Indices Of Glucose Metabolism Research Articles

Astragaloside IV inhibits protein tyrosine phosphatase 1B and improves insulin resistance in insulin-resistant HepG2 cells and triglyceride accumulation in oleic acid (OA)-treated HepG2 cells

Ethnopharmacological relevanceAstragaloside IV (AST IV) is the active component of Astragalus membranaceus (Fisch.) Bunge, which regulates lipid and carbohydrate metabolism and improves insulin resistance. In this study, we investigated the effects of AST IV on insulin resistant cells and a non-alcoholic fatty liver disease (NAFLD) model induced by high-concentration insulin or oleic acid (OA) in HepG2 cells, as well as the associated regulatory markers. MethodsFirst, the target of AST IV was predicted via pharmacophore model matching and molecular docking. Then, enzyme kinetics experiments were conducted in vitro to determine the effect of AST IV on the target protein. Next, AST IV's toxicity was tested on HepG2 cells in vitro, through an insulin resistance model and an NAFLD model, by high-concentration insulin or OA, respectively. To explore the effects of AST IV on insulin resistance and lipid metabolism, we detected the related indexes of glucose and lipid metabolism through commercially available kits. Relevant proteins were also detected by Western blot to provide future direction for study. ResultsOur preliminary results of pharmacophore model matching and molecular docking suggested that AST IV and protein tyrosine phosphatase 1B (PTP1B) can be well-combined through hydrogen bonding. Further, the enzyme kinetics experiment showed that AST IV was an effective and specific inhibitor to PTP1B. We found that the protein level of PTP1B in HepG2 cells was significantly increased after treating with high-concentration insulin or OA. Additionally, the intervention of AST IV significantly increased glucose consumption in an insulin resistance model and reduced the content of triglyceride (TG), total cholesterol (TC), and free fatty acid (FFA) in the NAFLD model. Moreover, the 2-N-(7-nitrobenze-2-oxa-1, 3 diazol-4-yl) (2-NBDG) uptake rate in the NAFLD model was also greatly improved. These results validated the effects of AST IV on improving insulin resistance and lipid accumulation. Furthermore, Western blot results illustrated that AST IV suppressed PTP1B and increased levels of phosphorylated insulin receptor (p-IR) and phosphorylated insulin receptor substrate-1 (p-IRS-1) in insulin-resistant HepG2 cells, while also decreasing protein levels of PTP1B and sterol element regulatory binding protein-1c (SREBP-1c) in the NAFLD model. ConclusionThis study demonstrated that AST IV inhibited PTP1B and effectively improved insulin resistance in insulin-resistant HepG2 cells and triglyceride accumulation in OA-treated HepG2 cells.

18F-Fluorodeoxyglucose Positron Emission Tomography Tracks the Heterogeneous Brain Susceptibility to the Hyperglycemia-Related Redox Stress.

In cognitively normal patients, mild hyperglycemia selectively decreases 18F-Fluorodeoxyglucose (FDG) uptake in the posterior brain, reproducing Alzheimer disease pattern, hampering the diagnostic accuracy of this widely used tool. This phenomenon might involve either a heterogeneous response of glucose metabolism or a different sensitivity to hyperglycemia-related redox stress. Indeed, previous studies reported a close link between FDG uptake and activation of a specific pentose phosphate pathway (PPP), triggered by hexose-6P-dehydrogenase (H6PD) and contributing to fuel NADPH-dependent antioxidant responses in the endoplasmic reticulum (ER). To clarify this issue, dynamic positron emission tomography was performed in 40 BALB/c mice four weeks after administration of saline (n = 17) or 150 mg/kg streptozotocin (n = 23, STZ). Imaging data were compared with biochemical and histological indexes of glucose metabolism and redox balance. Cortical FDG uptake was homogeneous in controls, while it was selectively decreased in the posterior brain of STZ mice. This difference was independent of the activity of enzymes regulating glycolysis and cytosolic PPP, while it was paralleled by a decreased H6PD catalytic function and enhanced indexes of oxidative damage. Thus, the relative decrease in FDG uptake of the posterior brain reflects a lower activation of ER-PPP in response to hyperglycemia-related redox stress in these areas.

Pharmacological Management of Glucose Dysregulation in Patients Treated with Second-Generation Antipsychotics.

