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。     

北京地区人群解偶联蛋白2基因启动子-866G／A变异与2型糖尿病的风险

目的：探讨北京地区人群解偶联蛋白2启动子区域-866G／A位点与2型糖尿病发生的关系。方法：采用多聚酶链反应-限制性内切酶片段长度多态性技术检测北京地区470例2型糖尿病散发患者和217名健康人群中解偶联蛋白2启动子866G／A的分布情况,并将该基因型分布模式与国际人类基因组单倍体型计划数据库中的人群模式进行比较,比较不同基因型间临床指标的差异。结果：未发现解偶联蛋白2—866G／A位点各基因型和等位基因与2型糖尿病的发生存在显著性关联（P=0538,0301）。该基因型分布模式与国际人类基因组单倍体型计划数据库中的日本人群模式更为相近。以性别、腰围和体质量指数为协变量进行了分层分析和Logisitic回归调整,但结果仍未发现该变异位点各基因型和等位基因与2型糖尿病的发生存在显著性关联。比较不同基因型和血压、肥胖指标（体质量指数、腰围、腰臀比）、血糖指标（糖化血红蛋白、空腹血糖、餐后2h血糖）、血脂、胰岛素等临床指标及胰岛素抵抗相关指数的关系,所有基因型间指标比较未发现存在具有临床意义的显著性差异。结论：未发现解偶联蛋白2基因启动子区域-866G／A变异位点的基因型和等位基因分布对2型糖尿病的发生风险存在贡献效应,其可能不是北京人群2型糖尿病发生的易感基因。     

白细胞介素-18基因多态性与肺结核病易感性的关系

目的：通过病例-对照研究,探讨白细胞介素-18（IL-18）基因启动子区-607C/A、-137G/C位点单核苷酸多态性（SNP）与肺结核病的关系。方法：采用序列特异性引物PCR（PCR-SSP）及测序技术检测深圳地区汉族人群肺结核患者200例及健康对照者197例IL-18启动子区-607 C/A 、-137G/C位点多态性基因型。采用直接计数法计算各组基因型频率及等位基因频率,进行χ2 检验。以P值＜0.05为具有统计学意义。结果：肺结核患者IL-18启动子区-607位点A/A纯合子、A/C杂合子、C/C纯合子基因型频率分别为19.5%、55.0%、25.5% ;A、C等位基因频率分别为47.0%、53.0%。健康对照者A/A纯合子、A/C杂合子、C/C纯合子基因型频率分别为22.8%、46.7%、30.5%;A、C等位基因频率分别为46.2%、53.8%。两组人群-607位点基因型及等位基因分布无明显差异(P>0.05)。肺结核患者IL-18启动子区-137G/C位点C/C纯合子、C/G杂合子、G/G纯合子基因型频率分别为4.5%、18.5%、77.0%;C、G等位基因频率分别为13.8%、86.2%。健康对照者C/C纯合子、C/G杂合子、G/G纯合子基因型频率分别为5.6%、25.9%、68.5%;C、G等位基因频率分别为18.5%、81.5%。两组人群-137位点基因型分布无明显差异(P>0.05)。结论：IL-18启动子区-607、-137位点基因多态性与中国汉族人群肺结核病易感性无关。     

成纤维细胞生长因子1基因启动子多态性与晚发型阿尔茨海默病的相关性研究

目的探讨成纤维细胞生长因子1（FGF-1）基因启动子多态性是否与晚发型阿尔茨海默病（LOAD）相关.方法收集206例尸体检查的样本,包括100例LOAD和年龄匹配的对照组106例.PCR-RFLP（Restriction fragment length polymorphism）法分析FGF-1基因启动子（-1385 A/G）的基因型.结果FGF-1基因启动子（-1385 A/G）的基因型频率分布是：AA型20例（10%）,GA型89例（43%）,GG型97例（47%）,在LOAD组和对照组之间,不同基因型频率分布有显著性差异（P=0.027）;GG基因型与LOAD呈正相关（odds ratio-2.02,95%CI：1.16～3.52）.结论FGF-1基因启动子（-1385 A/G）多态性与LOAD显著相关.     

多巴胺D1受体-48 A/G基因多态性与脑出血的相关性研究

目的：探讨多巴胺D1受体基因-48 A/G[DRD1（-48 A/G）]多态性与中国湖南地区汉族人群脑出血发病的相关性。方法：筛选121例脑出血患者及115例年龄、性别相匹配的正常体检人群,应用聚合酶链式反应（PCR）-限制性片段长度多态性（RFLP）方法测定DRD1（-48 A/G）基因的多态性。结果：在中国湖南汉族人群中,DRD1（-48 A/G）基因型分布为AA 63.2%,AG 31.3%和GG 5.5%,等位基因A和G频率分别为78.9%和21.1%。DRD1（-48 A/G）三种基因型频率及两种等位基因频率在脑出血组和正常对照组分布差异无显著性（P〉0.05）。脑出血组中高血压和非高血压两亚组间DRD1（-48 A/G）基因型频率分布差异无显著性（P〉0.05）,且它们分别和对照组比较DRD1（-48A/G）基因型频率分布差异无显著性（P〉0.05）。Log istic回归调整了脑出血环境因素的影响后,DRD1（-48 A/G）基因多态性与脑出血的关系仍无统计学意义（P〉0.05）。结论：DRD1（-48 A/G）基因多态性可能与中国湖南地区汉族人群脑出血无关。     

云南汉族人群Tim-1基因多态性与系统性红斑狼疮关联性研究

目的探讨Tim-1启动子区-416G〉C和-1454G〉A位点基因多态性与云南高原地区汉族人群系统性红斑狼疮（SLE）的遗传易感性有无关联。方法采用PCR-RFLP方法对132名云南汉族SLE病人和120名健康体检者Tim-1启动子区多态性位点-416G〉C和-1454G〉A的基因多态性进行检测,同时采用间接免疫荧光法检测其抗双链DNA抗体、抗Sm抗体、抗RNP抗体三种自身抗体。结果 SLE组和对照组Tim-1启动子区多态性位点-416G〉C的基因型及等位基因频率差异均无统计学意义（P〉0.05）,而-1454G〉A位点的基因型及等位基因频率在SLE组与对照组中的差异均有统计学意义（P〈0.05）;SLE组和对照组三种SLE相关自身抗体检测阳性率差异有统计学意义（P〈0.05）;SLE组两个位点不同基因型中三种自身抗体检测阳性率的差异均无统计学意义（P〉0.05）。结论云南汉族人群Tim-1启动子区-416G〉C和-1454G〉A位点存在单核苷酸多态性变异,且-1454G〉A位点多态性变异与SLE遗传易感性相关,但两位点不同基因型不会影响SLE相关自身抗体的表达。     

中国人群脂联素基因启动子区-11377C/G位点多态性与2型糖尿病易感性的Meta 分析

目的 探讨中国人群脂联素基因启动子区-11377C/G位点多态性与2型糖尿病易感的相关性.方法 检索2011年11月前中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)、万方数据库、维普中文科技期刊数据库(VIP)及Medline、Cochrane Library、Embase、Springer、Ovid等数据库,收集有关中国人群脂联素基因-11377C/G多态性与2型糖尿病的相关性研究;评价纳入研究质量,提取有效数据,采用Review Manager5.0软件进行Meta分析.结果 共纳入12组研究中国人群脂联素基因启动子区-11377C/G位点多态性与2型糖尿病的相关性的病例-对照研究,2型糖尿病病例2 598例,对照4 508例.Meta分析发现,脂联素基因启动子区-11377C/G位点C/G多态性与2型糖尿病相关性中G等位基因与C等位基因[OR=1.14,95%CI(1.03,1.25),P=0.009]、基因型(CG+GG)与CC[OR=1.19,95%CI(1.06,1.35),P=0.004]、基因型CG与CC[OR=1.14,95%CI(1.00,1.29),P=0.05]、基因型GG与CC[OR=1.34,95%CI(1.06,1.71),P=0.02]均具有统计学意义差异.结论 中国人群脂联素基因启动子区-11377C/G位点多态性与2型糖尿病易感性存在相关性.     

