Perioperative Management of Diabetes Mellitus: Novel Approaches.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.

The Use of Non-insulin Agents in Gestational Diabetes: Clinical Considerations in Tailoring Therapy.

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. 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.

REDUCED IMPACT OF DIABETES CLINIC REFERRAL ON HIGH-FREQUENCY EMERGENCY DEPARTMENT USERS.

OBJECTIVE: 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. METHODS: 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], or >10 [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. RESULTS: Superfrequent users, responsible for >20% 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. CONCLUSION: 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. ABBREVIATIONS: EDRP = Emergency Department Diabetes Rapid-referral Program; ED = emergency department; HbA1c = hemoglobin A1c; ICD-9 = International Classification of Diseases-Ninth Revision.

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.

OPEN ACCESS TO DIABETES CENTER FROM THE EMERGENCY DEPARTMENT REDUCES HOSPITALIZATIONS IN THE SUSEQUENT YEAR.

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<.001) or return to the ED (52.2% vs. 62.3%, P = .001) at the end of 1 year. Total hospitalizations were also lower in the EDRP (157 ± 19 vs. 267 ± 18 per 1,000 persons per year, P<.001). The EDRP cohort had a greater reduction in HbA1c (-2.66 vs. -2.01%, P<.001), which was more pronounced when ARR patients were compared with NS (-2.71% vs. -1.37%, P<.05). The mean per patient institutional healthcare expenditures were lower by $5,461 compared with controls. CONCLUSION: Eliminating barriers to scheduling diabetes-focused ambulatory care for ED patients was associated with significant reductions in hospitalization rate, ED recidivism rate, HbA1c, and healthcare expenditures in the subsequent year. ABBREVIATIONS: ARR = arrived ED = emergency department EDRP = emergency department diabetes rapid-referral Program HbA1c = hemoglobin A1c NS = no show.

Predictors of readmission and mortality in adults with diabetes or stress hyperglycemia after initial hospitalization for COVID-19.

INTRODUCTION: We previously reported predictors of mortality in 1786 adults with diabetes or stress hyperglycemia (glucose>180 mg/dL twice in 24 hours) admitted with COVID-19 from March 2020 to February 2021 to five university hospitals. Here, we examine predictors of readmission. RESEARCH DESIGN AND METHODS: Data were collected locally through retrospective reviews of electronic medical records from 1786 adults with diabetes or stress hyperglycemia who had a hemoglobin A1c (HbA1c) test on initial admission with COVID-19 infection or within 3 months prior to initial admission. Data were entered into a Research Electronic Data Capture (REDCap) web-based repository, and de-identified. Descriptive data are shown as mean±SD, per cent (%) or median (IQR). Student's t-test was used for comparing continuous variables with normal distribution and Mann-Whitney U test was used for data not normally distributed. X2 test was used for categorical variable. RESULTS: Of 1502 patients who were alive after initial hospitalization, 19.4% were readmitted; 90.3% within 30 days (median (IQR) 4 (0-14) days). Older age, lower estimated glomerular filtration rate (eGFR), comorbidities, intensive care unit (ICU) admission, mechanical ventilation, diabetic ketoacidosis (DKA), and longer length of stay (LOS) during the initial hospitalization were associated with readmission. Higher HbA1c, glycemic gap, or body mass index (BMI) were not associated with readmission. Mortality during readmission was 8.0% (n=23). Those who died were older than those who survived (74.9±9.5 vs 65.2±14.4 years, p=0.002) and more likely had DKA during the first hospitalization (p<0.001). Shorter LOS during the initial admission was associated with ICU stay during readmission, suggesting that a subset of patients may have been initially discharged prematurely. CONCLUSIONS: Understanding predictors of readmission after initial hospitalization for COVID-19, including older age, lower eGFR, comorbidities, ICU admission, mechanical ventilation, statin use and DKA but not HbA1c, glycemic gap or BMI, can help guide treatment approaches and future research in adults with diabetes.

Diabetes Mellitus Type 1 Presenting in the Setting of Diabetic Ketoacidosis and Acute SARS-CoV-2 Infection in Pregnancy.

Background/Objective: Diabetic ketoacidosis (DKA) during pregnancy is an obstetric emergency associated with a higher rate of maternofetal morbidity and mortality. Pregnancy itself is a ketosis-prone state and several unique mechanisms predispose to the development of insulin resistance, which can be further exacerbated by acute stressors such as infection. Thus, pregnant patients who additionally contract COVID-19 may be at an even higher risk of development of DKA. Case Report: A 32-year-old patient, with no prior history of impaired glucose tolerance, presented at 27 weeks of gestation with a 3-day history of shortness of breath, congestion, loss of taste and smell, polyuria, and polydipsia. Biochemical evaluation was consistent with DKA. Subsequently, she was diagnosed with acute SARS-CoV-2 infection. Treatment included intravenous hydration, electrolyte replacement, and insulin infusion. Postpartum phenotypic evaluation confirmed autoimmune diabetes (positive GAD-65 and zinc T8 antibodies) with residual ß-cell function. Six months postpartum, glycemic control remains at goal with basal- bolus insulin regimen. Discussion: This case describes the peculiar ability of SARS-CoV-2 infection to potentially rouse autoimmunity and how COVID-19 and DKA in pregnancy can be particularly challenging given the risk of significant maternal and fetal morbidity and mortality. Conclusion: Prompt diagnosis and evaluation of DKA in pregnancy as well as a higher level of suspicion is needed in the setting of SARS-CoV-2 infection. Additionally, this case depicts the need for closely monitoring the postpartum period for patients at risk of autoimmune disease, which may have been blunted in pregnancy.

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.

Euglycemic Diabetic Ketoacidosis With COVID-19 Infection in Patients With Type 2 Diabetes Taking SGLT2 Inhibitors.

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 <300 mg/dL, were identified over the course of 2 months by the endocrinology consult service. All patients had a history of type 2 diabetes mellitus with no known history of DKA. All were taking SGLT2is. Oral antihyperglycemic medications were stopped for all patients on admission. All received intravenous insulin infusion to treat DKA before being transitioned to a subcutaneous insulin regimen. SGLT2i use was discontinued for all patients who were discharged. CONCLUSION: EuDKA has been seen in the setting of acute illness in patients using SGLT2is, but this cluster of cases suggests that there is a specific association with SARS-CoV-2 infection. In addition to the known risk of euDKA with SGLT2i use, coronavirus disease 2019-specific mechanisms may include a direct toxic effect of the virus on the pancreatic islets, an accelerated inflammatory response promoting ketosis, and the diuretic effect of SGLT2i in conjunction with anorexia and vomiting. It is crucial to counsel patients to stop SGLT2is when sick, especially if SARS-CoV-2 infection is suspected.

Diabetic Ketoacidosis in COVID-19: Unique Concerns and Considerations.

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.

Continuous Glucose Monitors and Automated Insulin Dosing Systems in the Hospital Consensus Guideline.

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.

Man of Steel Syndrome: Silicone and Mineral Oil Injections With Associated Hypercalcemia, Hypophosphatemia, and Proximal Muscle Weakness.

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.

Re-examining Nelson's syndrome.

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.

Vitamin D, bone health, and other health benefits in pediatric patients.

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.