Fasting hyperglycemia, impaired glucose tolerance, prediabetes, and diabetes are frequently present in patients treated with second-generation antipsychotics (SGAPs) for schizophrenia, bipolar disorder, and other severe mental illnesses. These drugs are known to produce weight gain, which may lead to insulin resistance, glucose intolerance, and metabolic syndrome, which constitute important risk factors for the emergence of diabetes. The aim of this review was to formulate therapeutic guidelines for the management of diabetes in patients treated with SGAPs, based on the association between SGAP-induced weight gain and glucose dysregulation. A systematic search in PubMed from inception to March 2020 for randomized controlled trials (RCTs) of diabetes or prediabetes in patients treated with SGAPs was performed. PubMed was also searched for the most recent clinical practice guidelines of interventions for co-morbid conditions associated with diabetes mellitus (DM) (arterial hypertension and dyslipidemia), lifestyle interventions and switching from high metabolic liability SGAPs to safer SGAPs. The search identified 14 RCTs in patients treated with SGAPs. Drug therapy using metformin as first-line therapy and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or perhaps sodium-glucose cotransporter-2 (SGLT2) inhibitors as add-on therapy, might be preferred in these patients as well, as they favorably influence glucose metabolism and body mass index, and provide cardio-renal benefits in general to the DM population, although for the SGLT-2 inhibitors there are no RCTs in this specific patient category so far. Metformin is also useful for treatment of prediabetes. Arterial hypertension should be treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and statins should be used for correction of dyslipidemia. The outcome of lifestyle-changing interventions has been disappointing. Switching from clozapine, olanzapine, or quetiapine to lower cardiometabolic-risk SGAPs, like aripiprazole, brexpiprazole, cariprazine, lurasidone, or ziprasidone, has been recommended.

Association between Thyroid Function and Nonalcoholic Fatty Liver Disease in Euthyroid Type 2 Diabetes Patients.

Thyroid function and type 2 diabetes mellitus (T2DM) are both associated with increased risks of adverse clinical outcomes in nonalcoholic fatty liver disease (NAFLD). Our study is aimed at evaluating the association between thyroid function and NAFLD in T2DM patients with normal thyroid function (euthyroid) and analyzing the potential effects of metformin on the pathological process. Overall, 369 T2DM patients were enrolled between July 2017 and September 2018 and stratified into NAFLD and non-NAFLD groups. Data on age, gender, body mass index (BMI, kg/m2), metformin use, and basal metabolic rate (BMR) were obtained from participants' records. All patients were tested for biochemical markers, indexes of glucose metabolism, lipid metabolism, bone metabolism, and thyroid function at baseline. Multivariate analyses detected increased odds of NAFLD among individuals with T2DM per unit increase in their BMI and free triiodothyronine (FT3) and thyroid stimulating hormone (TSH); the odds ratios (OR) were 1.25, 3.02, and 1.58, respectively (all p < 0.05). Positive correlations were detected between alanine aminotransferase (ALT) and FT3 (r = 0.221, p = 0.010), and negative correlations were noted between TSH and BMR (r = −0.618, p < 0.001) and between BMR and FT3 (r = −0.452, p < 0.001) in T2DM subjects with NAFLD. A significant difference in serum FT3 (t = 2.468, p = 0.0167) and TSH (t = 2.658, p = 0.010) levels was found between obese individuals with NAFLD who used and did not use metformin. The pathological mechanism of T2DM complicated by NAFLD in euthyroid patients may be associated with insulin resistance and a thyroid hormone resistance-like manifestation, i.e., relevant hypothyroidism. Metformin can potentially decrease the double-resistance situation, especially in obese individuals.

Association Between Atherogenic Index of Plasma, Blood Pressure and Impaired Glucose Metabolism; Results of Diabetes Screening in a Tertiary Healthcare Center

Association Between Atherogenic Index of Plasma, Blood Pressure and Impaired Glucose Metabolism; Results of Diabetes Screening in a Tertiary Healthcare Center

Study on the levels of 25(OH)D, inflammation markers and glucose and fat metabolism indexes in pregnant women of Han nationality in Jiangsu province with gestational diabetes mellitus.

