Metabolically healthy obesity: Is it really healthy for type 2 diabetes mellitus?

Metabolically healthy obese (MHO) individuals are reported to have a lower risk of developing cardiovascular diseases in comparison with individuals with metabolic syndrome. However, the association between MHO and type 2 diabetes (T2DM) is still controversial. Some studies indicated that MHO is a favorable phenotype for T2DM, but more studies showed that MHO individuals have an increased risk of developing T2DM compared with metabolically healthy normal-weight individuals, especially among those who would acquire metabolically unhealthy obesity. This has been supported by finding insulin resistance and low-grade inflammatory responses in MHO individuals with a tendency for impaired beta-cell dysfunction. Studies also showed that liver fat accumulation increased the risk of incidence of T2DM in MHO. Here, we reviewed current literature on the relationship between MHO and T2DM, discussed the determinants for the development of diabetes in MHO, and summarized the measures for the prevention of T2DM in MHO.     

Prevalence of NASH/NAFLD in people with obesity who are currently classified as metabolically healthy

BackgroundWhile metabolic health in obesity may confer a protective status, recent studies indicate that nonalcoholic fatty liver disease (NAFLD) or even nonalcoholic steatohepatitis (NASH) may exist in this category of individuals. Although cardiovascular and diabetic risks have been well described, the risk of NAFLD and NASH among this population requires further investigation.ObjectiveOur goal was to compare the prevalence of steatosis, NAFLD, and NASH between individuals with metabolically healthy obesity (MHO) and individuals with metabolically abnormal obesity (MAO) and to identify preoperative risk factors for these conditions in a prospective cohort with morbid obesity scheduled for bariatric surgery.SettingsTertiary referral university hospital in France.MethodsThe prospective cohort included 837 bariatric patients who also had an intraoperative liver biopsy between 2002 and 2015. Obese individuals fulfilling none of the criteria in the strict definition of metabolic syndrome were considered metabolically healthy. Preoperative blood samples and liver pathology examinations were reviewed. Steatosis, NAFLD, and NASH were carefully identified allowing comparison of prevalence and risk factors between the 2 cohorts.ResultsIn total, 149 patients (17.8%) had MHO and the remaining 688 (82.2%) had MAO. The cohort with MHO was significantly younger, had a significantly lower glycosylated hemoglobin, a lower homeostasis model assessment of insulin resistance, and increased C-reactive protein. In individuals with MHO, 44 patients (29.5%) had at least moderate steatosis (>33% macrovesicular steatosis) and 5.4% had NASH. Using logistic regression, waist circumference was positively associated with NASH, whereas body mass index and alanine aminotransferase were significantly associated with severe steatosis (>66%).ConclusionOur study indicates that obese individuals without metabolic syndrome may develop subclinical liver involvement. Therefore, the occurrence of NAFLD and NASH in this population needs further investigation.     

Obesity,metabolic health and omics: Current status and future directions

The growing obesity epidemic is becoming a major public health concern, and the associated costs represent a considerable burden on societies. Among the most common complications of severe obesity are the development of hypertension, dyslipidemia, type 2 diabetes, cardiovascular disease, and various types of cancer. Interestingly, some obese individuals have a favorable metabolic profile and appear to be somehow protected from the detrimental effects of excessive adipose tissue accumulation. These individuals remain normoglycemic, insulin sensitive, and hypotensive with proper blood lipid levels, despite their high body mass index and/or waist circumference. Multiple independent observations have led to the concept of the metabolically healthy obese (MHO) phenotype, yet no consensus has been reached to date regarding a universal definition or the main mechanism behind this phenomenon. Recent technological advances and the use of high-throughput analysis techniques have revolutionized different areas of biomedical research. A multi-omics approach, which is used to investigate changes at different molecular levels in an organism or tissue, may provide valuable insights into the interplay between the molecules or pathways and the roles of different factors involved in the mechanisms underlying metabolic health deterioration. The aim of this review is to present the current status regarding the use of omics technologies to investigate the MHO phenotype, as well as the results of targeted analyses conducted in MHO individuals.     

