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超重、肥胖对2型糖尿病患者凝血及代谢指标的影响

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作者:徐锦春1,陈思娇1, 王大南1,2, 陈 婕1, 胡 怡1, 宋今丹2    作者单位:1.中国医科大学附属第一医院干部医疗工作部老年病教研室, 辽宁,沈阳,110001;2.中国医科大学医学分子生物学研究所,卫生部细胞生物学重点实验室 

【摘要】  目的:了解超重、肥胖对2型糖尿病患者凝血及代谢紊乱的影响。方法:选择初诊为2型糖尿病的患者248例,根据人体质量指数(BMI)分为正常BMI对照组(95例)、超重组(87例)、肥胖组(66例),均测定血脂、血糖、空腹胰岛素等相关指标, 计算胰岛素抵抗指数(HOMA-IR),并进行统计学处理。结果:与正常BMI对照组相比,超重组、肥胖组血浆纤维蛋白原(fg)[(3.37±0.55) g/L比(4.04±0.70) g/L比(5.20±0.69) g/L]、尿微量白蛋白(UMA)[ (14.46±8.90) mg/g比(47.33±42.54) mg/g比(104.45±60.78) mg/g]、空腹血糖(FBG)[(7.15±0.97) mmol/L比(8.84±1.81) mmol/L比(10.06±2.28) mmol/L]、空腹胰岛素(FINS)[(10.09±8.21) IU/ml比(14.33±15.55) IU/ml比(19.69±10.86) IU/ml]、HOMA-IR[(3.19±2.59)比(5.51±5.38)比(8.48±4.62)]及血甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)水平均明显升高,且随肥胖程度的增加而呈上升趋势,而血浆凝血酶原时间(PPT) [(13.33±0.69) s比(12.74±0.69)s比(11.43±0.53)s]、血浆活化部分凝血活酶时间(APTT)[(37.32±2.31) s比(36.55±2.41) s比(34.61±1.53) s]、HDL-C[(1.54±1.12) mmol/L比(1.27±0.41) mmol/L比(1.09±0.28) mmol/L]水平均明显降低,且随肥胖程度的加深而呈下降趋势(P均<0.05)。结论:超重及肥胖加重2型糖尿病凝血功能及代谢障碍,并加重胰岛素抵抗的程度,且此异常随肥胖程度的加深而更加严重。

【关键词】  糖尿病,2型;肥胖症;凝血酶原;高脂血症

 Abstract:Objective:To study influence of overweight and obesity on blood coagulation and metabolic disorders in patients with type 2 diabetes mellitus (T2DM). Methods: total of 248 preliminary diagnosed T2DM patients were selected. According to body mass index (BMI), they were divided into normal BMI control group (n=95), overweight group (n=87) and obesity group (n=66). Blood lipids, blood glucose and fasting insulin (FINS) were measured in all patients and homeostasis model-insulin resistance index (HOMA-IR) was calculated then. Statistical analysis was performed. Results:Compared with normal BMI control group, there were significant increase in fibrinogen [(3.37±0.55) g/L vs. (4.04±0.70) g/L vs. (5.20±0.69) g/L], urine microalbumin [(14.46±8.90) mg/g vs. (47.33±42.54) mg/g vs. (104.45±60.78) mg/g], fasting blood glucose [ (7.15±0.97) mmol/L vs. (8.84±1.81) mmol/L vs. (10.06±2.28) mmol/L], FINS [(10.09±8.21) IU/ml vs. (14.33±15.55) IU/ml vs. (19.69±10.86) IU/ml], HOMA-IR[(3.19±2.59) vs. (5.51±5.38) vs. (8.48±4.62)], TG, TC and LDL-C levels in overweight group and obesity group, and the more BMI patients were, the higher these indicators were; There were significant decrease in plasma prothrombin time [(13.33±0.69)s vs. (12.74±0.69)s vs. (11.43±0.53)s], activated partial thromboplastin time [ (37.32±2.31)s vs. (36.55±2.41)s vs. (34.61±1.53)s] and HDL-C [(1.54±1.12) mmol/L vs. (1.27±0.41) mmol/L vs. (1.09±0.28) mmol/L] in overweight group and obesity group(P<0.05 all). Conclusion:Overweight and obesity aggravate coagulation and metabolic disorders in patients with type 2 diabetes mellitus. It also aggravates degree of insulin resistance, the more BMI patients are, the more serious they are.

