Prediction of Type 2 Diabetes Remission at Long-term Following Biliopancreatic Diversion: the Relative Role of Different Metabolic Attitudes

Abstract

In type 2 diabetic (T2DM) obese patients, recent randomized and controlled trials have confirmed that, in achieving and maintaining glycemic control, metabolic/bariatric surgery is far more efficient than the traditional pharmacological conservative therapies [1]. Furthermore, metabolic/bariatric surgery beneficial effects are not limited to blood glucose control: after the operation, dyslipidemia tends to disappear, arterial hypertension subsides towards normality, the occurrence of cardiovascular diseases decreases, and the overall mortality risk reduces [2]. On the other hand, bariatric/metabolic operations are challenging and highly demanding procedures that cannot be proposed to all T2DM obese patients. For these reasons, it is clinically relevant to identify preoperative parameters aimed to predict a good metabolic outcome after surgery and then a true advantage for any single individual. Several parameters have been proposed as a predictor of T2DM remission after a different kind of surgery, including BMI, type of operation, duration of diabetes, use of insulin, C peptide levels, younger age, and HbA1c level [3, 4]. Studies on the topic have demonstrated that many parameters appeared to be good predictors of short-term postoperative T2DM remission, while at a long time the correlation between preoperative data and postoperative metabolic outcomes weakens, as it is suggested by ROC curves showing sensitivity and specificity near to 50% [5, 6]. Since T2DM is a chronic disease, predicting efficacy on a metabolic outcome in the short term is of little clinical value. To develop a better predictor that can preoperatively identify subjects who will benefit from metabolic/bariatric surgery for diabetes, a multicentric prospective investigation will be carried out in a large cohort of obese patients with type 2 diabetes undergoing Roux-en-Y gastric bypass [7]. In this scenario, diabetes remission 10 years after biliopancreatic diversion (BPD) is observed quite more frequently in patients with a preoperative diabetes duration within 1 year, while among those with a T2DM duration longer than 5 years, nearly 30% still require insulin therapy [8]. This data strongly suggests a critical role of diabetes duration on true T2DM remission. It can be admitted that patients with obesity have a greater than normal beta cell mass [9]. Just in the first months after BPD, prompt postoperative restoration of early insulin secretion after intravenous glucose load has been observed, thus suggesting a full recovery of insulin action that is most likely due to the reduced environmental glycoand lipo-toxicity on the beta cells [10]. In patients with longer T2DM duration, a time-dependent reduction of beta-cell mass can be hypothesized: this could account for the relatively high T2DM longterm recurrence rate observed in this subset of operated patients. However, the diabetes duration, despite the evident influence on the long-term postoperative metabolic outcome, is nearly devoid of predicting efficacy: while short diabetes duration taps all successful outcomes, a long duration identifies only a minority of unsuccessful cases [8]. In the T2DM patients with overweight or mild obesity undergoing BPD, early insulin secretion is not rescued [11], thus suggesting a lack of functioning beta cells, due to a combination of genetic and environmental factors. Therefore, the observed postoperative metabolic improvements are substantially due to decreased insulin resistance. Since as a rule the amount of weight loss is closely related to the initial degree of obesity, the strong positive correlation between diabetes remission and initial BMI is not surprising [12]. However, in this cohort of T2DM patients, the predicting efficacy of preoperative BMI values on the steady blood glucose normalization at 5 years following BPD was only weak, being both * Gian Franco Adami [email protected]