Comparative efficacy and safety of the duodenal-jejunal bypass liner in obese patients with type 2 diabetes mellitus: A case control study.

AIMS: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device mimicking surgical duodenal-jejunal bypass, and is indicated for the treatment of obesity-associated type 2 diabetes mellitus. This analysis was conducted to evaluate the efficacy and safety of the DJBL in comparison to lifestyle changes and antidiabetic drugs. MATERIALS AND METHODS: To determine the efficacy and long-term safety of the DJBL, data concerning 235 obese patients with type 2 diabetes mellitus from the German DJBL registry were analysed. For comparison with standard treatment, propensity-score-matching with patients from the German DPV registry, including the matching parameters sex, age, diabetes duration, baseline BMI and baseline HbA1c, was applied. The final matched cohort consisted of 111 patients in the DJBL group and 222 matched control DPV patients. RESULTS: Mean treatment time with the DJBL was 47.5 ± 12.2 weeks, mean BMI reduction was 5.0 kg/m2 (P < .001) and mean HbA1c reduction was 1.3% (11.9 mmol/mol) (P < .001). Reduction of antidiabetic medications and improvements in other metabolic and cardiovascular risk parameters was observed. In comparison to the matched control group, mean reductions in HbA1c (-1.37% vs -0.51% [12.6 vs 3.2 mmol/mol]; P < .0001) and BMI (-3.02 kg/m2 vs -0.39 kg/m2 ; P < .0001) were significantly higher. Total cholesterol, LDL cholesterol and blood pressure were also significantly better. CONCLUSION: This study provides the largest, so far, hypothesis-generating evidence for a putative positive risk/benefit ratio for treatment of obese patients with type 2 diabetes mellitus with the DJBL as an alternative treatment option for this patient population.

Surgical treatment and outcome of TSH-producing pituitary adenomas.

BACKGROUND: Thyrotropin-producing adenomas (TSHomas) account for approximately 1-2% of all pituitary tumors. Recently, there has been debate on primary treatment as some studies suggest a high rate of hypopituitarism after transsphenoidal surgery and therefore suggest primary use of somatostatin analogs (SSA) instead. We would like to challenge this assumption by presenting our single-center experience with transsphenoidal surgery for TSHoma. METHODS: Fifteen patients treated consecutively between May 2010 and December 2016 were analyzed for long-term postoperative remission and pituitary function. RESULTS: Data on the development of TSH, fT3 and fT4 were available for 12 of 15 patients (mean follow-up was 18 months, 8 patients >12 months), showing mean TSH levels of 1.289 mU/l (0.02-2.04, SD 0.66), mean fT3 levels of 3.76 pmol/l (0.5-6.16, SD 1.8) and mean fT4 levels of 16.5 pmol/l (11.7-21.9, SD 3.66). Six of those patients were substituted with a mean of 85.4 µg L-thyroxine after a median follow-up of 20.7 months. The other six patients did not receive L-thyroxine at a median follow-up of 15.5 months. One patient with a known tumor remnant on MRI stayed euthyreotic with cabergoline at the timepoint of follow-up 22 months after the operation. Control of the corticotrop axis was also available in 12 of 15 with no patient showing a corticotroph insufficiency in the long term. CONCLUSIONS: We argue that transsphenoidal surgery for TSHoma should be considered as the treatment of choice as remission following surgery is highly probable and postoperative hypopituitarism is very unlikely if patients are referred to centers with high pituitary surgery case loads.

Bariatric Surgery Is Protective Against Renal Function Decline in Severely Obese Patients in the Long-Term.

