MetS or Metabolic syndrome is a mounting health problem. Its prevalence parallels the rising trends in childhood obesity rates. MetS is a constellation of obesity with metabolic abnormalities that are by themselves a cluster of cardiovascular risk factors (hypertension, insulin resistance, impaired glucose tolerance, dyslipidemia). Although frequently discussed in literature, MetS is a “difficult-to-define” adverse biochemical phenotype due to its fragmentary classification, racial/pubertal differences and lack of cardiovascular events in children, environmental factors and incomplete understanding of its pathogenesis. Besides cardiovascular risk and type2DM, MetS is also associated with oxidative stress, chronic inflammation, hepatic steatosis, non-alcoholic fatty liver disease, obstructive sleep apnea, hypogonadism, hyperandrogenism and polycystic ovary. Given its protean implications, it is imperative for us to understand its pathophysiology, risk factors and to identify schema for management of metabolic syndrome in childhood.
Definition
Historically what began as a concept rather than a diagnosis by itself now has over 40 definitions in children and adolescents. From Kylin to Kaplan, MetS has been described using several names throughout the years. Reaven called it “Syndrome X” and Kaplan, “The deadly quartet” for the combination of upper body obesity, glucose intolerance, hypertriglyceridemia, and hypertension.
Although several attempts have been made to define diagnostic criteria for pediatric MetS, no consensus exists. This is because certain methodological and physiological limitations complicate the formulation of a lucid definition. For instance, children develop transient physiologic insulin resistance during puberty and normal lipid levels vary according to age, sex and ethnicity.
The first proposition of defining criteria was published in 2003. It was elaborated by assessing adolescents from 12 to 19 years using modified criteria, based on the criteria of NCEP/ATP-III, including abdominal circumference over 90th percentile, blood pressure over the limits established by the National Blood Pressure Education Program, lipids over the limits established by the National Cholesterol Education Program for children, and glycemia over the values for adults. The second proposal was similar to the first but for its lower cut off values. The third chose BMI as a marker, a variable that would be less dependent on race/ethnicity.
In 2007, the International Diabetes Federation (IDF) attempted a definition of pediatric metabolic syndrome using age-specific diagnostic criteria.
International Diabetes Federation (IDF) definition of metabolic syndrome in children
The more recent definition of paediatric MetS has been provided by the Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS) consortium in 2014, suggesting the use of percentiles for each diagnostic criterion.
Pathophysiology
A plausible interconnected loop encompassing 3 factors has been implicated in the pathophysiology of MetS.
- Insulin resistance
- Obesity
- Inflammation
Insulin resistance is the converse of insulin sensitivity. It is characterized by reduced tissue response to insulin mediated cellular activity. However not all insulin effects are impaired. For reasons unknown there is “selective or dissociated” insulin resistance. On one hand there is impaired insulin mediated glucose homeostasis. On the other hand, there is enhanced insulin mediated hepatic denovo lipogenesis causing the release of free fatty acids and triglycerides into the circulation. This results in dyslipidemia and visceral/ectopic adipose deposition which in turn triggers release of proinflammatory cytokines causing a state of low grade inflammation.
Concept of Lipid Partitioning
The metabolic impact of obesity is determined by the pattern of lipid partitioning i.e the distribution of body fat in various organs and compartments. Altered lipid-partitioning in the visceral compartment and insulin responsive tissues (muscle/liver) results in an adipocytokine flux. This in turn perpetuates endothelial dysfunction and insulin resistance. Also the visceral fat accumulation generates a plethora of intracellular reactive oxygen species, overwhelms antioxidant defences thereby causing cellular shutdown, flawed insulin production and Type2DM.
Risk factors
Obesity by itself is an independent risk factor in the development of Type2DM and CVD. Obesity is diagnosed based on body mass index (BMI) for gender and age.
BMI ≥95th percentile -Obese.
BMI of ≥85th percentile and <95th percentile – Overweight
Visceral adiposity, regardless of the degree of obesity, is robustly linked with both childhood metabolic syndrome and CVD later in life. Visceral adiposity can be estimated using waist circumference and waist to hip ratio. Waist to height ratio is also used in children in addition to the above. A value of 0.6 or more is indicative of increased risk.
Breastfeeding has been shown to lower the risk of MetS later on in life. Childhood metabolic syndrome bears reciprocity to gestational DM and large-for-date babies (Barker’s hypothesis). Heredity and family history of obesity/metabolic syndrome have also been recognized as significant factors. Lack of physical activity and outdoor play, fatty food consumption (junk food, empty calories), excessive screen time and gadgets use are lifestyle factors that increase risk considerably.
Screening
Screening criteria for metabolic syndrome (Indian Academy of Pediatrics (IAP) guidelines and WHO guidelines) and recommendations for laboratory workup are described below.
Prevention and Treatment
Lifestyle interventions
Provide a healthy diet that is balanced, wholesome, replete with fruits and vegetables, more fiber and less trans fat. Avoid carbonated drinks, refined carbohydrates, high fructose corn syrup, salty and processed food.
Dietary Approaches to Stop Hypertension (DASH) – Include a diet that is rich in fruits, vegetables, low-fat dairy, whole grains, fish, poultry, nuts, and lean meat and poor in sugar, sweets, and sodium for children and adolescents with risk factors.
Physical activity
Incorporate at least 20 min of vigorous short bursts of physical activity 1 day, 3 to 5 days per week.
Good physical activity, healthy sleep routines and screen time discretion result in a positive effect by reducing sedentary behaviour in children.
Pharmacological therapy
Drugs to treat hypertension, dyslipidemia and type2DM are initiated as appropriate. Pharmacotherapeutic options for obesity are limited and currently Orlistat is the only FDA approved drug over 12 years. Metformin however has been used off-label to treat childhood obesity. Other weight loss agents under investigation are conjugated linoleic acid, liraglutide and exenatide (GLP-1 analogues). Bariatric surgery in adolescents is limited to the most critically affected.
In conclusion, there are several unanswered questions pertinent to the definition and the utility of the diagnosis of MetS in children. Since it is an escalating health concern, paediatricians need to focus on primary preventative measures and risk reduction. It is important to screen children with risk factors and employ targeted intensive intervention efforts to those in greatest need.
Dr Lakshmi Prashanth MD
Consultant Pediatrician
Kauvery Hospital Chennai