Survival of Chinese people with type 2 diabetes and diabetic kidney disease: a cohort of 12 -year follow-up.

BACKGROUND: The prevalence of type 2 diabetes has grown significantly in China. However, little is known about the survival outcome of people with type 2 diabetes and diabetic kidney disease (DKD). The purpose of this study is to examine the survival of this population and the risk factors for mortality in one suburb cohort of Beijing, China. METHODS: Four hundred and forty-five people with DKD (48.8% male, age at onset of diabetes 48.8 ± 11.0 years, age at enrollment 57.5 ± 11.6 years) were enrolled in one suburb of Beijing, China between January 1st, 2003 and December 31st, 2015. Mortality ascertainment was censored by December 31st, 2015. Survival analysis was performed by Kaplan-Meier analysis, and Cox proportional hazards regression models were served for risk factor analysis of mortality. The Chiang method was used to estimate life expectancy by age. RESULTS: A total of 78 deaths were identified during the 3232 person-years of follow-up. Multivariate Cox regression analysis showed significantly higher risks of mortality with respect to older age, higher systolic blood pressure (SBP), lower body mass index (BMI) and lower estimated glomerular filtration rate (eGFR). The life expectancy at age of 50 was estimated to be 12.3 (95%, CI: 9.0-16.1) years. Circulatory disease was the leading cause of death in this population (accounting for 43.6% of all deaths), followed by diabetic complications (33.3%) and respiratory disease (6.4%). CONCLUSIONS: Data from one Chinese cohort from 2003 through 2015 showed that people with DKD faced higher risk of death and shorter life expectancy. Factors significantly increasing risk of death included older age, higher SBP, lower BMI and lower eGFR. There is an urgent need to early detection, closely monitoring and effective intervention on DKD.

HDL in diabetic nephropathy has less effect in endothelial repairing than diabetes without complications.

BACKGROUND: Diabetic nephropathy has a high cardiovascular risk with a low-level HDL(high density lipoprotein) in epidemiologic studies. Glycated HDL in diabetes can diminish the capacity to stimulate endothelial cell migration, but the mechanism has not been adequately explored in diabetic nephropathy. We performed this study to find out whether HDL in diabetic nephropathy is more dysfunctional than HDL in diabetes without complications. METHODS: Endothelial cells were treated with N-HDL (normal), D-HDL (T2DM[type 2 diabetes mellitus] without complications), DN-HDL (T2DM nephropathy), N-apoA-I (normal apoA-I), and G-apoA-I (glycated apoA-I in vitro). Cell migration capacity was measured with wound-healing and transwell migration assay in vitro and electric carotid injury model in vivo. Protein glycation levels were measured with nanoLC-MS/MS. PI3K expression and Akt phosphorylation were analyzed by western blot. RESULTS: In wound-healing assay, DN-HDL showed a 17.12% decrease compared with D-HDL (p < 0.05). DN-HDL showed a 29.85% decrease in comparison with D-HDL (p < 0.001) in transwell assay. In the electric carotid injury model, D-HDL and DN-HDL impaired the re-endothelialization capacity; DN-HDL was less effective than D-HDL. Meanwhile, DN-HDL was found to have a significantly higher protein glycation level than D-HDL (p < 0.001). PI3K expression and Akt phosphorylation were reduced significantly in DN-HDL in comparison with D-HDL and N-HDL. CONCLUSIONS: We found that HDL from diabetic nephropathy has a higher level of glycation and induced less cell migration in vitro and in vivo compared with that from diabetes without nephropathy. This finding suggests that diabetic nephropathy has higher levels of glycated HDL and partially explains why patients with DN have a higher risk of cardiovascular disease.

Association Between Indices of Body Composition and Metabolically Unhealthy Phenotype in China: A Cross-Sectional Study.

Introduction: Body composition is closely related to metabolic health status. Visceral adipose tissue (VAT) dysfunction contributes to metabolic syndrome. However, results regarding subcutaneous adipose tissue (SAT) and skeletal muscle are controversial. We aimed to determine the association of indices of body composition with abnormal metabolic phenotype in China. Methods: A total of 3, 954 subjects (age 50.2 ± 11.7 years) with body mass index (BMI) more than 18.5 kg/m2 from Pinggu Metabolic Disease Study were analyzed. Quantitative computed tomography (QCT) was performed to measure total adipose tissue (TAT), VAT, SAT area, and lumbar skeletal muscle area (SMA). Participants were divided into six groups on the basis of BMI category (normal weight/overweight/obesity) and metabolic status (healthy/unhealthy), as defined by the presence or absence of components of the metabolic syndrome by Chinese Diabetes Society criteria. Results: 63.4%, 39.5%, and 23.3% participants were classified as metabolically healthy phenotype in individuals with normal weight, overweight and obese, respectively. Individuals in the highest TAT, VAT, and VAT/TAT ratio category had higher risk of being metabolically unhealthy than individuals in the lowest group (all p<0.01). While, risk for metabolically unhealthy was reduced significantly in the highest SMA/TAT ratio category when compared with the lowest category in individuals with normal wight and overweight (both p<0.05). Risk for metabolically unhealthy was reduced significantly in the highest SAT category when compared with the lowest category (OR=0.555, 95%CI: 0.360-0.856, p=0.008) in individuals with obese after adjustment for age, sex and BMI. However, skeletal muscle index (SMI) showed no significant association with the metabolically healthy status in different BMI categories (p>0.05). The VAT and VAT/TAT ratio were better diagnostic values of indicators to differentiate metabolically unhealthy subjects from controls compared with other indicators, such as TAT, SAT, SMI, SMA/TAT ratio. Conclusions: Higher visceral adipose tissue was closely associated with metabolically unhealthy phenotype in Chinese adults. Subcutaneous adipose tissue might be a protective factor for metabolic health status only in obese individuals.

