Implementation of a digital behavior change intervention (eCHANGE) for weight loss maintenance support: a service design and technology transfer approach.

Obesity is a chronic disease, and while weight loss is achievable, long-term weight loss maintenance is difficult and relapse common for people living with obesity. Aiming to meet the need for innovative approaches, digital behavior change interventions show promise in supporting health behavior change to maintain weight after initial weight loss. Implementation of such interventions should however be part of the design and development processes from project initiation to facilitate uptake and impact. Based on the development and implementation process of eCHANGE, an evidence-informed application-based self-management intervention for weight loss maintenance, this manuscript provides suggestions and guidance into; (1) How a service design approach can be used from initiation to implementation of digital interventions, and (2) How a technology transfer process can accelerate implementation of research-based innovation from idea to market.

The liver-heart axis in patients with severe obesity: The association between liver fibrosis and chronic myocardial injury may be explained by shared risk factors of cardiovascular disease.

BACKGROUND: Severe obesity is associated with increased risk of non-alcoholic fatty liver disease and cardiovascular disease. We hypothesized that liver fibrosis as quantified by the Enhanced Liver Fibrosis (ELF) test would be predictive of myocardial injury and fibrosis, expressed by higher concentrations of cardiac troponin T and I measured by high-sensitivity assays (hs-cTnT and hs-cTnI, respectively). MATERIAL AND METHODS: We performed cross-sectional analyses of baseline data from 136 patients (mean age 45 years, 38 % male) with severe obesity participating in the non-randomized clinical trial Prevention of Coronary Heart Disease in Morbidly Obese Patients (ClinicalTrials.gov NCT00626964). Associations between ELF scores, hs-cTnT, and hs-cTnI concentrations were assessed using linear regression analysis. RESULTS: ELF scores were associated with hs-cTnT in the unadjusted model (B 0.381, 95 % Confidence Interval [CI] 0.247, 0.514), but the association was attenuated upon adjustment for potential confounders (B -0.031, 95 % CI -0.155, 0.093). Similarly, for hs-cTnI, an observed association with ELF scores in the unadjusted model was attenuated upon adjustment for potential confounders ((B 0.432, 95 % CI 0.179, 0.685) and (B 0.069, 95 % CI -0.230, 0.367), respectively). Age, sex, hypertension, and estimated glomerular filtration rate were amongst the shared predictors of ELF score, hs-cTnT, and hs-cTnI that provided the univariable models with the highest R-squared and lowest Akaike Information Criterion values. CONCLUSIONS: Contrary to our hypothesis, ELF score did not predict myocardial injury and fibrosis, but we rather demonstrated an association between liver fibrosis and myocardial injury and fibrosis may be explained by shared risk factors of cardiovascular disease.

Association of time of obesity onset with comorbidities in treatment-seeking men and women with severe obesity.

OBJECTIVES: Early obesity onset is a risk factor for specific comorbidities in adulthood, but whether this relationship is present in men and women with severe obesity is unknown. This study aimed to examine whether obesity onset in childhood or adolescence, as compared with adulthood, is associated with higher odds of comorbidities in men and women with severe obesity. METHODS: A cross-sectional study of treatment-seeking men and women with severe obesity attending a tertiary care centre in Norway, from 2006 to 2017, was performed. RESULTS: A total of 4,583 participants (69.13% women) were included. Almost all men (99.69%) and women (99.18%) suffered from ≥1 comorbidities. Compared with women, men were older (mean [SD]) (45.54 [12.14] vs. 42.56 [12.00] years, p < 0.001) and had higher body mass index (44.06 [6.16] vs. 43.39 [5.80] kg m-2, p < 0.001). The most prevalent comorbidities were non-alcoholic fatty liver disease, dyslipidaemia and hypertension among men and dyslipidaemia, non-alcoholic fatty liver disease and joint pain among women. After current age and body mass index were adjusted, childhood onset of obesity (0-11 years), compared with adult onset (>20 years), was associated with lower odds (OR [95% CI]) of obstructive sleep apnoea (OSA) in men (0.69 [0.53, 0.91], p < 0.01) and higher odds of OSA (1.49 [1.16, 1.91], p < 0.01) in women, and the interaction was significant (p < 0.01). Childhood onset of obesity was also associated with higher odds of coronary heart disease in men (1.82 [1.15, 2.89], p = 0.01) and type 2 diabetes in women (1.25 [1.01, 1.54], p = 0.04). CONCLUSION: Childhood onset of obesity was associated with higher odds of coronary heart disease in men and OSA and type 2 diabetes in women, but with lower odds of OSA in men.

