Sodium-Glucose Cotransporter 2 Inhibitors Should Be Avoided for the Inpatient Management of Hyperglycemia.

OBJECTIVE: Hyperglycemia in patients with type 2 diabetes mellitus is frequently encountered in the hospital setting. The recent guidelines for the management of inpatient hyperglycemia have included the use of dipeptidyl peptidase 4 inhibitors as an alternative to standard insulin therapy in select patients. This raises the question of the inpatient use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), which have gained increasing popularity in the outpatient setting because of beneficial cardiovascular and renal outcomes. This article describes the risks associated with the use of SGLT2i for the management of inpatient hyperglycemia. METHODS: A literature review was performed using PubMed and Google Scholar for studies assessing the inpatient use of SGLT2i. Search terms included "SGLT2 inhibitors," "euglycemic DKA," "inpatient hyperglycemia," "DPP4 inhibitors," "hypovolemia," and "urinary tract infections." Studies not written in English were excluded. Forty-eight articles were included. RESULTS: Review of the literature showed significant safety concerns with the use of SGLT2i for the inpatient management of hyperglycemia. Hospitalized patients treated with SGLT2i were at increased risk of diabetic ketoacidosis, euglycemic diabetic ketoacidosis, hypovolemia, and urinary tract infections. When compared head-to-head, SGLT2i were not more effective for inpatient glycemic control than dipeptidyl peptidase 4 inhibitors and did not reduce insulin requirements when used in combination with insulin. Although SGLT2i can be considered for the treatment of congestive heart failure, they should be started close to or at the time of discharge. CONCLUSION: Although SGLT2i are a preferred pharmacotherapy class for the outpatient management of type 2 diabetes mellitus, there are considerable safety concerns when using them in a hospital setting, and avoidance is recommended.

Racial and ethnic differences in post-traumatic stress trajectories in breast cancer survivors.

PURPOSE: To describe differences in post-traumatic stress (PTS) symptoms over time among racial and ethnic minoritized breast cancer survivors (BCS) with comorbid diabetes. DESIGN: In a multisite longitudinal study, post-traumatic stress was evaluated at baseline, 6 and 12 months through self-reported questionnaires (Impact of Events Scale-Revised [IES-R]). PARTICIPANTS: One hundred and seventy-eight post-treatment BCS with diabetes were recruited from three tertiary medical centers. FINDINGS: Relative to non-Hispanic White women, minoritized women reported higher total IES-R scores at all time points. In the adjusted model, Latina women reported persistently higher IES-R total scores and Latina, and 'Other' women reported higher avoidance scores. CONCLUSIONS: Minoritized BCS with comorbid diabetes report higher rates of cancer related PTS that persist over 12 months. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: Post diagnosis PTS evaluation and support is important in survivorship and primary care practices. Linkage to socially and culturally sensitive community support may be warranted.

The impact of cognitive impairment on self-regulatory styles in breast cancer survivors.

OBJECTIVE: Cognitive impairment (CI) is highly prevalent in breast cancer survivors (BCS), and can be a barrier to health-promoting behaviours. However, the ways in which CI may affect self-regulation or motivation to perform such behaviours have not been explored. We assessed if BCS with CI report greater extrinsic self-regulation compared to those without CI and if this relationship persists after controlling for depression. METHODS: We recruited BCS with diabetes and assessed cognition and motivation to perform healthy diabetes management behaviours (e.g., diet and exercise). Participants completed a cognitive battery evaluating attention, working memory, executive functioning (EF), processing speed (PS), language and memory. The Treatment Self-Regulation Questionnaire (TSRQ) assessed intrinsic versus extrinsic motivation. Depression was determined by a score ≥16 on the Center for Epidemiological Studies Depression Scale. Wilcoxon rank-sum test compared associations between CI and TSRQ scores. RESULTS: Participants were 118 older adults (mean age 65 years). Participants with CI in the following domains had higher extrinsic self-regulation scores compared to those without CI: attention (p < 0.01), PS (p = 0.01), EF (p < 0.01), language (p = 0.02; p = 0.04) and memory (p = 0.04; p = 0.03). After adjusting for depression, the relationship between CI and higher extrinsic self-regulation scores remained significant. CONCLUSIONS: BCS with CI appear to rely more on external sources of motivation to perform health behaviours, regardless of depression. Future studies and interventions to improve health behaviours should consider screening for CI and involving caregivers for those with CI to improve outcomes.

Racial and ethnic disparities in post-traumatic stress and illness coherence in breast cancer survivors with comorbid diabetes.

CONTEXT: Breast cancer survivors (BCS) with comorbid diabetes mellitus (DM) and of racial and ethnic minority status are at higher risk of cancer-related post-traumatic stress (PTS) and severe illness beliefs. These affective and cognitive outcomes influence self-management and treatment adherence in patients with chronic conditions, yet little is known regarding the interplay of these processes in diverse BCS with comorbid DM. OBJECTIVES: The purposes of this study were to (1) describe racial and ethnic differences in cancer-related PTS and illness perceptions; and (2) examine the relationship between PTS and illness perceptions in BCS with comorbid DM. METHODS: Female BCS with DM completed measures of cancer related stress (Impact of Events Scale-Revised) and cancer and DM illness perception (Illness Perception Questionnaire-Revised). Logistic regression analyses were used to assess the association between PTS, race and illness perceptions. RESULTS: Of the 135 BCS with comorbid DM, the mean (standard deviation) age was 65.3 (7.1) years, 38% were Black, 31% Non-Hispanic White (NHW), 13% Hispanic/Latina, and 18% were "other." Minority women were more likely to report cancer-related PTS (p < 0.01). In adjusted analyses, PTS was associated with chronicity (odds ratio [OR] = 9.79, p = 0.005), time-cycle (OR = 6.71, p = 0.001), negative consequences (OR = 3.95, p = 0.018), and negative emotional impact (OR = 12.63, p < 0.001) of cancer. CONCLUSION: Minority BCS with comorbid DM report higher rates of cancer-related PTS and lower cancer illness coherence relative to NHW survivors. Cancer-related PTS influences cancer and DM illness perceptions. Culturally sensitive care is needed to improve these outcomes in minority BCS. KEY MESSAGE: This article presents findings from a cross sectional cohort of an understudied population of racially and ethnically diverse BCS with comorbid diabetes. The results indicate that the occurrence of PTS is significantly higher in racial and ethnic minority women and is strongly associated with more severe illness perceptions.

