Weight loss and treatment patterns in a real-world population of adults receiving liraglutide 3.0 mg for weight management in routine clinical practice in Switzerland (ADDRESS study).

AIM: To assess weight loss associated with liraglutide 3.0 mg treatment in individuals with obesity (body mass index [BMI] ≥30 kg/m2 ) or overweight (BMI > 27 to <30 kg/m2 ) in a reimbursed, real-world setting in Switzerland. MATERIALS AND METHODS: ADDRESS was a non-comparative, multicentre, retrospective exposure cohort study in Switzerland, examining weight loss in individuals with obesity or overweight whose treatment was reimbursed (divided into BMI subgroups) or non-reimbursed. The primary outcomes were proportions of participants in the reimbursed cohort achieving predefined weight loss targets with liraglutide 3.0 mg at Week 16 (≥5% and ≥7% for the lower BMI [28 to <35 kg/m2 with weight-related comorbidities] and higher BMI [≥35 kg/m2 ] subgroups, respectively) and Month 10 (additional ≥5% from Week 16; per Swiss reimbursement criteria). RESULTS: The full analysis set comprised 258 individuals (195 reimbursed; 63 non-reimbursed). In the reimbursed cohort, 139 individuals (71.3%) achieved their weight loss targets at Week 16. Of individuals who met the Week-16 criteria, 43.2% attained an additional 5% weight loss at Month 10. In 162 individuals for whom data were recorded at Month 10, the mean (standard deviation) relative weight loss from baseline to Month 10 was -12.4% (6.4%). CONCLUSIONS: Although reimbursement criteria may be difficult to achieve, particularly the additional weight loss of 5% from Week 16 to Month 10, a clinically relevant overall weight loss from baseline to Month 10 was shown in most individuals with obesity or overweight who received liraglutide 3.0 mg.

The 'Behavioral Balance Model': A new perspective on the aetiology and therapy of obesity.

Obesity is a debilitating disease of global proportions that necessitates refined, concept-driven therapeutic approaches. Policy makers, the public and even health care professionals, but also individuals with obesity harbour many misconceptions regarding this disease, which leads to prejudice, negative attitudes, stigmatization, discrimination, self-blame, and failure to provide and finance adequate medical care. Decades of intensive, successful scientific research on obesity have only had a very limited effect on this predicament. We propose a science-based, easy-to-understand conceptual model that synthesizes the complex pathogenesis of obesity including biological, psychological, social, economic and environmental aspects with the aim to explain and communicate better the nature of obesity and currently available therapeutic modalities. According to our integrative 'Behavioral Balance Model', 'top-down cognitive control' strategies are implemented (often with limited success) to counterbalance the increased 'bottom-up drive' to gain weight, which is triggered by biological, psycho-social and environmental mechanisms in people with obesity. Besides offering a deeper understanding of obesity, the model also highlights why there is a strong need for multimodal therapeutic approaches that may not only increase top-down control but also reduce a pathologically increased bottom-up drive.

Sleep deprivation prevents counterregulatory adaptation to recurrent hypoglycaemia.

AIMS/HYPOTHESIS: Attenuated counterregulation after recurrent hypoglycaemia is a major complication of diabetes treatment. As there is previous evidence for the relevance of sleep in metabolic control, we assessed the acute contribution of sleep to the counterregulatory adaptation to recurrent hypoglycaemia. METHODS: Within a balanced crossover design, 15 healthy, normal-weight male participants aged 18-35 years underwent three hyperinsulinaemic-hypoglycaemic clamps with a glucose nadir of 2.5 mmol/l, under two experimental conditions, sleep and sleep deprivation. Participants were exposed to two hypoglycaemic episodes, followed by a third hypoglycaemic clamp after one night of regular 8 h sleep vs sleep deprivation. The counterregulatory response of relevant hormones (glucagon, growth hormone [GH], ACTH, cortisol, adrenaline [epinephrine] and noradrenaline [norepinephrine]) was measured, and autonomic and neuroglycopenic symptoms were assessed. RESULTS: Sleep deprivation compared with sleep dampened the adaptation to recurrent hypoglycaemia for adrenaline (p=0.004), and this pattern also emerged in an overall analysis including adrenaline, GH and glucagon (p=0.064). After regular sleep, the counterregulatory responses of adrenaline (p=0.005), GH (p=0.029) and glucagon (p=0.009) were attenuated during the 3rd clamp compared with the 1st clamp, but were preserved after sleep deprivation (all p>0.225). Neuroglycopenic and autonomic symptoms during the 3rd clamp compared with the 1st clamp were likewise reduced after sleep (p=0.005 and p=0.019, respectively). In sleep deprivation, neuroglycopenic symptoms increased (p=0.014) and autonomic symptoms were unchanged (p=0.859). CONCLUSIONS/INTERPRETATION: The counterregulatory adaptation to recurrent hypoglycaemia is compromised by sleep deprivation between hypoglycaemic episodes, indicating that sleep is essential for the formation of a neurometabolic memory, and may be a potential target of interventions to treat hypoglycaemia unawareness syndrome.

