD), mid-upper arm circumference (MUAC) (4.59 ± 2.28 SD vs. 0.28 ± 3.45 SD), tricipital skin-fold (TSF) (3.31 ± 3.09 SD vs. 0.62 ± 7.28 SD) and waist-to-height ratio (WHtR) (0.61 ± 1.51 SD vs. -0.35 ± 1.35 SD) z-scores. Moreover, triglyceride values were higher in the study group (118.70 ± 71.99 SD vs. 77.09 ± 37.39 SD). No significant difference in the allele and genotype distribution of investigates gene polymorphisms was observed between the studied groups (p > 0.05). PPARG (rs1801282, rs3856806, and rs1800571) were not associated with demographic, anthropometric, and laboratory parameters. However, PPARGC1A rs8192678 CC genotype was associated with TSF z-score (p = 0.03), whereas total and LDL cholesterol levels were significantly higher among TT homozygotes (p < 0.01). Our data suggest that PPARG (rs1801282, rs3856806, and rs1800571) and PPARGC1A (rs8192678) gene polymorphisms were not associated with childhood and adolescence overweight and obesity. The present study identified a significant increase in fasting glucose levels, triglyceride, albumin, and ALT levels in children with excess weight, as well as expected important upward variation of anthropometric parameters (BMI, MUAC, TSF z-scores).

Exposure to a hypercaloric diet produces long lasting changes in motivation

Changes in motivation have been observed following induction of diet-induced obesity. However, to date, results have been contradictory, some authors reporting an increase in motivation to obtain palatable food, but others observing a decrease. Observed differences might be associated with the length of both the evaluation period and exposure to the diet. Therefore, the aim of this study was to evaluate changes in motivation during 20 weeks of exposure to a hypercaloric diet. Performance of the subjects in a progressive ratio schedule was evaluated before and during the exposure to a high-fat, high-sugar choice diet (HFHSc). A decrease in motivation was observed after 2 weeks of diet exposure, low levels of motivation remained throughout 20 weeks. A comparable decrease in motivation took longer (3 weeks) to develop using chow diet in the control group. Overall, our results suggest that, when changes in motivation are being evaluated, long periods of diet exposure made no further contribution, once motivation decreased, it remained low up to 18 weeks. Exposure to a HFHSc diet is a useful animal model of obesity, since it replicates some pathophysiological and psychological features of human obesity such as an increase in fasting glucose levels, body weight and the weight of adipose tissue.

Study of LHCGR gene variants in a sample of colombian women with polycystic ovarian syndrome: A pilot study

PurposeTo evaluate the association between polymorphisms of the LHCGR gene and PCOS in a sample from Colombian women. MethodsWe included 49 Colombian women with PCOS and 49 healthy women. Genotype distributions between groups were compared, and phenotype-genotype association analysis was performed in the PCOS group. Identification of five SNP’s in the LHCGR gene was carried out through the iPLEX and MassARRAY system (Agena Bioscience). ResultsOur results showed that the rs7371084 variant was negatively associated with PCOS under the codominant, dominant, and overdominant models. Women with the TC + TT genotypes in rs2293275 had shorter menstrual cycles (p = 0.026), and women with the CT + CC genotypes in rs6732721 showed a decrease in the number of antral follicles (p = 0.038).Within the endocrine parameters, we identified associations between GA + GG genotypes in rs13405728 and CT + CC genotypes in rs6732721, and the decrease in LH levels (p = 0.013; p = 0.04, respectively). Women with TC + TT genotypes in rs2293275 had increased DHEAS (p = 0.047) and androstenedione (p = 0.045) levels. Regarding metabolic parameters, we identified associations between GA + GG genotypes in rs13405728 and CT + CC genotypes in rs6732721, and an increase in fasting glucose levels (p = 0.028; p = 0.017, respectively). ConclusionWe found that the rs7371084 variant was negatively associated with PCOS. Also, we identify associations between combined genotypes of the LHCGR gene and the phenotypic traits of PCOS, such as shorter menstrual cycle length, fewer follicles, lower LH levels, and increased DHEAS, androstenedione, and fasting glucose levels. The results of this pilot study provide a basis to clarify the genetics and pathophysiology of PCOS in the Colombian population. Future large-scale studies are recommended for this population.

Relationships between fasting glucose levels, lifestyle factors, and metabolic parameters in Korean adults without diagnosis of diabetes mellitus.

BackgroundWe investigated the associations between fasting glucose level ranges with lifestyle factors and metabolic profiles among adults without previous diagnosis of diabetes.MethodsWe analyzed 13 625 adults without previous diagnosis of diabetes from the Korea National Health and Nutrition Examination Survey during 2016 to 2018. We categorized fasting glucose levels (mg/dl) as follows: <90, 90 to 99, 100 to 109, 110 to 124, and ≥125. We evaluated trends in the proportions of individuals with obesity, abdominal, obesity, current smoking, heavy drinking, and low physical activity according to these categories, and the odds for uncontrolled blood pressure (BP), low‐density lipoprotein cholesterol (LDL‐C), triglycerides (TG), and high‐density lipoprotein cholesterol (HDL‐C) for each fasting glucose level compared to a fasting glucose level of <90 mg/dl.ResultsThe proportions of individuals with obesity, abdominal obesity, and heavy drinking increased according to fasting glucose level (P for trend <.05). The odds for BP ≥140/90 mm Hg, TG ≥150 mg/dl, HDL‐C < 40 mg/dl in men, and HDL‐C < 50 mg/dl in women increased with increasing fasting glucose levels; however, the odds for LDL‐C ≥ 130 mg/dl increased with increasing fasting glucose levels only in women. The increases in odds for uncontrolled BP and lipid profiles were mostly observed for fasting glucose levels ≥90 mg/dl.ConclusionsEfforts are needed to prevent increased fasting glucose levels, as higher levels, even within normal range, were associated with poor metabolic profiles.

Abstract 14193: Bmp-7 Ameliorates Lipid Accumulation Induced, Hmgb1 Initiated Pyroptosis Leading To Sarcopenia, Muscle Deterioration And Adverse Muscle Remodeling In Diabetes

Introduction: Diabetic muscle myopathy involves hyperglycemia and inflammation that causes skeletal muscle dysfunction. However, the potential cellular mechanisms that occur during hyperglycemia and inflammation, which induces sarcopenia, muscle deterioration and muscle dysfunction remains unknown. Hypothesis: We hypothesize that, Bone morphogenetic protein-7 (BMP-7) ameliorates hyperlipidemia induced inflammation and pyroptosis in the development and progression of diabetic myopathy. Methods: C57BL6 mice were treated with saline, streptozotocin (STZ), or STZ+BMP-7 to generate diabetic muscle myopathy. Diabetes was established by increased fasting glucose levels and GTT. Gastrocnemius muscle and blood samples were collected. Blood was used to determine the lipid levels. Skeletal muscle was used to investigate lipid accumulation, pyroptosis, muscle deterioration, atrophy, and adverse structural remodeling using histology, immunohistochemistry, western blot, and RT-PCR. Results: We observed a significant ( p &lt;0.05) increase in blood glucose and serum lipid levels in diabetic animals. A significant ( p &lt;0.05) increase in hyperglycemia lead an increase in lipid accumulation, inflammasome formation and further an up-regulation of the downstream pyroptotic markers as well as signaling markers [TGFβ, Smad2 and Smad3] in diabetic muscle cells. Structural analysis showed the significant ( p &lt;0.05) loss of muscle weight, decreased myofibrillar area, increased muscle deterioration and fibrosis leading to muscle dysfunction. Whereas, BMP-7 attenuated hyperglycemia, hyperlipidemia, lipid accumulation, inflammation, pyroptosis, signaling markers and diabetic adverse structural modifications resulting in significantly ( p &lt;0.05) improved muscle function. Conclusion: We report for the first time that increased hyperlipidemia aggravates inflammation involved cellular pyroptosis that induces significant muscle cell loss and adverse remodeling in diabetic muscle myopathy. Targeting pyroptosis and lipid accumulation in muscle cells, with BMP-7 improves diabetic muscle pathophysiology and muscle function. These findings shows BMP-7 as a potential therapeutic option to treat diabetic myopathy.

