Relationship between degree of risk factor control and all-cause mortality in individuals with type 2 diabetes: A prospective cohort study.

Aims: To assess whether and to what extent excess risk of all-cause death is reduced in individuals with type 2 diabetes by achieving optimal control of traditional cardiovascular risk factors.
Methods: This observational, prospective, cohort study enrolled 15,773 Caucasian patients in 19 Italian centres in 2006-2008. Participants were stratified according to the number of the following risk factors outside target: haemoglobin A _1c , blood pressure, micro/macroalbuminuria, current smoking, LDL cholesterol, and triglycerides. All-cause mortality was retrieved for 15,656 patients (99.3 %) on 31 October 2015.
Results: Age-adjusted mortality rates and hazard ratios were significantly higher in the whole RIACE cohort (by ∼20 %) and in patients with (by ∼100 %) but not in those without prior cardiovascular disease (CVD), as compared with the coeval Italian general population. In all patients and in those without prior CVD, the relationship with mortality according to the number of risk factors outside target was J-shaped, an effect that was attenuated after either excluding "overtreated " patients, i.e., those with haemoglobin A _1c ≤6.0 % on anti-hyperglycaemic agents causing hypoglycaemia and/or systolic blood pressure ≤120 mmHg on anti-hypertensive agents, or adjusting for "overtreatment". Conversely, in patients with prior CVD, mortality remained higher than in the general population in all categories and increased progressively from +70 % to +314 %, without J-effect.
Conclusions: In patients with type 2 diabetes, optimal treatment of traditional cardiovascular risk factors completely eliminated the excess mortality risk versus the general population, provided that they were not "overtreated". However, this effect was observed only in participants without history of CVD.
Trial Registration: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July 2008.
Competing Interests: Declaration of Competing Interest Monia Garofolo: consultant fees from Eli Lilly, and lecture fees from Eli Lilly, Merck Sharp & Dohme, and Novo Nordisk. Giuseppe Penno: consultant fees from Bayer and Eli Lilly, and lecture fees from AstraZeneca, Boerhinger Ingelheim, Eli-Lilly, Merck Sharp & Dohme, Mundipharma, Novo Nordisk, and Takeda. Anna Solini: consultant fees from Axxam, Bayer, and Novo Nordisk, and lecture fees from Eli Lilly, Novo Nordisk, and Sanofi-Aventis. Emanuela Orsi: consultant fees from Eli Lilly and Novo Nordisk, and lecture fees from Astellas. Martina Vitale: lecture fees from MundiPharma and Novo Nordisk. Veronica Resi: lecture fees from Astra-Zeneca, Eli Lilly, and Sanofi-Aventis. Enzo Bonora: consultant fees from Abbott, Bayer, Becton Dickinson, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, and Novo Nordisk. Cecilia Fondelli: lecture fees from Abbot, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Merck Sharp & Dohme, Mundipharma, and Theras Lifetech. Roberto Trevisan: consultant fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, and Sanofi-Aventis, and lecture fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. Monica Vedovato: lecture fees from Lifescan and Novo Nordisk. Antonio Nicolucci: consultant fees from AstraZeneca, lecture fees from Eli Lilly, Medtronic, and Novo Nordisk, and grant support from AlfaSigma, Novo Nordisk, Pikdare, Sanofi, Shionogi, SOBI, and Theras. Giuseppe Pugliese: consultant fees from Abbot, Bayer, and Novo Nordisk, and lecture fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Mundipharma, and Novo Nordisk.
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