Glycemic control is associated with lower odds of mortality and successful extubation in severe COVID-19

Context Corticosteroids, specifically dexamethasone, have become the mainstay of treatment for moderate to severe COVID-19. Although the RECOVERY trial did not report adverse effects of corticosteroids, the METCOVID (Methylprednisolone as Adjunctive Therapy for Patients Hospitalized with COVID-19) study reported a higher blood glucose level in patients receiving methylprednisolone. Objectives This study aims to analyze the association between corticosteroids and COVID-19–related outcomes in patients admitted to the medical ICU (MICU) for COVID-19 pneumonia. Methods This is an observational study of 141 patients admitted to the MICU between March 18 and June 7, 2020. Data on demographics, laboratory and imaging studies, and clinical course were obtained, including data on corticosteroid use. Bivariate analyses and logistic regression were performed between patient characteristics and mortality and successful extubation. Results Of the 141 patients, 86 required mechanical ventilation, 50 received steroids, and 71 died. Regarding demographics, patients had a median age of 58 (interquartile range [IQR] 48, 65), Hispanic (57.4%, n=81), and non-Hispanic Black (37.5%, n=53). The most prevalent comorbidities were hypertension (49.6%, n=70) and diabetes (48.2%, n=68). Lower blood glucose levels on admission (125.5 vs. 148 mg/dL, p=0.025) and lower peak blood glucose levels on corticosteroids (215.5 vs. 361 mg/dL, p=0.0021) were associated with lower prevalence of mortality. Patients who were successfully extubated had a lower admission blood glucose (126.5 vs. 149 mg/dL, p=0.0074) and lower peak blood glucose on corticosteroids (217 vs. 361 mg/dL, p=0.0023). Conclusions Lower blood glucose on admission and lower maximum blood glucose on corticosteroids were associated with lower odds of mortality and successful extubation, regardless of preexisting diabetes. Hyperglycemia may be negating any potential benefit of corticosteroid therapy. These findings suggest that glucose control could be a parameter that impacts the outcome of patients receiving corticosteroids for COVID-19 pneumonia.

Acute Metabolic Responses to Glucose and Fructose Supplementation in Healthy Individuals: A Double-Blind Randomized Crossover Placebo-Controlled Trial

The aim of this study was to investigate the impact of glucose (Glu), fructose (Fru), glucose and fructose (GluFru) and sucralose on blood glucose response in healthy individuals. Fifteen healthy individuals (five females, age of 25.4 ± 2.5 years, BMI of 23.7 ± 1.7 kg/m2 with a body mass (BM) of 76.3 ± 12.3 kg) participated in this double-blind randomized crossover placebo-controlled trial. Participants received a mixture of 300 mL of water with 1 g/kg BM of Glu, 1 g/kg BM of Fru, 0.5 g/kg BM of GluFru (each), and 0.2 g sucralose as a placebo. Peak BG values Glu were reached after 40 ± 13 min (peak BG: 141 ± 20 mg/dL), for Fru after 36 ± 22 min (peak BG: 98 ± 7 mg/dL), for GluFru after 29 ± 8 min (BG 128 ± 18 mg/dL), and sucralose after 34 ± 27 min (peak BG: 83 ± 5 mg/dL). Significant differences regarding the time until peak BG were found only between Glu and GluFru supplementation (p = 0.02). Peak blood glucose levels were significantly lower following the ingestion of Fru compared to the supplementation of Glu and GluFru (p < 0.0001) while Glu and GluFru supplementation showed no difference in peak values (p = 0.23). All conditions led to a significantly higher peak BG value compared to sucralose (p < 0.0001). Blood lactate increased in Glu (p = 0.002), Fru and GluFru (both p < 0.0001), whereas sucralose did not increase compared to the baseline (p = 0.051). Insulin levels were significantly higher in all conditions at peak compared to sucralose (p < 0.0001). The findings of this study prove the feasibility of combined carbohydrate supplementations for many applications in diabetic or healthy exercise cohorts.

