Diabetes mellitus is a long-term metabolic disease marked by consistently elevated blood glucose levels. Diabetic ketoacidosis is the medical consequence of diabetes mellitus that has the highest attributed fatality rate. Socioeconomically differences affect how long it takes to recover from diabetic ketoacidosis. A few research were carried out in Africa to demonstrate how long diabetic ketoacidosis takes to recover. However, the pooled median recovery time and predictors of diabetic ketoacidosis have not been studied in Africa. Thus, determine the pooled median recovery time and predictors of diabetic ketoacidosis in Africa was the aim of this systematic review and meta-analysis.

To find available publications, a number of databases were analyzed, including PubMed, Science Direct, Cochrane, Hinari, Google Scholar, grey literature, and articles from various university repository sites. Microsoft Excel version 13 was used to extract and sort the data before exporting it to STATA/MP 17.0 for analysis. The quality of each study was evaluated using the Newcastle-Ottawa Scale. A 95 percent confidence interval Der Simonian random-effects model was employed to investigate the pooled recovery time of diabetic ketoacidosis. Publication bias and heterogeneity were assessed using the Egger's test and I2. Both meta-regression and subgroup analysis were used to determine the potential source of heterogeneity. Statistical significance was defined as P-values below 0.05.

The pooled median recovery time for diabetic ketoacidosis in Africa was 38 h (95 percent CI: 33-43 h), according to this comprehensive review and meta-analysis. Significant heterogeneity is evident when looking at the Galbraith plot with I2 = 100 % (p < 0.001). Research conducted after 2020 revealed that diabetic ketoacidosis has a long recovery time of 40 h (95 percent CI: 3-77 h). However, research with fewer than 300 participants showed that diabetic ketoacidosis recovered more quickly: 18 h (95 percent confidence interval: 12-24 h).

Among patients with diabetic ketoacidosis in Africa, the pooled median recovery time was lengthy. The recovery time from diabetic ketoacidosis was influenced by a number of factors, including the severity of the diabetic ketoacidosis, the delay in starting therapy, and the length of time the patient had diabetes mellitus, and elevated blood glucose levels. Diabetic ketoacidosis recovery time can be shortened by altering these factors.

We previously implemented the subcutaneous (SQ) insulin in diabetic ketoacidosis (DKA) (SQuID) protocol, demonstrating safe, effective treatment of low to moderate (LTM) severity DKA in a non-intensive care unit setting. SQuID replaces intravenous (IV) insulin with SQ injections and reduces glucose checks from hourly to every 2 hours. We are not aware of any data on patient satisfaction with treatment in DKA. Our objective was to compare satisfaction in patients treated with IV insulin to that in patients treated with the SQ protocol.

We conducted a cross-sectional study in an urban academic hospital (March 2023 to March 2024) of emergency department patients treated for LTM DKA with SQ or IV insulin. Patients were contacted by phone in the hospital after the resolution of DKA. We used the validated 21-item Diabetic Treatment Satisfaction Questionnaire-Inpatient tool (DTSQ-IP) using 7-tier Likert-style options (0 = negative; 6 = positive) to assess patient satisfaction with treatment. We computed the DTSQ-IP composite treatment satisfaction score (using 15 of the 21 items), assessing differences between groups.

Of the 60 patients contacted, 52 (87%) completed the questionnaire. Median DTSQ-IP satisfaction scores for SQuID and IV insulin patients were 86.0 (IQR, 79.0, 88.0) and 81.0 (IQR, 77.0, 88.0), respectively. We found no difference in satisfaction between groups (difference 5.0; 95% CI, -3.0, 10.0).

In this single-center study, patient satisfaction with DKA care was high, with no differences observed between patients treated with SQ vs IV insulin protocols. This is the first study we are aware of on patient satisfaction with treatment in DKA or treatment with SQ insulin. Though the sample size is small, these findings suggest that patient satisfaction should not represent a barrier to the implementation of SQ protocols for LTM severity DKA.

Diabetic ketoacidosis (DKA) is a severe and life-threatening condition associated with diabetes mellitus, characterized by profound metabolic acidosis, ketosis, elevated blood glucose levels, and disturbances in electrolytes. While these are the typical features, DKA can also lead to rare but potentially life-threatening complications such as cerebral venous thrombosis. The hypercoagulable state associated with DKA, exacerbated by dehydration and diabetes itself, promotes coagulation. We present the case of a 33-year-old man with no significant medical history, who was admitted with acute symptoms of lethargy, vomiting, and chills. He was diagnosed with DKA and managed with intravenous insulin, fluid resuscitation, and electrolyte correction. During recovery, he developed meningeal symptoms, and imaging revealed a cerebral venous thrombosis. Anticoagulation therapy led to significant clinical improvement. This case highlights the importance of recognizing rare thrombotic complications in DKA such as cerebral thrombosis. It highlights the need for prompt management and further investigation into the role of anticoagulation therapy in DKA.

