A common mitochondrial DNA variant and increased body mass index as associated factors for development of type 2 diabetes: Additive effects of genetic and environmental factors

OBJECTIVE: The suggested correlation between a T-to-C transition at the nucleotide 16189 in mitochondrial DNA (mtDNA) with increasing insulin resistance and adult-onset diabetes mellitus (DM) is debatable. METHODS: Our study examined mtDNA from 462 subjects with type 2 diabetes (T2DM) and 592 normoglycemic controls (non-DM). Each participant's body mass index (BMI), fasting plasma glucose, fasting insulin concentration, insulin resistance index, and beta-cell function were measured. Sequencing for mtDNA, focusing on exploration of the hypervariable polycytosine tract within the control region, was also conducted in all subjects. RESULTS: Prevalence of the mtDNA 16189 variant was significantly different between DM and non-DM subjects (39.2% vs. 30.7% respectively; P = 0.004). Increased incidence of DM was noted in those harboring the 16189 variant compared with those lacking the variant (multivariate odds ratio, 1.38; 95% confidence interval, 1.07-1.80). Moreover, increased BMI was identified as an aggravating factor for development of DM in subjects harboring the variant. Odds ratio determinations yielded 2.14 in overweight and 4.63 in obese subjects harboring the variant in comparison with subjects without (1.83 in overweight and 2.16 in obese subjects). This is consistent with a progressively increased prevalence of the mtDNA 16189 variant in the non-DM groups with higher fasting insulin concentration, insulin resistance index, and beta-cell function (all P(trend) < 0.005). CONCLUSION: The mtDNA 16189 variant can influence development of T2DM. The demonstrated dynamic between the 16189 variant and increased BMI exemplify an additive effect of genetic and environmental factors on the pathogenesis of T2DM.     

Impact of cardiac rehabilitation on coronary risk factors, inflammation, and the metabolic syndrome in obese coronary patients

Obesity is a coronary heart disease (CHD) risk factor and is prevalent in patients with CHD. The authors reviewed data in 235 consecutive patients before and after formal cardiac rehabilitation and exercise training (CRET) programs and analyzed data in 72 lean patients (body mass index [BMI] <25 kg/m(2)) vs 73 obese patients (BMI>or=30 kg/m(2)). At baseline, obese patients were significantly younger (P<.0001); had higher percentage of body fat (P<.0001) and more dyslipidemia, including higher triglycerides (TG; P<.01), lower high-density lipoprotein (HDL) cholesterol (P<.0001), and higher TG/HDL ratio (P<.0001); and had higher prevalence of metabolic syndrome (61% vs 26%; P<.01) compared with lean patients. Following CRET, obese patients had small, but statistically significant, improvements in obesity indices, including weight (P<.01), BMI (P<.01), and percentage of fat (P=.03), and had more significant improvements in peak exercise capacity (P<.001), HDL cholesterol (P<.001), C-reactive protein (P<.01), behavioral characteristics, and quality of life (P<.0001). The prevalence of metabolic syndrome fell (62% to 51%; P=.1). These results support the benefits of CRET to reduce overall risk in obese patients with CHD.     

The metabolic syndrome in type 1 diabetes: does it exist and does it matter?

The significance of the metabolic syndrome in type 1 diabetes is not well understood. This study aimed to estimate its prevalence and attendant complications. Four hundred twenty-seven type 1 diabetic subjects were grouped according to the presence or absence of metabolic syndrome (WHO criteria). Macro- and microvascular complications were compared between the groups as individual and as composite endpoints. Data were analyzed for the total cohort and in subgroups according to duration of diabetes quartiles (<6.9, 7-12.9, 13-19.9, and >20 years) and year of presentation. Fifteen percent of individuals fulfilled the WHO criteria for metabolic syndrome, and of these, 26.9% were insulin resistant, as compared with 3.4% of those without metabolic syndrome [odds ratio (OR)=8.9, P=.001]. Both BMI and metabolic syndrome showed an increasing trend from 1992 to 2003. Those with metabolic syndrome required significantly higher insulin dosage [0.9 (0.7-1.2) vs. 0.6 (0.5-0.9) units/kg, P=.03], were older [35.0 (26.2-47.3) vs. 29.7 (23.4-36.4) years, P=.002], and had longer duration of diabetes [19.7 (10.7-25.6) vs. 12.1 (6.3-17.9) years, P=.0001]. They also had a significantly higher macrovascular composite endpoint (OR=3.3, P=.02) as well as higher macrovascular and microvascular composite endpoint (OR=3.1, P=.0001). The prevalence of stroke (OR=22.8, P=.008), peripheral vascular disease (OR=7.3, P=.05), and severe retinopathy (OR=3.7, P=.01) is higher in subjects with metabolic syndrome in the >or=20-year quartile group; in addition, these subjects have higher macrovascular composite endpoint (OR=3.9, P=.03) and macrovascular and microvascular composite endpoint (OR=2.9, P=.03). This remained so even when subjects with albuminuria were excluded. Some individuals with type 1 diabetes can also have metabolic syndrome. They are more prone to complications and require even more intensive glycemic control and reduction of macrovascular risk factors.     

