Impact of personalized diabetes care on distress and treatment satisfaction in people with breast cancer.

AIMS: In patients with breast cancer (BCa) and diabetes (DM), diabetes distress (DD) and treatment satisfaction (DTS) can influence BCa management and outcomes. We assessed the impact of implementing a personalized diabetes care model in patients with BCa. METHODS: Patients in active treatment or surveillance for BCa with an HbA1c > 53 mmol/mol (7%) or random blood glucose >11.1 mmol/L were included. Participants were offered continuous glucose monitoring (CGM), virtual care and a dedicated diabetes provider for 6 months. Primary outcomes included DD measured by the Diabetes Distress Survey (DDS) and DTS measured by the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Questionnaires were conducted at 0, 3 and 6 months. RESULTS: Thirty-one women were enrolled (median age 61, IQR 49.0-69.0). Compared to baseline, the mean DDS score was lower at both 3 months (2.2 vs. 1.8 [n = 27], p = 0.004, SD = 0.70) and 6 months (2.3 vs. 1.8 [n = 23], p = 0.002, SD = 0.70). The mean DTSQ score was higher at 3 months (baseline: 20.5 vs. 3 months: 28.7 [n = 28], p < 0.001, SD = 9.2) and 6 months (baseline: 20.4 vs. 6 months: 30.0 [n = 26], p < 0.001, SD = 9.7). CONCLUSIONS: Personalized diabetes care models that emphasize remote management and optimize access for those with BCa may lower DD and improve DTS.

Perioperative Identification and Management of Hyperglycemia in Orthopaedic Surgery.

➤: The consequences of undermanaged perioperative hyperglycemia are notable and can have a serious impact on adverse postoperative outcomes, especially surgical site infections and periprosthetic joint infections (PJIs). ➤: Preoperative screening of hemoglobin A1c with a goal threshold of <7.45% is ideal. ➤: There are a variety of risk factors that contribute to hyperglycemia that should be considered in the perioperative period, including glucocorticoid use, nutritional factors, patient-specific factors, anesthesia, and surgery. ➤: There are expected trends in the rise, peak, and fall of postoperative blood glucose levels, and identifying and treating hyperglycemia as swiftly as possible are the fundamental aims of treatment and improved glucose control. Performing frequent postoperative blood glucose monitoring (in the post-anesthesia care unit, on the day of surgery at 1700 and 2100 hours, and in the morning of postoperative day 1) should be considered to allow for the early detection of alterations in glucose metabolism. In addition, instituting a postoperative dietary restriction of carbohydrates should be considered. ➤: The use of insulin as a hypoglycemic agent in orthopaedic patients is relatively safe and is an effective means of controlling fluctuating blood glucose levels. Insulin therapy should be administered to treat hyperglycemia at ≥140 mg/dL when fasting and ≥180 mg/dL postprandially. Insulin therapy should be ceased at blood glucose levels of <110 mg/dL; however, monitoring for glycemic dysregulation should be continued. In all cases of complex diabetes, consultation with diabetes specialty services should be considered. ➤: The emerging use of technology, including continuous subcutaneous insulin pump therapy and continuous glucose monitoring, is an exciting area of further research and development as such technology can more immediately detect and correct aberrations in blood glucose levels.

The Effects of Diabetes and Glycemic Control on Cancer Outcomes in Individuals With Metastatic Breast Cancer.

