中国东北汉族人群解偶联蛋白3基因-55C/T多态性与2型糖尿病相关性研究

目的探讨解偶联蛋白3(uncoupling protein 3,UCP3)基因-55C→T变异与中国东北地区2型糖尿病的关系。方法用聚合酶链反应-限制性片段长度多态性检测100例2型糖尿病患者(男/女为58/42)及113名糖耐量正常者(男/女为56/57)UCP3基因-55C→T变异的基因型。结果 2型糖尿病组与正常对照组三种基因型频率及等位基因频率分布差异均有显著性意义,P值分别为0.027和0.003,两组间携带T的基因型(CT+TT)频率差异有显著意义(P=0.008);T等位基因与2型糖尿病患者血清总胆固醇(CHOL)及低密度脂蛋白(LDLC)频率升高相关(P为0.021,0.024)。结论 UCP3基因-55C→T变异与中国东北汉族人群2型糖尿病患者局部体脂代谢存在相关性,该基因变异与2型糖尿病发病相关。     

Aldose reductase gene polymorphisms and peripheral nerve function in patients with type 2 diabetes

OBJECTIVE: We screened the human aldose reductase (ALR) gene for DNA sequence variants in type 2 diabetic and nondiabetic subjects and investigated whether the previously reported and novel polymorphisms were associated with neurophysiologic deterioration and clinical peripheral neuropathy. RESEARCH DESIGN AND METHODS: The study population included 85 Finnish type 2 diabetic and 126 nondiabetic subjects. The genetic analyses were performed using the PCR, single-strand conformation polymorphism, restriction fragment-length polymorphism, and automated laser fluorescence scanning analyses. A detailed neurologic examination and neurophysiologic analyses were performed at the time of diagnosis and at the 10-year examination. RESULTS: The genetic screening identified four polymorphisms: C-106T, C-11G, A11370G, and C19739A. The C and Z-2 alleles of the C-106T polymorphism and the previously reported (CA)(n) repeat marker were more frequent in type 2 diabetic subjects than in nondiabetic subjects. At baseline, the diabetic subjects with the T allele of the C-106T polymorphism had lower sensory response amplitude values in the peroneal (P = 0.025), sural (P = 0.007), and radial (P = 0.057) nerves and, during follow-up, a greater decrease in the conduction velocity of the motor peroneal nerve than those with the C-106C genotype. No associations were found between the polymorphisms examined and clinical polyneuropathy. CONCLUSIONS: The C-106T polymorphism of the ALR gene may contribute to an early development of neurophysiologic deterioration in type 2 diabetic patients.     

Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with a reduced prevalence of diabetic neuropathy in patients with type 2 diabetes

OBJECTIVE: To establish whether single nucleotide polymorphisms (Asp299Gly and Thr399Ile) of the toll-like receptor 4 have an association with late diabetic complications. RESEARCH DESIGN AND METHODS: The study was conducted in 246 type 1 and 530 type 2 diabetic patients. The alleles of both polymorphisms were detected using PCR and subsequent cleavage by NcoI and HinfI restriction endonucleases. RESULTS: No difference was found between type 1 and type 2 diabetic patients in the prevalence of alleles of the Asp299Gly and Thr399Ile polymorphisms. In most cases, the alleles Gly299 and Ile399 occurred in a co-segregatory manner. The prevalence of the Gly299/Ile399 haplotype was 10.6 and 12.1% in type 1 and type 2 diabetic patients, respectively (P = 0.63). No association with diabetic nephropathy or diabetic neuropathy was found in type 1 diabetic patients. In type 2 diabetic patients, however, heterozygote carriers of the Asp299Gly and Thr399Ile genotypes had a significantly reduced prevalence of diabetic neuropathy (odds ratio 0.35 [95% CI 0.19-0.61]; P = 0.0002); no association with diabetic nephropathy was found. CONCLUSIONS: Our data indicate that Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with reduced prevalence of diabetic neuropathy in type 2, but not in type 1, diabetes. Thus different mechanisms may be involved in the pathophysiology of diabetic neuropathy in type 1 and type 2 diabetes.     

