WHO and ADA criteria for the diagnosis of diabetes mellitus in relation to body mass index. Insulin sensitivity and secretion in resulting subcategories of glucose tolerance

OBJECTIVE: To determine the influence of body mass index (BMI) on agreement between the American Diabetes Association (ADA) and the new World Health Organization diagnostic criteria for the diagnosis of diabetes mellitus and to investigate the metabolic profile of the resulting subcategories. DESIGN: Cross-sectional study SUBJECTS: A total of 3018 subjects with no previous history of diabetes and fasting glucose < 7.8 mmol/l, with a wide range of BMIs. MEASUREMENTS: (1) Prevalence of impaired glucose regulation (IGR) and diabetes (DM) according to ADA and WHO diagnostic criteria; (2) basal and post-load insulin sensitivity and secretion, calculated on the basis of data derived from an oral glucose tolerance test (OGTT). RESULTS: The diagnosis according to the two classifications was concordant in 2490 subjects, discordant in 528 (452 were identified as impaired glucose tolerance (IGT) and 76 as DM only by means of OGTT). The disagreement increased with increasing BMI, being as high as 25.3% in subjects with BMI ≥ 35 kg/m(2). Subjects with isolated fasting hyperglycaemia were mainly characterised by reduced insulin sensitivity and secretion in the basal state, but normal first-phase insulin secretion and moderately reduced insulin sensitivity after glucose challenge. Subjects with isolated 2 h hyperglycaemia were mainly characterised by normal basal insulin secretion and by a marked insulin resistance associated with a blunted first-phase insulin secretion after the glucose load. CONCLUSIONS: The disagreement between ADA and WHO classifications is particularly relevant in obesity, making OGTT mandatory in these subjects. Different pathogenic mechanisms are involved in isolated fasting or post-load hyperglycaemia, possibly related to a different site of insulin resistance (hepatic vs peripheral), and/or to a different disregulation of insulin secretion (basal vs post-load). A correct identification of the underlying mechanism(s) is the rationale for future studies to detect the effectiveness of different pharmacological or behavioural approaches.