Epidemiology of metabolic syndrome

Metabolic syndrome (MetS), also previously known by a variety of other names, including insulin resistance syndrome and the deadly quartet, is characterized by clustering of abdominal (visceral and retroperitoneal) obesity and other cardiovascular risk factors, including impaired glucose regulation, raised triglycerides, decreased high-density lipoprotein cholesterol (HDL-C), elevated blood pressure (BP).

Associated with increased risk of both type 2 diabetes and cardiovascular disease (CVD), MetS is believed to be a contributor to the modern-day epidemics of diabetes and CVD and has become a major public health challenge around the world [I]. Currently, there are five different sets of criteria which have been developed to characterize the syndrome. These definitions differ in the components included and the cut-points used for each component. The prevalence of MetS in the westernized world is significant (10-50%) and believed to be increasing over time. The pathophysiology of the syndrome is unclear, but it is thought that obesity and/or insulin resistance are key underlying components. Genetics, lifestyle and environment factors are also important causes of MetS.

This chapter provides:

• a historical overview of the evolution of MetS;
• a summary of the value of the different definitions used to characterize the syndrome;
• a summary of the underlying pathophysiology, the causes and other important risk factors of MetS;
• a summary of the evidence describing the association of MetS with CVD and diabetes;
• a summary of the prevalence of MetS using the various definitions in different countries.

Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet

The mechanisms of how tea and epigallocatechin-3-gallate (EGCG) lower body fat are not completely understood. This study investigated long-term administration of green tea (GT), black tea (BT), or isolated EGCG (1 mg/kg per day) on body composition, glucose tolerance, and gene expression related to energy metabolism and lipid homeostasis; it was hypothesized that all treatments would improve the indicators of metabolic syndrome. Rats were fed a 15% fat diet for 6 months from 4 weeks of age and were supplied GT, BT, EGCG, or water. GT and BT reduced body fat, whereas GT and EGCG increased lean mass. At 16 weeks GT, BT, and EGCG improved glucose tolerance. In the liver, GT and BT increased the expression of genes involved in fatty acid synthesis (SREBP-1c, FAS, MCD, ACC) and oxidation (PPAR-α, CPT-1, ACO); however, EGCG had no effect. In perirenal fat, genes that mediate adipocyte differentiation were suppressed by GT (Pref-1, C/EBP-β, and PPAR-γ) and BT (C/EBP-β), while decreasing LPL, HSL, and UCP-2 expression; EGCG increased expression of UCP-2 and PPAR-γ genes. Liver triacylglycerol content was unchanged. The results suggest that GT and BT suppressed adipocyte differentiation and fatty acid uptake into adipose tissue, while increasing fat synthesis and oxidation by the liver, without inducing hepatic fat accumulation. In contrast, EGCG increased markers of thermogenesis and differentiation in adipose tissue, while having no effect on liver or muscle tissues at this dose. These results show novel and separate mechanisms by which tea and EGCG may improve glucose tolerance and support a role for these compounds in obesity prevention.

Effect of carbohydrate ingestion on exercise-induced alterations in metabolic gene expression

Skeletal muscle possesses a high degree of plasticity and can adapt to both the physical and metabolic challenges that it faces. An acute bout of exercise is sufficient to induce the expression of a variety of metabolic genes, such as GLUT4, pyruvate dehydrogenase kinase 4 (PDK-4), uncoupling protein-3 (UCP3), and peroxisome proliferator-activated receptor-? coactivator 1 (PGC-1). Reducing muscle glycogen levels before exercise potentiates the effect of exercise on many genes. Similarly, altered substrate availability induces transcription of many of these genes. The purpose of this study was to determine whether glucose ingestion attenuates the exercise-induced increase in a variety of exercise-responsive genes. Six male subjects (28 ± 7 yr; 83 ± 3 kg; peak pulmonary oxygen uptake = 46 ± 6 ml·kg–1·min–1) performed 60 min of cycling at 74 ± 2% of peak pulmonary oxygen uptake on two separate occasions. On one occasion, subjects ingested a 6% carbohydrate drink. On the other occasion, subjects ingested an equal volume of a sweet placebo. Muscle samples were obtained from vastus lateralis at rest, immediately after exercise, and 3 h after exercise. PDK-4, UCP3, PGC-1, and GLUT4 mRNA levels were measured on these samples using real-time RT-PCR. Glucose ingestion attenuated (P < 0.05) the exercise-induced increase in PDK-4 and UCP3 mRNA. A similar trend (P = 0.09) was observed for GLUT4 mRNA. In contrast, PGC-1 mRNA increased following exercise to the same extent in both conditions. These data suggest that glucose availability can modulate the effect of exercise on metabolic gene expression.

