People with cystic fibrosis (CF) are at risk for dysglycaemia caused by progressive beta cell dysfunction and destruction due to pancreatic exocrine disease and fibrosis. CF-related diabetes (CFRD) ...is a unique form of diabetes that has distinctive features from both type 1 and type 2 diabetes. Recent advances in diabetes technology may be of particular benefit in this population given the complex, multi-system organ involvement and challenging health issues that people with CFRD often face. This review summarises how diabetes technologies, such as continuous glucose monitors (CGMs) and insulin delivery devices: (1) have improved our understanding of CFRD, including how hyperglycaemia affects clinical outcomes in people with CF; (2) may be helpful in the screening and diagnosis of CFRD; and (3) offer promise for improving the management of CFRD and easing the burden that this diagnosis can add to an already medically complicated patient population.People with cystic fibrosis (CF) are at risk for dysglycaemia caused by progressive beta cell dysfunction and destruction due to pancreatic exocrine disease and fibrosis. CF-related diabetes (CFRD) is a unique form of diabetes that has distinctive features from both type 1 and type 2 diabetes. Recent advances in diabetes technology may be of particular benefit in this population given the complex, multi-system organ involvement and challenging health issues that people with CFRD often face. This review summarises how diabetes technologies, such as continuous glucose monitors (CGMs) and insulin delivery devices: (1) have improved our understanding of CFRD, including how hyperglycaemia affects clinical outcomes in people with CF; (2) may be helpful in the screening and diagnosis of CFRD; and (3) offer promise for improving the management of CFRD and easing the burden that this diagnosis can add to an already medically complicated patient population.
Diabetes and obesity are highly prevalent among hospitalized patients with coronavirus disease 2019 (COVID-19), but little is known about their contributions to early COVID-19 outcomes. We tested the ...hypothesis that diabetes is a risk factor for poor early outcomes, after adjustment for obesity, among a cohort of patients hospitalized with COVID-19.
We used data from the Massachusetts General Hospital (MGH) COVID-19 Data Registry of patients hospitalized with COVID-19 between 11 March 2020 and 30 April 2020. Primary outcomes were admission to the intensive care unit (ICU), need for mechanical ventilation, and death within 14 days of presentation to care. Logistic regression models were adjusted for demographic characteristics, obesity, and relevant comorbidities.
Among 450 patients, 178 (39.6%) had diabetes-mostly type 2 diabetes. Among patients with diabetes versus patients without diabetes, a higher proportion was admitted to the ICU (42.1% vs. 29.8%, respectively,
= 0.007), required mechanical ventilation (37.1% vs. 23.2%,
= 0.001), and died (15.9% vs. 7.9%,
= 0.009). In multivariable logistic regression models, diabetes was associated with greater odds of ICU admission (odds ratio 1.59 95% CI 1.01-2.52), mechanical ventilation (1.97 1.21-3.20), and death (2.02 1.01-4.03) at 14 days. Obesity was associated with greater odds of ICU admission (2.16 1.20-3.88) and mechanical ventilation (2.13 1.14-4.00) but not with death.
Among hospitalized patients with COVID-19, diabetes was associated with poor early outcomes, after adjustment for obesity. These findings can help inform patient-centered care decision making for people with diabetes at risk for COVID-19.
Bone disease is a frequent complication in adolescents and adults with cystic fibrosis (CF). Early detection and monitoring of bone mineral density and multidisciplinary preventive care are necessary ...from childhood through adolescence to minimize CF-related bone disease (CFBD) in adult CF patients. Approaches to optimizing bone health include ensuring adequate nutrition, particularly intake of calcium and vitamins D and K, addressing other secondary causes of low bone density such as hypogonadism, encouraging weight bearing exercise, and avoiding bone toxic medications. Of the currently available anti-resorptive or anabolic osteoporosis medications, only bisphosphonates have been studied in individuals with CF. Future studies are needed to better understand the optimal approach for managing CFBD.
•Optimizing bone health includes adequate nutrition, intake of calcium and vitamins D and K, and weight bearing exercise.•Bone density should be monitored regularly in patients with CF.•The decision to start pharmacologic therapy and choice of medication should be made on a case-by-case basis.•Only bisphosphonates have been studied specifically in patients with CF.•CFTR modulators offer promise for improving CF bone disease by enhancing overall targeting CFTR dysfunction in bone cells.
Cystic fibrosis-related diabetes (CFRD) is associated with pulmonary decline, compromised nutritional status, and earlier mortality. Although diabetes technology is increasingly being used in ...individuals with CFRD, there is a paucity of data investigating the impact of hybrid closed loop (HCL) technology on glycemia in this patient population.
