Safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese: a randomized, double-blind, placebo-controlled, multiple-dose phase 1b study.

BACKGROUND: TG103, a glucagon-like peptide-1 analog, is being investigated as an option for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese without diabetes. METHODS: In this randomized, double-blind, placebo-controlled, multiple-dose phase 1b study, participants aged 18-75 years with a body-mass index (BMI) ≥ 26.0 kg/m2 and body weight ≥ 60 kg were enrolled from three centers in China. The study included three cohorts, and in each cohort, eligible participants were randomly assigned (3:1) to one of three once-weekly subcutaneous TG103 groups (15.0, 22.5 and 30.0 mg) or matched placebo, without lifestyle interventions. In each cohort, the doses of TG103 were escalated in 1-week intervals to the desired dose over 1 to 4 weeks. Then participants were treated at the target dose until week 12 and then followed up for 2 weeks. The primary endpoint was safety and tolerability assessed by the incidence and severity of adverse events (AEs) from baseline to the end of the follow-up period. Secondary endpoints included pharmacokinetic and pharmacodynamic profiles of TG103 and the occurrence of anti-drug antibodies to TG103. RESULTS: A total of 147 participants were screened, and 48 participants were randomly assigned to TG103 (15.0, 22.5 and 30.0 mg groups, n = 12 per group) or placebo (n = 12). The mean (standard deviation, SD) age of the participants was 33.9 (10.0) years; the mean bodyweight was 81.65 (10.50) kg, and the mean BMI was 29.8 (2.5) kg/m2. A total of 466 AEs occurred in 45 of the 48 participants, with 35 (97.2%) in the TG103 group and 10 (83.3%) in the pooled placebo group. Most AEs were grade 1 or 2 in severity, and there were no serious adverse events (SAEs), AEs leading to death, or AEs leading to discontinuation of treatment. The steady-state exposure of TG103 increased with increasing dose and was proportional to Cmax,ss, AUCss, AUC0-t and AUC0-inf. The mean values of Cmax,ss ranged from 951 to 1690 ng/mL, AUC0-t ranged from 150 to 321 µg*h/mL, and AUC0-inf ranged from 159 to 340 µg*h/mL. TG103 had a half-life of 110-116 h, with a median Tmax of 36-48 h. After treatment for 12 weeks, the mean (SD) values of weight loss from baseline in the TG103 15.0 mg, 22.5 mg and 30.0 mg groups were 5.65 (3.30) kg, 5.35 (3.39) kg and 5.13 (2.56) kg, respectively, and that in the placebo group was 1.37 (2.13) kg. The least square mean percent weight loss from baseline to D85 in all the TG103 groups was more than 5% with p < 0.05 for all comparisons with placebo. CONCLUSIONS: In this trial, all three doses of once-weekly TG103 were well tolerated with an acceptable safety profile. TG103 demonstrated preliminary 12-week body weight loss without lifestyle interventions, thus showing great potential for the treatment of overweight and obesity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04855292. Registered on April 22, 2021.

Independent and interactive associations of heart rate and obesity with type 2 diabetes mellites: A population-based study.

BACKGROUND: Although obesity and heart rate (HR) were closely related to the prevalence and development of type 2 diabetes mllitus (T2DM), few studies have shown a co-association effect of them on T2DM. We aimed at assessing the interactive effects of HR and obesity with prevalence of T2DM in Chinese population, providing the exact cutpoint of the risk threshold for blood glucose with high HR. MATERIALS AND METHODS: In the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal study (REACTION) cohorts (N = 8398), the relationship between HR and T2DM was explored by linear regression, logistic regression, and restricted cubic spline, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Interaction terms between HR and body mass index (BMI) and HR and waist circumference (WC) were introduced into the logistic regression model. RESULTS: In those with HR > 88.0 beats/min, fasting plasma glucose and oral glucose tolerance tests were significantly correlated with HR, and the prevalence of T2DM was highly correlated with HR (all p < .05). There were interactive associations of HR and obesity in patients with T2DM with HR < 74 beats/min. CONCLUSION: High HR was in interaction with obesity, associating with prevalence of T2DM. The newly subdivided risk threshold for HR with T2DM might be HR > 88 beats/minute.

Glucose Metabolism Indices and the Development of Chronic Kidney Disease: A Cohort Study of Middle-Aged and Elderly Chinese Persons.

