The Changes of Lipidomic Profiles Reveal Therapeutic Effects of Exenatide in Patients With Type 2 Diabetes.

Objective: Exenatide has been demonstrated beneficial effects on patients with type 2 diabetes mellitus (T2DM) regarding lipid metabolism. However, the potential mechanism remains unclear. We used a lipidomic approach to evaluate lipid changes in response to treatment with exenatide in T2DM patients. Methods: Serum lipidomic profiles of 35 newly diagnosed T2DM patients (before and after exenatide treatment) and 20 age-matched healthy controls were analyzed by ultrahigh-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry. Results: A total of 45 lipid species including sphingomyelins (SMs), ceramides (CERs), lysophosphatidylcholines (LPCs), phosphatidylethanolamines (PEs), lysophosphatidylethanolamines (LPEs) and phosphatidylcholines (PCs) were identified in all participants. Compared to the healthy controls, 13 lipid species [SM (d18:1/18:0, d18:1/18:1), Cer (d18:1/18:0, d18:1/16:0, d18:1/20:0, d18:1/24:1), LPC (15:0, 16:0, 17:0), PC (19:0/19:0), LPE (18:0) and PE (16:0/22:6, 18:0/22:6)] were markedly increased in the T2DM group, while PE (17:0/17:0) and PC (18:1/18:0) were decreased (P < 0.05). The serum SM (d18:1/18:0, d18:1/18:1), LPC (16:0), and LPE (18:0) were significantly decreased after exenatide treatment, which was accompanied by the amelioration of lipids and glycemic parameters (TC, LDL-C, ApoA-I, FCP and HbA1c) in T2DM patients. The chord diagrams showed distinct correlation patterns between lipid classes and subclasses among healthy controls, T2DM patients before and after exenatide treatment. Conclusion: Our results revealed that the therapeutic benefits of exenatide on T2DM might be involved in the improved lipid metabolism, especially SM, LPC, and LPE. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03297879.

Relation of kidney function and homocysteine in patients with hypothyroidism.

OBJECTIVE: It has been found that both serum homocysteine (Hcy) and serum creatinine levels were increased in hypothyroidism patients. The aim of this study was to investigate the correlation between serum Hcy and kidney function in patients with subclinical hypothyroidism or hypothyroidism. METHODS: A total of 448 subjects were enrolled and divided into three groups: hypothyroidism (n = 129), subclinical hypothyroidism (n = 141), and control group (n = 168). Anthropometric information, metabolic parameters, serum Hcy and creatinine levels, and estimated glomerular filtration rate (eGFR) were analyzed. RESULTS: Compared with healthy subjects, patients with subclinical hypothyroidism or hypothyroidism had significantly higher serum Hcy and creatinine levels and lower eGFR level (all P < 0.001). Serum Hcy was negatively correlated with eGFR in subclinical hypothyroidism patients (r = -0.220, P = 0.009), and in hypothyroidism patients (r = -0.422, P < 0.001). After adjusting for age, sex and BMI, eGFR was still significantly correlated with serum Hcy in subclinical hypothyroidism or hypothyroidism patients (both P < 0.05). Levothyroxine treatment resulted in significantly decreased Hcy and increased eGFR in hypothyroidism patients (both P < 0.001). The decrease in Hcy was correlated with the increased eGFR after treatment (P = 0.001). CONCLUSION: Serum Hcy was negatively correlated with eGFR in subclinical hypothyroidism or hypothyroidism patients. After levothyroxine treatment, a correlation was found between the decrease in serum Hcy and the increase in eGFR in hypothyroidism patients.

The Prevalence of Euthyroid Hypertriiodothyroninemia in Newly Diagnosed Multiple Myeloma and its Clinical Characteristics.

