[Impact of obesity and diabetes on health and cardiovascular disease]. / Impacto de la obesidad y la diabetes en la salud y en la enfermedad cardiovascular.

Obesity and type 2 diabetes mellitus (T2D) significantly increase the risk of cardiovascular diseases such as coronary artery disease, atrial fibrillation, heart failure, and sudden cardiac death. This risk is proportional to body mass index (BMI), is exacerbated by comorbidities such as hypertension and dyslipidemia, and includes emerging risk factors like insulin resistance, low-grade chronic inflammation, and thrombosis tendency. The distribution of adipose tissue, especially visceral fat and ectopic deposition in the heart, is another key factor in the development of cardiovascular diseases in these patients, along with atrial and ventricular remodeling. Bariatric surgery has been shown to be effective in reducing these risks. The prevention and treatment of cardiovascular diseases in obesity and T2D include lifestyle changes, specific pharmacological treatment and management of comorbidities, and attention to cardiovascular risk factors.

AI-based abdominal CT measurements of orthotopic and ectopic fat predict mortality and cardiometabolic disease risk in adults.

OBJECTIVES: To evaluate the utility of CT-based abdominal fat measures for predicting the risk of death and cardiometabolic disease in an asymptomatic adult screening population. METHODS: Fully automated AI tools quantifying abdominal adipose tissue (L3 level visceral [VAT] and subcutaneous [SAT] fat area, visceral-to-subcutaneous fat ratio [VSR], VAT attenuation), muscle attenuation (L3 level), and liver attenuation were applied to non-contrast CT scans in asymptomatic adults undergoing CT colonography (CTC). Longitudinal follow-up documented subsequent deaths, cardiovascular events, and diabetes. ROC and time-to-event analyses were performed to generate AUCs and hazard ratios (HR) binned by octile. RESULTS: A total of 9223 adults (mean age, 57 years; 4071:5152 M:F) underwent screening CTC from April 2004 to December 2016. 549 patients died on follow-up (median, nine years). Fat measures outperformed BMI for predicting mortality risk-5-year AUCs for muscle attenuation, VSR, and BMI were 0.721, 0.661, and 0.499, respectively. Higher visceral, muscle, and liver fat were associated with increased mortality risk-VSR > 1.53, HR = 3.1; muscle attenuation < 15 HU, HR = 5.4; liver attenuation < 45 HU, HR = 2.3. Higher VAT area and VSR were associated with increased cardiovascular event and diabetes risk-VSR > 1.59, HR = 2.6 for cardiovascular event; VAT area > 291 cm2, HR = 6.3 for diabetes (p < 0.001). A U-shaped association was observed for SAT with a higher risk of death for very low and very high SAT. CONCLUSION: Fully automated CT-based measures of abdominal fat are predictive of mortality and cardiometabolic disease risk in asymptomatic adults and uncover trends that are not reflected in anthropomorphic measures. CLINICAL RELEVANCE STATEMENT: Fully automated CT-based measures of abdominal fat soundly outperform anthropometric measures for mortality and cardiometabolic risk prediction in asymptomatic patients. KEY POINTS: Abdominal fat depots associated with metabolic dysregulation and cardiovascular disease can be derived from abdominal CT. Fully automated AI body composition tools can measure factors associated with increased mortality and cardiometabolic risk. CT-based abdominal fat measures uncover trends in mortality and cardiometabolic risk not captured by BMI in asymptomatic outpatients.

Effects of 1,144 km of road cycling performed in 7 days: a cardiometabolic imaging study.

