Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.

OBJECTIVE: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. METHODS: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. RESULTS: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). CONCLUSION: An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Prevalence of dyslipidemia and its control in type 2 diabetes: A multicenter study in endocrinology clinics of China.

OBJECTIVE: The aim of this study was to assess the levels of serum lipid and awareness, treatment, and control of dyslipidemia in type 2 diabetes mellitus (T2DM) patients from top-ranked endocrinology clinics in large cities of China. MATERIALS AND METHODS: A cross-sectional study in a representative sample of 4807 Chinese adults 40 to 75 years of age was conducted during 2010 to 2011 at 20 endocrinology clinics in top-ranked hospitals covering most of the major cities of China. Serum lipid levels were measured, and treatment of dyslipidemia was recorded and assessed. RESULTS: In the present study, the prevalence of dyslipidemia was 67.1% in T2DM subjects. Among those with dyslipidemia, the proportion of awareness and treatment was 68.7% and 55.9%. Among participants with lipid-lowering therapy, 686 subjects achieved the low-density lipoprotein cholesterol (LDL-C) control less than 2.60 mmol/L, with the rate being 39.4%. In those patients with previous cardiovascular disease, the percentage of participants who achieved LDL-C goal (1.80 mmol/L) was 15.3%. CONCLUSION: The prevalence of dyslipidemia is high, and the awareness, treatment, and control of dyslipidemia are relatively low in Chinese T2DM patients. This calls for the awareness and intervention of dyslipidemia in these patients.

Association of cytotoxic T-lymphocyte associated antigen 4 gene polymorphism with type 1 diabetes mellitus: a meta-analysis.

To evaluate the association between costimulatory molecule cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene polymorphism and type 1 diabetes mellitus(T1DM), sixty-three published studies before December, 2011 were included. Meta-analysis was performed for each genotype in a random/fixed effect model. The combined odds ratio (OR) with 95% confidence interval (95%CI) was calculated to estimate the strength of the association. Overall, significant correlation was noted between CTLA-4 gene polymorphism (i.e. +49A/G, CT60A/G in a per-allele model) and the risk of T1DM (for +49A/G: OR=1.47, 95%CI=1.36-1.60, P<0.001; for CT60A/G: OR=1.31, 95%CI=1.18-1.45, P<0.001). However, no significant association was noted between C(-318)T polymorphism and T1DM. In the subgroup analysis, for +49A/G and CT60A/G, the statistically significant associations were also demonstrated in diverse racial descents (Caucasian and Asian) and age of onset (<20 years and >20 years). In conclusion, our results suggest that CTLA-4 polymorphism contributes to the susceptibility of T1DM.

Association of plasma total and high-molecular-weight adiponectin with risk of colorectal cancer: an observational study in Chinese male.

The research is to investigate the association between plasma concentrations of total and high-molecular-weight (HMW) adiponectin and risk of early and advanced colorectal cancer. One hundred and sixty-five male colorectal cancer patients and one hundred and two controls were enrolled; based on the T factor of the TNM system, intraepithelial carcinoma and submucosally invasive carcinoma were defined as early cancer, and invasion into the muscularis propria or deeper was defined as advanced cancer. The plasma levels of glucose, fasting insulin, total cholesterol, triglyceride, and total and HMW adiponectin levels were measured. Each factor level was designated as low or high, and the risk of cancer was estimated by univariate and multivariate logistic regression analyses. In the patients with early cancer, high waist/hip ratio (WHR), high fasting insulin, high HOMA model insulin resistance index (HOMA-IR), low total adiponectin and HMW adiponectin were all associated with a significant increase in the odds ratio (OR) by univariate analysis. In multivariate analysis, WHR, HOMA-IR, total adiponectin and HMW adiponectin were all related to increased cancer risk. However, in the patients with advanced cancer, only low HMW adiponectin was associated with a significant increase in the OR by univariate analysis. In multivariate analysis, a low HMW adiponectin level was still related to increased cancer risk, with an adjusted OR of 3.971 (P = 0.036). In conclusion, a decreased level of adiponectin was a strong risk factor not only for early colorectal cancer but also for advanced colorectal in Chinese male patients. HMW adiponectin might be more closely associated with colorectal cancer risk than total adiponectin.

Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with polycystic ovary syndrome: a meta-analysis.

The association between Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma (PPAR) and polycystic ovary syndrome (PCOS) has been investigated in several studies, whereas results were often incompatible. We conducted a meta-analysis to evaluate the association of Pro12Ala polymorphism in PPAR with PCOS susceptibility. A meta-analysis was performed on the published studies before November, 2011. Meta-analysis was performed for genotypes CG versus CC, CG+GG versus CC and G allele versus C allele in a fixed effect model. The combined odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to estimate the strength of the association. A total of 13 studies including 1,598 cases and 1,881 controls were enrolled. Ultimately, sensitivity analysis demonstrated that, in total, there was no significant association between Pro12Ala polymorphism and PCOS in the contrast of G allele versus C allele OR = 0.84 (95 % CI 0.69-1.04) and in Europeans, no significant association in the comparison of G allele versus C allele (OR = 0.84, 95 % CI 0.67-1.06) was also indicated. In summary, according to the results of our meta-analysis, strictly, the Pro12Ala polymorphism did not significantly associate with PCOS, though the protective trend of G allele existed.

Calorie control increased vaspin levels of serum and periepididymal adipose tissue in diet-induced obese rats in association with serum free fatty acid and tumor necrosis factor alpha.

BACKGROUND: Vaspin was recently identified as a novel adipokine that is predominantly secreted from adipose tissue and exerts insulin-sensitizing effects. This study was undertaken to elucidate the regulative effects of calorie control on the expression of vaspin and its potential mechanism. METHODS: Diet-induced obese Sprague Dawley (SD) rats were adopted as experimental models and accepted interventions of various ingestions and pioglitazone. Various differentiated stages of cultured 3T3-L1 cells were dealt with pioglitazone or TNFalpha in vitro for 48 hours to further verify findings in animal experiments. RESULTS: The rats were successfully induced into an obese experimental model with hyperinsulinemia, hyperlipidemia, and increased serum free fatty acid and TNFalpha by 12-week high-fat diet. It was found that depending on whether the rats were fed by a high-fat diet or a basal diet, there was extremely higher vaspin in the periepididymal fat pad than in subcutaneous adipose tissues by 16 weeks. Vaspin in sera and the periepididymal fat pad was much lower in rats with a high-fat diet than those with a basal diet (all P < 0.05), but vaspin in subcutaneous fat tissues was prone to increase in rats with a high-fat diet. A 4-week calorie restriction or pioglitazone on the obese rats resulted in a partial recovery of vaspin levels in sera and periepididymal adipose tissues, especially the latter revealed a more obvious superiority and increased vaspin levels of subcutaneous adipose. Surprisingly, the treatment of 4-week high-fat diet on non-obese rats did not significantly depress vaspin of sera and periepididymal adipose tissues. However, it is unknown if re-feeding generated the effect on vaspin levels of obese and non-obese rats on sera or adipose tissues. The correlation analysis showed that vaspin levels of serum and periepididymal fat tissues were negatively correlated with serum FFA, TNFalpha and insulin; meanwhile, there was a positive correlation between serum vaspin and vaspin of periepididymal fat tissues. Pioglitazone enhanced vaspin levels in cultured 3T3-L1 cells and supernatant in various differentiated stages, and this effect became more and more obvious along with the change of preadipocytes into mature fat cells. Administration of TNFalpha caused suppression on vaspin expression in differentiated stages of 3T3-L1 cells. CONCLUSIONS: The present data indicated that a long-term high-fat diet could induce obesity metabolic syndrome in SD rats and finally lead to lower vaspin of sera and periepididymal fat, while pioglitazone and chronic calorie-control ingestion could enhance the production of vaspin. It was undoubtedly demonstrated that vaspin expression was strongly associated with insulin sensitivity, serum FFA, and TNFalpha.

[A novel mutation of 428delG in DAX-1 gene causing X-linked adrenal congenital hypoplasia].

OBJECTIVE: To investigate the clinical features and to identify the DAX-1 gene mutation in a Chinese kindred with X-linked adrenal hypoplasia congenital(AHC). METHODS: Clinical data and peripheral blood samples were obtained from the affected individuals and their relatives. The genomic DNA was isolated from whole blood. Four pairs of primers were used to amplify the two exons of the DAX-1 gene, and PCR products were purified and sequenced directly. Sequencing results were compared to the human DAX-1 sequence in the public database. RESULTS: A novel hemizygous frameshift mutation (428delG) in exon 1 of the DAX-1 gene was found in both patients (the index case and his cousin). Some clinical features such as the age of onset were different although these 2 patients carried the same mutation. Three females in the family, including the mothers of the 2 patients and their grandmother were carriers of this mutation. No such mutation was detected in other healthy persons in the family. CONCLUSION: The result suggested that X-linked AHC in the kindred was caused by a novel mutation of 428delG in the DAX-1 gene, and the same mutation can give rise to variable phenotypes.

["The severe degree of negligence" and its application in the settle of medical malpractice].

OBJECTIVE: To found the quantifiable index of "The severe degree of negligence" in describing the general severity degree of medical malpractice or medical dispute. METHODS: "The severe degree of negligence" can be calculated by the way of multiplying the coefficient of medical malpractice's grade by the coefficient of responsibility degree. RESULTS: There are 15 grades of "The severe degree of negligence" through calculation, from the severest degree of 1 to the lightest degree of 20. CONCLUSION: "The severe degree of negligence" can give an order of severe degree to different grade and different responsibility of medical malpractice. According to this order, the operation of medical malpractice and medical dispute settle will be easier and more rationality.

