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BACKGROUND: South Asian adults have higher prevalence of obesity comorbidities than other ethnic groups. Whether this also is true for Sri Lankan children with obesity has rarely been investigated.

OBJECTIVE: To investigate prevalence of glucose intolerance and other comorbidities in Sri Lankan children with obesity and compare them with Swedish children. To identify risk factors associated with glucose intolerance.

SUBJECTS: A total of 357 Sri Lankan children (185 boys), aged 7 to 17 years with BMI-SDS ≥2.0 from a cross-sectional school screening in Negombo. A total of 167 subjects from this study population were matched for sex, BMI-SDS and age with 167 Swedish subjects from the ULSCO cohort for comparison.

METHODS: After a 12 hour overnight fast, blood samples were collected and oral glucose tolerance test was performed. Body fat mass was assessed by bioelectrical impedance assay. Data regarding medical history and socioeconomic status were obtained from questionnaires.

RESULTS: Based on levels of fasting glucose (FG) and 2 hours-glucose (2 hours-G), Sri Lankan subjects were divided into five groups: normal glucose tolerance (77.5%, n = 276), isolated impaired fasting glucose according to ADA criteria (9.0%, n = 32), isolated impaired glucose tolerance (8.4%, n = 30), combined impaired fasting glucose (IFG) + impaired glucose tolerance (IGT) (3.1%, n = 11) and type 2 diabetes mellitus (2.0%, n = 7). FG, 2 hours-insulin and educational status of the father independently increased the Odds ratio to have elevated 2 hours-G. Sri Lankan subjects had higher percentage of body fat, but less abdominal fat than Swedish subjects.

CONCLUSION: High prevalence in Sri Lankan children with obesity shows that screening for glucose intolerance is important even if asymptomatic.

Aim: To investigate the prevalence and possible risk factors for the development of impaired glucose metabolism in children and adolescents with obesity.

Methods: This was a cross-sectional retrospective cohort study, including 634 patients with obesity and 98 normal weight controls aged 4-18 years from the Beta-cell function in Juvenile Diabetes and Obesity (Beta-JUDO) cohort, a dual-centre study at Uppsala University Hospital (Sweden) and Paracelsus Medical University Hospital (Salzburg, Austria) conducted between 2012 and 2021. A longitudinal subgroup analysis, including 188 of these subjects was performed. Impaired glucose metabolism was diagnosed by oral glucose tolerance tests according to American Diabetes Association criteria.

Results: The prevalence of impaired glucose metabolism was 72% in Uppsala patients, 24% in Salzburg patients, 30% in Uppsala controls and 13% in Salzburg controls. The prevalence was lower at the follow-up visits compared with baseline both in Uppsala and Salzburg patients. A family history of type 2 diabetes showed the strongest association with impaired glucose metabolism at the follow-up visits besides belonging to the Uppsala cohort.

Conclusion: The prevalence of impaired glucose metabolism was extraordinarily high in Swedish children and adolescents with obesity, but decreased during the follow-up period.

Background

Associations between mast cell activity, obesity and glucose metabolism have been found in adults and animal models, but not investigated in pediatric obesity.

Aims

To compare biomarkers associated with mast cell activity in children with obesity to normal weight controls and to investigate associations between these biomarkers and glucose metabolism in pediatric obesity.

Methods

Children with obesity (n=154, age 4-18 years) and normal weight controls (n=30, age 6-17 years) from the Uppsala Longitudinal Study of Childhood Obesity (ULSCO) cohort were included and underwent an oral glucose tolerance test (OGTT). Proinsulin and HbA1c were measured fasting. Mast cell activity was assessed by measurement of tryptase, diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT) and adjusted for specific immunoglobulin E (IgE) and C-reactive protein (CRP). 

Results

Among the markers associated with mast cell activity, HNMT levels were significantly higher in patients with obesity than in controls (median value 8.4 vs 7.7 NPX, p<0.001). In multiple linear regression analyses adjusted for age, sex, BMI-SDS, specific IgE and CRP, HNMT showed an independent association with fasting proinsulin (β=0.120, p=0.003).

Conclusions

These findings indicate that associations between mast cell activity, obesity and beta-cell stress are present already in children and adolescents.

Background

Pharmacological treatment options for children and adolescents with obesity are limited. Clinical trials with metformin in pediatric obesity have shown mixed results depending on dosage and age. In adults, metformin extended release (XR) has shown promising results on Body Mass Index (BMI) with fewer side effects.

Objectives

The primary objective was to investigate the effect of metformin XR together with lifestyle intervention compared with lifestyle intervention alone on BMI-standard deviation score (SDS). Secondary objectives included the effect on BMI-SDS of metformin immediate release (IR) together with lifestyle intervention compared with lifestyle intervention alone, as well as effects on glucose metabolism and cardiometabolic risk factors in the different groups. Furthermore, to determine the effect of plasma metformin concentration and age on the treatment effect, as well as the safety and tolerability of metformin in children and adolescents with obesity.

Methods

A parallel, three-armed, randomized, 6 months multi-center study with an extended-release metformin formulation (Glucophage® SR) combined with lifestyle intervention (XR+L), an immediate-release metformin formulation (Glucophage®) combined with lifestyle intervention (IR+L), or lifestyle intervention alone (LA). Children and adolescents aged 6-17 years with obesity (BMI-SDS >2.0) were included. Dosage of metformin was based on body weight. Metformin concentration was measured in plasma and urine. Lifestyle modification interventions were given to all participants at all study contacts during the treatment period. Oral glucose tolerance tests (OGTT) were conducted at the beginning and end of the intervention.

 Results

 Participants (89, of which 45 females, mean age 11.9 years, range 7-17 years, mean BMI-SDS 3.1) were randomized, and 77 participants completed the study. The treatment effect of XR+L compared with LA was -0.132 BMI-SDS (p=0.02). Mean BMI-SDS change from baseline to the end of the study was for the XR+L group -0,281 (p= 0.006), for the IR+L group -0,280 (p= 0,009), and for the LA group -0,126 (p= 0.359). A significant reduction in S-Insulin and P-Glucose was seen at several timepoints during OGTT in the IR+L group. Metformin concentration had no effect on the change in BMI-SDS. The treatment effect of XR+L or IR+L compared with LA was more pronounced in older children. Safety and tolerability profiles were comparable in all three groups.

 Conclusions

 Treatment with metformin XR + lifestyle led to a clinically significant BMI-SDS reduction in children and adolescents with obesity compared to lifestyle alone. Both extended and immediate release metformin formulations, are effective in lowering BMI-SDS, safe and generally well tolerated from the age of 7 years. Metformin is therefore suitable for treating pediatric obesity.