KKH clinical research coordinator, Ms Foo Chuan Ping, simulates collecting a saliva sample from a study participant.

 

Joining the nationwide effort against diabetes, KKH and NDCS researchers are teaming up to better predict the risk of diabetes and other metabolic complications in obese children and adolescents through salivary amino acid profiling.

Insulin resistance has been shown to predict the development of glucose intolerance (impaired fasting glucose, impaired glucose tolerance and Type 2 diabetes mellitus), and associated complications such as dyslipidaemia and hypertension.

Recent studies have shown that circulating plasma levels of branch chain amino acids (BCAA) and aromatic amino acids have been correlated with measures of insulin resistance and can potentially be surrogate markers to predict the risk of diabetes.

 

PREDICTING INSULIN RESISTANCE

“We hope to study the utility of saliva as an accurate measure of the BCAA profile. By identifying these biomarkers in plasma and saliva, we can potentially predict insulin resistance. We may someday be able to use saliva to determine the likelihood of future diabetes risk in obese children and adolescents," says Primary Investigator Dr Oh Jean Yin, Deputy Head, Department of Paediatrics and Senior Consultant, Adolescent Medicine Service, KKH.

The team aims to collect saliva samples from 115 overweight and severely overweight children and adolescents attending the KKH Paediatric Weight Management Clinic who are between six to 18 years old and exhibit clinical indications requiring blood tests for metabolic screening.

A minute amount of blood will be taken from existing samples collected during patients’ routine fasting blood tests, and both blood and saliva samples will be analysed to measure serum and saliva concentrations of BCAAs.

Data from the study will be used to examine the association between elevations in the fasting concentration of plasma BCAAs, measures of insulin resistance and the severity of childhood obesity.

While insulin resistance often develops in adolescence, the presence of obesity worsens the process, as children and adolescents with a higher body mass index (BMI) have a higher risk of cardiometabolic complications such as dyslipidaemia, hypertension, hyperinsulinaemia and glucose intolerance.

It is estimated that 10 to 25 per cent of obese children have impaired glucose tolerance that may not be clinically apparent for many years.

 

IDENTIFYING CHILDREN AT RISK

Efforts to identify children and adolescents at risk of the development of atherosclerotic cardiovascular disease and Type 2 diabetes mellitus using BMI, waist circumference, systolic blood pressure, serum triglycerides and HDL cholesterol and glucose tolerance have long been debated to have their limitations because of the influence of age, gender and race, stage of puberty.

“We hypothesise that plasma and salivary levels of BCAAs such as leucine, isoleucine and valine may be more reliable biomarkers in predicting the future risk for cardiometabolic disease in obese adolescents, even before early disease is present,” says Dr Oh.

Based on the findings of the first-phase study, a follow-up collaborative study is also planned to examine the subset of patients with elevated BCAA levels but no baseline insulin resistance every six months for up to two years, to monitor for possible future development of insulin resistance.

These findings will have significant clinical relevance, where salivary BCAA as a clinical tool may be an extremely acceptable method for screening children and adolescents at risk of development of
Type 2 diabetes mellitus.

“The development of such alternative, painless methods of screening children and adolescents enhances our ability to identify at-risk groups early, and enables us to implement more targeted and effective weight management and lifestyle interventions for these children,” says Dr Oh.

Members of the KKH-NDCS research team include: Principal Investigator, Dr Oh Jean Yin, Deputy Head, Department of Paediatrics and Senior Consultant, Adolescent Medicine Service, KKH; and co-investigators Dr Ho Meng Fatt, Principal Investigator, Department of Research, NDCS; Dr Kumudhini Rajasegaran, Head and Senior Consultant; Dr Elaine Chew, Consultant; Dr Alison Snodgrass, Consultant, Adolescent Medicine Service; Dr Siew Jia Xuan, Consultant, General Paediatrics Service; and Dr Saumya Jamuar, Consultant, Genetics Service, KKH.

The investigators of this study also gratefully acknowledge the generous support of the Tan Cheng Lim Research and Education Fund.

 

INNOVATING FOR THE FUTURE

To improve the lives and health of future generations, clinician researchers and scientists at KK Women’s and Children’s Hospital (KKH) are pioneering innovative ways to advance women’s and children’s health outcomes. Supported by $7 million in centre grants from the National Medical Research Council, researchers from KKH, in collaboration with National Dental Centre Singapore, SingHealth Polyclinics and National Healthcare Group Polyclinics, are exploring key areas which impact women’s and children’s health and wellbeing, including auto-immunology, childbirth and persistent pain, genetics, metabolic syndromes and endometriosis.

Key research areas: