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

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). 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. 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). 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

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 Author(s) 2011. This article is published with open access at Springerlink.co

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 obesityrelated 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/m2 (5.6), 103 women) were treated with either Roux-en-Y gastric bypass surgery (nZ80) or intensive lifestyle intervention at a rehabilitation centre (nZ66). 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%, PZ0.027, and 49 vs 23%, PZ0.016. 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

Morbidly Obese Patients—Who Undergoes Bariatric Surgery?

Treatment seeking patients with severe obesity might choose between specialized medical treatment and surgical treatment. Knowledge of what distinguishes patients that choose either treatment is sparse, with greater understanding also needed on what consequences this choice has for the prevalence, remission and new onset of comorbidities, as well as for the bioavailability of drugs. This has prompted the studies in Gunn Signe Jakobsen and her coauthors work on treatment seeking patients with severe obesity focusing on the prevalence of comorbidities, changes in the use of drugs for hypertension, diabetes and dyslipidaemia, as well as changes in bioavailability of atorvastatin. The methods used in the studies in the thesis; "Bariatric surgery and specialized medical treatment for severe obesity Impact on cardiovascular risk factors and postsurgical pharmacokinetics of atorvastatin "; are a cross-sectional study, a registry based cohort study and a prospective pharmacokinetic study. The results of the studies presented were: - The type and number of comorbidities associated with morbid obesity did not necessarily impact upon choice of treatment, but there was an increased odds for choosing surgery for patients with higher BMI, younger age and earlier onset of obesity. - Patients opting for bariatric surgery as opposed to specialized medical treatment had higher odds of experiencing remission, and significantly lower odds for new-onset of drug treated hypertension, diabetes and dyslipidaemia. Bariatric surgery seemed to not only induce remission but was also effective in preventing disease. - The bioavailability of atorvastatin was increased after bariatric surgery, with a normalization in the long term. This knowledge can give a better understanding of the population of patients seeking treatment for severe obesity and should be included in the shared decision process when helping the patient identify their preferences for treatment of severe obesity in the context of their values

The Relationship Between Anthropometric Measures, Blood Gases, and Lung Function in Morbidly Obese White Subjects

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Obesity may cause adverse effects on the respiratory system. The main purpose of this study was to investigate how various measures of obesity are related to arterial blood gases and pulmonary function. Methods This is a cross-sectional study of consecutive morbidly obese patients with normal lung function. Blood gas samples were taken from the radial artery after 5 min of rest with subjects sitting upright. Lung function measurements included dynamic spirometry, static lung volumes, and gas diffusing capacity. Results The 149 patients (77 % women) had a mean (SD) age of 43 years (11 years) and BMI of 45.0 kg/m 2 (6.3 kg/m 2). The mean expiratory reserve volume (ERV) was less than half (49%) of predicted value, whilst most other lung function values were within predicted range. Forty-two patients had an abnormally low pO2 value (&lt;10.7 kPa [80 mmHg]), while eight patients had a high pCO2 value (&gt;6.0 kPa [45 mmHg])

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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 <it>t</it>-test, chi-square tests, Fisher's exact test and multiple linear regression analyses were used as statistical methods.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>Most measures of general and abdominal obesity were predictors of arterial stiffness in female morbidly obese patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT00626964">NCT00626964</a></p

Low serum creatinine is associated with type 2 diabetes in morbidly obese women and men: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Low skeletal muscle mass is associated with insulin resistance and metabolic syndrome. Serum creatinine may serve as a surrogate marker of muscle mass, and a possible relationship between low serum creatinine and type 2 diabetes has recently been demonstrated. We aimed to validate this finding in a population of Caucasian morbidly obese subjects.</p> <p>Methods</p> <p>Cross-sectional study of 1,017 consecutive morbidly obese patients with an estimated glomerular filtration rate >60 ml/min/1.73 m². Logistic regression (univariate and multiple) was used to assess the association between serum creatinine and prevalent type 2 diabetes, including statistically testing for the possibility of non-linearity in the relationship by implementation of Generalized Additive Models (GAM) and piecewise linear regression. Possible confounding variables such as age, family history of diabetes, waist-to-hip ratio, hypertension, current smoking, serum magnesium, albuminuria and insulin resistance (log HOMA-IR) were adjusted for in three separate multiple logistic regression models.</p> <p>Results</p> <p>The unadjusted GAM analysis suggested a piecewise linear relationship between serum creatinine and diabetes. Each 1 μmol/l increase in serum creatinine was associated with 6% (95% CI; 3%-8%) and 7% (95% CI; 2%-13%) lower odds of diabetes below serum creatinine levels of 69 and 72 μmol/l in women and men, respectively. Above these breakpoints the serum creatinine concentrations did not reduce the odds further. Adjustments for non-modifiable and modifiable risk factors left the piecewise effect for both women and men largely unchanged. In the fully adjusted model, which includes serum magnesium, albuminuria and log HOMA-IR, the piecewise effect for men was statistically non-significant, but it remained present for women. Patients with creatinine levels below median had approximately 50% (women) and 75% (men) increased odds of diabetes.</p> <p>Conclusions</p> <p>Low serum creatinine is a predictor of type 2 diabetes in Caucasian morbidly obese patients, independent of age, gender, family history of diabetes, anthropometric measures, hypertension, and current smoking. Longitudinal studies of both obese and non-obese populations are needed to investigate whether serum creatinine may be causally linked with type 2 diabetes, and if so, precisely how they are linked.</p

A randomized, controlled trial of 3.0 mg of liraglutide in weight management

BACKGROUND Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagonlike peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P&lt;0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P&lt;0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P&lt;0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.)