Aim: Whether markers of acid accumulation [decreased plasma bicarbonate, increased anion gap (AG) and corrected anion gap (CAG)] are associated with insulin sensitivity and alter diabetes risk is unclear. We aimed to examine the association of these markers with the gold-standard measure of insulin sensitivity and incident type 2 diabetes.
Materials And Methods: Healthy adults without diabetes enrolled in a longitudinal study had baseline measures of acidosis (bicarbonate, AG, CAG), insulin sensitivity by hyperinsulinaemic-euglycaemic clamp, and body composition.
Objective: At present, total thyroidectomy and central neck dissection are the surgical approaches recommended for the initial treatment of medullary thyroid cancer (MTC) independently of the size, number of tumor foci, age of patients, and other demographic and clinico-pathological parameters. The aims of the present study were to assess the prevalence of multifocality in hereditary (hMTC) and sporadic (sMTC) patients and to correlate the presence of multifocality with clinico-pathological parameters to provide a proof of concept that lobectomy can be safely performed in selected cases.
Methods: We analyzed the epidemiological, pathological, and clinical data of 389 MTC (311 sMTC and 78 hMTC) diagnosed in our center from 2005 to 2018.
Objective: To identify metabolic signatures of insulin action/secretion in Indigenous Americans (IAs) and their association with diabetes.
Research Design And Methods: We defined circulating metabolomic signatures of insulin action/secretion in 446 IAs, including glucose disposal rate during low-dose insulin clamp (Mlow) and endogenous glucose production (EGP) during insulin infusion (suppression of hepatic glucose production). We then determined associations of these metabolic scores with glucose tolerance (in a separate set of ∼700 IAs) and diabetes/metabolic risk in ∼2,000 individuals (from Coronary Artery Risk Development in Young Adults [CARDIA] study).
Background: Protein oxidation (PROTOX) typically accounts for the smallest fraction of daily energy expenditure (24hEE) in humans compared to carbohydrate and lipid oxidation. However, inter-individual differences in PROTOX may explain differences in fuel partitioning and body weight change. We aimed to elucidate the physiological determinants of PROTOX under controlled 24-h dietary conditions, including eucaloric feeding, fasting, and overfeeding diets with variable protein content.
View Article and Find Full Text PDFContext: Very-low-calorie ketogenic diet (VLCKD) is used for weight loss and management of obesity-related comorbidities.
Objective: We aimed at evaluating the effects of VLCKD on body composition and energy metabolism.
Methods: This prospective outpatient study included 17 women with obesity (mean age 41.
Am J Physiol Endocrinol Metab
April 2025
Leptin is a hormone produced by adipocytes that plays a crucial role in regulating energy homeostasis and body mass. Despite its close correlation with body fat, up to ∼40% of variation in plasma leptin concentration remains unexplained, allowing for the classification of a distinct "leptin phenotype." This leptin phenotype-characterized by either relatively high or relatively low leptin concentration relative to an individual's level of body fat-presents an intriguing opportunity to test whether relatively higher (compared with lower) leptin concentrations differentially affect energy expenditure, metabolic adaptation, and susceptibility to weight change in response to energy balance perturbations.
View Article and Find Full Text PDFBackground: The cerebellum is one of the major central nervous structures consistently altered in obesity. Its role in higher cognitive function, parts of which are affected by obesity, is mediated through projections to and from the cerebral cortex. We therefore investigated the relationship between body mass index (BMI) and cerebellocerebral connectivity.
View Article and Find Full Text PDFThe international medullary thyroid carcinoma (MTC) grading system (IMTCGS) has been proposed as an independent tool to predict disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS). We aimed to evaluate the performance of IMTCGS in our series of sporadic MTCs and to compare its predictive power with conventional prognostic factors. In a retrospective cohort study, we evaluated data from 314 patients with sporadic MTC, all managed at the Pisa University Hospital.
View Article and Find Full Text PDFBackground: Measures of energy metabolism (energy expenditure [EE], respiratory exchange ratio [RER]) have been associated with ad libitum energy intake (EI) and weight gain in previous observational studies, suggesting that energy-sensing mechanisms drive EI to meet metabolic energy demands.
Objectives: We aimed to employ mild cold exposure as an intervention to alter energy metabolism and evaluate its causal effects on concurrent and next day ad libitum EI.
Methods: In a controlled crossover study, 47 volunteers (16 female; age 37.
