A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings

BackgroundA composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data.MethodsWe assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation.ResultsThe analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals.ConclusionThe GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments

Diabetes DeMysTiFieD

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Toward effective interventions to reduce diabetes distress among adults with type 1 diabetes: Enhancing Emotion regulation and cognitive skills.

ObjectiveWe tested three models to determine how improvements in emotion regulation (ER) and cognitive skills (CS) as a result of intervention operate to affect reductions in diabetes distress DD.MethodsChange data were drawn from the baseline and 9-month T1-REDEEM trial. Adults with type 1 diabetes were recruited from several U.S. states and Toronto, Canada. A primary and two alternative structural equation models were tested to explore the directionality of effect: primary model - changes in ER and CS drive changes in DD; reverse model - changes in DD drive changes in ER and CS; and bidirectional model - changes in ER, CS and DD occur together with no directionality.ResultsAll three models displayed a good fit to the data. The primary model indicated 7 significant directional pathways: improvements in ER and CS operate together to drive reductions in DD. The reverse model only indicated that reductions in DD affected changes in one CS variable; and the bidirectional model indicated only that these results were bidirectional. Reductions in all tested domains of DD occurred together.ConclusionsImprovements in ER and CS drive reductions in DD.Practice implicationsInterventions to reduce high DD should focus on improving ER and CS

A Case of Hypercalcemia from PTHrP-Producing Fibromyxoid Sarcoma Responsive to Glucocorticoid Therapy.

The treatment of parathyroid hormone-related protein (PTHrP)-mediated hypercalcemia of malignancy includes treating the malignancy, intravenous fluids, and anti-resorptive therapies such as zoledronic acid or denosumab. PTHrP-mediated hypercalcemia has been reported in benign conditions such as systemic lupus erythematous (SLE) and sarcoidosis and appears to be responsive to glucocorticoids. We report a case of PTHrP-induced hypercalcemia due to a malignancy-low grade fibromyxoid sarcoma-that responded to glucocorticoid treatment. This is the first report of glucocorticoids controlling PTHrP-mediated hypercalcemia of malignancy. Immunohistochemistry of the surgical pathology localized PTHrP staining to the vascular endothelial cells within the tumor. Further studies are needed to elucidate the mechanism of glucocorticoid action in the treatment of PTHrP-mediated hypercalcemia of malignancy

A multidisciplinary approach to optimizing care of patients treated with alpelisib.

PURPOSE: The oral, α-specific phosphatidylinositol-3-kinase (PI3Kα) inhibitor alpelisib is the first PI3K inhibitor approved for the treatment of advanced breast cancer. As alpelisib is a relatively new therapeutic option, specific guidance and a multidisciplinary approach are needed to provide optimal patient care. The primary objective of this manuscript is to provide comprehensive guidance on minimizing and managing adverse events (AEs) for patients with advanced breast cancer who are receiving alpelisib. METHODS: Clinical studies, prescribing information, published literature, and relevant guidelines were reviewed to provide recommendations on the prevention and management of alpelisib-associated AEs. RESULTS: The most common AEs associated with alpelisib in the phase 3 SOLAR-1 trial were hyperglycemia and rash (which are considered on-target effects of PI3Kα inhibition) and gastrointestinal AEs, including diarrhea, nausea, and decreased appetite. These AEs require regular monitoring, early recognition, and prompt initiation of appropriate treatment. In addition, there are effective strategies to reduce the onset and severity of frequently observed AEs-in particular, onset of hyperglycemia and rash may be reduced by lifestyle changes (such as reduced intake of carbohydrates and regular exercise) and antihistamine prophylaxis, respectively. To reduce risk of severe hyperglycemia, it is essential to achieve adequate glycemic control prior to initiation of alpelisib treatment. CONCLUSION: Overall, alpelisib-associated AEs are generally manageable with prompt recognition, regular monitoring, and appropriate intervention, preferably with a multidisciplinary approach

Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs.

Testosterone (T) and related androgens are performance enhancing drugs (PEDs) abused by some athletes to gain competitive advantage. To monitor unauthorized androgen abuse, doping control programs use mass spectrometry (MS) to detect androgens, synthetic anabolic-androgenic steroids (AASs) and their metabolites in an athlete's urine. AASs of unknown composition will not be detected by these procedures. Since AASs achieve their anabolic effects by activating the Androgen Receptor (AR), cell-based bioassays that measure the effect of a urine sample on AR activity are under investigation as complementary, pan-androgen detection methods. We evaluated an AR BioAssay as a monitor for androgen activity in urine pre-treated with glucuronidase, which releases T from the inactive T-glucuronide that predominates in urine. AR BioAssay activity levels were expressed as 'T-equivalent' concentrations by comparison to a T dose response curve. The T-equivalent concentrations of androgens in the urine of hypogonadal participants supplemented with T (in whom all androgenic activity should arise from T) were quantitatively identical to the T measurements conducted by MS at the UCLA Olympic Analytical Laboratory (0.96 ± 0.22). All 17 AASs studied were active in the AR BioAssay; other steroids were inactive. 12 metabolites of 10 commonly abused AASs, which are used for MS monitoring of AAS doping because of their prolonged presence in urine, had reduced or no AR BioAssay activity. Thus, the AR BioAssay can accurately and inexpensively monitor T, but its ability to monitor urinary AASs will be limited to a period immediately following doping in which the active AASs remain intact

Daily Negative Mood Affects Fasting Glucose in Type 2 Diabetes

Objective—To examine the relationship between mood and blood glucose in a 21 day daily diary study. Design—During a home visit, information was gathered from two hundred six persons with type 2 diabetes regarding demographics, disease characteristics and treatment, and depressive symptoms. They had blood drawn at a laboratory, yielding HbA1C. The participants were then telephoned each evening for 21 days and were asked about their positive and negative mood during the past 24 hours. They also tested their blood glucose upon rising in the morning. Main Outcome Measures—The main outcomes measures were positive and negative affect and fasting glucose. Results—Multilevel analyses revealed a relationship between negative affect on one day and morning glucose on the next day. There was no such relationship between positive affect and glucose, nor was there a comparable effect of glucose on one day and either positive or negative affect on the next day. Conclusion—The observed relationship between mood and blood glucose appears to be due to negative affect, not positive, with no evidence of a lagged effect of glucose on mood

Economic costs of implementing group interventions to reduce diabetes distress in adults with type 1 diabetes mellitus in the T1-REDEEM trial

AimsThis study evaluated the implementation costs of two group interventions, one focused on diabetes education (KnowIt) and one focused directly on diabetes distress (OnTrack), that reduced diabetes distress and HbA1C in adults with poorly controlled type 1 diabetes (T1DM) in the T1-REDEEM trial.MethodsResources used to provide interventions were enumerated using activity-based micro-costing methods. Costs were assigned to resources in 2017 US dollars. US median wage and benefit rates were used to calculate costs of staff time. Cost per unit change was calculated for diabetes distress and HbA1C.ResultsFor both interventions, per participant implementation costs were approximately $250 and cost per 1.0 percentage point (11 mmol/mol) change in HbA1C was$1400. Cost per unit change in diabetes distress was $364 for KnowIt and$335 for OnTrack. No statistically significant differences in costs were observed.ConclusionsThis is the first study to examine the costs of implementing interventions targeting diabetes distress in the context of T1DM. Both interventions had per participant implementation costs in the lower end of the range of previously examined diabetes self-management interventions ($219 to$5390). These inventions and their costs merit further attention because reducing diabetes distress may impact long term T1DM outcomes.Clinical trials registrationClinicalTrials.govNCT02175732