Aims and Purpose

What was the purpose of establishing the SDRNT1BIO?
What are the overall research aims of the study and how can we utilize this cohort?

Purpose

There are many things doctors and researchers still don’t understand about Type 1 diabetes. For example, we do not fully understand why some people get Type 1 diabetes or how to prevent it. We also do not fully understand why some people seem prone to getting complications of diabetes and others do not. If we could do better at predicting who would get complications, we might be able to intervene earlier and more intensively in those most at risk. Furthermore, some people with a single gene underlying their diabetes (Monogenic Diabetes) continue to be diagnosed as having Type 1 diabetes- we need to improve how we detect monogenic diabetes. 

The availability of large prospective cohorts of patients is pivotal to answer such research questions. The people of Scotland with Type 1 diabetes can make a unique contribution to this research because Scotland has one of the best registers in the world of who has diabetes. This register shows that there are approximately 30,000 people with Type 1 diabetes in Scotland. 

Accordingly, we established the SDRNT1BIO as a large set of samples and data from people with Type 1 diabetes in Scotland- we call this collection of samples and data a “bioresource”. More than 85% of those invited to participate did so, which demonstrates how important people with Type 1 diabetes in Scotland view driving forward research into their condition. We are using the SDRNT1BIO to facilitate a wide range of research into the causes of Type 1 diabetes, diabetes complications and monogenic diabetes. We measure genetic and other "biomarkers" such as proteins and metabolites in the samples taken, before combining this with information on the course of diabetes from the clinical record to discover new knowledge.

Aims

T1DM is partly genetically determined and initial research yielded insights into the potential pathways causing diabetes; some of which are now being targeted by novel intervention therapies. However, several known genetic loci for T1DM do not explain all the known heritability. Among several potential explanations for this “missing heritability” are the existence of rare variants with large effects and the existence of additional more common variants with effects too low to have been detected by sample sizes used so far. Additional discovery work to detect new T1DM loci is warranted, especially for those with older age of onset.


Many complications of diabetes are heritable, justifying attempts to discover their genetic determinants. Few unequivocal replicable genetic associations were previously found, so large scale initiatives are underway although many had previously focused on T2DM than T1DM because of the greater prevalence and availability of larger T2DM cohorts. The data from the SDRNT1BIO will augment existing international efforts to understand the genetics of macro- and micro-vascular complications of diabetes and will yield novel insight into neglected traits, which could be targeted by newly designed treatments.


Several extremely productive prospective cohort studies of T1DM have yielded much of what we know about the pathogenesis and risk factors for complications and how these differ between T1DM and T2DM. To fully exploit modern ‘omic methods for pathway and biomarker discovery, including lipidomics, metabolomics and genomics, and to develop more precise prediction algorithms for complications that incorporate new biomarkers, further large cohorts of T1DM patients, such as SDRNT1BIO, are needed to supplement existing cohorts.


The environmental determinants of T1DM remain largely unknown (although a number of putative factors have been postulated). The SDRNT1BIO can yield useful information on the role of environment, for example by examining how the pattern of potential risk factors varies with genotype or auto-antibody phenotype. For T1DM complications the SDRNT1BIO and linked e-health record data can be used to explore socio-economic differentials and the impact of health care activities on complications.


The gold standard biomarker of endogenous insulin production is C-peptide concentrations. Previously it was believed that those with T1DM have no residual insulin secretion. With the development of ultra-sensitive C-peptide assays, studies have shown that detectable levels of C-peptide are much more common in T1DM than previously thought. Exploring the genetic and immunological differences between those with and without detectable C-peptide might yield possible mechanisms for preserving beta cell function and preventing or even reversing T1DM.

Another aspect of diabetes stratification is the improved detection of maturity onset diabetes of the young (MODY) among those misdiagnosed as having T1DM. Diagnosis of MODY remains difficult and at present it is estimated only around 25% of all MODY are correctly diagnosed. The SDRNT1BIO data will allow us to compare the yield of cases from various detection algorithms.


This article was published on