Blood Levels Of Fasting Glucose Research Articles

Impaired hepatic glucose metabolism and liver-α-cell axis in mice with liver-specific ablation of the Hepatocyte Nuclear Factor 4α (Hnf4a) gene

BackgroundHnf4a gene ablation in mouse liver causes hepatic steatosis, perturbs HDL structure and function and affects many pathways and genes related to glucose metabolism. Our aim here was to investigate the role of liver HNF4A in glucose homeostasis. MethodsSerum and tissue samples were obtained from Alb-Cre;Hnf4afl/fl (H4LivKO) mice and their littermate Hnf4afl/fl controls. Fasting glucose and insulin, glucose tolerance, insulin tolerance and glucagon challenge tests were performed by standard procedures. Binding of HNF4A to DNA was assessed by chromatin immunoprecipitation assays. Gene expression analysis was performed by quantitative reverse transcription PCR. ResultsH4LivKO mice presented lower blood levels of fasting glucose, improved glucose tolerance, increased serum lactate levels and reduced response to glucagon challenge compared to their control littermates. Insulin signaling in the liver was reduced despite the increase in serum insulin levels. H4LivKO mice showed altered expression of genes involved in glycolysis, gluconeogenesis and glycogen metabolism in the liver. The expression of the gene encoding the glucagon receptor (Gcgr) was markedly reduced in H4LivKO liver and chromatin immunoprecipitation assays revealed specific and strong binding of HNF4A to the Gcgr promoter. H4LivKO mice presented increased amino acid concentration in the serum, α-cell hyperplasia and a dramatic increase in glucagon levels suggesting an impairment of the liver-α-cell axis. Glucose administration in the drinking water of H4LivKO mice resulted in an impressive extension of survival. The expression of several genes related to non-alcoholic fatty liver disease progression to more severe liver pathologies, including Mcp1, Gdf15, Igfbp-1 and Hmox1, was increased in H4LivKO mice as early as 6 weeks of age and this increased expression was sustained until the endpoint of the study. ConclusionsOur results reveal a novel role of liver HNF4A in controlling blood glucose levels via regulation of glucagon signaling. In combination with the steatotic phenotype, our results suggest that H4LivKO mice could serve as a valuable model for studying glucose homeostasis in the context of non-alcoholic fatty liver disease.

Ejercicio aeróbico y dieta baja en hidratos de carbono en la obesidad: estudio de caso

Objectives. To compare the efficacy of low carbohydrate diet and aerobic exercise alone or combined for the treatment of obesity and metabolic syndrome in a subject without other comorbilities.Methodology. An intervention based on aerobic exercise and low carbohydrate diet both alone and combined was used as a treatment for obesity and metabolic syndrome in an otherwise healthy subject. Parameters related to these pathologies such as body fat percentage, lipid profile, fasting glucose or body mass index were registered.Results. Both the combined program and nutritional intervention induced reductions in total weight, body mass index, waist to hip ratio, total cholesterol, triglycerides and fasting glucose blood levels. The intervention based only on aerobic exercise did not result in any improvement.Conclusions. A combination of aerobic exercise together with a low carbohydrate diet was effective for the treatment of obesity and metabolic syndrome in this case. The intervention based on the low carbohydrate diet was also effective. The intervention based only on aerobic exercise did not provide any beneficial results, contrary to the results obtained by previous research. More research with larger samples and especially including a control group is needed in order to evaluate whether the results obtained in this study could be extrapolated to the general obese population.

Effects of standardized hydro-alcoholic extract of Vaccinium arctostaphylos leaf on hypertension and biochemical parameters in hypertensive hyperlipidemic type 2 diabetic patients: a randomized, double-blind and placebo-controlled clinical trial.

To study the blood pressure, lipid and glycemic effects and safety of Vaccinium arctostaphylos leaf in the hypertensive hyperlipidemic type 2 diabetic patients. The patients took 350 mg standardized plant leaf hydro-alcoholic extract capsule (n=50) or placebo capsule (n=50) three times daily alongside conventional drugs for 2 months. At the baseline and endpoint, systolic and diastolic blood pressures and blood levels of fasting glucose (FG), 2-hr postprandial glucose (2hPPG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), LDL-C, triglyceride, HDL-C, SGOT, SGPT and creatinine were determined in both groups. To evaluate the extract safety, serum SGOT, SGPT and creatinine levels were tested; also, the patients were requested to report any adverse effects. FG, 2hPPG, HbA1c, TC, LDL-C, triglyceride and systolic and diastolic blood pressures were decreased, whereas HDL-C was increased significantly in the extract group compared to those of the placebo group at the endpoint (for all cases, p<0.05). The extract did not significantly influence other parameters and no adverse effects were reported. V. arctostaphylos leaf hydro-alcoholic extract as an adjunct to the conventional drugs has additional antihypertensive as well as anti-dyslipidemic and anti-hyperglycemic effects in hypertensive hyperlipidemic type 2 diabetic patients. Besides, the extract lacks hepatic, renal and patient-reported adverse effects.

Risk of Breast Cancer According to Glycaemia and HbA1c Concentration—A Meta-analysis of Prospective Studies

Some observational studies have suggested that women with diabetes may be at increased risk of breast cancer. Blood levels of fasting glucose (FG) and of glycated hemoglobin (HbA1c) are major diagnostic tools for diabetes. The aim of this study was to investigate the association between HbA1c, FG and breast cancer occurrence. A systematic literature search identified prospective studies which reported a quantitative estimate of the association between HbA1c or FG and breast cancer. Summary relative risks (SRR) of breast cancer, comparing high vs. low levels of HbA1c or FG, were computed using random-effect meta-analysis. Ten studies for HbA1c (116,035 women and 3,095 breast cancer cases) and 13 studies for FG (971,071 women and 14,579 breast cancer cases) were selected. High levels of HbA1c (FG) ranged from &amp;gt;4.5% to &amp;gt;9% (&amp;gt;5 to &amp;gt;7.8 mmol/L), and low level ranged from &amp;lt;4.3% to &amp;lt;6.7% (&amp;lt;4.4 to &amp;lt;6.1 mmol/L). Overall, the SRR of breast cancer was 0.97 (95% CI: 0.76, 1.24) for HbA1c and 1.15 (95% CI: 1.00, 1.33) for FG, with moderate heterogeneity between studies (I²=44% and 45%, respectively). When the analyses were restricted to women with HbA1c &amp;lt;6.5% and FG &amp;lt;7mmol/L, the SRR was 0.97 (95% CI: 0.81, 1.15) for HbA1c (six studies) and 1.15 (95% CI: 1.01, 1.31) for FG (seven studies) without heterogeneity in both analyses (I²=0%). In 3 studies conducted in diabetic women, the SRR for the association between HbA1c levels and breast cancer was 0.95 (95% CI: 0.79, 1.15) with no heterogeneity (I2=0%). No study was found on FG among diabetic women only. No association was found between HbA1c and breast cancer occurrence, while fasting glucose might be associated with a slight increased risk. The lack of clear association suggests that the increased risk of breast cancer observed among diabetic women appears to be driven by factors other than the blood glucose concentration disorders. Disclosure A. Macacu: None. C. Pizot: None. P. Boyle: Other Relationship; Self; Sanofi. P. Autier: Other Relationship; Self; Sanofi.

Psychomotor Vigilance Test and Its Association With Daytime Sleepiness and Inflammation in Sleep Apnea: Clinical Implications.

Excessive daytime sleepiness (EDS) is a key symptom of obstructive sleep apnea (OSA). The Psychomotor Vigilance Task (PVT) has been suggested as an objective easy-to-use, inexpensive alternative to the Multiple Sleep Latency Test (MSLT) to measure EDS. In patients with OSA, physiological sleepiness, but not subjective EDS (Epworth Sleepiness Scale [ESS]), has been associated with increased levels of the sleep- inducing proinflammatory cytokine interleukin-6 (IL-6). The goal of this study was to assess the association of PVT with objectively measured sleepiness (MSLT) and subjectively measured sleepiness (ESS) and IL-6 levels in patients with OSA. We studied 58 untreated patients with OSA who underwent an 8-hour in-laboratory polysomnography for 4 consecutive nights. MSLT, PVT, and 24-hour serial profiles of IL-6 were assessed on the fourth day. PVT variables included number of lapses, mean reciprocal of the fastest 10% and slowest 10% reaction times, and median of 1/reaction time. ESS was assessed on day 1 of the study. Higher ESS scores were significantly associated with greater number of lapses (β = .34, P = .02) and lower values of 1/RT (β = -.36, P = .01) and slowest 10% RTs (β = -.30, P = .04). No significant association was observed between PVT and MSLT, nor PVT and IL-6 levels. Our findings suggest that PVT is associated with subjectively assessed daytime sleepiness, but not with physiological sleepiness nor IL-6 levels in patients with OSA. It appears that ESS and PVT may be useful in predicting risks associated with impaired performance, such as traffic accidents, in patients with OSA.

