Long-term incidence of microvascular disease after bariatric surgery or usual care in patients with obesity, stratified by baseline glycaemic status: a post-hoc analysis of participants from the Swedish Obese Subjects study

Abstract

Background: Bariatric surgery is associated with remission of diabetes and prevention of diabetic complications in patients with obesity and type 2 diabetes. Long-term effects of bariatric surgery on microvascular complications in patients with prediabetes are unknown. The aim of this study was to examine the effects of bariatric surgery on incidence of microvascular complications in patients with obesity stratified by baseline glycaemic status.

Methods: Patients were recruited to the Swedish Obese Subjects (SOS) study between Sept 1, 1987, and Jan 31, 2001. Inclusion criteria were age 37-60 years and BMI of 34 kg/m2 or greater in men and 38 kg/m2 or greater in women. Exclusion criteria were identical in surgery and control groups and designed to exclude patients not suitable for surgery. The surgery group (n=2010) underwent gastric bypass (265 [13%]), gastric banding (376 [19%]), or vertical-banded gastroplasty (1369 [68%]). Participants in the control group (n=2037) received usual care. Bodyweight was measured and questionnaires were completed at baseline and at 0·5 years, 1 year, 2 years, 3 years, 4 years, 6 years, 8 years, 10 years, 15 years, and 20 years. Biochemical variables were measured at baseline and at 2 years, 10 years, and 15 years. We categorised participants into subgroups on the basis of baseline glycaemic status (normal [fasting blood glucose concentration <5·0 mmol/L], prediabetes [5·0-6·0 mmol/L], screen-detected diabetes [≥6·1 mmol/L at baseline visit without previous diagnosis], and established diabetes [diagnosis of diabetes before study inclusion]). We obtained data about first incidence of microvascular disease from nationwide registers and about diabetes incidence at study visits at 2 years, 10 years, and 15 years. We did the main analysis by intention to treat, and subgroup analyses after stratification by baseline glycaemic status and by diabetes status at the 15 year follow-up. The SOS study is registered with ClinicalTrials.gov, NCT01479452.

Findings: 4032 of the 4047 participants in the SOS study were included in this analysis. We excluded four patients with suspected type 1 diabetes, and 11 patients with unknown glycaemic status at baseline. At baseline, 2838 patients had normal blood glucose, 591 had prediabetes, 246 had screen-detected diabetes, and 357 had established diabetes. Median follow-up was 19 years (IQR 16-21). We identified 374 incident cases of microvascular disease in the control group and 224 in the surgery group (hazard ratio [HR] 0·56, 95% CI 0·48-0·66; p<0·0001). Interaction between baseline glycaemic status and effect of treatment on incidence of microvascular disease was significant (p=0·0003). Unadjusted HRs were lowest in the subgroup with prediabetes (0·18, 95% CI 0·11-0·30), followed by subgroups with screen-detected diabetes (0·39, 0·24-0·65), established diabetes (0·54, 0·40-0·72), and normoglycaemia (0·63, 0·48-0·81). Surgery was associated with reduced incidence of microvascular events in people with prediabetes regardless of whether they developed diabetes during follow-up.

Interpretation: Bariatric surgery was associated with reduced risk of microvascular complications in all subgroups, but the greatest relative risk reduction was observed in patients with prediabetes at baseline. Our results suggest that prediabetes should be treated aggressively to prevent future microvascular events, and effective non-surgical treatments need to be developed for this purpose.

Funding: US National Institutes of Health, Swedish Research Council, Sahlgrenska University Hospital Regional Agreement on Medical Education and Research, and Swedish Diabetes Foundation.

Conflict of interest statement

Declaration of interests

LMSC has obtained lecture fees from AstraZeneca, Johnson&Johnson, and MSD. KS holds stocks in Pfizer. BC and CK are and SH previously was employed by AstraZeneca and BC, CK and SH all hold stocks in the same company. No other conflict of interest relevant to this study was reported. MN has received lecture and/or consulting fees from Abbott, Sanofi-Aventis, Roche, Itrim International, and Strategic Health Resources; research grants from AstraZeneca and Pfizer (last 5 years).

Copyright © 2017 Elsevier Ltd. All rights reserved.

Figures

Figure 1. Risk factor-treatment interaction analyses for incidence of microvascular events in the SOS study

A: Incidence of first time microvascular events (retinopathy, nephropathy and neuropathy, whichever came first) in high-risk and low-risk subgroups. For continuous variables, subgrouping is based on quartiles of baseline values. B: Risk factor-treatment interactions for microvascular events in subgroups. C: Number needed to treat (NNT) over 10 years to prevent one microvascular event.

Figure 2. Cumulative incidence of microvascular events after bariatric surgery or usual care in subgroups stratified by baseline glucose status

The x-axes are truncated at 20 years but all observations after 20 years were included in the analyses. Euglycemia, normal fasting glucose; Prediabetes, impaired fasting glucose; ST2D, screen-detected type 2 diabetes; T2D, established type 2 diabetes. HR, hazard ratio; HRa, adjusted hazard ratio.

Figure 3. Cumulative incidence of microvascular events after bariatric surgery or usual care in patients with baseline prediabetes stratified by development of type 2 diabetes at or before the 15-year follow-up

The x-axes are truncated at 20 years but all observations after 20 years were included in the analyses. Prediabetes, impaired fasting glucose; Without diabetes, type 2 diabetes not present at or before the 15-year follow-up; With diabetes, type 2 diabetes diagnosed at or before the 15-year follow-up. HR, hazard ratio; HRa, adjusted hazard ratio.