Effects of insulin administration on beta-cell function in subjects at high risk for type I diabetes mellitus.
The aim of the study was to determine the appropriate dose of subcutaneous insulin to induce "beta-cell rest" without any hypoglycemic risk, as the first stop in the investigation of its potential effect in preventing or delaying clinical diabetes mellitus onset in high-risk subjects. Four subjects at high risk for type I diabetes mellitus (first-degree relatives, islet cell antibodies (ICA)-positive, and with diminished first-phase insulin secretion) were compared with four healthy individuals. After hospitalization, urinary C-peptide excretion (UCP) and 24-hour serum profiles for glucose were measured before and after administration of NPH insulin 0.1, 0.2, and 0.3 U x kg body weight per day subcutaneously in a single dose on 4 consecutive days. After insulin 0.1 U x kg body weight, a significant inhibition of endogenous insulin secretion was observed in high-risk subjects, but not in control subjects. There was no further inhibition when a higher insulin dose (0.2 and 0.3) was administered. A sustained beta-cell rest was obtained after 3, 6, and 12 months of treatment with 0.1 U x kg body weight per day as outpatient therapy in high-risk subjects. With this dose, no subject developed hypoglycemia (plasma glucose <50 mg/dL), whereas this adverse effect was detected after 0.2 and 0.3 U x kg body weight in both groups. In conclusion, our results indicate that administration of NPH insulin 0.1 U x kg bodyweight per day induces beta-cell rest without the undesirable effect of hypoglycemic episodes. This is a preliminary study to investigate the potential beneficial effect of insulin in preventing or delaying type I diabetes mellitus in subjects at high risk for the disease.
Rodríguez-Villar
C
C
Endocrinology Unit, Hospital Clínic, Barcelona, Spain.
Conget
I
I
González-Clemente
J M
JM
Vidal
J
J
Navarro
P
P
Casamitjana
R
R
Gomis
R
R
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007279:Injections, Subcutaneous; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007336:Insulin, Isophane / Q000008:administration & dosage* / Q000009:adverse effects; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology*; D008875:Middle Aged; D011236:Prediabetic State / Q000188:drug therapy / Q000503:physiopathology; D012307:Risk Factors; D012449:Safety; D013997:Time Factors
D007004:Hypoglycemic Agents; D007328:Insulin; D007336:Insulin, Isophane