Association between fat mass and mortality: analysis of Mendelian randomization and lifestyle modification.

BACKGROUND: The association between fat mass and mortality has been equivocally shown to be linear, J-shaped, and U-shaped. We aimed to clarify this relationship based on Mendelian randomization (MR) analysis and lifestyle modification. METHODS: This prospective analysis included 449,831 participants from UK Biobank. Linear MR analysis was used to estimate the linear relationship between fat mass and mortality. We assessed whole body fat mass by bioimpedance analysis at baseline and categorized subjects into five equal groups based on fat mass index (FMI). The association between FMI and mortality were investigated among whole population and in subgroups stratified by individual lifestyle factors, including diet, physical activity, smoking, alcohol, sleep and psychological health. FINDINGS: Linear MR analyses indicated a positive association between genetically predicted fat mass and all-cause mortality (HR 1.10, 95 % CI 1.08-1.12, P < 0.001). The association between FMI and all-cause mortality was manifested as J-shaped (HRs across FMI categories: 1.04, 1.00, 1.07, 1.21, 1.54), which was significantly modified by the number of low-risk lifestyle factors (P for interaction<0.001). When evaluating individual lifestyle factors, we observed a nonlinear relationship between FMI and all-cause mortality among participants who had high-risk lifestyle factors, while a linear relationship was observed among participants who had low-risk lifestyle factors, especially for those with adequate physical activity (HRs across FMI categories: 0.95, 1.00, 1.05, 1.17, 1.44) and who never smoked (0.96, 1.00, 1.03, 1.14, 1.51). INTERPRETATION: Genetically determined fat mass is causally and linearly associated with mortality. The J-shape association between anthropometric FMI and mortality is caused by high-risk lifestyle factors.

Lifestyle and chronic kidney disease: A machine learning modeling study.

Background: Individual lifestyle varies in the real world, and the comparative efficacy of lifestyles to preserve renal function remains indeterminate. We aimed to systematically compare the effects of lifestyles on chronic kidney disease (CKD) incidence, and establish a lifestyle scoring system for CKD risk identification. Methods: Using the data of the UK Biobank cohort, we included 470,778 participants who were free of CKD at the baseline. We harnessed the light gradient boosting machine algorithm to rank the importance of 37 lifestyle factors (such as dietary patterns, physical activity (PA), sleep, psychological health, smoking, and alcohol) on the risk of CKD. The lifestyle score was calculated by a combination of machine learning and the Cox proportional-hazards model. A CKD event was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m2, mortality and hospitalization due to chronic renal failure, and self-reported chronic renal failure, initiated renal replacement therapy. Results: During a median of the 11-year follow-up, 13,555 participants developed the CKD event. Bread, walking time, moderate activity, and vigorous activity ranked as the top four risk factors of CKD. A healthy lifestyle mainly consisted of whole grain bread, walking, moderate physical activity, oat cereal, and muesli, which have scored 12, 12, 10, 7, and 7, respectively. An unhealthy lifestyle mainly included white bread, tea >4 cups/day, biscuit cereal, low drink temperature, and processed meat, which have scored -12, -9, -7, -4, and -3, respectively. In restricted cubic spline regression analysis, a higher lifestyle score was associated with a lower risk of CKD event (p for linear relation < 0.001). Compared to participants with the lifestyle score < 0, participants scoring 0-20, 20-40, 40-60, and >60 exhibited 25, 42, 55, and 70% lower risk of CKD event, respectively. The C-statistic of the age-adjusted lifestyle score for predicting CKD events was 0.710 (0.703-0.718). Conclusion: A lifestyle scoring system for CKD prevention was established. Based on the system, individuals could flexibly choose healthy lifestyles and avoid unhealthy lifestyles to prevent CKD.

Early-phase insulin hypersecretion associated with weight loss outcome after LSG: a prospective cohort study in Asian patients with BMI ≥28 kg/m2.

BACKGROUND: Obesity has become a global problem that poses a serious threat to human health. Laparoscopic sleeve gastrectomy (LSG) is an effective long-term treatment. However, the weight loss of some patients after LSG is still insufficient. It is necessary to investigate the factors associated with inadequate weight loss after LSG. OBJECTIVE: The objective of this study was to explore whether preoperative insulin secretion could be associated with weight loss after LSG in patients with obesity. SETTING: This is a single-center prospective cohort study conducted in a university hospital. METHODS: Patients from a prospective database who underwent LSG were analyzed. All 178 participants underwent a 75-g oral glucose tolerance test (OGTT) to assess preoperative insulin and c-peptide secretion before LSG. The areas under the curve (AUCs) for glucose, insulin, and c-peptide were determined in the OGTT. The percentage of excess weight loss (%EWL) and the percentage of total weight loss (%TWL) were used to estimate the effect of weight loss after LSG. Regression models were used to assess the correlation between preoperative insulin and c-peptide secretion with %EWL ≥75% and TWL ≥35% at 12 months after LSG. RESULTS: The AUCs of insulin and c-peptide were significantly lower in the %EWL ≥75% and %TWL ≥35% groups at 0-30 minutes, 0-60 minutes, and 0-120 minutes during the OGTT. At 30, 60, and 120 minutes during the OGTT, c-peptide levels were significantly lower in the %EWL ≥75% group and %TWL ≥35% group. The preoperative c-peptide level at 30 minutes during the OGTT (C30) was significantly negatively correlated with %EWL (ß = -.37, P < .001) and %TWL (ß = -.28, P = .011). Univariate logistic regression analysis showed that preoperative C30 was associated with %EWL ≥75% and %TWL ≥35% after LSG. According to multiple logistic regression analysis, patients with a low preoperative C30 had an 8-fold higher %TWL ≥35% after LSG than those with a high C30 (odds ratio: 8.41 [95% confidence interval: 1.46-48.58], P = .017). Similarly, patients with a low preoperative C30 had a 7-fold higher EWL% ≥75% after LSG than patients with a high C30 (odds ratio: 7.25 [95% confidence interval: 1.11-47.50], P = .039). CONCLUSIONS: The rate of weight loss after LSG is low among patients with preoperative hyperinsulinemia. The preoperative c-peptide level at 30 minutes during the OGTT is associated with weight loss after LSG.

Serum cell-free DNA and progression of diabetic kidney disease: a prospective study.

AIMS: Cell-free DNA (cfDNA) is associated with diabetes and cardiovascular diseases. Our study was to evaluate whether serum cfDNA could predict the progression of diabetic kidney disease (DKD). METHODS: In this prospective study, a total of 160 patients with DKD were enrolled, and the kidney function was followed up by measurement of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) for three consecutive years. At baseline, concentrations of serum cfDNA were measured. DKD progression was defined as two-continuous decrease in eGFR and changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at last follow-up. Regression models were used to analyze associations of serum cfDNA with the DKD progression. RESULTS: In total, 131 patients finished all the follow-up visits. At the end of the study, 64 patients showed decreased eGFR and 29 patients had changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at follow-up. At baseline, the progression group had higher serum cfDNA levels than the non-progression group (960.49 (816.53, 1073.65) ng/mL vs 824.51 (701.34, 987.06) ng/mL, p=0.014). Serum cfDNA levels were significantly negatively associated with the 1.5-year eGFR change (r=-0.219 p=0.009) and 3-year eGFR change (r=-0.181, p=0.043). Multivariate logistic analyses showed that after adjustment of age, gender, body mass index, fast plasma glucose, smoking, triglycerides, total cholesterol, duration of diabetes, systolic blood pressure, diabetic retinopathy, eGFR, high sensitivity C-reactive protein, angiotensin receptor blocker/ACE inhibitor usage, with the increase of one SD of serum cfDNA levels, the risk of DKD progression increased by 2.4 times (OR, 2.46; 95% CI 1.84 to 4.89). CONCLUSION: Serum cfDNA is closely associated with DKD, and it might be a predictor of DKD progression in patients with type 2 diabetes.

Prevalence of low lean mass in patients with adult growth hormone deficiency with or without low-dose growth hormone therapy.

OBJECTIVE: The importance of muscle mass has been emphasized in various studies, and growth hormone (GH) deficiency is tightly associated with lean mass loss. Therefore, we aimed to investigate the prevalence of low lean mass in patients with adult growth hormone deficiency (AGHD) who received or did not receive GH therapy. METHODS: In this retrospective study, we included patients diagnosed with AGHD by using the insulin tolerance test (ITT) in our hospital. Patients without completed follow-up data were excluded, and data for 56 patients were analysed. Twenty-six patients who had received GH therapy for more than 6 months, based on the medical record, were included in the GH group and received recombinant human growth hormone (rhGH) at a dose of 0.5 IU/d. Thirty patients who had not previously received GH treatment were included in the non-GH group. Many anthropometric and blood biochemical indicators were measured. Body composition was measured on a dual-energy X-ray-absorptiometry (DXA) scanner. Low lean mass was defined as a skeletal muscle index (SMI) <7.0 kg/m2 in males or 5.7 kg/m2 in females. Statistical analyses were performed using GraphPad Prism 5.0. RESULTS: Compared to the non-GH group, the patients who received GH therapy had significantly lower total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and fasting plasma glucose (FPG). The percentage of patients with low lean mass in GH and non-GH groups was 30.77% and 60%, respectively. The percentage of total lean was lower in the GH group than in the non-GH group, but the difference in total lean mass was not statistically significant. Conversely, patients with GH treatment had significantly lower fat mass and percentage than non-GH-treated patients (P < 0.05). The GH group had significantly higher serum levels of both IGF-1 and IGFBP3. Moreover, both IGF-1 and IGFBP3 were significantly correlated with SMI (r2  = 0.275, P = 0.003, and r2  = 0.138, P = 0.005, respectively). CONCLUSIONS: Our data showed that AGHD patients who received low-dose GH treatment had a lower prevalence of low lean mass than those who did not receive GH treatment. Patients with GH treatment had significantly lower cardiovascular risk factors, especially the lipid profile.

The effectiveness and safety of laparoscopic sleeve gastrectomy with different sizes of bougie calibration: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis was performed to compare the influence of different calibrating bougie sizes on clinical outcomes in laparoscopic sleeve gastrectomy (LSG) for patients with obesity. MATERIALS AND METHODS: A systematic review of the literature was performed using the key words: "laparoscopic sleeve gastrectomy", "bougie size", "calibration", "obesity", and "obese" for searches of electronic databases up to October 2017. Clinical characteristics such as, the percentage of excess weight loss (%EWL), overall complications, gastrointestinal leaks, gastroesophageal reflux disease (GERD) were pooled by meta-analysis. Stata 12.0 (Stata Corp, College Station, TX, USA) was used to perform the meta-analysis. RESULTS: Data were extracted from 11 original studies matching our inclusion criteria. In our review, the group of patients who had operations with thinner bougies had a greater %EWL (SMD 0.23, 95% CI 0.14-0.33, P < .001) than the group where larger diameters were used. Furthermore, no significant differences were found in the incidence of overall complications (OR 1.00, 95% CI 0.73-1.37, P = .978), postoperative gastrointestinal leaks (OR 0.91, 95% CI 0.67-1.24, P = .554), and GERD (OR 0.77, 95% CI 0.37-1.59, P = .476) between the two groups. A robust result could not be made about remission of comorbidities using differing diameter bougies due to insufficient data. CONCLUSIONS: Use of thinner diameter bougies in LSG was more effective in enabling weight loss and did not increase the risk of overall complications, gastrointestinal leaks or GERD compared with larger diameter bougies.

Increased ß-Cell Mass in Obese Rats after Gastric Bypass: A Potential Mechanism for Improving Glycemic Control.

BACKGROUND Over the past few decades, bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), has become widely considered the most effective treatment for morbid obesity. In most cases, it results in enhanced glucose management in patients with obesity and type 2 diabetes (T2D), which is observed before significant weight loss. However, what accounts for this effect remains controversial. To gain insight into the benefits of RYGB in T2D, we investigated changes in the ß-cell mass of obese rats following RYGB. MATERIAL AND METHODS RYGB or a sham operation was performed on obese rats that had been fed a high-fat diet (HFD) for 16 weeks. Then, the HFD was continued for 8 weeks in both groups. Additional normal chow diet (NCD) and obese groups were used as controls. RESULTS In the present study, RYGB induced improved glycemic control and enhanced ß-cell function, which was reflected in a better glucose tolerance and a rapidly increased secretion of insulin and C-peptide after glucose administration. Consistently, rats in the RYGB group displayed increased ß-cell mass and islet numbers, which were attributed in part to increased glucagon-like peptide 1 levels following RYGB. CONCLUSIONS Our data indicate that RYGB can improve b-cell function via increasing ß-cell mass, which plays a key role in improved glycemic control after RYGB.

The FOXO1 Gene-Obesity Interaction Increases the Risk of Type 2 Diabetes Mellitus in a Chinese Han Population.

Here, we aimed to study the effect of the forkhead box O1-insulin receptor substrate 2 (FOXO1-IRS2) gene interaction and the FOXO1 and IRS2 genes-environment interaction for the risk of type 2 diabetes mellitus (T2DM) in a Chinese Han population. We genotyped 7 polymorphism sites of FOXO1 gene and IRS2 gene in 780 unrelated Chinese Han people (474 cases of T2DM, 306 cases of healthy control). The risk of T2DM in individuals with AA genotype for rs7986407 and CC genotype for rs4581585 in FOXO1 gene was 2.092 and 2.57 times higher than that with GG genotype (odds ratio [OR] = 2.092; 95% confidence interval [CI] = 1.178-3.731; P = 0.011) and TT genotype (OR = 2.571; 95% CI = 1.404-4.695; P = 0.002), respectively. The risk of T2DM in individuals with GG genotype for Gly1057Asp in IRS2 gene was 1.42 times higher than that with AA genotype (OR = 1.422; 95% CI = 1.037-1.949; P = 0.029). The other 4 single nucleotide polymorphisms (SNPs) had no significant association with T2DM (P > 0.05). Multifactor dimensionality reduction (MDR) analysis showed that the interaction between SNPs rs7986407 and rs4325426 in FOXO1 gene and waist was the best model confirmed by interaction analysis, closely associating with T2DM. There was an increased risk for T2DM in the case of non-obesity with genotype combined AA/CC, AA/AC or AG/AA for rs7986407 and rs4325426, and obesity with genotype AA for rs7986407 or AA for rs4325426 (OR = 3.976; 95% CI = 1.156-13.675; P value from sign test [P(sign)] = 0.025; P value from permutation test [P(perm)] = 0.000-0.001). Together, this study indicates an association of FOXO1 and IRS2 gene polymorphisms with T2DM in Chinese Han population, supporting FOXO1-obesity interaction as a key factor for the risk of T2DM.

Serum LBP Is Associated with Insulin Resistance in Women with PCOS.

INTRODUCTION: Lipopolysaccharide-binding protein (LBP) is closely associated with many metabolic disorders. However, no study has been done to explore the relationship between LBP and polycystic ovary syndrome (PCOS). The objective of this study was to investigate whether the serum LBP level is elevated and associated with insulin resistance (IR) in PCOS. PARTICIPANTS AND DESIGN: In this cross-sectional study, 117 PCOS patients and 121 age-matched controls were recruited. Hyperinsulinemic-euglycemic clamp was performed with an expression of M value for insulin sensitivity. Fasting serum samples were collected to detect LBP, lipids, insulin, sex hormones and high sensitive C reactive protein (hs-CRP). Pearson's correlation and multiple linear regression was used to analyze the associations between M value and LBP level. SETTINGS: The study was performed in a clinical research center. RESULTS: Compared with controls, PCOS subjects had a significantly higher LBP concentration (33.03±14.59 vs. 24.35±10.31 µg/ml, p<0.001), and lower M value (8.21±3.06 vs. 12.31±1.72 mg/min/kg, p<0.001). Both in lean and overweight/obese individuals, serum LBP level was higher in PCOS subjects than that in controls. M value was negatively correlated with body mass index (BMI), fasting serum insulin, triglycerides, low-density lipoprotein cholesterol (LDL-c), free testosterone, high sensitive C reactive protein (hs-CRP) and LBP, whereas positively correlated with high-density lipoprotein cholesterol (HDL-c) and sex hormone binding globulin (SHBG). Serum LBP level was associated with M value after adjusting for BMI, fasting serum insulin, SHBG, as well as hs-CRP. CONCLUSION: Serum LBP level significantly is elevated in PCOS, and is independently associated with IR in PCOS.