Journal of Clinical and Translational Endocrinology最新文献

Multiple randomized controlled trials have extensively examined the therapeutic effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors, ushering in a transformative approach to treating individuals with type 2 diabetes mellitus (DM). Notably, emerging reports have drawn attention to the potential positive impacts of SGLT2 inhibitors in nondiabetic patients. In an effort to delve into this phenomenon, a comprehensive systematic literature review spanning PubMed (NLM), Medline (Ovid), and Cochrane Library, covering publications from 2000 to 2024 was undertaken. This systematic review encompassed twenty-six randomized control trials (RCTs) involving 35,317 participants. The findings unveiled a multifaceted role for SGLT2 inhibitors, showcasing their ability to enhance metabolic control and yield cardioprotective effects through a reduction in cardiovascular death (CVD) and hospitalization related to heart failure (HF). Additionally, a renalprotective effect was observed, evidenced by a slowdown in chronic kidney disease (CKD) progression and a decrease in albuminuria. Importantly, these benefits were coupled with an acceptable safety profile. The literature also points to various biological plausibility and underlying mechanistic pathways, offering insights into the association between SGLT2 inhibitors and these positive outcomes in nondiabetic individuals. Current research trends indicate a continual exploration of additional role for SGLT2 inhibitors in. Nevertheless, further research is imperative to fully elucidate the mechanisms and long-term outcomes associated with the nondiabetic use of SGLT2 inhibitors.

Introduction

Human papillomavirus (HPV) causes 99.7% of cervical cancer cases. Cervical cancer is preventable through early detection via HPV testing. However, the number of women screened for cervical cancer has not increased in the last several years. Lower screening rates among women living in high poverty and social vulnerability areas, Black women, and women with chronic co-morbidities (e.g., type 2 diabetes (T2D)) are associated with their higher cervical cancer mortality rates. When screened, Black women are more likely to be diagnosed at later stages and die from cervical cancer. HPV self-collection decreases barriers to cervical cancer screening and can help lessen disparities among underserved women. This study aimed to examine the acceptability of HPV self-collection among Black women with T2D living in socially vulnerable communities.

Methods

Qualitative semi-structured interviews were conducted with 29 Black women with T2D living in communities with high social vulnerability. The Health Belief Model informed the development of the interview guide to gather data on the acceptability of HPV self-collection.

Results

Three main themes aligned with the Health Belief Model were identified: (1) HPV self-collection provides a comfortable alternative to in-clinic HPV testing (perceived benefits); (2) HPV self-collection would result in awareness of current HPV status (health motivation); and (3) Women were concerned about collecting their sample accurately (perceived barriers).

Discussion/Conclusion

Black women with T2D living in communities with high social vulnerability identified multiple benefits of cervical cancer screening through HPV self-collection. Women are concerned about their ability to collect these samples correctly. Our findings call for future studies focusing on increasing self-efficacy and skills to collect HPV samples among Black women with chronic conditions like T2D who reside in underserved communities with high social vulnerability.

Objective

Patients with Cystic Fibrosis related diabetes [CFRD] are treated with insulin and high calorie diets to maintain body mass. The combined CFTR modulator elexacaftor/tezacaftor/ivacaftor [ETI] decreases pulmonary exacerbations and improves nutritional status. We reviewed the effects of ETI on BMI, HbA1c and diabetes regimen in patients with CFRD over a period of three years.

Methods

Data of previously CFTR-modulator-naïve patients with CFRD and pancreatic insufficiency on ETI therapy were retrieved from an electronic health record database. Patients were followed for a mean duration of 2.7 ± 0.8 years after ETI initiation. Data pertaining to weight, BMI, HbA1c and diabetes regimen were collected at 6 months, 12 months, 2 years and at 3 years post-ETI initiation. Patients were then dichotomized based on their baseline BMI into a low BMI group and an “at target” BMI group. The effects of ETI on changes in weight, BMI, A1c and diabetes regimen were compared in both groups over a period of three years.

Results

Twenty-seven patients with CFRD (15 men/12 women), age 30.6 ± 11.5 (SD) years, BMI 22.4 ± 4.0 kg/m², were included. Fifteen patients had low BMI (<22 kg/m² for women, <23 kg/m² for men) and 12 patients had at target BMI (≥22 kg/m²for women, ≥BMI 23 kg/m² for men). Patients with low BMI had an increase in their BMI from 19.5 ± 1.7 to 21.4 ± 2.2 kg/m² at one year (p = 0.002), and 21.8 ± 1.8 kg/m² at three years (p = 0.004) after ETI initiation. Four patients (out of 15) in the low BMI group had achieved normal BMI by the end of study follow up. There was no change in weight in the at target BMI group. HbA1c and basal insulin requirements did not change in either group. Five patients started non-insulin therapies.

Conclusion

BMI increased after ETI therapy in CFRD patients with low BMI, but not in those with at target BMI. The use of non-insulin therapies is increasing in CFRD and should be evaluated in future studies.

Background

Post-operative fluid restriction after transsphenoidal surgery (TSS) for pituitary tumors may effectively prevent delayed hyponatremia, the most common cause of readmission. However, implementation of individualized fluid restriction interventions after discharge is often complex and poses challenges for provider and patient. The purpose of this study was to understand the factors necessary for successful implementation of fluid restriction and discharge care protocols following TSS.

Methods

Semi-structured interviews with fifteen patients and four caregivers on fluid discharge protocols were conducted following TSS. Patients and caregivers who had surgery before and after the implementation of updated discharge protocols were interviewed. Data were analyzed inductively using a procedure informed by rapid and thematic analysis.

Results

Most patients and caregivers perceived fluid restriction protocols as acceptable and feasible when indicated. Facilitators to the protocols included clear communication about the purpose of and strategies for fluid restriction, access to the care team, and involvement of patients’ caregivers in care discussions. Barriers included patient confusion about differences in the care plan between teams, physical discomfort of fluid restriction, increased burden of tracking fluids during recovery, and lack of clarity surrounding desmopressin prescriptions.¹

Conclusion

Outpatient fluid restriction protocols are a feasible intervention following pituitary surgery but requires frequent patient communication and education. This evaluation highlights the importance of patient engagement and feedback to effectively develop and implement complex clinical interventions.

Objective

Systematically review evidence on using GLP-1RAs for reducing BEB in BED and BN.

Methods

Comprehensive literature search (PubMed and Google Scholar) conducted for studies evaluating GLP-1Ras for BEB. Extracted data on study characteristics, efficacy, and safety.

Results

Studies show that GLP-1RAs (liraglutide and dulaglutide) reduce BE frequency and comorbidities in addition to favorable psychiatric side effect profile compared to current options. However, large-scale, blinded placebo-controlled trials are lacking.

Conclusion

Early findings suggest promising effects of GLP-1RAs on BEB. However, rigorous clinical trials are needed to firmly establish efficacy, dosing, safety, and comparative effectiveness before considering GLP-1RAs a viable novel approach.

Objective

To explore the nature and extent of possible residual complaints among Dutch hypothyroid patients using thyroid replacement therapy, we initiated a comprehensive study measuring health-related quality of life (QoL), daily functioning, and hypothyroidism-associated symptoms in patients and control persons.

Methods

An online survey measuring thyroid-specific QoL (ThyPRO), daily functioning, and hypothyroidism-associated symptoms (ThySHI) was distributed among treated hypothyroid patients and control individuals. The advertising text was formulated in an open-ended manner. Patients also provided their most recent thyroid blood values and their thyroid medication.

Results

There was a large-sized impairment of QoL (Cohen’s d = 1.04, +93 % ThyPRO score) in hypothyroid patients on thyroid replacement therapy (n = 1195) as compared to controls (n = 236). Daily functioning was significantly reduced i.e., general health (-38 %), problems with vigorous- (+64 %) and moderate activities (+77 %). Almost 80 % of patients reported having complaints despite thyroid medication and in-range thyroid blood values, with 75 % expressing a desire for improved treatment options for hypothyroidism (total n = 1194). Hypothyroid patients experienced 2.8 times more intense hypothyroidism-associated symptoms than controls (n = 865, n = 203 resp). Patients' median reported serum concentrations were: TSH 0.90 mU/L, FT4 17.0 pmol/L, and FT3 2.67 pmol/L, with 52 % having low T3 levels (<3.1 pmol/L). The QoL was not found to be related to age, sex, BMI, menopausal status, stress, serum thyroid parameters, the origin and duration of hypothyroidism, the type of thyroid medication, or the LT4 dose used.

Conclusions

Our study revealed major reductions in quality of life and daily functioning, and nearly three times more intense hypothyroidism-associated symptoms in treated hypothyroid patients as compared to controls, despite treatment and largely in-range serum TSH/FT4 concentrations. The QoL was not associated with serum thyroid parameters. We recommend future research into the origin of persisting complaints and the development of improved treatment modalities for hypothyroidism.

Objective

The objective of this study was to analyze the risk of malignancy and the histopathology of telomerase reverse transcriptase promoter (TERT) mutated cytologically indeterminate thyroid nodules (ITN).

Methods

A PUBMED search of molecularly tested ITN was conducted and data on TERT mutated ITN with histopathology correlation were extracted.

