Effect of acute reduction of free fatty acids by acipimox on growth hormone-releasing hormone-induced GH secretion in type 1 diabetic patients.
BACKGROUND
In type 1 diabetes mellitus (DM1), high GH basal levels and exaggerated responses to several stimuli have been described. Acipimox is an antilipolytic drug that produces an acute reduction of free fatty acids (FFA). The aim of this study was to evaluate the effect of the reduction of plasma FFA with acipimox, alone or in combination with GHRH, on GH secretion in DM1.


METHODS
Six type 1 diabetic patients were studied (three women, three men), mean age of 30 +/- 2.1 years, body mass index (BMI) 23.1 +/- 1.5 kg/m2. As a control group, six normal healthy subjects of similar age, sex and weight were studied. Each patient and control received GHRH [1 microg/kg intravenously (i.v.) at min 180], acipimox (250 mg orally at min 0 and 120) and GHRH plus acipimox on three separated days. Subjects served as their own control. Blood samples were taken at appropriate intervals for determination of GH, FFA and glucose.


RESULTS
In control subjects, the GH area under the curve (AUC; microg/l x 120 min) was for acipimox-treated 1339 +/- 292 and 1528 +/- 330 for GHRH-induced secretion. The GH AUC after the administration of GHRH plus acipimox was 3031 +/- 669, significantly greater than the response after acipimox alone (P<0.05) or GHRH alone (P<0.05). In diabetic patients, the GH AUC was for acipimox-treated 2516 +/- 606 and 1821 +/- 311 for GHRH-induced secretion. The GH AUC after the administration of GHRH plus acipimox was 7311 +/- 1154, significantly greater than the response after acipimox alone (P<0.05) or GHRH alone (P<0.05). The GH response after acipimox was increased in diabetic when compared with normal (P<0.05), with a GH AUC of 1339 +/- 292 and 2515 +/- 606 for normal subjects and diabetic patients, respectively. The GH response after acipimox plus GHRH was increased in diabetic when compared with normal (P<0.05), with a GH AUC of 3031 +/- 669 and 7311 +/- 1154 for normal subjects and diabetic patients, respectively. The administration of acipimox induced a FFA reduction during the entire test.


CONCLUSIONS
Reduction of free fatty acids with acipimox is a stimulus for GH secretion in DM1. The combined administration of GHRH plus acipimox induces a markedly increased GH secretion in type 1 diabetic patients when compared with normal subjects. These data suggest that patients with DM1 exhibit a greater GH secretory capacity than control subjects, despite the fact that endogenous FFA levels seems to exert a greater inhibitory effect on GH secretion in these patients.
D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004359:Drug Therapy, Combination; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D011719:Pyrazines / Q000627:therapeutic use*; D013002:Somatomedins / Q000032:analysis
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D011719:Pyrazines; D013002:Somatomedins; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C027696:acipimox