Insights from the clinical phenotype of subjects with Laron syndrome in Ecuador
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Insights from the clinical phenotype of subjects with Laron syndrome in Ecuador Jaime Guevara-Aguirre 1,2,3 & Camila Bautista 1 & Carlos Torres 1 & Gabriela Peña 1 & Carolina Guevara 1,2 & Cristina Palacios 1 & Alexandra Guevara 2 & Antonio W. D. Gavilanes 3 Accepted: 1 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The Ecuadorian cohort of subjects with LS has taught us valuable lessons since the late 80’s. We have learned about migration of Sephardic Jews to our country, their isolation in remote hamlets and further inbreeding. These geographical, historical and social determinants induced dissemination of a growth hormone (GH) receptor mutation which widely occurred in those almost inaccessible villages. Consequently, the world’s largest Laron syndrome (LS) cohort emerged in Loja and El Oro, two of the southern provinces of Ecuador. We have been fortunate to study these patients since 1987. New clinical features derived from GH insensitivity, their growth patterns as well as treatment with exogenous insulin-like growth factor I (IGF-I) have been reported. Novel biochemical characteristics in the field of GH insensitivity, IGFs, IGF binding proteins (BP) and their clinical correlates have also been described. In the last few years, studies on the morbidity and mortality of Ecuadorian LS adults surprisingly demonstrated that despite obesity, they had lower incidence of diabetes and cancer than their relatives. These events were linked to their metabolic phenotype of elevated but ineffective GH concentrations and low circulating IGF-I and IGFBP-3. It was also noted that absent GH counter-regulation induces a decrease in insulin resistance (IR), which results in low but highly efficient insulin levels which properly handle metabolic substrates. We propose that the combination of low IGF-I signaling, decreased IR, and efficient serum insulin concentrations are reasonable explanations for the diminished incidence of diabetes and cancer in these subjects. Keywords Diabetes-cancer-insulin-IGFI-Ecuadorian Laron syndrome
1 Introduction The Ecuadorian cohort of subjects with Laron syndrome (LSE) provides a unique opportunity to study the largest and most homogenous group with this condition in the world. Moreover, since these observations were done by the same group of investigators, the variability inherent to this type of studies is diminished. These conditions are of even greater relevance when dealing with metabolic studies where nutritional factors play a significant role, especially when considering that meal patterns, and distribution of protein, fat and * Jaime Guevara-Aguirre [email protected] 1
Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador
2
Instituto de Endocrinología IEMYR, Quito, Ecuador
3
Maastricht University, Maastricht, The Netherlands
CHO consumption are different depending on the contextual circumstances of each geographical location. Regarding the LS-E cohort, it should be
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