Currently, there is an exponential increase in the prevalence of type 2 diabetes within the population. For this reason, better ways to treat patients with diabetes are needed. There is evidence that bariatric surgery is an effective form of therapy for patients with type 2 diabetes. However, determining the “best” surgical treatment for diabetes is an important task facing the bariatric surgical community. The optimal procedure should have acceptably low morbidity and mortality, resulting in significant and durable glycemic control. It should also lead to the improvement or resolution of diabetes-related comorbidities, as well as increase quality of life.
The main focus of this report is the comparison of glycemic control outcomes following IT and BPD. We demonstrated that IT provides a significant advantage over BPD when comparing insulin sensitivity and GLP-1. A similar effect with BPD on glycemia, plasma insulin, glucose tolerance and plasma lipids was demonstrated. Both IT and BPD showed sustained effect in the resolution of diabetes. Similar to previous observations, these surgeries achieved normal concentrations of fasting glycemia and fasting plasma insulin,6,7,11,12
restored insulin sensitivity,6,8,21,24
prevented progression in impaired glucose tolerance21,25
and reduced mortality from diabetes.26
In this study, IT yielded a better result than BPD in insulin sensitivity and GLP-1. Moreover, irrespective of the statistical results, animals that underwent IT had a better absolute value in plasma glucose levels and lipid profile than those that underwent BPD. Results in the BPD group suggest that IT shows a superior glycemic control than BPD. Furthermore, we speculate that IT might provide a significantly better result than BPD in further experiments with larger samples. These data give strong evidence that the role of the hindgut in the resolution of diabetes is at least similar, if not more crucial than, bypass of the proximal bowel.
An alternative explanation for our findings is the hypothesis that high levels of plasma GLP-1 reported after jejunoileal bypass27
play a crucial role in the mechanism of diabetes control after bariatric surgery.28,29
Additionally, it has been well-documented that rats with elevated GLP-1 with deletions or mutations in the GLP-1–metabolizing enzyme dipeptidylpeptidase-IV show improved glucose tolerance.30,31
Previous studies have indicated that ileal segments transposed into the duodenojejunal region become extremely hypertrophied after transposition and secrete significantly more enteroglucagon compared with sham-operated rats.32,33
Likewise, the rats that underwent IT showed a significantly increased GLP-1 level over those that underwent BPD or the sham operation in our study. Thus, we speculate that because of the positive effect of IT on GLP-1, IT achieves superior control of diabetes than BPD. The increased GLP-1 levels after IT and BPD suggest that greater production of GLP-1, triggered by the earlier presentation of undigested food in lower segments of the bowel, might be involved in the glycemic control resulting from bypass procedures for the treatment of obesity.28
In the present study, the fact that rats that underwent IT demonstrated lower glucose tolerance but more insulin sensitivity and similar postoperative plasma glucose levels compared with rats that underwent BPD showed that GLP-1 results in the long-term remission of diabetes by improving insulin sensitivity through restoration of insulin signalling.34
Interestingly, it has been demonstrated that the bypass procedure significantly increases GLP-1 levels of morbidly obese nondiabetic patients but not of diabetic patients.35
Moreover, a study of bypass procedures concluded that GLP-1 was not a critical factor for the early changes in glucose tolerance.36
Another study also reported that bypass procedures have been shown to produce substantially increasing GLP-1 levels in obese patients with type 2 diabetes.37
Although the present study did not conclusively assess the effect of bypass procedures on GLP-1 in type 2 diabetes, the possibility of an effect of bypass procedures on GLP-1 is of interest. Increases in signalling pathways are considered to be among the most critical alterations underlying type 2 diabetes,38
in which the incretin-like effect of GLP-1 is characteristically attenuated secondarily to decreased expression of GLP-1 receptors.39
The second issue we tried to address was the comparison of postoperative recovery and complications between IT and BPD. We demonstrated that postoperative recovery in rats that underwent IT was faster than that in rats that underwent BPD. It has been previously shown that rats that underwent IT had no malabsorption problems and needed little postoperative management.40
The easier the procedure, the shorter the postoperative recovery. The present data strongly support this association. Moreover, we found that IT was associated with a shorter duration of surgery (50.82 [SD 8.49] min v. 83.44 [SD 15.26] min; p
< 0.001), faster postoperative recovery (19.29 [SD 7.26] h v. 51.25 [SD 14.7] h; p
< 0.001) and a significant decrease in both major and minor postoperative complications compared with BPD. In contrast, bypass procedure research in humans showed that the overall early complication rate ranges from 3% to 15%,41,42
and because of possible iron and vitamin B12
deficiency, there is a need for long-term supervision and vitamin and mineral replacement.43
Both operations appear to be reasonably safe, with low 30-day mortality, particularly considering that this series includes our initial experience with IT.
These findings are in agreement with the observations published in a series of laparoscopic approaches for bypass procedure documenting an overall mortality of 0.2%41
and a large series documenting a 0.4%–0.8% mortality for BPD.6
This issue is an important point because it indicates that IT is an alternative method of providing long-term control of glycemia and normal levels of insulin with lower mortality compared with BPD.
In addition to providing good glycemic control, the results of both operations presented herein corroborate and extend previous work in several ways. First, both operations appeared to result in stable weight loss compared with a carefully constructed sham surgical procedure (involving transections and anastomoses). Previous research has shown that rats that underwent IT have been able to maintain weight loss and reduced food intake for as long as 6 months after surgery,44
and similar results have been reported in studies of BPD. In our study, the net weight difference of the BPD and IT groups compared with the sham-operated groups was persistent and maintained at more than 70 g 24 weeks after surgery. Second, it has been suggested recently that the low levels of free fatty acids found after BPD might reflect dependence on some degree of fat malabsorption and might have played a role in improving glycemic control.23
In our research, we demonstrated that both operations can effectively lower the levels of free fatty acids compared with the sham operation. Indeed, it has been demonstrated previously that high levels of free fatty acids induce insulin resistance,45
and lowered levels of free fatty acids are associated with improved insulin sensitivity in hyperlipidemic human patients.46
Third, in our study the control of diabetes induced by both IT and BPD was not dependent on the resolution of obesity-related abnormalities because we used a nonobese model. The effect on glucose metabolism seems to be a direct consequence of the duodenal jejunal exclusion and the IT rather than weight loss. Decreased food intake can also be ruled out as a cause because the rate of food ingestion was the same in all study groups, including the sham-operated groups. These findings are consistent with those reported in previous studies in humans that indicated the plasma glucose and insulin levels after bariatric surgery occurred before substantial weight loss.47