In this population-based real-world study with complete follow-up for median 5.3 years, 74% of individuals with type 2 diabetes treated by RYGB experienced diabetes remission after one year. There was a lower chance of remission with older age, increased diabetes duration and greater severity of diabetes at index date. Twenty-seven per cent of those in remission at 1 year experienced relapse after 5 years. Of importance to patients and healthcare providers, those who underwent RYGB surgery had substantially decreased risk of subsequent microvascular complications and a (not statistically significant) decreased risk of subsequent macrovascular complications as compared with non-operated individuals with type 2 diabetes; successful diabetes remission at 1 year was a clear predictor of fewer microvascular complications. The 30 day risk of readmission due to surgical complications after RYGB was 7.5%, higher than we previously reported among RYGB-operated individuals overall (3.3%) , most likely because type 2 diabetes per se disposes to surgical complications. Surgical short-term mortality was very low (<0.5%).
As Isaman et al have stressed, diabetes remission rates following RYGB reported in the literature vary substantially (25–83%) depending on definition of remission, study duration, choice of statistical analysis, whether or not attrition rates are taken into account and whether the setting is population or clinic based, hampering generalisability of previous results . We deviated from the usual definition of diabetes remission  by counting an individual with HbA1c <42 mmol/mol (<6.0%) and use of metformin only as being in diabetes remission, a definition applied in some RYGB outcome studies previously . Building on the cardioprotective results of metformin observed in the UK Prospective Diabetes Study (UKPDS) , it is clinical practice in Denmark to continue metformin despite observed diabetes remission . This more liberal definition explains the higher remission rates seen in our comparison cohort compared with those reported in previous studies (13–20% vs 0–16%) [12, 13, 16]. On the other hand, we defined type 2 diabetes in our study by use of GLD and not by specific diagnostic criteria. By excluding at baseline RYGB-operated individuals with non-pharmacologically treated type 2 diabetes, which may more likely remit following RYGB, our rates of remission might be lower than those reported in previous studies. Still, our real-world data are largely consistent with previous non-population-based single-centre observations of high 1 year diabetes remission rates [5, 7, 8, 10, 31] and 5 year relapse rates of approximately 30–50% [9, 12, 13]. Most interestingly, our findings of older age, higher HbA1c, longer diabetes duration and pre-operative insulin treatment being associated with lack of remission following RYGB corroborate data from previous cohort studies  and single-centre randomised trials . It seems these remission predictors are consistently observed independently of study type and could be included in a remission scoring system [11, 33]. Overall, our findings add evidence to the importance of regular check-ups following RYGB, despite initial diabetes remission, and also suggest that timing of RYGB is important (i.e. consider RYGB while there are still functional pancreatic beta cells). Interestingly, but without any obvious explanation, we found a trend towards male sex being a positive predictor for diabetes remission; this was also reported by Arterburn et al . Our 5 year prevalent remission rate of 70% concurs with previous findings [5, 34]. Of note, there is evidence that operated individuals not reaching the threshold for diabetes remission (whatever the definition) still display better glycaemic control than non-operated individuals, with less use of GLDs than preoperatively [12, 13, 34]. This aligns with the theory of ‘metabolic memory’ introduced by Coleman et al , suggesting that time spent in diabetes remission following RYGB is not spent in vain when it comes to reducing the risk of subsequent microvascular complications.
An important strength of our study is the inclusion of individuals with type 2 diabetes treated by a single type of bariatric surgery. Furthermore, we present real-world clinical data in a population-based setting, representing 30% of the Danish population. Our data catchment area covers both urban and rural areas, all socioeconomic groups, and all types of hospitals/clinics. Because the Danish healthcare system is state-funded, the individual economy of each patient plays no role in whether or not RYGB is offered. This setting may reduce the selection bias arising from whether or not treatment is chosen, a bias that likely affects every non-randomised study on the effects of RYGB. Our setting also ensures complete follow-up through universally covering registries , in contrast to clinic-based settings where patient attrition may be correlated to treatment failure . Our relatively long follow-up of 5.3 years for micro- and macrovascular events is to our knowledge only surpassed by the SOS study group to date . In contrast to the SOS study, which included all types of bariatric procedures, we did not depend on self-reported outcomes. Regarding diabetes remission, Adams et al presented an even longer follow-up, although that study was based on 88 participants with type 2 diabetes only .
A main limitation of our study was the lack in our registries of individual-level data on BMI, a factor associated with risk of type 2 diabetes and macrovascular complications . In a previous study (N = 1429), BMI in Danish individuals treated by RYGB was 46 kg/m2 at time of surgery and 30 kg/m2 at 4.5 years after surgery . In comparison, the average BMI of a Danish person with type 2 diabetes is approximately 30 kg/m2 . This clearly indicates that our RYGB cohort had a considerably higher BMI than the comparison cohort at baseline, also corroborated by their higher baseline prevalence of cardiovascular disease and usage of blood-pressure-lowering drugs. Any uncontrolled confounding from BMI would therefore likely have led us to underestimate the protective effect of RYGB on diabetes complications, not changing our conclusions. We also lacked data on tobacco use, which may be lower in individuals with high BMI  and thus might have driven the cardiovascular risk estimate in the opposite direction . However, we were able to include data on chronic obstructive pulmonary disease in our analysis; this is a strong marker of smoking and was in fact over-represented in the RYGB cohort. In addition, we do not have full data coverage on HbA1c in every 6 month follow-up period (although better than previous studies of RYGB ), which might limit the interpretation of remission and relapse. Finally, due to a limited number of the individual micro- and macrovascular complications, related both to study size and to the incomplete assessment of changes in for example retinopathy and albuminuria in registries, we lacked statistical power and were unable to calculate adjusted HRs for individual microvascular and macrovascular complications (alternatively, IRRs were reported).
Despite these limitations, our finding of a 47% lower risk of incident microvascular complications (HR 0.53 [95% CI 0.38, 0.73]) following RYGB confirms data from the few previous existing studies. The SOS study reported a 66% reduced risk (HR 0.44 [95% CI 0.34, 0.56]) of microvascular complications in a study of 343 bariatric-operated and 260 non-operated individuals with type 2 diabetes with a median follow-up of 17.6 years . Johnson et al reported a 78% lower risk (HR 0.22 [95% CI 0.09, 0.49]) of microvascular complications when examining 2580 bariatric-operated individuals and 13,371 control individuals, providing 21 months of follow-up in their observational study based on insurance claims . Neither of these outcome studies controlled for diabetes duration or severity markers as we did. Our findings for microvascular complications also corroborate those of a new study by O’Brien et al, reporting an adjusted HR 0.41 [95% CI 0.34, 0.48]) for microvascular complications during a median of 4.3 years follow-up in 4024 individuals treated by bariatric surgery compared with a control group . Data in this study originated from four healthcare databases in the USA; although there was a disenrolment rate of more than 25% in the surgical cohort during follow-up, the study had the strength of also being able to match for baseline BMI. O’Brien et al  found lower risks of diabetic kidney disease, diabetic retinopathy and diabetic neuropathy in the RYGB-operated cohort, while we observed the strongest associations for reduced kidney disease and retinopathy as the main drivers of reduced microvascular complications. Our findings of improved eGFR in the RYGB cohort during the first 5 years of follow-up may be partly due to the RYGB-induced weight and muscle losses and thus not only be reflective of improved renal function. Still, although RYGB may be associated with kidney disease , the overall effect on kidney function appears beneficial, supported by findings on reductions in albuminuria and lower incidence of end-stage renal disease found in other studies [42, 43]. Finally, our finding that among individuals that had undergone RYGB, diabetes remission after 1 year conferred a 57% lower risk of microvascular complications (HR 0.43 [95% CI 0.25, 0.72]) additionally supports treatment by RYGB in the early years of type 2 diabetes, where chance for remission is greater.
When it comes to the effect of RYGB on macrovascular events, the magnitude of reduced risk (HR 0.76 [95% CI 0.49, 1.18]) that we observed during 5.3 years of follow-up—though statistically imprecise—aligns well with results of the observational SOS study reporting 32% reduced risk (HR 0.68 [95% CI 0.54, 0.85])  and was lower than the 61% (HR 0.39 [95% CI 0.29, 0.51]) reduced risk reported by Johnson et al . Again, our ability to adjust for diabetes duration and severity might partly explain the differences in estimates. We observed the strongest association for reduced ischaemic heart disease as the main driver of reduced macrovascular complications, corroborating findings from Eliasson et al  reporting reduced HR of fatal and non-fatal myocardial infarction (HR 0.51 [0.21, 0.91]) in individuals with type 2 diabetes treated by RYGB.
In conclusion, the findings from this study add to the growing body of evidence on effects of bariatric surgery, specifying that RYGB does remit type 2 diabetes and is associated with a reduced risk of microvascular, and possibly macrovascular, complications, also in population-based non-selected cohorts and especially if introducing surgery at an early stage of disease. Predictors of remission success seem to be very consistent in randomised controlled trials, studies of selected cohorts and population-based studies. On the other hand, there is a substantial risk of relapsing into type 2 diabetes, which should be accounted for when advising patients and planning post-surgery care.