Association of an Osteopontin gene promoter polymorphism with susceptibility to diabetic nephropathy in Asian Indians

Genetic predisposition has been proposed to be a major determinant in the development of renal complications of diabetes. Osteopontin (OPN) has been suggested to be associated with renal diseases characterized by tubulointerstitial fibrosis and proteinuria. However, information on association of genetic polymorphisms in OPN with diabetic nephropathy is lacking. Thus, the present study was designed with the aim to examine the association of an OPN gene promoter polymorphism with diabetic nephropathy in Asian Indians. OPN C-443T (rs11730582) polymorphism was determined in 1115 type 2 diabetic patients belonging to two independently ascertained cohorts using Real time PCR based Taqman assay. We observed a nearly threefold elevated risk of diabetic nephropathy among carriers of T allele and TT genotype of OPN C-443T polymorphism. Further, this allele was found to be significantly associated with proteinuria and lower eGFR, a hallmark of diabetic nephropathy, in both our cohorts. This is the first study which suggests that OPN C-443T polymorphism may be a significant risk factor for diabetic nephropathy in type 2 diabetic patients.     

解偶联蛋白2启动子-866G／A多态性与中国北方儿童肥胖病相关性研究

目的：研究解偶联蛋白2（UCP2）基因启动子-866G/A单核苷酸多态性与中国北方儿童肥胖病遗传发病机制的相关性。方法病例组选取2010年1～9月于北京儿童医院内分泌科就诊且无血缘关系的儿童肥胖病患者220例。对照组选自无血缘关系的成年健康献血员220例。用血液基因组DNA提取试剂盒提取外周血基因组DNA,UCP2基因启动子-866G/A单核苷酸多态性分析采用PCR-RFLP法,并选取部分标本进行测序分析。结果（1）UCP2基因启动子-866A等位基因在中国肥胖病儿童中的频率与正常对照组相近,无统计学差异（44．8％ vs．46．4％,χ2＝0.224,P＝0.685）。（2）GG、GA和AA基因型在患者频率分布为34．5％、41．4％及24．1％;在对照组中的分布为27．3％、52．7％及20.0％,三者在患者与对照中的频率分布无显著性差异（ P＞0.05）。包含等位基因A的基因型AA和GA基因型频率之和在对照组中的频率增加,但无统计学差异（65．5％vs．72.7％,P＝0.122）。按性别进行分层分析,肥胖病男童与对照组的基因型频率分布尚无显著性差异（ P＝0.05）,在女童中亦无显著性差异（ P＝0.512）。结论 UCP2基因启动子-866 G/A单核苷酸多态性与中国儿童肥胖病遗传发病机制未见显著相关性。 UCP2基因启动子-866 G/A多态性与肥胖病的遗传发病机制的相关性存在一定的人种差异。     

