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ContextDiabetes 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.ObjectiveWe aimed to examine the associations between admission variables, including glycemic gap, and adverse clinical outcomes in patients hospitalized with COVID-19 infection.MethodsWe 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.ResultsThe 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).ConclusionRelative hyperglycemia, as measured by the admission glycemic gap, is an important marker of mortality risk in COVID-19.

To investigate whether diminishing insulin requirement in the third trimester is associated with placental dysfunction. Two-year retrospective cohort study at one tertiary care center of women with pregestational or gestational diabetes, their insulin requirements, and complications associated with placental dysfunction. Of 157 women, 21 (13%) experienced declining insulin requirement, with average decline of 28% at 34 weeks. They were more likely to have pregestational diabetes (71.4% vs. 42.6%; p

Objective: Diabetes mellitus is associated with poor outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Diabetic ketoacidosis (DKA) has also been reported to occur with this virus. A cluster of cases of euglycemic DKA (euDKA) was identified in patients with type 2 diabetes mellitus using sodium-glucose cotransporter-2 inhibitors (SGLT2is) who developed SARS-CoV-2 infection. Methods: The cases were identified by the authors while providing clinical care, and details were collected. Results: Five cases of euDKA, presenting with glucose levels

While diabetes and admission blood glucose (BG) are established risk factors for adverse outcomes during hospitalization for COVID-19, reports on the impact of prior glycemic control have been variable. We examined the relationship between acute and chronic glycemia on risk of ICU admission, mechanical ventilation (MV) , and mortality among 1,786 patients with diabetes or hyperglycemia (BG > 180 mg/dl twice during any 24-hr period during hospitalization) admitted from March 2020 to February 2021 with COVID-at 5 large university hospitals in the eastern U.S. The cohort was 51.3% male, 53.3% White, 18.8% Black, 29.3% Hispanic, with age = 64.8 ± 13.8 y, BMI = 31.5 ± 7.9 kg/m2, admission BG = 216 ± 134 mg/dl, and HbA1c = 8.1 ± 2.2%. During hospitalization, 38.9% were admitted to the ICU, 22.9% received MV, and 10.6% died. In multivariate regression analysis, among demographic factors, age was the strongest risk factor for in-hospital mortality (OR = 1.per year [95% CI: 1.04, 1.06]) , and Hispanic ethnicity was the greatest risk factor for ICU admission (OR = 1.45 [95% CI: 1.16, 1.80]) and intubation (OR = 1.64 [95% CI: 1.28, 2.10]) . Higher BMI (p = 0.005) and admission BG (p = 0.014) were associated with increased risk of mortality, but HbA1c was not. The glycemic gap (GG) , defined as admission BG minus estimated average BG based on HbA1c, was a stronger predictor of mortality than either admission BG or HbA1c alone. Mortality rate was 5.7% for GG < -20 mg/dl; 12.2% for GG = -20 to < 20 mg/dl; 12.4% for GG = 20 to < 100 mg/dl; and 16.1% for GG ≥ 100 mg/dl (p for trend < 0.001) . Conclusion: Among patients with diabetes or hyperglycemia admitted for COVID-19, in addition to previously established risk factors for poor outcomes (age, Hispanic ethnicity, and BMI) , we found that GG is a stronger predictor of in-hospital mortality than blood glucose alone. This suggests that relative hyperglycemia, as measured by the admission GG, is an important marker of disease severity in COVID-and potentially other serious illnesses. Disclosure M.E.Mcdonnell: Advisory Panel; Everlywell, Inc., Research Support; Lilly, Stock/Shareholder; Abbott Diabetes. G.P.Westcott: None. D.C.Simonson: Stock/Shareholder; GI Windows, Phase V Technologies, Inc. G.Gopalakrishnan: Research Support; Eli Lilly and Company, Spruce Biosciences. R.Garg: None. J.Mitri: Consultant; dairy management, Lnutra. R.S.Weinstock: Research Support; Boehringer Ingelheim International GmbH, Dexcom, Inc., Diasome, Eli Lilly and Company, Insulet Corporation, Kowa Pharmaceuticals America, Inc., Medtronic, Novo Nordisk, Tandem Diabetes Care, Inc., Tolerion, Inc. M.Greenfield: None. N.E.Palermo: Research Support; Dexcom, Inc. R.Radhakrishnan: None. Funding Brigham-TechFoundation, Cambridge, MA 2021

Looking for the Outsider A 44-year-old man presented with fatigue, unintentional weight loss, and a 2-year history of hip and chest-wall pain. He had earlier presented with acute right clavicle pai...

Context While individuals with diabetes appear to be at similar risk for SARS-CoV-2 infection to those without diabetes, they are more likely to suffer severe consequences, including death. Diabetic ketoacidosis (DKA) is a common and potentially lethal acute complication of diabetes arising from a relative insulin deficiency, which occurs more often in those with type 1 diabetes and in the setting of moderate to severe illness. Early reports indicate that among patients with pre-existing diabetes, DKA may be a common complication of severe COVID-19 and a poor prognostic sign. Case Description This clinical perspective explores the key elements of caring for individuals with DKA during the COVID-19 pandemic through 2 cases. Topics addressed include diagnosis, triage, and the fundamental principles of treatment with a focus on the importance of characterizing DKA severity and medical complexity to determine the best approach. Conclusions As discussed, some tenets of DKA management may require flexibility in the setting of COVID-19 due to important public health goals, such as preventing transmission to highest risk individuals, reducing healthcare worker exposure to infected patients, and preserving personal protective equipment. Evidence for alternative treatment strategies is explored, with special attention placed on treatment options that may be more relevant during the pandemic, including use of subcutaneous insulin therapy. Finally, DKA is often a preventable condition. We include evidence-based strategies and guidance designed to empower clinicians and patients to avoid this serious complication when possible.

People with diabetes (DM) hospitalized with COVID-19 infection have a 2-3 fold higher risk of death compared with those without DM, and mechanical ventilation (MV) has been identified as a major risk factor for death. While stress hyperglycemia (StH) has been established as a risk factor for death in some critically ill cohorts, it is not a well-established risk factor for MV in COVID-19. The COVIDEastDM consortium pooled data from 5 academic hospitals on the East Coast of the US to study the relationship between hyperglycemia and COVID-19 outcomes. Data were obtained retrospectively from electronic records of adults with COVID-19 and either DM or StH (defined in this cohort as day-1 admission blood glucose >180 mg/dl and A1c Disclosure M. E. Mcdonnell: Stock/Shareholder; Spouse/Partner; Abbott Diabetes. N. E. Palermo: None. R. Radhakrishnan: None. G. P. Westcott: None. R. S. Weinstock: Research Support; Self; Boehringer Ingelheim International GmbH, Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Kowa Research Institute, Inc., Medtronic, Tolerion, Inc. R. Garg: None. D. C. Simonson: Stock/Shareholder; Spouse/Partner; Phase V Technologies, Inc. G. Cromwell: None. G. Gopalakrishnan: None. M. Greenfield: None. M. Johnson: None. S. R. Katta: None. J. Lebastchi: None. J. Mitri: Consultant; Self; L-Nutra. Funding TechFoundation; Brigham Education Institute

Recent studies suggest COVID-19 infection has a detrimental effect on glycemic control in patients with diabetes in the acute care setting. However, there is limited information about the impact of COVID-19 on glycemic control in the months following infection. In this retrospective observational study, we examined the correlation between COVID-19 infection and glycemic control in adult patients with elevated A1c in a single health system (n=3,295). Patients were selected from a cohort of those age 18 years or older who were tested for COVID-19 between 3/1/2020 and 11/1/2020. COVID positive patients were identified through positive SARS-CoV-2 PCR or a COVID flag in the EMR. COVID negative patients were randomly selected in a 3:1 ratio from all patients who had a negative COVID test in the same week as each positive patient. Patients from this cohort were included if they had a baseline A1c ≥ 5.7% measured in the preceding six months and at least two weeks prior to their COVID positive (n=670) or COVID negative (n=2,625) test date, as well as an endpoint A1c ≥ 5.7% at least three months after this date. The study population was 54% female, 60% White, 20% Hispanic, and 13% Black with a mean BMI 32 ± 7.3 kg/m2, age 64.1 ± 13.6 yrs, and baseline A1c of 7.7± 1.6 %; 81% of patients had a diagnosis of type 2 diabetes. In a linear regression model, COVID-19 infection was significantly associated with increased endpoint A1c (coefficient = 0.14, 95% CI [0.03 - 0.25], p = 0.01). Baseline A1c, male sex, and Hispanic ethnicity were also significantly associated with increased A1c, while age and median income based on zip code were associated with decreased A1c. In conclusion, prior COVID-19 infection appears to be associated with worse glycemic control at least 3 months post-infection compared to patients who did not contract COVID-19. Additional research is needed to determine if this association is present in other patient populations as well as the physiologic and socio-demographic causes for this finding. Disclosure E. G. Thurber: None. M. E. Mcdonnell: Stock/Shareholder; Spouse/Partner; Abbott Diabetes. G. Cromwell: None. M. Johnson: None. D. C. Simonson: Stock/Shareholder; Spouse/Partner; Phase V Technologies, Inc. N. E. Palermo: None.