Effects of probiotics on body weight, body mass index, fat mass and fat percentage in subjects with overweight or obesity: a systematic review and meta-analysis of randomized controlled trials.

A systematic review and meta-analysis of randomized controlled trials was conducted to examine the effects of probiotic supplementation on body weight, body mass index (BMI), fat mass and fat percentage in subjects with overweight (BMI 25-29.9 kg m-2 ) or obesity (BMI ≥30 kg m-2 ). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for studies published between 1946 and September 2016. A meta-analysis, using a random effects model, was performed to calculate the weighted mean difference between the intervention and control groups. Of 800 studies identified through the literature search, 15 were finally included. The studies comprised a total of 957 subjects (63% women), with the mean BMI being 27.6 kg m-2 and the duration of the interventions ranging from 3 to 12 weeks. Administration of probiotics resulted in a significantly larger reduction in body weight (weighted mean difference [95% confidence interval]; -0.60 [-1.19, -0.01] kg, I2  = 49%), BMI (-0.27 [-0.45, -0.08] kg m-2 , I2  = 57%) and fat percentage (-0.60 [-1.20, -0.01] %, I2  = 19%), compared with placebo; however, the effect sizes were small. The effect of probiotics on fat mass was non-significant (-0.42 [-1.08, 0.23] kg, I2  = 84%).

The association between hyperandrogenemia and the metabolic syndrome in morbidly obese women.

BACKGROUND: Female abdominal obesity is associated with hyperandrogenemia (HA), but few studies have addressed the possible association between HA and metabolic syndrome (MetS) among obese women. Some studies indicate that insulin resistance may cause HA through different mechanisms. On the other hand, a bidirectional relationship between HA and insulin resistance has been suggested. Thus, we aimed to investigate if morbidly obese women with HA had higher odds of MetS and its components than those without HA (controls), independent of polycystic ovarian syndrome (PCOS) status. METHODS: This cross-sectional study comprised 1900 consecutive treatment seeking morbidly obese women <50 years. Free testosterone index (FTI) >0.6 defined HA. Women with previously diagnosed PCOS and those with oligo- / anovulation combined with clinical or biochemical hyperandrogenism were defined as having PCOS. Multiadjusted associations between HA and MetS were assessed by logistic regression analysis. RESULTS: Out of 1900 morbidly obese women, 1089 (57 %), 846 (45 %) and 312 (16 %) had MetS, HA and PCOS, respectively. Compared with controls (without HA), women with HA were younger (34 [1] years vs. 39 [2], p < 0.001) had a higher prevalence of MetS (62 % vs. 53 %, p < 0.001), type 2 diabetes (18 % vs. 15 %, p = 0.045), low HDL-cholesterol (65 % vs. 48 %, p < 0.001) and hypertriglyceridemia (48 % vs. 41 %, p = 0.004), but a lower prevalence of raised blood pressure (53 % vs. 59 %, p = 0.014). Multivariable analyses showed that HA was associated with increased odds of MetS (OR 1.61 [95 % CI 1.27, 2.02]), dysglycemia (1.65 [1.28, 2.11]), low HDL-cholesterol (1.58 [1.27, 1.97]), and hypertriglyceridemia (1.43 [1.15, 1.79]). After stratification for the presence of PCOS, the results remained largely unchanged in women without PCOS; MetS (1.52 [1.18, 1.96), dysglycemia (1.71 [1.30, 2.25]), low HDL-cholesterol (1.55 [1.22, 1.98]) and hypertriglyceridemia (1.36 [1.06, 1.74]). CONCLUSION: Morbidly obese women with HA had an approximately 1.5-fold increased odds of having MetS even in the absence of PCOS. Randomized controlled clinical trials, including therapeutic strategies to lower free testosterone levels, are however necessary to explore any cause-and-effect relationship.

Validation of a portable monitor for the diagnosis of obstructive sleep apnea in morbidly obese patients.

STUDY OBJECTIVES: We aimed to validate the diagnostic accuracy and night-to-night variability of a simple 3-channel (type IV monitor) portable sleep monitor, ApneaLink (AL), in a population of morbidly obese subjects. DESIGN: Cross-sectional validation and diagnostic accuracy study. SETTING: Public tertiary care obesity center in Norway. PARTICIPANTS: A total of 105 (67 females) treatment seeking morbidly obese subjects were included, mean (SD) age 44.3 (11.4) years and BMI 43.6 (5.6) kg/m2. INTERVENTIONS: The patients underwent two successive nights of recordings; the first night with the AL only, and the following night with both the reference instrument Embletta (E), a type III portable somnograph, and the AL. MEASUREMENTS AND RESULTS: Main outcomes were diagnostic accuracy of AL as assessed by sensitivity, specificity and area under ROC curves, and level of agreement between AL and E. AL had high diagnostic accuracy at all levels of OSA, and the Bland-Altman plots showed good agreement between AL and E. The sensitivity and specificity of the instrument were 93% and 71% at the AHI cutoff 5 events/h, and 94% and 94% at the AHI cutoff 15, respectively. The night-to-night variability was low. CONCLUSION: Our results indicate that a simple 3-channel portable sleep monitor (ApneaLink) has a high diagnostic accuracy in diagnosing OSA in morbidly obese treatment seeking patients. Accordingly, this and similar instruments might help non-specialists to diagnose OSA in morbidly obese patients, and, importantly, help non-specialists to refer patients who need specific treatment to specialist without unnecessary delay.

Arterial stiffness, lifestyle intervention and a low-calorie diet in morbidly obese patients-a nonrandomized clinical trial.

OBJECTIVE: Arterial stiffness is an independent predictor of cardiovascular morbidity and mortality. This study aimed to compare the 7-week effect of a low-calorie diet (LCD) and an intensive lifestyle intervention program (ILI) on arterial stiffness in morbidly obese individuals. DESIGN AND METHODS: Nonrandomized clinical trial. The LCD provided 900 kcal/day, and participants in the LCD group were instructed to maintain their habitual physical activity level. The ILI included two 90-min supervised training sessions 3 days a week at moderate to high intensity (4-8 METs) and a caloric restriction of 1000 kcal/day. RESULTS: A total of 179 individuals completed the study, 88 (56 women) in the ILI group and 91 (57 women) in the LCD group. High-fidelity applanation tonometry (Millar(®) , Sphygmocor(®) ) was used to measure carotid-femoral pulse wave velocity (PWV). After adjustment for relevant confounders, the ILI group had a significantly greater reduction in PWV than the LCD group; -0.4 (-0.6, -0.1) m/s, P = 0.004. When compared to the LCD group, the ILI group showed a larger reduction in systolic and diastolic blood pressure -5 (-9, -1) and -5 (-7, -2) mmHg, P = 0.038 and P ≤ 0.001 respectively, whereas no difference was observed regarding pulse pressure, P = 0.661. No significant differences between groups were found regarding the loss of fat mass, P = 0.259, but the loss of muscle mass was larger in the LCD group, 0.8 (0.5, 1.1) kg, P ≤ 0.001. CONCLUSION: Despite the limitations of a nonrandomized design, our findings indicate that for morbidly obese individuals a moderate caloric restriction combined with aerobic physical exercise is associated with a greater decline in PWV than a LCD alone.

Impact of OATP1B1, MDR1, and CYP3A4 expression in liver and intestine on interpatient pharmacokinetic variability of atorvastatin in obese subjects.

Individual variability in expression and function of organic anion-transporting polypeptide 1B1 (OATP1B1), multidrug resistance protein 1 (MDR1), and/or cytochrome P450 3A4 (CYP3A4) may impact the clinical response of many drugs. We investigated the correlation between expression of these proteins and pharmacokinetics of atorvastatin, a substrate of all three, in 21 obese patients with paired biopsies from liver and intestinal segments. The patients were also screened for the SLCO1B1 c.521T→C variant alleles. Approximately 30% (r(2) = 0.28) of the variation in oral clearance (CL/F) of atorvastatin was explained by hepatic OATP1B1 protein expression (P = 0.041). Patients carrying the SLCO1B1 c.521C variant allele (homozygous, n = 4; heterozygous, n = 2) exhibited 45% lower CL/F of atorvastatin than the c.521TT carriers (P = 0.067). No association between hepatic and intestinal expression of MDR1 or CYP3A4 and atorvastatin pharmacokinetics was found (P > 0.149). In conclusion, this study suggests that OATP1B1 phenotype is more important than CYP3A4 and MDR1 phenotypes for the individual pharmacokinetic variability of atorvastatin.

The effectiveness of secondary and tertiary care lifestyle intervention in morbidly obese patients: a 1-year non-randomized controlled pragmatic clinical trial.

In this non-randomized clinical pragmatic trial, we aimed to compare the effectiveness of an outpatient intensive lifestyle intervention (ILI) programme conducted in a tertiary care obesity rehabilitation centre with an outpatient moderate lifestyle intervention (MLI) programme at a secondary care obesity centre. Effectiveness was measured in terms of the 1-year effect each programme had on body weight, physical activity and health-related quality of life (HRQL). A total of 232 morbidly obese subjects were recruited to the ILI group and 140 to the MLI group, with retention rates of 78% and 44%, respectively. The ILI group had a significantly larger mean (95% confidence interval [CI]) weight loss than the MLI group, 11% (9%, 12%) vs. 2% (1%, 6%), P < 0.001, and a larger proportion of completers attaining ≥5% weight loss (71% vs. 33%), P < 0.001. Compared with the MLI group, the ILI group achieved a significant larger mean (95% CI) increase in the physical dimension of HRQL 6.9 (4.4, 9.3), P < 0.001, the mental dimension of HRQL 4.4 (1.4, 7.4), P = 0.018 and in the emotional dimension of HRQL 17.8 (12.8, 22.6), P < 0.001. There were no significant differences in terms of changes in physical activity. Compared with MLI, ILI was associated with significantly larger weight loss and better HRQL.

Pulmonary function and blood gases after gastric bypass and lifestyle intervention: a comparative study.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Impaired lung function associated with obesity improves with weight loss. WHAT THIS STUDY ADDS: This is the first study to compare the effects of obesity surgery and intensive lifestyle intervention on pulmonary function and arterial blood gases. Arterial oxygenation and pulmonary function improved to a greater extent after gastric bypass than after lifestyle intervention. The superiority of surgical treatment might be mediated by greater weight loss after gastric bypass. Impaired lung function associated with obesity improves with weight loss. The effects of obesity surgery and intensive lifestyle intervention on pulmonary function and arterial blood gases have not previously been subjected to comparative examination. In this 1-year non-randomized controlled clinical trial (ClinicalTrials.gov identifier NCT00273104), 139 morbidly obese subjects (19-66 years, mean [standard deviation] body mass index [BMI] 45.1 kg m(-2) [5.6], 107 women) were treated with either Roux-en-Y gastric bypass surgery (n = 76) or intensive lifestyle intervention (n = 63). Mean weight reduction was 30 (8)% and 8 (9)%, respectively. Dynamic and static lung volumes, gas diffusing capacity and arterial blood gases were measured. Compared with lifestyle intervention, surgery resulted in a significantly greater increase in forced vital capacity (mean [95% confidence interval] between-group difference, 7 [4-10]%), forced expiratory volume in 1 s (7 [5-9]%), total lung capacity (5 [1-8]%), vital capacity (7 [4-9]%), functional residual capacity (18 [12-24]%), expiratory reserve volume (48 [30-66]%) and partial pressure of oxygen in arterial blood (0.5 [0.0-1.0] kPa). These associations either disappeared or diminished after adjusting for weight loss. Reduced central adiposity (waist circumference and waist-to-hip ratio) and systemic inflammation (C-reactive protein and adiponectin) had no effect on pulmonary function beyond the effect of reduced general adiposity (BMI). In morbidly obese subjects, gastric bypass surgery is more effective than lifestyle intervention at improving arterial oxygenation and pulmonary function. The effect might be mediated by greater weight loss after surgical treatment.

Impact of gender on vitamin D deficiency in morbidly obese patients: a cross-sectional study.

BACKGROUND/OBJECTIVE: Obesity is associated with vitamin D deficiency (25-hydroxyvitamin D (25(OH)D) <50 nmol/l). We aimed to examine the effect of gender on vitamin D status in severe obesity. SUBJECTS/METHODS: Cross-sectional study of 2026 morbidly obese patients examined consecutively at a tertiary care centre between November 2005 and June 2010. Serum 25(OH)D concentration and use of vitamin D supplements were registered in all patients. Total vitamin D intake (µg/day) was assessed in a subgroup of 154 patients using a validated food frequency questionnaire. RESULTS: The male (n=690) and female (n=1336) patients had a mean (s.d.) age of 45.0 (12.1) years and 42.2 (12.2) years (P<0.001), body mass index (BMI) of 44.6 (6.0) kg/m(2) and 44.3 (5.9) kg/m(2) (P=0.30) and waist circumference (WC) of 140 (13) cm and 127 (13) cm (P<0.001), respectively. Male patients had significantly lower mean 25(OH)D concentrations than female patients 50.0 (22.0) nmol/l versus 53.6 (22.4) nmol/l (P=0.001) and a higher rate of vitamin D deficiency (56% versus 47%; P<0.001). Obese men had significantly higher odds of vitamin D deficiency than women (odds ratio=1.41; 95% confidence interval: 1.17-1.70, P<0.001), also after adjustment for season, age, current smoking, intake of vitamin D supplements, BMI and WC (odds ratio=1.39; 95% confidence interval: 1.10-1.76). CONCLUSIONS: Morbidly obese Norwegian men seeking weight loss treatment have significantly higher odds of vitamin D deficiency than women. Monitoring of 25(OH)D concentrations in obese patients should therefore take gender into account.

New-onset diabetes after kidney transplantation-changes and challenges.

Despite substantial improvement in short-term results after kidney transplantation, increases in long-term graft survival have been modest. A significant impediment has been the morbidity and mortality attributable to cardiovascular disease (CVD). New-onset diabetes after transplantation (NODAT) is an independent predictor of cardiovascular events. This review examines recent literature surrounding diagnosis, outcomes and management of NODAT. Amongst otherwise heterogeneous studies, a common finding is the relative insensitivity of fasting blood glucose (FBG) as a screening test. Incorporating self-testing of afternoon capillary BG and glycohemoglobin (HbA(1c) ) detects many cases that would otherwise remain undetected without the oral glucose tolerance test (OGTT). Assessing the impact of NODAT on patient and graft survival is complicated by changes to diagnostic criteria, evolution of immunosuppressive regimens and increasing attention to cardiovascular risk management. Although recent studies reinforce a link between NODAT and death with a functioning graft (DWFG), there seems to be little effect on death-censored graft loss. The significance of glycemic control and diabetes resolution for patient outcomes remain notably absent from NODAT literature and treatment is also a neglected area. This review examines new and old therapeutic options, emphasizing the need to assess ß-cell pathology in customizing therapy. Finally, areas warranting further research are considered.

The association of early post-transplant glucose levels with long-term mortality.

AIMS/OBJECTIVE: We aimed to assess the long-term effects of post-transplant glycaemia on long-term survival after renal transplantation. METHODS: Study participants were 1,410 consecutive transplant recipients without known diabetes who underwent an OGTT 10 weeks post-transplant and were observed for a median of 6.7 years (range 0.3-13.8 years). The HRs adjusted for age, sex, traditional risk factors and transplant-related risk factors were estimated. RESULTS: Each 1 mmol/l increase in fasting plasma glucose (fPG) or 2 h plasma glucose (2hPG) was associated with 11% (95% CI -1%, 24%) and 5% (1%, 9%) increments in all-cause mortality risk and 19% (1%, 39%) and 6% (1%, 12%) increments in cardiovascular (CV) mortality risk, respectively. Including both fPG and 2hPG in the multi-adjusted model the HR for 2hPG remained unchanged, while the HR for fPG was attenuated (1.05 [1.00, 1.11] and 0.97 [0.84, 1.14]). Compared with recipients with normal glucose tolerance, patients with post-transplant diabetes mellitus had higher all-cause and CV mortality (1.54 [1.09, 2.17] and 1.80 [1.10, 2.96]), while patients with impaired glucose tolerance (IGT) had higher all-cause, but not CV mortality (1.39 [1.01, 1.91] and 1.04 [0.62, 1.74]). Conversely, impaired fasting glucose was not associated with increased all-cause or CV mortality (0.79 [0.52, 1.23] and 0.76 [0.39, 1.49]). Post-challenge hyperglycaemia predicted death from any cause and infectious disease in the multivariable analyses (1.49 [1.15, 1.95] and 1.91 [1.09, 3.33]). CONCLUSIONS/INTERPRETATION: For predicting all-cause and CV mortality, 2hPG is superior to fPG after renal transplantation. Also, early post-transplant diabetes, IGT and post-challenge hyperglycaemia were significant predictors of death. Future studies should determine whether an OGTT helps identify renal transplant recipients at increased risk of premature death.

The relationship between various measures of obesity and arterial stiffness in morbidly obese patients.

BACKGROUND: Obesity is associated with increased risk of cardiovascular disease. Arterial stiffness assessed by carotid femoral pulse wave velocity (PWV) is an independent predictor of cardiovascular morbidity and mortality. We aimed to investigate how various measures of body composition affect arterial stiffness. METHODS: This is an analysis of cross-sectional baseline data from a controlled clinical trial addressing changes in arterial stiffness after either surgery or lifestyle intervention in a population of morbidly obese patients. High-fidelity applanation tonometry (Millar, Sphygmocor) was used to measure pulse wave velocity (PWV). Carotid femoral PWV is a direct measure of arterial stiffness and is considered to be the gold standard method. The Inbody 720 Body Composition Analyzer was used for bioelectrical impedance analysis (BIA). Spearman's correlation, independent samples t-test, chi-square tests, Fisher's exact test and multiple linear regression analyses were used as statistical methods. RESULTS: A total of 133 patients (79 women), with a mean (SD) age of 43 (11) years were included in the study. Men had a significantly higher prevalence of obesity related comorbidities and significantly higher PWV, 9.1 (2.0) m/s vs. 8.1 (1.8) m/s, p = 0.003, than women. In the female group, PWV was positively correlated with WC, WHtR, BMI and visceral fat area. In the male group, PWV was negatively correlated with BMI. Multiple linear regression analysis showed that increasing BMI, WC, WHtR, visceral fat area and fat mass were independently associated with higher PWV in women, but not in men, after adjustment for age, hypertension and type 2 diabetes. CONCLUSION: Most measures of general and abdominal obesity were predictors of arterial stiffness in female morbidly obese patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00626964.

Beta cell function after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention.

OBJECTIVE: The effects of various weight loss strategies on pancreatic beta cell function remain unclear. We aimed to compare the effect of intensive lifestyle intervention (ILI) and Roux-en-Y gastric bypass surgery (RYGB) on beta cell function. DESIGN: One year controlled clinical trial (ClinicalTrials.gov identifier NCT00273104). METHODS: One hundred and nineteen morbidly obese participants without known diabetes from the MOBIL study (mean (s.d.) age 43.6 (10.8) years, body mass index (BMI) 45.5 (5.6) kg/m², 84 women) were allocated to RYGB (n = 64) or ILI (n = 55). The patients underwent repeated oral glucose tolerance tests (OGTTs) and were categorised as having either normal (NGT) or abnormal glucose tolerance (AGT). Twenty-nine normal-weight subjects with NGT (age 42.6 (8.7) years, BMI 22.6 (1.5) kg/m², 19 women) served as controls. OGTT-based indices of beta cell function were calculated. RESULTS: One year weight reduction was 30% (8) after RYGB and 9% (10) after ILI (P < 0.001). Disposition index (DI) increased in all treatment groups (all P<0.05), although more in the surgery groups (both P < 0.001). Stimulated proinsulin-to-insulin (PI/I) ratio decreased in both surgery groups (both P < 0.001), but to a greater extent in the surgery group with AGT at baseline (P < 0.001). Post surgery, patients with NGT at baseline had higher DI and lower stimulated PI/I ratio than controls (both P < 0.027). CONCLUSIONS: Gastric bypass surgery improved beta cell function to a significantly greater extent than ILI. Supra-physiological insulin secretion and proinsulin processing may indicate excessive beta cell function after gastric bypass surgery.

Obesity-related cardiovascular risk factors after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention.

OBJECTIVE: Weight reduction improves several obesity-related health conditions. We aimed to compare the effect of bariatric surgery and comprehensive lifestyle intervention on type 2 diabetes and obesity-related cardiovascular risk factors. DESIGN: One-year controlled clinical trial (ClinicalTrials.gov identifier NCT00273104). METHODS: Morbidly obese subjects (19-66 years, mean (s.d.) body mass index 45.1 kg/m(2) (5.6), 103 women) were treated with either Roux-en-Y gastric bypass surgery (n=80) or intensive lifestyle intervention at a rehabilitation centre (n=66). The dropout rate within both groups was 5%. RESULTS: Among the 76 completers in the surgery group and the 63 completers in the lifestyle group, mean (s.d.) 1-year weight loss was 30% (8) and 8% (9) respectively. Beneficial effects on glucose metabolism, blood pressure, lipids and low-grade inflammation were observed in both groups. Remission rates of type 2 diabetes and hypertension were significantly higher in the surgery group than the lifestyle intervention group; 70 vs 33%, P=0.027, and 49 vs 23%, P=0.016. The improvements in glycaemic control and blood pressure were mediated by weight reduction. The surgery group experienced a significantly greater reduction in the prevalence of metabolic syndrome, albuminuria and electrocardiographic left ventricular hypertrophy than the lifestyle group. Gastrointestinal symptoms and symptomatic postprandial hypoglycaemia developed more frequently after gastric bypass surgery than after lifestyle intervention. There were no deaths. CONCLUSIONS: Type 2 diabetes and obesity-related cardiovascular risk factors were improved after both treatment strategies. However, the improvements were greatest in those patients treated with gastric bypass surgery.

Significant increase in systemic exposure of atorvastatin after biliopancreatic diversion with duodenal switch.

Biliopancreatic diversion with duodenal switch is a combined restrictive and malabsorptive surgical weight loss procedure. Given that this procedure introduces a bypass of the proximal small intestine, it is a suitable model for investigating the influence of the proximal intestine on drug bioavailability. Eight-hour pharmacokinetic profiles were obtained the day before surgery and again after surgery at (median) 6 weeks (range, 4-8 weeks) in 10 morbidly obese patients who were receiving treatment with 20-80 mg atorvastatin each morning. The bioavailability of atorvastatin acid was significantly increased, with a mean twofold higher AUC(0-8) after surgery (range 1.0-4.2, P = 0.001). Time to maximum plasma concentration (C(max)) increased from 1.2 h before surgery to 2.3 h after surgery (P = 0.03). The results emphasize the protective nature of the proximal small intestine against ingested exogenous compounds. Consequently, retitration to the lowest effective dose should be considered after biliopancreatic diversion with duodenal switch in the case of drugs with a high degree of intestinal first pass metabolism and a narrow therapeutic window.

Significantly altered systemic exposure to atorvastatin acid following gastric bypass surgery in morbidly obese patients.

The impact of gastric bypass on atorvastatin pharmacokinetics was investigated in 12 morbidly obese patients being treated with 20-80 mg atorvastatin each morning. Eight-hour pharmacokinetic investigations were performed the day before the surgery and at a median of 5 weeks (range 3-6 weeks) after the surgery. Gastric bypass surgery produced a variable effect on individual systemic exposure to atorvastatin acid (area under the plasma concentration vs. time curve from 0 to 8 h postdose (AUC(0-8))), ranging from a threefold decrease to a twofold increase (median ratio = 1.1, P = 0.99). Patients with the highest systemic exposure to atorvastatin before surgery showed reduced exposure after surgery (n = 3, median ratio = 0.4, range = 0.3-0.5, P < 0.01), whereas those with lower systemic exposure before surgery showed a median 1.2-fold increase in atorvastatin AUC(0-8) (n = 9, range = 0.8-2.3, P = 0.03) after surgery. This study indicates that the presurgical first-pass metabolic capacity influences the effect of gastric bypass on atorvastatin bioavailability. Because individual first-pass metabolic capacity is not readily assessable clinically, retitration up to the lowest effective dose should be performed after the surgery.

The impact of early-diagnosed new-onset post-transplantation diabetes mellitus on survival and major cardiac events.

The impact of early-diagnosed new-onset post-transplantation diabetes mellitus (PTDM) on cardiovascular (CV) disease is not well described. The objectives of the present prospective single-center observational study were to assess the long-term effects of early-diagnosed new-onset PTDM on major cardiac events (MCE; cardiac death or nonfatal acute myocardial infarction) and patient survival. Diabetic status and CV risk factors were assessed in 201 consecutive renal allograft recipients 3 months after transplantation (baseline) during a period of 16 months (1995-96). Follow-up data until January 1, 2004 were obtained from the Norwegian Renal Registry. The 8-year (range 7-9 years) cumulative incidence of MCEs was 7% (nine out of 138) in recipients without diabetes, 20% (seven out of 35) in patients with new-onset PTDM and 21% (six out of 28) in patients with diabetes mellitus before transplantation (DM). Proportional hazards regression analyses (forward stepwise regression) revealed that patients with PTDM had an approximately three-fold increased risk of MCEs as compared with nondiabetic patients (hazard ratio (HR)=3.27, 95% confidence interval (CI)=1.22-8.80, P=0.019). A total of 61 patients (30%) died. Eight-year patient survival was 80% in the nondiabetic group, 63% in the PTDM group and 29% in the DM group, respectively. Pretransplant diabetes (HR=5.09, 95% CI=2.60-9.96, P<0.001), age (HR=1.03, 95% CI=1.01-1.05, P=0.016), cytomegalovirus (CMV) infection (HR=2.66, 95% CI=1.27-5.53, P=0.009), and creatinine clearance (HR=0.98, 95% CI=0.96-1.00, P=0.046), but not PTDM (HR=1.20, 95% CI=0.58-2.49, P=0.621), were independent predictors of death in the multiple Cox regression model. Early-diagnosed PTDM is a predictor of MCEs, but not of all-cause mortality, the first 8 years after renal transplantation.

Asymptomatic cytomegalovirus infection is associated with increased risk of new-onset diabetes mellitus and impaired insulin release after renal transplantation.

AIMS/HYPOTHESIS: The human cytomegalovirus (CMV) may increase the risk of diabetes mellitus, but the literature is scarce. The present study was designed to test the hypothesis that asymptomatic CMV infection is associated with increased risk of new-onset diabetes after renal transplantation, and to assess the impact of asymptomatic CMV infection on OGTT-derived estimates of insulin release and insulin action. METHODS: A total of 160 consecutive non-diabetic renal transplant recipients on cyclosporine (Sandimmun Neoral)-based immunosuppression were closely monitored for CMV infection during the first 3 months after transplantation. All patients underwent a 75-g OGTT at 10 weeks. Excluded from the analyses were 36 patients with symptomatic CMV infection (disease). RESULTS: The incidence of new-onset diabetes was 6% in a control group of recipients without CMV infection (4/63) and 26% in the group with asymptomatic CMV infection (16/61). Asymptomatic CMV infection was associated with a significantly increased risk of new-onset diabetes (adjusted odds ratio: 4.00; 95% CI: 1.19 to 13.43, p=0.025). The group of patients with CMV infection had a significantly lower median insulin release than controls. CONCLUSIONS/INTERPRETATION: Our findings support the hypothesis that asymptomatic CMV infection is associated with increased risk of new-onset post-transplant diabetes mellitus, and suggest that impaired insulin release may involve one pathogenetic mechanism.