OBJECTIVE: To evaluate the prevalence of euthyroid hypertriiodothyroninemia and/or hyperthyroxinemia and its clinical characteristics in multiple myeloma (MM) patients. METHODS: Previously untreated, newly diagnosed patients with MM were enrolled at the Beijing Chao-yang Hospital between January 2016 and December 2019. Thyroid function and clinical characteristics were analyzed. RESULTS: A total of 105 patients were enrolled in this study. Thirteen (12.38%) patients exhibited euthyroid hypertriiodothyroninemia with strikingly elevated total triiodothyronine (TT3) levels (>8 ng/mL). Among these 13 patients, 12 patients were immunoglobulin (Ig) G type (92.31%), and 1 patient was light-chain κ type (7.69%). Compared with other patients with MM, patients with hypertriiodothyroninemia were more likely to be IgG type and had higher serum globulin and lower albumin levels and more advanced International Staging System stage (all P < .05). Among the 13 euthyroid hypertriiodothyroninemia patients, 8 patients have been followed up and checked for thyroid function. The TT3 levels in all 8 patients were normalized to the reference range after antimyeloma chemotherapy. CONCLUSION: About 12% of patients with MM had euthyroid hypertriiodothyroninemia. Their strikingly elevated TT3 was normalized after chemotherapy. Clinicians should be aware of the possibility of high TT3 levels in euthyroid patients with MM and the potential risk of MM in patients with strikingly elevated TT3.

The association between albuminuria and thyroid antibodies in newly diagnosed type 2 diabetes mellitus patients with Hashimoto's thyroiditis and euthyroidism.

BACKGROUND: Microalbuminuria is a prognostic marker of diabetes kidney disease. It is generally diagnosed as the ratio of urinary albumin to creatinine (UACR) of 30-300 mg/g. Hashimoto's thyroiditis is a common disease in the endocrinology and the thyroid antibodies may associated with kidney disease. We investigated the UACR in the newly diagnosed T2DM with Hashimoto's thyroiditis and tried to detect the relationship between the UACR and thyroid antibodies. METHODS: One hundred twenty newly diagnosed T2DM patients with Hashimoto's thyroiditis and euthyroidism and 50 sex and age-matched T2DM with non-Hashimoto's and other thyroid disease were recruited. T2DM patients were divided into 2 groups by the titer of TPOAb: (1). TPOAb (+) group: T2DM with positive TPOAb (n = 105); (2). TPOAb (-) group: T2DM with negative TPOAb (n = 65). RESULTS: T2DM with positive TPOAb group had higher UACR than T2DM with negative TPOAb group (21.55 ± 7.28 vs 15.13 ± 5.69 mg/g, P < 0.01). UACR were positively related to BMI (r = 0.255, P < 0.05), FPG (r = 0.285, P < 0.05), HbA1c (r = 0.260, P < 0.05) and TPOAb (r = 0.349, P < 0.05). HbA1c (ß = 0.793, P < 0.05), BMI (ß = 0.342, P < 0.05) and lnTPOAb (ß = 1.207, P < 0.05) were independently associated with UACR. CONCLUSIONS: In the newly diagnosed T2DM patients, Hashimoto's thyroiditis with TPOAb positive had higher UACR levels. TPOAb titer, BMI and HbA1c were independent associated with UACR in these patients.

The effect of exenatide on fasting bile acids in newly diagnosed type 2 diabetes mellitus patients, a pilot study.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrated good glycemic efficacy in patients with type 2 diabetes mellitus (T2DM) recent years, whereas studies on GLP-1 RAs' biliary effects were limited. Therefore, we aimed to assess the effect of exenatide on bile acids (BAs) and investigate the role of BAs in the glycemic control effect of exenatide. METHODS: Thirty-eight newly diagnosed T2DM participants without glucose-lowering drugs intake were recruited. Plasma total bile acids in fasting state (FTBAs) and other parameters were tested at baseline. Then exenatide were applied to the T2DM participants for 12 weeks. FTBAs and glycemic parameters were measured again after exenatide treatment, and correlation analysis between changes of FTBAs and glycemic parameters were conducted to investigate the role of BAs in the glycemic control effect of exenatide. RESULTS: The baseline FTBAs level of T2DM patients had no significance (3.84 ± 2.06 vs. 3.87 ± 2.89, P = 0.954) compared with healthy subjects. After 12-week exenatide treatment for the T2DM patients, FTBAs were decreased from 3.84 ± 2.06 µmol/L to 3.06 ± 1.27 µmol/L (P < 0.01). The correlation analysis showed that changes of FTBAs was positively correlated with changes of FPG (r = 0.355, P < 0.05). CONCLUSIONS: Our results demonstrated a decreased FTBAs level after exenatide treatment for 12 weeks, without the interference of metformin and other glucose-lowering drugs. The reduction of FTBAs might not exert a positive role in the glycemic control effect of exenatide. TRIAL REGISTRATION: Trial registration number: NCT04303819. Registered in March 11, 2020 - Retrospectively registered.

The Relationship Between the Impairment of Endothelial Function and Thyroid Antibodies in Hashimoto's Thyroiditis Patients with Euthyroidism.

Endothelial dysfunction is the important early step in the development of atherosclerosis. Hypothyroidism caused by Hashimoto's thyroiditis and other thyroid disease is one of the risk factors of endothelial dysfunction. The present study tried to investigate the endothelial function and its associated factors in Hashimoto thyroiditis with euthyroidism. A total of 95 newly diagnosed Hashimoto's thyroiditis patients with euthyroidism and 45 healthy controls were studied. Hashimoto's patients were divided into 3 subgroups namely, single thyroglobulin antibody (TGAb) positive subgroup, single thyroid peroxidase antibody (TPOAb) positive subgroup, and both TGAb and TPOAb positive subgroup. Endothelial function was tested by the reactive hyperemia index (RHI). Hashimoto's thyroiditis patients had lower RHI than healthy controls (1.73±0.42 vs 1.96±0.51, p<0.05). Hashimoto's thyroiditis with single TGAb positive patients had higher RHI than single TPOAb positive (1.98±0.57 vs. 1.69±0.33, p<0.05) and TGAB + TPOAb positive patients (1.98±0.57 vs. 1.68±0.42, p<0.05). RHI were negatively associated with total cholesterol (TC, r=-0.215, p<0.05), low density lipoprotein cholesterol (LDL-C, r=-0.268, p<0.05), triglyceride (TG, r=-0.192, p<0.05), and TPOAb (r=-0.288, p<0.05). In the regression analysis, LDL-C (ß=-0.146, p<0.05), TG (ß=-0.034, p<0.05) and TPOAb (ß=-0.001, p<0.05) were independently associated with RHI. Hashimoto's patients had poor endothelial function. TPOAb levels were negatively associated with endothelial function.

Homocysteine Levels are Associated with Endothelial Function in Newly Diagnosed Type 2 Diabetes Mellitus Patients.

Background: Endothelial dysfunction is the earliest indicator of atherosclerosis. Both type 2 diabetes mellitus (T2DM) and hyperhomocysteinemia (HHCY) are the risk factors of endothelial dysfunction. However, the combined effect of T2DM and HHCY on endothelial dysfunction is not clear. We investigated the endothelial function in T2DM patients with HHCY in this study. Material and Methods: Fifty newly diagnosed T2DM patients and 54 healthy subjects were recruited from Beijing Chaoyang hospital. T2DM patients were divided into two subgroups as T2DM + NHCY (n = 30) and T2DM + HHCY (n = 20) according to plasma homocysteine (HCY). HHCY was defined as plasma HCY level higher than 15 µmol/L. Endothelial function was measured by the reactive hyperemia index (RHI) with Endo PAT-2000. Results: Sex and age were matched between T2DM group and healthy controls. T2DM group had significantly higher HCY level (14.44 ± 4.30 vs. 12.09 ± 2.48 mmol/L, P < 0.05) and lower RHI (1.73 ± 0.50 vs. 2.05 ± 0.49, P < 0.01) than controls. In the subgroup analysis, T2DM with HHCY had significantly lower RHI than T2DM patients without HHCY (1.53 ± 0.20 vs. 1.86 ± 0.59, P < 0.05). RHI was negatively correlated with HCY (r = -0.325, P < 0.01), low-density lipoprotein cholesterol (LDL-C) (r = -0.268, P < 0.01), HbA1c (r = -0.219, P < 0.05), and HOMA-IR (r = -0.226, P < 0.05). Multiple linear regressions analysis was performed and HCY, LDL-C, HbA1c, and HOMA-IR were entered in the model. Analysis showed that HCY levels were independent negatively associated with RHI (ß = -0.032, P < 0.05). Conclusions: T2DM patients with HHCY had poor endothelial function. Serum HCY levels were negatively associated with RHI.

The Effects of Exenatide and Metformin on Endothelial Function in Newly Diagnosed Type 2 Diabetes Mellitus Patients: A Case-Control Study.

