The Role of Traditional or Western Diet in the TBC1D4 Gene on Glucose
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Changes in 2-h post-OGTT glucose in blood between the baseline and endpoint change in the two periods
研究概览
简要总结
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.
详细描述
The overall objective of the study is to investigate whether a traditional marine diet high in fat and low in carbohydrate compared to a westernized diet could improve glycemic control in Greenland Inuit. Furthermore, the objective is to study whether the genetic risk of postprandial hyperglycemia among Greenlandic carriers of the common nonsense p.Arg684Ter variant in the TBC1D4 gene is modified to a larger degree by the diet compared to non-carriers.
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.
The study is expected to provide relevant information in relation to whether diet has a role in preventing T2D in the large group of people who are hetero / homozygous for the TBC1D4 variant. The investigators expect this enhanced insight to be useful and valuable for future development of genotype based interventions for these persons.
For the individual participant, the results of the study are expected to provide constructive knowledge to guide the participants in which actions they could take to reduce the likelihood of developing T2D.
Hypothesis
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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)
排除标准
- •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
结局指标
主要结局
Changes in 2-h post-OGTT glucose in blood between the baseline and endpoint change in the two periods
时间窗: Week 1, Week 4 and week 8
2 hour post oral glucose tolerance test glucose mesurement in blood (mmol/L)
次要结局
- Continuous glucose monitoring(Week 2 and Week 6)
- Changes in blood lipids between the baseline and endpoint change in the two periods(Week 1, Week 4 and week 8)
- Changes in gut microbiota composition between the baseline and endpoint change in the two periods(Week 1, Week 4 and week 8)
- Changes in body composition between the baseline and endpoint change in the two periods(Week 1, Week 4 and week 8)
- Insulin sensitivity and secretion(Week 1, Week 4 and week 8)
- 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)
- Changes in gastrointestinal hormones between the baseline and endpoint change in the two periods(Week 1, Week 4 and week 8)
- Changes in C-Reactive Protein between the baseline and endpoint change in the two periods(Week 1, Week 4 and week 8)
- Changes in Interleukin-6 between the baseline and endpoint change in the two periods(Week 1, Week 4 and week 8)
- Changes in small metabolites between the baseline and endpoint change in the two periods(Week 1, Week 4 and week 8)
- Changes in weight between the baseline and endpoint change in the two periods(Week 1, Week 4 and week 8)
- Changes in fatty acids (compliance measurement) between the baseline and endpoint change in the two periods(Week 1, Week 4 and week 8)
- Changes in alkylresorcinols (compliance measurement) between the baseline and endpoint change in the two periods(Week 1, Week 4 and week 8)
- Changes in blood pressure (BP) between the baseline and endpoint change in the two periods(Week 1, Week 4 and week 8)
- Changes in waist and hip circumference between the baseline and endpoint change in the two periods(Week 1, Week 4 and week 8)
研究者
Professor Lotte Lauritzen
Professor
University of Copenhagen