Anaemia in patients with self-reported use of iron supplements in the BAriatric surgery SUbstitution and nutrition study: A prospective cohort study.

BACKGROUND AND AIMS: After bariatric surgery, micronutrient deficiencies may lead to anaemia. To prevent post-operative deficiencies, patients are recommended lifelong micronutrient supplementation. Studies investigating the effectiveness of supplementation to prevent anaemia after bariatric surgery are scarce. This study aimed to investigate the relationship between nutritional deficiencies and anaemia in patients who report use of supplementation two years after bariatric surgery versus patients who do not. METHODS AND RESULTS: Obese (BMI≥35 kg/m2) individuals (n = 971) were recruited at Sahlgrenska University Hospital in Gothenburg, Sweden between 2015 and 2017. The interventions were Roux-en-Y gastric bypass (RYGB), n = 382, sleeve gastrectomy (SG), n = 201, or medical treatment (MT), n = 388. Blood samples and self-reported data on supplements were collected at baseline and two years post treatment. Anaemia was defined as haemoglobin <120 g/L for females and <130 g/L for males. Standard statistical methods, including a logistic regression model and a machine learning algorithm, were used to analyse data. The frequency of anaemia increased from baseline in patients treated with RYGB (3·0% vs 10·5%; p < 0·05). Neither iron-dependent biochemistry nor frequency of anaemia differed between participants who reported use of iron supplements and those who did not at the two-year follow-up. Low preoperative level of haemoglobin and high postoperative percent excessive BMI loss increased the predicted probability of anaemia two years after surgery. CONCLUSION: The results from this study indicate that iron deficiency or anaemia may not be prevented by substitutional treatment per current guidelines after bariatric surgery and highlights there is reason to ensure adequate preoperative micronutrient levels. TRIAL REGISTRATION: March 03, 2015; NCT03152617.

Impact of Medical and Surgical Obesity Treatment on Dental Caries: A 2-Year Prospective Cohort Study.

The objective was to study the long-term effects on oral health of bariatric surgery compared with medical treatment of obesity. Swedish females with morbid obesity (n = 66; 18-35 years at baseline) were followed prospectively from before obesity treatment until 2 years after treatment. The main response variable was dental caries registered according to the ICDAS-II system. Possible confounding factors, such as sociodemographic characteristics, general health, oral health habits, and oral hygiene, were controlled for. The statistical methods included χ2 tests, Student's t tests, one-way ANOVA, Wilcoxon's nonparametric tests, and linear regression models. In the surgically treated patients (n = 40), a significant increase over time in enamel caries (mean increase 4.13 tooth surfaces ICDAS1-2), dentine caries (mean increase 2.18 tooth surfaces ICDAS3-6), and total caries (mean increase 6.30 tooth surfaces ICDAS1-6) was registered (all p < 0.001), which was not seen in the medically treated patients (n = 26). However, the difference between the treatment groups (surgical or medical) was only statistically significant for enamel caries (crude ß 4.89, p = 0.003) and total caries (crude ß 6.53, p < 0.001). The relationships were stable and independent of differences in confounders as socioeconomy, general health, and oral health behaviors. In conclusion, 2 years after obesity treatment, a significant increase in dental caries was registered in the surgically treated but not in the medically treated women. The dental service should intensify its preventive efforts in individuals undergoing obesity treatment.

Changes in physical and mental health in Swedish schoolchildren in the digital age.

AIM: Poor physical and mental health are common and increasing in Swedish children. The aim was to investigate significant changes in health and digital habits in fourth grade and ninth grade pupils in 2020 compared to 2011. METHODS: A validated questionnaire was conducted in 2011 and 2020 among schoolchildren in fourth (10 years) and ninth grade (15 years) in Sweden. The study population consisted of 196 students in 2020 and 254 students in 2011. RESULTS: A significant increase was seen in self-reported sleeping difficulties, tiredness, life dissatisfaction and dissatisfaction with academic abilities among fourth grade children and a sixfold increase in their refusal to go to school. Students in fourth grade also reported that they spent more time on social media and had a reduced interest in sports. Both students in fourth and ninth grade described an increase in attacks of anger and unhappiness, as well as decreased time with family. CONCLUSION: We conclude that fourth grade children have more physical and mental health symptoms in 2020 compared to 2011. The ninth grade students showed a high frequency of physical and mental symptoms in 2011, which remained high in 2020. One possible explanation may be that digital habits have increased.

Prevalence of dry mouth in adult patients in primary health care.

OBJECTIVES: To determine the prevalence and severity of dry mouth by age, gender, presence of disease, and medication intake for patients aged 18 years and over, seeking primary health care on the west coast of Sweden (Region of Västra Götaland, VGR). MATERIALS AND METHODS: Cross-sectional study conducted among patients (n = 374, age ≥ 18) visiting primary health care providers (n = 4) in VGR for any medical reasons. Patients were invited to participate by answering a single-item question, 'Have you experienced dry mouth in the last six months?' Patients giving positive answers (n = 163) were asked to fill in the 11-item Xerostomia Inventory (XI) questionnaire to determine the variability and severity of xerostomia. Patients replying 'No' (n = 211) to the single-item question were considered not to have xerostomia and included in the non-xerostomia group. RESULTS: The overall prevalence of xerostomia was 43.6% with a female dominance (61.2%). The prevalence in different age groups among females and males was similar. The number of medications and/or diseases are positively associated with xerostomia. Medication was a significant predictor of the prevalence of xerostomia, regardless of age and gender (p < .001). Patients with five or more medications had the highest prevalence of xerostomia (71.2%). CONCLUSION: Patients seeking primary care on the west coast of Sweden have a high prevalence of xerostomia. Factors associated with xerostomia were female gender and medications and/or diseases. Awareness is required to manage patients with xerostomia in medical and dental care.

Oral health by obesity classification in young obese women - a cross-sectional study.

OBJECTIVE: To explore oral health by increasing degree of obesity and the influence of modifying factors. MATERIALS AND METHODS: A cross-sectional design was used. Swedish females (n = 118; 18-35 years) with morbid obesity were recruited from the BAriatric SUbstitution and Nutrition study (BASUN). Body mass index (BMI) was used as continuous and categorized into 35-39.9 kg/m2/40-44.9 kg/m2/≥45 kg/m2. Oral examinations assessed dental caries using the ICDAS system, periodontal status and saliva characteristics. Information on sociodemographics, oral health behaviour and symptoms was collected via a questionnaire. RESULTS: Mean BMI was 42.2 kg/m3 (SD 4.0; range 35.0-63.7). Significantly higher frequencies of dentine caries (p = .001) and total caries (p = .046) were found with higher BMI with an increase in total caries by 0.59 tooth surface (p = .025) for each increasing BMI degree. There were consistent associations between obesity and dentine caries for the group with the highest BMI (≥45), adjusted RR 2.08 (95% CI 1.20-3.61), and all stages of caries, adjusted RR 1.41 (95% CI 1.02-1.96). High scores were found for dental plaque (50.2%) and gingivitis (34.5%). CONCLUSION: Young obese women exhibited poor oral health with higher caries levels by higher BMI. Dental care should adapt the prevention efforts for obese individuals. Trial Registration: The trial was prospectively registered on March 03; 2015; NCT03152617.

The BAriatic surgery SUbstitution and nutrition (BASUN) population: a data-driven exploration of predictors for obesity.

BACKGROUND: The development of obesity is most likely due to a combination of biological and environmental factors some of which might still be unidentified. We used a machine learning technique to examine the relative importance of more than 100 clinical variables as predictors for BMI. METHODS: BASUN is a prospective non-randomized cohort study of 971 individuals that received medical or surgical treatment (treatment choice was based on patient's preferences and clinical criteria, not randomization) for obesity in the Västra Götaland county in Sweden between 2015 and 2017 with planned follow-up for 10 years. This study includes demographic data, BMI, blood tests, and questionnaires before obesity treatment that cover three main areas: gastrointestinal symptoms and eating habits, physical activity and quality of life, and psychological health. We used random forest, with conditional variable importance, to study the relative importance of roughly 100 predictors of BMI, covering 15 domains. We quantified the predictive value of each individual predictor, as well as each domain. RESULTS: The participants received medical (n = 382) or surgical treatment for obesity (Roux-en-Y gastric bypass, n = 388; sleeve gastrectomy, n = 201). There were minor differences between these groups before treatment with regard to anthropometrics, laboratory measures and results from questionnaires. The 10 individual variables with the strongest predictive value, in order of decreasing strength, were country of birth, marital status, sex, calcium levels, age, levels of TSH and HbA1c, AUDIT score, BE tendencies according to QEWPR, and TG levels. The strongest domains predicting BMI were: Socioeconomic status, Demographics, Biomarkers (notably TSH), Lifestyle/habits, Biomarkers for cardiovascular disease and diabetes, and Potential anxiety and depression. CONCLUSIONS: Lifestyle, habits, age, sex and socioeconomic status are some of the strongest predictors for BMI levels. Potential anxiety and / or depression and other characteristics captured using questionnaires have strong predictive value. These results confirm previously suggested associations and advocate prospective studies to examine the value of better characterization of patients eligible for obesity treatment, and consequently to evaluate the treatment effects in groups of patients. TRIAL REGISTRATION: March 03, 2015; NCT03152617 .

Design and baseline data in the BAriatic surgery SUbstitution and Nutrition study (BASUN): a 10-year prospective cohort study.

BACKGROUND: There is still a lack of knowledge on long-term effects of surgical and non-surgical weight-lowering treatments. BASUN is a prospective study with 10 years of follow-up that will observe the effects and consequences of surgical and medical treatment of obesity. The aims are to cover areas where data on long-term outcomes are lacking, e.g., nutritional deficiencies, substance abuse, psychiatric health, as well as patient-reported outcomes. METHODS: BASUN is a cohort study that recruited study persons with obesity (BMI ≥ 35 kg/m2) referred to the Regional Obesity Centre of Region Västra Götaland. The interventions were Roux-en-Y gastric bypass (RYGB) or Sleeve gastrectomy (SG), or 12 months of structured, multi-professional medical treatment (MT), including very low energy diet, followed by diet and pharmaceutical treatment. The study is not randomized, but based on patients preferences and multidisciplinary assessments. The study persons are examined at baseline, 2, 5, and 10 years with blood tests, measurements and questionnaires. The recruitment period lasted from May 2015 to November 2017. RESULTS: One thousand one hundred twenty-seven patients were included (74% female). Three hundred eighty-two patients were accepted for medical treatment, 589 for surgical treatment (388 RYGB and 201 SG) and 156 patients left the study without treatment, leaving a final study population of 971 patients. There were slight differences between the treatment groups with regards to age and BMI. Pharmaceutical treatments, level of education, smoking and marital status were not significantly different between the groups. CONCLUSION: This study will follow 971 obese subjects in clinical practice treated with the best surgical or medical methods currently available. It has the potential to evaluate outcomes usually not reported in short-term studies, and to assist in identifying factors that are of importance for the choices of treatment. The main limitations are non-randomization and differences in baseline characteristics. The large number of participants and the length of the prospective follow-up are major strengths of the study. BASUN is designed to identify both early and late benefits and adverse events of treatment of obesity. TRIAL REGISTRATION: This trial was prospectively registered on March 03, 2015; NCT03152617.

Normalization of qPCR in platelets - YWHAE a potential genericreference gene.

The mRNA of human platelets has been extensively studied and it is generally appreciated that platelets contain mRNA transcripts derived from the megakaryocytes, and they have the ability to translate it into proteins. Additionally, platelets contain microRNA (miRNA) that has been shown to potentially regulate the translation of certain proteins. When quantifying gene expression by quantitative real-time polymerase chain reaction (qPCR), a valid normalization method is required and the use of reference genes is a common and robust approach. It is recommended to perform a proper validation of potential reference genes for each individual experimental setup. Previous studies have mainly been performed using commonly used reference genes for nucleated cells, and to our knowledge there are no global evaluations of the stability of transcripts in platelets. Finding a stable transcript would be valuable for inter-study comparisons, and the aim of this study was to identify one or more stable mRNA transcripts suitable as generic reference genes for mRNA gene expression studies in platelets. Platelets were incubated for 24 h and microarray of platelet mRNA revealed that the levels of YWHAE, B2M, ITM2B, H3F3A, PF4V1 remained similar between 0 and 24 h. Further validation of the stability of these genes together with GAPDH, RN18S1, and PPIA, genes frequently used as reference genes in platelet studies, was performed using qPCR after different in vitro conditions. In addition, inter-individual stability of the genes was analyzed in diabetic patients compared with healthy matched controls. Analysis of gene stability by the software RefFinder revealed that YWHAE, PF4V1, and B2M were the most stable genes in platelets from healthy donors. In addition, YWHAE was stable between subjects. Furthermore, the potential influence of miRNA on the selected genes was investigated by knockdown of Dicer1 in the megakaryocytic cell line MEG01. YWHAE, H3F3A, B2M, and GAPDH remained unchanged over time in MEG01 cells indicating that these genes are not regulated by miRNA and hence are more stably expressed. In conclusion, YWHAE is a stable transcript in platelets and we suggest the use of YWHAE as a generic reference gene in mRNA gene expression studies.

Effects of medical and surgical treatment on vitamin D levels in obesity.

INTRODUCTION: Persons living with obesity treated with bariatric surgery are at a high risk of developing nutritional deficiencies. The primary aim of this observational cohort study was to compare vitamin D levels in patients two years after bariatric surgery (Roux-en-Y gastric bypass/RYGB and sleeve gastrectomy/SG) with a very low-energy diet (VLED). The same subjects were also compared with a population sample from the same region at baseline. The primary hypothesis was that surgery, especially RYGB, would lead to an increased prevalence of vitamin D deficiency compared to subjects treated with VLED. 971 individuals eligible for surgical, RYGB (n = 388), SG (n = 201), and medical treatment (n = 382), in routine care, were included consecutively between 2015 and 2017. A random population sample from the WHO-MONICA project was used as a reference, (n = 414). S-calcium, S-25(OH)D (vitamin D), and S-PTH (parathyroid hormone) were measured in all persons with obesity at baseline and two years after treatment (n = 713). Self-reported use of vitamin D and calcium supplementation was registered. RESULTS: Vitamin D deficiency (S-25(OH)D <25mmol/l) was found in 5.2% of the persons with obesity at baseline versus 1.7% of the general population (SMD>0.1). S-25(OH)D increased for all treatment groups but was higher in RYGB and SG (SMD>0.1, standardized mean difference). Thirteen subjects (1.8%) had vitamin D deficiency after obesity treatment. CONCLUSION: Surgical intervention for obesity followed by vitamin D supplementation was not associated with a higher risk for vitamin D deficiency, irrespective of surgery type, compared to individuals on medical treatment. However, persons living with obesity seeking weight loss treatment are more likely to have deficient vitamin D levels compared to the general population.

Comparing effects of obesity treatment with very low energy diet and bariatric surgery after 2 years: a prospective cohort study.

OBJECTIVES: To compare long-term effects and complications of medical treatment (MT) of obesity including very low energy diet with bariatric surgery. DESIGN AND SETTING: This prospective study conducted in a clinical setting recruited individuals with body mass index (BMI) ≥35 kg/m2 referred for obesity treatment. Demographic and anthropometric data, laboratory samples, and questionnaire replies were collected at baseline and 2 years. PARTICIPANTS AND INTERVENTIONS: 971 individuals were recruited 2015-2017. 382 received MT, 388 Roux-en-Y gastric bypass (RYGB) and 201 sleeve gastrectomy (SG). MAIN OUTCOME MEASURES: Primary outcomes included changes in anthropometric measures, metabolic variables and safety. These were analysed using a linear regression model. A logistic regression model was used to analyse composite variables for treatment success (secondary outcomes). A random forest (RF) model was used to examine the importance of 15 clinical domains as predictors for successful treatment. RESULTS: Two-year data were available for 667 individuals (68.7%). Regarding primary outcomes, the decrease in excess BMI was 27.5%, 82.5% and 70.3% and proportion achieving a weight of >10% was 45.3%, 99.6% and 95.6% for MT, RYGB and SG, respectively (p<0.001). The groups were comparable regarding levels of vitamins, minerals and haemoglobin or safety measures. Likelihood for success (secondary outcome) was higher in the surgical groups (RYGB: OR 5.3 (95% CI 3.9 to 7.2) vs SG: OR 4.3 ((95% CI 3.0 to 6.2)) in reference to MT. Baseline anthropometry had the strongest predictive value for treatment success, according to the RF model. CONCLUSIONS: In clinical practice, bariatric surgery by RYGB or SG is most effective, but meaningful weight loss is achievable by MT with strict caloric restriction and stepwise introduction of a normal diet. All treatments showed positive effects on well-being, cardiovascular risk factors, and levels of vitamins and minerals at 2-year follow-up and groups were similar regarding safety measures. TRIAL REGISTRATION NUMBER: NCT03152617.

The role of the platelet pool of Plasminogen Activator Inhibitor-1 in well-controlled type 2 diabetes patients.

BACKGROUND: The main inhibitor of the fibrinolytic system, Plasminogen Activator Inhibitor -1 (PAI-1), irreversibly binds tissue-type Plasminogen Activator (t-PA) and thereby inhibits the protective action of tPA against thrombus formation. Elevated levels of plasma PAI-1 are associated with an increased risk of cardiovascular events and are observed in subjects with type 2 diabetes (T2D) and obesity. Platelets contain the majority of PAI-1 present in blood and exhibit the ability to synthesis active PAI-1. Diabetic platelets are known to be hyper-reactive and larger in size; however, whether these features affect their contribution to the elevated levels of plasma PAI-1 in T2D is not established. OBJECTIVES: To characterize the PAI-1 antigen content and the mRNA expression in platelets from T2D subjects compared to obese and lean control subjects, in order to elucidate the role of platelet PAI-1 in T2D. METHODS: Nine subjects with T2D and obesity were recruited from Primary Care Centers together with 15 healthy control subjects (8 lean subjects and 7 with obesity). PAI-1 antigen levels in plasma, serum and platelets were determined by ELISA, and PAI-1 mRNA expression was analyzed by qPCR. RESULTS: There was no significant difference in PAI-1 mRNA expression or PAI-1 antigen in platelets in T2D subject in comparison to obese and lean control subjects. An elevated level of plasma PAI-1 was seen in both T2D and obese subjects. PAI-1 gene expression was significantly higher in both obese groups compared to lean. CONCLUSION: Similar levels of protein and mRNA expression of PAI-1 in platelets from T2D, obese and lean subjects indicate a limited role of platelets for the elevated plasma PAI-1 levels. However, an increased synthesis rate of mRNA transcripts in platelets from T2D and an increased release of PAI-1 could also result in similar mRNA and protein levels. Hence, synthesis and release rates of PAI-1 from platelets in T2D and obesity need to be investigated to further elucidate the role of platelets in obesity and T2D.

Comorbidity and quality of life in obesity-a comparative study with the general population in Gothenburg, Sweden.

CONTEXT: Obesity is considered to have a detrimental impact on health-related quality of life (HRQoL). OBJECTIVE: To compare HRQoL in a well-defined group of people with obesity with a population-based control group from the general public. DESIGN: Observational cross-sectional cohort study with a reference population. SETTING: The Regional Obesity Center at the Department of Medicine at Sahlgrenska University Hospital, Gothenburg, Sweden. PARTICIPANTS: People with obesity (n = 1122) eligible for surgical and non-surgical obesity treatment in routine care were included consecutively between 2015 and 2017 into the BASUN study. Men and women from the WHO-MONICA-GOT project were used as a reference population (n = 414). MAIN OUTCOME MEASURES: HRQoL was measured with the RAND-36/Short Form-36 questionnaire (SF-36) and a Visual Analogue Scale (VAS) for self-related health (SRH). Prescription drugs for hypertension, diabetes mellitus, depression, and anxiety were taken as a proxy for these conditions. RESULTS: People with obesity rated their overall HRQoL lower than the reference population according to the SRH-VAS. Lower scores were reported on physical and social functioning, vitality, general and mental health after adjustment for age and use of prescription drugs (considered a proxy for burden of disease, or comorbidities) using the RAND-36/SF-36 questionnaire. Use of some psychopharmacological agents was more common in patients with obesity. CONCLUSION: People with obesity seeking help with weight reduction are more likely to have lower physical and mental self-reported HRQoL than the general population.

Oral health profile of postbariatric surgery individuals: A case series.

OBJECTIVES: To describe the oral health profile of individuals who had undergone gastric bypass surgery (GBP) or sleeve gastrectomy (SG) to generate hypotheses for further studies. MATERIAL AND METHODS: Fourteen individuals treated with GBP or SG surgery ≥ 2 years ago and with observed and/or perceived oral problems were recruited to a case series. The documentation included clinical and radiographic examinations, biomedical sampling, and self-reported diet and questionnaires. The results are presented descriptively. RESULTS: The age range was 31 to 66 years and all had a BMI > 25 (range 25.4-44.7). Only four participants were fully dentate. Eleven out of 14 individuals exhibited severe decay. A majority had poor oral hygiene and high bacterial counts. The flow rates of unstimulated saliva were extremely low and hyposalivation was present in ten of the fourteen cases. Most perceived several oral health problems, such as chewing difficulty and tooth hypersensitivity. CONCLUSIONS: Individuals who had undergone GBP or SG surgery had poor clinically diagnosed oral health and perceived oral health problems. Longitudinal studies are needed to monitor the patients' oral health, from before bariatric surgery to long-term postoperatively.

Hyperinsulinemia and insulin resistance in the obese may develop as part of a homeostatic response to elevated free fatty acids: A mechanistic case-control and a population-based cohort study.

BACKGROUND: It is commonly accepted that in obesity free fatty acids (FFA) cause insulin resistance and hyperglycemia, which drives hyperinsulinemia. However, hyperinsulinemia is observed in subjects with normoglycaemia and thus the paradigm above should be reevaluated. METHODS: We describe two studies: MD-Lipolysis, a case control study investigating the mechanisms of obesity-driven insulin resistance by a systemic metabolic analysis, measurements of adipose tissue lipolysis by microdialysis, and adipose tissue genomics; and POEM, a cohort study used for validating differences in circulating metabolites in relation to adiposity and insulin resistance observed in the MD-Lipolysis study. FINDINGS: In insulin-resistant obese with normal glycaemia from the MD-Lipolysis study, hyperinsulinemia was associated with elevated FFA. Lipolysis, assessed by glycerol release per adipose tissue mass or adipocyte surface, was similar between obese and lean individuals. Adipose tissue from obese subjects showed reduced expression of genes mediating catecholamine-driven lipolysis, lipid storage, and increased expression of genes driving hyperplastic growth. In the POEM study, FFA levels were specifically elevated in obese-overweight subjects with normal fasting glucose and high fasting levels of insulin and C-peptide. INTERPRETATION: In obese subjects with normal glycaemia elevated circulating levels of FFA at fasting are the major metabolic derangement candidate driving fasting hyperinsulinemia. Elevated FFA in obese with normal glycaemia were better explained by increased fat mass rather than by adipose tissue insulin resistance. These results support the idea that hyperinsulinemia and insulin resistance may develop as part of a homeostatic adaptive response to increased adiposity and FFA. FUNDING: Swedish-Research-Council (2016-02660); Diabetesfonden (DIA2017-250; DIA2018-384; DIA2020-564); Novo-Nordisk-Foundation (NNF17OC0027458; NNF19OC0057174); Cancerfonden (CAN2017/472; 200840PjF); Swedish-ALF-agreement (2018-74560).

Differential response of plasma plasminogen activator inhibitor 1 after weight loss surgery in patients with or without type 2 diabetes.

BACKGROUND: Obesity and type 2 diabetes (T2D) are associated with a suppression of fibrinolysis and an increased risk of intravascular thrombi because of elevated plasma plasminogen activator inhibitor 1 (PAI-1). OBJECTIVES: The aim was to investigate PAI-1 levels in obese patients in the early phase after bariatric surgery, before any weight loss, and in the late phase, to identify the impact of reduced adipose mass versus weight loss independent effects on PAI-1 levels. We also studied the impact of T2D on the rate of PAI-1 reduction. SETTINGS: Twelve obese patients with and without T2D (n = 6) who were scheduled for surgery at a designated Center of Excellence. METHODS: Plasma PAI-1 antigen was measured by enzyme-linked immunosorbent assay (ELISA) preoperatively and at 4 and 42 days after gastric bypass surgery. RESULTS: In the early phase, plasma PAI-1 was significantly decreased by 53% (P = .023). This difference did not remain significant in the late phase. However, PAI-1 levels in T2D and non-T2D patients were significantly different (P = .005). In non-T2D patients, plasma PAI-1 levels decreased significantly in both early and late phases (P = .038). Interestingly, in the T2D group, the PAI-1 levels tended to increase in the late phase and differed significantly from the non-T2D group. CONCLUSION: We report decreased PAI-1 levels in the immediate postoperative period after gastric bypass, indicating that a mechanism not related to the fat mass regulates the PAI-1 levels. Additionally, there may be a difference in PAI-1 levels between T2D and non-T2D patients 42 days postoperatively. Further studies are required to verify this difference and to elucidate the specific mechanisms responsible for PAI-1 synthesis.