Bariatric Times - December 2008 - (Page 15)

Bariatric Times • December 2008 Diabetes Perspective 15 the distal intestine in both RYGB and BPD. Eventually, amelioration of T2DM can be accounted for by the well-known effect of weight loss to increase insulin sensitivity, thereby decreasing glucotoxicity and lipotoxicity and improving βcell function; but, again, T2DM remission usually occurs days or weeks after RYGB or BPD. So, if T2DM resolution occurs long before considerable weight loss, it is long-lasting. So why not offer it to lower BMI patients? Potential mechanisms for glycemic control. Regardless of the molecular explanation, which still remains to be elucidated, it is very important to understand which part of the typical anatomical rearrangement of RYGB/BPD is essential for the resolution effect on diabetes. Two mechanisms have been proposed, based on some elegant animal studies. The foregut or upper intestinal mechanism6-7 holds that the exclusion of the duodenum and proximal jejunum from the transit of nutrients may prevent the secretion of a putative signal that promotes insulin resistance and leads to T2DM control. An alternative proposal, the hindgut or distal intestinal mechanism,8 justifies T2DM remission that results from the expedited delivery of nutrient chyme to the distal intestine, enhancing a physiologic signal that improves glucose metabolism. A potential candidate mediator of this effect is GLP-1 and/or other distal gut peptides. Although no obvious candidate molecules can be identified with current knowledge, if proven true, those theories might open new avenues in the search for the cause and cure of diabetes. Recently, a French group conducted an animal study9 that compared the effects of two types of surgery, a purely restrictive procedure (gastric banding) and duodenal exclusion, on T2DM control. The duodenal exclusion group specifically reduced food intake and increased insulin sensitivity as measured by endogenous glucose production. Intestinal gluconeogenesis increased after the duodenal exclusion procedure, but not after gastric banding. This provides mechanistic evidence that rearranging the upper gut anatomy produces a beneficial effect on food intake and glucose homeostasis involving intestinal gluconeogenesis independent of GLP1 levels or weight change. The study considered an important hepatoportal sensoring pathway. CURE, CONTROL, OR REMISSION? T2DM has a very complex pathophysiology. It includes inadequate hepatic glucose production, genetics, pancreatic amyloid deposition, insulin resistance, and lack of incretin effect through several mechanisms. It is very difficult to fully understand all mechanisms related to how surgery may contribute to improve T2DM. The term cure should never be used when describing the postoperative outcomes. Control or remission are more appropriate. Surgery, as all in other forms of treatment, should be interpreted as complementary and not exclusive therapies. It should never be forgotten that some drugs and even insulin may be very helpful in achieving T2DM control, mainly in the early postoperative period. Among them, metformin, pioglitazone, and sulphonylureas may be necessary to help mantain good blood glucose levels. RECENT HUMAN REPORTS Duodenal jejunal bypass (DJB). A case report by Cohen et al10 published in early 2007—a step toward extending animal studies’ findings into the clinical arena— reported two cases of patients with diabetes who underwent DJB. The patients were overweight or mildly obese, with BMIs of 29 and 30.3kg/m2. Their diabetes was not particularly longstanding (2 and 7 years, respectively), and was treated before surgery with insulin plus metformin in one case and with rosiglitazone in the other. Although no preoperative laboratory data were shown, evaluations at one week, one month, and thereafter at monthly intervals for nine months demonstrated rapid and unequivocal improvements in several simple measures of glucose control. Fasting blood sugars were initially in the diabetic range (148 and 178mg/dL), but they decreased steadily after surgery, reaching nondiabetic values by one month and remaining at 100mg/dL throughout postoperative Months 3 through 9. Similarly, fasting insulin levels started high (27 and These patients underwent laparoscopic RYGB and all had remission of their diabetes. The final common pathway of current and past surgical experience with regard to diabetes resolution seems to be duodenal bypass, although there is some degree of swifter food delivery to 29mmol/L) but declined quickly and progressively after surgery, remaining at levels typical of persons without diabetes (approximately 5mmol/L) throughout postoperative Months 3 through 9. Reflecting the improvement in glycemia, hemoglobin A1c values fell from diabetic (8%–9%) to normal (5%–6%) values by three months, and they remained equally low thereafter during the remaining six months of observation. One patient was discharged a few days after surgery without any diabetes medications and the other had discontinued diabetes medications by five weeks after surgery. In short, both patients converted from having poorly controlled diabetes, despite being on medications, to having normoglycemia and being off of all such medications. A key finding was that this salutary transformation occurred with no weight loss in either patient. At our facility, we continue to enroll patients in our investigational study. So far, nearly 90 patients have submitted to DJB, with BMI ranging from 22 to 34. Those who have had a longer follow-up, from 9 to 12 months, have shown 78-percent full remission or improvement of T2DM, regardless of weight loss or gain. There is no doubt that these findings are a strong paradigm shift in the treatment of patients with diabetes. In this series, there have been strong responders—patients without either insulin or medications who actually regained weight after surgery but are still diabetes-free, with no significant increase of GLP-1 levels. There are several unanswered questions in the mechanism of action of diabetes control after rearranging the upper gastrointestinal anatomy. Recently, we performed a “sleeved duodenal exclusion” in 17 patients, by adding a sleeve gastrectomy with a 40G bougie. This step turned the 20-percent nausea and vomiting incidence rate to virtually zero in the early postoperative period. Interestingly, it was found that, with a follow-up raging from 3 to 8 months, adding the sleeve gastrectomy does not add any weight loss to this leaner group, and carries thus far around 81 percent of T2DM remission. We believe that resecting the stomach longitudinally and removing one of the major ghrelin production sites— T2DM may be an OPERABLE intestinal illness

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Bariatric Times - December 2008 Table of Contents Patient Management Perspective Diabetes Perspective Interview: ASMBS’s Georgeann Mallory Editorial Message Editorial Board Body Contouring Perspective Meeting Perspective Journal Watch Advertiser Index News & Trends

Bariatric Times - December 2008

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