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Background: Familial Partial Lipodystrophy (FPLD) is a disease with wide clinical and genetic variation, with seven different subtypes described. Until genetic testing becomes feasible in clinical practice, non-invasive tools are used to evaluate body composition in lipodystrophic patients. This study aimed to analyze the different anthropometric parameters used for screening and diagnosis of FPLD, such as thigh skinfold thickness (TS), Köb index (Köbi), leg fat percentage (LFP), fat mass ratio (FMR) and leg-to-total fat mass ratio in grams (LTR), by dual-energy X-ray absorptiometry, focusing on determining cutoff points for TS and LFP within a Brazilian population., Methods: Thirty-seven patients with FPLD and seventy-four healthy controls matched for body mass index, sex and age were studied. Data were collected through medical record review after signing informed consent. All participants had body fat distribution evaluated by skinfolds and DXA measures. Fasting blood samples were collected to evaluate glycemic and lipid profiles. Genetic studies were carried out on all patients. Two groups were categorized based on genetic testing and/or anthropometric characteristics: FPLD+ (positive genetic test) and FPLD1 (negative genetic testing, but positive clinical/anthropometric criteria for FPLD)., Results: Eighteen (48.6%) patients were classified as FPLD+, and 19 (51.4%) as FPLD1. Unlike what is described in the literature, the LMNA variant in codon 582 was the most common. Among the main diagnostic parameters of FPLD, a statistical difference was observed between the groups for, Köbi, TS, LFP, FMR, and LTR. A cutoff point of 20 mm for TS in FPLD women was found, which is lower than the value classically described in the literature for the diagnosis of FPLD. Additionally, an LFP < 29.6% appears to be a useful tool to aid in the diagnosis of these women., Conclusion: Combining anthropometric measurements to assess body fat distribution can lead to a more accurate diagnosis of FPLD. This study suggests new cutoff points for thigh skinfold and leg fat percentage in women with suspected FPLD in Brazil. Further studies are needed to confirm these findings., (© 2024. The Author(s).)

Background: Previous studies suggest intestinal dysbiosis is associated with metabolic diseases. However, the causal relationship between them is not fully elucidated. Gut microbiota evaluation of patients with congenital generalized lipodystrophy (CGL), a disease characterized by the absence of subcutaneous adipose tissue, insulin resistance, and diabetes since the first years of life, could provide insights into these relationships., Methods: A cross-sectional study was conducted with patients with CGL (n = 17) and healthy individuals (n = 17). The gut microbiome study was performed by sequencing the 16S rRNA gene through High-Throughput Sequencing (BiomeHub Biotechnologies, Brazil)., Results: The median age was 20.0 years old, and 64.7% were female. There was no difference between groups in pubertal stage, BMI, ethnicity, origin (rural or urban), delivery, breastfeeding, caloric intake, macronutrient, or fiber consumption. Lipodystrophic patients presented a lower alpha diversity (Richness index: 54.0 versus 67.5; p = 0.008). No differences were observed in the diversity parameters when analyzing the presence of diabetes, its complications, or the CGL subtype., Conclusion: In this study, we demonstrate for the first time a reduced gut microbiota diversity in individuals with CGL. Dysbiosis was present despite dietary treatment and was also observed in young patients. Our findings allow us to speculate that the loss of intestinal microbiota diversity may be due to metabolic abnormalities present since the first years of life in CGL. Longitudinal studies are needed to confirm these findings, clarifying the possible causal link between dysbiosis and insulin resistance in humans., (© 2022. The Author(s).)