Heterogeneous phenotypes of insulin resistance and its implications for defining metabolic syndrome in Asian Indian adolescents

OBJECTIVE: To assess the phenotypic correlations of insulin resistance with obesity and its relationship with the metabolic syndrome in Asian Indian adolescents. DESIGN AND SUBJECTS: We analyzed clinical, anthropometric (body mass index [BMI], waist circumference [WC]) and laboratory (fasting blood glucose [FBG], lipids and fasting serum insulin) data from 793 subjects (401 males and 392 females) aged 14-19 years randomly selected from Epidemiological Study of Adolescents and Young (ESAY) adults (n=1447). The percentile cut-offs for 14-19 years age from ESAY cohort were used for defining abnormal values of variables. We devised three sets of definitions of metabolic syndrome by including BMI and fasting insulin levels with other defining variables. RESULTS: Nearly 28.9% of adolescents had fasting hyperinsulinemia despite normal values of BMI, WC, FBG, lipids, and blood pressure. Remarkably, NCEP criteria with appropriate percentile cut-off points for Asian Indian adolescents identified metabolic syndrome in only six (0.8%) subjects. Inclusion of both BMI and WC in the definition resulted in increase in the prevalence of metabolic syndrome to 4.3%. With inclusion of hyperinsulinemia, the prevalence of metabolic syndrome increased to 4.2% (from 0.8%) in the modified NCEP definition, 5.2% (from 0.9%) when BMI was substituted for WC, and 10.2 (from 4.3%) when both BMI and WC were included. CONCLUSIONS: Our data show marked heterogeneity of phenotypes of insulin resistance and poor value of NCEP definition to identify metabolic syndrome. We propose that BMI and fasting insulin should be evaluated in candidate definitions of metabolic syndrome in Asian Indian adolescents.     

Lipodystrophy and metabolic syndrome in HIV-infected patients treated with antiretroviral therapy

Lipodystrophy (lipo) and metabolic derangements associated with an increased cardiovascular risk are observed frequently in human immunodeficiency virus (HIV)-infected patients who receive antiretroviral treatment (ART). The objective of the study was to provide detailed biochemical information about metabolic syndrome in this condition. One hundred forty-six HIV-infected male and female patients on ART for more than 6 months were compared with 156 body mass index (BMI)-matched healthy subjects. Lipodystrophy was diagnosed upon patient and physician concordance. Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. Plasma adiponectin (AD) and leptin were measured by radioimmunoassay. Insulin resistance (IR) was assessed by the homeostasis model assessment (HOMA). The prevalence of metabolic syndrome was higher in HIV-infected patients on ART than in non-HIV-infected healthy controls (15.8% vs 3.2%; P < .001). Patients with metabolic syndrome are older (44.6 +/- 6 vs 39.8 +/- 8 years; P = .004), have an increased BMI (24.9 +/- 3.8 vs 22.9 +/- 9.8 kg/m(2); P = .01), present with a reduced AD-to-leptin ratio log(10) (-0.19 +/- 0.4 vs 0.5 +/- 0.4; P = .04), and show increased IR (HOMA, 5.6 +/- 2.7 vs 3.8 +/- 2.2; P = .001; plasma fasting insulin, 22.9 +/- 9.8 vs 16.6 +/- 9.7 ng/mL; P < .001). In multivariate analysis, the diagnosis of lipo and HOMA were independently and significantly related to metabolic syndrome. In conclusion, the prevalence of metabolic syndrome is significantly increased in HIV-infected patients on ART and its presence is associated with lipo, increased age and BMI, IR, and a reduced plasma AD-to-leptin ratio.     