我国广东地区汉族人群类风湿性关节炎患者 IL-6启动子基因多态性的研究

目的了解我国广东地区汉族人群白细胞介素-6（IL-6）基因启动子-572C/G和-174G/C位点单核苷酸多态性对类风湿性关节炎（RA）的影响。方法应用序列特异性引物-聚合酶链反应（PCR-SSP）检测168名体检健康者和120例RA患者的IL-6基因启动子-572和-174位点的基因型。结果我国广东地区汉族人群IL-6基因启动子-572位点存在C→G的突变,其基因型和等位基因频率分布在RA组和对照组比较差异有统计学意义（基因型频率：2χ=16.14,P=0.003;等位基因频率：2χ=16.71,P〈0.001）,其G等位基因在RA患者中明显低于健康对照组[比值比（OR）=0.36,95%可信区间（CI）：0.21-0.61];-174位点存在G→C的突变,其基因型和等位基因分布频率在两组间差异亦有统计学意义（基因型频率：2χ=25.75,P〈0.01;等位基因频率：2χ=25.99,P〈0.01）,其C等位基因在RA组明显高于健康对照组（OR=2.26,95%CI：1.91-2.68）。结论我国广东地区汉族人群IL-6基因启动子存在-572C/G与-174G/C的单核苷酸多态性,且这2个位点多态性与RA有关,其中IL-6-572位点的G等位基因可能对RA有保护作用,而IL-6-174位点等位基因C可能与RA发病的易感性有关。     

肥胖儿童瘦素受体基因变异对脂质代谢及脂肪分布的影响

目的探讨瘦素受体（leptin receptor,LEPR）基因第20外显子变异对脂质代谢的影响。方法用聚合酶链式反应-限制性片断长度多态性（PCR-RFLP）法及聚丙烯酰胺凝胶电泳法分析120例单纯型肥胖儿童及120例健康儿童的LEPR基因的第20外显子基因变异频率,并测定血清中甘油三脂（TG）、总胆固醇（TC）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）,于相同条件下测身高、体重,按公式计算体重指数（BMI）、脂肪百分比（?t）。结果共检出3种第20外显子的基因型,其酶切片段分别为：A/A型：201bp,75bp;A/G型：201bp,173bp,75bp,28bp;G/G型：173bp,75bp,28bp。肥胖儿童较健康儿童LEPR基因第3057位G→A突变频率增高（P〈0.05）。纯合子A/A基因型的肥胖儿童其血清TG浓度、BMI、?t均明显高于纯合子G/G基因型者（P〈0.01）,而血清HDL水平则明显低于后者（P〈0.01）,杂合子A/G型肥胖儿童,除其血清TG浓度高于纯合子G/G基因型者外（P〈0.05）,余各项指标均与另外两种基因型无显著性差异。结论单纯型肥胖儿童瘦素受体基因第20外显子存在基因多态性的变化,且这种变化明显影响肥胖儿童的脂质代谢及体脂分布。纯合子A/A基因型个体应提早注意饮食结构,避免由此而继发的各种疾病。     

醛糖还原酶基因启动子区C（-106）T多态性与2型糖尿病视网膜病的相关性

目的 探讨醛糖还原酶（ALR）基因启动子区C（-106）T多态性在甘肃地区回族人群中的分布及其与糖尿病视网膜病的关系.方法 应用PCR-RFLP技术检测67例2型糖尿病患者和70例健康对照者ALR的基因型,分别以氧化酶法、放免法、比色法测定空腹血糖、空腹胰岛素、糖化血红蛋白水平.结果 ALR基因C（-106）T多态各基因型及等位基因分布频率在对照组和2型糖尿病组间差异无统计学意义;糖尿病视网膜病组T等位基因分布频率明显高于无糖尿病视网膜病组,等位基因相对危险度分析发现,携带T等位基因的2型糖尿病患者发生糖尿病视网膜病的风险是C等位基因的2.262倍.结论 在甘肃地区回族人群中存在ALR基因启动子区C（-106）T多态性,且T等位基因可能与糖尿病视网膜病的发生相关.     

