Insulin intervention in slowly progressive insulin-dependent (type 1) diabetes mellitus.

Abstract

OBJECTIVE:

We tested the hypothesis that insulin therapy rather than sulfonylurea (SU) treatment is preferable to reverse or preserve beta-cell function among patients with slowly progressive insulin-dependent (type 1) diabetes (SPIDDM) or latent autoimmune diabetes in adults.

METHODS:

This multicenter, randomized, nonblinded clinical study screened 4089 non-insulin-dependent diabetic patients for glutamic acid decarboxylase autoantibodies (GADAb). Sixty GADAb-positive non-insulin-requiring diabetic patients with a 5-yr duration or shorter of diabetes were assigned to either the SU group (n = 30) or the insulin group (n = 30). Serum C-peptide responses to annual oral glucose tolerance tests were followed up for a mean of 57 months. The primary endpoint was an insulin-dependent state defined by the sum of serum C-peptide values during the oral glucose tolerance test (SigmaC-peptide) less than 4 ng/ml (1.32 nmol/liter).

RESULTS:

The progression rate to an insulin-dependent state in the insulin group (three of 30, 10%) was lower than that in the SU group (13 of 30, 43%; P = 0.003, log-rank). Longitudinal analysis demonstrated that SigmaC-peptide values were better preserved in the insulin group than in the SU group. Multiple regression analysis demonstrated that insulin treatment, a preserved C-peptide response, and a low GADAb titer at entry were independent factors in preventing progression to an insulin-dependent state. Subgroup analysis suggested that insulin intervention was highly effective for SPIDDM patients with high GADAb titers [> or =10 U/ml (180 World Health Organization U/ml)] and preserved beta-cell function [SigmaC-peptide > or = 10 ng/ml (3.31 nmol/liter)] at entry. No severe hypoglycemic episodes occurred during the study.

CONCLUSIONS:

Insulin intervention to preserve beta-cell function is effective and safe for patients with SPIDDM or latent autoimmune diabetes in adults.

• Authors: Taro Maruyama, Shoichiro Tanaka, Akira Shimada, Osamu Funae, Akira Kasuga, Azuma Kanatsuka, Izumi Takei, Satoru Yamada, Norikazu Harii, Hiroki Shimura, Tetsuro Kobayashi
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 93 Issue 6 Pg. 2115-21 (Jun 2008) ISSN: 0021-972X [Print] United States
• PMID: 18397986 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Autoantibodies
• Blood Glucose
• C-Peptide
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Insulin
• Sulfonylurea Compounds
• hemoglobin A1c protein, human
• Glutamate Decarboxylase

Topics

• Adult
• Aged
• Autoantibodies (analysis, blood)
• Blood Glucose (drug effects)
• Body Mass Index
• C-Peptide (metabolism)
• Diabetes Mellitus, Type 1 (blood, drug therapy, immunology, metabolism)
• Disease Progression
• Dose-Response Relationship, Drug
• Female
• Follow-Up Studies
• Glucose Tolerance Test
• Glutamate Decarboxylase (immunology)
• Glycated Hemoglobin (analysis)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Insulin (administration & dosage, therapeutic use)
• Male
• Middle Aged
• Sulfonylurea Compounds (therapeutic use)
• Time Factors