Background: A new strain of human coronavirus (HCoV) spread rapidly around the world. Diabetes and obesity are associated with a worse prognosis in these patients. Congenital Generalized Lipodystrophy (CGL) patients generally have poorly controlled diabetes and require extremely high doses of insulin. There is no documentation in the literature of cases of COVID in CGL patients. Thus, we aimed to evaluate the prevalence of SARS-CoV-2 infection in CGL patients, and the association of their clinical and metabolic characteristics and outcomes., Methods: This is a cross-sectional study carried out between July and October 2020. Clinical data collected were respiratory or other flu-like symptoms, need of hospitalization in the last three months, CGL comorbidities, and medications in use. Cholesterol, triglycerides, glycohemoglobin A1c levels, anti-SARS-CoV-2 antibodies and nasopharyngeal swab for RT-qPCR were also obtained in all CGL patients. Mann-Whitney U test was used to analyze the characteristics of the participants, verifying the non-adherence of the data to the Gaussian distribution. In investigating the association between categorical variables, we used Pearson's chi-square test and Fisher's exact test. A significance level of 5% was adopted., Results: Twenty-two CGL patients were assessed. Eight subjects (36.4%) had reactive anti-SARS-CoV-2 antibodies. Only one of these, also presented detectable RT-qPCR. Five individuals (62.5%) were women, median age of 13.5 years (1 to 37). Symptoms like fever, malaise, nausea, diarrhea and chest pain were present, and all asymptomatic patients were children. All subjects had inadequate metabolic control, with no difference between groups. Among positive individuals there was no difference between those with AGPAT2 (75%) and BSCL2 gene mutations (25%) (p > 0.05). No patient needed hospitalization or died., Conclusions: We described a high prevalence of SARS-CoV-2 infection in CGL patients with a good outcome in all of them. These findings suggest that at least young CGL patients infected by SARS-COV-2 are not at higher risk of poor outcome, despite known severe metabolic comorbidities.

Background: Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by the near-total loss of subcutaneous adipose tissue soon after birth, resulting in ectopic fat deposition and severe metabolic disturbances. Most cases are caused by AGPAT2 or BSCL2 gene mutations. We aimed to report two unrelated CGL patients with a novel frameshift mutation in AGPAT2 (p.Leu124Serfs*26)., Methods: Clinical features and laboratory were obtained by medical interview and medical records review. DNA was extracted, amplified and sequenced. Mutation Taster was used to estimate the potential biological impact of the AGPAT2 mutations on the protein function., Results: Patient 1: a 30-year-old woman with lipodystrophy phenotype at birth and diagnosis of diabetes at age 13 presented with severe hypertriglyceridemia and pancreatitis at age 17, hypertension and albuminuria at age 18, proliferative diabetic retinopathy with visual loss at age 25, and an acute myocardial infarction due to multivessel coronary disease during a hospitalization for forefoot amputation at age 29. At this time, she required hemodialysis due to end-stage renal disease. Patient 2: a 12-year-old girl with lipodystrophy phenotype and hypertriglyceridemia detected in the first year of life and abnormalities in the global longitudinal strain, evaluated by speckle-tracking echocardiography last year. Molecular analysis identified a c.369&#95;372delGCTC (p.Leu124Serfs*26) AGPAT2 mutation in both unrelated patients, a compound heterozygous mutation in Patient 1, and homozygous mutation in Patient 2., Conclusion: We describe two unrelated patients with type 1 CGL due to Leu124Serfs*26, a novel AGPAT2 frameshift mutation, presenting as early cardiovascular disease. These findings suggest an association between Leu124Serfs*26 and a more aggressive phenotype., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: In type 1 diabetes mellitus (T1DM) management, enhancing health-related quality of life (HRQoL) is as important as good metabolic control and prevention of secondary complications. This study aims to evaluate possible regional differences in HRQoL, demographic features and clinical characteristics of patients with T1DM in Brazil, a country of continental proportions, as well as investigate which variables could influence the HRQoL of these individuals and contribute to these regional disparities., Methods: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group (BrazDiab1SG), by analyzing EuroQol scores from 3005 participants with T1DM, in 28 public clinics, among all geographical regions of Brazil. Data on demography, economic status, chronic complications, glycemic control and lipid profile were also collected., Results: We have found that the North-Northeast region presents a higher index in the assessment of the overall health status (EQ-VAS) compared to the Southeast (74.6 ± 30 and 70.4 ± 19, respectively; p < 0.05). In addition, North-Northeast presented a lower frequency of self-reported anxiety-depression compared to all regions of the country (North-Northeast: 1.53 ± 0.6; Southeast: 1.65 ± 0.7; South: 1.72 ± 0.7; Midwest: 1.67 ± 0.7; p < 0.05). These findings could not be entirely explained by the HbA1c levels or the other variables examined., Conclusions: Our study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of people with T1DM and contribute to these regional disparities.

Background: To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D)., Methods: This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups., Results: We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001)., Conclusions: Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits.