The relationship between serum superoxide dismutase and thyroid function in obese patients after Laparoscopic sleeve gastrectomy.

To investigate the cross-sectional and longitudinal correlation between serum superoxide dismutase (SOD) levels and thyroid function with obesity before and after laparoscopic sleeve gastrectomy (LSG). Patients with morbid obesity (n = 219, 112 males and 107 females) who underwent LSG were selected and they were subdivided into normal levels of SOD (NSOD, n = 112) and high levels of SOD (HSOD, n = 107) according to the median value of SOD levels (183 U/mL). SOD and thyroid hormones were measured and compared at baseline, 3, 6, and 12 months after LSG. The HSOD group had lower body mass index (BMI), total thyroxine (TT4), and thyroid-stimulating hormone (TSH) than the NSOD group (p < 0.001, p = 0.031, p < 0.001, respectively). However, they had higher free triiodothyronine (FT3) and free thyroxine (FT4) (p = 0.019 and p = 0.017, respectively). SOD was significantly negatively associated with TSH and positively associated with FT4. Of all the patients, 22.31% (NSOD: 66.67%; HSOD: 33.33%) had subclinical hypothyroidism (SH), and there were lower SOD levels in the SH group. Preoperative SOD was a protective factor for SH. After LSG, SOD and FT4 levels were increased at 12 months after LSG, however, TSH, FT3, total triiodothyronine (TT3) and TT4 levels decreased compared to the preoperative levels at 3, 6, and 12 months in the SH group. Postoperative changes in FT4 and TT4 levels correlated with changes in SOD levels. SOD, which is correlated with thyroid hormones, protects against SH in patients with obesity. The improvement in thyroid function with SH after LSG may be related to increased SOD levels.

Derlin-1 ameliorates nonalcoholic hepatic steatosis by promoting ubiquitylation and degradation of FABP1.

BACKGROUND AND AIMS: The functions of liver fatty acid binding protein 1 (FABP1) in the regulation of nonalcoholic fatty liver disease (NAFLD) have been previously established. However, how FABP1 expression is dynamically regulated in metabolic disorders is unclear. Previous studies have reported that ubiquitin proteasome-mediated degradation of FABP1 is involved, but the mechanism remains unknown. METHODS: Dysregulated expression of hepatic FABP1 and Derlin-1 was observed in NAFLD patients. We performed mice hepatic tissue coimmunoprecipitation based mass spectrum assays. Interaction between Derlin-1 and FABP1, and its impact on FABP1 ubiquitination status was evaluated by coimmunoprecipitation. The role of Derlin-1 in lipid deposition was tested using adenovirus-mediated overexpression in C57BL/6 mice, as well as by Derlin-1 overexpression or knockdown in HepG2 cells. RESULTS: As a subunit of the endoplasmic reticulum-associated degradation complex, Derlin-1 was negatively associated with NAFLD patients, interacted with and ubiquitinated FABP1. Derlin-1 suppressed FABP1 levels and inhibited lipid deposition through a FABP1-dependent pathway. Additionally, Trim25, an E3 ubiquitin ligase present in the endoplasmic reticulum, was recruited to promote Derlin-1-related polyubiquitylation of FABP1, thereby creating a ubiquitin-associated network for FABP1 regulation. Derlin-1 overexpression ameliorated hepatic steatosis in both C57BL/6 mice and HepG2 cells, and contributed to attenuated weight gain, lower liver weight, and visceral fat mass. CONCLUSIONS: FABP1 was degraded by Derlin-1 through ubiquitin modification. Negative regulation of FABP1 by Derlin-1 overexpression, suppressed lipid metabolism and alleviated lipid deposition in vivo and in vitro. Hence, Derlin-1 activation in hepatocytes may represent a potential therapeutic strategy for NAFLD.

Improved Insulin Secretion Response and Beta-cell Function Correlated with Increased Prolactin Levels After Laparoscopic Sleeve Gastrectomy in Morbidly Obese Patients with Acanthosis Nigricans.

OBJECTIVE: To explore insulin secretion patterns, ß-cell function, and serum prolactin (PRL) concentrations in Chinese morbidly obese patients with Acanthosis nigricans (AN) and their alterations after laparoscopic sleeve gastrectomy (LSG). METHODS: A total of 138 morbidly obese subjects undergoing LSG were categorized as simple obesity without AN (OB group, n = 55) and obesity with AN (AN group, n = 83). Oral glucose tolerance test (OGTT), PRL, and related metabolic indices were performed pre- and 12 months post-LSG. Insulin secretion patterns were derived from insulin secretion peak time during OGTT: type I (peak at 30 or 60 min) and type II (peak at 120 or 180 min). RESULTS: Preoperatively, AN group showed significantly higher proportions of type II insulin secretion pattern, fasting insulin (FINS), and homeostatic model assessment of insulin resistance (HOMA-IR) whereas lower oral glucose insulin sensitivity (OGIS), insulinogenic index (IGI), and disposition index (DI) than OB group, which were improved significantly at 12 months postoperatively in both groups, more pronounced in AN group. Intriguingly, serum PRL declined substantially in AN group than OB group at baseline whereas elevated only in the AN group post-LSG. After adjusting for confounding factors, elevated PRL correlated significantly with increased IGI and DI, and decreased HOMA-IR in both genders, as well as increased OGIS in females, which was detected only in the AN group CONCLUSION: Morbidly obese patients with AN presented delayed insulin secretion response, impaired insulin secretion, and ß-cell dysfunction, which were significantly improved by LSG and might benefit from elevated PRL.

Association between liver-type fatty acid-binding protein and hyperuricemia before and after laparoscopic sleeve gastrectomy.

Background: Liver-type fatty acid-binding protein (FABP1) contributes to metabolic disorders. However, the relationship between FABP1 and hyperuricemia remains unknown. We aimed to evaluate the correlation between serum FABP1 and hyperuricemia in patients with obesity before and after laparoscopic sleeve gastrectomy (LSG). Methods: We enrolled 105 patients (47 men and 58 women) with obesity who underwent LSG. They were divided into two groups: normal levels of uric acid (UA) (NUA, n = 44) and high levels of UA (HUA, n = 61) with matching sexes. FABP1 levels and other biochemical parameters were measured at baseline and 3, 6, and 12 months after LSG. Results: Serum FABP1 levels were significantly higher in the HUA group than in the NUA group (34.76 ± 22.69 ng/mL vs. 25.21 ± 21.68 ng/mL, P=0.024). FABP1 was positively correlated with UA (r=0.390, P=0.002) in the HUA group. The correlation still existed after adjusting for confounding factors. Preoperative FABP1 levels were risk factors for hyperuricemia at baseline. UA and FABP1 levels decreased at 3, 6, and 12 months postoperatively. FABP1 showed a more significant decrease in the HUA group than in the NUA group at 12 months (27.06 ± 10.98 ng/mL vs. 9.54 ± 6.52 ng/mL, P=0.003). Additionally, the change in FABP1 levels positively correlated with changes in UA levels in the HUA group 12 months postoperatively (r=0.512, P=0.011). Conclusions: FABP1 was positively associated with UA and may be a risk factor for hyperuricemia in obesity. FABP1 levels were higher but decreased more after LSG in obese patients with hyperuricemia than in those without hyperuricemia.

Myeloid FoxO1 depletion attenuates hepatic inflammation and prevents nonalcoholic steatohepatitis.

Hepatic inflammation is culpable for the evolution of asymptomatic steatosis to nonalcoholic steatohepatitis (NASH). Hepatic inflammation results from abnormal macrophage activation. We found that FoxO1 links overnutrition to hepatic inflammation by regulating macrophage polarization and activation. FoxO1 was upregulated in hepatic macrophages, correlating with hepatic inflammation, steatosis, and fibrosis in mice and patients with NASH. Myeloid cell conditional FoxO1 knockout skewed macrophage polarization from proinflammatory M1 to the antiinflammatory M2 phenotype, accompanied by a reduction in macrophage infiltration in liver. These effects mitigated overnutrition-induced hepatic inflammation and insulin resistance, contributing to improved hepatic metabolism and increased energy expenditure in myeloid cell FoxO1-knockout mice on a high-fat diet. When fed a NASH-inducing diet, myeloid cell FoxO1-knockout mice were protected from developing NASH, culminating in a reduction in hepatic inflammation, steatosis, and fibrosis. Mechanistically, FoxO1 counteracts Stat6 to skew macrophage polarization from M2 toward the M1 signature to perpetuate hepatic inflammation in NASH. FoxO1 appears to be a pivotal mediator of macrophage activation in response to overnutrition and a therapeutic target for ameliorating hepatic inflammation to stem the disease progression from benign steatosis to NASH.

