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Open AccessArticle

Association between On-Treatment Haemoglobin A1c and All-Cause Mortality in Individuals with Type 2 Diabetes: Importance of Personalized Goals and Type of Anti-Hyperglycaemic Treatment

by Emanuela Orsi 1, Enzo Bonora 2, Anna Solini 3, Cecilia Fondelli 4, Roberto Trevisan 5, Monica Vedovato 6, Franco Cavalot 7, Gianpaolo Zerbini 8, Susanna Morano 9, Antonio Nicolucci 10, Giuseppe Penno 11 and Giuseppe Pugliese 12,*,† for the Renal Insufficiency and Cardiovascular Events (RIACE) Study Group
1
Diabetes Unit, Fondazione IRCCS “Cà Granda—Ospedale Maggiore Policlinico”, 20122 Milan, Italy
2
Division of Endocrinology, Diabetes and Metabolism, University and Hospital Trust of Verona, 37126 Verona, Italy
3
Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, 56126 Pisa, Italy
4
Department of Medicine, Surgery and Neurosciences, Diabetes Unit, University of Siena, 53100 Siena, Italy
5
Endocrinology and Diabetes Unit, Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, 24127 Bergamo, Italy
6
Department of Clinical and Experimental Medicine, University of Padua, 35128 Padua, Italy
7
Metabolic Diseases and Diabetes Unit, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy
8
Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, 00163 Milan, Italy
9
Department of Experimental Medicine, “La Sapienza” University, 00161 Rome, Italy
10
Centre for Outcomes Research and Clinical Epidemiology (CORESEARCH), 65124 Pescara, Italy
11
Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy
12
Department of Clinical and Molecular Medicine, “La Sapienza” University, Via di Grottarossa 1035-1039, 00189 Rome, Italy
*
Author to whom correspondence should be addressed.
A complete list of the RIACE Investigators can be found in the Supplementary Materials.
J. Clin. Med. 2020, 9(1), 246; https://doi.org/10.3390/jcm9010246
Received: 4 January 2020 / Revised: 13 January 2020 / Accepted: 14 January 2020 / Published: 17 January 2020
(This article belongs to the Section Endocrinology & Metabolism)
The increased mortality reported with intensive glycaemic control has been attributed to an increased risk of treatment-related hypoglycaemia. This study investigated the relationships of haemoglobin (Hb) A1c, anti-hyperglycaemic treatment, and potential risks of adverse effects with all-cause mortality in patients with type 2 diabetes. Patients (n = 15,773) were stratified into four categories according to baseline HbA1c and then assigned to three target categories, based on whether HbA1c was ≤0.5% below or above (on-target), >0.5% below (below-target) or >0.5% above (above-target) their HbA1c goal, personalized according to the number of potential risks among age > 70 years, diabetes duration > 10 years, advanced complication(s), and severe comorbidity (ies). The vital status was retrieved for 15,656 patients (99.26%). Over a 7.4-year follow-up, mortality risk was increased among patients in the highest HbA1c category (≥8.5%) (adjusted hazard ratio, 1.34 (95% confidence interval, 1.22–1.47), p < 0.001) and those above-target (1.42 (1.29–1.57), p < 0.001). Risk was increased among individuals in the lowest HbA1c category (<6.5%) and those below-target only if treated with agents causing hypoglycaemia (1.16 (1.03–1.29), p = 0.01 and 1.10 (1.01–1.22), p = 0.04, respectively). These data suggest the importance of setting both upper and lower personalized HbA1c goals to avoid overtreatment in high-risk individuals with type 2 diabetes treated with agents causing hypoglycaemia. View Full-Text
Keywords: type 2 diabetes; HbA1c all-cause mortality; adverse treatment effects; hypoglycaemia type 2 diabetes; HbA1c all-cause mortality; adverse treatment effects; hypoglycaemia
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Orsi, E.; Bonora, E.; Solini, A.; Fondelli, C.; Trevisan, R.; Vedovato, M.; Cavalot, F.; Zerbini, G.; Morano, S.; Nicolucci, A.; Penno, G.; Pugliese, G., for the Renal Insufficiency and Cardiovascular Events (RIACE) Study Group; Association between On-Treatment Haemoglobin A1c and All-Cause Mortality in Individuals with Type 2 Diabetes: Importance of Personalized Goals and Type of Anti-Hyperglycaemic Treatment. J. Clin. Med. 2020, 9, 246.

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