Because RYGB typically promotes complete remission of T2DM in severely obese patients,12,17,18
and because mounting evidence indicates that this results from hormonal and metabolic mechanisms beyond just those related to weight loss,19
use of RYGB to treat T2DM in less obese patients is increasingly being considered.20–22
This concept is particularly germane for populations with enhanced risks of diabetes and CVD at lower BMI levels, such as Asian Indians.4–8,11
Accordingly, we examined the effects of RYGB in a series of Indian patients with T2DM and BMI between 22 and 35 kg/m2
. These subjects had BMI levels below the minimal cutoff for bariatric surgery according to the 1991 NIH Consensus Conference,16
but they would generally be deemed overweight or mildly to moderately obese by Indian-specific WHO criteria.5
Our subjects experienced marked, rapid improvements in glycemia, allowing them, without exception, to discontinue all diabetes medications and thereafter manifest non-diabetic FBG and HbA1c levels. This complete remission of diabetes, which had occurred in every subject by 3 months following surgery (typically by only 1 month), was particularly remarkable because the study cohort had relatively severe baseline T2DM. They had a mean duration of known disease of 9 years, poor initial glycemic control (mean pre-operative HbA1c of 10.1%), and insulin usage in 80% of cases (with oral diabetes medications in the remainder). The impressive improvement in glycemic control we observed was accompanied by substantial reductions in other obesity-related co-morbidities, including hypertension and dyslipidemia. These metabolic benefits produced major reductions in predicted CVD risk, including the probabilities of fatal and non-fatal CHD and strokes. Our salutary results were achieved without mortality, significant surgical morbidity, excessive weight loss, or malnutrition, emphasizing the safety and efficacy of RYGB in Indian patients with T2DM and BMI<35 kg/m2.
Although we did not directly compare RYBG in diabetic patients below vs
. above the traditional BMI cutoff of 35 kg/m2
, comparison of our results with historical controls suggests that this operation is at least as effective against diabetes among less obese persons as among patients obese enough to qualify for bariatric surgery under existing NIH guidelines.16
Patients with BMI>35 kg/m2
typically lose ~1/3 of total body weight, experiencing complete T2DM remission in ~84% of cases.12,13,17,18
Although our subjects with BMI<35 kg/m2
lost only ~1/5 of body weight during the follow-up period, they experienced 100% T2DM remission (and all have since remained euglycemic, without weight regain, during the period when this paper was being prepared and reviewed). For patients with BMI>35 kg/m2
, the few whose diabetes does not remit after RYGB are characterized by longer duration of disease, for example >5 years.24
All of our subjects with BMI<35 kg/m experienced complete T2DM remission, despite an average 8.7-year duration of known disease. Our observation that diabetes improves at least as much or more among less obese patients with lesser weight loss, compared to more obese patients with greater weight loss, suggests that weight loss is not the only determinant of T2DM improvement following RYGB and that additional weight-independent anti-diabetes mechanisms are engaged.19
Consistent with this assertion, we found no correlations between the amount of weight lost and the degree of glycemic improvement – i.e., the magnitude of decrease in FBG or HbA1c – or the rapidity of T2DM remission (data not shown).
One of our most important findings was that RYGB markedly improved predicted CVD risk, as calculated with the UKPDS risk engine. Framingham risk scores have also been utilized to predict CVD risk, but this method has important limitations.25
The UKPDS risk equations are specific for T2DM patients, and they correct for glycemic control and Indian ethnicity.23,26
Thus, UKPDS risk predictions should provide more accurate estimates for our study population. Our subjects’ improvement in metabolic parameters additional to glycemia, such as total and HDL cholesterol, are included in UKPDS risk equations, and they contributed to the decrease in CVD risk. It has been demonstrated that in patients with BMI>35 kg/m2
, RYGB reduces predicted CVD risk and actual observed long-term mortality.14,15,27
Our findings extend these observations to show reductions in predicted CVD risk also among patients with BMI<35 kg/m2
, at least in Asian Indians with T2DM.
Our positive findings regarding RYGB in diabetic patients with BMI<35 kg/m2
complement the small extant literature on bariatric surgery performed in less obese patients with metabolic disease. Other preliminary investigations of RYGB in patients with BMI<35 kg/m2
have also found favorable effects on T2DM and dyslipidemia in Chinese21
populations, both of which have relatively high metabolic disease risks. Importantly, as in our cohort, excessive post-RYGB weight loss was not observed in these studies of less obese patients. Early explorations of gastric banding, biliopancreatic diversion, and experimental gastrointestinal operations to treat T2DM among patients with BMI<35 kg/m2
have also reported desirable results,20,28–30
although further studies are required to judge the balance of risks and benefits among these approaches.
Notable limitations of our work include the modest sample size, absence of control groups, and relatively short duration of follow-up. To our knowledge, however, this is the first study to evaluate RYGB as a treatment for T2DM among Asian Indian patients with BMI<35 kg/m2, and we feel that its promising results help justify larger and longer-term investigations in this area.
If corroborated by more definitive clinical trials, our findings would have important implications for diabetes care, at least among persons of Indian descent. Diet, exercise, and medications remain the cornerstones of primary T2DM therapy. However, the long-term adherence and success rates of lifestyle modifications can be disappointing, and despite an ever-increasing armamentarium of pharmacotherapeutics, adequate glycemic control often remains elusive. Moreover, most diabetes medications promote weight gain, and using them to achieve tight glycemic control increases the risk of hypoglycemia. In cases where behavioral and pharmacologic strategies prove insufficient, surgery offers a powerful alternative. Among severely obese patients, RYGB causes profound weight loss and ameliorates virtually all obesity-related co-morbidities, with acceptable surgical mortality and complication rates of <1% and 10–15%, respectively, and decreased long-term mortality.12,14,15,31
Such encouraging results in patients with T2DM and BMI>35 kg/m2
, along with the continuing evolution of minimally invasive techniques with lower risks, have prompted consideration of RYGB in less obese diabetic individuals.20–22
This is of special relevance in populations such as Asian Indians, who accumulate more body fat, especially visceral fat, than Caucasians do at a comparable BMI levels.4–8,11
Our data support the use of RYGB for Indian patients with T2DM and BMI<35 kg/m2
, although independent corroborations of our findings are required before considering widespread changes in clinical practice.