Severe hyperglycemia and insulin resistance in patients with SARS-CoV-2 infection: a report of two cases.

BACKGROUND: Severe insulin resistance is an uncommon finding in patients with type 2 diabetes but is often associated with difficult to managing blood glucose. While severe insulin resistance is most frequently seen in the setting of medication side effects or rare genetic conditions, this report of two cases highlights the presence of severe insulin resistance in the setting of severe COVID-19 and explores how this may contribute to the poor prognosis of patients with diabetes who become infected with SARS-CoV-2. CASE PRESENTATION: Here we present the cases of two African-American women with pre-existing type 2 diabetes who developed severe COVID-19 requiring mechanical ventilation and concurrent severe insulin resistance with total daily insulin dose requirements of greater than 5 unit/kg. Both patients received aggressive insulin infusion and subcutaneous insulin therapy to obtain adequate glucose management. As their COVID-19 clinical course improved, their severe insulin resistance improved as well. CONCLUSIONS: The association between critical illness and hyperglycemia is well documented in the literature, however severe insulin resistance is not commonly identified and may represent a unique clinical feature of the interaction between SARS-CoV-2 infection and type 2 diabetes.

An Emergency Department-Based Intensive Care Unit is Associated with Decreased Hospital and Intensive Care Unit Utilization for Diabetic Ketoacidosis.

BACKGROUND: Many emergency department (ED) patients in diabetic ketoacidosis (DKA) are admitted to an inpatient intensive care unit (ICU), while ICU capacity is under increasing strain. The Emergency Critical Care Center (EC3), a hybrid ED-ICU setting, opened with the goal of providing rapid initiation of ICU care in the ED. OBJECTIVE: We sought to evaluate the impact of an ED-ICU on disposition and safety outcomes for adult ED patients in DKA. METHODS: This was a retrospective pre-post cohort of ED visits from 2012-2018 at a single academic medical center. Adult ED patients in DKA (pH < 7.30, HCO3 < 18 mEq/L, anion gap > 14, and glucose > 250 mg/dL) immediately before (pre-EC3) and after (post-EC3) opening of an ED-ICU were identified. ED disposition and safety data were collected and analyzed. RESULTS: We identified 631 patient encounters: 217 pre-EC3 and 414 post-EC3. Baseline demographics were similar between cohorts. Fewer patients in the post-EC3 cohort were admitted to an ICU (11.6% vs. 23.5%, p < 0.001, number needed to treat [NNT] = 8) or general floor bed (58.0% vs. 73.3%, p < 0.001, NNT = 6), and more were discharged from the ED (27.1% vs. 1.4%, p < 0.001, NNT = 4). Rates of hypokalemia (10.1% vs. 6.0%, p = 0.08) and admission to non-ICU with transfer to ICU within 24 h (0.5% vs. 0%, p = 0.30) did not differ. CONCLUSION: Management of patients with DKA in an ED-ICU was associated with decreased ICU and hospital utilization with similar safety outcomes. Managing rapidly reversible critical illnesses in an ED-ICU may help obviate increasing strain facing many health care systems.

THE EFFICACY AND SAFETY OF CO-ADMINISTRATION OF SITAGLIPTIN WITH METFORMIN IN PATIENTS WITH TYPE 2 DIABETES AT HOSPITAL DISCHARGE.