BACKGROUND: It is unclear whether diabetes and glycemic control affects the outcomes of breast cancer, especially among those with metastatic disease. This study aims to determine the impact of diabetes and hyperglycemia on cancer progression and mortality in individuals with metastatic breast cancer (MBC). METHODS: Patients with a diagnosis of MBC between 2010 and 2021 were identified using the MBC database at 2 academic institutions. We evaluated the effects of diabetes and glycemic control on overall survival (OS) and time to next treatment (TTNT). RESULTS: We compared 244 patients with diabetes (median age 57.6 years) to 244 patients without diabetes (matched for age, sex, ethnicity, and receptor subtype). OS at 5 years [diabetes: 54% (95% CI 47-62%) vs controls: 56% (95% CI 49-63%), P = 0.65] and TTNT at 1 year [diabetes: 43% (95% CI 36-50%) vs controls: 44% (95% CI 36-51%), P = 0.33] were similar between groups. A subgroup analysis comparing those with good glycemic control and those with poor glycemic control among patients with specific receptor subtype profiles showed no differences in OS at 5 years or TTNT at 1 year. In an 8-year landmark subgroup analysis, there was worse OS among individuals with diabetes compared to controls, and OS was found to be better among those with good glycemic control compared to those with poor control. CONCLUSIONS: Diabetes was not associated with increased mortality in individuals with MBC at 5 years. However, diabetes and hyperglycemia were associated with worse OS among a cohort of longer-term survivors. These findings suggest that individualized diabetes and glycemic goals should be considered in patients with MBC.

Factors leading to alpelisib discontinuation in patients with hormone receptor positive, human epidermal growth factor receptor-2 negative breast cancer.

PURPOSE: Alpelisib is a phosphoinositide-3-kinase inhibitor approved for hormone-receptor-positive, PIK3CA-mutated metastatic breast cancer. However, length of drug exposure, maximum-tolerated dose, and therefore clinical response can vary significantly outside of the trial setting. This study evaluates our center's "real world" experience with alpelisib and focuses on duration of therapy and factors associated with cancer progression. METHODS: Patients receiving alpelisib at our center between 2019 and 2021 were identified. We evaluated duration of alpelisib therapy and the causative reasons for drug discontinuation. The association of drug duration and dose with subsequent cancer progression were assessed, along with the association between hyperglycemia during alpelisib therapy and cancer progression. RESULTS: Sixty-two women prescribed alpelisib were included (mean age 61 years). Disease progression was the most common reason for drug discontinuation, while discontinuation within 30 days was primarily attributed to adverse events (AEs). Among those who progressed, median time to progression was longer in those on alpelisib for > 90 days compared with those on alpelisib for ≤ 90 days (187 vs. 77 days, p < 0.001). At 200 days, freedom from progression was greater for those on alpelisib for > 90 days compared to those receiving therapy for ≤ 90 days (59% vs. 19%, p = 0.001). Median blood glucose as a continuous variable was associated with disease progression (HR 1.01, 95% CI 1.00-1.02, p = 0.02). CONCLUSION: While progression of disease is the largest contributor to alpelisib discontinuation, AEs are the leading cause for early drug cessation. Shorter alpelisib exposure is associated with greater cancer progression. Further studies are needed to determine the impact of sustained hyperglycemia on cancer progression.

Patient-Centered Diabetes Care of Cancer Patients.

PURPOSE OF REVIEW: There is a bidirectional relationship between cancer and diabetes, with one condition influencing the prognosis of the other. Multiple cancer therapies cause diabetes including well-established medications such as glucocorticoids and novel cancer therapies such as immune checkpoint inhibitors (CPIs) and phosphoinositide 3-kinase (PI3K) inhibitors. RECENT FINDINGS: The nature and severity of diabetes caused by each therapy differ, with some predominantly mediated by insulin resistance, such as PI3K inhibitors and glucocorticoids, while others by insulin deficiency, such as CPIs. Studies have demonstrated diabetes from CPIs to be more rapidly progressing than conventional type 1 diabetes. There remains a scarcity of published guidance for the screening, diagnosis, and management of hyperglycemia and diabetes from these therapies. The need for such guidance is critical because diabetes management in the cancer patient is complex, individualized, and requires inter-disciplinary care. In the present narrative review, we synthesize and summarize the most relevant literature pertaining to diabetes and hyperglycemia in the setting of these cancer therapies and provide an updated patient-centered framework for their evaluation and management.