PURPOSE: This study aims to assess the long-term renal effects of bariatric surgery (BS) in severely obese patients over a follow-up period of up to 11 years. MATERIALS AND METHODS: In a retrospective cohort study including 102 patients, patients were stratified by eGFR at baseline and divided into three groups: (1) reduced, (2) normal, and (3) increased filtration rate. Adjustments for age- and sex-related decline in eGFR were performed. We used uni- and multivariate regression analysis to identify variables that were thought to determine change in eGFR. RESULTS: Over a median follow-up of 8.5 years (interquartile range 2.7), eGFR declined from 96.1 ± 20.7 to 84.9 ± 21.0 ml/min (p < 0.001). Among patients with (1), eGFR remained stable (69.1 ± 19.3 ml/min). Among patients with (2), eGFR declined from 99.7 ± 13.3 ml/min to 88.7 ± 19.4 ml/min (p < 0.001). Among patients with (3), eGFR decreased to normal levels (94.2 ± 17.7 ml/min, p < 0.001). Age- and sex-adjusted eGFR increased (6.4 ± 14.4 ml/min; p < 0.05) among patients with reduced filtration rate. Among patients with normal filtration rate, adjusted eGFR remained stable during follow-up (-1.3 ± 15.2 ml/min; n.s.). Among patients with increased filtration rate, adjusted eGFR decreased and remained within the normal range (-13.2 ± 12.2 ml/min; p < 0.001). Change in eGFR showed a negative correlation with eGFR at baseline (B = -0.31; p < 0.001), change in LDL-cholesterol (B = -0.09; p < 0.05), and a negative correlation with treatment requiring hypertension (B = -9.36; p = 0.001). CONCLUSION: BS is protective against renal function decline in severely obese patients in the long term.

Development of Obesity-Associated Comorbidities Post Bariatric Surgery with a Special Focus on Diabetes Remission and Short-Term Relapse.

PURPOSE: The purpose of this study is to study a heterogeneous group of obese patients undergoing Bariatric surgery(BS) and its impact on glycemic control. Secondary endpoints include changes in lipid profile and albuminuria. BS has shown to effectively reduce body-weight. However, the impact on obesity-related comorbidities varies strongly between individuals. Especially postoperative short- and long-term improvement of Diabetes is an active area of investigation. METHODS: We conducted a retrospective analysis from baseline to 24 months post bariatric surgery in our interdisciplinary obesity outpatient-clinic. Follow-up data was collected from 215 patients who had undergone either Roux-en-Y gastric bypass or Sleeve Gastrectomy. The prevalence of and changes in the major obesity-related comorbidities and concurrent medication were assessed. RESULTS: Standard parameters of diabetic control showed a U-shaped curve with initial improvement after six months, but with a gradual worsening after the first year of follow-up. Weight loss resulted in dose reduction of oral antidiabetic medication and insulin in 85% and 100% of patients, respectively. With weight loss, a significant improvement in lipid profile one year after surgery was seen. Subgroup analysis demonstrated gender- and age-dependent differences in overall benefit. CONCLUSIONS: Current data on diabetes remission might be too optimistic and close follow-up should be provided to prevent gradual worsening of glucose metabolism after BS.

Somatotrope Pituitary Function in Professional Soccer Players.

BACKGROUND AND OBJECTIVE: Soccer is associated with repetitive head trauma, which, as it is known from sports like football and boxing, can result in hypopituitarism. Gonadotropins and GH are the most common pituitary hormones to become deficient. GH deficiency is associated with an increased risk of cardiovascular mortality and has negative influence on body mass index, visceral fat mass, insulin resistance and sensitivity, bone mineral density and inflammatory markers. Therefore the aim of this study was to evaluate the somatotrope pituitary function in professional soccer players. RESEARCH DESIGN AND METHODS: This clinical study included 15 male, professional soccer players with at least 10 years of professional training. Basal hormonal parameters of the pituitary axis were obtained from the participants. To assess GH-IGF-I axis, glucagon stimulation tests were used. Rise in growth hormone during glucagon test was analyzed and the prevalence of newly diagnosed hormone deficiencies was evaluated. RESULTS: Mean age of all participants was 31±10 years. None of the 15 soccer players had GH deficiency. Mean rising factor of GH after stimulation with glucagon was 100 in all participants. We did not find signs of ACTH, TSH or LH/FSH deficiency in any player. CONCLUSIONS: In this small collective of soccer players we did not find playing soccer to be a risk factor for the development of GH-deficiency. According to our data screening for somatotrope deficiency is not necessary. Further investigations in larger cohorts are needed.

Trends in BMI, Glycemic Control and Obesity-Associated Comorbidities After Explantation of the Duodenal-Jejunal Bypass Liner (DJBL).

BACKGROUND: A novel-approach for treatment of obesity and diabetes mellitus type 2 (T2DM) is represented by the endoscopic duodenal-jejunal bypass liner (DJBL). Recent data from the German DJBL registry provide evidence for substantial efficacy of the DJBL during the implantation period in obese patients with T2DM. However, little is known about the trends of glycemic control, BMI, and comorbidities after explantation of the DJBL, which have been investigated in the registry in this report. METHODS: Patients were selected from the registry if they had a dataset at implantation, explantation, and at least one time point after explantation of the DJBL (n = 77). We also investigated a subgroup of patients with available data at least 1 year (-2 weeks) after explantation of the DJBL (n = 32). RESULTS: For a mean BMI at implantation and a mean follow-up period, an increase of BMI of 2.1 kg/m2 (CI 0.8-3.2; p = 0.013) had to be expected (for HbA1c 0.3% (CI - 0.0-0.7; p = n.s.), respectively). In the subgroup analysis, HbA1c and BMI increased after explantation of the DJBL but stayed significantly below baseline levels. Meanwhile, the mean number of antidiabetic drugs slightly increased. There was deterioration seen for blood pressure and LDL cholesterol over the postexplantation period to approximately baseline levels (or higher). CONCLUSION: With this data, we show that improvement of HbA1c and BMI can be partly maintained over a time of nearly 1-year postexplantation of the DJBL. However, for HbA1c, this may be biased by intensified medical treatment and effects deteriorated with time after explantation. These results suggest that implantation of the DJBL needs to be integrated in a long-term weight management program as most of other interventions in obese patients with T2DM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02731859.

Longitudinal evaluation of efficacy, safety and nutritional status during one-year treatment with the duodenal-jejunal bypass liner.

BACKGROUND: The endoscopic duodenal-jejunal bypass liner (DJBL) represents a novel temporary endoscopic approach for treatment of obesity-associated type 2 diabetes. Recent results from the German DJBL registry confirmed substantial positive metabolic effects of the DJBL in type 2 diabetes. However, the last Food and Drug Administration trial was stopped due to a high occurrence of hepatic abscesses (3.5%). OBJECTIVES: Here, we analyzed time courses of development of co-morbidities, nutritive changes, and occurrence of adverse events during the 1-year treatment phase with the DJBL in the German DJBL registry. METHODS: Sixty-six patients from the registry were analyzed for efficacy, safety, and nutritional status. Patient data sets were analyzed at implantation, 3 and 6 months after implantation, and at explantation visits. RESULTS: Weight, body mass index, glycated hemoglobin, and low-density lipoprotein cholesterol primarily declined during the first 3 months after implantation, whereas systolic and diastolic blood pressure were predominantly reduced during the second half of the treatment phase. Severe DJBL-associated side effects were mainly documented at the explantation visit (intestinal obstruction [1.7%], dislocation [1.7%], and liver abscess [1.7%]). Measurements of serum concentrations of ferritin, albumin, vitamin B12, folic acid, 25-hydroxyvitamin D3 (25 OH-Vit-D3), and calcium provided suggestive evidence of a possible decrease of nutritional absorption of vitamins and trace elements by the DJBL. CONCLUSIONS: The DJBL demonstrates high efficacy with substantial improvement of all parameters of the metabolic syndrome and the potential for reduction of comedications in overweight patients with type 2 diabetes. These registry results are important to optimize recommendations for adaptation of concomitant medication, surveillance of adverse events, nutritional status and supplementation, and adaptation of the implantation period of the DJBL.