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Diagnostics (Basel, Switzerland) Jul 2023Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes mellitus and can lead to patient demise if not immediately treated. From the recent... (Review)
Review
BACKGROUND
Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes mellitus and can lead to patient demise if not immediately treated. From the recent literature, the diabetic ketoacidosis mortality rate, depending on age, is 2-5%. Insulin discontinuation and infection remain the two most common triggers for diabetic ketoacidosis. About 50% of cases of ketoacidosis result from bacterial infections like urinary tract infections and pneumonia. It is also important to diagnose the presence of infection in diabetic ketoacidosis patients to prevent the excessive use of antibiotics, which may lead to antibiotic resistance. Although performing bacterial culture is confirmatory for the presence or absence of bacterial infection, the time required to obtain the result is long. At the same time, emergency treatment needs to be started as early as possible.
METHODS
This narrative review examines various septic markers to identify the appropriate tools for diagnosis and to distinguish between diabetic ketoacidosis with and without infection. Electronic databases were searched using the Google engine with the keywords "Diabetes Mellitus", "Diabetic Ketoacidosis", "Infection with Diabetic Ketoacidosis", "biomarkers for infection in Diabetic Ketoacidosis", "Procalcitonin", "Inflammatory cytokines in DKA", "Lactic acidosis in DKA", and "White blood cell in infection in DKA".
RESULTS
This narrative review article presents the options for diagnosis and also aims to create awareness regarding the gravity of diabetic ketoacidosis with infection and emphasizes the importance of early diagnosis for appropriate management. Diabetes mellitus is a clinical condition that may lead to several acute and chronic complications. Acute diabetic ketoacidosis is a life-threatening condition in which an excess production of ketone bodies results in acidosis and hypovolemia. Infection is one of the most common triggers of diabetic ketoacidosis. When bacterial infection is present along with diabetic ketoacidosis, the mortality rate is even higher than for patients with diabetic ketoacidosis without infection. The symptoms and biomarkers of diabetic ketoacidosis are similar to that of infection, like fever, C reactive protein, and white blood cell count, since both create an environment of systemic inflammation. It is also essential to distinguish between the presence and absence of bacterial infection to ensure the appropriate use of antibiotics and prevent antimicrobial resistance. A bacterial culture report is confirmatory for the existence of bacterial infection, but this may take up to 24 h. Diagnosis needs to be performed approximately in the emergency room upon admission since there is a need for immediate management. Therefore, researching the possible diagnostic tools for the presence of infection in diabetic ketoacidosis patients is of great importance. Several of such biomarkers have been discussed in this research work.
PubMed: 37510185
DOI: 10.3390/diagnostics13142441 -
Pediatric Nephrology (Berlin, Germany) Apr 2024The last decade has been characterized by exciting findings on eu- or hypoglycemic ketosis and ketoacidosis. This review emphasizes the following five key points: 1.... (Review)
Review
The last decade has been characterized by exciting findings on eu- or hypoglycemic ketosis and ketoacidosis. This review emphasizes the following five key points: 1. Since the traditional nitroprusside-glycine dipstick test for urinary ketones is often falsely negative, the blood determination of β-hydroxybutyrate, the predominant ketone body, is currently advised for a comprehensive assessment of ketone body status; 2. Fasting and infections predispose to relevant ketosis and ketoacidosis especially in newborns, infants, children 7 years or less of age, and pregnant, parturient, or lactating women; 3. Several forms of carbohydrate restriction (typically less than 20% of the daily caloric intake) are employed to induce ketosis. These ketogenic diets have achieved great interest as antiepileptic treatment, in the management of excessive body weight, diabetes mellitus, and in sport training; 4. Intermittent fasting is more and more popular because it might benefit against cardiovascular diseases, cancers, neurologic disorders, and aging; 5. Gliflozins, a new group of oral antidiabetics inhibiting the renal sodium-glucose transporter 2, are an emerging cause of eu- or hypoglycemic ketosis and ketoacidosis. In conclusion, the role of ketone bodies is increasingly recognized in several clinical conditions. In the context of acid-base balance evaluation, it is advisable to routinely integrate both the assessment of lactic acid and β-hydroxybutyrate.
