Rosiglitazone combined with insulin preserves islet beta cell function in adult-onset latent autoimmune diabetes (LADA).
BACKGROUND
LADA is thought to result from the chronic autoimmune destruction of the insulin-producing pancreatic beta cells. In addition to antidiabetic effects, the newly developed insulin sensitizer-thiazolidinediones have the potential to increase the insulin content of islet cells by downregulating local inflammation and autoimmune response. Therefore, we hypothesized that LADA patients might benefit from thiazolidinediones treatment.


METHODS
LADA patients, with a fasting C-peptide (FCP) of 0.3 nmol/L or more, were enrolled and randomly assigned to receive subcutaneous insulin alone (insulin group, n = 12) or rosiglitazone plus insulin (insulin + RSG group, n = 11) to compare the impacts on islet beta cell function. Plasma glucose, HbA 1c, fasting C-peptide (FCP) and C-peptide after 2 h 75-g glucose load (PCP) were determined every 6 months. GAD-Ab and C-peptide were measured with radioimmune assays. Islet beta cell function was evaluated by PCP and DeltaCP(DeltaCP = PCP-FCP).


RESULTS
All of the 23 patients have been followed up for 6 months, 17 cases for 12 months and 14 for 18 months. (1) During 6 months' follow-up, there were no significant changes for DeltaCP and PCP levels in both groups. (2) PCP and DeltaCP levels in insulin + RSG group patients stayed steady during the 12 months' observation (P = 0.161 for both PCP and DeltaCP), while in the insulin alone group, both FCP (P = 0.021) and PCP (P = 0.028) levels decreased significantly. Furthermore, PCP (P = 0.004) and DeltaCP(P = 0.015) differences between 12th month and baseline were higher in insulin + RSG group than those in the insulin group. (3) When observed up to 18 months, PCP and DeltaCP levels in insulin + RSG group patients still stayed steady, while PCP and DeltaCP levels decreased more in the insulin alone group.


CONCLUSIONS
This pilot study suggests that rosiglitazone combined with insulin may preserve islet beta cell function in LADA patients.
Zhou
Zhiguang
Z
Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, Changsha, China. zhouzg@hotmail.com
Li
Xia
X
Huang
Gan
G
Peng
Jian
J
Yang
Lin
L
Yan
Xiang
X
Wang
Jianping
J
D017668:Age of Onset; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors
D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D002097:C-Reactive Protein