Simple and rapid detection of uncoupling protein-2 - 866G/A polymorphism by mutagenically separated polymerase chain reaction

BACKGROUND: Uncoupling protein-2 (UCP2), a recently identified member of the mitochondrial transporter superfamily, is a candidate gene for obesity. A common G/A polymorphism in the UCP2 promoter region is associated with enhanced adipose tissue mRNA expression in vivo. METHODS: We developed a rapid and simple method, mutagenically separated polymerase chain reaction (MS-PCR) for genotyping UCP2 - 866G/A polymorphism. Two reverse mutagenic allele-specific primers of different lengths for the UCP2 - 866G/A polymorphic site were paired with the same forward primer in the same PCR reaction. RESULTS: Agarose gel electrophoresis (3.5%) showed at least one of the two allelic products and provided a within-assay quality control to exclude false-negative results. The 203-bp fragment of the PCR products was A allele-specific and the 183-bp fragment was G allele-specific. The frequencies of the UCP2 - 866G/A genotypes in 72 Japanese subjects were AA: 21 (29.2%), AG: 32 (44.4%), and GG: 19 (26.4%). The results were confirmed by the PCR-RFLP genotyping method, in which a 360-bp fragment of PCR products was cut into 290- and 70-bp fragments by the restriction enzyme MluI when the G allele was present. This Japanese group showed a higher frequency of the AA genotype, which is associated with a low prevalence of obesity, than Caucasian populations. CONCLUSIONS: The MS-PCR technique is a simple, rapid, and reliable method for genotyping UCP2 - 866G/A polymorphism.     

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.     

Analysis of candidate genes in Polish families with obesity.

This study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), tumor necrosis factor-alpha (TNF-alpha)); iii) thermogenesis and free fatty acid (FFA) transport/catabolism (uncoupling protein-1 (UCP1), lipoprotein lipase (LPL), beta2- and beta3-adrenergic receptor (beta2AR, beta3AR), fatty acid transport protein-1 (FATP-1) and iv) lipoproteins (apoliprotein E (apoE), apo CIII). The 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated. The single gene mutations such as C105 T OB and Pro115 Gln PPAR-gamma2 linked to morbid obesity were not detected in our group. A weak correlation between obesity and certain gene polymorphisms was observed. Being overweight (25 < BMI > or = 30 kg/m2) significantly correlated with worse FFA tolerance in male PPAR-gamma2 12Pro, LPL-H (G) allele carriers. Insulin resistance was found in female PPAR-gamma2 Pro12, TNF-alpha (-308A) and LPL-H (G) allele carriers. Hypertension linked to the PPAR-gamma2 Pro allele carriers was characterized by high leptin output during OLTT. We conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.     

Functional polymorphisms of UCP2 and UCP3 are associated with a reduced prevalence of diabetic neuropathy in patients with type 1 diabetes

OBJECTIVE: We studied the association between polymorphisms in the UCP genes and diabetes complications in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: We analyzed 227 patients with type 1 diabetes using PCR and subsequent cleavage by restriction endonucleases for the promoter variants A-3826G in the UCP1 gene, G-866A in the UCP2 gene, and C-55T in the UCP3 gene. RESULTS: No effect of the A-3826G polymorphism in the UCP1 gene on diabetes complications was found. Patients who were heterozygous or homozygous for the G-866A polymorphism in the UCP2 gene or the C-55T polymorphism in the UCP3 gene had a significantly reduced prevalence of diabetic neuropathy (UCP2: odds ratio 0.44 [95% CI 0.24-0.79], P = 0.007; UCP3: 0.48 [0.25-0.92], P = 0.031), whereas there was no association with other diabetes complications. This effect was stronger when G-866A and C-55T occurred in a cosegregatory manner (UCP2 and UCP3: 0.28 [0.12-0.65], P = 0.002). Furthermore, a multiple logistic regression model showed an age- and diabetes duration-independent effect of the cosegregated polymorphisms on the prevalence of diabetic neuropathy (P = 0.013). CONCLUSIONS: Our data indicate that both the G-866A polymorphism in the UCP2 gene and the C-55T polymorphism in the UCP3 gene are associated with a reduced risk of diabetic neuropathy in type 1 diabetes. Thus, the results presented here support the hypothesis that higher expression of uncoupling protein might prevent mitochondria-mediated neuronal injury and, ultimately, diabetic neuropathy.     

