Obesity paradox in people newly diagnosed with type 2 diabetes with and without prior cardiovascular disease

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>To address the debate on ‘obesity paradox’ in patients with type 2 diabetes mellitus (<jats:styled-content style="fixed-case">T2DM</jats:styled-content>) by evaluating the cardiovascular and mortality risks associated with normal and overweight patients compared to obese at diagnosis of diabetes, separately for patients with and without cardiovascular disease (<jats:styled-content style="fixed-case">CVD</jats:styled-content>) before diagnosis.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A retrospective study with two study cohorts with/without prior <jats:styled-content style="fixed-case">CVD</jats:styled-content> (n = 10237/37272) with complete measures of body mass index (<jats:styled-content style="fixed-case">BMI</jats:styled-content>) at diagnosis of <jats:styled-content style="fixed-case">T2DM</jats:styled-content> from <jats:styled-content style="fixed-case">UK</jats:styled-content> General Practice Research Database. Primary outcomes were long‐term risks of cardiovascular events (<jats:styled-content style="fixed-case">CVEs</jats:styled-content>) and all‐cause mortality in patients with normal weight, overweight and obesity at diagnosis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The mortality rates per 1000 person‐years in normal weight, overweight and obese patients among patients without prior <jats:styled-content style="fixed-case">CVD</jats:styled-content> were 13.1, 8.6 and 6.0, respectively, during 5 years of median follow‐up. For patients with prior <jats:styled-content style="fixed-case">CVD</jats:styled-content>, these estimates were 30.1, 21.1 and 15.5, respectively. Among patients without and with prior <jats:styled-content style="fixed-case">CVD</jats:styled-content>, normal weight patients had 47% (hazard ratio, <jats:styled-content style="fixed-case">HR CI</jats:styled-content>: 1.29, 1.69) and 30% (<jats:styled-content style="fixed-case">HR CI</jats:styled-content>: 1.11, 1.53) increased mortality risk respectively compared to obese patients. In the cohort without prior <jats:styled-content style="fixed-case">CVD</jats:styled-content>, compared to obese patients, those with normal body weight did not have increased <jats:styled-content style="fixed-case">CVE</jats:styled-content> risk. Interactions between age, <jats:styled-content style="fixed-case">HbA1c</jats:styled-content> and <jats:styled-content style="fixed-case">BMI</jats:styled-content> at diagnosis were observed in both cohorts.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Adults with normal weight at the diagnosis of <jats:styled-content style="fixed-case">T2DM</jats:styled-content> have significantly higher mortality risk compared to those who are obese, with significant interactions between age, <jats:styled-content style="fixed-case">BMI</jats:styled-content> and <jats:styled-content style="fixed-case">HbA1c</jats:styled-content>. Elevated cardiovascular risk was not observed in normal weight patients without prior <jats:styled-content style="fixed-case">CVD</jats:styled-content>.</jats:p></jats:sec>