Therapeutic Advances in Endocrinology and Metabolism最新文献

Background: The prevalence of type 2 diabetes mellitus (T2DM) continues to increase; the clinical practice guidelines continue to modify the recommendations for its treatment.

Objective: The aim was to determine the prescription patterns of noninsulin antidiabetics in a group of patients from Colombia.

Design: Cross-sectional study.

Methods: The use of noninsulin antidiabetic drugs based on a population database of patients under treatment in 2022. Comorbidities were identified, including total numbers, proportions, and defined daily doses of each antidiabetic agent per 1000 inhabitants/day (DHD).

Results: A total of 155,381 patients with T2DM were identified, with a mean age of 67.1 ± 12.0 years. The most widely used antidiabetics according to DHD were metformin (9.46 DHD), empagliflozin (5.3), sitagliptin (2.8), linagliptin (2.4), and dapagliflozin (2.3), mainly in combination therapy (55.5%), most often two (31.2% of patients) or three antidiabetics (22.4% of patients). The most frequent cardiovascular comorbidities were hypertension (67.6%), chronic kidney disease (6.3%), and coronary ischemic heart disease (2.5%), treated with angiotensin 2 receptor antagonists, followed by diuretics, calcium antagonists, and β-blockers.

Conclusion: This group of patients with T2DM has been treated mainly with metformin alone or in combination with other antidiabetic drugs, but despite the changes in treatment in recent years, a significant number of patients with concomitant cardiovascular conditions are not receiving appropriate antidiabetic agents. Sodium-glucose type 2 cotransporter or glucagon-like peptide-1 receptor agonists may offer additional benefits with reduced cardiovascular risk.

As the prevalence of obesity continues to rise globally, the research on adipocytes has attracted more and more attention. In the presence of nutrient overload, adipocytes are exposed to pressures such as hypoxia, inflammation, mechanical stress, metabolite, and oxidative stress that can lead to organelle dysfunction. Endoplasmic reticulum (ER) is a vital organelle for sensing cellular pressure, and its homeostasis is essential for maintaining adipocyte function. Under conditions of excess nutrition, ER stress (ERS) will be triggered by the gathering of abnormally folded proteins in the ER lumen, resulting in the activation of a signaling response known as the unfolded protein responses (UPRs), which is a response system to relieve ERS and restore ER homeostasis. However, if the UPRs fail to rescue ER homeostasis, ERS will activate pathways to damage cells. Studies have shown a role for disturbed activation of adipocyte ERS in the pathophysiology of obesity and its complications. Prolonged or excessive ERS in adipocytes can aggravate lipolysis, insulin resistance, and apoptosis and affect the bioactive molecule production. In addition, ERS also impacts the expression of some important genes. In view of the fact that ERS influences adipocyte function through various mechanisms, targeting ERS may be a viable strategy to treat obesity. This article summarizes the effects of ERS on adipocytes during obesity.

Background: Recombinant human growth hormone (rhGH, somatropin) therapy is approved in children with Prader-Willi syndrome (PWS).

Objectives: To report safety and effectiveness data for children with PWS treated with biosimilar rhGH (Omnitrope^®, Sandoz) in the PAtients TReated with Omnitrope (PATRO) Children study.

Design: PATRO Children was a multicenter, non-interventional, postmarketing surveillance study.

Methods: Children with PWS received Omnitrope according to standard clinical practice. Adverse events (AEs) were monitored for the duration of Omnitrope treatment. Effectiveness outcomes were also assessed, including height standard deviation (SD) scores (HSDS).

