脂肪因子与代谢综合征关系的研究进展

代谢综合症是一系列代谢和心血管功能失调的临床特征,包括中心性肥胖、高血压、血脂异常、高血糖及胰岛素抵抗等,其发病机制及如何预防及控制代谢综合症正日益成为目前的学术热点。目前已经公认,脂肪不仅是能量存储器官,也是一个重要的内分泌器官。脂肪组织分泌的生物活性分子被称为脂肪因子。近年来的研究表明,脂肪因子广泛参与肥胖、2型糖尿病、高血压病及心血管疾病等一系列代谢相关性疾病的病理生理过程。脂肪因子能通过介导一系列的信号转导通路,并广泛参与机体复杂的代谢平衡网络的调节。脂肪因子的失衡能导致机体发生对胰岛素敏感性改变等一系列的生物学反应,从而在肥胖和代谢综合症的病理过程中发挥重要的作用。本文综述了脂肪因子与代谢综合征的关系的研究进展。     

微量白蛋白尿与2型糖尿病合并代谢综合征的相关性

目的:探讨2型糖尿病(T2DM)患者微量白蛋白尿与代谢综合征(MS)的相关性。方法:282例T2DM患者根据是否合并MS分为MS组(163例)和非MS组(119例),测定24h尿白蛋白(UAlb)及相关生化指标,比较两组UAlb水平及糖尿病肾病(DN)患病率,采用多元Logistic回归方法分析T2DM患者微量白蛋白尿的危险因素。结果:MS组的UAlb及DN患病率明显高于非MS组,且随着MS组分增加,UAlb水平显著升高。多元Logistic回归分析表明甘油三酯、糖化血红蛋白、收缩压为影响UAlb的独立危险因素。结论:T2DM患者微量白蛋白尿与MS密切相关,需采取综合干预措施避免或延缓DN的发生发展。     

微量白蛋白尿与2型糖尿病合并代谢综合征的相关性

目的:探讨2型糖尿病(T2DM)患者微量白蛋白尿与代谢综合征(MS)的相关性.方法:282例T2DM患者根据是否合并MS分为MS组(163例)和非MS组(119例),测定24h尿白蛋白(UAlb)及相关生化指标,比较两组UAlb水平及糖尿病肾病(DN)患病率,采用多元Logistic回归方法分析T2DM患者微量白蛋白尿的危险因素.结果:MS组的UAlb及DN患病率明显高于非MS组,且随着MS组分增加,UAlb水平显著升高.多元Logistic回归分析表明甘油三酯、糖化血红蛋白、收缩压为影响UAlb的独立危险因素.结论:T2DM患者微量白蛋白尿与MS密切相关,需采取综合干预措施避免或延缓DN的发生发展.     

Association between Family History Risk Categories and Prevalence of Diabetes in Chinese Population

AimTo investigate the association between different family history risk categories and prevalence of diabetes in the Chinese population.MethodsThe family history of diabetes was obtained from each subject, and an oral glucose tolerance test was performed for measuring the fasting and postload glucose and insulin levels based on a national representative cross-sectional survey of 46,239 individuals (age ≥ 20 years) in the 2007–2008 China National Diabetes and Metabolism Disorders Study. The family history risk categories of diabetes were high, moderate, and average (FH2 and FH1: at least two generations and one generation of first-degree relatives with diabetes, respectively; FH0: no first-degree relatives with diabetes).ResultsThe age- and gender-adjusted prevalence rates of diabetes were 32.7% (95% confidence interval (CI): 26.4–39.7%) in FH2, 20.1% (95% CI: 18.2–22.1%) in FH1, and 8.4% (95% CI: 7.9–8.9%) in FH0 (P < 0.0001). The calculated homeostatic model assessment-estimated insulin resistance (HOMA-IR), Matsuda insulin sensitivity index (ISI), and insulinogenic index (ΔI30/ΔG30) values showed significant trending changes among the three risk categories, with the most negative effects in FH2. Multivariate logistic regression analysis showed that the odds ratios of having diabetes were 6.16 (95% CI: 4.46–8.50) and 2.86 (95% CI: 2.41–3.39) times higher in FH2 and FH1, respectively, than in FH0 after adjustment for classical risk factors for diabetes.ConclusionsFamily history risk categories of diabetes have a significant, independent, and graded association with the prevalence of this disease in the Chinese population.     

The Association between Self-Reported Sleep Quality and Metabolic Syndrome

Objectives

Short and long sleep duration are associated with metabolic syndrome. However, there is limited research on the association between sleep quality and metabolic syndrome, and thus the aim of this study is to investigate this relationship.

Materials and Methods

The cross-sectional baseline data were collected from the decoded database of the Prevention Health Center of National Cheng Kung University Hospital from 2002 to 2006. The diagnosis of metabolic syndrome was according to the statement of the American Heart Association/National Heart, Lung, and Blood Institute. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). A higher global PSQI score indicates poorer sleep quality, and a global PSQI score greater than five differentiates poor from good sleepers.

Results

Of the 3,435 subjects recruited, 899 (26.2%) had metabolic syndrome. Subjects with metabolic syndrome had higher PSQI and prevalence of poor sleepers than those without metabolic syndrome. The multivariate lineal regression analysis showed that female gender, metabolic syndrome, sleep duration, snoring, alcohol drinking, and habitual exercise were independent predictors of PSQI. When substituting metabolic syndrome with the five components, hyperglycemia and low high-density lipoprotein cholesterol (HDL-C) were positively associated with PSQI. The multivariate logistic regression analyses showed that female gender, metabolic syndrome, sleep duration, and snoring were independently associated with being poor sleepers. Of the five components, only low HDL-C was an independent predictor of being poor sleepers.

Conclusions

Subjects with metabolic syndrome have higher global PSQI scores and a higher risk of being poor sleepers. Of the five components of metabolic syndrome, hyperglycemia and low HDL-C are independently associated with the global PSQI scores, while low HDL-C is an independent predictor of being poor sleepers.     

Impact of Family History of Diabetes on Diabetes Control and Complications

Objective: Our aim was to assess the impact of parental and sibling history of type 2 diabetes (T2D) on patient characteristics, glycemic control, and T2D complications.Methods: This cross-sectional study included adults with T2D. Type 1 diabetes and gestational diabetes patients were excluded. The laboratory data were retrieved from the patients' electronic files, and baseline measurements were obtained by the researchers.Results: The study included a total of 511 T2D patients, with a mean age of 60.1 ± 10.9 years and mean hemoglobin A1c of 8.94 ± 2.1% (74.2 ± 22.9 mmol/mol). Of these patients, 54% were male and 49.7% had a parental history of T2D. The patients with parental history of T2D were diagnosed at a younger age and had a higher body mass index (BMI) (P =.035) and higher waist circumference (WC) (P =.013) than those T2D patients with no parental history. Approximately 60% of the participants had siblings with a history of T2D, and in comparison with those with no sibling history, they had higher prevalence of cerebrovascular accidents (P =.02).Conclusion: Having a parental history of T2D is significantly associated with diagnosis at a younger age and a higher BMI and WC. Having a sibling history of T2D is significantly associated with worse cerebrovascular outcome.Abbreviations: ACR = albumin to creatinine ratio; BMI = body mass index; DBP = diastolic blood pressure; DM = diabetes mellitus; FBG = fasting blood glucose; GFR = glomerular filtration rate; HbA1c = hemoglobin A1c; LDL = low-density lipoprotein; SBP = systolic blood pressure; T2D = type 2 diabetes; TG = triglyceride; WC = waist circumference     

The Glucocorticoid Receptor Gene and Its Association to Metabolic Syndrome

In recent decades, there has been an increasing interest in the role of endogenous glucocorticoids such as cortisol in the pathogenesis of metabolic syndrome. Studies in humans have suggested a positive association between obesity, hypertension, and insulin resistance, with alleles at the glucocorticoid receptor (GR) gene. For instance, the BclI polymorphism within the intron upstream of GR exon 2 has been associated with cardiovascular risk factors such as visceral obesity, hypertension, insulin resistance, and elevated cortisol concentrations. However, the location of the BclI polymorphism is not known, and the variant has so far not been compared with the wild-type receptor for its ability to be activated by glucocorticoids. Although several other mutations in the GR gene have been postulated as being relevant to the progression to type 2 diabetes and cardiovascular diseases, conflicting results makes it difficult to determine exactly what effect these GR variations have on metabolic syndrome incidence and progression. Further studies focusing on the most compelling GR mutations might offer a better understanding of metabolic syndrome pathogenesis and progression, aiding in the development of more effective treatments for this condition.     

Colesevelam Hydrochloride-Ezetimibe Combination Lipid-Lowering Therapy in Patients with Diabetes or Metabolic Syndrome and a History of Statin Intolerance

ObjectiveTo determine the effectiveness and safety of colesevelam hydrochloride (HCl) and ezetimibe combination therapy in statin-intolerant patients with dyslipidemia and diabetes mellitus (DM) or metabolic syndrome (MS).MethodsWe identified potential study subjects through a computerized text search of patient electronic medical records using the terms colesevelam, WelChol, ezetimibe, and Zetia. Medical records were subsequently reviewed to identify all patients with DM or MS. Baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglyceride levels immediately before the initiation of therapy with colesevelam HCl (1.875 g twice a day) or ezetimibe (10 mg daily) were compared with those after a minimum of 3 months of single drug therapy and after a minimum of 3 months of combination therapy. Drug safety was evaluated by review of transaminase levels and reports of side effects or drug discontinuation.ResultsThe computerized search initially identified 91 electronic medical records; 16 patients fulfilled all study criteria. Baseline patient demographics included a mean age of 62.5 (± 11.8) years and a mean body mass index of 31.4 (± 5.2) kg/m²; 50% of patients were female, 75% had type 2 DM, and 25% had MS. In comparison with baseline, colesevelam HCl-ezetimibe combination therapy was associated with significant reductions in mean levels of total cholesterol (27.5%), LDL-C (42.2%), and non-HDL-C (37.1%). In addition, 50% of patients achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C target of less than 100 mg/dL. Therapy was well tolerated, with no significant changes in mean transaminase levels, no reports of myalgia, and no discontinuation of therapy.ConclusionColesevelam HCl-ezetimibe combination therapy was associated with improved TC, LDL-C, and non-HDL-C lipid profiles and was well tolerated. Such therapy may be a reasonable consideration for statin-intolerant patients with DM or MS who have elevated cholesterol levels. (Endocr Pract. 2007;13:11-16)     

The Relationship Between Menopause and Metabolic Syndrome: Experimental and Bioinformatics Analysis

Biochemical Genetics - Menopausal hormonal changes have been associated with the emergence of the metabolic syndrome (MetS) and its consequences such as type 2 diabetes (T2D) and cardiovascular...     

The Association of Homocysteine with Metabolic Syndrome in a Community-Dwelling Population: Homocysteine Might Be Concomitant with Metabolic Syndrome

Objective

Elevated plasma total homocysteine (tHcy) and metabolic syndrome (MetS) are both associated with cardiovascular disease, but the association between tHcy and MetS is not well characterized. The aim of this study was to determine the relationship between tHcy and MetS.

Methods

To further estimate the time-dependent association of tHcy and MetS, we analyzed the tHcy level and MetS in 1499 subjects from a 4.8-year longitudinal study in Beijing, People’s Republic of China.

Results

In multiple linear regression analysis, baseline tHcy levels associated with age, BMI, SBP, DBP, LDL-C and Cr independently over 4.8-years follow-up; age, BMI, SBP, DBP and Cr were found to be associated with tHcy levels independently at the end of follow-up. Logistic regression analysis showed that there was no association between the baseline tHcy level and MetS over the 4.8-year follow-up (odds ratio (OR), 1.32; 95% confidence interval (CI), 0.79–2.19; P = 0.282); rather, there was an association only with hypertension as a MetS component (OR, 1.53; 95% CI, 1.06–2.21; P = 0.024). tHcy levels were associated with MetS at both cross-sectional baseline (OR, 1.38; 95% CI, 1.02–1.88; P = 0.038) and cross-sectional follow-up (OR, 1.60; 95% CI, 1.02–2.50; P = 0.041). The tHcy levels of MetS subjects were higher than those of non-MetS subjects at both cross-sectional baseline (19.35±7.92 µmol/L vs. 17.45±6.70 µmol/L, respectively; P = 0.001) and cross-sectional follow-up (18.95±7.15 µmol/L vs. 17.11±5.98 µmol/L, respectively; P = 0.02).

Conclusion

The tHcy level was not predictive of the incidence of MetS; however, it may be a risk factor for hypertension as a MetS component. Furthermore, tHcy levels were associated with MetS at cross-sectional baseline and follow-up, which suggests that a higher level of tHcy might be concomitant with MetS.     

Insulin Sensitivity,Body Fat Distribution,and Family Diabetes History: The IRAS Family Study

Objectives : Markers of insulin resistance are often apparent in nondiabetic relatives of subjects with type 2 diabetes. Whether diabetes family history (FH) also predicts visceral fat accumulation and, if so, whether the increased insulin resistance in relatives of diabetic subjects occurs independently of visceral fat accumulation are not known. Research Methods and Procedures : To examine this issue, we studied the relationship of diabetes FH with insulin sensitivity and fat measures, measured by minimal model analysis and computed tomography, respectively, in families participating in the Insulin Resistance Atherosclerosis (IRAS) Family Study. FH scores were based on the diabetes status of the participants’ parents and older siblings. Results : FH scores were significantly correlated with reduced insulin sensitivity (p < 0.05) and increased subcutaneous (p < 0.05) and visceral (p < 0.05, San Antonio only) fat in families from San Antonio and Los Angeles but not in the leaner Hispanic families from San Luis Valley. There was no evidence for a stronger association of FH score with visceral fat accumulation than with subcutaneous fat or insulin resistance. Discussion : The absence of an association between FH score and insulin resistance/fat accumulation in San Luis Valley is consistent with the idea that the expression of transmitted diabetes genes may be suppressed in leaner, more physically active populations.     

代谢综合征与非酒精性脂肪肝临床特征的关系

目的:探讨代谢综合征(metabolic syndrome,MS)与非酒精性脂肪肝(non-alcoholic fatty liver disease,NAFLD)临床特征之间的相关性。方法:从我院2012年1月-2014年2月健康体检资料中抽选326例经超声确诊为NAFLD的患者,作为NAFLD组,并随机抽选335例无脂肪肝患者作为对照组;观察两组患者间的临床特征,并采用Logistic回归分析MS与NAFLD临床特征之间的相关性。结果:NAFLD组患者体重指数(BMI)、血压、丙氨酸氨基转移酶(ALT)、空腹血糖(FBG)、血尿酸(UA)、高密度脂蛋白(HDL-C)、甘油三酯(TG)、天冬氨酸氨基转移酶(AST)水平显著高于对照组(P0.05):两组间低密度脂蛋白(LDL-C)、总胆固醇(TC)比较无显著性(P0.05)。NAFLD组中MS、血脂及糖代谢异常、肥胖以及高血压的检出率明显高于对照组(P0.05)。经Logistic回归分析显示,NAFLD、BMI、TG、HDL-C、高血压及血糖是MS的独立危险因素。结论:NAFLD患者中存在MS的各种组分聚集特征,MS患病率明显升高,NAFLD是MS的独立危险因素之一,因此MS与NAFLD关系密切。     

The Quantitative Relationship Between Autonomous Cortisol Secretion,Dysglycemia and the Metabolic Syndrome

Objective: Autonomous cortisol secretion (ACS) is the most common endocrine abnormality in the evaluation of adrenal incidentalomas. The categorization of ACS is derived from a 1 mg dexamethasone suppression test (DST). Impaired DST is associated with several metabolic derangements. In this study we analyzed the association between post-DST cortisol level, analyzed as a continuous parameter, and indices of glycemic metabolism.Methods: We prospectively collected data of 1,976 patients evaluated for adrenal incidentalomas in a large tertiary medical center between December 1, 2017, and August 31, 2019. Seventy-three patients completed the evaluation process. Post-DST cortisol levels were analyzed for correlation with various metabolic parameters, including fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) among the general cohort and for subgroups stratified by the number of metabolic syndrome (MS) criteria.Results: Post-DST cortisol demonstrated a linear association with FPG and HbA1c across its entire cortisol range (R = 0.51 and 0.41, respectively; P≤.01). The association between post-DST cortisol and FPG was strengthened with an increased number of metabolic syndrome criteria. Patients with 4 MS criteria show a stronger association (R = 0.92) compared to patients with only a single criterion (R = 0.509). Furthermore, mean post-DST cortisol levels increased as the number of MS criteria accumulated.Conclusion: Post-DST cortisol should be viewed as a continuous parameter in risk stratification algorithms for the development of MS and particularly dysglycemia.     

Association of Hepatocyte Nuclear Factor 4 Alpha Polymorphisms with Type 2 Diabetes With or Without Metabolic Syndrome in Malaysia

This study investigated the association of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) with type 2 diabetes with or without metabolic syndrome in Malaysia. Nine HNF4 alpha SNPs were genotyped in 390 type 2 diabetic subjects with metabolic syndrome, 135 type 2 diabetic subjects without metabolic syndrome, and 160 control subjects. The SNPs rs4810424, rs1884613, and rs2144908 were associated with protection against type 2 diabetes without metabolic syndrome (recessive P = 0.018, OR 0.32; P = 0.004, OR 0.25; P = 0.005, OR 0.24, respectively). The 6-SNP haplotype2 CCCGTC containing the risk genotype of these SNPs was associated with higher risk for type 2 diabetes with or without metabolic syndrome (P = 0.002, OR 2.2; P = 0.004, OR 3.1). These data suggest that HNF4 alpha SNPs and haplotypes contributed to increased type 2 diabetes risk in the Malaysian population.     

Metabolic Syndrome Risk after Gestational Diabetes: A Systematic Review and Meta-Analysis

Background

A number of studies have been conducted to investigate the risk of metabolic syndrome (MS) after gestational diabetes mellitus (GDM), but the results are contradictory. Accordingly, we performed a systematic review and meta-analysis to assess the association between these two conditions. The aim was to better understand the risks of MS with prior gestational diabetes.

Methods

Pubmed, ISI Web of Science, and Cochrane databases from September 1, 1979 to July 11, 2013 were searched to identify relevant studies. 17 studies containing 5832 women and 1149 MS events were included. We calculated the odds ratio (OR) with 95% confidence interval (CI) in analysis for each study using a random-effect or fixed-effect model. We also determined heterogeneity among these 17 articles and their publication bias.

Results

Women with a history of gestational diabetes had a significantly higher risk of MS than those who had a normal pregnancy (OR, 3.96; 95% CI, 2.99 to 5.26), but had significant heterogeneity (I ² = 52.6%). The effect remained robust (OR, 4.54; 95% CI, 3.78–5.46) in the subgroup of Caucasians, but no association (OR, 1.28; 95% CI, 0.64–2.56) was found in Asians. Heterogeneity was reduced (body mass index (BMI) matched group I ² = 14.2%, BMI higher in the GDM group I ² = 13.2%) in the subgroup of BMI. In addition, mothers with higher BMI in the GDM group had higher risk of MS than those in the BMI matched group (BMI higher in GDM group OR, 5.39; 95% CI, 4.47–6.50, BMI matched group OR, 2.53; 95% CI, 1.88–3.41).

Conclusions

This meta-analysis demonstrated increased risk of MS after gestational diabetes. Therefore, attention should be given to preventing or delaying the onset of MS in GDM mothers, particularly in Caucasian and obese mothers.