INTRODUCTION: Exenatide is a new antidiabetic glucagon-like peptide-1 receptor agonist. In addition to its hypoglycemic effect, exenatide may have a potential protective benefit on vascular endothelial function. This study attempted to compare the effects of exenatide and traditional antidiabetic drug metformin treatment on endothelial function in overweight patients with type 2 diabetes. METHODS: Ninety overweight patients with newly diagnosed type 2 diabetes were recruited; 45 patients received exenatide (Exe) treatment and 45 patients received metformin (Met) treatment for 12 weeks. The control groups included 37 overweight and 24 non-overweight individuals. The parameters of glucose and lipid metabolism and endothelial function were measured before and after treatment. Vascular endothelial dysfunction was measured by reactive hyperemia index. RESULTS: Newly diagnosed patients with type 2 diabetes had more serious vascular endothelial dysfunction than both overweight and normal-weight control groups. The levels of body mass index, glucose, HbA1c, homeostasis model assessment insulin resistance, and homeostasis model assessment ß-cell function were improved significantly by both exenatide and metformin treatment. Both exenatide and metformin treatment can improve vascular endothelial function (Exe group: 1.67 ± 0.52 vs 1.98 ± 0.67, P < 0.05; Met group: 1.68 ± 0.29 vs 1.82 ± 0.24, P < 0.05). Exenatide treatment was no less effective than metformin in improving endothelial function (0.31 ± 0.70 vs 0.13 ± 0.24, P > 0.05). CONCLUSIONS: Newly diagnosed patients with type 2 diabetes may have vascular endothelial dysfunction. Both exenatide and metformin treatment can improve vascular endothelial dysfunction, and exenatide was no less effective than metformin treatment.

Comparison of Exenatide and Metformin Monotherapy in Overweight/Obese Patients with Newly Diagnosed Type 2 Diabetes.

AIMS: The present study assessed the therapeutic effect of exenatide and metformin as the initial therapy on overweight/obese patients with newly diagnosed type 2 diabetes (T2D). METHODS: The prospective, nonrandomized, interventional study enrolled a total of 230 overweight or obese patients with newly diagnosed T2D who were administrated exenatide or metformin hydrochloride for 12 weeks. RESULTS: 224/230 patients, including 106 in the exenatide group and 118 in the metformin group, completed the 12-week treatment. Both exenatide and metformin significantly decreased the HbA1c levels in overweight/obese patients with newly diagnosed T2D (all P < 0.05). The reduction in HbA1c and the proportion of patients with HbA1c < 7.0% (53 mmol/mol) were higher in the exenatide group than in the metformin group (all P < 0.05). The exenatide treatment caused a greater decline in the body weight and BMI as compared to the metformin treatment (all P < 0.01). The exenatide treatment (ß = 0.41, P < 0.01) and baseline HbA1c level (ß = -0.84, P < 0.01) were independent influencing factors for the decrease in HbA1c level. CONCLUSIONS: For an initial therapy in overweight/obese patients with newly diagnosed T2D, exenatide causes a better glycemic control than metformin. This trial is registered with NCT03297879.

Clinical Study of Serum Homocysteine and Non-Alcoholic Fatty Liver Disease in Euglycemic Patients.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease. NAFLD includes a spectrum of hepatic pathologies: simple fatty liver, steatohepatitis and cirrhosis. Insulin resistance may contribute to NAFLD. The liver plays an important role in the production and metabolism of homocysteine (HCY), which is known to be an independent risk factor for cardiovascular disease. High HCY level can aggravate NAFLD by increasing the reactive oxygen species and activating oxidative stress. In this study, we investigated the relationship between HCY and NAFLD in euglycemic patients. MATERIAL AND METHODS A total of 1143 euglycemic patients were recruited: 519 patients with non-alcoholic fatty liver disease (NAFLD) and 624 sex and age-matched controls without NAFLD. RESULTS The NAFLD group had significantly higher HCY level (13.78±5.84 vs. 11.96±3.58 mmol/L, p<0.001), as well as higher body mass index (BMI), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminase (AST), fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for beta cell function (HOMA-B), and lower high density lipoprotein cholesterol (HDL-C). HCY level was positively correlated with HOMA-IR (r=0.239, p<0.001), TG (r=0.356, p<0.001) and negatively correlated with HDL-C (r=-0.161, p<0.001). In the logistic regression analysis, BMI (beta=0.345, p<0.001), HOMA-IR (beta=0.654, p<0.01), TG (beta=0.881, p<0.001), and HCY (beta=0.04, p=0.044) were the predictors of NAFLD. CONCLUSIONS Higher HCY level existed in NAFLD patients and was correlated with the severity of insulin resistance. HCY is an independent risk factor for NAFLD.

