Related Cardiometabolic Complications Research Articles

Lifestyle-based subtypes of childhood obesity and their association with cardiometabolic factors: A cluster analysis.

Lifestyle factors play an important role in the development and management of childhood obesity and its related cardiometabolic complications. We aimed to explore childhood obesity subtypes based on lifestyle factors and examine their association with cardiometabolic health. We included 1550 children with obesity from the National Health and Nutrition Examination Survey. Cluster analysis identified obesity subtypes based on four lifestyle factors (physical activity, diet quality, sedentary time and smoking). Multiple linear regression assessed their association with cardiometabolic factors. Five subtypes of childhood obesity were identified: unhealthy subtype (n = 571; 36.8%), physically active subtype (n = 185; 21.1%), healthy diet subtype (n = 404; 26.1%), smoking subtype (n = 125; 8.1%) and non-sedentary subtype (n = 265; 17.1%). Compared with the unhealthy subtype, the physically active subtype had lower insulin and HOMA-IR levels, and smoking subtype was associated with lower HDL levels. When compared with children with normal weight, all obesity subtypes had worse cardiometabolic profile, except the physically active subtype who had similar DBP, HbA1c and TC levels; smoking subtype who had similar TC levels; and healthy diet and non-sedentary subtypes who had similar DBP levels. Children of different lifestyle-based obesity subtypes might have different cardiometabolic risks. Our new classification system might help personalize assessment of childhood obesity.

Early detection of childhood overweight and related complications in a Danish population-based cohort aged 2–8 years

BackgroundOverweight in early childhood often tracks into adolescence and adulthood and early childhood is a critical period for developing sustained overweight. This study aims to investigate the early detection of childhood overweight (including obesity) and related cardiometabolic complications in a Danish population-based cohort of children aged 2.5–8 years in collaboration with primary care municipal dental clinics and public health nurses. MethodsIn this prospective population-based cohort study, 335 pre-school children (age 2.5 and 5 years) were recruited from municipal dental clinics, and 657 school children (age 6–8 years) by public health nurses. A subgroup of 392 children (40%) participated in additional hospital-based examinations including blood pressure measurement and a blood sample. Children were re-examined approximately one year later. ResultsThe prevalence of overweight was 13.73% in pre-school children and 13.69% in school children at baseline. In the pre-school children, differences in cardiometabolic risk markers between children with and without overweight were minor, whereas in school children with overweight, cardiometabolic derangements were manifest including significantly higher levels of fasting glucose, insulin, homoeostasis model of assessment for insulin resistance, triglycerides, and alanine aminotransferase and lower levels of high-density lipoprotein cholesterol. During follow-up the prevalence of overweight did not change in pre-school children but increased to 17.0% in school children. ConclusionsExisting contacts with the primary health care sector, including dental care, can successfully be used for detection of overweight. This study suggests that early detection should be initiated at pre-school ages since overweight-related complications are already established by school ages.

Indicators of Obesity and Cardio-metabolic Risks: Important Consideration in Adults and Children.

The prevalence of obesity has dramatically increased all over the world. Body mass index (BMI) has been used as the most common available measure to determining obesity status. While the site of excessive fat mass accumulation is a stronger determinant of cardio-metabolic complication, with respect to systemic and generalized obesity, which is only determined through BMI. So, it is concluded that using traditional anthropometric indices such as BMI for interpreting the obesity status and cardio-metabolic risk has considerable limitations. Thus, the main aims of the present study are to discuss possible drawbacks of anthropometric indices especially BMI, which in epidemiological studies are usually neglected, as well as lend important consideration to using other anthropometric indices such as measurement of obesity and related cardio-metabolic complications with a special emphasis on the use of waist circumference, waist-to-hip ratio and waist-to-height ratio.

Abstract MP90: Identifying Risk Profiles for Sedentary Behavior in Youth Using Recursive Partitioning Based on Individual, Familial, and Neighborhood Environment Factors