Variation of mitochondrial gene and the association with type 2 diabetes mellitus in a Chinese population

Mitochondrial DNA (mtDNA) variants have been implicated in many diseases including diabetes mellitus. To explore whether these genetic variants contribute to the susceptibility for type 2 diabetes mellitus (T2DM) in a Chinese population, a total of 184 T2DM cases and 279 matched healthy controls were recruited. PCR restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing were used to determine the variants of mtDNA (including T16189C, G3316A, T3394C, A14693G, A3243G and C1310T). Some of them were further analyzed by mfold or tRNA-scan-SE software. A homoplastic A14693G, for the first time, was found in 4 of 184 Chinese cases, the frequency of A14693G and T3394C was 2.17% and 2.72%, respectively, in patients but not in the controls. Secondary structure prediction revealed that there were obvious conformational changes in T3394C mutant ND1 versus wild type and A14693G mutant tRNA(Glu) protein versus wild type, providing additional clues to the disease pathogenesis although A3243G and C1310T mutations were not detected in any patients in the two groups. The 16189 variant among type 2 diabetes was more prevalent than in controls (36.9% versus 28.7%, P=0.039), and stepwise multiple regression analysis showed that the 16189 variant was an independent factor contributing to HOMA-IR (R(2)=0.043, P=0.037). Our results suggest that the mutations of T3394C and A14693G may contribute to genetic predisposition to T2DM, with the T16189C variant being associated with insulin resistance.     

Carotid intimal medial thickness in human immunodeficiency virus-infected women: effects of protease inhibitor use, cardiac risk factors, and the metabolic syndrome

CONTEXT: Little is known regarding carotid intimal medial thickness (IMT) in HIV-infected women and the risk factors for subclinical atherosclerosis in this population, including antiretroviral therapy and the metabolic syndrome. OBJECTIVE: Our objective was to assess carotid IMT in relationship to HIV status and antiretroviral therapy in HIV-infected women in comparison with healthy age- and body mass index (BMI)-matched control subjects. SETTING AND SUBJECTS: The study took place at an academic medical center and included 97 HIV-infected women compared with 86 age- and BMI-matched healthy control subjects. MAIN OUTCOME MEASURES: We assessed carotid IMT, metabolic syndrome, and risk factors for increased IMT. Results: Carotid IMT was not increased in HIV-infected women [0.62 mm (0.57-0.68); median (IQR)] compared with non-HIV-infected women [0.61 mm (0.55-0.68)] matched for age and BMI (P = 0.07) but was increased significantly among HIV patients receiving a protease inhibitor (PI) [0.65 (0.59-0.71) mm] vs. non-PI-treated patients [0.61 (0.57-0.66) mm] (P < 0.05) and vs. control subjects [0.61 (0.55-0.68) mm] (P < 0.05). The prevalence of metabolic syndrome was significantly increased among the HIV-infected women compared with control subjects and particularly in PI- vs. non-PI-treated HIV patients (45 vs. 19%, P = 0.001). Metabolic syndrome score correlated with IMT among non-HIV patients but not among the HIV group. Individual risk factors most strongly associated with IMT in multivariate regression modeling in the control group were age and waist-to-hip ratio, and among the HIV group age and waist circumference. CONCLUSIONS: These data demonstrate increased carotid IMT in HIV-infected women receiving PI therapy, which may be due to associated metabolic abnormalities related to PI therapy or more direct effects of this medication class on the vasculature. Additional studies of the mechanisms by which PI uses results in subclinical atherosclerosis are needed.     

The prevalence of the mitochondrial DNA 16189 variant in non-diabetic Korean adults and its association with higher fasting glucose and body mass index.

AIMS: To evaluate the prevalence of the 16189 variant of mitochondrial DNA in Korean adults and its association with insulin resistance. METHODS: We investigated 160 non-diabetic subjects from a community-based diabetes survey conducted in Yonchon County, Korea in 1993. We extracted the DNA from peripheral blood and examined the 16189 variant by polymerase chain reaction and restrictive enzyme digestion. We compared body mass index (BMI), blood pressure, fasting plasma glucose, 2-h plasma glucose after 75 g glucose load, fasting insulin, cholesterol, and homeostasis model assessment of insulin resistance and beta-cell function between the subjects with 16189 variant and wild type. RESULTS: The prevalence of the 16189 variant in Korean adults was 28.8% (46 of 160). Subjects with the 16189 variant had higher fasting glucose and BMI than those with wild type, but fasting insulin, homeostasis model assessment of insulin resistance and beta-cell function, cholesterol, and blood pressure were not different between two groups. CONCLUSION: Our results provide evidence for an association of a frequent mitochondrial polymorphism with higher fasting glucose and the risk factors of diabetes mellitus.     