Effect of low and high glycaemic index diets on developing the risk of metabolic syndrome in rats

Several observational studies have shown that the chronic consumption of high glycaemic index diet is associated with an increased risk of developing metabolic syndrome.  This study was performed to identify the direct influences on the lipid profile and the adipose tissue deposition and the subsequent development of the risk of metabolic syndrome in rats by feeding diets of low glycaemic index (LGI) and high glycaemic index (HGI). Fifty rat weanlings (three weeks old) were equally divided into two groups and fed on either low glycaemic index diet based on high amylose, or isocaloric high glycacmic index diet for 12 weeks. Postprandial blood and tissue samples were collected at the end of the 12 weeks of feeding. The total white adipose tissue weights of the HGl fed rats (24.74 ± 0.53 glrat) were significantly higher than the LGl fed rats (15.37 ± 0.36 gh·at). The HO! led rats had higher postprandial leptin concentrations (1.86 ± 0.17 ng/ml) than LGI fed rats (1.34 ± 0.12 ng/ml). The postprandial insulin, and postprandial insulin glucose ratio were higher in the HGI fed rats (7.06 ± 0.90 ng/ml and 0.67 ± 0.01 ng/mlxmM) compared to the LGl fed rats (3.91 ± 0.4 ng/ml and 0.44 ± 0.01 ng/mlxmM). Triglycerides of the l-IGI fed rats showed higher values (I .56 ± 0.10 mM) than the LO! fed rats (l.07 ± 0.08 mM). The results indicated that LGI feeding was beneficial in preventing the conditions enhancing the cardio vascular disease whereas long-term feeding of HGI diet may increase the risk of developing metabolic syndrome in rats.

Relationship of nutritional and metabolic factors to non-invasive indices of macrovascular disease in diabetes

Factors which may account for the high frequency of macrovascular disease in diabetics are age, sex, cigarette smoking, hypertension, obesity, lack of exercise, diet, hyperglycaemia, hyperinsulinaeroia, hypercholesterolaemia, hypertriglyceridaemia, low HDL-cholesterol concentration, elevated free fatty acid concentration and enhanced platelet aggregation. Twenty seven (13 men and 14 women) non-insulin-dependent diabetics and thirty eight age, height and weight matched healthy subjects (10 men and 28 women) were studied. None of the subjects were smokers, or hypertensive. No subject had any clinical evidence of peripheral arterial disease, coronary heart disease or cerebrovascular disease. All had apparently normal peripheral pulses and normal ankle/arm blood pressure indices. Methods for determining arterial compliance in the segment between the left subclavian artery and each common femoral artery, and proximal resistance at the common femoral artery and posterior tibial artery, have been reviewed and developed. An appropriate food intake methodology for deriving food indices from food records was developed. Biochemical determinants have been made of glucose tolerance, glycosylated haemoglobin, serum total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride, plasma free fatty acid and insulin. A significant decrease in the arterial compliance, and a significant increase in the arterial proximal resistance at the common femoral artery and posterior tibial artery in non-insulin-dependent diabetics, compared with their healthy controls, have been found. Significant negative correlation between arterial compliance and proximal resistance and, a significant positive correlation between the arterial proximal resistance of common femoral artery and posterior tibial artery were found. Differences between control (healthy subjects) and non-insulin-dependent diabetic groups indicate that preclinical peripheral arterial disease can be recognised even in mild diabetics by non-invasive measurement of arterial compliance or proximal resistance. There were significant and negative correlations between arterial compliance and each of blood glucose, blood glycosylated haemoglobin (HbAlC), plasma free fatty acid and plasma insulin concentration. There were significant and positive correlations between arterial proximal resistance of common femoral artery and posterior tibial artery and each of blood glucose, glycosylated haemoglobin and plasma free fatty acid concentration. Multivariate analysis to examine each of the biochemical factors Including blood glucose, blood glycosylated haemoglobin (HbAlC), plasma free fatty acid, plasma Insulin and lipids, showed that the factor which most influenced the arterial compliance and the proximal resistance of posterior tibial artery was the glucose level in the fasting state or the glucose response after a glucose load. In addition, the factors which most influenced proximal resistance of the common femoral artery were free fatty acid -level in the fasting state or glucose response after a glucose load. The factors which most influenced arterial compliance were glucose level in men, and the insulin level in the fasting state or the plasma free fatty acid response after a glucose load in women. These findings indicate that blood glucose, plasma free fatty acid and plasma insulin are risk factors for changes in arterial wall characteristic at a stage when no clinical evidence of macrovascular disease is apparent. Arterial compliance was decreased and the proximal resistance of posterior tibial artery was increased in those with a low intake of protective foods compared with those with a high intake whether healthy subjects or non-insulin-dependent diabetics. Arterial compliance was decreased in non-fish eaters compared with the fish eaters whether healthy subjects or non-insulin-dependent diabetics. Proximal resistance of the posterior tibia! artery in non-fish eaters was increased compared with fish eaters in healthy subjects. Overall, food variety, a protective food score consumption and fish consumption emerge as importance determinants of arterial wall characteristics at a stage when no clinical evidence of macrovascular disease is apparent.