This cardiometabolic imaging study was designed to document the adaptation of middle-aged recreational cyclists to a large exercise prescription not aiming at weight loss. Eleven middle-aged recreational male cyclists traveled 1,144 km over seven consecutive days. A comprehensive cardiometabolic profile including visceral and ectopic adiposity assessed by magnetic resonance imaging was obtained at baseline and following the exercise week. Cardiorespiratory fitness (CRF) was measured using maximal cardiopulmonary exercise testing. During the week, heart rate was monitored to calculate individual energy expenditure. Baseline characteristics of cyclists were compared to 86 healthy males with the same age range. Cyclists presented higher baseline CRF (+9.2 mL/kg/min, p<0.0001) and lower subcutaneous (-56.2 mL, p<0.05) and liver fat (-3.3%, p<0.05) compared to the reference group. Despite the large energy expenditure during the cycling week, the increase in energy intake limited decreases in body weight (-0.8±0.9 kg, p<0.05) and body mass index (-0.3±0.3 kg/m2, p<0.05). Loss of fat mass (-1.5±1.0 kg, p<0.001) and a trend toward an increased lean mass (+0.8±1.2 kg, p<0.07) were observed. Visceral adiposity (-14.1±14.2 mL, p<0.01) and waist circumference (-3.2±1.7 cm, p<0.0001) decreased while subcutaneous (-2.7±5.1 mL, NS), liver (-0.5±0.9%, NS) and cardiac fat (-0.3±2.3 mL, NS) remained unchanged. This cardiometabolic imaging study documents middle-aged recreational cyclists' subcutaneous and visceral adiposity as well as cardiac and liver fat responses to a large volume of endurance exercise despite an increase in energy intake aimed at limiting weight loss.

Overnutrition, Hyperinsulinemia and Ectopic Fat: It Is Time for A Paradigm Shift in the Management of Type 2 Diabetes.

The worldwide incidence of prediabetes/type 2 has continued to rise the last 40 years. In the same period, the mean daily energy intake has increased, and the quality of food has significantly changed. The chronic exposure of pancreatic ß-cells to calorie excess (excessive energy intake) and food additives may increase pancreatic insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing chronic hyperinsulinemia and peripheral insulin resistance. Chronic calorie excess and hyperinsulinemia may promote lipogenesis, inhibit lipolysis and increase lipid storage in adipocytes. In addition, calorie excess and hyperinsulinemia can induce insulin resistance and contribute to progressive and excessive ectopic fat accumulation in the liver and pancreas by the conversion of excess calories into fat. The personal fat threshold hypothesis proposes that in susceptible individuals, excessive ectopic fat accumulation may eventually lead to hepatic insulin receptor resistance, the loss of pancreatic insulin secretion, hyperglycemia and the development of frank type 2 diabetes. Thus, type 2 diabetes seems (partly) to be caused by hyperinsulinemia-induced excess ectopic fat accumulation in the liver and pancreas. Increasing evidence further shows that interventions (hypocaloric diet and/or bariatric surgery), which remove ectopic fat in the liver and pancreas by introducing a negative energy balance, can normalize insulin secretion and glucose tolerance and induce the sustained biochemical remission of type 2 diabetes. This pathophysiological insight may have major implications and may cause a paradigm shift in the management of type 2 diabetes: avoiding/reducing ectopic fat accumulation in the liver and pancreas may both be essential to prevent and cure type 2 diabetes.

Breast adiposity: Menopausal status impact and its influence on glycemic and anthropometric metabolic parameters.

CONTEXT: Ectopic fat depots are related to the deregulation of energy homeostasis, leading to diseases related to obesity and metabolic syndrome (MS). Despite significant changes in body composition over women's lifespan, little is known about the role of breast adipose tissue (BrAT) and its possible utilization as an ectopic fat depot in women of different menopausal statuses. OBJECTIVE: We aimed to assess the relationship between BrAT and metabolic glycemic and lipid profiles and body composition parameters in adult women. METHODS: In this cross-sectional study, we enrolled adult women undergoing routine mammograms to perform history and physical examination, body composition assessment, semi-automated assessment of breast adiposity (BA) from mammograms and fasting blood collection for biochemical analysis. Correlations and multivariate regression analysis were used to examine the associations of the BA with metabolic and body composition parameters. RESULTS: Of the 101 participants included in the final analysis, 76.2% were in menopause, and 23.8% were in premenopause. The BA was positively related with fasting plasma glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance, body mass index, waist circumference, body fat percentage, abdominal visceral and subcutaneous fat when adjusted for age among women in postmenopause. Also, the BA was an independent predictor of hyperglycemia and metabolic syndrome. These associations were not present among women in premenopause. CONCLUSION: The BA was related to different adverse body composition and metabolic factors in women in postmenopause. The results suggest that there might be a relevant BrAT endocrine role during menopause, whose mechanisms are yet to be clarified, which thus opens up research perspectives on the subject as well as on clinical settings.

