Waist circumference is independently associated with liver steatosis and fibrosis in LMNA-related and unrelated Familial Partial Lipodystrophy women.

BACKGROUND: Lipodystrophies are a heterogeneous group of diseases characterized by the selective loss of subcutaneous adipose tissue and ectopic fat deposition in different organs, including the liver. This study aimed to determine the frequencies of liver steatosis (LS) and liver fibrosis (LF) in a sample of individuals with LMNA-related and unrelated Familial Partial Lipodystrophy. METHODS: This cross-sectional study included 17 women with LMNA-related FPLD and 15 women with unrelated FPLD. LS and LF were assessed using transient elastography (TE) with FibroScan®. Anthropometric and biochemical variables were included in a multiple linear regression analysis to identify the variables that were independently related to liver disease. RESULTS: Regarding the presence of LF, 22 (68.2%) women were classified as having non-significant fibrosis, and 10 (31.8%) were classified as having significant or severe fibrosis. Regarding LS, only six women (20.7%) were classified as having an absence of steatosis, and 23 (79.3%) had mild to severe steatosis. After multiple linear regression, waist circumference (but not age, body mass index, or waist-to-hip ratio) was found to be independently related to LS and LF. Among the biochemical variables, only triglyceride levels were independently related to LS but not LF. CONCLUSIONS: In women with FPLD, visceral fat accumulation appears to be the most important determinant of liver disease, including LF, rather than fat scarcity in the lower limbs.

Determinants of glycemic control in type 2 diabetes mellitus in Brazil: A sub-analysis of the longitudinal data from the BrazIian type 1 & 2 diabetes disease registry (BINDER).

BACKGROUND: Data on glycemic control and its determinants among Brazilian patients with type-2 diabetes (DM2) are scarce. The BrazIliaN Type 1 & 2 DiabetEs Disease Registry (BINDER) is a multicenter, longitudinal study, designed to investigate the glycemic control in a real-word scenario. METHODS: 1142 patients participated in the five visits of the BINDER study between April/2017 and October/2019. For each visit, glycemic control was assessed using the last measure available for HbA1c. Sociodemographic and anthropometric characteristics were also analyzed. RESULTS: At baseline, the median HbA1c level was 7.1% (4.1-15.0%); 259 (31.4%) participants had HbA1c ≤ 6.5% and 396 (48.2%) had HbA1c ≤ 7.0%. Younger age (p = 0.014), low educational level (p = 0.025) and the type of healthcare service (public sector; p = 0.0058) were independently associated with the elevated HbA1c. After 2 years, there were no statistically significant differences in HbA1c median values in relation to baseline. CONCLUSIONS: In this sample of DM2 patients, younger age, low educational level and being treated at the public service were associated with worse glycemic control. Over a 2-year follow-up, there was no significant change in the median HbA1c. These findings suggest that strategies are needed to improve glycemic control, especially in those treated in the public service.

Proposal of an obesity classification based on weight history: an official document by the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO).

Obesity is a chronic disease associated with impaired physical and mental health. A widespread view in the treatment of obesity is that the goal is to normalize the individual's body mass index (BMI). However, a modest weight loss (usually above 5%) is already associated with clinical improvement, while weight losses of 10%-15% bring even further benefits, independent from the final BMI. The percentage of weight reduction is accepted as a treatment goal since a greater decrease in weight is frequently difficult to achieve due to metabolic adaptation along with environmental and lifestyle factors. In this document, the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO) propose a new obesity classification based on the maximum weight attained in life (MWAL). In this classification, individuals losing a specific proportion of weight are classified as having "reduced" or "controlled" obesity. This simple classification - which is not intended to replace others but to serve as an adjuvant tool - could help disseminate the concept of clinical benefits derived from modest weight loss, allowing individuals with obesity and their health care professionals to focus on strategies for weight maintenance instead of further weight reduction. In future studies, this proposed classification can also be an important tool to evaluate possible differences in therapeutic outcomes between individuals with similar BMIs but different weight trajectories.

Proposal of an obesity classification based on weight history: an official document by the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO)

ABSTRACT Obesity is a chronic disease associated with impaired physical and mental health. A widespread view in the treatment of obesity is that the goal is to normalize the individual's body mass index (BMI). However, a modest weight loss (usually above 5%) is already associated with clinical improvement, while weight losses of 10%-15% bring even further benefits, independent from the final BMI. The percentage of weight reduction is accepted as a treatment goal since a greater decrease in weight is frequently difficult to achieve due to metabolic adaptation along with environmental and lifestyle factors. In this document, the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO) propose a new obesity classification based on the maximum weight attained in life (MWAL). In this classification, individuals losing a specific proportion of weight are classified as having "reduced" or "controlled" obesity. This simple classification - which is not intended to replace others but to serve as an adjuvant tool - could help disseminate the concept of clinical benefits derived from modest weight loss, allowing individuals with obesity and their health care professionals to focus on strategies for weight maintenance instead of further weight reduction. In future studies, this proposed classification can also be an important tool to evaluate possible differences in therapeutic outcomes between individuals with similar BMIs but different weight trajectories.

Pancreatic fat deposition is increased and related to beta-cell function in women with familial partial lipodystrophy.

BACKGROUND: To study pancreatic fat deposition and beta-cell function in familial partial lipodystrophy (FPLD) patients. METHODS: In a cross-sectional study, eleven patients with FPLD, and eight healthy volunteers were matched for age and body mass index and studied at a referral center. Body composition was assessed using dual-energy X-ray absorptiometry and the Dixon method of magnetic resonance imaging was used to quantify pancreatic and liver fat. Fasting plasma glucose, insulin, leptin, lipids and homeostasis model assessment of insulin resistance values were measured, and an oral glucose tolerance test was performed. The insulinogenic index, Matsuda insulin sensitivity index and beta-cell disposition index were calculated. RESULTS: The FPLD group presented a higher waist-to-hip ratio and fat mass ratio and lower total, truncal and lower-limb fat masses. Pancreatic and liver fat contents (log transformed) were significantly higher in the FPLD group (5.26 ± 1.5 vs. 4.08 ± 0.64, p = 0.034 and 0.77 ± 0.50 vs. 0.41 ± 0.18, p = 0.056, respectively). Pancreatic fat was inversely related to the DI (r = - 0.53, p = 0.027) and HDL-cholesterol (r = - 0.63, p = 0.003) and directly related to WHR (r = 0.60; p = 0.009), HbA1c (r = 0.58; p = 0.01) and serum triglyceride (r = 0.48, p = 0.034). Higher triglyceride and lower HDL-cholesterol levels were observed in the FPLD group. CONCLUSIONS: This study demonstrated for the first time that pancreatic fat deposition is increased in FPLD. Moreover, an inverse relationship was demonstrated between pancreatic fat and beta-cell function. The findings of this study may be consistent with the expandability hypothesis and the twin cycle hypothesis.

Avaliação da frequência de deficiência de vitamina D em pacientes com obesidade / Evaluation of the frequency of vitamin D deficiency in patients with obesity

Introdução: A obesidade é um problema de saúde pública mundial. Além das diversas alterações metabólicas encontradas em indivíduos obesos, há evidências de alterações no sistema endócrino, como observado no metabolismo da vitamina D. Objetivo: Avaliar a frequência de deficiência de vitamina D em uma amostra de pacientes adultos com obesidade. Material e métodos: Foi realizado um estudo transversal retrospectivo analisando 183 prontuários dos pacientes atendidos pela primeira vez buscando tratamento para obesidade. Após os fatores de exclusão, restaram 113 prontuários válidos. Resultados: O IMC variou de 30.1 a 77.1, com uma mediana de 44.5 kg/m2. Trinta pacientes (26,55 %) tinham a Vitamina D abaixo de 20 ng/ml, sendo considerados com diagnóstico de Deficiência de Vitamina D. Nenhuma correlação foi encontrada entre os níveis de Vitamina D e os parâmetros antropométricos. Houve associação significativa estatística dos níveis de Vitamina D com colesterol total (r=-0.26; p=0.0053), LDL-colesterol (r=-0.25; p=0.0071), além de uma tendência à significância com os níveis de TGP (r=0.16; p=0.088). Conclusão: Houve uma elevada frequência de deficiência de vitamina D em pacientes obesos. Não houve correlação entre os níveis de vitamina D e os marcadores antropométricos, porém foi encontrada uma correlação inversa de vitamina D com níveis de colesterol total e LDL-colesterol, mostrando a relação com a dislipidemia. Também, houve uma tendência à significância com os níveis de TGP, o que provavelmente remete à esteatose hepática, comum em obesos.

Introduction: Obesity is a global public health problem. In addition to the various metabolic alterations found in obese individuals, there is evidence of alterations in the endocrine system, as observed in vitamin D metabolism. Objective: To evaluate the frequency of vitamin D deficiency in a sample of adult patients with obesity. Material and methods: A retrospective cross-sectional study was carried out analyzing 183 medical charts of who seek treatment for obesity. After exclusion factors, there were 113 valid medical records. Results: The BMI ranged from 30.1 to 77.1, with a median of 44.5 kg / m2. Thirty patients (26.55%) had Vitamin D below 20 ng/ml, being considered as vitamin D deficiency. No correlation was found between vitamin D and anthropometric parameters. There was a statistically significant association of hypovitaminosis D with total cholesterol (r = -0.26, p = 0.0053), LDL cholesterol (r = -0.25, p = 0.0071), and a trend towards significance with TGP levels (r = 0.16; p = 0.088). Conclusion: There was an increased frequency of vitamin D deficiency in obese individuals. There was no correlation between vitamin D levels and anthropometric markers, but an inverse correlation of vitamin D with total and LDL-cholesterol levels was found, showing the relation with dyslipidemia. Also, there was a trend toward significance with TGP levels, which probably refers to hepatic steatosis, common in obese patients.

Impact of a 6-month treatment with intragastric balloon on body composition and psychopathological profile in obese individuals with metabolic syndrome.

BACKGROUND: The aim of this study was to investigate the effects of a 6-month treatment with intragastric balloon (IGB) on body composition and depressive/anxiety symptoms in obese individuals with metabolic syndrome (MS). METHODS: Fifty patients (aged 18-50 years) with obesity and MS were selected for treatment with IGB for 6 months. Body composition was verified with dual-energy X-ray absorptiometry (DXA) at baseline and right after IGB removal. Anxiety/depressive symptoms were assessed with the Beck Depression Inventory (BDI) and the hospital anxiety and depression scale (HADS) at baseline and after 6 months of treatment. RESULTS: In total, 39 patients completed the study. After 6 months, there were significant decreases in weight (11.7 ± 9.6 kg, p < 0.0001) and waist circumference (9.3 ± 8.2 cm, p < 0.0001). Weight loss was also demonstrated by DXA and corresponded to decreases of 3.0 ± 3.4% in body fat percentage, 7.53 ± 7.62 kg in total body fat, and 3.70 ± 4.89 kg in lean body mass (p < 0.001 for all comparisons). Depressive symptoms scores decreased by a mean of 4.57 ± 10.6 points when assessed with the BDI (p = 0.002) and 1.82 ± 5.16 points when assessed with the HADS-Depression (p = 0.0345). Anxiety symptoms scores decreased by a mean of 1.84 ± 4.04 points when determined with the HADS-anxiety (p = 0.0066). The decrease in body fat percentage was the parameter that best correlated with improvements in depressive (p = 0.008) and anxiety symptoms (p = 0.014). CONCLUSIONS: In obese individuals with MS, fat mass reduction was associated with short-term improvements in depressive and anxiety symptoms. Trial Registration Registered at ClinicalTrials.gov, NCT01598233.

Is cognitive impairment associated with the presence and severity of peripheral neuropathy in patients with type 2 diabetes mellitus?

