Xinrong Zhou

Circulating Betatrophin Levels Are Increased in Patients With Type 2 Diabetes and Associated With Insulin Resistance

CONTEXT Betatrophin has recently attracted increasing interests as a potential β-cell regenerative therapy in diabetes. However, differences in betatrophin profiles in patients with type 2 diabetes mellitus (T2DM) remain unclear. OBJECTIVE The objective of the study was to examine circulating betatrophin levels in subjects with different glucose tolerance status and its correlation with insulin resistance. DESIGN, SETTING, AND PARTICIPANTS Serum betatrophin levels were measured using an ELISA in age-, sex-, body mass index-, and blood lipid-matched subjects with normal glucose tolerance (n = 137), isolated impaired fasting glucose (n = 69), isolated impaired glucose tolerance (n = 120), and newly diagnosed T2DM (n = 112) from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal study. RESULTS Serum betatrophin levels were elevated in patients with T2DM compared with subjects with normal glucose tolerance, isolated impaired fasting glucose, or isolated impaired glucose tolerance (798.6 ± 42.5 vs 692.7 ± 29.0, P < .05, vs 682.7 ± 43.0, P < .05, vs 646.8 ± 34.3 pg/mL, P < .01). Betatrophin levels positively correlated with the index of homeostasis model assessment of insulin resistance (partial r = 0.11); inversely correlated with quantitative insulin sensitivity check index (partial r = -0.11), the Gutt insulin sensitivity index (partial r = -0.12), and the Matsuda insulin sensitivity index (partial r = -0.11) after controlling for age, sex, body mass index, and blood lipid in all participants (all values of P < .05). CONCLUSION Circulating betatrophin levels are increased in patients with T2DM and associated with indexes of insulin resistance.

Clinical usefulness of lipid ratios, visceral adiposity indicators, and the triglycerides and glucose index as risk markers of insulin resistance

BackgroundTo directly compare traditional lipid ratios (total cholesterol [TC]/high density lipoprotein cholesterol [HDL-C], non-HDL-C/HDL-C, low density lipoprotein cholesterol [LDL-C]/HDL-C, and triglycerides [TG]/HDL-C), apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio, visceral adiposity index (VAI), lipid accumulation product (LAP), and the product of TG and fasting glucose (TyG) for strength and independence as risk factors for insulin resistance (IR).MethodsWe conducted a cross-sectional analysis of 7629 Chinese adults using data from the China Health and Nutrition Survey 2009.ResultsFor all lipid ratios (traditional lipid ratios and apoB/apoA-I), among both sexes, TG/HDL-C explained the most additional percentage of variation in HOMA-IR (2.9% in men, and 2.3% in women); for all variables of interest, the variability in HOMA-IR explained by VAI and TG/HDL-C were comparable; TyG had the most significant association with HOMA-IR, which explained 9.1% for men and 7.8% for women of the variability in HOMA-IR. Logistic regression analysis showed the similar patterns. Receiver operating characteristic (ROC) curve analysis showed that, among both sexes, TG/HDL-C was a better discriminator of IR than apoB/apoA-I; the area under the ROC curve (AUC) for VAI (0.695 in men and 0.682 in women) was greater than that for TG/HDL-C (AUC 0.665 in men and 0.664 in women); TyG presented the greatest value of AUC (0.709 in men and 0.711 in women).ConclusionThe apoB/apoA-I performs no better than any of the traditional lipid ratios in correlating with IR. The TG/HDL-C, VAI and TyG are better markers for early identification of IR individuals.

