Associations of change in body fat percentage with baseline body composition and diabetes remission after bariatric surgery.

OBJECTIVE: The objective of this study was to determine the role of body fat percentage (BFP) changes in diabetes remission (DR) and the association between baseline body composition and its changes after bariatric surgery. METHODS: We analyzed 203 patients with type 2 diabetes who underwent Roux-en-Y gastric bypass. Body composition was measured using a gold-standard-derived predictive equation and magnetic resonance imaging. Body composition changes were calculated as 100 × (baseline value - follow-up value)/baseline value. We verified the results in a laparoscopic sleeve gastrectomy cohort with 311 patients. RESULTS: Compared with non-remission patients in the Roux-en-Y gastric bypass cohort, those who achieved DR showed a higher baseline fat-free mass index (FFMI) and experienced the most significant changes in BFP (p < 0.001). In comparative analyses, BFP changes were significantly better than BMI changes in identifying short- and long-term DR. Linear regression analysis identified FFMI as the most significant baseline variable correlated with BFP changes (p < 0.001). Baseline BMI was positively correlated with changes in BFP but negatively correlated with changes in FFMI. These findings were replicated in the laparoscopic sleeve gastrectomy cohort. CONCLUSIONS: BFP changes determine DR after bariatric surgery, and baseline FFMI is crucial for BFP changes. A low initial BMI is associated with a smaller BFP reduction and greater FFMI loss after bariatric surgery.

Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders.

Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders. These people store fat in subcutaneous adipose tissue (SAT) rather than in visceral adipose tissue (VAT). However, the molecules participating in this specific scenario remain elusive. Rab18, a lipid droplet (LD)-associated protein, mediates the contact between the endoplasmic reticulum (ER) and LDs to facilitate LD growth and maturation. In the present study, we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice. Rab18 adipocyte-specific knockout (Rab18 AKO) mice had a decreased volume ratio of SAT to VAT compared with wildtype mice. When subjected to high-fat diet (HFD), Rab18 AKO mice had increased ER stress and inflammation, reduced adiponectin, and decreased triacylglycerol (TAG) accumulation in SAT. In contrast, TAG accumulation in VAT, brown adipose tissue (BAT) or liver of Rab18 AKO mice had a moderate increase without ER stress stimulation. Rab18 AKO mice developed insulin resistance and systematic inflammation. Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT, similar to the counterpart mice. Furthermore, Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress, indicating the involvement of Rab18 in alleviating lipid toxicity. Rab18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT. In conclusion, our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

Nomogram for Predicting Remission of Metabolic Syndrome 1 Year after Sleeve Gastrectomy Surgery in Chinese Patients with Obesity.

PURPOSE: Sleeve gastrectomy (SG) is a widely used and effective treatment for patients with obesity and comorbid metabolic abnormalities. No specialized tool is available to predict metabolic syndrome (MS) remission after SG. We presented a nomogram that evaluated the probability of MS remission in obese patients 1 year after SG. MATERIALS AND METHODS: Patients with preoperative MS who underwent SG were enrolled in this retrospective study. They were divided into a training set and a validation set. Multivariate logistic regression analysis was performed to identify independent predictors of MS remission, and these predictors were included in the nomogram. Receiver operating characteristic curve was used to evaluate discrimination. Calibration was performed with the Hosmer-Lemeshow goodness-of-fit test. The net benefits of the nomogram were evaluated using decision curve analysis (DCA). RESULTS: Three hundred and eighteen patients with a median age of 34.0 years were analyzed. A training set and a validation set with 159 individuals each were established. A combination of age, preoperative high-density lipoprotein cholesterol, elevated triglycerides and glycated hemoglobin level independently and accurately predicted MS remission. The nomogram included these factors. The discriminative ability was moderate in training and validation sets (Area under curve 0.800 and 0.727, respectively). The Hosmer-Lemeshow X2 value of the nomogram was 8.477 (P = 0.388) for the training set and 5.361 (P = 0.718) for the validation set, indicating good calibration. DCA showed the nomogram had clinical benefits in both datasets. CONCLUSION: Our nomogram could accurately predict MS remission in Chinese patients with obesity 1 year after SG.

Resistant starch intake facilitates weight loss in humans by reshaping the gut microbiota.

Emerging evidence suggests that modulation of gut microbiota by dietary fibre may offer solutions for metabolic disorders. In a randomized placebo-controlled crossover design trial (ChiCTR-TTRCC-13003333) in 37 participants with overweight or obesity, we test whether resistant starch (RS) as a dietary supplement influences obesity-related outcomes. Here, we show that RS supplementation for 8 weeks can help to achieve weight loss (mean -2.8 kg) and improve insulin resistance in individuals with excess body weight. The benefits of RS are associated with changes in gut microbiota composition. Supplementation with Bifidobacterium adolescentis, a species that is markedly associated with the alleviation of obesity in the study participants, protects male mice from diet-induced obesity. Mechanistically, the RS-induced changes in the gut microbiota alter the bile acid profile, reduce inflammation by restoring the intestinal barrier and inhibit lipid absorption. We demonstrate that RS can facilitate weight loss at least partially through B. adolescentis and that the gut microbiota is essential for the action of RS.

Adipocyte-Specific Hnrnpa1 Knockout Aggravates Obesity-Induced Metabolic Dysfunction via Upregulation of CCL2.

Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) is involved in lipid and glucose metabolism via mRNA processing. However, whether and how HNRNPA1 alters adipocyte function in obesity remain obscure. Here, we found that the obese state downregulated HNRNPA1 expression in white adipose tissue (WAT). The depletion of adipocyte HNRNPA1 promoted markedly increased macrophage infiltration and expression of proinflammatory and fibrosis genes in WAT of obese mice, eventually leading to exacerbated insulin sensitivity, glucose tolerance, and hepatic steatosis. Mechanistically, HNRNPA1 interacted with Ccl2 and regulated its mRNA stability. Intraperitoneal injection of CCL2-CCR2 signaling antagonist improved adipose tissue inflammation and systemic glucose homeostasis. Furthermore, HNRNPA1 expression in human WAT was negatively correlated with BMI, fat percentage, and subcutaneous fat area. Among individuals with 1-year metabolic surgery follow-up, HNRNPA1 expression was positively related to percentage of total weight loss. These findings identify adipocyte HNRNPA1 as a link between adipose tissue inflammation and systemic metabolic homeostasis, which might be a promising therapeutic target for obesity-related disorders.

Associations of Serum Uric Acid to High-Density Lipoprotein Cholesterol Ratio with Trunk Fat Mass and Visceral Fat Accumulation.

Background: It has been reported recently that the ratio of uric acid to high-density lipoprotein cholesterol (UHR) is correlated with several metabolic disorders. The present study aimed to investigate the associations of UHR with body fat content and distribution. Methods: This study enrolled 300 participants (58 men and 242 women) aged 18 to 65 years. The levels of serum uric acid and high-density lipoprotein cholesterol were measured by standard enzymatic methods. The overall fat content and segmental fat distribution were assessed with an automatic bioelectrical impedance analyzer. In the population with obesity, the visceral fat area (VFA) and subcutaneous fat area (SFA) were measured using magnetic resonance imaging. Results: Among the study population, 219 individuals (73.0%) were with obesity. The median level of UHR in individuals with obesity was 33.7% (26.2% - 45.9%), which was significantly higher than that in those without obesity [22.6% (17.0% - 34.4%), P < 0.01]. UHR was positively associated with overall fat content and segmental fat distribution parameters (all P < 0.01). In multivariate linear regression analysis, compared with body mass index, waist circumference was more closely associated with UHR (standardized ß = 0.427, P < 0.001) after adjusting for confounding factors. Additionally, total fat mass (standardized ß = 0.225, P = 0.002) and trunk fat mass (standardized ß = 0.296, P = 0.036) were more closely linked to UHR than total fat-free mass and leg fat mass, respectively. In the population with obesity, VFA was independently correlated with UHR (P < 0.01), while SFA was not associated with UHR. Conclusion: UHR was significantly associated with overall fat content and trunk fat accumulation. In the population with obesity, UHR was positively associated with VFA. Attention should be paid to the role of excessive trunk fat mass in the relationship between UHR and metabolic disorders.

The impact of metabolic surgery on natural conception rates in women with infertility, obesity and polycystic ovary syndrome: a retrospective study.

BACKGROUND: Women with obesity and polycystic ovary syndrome (OPOS) are at high risk for infertility. However, the reproductive effects of metabolic surgery on women with infertility and OPOS have not been fully elucidated. OBJECTIVES: We investigated the natural conception rates after metabolic surgery, and the variables associated with infertility in women with OPOS. SETTING: Shanghai Sixth People's Hospital, Shanghai, China. METHODS: This study included 72 women with infertility and OPOS who underwent metabolic surgery and were followed up for 4 years after surgery. Finally, 54 patients completed the study. Reproductive outcomes were assessed, along with changes in anthropometric parameters and metabolic indices before and 1 year after surgery (prepregnancy). Logistic regression analysis was used to identify variables influencing natural conception and delivery outcomes. RESULTS: After metabolic surgery, 35 patients (64.8%) became pregnant naturally, while 16 were still unable to conceive naturally. Preoperative body mass index (BMI) tended to be lower in the natural conception group than in the no natural conception group (38.9 ± 6.9 versus 43.6 ± 11.0 kg/m2, P = .070) and there were no significant differences in weight loss between the 2 groups after surgery. Logistic regression analysis showed that the BMI 1 year after surgery (prepregnancy) was an independent predictor of natural conception, and receiver operating characteristic analysis showed that a BMI of 27.0 kg/m2 was the optimal cutoff for predicting successful natural conception after surgery. CONCLUSIONS: Metabolic surgery can improve fertility in women with OPOS. Patients with a BMI < 27.0 kg/m2 1 year after surgery (prepregnancy) are more likely to become pregnant naturally and give birth.

Neck circumference as a potential indicator of pre-sarcopenic obesity in a cohort of community-based individuals.

BACKGROUND & AIMS: ESPEN/EASO advocates screening for sarcopenic obesity based on the concomitant presence of an elevated body mass index (BMI) or waist circumference. Neck circumference (NC) is another simple and reliable anthropometric measurement for estimating obesity; however, its ability to detect sarcopenic obesity has not yet been established. The aim of the present study was to explore the association between NC and sarcopenic obesity in a Shanghai community population. METHODS: The study included 1542 participants (622 men and 920 women) with a mean age of 58 years who underwent an examination for the detection of obesity at baseline in 2013-2014 and received a re-examination in 2015-2016. An automatic bioelectric impedance analyzer was used to estimate body composition, and magnetic resonance imaging was used to measure abdominal fat distribution. The definition of pre-sarcopenic obesity combined low skeletal muscle mass adjusted by weight (SMM/W) with obesity which defined according to overall adiposity or fat distribution as BMI ≥25 kg/m2, fat percentage (fat%) ≥ 25% in men and 30% in women, or visceral fat area (VFA) ≥ 80 cm2, respectively. RESULTS: In both men and women, subjects with low SMM/W had a higher level of NC than those without (both P < 0.01). In turn, participants with elevated NC had a higher proportion of pre-sarcopenic obesity in both men and women, regardless of adiposity status assessed by BMI, fat%, or VFA (all P < 0.01). During an average follow up of 2.1 years, for each 1 cm increase in NC, multivariable-adjusted hazard ratios of pre-sarcopenic obesity in which adiposity status assessed by high BMI were 1.40 (1.11-1.76) in men and 1.32 (1.13-1.56) in women; in addition, such association remained between NC and pre-sarcopenic obesity assessed by high fat% or high VFA. CONCLUSION: NC is closely associated with the incidence of sarcopenic obesity, suggesting that it could be helpful for screening sarcopenic obesity in a community-based population.

Sex- and age-specific associations between abdominal fat and non-alcoholic fatty liver disease: a prospective cohort study.

