Changes in Circulating Postprandial Proinflammatory Cytokine Concentrations in Diet-Controlled Type 2 Diabetes and the Effect of Ingested Fat

Eighteen patients (7 men and 11 women) with type 2 diabetes who had good glycemic control by diet alone, did not smoke cigarettes or use antioxidant supplements, and did not have hepatic or renal diseases or a history of cardiovascular disease were recruited. Fasted participants were fed three meals in random order and separated by weekly intervals. The meals consisted of 200 g instant mashed potatoes plus two cooked eggs alone or in combination with fat in the form of olive oil or cream (0.6 g/kg body wt) and were consumed at ∼0830 h. Participants were allowed to consume water, but not other beverages or food, and remained seated during the study. Thirteen of the participants volunteered for a follow-up study to test the effect of continued fasting for 2 h instead of receiving a meal. Patients gave written and informed consent and the studies were approved by the Otago Ethics Committee.

Venous blood was taken at baseline, 1, 4, and 6 h after the meals, and serum and EDTA plasma were isolated by low-speed centrifugation at 4°C. Aliquots of serum and plasma were stored at −80°C. Glycated hemoglobin, plasma glucose, plasma insulin, and triglycerides were measured by routine methods using commercial kits (Roche Diagnostics) in the Otago Diagnostic Laboratories, Dunedin Hospital. Plasma IL-6 and TNF-α concentrations were measured in duplicate by high-sensitivity enzyme-linked immunosorbent assay methods using commercial kits (R&D Systems). Plasma free fatty acid (FFA) was measured enzymatically using a commercial kit (Roche Diagnostics). Samples from an individual were measured in the same assay to reduce the effect of interassay variation on plasma insulin, IL-6, TNF-α, and FFA.

Values are mean ± SD unless stated otherwise. Data were log transformed before statistical analysis using the STATA program. A mixed regression model that included a random effect for individuals and adjustment for order was used to analyze the data.

At baseline, mean age, BMI, fasting glucose, and HbA_1c were 61 ± 10 years, 28.5± 4.4 kg/m², 6.8 ± 1.7 mmol/l, and 6.5 ± 0.6%, respectively. Duration of diabetes ranged from 2 to 60 months (mean 22 months).

Plasma glucose and insulin concentrations increased significantly and plasma FFA and IL-6 concentrations decreased significantly 1 h after all the meals and then returned to baseline during the following 5 h (Fig. 1). Plasma TNF-α was significantly lower than baseline at 4 and 6 h after the meals (Fig. 1). Plasma triglyceride concentration increased significantly 4 h after the fatty meals and did not vary significantly (P = 0.19) after the control meal. There was no significant effect of the order in which the meals were received on the IL-6 and TNF-α data.

Plasma IL-6 (P = 0.41), TNF-α (P = 0.93), glucose (P = 0.14), and insulin (P = 0.72) did not change significantly at 1 and 2 h, and plasma FFA tended to increase (P = 0.08) during continued 2-h fasting from 0800 h in the 13 patients (9 women and 4 men) who volunteered for the follow-up study.

Our data suggest that in subjects with diet-controlled type 2 diabetes, ingestion of a meal containing potato starch plus egg with or without added MUFAs and SAFAs may have a temporary anti-inflammatory effect as indicated by decreases in plasma levels of both IL-6 and TNF-α in the hours after the meal. This anti-inflammatory effect may possibly be mediated by the postprandial increase in plasma insulin and the associated decrease in plasma FFA. Previous studies have reported a potent anti-inflammatory effect of insulin (7) and an inflammatory effect of raised FFA (8) in vivo. Our findings are in contrast with the previously reported increase in plasma IL-6 and TNF-α in patients with type 2 diabetes after a fatty meal (5). The factors responsible for these divergent findings are unclear. The patients we studied had less severe diabetes, as indicated by lower HbA_1c and fasting blood glucose, and lower plasma TNF-α concentrations. Also, the experimental meals they consumed were more standardized, with fewer components and test fats from only one source. Furthermore, the participants consumed a control meal that contained all of the components except the test fat so that the effect of the test fat alone could be assessed. Finally, it is conceivable that a postprandial decrease in plasma levels could minimize the interference of IL-6 and possibly TNF-α with insulin signaling at a time when the maximal sensitivity of tissues to insulin is important for the uptake of an increased glucose load.

This study was supported by a Novo Nordisk grant from the New Zealand Society for the Study of Diabetes.