title: Disproportionately increased proinsulin levels are associated with the insulin resistance syndrome.
abstract: Recent data suggest that proinsulin may be associated with increased cardiovascular risk factors in both diabetic and nondiabetic subjects. We examined the relation of insulin, proinsulin, and the fasting proinsulin/insulin ratio to a number of metabolic disorders believed to be related to the insulin resistance syndrome (low high density lipoprotein cholesterol and high triglyceride levels, hypertension, and impaired glucose tolerance). Proinsulin was measured by a RIA, and insulin was measured by a Linco RIA that does not cross-react with proinsulin. The increased fasting proinsulin/insulin ratio was significantly associated with hypertension, low high density lipoprotein cholesterol and high triglyceride levels, and impaired glucose tolerance in 423 nondiabetic subjects. The fasting proinsulin/insulin ratio increased significantly with the number of metabolic disorders (zero, 0.060; one, 0.086; two, 0.098; three, 0.177; four, 0.182; P < 0.001). The increased proinsulin/insulin ratio was also associated with a greater number of metabolic disorders in diabetic subjects. Our results show that particularly nondiabetic individuals with the insulin resistance syndrome not only have hyperinsulinemia as a marker of insulin resistance, but also show an increase in proinsulin relative to insulin, which may reflect relative beta-cell failure or malfunction.
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio 78284.
authors.forename: S M
authors.initials: SM
authors.lastname: Haffner
authors.forename: L
authors.initials: L
authors.lastname: Mykkänen
authors.forename: R A
authors.initials: RA
authors.lastname: Valdez
authors.forename: M P
authors.initials: MP
authors.lastname: Stern
authors.forename: D L
authors.initials: DL
authors.lastname: Holloway
authors.forename: A
authors.initials: A
authors.lastname: Monterrosa
authors.forename: R R
authors.initials: RR
authors.lastname: Bowsher
mesh_terms: D000886:Anthropometry; D001823:Body Composition; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006973:Hypertension / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D017058:Mexican Americans; D008875:Middle Aged; D011384:Proinsulin / Q000097:blood*; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D007328:Insulin; D014280:Triglycerides; D011384:Proinsulin