Novel glucose-lowering drugs for non-alcoholic fatty liver disease.

BACKGROUND: The efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) is unknown. AIM: To evaluate the efficacy of glucose-lowering drugs dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors in treating NAFLD and to perform a comparison between these treatments. METHODS: Electronic databases were systematically searched. The inclusion criteria were: Randomized controlled trials comparing DPP-4 inhibitors, GLP-1 RAs, or SGLT2 inhibitors against placebo or other active glucose-lowering drugs in NAFLD patients, with outcomes of changes in liver enzyme [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] from baseline. RESULTS: Nineteen studies were finally included in this meta-analysis. Compared with placebo or other active glucose-lowering drug treatment, treatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors all led to a significant decrease in ALT change and AST change from baseline. The difference between the DPP-4 inhibitor and SGLT2 inhibitor groups in ALT change was significant in favor of DPP-4 inhibitor treatment (P < 0.05). The trends of reduction in magnetic resonance imaging proton density fat fraction and visceral fat area changes were also observed in all the novel glucose-lowering agent treatment groups. CONCLUSION: Treatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors resulted in improvements in serum ALT and AST levels and body fat composition, indicating a beneficial effect in improving liver injury and reducing liver fat in NAFLD patients.

The impact of ferritin on the disassociation of HbA1c and mean plasma glucose.

OBJECTIVE: To explore the impact of ferritin level on the disassociation of glycated hemoglobin A1c (HbA1c) and mean plasma glucose (MPG). RESEACH DESIGN AND METHODS: We used a 2012-2013 cross-sectional survey conducted in Pinggu district, Beijing including 3095 Chinese participants aged 25-75 years. We categorized their glycemic status by interviewing for diagnosed diabetes and by measuring HbA1c, fasting plasma glucose (FPG), and 2-hours post-load plasma glucose (2-hours PPG). We fitted a multivariable regression model to explore the impact of ferritin on the association of HbA1c or glycated albumin (GA) and mean plasma glucose. RESULTS: A total of 5.65% of participants were diagnosed as diabetes using HbA1c criteria, and 9.79% using oral glucose tolerance test criteria. Compared with males, females had significantly lower hemoglobin levels (159.82 ± 11.56 vs 135.93 ± 12.62) and lower ferritin levels (113.00 [68.55, 185.50] vs 33.40 [12.40, 70.13]). Linear regression analysis performed in different groups classified by different diagnose criterion indicated that the correlation between MPG and HbA1c differs in different tertiles of ferritin (lowest vs middle vs highest: R2 = 0.507 vs 0.645 vs 0.687 in female; R2 = 0.415 vs 0.715 vs 0.615 in male), and the association between MPG and HbA1c diminished in the lowest tertile of ferritin. CONCLUSIONS: Ferritin level might affect the association between glucose and HbA1c, which should be taken into account when using HbA1c as a diagnosis criterion for diabetes and prediabetes.

Sex- and age-related trajectories of the adult human gut microbiota shared across populations of different ethnicities.

Lifelong sex- and age-related trajectories of the human gut microbiota remain largely unexplored. Using metagenomics, we derived the gut microbial composition of 2,338 adults (26-76 years) from a Han Chinese population-based cohort where metabolic health, hormone levels and aspects of their lifestyles were also recorded. In this cohort, and in three independent cohorts distributed across China, Israel and the Netherlands, we observed sex differences in the gut microbial composition and a shared age-related decrease in sex-dependent differences in gut microbiota. Compared to men, the gut microbiota of premenopausal women exhibited higher microbial diversity and higher abundances of multiple species known to have beneficial effects on host metabolism. We also found consistent sex-independent, age-related gut microbial characteristics across all populations, with the presence of members of the oral microbiota being the strongest indicator of older chronological age. Our findings highlight the existence of sex- and age-related trajectories in the human gut microbiota that are shared between populations of different ethnicities and emphasize the pivotal links between sex hormones, gut microbiota and host metabolism.

