Eva Lau

Gut Microbiota: Association with NAFLD and Metabolic Disturbances.

Nonalcoholic fatty liver disease is the hepatic expression of metabolic syndrome, being frequently associated with obesity, insulin resistance, and dyslipidemia. Recent lines of evidence have demonstrated a role of gut microbiota in insulin resistance, obesity, and associated metabolic disturbances, raising the interest in its relationship with NAFLD pathogenesis. Therefore, intestinal microbiota has emerged as a potential factor involved in NAFLD, through different pathways, including its influence in energy storage, lipid and choline metabolism, ethanol production, immune balance, and inflammation. The main objective of this review is to address the pathogenic association of gut microbiota to NAFLD. This comprehension may allow the development of integrated strategies to modulate intestinal microbiota in order to treat NAFLD.

Beyond gut microbiota: understanding obesity and type 2 diabetes

Obesity and type 2 diabetes are metabolic diseases that have reached epidemic proportions worldwide. Although their etiology is complex, both result from interplay between behaviour, environment and genetic factors. Within ambient determinants, human overall gut bacteria have been identified as a crucial mediator of obesity and its consequences. Gut microbiota plays a crucial role in gastro-intestinal mucosa permeability and regulates the fermentation and absorption of dietary polyssacharides, which may explain its importance in the regulation of fat accumulation and the resultant development of obesity-related diseases. The main objective of this review is to address the pathogenic association between gut microbiota and obesity and to explore related innovative therapeutic targets. New insights into the role of the small bowel and gut microbiota in diabetes and obesity may make possible the development of integrated strategies to prevent and treat these metabolic disorders.

Subclinical hypothyroidism: to treat or not to treat, that is the question! A systematic review with meta-analysis on lipid profile

Previous studies suggested that subclinical hypothyroidism has a detrimental effect on cardiovascular risk factors, and that its effective treatment may have a beneficial impact on overall health. The main purpose of this review and meta-analysis was to assess whether subclinical hypothyroidism treatment is of clinical relevance, based on cardiovascular risk parameters correction. A systemic research of the literature using MEDLINE tool was performed to identify the relevant studies. Only placebo-controlled randomized control trials were included. A quantitative analysis was also performed. This systematic review and meta-analysis of randomized placebo-controlled trials assess the different impact of levothyroxine vs placebo treatment. A significant decrease in serum thyroid-stimulating hormone and total and low-density lipoprotein cholesterol was obtained with levothyroxine therapy (66, 9 and 14%, respectively) and, although modest, this could be significant in terms of reduction of the incidence of coronary artery disease. Other significant results of lipid parameters were not obtained. This systematic review provides a strong evidence-based data in favour of specific changes and beneficial effects of levothyroxine treatment.

Loss of mitochondrial SDHB expression: what is its role in diffuse thyroid lipomatosis?

Diffuse lipomatosis of the thyroid gland is a very rare disease, characterized by extensive infiltration of thyroid parenchyma by mature adipose tissue, usually not accompanied by amyloid fibrils deposition. The pathophysiology of adipose tissue infiltration in the thyroid gland remains unknown. We report a clinical case of a diffuse thyroid lipomatosis, whose immunohistochemical study of succinate dehydrogenase - subunit B (SDHB) revealed loss of expression of this protein in the follicular or adipose cells. We detected the presence of a recently described SDHB gene large deletion. Loss of mitochondrial SDHB expression may have a key role in understanding the pathophysiology of thyrolipomatosis, by regulating status of lipid metabolism.

Permanent neonatal diabetes by a new mutation in KCNJ11: unsuccessful switch to sulfonylurea

Permanent neonatal diabetes (PNDM) can result from activating heterozygous mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channels (KATP). Sulfonylureas promote KATP closure and stimulate insulin secretion, being an alternative therapy in PNDM, instead of insulin. Male, 20 years old, diagnosed with diabetes at 3 months of age. The genetic study identified a novel heterozygous mutation in exon 1 of the KCNJ11 gene - KCNJ11:c1001G>7 (p.Gly334Val) - and confirmed the diagnosis of PNDM. Therefore it was attempted to switch from insulin therapy to sulfonylurea. During glibenclamide institution C-peptide levels increased, however the suboptimal glycemic control lead us to restart an intensive insulin scheme. This new variant of KCNJ11 mutation had a phenotypic lack of response to sulfonylurea therapy. Age, prior poor metabolic control and functional change of KATP channel induced by this specific mutation may explain the observed unsuccessful switch to sulfonylurea. Interestingly, C-peptide levels raise during glibenclamide administration support some degree of improvement in insulin secretory capacity induced by the treatment. Understanding the response to sulfonylurea is crucial as successful treatment may be life-changing in these patients.

HIV-Infected Patients With and Without Lipodystrophy Under Combined Antiretroviral Therapy: Evaluation of Body Composition

In HIV-infected patients, combined antiretroviral therapy (cART) is associated to adipose tissue redistribution known as lipodystrophy and associated cardiometabolic risk. This study aimed to evaluate the evolution of body composition in HIV-infected patients, with and without lipodystrophy, over 2 yr. We evaluated anthropometric parameters and body composition by whole-body dual-energy X-ray absorptiometry in 144 HIV-infected patients on cART. We defined lipodystrophy by fat mass ratio. Lipodystrophy was present in 45.77% of the patients. These patients presented higher HIV infection duration, cART duration, and CD4+ cell count, with no differences regarding gender, age, body mass index, and viral load. Patients with lipodystrophy showed an increase in total fat mass (9.9%) and upper-limbs fat mass (17.6%), with a decrease in total, trunk, and lower-limbs fat-free mass (2.2%; 2.2%, and 3.9%, respectively), over 2 yr. In patients without lipodystrophy, the trunk fat-free mass decreased 1.9% over time, and no changes were observed in the other studied parameters. In patients with lipodystrophy, there was predominantly a central fat mass gain, with no changes in lower limbs, suggesting that peripheral adipocytes lose their regenerative capacity.

Familial partial lipodystrophy type 3: a new mutation on the PPARG gene.

Introduction: Familial partial lipodystrophy is an autosomal dominant genetic disorder, characterized by lipoatrophy of extremities and gluteal region and lipohypertrophy of face, neck and/or trunk. It is associated with insulin resistance, hypertriglyceridemia and increased risk of recurrent episodes of pancreatitis. The PPARG mutations forms, called familial partial lipodystrophies type 3, are very rare, accounting for approximately only 30 patients. Case report: We report the case of a 60 years old caucasian woman that had started to develop gradual fat loss of extremities and gluteal region and facial and abdominal fat increase at 30 years old. Subsequently, type V dyslipidemia and diabetes were diagnosed and she had an acute pancreatitis. Physical examination confirmed clinical lipodystrophy. Genetic study showed a heterozygous mutation in the PPARG (p.Gly161Val; c.482G> T), not previously described. Conclusion: Clinical appearance and past medical history, in conjunction with genetic study have allowed the identification of a novel gene mutation in PPARG , enabling the diagnosis of familial partial lipodystrophy type 3. This case highlights the importance of an early recognition of a lipodystrophy syndrome, in order to prevent metabolic complications, recurrent pancreatitis, and the onset of cardiovascular disease.

Female to male gender identity disorder in a patient with non-classical congenital adrenal hyperplasia

Case Report: A 22-year-old patient(46, XX), was sent from Psychiatry-Sexology to Endocrinology consultation for GID to start hormonal treatment. Self-awareness as a male began at 12-year-old. Menarche at the age of 13 years. At 14-year-old, it was noticed overgrowth of terminal hair with male pattern. Since 16-year-old with oligomenorrhea. No history of previous hormonal therapy. On physical examination, signs of virilization hirsutism (Ferriman Gallwey scale score: 32), clitoromegaly and deep voice and android obesity (W=106 Kg, H=1.80 m, BMI=32.7 Kg/m). Laboratory assays showed increased 17 OH-progesterone (8.3 ng/ml (0.42–3.5)), androstenedione (9.59 ng/ml (0.6–3.1)) and ACTH (157.1 ng/l ( 10 ng/ml (30.5) 60 min after tetracosactide), excluding cortisol deficiency. Molecular study of 21-hydroxylase genes enabled the detection of a mutation c.290-13 (A / C> G) in heterozygosity, and P. Val281Leu in homozygosity in CYP21A2 gene, confirming the diagnosis. The patient began hormonal therapy with testosterone enanthate (250 mg IM every 4 weeks) to optimize the phenotype and achieve male physiological levels of testosterone.

CO044. UM EM CADA 5 DOENTES COM INFECÇÃO VIH TÊM HIPOGONADISMO

e o tecido adiposo visceral (VAT) abdominal, que individualmente podem ter contributos diferentes para as alteracoes metabolicas. Os doentes com infeccao VIH sob terapeutica anti-retrovirica (TAR) podem ter alteracoes da composicao corporal, que se podem reflectir em diferente distribuicao do TA. Objetivo: Avaliar a SAT, VAT e razao VAT/SAT avaliada por TC a nivel abdominal: 1) em doentes infectados pelo VIH-1 sob TAR vs controlos nao infectados; 2) em doentes com e sem lipodistrofia definida pela clinica vs controlos; 3) em doentes com lipodistro-fia definida pela “razao massa gorda tronco/membros” (RMGTM) definida por DEXA vs controlos. Metodos: Avaliamos em 173 controlos e 211 doentes com infeccao VIH-1 sob TAR, parâmetros antropometricos e a massa gorda a nivel abdominal determinada por TC SAT, VAT e VAT/SAT, apos ajuste para a idade e IMC. Resultados: Independentemente do genero, a massa gorda total (MGT) e SAT era maior nos controlos do que nas doentes VIH e a razao VAT/SAT era maior nas doentes. Quando considerada a lipodistrofia clinica, nas mulheres, a SAT era maior nos controlos e naquelas sem lipodistrofia, sendo a razao VAT/SAT maior nas com infeccao (com ou sem LC). Nos homens, a MGT e SAT era maior nos controlos e naqueles sem LC; a razao VAT/SAT era maior nos que tinham infeccao (com ou sem LC). Se lipodistrofia definida por RMGTM, observou-se que nas mulheres, a SAT era maior nos controlos e nas sem lipodistrofia e a razao VAT/SAT era maior nas com infeccao (com ou sem lipodistrof ia). Nos homens, a MGT e SAT era maior nos controlos e naqueles sem lipodistrofia; a razao VAT/SAT era maior nos com infeccao (quer com ou sem lipodistrofia). Em ambos os generos observou-se maior VAT nos com lipodistrofia. Conclusao: Observou-se maior VAT/SAT nos doentes infectados, independentemente do genero e da definicao de lipodistrofia utilizada.