Topics: Infant, Newborn; Child; Female; Humans; Hypoglycemic Agents; Diabetic Ketoacidosis; 3-Hydroxybutyric Acid; Lactation; Ketosis; Ketone Bodies
PubMed: 37584686
DOI: 10.1007/s00467-023-06115-5 -
Diabetic Medicine : a Journal of the... Jun 2024In tackling rising diabetes-related emergencies, the need to understand and address emergency service usage by people with type 1 diabetes is vital. This review aimed to... (Review)
Review
AIMS
In tackling rising diabetes-related emergencies, the need to understand and address emergency service usage by people with type 1 diabetes is vital. This review aimed to quantify current trends in presentations for type 1 diabetes-related emergencies and identify public health strategies that reduce the frequency of diabetes-related emergencies and improve glycaemic management.
METHODS
Medline (OVID), Cochrane and CINAHL were searched for studies published between 2000 and 2023, focusing on people with type 1 diabetes, severe hypoglycaemia and/or diabetic ketoacidosis, and ambulance and/or emergency department usage. There were 1313 papers identified, with 37 publications meeting review criteria.
RESULTS
The incidence of type 1 diabetes-related emergencies varied from 2.4 to 14.6% over one year for hypoglycaemic episodes, and between 0.07 and 11.8 events per 100 person-years for hyperglycaemic episodes. Notably, our findings revealed that ongoing diabetes education and the integration of diabetes technology, such as continuous glucose monitoring and insulin pump therapy, significantly reduced the incidence of these emergencies. However, socio-economic disparities posed barriers to accessing these technologies, subsequently shifting the cost to emergency healthcare and highlighting the need for governments to consider subsidising these technologies as part of preventative measures.
CONCLUSIONS
Improving access to continuous glucose monitoring and insulin pump therapy, in combination with ongoing diabetes education focusing on symptom recognition and early management, will reduce the incidence of diabetes-related emergencies. Concurrent research assessing emergency healthcare usage patterns during the implementation of such measures is essential to ensure these are cost-effective.
PubMed: 38923618
DOI: 10.1111/dme.15384 -
Expert Opinion on Drug Safety Jan 2024There is limited evidence on the safety of sodium-glucose co-transporter-2 inhibitor (SGLT2i) use in the real world of China. We conducted this two-center, retrospective...
BACKGROUND
There is limited evidence on the safety of sodium-glucose co-transporter-2 inhibitor (SGLT2i) use in the real world of China. We conducted this two-center, retrospective study to assess the incidence rate and risk factors of Dapagliflozin-associated DK/DKA among patients with type 2 diabetes mellitus (T2DM) in China.
RESEARCH DESIGN AND METHODS
Patients with T2DM treated with Dapagliflozin in Shanghai General Hospital were included in this retrospective analysis. Univariate and multivariate logistic regression was performed, and odds ratio (OR) and 95% confidence interval (CI) were calculated to identify the influencing factors associated with the occurrence of DK/DKA.
RESULTS
A total of 1985 T2DM patients received Dapagliflozin for the first time were included. The prevalence of DK and DKA was 2.47% and 0.35%, respectively. Multivariate logistic regression identified age <45 years [OR = 2.99, 95% CI (1.45-6.17)], concomitant use of Acarbose [OR = 2.18, 95% CI (1.06-3.38)], Metformin [OR = 1.84, 95% CI (1.01-3.38)], and Insulin [OR = 1.93, 95% CI (1.02-3.66)] as participating factors for DK/DKA. The 1:4 matched subset sensitivity analysis further confirmed the risk factors of Dapagliflozin-associated DK/DKA.
CONCLUSIONS
Age less than 45 years, concomitant use of Acarbose and insulin were risk factors for Dapagliflozin-associated DK/DKA. Clinicians should watch out for high-risk features among patients with SGLT2i prescription.
