Liver fibrosis, NT-ProBNP and mortality in patients with MASLD: A population-based cohort study.

BACKGROUND & AIM: Liver fibrosis is the strongest predictor of liver-related mortality in many chronic liver diseases. NT-ProBNP is independently associated with cardiovascular mortality in general population settings. Here, we evaluate the relative contribution of non-invasively identified liver fibrosis and NT-ProBNP on all-cause and cardiovascular mortality in patients with metabolic (dysfunction)-associated steatotic liver disease (MASLD). METHODS AND RESULTS: Serum NT-ProBNP levels were measured in 4229 patients with MASLD from the general population without a known history of heart failure that participated in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. Presence of liver fibrosis was estimated using the Fibrosis-4 index (FIB-4). We applied Cox proportional hazard models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP and FIB-4 levels and all-cause and cardiovascular mortality through December 2019. Mortality was lower for participants with normal levels of both biomarkers, intermediate if a single biomarker was elevated and highest when both were above the chosen threshold. In the multivariable-adjusted models, both elevated FIB-4 (≥2.67) and elevated NT-ProBNP levels (≥125 pg/ml) were independently associated with higher risks of all-cause mortality (HR 2.2, 95 % CI 1.5-3.2 and HR 1.6, 95 % CI 1.4-2.0, respectively) and cardiovascular mortality (HR 2.1, 95 % CI 1.2-3.7 and HR 2.1, 95 % CI 1.5-2.9, respectively). The associations remained consistent in subgroup analyses based on sex, obesity and age. CONCLUSIONS: Both FIB-4 and NT-ProBNP are independently associated with higher mortality in patients with MASLD. Their combined use might prove useful to risk-stratify patients in clinical practice.

Differential Association of Sex Hormones with Metabolic Parameters and Body Composition in Men and Women from the United States.

Sex hormones impact body composition. Data on the specific impact of each hormone on different body depots in men and women are scarce. The aim of this study is to evaluate the association between testosterone, estradiol and body fat distribution in the general population. This is a population-based cross-sectional study based on data from the 2013-2016 cycles of the National Health and Nutrition Examination Survey. Dual energy X-ray absorptiometry (DXA) and liquid chromatography tandem mass spectrometry were performed on participants aged 18-59 years to evaluate body composition and sex hormone levels, respectively. Weighted multivariable linear regression analyses were performed to evaluate the association between these parameters after adjustment for potential confounders. A total of 6655 participants (3309 males and 3346 females) was included in the analysis. Men with lower testosterone levels were older, had a higher body mass index (BMI) and had a generally unfavorable metabolic profile, while no specific trends were found in women. Among men, testosterone was positively associated with lean body mass and was negatively associated with fat mass and the android/gynoid (A/G) ratio, while an opposite trend was found for estradiol. Among women, testosterone did not impact body composition, while estradiol levels were positively associated with lean mass and were negatively associated with fat mass. Our results support the notion that the impact of different sex hormones on specific fat depots varies substantially between men and women.

Serum neurofilament light chain levels are associated with all-cause mortality in the general US population.

INTRODUCTION: Serum neurofilament light chain (sNfL) levels are biomarkers of neuro-axonal injury in multiple neurological diseases. Little is known on their potential role as prognostic markers in people without known neurological conditions. OBJECTIVE: The aim of this study is to evaluate the association between sNfL levels and all-cause mortality in a general population setting. METHODS: sNfL levels were measured in 2071 people aged 25-75 years from the general US population that participated in the 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES). Cognitive function was evaluated in a subset of participants aged 60-75 years using the Consortium to Establish a Registry for Alzheimer's Disease-Word Learning test, the Animal Fluency test and the Digit Symbol Substitution test. We applied Cox proportional hazard models adjusted for several potential confounders to evaluate the association between sNfL and all-cause mortality through December 2019 by linking NHANES data with data from the National Death Index. RESULTS: In a cross-sectional analysis, higher sNfL levels were associated with worse performance in all three cognitive function tests. Over a median follow-up of 6.1 years, 85 participants died. In a multivariable model adjusted for age, sex, race-ethnicity, diabetes, chronic kidney disease, harmful alcohol consumption, cigarette smoke and prevalent cardiovascular disease, higher sNfL levels were significantly and positively associated with all-cause mortality (HR per unit increase in log-transformed sNfL: 2.46, 95% CI 1.77-3.43, p < 0.001). Results were robust when analyses were stratified according to age, sex, body mass index and kidney function. CONCLUSION: We found a positive association between sNfL levels and mortality in the general US population. Further studies are needed to understand the biological mechanisms underlying this association.