Peroxisome proliferator-activated receptor gamma gene polymorphism is associated with serum triglyceride levels and body mass index in Japanese type 2 diabetic patients

Peroxisome proliferator-activated receptor gamma (PPARgamma) controls adipocyte differentiation and regulates lipid and glucose homeostasis. Therefore, the PPARgamma gene may affect insulin sensitivity and resistance. We analyzed the relationship between C/T exon 6 polymorphism of the PPARgamma gene and various clinical parameters in type 2 diabetic patients. There were no significant differences in the frequencies of genotype and allele between diabetic patients with and without nephropathy. Diabetic patients were divided into two groups: patients bearing at least one T allele (CT/TT), and patients with no T allele (CC). Levels of serum triglyceride and body mass index (BMI) were significantly higher in the CT/TT genotype group than in the CC genotype group. Since obesity affects insulin resistance, the diabetic patients were also divided into two groups: those with a BMI of <23, and those with a BMI of >23. In patients with a BMI of <23, there was no significant change in the levels of glycosylated hemoglobin A1c (HbA1c) between the CC and CT/TT genotype groups. However, in patients with a BMI of >23, HbA1c levels were significantly higher in the CT/TT genotype group than in the CC genotype group. It appears that the CT/TT genotype with PPARgamma gene polymorphism may contribute to higher BMI and higher serum triglyceride and HbA1c levels in Japanese type 2 diabetic patients.     

Obesity,Type II diabetes and the beta 2 adrenoceptor gene Gln27Glu polymorphism in the Tongan population

As there is a high prevalence of obesity in Tonga, we aimed to determine the distribution of the beta2 adrenoceptor gene Gln(27)Glu polymorphism and to assess its relevance to obesity and to Type II diabetes, known to be prevalent in that population. A random sample of 1022 individuals from Tonga were genotyped for the Gln(27)Glu polymorphism in the beta 2 adrenoceptor gene. To assess the prevalence of obesity we measured body-mass index (BMI), fat-free mass, percentage fat and waist-to-hip ratio (WHR). To assess glucose metabolism we measured HbA(1c), fasting blood glucose, fasting serum insulin, and 1- and 2-h glucose; we also measured serum lipid and creatinine levels. We found that 84% of the Tongan men and 93% of the women were overweight or obese (BMI > or = 25 kg/m(2)) and 15.1% had Type II diabetes. Genotype frequencies among the 1022 Tongans were: Gln/Gln 90.3% and Gln/Glu 9.6%; we found one Glu/Glu homozygote. The mean BMI (+/-S.D.) for men was not significantly different for those who were homozygous (30.2+/-5.4 kg/m(2)) or heterozygous (30.1+/-5.5 kg/m(2)) for the Gln allele; this was also true for women (33.7+/-6.2 kg/m(2) for homozygous and 34.0+/-5.6 kg/m(2) for heterozygous). The Glu allele was not associated with other measures of obesity or abnormal glucose metabolism in this generally overweight population. There is a unique frequency of the Gln/Glu beta 2 adrenoceptor polymorphism among Tongans. We found no association of the polymorphism with obesity measures or Type II diabetes-related variables in the Tongan population among whom we documented a high prevalence of obesity and Type II diabetes and a low frequency of the Glu allele.     

瘦素受体基因Pro1019Pro变异与单纯性肥胖的关系

目的　探讨瘦素受体基因第 2 0号外显子 30 5 7位Pro10 19Pro基因变异与儿童单纯性肥胖之间的关系。方法　应用聚合酶链反应—限制性酶切片断长度多态性 (PCR -RFLP)方法测定瘦素受体基因Pro10 19Pro的基因变异频率 ,同时测血脂、身高、体重。结果　瘦素受体基因Pro10 19Pro(G→A)基因变异频率在肥胖组与正常对照组间差异无显著意义 (P >0 .0 5 )。血脂水平与体重指数 (BMI)在肥胖组与正常对照组间差异有显著意义 (P <0 .0 5 ) ;肥胖组中及正常对照组中GG基因型与AA基因型间BMI值与血脂水平均差异无显著意义 (P >0 .0 5 )。结论　瘦素受体基因第 2 0号外显子 30 5 7位Pro10 19Pro变异在儿童单纯性肥胖的发病机制中无重要作用 ,血脂水平及体重指数不受该基因变异的影响     

Insulin action in black Americans with NIDDM.

