Relationship between bone and adipose tissue in glucose intolerated patients

Osteocalcin, a marker of bone formation, is synthesized in osteoblasts. Animal studies have demonstrated its role as promoting the proliferation of β cells, insulin secretion, and insulin sensitivity. Osteocalcin appears to be associated with glucose homeostasis creating a link between energy metabolism and bone. According to the carboxylation level, osteocalcin can be divided into two groups; one is called uncarboxylated (undercarboxylated) osteocalcin and the other is carboxylated osteocalcin. The uncarboxylated form is the active form of osteocalcin, as a hormone, which has little affinity to bone so that most of it will circulate with the blood, while most of carboxylated osteocalcin will be stored in the bone because of its strong affinity to hydroxyapatite. Besides other factors, osteocalcin synthesis is affected by leptin and adiponectin secretion from the adipose tissue. In the current study, we aimed to investigate circulating levels of osteocalcin in subjects with different glucose tolerance with respect to insulin sensitivity and adipokines. Seventy five subjects (58 women and 17 men; age range 30-65 years) were included in this study. All subjects were recruited from the Endocrinology outpatient unit of the hospital. Weight was measured to the nearest 0.5 kg using a balance beam scale and 333height was measured to the nearest 0.1 cm with a manual height board. The calculated Body Mass Index (BMI; kg/m2) was used as an index of relative weight. After an overnight fasting, 75 g oral glucose tolerance test (75 g-OGTT) was performed and venous blood samples were drawn to determine osteocalcin (intact and uncarboxylated), glucose, insulin, adiponektin and leptin concentrations. Carboxylated osteocalcin levels were calculated. Insulin sensitivity was estimated by Homeostasis model assessment (HOMA) model. According to their OGTT results patients were defined as normal glucose tolerant ( n = 25), prediabetic (n = 25) that included impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and diabetic (n = 25). The study was approved by the Scientific Ethics Committee of Ege University, Medical School. An informed written consent was obtained from all patients. In the first step, subjects were divided into tertiles by uncarboxylated and intact osteocalcin concentrations. Subjects in the upper tertile of uncarboxylated osteocalcin showed higher frequency of normal tolerance and lower tertile of uncarboxylated osteocalcin showed higher frequency of diabetes but it did not reach a statistical significance. The upper intact osteocalcin tertile was associated with higher frequency of normal glucose tolerance. In the second step, subjects were divided according to their OGTT values. In the prediabetic group, carboxylated osteocalcin values were significantly lower than than the normal tolerant and diabetic groups. Finally, patients were grouped using HOMA index ≥ 2.7 as a cut-off for insulin resistance. Serum leptin levels were significantly higher, whereas adiponektin levels were significantly lower in the insulin resistant group. In summary, our data suggest lower carboxylated osteocalsin concentrations are related to glucose homeostasis. Further prospective studies are needed to clarify the mechanism of action of various osteocalcin forms in human glucose homeostasis and insulin resistance.