Treatment of Diabetes in Older Adults: An Endocrine Society* Clinical Practice Guideline.

OBJECTIVE: The objective is to formulate clinical practice guidelines for the treatment of diabetes in older adults. CONCLUSIONS: Diabetes, particularly type 2, is becoming more prevalent in the general population, especially in individuals over the age of 65 years. The underlying pathophysiology of the disease in these patients is exacerbated by the direct effects of aging on metabolic regulation. Similarly, aging effects interact with diabetes to accelerate the progression of many common diabetes complications. Each section in this guideline covers all aspects of the etiology and available evidence, primarily from controlled trials, on therapeutic options and outcomes in this population. The goal is to give guidance to practicing health care providers that will benefit patients with diabetes (both type 1 and type 2), paying particular attention to avoiding unnecessary and/or harmful adverse effects.

GLYCEMIC OUTCOMES 3 YEARS AFTER IMPLEMENTATION OF A PERI-OPERATIVE GLYCEMIC CONTROL ALGORITHM IN AN ACADEMIC INSTITUTION.

OBJECTIVE: While hyperglycemia in the postoperative setting has been linked to an increase in surgical complications, limited data are available to inform the management of patients with diabetes in the operating room and the immediate peri-operative period. We describe the results of a peri-operative glycemic control program that standardized intravenous insulin with a target glucose (BG) range of 120 to 180 mg/dL for patients with diabetes presenting with a BG level >180 mg/dL and included transition to subcutaneous insulin. METHODS: Patients with known diabetes and a BG >180 mg/dL who underwent surgery were included. The control group included 260 patients from March 2, 2008 through December 31, 2008. The intervention group included 588 patients following protocol implementation from April 1, 2009 through December 31, 2012. Data included demographic information, hospital BG values, length of stay (LOS), mortality, and wound infections. RESULTS: The intervention group had significantly lower BG on arrival in the postoperative care unit (182.2 vs 194.9 mg/dL, P = .012). Mean BG during the first 24 hours after surgery was lower in the intervention group (182.1 vs. 190.5 mg/dL), and there were fewer BG values >200 mg/dL in the intervention group (P = .005). The percentage of BG values <70 mg/dL during the hospital stay was lower in the intervention group (1.94 vs. 2.43%, P<.01). There was no significant difference in mortality, LOS, or wound infections. CONCLUSION: Following implementation of a hospital-wide peri-operative glycemic control algorithm, we found a reduction in peri-operative BG levels and hypoglycemia rates. Ongoing research is needed to assess the impact on clinical outcomes. ABBREVIATIONS: BG = blood glucose CCI = Charlson comorbidity index EHR = electronic health record ICD-9 = International Classification of Disease-9 IV = intravenous LOS = length of stay OR = operating room PACU = postoperative care unit POC = point-of-care.

Stress Hyperglycemia During Surgery and Anesthesia: Pathogenesis and Clinical Implications.

Numerous studies have demonstrated an association between hyperglycemia in the perioperative period and adverse clinical outcomes. Many patients who experience hyperglycemia while hospitalized do not have a known history of diabetes and experience a transient phenomenon often described as "stress hyperglycemia" (SH). We discuss the epidemiology and pathogenesis of SH as well as evidence to date regarding predisposing factors and outcomes. Further research is needed to identify the long-term sequelae of SH as well as perioperative measures that may modulate glucose elevations and optimal treatment strategies.

Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production.

