Effects of weight loss and weight gain on HbA1c, systolic blood pressure and total cholesterol in three subgroups defined by blood glucose: a pooled analysis of two behavioural weight management trials in England

OBJECTIVES: To estimate the association between weight and cardiometabolic risk factors across subgroups of individuals with normoglycaemia, non-diabetic hyperglycaemia and type 2 diabetes (T2D) and to explore whether the association differs between weight loss and weight gain. DESIGN: Observational analysis using mixed-effects regression models of pooled trial data. PARTICIPANTS: The Weight loss Referral for Adults in Primary care (n=1267) and Glucose Lowering through Weight management (n=577) trials recruited individuals with overweight or obesity (body mass index, BMI >25 kg/m2) from primary care practices across England. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures were the relationships between a change in (BMI; kg/m2) and a change in glycated haemoglobin (HbA1c; mmol/mol), total cholesterol (mmol/L) or systolic blood pressure (SBP; mm Hg) across three subgroups of individuals with: normoglycaemia, non-diabetic hyperglycaemia and T2D. Secondary outcomes included the influence of weight loss versus weight gain on these relationships. RESULTS: HbA1c is positively related to a change in BMI, and a 1 kg/m2 change was related to a 1.5 mmol/mol (95% CI: 1.1 to 1.9) change in HbA1c in individuals with T2D, 0.6 mmol/mol (95% CI: 0.4 to 0.8) change in those with non-diabetic hyperglycaemia and 0.3 mmol/mol (95% CI: 0.2 to 0.4) change in those with normoglycaemia. In individuals with normoglycaemia, weight gain has a larger impact on HbA1c than weight loss, with a 0.5 mmol/mol (95% CI: 0.3 to 0.7) increase per 1 kg/m2 gained, compared with a relationship that is 0.3 mmol/mol smaller (95% CI: -0.6 to -0.1) per 1 kg/m2 of weight loss. BMI reduction improved SBP and total cholesterol significantly; however, effects did not differ between the three subgroups. CONCLUSIONS: Cardiometabolic risk factors are associated with changes in weight. The association with HbA1c varies by diabetes status, with increasing magnitude in those with non-diabetic hyperglycaemia and T2D. Weight gain has a larger impact on HbA1c than weight loss in individuals with normoglycaemia, implying an asymmetric relationship.