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Turkish Journal of Medical Sciences 2023This study was designed to evaluate the relationship of two new biomarkers [tribbles homolog 3 (TRB3) and sestrin 2 levels], which were previously associated with...
BACKGROUND/AIM
This study was designed to evaluate the relationship of two new biomarkers [tribbles homolog 3 (TRB3) and sestrin 2 levels], which were previously associated with obesity, with metabolic parameters in obese and nonobese women with polycystic ovary syndrome (PCOS).
MATERIALS AND METHODS
This cross-sectional case control study was conducted between September 2017 and August 2019 in the gynecology department of a tertiary referral hospital. The values of the plasma sestrin 2, TRB3, insulin, fasting plasma glucose, lipid profile, and homeostasis model assessment of insulin resistance (HOMA-IR) were compared in 90 obese women with PCOS (BMI > 30), 90 women with nonobese PCOS (BMI < 30), and 90 control patients (BMI < 30).
RESULTS
The mean age of the study group consisting of all PCOS patients (26.11 ± 4.64 years) and the mean age of the control group (26.3 ± 4.4 years) were statistically similar (p = 0.239). The serum sestrin 2 values of the obese PCOS group were found to be statistically significantly lower than the control and non-obese PCOS groups (p = 0.001, p = 0.0001), while the sestrin 2 values of the nonobese PCOS group were found to be statistically significantly lower than the control group (p = 0.0001). The TRB3 values of the control group were found to be statistically significantly lower than the obese and nonobese PCOS groups (p = 0.0001), while the TRB3 values of the nonobese PCOS group were found to be statistically significantly lower than the obese PCOS group (p = 0.0001). A negative correlation was observed between the sestrin 2 level and BMI (r = -0.272 p = 0.0001), insulin (r = -0.261 p = 0.0001), and HOMA-IR levels (r = -0.250 p = 0.0001). A positive correlation was observed between the TRB3 values and TG (r = 0.248 p = 0.0001), and LDL-C values (r = 0.235 p = 0.0001).
CONCLUSION
According to the findings in this study, low sestrin 2 and high TRB3 levels may be related to impaired metabolic status in the obese PCOS group. Thus, it may be promising for the development of treatment of PCOS and associated metabolic disorder in the future.
Topics: Humans; Female; Polycystic Ovary Syndrome; Obesity; Adult; Case-Control Studies; Cross-Sectional Studies; Protein Serine-Threonine Kinases; Biomarkers; Insulin Resistance; Nuclear Proteins; Young Adult; Blood Glucose; Sestrins; Repressor Proteins; Cell Cycle Proteins
PubMed: 38813505
DOI: 10.55730/1300-0144.5738 -
Frontiers in Public Health 2024Increasing evidence supports chronic psychological stress as a risk factor for the development of type 2 diabetes. Much less is known, however, about the role of chronic...
INTRODUCTION
Increasing evidence supports chronic psychological stress as a risk factor for the development of type 2 diabetes. Much less is known, however, about the role of chronic stress in established diabetes.
METHODS
The aim of the current study was to comprehensively assess chronic stress in a sample of 73 patients with type 2 diabetes and 48 non-diabetic control participants, and to investigate associations with indicators of glycemic control (HbA1c), insulin resistance (HOMA-IR), β-cell functioning (C-peptide), illness duration, and the presence of microvascular complications. Chronic stress was measured using questionnaires [the Perceived Stress Scale (PSS), the Screening Scale of the Trier Inventory of Chronic Stress (SSCS), the Perceived Health Questionnaire (PHQ) as well as the Questionnaire on Stress in Patients with Diabetes-Revised (QSD-R)]; hair cortisol was used as a biological indicator.
RESULTS
We found that patients with type 2 diabetes had higher levels of hair cortisol in comparison to the control group ((1,112) = 5.3; = 0.023). Within the diabetic group, higher hair cortisol was associated with a longer duration of the illness ( = 0.25, = 0.04). General perceived stress did not show significant associations with metabolic outcomes in type 2 diabetes patients. In contrast, higher diabetes-related distress, as measured with the QSD-R, was associated with lower glycemic control ( = 0.28, = 0.02), higher insulin resistance ( = 0.26, = 0.03) and a longer duration of the illness ( = 0.30, = 0.01).