Beet (Beta vulgaris) Improve Blood Glucose and AKT2 Gene Expression in High Fat and Fructose-induced Rats

ABSTRACT&#x0D; Background: Diet components significant effects on glucose homeostasis. A diet contains high saturated fat and fructose induces insulin resistance and enhanced blood glucose. In contrast, food containing flavonoids such as beet can improve glucose homeostasis via modulation of gene expression, e.g., AKT2, involving glucose metabolism.&#x0D; Aims: This study were to evaluate the benefit of beet on AKT2 gene expression and fasting glucose.&#x0D; Methods: Twenty wistar male was divided into five groups: Normal were fed a normal diet, group HFFD was given a diet containing high fat and fructose, and three groups (HFB1, HFB2, HFB3) were given a diet containing high fat and fructose for eight weeks and continuous fed beet-contained normal diet for six weeks. The percentage of beet in the diet for each 6%, 9%, and 12%, respectively.&#x0D; Results: The fasting glucose was measured before and after the intervention, whereas the gene expression of AKT2 at skeletal muscle tissue was determined after the intervention. A diet high in fat and fructose increased fasting glucose levels, and a beet-contained diet decreased it.&#x0D; Conclusions: The beet 9% substituted diet can improve glucose homeostasis from the effects of a high fat and fructose diet, and the expression of the AKT2 gene may have a role in the process.&#x0D; Keywords: AKT2, Antioxidant, Beet, Fat, Fructose.

Effect of time-restricted feeding on body composition and cardio-metabolic risk in middle-aged women in Taiwan

Objectives: We sought to investigate the effects of time-restricted feeding (TRF) and a traditional weight-loss method on body composition and cardio-metabolic risk factors in middle-aged women.Methods: In a single-center, randomized, open-label, parallel-group design, women ages 40 to 65 y with body mass index ≥ 24 kg/m2 or waist circumference > 80 cm were recruited. They were guided to a daily low-calorie diet of 1400 kcal and randomly assigned into a TRF group (limit 8 h of eating time and fasting for 16 h) or a non-TRF group (traditional weight-loss method, unrestricted eating time) for 8 wk. Body composition, blood pressure, blood biochemical variables, and insulin resistance status were measured before and after intervention.Results: Body weight, body mass index, waist circumference, and body fat mass decreased significantly in both groups after 8 wk of intervention (P < 0.05). Body weight decreased more in the TRF group than the non-TRF group (−4.1% ± 2.8% versus −2.4% ± 2.5%; P = 0.012), as did diastolic blood pressure (75.3 ± 11.2 mm Hg versus 70.5 ± 9.4 mm Hg; P = 0.012). There were no statistical differences between the two groups in total cholesterol, triacylglycerols, high- or low-density lipoprotein cholesterol, and fasting insulin level. However, fasting glucose and insulin resistance status increased significantly for the TRF group after the intervention (respectively, 88.3 ± 7.6 mg/dL versus 92.6 ± 9.6 mg/dL, P = 0.003; 1.7 ± 0.7 versus 2.1 ± 1.0, P = 0.048).Conclusion: The weight loss and reduction in diastolic blood pressure using the TRF method were better than with the traditional weight-loss method. However, this method may increase fasting glucose levels and adverse insulin resistance status.

Abstract P319: SARM1 NAD Hydrolase Deficiency Protects Hearts Against Diabetic Cardiomyopathy

NAD depletion is associated with the pathogenesis of diseases such as heart failure. Strategies to replenish cellular NAD levels by activating NAD synthesis pathways have shown promises to treat heart disease. However, how NAD consumption mechanisms lead to NAD depletion are less understood. SARM1 is a novel intracellular NAD hydrolase that degrades NAD and promotes axonal degeneration in neurons. We recently showed that NAD redox imbalance and depletion promote the progression of diabetic cardiomyopathy. Therefore, we hypothesized that SARM1 deficiency might protect hearts against diabetic cardiomyopathy. 16-week diabetic stress initiated by streptozotocin (STZ) injections was applied to wild-type C57BL/6 (WT) and whole-body SARM1-KO mice. Cardiac function was measured after 8-week or 16-week of diabetic stress, and cardiac tissue and plasma samples from these mice were harvested after 16 weeks of diabetes. SARM1 mRNA or protein levels were suppressed in SARM1-KO hearts. STZ induced similar hyperglycemia (~600 mg/dL) in both WT and SARM1-KO male mice after 16 weeks. Chronic diabetic stress led to progressive decline in systolic function (Baseline fractional shortening: 50%; 16-week diabetes: 35%; P&lt;0.05; n=5) in WT male mice, which was ameliorated in SARM1-KO male mice (16-week diabetes: 48%; P&lt;0.05; n=5). Progressive decline in diastolic function induced by chronic diabetes (Baseline WT E’/A’: 1.53; WT 16-week diabetes: 1.12; n=5) was also improved in diabetic SARM1-KO mice (KO E’/A’ ratio at 16-week diabetes: 1.5; P&lt;0.05; n=5). Heart weights were similar in diabetic WT or diabetic SARM1-KO hearts. A similar study is on-going in a female cohort. Despite loss of SARM1 expression, no compensatory changes in expressions of other NAD hydrolases (i.e. Cd38 or Bst1) were observed in diabetic SARM1-KO hearts, while expression levels of genes related to NAD consumption and synthesis pathways were mostly unchanged except Qprt and Haao. Cardiac fibrosis was induced in diabetic WT hearts and were suppressed in diabetic SARM1-KO hearts after 16-week diabetic stress, but these changes were not observed in tissues harvested after 8-week diabetic stress. The results suggest fibrosis is a later event in the progression of diabetic cardiomyopathy. WT and SARM1-KO mice have also been challenged with high fat diet feeding (HFD) for 16 weeks, and increased fasting glucose levels and body weights were similarly observed in HFD-WT and HFD-SARM1-KO mice. Longitudinal cardiac function analyses are on-going. Our data thus far support the protective role of SARM1 deficiency in metabolic stress-induced cardiomyopathy, while pathogenic mechanisms of SARM1 in diabetic hearts remain to be determined.

Circadian rhythm disruption with high-fat diet impairs glycemic control and bone quality.

Biological functions, including glycemic control and bone metabolism, are highly influenced by the body's internal clock. Circadian rhythms are biological rhythms that run with a period close to 24hours and receive input from environmental stimuli, such as the light/dark cycle. We investigated the effects of circadian rhythm disruption (CRD), through alteration of the light/dark schedule, on glycemic control and bone quality of mice. Ten-week-old male mice (C57/BL6, n=48) were given a low-fat diet (LFD) or a high-fat diet (HFD) and kept on a dayshift or altered schedule (RSS3) for 22weeks. Mice were divided into four experimental groups (n=12/group): Dayshift/LFD, Dayshift/HFD, RSS3/LFD, and RSS3/HFD. CRD in growing mice fed a HFD resulted in a diabetic state, with a 36.2% increase in fasting glucose levels compared to the Dayshift/LFD group. Micro-CT scans of femora revealed a reduction in inner and outer surface expansion for mice on a HFD and altered light schedule. Cancellous bone demonstrated deterioration of bone quality as trabecular number and thickness decreased while trabecular separation increased. While HFD increased cortical bone mineral density, its combination with CRD reduced this phenomenon. The growth of mineral crystals, determined by small angle X-ray scattering, showed HFD led to smaller crystals. Considering modifications of the organic matrix, regardless of diet, CRD exacerbated the accumulation of fluorescent advanced glycation end-products (fAGEs) in collagen. Strength testing of tibiae showed that CRD mitigated the higher strength in the HFD group and increased brittleness indicated by lower post-yield deflection and work-to-fracture. Consistent with accumulation of fAGEs, various measures of toughness were lowered with CRD, but combination of CRD with HFD protected against this decrease. Differences between strength and toughness results represent different contributions of structural and material properties of bone to energy dissipation. Collectively, these results demonstrate that combination of CRD with HFD impairs glycemic control and have complex effects on bone quality.