Monocytes, but not T cells, respond to insulin with Akt(S473) phosphorylation independent of the donor glucometabolic state.

BACKGROUND: Obesity is associated with insulin resistance and chronic low-grade inflammation. Insulin has been described to have anti-inflammatory effects in immune cells. Therefore, insulin resistance in immune cells can be expected to have important consequences for immune function. Here, we investigate whether freshly isolated monocytes and T cells, isolated from study subjects with a normal or disturbed glucometabolic state, respond to insulin with phosphorylation of Akt, a key molecule in the insulin signalling pathway. METHODS: A total of 25 study subjects were enrolled in the study. An oral glucose tolerance test (OGTT) was performed, and from fasting insulin and glucose, the homeostasis model assessment of insulin resistance (HOMA-IR) index was calculated. Peripheral blood mononuclear cells were isolated from heparinized blood and phenotypically characterized by flow cytometry. Basal and insulin-induced fractions of pAkt(S473)-positive monocytes and T cells were determined by Phosflow. RESULTS: On the basis of the OGTT, 11 subjects were classified as normal glucose tolerant (NGT), 9 had an impaired glucose metabolism (IGM) and 5 had type 2 diabetes (T2DM). The fraction of pAkt(S473)positive-T cells and monocytes, in the absence of insulin, was low in all subjects. Incubation with insulin did not induce Akt phosphorylation in CD4⁺ and CD8⁺ T cells in normal subjects. However, in the monocyte fraction, an insulin-dose-dependent increase of the pAkt(S473)positive-cell fraction was observed. This response did not differ between NGT, IGM and T2DM and was not correlated with HOMA-IR. CONCLUSIONS: In this study, we show that freshly isolated monocytes, but not T cells, are insulin-sensitive cells and that this insulin sensitivity of monocytes is not negatively affected by the glucometabolic state of the donor.

Prevention of the metabolic syndrome in IGT subjects in a lifestyle intervention: results from the SLIM study.

BACKGROUND AND AIMS: The Study on Lifestyle intervention and Impaired glucose tolerance Maastricht (SLIM), a randomized controlled trial, directed at diet and physical activity in impaired glucose tolerant subjects was effective to improve glucose tolerance and prevent type 2 diabetes. The aim of this study was to determine the effects of the SLIM lifestyle intervention on the incidence and prevalence of the metabolic syndrome (MetS) during the active intervention and four years thereafter. METHODS AND RESULTS: MetS was diagnosed according to the NCEP ATP III criteria. At baseline, 66.4% of all participants (n = 146, age 57 ± 7 years, BMI 29.7 ± 3.6, 51.3% female) fulfilled the criteria for MetS. No significant difference in MetS prevalence was observed between the intervention (63.9%) and control group (68.9%). At the end of active intervention (average duration 4.2 ± 2.0 years), prevalence of MetS was significantly lower in the intervention group (52.6%, n = 57) compared to the control group (74.6%, n = 59) (p = 0.014). Furthermore, in participants without MetS at baseline, cumulative incidence of MetS was 18.2% in the intervention group at the end of active intervention, compared to 73.7% in the control group (Log-rank test, p = 0.011). Four years after stopping active intervention, the reduced incidence of MetS was maintained (Log-rank test, p = 0.002). CONCLUSION: In conclusion, a combined diet-and-exercise intervention to improve glucose tolerance, not only prevented type 2 diabetes, but also reduced the prevalence of MetS and prevented MetS development, showing the long-term impact of lifestyle intervention on cardiovascular risk reduction.