兰州大学机构库 >第一临床医学院
2型糖尿病C肽水平与骨密度、骨折风险相关性研究
Alternative TitleCorrelation between C-peptide and bone mineral density and fracture risk in patients with type 2 diabetes mellitus
杨虹
Subtype硕士
Thesis Advisor吕海宏
2023-05-31
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name医学硕士
Degree Discipline内科学
Keyword2型糖尿病 Type 2 diabetes mellitus C肽 C-peptide 骨密度 bone mineral density 骨折风险 fracture risk
Abstract

目的

既往研究认为C肽无生物学活性,然而近期研究显示C肽对糖尿病并发症及骨代谢有一定影响。因此本研究对2型糖尿病(Type 2 diabetes mellitus,T2DM)患者C肽水平与骨密度(Bone mineral density,BMD)、骨折风险之间的关系进行探究,进而揭示C肽对糖尿病性骨质疏松及骨折风险的临床预测价值。

方法                      

纳入兰州大学第一医院T2DM患者540例,按空腹C肽(Fasting C-peptide ,FCP)水平三分位间距分为三组:FCP≤1.14ng/ml组,1.14<FCP≤1.73 ng/ml组和FCP>1.73ng/ml组。收集临床资料,包括:性别、年龄、T2DM病程、T2DM并发症、吸烟史、饮酒史、用药情况、父母髋部骨折史和既往病史、体重指数(Body mass index,BMI)。

应用电化学发光免疫分析法测定甲状旁腺激素(Parathyroid hormone,PTH)、25羟维生素D [25 hydroxy vitamin D,25(OH)D]、Ⅰ型原胶原N-端前肽(Procollagen type Ⅰ N-propeptide,PⅠNP)和Ⅰ型胶原C-末端肽β特殊序列(βisomer of C-terminal telopeptide of type Ⅰ collagen,β-CTX),应用化学发光法测定空腹胰岛素(Fasting insulin,FIns)和FCP,应用高压液相色谱法测定糖化血红蛋白(Glycosylated hemoglobin,HbA1c)。应用葡萄糖氧化酶法测定空腹血浆葡萄糖(Fasting plasma glucose,FPG),应用肌氨酸氧化酶法测定肌酐(Creatinine,Cr),应用CHOD-PAP法测定总胆固醇(Total cholesterol,TC),应用GPO-PAP法测定甘油三酯(Triglyceride,TG),应用直接法测定高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(Low density lipoprotein cholesterol,LDL-C),应用偶氮砷Ⅲ法测定钙(Calcium,Ca),应用磷钼酸盐法测定磷(Phosphorus,P),应用NPP底物-AMP缓冲液法测定碱性磷酸酶(Alkaline phosphatase,ALP)。采用双能X线BMD仪测量BMD,使用改良的骨折风险评估工具(Fracture Risk Assessment Tool,FRAX)评估未来10年主要部位骨质疏松性骨折风险(Major osteoporotic fracture,MOF)及髋部骨折风险(Hip fracture,HF)。应用SPSS 26.0进行统计分析。

结果

1. 基线资料显示, 与1.14<FCP≤1.73 ng/ml和FCP>1.73ng/ml两组T2DM患者相比,FCP≤1.14ng/ml组T2DM患者的病程更长,HbA1c更高,FIns更低,BMI更小,降糖药物胰岛素及其类似物使用率更高,血Ca水平更低,糖尿病视网膜病变(Diabetic retinopathy,DR)发病率更高,全身(Whole body,WB) BMD、腰椎(Lumbar spine, LS) BMD更低,HF以及既往脆性骨折发病率更高(P<0.05)。性别、年龄、吸烟史、饮酒史、FPG 、Cr、TC、TG、HDL-C、LDL-C、糖尿病周围神经病变(Diabetic peripheral neuropathy,DPN)、糖尿病肾病(Diabetic nephropathy,DN)、糖尿病周围血管病(Diabetic peripheral angiopathy,DPA)、P、ALP、25(OH)D、PTH、β-CTX、PⅠNP、股骨颈(Femoral neck,FN) BMD、MOF、降糖药物使用率(胰岛素促泌剂、钠⁃葡萄糖协同转运蛋白2(Sodium⁃glucose co⁃transporter 2,SGLT2)抑制剂、双胍类、α-葡萄糖苷酶抑制剂、二肽基肽酶4(Dipeptidyl peptidase 4,DPP-4)抑制剂、胰高血糖素样肽-1(Glucagon-like peptide-1,GLP-1)受体激动剂)三组间比较差异无统计学意义(P>0.05)。

2. Spearman相关分析显示,总人群中,FCP与脆性骨折发病率呈负相关(P<0.05),与WB BMD、LS BMD、FN BMD、MOF及HF均无相关性(P>0.05)。但是FCP水平三分位分层研究发现,FCP≤1.14ng/ml组,FCP与WB BMD、LS BMD、FN BMD呈正相关,与骨折风险、脆性骨折发病率呈负相关(P<0.05);然而在1.14<FCP≤1.73ng/ml和FCP>1.73ng/ml组,FCP与BMD、骨折风险以及脆性骨折发病率均无相关性(P>0.05)。

