Bariatric Surgery Cuts Microvascular Complications of (Pre)diabetes

Miriam E Tucker

March 07, 2017

Bariatric surgery reduces the risk for microvascular complications, and, interestingly, this happens to an even greater degree among people with prediabetes than in those with diabetes, new results indicate.

The findings come from a post hoc analysis of 4032 of the original 4047 participants from the Swedish Obese Subjects (SOS) study.

After 15 years of follow-up, bariatric surgery was associated with reduced incidence of microvascular complications in those with diabetes, prediabetes, and normal glycemia prior to surgery. However, the largest risk reduction occurred among the prediabetes group.

"I think the most important finding is that prediabetes is a condition that should be treated more aggressively than what we do today to prevent microvascular complications and that metabolic/bariatric surgery is an effective treatment in this group of patients," lead author Lena MS Carlsson, MD, PhD, professor of clinical metabolic research at Sahlgrenska Academy, University of Gothenburg, Sweden, told Medscape Medical News.

She added, "Our conclusion is not that metabolic surgery should be used more widely. However, among obese patients who are considered for bariatric surgery, we think that those with prediabetes should be prioritized because they are at high risk for diabetes and complications, and this can be prevented if they are operated [on]."

Dr Carlsson and colleagues' findings were published online recently in Lancet Diabetes & Endocrinology.

Indeed, in an accompanying editorial, George K Dimitriadis, of the University of Warwick Medical School, Coventry, United Kingdom, and colleagues point out, "Accumulating evidence suggests that prediabetes is not simply a state of abnormal glucose concentration but a prediagnosis of diabetes in which pathophysiological processes constituting microvascular and macrovascular complications might already be present."

Thus, they say that the findings provide support for more clearly defining the criteria for prioritization for bariatric surgery, although they acknowledge "such an approach might be practically challenging considering the large numbers of patients with overt diabetes who are currently undertreated."

Microvascular Complications Reduced in All Surgery Patients

The original SOS study, which began in 1987, included over 4000 patients aged 37 to 60 years with BMIs of 34 kg/m2 or greater in men and 38 kg/m2 or greater in women. Procedures used in those randomized to surgery (n = 2010) were gastric bypass (13%), gastric banding (19%), or vertical banded gastropathy (68%); the latter procedure is no longer used. The controls received usual care for obesity and diabetes at their primary-care settings.

In overall median follow-up of 19 years, 224 incidences of microvascular disease onset were recorded for the surgery group vs 374 among the controls, corresponding to incidence rates of 6.3 vs 10.9 events per 1000 person-years, respectively (hazard ratio [HR], 0.56; P < .0001).

For the current analysis, the subjects were categorized by baseline glycemic status, and the greatest relative reduction in microvascular complications was seen in those with prediabetes. The association persisted after multivariable adjustment for baseline risk factors including age, sex, BMI, blood pressure, urinary albumin excretion, and smoking status.

Incidence of First Microvascular Disease by Treatment Group per Baseline Glycemic Status

Glycemic status Incidence per 1000 person-years HR for microvascular disease P for HR Number needed to treat
Surgery group Control group
Normal (FBG < 5.0 mmol/L) 3.8 5.9 0.63 0.0003 48
Prediabetes (FBG 5.0–6.0 mmol/L) 3.3 17.1 0.18 <0.0001 7
Screen-detected diabetes (FBG ≥ 6.1 mmol/L at baseline visit without previous diagnosis) 10.8 23.3 0.39 0.0003 8
Established diabetes prior to study inclusion 32.9 55.3 0.54 <0.0001 4

FBG=fasting blood glucose

Prediabetes Is a Pathological State

According to Dr Dimitriadis and colleagues, one possible explanation for the findings might be that interventions are most effective when performed early in the disease course: "Patients with normal glucose tolerance benefit less than those with prediabetes, thus confirming that prediabetes is a pathological state."

Unadjusted hazard ratios for prevention of retinopathy with surgery ranged from 0.18 in those with baseline prediabetes to 0.51 with established diabetes (both P < .0001). For nephropathy, the results for surgery were significant only for those with prediabetes (HR, 0.29; P < .0001) and established diabetes (HR, 0.47; = .0019). And for neuropathy, which was rare, surgery significantly reduced the incidence only among those with prediabetes (P = .0012).

And among those with baseline prediabetes, 55% of the controls (158) vs 16% of the surgery group (47) developed diabetes by year 15.

The incidence of microvascular complication was lower among those in the surgery group, whether or not they developed diabetes.

"Our results were obtained in spite of the fact that older [surgical] methods were used," Dr Carlsson told Medscape Medical News. "New methods have been introduced because they are regarded as better than the older methods, and I therefore expect the results to be similar with modern surgical procedures."

Surgery for Prediabetes, or Something Else?

Dr Dimitriadis and colleagues say that randomized controlled trials are needed to compare complication rates following metabolic (the term increasingly used instead of "bariatric") surgery with nonsurgical interventions among patients with glycemia ranging from normal to prediabetes to diabetes.

"Such trials would require substantial funding and international collaborations but would provide invaluable evidence to guide the clinical management of patients across the spectrum of glucose homeostasis," they say.

Dr Carlsson believes the findings suggest a rethinking of the glycemic cutoffs used to define diabetes.

"I think we should be more careful when using the threshold, because prediabetes and diabetes represent different progressive stages of the same disease," she said, noting that the cutoffs for diabetes were originally chosen based on the level of glucose at which microvascular disease occurred in cross-sectional data, whereas the current study examines longitudinal intervention data.

"Our data show that long-term exposure to prediabetic glucose is harmful because it leads to microvascular disease. We also show that it is possible to prevent this with bariatric surgery."

However, she also recognizes that "it will not be possible to operate on all obese patients who have prediabetes. However, nonsurgical methods have not been successful in terms of prevention of microvascular disease in prediabetes. Better nonsurgical treatments therefore need to be developed."

The study was supported by grants from the US National Institute of Diabetes and Digestive and Kidney Diseases, the Swedish Research Council, Sahlgrenska University Hospital Regional Agreement on Medical Education and Research, and the Swedish Diabetes Foundation. Dr Carlsson has received lecture fees from AstraZeneca, Johnson & Johnson, and Merck Sharp & Dohme. Disclosures for the coauthors are listed in the paper. The editorialists have no relevant financial relationships.

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Lancet Diabetes Endocrinol. Published online February 22, 2017. Abstract

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