High-Sensitive CRP Correlates With the Severity of Liver Steatosis and Fibrosis in Obese Patients With Metabolic Dysfunction Associated Fatty Liver Disease.

Background: Metabolic dysfunction associated fatty liver disease (MAFLD) is the most common hepatopathy worldwide due to the obesity epidemic and is associated with chronic low-grade inflammation. High-sensitive C-reactive protein (hsCRP) as an inflammatory marker has been used in diagnosing MAFLD. However, the association between hsCRP and the severity of liver steatosis and fibrosis among obese patients with MAFLD remains to be elucidated. Objective: To explore the correlation of hsCRP with the severity of liver steatosis and fibrosis among Chinese obese patients with MAFLD. Methods: A total of 393 obese patients with mean BMI 34.8 ± 6.6 kg/m2 were selected and categorized as MAFLD and non-MAFLD groups. Anthropometric data, biochemical indices, and hsCRP were measured. The severity of hepatic steatosis and fibrosis was assessed using FibroScan. Multivariate logistic regression analysis was performed to determine the relationship between hsCRP and the risk of MAFLD and its disease severity. Results: Patients with MAFLD showed significantly elevated hsCRP levels and were more likely to have severe steatosis and fibrosis compared to those without MAFLD. The proportions of MAFLD, severe steatosis, and severe fibrosis were significantly increased across the hsCRP quartiles (P-trend = 0.004, 0.021, and 0.006, respectively). After multivariable adjustments, the adjusted ORs (AORs) and 95%CI for MAFLD were 1.00 (reference), 1.298 (0.587-2.872), 2.407 (1.002-5.781), and 2.637(1.073-6.482) (Q1-Q4, P-trend = 0.014). Likewise, the AORs (95%CI) for severe steatosis and severe fibrosis were remarkably increased with the increment of serum hsCRP quartiles (P-trend < 0.001, P-trend = 0.021, respectively). Conclusions: Elevated serum hsCRP levels were associated with increased risk of MAFLD among Chinese obese patients and correlated positively with the severity of liver steatosis and fibrosis, suggesting that hsCRP can be used as a potential biomarker to monitor and predict disease severity among Chinese obese population with MAFLD.

Association between Depression and Clinical Outcomes following Percutaneous Coronary Intervention: A Meta-Analysis.

BACKGROUND: Several studies suggested that depression was associated with poor prognosis following percutaneous coronary intervention (PCI) in coronary heart disease (CHD), whereas other studies showed that there were no associations between depression and poor outcomes. OBJECTIVES: Considering these problems, this meta-analysis was conducted to evaluate the relationship between depression and clinical outcomes after PCI. METHODS: Articles published before July 2021 were analyzed from the databases: PubMed, Web of Science, EMBASE, Medline, and Google Scholar. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed to generate a pooled effect size and 95% CI with a random or fixed effects model. Q test and I2 were used to assess heterogeneities between studies. RESULTS: The meta-analysis indicated that depression was associated with a higher risk of major adverse cardiac events (MACE) after PCI with a random effects model (HR = 1.89, 95% CI: 1.33-2.68, I2 = 57.0%, p = 0.023). The study indicated that depression was associated with a higher risk of all-cause mortality after PCI with a fixed effects model (HR = 1.71, 95% CI: 1.43-2.05, I2 = 0.0%, p = 0.756). The study indicated no significant association between depression and risk of repeat revascularization after PCI with a random effects model (HR = 2.10, 95% CI: 0.96-4.58, I2 = 68.9%, p = 0.022). CONCLUSION: Results indicated that depression is associated with adverse clinical outcomes in CHD patients' post-PCI. Appropriate mental health check and psychological treatment may be necessary for the prognosis of CHD patients who receive PCI.

