Violeta Raverdy1, Ricardo V Cohen2, Robert Caiazzo3, Helene Verkindt3, Tarissa Beatrice Zanata Petry2, Camille Marciniak3, Benjamin Legendre1, Pierre Bauvin1, Estelle Chatelain4, Alain Duhamel5, Elodie Drumez5, Naima Oukhouya-Daoud3, Mikael Chetboun3, Gregory Baud3, Emma Ahlqvist6, Niels Wierup6, Olof Asplund6, Blandine Laferrère7, Leif Groop8, FranÇois Pattou9. 1. University Lille, INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, Lille, France. 2. The Center for the Treatment of Obesity and Diabetes, Oswaldo Cruz German Hospital, São Paulo, Brazil. 3. University Lille, INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, Lille, France; CHU Lille, Integrated Center for Obesity, General and Endocrine Surgery, Lille, France. 4. University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41-UMS 2014-PLBS, Bilille, Lille, France. 5. CHU Lille, University Lille, ULR 2694-METRICS: Évaluation des technologies de santé et des pratiques médicales, Lille, France. 6. Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden. 7. Diabetes Research Center, Division of Endocrinology, Department of Medicine, Columbia University, New York City, NY, USA. 8. Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden; Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland. 9. University Lille, INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, Lille, France; CHU Lille, Integrated Center for Obesity, General and Endocrine Surgery, Lille, France. Electronic address: francois.pattou@univ-lille.fr.
Abstract
BACKGROUND: A novel data-driven classification of type 2 diabetes has been proposed to personalise anti-diabetic treatment according to phenotype. One subgroup, severe insulin-resistant diabetes (SIRD), is characterised by mild hyperglycaemia but marked hyperinsulinaemia, and presents an increased risk of diabetic nephropathy. We hypothesised that patients with SIRD could particularly benefit from metabolic surgery. METHODS: We retrospectively related the newly defined clusters with the response to metabolic surgery in participants with type 2 diabetes from independent cohorts in France (the Atlas Biologique de l'Obésite Sévère [ABOS] cohort, n=368; participants underwent Roux-en-Y gastric bypass or sleeve gastrectomy between Jan 1, 2006, and Dec 12, 2017) and Brazil (the metabolic surgery cohort of the German Hospital of San Paulo, n=121; participants underwent Roux-en-Y gastric bypass between April 1, 2008, and March 20, 2016). The study outcomes were type 2 diabetes remission and improvement of estimated glomerular filtration rate (eGFR). FINDINGS: At baseline, 34 (9%) of 368 patients, 314 (85%) of 368 patients, and 17 (5%) of 368 patients were classified as having SIRD, mild obesity-related diabetes (MOD), and severe insulin deficient diabetes (SIDD) in the ABOS cohort, respectively, and in the São Paulo cohort, ten (8%) of 121 patients, 83 (69%) of 121 patients, and 25 (21%) of 121 patients were classified as having SIRD, MOD, and SIDD, respectively. At 1 year, type 2 diabetes remission was reported in 26 (81%) of 32 and nine (90%) of ten patients with SIRD, 167 (55%) of 306 and 42 (51%) of 83 patients with MOD, and two (13%) of 16 and nine (36%) of 25 patients with SIDD, in the ABOS and São Paulo cohorts, respectively. The mean eGFR was lower in patients with SIRD at baseline and increased postoperatively in these patients in both cohorts. In multivariable analysis, SIRD was associated with more frequent type 2 diabetes remission (odds ratio 4·3, 95% CI 1·8-11·2; p=0·0015), and an increase in eGFR (mean effect size 13·1 ml/min per 1·73 m2, 95% CI 3·6-22·7; p=0·0070). INTERPRETATION: Patients in the SIRD subgroup had better outcomes after metabolic surgery, both in terms of type 2 diabetes remission and renal function, with no additional surgical risk. Data-driven classification might help to refine the indications for metabolic surgery. FUNDING: Agence Nationale de la Recherche, Investissement d'Avenir, Innovative Medecines Initiative, Fondation Cœur et Artères, and Fondation Francophone pour la Recherche sur le Diabète.
BACKGROUND: A novel data-driven classification of type 2 diabetes has been proposed to personalise anti-diabetic treatment according to phenotype. One subgroup, severe insulin-resistant diabetes (SIRD), is characterised by mild hyperglycaemia but marked hyperinsulinaemia, and presents an increased risk of diabetic nephropathy. We hypothesised that patients with SIRD could particularly benefit from metabolic surgery. METHODS: We retrospectively related the newly defined clusters with the response to metabolic surgery in participants with type 2 diabetes from independent cohorts in France (the Atlas Biologique de l'Obésite Sévère [ABOS] cohort, n=368; participants underwent Roux-en-Y gastric bypass or sleeve gastrectomy between Jan 1, 2006, and Dec 12, 2017) and Brazil (the metabolic surgery cohort of the German Hospital of San Paulo, n=121; participants underwent Roux-en-Y gastric bypass between April 1, 2008, and March 20, 2016). The study outcomes were type 2 diabetes remission and improvement of estimated glomerular filtration rate (eGFR). FINDINGS: At baseline, 34 (9%) of 368 patients, 314 (85%) of 368 patients, and 17 (5%) of 368 patients were classified as having SIRD, mild obesity-related diabetes (MOD), and severe insulin deficient diabetes (SIDD) in the ABOS cohort, respectively, and in the São Paulo cohort, ten (8%) of 121 patients, 83 (69%) of 121 patients, and 25 (21%) of 121 patients were classified as having SIRD, MOD, and SIDD, respectively. At 1 year, type 2 diabetes remission was reported in 26 (81%) of 32 and nine (90%) of ten patients with SIRD, 167 (55%) of 306 and 42 (51%) of 83 patients with MOD, and two (13%) of 16 and nine (36%) of 25 patients with SIDD, in the ABOS and São Paulo cohorts, respectively. The mean eGFR was lower in patients with SIRD at baseline and increased postoperatively in these patients in both cohorts. In multivariable analysis, SIRD was associated with more frequent type 2 diabetes remission (odds ratio 4·3, 95% CI 1·8-11·2; p=0·0015), and an increase in eGFR (mean effect size 13·1 ml/min per 1·73 m2, 95% CI 3·6-22·7; p=0·0070). INTERPRETATION: Patients in the SIRD subgroup had better outcomes after metabolic surgery, both in terms of type 2 diabetes remission and renal function, with no additional surgical risk. Data-driven classification might help to refine the indications for metabolic surgery. FUNDING: Agence Nationale de la Recherche, Investissement d'Avenir, Innovative Medecines Initiative, Fondation Cœur et Artères, and Fondation Francophone pour la Recherche sur le Diabète.
Authors: Mara Suleiman; Lorella Marselli; Miriam Cnop; Decio L Eizirik; Carmela De Luca; Francesca R Femia; Marta Tesi; Silvia Del Guerra; Piero Marchetti Journal: Int J Mol Sci Date: 2022-07-04 Impact factor: 6.208