Galantamine alleviates inflammation and other obesity-associated complications in high-fat diet-fed mice.

Obesity, a serious and growing health threat, is associated with low-grade inflammation that plays a role in mediating its adverse consequences. Previously, we have discovered a role for neural cholinergic signaling in controlling inflammation, and demonstrated that the cholinergic agent galantamine suppresses excessive proinflammatory cytokine release. The main objective of this study was to examine the efficacy of galantamine, a clinically-approved drug, in alleviating obesity-related inflammation and associated complications. After 8 wks on a high-fat diet, C57BL/6J mice were treated with either galantamine (4 mg/kg, intraperitoneally [i.p.]) or saline for 4 wks in parallel with mice on a low-fat diet and treated with saline. Galantamine treatment of obese mice significantly reduced body weight, food intake, abdominal adiposity, plasma cytokine and adipokine levels, and significantly improved blood glucose, insulin resistance and hepatic steatosis. In addition, galantamine alleviated impaired insulin sensitivity and glucose intolerance significantly. These results indicate a previously unrecognized potential of galantamine in alleviating obesity, inflammation and other obesity-related complications in mice. These findings are of interest for studying the efficacy of this clinically-approved drug in the context of human obesity and metabolic syndrome.

Galantamine alleviates inflammation and insulin resistance in patients with metabolic syndrome in a randomized trial.

BACKGROUND: Metabolic syndrome (MetS) is an obesity-driven condition of pandemic proportions that increases the risk of type 2 diabetes and cardiovascular disease. Pathophysiological mechanisms are poorly understood, though inflammation has been implicated in MetS pathogenesis. The aim of this study was to assess the effects of galantamine, a centrally acting acetylcholinesterase inhibitor with antiinflammatory properties, on markers of inflammation implicated in insulin resistance and cardiovascular risk, and other metabolic and cardiovascular indices in subjects with MetS. METHODS: In this randomized, double-blind, placebo-controlled trial, subjects with MetS (30 per group) received oral galantamine 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo. The primary outcome was inflammation assessed through plasma levels of cytokines and adipokines associated with MetS. Secondary endpoints included body weight, fat tissue depots, plasma glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol (total, HDL, LDL), triglycerides, BP, heart rate, and heart rate variability (HRV). RESULTS: Galantamine resulted in lower plasma levels of proinflammatory molecules TNF (-2.57 pg/ml [95% CI -4.96 to -0.19]; P = 0.035) and leptin (-12.02 ng/ml [95% CI -17.71 to -6.33]; P < 0.0001), and higher levels of the antiinflammatory molecules adiponectin (2.71 µg/ml [95% CI 1.93 to 3.49]; P < 0.0001) and IL-10 (1.32 pg/ml, [95% CI 0.29 to 2.38]; P = 0.002) as compared with placebo. Galantamine also significantly lowered plasma insulin and HOMA-IR values, and altered HRV. CONCLUSION: Low-dose galantamine alleviates inflammation and insulin resistance in MetS subjects. These findings support further study of galantamine in MetS therapy. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02283242. FUNDING: Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, and the NIH.

Hypercalcemia of Malignancy and Colorectal Cancer.

Our aim is to describe the association between colorectal cancer (CRC) and humoral hypercalcemia of malignancy (HHM). Causes of hypercalcemia of malignancy include parathyroid hormone-related peptide (PTHrP) secretion, local osteolysis, calcitriol production and ectopic parathyroid hormone (PTH) secretion. Hypercalcemia of malignancy in patients with CRCs is a rare scenario. A patient with anal squamous cell carcinoma was admitted with hypercalcemia, suppressed PTH and hypophosphatemia. He was found to have metastatic anal squamous cell carcinoma to the liver. Further evaluation revealed elevated PTHrP and 1,25-dihydroxyvitamin D and low 25-hydroxyvitamin D. Over a 5-month course, the hypercalcemia responded poorly to bisphosphonates, transiently to prednisone, but showed marked improvement with chemotherapy. A review of English language publications in Pubmed and a reference search of retrieved articles revealed 29 cases of CRC causing PTHrP-mediated hypercalcemia. Most patients were middle-aged men (mean ± SD: 56.7 ± 13.4 years), with advanced metastatic cancer (85% with hepatic metastasis) and severe hypercalcemia (mean ± SD: 15.6 ± 1.9 mg/dL, 62% with Ca > 14). This condition is associated with high mortality (79%) and short survival (median 54.5 days, CI: 21 - 168). Despite being uncommon, HHM (PTHrP-mediated) should be considered in patients with metastatic CRC presenting with hypercalcemia. Clinicians should be aware that combined etiologies may be present, particularly in cases of resistant hypercalcemia. Treatment of the underlying malignancy is essential for calcium control.