3.  按FCP水平三分位分层回归分析显示,FCP≤1.14ng/ml的T2DM患者,随着FCP水平升高,WB BMD、LS BMD、FN BMD升高,骨折风险、既往脆性骨折发病率降低(P<0.05);1.14<FCP≤1.73ng/ml和FCP>1.73ng/ml的T2DM患者,FCP水平与WB BMD、LS BMD、FN BMD、骨折风险和脆性骨折发病率均无相关性(P>0.05)。

进一步校正模型回归分析显示,FCP≤1.14ng/ml的T2DM患者,FCP水平与WB BMD、LS BMD、FN BMD呈正相关(P<0.05),与骨折风险、脆性骨折发病率呈负相关,FCP是BMD、骨折风险和脆性骨折的独立影响因素(P<0.05);1.14<FCP≤1.73ng/ml和FCP>1.73ng/ml两组T2DM患者,FCP水平与BMD、骨折风险和脆性骨折发病率均无相关性(P>0.05)。

4. 按病程分层模型回归分析显示,T2DM病程≥10年的患者,随着FCP水平升高,骨折风险、既往脆性骨折发病率降低,FCP水平与WB BMD呈正相关(P<0.05);T2DM病程<10年的患者,FCP水平与WB BMD、LS BMD、FN BMD、骨折风险和脆性骨折发病率均无相关性(P>0.05)。

结论

1.FCP水平三分位分组后临床基线资料显示,FCP水平不同的三组WB BMD、LS BMD、HF、脆性骨折发病率有显著差异。

2.T2DM患者BMD与FCP水平无明显相关性,FCP水平分层后,FCP≤1.14 ng/ml组T2DM患者,FCP水平与BMD呈正相关,而另外两组T2DM患者FCP水平与BMD无相关性。骨折风险预测与FCP的相关性与上述一致。

3.T2DM患者FCP水平与脆性骨折发病率呈负相关,FCP水平分层后,FCP≤1.14 ng/ml组T2DM患者FCP水平与脆性骨折发病率仍呈负相关,但是另外两组T2DM患者FCP水平与脆性骨折发病率无相关性。

4.按病程进行亚组分析,T2DM病程≥10年的患者,FCP与WB BMD呈正相关,与骨折风险、脆性骨折发病率呈负相关。病程<10年的T2DM患者中,FCP与BMD、骨折风险及脆性骨折发病率无明显相关性。

5.回归分析显示FCP≤1.14 ng/ml组T2DM患者,FCP是BMD、骨折风险和脆性骨折的独立影响因素。结果提示FCP水平对部分T2DM患者骨质疏松的发生有一定的预测价值。

Other Abstract

Objective

Previous researches shown that C-peptide had no biological activity, but recent studies have shown that C-peptide has a certain impact on diabetic complications and bone metabolism. Therefore, this study explored the correlation between C-peptide and bone mineral density (BMD), fracture risk in patients with type 2 diabetes (T2DM), and then revealed the clinical predictive value of C-peptide on diabetic osteoporosis and fracture risk.

Methods

540 T2DM patients from the First Hospital of Lanzhou University were enrolled and divided into three groups according to fasting C-peptide (FCP) tertiles: FCP ≤ 1.14ng/ml group, 1.14 < FCP ≤ 1.73 ng/ml group and FCP > 1.73ng/ml group. Clinical data were collected, including: gender, age, T2DM duration, T2DM complications, smoking, drinking, medication usage, parents' hip fracture history, previous disease history, and body mass index (BMI).

Parathyroid hormone (PTH), 25 hydroxy vitamin D [25(OH)D], procollagen type Ⅰ N-propeptide (PⅠNP) and β isomer of C-terminal telopeptide of type Ⅰ collagen (β-CTX) were measured by electrochemiluminescence immunoassay. Fasting insulin (FIns) and FCP were measured by chemiluminescence. Glycosylated hemoglobin (HbA1c) was measured by high-performance liquid chromatography. Fasting plasma glucose (FPG) was measured by glucose oxidase method. Creatinine (Cr) was measured by sarcosine oxidase method. Total cholesterol (TC) was measured by CHOD-PAP method. Triglyceride (TG) was measured by GPO-PAP method. High density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured by direct method. Calcium (Ca) was measured by arsenazo Ⅲ method. Phosphorus (P) was measured by phosphomolybdate method. Alkaline phosphatase (ALP) was measured by NPP substrate-AMP buffer method. BMD was measured by dual-energy X-ray absorptiometry, and the ten year probability of major osteoporotic fracture (MOF) and hip fracture (HF) were calculated by adjusted Fracture Risk Assessment Tool (FRAX). SPSS 26.0 was used for statistical analysis.

Results

1. Compared with T2DM patients in 1.14 < FCP ≤ 1.73 ng/ml group and FCP > 1.73ng/ml group, T2DM patients in  FCP ≤ 1.14ng/ml group had longer duration, higher HbA1c, lower FIns, smaller BMI, higher usage of insulin and its analogues, lower serum Ca, higher risk of diabetic retinopathy (DR), and lower BMD of whole body (WB) and lumbar spine(LS), higher HF, and lower incidence of previous fragility fractures (P<0.05). Sex, age, smoking, drinking, FPG, Cr, TC, TG, HDL-C, LDL-C, diabetic peripheral neuropathy (DPN), diabetic nephropathy (DN), diabetic peripheral angiopathy (DPA), P, ALP, 25(OH)D, PTH, β-CTX, PⅠNP, femoral neck (FN) BMD, MOF, usage of hypoglycemic drugs [insulin secretagogues, sodium-glucose co-transporter 2 (SGLT2) inhibitors, biguanides, α-glucosidase inhibitors, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists] had no significant difference among three groups.

2. Spearman correlation analysis showed that FCP was negatively correlated with fragility fractures, but not with WB BMD, LS BMD, FN BMD, MOF and HF in all patients (P > 0.05). According to FCP tertiles, in FCP ≤ 1.14ng/ml group, FCP was positively correlated with WB BMD, LS BMD and FN BMD, and negatively correlated with fracture risk and fragility fractures, but in 1.14 < FCP ≤ 1.73 ng/ml and FCP > 1.73ng/ml group, FCP was not correlated with BMD, fracture risk and fragility fractures (P > 0.05).

3. According to regression analysis stratified by FCP tertiles, WB BMD, LS BMD, FN BMD increased, fracture risk and previous fragility fractures incidence decreased with the increase of FCP level in T2DM patients with FCP ≤ 1.14ng/ml. However, FCP was not correlated with WB BMD, LS BMD, FN BMD, fracture risk and history of fragility fractures in T2DM patients with FCP ≤ 1.73 ng/ml and FCP > 1.73ng/ml.

Furthermore, adjusted model regression analysis showed that FCP levels were positively correlated with WB BMD, LS BMD, FN BMD (P < 0.05), but negatively correlated with fracture risk and incidence of fragility fracture in T2DM patients with FCP ≤ 1.14ng/ml. FCP was an independent influencing factor for BMD, fracture risk and fragility fracture (P <0.05); but in T2DM patients with 1.14 < FCP ≤ 1.73ng/ml and FCP > 1.73ng/ml, FCP was not related to BMD, fracture risk and incidence of fragility fracture (P > 0.05).

4. According to regression analysis stratified by duration of T2DM, fracture risk and fragility fractures incidence decreased with the increase of FCP level in T2DM patients with duration ≥ 10 years, and FCP level was positively associated with WB BMD (P < 0.05), but there was no correlation between FCP level and WB BMD, LS BMD, FN BMD, fracture risk and fragility fractures in T2DM patients with duration < 10 years (P > 0.05).

Conclusions

1. Grouped by FCP tertiles, clinical baseline data showed significant differences in WB BMD, LS BMD, HF, and fragility fractures among three groups.

2. There is no significant correlation between BMD and FCP level in T2DM patients. After stratification of FCP level, there was a positive correlation between FCP level and BMD in T2DM patients with FCP ≤ 1.14 ng/ml, while there was no correlation between FCP level and BMD in the other two groups. The correlation between fracture risk prediction and FCP is consistent with the above.

3. There is a negative correlation between FCP level and incidence of fragility fractures in T2DM patients. After stratification of FCP level, FCP was still negatively correlated with incidence of fragility fractures in T2DM patients with FCP ≤ 1.14 ng/ml, while there was no correlation between FCP level and BMD in the other two groups.

4. Subgroup analysis stratified by duration, T2DM patients with duration ≥ 10 years, FCP was positively correlated with WB BMD, while it was negatively correlated with fracture risk and incidence of fragility fractures. In T2DM patients with duration < 10 years, there was no significant correlation between FCP and BMD, fracture risk, or fragility fracture.

5. Regression analysis showed that in T2DM patients with FCP ≤ 1.14 ng/ml, FCP was an independent influencing factor for BMD, fracture risk, and fragility fractures. It suggests that FCP have a certain predictive value for the occurrence of osteoporosis in some T2DM patients.

Subject Area内分泌与代谢病
MOST Discipline Catalogue医学 - 临床医学 - 内科学
URL查看原文
Language中文
Other Code262010_220200906560
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/537405
Collection第一临床医学院
Affiliation
兰州大学第一临床医学院
Recommended Citation
GB/T 7714
杨虹. 2型糖尿病C肽水平与骨密度、骨折风险相关性研究[D]. 兰州. 兰州大学,2023.
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