Ameliorative effect of bofutsushosan (Fangfengtongshengsan) extract on the progression of aging-induced obesity.

This study aimed to compare fat accumulation in young and aged mice raised on a high-fat diet and to characterize the obesity-reducing effects of a Kampo medicine, bofutsushosan (BTS; fangfengtongshengsan in Chinese). Aged mice fed a high-fat diet containing 2% BTS extract for 28 days exhibited a significant reduction in weight gain and accumulation of visceral and subcutaneous fat, which were greater degree of reduction than those of the young mice. When the treatment period was extended to two months, the serum aspartate aminotransferase and alanine aminotransferase levels and the accumulation of fat droplets in the hepatocytes decreased. The mRNA expression of mitochondrial uncoupling protein 1 (UCP1) in the brown adipose tissue was significantly reduced in the aged mice compared to the young mice but increased by 2% in the BTS-treated aged mice. Additionally, the effect of BTS extract on oleic acid-albumin-induced triglyceride accumulation in hepatoblastoma-derived HepG2 cells was significantly inhibited in a concentration-dependent manner. Evaluation of the single crude drug extracts revealed that Forsythia Fruit, Schizonepeta Spike, and Rhubarb were the active components in BTS extract. These results suggest that BTS extract is effective against visceral, subcutaneous, and ectopic fats in the liver, which tend to accumulate with aging. Thus, BTS extract is useful in preventing and ameliorating the development of obesity and metabolic syndrome.

Genetic correlations between liver fat content, metabolic health, and adiposity distribution in the Fels Longitudinal Study.

BACKGROUND AND AIMS: Hepatic steatosis is known to be heritable, but its genetic basis is mostly uncharacterized. Steatosis is associated with metabolic and adiposity features; recent studies hypothesize that shared genetic effects between these traits could account for some of the unexplained heritability. This study aimed to quantify these genetic associations in a family-based sample of non-Hispanic white adults. METHODS AND RESULTS: 704 participants (18-95 years, 55.8% female) from the Fels Longitudinal Study with an MRI assessment of liver fat were included. Quantitative genetic analyses estimated the age- and sex-adjusted heritability of individual traits and the genetic correlations within trait pairs. Mean liver fat was 5.95% (SE = 0.23) and steatosis (liver fat >5.56%) was present in 29.8% of participants. Heritability (h2± SE) of steatosis was 0.72 ± 0.17 (p = 6.80e-6). All other traits including liver enzymes, fasting glucose, HOMA-IR, visceral and subcutaneous adipose tissue (VAT, SAT), body mass index, body fat percent, waist circumference, lipids and blood pressure were also heritable. Significant genetic correlations were found between liver fat and all traits except aspartate aminotransferase (AST), and among most trait pairs. Highest genetic correlations were between liver fat and HOMA-IR (0.85 ± 0.08, p = 1.73e-8), fasting glucose and ALT (0.89 ± 0.26, p = 6.68e-5), and HOMA-IR with: waist circumference (0.81 ± 0.12, p = 3.76e-6), body fat percent (0.78 ± 0.12 p = 2.42e-5) and VAT (0.73 ± 0.07, p = 6.37e-8). CONCLUSIONS: Common genes may exist between liver fat accumulation, metabolic features and adiposity phenotypes.

Linking sarcopenia, brain structure and cognitive performance: a large-scale UK Biobank study.

Sarcopenia refers to age-related loss of muscle mass and function and is related to impaired somatic and brain health, including cognitive decline and Alzheimer's disease. However, the relationships between sarcopenia, brain structure and cognition are poorly understood. Here, we investigate the associations between sarcopenic traits, brain structure and cognitive performance. We included 33 709 UK Biobank participants (54.2% female; age range 44-82 years) with structural and diffusion magnetic resonance imaging, thigh muscle fat infiltration (n = 30 561) from whole-body magnetic resonance imaging (muscle quality indicator) and general cognitive performance as indicated by the first principal component of a principal component analysis across multiple cognitive tests (n = 22 530). Of these, 1703 participants qualified for probable sarcopenia based on low handgrip strength, and we assigned the remaining 32 006 participants to the non-sarcopenia group. We used multiple linear regression to test how sarcopenic traits (probable sarcopenia versus non-sarcopenia and percentage of thigh muscle fat infiltration) relate to cognitive performance and brain structure (cortical thickness and area, white matter fractional anisotropy and deep and lower brain volumes). Next, we used structural equation modelling to test whether brain structure mediated the association between sarcopenic and cognitive traits. We adjusted all statistical analyses for confounders. We show that sarcopenic traits (probable sarcopenia versus non-sarcopenia and muscle fat infiltration) are significantly associated with lower cognitive performance and various brain magnetic resonance imaging measures. In probable sarcopenia, for the included brain regions, we observed widespread significant lower white matter fractional anisotropy (77.1% of tracts), predominantly lower regional brain volumes (61.3% of volumes) and thinner cortical thickness (37.9% of parcellations), with |r| effect sizes in (0.02, 0.06) and P-values in (0.0002, 4.2e-29). In contrast, we observed significant associations between higher muscle fat infiltration and widespread thinner cortical thickness (76.5% of parcellations), lower white matter fractional anisotropy (62.5% of tracts) and predominantly lower brain volumes (35.5% of volumes), with |r| effect sizes in (0.02, 0.07) and P-values in (0.0002, 1.9e-31). The regions showing the most significant effect sizes across the cortex, white matter and volumes were of the sensorimotor system. Structural equation modelling analysis revealed that sensorimotor brain regions mediate the link between sarcopenic and cognitive traits [probable sarcopenia: P-values in (0.0001, 1.0e-11); muscle fat infiltration: P-values in (7.7e-05, 1.7e-12)]. Our findings show significant associations between sarcopenic traits, brain structure and cognitive performance in a middle-aged and older adult population. Mediation analyses suggest that regional brain structure mediates the association between sarcopenic and cognitive traits, with potential implications for dementia development and prevention.

Vitamin D and the Metabolic Phenotype in Weight Loss After Bariatric Surgery: A Longitudinal Study.

PURPOSE: To evaluate the influence of vitamin D (VD) concentrations coupled with metabolic phenotypes preoperatively and 6 months after Roux-en-Y gastric bypass (RYGB) on body variables and weight loss. MATERIALS AND METHODS: A longitudinal, retrospective, analytical study comprising 30 adult individuals assessed preoperatively (T0) and 6 months (T1) after undergoing Roux-en-Y gastric bypass. The participants were distributed preoperatively into metabolically healthy obese (MHO) and metabolically unhealthy obese individuals (MUHO) according to the HOMA-IR classification, as well as the adequacy and inadequacy of vitamin D concentrations in the form of 25(OH)D. All participants were assessed for weight, height, body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), visceral adiposity index (VAI), body circularity index (BCI), body adiposity index (BAI), weight loss, and assessment of 25(OH)D and 1,25(OH)2D concentrations using high-performance liquid chromatography with an ultraviolet detector (HPLC-UV). The statistical program used was SPSS version 21. RESULTS: VD adequacy and a healthy phenotype in the preoperative period may play an important role concerning body fat distribution, as the body averages for WHtR (0.020*) and BCI (0.020*) were lower in MHO participants. In comparison, those with VD inadequacy and MUHOs had higher BAI averages (0.000*) in the postoperative period. Furthermore, it is possible that VD inadequacy before and after RYGB, even in the presence of an unhealthy phenotype, may contribute to the increase in VAI values (0.029*) after this surgery. Only those with inadequate VD and MUHOs had higher 25(OH)D concentrations. Besides, this unhealthy phenotype had a greater reduction in BMI in the early postoperative period (p < 0.001). CONCLUSION: This study suggests that VD adequacy and the presence of a healthy phenotype appear to have a positive impact on the reduction of visceral fat in the context of pre- and postoperative obesity. In addition, there was a greater weight reduction in those with VD inadequacy and in MUHO, which suggests that the volumetric dilution effect of VD and catabolism after bariatric surgery is more pronounced in this specific metabolic phenotype.

Association between type 2 diabetes mellitus and body composition based on MRI fat fraction mapping.

