| Background The discussion of the potential risk factors for diabetes has been a hotspot in research of endocrine disease, one of which is the special study of adipose cytokines, including adiponectin (APN), resistin, and visfatin. Osteocalcin (OC), as a kind of bone tissue hormone secretion thought to be closely related to osteoporosis, was found similar to adipocytokins in the glucolipid metabolism and played a role in the occurrence and development of obesity. Atherosclerosis disease can exist alone or in combination with diabetes, obesity. OC, as a new endocrine hormone, also has been gradually realized by people and has a certain relationship with atherosclerosis. But no large-scale clinical trials have been made in China.Obejective In this study, we determinate the fasting serum OC levels in the middle age and older males with type 2 diabetes mellitus (T2DM), impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). We investigate the serum OC state at different levels of impaired glucose tolerance and the relevance between the OC and the metabolic indicators, evaluating the correlation between OC and the glycemic variability, discussing the possible role of OC in diabetic macroangiopathy. This study may provide a theoretical basis for the development of OC and its analogues and clinical application in the future.Methods Study 1:All subjects received 75-g oral glucose tolerance test (OGTT), and were divided into three groups, normal glucose tolerance group (group NGT, n=30), impaired glucose tolerance group (group IGT, n=20) and group type 2 diabetes mellitus (T2DM, n=30) according to the diagnostic criteria published by World Health Organization (WHO) in 1999. The T2DM patients were newly diagnosed. All subjects were selected from general outpatient clinic, cadres, healthy control subjects and volunteers in our hospital, collecting metabolism indexes. Serum total OC and APN were assayed using a quantitative enzyme immunoassay (ELISA) kit by laboratory of the SengXiong company in Shanghai. Serum insulin levels were assayed using the method of radioimmunoassay (RIA). Plasma fasting and 2-hour post-challenge glucose levels were assayed using glucose oxidase method. Blood lipid levels were measured by enzymatic method. Homeostatic model assessment Basal insulin secretion and insulin sensitivity were estimated by the homeostaticmodel assessment (HOMA) of pancreatic bate-cell function (HOMA-P) and insulin resistance (HOMA-IR). HOMA-IR=Fins×FPG/22.5. HOMA-p=20xFins/(FPG-3.5). The difference of the metabolic indexes, the relationship among the OC, APN and the metabolism were analyzed. Data were analysed using SPSS for Windows version 13.0. Study 2:Thirty T2DM males with glycosylated haemoglobin (HbAlc) levels between 6.5% nd 9.0% were recruited to the present study. Biochemical information and CGM parameters were collected at baseline and after 8 weeks of antihyperglycaemic therapy (either sulphonylurea, sulphonylurea+an a-glucosidaseinhibitor or insulin+metformin combination therapy). The aim of the present study was to examine the relationship between serum osteocalcin and glycaemic variability, as determined by CGM system in patients with T2DM. Data were analysed using SPSS for Windows version 13.0. Study 3:Like study 1,64 male subjects were collected with clinical datas. The ultrasonographic assessments of the carotid arteries were performed on the participants by an experienced radiologist who was blinded to participants’ etails using a B-mode color Doppler ultrasound with a frequency of 7.5 to 10 MHz (PHILIPS, IU22, USA). Both sides of the carotid artery intima-media thickness(CIMT) were measured three times at the far wall of the distal common carotid arteries, about I cm from the carotid bifurcation. The average values of bilateral arteries were obtained. The aim of the present study was to to investigate the relationship between OC and the severity of CIMT. Data were analysed using SPSS for Windows version 13.0.Result Study 1 (1) Clinical characteristics of subjects such as body mass index (BMI), waist hip ratio (WHR), FPG,2-hour post-challenge glucose(2hPG), systolic blood pressure (SBP), fasting insulin (Fins), total, cholesterol(TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) in three groups were significantly different. (2) There are significant differences in HOMA-IR and HOMA-P among three groups (P<0.01). From NGT to T2DM group, HOMA-IR increases gradually, but HOMA-β reduced gradually. (3) The OC value were obviously decreased in three groups (11.55±0.52μ g/L;6.17±0.36μ g/L;4.85±0.53μg/L)(P<0.01). APN values were obviously decreased (22.76±8.51mg/L;17.44±11.96mg/L;10.06±5.83mg/L)(P<0.01). (4) According to BMI>25kg/m2 and BMI<25/m2, three groups were divided into obese subgroup and non-obese subgroup. Compared with the non-obese subgroup, OC in obese subgroup were lower than non-obese group (P<0.01). (5) In IGT and T2DM groups, the correlation analysis showed that OC, BMI, WHR, FPG,2hPG, HOMA-IR, TG and TC were negatively related. OC values were related positively with HOMA-P and APN. (6) WHR,2hPG, HOMA-IR were independently associated with OC and TG in IGT and T2DM groups. Study 2 (1) Compared with baseline, serum osteocalcin increased significantly CP=0.02), whereas parameters related to glucose variability, including the mean amplitude of glycaemic excursions(MAGE) and the standard deviation of blood glucose values(SDBG), decreased significantly (?<0.01) after the 8 week treatment period. (2) At baseline, there was a positive correlation between serum osteocalcin levels and homeostatic model assessment of bate-cell function (P=0.043), fasting C-peptide levels (FCP)(P=0.001), but a negative correlation between serum osteocalcin levels and fasting plasma glucose(FPG) (P=0.041), HbAlc (P= 0.036), and 24h mean blood glucose(MBG) (P<0.001). (3) Multiple stepwise regression analysis indicated that baseline osteocalcin was the single parameter that best predicted the change in MAGE (β=-0.187, P=0.042). Study 3 (1) Clinical characteristics of subjects such as BMI, WHR, FPG,2hPG, SBP, DBP, Fins, TG, LDL-C, CRP were significantly different in three groups. (2) Compared with NGT group, the serum OC levels were significantly lower in IGT and T2DM groups (10.95±0.04μg/L;6.23±0.45 μg/L;5.13±0.31μg/L) (P<0.01); and OC in T2DM group decreased significantly than that in IGT group (P<0.05). CIMT in the T2DM group were higher than that in IGT and NGT groups (1.108±0.167mm; 1.021±0.119 mm; 1.012±0.141mm) (P<0.05), but in IGT and NGT group, there was no significant difference. (3) The correlation analysis showed that, in the hyperglycemia groups, OC was negatively correlated with BMI, Fins, HOMA-IR,2hPG, HbAlc, TG, CRP and CIMT. OC had positive correlation with APN. CIMT was positively correlated with BMI, HOMA-IR,2hPG, TG and CRP, negatively correlated with APN. (4) Multiple stepwise regression analysis indicated that in hyperglycemia groups, WHR, HOMA-IR,2hPG and HbA1c were independently associated with OC. In T2DM group,2PG, OC, and TG were associated independently with CIMT.Conclusion OC may be involved in insulin resistance, and is closely related to glucose and lipid metabolism. In the males with T2DM, serum osteocalcin concentrations increased with improved glucose control. High initial osteocalcin levels were associated with subsequent improvements in glucose variability during glucose-lowering treatment. In the middle age and older malesmales with T2DM, the change of the CIMT is closely related to the level of OC, high OC level may be a protective factor for atherosclerosis. |
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