BACKGROUND: Peripheral Diabetic Neuropathy (PDN) and cognitive impairment are complications of Diabetes Mellitus (DM) that seem to share several underlying mechanisms. The aim of this study was to investigate whether diabetic patients would have worse cognitive function than non diabetic individuals and within diabetic patients, whether those with PDN would present an even more significant cognitive impairment. FINDINGS: Ninety four (94) outpatients with Type 2 DM were sequentially evaluated. Also, Fifty four (54) healthy individuals were sequentially selected to match the diabetic group. For the assessment of neuropathy, Portuguese versions of the Neuropathy Disability Score (NDS) and Neuropathy Symptom Score (NSS) were used. Global cognitive function was assessed by using the Portuguese Version of the Mini-Mental State Examination (MMSE), Trail Making Tests A and B and Verbal Fluency Test. Significantly lower scores were found in the Type 2 DM group in comparison to control group in the MMSE (25.7 [16-30] vs 27.6 [19-30]; p <0.001). Within T2DM group, forty five (45) patients were diagnosed with PDN. No differences were found between patients with and without PDN in all cognitive tests (p >0.05 in all comparison). No correlation was also found among NSS, NDS and any of the cognitive tests. CONCLUSION: Although diabetic patients do have a worse cognitive function, this impairment does not seem to be related to the presence and/or severity of PDN.

Evaluation of epicardial adipose tissue in familial partial lipodystrophy.

BACKGROUND: Dunnigan type Familial Partial Lipodystrophy (FPLD) is characterized by loss of subcutaneous fat from the limbs and excessive accumulation on the visceral adipose tissue (VAT). Affected individuals have insulin resistance (IR), diabetes, dyslipidemia and early cardiovascular (CV) events, due to their imbalanced distribution of total body fat (TBF). Epicardial adipose tissue (EAT) is correlated with VAT. Hence, EAT could be a new index of cardiac and visceral adiposity with great potential as a marker of CV risk in FPLD. OBJECTIVE: Compare EAT in FPLD patients versus healthy controls. Moreover, we aimed to verify if EFT is related to anthropometrical (ATPM) and Dual-Energy X-ray Absorptiometry (DEXA) measures, as well as laboratory blood findings. We postulated that FPLD patients have enlarged EAT. METHODS: This is an observational, cross-sectional study. Six patients with a confirmed mutation in the LMNA gene for FPLD were enrolled in the study. Six sex, age and BMI-matched healthy controls were also selected. EFT was measured by transthoracic echocardiography (ECHO). All participants had body fat distribution evaluated by ATPM and by DEXA measures. Fasting blood samples were obtained for biochemical profiles and also for leptin measurements. RESULTS: Median EFT was significantly higher in the FPLD group than in matched controls (6.0 ± 3.6 mm vs. 0.0 ± 2.04 mm; p = 0.0306). Additionally, FPLD patients had lower leptin values. There was no significant correlation between EAT and ATPM and DEXA measurements, nor laboratory findings. CONCLUSIONS: This study demonstrates, for the first time, that EAT measured by ECHO is increased in FPLD patients, compared to healthy controls. However, it failed to prove a significant relation neither between EAT and DEXA, ATPM or laboratory variables analyzed.

Body composition and depressive/anxiety symptoms in overweight and obese individuals with metabolic syndrome.

BACKGROUND: Several studies point to a correlation between obesity and the severity of depressive and anxiety symptoms in children and adults, but there are still some controversial points about this association. The aim of this study is to investigate the relationship between body composition and the severity of anxiety/depressive symptoms in overweight and obese individuals with Metabolic Syndrome (MS). METHODS: Fifty patients, 18-50 years old, overweight or obese and with the diagnosis of MS based on the International Diabetes Federation (IDF) criteria were selected for this study. Body composition was evaluated using Dual Energy X-ray Absorptiometry (DXA). Depressive symptoms were evaluated using the Hospital Anxiety and Depression Scale (HADS-Depression) and the Beck Depression Inventory (BDI). Anxiety symptoms were evaluated using HADS-Anxiety. RESULTS: No correlation was found between depressive symptoms (HADS-Depression or BDI) and Body Mass Index (BMI) (r = 0.01; p = 0.94 and r = -0.12, p = 0.38; respectively), Waist Circumference (WC) (r = -0.06, p = 0.67 and r = -0.22, p = 0.12; respectively), and Waist-to-Hip Ratio (WHR) (r = -0.12, p = 0.40 and r = -0.17, p = 0.23; respectively). Additionally, no correlation was found among anxiety symptoms (HADS-Anxiety) and BMI (r = -0.15, p = 0.27), and WHR (r = -0.17, p = 0.24). In contrast, a significant correlation was found between percentage of total fat (DXA) and HADS-Depression (r = 0.34, p = 0.019) and HADS-Anxiety (r = 0.30, p = 0.039). Additionally, an inverse and strong correlation was found between lean mass (in grams) and HADS-Depression (r = -0.42, p = 0.004), HADS anxiety (r = -0.57, p < 0.0001), and BDI (r = -0.44, p = 0.026). CONCLUSIONS: In individuals with MS, the percentage of body fat, and not central fat, BMI, WC, or WHR, was associated with an increased severity of anxiety and depressive symptoms. In contrast, total lean mass was strongly associated with fewer anxiety/depressive symptoms, suggesting that body composition might be related to psychiatric comorbidity in overweight individuals with MS.

