Insulin resistance, endocrine function and adipokines in type 2 diabetes patients at different glycaemic levels:: potential impact for glucotoxicity in vivo

Objective To evaluate the interplay between hyperglycaemia, insulin resistance, hormones and adipokines in patients with type 2 diabetes mellitus (T2DM). Design and methods Ten patients with T2DM with good glycaemic control (G), 10 with poor control (P) and 10 nondiabetic control subjects (C) were matched for sex (M/F 6/4), age and body mass index. A hyperinsulinaemic, euglycaemic clamp was performed and cytokines and endocrine functions, including cortisol axis activity were assessed. Results Patients with diabetes were more insulin resistant than group C, and group P exhibited the highest degree of insulin resistance (P = 0.01, P vs C). Tumour necrosis factor (TNF)-alpha levels were elevated in patients with diabetes (P = 0.05) and group P had the highest levels of fasting serum cortisol (P = 0.05), nonesterified fatty acids (NEFA; P = 0.06) and C-reactive protein (CRP; P = 0.01). Adiponectin levels were lower in the P group. In partial correlation analyses, significant associations were found: glycaemic level (HbA1c) with insulin resistance, TNF-alpha, CRP and basal and ACTH-stimulated cortisol levels, insulin resistance with plasma NEFA, TNF-alpha and stimulated cortisol levels. Conclusion Poor glycaemic control in patients with T2DM was associated with insulin resistance and with elevated TNF-alpha, CRP and basal as well as stimulated cortisol levels. Inflammatory mediators, e.g. TNF-alpha, may contribute to insulin resistance in hyperglycaemic patients with T2DM and this might be a partial explanation for glucotoxicity.