Association between a metabolic syndrome severity score and all- cause mortality in type 1 diabetes: a 10-year follow-up study

Background and aims: The prevalence of distinctive traits of the Metabolic Syndrome (MetS) is increasing among individuals with type 1 diabetes mellitus (T1DM). We have therefore determined in a longitu- dinal study the association between a “MetS severity score” (MetS score; courtesy of Dr. Mark DeBoer) and all-cause mortality in T1DM. Materials and methods: We consecutively recruited 774 T1DM individ- uals (age 40.2 ± 11.7 years; diabetes duration (DD) 19.4 ± 12.2 years; BMI 24.8 ± 3.6 kg/m2; HbA1c 7.8 ± 1.2%) for whom all-cause mortality was assessed over a 10.6 ± 2.6 year follow-up. MetS score was based on waist circumference (WC), systolic blood pressure (sBP), HDL- cholesterol and triglycerides with exclusion of blood glucose. Hazard ratios (HRs) for MetS score stratified by quartiles and all-cause mortality were determined by unadjusted and adjusted Cox regression. Results: Mean MetS score was −0.50 ± 0.67 (mean ± SD; median −0.58; IQR −0.96 to −0.15). After stratification by quartiles, compared to Q1, Q2–4 showed a progressive increase of age, BMI, diastolic blood pres- sure, fasting glucose, HbA1c, total-, LDL- and nonHDL-cholesterol, uric acid and fibrinogen (p < 0.0001). WC, sBP and triglycerides, and ACR also increased, while HDL and eGFR (CKD-EPI) decreased (p = 0.006). A progressive increase was found in percentage of males (p = 0.061), CV events (1.0%, 4.6%, 6.2% and 9.3%; p = 0.003), eGFR <60 ml/min/ 1.73 m2 (p = 0.038), micro- or macroalbuminuria, (p = 0.007), and retinopathy (p = 0.003) as well as use of BP-lowering agents, RAS-blockers, lipid-lowering and anti-platelet drugs (p < 0.0001). A total of 52 deaths occurred during the 8,184 person-years of follow-up (6.7%; 6.36 × 1000 person-years). Death rate increased with MetS score: Q1 2.1%; Q2 5.7% (HR 3.10, 95%CI 0.99–9.75, p = 0.053); Q3 5.7% (2.78, 0.88–8.73, p = 0.080); Q4 13.5% (7.02, 2.45–20.12, p < 0.0001; K-M, Log Rank 21.46, p < 0.0001). Adjusting for age (HR 1.08, 95%CI 1.06–1.11, p < 0.0001) and sex (M, 1.737, 0.98–3.08, p = 0.059), HRs vs Q1 (p = 0.020) were: Q2 2.59 (95%CI 0.82–8.15, p = 0.104); Q3 1.94 (0.61–6.12, p = 0.258); Q4 4.24 (1.46–12.31; p = 0.008). Adjusting for age (p < 0.0001), sex (p = 0.022), DD, BMI, HbA1c, LDL-cholesterol, CVD, retinopathy, eGFR (p = 0.013), ACR (p < 0.001), and prior CV events, HRs vs Q1 (p = 0.047) were: Q2 3.36 (95%CI 1.05–10.76, p = 0.041); Q3 2.21 (95%CI 0.69–7.08, p = 0.352); Q4 4.05 (95%CI 1.39–11.75; p = 0.01). In a fully adjusted model that adds also variables included in the equation (i.e., WC, sBP, triglycerides and HDL), age, sex, eGFR and ACR were independent predictor of death, while HRs of MetS score quartiles (p = 0.056) were: Q2 3.18 (95%CI 0.99–10.19, p = 0.051); Q3 2.11 (95%CI 0.66–6.75, p = 0.211); Q4 3.87 (95%CI 1.33–11.23; p = 0.013). Conclusion: Our results suggest that the MetS score may predict all- cause mortality independent of both other cardiovascular risk factors as well as of the single components of MetS. However, larger studies or meta-analytic approaches combining multiple cohorts will be necessary to confirm this initial observation.