Diets, Genetic Polymorphisms And Glycemic Control Status In Chinese Adults With Type2Diabetes

Background and Objective:Type2diabetes （T2DM） is a complex and multifactorial chronic disease characterized with impaired glucose metabolism that may lead to a variety of acute and chronic complications and premature death. Diet, physical activity, medicine use and genetic factors have been suggested the main factors affecting the progress of T2DM. To evaluate the impact of diet and susceptible genetic polymorphisms on glycemic control status in Chinese patients with T2DM, we conducted two repeated cross-sectional surveys among934patients with T2DM from Pudong New Area of Shanghai. China. We also evaluated the associations of genotypes with metabolic phenotype among918healthy volunteers from same communities aimed at better understanding the potential functions of the selected genetic polymorphisms.Methods:1. The1st cross-sectional survey:A total of934Chinese adults diagnosed with T2DM were randomly selected from the Diabetes Administration Rosters in communities of Shanggang. Zhoujiadu, Huamu, Puxin, Weifang, Jinyang, Meiyuan and Jichang of Pudong New Area of Shanghai during the period of Oct. to Dec.,2006. At the same time, a total of918adult volunteers free of diabetes were recruited from the communities mentioned above. A structured in-person interview was conducted for each subject by trained interviewers to collect information on demographic characteristics, duration of diabetes, age at onset of diabetes, life style factors such as use of tobacco and alcohol, and dietary habit assessed with a validated food frequency questionnaire （FFQ）. At the interview, each participant was measured for his/her body height, weight, waist circumference, hip circumference, systolic blood pressure （SBP）. and diastolic blood pressure （DBP） according to a uniform and standardized protocol. Blood samples were collected for the measurement of total cholesterol （TC）, triglyceride （TG）, high density lipoprotein cholesterol （HDLC） and low density lipoprotein cholesterol （LDLC）.2. The2nd cross-sectional survey:During the period of Aug. and Sep.,2011, all934diabetic patients in the1st survey were interviewed for the second time with a similar questionnaire and protocol.3. Single nucleotide polymorphisms （SNPs） of TCF7L2-rs290487, CDKAL1-rs9465S71and rs1359790at13q31.1were genotyped by Taqman allelic discrimination assays （assay ID:C₁349543₁0for rs290487; C₂9598297₁0for rs9465871and C₇442164₁0for rs1359790; Applied Biosystems） on an ABI7900HT system.4. Statistical analyses were conducted utilizing SAS statistical software9.2（SAS Institute Inc., Cary, NC）. Differences on demographic factors were evaluated using x2test for categorical variables or non-parameter Wilcoxon test for continuous variables. A generalized linear regression model was employed to compare average levels of biochemical indicators and dietary intake. Tests for multiplicative interactions were performed by including two main effects and a cross-product term in the regression model. An unconditional logistic regression model was applied to estimate the adjusted odds ratios （ORs） and95%confident intervals （CIs） of dietary intake with glycemic control status among diabetic patients. An analysis of covariance model （ANCOVA） was used to evaluate the associations of SNPs with HbAlc levels and with the difference of HbAlc levels between two surveys. All statistical tests were based on two-sided probability and P-values<0.05were considered as statistically significant.Results:1. Among918healthy Chinese adults free of diabetes, no significant association was observed for genotypes at TCF7L2-rs290487or at13q31.1-rs1359790with metabolic phenotypes such as the levels of triglycerides （TG）. high-density lipoprotein （HDLC）, waist circumference （WC）, fasting plasma glucose （FPG） or glycolated hemoglobin ALc （HbA1c）. However, a significant increase was observed for average levels of FPG and HbA1c with increasing number of C allele at CDKAL1-rs9465871. We further found that the effect of C allele of CDKAL1-rs9465871on HbA1c level reached statistically significant only among women.2. Among diabetic patients, HbA1c level was negatively correlated with dietary fiber intake. Regardless of duration of the disease, HbA1c level was consistently higher in patients consuming lower level of fiber. Among934subjects participating in the1st suvey, the adjusted ORs for poor glycemic control status （HbA1c≥7.0%） was0.76（95%CI:0.54-1.07） for the patients having medium intake of dietary fiber and0.52（95%CI:0.35-0.76） for those with the highest tertile intake （P for trend<0.001） compared with the patients having the lowest tertile intake. The protective effect of dietary fiber intake on the glycemic control status was observed to last for five years among508patients who participated in both surveys.3. Among508patients participating in both surveys, a significant lower HbA1c level was observed in the second survey than in the first one. The average decrease of HbA1c differed significantly among genotypes of13q31.1-rs1359790. but not among those for other two SNPs. The median decrease of HbA1c level was0.25%for GG genotype,0.60%for AG genotype and0.38%for AA genotype of rs1359790. After adjusting for potential confounding factors, a borderline significant decreasing trend was observed for the changes of HbA1c level with increasing G allele at rs1359790（P=0.102）. We further found that dietary fiber intake modified the effect of rs1359790on the changes of HbA1c level（P for interaction=0.034）. Among subjects consuming lower level of dietary fiber. GG genotype of rs1359790was linked to a more pronounced decrease in HbA1c level than AA+AG genotypes. Conclusions:The effect of CDKAL1-rs9465871on HbAlc level among Chinese adults free of diabetes indicates that the SNP may involve in the regulation of insulin secretion through which it confer risk to T2DM in the population. Dietary fiber intake plays an important role in glycemic control status in Chinses patients with T2DM. while the SNP of13q31.1-rs1359790is significantly associated with a long term change of HbAlc level, especially among those consuming lower dietary fiber. Our results indicate that increasing fiber intake may be an effective approach to improve glycemic control status among Chinese diabetic patients, particularly among those with GG genotype at13q31.1-rs1359790.