Maccario M, Oleandri S E, Avogadri E, Rossetto R, Grottoli S, Procopio M, Camanni F, Ghigo E
Dipartimento di Medicina Interna, Università di Torino, Italy.
J Endocrinol Invest. 1998 Jan;21(1):56-63. doi: 10.1007/BF03347287.
It is widely accepted that abdominal obesity presents with exaggerated insulin secretion, insulin resistance and a trend toward glucose intolerance. Hypertension is frequently associated to abdominal obesity, and hyperinsulinism could play a role in its pathogenesis. Some studies reported that Ca-antagonists positively influence insulin sensitivity and glucose tolerance in obese patients with normal or elevated blood pressure. However, other studies reported worsening of metabolic balance during treatment with Ca-antagonists in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients and in normal subjects. We studied 19 patients with abdominal obesity, mild hypertension and insulin resistance on balanced, mild hypocaloric diet (1400 Kcal), to verify the effects of the Ca-antagonist nifedipine on both basal and oral glucose tolerance test (OGTT)-induced glucose and insulin levels as well as on IGF-I basal and DHEA-S levels and fat mass (FM). To achieve this goal, 10 hypertensive obese subjects (HOB-NIFE, 3 males, 7 females, mean age +/- SD 44.6 +/- 1.7 yr; body mass index (BMI) 37.1 +/- 2.5 Kg/m2, WHR 0.95 +/- 0.02) received 3-month treatment with nifedipine (Adalat Crono 30 Bayer, 1 tab daily) while other 9 hypertensive obese (HOB, 3 males, 6 females, 42 +/- 2.4 yr, BMI 35.8 +/- 1.8 Kg/m2, WHR 0.91 +/- 0.03) were studied during diet only. The same parameters were studied also in 8 normotensive obese patients (OB: 3 males, 5 females, 48.1 +/- 2.1 yr, BMI 35.8 +/- 2.4 Kg/m2, WHR 0.90 +/- 0.03) on the same balanced hypocaloric diet. Basal systolic (SBP) and diastolic (DBP) blood pressure levels in HOB-NIFE and HOB were similar. At baseline, all groups had similar basal and OGTT-induced glucose, insulin and glucose insulin ratio (GIR) levels as well as IGF-I and DHEA-S levels. After 3 months BMI fell to the same extent in all groups (p < 0.05 vs baseline) while WHR and FFM/FM ratio did not change. SBP and DBP decreased HOB-NIFE (p < 0.02) but also during diet alone in both HOB and OB, though to a lesser extent (p < 0.05). Both basal and OGTT-stimulated glucose and insulin levels as well as IGF-I and DHEA-S levels were not modified in HOB-NIFE as well as in HOB and OB. In conclusion, our data indicate that nifedipine treatment does not modify glucose tolerance as well as insulin secretion and sensitivity, IGF-I and DHEA-S levels in hypertensive abdominal obese patients. Thus, nifedipine treatment has no detrimental effects on endocrine-metabolic balance in hypertensive obese patients.
普遍认为，腹型肥胖表现为胰岛素分泌过度、胰岛素抵抗以及糖耐量异常的趋势。高血压常与腹型肥胖相关，高胰岛素血症可能在其发病机制中起作用。一些研究报告称，钙拮抗剂对血压正常或升高的肥胖患者的胰岛素敏感性和糖耐量有积极影响。然而，其他研究报告称，在高血压非胰岛素依赖型糖尿病（NIDDM）患者和正常受试者中，使用钙拮抗剂治疗期间代谢平衡会恶化。我们研究了19例腹型肥胖、轻度高血压和胰岛素抵抗的患者，他们采用均衡、轻度低热量饮食（1400千卡），以验证钙拮抗剂硝苯地平对基础和口服葡萄糖耐量试验（OGTT）诱导的血糖和胰岛素水平以及IGF-I基础水平、脱氢表雄酮硫酸盐（DHEA-S）水平和脂肪量（FM）的影响。为实现这一目标，10例高血压肥胖受试者（HOB-NIFE，3例男性，7例女性，平均年龄±标准差44.6±1.7岁；体重指数（BMI）37.1±2.5kg/m2，腰臀比（WHR）0.95±0.02）接受了3个月的硝苯地平治疗（拜耳公司的拜新同30，每日1片），而另外9例高血压肥胖患者（HOB，3例男性，6例女性，42±2.4岁，BMI 35.8±1.8kg/m2，WHR 0.91±0.03）仅在饮食期间接受研究。8例血压正常的肥胖患者（OB：3例男性，5例女性，48.1±2.1岁，BMI 35.8±2.4kg/m2，WHR 0.90±0.03）在相同的均衡低热量饮食下也进行了相同参数的研究。HOB-NIFE和HOB的基础收缩压（SBP）和舒张压（DBP）水平相似。基线时，所有组的基础和OGTT诱导的血糖、胰岛素和葡萄糖胰岛素比值（GIR）水平以及IGF-I和DHEA-S水平相似。3个月后，所有组的BMI均下降至相同程度（与基线相比，p<0.05），而WHR和去脂体重/脂肪量比值未改变。HOB-NIFE组的SBP和DBP下降（p<0.02），但HOB组和OB组仅在饮食期间血压也下降，尽管下降程度较小（p<0.05）。HOB-NIFE组以及HOB组和OB组的基础和OGTT刺激的血糖和胰岛素水平以及IGF-I和DHEA-S水平均未改变。总之，我们的数据表明，硝苯地平治疗不会改变高血压腹型肥胖患者的糖耐量以及胰岛素分泌和敏感性、IGF-I和DHEA-S水平。因此，硝苯地平治疗对高血压肥胖患者的内分泌代谢平衡没有不利影响。