  Key words:Diabetes mellitus, type 2; Obesity; Blood lipid; Hyperlipidemia

  Overweight or obese populations have become high risk populations of diabetes mellitus (DM). In recent years, percentage of these populations rapidly increase both in domestic and abroad. DM has become the third major non-infectious reason of death following cancer and cardiovascular diseases in the world. In order to study influence of overweight and obesity on DM patients, the present study mainly focused on relative indexes of blood coagulation and metabolism in DM patients. Research consequence is reported below.

  1 Subjects and methods

  1.1 Subjects

  A total of 248 patients with preliminary diagnosed type 2 DM (T2DM) from Jan 2008 to Dec 2008as were divided into normal body mass index(BMI)control group [95 patients, there were 54 males and 41 females with age 40~75 (62.89±9.79) years old and BMI (22.08±1.45) kg/m2], overweight group [87 patients, there were 46 males and 41 females with age 40~75 (60.15±9.51) years old and BMI (25.79±1.21) kg/m2], obesity group [66 patients, there were 34 males and 32 females with age 40~75 (60.70±6.15) years old and BMI (29.44±1.77) kg/m2] according BMI. Diagnostic criteria for T2DM accorded with the criteria formulated by WHO DM committee of experts in 1999. Diagnostic criteria for overweight and obesity was accorded with Prevention and control guidelines of overweight and obesity for Chinese adults (2003), that is, normal weight: 18.5~23.9 kg/m2; overweight: 24.0~27.9 kg/m2; obesity: BMI≥28 kg/m2. Homeostasis model-insulin resistance index (HOMA-IR) = [fasting insulin (FINS) × fasting blood glucose (FBG)]/22.5. Exclusion criteria: 1. Patients with pathological overweight and obesity, or had a history of weight loss recently; 2. Secondary hypertension; 3. Severe brain or liver complications; 4. Endocrine diseases of hypophysis and thyroid gland which can influence lipid metabolism; 5. Heart failure, myocardial infarction and unstable angina pectoris; 6. Peripheral vascular disease; 7. Chronic nephrosis and uremia; 8. Patients who were taking hypoglycemic, lipid-lowering, anti-platelet or fibrinogen-lowering drugs, or patients with other diseases influencing coagulation and fibrinolysis. There were no significant difference in age, gender and level of blood pressure among three groups (P>0.05).

  1.2 Methods

  All patients received measurements of plasma fibrinogen (fg), plasma prothrombin time (PPT), activated partial thromboplastin time (APTT), urine microalbumin (UMA), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG) and FINS, and HOMA-IR was calculated then.

  1.3 Statistical process

  SPSS 17.0 software was used to perform statistical process. Measurement data were presented as mean ± standard deviation(x-±s). Analysis of variance was used to perform comparison of variables among three groups. For those with homogeneity of variance, multiple mean pairwise comparison t test was used; for those with heterogeneity of variance, approximate t test was used. P<0.05 was regard as possessing significant difference.

  2 Results

  2.1 Influence of overweight and obesity on coagulation index in T2DM patients

  Compared with normal BMI control group, fg level significantly increased in overweight group and obesity group and its level increased along with the increased of BMI degree; Levels of PPT and APTT significantly decreased in overweight group and obesity group and their levels decreased along with the increased of BMI degree, were shown in table 1, indicated that overweight and obesity can aggravate hypercoagulation and decrease anti-coagulation and fibrinolysis function in T2DM patients.

  2.2 Influence of overweight and obesity on metabolism indexes in T2DM patients

  Compared with normal BMI control group, levels of UMA, TG, TC and LDL-C significantly increased in overweight group and obesity group and their levels increased along with the increased of BMI degree; HDL-C level significantly decreased in overweight group and obesity group and its level decreased along with the increased of BMI degree, were shown in table 2, indicated that overweight and obesity can aggravate metabolic disorder in T2DM patients.