The aim of this study is to investigate the levels of 25(OH)D, inflammation markers and glucose and fat metabolism indexes in pregnant women with Gestational diabetes mellitus (GDM).One hundred and ten cases GDM and 100 cases healthy pregnant women in the First People's Hospital of Lianyungang City from October 2016 to December 2018 were recruited for this observational cross-sectional study. Each participant's anthropometric and demographic data was recorded. Blood samples were collected and analyzed to determine the levels of 25(OH)D, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), fasting blood glucose, fasting blood insulin, hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol and triglycerides.Inflammatory markers and glucose and fat metabolism indexes were all significantly higher in the GDM group than that in the control group, while Serum 25(OH)D level in the GDM group was significantly lower. Serum 25(OH)D levels were negatively correlated with hs-CRP, while not with TNF-α. Furthermore, Serum 25(OH)D, hs-CRP and TNF-α levels were all associated with increased risk of developing GDM.Nowadays, the reports on the association between 25(OH)D level and GDM were controversial. Our results are consistent with the view that there was association between 25(OH)D level and GDM, and expand the literature by showing the roles of 25(OH)D, inflammation markers as well as glucose and fat metabolism indexes in the risk of developing GDM in the pregnant women with the low overall levels of 25(OH)D before delivery. This broadens our knowledge on the pathophysiology of GDM, which may be helpful in prevention and treatment of GDM.

Protective effect of probiotics in patients with non-alcoholic fatty liver disease.

To investigate the effects of probiotics on liver function, glucose and lipids metabolism, and hepatic fatty deposition in patients with non-alcoholic fatty liver disease (NAFLD).Totally 140 NAFLD cases diagnosed in our hospital from March 2017 to March 2019 were randomly divided into the observation group and control group, 70 cases in each. The control group received the diet and exercise therapy, while the observation group received oral probiotics based on the control group, and the intervention in 2 groups lasted for 3 months. The indexes of liver function, glucose and lipids metabolism, NAFLD activity score (NAS), and conditions of fecal flora in 2 groups were compared before and after the treatment.Before the treatment, there were no significant differences on alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamine transferase (GGT), total bilirubin (TBIL), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR), NAFLD activity score (NAS), and conditions of fecal flora in 2 groups (P > .05). After the treatment, ALT, AST, GGT, TC, TG, HOMA-IR, NAS, and conditions of fecal flora in the observation group were better than those in the control group, and the observation group was better after treatment than before. All these above differences were statistically significant (P < .05).Probiotics can improve some liver functions, glucose and lipids metabolism, hepatic fatty deposition in patients with NAFLD, which will enhance the therapeutic effects of NAFLD.

Cranberry Polyphenolic Extract Exhibits an Antiobesity Effect on High-Fat Diet–Fed Mice through Increased Thermogenesis

Although polyphenol-rich cranberry extracts reportedly have an antiobesity effect, the exact reason for this remains unclear. In light of the reported health benefits of the polyphenolic compounds in cranberry, we investigated the effects and mechanism of a cranberry polyphenolic extract (CPE) in high-fat diet (HFD)-fed obese mice. The distributions of individual CPE compounds were characterized by HPLC fingerprinting. Male C57BL/6J mice (4 wk old) were fed for 16 wk normal diet (ND, 10% fat energy) or HFD (60% fat energy) with or without 0.75% CPE in drinking water (HFD+CPE). Body and adipose depot weights, indices of glucose metabolism, energy expenditure (EE), and expression of genes related to brown adipose tissue (BAT) thermogenesis, and inguinal/epididymal white adipose tissue (iWAT/eWAT) browning were measured. After 16 wk, the body weight was 22.5% lower in the CPE-treated mice than in the HFD group but remained 17.9% higher than in the ND group. CPE treatment significantly increased EE compared with that of the ND and HFD groups. The elevated EE was linked with BAT thermogenesis, and iWAT/eWAT browning, shown by the induction of thermogenic genes, especially uncoupling protein 1 (Ucp1), and browning-related genes, including Cd137, a member of the tumor necrosis factor receptor superfamily (Tnfrsf9). The mRNA expression and abundance of uncoupling protein 1 in BAT of CPE-fed mice were 5.78 and 1.47 times higher than in the HFD group, and 0.61 and 1.12 times higher than in the ND group, respectively. Cd137 gene expression in iWAT and eWAT of CPE-fed mice were 2.35 and 3.13 times higher than in the HFD group, and 0.84 and 1.39 times higher than in the ND group, respectively. Dietary CPE reduced but did not normalize HFD-induced body weight gain in male C57BL/6J mice, possibly by affecting energy metabolism.

