Effects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cytokines in patients with mixed hyperlipidemia and impaired fasting glucose.

OBJECTIVE: Concerns regarding worsening insulin sensitivity associated with statin treatment have recently emerged. Therefore the aim of this study was to assess and compare the effects of 90-day monotherapies with fenofibrate and atorvastatin, as well as combined therapy, on fasting plasma glucose, insulin resistance index, adipokines (leptin, resistin, adiponectin) and levels of proinflammatory cytokines (TNF-α, IL-6) in patients with impaired fasting glucose (IFG) and mixed hyperlipidemia. MATERIALS AND METHODS: 67 patients were randomly assigned to four treatment arms: monotherapy with atorvastatin, monotherapy with fenofibrate, combined therapy (fenofibrate and torvastatin) or therapeutic lifestyle change. The study lasted for 90 days. All participants received counseling regarding proper diet and physical activity. RESULTS: Compared to the control subjects, prediabetic patients exhibited elevated plasma levels of leptin, resistin, TNF-α and IL-6, and a lower plasma level of adiponectin. All therapeutic interventions resulted in significant alterations in the lipid profile. Insulin resistance index (HOMA-IR) was reduced after treatment with fenofibrate. The effect of atorvastatin on insulin resistance was comparable to therapeutic lifestyle change alone. Therapy with hypolipidemic drugs caused increases in adiponectin levels and decreases in leptin and resistin. An additive effect of the combined treatment on plasma IL-6 level was also observed. CONCLUSIONS: Fenofibrate-based treatment was associated with improved insulin sensitivity. Atorvastatin did not cause a deterioration in insulin sensitivity. Hypolipidemic therapies resulted in significant changes in the proinflammatory cytokine network as well as in adipokine levels. At the end of the study the measured parameters nearly resembled those of the healthy subjects.

[Immune reactivity in patients with disorders of lipid metabolism]. / Immunreaktivität bei Patienten mit Fettstoffwechselstörungen.

The accidental observation of a selective IgM-deficit in a family with hyperlipoproteinaemia type II caused the working hypothese of close interactions of lipometabolism and immunoreactivity. In 69 patients with hyperlipoproteinaemia the quantitative determination of the immunoglobulins G, A and M was performed by the Mancini-test. All decreased values were repeated in a second determination at another moment. In 9 patients with hyperlipoproteinaemia and deficit of immunoglobulins we determined the T-lymphocytes by means of the sheep erythrocyte rosette test, the B-lymphocytes with the help of the method of direct immunofluorescence and the mouse erythrocyte rosette test. Altogether 14 of the 69 patients with hyperlipoproteinaemia showed reproducible deficit of immunoglobulins, which is statistically significant. The immune defect appeared above all as decrease of IgA (11 patients) isolated 8 patients or in combination with IgM-deficit (2 patients) and IgG-deficit (1 patient). 2 resp. 1 patient showed selective IgG- or IgM-deficit. Clinical symptoms of an immune defect were not recognizable anamnestically and prospectively. In the 9 patients who were immunologically further characterized the T-lymphocytes were in the region of the norm or were increased, the subpopulation of B-lymphocytes which reacted with mouse erythrocytes was normal or increased. The classification to the types of hyperlipoproteinaemia of the altogether 14 deficient patients showed the order IIa, IV, IIb. The original working hypothesis could be supported by the present findings, though an obvious clinical importance is not yet to be recognized. Changes of the membrane lipids of lymphocytes, interventions through the prostaglandin system and effect via suppressor cells must be discussed causally.