Non-Muscle Myosin Heavy Chain 9 Gene (MYH9) Polymorphism (rs4821481) is Associated with Urinary Albumin Excretion in Iranian Diabetic Patients

Background: Myosin heavy chain 9 (MYH9) gene polymorphisms have been implicated in different types of renal disease, as well as in nephropathy attributed to type 2 diabetes mellitus. Objectives: This study sought to analyze the association of MYH9 gene polymorphism (rs4821481) with diabetic nephropathy (DN), urine albumin excretion value, and glomerular filtration rate (GFR) in an Iranian diabetic population. Methods: This case-control study included 201 diabetic patients with and without DN, who were referred to the diabetes and metabolic center, Tehran, Iran. The allele and genotype frequencies of rs4821481 were determined using ARMS-polymerase chain reaction (ARMS-PCR). In both groups, blood levels of fasting glucose, HbA1c, urea, creatinine, uric acid, and lipids, as well as urine albumin and creatinine, were measured and GFR was calculated. Results: Patients who carried the rs4821481 polymorphism had significantly higher urinary excretion of albumin (P < 0.05) and insignificantly lower GFR values (P = 0.08). The frequency of rs4821481 SNP was 22.8 in patients without DN versus 28 in the DN group, which was not statistically significant. Only 2 and 3 of patients without DN and with DN, respectively, had two copies of the C allele. No significant association was found between the rs4821481 polymorphism and DN (OR 95% CI 1.56 0.79 - 3.08, P = 0.19). Conclusions: Although we found an association between MYH9 gene polymorphism and urinary albumin excretion, the results did not show a significant association between MYH9 polymorphism (rs4821481) and risk of DN in Iranian diabetic patients. A¯Â?½ 2016, Iranian Red Crescent Medical Journal.

Salvia officinalis (Sage) Leaf Extract as Add-on to Statin Therapy in Hypercholesterolemic Type 2 Diabetic Patients: a Randomized Clinical Trial.

The efficacy and safety of Salvia officinalis combined with statin have not been evaluated in dyslipidemic diabetes mellitus type 2 (DDMT2) so far. The plant extract antioxidant activity was determined by the DPPH radical scavenging assay. The total flavonoid, total phenolic and quercetin contents of the capsules containing the plant extract were also measured. Moreover, the effects of 2-month extract intake (500 mg capsule three times a day) as add-on to daily use of 15 mg glyburide, 2000 mg metformin and 10 mg atorvastatin on the blood levels of fasting glucose (FG), 2 h postprandial glucose (2hPPG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride, high-density lipoprotein cholesterol (HDL-C), serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), creatinine and body mass index were studied in 50 patients and compared with the placebo group (n=50).The extract IC50 in the DPPH assay was 87.26±0.003 µg/mL (mean±SD), whereas the ascorbic acid IC50 was 5.626± 0.001 µg/mL (mean±SD). The total flavonoid, total phenolic and quercetin contents of the capsule containing the plant extract were 39.76±3.58 mg of rutin equivalents (mean±SD), 30.33±1.23 mg of gallic acid (mean±SD) and 0.13 mg, respectively. The extract lowered FG, 2hPPG, HbA1c, TC, LDL-C and triglyceride levels, but increased HDL-C level compared to the placebo at the endpoint (P<0.05). The extract did not affect the other parameters significantly and no adverse effect was reported. The extract has substantial antioxidant activity which may be beneficial for the prevention of the cardiovascular complications of DDMT2. Moreover, addition of the extract to statin therapy is apparently safe and further improves lipid profile.

The diet-induced metabolic syndrome is accompanied by whole-genome epigenetic changes.

Consuming a high-fat/high-fructose diet (HFD) starting at a young age leads to the development of obesity and to the progression of metabolic syndrome (MS). We are interested in the relationship between MS and DNA methylation as a mediator of the metabolic memory and the early appearance of these diseases in the progeny. To this end, Wistar rats were fed a HFD for 1year, and every 12weeks, biochemical analyses were performed. After 24weeks, animals fed the HFD showed alterations related to MS such as elevated blood levels of fasting glucose, triglycerides, and insulin compared with their littermate controls. During the experimental period, the control females exhibited a 40% lower 5-methylcytosine (5-mC) level compared to the control males. The HFD affected the 5-mC levels in males and females differently. The HFD induced a 20% decrease in the 5-mC levels in males and a 15% increase in females. We found that the HFD induces an early presentation of MS in the progeny of treated animals and that the DNA methylation was altered in the F1 generation. The presentation of MS is positively associated with changes in the global percentage of 5-mC in the DNA.

