目的 观察新疆石河子地区绝经后女性2型糖尿病(T2DM)患者糖、脂、骨代谢特征及骨密度(BMD)情况,探讨该人群中低密度脂蛋白受体相关蛋白5(LRP5)基因rs3736228、rs3781586位点的基因多态性及突变与糖、脂、骨代谢指标的关系。方法 将新疆石河子地区2016年10月—2017年10月社区、医院门诊及住院绝经后女性按照纳入标准和排除标准选取136例为研究对象,根据患者病史、糖耐量实验及骨密度仪测定骨密度分4组,糖耐量正常与骨量正常组(A组),糖耐量正常与骨量异常组(B组),T2DM与骨量正常组(C组),T2DM与骨量异常组(D组)。测定并记录患者年龄、绝经年限等基线资料,计算体质指数(BMI)等,并检测糖代谢指标(空腹血糖等)、骨代谢指标(血Ca等)、脂代谢指标(甘油三酯等)。采用MALDI-TOF-MS法测定LRP5基因该两个位点基因多态性并进行统计分析。结果 ①糖代谢指标:与A组比较,C组、D组FPG、HbA1c均高于A组(P<0.01)。脂代谢指标:与A组比较,B组、D组TG低于A组(P<0.05)。骨代谢指标:与A组比较,B组、D组BMD(L1-4)、BMD(股骨颈)低于A组(P<0.01)。②LRP5基因该两个位点SNP基因分型分布符合Hardy-Weinberg遗传平衡定律(P>0.05);同时,该两个位点不同基因型的分布频率和等位基因频率在组间的比较经Pearson Chi-Square检验后发现暂无显著差异(P>0.05)。③LRP5基因rs3736228位点:A组,与CC型(野生型)相比,CT/TT型(突变型)甘油三酯(TG)降低(P<0.05),BMD(L1-4)降低(P<0.05);C组,与CC型(野生型)相比,CT/TT型(突变型)高密度脂蛋白(HDL-C)升高(P<0.01),磷(P)升高(P<0.05);LRP5基因rs3781586位点:B组,与GG型(野生型)相比,GT/TT(突变型)高密度脂蛋白(HDL-C)升高(P<0.05)。结论 在新疆石河子地区绝经后女性2型糖尿病人群中,LRP5基因rs3736228、rs3781586位点的基因多态性可能与糖代谢无关,但LRP5基因rs3736228位点的突变可能与脂代谢(TG、HDL-C)、骨代谢(P、BMD)有关,rs3781586位点的突变可能与脂代谢(HDL)有关。

Objective To observe the characteristics of glucose, lipid and bone metabolism and bone mineral density (BMD)in postmenopausal women with type 2 diabetes mellitus (T2DM)in Shihezi district of Xinjiang province, and to investigate the relationship in the polymorphism and mutation of rs3736228 and rs3781586 of LRP5 gene and glucose,lipid and bone metabolism indexes in this population. Method A total of 136 postmenopausal Han women, who were related in the outpatient department, community, and hospital after hospitalization in Shihezi district of Xinjiang province from October 2016 to October 2017, were selected as the study subjects by the inclusion criteria and exclusion criteria.According to the patient's medicalhistory, glucosetolerance test results and bone mineral density (BMD), they were divided into 4 groups: normal glucose tolerance and normal bone mass (group A), normal glucose tolerance and abnormal bone mass (group B), type 2 diabetes and normal bone mass (group C), and type 2 diabetes mellitus and abnormal bone mass (group D). Baseline data such as patient's age, menopause years were measured and recorded, and body mass index (BMI)was calculated. Simultaneously, glucose metabolism indicators including fasting blood glucose (FBG, etc), bone metabolism indicators (blood Ca, etc), lipid metabolism indicators(triglycerides, etc)were detected. The polymorphisms of rs3736228 and rs3781586 of LRP5 gene were determined by Maldi-Tof-Ms and those data were analyzed statistically. Results ①Glucose metabolism index: compared with group A: FPG and HbAlc in group C, group D were all higher than group A (P<0.01). Lipid metabolism index: compared with group A, TG in group B and group D was lower than that in group A (P<0.05). Bone metabolism index: compared with group A, BMD (L1- 4)and BMD (femoral neck)in group B and group D were lower than those in group A (P<0.01). ②The distribution of SNP genotypes at rs3736228, rs3781586 of LRP5 conformsed to the Hardy-Weinberg genetic equilibrium law (P>0.05). The distribution frequency and allele frequency of LRP5 genotypes rs3736228, rs3781586 were compared among the groups. Pearson chi-square test showed no significant difference (P>0.05). ③Rs 3736228 locus of LRP5 gene:in group A, compared with CC (wild type), CT/TT (mutated type)triglyceride (TG)decreased (P<0.05), BMD (L1- 4)decreased (P<0.05). In group C, compared with CC (wild type), CT/TT (mutated type)high-density lipoprotein (HDL-C)increased (P<0.05), phosphorus increased (P<0.05). Rs 3781586 locus of LRP5 gene: in group B, compared with GG (wild type), GT/TT (mutated type)high-density lipoprotein (HDL-C)increased (P<0.05).Conclusion In the Xinjiang Shihezi district among postmenopausal women with type 2 diabetes, rs3736228, rs3781586 loci of LRP5 gene polymorphism may be irrelevant to glucose metabolism, but the mutation of rs3736228 of LRP5 gene locus may be related to lipid metabolism and bone metabolism (TG, HDL-C, BMD, P), and the mutation of rs3781586 may be related to lipid metabolism (HDL-C).

