Low plasma insulin-like growth factor-1 levels are associated with reduced insulin sensitivity and increased insulin secretion in nondiabetic subjects.
OBJECTIVE
Weight gain is associated with a decline in insulin sensitivity and a compensatory increase in insulin secretion. IGF-1 is a plausible candidate to explain these divergent phenomena. In this cross-sectional study, we analyzed the relationship between IGF-1 levels, insulin sensitivity and secretion in 110 nondiabetic subjects with a wide range of BMI to verify this hypothesis.


RESULTS
Subjects underwent OGTT, IVGTT and euglycemic-hyperinsulinemic clamp. HOMA-beta, IVGTT-derived and OGTT-derived indexes for first-phase and second-phase insulin secretion were higher in obese as compared with overweight and normal-weight groups, while glucose disposal was lower. IGF-1 levels were negatively correlated with IVGTT-derived and OGTT-derived indexes first-phase and second-phase insulin secretion, and positively correlated with glucose disposal. These correlations were no longer significant after adjustment for BMI. In a multivariate analysis, the variables associated with glucose disposal were IGF-1, age, triglycerides, and 2-h post-load glucose accounting for 23.4% of its variation. When BMI was entered into the model, the variables associated with glucose disposal were triglycerides, 2-h post-load glucose and BMI accounting for 27.2% of variation. In a multivariate analysis, the only variable associated with IVGTT-derived first-phase and second-phase insulin secretion was IGF-1 accounting for 10.4% and 15.1% of variation, respectively. When BMI was entered into the model, it became the only variable associated with both first-phase and second-phase insulin secretion accounting for 25.7% and 37.6% of variation, respectively.


CONCLUSIONS
These data suggest that progressive reduction in IGF-1 levels may be involved in obesity-related changes in both insulin sensitivity and secretion.
Department of Experimental and Clinical Medicine, University Magna-Graecia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy.
E
E
Succurro
F
F
Andreozzi
M A
MA
Marini
R
R
Lauro
M L
ML
Hribal
F
F
Perticone
G
G
Sesti
D050154:Adiposity; D000328:Adult; D000368:Aged; D000375:Aging; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications; D050177:Overweight / Q000097:blood / Q000150:complications; D014280:Triglycerides / Q000097:blood; D044465:White People; D055815:Young Adult
D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I