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The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in patients with Type 2 Diabetes Mellitus (T2DM)) trial made evident the potentiality of pharmacological ...sodium-glucose cotransporter 2 (SGLT2) inhibition for treating patients with diabetes and cardiovascular disease. Since the effect of empagliflozin or other SGLT2 inhibitors on the whole cardiac metabolic profile was never analysed before, and with the purpose to contribute to elucidate the benefits at cardiac level of the use of empagliflozin, we explored the effect of the treatment with empagliflozin for six weeks on the cardiac metabolomic profile of Zucker diabetic fatty rats, a model of early stage T2DM, using untargeted metabolomics approach. Empagliflozin reduced significantly the cardiac content of sphingolipids (ceramides and sphingomyelins) and glycerophospholipids (major bioactive contributing factors linking insulin resistance to cardiac damage) and decreased the cardiac content of the fatty acid transporter cluster of differentiation 36 (CD36); induced significant decreases of the cardiac levels of essential glycolysis intermediaries 2,3-bisphosphoglycerate and phosphoenolpyruvate, and regulated the abundance of several amino acids of relevance as tricarboxylic acid suppliers and/or in the metabolic control of the cardiac function as glutamic acid, gamma-aminobutyric acid and sarcosine. Empagliflozin treatment activated the cardioprotective master regulator of cellular energyhomeostasis AMP-activatedproteinkinase (AMPK) and enhanced autophagy at cardiac level, while it decreased significantly the cardiac mRNA levels of the pro-inflammatory cytokines interleukin-6 (IL-6), chemerin, TNF-α and MCP-1, reinforcing the hypothesis of a direct role for empagliflozin in attenuating cardiac inflammation. Our results provide an advancement on the knowledge of the mechanisms linking the therapy with empagliflozin with protective effects on the development of cardiometabolic diseases whose course is associated with remarkable cardiac bioenergetics dysregulation and disarrangement in cardiac metabolome and lipidome.
Summary
Lung damage caused by SARS‐Cov‐2 virus results in marked arterial hypoxia, accompanied in many cases by hypocapnia. The literature is inconclusive as to whether these conditions induce ...alteration of the affinity of haemoglobin for oxygen. We studied the oxyhaemoglobin dissociation curves (ODCs) of 517 patients hospitalized with coronavirus disease 2019 (COVID‐19) for whom arterial blood gas analysis (BGA) was performed upon hospitalization (i.e., before treatment). With respect to a conventional normal p50 (pO2 at 50% saturation of haemoglobin) of 27 mmHg, 76% had a lower standardized p50 (p50s) and 85% a lower in vivo p50 (p50i). In a 33‐patient subgroup with follow‐up BGAs after 3, 6, 9, 12, 15 and 18 days' treatment, p50s and p50i exhibited statistically significant differences between baseline values and values recorded at all these time points. The 30‐day Kaplan–Meier survival curves of COVID‐19 patients stratified by p50i level show a higher probability of survival among patients who at admission had p50 values below 27 mmHg (p = 0.012). Whether the observed alteration of the affinity of haemoglobin for oxygen in COVID‐19 patients is a direct or indirect effect of the virus on haemoglobin is unknown.
Background
Evidence about the association of high blood eosinophil count with asthma exacerbation is inconsistent and unclear. The objective of this meta‐analysis was to determine whether elevated ...blood eosinophil count predicts asthma exacerbation.
Methods
We searched MEDLINE, EMBASE, and additional databases, without any language restriction. We also checked the reference lists of the included studies and of relevant systematic reviews. The main outcome was the occurrence of asthma exacerbation. We calculated global pooled odds ratios (ORs) and their 95% confidence intervals (CIs) and performed predefined subgroup analyses. We appraised the quality of the studies using Newcastle‐Ottawa Scale, examined the heterogeneity between studies, assessed publication bias, and carried out sensitivity analyses.
Results
Among 1567 retrieved publications, 23 observational studies comprising 155,772 participants met the inclusion criteria. High blood eosinophil count was associated with higher odds of asthma exacerbation OR: 1.31 (95% CI: 1.16, 1.49), specifically with asthma‐related outpatient visits OR: 1.46 (95% CI: 1.25, 1.70) and emergency department visits OR: 1.63 (95% CI: 1.29, 2.07). A significant association was observed starting from an eosinophils’ cutoff value of 200 cells/μl. The association was observed for cohort studies OR: 1.30 (95%CI: 1.13, 1.49), North American studies OR: 1.43 (95%CI: 1.31, 1.57), Asian populations OR: 1.67 (95%CI: 1.34, 2.08), children OR: 1.38 (95%CI: 1.22, 1.56), and studies that adjusted for inhaled corticosteroids therapy OR: 1.42 (95%CI: 1.28, 1.56).
Conclusions
Blood eosinophil counts ≥ 200 cells/µL are associated with asthma exacerbation. Blood eosinophil count is a modifiable factor that could be addressed in asthma management strategies.
There is a growing interest in the pathopysiological consequences of postprandial hyperglycemia. It is well known that in diabetic patients 2 h plasma glucose is a better risk predictor for coronary ...heart disease than fasting plasma glucose. Data on the glycemic response in healthy people are scarce.
To evaluate the effect of macronutrients (carbohydrates, fats, and proteins) and fiber on postprandial glycemic response in an observational study of a non-diabetic adult population.
Cross-sectional study. 150 non-diabetic adults performed continuous glucose monitoring for 6 days. During this period they recorded food and beverage intake. The participants were instructed not to make changes in their usual diet and physical exercise.Variables analyzed included clinical parameters (age, sex, body weight, height, body mass index, blood pressure, and waist measurement), meal composition (calories, carbohydrates, fats, proteins, and fiber) and glycemic postprandial responses separated by sexes.The study period was defined from the start of dinner to 6 h later.
A total of 148 (51% women) subjects completed all study procedures. Dinner intake was higher in males than in females (824 vs 531 kcal). Macronutrient distribution was similar in both sexes. No significant differences were found in fiber intake between men and women (5.5 g vs 4.5 g).In both sexes, the higher intake of carbohydrates corresponded to a significantly higher glycemic response (
= 0.0001 in women,
= 0.022 in men). Moreover, in women, as fat intake was higher, a flattening of the postprandial glycemic curve was observed (
= 0.003). With respect to fiber, a significantly lower glycemic response was observed in the group of women whose fiber intake at dinner was higher (
= 0.034).
Continuous glucose monitoring provides important information about glucose levels after meals. In this study, the postprandial glycemic response in women was different from that of men, and carbohydrates were the main determinant of elevated postprandial glucose levels.
The glycation gap has been proposed as an index of nonglycemic determinants of glycated hemoglobin (Hb A(1c)). We investigated whether it predicts progression of nephropathy in type 2 diabetic ...patients.
We recorded albumin excretion rate, Hb A(1c), and serum fructosamine in 2314 patients over an average of 6.5 years. Hb A(1c) was regressed on fructosamine by using a repeated-measures longitudinal regression model and data for all visits of all patients; the raw glycation gap gg was calculated at each visit, as measured by Hb A(1c) minus the value predicted by the regression; and the mean glycation gap (GG) was defined for each patient as the mean of the values for the raw glycation gap (gg) calculated at each visit. The study group was divided into high-, medium- and low-GG groups of equal sizes, which were compared for progression of nephropathy by Cox regression analyses controlling for age, sex, duration of diabetes, initial nephropathy status, therapy, baseline Hb A(1c), mean Hb A(1c), and mean fructosamine. The design of the study was a retrospective cohort study with follow-up for 6.5 (SD 4.2) years.
The gg exhibited considerable stability over time. In the high- and medium-GG groups, the risk of progression of nephropathy was respectively 2.5 and 1.6 times that of the low-GG group (P < 0.0001 and P = 0.001, respectively) after adjustment as described above.
GG predicts the progression of nephropathy in type 2 diabetic patients independently of fructosamine and even after adjustment for Hb A(1c). The joint use of the glycation gap and fructosamine as measures of nonglycemic and glycemic determinants of glycation, respectively, may improve evaluation of the risk of nephropathy and of the glycemic control desirable for the individual patient.