OBJECTIVE: Few randomized controlled trials have focused on the optimal management of patients with type 2 diabetes (T2D) during the transition from the inpatient to outpatient setting. This multicenter open-label study explored a discharge strategy based on admission hemoglobin A1c (HbA1c) to guide therapy in general medicine and surgery patients with T2D. METHODS: Patients with HbA1c ≤7% (53 mmol/mol) were discharged on sitagliptin and metformin; patients with HbA1c between 7 and 9% (53-75 mmol/mol) and those >9% (75 mmol/mol) were discharged on sitagliptinmetformin with glargine U-100 at 50% or 80% of the hospital daily dose. The primary outcome was change in HbA1c at 3 and 6 months after discharge. RESULTS: Mean HbA1c on admission for the entire cohort (N = 253) was 8.70 ± 2.3% and decreased to 7.30 ± 1.5% and 7.30 ± 1.7% at 3 and 6 months ( P<.001). Patients with HbA1c <7% went from 6.3 ± 0.5% to 6.3 ± 0.80% and 6.2 ± 1.0% at 3 and 6 months. Patients with HbA1c between 7 and 9% had a reduction from 8.0 ± 0.6% to 7.3 ± 1.1% and 7.3 ± 1.3%, and those with HbA1c >9% from 11.3 ± 1.7% to 8.0 ± 1.8% and 8.0 ± 2.0% at 3 and 6 months after discharge (both P<.001). Clinically significant hypoglycemia (<54 mg/dL) was observed in 4%, 4%, and 7% among patients with a HbA1c <7%, 7 to 9%, and >9%, while a glucose <40 mg/dL was reported in <1% in all groups. CONCLUSION: The proposed HbA1c-based hospital discharge algorithm using a combination of sitagliptin-metformin was safe and significantly improved glycemic control after hospital discharge in general medicine and surgery patients with T2D. ABBREVIATIONS: BG = blood glucose; DPP-4 = dipeptidyl peptidase-4; eGFR = estimated glomerular filtration rate; HbA1c = hemoglobin A1c; T2D = type 2 diabetes.

The Two-Bag Method for Treatment of Diabetic Ketoacidosis in Adults.

BACKGROUND: The "two-bag method" of management of diabetic ketoacidosis (DKA) allows for titration of dextrose delivery by adjusting the infusions of two i.v. fluid bags of varying dextrose concentrations while keeping fluid, electrolyte, and insulin infusion rates constant. OBJECTIVE: We aimed to evaluate the feasibility and potential benefits of this strategy in adult emergency department (ED) patients with DKA. METHODS: This is a before-and-after comparison of a protocol using the two-bag method operationalized in our adult ED in 2015. A retrospective electronic medical record search identified adult ED patients presenting with DKA from January 1, 2013 to June 30, 2016. Clinical and laboratory data, timing of medical therapies, and safety outcomes were collected and analyzed. RESULTS: Sixty-eight patients managed with the two-bag method (2B) and 107 patients managed with the one-bag method (1B) were identified. The 2B and 1B groups were similar in demographics and baseline metabolic derangements, though significantly more patients in the 2B group received care in a hybrid ED and intensive care unit setting (94.1% vs. 51.4%; p < 0.01). 2B patients experienced a shorter interval to first serum bicarbonate ≥ 18 mEq/L (13.4 vs. 20.0 h; p < 0.05), shorter duration of insulin infusion (14.1 vs. 21.8 h; p < 0.05), and fewer fluid bags were charged to the patient (5.2 vs. 29.7; p < 0.01). Frequency of any measured hypoglycemia or hypokalemia trended in favor of the 2B group (2.9% vs. 10.3%; p = 0.07; 16.2% vs. 27.1%; p = 0.09; respectively), though did not reach significance. CONCLUSIONS: The 2B method appears feasible for management of adult ED patients with DKA, and use was associated with earlier correction of acidosis, earlier discontinuation of insulin infusion, and fewer i.v. fluid bags charged than traditional 1B methods, while no safety concerns were observed.

Hypoglycemia in Hospitalized Hemodialysis Patients With Diabetes: An Observational Study.

INTRODUCTION: Hypoglycemia and hyperglycemia affect outcomes in hospitalized patient. Patients with diabetes and end stage renal disease are prone to hypoglycemia and few studies have evaluated glucometrics to identify the incidence and risk factors for hypoglycemia in this population. METHODS: We designed an observational retrospective review of 150 insulin requiring inpatients with diabetes receiving hemodialysis. We collected demographics, baseline characteristics, and glucometric data focusing on episodes of hypoglycemia with glucose cutoffs <70, <54, and <40 mg/dl. Detailed glucose and insulin data for 24 hours before and after hemodialysis was analyzed for each patient in context of a hypoglycemic episode. T-tests, one-way ANOVA, and chi-square tests were used for statistical analysis. RESULTS: At least one glucose value less than 70 mg/dl was observed in 51% of hemodialysis patients, less than 54 mg/dl in 28%, and less than 40 mg/dl in 11%. Patients with hypoglycemia had a higher HbA1c, standard deviation of glucose ( P = .0009) and higher total daily dose (TDD) of insulin by weight (0.34 units/kg vs 0.23 units/kg, P = .003). We observed a linear increasing risk for hypoglycemia with increasing TDD, with nearly 65% of hypoglycemic episodes occurring with TDD >0.20 units/kg. A majority (61%) of all hypoglycemic episodes occurred in the 24 hours prior to a hemodialysis session. Type 1 diabetes was independently associated with hypoglycemia. CONCLUSIONS: Hospitalized diabetes patients undergoing hemodialysis were found to have high rates of hypoglycemia. Our results support using a lower TDD of insulin in this population (<0.23 units/kg/day) and recommend special caution in those with type 1 diabetes.

