Endocrine Abstracts

Acromegaly causes impaired insulin sensitivity and reduced fat mass. Using acipimox to block lipolysis, the impact of free fatty acids (FFA) on insulin sensitivity in active acromegaly was investigated. ¹H MRS was used to quantify triglyceride (TG) content of liver and muscle.

Methods: 6 patients with active acromegaly (AA) (5M, age 59 (34–70), IGF-I (ng/ml) (median (range)) (452 (342–1002)) were studied on 2 visits; (i) baseline (BL) (ii)after Acipimox (WA) 250 mg 4 hourly 2000–0800 h. Using stable isotopes of glucose allowed insulin sensitivity assessment under basal conditions overnight (ON). Minimal modeling (MINMOD) of a frequently sampled IVGTT provided estimations of insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response to glucose (AIRg) and disposition index (DI).

8AA (6M, age 39.5 (23–66), IGF-I (ng/ml) 541 (326–1244) and 5 healthy volunteers (HV) (3M age 30.5 (28–39)) had liver, gastrocnemius (GN) and tibialis anterior (TA) TG content estimated by ¹H MRS.

Results: Basal: Mean ON insulin (AUC(S.D.) mU h per l) was lower with Acipimox (WA) vs Baseline (BL) (135 (52) vs 279 (97), P=0.04). Mean ON glucose (AUC (±2 S.D.) mmol h per l) was lower WA vs BL (52 (4) vs 63 (9), P=0.03). Hepatic insulin sensitivity (HIS) higher in all WA vs BL (min l/mmol per pmol×10²) (16.3 (8.3) vs 8.4 (3.3), P=0.02).

Stimulated: Si (10⁻⁴ ml/uU per min) was higher WA vs BL in 4 of 5 successful models, (mean(S.D.)) (14.1 (18.2) vs 16.7 (11.9), P=NS); Sg (per min×10³) no difference observed WA vs. BL (11.3 (4.3) vs 12.2 (3.2), n=5, P=NS); AIRg (uU/ml min) improved WA vs BL (66.3 (46.2) vs 40.1 (33.7), n=5, P=0.01). DI (×10³) improved WA vs BL (98.5 (74) vs 45.2 (56.6), n=5, P=0.01).

Liver TG:Water ratio was lower in AA than HV; median(range) (0 (0–0.05) vs 0.12 (0.02–0.22), P=0.01).

Conclusion: These results suggest that lipolysis is a key factor in impaired insulin sensitivity in acromegaly. Inhibiting lipolysis (decreasing FFA production) improves peripheral and hepatic insulin sensitivity, and restores 1st phase insulin secretion. The low hepatic fat observed suggests that FFA flux may be acting as a substrate for increased hepatic glucose production, which is reduced by lipolysis inhibition.