Metabolic abnormalities,but not obesity,contribute to the mildly reduced eGFR in middle-aged and elderly Chinese

Background

The role of obesity as a determinant of kidney dysfunction has not reached an agreement and the underlying reason may be due to the heterogeneity of obese phenotypes. The aim of the study was to explore the associations of different obese phenotypes with the change of estimated glomerular filtration rate (eGFR) and the roles of obesity and metabolic abnormalities in this association.

Methods

eGFR was calculated in 8,586 participants (≥40 years old). eGFR 60–90 mL/min/1.73 m² was defined as the mildly reduced eGFR. Multiple logistic regression analysis was used to determine odds ratios (ORs) for mildly reduced eGFR in the metabolically healthy obese (MHO), metabolically abnormal non-obese (MANO) and metabolically abnormal obese (MAO) groups, using the metabolically healthy non-obese (MHNO) subjects as the reference group. Meanwhile, the associations of body mass index (BMI), waist circumference (WC) and metabolic abnormalities (including hypertension, hyperglycemia and dyslipidemia) with the risk of mildly reduced eGFR were also investigated.

Results

The proportion of MHNO, MHO, MANO and MAO subjects was 8.3, 17.1, 10.1 and 64.5 %, respectively. Increased ORs were observed in MANO (OR 1.51, P = 0.014) and MAO (OR 1.47, P = 0.015) groups, after adjusting for age, gender, smoking, drinking, BMI and WC. When further adjusting for metabolic abnormalities, MANO (OR 1.24, P = 0.247) and MAO (OR 1.17, P = 0.366) subjects would not present increased risk of mildly reduced eGFR any more. Oppositely, fasting insulin (OR 1.03, P < 0.001), hyperglycemia (OR 1.25, P = 0.002) and dyslipidemia (OR 1.25, P = 0.002), but not hypertension, BMI and WC, significantly increased the risk of mildly reduced eGFR.

Conclusions

Metabolic abnormalities, but not simple obesity, may contribute to the mildly reduced eGFR in middle-aged and elderly Chinese.     

Higher risk of type 2 diabetes in young women with polycystic ovary syndrome: A 10-year retrospective cohort study

BACKGROUNDPolycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age. Over the last few decades, research studies have revealed that PCOS is strongly associated with metabolic disorders, including metabolic syndrome, obesity, insulin resistance and prediabetes. Clinical observation has shown that women with PCOS are expected to have an increased risk of developing type 2 diabetes (T2DM) in the future.AIMTo assess the hazard ratio (HR) of T2DM between women with/without PCOS.METHODSThis population-based, retrospective cohort study evaluated data retrieved from the National Health Insurance Research Database. The subjects were women with PCOS (n = 2545) identified on the basis of diagnosis, testing, or treatment codes, and women without PCOS as controls (n = 2545). The HR of T2DM between women with or without PCOS was the main outcome measure analyzed.RESULTSOur study found that, during a 10-year follow-up period, the overall incidence of T2DM was 6.25 per 1000 person-years in the PCOS group compared with 1.49 in the control group. After adjustment for potential confounding variables, the overall incidence of T2DM was higher in the PCOS group vs the control group (HR = 5.13, 95%CI: 3.51-7.48, P < 0.0001). The risk of developing T2DM subsequent to PCOS decreased with increasing diagnosis age: the adjusted HR was 10.4 in the 18–24-year age group, 5.28 in the 25-29-year age group, and 4.06 in the 29-34-year age group. However, no such significant association was noted in women older than 35 years.CONCLUSIONThese findings highlight the importance of prompting a more aggressive treatment to prevent diabetes in women diagnosed with PCOS at a young age, and, in contrast, the lessened importance of this type of intervention in women diagnosed with PCOS at a late reproductive age.     