Lipid phenotypes in patients with nonalcoholic fatty liver disease

OBJECTIVE There has been conflicting evidence regarding the role of single lipid species in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to explore the associations between dyslipidemia phenotypes (combinations of lipid parameters) and the risk of NAFLD. METHODS We conducted a cross-sectional analysis using a cohort of 9560 apparently healthy Chinese adults who underwent comprehensive health checkups including abdominal ultrasonography. RESULTS Of 3709 participants with NAFLD, 41.8% were classified as normolipemia (NL), 3.8% as combined hyperlipidemia, 3.2% as hypercholesterolemia, 17.7% as dyslipidemia of metabolic syndrome (MetS), 10.2% as isolated low high-density lipoprotein cholesterol (HDL-C), and 23.3% as isolated hypertriglyceridemia. The multivariable-adjusted odds ratios (ORs) (with 95% confidence intervals) for NAFLD in those with combined hyperlipidemia, those with hypercholesterolemia, those with MetS dyslipidemia, those with low HDL-C, and those with hypertriglyceridemia compared with those with NL were 4.79 (3.19-7.20), 1.26 (0.94-1.69), 3.31 (2.74-3.99), 1.13 (0.95-1.34), and 2.63 (2.26-3.08), respectively. The associations between combined hyperlipidemia, MetS dyslipidemia, or hypertriglyceridemia and risk of NAFLD were consistently seen in various evaluated subgroups. The interactions between lipid phenotypes and sex, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), or uric acid (UA) were not significant for NAFLD (all P>0.05). CONCLUSIONS There were diverse dyslipidemia phenotypes in patients with NAFLD. Combined hyperlipidemia, MetS dyslipidemia, and hypertriglyceridemia were strongly and independently associated with increased risk of NAFLD. Gender, BMI, BP, FPG, and UA status did not modify the associations between dyslipidemia phenotypes and NAFLD.

Short-Term Effects of Continuous Subcutaneous Insulin Infusion Therapy in Perioperative Patients with Diabetes Mellitus

BACKGROUND Hyperglycemia is common and hard to control in surgical patients with diabetes. We retrospectively investigated short-term effects of continuous subcutaneous insulin infusion (CSII) in perioperative patients with diabetes. PATIENTS AND METHODS Perioperative patients with diabetes discharged between January 1, 2006 and January 1, 2012 were included. Glucose control and postoperative outcomes were compared between the patients using CSII or non-CSII insulin therapy. RESULTS We identified 108 pairs of patients matched by propensity and surgical category who were using CSII therapy (CSII group) or non-CSII insulin therapy (control group). The CSII group had significantly lower fasting glucose levels (on the first postoperative day, 9.06±3.09 mmol/L vs. 11.05±4.19 mmol/L; P=0.003) and lower mean glucose levels (on the operation day, 9.93±2.65 mmol/L vs. 12.05±3.86 mmol/L; P=0.001). The CSII group also had a lower incidence of fever (on the first postoperative day, 30.4% vs. 53.2%; P=0.005). Furthermore, patients in the CSII group experienced significantly shorter postoperative intervals for suture removal (P=0.02) and hospital discharge (P=0.03). No significant difference in the total medical expenditure was observed between the two groups (P=0.47). We also made a comparison between the 30 pairs of patients who were using CSII or multiple daily insulin injection therapy but observed no significant difference between these two therapies in glucose control or postoperative outcomes. CONCLUSIONS Compared with non-CSII insulin therapy, even short-term implementation of CSII can improve the postoperative control of glucose, reduce the incidence of postoperative fever, and shorten the time for suture removal and discharge in surgical patients with diabetes.

Insulin upregulates betatrophin expression via PI3K/Akt pathway

Betatrophin is regarded as a liver-produced hormone induced by insulin resistance (IR). However, it remains largely unknown how IR regulates betatrophin expression. To study whether IR could regulate betatrophin expression and the corresponding molecular mechanisms, betatrophin levels were examined in 6 in vitro IR models which were established using human hepatocytes L02 with different agents, including tumor necrosis factor-α, interleukin-1β, dexamethasone, palmitate, high glucose and insulin and betatrophin levels were elevated only in the insulin group. These results suggest that it is insulin, not IR that promotes betatrophin expression. In the meantime, PI3K/Akt pathway was activated by insulin and suppressed by above agents that caused IR. Insulin-upregulated betatrophin expression was suppressed by PI3K/Akt inhibitors and IR, suggesting that insulin upregulates and IR decreases betatrophin production through PI3K/Akt pathway. Consistently, the treatment of insulin in mice dose-dependently upregulated betatrophin levels, and the administration of metformin in IR mice also stimulated betatrophin production since published study showed metformin improved PI3K/Akt pathway and IR. In humans, compared with those without insulin treatment, serum betatrophin levels were increased in type 2 diabetic patients with insulin treatment. In conclusion, insulin stimulates betatrophin secretion through PI3K/Akt pathway and IR may play an opposite role.

