Implication of Pappalysins and Stanniocalcins in the Bioavailability of IGF-I in Children With Type 1 Diabetes Mellitus.

Context: Anomalies in the growth hormone (GH)/insulin-like growth factor (IGF) axis, are common in children with type 1 diabetes mellitus (T1DM), even in those reaching a normal or near-normal final height. However, concentrations of the IGF bioavailability regulatory factors (pappalysins [PAPP-As] and stanniocalcins [STCs]) have not been reported in children with T1DM. Objective: To determine serum concentrations of PAPP-As and STCs in children at diagnosis of T1DM and after insulin treatment and the correlation of these factors with other members of the GH/IGF axis, beta-cell insulin reserve, auxology, and nutritional status. Methods: A single-center prospective observational study including 47 patients (59.5% male), with T1DM onset at median age of 9.2 years (interquartile range: 6.3, 11.9) was performed. Blood and anthropometric data were collected at diagnosis and after 6 and 12 months of treatment. Results: At 6 and 12 months after T1DM diagnosis, there was improvement in the metabolic control (decrease in glycated hemoglobin [HbA1c] at 12 months -3.66 [95% CI: -4.81, -2.05], P = .001), as well as in body mass index SD and height SD (not statistically significant). STC2 increased (P < .001) and PAPP-A2 decreased (P < .001) at 6 and 12 months of treatment onset (P < .001), which was concurrent with increased total IGF-I and IGF-binding protein concentrations, with no significant modification in free IGF-I concentrations. HbA1c correlated with PAPP-A2 (r = +0.41; P < .05) and STC2 (r = -0.32; P < .05). Conclusion: Implementation of insulin treatment after T1DM onset modifies various components of the circulating IGF system, including PAPP-A2 and STC2. How these modifications modulate linear growth remains unknown.

La respuesta monofásica a la sobrecarga oral de glucosa como factor predictivo del riesgo de diabetes tipo 2 en pacientes pediátricos con obesidad / The monophasic pattern in oral glucose tolerance test as a predictive risk factor of type 2 diabetes in obese paediatric patients

Introducción: El aumento en la prevalencia de obesidad en la edad pediátrica se asocia a mayor incidencia de diabetes mellitus tipo2 (DM2). El tipo de respuesta de la glucemia y de la insulina a la sobrecarga oral de glucosa (SOG) podría predecir el riesgo de DM2 en pacientes con obesidad. Objetivo: Valorar la respuesta a la SOG y relacionar con factores de riesgo de DM2 en niños y adolescentes obesos. Métodos: Estudio observacional retrospectivo sobre 588 pacientes (309 varones, 279 mujeres); 90,3% caucásicos; edad media 11,1 ± 2,8 años. Según el tipo de respuesta en la SOG se establecieron dos grupos: monofásico y bifásico. Se analizaron parámetros antropométricos, bioquímicos e índices relacionados con sensibilidad a la insulina y la función de la célula Beta. Resultados: El 50,2% de los pacientes tuvieron un patrón de glucosa monofásico (50,8% varones), el 48,5% bifásico (47,6% varones) y el 1,3% indeterminado. La respuesta monofásica mostró menor sensibilidad a la insulina y peor función de la célula Beta; los pacientes con patrón bifásico presentaron mayor índice de masa corporal, perímetro de cintura y presión arterial, sin ser estos resultados estadísticamente significativos. Los pacientes latinos tuvieron glucemias significativamente menores en la SOG a expensas de una mayor insulinemia. Conclusiones: El patrón de respuesta de la SOG refleja fenotipos metabólicos diferentes. Los pacientes pediátricos con un patrón bifásico tienen un perfil con menor riesgo de desarrollar DM2. Una SOG en niños y adolescentes obesos podría ser útil para implementar estrategias de intervención precoz y prevenir la aparición de prediabetes o DM2 en esta población (AU)