Topics: Humans; Middle Aged; Diabetic Ketoacidosis; Diabetes Mellitus, Type 2; Retrospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Acarbose; China; Risk Factors; Insulin; Benzhydryl Compounds; Glucosides
PubMed: 37947121
DOI: 10.1080/14740338.2023.2275704 -
Journal of Hazardous Materials Oct 2023The associations between air pollution and diabetes mortality of different subtypes and complications were largely unclear. We performed an individual-level,...
The associations between air pollution and diabetes mortality of different subtypes and complications were largely unclear. We performed an individual-level, time-stratified case-crossover study among over 0.9 million diabetes deaths from all administrative regions of Chinese mainland during 2013-2019. Daily concentrations of fine particles (PM), coarse particles (PM), nitrogen dioxide (NO) and ozone (O) were obtained for each decedent using high-resolution prediction models. Conditional logistic regression models were utilized to analyze the data. Each interquartile range increment in PM, PM, NO and O concentrations on lag 0-2 d increased the risks of overall diabetes mortality by 2.81 %, 1.92 %, 3.96 % and 2.15 %, respectively. Type 2 diabetes had stronger associations with air pollution than type 1 diabetes. Air pollutants were associated with diabetic ketoacidosis and diabetic nephropathy, but not other complications. The exposure-response curves were approximately linear with a plateau at higher concentrations of PM, PM, and NO, while the associations for O appear to be statistically significant beyond 60 μg/m. This nationwide study reinforces the evidence of higher risks of acute diabetic events following short-term air pollution exposure. We identified differential effects of air pollutants on various subtypes and complications of diabetes, which require further mechanistic investigations.
Topics: Humans; Air Pollutants; Cross-Over Studies; Diabetes Mellitus, Type 2; Nitrogen Dioxide; Particulate Matter
PubMed: 37696209
DOI: 10.1016/j.jhazmat.2023.132412 -
Diabetes Technology & Therapeutics Oct 2023Multiple daily injection insulin therapy frequently fails to meet hospital glycemic goals and is prone to hypoglycemia. Automated insulin delivery (AID) with remote...
Multiple daily injection insulin therapy frequently fails to meet hospital glycemic goals and is prone to hypoglycemia. Automated insulin delivery (AID) with remote glucose monitoring offers a solution to these shortcomings. In a single-arm multicenter pilot trial, we tested the feasibility, safety, and effectiveness of the Omnipod 5 AID System with real-time continuous glucose monitoring (CGM) for up to 10 days in hospitalized patients with insulin-requiring diabetes on nonintensive care unit medical-surgical units. Primary endpoints included the proportion of time in automated mode and percent time-in-range (TIR 70-180 mg/dL) among participants with >48 h of CGM data. Safety endpoints included incidence of severe hypoglycemia and diabetes-related ketoacidosis (DKA). Additional glycemic endpoints, CGM accuracy, and patient satisfaction were also explored. Twenty-two participants were enrolled; 18 used the system for a total of 96 days (mean 5.3 ± 3.1 days per patient), and 16 had sufficient CGM data required for analysis. Median percent time in automated mode was 95% (interquartile range 92%-98%) for the 18 system users, and the 16 participants with >48 h of CGM data achieved an overall TIR of 68% ± 16%, with 0.17% ± 0.3% time <70 mg/dL and 0.06% ± 0.2% time <54 mg/dL. Sensor mean glucose was 167 ± 21 mg/dL. There were no DKA or severe hypoglycemic events. All participants reported satisfaction with the system at study end. The use of AID with a disposable tubeless patch-pump along with remote real-time CGM is feasible in the hospital setting. These results warrant further investigation in randomized trials.
Topics: Humans; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Feasibility Studies; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Infusion Systems; Insulin, Regular, Human; Pilot Projects
PubMed: 37578778
DOI: 10.1089/dia.2023.0304 -
Tropical Medicine & International... Sep 2023Diabetic ketoacidosis (DKA) is a common, severe and often fatal complication of diabetes. This study aimed to investigate the clinical characteristics and precipitants...
OBJECTIVES
Diabetic ketoacidosis (DKA) is a common, severe and often fatal complication of diabetes. This study aimed to investigate the clinical characteristics and precipitants of DKA, as well as factors associated with DKA severity in Ghanaian patients.
