Serum adiponectin level is not only decreased in metabolic syndrome but also in borderline metabolic abnormalities

Objective:

Along with the increasing prevalence of obesity and related diseases, particularly atherosclerotic diseases, metabolic syndrome (MetS) is now a common and major public health issue in many countries around the world. Adiponectin, a protein secreted by the adipose tissue, has become recognized as a key player in the development of MetS. These days, not only MetS but also borderline metabolic/physiological abnormalities, such as impaired fasting glucose, high normal blood pressure and high normal plasma cholesterol, have been reported to be risk factors for atherosclerotic disease. Therefore, we undertook this study to determine the relationship between adiponectin and borderline metabolic/physiological abnormalities, as well as MetS.

Design:

A cross-sectional study performed from April 2007 to November 2009.

Subjects:

In 16 892 Japanese adults (10 008 men and 6884 women), we examined the relationship between the serum adiponectin concentration and borderline metabolic/physiological abnormalities or MetS by a questionnaire survey about medical treatment, body size measurement and measurement of laboratory parameters including the serum adiponectin concentration.

Results:

Adiponectin showed a significant negative correlation with the number of MetS components. In subjects without overt diabetes mellitus, hypertension or dyslipidemia, the adiponectin concentration also showed a significant negative correlation with the number of borderline metabolic abnormalities.

Conclusion:

The decrease of circulating adiponectin may start before the development of diabetes mellitus, hypertension, dyslipidemia or MetS. Adiponectin is an important biomarker for reflecting the adverse influence of visceral fat in persons with MetS, and also in these subclinical states.     

Total bilirubin is inversely associated with metabolic syndrome but not a risk factor for metabolic syndrome in Japanese men and women

Serum total bilirubin (TB) is a potent antioxidant and inversely associated with metabolic syndrome (MetS) in Asian populations. However, there has been no study which is aimed to investigate whether TB is a risk factor for MetS or not. We investigated cross-sectional and longitudinal associations between TB and MetS in 2,435 Japanese men and 1,436 Japanese women. The odds ratios [95 % confidence interval (CI)] of coexisting MetS for each 1 SD increase in log TB were 0.850 (0.754–0.958) (p = 0.008) in men and 0.809 (0.656–0.998) (p = 0.047) in women adjusted for sex, age, smoking, and other confounding covariates. Those for the third and fourth quartiles of TB compared with the lowest quartile were 0.720 (0.537–0.965) (p = 0.028) and 0.737 (0.530–1.052) (p = 0.095), respectively, in men and 0.822 (0.473–1.427) (p = 0.486) and 0.704 (0.362–1.369) (p = 0.301), respectively, in women. There was a tendency that TB and MetS changed inversely to each other. The similarly adjusted hazard ratios of developing MetS for each 1 SD increase in log TB and for the higher quartiles of TB compared with the lowest quartile were not significant either in men or in women. TB is inversely associated with MetS but not a risk factor for MetS in Japanese men and women.     

Greater impairment of postprandial triacylglycerol than glucose response in metabolic syndrome subjects with fasting hyperglycaemia

Objective

Studies have started to question whether a specific component or combinations of metabolic syndrome (MetS) components may be more important in relation to cardiovascular disease risk. Our aim was to examine the impact of the presence of raised fasting glucose as a MetS component on postprandial lipaemia.

Methods

Men classified with the MetS underwent a sequential test meal investigation, in which blood samples were taken at regular intervals after a test breakfast (t = 0 min) and lunch (t = 330 min). Lipids, glucose and insulin were measured in the fasting and postprandial samples.

Results

MetS subjects with 3 or 4 components were subdivided into those without (n = 34) and with (n = 23) fasting hyperglycaemia (≥ 5.6 mmol/l), irrespective of the combination of components. Fasting lipids and insulin were similar in the two groups, with glucose significantly higher in the men with glucose as a MetS component (P < 0.001). Following the test meals, there were higher maximum concentration (maxC), area under the curve (AUC) and incremental AUC (P ≤ 0.016) for the postprandial triacylglycerol (TAG) response in men with fasting hyperglycaemia. Greater glucose AUC (P < 0.001) and insulin maxC (P = 0.010) were also observed in these individuals after the test meals. Multiple regression analysis revealed fasting glucose to be an important predictor of the postprandial TAG and glucose response.

