Abstract
BACKGROUND: Undiagnosed comorbid diseases that independently lead to weight loss before type 2 diabetes mellitus (T2DM) diagnosis could explain the observed increased mortality risk in T2DM patients with normal weight. OBJECTIVES: To evaluate the impact of weight change patterns before the diagnosis of T2DM on the association between body mass index (BMI) at diagnosis and mortality risk. METHODS: This was a longitudinal cohort study using 145,058 patients from UK primary care, with newly diagnosed T2DM from January 2000. Patients aged 18-70, without established disease history at diagnosis (defined as the presence of cardiovascular diseases, cancer, and renal diseases on or before diagnosis) were followed up to 2014. Longitudinal 6-monthly measures of bodyweight three years before (used to define groups of patients who lost bodyweight or not before diagnosis) and 2 years after diagnosis were obtained. The main outcome was all-cause mortality. RESULTS: At diagnosis, mean (SD) age was 52 (12) years, 56% were male, 52% were current or ex-smokers, mean BMI was 33 kg/m(2), and 66% were obese. Normal weight and overweight patients experienced a small but significant reduction in body weight 6 months before diagnosis. Among all categories of obese patients, consistently increasing body weight was observed within the same time window. Among patients who did not lose body weight pre-diagnosis (n = 117,469), compared with the grade 1 obese, normal weight patients had 35% (95% CI of HR: 1.17, 1.55) significantly higher adjusted mortality risk. However, among patients experiencing weight loss before diagnosis (n = 27,589), BMI at diagnosis was not associated with mortality risk (all p > 0.05). CONCLUSIONS: Weight loss before the diagnosis of T2DM was not associated with the observed increased mortality risk in normal weight patients with T2DM. This emphasises the importance of addressing risk factors post diagnosis for excess mortality in this group.