Type 2 Diabetes Mellitus and Alzheimer's Disease: from physiopathology to treatment implications.

Alzheimer's Disease (AD) is the most common cause of dementia worldwide. Type 2 Diabetes Mellitus (T2DM) is a disease characterized by insulin resistance (IR) and progressive ß cell failure, and affected individuals are at increased risk to develop several forms of cognitive dysfunction, including AD. Different mechanisms have already been identified linking visceral obesity, IR and AD. Insulin resistance is associated with a decrease in glucose uptake by neurons, an increase in Amyloid ß production and secretion, in the formation of senile plaques, and also in tau protein phosphorylation. Other mechanisms also include a decrease in Insulin Degrading Enzyme (IDE) activity and an increase in oxidative stress secondary to hyperglycemia. Taken together, these mechanisms suggest that drugs used to ameliorate hyperglycemia and IR may also have beneficial effects in diabetic patients with AD. Indeed, manuscripts investigating the effects of metformin, thiazolinediones, leptin, GLP-1 therapies, insulin and bariatric surgery in cognition and AD have been published with very promising results, and may indicate an alternative approach for these patients. This article is protected by copyright. All rights reserved.

A new method for body fat evaluation, body adiposity index, is useful in women with familial partial lipodystrophy.

BMI is a widely used method to evaluate adiposity. However, it has several limitations, particularly an inability to differentiate lean from fat mass. A new method, body adiposity index (BAI), has been recently proposed as a new measurement capable to determine fat excess better than BMI. The aim of this study was to investigate BAI as a mean to evaluate adiposity in a group of women with familial partial lipodystrophy (FPLD) and compare it with BMI. Thirteen women with FLPD Dunnigan type (FPLD2) and 13 healthy volunteers matched by age and BMI were studied. Body fat content and distribution were analyzed by dual X-ray absorptiometry (DXA). Plasma leptin was also measured. BAI was significantly lower in FPLD2 in comparison to control group (24.6 ± 1.5 vs. 30.4 ± 4.3; P < 0.001) and presented a more significant correlation with total fat (%) (r = 0.71; P < 0.001) and fat Mass (g) (r = 0.80; P < 0.001) than BMI (r = 0.27; P = 0.17 for total fat and r = 0.52; P = 0.006 for fat mass). There was a correlation between leptin and BAI (r = 0.57; P = 0.01), [corrected] but not between leptin and BMI. In conclusion, BAI was able to catch differences in adiposity in a sample of FPLD2 patients. It also correlated better with leptin levels than BMI. Therefore, we provide further evidence that BAI may become a more reliable indicator of fat mass content than the currently available measurements.

Depression, glycemic control and type 2 diabetes.

BACKGROUND: Comorbid depression in diabetes has been suggested as one of the possible causes of an inadequate glycemic control. The purpose of this study was to investigate the association between major depression and the glycemic control of type 2 diabetes mellitus (T2DM). METHODS: Seventy T2DM patients were evaluated. They underwent a psychiatric examination using the following instruments: Structured Clinical Interview for DSM-IV and Beck Depression Inventory. The diabetes status was assessed in the short-term (glycemia, glycated hemoglobin) clinical control. RESULTS: The presence of current depression was observed in 18.6% (13/70). In addition, type 2 diabetes patients who displayed depression evidenced higher levels of glycated hemoglobin (8.6 ± 2.0 vs. 7.5 ± 1.8; p = 0.05) when compared to those who did not exhibit a mood disorder. CONCLUSIONS: In our sample, the presence of depression seems to impact on the short-term control of T2DM. The authors discuss the clinical utility of these findings in the usual treatment of diabetes.