Background: Being sedentary is an established risk factor for obesity and related cardiometabolic complications, independently of physical activity (PA) levels. We used recursive partitioning analysis (RPA) to identify unique combinations of individual, familial, and neighborhood factors that increased the likelihood of being very sedentary. Methods: Baseline data were collected in 2005-2008 for 512 Quebec youth (aged 8-10 years) with a history of parental obesity (QUALITY study). Sedentary behavior and PA were assessed by accelerometry (Actigraph). Children with ≥10h of valid wear time on at least 4 days were retained for analysis. Children were categorized as being very sedentary if they accumulated at least 300 minutes/day of ≤100 counts/min on average. Fifteen variables were submitted to the recursive partitioning process in order to identify sub-groups by likelihood of being very sedentary. MLR was used to estimate likelihood of being very sedentary across subgroups, controlling for the child’s age, sex, household income, and PA level. Indicator variables were used, retaining the lowest risk group as the reference. Results: Data were complete for 445/512 participants. Six variables were retained to construct the classification tree. A total of 7 subgroups were identified, with proportions very sedentary equal to 5%, 22%, 31%, 26%, 33%, 40%, and 77%, respectively. The 7 risk subgroups, in order of increasing likelihood of being very sedentary, comprised children who: (1) met MVPA guidelines (engaged in at least 60 min/day of MVPA), (2) did not meet MVPA guidelines, but resided in lower poverty areas, (3) did not meet MVPA guidelines, resided in higher poverty areas, but with a higher park area ratio; (4) did not meet MVPA guidelines, resided in higher poverty areas, had a lower park area ratio, but did not have an obese father; (5) did not meet MVPA guidelines, resided in higher poverty areas, had a lower park area ratio, had an obese father, but lived in more urban areas; (6) same as subgroup (5) but living in less urban areas and not exceeding 2 hours/day of screentime on weekends; and finally (7) same as subgroup (6) but exceeding 2 hours per day of screentime on weekends. In multivariable logistic regressions, compared to subgroup 1, groups 2 to 7 were significantly more likely to be very sedentary, after controlling for age, sex and household income. However, after further controlling for minutes of MVPA, only children in group 7 remained significantly more likely to be categorized as very sedentary (OR: 7.3, 95% CI: 1.3-45.1). Conclusion: The relationship between physical activity and sedentary behaviour is complex. Specific combinations of factors appear particularly conducive to engaging in excessive sedentary behaviour, with weekend screen time possibly being the most salient individual contributor.

Essential roles of four-carbon backbone chemicals in the control of metabolism.

The increasing incidence of obesity worldwide and its related cardiometabolic complications is an urgent public health problem. While weight gain results from a negative balance between the energy expenditure and calorie intake, recent research has demonstrated that several small organic molecules containing a four-carbon backbone can modulate this balance by favoring energy expenditure, and alleviating endoplasmic reticulum stress and oxidative stress. Such small molecules include the bacterially produced short chain fatty acid butyric acid, its chemically produced derivative 4-phenylbutyric acid, the main ketone body D-β-hydroxybutyrate - synthesized by the liver - and the recently discovered myokine β-aminoisobutyric acid. Conversely, another butyrate-related molecule, α-hydroxybutyrate, has been found to be an early predictor of insulin resistance and glucose intolerance. In this minireview, we summarize recent advances in the understanding of the mechanism of action of these molecules, and discuss their use as therapeutics to improve metabolic homeostasis or their detection as early biomarkers of incipient insulin resistance.

The Heme Oxygenase System and Type-1 Diabetes

Diabetes is a complex endocrine/metabolic disease with many related complications including micro-vascular and macrovascular problems such as cardiomyopathy, nephropathy, neuropathy and retinopathy. Generally, type-1 diabetes is caused by autoimmune- mediated destruction of pancreatic beta cells leading to insulin deficiency. This is usually accompanied by dyslipidemia, enhanced hyperglycemia-mediated oxidative stress, endothelial-cell dysfunction and apoptosis. For decades, type-1 diabetes has been traditionally known as insulin-dependent, while type-2 as non-insulin dependent diabetes. However, it is becoming increasingly clear that insulin deficiency and insulin resistance are manifested in both forms of diabetes at different stages. Thus, it may be time revisit the nomenclature and adjust it to reflect these observations of insulin deficiency and insulin resistance in both forms of diabetes to avoid ambiguity when discussing forms of diabetes. Emerging evidence indicates that the heme-oxygenase (HO) system and related products including carbon monoxide, ferritin and biliverdin are capable of suppressing immune/inflammatory response, and abate oxidative stress and apoptosis. More importantly, upregulating the HO-system increases pancreatic beta-cell insulin release and reduce hyperglycemia in different diabetic models. Similarly, carbon monoxide, a product of the HO-catalyzed degradation of heme also enhances insulin production and improves glucose metabolism. Since excessive immune/inflammatory responses coupled to elevated apoptosis are among the cardinal pathophysiological features of type-1 diabetes, this review highlights the role of the HO-system and related products such as carbon monoxide and bilirubin in the modulation of apoptosis and immune response, and the beneficial effects of the HO-system in the pathogenesis of type-1 diabetes and related cardiometabolic complications.

