| Objective l.To study the clinical characters of the patients with diabetes before 40 years, the effects of the diabetic family history and obesity on the phenotypes of those patients, and the effects of routine therapy on the nature history of DM. 2. To investigate the prevalence of IAPP S20G, mitochondrial DNA A3243G, PTP-IB P387L and Pax4 R121W mutation and the mutation of partial exons of HNF-la gene in Chinese patients with early onset type 2 diabetes mellitus. 3. To study the role of I27L amino acid polymorphism of hepatocyte nuclear factor-la in the pathogenesis of early onset diabetes mellitus. To study the relationship between the genotype with the phenotype.Methods Enrolled 234 diabetic patients who onset diabetes before the age of 40 years. The parameters of the glucose and lipid metabolism, anti-GAD antibody, the rate of diabetic family history(FH) and insulin resistance index(HOMAIR) were measured using routine methods. Those patients also divided into two subsets according to their diabetic FH and BMI. To follow-up 110 patients who onset diabetes in one year for 3 years. During the 3 years they received routine therapy. Using PCR-RFLP, SSCP plus direct sequencing technique to detect the mutation of mentioned genes in those patients. To collect the clinic data in the affected patients and their family members. There were 92 normal persons as control.Results 1 .The FBG, PBG2h and BMI, TG of early onset diabetic patients were higher than the normal health persons'. HbAlc was 10.4?.4%. HOMAIR was 3.63~8.60.The rate of GAD autoantibody positive was 3.64%.There were more than 80% diabetic patients used diet and oral agent therapy. 18% of those patients used insulin treatment.Though BMI, WHR, BP and HOMAIR were slightly higher in FH+ diabetic patients than in FH- patients, there was no significantly difference between two groups. HDL level was higher in FH- group than in FH+ group(1.23?.30 vs 1.35?.31mmol/L, P=0.004). There were significantly difference between obesity and non-obesity diabetic groups in BP ( 125.20?9.05 vs 119.80?6.93mmHg,P=0.043 ) ,TG(1.74[1.21,3.00] vs1.12 [0.82, 1.69], P=0.001), FIRI(15.00[13,21] vs 11.00[8,14], P=0.001), FCP (2.30 [1.65,2.8] vs 1.30[0.9,1.9], P=0.001) and HOMAIR (6.11[4.34,8.81] vs 4.84 [3.32,6.89], P=0.02). HDL level was lower in obesity patients(1.20?.27 vs 1.32?.30mmol/L,JP= 0.001).The FBG was lower in obesity group(9.23?.14 vs 10.59?.99mmol/L,P= 0.02).After routine therapy the glucose control was improved in 110 patients during 3 years follow-up. HbAlc level was 10.57?.47 at baseline, 8.66?.73 at the first year and 8.3H1.89 at the 3th year, P<0.01. The TC level was significantly higher at the 3th year compared with the baseline (5.13?.74mmol/L vs 4.87?.21mol/L,P<0.01).2.One case with mitochondrial DNA A3243G mutation and 2 cases with IAPP S20G mutation were found in those 234 patients. One of the IAPP S20G mutation patients was homozygous and another one was heterozygous. No PTP-1B P387L and Pax4 R121W mutation were found. No mutation in exons 3,4,6,8,10 of HNF-la gene. Among 14 cases of the family study, the another 5 patients with mitochondrial DNA A3243G mutation were found. Three cases had diabetes mellitus. Two cases' OGTT were normal. The clinical characters of those patients were that they have deafness with or without diabetes mellitus. They were lean and using insulin therapy soon after the diabetes onset. Those patients onset diabetes between age 31-40 years, FCP 0.2-1.2ng/ml, HOMAIR 2.21-3.62, In the families of the affected patients with IAPP mutation another 2 affected patients were found. One was homozygous carrier and another one was heterozygous one. They all had diabetes mellitus. The onset age of diabetes was 31-38 years old, BMI 18.9-26.4kg/m2, FCP 1.87 -3.61ng/ml, HOMAIR 5.04-8.27. To follow-up one IAPP homozygous carrier for 4 years the results revealed the FCP and Glucogan stimulated C peptide level (SCP) had the trend to decline. In normal control group no those mutations were found.3.There were 36% II, 46% IL a...
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