Fatty acids modulate cytokine and chemokine secretion of stimulated human whole blood cultures in diabetes.

Fatty acids, uric acid and glucose are thought to contribute to subclinical inflammation associated with diabetes mellitus. We tested whether co-incubation of free fatty acids and uric acid or glucose influences the secretion of immune mediators from stimulated human whole blood in vitro. Fresh whole blood samples from 20 healthy subjects, 20 patients with type 1 diabetes and 23 patients with type 2 diabetes were incubated for 24 h with palmitic acid (PAL), linolenic acid (LIN) or eicosapentaenoic acid (EPA) alone or together with elevated concentrations of uric acid or glucose. Concentrations of proinflammatory cytokines interleukin (IL)-1ß, IL-2, IL-12(p70), IL-18, IFN-γ, of regulatory cytokines IL-4, IL-10, IL-17 and chemokine CCL2 (MCP-1) were measured by multiplex-bead technology from supernatants. Co-incubation of fatty acids with uric acid resulted in a significant reduction of IL-10, IL-12(p70), IFN-γ and CCL2 (MCP-1) concentrations in supernatants compared to incubation with uric acid alone (P < 0·0001). In contrast, IL-18 was up-regulated upon co-stimulation with fatty acids and uric acid. Similarly, co-incubation of fatty acids with glucose diminished secretion of IL-10, IFN-γ and CCL2 (monocyte chemotactic protein-1), while IL-8 was up-regulated (P < 0·001). Samples from healthy and diabetic subjects did not differ after adjustment for age, sex, body mass index and diabetes type. All three fatty acids similarly influenced whole blood cytokine release in vitro and modulated uric acid or glucose-stimulated cytokine secretion. Although the ω-3-fatty acid EPA showed slightly stronger effects, further studies are required to elaborate the differential effects of PAL, LIN and EPA on disease risk observed previously in epidemiological studies.

Differences in trends in estimated incidence of myocardial infarction in non-diabetic and diabetic people: Monitoring Trends and Determinants on Cardiovascular Diseases (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) registry.

AIMS/HYPOTHESIS: One major objective of the St Vincent Declaration was to reduce the excess risk of myocardial infarction in patients with diabetes mellitus. We estimated the trend of the incidence and relative risk of myocardial infarction in the diabetic and non-diabetic populations in southern Germany from 1985 to 2006. METHODS: Using data from the Monitoring Trends and Determinants on Cardiovascular Diseases (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) Project in southern Germany, we ascertained all fatal and non-fatal first myocardial infarctions between 1985 and 2006 (n = 14,891, age 25-74 years). We estimated the diabetic and the non-diabetic populations using data on diabetes prevalence from surveys, and evaluated incidence of myocardial infarction in the two estimated populations. To test for time trends, we fitted Poisson regression models. RESULTS: Of individuals with first myocardial infarction, 71% were male and 28% known to have diabetes. In the non-diabetic population, myocardial infarction incidence decreased by about 1.5% to 2.0% per year. A comparable decrease was seen in the population of diabetic women. However, in the population of diabetic men, incidence of myocardial infarction increased by about 1% per year. Over the whole study period, myocardial infarction incidence decreased by 34% and 27% in non-diabetic men and women respectively (RR 0.66, 95% CI 0.59-0.74 and 0.73, 0.62-0.87 respectively). In diabetic women, it decreased by 27% (RR 0.73, 0.61-0.88), whereas in diabetic men, it increased by 25% (RR 1.25, 1.07-1.45). CONCLUSIONS/INTERPRETATION: Our results suggest that the St Vincent goal of reducing excess cardiovascular morbidity in diabetic individuals has not been achieved and that the situation in men has actually got worse.