1型和2型糖尿病患者血清硬骨抑素、Dickkopf相关蛋白1、鸢尾素水平比较

Comparison of serum levels of sclerostin,Dickkopf-related protein 1,and irisin in patients with type 1 and type 2 diabetes

目的1型糖尿病与2型糖尿病均有骨代谢异常,但发病机制存在差异。硬骨抑素(sclerostin,SOST)、Dickkopf相关蛋白1(Dickkopf-related protein 1,DKK-1)、鸢尾素是新近发现的骨代谢调节因子。本研究拟比较1型糖尿病与2型糖尿病患者血清SOST、DKK-1、鸢尾素水平的差异。方法本横断面研究纳入2017年至2019年于北京协和医院内分泌科门诊就诊的101例1型糖尿病患者、2014年至2015北京昌平社区2型糖尿病管理项目中经口服葡萄糖耐量试验筛查确诊的55例2型糖尿病患者和59名糖耐量正常受试者。使用酶联免疫吸附测定法测SOST、DKK-1及鸢尾素,并分析其组间差异。结果本研究女性多于男性,平均年龄49岁。1型糖尿病组较2型糖尿病组病程更长(P<0.001),HbA1C更高(P<0.001),两组间年龄差异无统计学意义。1型糖尿病和2型糖尿病组的血清1型原胶原N端前肽(P1NP)均低于对照组[(8579±400)pg/mL,(7268±552)pg/mL对(10051±618)pg/mL,P=0.039,P=0.001],而1型胶原C端肽交联β降解产物(β-CTX)与对照组相比差异无统计学意义。1型糖尿病和2型糖尿病组SOST均高于对照组[(129.7±6.8)pg/mL,(104.8±6.8)pg/mL对(85.9±5.3)pg/mL,P<0.001,P=0.030],1型糖尿病与对照组差异在校正血糖、血脂等因素后失去统计学意义,1型糖尿病组与2型糖尿病组组间SOST差异无统计学意义。1型糖尿病组和2型糖尿病组DKK-1与对照组差异无统计学意义,1型糖尿病组DKK-1较2型糖尿病组更低或倾向于更低。1型糖尿病组鸢尾素高于对照组及2型糖尿病组[(16.6±0.7)ng/mL对(9.6±0.6)ng/mL,(9.8±0.6)ng/mL,均P<0.001],2型糖尿病组鸢尾素与对照组差异无统计学意义。结论1型糖尿病及2型糖尿病患者成骨指标P1NP受到抑制,破骨指标β-CTX无显著改变。SOST在1型糖尿病及2型糖尿病患者中均升高或呈升高趋势,可能与其成骨抑制相关。而1型糖尿病患者还存在鸢尾素升高,也可能参与其骨转换异常的发生发展。

Objective Both type 1 diabetes and type 2 diabetes are associated with abnormal bone metabolism,but they have different pathogenic mechanisms.Sclerostin(SOST),Dickkopf-related protein 1(DKK-1),and irisin are newly discovered factors involved in the regulation of bone metabolism.This study aims to compare the differences in serum levels of SOST,DKK-1,and irisin between patients with type 1 diabetes and type 2 diabetes.Methods This cross-sectional study included 101 patients with type 1 diabetes who visited the Endocrinology Department of Peking Union Medical College Hospital from 2017 to 2019,as well as 55 patients with type 2 diabetes and 59 individuals with normal glucose tolerance who were confirmed through an oral glucose tolerance test as part of the Beijing Changping Community Type 2 Diabetes Management Program from 2014 to 2015.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of SOST,DKK-1,and irisin.Results There were more female participants than male participants,with an average age of 49 years.The group with type 1 diabetes had a longer duration of illness(P<0.001)and higher HbA1C levels(P<0.001)compared to the group with type 2 diabetes,and there was no statistical difference in age between the two groups.Both the type 1 diabetes and type 2 diabetes groups had lower levels of serum procollagen type 1 N-terminal propeptide(P1NP)compared to the control group[(8579±400)pg/mL,(7268±552)pg/mL vs(10051±618)pg/mL,P=0.039,P=0.001];But theβisomer of C-terminal cross-linking telopeptide of type 1 collagen(β-CTX)showed no statistical difference compared to the control group.Patients with type 1 diabetes and type 2 diabetes had higher SOST than controls[(129.7±6.8)pg/mL,(104.8±6.8)pg/mL vs(85.9±5.3)pg/mL,P<0.001,P=0.030],the differences between the type 1 diabetes group and the control group lost statistical significance after adjusting for factors such as fasting blood glucose and lipid levels.There was no significant difference in SOST between type 1 diabetes and type 2 diabetes groups.There was no significant difference in DKK-1 among three groups,but DKK-1 in type 1 diabetes group was lower or tended to be lower than that in type 2 diabetes group.Serum irisin in patients with type 1 diabetes was higher than that in controls and patients with type 2 diabetes[(16.6±0.7)ng/mL vs(9.6±0.6)ng/mL,(9.8±0.6)ng/mL,both P<0.001],but there was no significant difference in irisin level between type 2 diabetes and controls.Conclusions Patients with both type 1 and type 2 diabetes showed inhibition of the bone formation marker P1NP,while the bone resorption markerβ-CTX did not significantly change.SOST levels were elevated or showed an increasing trend in both type 1 and type 2 diabetes patients,which may be related to the inhibition of bone formation.Additionally,type 1 diabetes patients had increased levels of irisin,which may be involved in abnormal bone turnover.