Yingli Lu

Increased risk of bladder cancer with pioglitazone therapy in patients with diabetes: A meta-analysis

AIMS Emerging studies suggest a possible increased risk of bladder cancer with pioglitazone therapy. We therefore pooled data available to examine the association between pioglitazone therapy and bladder cancer in patients with diabetes. METHODS We searched Medline and Embase to identify studies that reported the effect of pioglitazone on bladder cancer among diabetic patients. Summary effect estimates were derived using a fixed-effects meta-analysis model. RESULTS Five studies included 2,350,908 diabetic patients. Pioglitazone was associated with a significantly higher risk of bladder cancer (relative risk [RR] 1.17, 95% confidence interval (CI) 1.03-1.32, P=0.013). No relation between pioglitazone and bladder cancer was found for duration of therapy <12 months and cumulative dose <28,000 mg. The RR for bladder cancer in subjects with 12-24 months of pioglitazone use was 1.34 (95% CI 1.08-1.66, P=0.008). The effect was even stronger for cumulative treatment duration >24 months (RR 1.38, 95% CI 1.12-1.70, P=0.003). There was a significant risk for patients with cumulative dose >28,000 mg (RR 1.58, 95% CI 1.12-2.06, P=0.001). CONCLUSIONS Pioglitazone treatment appears to be associated with a significantly increased risk of bladder cancer in patients with diabetes.

Is Exposure to Famine in Childhood and Economic Development in Adulthood Associated With Diabetes

CONTEXT The Chinese were afflicted by great famine between 1959 and 1962. These people then experienced rapid economic development during which the gross domestic product per capita increased from

Diabetes Mellitus and Risk of Bladder Cancer: A Meta-Analysis of Cohort Studies

28 in 1978 to

Risk of bladder cancer in patients with diabetes mellitus: an updated meta-analysis of 36 observational studies

6807 in 2013. We hypothesize that these two events are associated with the booming rate of diabetes in China. OBJECTIVE We aimed to explore whether exposure to famine in early life and high economic status in adulthood was associated with diabetes in later life. DESIGN AND SETTING Our data of 6897 adults were from a cross-sectional Survey on Prevalence in East China for Metabolic Diseases and Risk Factors study in 2014. Among them, 3844 adults experienced famine during different life stages and then lived in areas with different economic statuses in adulthood. MAIN OUTCOME MEASURE Diabetes was considered as fasting plasma glucose of 7.0 mmol/L or greater, hemoglobin A1c of 6.5% or greater, and/or a previous diagnosis by health care professionals. RESULTS Compared with nonexposed subjects, famine exposure during the fetal period (odds ratio [OR]1.53, 95% confidence interval [CI]1.09-2.14) and childhood (OR 1.82, 95% CI 1.21-2.73) was associated with diabetes after adjusting for age and gender. Further adjustments for adiposity, height, the lipid profile, and blood pressure did not significantly attenuate this association. Subjects living in areas with high economic status had a greater diabetes risk in adulthood (OR 1.46, 95% CI 1.20-1.78). In gender-specific analyses, fetal-exposed men (OR 1.64, 95% CI, 1.04-2.59) and childhood-exposed women (OR 2.81, 95% CI, 1.59-4.97) had significantly greater risk of diabetes. CONCLUSIONS The rapid increase in the prevalence of diabetes in middle-aged and elderly people in China is associated with the combination of exposure to famine during the fetal stage and childhood and high economic status in adulthood. Our findings may partly explain the booming diabetes phenomenon in China.

Exposure to Famine in Early Life and Nonalcoholic Fatty Liver Disease in Adulthood.

