Management of Hyperglycemia in the Noncritical Care Setting: A Real-World Case-Based Approach With Alternative Insulin- and Noninsulin-Based Strategies.

Insulin remains the mainstay of treatment for inpatient hyperglycemia in the United States and Canada. However, some other countries commonly use noninsulin agents such as metformin and sulfonylureas, and several trials have demonstrated the efficacy and safety of incretin-based agents in patients with type 2 diabetes who are admitted to noncritical care medicine and surgery services. There is a high degree of interest in alternative glucose-lowering strategies to achieve favorable glycemic outcomes with lower risks of hypoglycemia. In this case series, we highlight the challenges of inpatient glycemic management and the need for alternatives to the traditional basal-bolus insulin regimen. Additional investigation will be imperative to validate the safety and efficacy of appropriate insulin and noninsulin treatments and to further develop guidelines that are applicable in real-world hospital settings.

Outcomes of "Real-World" Insulin Strategies in the Management of Hospital Hyperglycemia.

CONTEXT: Guidelines recommend scheduled long-acting basal and short-acting bolus insulin several times daily to manage inpatient hyperglycemia. In the "real world," insulin therapy is complicated, with limited data on the comparative effectiveness of different insulin strategies. OBJECTIVE: This work aimed to evaluate the association of different insulin strategies with glucose control and hospital outcomes after adjustment for patient and physician factors that influence choice of therapy. METHODS: This retrospective, observational study took place at an academic hospital. Participants included noncritically ill hospitalized medical/surgical patients (n = 4558) receiving subcutaneous insulin for 75% or longer during admission. Insulin therapy was grouped into 3 strategies within the first 48 hours: basal bolus (BB: scheduled long and short/rapid n = 2358), sliding scale (SS: short/rapid acting n = 1855), or basal only (BO: long only: n = 345). Main outcome measures included glucose control: hypoglycemic days, hyperglycemic days, euglycemic days, mean glucose; and hospitalization: in-hospital mortality, length of stay (LOS), and readmissions. RESULTS: Initial therapy with BB was associated with more hypoglycemic (2.40; CI, 2.04 to 2.82) (P < .001) and fewer euglycemic days (0.90; CI, 0.85 to 0.97) (P = .003) than SS, whereas BO was associated with fewer hyperglycemic days (0.70; CI, 0.62 to 0.79) (P < .001), lower mean glucose (-18.03; CI, -22.46 to -12.61) (P < .001), and more euglycemic days (1.22; CI, 1.09 to 1.37) (P < .001) compared to SS. No difference in mortality, LOS, and readmissions was found. However, decreased LOS was observed in the BB subgroup with a medical diagnostic related group (0.93; CI, 0.89 to 0.97) (P < .001). CONCLUSION: BO had a more favorable hyperglycemia profile than SS. BB, on the other hand, showed worse glycemic control as compared to SS. In the real-world hospital, BO may be a simpler and more effective insulin strategy.

Continuous Glucose Monitoring in Critically Ill Patients With COVID-19: Results of an Emergent Pilot Study.

BACKGROUND: Amidst the coronavirus disease 2019 (COVID-19) pandemic, continuous glucose monitoring (CGM) has emerged as an alternative for inpatient point-of-care blood glucose (POC-BG) monitoring. We performed a feasibility pilot study using CGM in critically ill patients with COVID-19 in the intensive care unit (ICU). METHODS: Single-center, retrospective study of glucose monitoring in critically ill patients with COVID-19 on insulin therapy using Medtronic Guardian Connect and Dexcom G6 CGM systems. Primary outcomes were feasibility and accuracy for trending POC-BG. Secondary outcomes included reliability and nurse acceptance. Sensor glucose (SG) was used for trends between POC-BG with nursing guidance to reduce POC-BG frequency from one to two hours to four hours when the SG was in the target range. Mean absolute relative difference (MARD), Clarke error grids analysis (EGA), and Bland-Altman (B&A) plots were calculated for accuracy of paired SG and POC-BG measurements. RESULTS: CGM devices were placed on 11 patients: Medtronic (n = 6) and Dexcom G6 (n = 5). Both systems were feasible and reliable with good nurse acceptance. To determine accuracy, 437 paired SG and POC-BG readings were analyzed. For Medtronic, the MARD was 13.1% with 100% of readings in zones A and B on Clarke EGA. For Dexcom, MARD was 11.1% with 98% of readings in zones A and B. B&A plots had a mean bias of -17.76 mg/dL (Medtronic) and -1.94 mg/dL (Dexcom), with wide 95% limits of agreement. CONCLUSIONS: During the COVID-19 pandemic, CGM is feasible in critically ill patients and has acceptable accuracy to identify trends and guide intermittent blood glucose monitoring with insulin therapy.

Comparison of Levothyroxine Dosing in Patients with and without Heart Failure.

Background: Evidence has shown that low thyroid hormone levels may lead to worse prognosis including a higher mortality rate in patients with heart failure (HF). Thyroid replacement increases cardiac output and exercise performance without causing significant adverse events. The purpose of this study is to compare levothyroxine doses in patients with and without HF.Methods: This single center, retrospective cohort study compared levothyroxine doses in ambulatory hypothyroid patients with a history of HF to those without a history of HF. Patients were stratified into three groups: no HF, HF with reduced ejection fraction (HFrEF, EF<40%), and other types of HF. The primary endpoint of average levothyroxine dose was analyzed using multivariable linear regression with variables determined a priori.Results: Three hundred patients were included in the study with 100 patients in each arm. Average levothyroxine doses (mcg/kg) were 1.5 ± 0.7, 1.6 ± 0.8, and 1.6 ± 0.9 for no HF, other types of HF, HFrEF, respectively (p= .61). Factors found to be significantly related to levothyroxine dosing included gender, drug-drug interactions, and the timing of clinic visit to lab draw. No differences were found in secondary outcomes including TSH levels, free T4, T3, and percentage of patients with elevated thyroid-stimulating hormone (TSH) among HFrEF, other types of HF, and no HF patients. Among HF patients, average ejection fractions were also similar comparing patients with elevated TSH, normal TSH, and low TSH.Conclusion: The dose of levothyroxine was not significantly different in HF patients compared to patients without HF.

Prediabetes: Why Should We Care?

A clear link between cardiovascular disease and prediabetes has emerged over the past few years. Recent studies have shown that patients with prediabetes can suffer from coronary artery disease and diastolic heart failure even before progressing to overt diabetes. With this knowledge, physicians must identify prediabetes and take appropriate measures to optimize glycemic control. The pathophysiological defect seen in prediabetes can be managed with lifestyle modifications; thus, it is essential that physicians have a clear understanding of the current recommendations regarding diet and exercise. This review outlines the complications associated with prediabetes, presents an overview of the available pharmacological and surgical therapies that are effective in treating it, and provides a stepwise, multipronged approach for management.

Hypothyroidism and the Heart.

Hypothyroidism is a commonly encountered clinical condition with variable prevalence. It has profound effects on cardiac function that can impact cardiac contractility, vascular resistance, blood pressure, and heart rhythm. With this review, we aim to describe the effects of hypothyroidism and subclinical hypothyroidism on the heart. Additionally, we attempt to briefly describe how hypothyroid treatment affects cardiovascular parameters.

Short palate, lung, and nasal epithelial clone-1 is a tightly regulated airway sensor in innate and adaptive immunity.

Short palate, lung, and nasal epithelial clone-1 (SPLUNC1) is a protein abundantly expressed by the respiratory epithelium of the proximal lower respiratory tract, a site of great environmental exposure. Previous studies showed that SPLUNC1 exerts antimicrobial effects, regulates airway surface liquid and mucociliary clearance, and suppresses allergic airway inflammation. We studied SPLUNC1 to gain insights into its role in host defense. In the lower respiratory tract, concentrations of SPLUNC1 are high under basal conditions. In models of pneumonia caused by common respiratory pathogens, and in Th1-induced and Th2-induced airway inflammation, SPLUNC1 secretion is markedly reduced. Pathogen-associated molecular patterns and IFN-γ act directly on airway epithelial cells to inhibit SPLUNC1 mRNA expression. Thus, SPLUNC1 is quickly suppressed during infection, in response to an insult on the epithelial surface. These experiments highlight the finely tuned fluctuations of SPLUNC1 in response to exposures in the respiratory tract, and suggest that the loss of SPLUNC1 is a crucial feature of host defense across air-breathing animal species.

Contemporary review of drugs used to treat obesity.

Obesity, classified by the American Medical Association in 2013 as a disease, is an epidemic that is drawing serious global attention. It is the most common preventable disease and the most common modifiable risk factor for several chronic diseases. It is an independent cause of increased morbidity and mortality. Obesity is spreading across most countries, socio-economic strata, age groups, gender groups, and races, albeit to variable degrees. It is concerning that both adults and children are increasingly afflicted by obesity. Both incidence and prevalence of the disease are on the rise. The direct and indirect costs attributable to obesity have reached billions of US dollars. Obesity management involves a multi-disciplinary approach that includes the patient and his or her family, the primary care provider, a dietician or nutrition specialist and physical trainer. It may also require specialist care in the use of pharmacological and surgical interventions. Currently available anti-obesity drugs are indicated for those who are obese (BMI of 30 kg/m(2)) or overweight (BMI of 27 kg/m(2)) with at least one weight-related comorbid condition. This article focuses on the FDA-approved antiobesity drugs, their mechanisms of action, chemical structures, efficacy, safety profiles and known side effects.