Objective: Chronic kidney disease (CKD) has become a major global health issue, and abnormalities of glucose metabolism are a risk factor responsible for development of CKD. We aimed to investigate associations between glucose metabolism indices and CKD in a Chinese population and determine which index is superior for predicting incident CKD. Methods: We performed a community-based population on 5232 subjects aged ≥40 years without baseline CKD. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g. We examined the associations of glucose metabolism indices, including fasting plasma glucose (FPG), 2-hour (2 h) oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-ß and the development of CKD. Results: With an average follow-up of 3.6 years, 6.4% of the subjects developed CKD. Pearson's correlation analysis revealed that FPG, HbA1c, fasting insulin, and HOMA-IR were all significantly correlated with UACR and eGFR. The association persisted in multivariate linear regression analysis adjusted for age and sex. Compared with other glucose indices, HOMA-IR exhibited the strongest associations with CKD in COX multivariate regression analysis (HR = 1.17, 95% CI: 1.04-1.31). Conclusion: HOMA-IR is superior to other routine indices of glucose metabolism for predicting the development of CKD in middle-aged Chinese persons. Screening with HOMA-IR may help prevent the development of CKD in the general population.

Fatty Liver Index and Its Association with 10-Year Atherosclerotic Cardiovascular Disease Risk: Insights from a Population-Based Cross-Sectional Study in China.

This cross-sectional study aimed to investigate the association between non-alcoholic fatty liver disease (NAFLD) and atherosclerotic cardiovascular disease (ASCVD), a global public health concern. A total of 9044 out of 10,104 adults from Guangzhou, China, were included in the analysis. We utilized the fatty liver index (FLI), a noninvasive indicator of NAFLD, and the pooled cohort equations (PCE) based on the 2013 ACC/AHA Guideline, the China-PAR model, and the Framingham Risk Score to assess the 10-year ASCVD risk. The results demonstrated a significant association between FLI and 10-year ASCVD risk (p < 0.001). Adjusted for age, individuals with high FLI (≥60) had an odds ratio of 3.91 (95% CI 2.52-6.08) compared to those with low FLI (<30). These findings persisted after adjusting for metabolic indicators. Notably, this association was consistently observed across all three risk prediction models: the PCE model, the China-PAR model, and the Framingham Risk Score. In conclusion, our study provides evidence supporting FLI as a reliable indicator of increased 10-year ASCVD risk in Chinese NAFLD patients. FLI serves as a valuable marker for early detection of ASCVD, highlighting its potential in clinical practice for risk assessment and prevention strategies.

The association of liver enzymes with diabetes mellitus risk in different obesity subgroups: A population-based study.

Background: Numerous observational studies have shown that liver enzymes correlated with diabetes mellitus (DM) risk significantly, but limited studies showed whether different obesity subgroups present the same correlation. Our objective was to evaluate the association of liver enzymes with DM risk in different obesity subgroups based on a middle-aged Chinese population. Methods: We conducted a population-based cross-sectional study and surveyed 9,916 people aged 40 years and above. A two-slope linear regression model was used to analyze the cutoff points of obesity in DM risk. Restricted cubic splines were used to analyze the correlation between liver enzymes and DM risk in different obesity categories. The odds ratios and 95% confidence intervals (CIs) were calculated using the logistic regression model. Results: The cutoff points of body mass index (BMI) and waist circumference were 30.55 kg/m2 and 98.99 cm for DM risk, respectively. The serum gamma-glutamyl transferase (GGT) concentration was positively correlated with DM risk in the subgroups with waist circumference <98.99 cm [OR = 1.04, 95% CI (1.03-1.05)], BMI <30.55 kg/m2 [OR = 1.04, 95% CI (1.03-1.05)], and BMI ≥30.55 kg/m2 [OR = 1.18, 95% CI (1.04-1.39)], but not in the subgroup with waist circumference ≥98.99 cm. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations have no significant correlation with the risk of diabetes in all groups. Conclusion: The results showed that serum GGT concentration was correlated with DM risk but not with AST or ALT in the middle-aged population. However, the correlation disappeared when waist circumference was over 98.99 cm, and serum GGT concentration had a limited value for DM risk in waist circumference over 98.99 cm.