In this multicenter retrospective study of 13 adults and adolescents with CFRD, 14 days of continuous glucose monitor data were analyzed at baseline, 1 and 3 months after transition to the Tandem t:slim X2 pump with Control IQ™ technology, a HCL system.
Control IQ initiation was associated with a significant increase in % time in target range (70-180 mg/dL), as well as decreases in average glucose, % time in hyperglycemic ranges (% time >180 mg/dL, % time >250 mg/dL), and glycemic variability (standard deviation, coefficient of variation). There was no significant change in % time in hypoglycemia ranges (% time <54 mg/dL, % time <70 mg/dL).
To our knowledge, this is the first study to report a beneficial effect of Food and Drug Administration (FDA)-approved HCL technology on glycemia in adults and adolescents with CFRD to date. Future studies are needed to understand the potential long-term glycemic benefits of HCL devices and to explore the impact of this technology on heath-related quality of life, pulmonary function, nutritional status, and mortality.
Cystic fibrosis related diabetes (CFRD) is associated with pulmonary decline and compromised nutritional status. Emerging data suggest that CFTR dysfunction may play a direct role in the pathogenesis ...of CFRD; however, studies investigating the effect of CFTR modulators on glycemic outcomes in patients with cystic fibrosis (CF) have shown mixed results. The impact of elexacaftor-tezacaftor-ivacaftor (ETI) on glycemic control is currently unknown. Our objective was to investigate the effect of ETI initiation on glycemia in adults with CF using continuous glucose monitoring (CGM).
In this prospective observational study, 34 adults with CF and at least one F508del CFTR mutation wore CGM sensors for 14 days prior to starting ETI and again 3-12 months after ETI initiation. Hypoglycemia symptoms were queried at each visit, and most recent anthropometric measures and spirometry data were obtained by chart review.
Twenty-three participants completed the study. Compared to baseline, average glucose (AG), standard deviation (SD), % time >200 mg/dL, and peak sensor glucose decreased with ETI treatment, and % time in target range 70-180 mg/dL increased. Improvements in glycemic parameters were most notable in individuals with CFRD. There was no significant change in CGM-measured or self-reported hypoglycemia before and after ETI initiation.
Initiation of ETI in adults with CF was associated with improvement CGM-derived measures of hyperglycemia and glycemic variability with no effect on hypoglycemia. Further studies are needed to investigate underlying etiology of these changes and the long-term impact of ETI on glycemic control in patients with CF.
High rates of newly diagnosed diabetes mellitus (NDDM) have been reported in association with coronavirus disease-2019 (COVID-19). Factors associated with NDDM and long-term glycemic outcomes are not ...known.
Retrospective review of individuals admitted with COVID-19 and diabetes mellitus (DM; based on labs, diagnoses, outpatient insulin use, or severe inpatient hyperglycemia) between March and September 2020, with follow-up through July 2021.
Of 1902 individuals admitted with COVID-19, 594 (31.2%) had DM; 77 (13.0%) of these had NDDM. Compared to pre-existing DM, NDDM was more common in younger patients and less common in those of non-Hispanic White race/ethnicity. Glycemic parameters were lower and inflammatory markers higher in patients with NDDM. In adjusted models, NDDM was associated with lower insulin requirements, longer length of stay, and intensive care unit admission but not death. Of 64 survivors with NDDM, 36 (56.3%) continued to have DM, 26 (40.6%) regressed to normoglycemia or pre-diabetes, and 2 were unable to be classified at a median follow-up of 323 days.
Diabetes diagnosed at COVID-19 presentation is associated with lower glucose but higher inflammatory markers and ICU admission, suggesting stress hyperglycemia as a major physiologic mechanism. Approximately half of such individuals experience regression of DM.
•Patients with newly diagnosed vs. pre-existing diabetes at COVID-19 admission had lower glucose but more severe COVID-19.•After discharge, half of patients with COVID-19 and newly diagnosed diabetes regress to normoglycemia or prediabetes.•Stress hyperglycemia, not β cell destruction, may be the major mechanism for COVID-19-associated newly diagnosed diabetes.
Background: Prospective studies investigating the occurrence of and risk factors for continuous glucose monitoring (CGM) detected hypoglycemia in the inpatient setting are limited.
Methods: In this ...prospective observational study, patients hospitalized on medical and surgical floors and undergoing fingerstick glucose monitoring wore blinded Dexcom G6Pro sensors. Participants with sensor readings <54mg/dL were identified after excluding erroneous readings from compression via manual review. Data from participant survey and chart review were analyzed chi square tests for categorical variables, and t test and Kruskal-Wallis test for continuous variables to identify predictors of hypoglycemia.
