We present a case of anion gap euglycemic diabetic ketoacidosis (EuDKA) in a patient with COVID-19 infection. Patients with diabetes mellitus are at increased risk of severe illness, and ...hyperglycaemia is associated with higher morbidity and mortality in patients infected with COVID-19.
A 76-year-old male with diabetes mellitus treated with SGLT2 inhibitor tested positive for COVID-19 infection on day 3 after his admission. In the emergency room he had a high anion gap metabolic acidosis and a blood glucose of 248 mg/dl. His urine tested strongly positive for ketones. A diagnosis of euglycemic diabetic ketoacidosis was made and he was treated with intravenous insulin and normal saline; his antidiabetic medications were stopped. His metabolic acidosis gradually resolved, and he was discharged.
Euglycemic diabetic ketoacidosis is a rare complication of COVID-19 infection. It is defined by the American Diabetes Association as the triad of anion gap metabolic acidosis with arterial pH <7.3, serum bicarbonate <18 mmol/l and ketonuria or ketonemia. It is a life-threatening complication which usually occurs in type 1 diabetes mellitus patients but may also occur in type 2 diabetes mellitus patients. As described earlier, it is associated with hyperglycaemia but if blood glucose is low or near normal but <250 mg/dl it is then named euglycemic diabetic ketoacidosis. Patients treated with SGLT2 inhibitors are at increased risk of euglycemic diabetic ketoacidosis.
COVID-19 infection precipitated euglycemic diabetic ketoacidosis in our patient. SGLT2 inhibitors must be stopped when this adverse reaction occurs. As their use increases, the risk of this adverse reaction is higher as well. Their prescription should be restricted to trained physicians who are able to educate their patients and treat them appropriately in situations that may arise.
COVID-19 infected patients are at increased risk of developing diabetic ketoacidosis or euglycemic ketoacidosis when treated with SGLT-2 inhibitors.It is practical to discontinue the drug at the onset of any symptoms consistent with acute infection to prevent the development of euglycemic diabetic ketoacidosis.
OBJECTIVESBlood pressure (BP) changes are steeper in hypertensive than in normotensive individuals, whereas an increased rate of BP fluctuations is associated with medial hypertrophy of the carotid ...arteries. We evaluated the association between the rate of BP variation derived from ambulatory blood pressure monitoring (ABPM) data analysis and left ventricular mass (LVM).
METHODSABPM and echocardiographic measurements of LVM were performed in 365 normotensive, 185 white-coat hypertensive (WCH) and 448 uncomplicated hypertensive individuals.
RESULTSThe daytime and night-time rate of systolic blood pressure (SBP) and diastolic BP variation were significantly higher in hypertensive than in normotensive (P < 0.001) and WCH (P < 0.05) individuals. In the entire study population multiple linear regression models revealed independent determinants of LVM in the following rank orderbody mass index (β + 0.266, P < 0.001), daytime SBP (β + 0.264, P < 0.001), male sex (β +0.220, P < 0.001), age (β + 0.203, P < 0.001), daytime heart rate (HR; β − 0.191, P < 0.001), daytime rate of SBP variation (β + 0.167, P < 0.001), and SBP dipping (β − 0.132, P < 0.001). A 0.1 mmHg/min increase in the daytime rate of SBP variation correlated with an increment of 7.087 g (95% confidence interval 4.775–9.399) in the LVM. The addition of the daytime rate of SBP variation in the multiple regression model for the prediction of LVM significantly increased the adjusted model R R change 0.024 (2.4%); P for change < 0.001.
CONCLUSIONSteeper BP variations may produce a greater stress on the left ventricular wall and may have an additive role to body habitus, BP and HR levels in the detection of cardiac hypertrophy. Target-organ damage in hypertensive patients, in addition to BP levels, dipping status and BP variability, may also be related to a steeper rate of BP oscillations.
In a recent study of our group with the acronym ACTIVATE, Bacillus Calmete-Guérin (BCG) vaccination reduced the occurrence of new infections compared to placebo vaccination in the elderly. Most ...benefit was found for respiratory infections. The ACTIVATE-2 study was launched to assess the efficacy of BCG vaccination against coronavirus disease 2019 (COVID-19). In this multicenter, double-blind trial, 301 volunteers aged 50 years or older were randomized (1:1) to be vaccinated with BCG or placebo. The trial end points were the incidence of COVID-19 and the presence of anti–severe acute respiratory syndrome coronavirus 2 (anti–SARS-CoV-2) antibodies, which were both evaluated through 6 months after study intervention. Results revealed 68% relative reduction of the risk to develop COVID-19, using clinical criteria or/and laboratory diagnosis, in the group of BCG vaccine recipients compared with placebo-vaccinated controls, during a 6-month follow-up (OR 0.32, 95% CI 0.13-0.79). In total, eight patients were in need of hospitalization for COVID-19: six in the placebo group and two in the BCG group. Three months after study intervention, positive anti–SARS-CoV-2 antibodies were noted in 1.3% of volunteers in the placebo group and in 4.7% of participants in BCG-vaccinated group. The ACTIVATE II trial did not meet the primary endpoint of the reduction of the risk for COVID-19 3 months after BCG vaccination; however, the secondary endpoint of the reduction of the risk for COVID-19 6 months after BCG vaccination was met. BCG vaccination may be a promising approach against the COVID-19 pandemic.
Toxic epidermal necrolysis (TEN) is a rare, severe cutaneous adverse drug reaction with average mortality 25–35%, especially among elderly multimorbid patients. Established therapeutic guidelines do ...not exist and controversies underlie many of the presently suggested treatment regimens. Herein we present the use of the recently described combination scheme of methylprednisolone (500 mg methylprednisolone bolus i.v.) followed by infliximab (5 mg/kg i.v.) and high-dose intravenous immunoglobulin (2 g/kg over 5 days) to treat an elderly, 74-year-old female patient with TEN (SCORTEN 3) within the premises of a district hospital. Already from the second day of hospitalization the skin condition markedly stabilized and the patient's status improved rapidly thereafter. She was discharged after 19 days in stationary care in excellent general condition and remained without any sequels 9 months afterwards. The present paper further supports the feasibility, efficacy, and safety of the proposed combination modality for the treatment of elderly patients with TEN, a population susceptible to more severe TEN.
Among the physiological variables whose diurnal profile is governed by circadian rhythmicity, plasma glucose concentrations, and arterial blood pressure constitute key elements of the physiological ...regulation of energy homeostasis. Evidence on their diurnal association derived from frequent measurements of both variables is, however, lacking in humans.
We investigated the relationship between blood pressure levels recorded by an ambulatory device and interstitial glucose concentrations on an outpatient basis, in patients with normal glucose tolerance (N=20), either normotensive (group A; N=10), or newly diagnosed with essential hypertension (group B; N=10).
In the population throughout the 24-h monitoring period, there was a significant positive correlation between interstitial glucose concentrations and systolic, diastolic, and mean 24-h blood pressure levels, which was retained in patients with hypertension compared with normotensive patients. In patients with newly diagnosed hypertension, interstitial glucose concentrations exhibit significant correlation to systolic blood pressure levels during the 24-h period, but no association with diastolic and mean blood pressure during the night, whereas the reverse is the case in patients with normal glucose tolerance and normal blood pressure.
Diurnal variations of continuously monitored interstitial glucose concentrations significantly associate with blood pressure levels in both normotensive and hypertensive humans, indicating a common pathway of circadian autoregulation, probably stemming from both central mechanisms and peripheral inputs. Such a pathway might underlie similar pathophysiological aberration in disease states such as the metabolic syndrome.
The extent of target-organ damage has been positively associated with the magnitude of blood pressure (BP) variability in essential hypertension. However, the clinical implications of the rate of BP ...changes have never been investigated. We evaluated the possible association between the 24-hour time rate of systolic blood pressure (SBP) variation derived from computerized analysis of ambulatory BP monitoring (ABPM) data and the extent of common carotid artery intima-media thickness (CCA-IMT) in normotensive (n=237) and in uncomplicated hypertensive subjects (n=284). No antihypertensive and lipid-lowering treatment had ever been administered in any of the 521 subjects who underwent ABPM on a usual working day. The time rate of SBP variation was computed as the first derivative of the SBP values against time. The 24-hour rate of SBP variation was significantly (p<0.001) higher in hypertensive (0.609mmHg/min, 95%CI:0.596–0.622) than in normotensive individuals (0.566mmHg/min, 95%CI:0.554–0.576) even after adjusting for baseline characteristics, day-night BP changes, 24-hour heart rate (HR), SBP- and HR variability. In the hypertensive subgroup, the multiple linear regression models revealed independent determinants of CCA-IMT in the following rank order: age (p<0.001), 24-hour time rate of SBP variation (p<0.001), smoking (p=0.002), male gender (p=0.008) and triglycerides (p=0.017). Age (p<0.001) and 24-hour time rate of SBP variation (p=0.015) were the only significant determinants of CCA-IMT in normotensive individuals. A 0.1mmHg/min increase in the 24-hour rate of SBP variation correlated to an increment of 0.024mm (95%CI:0.005–0.042) and 0.026mm (95%CI:0.013–0.040) in the CCA-IMT of the normotensive and hypertensive subjects respectively even after adjustment for all baseline characteristics and other ABPM parameters. Thus, the rate of BP fluctuations is greater in hypertensive patients and correlates to CCA intima-media thickening. These findings indicate that steeper BP variations may produce a greater stress on the vessel wall and consequently result in medial hypertrophy of the large arteries.
