Dynamics of Hemoglobin A1c, Body Mass Index, and Rates of Severe Hypoglycemia in 4434 Adults with Type 1 or Type 2 Diabetes After Initiation of Continuous Glucose Monitoring.

Background: Continuous glucose monitoring (CGM) might have beneficial effects on glycemic control and body mass index (BMI) in adults with type 1 (T1D) or type 2 diabetes (T2D). Methods: The diabetes prospective follow-up registry was used to identify individuals with T1D or T2D ≥18 years starting CGM management in 2015 or later and follow-up information available. Hemoglobin A1c (HbA1c), BMI, and event rates of severe hypoglycemia in the year before CGM start were compared with two follow-up periods: (1) CGM use for 3-6 months and (2) CGM use for >6 months. Repeated measurements linear and negative binomial regressions were used (adjustment for sex, age at diabetes onset, and baseline parameters) and stratified by diabetes type. Results: Mean follow-up time was 1.8 years in T1D (n = 2994) and 1.9 years in T2D (n = 1440). In T1D, adjusted mean HbA1c decreased significantly from 7.65% (95% confidence interval: 7.62-7.68) at baseline to 7.54% (7.51-7.57) during follow-up. BMI increased slightly (baseline: 25.4 kg/m2 [25.3-25.5], follow-up >6 months: 25.8 kg/m2 [25.7-25.9]), whereas event rates of severe hypoglycemia were significantly lower after >6 months with CGM (9.0 events/100 patient-years [PY; 8.0-10.1]) compared with baseline (11.3 events/100 PY [10.4-12.2]) in adults with T1D. In T2D, HbA1c decreased from 7.21% (7.17%-7.25%) to 7.00% (6.95%-7.04%) and BMI did not change after CGM initiation. Conclusion: Our results provide real-world evidence on CGM management in adult individuals with T1D or T2D. We suggest strengthening patients' and physicians' readiness toward diabetes technology in T2D and more openness of health insurance to cover cost based on proven benefits.

Transient hypoglycemia as a rare cause of recurring transient loss of consciousness: a case report.

BACKGROUND: Syncopes and transient loss of consciousness affect a large number of patients. Determining the underlying mechanism of a syncope is key to effectively treating and preventing future events. However, given the broad differential diagnosis of transient loss of consciousness, it can be challenging to determine the exact etiology. CASE PRESENTATION: This case presents a 42-year-old Caucasian female patient with recurrent transient loss of consciousness due to a hitherto undiagnosed impaired glucose tolerance and hyperinsulinism. The patient had been thoroughly tested for all typical causes of syncope without finding any causal explanation. An oral glucose tolerance test confirmed rapidly dropping blood glucose levels associated with rapidly fading consciousness as the underlying cause of transient loss of consciousness. Further diagnostic workup revealed that the patient suffered from impaired glucose tolerance and subsequent hyperinsulinism without overt diabetes mellitus. Nutritional counseling including reduction of glucose intake and frequently eating smaller meal portions led to a significant reduction in the frequency of transient loss of consciousness and overall improvement in quality of life. CONCLUSIONS: The current European Society of Cardiology (ESC) guideline on syncope does not list hypoglycemia as a cause of transient loss of consciousness. However, this case report stresses that metabolic dysregulation can indeed lead to self-limited transient loss of consciousness. Thus, in the case of recurrent syncope with an unclear underlying mechanism, physicians should consider transient hypoglycemia and metabolic workup as a possible differential diagnosis.

Life-threatening Autoimmune Cardiomyopathy Reproducibly Induced in a Patient by Checkpoint Inhibitor Therapy.

Checkpoint inhibitors induce a plethora of immune-related adverse events (irAEs) including autoimmune colitis, hepatitis, endocrinopathies, and rarer side effects like neuritis. Here, a case of autoimmune cardiomyopathy (grade 3 CTCAE) and myocarditis under combination therapy with nivolumab plus ipilimumab in a 72-year-old melanoma patient is reported. Treatment induced a partial response for 14 months. However, after 10 infusions the patient developed dyspnea, edema of the legs, ascites and a weight gain of 10 kg because of a decompensated heart insufficiency with a reduced ejection fraction from formerly 48%-50% to 15%. Ischemia and viral infections were ruled out. Histopathology showed hypertrophic myocarditis with interstitial lymphocytes. Prednisolone improved the patient's condition within 3 days, leading to a 25% and 30% ejection fraction after 2 and 8 weeks, respectively, and clinical symptoms subsided completely. Importantly, reinduction of anti-PD1 therapy resulted in a flare of myocarditis. Awareness for potentially life-threatening irAE of checkpoint inhibitors like autoimmune cardiomyopathy and myocarditis is crucial to rapidly initiate adequate treatment.

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network.

BACKGROUND: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. METHODS AND FINDINGS: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patients delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. CONCLUSION: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects.

Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies.

BACKGROUND: Mutations in the NOTCH3 gene are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is an important cause of stroke in young adults. Mutations are typically located within epidermal growth factor-like repeat domains in the extracellular part of the Notch3 receptor. Identification of the mutation is critical for genetic counseling and testing of relatives at risk. OBJECTIVES: To identify the spectrum of NOTCH3 mutations in CADASIL and to discuss the implications for diagnostic strategies. DESIGN: Screening for NOTCH3 mutations was performed in 125 unrelated German CADASIL patients with biopsy-proven disease by direct sequencing of exons coding for epidermal growth factor-like repeats. Results were compared with those of previously published studies. RESULTS: We detected 54 distinct mutations (117 missense mutations and 3 in-frame deletions) in 120 (96.0%) of the 125 patients. Of the mutations, 58.3% were located in exon 4 and 85.8% in exons 2 through 6. In 5 patients (4.0%), no mutation was identified. CONCLUSIONS: Almost 90% of mutations could be detected within a few exons (exons 2-6). Thus, genetic testing should initially be focused on these exons, with some variation depending on the population in whom it is being performed. Yet, genetic testing for CADASIL is associated with a nameable proportion of false-negative results. Cases with a high index of clinical suspicion should be investigated by skin biopsy if genetic testing is negative.