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Newly identified adipokine associated with bone density in type 2 diabetes

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February 13, 2018

Patients with type 2 diabetes and osteopenia or osteoporosis have lower levels of serum retinol-binding protein 4, suggesting the adipokine may play a protective role in maintaining bone mineral density, according to findings from a study in China.

“Retinol-binding protein 4 (RBP4), a newly identified adipokine, secreted by adipocytes and the liver, [functions] as the retinol transporter,” Jin Zhou, of the department of endocrinology at Affiliated Yantai Yuhuangding Hospital of Qingdao University in Shandong, China, and colleagues wrote in the study background. “RBP4 emerged as a critical factor in insulin resistance and obesity. Serum RBP4 levels were found significantly elevated in type 2 diabetes and obese individuals. However, the relationship between serum RBP4 levels and bone metabolic factors, especially diabetes and osteopenia, diabetes and osteoporosis comorbidity individuals, have never been determined.”

Zhou and colleagues analyzed data from 274 Han Chinese patients with type 2 diabetes aged at least 50 years who were hospitalized between May 2016 and February 2017 (165 women; mean age, 63 years; mean diabetes duration, 11.5 years; mean BMI, 26.22 kg/m²). Patients completed questionnaires and provided fasting blood samples to assess plasma alkaline phosphatase (ALP), calcium, phosphorus, magnesium, HbA1c, serum parathyroid hormone (PTH) and RBP4. They also underwent DXA measurements to assess BMD at the lumbar spine, femoral neck and hip. Patients were stratified into three groups based on DXA T-score: normal BMD (n = 148), osteopenia (n = 94) and osteoporosis (n = 33). Researchers used linear regression analysis to model associations between retinol and BMD.

Compared with patients who had type 2 diabetes and normal BMD, researchers observed a bivariate correlation between RBP4, body weight and BMI and BMD at all measured sites in patients with type 2 diabetes and osteopenia or osteoporosis, whereas calcium levels were positively associated with BMD at the lumbar spine and hip. Age and diabetes duration were negatively associated with BMD at both the femoral neck and hip; however, there were no observed associations between those two factors and BMD at the lumbar spine. There were no bivariate associations between HbA1c or PTH with BMD.

RBP4 was strongly associated with serum calcium (r = 0.243; P < .05), body weight (r = 0.153; P < .01) and BMI (r = 0.12; P < .05), according to researchers. In multiple regression analysis, serum RBP4 levels had a graded, stepwise positive association with BMD at all measured sites, which persisted after adjustment for age, body weight, BMI and other bone-related factors.

The researchers noted that the study was limited by the small number of enrolled patients with type 2 diabetes and osteoporosis, and that other adipokines and metabolic bone markers were not included due to limited resources.

“Intriguingly, RBP4 maintained a strong association with BMD after adjustments for other factors that influence BMD,” the researchers wrote. “We speculate that RBP4, in addition to BMI, weight and calcium, have a protective role in bone mass maintenance.” – by Regina Schaffer

Disclosures: The authors report no relevant financial disclosures.