Clinical trial NCT03864562: Gastric Emptying - Implications for the Pathogenesis of Type 2 Diabetes
Official title: Gastric Emptying in Non-diabetic Individuals With Black African/Caribbean Heritage - Implications for the Pathogenesis of Type 2 Diabetes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Mellitus, Type 2
Keywords: gastric emptying
oral glucose tolerance test
Ethnicity
Diabetes risk
Lead sponsor: University of Nottingham
Sponsor class: OTHER
Collaborators: name: University of Adelaide
First posted: 2019-03-06
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study cohort will be recruited from the general population of England who live within commuting distance from the study site, and will incorporate those from the counties of Nottinghamshire, Derbyshire and Leicestershire

Brief summary: People of black African and Caribbean descent have a greater risk of developing type 2 diabetes than white Europeans. The aim of this study is to increase our knowledge of how the condition may arise, and what underlies this increased risk. Following a successful screening visit to confirm eligibility for the study, we will be investigating how quickly a glucose drink empties out of the stomach in 30 white Europeans and 30 people of black African or Caribbean descent. In addition, we will study the impact that gastric emptying rate has on blood glucose and satiety hormones released normally by the gut in response to eating. Blood and breath samples will be collected before and during an oral glucose tolerance test.

Detailed description: Background It is recognized that there are differences between ethnic groups in the risk of developing type 2 diabetes (T2D), but the underlying pathophysiology remains poorly defined. For example, whilst insulin resistance, exacerbated by obesity, is common in Caucasian, Hispanic and South Asian populations, impairment in insulin secretion appears to be the primary defect in the pathogenesis of T2D in East Asians. Within the United Kingdom (UK), diabetes and its complications disproportionately affect ethnic minority groups, particularly those of black African-Caribbean (AfC) descent. Studies indicate that the rate of gastric emptying is a major determinant of postprandial glycemia and insulinemia in those with a White European (WE) background in both health and T2D, and although there is evidence that gastric emptying is influenced by ethnicity (which may contribute to the development of T2D), gastric emptying has, to our knowledge, not been evaluated in those of AfC heritage.

Aims The primary objective is to compare the gastric emptying rate in 2 UK ethnic groups. This will be done by conducting a descriptive, cross-sectional pilot study in 60 healthy participants. Secondary objectives are to determine any relationship between glycemia, insulinemia and incretin hormone secretion in these groups.

Experimental protocol Sixty volunteers; 30 of WE and 30 of black AfC heritage will be recruited. Following a successful medical screening visit, participants will be asked to record their dietary intake over 3 days before attending the laboratory for their study visit. On the day before the study visit they will be asked to avoid strenuous exercise, alcohol and caffeine intake and to eat their normal diet. On the study day, participants will arrive at the laboratory in the morning following an overnight fast. A cannula will be inserted into a vein in the top of the hand and the hand placed in a warming box for repeat arterialized-venous blood sampling over the study day. After baseline breath and blood samples have been taken, participants will then be given a drink containing 75g of glucose dissolved in 300ml water (standard oral glucose tolerance test), to which has been added 150mg of 13C labelled acetate, and asked to consume it within 5 minutes. The stable isotope label on the acetate allows us to assess gastric emptying by detecting the appearance of 13CO2 in breath. Blood samples (6ml) will be collected prior to the drink, with further samples being taken every 15min for the first 2hrs, then every 30min for the next hour, with a final sample taken at 4hrs. Blood will be analysed for glucose, insulin, C-peptide, Glucagon-like peptide 1 (GLP-1), glucagon, and Gastric inhibitory polypeptide (GIP). Following the drink, subjects will also be asked to complete satiety and GI symptom questionnaires every half hour throughout the study. At the end of the 4 hours, participants will be asked to complete a series of autonomic function tests, during which we will measure blood pressure and heart rate. These tests are 2mins of rhythmic breathing (5sec inhale: 5sec exhale) and postural change to standing from resting semi-supine. After this time, the cannula will be removed and the study is completed

Eligibility criteria: Inclusion Criteria:

* White European or black African / Caribbean heritage
* BMI \>18 kg/m2
* Ability to give written informed consent
* English speaking

Exclusion Criteria:

* Any significant medical condition
* Uncontrolled hypertension
* Alcohol consumption \>14 units / week
* Random blood Glucose concentration above 7.8mmol/l
* Hemoglobin A1c (HbA1c) \>47mmol/mol (\>6.4%)
* Use of regular medication, (oral contraceptive pill or antihypertensive medication are acceptable if use has been for \>6 months)
* History of Irritable Bowel Syndrome, food intolerances or any gastrointestinal disorders
* Previous bariatric surgery, or gastrointestinal surgery which may affect normal function (e.g. bowel resection)

Primary outcomes:
measure: Gastric emptying rate
timeFrame: 4 hours
Secondary outcomes:
measure: Serum Insulin concentration
timeFrame: 4 hours
measure: Whole blood glucose concentration
timeFrame: 4 hours
measure: Plasma glucagon concentration
timeFrame: 4 hours
measure: Plasma GLP-1 concentration
timeFrame: 4 hours
measure: Plasma GIP concentration
timeFrame: 4 hours
measure: Serum C-peptide concentration
timeFrame: 4 hours
measure: Attrition rate
timeFrame: 1 year
measure: Recruitment rate
timeFrame: 1 year
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: David Greenfield Human Physiology Unit, University of Nottingham
state: Notts
Study officials:
affiliation: University of Adelaide
name: Michael Horowitz, MD PhD
role: STUDY_DIRECTOR
References:
citation: Kodama K, Tojjar D, Yamada S, Toda K, Patel CJ, Butte AJ. Ethnic differences in the relationship between insulin sensitivity and insulin response: a systematic review and meta-analysis. Diabetes Care. 2013 Jun;36(6):1789-96. doi: 10.2337/dc12-1235.
citation: Horowitz M, Edelbroek MA, Wishart JM, Straathof JW. Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects. Diabetologia. 1993 Sep;36(9):857-62. doi: 10.1007/BF00400362.
citation: Phillips WT. Gastric emptying in ethnic populations: possible relationship to development of diabetes and metabolic syndrome. Ethn Dis. 2006 Summer;16(3):682-92.