Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK.
Human Nutrition and Exercise Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Diabetologia. 2024 Nov;67(11):2555-2567. doi: 10.1007/s00125-024-06249-7. Epub 2024 Aug 13.
AIMS/HYPOTHESIS: The temporal suppression of insulin clearance after glucose ingestion is a key determinant of glucose tolerance for people without type 2 diabetes. Whether similar adaptations are observed after the ingestion of a mixed-macronutrient meal is unclear.
In a secondary analysis of data derived from two randomised, controlled trials, we studied the temporal responses of insulin clearance after the ingestion of a standardised breakfast meal consisting of cereal and milk in lean normoglycaemic individuals (n=12; Lean-NGT), normoglycaemic individuals with central obesity (n=11; Obese-NGT) and in people with type 2 diabetes (n=19). Pre-hepatic insulin secretion rates were determined by the deconvolution of C-peptide, and insulin clearance was calculated using a single-pool model. Insulin sensitivity was measured by an oral minimal model.
There were divergent time course changes in insulin clearance between groups. In the Lean-NGT group, there was an immediate post-meal increase in insulin clearance compared with pre-meal values (p<0.05), whereas insulin clearance remained stable at baseline values in Obese-NGT or declined slightly in the type 2 diabetes group (p<0.05). The mean AUC for insulin clearance during the test was 40% lower in the Obese-NGT (1.3 ± 0.4 l min m) and type 2 diabetes (1.4 ± 0.7 l min m) groups compared with Lean-NGT (1.9 ± 0.5 l min m; p<0.01), with no difference between the Obese-NGT and type 2 diabetes groups. HOMA-IR and glucagon AUC emerged as predictors of insulin clearance AUC, independent of BMI, age or insulin sensitivity (adjusted R=0.670). Individuals with increased glucagon AUC had a 40% reduction in insulin clearance AUC ( -0.75 l min m; p<0.001).
CONCLUSIONS/INTERPRETATION: The ingestion of a mixed-macronutrient meal augments differing temporal profiles in insulin clearance among individuals without type 2 diabetes, which is associated with HOMA-IR and the secretion of glucagon. Further research investigating the role of hepatic glucagon signalling in postprandial insulin kinetics is warranted.
ISRCTN17563146 and ISRCTN95281775.
目的/假设：在没有 2 型糖尿病的人群中，葡萄糖摄入后胰岛素清除的暂时抑制是葡萄糖耐量的关键决定因素。摄入混合宏量营养素餐后是否会出现类似的适应性尚不清楚。
在两项随机对照试验数据的二次分析中，我们研究了 lean normoglycaemic 个体（Lean-NGT，n=12）、伴中心性肥胖的 normoglycaemic 个体（Obese-NGT，n=11）和 2 型糖尿病患者（type 2 diabetes，T2D，n=19）在摄入标准早餐（包括麦片和牛奶）后胰岛素清除的暂时反应。通过 C 肽反卷积测定肝前胰岛素分泌率，并使用单池模型计算胰岛素清除率。通过口服最小模型测定胰岛素敏感性。
各组之间胰岛素清除的时间进程变化存在差异。在 Lean-NGT 组中，与餐前值相比，餐后即刻胰岛素清除率增加（p<0.05），而 Obese-NGT 组胰岛素清除率保持在基线值稳定，T2D 组略有下降（p<0.05）。Obese-NGT（1.3±0.4 l min m）和 T2D（1.4±0.7 l min m）组测试期间胰岛素清除的 AUC 平均值比 Lean-NGT 组低约 40%（1.9±0.5 l min m；p<0.01），Obese-NGT 组与 T2D 组之间无差异。HOMA-IR 和胰高血糖素 AUC 是胰岛素清除 AUC 的独立预测因素，与 BMI、年龄或胰岛素敏感性无关（调整后的 R=0.670）。胰高血糖素 AUC 升高的个体胰岛素清除 AUC 降低 40%（~-0.75 l min m；p<0.001）。
结论/解释：摄入混合宏量营养素餐后，在没有 2 型糖尿病的个体中，胰岛素清除呈现出不同的时间模式，这与 HOMA-IR 和胰高血糖素的分泌有关。进一步研究肝源性胰高血糖素信号在餐后胰岛素动力学中的作用是必要的。
ISRCTN80363309 和 ISRCTN95281775。