Purpose: To explore the association between type 2 diabetes mellitus (T2DM) and body composition based on magnetic resonance fat fraction (FF) mapping. Methods: A total of 341 subjects, who underwent abdominal MRI examination with FF mapping were enrolled in this study, including 68 T2DM patients and 273 non-T2DM patients. The FFs and areas of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and abdominal muscle (AM) were measured at the level of the L1-L2 vertebral. The FF of bone marrow adipose tissue (BMAT) was determined by the averaged FF values measured at the level of T12 and L1 vertebral, respectively. The whole hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) were measured based on 3D semi-automatic segmentation on the FF mapping. All data were analyzed by GraphPad Prism and MedCalc. Results: VAT area, VAT FF, HFF, PFF of T2DM group were higher than those of non-T2DM group after adjusting for age and sex (P < 0.05). However, there was no differences in SAT area, SAT FF, BMAT FF, AM area and AM FF between the two groups (P > 0.05). VAT area and PFF were independent risk factors of T2DM (all P < 0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) for VAT area and PFF in differentiating between T2DM and non-T2DM were 0.685 and 0.787, respectively, and the AUC of PFF was higher than VAT area (P < 0.05). Additionally, in seemingly healthy individuals, the SAT area, VAT area, and AM area were found to be significantly associated with being overweight and/or obese (BMI ≥ 25) (all P < 0.05). Conclusions: In this study, it was found that there were significant associations between T2DM and VAT area, VAT FF, HFF and PFF. In addition, VAT area and PFF were the independent risk factors of T2DM. Especially, PFF showed a high diagnostic performance in discrimination between T2DM and non-T2DM. These findings may highlight the crucial role of PFF in the pathophysiology of T2DM, and it might be served as a potential imaging biomarker of the prevention and treatment of T2DM. Additionally, in individuals without diabetes, focusing on SAT area, VAT area and AM area may help identify potential health risks and provide a basis for targeted weight management and prevention measures.

Behind BMI: The Potential Indicative Role of Abdominal Ectopic Fat on Glucose Metabolism.

INTRODUCTION: The purpose of this study was to compare the difference in abdominal fat distribution between different metabolic groups and find the ectopic fat with the most risk significance. METHODS: A total of 98 subjects were enrolled; there were 53 cases in the normal glucose metabolism group and 45 cases in the abnormal glucose metabolism group. Chemical shift-encoded magnetic resonance imaging was applied for quantification of pancreatic fat fraction (PFF) and hepatic fat fraction (HFF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT). The correlation and the difference of fat distribution between different metabolism groups were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the suggestive effect of different body fat fraction. RESULTS: Correlation analysis showed that body mass index (BMI) had the strongest correlation with fasting insulin (r = 0.473, p < 0.001), HOMA-IR (r = 0.363, p < 0.001), and C-reactive protein (r = 0.245, p < 0.05). Pancreatic fat has a good correlation with fasting blood glucose (r = 0.247, p < 0.05) and HbA1c (r = 0.363, p < 0.001). With the increase of BMI, PFF, VAT, and SAT showed a clear upward trend, but liver fat was distributed relatively more randomly. The pancreatic fat content in the abnormal glucose metabolism group is significantly higher than that in the normal group, and pancreatic fat is also a reliable indicator of abnormal glucose metabolism, especially in the normal and overweight groups (the area under the curve was 0.859 and 0.864, respectively). CONCLUSION: MR-based fat quantification techniques can provide additional information on fat distribution. There are differences in fat distribution among people with different metabolic status. People with more severe pancreatic fat deposition have a higher risk of glucose metabolism disorders.

Independent association of thigh muscle fat density with vascular events in Korean adults.

BACKGROUND: We aimed to explore the associations between thigh muscle fat density and vascular events. METHODS: A total of 3,595 adults (mean age, 57.2 years; women, 1,715 [47.7%]) without baseline cardiovascular events from the Korean Atherosclerosis Study-2 were included. Muscle and fat area at the mid-thigh level were measured by computed tomography (CT) using the following Hounsfield Unit range: 0-30 for low density muscle (LDM); 31-100 for normal density muscle (NDM); and - 250 to - 50 for fat. RESULTS: During a median follow-up period of 11.8 (4.3-13.9) years, vascular events occurred in 11.6% of men and 5.9% of women. Individuals with vascular events had a larger LDM area (men: 48.8 ± 15.5 cm2 vs. 44.6 ± 14.5 cm2; women: 39.4 ± 13.2 cm2 vs. 35.0 ± 11.8 cm2, both P < 0.001) compared with those who did not have vascular events during the follow-up of at least 5 years. The LDM/NDM ratio was also independently associated with vascular events after adjusting for cardiometabolic risk factors. Moreover, the LDM/NDM ratio improved the prognostic value for vascular events when added to conventional risk factors. CONCLUSIONS: The current study suggests that a higher thigh muscle fat infiltration is associated with an increased risk of developing vascular events among Korean adults.