Background Increasing evidence suggests that diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. To provide a quantitative assessment of this association, we evaluated the relation between DM and incidence and mortality of bladder cancer in an updated meta-analysis of cohort studies. Methods We identified cohort studies by searching the EMBASE and MEDLINE databases, through 31 March 2012. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with random-effects models. Results A total of 29 cohort studies (27 articles) were included in this meta-analysis. DM was associated with an increased incidence of bladder cancer (RR 1.29, 95% CI: 1.08–1.54), with significant evidence of heterogeneity among these studies (p<0.001, I2 = 94.9%). In stratified analysis, the RRs of bladder cancer were 1.36 (1.05–1.77) for diabetic men and 1.28 (0.75–2.19) for diabetic women, respectively. DM was also positively associated with bladder cancer mortality (RR 1.33, 95% CI: 1.14–1.55), with evident heterogeneity between studies (p = 0.002, I2 = 63.3%). The positive association was observed for both men (RR 1.54, 95% CI: 1.30–1.82) and women (RR 1.50, 95% CI: 1.05–2.14). Conclusion These findings suggest that compared to non-diabetic individuals, diabetic individuals have an increased incidence and mortality of bladder cancer.

Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

BackgroundIncreasing evidence suggests that a history of diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. We performed a systematic review with meta-analysis to explore this relationship.MethodsWe identified studies by a literature search of Medline (from 1 January 1966) and EMBASE (from 1 January 1974), through 29 February 2012, and by searching the reference lists of pertinent articles. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated with a random-effects model.ResultsA total of 36 studies (9 case–control studies, 19 cohort studies and 8 cohort studies of patients with diabetes) fulfilled the inclusion criteria. Analysis of all studies showed that DM was associated with an increased risk of bladder cancer (the summary RR = 1.35, 95% CI 1.17–1.56, p < 0.001, I2 = 94.7%). In analysis stratified by study design, diabetes was positively associated with risk of bladder cancer in case–control studies (RR = 1.45, 95% CI 1.13-1.86, p = 0.005, I2 = 63.8%) and cohort studies (RR = 1.35, 95% CI 1.12-1.62, p < 0.001, I2 = 94.3%), but not in cohort studies of diabetic patients (RR = 1.25, 95% CI 0.86–1.81, p < 0.001, I2 = 97.4%). The RRs of bladder cancer were 1.38 (1.08-1.78) for men and 1.38 (0.90-2.10) for women with diabetes, respectively. Noteworthy, the relative risk of bladder cancer was negatively correlated with the duration of DM, with the higher risk of bladder cancer found among patients diagnosed within less than 5 years.ConclusionsThese findings support the hypothesis that men with diabetes have a modestly increased risk of bladder cancer, while women with diabetes were not the case.

The GLP-1 Analogue Exenatide Improves Hepatic and Muscle Insulin Sensitivity in Diabetic Rats: Tracer Studies in the Basal State and during Hyperinsulinemic-Euglycemic Clamp

CONTEXT Epidemiologic studies have indicated that early life nutrition influences later risk of obesity, type 2 diabetes, and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is also considered a metabolic disease. OBJECTIVE The aim was to explore the association between adult NAFLD and fetal or childhood exposure to Great Chinese Famine between 1959 and 1962 during fetal and childhood period. DESIGN AND SETTING In total, 5306 subjects from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors study were divided into a fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/young adult-exposed (1921-1948), and nonexposed (1963-1974, reference) group. MAIN OUTCOME MEASURE The degrees of steatosis of NAFLD were determined by ultrasonography. RESULTS The prevalences of NAFLD in the nonexposed (1963-1974), fetal-exposed, and childhood-exposed participants were 55.9%, 55.8%, and 55.4% in men and 33.0%, 46.3%, and 51.7% in women, respectively. Compared with those nonexposed, fetal- and childhood-exposed women but not men had a significantly higher prevalence of moderate-severe steatosis (P < .05). A significant association existed in women between increased alanine aminotransferase and both fetal and childhood exposure to famine, after adjusting for age, rural/urban residence, economic status, body mass index, diabetes, dyslipidemia, and hypertension (both P < .05). Famine exposure during the fetal period (odds ratio 1.77, 95% confidence interval 1.22, 2.57) and childhood (odds ratio 1.82, 95% confidence interval 1.35, 2.46) was associated with an increased prevalence of moderate-severe NAFLD in women in the above fully adjusted model. CONCLUSIONS Exposure to the Great Famine in early life had sex-specific association with moderate-severe NAFLD. This indicates that malnutrition in early life may influence the development of adult NAFLD; thus pregnant women and their infants and children may require the highest priority in obtaining nutritional relief.

