Clinical and genetic characterization and long-term evaluation of individuals with maturity-onset diabetes of the young (MODY): The journey towards appropriate treatment.

AIMS: To describe the clinical and genetic characteristics and long-term follow-up of a cohort with maturity-onset diabetes of the young (MODY), and to evaluate how molecular diagnosis impacted on treatment. METHODS: A large observational, retrospective, cohort study included individuals referred to the University of São Paulo's Monogenic Diabetes Unit between 2011 and 2020. Comprehensive clinical and genetic evaluations were performed. RESULTS: Overall, 228 individuals (190 GCK-MODY and 38 HNF1A-MODY) were enrolled. Sixty-two different GCK gene mutations (5 novel) and 17 HNF1A gene mutations (2 novel) were found. Data were available on treatment status for 76 index individuals with GCK-MODY. Before molecular diagnosis, nutritional intervention alone was used in 41 cases (53.9%). After molecular diagnosis, this number increased to 72 (94.8%). Glycated haemoglobin (HbA1c) remained stable over the 6-year follow-up period: 6.5% (47 mmol/mol) at the first and 6.3% (45 mmol/mol) at the final visit (p = 0.056). Prior to molecular diagnosis, 7/21 (33.3%) HNF1A-MODY individuals were using sulfonylurea compared to 17/21 (81%) after testing. After a median of 5 years on sulfonylureas, HbA1c values improved from 7.5% (58 mmol/mol) to 6.5% (48 mmol/mol) (p = 0.006). CONCLUSIONS: Molecular diagnosis resulted in appropriate adjustment of treatment in approximately 80% of participants with GCK-MODY or HNF1A-MODY.

A relação da circunferência abdominal com outros componentes da síndrome metabólica em pacientes atendidos na feira de saúde da FMABC em 2008 / Relationship of abdominal circumference with other metabolic syndrome components in patients seen during the FMABC health fair in 2008

JUSTIFICATIVA E OBJETIVOS: Síndrome metabólica,atualmente considerada epidemia mundial, caracteriza-se pela associação de dislipidemia, diabetes mellitus/intolerância à glicose, hipertensão arterial e obesidade. Interligando estas alterações metabólicas está a resistência à insulina. Sua presença leva ao aumento do risco de doenças cardiovasculares. O objetivo deste estudo foi demonstrara existência de uma síndrome, ao invés de doenças isoladas, relacionando circunferência abdominal, glicemia e pressão arterial (PA). MÉTODO: Foram atendidos 473 pacientes na Feira de Saúde em 2008 da FMABC pela Liga de Controle do Diabetes. Variáveis mensuradas: glicemia, peso, altura, índicede massa corpórea (IMC), circunferência abdominal (CA) e pressão arterial. Dados coletados: hábitos, uso de medicamentos, antecedentes pessoais e familiares. Foram excluídos pacientes < 18 ou > 79 anos, em uso de anti-hipertensivos e antidiabéticos. RESULTADOS: Foram analisados 148 pacientes, sendo 92 mulheres, idade média de 40,37 ± 14,1 anos. A média de glicemia foi 100,3 ± 18,9 mg/dL, de CA foi 88,1 ± 13,4 cm e a de IMC 26,8 ± 5,4 kg/m2. Dos homens que estavam de jejum, 9% tinham CA aumentada (> 104 cm), sendo 50% intolerante à glicose (glicemia > 100 mg/dL), com p = 0,03. Já no sexo feminino 48,9% não estava de jejum, sendo 55% destas com CA > 88 cm. Entre os pacientes masculinos com CA alterada, 62,5% tinham PA > 130 x 85 mmHg, com p = 0,04. Já no sexo feminino, 23,9% com CA > 88 cm apresentaram níveis de PA elevados. Não houve significância estatística entre CA, hiperglicemiae PA entre as mulheres. CONCLUSÃO: O presente estudo mostrou que a circunferência abdominal aumentada se relaciona com intolerância à glicose e hipertensão, principalmente entre os homens. Isso corrobora com a literatura que busca demonstrar a existência de uma síndrome como fator de risco para fenômenos ateroscleróticos.

[Metformin and AMPK: an old drug and a new enzyme in the context of metabolic syndrome]. / Metformina e AMPK: um antigo fármaco e uma nova enzima no contexto da síndrome metabólica.

Metformin is one of the most commonly prescribed oral antidiabetic agents worldwide. However, its mechanism of action remains unknown. The Diabetes Prevention Program Research Group studies have shown that metformin administration and lifestyle-intervention (diet and exercise) reduce the incidence of Diabetes Mellitus type 2 (DM2). A possible biochemical connection between both therapies may be the AMP-activated protein kinase (AMPK). This enzyme was originally described as a sensor of cellular energy status, being activated in exercise. On the other hand, several experimental evidences indicate that AMPK may be an important target of metformin action. This paper discusses various ways for AMPK regulation, suggesting a possible mechanism for its activation by metformin that involves the production of reactive nitrogen species. AMPK activation determines a wide variety of physiological effects, including enhanced glucose uptake by skeletal muscle and enhanced lipid catabolism. Thus, it may be a key player not only in the prevention and treatment of DM2, but also in the development of new treatments for obesity and the metabolic syndrome. The finding of AMPK activation by metformin draws attention to this enzyme as an important pharmacological target.