METHODS
Cross-sectional study of the medical records of all 70 adult patients >18 years managed for DKA in the adult emergency room of Korle-Bu Teaching Hospital in Ghana from March 2019 to July 2019. DKA diagnosis was based on hyperglycaemia >11.0 mmol/L, ketonuria (more than 2+) plus acidaemia of (pH < 7.3) or bicarbonate (HCO ) <15.0 mmol/L. However, when serum bicarbonate and pH were not available, clinical signs of acidosis, for example, Kussmaul breathing aided in the diagnosis. DKA severity was assessed based on the Joint British Diabetes Societies (JBDS) guidelines of factors suggestive of severe DKA. Multivariable logistic regression was used to determine the factors associated with DKA severity. Odds ratio and 95% confidence interval for factors associated with DKA severity were determined.
RESULTS
The mean (±standard deviation) age, diabetes duration and blood sugar at admission were 44.06 (±16.23) years, 7.19 (±6.04) years and 26.37 (±6.70) mmol/L, respectively. Females comprised 51.4% of the study population. The most common presenting symptoms were generalised weakness (30.0%) and fever (14.3%). The major precipitants were infection (70.0%) and non-compliance (22.9%). Overall, 71.4% of participants had features suggestive of severe DKA. In a multivariable regression model, Type 2 diabetes was associated with over fourfold decreased odds of severe DKA (OR 0.23, 95% CI [0.07-0.76], p = 0.016). Patient education on prevention of DKA was documented for only 18.6% of patients before being discharged.
CONCLUSION
In this study, more than 70% of the study participants had features suggestive of severe DKA, with infection being the most common precipitant of DKA. 51.4% of patients had Type 2 diabetes which was associated with a statistically lower risk of severe DKA. Female sex tended to be positively associated with DKA severity. In a setting where the venous/arterial pH and bicarbonate levels may be inaccessible and/or unaffordable, using clinical features as found in the JBDS guidelines may help categorise patients and escalate care when needed. Indeed it may be useful to validate the use of the JBDS criteria for use in such settings.
Topics: Adult; Humans; Female; Middle Aged; Male; Diabetic Ketoacidosis; Diabetes Mellitus, Type 2; Ghana; Cross-Sectional Studies; Tertiary Care Centers; Bicarbonates
PubMed: 37537727
DOI: 10.1111/tmi.13919 -
Clinical Diabetes and Endocrinology Jun 2024Diabetes presenting in young adults is often challenging to classify. Diabetic ketoacidosis is typically seen in autoimmune type 1 diabetes mellitus and more rarely in... (Review)
Review
Diabetic ketoacidosis in an adult with beta-ketothiolase deficiency (BKD) involving a novel ACAT1 variant : first report of established diabetes in BKD and a review of the literature.
BACKGROUND
Diabetes presenting in young adults is often challenging to classify. Diabetic ketoacidosis is typically seen in autoimmune type 1 diabetes mellitus and more rarely in young onset type 2 diabetes mellitus. Beta-ketothiolase deficiency (BKD) is a rare autosomal recessive condition affecting isoleucine catabolism and ketone body metabolism. BKD typically manifests in childhood as recurrent episodes of ketoacidosis, the frequency of which tends to reduce with age. There is a paucity of data with respect to the co-existence of persistent dysglycemia with BKD.
CASE PRESENTATION AND LITERATURE REVIEW
We present a novel case of diabetes presenting as diabetic ketoacidosis in a 34-year-old man with BKD, with genetically confirmed compound heterozygosity for variants in ACAT1, including a novel ACAT1 c.481T>C, p.(Tyr161His) variant. Diabetes in people with BKD presents unique diagnostic and management challenges. To further contextualize our findings, we conducted a comprehensive narrative review of the existing literature with respect to dysglycemia in those with BKD, especially in adulthood. There are no existing reports describing diabetes in adults with BKD. Stress hyperglycemia is not uncommon when children with BKD are acutely unwell, with several pediatric case reports describing short-lived hyperglycemia but normal HbA1c measurements during metabolic crises (indicating the absence of persistent hyperglycemia).
