Oncometabolic surgery in patients with gastric cancer and type 2 diabetes
T2D is caused by an increase in insulin resistance. The insulin secretory function compensates for the increase in insulin resistance. However, if this compensation is not enough, the glucose level spirals out of control. If this hyperglycemic stress persists for a long time, the function of pancreatic β cells is eventually destroyed, leading to a decrease in insulin secretion. Because Asians have fewer pancreatic β cells, insulin secretion decreases more severely than in Westerners.
The mechanism of gastric cancer surgery as metabolic surgery has some similarities to that of bariatric RYGP. Reduction of residual stomach volume by gastric resection results in caloric restriction and weight loss. In the case of Billroth II (BII) or Roux-en-Y gastrectomy, food material bypasses the duodenum and proximal jejunum due to bypass of the digestive tract and reaches the distal ileum sooner than it does in normal individuals. The difference is that gastric cancer patients are relatively less obese; therefore, the effect of weight loss is small compared to that of bariatric patients. In the case of a subtotal gastrectomy, the fundus cannot be excised, which is disadvantageous in reducing caloric restriction and ghrelin secretion. The bypass length is shorter than that of bariatric surgery, therefore, the effect of enteric hormonal changes may be weaker than that of bariatric RYGP.
T2D remission rate after conventional subtotal gastrectomy was 11.2-22.2%, and after Roux-en-Y reconstruction it was 20-30.7%15,27,34,35,36. After LRYG, the remission rate would be 11.6 to 78.6%24.25. In this study, the postoperative remission rate was approximately 47%, and when partial remission was included in this rate, it was approximately 55.6% 1 year after surgery. This remission rate is comparable to the remission rate of T2DM in class II obese patients4,5,37. One of the reasons DM improves after bariatric RYGP is weight loss, which has the effect of improving insulin resistance. Another reason is the effect of hormonal changes at the insuloenteric axis, caused by the change in the passage of the digestive tract, which contributes more than weight loss. The foregut hypothesis posits that patients undergoing duodenal bypass experience antidiabetic effects due to a decrease in anti-incretin factor. The hindgut hypothesis posits that early food contact with the distal ileum ameliorates diabetes through increased and early release of hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY)17,18,19,20,21.
The improvement in T2D after conventional gastrectomy is thought to be due to an improvement in insulin resistance due to weight loss. However, in several previous bariatric studies or gastrectomy studies, pancreatic β-cell function has been reported to play a greater role in T2DM remission.38,39,40. In our study, the preoperative insulinogenic index, which represents the function of insulin secretion, was the only significant factor influencing the remission of T2DM. Insulin resistance showed rapid improvement with no weight loss within a week of surgery, after which it worsened. Insulin resistance and weight loss showed no difference 1 year after surgery between the two groups. In contrast, insulin secretion showed a significant difference between the two groups 1 year after surgery. In addition, the shape of the OGTT graph of the non-remission group showed a normal shape, but the glucose value was abnormal. These results indicated that the improvement in T2D after LRYG caused by increased insulin secretion due to the effect of metabolic surgery was greater than the improvement caused by weight reduction, which is similar to the results of studies conducted in obese patients with T2DM.21.
A statistically significant factor related to T2D remission was the preoperative insulinogenic index. The preoperative insulinogenic index was a useful index (AUC = 0.694) and the insulinogenic index cutoff value was 0.105 (sensitivity = 0.609, specificity = 0.773). (Fig. 4) The normal value of the insulinogenic index is known to be 0.4 or more; however, LRYG may be considered in patients with an insulinogenic index of 0.1 or greater.
The OGTT test is a very uncomfortable examination because it causes dizziness, nausea, vomiting, etc. It requires several blood samples during the same visit, so patient compliance is poor. In this study, various indices of diabetes were obtained by testing OGTT and serum insulin levels. It is interesting to determine which factor is the most important in the indication of T2D remission by calculating the indices. The mixed meal tolerance test does not allow the calculation of various MS indices. Although the OGTT is an impractical test, it was used in this study. All patients received informed consent for oncometabolic surgery and OGTT testing. This study began in 2010. At the time, it was thought that a biliopancreatic limb and a food limb of about 80 cm would be sufficient25. Nowadays, longer limbs are accepted as the usual method41. If performed with a longer biliopancreatic limb and alimentary limb, better results can be expected.
As this study is a retrospective study, the influence of a selection bias cannot be excluded. Some patients missed follow-up visits and there were difficulties performing the OGTT test, so some lab results were missed. Of the 58 patients, 10 had missing data and 48 patients were included in the analyses. This study only had 1-year follow-up results and a small number of patients, which limited statistical power. There is a lack of comparative assessment of the nutritional status of patients.
The effects of LRYG on weight loss and improvement in insulin resistance were not different between the two groups, and the difference in insulin secretory function was the most important factor associated with remission of T2DM. The results of this study show that the effect of LRYG in T2DM patients with low BMI was similar to that of metabolic surgery in obese T2DM patients. Oncometabolic surgery may be one of the elective surgeries for T2DM gastric cancer patients with a strong possibility of long-term survival and well-preserved pancreatic β-cell function even if they are of normal weight. Moreover, these results suggest the possibility of extending the indication of metabolic surgery for T2DM patients who are overweight or have a normal BMI.