Adipocytokines and incident diabetes mellitus in older adults: the independent effect of plasminogen activator inhibitor 1.
BACKGROUND
Adipose tissue produces "adipocytokines" of uncertain clinical significance.


METHODS
We analyzed the relationships among adiposity, adipocytokines, glycemia, and incident diabetes mellitus in 2356 white and black adults aged 70 to 79 years in the Health, Aging, and Body Composition Study who did not have diabetes at baseline. We measured the levels of adipocytokines adiponectin, leptin, interleukin 6, tumor necrosis factor alpha, and plasminogen activator inhibitor 1. Regional fat area was determined by means of computed tomography. New diabetes was defined as a self-reported diagnosis of diabetes or as a fasting plasma glucose level of 126 mg/dL or greater (>/=7.0 mmol/L) at the second, fourth, or sixth annual examination.


RESULTS
A total of 143 participants (14.1 cases per 1000 person-years) developed diabetes across 5 years. Visceral fat area (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.10-1.60 per standard deviation increase) and body mass index (white individuals: OR, 1.65; 95% CI, 1.26-2.15 per standard deviation increase; black individuals: OR, 1.22; 95% CI, 0.99-1.51 per standard deviation increase) independently predicted incident diabetes. Adiponectin, leptin, and plasminogen activator inhibitor 1 attenuated the relationship between adiposity and diabetes. After controlling for body mass index, visceral fat, fasting glucose, fasting insulin, high-density lipoprotein cholesterol, triglycerides, and hypertension at baseline, plasminogen activator inhibitor 1 was the only adipocytokine independently associated with increased odds of diabetes (OR, 1.35; 95% CI, 1.01-1.81). Fasting glucose level at baseline remained a strong predictor of incident diabetes, whereas associations with body mass index and visceral fat were attenuated.


CONCLUSIONS
Adipocytokines and glycemia partially account for the relationship between adiposity and risk of type 2 diabetes due to adiposity. Plasminogen activator inhibitor 1 may be a useful predictor of diabetes in addition to measurements of body fat.
Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, Suite 500, San Francisco, CA 94143-1732, USA. Alka.Kanaya@ucsf.edu
Alka M
AM
Kanaya
Christina
C
Wassel Fyr
Eric
E
Vittinghoff
Tamara B
TB
Harris
Seok Won
SW
Park
Bret H
BH
Goodpaster
Fran
F
Tylavsky
Steven R
SR
Cummings
D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity; D000367:Age Factors; D000368:Aged; D044383:Black People; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000378:metabolism*; D005215:Fasting; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008297:Male; D015999:Multivariate Analysis; D010414:Pennsylvania / Q000453:epidemiology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D013714:Tennessee / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D044465:White People; D001741:Black or African American
D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha