Insulin supplement in type 2 diabetic patients with secondary failure to oral agents ameliorates hepatic and peripheral insulin sensitivity but not insulin secretion.
In order to investigate the mechanism of amelioration of metabolic abnormalities with supplementary doses of insulin, islet B-cell function and insulin sensitivity were measured in 10 patients with Type 2 diabetes in secondary failure to oral agents. A small dose of ultralente insulin (0.26 +/- 0.07 U kg-ideal-body-weight-1) was added in the morning before breakfast. After 3 months insulin therapy and progressive improvement of metabolic control (HbA1 from 10.5 +/- 0.4 to 9.0 +/- 0.3% at the end of insulin treatment, p less than 0.001), basal C-peptide and incremental area during an oral glucose tolerance test were unchanged. In vivo peripheral insulin sensitivity (euglycaemic clamp with insulin infusion of 40, 160, and 600 mU m-2 min-1, respectively) was significantly improved (glucose requirement: to 4.7 +/- 1.0 from 3.0 +/- 0.6 mg kg-1 min-1, p less than 0.05 at first insulin level; to 10.8 +/- 0.5 from 9.3 +/- 0.7 mg kg-1 min-1, p less than 0.01 at second level; to 13.3 +/- 0.6 from 11.8 +/- 0.8 mg kg-1 min-1, p less than 0.025 at third level). Basal hepatic glucose production was also significantly reduced (from 4.3 +/- 0.4 to 3.3 +/- 0.3 mg kg-1 min-1, p less than 0.05), and residual glucose production further suppressed after insulin supplement (from 1.1 +/- 0.4 to 0.3 +/- 0.2 mg kg-1 min-1 after 120 min at 100 mU l-1 plasma insulin, p less than 0.05). Specific insulin binding to mononuclear leucocytes was unchanged (from 3.1 +/- 0.3 to 3.5 +/- 0.3%, NS).
Pisu
E
E
Istituto di Medicina Interna dell'Università degli Studi di Torino, Italy.
De Benedictis
D
D
Baggiore
C
C
Diana
A
A
Marengo
C
C
Bozzo
C
C
Renzetti
A
A
Pagano
G
G
D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D000078790:Insulin Secretion; D049528:Insulin, Long-Acting; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; C023501:Insulin, Ultratard