Low 25 (OH) vitamin D levels are associated with increased prevalence of nonalcoholic fatty liver disease and significant liver fibrosis.

AIMS: Evidence on the role of 25-Hydroxyvitamin D (25(OH)D) in the occurrence and progression of nonalcoholic fatty liver disease (NAFLD) is conflicting and population-based data are scarce. Here, we assess the association between 25(OH)D levels, NAFLD and liver fibrosis in the general population. MATERIALS AND METHODS: This is an analysis of data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey. We included adult participants with available data on vibration-controlled transient elastography (VCTE) and without viral hepatitis and significant alcohol consumption. Steatosis and fibrosis were diagnosed by the median values of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. 25(OH)D was measured by high performance liquid chromatography-tandem mass spectrometry. RESULTS: A total of 3970 participants (1928 men and 2042 women) were included in the study. The prevalence of NAFLD (CAP ≥ 274 dB/m) and significant liver fibrosis (LSM ≥ 8 kPa) were 41.7% (95% CI 39.4-44.0) and 8.4% (95% CI 7.0-9.9), respectively, while 21.1% (95% CI 17.3-25.4) of participants had low 25(OH)D levels (<50 nmol/L). A multivariable logistic regression model adjusted for age, sex, race-ethnicity, body mass index, waist circumference, calendar period, diabetes, chronic kidney disease, and vitamin D supplementation showed that compared with participants with low 25(OH)D, those with optimal levels (≥75 nmol/L) had lower odds of both NAFLD (OR 0.73, 95% CI 0.55-0.98 p = 0.038) and significant liver fibrosis (OR 0.65, 95% CI 0.44-0.96, p = 0.033). CONCLUSIONS: An inverse relationship was found between 25(OH)D and NAFLD and fibrosis, suggesting a possible role of vitamin D in NAFLD occurrence and progression.

Diabetes Mellitus is Associated With Higher Serum Neurofilament Light Chain Levels in the General US Population.

CONTEXT: Serum neurofilament light chain (sNfL) levels are biomarkers of neuroaxonal injury in multiple neurological diseases. OBJECTIVE: Given the paucity of data on the distribution of sNfL levels in the general population, in the present study we identified predictors of sNfL levels in a community setting and investigated the association between diabetes and sNfL. METHODS: sNfL levels were measured in 2070 people aged 20 to 75 years from the general US population (275 with and 1795 without diabetes) that participated in the 2013-2014 cycle of the National Health and Nutrition Examination Survey. We evaluated the association between diabetes and sNfL levels after adjustment for age, sex, race-ethnicity, alcohol use, and kidney function using a multivariable linear regression model. Cognitive function was evaluated in a subset of participants aged 60 to 75 years using the Consortium to Establish a Registry for Alzheimer's Disease-Word Learning test, the Animal Fluency test, and the Digit Symbol Substitution test. RESULTS: The weighted prevalence of diabetes was 10.4% (95% CI, 9.0-11.9). In each age stratum, patients with diabetes exhibited higher sNfL levels compared with nondiabetic participants. Age, proportion of males, prevalence of diabetes, and homeostatic model of insulin resistance increased progressively across quartiles of sNfL levels in the overall population, whereas estimated glomerular filtration rate (eGFR) showed an opposite trend. In the multivariable model, age, sex, eGFR, alcohol use and diabetes were significantly associated with sNfL levels. Moreover, higher sNfL levels were associated with worse performance in all 3 cognitive function tests. CONCLUSION: Diabetes is associated with higher sNfL. Further large-scale and prospective studies are needed to replicate our results and evaluate the ability of sNfL to predict the incidence of neuropathy and dementia in this patient population.

NT-ProBNP and mortality across the spectrum of glucose tolerance in the general US population.

BACKGROUND: Even though hyperglycemia is a well-known cardiovascular risk factor, the absolute risk of cardiovascular events varies to a great extent within each glycemic category. The aim of this study is to evaluate whether N-terminal pro-B natriuretic peptide (NT-ProBNP) could help identify subjects at higher cardiovascular risk, independently of blood glucose levels. METHODS: Serum NT-ProBNP levels were measured in 5502 people aged 45-79 years without heart failure from the general population (3380 with normoglycemia, 1125 with pre-diabetes and 997 with diabetes) that participated in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. We applied Cox and Fine Gray models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP levels and all-cause and cardiovascular mortality through December 2015. RESULTS: After a median follow-up of 13 years, 1509 participants died, 330 of cardiovascular causes. In the multivariable-adjusted models, compared with participants with NT-ProBNP < 100 pg/ml, those with levels 100-300 pg/ml and ≥ 300 pg/ml had a higher incidence of both all-cause mortality (HR 1.61, 95% CI 1.12-2.32, p = 0.012 and HR 2.96, 95% CI 1.75-5.00, p < 0.001, respectively) and cardiovascular mortality (HR 1.57, 95% CI 1.17-2.10, p = 0.011 and HR 2.08, 95% CI 1.47-2.93, p < 0.001, respectively). The association was consistent in subgroup analyses based on glycemic status, obesity, age and sex. CONCLUSIONS: Elevated NT-ProBNP is independently associated with all-cause and cardiovascular mortality in the general population and could help identify patients at the highest risk. Further studies are needed to evaluate whether intensification of treatment based on biomarker data might lead to improvements in cardiovascular risk reduction.

Twenty-year trends in heart failure among U.S. adults, 1999-2018: The growing impact of obesity and diabetes.

BACKGROUND: The aim of this study is to evaluate trends in heart failure (HF) prevalence, impact of accompanying risk factors and use of effective therapeutic regimens during the last two decades in the general adult US population. METHODS: We analyzed data obtained from the 1999-2018 cycles of the National Health and Nutrition Examination Survey (NHANES). Among a total of 34,403 participants 40 years or older who attended the mobile examination center visit, 1690 reported a diagnosis of HF. Trends in participant features across calendar periods were assessed by linear regression for continuous variables and logistic regression for binary variables. RESULTS: Prevalence of self-reported HF did not change significantly from 1999 to 2002 to 2015-2018 (~3.5%), while obesity and diabetes showed a progressive increase in prevalence, affecting ~65% and ~ 45% of patients with HF in the most recent calendar period, respectively. In parallel, use of glucose lowering drugs (especially metformin and insulin) as well as statins increased from 1999 to 2010, with significant improvement of the lipid control. A modest improvement in blood pressure control was achieved in association with a significant increase in the use of angiotensin receptor blockers and beta-blockers. CONCLUSIONS: In the last 20 years, the prevalence of HF in US adults remained stable, while both obesity and diabetes increased, with the two conditions affecting half of patients with HF. Improvements in the control of dyslipidemia and, to a lesser extent, blood pressure, was detected; nonetheless, a significant gap remains in guideline-directed use of HF and diabetes medications.

Sex-related association of nonalcoholic fatty liver disease and liver fibrosis with body fat distribution in the general US population.

