Prediabetes is a state of glycaemic dysregulation below the diagnostic threshold of type 2 diabetes (T2D). Globally, ~352 million people have prediabetes, of which 35–50% develop full-blown diabetes within five years. T2D and its complications are costly to treat, causing considerable morbidity and early mortality. Whether prediabetes is causally related to diabetes complications is unclear. Here we report a causal inference analysis investigating the effects of prediabetes in coronary artery disease, stroke and chronic kidney disease, complemented by a systematic review of relevant observational studies. Although the observational studies suggest that prediabetes is broadly associated with diabetes complications, the causal inference analysis revealed that prediabetes is only causally related with coronary artery disease, with no evidence of causal effects on other diabetes complications. In conclusion, prediabetes likely causes coronary artery disease and its prevention is likely to be most effective if initiated prior to the onset of diabetes.

Introduction/Aims: Electrodiagnostic testing (EDX) is important in evaluation of pediatric neuromuscular disease. Non-specific referrals have emerged as a leading reason for EDX in recent years. We examine whether referral-specificity is predictive of test outcomes in children.Methods: EDX referrals and outcomes were audited over a 7-year period from 2013 to 2020 at CHI-Crumlin. Pre-test details were coded and compared to EDX outcomes using multinomial logistic regression.Results: EDX studies were performed in 702 children (median age 10.2 years). In 36% of patients, EDX-referrals did not specify any pre-test diagnosis. Mononeuropathy (24%) and polyneuropathy (15%) were the leading pre-specified diagnoses as well as the most common test outcomes. Neurology and orthopedics/plastic surgery contributed the majority of referrals. Metabolic medicine and hematology/oncology were most likely to pre-specify a working diagnosis and were the specialties with both the highest proportion of abnormal outcomes and referral accuracy. EDX abnormality was present in 42% of patients and was predicted by specificity of referral and the absence of pain as a leading symptom. The accuracy of specified pre-test diagnoses was highest for suspected anterior horn cell disorders (67%). Accuracy of referrals, as well as abnormal test outcomes, were negatively predicted by the presence of pain as a leading symptom.Discussion: EDX is informative in children but the likelihood of abnormal testoutcomes is diminished when a pre-specified working diagnosis is lacking or when the primary reason for referral is pain.

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A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20663-6

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