Reshaping pre-clerkship years in reproductive medicine education.

The educational program of the Paul L. Foster School of Medicine in El Paso, Texas integrates the basic and clinical sciences and organizes them according to the organ-system based units. The reproduction unit focuses on human reproduction, pregnancy and illnesses associated with the female genital tract and breast. The sequence of 13 clinical presentations is structured so that the concepts developed during the study of one topic lays down a foundation for subsequent topics. Students are provided with a brief definition and a statement of clinical significance for each clinical presentation, which serves as the foundation for presentations of both clinical and basic science information. In the Medical Skills Course, students practice skills and behaviors associated with obstetrics and gynecology (Ob Gyn) history taking, culturally sensitive communication skills, conducting and recording of physical and pelvic examinations as they relate to clinical presentations. The Society, Community and Individual Course focuses on real life experience in a local community clinic setting and improves the understanding of the social determinants of female reproductive health. We believe that our pedagogical approach enhances knowledge comprehension, improves knowledge retention of the basic science and promotes the development of clinical reasoning, enabling easier transition to the clerkship years.

Discovery of functional motifs in h-regions of trypanosome signal sequences.

N-terminal signal peptides direct secretory proteins into the ER (endoplasmic reticulum) of eukaryotes or the periplasmic space of prokaryotes. A hydrophobic core (h-region) is important for signal sequence function; however, the mechanism of h-region action is not resolved. To gain new insight into signal sequences, bioinformatic analysis of h-regions from humans, Saccharomyces cerevisiae, Trypanosoma brucei and Escherichia coli was performed. Each species contains a unique set of peptide motifs (h-motifs) characterized by identity components (i.e. sequence of conserved amino acids) joined by spacers. Human h-motifs have four identity components, whereas those from the other species utilize three identity components. Example of h-motifs are human Hs3 {L-x(2)-[AGILPV]-L-x(0,2)-L}, S. cerevisiae Sc1 [L-x(0,2)-S-x(0,3)-A], T. brucei Tb2 {L-x(1,2)-L-[AILV]} and E. coli Ec1 [A-x(0,2)-L-x(0,3)-A]. The physiological relevance of h-motifs was tested with a T. brucei microsomal system for translocation of a VSG (variant surface glycoprotein)-117 signal peptide. Disruption of h-motifs by scrambling of sequences in h-regions produced defective signal peptides, although the hydrophobicity of the peptide was not altered. We conclude that: (i) h-regions harbour h-motifs, and are not random hydrophobic amino acids; (ii) h-regions from different species contain unique sets of h-motifs; and (iii) h-motifs contribute to the biological activity of ER signal peptides. h-Regions are 'scaffolds' in which functional h-motifs are embedded. A hypothetical model for h-motif interactions with a Sec61p protein translocon is presented.

Post-translational import of protein into the endoplasmic reticulum of a trypanosome: an in vitro system for discovery of anti-trypanosomal chemical entities.

HAT (human African trypanosomiasis), caused by the protozoan parasite Trypanosoma brucei, is an emerging disease for which new drugs are needed. Expression of plasma membrane proteins [e.g. VSG (variant surface glycoprotein)] is crucial for the establishment and maintenance of an infection by T. brucei. Transport of a majority of proteins to the plasma membrane involves their translocation into the ER (endoplasmic reticulum). Thus inhibition of protein import into the ER of T. brucei would be a logical target for discovery of lead compounds against trypanosomes. We have developed a TbRM (T. brucei microsome) system that imports VSG_117 post-translationally. Using this system, MAL3-101, equisetin and CJ-21,058 were discovered to be small molecule inhibitors of VSG_117 translocation into the ER. These agents also killed bloodstream T. brucei in vitro; the concentrations at which 50% of parasites were killed (IC50) were 1.5 microM (MAL3-101), 3.3 microM (equisetin) and 7 microM (CJ-21,058). Thus VSG_117 import into TbRMs is a rapid and novel assay to identify 'new chemical entities' (e.g. MAL3-101, equisetin and CJ-21,058) for anti-trypanosome drug development.