Journal of Clinical and Translational Endocrinology最新文献

Background

Overt hypothyroidism leads to increased cardiovascular risk, primarily through effects the disorder has on lipids. Most studies investigating lipids in the setting of hypothyroidism, have been performed in predominantly Caucasians in North America and Europe. Different patterns and prevalence of dyslipidemia have been described; one study reporting dyslipidemia in 90% of patients with hypothyroidism. The prevalence of dyslipidemia in overt hypothyroidism among the ethnically diverse predominantly black South African population is unknown.

Methodology

A retrospective case-control study evaluating lipid profiles of an ethnically diverse cohort of patients with overt hypothyroidism (TSH > 10 mIU/L) attending two academic hospitals in Johannesburg, South Africa from September 2006–September 2016. Patients with primary or secondary causes for dyslipidemia and those taking lipid-lowering therapy were excluded.

Results

Two hundred and six patients with hypothyroidism were included and compared to 412 euthyroid controls matched for sex, ethnicity, and age. Most hypothyroid patients were female (n = 180;67.5 %). Median TSH was similar across all ethnic groups (p = 0.09). Median TC, TG and LDL-C were higher in hypothyroid patients (p < 0.01). Normal lipid profiles were found in 29.44 % of all hypothyroid patients. However, a greater proportion, 47 of 124 (37.90 %), black African patients with hypothyroidism had a normal lipid profile.

Conclusion

Dyslipidemia is less common in black African patients with hypothyroidism. This is probably due to this population group being in an earlier stage of epidemiologic transition. Those with hypothyroidism were at greater overall cardiovascular risk based on TC/HDL-C ratio but did not reach high risk atherogenic profiles reported in previous studies.

This study aimed to analyze clinical practices concerning cystic fibrosis-related diabetes (CFRD) screening in France. A web-based questionnaire was distributed between December 1, 2020 and January 31, 2021 among 47 cystic fibrosis centers including pediatric, adult, and mixed units. In accordance with guidelines, 92.8% of CF centers performed annual oral glucose tolerance tests (OGTT). Overall, 86.3% of CF centers performed 1- and 2-hour blood glucose determinations following OGTT. The OGTT was conducted before 10 years of age in 73% of pediatric centers. Continuous glucose monitoring (CGM) and laboratory glycated hemoglobin were employed for CFRD screening in 86.5% and 50% of centers, respectively. CGM was carried out in 69% of centers after glucose tolerance abnormalities had been detected in OGTT. Most CF centers used OGTT and CGM for CFRD screening. Studies are required to assess CGM usefulness as a validated tool in CFRD screening.

In obesity, the hormonal secretion of the thyroid gland switches from homeostasis to type 2 allostasis in order to adapt to persistent modifications of adipose tissue and inflammation. Previous meta-analyses have linked obesity with an increased risk of developing thyroid diseases, prediabetes, and type 2 diabetes mellitus. We designed an observational cross-sectional study including all female patients presenting consecutively in an ambulatory clinic for 16 months. This study aimed to describe the level of serum cytokines and chemokines in relation to TSH, fT4 and insulin resistance (IR) indexes in patients with subclinical hypothyroidism (SCH). The study included 72 women with a median age of 59 ± 17.75 years, and a mean BMI (Body Mass Index) of 31.48 ± 6.75 kg/m². Modelling homeostasis model assessment of IR indices (HOMA-IR) based on chemokines (IL-8, CXCL10, CXCL11, leptin), C-reactive protein, the presence or absence of SCH, taking into account age, BMI, abdominal circumference, glycated haemoglobin (HbA1c), and anti-thyroid peroxidase antibodies (ATPO) as covariates, identified a single chemokine that was significantly associated with the dependent variable (IL-8). IR indices are negatively associated with IL-8 in female patients with subclinical hypothyroidism, but the effect of the cytokine is minimal. BMI rather than TSH influences the level of CXCL11 in our population. CXCL10 has a tendency to increase in patients with SCH, obesity and prediabetes, with no association with TSH.

Background

Diabetes and liver disease are life-threatening complications of cystic fibrosis (CF). CF-liver disease is a risk factor for CF related diabetes (CFRD) development, but the underlying mechanisms linking the two co-morbidities are not known. The objective of this pilot study was to characterize glucose metabolism in youth with CF with and without liver disease.

Methods

In this two-center cross-sectional study, 20 youth with CF with and without liver disease underwent a 3-hour oral glucose tolerance test. Subjects were categorized by liver disease (LD) status [no LD, mild LD, severe LD] and diabetes status. Measures of glucose excursion, islet cell secretory responses, insulin sensitivity and clearance were obtained.

Results

Participants with severe LD had the highest fasting, peak, and glucose area under the curve over 3 h (AUC_3h) among individuals with CFRD (interaction p < 0.05). In parallel with glycemic changes, prandial β-cell secretory response (AUC _{C-peptide 3h}) was lower in those with severe LD compared to mild or no LD (p < 0.01). There was a trend of higher HOMA-IR in those with severe LD (p = 0.1) as well as lower fasting insulin clearance in those with mild and severe LD compared to no LD (p = 0.06) and lower prandial insulin clearance in severe LD among those with CFRD (interaction p = 0.1).

Conclusion

In this small cohort, subjects with severe LD tended to have more impaired glycemia, insulin secretion, insulin sensitivity and clearance. Larger studies are imperative to define the pathogenesis to inform clinical care guidelines in terms of CFRD screening, diagnosis, and treatment options.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for coronavirus disease 2019 (COVID-19) has been a major cause of morbidity and mortality globally. Older age, and the presence of certain components of metabolic syndrome, including hypertension have been associated with increased risk for severe disease and death in COVID-19 patients. The role of antihypertensive agents in the pathogenesis of COVID-19 has been extensively studied since the onset of the pandemic. This review discusses the potential pathophysiologic interactions between hypertension and COVID-19 and provides an up-to-date information on the implications of newly emerging SARS-CoV-2 variants, and vaccines on patients with hypertension.

The association of estrogen supplementation use and quality of life in women with cystic fibrosis (CF) is not well characterized. In this cross-sectional study, women with CF completed quality of life questionnaires during a routine CF clinic visit. The use of estrogen supplementation was associated with higher quality of life scores in all domains of the CF questionnaire-revised (CFQ-R) and was significant in the role limitations and respiratory domains. Most participants who were not currently using estrogen supplementation had previously used estrogen supplementation. Most participants had used estrogen to regulate menses, prevent pregnancy and control symptoms around menses. Use of estrogen supplementation was not associated with differences in life-space mobility or screening for sexual dysfunction. This is the largest study to date investigating the association of estrogen supplementation and quality of life in women with CF. Prospective randomized studies are needed to clarify the association of estrogen supplementation and quality of life in women with CF.

The development and introduction of modulator therapies have completely shifted the paradigm for the treatment of cystic fibrosis (CF). Highly effective modulator therapies have driven marked improvements in lung function, exacerbation rate, weight and quality of life in CF patients. However, their effect on CF related diabetes (CFRD) is not well delineated. The role of CF transmembrane conductance regulator (CFTR) in CFRD pathogenesis is inadequately understood and research aimed at deciphering the underlying mechanisms of CFRD continues to evolve. In this review, we summarize what is known regarding the effect of CFTR modulators on CFRD. Small studies using ivacaftor monotherapy in gating mutations have revealed improvement in insulin secretion, glucose tolerance and/or decrease in insulin requirement. However, lumacaftor/ivacaftor studies (primarily in delta F 508 homozygous) have not revealed significant improvement in CFRD or glucose tolerance. No studies are yet available regarding the effect of the highly effective triple therapy (elexacaftor/tezacaftor/ivacaftor) on CFRD or insulin secretion. CFTR modulators might affect development or progression of CFRD through many mechanisms including improving insulin secretion by correcting the CFTR defect directly, improving ductal function, reducing islet inflammation, and improving incretin secretion or by enhancing insulin sensitivity via reduced systemic inflammation and increased physical activity driven by improved lung function and quality of life. On the other hand, they can stimulate appetite and improve gastrointestinal function resulting in increased caloric intake and absorption, driving excessive weight gain and potentially increased insulin resistance. If the defect in insulin secretion is reversible then it is possible that initiation of CFTR modulators at a younger age might help prevent CFRD. Despite the advances in CF management, CFRD remains a challenge and knowledge continues to evolve. Future studies will drive better understanding of the role of highly effective CFTR modulators in CFRD.

Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in patients with cystic fibrosis (CF). Prevalence of CFRD increases with age and is greater with severe mutations. Other risk factors associated with CFRD are female sex, pancreatic insufficiency, liver disease, need for gastrostomy tube feedings, history of bronchopulmonary aspergillosis, and poor pulmonary function. CFRD is related to worse clinical outcomes and increased mortality. Early diagnosis and treatment have been shown to improve clinical outcomes. Screening for CFRD is recommended with an annual oral glucose tolerance test (OGTT) starting at age 10 years. Diagnosis of CFRD is made by standard American Diabetes Association (ADA) criteria during baseline health. CFRD can also be diagnosed in individuals with CF during acute illness, while on enteral feeds, and after transplant. In this review we will discuss the epidemiology of CFRD and provide an overview of the advantages and pitfalls of current screening and diagnostic tests for CFRD.