Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports

Abstract Background Since 2011 six immune checkpoint inhibitors (ICI) have been approved to treat patients with many advanced solid tumor and hematological malignancies to improve their prognosis. Case reports of their endocrine immune-related adverse events [irAEs]) are increasingly published as more real-world patients with these malignancies are treated with these drugs. They alert physicians of a drug’s AEs (which may change during a drug’s life cycle) and contribute to post-marketing safety surveillance. Using a modified framework of Arksey and O’Malley, we conducted a scoping review of the spectrum and characteristics of ICI-induced endocrinopathies case reports before and after ICIs are marketed. Methods In July 2017, we searched, without date and language restrictions, 4 citation databases for ICI-induced endocrinopathies. We also hand-searched articles’ references, contents of relevant journals, and ran supplemental searches to capture recent reports through January 2018. For this study, a case should have information on type of cancer, type of ICI, clinical presentation, biochemical tests, treatment plus temporal association of ICI initiation with endocrinopathies. Two endocrinologists independently extracted the data which were then summarized and categorized. Results One hundred seventy nine articles reported 451 cases of ICI-induced endocrinopathies - 222 hypopituitarism, 152 thyroid disorders, 66 diabetes mellitus, 6 primary adrenal insufficiencies, 1 ACTH-dependent Cushing’s syndrome, 1 hypoparathyroidism and 3 diabetes insipidus cases. Their clinical presentations reflect hormone excess or deficiency. Some were asymptomatic and others life-threatening. One or more endocrine glands could be affected. Polyglandular endocrinopathies could present simultaneously or in sequence. Many occur within 5 months of therapy initiation; a few occurred after ICI was stopped. Mostly irreversible, they required long-term hormone replacement. High dose steroids were used when non-endocrine AEs coexisted or as therapy in adrenal insufficiency. There was variability of information in the case reports but all met the study criteria to make a diagnosis. Conclusions The spectrum of ICI-induced endocrinopathies is wide (5 glands affected) and their presentation varied (12 endocrinopathies). Clinical reasoning integrating clinical, biochemical and treatment information is needed to properly diagnose and manage them. Physicians should be vigilant for their occurrence and be able to diagnose, investigate and manage them appropriately at onset and follow-up.https://deepblue.lib.umich.edu/bitstream/2027.42/147443/1/40842_2018_Article_73.pd

Gender differences in diabetes self-care in adults with type 1 diabetes: Findings from the T1D Exchange clinic registry

Aims To evaluate gender differences in diabetes self-care components including glycemic, blood pressure and lipid control, utilization of diabetes technologies and acute diabetes complications in adults with type 1 diabetes. Methods A total of 9,481 participants >18 years were included in the analysis, 53% were female. Variables of interest included glycemic control measured by HbA1c, systolic/diastolic blood pressures, presence of dyslipidemia, insulin delivery modality, and rates of acute complications. Results Glycemic control was similar in women and men (mean HbA1c in both groups: 8.1% ± 1.6% (64 ± 16 mmol/mol), (p = 0.54). More women used insulin pump therapy (66% vs. 59%, p < 0.001) but use of sensor technology was similar (p < = 0.42). Women had higher rates of diabetic ketoacidosis (DKA) (5% vs. 3%, p < 0.001) and eating disorders (1.7% vs. 0.1%, p < 0.001). Severe hypoglycemia rates were not different between men and women (p = 0.42). Smoking (6% vs 4%, p < 0.001), systolic (125 ± 14.2 vs. 121 ± 14.4, p < 0.001) and diastolic blood pressure (73.3 ± 9.5 vs. 72.2 ± 9.3, p < 0.001) and rate of dyslipidemia (28% vs. 23%, p < 0.001) were higher in men. Conclusion While glycemic control in type 1 diabetes was similar regardless of gender, rates of DKA and eating disorders were higher in women while rates of smoking, hypertension and dyslipidemia were higher in men

Psychosocial Care for People With Diabetic Neuropathy : Time for Action

Psychological factors and psychosocial care for individuals with diabetic neuropathy (DN), a common and burdensome complication of diabetes, are important but overlooked areas. In this article we focus on common clinical manifestations of DN, unremitting neuropathic pain, postural instability, and foot complications, and their psychosocial impact, including depression, anxiety, poor sleep quality, and specific problems such as fear of falling and fear of amputation. We also summarize the evidence regarding the negative impact of psychological factors such as depression on DN, self-care tasks, and future health outcomes. The clinical problem of underdetection and undertreatment of psychological problems is described, together with the value of using brief assessments of these in clinical care. We conclude by discussing trial evidence regarding the effectiveness of current pharmacological and nonpharmacological approaches and also future directions for developing and testing new psychological treatments for DN and its clinicalmanifestations

The Association Between Heart Rate and Glycemic Status in the National Health and Nutrition Examination Surveys

