Importance of clinical variables in the diagnosis of MODY2 and MODY3

La diabetes tipo MODY (del inglés maturity onset diabetes of the young) constituye un grupo de patologías bien definidas y caracterizadas por su aparición antes de los 25 años, herencia autosómica dominante y por el hecho de que no precisan un tratamiento con insulina (al menos, inicialmente) para evitar la formación de cuerpos cetónicos. A pesar de la importancia de una clasificación precisa del paciente diabético, no siempre resulta sencillo clasificar el diagnóstico de un paciente joven con diabetes, y los estudios genéticos, a menudo, se usan de forma inadecuada. Métodos Se describen las características clínicas de pacientes cuyo estudio para MODY2 y MODY3 resultó negativo, y se comparan con las características de pacientes con resultado de estudio positivo. Resultados Todos los pacientes con MODY3 habían sido diagnosticados antes de los 25 años de edad y requerían algún tratamiento farmacológico para controlar la glucemia. Los pacientes con MODY2 fueron diagnosticados a partir de la primera analítica realizada, bien de forma accidental o dentro de un contexto de cribado de diabetes gestacional. La descripción clínica de los 19 pacientes cuyo estudio para MODY2 y MODY3 resultó negativo, mostró que sólo dos pacientes presentaban un cuadro clínico compatible con MODY3 y solo un paciente con MODY2.ConclusionesLas características clínicas pueden ser utilizadas para excluir el diagnóstico de MODY2 y MODY3, y ello puede reducir la necesidad de estudios genéticos (AU)

MODY (maturity onset diabetes of the young) is a group of well-defined diseases clinically characterised by onset before age 25 years that does not require insulin treatment (at least initially)to prevent the formation of ketone bodies and autosomal dominant inheritance. Despite the importance of accurate classification, it is not always simple to catalogue the diagnosis of a young patient with diabetes, and genetic studies are often improperly used. Methods: We describe the clinical features of patients negative for MODY2 and MODY3 and compared them to patients positive for these subtypes. Results: All patients with MODY3 had been diagnosed before age 25 years and required drug therapy for blood glucose control. MODY2 patients were diagnosed at the first laboratory workup either incidentally or as part of gestational diabetes screening. The clinical description of the19 patients negative for MODY2 and MODY3 showed that only two patients presented a clinical picture consistent with MODY3 and one patient with MODY2.Conclusions: Clinical features can be used for early exclusion of a MODY2 or MODY3 diagnosis and may reduce the need for genetic testing (AU)

Importance of clinical variables in the diagnosis of MODY2 and MODY3.

AIMS: MODY (maturity onset diabetes of the young) is a group of well-defined diseases clinically characterised by onset before age 25 years that does not require insulin treatment (at least initially) to prevent the formation of ketone bodies and autosomal dominant inheritance. Despite the importance of accurate classification, it is not always simple to catalogue the diagnosis of a young patient with diabetes, and genetic studies are often improperly used. METHODS: We describe the clinical features of patients negative for MODY2 and MODY3 and compared them to patients positive for these subtypes. RESULTS: All patients with MODY3 had been diagnosed before age 25 years and required drug therapy for blood glucose control. MODY2 patients were diagnosed at the first laboratory workup either incidentally or as part of gestational diabetes screening. The clinical description of the 19 patients negative for MODY2 and MODY3 showed that only two patients presented a clinical picture consistent with MODY3 and one patient with MODY2. CONCLUSIONS: Clinical features can be used for early exclusion of a MODY2 or MODY3 diagnosis and may reduce the need for genetic testing.

Clinical differences between patients with MODY-3, MODY-2 and type 2 diabetes mellitus with I27L polymorphism in the HNF1alpha gene.

OBJECTIVE: The aim of our study was to describe and evaluate the clinical and metabolic characteristics of patients with MODY-3, MODY-2 or type 2 diabetes who presented I27L polymorphism in the HNF1alpha gene. METHODS: The study included 31 previously diagnosed subjects under follow-up for MODY-3 (10 subjects from 5 families), MODY-2 (15 subjects from 9 families), or type 2 diabetes (6 subjects) with I27L polymorphism in the HNF1alpha gene. The demographic, clinical, metabolic, and genetic characteristics of all patients were analyzed. RESULTS: No differences were observed in distribution according to sex, age of onset, or form of diagnosis. All patients with MODY-2 or MODY-3 had a family history of diabetes. In contrast, 33.3% of patients with type 2 diabetes mellitus and I27L polymorphism in the HNF1alpha gene had no family history of diabetes (p < 0.05). No differences were observed in body mass index, prevalence of hypertension, or microvascular or macrovascular complications. Drug therapy was required by 100% of MODY-3 patients, but not required by 100% of MODY-2 patients or 16.7% of patients with type 2 diabetes mellitus and I27L polymorphism in the HNF1alpha gene (p < 0.05). CONCLUSIONS: Occasional difficulties may be encountered when classifying patients with MODY-2, MODY-3 or type 2 diabetes of atypical characteristics, in this case patients who present I27L polymorphism in the HNF1alpha gene.

Clinical differences between patients with MODY-3, MODY-2 and type 2 diabetes mellitus with I27L polymorphism in the HNF1alfa gene

Objective: The aim of our study was to describe and evaluate the clinical and metabolic characteristics of patients with MODY-3, MODY-2 or type 2 diabetes who presented I27L polymorphism in the HNF1α gene. Methods: The study included 31 previously diagnosed subjects under follow-up for MODY-3 (10 subjects from 5 families), MODY-2 (15 subjects from 9 families), or type 2 diabetes (6 subjects) with I27L polymorphism in the HNF1α gene. The demographic, clinical, metabolic, and genetic characteristics of all patients were analyzed. Results: No differences were observed in distribution according to sex, age of onset, or form of diagnosis. All patients with MODY-2 or MODY-3 had a family history of diabetes. In contrast, 33.3% of patients with type 2 diabetes mellitus and I27L polymorphism in the HNF1α gene had no family history of diabetes (p < 0.05). No differences were observed in body mass index, prevalence of hypertension, or microvascular or macrovascular complications. Drug therapy was required by 100% of MODY-3 patients, but not required by 100% of MODY-2 patients or 16.7% of patients with type 2 diabetes mellitus and I27L polymorphism in the HNF1α gene (p < 0.05). Conclusions: Occasional difficulties may be encountered when classifying patients with MODY-2, MODY-3 or type 2 diabetes of atypical characteristics, in this case patients who present I27L polymorphism in the HNF1α gene

Objetivos: El objetivo de este estudio es describir y evaluar las características clínicas y metabólicas de pacientes diabéticos MODY 3, MODY 2 y con diabetes tipo 2 portadores del polimorfismo I27L en el gen HNF1α. Métodos: Se incluyó a 31 pacientes diagnosticados previamente y en seguimiento en consultas externas por diabetes tipo MODY 3, MODY 2 y diabetes tipo 2 portadores del polimorfismo I27L en el gen HNF1α: 10 pacientes diagnosticados de diabetes MODY 3 (pertenecientes a 5 familias); 15 pacientes con diabetes MODY 2 (pertenecientes a 9 familias) y 6 pacientes diagnosticados de diabetes tipo 2 portadores del polimorfismo I27L en el gen HNF1α. Se analizan las características clínicas, antropométricas y metabólicas de los pacientes. Resultados: No se objetivaron diferencias en la distribución por sexos y edad o forma de diagnóstico de la diabetes. Todos los pacientes con diabetes MODY 2 y MODY 3 tenían antecedentes familiares de diabetes. El 33,3% de los pacientes con diabetes tipo 2 portadores del polimorfismo I27L en el gen HNF1α no tenían antecedentes familiares de diabetes (p > 0,05). No se encontraron diferencias en el IMC, la prevalencia de hipertensión arterial o la incidencia de complicaciones microvasculares o macrovasculares. En cuanto al tratamiento, el 100% de los pacientes con diabetes MODY 3 necesitaban tratamiento farmacológico. El 100% de los pacientes con diabetes MODY 2 y el 16,7% de los pacientes con diabetes tipo 2 y el polimorfismo I27L en el gen HNF1α no necesitaban tratamiento farmacológico (p > 0,05). Conclusiones: Este artículo realza la dificultad en la correcta clasificación clínica de los pacientes con diabetes MODY 2, MODY 3 y diabéticos tipo 2 con características clínicas atípicas, en este caso portadores del polimorfismo I27L en el gen HNF1α

[Variations in the concentration of the sex hormone binding globulin is a major factor causing a variation in total testosterone values]. / Variaciones en las concentraciones de globulina transportadora de hormonas sexuales como causa importante de alteraciones en las concentraciones de testosterona total.

