An update on methods for assessing bone quality and health in Cystic fibrosis.

With increasing life expectancy in people with Cystic fibrosis (CF), the focus of clinical care has shifted to management and prevention of non-pulmonary comorbidities. CF related bone disease, defined by low bone mineral density (BMD), is prevalent across all age groups and acknowledges the increased fractures rates that negatively impact lung function and quality of life. Dual energy X-ray absorptiometry (DXA) measurement of bone mineral content (BMC) and "areal" BMD (aBMD) is recommended for identifying and monitoring bone health in children and adults due to its low cost, low radiation exposure, and widespread availability. Recent studies in children and adolescents with chronic illness focus on adjustment of BMC and aBMD measurements for height due to the effects of short stature and delayed maturation on bone size. Expanded reference databases for alternate imaging sites such as the ultradistal radius and hip present opportunities for research and long-term monitoring. As the two-dimensional nature of DXA imposes limitations, we highlight other imaging modalities including peripheral quantitative computed tomography QCT (pQCT), magnetic resonance imaging, and quantitative ultrasound (QUS). These tools, while primarily used in a research setting, can impart information on true volumetric bone density and bone microarchitecture as well as contribute to fracture assessment and prediction. Due to the high morbidity and mortality associated with vertebral and hip fracture, we will present on vertebral fracture assessment (VFA) in both children and adults as well as applied analyses including hip structural analysis (HSA), trabecular bone score (TBS), and fracture risk assessment (FRAX) for high risk groups. Questions remain on the future clinical applicability and accessibility of these assessment and prediction tools, longitudinal monitoring through adolescence and adulthood, and how outcome measures may guide bone modifying therapies.

Eating disorders and body image in cystic fibrosis.

Eating disorders and disturbed body image have been reported in individuals with cystic fibrosis (CF) and may contribute to poor weight gain, reduced lung function and increased mortality. CF individuals often look and feel different from their peers and bear the additional burden of body-altering side effects of treatment. As a result, the impact of disorders such as binge eating, anorexia nervosa, and bulimia nervosa may adversely affect the social, emotional, and physical development of those with CF. Multiple risk factors may contribute to the development of an eating disorder in CF. Growth failure is affected by the physical impairments of CF, including pancreatic insufficiency, high energy demands, respiratory infections, and delayed and stunted growth and puberty. Psychological factors, such as CF associated depression and anxiety, intense focus on BMI, lack of control in a chronic disease, and preoccupation with morbidity and mortality, likely further contribute. Exercise inefficiency, secondary to poor lung function, low BMI and pulmonary exacerbations, and the potential for medication manipulation are also additional risk factors. The intense scrutiny around BMI may lead to a poor relationship with food, including disordered eating habits, abnormal mealtime behaviors, and stressful caregiver-patient interactions regarding meals. This further contributes to a discrepancy between ideal CF nutritional standards and the reality of the challenges of appropriate daily energy intake for an individual with CF. It is imperative that CF providers are equipped to identify potential eating disorders and disturbed body image in their CF patients. Improved screening and monitoring practices should be developed and implemented, with multidisciplinary support from all CF care team members, including dietitians, mental health professionals, and social workers, to best support holistic care and optimize outcomes. Increased attention to these concerns may help reduce CF related morbidity and mortality.

COVID-19: Pathophysiology and implications for cystic fibrosis, diabetes and cystic fibrosis-related diabetes.

The novel SARS-CoV-2 coronavirus (COVID-19) has become a global health crisis since its initial outbreak in Wuhan, China in December 2019. On January 30, 2020, the WHO recognized the COVID-19 outbreak as a Public Health Emergency, and on March 11, 2020, it was declared a pandemic. Although all age groups have been affected, patients with cystic fibrosis (CF) and patients with type 1 or type 2 diabeteshave been categorized as highly vulnerable to SARS-CoV-2 infection. Thus far, studies have found that the incidence of SARS-CoV-2 in the CF population is lower than the general population. We review the underlying protective mechanisms which may reduce inflammation and lung damage in CF patients, thus decreasing their risk of severe COVID-19. While the effect of SARS-CoV-2 in those with diabetes related to CF is unknown, other forms of diabetes have been associated with more severe disease. To further understand the potential impact of SARS-CoV-2 in cystic fibrosis-related diabetes, we provide a comprehensive overview of the potential factors contributing to COVID-19 severity in other forms of diabetes, including direct viral effect on the pancreas and indirect effects related to hyperglycemia and immune dysregulation.

A Clinician's guide to vitamin D supplementation for patients with cystic fibrosis.

Vitamin D deficiency is common in the general population, and even more so in patients with cystic fibrosis. Deficiency is exacerbated in cystic fibrosis patients because of a myriad of causes including malabsorption, decreased fat mass, reduced 25-hydroxylation of vitamin D, reduced exposure to sunlight, decreased vitamin D binding protein, and exposure to drugs that increase catabolism. In turn, vitamin D deficiency can contribute to poor bone health. Additionally, it may contribute to pulmonary decline in the form of worsening pulmonary function, increased colonization with pathogens, and increased pulmonary exacerbation. Because vitamin D deficiency is correlated with negative clinical effects in multiple organ systems of patients with cystic fibrosis, it is important to screen for and treat deficiency in these patients. The Cystic Fibrosis Foundation has issued guidelines for the treatment of vitamin D deficiency, targeting serum levels of 25-hydroxyvitamin D of at least 30 ng/ml. The guidelines offer age-specific escalating dose regimens depending on serum vitamin D levels, with monitoring at 12- week intervals after changing therapy. They address the literature on alternative vitamin D sources, such as UV lamps, ideal formulations (cholecalciferol in preference to ergocalciferol), and optimal vehicles of administration. Despite these detailed recommendations, most centers are still unable to achieve in-target serum vitamin D levels for many of their patients. Future research examining ideal treatment regimens to achieve serum targets and maximize clinical effects are needed. Moreover, it is unknown whether vitamin D sufficiency will be easier to achieve on new triple therapy cystic fibrosis drug combinations, and how these drugs will contribute to vitamin D-related clinical outcomes.

Association between attendance at an American diabetes camp and improvements in glycaemic control and treatment satisfaction.

INTRODUCTION: Few studies have evaluated glycaemic control using continuous glucose monitoring (CGM) in individuals before and after attendance at a diabetes camp or by comparing control groups at home to control groups at camp. METHODS: Youth (6-17 years) with T1D and receiving insulin therapy were enrolled at a week-long diabetes camp. They participated in three clinic visits: at the start of a week at home, by initiating a Dexcom G6 CGM system; at the start of a week at camp, where the home week G6 was removed and a camp week G6 was inserted; and after camp, where the camp week G6 was removed. We administered Problem Areas in Diabetes (PAID) surveys at the second and third visits. Participants with <80% CGM data coverage or who did not complete all PAID surveys were excluded from analysis. We compared glycaemic control and PAID scores between the week at home and week at camp. RESULTS: Of 76 enrolled campers, 69 completed the study and 52 had results that qualified for analysis. The mean participant age was 12.5 ± 2.2 years. Camp was associated with significantly improved treatment satisfaction, time in desired glucose range and insulin sensitivity. Time in hyperglycaemia and basal insulin requirements decreased significantly. CONCLUSIONS: Diabetes camp is associated with significant improvements in diabetes treatment satisfaction and glycaemic control compared to home care.

Automatic referrals within a cystic fibrosis multidisciplinary clinic improve patient evaluation and management.

AUTOMATIC REFERRALS WITHIN A CYSTIC FIBROSIS MULTIDISCIPLINARY CLINIC IMPROVE PATIENT EVALUATION AND MANAGEMENT. BACKGROUND: Cystic fibrosis (CF) affects multiple systems beyond the pulmonary system, including the gastrointestinal and endocrine systems. Many CF clinics focus on pulmonary effects, initiating referrals to other specialties only when a condition has been identified by the primary pulmonary team. Unfortunately, many extrapulmonary manifestations of cystic fibrosis may be overlooked. Thus, implementing a multidisciplinary clinic with automatic referrals to designated subspecialists may improve patient care. METHODS: This retrospective review of medical records examined the effects of integrating a pediatric endocrinologist into the University of Massachusetts Memorial Medical Center Pediatric CF Clinic in March 2017. In this new CF/Endocrinology clinic, all patients scheduled to see a pulmonologist were automatically referred to pediatric endocrinology. We compared rates of referrals to pediatric endocrinology, oral glucose tolerance tests (OGTTs), and bone density (DEXA) scans before (2013-2016) and after (2017-2020) implementation of this clinic. We also recorded endocrine disorders being evaluated and/or treated after implementation. RESULTS: The rate of referral to pediatric endocrinology increased from before (4%) to after (82%) (p < 0.0001) implementation of the CF/Endocrinology Clinic. OGTT and DEXA scan screening rates also increased from 7% to 65% (p < 0.0001) and from 6% to 63% (p = 0.0011), respectively. Before implementation, patients were evaluated by endocrinology primarily for CF-related diabetes. After implementation, the diversity of endocrine conditions under evaluation and/or management increased substantially; the most common were vitamin D insufficiency/deficiency (37.2% of clinic patients), glycemic dysregulation (36.8%), and poor weight gain/failure to thrive (17.5%). CONCLUSION: Implementing a multidisciplinary CF clinic with automatic referrals to pediatric endocrinology improves patient care by promoting early detection and management of endocrine concerns that may have been overlooked and by increasing OGTT and DEXA screening rates.