Serum retinol binding protein 4 is not decreased in congenital generalized lipodystrophy: a case series.

INTRODUCTION: Previous studies have suggested that Retinol Binding Protein 4 (RPB4), a protein produced by the adipose tissue, is associated with insulin resistance (IR). Congenital Generalized Lipodystrophy (CGL) is a rare disease characterized by IR and paucity of adipose tissue. Our objective was to determine RBP4 levels in patients with CGL. SUBJECTS AND METHODS: Six (6) patients with CGL and a healthy control group were selected to participate in the study. Anthropometric and biochemical variables were compared between groups. RESULTS: No difference was observed in RBP4 levels between the two groups (CGL 42.5 [12.5 - 127] vs. control 57.4 [15.9 - 165]; p = 0.78). On the other hand, leptin levels were significantly lower in CGL patients (CGL 0.65 [0.2 - 0.7] vs. control 10.9 [0.9 - 38.6]; p = 0.015). No correlation was found between RBP-4 and waist circunference (r = 0.18, p = 0.57), or BMI (r = 0.24, p = 0.45). CONCLUSION: RBP4 is not decreased in CGL. These results suggest that adipose tissue may not be the main source of RBP4.

Serum retinol binding protein 4 is not decreased in congenital generalized lipodystrophy: a case series / Os níveis plasmáticos da retinol binding protein 4 (rbP4) não estão reduzidos na lipodistrofia congênita generalizada: uma série de casos

INTRODUCTION: Previous studies have suggested that Retinol Binding Protein 4 (RPB4), a protein produced by the adipose tissue, is associated with insulin resistance (IR). Congenital Generalized Lipodystrophy (CGL) is a rare disease characterized by IR and paucity of adipose tissue. Our objective was to determine RBP4 levels in patients with CGL. SUBJECTS AND METHODS: Six (6) patients with CGL and a healthy control group were selected to participate in the study. Anthropometric and biochemical variables were compared between groups. RESULTS: No difference was observed in RBP4 levels between the two groups (CGL 42.5 [12.5 - 127] vs. control 57.4 [15.9 - 165]; p = 0.78). On the other hand, leptin levels were significantly lower in CGL patients (CGL 0.65 [0.2 - 0.7] vs. control 10.9 [0.9 - 38.6]; p = 0.015). No correlation was found between RBP-4 and waist circunference (r = 0.18, p = 0.57), or BMI (r = 0.24, p = 0.45). CONCLUSION: RBP4 is not decreased in CGL. These results suggest that adipose tissue may not be the main source of RBP4.

INTRODUÇÃO: Estudos prévios sugeriram que os níveis plasmáticos da retinol binding protein (RBP4), uma proteína do tecido adiposo, estão associados com a resistência à insulina (RI). A lipodistrofia congênita generalizada (LCG) é uma doença rara caracterizada por ausência de tecido adiposo e RI. O objetivo é determinar os níveis de RBP4 em pacientes com LCG. SUJEITOS E MÉTODOS: Seis (6) pacientes com LCG e um grupo controle saudável foram selecionados para participar no estudo. As variáveis antropométricas e bioquímicas foram comparadas quando comparados os grupos. RESULTADOS: Nenhuma diferença foi observada entre os níveis de RBP4 log entre os grupos (LCG 42,5 [12,5 - 127] vs. controle 57,4 [15,9 - 165]; p = 0,78). Por outro lado, os níveis de leptina foram menores em pacientes com LCG (LCG 0,65 [0,2 - 0,7] vs. controle 10.9 [0,9 - 38,6]; p = 0,015). Nenhuma correlação foi encontrada entre RBP4 e cintura (r = 0,18, p = 0,57) ou IMC (r = 0,24, p = 0,45). CONCLUSÃO: RBP4 não está diminuída na LCG. Esses resultados sugerem que o tecido adiposo pode não ser a principal fonte de RBP4.