Association between body-mass index and survival in peritoneal dialysis patients

Objective To evaluate the association between body-mass index and prognosis in peritoneal dialysis (PD) patients. Methods In this observational study of a single nephrology unit in Shanghai East Hospital, 81 incident continuous ambulatory peritoneal dialysis(CAPD) patients were included from Jan 2008 to Dec 2013, whom were followed-up by 36 months or until death. The patients were classified as underweight (BMI＜18.5kg/m2); normal weight (18.5～23.9kg/m2); overweight (24～27.9kg/m2) and obese (BMI≥28kg/m2). The patients and technique survival rates were estimated by Kaplan-Meier analysis. Cox proportional hazards analyses were used to elucidate relationship between BMI and all-cause mortality and technique failure in PD patients. Results The overall survival rate was similar between normal and overweight groups (P=0.96), but significantly lower in underweight group and obese group (P＜0.01 respectively). The overall technical survival rate of obese group was lower compare with normal group (P＜0.01). The main cause of technical failure was peritonitis (81.3%). BMI was positively correlated with albumin (r=0.24, P＜0.05), hemoglobin (r=0.56, P＜0.01), glucose(r=0.23, P＜0.05) and cholesterol (r=0.41, P＜0.01), but negatively correlated with Kt/V (r=-0.36, P＜0.01) and Ccr(r=-0.34, P＜0.01). In adjusted Cox proportional hazard mode 3, obese was independently associated with all-cause mortality (HR: 5.93, 95%CI: 1.10～31.79). Obese and peritonitis were independently associated with technical failure (HR: 10.33, 95%CI: 1.04～78.02 and HR: 2.74, 95%CI: 1.17～6.40 respectively). Conclusions Underweight and obese CAPD patients have poorer outcome. Obese CAPD patients also have lower technical survival rate. Obesity was an independent risk factor for all-cause mortality in CAPD patients.     

Can bariatric surgery improve cardiovascular risk factors in the metabolically healthy but morbidly obese patient?

BackgroundBariatric surgery has been shown to be effective in resolving co-morbid conditions even in patients with a body mass index (BMI)<35 kg/m². A question arises regarding the metabolic benefits of bariatric surgery in metabolically healthy but morbidly obese (MHMO) patients, characterized by a low cardiometabolic risk. The objective of this study was to assess the effects of bariatric surgery on cardiometabolic risk factors among MHMO and metabolically unhealthy morbidly obese (MUMO) adults.MethodsA nonrandomized, prospective cohort study was conducted on 222 severely obese patients (BMI>40 kg/m²) undergoing either laparoscopic roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy. Patients were classified as MHMO if only 1 or no cardiometabolic factors were present: high blood pressure, triglycerides, blood glucose (or use of medication for any of these conditions), decreased high-density lipoprotein-cholesterol (HDL-C) levels, and insulin resistance defined as homeostasis model assessment for insulin-resistance (HOMA-IR)> 3.29.ResultsForty-two (18.9%) patients fulfilled the criteria for MHMO. They were younger and more frequently female than MUMO patients. No differences between groups were observed for weight, BMI, waist and hip circumference, total and LDL-C. MHMO patients showed a significant decrease in blood pressure, plasma glucose, HOMA-IR, total cholesterol, LDL-C and triglycerides and an increase in HDL-C 1 year after bariatric surgery. Weight loss 1 year after bariatric surgery was similar in both groups.ConclusionEighteen percent of patients with morbid obesity fulfilled the criteria for MHMO. Although cardiovascular risk factors in these patients were within normal range, an improvement in all these factors was observed 1 year after bariatric surgery. Thus, from a metabolic point of view, MHMO patients benefited from bariatric surgery.     