Safety assessment and potential risks of the glucagon stimulation test in the diagnosis of secondary adrenal insufficiency

Background: Although it takes more time, the glucagon stimulation test (GST) is a reliable measure for assessing growth hormone (GH) and adrenocorticotropic hormone (ACTH) secretion. The GST is considered to be a safe test, however, it still has mild side effects and potential risks. Objective : The objective of this study was to analyze the side effects of the GST while testing adrenal insufficient patients. Methods: This was a prospective study in which GST was performed in eighty-one patients (44 men, 37 women, mean age: 35.83±19.62 years) with pituitary disorder. The GST consisted in an intramuscular injection of 1 mg of glucagon. Blood samples were collected at baseline, and 30, 60, 90, 120, 150, 180 and 210 min after glucagon injection for cortisol measurements. All patients were asked to report side-effects associated with this test. Results: The mean peak blood glucose level under GST was 9.01±2.03 mmol/L and the mean glycemic nadir was 4.34±1.75 mmol/L was found most frequently during the 30th minute (p <10-3). During the test, 35 subjects (43.2%) had side effects with a mean age of 42.89 ± 19.75 years. Frequent side effects included: nausea (29.62%), vomiting (27.16%), abdominal cramps (18.51%) and hunger (13.58%). All patients tolerated the test until the end. Adverse effects were significantly more prevalent in patients older than 50 years (p=0.012). Conclusions: The GST is a reliable alternative to assess hypothalamic pituitary adrenal axis but should be cautiously used especially in the elderly although its minor side effects.

Association of Hyperglycaemia with Outcome in Critically Ill Children in Central India - A Prospective Study

BACKGROUND Hyperglycaemia is a common occurrence in children with critical illness. Several studies relate hyperglycaemia occurring during intensive care unit (ICU) admission to be associated with increased mortality. We wanted to evaluate the incidence of hyperglycaemia and its association with mortality among critically ill children. METHODS A prospective observational study was conducted among critically ill children admitted to the Paediatric Intensive Care Unit (PICU) of a tertiary care centre, Raipur, Chhattisgarh in central India, from 1st May 2016 to 31st October 2016. All patients aged 1 month to 14 years who were admitted in PICU during this study period (N = 113) were included. Children who were known cases of diabetes mellitus, hepatic failure or renal failure requiring dialysis and children who left against medical advice (LAMA) or died within 24 hours of admission were excluded (N = 13). Thus 100 children were included in the study. RESULTS In the study population, incidence of hyperglycaemia was 60 %; overall 37 (37 %) died and the mortality rate was significantly higher (46.6 % vs. 19.4 %) in children with hyperglycaemia than in children without hyperglycaemia. Nonsurvivors had higher mean blood glucose levels at 48 hours (218.35 ± 87.42 mg / dL) than survivors (141.12 ± 55.26 mg / dL) (P < .001). Peak blood glucose (218.35 ± 87.42 mg / dL vs. 141.12 ± 55.26 mg / dL), need for mechanical ventilation (54.5 % vs. 27.3 %), need for inotropes (76.4 % vs. 23.5 %) and Paediatric Risk of Mortality Score (PRISM) III (16.25 ± 5.46 vs. 9.06 ± 4.35) were significantly higher in non-survivors than in survivors. On regression analysis, blood sugar at 24 hours and duration of stay were found to be significant. CONCLUSIONS In this study, in the PICU, the mortality rate was significantly higher in children with hyperglycaemia than in children without hyperglycaemia. Non-survivors had significantly higher mean blood glucose levels at 48 hours than survivors. Peak blood glucose, need for mechanical ventilation, need for inotropes and PRISM III scores were significantly higher in non-survivors than in survivors. KEYWORDS Hyperglycaemia, Critically Ill, PICU, Outcome, Mortality