[Antihypertensive effect of metformin in essential hypertensive patients with hyperinsulinemia.].

OBJECTIVE: To investigate the possibility and utility of metformin alone or in combination with fosinopril to reduce blood pressure in patients with essential hypertension. METHODS: A total of 140 cases of non-diabetic essential hypertension with hyperinsulinemia were recruited and randomly assigned to two groups: a group of 68 treated with metformin 500 mg tid and a group of 72 treated with fosinopril 10 mg qd. The duration of the treatment was 8 weeks. Combination therapy with the two drugs was used after 4 weeks of treatment if needed. If the target goals of systolic blood pressure (SBP) < 140 mm Hg (1 mm Hg = 0.133 kPa) and/or diastolic blood pressure (DBP) < 90 mm Hg were not attained 4 weeks, combination therapy with two drugs was used in either group in the next 4 weeks. The changes of blood pressure and insulin sensitivity of the two groups were observed before and after treatment. RESULTS: (1) After 4 weeks of treatment, SBP in metformin group and fosinopril group decreased by (13.0 +/- 1.2) mm Hg and (15.4 +/- 1.4) mm Hg, and DBP decreased by (9.0 +/- 1.0) mm Hg and (10.4 +/- 1.1) mm Hg respectively. After 8 weeks of treatment, SBP in metformin group and fosinopril group decreased by (17.8 +/- 1.5) mm Hg and (20.9 +/- 1.5) mm Hg, and DBP decreased by (13.2 +/- 0.9) mm Hg and (15.3 +/- 1.1) mm Hg respectively. There was no significant difference in the decline of blood pressure between the two groups (P > 0.05). The rates of combination therapy were both 54% in the two groups. (2) Fasting insulin as well as 30 min and 120 min insulin levels after oral glucose tolerance test and insulin area under the curve in the metformin group were significantly reduced after 4 and 8 weeks of treatment as compared with those of baseline (P < 0.05 and P < 0.01). In the fosinopril group, however, they decreased only after 8 weeks treatment (P < 0.05). The insulin action index in the metformin group was higher than that in the fosinopril group after 4 weeks of treatment (P < 0.05), but there was no significant difference between the two groups after 8 weeks of treatment (P > 0.05). CONCLUSION: Metformin and fosinopril have similar antihypertensive effect and a good synergy in essential hypertension with hyperinsulinemia.

Prevalence of Thyroid Dysfunction in a Chinese Population with Different Glucose Intolerance Status: A Community-Based Cross-Sectional Study.

AIM: Impaired glucose metabolism and thyroid dysfunction (TD) are the two most common chronic metabolic disorders. This study aimed to investigate the epidemiological characteristics of TD in different status of glucose tolerance in a community-based Chinese population and to understand the association between TD and glucose metabolism. METHODS: A community-based population study of metabolic disease was conducted from June 2013 to September 2014 in Beijing, China. Residents aged 26-76 years were selected according to gender and age composition using multi-stage stratified random sampling process. All participants underwent serum thyroid function and thyroid-associated antibody tests. The status of glucose tolerance was determined using 75g-oral glucose tolerance test. Chi-square test was used to compare the differences in prevalence. Multivariate logistic regression analysis was used to determine the impact of insulin resistance (IR) on thyroid function. RESULTS: By analyzing 3986 participants who were included in the survey, the prevalence of type 2 diabetes (T2DM) and pre-diabetes (pre-DM) was 18.59% and 26.79%, respectively. The prevalence of TD was 8.81%, with overt hyperthyroidism accounting for 0.38%; subclinical hyperthyroidism, 1.86%; overt hypothyroidism, 0.70%; and subclinical hypothyroidism, 5.87%. The prevalence of TD increased with gradually deteriorated glucose tolerance (7.63% in those with normal glucose tolerance, 9.27% in pre-DM, and 11.61% in T2DM) in both men and women. Each unit of higher HOMA-IR was associated with 7% higher likelihood of having subclinical hypothyroidism. CONCLUSION: The coexisting of TD with T2DM and pre-DM is high in this community-based Chinese population, suggesting a close relationship between TD and glucose metabolism.

The Morbidity and Comorbidity of Nonalcoholic Fatty Liver Disease and Different Glucose Intolerance Strata in a Community-Based Chinese Population.