醛糖还原酶和内皮型一氧化氮合酶基因多态性并存与糖尿病肾病发病的相关性

背景有关资料显示,醛糖还原酶基因启动子区C-106T多态和内皮型一氧化氮合酶基因第七外显子GLU298ASP(894G→T)多态与糖尿病肾病有关,上述基因多态并存时,2型糖尿病患者糖尿病肾病的发病风险是否明显增加有待进一步研究.目的探讨染色体7q35区醛糖还原酶基因启动子区C-106T多态和内皮型一氧化氮合酶基因第七外显子GLU298ASP(894G→T)多态并存时与中国北方汉族人群糖尿病肾病发病的关系.设计病例-对照,对比观察.单位青岛大学医学院附属医院内分泌科.对象选择2002-11/2005-04在青岛大学医学院附属医院内分泌科住院2型糖尿病患者139例,男54例,女85例,年龄(64±8)岁.符合1999年世界卫生组织关于糖尿病诊断和分类标准.根据24 h尿微量白蛋白排泄率分为2组糖尿病肾病组61例和非糖尿病肾病组78例.选择同期本院体检健康成人63名为对照组,男24名,女39名;年龄50～78 岁.纳入对象均为汉族,且对检测项目知情同意.方法运用聚合酶链反应限制性片段长度多态性技术、DNA测序技术及琼脂糖凝胶电泳分离技术检测纳入对象的醛糖还原酶基因启动子区C-106T多态位点和内皮型一氧化氮合酶基因第7外显子GLU298ASP(894G→T)多态位点的等位基因和基因型.主要观察指标①醛糖还原酶和内皮型一氧化氮合酶基因多态性.②糖尿病肾病危险因素的多元逐步回归分析结果.③醛糖还原酶C-106T多态和内皮型一氧化氮合酶894G→T多态与糖尿病肾病相对危险度.结果2型糖尿病患者139例和健康人63名全部进入结果分析.①糖尿病肾病组内皮型一氧化氮合酶基因第7外显子894G→T多态位点的T等位基因和TG基因型频率明显高于非糖尿病肾病组和对照组(χ2=8.261,19.629,P＜0.01).②糖尿病肾病组醛糖还原酶基因启动子区C-106T多态位点的T等位基因和CT基因型频率明显高于非糖尿病肾病组和对照组(χ2=6.343,8.940,P＜0.05,0.01).③将上述基因多态联合分析发现,糖尿病肾病组的TG/CT基因型频率明显高于非糖尿病肾病组和对照组(χ2=6.972,P＜0.01);GG/CC基因型频率显著低于非糖尿病肾病组和对照组(χ2=13.304,P＜0.01).④糖基化血红蛋白、收缩压、总胆固醇、内皮型一氧化氮合酶基因的第七外显子894G→T多态及醛糖还原酶基因启动子区C-106T多态均是糖尿病肾病的独立危险因素(Wald=5.627,4.92,P＜0.05).⑤GG/CC基因型可能是糖尿病肾病的保护基因型(OR=0.25,P＜0.01);GG/CT或TG/CC基因型携带者糖尿病肾病的危险性增加2.3倍,TG/CT基因型携带者糖尿病肾病的危险性增加4.8倍.结论内皮型一氧化氮合酶基因第7外显子894G→T多态位点的T等位基因和TG基因型和醛糖还原酶基因启动子区C-106T多态位点的T等位基因和CT基因型增加2型糖尿病患者发生糖尿病肾病的危险性,两种基因多态并存时,糖尿病肾病的发病风险明显增加.     

Uncoupling protein 2 promoter polymorphism -866G/A affects peripheral nerve dysfunction in Japanese type 2 diabetic patients

OBJECTIVE: To determine genetic predispositions for diabetic polyneuropathy, we investigated the relationship between the -866G/A polymorphism of uncoupling protein (UCP) 2 and neurological manifestations in 197 type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We first examined whether UCP2 mRNA had been expressed in the dorsal root ganglion (DRG) in four Long-Evans Tokushima Otsuka rats using RT-PCR and electrophoresis. Genotyping of UCP2 promoter polymorphism -866G/A was then performed in 197 unrelated Japanese type 2 diabetic patients, who were subjected to nerve conduction, quantitative vibratory perception, head-up tilt, and heart rate variability tests, by PCR restriction fragment-length polymorphism. The relationships between UCP2 genotype and various nerve functions were analyzed by uni- and multivariable analysis. RESULTS: Expression of UCP2 mRNA was confirmed in rat DRG. Multiple regression analysis clarified the hypothesis that the G/A + A/A genotype was significantly related to decreased motor nerve conduction velocity and impaired blood pressure maintenance on the head-up tilt test. Multiple logistic regression analysis revealed that the G/A + A/A genotypes are a significant risk factor for sensory nerve conduction slowing and orthostatic hypotension. CONCLUSIONS: UCP2 promoter gene polymorphism -866 G/A was significantly associated with nerve conduction slowing and vasomotor sympathetic functions. These findings suggest that the higher UCP2 activity related to the A allele has an energy-depleting effect on peripheral nerve function in type 2 diabetic patients.     

Decline in neurophysiological function after 7 years in an adolescent diabetic cohort and the role of aldose reductase gene polymorphisms

OBJECTIVE: This 7-year longitudinal study examines the potential impact of aldose reductase gene (AKR1B1) polymorphisms on the decline of nerve function in an adolescent diabetic cohort. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes (n = 262) were assessed with three cardiovascular autonomic tests (heart rate variation during deep breathing, Valsalva maneuver, and during standing from a lying position) and pupillometry (resting pupil diameter, constriction velocity, and reflex amplitude), thermal, and vibration thresholds on the foot. Genotyping was performed for promoters (C-106T and C-12G), (CA)(n) dinucleotide repeats, and intragenic BamH1 polymorphism. RESULTS: Median time between first and last assessment was 7.0 years (interquartile range 5.1-11.1), with a median of five assessments (four to seven) per individual. At first assessment, median age was 12.7 years (11.7-13.9), median duration was 5.3 years (3.4-8.0), and median HbA(1c) was 8.5% (7.8-9.3). All tests declined over time except for two cardiovascular autonomic tests and vibration discrimination. Faster decline in maximum constriction velocity was found to associate with the Z-2 allele (P = 0.045), Z-2/Z-2 (P = 0.026). Slower decline in hot thermal threshold discrimination associated with Z+2 (P = 0.044), Z+2/Z+2 (P < 0.0005), Z+2/T (P = 0.038), and bb (P = 0.0001). CONCLUSIONS: Most autonomic and quantitative sensory nerve testings declined over time. AKR1B1 polymorphisms were strongly associated with the rate of decline of these complications.     

血管紧张素原基因部分多态性指标与原发性高血压的发病风险:社区病例对照

背景:血管紧张素原基因是第一个被发现的原发性高血压候选基因,T174M5和M235T多态均位于AGT基因第二外显子,且存在连锁不平衡。启动子区域A-6G和G-217A位点多态对其基因表达起重要调节作用,且血管紧张素原基因的表达产物与血压水平的维持密切相关。目的:探讨血管紧张素原基因A-6G,T174M和G-217A位点多态性与中国汉族人群原发性高血压发病风险的关系。设计:整群抽样,病例-对照分析。单位:南京医科大学第一附属医院老年医学科与心血管科,国家人类基因组南方研究中心,江苏省东台市人民医院心血管科。对象:实验于2005-09/10在江苏省东台市农村完成。①263例实验对象均来自江苏省盐城市东台县农村,其中原发性高血压组177例为未经药物治疗的原发性高血压患者,高血压的诊断参照1999年WHO/ISH高血压诊断标准(收缩压≥140mmHg和/或舒张压≥90mmHg);正常对照组86例。②纳入标准:实验对象为汉族;长期居住本地非外来人口;能清楚回答问题;经病史、临床症状、体征及辅助检查确诊;统一问卷面访调查资料完整。③排除标准:原发性高血压组排除继发性高血压,正常对照组排除高血压家族史,同时两组人群均排除肝、肾慢性疾病和糖尿病。方法:采集外周静脉血3mL,用FlexiGeneDNAKit(250)提取人外周血中DNA。应用primer3软件进行引物设计,并排除引物序列中的多态位点。多重聚合酶链反应扩增后,取3μL反应产物用琼脂糖凝胶电泳检测扩增结果,扩增成功的聚合酶链反应产物用QIAquickPCRPurifica-tionKit纯化,纯化后的产物用DNaseⅠ片段化,片段化的酶切产物以脱氧核苷酸末端转移酶进行荧光素标记。每个单核苷酸多态各设计2条等位基因特异性探针和1条错配探针,芯片用OmniGridTM100点样仪制备,每个探针重复3次,形成3个阵列。杂交液95℃变性10min后,立即置于冰上冷切,取10μL杂交液加入到芯片矩阵上,50℃杂交2h,然后洗涤,甩干。GenePix4000B共聚焦激光扫描仪进行芯片扫描,利用GenePixPro提取得到每条探针的荧光信号强度值,通过计算每个单核苷酸多态的等位基因分数判断基因型。主要观察指标:①两组血管紧张素原基因各多态位点基因型分布频率的比较。②血管紧张素原基因A-6G和T174M位点多态性与原发性高血压发病风险的相关分析。③两组血管紧张素原基因A-6G,T174M和G-217A位点多态性对血压的影响。结果:按意向处理分析,263例实验对象均进入结果分析。①血管紧张素原基因A-6G位点AA,AG,GG基因型(P=0.014)以及A,G等位基因频率(P=0.004,OR=0.44)差异明显;T174M位点CC,CT,TT基因型(P=0.031)以及C,T等位基因频率(P=0.014,OR=0.55)差异有显著性意义;未发现G-217A位点GG,AG,AA基因型(P=0.722)以及G,A等位基因频率(P=0.403,OR=0.80)有明显差异。②携带A-6G多态AA基因型和T174M多态CC基因型的个体发生原发性高血压的风险分别减少57%(95%可信区间=0.23～0.82,P=0.010)和56%(95%可信区间=0.25～0.79,P=0.006)。③两组血管紧张素原基因A-6G,T174M和G-217A位点各基因型的收缩压、舒张压和平均动脉压的差异均无显著性意义(F=0.100～2.911,P均>0.05)。结论:血管紧张素原基因A-6G位点AA基因型和T174M位点CC基因型可能会减少中国汉族人群原发性高血压发病风险,未发现G-217A多态基因型与其有显著相关性。     

