Abstract

BACKGROUND: Debate surrounds the relative importance of impaired beta-cell secretory function versus insulin resistance in type 2 diabetes. We therefore defined insulin secretion and sensitivity in patients with impaired glucose homoeostasis of varying aetiology and duration. METHODS: 126 consecutive patients undergoing an oral glucose tolerance test (OGTT) between 1999 and 2003 were included. Whole-body insulin sensitivity index (ISI) and insulinogenic index derived from the OGTT were determined in 32 healthy controls, 65 type 2 diabetic patients, 15 patients with acromegaly, 10 patients with insulinoma, and 4 patients with HAIRAN syndrome. RESULTS: Median ISI (quartiles Q25-Q75) of healthy controls and of patients with insulinoma were similar (3.5 [2.8-5.6] and 3.2 [1.7-4.2] respectively) but significantly decreased in patients with acromegaly, type 2 diabetes, and HAIRAN syndrome (2.8 [1.8-3.3], 1.9 [1.4-3], and 0.8 [0.6-1.3] respectively). Despite the decrease in ISI, patients with HAIRAN syndrome and acromegaly maintained normal glucose tolerance by adapting insulin secretion as reflected in the insulinogenic index (106.5 [90.4-127.5] and 49 [24.4-89] in HAIRAN and acromegaly respectively, versus 46.9 [27.3-66.7] in controls). In contrast, type 2 diabetic patients failed to adapt and displayed severely hampered insulin secretion (insulinogenic index of 7.6 [3.8-14.7]). Furthermore, the level of the insulinogenic index correlated significantly with duration of diabetes and HbA1c, which was not the case for the ISI. Insulinoma patients had a decreased insulinogenic index (38.7 [32-83.8]), leading to impaired glucose tolerance despite normal ISI. CONCLUSIONS: The data are compatible with the notion that beta-cell function rather than insulin sensitivity determines the evolution of hyperglycaemia.