Kriketos A, Milner K-L, Denyer G, Campbell L
Diabetes and Obesity Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Sydney, NSW 2010, Australia.
Eur J Clin Invest. 2005 Feb;35(2):117-25. doi: 10.1111/j.1365-2362.2005.01458.x.
Higher postprandial triglyceride responses reported in first degree relatives of people with type 2 diabetes (REL) were postulated to be the result of an early, possibly intrinsic, defect in oral lipid handling. The postprandial triglyceride response to high fat meals (HFM) in normal subjects is reduced by the insulin response to dietary carbohydrate (CHO) in the meal. The aims of this study were to examine whether (1) insulin resistance is associated with an intrinsic defect in triglyceride handling in insulin-resistant REL and (2) insulin resistance is associated with altered triglyceride handling after HFM with high CHO content.
Postprandial responses to a HFM in normolipidaemic, normoglycaemic REL were compared with subjects without a family history of diabetes mellitus (CON). Over 6 h, the insulin, glucose, triglyceride and nonesterified fatty acid (NEFA) responses after a high fat (80 g fat), low CHO (HFM-LC; 20 g CHO, 4250 kJ) meal and a high fat, high CHO (HFM-HC; 100 g CHO, 5450 kJ) meal were examined.
The 10 (7F/3M) REL were significantly more insulin-resistant, determined by glucose infusion during a hyperinsulinaemic euglycaemic clamp than the 10 (5F/5M) CON (glucose infusion rate 44.6 +/- 4.9 vs. 60.0 +/- 4.8 micromol min(-1) kg FFM(-1), P = 0.037). Subjects were similar for age and body mass index (BMI). The triglyceride increments after the HFM-LC were similar in both, peaking at 180-240 min (Delta0.77 +/- 0.11 mmol L(-1)), demonstrating no postprandial defect in REL, despite insulin resistance. There was a significantly lower postprandial triglyceride response in CON following the HFM-HC compared with the HFM-LC, but not in REL. In contrast, the higher insulin level during the HFM-HC was associated with significantly greater NEFA level suppression than in the HFM-LC (2.13 +/- 0.51 vs. 0.70 +/- 0.35 mmol L(-1), P = 0.03), only in the REL.
These results are inconsistent with a primary aetiological role for postprandial hypertriglyceridaemia in already insulin resistant type 2 diabetic REL, but raise the possibility that this potentially atherogenic manifestation is secondary to insulin resistance lessening VLDL production and/or release from the liver.
2型糖尿病患者的一级亲属（REL）餐后甘油三酯反应较高，据推测这是由于口服脂质处理早期可能存在的内在缺陷所致。正常受试者对高脂肪餐（HFM）的餐后甘油三酯反应会因餐中碳水化合物（CHO）引发的胰岛素反应而降低。本研究的目的是探讨：（1）胰岛素抵抗是否与胰岛素抵抗的REL中甘油三酯处理的内在缺陷相关；（2）胰岛素抵抗是否与高CHO含量的HFM后甘油三酯处理改变相关。
将血脂正常、血糖正常的REL对HFM的餐后反应与无糖尿病家族史的受试者（CON）进行比较。在6小时内，检测了高脂肪（80克脂肪）、低CHO（HFM-LC；20克CHO，4250千焦）餐和高脂肪、高CHO（HFM-HC；100克CHO，5450千焦）餐后的胰岛素、葡萄糖、甘油三酯和非酯化脂肪酸（NEFA）反应。
通过高胰岛素正常血糖钳夹期间的葡萄糖输注测定，10名（7名女性/3名男性）REL的胰岛素抵抗明显高于10名（5名女性/5名男性）CON（葡萄糖输注速率分别为44.6±4.9与60.0±4.8微摩尔·分钟-1·千克去脂体重-1，P = 0.037）。两组受试者的年龄和体重指数（BMI）相似。HFM-LC后的甘油三酯增量在两组中相似，在180 - 240分钟达到峰值（Δ0.77±0.11毫摩尔·升-1），这表明尽管存在胰岛素抵抗，但REL不存在餐后缺陷。与HFM-LC相比，CON在HFM-HC后的餐后甘油三酯反应明显较低，但REL并非如此。相反，仅在REL中，HFM-HC期间较高的胰岛素水平与NEFA水平的抑制作用明显大于HFM-LC（分别为2.13±0.51与0.70±0.35毫摩尔·升-1，P = 0.03）。
这些结果与餐后高甘油三酯血症在已经存在胰岛素抵抗的2型糖尿病REL中的主要病因学作用不一致，但增加了这种潜在致动脉粥样硬化表现继发于胰岛素抵抗从而减少肝脏极低密度脂蛋白（VLDL）产生和/或释放的可能性。
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