BACKGROUND: Few population-based studies have investigated the association between body fat distribution and the risk of nonalcoholic fatty liver disease (NAFLD) and significant liver fibrosis. OBJECTIVES: We aimed to evaluate the relations of total body fat and body fat distribution with NAFLD in the general US population. METHODS: This is a cross-sectional, population-based study based on the 2017-2018 cycle of the NHANES. Participants aged 18-59 y without known liver conditions or significant alcohol consumption were studied by DXA and vibration-controlled transient elastography to assess body composition and liver steatosis and fibrosis, respectively. Multivariable logistic regression analysis was performed to evaluate the contribution of BMI and android:gynoid ratio (A:G ratio) to the prevalence of liver steatosis and fibrosis in males and females. RESULTS: Weighted prevalence of steatosis was 41.5% and 29.9% among the 1115 males and 1113 females included in the study, respectively, whereas 7.0% of males and 4.0% of females had elastographic evidence of significant liver fibrosis. After adjustment for age, race-Hispanic origin, diabetes, cigarette smoke, and BMI, a higher A:G ratio was associated with increased odds of steatosis in both males (OR: 1.79; 95% CI: 1.07, 2.99; P = 0.029) and females (OR: 1.95; 95% CI: 1.11, 3.41; P = 0.023). Conversely, a significant association between A:G ratio and liver fibrosis was identified in females (OR: 2.09; 95% CI: 1.11, 3.97; P = 0.026), but not in males (OR: 0.56; 95% CI: 0.29, 1.08; P = 0.078). CONCLUSIONS: Independently from BMI, an android fat deposition pattern is associated with increased prevalence of NAFLD in both sexes, whereas the effect on fibrosis was only evident in females.

Nonalcoholic Fatty Liver Disease, Liver Fibrosis and Cardiovascular Disease in the Adult US Population.

Background: Cardiovascular disease (CVD) risk is higher in patients with nonalcoholic fatty liver disease (NAFLD). Aim: To evaluate whether this can be attributed to the link between NAFLD and known CVD risk factors or to an independent contribution of liver steatosis and fibrosis. Methods: This is an analysis of data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey. We included participants older than 40 years with available data on vibration-controlled transient elastography (VCTE) and without viral hepatitis and significant alcohol consumption. Steatosis and fibrosis were diagnosed by the median value of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. History of CVD was self-reported and defined as a composite of coronary artery disease and stroke/transient ischemic attacks. Results: Among the 2734 included participants, prevalence of NAFLD was 48.6% (95% CI 45.1-51.4), 316 participants (9.7%, 95% CI 8.1-11.6) had evidence of significant liver fibrosis and 371 (11.5%, 95% CI 9.5-13.9) had a history of CVD. In univariate analysis, patients with CVD had a higher prevalence of steatosis (59.6% vs 47.1%, p=0.013), but not fibrosis (12.9% vs 9.3%, p=0.123). After adjustment for potential confounders in a multivariable logistic regression model, neither steatosis nor significant fibrosis were independently associated with CVD and heart failure. Conclusions: In this population-based study, we did not identify an independent association between steatosis and fibrosis and CVD. Large prospective cohort studies are needed to provide a more definitive evidence on this topic.

Seasonal variation in estimated cardiovascular risk in patients with type 2 diabetes.

BACKGROUND AND AIMS: Seasonal variations in several risk factors for cardiovascular events (CVD) were described. Here, we evaluate the impact of seasonal variations in blood pressure (BP), lipid profile and glycemic control on estimated CVD risk in patients with type 2 diabetes (T2D). METHODS AND RESULTS: Retrospective monocentric study of patients with T2D who were visited at least once in the winter period and once in the summer period, less than 8 months apart, for which data related to systolic (S) BP, diastolic (D) BP, body mass index, glycosylated hemoglobin (HbA1c), total cholesterol, HDL cholesterol and smoking habit were available on both occasions. The 10-year CVD risk was calculated using the UKPDS risk engine and the ASCVD risk estimator. As many as 411 patients were included in the study. Significant within-patient differences between summer and winter were found for the absolute risk of events assessed with both calculators (Δs-w UKPDS-CHD: -1.33%, Δs-w UKPDS-Stroke: -0.84%, Δs-w ASCVD: -2.21%). The seasonal change in SBP was the main responsible for the change in risk estimated with both the UKPDS-Stroke (r2 = 0.43) and the ASCVD (r2 = 0.50) scores, while the change in total cholesterol was the main determinant of the change in risk for the UKPDS-CHD (r2 = 0.34). A significant correlation was identified between changes in temperature and changes in SBP (ρ = 0.130, p = 0.008), but not in other risk factors. CONCLUSIONS: Seasonal variations in the classic CVD risk factors influence the risk estimated using validated calculators.

Metabolic and Psychological Features are Associated with Weight Loss 12 Months After Sleeve Gastrectomy.

CONTEXT: Laparoscopic sleeve gastrectomy (LSG) is a recognized effective procedure of bariatric surgery, but a poor response in weight loss may still represent a clinical problem. To date there are no validated predictors useful to better perform patient selection. OBJECTIVE: To establish the association of baseline anthropometric, metabolic, and psychologic features with the percent total weight loss (%TWL) and percent excess weight loss (%EWL) 12 months after surgery. DESIGN: Retrospective longitudinal analysis of a set of data about obese patients attending the outpatient service of a single obesity center from June 2016 to June 2019. PATIENTS: A total of 106 obese patients underwent LSG with presurgery evaluation and follow-up at 12 months after surgery. MAIN OUTCOME: Weight loss 12 months after LSG. RESULTS: Patients who achieved a %TWL higher than the observed median (≥34%) were younger, with a lower fasting plasma glucose and glycated hemoglobin, with a lower prevalence of hypertension and with a lower score in the impulsiveness scale, compared with patients with a %TWL < 34%. Similar findings were found when %EWL was considered. Multivariable stepwise regression analysis showed that younger age, lower impulsiveness, higher-than-normal urinary free cortisol, and lower HbA1c were associated with higher %TWL, explaining about 31.5% of the weight loss. CONCLUSION: Metabolic and psychologic features at baseline were independently associated with weight loss and explained a non-negligible effect on the response to LSG. These data suggest that careful metabolic and psychologic profiling could help in sharper indications and personalized pre- and postsurgical follow-up protocols in candidates for LSG.

Baseline TSH levels and short-term weight loss after different procedures of bariatric surgery.

BACKGROUND: Bariatric surgery is a valuable therapeutic option in the treatment of obesity but the outcomes show a large subject-to-subject variability yet to be explained. Thyroid function may represent an involved factor and we have only few controversial data about its influence. SUBJECTS/METHODS: We retrospectively assessed using a longitudinal approach the relation between baseline TSH levels and short-term (6 and 12 months) weight loss in 387 euthyroid patients who underwent laparoscopic gastric banding (LAGB; n = 187) or sleeve gastrectomy (SG; n = 200). RESULTS: After LAGB, patients with low-normal TSH levels (0.40-1.40 mUI/L) had higher percent total weight loss, ∆BMI and percent excess weight loss when compared to patients with normal (1.41-2.48 mUI/L) and high-normal (2.49-4.00 mUI/L) TSH (p < 0.05). Conversely, no association was detected after SG (p = 0.17). The multivariable regression analysis showed that also baseline BMI (6-12 months) and HOMA2-IR (only at 6 months) were independently associated with the outcomes. CONCLUSIONS: TSH levels may influence the short-term weight loss response after LAGB. The lack of association after SG suggests that the influence of baseline endocrine and metabolic factors may not be relevant for procedures with greater and more immediate calorie intake restriction.

Renal protection: a leading mechanism for cardiovascular benefit in patients treated with SGLT2 inhibitors.

Initially developed as glucose-lowering drugs, sodium-glucose co-transporter type 2 inhibitors (SGLT2i) have demonstrated to be effective agents for the risk reduction of cardiovascular (CV) events in patients with type 2 diabetes mellitus (T2DM). Subsequently, data has emerged showing a significant CV benefit in patients treated with SGLT2i regardless of diabetes status. Renal protection has been initially evaluated in CV randomized trials only as secondary endpoints; nonetheless, the positive results gained have rapidly led to the evaluation of nephroprotection as primary outcome in the CREDENCE trial. Different renal and vascular mechanisms can account for the CV and renal benefits enlightened in recent literature. As clinical guidelines rapidly evolve and the role of SGLT2i appears to become pivotal for CV, T2DM, and kidney disease management, in this review, we analyze the renal effects of SGLT2, the benefits derived from its inhibition, and how this may result in the multiple CV and renal benefits evidenced in recent clinical trials.

Hypercortisolism and altered glucose homeostasis in obese patients in the pre-bariatric surgery assessment.

AIMS: Hypothalamus-pituitary-adrenal (HPA) axis hyperactivity was suggested to be associated with the metabolic syndrome (MS), obesity and diabetes. The aim of this study was to test whether hypercortisolism was associated with altered glucose homeostasis and insulin resistance, hypertension and dyslipidemia in a homogeneous population of obese patients. MATERIALS/METHODS: In retrospective analysis of a set of data about obese patients attending the outpatient service of a single obesity centre between January 2013 and January 2020, 884 patients with BMI >30 kg/m2 were segregated in two subgroups: patients with urinary free cortisol (UFC) higher than normal (UFC+; n = 129) or within the normal range (UFC-; n = 755). RESULTS: The overall prevalence of UFC+ was 14.6% and double test positivity (morning cortisol >1.8 mcg/dL following overnight dexamethasone suppression test, ODST) was detected in 1.0% of patients. Prediabetes (OR 1.74; 95%CI 1.13-2.69; p = 0.012) and diabetes (OR 2.03; 95%CI 1.21-3.42; p = 0.008) were associated with higher risk of UFC+ when analysis was adjusted for confounding variables. Conversely, hypertension and dyslipidemia were not related to UFC+. Within the individuals with normal FPG and HbA1c, those with higher estimated insulin resistance (HOMA2-IR) maintained a higher risk of UFC+ (OR 2.84, 95%CI 1.06-7.63; p = 0.039) and this relationship was weakened only when the body fat percentage was included into the model. CONCLUSIONS: In obese patients, hypercortisolism was more frequent across the entire spectrum of altered glucose homeostasis including the very early stages; this relation could not be detected for the other criteria of the MS, as waist, hypertension and atherogenic dyslipidemia.

Risk stratification tools for heart failure in the diabetes clinic.

The advent of Sodium Glucose Transporter 2-inhibitors (SGLT2-i) in recent years gave endocrinologists the opportunity to actively treat and prevent heart failure (HF) in patients with type 2 diabetes (T2DM). While the relationship between T2DM and HF has been extensively reviewed, previous works focused mostly on epidemiology, pathophysiology and treatment of HF in T2DM. The aim of our work was to aid health care professionals in identifying individuals at high risk for this dreadful complication. Recent guidelines recommend to use drugs with proven cardiovascular benefits (Glucagon-like peptide-1 receptor agonists (GLP1-RA) and SGLT2-i) in patients with previous cardiovascular disease (CVD) and to prefer SGLT2-i in patients with known HF. In everyday clinical practice, the choice between these two drug classes in patients without known HF or atherosclerotic CVD is mostly arbitrary and based on the side effect profile. Recently, risk stratification tools to estimate HF incidence have been developed in order to guide treatment with a view to bring precision medicine into diabetes care. With this purpose, we provide a review of the tools able to predict HF incidence for patients in primary CVD prevention as well as risk of future hospitalizations for patients with known HF.

Visit-to-visit blood pressure variability in patients with type 2 diabetes with and without previous history of cardiovascular disease.

OBJECTIVE: Visit-to-visit variability in SBP is a risk factor for cardiovascular disease (CVD) in type 2 diabetes (T2DM) but little is known on whether in T2DM this differs according to presence or absence of previous CVD. METHODS: We retrospectively assessed the coefficient of variation (standard deviation/mean) of mean SBP (SBP-CV) in 970 patients (44% with established CVD) attending at least four times our secondary care diabetes clinic in 2015-2016 to estimate their risk of CVD-related events using the 10-year UKPDS Risk Engine. RESULTS: Patients with established CVD had a higher SBP-CV (10.3 ±â€Š4.8%) than patients without CVD (8.9 ±â€Š4.3%; P < 0.001) as confirmed by the progressively higher prevalence of established CVD in tertiles of SBP-CV (36.6, 46.1, and 52.0%; P < 0.001), in association with more aggressive and complex drug regimens. On the basis of the 10-year UKPDS Risk Engine, higher SBP-CV values were associated with increased risks of the CVD outcomes regardless of the previous history of CVD in multivariate models. CONCLUSION: Visit-to-visit variability of SBP was greater in T2DM patients with that in those without previous history of CVD, and maintained an independent association with higher estimated risk of CVD-related events regardless of the history of CVD, suggesting that its prognostic significance is relevant in the entire CVD continuum of patients with T2DM.

