Barbagallo M, Gupta R K, Resnick L M
Division of Endocrinology, Wayne State University, Detroit, Michigan 48201, USA.
Diabetes Care. 1996 Dec;19(12):1393-8. doi: 10.2337/diacare.19.12.1393.
To investigate the role of hyperglycemia in mediating the clinical association of NIDDM with hypertension and left ventricular dysfunction and hypertrophy.
Since hyperglycemia elevates cytosolic free calcium (Cai) both in myocardial and vascular smooth muscle cells, we utilized nuclear magnetic resonance (NMR) spectroscopy to measure erythrocyte Cai levels and compared them with serum ionized calcium (Caio), glucose, and insulin values before and following an oral glucose tolerance test (OGTT) and with previously obtained cardiac structural indexes in normotensive and hypertensive NIDDM (n = 32) and normal control subjects (n = 35).
Compared with control subjects, normotensive NIDDM subjects had higher Cai (31.5 +/- 2.3 vs. 24.3 +/- 1.9 nmol/l, P = 0.05), lower intracellular free magnesium (Mgi) (200 +/- 10 vs. 225 +/- 7 mumol/l, P = 0.05), and greater posterior wall thickness (0.98 +/- 0.04 vs. 0.86 +/- 0.03 cm, P = 0.05). Hypertensive NIDDM subjects exhibited a further increase in Cai (43.1 +/- 4.4 nmol/l, P = 0.05 vs. control subjects) and left ventricular mass (LVM) (201.5 +/- 12.2 vs. 155.8 +/- 7.7 g, P = 0.05 vs. control subjects). For all subjects, significant relationships were observed between Cai and fasting blood glucose (r = 0.510, P < 0.01), HbAic (r = 0.389, P < 0.05), and the glycemic response to OGTT (the area under the curve [AUC] for glucose; r = 0.519, P < 0.01) and to systolic (r = 0.504, P < 0.01) and diastolic (r = 0.624, P < 0.01) blood pressure. Left ventricular mass index (LVMI) was related to fasting glucose levels (r = 0.406, P < 0.01) and the AUC for glucose (r = 0.380, P < 0.01), but not to fasting insulin or insulin responses to an OGTT. The LVMI was best related to Cai (r = 0.516, P < 0.01), while being inversely related to Caio (r = -0.486, P < 0.01). Multivariate regression indicated the contribution of glucose to LVMI was independent of age, BMI, insulin, and blood pressure but demonstrated a significant interaction with Cai.
Altogether, these data suggest that glucose-related excess Cai is a fundamental lesion in diabetes that contributes to the elevated blood pressure and cardiac mass in this disease.
研究高血糖在介导非胰岛素依赖型糖尿病（NIDDM）与高血压及左心室功能障碍和肥厚的临床关联中的作用。
由于高血糖会升高心肌和血管平滑肌细胞中的胞质游离钙（Cai），我们利用核磁共振（NMR）光谱法测量红细胞Cai水平，并将其与口服葡萄糖耐量试验（OGTT）前后的血清离子钙（Caio）、葡萄糖和胰岛素值进行比较，同时与之前获得的血压正常和高血压的NIDDM患者（n = 32）及正常对照受试者（n = 35）的心脏结构指标进行比较。
与对照受试者相比，血压正常的NIDDM受试者的Cai水平较高（31.5±2.3对24.3±1.9 nmol/L，P = 0.05），细胞内游离镁（Mgi）水平较低（200±10对225±7 μmol/L，P = 0.05），后壁厚度更大（0.98±0.04对0.86±0.03 cm，P = 0.05）。高血压的NIDDM受试者的Cai（43.1±4.4 nmol/L，与对照受试者相比P = 0.05）和左心室质量（LVM）（201.5±12.2对¬155.8±7.7 g，与对照受试者相比P = 0.05）进一步升高。对于所有受试者，观察到Cai与空腹血糖（r = 0.510，P < 0.01）、糖化血红蛋白（HbAic）（r = 0.389，P < 0.05）以及对OGTT的血糖反应（葡萄糖曲线下面积[AUC]；r = 0.519，P < 0.01）和收缩压（r = 0.504，P <¬0.01）及舒张压（r = 0.624，P < 0.01）之间存在显著相关性。左心室质量指数（LVMI）与空腹血糖水平（r = 0.406，P < 0.01）和葡萄糖AUC（r = 0.380，P < 0.01）相关，但与空腹胰岛素或对OGTT的胰岛素反应无关。LVMI与Cai的相关性最佳（r = 0.516，P < 0.01），而与Caio呈负相关（r = -0.486，P < 0.01）。多变量回归表明，葡萄糖对LVMI的影响独立于年龄、体重指数、胰岛素和血压，但与Cai存在显著相互作用。
总体而言，这些数据表明，与葡萄糖相关的过量Cai是糖尿病中的一种基本病变，它导致了该疾病中血压升高和心脏质量增加。