Higher leptin levels in Asian Indians than Creoles and Europids : a potential explanation for increased metabolic risk

Background and purpose: Leptin predicts cardiovascular diseases and type 2 diabetes, diseases to which Asian Indians are highly susceptible. As a risk marker, leptin’s intra-individual and seasonal stability is unstudied and only small studies have compared leptin levels in Asian Indians with other populations. The aim of this study was to explore ethnicity related differences in leptin levels and its intra-individual and seasonal stability.

Methods: Leptin and anthropometric data from the northern Sweden MONICA (3513 Europids) and the Mauritius Non-communicable Disease (2480 Asian Indians and Creoles) studies were used. In both studies men and women, 25- to 74-year old, participated in both an initial population survey and a follow-up after 5–13 years. For the analysis of seasonal leptin variation, a subset of 1780 participants, 30- to 60-year old, in the Vasterbotten Intervention Project was used.

Results: Asian Indian men and women had higher levels of leptin, leptin per body mass index (BMI) unit (leptin/BMI) or per cm in waist circumference (WC; leptin/waist) than Creoles and Europids when adjusted for BMI (all P<0.0005) or WC (all P<0.005). In men, Creoles had higher leptin, leptin/BMI and leptin/waist than Europids when adjusted for BMI or WC (all P<0.0005). In women, Creoles had higher leptin/BMI and leptin/waist than Europids only when adjusted for WC (P<0.0005). Asian Indian ethnicity in both sexes, and Creole ethnicity in men, was independently associated with high leptin levels. The intra-class correlation for leptin was similar (0.6–0.7), independently of sex, ethnicity or follow-up time. No seasonal variation in leptin levels was seen.

Conclusion: Asian Indians have higher levels of leptin, leptin/BMI and leptin/waist than Creoles and Europids. Leptin has a high intra-individual stability and seasonal leptin variation does not appear to explain the ethnic differences observed here.

Profiling the sport consumption attitudes and behaviours of fantasy football players

Most sporting codes encourage participation in Fantasy Sport (FS), despite few making direct revenue from it. There is a lack of empirical evidence whether this is good practice, for although FS can increase involvement and education, it may also compete with other forms of sport consumption for consumers limited resources. This study begins to address whether FS competes with or  complements sport consumption by comparing FS players with nonplayers. Data was collected from surveys (n=182) of AFL fans, with findings indicating FS players had higher tested measures of attitudes (e.g., team identification, commitment) and behaviours (e.g., game attendance, television viewing) related  to the sport. What remains to be determined is causality, and suggestions on how to examine this are given.

The association of levels of physical activity with metabolic syndrome in rural Australian adults

Background:  Physical activity (PA) reduces risk factors related to metabolic syndrome. Rurality influences the way people incorporate physical activity into daily life. The aim of this study is to determine the association of PA level with metabolic syndrome in a rural Australian population. The influence of adiposity on these associations is also investigated.

Methods: Three cross-sectional population health surveys were conducted in south-east Australia during 2004–2006 using a random population sample (n = 1563, participation rate 49%) aged 25–74 years. PA was assessed via a self-administered questionnaire, and components of the metabolic syndrome via anthropometric measurements taken by specially trained nurses and laboratory tests.

Results: Approximately one-fifth of participants were inactive in leisure-time and over one-third had metabolic syndrome (men 39%, women 33%; p = 0.022). There was an inverse association between level of PA and metabolic syndrome (p < 0.001). Men who were inactive in leisure-time were more than twice as likely and women more than three times as likely to have metabolic syndrome compared with those having high PA. Body mass index (BMI) is a mediating factor in the association between level of PA and metabolic syndrome.

Conclusion: Some PA is better than none if adults, particularly women, are to reduce their risk of metabolic syndrome and associated vascular diseases. Specialised interventions that take rurality into consideration are recommended for adults who are inactive.

Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans

Low-volume ‘sprint’ interval training (SIT) stimulates rapid improvements in muscle oxidative capacity that are comparable to levels reached following traditional endurance training (ET) but no study has examined metabolic adaptations during exercise after these different training strategies. We hypothesized that SIT and ET would induce similar adaptations in markers of skeletal muscle carbohydrate (CHO) and lipid metabolism and metabolic control during exercise despite large differences in training volume and time commitment. Active but untrained subjects (23 ± 1 years) performed a constant-load cycling challenge (1 h at 65% of peak oxygen uptake before and after 6 weeks of either SIT or ET (n = 5 men and 5 women per group). SIT consisted of four to six repeats of a 30 s ‘all out’ Wingate Test (mean power output ∼500 W) with 4.5 min recovery between repeats, 3 days per week. ET consisted of 40–60 min of continuous cycling at a workload that elicited ∼65% (mean power output ∼150 W) per day, 5 days per week. Weekly time commitment (∼1.5 versus ∼4.5 h) and total training volume (∼225 versus ∼2250 kJ week−1) were substantially lower in SIT versus ET. Despite these differences, both protocols induced similar increases (P < 0.05) in mitochondrial markers for skeletal muscle CHO (pyruvate dehydrogenase E1α protein content) and lipid oxidation (3-hydroxyacyl CoA dehydrogenase maximal activity) and protein content of peroxisome proliferator-activated receptor-γ coactivator-1α. Glycogen and phosphocreatine utilization during exercise were reduced after training, and calculated rates of whole-body CHO and lipid oxidation were decreased and increased, respectively, with no differences between groups (all main effects, P < 0.05). Given the markedly lower training volume in the SIT group, these data suggest that high-intensity interval training is a time-efficient strategy to increase skeletal muscle oxidative capacity and induce specific metabolic adaptations during exercise that are comparable to traditional ET.

Metabolic adaptations to short-term high-intensity interval training : a little pain for a lot of gain?

High-intensity interval training (HIT) is a potent time-efficient strategy to induce numerous metabolic adaptations usually associated with traditional endurance training. As little as six sessions of HIT over 2 wk or a total of only approximately 15 min of very intense exercise (~600 kJ), can increase skeletal muscle oxidative capacity and endurance performance and alter metabolic control during aerobic-based exercise.

Histone modifications and skeletal muscle metabolic gene expression

1.      Skeletal muscle oxidative function and metabolic gene expression are co-ordinately downregulated in metabolic diseases such as insulin resistance, obesity and Type 2 diabetes. Altering skeletal muscle metabolic gene expression to favour enhanced energy expenditure is considered a potential therapy to combat these diseases.

2.      Histone deacetylases (HDACs) are chromatin-remodelling enzymes that repress gene expression. It has been shown that HDAC4 and 5 co-operatively regulate a number of genes involved in various aspects of metabolism. Understanding how HDACs are regulated provides insights into the mechanisms regulating skeletal muscle metabolic gene expression.

3.      Multiple kinases control phosphorylation-dependent nuclear export of HDACs, rendering them unable to repress transcription. We have found a major role for the AMP-activated protein kinase (AMPK) in response to energetic stress, yet metabolic gene expression is maintained in the absence of AMPK activity. Preliminary evidence suggests a potential role for protein kinase D, also a Class IIa HDAC kinase, in this response.

4.      The HDACs are also regulated by ubiquitin-mediated proteasomal degradation, although the exact mediators of this process have not been identified.

5.      Because HDACs appear to be critical regulators of skeletal muscle metabolic gene expression, HDAC inhibition could be an effective therapy to treat metabolic diseases.

6.      Together, these data show that HDAC4 and 5 are critical regulators of metabolic gene expression and that understanding their regulation could provide a number of points of intervention for therapies designed to treat metabolic diseases, such as insulin resistance, obesity and Type 2 diabetes.