Publications by authors named "Paolo Piaggi"

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.

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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.

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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).

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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.

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Context: 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.

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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.

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Background: 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.

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The 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.

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Background: 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.

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Article Synopsis
  • * Researchers used metabolic chamber experiments and metabolite profiling to analyze substrate oxidation rates and energy expenditure across various diets, including fasting and high-fat diets.
  • * Findings reveal that diets promoting fat oxidation are linked to specific changes in metabolic pathways and metabolites, demonstrating the relationship between substrate availability and human physiology.
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  • The study investigates rare genetic variations linked to monogenic obesity in a community where polygenic obesity is more common, using whole-exome sequencing from over 6,800 people.
  • Researchers analyzed data from children and adults with extreme Body Mass Index (BMI) to identify nonsynonymous variants in 15 obesity-related genes.
  • Eight missense variants were found in six genes, with some variants (particularly in MC4R) already known to impair its function, while additional variants in KSR2 and NTRK2 are suggested to affect protein function and may contribute to severe obesity.
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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.

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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.

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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).

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Introduction: 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.

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Objective: 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.

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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.

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Article Synopsis
  • The study highlights that in mice, nearly 40% of the light phase and 80% of the dark phase are marked by periods of increased energy expenditure (EE), known as ultradian bouts.
  • These bouts are associated with higher body temperatures and consist of most physical activity and wakefulness, suggesting that they are more indicative of mouse physiology than the traditional light/dark cycles.
  • The findings indicate that these ultradian bouts, resulting from brain-driven increases in body temperature, lead to significant energy expenditure from various bodily activities, making mouse metabolic physiology largely episodic rather than solely reliant on circadian rhythms.
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Objective: 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.

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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.

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Aim: 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.

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Article Synopsis
  • The study aimed to investigate how weight loss affects the size of adipocytes (fat cells) and the caloric density of adipose tissue in healthy adults undergoing caloric restriction for six weeks.
  • Results showed that large adipocyte sizes decreased significantly with weight loss, and these reductions were correlated with the loss of fat mass and decrease in waist circumference.
  • Despite the changes in large cell diameters, the overall caloric density of adipose tissue did not change, highlighting that larger fat cells may be important targets for weight loss efforts.
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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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