DISCUSSION
Our results corroborate the importance of chronic psychological stress in type 2 diabetes. It appears, however, that once type 2 diabetes has developed, diabetes-specific distress gains in importance over general subjective stress. On a biological level, increased cortisol production could be linked to the course of the illness.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Female; Hydrocortisone; Middle Aged; Stress, Psychological; Cross-Sectional Studies; Hair; Aged; Surveys and Questionnaires; Insulin Resistance; Adult; Glycated Hemoglobin; Risk Factors
PubMed: 38813430
DOI: 10.3389/fpubh.2024.1289689 -
Cardiovascular Diabetology May 2024Left ventricular global longitudinal strain (GLS) holds greater diagnostic and prognostic value than left ventricular ejection fraction (LVEF) in the heart failure (HF)...
BACKGROUND
Left ventricular global longitudinal strain (GLS) holds greater diagnostic and prognostic value than left ventricular ejection fraction (LVEF) in the heart failure (HF) patients. The triglyceride-glucose (TyG) index serves as a reliable surrogate for insulin resistance (IR) and is strongly associated with several adverse cardiovascular events. However, there remains a research gap concerning the correlation between the TyG index and GLS among patients with chronic heart failure (CHF).
METHOD
427 CHF patients were included in the final analysis. Patient demographic information, along with laboratory tests such as blood glucose, lipids profiles, and echocardiographic data were collected. The TyG index was calculated as Ln [fasting triglyceride (TG) (mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2].
RESULTS
Among CHF patients, GLS was notably lower in the higher TyG index group compared to the lower TyG index group. Following adjustment for confounding factors, GLS demonstrated gradual decrease with increasing TyG index, regardless of the LVEF level and CHF classification.
CONCLUSION
Elevated TyG index may be independently associated with more severe clinical left ventricular dysfunction in patients with CHF.
Topics: Humans; Heart Failure; Male; Female; Cross-Sectional Studies; Triglycerides; Middle Aged; Aged; Ventricular Function, Left; Blood Glucose; Chronic Disease; Ventricular Dysfunction, Left; Biomarkers; Stroke Volume; Predictive Value of Tests; Insulin Resistance; Prognosis; Global Longitudinal Strain
PubMed: 38811950
DOI: 10.1186/s12933-024-02259-2 -
Nature Communications May 2024Metabolic dysfunction-associated steatohepatitis (MASH) is the most prevalent cause of liver disease worldwide, with a single approved therapeutic. Previous research has...
Metabolic dysfunction-associated steatohepatitis (MASH) is the most prevalent cause of liver disease worldwide, with a single approved therapeutic. Previous research has shown that interleukin-22 (IL-22) can suppress β-cell stress, reduce local islet inflammation, restore appropriate insulin production, reverse hyperglycemia, and ameliorate insulin resistance in preclinical models of diabetes. In clinical trials long-acting forms of IL-22 have led to increased proliferation in the skin and intestine, where the IL-22RA1 receptor is highly expressed. To maximise beneficial effects whilst reducing the risk of epithelial proliferation and cancer, we designed short-acting IL-22-bispecific biologic drugs that successfully targeted the liver and pancreas. Here we show 10-fold lower doses of these bispecific biologics exceed the beneficial effects of native IL-22 in multiple preclinical models of MASH, without off-target effects. Treatment restores glycemic control, markedly reduces hepatic steatosis, inflammation, and fibrogenesis. These short-acting IL-22-bispecific targeted biologics are a promising new therapeutic approach for MASH.
Topics: Interleukin-22; Interleukins; Animals; Liver; Pancreas; Humans; Mice; Fatty Liver; Male; Mice, Inbred C57BL; Disease Models, Animal; Insulin Resistance; Receptors, Interleukin
PubMed: 38811532
DOI: 10.1038/s41467-024-48317-x -
PloS One 2024The association between Alzheimer's disease and metabolic disorders as significant risk factors is widely acknowledged. However, the intricate molecular mechanism...
