EFFECT OF EXERCISE ON INSULIN RESISTANCE IN OBESE TYPE 2 DIABETES PATIENTS

ABSTRACT Introduction: Type 2 diabetes mellitus (T2DM), also known as non-insulin-dependent diabetes mellitus (NIDDM), accounts for more than 90% of the total number of diabetes mellitus cases and often occurs in middle-aged and elderly people. Objective: To investigate the effect of exercise intervention on insulin resistance in obese type 2 diabetes patients. Methods: Eighty-six obese diabetic patients were screened as experimental subjects in physical examinations and randomly divided into observation and control groups. Visceral fat volume, fasting blood glucose, and fasting insulin of all subjects were measured before and after completion of the 6-month experimental implementation. The insulin resistance was calculated for both groups and the values for each indicator were compared statistically between groups. Results: Control of body weight, body mass index, blood glucose, blood lipids and insulin resistance index were better in the observation group than in the control group, and the difference was statistically significant (P < 0.05). Conclusions: Basal intervention with quantitative exercise can significantly improve insulin resistance in obese type 2 diabetes patients and the effect is better than treatment with diet and conventional exercise. Level of evidence II; Therapeutic studies - investigation of treatment results.

DPHC From Alpinia officinarum Ameliorates Oxidative Stress and Insulin Resistance via Activation of Nrf2/ARE Pathway in db/db Mice and High Glucose-Treated HepG2 Cells

(R)-5-hydroxy-1,7-diphenyl-3-heptanone (DPHC) from the natural plant Alpinia officinarum has been reported to have antioxidation and antidiabetic effects. In this study, the therapeutic effect and molecular mechanism of DPHC on type 2 diabetes mellitus (T2DM) were investigated based on the regulation of oxidative stress and insulin resistance (IR) in vivo and in vitro. In vivo, the fasting blood glucose (FBG) level of db/db mice was significantly reduced with improved glucose tolerance and insulin sensitivity after 8 weeks of treatment with DPHC. In vitro, DPHC ameliorated IR because of its increasing glucose consumption and glucose uptake of IR-HepG2 cells induced by high glucose. In addition, in vitro and in vivo experiments showed that DPHC could regulate the antioxidant enzyme levels including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), thereby reducing the occurrence of oxidative stress and improving insulin resistance. Western blotting and polymerase chain reaction results showed that DPHC could promote the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), the heme oxygenase-1 (HO-1), protein kinase B (AKT), and glucose transporter type 4 (GLUT4), and reduced the phosphorylation levels of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) on Ser307 both in vivo and in vitro. These findings verified that DPHC has the potential to relieve oxidative stress and IR to cure T2DM by activating Nrf2/ARE signaling pathway in db/db mice and IR-HepG2 cells.

Effects of Sambiloto (Andrographis paniculata) on GLP-1 and DPP-4 Concentrations between Normal and Prediabetic Subjects: A Crossover Study

Background. The extract of Andrographis paniculata (Burm. F.) Wall. Ex. Nees. (sambiloto) (穿心蓮 chuān xīn lián) has been reported to have an antidiabetic effect on mice models and has been used traditionally in the community. The exact mechanism of sambiloto extract in decreasing plasma glucose is unclear, so we investigated the role of sambiloto extract in the incretin pathway in healthy and prediabetic subjects. Methods. This study was a randomized, placebo-controlled, crossover, double-blind trial. It included 38 people who were healthy and 35 people who had prediabetes. All subjects were randomly assigned to receive either the intervention sambiloto extract or a placebo. All subjects were randomly assigned to receive the first intervention for 14 days. There was a washout period between subsequent interventions. The primary outcome was glucagon-like peptide 1 (GLP-1) concentration, and secondary outcomes were fasting insulin, 2-hour postprandial insulin, homeostasis model assessment of insulin resistance (HOMA-IR), fasting blood glucose, 2-hour postprandial blood glucose, dipeptidyl peptidase-4 (DPP-4), and glycated albumin before and after the intervention. Result. After the intervention, GLP-1 concentration significantly increased in prediabetes by 19.6% compared to the placebo ( p = 0.043 ). There were no significant differences in the changes of fasting insulin, 2-hour postprandial insulin, HOMA-IR, fasting blood glucose, 2-hour postprandial blood glucose, DPP-4, and glycated albumin levels after the intervention. Sambiloto extract did not inhibit the DPP-4 enzyme in healthy and prediabetic subjects. Conclusion. Sambiloto extract increased GLP-1 concentration without inhibiting the DPP-4 enzyme in prediabetic subjects. This trial is registered with ClinicalTrials.gov (ID: NCT03455049), registered on 6 March 2018—retrospectively registered (https://clinicaltrials.gov/ct2/show/NCT03455049).

