NORMAL PHYSIOLOGY AND PHENOTYPIC CHARACTERIZATION OF BETA-CELL FUNCTION IN SUBJECTS AT RISK FOR NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Major genes for NIDDM appear to be rare. Therefore, phenotypic charact erization of the pathophysiological changes contributing to hyperglyca emia are assuming increasing importance. Assessment of beta-cell funct ion has been hampered by two major confounding factors during function al testing: variable insulin sensitivity and plasma glucose levels. Th ese and other methodological variables are discussed with recommendati ons for ameliorating or accounting for their impact. A group of tests as used by the Seattle Group for phenotypic characterization is descri bed including basal immunoreactive insulin (IRI), proinsulin, and proi nsulin intermediates (PI); the acute insulin response to glucose (AIR( g)); maximal (AIR(max)), and half-maximal (PG(50)) capacity to potenti ate a non-glucose secretagogue; and insulin-sensitivity (S-1). Specifi c examples in the use of this battery of tests are given. It is conclu ded that such phenotyping will be an important tool for studies of the epidemiology and genetics of NIDDM.