This article is the work product of the Continuous Glucose Monitor and Automated Insulin Dosing Systems in the Hospital Consensus Guideline Panel, which was organized by Diabetes Technology Society and met virtually on April 23, 2020. The guideline panel consisted of 24 international experts in the use of continuous glucose monitors (CGMs) and automated insulin dosing (AID) systems representing adult endocrinology, pediatric endocrinology, obstetrics and gynecology, advanced practice nursing, diabetes care and education, clinical chemistry, bioengineering, and product liability law. The panelists reviewed the medical literature pertaining to five topics: (1) continuation of home CGMs after hospitalization, (2) initiation of CGMs in the hospital, (3) continuation of AID systems in the hospital, (4) logistics and hands-on care of hospitalized patients using CGMs and AID systems, and (5) data management of CGMs and AID systems in the hospital. The panelists then developed three types of recommendations for each topic, including clinical practice (to use the technology optimally), research (to improve the safety and effectiveness of the technology), and hospital policies (to build an environment for facilitating use of these devices) for each of the five topics. The panelists voted on 78 proposed recommendations. Based on the panel vote, 77 recommendations were classified as either strong or mild. One recommendation failed to reach consensus. Additional research is needed on CGMs and AID systems in the hospital setting regarding device accuracy, practices for deployment, data management, and achievable outcomes. This guideline is intended to support these technologies for the management of hospitalized patients with diabetes.

Recent data shows significant cardiovascular and renal benefit due to SGLT2 inhibitor (SGLT2i) therapy. However, use in the acute setting is limited and deferred due to concern of ketoacidosis especially in the setting of decreased nutrition intake and illness. Between 5/1/19 and 11/25/19 in one hospital, the inpatient formulary allowed the use of SGLT2i in patients with diabetes on the cardiology service as part of a supervised pilot program. As a result, 94 hospitalized patients were exposed to at least one dose of SGLT2i, 24 (25%) directed by the pilot program (PILOT), and 70 (75%) undirected (UND). In the UND group, 12 (13%) were newly started on SGLT2i and 58 (62%) were continued from home. Among all patients, 29.8 % were women, mean age 65, A1c 8.3% and GFR 67 mL/min. 17 patients (18%) had GFR ≤ 45, who were 5 years older on average (p= 0.04). In hospital there was no incident metabolic acidosis or clinically significant hypoglycemia. 79.8% of patients remained on SGLT2i at 1 month. 55 patients had data within 3 months post discharge. Of those still taking SGLT2i at 1 month, there was no significant change in systolic BP (SBP) at 1 or 3 months across all groups. In the UND group, there was no significant change in GFR. By comparison, in the PILOT group there was both a significant decrease in estimated GFR at 1 month (-6.95 mL/min, p= In conclusion, permitting use of SGLT2i in the acute setting to select populations is likely to increase overall exposure of the drug to the general inpatient diabetes population. While we did not identify ketoacidosis, which is rare, reduction in GFR is common. Substantial education and direction is needed for inpatient clinicians in both the inadvertent and intended use of SGLT2is. Disclosure N.E. Palermo: None. M. Goodberlet: None. G. Cromwell: None. C.M. Smith: None. A. Bilodeau: None. P.M. Szumita: None. M.E. McDonnell: None.