Conclusion

Our data analysis has revealed a greater impairment of postprandial TAG than glucose response in MetS subjects with raised fasting glucose. The worsening of postprandial lipaemic control may contribute to the greater CVD risk reported in individuals with MetS component combinations which include hyperglycaemia.     

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

Aims/hypothesis Retinol-binding protein 4 (RBP4) has recently been reported to be associated with insulin resistance and the metabolic syndrome. This study tested the hypothesis that RBP4 is a marker of insulin resistance and the metabolic syndrome in patients with type 2 diabetes or coronary artery disease (CAD) or in non-diabetic control subjects without CAD. Methods Serum RBP4 was measured in 365 men (126 with type 2 diabetes, 143 with CAD and 96 control subjects) and correlated with the homeostasis model assessment of insulin resistance index (HOMA-IR), components of the metabolic syndrome and lipoprotein metabolism. RBP4 was detected by ELISA and validated by quantitative Western blotting. Results RBP4 concentrations detected by ELISA were shown to be strongly associated with the results gained in quantitative Western blots. There were no associations of RBP4 with HOMA-IR or HbA_1c in any of the groups studied. In patients with type 2 diabetes there were significant positive correlations of RBP4 with total cholesterol, LDL-cholesterol, VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity. In patients with CAD, there were significant associations of RBP4 with VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity, while non-diabetic control subjects without CAD showed positive correlations of RBP4 with VLDL-cholesterol and plasma triacylglycerol. Conclusions/interpretation RBP4 does not seem to be a valuable marker for identification of the metabolic syndrome or insulin resistance in male patients with type 2 diabetes or CAD. Independent associations of RBP4 with pro-atherogenic lipoproteins and enzymes of lipoprotein metabolism indicate a possible role of RBP4 in lipid metabolism.     

Partial normalization of components of metabolic syndrome does not influence prevalent echocardiographic abnormalities: The HyperGEN study

Background and aimsMetabolic syndrome (MetS) is a complex condition characterized by different phenotypes, according to the combinations of risk factors and is associated with cardiovascular abnormalities. Whether control of MetS components by treatment produces improvement in the associated cardiovascular abnormalities is unknown. We investigated whether partial control of components of MetS was associated with less echocardiographic abnormalities than the complete presentation of MetS based on measured components.Methods and resultsWe evaluated markers of echocardiographic preclinical cardiovascular disease in MetS (ATP III) defined by measured components or by history of treatment, in 1421 African-American and 1195 Caucasian non-diabetic HyperGEN participants, without prevalent cardiovascular disease or serum creatinine >2 mg/dL. Of 2616 subjects, 512 subjects had MetS by measured components and 328 by history. Hypertension was found in 16% of participants without MetS, 6% of those with MetS by history and 42% of those with MetS by measured components. Obesity and central fat distribution had similar prevalence in both MetS groups (both p < 0.0001 vs. No-MetS). Blood pressure was similar in MetS by history and No-MetS, and lower than in MetS by measured components (p < 0.0001). LV mass and midwall shortening, left atrial (LA) dimension and LA systolic force were similarly abnormal in both MetS groups (all p < 0.0001 vs. No-MetS) without difference between them.ConclusionsThere is a little impact of control by treatment of single components of MetS (namely hypertension) on echocardiographic abnormalities. Lower blood pressure in participants with MetS by history was not associated with substantially reduced alterations in cardiac geometry and function.     

