Dag Hofsø

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/m2 (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.

Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: A cross-sectional study

BackgroundThe prevalence of vitamin D insufficiency and secondary hyperparathyroidism is high among morbidly obese subjects. Further, low serum levels of 25-hydroxyvitamin D (25 [OH]D) and magnesium have been associated with increased risk of the metabolic syndrome (MS), and recently, a possible link between PTH and MS has been reported. Although it is well known that the synthesis and secretion of PTH is regulated by serum levels of calcium, phosphate, magnesium and 25(OH)D, less is known about the possible clustered affiliation of these parameters with MS. We aimed to explore whether MS is associated with abnormal serum levels of PTH, 25(OH)D and magnesium in a population of morbidly obese patients.MethodsFasting serum levels of 25(OH)D, PTH and magnesium were assessed in a cross-sectional cohort study of 1,017 consecutive morbidly obese patients (68% women). Multiple logistic regression analyses were used to assess the independent effect of PTH, 25(OH)D and magnesium on the odds for MS (National Cholesterol Education Program [NCEP]) after adjustment for confounding factors.ResultsSixty-eight percent of the patients had MS. Patients with MS had lower mean serum magnesium (P < 0.001) and higher mean PTH (P = 0.067) than patients without MS, whereas mean 25(OH)D did not differ significantly. Patients with PTH levels in the second to fourth quartiles had higher odds of prevalent MS (odds ratio 1.47 [95% CI 0.92–2.35], 2.33 [95% CI 1.40–3.87] and 2.09 [95% CI 1.23–3.56], respectively), after adjustment for 25(OH)D, magnesium, calcium, phosphate, creatinine, age, gender, season of serum sampling, BMI, current smoking, albuminuria, CRP, insulin resistance and type 2 diabetes. Further, PTH was significantly correlated with systolic and diastolic pressure (both P < 0.001), but not with the other components of MS. The levels of 25(OH)D and magnesium were not associated with MS in the multivariate model.ConclusionThe PTH level, but not the vitamin D level, is an independent predictor of MS in treatment seeking morbidly obese Caucasian women and men. Randomized controlled clinical trials, including different therapeutic strategies to lower PTH, e.g. calcium/vitamin D supplementation and weight reduction, are necessary to explore any cause-and-effect relationship.

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

BackgroundObesity 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.MethodsThis 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). Spearmans correlation, independent samples t-test, chi-square tests, Fishers exact test and multiple linear regression analyses were used as statistical methods.ResultsA 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.ConclusionMost measures of general and abdominal obesity were predictors of arterial stiffness in female morbidly obese patients.Trial registrationClinicalTrials.gov Identifier NCT00626964

Inflammatory mediators in morbidly obese subjects: associations with glucose abnormalities and changes after oral glucose.

OBJECTIVE To explore inflammatory mediators in morbidly obese (MO) subjects with various categories of glucose tolerance and to study the changes in these mediators after an oral glucose load. DESIGN Cross-sectional and experimental study. METHODS A total of 144 MO subjects were classified into three categories: normal glucose tolerance (NGT); pre-diabetes; and new onset diabetes mellitus (NODM) were included, as were 27 normal weight normoglycemic controls. Serum osteoprotegerin (OPG), visfatin, leptin, adiponectin, interleukin-1 receptor antagonist (IL-1Ra), and C-reactive protein (CRP) were analyzed during an oral glucose tolerance test (OGTT). RESULTS Fasting levels of leptin and IL-1Ra were consistently higher in obese persons (P<0.001 and P<0.05). MO subjects with NGT had higher CRP levels (P<0.001) and lower adiponectin levels (P<0.05) compared to controls. Yet when compared with MO subjects with NODM, those with NGT had lower CRP levels and higher adiponectin levels (both P<0.05). Baseline OPG and visfatin levels did not differ between the groups (P=0.326 and P=0.198). During OGTT, OPG levels decreased (P<0.001) and visfatin levels increased transiently (P=0.018). The response in OPG and visfatin did not differ between the groups (P=0.690 and P=0.170). There were minor changes in adiponectin and leptin levels. CONCLUSIONS Morbid obesity and glucose intolerance were associated with lower adiponectin levels and higher CRP levels, thus supporting a relationship between obesity, glucose homeostasis, and inflammation. Oral glucose suppressed OPG levels and transiently enhanced visfatin levels independent of obesity and glucose tolerance status, indicating that glucose may be involved in the acute regulation of these proteins.

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.

Vitamin status after gastric bypass and lifestyle intervention: a comparative prospective study

BACKGROUND Bariatric surgery can lead to vitamin deficiencies. We aimed to assess the changes in blood vitamin concentrations in patients who were taking predefined supplements after gastric bypass surgery. METHODS A total of 29 patients underwent gastric bypass and 24 unmatched controls underwent lifestyle intervention in a prospective, nonrandomized trial. The patients in the surgical group received multivitamin, iron, calcium, vitamin D, and vitamin B(12) supplements. No supplements were prescribed to the lifestyle group. The median body mass index decreased from 46 to 32 kg/m(2) after surgery and from 40 to 39 kg/m(2) after lifestyle intervention. RESULTS Of the 53 included patients, 50 completed the 1-year follow-up examination (94%). Compared with the lifestyle patients, the surgical patients had increased vitamin B(6), folic acid, vitamin B(12), and lipid-adjusted vitamin E (P <.02 for each) concentrations but decreased vitamin A concentrations (P <.01) during follow-up. No significant difference between the 2 groups was found for vitamin B(1), vitamin C, or 25-hydroxyvitamin D. Most surgical patients reported taking their supplements. CONCLUSION Gastric bypass patients adhering to a set of dietary supplements had mostly stable or increased vitamin concentrations compared with both their baseline values and the changes in a nonsurgical control group.

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/m2 and 44.3 (5.9) kg/m2 (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.

Type 2 diabetes and pre-diabetes are associated with obstructive sleep apnea in extremely obese subjects: A cross-sectional study

BackgroundObstructive sleep apnea (OSA) is a common yet underdiagnosed condition. The aim of our study is to test whether prediabetes and type 2 diabetes are associated with obstructive sleep apnea (OSA) in extremely obese (BMI ≥ 40 kg/m2) subjects.MethodsOne hundred and thirty seven consecutive extremely obese patients (99 females) from a controlled clinical trial [MOBIL-study (Morbid Obesity treatment, Bariatric surgery versus Intensive Lifestyle intervention Study) (ClinicalTrials.gov number NCT00273104)] underwent somnography with Embletta® and a 2-hour oral glucose tolerance test (OGTT). OSA was defined by an apnea-hypopnea index (AHI) ≥ 5 events/hour. Patients were categorized into three groups according to criteria from the American Diabetes Association: normal glucose tolerance, pre-diabetes and type 2 diabetes. Multiple logistic regression analysis was used to identify possible determinants of OSA.ResultsThe patients had a mean (SD) age of 43 (11) years and a body mass index (BMI) of 46.9 (5.7) kg/m2. Males had significantly higher AHI than females, 29 (25) vs 12 (17) events/hour, p < 0.001. OSA was observed in 81% of men and in 55% of women, p = 0.008. Twenty-nine percent of subjects had normal glucose tolerance, 42% had pre-diabetes and 29% had type 2 diabetes. Among the patients with normal glucose tolerance 33% had OSA, while 67% of the pre-diabetic patients and 78% of the type 2 diabetic patients had OSA, p < 0.001. After adjusting for age, gender, BMI, high sensitive CRP and HOMA-IR, both pre-diabetes and type 2 diabetes were still associated with OSA, odds ratios 3.18 (95% CI 1.00, 10.07), p = 0.049 and 4.17 (1.09, 15.88), p = 0.036, respectively. Mean serum leptin was significantly lower in the OSA than in the non-OSA group, while other measures of inflammation did not differ significantly between groups.ConclusionsType 2 diabetes and pre-diabetes are associated with OSA in extremely obese subjects.Trial registrationMOBIL-study (Morbid Obesity treatment, Bariatric surgery versus Intensive Lifestyle intervention Study) (ClinicalTrials.gov number NCT00273104)

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

BackgroundLow 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.MethodsCross-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.ResultsThe 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.ConclusionsLow 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.

Obstructive Sleep Apnea after Weight Loss: A Clinical Trial Comparing Gastric Bypass and Intensive Lifestyle Intervention

INTRODUCTION Few studies have compared the effect of surgical and conservative weight loss strategies on obstructive sleep apnea (OSA). We hypothesized that Roux-en-Y gastric bypass (RYGB) would be more effective than intensive lifestyle intervention (ILI) at reducing the prevalence and severity of OSA (apnea-hypopnea-index [AHI] ≥ 5 events/hour). METHODS A total of 133 morbidly obese subjects (93 females) were treated with either a 1-year ILI-program (n = 59) or RYGB (n = 74) and underwent repeated sleep recordings with a portable somnograph (Embletta). RESULTS Participants had a mean (SD) age of 44.7(10.8) years, BMI 45.1(5.7) kg/m(2), and AHI 17.1(21.4) events/hour. Eighty-four patients (63%) had OSA. The average weight loss was 8% in the ILI-group and 30% in the RYGB-group (p < 0.001). The mean (95%CI) AHI reduced in both treatment groups, although significantly more in the RYGB-group (AHI change -6.0 [ILI] vs -13.1 [RYGB]), between group difference 7.2 (1.3, 13.0), p = 0.017. Twenty-nine RYGB-patients (66%) had remission of OSA, compared to 16 ILI-patients (40%), p = 0.028. At follow-up, after adjusting for age, gender, and baseline AHI, the RYGB-patients had significantly lower adjusted odds for OSA than the ILI-patients-OR (95% CI) 0.33 (0.14, 0.81), p = 0.015. After further adjustment for BMI change, treatment group difference was no longer statistically significant-OR (95% CI) 1.31 (0.32, 5.35), p = 0.709. CONCLUSION Our study demonstrates that RYGB was more effective than ILI at reducing the prevalence and severity of OSA. However, our analysis also suggests that weight loss, rather than the surgical procedure per se, explains the beneficial effects.