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).


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.


CONCLUSIONS
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.
Lindmark
S
S
Department of Medicine, Umeå University Hospital, Umeå, Sweden.
Burén
J
J
Eriksson
J W
JW
D000273:Adipose Tissue / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone; D000704:Analysis of Variance; D001786:Blood Glucose / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D003907:Dexamethasone; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005938:Glucocorticoids; D015309:Glucose Clamp Technique; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000378:metabolism*; D016014:Linear Models; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D002097:C-Reactive Protein; D006854:Hydrocortisone