Effects of liraglutide on intrapancreatic fat deposition in patients with type 2 diabetes.

BACKGROUND & AIMS: Ectopic fat deposition is associated with worsening of glycemic control. This study was conducted to determine whether liraglutide reduces ectopic fat deposition, especially in pancreas, in patients with type 2 diabetes (T2D). METHODS: We retrospectively recruited T2D patients who underwent abdominal unenhanced CT scans both before and after administration of liraglutide (N = 13) or glimepiride (N = 29). Using CT values of pancreas (P), liver (L) and spleen (S), we defined the indices of intrapancreatic and liver fat as P-S value and L-S value, respectively. Increase of each value suggests the reduction of each fat deposition. RESULTS: The values of HbA1c (p = 0.0017) and body weight (p = 0.0081) decreased, and L-S (p = 0.0024) increased significantly after administration of liraglutide compared with those at baseline. Similarly, P-S tended to increase in the liraglutide group (p = 0.0547) and increased significantly in the liraglutide subgroup with fatty pancreas (p = 0.0303), defined as having baseline P-S less than -5. In the glimepiride group, P-S did not increase regardless of baseline P-S. Among patients with fatty pancreas, administration of liraglutide tended to be a significant factor for the change in P-S after adjustment for the change in HbA1c (p = 0.1090) and the change in visceral fat area (p = 0.1030). CONCLUSIONS: Intrapancreatic fat deposition was decreased after treatment with liraglutide, but not glimepiride, in T2D patients with fatty pancreas. Liraglutide might reduce intrapancreatic fat deposition independently of decreases in HbA1c and visceral fat volume.

Adolescent polycystic ovary syndrome without obesity: HOTAIR rs1443512 genotype relates to fat mass and to the redistribution of fat mass on low-dose pioglitazone.

INTRODUCTION: Adolescent polycystic ovary syndrome (PCOS) is characterized by androgen excess and oligo-amenorrhea, and often results from ectopic lipid storage due to a mismatch between early adipogenesis and later lipogenesis. Endogenous HOX transcript antisense RNA (HOTAIR) and exogenous pioglitazone are enhancers of subcutaneous adipogenesis, particularly in the gluteofemoral region. The A allele of HOTAIR rs1443512 is an equivalent of a natural knock-down and is, thus, a candidate to influence the distribution of fat mass, and also the redistribution of fat mass by pioglitazone in adolescent PCOS-without-obesity. SUBJECTS AND METHODS: We performed two post hoc analyses by HOTAIR rs1443512 genotype. In the first, we analyzed the pooled pre-treatment data (auxology; endocrinology; body composition by dual X-ray absorptiometry; abdominal fat distribution by magnetic resonance imaging) of 65 adolescent girls with PCOS-without-obesity in three reported studies (ISRCTN45546616; ISRCTN29234515; ISRCTN11062950). In the second, we analyzed the results of 24 adolescent girls with PCOS-without-obesity, who received pioglitazone (7.5 mg/d for 1 year) as part of a randomized combination treatment (with spironolactone and metformin) in two reported studies (ISRCTN29234515; ISRCTN11062950). All data had been obtained in a blinded-to-genotype way. RESULTS: The pre-treatment data disclosed that the girls-with-A-allele of HOTAIR rs1443512 had developed PCOS with a lower BMI (22.3 ± 2.3 kg/m2; N = 17) than the other girls (24.1 ± 2.7 kg/m2; N = 48), this difference being essentially attributable to a lower fat mass (mean difference 4.6 kg; P < 0.01). On low-dose pioglitazone, girls-with-A-allele (N = 12) raised their fat mass while the other girls (N = 12) did not (total fat mass + 2.2 ± 1.8 kg vs - 0.9 ± 2.2 kg; P < 0.001), particularly in the gynoid area (gluteofemoral fat + 0.6 ± 0.4 kg vs - 0.1 ± 0.5 kg; hip circumference + 2.3 ± 1.9 cm vs - 1.7 ± 3.1 cm; both P < 0.001). CONCLUSION: The present findings suggest that the HOTAIR rs1443512 genotype influences not only the distribution of fat mass in adolescent girls with PCOS-without-obesity but also the redistribution of fat mass during prolonged treatment with low-dose pioglitazone. TRIAL REGISTRATION: ISRCTN45546616 ( https://doi.org/10.1186/ISRCTN45546616 ). ISRCTN29234515 ( https://doi.org/10.1186/ISRCTN29234515 ). ISRCTN11062950 ( https://doi.org/10.1186/ISRCTN11062950 ).

