The purpose of this study was to investigate the association between type 2 diabetes mellitus (DM2) and trabecular volumetric bone mineral density (vBMD) of the thoracic and lumbar spine measured by quantitative computed tomography (QCT) in 483 female (410 with DM2) and 398 male (365 with DM2) adults (age 36-86 years, BMI 16-58, 88% with DM2) in the Diabetes Heart Study. After accounting for familial correlation using generalized estimating equations (GEE), lumbar spine vBMD was positively associated with BMI (r = 0.24, P < 0.0001) and inversely associated with age (r = -0.51, P < 0.0001). In women, age-adjusted thoracic spinal vBMD (mg/ml, mean +/- SE) was higher in diabetics (147.6 +/- 2.3) compared to unaffected individuals (138.6 +/- 3.4) (P = 0.02), with age-adjusted lumbar spinal vBMD showing a similar but non-significant trend (132.9 +/- 2.1 in diabetics vs. 127.2 +/- 3.6 in unaffected individuals, P = 0.15). In contrast, in men, age-adjusted lumbar and thoracic vBMD were not different between diabetics and unaffected controls (lumbar vBMD = 125.0 +/- 1.8 in diabetics and 125.8 +/- 5.6 in unaffected individuals, P = 0.89; thoracic vBMD = 137.4 +/- 2.1 in diabetics vs. 134.2 +/- 5.5 in controls, P = 0.56). After multivariate analysis adjusting for age, sex, race, BMI, physical activity, dietary intake, smoking, and alcohol use, interaction between diabetes status and trabecular vBMD of the spine was no longer observed. In women only, age-adjusted areal BMD (determined by dual X-ray absorptiometry (DXA)) of the spine and hip were significantly higher in diabetics than non-diabetic (all P < 0.05), although the differences disappeared after additional adjustment for BMI. These data suggest that areal BMD measured by DXA and trabecular volumetric BMD measured by QCT are not associated with type 2 diabetes independently from BMI.