肥胖对正常人和非胰岛素依赖型糖尿病患者胰岛素抵抗的影响。

Effect of obesity on insulin resistance in normal subjects and patients with NIDDM.

作者信息

Ludvik B, Nolan J J, Baloga J, Sacks D, Olefsky J

机构信息

Department of Medicine, University of California, San Diego, USA.

出版信息

Diabetes. 1995 Sep;44(9):1121-5. doi: 10.2337/diab.44.9.1121.

DOI:10.2337/diab.44.9.1121

PMID:7657038

Abstract

Insulin resistance (IR) is a characteristic feature of non-insulin-dependent diabetes mellitus (NIDDM) as well as obesity, and a majority of NIDDM patients are obese. To assess the effect of obesity independent of NIDDM on IR, we studied the relationship between IR and obesity in 65 normal and 58 NIDDM subjects; we used body mass index (BMI) as a measure of obesity and glucose infusion rate (GINF) during a euglycemic hyperinsulinemic (120 mU.m-2.min-1) glucose clamp as a measure of IR. In lean normal subjects, GINF was 57.7 +/- 2.2 mumol.kg-1.min-1 (10.4 +/- 0.4 mg.kg-1.min-1) and the lean NIDDM subjects were markedly insulin-resistant, with a GINF of 34.4 +/- 2.8 mumol.kg-1.min-1 (6.2 +/- 0.5 mg.kg-1.min-1). Obese normal subjects were also insulin-resistant compared with lean normal subjects, with a GINF of 36.1 +/- 2.2 mumol.kg-1.min-1 (6.5 +/- 0.4 mg.kg-1.min-1), and obesity caused an increase in IR in NIDDM, with a GINF of 21.1 +/- 1.4 mumol.kg-1.min-1 (3.8 +/- 0.25 mg.kg-1.min-1) in the obese NIDDM subjects. Therefore, approximately 61% of the IR in obese NIDDM subjects is due to NIDDM, with 39% due to obesity, demonstrating a greater impact of NIDDM than of obesity in causing IR. The correlation between GINF and BMI was much better in normal subjects (r = -0.75) than in NIDDM subjects (r = -0.50) as was the relationship between fasting insulin level and BMI (r = -0.59 in normal subjects, r = -0.48 in NIDDM subjects). As expected, the fasting insulin level was also strongly correlated to GINF in normal subjects (r = -0.61); however, this relationship was weaker in NIDDM subjects ( r = -0.46). In conclusion, 1) obesity has a major impact to cause insulin resistance in nondiabetic subjects, but the effect of obesity on IR in NIDDM is less; 2) NIDDM per se is the major contributor to IR in NIDDM; and 3) the fasting insulin level is a better surrogate marker of IR in nondiabetic subjects than in NIDDM patients.

摘要

胰岛素抵抗（IR）是非胰岛素依赖型糖尿病（NIDDM）以及肥胖症的一个特征，并且大多数NIDDM患者都肥胖。为了评估独立于NIDDM的肥胖对IR的影响，我们研究了65名正常人和58名NIDDM患者中IR与肥胖之间的关系；我们使用体重指数（BMI）作为肥胖的衡量指标，并在正常血糖高胰岛素血症（120 mU·m⁻²·min⁻¹）葡萄糖钳夹期间的葡萄糖输注率（GINF）作为IR的衡量指标。在体型瘦的正常受试者中，GINF为57.7±2.2 μmol·kg⁻¹·min⁻¹（10.4±0.4 mg·kg⁻¹·min⁻¹），而体型瘦的NIDDM受试者明显存在胰岛素抵抗，GINF为34.4±2.8 μmol·kg⁻¹·min⁻¹（6.2±0.5 mg·kg⁻¹·min⁻¹）。与体型瘦的正常受试者相比，肥胖的正常受试者也存在胰岛素抵抗，GINF为36.1±2.2 μmol·kg⁻¹·min⁻¹（6.5±0.4 mg·kg⁻¹·min⁻¹），并且肥胖导致NIDDM患者的IR增加，肥胖的NIDDM受试者的GINF为21.1±1.4 μmol·kg⁻¹·min⁻¹（3.8±0.25 mg·kg⁻¹·min⁻¹）。因此，肥胖的NIDDM受试者中约61%的IR是由NIDDM引起的，39%是由肥胖引起的，这表明NIDDM在导致IR方面比肥胖的影响更大。正常受试者中GINF与BMI之间的相关性（r = -0.75）比NIDDM受试者中更好（r = -0.50），空腹胰岛素水平与BMI之间的关系也是如此（正常受试者中r = -0.59，NIDDM受试者中r = -0.48）。正如预期的那样，正常受试者中空腹胰岛素水平也与GINF密切相关（r = -0.61）；然而，这种关系在NIDDM受试者中较弱（r = -0.46）。总之，1）肥胖对非糖尿病受试者的胰岛素抵抗有重大影响，但肥胖对NIDDM患者IR的影响较小；2）NIDDM本身是NIDDM患者IR的主要促成因素；3）空腹胰岛素水平在非糖尿病受试者中比在NIDDM患者中是更好的IR替代指标。