Mingrone G, DeGaetano A, Greco A V, Capristo E, Benedetti G, Castagneto M, Gasbarrini G
Istituto di Medicina Interna e Geriatria, Università Cattolica S. Cuore, Rome, Italy.
Diabetologia. 1997 May;40(5):599-605. doi: 10.1007/s001250050721.
The aim of the present study was to measure whole body glucose uptake (M) and oxidation rate by euglycaemic hyperinsulinaemic clamp and indirect calorimetry in 7 morbidly obese subjects (BMI > 40 kg/m2) at three time points: before bilio-pancreatic diversion (BPD) surgery (Ob); 3 months after surgery POI; and after reaching stable body weight, at least 2 years after surgery POII. A group of 7 control subjects (C), matched groupwise for sex, age and BMI with POII patients, was also studied. The M value at POI was significantly higher than at Ob (49.12 +/- 8.57 vs 18.14 +/- 8.57 mumol.kg-1.min-1). No statistical difference was observed between the POII and C groups. Similarly, glucose oxidation rate was significantly increased at POI with respect to Ob (24.2 +/- 7.23 vs 9.42 +/- 3.91 mumol.kg-1.min-1) and was not significantly different between POII and C. Basal levels of non-esterified fatty acids (NEFA) decreased significantly both from Ob to POI and from POI to POII (1517.1 +/- 223.9 vs 1039.6 +/- 283.4 vs 616.0 +/- 77.6 mumol.1(-1). The same applied to basal plasma triglycerides (2.07 +/- 0.77 vs 1.36 +/- 0.49 vs 0.80 +/- 0.19 g.1(-1). Weight decreased mainly in the late postoperative period (POI to POII 124.28 +/- 11.22 to 69.71 +/- 11.78, 83% of total decrement), rather than in the early postoperative period (Ob to POI 135.25 +/- 14.99 to 124.28 +/- 11.22 kg, 17% of total decrement). We also report the clinical case of a young woman of normal weight, who underwent BPD for chylomicronaemia (secondary to familial lipoprotein lipase deficiency), whose M value, plasma insulin and blood glucose levels were normalized upon normalization of serum NEFA and triglyceride levels as determined by the therapeutic lipid malabsorption. In conclusion, in obese diabetic patients lipid malabsorption induced by BPD causes a definite enhancement of insulin sensitivity and glucose tolerance. This improvement in metabolism is noticeable before the surgery has major effects on body weight. These observations suggest that lowered plasma lipids, rather than weight loss per se, are the cause of the reversibility of insulin resistance.
本研究的目的是通过正常血糖高胰岛素钳夹技术和间接测热法，在7例病态肥胖受试者（BMI>40kg/m²）的三个时间点测量全身葡萄糖摄取量（M）和氧化率：胆胰转流术（BPD）手术前（Ob）；术后3个月（POI）；术后达到稳定体重后，至少在术后2年（POII）。还研究了一组7例对照受试者（C），其在性别、年龄和BMI方面与POII患者进行了分组匹配。POI时的M值显著高于Ob时（49.12±8.57对18.14±8.57μmol·kg⁻¹·min⁻¹）。POII组和C组之间未观察到统计学差异。同样，与Ob相比，POI时葡萄糖氧化率显著增加（24.2±7.23对9.42±3.91μmol·kg⁻¹·min⁻¹），POII组和C组之间无显著差异。非酯化脂肪酸（NEFA）的基础水平从Ob到POI以及从POI到POII均显著降低（1517.1±223.9对1039.6±283.4对616.0±77.6μmol·L⁻¹）。基础血浆甘油三酯情况也是如此（2.07±0.77对1.36±0.49对0.80±0.19g·L⁻¹）。体重下降主要发生在术后晚期（从POI到POII，从124.28±11.22降至69.71±11.78kg，占总下降量的83%），而非术后早期（从Ob到POI，从135.25±14.99降至124.28±11.22kg，占总下降量的17%）。我们还报告了一例体重正常的年轻女性的临床病例，她因乳糜微粒血症（继发于家族性脂蛋白脂肪酶缺乏）接受了BPD手术，随着治疗性脂质吸收不良导致血清NEFA和甘油三酯水平正常化，其M值、血浆胰岛素和血糖水平也恢复正常。总之，在肥胖糖尿病患者中，BPD诱导的脂质吸收不良导致胰岛素敏感性和葡萄糖耐量明显增强。这种代谢改善在手术对体重产生重大影响之前就很明显。这些观察结果表明，血浆脂质降低而非体重减轻本身是胰岛素抵抗可逆性的原因。