[Association of SNP276 in adiponectin gene with type 2 diabetes mellitus and insulin sensitivity].

OBJECTIVE: To investigate the distribution of SNP276 in adiponectin gene in Chinese Hans and its impact on type 2 diabetes mellitus and insulin sensitivity. METHODS: The study population consisted of 417 Chinese Hans residents in Anhui province, including 141 subjects with normal glucose tolerance (NGT) and 276 with type 2 diabetes (T2DM). The islet beta-cell insulin secretion and tissue insulin sensitivity were assessed by formulae of homeostasis model assessment (HOMA-IR & HOMA beta). Firstly, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to determine whether variation exists in APM1. Then, exact variation was detected by automated DNA direct sequencing. RESULTS: The genotypes of APM1 SNP276 were 0.489 GG, 0.418 GT and 0.092 TT and the major allele was G (frequency=0.699) in subjects with NGT. The distributions of genotypes and alleles of SNP276 both displayed significant difference between NGT and T2DM groups (P=0.031 and 0.013). The SNP276 non-TT (TG+GG) genotype was associated with increased risk of T2DM (OR=2.447, 95%CI: 1.067-5.612, P=0.035). In T2DM group, the subjects with SNP276 GG or GT genotype had higher body mass index, body fat content, fasting plasma glucose and HOMA-IR than did those with TT genotype (P < 0.05 or P < 0.01). Besides, GG genotype had higher systolic blood pressure (P=0.021). In NGT group, SNP276 non-TT carrier had increased body mass index, body fat content, waist hip ratio, fasting plasma insulin, oral glucose tolerance test 2 h plasma insulin and HOMA-IR when compared with TT genotype (P < 0.05 or 0.01). CONCLUSION: SNP276 in APM1 was associated with T2DM and insulin sensitivity.

[Study on the association of PPP1R3 gene polymorphism with type 2 diabetes in Han population of Anhui province].

OBJECTIVE: To study the association of muscle-specific glycogen-targeting regulatory subunit of the glucogen-bound protein phosphatase 1 (PPP1R3) gene codon 905 Asp/Tyr polymorphism with type 2 diabetes in Chinese Han population in Hefei region of Anhui province. METHODS: PPP1R3 gene Asp905Tyr polymorphism was detected by polymerase chain reaction and appropriate restriction enzyme (PCR-RFLP) in 262 type 2 diabetic cases and 104 normal controls. Case and control groups were divided into subgroups by body mass index (BMI) 25 kg/m2. RESULTS: When PPP1R3 gene Asp905Tyr polymorphism was not associated with type 2 diabetes mellitus. When subjects with BMI < 25 kg/m2 and Tyr/Tyr genotypes were used as reference. Subjects with Asp905 and BMI > or = 25 kg/m2 had a 3.69-fold increase of risk suffering from type 2 diabetes (OR = 3.69, 95% CI: 1.38-8.89, P=0.006). CONCLUSIONS: PPP1R3 gene Asp905Tyr polymorphism did not seem to play a critical role in the development of type 2 diabetes mellitus in Han population of Chinese in Anhui province but interaction between the Asp905 and BMI cause the increase of risk of type 2 diabetes.

[Study on association of PPP1R3 gene 5 bp deletion/insertion within 3'-untranslated region polymorphism with type 2 diabetes].

OBJECTIVE: To determine whether the muscle-specific glycogen-targeting regulatory subunit of the glucogen bound protein phosphatase 1 (PPP1R3) gene 5 bp deletion/insertion(D/I) within 3'-untranslated region ( 3'-UTR) polymorphism is associated with type 2 diabetes in Chinese Han population in Hefei region of Anhui province. METHODS: The PPP1R3 gene 3'-UTR 5 bp D/I polymorphism was detected by polymerase chain reaction in 268 patients with type 2 diabetes and 106 normal controls. RESULTS: (1) The distributions of the frequency of three genotypes and two alleles of the PPP1R3 gene 5 bp D/I polymorphism showed no significant difference between the type 2 diabetic cases and the normal controls. (2) In both the cases and controls, there was no significant difference in age at onset, duration of disease, blood glucose, blood lipid profile, blood pressure, insulin sensitive index, body mass index, and waist hip ratio between the three genotypic groups(P 0.05). (3) The PPP1R3 gene 3'-UTR polymorphism in Chinese Han population in Hefei region of Anhui province was found to be similar to that in both Japanese population and Canadian population, and to be different from that in Piman Indians and the Caucasians in Sweden. CONCLUSION: The PPP1R3 gene 5 bp D/I within 3'-UTR polymorphism taking on genetic variation among the different races of mankind may not play a critical role in the development of type 2 diabetes mellitus in Chinese Hans of Hefei region in Anhui province.