Influence And Mechanism Of Intensive Glycemic Control In Patients With Diabetes During Enteral Nutrition After Gastrectomy

Diabetes mellitus occurs throughout the world, but is more common(especially type 2) in more developed countries. The increase in rates in developing countries follows the trend of urbanization and lifestyle changes, including a "Western-style" diet. The greatest increase in rates was expected to occur in China. Hyperglycemia is associated with an increased morbidity and mortality both in surgical and critically ill patients.The changes that are the result of a transient insulin resistance. Evidence from experimental research and human studies in the last years has suggested that innate immune pathways and inflammatory mechanisms also might play a role. Diabetic patients undergoing major surgery are exposed to metabolic and endocrine alterations in carbohydrate, protein, and insulin metabolism. Previous studies have suggested that intensive glycemic control in the peri-operative period may decrease infections and improve outcome. However, other studies have suggested that side effects from low glucose levels, such as seizures and increased risk of death, have prevented widespread use of this strategy. These conflicting results suggest that the optimal management of postoperative serum glucose levels in patients after surgery remains debatable.In this study, we compared intensive and conventional strategies for glycemic management of hyperglycemia in patients with diabetes during enteral nutrition after gastrectomy. Insulin resistance index was evaluated using homeostasis model assessment(HOMA). The expression of T cell subsets(CD3+,CD4+,CD8+,CD4+/CD8+), natural killer(NK)cell, HLA-DR, immunoglobin, tumor necrosis factor(TNF)-α, interleukin(IL)-1 and IL-6, CRP were detected and compared between the two groups. This study showed that the influence and underlying mechanisms of intensive glycemic control. This research was divided into four parts:Part I: Intensive glycemic control and postoperative outcomes in patients with diabetes during enteral nutrition after gastrectomyMethods 1. Diabetic patients(n=248) who underwent gastrectomy between 2006 and 2014 were collected in the first affiliated hospital of Zhengzhou university. 212 patients were randomized to intensive glycemic(IG) management with continuous insulin infusion(target glucose 4.4-6.1 mmol/l) or conventional glycemic(CG) management with intermittent bolus insulin(target glucose <11.1 mmol/l). 2. Patients were infused with 250 ml of normal saline, starting within 12 h after surgery. Patients received feedings of 20 ml/h SP or TPF(Nutricia) through a naso-jejunal tube beginning on the first postoperative day, with the rate increasing 10 ml/h as tolerated every 12-24 h, to a maximum rate of 80 ml/h. 3. Blood glucose concentrations, insulin administration, volume of enteral and parenteral nutrition and additional intravenous glucose administered were recorded. 4. Postoperative surveillance included clinical examinations and laboratory tests. Outcome measures included postoperative morbidity and mortality rates.Results 1. Blood glucose levels were significantly lower and mean insulin dose was significantly higher in the IG than in the CG group. 2. The rate of severe hypoglycemia was significantly higher in the IG than in the CG group. The percentage of patients experiencing severe hyperglycemia was significantly lower in the IG than in the CG group, and patients in the IG group were significantly more likely to achieve target blood glucose levels. 3. The rate of infection at the surgical site was significantly lower in the IG than in the CG group. The rates of other infective complications, bleeding, delayed gastric emptying, obstruction, hepatic dysfunction, renal dysfunction and circulatory insufficiency were similar in the two groups.Part II: Intensive glycemic control and insulin resistance in patients with diabetes during enteral nutrition after gastrectomyMethods 1. Diabetic patients(n=248) who underwent gastrectomy between 2006 and 2014 were collected in the first affiliated hospital of Zhengzhou university. 212 patients were randomized to intensive glycemic(IG) management with continuous insulin infusion(target glucose 4.4-6.1 mmol/l) or conventional glycemic(CG) management with intermittent bolus insulin(target glucose <11.1 mmol/l). Patients received enteral nutrition beginning on the first postoperative day. The blood samples were collected from the peripheral venous on the morning of preoperative day after overnight fasting and on postoperative days 1, 3, and 7 when nutrition support was ceased at least 5 hours. 2. Blood glucose was detected by automatic biochemistry analyzer in 212 patients with diabetes during enteral nutrition after gasterctomy.3. C-peptide was detected by ARCHITECT C-peptide Reagent Kit in 212 patients with diabetes during enteral nutrition after gasterctomy. 4. Total protein, albumin, prealbumin, triglycerides, cholesterol were detected by automatic biochemistry analyzer.Results 1. Fasting blood glucose levels were similar in the two groups before sugery. Fasting Blood glucose levels were significantly lower in the IG than in the CG group after gasterctomy. 2. Intensive glycemic control downregulaed the C-peptide expression and HOMA2-IR after gasterctomy. 3. Total protein, albumin, prealbumin levels were significantly higher in the IG than in the CG group after gasterctomy. Triglycerides, cholesterol levels were similar in the two groups after gasterctomy.Part III: Intensive glycemic control and immunity in patients with diabetes during enteral nutrition after gastrectomyMethods 1. Diabetic patients(n=248) who underwent gastrectomy between 2006 and 2014 were collected in the first affiliated hospital of Zhengzhou university. 212 patients were randomized to intensive glycemic(IG) management with continuous insulin infusion(target glucose 4.4-6.1 mmol/l) or conventional glycemic(CG) management with intermittent bolus insulin(target glucose<11.1 mmol/l). Patients received enteral nutrition beginning on the first postoperative day. The blood samples were collected from the peripheral venous on the morning of preoperative day after overnight fasting and on postoperative days 1, 3, and 7 when nutrition support was ceased at least 5 hours.2. The expression of T cell subsets(CD3+,CD4+,CD8+,CD4+/CD8+)and natural killer(NK)cell were detected by BD Mutitest 6-colour TBNK Reagent. 3. The expression of HLA-DR was detected by Anti-HLA-DR(L243) and flow cytometry. 4. The expression of Ig G, Ig A and Ig M were detected by automatic biochemistry analyzer.Results 1. CD3+、CD4+、CD4+/CD8+ and NK levels were significantly lower in the two groups compared postoperative and preopreative. CD8+ levels were higher in the two groups compared postoperative and preopreative. CD4+/CD8+ levels were significantly higher in the IG than in the CG group after gasterctomy. 2. HLA-DR levels were significantly lower in the two groups compared postoperative and preoperative. HLA-DR levels were higher in the IG than in the CG group after gasterctomy. 3. Ig G, Ig A and Ig M levels were significantly lower in the two groups compared postoperative and preoperative and similar in the two groups after gasterctomy.Part IV: Intensive glycemic control and inflammation in patients with diabetes during enteral nutrition after gastrectomyMethods 1. Diabetic patients(n=248) who underwent gastrectomy between 2006 and 2014 were collected in the first affiliated hospital of Zhengzhou university. 212 patients were randomized to intensive glycemic(IG) management with continuous insulin infusion(target glucose 4.4-6.1 mmol/l) or conventional glycemic(CG) management with intermittent bolus insulin(target glucose <11.1 mmol/l). Patients received enteral nutrition beginning on the first postoperative day. The blood samples were collected from the peripheral venous on the morning of preoperative day after overnight fasting and on postoperative days 1, 3, and 7 when nutrition support was ceased at least 5 hours. 2. The expression of IL-1 and IL-6 were detected by ELISA Kit in 212 patients with diabetes during enteral nutrition after gasterctomy. 3. The expression of CRP was detected by automatic specific protein instrument. 4. The expression of TNF-α was detected by TNF-α ELISA Kit in 212 patients with diabetes during enteral nutrition after gasterctomy.Results 1. IL-1 levels were similar in the two groups after gasterctomy. IL-6 levels were significantly lower in the IG than in the CG group after gasterctomy. Both IL-1 and IL-6 levels were significantly higher in the two groups compared postoperative and preoperative. 2. CRP levels were significantly higher in the two groups compared postoperative and preoperative.CRP levels were significantly lower in the IG than in the CG group after gasterctomy. 3. TNF-α levels were significantly higher in the two groups compared postoperative and preoperative. TNF-α levels were lower in the IG than in the CG group on postoperative day 3.Conclusions 1. Intensive glycemic control was associated with higher hypoglycemia and more likely to achieve target blood glucose levels. The rate of infection at the surgical site was significantly lower in the IG than in the CG group. 2. Intensive glycemic control downregulated the C-peptide expression and was associated with improvement of insunlin resistance after gastrectomy. 3. Intensive glycemic control was associated with improvement of immunological suppression after gastrectomy. 4. Intensive glycemic control was associated with reduce of inflammation after gastrectomy.