Changes in the Prevalence of Hyperuricemia in Clients of Health Examination in Eastern China, 2009 to 2019

Background: With the continuous improvement of people's living standards, the incidence of hyperuricemia (HUA) is increasing globally. The prevalence of HUA ranged in terms of region, race, and age. This study aims to investigate the changes in the prevalence of HUA in clients of health examination in Eastern China between 2009 and 2019. Methods: Chinese men and women aged 20-79 years (n = 4847 in the 2009 cohort and n = 12188 in 2019) who had received health examinations were enrolled. Serum uric acid (UA) levels and biochemical parameters, including fasting blood-glucose (FBG), triglyceride (TG), total cholesterol (CHOL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine (Cr) and blood urea nitrogen (BUN) were evaluated. The prevalence of HUA in different age groups were measured, and the correlation of biochemical parameters with the onset of HUA were analyzed. Results: The prevalence of HUA was 18.7% in the 2019 cohort, which was significantly higher than that in 2009 (13.3%). In females, the prevalence of HUA was significantly higher in 2019 than 2009 for age groups of 20-29 and 30-39 years. In male population, 2019 cohort had significantly higher age-specific prevalence for all age groups than 2009 cohort. Young men aged 20-29 years became the main population of HUA in the 2019 male cohort, whereas middle-aged men aged 40-49 years had the highest prevalence of HUA in the 2009 male cohort. The prevalence rates of HUA in all BMI groups in 2019 cohort were significantly higher than those in 2009 cohort. Spearmen’s correlation analysis and Logistic regression analysis indicated that BMI was positively correlated with the onset of HUA. The receiver-operating characteristic curve (ROC) analysis showed BMI＞24.48kg/m2 and BMI＞23.84 kg/m2 displayed good capacities to discriminate the population with HUA from those without HUA in 2009 and 2019 cohort, respectively. Conclusions: In recent 10 years, the prevalence of HUA was increased rapidly in Chinese adults, especially in males. Young men aged 20-29 years in the 2019 cohort replaced the middle-aged males (40-49 years old) in the 2009 cohort, and became the main population of male HUA in the 2019 cohort. BMI was positively correlated with HUA, and might be a potential risk factors to predict the onset of HUA.

The effect of non-invasively obtained central blood pressure on cardiovascular outcome in diabetic patients in Assiut University Hospitals

Background The major cause of morbidity and mortality in diabetes is cardiovascular disease, which is exacerbated by the presence of hypertension. Therefore, proper control of BP in diabetic hypertensive patients is essential. Few studies have specifically investigated the prognostic significance of central BP in Egyptian populations with diabetes and hypertension and its relation with cardiovascular outcome. This study aims to evaluate relation between central BP and diabetic composite cardiovascular complications. Results Diabetic patients with CVD were significantly older (p value < 0.01), obese (p value < 0.01) with long duration of diabetes (p value < 0.001) and had significantly higher peripheral and central systolic and diastolic BP and higher AIx@75(p values < 0.01) than those without CVD. Regarding the metabolic parameters, they had significantly higher fasting blood glucose, HbA1c, and higher blood cholesterol levels (p values < 0.001), higher LDL (p value < 0.01), triglycerides levels (p value = 0.014), and microalbuminuria (p value = 0.028). Logistic regression analysis found increased BMI, central systolic BP, and AIx@75 were independent predictors of composite CVD (p values < 0.05). Conclusions There is a pattern of favorability towards central rather than peripheral BP indices to predict the occurrence of CVD in diabetic patients.

Clinical Characteristics of COVID-19 Patients in a Regional Population With Diabetes Mellitus: The ACCREDIT Study

ObjectiveTo identify clinical and biochemical characteristics associated with 7- &amp; 30-day mortality and intensive care admission amongst diabetes patients admitted with COVID-19.Research Design and MethodsWe conducted a cohort study collecting data from medical notes of hospitalised people with diabetes and COVID-19 in 7 hospitals within the Mersey-Cheshire region from 1 January to 30 June 2020. We also explored the impact on inpatient diabetes team resources. Univariate and multivariate logistic regression analyses were performed and optimised by splitting the dataset into a training, test, and validation sets, developing a robust predictive model for the primary outcome.ResultsWe analyzed data from 1004 diabetes patients (mean age 74.1 (± 12.6) years, predominantly men 60.7%). 45% belonged to the most deprived population quintile in the UK. Median BMI was 27.6 (IQR 23.9-32.4) kg/m2. The primary outcome (7-day mortality) occurred in 24%, increasing to 33% by day 30. Approximately one in ten patients required insulin infusion (9.8%). In univariate analyses, patients with type 2 diabetes had a higher risk of 7-day mortality [p &lt; 0.05, OR 2.52 (1.06, 5.98)]. Patients requiring insulin infusion had a lower risk of death [p = 0.02, OR 0.5 (0.28, 0.9)]. CKD in younger patients (&lt;70 years) had a greater risk of death [OR 2.74 (1.31-5.76)]. BMI, microvascular and macrovascular complications, HbA1c, and random non-fasting blood glucose on admission were not associated with mortality. On multivariate analysis, CRP and age remained associated with the primary outcome [OR 3.44 (2.17, 5.44)] allowing for a validated predictive model for death by day 7.ConclusionsHigher CRP and advanced age were associated with and predictive of death by day 7. However, BMI, presence of diabetes complications, and glycaemic control were not. A high proportion of these patients required insulin infusion warranting increased input from the inpatient diabetes teams.

Heterogeneity of abdominal obesity in patients with cardiovascular diseases

Aim: To assess the content of visceral adipose tissue (VAT) in patients with abdominal obesity and its relationship with metabolic disorders.Material and methods. Patients with abdominal obesity (n=107) were included in the study. All participants had an assessment of anthropometric parameters (height, weight), calculation of body mass index (BMI), proportion of total adipose tissue and VAT (bioimpedance analyzer), high-density lipoprotein cholesterol (HDL-c) levels, triglycerides, fasting blood glucose, epicardial thickness adipose tissue (two-dimensional echocardiography).Results. The median share of VAT (bioimpedance method) was 13%. Patients with abdominal obesity are divided by VAT into 2 groups: ≥14% or ≤13%. Patients with VAT≥14% had significantly higher levels of triglycerides (1.76 [1.27; 2.38] mmol / L) and glucose (6.33 [5.78; 7.87] mmol / L), and below HDL-c levels (0.95 [0.85; 1.21] mmol / L) compared with patients with VAT≤13% (1.32 [1.02; 1.50], 5.59 [5, 11; 6.16] and 1.31 [1.07; 1.58] mmol / L, respectively; p<0.001 for all three comparisons). A significant correlation was found between VAT and triglyceride, glucose and HDL-c levels (r=0.40; r=0.40; r=-0.31, respectively; p<0.001).Conclusion. Persons with abdominal obesity are heterogeneous in the proportion of VAT. The proportion of VAT above the median is associated with metabolic disorders that are significant for the development and progression of atherosclerosis. An increase in BMI in obese individuals is not associated with an increase in VAT and an increase in the severity of metabolic disorders.