The association between Alzheimer's disease and metabolic disorders as significant risk factors is widely acknowledged. However, the intricate molecular mechanism intertwining these conditions remains elusive. To address this knowledge gap, we conducted a thorough investigation using a bioinformatics method to illuminate the molecular connections and pathways that provide novel perspectives on these disorders' pathological and clinical features. Microarray datasets (GSE5281, GSE122063) from the Gene Expression Omnibus (GEO) database facilitated the way to identify genes with differential expression in Alzheimer's disease (141 genes). Leveraging CoreMine, CTD, and Gene Card databases, we extracted genes associated with metabolic conditions, including hypertension, non-alcoholic fatty liver disease, and diabetes. Subsequent analysis uncovered overlapping genes implicated in metabolic conditions and Alzheimer's disease, revealing shared molecular links. We utilized String and HIPPIE databases to visualize these shared genes' protein-protein interactions (PPI) and constructed a PPI network using Cytoscape and MCODE plugin. SPP1, CD44, IGF1, and FLT1 were identified as crucial molecules in the main cluster of Alzheimer's disease and metabolic syndrome. Enrichment analysis by the DAVID dataset was employed and highlighted the SPP1 as a novel target, with its receptor CD44 playing a significant role in the inflammatory cascade and disruption of insulin signaling, contributing to the neurodegenerative aspects of Alzheimer's disease. ECM-receptor interactions, focal adhesion, and the PI3K/Akt pathways may all mediate these effects. Additionally, we investigated potential medications by repurposing the molecular links using the DGIdb database, revealing Tacrolimus and Calcitonin as promising candidates, particularly since they possess binding sites on the SPP1 molecule. In conclusion, our study unveils crucial molecular bridges between metabolic syndrome and AD, providing insights into their pathophysiology for therapeutic interventions.
Topics: Alzheimer Disease; Humans; Metabolic Syndrome; Drug Repositioning; Protein Interaction Maps; Systems Biology; Gene Regulatory Networks; Computational Biology; Signal Transduction; Databases, Genetic; Gene Expression Profiling
PubMed: 38809924
DOI: 10.1371/journal.pone.0304410 -
Brazilian Journal of Medical and... 2024Accumulation of visceral adipose tissue is associated with metabolic syndrome (MS), insulin resistance, and dyslipidemia. Here we examined several morphometric and...
Accumulation of visceral adipose tissue is associated with metabolic syndrome (MS), insulin resistance, and dyslipidemia. Here we examined several morphometric and biochemical parameters linked to MS in a rodent litter size reduction model, and how a 30-day fish oil (FO) supplementation affected these parameters. On day 3 post-birth, pups were divided into groups of ten or three. On day 22, rats were split into control (C) and small litter (SL) until 60 days old. Then, after metabolic disturbance and obesity were confirmed, FO supplementation started for 30 days and the new groups were named control (C), FO supplemented (FO), obese (Ob), and obese FO supplemented (ObFO). Comparison was performed by Student t-test or 2-way ANOVA followed by Tukey post hoc test. At the end of the 60-day period, SL rats were hyperphagic, obese, hypoinsulinemic, normoglycemic, and had high visceral fat depot and high interleukin (IL)-6 plasma concentration. Obese rats at 90 days of age were fatter, hyperphagic, hyperglycemic, hypertriacylgliceromic, hipoinsulinemic, with low innate immune response. IL-6 production ex vivo was higher, but in plasma it was not different from the control group. FO supplementation brought all biochemical changes to normal values, normalized food intake, and reduced body weight and fat mass in obese rats. The innate immune response was improved but still not as efficient as in lean animals. Our results suggested that as soon MS appears, FO supplementation must be used to ameliorate the morpho- and biochemical effects caused by MS and improve the innate immune response.
Topics: Animals; Metabolic Syndrome; Fish Oils; Obesity; Dietary Supplements; Male; Rats, Wistar; Rats; Insulin Resistance; Intra-Abdominal Fat; Interleukin-6; Disease Models, Animal; Female
PubMed: 38808884
DOI: 10.1590/1414-431X2024e13172 -
BMC Endocrine Disorders May 2024Metabolic syndrome (MetS) is associated to sleep duration. It is crucial to identify factors that disrupt sleep regulation. The study aimed to assess the indirect effect...
BACKGROUND
Metabolic syndrome (MetS) is associated to sleep duration. It is crucial to identify factors that disrupt sleep regulation. The study aimed to assess the indirect effect of risk factors related to MetS severity through sleep duration by utilizing a structural equation model (SEM).
METHODS
The study involving 3,935 adults from the baseline data of the Ravansar Non-Communicable Disease (RaNCD) cohort study. MetS severity scores were the outcome variables. SEM was employed to explore the relationships, utilizing IBM SPSS and AMOS version 23.
RESULTS
The mean MetS severity score was higher in women compared to men (0.25 vs. 0.16, P = 0.003). In men, socioeconomic status (SES) has a positive direct effect (β = 0.048) and a negative indirect effect (β=-0.006) on MetS severity. Increased physical activity is directly (β=-0.036) and indirectly (β=-0.093) associated with reducing MetS severity. Nap duration is directly linked to an increase (β = 0.072) but has an indirect effect (β=-0.008) in decreasing MetS severity. In women, SES has a direct (β=-0.020) and indirect (β=-0.001) inverse relationship with MetS severity. Increased physical activity is directly (β=-0.048) and indirectly (β=-0.036) associated with decreasing MetS severity in women. Nap duration is directly associated with an increase in MetS severity (β=-0.018) but indirectly contributes to its reduction (β=-0.002). Sleep duration not only directly affects MetS severity but is also influenced by age, SES, physical activity, obesity and nap duration.
CONCLUSION
Physical activity, SES, and nap duration directly and indirectly effect the MetS severity. Sleep duration was recognized as a mediating variable that supports the indirect effects.
Topics: Humans; Metabolic Syndrome; Female; Male; Adult; Sleep; Severity of Illness Index; Middle Aged; Risk Factors; Latent Class Analysis; Cohort Studies; Exercise; Time Factors; Sleep Duration
PubMed: 38807076
DOI: 10.1186/s12902-024-01611-7 -
BMJ Open May 2024Adolescence is a sensitive period for cardiometabolic health. Yet, it remains unknown if adolescent health behaviours, such as alcohol use, smoking, diet and physical...
INTRODUCTION
Adolescence is a sensitive period for cardiometabolic health. Yet, it remains unknown if adolescent health behaviours, such as alcohol use, smoking, diet and physical activity, have differential effects across socioeconomic strata. Adopting a life-course perspective and a causal inference framework, we aim to assess whether the effects of adolescent health behaviours on adult cardiometabolic health differ by levels of neighbourhood deprivation, parental education and occupational class. Gaining a better understanding of these social disparities in susceptibility to health behaviours can inform policy initiatives that aim to improve population health and reduce socioeconomic inequalities in cardiometabolic health.
METHODS AND ANALYSIS
We will conduct a secondary analysis of the Young Finns Study, which is a longitudinal population-based cohort study. We will use measures of health behaviours-smoking, alcohol use, fruit and vegetable consumption, and physical activity-as exposure and parental education, occupational class and neighbourhood deprivation as effect modifiers during adolescence (ages 12-18 years). Eight biomarkers of cardiometabolic health (outcomes)-waist circumference, body mass index, blood pressure, low-density lipoprotein cholesterol, apolipoprotein B, plasma glucose and insulin resistance-will be measured when participants were aged 33-40. A descriptive analysis will investigate the clustering of health behaviours. Informed by this, we will conduct a causal analysis to estimate effects of single or clustered adolescent health behaviours on cardiometabolic health conditional on socioeconomic background. This analysis will be based on a causal model implemented via a directed acyclic graph and inverse probability-weighted marginal structural models to estimate effect modification.
ETHICS AND DISSEMINATION
The Young Finns study was conducted according to the guidelines of the Declaration of Helsinki, and the protocol was approved by ethics committees of University of Helsinki, Kuopio, Oulu, Tampere and Turku. We will disseminate findings at international conferences and a manuscript in an open-access peer-reviewed journal.
Topics: Humans; Adolescent; Health Behavior; Female; Adult; Male; Finland; Exercise; Longitudinal Studies; Child; Body Mass Index; Adolescent Behavior; Socioeconomic Factors; Smoking; Blood Pressure; Alcohol Drinking; Research Design; Waist Circumference; Cohort Studies; Blood Glucose; Diet; Insulin Resistance; Cardiovascular Diseases
PubMed: 38806419
DOI: 10.1136/bmjopen-2023-078428 -
PloS One 2024Attempts to subtype, type 2 diabetes (T2D) have mostly focused on newly diagnosed European patients. In this study, our aim was to subtype T2D in a non-white Emirati...
BACKGROUND
Attempts to subtype, type 2 diabetes (T2D) have mostly focused on newly diagnosed European patients. In this study, our aim was to subtype T2D in a non-white Emirati ethnic population with long-standing disease, using unsupervised soft clustering, based on etiological determinants.
METHODS
The Auto Cluster model in the IBM SPSS Modeler was used to cluster data from 348 Emirati patients with long-standing T2D. Five predictor variables (fasting blood glucose (FBG), fasting serum insulin (FSI), body mass index (BMI), hemoglobin A1c (HbA1c) and age at diagnosis) were used to determine the appropriate number of clusters and their clinical characteristics. Multinomial logistic regression was used to validate clustering results.
RESULTS
Five clusters were identified; the first four matched Ahlqvist et al subgroups: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and a fifth new subtype of mild early onset diabetes (MEOD). The Modeler algorithm allows for soft assignments, in which a data point can be assigned to multiple clusters with different probabilities. There were 151 patients (43%) with membership in cluster peaks with no overlap. The remaining 197 patients (57%) showed extensive overlap between clusters at the base of distributions.
CONCLUSIONS
Despite the complex picture of long-standing T2D with comorbidities and complications, our study demonstrates the feasibility of identifying subtypes and their underlying causes. While clustering provides valuable insights into the architecture of T2D subtypes, its application to individual patient management would remain limited due to overlapping characteristics. Therefore, integrating simplified, personalized metabolic profiles with clustering holds greater promise for guiding clinical decisions than subtyping alone.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Female; Middle Aged; Blood Glucose; Glycated Hemoglobin; Body Mass Index; Cluster Analysis; Adult; Aged; Insulin; Insulin Resistance; United Arab Emirates
PubMed: 38805513
DOI: 10.1371/journal.pone.0304036 -
PloS One 2024Type 2 diabetes mellitus is a disease in which insulin action is impaired, and an acute bout of strength exercise can improve insulin sensitivity. Current guidelines for...
The ASSIST trial: Acute effects of manipulating strength exercise volume on insulin sensitivity in obese adults: A protocol for a randomized controlled, crossover, clinical trial.
Type 2 diabetes mellitus is a disease in which insulin action is impaired, and an acute bout of strength exercise can improve insulin sensitivity. Current guidelines for strength exercise prescription suggest that 8 to 30 sets could be performed, although it is not known how variations in exercise volume impact insulin sensitivity. Additionally, this means an almost 4-fold difference in time commitment, which might directly impact an individual's motivation and perceived capacity to exercise. This study will assess the acute effects of high- and low-volume strength exercise sessions on insulin sensitivity. After being thoroughly familiarized, 14 obese individuals of both sexes (>40 year old) will undergo 3 random experimental sessions, with a minimum 4-day washout period between them: a high-volume session (7 exercises, 3 sets per exercise, 21 total sets); a low-volume session (7 exercises, 1 set per exercise, 7 total sets); and a control session, where no exercise will be performed. Psychological assessments (feeling, enjoyment, and self-efficacy) will be performed after the sessions. All sessions will be held at night, and the next morning, an oral glucose tolerance test will be performed in a local laboratory, from which indexes of insulin sensitivity will be derived. We believe this study will aid in strength exercise prescription for individuals who claim not to have time to exercise or who perceive high-volume strength exercise intimidating to adhere to. This trial was prospectively registered (ReBEC #RBR-3vj5dc5 https://ensaiosclinicos.gov.br/rg/RBR-3vj5dc5).
Topics: Adult; Female; Humans; Male; Middle Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Insulin Resistance; Obesity; Randomized Controlled Trials as Topic; Resistance Training
PubMed: 38805474
DOI: 10.1371/journal.pone.0302480