Cytokine promoter polymorphisms in Taiwanese patients with Graves' disease

OBJECTIVES: This study aimed to examine the association between promoter polymorphisms of Th1 and Th2 cytokine genes [interleukin-4 (IL-4 T-34C, A-81G, C-285T and T-589C), IL-6 (G-174C), IL-10 (A-592C and T-819C) and tumour necrosis factor-alpha (TNF-alpha G-238A and G-308A)] and Graves' disease (GD) in Taiwanese population. DESIGN AND METHODS: Genomic DNA was extracted from peripheral blood cells of 137 GD patients and 189 control subjects. Cytokine gene polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: Genotype frequencies of TNF-alpha G-238A or G-308A between control and GD subjects were significantly different. Frequencies of the high TNF-alpha secreting alleles (-238*A and -308*A) and IL-10 -819*C allele were significantly increased in GD patients. No significant differences regarding IL-4 or IL-6 gene polymorphisms between GD patients and control subjects were found. CONCLUSIONS: Our data demonstrated that TNF-alpha G-238A and G-308A genotypes were strongly associated with GD incidence.     

解偶联蛋白1基因多态性与2型糖尿病心脑血管并发症的相关性

目的 探讨解偶联蛋白1(UCP1)基因多态性与2型糖尿病(T2DM)心脑血管并发症的相关性.方法 选取2019年7月—2020年7月住院治疗的T2DM 440例,根据有无心脑血管并发症分为观察组(T2DM合并心脑血管并发症)221例和对照组(单纯T2DM)219例.比较两组一般资料,UCP1在rs45539933、rs...     

Prevalence of diabetes complications in adolescents with type 2 compared with type 1 diabetes

OBJECTIVE: To compare the prevalence of diabetes complications and their risk factors in youth with type 1 versus type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed a comparative clinic-based study of 1,433 patients with type 1 diabetes and 68 patients with type 2 diabetes aged <18 years from New South Wales, Australia. Retinopathy was assessed by seven-field stereoscopic retinal photography; albumin excretion rate from three consecutive, timed, overnight urine collections; peripheral neuropathy by thermal and vibration threshold; and autonomic neuropathy by pupillometry. HbA(1c) (A1C) and lipids were measured in all patients and C-peptide in patients with type 2 diabetes. RESULTS: In patients with type 1 versus type 2 diabetes, median (interquartile range) age was 15.7 years (13.9-17.0) and 15.3 years (13.6-16.4), respectively (P = 0.2), whereas median diabetes duration was 6.8 years (4.7-9.6) and 1.3 years (0.6-3.1), respectively (P < 0.0001). Retinopathy was significantly more common in patients with type 1 diabetes (20 vs. 4%, P = 0.04), while microalbuminuria and hypertension were significantly less common (6 and 16% in type 1 diabetes vs. 28 and 36% in type 2 diabetes). Rates of peripheral and autonomic neuropathy were similar (27 and 61% in type 1 diabetes vs. 21 and 57% in type 2 diabetes). In multivariate analyses, microalbuminuria was significantly associated with older age (odds ratio 1.3 [95% CI 1.2-1.5], P < 0.001) and systolic hypertension (3.63 [2.0-6.3], P < 0.001) in type 1 diabetes, while only higher A1C (1.7 [1.3-2.9], P = 0.002) was significant in patients with type 2 diabetes. CONCLUSIONS: Youth with type 2 diabetes have significantly higher rates of microalbuminuria and hypertension than their peers with type 1 diabetes, despite shorter diabetes duration and lower A1C. The results of this study support recommendations for early complications screening and aggressive targeting of glycemic control in patients with type 2 diabetes.     