Anti-Hyperglycemic Effect of Vaccinium arctostaphylos in Type 2 Diabetic Patients: A Randomized Controlled Trial

Background: Type 2 diabetes mellitus is a common disease. Preliminary data indicate that Vaccinium arctostaphylos L. (Caucasian whortleberry) has a potential effect in glycemic control. Thus, the efficacy and safety of a standardized whortleberry fruit hydroalcoholic extract in the treatment of type 2 diabetic patients were studied. Methods: This randomized double-blind placebo-controlled clinical trial consisted of 37 patients aged 40-60 years with type 2 diabetes who were resistant to conventional oral anti-hyperglycemic drugs. The patients were treated with the whortleberry fruit hydroalcoholic extract (1 capsule = 350 mg, every 8 h for 2 months) in combination with anti-hyperglycemic drugs, and the effects on the blood levels of fasting glucose, 2-hour postprandial glucose, glycosylated hemoglobin (HbA1c), and liver/kidney function were tested, evaluated, and compared with a placebo group (n = 37). Results: The extract significantly lowered the blood levels of fasting glucose, 2-h postprandial glucose, and HbA1c (p = 0.007, p <0.001, and p = 0.005, respectively) without any significant effects on the liver/kidney function (p >0.05) compared with placebo at the end. No adverse effects were reported. Conclusion: Whortleberry may safely improve glycemic control in type 2 diabetic patients.

Improved Glycemic Control in Patients with Advanced Type 2 Diabetes Mellitus Taking Urtica dioica Leaf Extract: A Randomized Double-Blind Placebo-Controlled Clinical Trial

Advanced type 2 diabetes mellitus (T2DM) needing insulin therapy is common. Most conventional anti-hyperglycemic drugs have limited efficacies and significant side effects, so that better anti-hyperglycemic agents are needed. Urtica dioica L. (nettle) leaves have insulin secretagogue, PPARgamma agonistic, and alpha-glucosidase inhibitory effects. Moreover, nettle leaves are used in traditional medicine as an anti-hyperglycemic agent to treat diabetes mellitus. Thus, efficacy and safety of nettle in the treatment of patients with advanced type 2 diabetes mellitus needing insulin were studied. In this randomized double-blind placebo-controlled clinical trial, we evaluated the effects of taking nettle leaf extract (one 500 mg capsule every 8 hours for 3 months) combined with the conventional oral anti-hyperglycemic drugs on the blood levels of fasting glucose, postprandial glucose, glycosylated hemoglobin (HbA1c), creatinine and liver enzymes SGOT and SGPT, and systolic and diastolic blood pressures in 46 patients and compared with the placebo group (n = 46). At the endpoint, the extract lowered the blood levels of fasting glucose, 2 hours postprandial glucose, and HbA1c significantly (p < 0.001, p = 0.009, and p = 0.006, respectively) without any significant effects on the other parameters (p > 0.05) compared with placebo. Nettle may safely improve glycemic control in type 2 diabetic patients needing insulin therapy.

Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: A randomized controlled trial

AimsCoronary artery disease (CAD) is associated with endothelial dysfunction and mitochondrial dysfunction (MD). The aim of this study was to investigate whether co-enzyme Q10 (CoQ) supplementation, which is an obligatory coenzyme in the mitochondrial respiratory transport chain, can reverse MD and improve endothelial function in patients with ischaemic left ventricular systolic dysfunction (LVSD). Methods and resultsWe performed a randomized, double-blind, placebo-controlled trial to determine the effects of CoQ supplement (300mg/day, n=28) vs. placebo (controls, n=28) for 8weeks on brachial flow-mediated dilation (FMD) in patients with ischaemic LVSD(left ventricular ejection fraction <45%). Mitochondrial function was determined by plasma lactate/pyruvate ratio (LP ratio). After 8weeks, CoQ-treated patients had significant increases in plasma CoQ concentration (treatment effect 2.20μg/mL, P<0.001) and FMD (treatment effect 1.51%, P=0.03); and decrease in LP ratio (treatment effect −2.46, P=0.03) compared with controls. However, CoQ treatment did not alter nitroglycerin-mediated dilation, blood pressure, blood levels of fasting glucose, haemoglobin A1c, lipid profile, high-sensitivity C-reactive protein and oxidative stress as determined by serum superoxide dismutase and 8-isoprostane (all P>0.05). Furthermore, the reduction in LP ratio significantly correlated with improvement in FMD (r=−0.29, P=0.047). ConclusionIn patients with ischaemic LVSD, 8weeks supplement of CoQ improved mitochondrial function and FMD; and the improvement of FMD correlated with the change in mitochondrial function, suggesting that CoQ improved endothelial function via reversal of mitochondrial dysfunction in patients with ischaemic LVSD.