Fecal microbiota transplantation ameliorates high-fat diet-induced memory impairment in mice.

Gut dysbiosis is linked to metabolic and neurodegenerative diseases and comprises a plausible link between high-fat diet (HFD) and brain dysfunction. Here we show that gut microbiota modulation by either antibiotic treatment for 5 weeks or a brief 3-day fecal microbiota transplantation (FMT) regimen from low-fat (control) diet-fed mice decreased weight gain, adipose tissue hypertrophy, and glucose intolerance induced by HFD in C57BL/6 male mice. Notably, gut microbiota modulation by FMT completely reversed impaired recognition memory induced by HFD, whereas modulation by antibiotics had less pronounced effect. Improvement in recognition memory by FMT was accompanied by decreased HFD-induced astrogliosis in the hippocampal cornu ammonis region. Gut microbiome composition analysis indicated that HFD diminished microbiota diversity compared to control diet, whereas FMT partially restored the phyla diversity. Our findings reinforce the role of the gut microbiota on HFD-induced cognitive impairment and suggest that modulating the gut microbiota may be an effective strategy to prevent metabolic and cognitive dysfunction associated with unfavorable dietary patterns.

The patient's safety and access to experimental drugs after the termination of clinical trials: regulations and trends.

PURPOSE: Participants' rights and safety must be guaranteed not only while a clinical trial is being conducted but also when a clinical trial finishes. The criteria for post-trial access to experimental drugs, however, are unclear in various countries. The objectives of this study were (i) to ascertain if there were regulations or guidelines related to patients' access to drugs after the end of clinical trials in the countries selected in the study and (ii) to analyze trends in post-trial access in countries classified by their level of economic development. METHODS: This study is a retrospective review. The data are from the records of clinical trials from 2014 registered in the World Health Organization's International Clinical Trials Registry Platform (ICTRP) database. RESULTS: Among the countries selected, provision of drugs post-trial is mandatory only in Argentina, Brazil, Chile, Finland, and Peru. The plans for post-trial access tend to be more present in low- and middle-income and upper middle-income countries, in comparison with high-income countries. Studies involving vulnerable populations are 2.53 times more likely to have plans for post-trial access than studies which do not. CONCLUSIONS: The guaranteeing of post-trial access remains mandatory in few countries. Considering that individuals seen as vulnerable have been included in clinical trials without plans for post-trial access, stakeholders must discuss the need to develop regulations mandating the guaranteeing of post-trial access in specified situations.

Longer Telomere Length in Elite Master Sprinters: Relationship to Performance and Body Composition.

Emergent evidence suggests that the long-term healthy lifestyle of master athletes may attenuate aging. We compared telomere length (TL) of high-level master sprinters and non-athlete age-matched controls, and analyzed the relationships of TL with performance and body fat. Elite master sprinters (n=11; aged 50.1±9.2yrs) and healthy untrained controls (n=10; aged 45.4±10.9yrs) had blood samples collected for biochemical and biomolecular analyses. Master sprinters had longer TL, lower body fat and BMI, and a better lipid profile than age-matched controls (p<0.05). A large effect size was verified comparing TL between athletes vs. controls (Cohen's d=1.039), with a significant negative correlation between TL and performance decline per decade (r=-0.624, p<0.01) and a positive correlation of TL and actual performance level (r=0.641, p<0.01). In conclusion, TL of elite master sprinters was longer than their untrained peers, and seems to be not only a marker of health status, but also an indicator of sports longevity since both actual performance level and its decrease over years were related to TL. Further research might assess the TL of elite master endurance athletes for comparison with sprinters, and also investigate the underlying mechanisms by which the attenuation of telomere shortening occurs in master athletes.

Thermogenesis in white adipose tissue: An unfinished story about PPARγ.

BACKGROUND: Recruiting thermogenic adipocytes in white adipose tissue represents a potential therapeutic strategy for obesity. Interestingly, PPARγ, a major regulator of lipogenesis, is also a key factor in inducing thermogenic genes in adipose tissue. SCOPE OF THE REVIEW: We summarize some of the recent findings regarding the biology of beige adipocytes and their potential significance for metabolic health. We also discuss the role of PPARγ in development of beige adipocyte phenotype and in inducing two apparently divergent processes, namely, lipogenesis and thermogenesis. MAJOR CONCLUSIONS: PPARγ post-translation modifications and differential coregulator recruitment may be key factors in defining adipocyte commitment with lipogenesis or thermogenesis. GENERAL SIGNIFICANCE: Dissecting the mechanisms underlying its thermogenic effects may prompt the development of a new generation of PPARγ-based therapies.

Trends in research involving human beings in Brazil.

Developing countries have experienced a dramatic increase in the number of clinical studies in the last decades. The aim of this study was to describe 1) the number of clinical trials submitted to the Brazilian Health Surveillance Agency (Agência Nacional de Vigilância Sanitária, Anvisa) from 2007 to 2012 and the number of human-subject research projects approved by research ethics committees (RECs) and the National Research Ethics Committee (Comissão Nacional de Ética em Pesquisa, CONEP) in Brazil from 2007 to 2011 and 2) the diseases most frequently studied in Brazilian states in clinical trials approved in the country from 2009 to 2012, based on information from an Anvisa databank. Two databases were used: 1) the National Information System on Research Ethics Involving Human Beings (Sistema Nacional de Informação Sobre Ética em Pesquisa envolvendo Seres Humanos, SISNEP) and 2) Anvisa's Clinical Research Control System (Sistema de Controle de Pesquisa Clínica, SCPC). Data from the SCPC indicated an increase of 32.7% in the number of clinical trials submitted to Anvisa, and data from the SISNEP showed an increase of 69.9% in those approved by RECs and CONEP (from 18 160 in 2007 to 30 860 in 2011). Type 2 diabetes (26.0%) and breast cancer (20.5%)-related to the main causes of mortality in Brazil-were the two most frequently studied diseases. The so-called “neglected diseases,” such as dengue fever, were among the least studied diseases in approved clinical trials, despite their significant impact on social, economic, and health indicators in Brazil. Overall, the data indicated 1) a clear trend toward more research involving human beings in Brazil, 2) good correspondence between diseases most studied in clinical trials approved by Anvisa and the main causes of death in Brazil, and 3) a low level of attention to neglected diseases, an issue that should be considered in setting future research priorities, given their socioeconomic and health effects.

Body mass trajectory from diagnosis to the end of treatment in a pediatric acute lymphoblastic leukemia cohort.

The advances in pediatric acute lymphoblastic leukemia (ALL) care have substantially increased survival, and the late effects of treatment are a growing concern. Obesity development is frequent following ALL therapy and may significantly contribute to long-term morbidity and mortality. We examined the body mass trajectory of 208 children with ALL, from the diagnosis to the completion of therapy. We found that 7.2% of children were overweight or obese at diagnosis, which increased to 19.7% at the end of induction therapy and 20.8% after completion of treatment. In a multivariable linear regression model, age at ALL diagnosis, the type of chemotherapy regimen, and body mass index (BMI) z-score at diagnosis were significant predictors of BMI z-score after induction therapy, whereas BMI z-score at diagnosis was the only significant predictor of BMI z-score at the completion of treatment. In a subgroup of 120 children, we found no association between nutrition status at diagnosis and the risk of ALL relapse or poorer overall survival. Our findings indicate that weight gain occurs early during ALL therapy and is predicted by weight status at diagnosis. Therefore, nutritional status should be assessed throughout treatment, and weight management interventions should be considered early, particularly for patients with higher weight at diagnosis.

Early-life exposure to antibiotics and excess body weight in childhood and adolescence: A systematic review and meta-analysis.

BACKGROUND: The association between early-life exposure to antibiotics and overweight/obesity is unclear. We conducted a systematic review and meta-analysis to address this issue. METHODS: We searched PubMed, Web of Science, Scopus, and grey literature from inception to August 10, 2022, for cohort studies investigating the association between early-life exposure to antibiotics and weight outcomes. Two independent reviewers screened studies for eligibility, extracted data, assessed risk of bias, and examined the certainty of the evidence. Random-effects meta-analyses was used for pooling the data. The review was registered in PROSPERO, CRD42021265417. RESULTS: We included 42 studies and data from 28 of them were pooled in the quantitative synthesis. Overall antenatal (OR 1.10, 95% CI 1.04-1.16; 518,095 children, very low certainty) and second trimester (OR 1.11, 95% CI 1.08-1.14, 248,469 children, low certainty) exposure to antibiotics were associated with increased risk of overweight/obesity in childhood/adolescence. Overall early postnatal antibiotic exposure was also associated with increased likelihood of overweight/obesity in childhood/adolescence (OR 1.09, 95% CI 1.05-1.12, 1,488,316 children, very low certainty). The magnitude of the association increased from exposure to one (OR 1.07, 95% CI 1.00-1.15, 512,954 children) to four or more courses of antibiotics (OR 1.31, 95% CI 1.17-1.46, 543,627 children). CONCLUSION: Antenatal and early postnatal exposure to antibiotics is associated increased likelihood of overweight/obesity, although the findings are limited by the very low certainty of evidence. We highlight the need for homogeneous prospective studies addressing potential confounding factors to further explore the link between exposure to antibiotics and the risk of excess body weight.