We previously implemented the SQuID protocol (subcutaneous insulin in diabetic ketoacidosis [DKA]) demonstrating safe, effective treatment of low- to moderate-severity DKA in a non-intensive care unit setting. Since success and sustainability of interventions rely on staff buy-in, we assessed acceptability of SQuID among emergency department (ED) and inpatient clinicians.

We conducted a cross-sectional study in an urban academic hospital (March 2023-November 2023), surveying ED nurses (RNs) and physicians (MDs) and floor RNs and MDs treating patients on SQuID via emailed survey links. Clinicians could only take the survey once. We used Sekhon's Theoretical Framework of Acceptability, validated for staff acceptability of a new intervention, assessing eight domains with 5-point Likert responses. Clinicians were asked about prior experience with SQuID, and we assessed ED MD and RN preference (SQuID vs. intravenous [IV] insulin). Surveys included free-text boxes for comments. We present descriptive statistics including proportions with 95% confidence interval and medians with interquartile ranges (IQRs) and conducted thematic analysis of free-text comments.

Our overall response rate (107/133) was 80% (34/42 ED RNs, 13/16 floor RNs, 47/57 ED MDs, 13/17 floor MDs), with first-time users of SQuID ranging from 7.7% (hospitalist MDs) to 35.3% (ED RNs) of participants. ED clinicians preferred SQuID over IV insulin (67% vs. 12%, 21% no preference). Acceptability was high across all domains and clinician types (median 4, IQR 4-5). Overall percentage of positive responses (4s and 5s) across domains was 92% (ED RNs [89%], floor RNs [89%], ED MDs [97%], floor MDs [87%]). We identified several themes among participant comments.

Acceptability was high across clinician types; 65% of ED clinicians preferred SQuID to IV insulin. Clinicians liked SQuID (affective attitude), found it easy to use (burden), were confident in its use (self-efficacy), felt that it improved outcomes (perceived effectiveness), found that it was fair to patients (ethicality), found that it made sense (intervention coherence), and found that it did not interfere with other activities (opportunity cost).

We previously demonstrated safe treatment of low- to moderate-severity (LTM) diabetic ketoacidosis (DKA) using the SQuID protocol (subcutaneous insulin in DKA) in a non-intensive care unit (ICU) observation setting, with decreased emergency department length of stay (EDLOS). Here, we expand eligibility to include sicker patients and admission to a regular medical floor and collected more detailed clinical data in a near-real-time fashion.

This is a real-world, prospective, observational cohort study in an urban academic hospital (March 4, 2023-March 4, 2024). LTM DKA patients were treated with IV insulin (floor or ICU) or on SQuID. We compare fidelity (time to glargine and dextrose-containing fluids), safety (rescue dextrose for hypoglycemia), effectiveness (time to anion gap closure, time on protocol), and operational efficiency (time to bed request, EDLOS, and ICU admission rate since implementation of the protocol).

Of 84 patients with LTM DKA, 62 (74%) of were treated with SQuID and 22 (26%) with IV insulin. Fidelity was high in both groups. Rescue dextrose was required in five (8%) versus four (18%) patients, respectively (difference 9%, -31% to 10%). Compared to the IV insulin group, time to anion gap was 1.4 h shorter (95% CI -3.4 to 0.2 h) and time on protocol was 10.4 h shorter (95% CI -22.3 to -5.0 h) in SQuID patients. Median EDLOS was lower in the SQuID cohort 9.8 h (IQR 6.0-13.6) than the IV floor cohort 18.3 h (IQR 13.4-22.0 h), but longer than the overall IV insulin cohort. Since inception of SQuID, ICU admission rate in LTM DKA has decreased from 54% to under 21%.

In this single-center study, we observed excellent fidelity, equivalent or superior safety, and clinical and operational effectiveness with SQuID compared to IV insulin. The SQuID protocol has become the de facto default pathway for treatment of LTM DKA. Since inception of SQuID, ICU admissions in LTM DKA have decreased 33%.

