Coefficient of β-Cell Failure in Patients with Type 2 Diabetes Treated with Pioglitazone or Acarbose

Abstract

Aim

A new method of assessing the coefficient of failure of pancreatic β-cells from any index of glycaemia has been proposed. This method of analysis has been used to assess data on HbA1c and fasting glucose concentrations from a randomised study comparing pioglitazone with acarbose.

Methods

Patients were treated for 26 weeks with either pioglitazone 45 mg once daily or acarbose 300 mg/day as 3 equal doses. Plasma HbA1c concentration was measured every two months and fasting glucose was measured monthly. The coefficient of failure was determined for each patient from the slope of the least squares regression line over time.

Results

The coefficient of failure from HbA1c was - 2.65 ± 2.13 %/year with pioglitazone and - 1.25 ± 3.11 %/year with acarbose, indicating improved β-cell function in each case. The coefficient of failure was improved to a significantly greater extent with pioglitazone (P < 0.001). Coefficient of failure from fasting blood glucose also showed a greater improvement with pioglitazone (- 53.1 ± 95.0 mg/dl/year) than with acarbose (- 29.9 ± 142.5 mg/dl/year; p = 0.049).

Conclusion

The coefficient of failure showed a significantly greater improvement of β-cell function with pioglitazone than with acarbose during 26 weeks of treatment.

Key words

Beta-cell function - coefficient of failure - pioglitazone - acarbose

References

• 1 Albareda M, Rodriguez-Espinosa J, Murugo M, de Leiva A, Corcoy R. Assessment of insulin sensitivity and beta-cell function from measurements in the fasting state and during an oral glucose tolerance test.  Diabetologia. 2000;  43 1507-1511
• 2 Buchanan T A, Xiang A H, Peters R K, Kjos S L, Marroquin A, Goico J, Ochoa C, Tan S, Berkowitz K, Hodis H N, Azen S P. Preservation of Pancreatic β-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women.  Diabetes. 2002;  51 2796-2803
• 3 Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism.  Endocr Rev. 1999;  20 649-688
• 4 Göke B. on behalf of the German Pioglitazone Study Group . Improved glycaemic control and lipid profile in a randomised study of pioglitazone compared with acarbose in patients with type 2 diabetes mellitus.  Treatments Endocrinol. 2002;  1 329-336
• 5 Holman R R, Cull C A, Turner R C. A randomised double-blind trial of acarbose in type 2 diabetes shows improved glycaemic control over 3 years (UKPDS 44).  Diabetes Care. 1999;  22 960-964
• 6 Otto C, Lehke M, Göke B. Novel insulin sensitizers: pharmacogenomic aspects.  Pharmacogenomics. 2002;  3 1-18
• 7 Ovalle F, Bell D SH. Clinical evidence of thiazolidinedione-induced improvement of pancreatic β-cell function in patients with type 2 diabetes mellitus.  Diabetes Obes Metab. 2002;  4 56-59
• 8 Rosenstock J. Improved insulin sensitivity and beta cell responsivity suggested by HOMA analysis of pioglitazone therapy.  Diabetologia. 2000;  43(Suppl 1) A192
• 9 Turner R C, Cull C A, Frighi V, Holman R R. Glycemic control with diet, sulphonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49).  J Am Med Assoc. 1999;  281 2005-2012
• 10 Group U KPDS. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).  Lancet. 1998 a;  352 837-854
• 11 Group U KPDS. UK Prospective Diabetes Study 26: Sulphonylurea failure in non-insulin dependent diabetic patients over 6 years.  Diabet Med. 1998 b;  15 297-303
• 12 Wallace T M, Matthews D R. The assessment of insulin resistance in man.  Diabet Med. 2002 a;  19 527-534
• 13 Wallace T M, Matthews D R. Coefficient of failure: a methodology for examining longitudinal β-cell function in type 2 diabetes.  Diabet Med. 2002 b;  19 465-469
• 14 Weyer C, Bogardus C, Mott D M, Pratley R E. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus.  J Clin Invest. 1999;  104 787-794