Associations of infant feeding practices with abdominal and hepatic fat measures in childhood in the longitudinal Healthy Start Study.

BACKGROUND: Infant feeding patterns have been linked with obesity risk in childhood, but associations with precise measures of body fat distribution are unclear. OBJECTIVE: We examined associations of infant feeding practices with abdominal fat and hepatic fat trajectories in childhood. METHODS: This study included 356 children in the Healthy Start Study, a prospective prebirth cohort in Colorado. Infant feeding practices were assessed by postnatal interviews and categorized as any human milk <6 mo compared with ≥6 mo; complementary foods introduced ≤4 mo compared with >4 mo; soda introduced ≤18 mo compared with >18 mo. Abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) areas and hepatic fat (%) were assessed by magnetic resonance imaging in early and middle childhood (median 5 and 9 y old, respectively). We examined associations of infant feeding with adiposity trajectories across childhood using linear mixed models. RESULTS: In the sample of children, 67% consumed human milk ≥6 mo, 75% were introduced to complementary foods at >4 mo, and 81% were introduced to soda at >18 mo. We did not find any associations between duration of any human milk consumption and childhood adiposity trajectories. Early introduction to complementary foods (≤4 mo) was associated with faster rates of change for SAT and VAT during childhood (Slope [95% CI]: 15.1 [10.7,19.4] cm2/y for SAT; 2.5 [1.9,2.9] cm2/y for VAT), compared with introduction at >4 mo (5.5 [3.0,8.0] cm2/y and 1.6 [1.3,1.9] cm2/y, respectively). Similarly, early introduction to soda (≤18 mo) was associated with faster rates of change for all 3 outcomes during childhood (Slope [95% CI]: 20.6 [15.0,26.1] cm2/y for SAT, 2.7 [2.0,3.3] cm2/y for VAT, 0.3 [0.1,0.5] %/year for hepatic fat) compared with delayed introduction (5.4 [2.8,8.0] cm2/y, 1.7 [1.3, 2.0] cm2/y, -0.1 [-0.2,0.0] %/y, respectively). CONCLUSIONS: The timing of introduction and quality of complementary foods in infancy was associated with rates of abdominal and hepatic fat accrual during childhood. Experimental studies are needed to assess underlying mechanisms.

Muscle Quality and Risk of Metabolic Syndrome in Adult Patients with Inherited Metabolic Diseases.

