Independent Association of a Metabolic Syndrome Severity Score with All-Cause Mortality in Type 1 Diabetes—A 10-Year Follow-Up
Authors: PENNO GIUSEPPE , GAROFOLO MONIA , GIANNARELLI ROSA , CAMPI FABRIZIO , LUCCHESI DANIELA , GIUSTI LAURA , SANCHO-BORNEZ VERONICA , DARDANO ANGELA , DANIELE GIUSEPPE , MICCOLI ROBERTO , DEL PRATO STEFANO 
Published: June 2018

Metabolic Syndrome (MetS) is identified by dichotomous criteria thus masking MetS-related risk exists as a continuum. We assessed the association of a “MetS severity score” (MSs; courtesy Dr. M. DeBoer) with all-cause death in 774 T1D (age 40.2±11.7; DD 19.4±12.2 years; HbA1c 7.8±1.2%) over a 10.6±2.5 year follow-up. MSs was derived from WC, sBP, HDL and triglycerides (no glucose). Mean MSs was -0.5046±0.6717 (median -0.5820; IQR -0.9556 to -0.1529). MSs was stratified by quartiles. Compared to Q1, Q2-4 had a worse CV risk profile with increasing age, BMI, dBP, fasting glucose, HbA1c, total-, LDL- and nonHDL-Ch, uric acid and fibrinogen (p&lt;0.0001). As expected, WC, sBP and triglycerides increased, while HDL decreased (p&lt;0.0001). eGFR was steeply lower (p=0.006), ACR steeply higher (p=0.005). With MSs, rate of CV events (1.0, 4.6, 6.2 and 9.3%; p=0.003), eGFR &lt;60 ml/min/1.73m2 (p=0.038), ACR strata (p=0.007) and retinopathy (p=0.003) increased. A total of 52 deaths occurred during the 8,184 person-years of follow-up (6.7%; 6.36x1000 person-years). Death rate increased with MSs: Q1 2.1%; Q2 5.7% (HR 3.10, 95% CI 0.99-9.75); Q3 5.7% (2.78, 0.88-8.73); Q4 13.5% (7.02, 2.45-20.12; p&lt;0.0001). Adjusting for age (HR 1.08, 95% CI 1.06-1.11, p&lt;0.0001) and sex (M, p=0.059), HRs vs. Q1 were: Q2 2.59 (95% CI 0.82-8.15); Q3 1.94 (0.61-6.12); Q4 4.24 (1.46-12.31; p=0.008). Adjusting for age (p&lt;0.0001), sex (p=0.022), DD, BMI, HbA1c, LDL, CVD, retinopathy, eGFR (p=0.013) and ACR (p&lt;0.001), HRs vs. Q1 were: Q2 3.36 (95% CI 1.05-10.76, p=0.041); Q3 2.21 (0.69-7.08); Q4 4.(1.39-11.75; p=0.01). In fully adjusted model for variables included in the equation, age, sex, eGFR and ACR were independent predictor of death, while HRs vs. Q1 (p=0.056) were: Q2 3.18 (95% CI 0.99-10.19, p=0.051); Q3 2.11 (0.66-6.75); Q4 3.87 (1.33-11.23; p=0.013). In individuals with T1DM, the highest MetS scores predict all-cause mortality indipendent of other CV risk factors and single components of MetS.

Disclosure
G. Penno: None. M. Garofolo: None. R. Giannarelli: None. F. Campi: None. D. Lucchesi: None. L. Giusti: None. V. Sancho-Bornez: None. A. Dardano: None. G. Daniele: None. R. Miccoli: None. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Servier, Sanofi, Takeda Pharmaceuticals U.S.A., Inc.. Research Support; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Takeda Pharmaceuticals U.S.A., Inc.. Advisory Panel; Self; Janssen Biotech, Inc., Abbott.