Construction of transmembrane 6 superfamily member 2 E167K gene knock-in mouse model by using CRISPR/Cas9 technology

Objective: To construct a transmembrane 6 superfamily member 2 (Tm6sf2) E167K gene knock-in mouse model. Methods: The plasmid was constructed to simultaneously express the single-stranded guide RNA Cas9 at a specific site of the mouse Tm6sf2 gene in the donor plasmid carrying the Tm6sf2 E167K fragment. The above two plasmids were injected into the mouse fertilized eggs together. The positive F0 generation mice were validated by PCR detection and sequencing. The number of F2 generation surviving mice in three genotypes of wild (Wt), heterozygous and knock-in (KI) were calculated. Wt and KI male mice (8 mice/ group) of F2 generation littermates were selected and given a normal diet for 8 weeks. The body weight of the mice was recorded every week, and the glucose metabolism and lipid metabolism indexes of the two mice were detected. The comparison between groups was performed with an independent sample t-test. Results: Genotype detection and sequencing results showed that the Tm6sf2 E167K gene knock-in mouse model was successfully established. KI mice had absence of homozygous lethal embryo phenotype. The body weight of KI mice was higher than that of Wt mice during lactation, and the difference between the two groups was statistically significant (P < 0.05).The fasting blood glucose of KI mice (9.50 ± 0.33)mmol/L was higher than that of Wt mice (7.80 ± 0.30)mmol/L, and the difference between the two groups was statistically significant (P < 0.05). During the oral glucose tolerance test, the 2-hour blood glucose level of KI mice (9.20 ± 0.51)mmol/L was higher than that of Wt mice (7.60 ± 0.18)mmol/L, and the difference between the two groups was statistically significant (P < 0.05). The liver triglyceride content of KI mice (8.40 ± 0.55)mg/g was higher than that of Wt mice (7.30 ± 0.63)mg/g, but the difference was not statistically significant (P > 0.05). There was no significant difference in plasma triglyceride levels between the two mice (P > 0.05). The Oil red O staining results showed that KI mice had more lipid accumulation in the centrilobular region of ​​liver than Wt mice. Conclusion: Tm6sf2 E167K gene knock-in mice were successfully constructed. Tm6sf2 E167K gene knock-in can cause abnormal glucose metabolism in mice and promote the occurrence of hepatic steatosis.

Lipocalin-2 counteracts metabolic dysregulation in obesity and diabetes.

Regulation of food intake is a recently identified endocrine function of bone that is mediated by Lipocalin-2 (LCN2). Osteoblast-secreted LCN2 suppresses appetite and decreases fat mass while improving glucose metabolism. We now show that serum LCN2 levels correlate with insulin levels and β-cell function, indices of healthy glucose metabolism, in obese mice and obese, prediabetic women. However, LCN2 serum levels also correlate with body mass index and insulin resistance in the same individuals and are increased in obese mice. To dissect this apparent discrepancy, we modulated LCN2 levels in mice. Silencing Lcn2 expression worsens metabolic dysfunction in genetic and diet-induced obese mice. Conversely, increasing circulating LCN2 levels improves metabolic parameters and promotes β-cell function in mouse models of β-cell failure acting as a growth factor necessary for β-cell adaptation to higher metabolic load. These results indicate that LCN2 up-regulation is a protective mechanism to counteract obesity-induced glucose intolerance by decreasing food intake and promoting adaptive β-cell proliferation.

1530-P: Metabolic Characteristics in Chinese Sarcopenia Patients with Type 2 Diabetes

Objective: To evaluate glucose metabolism characteristics in middle-aged and elderly sarcopenia patients with type 2 diabetes. Methods: Data were collected from a multicenter, cross-sectional survey study. Eligible patients aged 50 years or older with a previous diagnosis of type 2 diabetes were recruited from the endocrinology department of nine different hospitals in Beijing, China. All participants were grouped into a probable sarcopenia group with low muscle strength and a nonsarcopenia group with normal muscle strength according to the recommendations from EWGSOP2 (2018). Body composition, glucose metabolism, laboratory and nutritional index were compared between two groups. Results: A total of 1125 diabetic participants were included, with 405 in probable sarcopenia group and 720 in nonsarcopenia control group. Compared to the controls, the probable sarcopenia participants were older and had lower waist-to-hip ratio and BMI, higher fasting plasma glucose level and glycosylated hemoglobin (HbA1c), decreased estimated glomerular filtration rate, and lower bone mineral content, basal metabolic rate, fatless upper arm circumference, appendicular skeletal muscle mass index (ASMI) and muscle quality in both men and women. The prevalence of low muscle mass was obviously elevated in probable sarcopenia group in both sexes (men: 11.0% vs. 25.4%, women: 6.8% vs. 19.1%). Multivariable logistic regression analysis showed that aged, male sex, low BMI, increased HbA1c, diabetic nephropathy and decreased serum albumin level were risk factors associated with low muscle strength in diabetes patients. Conclusions: Sarcopenic diabetic patients were older and had lower BMI, worse nutritional status and glucose metabolism, decreased renal function and reduced muscle quality and mass with a greater likelihood of osteoporosis. Clinically, diabetic aged patients should receive an assessment on muscle strength and muscle quality to optimize their treatment program. Disclosure Q. He: None. L. Guo: None.

Cardiometabolic Benefits of a Weight-Loss Mediterranean Diet/Lifestyle Intervention in Patients with Obstructive Sleep Apnea: The "MIMOSA" Randomized Clinical Trial.

Although continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea (OSA), its cardiometabolic benefits are questionable. Our aim was to explore whether the combination of a weight-loss Mediterranean diet/lifestyle intervention with OSA standard care leads to greater cardiometabolic improvements compared with standard care alone. We randomly assigned 187 adult, overweight, polysomnography-diagnosed moderate-to-severe OSA patients to a standard care group (SCG, n = 65), a Mediterranean diet group (MDG, n = 62) or a Mediterranean lifestyle group (MLG, n = 60). All three groups were prescribed with CPAP. Additionally, the SCG only received brief written healthy lifestyle advice, while intervention arms were subjected to a six-month weight-loss behavioral intervention based on the Mediterranean diet. The MLG also received guidance for improving physical activity and sleep habits. Glucose metabolism indices, blood lipids, liver enzymes and blood pressure improved only in intervention arms, and were significantly lower compared to the SCG post-intervention (all p < 0.05). The age-, sex-, baseline- and CPAP use-adjusted relative risk (95% confidence interval) of metabolic syndrome was 0.58 (0.34–0.99) for the MDG and 0.30 (0.17–0.52) for the MLG compared to the SCG. The MLG additionally presented a lower relative risk of metabolic syndrome compared to the MDG (0.52 (0.30–0.89)). After further adjustment for body-weight change, a lower relative risk of metabolic syndrome was still evident for the MLG compared to the SCG. In conclusion, although standard care alone does not improve OSA patients’ cardiometabolic profile, its combination with a weight-loss Mediterranean diet/lifestyle intervention leads to significant cardiometabolic benefits.

Associations between circulating bone-derived hormones osteocalcin, lipocalin 2, and glucose metabolism in patients with acromegaly

Objective The aim of this study was to examine the change of serum bone-derived hormones osteocalcin and lipocalin 2 (LCN2) level in patients with active acromegaly, and to further investigate the potential role of osteocalcin and LCN2 in glucose metabolism. Methods Fifty consecutive patients diagnosed as acromegaly in Nanjing Drum Tower Hospital from December 2016 to August 2018 were recruited. Of those, 41 patients after operations with complete follow-up data were also included. 30 sex, age, and body mass index matched healthy persons as normal controls. Serum osteocalcin and LCN2 levels were compared between controls and patients with acromegaly, as well as at pre- and post- operation periods. Univariate and multivariate linear regression analyses were used to investigate the correlation between bone-derived hormones and glucose metabolism indexes and to determine the independent associations between variables. Results Compared with normal controls, serum osteocalcin increased [(55.45±34.02 vs 19.46±6.69)ng/ml, P 0.05). After operation, with the decrease of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1), serum osteocalcin level decreased [24.79(18.39, 32.59) vs 43.51(26.73, 65.66)ng/ml, P<0.01] and LCN2 level increased [(45.15±15.33 vs 37.03±9.73)ng/ml, P<0.05] significantly compare to pre-operation levels. In a multivariate linear stepwise regression analysis, lean mass was shown to be the only positive predictor for LCN2 (β=0.44, P=0.015) and elevated serum IGF-1 was a positive predictor for osteocalcin (β=0.512, P<0.01). In the multivariate models, low LCN2 (β=-0.398, P=0.017) and elevated serum osteocalcin (β=0.553, P=0.001) were predictors for AUCINS, osteocalcin was a positive predictor of HOMA- β (β=0.519, P=0.004). GH (β=0.294, P=0.029) and IGF-1(β = 0.428, P=0.002) were all identified as positive predictors of HOMA-IR during multivariate testing in acromegaly patients. Conclusions Acromegaly patients had increased osteocalcin and decreased LCN2 serum levels, and corresponding alteration was detected with the correction of biochemical abnormalities. Serum osteocalcin and LCN2 were predictors of β-cell function in acromegaly patients. This study adds new evidence for the role of bone in regulating glucose metabolism in acromegaly. Key words: Acromegaly; Osteocalcin; Lipocalin 2; Glucose metabolism

Study on insulin resistance, glycolipid metabolism, and sex hormones in patients with polycystic ovary syndrome

Objective To evaluate the insulin resistance of patients with polycystic ovary syndrome (PCOS) by hyperinsulin-euglycemic clamp test, and to explore the characteristics of glycolipid metabolism and sex hormone levels in PCOS patients with insulin resistance. Methods Seventy-three patients with PCOS and 27 healthy women with body mass index and age matched with PCOS patients who were admitted to the Department of Endocrinology of Affiliated Hospital of Zunyi Medical University from July 2017 to February 2019 were underwent hyperinsulin-euglycemic clamp test. All subjects were grouped according to glucose metabolic rate, body mass index, and homeostasis model assessment for insulin resistance (HOMA-IR), the changes and differences of glucose and lipid metabolism and sex hormone indexes in PCOS patients were analyzed. Results In the PCOS group, impaired glucose regulation accounted for 3.23% (1/31), and abnormal lipid metabolism for 9.68% (3/31). In the PCOS with insulin resistance group, impaired glucose regulation accounted for 7.14% (3/42). Abnormal blood lipid metabolism reached 47.62% (20/42), and 5 patients were diagnosed with metabolic syndrome, accounting for 11.90%. Correlation analysis showed glucose metabolic rate and body mass index, waist-to-hip ratio, systolic blood pressure, fasting plasma glucose, fasting insulin, HOMA-IR, cortisol, triglyceride, total cholesterol, low density lipoprotein-cholesterol (LDL-C), free androgen index (FAI), and glutamyl transpeptidase (GGT) were negatively correlated(all P<0.05), while positively correlated with high density lipoprotein-cholesterol (HDL-C; P=0.028). HOMA-IR was positively correlated with body mass index, waist-to-hip ratio, systolic blood pressure, fasting plasma glucose, fasting insulin, HbA1C, LDL-C (P<0.05), and negatively correlated with glucose metabolic rate and HDL-C (P<0.05). Body mass index and waist-to-hip ratio, systolic blood pressure, fasting plasma glucose, fasting insulin, HOMA-IR, triglyceride, and LDL-C (P<0.05) were positively correlated, and negatively correlated with glucose metabolic rate, HDL-C, and sex hormone binding globulin (SHBG; P<0.01). Multivariate linear stepwise regression analysis showed that body mass index, total cholesterol, triglyceride, and cortisol were principal factors affecting glucose metabolic rate. Fasting plasma glucose, fasting insulin, and systolic blood pressure were important factors influencing HOMA-IR. Glucose metabolic rate, HOMA-IR, HDL-C, while SHBG were still vital to body mass index. Conclusion FAI, SHBG, and cortisol may be involved in the insulin resistance development of PCOS patients, and PCOS patients with insulin resistance were more susceptible to metabolic disorders. Key words: Polycysic ovarian syndrome; Insulin resistance; Hyperinsulin-euglycemic clamp; Glycolipid metabolism; Sex hormone

Liver iron concentration is an independent risk factor for the prediabetic state in β-thalassemia patients

Beta-thalassemia major (β-TM) comprises a group of inherited blood disorders characterized by the reduced synthesis of β-globin chains. Iron overload following blood transfusion can affect major tissues involved in glucose metabolism, leading to different glucose metabolic disorders in these patients. The aim of the present study was to compare glucose metabolism and iron overload indices in β-TM patients with prediabetic and normoglycemic states. This analytical study was performed on 49 patients with β-TM (age > 18 years), receiving regular blood transfusions. The fasting plasma glucose (FPG) and glucose tolerance tests indicated 32 normoglycemic and 17 prediabetic cases. The serum levels of C-peptide, fructosamine, fasting serum insulin, and serum ferritin were measured. In addition, T2*-weighted magnetic resonance imaging (MRI) of the heart and liver was carried out. Glycemic metabolism indices, including quantitative insulin sensitivity check index (QUICKI) and homeostatic model assessment for insulin resistance (HOMA-IR), were also calculated. The HOMA-IR score was significantly higher, while the QUICKI score was significantly lower in prediabetic patients, compared to normoglycemic patients (median [IR], 2.59 [2.19] vs. 1.46 [1.03], p = 0.007; mean ± SD, 0.34 ± 0.03 vs. 0.37 ± 0.04, p = 0.01). On the other hand, β-cell function was not significantly different between the groups. The liver iron concentration (LIC) at a cutoff point of 5.82 mg/g dry weight showed 93% sensitivity and 70% specificity for differentiation of prediabetic and normoglycemic states (AUC, 0.81 [95% CI, 0.65–0.95]; p = 0.002). Based on the findings, HOMA-IR and QUICKI can be applied as useful glycemic metabolism indices for predicting prediabetic and normoglycemic states among β-TM patients. Also, LIC was an independent risk factor for the prediabetic state.

Associations of impaired glucose metabolism with chronic peridontitis in pre-diabetes patients

Objective To investigate the associations of impaired glucose metabolism and insulin resistance with chronic periodontitis in pre-diabetes patients. Methods A cross-sectional analysis was conducted and we included a total of 171 pre-diabetes patients aged 30-65 years, free of diabetes. pre-diabetes was defined as impaired fasting glucose (IFG) [fasting glucose (FG): 6.1-7.0 mmol/L] and/or impaired glucose tolerance (IGT) [oral glucose tolerance test (OGTT): 7.8-11.0 mmol/L]. Chronic periodontitis was defined according to Centers for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) definition and the patients were divided into mild, moderate, and severe chronic periodontitis groups [mild: at least two interproximal sites with clinical attachment loss (CAL) ≥3 mm and at least two interproxima sites with probing depth (PD) ≥4 mm or 1 site with PD≥5 mm; moderate: at least two interproximal sites with CAL ≥4 mm and at least two interproxima sites with at least two interproximal sites with PD ≥5 mm; severe: at least two interproximal sites with CAL ≥6 mm and at least one interproxima site with at least two interproximal sites with PD≥5 mm]. A periodontal examination indexes [plaque index (PLI), PD, CAL, and bleeding on probing (BOP)] and glucose metabolism indexes [FG, OGTT, hemoglobinA1c (HbA1c), fasting insulin and homeostasis model assessments of insulin resistance (HOMA-IR)] were measured. The association of glucose metabolism and chronic periodontitis was investigated by multivariable logistic regression analysis. Results FG in the moderate and severe chronic periodontitis groups was significantly higher compared with mild chronic periodontitis group, HOMA-IR in the moderate and severe chronic periodontitis groups was significantly higher compared with mild chronic periodontitis group, OGTT in the severe chronic periodntitis group was significantly higher compared with mild chronic peridontitis group and moderate chronic periodontitis groups, and there was no significant difference between moderate and mild chronic periodontitis groups. For the insulin and HbA1c, there was no significant difference among mild, moderate and severe chronic periodontitis groups. After multivariable adjustment of age, gender, smoking status, hypertension and body mass index, IFG (OR=1.39, 95%CI: 1.01-1.98) and HOMA-IR (OR=1.36, 95%CI: 1.04-1.76) were associated with moderate periodontitis; IFG (OR=1.64, 95%CI: 1.17-2.40), IGT (OR=1.65, 95%CI: 1.21-2.26), and HOMA-IR (OR=1.72, 95%CI: 1.23-2.41) were significantly associated with severe periodontitis. Conclusion Our data provided evidences that impaired glucose metabolism were associated with chronic periodontitis among pre-diabetes patients.

Transendothelial Insulin Transport is Impaired in Skeletal Muscle Capillaries of Obese Male Mice.

