Title: Deriving evidence-based clinical criteria to aid classification of diabetes
Funder: Department of Health (England)

Abstract: There are two main subtypes of diabetes: Type 1 diabetes (~15%) and Type 2 diabetes (~83%)[1], in addition to rare monogenic or secondary forms of diabetes. The type of diabetes a patient has is determined by their clinician at diagnosis. Clinical management of the two types is very different in terms of the treatment for the diabetes, the education provided, and monitoring required, so a correct classification is vital for appropriate patient care. These differences are due to the presence (Type 2) or absence (Type 1) of endogenous insulin secretion. However, measures of insulin secretion are seldom carried out in practice, and there are no clear clinical criteria to aid classification decisions. Recent studies in general practice suggest 13-16% of patients with diabetes are misclassified, so there is a clear need for evidence-based clinical guidelines to aid classification. We aim to derive a set of clinical diagnostic criteria that reflect a patient’s underlying endogenous insulin secretion, which could be used to aid classification of diabetes. To achieve this, we propose three stages of work: 1) A systematic review will be undertaken to identify, critique and synthesise the evidence on clinical criteria to predict absolute insulin deficiency, that could be used to classify Type 1 diabetes (with Type 2 diabetes being defined on the basis of exclusion of Type 1). A set of criteria will be derived based on the synthesis of the results from the scientific literature. Age at diagnosis of diabetes and BMI are likely to be identified as the most discriminatory characteristics, but we will investigate all those in the literature that are relevant. We will evaluate the diagnostic performance of characteristics using hierarchical summary receiver operating characteristic (ROC) curve analysis, as proposed by the Cochrane guidelines for systematic reviews of diagnostic test accuracy. We will also incorporate any other clinical features identified as useful either using linked ROC curves or on a rational basis. 2) We will then test the criteria established in part (1) in 1600 patients recruited through primary care, on which we have measures of clinical characteristics and insulin deficiency. This will provide evidence of sensitivity and specificity of the criteria for correctly identifying insulin deficiency in a community-based cohort. This will form a validation step to determine the discriminative ability of the criteria for correctly classifying diabetes. We will also test whether there is a small subgroup of patients in which criteria are not helpful, in which it would be useful to advise direct measurement of insulin deficiency. Finally, we will assess the improvement in diagnostic accuracy using the new criteria compared with current practice. 3) We will disseminate the validated criteria through regional, national and international meetings, and submit the evidence to Diabetes UK, NICE and WHO for incorporation into their patient and professional guidance and guidelines for classification of diabetes.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: METABOLIC AND ENDOCRINE