  2.3 Influence of overweight and obesity on blood glucose and HOMA-IR in T2DM patients

  Compared with normal BMI control group, levels of FBG, FINS and HOMA-IR significantly increased in overweight group and obesity group and their levels increased along with the increased of BMI degree, were shown in table 3, indicated that overweight and obesity can aggravate the degree of insulin resistance.Table 1 Comparison of blood coagulation indexes among three groupsTable 2 Comparison of metabolic indexes among three groupsTable 3 Comparison of blood glucose, FINS and HOMA-IR among three groups

  3 Discussion

  With change of diet structure and reduction of physical activities in life style, prevalence rates of overweight and obesity rapidly increase among adults and children in either developed countries or developing countries, especially in country with developed or rapid developing economy. Some evidence has prove that overweight and obesity are important risk factors for cardiovascular diseases, DM, some cancers and some other chronic diseases. DM complicated with obesity exacerbates complications, bringing a heavy burden to families and the society.

  Obesity is an inflammatory state in human. It may play an important role in pathogenesis of insulin resistance (IR) as an inflammatory mechanism. In obese patients, adipose tissue over expresses tumor necrosis factor (TNF)-α, leading to the activation of nuclear factor (NF)-кB, which further increases expression of TNF-α and makes inflammatory process become to cascading [1]. Reduction of adiponectin secretion, increase of secretion of inflammatory cytokines, such as interleukin (IL)-6, IL-8, TNF-α and monocyte chemoattractant protein (MCP)-1, and inflammatory state of adipose tissue cause IR. Obesity aggravates originally existed IR in DM through adipocytokines' secretion disorders, ectopic deposition of lipids, lipotoxicity of free fatty acids, dysfunction of peroxisome proliferator-activated receptors, decrease of endothelial diastolic function, social and psychological stress, intra-abdominal fat accumulation and increased level of cortisol [2].

  The fg is not only a kind of blood coagulation factor, but also an inflammatory marker, and it is an acute phase protein which is synthesized in liver by replying to the IL-6 in circulation. As blood coagulation factor Ⅰ, fg is the main substance that participates in hematischesis and thrombogenesis, its level increase can aggravate blood coagulation. PPT reflects concentrations of blood coagulation factor Ⅰ, Ⅱ, Ⅴ, Ⅶ and Ⅹ. APTT is used to measure vitality of endogenous pathway coagulation factor Ⅻ, Ⅺ, Ⅸ and Ⅷ, and it is also influenced by coagulation factorⅠ, Ⅱ, Ⅴ and Ⅹ at the same time. Shortening of PT and APTT indicates that blood is in hypercoagulable state,can induce a series of blood coagulation disorder.

  Obesity can lead to oxygen radicals increase and antioxidant defense function weaken, causes oxidative stress which leads to further damage to pancreatic islet, strengthen IR, elevates blood glucose level and leads to peroxide of lipids, accelerating occurrence of diabetic macrovascular complications.

  Obesity can also cause kidney injury, leading to proteinuria, glomerulus hypertrophia and cirrhosis. Kidney injury occultly occurs, which only presents as increase of glomerular filtration rate and microalbuminuria(MAU)in early period. MAU not only indicates glomerular injury, but also participates in direct or indirect damage to intrinsic renal cells (glomerular endothelial cells, podocytes, mesangial cells and renal tubular epithelial cells) [3].

  In summary, overweight can cause abnormal blood coagulation and metabolism, exacerbates DM and its influence correlated with BMI degree. Therefore, for T2DM patients, treatment no only should be to control blood glucose, also should be to reduce weight, decrease negative effect of overweight.

【参考文献】
    [1]胡 怡, 陈思娇, 宋今丹. FOXC2应用于代谢综合征的前景展望[J].中国糖尿病杂志, 2009, 17(12): 955-957.

  [2] 邹大进, 吴 鸿. 胰岛素抵抗与肥胖的关系认识[J]. 诊断学理论与实践, 2009, 8(3): 237-239.

  [3] 陈 楠, 陈佳韵. 重视微量白蛋白尿的筛查与诊治[J].实用医院临床杂志, 2005, 2(1): 17-19.

  [4]张 勤,吴 桐,庄建军,等.肥胖对2型糖尿病患者左室舒张功能的影响[J].心血管康复医学杂志,2006,15(6):533-535.

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