OBJECTIVE--To assess the influences that obesity and hyperglycemia have on insulin action in black NIDDM patients. RESEARCH DESIGN AND METHODS--Thirty-nine subjects were studied who had normal GHb levels and/or FPG less than 6.4 mM and who had not taken pharmacological agents for 2-91 mo before the study. Insulin action was studied using the euglycemic insulin clamp with a D-[3-3H]glucose infusion. Degree of obesity was assessed with BMI. During carefully monitored follow-up, 9 patients relapsed into a hyperglycemic state, and insulin action was restudied after acute reregulation of their plasma glucose. RESULTS--Insulin action was related to the degree of obesity at the extremes of BMI: 7 of 8 patients (87.5%) with a BMI less than 24.0 kg/m2 were insulin sensitive, and 8 of 9 patients (88.9%) with a BMI greater than 28.5 kg/m2 were insulin resistant. In the midrange BMI (24.0-28.5 kg/m2), patients were equally likely to be insulin resistant or insulin sensitive. A plot of frequency versus glucose disposal in those patients was compatible with a bimodal distribution (P less than 0.025): 12 of 22 patients were normally insulin sensitive (glucose disposal 6.1-9.4 mg.kg-1.min-1), and 10 were insulin resistant (glucose disposal 2.4-4.8 mg.kg-1.min-1). Analysis of this midrange BMI group showed that in the insulin-sensitive group, an inverse relationship existed between BMI and glucose disposal (r = -0.64, P less than 0.05), whereas no such relationship was found in the insulin-resistant group. The clinical characteristics of the midrange BMI group indicated that fasting plasma insulin, total cholesterol, and triglycerides were higher; whereas BMI, age, and FPG were not different in the insulin-resistant compared with the insulin-sensitive group. With the development of hyperglycemia, insulin action in the insulin-sensitive group. With the development of hyperglycemia, insulin action in the insulin-sensitive group was decreased, independent of obesity, whereas it was unchanged in the insulin-resistant group. CONCLUSIONS--Insulin resistance exists in only approximately 50% of black NIDDM patients. The relationship between obesity and insulin resistance is not a simple one. The data can be explained by one of two hypotheses: 1) insulin resistance in black NIDDM patients is an acquired defect related to the development of obesity and is modulated by hyperglycemia, or 2) NIDDM exists as two variants, one with primary insulin resistance and one with normal insulin sensitivity, and that insulin resistance causes central and/or generalized obesity.     

Diabetes, hyperinsulinemia, and hyperlipidemia in small aboriginal community in northern Australia

A small rural Aboriginal community in northern Australia was surveyed for diabetes, impaired glucose tolerance (IGT), hyperinsulinemia, and lipid levels. Of the 122 adults greater than 17 yr of age who participated (95% response rate), 11.5% had diabetes, 7.4% had IGT, and the remaining 81.1% had normal glucose tolerance. Both diabetes and IGT were strongly age related. This high frequency of diabetes occurred, despite the population being relatively lean. Although the body mass index (BMI) increased with age in both men and women, only 25% of the population overall had BMI greater than 25 kg/m2. There were wide ranges of insulin responses to glucose, with the upper tertile of 2-h insulin levels being more than seven times higher than the lower tertile (144 +/- 13 vs. 19 +/- 1 mU/L). Hyperinsulinemia was associated with IGT, elevated triglycerides, and lower high-density lipoprotein cholesterol levels. Lipid abnormalities were much more frequent among men than women. Cholesterol levels were an average of 0.55 mM higher and triglycerides an average of 1.05 mM higher in men than in women, and both increased with age. In conclusion, this small isolated Aboriginal population from northern Australia had an unexpectedly high frequency of diabetes (in view of their relative leanness) in association with a high frequency of metabolic abnormalities indicative of insulin resistance (hyperinsulinemia, IGT, hypertriglyceridemia).