Hyperhomocysteinemia has been recognised as an independent cardiovascular risk factor, while statins have been reported to have pleiotropic effects other than lipid lowering. In our study we sought ...to evaluate the possible effect of short-term administration of simvastatin on homocysteine (Hcy) and other established serum proatherogenic and inflammatory markers in essential hypertensive patients. Our study population consisted of 18 untreated mild essential hypertensive patients (9 men, mean age: 51.2±10.9 years, office blood pressure = 149/96 mmHg). All subjects received simvastatin (40mg/day) for a period of 1 month. Venous blood samples were drawn before and after the period of treatment with simvastatin in order to evaluate lipid, lipoprotein-a (Lp-a), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), fibrinogen, uric acid, homocysteine, folic acid, vitamin B12, high sensitivity-CRP (hsCRP) levels, by standard methodology. For the pooled population BMI was 27.2±3.6 kg/m2, left ventricular mass index was 106±35.1 g/m2, relative wall thickness was 0.45±0.07 and hsCRP levels were 1.5±0.3 mg/l. After 1 month on simvastatin, there was a significant reduction in total cholesterol (215.1±40.7 vs 156.0±29.2 mg/dl, p<0.001), triglycerides (114.1±30.9 vs 89.6±27.8 mg/dl, p<0.05), LDL (141.4±29 vs 89.6±21.6 mg/dl, p<0.001), ApoB (101.6±19.2 vs 71.8±15 mg/dl, p<0.001), uric acid (5.8±1.2 vs 5.4±1.1 mg/dl, p<0.05), homocysteine (13.6±7.3 vs 12.7±7.4 μmol/l, p<0.05). In all subjects, apoA1 and hs-CRP did not exhibit any statistically significant attenuation (p=NS, for all cases). Moreover, the reduction of Hcy serum levels was not correlated with the observed reductions in total cholesterol, triglycerides, LDL, ApoB and uric acid values (p=NS, for all cases). Even in newly diagnosed essential hypertensive subjects, short-term administration of simvastatin resulted in a significant and independent attenuation of Hcy serum levels. These findings may elucidate the diverse pathophysiological mechanisms by which statins reduce cardiovascular risk, in this setting.
Statins have been reported to improve blood pressure control in essential hypertensive subjects via diverse pathophysiological mechanisms, while salt sensitivity is an emerging cardiovascular risk ...factor. In this study, we sought to investigate the possible effects of short-term administration of simvastatin on blood pressure levels in salt sensitive and salt resistant essential hypertensive subjects. Eighteen untreated mild essential hypertensive patients (9 men, age 51.2±10.9 years) were screened for salt sensitivity by means of an established protocol. All subjects underwent 24h ambulatory BP monitoring before and after 1 month of treatment with simvastatin (40mg/day). Venous blood samples were drawn before and after statin administration period for determination of lipid, lipoprotein-a, apolipoprotein A1 and apolipoprotein B levels. For the pooled population BMI was 27.2±3.6 kg/m2, left ventricular mass index was 106±35.1 g/m2 and relative wall thickness was 0.45±0.07. Four patients were classified as salt sensitive (SS) (2 men, 60±9 years), while 14 were salt resistant (SR) (7 men, 60±10 years). After 1 month on simvastatin, only SS patients, presented significant reductions in office systolic BP (155±12.9 vs 130±18.2 mmHg, p<0.05), 24-h diastolic BP (85.9±5.7 vs 76.3±4.3 mm Hg, p<0.05), 24-h mean BP (104.4±5.1 vs 93.3±7.5 mm Hg, p<0.05), daytime diastolic BP (89.1±7.6 vs 78.9±6 mm Hg, p<0.05), daytime mean BP (107.5±8.5 vs 95.1±8.3 mm Hg, p<0.05), while patients in the SR group did not exhibit any significant reduction in 24h BP levels (p=NS). Moreover, there was no correlation between the reductions of 24h BP in the SS group and the reductions of the lipid parameters (p=NS). In newly diagnosed essential hypertensive subjects, short-term administration of simvastatin resulted in a significant attenuation of BP values in salt sensitive hypertensives, independently of lipid lowering, suggesting a possible link between salt sensitivity and the pleiotropic mechanisms of statins action. These findings suggest that salt sensitive patients may benefit more from the pleiotropic effects of statins, in the same setting.
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