Hagström E, Hellman P, Lundgren E, Lind L, Arnlöv J
Department of Surgical Sciences, Uppsala University, SE-751 85, Uppsala, Sweden.
Diabetologia. 2007 Feb;50(2):317-24. doi: 10.1007/s00125-006-0532-9. Epub 2006 Dec 20.
AIMS/HYPOTHESIS: Diabetes mellitus type 2 is associated with altered calcium metabolism. Moreover, in diseases with supranormal serum calcium levels, such as primary hyperparathyroidism, the prevalence of diabetes is increased. Relatively little is known about the relationship between serum calcium concentration and the underlying causes of diabetes-insulin resistance and defective insulin secretion-in the normocalcaemic general population.
We investigated associations between serum calcium concentration and insulin sensitivity and secretion in a population-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men, n = 961). Insulin sensitivity index (M/I; glucose disposal rate [M] divided by mean insulin concentration [I]) was assessed using euglycaemic-hyperinsulinaemic clamp, and insulin secretion was estimated from the early insulin response (EIR) during an OGTT.
In a multivariable linear regression model adjusting for BMI, physical activity, smoking, consumption of tea, alcohol, coffee and dietary calcium, serum phosphate and serum creatinine, 1 SD increase in serum calcium was associated with 0.17 mg kg(-1) min(-1) (mU/l)(-1) x 100 (0.024 mg kg(-1) min(-1) pmol/l x 100) decrease in M/I (p = 0.01). The results remained robust in individuals with normal fasting glucose, normal glucose tolerance and serum calcium within the normal range (n = 413, regression coefficient for 1 SD increase -0.45, p = 0.001). Serum calcium was not associated with EIR. Dietary intake of calcium was not independently associated with insulin sensitivity or EIR.
CONCLUSION/INTERPRETATION: Our data support the notion that endogenous calcium may be involved early in the development of diabetes and that this effect is mediated mainly through effects on insulin sensitivity rather than defective insulin secretion. Dietary intake of calcium does not seem to influence insulin sensitivity.
目的/假设：2型糖尿病与钙代谢改变有关。此外，在血清钙水平超常的疾病中，如原发性甲状旁腺功能亢进症，糖尿病的患病率会增加。在血钙正常的普通人群中，关于血清钙浓度与糖尿病潜在病因（胰岛素抵抗和胰岛素分泌缺陷）之间的关系，人们了解得相对较少。
我们在一个基于人群的老年男性队列（乌普萨拉成年男性纵向研究，n = 961）中，研究了血清钙浓度与胰岛素敏感性及分泌之间的关联。使用正常血糖-高胰岛素钳夹技术评估胰岛素敏感性指数（M/I；葡萄糖处置率[M]除以平均胰岛素浓度[I]），并通过口服葡萄糖耐量试验（OGTT）期间的早期胰岛素反应（EIR）来估计胰岛素分泌。
在一个多变量线性回归模型中，对体重指数、身体活动、吸烟、茶、酒精、咖啡和膳食钙的摄入量、血清磷酸盐和血清肌酐进行校正后，血清钙每增加1个标准差，M/I降低0.17 mg·kg⁻¹·min⁻¹·(mU/L)⁻¹×100（0.024 mg·kg⁻¹·min⁻¹·[pmol/L]⁻¹×100）（p = 0.01）。在空腹血糖正常、葡萄糖耐量正常且血清钙在正常范围内的个体中（n = 413，血清钙每增加1个标准差的回归系数为 -0.45，p = 0.001），结果依然稳健。血清钙与EIR无关。膳食钙摄入量与胰岛素敏感性或EIR无独立关联。
结论/解读：我们的数据支持内源性钙可能在糖尿病发病早期就起作用这一观点，且这种作用主要是通过对胰岛素敏感性的影响而非胰岛素分泌缺陷介导的。膳食钙摄入量似乎不影响胰岛素敏感性。