A mitochondrial DNA variant at position 16189 is associated with type 2 diabetes mellitus in Asians

Aims/hypothesis This multinational study was conducted to investigate the association between a mitochondrial DNA (mtDNA) T16189C polymorphism and type 2 diabetes in Asians. The mtDNA 16189C variant has been reported to be associated with insulin resistance and type 2 diabetes. However, a recent meta-analysis concluded that it is negatively associated with type 2 diabetes in Europids. Since the phenotype of an mtDNA mutant may be influenced by environmental factors and ethnic differences in the nuclear and mitochondrial genomes, we investigated the association between the 16189C variant and type 2 diabetes in Asians. Methods The presence of the mtDNA 16189C variant was determined in 2,469 patients with type 2 diabetes and 1,205 non-diabetic individuals from Korea, Japan, Taiwan, Hong Kong and China. An additional meta-analysis including previously published Asian studies was performed. Since mtDNA nucleotide position 16189 is very close to the mtDNA origin of replication, we performed DNA-linked affinity chromatography and reverse-phase liquid chromatography/tandem mass spectrometry and chromatin immunoprecipitation to identify protein bound to the 16189 region. Results Analysis of participants from five Asian countries confirmed the association between the 16189C variant and type 2 diabetes [odds ratio (OR) 1.256, 95% CI 1.08–1.46, p = 0.003]. Inclusion of data from three previously published Asian studies (type 2 diabetes n = 3,283, controls n = 2,176) in a meta-analysis showed similar results (OR 1.335, 95% CI 1.18–1.51, p = 0.000003). Mitochondrial single-stranded DNA-binding protein (mtSSB) was identified as a candidate protein bound to the 16189 region. Chromatin immunoprecipitation in cybrid cells showed that mtSSB has a lower binding affinity for the 16189C variant than the wild-type sequence. Conclusions/interpretation The mtDNA 16189C variant is associated with an increased risk of type 2 diabetes in Asians. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Metabolic characteristics of women with polycystic ovaries and oligo-amenorrhoea but normal androgen levels: implications for the management of polycystic ovary syndrome

OBJECTIVE: Application of the newly introduced Rotterdam criteria for polycystic ovary syndrome (PCOS) generates four phenotypic subgroups, defined by the presence/absence of three diagnostic elements: polycystic ovarian (PCO) morphology (P); hyperandrogenism (H); and oligo-amenorrhoea (O). Whilst PCOS is associated with adverse metabolic features, the strength of the association within individual subgroups is not established. We characterized the metabolic and endocrine profiles of PCOS women who are oligomenorrhoeic but normoandrogenaemic, and compared these to other PCOS women and controls. DESIGN: Retrospective dataset analyses. PATIENTS: A total of 309 Europid PCOS women, all with PCO morphology, of whom 191 were also hyperandrogenaemic and oligomenorrhoeic (PHO), 76 hyperandrogenaemic with normal menses (PH) and 42 oligomenorrhoeic but normoandrogenaemic (PO); plus 76 Europid control women without PCOS. MEASUREMENTS: Metabolic parameters: fasting insulin, lipids, homeostasis model assessment (HOMA) measures of insulin sensitivity; endocrine variables: LH, FSH; prevalence of metabolic syndrome. RESULTS: Insulin sensitivity: PO women were indistinguishable from controls, and markedly less insulin-resistant than PHO women (vs. controls, P = 0.38 after adjustment for BMI and age; vs. PHO, P = 0.003). Metabolic syndrome: the prevalence in PO women (7.1%) was similar to that in controls (3.9%), and lower than in PHO women (29.3%, P < 0.0001). LH levels: PO women were intermediate between controls (vs. controls, P = 0.008) and PHO women (vs. PHO, P = 0.06). CONCLUSIONS: Normoandrogenaemic, oligomenorrhoeic women with PCOS are metabolically similar to control women with significantly fewer metabolic features than PCOS women who are also hyperandrogenaemic. However, higher than normal LH and lower sex hormone-binding globulin (SHBG) concentrations in the PO women support the view that they form part of the spectrum of PCOS.     