OBJECTIVE: T cell inflammation plays pivotal roles in obesity-associated type 2 diabetes (T2DM). The identification of dominant sources of T cell inflammation in humans remains a significant gap in understanding disease pathogenesis. It was hypothesized that cytokine profiles from circulating T cells identify T cell subsets and T cell cytokines that define T2DM-associated inflammation. METHODS: Multiplex analyses were used to quantify T cell-associated cytokines in αCD3/αCD28-stimulated PBMCs, or B cell-depleted PBMCs, from subjects with T2DM or BMI-matched controls. Cytokine measurements were subjected to multivariate (principal component and partial least squares) analyses. Flow cytometry detected intracellular TNFα in multiple immune cell subsets in the presence/absence of antibodies that neutralize T cell cytokines. RESULTS: T cell cytokines were generally higher in T2DM samples, but Th17 cytokines are specifically important for classifying individuals correctly as T2DM. Multivariate analyses indicated that B cells support Th17 inflammation in T2DM but not control samples, while monocytes supported Th17 inflammation regardless of T2DM status. Partial least squares regression analysis indicated that both Th17 and Th1 cytokines impact %HbA1c. CONCLUSIONS: Among various T cell subsets, Th17 cells are major contributors to inflammation and hyperglycemia and are uniquely supported by B cells in obesity-associated T2DM.

Metformin may be associated with false-negative cancer detection in the gastrointestinal tract on PET/CT.

OBJECTIVE: Concurrent therapy with the antihyperglycemic drug metformin can hinder the detection of malignancy in the abdominal and pelvic portions of 18F-fluordeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging performed for the diagnosis or staging of malignancy, as well as for treatment response and radiation therapy planning. This is due to the metformin-induced increase in intestinal FDG radiotracer uptake. We aim to bring this potentially important interaction to the attention of clinicians who care for cancer patients with diabetes. METHODS: We searched MEDLINE (from 1970 to January 2014) and Google Scholar for relevant English-language articles using the following search terms: "metformin and FDG/PET, metformin and bowel uptake, metformin, and cancer, metformin and the intestine, metformin pharmacokinetics, hyperglycemia and FDG/PET." We reviewed the reference lists of pertinent articles with respect to metformin gut physiology, impact on FDG uptake and the effect on diagnostic accuracy of abdominalpelvic PET/CT scans with concurrent metformin therapy. RESULTS: We reviewed the action of metformin in the intestine, with particular emphasis on the role of metformin in PET/CT imaging and include a discussion of clinical studies on the topic to help refine knowledge and inform practice. Finally, we discuss aspects pertinent to the management of type 2 diabetes (T2D) patients on metformin undergoing PET/CT. CONCLUSIONS: Metformin leads to intense, diffusely increased FDG uptake in the colon, and to a lesser degree, the small intestine, which limits the diagnostic capabilities of FDG PET/CT scanning and may mask gastrointestinal malignancies. We suggest that metformin be discontinued 48 hours before FDG PET/CT scanning is performed in oncology patients. More rigorous data are needed to support the widespread generalizability of this recommendation.

Relevance of the Surgical Care Improvement Project on glycemic control in patients undergoing cardiac surgery who receive continuous insulin infusions.

OBJECTIVE: The Surgical Care Improvement Project (SCIP) has benchmarked 6:00 am blood glucose levels of less than 200 mg/dL on postoperative day (POD) 1 and 2 as quality measures of glycemic control in cardiac surgery. This study was undertaken to (1) determine the incidence of SCIP outliers in patients receiving a continuous insulin infusion (CII) targeted to maintain perioperative serum glucose levels less than 180 mg/dL after cardiac surgery, (2) identify the profile of patients who are SCIP outliers, (3) determine whether SCIP outliers have increased morbidity and mortality, and (4) identify more relevant benchmarks for glycemic control in patients having cardiac surgery. METHODS: Between January 1, 2008, and April 30, 2011, a total of 832 patients underwent cardiac surgery and received CII to maintain serum blood glucose levels of less than 180 mg/dL. Patients were divided into 2 groups: patients compliant with SCIP and SCIP outliers. RESULTS: The incidence of SCIP outliers was 6.6% (55/832). Patients more likely to be SCIP outliers had diabetes mellitus (38, 69% vs 250, 32%; P < .0001), a higher hemoglobin A1c (8.74 ± 2.25 vs 7.59 ± 2.90; P < .0009), and a higher body mass index (31.1 ± 6.5 vs 29.2 ± 5.7; P = .03). However, SCIP outliers had no increase in morbidity, mortality, or hospital length of stay. CONCLUSIONS: Patients undergoing cardiac surgery may still be SCIP outliers despite CII targeted to maintain serum glucose levels below 180 mg/dL; however, SCIP outliers had no increase in morbidity, mortality, or length of stay.