Modifying the n-6/n-3 polyunsaturated fatty acid ratio of a high–saturated fat challenge does not acutely attenuate postprandial changes in inflammatory markers in men with metabolic syndrome

Metabolic syndrome (MetS) features chronic inflammation and exaggerated postprandial triacylglyceride (TAG) responses. Fasting concentrations of interleukin-6 (IL-6) and C-reactive protein (CRP), key inflammatory mediators, decrease after sustained n-3 polyunsaturated fatty acid (PUFA) intake; however, the ability of n-3 PUFA to attenuate postprandial inflammatory responses is not well studied. Thus, we examined the acute effect of modifying the n-6/n-3 PUFA ratio of a high–saturated fatty acid (SFA) oral fat tolerance test (OFTT) on postprandial TAG and inflammatory responses in men with MetS. Men (n = 8, ≥45 years old) with MetS ingested 2 high-SFA OFTTs (1 g fat per kilogram body weight), with either a 20:1 (low n-3) or 2:1 (high n-3) n-6/n-3 PUFA ratio, and a water control in a randomized crossover design. Blood samples were collected for 8 hours after treatment to measure postprandial TAG, free fatty acids, IL-6, soluble IL-6 receptor, and CRP. Postprandial TAG increased at the same rate after ingestion of the low–n-3 and high–n-3 OFTTs; however, both OFTTs were significantly different from the water control. There were no differences in the rate at which IL-6 concentrations increased after ingestion of either of the OFTTs compared with water. Furthermore, neither time nor treatment affected circulating soluble IL-6 receptor or CRP concentrations. Thus, increasing the n-3 PUFA content of a high-SFA OFTT does not acutely change postprandial TAG or inflammatory responses in men with MetS.     

A cross-sectional study on lifestyles and the metabolic syndrome (MetS) components mainly targeting glucose metabolism in Japanese working men

AimsThe prevalence of glucose intolerance in the Japanese adult population is increasing. In this study, the associated factors including lifestyles with glucose intolerance and its metabolism were explored.MethodsA cross-sectional study was conducted in 2008. The sample included 3203 working men aged 35–59 years. Age, six lifestyle-related factors, and metabolic components were used as variables to calculate the odds ratio for glucose intolerance, which were defined if his fasting plasma glucose was ≥110 mg/dL and <126 mg/dL.ResultsThe prevalence of glucose intolerance was 8.4%, and it increased with 5-year interval of age (2.2, 5.0, 10.4, 15.2, and 17.5%, respectively). Odds ratios (95% confidence interval) of age, obesity, hypertension, dyslipidemia, and no current smoking for glucose intolerance were 1.11 (1.09–1.13), 1.66 (1.31–2.11), 1.90 (1.47–2.47), 1.86 (1.46–2.36), and 0.79 (0.62–0.998), respectively. In contrast, the odds ratios of drinking, sleeping, exercise, and dietary habit did not reach the significance level, although multiple regression analysis presented that subjects with regular exercise showed significantly lower serum insulin level.ConclusionsThe risk of glucose intolerance was significantly correlated with obesity, high blood pressure, dyslipidemia and smoking habit. However, other lifestyle factors were not significantly associated with glucose intolerance.     

Elevated alanine aminotransferase is associated with metabolic syndrome but not consistently associated with impaired fasting glucose or type 2 diabetes mellitus

Background

Abnormally elevated alanine aminotransferase (ALT) of nonspecific causes is a common outpatient problem. Without considering ethnicity, several studies had suggested that it was associated with insulin resistance (IR).

Objective

To investigate whether nonspecific elevated ALT in Taiwanese population could reflect a likely underlying IR and was associated with impaired fasting glucose or type 2 diabetes mellitus (IFG/T2DM).

Methods

The health examination profiles of 1313 Taiwanese were investigated cross-sectionally. The prevalence and odds ratios (ORs) for IFG/T2DM and metabolic abnormalities in relation to elevated ALT were analyzed.

Results

Subjects with metabolic syndrome (MS) all had IFG/T2DM. The elevated ALT significantly correlated with MS and IFG/T2DM (i.e., 19.9-29.2% vs. 7.8% for MS, and 27.0-31.5% vs. 16.1% for IFG/T2DM). However, after excluding MS and adjustment for age and sex, the elevated ALT alone was not consistently associated with IFG/T2DM (36 < ALT ≤ 80 IU/L with OR 0.97, 95% CI 0.58-1.61; 80 < ALT ≤ 120 IU/L with OR 0.55, 95% CI 0.13-2.37; none with ALT > 120 had IFG).

