Ac. Moses et al., RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR-I INCREASES INSULIN SENSITIVITY AND IMPROVES GLYCEMIC CONTROL IN TYPE-II DIABETES, Diabetes, 45(1), 1996, pp. 91-100
Citations number
37
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Insulin resistance is a major factor in the pathophysiology of type II
diabetes and a major impediment to successful therapy, The identifica
tion of treatments that specifically target insulin resistance could i
mprove diabetes management significantly. Since IGFs exert insulin-lik
e actions and increase insulin sensitivity when administered at suprap
hysiological doses, we determined the effect of 6 weeks of recombinant
human IGF-I (rhIGF-I) administration on insulin resistance and glycem
ic control in obese insulin-resistant patients with type II diabetes.
A total of 12 patients with type II diabetes were recruited for the st
udy, Subcutaneous administration of rhIGF-I (100 mu g/kg b.i.d.) signi
ficantly lowered blood glucose, Fructosamine declined from 369 to 299
mu mol/l by 3 weeks of administration and then declined further to 271
at the end of 5 weeks. Glycosylated hemoglobin, which was 10.4% pretr
eatment, declined to 8.1% at the end of therapy. Mean 24-h blood gluco
se during a modal day was 14.71 +/- 4.5 mmol/l pretreatment and declin
ed to 9.1 +/- 3.21 mmol/l by the end of treatment, These improvements
in glycemia were associated with a decrease in serum insulin levels, M
ean insulin concentrations declined from 108.0 to 57.0 pmol/l during t
he modal day measurements and from 97.2 to 72.0 pmol/l during the mixe
d-meal tolerance test, Changes in glycemia were accompanied by a marke
d increase in insulin sensitivity, The insulin sensitivity index (S-I)
calculated from a frequently sampled intravenous glucose tolerance te
st (FSIVGTT) after the method of Bergman et al, (Bergman RN, Finegold
DT, Ader M: Assessment of insulin sensitivity in vivo. Endocr Rev 6:45
-86, 1985) increased 3.4-fold. Furthermore, the improvement in glycemi
c control was accompanied by a change in body composition with a 2.1%
loss in body fat as calculated by dual energy x-ray absorptiometry wit
hout change in total body weight. Significant side effects were presen
t in some subjects, although nine subjects were able to complete at le
ast 4.5 weeks of the protocol and six subjects completed the entire 6
weeks, Supraphysiological IGF-I concentrations were maintained through
out the study, increasing from 206 mu g/l in the control period to 849
mu g/l at the end of 6 weeks of rhIGF-I treatment, The increase in IG
F-I levels was accompanied by a significant increase in IGF binding pr
otein-a levels, a slight reduction in IGF binding protein-3 levels, an
d an increase in levels of IGF binding protein-1. In summary, IGF-I si
gnificantly lowered blood glucose as reflected by short-term and long-
term indexes of glycemic control and increased insulin sensitivity. It
remains to be determined whether a dosage can be administered that av
oids significant side effects and still achieves reasonable glycemic c
ontrol.