Background Diabetic ketoacidosis (DKA) is a common and serious complication of diabetes, often requiring hospitalization and intensive care. Fluid resuscitation is a cornerstone of DKA management, with traditional guidelines recommending isotonic normal saline (NS) for initial volume replacement. Recent studies, however, suggest that large volumes of NS may lead to undesirable outcomes such as hyperchloremic metabolic acidosis. This study investigates the effects of large-volume NS resuscitation on clinical outcomes in DKA management, comparing it to other fluids, such as lactated Ringers (LR). Objective To evaluate whether large-volume resuscitation with isotonic normal saline (NS) is associated with prolonged ICU length of stay (LOS), increased time on insulin infusion, and higher rates of non-anion gap metabolic acidosis in patients with DKA. Materials and methods This was a single-center, retrospective, observational study conducted at Naples Comprehensive Healthcare System. We reviewed electronic medical records of patients diagnosed with DKA, defined by pH <7.3, bicarbonate <18, and anion gap >12. The primary outcome was ICU LOS, and secondary outcomes included overall length of stay, insulin infusion duration after DKA resolution, and incidence of non-anion gap metabolic acidosis after DKA resolution. Patients were grouped by the amount of NS received during resuscitation: 0L, 1L, 2L, and ≥3L. Statistical analyses included analysis of variance (ANOVA), t-tests, and chi-square tests to compare outcomes between groups. Results A total of 109 patients were included in the study. The mean age was 51.34 years, and the cohort consisted of 43.1% females and 56.9% males. There was no significant difference in ICU LOS between patients who received 0L and 1L of NS. However, patients who received 2L (p=0.0249) and ≥3L (p=0.00065) had significantly longer ICU LOS compared to those who received 0L of NS. No significant difference in overall LOS was also observed across all groups (p=0.894). Patients who received ≥3L of NS had a significantly longer duration of insulin infusion compared to those who received 0L (p=0.0101) after DKA anion gap closure while a significant increase in the incidence of non-anion gap acidosis after DKA resolution was observed in patients receiving ≥2L of NS (p=0.0000). Conclusion This study suggests that large-volume resuscitation with isotonic NS in DKA patients is associated with increased ICU length of stay, prolonged insulin infusion, and a higher incidence of non-anion gap metabolic acidosis. These findings support the use of balanced crystalloids, such as lactated Ringers, for initial resuscitation in DKA patients, as they may reduce the risk of complications related to hyperchloremia and improve clinical outcomes. Further prospective studies are needed to confirm these findings and guide fluid management protocols in DKA.

To assess factors associated with serum phosphorus (P) and hypophosphatemia in children with type 1 diabetes mellitus (T1DM) treated for diabetic ketoacidosis (DKA).

Retrospective cohort.

Community-based PICU in a university-affiliated hospital.

Patients 1-20 years old with T1DM hospitalized for DKA from July 1, 2016, to July 31, 2022.

None.

We collected age, sex, duration of T1DM, conscious state at presentation, and most recent glycohemoglobin level. P was tested initially and then every 4 hours. Probability of hypophosphatemia and time to hypophosphatemia and hospital length of stay (LOS) were analyzed via binomial and linear mixed-effects regression analyses, respectively. A total of 852 DKA episodes occurred in 365 patients (46.3% female, median age 14.7 yr), of which 158 (18.5%) episodes were new-onset T1DM. Hypophosphatemia developed during 656 of 852 (77%) episodes, including 49 of 852 (5.8%) episodes of severe hypophosphatemia with median (interquartile range) onset 8.0 hours (4.7-11.9 hr) and 12.0 hours (8.1-17.6 hr), respectively, following initiation of therapy. Higher glycohemoglobin was associated with greater odds of hypophosphatemia (odds ratio [OR], 1.22; p < 0.001). However, lower odds of hypophosphatemia were associated with older age (OR, 0.89; p < 0.01), male (OR, 0.11; p = 0.01), longer T1DM duration (OR, 0.87; p < 0.001), and having initial normal conscious state (OR, 0.18; p < 0.01). Older age (3.0%/yr; p = 0.02), T1DM duration (4.1%/yr; p = 0.01), and initial serum P (23.4%/mg/dL; p < 0.001) were associated with later hypophosphatemia. LOS was shorter with increased T1DM duration (3.6%/yr; p < 0.001) and normal conscious state (33.1% shorter; p < 0.001), but longer with increasing glycohemoglobin (4.0%; p < 0.001). All patients survived with normal neurologic function.

Higher glycohemoglobin was associated with greater odds of hypophosphatemia and longer LOS. Older male, longer duration of T1DM, and conscious at admission were factors associated with lower odds of developing hypophosphatemia and with later onset when it occurred. Hypophosphatemia was associated with longer LOS.

This review discusses the challenges and controversies in the treatment of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). Key areas include the selection of intravenous (IV) fluids, insulin therapy, strategies for preventing and monitoring cerebral edema (CE) by managing hyperglycemia overcorrection, electrolyte replacement, timing of nutrition, use of IV sodium bicarbonate, and airway management in critically ill DKA patients. Isotonic normal saline remains the standard for initial fluid resuscitation, though balanced solutions have been shown to have faster DKA resolution. Current guidelines recommend using continuous IV insulin for DKA management after fluid status has been restored potassium levels have been achieved and subcutaneous (SQ) insulin is started only after the resolution of metabolic acidosis. In comparison, the British guidelines recommend using SQ insulin glargine along with continuous regular IV insulin, which has shown faster DKA resolution and shorter hospital stays compared to continuous IV insulin alone. Although rare, rapid overcorrection of hyperglycemia with fluids and insulin can lead to CE, seizures, and death. Clinicians should be aware of risk factors and preventive strategies for CE. DKA frequently involves multiple electrolyte abnormalities, such as hypokalemia, hypophosphatemia, and hypomagnesemia and regular monitoring is essential for DKA management. Early initiation of oral nutrition has been shown to reduce intensive care unit and overall hospital length of stay. For impending respiratory failure, Bilevel positive airway pressure is not recommended due to aspiration risks. Instead, intubation and mechanical ventilation, with monitoring and management of acid-base and fluid status, are recommended. The use of sodium bicarbonate is discouraged due to the potential for worsening ketosis, hypokalemia, and risk of CE. However, IV sodium bicarbonate can be considered if the serum pH falls below 6.9, or when serum pH is less than 7.2 and/or serum bicarbonate levels are below 10 mEq/L, pre-and post-intubation, to prevent metabolic acidosis and hemodynamic collapse that occurs from apnea during intubation. Managing DKA and HHS in critically ill patients includes using balanced IV fluid solutions to restore volume status, followed by continuous IV insulin, early use of SQ glargine insulin, electrolyte replacement, and monitoring, CE preventive strategies by avoiding hyperglycemia overcorrection, early nutritional support, and appropriate airway management.

A type 1 diabetes (T1D) diagnosis is often followed by a period of reduced exogenous insulin requirement, with acceptable glucose control, called partial clinical remission (pCR). Various criteria exist to define pCR, which is associated with better clinical outcomes. We aimed to develop formulae and a related online calculator to predict the probability of pCR at 3- and 12-months post-T1D diagnosis. We analysed data from 133 adults at their T1D diagnosis (mean ± SD age: 27 ± 6 yrs., HbA1c 11.1 ± 2.0 %, 98 ± 22 mmol/mol), 3- and 12-months later. All patients were enrolled in the prospective observational InLipoDiab1 study (NCT02306005). We compared four definitions of pCR: 1) stimulated C-peptide >300 pmol/l; 2) insulin dose-adjusted HbA1c ≤9 %; 3) insulin dose <0.3 IU/kg/24 h; and HbA1c ≤6.4 % (46 mmol/mol); and 4) insulin dose <0.5 IU/kg/24 h and HbA1c <7 % (53 mmol/mol). Using readily available demographics and clinical chemistry data exhaustive search methodology was used to model pCR probability. There was low concordance between pCR definitions (kappa 0.10). The combination of age, HbA1c, diastolic blood pressure, triglycerides and smoking at T1D onset predicted pCR at 12-months with an area under the curve (AUC) = 0.87. HbA1c, triglycerides and insulin dose 3-mths post-diagnosis had an AUC = 0.89. A related calculator for pCR in adult-onset T1D is available at http://www.bit.ly/T1D-partial-remission.

Diabetic ketoacidosis (DKA) is a life-threatening condition among diabetic patients characterized by metabolic anion gap (AG) acidosis of arterial pH <7.30, glucose >250 mg/dL, and positive ketones. The triggers for DKA can be infection, surgery, and, in reported cases, intraparenchymal hemorrhage (IPH). In rare cases of DKA, despite being in active ketoacidosis, glucose levels may be within normal or accepted range. Such a condition is called euglycemic DKA. It has been recently recognized in association with the use of sodium glucose co-transporter-2 (SGLT-2) inhibitors in the treatment of type 2 diabetes.

An 83-year-old male taking an SGLT-2 inhibitor (empagliflozin) for type 2 diabetes presented with an IPH. His laboratory studies revealed an elevated AG acidosis, an elevated beta hydroxybutyrate, and serum glucose levels within the acceptable range. Urine studies revealed elevated ketones and glucose. The diagnosis of euglycemic DKA was made, and the patient was treated with insulin and glucose infusions.

Like hyperglycemic ketoacidosis, euglycemic DKA requires prompt recognition and immediate aggressive medical therapy, but the diagnosis can be challenging, and the treatment using insulin in the setting of a normal glucose can be counterintuitive. Euglycemic DKA can often be missed in the setting of blood glucose not being elevated. Prompt recognition and treatment are critical for successful management.

Patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) can present with diabetic ketoacidosis (DKA) as the first manifestation. Differentiating types of newly diagnosed diabetes could provide appropriate long-term management. Therefore, we conducted this study to compare clinical characteristics and outcomes between initially diagnosed type 1 and type 2 diabetes mellitus patients presenting with DKA.

A retrospective study was conducted on adult patients who presented with DKA as the first diagnosis of diabetes in our tertiary hospital between January 2005 and December 2019. Demographic data, precipitating causes, laboratory investigations, treatment, and outcomes were obtained by chart review. The primary outcome was to compare the clinical characteristics of initially diagnosed patients with T1DM and T2DM who presented with DKA.

A total of 100 initially diagnosed diabetic patients who presented with DKA were analyzed (85 T2DM patients and 15 T1DM patients). Patients with T1DM were younger than patients with T2DM (mean age 33 ± 16.2 vs. 51 ± 14.5 years, p value < 0.001). Patients with T2DM had a higher body mass index, family history of diabetes, precipitating factors, plasma glucose, and lower renal function than those with T1DM. There was no difference in resolution time or DKA management between T1DM and T2DM patients. The overall mortality rate of DKA was 4%.

In this population, most adult patients who presented with DKA had T2DM. Older age, obesity, a family history of diabetes, and the presence of precipitating factors were strong predictors of T2DM. We can implement the same clinical management for DKA in both T1DM and T2DM patients. However, T2DM patients had longer hospitalization than T1DM patients. After DKA resolution for 12 months, more than half of patients with T2DM could discontinue insulin. Therefore, the accurate classification of the type of diabetes leads to appropriate treatment.

To describe reported cases of prolonged or relapsed ketoacidosis (KA) in adults with type 2 diabetes receiving treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors.

We performed a search of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System and medical literature, to identify our case series and to characterize cases of prolonged KA, relapsed KA, or persistent ketonemia, persistent ketonuria and/or persistent glucosuria in adults receiving SGLT2 inhibitors.

The FDA identified 29 unique cases of prolonged or relapsed KA, as well as related terms persistent ketonemia, persistent ketonuria, and persistent glucosuria, in patients receiving SGLT2 inhibitors through July 26, 2022. The patients ranged in age from 26 to 85 years. Treatment duration of KA ranged from 3 to 20 days. There were 7 cases of relapsed KA when insulin was reduced or transitioned to subcutaneous route. Arterial pH value was 7.0 or below in 4 patients, and the median pH was 7.1. Associated factors for prolonged or relapsed KA included surgery, decreased caloric intake, and ketogenic/carbohydrate restricted diet. A total of 62% of the patients were taking 3 or more glycemic control medications including the SGLT2 inhibitor. All patients with sufficient follow-up information recovered.

Although KA is a well-known risk associated with SGLT2 inhibitors, this case series demonstrated the potential for prolonged or recurrent KA events with serious outcomes. These cases informed updates to FDA's prescribing information to inform prescribers of this risk.

Background: Patients with diabetic ketoacidosis (DKA) are transitioned from intravenous (IV) to subcutaneous (SQ) insulin upon DKA resolution. Although an anion gap (AG) ≤12 mEq/L is recommended before transition to SQ insulin, there are limited data to support this threshold. Objective: To compare the rates of successful transitions to SQ insulin in patients with DKA with an AG ≤ 12 mEq/L versus > 12 mEq/L. Methods: Retrospective cohort study of adult critically ill patients with moderate to severe DKA between September 2019 and December 2022. The primary outcome was the success of insulin transition between patients transitioned with an AG ≤ 12 mEq/L and those transitioned with an AG > 12 mEq/L. Transition was considered successful if the AG did not increase above the value at transition at 24 hours and insulin infusion was not restarted. Secondary outcomes include the individual components of the primary outcome and ICU length of stay (LOS); safety outcomes included hypoglycemia and electrolyte derangements. Results: In total, 92 patients were included, with 43 patients transitioned at AG ≤ 12 mEq/L and 49 patients transitioned at AG > 12 mEq/L. Transition was unsuccessful in 3 patients (7%) with AG ≤ 12 mEq/L and 2 patients (4%) with AG > 12 mEq/L (P = .66). There was no difference in the incidence of the individual components of this outcome between groups or in safety outcomes. Conclusion: This retrospective study showed no difference in success of insulin transition between the groups. Larger studies are needed to evaluate the impact of treatment characteristics on transition success and patient outcomes.

