Author: Linxi Mytkolli

The cause of type-1 diabetes is still unknown with many factors at play but none conclusive. Scientists have however learned that type 1 diabetes begins years before it is diagnosed when a person’s own immune system launches subtle attacks on the beta cells in the pancreas. In a recent study, Herold et al. 2019, discovered that the an anti-CD3 antibody, Teplizumab, originally intended to protect new organs after kidney transplantation, could deactivate T cells that are targeting insulin producing beta cells.   This study investigated people who were at high risk of developing type-1 diabetes (have a first degree relative with type-1) but had not yet been diagnosed.  Using a double-blind randomized method, participants were assigned a single 14-day course of Teplizumab or placebo and follow-up tests for progression to type-1 diabetes were performed at 6-month intervals.  The results showed that a single dose of Teplizumab delayed progression of type-1 diabetes by approximately two years in those at risk of developing type-1 diabetes.   This is a ground-breaking study as previously there was no tangible method of preventing, or in this case delaying, type-1 diabetes for high risk individuals.   Further investigation of Teplizumab will raise an interesting ethical debate as the findings from this study have proven delayed onset of Type-1 diabetes, and therefore trial design using placebo might be denying participants, particularly children age 12 and below, the opportunity for a delay in a type-1 diabetes clinical diagnosis.

The full research article published in the New England Journal of Medicine can be found here

Part A

Determining what kind of diabetes someone has is not always easy in the adult population. It is becoming clear that T1D is not simply a pediatric disease or a disease of early adulthood – a genetic, population-based UK study suggests that genetically-defined type 1 diabetes between 30 and 60 years of life is a distinct condition with a different clinical course than type 2 diabetes, with lower BMI and more rapid progression to insulin dependence [1]. When defined this way T1D diagnosed after age 30 represents approximately 40% of all cases of T1D but only 4% of all cases of diabetes diagnosed after age 30.  The diagnosis of T1D in people over 30 is obscured by the massive increase in the prevalence of T2D after the age of 30, explaining why it is so easy to misdiagnose T1D in which the onset of diabetes occurs after age 30.

Because genetic testing is not currently performed in patients we typically see in our clinical practice, can we utilize simple and readily available biomarkers such as plasma C-peptide to diagnose T1D in adults, defined by severe endogenous insulin deficiency after age 30 progressing to rapid insulin requirement within 3 years of diagnosis?  A recently published study suggests that transition to insulin requirement within 3 years of diagnosis and very low C-peptide levels (< 200pmol/l or 0.2 nmol/l) identifies individuals who have similar clinical and biological characteristics (such as high islet autoantibody prevalence) to that occurring at younger ages, but is frequently not identified as having T1D[2].  The importance of identifying these patients who demonstrate rapid progression to pancreatic beta cell failure is that they are profoundly insulin deficient and therefore insulin dependent and consequently ketosis prone and are best labelled as having T1D.

Part B

The University of Exeter group has developed an app which can help predict the likelihood of T1, T2 or MODY.

iOS Diabetes Diagnostics* on the App Store – iTunes – Apple

Android Diabetes Diagnostics* – Apps on Google Play

*The Diabetes Diagnostics app is a clinical aid for the differential diagnosis of diabetes subtypes. The app combines information from national and international diabetes guidelines, the MODY clinical prediction calculator, and expert opinion from world leaders in monogenic diabetes to provide a resource to help guide diabetes classification.

[1] Thomas NJ, Jones SE, Weedon MN, Shields BM, Oram RA, Hattersley AT. Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank. The Lancet Diabetes & Endocrinology. 2017 Nov 30;6(2):122–9

[2] Thomas NJ, Lynam AL, Hill AV, Weedon MN, Shields BM, Oram RA, McDonald TJ, Hattersley AT, Jones AG. Type 1 diabetes defined by severe insulin deficiency occurs after 30 years of age and is commonly treated as type 2 diabetes.  Diabetologia. 2019 Apr 10: 1-6