Expert Review of Endocrinology & Metabolism最新文献

Introduction: Achondroplasia is a heritable disorder of the skeleton that affects approximately 300,000 individuals worldwide. Until recently, treatment for this condition has been purely symptomatic. Efficacious treatment options for children are now approved or are in clinical trials.

Areas covered: This review discusses key advances in the therapeutic management of children with achondroplasia, including vosoritide, the first approved drug, and other emerging precision therapies. These include navepegritide, a long-acting form of C-type natriuretic peptide, and infigratinib, a tyrosine kinase receptor inhibitor, summarizing trial outcomes to date.

Expert opinion: The advent of the first approved precision therapy for achondroplasia in vosoritide has been a paradigm shifting advance for children affected by this condition. In addition to changing their natural growth history, it is hoped that it will decrease their medical complications and enhance functionality. These new treatment options highlight the importance of prompt prenatal identification and subsequent testing of a suspected fetus with achondroplasia and counseling of families. It is hoped that, in the near future, families will have the option to consider a range of effective targeted therapies that best suit their child with achondroplasia, starting from birth should they choose.

Objective: Time in Tight Range (TITR), defined as the percentage of time within the glucose range of 70 to 140 mg/dL, is anticipated to be challenging to maintain without causing hypoglycemia, especially in individuals with type 1 diabetes (T1D). This study aimed to investigate the TITR target value in individuals with T1D on multiple daily injections (MDI).

Methods: The study included 101 individuals with T1D on MDI aged 15 to 75 who were hospitalized at Jikei University School of Medicine from September 2006 to November 2013 to conduct Continuous Glucose Monitoring (CGM). The cutoff values of TITR for predicting the attainment of GMI < 7.0%, and TBR < 4% were determined using Receiver Operating Characteristic (ROC) curves.

Results: The TITR cutoff value was calculated to be 41% (sensitivity 81%, specificity 88%) and 40% (54%,72%) for predicting GMI < 7.0% and TBR < 4%.

Conclusions: In individuals with T1D on MDI without devices capable of preventing hypoglycemia, it is recommended to target TITR at 40% to address the risk of increased hypoglycemia sufficiently.

Introduction: Incretin-based therapies have emerged as effective treatments for type 2 diabetes (T2D) and obesity. However, not all patients achieve optimal outcomes with existing treatments, highlighting the need for more effective solutions.

Areas covered: We present a comprehensive evaluation of Tirzepatide (TZP), a novel dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonist, for managing obesity and T2D. We conducted a systematic search of Cochrane, PubMed, Scopus, and Web of Science databases from inception to April 2024. The focus of the review is on the development and therapeutic potential of TZP, with detailed exploration on pharmacodynamics, pharmacokinetics, clinical efficacy, and safety. Furthermore, it reviews TZP's impacts on glycemic control, weight management, and its potential cardiovascular (CV) benefits.

Expert opinion: TZP represents a significant advancement in the dual-targeted approach to treating T2D and obesity. Its unique mechanism of action offers superior efficacy in reducing glycemic levels and body weight compared to existing therapies. New data suggesting improvements in CV outcomes indicate that TZP could set a new standard in the treatment paradigm. While long-term data on efficacy and safety are still forthcoming, current evidence positions TZP as a promising option for patients who have not reached their therapeutic goals with existing treatments.

Background: According to previous reports, very high percentages of individuals in Saudi Arabia are undiagnosed for type 2 diabetes mellitus (T2DM). Despite conducting several screening and awareness campaigns, these efforts lacked full accessibility and consumed extensive human and material resources. Thus, developing machine learning (ML) models could enhance the population-based screening process. The study aims to compare a newly developed ML model's outcomes with the validated American Diabetes Association's (ADA) risk assessment regarding predicting people with high risk for T2DM.

Research design and methods: Patients' age, gender, and risk factors that were obtained from the National Health Information Center's dataset were used to build and train the ML model. To evaluate the developed ML model, an external validation study was conducted in three primary health care centers. A random sample (N = 3400) was selected from the non-diabetic individuals.

Results: The results showed the plotted data of sensitivity/100-specificity represented in the Receiver Operating Characteristic (ROC) curve with an AROC value of 0.803, 95% CI: 0.779-0.826.

Conclusions: The current study reveals a new ML model proposed for population-level classification that can be an adequate tool for identifying those at high risk of T2DM or who already have T2DM but have not been diagnosed.

Introduction: Obesity is a growing public health concern affecting both children and adults. Since it involves both genetic and environmental components, the management of obesity requires both, an understanding of the underlying genetics and changes in lifestyle. The knowledge of obesity genetics will enable the possibility of precision medicine in anti-obesity medications.

Areas covered: Here, we explore health complications and the prevalence of obesity. We discuss disruptions in energy balance as a symptom of obesity, examining evolutionary theories, its multi-factorial origins, and heritability. Additionally, we discuss monogenic and polygenic obesity, the converging biological pathways, potential pharmacogenomics applications, and existing anti-obesity medications - specifically focussing on the leptin-melanocortin and incretin pathways. Comparisons between childhood and adult obesity genetics are made, along with insights into structural variants, epigenetic changes, and environmental influences on epigenetic signatures.

