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

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ClinicalTrials.gov Identifier: NCT04011904
Recruitment Status : Recruiting
First Posted : July 9, 2019
Last Update Posted : July 9, 2019
Sponsor:
Collaborators:
Steno Diabetes Center Copenhagen
Novo Nordisk A/S
Information provided by (Responsible Party):
Professor Lotte Lauritzen, University of Copenhagen

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.


Condition or disease Intervention/treatment Phase
T2D Other: Cross-over study Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Investigator)
Primary Purpose: Prevention
Official Title: The Role of Traditional or Western Diet in the TBC1D4 Gene on Glucose
Actual Study Start Date : April 15, 2019
Estimated Primary Completion Date : July 15, 2019
Estimated Study Completion Date : September 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Traditional Inuit Diet
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
Traditional Inuit Diet vs Westernized Diet

Placebo Comparator: Westernized Diet
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
Traditional Inuit Diet vs Westernized Diet




Primary Outcome Measures :
  1. Changes in 2-h post-OGTT glucose in blood between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    2 hour post oral glucose tolerance test glucose mesurement in blood (mmol/L)


Secondary Outcome Measures :
  1. Changes in Hba1c between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    fasting measurement of blood glycated hemoglobin (%)

  2. Changes in fasting blood glucose between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Fasting measurement of blood glucose (mmol/L)

  3. Changes in 30 min post OGTT between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Measurement of blood glucose 30 min after OGTT (mmol/L)

  4. Continuous glucose monitoring [ Time Frame: Week 2 and Week 6 ]
    Continuous glucose monitor from Abbott is worn for 14 days in each period providing glucose measurements continuously (mmol/L).

  5. Insulin sensitivity and secretion [ Time Frame: Week 1, Week 4 and week 8 ]
    Measured as part of the OGTT. Plasma glucose (mmol/l). Plasma insulin - fasting (pmol/l)

  6. Changes in blood lipids between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Measurements of total and HDL cholesterol (mmol/L) and triglycerides (mmol/L).

  7. Changes in gastrointestinal hormones between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Measurements of e.g. GLP-1, PYY and GIP (pmol/L) in blood.

  8. Changes in gut microbiota composition between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Measured on fecal samples

  9. Changes in C-Reactive Protein between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Blood measurements of C-Reactive Protein (mg/L)

  10. Changes in Interleukin-6 between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Blood measurements of Interleukin-6 (pg/mL)

  11. Changes in small metabolites between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Measured using blood metabolomic measurements of amino acids, lipids, and other small metabolites (umol/L)

  12. Changes in weight between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Measured using a Tanita body composition analyser. Body weight in kilograms

  13. Changes in body composition between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Measured using a Tanita body composition analyser. Fat free mass and Body fat mass in kilograms used to calculate body fat percentage.

  14. Changes in waist and hip circumference between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Measured using measurement tape

  15. Changes in fatty acids (compliance measurement) between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Objective measures of compliance with fish intake, fatty acids (%FA) in blood.

  16. Changes in alkylresorcinols (compliance measurement) between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Objective measures of compliance with grain intake, alkylresorcinols (umol/L) in blood.

  17. Changes in blood pressure (BP) between the baseline and endpoint change in the two periods [ Time Frame: Week 1, Week 4 and week 8 ]
    Systolic BP (mmHG) Diastolic BP (mmHG)



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04011904


Contacts
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Contact: Mads V Lind, PhD 35331091 madslind@nexs.ku.dk
Contact: Lotte Lauritzen, Professor ll@nexs.ku.dk

Locations
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Denmark
Department of Exercise, Nutrition and Sports, Faculty of Sciences, University of Copenhagen Recruiting
Copenhagen, Denmark
Contact: Mads V Lind    +4535331091      
Sponsors and Collaborators
University of Copenhagen
Steno Diabetes Center Copenhagen
Novo Nordisk A/S

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Responsible Party: Professor Lotte Lauritzen, Professor, University of Copenhagen
ClinicalTrials.gov Identifier: NCT04011904     History of Changes
Other Study ID Numbers: KVUG 2018-26
First Posted: July 9, 2019    Key Record Dates
Last Update Posted: July 9, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Professor Lotte Lauritzen, University of Copenhagen:
Greenland Inuit
Traditional diet
TBC1D4