Background: This study investigates the associations between changes in serum Triglycerides (S-TG), -Urate (S-Urate), and -Glucose (S-Glu) and changes in serum Calcium (S-Ca), -Magnesium (S-Mg), and -Phosphate (S-P) in patients with type 2 diabetes compared with non-diabetic patients. Methods: The analysis is based on data collected from a secondary prevention population of women and men (W/M) at risk for cardiovascular disease (type 2 diabetes, 212/200; non-diabetes 968/703). The whole population (n = 2083) had a mean age of 51.0 (9.7) years and was stratified for sex and according to type 2 diabetes or non-diabetes. The patients were followed for, either half a year or one year and changes in risk factors were calculated from follow-up to baseline, the time when patients were admitted to the health center. The pattern of relationships was evaluated using a structural equation model. Results: Higher S-TG and S-Glu but lower S-Urate was revealed at baseline in type 2 diabetes women and men as compared to their counterparts, non-diabetes patients. Women with type 2 diabetes had higher S-Ca and lower S-Mg than non-diabetes women. Changes in S-Glu were associated with changes in S-Ca (+), baseline S-Ca (+), and S-Urate (-) in type 2 diabetes men. Changes in S-Urate were associated with changes in S-Mg (+) in type 2 diabetes women and non-diabetes men. In men with non-diabetes, changes in S-Glu were associated with changes in S-Mg (-). In women with non-diabetes, changes in S-Glu were associated with changes in S-P (-) and changes in S-Urate with changes in S-Ca (+). Conclusion: With respect to metabolic disturbances in non-diabetes and the awareness of risk for type 2 diabetes, changes in S-Glu and changes in S-Ca, S-Mg, and S-P should be considered as risk factors for cardiovascular disease. Increased early detection and corrections of high S-Ca, low S-Mg, and S-P in obese patients may improve their metabolism and reduce the risk of CVD in patients with type 2 diabetes. Trial registration number: ISRCTN: ISRCTN79355192