Risk factors associated with diabetes after liver transplant

ABSTRACT Objective: Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after liver transplant that negatively affects a recipient's survival and graft function. This study aims to identify risk factors associated with diabetes after liver transplant. Materials and methods: This is a cross-sectional study conducted from September to November 2019. Data collection was performed by chart review, and patients were divided into 3 groups: patients without diabetes mellitus (DM), patients with pre-transplant diabetes mellitus, and patients with PTDM. Results: Two hundred and forty-seven patients' medical charts were screened, and 207 patients were included: 107 without DM, 42 with pre-transplant DM, and 58 with PTDM. The leading cause for liver transplant was hepatitis C, followed by hepatocellular carcinoma secondary to alcohol. There was a higher exposure to tacrolimus in patients without DM ( P = 0.02) and to ciclosporin in patients with pre-transplant DM, compared to others ( P = 0.005). Microscopic interface inflammatory activity was more severe in patients without DM as well as those with PTDM ( P = 0.032). There was a higher prevalence of steatosis in recipients with pre-transplant DM than there was in others ( P < 0.001). Multivariate logistic regression identified the following independent risk factors for DM: cirrhosis due to alcohol, hepatitis C, and triglycerides. For PTDM, these independent risk factors were cirrhosis due to alcohol, hepatitis C, and prednisone exposure. Conclusion: Alcoholic cirrhosis is a risk factor for PTDM in liver recipients. Liver transplant recipients with a pre-transplant history of cirrhosis due to alcohol, hepatitis C, and prednisone exposure deserve more caution during PTDM screening.

Heterotaxy syndrome with agenesis of dorsal pancreas and diabetes mellitus: case report and review of the literature

SUMMARY Heterotaxy syndrome (HS) is a rare congenital condition with multifactorial heritance, characterized by an abnormal arrangement of thoraco-abdominal organs and vessels. Patients present with multiple cardiac, gastrointestinal, hepatosplenic, pancreatic, renal, neurological and skeletal disorders without any pathognomonic alteration. Despite the described increased risk of diabetes mellitus (DM) in patients with altered pancreatic anatomy, just one case was reported in Korea regarding the association of HS and DM in a 13-year-old girl. Our report refers to a 40-year-old female Brazilian patient with a history of DM and HS with polysplenia and agenesis of dorsal pancreas without cardiac abnormalities. She presented a worsening glycemic control associated with weight gain and signs of insulin resistance. After a proper clinical management of insulin and oral medications, our patient developed an improvement in glycemic control. Although it is a rare disease, HS with polysplenia and pancreatic disorders can be associated with an increased risk of DM. This case highlights the importance of investigating DM in patients with HS, especially those with pancreatic anatomical disorders, for proper clinical management of this rare condition.

Síndrome do eutireoidiano doente em pacientes com diabetes mellitus tipo 2: correlação com marcadores inflamatórios, controle glicêmico e relação com doença cardiovascular / Euthyroid sick syndrome in patients with type 2 diabetes mellitus: correlation between inflammatory markers, glycemic control and relationship with cardiovascular disease

A síndrome do eutireoidiano doente (SED) é uma entidade caracterizada pela queda das concentrações sanguíneas de triiodotironina nas formas total e livre e aumento da forma reversa. Ocorre principalmente em pacientes portadores de doenças graves e agudas, particularmente dentre aqueles internados em unidade de terapia intensiva. Há descrição desta síndrome em portadores de Diabetes Mellitus, particularmente sob controle glicêmico inadequado. Objetivos: Avaliar as alterações dos hormônios tireoidianos em portadores de DM sob cuidado ambulatorial e a correlação entre concentrações de hormônios tireoidianos e controle glicêmico, presença de complicações crônicas (neuropatia, nefropatia, retinopatia) e marcadores de inflamação sistêmica subclínica, bem como sua relação com presença de eventos cardiovasculares. Metodologia: Estudo transversal avaliando 52 pacientes com diabetes tipo 2 e 52 indivíduos sem diabetes, entre 40 e 75 anos de idade, pareados por sexo, idade e índice de massa corporal. Avaliaram-se dados clínicos e antropométricos, concentrações séricas de hormônios tireoidianos e proteína C reativa, bem como exames laboratoriais que refletem o perfil lipídico e controle glicêmico. Resultados: Cerca de 73% dos pacientes com diabetes e 40% dos indivíduos sem DM apresentaram concentrações séricas diminuídas de T3 total; 25% dos pacientes e apenas 2% dos indivíduos sem DM apresentaram concentrações diminuídas de T3 livre. As concentrações séricas de T3 total (p<0,001), T3 livre (p<0,001) e T4 total (p=0,006) estavam diminuídas em comparação aos de indivíduos sem diabetes. As concentrações de T3 reverso não apresentaram diferença entre os dois grupos. Pacientes com diabetes apresentaram T4 livre mais elevado (p=0,033).

The non-thyroidal illness is an entity characterized by reduced serum levels of total and free triiodothyronine and a rise in its reverse form. It occurs mainly in critically ill patients. There are descriptions of this syndrome in patients with Diabetes Mellitus, especially those under inadequate glycemic control. Objectives: Evaluate the abnormalities in thyroid hormone levels in individuals with diabetes under standard outpatient care and the correlation of thyroid hormone levels with glycemic control, presence of chronic complications (neuropathy, nephropathy and retinopathy) and subclinical systemic inflammation, as well as its relation with the presence of previous cardiovascular events. Methodology: Cross sectional study involving 52 patients with type 2 diabetes and 52 individuals without the diabetes, between 40 and 75 years of age paired by age, gender and body mass index. We evaluated clinical and anthropometric data, serum levels of thyroid hormones and Creactive protein, as well as laboratory parameters that reflect the lipid profile and glycemic control. Results: Approximately 73% of the patients with diabetes and 40% of individuals without diabetes presented reduced serum levels of total T3. Nearly 25% of the patients and only 2% of the individuals without diabetes presented reduced levels of free T3. The levels of total T3 (p<0.001), free T3 (p<0.001) and total T4 (p=0.006) were lower in patients with diabetes compared with those without diabetes. The levels of reverse T3 did not present any difference between both groups. Patients with diabetes presented higher levels of free T4 (p=0.033). The levels of reverse T3 were significantly different only when comparing individuals with previous cardiovascular events with those without this characteristic (p=0.002 for patients with diabetes and p=0.037 for individuals without diabetes). The prevalence of cardiovascular disease was 25%.

Long-term follow-up of an 8-year-old boy with insulinoma as the first manifestation of a familial form of multiple endocrine neoplasia type 1 / Seguimento de longo prazo em um menino de 8 anos de idade com insulinoma como primeira manifestação de neoplasia endócrina múltipla tipo 1

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary cancer syndrome characterized mostly by parathyroid, enteropancreatic, and anterior pituitary tumors. We present a case of an 8-year-old boy referred because of hypoglycemic attacks. His diagnosis was pancreatic insulinoma. Paternal grandmother died due to repeated gastroduodenal ulcerations and a paternal aunt presented similar manifestations. At a first evaluation, the father presented only gastric ulceration but subsequently developed hyperparathyroidism and lung carcinoid tumor. During almost 15 years of follow-up, three brothers and the index case presented hyperparathyroidism and hyperprolactinemia. Molecular study showed a G to A substitution in intron 4, at nine nucleotides upstream of the splicing acceptor site, causing a splicing mutation. All affected members of the family have the same mutation. Paternal grandmother and aunt were not studied and the mother does not carry any mutation. MEN1 is a rare condition that requires permanent medical assistance. Early clinical and genetic identification of affected individuals is essential for their own surveillance and also for genetic counseling.

A neoplasia endócrina múltipla tipo 1 (NEM1) é uma doença hereditária autossômica dominante, caracterizada principalmente por tumores de paratireoide, enteropancreáticos e adeno-hipofisários. Apresentamos o caso de um menino com 8 anos encaminhado por crises de hipoglicemia. Seu diagnóstico foi insulinoma pancreático. Sua avó paterna faleceu por úlceras gastroduodenais de repetição e a tia paterna tinha as mesmas manifestações. Na primeira avaliação, o pai apresentou apenas úlcera gástrica, porém com a evolução desenvolveu hiperparatireoidismo e tumor carcinoide pulmonar. Durante cerca de 15 anos de seguimento, os três irmãos e o caso índice desenvolveram hiperparatireoidismo e hiperprolactinemia. O estudo molecular mostrou a substituição G por A no intron 4, a nove nucleotídeos do sítio aceptor de splicing, criando um novo sítio de splicing. Todos os membros da família afetados e estudados tinham a mesma mutação. A NEM1 é uma condição rara que requer assistência médica permanente. As identificações clínicas e genéticas precoces são essenciais para o tratamento e aconselhamento genético.