线粒体DNA变异与老年2型糖尿病患者易感性的相关性

目的 研究湖北地区老年2型糖尿病(T2DM)患者中线粒体基因突变的发生率及其相关性.方法 采用PCR-RFLP、基因测序技术,对175例老年T2DM患者和200例糖耐量正常的健康老年对照组进行检测.结果 MIND1 3316(G→A)、MTTL1 3243(A→G)、MIND13394( T→C)、MIND14216(T→C) MIND14164(A→G)和MIND2 5178( T→C)变异率分别为3.26％、2.72％、1.71％、4％、34.9％;对照组检出3316(G→A)突变2例(0.99％)、4164 5例(0.99％)、5718(T→C)变异64例(32.3％),未检出3394、4216的点突变;两组间3394(T→C)变异率差别有统计学意义(P＜0.05);且T2DM组5178A基因型血清TC水平低于5178C基因型(P＜0.05),但TG、LDL-C、HDL-C、apoA、apoB、Lp(a)水平两组无统计学意义.结论 3394( T→C)与老年T2DM患者的易感性有一定关联,5178(T→C)变异与湖北地区老年汉族人T2DM的脂代谢相关.     

Relationships between desacylated and acylated ghrelin and insulin sensitivity in the metabolic syndrome

CONTEXT: Metabolic syndrome shows clustered metabolic abnormalities with major roles for insulin resistance and obesity. Ghrelin is a gastric hormone whose total plasma concentration (T-Ghr) is associated positively with insulin sensitivity and is reduced in obesity. Ghrelin circulates in acylated (A-Ghr) and desacylated (D-Ghr) forms, but their potential differential associations with insulin resistance and whether they are differentially altered in obesity remain undefined. OBJECTIVE: Our objective was to determine potential differential associations of ghrelin forms with insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] and the impact of obesity on their plasma concentrations in metabolic syndrome. DESIGN: This is a cross-sectional study. SETTING: The study was performed in a metabolic outpatient unit. PATIENTS: Patients with metabolic syndrome (National Cholesterol Education Program-Adult Treatment Panel III; n = 45, 23 males/22 females) were included in the study. MAIN OUTCOMES: The main study outcomes were metabolic syndrome criteria, HOMA-IR, and ghrelin forms. RESULTS: Plasma insulin and HOMA-IR were associated negatively with T-Ghr and D-Ghr but positively with A-Ghr and acylated to desacylated ghrelin (A/D-Ghr) ratio (n = 45; P < 0.05). Compared with nonobese [body mass index (BMI) < 27.5 kg/m(2); n = 12, six males/six females], obese metabolic syndrome patients (BMI > 27.5 kg/m(2); n = 33) had lower T-Ghr and D-Ghr but comparable A-Ghr and higher A/D-Ghr ratio (P < 0.05). BMI and waist circumference (WC) were positively related with HOMA-IR (n = 45; P < 0.05). However, opposite associations between A/D-Ghr ratio and HOMA-IR remained significant after adjustment for sex and BMI (or WC). Additional obese individuals without metabolic syndrome (n = 10: age-, sex-, BMI-, and WC-matched to obese metabolic syndrome patients) had lower T-Ghr but higher A-Ghr (P < 0.05) compared with age-, sex-matched healthy nonobese counterparts (n = 15). T-Ghr and A-Ghr were comparable in obese with or without metabolic syndrome. CONCLUSION: Obesity could alter circulating ghrelin profile, and relative A-Ghr excess could contribute to obesity-associated insulin resistance in metabolic syndrome.     

体重指数在老年代谢综合征人群中诊断价值的初步探讨

目的了解老年人群中体重指数（BMI）与代谢综合征患病及相关代谢异常之间的关系。方法683例65岁以上（平均71．2岁）的老年男性,以中华医学会糖尿病学分会制订的代谢综合征工作定义作为标准,按照BMI进行分层,分析不同BMI人群代谢综合征的患病率及各项代谢指标的异常情况。结果（1）当BMI≥123kg／m^2时,代谢综合征的患病率随BMI的增加显著上升,BMI和代谢异常数量之间呈现一种正相关趋势（r=0．557）;（2）BMI增加与收缩压（SBP）、舒张压（DBP）、血甘油三酯之间正相关（r值分别为0．189、0．198和0．201）,与血高密度脂蛋白胆固醇之间负相关（r=-0．157）;（3）在血压正常人群和在非糖尿病人群,BMI与SBP、DBP、空腹血糖及餐后2h血糖之间显著正相关;（4）冠心病和肾脏损害患者的BMI显著高于无相关疾病人群（P〈0．05）;（5）冠心病、肾脏损害和脑血管病变患者中的代谢综合征患病率显著高于没有这些疾病的人群（P〈0．05）。结论随着BMI的增加,代谢指标异常的数量逐渐增加,代谢综合征的患病率也逐渐升高。BMI的增加与冠心病、肾脏损害和脑血管病变的发病相关。     