PATHOPHYSIOLOGY AND MANAGEMENT OF HYPOGLYCEMIAIN END-STAGE RENAL DISEASE PATIENTS: A REVIEW.

OBJECTIVE: This review focuses on hypoglycemia in patients with end-stage renal disease (ESRD). It discusses the pathophysiology of glucose metabolism in the kidney, the impact of dialysis on glucose and insulin metabolism, and the challenges of glucose monitoring in ESRD. The clinical relevance of these changes is reviewed in relation to altered blood glucose targets and modification of antidiabetes therapy to prevent hypoglycemia. Based on current data and guidelines, recommendations for the outpatient and inpatient setting are provided for diabetes management in ESRD. METHODS: PubMed, OVID, and Google Scholar were searched to identify related articles through May 2016 using the following keywords: "glucose metabolism," "kidney," "diabetes," "hypoglycemia," "ESRD," and "insulin" in various combinations for this review. RESULTS: In ESRD, a combination of impaired insulin clearance, changes in glucose metabolism, and the dialysis process make patients vulnerable to low blood glucose levels. Hypoglycemia accounts for up to 3.6% of all ESRD-related admissions. At admission or during hospitalization, hypoglycemia in ESRD has a poor prognosis, with mortality rates reported at 30%. Several guidelines suggest a modified hemoglobin A1c (A1c) goal of 7 to 8.5% (53 to 69 mmol/mol) and an average blood glucose goal of 150 to 200 mg/dL. Noninsulin antidiabetes agents like dipeptidyl peptidase 4 inhibitors, repaglinide, and glipizide in appropriate doses and reduction of insulin doses up to 50% may help decrease hypoglycemia. CONCLUSION: Patients with ESRD are at high risk for hypoglycemia. Increased awareness by providers regarding these risks and appropriate diabetes regimen adjustments can help minimize hypoglycemic events. ABBREVIATIONS: ADA = antidiabetes agent BG = blood glucose CKD = chronic kidney disease DPP-4 = dipeptidyl peptidase 4 eGFR = estimated glomerular filtration rate ESRD = end-stage renal disease GFR = glomerular filtration rate HD = hemodialysis NPH = neutral protamine Hagedorn PD = peritoneal dialysis SA = short acting SU = sulfonylurea.

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.

Can a single interactive seminar durably improve knowledge and confidence of hospital diabetes management?

BACKGROUND: Safe and effective diabetes management in the hospital is challenging. Inadequate knowledge has been identified by trainees as a key barrier. In this study we assess both the short-term and long-term impact of an interactive seminar on medical student knowledge and comfort with hospital diabetes management. METHODS: An interactive seminar covering hospital diabetes management and utilizing an audience response system was added to the third-year medical student curriculum. Students were given a multiple choice assessment immediately before and after the seminar to assess their comprehension of the material. Students were also asked to rate their confidence on this topic. Approximately 6 months later, students were given the same assessment to determine if the improvements in hospital diabetes knowledge and confidence were durable over time. Students from the preceding medical school class, who did not have a hospital diabetes seminar as a part of their curriculum, were used as a control. RESULTS: Fifty-three students participated in the short-term assessment immediately before and after the seminar. The mean score (maximum 15) was 7.7 +/- 2.7 (51%) on the pre-test and 11.4 +/- 1.8 (76%) on the post-test (p < 0.01). 75 students who attended the seminar completed the same set of questions 6 months later with mean score of 9.2 ± 2.3 (61%). The control group of 100 students who did not attend seminar had a mean score of 8.8 ± 2.5 (58%). The difference in scores between the students 6-months after the seminar and the control group was not significantly different (p = 0.30). CONCLUSIONS: Despite initial short-term gains, a single seminar on hospital diabetes management did not durably improve trainee knowledge or confidence. Addition of repeated and focused interactions during clinical rotations or other sustained methods of exposure need to be evaluated.

