Background and aims: The skeleton is recognized as an important player in energy metabolism and may be linked to glucose metabolism through osteocalcin, a bone-derived protein. Animal studies have shown that osteocalcin may enhance insulin secretion and insulin sensitivity, but in humans data are more ambiguous. Our aim was therefore to investigate the relationship of s-osteocalcin levels with insulin sensitivity and insulin secretion in humans.Methods and subjects: Glucose metabolism related parameters and serum osteocalcin were measured in a multiethnic population of 61 subjects, 42 Nordic and 19 South-Asian, with type 2 diabetes. Mean age was 56.0 + 9.0 years, BMI 31.8 + 5.0 kg/m2 and duration of diabetes 10 + 6 years. Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp, while insulin secretion was measured by intravenous glucose tolerance test (IVGTT).Results: All participants had s-osteocalcin levels within the normal range. Subjects with s-osteocalcin levels less than median had higher BMI and fat percent, more elevated fasting p-glucose and lower insulin sensitivity compared to those above or similar to median. S-osteocalcin levels were inversely correlated with fasting p-glucose. There were no differences in s-osteocalcin concentration between the ethnic subpopulations, but s-osteocalcin levels were positively associated with insulin sensitivity in the South-Asian, but not Nordic subjects.Conclusions: Insulin sensitivity was better and fasting p-glucose lower in subjects with s-osteocalcin levels above or similar to median. S-osteocalcin levels were positively associated with insulin sensitivity in South-Asian subjects only. These findings indicate that s-osteocalcin may modulate with glucose metabolism, and that the effect might be dependent on ethnicity.