老年2型糖尿病并存非酒精性脂肪性肝病患者体成分及危险因素分析

目的 对老年2型糖尿病合并与未合并非酒精性脂肪性肝病患者体成分、血脂、腹型肥胖和代谢综合征发生率等进行比较,探讨合并非酒性脂肪性肝病的可能危险因素.方法 将入选老年2型糖尿病患者分为合并非酒精性脂肪性肝病组(脂肪肝组)83例及未合并非酒精性脂肪性肝病组(非脂肪肝组)85例,比较两组体成分、血脂、腹型肥胖和代谢综合征发生率等临床资料. 结果 脂肪肝与非脂肪肝组比较,组体质指数[(26.9±2.5)kg/m~2对(24.1±2.5j)kg/m~2,P=0.000]、腰臀围比(0.92±0.07对0.87±0.06,P=0.000)、总体脂肪比[(29.6±6.6)%对(25.3±5.5)%,P=0.000]、腹部脂肪[(11.0±2.5)kg对(8.7±2.3)kg,P=0.000]、内脏脂肪[(3.0±0.7)kg对(2.3±0.6)kg,P=0.000]、内脏脂肪面积[(97.6±22.2)cm~2对(75.5±21.1)cm~2,P=0.000]、三酰甘油[(1.98±0.94)mmol/L对(1.22±0.61)mmol/L,P=0.000]均升高,高密度脂蛋白胆醇[(1.23±0.32)mmol/L对(1.40±0.37)mmol/L,P=0.002]水平降低,差异均有统计学意义;体脂过高(68.7%对36.5%,P=0.000)、血脂异常(47.0%对21.2%,P=0.000)、腹型肥胖(69.9%对43.5%,P=0.001)和代谢综合征(49.4%对9.6%,P=0.000)的发病率亦明显升高,差异均有统计学意义;而总胆醇[(4.93±0.94)mmol/L对(4.73±1.07)mmol/L,P=0.219]和低密度脂蛋白胆固醇[(3.23±0.80)mmol/L对(3.07±0.89)mmol/L,P=0.229]两组比较,差异无统计学意义.Logistic回归分析显示体质指数超标(β=1.268,P=0.000,OR=3.56)、总体脂肪比过高(β=0.902,P=0.023,OR=2.47)和代谢综合征(β=1.664,P=0.000,OR=5.28)与老年2型糖尿病患者合并非酒精性脂肪性肝病相关. 结论 体质指数超标、总体脂肪比过高与老年2型糖尿病患者合并非酒精性脂肪性肝病相关,非酒精性脂肪性肝病可能是代谢综合征的一个组成部分.     

Clinical correlation of gallstone disease in a Chinese population in Taiwan： Experience at Cheng Hsin General Hospital

AIM: To explore the prevalence of gallstone disease (GSD) in Taiwan and condition-associated factors related to it. METHODS: We studied a total of 2386 healthy adults (1235 males and 1151 females) voluntarily admitted to Cheng Hsin General Hospital for a paid physical check-up between January 2002 and December 2002. Blood samples and ultrasound sonography results were collected. RESULTS: The overall prevalence of GSD among this study-population was 5.3%, including 1.7% (n=40) having a single stone, 2.3% (n=55) having multiple stones, and 1.3% (n=31) having cholecystectomy. The prevalence revealed a statistically significant increase with increasing age (P<0.0001). Females exhibited a greater prevalence of multiple stones than did males (3.0% vs 1.7%, P=0.04). Using multiple logistic regression analysis, the following appeared to be significantly related to the prevalence of GSD: older age (40-49 years vs < 40 years, OR=1.63 [95% CI: 0.76-3.48], 50-59 years vs < 40 years, OR=4.93 [95% CI: 2.43-9.99], 60-69 years vs < 40 years, OR=6.82 [95% CI: 3.19-14.60], > or = 70 years vs < 40 years, OR=10.65 [95% CI: 4.78-23.73]), higher BMI (> or = 27 kg/m2 vs < 24 kg/m2, adjusted OR=1.74 [95% CI: 1.04-2.88]), and higher FPG (> or = 126 mg/dL vs < 110 mg/dL, OR=1.71, 95%CI: 1.01-2.96). CONCLUSION: Older age (> or = 50 years), obesity (BMI > or = 27 kg/m2), and type 2 diabetes (FPG > or = 126 mg/dL) are associated with the prevalence of GSD.     

Polymorphisms in the interleukin-6 receptor gene are associated with body mass index and with characteristics of the metabolic syndrome

OBJECTIVE: Low-grade inflammation has been related to obesity, insulin resistance and the metabolic syndrome. The Asp358Ala variant and the CA-repeat polymorphism in the interleukin-6 receptor (IL-6R) gene have been reported to be associated with obesity in Pima Indians and Spanish women, respectively. The aim of this study was to investigate the association between these polymorphisms and obesity in a Mediterranean-Caucasian population, and to determine whether this polymorphism was related to the metabolic syndrome as defined by the National Cholesterol Education Program - Adult Treatment Panel III (NCEP/ATP-III) criteria. DESIGN: Cross-sectional. PATIENTS: Three hundred and ninety subjects from the general population. METHODS: The Asp358Ala and CA-repeat polymorphisms were analysed by polymerase chain reaction (PCR) amplification, followed by restriction fragment length polymorphism or capillary electrophoresis, respectively. RESULTS: Both polymorphisms were in strong linkage disequilibrium, Asp358 alleles being associated with 149 CA-repeat alleles (chi2 = 76.275, P < 0.0001). Therefore, only the association of the Asp358Ala variant with obesity and the metabolic syndrome was assessed in the whole series of subjects. Subjects homozygous for Asp358 alleles had statistically higher body mass index (BMI) compared with Ala358 carriers (27.7 +/- 5.41 vs. 26.6 +/- 4.96 kg/m2; P < 0.05). Moreover, the prevalence of the metabolic syndrome was significantly higher in carriers of the Asp358 allele compared with Ala358 homozygotes (12.7%vs. 0.0%; P = 0.01). This relationship remained significant after adjusting for age, insulin resistance, sex and BMI. CONCLUSIONS: The Asp358Ala and CA-repeat polymorphisms in the IL-6R gene are associated with obesity and characteristics of the metabolic syndrome in our population of Mediterranean subjects.     

Metabolic syndrome in Japanese patients with obstructive sleep apnea syndrome.

We investigated the prevalence of metabolic syndrome in patients with obstructive sleep apnea syndrome (OSAS) referred to a tertiary university-based medical center. A cross-sectional study of patients with a definite diagnosis of OSAS was performed using new diagnostic criteria for metabolic syndrome that were designed for the Japanese population. Clinical features and comorbidities related to metabolic syndrome were compared between 819 patients with OSAS (719 men and 100 women) and 89 control subjects without OSAS. Metabolic syndrome was significantly more common in the patients with OSAS than in the controls (49.5% vs. 22.0% for men, p < 0.01; 32.0% vs. 6.7% for women, p < 0.01). Men with OSAS (apnea-hypopnea index [AHI] > or =5/h) had a higher risk of metabolic syndrome compared with controls (odds ratio [OR]: 3.47; 95% confidence interval [CI]: 1.84-6.53). There was a significantly increased risk of metabolic syndrome in men with moderate OSAS (AHI: 15-29.9/h) (OR: 2.83; 95% CI: 1.42-5.66) and men with severe OSAS (AHI > or =30/h) (OR: 5.09; 95% CI: 2.67-9.71). Women with OSAS (AHI> or =5/h) also had an increased risk of metabolic syndrome (OR: 6.59; 95% CI: 1.47-29.38), and the risk was significantly higher in women with severe OSAS (AHI > or =30/h) (OR 14.00; 95% CI: 2.93-66.82). Risk factors for metabolic syndrome differed by gender: in men, age, body mass index (BMI), and OSAS (AHI > or =15/h) were significantly associated with metabolic syndrome, whereas, in women, BMI was the only risk factor for metabolic syndrome. The increase of metabolic syndrome in Japanese OSAS patients suggests that this patient population is burdened with multiple risk factors for cardiovascular disease.     

Low high-density lipoprotein-cholesterol is the most prevalent metabolic abnormality for Australian Aboriginal men and women even when lean.

BACKGROUND: The aim of this study was to investigate the relationship of the prevalence and risk of the metabolic syndrome to body mass index (BMI) in Australian Aboriginal people. DESIGN: It was a cross-sectional, secondary analysis of data obtained from population-based screenings in Aboriginal communities in central and northern Australia (913 participants recruited between 1993 and 1997). RESULTS: Forty-one percent of men and 48% of women conformed to the National Cholesterol Education Program definition for the metabolic syndrome (chi2=3.72, P=0.054). The prevalence of low high-density lipoprotein-cholesterol was high in all BMI categories (89 and 95% in men and women, respectively). The prevalence of all other metabolic abnormalities increased linearly with BMI. CONCLUSION: The metabolic syndrome is highly prevalent in Aboriginal communities and is strongly associated with BMI. Low high-density lipoprotein-cholesterol was the predominant component of the metabolic syndrome across sex groups and BMI strata.     

Nonalcoholic fatty liver,steatohepatitis, and the metabolic syndrome

Nonalcoholic fatty liver disease (NAFLD) has been associated with the insulin-resistance syndrome, at present defined as the metabolic syndrome, whose limits were recently set. We assessed the prevalence of the metabolic syndrome in 304 consecutive NAFLD patients without overt diabetes, on the basis of 3 or more criteria out of 5 defined by the U.S. National Institutes of Health (waist circumference, glucose, high-density lipoprotein [HDL]-cholesterol, triglycerides, and arterial pressure). The prevalence of the metabolic syndrome increased with increasing body mass index, from 18% in normal-weight subjects to 67% in obesity. Insulin resistance (Homeostasis Model Assessment method) was significantly associated with the metabolic syndrome (odds ratio [OR], 2.5; 95% CI, 1.5-4.2; P <.001). Liver biopsy was available in 163 cases (54%). A total of 120 patients (73.6%) were classified as having nonalcoholic steatohepatitis (NASH); 88% of them had a metabolic syndrome (vs. 53% of patients with pure fatty liver; P <.0001). Logistic regression analysis confirmed that the presence of metabolic syndrome carried a high risk of NASH among NAFLD subjects (OR, 3.2; 95% CI, 1.2-8.9; P =.026) after correction for sex, age, and body mass. In particular, the syndrome was associated with a high risk of severe fibrosis (OR, 3.5; 95% CI, 1.1-11.2; P =.032). In conclusion, the presence of multiple metabolic disorders is associated with a potentially progressive, severe liver disease. The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension, and ultimately the metabolic syndrome puts a very large population at risk of forthcoming liver failure in the next decades.     

Metformin administration and laparoscopic ovarian drilling improve ovarian response to clomiphene citrate (CC) in oligo-anovulatory CC-resistant women with polycystic ovary syndrome

OBJECTIVE: To compare the efficacy of clomiphene citrate (CC) administration for ovulation induction in CC-resistant oligo-ovulatory women with polycystic ovary syndrome (PCOS) after metformin treatment or laparoscopic ovarian drilling (LOD). Design Prospective controlled study. PATIENTS: Twenty-eight overweight oligo-amenorrhoeic women with PCOS who were still anovulatory after metformin administration (group A, n = 8) or LOD (group B, n = 20). METHODS: Treatment with CC 150 mg/day for 5 days from the third to the seventh day of a progesterone-induced uterine bleeding for 6 months. MEASUREMENTS: The ovulation, pregnancy, abortion and live-birth rates were evaluated in each group. RESULTS: The subjects of groups A and B were studied for a total of 36 and 74 cycles, respectively. At the end of the study, no differences in ovulation [11/36 (30.6%) vs. 23/74 (31.1%); P = 0.96], pregnancy [6/36 (16.7%) vs. 12/74 (16.2%); P = 0.95], abortion [2/6 (33.3%) vs. 5/12 (41.7%); P = 1.00] and the live-birth [4/6 (66.7%) vs. 7/12 (58.3%); P = 1.00] rates were observed between groups A and B. CONCLUSION: Metformin administration as well as LOD improves the effectiveness of CC for ovulation induction in overweight infertile CC-resistant women with PCOS.