The glycation gap (the difference between measured A1C and the value predicted by regression on fructosamine) is stable and is associated with microvascular complications of diabetes but has not ...hitherto been estimated within a clinically useful time frame. We investigated whether two determinations 30 days apart suffice for a reasonably reliable estimate if both A1C and fructosamine exhibit stability.
We studied 311 patients with type 1 or type 2 diabetes for whom simultaneous measurements of A1C and serum fructosamine had been made on at least two occasions separated by 1 month (t(0) and t(1)). Glycemia was deemed stable if A1C(t(1)) - A1C(t(0)) and fructosamine(t(1)) - fructosamine(t(0)) were both less than their reference change values (RCVs). Instantaneous glycation gaps gg(t(0)) and gg(t(1)) and their mean (GG), were calculated using the data from all stable patients for the required regression.
Stable glycemia was shown by 144 patients. In 90% of unstable case subjects, a change in medication was identified as the cause of instability. Among 129 stable patients with an average of eight gg determinations prior to t(0), GG correlated closely with the mean of these prior determinations (r(2) = 0.902, slope 1.025, intercept -0.038).
The glycation gap can be calculated reliably from pairs of A1C and fructosamine measurements taken 1 month apart if these measurements satisfy the RCV criteria for glycemic control.
Abstract Objectives Hypoglycemia is a limiting factor in the achievement of strict glycemic control. The primary objective of this 9-week study was to determine the frequency of hypoglycemia in ...patients with stable insulin-treated type 2 diabetes mellitus by comparing self-monitored blood glucose (SMBG) measurement with continuous glucose monitoring (CGM). Methods This was an observational prospective study. Included in the study were 63 stable, insulin-treated patients with type 2 diabetes. They were instructed to record 2 daily capillary blood glucose readings, pre- and/or postprandial, in a sequential way during 8 consecutive weeks. A CGM system was worn during an additional week. We evaluated the frequency of hypoglycemia using the 8-week SMBG profile and the 1 CGM week. Results SMBG revealed that 50% of the patients had experienced hypoglycemia. CGM found hypoglycemia in 59% of patients. Significantly higher percentages of hyperglycemic and hypoglycemic episodes were detected by CGM than by capillary blood glucose measurements (61.1% vs. 50.8%; p=0.047) and (3.8% vs. 1.7%; p=0.016); 33% of patients experienced nocturnal hypoglycemia, and 19% of patients who had no data concerning hypoglycemia recorded in the capillary blood glucose diary had experienced hypoglycemia as measured by CGM, and the hypoglycemia occurred mainly during the nocturnal period. Conclusions In stable well-controlled, insulin-treated patients with type 2 diabetes, CGM showed higher numbers of hypoglycemic events than did SMBG, especially at night. CGM is a useful tool that provides clinically valuable information about glucose control in these patients.
The concentration levels of serum free thyroxine, serum free triiodothyronine, and thyroid-stimulating hormone were measured in 20 children receiving carbamazepine, 32 children receiving valproic ...acid, and 5 children receiving phenobarbital at the following times: (1) during chronic treatment, and (2) 3 months after the end of treatment with antiepileptic drugs. Patients during chronic treatment revealed significant changes in serum thyroid hormones, especially the children treated with carbamazepine and valproic acid. A number of children receiving long-term therapy with the two last antiepileptic drugs had varying grades of subclinical hypothyroidism. Three months after the end of treatment, a complete return to normal of all parameters was observed. These data demonstrate that the changes induced by these drugs are transient and reversible.
We determined the serum concentration of biotin, zinc, antiepileptic drugs, and biotinidase enzyme activity in 20 children treated with valproic acid, in 10 children treated with carbamazepine, and ...in 75 age- and sex-matched healthy controls. There were no significant differences in the serum levels of biotin, and biotinidase enzyme activity between the patients treated with valproic acid, the patients treated with carbamazepine, and the control group. Zinc serum levels were lower in the patients treated with valproic acid and with carbamazepine than in the control group, but within the normal range. Hair loss was observed in 3 patients treated with valproic acid, with normal serum levels of biotin, zinc, and biotinidase activity, and the alopecia disappeared with the oral administration of biotin (10 mg/d) in 3 months. These results suggest that the treatment with valproic acid does not alter the serum levels of biotin, zinc, and biotinidase enzyme activity.
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