Risk Analysis Of Diabetes Based On Family History And The Screening Of The Mt3243A>G Mutation In Community-based Diabetic Patients

Aims: We explored the relationship of different family history risk levels and the risk of diabetes in a multi high-risk cohort.The influence of family history of diabetes on insulin secretion and insulin sensitivity was also assessed.And we explored a non-invasive method to detect the mt3243 A > G mutation rapidly in elderly Chinese type 2 diabetic patients.Materials and Methods: A total of 9754 adults participating in the Shanghai High-Risk Diabetic Screen Project between 2002 and 2012 were enrolled in the study.Risk of diabetes based on family history of diabetes were classified as average,moderate and high familial risk level.We evaluated how different risk levels of famly history were associated with the prevalence of diabetes,insulin secretion and insulin sensitivity in this multi high-risk cohort.In addition,a total of 1041 patients with type 2 diabetes from diabetic community-based peer-education project were included in this study.High resolution melting curve(HRM)was performed to detect the mt3243 A > G mutation in DNA extracted from urine sediments,followed by the pyrosequencing that was used to quantify the level of the heteroplasmy.And blood,saliva and urine sediment samples were collected from patients with the mt3243 A > G mutation and the family members for further analysis.Detailed clinical examination including audiometric,ophthalmologic,neurological and cardiac examination were conducted to assess the impact of the mt3243 A > G mutation on multi organs.Results: We found the distribution of participants were as follows: 69.6% were in the averagefamilial risk level,24.8% were in the moderate familial risk level and 5.6% were in the highfamilial risk level,respectively.The standardized prevalence of diabetes was the highest inthe high familial risk level(43.1%)and the lowest in the average familial risk level(23.5%)(P < 0.001).Compared with that in the average familial risk level,odds ratios(ORs)in the moderate familial risk level and high familial risk level were significantly increased by 27% an 69%,respectively(all P < 0.05).In the normal glucose tolerance group,the result showed that early-phase insulin secretion decreased with higher familial risk levels,while no significant differences in insulin sensitivity among the three familial risk levels.We identified two patients(2/1041)with the mt3243 A > G mutation in the diabetic community-based peer-education project.The heteroplasmy of the mutation was measured in blood,saliva and urine sediments from the two patients.In patient F1955II-1,the heteroplasmy was 0.8%,2.8% and 14.7% in peripheral blood leukocytes,saliva and urine sediment,respectively.In patient F1956II-1,the heteroplasmy was 5.3%,8.4% and 37.7% in peripheral blood leukocytes,saliva and urine sediment,respectively.F1955II-1 had newly diagnosed bilateral sensorineural hearing loss at all frequencies according to the results of the audiogram.Results of ophthalmologic examination indicated electrophysiological dysfunction of cone cells.The main findings of the MRI were hyperintensity on T2-weighted images of the bilateral frontal lobe,bilateral parietal lobe,basal ganglia and corona radiate.Conclusion: Among multi high-risk Chinese populations,the risk of diabetes was associated with higher family history risk levels independently.And even among participants with the normal glucose tolerance,in comparison to those in the average familial history risk level,individuals in the moderate and the high familial history risk levels showed decreased early-phase insulin secretion.In addition,the occurrence of the mt3243 A > G mutation among middle-aged and elderly type 2 diabetic patients from China was 0.2%.Furthermore,to detect this mutation in urine sediment by high resolution melting curve(HRM)and pyrosequencing will contribute to non-invasive molecular diagnosis.