Vitamin D status connect insulin resistance and bone turnover in Chinese non-osteoporosis patients with type 2 diabetes
J. Zhang1,2, J. Ye1, Y. Xue2, Z. Lan1, X. Rao1, Y. Sun1, X. Li3, Z. Zheng2, W. Luo1
1Xiamen Second Hospital affiliated Xiamen Medical College, Xiamen, China
2Department of Endocrinology & Metabolism- Nanfang Hospital affiliated Southern Medical University, Guangzhou, China
3Department of Endocrinology- the Second Hospital of Shanxi Medical University, Taiyuan, China 

Background
Vitamin D status was found closely related to blood glucose and bone metabolism in patients with type 2 diabetes (T2DM)[1-4]. Insufficiency and deficiency of vitamin D is related to development of type 2 diabetes[5]. Vitamin D affected bone metabolism and bone density and resulted in osteopenia and osteoporosis. Insulin resistance raises the risk of osteoporosis [6] .Patients with type 2 diabetes have higher morbidity of vitamin D deficiency, osteopenia, osteoporosis, than that without type 2 diabetes[7]. Currently, concentrations of serum 25-hydroxyvitamin D [25(OH)D] is considered to be an evaluation index of the vitamin D status. Based on the negative relationship between 25(OH)D concentrations and insulin resistance found our research before[8], we boldly hypothesise that vitamin D status connects insulin resistance and bone turnover in non-osteoporosis patients with T2DM. Information is limited about the association between vitamin D status, insulin resistance and bone turnover in Chinese non-osteoporosis patients with T2DM. To our best knowledge, this is the first study explored the relationship between vitamin D status, insulin resistance and bone turnover in Chinese non-osteoporosis patients with T2DM.

Aim
This study explored the relationship between serum 25(OH)D concentrations , bone turnover and insulin resistance in Chinese non-osteoporosis T2DM patients.

Method
This trial included 109 non-osteoporosis patients with T2DM. The parameters below were collected: fasting blood glucose (FBG), 25(OH)D, fasting blood insulin (FINS), serum creatinine (SCr) , glycosylated hemoglobin (HbA1c), calcium (Ca) , phosphorus (P) , parathyroid hormone (iPTH), insulin-like growth factor-1 (IGF-1), bone alkaline phosphatase (BALP), glomerular filtration rate (eGFR), body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) and calcium-phosphorus product were performed. SPSS 19.0 software was used for statistical analysis. Continuous variables were expressed as the mean ±mean standard deviation (SD). Non-normal distribution variables are expressed as median and interquartile range. Independent-sample T test was used to compare viarables, 25(OH)D, HbA1c，FBG，FINS，HOMA-IR，Ca，P，BALP，iPTH and IGF-1, in male and female subjects. Multiple linear regression analysis was used to examine the associations below: ⑴association beween serum 25 (OH)D concentrations and HOMA-IR, analysed as dependent variable with the other significantly associated variables［25(OH)D, eGFR, BMI, age］ as independent variables, ⑵ association beween serum 25 (OH)D concentration and bone metabolism indece (calcium , phosphorus , BALP and IGF-1), 25 (OH)D analysed as dependent variable with the other significantly associated variables (calcium, phosphorus, BALP, IGF-1, eGFR, BMI, age) as independent variables, ⑶association beween insulin resistance and bone metabolism indece (calcium , phosphorus, BALP and IGF-1), HOMA-IR analysed as dependent variable with the other significantly associated variables (calcium, phosphorus, BALP, IGF-1, eGFR, BMI, age) as independent variables , a p value < 0.05 was considered significant. As this was a retrospective study, and the data were anonymously analysed, informed consent was unnecessary.

Results
The average serum 25(OH)D value was 21.10±10.39ng/mL (52.75 ± 25.98 nmol/L), below the sufficiency cutoff value of 30 ng/mL[9]. FINS, FBG , HbA1c, HOMA-IR, 25(OH)D, P, calcium phosphorus production , BALP, IGF-1 were not significantly different in male and female subjects, but the mean HbA1c was significantly higher in men than that in women. Calcium and iPTH were significantly higher in women than in men. There was a positive correlation between 25(OH)D and IGF-1 (β = 0. 581, p = 0.000), a negative correlation between 25(OH)D and BALP  (β = -0. 182, p = 0.021) adjusted by age, BMI , eGFR. There was a negative correlation between 25(OH)D and HOMA-IR (β = -0.349， p =0.000) adjusted by age, BMI , eGFR. Vitamin D status was a predictor of IGF-1（β = 0.581, p = 0.000)，and BALP（β = -0.182, p = 0.021), as the dependent variable, but not eGFR, BMI, age, as independent variables. HOMA-IR were negatively correlated to IGF-1（β = -0.376, p = 0.000)，and positively correlated to BALP（β = 0.232, p = 0.013)， adjusted by age, eGFR , BMI.

Discussion
We speculate that 25(OH)D concentrations may interact with HOMA-IR to influence insulin resistance, thereby affecting bone tureover and eventually increasing the risk of osteoporosis in T2DM patients. Our findings provided extra evidence for the roles of vitamin D in bone turnover and insulin resistance, and suggested new perspectives into effective strategies for type 2 diabetes without osteoporosis intervention.

Keywords: Vitamin D, insulin resistance, 25(OH)D, HOMA-IR, bone turnover

Acknowledgments
The authors acknowledge all the participants in this study.This work was supported by grants from (1) the project of Natural Science Foundation of Xiamen Medical College (K2015-02) and (2) united key task project of important disease of Xiamen Science and Technology Commission and Xiamen Health and Family Planning Commission (3502Z20149032).

Conflict of interest: No conflict of interest

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