Gastric Emptying - Implications for the Pathogenesis of Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Observational

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
    

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
      
Keywords: gastric emptying; oral glucose tolerance test; Ethnicity; Diabetes risk