Conclusions

In a cross-sectional analysis of Taiwanese industrial employees, elevated ALT associated with MS, but in subjects who did not meet MS criteria, elevated ALT by itself did not associate with IFG/T2DM.     

Components of the metabolic syndrome, but not the metabolic syndrome per se, are associated with aortic distensibility

Background and aimReduction in aortic distensibility occurs early in the atherosclerosis process and carries a poor prognosis. Metabolic syndrome is common and it is associated with increased cardiovascular mortality. The aim of this cross-sectional study was to investigate the association between metabolic syndrome and aortic distensibility.Methods and resultsA total of 135 subjects without diabetes were studied. Metabolic syndrome was diagnosed using the NCEP-ATP-III criteria. Aortic distensibility was assessed non-invasively by ultrasonography. Multivariate analysis, after controlling for the components of the metabolic syndrome, and, additionally, for body mass index, pulse pressure, presence of coronary artery disease, use of statins and use of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, demonstrated an independent association between aortic distensibility and age (p < 0.001), systolic blood pressure, (p = 0.02), diastolic blood pressure (p = 0.005), and history of hypertension (p < 0.001), but not metabolic syndrome status. Moreover, there was a suggestive association with albumin-to-creatinine ratio (p = 0.06).ConclusionsMetabolic syndrome per se is not associated with reduction in aortic distensibility. From the components of the metabolic syndrome, only blood pressure is a strong predictor of aortic distensibility. In addition, ageing and higher values of albumin-to-creatinine ratio are also associated with low aortic distensibility.     

Markers of endothelial activity are related to components of the metabolic syndrome, but not to circulating concentrations of the advanced glycation end-product N epsilon-carboxymethyl-lysine in healthy Swedish men

Endothelial function is considered important in the development of cardiovascular diseases and type 2 diabetes. Circulating advanced glycation end-products (AGEs) and dietary components have been shown to affect endothelial function in type 2 diabetics, but determinants of endothelial function in a non-diabetic population are more poorly investigated. Therefore, we investigated relationships between dietary habits, AGEs and endothelial activation in men with isolated metabolic disturbances. Circulating markers of endothelial activation (soluble forms of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and von Willebrand factor) and plasma N epsilon-carboxymethyl-lysine (CML, the predominant AGE in human plasma) were analyzed in a cross-sectional study of 294 healthy men. Individuals completed a 7-day dietary record, and metabolic and inflammatory parameters were determined. NCEP/ATPIII-criteria were used to define the metabolic syndrome. Endothelial activation was higher in individuals with the metabolic syndrome, and was positively related to certain features of the syndrome (insulin, glucose, inflammation and obesity), but not to others (triacylglycerol and blood pressure). Dietary factors were related to endothelial activation, but CML was not. Multivariate analysis revealed energy and alcohol intake, along with insulin and markers of oxidative stress and inflammation, to be positive predictors of endothelial activation. In this cohort of otherwise healthy men, endothelial activation was increased in individuals with the full metabolic syndrome, but not in those with only some of the components of the metabolic syndrome. Insulin resistance, inflammation, oxidative stress, the dietary intake of energy and alcohol, but not plasma CML, predicted endothelial activation in these men.     

Exercise lowers postprandial glucose but not fasting glucose in type 2 diabetes: a meta‐analysis of studies using continuous glucose monitoring

Exercise has repeatedly been shown to improve glycemic control as assessed by glycated hemoglobin. However, changes in glycated hemoglobin do not provide information regarding which aspects of glycemic control have been altered. The purpose of this systematic review was to examine the effect of exercise as assessed by continuous glucose monitoring systems (CGMS) in type 2 diabetes. Databases (PubMed, Medline, EMBASE) were searched up to February 2013. Eligible studies had participants with type 2 diabetes complete standardized exercise protocols and used CGMS to measure changes in glycemic control. Randomized controlled trials, crossover trials and studies with pre‐post designs were included. Average glucose concentration, daily time spent in hyperglycemia or hypoglycemia, and fasting glucose concentration were compared between exercise and control conditions. Eleven studies met the inclusion criteria and were included in the review. Eight studies had short‐term (≤2 weeks) exercise interventions, whereas three studies had a longer‐term intervention (all >2 months). The types of exercises utilized included aerobic, resistance and a combination of the two. The eight short‐term studies were included in quantitative analysis. Exercise significantly decreased average glucose concentrations (‐0.8 mmol/L, p < 0.01) and daily time spent in hyperglycemia (‐129 minutes, p < 0.01), but did not significantly affect daily time spent in hypoglycemia (‐3 minutes, p = 0.47) or fasting glucose (‐0.3 mmol/L, p = 0.13). The four randomized crossover trials had similar findings compared to studies with pre‐post designs. Exercise consistently reduced average glucose concentrations and time spent in hyperglycemia despite not significantly affecting outcomes such as fasting glucose and hypoglycemia. Copyright © 2013 John Wiley & Sons, Ltd.     

Combining protein and carbohydrate increases postprandial insulin levels but does not improve glucose response in patients with type 2 diabetes

ObjectiveA combined load of carbohydrate and protein stimulates insulin secretion. However, results on postprandial glucose responses in type 2 diabetic (T2D) subjects have been inconclusive. Therefore, we investigated the effects of co-ingestion of carbohydrate and protein on glucose and insulin responses in these subjects.MethodsAfter an overnight fast, 30 subjects consumed a drink containing 50 g of slowly-digested isomaltulose (ISO), combined either with a mixture of 21 g whey/soy (ISO + WS) or with 21 g casein (ISO + C) in a randomized order on separate days. In another experiment, the subjects consumed a control drink containing only 50 g ISO.ResultsNo significant differences in glucose responses were observed after ingestion of the drinks. Compared to ingestion of ISO alone, insulin response was ~ 190%–270% higher (P < .001), whereas insulin action was lower (P < .01) after ingestion of ISO + WS and ISO + C. Plasma insulin levels increased more significantly (P < .001) after ingestion of ISO + WS compared to ISO + C and were positively correlated with total amino acid levels (P < .001). Insulin action, however, showed a greater decrease following ingestion of ISO + WS than ISO + C (P < .01).ConclusionsCombining carbohydrate with protein can elevate postprandial insulin levels, but decreases insulin action, and therefore does not improve glucose response in T2D subjects. Our results further suggest that different types of proteins (i.e., fast-absorbing whey/soy vs. slow-absorbing casein) differently modulate insulin response and insulin action. A fast-absorbing protein mixture reduces insulin action to a greater extent than a slow-absorbing protein, and therefore may not be recommended for glycemic control in T2D patients.     

Physical activity reduces circulating TNF-alpha but not pro-thrombotic factors levels in patients with metabolic syndrome

AimsThe metabolic syndrome (MS) creates a pro-inflammatory state. Some cytokines increase their levels in patients with MS, among them tumor necrosis factor-alpha (TNF-alpha). On the other hand, MS is associated with a pro-thrombotic state in which increased levels of fibrinogen and plasminogen activator inhibitor type-1 (PAI-1) have been described.We tested the hypothesis that an intervention based on physical activity in adults with MS would reduce TNF-alpha, and the thrombogenic factors fibrinogen and PAI-1.Materials and MethodsWe studied 51 non-smoking subjects, both genders, between 39 and 62 years old. All of them presented MS and were randomly separated into two groups: Intervened-MS group (I-MS, n = 27), who participated in an 18-week intervention based on exercise and dietary counseling, and non-intervened MS group (NI-MS, n = 24), as control. Biochemical and anthropometric parameters were determined at baseline and at final time (18 weeks).ResultsThe intervention decreased the TNF-alpha serum levels (expressed as median and interquartile range IQR) from basal 3.6 (IQR = 2.1) to a final level of 1.7 (IQR = 1.8) pg/ml, in comparison to the NI-MS group: basal 4.0 (IQR = 1.8) to final 4.7 (IQR = 10.5) pg/ml (p < 0.0001). On the contrary, this treatment did not produce changes in the pro-thrombotic factors fibrinogen and PAI-1, although variations in PAI-1 were associated with changes in waist circumference (p = 0.026) and high-density lipoprotein cholesterol (p = 0.04).ConclusionOur results suggest that a non-pharmacological intervention program based on physical exercise is effective in reducing TNF-alpha levels in patients with MS, but had no effect regarding the levels of the pro-thrombotic factors PAI-1 and fibrinogen.     

A whole-grain cereal-based diet lowers postprandial plasma insulin and triglyceride levels in individuals with metabolic syndrome

Background and aimUntil recently, very few intervention studies have investigated the effects of whole-grain cereals on postprandial glucose, insulin and lipid metabolism, and the existing studies have provided mixed results. The objective of this study was to evaluate the effects of a 12-week intervention with either a whole-grain-based or a refined cereal-based diet on postprandial glucose, insulin and lipid metabolism in individuals with metabolic syndrome.Methods and resultsSixty-one men and women age range 40–65 years, with the metabolic syndrome were recruited to participate in this study using a parallel group design. After a 4-week run-in period, participants were randomly assigned to a 12-week diet based on whole-grain products (whole-grain group) or refined cereal products (control group). Blood samples were taken at the beginning and end of the intervention, both fasting and 3 h after a lunch, to measure biochemical parameters. Generalized linear model (GLM) was used for between-group comparisons. Overall, 26 participants in the control group and 28 in the whole-grain group completed the dietary intervention. Drop-outs (five in the control and two in the whole-grain group) did not affect randomization. After 12 weeks, postprandial insulin and triglyceride responses (evaluated as average change 2 and 3 h after the meal, respectively) decreased by 29% and 43%, respectively, in the whole-grain group compared to the run-in period. Postprandial insulin and triglyceride responses were significantly lower at the end of the intervention in the whole-grain group compared to the control group (p = 0.04 and p = 0.05; respectively) whereas there was no change in postprandial response of glucose and other parameters evaluated.ConclusionsA twelve week whole-grain cereal-based diet, compared to refined cereals, reduced postprandial insulin and triglycerides responses. This finding may have implications for type 2 diabetes risk and cardiovascular disease.     

老年男性血清睾酮与代谢综合征的关系

目的 探讨老年男性中血清睾酮与代谢综合征的关系。方法 研究对象为48例老年男性,测定身高、体重、体质指数、腰围、血糖、血胰岛素、血脂,用放射免疫法测定血清睾酮浓度,并用稳态公式（HOMA）计算胰岛素抵抗（HOMA-IR）,采用2001年美国国家胆固醇教育计划成人治疗小组（NCEP-ATPⅢ）提出的诊断标准进行分组,分析血清睾酮与代谢综合征的关系。结果 在老年男性中,有代谢综合征者睾酮浓度水平低于无代谢综合征者（P〈0.05）,通过调整年龄、吸烟、饮酒、体力活动后,睾酮浓度与代谢综合征发生显著负相关（P〈0.01）。结论 老年男性血清睾酮浓度与代谢综合征的发生密切相关,低睾酮水平是代谢综合征发生的重要参考标志之一。     

Association of metabolic syndrome with testosterone and inflammation in men

ObjectiveThere is limited data on the assessment of relationship between sex hormones, metabolic syndrome (MS) and inflammation. Therefore, our objective was to examine the relationship between metabolic syndrome, testosterone and inflammation.Patients and methodsIt was a cross-sectional study which included 309 subjects in the age range of 30–70 years. Blood was analyzed for plasma glucose, serum lipids, total testosterone (TT) and high-sensitivity C-reactive protein (hs-CRP).ResultsThere were 153 patients with metabolic syndrome and 156 without MS according to modified NCEP guidelines. Age, BMI, obesity, dyslipidaemia, smoking (OR = 2.35, CI = 1.35–4.09), LDL-Ch, low TT (OR = 0.76, CI = 0.38–1.52) and elevated hs-CRP (OR = 1.56, CI = 0.87–2.80) were significant independent predictors of MS (all P < 0.05).ConclusionsThe low testosterone and high hs-CRP levels are independent predictors of metabolic syndrome.