Adult patients with several Inherited Metabolic Diseases (IMD) follow diets controlled in proteins, rich in carbohydrates, and free amino acids formulae, which cause hyperinsulinism and ectopic fat. Previous studies showed IMD adult patients have a higher prevalence of metabolic syndrome and their complications [1]. Recently, ultrasound [US) has been validated for malnutrition, assessing muscle quality subjectively [2]. Higher echo intensity (EI) is associated with poorer muscle quality and functional results in aging [3] and other clinical settings, but it has never been evaluated in IMD. US measurements were conducted on 19 IMD patients and 6 healthy controls at Hospital Universitario de Badajoz (HUB) to assess EI, anthropometry, bioimpedance, and biochemistry. The HUB ethics committee approved the protocol and informed consent. Statistics were made with Jamovi. The mean age was 29.9 (range 18-47) in IMD patients vs. 33.7 (26-47) in controls. The distribution of IMD is shown in Figure 2. The mean EI in IMD was 56.9 (60.9 in PKU) vs. 54.4 in controls, NOT being the differences statistically significant (t- Student p =0.633; in PKU, p =0.246). The box plot is shown in Figure 3. IMD patients had excess body fat in a variable degree depending on the method (Figure 4): anthropometry, BIA, preperitoneal fat or myosteatosis. 40% had insulin resistance by HOMA, 20% prediabetes by HbA1c, 58.8% had low HDL-cholesterol levels, and 29.4% had hypertriglyceridemia. Insulin resistance status is shown in Figure 5. Obesity by anthropometry was significantly correlated with subcutaneous abdominal and preperitoneal fat by ultrasound and fat mass by BIA. Fat mass by BIA was correlated to preperitoneal fat, and fat-free mass by BIA with HOMA and degree of metabolic control of IMD. Muscle quality, by an objective tool, such as echo intensity, is worse in patients with IMD than in controls, reflecting poorer muscle metabolic condition and a higher risk of metabolic syndrome. It is not statistically significant, probably due to the small sample size. The prevalence of obesity and other metabolic syndrome components is higher in IMD patients than in the general population of the same age. Body composition analysis by BIA and nutritional ultrasound can help to identify patients at risk of metabolic syndrome before biochemical markers show.

Intrapancreatic fat deposition and nutritional treatment: the role of various dietary approaches.

Ectopic fat accumulation in various organs and tissues, such as the liver, muscle, kidney, heart, and pancreas, is related to impaired capacity of adipose tissue to accumulate triglycerides, as a consequence of overnutrition and an unhealthy lifestyle. Ectopic fat promotes organ dysfunction and is a key factor in the development and progression of cardiometabolic diseases. Interest in intrapancreatic fat deposition (IPFD) has developed in the last few years, particularly in relation to improvement in methodological techniques for detection of fat in the pancreas, and to growing evidence for the role that IPFD might have in glucose metabolism disorders and cardiometabolic disease. Body weight reduction represents the main option for reducing fat, and the evidence consistently shows that hypocaloric diets are effective in reducing IPFD. Changes in diet composition, independently of changes in energy intake, might offer a more feasible and safe alternative treatment to energy restriction. This current narrative review focused particularly on the possible beneficial role of the diet and its nutrient content, in hypocaloric and isocaloric conditions, in reducing IPFD in individuals with high cardiometabolic risk, highlighting the possible effects of differences in calorie quantity and calorie quality. This review also describes plausible mechanisms by which the various dietary approaches could modulate IPFD.

Ectopic and visceral fat deposition in aging, obesity, and idiopathic pulmonary fibrosis: an interconnected role.

Idiopathic pulmonary fibrosis (IPF) is considered an age-related disease. Age-related changes, along with other factors such as obesity, hormonal imbalances, and various metabolic disorders, lead to ectopic fat deposition (EFD). This accumulation of fat outside of its normal storage sites is associated with detrimental effects such as lipotoxicity, oxidative stress, inflammation, and insulin resistance. This narrative review provides an overview of the connection between ectopic and visceral fat deposition in aging, obesity, and IPF. It also elucidates the mechanism by which ectopic fat deposition in the airways and lungs, pericardium, skeletal muscles, and pancreas contributes to lung injury and fibrosis in patients with IPF, directly or indirectly. Moreover, the review discusses the impact of EFD on the severity of the disease, quality of life, presence of comorbidities, and overall prognosis in IPF patients. The review provides detailed information on recent research regarding representative lipid-lowering drugs, hypoglycemic drugs, and lipid-targeting drugs in animal experiments and clinical studies. This may offer new therapeutic directions for patients with IPF.

Identifying obesity subtypes: A review of studies utilising clinical biomarkers and genetic data.

Obesity is a complex and multifactorial condition that poses significant health risks. Recent advancements in our understanding of obesity have highlighted the heterogeneity within this disorder. Identifying distinct subtypes of obesity is crucial for personalised treatment and intervention strategies. This review paper aims to examine studies that have utilised clinical biomarkers and genetic data to identify clusters or subtypes of obesity. The findings of these studies may provide valuable insights into the underlying mechanisms and potential targeted approaches for managing obesity-related health issues such as type 2 diabetes.