Gastric Emptying - Implications for the Pathogenesis of Type 2 Diabetes
Gastric Emptying - Implications for the Pathogenesis of Type 2 Diabetes
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.
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
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)