The continuous endothelium of skeletal muscle (SkM) capillaries regulates insulin's access to skeletal myocytes. Whether impaired transendothelial insulin transport (EIT) contributes to SkM insulin resistance (IR), however, is unknown. Male and female C57/Bl6 mice were fed either chow or a high-fat diet for 16 weeks. Intravital microscopy was used to measure EIT in SkM capillaries, electron microscopy to assess endothelial ultrastructure, and glucose tracers to measure indices of glucose metabolism. Diet-induced obesity (DIO) male mice were found to have a ~15% reduction in EIT compared with lean mice. Impaired EIT was associated with a 45% reduction in endothelial vesicles. Despite impaired EIT, hyperinsulinemia sustained delivery of insulin to the interstitial space in DIO male mice. Even with sustained interstitial insulin delivery, DIO male mice still showed SkM IR indicating severe myocellular IR in this model. Interestingly, there was no difference in EIT, endothelial ultrastructure, or SkM insulin sensitivity between lean female mice and female mice fed a high-fat diet. These results suggest that, in male mice, obesity results in ultrastructural alterations to the capillary endothelium that delay EIT. Nonetheless, the myocyte appears to exceed the endothelium as a contributor to SkM IR in DIO male mice.

Effect of obstructive sleep apnea syndrome on glycolipid metabolism and early atherosclerosis in diabetics

ObjectiveTo study the changes in glucose and lipid metabolism indexes and the condition of early atherosclerosis in patients with diabetes with and without obstructive sleep apnea syndrome (OSAS). MethodsPatients with type 2 diabetes mellitus (DM) aged 32–50 years who did not have significant complications were included. A total of 42 patients with DM with OSAS and 46 patients with DM without OSAS were chosen according to their sleep monitoring indexes. Height and weight were measured, and fasting blood glucose, postprandial blood glucose, endothelin (ET), nitric oxide (NO) and lipid profile were tested. Then, all the subjects were subjected to the pulse wave velocity (PWV) test. ResultsThe levels of glycated haemoglobin and triglycerides were significantly higher in patients with DM with OSAS than those in patients with DM without OSAS. ET, NO and PWV changed significantly. ConclusionPatients with diabetes with OSAS are more likely to have complications related to arteriosclerosis and aggravation of glycolipid metabolism disorder. Early intervention is recommended.

Effect of He Qi San on DNA Methylation in Type 2 Diabetes Mellitus Patients with Phlegm-blood Stasis Syndrome

AbstractThis study was performed to elucidate the potential influence of He Qi San (HQS) on glucose and lipid metabolism in type 2 diabetes mellitus (T2DM) patients with phlegm-blood stasis syndrome (PBSS), and to determine DNA methylation changes. Sixty T2DM patients with PBSS were randomly divided into control and HQS groups. The control group received conventional treatments, and the HQS group received conventional treatments plus HQS. Glucose metabolism (FPG, 2hPG, FINS, and HbA1c) and lipid metabolism indexes (TG, TC and LDL-C) were determined. Genes with differential DNA methylation were subjected to GO and KEGG analyses. Glucose and lipid metabolism indexes in both groups were reduced, but were much more pronounced in the HQS group. Differential promoter CpG methylation regions were identified in 682 genes, including 426 genes with high-CpG promoters, 150 genes with intermediate CpG promoters, and 106 genes with low CpG promoters. Genes with differential DNA methylation were mainly enriched in the AMPK and insulin signaling pathways, terpenoid backbone biosynthesis, and renin secretion. We concluded that HQS remarkably improved indexes of glucose and lipid metabolism in T2DM patients with PBSS through regulating the DNA methylation of genes in the AMPK and insulin signaling pathways and terpenoid backbone biosynthesis.

Early development of decreased β‐cell insulin secretion in children and adolescents with hemoglobin H disease and its relationship with levels of anemia

Diabetes mellitus (DM) associated with iron overload has been reported among adults with transfusion-dependent thalassemia and those with non-transfusion-dependent thalassemia (NTDT), especially in β-thalassemia disease. However, little is known about glucose metabolism and how early its dysregulation can develop in α-thalassemia hemoglobin H (Hb H) disease, which is one of the most common types of NTDT worldwide. We prospectively calculated glucose metabolism index in 40 patients (aged 10-25 years) with Hb H disease. Glucose metabolism data were compared between patients with deletional versus nondeletional Hb H, and between patients with normal versus abnormal insulin secretion/sensitivity. Despite normal glucose tolerance in all patients, 52.5% had abnormal insulinogenic index indicating decreased β-cell insulin secretion. Patients with functional hemoglobin < 8 g/dL had significantly higher percentages of abnormal insulinogenic index. There was no significant difference in abnormal insulinogenic index between deletional and nondeletional Hb H. Decreased β-cell insulin secretion is highly prevalent among children and adolescents with Hb H disease, and it is associated with levels of functional anemia at baseline, but not with the type of Hb H disease. This result warrants heightened awareness among hematologists due to potentially increased risk of DM later in life.