Correlation of liver enzymes with diabetes and pre-diabetes in middle-aged rural population in China

The survey aimed to explore the association of liver transaminases with the prevalence of type 2 diabetes mellitus (T2DM) and pre-diabetes (pre-DM) in the middle-aged rural population in China. A cross-sectional study was conducted in 10 800 middle-aged subjects who lived in rural area of central China. The 75-g oral glucose-tolerance test (OGTT) was performed. Participants were asked to complete physical examination and standard questionnaire. The serum liver transaminases (ALT and GGT), HbA1C and serum lipids were measured. In middle-aged rural population, the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), impaired fasting glucose combined with impaired glucose tolerance (IFG+IGT) and DM was 4.0%, 11.8%, 2.6% and 10.0%, respectively. Some measurements were higher in males than in females, such as waist hip ratio (WHR), blood pressure, fasting blood glucose (FBG), high density lipoprotein-cholesterol (HDL-C), and liver enzymes (ALT and GGT). Further, we found that elevated serum GGT and ALT levels were significantly positively correlated with the prevalence of DM, independent of central obesity, serum lipid and insulin resistance (IR) in both genders. However, the correlation of GGT and ALT with pre-DM was determined by genders and characteristics of liver enzymes. Higher serum GGT was indicative of IGT in both genders. The association of serum ALT with pre-DM was significant only in female IGT group. In conclusion, our present survey shows both serum GGT and ALT are positively associated with DM, independent of the cardiovascular risk factors in both genders.SummaryThe survey aimed to explore the association of liver transaminases with the prevalence of type 2 diabetes mellitus (T2DM) and pre-diabetes (pre-DM) in the middle-aged rural population in China. A cross-sectional study was conducted in 10 800 middle-aged subjects who lived in rural area of central China. The 75-g oral glucose-tolerance test (OGTT) was performed. Participants were asked to complete physical examination and standard questionnaire. The serum liver transaminases (ALT and GGT), HbA1C and serum lipids were measured. In middle-aged rural population, the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), impaired fasting glucose combined with impaired glucose tolerance (IFG+IGT) and DM was 4.0%, 11.8%, 2.6% and 10.0%, respectively. Some measurements were higher in males than in females, such as waist hip ratio (WHR), blood pressure, fasting blood glucose (FBG), high density lipoprotein-cholesterol (HDL-C), and liver enzymes (ALT and GGT). Further, we found that elevated serum GGT and ALT levels were significantly positively correlated with the prevalence of DM, independent of central obesity, serum lipid and insulin resistance (IR) in both genders. However, the correlation of GGT and ALT with pre-DM was determined by genders and characteristics of liver enzymes. Higher serum GGT was indicative of IGT in both genders. The association of serum ALT with pre-DM was significant only in female IGT group. In conclusion, our present survey shows both serum GGT and ALT are positively associated with DM, independent of the cardiovascular risk factors in both genders.

Sex differences in the effect of HbA1c-defined diabetes on a wide range of cardiovascular disease risk factors

Abstract Objective Sex differences in the association of HbA1c and cardiovascular disease (CVD) risk remain controversial. We examined CVD risk profile in both HbA1c-defined diabetic and nondiabetic men and women. Methods We conducted a cross-sectional analysis of 7139 Chinese adults using data from the China Health and Nutrition Survey 2009. Results HbA1c-defined nondiabetic men have a more favorable CVD risk profile than female counterparts. However, HbA1c-defined diabetic men have higher levels of triglyceride, low-density lipoprotein (LDL)-cholesterol, and triglyceride/high-density lipoprotein (HDL)-cholesterol and lower levels of HDL-cholesterol, be more visceral obese as indicated by visceral adiposity index (VAI) and lipid accumulation product (LAP), and more insulin resistant as assessed by the triglycerides and glucose index (TyG) than HbA1c-defined diabetic women. Furthermore, HbA1c-defined diabetic men showed greater relative differences in ferritin than diabetic women when compared with their nondiabetic counterparts. Statistically significant sex by HbA1c-defined diabetes status interactions were observed for triglyceride, LDL-cholesterol, HDL-cholesterol, triglyceride/HDL cholesterol, VAI, LAP, TyG, and ferritin (all ps < 0.05). Consideration of VAI or homeostasis model assessment of insulin resistance or both failed to eliminate the sex differences in the associations between diabetes and these CVD risk factors. Conclusions Men who progressed from HbA1c-defined nondiabetes to HbA1c-defined diabetes have greater metabolic deteriorations and put on more visceral adiposity than women. Key messages HbA1c-defined nondiabetic men have a more favorable CVD risk profile than female counterparts. Men have to undergo a greater metabolic deterioration to develop HbA1c-defined diabetes than do women. Men have to put on more visceral adiposity to develop HbA1c-defined diabetes than do women.

