The Role of Traditional or Western Diet in the TBC1D4 Gene on Glucose Homeostasis in Greenland Inuits

NCT04011904 | Completed DMC

• 1 other identifier: KVUG 2018-26
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Studies of Greenland Inuit before the 1980s found a low prevalence of type 2 diabetes (T2D) compared to Western populations. However, recent population studies in Greenland found a notably high prevalence of diabetes (9%) and pre-diabetes (19%) in the adult population. In many studies worldwide an increase in obesity, diabetes, and cardiovascular disease has been ascribed to social transition and in particular urbanization, but the Inuit in Greenland do not fit the pattern. Paradoxically, the highest prevalence of diabetes is seen in the least urbanized areas. Thus, while previously rare, T2D has become epidemic in Inuit. In a recent study by Moltke et al found that a variant in the TBC1D4 gene was strongly associated with insulin resistance in skeletal muscle, high postprandial blood glucose and a high risk of T2D. The rapid increase in the prevalence of T2D and other metabolic traits and the well documented genetic susceptibility indicates that lifestyle components, particularly physical activity, and diet significantly modify the genetic effects on glucose homeostasis. Thus, changing dietary habits from a diet high in traditional foods, mostly consisting of marine mammals and fish (high in protein and unsaturated fats, and low in carbohydrate) to a westernized diet, with high contents of sugar and saturated fat may have increased the T2D incidence in Arctic Inuit. The investigators will perform a 4-week cross-over intervention study of the traditional diet versus a western diet among homozygous carriers and WTs on 2-hour glucose after an oral glucose tolerance test (OGTT). In addition, the investigators will examine the effects on cardiometabolic abnormalities such as low-grade systemic inflammation and dyslipidemia. Furthermore, the investigators will characterize the metabolic phenotype of participants, as well as gut microbiota and brown adipose tissue markers to elucidate the molecular mechanisms underlying potential improvements of a traditional Inuit diet.

Conditions

T2D

Keywords

Greenland Inuit; Traditional diet; TBC1D4

Outcome Measures

Primary Outcomes (1)

• Changes in 2-h post-OGTT glucose in blood between the baseline and endpoint change in the two periods

  2 hour post oral glucose tolerance test glucose mesurement in blood (mmol/L)

  Week 1, Week 4 and week 8

Secondary Outcomes (17)

• Changes in Hba1c between the baseline and endpoint change in the two periods

  Week 1, Week 4 and week 8

• Changes in fasting blood glucose between the baseline and endpoint change in the two periods

  Week 1, Week 4 and week 8

• Changes in 30 min post OGTT between the baseline and endpoint change in the two periods

  Week 1, Week 4 and week 8

• Continuous glucose monitoring

  Week 2 and Week 6

• Insulin sensitivity and secretion

  Week 1, Week 4 and week 8

Study Arms (2)

Traditional Inuit Diet

EXPERIMENTAL

This will be a traditional Inuit diet (TID) rich in marine mammals (such as walrus, seal, and whale), fish, caribou and musk ox, with low intake of grains, fast food and other imported foods. The TID diet will be high in fat (\>40 of the energy (E%)) and low in carbohydrate (\<30 E%).

Other: Cross-over study

Westernized Diet

PLACEBO COMPARATOR

This will be a Westernized diet will be consisting of high amounts of grains, potatoes, rice and imported meats from livestock animals (beef, pork and chicken). The Westernized diet will be high in carbohydrate (55-65 E%) and lower in fat (30-35 E%).

Other: Cross-over study

Interventions

Cross-over study OTHER

Traditional Inuit Diet vs Westernized Diet

Traditional Inuit Diet; Westernized Diet

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who have provided written informed consent
• Age between 18 and 80 years
• Homozygous carriers of the nonsense p.Arg684Ter variant in the TBC1D4 gene (cases)
• Homozygous non-carriers of the nonsense p.Arg684Ter variant in the TBC1D4 gene (control)

You may not qualify if:

• If study participants do not want to know whether they are carriers or non-carriers of the p.Arg684Ter variant in the TBC1D4 gene they will not be able to participate in the study
• BMI ≥ 18.5 kg/m2
• Diagnosis of diabetes (HbA1c ≥ 6,5% (48 mmol/mol)) or pharmacological treatment of diabetes (10).
• Use of peroral glucocorticoids
• Lack of compliance with the procedures in the study protocol, judged by Investigator

Sponsors & Collaborators

• University of Copenhagen: lead
• Steno Diabetes Center Copenhagen: collaborator
• Novo Nordisk A/S: collaborator

Study Sites (1)

Department of Exercise, Nutrition and Sports, Faculty of Sciences, University of Copenhagen

Copenhagen, Denmark

Location

Related Publications (1)

• Moller G, Lind MV, Hauptmann AL, Senftleber N, Hansen CB, Hansen T, Jorgensen ME, Lauritzen L. The role of a traditional and western diet on glucose homeostasis in Greenlandic Inuit carriers and non-carriers of type 2 diabetes variant in the TBC1D4 gene: A protocol for a randomized clinical trial. Contemp Clin Trials Commun. 2021 Jan 27;21:100734. doi: 10.1016/j.conctc.2021.100734. eCollection 2021 Mar.

  PMID: 33604488 DERIVED

MeSH Terms

Interventions

Cross-Over Studies

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 13, 2019
• First Posted: July 9, 2019
• Study Start: April 15, 2019
• Primary Completion: November 23, 2020
• Study Completion: November 23, 2020
• Last Updated: November 25, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)