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.
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).
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).
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
Agence Nationale de la Recherche, Investissement d’Avenir, Innovative Medecines Initiative,
Fondation Cœur et Artères, and Fondation Francophone pour la Recherche sur le Diabète.