Use of hemoglobin A1c to identify dysglycemia in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) leads to pancreatic endocrine dysfunction with progressive glycemic disturbance. Approximately 30%-50% of people with CF eventually develop CF-related diabetes (CFRD). Pre-CFRD states progress from indeterminant glycemia (INDET) to impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Screening guidelines recommend inconvenient annual 2-hour oral glucose tolerance tests (OGTTs), beginning at age 10 years. More efficient methods, such as hemoglobin A1C (HbA1c), have been evaluated, but only limited, relatively small studies have evaluated the association between HbA1c and pre-CFRD dysglycemic states. OBJECTIVE: To determine whether HbA1c is an appropriate screening tool for identifying patients with pre-CFRD dysglycemia to minimize the burden of annual OGTTs. METHODS: This retrospective review evaluated medical records data of all University of Massachusetts Memorial Health System CF patients with an HbA1c result within 90 days of an OGTT between 1997 and 2019. Exclusion criteria were uncertain CF diagnosis, other forms of diabetes, or incomplete OGTT. In total, 56 patients were included and categorized according to OGTT results (American Diabetes Association criteria): normal glucose tolerance, INDET, IFG, or IGT. Associations were evaluated between HbA1c and OGTT results and between HbA1c and pre-CFRD dysglycemic states. RESULTS: Mean HbA1c was not significantly different between patients with normal glucose tolerance and those in the INDET (p = 0.987), IFG (p = 0.690), and IGT (p = 0.874) groups. Analysis of variance confirmed the lack of association between HbA1c and glycemia, as mean HbA1c was not significantly different amongst the four categories (p = 0.250). CONCLUSION: There is increasing awareness of the impact of pre-CFRD states, including reduced pulmonary function and nutritional status. Unfortunately, our results do not support using HbA1c as a screening tool for pre-CFRD dysglycemia, specifically INDET, IFG, and IGT. Further studies are warranted to evaluate more efficient screening methods to reduce the burden of annual OGTTs.

Sleep and eating behavior in adults at risk for type 2 diabetes.

Insufficient quantity and quality of sleep may modulate eating behavior, everyday physical activity, overall energy balance, and individual risk of obesity and type 2 diabetes. We examined the association of habitual sleep quantity and quality with the self-reported pattern of eating behavior in 53 healthy urban adults with parental history of type 2 diabetes (30 F/23 M; mean (s.d.) age: 27 (4) years; BMI: 23.9 (2.3) kg/m(2)) while taking into consideration the amount of their everyday physical activity. Participants completed 13 (3) days of sleep and physical activity monitoring by wrist actigraphy and waist accelerometry while following their usual lifestyle at home. Overnight laboratory polysomnography was used to screen for sleep disorders. Subjective sleep quality was measured with the Pittsburgh Sleep Quality Index. Eating behavior was assessed using the original 51-item and the revised 18-item version of the Three-Factor Eating Questionnaire including measures of cognitive restraint, disinhibition, hunger, and uncontrolled and emotional eating. In multivariable regression analyses adjusted for age, BMI, gender, race/ethnicity, level of education, habitual sleep time measured by wrist actigraphy and physical activity measured by waist accelerometry, lower subjective sleep quality was associated with increased hunger, more disinhibited, uncontrolled and emotional eating, and higher cognitive restraint. There was no significant association between the amount of sleep measured by wrist actigraphy and any of these eating behavior factors. Our findings indicate that small decrements in self-reported sleep quality can be a sensitive indicator for the presence of potentially problematic eating patterns in healthy urban adults with familial risk for type 2 diabetes.

Reduced physical activity in adults at risk for type 2 diabetes who curtail their sleep.

Adults with parental history of type 2 diabetes have high metabolic morbidity, which is exacerbated by physical inactivity. Self-reported sleep <6 h/day is associated with increased incidence of obesity and diabetes, which may be mediated in part by sleep-loss-related reduction in physical activity. We examined the relationship between habitual sleep curtailment and physical activity in adults with parental history of type 2 diabetes. Forty-eight young urban adults with parental history of type 2 diabetes (27 F/21 M; mean (s.d.) age 26 (4) years; BMI 23.8 (2.5) kg/m(2)) each completed 13 (2) days of sleep and physical activity monitoring by wrist actigraphy and waist accelerometry while following their usual lifestyle at home. Laboratory polysomnography was used to screen for sleep disorders. The primary outcome of the study was the comparison of total daily activity counts between participants with habitual sleep <6 vs. ≥6 h/night. Secondary measures included daily time spent sedentary and in light, moderate, and vigorous physical activity. Short sleepers had no sleep abnormalities and showed signs of increased sleep pressure consistent with a behavioral pattern of habitual sleep curtailment. Compared to participants who slept ≥6 h/night, short sleepers had 27% fewer daily activity counts (P = 0.042), spent less time in moderate-plus-vigorous physical activity (-43 min/day; P = 0.010), and remained more sedentary (+69 min/day; P = 0.026). Our results indicate that young urban adults with parental history of type 2 diabetes who habitually curtail their sleep have less daily physical activity and more sedentary living, which may enhance their metabolic risk.

Changes in insulin secretion and action in adults with familial risk for type 2 diabetes who curtail their sleep.

OBJECTIVE: Experimental sleep deprivation is accompanied by changes in glucose regulation. However, the effects of chronic sleep insufficiency on insulin secretion and action in populations at high risk for type 2 diabetes are not known. This study examined the relationship between objectively documented habitual sleep curtailment and measures of insulin sensitivity, insulin secretion, and oral glucose tolerance in free-living adults with parental history of type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 47 healthy participants with parental history of type 2 diabetes (26 female/21 male, mean [SD] age 26 [4] years and BMI 23.8 [2.5] kg/m(2)) completed 13 (SD = 2) days of sleep and physical activity monitoring by wrist actigraphy and waist accelerometry while following their usual lifestyle at home. Laboratory polysomnography was used to screen for sleep disorders. Indices of diabetes risk based on oral glucose tolerance tests were compared between participants with habitual short sleep and those with usual sleep duration >6 h/day. RESULTS: Consistent with a behavioral pattern of habitual sleep curtailment, short sleepers obtained an average of 1.5 h less sleep per night and showed signs of increased sleep pressure. Participants who habitually curtailed their sleep had considerably higher indices of insulin resistance and increased insulin secretion but maintained normal glucose tolerance similar to that of subjects who slept more. CONCLUSIONS: Young lean adults with parental history of type 2 diabetes who habitually curtail their sleep have increased insulin resistance and compensatory hyperinsulinemia--a pattern that has been associated with higher risk of developing diabetes in such susceptible individuals.

Power-up: a collaborative after-school program to prevent obesity in African American children.

BACKGROUND: Schools represent a key potential venue for addressing childhood obesity. OBJECTIVE: To assess the feasibility of Power-Up, an after-school program to decrease obesity risk among African American children, using community-based participatory research (CBPR) principles. METHODS: Teachers led 14 weekly nutrition and physical activity sessions during afterschool care at the Woodlawn Community School on Chicago's South Side. Forty African American children ages 5 to 12 participated; their 28 parents discussed similar topics weekly at pickup time, and families practiced relevant skills at home. Pre- and post-intervention anthropometrics, blood pressure, dietary measures, and health knowledge and beliefs for children and parents were compared in univariate analysis. RESULTS: At baseline, 26% of children were overweight; 28% were obese. Post-intervention, mean body mass index (BMI) z scores decreased from 1.05 to 0.81 (p<.0001). Changes were more pronounced for overweight (-0.206 z-score units) than for obese children (-0.062 z-score units; p=.01). Girls decreased their combined prevalence of overweight/obesity from 52% to 46%; prevalence across these categories did not change for boys. The prevalence of healthful attitudes rose, including plans to "eat more foods that are good for you" (77% to 90%; p=.027) and "planning to try some new sports" (80% to 88%; p=.007). CONCLUSION: Children in the Power-Up program reduced mean BMI z scores significantly. The after-school venue proved feasible. The use of CBPR principles helped to integrate Power-Up into school activities and contributed to likelihood of sustainability. Engaging parents effectively in the afterschool time frame proved challenging; additional strategies to engage parents are under development. Plans are underway to evaluate this intervention through a randomized study.