Background.
Hypercortisolism and
type 2 diabetes (T2D) share clinical characteristics. We examined
pioglitazone's effects on the GH-
IGF-I and HPA axes in men with varying
glucose intolerance. Methods. 10 men with T2D and 10 with IGT received
pioglitazone 30-45 mg for 12 weeks. OGTT with microdialysis in subcutaneous adipose tissue and 1 μg
ACTH-stimulation test were performed before and after.
Glucose,
insulin,
IGF-I, IGFBP1, and interstitial measurements were analyzed during the OGTT.
Insulin sensitivity was estimated using HOMA-IR. Results. HOMA-IR improved in both groups.
IGF-I was initially lower in T2D subjects (P = 0.004) and increased during treatment (-1.4 ± 0.5 to -0.5 ± 0.4 SD; P = 0.007); no change was seen in IGT (0.4 ± 39 SD before and during treatment). Fasting
glycerol decreased in T2D (P = 0.038), indicating reduced lipolysis. Fasting
cortisol decreased in T2D (400 ± 30 to 312 ± 25 nmol/L; P = 0.041) but increased in IGT (402 ± 21 to 461 ± 35 nmol/L; P = 0.044). Peak
cortisol was lower in T2D during treatment (599 ± 32 to 511 ± 43, versus 643 ± 0.3 to 713 ± 37 nmol/L in IGT; P = 0.007). Conclusions.
Pioglitazone improved adipose tissue and liver
insulin sensitivity in both groups. This may explain increased
IGF-I in T2D.
Pioglitazone affected
cortisol levels in both groups but differently, suggesting different mechanisms for improving
insulin sensitivity between T2D and IGT.