Expert opinion: With recent advancements in anti-obesity drugs, genetic studies pinpoint new targets and allow for repurposing existing drugs. This creates opportunities for genotype-informed treatment options. Also, lifestyle interventions can help in the prevention and treatment of obesity by altering the epigenetic signatures. The comparison of genetic architecture in adults and children revealed a significant overlap. However, more robust studies with diverse ethnic representation is required in childhood obesity.

Background: To assess 20-year time trends in the prevalence of diabetes mellitus (DM) among inpatients with heart failure (HF) and the influence of coexisting DM and kidney disease (KD) on outcomes.

Research design and methods: A retrospective study of patients was admitted due to HF, during the period 2000/2019. The period of follow-up was divided into three intervals according to the European Medical Agency approval of newer hypoglycemic drugs. We analyzed in-hospital mortality and outcomes during the follow-up period.

Results: A total of 4959 patients were included. Over time, prevalence of DM was significantly raising among women with HF (50 to 53.2%) and descending among men (50% to 46.8%, p = 0.02). Total mortality and readmissions were higher in patients with DM during the and second periods. However, no significant differences were found in the third-one (HR 1.14, 95% CI 0.94-1.39, p = 0.181). A protector role of oral hypoglycemic medications was observed in this last period. According to the presence of KD, the patients with both DM and KD were who presented most of the events.

Conclusions: Over the time analyzed, the prevalence of DM raised among women and decreased among men. DM influenced the prognosis of HF except in the third period when more protective hypoglycemic drugs started to be used.

Background: Type 1 diabetes mellitus (T1DM) is associated with adverse maternal and fetal outcomes. Continuous glucose monitoring (CGM) during pregnancy is associated with better glycemic control in women with T1DM. However, no clear benefits have been demonstrated in reducing adverse feto-maternal outcomes in pregnant women with T1DM.

Design and methods: This is a retrospective, single-center study of pregnant women with T1DM to evaluate the impact of CGM use on glycemic control and feto-maternal outcomes in pregnant women with T1DM.

Results: Of 265 women with T1DM, 92 (34.7%) used CGM, and 173 (65.3%) were managed with capillary blood glucose (CBG) monitoring. The mean (SD) age and BMI at the first visit were 29.4 (4.7) years and 27.2 (5.2) kg/m^2, respectively. The mean (SD) HbA1c at the first-trimester visit was 63 (1) mmol/mol, and in the last trimester was 51 (1%). There was no difference in the mean changes in HbA1c between the two groups. Women using CGM had lower insulin requirements (1.02 + 0.37 vs. 0.87 + 0.04 units/kg, p = 0.01). The two groups had no significant differences in maternal or fetal outcomes.

Conclusion: CGM use in pregnant T1DM women is not associated with improved fetomaternal outcomes.

Introduction: Post-pancreatitis diabetes mellitus (PPDM) has long been recognized as one of the most challenging sub-types of diabetes to manage. Part of the problem is that the earlier literature on epidemiology of PPDM was confusing because of the presence of selection bias.

Areas covered: A concerted series of population-based nationwide studies on PPDM from New Zealand has recently been published as part of the COSMOS (Clinical and epidemiOlogical inveStigations in Metabolism, nutritiOn, and pancreatic diseaseS) program and is the main focus of the present article.

Expert opinion: The foundational knowledge on epidemiology of PPDM generated by the COSMOS program is generalizable to the population at large. It brings the field closer to a comprehensive narrative of risk factors, burden, mortality, and morbidity outcomes of PPDM. In producing new knowledge on epidemiology of PPDM, it will be important to adhere to the guidelines on identification of PPDM in population-based datasets advanced in the present article.

Background: Determining the relationship between cardiovascular risks, carbohydrate metabolism disorders, and renal dysfunction can help in creating new tools for their management and for better interaction of specialists in a multidisciplinary team. The purpose of this study was to determine the functional state of the kidneys and carbohydrate metabolism in patients with acute coronary syndrome without a history of such disorders.

Methods: 200 patients of the cardiology department of the City Clinical Hospital No. 7 in Almaty were examined using laboratory diagnostics and subsequent statistical data processing.

Results: Acute coronary syndrome develops in 63% of cases against the background of previous disorders of carbohydrate metabolism - prediabetes (45.5%) and type 2 diabetes mellitus (17.5%). In this group of patients, in the presence of disorders of carbohydrate metabolism, in all cases, it is accompanied by acute renal damage. It was noted that diabetes mellitus in newly diagnosed patients actually had a certain duration and occurred much earlier than cardiovascular complications - this was evidenced by an increased level of glycated hemoglobin.

Conclusions: Such results indicate the need for early diagnosis of cardio-reno-metabolic syndrome in patients with cardiovascular complications, as well as timely administration of drugs that simultaneously have antidiabetic, cardio- and nephroprotective effects.