Acute effects of different glycemic index diets on serum motilin, orexin and neuropeptide Y concentrations in healthy individuals

BackgroundThere is a high prevalence of diabetes mellitus (DM) and dyslipidemia in women with polycystic ovary syndrome (PCOS). The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet.MethodsFemale Sprague-Dawley rats were divided into 3 groups: the control group(C), n = 10; the andronate-treated group (Andronate), n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks); and the andronate-treated and high-fat diet group (Andronate+HFD), n = 10. The rate of glucose appearance (Ra of glucose), gluconeogenesis (GNG), and the rate of glycerol appearance (Ra of glycerol) were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured.ResultsCompared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P < 0.05) but similar blood glucose concentrations. Of the two andronate-treated groups, the andronate+HFD group had the most serious insulin resistance (IR). Estrus cycles were completely acyclic, with polycystic ovaries and elevated serum lipid profiles in the andronate+HFD group (P < 0.05). Ra of glucose and GNG increased significantly in the andronate+HFD rats. However, the Ra of glycerol was similar in the three groups.ConclusionsAndronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS.

Peripheral endomorphin-1 levels are suppressed in diabetic patients

Objective. Glucagon-like peptide-1 (GLP-1) analogues (e.g., exenatide) increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues. Methods. Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C); nondiabetic + exenatide (C + E); diabetic (D); diabetic + exenatide (D + E) with diabetes induced by streptozotocin and high fat diet. Infusion of 3-3H-glucose and U-13C-glycerol was used to measure basal rates of appearance (Ra) of glucose and glycerol and gluconeogenesis from glycerol (GNG). During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-14C-glucose. Results. In the diabetic rats, exenatide reduced the basal Ra of glucose (P < 0.01) and glycerol (P < 0.01) and GNG (P < 0.001). During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P < 0.01) during the clamp. In the nondiabetic rats, exenatide had no effect. Conclusion. In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.

Rosiglitazone protects diabetic rats from liver destruction

AIM To determine whether different glycemic index (GI) diets have different effects on the acute secretion of motilin, orexin and neuropeptide Y (NPY), regulators of food intake, energy homeostasis and glucose metabolism. METHODS Fifty healthy volunteers were randomly assigned to two groups and were fed an isocaloric breakfast (464 kcal) containing high GI (HGI; GI=90) or low GI (LGI; GI=47) components. Serum motilin, orexin, and NPY concentrations were measured before (0 h) and 2h after the meal. RESULTS The concentrations of motilin, orexin-A, NPY, C-peptide, and blood glucose at 0 h were similar in both groups of subjects. However, 2 h after breakfast, the serum motilin, NPY, C-peptide, and blood glucose concentrations were increased and orexin-A concentrations were decreased in both groups. The percentage changes from 0 to 2 h [(2-h value-0-h value)/baseline×100)] in motilin (27.72±2.46% vs. 20.95±2.06%, p=0.04) and orexin-A (9.15±2.06% vs. 3.49±1.67%, p=0.038) concentrations were significantly higher in the LGI group than in the HGI group. By contrast, the percentage changes in NPY (53.7±9.73% vs. 28.1±5.2%, p=0.026) and blood glucose (12.3±3.78% vs. 1.77±2.52%, p=0.025) concentrations were significantly greater in the HGI group than in the LGI group. Although C-peptide concentrations increased significantly after breakfast in both groups, the magnitude of the increase was similar (132.69±25.15% vs. 139.98±27.29%, p=0.845). Motilin and NPY concentrations were moderately positive correlated (r=0.410, p=0.042), while orexin-A and NPY concentrations were negatively correlated (r=-0.429, p=0.033) at 2h in the LGI group. CONCLUSIONS A breakfast with a LGI reduced the secretion of orexin-A but significantly stimulated motilin secretion, without marked effects on the secretion of NPY. Therefore, consumption of a LGI diet may help to regulate food intake and energy expenditure in healthy individuals based on the changes in these hormones.