Development and validation of a nomogram for assessing risk of isolated high 2-hour plasma glucose.

A tool was constructed to assess need of an oral glucose tolerance test (OGTT) in patients whose fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are normal. Data was collected from the longitudinal REACTION study conducted from June to November 2011 (14,686 subjects, aged ≥ 40 y). In people without a prior history of diabetes, isolated high 2-hour plasma glucose was defined as 2-hour plasma glucose ≥ 11.1 mmol/L, FPG < 7.0 mmol/L, and HbA1c < 6.5%. A predictive nomogram for high 2-hour plasma glucose was developed via stepwise logistic regression. Discrimination and calibration of the nomogram were evaluated by the area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow test; performance was externally validated in Northeast China. Parameters in the model included gender, age, drinking status, marriage status, history of hypertension and hyperlipidemia, waist-to-hip ratio, FPG, and HbA1c. All variables were noninvasive, except FPG and HbA1c. The AUC of the nomogram for isolated high 2-hour plasma glucose was 0.759 (0.727-0.791) in the development dataset. The AUCs of the internal and externally validation datasets were 0.781 (0.712-0.833) and 0.803 (0.778-0.829), respectively. Application of the nomogram during the validation study showed good calibration, and the decision curve analysis indicated that the nomogram was clinically useful. This practical nomogram model may be a reliable screening tool to detect isolated high 2-hour plasma glucose for individualized assessment in patients with normal FPG and HbA1c. It should simplify clinical practice, and help clinicians in decision-making.

Association of education levels with the risk of hypertension and hypertension control: a nationwide cohort study in Chinese adults.

BACKGROUND: Education attainment can improve life expectancy and guide healthy behaviours throughout an entire lifetime. A nationwide longitudinal study of the association of education status with the risk of hypertension and its control in China is lacking. METHODS: The China Cardiometabolic Disease and Cancer Cohort Study is a multicentre, population-based, prospective cohort study. We performed the baseline survey from 2011 to 2012. A follow-up visit was conducted during 2014-2016. 101 959 subjects were included in the final data analyses. Cox proportional hazards regression was used to examine the associations of education levels with the risk of hypertension and uncontrolled hypertension. RESULTS: During follow-up, 11 189 (19.9%) participants had developed hypertension among subjects without hypertension at baseline. Among the participants with hypertension at baseline, only 40.6% had controlled hypertension. Compared with the participants' education level at elementary school and below, the multivariable-adjusted HR for incident hypertension was 0.76 (95% CI, 0.72 to 0.80) in those with a middle school education level and 0.67 (95% CI, 0.63 to 0.70) in those with a high school degree or above. Correspondingly, multivariable-adjusted HRs associated with uncontrolled hypertension were 0.90 (95% CI, 0.87 to 0.92) in participants with a middle school education level and 0.85 (95% CI, 0.82 to 0.88) in participants with a high school degree or above level. CONCLUSION: Participants with education attainment at elementary school and below exhibited excess risks of newly diagnosed hypertension and worse blood pressure control compared with individuals with education attainment at middle school or above.

Lipid Parameters and the Development of Chronic Kidney Disease: A Prospective Cohort Study in Middle-Aged and Elderly Chinese Individuals.

Epidemiological evidence suggests that lipid parameters are related to the progression of chronic kidney disease (CKD). Nevertheless, prospective studies that comprehensively assess the effect of routinely available lipid measures on the development of CKD are lacking. The aim of this study was to longitudinally assess the influence of lipid metabolism indicators on the presence of CKD in a large community-based population. We conducted a prospective cohort study at Sun Yat-sen Memorial Hospital, China, with 5345 patients of 40 years or older. Cox regression models were conducted, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess lipid parameters and their relationship with the incidence of CKD. During the follow-up period, 340 (6.4%) subjects developed CKD. The incidence of CKD increased progressively with quartile values of triglyceride (TG), the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (non-HDL-C/HDL-C) and the ratio of TG to HDL-C, but decreased with HDL-C quartiles (p < 0.0001 for all trends). Pearson's correlation analysis and multiple regression analyses indicated that these parameters were also associated with various indicators of kidney function. Moreover, we found that among all the lipid parameters, TG/HDL-C emerged as the most effective predictor of CKD. In conclusion, our findings suggest that TG/HDL-C better predicts the incidence of CKD in middle-aged and elderly Chinese individuals than other lipid parameters tested in the study.