Results: CGM data were collected from 268 participants. At least one episode of CGM glucose <54 mg/dL occurred in 30 (11%). Participants with at least one episode of glucose <54mg/dL had longer hospital stay, lower A1c (but also lower hemoglobin level), and were more likely to have type 1 diabetes compared to those without hypoglycemia (Table 1). Forty-six (17%) had what appeared to be a false reading <70 mg/dL due to compression or artifact at least once.
Conclusion: CGM may be helpful in identifying hypoglycemia in hospitalized patients. Further research is needed to identify patient populations who may benefit from inpatient CGM monitoring for prevention of hypoglycemia.
Disclosure
M. O'connor: None. E. Greaux: None. S. J. Russell: Consultant; Beta Bionics, Inc., Senseonics, ConvaTec Inc., Employee; Beta Bionics, Inc., Stock/Shareholder; Beta Bionics, Inc. M. S. Putman: Consultant; Synspira Therapeutics, Other Relationship; Vertex Pharmaceuticals Incorporated, Research Support; Dexcom, Inc. A. Sabean: None. B. Steiner: Stock/Shareholder; Bristol-Myers Squibb Company. H. Zheng: None. J. Yan: None. A. Ashley: None. N. Anandakugan: None. M. M. Calverley: None. R. Bartholomew: None.
Funding
National Institutes of Health (R01DK119699-02S1, T32DK007028); Dexcom, Inc. (to M.O.)
Context:
Bariatric surgery is increasingly popular but may lead to metabolic bone disease.
Objective:
The objective was to determine the rate of bone loss in the 24 months after Roux-en-Y gastric ...bypass.
Design and Setting:
This was a prospective cohort study conducted at an academic medical center.
Participants:
The participants were adults with severe obesity, including 30 adults undergoing gastric bypass and 20 nonsurgical controls.
Outcomes:
We measured bone mineral density (BMD) at the lumbar spine and proximal femur by quantitative computed tomography (QCT) and dual-energy x-ray absorptiometry at 0, 12, and 24 months. BMD and bone microarchitecture were also assessed by high-resolution peripheral QCT, and estimated bone strength was calculated using microfinite element analysis.
Results:
Weight loss plateaued 6 months after gastric bypass but remained greater than controls at 24 months (−37 ± 3 vs −5 ± 3 kg mean ± SEM; P < .001). At 24 months, BMD was 5–7% lower at the spine and 6–10% lower at the hip in subjects who underwent gastric bypass compared with nonsurgical controls, as assessed by QCT and dual-energy x-ray absorptiometry (P < .001 for all). Despite significant bone loss, average T-scores remained in the normal range 24 months after gastric bypass. Cortical and trabecular BMD and microarchitecture at the distal radius and tibia deteriorated in the gastric bypass group throughout the 24 months, such that estimated bone strength was 9% lower than controls. The decline in BMD persisted beyond the first year, with rates of bone loss exceeding controls throughout the second year at all skeletal sites. Mean serum calcium, 25(OH)-vitamin D, and PTH were maintained within the normal range in both groups.
Conclusions:
Substantial bone loss occurs throughout the 24 months after gastric bypass despite weight stability in the second year. Although the benefits of gastric bypass surgery are well established, the potential for adverse effects on skeletal integrity remains an important concern.
The clinical utility and implications of continuous glucose monitoring (CGM) in cystic fibrosis (CF) are unclear.
We examined the correlation between CGM measures and clinical outcomes in adults with ...CF, investigated the relationship between hemoglobin A1c (HbA1c) and CGM-derived average glucose (AG), and explored CGM measures that distinguish cystic fibrosis-related diabetes (CFRD) from normal and abnormal glucose tolerance.
This prospective observational study included 77 adults with CF who had CGM and HbA1c measured at 2 to 3 time points 3 months apart.
Thirty-one of the 77 participants met American Diabetes Association-recommended diagnostic criteria for CFRD by oral glucose tolerance testing and/or HbA1c. In all participants, CGM measures of hyperglycemia and glycemic variability correlated with nutritional status and pulmonary function. HbA1c was correlated with AG (R2 = 0.71, P < 0.001), with no significant difference between this regression line and that previously established in type 1 and type 2 diabetes and healthy volunteers. Cutoffs of 17.5% time > 140 mg/dL and 3.4% time > 180 mg/dL had sensitivities of 87% and 90%, respectively, and specificities of 95%, for identifying CFRD. Area under the curve and percent of participants correctly classified with CFRD were higher for AG, SD, % time > 140, > 180, and > 250 mg/dL than for HbA1c.
CGM measures of hyperglycemia and glycemic variability are superior to HbA1c in distinguishing those with and without CFRD. CGM-derived AG is strongly correlated with HbA1c in adults with CF, with a similar relationship to other diabetes populations. Future studies are needed to investigate CGM as a diagnostic and screening tool for CFRD.
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