Take Control: A randomized trial evaluating the efficacy and safety of self- versus physician-managed titration of insulin glargine 300 U/mL in patients with uncontrolled type 2 diabetes.

AIM: To compare the efficacy and safety of self- versus physician-managed titration of insulin glargine 300 U/mL (Gla-300) in people with inadequately controlled type 2 diabetes. METHODS: Take Control (EudraCT number: 2015-001626-42) was a 24-week, multi-national, open-label, controlled, two-arm, parallel-group study in insulin-naïve and pre-treated participants, randomized 1:1 to a self- or physician-managed titration of Gla-300. The fasting self-monitored plasma glucose (SMPG) target was 4.4 to 7.2 mmol/L. The primary outcome was non-inferiority of glycated haemoglobin (HbA1c) change from baseline to week 24. Secondary outcomes included SMPG target achievement without hypoglycaemia, hypoglycaemia incidence, adverse events and participant-reported outcomes (PROs). RESULTS: At week 24, the least squares (LS) mean HbA1c reduction was 0.97% (10.6 mmol/mol) and 0.84% (9.2 mmol/mol) in the self- and physician-managed groups, respectively, with an LS mean difference of -0.13% [95% confidence interval -0.2619 to -0.0004] (-1.4 mmol/mol [-2.863 to -0.004]), demonstrating non-inferiority (P < 0.0001) and superiority (P = 0.0247) of self- versus physician-managed titration. Significantly more of the self- than physician-managed group achieved SMPG target without hypoglycaemia (67% vs 58%; P = 0.0187). Overall, hypoglycaemia incidence was similar in each group. No safety concerns were reported. In both groups, similar PRO improvements were observed for distress related to diabetes disease burden and for confidence in diabetes self-management, with even more individuals achieving a clinically relevant reduction in emotional burden and fewer individuals with high emotional burden in the self-managed group. CONCLUSIONS: Self-managed titration of Gla-300 was superior to physician-managed titration in terms of HbA1c reduction, accompanied by similar total PRO scores, with a clinically relevant reduction in emotional burden, and similar hypoglycaemia frequency.

Spiroergometric assessment of cardiorespiratory fitness in subjects with severe obesity: A challenge of reference.

BACKGROUND AND AIMS: Severe obesity is associated with poor physical performance but objective data are scarce. METHODS AND RESULTS: Bicycle spiroergometry data with focus on peak oxygen uptake (V˙O2,peak) and workload (Wpeak) from 476 subjects with severe obesity (BMI ≥ 35.0 kg/m2; 70% women) were analysed. In a first step, V˙O2,peak values were compared with reference values calculated upon different formulas (Wassermann; Riddle). Thereafter, multivariate regression analyses were performed to identify determinants of cardiorespiratory fitness. Cardiorespiratory fitness reference classes for V˙O2,peak and Wpeak were established by stratifying the sample upon identified determinants. Absolute V˙O2,peak (1.87 ± 0.47 vs. 2.40 ± 0.59 l/min) and Wpeak (131 ± 26 vs. 168 ± 44 W) were lower in women than men (both p<0.001). Same pattern was found for relative V˙O2,peak and Wpeak, respectively (both p < 0.05). In women, measured V˙O2,peak was lower than predicted by Wasserman (p < 0.001) but not by Riddle (p = 0.961). In men, V˙O2,peak was lower than calculated by both Wasserman and Riddle formulas (both p ≤ 0.003). Multivariate analyses revealed height and age to be the main determinants of cardiorespiratory fitness in both sexes. Subsequent statistical analyses of calculated reference fitness classes revealed that V˙O2,peak and Wpeak differed between the age- and height-defined groups in both sexes (all p < 0.001). CONCLUSION: Data indicate that the evaluation of cardiorespiratory fitness in subjects with severe obesity is largely biased by selected references values for comparison. Our newly established reference fitness classes upon height and age might be helpful in the clinical context when dealing with obese patients.

Use and effectiveness of a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) in a real-world population with type 2 diabetes: Results from a European, multicentre, retrospective chart review study.

AIMS: To describe the real-world use and effectiveness of IDegLira, a fixed-ratio combination of the basal insulin degludec, and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide. MATERIALS AND METHODS: This European, multicentre, retrospective chart review comprised adults (n = 611) with type 2 diabetes, who started IDegLira ≥6 months before data collection. Clinical characteristics were assessed at baseline (defined as the most recent recording during the 6 months before the first IDegLira prescription) and 3, 6, 9 and 12 months (± 45 days for each time point) after commencing IDegLira, where data were available. RESULTS: Baseline regimens included non-injectable medications (19%), basal insulin (19%), GLP-1RA (10%), free combination therapy (insulin/GLP-1RA, 24%) and multiple daily-dose insulin injections (MDI, 28%), all ± oral antidiabetic drugs. After 6 months, significant glycated haemoglobin (HbA1c) reductions were observed in patients overall and in all subgroups (-10 mmol/mol [-0.9%] overall; P < .0001), and a significant reduction in mean body weight (-0.7 kg; P < .05) was observed in patients overall and in patients receiving MDI (-2.4 kg; P < .0001). The mean IDegLira dose was 22, 30 and 32 dose steps at initiation, and at 6 and 12 months follow-up, respectively. In total, only 67 patients reached the maximum 50 dose steps, with most coming from the free combination therapy (n = 31) or MDI (n = 15) baseline regimen groups. Hypoglycaemia rates were reduced by 82% (rate ratio 0.18; P < .0001) in the 6-month period after vs before IDegLira initiation. Overall, a total of 12 patients experienced 15 events in the 6 months after IDegLira initiation. CONCLUSION: In real-world practice, after 6 months and at a moderate dose, IDegLira resulted in substantial reductions in HbA1c and body weight, with a reduced risk of hypoglycaemia.

A European, multicentre, retrospective, non-interventional study (EU-TREAT) of the effectiveness of insulin degludec after switching basal insulin in a population with type 1 or type 2 diabetes.

AIMS: To evaluate the clinical effectiveness of switching to insulin degludec (IDeg) in insulin-treated patients with either type 1 diabetes (T1DM) or type 2 diabetes (T2DM) under conditions of routine clinical care. MATERIALS AND METHODS: This was a multicentre, retrospective, chart review study. In all patients, basal insulin was switched to IDeg at least 6 months before the start of data collection. Baseline was defined as the most recent recording during the 3-month period before first prescription of IDeg. Values are presented as mean [95%CI]. RESULTS: T1DM (n = 1717): HbA1c decreased by -2.2 [-2.6; -2.0] mmol/mol (-0.20 [-0.24; -0.17]%) at 6 months vs baseline (P < .001). Rate ratio of overall (0.79 [0.69; 0.89]), non-severe nocturnal (0.54 [0.42; 0.69]) and severe (0.15 [0.09; 0.24]) hypoglycaemia was significantly lower in the 6-month post-switch period vs the pre-switch period (P < .001 for all). Total daily insulin dose decreased by -4.88 [-5.52; -4.24] U (-11%) at 6 months vs baseline (P < .001). T2DM (n = 833): HbA1c decreased by -5.6 [-6.3; -4.7] mmol/mol (-0.51 [-0.58; -0.43] %) at 6 months vs baseline (P < .001). Rate ratio of overall (0.39 [0.27; 0.58], P < .001), non-severe nocturnal (0.10 [0.06; 0.16], P < .001) and severe (0.075 [0.01; 0.43], P = .004) hypoglycaemia was significantly lower in the 6-month post-switch period vs the pre-switch period. Total daily insulin dose decreased by -2.48 [-4.24; -0.71] U (-3%) at 6 months vs baseline (P = .006). Clinical outcomes for T1DM and T2DM at 12 months were consistent with results at 6 months. CONCLUSIONS: This study demonstrates that switching patients to IDeg from other basal insulins improves glycaemic control and significantly reduces the risk of hypoglycaemia in routine clinical practice.

Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial.

Importance: Sleeve gastrectomy is increasingly used in the treatment of morbid obesity, but its long-term outcome vs the standard Roux-en-Y gastric bypass procedure is unknown. Objective: To determine whether there are differences between sleeve gastrectomy and Roux-en-Y gastric bypass in terms of weight loss, changes in comorbidities, increase in quality of life, and adverse events. Design, Setting, and Participants: The Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), a 2-group randomized trial, was conducted from January 2007 until November 2011 (last follow-up in March 2017). Of 3971 morbidly obese patients evaluated for bariatric surgery at 4 Swiss bariatric centers, 217 patients were enrolled and randomly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass with a 5-year follow-up period. Interventions: Patients were randomly assigned to undergo laparoscopic sleeve gastrectomy (n = 107) or laparoscopic Roux-en-Y gastric bypass (n = 110). Main Outcomes and Measures: The primary end point was weight loss, expressed as percentage excess body mass index (BMI) loss. Exploratory end points were changes in comorbidities and adverse events. Results: Among the 217 patients (mean age, 45.5 years; 72% women; mean BMI, 43.9) 205 (94.5%) completed the trial. Excess BMI loss was not significantly different at 5 years: for sleeve gastrectomy, 61.1%, vs Roux-en-Y gastric bypass, 68.3% (absolute difference, -7.18%; 95% CI, -14.30% to -0.06%; P = .22 after adjustment for multiple comparisons). Gastric reflux remission was observed more frequently after Roux-en-Y gastric bypass (60.4%) than after sleeve gastrectomy (25.0%). Gastric reflux worsened (more symptoms or increase in therapy) more often after sleeve gastrectomy (31.8%) than after Roux-en-Y gastric bypass (6.3%). The number of patients with reoperations or interventions was 16/101 (15.8%) after sleeve gastrectomy and 23/104 (22.1%) after Roux-en-Y gastric bypass. Conclusions and Relevance: Among patients with morbid obesity, there was no significant difference in excess BMI loss between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass at 5 years of follow-up after surgery. Trial Registration: clinicaltrials.gov Identifier: NCT00356213.

Laparoscopic Sleeve Gastrectomy Versus Roux-Y-Gastric Bypass for Morbid Obesity-3-Year Outcomes of the Prospective Randomized Swiss Multicenter Bypass Or Sleeve Study (SM-BOSS).

OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) is performed almost as often in Europe as laparoscopic Roux-Y-Gastric Bypass (LRYGB). We present the 3-year interim results of the 5-year prospective, randomized trial comparing the 2 procedures (Swiss Multicentre Bypass Or Sleeve Study; SM-BOSS). METHODS: Initially, 217 patients (LSG, n = 107; LRYGB, n = 110) were randomized to receive either LSG or LRYGB at 4 bariatric centers in Switzerland. Mean body mass index of all patients was 44 ±â€Š11 kg/m, mean age was 43 ±â€Š5.3 years, and 72% of patients were female. Minimal follow-up was 3 years with a rate of 97%. Both groups were compared for weight loss, comorbidities, quality of life, and complications. RESULTS: Excessive body mass index loss was similar between LSG and LRYGB at each time point (1 year: 72.3 ±â€Š21.9% vs. 76.6 ±â€Š20.9%, P = 0.139; 2 years: 74.7 ±â€Š29.8% vs. 77.7 ±â€Š30%, P = 0.513; 3 years: 70.9 ±â€Š23.8% vs. 73.8 ±â€Š23.3%, P = 0.316). At this interim 3-year time point, comorbidities were significantly reduced and comparable after both procedures except for gastro-esophageal reflux disease and dyslipidemia, which were more successfully treated by LRYGB. Quality of life increased significantly in both groups after 1, 2, and 3 years postsurgery. There was no statistically significant difference in number of complications treated by reoperation (LSG, n = 9; LRYGB, n = 16, P = 0.15) or number of complications treated conservatively. CONCLUSIONS: In this trial, LSG and LRYGB are equally efficient regarding weight loss, quality of life, and complications up to 3 years postsurgery. Improvement of comorbidities is similar except for gastro-esophageal reflux disease and dyslipidemia that appear to be more successfully treated by LRYGB.

Effect of morbid obesity, gastric banding and gastric bypass on esophageal symptoms, mucosa and function.

BACKGROUND: Obesity and gastroesophageal reflux disease (GERD) are commonly associated diseases. Bariatric surgery has been shown to have various impacts on esophageal function and GERD. Our aim was to evaluate changes in symptoms, endoscopic findings, bolus passage and esophageal function in patients after primary gastric bypass surgery as compared to patients converted from gastric banding to gastric bypass. METHODS: Obese patients scheduled for laparoscopic Roux-en-Y gastric bypass (naïve-to-bypass) and patients who previously underwent gastric banding and were considered for conversion from gastric banding to gastric bypass (band-to-bypass) were included. Patients rated esophageal and epigastric symptoms (100 point VAS) and underwent upper endoscopy, impedance-manometry, and modified "timed barium swallow" before/after surgery. RESULTS: Data from 66 naïve-to-bypass patients (51/66, 77 % females, mean age 41.2 ± 11.1 years) and 68 band-to-bypass patients (53/68, 78 % females, mean age 43.8 ± 10.0 years) were available for analysis. Esophageal symptoms, esophagitis, esophageal motility abnormalities and impaired esophageal bolus transit were more common in patients that underwent gastric banding compared to those that underwent gastric bypass. The majority of symptoms, lesions and abnormalities induced by gastric banding were decreased by conversion to gastric bypass. Esophagitis was present in 28/68 (41 %) and 13/47 (28 %) patients in the band-to-bypass group, pre- versus postoperatively, respectively, (p < 0.05). The percentage of swallows with normal bolus transit increased following transformation from gastric band to gastric bypass (57.9 ± 4.1 and 83.6 ± 3.4 %, respectively, p < 0.01). CONCLUSIONS: From an esophageal perspective, gastric bypass surgery induces less motility disorders and esophageal symptoms and should be therefore favored over gastric banding in difficult to treat obese patients at risk of repeated bariatric surgery.

A genetic variant in proximity to the gene LYPLAL1 is associated with lower hunger feelings and increased weight loss following Roux-en-Y gastric bypass surgery.

OBJECTIVE: Bariatric surgery is the most efficient treatment of severe obesity. We investigated to what extent BMI- or waist-hip ratio (WHR)-related genetic variants are associated with excess BMI loss (EBMIL) two years after Roux-en-Y gastric bypass (RYGB) surgery, and elucidated the affected biological pathways. METHODS: Two-hundred fifty-one obese patients (age: 43 ± 10.7, preoperative BMI: 45.1 ± 6.1 kg/m(2), 186 women) underwent RYGB surgery and were followed up after two years with regard to BMI. Patients were genotyped for 32 single-nucleotide polymorphisms (SNPs) that were investigated with regard to their impact on response to RYGB and preoperatively measured Three Factor Eating Questionnaire (TFEQ) scores. RESULTS: Homozygous T carriers of the SNP rs4846567 in proximity to the Lysophospholipase-like 1 (LYPLAL1) gene showed a 7% higher EBMIL compared to wild-type and heterozygous carriers (p = 0.031). TT-allele carriers showed furthermore lower scores for Hunger (74%, p < 0.001), lower Disinhibition (53%, p < 0.001), and higher Cognitive restraint (21%, p = 0.017) than GG/GT carriers in the TFEQ. Patients within the lowest quartile of Hunger scores had a 32% greater EBMIL compared to patients in the highest quartile (p < 0.001). CONCLUSION: The LYPLAL1 genotype is associated with differences in eating behavior and loss of extensive body weight following RYGB surgery. Genotyping and the use of eating behavior-related questionnaires may help to estimate the RYGB-associated therapy success.

Glycemic increase induced by intravenous glucose infusion fails to affect hunger, appetite, or satiety following breakfast in healthy men.