A Critical and Comprehensive Insight on Heme Oxygenase and Related Products Including Carbon Monoxide, Bilirubin, Biliverdin and Ferritin in Type-1 and Type-2 Diabetes

The increased prevalence of diabetes and associated complications presents a major health risk worldwide, and requires an efficient management protocol. Type-1 and type-2 diabetes have several common pathophysiological denominators including hyperglycemia, elevated oxidative stress, increased inflammation and apoptosis. These pathological factors are implicated in the progression and worsening of the disease, and the related cardiometabolic complications associated with it. Despite the advancement in management of type-1 and type-2 diabetes, the high incidence of diabetes and related complications calls for novel therapeutic strategies. Recent findings suggest that the pharmacological modulation of the microsomal heme oxygenase (HO) system may be an important therapeutic avenue to explore. The HO system and related products such as carbon monoxide, bilirubin, biliverdin, biliverdin reductase and ferritin have been shown to abate inflammation, oxidative stress, and apoptosis and reduce hyperglycemia. In addition, the HO system also enhances insulin sensitivity and increase pancreatic beta cell insulin production in experimental models of type-1 and type-2 diabetes. This review is an effort to provide evidence of the regulatory and cytoprotective role of the HO system in type-1 and type-2 diabetes, and will highlight the multifaceted mechanisms implicated in the anti-diabetic effects of the HO system.

Circulating Adipokines in Healthy versus Unhealthy Overweight and Obese Subjects

It is now well established that not all obese subjects are at increased risk of cardiometabolic complications; such patients are termed the metabolically healthy obese. Despite their higher-than-normal body fat mass, they are still insulin sensitive, with a favorable inflammatory and lipid profile and no signs of hypertension. It remains unclear which factors determine an individual's metabolic health. Adipose tissue is known to secrete multiple bioactive substances, called adipokines, that can contribute to the development of obesity-associated complications. The goal of this study was to determine whether the circulating adipokine profiles differs between metabolically healthy and metabolically unhealthy overweight and obese subjects, thereby obtaining data that could help to explain the link between obesity and its related cardiometabolic complications. We defined metabolic health in terms of several metabolic and inflammatory risk factors. The serum adiponectin levels were higher in the healthy group and showed a positive correlation with HDL cholesterol levels in the unhealthy group. There were no differences between the two groups in the levels of serum leptin, chemerin and orosomucoid. Accordingly, adiponectin might play a role in protecting against obesity-associated cardiometabolic derangements. More studies are needed to clarify the role of different chemerin isoforms in this system.

Implications of estrogen receptor alpha and estrogen receptor beta for adipose tissue functions and cardiometabolic complications.

There is growing evidence that estrogen signaling regulates energy metabolism and exerts important functions in maintaining adipose tissue metabolism, including controlling the distribution of body fat. Changes in the physiological functions of adipose tissue, particularly the white adipose tissue, have been strongly connected to obesity and the development of related cardiometabolic complications. In this review, we will focus on discussing the role of estrogen signaling in regulating adipocyte differentiation, metabolism and its endocrine function with a focus on the possible underlying molecular mechanisms mediated by estrogen receptor α and estrogen receptor β.

Body Fat Distribution and Insulin Resistance

The burden of obesity has increased globally over the last few decades and its association with insulin resistance and related cardio-metabolic problems have adversely affected our ability to reduce population morbidity and mortality. Traditionally, adipose tissue in the visceral fat depot has been considered a major culprit in the development of insulin resistance. However, there is a growing body of evidence supporting the role of subcutaneous truncal/abdominal adipose tissue in the development of insulin resistance. There are significant differences in the functional characteristics of subcutaneous abdominal/truncal vs. intraabdominal vs. gluteo-femoral fat depots. More recently, mounting evidence has been supporting the role of adipose tissue function in the development of metabolic complications independent of adipose tissue volume or distribution. Decreased capacity for adipocyte differentiation and angiogenesis along with adipocyte hypertrophy can trigger a vicious cycle of inflammation leading to subcutaneous adipose tissue dysfunction and ectopic fat deposition. Therapeutic lifestyle change continues to be the most important intervention in clinical practice to improve adipose tissue function and avoid development of insulin resistance and related cardio-metabolic complications.

Stress hormones: physiological stress and regulation of metabolism

Stress, defined as a state of threatened homeostasis, mobilizes a complex spectrum of adaptive physiologic and behavioral responses that aim to re-establish the challenged body homeostasis. The hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) constitute the main effector pathways of the stress system, mediating its adaptive functions. In western societies, indices of stress correlate with increasing rates of both obesity and metabolic syndrome which have reached epidemic proportions. Recent data indicate that chronic stress, associated with mild hypercortisolemia and prolonged SNS activation, favors accumulation of visceral fat and contributes to the clinical presentation of visceral obesity, type 2 diabetes, and related cardiometabolic complications. Reciprocally, obesity promotes a systemic low-grade inflammation state, mediated by increased adipokine secretion, which can chronically stimulate the stress system.