Association of TNF-alpha gene promoter C-857T polymorphism with higher serum LDL cholesterol levels and carotid plaque formation in Japanese patients with type 2 diabetes

Little has been known about the role of tumor necrosis factor-alpha (TNF-alpha) gene polymorphisms in metabolic syndrome and atherosclerosis in type 2 diabetes, although TNF-alpha was reported to be involved in these conditions. We examined the association of TNF-alpha gene promoter polymorphisms, G-238A, G-308A, C-857T, C-863A, and T-1031C, with metabolic syndrome and surrogate markers of atherosclerosis in Japanese patients with type 2 diabetes. DNA was obtained from 162 patients and TNF-alpha gene promoter polymorphisms determined by direct sequencing. Allelic frequency of -238A, -308A, -857T, -863A, and -1031C was 0.6%, 2.2%, 11.1%, 16.7%, and 15.7%, respectively. Association of the gene polymorphisms with a number of variables, because of their high frequency, was analyzed in the latter 3 polymorphisms. There were no significant differences in components of metabolic syndrome and variables affecting atherosclerosis, except in case of serum low-density-lipoprotein cholesterol (LDL-C) (111+/-33 vs 125+/-39 mg/dl, p<0.05) between -857C/C and -857(C/T+T/T). In contrast, no significant differences were found in these markers between -863C/C and -863(C/A+A/A) and between -1031T/T and -1031(T/C+C/C). Furthermore, 87% of the patients with -857(C/T+T/T) and 64% with -857C/C had carotid plaques (p<0.05). There was no difference in proportion of patients treated with medications such as statins, fibrates, oral hypoglycemic agents, insulin, or antihypertensive drugs between -857C/C and -857(C/T+T/T). These data imply that TNF-alpha gene polymorphism (C-857T) is likely associated with higher serum LDL-C levels and carotid plaque formation in Japanese patients with type 2 diabetes.     

云南三民族人群IL-18启动子基因多态性与HBV感染的相关性研究

目的分析云南省西双版纳地区基诺族、傣族和哈尼族人群IL-18启动子基因多态性的分布,并对其多态性与HBV感染的相关性进行探讨。方法运用PCR-测序的方法对三民族人群IL-18启动子G-137C、C-607A和G-656T位点进行基因分型,并分析其基因多态性与HBV感染的相关性。结果 （1）基诺族人群G-137C位点基因型和等位基因分布频率与其他两民族相比差异有统计学意义（基诺族vs.傣族：χ2值分别为49.374和37.482,P值均为0.000;基诺族vs.哈尼族：χ2值分别为34.028和26.900,P值均为0.000）。（2）C-607A（G-656T）位点基因型与等位基因分布频率三民族相比均有统计学意义（基诺族vs.傣族：χ2值分别为21.140和16.681,P值均为0.000;基诺族vs.哈尼族：χ2值分别为8.166和5.061,P值分别为0.017和0.024;傣族vs.哈尼族：χ2值分别为8.115和6.140,P值分别为0.017和0.013）。（3）哈尼族人群HBsAg阳性组与HBsAg阴性组G-137C基因型分布频率差异有统计学意义（χ2=9.776,P=0.008）,CC基因型与GG基因型＋GC基因型相比P=0.026,OR=6.194,95%CI=1.310～29.299;GC基因型与CC基因型＋GG基因型相比P=0.036,OR=0.311,95%CI=0.105～0.924。结论 IL-18启动子G-137C、C-607A和G-656T基因型和等位基因分布频率具有民族差异,其多态性对HBV感染易感性的影响也因民族不同有所差异,G-137C多态性与哈尼族HBsAg携带相关。     

Association among individual deprivation, glycemic control, and diabetes complications: the EPICES score