JCI Insight
November 2024
Obesity (Silver Spring)
September 2024
J Clin Endocrinol Metab
February 2025
Context: The active surveillance (AS) program for papillary thyroid carcinoma (≤1 cm) at low risk (mPTC) showed a low percentage of progression.
Objective: The aim of this study was to find a molecular signature of cases that showed disease progression during AS, which would allow their early identification.
Methods: We performed next-generation sequencing of 95 fine-needle aspiration cytology specimens from cases prospectively enrolled in the AS program to analyze key somatic driver alterations or gene fusions implicated in PTC tumorigenesis.
J Clin Endocrinol Metab
January 2025
Context: The locus CELSR2-PSRC1-SORT1, a primary genetic signal for lipids, has recently been implicated in different metabolic processes. Our investigation identified its association with energy metabolism.
Objective: This work aimed to determine biological mechanisms that govern diverse functions of this locus.
Physical activity (PA) is an important predictor of physical and mental health preventing chronic degenerative diseases. The purpose of this study was to investigate in a group of Italian high school students whether health-related quality of life (HRQoL) and lifestyle habits (diet) are associated with the level of physical activity performed (low, moderate, high). Data were collected from 2819 adolescents (n = 951 males).
View Article and Find Full Text PDFIntroduction: Historically, secular and seasonal trend analyses have been examined using self-report measures of intake. Rarely are objective measures and known determinants of dietary intake used in these analyses. Our objective was to quantify the seasonal and secular differences in an objective intake paradigm while considering the contribution of determinants, such as fat-free mass (FFM) index and spontaneous physical activity (SPA) limited to the restricted space of a whole-room calorimeter.
View Article and Find Full Text PDFObjective: The objective of this study was to study how acid accumulation (lower plasma bicarbonate and higher anion gap [AG] and corrected anion gap [CAG]) correlates with metabolic parameters, food intake, and 24-h energy expenditure (EE).
Methods: Acid accumulation was measured in 286 healthy adults with estimated glomerular filtration rate > 60 mL/min/1.73 m.
Genetic determinants of interindividual differences in energy expenditure (EE) are largely unknown. Sphingolipids, such as ceramides, have been implicated in the regulation of human EE via mitochondrial uncoupling. In this study, we investigated whether genetic variants within enzymes involved in sphingolipid synthesis and degradation affect EE and insulin-related traits in a cohort of American Indians informative for 24-h EE and glucose disposal rates during a hyperinsulinemic-euglycemic clamp.
View Article and Find Full Text PDFObjective: We investigated how changes in 24-h respiratory exchange ratio (RER) and substrate oxidation during fasting versus an energy balance condition influence subsequent ad libitum food intake.
Methods: Forty-four healthy, weight-stable volunteers (30 male and 14 female; mean [SD], age 39.3 [11.
The emerging field of precision nutrition is based on the notion that inter-individual responses across diets of different calorie-macronutrient content may contribute to inter-individual differences in metabolism, adiposity, and weight gain. Free-living diet studies have been traditionally challenged by difficulties in controlling adherence to prescribed calories and macronutrient content and rarely allow a period of metabolic stability prior to metabolic measures (to minimize influences of weight changes). In this context, key physiologic measures central to precision nutrition responses may be most precisely quantified via whole room indirect calorimetry over 24-h, in which precise control of activity and nutrition can be achieved.
View Article and Find Full Text PDFAim: Reduced renal insulin signalling is implicated in the pathogenesis of albuminuria. We sought to investigate whether insulin action and secretion, measured before diabetes onset, are associated with the development of albuminuria after diabetes onset.
Materials And Methods: Baseline body composition, insulin sensitivity by hyperinsulinaemic-euglycaemic clamp at submaximal and maximal insulin stimulation (240 and 2400 pmol/m/min; M-low and M-high), and insulin secretion by intravenous glucose tolerance test [acute insulin response (AIR)] were measured in 170 Southwestern Indigenous American adults who subsequently developed diabetes.
Introduction: Adolescents experience rapid physical, cognitive, and psychosocial growth with different factors contributing to health and well-being. In this view, an important role is played by body weight and related perceptions. The purpose was to determine, in a sample of Italian high school students, whether health-related quality of life (HRQoL) is associated with the different weight status categories (underweight, normal weight, overweight, obese), even considering sex differences.
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