medwireNews: People in different type 2 diabetes subgroups may experience varying levels of improvement after bariatric surgery, with those in the severe insulin-resistant diabetes (SIRD) group most likely to benefit, study findings indicate.
The individuals with SIRD, which is characterized by mild hyperglycemia but marked insulin resistance and hyperinsulinemia plus an increased risk for diabetic nephropathy, had the highest rates of diabetes remission and the greatest improvements in estimated glomerular filtration rate (eGFR) post-surgery when compared with those with mild obesity-related diabetes (MOD) or severe insulin deficient diabetes (SIDD).
Writing in The Lancet Diabetes & Endocrinology, François Pattou (Institut Pasteur de Lille, France) and co-authors say their findings “might represent a step toward the implementation of precision medicine in metabolic surgery.”
Pattou and team applied a recently proposed data-driven, type 2 diabetes classification system to 368 individuals who underwent Roux-en-Y gastric bypass or sleeve gastrectomy in France between 2006 and 2017, and to 121 people who underwent Roux-en-Y gastric bypass in Brazil between 2008 and 2016.
They found that, in the French cohort, 9.2% of participants met the criteria for the SIRD cluster, 85.5% had MOD, 4.6% had SIDD, and 0.8% had severe autoimmune diabetes or mild agerelated diabetes. In the Brazilian cohort, the corresponding proportions were 8.3%, 68.6%, 20.7%, and 2.5%.
At 1-year post surgery, diabetes remission rates were 81% in the French SIRD subgroup and 90% in the corresponding Brazilian subgroup.
For individuals with MOD, the remission rates were 55% in France and 51% in Brazil, while for those with SIDD, the rates were 13% and 36%, respectively.
When the data from the two cohorts were combined, the researchers report that patients with SIRD were a significant 4.3 times more likely to be in diabetes remission at 1-year post surgery than those with MOD or SIDD, after adjustment for age, sex, diabetes duration, BMI, and surgery type.
Pattou and colleagues also used the combined data to analyze postoperative changes in renal function across the three diabetes clusters.
In this case, eGFR increased after surgery among the participants with SIRD, resulting in a decrease in the number of patients with stage 2 or 3 of chronic kidney disease (CKD) at 1 year. For the patients with MOD, eGFR was similar at 1 year to what it was at baseline, while for those with SIDD it decreased slightly. In both groups, the proportion with stage 2 or 3 CKD increased in the year following surgery.
In multivariable analysis, SIRD was associated with a significant increase in eGFR post-surgery, at a mean effect size 13.1 mL/min per 1.73 m2 relative to MOD and SIDD.
Of note, glucose control improved in all three subgroups postsurgery, but the reduction in glycated hemoglobin levels was significantly greater among people with SIDD versus those with SIRD or MOD. Mean BMI fell by 14–18 kg/m2 across the three groups, with no significant difference between them.
Pattou et al conclude: “Our results show the clinical relevance of datadriven classification to inform therapeutic choice, supporting the indication for metabolic surgery in patients with SIRD, and the distinct biological characteristics of this subgroup of patients.”
In an accompanying comment, Jason Flannick, from The Broad Institute of MIT and Harvard, in Cambridge, Massachusetts, USA, says it is unclear how the study findings will translate into clinical practice because “less than 10% of patients with type 2 diabetes fall into the SIRD cluster, and already a very small fraction of patients with type 2 diabetes undergo metabolic surgery.”
He adds: “Moreover, existing scores for predicting successful metabolic surgery perform better than SIRD at predicting post-surgery type 2 diabetes remission (although not, notably, at predicting increases in eGFR).”
In spite of this, Flannick believes “the results of the study suggest that patients with SIRD might share dysfunction of an underlying biological pathway, even if this pathway does not completely explain their disease.”
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Lancet Diabetes Endocrinol 2022; doi:10.1016/S2213-8587(22)00005-5
Lancet Diabetes Endocrinol 2022; doi:10.1016/S2213-8587(22)00034-1