Profile and clinical implication of circular RNAs in human papillary thyroid carcinoma

Background Differently expressed circular RNAs (circRNAs) have been reported to play a considerable role in tumor behavior; however, the expression profile and biological function of circRNAs in papillary thyroid carcinoma (PTC) remains unknown. Thus, the study was aimed to characterize the circRNA expression profile to comprehensively understand the biological behavior of PTC. Methods We investigated the expression profile of circRNAs using circRNA microarray in three pairs of PTC and adjacent normal tissues. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate eight candidate circRNAs in 40 paired PTC tumors and adjacent normal samples. Next, we employed a bioinformatics tool to identify putative miRNA and circRNA-associated downstream genes, followed by constructing a network map of circRNA-miRNA-mRNA interactions and exploring the potential role of the candidate circRNAs. Results In total, 206 up- and 177 downregulated circRNAs were identified in PTC tissues (fold change >1.5; P < 0.05). The expression levels of eight candidate circRNAs confirmed by qRT-PCR were significantly different between the PTC and normal samples. The downstream genes of candidate circRNAs participated in various biological processes and signaling pathways. The most up and downregulated circRNAs were hsa_circRNA_007148 and hsa_circRNA_047771. The lower expression level of hsa_circRNA_047771 was associated BRAFV600 mutation, lymph node metastasis (LNM), as well as with advanced TNM stage (all P < 0.05). The higher expression level of hsa_circRNA_007148 was significantly correlated with LNM (P < 0.05). The areas under receiver operating curve were 0.876 (95% CI [0.78–0.94]) for hsa_circRNA_047771 and 0.846 (95% CI [0.75–0.96]) for hsa_circRNA_007148. Discussion The study suggests that dysregulated circRNAs play a critical role in PTC pathogenesis. PTC-related hsa_circRNA_047771 and hsa_circRNA_007148 may serve as potential diagnostic biomarkers and prognostic predictors for PTC patients.

Glycemic index, glycemic load, and glycemic response to pomelo in patients with type 2 diabetes

Food intake has a great influence on blood glucose in patients with diabetes. This study was to determine the glycemic index (GI) and glycemic load (GL) of a particular pomelo named Majia pomelo and its effects on postprandial glucose (PPG) in patients with type 2 diabetes (T2D). Twenty healthy subjects and 20 T2D patients (controlled on lifestyle measures and/or metformin) were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement. To test effects of Majia pomelo on PPG, 19 hospitalized T2D patients (controlled on insulin therapy) were selected for a 9-day study. The dose of insulin for each patient was adjusted on the first 3 days. A total of 100 mg Majia pomelo was consumed per meal in the last 3 tested days. Blood glucose was measured to evaluate the glycemic excursions. The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34±1.88 and 72.15±1.95 respectively. The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo, indicting Majia pomelo as a high GI but low GL fruit. Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation. It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients. These results may mean more varieties of food choices for T2D patients.SummaryFood intake has a great influence on blood glucose in patients with diabetes. This study was to determine the glycemic index (GI) and glycemic load (GL) of a particular pomelo named Majia pomelo and its effects on postprandial glucose (PPG) in patients with type 2 diabetes (T2D). Twenty healthy subjects and 20 T2D patients (controlled on lifestyle measures and/or metformin) were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement. To test effects of Majia pomelo on PPG, 19 hospitalized T2D patients (controlled on insulin therapy) were selected for a 9-day study. The dose of insulin for each patient was adjusted on the first 3 days. A total of 100 mg Majia pomelo was consumed per meal in the last 3 tested days. Blood glucose was measured to evaluate the glycemic excursions. The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34±1.88 and 72.15±1.95 respectively. The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo, indicting Majia pomelo as a high GI but low GL fruit. Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation. It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients. These results may mean more varieties of food choices for T2D patients.