Association Study Of Islet Amyloid Polypeptide(IAPP) And IAPP Gene Ser20gly Mutation With Bone Mineral Density Of Type 2 Diabetes Mellitus In YunNan Han Population

Amylin (islet amyloid polypeptide, IAPP) expression was found in the islets amyloid of patients with type 2 diabetes mellitus(T2DM), as well as in the islet beta cells of normal pancreas It is a polypeptide hormone produced in islet beta cells and may lead to the insulin resistance and beta-cell dysfunction. In some studies, positive association was found between IAPP gene Ser20Gly mutation and inpaired glucose tolerance in Japanese population, but the frequencies of Ser20Gly mutation and its association with T2DM in YunNan Han population is unknown. On the other hand, IAPP plays a critical role in bone metabolism. It can stimulate the proliferation of osteoblastic and may acts as an inhibitor of bone reabsorption, In this study, we aim to investigate the relationships of serum IAPP levels and IAPP gene S20G mutation with bone mineral density of patients with T2DM.Objective1. To study the association between the serous IAPP levels and the bone mineral density of T2DM's patients.2. To the evaluate the frequencies of the IAPP gene S20G mutation in Yunnan Han ethnic population.3. To investigate the association between IAPP gene S20G mutation and bone mineral density of T2DM's patients.Method In the first part of the study,266 unrelated YunNan Han individuals (T2DM 149, non-diabetes 119) with right dominant hand were included in this study. Height, weight, waist circumference, hip circumference, fasting IAPP, blood glucose, insulin, C-peptide, lipid, blood calcium, phosphate and the function of the liver and kidney were measured. Bone mineral density was measured with dual X-ray absorptiometry of the left fore arm. In the second part of this study,167 T2DM and 121 non-diabetes (ND) were enroled, all of them are unrelated Han race and resident in YunNan province. IAPP Ser20Gly mutation was examined by PCR-RFLP method.10% PCR products were randomly selected to perform direct DNA sequencing.Result1. The incidence rate of osteoporosis is 27.5% in T2DM and 3.4% in ND, that higher in T2DM than ND (P＜0.001).2. In all subjects, T-score of the left forearm is association with age, sex, BMI, and IAPP. T-score is negatively associated with age, and positively associated with BMI, IAPP. In T2DM, after adjusting for sex, BMI, diabetes duration, hypertension, and cigrarette smoking, T-score was negatively associated with age(r=-0.062, P＜0.001) and positively with IAPP(r=0.027, P＜0.01). After adjusting for sex and GFR, T-score in ND was negatively significantly associated with age r=-0.035, P＜0.001),and positively associated with IAPP (r=0.018, P＜0.01) and BMI(r=0.099, P＜0.001).3. In all subjects, logistic analysis indicates that every increment of 1μl/ml of IAPP may lead to 10.2% risk reduction of osteoporosis.4. Only one Ser20Gly heterozygotic mutation was found in T2DM subjects, no Ser20Gly mutation was observed in ND group. The frequency of IAPP Ser20Gly mutation is 0.6% in T2DM group and no significant differences was found between T2DM and ND group. (Fisher two-tailed exact, P＞0.05).Conclusions After correction for sex, BMI,GFR, diabetic duration, hypertension duration, and cigarette smoking, fasting serum IAPP level is positively associated with bone mineral density in T2DM patients, suggesting JAPP might be a protective factor for bone mass metabolism in T2DM. Low frequency of IAPP gene Ser20Gly mutation was found in YunNan Han T2DM, but no positive association was observedbetween this mutation and T2DM, as well as with bone mineral density.