Meal-dependent fluctuations of blood glucose and corresponding endocrine signals such as insulin are thought to provide important regulatory input for central nervous processing of hunger and satiety. Since food intake also triggers the release of numerous gastrointestinal signals, the specific contribution of changes in blood glucose to appetite regulation in humans has remained unclear. Here we tested the hypothesis that inducing glycemic fluctuations by intravenous glucose infusion is associated with concurrent changes in hunger, appetite, and satiety. In a single blind, counter-balanced crossover study 15 healthy young men participated in two experimental conditions on two separate days. 500 ml of a solution containing 50 g glucose or 0.9% saline, respectively, was intravenously infused over a 1-h period followed by a 1-h observation period. One hour before start of the respective infusion subjects had a light breakfast (284 kcal). Blood glucose and serum insulin concentrations as well as self-rated feelings of hunger, appetite, satiety, and fullness were assessed during the entire experiment. Glucose as compared to saline infusion markedly increased glucose and insulin concentrations (peak glucose level: 9.7 ± 0.8 vs. 5.3 ± 0.3 mmol/l; t(14) = -5.159, p < 0.001; peak insulin level: 370.4 ± 66.5 vs. 109.6 ± 21.5 pmol/l; t(14) = 4.563, p < 0.001) followed by a sharp decline in glycaemia to a nadir of 3.0 ± 0.2 mmol/l (vs. 3.9 ± 0.1 mmol/l at the corresponding time in the control condition; t(14) = -3.972, p = 0.001) after stopping the infusion. Despite this wide glycemic fluctuation in the glucose infusion condition subjective feelings of hunger, appetite satiety, and fullness did not differ from the control condition throughout the experiment. These findings clearly speak against the notion that fluctuations in glycemia and also insulinemia represent major signals in the short-term regulation of hunger and satiety.

Eating behaviour in treatment-seeking obese subjects - Influence of sex and BMI classes.

Obese subjects frequently show an adversely altered eating behaviour. However, little is known on differences in eating behaviour across different degree of obesity. We analysed data on the three factor eating questionnaire assessing cognitive restraint, disinhibition, and hunger that were filled in by 664 obese patients (469 women) who seeked treatment in our Interdisciplinary Obesity Center. Patients were divided in five BMI classes (30 - <35 kg/m(2), 35 - <40 kg/m(2), 40 - <50 kg/m(2), and >50 kg/m(2)). Multivariate regression analyses revealed that sex was significantly related to all three eating behaviour traits (all P < 0.042) but no significant relation to BMI (as a continuous variable) was observed. Women in comparison to men showed significantly higher cognitive restraint (9.7 ± 4.3 vs. 7.7 ± 4.4; P < 0.001) and disinhibition (9.0 ± 3.5 vs. 7.7 ± 3.5; P < 0.001) scores and also showed higher hunger scores (6.9 ± 3.7 vs. 6.3 ± 3.5; P = 0.042). Analyses on different BMI classes revealed that cognitive restraint decreased (P = 0.016) while disinhibition (P = 0.010) and hunger (P = 0.044) increased independently of sex with increasing BMI classes. However, above the obesity grade I class (i.e. BMI 30 - < 35 kg/m(2)) there were no differences in eating behaviour variables between the remaining BMI classes. Data indicate profound differences in eating behaviour between women and men that persist across a wide range of obesity. Furthermore, data suggest that while grade I obese patients show higher cognitive restraint and less disinhibition and hunger scores than more severe obese patients these dimensions of eating behaviour do not systematically vary across higher BMI classes.

Hypoglycemia Unawareness-A Review on Pathophysiology and Clinical Implications.

Hypoglycemia is a particular problem in people with diabetes while it can also occur in other clinical circumstances. Hypoglycemia unawareness describes a condition in which autonomic and neuroglycopenic symptoms of hypoglycemia decrease and hence are hardly perceivable. A failure to recognize hypoglycemia in time can lead to unconsciousness, seizure, and even death. The risk factors include intensive glycemic control, prior episodes of severe hypoglycemia, long duration of diabetes, alcohol consumption, exercise, renal failure, and sepsis. The pathophysiological mechanisms are manifold, but mainly concern altered brain glucose sensing, cerebral adaptations, and an impaired hormonal counterregulation with an attenuated release of glucagon, epinephrine, growth hormone, and other hormones, as well as impaired autonomous and neuroglycopenic symptoms. Physiologically, this counterregulatory response causes blood glucose levels to rise. The impaired hormonal counterregulatory response to recurrent hypoglycemia can lead to a vicious cycle of frequent and poorly recognized hypoglycemic episodes. There is a shift in glycemic threshold to trigger hormonal counterregulation, resulting in hypoglycemia-associated autonomic failure and leading to the clinical syndrome of hypoglycemia unawareness. This clinical syndrome represents a particularly great challenge in diabetes treatment and, thus, prevention of hypoglycemia is crucial in diabetes management. This mini-review provides an overview of hypoglycemia and the associated severe complication of impaired hypoglycemia awareness and its symptoms, pathophysiology, risk factors, consequences, as well as therapeutic strategies.

Real-World Use of Oral Semaglutide in Adults with Type 2 Diabetes: The PIONEER REAL Switzerland Multicentre, Prospective, Observational Study.

INTRODUCTION: Real-world data provide insight into how medications perform in clinical practice. The PIONEER REAL Switzerland study aimed to understand clinical outcomes with oral semaglutide in adults with type 2 diabetes (T2D). METHODS: PIONEER REAL Switzerland was a 34-44-week, multicentre, prospective, non-interventional, single-arm study of adults with T2D naïve to injectable glucose-lowering medication who were initiated on oral semaglutide in routine clinical practice. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline (BL) to end of study (EOS); secondary endpoints included change in body weight (BW) from BL to EOS and the proportion of participants achieving HbA1c < 7.0% and the composite endpoints HbA1c reduction ≥ 1%-points with BW reduction ≥ 3% or ≥ 5% at EOS. Safety was assessed in participants who received ≥ 1 dose of oral semaglutide. RESULTS: Of the 185 participants (female/male, n = 67/118) initiating oral semaglutide, 168 (90.8%) completed the study and 143 (77.3%) remained on treatment with oral semaglutide at EOS. At BL, participants had a mean age of 62 years, diabetes duration of 6.4 years, HbA1c of 7.7%, BW of 95.6 kg and body mass index of 33.2 kg/m2; 56.2% of participants were receiving glucose-lowering medications. Significant reductions were observed for HbA1c (estimated change - 0.91%; 95% confidence interval [CI] - 1.10, - 0.71; p < 0.0001) and BW (estimated change - 4.85%; 95% CI - 5.70, - 4.00; p < 0.0001). In total, 139 adverse events (AEs) were reported in 65 (35.1%) participants; most were mild or moderate. The most frequent AEs were gastrointestinal disorders (27.0%); 31 AEs in 20 (10.8%) participants led to discontinuation of oral semaglutide. Six serious AEs were reported; all were considered unlikely to be related to oral semaglutide. CONCLUSION: People living with T2D treated with oral semaglutide in Switzerland achieved clinically significant reductions in HbA1c and BW, with no new safety signals. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04537624. A graphical abstract is available for this article.

Early results of the Swiss Multicentre Bypass or Sleeve Study (SM-BOSS): a prospective randomized trial comparing laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass.

OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) has been proposed as an effective alternative to the current standard procedure, laparoscopic Roux-en-Y gastric bypass (LRYGB). Prospective data comparing both procedures are rare. Therefore, we performed a randomized clinical trial assessing the effectiveness and safety of these 2 operative techniques. METHODS: Two hundred seventeen patients were randomized at 4 bariatric centers in Switzerland. One hundred seven patients underwent LSG using a 35-F bougie with suturing of the stapler line, and 110 patients underwent LRYGB with a 150-cm antecolic alimentary and a 50-cm biliopancreatic limb. The mean body mass index of all patients was 44 ± 11.1 kg/m, the mean age was 43 ± 5.3 years, and 72% were female. RESULTS: The 2 groups were similar in terms of body mass index, age, sex, comorbidities, and eating behavior. The mean operative time was less for LSG than for LRYGB (87 ± 52.3 minutes vs 108 ± 42.3 minutes; P = 0.003). The conversion rate was 0.9% in both groups. Complications (<30 days) occurred more often in LRYGB than in LSG (17.2% vs 8.4%; P = 0.067). However, the difference in severe complications did not reach statistical significance (4.5% for LRYGB vs 1% for LSG; P = 0.21). Excessive body mass index loss 1 year after the operation was similar between the 2 groups (72.3% ± 22% for LSG and 76.6% ± 21% for LRYGB; P = 0.2). Except for gastroesophageal reflux disease, which showed a higher resolution rate after LRYGB, the comorbidities and quality of life were significantly improved after both procedures. CONCLUSIONS: LSG was associated with shorter operation time and a trend toward fewer complications than with LRYGB. Both procedures were almost equally efficient regarding weight loss, improvement of comorbidities, and quality of life 1 year after surgery. Long-term follow-up data are needed to confirm these facts.

Partial sleep restriction modulates secretory activity of thyrotropic axis in healthy men.

Sleep and endocrine function are known to be closely related, but studies on the effect of moderate sleep loss on endocrine axes are still sparse. We examined the influence of partial sleep restriction for 2 days on the secretory activity of the thyrotropic axis. Fifteen healthy, normal-weight men were tested in a balanced, cross-over study. Serum concentrations of thyrotrophin (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) were monitored at 1-h intervals during a 15-h daytime period (08:00-23:00 h) following two nights of restricted sleep (bedtime 02:45-07:00 h) and two nights of regular sleep (bedtime 22:45-07:00 h), respectively. Serum concentrations of fT3 (P < 0.026) and fT4 (P = 0.089) were higher after sleep restriction than regular sleep, with a subsequent blunting of TSH concentrations in the evening hours of the sleep restriction condition (P = 0.008). These results indicate profound alterations in the secretory activity of the thyrotropic axis after 2 days of sleep restriction to ~4 h, suggesting that acute partial sleep loss impacts endocrine homeostasis, with potential consequences for health and wellbeing.

Long-term outcomes after gastric bypass surgery in patients with craniopharyngioma-related hypothalamic obesity-Three cases with 7, 8, and 14 years follow-up.

INTRODUCTION: Craniopharyngioma is a brain tumor, resection which often results in hypothalamic damage leading to severe obesity. While small case series and case-control studies have shown the benefits of bariatric surgery in patients with craniopharyngioma-related hypothalamic obesity, long-term results (>5 years) have not been reported so far. METHODS: We analyzed data from 3 cases with craniopharyngioma-related hypothalamic obesity who had undergone (one proximal, two very long limb distal) Roux-en Y gastric bypass (RYGB) surgery 7, 8, and 14 years before their latest follow-up visit. RESULTS: Percentage of total weight loss varied across the 3 patients (11%, 26%, 32%). Preexisting type 2 diabetes markedly improved in 2 patients with one showing a temporary and one a persisting remission. At RYGB surgery one patient was diagnosed to have liver cirrhosis (intraoperative biopsy), but liver function remained stable or even improved during a 7-year follow-up period. One patient required proximalisation of lower anastomosis (distal RYGB) because of severe hypoproteinemia and diarrhea which resolved after revision. Another patient temporarily developed alcohol abuse that led to weight regain, but his weight decreased when alcohol consumption became under control. Importantly, all three patients stated in a standardized questionnaire that they have benefited and that they would recommend RYGB surgery to another person. CONCLUSION: Despite showing an unsatisfying weight loss result in one patient and distinct complications in the other two patients, all patients clearly showed long-term persisting benefits. Moreover, self-reported outcomes confirm that it was the right decision to recommend RYGB to our patients displaying craniopharyngioma-related hypothalamic obesity.

Impact of Albumin-to-Creatinine Ratio Point-of-Care Testing on the Diagnosis and Management of Diabetic Kidney Disease.

BACKGROUND: For the diagnosis of diabetic kidney disease (DKD), quantitative albuminuria measurement using the albumin-to-creatinine ratio (ACR) is recommended according to various guidelines. It can be measured either in specialized laboratories or using ACR point-of-care testing (POCT). This observational study aims at evaluating the effect of ACR POCT utilization on the DKD diagnosis and treatment management for glycemic control and blood pressure. METHOD: Data of 717 patients with diabetes (type 1 diabetes: n = 236; type 2 diabetes: n = 463; other diabetes forms: n = 18) were assessed in three centers. The impact of ACR POCT on DKD diagnosis and treatment management for glycemic control and blood pressure was assessed using a case report form. The assessment of ACR POCT utilization purpose and relevance for physicians was documented using a questionnaire. RESULTS: Of all participants (n = 717), 39.1% had a confirmed/suspected DKD diagnosis. Hereof, 8.6% were newly diagnosed with DKD, and 9.9% were suspected with DKD based on the actual ACR POCT values. Within the group of patients with confirmed/suspected DKD (n = 280), treatment modification was performed in 46.1% of participants. A drug initiation with GLP-1 receptor agonists or SGLT2 inhibitors was performed in 11.1% or 8.9% of patients with confirmed/suspected DKD, respectively. Regarding the utilization purposes of ACR POCT, 100% of the physicians (n = 8) indicated using it to examine patients with diabetes with or without hypertension; 75% considered it very important for patients with diabetes. CONCLUSIONS: The implementation of ACR POCT may positively affect DKD diagnosis and subsequently allow better management of patients with diabetes.