Glycemic Response to Two Doses of Resistant Starch Type 4: A Randomized Controlled Crossover Trial (P08-091-19)

Objectives Resistant starches (RS) have a beneficial effect on glucose and insulin responses in the postprandial period following carbohydrate (CHO) consumption. In comparison to resistant starch types 1–3, there is little evidence investigating the effects of resistant starch type 4 (RS4) on these metabolic responses. The primary aim of the current study was to determine whether the glycemic response to a nutritional RS4 bar (RS4) was different compared to a puffed wheat bar (PWB), provided at the standard testing amount of 50 g available CHO and a lower dose of 30 g available CHO, thereby investigating a dose-response effect. Methods Apparently healthy adults (n = 15; 26.1 ± 4.8yrs) participated in this controlled randomized crossover trial. All participants completed six trials: 50 g dextrose control drink (50DEX), 30 g dextrose control drink (30DEX); and nutrition bars containing: 50 g available CHO of PWB or RS4 (50PWB; 50RS4), and 30 g available CHO PWB or RS4 (30PWB; 30RS4). Participants fasted for 10–12 hrs prior to each visit with a minimum 72hr washout period between trials. Blood glucose was measured via LDX Cholestech at baseline and 10, 20, 30, 60, 90, and 120 min post consumption. Primary outcomes were determined using mixed-effects models in GraphPad Prism 8.0.1. Results Glucose incremental area under the curve (iAUC) was not significantly different between the 50 g conditions (P = 0.054). However, peak blood glucose was significantly lower in the 50RS4 condition compared to 50PWB and 50CON (P = 0.027; P = 0.004 respectively); and there was no difference between 50PWB and 50CON (P = 0.496). While 30RS4 and 30PWB glucose iAUCs were lower compared to 30CON (P = 0.002), there was no difference between 30RS4 and 30PWB (P = 0.48). Peak blood glucose was reduced for both 30PWB and 30RS4 when compared to 30CON (P = 0.005; P = 0.002 respectively), with no difference between 30 g CHO bars (P = 0.22). Conclusions These results indicate a potential dose-response effect for RS4 on postprandial glycemia. Specifically, at the 50 g available CHO standard testing amount, RS4 reduced peak blood glucose as compared to the 50PWB control. At the lower dose of available CHO, there was not a statistically significant beneficial effect for 30RS4 on postprandial glycemia. There may be a potential floor effect where RS4 has no further benefit when available CHO is low. Funding Sources MGP Ingredients Inc.

Swertiamarin Contributes to Glucose Homeostasis via Inhibition of Carbohydrate Metabolizing Enzymes

<strong>Objective:</strong> Swertiamarin is a common secoiridoid found among the members of Gentianaceae. The present study aimed to establish the effectiveness of swertiamarin in achieving glucose homeostasis via inhibition of carbohydrate metabolizing enzymes by in-vitro and in-vivo studies. <strong>Materials and methods:</strong> Swertiamarin was obtained from dried whole plant samples of <em>Enicostemma littorale</em> Blume chromatographic fractionation over the silica gel column. Its effect on carbohydrate metabolizing enzymes viz., α-amylase and α-glucosidase were evaluated at 0.15 to 10 mg/mL in-vitro. The results were supplemented by anti-hyperglycemic studies in carbohydrate challenged mice pretreated with swertiamarin at a dose of 20 mg/kg body weight orally. <strong>Results:</strong> Swertiamarin was effective in inhibiting α-amylase and α-glucosidase with IC<em>50</em> values of 1.29±0.25 mg/mL and 0.84±0.11 mg/mL, respectively. The studies in starch and sucrose challenged mice showed that swertiamarin effectively restricted the increase in the peak blood glucose level (BGL). The increase in peak BGL was 49 mg/dL and 57 mg/dL only in the treatment groups compared to 70 mg/dL and 80 mg/dL in untreated groups after 30 min in starch and sucrose-fed mice, respectively. Acarbose (10 mg/kg b.w.) also produced significant (p&lt;0.01) blood glucose lowering response in both the models. <strong>Conclusion:</strong> Swertiamarin was effective in the achieving stricter glycemic control in carbohydrate challenged mice through the inhibition of carbohydrate metabolizing enzymes.

