Gastric bypass leads to improvement of diabetic neuropathy independent of glucose normalization--results of a prospective cohort study (DiaSurg 1 study).

OBJECTIVE: Surprisingly, 40% to 95% of patients with type 2 diabetes mellitus (T2DM) show early remission of hyperglycemia after obesity surgery. It is unknown to what extent other diabetes-associated comorbidities such as distal peripheral neuropathy (DPN) might be influenced by obesity surgery. This pilot study aimed at providing further evidence for the impact of Roux-en-Y gastric bypass (RYGB) on both glycemic control and DPN in non-severely obese patients with insulin-dependent T2DM. METHODS: In the present prospective cohort study, 20 patients with long-standing, insulin-dependent T2DM and a body mass index (BMI) between 25 and 35 kg/m underwent laparoscopic RYGB. Body mass index, glycosylated hemoglobin (HbA1c), and DPN [quantified by the Neuropathy Symptom Score (NSS) and the Neuropathy Deficit Score (NDS)] were investigated. RESULTS: Six months after surgery, the preoperative BMI of 32.8 ± 2.1 kg/m (mean ± standard deviation) dropped to 25.6 ± 2.5 kg/m (P < 0.001). Preoperative HbA1c levels decreased from 8.5 ± 1.2% to 7.1 ± 1.2% (P < 0.001), with 15% of patients having a normalized HbA1c level lower than 6.2%. Of 12 patients with documented DPN, the median NSS was 8 (range, 0-10) preoperatively and 0 (range, 0-9) postoperatively (P = 0.004), with 8 patients scoring an NSS of 0. The median NDS was 6 (range, 2-8) preoperatively and 4 (range, 0-8) postoperatively (P = 0.027), with 1 patient scoring an NDS of 0. All patients had an improvement or normalization in either 1 or both scores. CONCLUSIONS: As expected, BMI and HbA1c levels improved significantly after RYGB. More interestingly, neuropathy scores, such as NSS and NDS, improved significantly early after surgery. Symptomatic neuropathy was completely reversible in 67% of the patients. These findings add further evidence to the fact that RYGB might be a valuable treatment option not only for improving glycemic control but also for reducing diabetes-associated comorbidities, such as DPN. This points to a complex metabolic effect of RYGB that exceeds glucose normalization. However, the results still need to be confirmed in controlled trials.

Risk of Malnutrition, Trace Metal, and Vitamin Deficiency Post Roux-en-Y Gastric Bypass--a Prospective Study of 20 Patients with BMI < 35 kg/m².

BACKGROUND: Due to its reliable effects on type 2 diabetes mellitus (T2DM) remission, Roux-en-Y gastric bypass (RYGB) has recently been investigated as a treatment option for nonseverely obese patients with T2DM (body mass index (BMI) <35 kg/m(2)). The purpose of this study was to investigate whether RGYB induces malnutrition of macro- and micronutrients within 24 months in these patients. METHODS: A prospective cohort of 20 patients with longstanding, insulin-dependent T2DM and a BMI of 25-35 kg/m(2) were treated with RYGB. The patients were supplemented with over-the-counter, multivitamin, and micronutrient supplements. Serum concentrations of albumin, vitamins, and trace elements, hemoglobin, and bone density were measured preoperatively and over a 24-month period (DRKS00004605). RESULTS: RYGB did not result in underweight or protein malnutrition. No new onset of deficiencies of water- or fat-soluble vitamins developed over the study period. However, serum selenium, zinc, and ferritin decreased significantly (selenium, 1.17 ± 0.13 to 0.89 ± 0.11 µmol/l, p = 0.018; zinc, 13.9 ± 0.5 to 10.8 ± 0.5 µmol/l, p = 0.012; ferritin, 171.7 ± 26.9 to 31.8 ± 11.2 µg/l, p = 0.018). Hemoglobin remained stable. Vitamin D (13.7 ± 1.8 to 19.1 ± 1.1 ng/ml, p = 0.017) and osteocalcin (15.3 ± 1.7 to 25.4 ± 2.7 ng/ml, p = 0.025) rose significantly, whereas the parathyroid hormone remained stable. Despite increased bone formation, bone density decreased (T score hip, 0.15 ± 0.25 to -0.71 ± 0.34, p = 0.005) resulting in a significant increase in osteopenia rates (18 to 50 %, p = 0.046). CONCLUSIONS: This is the first prospective cohort to investigate malnutrition after RYGB in nonseverely obese patients. These patients are at risk of developing iron, selenium, and zinc deficiencies within 24 months, as well as osteopenia despite an increase in bone formation.

DiaSurg 2 trial--surgical vs. medical treatment of insulin-dependent type 2 diabetes mellitus in patients with a body mass index between 26 and 35 kg/m2: study protocol of a randomized controlled multicenter trial--DRKS00004550.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a disease with high prevalence, associated with severe co-morbidities as well as being a huge burden on public health. It is known that glycemic control decreases long-term morbidity and mortality. The current standard therapy for T2DM is medical treatment. Several randomized controlled trials (RCTs) performed in obese patients showed remission of T2DM after bariatric surgery. Recent RCTs have shown bariatric procedures to produce a similar effect in non-morbidly and non-severely obese, insulin-dependent T2DM patients suggesting procedures currently used in bariatric surgery as new therapeutical approach in patients with T2DM. This study aims at investigating whether Roux-en-Y gastric bypass (RYGB) is an efficient treatment for non-severely obese T2DM patients in terms of preventing long-term complications and mortality. METHODS: The DiaSurg 2 trial is a multicenter, open randomized controlled trial comparing RYGB including standardized medical treatment if needed to exclusive standardized medical treatment of T2DM (control group). The primary endpoint is a composite time-to-event endpoint (cardiovascular death, myocardial infarction, coronary bypass, percutaneous coronary intervention, non-fatal stroke, amputation, surgery for peripheral atherosclerotic artery disease), with a follow-up period of 8 years. Insulin-dependent T2DM patients aged between 30 and 65 years will be included and randomly assigned to one of the two groups. The experimental group will receive RYGB and, if needed, standardized medical care, whereas the control group will receive exclusive standardized medical care, both according to the national treatment guidelines for T2DM. Statistical analysis is based on Cox proportional hazards regression for the intention-to-treat population. Assuming a loss to follow-up rate of 20%, 200 patients will be randomly allocated to the comparison groups. A total sample size of n=400 is sufficient to ensure 80% power in a two-tailed significance test at alpha=5%. DISCUSSION: The DiaSurg2 trial will yield long-term data (8 years) on diabetes-associated morbidity and mortality in patients with insulin-dependent T2DM receiving either RYGB or standardized medical care. TRIAL REGISTRATION: The trial protocol has been registered in the German Clinical Trials Register DRKS00004550.

Challenges and pitfalls of experimental bariatric procedures in rats.

INTRODUCTION: The impact of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on obesity and obesity-related diseases is unquestionable. Up to now, the technical descriptions of these techniques in animals/rats have not been very comprehensive. METHODS: For SG and RYGB, operating time, learning curve, and intraoperative mortality in relation to weight of the rat and type of anesthesia were recorded. Furthermore, a review of the literature on experimental approaches towards SG and RYGB in rats was carried out, merging in a detailed technical description for both procedures. RESULTS: The data presented here revealed that the mean operating time for SG (69.4 ± 22.2 min (SD)) was shorter than for RYGB (123.0 ± 20.7 min). There is a learning curve for both procedures, resulting in a reduced operating time of up to 60% in SG and 35% in RYGB (p < 0.05; t-test). However, with increased weight, operating time increases to about 80 min for SG and about 120 min for RYGB. Obese rats have an increased intraoperative mortality rate of up to 50%. After gaseous anesthesia the mortality can be even higher. The literature search revealed 40 papers dealing with SG and RYGB in rats. 18 articles (45%) contained neither photographs nor illustrations; 14 articles (35%) did not mention the applied type of anesthesia. The mortality rate was described in 15 papers (37.5%). CONCLUSION: Experimental obesity surgery in rats is challenging. Because of the high mortality in obese rats operated under gaseous anesthesia, exercises to establish the techniques should be performed in small rats using intraperitoneal anesthesia.