Recent data have shown significant benefit from SGLT2 inhibitors (SGLT2i) in patients with diabetes (DM) and cardiovascular disease (CVD) but experience with use in the acute care setting is limited and feasibility of initiating in the hospital is unclear. A multidisciplinary team of cardiology, endocrinology, and pharmacy developed a pilot to assess the feasibility of initiating SGLT2i in the hospital and subsequent transition of care. From 5/4/19 to 10/6/19, patients with DM on the cardiology service were identified and initiated on therapy with an SGLT2i if there were no contraindications. All patients were offered education via fact sheet, video, and/or focused consultation from the inpatient diabetes team. All prescriptions were either filled or verified as covered by insurance prior to discharge. An electronic communication was sent to notify the PCP and recommend basic metabolic labs be done at 2 weeks after initiation. 24 patients were eligible and 23 (96%) filled the prescription at discharge. 54.2% had CAD while 75% had CHF: 45.8% HFrEF and 29.2% HFpEF. The median GFR was 54 mL/min (44-64) and mean A1c was 8.1%. At 1 month, 71% remained on SGLT2i (n=17) and 63% completed recommended labs (n=15). 79% had outpatient follow up by 30 days (N=24) and 91% by 90 days (N=12). One patient died of respiratory failure within 30 days. 33% were readmitted within 90 days due to non-CHF cardiac illness (50%), respiratory problem (25%), lightheadedness (13%, n=1), or urinary tract infection (13%, n=1), and none for diabetes or CHF. There were no cases of metabolic acidosis or electrolyte disturbance. There was both a significant decrease in estimated GFR at 1 month (-6.95 mL/min, p= 30% reduced GFR and 1 advanced from CKD stage 4 to 5. In conclusion, initiation of SGLT2i therapy in select patients with CVD and DM in the acute care setting appears to be feasible. Guidance is needed to ensure appropriate patient selection and medication adjustment in these patients. Disclosure N.E. Palermo: None. M. Goodberlet: None. G. Cromwell: None. C.M. Smith: None. L. Chang: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Other Relationship; Self; Applied Therapeutics, Fractyl Laboratories, Inc., Novo Nordisk Inc., Sanofi. A. Bilodeau: None. J. Plutzky: Consultant; Self; Amgen, AstraZeneca, Janssen Pharmaceuticals, Inc., Novo Nordisk A/S. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. P.M. Szumita: None. O. Hulme: None. C. Cannon: None. M.E. McDonnell: None.

PURPOSE OF REVIEW: To assess evidence to date for use of non-insulin agents in treatment of gestational diabetes mellitus. RECENT FINDINGS: There has been increasing interest in the use of non-insulin agents, primarily metformin and glyburide (which both cross the placenta). Metformin has been associated with less maternal weight gain; however, recent studies have shown a trend toward increased weight in offspring exposed to metformin in utero. Glyburide has been associated with increased neonatal hypoglycemia. SUMMARY: Glycemic control during pregnancy is essential to optimize both maternal and fetal outcomes. There are a myriad of factors to consider when designing treatment programs including patient preference, phenotype, and glucose patterns. While insulin is typically recommended as first-line, some women refuse or cannot afford insulin and in those cases, non-insulin agents may be used. Further studies are needed to assess treatment in pregnancy, perinatal outcomes, and particularly long-term metabolic profiles in mothers and offspring.

Silicone/mineral oil‐induced granulomas have been described as an inflammatory granulomatous response when silicone/mineral oil is injected for cosmetic purposes. These sclerosing granulomas can lead to hypercalcemia. Here we present a 33‐year‐old man with hypercalcemia, hypophosphatemia, progressively worsening fatigue, severe proximal muscle weakness, and depression. He had an athletic build with increased muscle bulk and several areas of indurated, nontender, firm, well‐circumscribed lesions in the subcutaneous tissue of his anterior pectoralis, triceps, and biceps bilaterally because of injecting himself with silicone/mineral oil‐based product into his muscles. Sclerosing granulomas were diagnosed on the MRI. He had extremely low or undetectable serum levels of 25‐hydroxyvitamin D [25(OH)D], and persistently elevated serum levels of 1,25‐dihydroxyvitamin D [1,25(OH)2D] and calcium. He developed hypophosphatemia associated with elevated levels of fibroblast growth factor 23 (FGF‐23) and severe proximal muscle weakness. Treatment with systemic steroids, furosemide, calcitonin, ketoconazole, and denosumab resulted in a significant decrease in his serum calcium, but with minimal impact on his hypophosphatemia and fatigue.Correcting his severe vitamin D deficiency with small doses of vitamin D and raising his blood level of 25(OH)D from undetectable to 10 ng/mL without significantly affecting his serum calcium or phosphate was effective in reversing his severe proximal muscle weakness, permitting him to lift his head and to be free of his wheelchair. Although measurement of the 1,25(OH)2D level is not mandatory in all cases of hypercalcemia, it is indicated in a patient who has low serum PTH levels. Clinicians need to be aware that vitamin D deficiency can cause severe proximal muscle weakness such that the patient is unable to lift his head from his chest or ambulate. This may lead to a psychiatric disorder misdiagnosis. © 2019 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Several studies have demonstrated the benefits of glycemic control in the perioperative period and there is ongoing interest in development of systematic approaches to achieving glycemic control. This review discusses currently available data and proposes a new approach to the management of hyperglycemia in the perioperative period. In a recent study, we demonstrated that early preoperative identification of patients with poorly controlled diabetes and proactive treatment through various phases of surgery improves glycemic control, lowers the risk of surgical complications, and decreases the length of hospital stay. Implementation of a perioperative diabetes program that systematically identifies and treats patients with poor glycemic control early in the preoperative period is feasible and improves clinical care of patients undergoing elective surgery.