Results

Twenty-six manuscripts (published between 2014 and 2022) reported on 77 TERT mutated ITN. Sixty-five nodules were malignant (84 %), with 16 (25 %) described with high-risk histopathology, 5 (8 %) described as low-risk, and most without any description. Isolated TERT mutations were malignant in 26/30 ITNs (87 %) with 9 (35 %) described as high risk and none described as low risk. TERT + RAS mutated ITNs were malignant in 29/34 ITNs (85 %) with 3 (10 %) described as high risk and 4 (14 %) described as low risk. Finally, all 5 TERT + BRAFV600E mutated nodules were malignant and 3/5 (60 %) were described as high risk.

Conclusion

TERT mutated ITNs have a high risk of malignancy (84 %), and the current data does not show a difference in malignancy rate between isolated TERT mutations and TERT + RAS co-mutated ITNs. When described, TERT + RAS co-mutated ITNs did not have a higher rate of high-risk histopathology as compared to isolated TERT mutated lesions. Most TERT mutated ITNs did not have a description of histopathology risk and the oncologic outcomes, including rate of recurrence, metastases, and disease specific survival, are unknown. Further data is needed to determine if TERT mutated ITNs should be subjected to aggressive initial treatment.

Introduction

The prevalence of fatigue in patients with diabetes mellitus (DM) can be as high as 50 %. Physical, mental, and psychosocial components of fatigue negatively impact quality of life (QOL), morbidity and mortality. Several tools have been developed to address fatigue, but none specifically for measuring fatigue in DM. The aim of this study was to assess the impact of diabetes and neuropathy on fatigue using the Norfolk QOL-Fatigue (QOL-F) survey.

Methods

605 adult participants from [Anonymous] were recruited (400 subjects with type 1 or type 2 DM and 205 subjects without diabetes (controls)). All subjects completed the Norfolk QOL-F. Demographics, weight, BMI, and duration of diabetes were obtained. The Norfolk QOL-F, a 35-item validated questionnaire, assesses five domains: subjective fatigue, physical and cognitive fatigue, reduced activities, impaired activities of daily living, and depression.

Results

Subjects with DM reported significantly higher fatigue total scores (52.63vs33.89, p < 0.0001) and in all five domains when compared to controls. Patients with DM with neuropathy were significantly more fatigued than those without (59.72vs27.83, p < 0.0001). Fatigue scores in patients with DM without neuropathy were similar to controls (27.83vs33.89, p = NS). In multivariate analysis, age, gender, and presence of neuropathy significantly impacted fatigue scores.

Conclusions

The Norfolk QOL-F questionnaire can potentially identify the impact of chronic diseases such as diabetes on fatigue. Assessing the different components of fatigue is important for clinicians in improving disease management and outcomes. Further investigations are needed to confirm these observations in specific cohorts with other comorbidities.

Objective

Peripheral sensory neuropathy (PSN) is a common complication of type 2 diabetes (T2DM) that can lead to frequent ulcerations, lower extremities, and reduced quality of life. Imbalance in the circulating levels of angiogenic growth factors, notably, angiopoietin (Ang)-1, Ang-2 and vascular endothelial growth factor (VEGF) may be among the underlying mechanisms of PSN in T2DM patients. We studied the association between PSN and angiogenic growth factors, Ang-1, Ang-2 and VEGF in T2DM patients in Ghana.

Methods

In a case-control study design, PSN was evaluated in 160 patients with T2DM and 108 nondiabetic controls using vibration perception threshold (VPT) and diabetic neurological examination (DNE). The definition of PSN was abnormal VPT (≥25 mV) or the presence of neuropathic symptoms on examination (DNE score > 3). In addition, fasting venous blood samples were collected to measure circulating levels of Ang-1, Ang-2 and VEGF.

Results

Compared to non-diabetic controls, patients with T2DM had a higher prevalence of PSN using abnormal VPT (20.6 % vs 2.8 %, p < 0.001) or neuropathic symptoms (35.6 % vs 3.7 %, p < 0.001). Compared to nondiabetic controls, patients with T2DM had increased levels of Ang-2 [597 (274 – 1005) vs 838 (473 – 1241) ng/ml, p = 0.018] and VEGF [48.4 (17.4 – 110.1) vs 72.2 (28 – 201.8), p = 0.025] and decreased Ang-1 levels [41.1 (30 – 57.3) vs 36.1 (24.7 – 42.1) ng/ml, p = 0.01]. In regression analyses, an increase in Ang-1 levels was associated with decreased odds, while an increase in Ang-2 levels was associated with increased odds, of abnormal VPT and neuropathic symptoms in T2DM patients.

Conclusion

In our study population, PSN was associated with reduced plasma levels of Ang-1 and increased plasma levels of Ang-2 in patients with T2DM. Therefore, an imbalance of angiopoietins may be associated with PSN in T2DM.