Introduction: The onset of obesity at young ages is strongly associated with the early development of type 2 diabetes (T2D). The shape of the curves of glucose and insulin curves during an oral glucose tolerance test (OGTT) could predict the risk of developing T2D. Objective: To analyse the morphology of the OGTT and determine T2D risk factors in a mainly Caucasian population of children and adolescents. Methods: Observational retrospective study including 588 patients (309 males, 279 females) with a mean age of 11.1 ± 2years, and of whom 90.3% were Caucasian. Risk factors for T2D were compared in patients with a monophasic or biphasic pattern during the performance of an OGTT, as well as anthropometric and biochemical variables, insulin resistance, and beta-cell function. Results: The shape of the glucose curve was monophasic in 50.2% of patients (50.8% male), biphasic in 48.5% (47.6% males), and indeterminate in 1.3%. The monophasic pattern showed lower insulin-sensitivity and worse beta-cell function. Patients with a biphasic pattern had a higher BMI, waist circumference, and blood pressure, although the results were not significant. Latin-American patients had significantly lower serum glucose levels with higher insulin levels during the OGTT. Conclusions: The pattern of response to an OGTT reflects different metabolic phenotypes. Paediatric patients with a biphasic pattern have lower risk-profiling for T2D. The performing of an OGTT could be useful to implement early intervention strategies in children and adolescents with obesity, in order to prevent the development of pre-diabetes or T2D (AU)

[The monophasic pattern in oral glucose tolerance test as a predictive risk factor of type 2 diabetes in obese paediatric patients]. / La respuesta monofásica a la sobrecarga oral de glucosa como factor predictivo del riesgo de diabetes tipo 2 en pacientes pediátricos con obesidad.

INTRODUCTION: The onset of obesity at young ages is strongly associated with the early development of type 2diabetes (T2D). The shape of the curves of glucose and insulin curves during an oral glucose tolerance test (OGTT) could predict the risk of developing T2D. OBJECTIVE: To analyse the morphology of the OGTT and determine T2D risk factors in a mainly Caucasian population of children and adolescents. METHODS: Observational retrospective study including 588 patients (309 males, 279 females) with a mean age of 11.1±2years, and of whom 90.3% were Caucasian. Risk factors for T2D were compared in patients with a monophasic or biphasic pattern during the performance of an OGTT, as well as anthropometric and biochemical variables, insulin resistance, and beta-cell function. RESULTS: The shape of the glucose curve was monophasic in 50.2% of patients (50.8% male), biphasic in 48.5% (47.6% males), and indeterminate in 1.3%. The monophasic pattern showed lower insulin-sensitivity and worse beta-cell function. Patients with a biphasic pattern had a higher BMI, waist circumference, and blood pressure, although the results were not significant. Latin-American patients had significantly lower serum glucose levels with higher insulin levels during the OGTT. CONCLUSIONS: The pattern of response to an OGTT reflects different metabolic phenotypes. Paediatric patients with a biphasic pattern have lower risk-profiling for T2D. The performing of an OGTT could be useful to implement early intervention strategies in children and adolescents with obesity, in order to prevent the development of pre-diabetes or T2D.

Achievement of metabolic control goals set by the American Diabetes Association and the International Society for Pediatric and Adolescent Diabetes in pediatric patients with type 1 diabetes from Spain.

AIM: The "T1D Exchange Clinic Registry" of 13.316 pediatric patients with type 1 diabetes (T1D) in U.S. recently revealed that most children have HbA1c values above target levels established by the American Diabetes Association (ADA) and the International Society for Pediatric and Adolescent Diabetes (ISPAD). The aim of this study is to assess the proportion of youngsters with T1D who meet the internationally accepted targets for good metabolic control of diabetes at a single, referral Pediatric Diabetes Center in Spain. PATIENTS AND METHODS: Cross-sectional study of 236 children and adolescents with T1D controlled at our Pediatric Diabetes Unit. We analyzed the compliance to metabolic goals set by ADA and ISPAD and the differences between patients treated with continuous subcutaneous insulin infusion and multiple daily injections. STATISTICS: SPSS™ version 21.0. RESULTS: Mean age: 12.6 ± 4.6 years old, mean age at diagnosis: 6.1 ± 4.3 years old and mean diabetes duration: 6.4 ± 4.3 years; 47% female. HbA1c average: 6.7 ± 0.7% (49.7 ± 7.6 mmol/mol). The age-specific ADA and ISPAD HbA1c targets were achieved by 93% and 91% of patients, respectively. Among pump users, 97%/97% met ADA/ISPAD HbA1c targets compared to 87%/88% of MDI users (p = 0.04/p = 0.03), without significant differences in the analysis by groups of age. Among participants, 95%, 62%, 95%, 98% and 89% met HDLc, LDLc, triglycerides, BP and BMI targets. CONCLUSIONS: Most patients in our children and adolescent cohort of T1D patients correctly achieve metabolic goals established by ADA and ISPAD with low incidence of hypoglycemia.