['In overweight-related hypertension, the effect of weight changes on blood pressure (BP) is believed to be mediated by insulin. To test this hypothesis, we studied 5-year changes in weight, BP, and insulin in a general population of Danish adults (n\u200a=\u200a3443; mean age 45.7\u200a±\u200a7.6 years).', 'We assessed the glucose-insulin metabolism by a standard oral glucose tolerance test. We divided the antihypertensive and antidiabetic medication-free participants into three groups: weight loss (n\u200a=\u200a515), weight stable (n\u200a=\u200a1778), and weight gain (n\u200a=\u200a1150).', 'Losing on average 6.5\u200akg body weight, the weight loss group experienced a 28.2% reduction [(95% confidence interval [CI] -31 to -25); P\u200a<\u200a0.001] in fasting insulin and a 23.9% reduction [(95% CI -28 to -19); P\u200a<\u200a0.001] in 2-h insulin. Gaining on average 6.4\u200akg, the weight gain group experienced a 12.5% increase [(95% CI 9 to 16); P\u200a<\u200a0.001] in fasting insulin and 32.8% increase [(95% CI 28 to 38); P\u200a<\u200a0.001] in 2-h insulin. Using linear regression adjusting for differences in sex, age, family history of hypertension, baseline BMI, SBP and DBP, lifestyle risk factors, and their 5-year changes, weight loss was associated with a decrease in SBP of -1.8\u200ammHg (95% CI -2.8 to -0.7), whereas weight gain with an increase in SBP of 1.9\u200ammHg (95% CI 1.2 to 2.6), both with P less than 0.001. Adding fasting insulin, 2-h insulin, Δfasting insulin, and Δ2-h insulin only marginally attenuated the association, and furthermore, none of the insulin variables was significantly associated with SBP or DBP (P\u200a≥\u200a0.08). The results for changes in DBP were similar to SBP.'] Do five-year weight changes associate with blood pressure alterations independent of changes in serum insulin?