Objective: Patients who present to the emergency department (ED) for diabetes without hyperglycemic crisis are at risk of unnecessary hospitalizations and poor outcomes. To address this, the ED Diabetes Rapid-referral Program (EDRP) was designed to provide ED staff with direct booking into the diabetes center. The objective of this study was to determine the effects of the EDRP on hospitalization rate, ED utilization rate, glycemic control, and expenditures. Methods: We conducted a single-center analysis of the EDRP cohort (n = 420) and compared 1-year outcomes to historic controls (n = 791). We also compared EDRP patients who arrived (ARR) to those who did not show (NS). The primary outcome was hospitalization rate over 1 year. Secondary outcomes included ED recidivism rate, hemoglobin A1c (HbA1c), and healthcare expenditures. Results: Compared with controls, the EDRP cohort was less likely to be hospitalized (27.1% vs. 41.5%, P

The patterns of emergency department (ED) visits in patients with diabetes are not well understood. The Emergency Department Diabetes Rapid-referral Program (EDRP) allows direct booking of ED patients presenting with urgent diabetes needs into a diabetes specialty clinic within 1 day of ED discharge. The objective of this secondary analysis was to examine characteristics of patients with diabetes who have frequent ED visits and determine reasons for revisits.A single-center analysis was conducted comparing patients referred to the EDRP (n = 420) to historical unexposed controls (n = 791). The primary outcome was the proportion of patients in each frequency group of ED revisits (none, 1 to 3 [infrequent], 4 to 10 [frequent], or10 [superfrequent]) in the year after the ED index visit. Secondary outcomes were hospitalization rates and International Classification of Diseases-Ninth Revision (ICD-9) diagnoses at ED revisits.Superfrequent users, responsible for20% of total ED visits, made up small but not significantly different proportions of EDRP and control populations, 3.6% and 5.2%, respectively. Superfrequent groups had lower hospital admission rates at ED revisits compared to frequent groups. Mental health disorders (including substance abuse) were the primary, secondary, or tertiary ICD-9 codes in 30.6% (95% confidence interval [CI], 27.7% to 33.5%) and 6.6% (95% CI, 5.1% to 8.2%) in the superfrequent and infrequent groups, respectively.Direct access to diabetes specialty care from the ED is effective in reducing ED recidivism but not amongst a small subgroup of superfrequent ED users. This group was more likely to have mental health disorders recorded at ED revisits, suggesting that more comprehensive approaches are needed for this population.EDRP = Emergency Department Diabetes Rapid-referral Program; ED = emergency department; HbA1c = hemoglobin A1c; ICD-9 = International Classification of Diseases-Ninth Revision.

Purpose of review Nelson's syndrome is a rare complication that can occur during the course of management of Cushing's disease. This article summarizes the recent literature on the diagnosis, monitoring and treatment of this potentially life-threatening outcome. Recent findings Nelson's syndrome, with rising adrenocorticotropin hormone levels and corticotroph tumor progression on diagnostic imaging, can develop following treatment of refractory Cushing's disease with total bilateral adrenalectomy with/without radiotherapy. However, data showing that radiotherapy prevents Nelson's syndrome is inconsistent. In addition to the treatment of Nelson's syndrome with neurosurgery with/without adjuvant radiotherapy, selective somatostatin analogs and dopamine agonists, as well as other novel agents, have been used with increasing frequency in treating cases of Nelson's syndrome with limited benefit. The risk-benefit profile of each of these therapies is still not completely understood. Summary Consensus guidelines on the evaluation and management of Nelson's syndrome are lacking. This article highlights areas in the surveillance of Cushing's disease patients, and diagnostic criteria and treatment regimens for Nelson's syndrome that require further research and review by experts in the field.

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.

Some of the clinically significant causes of vitamin D deficiency in children are secondary to inadequate dietary intake, limited sun exposure, disease states causing malabsorption (celiac disease, gastric and small bowel resection, pancreatic insufficiency from cystic fibrosis) and altered metabolism secondary to medications. In utero and during childhood vitamin D deficiency can have a myriad of health consequences extending beyond musculoskeletal health to acute and chronic disease. In this review, it discusses the prevalence of vitamin D deficiency, clinical spectrum of disease presentations in children with emphasis in children with disabilities, vitamin D's role in bone and nonskeletal heath as well as recommendations for prevention and treatment of vitamin D deficiency.