Association of increased morbidity with the occurrence of hyperglycemia in the immediate postoperative period after elective pediatric neurosurgery

OBJECTIVE The acute elevation of blood glucose in perioperative pediatric patients subjected to cardiac surgery and in victims of head trauma is associated with higher rates of postoperative complications. Data on the occurrence of hyperglycemia and its association with unfavorable outcomes among patients who have undergone elective neurosurgery are scarce in the literature. This study aimed to determine whether the occurrence of hyperglycemia during the perioperative period of elective neurosurgery for the resection of tumors of the CNS in children is associated with increased morbidity. METHODS This retrospective cohort analysis included 105 children up to 12 years of age who underwent elective neurosurgery for resection of supratentorial and infratentorial CNS tumors between January 2005 and December 2010 at the São Rafael Hospital, a tertiary care medical center in Salvador, Brazil. Demographic data and intraoperative and postoperative information were collected from the medical records. Differences in blood glucose levels during the perioperative period were evaluated with nonparametric tests. RESULTS The patients who developed postoperative complications exhibited higher blood glucose levels on admission to the intensive care unit (ICU) (162.0 ± 35.8 mg/dl vs 146.3 ± 43.3 mg/dl; p = 0.016) and peak blood glucose levels on postoperative Day 1 (171.9 ± 30.2 mg/dl vs 156.1 ± 43.2 mg/dl; p = 0.008). Multivariate analysis showed that peak blood glucose levels on postoperative Day 1 were independently associated with a higher odds ratio for postoperative complication (OR 1.05). The occurrence of hyperglycemia (>150 mg/dl) upon admission to the ICU was associated with longer ICU (p = 0.003) and hospital (p = 0.001) stays. CONCLUSIONS The occurrence of hyperglycemia during the postoperative period after elective pediatric neurosurgery for the resection of CNS tumors was associated with longer hospital and ICU stays. Postoperative complications were associated with higher blood glucose levels upon admission to the ICU and higher peak blood glucose on the first postoperative day.

Increasing the viscosity of oat β-glucan beverages by reducing solution volume does not reduce glycaemic responses

The soluble fibre (1 → 3)(1 → 4)-β-d-glucan attenuates postprandial glycaemic responses when administered in solution. This attenuating effect is strengthened when solution viscosity is increased by increasing the β-glucan dose or molecular weight (MW). The effect of varying solution viscosity by changing solution volume, without changing the β-glucan dose or MW, on glycaemic responses was determined. A total of fifteen healthy subjects received six 50 g oral glucose beverages prepared with or without 4 g of high-MW (HMW, 580 000 g/mol) or low-MW (LMW, 145 000 g/mol) β-glucan, with a beverage volume of 250 or 600 ml. Postprandial plasma glucose concentration was measured over 2 h, and the peak blood glucose rise (PBGR) and the incremental area under the glycaemic response curve (AUC) were calculated. Subjects served as their own controls. The physico-chemical properties of the beverages were measured to examine their relationship with glycaemic response results. The HMW β-glucan beverage was more viscous and achieved greater reductions in PBGR than the glucose beverage with LMW β-glucan (P< 0·05). At the same MW, the 250 and 600 ml β-glucan beverages differed in viscosity (>9-fold difference) but not in PBGR (P>0·05). No differences in AUC were detected among the beverages (P= 0·147). The effects of β-glucan on glycaemic response were altered by changes in beverage viscosity achieved through changes in MW but not in volume. Therefore, β-glucan dose and MW are the most vital characteristics for optimising the bioactivity of β-glucan solutions with respect to glycaemic response.