Abstract
Aims/hypothesisThere is considerable variability in how diabetes progresses after diagnosis. Progression modelling has largely focused on ‘time to failure’ methods, yet determining a ‘coefficient of failure’ has many advantages. We derived a rate of glycaemic deterioration in type 2 diabetes, using a large real-world cohort, and aimed to investigate the clinical, biochemical, pharmacological and immunological variables associated with fast and slow rates of glycaemic deterioration.MethodsAn observational cohort study was performed using the electronic medical records from participants in the Genetics of Diabetes Audit and Research in Tayside Study (GoDARTS). A model was derived based on an individual’s observed HbA1c measures from the first eligible HbA1c after the diagnosis of diabetes through to the study end (defined as insulin initiation, death, leaving the area or end of follow-up). Each HbA1c measure was time-dependently adjusted for the effects of non-insulin glucose-lowering drugs, changes in BMI and corticosteroid use. GAD antibody (GADA) positivity was defined as GAD titres above the 97.5th centile of the population distribution.ResultsThe mean (95% CI) glycaemic deterioration for type 2 diabetes and GADA-positive individuals was 1.4 (1.3, 1.4) and 2.8 (2.4, 3.3) mmol/mol HbA1c per year, respectively. A younger age of diagnosis, lower HDL-cholesterol concentration, higher BMI and earlier calendar year of diabetes diagnosis were independently associated with higher rates of glycaemic deterioration in individuals with type 2 diabetes. The rate of deterioration in those diagnosed at over 70 years of age was very low, with 66% having a rate of deterioration of less than 1.1 mmol/mol HbA1c per year, and only 1.5% progressing more rapidly than 4.4 mmol/mol HbA1c per year.Conclusions/interpretationWe have developed a novel approach for modelling the progression of diabetes in observational data across multiple drug combinations. This approach highlights how glycaemic deterioration in those diagnosed at over 70 years of age is minimal, supporting a stratified approach to diabetes management.
Highlights
Type 2 diabetes is a progressive disease, primarily characterised by beta cell failure [1, 2]
GAD antibody (GADA)-positive individuals were diagnosed at a younger age and with a lower BMI, lower triacylglycerols and higher HDL-cholesterol, and were more likely to progress to insulin than were individuals with type 2 diabetes
Observational, population-based study with a maximum follow-up period of over 20 years, we have applied a novel approach to modelling the progression of diabetes
Summary
Type 2 diabetes is a progressive disease, primarily characterised by beta cell failure [1, 2]. Previous studies have investigated factors associated with the rate of diabetes progression These studies have only reported an outcome based on progression to glucoselowering medications (i.e. time to initiation of non-insulin glucose-lowering medication, failure of monotherapy or time to insulin therapy) [1, 3,4,5,6,7,8,9]. In these studies, younger age at diagnosis and insufficient beta cell function were consistently associated with faster progression of diabetes. The UK Prospective Diabetes Study (UKPDS) reported that the presence of positive GAD antibody (GADA) concentrations predicted an increased likelihood of requirement for insulin [3]
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