Clinical evidence of thiazolidinedione-induced improvement of pancreatic beta-cell function in patients with type 2 diabetes mellitus.
BACKGROUND
There is growing evidence in animal and in vitro studies showing that thiazolidinediones (TZDs) improve pancreatic beta cell (beta-cell) function. The aim of this study was to evaluate the effect of thiazolidinediones on the beta-cell function of patients with Type 2 diabetes mellitus (T2DM) in clinical practice.


METHODS
This is an observational, nested case-control study. We identified 28 patients (TZD group), with T2DM, who had had a meal-stimulated C-peptide level documented before the addition of troglitazone to a failing double-therapy regimen with metformin (MET) and sulphonylurea (SU). As a control group (CTRL), we identified 26 patients, with T2DM, who also had had a meal-stimulated C-peptide documented before adding MET to a failing SU monotherapy regimen. We then proceeded to prospectively remeasure their meal-stimulated C-peptide levels and compared the changes over time between the two groups.


RESULTS
Both groups were well matched for age, body mass index (BMI), and HgbA1c before and after treatment. The C-peptide in the TZD group increased significantly during therapy (from 3.2 +/- 0.5 to 4.2 +/- 0.5, p = 0.01), whereas it remained unchanged in the CTRL group (from 4.8 +/- 0.6 to 5.0 +/- 0.5, p = 0.74). The C-peptide/glucose ratio also increased significantly in the TZD group (from 1.9 +/- 0.3 to 3.1 +/- 0.3, p = 0.0003) whereas it remained unchanged in the CTRL group (from 3.4 +/- 0.7 to 3.4 +/- 0.3, p = 0.97). Furthermore, the C-peptide/glucose ratio of the TZD group, which was significantly lower at baseline compared with the CTRL group (1.9 +/- 0.3 vs. 3.4 +/- 0.7, p = 0.04), caught up to its level during treatment (3.1 +/- 0.3 vs. 3.4 +/- 0.3, p = 0.48).


CONCLUSIONS
Thiazolidinediones seem to induce recovery of pancreatic beta cell function, independently of the correction of glucose toxicity.
Ovalle
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Department of Medicine, Division of Endocrinology & Metabolism, University of Alabama at Birmingham School of Medicine, Birmingham, AL USA.
Bell
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DS
D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004435:Eating / Q000502:physiology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood*; D007515:Islets of Langerhans / Q000378:metabolism*; D008875:Middle Aged; D019518:Postprandial Period; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones
D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione