Postprandial lipaemia induces an acute decrease of insulin sensitivity in healthy men independently of plasma NEFA levels

Abstract

Aims/hypothesis: Typical Western diets cause postprandial lipaemia for 18 h per day. We tested the hypothesis that postprandial lipaemia decreases insulin sensitivity. Subjects, materials and methods: Employing a randomised crossover design, we administered two types of virtually isocaloric meals to ten healthy volunteers on two separate occasions. The meals (Meals 1 and 2) were both designed to produce a rise in triglycerides, but only Meal 1 generated a rise in NEFA, too. Insulin sensitivity, as quantified by an IVGTT with minimal model analysis, was calculated postabsorptively at 08.00 h and postprandially at 13.00 h, i.e. 3 h after meal ingestion. Results: Triglycerides rose from 0.91±0.31 mmol/l postabsorptively to 2.08±0.70 mmol/l postprandially with Meal 1 (p=0.005) and from 0.92±0.41 to 1.71±0.79 mmol/ l with Meal 2 (p=0.005). Neither the triglyceride levels at 13.00 h, nor the post-meal AUCs for triglycerides were statistically different between Meal 1 and Meal 2. NEFA rose from 0.44±0.17 mmol/l postabsorptively to 0.69±0.16 mmol/ l postprandially with Meal 1 (p=0.005) and showed no significant change with Meal 2 (0.46±0.31 mmol/l postabsorptively vs 0.36±0.32 mmol/l postprandially, p=0.09). Both the NEFA level at 13.00 h and the post-meal AUC for NEFA were significantly higher after Meal 1 than Meal 2. Compared with the postabsorptive state, insulin sensitivity decreased postprandially after each of the two meals to a comparable degree (Meal 1: −53%, p=0.02; Meal 2: −45%, p=0.005). Conclusions/interpretation: Our study reveals a drop in insulin sensitivity during postprandial lipaemia and strongly suggests that decreased insulin sensitivity is brought about by elevated plasma levels of triglyceride-rich lipoproteins independently of plasma NEFA levels.

Effects of meals rich in either monounsaturated or saturated fat on lipid concentrations and on insulin secretion and action in subjects with high fasting triglyceride concentrations

“…Postprandial studies previously showed the potential of highfat meals to induce b cell dysfunction and insulin resistance in healthy individuals (4,8) and in subjects with type 2 diabetes (15) or the metabolic syndrome (16). In addition, Monnier et al (17) found that the evolution of type 2 diabetes is related to the progressive deterioration of glucose homeostasis that starts during the postprandial period in subjects whose glycemic profiles are normal at fasting.…”

“…The Third Report of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) (2) has advised the use of lower cutoffs for the categorization of fasting triglycerides than the ATP II guidelines (3), which reflects a growing awareness of the importance of even moderate increases in triglyceride concentrations. Recently, it was postulated that insulin resistance might also be involved in the acute metabolism of dietary fats (4). Exaggerated nonfasting concentrations of triglycerides, via higher peak concentrations or delayed clearance, is an inherent feature of diabetic dyslipidemia and is frequently found even in diabetic patients with normal fasting triglycerides (5).…”

Point: HOMA—Satisfactory for the Time Being

“…These modifications include the infusion of tolbutamide to trigger a pancreatic response, an injection of insulin 20 min after glucose administration, the addition of glucose tracers to separate the effects of glucose production and utilization, and several different methods to enhance the minimal model (13)(14)(15). Overall, its use is limited to small research studies as an alternative to the euglycemic insulin clamp (16,17).…”

Mixed Meal Model in Type 1 Diabetes

“…Considering that the maximum postprandial increase in TG levels is IR T,max = 1 mmol/L after a very large fat load in patients with T1DM [19], and the maximum reduction in insulin sensitivity due to postprandial increase in TG levels is one-half [20], we set parameter p 8 = p 30 /2 in eq. (12).…”