Results: As of July 2020 (study completion), 235 patients with PWS had been enrolled. At baseline, 95.7% (n = 225) of patients were prepubertal and 86.4% (n = 203) were rhGH treatment-naïve. At analysis, the median (range) treatment duration in the study was 56.8 (2.9-155.8) months. AEs were reported in 192 patients (81.7%) and were suspected as treatment-related in 39 patients (16.6%). Serious AEs (SAEs) were reported in 96 patients (40.9%) and were suspected as treatment-related in 22 patients (9.4%). The most frequent treatment-related SAEs were sleep apnea syndrome (n = 11; 4.7%), tonsillar hypertrophy (n = 4; 1.7%), and adenoidal hypertrophy (n = 4; 1.7%). Development of scoliosis was considered treatment-related in two patients; development of impaired glucose tolerance in one patient and type 2 diabetes mellitus in another patient were considered treatment-related. Effectiveness outcomes were primarily assessed in 153 patients who completed 3 years of treatment. Among the 151 prepubertal patients (135 treatment-naïve), mean (SD) change from baseline in HSDS after 3 years was +1.50 (1.07) across all patients and +1.57 (1.07) for treatment-naïve patients.

Conclusion: These data suggest that biosimilar rhGH is well tolerated and effective in patients with PWS managed in real-life clinical practice. Patients with PWS should continue to be closely monitored for well-known safety issues (including respiratory, sleep, and glucose metabolism disorders, and scoliosis) during rhGH treatment.

Background: Metabolic syndrome involves health problems influenced by aging and genetics. The glucokinase regulatory protein (GCKR) rs1260326 polymorphism (Leu446) is associated with metabolic traits. This study explores the impact of the GCKR rs1260326 polymorphism on metabolic traits in older Japanese with focusing on sex-specific differences.

Methods: This cross-sectional study from the Bunkyo Health Study in Tokyo, Japan, examined 883 participants aged 65-84 years. Participants were excluded with diabetes, or on drug treatment for diabetes or dyslipidemia. The GCKR P446L polymorphism was analyzed and compared their characteristics of physical activity, dietary intake, body composition, and metabolic parameters.

Results: Study participants with GCKR rs1260326 genotypes (C/C 20.7%, C/T 47.6%, T/T 31.7%) had a median age of 72 years, and 60.4% were women. Men with the T/T genotype, as compared to the C/C genotype, had a lower body weight, body mass index (BMI), and skeletal mass index. This genotype also associated with lower fasting insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), and higher Matsuda index, but not after adjustment for age, BMI, and physical activity. In contrast, women with the T/T genotype, compared to the C/C genotype, showed higher C-reactive protein, fibroblast growth factor 21, and Matsuda index. They also had lower fasting insulin, insulin area under the curve, and HOMA-IR; with these associations being independent of age, BMI, and physical activity.

Conclusion: The GCKR rs1260326 genotype-affected metabolic traits differentially by sex in older Japanese. This highlights the need to consider sex differences in GCKR-related metabolic outcomes.

The term metabolic-associated fatty liver disease (MAFLD), with a global prevalence estimated at 38.77%, has gradually replaced the traditional concept of non-alcoholic fatty liver disease (NAFLD). Compared to the general population, the incidence of MAFLD is notably higher among pregnant women, posing potential risks to both maternal and neonatal health. This review summarizes the latest research on MAFLD, focusing on its association with pregnancy complications. Additionally, it provides a comparative analysis with previous studies on NAFLD, presenting a comprehensive perspective for clinical management. Findings suggest that pregnant women with MAFLD face a higher risk of gestational hypertension and cesarean delivery compared to those with NAFLD, while the risk for gestational diabetes mellitus remains similar between the two conditions. Additionally, MAFLD is associated with an increased likelihood of delivering large-for-gestational-age infants and heightened risks of preterm birth and low birth weight. Current treatment strategies for MAFLD focus on lifestyle modifications, such as dietary adjustments and increased physical activity. However, there is an urgent need for the development of safe and effective pharmacological treatments, particularly tailored toward pregnant women. Future research should delve deeper into the causal relationships between MAFLD and pregnancy complications and explore optimal therapeutic approaches to improve outcomes for mothers and their infants.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver condition affecting 25%-40% of the worldwide population. NAFLD is traditionally related to obesity and metabolic disorders. NAFLD can also affect non-obese individuals, termed "lean NAFLD" (LN), who exhibit a paradoxical combination of physical leanness and metabolic obesity. Factors contributing to LN remain unclear, necessitating further research. This analysis aims to understand LN's prevalence and metabolic characteristics compared to obese NAFLD (ON) populations.

Methods: This meta-analysis searched various databases until August 1, 2023. Inclusion criteria involved observational studies comparing LN with overweight/obese NAFLD. Data extraction included baseline characteristics, disease occurrence, metabolic profile, and clinical parameters-statistical analysis employed calculating risk ratios (RR) and standard mean differences.

Results: Twenty-five studies were analyzed. LN is associated with lower prevalence in both NAFLD (RR 0.27, 95% confidence interval (CI) 0.14-0.52, p = <0.0001) and total (RR 0.27, 95% CI 0.15-0.51, p < 0.0001) population. LN had lower diabetes mellitus (RR 0.78, 95% CI 0.71-0.87, p < 0.00001), dyslipidemia (RR 0.87, 95% CI 0.79-0.95, p = 0.002), hypertension (RR 0.80, 95% CI 0.74-0.87, p < 0.00001), and metabolic syndrome (RR 0.45, 95% CI 0.31-0.64, p < 0.00001) compared to those with ON. The LN group's lipid profile, blood pressure, and other clinical parameters were favorable compared to ON.

Conclusion: The prevalence of NAFLD among lean and non-lean individuals varies by region. Our analysis revealed that LN is associated with lower metabolic diseases, fasting blood sugar, blood pressure, and a more favorable lipid profile compared to ON.

Objective: Intermittently scanned continuous glucose monitoring (isCGM) has revolutionised the care of people with diabetes but its uptake and benefits in older adults are not well known. We examined the impact of isCGM (Freestyle Libre, FSL) on glycaemic outcomes in younger (⩽65 years) and older adults (>65 years) with diabetes.

Design and methods: In total, 2260 adult patients registered on the Libreview account at University Hospitals Birmingham NHS Foundation Trust, UK, were included. Inclusion criteria: all patients with type 1 and type 2 diabetes aged >18 years, use of isCGM >6 months, scanning at least 6 times/day. Demographics, diabetes history and glycaemic outcomes (time in range (TIR), time above range and time below range (TBR), estimated HbA1c, HbA1c at start and at end of study) were collected by accessing electronic patient records and Libreview. Outcomes were compared between age groups ⩽65 or >65 years old.

Results: Most patients were of Caucasian ethnicity (⩽65 years 68%, >65 years 73%) and had type 1 diabetes. Mean duration of diabetes was 19.5 years (range 0-65 years) and 34.5 years (range 0-79 years) for ⩽65 and >65 years, respectively. Only a quarter of those ⩽65 years achieved (219/943; 23.2%) their age specific TIR target compared to 69% (78/113) of those >65 years cohort, while 70.1% (663/946) of ⩽65 years and 40.7% (46/113) of >65 years achieved their age-specific TBR target. When the less strict ⩽65 years TBR target was applied, 75% (85/113) of >65 years cohort achieved this.

Conclusion: FSL use was associated with improved glycaemic outcomes across all age groups. Individualised targets may be needed to improve TBR in those aged >65 years.

Background: Fat distribution plays an important role in impaired glucose tolerance. Android adiposity (ANDROID) and gynoid adiposity (GYNOID) have been proven to be linked with insulin resistance. A higher risk of sarcopenia is associated with type 2 diabetes mellitus (T2DM). In this study, ANDROID, GYNOID, and ANDROID to GYNOID ratios (A/G ratios) were evaluated in T2DM patients to determine if they were associated with sarcopenia.

Methods: We recruited 1086 T2DM patients, measured skeletal muscle index (SMI), ANDROID, GYNOID, and collected clinical data.

Results: T2DM patients with 119 male subjects had sarcopenia (20.24%), and 72 female subjects had sarcopenia (16.51%). All patients with T2DM who had high ANDROID and A/G ratios were at a reduced risk of sarcopenia. The SMI showed a correlation with ANDROID and A/G ratios among subjects with T2DM.

Conclusion: ANDROID and A/G ratios are inversely related to sarcopenia in T2DM patients.