Evidence suggests that heart rate (HR) is a prognostic factor for cardiovascular disease (CVD), for which persons with diabetes are at increased risk. The objective of this article is to determine the association between HR and glycemic status in a nationally representative sample of US adults, and, among adults with diagnosed diabetes, the association between HR and hemoglobin A1c (HbA1c) level. A cross-sectional study was conducted. The setting of this study is the National Health and Nutrition Examination Surveys, 2011 to 2016. US general adult (age ≥ 20 years) population who had information on glycemic status based on self-report, HbA1c, and fasting plasma glucose (N = 8562). There was no intervention. The main outcome measure of this study was mean HR (beats per minute). After adjustment for examination time, age, other demographic characteristics, health insurance, health behaviors, body mass index, CVD and kidney disease, and taking antihypertensive medications, mean HR was significantly higher for those with diagnosed (75 bpm), undiagnosed diabetes (75 bpm), and prediabetes (73 bpm) compared to those with normoglycemia (71 bpm, P < .05 for all); this association was robust both for men and women. Mean HR increased with increasing HbA1c level among individuals with diagnosed diabetes independent of other risk factors (HbA1c < 7.0% [< 53 mmol/mol], 73 bpm vs A1c ≥ 11.0% [≥ 97mmol/mol], 79 bpm, P < .001); this association was most pronounced for women. Adjusted mean HR was higher among individuals with diabetes and increased glycemia, which may reflect underlying autonomic and/or myocardial dysfunction among those with diabetes

The Contemporary Prevalence of Diabetic Neuropathy in Type 1 Diabetes: Findings From the T1D Exchange

To evaluate the contemporary prevalence of diabetic peripheral neuropathy (DPN) in participants with type 1 diabetes in the T1D Exchange Clinic Registry throughout the U.S. DPN was assessed with the Michigan Neuropathy Screening Instrument Questionnaire (MNSIQ) in adults with ≥5 years of type 1 diabetes duration. A score of ≥4 defined DPN. Associations of demographic, clinical, and laboratory factors with DPN were assessed. Among 5,936 T1D Exchange participants (mean ± SD age 39 ± 18 years, median type 1 diabetes duration 18 years [interquartile range 11, 31], 55% female, 88% non-Hispanic white, mean glycated hemoglobin [HbA ] 8.1 ± 1.6% [65.3 ± 17.5 mmol/mol]), DPN prevalence was 11%. Compared with those without DPN, DPN participants were older, had higher HbA , had longer duration of diabetes, were more likely to be female, and were less likely to have a college education and private insurance (all < 0.001). DPN participants also were more likely to have cardiovascular disease (CVD) ( < 0.001), worse CVD risk factors of smoking ( = 0.008), hypertriglyceridemia ( = 0.002), higher BMI ( = 0.009), retinopathy ( = 0.004), reduced estimated glomerular filtration rate ( = 0.02), and Charcot neuroarthropathy ( = 0.002). There were no differences in insulin pump or continuous glucose monitor use, although DPN participants were more likely to have had severe hypoglycemia ( = 0.04) and/or diabetic ketoacidosis ( < 0.001) in the past 3 months. The prevalence of DPN in this national cohort with type 1 diabetes is lower than in prior published reports but is reflective of current clinical care practices. These data also highlight that nonglycemic risk factors, such as CVD risk factors, severe hypoglycemia, diabetic ketoacidosis, and lower socioeconomic status, may also play a role in DPN development

Symptomatic diabetic autonomic neuropathy in type 1 diabetes (T1D): Findings from the T1D exchange

We aimed to evaluate the contemporary prevalence of and risk factors for symptomatic diabetic autonomic neuropathy (DAN) in participants with type 1 diabetes (T1D) enrolled in the T1D Exchange Clinic Registry. DAN symptoms and severity were assessed with the Survey of Autonomic Symptoms (SAS) in adults with ≥5 years of T1D participating in the T1D Exchange from years 2010–2017. Associations of demographic, clinical, and laboratory factors with symptomatic DAN were assessed. Of the 4919 eligible T1D participants, 965 (20%) individuals completed the SAS questionnaire [mean age 40 ± 17 years, median diabetes duration 20 years (IQR: 13,34), 64% female, 90% non-Hispanic White, and 82% with private insurance]. DAN symptoms were present in 166 (17%) of responders with 72% experiencing moderate severity symptoms or worse. Symptomatic DAN participants had higher hemoglobin A1c (p = 0.03), longer duration (p = 0.004), were more likely to be female (p = 0.03), and more likely to have lower income (p = 0.03) versus no DAN symptoms. Symptomatic DAN was associated with diabetic peripheral neuropathy (p < 0.0001), smoking (p = 0.002), cardiovascular disease (p = 0.02), depression (p < 0.001), and opioid use (p = 0.004). DAN symptoms are common in T1D. Socioeconomic factors and psychological comorbidities may contribute to DAN symptoms and should be explored further. •17% of adults with type 1 diabetes experience diabetic autonomic neuropathy symptoms.•Glycemic exposure remains a major risk factor for symptomatic diabetic autonomic neuropathy in type 1 diabetes.•Vascular risk factors are also associated with symptomatic diabetic autonomic neuropathy in type 1 diabetes.•Low socioeconomic status, depression, and use of opioids are novel risk factors for symptomatic diabetic autonomic neuropathy in type 1 diabetes