Prevalence and Determinants of Glycemic Abnormalities in Cardiac Surgery Patients without a History of Diabetes: A Prospective Study.

OBJECTIVE: To evaluate the prevalence and persistence of postoperative glycemic abnormalities in patients without a history of diabetes, undergoing cardiac surgery (CS). METHODS: Ninety-two patients without diabetes with planned elective CS procedures at a tertiary institution were evaluated preoperatively and 3 months postoperatively for measures of glucose control including hemoglobin A1c, fasting plasma glucose, 2-h post oral glucose load, and insulin levels. Data from the hospital course were recorded. RESULTS: Valid data were available from 61 participants at 3 months; 59% had prediabetes and 10% had diabetes preoperatively by one or more diagnostic criteria and continued to be dysglycemic at 3 months. Preoperative A1C was an independent predictor of postoperative hyperglycemia (p = 0.02). Insulin resistance and BMI rather than glycemic abnormalities before surgery were associated with a longer duration of the postoperative insulin infusion (p = 0.004, p = 0.048). CONCLUSION: Seventy percent of CS patients without known diabetes met criteria for diabetes or prediabetes preoperatively, and these abnormalities persisted after surgery.

The potential role of incretin therapy in the hospital setting.

Hyperglycemia has been associated with increased morbidity and mortality in hospitalized patients. Insulin has traditionally been the drug of choice for managing hyperglycemia in this setting, but carries a significant risk of hypoglycemia. Incretin-based therapies, including glucagon-like peptide-1, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, have potential use in the hospital. These agents have a relatively low risk of hypoglycemia, favorable short-term side effect profile, and can be used alone or in combination with insulin. Several small studies have supported the safety and efficacy of incretin therapies in the inpatient setting with the majority of data coming from the intensive care setting. Large-scale clinical studies are needed to further evaluate the potential role of incretins in the management of inpatient hyperglycemia.

Compact, power-efficient architectures using microvalves and microsensors, for intrathecal, insulin, and other drug delivery systems.

This paper describes a valve-regulated architecture, for intrathecal, insulin and other drug delivery systems, that offers high performance and volume efficiency through the use of micromachined components. Multi-drug protocols can be accommodated by using a valve manifold to modulate and mix drug flows from individual reservoirs. A piezoelectrically-actuated silicon microvalve with embedded pressure sensors is used to regulate dosing by throttling flow from a mechanically-pressurized reservoir. A preliminary prototype system is demonstrated with two reservoirs, pressure sensors, and a control circuit board within a 130cm(3) metal casing. Different control modes of the programmable system have been evaluated to mimic clinical applications. Bolus and continuous flow deliveries have been demonstrated. A wide range of delivery rates can be achieved by adjusting the parameters of the manifold valves or reservoir springs. The capability to compensate for changes in delivery pressure has been experimentally verified. The pressure profiles can also be used to detect catheter occlusions and disconnects. The benefits of this architecture compared with alternative options are reviewed.

Diabetes and stress hyperglycemia in the intensive care unit: outcomes after cardiac surgery.

BACKGROUND: Hyperglycemia is common in the post-cardiac surgery population and has been associated with increased mortality rates, surgical length of stay, and infection rates. Although hospitalized patients with diabetes are known to have more complications, recent studies in various hospital settings have reported worse outcomes in patients with stress hyperglycemia than in those with diabetes. AIM: The primary objective of this study was to analyze 30- and 90-day mortality rates in post-cardiac surgery patients with stress hyperglycemia and diabetes who were managed to achieve similar moderate blood glucose goals using the University of Michigan Hospital (Ann Arbor, MI) insulin protocol between 2005 and 2008. The secondary outcomes were rates of postoperative complications, including hypoglycemia. METHODS: A standardized glucose management program was followed to treat all patients in the cardiac intensive care unit, with a blood glucose goal of 100 to 140 mg/dL. Data from 1973 patients with either diabetes or stress hyperglycemia were analyzed to identify associations between mean postoperative blood glucose levels and mortality, incidence of hypoglycemia, and complication rates. RESULTS: Mortality rates did not differ between patients with diabetes and stress hyperglycemia (3.4 and 2.3%; P = 0.2). Rates of severe hypoglycemia were low (1%) for both groups and were not associated with an increase in mortality (P = 0.95). Other complication rates were similar between patients with diabetes and stress hyperglycemia. CONCLUSION: Maintaining a blood glucose range between 100 to 140 mg/dL in post-cardiac surgery patients was associated with a low mortality rate, low risk of hypoglycemia, and with complications rates that were similar in patients with diabetes and stress hyperglycemia.

Evaluation of hemoglobin A1c criteria to assess preoperative diabetes risk in cardiac surgery patients.

OBJECTIVE: Hemoglobin A1c (A1C) has recently been recommended for diagnosing diabetes mellitus and diabetes risk (prediabetes). Its performance compared with fasting plasma glucose (FPG) and 2-h post-glucose load (2HPG) is not well delineated. We compared the performance of A1C with that of FPG and 2HPG in preoperative cardiac surgery patients. METHODS: Data from 92 patients without a history of diabetes were analyzed. Patients were classified with diabetes or prediabetes using established cutoffs for FPG, 2HPG, and A1C. Sensitivity and specificity of the new A1C criteria were evaluated. RESULTS: All patients diagnosed with diabetes by A1C also had impaired fasting glucose, impaired glucose tolerance, or diabetes by other criteria. Using FPG as the reference, sensitivity and specificity of A1C for diagnosing diabetes were 50% and 96%, and using 2HPG as the reference they were 25% and 95%. Sensitivity and specificity for identifying prediabetes with FPG as the reference were 51% and 51%, respectively, and with 2HPG were 53% and 51%, respectively. One-third each of patients with prediabetes was identified using FPG, A1C, or both. When testing A1C and FPG concurrently, the sensitivity of diagnosing dysglycemia increased to 93% stipulating one or both tests are abnormal; specificity increased to 100% if both tests were required to be abnormal. CONCLUSIONS: In patients before cardiac surgery, A1C criteria identified the largest number of patients with diabetes and prediabetes. For diagnosing prediabetes, A1C and FPG were discordant and characterized different groups of patients, therefore altering the distribution of diabetes risk. Simultaneous measurement of FGP and A1C may be a more sensitive and specific tool for identifying high-risk individuals with diabetes and prediabetes.

Micromachined bulk PZT tissue contrast sensor for fine needle aspiration biopsy.

This paper describes a micromachined piezoelectric sensor, integrated into a cavity at the tip of a biopsy needle, and preliminary experiments to determine if such a device can be used for real-time tissue differentiation, which is needed for needle positioning guidance during fine needle aspiration (FNA) biopsy. The sensor is fabricated from bulk lead zirconate titanate (PZT), using a customized process in which micro electro-discharge machining is used to form a steel tool that is subsequently used for batch-mode ultrasonic micromachining of bulk PZT ceramic. The resulting sensor is 50 microm thick and 200 microm in diameter. It is placed in the biopsy needle cavity, against a steel diaphragm which is 300 microm diameter and has an average thickness of 23 microm. Devices were tested in materials that mimic the ultrasound characteristics of human tissue, used in the training of physicians, and with porcine fat and muscle tissue. In both schemes, the magnitude and frequency of an electrical impedance resonance peak showed tissue-specific characteristics as the needle was inserted. For example, in the porcine tissue, the impedance peak frequency changed approximately 13 MHz from the initial 163 MHz, and the magnitude changed approximately 1600 Omega from the initial 2100 Omega, as the needle moved from fat to muscle. Samples including oils and saline solution were tested for calibration, and an empirical tissue contrast model shows an approximately proportional relationship between measured frequency shift and sample acoustic impedance. These results suggest that the device can complement existing methods for guidance during biopsies.