Fasting affects serum insulin-like growth factors (IGFs) and IGF-binding proteins differently in patients with noninsulin-dependent diabetes mellitus versus healthy nonobese and obese subjects.
In the present study we have 1) assessed how differences in insulin and GH status between obese patients with noninsulin-dependent diabetes mellitus (NIDDM) and healthy obese (OB) and nonobese (NOB) subjects are associated with different responses of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) to fasting, and 2) determined whether the IGF-I response to fasting in healthy subjects is secondary to changes in IGFBP-3. In patients with NIDDM, there was a lack of response of serum IGF-I concentrations to 4 days of fasting, contrasted with the significant decrease in IGF-I concentrations in NOB subjects (37%; P < 0.001) and the delayed and attenuated decrease in OB subjects (23%; P < 0.01). Insulin and the insulin-regulated IGFBP-1 were also unchanged during fasting in NIDDM, whereas insulin was decreased and IGFBP-1 was increased in both NOB and OB subjects. Insulin-resistant NIDDM patients, with high basal glucose and insulin, normal IGFBP-1, and low GH, had decreased prefasting serum IGF-I concentrations, similar to the values in fasted body mass index- and age-matched OB subjects. IGFBP-3, the major determinant of the IGF-I turnover rate in serum, was unchanged by fasting, as determined by RIA and Western ligand blot analysis. In accordance, no induction of IGFBP-3 proteolytic activity by fasting could be demonstrated. Serum IGF-II concentrations were also unchanged by fasting. Basal immunoreactive IGFBP-3 levels did not differ among the groups, whereas IGFBP-3 by Western ligand blot analysis was decreased in NIDDM in accordance with the finding of increased IGFBP-3 proteolysis in NIDDM. In conclusion, 1) differences in GH status and modulation of GH induction of IGF-I by insulin resistance could contribute to low basal IGF-I levels and lack of a IGF-I response to fasting in patients with NIDDM; and 2) the turnover rate of IGF-I in serum, which is largely determined by IGFBP-3, is not likely to be altered by short term fasting, suggesting that the decrease in serum IGF-I concentrations is a result of decreased IGF-I production.
Bang
P
P
Department of Endocrinology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Brismar
K
K
Rosenfeld
R G
RG
Hall
K
K
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology; D002352:Carrier Proteins / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D005215:Fasting / Q000502:physiology*; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000503:physiopathology; D011863:Radioimmunoassay
D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone