The response to short-term intensive insulin therapy in type 2 diabetes.
OBJECTIVE
Although a short course of intensive insulin therapy (IIT) can improve beta-cell function and glycaemic control in most patients with newly diagnosed type 2 diabetes (T2DM), the impact of this intervention in diabetes of longer duration has not been carefully studied. Thus, we sought to evaluate the effect of short-term IIT in patients with established T2DM.


METHODS
Thirty-four patients, with diabetes of mean 5.9 +/- 6.6 years duration, underwent 4-8 weeks of IIT, with 4-h meal test administered at baseline and at 1 day post-IIT. A positive clinical response was defined as fasting glucose < 7.0 mmol/l off any antidiabetic therapy at the latter test.


RESULTS
A positive response was achieved in 68% (n = 23) of the subjects. At baseline meal test, the responders had lower glucose levels than the non-responders from 120 to 240 min (all timepoints p < or = 0.0008) and higher late incremental area-under-the-C-peptide-curve (AUC(Cpep)), particularly from 60 to 150 min (all p < 0.005). Beta-cell function (ratio of AUC(Cpep) to AUC(gluc) divided by HOMA-IR) was similar between the groups at baseline (median 54.1 vs. 51.3, p = 0.62) but after IIT was significantly higher in the responders (109.3 vs. 57.4, p = 0.009). At baseline, the strongest predictors of the change in beta-cell function were glucose levels between 180 and 240 min (all r = -0.5, p = 0.005) and incremental AUC(Cpep) from 120 to 180 min (all r > or = 0.66, p < or = 0.0001), both reflecting late-phase insulin secretion.


CONCLUSIONS
The clinical response to short-term IIT is variable, consistent with the heterogeneity of T2DM. However, preserved late-phase insulin secretion may identify those patients who can benefit from this intervention with improved beta-cell function.
Retnakaran
R
R
Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada. rretnakaran@mtsinai.on.ca
Yakubovich
N
N
Qi
Y
Y
Opsteen
C
C
Zinman
B
B
D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin