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Characterising the Pre-diabetic Asian and Caucasian Phenotype: the ‘TOFI’ Profile – 3-year Follow-up

Characterising the Pre-diabetic Asian and Caucasian Phenotype: the ‘TOFI’ Profile – 3-year Follow-up: identifying biomarkers of diabetic susceptibility and resilience using a metabolomics platform

Status
Completed
Phases
Unknown
Study type
Observational
Source
ANZCTR
Registry ID
ACTRN12621000001897
Acronym
TOFI_F/U
Enrollment
204
Registered
2021-01-07
Start date
2020-03-02
Completion date
2021-08-06
Last updated
2025-01-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

Background: People of Asian descent are at much higher risk of poor metabolic health and diabetes at a younger age and a lower body weight than those of European Caucasian descent. The reason why some individuals are more susceptible than others and what controls their diabetes risk may lie in the storage of body fat and may be identified through early changes in serum metabolite profile. Gaining even small amounts of body weight can lead to the fat ‘spilling over’ from adipose tissue and into important organs such as the muscle, liver and pancreas, which in turn may significantly increase risk of disease. Often known as the TOFI profile – ‘Thin on the Outside, Fat on the Inside’ – people who appear ostensibly slim and/or mildly overweight can develop diabetes whilst those who are very overweight and/or obese may not. Few predictive biomarkers of early diabetes risk and propensity to susceptibility or resilience have yet been determined. Objective: To investigate diabetic risk profile, susceptibility and resilience to weight gain and increasing adiposity in a population of Asian Chinese and Caucasian adults using body composition and metabolomic techniques; and, to conduct 3-year follow-up to determine whether these markers may predict who worsens towards and/or develops frank diabetes. Design: This is a longitudinal follow-up study of 400 participants, aged 18-70 years, of Asian Chinese (n=200) or Caucasian European (n=200) ethnicity. At baseline and 3-year follow-up, fasting blood samples will be collected to assess diabetic profile based on fasting plasma glucose, and also for untargeted metabolomics profiling; whole body and segmental fat free mass and adipose tissue fat mass will be measured on a single occasion using DEXA scanning; and in a subset of 100 individuals ectopic lipid storage in key organs including liver, pancreas and muscle will be measured using MRI/S.

Interventions

The cross-sectional TOFI Asia study recruited Asian Chinese and European Caucasian adults resident in 2016 in Auckland, New Zealand. Participants were across a wide range of age (18-70 years), body weight, BMI (body-mass index (BMI) between 20-45 kg/m2) and glycaemia; with both normoglycaemic and moderately hyperglycaemic (pre-diabetic) included. Current or prior diagnosis of type 2 diabetes (T2D) was an exclusion criterion. The cohorts were matched for gender, age and BMI. Phenotype characteris

The cross-sectional TOFI Asia study recruited Asian Chinese and European Caucasian adults resident in 2016 in Auckland, New Zealand. Participants were across a wide range of age (18-70 years), body weight, BMI (body-mass index (BMI) between 20-45 kg/m2) and glycaemia; with both normoglycaemic and moderately hyperglycaemic (pre-diabetic) included. Current or prior diagnosis of type 2 diabetes (T2D) was an exclusion criterion. The cohorts were matched for gender, age and BMI. Phenotype characteristics were measured once in the fasted state and these included anthropometry, body composition including whole body, visceral and ectopic organ fat, and clinical blood biomarkers related to T2D risk, in addition to serum metabolomics and faecal microbiome. The anticipated duration of the assessments is approximately 2 hours In order to determine whether these markers may predict who worsens towards and/or develops diabetes, longitudinal follow up will be conducted. The 3-year follow-up study will measure anthropometry and fasted blood samples once in the fasted state. Participants will also have once dual-energy x-ray absorptiometry (DXA) scan to determine total and regional body fat, and collect a stool/faecal sample, for gut microbiome. 100 female participants, due to gender differences in body composition, will additionally undertake a single Magnetic Resonance Imaging and Spectroscopy (MRI/S) scan, to determine ectopic and/or non-adipose tissue organ fat in pancreas and liver. They will also complete a short sub-maximal cardiorespiratory fitness (CRF) test. The MRI/S scan will take about 40 minutes to complete. A subset of these women (n=25) who additionally also had their MRI/S scan will be invited to have a single intravenous glucose tolerance test (ivGTT) as a measure of insulin secretion in the fasted state. The test will take 1 hour and will involve Will also recruit a new cohort of Asian Chinese and Caucasian participants, to the study, who will undergo baseline testing (as done in 2016 for the TOFI_Asia participants) and subsequent 3 year follow-up in 2023-24. All new participants will meet the following criteria: Asian (mainland Chinese; Hong Kong, Taiwan, Singapore or Malaysian Chinese; or Korean) or Caucasian European ethnicity, aged 18-70 years old, normal weight or overweight with a body mass index (BMI=weight/height2) of between 20-50kg/m2, but are otherwise healthy. Participants will be matched for gender, age and BMI. Phenotype characteristics that will be measured will include anthropometry, body composition and clinical blood biomarkers related to T2D risk, in addition to serum metabolomics and faecal microbiome.

Sponsors

University of Auckland
Lead SponsorUniversity

Eligibility

Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No

Inclusion criteria

Participants of both gender, (i) between 18–70 years (ii) BMI 20–45 kg/m2 (iii) both parents of the same ethnic origin, either European Caucasian or Asian Chinese (including mainland China, Singapore, Malaysia, Hong Kong, Taiwan, and Korea) (iv) normo- or dysglycaemic (fasting plasma glucose, FPG: 5·6–6·9 mmol/L)

Exclusion criteria

*Recent body weight loss/gain >10%, within previous 3 months *Recent bariatric surgery, within previous 6 months *Significant current disease *Pregnant or breastfeeding women *Standard exclusions for DXA and MRI scanning techniques, including cardiac pacemaker

Outcome results

None listed

Source: ANZCTR · Data processed: Feb 4, 2026