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Obesity affects a significant fraction of the world population, with some states or countries reporting overwhelming majority of the population as obese or overweight. Effective treatments were not readily available until the recent approval of glucagon-like peptide-1 (GLP-1) -based pharmacotherapeutics for weight loss. Since then, the use of GLP-1-based pharmacotherapies for the treatment of obesity has skyrocketed. In addition to or because of the effective weight loss, these medications affect many different organs in the body. Many of these effects, including the degree of weight loss achieved, show significant sex differences. Moreover, recent analysis of online patient communities identified a range of self-reported reproductive and endocrine side effects of GLP-1 based therapies including menstrual irregularities, reduced libido, and hot-flashes that have not been systematically captured in clinical trials. Some of these reports contrast with recent data indicating that in Polyendocrine Metabolic Ovarian Syndrome (PMOS; formerly Polycystic Ovary Syndrome) patients semaglutide-associated weight loss normalizes menstrual cycles in most patients, leaving this issue unresolved. While it has been established that sex and sex hormones affect the action of GLP-1 analogues, whether these medications affect the levels of sex hormones and reproductive organs is less well understood, especially in a chronic and clinically relevant drug application setting.

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Genetics of type 2 diabetes: Beyond single nucleotide variant studies

Celeste Moya-Valera, Mariana de Jesus Gallardo-Espinoza, Alex Fernando Arita, Francisco Lara-Hernandez, ... Felipe Javier Chaves

Genetics of type 2 diabetes: Beyond single nucleotide variant studies

Type 2 Diabetes (T2D) is a complex disease that has increased in prevalence in the last years affecting over 530 million people around the world. T2D increases mortality and morbidity by different mechanisms. As a complex disease, it is caused by many genetic changes and, consequently, T2D genetics has been analyzed from different points of view and using different strategies. Most studies have focused on inherited Single Nucleotide Variants (SNVs) present in genomic DNA, while other types of genetic variants have received less attention.

The aim of the present review is to examine the limitations of the studies conducted to date, and the importance of non-SNVs and non-germinal variants in the genetics of this disease. In this way, structural variants, mobile elements and tandem repeats have a crucial role in T2D. In addition, variations in mitochondrial DNA and somatic variations have been shown to play an important role in metabolic alterations that may lead to the development of T2D.

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Genetics of type 2 diabetes: Beyond single nucleotide variant studies

Celeste Moya-Valera, Mariana de Jesus Gallardo-Espinoza, Alex Fernando Arita, Francisco Lara-Hernandez, ... Felipe Javier Chaves

Genetics of type 2 diabetes: Beyond single nucleotide variant studies

Type 2 Diabetes (T2D) is a complex disease that has increased in prevalence in the last years affecting over 530 million people around the world. T2D increases mortality and morbidity by different mechanisms. As a complex disease, it is caused by many genetic changes and, consequently, T2D genetics has been analyzed from different points of view and using different strategies. Most studies have focused on inherited Single Nucleotide Variants (SNVs) present in genomic DNA, while other types of genetic variants have received less attention.

The aim of the present review is to examine the limitations of the studies conducted to date, and the importance of non-SNVs and non-germinal variants in the genetics of this disease. In this way, structural variants, mobile elements and tandem repeats have a crucial role in T2D. In addition, variations in mitochondrial DNA and somatic variations have been shown to play an important role in metabolic alterations that may lead to the development of T2D.

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