Zonulin as a potential putative biomarker of risk for shared type 1 diabetes and celiac disease autoimmunity.

The incidence of type 1 diabetes (T1D) is increasing annually, in addition to other childhood-onset autoimmune diseases. This review is inspired by recent strides in research defining the pathophysiology of autoimmunity in celiac disease, a disease that has significant genetic overlap with T1D. Population genetic studies have demonstrated an increased proportion of newly diagnosed young children with T1D also have a higher genetic risk of celiac disease, suggesting that shared environmental risk factors are driving the incidence of both diseases. The small intestine barrier forms a tightly regulated interface of the immune system with the outside world and largely controls the mucosal immune response to non-self-antigens, dictating the balance between tolerance and immune response. Zonulin is the only known physiological modulator of the intercellular tight junctions, important in antigen trafficking, and therefore, is a key player in regulation of the mucosal immune response. While usually tightly controlled, when the zonulin pathway is dysregulated by changes in microbiome composition and function, antigen trafficking control is lost, leading to loss of mucosal tolerance in genetically susceptible individuals. The tenant of this hypothesis is that loss of tolerance would not occur if the zonulin-dependent intestinal barrier function is restored, thereby preventing the influence of environmental triggers in individuals genetically susceptible to autoimmunity. This review outlines the current research and a structured hypothesis on how a dysregulated small intestinal epithelial barrier, a "leaky gut," may be important in the pathogenesis of autoimmunity in certain individuals at risk of both T1D and celiac disease.

Low Risk of Adrenal Insufficiency After Use of Low- to Moderate-Potency Topical Corticosteroids for Children With Atopic Dermatitis.

Our objective was to assess the risk of adrenal insufficiency (AI) with short-term use of low- to moderate-potency topical corticosteroids (TCS) for treatment of atopic dermatitis. Our systematic literature search revealed 9 studies (n = 371) that evaluated AI using adrenocorticotropic hormone stimulation testing, with measures of serum cortisol levels at baseline and following at least 2 weeks of TCS application. Biochemical AI was defined by a stimulated cortisol level of ≤18.0 µg/dL (~500 nmol/L). The overall proportion of AI with low-to-moderate TCS use was 2.7% (95% confidence interval = 1.47% to 4.89%). None of the children showed any clinical evidence of AI or adrenal crisis. Short-term use of low- to moderate-potency TCS for the treatment of atopic dermatitis is associated with a low risk of adrenal suppression. General practitioners do not need to test these patients for adrenal suppression in the absence of concerning signs and symptoms of AI.

Dyslipidaemia and statin use in individuals aged 10 to <40 years in the T1D Exchange clinic registry.

For individuals aged 10 to <40 years with type 1 diabetes and dyslipidaemia, US national guidelines recommend consideration of statin therapy based on age, low-density lipoprotein cholesterol (LDL-C) level and other cardiovascular risk factors. We evaluated dyslipidaemia prevalence, statin therapy use, and associations between not meeting target LDL-C [<100 mg/dL (<5.55 mmol/L)] and other cardiovascular disease (CVD) risk factors in individuals aged 10 to <40 years in the T1D Exchange clinic registry. In 7223 participants, statin use was 2% in 10 to <18 year olds, 4% in 18 to <25 year olds, and 21% in 25 to <40 year olds. Individuals not on statin therapy with LDL-C above target were more likely to have ≥1 additional CVD risk factor(s) than those with LDL-C in the target range for all age groups (all P < 0.01). While most individuals not on statin therapy had LDL-C in the target range, those who did not were more likely to have ≥1 additional CVD risk factor(s), and therefore longitudinal study of lipid levels and statin use is needed to see if treatment of dyslipidaemia to target LDL-C levels may lower the risk of future CVD in individuals aged 10 to <40 years with type 1 diabetes.

Evaluation of Hypothalamic-Pituitary-Adrenal Axis Suppression following Cutaneous Use of Topical Corticosteroids in Children: A Meta-Analysis.

BACKGROUND/AIMS: A meta-analysis was performed to determine the likelihood of hypothalamic-pituitary-adrenal (HPA) axis suppression following short-term cutaneous treatment of atopic dermatitis with topical corticosteroids (TCS) in pediatric patients. METHODS: All published pediatric clinical trials evaluating TCS use with pre- and post-treatment HPA axis assessment by cosyntropin stimulation testing were included. RESULTS: Of 128 eligible trials, 12 were selected for meta-analysis with a total of 522 participants. There were 20 observed cases of HPA axis suppression (3.8%, 95% CI 2.4-5.8). The percentage of HPA axis suppression with low- (classes 6-7), medium- (classes 3-5) and high-potency (classes 1-2) TCS use was 2% (3 of 148 patients, 95% CI 0.7-5.8), 3.1% (7 of 223 patients, 95% CI 1.5-6.3), and 6.6% (10 of 151 patients, 95% CI 3.6-11.8), respectively. CONCLUSION: There is a low rate of reversible HPA axis suppression with the use of mid- to low-potency TCS compared to more potent formulations. In pediatric clinical practice, the limited use of mid- to low-potency TCS is rarely associated with clinically significant adrenal insufficiency or adrenal crisis. In the absence of signs and symptoms of adrenal insufficiency, there is little need to test the HPA axis of these patients.