Correlation of body weight and its change with albuminuria in physical examination population

Objective To study the effect of baseline weight and its change on new-onset albuminuria or increased urine albumin/creatinine ratio (ACR) in the physical examination population. Methods The subjects of this study were those who completed two or more physical examinations at the Physical Examination Center of Sichuan Provincial People's Hospital from September 1, 2013 to September 1, 2018. The general information and laboratory examination results at the first and last physical examinations were collected. According to body mass index (BMI), they were divided into normal BMI group and overweight/obese group. The differences in general clinical data and laboratory test results between the two groups were compared. The primary endpoint events were new-onset albuminuria or urine ACR increase≥30%. Stepwise multiple linear regression method was used to analyze the influencing factors for ACR increase, and Cox proportional hazard model method was used to analyze the impact of baseline weight and its change on new-onset albuminuria or ACR increase≥30%. Results A total of 1 761 physical examination subjects were included in this study. The follow-up time was (16.54±7.87) months. There were 59 patients with new-onset albuminuria, 30 patients with ACR increase≥30%, and 35 patients with albuminuria reversal. Multiple linear regression analysis showed that BMI was an independent influencing factor for ACR ( β=0.127, P＜0.001). Cox regression analysis showed that the older age (HR=1.041, 95%CI 1.018-1.064, P＜0.001), hypertension (HR=2.035, 95%CI 1.278-3.242, P=0.003), diabetes (HR=2.081, 95%CI 1.310-3.305, P=0.002) and hyperuricemia (HR=1.700, 95%CI 1.084-2.668, P=0.021) were independent influencing factors for new-onset albuminuria or ACR increase≥30%, while BMI (HR=1.053, 95%CI 0.975-1.137, P=0.191) and weight change rate (HR=1.030, 95%CI 0.972-1.092, P=0.322) were not independent influencing factors for endpoint events. Subgroup analysis indicated that overweight/obesity had interactions with age, hypertension, diabetes, and hyperuricemia, respectively (P for interaction＜0.05), and the effects of overweight/obesity on the pre-set primary endpoint events in each subgroup were basically consistent. There were interactions between weight gain and hypertension and diabetes (P for interaction＜0.05). Weight gain increased the risk of the primary endpoint events of women (HR=3.355, 95%CI 1.164-9.670, P=0.025), and the effects of overweight/obesity on the pre-set primary endpoint events of each subcomponent were basically the same (all P﹥0.05). The incidence of albuminuria reversal in the group with obvious weight loss was slightly higher than that in the group with obvious weight gain, but the difference was not statistically significant (P﹥0.05), which might be related to the small weight loss range (-6.08%±3.51%). Conclusions Overweight or obesity may increase the risk of albuminuria, and people with diabetes, hypertension, and hyperuricemia may be more likely to occur. Mild weight loss is not enough to reverse albuminuria.     

Relationship Between Obesity and Risk of Major Osteoporotic Fracture in Postmenopausal Women: Taking Frailty Into Consideration

The role of obesity in fracture risk remains uncertain and inconclusive in postmenopausal women. Our study aimed to assess the relationship between obesity and risk of major osteoporotic fracture (MOF; ie, a clinical fracture of upper arm or shoulder, hip, spine, or wrist) in postmenopausal women, after taking frailty into consideration. We used the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 5-year Hamilton cohort for this study. Frailty was measured by a frailty index (FI) of deficit accumulation at baseline. We incorporated an interaction term (obesity × FI) in the Cox proportional hazards regression model. We included 3985 women (mean age 69.4 years) for analyses, among which 29% were obese (n = 1118). There were 200 (5.02%) MOF events documented during follow-up: 48 (4.29%) in obese women and 152 (5.65%) in the nonobese group. Significant relationships between obesity, frailty, and MOF risk were found: hazard ratio (HR) = 0.72 (95% confidence interval [CI] 0.67–0.78) for those with an FI of zero regarding MOF risk among obese women, and HR = 1.34 (95% CI 1.11–1.62) per SD increase in the FI among nonobese women. The interaction term was also significant: HR = 1.16 (95% CI 1.02–1.34) per SD increase in the FI among obese women. Increased HRs were found with higher FIs regarding the relationship between obesity and MOF risk, indicating increasing frailty attenuated the protective effect of obesity. For example, although the HR for obesity and MOF risk among those who were not frail (FI = 0) was 0.72 (95% CI 0.67–0.78), among those who were very frail (FI = 0.70), the HR was 0.91 (95% CI 0.85–0.98). To conclude, after taking frailty into consideration, obesity was significantly associated with decreased risk of MOF in postmenopausal women among those who were not frail; however, increasing frailty attenuated this protective effect of obesity. Evaluating frailty status may aid in understanding of the complex relationship between obesity and fracture risk. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Association between weight loss and serum biomarkers with risk of incident cancer in the Longitudinal Assessment of Bariatric Surgery cohort