A propolis-derived small molecule ameliorates metabolic syndrome in obese mice by targeting the CREB/CRTC2 transcriptional complex

The molecular targets and mechanisms of propolis ameliorating metabolic syndrome are not fully understood. Here, we report that Brazilian green propolis reduces fasting blood glucose levels in obese mice by disrupting the formation of CREB/CRTC2 transcriptional complex, a key regulator of hepatic gluconeogenesis. Using a mammalian two-hybrid system based on CREB-CRTC2, we identify artepillin C (APC) from propolis as an inhibitor of CREB-CRTC2 interaction. Without apparent toxicity, APC protects mice from high fat diet-induced obesity, decreases fasting glucose levels, enhances insulin sensitivity and reduces lipid levels in the serum and liver by suppressing CREB/CRTC2-mediated both gluconeogenic and SREBP transcriptions. To develop more potential drugs from APC, we designed and found a novel compound, A57 that exhibits higher inhibitory activity on CREB-CRTC2 association and better capability of improving insulin sensitivity in obese animals, as compared with APC. In this work, our results indicate that CREB/CRTC2 is a suitable target for developing anti-metabolic syndrome drugs.

Diabetes Resolution at 10 Years After Biliopancreatic Diversion in Overweight and Class 1 Obese Patients with Type 2 Diabetes

Background Long-term anti-diabetic effects of BPD in overweight or class 1 obese T2DM patients were investigated reporting the results at 10 years after BPD performed in severely non-obese T2DM patients. Material and Methods Thirty T2DM patients with BMI lower than 35 kg/m2 were investigated at 1, 5, and 10 years after BPD, and the results are compared with those of 30 T2DM patients followed for 10 years on pharmacological and/or behavioral conventional therapy. Results Mean levels of fasting blood glucose (FBG) and serum glycated hemoglobin (HbA1C) showed a marked reduction 1 year after BPD, values remaining slightly above the diabetic range throughout the entire follow-up. T2DM remission was observed in about 50% of the cases at 5 and 10 years after the operation. In 16 patients (53%), severe BPD-related complications developed, in ten cases requiring a surgical revision of the operation. In the BPD group, one patient died for malignant lymphoma and two patients after surgical revision. Within the control group, during the 10-year follow-up, no changes in the diabetic status were observed, being the FBG and HbA1C mean values higher than those recorded in the BPD patients at any follow-up time. All T2DM subjects of the control group were alive at the end of the 10-year follow-up. Conclusion Despite satisfactory long-term metabolic outcomes, these data indicate that BPD should be used with caution as a metabolic procedure in the treatment of T2DM in overweight or class 1obese patients. Graphical abstract

Grainyhead 1 acts as a drug-inducible conserved transcriptional regulator linked to insulin signaling and lifespan

Aging is impacted by interventions across species, often converging on metabolic pathways. Transcription factors regulate longevity yet approaches for their pharmacological modulation to exert geroprotection remain sparse. We show that increased expression of the transcription factor Grainyhead 1 (GRH-1) promotes lifespan and pathogen resistance in Caenorhabditis elegans. A compound screen identifies FDA-approved drugs able to activate human GRHL1 and promote nematodal GRH-1-dependent longevity. GRHL1 activity is regulated by post-translational lysine methylation and the phosphoinositide (PI) 3-kinase C2A. Consistently, nematodal longevity following impairment of the PI 3-kinase or insulin/IGF-1 receptor requires grh-1. In BXD mice, Grhl1 expression is positively correlated with lifespan and insulin sensitivity. In humans, GRHL1 expression positively correlates with insulin receptor signaling and also with lifespan. Fasting blood glucose levels, including in individuals with type 2 diabetes, are negatively correlated with GRHL1 expression. Thereby, GRH-1/GRHL1 is identified as a pharmacologically malleable transcription factor impacting insulin signaling and lifespan.