Objective: To investigate the morbidity and comorbidity of nonalcoholic fatty liver disease (NAFLD) and different glucose intolerance strata in a community-based population and to explore the association between glucose tolerance levels and NAFLD. Methods: A community-based cohort established for Pinggu Metabolic Disease Study in a suburb of Beijing, China, was established from September 2013 to July 2014 using a random sampling method. Participants were eligible if they were born in Pinggu and had been living there for at least 5 years within the age range of 26-76 years. A 75 grams oral glucose tolerance test was used to determine the strata of glucose tolerance. Unenhanced abdominal computed tomography scan was performed to identify NAFLD. Results: A total of 3122 subjects were included in this analysis. The prevalence of NAFLD was 22.68% (27.58% vs. 19.97% among men and women). The prevalence of type 2 diabetes (T2D) was 18.03% (20.83% vs. 16.22% among men and women). Up to 7.21% of residents had both T2D and NAFLD. 39.96% of diabetic patients and 28.77% of prediabetic patients combined with NAFLD. Compared with adults with normal glucose tolerance, the incidence of NAFLD in T2D patients was more than three times higher after adjusting for sex, age, body mass index (BMI), sedentary time, and dietary habit [odds ratio (OR) = 3.58, confidence interval (95% CI) 2.80-4.58, P < 0.001]. NAFLD was also more common in individuals with prediabetes, especially patients with impaired glucose tolerance (IGT) (OR = 2.27, 1.75-2.95) or impaired fasting glucose+IGT (OR = 2.78, 1.92-4.03). Conclusions: The morbidity and comorbidity of NAFLD and glucose intolerance are high in the Pinggu population in northern China, highlighting the importance of early prevention and treatment of these two diseases at the same time.

The Prevalence of Osteoporosis Tested by Quantitative Computed Tomography in Patients With Different Glucose Tolerances.

AIM: The objectives of the present study were to compare bone characteristics with quantitative computed tomography (QCT) and other metabolic factors relevant to bone health in subjects with normal glucose tolerance, impaired glucose tolerance (IGT), and diabetes mellitus (DM) and to evaluate the association of various laboratory factors with bone characteristics qualified by QCT. METHODS: This cross-sectional population-based survey of diabetes and metabolic syndrome was conducted in Pinggu, China. The oral glucose tolerance test was conducted and QCT was tested. The volumetric bone mineral density (vBMD) of lumbar vertebrae 2 through 4 was measured. RESULTS: Among the 4001 eligible participants, the average age was 47.41 ± 11.86 years. The prevalence of osteoporosis evaluated by QCT was 10.6% in the normal glucose tolerance group, 14.8% in the IGT group, and 16.9% in the DM group. Multivariate linear regression analysis showed that age was negatively associated with vBMD, whereas body mass index and waist-hip ratio were positively associated with vBMD across all participants. However, the levels of hemoglobin A1c, fasting plasma glucose, and postprandial glucose were not associated with vBMD after adjusting for sex, age, systolic and diastolic blood pressure, body mass index, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, FT4, FT3, thyroid-stimulating hormone, urine albumin-to-creatinine ratio, creatinine, and serum uric acid. CONCLUSIONS: We found that the prevalence of osteoporosis evaluated by QCT was 10.6% in the normal glucose tolerance group, 14.8% in the IGT group, and 16.9% in the DM group. The levels of hemoglobin A1c, fasting plasma glucose, and postprandial glucose were not associated with vBMD after adjusting for metabolic factors in a Chinese sample.

The Association Between Serum Thyrotropin Within the Reference Range and Metabolic Syndrome in a Community-Based Chinese Population.

PURPOSE: We aimed to ascertain the association between thyrotropin (TSH) levels in euthyroid state and the prevalence of metabolic syndrome (MetS) in a community-based Chinese population. PARTICIPANTS AND METHODS: Based on a large and well-characterized community cohort in Beijing, China, 1831 men and 1742 women with serum TSH levels within the reference range (0.50-4.78 µIU/mL) were stratified by quartiles of TSH (Q1-4). MetS was identified according to the criteria of International Diabetes Federation guidelines. Poisson regression models were used to estimate the association between serum TSH and the prevalence of MetS and its components before and after adjustment for potential confounding factors. The reported association was measured using the prevalence ratio (PR) with its respective 95% confidence interval (95% CI). RESULTS: The prevalence of MetS in euthyroid population across TSH quartiles (Q1-4) was 38.9%, 44.6%, 41.0%, and 47.7%, respectively, in men (P = 0.045), and 47.7%, 46.6%, 46.9%, and 54.6%, respectively, in women (P = 0.032). Compared with the reference group TSH-Q1, the prevalence of MetS was higher among TSH-Q4 group both in men (PR = 1.27; 95% CI: 1.09, 1.48, P = 0.002) and women (PR = 1.21; 95% CI: 1.07, 1.37, P = 0.003) even after adjustment for age, lifestyle factors, serum levels of free triiodothyronine (FT3), and free thyroxine (FT4). Most of the components of MetS were common in higher serum TSH levels within the normal range. CONCLUSION: The prevalence of MetS and most of its components increased in the higher TSH group in euthyroid Chinese population.