A primer for achieving glycemic control in the cardiac surgical patient.

Maintaining glycemic control (blood glucose <180 mg/dL) has been shown to reduce morbidity and enhance long-term survival in patients with diabetes mellitus following coronary artery bypass graft (CABG) surgery. In this review we present a management strategy to achieve perioperative glycemic control in all patients undergoing CABG surgery, with and without diabetes mellitus, designed to achieve compliance with current Surgical Care Improvement Project (SCIP) and Society of Thoracic Surgeons (STS) guidelines.

Creating a perioperative glycemic control program.

Hyperglycemia in the surgical population is a recognized risk factor for postoperative complications; however, there is little literature to date regarding the management of hyperglycemia in the perioperative period. Here, we detail the strategies that our institutions have employed to identify and treat hyperglycemia in patients with diabetes who present for surgery. Our approach focuses on the recognition of hyperglycemia and metabolic abnormalities, control of glucose levels via insulin infusion when needed, monitoring for hypoglycemia and a comprehensive multidisciplinary approach that provides standardized recommendations for patients at all points in care as they transition from the preoperative clinic into the operating room, and then into the hospital.

Inducible Toll-like receptor and NF-kappaB regulatory pathway expression in human adipose tissue.

OBJECTIVE: Inflammatory activity in fat tissue has recently been implicated in mechanisms of insulin resistance and obesity-related metabolic dysfunction. Toll-like receptors (TLRs) play a key role in innate immune responses and recent studies implicate the TLR pathway in mechanisms of inflammation and atherosclerosis. The aim of this study was to examine differential TLR expression and function in human adipose tissue. METHODS AND PROCEDURES: We biopsied subcutaneous abdominal fat from 16 obese subjects (age 39+/-11 years, BMI 49+/-14 kg/m2) and characterized TLR expression using quantitative real-time PCR and confocal immunofluorescence imaging. In tissue culture, we stimulated isolated human adipocytes with Pam3CSK4 and lipopolysaccharide (LPS) (TLR2 and TLR4 agonists, respectively) and quantified TLR activity, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) production, and nuclear factor-kappaB (NF-kappaB) p65 nuclear activation using real-time PCR, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. RESULTS: TLR1, 2, and 4 protein colocalized with adiponectin in human adipocytes with TLR4 exhibiting the highest immunohistochemical expression. Using real-time PCR, we confirmed higher level of gene expression for TLR4 as compared to other members of the TLR family (TLR1, 2, 7, 8) in human adipose depots (P<0.001). In tissue culture, adipocyte TLR2/TLR4 mRNA expression and protein increased significantly following Pam3CSK4 and LPS (P<0.001). TLR2/TLR4 stimulation was associated with NF-kappaB p65 nuclear translocation and proinflammatory cytokine production. DISCUSSION: The findings demonstrate that TLRs are inducible in adipose tissue and linked with downstream NF-kappaB activation and cytokine release. Adipose stores may play a dynamic role in the regulation of inflammation and innate immunity in human subjects via modulation of the TLR/NF-kappaB regulatory pathway.

An intracardiac accessory thyroid gland.

This report describes a 62-year-old woman with a history of pulmonary embolism who presented with a right ventricular cardiac mass that proved histologically to be normal thyroid tissue. The patient was clinically and biochemically euthyroid. Six months after excision, an iodine-123 whole-body uptake and scan demonstrated no residual ectopic thyroid tissue.