不同剂量维生素D加钙干预对中老年糖耐量减低患者血糖和胰岛素敏感性的影响

Effect of different doses vitamin D and calcium supplementation on blood glucose and insulin sensitivity in middle-aged and elderly patients with impaired glucose tolerance

目的探索不同剂量维生素D（VitD）＋钙对中老年糖耐量减低（IGT）患者血糖及胰岛素敏感性的影响。 方法选择2013年1月至2015年5月50~65岁在我院老年科进行体检的IGT患者150例，其中男性80例，女性70例，平均年龄（57±4）岁，按随机数字表法分为3组：常规剂量组（A组，n= 49, VitD 125 U/d＋钙600 mg/d），双倍剂量组（B组，n=51，VitD 250 U/d＋钙1 200 mg/d），未服药的对照组（C组，n=50）。基线及VitD＋钙干预6、12个月后均进行口服葡萄糖耐量试验（OGTT），检测血液生化指标，并计算稳态模型胰岛素抵抗指数（HOMA-IR）及稳态模型胰岛β细胞功能指数（HOMA-β）。多组间数据比较采用重复测量的方差分析，若P〈0.05，两两比较采用LSD-t检验，相关性分析则采用Pearson相关分析和多元逐步回归分析。 结果（1）与C组相比，治疗6、12个月后的A、B组空腹血糖（FPG）、服糖后2 h血糖（2 h PG）及2 h胰岛素（2hINS）、糖化血红蛋白（HbA1c）、HOMA-IR均有显著下降，血清25（OH）D、HOMA-β等均有显著升高（均P〈0.05）。（2）治疗6、12个月后A组[（5.7±0.2）%、（5.6± 0.6）%]和B组的HbA1c[（5.7±0.6）%、（5.5±0.4）%]均低于治疗前[（5.9±0.5）%、（5.9±0.6）%]，且HOMA-IR（分别为3.6±1.1、3.4±1.5比2.8±1.5、2.0±1.2）低于治疗前（3.8±0.9、3.7±0.7）；FPG、2 h PG也低于治疗前，差异有统计学意义（均P〈0.05）。（3）治疗12个月后，B组的空腹胰岛素（FINS）、2hINS、HbA1c及HOMA-IR均低于A组，而25（OH）D水平高于A组[（40±5）比（32±6）μg/L]，差异均有统计学意义（均P〈 0.05）。（4）Pearson相关分析显示，治疗12个月后25（OH）D水平与HOMA-β、血钙呈正相关（r=0.210、0.444，均P〈0.05）；与HbA1c、FPG、HOMA-IR呈负相关（r=-0.241、-0.215、-0.225，均P〈0.05）。多元逐步回归分析显示，IGT患者的25（OH）D的水平与HbA1c、治疗方式（常规剂量和双倍剂量）以及总胆固醇显著相关（t=2.138、7.16、7.33、2.319，均P〈0.05）。 结论中老年IGT患者补充VitD＋钙后血糖水平和胰岛素敏感性改善，疗效呈剂量及时间依赖性。

ObjectiveTo explore the effect of different doses of vitamin D （VitD） and calcium supplementation on blood glucose and insulin sensitivity in middle-aged and elderly patients with impaired glucose tolerance （IGT）. MethodsA total of 150 individuals with IGT [aged （57±4） years] were chosen during physical examination from January 2013 to May 2015, of which 80 cases were male and 70 were female. They were randomly divided into three groups： regular dose group （group A, n=49, VitD 125 U/d ＋ calcium 600 mg/d）, double dose group （group B, n=51, VitD 250 U/d ＋ calcium 1 200 mg/d）, and control group （group C, n=50, no medication）. Oral glucose tolerance test （OGTT） was performed before and after VitD and calcium supplementation. Blood biochemical parameters were measured. Homeostasis model assessment （HOMA） insulin resistance index （HOMA-IR） and HOMA islet β-cell function index （HOMA-β） were calculated. Comparison of means was done by one-way analysis of variance （ANOVA）. LSD-t test was used when P〈0.05 as the limit for statistical significance.appropriate. Correlation analysis was performed using Pearson correlation analysis and multiple stepwise regression analysis. Results（1） Compared with group C, fasting plasma glucose （FPG）, 2-hour plasma glucose （2hPG） and insulin （2hINS）, glycated hemoglobin A1c （HbA1c）, HOMA-IR in group A and B declined significantly （P〈0.05） after 6 and 12 months of VitD and calcium treatment, while the level of serum 25（OH）D and HOMA-β were dramatically increased （all P〈0.05）. （2） After 6 and 12 months treatment, HbA1c, HOMA-IR significantly declined from baseline [HbA1c： （5.9±0.5）%,（5.9±0.6）%; HOMA-IR：（3.8±0.9, 3.7±0.7）] in group A [HbA1c：（5.7±0.2）%, （5.6± 0.6）%; HOMA-IR： 3.6±1.1, 3.4±1.5] and group B [HbA1c：（5.7±0.6）%,（5.5±0.4）%; HOMA-IR： 2.8±1.5 vs 2.0±1.2] （all P〈0.05）. And the levels of FPG and 2hPG were also reduced. The differences were significantly （all P〈0.05）. （3） In addition, FINS, 2hINS, HbA1c and HOMA-IR in 12 months after treatment were declined in group B compared with group A, while the level of serum 25（OH）D in group B was increased [（40±5） vs （32±6） μg/L] （all P〈0.05）.（4） Pearson correlation coefficient analysis showed that serum 25（OH）D in 12 months post-treatment was positively correlated with HOMA-β （r=0.210）, serum calcium （r=0.444） （both P〈 0.05）; while was negatively correlated with HbA1c（r=- 0.241）, FPG （r=- 0.215） and HOMA-IR （r=- 0.225） （P〈0.05）. Multiple regression analysis indicated that serum 25（OH）D in patients with IGT was markedly positively correlated with HbA1c（r=2.138） VitD doses （r=7.160 for regular-dose, 7.330 for double dose） and total cholesterol （r=2.319） （P〈0.05）. ConclusionVitamin D and calcium supplementation can improve blood glucose and insulin sensitivity in middle-aged and elderly patients with IGT, in a dose and time dependent manner.