Galectin-3/adiponectin as a new biological indicator for assessing the risk of type 2 diabetes: a cross-sectional study in a community population.

OBJECTIVE: This study aimed to explore the association between the risk of newly diagnosed type 2 diabetes and galectin-3 and adiponectin and to investigate whether their joint action shows a favorable diabetes assessment performance. METHODS: We conducted a community-based study in 135 newly diagnosed patients with type 2 diabetes and 270 age- and sex-matched nondiabetic patients. Odds ratios and 95% confidence intervals were determined using logistic regression analysis. Receiver operating characteristic curve, decision curve analysis and calibration plot were used to explore their efficacy and clinical utility for models. RESULTS: High quartiles of galectin-3/adiponectin (quartile 4 vs 1: OR 2.43 [95% CIs: 1.21-5.00]) showed the strongest correlation with an increased risk of type 2 diabetes in the total population, which was consistent in the older population (age≥50 years old) in adjustment models. The combination + lipids + galectin-3/adiponectin model (AUC = 0.72 [95% CIs: 0.66-0.77]) displayed better diabetes assessment performance than the other two models. CONCLUSIONS: High galectin-3 and low adiponectin levels were associated with the high risk of diabetes, and their joint action was a superior promising factor for evaluating diabetes risk. The diabetes discriminative strength of galectin-3/adiponectin was better in the older population than the younger.

The Risk Threshold for Hemoglobin A1c Associated With Albuminuria: A Population-Based Study in China.

Background: Diabetic kidney disease (DKD) is a kind of common microvascular complication of diabetes. This study aims to explore the possible links between blood sugar level and albuminuria, providing the exact cut point of the "risk threshold" for blood glucose with DKD. Methods: The relationship between blood glucose and albuminuria was modeled using linear and logistic regression in the REACTION study cohorts (N= 8932). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. Two-slope linear regression was used to simulate associations between blood glucose and ACR. Results: We found that the increase in ACR was accompanied by increased HbA1c, with a turning point at 5.5%. The positive correlation remained highly significant (P<0.001) when adjusted for age, sex, marital status, education, smoking status, drinking status, BMI, waistline, SBP and DBP. In subgroup analyses including gender, obesity, hypertension, and smoking habits, the relationship was significant and stable. Conclusions: We determined a risk threshold for HbA1c associated with albuminuria in a Chinese population over the age of 40. HbA1c ≥ 5.5% was positively and independently associated with ACR. These results suggest the necessity of early blood glucose control and renal function screening for DKD in at-risk populations.

Association between uric acid lowering and renal function progression: a longitudinal study.

BACKGROUND: This study aimed to explore the association between uric acid lowering and renal function. MATERIALS AND METHODS: We conducted a population-based cohort study with 1,534 subjects for 4 years from 2012 to 2016. The population was divided into four groups according to the interquartile range of changes in serum uric acid with quartile 1 representing lower quarter. Renal function decline was defined as eGFR decreased more than 10% from baseline in 2016. Renal function improvement was defined as eGFR increased more than 10% from baseline in 2016. Cox regression analysis was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: In the adjusted Cox regression models, compared to quartile 4, quartile 1 (HR = 0.64, 95% CI [0.49-0.85]), quartile 2 (HR = 0.65, 95% CI [0.50-0.84]) and quartile 3 (HR = 0.75, 95% CI [0.58-0.96]) have reduced risk of renal function decline. An increasing hazard ratio of renal function improvement was shown in quartile 1 (HR = 2.27, 95% CI [1.45-3.57]) and quartile 2 (HR = 1.78, 95% CI [1.17-2.69]) compared with quartile 4. CONCLUSIONS: Uric acid lowering is associated with changes in renal function. The management of serum uric acid should receive attention in clinical practice and is supposed to be part of the treatment of chronic kidney disease.

Association of metabolic syndrome with the incidence of low-grade albuminuria: a cohort study in middle-aged and elderly Chinese adults.