CONCLUSIONS
This is the first report of diabetic ketoacidosis in an adult with BKD, with an elevated HbA1c consistent with persistent hyperglycemia. This case highlights the importance of checking HbA1c in people with BKD and hyperglycemia in order to uncover potential coexisting diabetes, facilitating timely management and preventing complications. Increased reporting on the longitudinal outcomes of those with rare metabolic disorders is essential for identifying potential associations with conditions like diabetes.
PubMed: 38853254
DOI: 10.1186/s40842-024-00174-9 -
Biomarkers in Medicine Nov 2023An early prediction of infection is challenging in diabetic ketoacidosis (DKA). This prospective cohort study aimed to assess effectiveness of various sepsis screening...
An early prediction of infection is challenging in diabetic ketoacidosis (DKA). This prospective cohort study aimed to assess effectiveness of various sepsis screening tools in predicting infections and prognosis in DKA. Among 141 cases, infection (44.0%) was the commonest precipitating factor. A Sequential Organ Failure Assessment score ≥4 showed high specificity (82.28%) and high positive likelihood ratio (2.64) but limited sensitivity (46.77%). Conversely, Systemic Inflammatory Response Syndrome ≥2 exhibited good sensitivity (95.16%) but a high false-positive rate (84.28%). National Early Warning Score ≥7 and Quick Sequential Organ Failure Assessment ≥2 had low sensitivity and specificity. These sepsis tools also demonstrated low prognostic accuracy for mortality. Sepsis screening tools have limited predictive accuracy for infections and mortality in DKA.
Topics: Humans; Diabetic Ketoacidosis; Precipitating Factors; Prospective Studies; Organ Dysfunction Scores; Prognosis; Sepsis; Retrospective Studies; Hospital Mortality; Diabetes Mellitus
PubMed: 38214173
DOI: 10.2217/bmm-2023-0574 -
Diabetes & Metabolic Syndrome Sep 2023The effectiveness of standard treatment for diabetic ketoacidosis (DKA) in "euglycemic DKA" (EuDKA, blood glucose (BG) ≤ 250 mg/dL) was evaluated with respect to...
OBJECTIVE
The effectiveness of standard treatment for diabetic ketoacidosis (DKA) in "euglycemic DKA" (EuDKA, blood glucose (BG) ≤ 250 mg/dL) was evaluated with respect to the time to correction of BG ≤ 200 mg/dL, anion gap (AG)≤12 mmol/L, and serum bicarbonate [HCO3] ≥18 mmol/L.
METHODS
Data were retrieved from an electronic health record (EPIC) for "diabetic ketoacidosis." Patients were categorized by initial BG as EuDKA, middle range DKA (MrDKA, >250 < 600 mg/dL) and hyperosmolar DKA (HyperDKA ≥600 mg/dL).
RESULTS
There were 56 patients (27men, 29women; age 45.8 ± 15.6 (SD) years. The initial 8-h insulin infusion rate (0.05 ± 0.02, 0.09 ± 0.03, 0.14 ± 0.05units/kg/h, p < 0.001) and the time to correction of BG (3.4 ± 1.9, 6.1 ± 2.9 and 9.6 ± 3.9 h, p < 0.001), differed for EuDKA, MrDKA and HyperDKA. There were no differences in the time to correction of AG or [HCO3]. The earlier time to correction of BG in EuDKA resulted in paradoxical longer lag times for correction of [HCO3] (p = 0.003) and AG (p = 0.048). Changes in BG, AG and [HCO3] correlated with insulin infusion rates of 0.08-0.1units/kg/h whereas in EuDKA the insulin infusion rate was 0.05 ± 0.02 units/kg/h.
CONCLUSION
In EuDKA, correlation analyses suggest that higher glucose and insulin infusion rates than what would be projected for the level of blood glucose are required to reverse ketoacidosis. Prospective trials are required to optimize the levels of glucose and insulin infusions in EuDKA.
PubMed: 37651890
DOI: 10.1016/j.dsx.2023.102848