Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing rapidly. It is nowadays recognized as the most frequent liver disease, affecting a quarter of global population and regularly coexisting with metabolic disorders such as type 2 diabetes, hypertension, obesity, and cardiovascular disease. In a more simplistic view, NAFLD could be defined as an increase in liver fat content, in the absence of secondary cause of steatosis. In fact, the clinical onset of the disease is a much more complex process, closely related to insulin resistance, limited expandability and dysfunctionality of adipose tissue. A fatty liver is a main driver for a new recognized liver-pancreatic α-cell axis and increased glucagon, contributing to diabetes pathophysiology. Main text: This review will focus on the clinical and pathophysiological connections between NAFLD, insulin resistance and type 2 diabetes. We reviewed non-invasive methods and several scoring systems for estimative of steatosis and fibrosis, proposing a multistep process for NAFLD evaluation. We will also discuss treatment options with a more comprehensive view, focusing on the current available therapies for obesity and/or type 2 diabetes that impact each stage of NAFLD. Conclusion: The proper understanding of NAFLD spectrum-as a continuum from obesity to metabolic syndrome and diabetes-may contribute to the early identification and for establishment of targeted treatment.

BackgroundSince the first position statement on diabetes and cardiovascular prevention published in 2014 by the Brazilian Diabetes Society, the current view on primary and secondary prevention in diabetes has evolved as a result of new approaches on cardiovascular risk stratification, new cholesterol lowering drugs, and new anti-hyperglycemic drugs. Importantly, a pattern of risk heterogeneity has emerged, showing that not all diabetic patients are at high or very high risk. In fact, most younger patients who have no overt cardiovascular risk factors may be more adequately classified as being at intermediate or even low cardiovascular risk. Thus, there is a need for cardiovascular risk stratification in patients with diabetes. The present panel reviews the best current evidence and proposes a practical risk-based approach on treatment for patients with diabetes.Main bodyThe Brazilian Diabetes Society, the Brazilian Society of Cardiology, and the Brazilian Endocrinology and Metabolism Society gathered to form an expert panel including 28 cardiologists and endocrinologists to review the best available evidence and to draft up-to-date an evidence-based guideline with practical recommendations for risk stratification and prevention of cardiovascular disease in diabetes. The guideline includes 59 recommendations covering: (1) the impact of new anti-hyperglycemic drugs and new lipid lowering drugs on cardiovascular risk; (2) a guide to statin use, including new definitions of LDL-cholesterol and in non-HDL-cholesterol targets; (3) evaluation of silent myocardial ischemia and subclinical atherosclerosis in patients with diabetes; (4) hypertension treatment; and (5) the use of antiplatelet therapy.ConclusionsDiabetes is a heterogeneous disease. Although cardiovascular risk is increased in most patients, those without risk factors or evidence of sub-clinical atherosclerosis are at a lower risk. Optimal management must rely on an approach that will cover both cardiovascular disease prevention in individuals in the highest risk as well as protection from overtreatment in those at lower risk. Thus, cardiovascular prevention strategies should be individualized according to cardiovascular risk while intensification of treatment should focus on those at higher risk.

Objective: Mutations in LMNA have been linked to diverse disorders called laminopathies, which display heterogeneous phenotypes and include diseases affecting muscles, axonal neurons, progeroid syndromes, and lipodystrophies. Among the lipodystrophies, LMNA mutations have been reported most frequently in patients with familial partial lipodystrophy (FPLD) of the Dunnigan variety; however, phenotypic heterogeneity in the pattern of body fat loss has been observed. In this study, we searched for LMNA mutations in patients with various forms of lipodystrophy. Design and methods: We studied 21 unrelated individuals with lipodystrophy. Subjects underwent a complete clinical evaluation and were classified as typical FPLD (nZ12), atypical partial lipodystrophy (nZ7), or generalized lipodystrophy (nZ2). Molecular analysis of LMNA gene, analysis of body fat by dual-energy X-ray absorptiometry, and biochemical measurements were performed.

Patients with the heterozygous LMNA p.T10I mutation have distinct clinical features and significantly worse metabolic complications compared with other patients with APS as well as patients with Hutchinson-Gilford progeria syndrome. We propose that they be recognized as having generalized lipodystrophy-associated progeroid syndrome. Patients with generalized lipodystrophy-associated progeroid syndrome should undergo careful multisystem assessment at onset and yearly metabolic and cardiac evaluation, as hyperglycemia, hypertriglyceridemia, hepatic steatosis, and cardiomyopathy are the major contributors to morbidity and mortality.

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 = −0.54; P = 0.004), 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.

BackgroundFamilial partial lipodystrophies (FPLD) are clinically heterogeneous disorders characterized by selective loss of adipose tissue, insulin resistance and metabolic complications. Until genetic studies become available for clinical practice, clinical suspicion and pattern of fat loss are the only parameters leading clinicians to consider the diagnosis. The objective of this study was to compare body composition by dual energy X-ray absorptiometry (DXA) in patients with FPLD and control subjects, aiming to find objective variables for evaluation of FPLD.MethodsEighteen female patients with partial lipodystrophy phenotype and 16 healthy controls, matched for body mass index, sex and age were studied. All participants had body fat distribution evaluated by DXA measures. Fasting blood samples were obtained for evaluation of plasma leptin, lipid profile and inflammatory markers. Genetic studies were carried out on the 18 patients selected that were included for statistical analysis. Thirteen women confirmed diagnosis of Dunnigan-type FPLD (FPLD2).ResultsDXA revealed a marked decrease in truncal fat and 3 folds decrease in limbs fat percentage in FPLD2 patients (p <0.001). Comparative analysis showed that ratio between trunk and lower limbs fat mass, characterized as Fat Mass Ratio (FMR), had a greater value in FLPD2 group (1.86 ± 0.43 vs controls 0.93 ± 0.10; p <0.001) and a improved accuracy for evaluating FPLD2 with a cut-off point of 1.2. Furthermore, affected women showed hypoleptinemia (FLPD2 4.9 ± 2.0 vs controls 18.2 ± 6.8; p <0.001), insulin resistance and a more aggressive lipid profile.ConclusionIn this study, assessment of body fat distribution by DXA permitted an objective characterization of FLPD2. A consistent pattern with marked fat reduction of lower body was observed in affected patients. To our knowledge this is the first time that cut-off values of objective variables were proposed for evaluation of FPLD2.

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BackgroundDipeptidyl peptidase-4 (DDP4) is an enzyme responsible for glucagon-like peptide-1 inactivation and plays an important role in glucose metabolism.ObjectiveThe aim of this study was to evaluate DPP4 levels in patients with familial partial lipodystrophy type 2 (FPLD2) and correlate it with body fat distribution.MethodsFourteen patients with FPLD2 were selected to participate in this study and matched to a healthy control group (n = 8). All participants had anthropometrical data registered. Body adiposity index (BAI) was used to evaluate fat distribution in this population. Body fat content and distribution were analyzed by dual X-ray absorptiometry (DXA). Biochemical exams, including DPP4 levels, were performed in all individuals.ResultsDespite the same body mass index, lipodystrophic patients had a significant lower hip (median 92.0 vs 94.5; p = 0.028), HDL cholesterol (42.6 ± 10.4 vs 66.1 ± 16.0; p < 0.01) and BAI (24.1 ± 2.8 vs 29.0 ± 3.7; p = 0.02), suggesting that BAI was able to catch differences in fat distribution between groups. On the other hand, patients with FPLD2 presented significant higher levels of insulin (median 11.2 vs 5.3; p = 0.015), triglycerides (184.9 ± 75.4 vs 89.1 ± 51.0; p < 0.01) and DPP4 (4.89 ± 0.92 vs 3.93 ± 1.08; p = 0.04). A trend toward an inverse statistical significance was observed between DPP4 levels and BAI (r = −0.38; p = 0.072). In the lipodistrophic group, a significant correlation was found between DPP4 levels and percentage of total body fat (r = 0.86; p = 0.0025) and android fat (r = 0.78; p = 0.014).ConclusionsPatients with FPLD2 exhibit an increase in DDP4 levels in comparison to a healthy control group. The increase in the levels of this enzyme does not seem to be related to the diagnosis of diabetes and might be associated with an increase in central fat (estimated using BAI and measured using DXA). These results might be used to reinforce the concept that DDP4 is an adipokine related to central fat distribution.