PROINSULIN AS A MARKER FOR THE DEVELOPMENT OF NIDDM IN JAPANESE-AMERICAN MEN

Disproportionate hyperproinsulinemia is one manifestation of the B-cel l dysfunction observed in non-insulin-dependent diabetes mellitus (NID DM), but it is unclear when this abnormality develops and whether it p redicts the development of NHDDM. At baseline, measurements of proinsu lin (PI) and immunoreactive insulin (IRI) levels were made in 87 secon d-generation Japanese-American men, a population at high risk for the subsequent development of NIDDM, and, by using World Health Organizati on criteria, subjects were categorized as having normal glucose tolera nce (NGT; n = 49) or impaired glucose tolerance (IGT; n = 38). After a B-year follow-up period, they were recategorized as NGT, IGT, or NIDD M using the same criteria. After 5 years, 16 subjects had developed NI DDM, while 71 had NGT or IGT. Individuals who developed NIDDM were mor e obese at baseline, measured as intra-abdominal fat (IAF) area on com puted tomography (P = 0.046) but did not differ in age horn those who continued to have NGT or IGT. At baseline, subjects who subsequently d eveloped NIDDM had higher fasting glucose (P = 0.0042), 2-h glucose (P = 0.0002), fasting C-peptide (P = 0.0011), and fasting PI levels (P = 0.0033) and disproportionate hyperproinsulinemia (P = 0.056) than tho se who continued to have NGT or IGT after 5 years of follow-np. NIDDM incidence was positively correlated with the absolute fasting PI level (relative odds = 2.35; P = 0.0025), even after adjustment for fasting IRI, IAF, and body mass index (relative odds = 2.17; P = 0.013). Beca use 12 of the 16 subjects who developed NIDDM had IGT at baseline, the 38 IGT subjects were also examined separately. In this cohort, the sa me risk factors (fasting and 2-h glucose, fasting C-peptide, and fasti ng PI levels) were predict;ive for the development of NIDDM. We conclu de that Japanese-American men who subsequently develop NIDDM have more IAF and increased glucose, C-peptide, and PI levels. These data sugge st that alterations in PI may be a new marker for the subsequent devel opment of NIDDM.