目的 探讨利拉鲁肽与二甲双胍对新诊断2型糖尿病患者骨代谢的影响。方法 选取2016年1月—2017年6月在我院就诊并确诊为新诊断2型糖尿病患者50例,按照随机数字表法将研究对象随机分为利拉鲁肽组及二甲双胍组,每组各25人。两组患者均单药治疗24周后比较两组患者骨密度、骨代谢指标变化情况。结果 两组患者骨密度、血清ALP以及BGP、PINP水平治疗前后相比,无改变(P>0.05);而利拉鲁肽组患者的β-CTx水平较治疗前降低(P<0.05);两组患者治疗后FPG、2hFPG、HOMA-IR、HbA1c均较治疗前下降(P<0.05),而空腹胰岛素较治疗前上升(P<0.05);利拉鲁肽组患者治疗24周后BMI值低于治疗前(P<0.05)。结论 利拉鲁肽与二甲双胍对新诊断2型糖尿病患者骨密度的影响均不明显,两种药物可有效降低血糖,改善胰岛素抵抗,利拉鲁肽在使用过程中可明显降低患者血清β-CTx水平,但其是否存在骨质保护作用仍需进一步研究。

Objective To explore the effect of liraglutide and metformin on bone metabolism in newly diagnosed type 2 diabetic patients. Methods From January 2016 to June 2017, 50 patients with type 2 diabetes mellitus admitted to our hospital were selected. According to the random number table method, the subjects were randomly divided into liraglutide group and metformin group, 25 in each group. Changes in bone mineral density and bone metabolism were compared between the two groups after 24 weeks of monotherapy. Results That there was no significant change in bone mineral density, serum ALP, TPINP,and BGP levels before and after treatment (P>0.05). The β-CTx levels in patients in the liraglutide group were lower than that before treatment (P<0.05); FPG, 2hFPG, HOMA-IR, and HbA1c levels in the two groups were lower than that before treatment (P<0.05). Fasting insulin was higher than that before treatment (P<0.05); BMI was lower in the liraglutide group after 24 weeks of treatment than that before treatment (P<0.05). Conclusion The effects of liraglutide and metformin on the bone mineral density of patients with newly diagnosed type 2 diabetes are not obvious. Liraglutide may reduce serum β-CTx levels during use. We need to have further study whether it has a bone protection.

目的 通过比较治疗组服药前、后骨密度及骨代谢指标的变化情况,并将治疗组、对照组分别作对比,观察壮骨颗粒治疗绝经后女性骨量减少及骨质疏松、改善其骨代谢的临床疗效。方法 将研究对象随机分为两组,治疗组服用壮骨颗粒＋迪巧,对照组只服用迪巧。结果 壮骨颗粒组治疗后血清中的PINP、β-Crosslaps及N-MID下降(P＜0.05);与治疗前相比,腰椎(L2-L4)BMD提高(P＜0.05);壮骨颗粒能改善绝经后女性骨代谢及提高骨密度的效果优于迪巧组。结论 壮骨颗粒是治疗绝经后女性骨量减少及骨质疏松、提高骨量、改善骨代谢情况的安全有效药物。