OBJECTIVE: Previous studies have related poor glycemic control and/or some diabetes complications to low socioeconomic status. Some aspects of socioeconomic status have not been assessed in these studies. In the present study, we used an individual index of deprivation, the Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé (Evaluation of Precarity and Inequalities in Health Examination Centers [EPICES]) score, to determine the relationship among glycemic control, diabetes complications, and individual conditions of deprivation. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional prevalence study in 135 consecutive diabetic patients (age 59.41 +/- 13.2 years [mean +/- SD]) admitted in the hospitalization unit of a French endocrine department. Individual deprivation was assessed by the EPICES score, calculated from 11 socioeconomic questions. Glycemic control, lipid levels, blood pressure, retinopathy, neuropathy, and nephropathy were assessed. RESULTS: HbA(1c) level was significantly correlated with the EPICES score (r = 0.366, P < 0.001). The more deprived patients were more likely than the less deprived patients to have poor glycemic control (beta = 1.984 [SE 0.477], P < 0.001), neuropathy (odds ratio 2.39 [95% CI 1.05-5.43], P = 0.037), retinopathy (3.66 [1.39-9.64], P = 0.009), and being less often admitted for 1-day hospitalization (0.32 [0.14-0.74], P = 0.008). No significant relationship was observed with either nephropathy or cardiovascular risk factors. CONCLUSIONS: Deprivation status is associated with poor metabolic control and more frequent microvascular complications, i.e., retinopathy and neuropathy. The medical and economic burden of deprived patients is high.     

Cardiovascular morbidity and early mortality cluster in parents of type 1 diabetic patients with diabetic nephropathy

OBJECTIVE: A familial predisposition was proposed to be a determinant of the increased morbidity and mortality from cardiovascular disease in type 1 diabetic patients with diabetic nephropathy. The insertion allele of an insertion/deletion polymorphism in the ACE (ACE/ID) gene seems to protect against coronary heart disease in nondiabetic and diabetic subjects. The aim of the present study was to evaluate these hypotheses in parents of a large group of type 1 diabetic patients with and without diabetic nephropathy. RESEARCH DESIGN AND METHODS: We investigated cardiovascular morbidity and mortality of parents of 163 type 1 diabetic patients with nephropathy and parents of 163 sex- and age-matched normoalbuminuric patients with type 1 diabetes. RESULTS: Kaplan-Meier curves showed that total parental mortality was significantly increased in parents of type 1 diabetic patients with nephropathy (121 of 244 [ approximately 50%] ) as compared with parents of normoalbuminuric type 1 diabetic patients (119 of 269 [approximately 44%]) (P = 0.008 [log-rank test]) partially due to an increase in cardiovascular deaths (48 of 244 [approximately 20%] vs. 42 of 269 [approximately 16%], P<0.05). In addition, more patients with nephropathy, as compared with the normoalbuminuric group, had at least one parent with fatal/nonfatal cardiovascular disease (46% [95% CI 38-54] vs. 36% [28-44], P = 0.05). Fathers of patients homozygous for the I-allele of the ACE/ID polymorphism had significantly less myocardial infarction as compared with other genotypes (P = 0.03), regardless of the nephropathic state of the offspring. CONCLUSIONS: Cardiovascular morbidity and early mortality clusters in parents of type 1 diabetic patients with diabetic nephropathy The ACE/ID polymorphism helps explain the increased morbidity from cardiovascular disease.     

维生素D受体基因多态性与2型糖尿病的易感性研究

【目的】探讨维生素D受体基因BsmI、ApaI位点多态性与汉族人群2型糖尿病的相关性。【方法】采用PCR-限制性多态性片断长度（RFLP）技术检测83例健康对照（NC）者、96例2型糖尿病（T2DM）患者的维生素D受体BsmI、ApaI位点基因型和等位基因频率。【结果】①T2DM组与NC组BsmI位点基因型、等位基因频率分布差异有统计学意义（均P〈0．05）,两组间等位基因B的相对风险率为2．50。②T2DM组与Nc组Apal位点基因型、等位基因频率分布差异均无统计学意义（x2=0．344,P=0．842;x2=0．090,P=0．765）。【结论】维生素D受体基因BsmI位点与2型糖尿病的发生密切相关,等位基因B可能是2型糖尿病的易感基因。     

The knack of treatment for obese patients with hypertension and diabetes mellitus: combined the newest tailor-made diet therapy with the usual stress-management therapy

The 5-10% body weight loss often leads to amelioration or cure of hypertension and diabetes mellitus in obese patients. But, the effect of diet therapy on obese patients differs in each individual because of the differences in energy expenditure, such as the resting metabolic rate (RMR). We have recently reported that obese Japanese with the missense mutation (Trp64Arg) of the beta 3-adrenergic receptor (beta 3-AR) gene and/or the uncoupling protein 1 (UCP1) gene mutation (A-3826G) have difficulties in weight loss by the reducing RMR, while Japanese with beta 2-AR gene mutation (Arg16Gly) have an under-weight condition through increased RMR. Here I introduce the importance of tailor-made diet therapy to improve obesity based on analysis of gene polymorphisms and in order to maintain this tailor-made diet therapy, I emphasize that the stress-management therapy should be needed to remove mental problems which caused obesity.     

Cortisol secretion in patients with type 2 diabetes: relationship with chronic complications

OBJECTIVE: The presence of an enhanced cortisol secretion in patients with type 2 diabetes is debated. In type 2 diabetic subjects, cortisol secretion was found to be associated with the complications and metabolic control of diabetes. We evaluated cortisol secretion in 170 type 2 diabetic subjects and in 71 sex-, age-, and BMI-matched nondiabetic subjects. RESEARCH DESIGN AND METHODS: In all subjects, we evaluated ACTH at 8:00 a.m. in basal conditions and serum cortisol levels at 12:00 p.m. (F24) and at 9:00 a.m. after a 1-mg overnight dexamethasone suppression test and 24-h urinary free cortisol (UFC). In diabetic patients, we evaluated the presence of chronic complications (incipient nephropathy, asymptomatic neuropathy, background retinopathy, and silent macroangiopathy). Patients were subdivided according to the absence (group 1, n = 53) or presence (group 2, n = 117) of diabetes complications. RESULTS: In group 2, UFC (125.2 +/- 4.6 nmol/24 h) and F24 (120.6 +/- 4.1 nmol/l) were higher than in group 1 (109.2 +/- 6.8 nmol/24 h, P = 0.057, and 99.7 +/- 6.1 nmol/l, P = 0.005, respectively) and in nondiabetic patients (101.7 +/- 5.9 nmol/24 h, P = 0.002, and 100.3 +/- 5.3 nmol/l, P = 0.003, respectively). In diabetic patients, the number of complications was associated with F24 (R = 0.345; P < 0.0001) and diabetes duration (R = 0.39; P < 0.0001). Logistic regression analysis showed that the presence of diabetes complications was significantly associated with F24, sex, duration of diabetes, and glycated hemoglobin. CONCLUSIONS: In type 2 diabetic subjects, hypothalamic-pituitary-adrenal activity is enhanced in patients with diabetes complications and the degree of cortisol secretion is related to the presence and number of diabetes complications.     

Role for mitochondrial uncoupling protein-2 (UCP2) in hyperhomocysteinemia and venous thrombosis risk?

BACKGROUND: Hyperhomocysteinemia has been associated with an increased risk of venous thrombosis, which might be mediated through an oxidative stress dependent mechanism. The function of uncoupling protein-2 (UCP2) is still under debate, but it has been suggested to play a role in reduction of mitochondrial reactive oxygen species. In the present study, we investigated whether the 45 bp deletion/insertion (del/ ins) polymorphism in the UCP2 gene is associated with elevated homocysteine levels and whether it might be associated with an increased risk of recurrent venous thrombosis (RVT). METHODS: The 45 bp del/ins polymorphism in the UCP2 gene was genotyped by PCR analysis in 161 RVT cases and 386 controls of Caucasian origin in which fasting- and post-load homocysteine levels were previously determined. Statistical analysis was performed to assess whether the UCP2 45 bp del/ins polymorphism was associated with plasma total homocysteine levels and venous thrombosis risk. RESULTS: Post-load homocysteine levels were positively associated with UCP2 45 bp ins/ins genotype (P = 0.02). None of the UCP2 45 bp ins/del genotypes were associated with fasting plasma homocysteine levels. The frequency of the UCP2 45 bp ins/ins genotype was 12.4% in RVT cases compared to 8.3% in controls, which resulted in an odds ratio of 1.8 (95% CI 1.0-3.4). CONCLUSIONS: The results of our study show that the common 45 bp del/ins polymorphism in the UCP2 gene is associated with hyperhomocysteinemia, which might increase the risk of venous thrombosis. However, the mechanism is not fully understood and additional studies should be performed to confirm our findings.