BackgroundBariatric surgery reduces cancer risk in populations with obesity. It is unclear if weight loss alone or metabolic changes related to bariatric surgery cause this effect.ObjectiveWe evaluated the relationship between surgical weight loss and serum biomarker changes with incident cancer in a bariatric surgery cohort.SettingTen U.S. clinical facilities.MethodsThe Longitudinal Assessment of Bariatric Surgery 2 (LABS-2) is a prospective multicenter cohort (n = 2458, 79% female, mean age = 46). We evaluated weight and serum biomarkers, measured preoperatively and 1 year postoperatively, as predictors for incident cancer. Associations were determined using Cox proportional hazards models adjusting for weight loss, age, sex, education, and smoking history.ResultsOver 8759 person-years of follow-up, 82 patients reported new cancer diagnosis (936 per 100,000 person-years, 95% confidence interval [CI]: 749–1156). Cancer risk was decreased by approximately 50% in participants with 20% to 34.9% total weight loss (TWL) compared with <20% TWL (hazard ratio [HR] = .49, 95%CI: .29–.83). Reduced cancer risk was observed with percent decrease from baseline for glucose (per 10%, HR = .94, 95%CI: .90–.99), proinsulin (per 20%, HR = .95, 95%CI: .93–.98), insulin (per 30%, HR = .97, 95%CI: .96–.99), and leptin (per 20%, HR = .81, 95%CI: .68–.97), and per 15% percent increase in ghrelin (HR = .94, 95%CI: .29–.83).ConclusionsAfter bariatric surgery, cancer risk is reduced >50% when weight loss exceeds 20% TWL compared with patients with <20% TWL. Weight loss alone may not explain the observed risk reduction, as improvements in diabetes, leptin, and ghrelin were associated with decreased cancer risk.     

不同BMI水平新鲜胚胎移植和全胚冷冻-首次冻融胚胎移植妊娠结局比较

目的比较不同体重指数(BMI)水平患者新鲜胚胎移植和全胚冷冻-首次冻融胚胎移植(FET)的妊娠结局。方法回顾性分析2009年1月至2018年5月于郑州大学第一附属医院生殖医学中心行首次新鲜胚胎移植(13019个周期)和全胚冷冻后首次FET(3546个周期)患者的临床资料。将研究对象按不同BMI分为正常体重组(18.5~23.9 kg/m2)、超重组(23.9~27.9 kg/m2)和肥胖组(≥28 kg/m2)。分析不同BMI水平下鲜胚移植组和FET组患者的临床特征和妊娠结局,采用多元Logistic回归分析矫正影响妊娠结局的混杂因素;主要结局指标包括临床妊娠率、活产率、流产率。结果矫正各种混杂因素后,正常体重组中,FET组的临床妊娠率、活产率显著低于鲜胚移植组,而流产风险显著高于鲜胚移植组[P<0.05;临床妊娠率:aOR=0.80(95%CI:0.71-0.91);活产率:aOR=0.77(95%CI:0.68-0.86);流产率:aOR=1.28(95%CI:1.05-1.58)];超重组中,FET组的临床妊娠率、活产率显著低于鲜胚移植组,流产风险显著高于鲜胚移植组[P<0.05;临床妊娠率:aOR=0.76(95%CI:0.61-0.94);活产率:aOR=0.74(95%CI:0.60-0.92);流产率:aOR=1.23(95%CI:0.87-0.96)];肥胖组中,鲜胚移植组和FET组间临床妊娠率、活产率及流产率比较均无显著性差异(P>0.05)。结论对于正常体重和超重人群,在无影响新鲜胚胎移植因素存在时,尽量选择新鲜胚胎移植;肥胖人群中两种移植方式则无明显差异。     

