The Effects of Exercise Interventions on Ectopic and Subcutaneous Fat in Patients with Type 2 Diabetes Mellitus: A Systematic Review, Meta-Analysis, and Meta-Regression.

Background/Objectives: The aim of the present study was to determine the effects of exercise training on ectopic and subcutaneous fat in patients with type 2 diabetes mellitus (T2DM). Methods: Web of Science, PubMed, and Scopus were searched for original articles published through November 2023 that included exercise versus control interventions on body mass (BM), liver fat percentage, visceral fat area (VFA), subcutaneous fat area (SFA), and intramuscular fat volume or mass (IMF) in patients with T2DM. Weighted mean differences (WMDs) for liver fat and BM, standardized mean differences (SMDs) for VFA, SFA, and IMF, and 95% confidence intervals (95% CIs) were determined using random-effects models. Results: Thirty-six studies comprising 2110 patients with T2DM were included in the present meta-analysis. Exercise training effectively reduced BM [WMD = -2.502 kg, p = 0.001], liver fat% [WMD = -1.559%, p = 0.030], VFA [SMD = -0.510, p = 0.001], and SFA [SMD = -0.413, p = 0.001] in comparison to the control. The IMF [SMD = 0.222, p = 0.118] remained unchanged compared to the controls. Subgroup analyses showed that the type of exercise, duration, and body mass index (BMI) of participants were sources of heterogeneity. Conclusions: The current meta-analysis provides strong evidence that exercise training, particularly aerobic and combined (aerobic and resistance) exercise programs, is effective for reducing BM, VFA, and SFA in patients with T2DM. However, aerobic exercise was more effective for reducing liver fat than combined exercise. The beneficial effects of exercise on VFA and SFA reduction, but not liver fat, are associated with weight loss. These findings highlight the importance of including consistent exercise as a key management component for T2DM and associated ectopic fat deposition, with potential long-term benefits for metabolic health.

Rationale and Design of the Study to Investigate the Metabolic Action of Imeglimin on Patients with Type 2 Diabetes Mellitus (SISIMAI).

INTRODUCTION: Imeglimin is a first-in-class, novel, oral glucose-lowering agent for the treatment of type 2 diabetes mellitus. The efficacy and safety of imeglimin as an antidiabetic agent have been investigated in clinical trials. However, its metabolic effects in humans have not yet been fully elucidated. METHODS: The Study to InveStIgate the Metabolic Action of Imeglimin on patients with type 2 diabetes mellitus (SISIMAI) is a single-arm intervention study. In this study, we have recruited 25 patients with type 2 diabetes to receive 2000 mg/day imeglimin for 20 weeks. We perform a 75-g oral glucose tolerance test (OGTT) with double-glucose tracers, a two-step hyperinsulinemic-euglycemic clamp with glucose tracer, ectopic fat measurement by proton magnetic resonance spectroscopy, visceral/subcutaneous fat area measurement by magnetic resonance imaging, muscle biopsy, and evaluation of fitness level by cycle ergometer before and after imeglimin administration. PLANNED OUTCOMES: The primary outcome is the change in area under the curve of glucose levels during the OGTT after 20 weeks of imeglimin treatment. We also calculate the endogenous glucose production, rate of oral glucose appearance, and rate of glucose disappearance from the data during the 75-g OGTT and compare them between pre- and post-treatment. Additionally, we will compare other parameters, such as the changes in tissue-specific insulin sensitivity, ectopic fat accumulation, visceral/subcutaneous fat area accumulation, and fitness level between each point. This is the first study to investigate the organ-specific metabolic action of imeglimin in patients with type 2 diabetes mellitus using the 75-g OGTT with the double tracer method. The results of this study are expected to provide useful information for drug selection based on the pathophysiology of individual patients with type 2 diabetes mellitus. TRIAL REGISTRATION: jRCTs031210600.

Effects of Obesity and Exercise on Hepatic and Pancreatic Lipid Content and Glucose Metabolism: PET Studies in Twins Discordant for BMI.

Obesity and sedentarism are associated with increased liver and pancreatic fat content (LFC and PFC, respectively) as well as impaired organ metabolism. Exercise training is known to decrease organ ectopic fat but its effects on organ metabolism are unclear. Genetic background affects susceptibility to obesity and the response to training. We studied the effects of regular exercise training on LFC, PFC, and metabolism in monozygotic twin pairs discordant for BMI. We recruited 12 BMI-discordant monozygotic twin pairs (age 40.4, SD 4.5 years; BMI 32.9, SD 7.6, 8 female pairs). Ten pairs completed six months of training intervention. We measured hepatic insulin-stimulated glucose uptake using [18F]FDG-PET and fat content using magnetic resonance spectroscopy before and after the intervention. At baseline LFC, PFC, gamma-glutamyl transferase (GT), and hepatic glucose uptake were significantly higher in the heavier twins compared to the leaner co-twins (p = 0.018, p = 0.02 and p = 0.01, respectively). Response to training in liver glucose uptake and GT differed between the twins (Time*group p = 0.04 and p = 0.004, respectively). Liver glucose uptake tended to decrease, and GT decreased only in the heavier twins (p = 0.032). In BMI-discordant twins, heavier twins showed higher LFC and PFC, which may underlie the observed increase in liver glucose uptake and GT. These alterations were mitigated by exercise. The small number of participants makes the results preliminary, and future research with a larger pool of participants is warranted.

Comprehensive assessment of distinct abdominal fat compartments beyond liver content in overweight/obese patients using MRI and ultrasound imaging.

BACKGROUND: Ectopic fat deposition, involving lipid infiltration within organs and fat accumulating surrounding organs, plays a crucial role in the development of metabolic abnormalities in obesity. Current imaging measurements of obesity primarily focus on lipid infiltration within liver, neglecting fat deposition in other areas. This study aims to explore the methods of measuring and correlating different types of abdominal ectopic fat deposition in obese patients using magnetic resonance imaging (MRI) and ultrasound techniques, and to investigate the relationship between these fat parameters and obesity-related metabolic markers. METHODS: Abdominal ectopic fat deposition including liver fat content, mesenteric fat thickness (MFT), perirenal fat thickness (PrFT) and preperitoneal fat thickness (PFT) were measured in 220 overweight/obese patients using both MRI and ultrasound techniques. Correlation analysis validated the concordance of fat parameters at specific sites between the two imaging methods and identified the cutoff values of hepatic attenuation coefficient (AC) for diagnosis of liver steatosis. Additionally, we investigated the correlation between fat parameters by both methods and obesity-related metabolic markers. RESULTS: Ultrasonic measurement of PrFT and hepatic AC both had high correlation with PrFT (r = 0.829, p < 0.001) and hepatic Proton-density fat fraction (PDFF, r = 0.822, p < 0.001) measured via MR. Hepatic AC cutoff values for diagnosing mild, moderate, and severe fatty liver were 0.705 dB/cm/MHz (AUC = 0.922), 0.755 dB/cm/MHz (AUC = 0.923), and 0.875 dB/cm/MHz (AUC = 0.890) respectively. Hepatic AC correlated significantly with AST and ALT (r = 0.477 ~ 0.533, p < 0.001). MFT measured by ultrasound were positively associated with glycated hemoglobin (r = 0.324 ~ 0.371, p < 0.001) and serum triglyceride levels (r = 0.303 ~ 0.353, p < 0.001). PrFT measured by both methods showed significant positive correlations with serum creatinine levels (r = 0.305 ~ 0.308, p < 0.001). CONCLUSIONS: Both MRI and ultrasound demonstrate metabolic correlations in quantifying mesenteric, hepatic, and perirenal fat. In addition to assessment of liver fat content, the measurements of ectopic fat deposition by MRI or ultrasound are a simple and crucial way for comprehensive fat evaluation in individuals with overweight/obesity.

Ethnic differences in the relationship between ectopic fat deposition and insulin sensitivity in Black African and White European men across a spectrum of glucose tolerance.

AIM: To examine the hypothesis that there would be ethnic differences in the relationship between ectopic fat and tissue-specific insulin resistance (IR) across a spectrum of glucose tolerance in Black African (BA) and White European (WE) men. MATERIALS AND METHODS: Fifty-three WE men (23/10/20 normal glucose tolerance [NGT]/impaired glucose tolerance [IGT]/type 2 diabetes [T2D]) and 48 BA men (20/10/18, respectively) underwent a two-step hyperinsulinaemic-euglycaemic clamp with infusion of D-[6,6-2H2]-glucose and [2H5]-glycerol to assess hepatic, peripheral and adipose tissue IR. Magnetic resonance imaging was used to measure subcutaneous adipose tissue, visceral adipose tissue (VAT) and intrahepatic lipid (IHL). Associations between ectopic fat and IR were assessed using linear regression models. RESULTS: There were no differences in tissue-specific IR between ethnic groups at any stage of glucose tolerance. VAT level was consistently lower in the BA population; NGT (p = 0.013), IGT (p = 0.006) and T2D (p = 0.015). IHL was also lower in the BA compared with the WE men (p = 0.013). VAT and IHL levels were significantly associated with hepatic IR in the BA population (p = 0.001) and with peripheral IR in the WE population (p = 0.027). CONCLUSIONS: The present study suggests that BA and WE men exhibit the same degree of IR across a glucose tolerance continuum, but with lower VAT and IHL levels in the BA population, suggesting that IR may be driven by a mechanism other than increased ectopic fat accumulation in BA men.

Assessment of aortic perivascular and renal sinus fat in endogenous cortisol excess of different etiology.

OBJECTIVE: Endogenous cortisol excess is known to affect body fat distribution. Ectopic fat is the accumulation of triglycerides in non-adipose tissue regions that normally contain little fat. The aim of study was to investigate the amount of ectopic fat in aortic perivascular and renal sinus fat of patients with endogenous cortisol excess and its relationship with their comorbitidies and laboratory findings. DESIGN: A total of 119 patients, including 16 patients with pituitary Cushing's disease (CD), 21 patients with adrenal Cushing's syndrome (CS), 34 patients with mild autonomous cortisol secretion (MACS), and 48 patients with nonfunctioning adrenal adenomas were enrolled in this retrospective study. Aortic perivascular fat and renal sinus fat were evaluated with magnetic resonance imaging. RESULTS: It was determined that the amount of aortic perivascular fat was increased in patients with CD (P = 0.01). The linear regression analysis showed that the amount of perivascular fat was associated with triglyceride levels and cortisol levels after the 1 mg dexamethasone suppression test as well as with gender (P < 0.01). Renal sinus fat measurements were similar in the groups (P > 0.05). After adjusting for age, sex, and BMI, perivascular fat was found to be higher in pituitary the CD than in the MACS and the nonfunctioning adenoma groups, and renal sinus fat was seen to be higher in pituitary the CD than in the MACS groups (P < 0.05). Patients with diabetes mellitus had an increased amount of renal sinus fat (P = 0.008). CONCLUSION: The amount of perivascular and renal sinus fat may increase in patients with CD. Further studies are needed to elucidate ectopic fat distribution in patients with endogenous cortisol excess.

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 with 86 healthy males in 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 (-3.3%, P < 0.05) fat compared with 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, whereas subcutaneous (-2.7 ± 5.1 mL, NS), liver (-0.5 ± 0.9%, NS), and cardiac (-0.3 ± 2.3 mL, NS) fat 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.NEW & NOTEWORTHY Even when being accompanied by a substantial increase in energy intake to compensate energy expenditure and limit weight loss, a large volume of endurance exercise performed within a short period of time is associated with a significant reduction in visceral adiposity. High cardiorespiratory fitness is associated with low levels of liver fat in middle-aged males.

[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.

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.

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.

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 (MetS). Despite significant changes in body composition over women's lifespans, 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 and performed 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 associations of 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, and abdominal visceral and subcutaneous fat when adjusted for age among women in postmenopause. Also, the BA was an independent predictor of hyperglycemia and MetS. 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, with mechanisms yet to be clarified, thus opening up research perspectives on the subject and potential clinical implications.

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.

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.

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.

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.

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.

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.

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.