Partial recovery of insulin secretion and action after combined insulin-sulfonylurea treatment in type 2 (non-insulin-dependent) diabetic patients with secondary failure to oral agents.
Metabolic control, insulin secretion and insulin action were evaluated in seven Type 2 (non-insulin-dependent) diabetic patients with secondary failure to oral antidiabetic agents before and after two months of combined therapy with supper-time insulin (Ultratard: 0.4 U/kg body weight/day) plus premeal glibenclamide (15 mg/day). Metabolic control was assessed by 24 h plasma glucose, NEFA, and substrate (lactate, alanine, glycerol, ketone bodies) profile. Insulin secretion was evaluated by glucagon stimulation of C-peptide secretion, hyperglycaemic clamp (+ 7 mmol/l) and 24 h free-insulin and C-peptide profiles. The repeat studies, after two months of combined therapy, were performed at least 72 h after supper-time insulin withdrawal. Combining insulin and sulfonylurea agents resulted in a reduction in fasting plasma glucose (12.9 +/- 7 vs 10.4 +/- 1.2 mmol/l; p less than 0.05) and hepatic glucose production (13.9 +/- 1.1 vs 11.1 +/- 1.1 mumol.kg-1.min-1; p less than 0.05). Mean 24 h plasma glucose was also lower (13.7 +/- 1.2 vs 11.1 +/- 1.4 mmol/l; p less than 0.05). Decrements in fasting plasma glucose and mean 24 h profile were correlated (r = 0.90; p less than 0.01). HbA1c also improved (11.8 +/- 0.8 vs 8.9 +/- 0.5%; p less than 0.05). Twenty-four hour profile for NEFA, glycerol, and ketone bodies was lower after treatment, while no difference occurred in the blood lactate and alanine profile. Insulin secretion in response to glucagon (C-peptide = +0.53 +/- 0.07 vs +0.43 +/- 0.07 pmol/ml) and hyperglycaemia (freeinsulin = 13.1 +/- 2.0 vs 12.3 +/- 2.2 mU/l) did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
Del Prato
S
S
Cattedra di Malattie del Ricambio, University of Padova, Italy.
Vigili de Kreutzenberg
S
S
Riccio
A
A
Maifreni
L
L
Duner
E
E
Lisato
G
G
Iavicoli
M
M
Tiengo
A
A
D000284:Administration, Oral; D002096:C-Peptide / Q000097:blood; D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D005905:Glyburide / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007267:Injections; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use*; D000078790:Insulin Secretion; D049528:Insulin, Long-Acting; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use*
D002096:C-Peptide; D003692:Delayed-Action Preparations; D007328:Insulin; D049528:Insulin, Long-Acting; C023501:Insulin, Ultratard; D013453:Sulfonylurea Compounds; D005947:Glucose; D005905:Glyburide