A rapid increase in beta-cell function by multiple insulin injections in type 2 diabetic patients is not further enhanced by prolonging treatment.
OBJECTIVE
Intensive insulin treatment in type 2 diabetes can improve beta-cell function. It is not known which duration of treatment achieves maximal improvement. We addressed this question in type 2 diabetic patients who displayed features of 'secondary failure'.


METHODS
Ten patients were randomized to multiple insulin injection (MI) therapy for 9 weeks. Another 10 patients started with bedtime insulin (BTI) and continued their peroral medication. Following 9 weeks of treatment, patients on MI switched to BTI and glibenclamide.


RESULTS
Three days of MI led to a decrease in fasting proinsulin/insulin ratio, 0.43 +/- 0.20 vs. 0.29 +/- 0.11, P=0.01 and an increase in glucagon-stimulated C-peptide over baseline, 0.77 +/- 0.43 vs. 1.28 +/- 0.44 nmol L-1, P 0.02. Nine weeks of MI treatment successively decreased fasting and nonfasting blood glucose in parallel with increasing insulin dosage. Initial improvements in secretion parameters were upheld but not further enhanced, the 9 week proinsulin/insulin ratio being 99 +/- 23% and that of glucagon-stimulated C-peptide being 95 +/- 24% of the values obtained after 3 days of treatment. Eight weeks after termination of MI there persisted a total weight gain that tended to be larger than after continuous peroral medication with BTI.


CONCLUSIONS
Improvement of insulin secretion by intensive insulin treatment is rapidly gained with no further effect obtained after a longer treatment period. This finding, as well as undesirable effects of MI on body weight, argues against prolonged MI treatment as a prelude to other therapeutic regimens in type 2 diabetic patients.
Kärvestedt
L
L
Stockholm's Sjukhem Foundation, Stockholm, Sweden. lars.karvestedt@stockholmssjuk-hem.se
Andersson
G
G
Efendic
S
S
Grill
V
V
D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005934:Glucagon / Q000378:metabolism; D005905:Glyburide / Q000008:administration & dosage / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D005934:Glucagon; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin