ABSTRACT Objectives To evaluate the accuracy of routinely available parameters in screening for GCK maturity-onset diabetes of the young (MODY), leveraging data from two large cohorts – one of patients with GCK-MODY and the other of patients with type 1 diabetes (T1D). Materials and methods The study included 2,687 patients with T1D, 202 patients with clinical features of MODY but without associated genetic variants (NoVar), and 100 patients with GCK-MODY (GCK). Area under the receiver-operating characteristic curve (ROC-AUC) analyses were used to assess the performance of each parameter – both alone and incorporated into regression models – in discriminating between groups. Results The best parameter discriminating between GCK-MODY and T1D was a multivariable model comprising glycated hemoglobin (HbA1c), fasting plasma glucose, age at diagnosis, hypertension, microvascular complications, previous diabetic ketoacidosis, and family history of diabetes. This model had a ROC-AUC value of 0.980 (95% confidence interval [CI] 0.974-0.985) and positive (PPV) and negative (NPV) predictive values of 43.74% and 100%, respectively. The best model discriminating between GCK and NoVar included HbA1c, age at diagnosis, hypertension, and triglycerides and had a ROC-AUC value of 0.850 (95% CI 0.783-0.916), PPV of 88.36%, and NPV of 97.7%; however, this model was not significantly different from the others. A novel GCK variant was also described in one individual with MODY (7-44192948-T-C, p.Ser54Gly), which showed evidence of pathogenicity on in silico prediction tools. Conclusions This study identified a highly accurate (98%) composite model for differentiating GCK-MODY and T1D. This model may help clinicians select patients for genetic evaluation of monogenic diabetes, enabling them to implement correct treatment without overusing limited resources. maturityonset maturity onset MODY, , (MODY) GCKMODY TD . T D (T1D) 2687 2 687 2,68 20 NoVar, (NoVar) 10 GCK. (GCK) receiveroperating receiver operating ROCAUC ROC AUC (ROC-AUC groups HbA1c HbAc HbA c (HbA1c) glucose diagnosis hypertension complications ketoacidosis 0980 0 980 0.98 95% 95 (95 [CI 0.9740.985 09740985 0.974 0.985 974 985 0.974-0.985 (PPV (NPV 4374 43 74 43.74 100% respectively 0850 850 0.85 0.7830.916, 07830916 0.783 0.916 783 916 0.783-0.916) 8836 88 36 88.36% 97.7% 977 97 7 however others 744192948TC, 744192948TC TC 44192948 C, C (7-44192948-T-C p.Ser54Gly, pSer54Gly pSerGly p.Ser54Gly p Ser54Gly Ser Gly p.Ser54Gly) tools 98% 98 (98% resources (MODY (T1D 268 68 2,6 (NoVar (GCK (HbA1c 098 0.9 9 (9 9740 0.9740.98 0974098 0974 0.97 0985 0.974-0.98 437 4 43.7 085 85 0.8 7830 0.7830.916 0783091 0783 0.78 0916 0.91 78 91 0.783-0.916 883 8 3 88.36 97.7 4419294 pSer SerGly (98 26 6 2, 09 0. ( 0.9740.9 097409 097 0.974-0.9 43. 08 0.7830.91 078309 078 0.7 091 0.783-0.91 88.3 97. 441929 0.9740. 09740 0.974-0. 0.7830.9 07830 07 0.783-0.9 88. 44192 0.9740 0.974-0 0.7830. 0.783-0. 4419 0.974- 0.7830 0.783-0 441 0.783- 44

Diabetes mitocondrial ou diabetes e surdez de herança maternal (MIDD, acrônimo de maternally inherited diabetes and deafness) é freqüentemente associado à mutação mitocondrial A3243G. Esse subtipo de diabetes é caracterizado por transmissão materna, disacusia neuro-sensorial bilateral e idade precoce de aparecimento. Além do diabetes e da surdez, principais características diagnósticas, outros sintomas em diferentes órgãos podem também associar-se à mutação A3243G. Os órgãos que são metabolicamente mais ativos, tais como músculos, miocárdio, retina, cóclea, rim e cérebro, são freqüentemente afetados. Sintomas do trato gastrintestinal também são comuns em pacientes com doença mitocondrial, sendo diarréia e obstipação as manifestações mais freqüentes. Entretanto, há poucos relatos de pseudo-obstrução intestinal em portadores de diabetes mitocondrial. Este relato descreve o caso de uma paciente com diabetes mitocondrial que apresentou pseudo-obstrução intestinal e que com a introdução de coenzima Q10, como terapia adjunta, teve resolução o quadro.

Maternally inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. This subtype of diabetes is characterized by maternal transmission, young age at onset and bilateral hearing impairment. Besides diabetes and deafness, the main diagnostic features, a wide range of multisystemic symptoms may be associated with the A3243G mutation. Organs that are most metabolically active, such as muscles, myocardium, retina, cochlea, kidney and brain are frequently affected. Gastrointestinal tract symptoms are also common in patients with mitochondrial disease and constipation and diarrhea are the most frequent manifestations. However, there are few prior reports of intestinal pseudo obstruction in MIDD patients. Here we report the case of a patient with MIDD associated with the mtDNA A3243G mutation who developed chronic intestinal pseudo obstruction, and the introduction of Coenzyme Q10 as adjunctive therapy led to a solution of the pseudo obstruction.

As lipodistrofias são um grupo heterogêneo de doenças caracterizadas por perda de tecido adiposo e complicações metabólicas. As formas hereditárias mais importantes de lipodistrofias são: lipodistrofia congênita generalizada e lipodistrofia parcial familiar (LDPF). LDPF resulta de mutações no gene LMNA que codificam as lâminas tipo A. Além da LDPF, mutações no gene LMNA são responsáveis por outras doenças hereditárias, denominadas laminopatias. Descrevemos o caso de uma paciente de 15 anos de idade encaminhada por diabetes melito e hipertrigliceridemia grave. Ao exame físico, apresentava perda generalizada de gordura subcutânea que foi confirmada por DEXA (gordura corporal total 8,6%). Como a paciente apresentava perda de gordura de início na puberdade e resistência insulínica, foi realizada análise molecular do gene LMNA. Identificamos uma substituição em heterozigose no éxon 1 (c.29C>T), resultando na mutação p.T10I. Em sumário, um caso de fenótipo atípico de lipodistrofia generalizada devido à mutação de novo p.T10I no gene LMNA é descrito.

Lipodystrophies are a group of heterogeneous disorders characterized by the loss of adipose tissue and metabolic complications. The main familial forms of lipodystrophy are Congenital Generalized Lipodystrophy and Familial Partial Lipodystrophy (FPLD). FPLD may result from mutations in the LMNA gene. Besides FPLD, mutations in LMNA have been shown to be responsible for other inherited diseases called laminopathies. Here we describe the case of a 15-year-old girl who was referred to our service due to diabetes mellitus and severe hypertriglyceridemia. Physical examination revealed generalized loss of subcutaneous fat, confirmed by DEXA (total body fat 8.6%). As the patient presented with pubertal-onset of generalized lipodystrophy and insulin resistance, molecular analysis of the LMNA gene was performed. We identified a heterozygous substitution in exon 1 (c.29C>T) predicting a p.T10I mutation. In summary, we describe an atypical phenotype of lipodistrophy associated with a de novo appearance of the p.T10I mutation in LMNA gene.

OBJETIVO: análise crítica dos estudos sobre a epidemiologia, fisiopatologia, diagnóstico e tratamento do DM2 no jovem. MÉTODOS: revisão da literatura nos últimos 10 anos, através de pesquisa no banco de dados Medline, utilizando os termos "diabetes do tipo 2 no jovem". RESULTADOS: a fisiopatologia do DM2 no jovem é semelhante à do adulto, e compreende tanto a resistência à ação da insulina como uma alteração na função da célula beta-pancreática. O antecedente familiar para DM2, a presença de obesidade, a acanthosis nigricans, o peptídeo C de jejum superior a 0,6 ng/ml, a ausência de auto-anticorpos antiilhotas pancreáticas, em combinações variáveis, são pontos importantes para o diagnóstico desse tipo de DM. Cinco a 25% dos jovens com esse tipo de DM podem apresentar cetoacidose no diagnóstico. Nesses pacientes, o tratamento inicial com insulina é possível de ser descontinuado durante a evolução. A aderência à dieta e ao exercício físico são os elementos mais importantes do tratamento destes adolescentes. CONCLUSÃO: como a obesidade nos jovens tem aumentado, tanto em países industrializados como nos países em industrialização, o DM2 no jovem pode ser considerado um problema emergente também na nossa população.

OBJECTIVE: the objective of this manuscript was to perform a critical review of epidemiology, pathophysiology, diagnosis e treatment of T2DM in youth. SOURCES OF DATA: this review is based on the relevant literature published. The sources available for the authors were integrated with sources identified through Medline database. The key words used for searching were "Type 2 Diabetes in the Youth" in the last ten years. SUMMARY OF THE FINDINGS: the pathophysiology (altered beta-cell function and insulin resistance) of T2DM in youth is similar to adult's pathophysiology. Familiar Type 2 diabetes history, presence of obesity, acanthosis nigricans, high fasting plasma C-peptide levels and absence of islet-cell auto-antibodies are important clues to diagnostic the T2DM in youth. Five to 25% of these patients can present ketosis at diagnosis. Insulin therapy can be discontinued during the evolution. Compliance to diet and an exercise program essential aspects of the treatment of adolescents. CONCLUSION: as obesity in the young is currently increasing in several developed or developing countries, T2DM in the youth can be consider an emergent problem also in our population.