BACKGROUND: Individuals with metabolic syndrome have elevated risks of micro- and macro-albuminuria as well as chronic kidney disease (CKD). OBJECTIVE: To assess the influence of metabolic abnormalities on the presence of low-grade albuminuria (below the threshold for microalbuminuria). Design, participants, and main outcome measures: This community-based cohort study included 3,935 eligible individuals aged 40 years or older. The presence of low-grade albuminuria was detected in those without micro- or macro-albuminuria and analyzed according to the highest quartile of the baseline urinary albumin-to-creatinine ratio (ACR ≥11.13 mg/g). CKD was defined by an estimated glomerular filtration rate <60 mL/min/1.73 m2 or the new presence of albuminuria (ACR ≥30 mg/g). RESULTS: Overall, 577 (14.7%) participants developed low-grade albuminuria and 164 (4.2%) participants developed CKD during a mean follow-up period of 3.6 years. Compared with participants without metabolic syndrome, those with metabolic syndrome had greater risks of low-grade albuminuria [adjusted odd ratio (OR) and 95% confidence interval (95% CI): 1.30 (1.05-1.61)] and CKD [1.71 (1.20-2.44)]. Moreover, the incidence rates of low-grade albuminuria and CKD increased as the number of metabolic syndrome components increased (P for trend <0.0001). CONCLUSIONS: The presence of metabolic syndrome is associated with increased incidence rates of low-grade albuminuria and CKD the middle-aged and elderly Chinese populations.

Association of gonadal hormones and sex hormone binding globulin with risk of diabetes: A cohort study in middle-aged and elderly Chinese males.

AIM: Late-onset hypogonadism in men is related to the development of diabetes. The association of gonadal hormones, sex hormone binding globulin with diabetes has been studied in various studies. However, there is no cohort study on the relationship between gonadal hormone, sex hormone binding globulin and diabetes in Chinese. We aimed to provide an insight into the possible association in middle-aged and elderly Chinese males. METHODS: We included a population sample of 673 subjects aged 40 years or older. Total testosterone (TT), sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinising hormone (LH) were detected. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to estimate insulin sensitivity. Diabetes was diagnosed according to the 2010 American Diabetes Association criteria. RESULTS: With an average follow-up time of 3.2 ± 0.5 years, 9.8% of participants had developed diabetes. The prevalence of diabetes was decreased according to increasing SHBG quartiles (Q1:13.1%, Q2: 12.0%, Q3: 11.2%, Q4: 3.0%, P for trend < .0001) and TT (Q1:16.0%, Q2: 7.9%, Q3: 9.0%, Q4: 6.4%, P for trend < .0001). The ORs of diabetes for increasing SHBG quartiles were 4.52 (95% CI 1.40-14.57), 4.32 (95% CI 1.33-14.06), 3.89 (95% CI 1.21-12.50) and 1.00 (reference) respectively. But the odds of prevalent diabetes were not increased in different quartiles of TT, FSH and LH. In subgroup analyses, the relationship between SHBG and risk of incident diabetes was significantly increased in the population aged over 60, without insulin resistance and with eGFR < 90 mL/min per 1.73 m2 . CONCLUSIONS: Compared with gonadal hormones, a lower level of SHBG is independently associated with the risk of diabetes in middle-aged and elderly Chinese males.

Partial trisomy 9p and 14q microduplication in a patient with growth retardation: a case report and review of the literature.

Background Trisomy is a common chromosomal aberration, which usually presents with similar phenotypic abnormalities and developmental delay. Although defined as chromosome abnormalities with recognized symptoms including growth retardation, trisomy 9p and trisomy 14q have been rarely reported to occur at the same time. Case presentation Here, we describe a 16-year-old adolescent female affected by developmental delay and mild intellectual disability. She was confirmed to have both partial trisomy 9p (p24.3-p23) and 14q11.2 microduplication by chromosome microarray analysis (CMA). It is speculated that the extra chromosome in the patient may be a derivative 14 chromosome inherited from the parent after 3:1 disjunction during meiosis. The extra 9p segment proves to be pathogenic while the duplicated 14q11.2 remains indefinite. Conclusions Further studies are needed to assign the genes responsible for the developmental delay and craniofacial dysmorphisms and appoint dosage-sensitive genes of chromosome 9p.

Lipid accumulation product and late-onset hypogonadism in middle-aged and elderly men: results from a cross-sectional study in China.

OBJECTIVES: Hypogonadism in men is related to the deterioration of general health. However, the association between lipid overaccumulation and ageing-related hypogonadism remains an undetermined concept. We aimed to provide an insight into the possible links between the lipid accumulation product (LAP) and late-onset hypogonadism (LOH). SETTING: Sun Yat-sen Memorial Hospital of Sun Yat-sen University. PARTICIPANTS: We included a population sample of 997 subjects aged 40 years or older. PRIMARY AND SECONDARY OUTCOME MEASURES: The LAP was calculated by gender-specific equations using waist circumference (WC) and triglyceride (TG). LOH was defined by the presence of androgen deficiency symptoms and low serum total testosterone levels. RESULTS: The prevalence of LOH was 9.4% in this population and gradually increased according to increasing LAP quartiles. Compared with subjects without LOH, ageing men with LOH had higher body mass index, WC, systolic blood pressure, percentage of subjects currently smoking, TG and follicle stimulating hormone and lower low-density lipoprotein cholesterol and sex hormone binding globulin. In multivariate logistic regression analysis, the adjusted ORs of LOH for increasing LAP quartiles 1-4 were 1.00 (reference), 1.10 (95% CI 0.45-2.69), 2.15 (95% CI 0.93-4.94) and 3.83 (95% CI 1.73-8.45), respectively. CONCLUSION: Body lipid accumulation evaluated by the LAP is independently associated with the prevalence of LOH in middle-aged and elderly Chinese men.

Parity is associated with albuminuria and chronic kidney disease: a population-based study.

BACKGROUND AND AIMS: Epidemiological studies have shown that increasing parity is associated with risk of hypertension and diabetes in parous women. However, the relationship between the parity degree with chronic kidney disease (CKD) is still unknown. RESULTS: Parous women with higher parity had increased age, body mass index, waist circumference, systolic blood pressure, fasting plasma glucose, fasting insulin and decreased high-density lipoprotein cholesterol, eGFR and education levels. Compared with women with one-child birth, those with more than two-child births had greater prevalence of increased urinary albumin excretion (odds ratios [ORs] 1.53, 95% confidence intervals [CI], 1.03 - 2.28) and CKD (ORs 1.79, 95% CI, 1.24 - 2.58) after multiple adjustments. In dose-response analysis, a nonlinear relationship of parity degree with albuminuria and CKD was detected. CONCLUSION: Parity is associated with higher prevalence of albuminuria and CKD in middle-aged and elderly Chinese women. METHODS: We conducted a community-based study in 6,946 women to investigate the association of parity with albuminuria and CKD. Increased urinary albumin excretion was defined as albumin-to-creatinine ratio (ACR) greater or equal than 30 mg/g. CKD was defined as estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m² or presence of albuminuria.

Number of parity is associated with low-grade albuminuria in middle-aged and elderly Chinese women.

BACKGROUND: Women with a higher number of pregnancies have a higher risk of developing cardiovascular diseases. Subtle fluctuations in albumin excretion could be related to pathophysiologic changes in the vascular system. We aimed to investigate the possible association of parity with low-grade albuminuria. METHODS: We conducted a community-based study in 6495 women aged 40 years or older. Low-grade albuminuria was defined according to the highest quartile of urine albumin-to-creatinine ratio in participants free of micro- or macro-albuminuria. RESULTS: Parous women with a higher number of pregnancies had increased age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), fasting plasma glucose (FPG), and fasting insulin, as well as decreased high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR) levels, and proportion of menopause. The prevalence of low-grade albuminuria in parous women gradually increased with parity number. Compared with women with one childbirth, those with more than two childbirths were independently associated with a higher prevalent low-grade albuminuria (odds ratios [ORs] 1.41, 95% confidence interval [CI], 1.09-1.81) after multiple adjustments. In subgroup analysis after multiple adjustments, significant relation between parity number and prevalent low-grade albuminuria was detected in subjects age 55 years or older. CONCLUSION: Number of parity is associated with prevalent low-grade albuminuria in middle-aged and elderly Chinese women without micro- or macro-albuminuria.

Assessment of adiposity distribution and its association with diabetes and insulin resistance: a population-based study.

