DIabetes ResearCh on patient straTification. (WC2011-078)

Methods

Starting date: 01/01/2012

We will undertake very detailed phenotyping in 3,000 people at high risk of developing type 2 diabetes. We will follow this cohort and undertake assessments of HbA1c every 3 months until an 18-month follow-up visit. At this point, we will repeat the detailed metabolic phenotyping performed at baseline in those in whom glycemic control is deteriorating slowly (n=300) or rapidly (n=300) as determined by the change in HbA1c over time. This sub-cohort will be followed for a further 18 months, HbA1c will continue to be sequentially assessed, and a full re-examination will be performed. There are several attractive features of this experimental design; the first is that because participants will be selected as those at high risk of diabetes based on conventional risk markers, we will control for these risk factors, thus reducing variability in glycaemic deterioration attributable to these factors. The second major strength of this design is that a wealth of existing data relevant to the aims of the DIRECT project has already been collected in these participants as part of other cohort studies. These data will be available to the DIRECT consortium and will be used to identify biomarkers for glycaemic deteriorating. The third major strength of this study design is that we will obtain repeated measures of glycemia (HbA1c) in each participant. The availability of these data will allow use to study the dynamic relationship between biomarkers and glycaemic deterioration. This is of particular interest, as the rate of glycaemic control tends to accelerate in the years immediately preceding diabetes onset. Given the high-risk nature of this cohort and the availability of repeated measures of glycaemia, it is possible that we may observe people as they progress through this point, and potentially identify biomarkers for this trait.