Recent genetic association studies have identified variants in the Peptidyl-Glycine alpha-amidating mono-oxygenase (PAM) gene that increase the risk of diabetes likely through a defect in beta-cell function. This has been followed up and supported by novel kinetic assays and cellular studies. This investigation will recall heterozygous carriers of the risk allele at rs78408340 and age, BMI and gender matched controls from the Oxford Biobank. The study will compare the incretin effect, glucagon-like peptide-1(GLP-1), insulin, glucose levels and PAM protein activity in individuals both with and without the risk variant. The aim of the study is to gain mechanistic insight into the effect of the variant on human physiology and diabetes pathogenesis.

NCT02723110

Conditions

1. Type 2 Diabetes

Interventions

1. Other: 4 Hour Frequently Sampled Oral Glucose Tolerance Test
2. Other: Isoglycaemic Clamp

MeSH:Diabetes Mellitus Diabetes Mellitus, Type 2 Insulin Resistance Hyperglycemia

HPO:Diabetes mellitus Hyperglycemia Insulin resistance Postprandial hyperglycemia Type II diabetes mellitus

This investigation will recall heterozygous carriers of the risk allele at rs78408340 and age, BMI and gender matched controls from the Oxford Biobank.