High dose intravenous, but not low dose subcutaneous, insulin-like growth factor-I therapy induces sustained insulin sensitivity in severely resistant type I diabetes mellitus.
We have previously demonstrated weekly iv insulin-like growth factor-I (IGF-I; 500 micrograms/kg) bolus therapy to be effective in inducing sustained insulin sensitivity in a patient with type I diabetes mellitus and massive insulin resistance. The present study was undertaken to determine the efficacy of daily sc IGF-I in the treatment of two severely insulin-resistant type I diabetic patients (requiring in excess of 3500 U insulin/day) compared to weekly iv IGF-I therapy. Prolonged insulin sensitivity was achieved in both patients after weekly 500 micrograms/kg iv bolus infusions of IGF-I, with sc insulin requirements falling to approximately 1 U/kg.day. Smaller iv doses (250 micrograms/kg) of IGF-I were ineffective in acutely lowering serum glucose or inducing sustained insulin sensitivity. However, even this smaller IGF-I dose resulted in acute symptomatic hypophosphatemia, which could be prevented by coadministration of potassium phosphate. With sc administered IGF-I (up to 10 mg twice daily), insulin appeared to control patient glucose concentrations, but severe insulin resistance returned within 72 h of discontinuing IGF-I therapy. IGF-I dosing was decreased to the lowest concentration that maintained euglycemia (7.5 mg in the morning and 2.5 mg in the evening). However, severe arthropathy in both patients and neurological symptoms including multiple cranial nerve palsies in one patient were associated with chronic therapy. We conclude that both iv and sc administered IGF-I can precipitate acute symptomatic hypophosphatemia. Chronic low dose sc therapy may be associated with severe neuropathy and arthropathy, and does not induce the sustained insulin sensitivity associated with high dose intermittent bolus IGF-I therapy.
Usala
A L
AL
Department of Pediatrics, East Carolina University School of Medicine, Greenville, North Carolina 27858.
Madigan
T
T
Burguera
B
B
Cefalu
W
W
Sinha
M K
MK
Powell
J G
JG
Usala
S J
SJ
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D009202:Cardiomyopathies / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D017674:Hypophosphatemia / Q000139:chemically induced; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D007592:Joint Diseases / Q000139:chemically induced; D009422:Nervous System Diseases / Q000139:chemically induced
D001786:Blood Glucose; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D005947:Glucose