Because a series of reports suggests the existence of altered bone and mineral metabolism in diabetes mellitus, we studied 106 diabetic subjects (42 insulin-dependent (IDD) and 64 noninsulin dependent (NIDD] to determine whether a difference in bone turnover (evaluated by serum osteocalcin (OC] could be found in comparison with normal controls. OC levels in diabetic subjects were lower than the age- and sex-specific predicted values. The reduction was especially evident in male and female NIDD (Z-score: - 1.12 +/- 0.92, t = 8.4, P less than 0.001 and -0.84 +/- 0.86, t = 4.0, P less than 0.01, respectively) and male IDD (Z-score: - 0.90 +/- 0.86, t = 4.5, P less than 0.01). The mean Z-score for female IDD, albeit negative (-0.31 +/- 0.79; t = 1.6; 0.2 greater than P greater than 0.1), was not significantly different from normal. Total serum calcium (Ca) and calcitonin (CT) showed an opposite pattern, being higher in all the diabetic subgroups (with the exception of Ca in female IDD), whereas parathyroid hormone (PTH) was lower than expected in each diabetic subset. By multiple regression analysis, the reduction of OC was related to PTH and CT levels and to the type of treatment. Subjects controlled with diet showed differences of greater magnitude from the expected normal values than those treated with oral hypoglycemic agents or insulin (Z-score: -1.28 +/- 1.05 vs. -0.85 +/- 0.90 and -0.63 +/- 0.97, respectively; P = 0.05). However, the variance explained by these three factors was small, suggesting that other variables (possibly 1 alpha,25(OH)2D) exerted important influences on OC levels.