Leptin and Insulin Action in Severely Obese Women

Background: The authors investigated the interrelationships between the components of the metabolic syndrome in severe obesity. Methods: In non-diabetic, severely obese women, the degree of obesity (BMI), the insulin sensitivity (from the Homeostatic Model of Assessment, HOMA), the serum leptin concentration and the presence of dyslipidemia and arterial hypertension were evaluated. Results: In insulin-resistant patients, an overall impaired metabolic status and a greater cardiovascular risk were observed, while serum leptin concentration was higher than in the insulin-sensitive ones. Leptin levels and HOMA data correlated independent of BMI findings, while the presence of dyslipidemia and hypertension was unrelated to the other metabolic syndrome factors. Conclusion: In severely obese women, although other factors independently intervene, serum leptin has a role in developing the metabolic syndrome.     

Does Gastric Restriction Surgery Reduce the Risks of Metabolic Diseases?

Background: Certain risk factors for arteriosclerosis are associated with obesity, e.g. hypertension, insulin resistance, the high triglyceride - low HDL pattern. One aim in treating morbid obesity is to reduce these risk factors. This study was designed to follow metabolic risk factors after weight loss in 165 morbidly obese patients who underwent a gastric restriction operation. Methods and Patients: Lipid and hormone levels were analyzed before surgery and after 25, 50, 75 and 100% loss of excess weight. Mean cholesterol and triglyceride levels were normal or slightly elevated. HDL cholesterol was also normal (41 mg/dl). Thirty eight percent of the patients had elevated cholesterol and triglyceride levels. Insulin levels were measured as an indicator of potential insulin resistance, and with a mean of 21 μU/ml it was at the upper normal level. Results: After reaching 75% reduction of overweight in a mean time of 10 months, serum cholesterol levels were unchanged. Serum triglycerides, however, decreased by 35% (P < 0.0001) and HDL cholesterol increased by 24% (P < 0.0001). Insulin levels decreased to 8 μU/ml (P < 0.0001). Conclusion: We found an amelioration in the metabolic parameters in 75% of the patients. Nevertheless morbidly obese patients were found to have fewer abnormalities in lipid and glucose metabolism than expected from data of overweight patients with metabolic syndrome. Further long-term studies with careful evaluation of the metabolic parameters as risk factors in patients with morbid obesity need to be performed. ? 1998 Rapid Science Ltd.     

Esophageal cancer after sleeve gastrectomy: a population-based comparative cohort study

BackgroundSleeve gastrectomy (SG) is the most common bariatric surgery; however, this approach may induce gastroesophageal reflux disease (GERD). Both obesity and GERD are independent risk factors for esophageal cancer, however the impact of SG on risk of esophageal cancer remains unknown.ObjectiveTo evaluate the risk of esophageal cancer after reflux-prone bariatric surgery.SettingPopulation-level, provincial administrative healthcare database, Quebec, Canada.MethodsWe identified a population-based cohort of all patients with obesity who underwent reflux-prone surgery (SG and duodenal switch [DS]) or reflux-protective Roux-en-Y gastric bypass (RYGB) during 01/2006–12/2012 in Quebec, Canada. For every surgical patient, 2-3 nonsurgical controls with obesity matched for age, sex, and geography were also identified. Crude incidence rate ratios (IRRs) for esophageal cancer were calculated using person-time analysis. Hazard ratios (HRs) were obtained using multivariate cox regression.ResultsA total of 4121 patients had reflux-prone procedures and 852 underwent RYGB. At a mean follow-up of 7.6 years, 8 cases of esophageal cancer were identified after bariatric surgery. Compared with RYGB, IRR for esophageal cancer in reflux-prone group was 1.45 (95%CI: .19–65.5) and HR = .83 (95%CI: .10–7.27). The crude incidence rate of esophageal cancer in the reflux-prone group was higher than that of nonsurgical controls (n = 12,159; IRR = 3.46, 95%CI: 1.00–12.5), but after adjustment the difference disappeared (HR = 2.47, 95%CI: .82–7.45).ConclusionsLong-term incidence of esophageal cancer after reflux-prone bariatric surgery is not greater than RYGB. While crude incidence of esophageal cancer after reflux-prone surgery is higher than in nonsurgical patients with obesity, such difference disappears after accounting for confounders. Given the low incidence of esophageal cancer and slow progression of dysplastic Barrett esophagus, studies with longer follow-up are needed.     

Patients with clinically metabolically healthy obesity are not necessarily healthy subclinically: further support for bariatric surgery in patients without metabolic disease?

Background

Nonalcoholic fatty liver disease (NAFLD) increases the risk of liver cirrhosis and hepatocellular carcinoma and is also strongly correlated with extrahepatic diseases, including cardiovascular disease and type 2 diabetes. This risk of NAFLD among obese individuals who are otherwise metabolically healthy is not well characterized.

DNA Methylation GrimAge and Incident Diabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

DNA methylation (DNAm)-based biological age (epigenetic age) has been suggested as a useful biomarker of age-related conditions including type 2 diabetes (T2D), and its newest iterations (GrimAge measurements) have shown early promise. In this study, we explored the association between epigenetic age and incident T2D in the context of their relationships with obesity. A total of 1,057 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were included in the current analyses. We stratified the participants into three groups: normal weight, overweight, and obese. A 1-year increase of GrimAge was associated with higher 10-year (study years 15–25) incidence of T2D (odds ratio [OR] 1.06, 95% CI 1.01–1.11). GrimAge acceleration, which represents the deviation of GrimAge from chronological age, was derived from the residuals of a model of GrimAge and chronological age, and any GrimAge acceleration (positive GrimAA: having GrimAge older than chronological age) was associated with significantly higher odds of 10-year incidence of T2D in obese participants (OR 2.57, 95% CI 1.61–4.11). Cumulative obesity was estimated by years since obesity onset, and GrimAge partially mediated the statistical association between cumulative obesity and incident diabetes or prediabetes (proportion mediated = 8.0%). In conclusion, both older and accelerated GrimAge were associated with higher risk of T2D, particularly among obese participants. GrimAge also statistically mediated the associations between cumulative obesity and T2D. Our findings suggest that epigenetic age measurements with DNAm can potentially be used as a risk factor or biomarker associated with T2D development.     

Pilot Study Examining the Frequency of Several Gene Polymorphisms in a Morbidly Obese Population

Background: Obesity is a growing problem and is associated with numerous medical conditions. Several polymorphisms have been associated with lipid metabolism and obesity: PPARγ2-Pro115Gln, PPARγ2-Pro12Ala, β3AR-Trp64Arg and SR-BI IVS5 C>T. We examined the frequency of these polymorphisms in patients with a BMI>40 and compared them to individuals with a BMI<30. Our hypothesis was that these polymorphisms would occur more frequently in the obese population. Methods: This case-control study examined 126 individuals with a BMI>40 in the McGill University Health Centre Bariatric Surgery Program and 102 individuals (controls) with a BMI<30 attending a Lipid Clinic. DNA was extracted from whole blood by standard techniques. The polymorphisms were determined by polymerase chain reaction (PCR) and restriction genotyping. Results: A significant difference between controls and the morbidly obese group was observed for 2 of 4 polymorphisms.The carrier frequency for PPARγ2-Pro12Ala was 24.8% in the obese group and 12.9% in controls (odds ratio = 2.2; 95%CI = 1.1-4.4; P=0.02). The carrier frequency for SR-BI IVS5 C>T was 22.8% in obese individuals versus 8.1% in controls (odds ratio = 3.5; 95%CI = 1.6-7.7; P=0.002). There were no differences in frequency of diabetes in both obese (13/104) and control (9/126) groups (odds ratio = 1.86, 95%CI= 0.76<O.R.<4.54, P=0.184). Conclusions: These results underscore the rela tionship between gene polymorphisms and obesity. Obese individuals may differ from non-obese individuals in the gene polymorphisms associated with metabolic control.     

Visceral Obesity and Colorectal Cancer: Are We Missing the Boat with BMI?

Introduction

Compared to subcutaneous fat, visceral fat is more metabolically active, leading to chronic inflammation and tumorigenesis. The aim of this study is to describe the effect of visceral obesity on colorectal cancer outcomes using computed tomography (CT) imaging to measure visceral fat.

Materials and Methods

We conducted a retrospective chart review of patients who underwent surgical resection for colorectal cancer. Visceral fat volume was measured by preoperative CT scans. Final analysis was performed by stratifying patients based on oncologic stage.

Results

Two hundred nineteen patients met the inclusion criteria, 111 viscerally obese and 108 nonobese. Body mass index (BMI) weakly correlated with visceral fat volume measurements (R ²?=?0.304). Whereas obese patients had no difference in survival when categorizing obesity by BMI, categorizing based on visceral fat volume resulted in significant differences in stage II and stage III patients. In stage II cancer, viscerally obese patients had a nearly threefold decrease in disease-free survival (hazard ratio (HR)?=?2.72; 95 % confidence interval (CI)?=?1.21, 6.10). In stage III cancer, viscerally obese patients had a longer time to recurrence (HR?=?0.39; 95 % CI?=?0.16, 0.99).

Conclusion

This study shows that viscerally obese patients with stage II colorectal cancer are at higher risk for poor outcomes and should be increasingly considered for adjuvant chemotherapy.     

肥胖与产妇分娩镇痛中局麻药用药量的相关性

目的 探讨产妇肥胖与硬膜外分娩镇痛中局麻药用药量的相关性,为肥胖产妇分娩镇痛提供参考.方法 回顾性分析2018年9月至2019年12月于本院接受硬膜外分娩镇痛产妇,年龄21～35岁,BMI 18.5～40.0 kg/m2,ASAⅠ或Ⅱ级,根据产妇BMI分为非肥胖(18.5～29.9 kg/m2)和肥胖(BMI≥30 k...     

The effect of obesity on mid-term survival following coronary artery bypass surgery.

OBJECTIVE: Several studies have shown no significantly increased risk of in-hospital mortality for obese patients after coronary artery bypass grafting (CABG). However, the effect of obesity on mid-term survival has not been adequately studied. We set out to examine whether mid-term survival following CABG is affected by obesity. METHODS: We performed a retrospective study of 4713 consecutive patients undergoing isolated CABG between April 1997 and September 2001. Body mass index (BMI) was used as the measure of obesity, with 3429 patients categorised as non-obese (BMI<30 kg/m(2)), and 1284 patients as obese (BMI> or = 30 kg/m(2)). Patient records were linked to the National Strategic Tracing Service, which records all deaths in the community, to establish current vital status. Deaths occurring over time were described using Kaplan-Meier techniques. To control for differences in patient characteristics, we used Cox proportional hazards analysis to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Three hundred and thirty (7.0%) deaths occurred during the study period, with a mean follow-up of 2.4+/-1.4 years. The crude HR of mid-term mortality for obese patients was 1.09 (95% CI 0.86-1.39; P=0.457). After adjustment for core pre-operative factors, the adjusted HR of mid-term mortality for obese patients was 1.28 (95% CI 1.01-1.64; P=0.048). The adjusted freedom from death in the obese patients at 30 days, 1, 2, 3, and 4 years was 97.9, 95.9, 94.2, 92.4 and 90.5%, respectively, compared with 98.4, 96.8, 95.5, 94.0 and 92.5% for the non-obese patients. CONCLUSIONS: Although in-hospital mortality after CABG does not seem to be adversely affected by obesity there appears to be a significant increase in mortality in obese patients during a 4-year follow-up period.