Measurement of total testosterone concentrations is the initial test for the diagnosis of androgen deficiency or excess in men. However, total testosterone concentrations may be affected by alterations in sex hormone binding globulin (SHBG) concentrations. Most circulating testosterone is bound to SHBG and to albumin and only 0.5-3% of circulating testosterone is unbound or free. The free fraction can be measured by equilibrium dialysis or calculated using published algorithms. The term bioavailable testosterone refers to unbound testosterone plus albumin-bound testosterone; this term reflects the view that, in addition to unbound testosterone, albumin-bound testosterone is readily dissociable and thus bioavailable. Bioavailable testosterone can be measured by precipitation methods or calculated from total testosterone, SHBG, albumin concentrations and their affinity constants. Free testosterone measurements by analog methods are frequently available, but these measurements are affected by alterations in SHBG and are inaccurate. We report the cases of a 42-year-old man with testosterone excess and a 29-year-old man with testosterone deficiency, in whom total testosterone concentrations were affected by SHBG alterations.

Variaciones en las concentraciones de globulina transportadora de hormonas sexuales como causa importante de alteraciones en las concentraciones de testosterona total / Variations in the concentration of sex hormone binding globulin (SHBG) is a major factor causing variations in total testosterone values

La determinación de testosterona total es el primer paso para establecer el diagnóstico de déficit o de exceso de testosterona en varones, pero las concentraciones de testosterona total pueden verse afectadas por un exceso o un déficit de globulina transportadora de hormonas sexuales (SHBG). La mayor parte de la testosterona total circulante se encuentra unida a SHBG y albúmina y sólo el 0,5-3% de la testosterona circulante es testosterona libre. La testosterona libre se puede medir por diálisis en equilibrio o calcularla mediante algoritmos publicados. La testosterona biodisponible hace referencia a la testosterona no unida a proteínas más la testosterona unida a la albúmina; el término biodisponible refleja el hecho de que la testosterona unida a la albúmina es fácilmente disociable. La testosterona biodisponible se puede evaluar por el método de precipitado de SHBG o aproximarnos a su concentración mediante cálculos que utilizan las concentraciones de testosterona total, SHBG, albúmina y sus constantes de afinidad. Debemos tener en cuenta que hay ensayos para determinar testosterona libre que pueden verse afectados por las alteraciones de la SHBG y, por lo tanto, son inadecuados. Presentamos el caso de un varón de 42 años con exceso de testosterona y el de un varón de 29 años con déficit de testosterona, que se debían a la influencia de la testosterona total por la SHBG (AU)

Measurement of total testosterone concentrations is the initial test for the diagnosis of androgen deficiency or excess in men. However, total testosterone concentrations may be affected by alterations in sex hormone binding globulin (SHBG) concentrations. Most circulating testosterone is bound to SHBG and to albumin and only 0.5-3% of circulating testosterone is unbound or free. The free fraction can be measured by equilibrium dialysis or calculated using published algorithms. The term bioavailable testosterone refers to unbound testosterone plus albumin-bound testosterone; this term reflects the view that, in addition to unbound testosterone, albumin-bound testosterone is readily dissociable and thus bioavailable. Bioavailable testosterone can be measured by precipitation methods or calculated from total testosterone, SHBG, albumin concentrations and their affinity constants. Free testosterone measurements by analog methods are frequently available, but these measurements are affected by alterations in SHBG and are inaccurate. We report the cases of a 42-year-old man with testosterone excess and a 29-year-old man with testosterone deficiency, in whom total testosterone concentrations were affected by SHBG alterations (AU)