Frontiers in endocrinology
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Front Endocrinol (Lausanne) · Jan 2019
ReviewThe Discovery and Development of Liraglutide and Semaglutide.
The discovery of glucagon-like peptide-1 (GLP-1), an incretin hormone with important effects on glycemic control and body weight regulation, led to efforts to extend its half-life and make it therapeutically effective in people with type 2 diabetes (T2D). The development of short- and then long-acting GLP-1 receptor agonists (GLP-1RAs) followed. Our article charts the discovery and development of the long-acting GLP-1 analogs liraglutide and, subsequently, semaglutide. ⋯ In summary, rational design has led to the development of two long-acting GLP-1 analogs, liraglutide and semaglutide, that have made a vast contribution to the management of T2D in terms of improvements in glycemic control, body weight, blood pressure, lipids, beta-cell function, and CV outcomes. Furthermore, the development of an oral formulation for semaglutide may provide individuals with additional benefits in relation to treatment adherence. In addition to T2D, liraglutide is used in the treatment of obesity, while semaglutide is currently under investigation for use in obesity and NASH.
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Front Endocrinol (Lausanne) · Jan 2019
Central Precocious Puberty Caused by Novel Mutations in the Promoter and 5'-UTR Region of the Imprinted MKRN3 Gene.
Background: Central Precocious Puberty (CPP) is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. To date, mutations in the coding region of KISS1, KISS1R, PROKR2, DLK1, and MKRN3 genes have been reported as causative for CPP. This study investigated the presence of causative mutations in both the promoter and the 5'-UTR regions of the MKRN3 gene. ⋯ The minimum free energy (MFE) of the mutated 5'-UTR was higher when compared to the corresponding wild-type indicating less stable RNA secondary structure. Conclusion: Our findings demonstrated novel genetic alterations in the promoter and 5'-UTR regulatory regions of the MKRN3 gene. These changes add to another region to check for the etiology of CPP.
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Front Endocrinol (Lausanne) · Jan 2019
Use of Non-invasive Parameters and Machine-Learning Algorithms for Predicting Future Risk of Type 2 Diabetes: A Retrospective Cohort Study of Health Data From Kuwait.
Objective: In recent decades, the Arab population has experienced an increase in the prevalence of type 2 diabetes (T2DM), particularly within the Gulf Cooperation Council. In this context, early intervention programmes rely on an ability to identify individuals at risk of T2DM. We aimed to build prognostic models for the risk of T2DM in the Arab population using machine-learning algorithms vs. conventional logistic regression (LR) and simple non-invasive clinical markers over three different time scales (3, 5, and 7 years from the baseline). ⋯ For all models, the discriminatory power decreased as the prediction horizon increased from 3 to 7 years. Conclusions: Machine-learning techniques represent a useful addition to the commonly reported LR technique. Our prognostic models for the future risk of T2DM could be used to plan and implement early prevention programmes for at risk groups in the Arab population.
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Front Endocrinol (Lausanne) · Jan 2019
Integrative Analysis Toward Different Glucose Tolerance-Related Gut Microbiota and Diet.
Objective: There is evidence that type 2 diabetes (T2DM) is affected by gut microbiota, and gut microbiota diversity modified by diet. To investigate its modifications in Uyghur patients with different glucose tolerance, we enrolled 561 subjects: newly diagnosed T2DM (n = 145), impaired glucose regulation (IGR) patients (n = 138) and in normal control (NC) population (n = 278). Methods: The nutrient intake in food frequency questionnaire was calculated by R language. ⋯ Conclusions: At the phylum and genus level, the structure and diversity of intestinal microbiota of T2DM and IGR was altered, the number of OTUs, the relative abundance, and diversity were all decreased. The gut microbiota of the newly diagnosed T2DM, IGR, and NC were related to age, blood lipids, BMI, blood pressure, and dietary nutrient intake. Unbalanced nutrient intake in the three groups may affect the structure and abundance of the gut microbiota, which may play a role in the occurrence and development of T2DM.
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Front Endocrinol (Lausanne) · Jan 2019
Intermittent Fasting Could Be Safely Achieved in People With Type 1 Diabetes Undergoing Structured Education and Advanced Glucose Monitoring.
Background: Fasting during Ramadan is a form of intermittent fasting in which a person abstains from oral intake between the hours of sunrise and sunset. The fasting month of Ramadan is observed by Muslims worldwide. People with type 1 diabetes (T1DM) who choose to fast during Ramadan are at a particularly high risk of acute diabetes complications including hypoglycemia and significant hyperglycemia. ⋯ No episodes of severe hypoglycemia, DKA, acute kidney injury, or hospitalization occurred during Ramadan period. Percentage time spent >10 mmol/L (46.7 ± 17.7% vs. 42.5 ± 16.4%, p = 0.03) was significantly increased, and percentage time [range, 4-10 mmol/L (48.8 ± 15.9% vs. 50.9 ± 15.9%, p = 0.13)] and percentage time spent <4 mmol/L (4.7 ± 5.4.7% vs. 5.7 ± 6.3%, p = 0.09) were reduced, but these differences were not significant. Conclusions: People with uncomplicated T1DM could safely participate in intermittent fasting similar to Ramadan fasting if equipped with structured education and advanced glucose monitoring systems.