Glycemic Gap Predicts Mortality in a Large Multicenter Cohort Hospitalized With COVID-19.

CONTEXT: Diabetes or hyperglycemia at admission are established risk factors for adverse outcomes during hospitalization for COVID-19, but the impact of prior glycemic control is not clear. OBJECTIVE: We aimed to examine the associations between admission variables, including glycemic gap, and adverse clinical outcomes in patients hospitalized with COVID-19 infection. METHODS: We examined the relationship between clinical predictors, including acute and chronic glycemia, and clinical outcomes, including intensive care unit (ICU) admission, mechanical ventilation (MV), and mortality among 1786 individuals with diabetes or hyperglycemia (glucose > 10 mmol/L twice in 24 hours) who were admitted from March 2020 through February 2021 with COVID-19 infection at 5 university hospitals in the eastern United States. RESULTS: The cohort was 51.3% male, 53.3% White, 18.8% Black, 29.0% Hispanic, with age = 65.6 ± 14.4 years, BMI = 31.5 ± 7.9 kg/m2, glucose = 12.0 ± 7.5 mmol/L [216 ± 135 mg/dL], and HbA1c = 8.07% ± 2.25%. During hospitalization, 38.9% were admitted to the ICU, 22.9% received MV, and 10.6% died. Age (P < 0.001) and admission glucose (P = 0.014) but not HbA1c were associated with increased risk of mortality. Glycemic gap, defined as admission glucose minus estimated average glucose based on HbA1c, was a stronger predictor of mortality than either admission glucose or HbA1c alone (OR = 1.040 [95% CI: 1.019, 1.061] per mmol/L, P < 0.001). In an adjusted multivariable model, glycemic gap, age, BMI, and diabetic ketoacidosis on admission were associated with increased mortality, while higher estimated glomerular filtration rate (eGFR) and use of any diabetes medication were associated with lower mortality (P < 0.001). CONCLUSION: Relative hyperglycemia, as measured by the admission glycemic gap, is an important marker of mortality risk in COVID-19.

Medicaid insured persons with diabetes have increased proportion of missed appointments and high HbA1c.

Objective: This study was conducted to evaluate whether the type of insurance coverage is associated with missed appointments and to evaluate the effect of missed appointments on diabetes control. Methods: All patients with diabetes mellitus (DM) managed at a major academic medical center between Jan 2015 and Dec 2020 were included in analysis. Association between insurance coverage and the proportion of missed appointments was evaluated with adjustments for demographic variables and social determinants of health. The relationship between proportion of missed appointments and glycemic control was also evaluated. Results: The dataset included 30,633 patients, out of which 14,064 (46%) reported commercial insurance, 13,376 (44%) reported Medicare and 3,193 (10%) reported Medicaid coverage. Proportion of missed appointments was 18.1 ± 18.1% among Medicaid covered patients,12.1 ± 15.3% among commercially insured and 10.2 ± 14.1% among Medicare covered patients (p < 0.001). Type of insurance was found to be a significant predictor of proportion of missed appointments after adjusting for age, race, language, marital status, smoking, BMI, HbA1c and type of diabetes (p < 0.001) in series regression analysis. Proportion of missed appointments was associated with HbA1c with partial correlation coefficient +0.104 (p < 0.005) after adjusting for age, race, gender, type of insurance coverage, BMI and type of diabetes. Conclusions: Medicaid covered patients with diabetes have higher proportion of missed clinic appointments and higher HbA1c. More research is needed to evaluate the root causes of inability to keep appointments in this population so that strategies for improved healthcare delivery can be designed.

The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development.

Many inflammation-associated diseases, including cancers, increase in women after menopause and with obesity. In contrast to anti-inflammatory actions of 17ß-estradiol, we find estrone, which dominates after menopause, is pro-inflammatory. In human mammary adipocytes, cytokine expression increases with obesity, menopause, and cancer. Adipocyte:cancer cell interaction stimulates estrone- and NFκB-dependent pro-inflammatory cytokine upregulation. Estrone- and 17ß-estradiol-driven transcriptomes differ. Estrone:ERα stimulates NFκB-mediated cytokine gene induction; 17ß-estradiol opposes this. In obese mice, estrone increases and 17ß-estradiol relieves inflammation. Estrone drives more rapid ER+ breast cancer growth in vivo. HSD17B14, which converts 17ß-estradiol to estrone, associates with poor ER+ breast cancer outcome. Estrone and HSD17B14 upregulate inflammation, ALDH1 activity, and tumorspheres, while 17ß-estradiol and HSD17B14 knockdown oppose these. Finally, a high intratumor estrone:17ß-estradiol ratio increases tumor-initiating stem cells and ER+ cancer growth in vivo. These findings help explain why postmenopausal ER+ breast cancer increases with obesity, and offer new strategies for prevention and therapy.

Diagnosis and management of renal dysfunction in patients with cirrhosis.

Introduction: Renal dysfunction commonly occurs in patients with cirrhosis and is typically associated with poor prognosis. Several pathophysiologic mechanisms are responsible for renal disease in these patients, prompt identification permits individualized management.Areas covered: Pathophysiology, evaluation and differential diagnosis, management and prognosis of renal disease in patients with cirrhosis. Special focus on management of hepatorenal syndrome and indications for simultaneous liver-kidney transplantation.Literature search methodology: a detailed literature search was performed using PubMed without date restrictions. Published guidelines and position papers were also used and cross-referenced to identify additional studies.Expert opinion: The prognostic significance of renal dysfunction in patients with cirrhosis is highlighted by the inclusion of serum creatinine in the model for end-stage liver disease (MELD). Both acute and chronic renal dysfunction result in increased mortality in patients with cirrhosis, although there are marked differences related to the etiology of renal disease. Early recognition and prompt intervention determined by the most likely etiology are key in the management of these patients. Simultaneous liver-kidney transplantation improves patient survival compared to isolated liver transplantation in patients with cirrhosis and persistent renal impairment; however, selection of candidates must be judicious and individualized due to the ongoing shortage of donor kidneys.