Exenatide treatment increases serum irisin levels in patients with obesity and newly diagnosed type 2 diabetes.

OBJECTIVE: Irisin is a myokine secreted by skeletal muscle during exercise. Abnormal serum irisin levels are associated with obesity and type 2 diabetes (T2D). This study investigated the changes in serum irisin in the obese patients with newly diagnosed T2D following glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide) treatment. METHODS: Fifty-four obese patients with T2D were treated with exenatide for 12weeks. The control group included 54 age-, sex-, and body mass index (BMI)-matched subjects with normal glucose tolerance. RESULTS: Patients with T2D had lower irisin than the control group (38.06 [29.29-53.79] vs. 58.01 [43.07-87.79] ng/mL, P<0.01]. Serum irisin was negatively associated with BMI (r=-0.178, P<0.05), fasting blood glucose (FBG; r=-0.170, P<0.05), and glycosylated hemoglobin (HbA1c; r=-0.189, P<0.01) in patients with T2D. Exenatide treatment markedly increased serum irisin by 19.28ng/mL (12.59-25.98) compared to baseline (P<0.01). Increased irisin was significantly correlated with decreased FBG and HbA1c after exenatide treatment (FBG: r=-0.35; HbA1c: r=-0.37; both P<0.05). CONCLUSIONS: Exenatide treatment significantly increased irisin in patients with T2D. Post-treatment changes in irisin were correlated with decreases in FBG and HbA1c. The upregulation of irisin might be a novel mechanism for the beneficial effects of exenatide in type 2 diabetic patients.

Potential harmful correlation between homocysteine and low-density lipoprotein cholesterol in patients with hypothyroidism.

OBJECTIVE: Hypothyroidism (HO) can induce metabolic dysfunctions related to insulin resistance and dyslipidemia. Our previous studies showed that homocysteine (Hcy) impaired the coronary endothelial function and that Hcy can promote chemokine expression and insulin resistance (IR) by inducing endoplasmic reticulum stress in human adipose tissue and hypothyroid patients. The aim of this study was to investigate the potential harmful correlation between plasma Hcy and low-density lipoprotein cholesterol (LDL-C) in patients with HO. METHODS: A total of 286 subjects were enrolled. All subjects were divided into the following 3 groups: HO group, subclinical hypothyroidism (SHO) group, and control group. Statistical analyses were carried out to evaluate the correlation between the plasma levels of Hcy and LDL-C in HO patients. The changes in the plasma Hcy levels and other metabolic parameters were measured before and after levothyroxine (L-T4) treatment. The relationship between the changes in the plasma Hcy level and the LDL-C level was also evaluated after L-T4 treatment. RESULTS: In the patients with HO, both the plasma Hcy and LDL-C levels were significantly higher than those of the controls. The plasma levels of Hcy were positively correlated with the LDL-C level in the HO group. L-T4 treatment resulted in a significant decrease in the BMI, total cholesterol (TC), LDL-C, triglycerides (TG), apolipoprotein B (ApoB), and Hcy levels. Moreover, the decrease in Hcy (ΔHcy) was positively correlated with decreased LDL-C (ΔLDL-C) levels after L-T4 treatment in HO patients. CONCLUSION: Our results suggest that the increased Hcy level was positively correlated with the LDL-C in the HO group. A potential harmful interaction may exist between Hcy and LDL-C under the HO condition. In addition to reducing the plasma levels of Hcy, L-T4 treatment exerts beneficial effects on patients with HO by improving dyslipidemia, including a decrease in the LDL-C level.

PPARα Agonist Fenofibrate Reduced the Secreting Load of ß-Cells in Hypertriglyceridemia Patients with Normal Glucose Tolerance.

Hypertriglyceridemia is an important risk factor associated with insulin resistance and ß-cell dysfunction. This study investigated the effects of hypertriglyceridemia and fenofibrate treatment on insulin sensitivity and ß-cell function in subjects with normal glucose tolerance. A total of 1974 subjects with normal glucose tolerance were divided into the normal TG group (NTG group, n = 1302) and hypertriglyceridemia group (HTG group, n = 672). Next, 92 patients selected randomly from 672 patients with hypertriglyceridemia were assigned to a 24-week fenofibrate treatment. The HTG group had increased waist circumference (WC), body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of ß-cell function (HOMA-ß) and decreased high-density lipoprotein cholesterol (HDL-C) compared with the NTG group (all P < 0.01). The 24-week fenofibrate treatment significantly decreased the WC, BMI, TG, HOMA-IR, and HOMA-ß levels and increased the HDL-C levels in the patients with hypertriglyceridemia (WC, BMI, and HOMA-IR: P < 0.05; TG, HDL-C, and HOMA-ß: P < 0.01). The fenofibrate treatment significantly alleviated insulin resistance and reduced the secreting load of ß-cells in the hypertriglyceridemia patients with normal glucose tolerance.

