Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial.
BACKGROUND
Early intensive insulin therapy in patients with newly diagnosed type 2 diabetes might improve beta-cell function and result in extended glycaemic remissions. We did a multicentre, randomised trial to compare the effects of transient intensive insulin therapy (continuous subcutaneous insulin infusion [CSII] or multiple daily insulin injections [MDI]) with oral hypoglycaemic agents on beta-cell function and diabetes remission rate.


METHODS
382 patients, aged 25-70 years, were enrolled from nine centres in China between September, 2004, and October, 2006. The patients, with fasting plasma glucose of 7.0-16.7 mmol/L, were randomly assigned to therapy with insulin (CSII or MDI) or oral hypoglycaemic agents for initial rapid correction of hyperglycaemia. Treatment was stopped after normoglycaemia was maintained for 2 weeks. Patients were then followed-up on diet and exercise alone. Intravenous glucose tolerance tests were done and blood glucose, insulin, and proinsulin were measured before and after therapy withdrawal and at 1-year follow-up. Primary endpoint was time of glycaemic remission and remission rate at 1 year after short-term intensive therapy. Analysis was per protocol. This study was registered with ClinicalTrials.gov, number NCT00147836.


RESULTS
More patients achieved target glycaemic control in the insulin groups (97.1% [133 of 137] in CSII and 95.2% [118 of 124] in MDI) in less time (4.0 days [SD 2.5] in CSII and 5.6 days [SD 3.8] in MDI) than those treated with oral hypoglycaemic agents (83.5% [101 of 121] and 9.3 days [SD 5.3]). Remission rates after 1 year were significantly higher in the insulin groups (51.1% in CSII and 44.9% in MDI) than in the oral hypoglycaemic agents group (26.7%; p=0.0012). beta-cell function represented by HOMA B and acute insulin response improved significantly after intensive interventions. The increase in acute insulin response was sustained in the insulin groups but significantly declined in the oral hypoglycaemic agents group at 1 year in all patients in the remission group.


CONCLUSIONS
Early intensive insulin therapy in patients with newly diagnosed type 2 diabetes has favourable outcomes on recovery and maintenance of beta-cell function and protracted glycaemic remission compared with treatment with oral hypoglycaemic agents.
Weng
Jianping
J
Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. wjianp@mail.sysu.edu.cn
Li
Yanbing
Y
Xu
Wen
W
Shi
Lixin
L
Zhang
Qiao
Q
Zhu
Dalong
D
Hu
Yun
Y
Zhou
Zhiguang
Z
Yan
Xiang
X
Tian
Haoming
H
Ran
Xingwu
X
Luo
Zuojie
Z
Xian
Jing
J
Yan
Li
L
Li
Fangping
F
Zeng
Longyi
L
Chen
Yanming
Y
Yang
Liyong
L
Yan
Sunjie
S
Liu
Juan
J
Li
Ming
M
Fu
Zuzhi
Z
Cheng
Hua
H
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012074:Remission Induction
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin