In this report from the Swedish Obese Subjects study, the rate of incident type 2 diabetes in usual-care and bariatric-surgery groups was 28.4 and 6.8 cases per 1000 person-years, respectively. These ...findings suggest that surgery is much more efficient than usual care.
Multiple studies have shown associations between obesity and type 2 diabetes
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and between changes in body weight and incident type 2 diabetes.
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It is also well established that the worldwide increase in obesity is associated with an increase in the prevalence of type 2 diabetes.
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Currently, 285 million people have type 2 diabetes, and this number is predicted to increase to 439 million by 2030.
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Among persons in a prediabetic state, the incidence of type 2 diabetes is reduced by approximately 40 to 45% with effective lifestyle changes or drug treatment,
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and the effects persist, in part, . . .
Bariatric Surgery and Long-term Cardiovascular Events Sjöström, Lars; Peltonen, Markku; Jacobson, Peter ...
JAMA : the journal of the American Medical Association,
01/2012, Letnik:
307, Številka:
1
Journal Article
Recenzirano
Odprti dostop
CONTEXT Obesity is a risk factor for cardiovascular events. Weight loss might protect against cardiovascular events, but solid evidence is lacking. OBJECTIVE To study the association between ...bariatric surgery, weight loss, and cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS The Swedish Obese Subjects (SOS) study is an ongoing, nonrandomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls who received usual care. Patients were recruited between September 1, 1987, and January 31, 2001. Date of analysis was December 31, 2009, with median follow-up of 14.7 years (range, 0-20 years). Inclusion criteria were age 37 to 60 years and a body mass index of at least 34 in men and at least 38 in women. Exclusion criteria were identical in surgery and control patients. Surgery patients underwent gastric bypass (13.2%), banding (18.7%), or vertical banded gastroplasty (68.1%), and controls received usual care in the Swedish primary health care system. Physical and biochemical examinations and database cross-checks were undertaken at preplanned intervals. MAIN OUTCOME MEASURES The primary end point of the SOS study (total mortality) was published in 2007. Myocardial infarction and stroke were predefined secondary end points, considered separately and combined. RESULTS Bariatric surgery was associated with a reduced number of cardiovascular deaths (28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group; adjusted hazard ratio HR, 0.47; 95% CI, 0.29-0.76; P = .002). The number of total first time (fatal or nonfatal) cardiovascular events (myocardial infarction or stroke, whichever came first) was lower in the surgery group (199 events among 2010 patients) than in the control group (234 events among 2037 patients; adjusted HR, 0.67; 95% CI, 0.54-0.83; P < .001). CONCLUSION Compared with usual care, bariatric surgery was associated with reduced number of cardiovascular deaths and lower incidence of cardiovascular events in obese adults.
The prospective, controlled Swedish Obese Subjects study enrolled 4047 subjects who either underwent bariatric surgery or received conventional treatment. The results of follow-up for up to 15 years ...suggest that bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality.
The results suggest that bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality.
In the United States from 1980 through 2004, the prevalence of obesity — defined as a body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) of 30 or more — doubled, rising to include more than 30% of the population.
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The majority of large and long-term epidemiologic studies have indicated that obesity is associated with increased mortality.
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The life expectancy of severely obese persons is reduced by an estimated 5 to 20 years.
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Weight loss is known to be associated with improvement of intermediate risk factors for disease,
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suggesting that weight . . .
Aims/hypothesis
Obesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investigate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy ...(SG) surgery compared with a diet low in energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the global and tissue-specific level in individuals with obesity but not diabetes.
Methods
In this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding, sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery (
n
=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (
n
=9), investigations were carried out, including an OGTT and hyperinsulinaemic–euglycaemic clamps during which concomitant simultaneous whole-body
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Ffluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change.
Results
One month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight (mean ± SD: −7.7±1.4 kg and −7.4±2.2 kg, respectively), adipose tissue volume (7%) and liver fat content (2% units). HOMA-IR, a main endpoint, was significantly reduced following OS (−26.3% 95% CI −49.5, −3.0,
p
=0.009) and non-significantly following LCD (−20.9% 95% CI −58.2, 16.5). For both groups, there were similar reductions in triglycerides and LDL-cholesterol. Fasting plasma glucose and insulin were also significantly reduced only following OS. There was an increase in glucose AUC in response to an OGTT in the OS group (by 20%) but not in the LCD group. During hyperinsulinaemia, only the OS group showed a significantly increased PET-derived glucose uptake rate in skeletal muscle but a reduced uptake in the heart and abdominal adipose tissue. Both liver and brain glucose uptake rates were unchanged after surgery or LCD. Whole-body glucose disposal and endogenous glucose production were not significantly affected.
Conclusions/interpretation
The short-term metabolic effects seen 4 weeks after OS are not explained by loss of body fat alone. Thus OS, but not LCD, led to reductions in fasting plasma glucose and insulin resistance as well as to distinct changes in insulin-stimulated glucose fluxes to different tissues. Such effects may contribute to the prevention or reversal of type 2 diabetes following OS. Moreover, the full effects on whole-body insulin resistance and plasma glucose require a longer time than 4 weeks.
Trial registration
ClinicalTrials.gov NCT02988011
Funding
This work was supported by AstraZeneca R&D, the Swedish Diabetes Foundation, the European Union’s Horizon Europe Research project PAS GRAS, the European Commission via the Marie Sklodowska Curie Innovative Training Network TREATMENT, EXODIAB, the Family Ernfors Foundation, the P.O. Zetterling Foundation, Novo Nordisk Foundation, the Agnes and Mac Rudberg Foundation and the Uppsala University Hospital ALF grants
Graphical Abstract
This study compared long-term mortality and life expectancy among patients who underwent bariatric surgery or received usual obesity care in the Swedish Obese Subjects study and in persons in the SOS ...reference study. The adjusted median life expectancy with surgery was 3.0 years longer than in control patients but 5.5 years shorter than in the general population.
Recent studies indicate that a high proportion of patients in the intensive care unit fail to attain adequate antibiotic levels. Thus, there is a need to monitor the antibiotic concentration to ...ensure effective treatment. In this article, the authors aimed to develop an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous quantification of antimicrobials to assess individualized therapeutic drug monitoring.
A UHPLC-MS/MS method with 11 antibiotics (ciprofloxacin, moxifloxacin, benzylpenicillin, levofloxacin, linezolid, rifampicin, meropenem, cloxacillin, cefotaxime, clindamycin, and piperacillin) was developed. Chromatographic separation was performed using a Kinetex Biphenyl reversed-phase column, with gradient elution using 0.1% formic acid and methanol with 0.1% formic acid. Sample preparation was performed using methanol protein precipitation. The total run time was 5 minutes.
For all analytes, the interassay inaccuracies for calibrators were ≤5%. The interday inaccuracies for the quality controls (QCs) were ≤5% for all analytes. The interassay precision for calibration standards ranged between 1.42% and 6.11%. The interassay imprecision for QCs of all antibiotics and concentrations ranged between 3.60% and 16.1%. Interassay inaccuracy and imprecision for the QCs and calibration standards were ≤15% for all drugs, except benzylpenicillin.
A rapid UHPLC-MS/MS method was developed for the simultaneous quantification of 11 different antibiotics. Minimal sample preparation was required to ensure a rapid turnaround time. The method was applied to clinical samples collected from 4 intensive care units.
Nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of advanced chronic liver disease. The progression of NAFLD, including nonalcoholic steatohepatitis (NASH), has a strong genetic ...component, and the most robust contributor is the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 encoding the 148M protein sequence variant. We hypothesized that suppressing the expression of the PNPLA3 148M mutant protein would exert a beneficial effect on the entire spectrum of NAFLD.
We examined the effects of liver-targeted GalNAc3-conjugated antisense oligonucleotide (ASO)-mediated silencing of Pnpla3 in a knock-in mouse model in which we introduced the human PNPLA3 I148M mutation.
ASO-mediated silencing of Pnpla3 reduced liver steatosis (p = 0.038) in homozygous Pnpla3 148M/M knock-in mutant mice but not in wild-type littermates fed a steatogenic high-sucrose diet. In mice fed a NASH-inducing diet, ASO-mediated silencing of Pnpla3 reduced liver steatosis score and NAFLD activity score independent of the Pnpla3 genotype, while reductions in liver inflammation score (p = 0.018) and fibrosis stage (p = 0.031) were observed only in the Pnpla3 knock-in 148M/M mutant mice. These responses were accompanied by reduced liver levels of Mcp1 (p = 0.026) and Timp2 (p = 0.007) specifically in the mutant knock-in mice. This may reduce levels of chemokine attracting inflammatory cells and increase the collagenolytic activity during tissue regeneration.
This study provides the first evidence that a Pnpla3 ASO therapy can improve all features of NAFLD, including liver fibrosis, and suppress the expression of a strong innate genetic risk factor, Pnpla3 148M, which may open up a precision medicine approach in NASH.
•ASO-mediated silencing of Pnpla3 reduced liver steatosis specifically in homozygous Pnpla3 148M/M mice fed a high-sucrose diet.•In mice fed a NASH-inducing diet this treatment reduced liver inflammation and fibrosis specifically in the Pnpla3 148M/M mutant mice.•This is the first proof of concept of a NASH precision medicine treatment exploiting an innate genetic risk variant for the disease.
Enlarged adipocytes are associated with insulin resistance and are an independent predictor of type 2 diabetes. To understand the molecular link between these diseases and adipocyte hypertrophy, we ...developed a technique to separate human adipocytes from an adipose tissue sample into populations of small cells (mean 57.6±3.54 μm) and large cells (mean 100.1±3.94 μm). Microarray analysis of the cell populations separated from adipose tissue from three subjects identified 14 genes, of which five immune-related, with more than fourfold higher expression in large cells than small cells. Two of these genes were serum amyloid A (SAA) and transmembrane 4 L six family member 1 (TM4SF1). Real-time RT-PCR analysis of SAA and TM4SF1 expression in adipocytes from seven subjects revealed 19-fold and 22-fold higher expression in the large cells, respectively, and a correlation between adipocyte size and both SAA and TM4SF1 expression. The results were verified using immunohistochemistry. In comparison with 17 other human tissues and cell types by microarray, large adipocytes displayed by far the highest SAA and TM4SF1 expression. Thus, we have identified genes with markedly higher expression in large, compared with small, human adipocytes. These genes may link hypertrophic obesity to insulin resistance/type 2 diabetes.--Jernås, M., Palming, J., Sjöholm, K., Jennische, E., Svensson, P.-A., Gabrielsson, B. G., Levin, M., Sjögren, A., Rudemo, M., Lystig, T. C., Carlsson, B., Carlsson, L. M. S., Lönn, M. Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression.
Summary Background Obesity is a risk factor for cancer. Intentional weight loss in the obese might protect against malignancy, but evidence is limited. To our knowledge, the Swedish Obese Subjects ...(SOS) study is the first intervention trial in the obese population to provide prospective, controlled cancer-incidence data. Methods The SOS study started in 1987 and involved 2010 obese patients (body-mass index BMI ≥34 kg/m2 in men, and ≥38 kg/m2 in women) who underwent bariatric surgery and 2037 contemporaneously matched obese controls, who received conventional treatment. While the main endpoint of SOS was overall mortality, the main outcome of this exploratory report was cancer incidence until Dec 31, 2005. Cancer follow-up rate was 99·9% and the median follow-up time was 10·9 years (range 0–18·1 years). Findings Bariatric surgery resulted in a sustained mean weight reduction of 19·9 kg (SD 15·6 kg) over 10 years, whereas the mean weight change in controls was a gain of 1·3 kg (SD 13·7 kg). The number of first-time cancers after inclusion was lower in the surgery group (n=117) than in the control group (n=169; HR 0·67, 95% CI 0·53–0·85, p=0·0009). The sex–treatment interaction p value was 0·054. In women, the number of first-time cancers after inclusion was lower in the surgery group (n=79) than in the control group (n=130; HR 0·58, 0·44–0·77; p=0·0001), whereas there was no effect of surgery in men (38 in the surgery group vs 39 in the control group; HR 0·97, 0·62–1·52; p=0·90). Similar results were obtained after exclusion of all cancer cases during the first 3 years of the intervention. Interpretation Bariatric surgery was associated with reduced cancer incidence in obese women but not in obese men. Funding Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Federal Government under the LUA/ALF agreement, Hoffmann La Roche, Cederoths, AstraZeneca, Sanofi-Aventis, Ethicon Endosurgery.
Context: Cell death-inducing DNA fragmentation factor-α-like effector A (CIDEA) could be a potential target for the treatment of obesity via the modulation of metabolic rate, based on the findings ...that CIDEA inhibits the brown adipose tissue uncoupling process in rodents.
Objectives: Our objects were to investigate the putative link between CIDEA and basal metabolic rate in humans and to elucidate further the role of CIDEA in human obesity.
Design: We have explored CIDEA gene expression in adipose tissue in two different human studies: a cross-sectional and population-based study assessing body composition and metabolic rate (Mölndal Metabolic study, n = 92); and a longitudinal intervention study of obese subjects treated with a very low calorie diet (VLCD) (VLCD study, n = 24).
Results: The CIDEA gene was predominantly expressed in adipocytes as compared with other human tissues. CIDEA gene expression in adipose tissue was inversely associated with basal metabolic rate independently of body composition, age, and gender (P = 0.014). The VLCD induced an increase in adipose tissue CIDEA expression (P < 0.0001) with a subsequent decrease in response to refeeding (P < 0.0001). Reduced CIDEA gene expression was associated with a high body fat content (P < 0.0001) and high insulin levels (P < 0.01). No dysregulation of CIDEA expression was observed in individuals with the metabolic syndrome when compared with body mass index-matched controls. In a separate sample of VLCD-treated subjects (n = 10), uncoupling protein 1 expression was reduced during diet (P = 0.0026) and inversely associated with CIDEA expression (P = 0.0014).
Conclusion: The findings are consistent with the concept that CIDEA plays a role in adipose tissue energy expenditure.
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