Levothyroxine treatment restored the decreased circulating fibroblast growth factor 21 levels in patients with hypothyroidism.

BACKGROUND AND AIMS: Fibroblast growth factor 21 (FGF21) is an important endogenous regulator of energy metabolism. Thyroid hormone has been shown to regulate hepatic FGF21 expression in rodents. The goal of this study was to evaluate the plasma FGF21 levels in participants with normal thyroid function, subclinical hypothyroidism, or overt hypothyroidism and to investigate the change of plasma FGF21 levels in patients with overt hypothyroidism after levothyroxine treatment. METHODS: A total of 473 drug-naive participants were recruited, including 250 healthy control subjects, 116 patients with subclinical hypothyroidism, and 107 patients with overt hypothyroidism. Thirty-eight patients with overt hypothyroidism were assigned to receive levothyroxine treatment. RESULTS: The overt hypothyroidism group had decreased FGF21 levels compared with the control and subclinical hypothyroidism groups (P<0.01). Levothyroxine treatment markedly attenuated the increased circulating levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hsCRP), and homeostasis model assessment index of insulin resistance (HOMA-IR) in patients with overt hypothyroidism. A significant increase in plasma FGF21 levels was observed after levothyroxine treatment (P<0.01). The change in FGF21 levels was correlated with the increase of FT3 and FT4 after levothyroxine treatment (FT3: r=0.44; FT4: r=0.53; all P<0.05). CONCLUSIONS: Levothyroxine treatment ameliorated metabolic disorders and restored the decreased circulating FGF21 levels in patients with overt hypothyroidism. The increase in FGF21 levels after levothyroxine treatment might be partly associated with the amelioration of metabolic disorders in patients with hypothyroidism.

Comparison of ß-cell dysfunction and insulin resistance correlating obesity with type 2 diabetes: A cross-sectional study.

AIM: To assess the contribution of ß-cell dysfunction and insulin resistance to type 2 diabetes (T2D) in obese and non-obese Chinese people. METHODS: In this cross-sectional study, we recruited 1384 newly diagnosed T2D patients and 1712 healthy controls. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). ß-cell function was estimated by homeostasis model assessment of ß-cell function (HOMA-ß) and 60min insulinogenic index (IGI60). We compared the insulin resistance and ß-cell function of obese and non-obese Chinese patients with and without T2D. RESULTS: 50.18% of control participants and 62.28% of T2D patients were obese (BMI≥25kg/m(2)). HOMA-IR, HOMA-ß and IGI60 were significantly higher in obese than non-obese, irrespective of T2D. Non-obese T2D patients had significantly greater HOMA-IR, and lower HOMA-ß and IGI60 than non-obese control participants. The obese T2D group had lower HOMA-ß and IGI60 than the obese control group. There was no significant difference in HOMA-IR between the obese T2D and obese control groups. Multivariate logistic regression analysis revealed that HOMA-IR was associated with T2D only in non-obese group, and HOMA-ß and IGI60 were associated with T2D in both non-obese and obese groups. CONCLUSIONS: HOMA-ß and IGI60 were associated with T2D in obese and non-obese patients, but HOMA-IR was associated with T2D in non-obese Chinese.

High prevalence of vitamin D deficiency in urban health checkup population.

BACKGROUND: Vitamin D deficiency is documented as a common health problem in the world. Limited data has been found on the prevalence of vitamin D deficiency in Beijing area. AIM: To investigate the prevalence s of vitamin D deficiency in urban Beijing residents and the seasonal and monthly serum 25(OH)D variation in this population. METHODS: This is an urban hospital based cross-sectional study lasting whole 2 years. 5531 (5-101 years old) urban Beijing residents for health checkup are recruited from December 9th, 2011 to December 8th, 2013. Each subject completed a questionnaire designed to quantify intake of vitamin D through food, vitamin D supplements, hours of sun exposure, sunscreen use over the past month. Serum 25(OH)D is statistically analyzed in accordance with gender, age, and time-lines. RESULTS: Vitamin D deficiency (Serum 25(OH)D level ≤20 ng/mL) and sever deficiency (Serum 25(OH)D level ≤ 10 ng/mL) are highly prevalent in this population. The prevalence of vitamin D deficiency is 87.1% and higher prevalence is found in female (89.0%) than male (84.9% P < 0.001). Severe vitamin D deficiency is also higher in female than male (59.3% and 42.7%, respectively, P < 0.001). Female under 20 and over 80 have lower 25(OH)D levels compared to 40-60 years old female (both P < 0.05). Severe vitamin D deficiency are also highly prevalence in this two group (60.9% and 54.1%) compared with 40-60 years old females (43.1%, both P < 0.05). Seasonal variation are also found in this population (P < 0.01). Autumn and summer have the higher 25(OH)D level than winter and spring in both genders (P < 0.001). Winter and spring have higher vitamin D deficiency and Severe deficiency than the other two seasons (P < 0.05). Serum 25(OH)D level peaks in October and troughed in April in both female and male. Lower serum 25(OH)D level are found in April than February (P < 0.05) in both gender. CONCLUSIONS: This is the first time to examine the prevalence of vitamin D deficiency among urban Beijing residents spanning the age spectrum. And Vitamin D deficiency and severe deficiency is found highly prevalent in this population, especially among females under 20 and older than 80 and in winter and spring seasons. Targeted prevention on vitamin D deficiency is urgent for this population.

Structure of lpg0406, a carboxymuconolactone decarboxylase family protein possibly involved in antioxidative response from Legionella pneumophila.

Lpg0406, a hypothetical protein from Legionella pneumophila, belongs to carboxymuconolactone decarboxylase (CMD) family. We determined the crystal structure of lpg0406 both in its apo and reduced form. The structures reveal that lpg0406 forms a hexamer and have disulfide exchange properties. The protein has an all-helical fold with a conserved thioredoxin-like active site CXXC motif and a proton relay system similar to that of alkylhydroperoxidase from Mycobacterium tuberculosis (MtAhpD), suggesting that lpg0406 might function as an enzyme with peroxidase activity and involved in antioxidant defense. A comparison of the size and the surface topology of the putative substrate-binding region between lpg0406 and MtAhpD indicates that the two enzymes accommodate the different substrate preferences. The structural findings will enhance understanding of the CMD family protein structure and its various functions.

Resveratrol prevents hepatic steatosis and endoplasmic reticulum stress and regulates the expression of genes involved in lipid metabolism, insulin resistance, and inflammation in rats.

Previous research demonstrated that resveratrol possesses promising properties for preventing obesity. Endoplasmic reticulum (ER) stress was proposed to be involved in the pathophysiology of both obesity and hepatic steatosis. In the current study, we hypothesized that resveratrol could protect against high-fat diet (HFD)-induced hepatic steatosis and ER stress and regulate the expression of genes related to hepatic steatosis. Rats were fed either a control diet or a HFD for 12 weeks. After 4 weeks, HFD-fed rats were treated with either resveratrol or vehicle for 8 weeks. Body weight, serum metabolic parameters, hepatic histopathology, and hepatic ER stress markers were evaluated. Moreover, an RT2 Profiler Fatty Liver PCR Array was performed to investigate the mRNA expressions of 84 genes related to hepatic steatosis. Our work showed that resveratrol prevented dyslipidemia and hepatic steatosis induced by HFD. Resveratrol significantly decreased activating transcription factor 4, C/EBP-homologous protein and immunoglobulin binding protein levels, which were elevated by the HFD. Resveratrol also decreased PKR-like ER kinase phosphorylation, although it was not affected by the HFD. Furthermore, resveratrol increased the expression of peroxisome proliferator-activated receptor δ, while decreasing the expression of ATP citrate lyase, suppressor of cytokine signaling-3, and interleukin-1ß. Our data suggest that resveratrol can prevent hepatic ER stress and regulate the expression of peroxisome proliferator-activated receptor δ, ATP citrate lyase, suppressor of cytokine signaling-3, tumor necrosis factor α, and interleukin-1ß in diet-induced obese rats, and these effects likely contribute to resveratrol's protective function against excessive accumulation of fat in the liver.