BACKGROUND: Rational measures in estimating adiposity distribution in diabetic patients has yet to be validated. This study aims to provide insight about the possible links between routinely available body adiposity parameters and the development of both diabetes and insulin resistance. METHODS: We performed a population-based cross-sectional study in 9496 subjects aged 40 years or older. All of the body adiposity measures including body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), waist-height ratio (WHtR), visceral adiposity index (VAI), body adiposity index (BAI) and lipid accumulation product index (LAP) were separately evaluated according to standard measurement methods. Diabetes was diagnosed according to the American Diabetes Association 2010 criteria. RESULTS: All tested body adiposity measurements were significantly associated with fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) 2 h glucose, HbA1c and fasting insulin. Compared with other adiposity phenotypes, LAP have shown the relatively strongest while BAI have shown the relatively weakest association with increased odds of both diabetes and insulin resistance across all logistic regression models. Additionally, LAP provided the best discrimination accuracy for diabetes [area under the curve (AUC): 0.658 95% confidence intervals (CI) 0.645-0.671] and insulin resistance (AUC: 0.781 95% CI 0.771-0.792) when compared with other body adiposity parameters. CONCLUSIONS: The LAP index seems to be a better indicator than other adiposity measures tested in the study to evaluate the association of visceral fat mass with diabetes and insulin resistance, which should be given more consideration in the clinical practice.

Association of Serum Retinol-Binding Protein 4 Levels and the Risk of Incident Type 2 Diabetes in Subjects With Prediabetes.

OBJECTIVE: To explore the association of serum retinol-binding protein 4 (RBP4) levels and risk for the development of type 2 diabetes in individuals with prediabetes. RESEARCH DESIGN AND METHODS: A population-based prospective study was conducted among 1,011 Chinese participants with prediabetes (average age 55.6 ± 7.2 years). Incident type 2 diabetes was diagnosed according to the American Diabetes Association 2010 criteria. Serum RBP4 levels were measured using a commercially available ELISA. We analyzed the association of serum RBP4 levels with the risk of incident type 2 diabetes using the Cox proportional hazards model. RESULTS: During a median follow-up period of 3.1 years, 153 participants developed incident type 2 diabetes. A U-shaped association was observed between serum RBP4 levels and the risk of incident type 2 diabetes, with the lowest risk in the RBP4 range of 31-55 µg/mL. Multivariate Cox regression model analysis showed that serum RBP4 levels <31 µg/mL and RBP4 levels >55 µg/mL were associated with an increased risk of incident type 2 diabetes. The adjusted hazard ratios (95% CI) were 2.01 (1.31-3.09) and 1.97 (1.32-2.93), respectively, after adjusting for age, sex, BMI, waist circumference, γ-glutamyltransferase, HOMA of insulin resistance index, fasting plasma glucose, 2-h plasma glucose, and glycated hemoglobin (HbA1c) levels. CONCLUSIONS: A U-shaped relationship exists between serum RBP4 levels and the risk of incident type 2 diabetes in subjects with prediabetes.

Visceral adiposity index is associated with increased urinary albumin excretion: A population-based study.

BACKGROUND: The effects of visceral fat accumulation on the renal damage have drawn much attention. We aimed to investigate the possible relationship between visceral adiposity and albuminuria. METHODS: We included information from a population-based study in 9473 subjects aged 40 years or older. As a novel and valid indicator for visceral adipose function, visceral adiposity index (VAI) was determined by gender-specific equations and calculated using simple anthropometric and functional parameters. Increased urinary albumin excretion was defined as albumin-to-creatinine ratio (ACR) 30 mg/g or greater. RESULTS: The prevalence rate of increased urinary albumin excretion was 6.6% in this population and gradually increased across VAI quartiles. Participants with higher VAI had elevated age, blood pressure, cholesterol, fasting insulin and decreased high density lipoprotein cholesterol and estimated glomerular filtration rate (eGFR) level. In multivariate logistic regression analysis, the adjusted odds ratios (ORs) of increased urinary albumin excretion for increasing VAI quartiles were 1.00 (reference), 1.29 (95% confidence intervals [CI] 0.94-1.76), 1.46 (95% CI 1.08-1.97) and 1.79 (95% CI 1.33-2.41). In subgroup analysis and after multiple adjustments, significant relation between VAI level and prevalent increased urinary albumin excretion was detected in women, younger subjects, non-obesity subjects, those without diabetes and those with eGFR ≥60 ml/min per 1.73 m2. CONCLUSION: Visceral fat accumulation evaluating by VAI is independently associated with increased urinary albumin excretion in middle-aged and elderly Chinese.