Estimated Glucose Disposal Rate as a Predictor of All-Cause Mortality in Type 1 Diabetes—A 10-Year Follow-Up Study
Authors: GAROFOLO MONIA , BERTOLOTTO ALESSANDRA , CAMPI FABRIZIO , LUCCHESI DANIELA , GIUSTI LAURA , SANCHO-BORNEZ VERONICA , DARDANO ANGELA , MICCOLI ROBERTO , PENNO GIUSEPPE , PRATO STEFANO DEL 
Published: June 2018

Insulin resistance (IR) was described in type 1 diabetes (T1D) and is related to higher risk of complications. The association of estimated Glucose Disposal Rate (eGDR), a proxy of IR, to all-cause mortality was assessed in 774 T1D (age 40.2±11.7; DD 19.4±12.2 years; HbA1c 7.8±1.2%) in a follow-up of 10.6±2.5 years. Mean eGDR was 7.52±2.28 mg/kg/min (median 8.29; IQR 5.54-9.31). In agreement with the “Swedish National Diabetes Register” eGDR was stratified in 4 categories: C1: ≥8.0 (n. 424, 54.8%); C2: 6.0-7.99 (n. 125, 16.1%); C3: 4.0-5.99 (n. 149, 19.3%) and C4: &lt;4.0 mg/kg/min (n. 76, 9.8%). Compared to C1, C2-4 showed a worse CV risk profile with increase in age, DD, BMI, WHR, BP, HbA1c, total-, LDL-, nonHDL-Ch and triglycerides (TG), with HDL-Ch reduction (p&lt;0.0001). eGFR (CKD-EPI) decreased, albuminuria (ACR) increased steeply (p&lt;0.0001). Percentages of males (p=0.002), CV events (0.7, 4.8, 13.4 and 15.8%; p&lt;0.0001), eGFR &lt;60 ml/min/1.73m2 (p&lt;0.0001), micro- or macroalbuminuria, (p&lt;0.0001), advanced retinopathy (7.5, 13.9, 28.7 and 37.3%; p&lt;0.0001) increased from C1 to C4, as well treatments for CV risk factors (p&lt;0.0001). A total of 52 deaths occurred in the 8,184 person-years of follow-up (6.7%; 6.36x1000 person-years). Death rate increased with eGDR categories: C1 2.6%; C2 6.4% (HR 2.32, 95% CI 0.93-5.77); C3 11.4% (4.54, 2.12-9.69); C4 21.1% (8.07, 3.74-17.40, p&lt;0.0001). Adjusting for age (HR 1.08, 95% CI 1.05-1.10, p&lt;0.0001) and sex, HRs vs. C1 were: C2 1.53 (95% CI 0.60-3.87); C3 1.97 (0.88-4.44); C4 3.38 (1.48-7.73; p=0.004). Adjusting for age (HR 1.06, 95% CI 1.04-1.09, p&lt;0.0001), sex (M, HR 1.98, 1.10-3.59, p=0.023), eGFR (HR 0.97, 0.96-0.99, p&lt;0.0001), as well DD, BMI, LDL, CVD and statin, HRs were: C2 1.22 (95% CI 0.47-3.17); C3 1.76 (0.78-3.95); C4 2.69 (1.17-6.23; p=0.021). Only adjustment for variables strictly related to IR (HDL, TG, ACR) excludes eGDR as an independent covariate of mortality. In our T1D cohort, eGDR is an uncertain independent predictor of death.

Disclosure
M. Garofolo: None. A. Bertolotto: None. F. Campi: None. D. Lucchesi: None. L. Giusti: None. V. Sancho-Bornez: None. A. Dardano: None. R. Miccoli: None. G. Penno: 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.