Resting Energy Expenditure in Obese Women with Primary Hypothyroidism and Appropriate Levothyroxine Replacement Therapy.

CONTEXT: Growing evidence suggests that appropriate levothyroxine (LT4) replacement therapy may not correct the full set of metabolic defects afflicting individuals with hypothyroidism. OBJECTIVE: To assess whether obese subjects with primary hypothyroidism are characterized by alterations of the resting energy expenditure (REE). DESIGN: Retrospective analysis of a set of data about obese women attending the outpatients service of a single obesity center from January 2013 to July 2019. PATIENTS: A total of 649 nondiabetic women with body mass index (BMI) > 30 kg/m2 and thyrotropin (TSH) level 0.4-4.0 mU/L were segregated into 2 groups: patients with primary hypothyroidism taking LT4 therapy (n = 85) and patients with normal thyroid function (n = 564). MAIN OUTCOMES: REE and body composition assessed using indirect calorimetry and bioimpedance. RESULTS: REE was reduced in women with hypothyroidism in LT4 therapy when compared with controls (28.59 ±â€…3.26 vs 29.91 ±â€…3.59 kcal/kg fat-free mass (FFM)/day), including when adjusted for age, BMI, body composition, and level of physical activity (P = 0.008). This metabolic difference was attenuated only when adjustment for homeostatic model assessment of insulin resistance (HOMA-IR) was performed. CONCLUSIONS: This study demonstrated that obese hypothyroid women in LT4 therapy, with normal serum TSH level compared with euthyroid controls, are characterized by reduced REE, in line with the hypothesis that standard LT4 replacement therapy may not fully correct metabolic alterations related to hypothyroidism. We are not able to exclude that this feature may be influenced by the modulation of insulin sensitivity at the liver site, induced by LT4 oral administration.

Screening for non-alcoholic fatty liver disease in type 2 diabetes using non-invasive scores and association with diabetic complications.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is prevalent in patients with type 2 diabetes. Here, we estimate the proportion of patients with type 2 diabetes that should be referred to hepatologists according to the European Association for the Study of the Liver (EASL)-European Association for the Study of Diabetes (EASD)-European Association for the Study of Obesity (EASO) Guidelines and evaluate the association between non-invasive biomarkers of steatosis and fibrosis and diabetic complications. RESEARCH DESIGN AND METHODS: This is a retrospective analysis of type 2 diabetes patients who attended on a regular basis our diabetes clinic between 2013 and 2018 (n=2770). Steatosis was assessed using Fatty Liver Index (FLI), Hepatic Steatosis Index and NAFLD Ridge Score and fibrosis using NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI) and AST/alanine aminotransferase (ALT) ratio. Outcome measures were altered albumin excretion rate (AER), chronic kidney disease (CKD) and cardiovascular disease (CVD). RESULTS: The prevalence of advanced fibrosis varied from 1% (APRI) to 33% (NFS). The application of the guidelines using a sequential combination of FLI and FIB-4 would lead to referral of 28.3% of patients when using standard FIB-4 cut-offs, while this number dropped to 13.4% when age-adjusted FIB-4 thresholds were applied. A higher prevalence of altered AER was associated with liver steatosis (FLI: OR: 3.49; 95% CI 2.05 to 5.94, p<0.01), whereas liver fibrosis was associated with CKD (FIB-4: OR: 6.39; 95% CI 4.05 to 10.08, p<0.01) and CVD (FIB-4: OR: 2.62; 95% CI 1.69 to 4.04, p<0.01). CONCLUSIONS: While specific fibrosis scores identify different proportion of patients with advanced fibrosis, the use of age-adjusted FIB-4 cut-offs leads to a drop in gray-zone results, making referrals to hepatologists more sustainable. Interestingly non-invasive biomarkers were consistently associated with a different pattern of diabetic complications.