Intensification of therapy and no increase in body mass index with longer disease duration in type 2 diabetes mellitus (ZODIAC-5)

Background. Decreased insulin sensitivity and beta-cell failure are the two key components in the pathogenesis of type 2 diabetes mellitus (T2DM). Secondary treatment failure is often attributed to the development of obesity-related insulin resistance in combination with continued loss of beta-cell function.

Objective. Assess metabolic control, body mass index (BMI) and treatment in relationship to diabetes duration to study these mechanisms.

Methods. Cross-sectional study of 7875 patients with T2DM in primary care in The Netherlands. Clinical data and laboratory results were obtained for the 2005 annual visit. Patients were grouped according to diabetes duration in 2-year intervals. Each step in the traditional treatment sequence was considered as a sign of progression of beta-cell failure.

Results. Complete data regarding duration and treatment were available for 6850 patients (87%). After the initial years following diagnosis, treatment with diet alone decreases and oral hypoglycaemic agents (OHA) are prescribed to an increasing percentage of patients. Treatment with OHA diminishes after approximately 10 years following diagnosis and treatment with insulin increases until approximately two-thirds of patients with diabetes duration of more than 20 years are being treated with insulin. BMI does not increase with longer disease duration.

Conclusion. The concept of beta-cell failure as the primary determinant of the chronic progression of T2DM is supported by these results, whereas a deterioration of obesity-related insulin sensitivity as indicator is not supported.