Early-life exposure to endocrine-disrupting chemicals and autistic traits in childhood and adolescence: a systematic review of epidemiological studies.

Aims: Exposure to endocrine-disrupting chemicals (EDCs) during critical neurodevelopmental windows has been associated with the risk of autistic traits. This systematic review of epidemiological studies examined the association between maternal exposure to EDCs during pregnancy and the risk of autism spectrum disorder (ASD) in the offspring. Methods: We searched PubMed, Web of Science, Scopus, and Google Scholar from inception to November 17, 2022, for studies investigating the association between prenatal exposure to EDCs and outcomes related to ASD. Two independent reviewers screened studies for eligibility, extracted data, and assessed the risk of bias. The review was registered in PROSPERO (CRD42023389386). Results: We included 27 observational studies assessing prenatal exposure to phthalates (8 studies), polychlorinated biphenyls (8 studies), organophosphate pesticides (8 studies), phenols (7 studies), perfluoroalkyl substances (6 studies), organochlorine pesticides (5 studies), brominated flame retardants (3 studies), dioxins (1 study), and parabens (1 study). The number of examined children ranged from 77 to 1,556, the age at the assessment of autistic traits ranged from 3 to 14 years, and most studies assessed autistic traits using the Social Responsiveness Scale. All but one study was considered to have a low risk of bias. Overall, there was no association between maternal exposure to specific ECDs during pregnancy and the occurrence of autistic traits in offspring. Conclusions: Findings from the epidemiological studies evaluated here do not support an association between prenatal exposure to ECDs and the likelihood of autistic traits in later in life. These findings should not be interpreted as definitive evidence of the absence of neurodevelopment effects of EDCs affecting ASD risk, given the limitations of current studies such as representative exposure assessment, small sample sizes, inadequacy to assess sexually dimorphic effects, or the effects of EDC mixtures. Future studies should carefully address these limitations.

The effect of long-term exposure to nonylphenol at environmentally relevant levels on mouse liver and adipose tissue.

Exposure to the xenoestrogen nonylphenol (NP) during critical windows of development leads to metabolic abnormalities in adult life. However, less is known about NP exposure outside the developmental period on metabolic outcomes. We investigated the effect of prolonged exposure to NP after sexual maturity and at environmentally relevant concentrations below the 'no observable adverse effects level' (0.5 and 2.5 mg/kg/d). Male Swiss mice fed a normal-fat diet exposed to 2.5 mg/kg/d NP showed reduced weight gain and hepatic fat content. In male and female C57BL/6 mice fed a high-fat diet, NP exposure modified the mRNA levels of estrogen receptor α (Esr1) and adipose lineage markers in a sexually dimorphic and adipose depot-dependent pattern. Moreover, in primary female but not male stromal vascular cells from C57BL/6 mouse inguinal WAT induced to differentiate into adipocytes, NP upregulated Fabp4 expression. Low-level exposure to NP outside critical developmental windows may affect the metabolic phenotype distinctly. DATA AVAILABILITY STATEMENT: All data not included in the manuscript, such as raw results, are available upon request and should be addressed to AAA.

Unplanned pregnancy in Brazil: national study in eight university hospitals.

OBJECTIVE: To estimate the prevalence of unplanned pregnancy in eight public university hospitals, distributed in the five regions that make up Brazil. METHODS: A secondary analysis of a national multicenter cross-sectional study, carried out in eight public university hospitals between June 1 and August 31, 2020, in Brazil. Convenience sample including women who gave birth within sixty consecutive days and met the following criteria: over 18 years old; gestational age over 36 weeks at delivery; with a single and live newborn, without malformations. RESULTS: Sample composed of 1,120 postpartum women, of whom 756 (67.5%) declared that the pregnancy had not been planned. The median prevalence of unplanned pregnancy was 59.7%. The prevalence of unplanned pregnancy across hospitals differed significantly: Campinas (54.8%), Porto Alegre (58.2%), Florianópolis (59%), Teresina (61.2%), Brasília (64.3%), São Paulo (64.6%), Campo Grande (73.9%) and Manaus (95.3%) (p < 0.001). Factors significantly associated with unplanned pregnancy were maternal age, black color, lower family income, greater number of children, greater number of people living in household, and not having a partner. CONCLUSION: In the studied sample, about two thirds of the pregnancies were declared as unplanned. The prevalence of unplanned pregnancies was related to social and demographic factors and varied significantly across the university hospitals evaluated.

Early-life metabolic dysfunction impairs cognition and mitochondrial function in mice.

The impact of overnutrition early in life is not restricted to the onset of cardiovascular and metabolic diseases, but also affects critical brain functions related to cognition. This study aimed to evaluate the relationship between peripheral metabolic and bioenergetic changes induced by a two-hit protocol and their impact on cognitive function in juvenile mice. Three-week-old male C57BL/6 mice received a high-fat diet (HFD) or control diet for 7 weeks, associated with two low doses of streptozotocin (STZ) or vehicle. Despite the absence of obesity, HFD+STZ impaired glucose metabolism and induced a trend towards cholesterol increase. The two-hit protocol impaired recognition and spatial memories in juvenile mice, without inducing a depressive-like behavior. HFD+STZ mice presented increased immunoreactivity for GFAP and a trend towards a decrease in NeuN in the hippocampus. The treatment caused a bioenergetic impairment in the hippocampus, characterized by a decrease in both O2 consumption related to ATP production and in the maximum respiratory capacity. The thermogenic capacity of brown adipose tissue was impaired by the two-hit protocol, here verified through the absence of a decrease in O2 consumption after uncoupled protein-1 inhibition and an increase in the reserve respiratory capacity. Impaired mitochondrial function was also observed in the liver of HFD+STZ juvenile mice, but not in their heart. These results indicate that exposure to HFD+STZ early in life has a detrimental impact on the bioenergetic and mitochondrial function of tissues with metabolic and thermogenic activities, which is likely related to hippocampal metabolic changes and cognitive impairment.

Thermogenic adipose tissue aging: Mechanisms and implications.

Adipose tissue undergoes significant anatomical and functional changes with aging, leading to an increased risk of metabolic diseases. Age-related changes in adipose tissue include overall defective adipogenesis, dysfunctional adipokine secretion, inflammation, and impaired ability to produce heat by nonshivering thermogenesis. Thermogenesis in adipose tissue is accomplished by brown and beige adipocytes, which also play a role in regulating energy homeostasis. Brown adipocytes develop prenatally, are found in dedicated depots, and involute in early infancy in humans. In contrast, beige adipocytes arise postnatally in white adipose tissue and persist throughout life, despite being lost with aging. In recent years, there have been significant advances in the understanding of age-related reduction in thermogenic adipocyte mass and function. Mechanisms underlying such changes are beginning to be delineated. They comprise diminished adipose precursor cell pool size and adipogenic potential, mitochondrial dysfunction, decreased sympathetic signaling, and altered paracrine and endocrine signals. This review presents current evidence from animal models and human studies for the mechanisms underlying thermogenic adipocyte loss and discusses potential strategies targeting brown and beige adipocytes to increase health span and longevity.

The association between excess body weight at diagnosis and pediatric leukemia prognosis: A systematic review and meta-analysis.

Obesity affects the prognosis of several types of cancer. However, whether excess body weight is independently associated with adverse outcomes following initial pediatric acute leukemia (AL) treatment is still unclear. We conducted a systematic review and meta-analysis to investigate the impact of overweight/obesity at diagnosis on pediatric AL prognosis following initial treatment by performing an extensive database search up to January 22, 2021. Twenty-three studies were included, providing data for 15689 children with acute lymphoblastic leukemia (ALL) and 2506 children with acute myeloid leukemia (AML). Data from 12 studies were pooled in the meta-analysis. Children with overweight/obesity at diagnosis of ALL had poorer event free-survival (random-effects hazard ratio of 1.44, 95%CI 1.16-1.79, p = 0.0008), but no difference in overall survival (random-effects hazard ratio 1.33, 95%CI 0.77-2.29, p = 0.31) when compared with healthy-weight children. Children with overweight/obesity at diagnosis of AML had no difference in event-free survival (random-effects hazard ratio of 0.88, 95%CI 0.48-1.59, p = 0.66) or overall survival (random-effects hazard ratio 1.40, 95%CI 0.78-2.49, p = 0.26), when compared with healthy-weight children. This systematic review and meta-analysis indicates that overweight/obesity negatively affects the prognosis of children with ALL. Future studies should address the best approach to consider nutritional status in their management.

Obesity and endocrine-disrupting chemicals.

Obesity is now a worldwide pandemic. The usual explanation given for the prevalence of obesity is that it results from consumption of a calorie dense diet coupled with physical inactivity. However, this model inadequately explains rising obesity in adults and in children over the past few decades, indicating that other factors must be important contributors. An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture that interferes with any aspect of hormone action. EDCs have become pervasive in our environment, allowing humans to be exposed daily through ingestion, inhalation, and direct dermal contact. Exposure to EDCs has been causally linked with obesity in model organisms and associated with obesity occurrence in humans. Obesogens promote adipogenesis and obesity, in vivo, by a variety of mechanisms. The environmental obesogen model holds that exposure to obesogens elicits a predisposition to obesity and that such exposures may be an important yet overlooked factor in the obesity pandemic. Effects produced by EDCs and obesogen exposure may be passed to subsequent, unexposed generations. This "generational toxicology" is not currently factored into risk assessment by regulators but may be another important factor in the obesity pandemic as well as in the worldwide increases in the incidence of noncommunicable diseases that plague populations everywhere. This review addresses the current evidence on how obesogens affect body mass, discusses long-known chemicals that have been more recently identified as obesogens, and how the accumulated knowledge can help identify EDCs hazards.

Exposure to endocrine disruptors and risk of breast cancer: A systematic review.

AIM: The aim of this study was to investigate the association between human exposure to endocrine disruptors (EDs) and the risk of breast cancer. METHODS: This was a systematic review conducted by searching Cochrane Library, LILACS, Livivo, PubMed, and Science Direct. Observational studies addressing the association between exposure to EDs and breast cancer risk in adults were included. Risk of bias was assessed using the National Toxicology Program's Office of Health Assessment Translation tool. RESULTS: a total of 37 studies were included. Most studies reported that exposure to organochlorine pesticides, phthalates, heavy metals, and polycyclic aromatic hydrocarbons was associated with increased breast cancer risk. CONCLUSION: qualitative analysis of observational studies indicates that human exposure to EDs is associated with increased breast cancer risk. Additional studies are needed to determine whether this association is causal.

Coffee Increases Post-Exercise Muscle Glycogen Recovery in Endurance Athletes: A Randomized Clinical Trial.

Coffee is one of the most widely consumed beverages worldwide and caffeine is known to improve performance in physical exercise. Some substances in coffee have a positive effect on glucose metabolism and are promising for post-exercise muscle glycogen recovery. We investigated the effect of a coffee beverage after exhaustive exercise on muscle glycogen resynthesis, glycogen synthase activity and glycemic and insulinemic response in a double-blind, crossover, randomized clinical trial. Fourteen endurance-trained men performed an exhaustive cycle ergometer exercise to deplete muscle glycogen. The following morning, participants completed a second cycling protocol followed by a 4-h recovery, during which they received either test beverage (coffee + milk) or control (milk) and a breakfast meal, with a simple randomization. Blood samples and muscle biopsies were collected at the beginning and by the end of recovery. Eleven participants were included in data analysis (age: 39.0 ± 6.0 years; BMI: 24.0 ± 2.3 kg/m2; VO2max: 59.9 ± 8.3 mL·kg-1·min-1; PPO: 346 ± 39 W). The consumption of coffee + milk resulted in greater muscle glycogen recovery (102.56 ± 18.75 vs. 40.54 ± 18.74 mmol·kg dw-1; p = 0.01; d = 0.94) and greater glucose (p = 0.02; d = 0.83) and insulin (p = 0.03; d = 0.76) total area under the curve compared with control. The addition of coffee to a beverage with adequate amounts of carbohydrates increased muscle glycogen resynthesis and the glycemic and insulinemic response during the 4-h recovery after exhaustive cycling exercise.

Synthesis and anti-inflammatory activity of new arylidene-thiazolidine-2,4-diones as PPARgamma ligands.

Eight new 5-arylidene-3-benzyl-thiazolidine-2,4-diones with halide groups on their benzyl rings were synthesized and assayed in vivo to investigate their anti-inflammatory activities. These compounds showed considerable biological efficacy when compared to rosiglitazone, a potent and well-known agonist of PPARgamma, which was used as a reference drug. This suggests that the substituted 5-arylidene and 3-benzylidene groups play important roles in the anti-inflammatory properties of this class of compounds. Docking studies with these compounds indicated that they exhibit specific interactions with key residues located in the site of the PPARgamma structure, which corroborates the hypothesis that these molecules are potential ligands of PPARgamma. In addition, competition binding assays showed that four of these compounds bound directly to the ligand-binding domain of PPARgamma, with reduced affinity when compared to rosiglitazone. An important trend was observed between the docking scores and the anti-inflammatory activities of this set of molecules. The analysis of the docking results, which takes into account the hydrophilic and hydrophobic interactions between the ligands and the target, explained why the 3-(2-bromo-benzyl)-5-(4-methanesulfonyl-benzylidene)-thiazolidine-2,4-dione compound had the best activity and the best docking score. Almost all of the stronger hydrophilic interactions occurred between the substituted 5-arylidene group of this compound and the residues of the binding site.

Factors associated with overweight and abdominal obesity in Brazilian school-aged children: a comprehensive approach.

Objective We investigated the association between demographic, socio-economic, perinatal, parental and lifestyle-related factors with general and abdominal obesity among prepubertal children aged 6 to 8 years in a Southeastern city of Brazil. Subjects and methods A total of 486 children were randomly selected from public schools in the city of Patos de Minas, and examined to determine body mass index (BMI) and waist circumference (WC). Demographic, socio-economic, perinatal, parental and lifestyle-related data were obtained and assessed as independent risk factors for overweight/obesity and abdominal obesity, using multiple regression analysis. Results Obesity/overweight (BMI percentile ≥ 85), seen in 19% of the children, was positively associated with low maternal education, being born small for gestational age, maternal BMI and screen time, whereas abdominal obesity (WC percentile > 90), seen in 9.9% of the children, was positively associated with maternal age and maternal BMI. When BMI and WC percentile were analyzed as continuous variables, birth by cesarean section, parental BMI, and lower sleep time were positively associated with BMI percentile, and birth by cesarean section, being born small for gestational age, and parental BMI were positively associated with WC percentile. Conclusion Our findings suggest that the frequency of overweight and obesity in a city in the Southeastern region of Brazil is similar to the global frequency reported by the World Health Organization. We also found that many modifiable risk factors were associated with general and abdominal obesity, and these may possibly substantiate future strategies to prevent childhood obesity and its consequences in adult life.

Predictors of sudomotor dysfunction in patients with type 1 diabetes without clinical evidence of peripheral neuropathy.

AIM: To investigate the frequency of foot sudomotor dysfunction determined by the electrochemical skin conductance test (ESC) and its independent predictors in individuals with type 1 diabetes mellitus (T1D) and no clinical evidence of diabetic peripheral neuropathy (DPN). METHODS: Adults with T1D for longer than 5 years and without DPN defined by the Michigan Neuropathy Screening Instrument and Neuropathy Disability Score were assessed for foot sudomotor dysfunction by ESC. Multivariate logistic regression analysis was used to examine the association between foot sudomotor dysfunction (ESC < 70 µS) and demographic, clinical, and biochemical variables. RESULTS: A total of 61 individuals with T1D were included. Their mean age was 29.5 ± 8.6 years, and mean diabetes duration was 17.8 ± 7.9 years. Foot sudomotor dysfunction was present in 16 (26.2%) participants, despite no clinical evidence of DPN. Retinopathy, hand sudomotor dysfunction and glycated haemoglobin (HbA1c) levels were identified as independent predictors of foot sudomotor dysfunction by multivariate logistic regression analysis. Retinopathy, hand sudomotor dysfunction, and every 1% increase of HbA1c increased the odds of foot sudomotor dysfunction by 2.48, 2.82, and 1.24-fold, respectively. CONCLUSION: Our findings indicate a high frequency of foot sudomotor dysfunction among individuals with T1D and no overt DPN. Factors associated with DPN, including retinopathy and higher HbA1c levels, independently predicted the occurrence of sudomotor dysfunction, suggesting that ESC assessment is a useful tool in the clinical setting to identify early small-fiber neuropathy.