J-Shaped Relationship Between Serum Prolactin and Metabolic-Associated Fatty Liver Disease in Female Patients With Type 2 Diabetes.

Background: Metabolic-associated fatty liver disease (MAFLD) has become a worldwide epidemic. Prolactin (PRL), a pituitary hormone, has been linked to MAFLD. As a result, we set out to look into the relationship between serum PRL and the risk of MAFLD in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 724 adults with T2DM were enrolled and categorized as MAFLD and non-MAFLD groups. Anthropometric data, biochemical parameters, and serum PRL levels were collected. Liver steatosis and fibrosis were assessed using FibroScan. Patients were stratified into normal PRL (NP) and high PRL (HP) groups and divided into four groups based on serum PRL quartiles. Multivariate logistic regression analysis was performed to evaluate the association between serum PRL and MAFLD risk. Results: Female but not male patients with MAFLD, liver steatosis, and fibrosis had significantly lower PRL levels in the NP group but higher PRL levels in the HP group than their counterparts. The proportions of MAFLD, liver steatosis, and fibrosis were significantly decreased in the NP group but increased in the HP group across the PRL quartiles in females but not in males. After multivariate adjustment, the adjusted ORs (AORs) and 95% CI for MAFLD among females were 18.165 (3.425-96.336), 1.784 (0.658-5.002), 1.744 (0.608-4.832), and 1.00 (reference) in the NP group (Q1-Q4, P-trend < 0.001) and 1.00 (reference), 11.098 (1.819-110.356), 15.225 (1.996-116.112), and 18.211 (2.579-128.568) in the HP group (Q1-Q4, P-trend = 0.020). Such associations were also found between serum PRL and liver fibrosis in females but not in males. Conclusion: We observed a J-shaped association between serum PRL and the risk of MAFLD and liver fibrosis in females but not in males with T2DM, indicating that PRL may be relevant to MAFLD and its progression in a gender-specific manner. Clinical Trial Registration: Chinese Clinical Trial Registry, number ChiCTR-OCS-12002381.

Detection of gadolinium deposition in cortical bone with ultrashort echo time T1 mapping: an ex vivo study in a rabbit model.

OBJECTIVES: To investigate the capacity of ultrashort echo time (UTE) T1 mapping to non-invasively assess gadolinium deposition in cortical bone after gadolinium-based contrast agent (GBCA) administration. METHODS: Twenty-eight New Zealand rabbits (male, 3.0-3.5 kg) were randomly allocated into control, macrocyclic, high-dose macrocyclic, and linear GBCA groups (n = 7 for each group), and respectively given daily doses of 0.9 ml/kg bodyweight saline, 0.3 mmol/kg bodyweight gadobutrol, 0.9 mmol/kg bodyweight gadobutrol, and 0.3 mmol/kg bodyweight gadopentetate dimeglumine for five consecutive days per week over a period of 4 weeks. After a subsequent 4 weeks of recovery, the rabbits were sacrificed and their tibiae harvested. T1 value of cortical bone was measured using a combination of UTE actual flip angle imaging and variable repetition time on a 7T animal scanner. Gadolinium concentration in cortical bone was measured using inductively coupled plasma mass spectrometry (ICP-MS). Pearson's correlation between R1 value (R1 = 1/T1) and gadolinium concentration in cortical bone was assessed. RESULTS: Bone T1 values were significantly lower in the lower-dose macrocyclic (329.2 ± 21.0 ms, p < 0.05), higher-dose macrocyclic (316.8 ± 21.7 ms, p < 0.01), and linear (296.8 ± 24.1 ms, p < 0.001) GBCA groups compared with the control group (356.3 ± 19.4 ms). Gadolinium concentrations measured by ICP-MS in the control, lower-dose macrocyclic, higher-dose macrocyclic, and linear GBCA groups were 0.04 ± 0.02 µg/g, 2.60 ± 0.48 µg/g, 4.95 ± 1.17 µg/g, and 13.62 ± 1.55 µg/g, respectively. There was a strong positive correlation between R1 values and gadolinium concentrations in cortical bone (r = 0.73, p < 0.001). CONCLUSIONS: These results suggest that UTE T1 mapping has the potential to provide a non-invasive assessment of gadolinium deposition in cortical bone following GBCA administration. KEY POINTS: • Changes in T1 value related to gadolinium deposition were found in bone after both linear and macrocyclic GBCA administrations. • R1 relaxometry correlates strongly with gadolinium concentration in cortical bone. • UTE T1 mapping provides a potential tool for non-invasively monitoring gadolinium deposition in cortical bone.

Who Misses Appointments Made Online? Retrospective Analysis of the Outpatient Department of a General Hospital in Jinan, Shandong Province, China.

PURPOSE: Missed appointments in outpatient registration pose challenges for hospital administrators, especially in the context of China's shortage of medical resources. Previous studies have identified factors that affect healthcare access via traditional appointment systems. Few studies, however, have specifically investigated Internet appointment systems. Therefore, this study explored the key factors related to missed appointments made on the Internet appointment system of a general hospital in Jinan, Shandong Province. METHODS: Online appointment data were collected from the outpatient department of a general hospital in Jinan from September 2017 to February 2018. Logistic regression was used to analyze the relative importance of eight variables: gender, age, interval between scheduling and appointment, day of the week, physician's academic rank, appointment fee, previous missed appointments, and clinical department. RESULTS: A total of 48,777 online appointment records were collected, which included a 15% no-show rate. The key factors associated with no-shows included age, interval between scheduling and appointment, previous missed appointments, and clinical department. No significant relationships were found between no-shows and gender, day of the week, and appointment fee. CONCLUSION: No-show rates were influenced by many factors. Based on this study's findings, targeted measures can be taken to decrease no-show frequency and improve medical efficiency.

Deep learning of lumbar spine X-ray for osteopenia and osteoporosis screening: A multicenter retrospective cohort study.

Osteoporosis is a prevalent but underdiagnosed condition. As compared to dual-energy X-ray absorptiometry (DXA) measures, we aimed to develop a deep convolutional neural network (DCNN) model to classify osteopenia and osteoporosis with the use of lumbar spine X-ray images. Herein, we developed the DCNN models based on the training dataset, which comprising 1616 lumbar spine X-ray images from 808 postmenopausal women (aged 50 to 92 years). DXA-derived bone mineral density (BMD) measures were used as the reference standard. We categorized patients into three groups according to DXA BMD T-score: normal (T ≥ -1.0), osteopenia (-2.5 < T < -1.0), and osteoporosis (T ≤ -2.5). T-scores were calculated by using the BMD dataset of young Chinese female aged 20-40 years as a reference. A 3-class DCNN model was trained to classify normal BMD, osteoporosis, and osteopenia. Model performance was tested in a validation dataset (204 images from 102 patients) and two test datasets (396 images from 198 patients and 348 images from 147 patients respectively). Model performance was assessed by the receiver operating characteristic (ROC) curve analysis. The results showed that in the test dataset 1, the model diagnosing osteoporosis achieved an AUC of 0.767 (95% confidence interval [CI]: 0.701-0.824) with sensitivity of 73.7% (95% CI: 62.3-83.1), the model diagnosing osteopenia achieved an AUC of 0.787 (95% CI: 0.723-0.842) with sensitivity of 81.8% (95% CI: 67.3-91.8); In the test dataset 2, the model diagnosing osteoporosis yielded an AUC of 0.726 (95% CI: 0.646-0.796) with sensitivity of 68.4% (95% CI: 54.8-80.1), the model diagnosing osteopenia yielded an AUC of 0.810 (95% CI, 0.737-0.870) with sensitivity of 85.3% (95% CI, 68.9-95.0). Accordingly, a deep learning diagnostic network may have the potential in screening osteoporosis and osteopenia based on lumbar spine radiographs. However, further studies are necessary to verify and improve the diagnostic performance of DCNN models.

Depletion of hepatic forkhead box O1 does not affect cholelithiasis in male and female mice.

Cholelithiasis is one of the most prevalent gastroenterological diseases and is characterized by the formation of gallstones in the gallbladder. Both clinical and preclinical data indicate that obesity, along with comorbidity insulin resistance, is a predisposing factor for cholelithiasis. Forkhead box O1 (FoxO1) is a key transcription factor that integrates insulin signaling with hepatic metabolism and becomes deregulated in the insulin-resistant liver, contributing to dyslipidemia in obesity. To gain mechanistic insights into how insulin resistance is linked to cholelithiasis, here we determined FoxO1's role in bile acid homeostasis and its contribution to cholelithiasis. We hypothesized that hepatic FoxO1 deregulation links insulin resistance to impaired bile acid metabolism and cholelithiasis. To address this hypothesis, we used the FoxO1LoxP/LoxP-Albumin-Cre system to generate liver-specific FoxO1-knockout mice. FoxO1-knockout mice and age- and sex-matched WT littermates were fed a lithogenic diet, and bile acid metabolism and gallstone formation were assessed in these animals. We showed that FoxO1 affected bile acid homeostasis by regulating hepatic expression of key enzymes in bile acid synthesis and in biliary cholesterol and phospholipid secretion. Furthermore, FoxO1 inhibited hepatic expression of the bile acid receptor farnesoid X receptor and thereby counteracted hepatic farnesoid X receptor signaling. Nonetheless, hepatic FoxO1 depletion neither affected the onset of gallstone disease nor impacted the disease progression, as FoxO1-knockout and control mice of both sexes had similar gallstone weights and incidence rates. These results argue against the notion that FoxO1 is a link between insulin resistance and cholelithiasis.

Serum FABP1 Levels Correlate Positively with Obesity in Chinese Patients After Laparoscopic Sleeve Gastrectomy: a 12-Month Follow-up Study.

OBJECTIVE: The role of liver fatty acid-binding protein (FABP1) in obesity is presently unclear. We investigated the association of FABP1 with obesity and the changes noted after laparoscopic sleeve gastrectomy (LSG) in a Chinese population. METHODS: The cross-sectional analysis included 187 individuals: 65 had normal weight (18.5 ≤ body mass index (BMI) < 24 kg/m2), 59 were overweight (24 ≤ BMI < 28 kg/m2), and 63 were obese (BMI ≥ 28 kg/m2). We also assessed 25 severely obese patients (BMI, 38.58 ± 4.59 kg/m2) at baseline and at 3, 6, and 12 months after LSG to observe FABP1 levels. RESULTS: FABP1 levels in the obese (30.33 ± 23.59 ng/ml, **P < 0.01, ***P < 0.001) and overweight (18.96 ± 18.75 ng/ml, P = 0.471) individuals were significantly higher than those in normal weight individuals (14.30 ± 9.37 ng/ml). Linear regression analysis revealed that the FABP1 levels were positively correlated with BMI (R2 = 0.201, ***P < 0.001), ALT (R2 = 0.324, ***P < 0.001), AST (R2 = 0.387, ***P < 0.001), m-AST (R2 = 0.160, ***P < 0.001), γ-GT (R2 = 0.106, ***P < 0.001), DBil (R2 = 0.078, ***P < 0.001), UA (R2 = 0.111, ***P < 0.001), FBG (R2 = 0.066, ***P < 0.001), LDL (R2 = 0.042, **P = 0.005), and were negatively correlated with HDL (R2 = 0.051, **P = 0.002). After adjusting for age, sex, ALT, AST, TC, TG, HDL, LDL, FBG, and UA, FABP1 was independently correlated with BMI (*P < 0.05). With decreasing BMI after LSG, the FABP1 levels (29.46 ± 21.19 ng/ml, P = 0.463, P = 0.06, *P < 0.05) also decreased at 3 (23.00 ± 22.77 ng/ml), 6 (14.41 ± 15.48 ng/ml), and 12 months (11.55 ± 3.27 ng/ml). CONCLUSION: Serum FABP1 levels are closely correlated with obesity and many metabolic factors, and we found that with the decrease in BMI after LSG, the FABP1 levels also progressively decreased postoperatively. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ChiCTR-OCS-12002381.

Circulating osteocalcin: A potential predictor of ketosis in type 2 diabetes.

AIMS: Osteocalcin contributes to the regulation of endocrine system. However, the association between osteocalcin and ketosis has not been evaluated. We thus aimed to explore the relationship between total osteocalcin and risk of ketosis in type 2 diabetes (T2DM). MATERIALS AND METHODS: We identified 6157 diabetes patients from Shanghai Tenth People's Hospital between 1 January 2011 and 1 March 2017. Six hundred eight subjects were enrolled in the retrospective cross-sectional study: 304 T2DM patients with ketosis whose age, gender, and body mass index were matched with 304 T2DM patients without ketosis. A further retrospective nested case-control study was conducted in 252 T2DM patients without ketosis for a mean duration of 21.58 ± 12.43 months to investigate the occurrence of ketosis. RESULTS: Osteocalcin levels were negatively correlated with blood ketones (adjusted r = -0.263) and urine ketones (adjusted r = -0.183). The inverse dose-dependent relationship of osteocalcin and risk of ketosis was present across osteocalcin level quintiles (top quintile as the reference, adjusted odds ratio [95% CI] = 2.56 [0.80-8.17], 3.71 [0.90-15.29], 10.77 [2.63-44.15], 23.81 [4.32-131.17] per osteocalcin quintile, respectively). Ketosis occurred in 17 of the 252 T2DM patients during follow-up. The Cox regression analysis indicated that osteocalcin was an independent protective factor against development of ketosis (adjusted hazard ratio [95% CI]: 0.668 [0.460-0.971]). CONCLUSIONS: Total osteocalcin can be used as a predictor of ketosis in T2DM.

Reduction in Thyroid-Stimulating Hormone Correlated with Improved Inflammation Markers in Chinese Patients with Morbid Obesity Undergoing Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: Bariatric surgery has a significant impact on levels of thyroid hormones and various inflammatory markers in obesity. The relationship between changes in thyroid hormones and inflammatory markers after bariatric surgery is unknown. We aimed to investigate the changes in thyroid hormones and their relations to inflammatory changes after laparoscopic sleeve gastrectomy (LSG) in Chinese patients with morbid obesity. METHODS: Eighty-eight patients with morbid obesity (56.8% female; age 30.9 ± 9.5 years; BMI 39.9 ± 5.7 kg/m2) submitted to LSG were selected. Patients were subdivided into euthyroid group and subclinical hypothyroidism (SH) group. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), inflammatory markers, and related metabolic indexes were analyzed pre- and 12 months post-LSG. RESULTS: SH patients presented significantly higher interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) than euthyroid patients. Twelve-month post-surgery, the SH incidence decreased from 31.8 to 2.3% (P < 0.001). TSH levels were declined significantly in both groups but were more pronounced in SH group (P < 0.001), whereas no change in FT4 in either group. Additionally, we observed marked reduction of IL-6, TNF-α, and CRP in SH group, as well as TNF-α and CRP in euthyroid group. After adjusting for age, baseline BMI, and changes in BMI, decrease in TSH correlated significantly with decreased HOMA-IR and TNF-α in euthyroid group and decreased fasting insulin (FINS), IL-6, TNF-α, and CRP in SH group. CONCLUSION: LSG promotes TSH reduction in patients with morbid obesity that is more pronounced in patients with SH and correlated with improved inflammatory state after surgery.

Changes in inflammatory markers correlated with increased testosterone after laparoscopic sleeve gastrectomy in obese Chinese men with acanthosis nigricans.

Bariatric surgery is an effective method for severe obesity and its related comorbidities. This study was performed to explore the alterations of sex hormones and inflammatory markers following laparoscopic sleeve gastrectomy (LSG) among obese Chinese men with acanthosis nigricans (AN). Sixty-five obese men who underwent LSG were enrolled, comprising simple obesity without AN (OB group, n = 20) and obesity with AN (AN group, n = 45). There were 31 healthy male controls with normal body mass index (BMI) included. Anthropometry data, inflammatory markers, sex hormones and metabolic parameters were compared preoperatively and 12 months post-operatively. At baseline, patients in the AN group were associated with more severe metabolic abnormalities than the OB and control groups. Twelve months after surgery, AN patients obtained significant improvement in skin condition and reduction in AN score. BMI, fasting insulin (FINS), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), tumor necrosis factor-α (TNF-α) and total testosterone (TT) were significantly changed in both groups, while interleukin (IL)-6, IL-8 and C-reactive protein were changed significantly only in the AN group. Moreover, FINS, HOMA-IR, TT and IL-6 levels were changed more in the AN group than those in the OB group. Multivariate regression analysis revealed that TT increase correlated significantly with reduction in FINS and HOMA-IR in both groups, but correlated with changes in IL-6 only in the AN group. In conclusion, LSG is effective in improving the skin condition of obese men with AN. The increased TT in AN patients correlated with amelioration of inflammatory state in addition to insulin resistance after LSG.

Changes in Sex Hormones After Laparoscopic Sleeve Gastrectomy in Chinese Obese Men: a 12-Month Follow-Up.

BACKGROUND: To examine changes in sex hormones after laparoscopic sleeve gastrectomy (LSG) in Chinese obese male patients and their correlation with metabolic parameters including serum uric acid (SUA) METHODS: A total of 56 obese men with body mass index (BMI) 41.9 ± 5.8 kg/m2 undergoing LSG were selected. Thirty-one healthy men with normal BMI were included as controls. Levels of total testosterone (TT), estradiol (E2), sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), SUA, and other metabolic indices were compared pre- and 12 months post-LSG. Calculated free testosterone (cFT) was calculated from TT and SHBG using an empirical equation. RESULTS: At baseline, low TT and hyperuricemia (HUA) were common in obese men. Twelve months after LSG, statistically significant reduction in weight, BMI, and glucolipid metabolism indices was noted. SUA levels declined remarkably from 474.9 ± 94.6 to 338.8 ± 81.9 µmol/L and the percentage of HUA decreased from 76.8 to 54.1% (all P < 0.001). Additionally, significant increases in TT, SHBG, and cFT as well as a decrease in percentage of low TT were observed after LSG (all P < 0.05), while E2, FSH, and LH did not change significantly. Moreover, changes in TT levels were more pronounced than those of other sex hormones. After age and BMI were adjusted, increased TT levels were correlated significantly with decreased SUA (ß = - 1.077, P < 0.05), BMI (ß = - 0.712, P < 0.001), and HOMA-IR (ß = - 0.652, P < 0.05), as well as increased SHBG (ß = 0.759, P < 0.001). CONCLUSIONS: LSG promotes a significant increase in TT levels in Chinese obese men, which may be mediated by substantial weight loss, SUA reduction, and improved insulin resistance (IR).

Key pathway and gene alterations in the gastric mucosa associated with obesity and obesity-related diabetes.

BACKGROUND AND OBJECTIVE: The stomach plays an important role in obesity and obesity-related diabetes; yet, little is known about key pathways in the gastric mucosa associated with obesity and diabetes. METHODS: We performed gene microarray and real time-polymerase chain reaction (RT-PCR) on gut mucosa samples from control subjects (CON), patients with simple obesity (OB), and patients with obesity and comorbid diabetes (OD) (n = 3 per group). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the functional significance of differentially expressed genes. RESULTS: In total, 262 genes were upregulated and 265 genes were downregulated in the OB group whereas 1756 genes were upregulated and 1053 genes were downregulated in the OD group compared with the CON group. Of these, 23 were co-regulated in both comparisons. Seven differentially expressed genes were validated by RT-PCR (NRIP3, L1CAM, TPO, P2RY1, OR8A1, ADAMTS19, and ASIC3). A functional analysis revealed that genes differentially expressed between the OB or OD and CON groups played crucial roles in metabolic, T cell, and G-protein coupled receptor biological processes, and primarily participated in the PI3K-Akt and AGE-RAGE signaling pathways. CONCLUSIONS: Obesity and obesity-related diabetes are associated with important gene expression and pathway alterations in the stomach.