Obesity is closely related to non-alcoholic fatty liver disease (NAFLD). Although sex differences in body fat distribution have been well demonstrated, little is known about the sex-specific associations between adipose tissue and the development of NAFLD. Using community-based cohort data, we evaluated the associations between magnetic resonance imaging-quantified areas of abdominal adipose tissue, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and incident NAFLD in 2830 participants (1205 males and 1625 females) aged 55-70 years. During a 4.6-year median follow-up, the cumulative incidence rates of NAFLD increased with areas of VAT and SAT both in males and females. Further analyses showed that the abovementioned positive associations were stronger in males than in females, especially in participants under 60 years old. In contrast, these sex differences disappeared in those over 60 years old. Furthermore, the risk of developing NAFLD increased nonlinearly with increasing fat area in a sex-specific pattern. Additionally, sex-specific potential mediators, such as insulin resistance, lipid metabolism, inflammation, and adipokines, may exist in the associations between adipose tissue and NAFLD. This study showed that the associations between abdominal fat and the risk of NAFLD were stratified by sex and age, highlighting the potential need for sex- and age-specific management of NAFLD.

Incidence rate and risk factors for hypoglycemia among individuals with type 1 diabetes or type 2 diabetes in China receiving insulin treatment.

AIMS: We investigated the real-world incidence of hypoglycemic events among patients with type 1 or type 2 diabetes (T1DM or T2DM) receiving insulin in routine clinical practice in China. METHODS: In this observational study, data were collected electronically via the Lilly Connected Care Program (LCCP) electronic system from adults with T1DM or T2DM who had registered on LCCP between 1 February 2019 and 31 January 2022, had used insulin for a full 12-week period following registration. The following outcomes were assessed during the 12 weeks following registration: incidence of level 1 and level 2 hypoglycemia. RESULTS: In total, 22,752 patients were enrolled. Among patients with monitoring data, over the 12-week study period, level 1 and 2 hypoglycemia were experienced by 48.8% and 25.9% of patients with T1DM and 26.5% and 13.9% of patients with T2DM. The proportion of patients treated with oral anti-diabetes drugs (OADs) capable of producing hypoglycemia (sulfonylurea or glinide) was 1.3% in T1DM and 1.6% in T2DM, respectively. Questionnaire data revealed that up to 92.5% of hypoglycemic events occurred outside of hospital and 18.6% were serious. CONCLUSIONS: These real-world data collected from Chinese patients with diabetes receiving insulin treatment reveal a relatively high percentage of patients experiencing hypoglycemia, with around one quarter of these events classified as severe and as many as 92.5% occurring outside of a hospital or clinic.

Interaction between serum neutrophil gelatinase associated lipocalin and visceral fat area on cardiovascular health in a cohort of community-based individuals.

BACKGROUND: We assessed the predictive values of neutrophil gelatinase-associated lipocalin (NGAL), fat distribution, and their interaction on the development of major adverse cardiovascular events (MACE) in a community-based cohort of middle-aged and older individuals. METHODS: This prospective study involved 1349 adults (43.2% men) aged 50-80 y, without baseline cardiovascular diseases, from communities in 2013-2014. All participants were followed up for a mean of 7.6 y via phone calls and medical records. Serum NGAL concentrations were analyzed at baseline. Fat distribution, including subcutaneous fat area and visceral fat area (VFA), was assessed by magnetic resonance imaging. RESULTS: In fully-adjusted Cox regression models, baseline high NGAL concentrations were related to an increased risk of MACE in women [HR 1.75, 95% CI 1.03-2.99], compared with low NGAL concentrations. After stratification by VFA concentrations, the observed association was more predominant in women with baseline low VFA (HR 1.24, 95% CI 1.11-1.38). Moreover, the association between NGAL and MACE was interacted by VFA, strengthening the association at low VFA concentrations (Pinteraction < 0.05). CONCLUSIONS: Serum NGAL determined at baseline predicts the development of MACE, and the association is modified by VFA in women.

Effect of regional body composition changes on bone density remodeling after sleeve gastrectomy.

Background: Sleeve gastrectomy (SG) results in bone mineral density (BMD) loss and varying body composition parameters. However, the effects of body compositions on bone health are controversial. In order to accurately demonstrate their relationship and provide new insights into the causes of BMD loss after sleeve gastrectomy, this study is aimed to investigate the role of changes in body composition in BMD loss 12 months after SG. Methods: 41 Chinese individuals with obesity (25 women and 16 men) who underwent SG were prospectively examined for at least 12 months. Measurements of anthropometrics, body composition, BMD and blood samples were collected. Results: For 12 months, the femoral neck (FN) BMD and total hip (TH) BMD decreased significantly compared with baseline in both sexes but not lumbar spine (LS) BMD. Greater TH BMD loss was observed in men than in women. For the first 6 months post-SG, the FN BMD loss was positively associated with the estimated fat free mass index (eFFMI) reduction in women (adjusted ß = 0.77, P = 0.004) and positively associated with reduction of subcutaneous fat area (SFA) in men (r = 0.931, P = 0.007). For 12 months post-SG, the FN BMD loss was negatively associated with visceral fat area (VFA) reduction in women (adjusted ß = -0.58, P = 0.027) and men (adjusted ß = -0.68, P = 0.032). TH BMD loss was positively associated with waist circumference reduction in women (r = 0.448, P = 0.028). Conclusion: FN and TH BMD decrease after SG in both women and men. The changes in body compositions are associated with BMD loss at different time points and bone sites. Our data emphasize the limitation of simply taking the total weight loss (% TWL) as an influencing factor of bone mineral density and the necessity of delineating body composition in relevant studies.

Changes of health-related quality of life after initiating basal insulin treatment among people with type 2 diabetes.

To assess the association between insulin regimens and health-related quality of life (HRQoL) after the introduction of basal insulin (BI) among people with type 2 diabetes in real-world clinical settings. 16,339 registered people with diabetes who had inadequate glycaemic control by oral agents initiated BI (either single BI or Basal-bolus) and completed a 6-month follow-up from 209 hospitals were included in the analyses. At the end of the follow-up, the switches of insulin regimens, change of HRQoL (EQ-5D-3L) and their associations were assessed. Initial insulin regimens of single BI and of basal-bolus (BI included Glargine, Detemir, and Neutral Protamine Hagedorn) accounted for 75.6% and 24.4%, respectively. At 6 months, regimens used were BI alone (65.2%), basal-bolus (10.4%), and premixed (6.4%), whereas 17.9% stopped all insulin therapy. The visual analogue scale score increased by 5.46 (P < .001), and the index value increased slightly by 0.02 (P < .001). Univariate analysis showed that people with diabetes taking basal-bolus regimen had the greatest improvement on HRQoL in all dimensions, especially in the reduction of the percentage of Pain/Discomfort (by 10.03%) and Anxiety/Depression (by 11.21%). In multivariable analysis, single BI or premixed insulin at 6 months was associated with more improvement of visual analogue scale score compared with stopping all insulin. Improved HRQoL was observed after initiating BI in people with type 2 diabetes . If the same achievement on HbA1c control can be guaranteed, single BI is preferred to other regimens from the viewpoint of HRQoL. Basal-bolus has the most significant potential to increase HRQoL, however, the people with diabetes characteristics differ from those initiating BI alone. Further longitudinal cohort study with a longer study period might be necessary to evaluate the certain effect.

Interaction between haptoglobin genotype and glycemic variability on diabetic macroangiopathy: a population-based cross-sectional study.

PURPOSE: Haptoglobin (Hp) is a hemoglobin-binding protein that functions as an antioxidant in human plasma. It is reported that glycemic variability (GV) plays a key role in diabetes-related complications associated with impaired glucose metabolism and oxidative stress. Here we aim to investigate whether the effect of GV on diabetic macroangiopathy depends on Hp genotype in type 2 diabetes. METHODS: A number of 860 Chinese patients with type 2 diabetes was genotyped and assigned to two Hp subgroups (Hp 2-2 and Hp 1 carriers). Glycemic variability (GV) was assessed by using a retrospective continuous glucose monitoring system for three consecutive days, and it was measured using the glucose coefficient of variation (%CV), which is calculated as the ratio of glucose standard deviation to glucose mean. Clinical features, history of cardiac surgery, and vascular imaging tests were utilized to diagnose macroangiopathy. We evaluated the interaction between Hp genotypes and %CV on diabetic macroangiopathy. Furthermore, serum concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured using an enzyme-linked immunosorbent assay as a biomarker of oxidative stress. RESULTS: Serum 8-OHdG levels were positively correlated with %CV in Hp 1 carriers (r = 0.117; p = 0.021). Patients in the highest %CV tertile were associated with a higher prevalence of diabetic macroangiopathy than those in the lowest %CV tertile in Hp 1 carriers (OR = 2.461 [95% CI, 1.183-5.121], p = 0.016), but not in those with Hp 2-2 genotype (OR = 0.540 [95% CI, 0.245-1.191], p = 0.127). A significant interactive effect of Hp genotypes and %CV on diabetic macroangiopathy was found (p interaction = 0.008). CONCLUSION: Hp genotype modifies the effect of GV on diabetic macroangiopathy among Chinese patients with type 2 diabetes.

Insight to the association among fibroblast growth factor 21, non-alcoholic fatty liver disease and cardiovascular outcomes: A population-based study.

OBJECTIVE: We aimed to investigate whether there was a joint effect of fibroblast growth factor 21 (FGF21) and non-alcoholic fatty liver disease (NAFLD) or interaction on the incidence of cardiovascular diseases based on a community-dwelling population. METHODS: Serum FGF21 levels were determined using an enzyme-linked immunosorbent method. NAFLD was diagnosed via ultrasonography. Multivariable-adjusted cox proportional hazards models were used to assess the joint effects of FGF21 and NAFLD on the major adverse cardiovascular events (MACE). RESULTS: A total of 1194 participants were enrolled in the final analysis. The multivariable-adjusted hazard ratio (HR) of MACE was 1.84 (95% confidence interval (CI) 1.18-2.86) in participants with diagnosed NAFLD at baseline, compared with those without NAFLD at baseline. The multivariable-adjusted HRs of MACE across quintiles of serum FGF21 levels at baseline were 1.00, 1.48 (95%CI 0.68-3.21), 2.01 (95%CI 0.98-4.13), 1.94 (95%CI 0.94-4.02) and 2.14 (95%CI 1.03-4.44) respectively. Participants with high FGF21 levels and NAFLD at baseline showed the highest risk of MACE with a significant interaction between the presence of NAFLD and serum FGF21 levels. CONCLUSIONS: Both FGF21 and NAFLD were associated with MACE, while the association between FGF21 and MACE may be interacted by the presence of NAFLD at baseline.

Machine Learning Prediction of Iron Deficiency Anemia in Chinese Premenopausal Women 12 Months after Sleeve Gastrectomy.

Premenopausal women, who account for more than half of patients for bariatric surgery, are at higher risk of developing postoperative iron deficiency anemia (IDA) than postmenopausal women and men. We aimed at establishing a machine learning model to evaluate the risk of newly onset IDA in premenopausal women 12 months after sleeve gastrectomy (SG). Premenopausal women with complete clinical records and undergoing SG were enrolled in this retrospective study. Newly onset IDA after surgery, the main outcome, was defined according to the age- and gender-specific World Health Organization criteria. A linear support vector machine model was developed to predict the risk of IDA after SG with the top five important features identified during feature selection. Four hundred and seven subjects aged 31.0 (Interquartile range (IQR): 26.0-36.0) years with a median follow-up period of 12 (IQR 7-13) months were analyzed. They were divided into a training set and a validation set with 285 and 122 individuals, respectively. Preoperative ferritin, age, hemoglobin, creatinine, and fasting C-peptide were included. The model showed moderate discrimination in both sets (area under curve 0.858 and 0.799, respectively, p < 0.001). The calibration curve indicated acceptable consistency between observed and predicted results in both sets. Moreover, decision curve analysis showed substantial clinical benefits of the model in both sets. Our machine learning model could accurately predict newly onset IDA in Chinese premenopausal women with obesity 12 months after SG. External validation was required before the model was used in clinical practice.

Clusterin is closely associated with adipose tissue insulin resistance.

AIMS: Clusterin (encoded by CLU) is a novel adipokine. Serum clusterin levels were elevated in populations with obesity and diabetes. Adipose tissue insulin resistance (Adipo-IR) is proposed as an early metabolic defect that precedes systemic insulin resistance. Herein, we aimed to investigate the relationship between serum clusterin levels and Adipo-IR. CLU expression in human abdominal adipose tissues and clusterin secretion in human adipocytes was also explored. MATERIALS AND METHODS: A total of 201 participants (aged 18-62 years, 139 of whom were obese) were recruited. Enzyme-linked immunosorbent assay was used to measure serum clusterin levels. Adipo-IR was calculated from the product of fasting free fatty acids and fasting insulin levels. Transcriptome sequencing of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) was performed. Human adipocytes were used to detect the secretion of clusterin. RESULTS: Serum clusterin levels were independently associated with Adipo-IR after adjusting for several confounding factors (standardised ß = 0.165, p = 0.021). CLU expression in VAT and SAT was associated with obesity-related metabolic risk factors. Higher CLU expression in VAT was accompanied by an increase in collagen accumulation. Clusterin secretion in differentiated human adipocytes was stimulated by insulin and inhibited by rosiglitazone. CONCLUSIONS: Clusterin is strongly associated with Adipo-IR. Serum clusterin may function as an effective indicator of adipose tissue insulin resistance.

Targeted gene panel provides advantages over whole-exome sequencing for diagnosing obesity and diabetes mellitus.

A small fraction of patients diagnosed with obesity or diabetes mellitus has an underlying monogenic cause. Here, we constructed a targeted gene panel consisting of 83 genes reported to be causative for monogenic obesity or diabetes. We performed this panel in 481 patients to detect causative variants and compared these results with whole-exome sequencing (WES) data available for 146 of these patients. The coverage of targeted gene panel sequencing was significantly higher than that of WES. The diagnostic yield in patients sequenced by the panel was 32.9% with subsequent WES leading to three additional diagnoses with two novel genes. In total, 178 variants in 83 genes were detected in 146 patients by targeted sequencing. Three of the 178 variants were missed by WES, although the WES-only approach had a similar diagnostic yield. For the 335 samples only receiving targeted sequencing, the diagnostic yield was 32.2%. In conclusion, taking into account the lower costs, shorter turnaround time, and higher quality of data, targeted sequencing is a more effective screening method for monogenic obesity and diabetes compared to WES. Therefore, this approach could be routinely established and used as a first-tier test in clinical practice for specific patients.

Low total osteocalcin levels are associated with the risk of cardiovascular events among women with hyperglycaemia: a 7.6-year prospective study.

PURPOSE: To investigate the association between circulating osteocalcin and incident cardiovascular diseases in a community-based cohort, and further assess whether the association differs by different glycemic stages. METHODS: This cohort study included 1428 participants (626 men and 802 women) aged 50-80 years, without baseline cardiovascular diseases, and with osteocalcin data available. Circulating total osteocalcin levels were measured by electrochemiluminescence immunoassay. Multivariate Cox proportional hazards models were used to assess the relationship between osteocalcin levels and different glycemic stages with cardiovascular events. RESULTS: At baseline, 437 participants were normoglycaemia and 991 participants were hyperglycaemia. Median circulating osteocalcin levels were 16.43 (13.34-20.19) and 21.66 (17.95-26.11) ng/mL in men and women, respectively. During a mean follow-up of 7.6 years, 144 cases of cardiovascular diseases occurred (10.1%). The risk of incident cardiovascular diseases linearly increased with a decrease in baseline osteocalcin quartiles (quartile 1 versus quartile 4: hazard ratio 2.44, 95% confidence interval 1.07-5.55) in women, while not in men (Pinteraction on sex = 0.028). Subgroup analyses showed that the association was more predominant in participants with baseline hyperglycaemia. Besides, the joint effect of baseline decreased osteocalcin levels and hyperglycaemia resulted in higher risks of future cardiovascular diseases. CONCLUSIONS: Low baseline osteocalcin levels were associated with high risks of cardiovascular diseases in middle-aged and elderly women, which were more predominant among those with baseline hyperglycaemia.