This review discusses the importance of homeostasis with a particular emphasis on the acid-base (AB) balance, a crucial aspect of pH regulation in living systems. Two primary organ systems correct deviations from the standard pH balance: the respiratory system via gas exchange and the kidneys via proton/bicarbonate secretion and reabsorption. Focusing on kidney functions, we describe the complexity of renal architecture and its challenges for experimental research. We address specific roles of different nephron segments (the proximal convoluted tubule, the loop of Henle and the distal convoluted tubule) in pH homeostasis, while explaining the physiological significance of ion exchange processes maintained by the kidneys, particularly the role of bicarbonate ions (HCO3-) as an essential buffer system of the body. The review will be of interest to researchers in the fields of physiology, biochemistry and molecular biology, which builds a strong foundation and critically evaluates existing studies. Our review helps identify the gaps of knowledge by thoroughly understanding the existing literature related to kidney acid-base homeostasis.

It is widely acknowledged that the ketogenic diet (KD) has positive physiological effects as well as therapeutic benefits, particularly in the treatment of chronic diseases. Maintaining nutritional ketosis is of utmost importance in the KD, as it provides numerous health advantages such as an enhanced lipid profile, heightened insulin sensitivity, decreased blood glucose levels, and the modulation of diverse neurotransmitters. Nevertheless, the integration of the KD with pharmacotherapeutic regimens necessitates careful consideration. Due to changes in their absorption, distribution, metabolism, or elimination, the KD can impact the pharmacokinetics of various medications, including anti-diabetic, anti-epileptic, and cardiovascular drugs. Furthermore, the KD, which is characterised by the intake of meals rich in fats, has the potential to impact the pharmacokinetics of specific medications with high lipophilicity, hence enhancing their absorption and bioavailability. However, the pharmacodynamic aspects of the KD, in conjunction with various pharmaceutical interventions, can provide either advantageous or detrimental synergistic outcomes. Therefore, it is important to consider the pharmacokinetic and pharmacodynamic interactions that may arise between the KD and various drugs. This assessment is essential not only for ensuring patients' compliance with treatment but also for optimising the overall therapeutic outcome, particularly by mitigating adverse reactions. This highlights the significance and necessity of tailoring pharmacological and dietetic therapies in order to enhance the effectiveness and safety of this comprehensive approach to managing chronic diseases.

The clinical use of insulin to treat diabetes started just over 100 years ago. The past century has witnessed remarkable innovations in insulin therapy, evolving from animal organ extracts to bioengineered human insulins with ultra-rapid onset or prolonged action. Insulin delivery systems have also progressed to current automated insulin delivery systems. In this review, we discuss the history of insulin and the pharmacology and therapeutic indications for a variety of available insulins, especially newer analog insulins. We highlight recent advances in insulin pump therapy and review evidence on the therapeutic benefits of automated insulin delivery. As with any form of progress, there have been setbacks, and insulin has recently faced an affordability crisis. We address the challenges of insulin accessibility, along with recent progress to improve insulin affordability. Finally, we mention research on glucose-responsive insulins and hepato-preferential insulins that are likely to shape the future of insulin therapy.

The duration of hospitalization, especially in the intensive care unit (ICU), for patients with diabetic ketoacidosis (DKA) is influenced by patient prognosis and treatment costs. Reducing ICU length of stay (LOS) in patients with DKA is crucial for optimising healthcare resources utilization. This study aimed to establish a nomogram prediction model to identify the risk factors influencing prolonged LOS in ICU-managed patients with DKA, which will serve as a basis for clinical treatment, healthcare safety, and quality management research.

In this single-centre retrospective cohort study, we performed a retrospective analysis using relevant data extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Clinical data from 669 patients with DKA requiring ICU treatment were included. Variables were selected using the Least Absolute Shrinkage and Selection Operator (LASSO) binary logistic regression model. Subsequently, the selected variables were subjected to a multifactorial logistic regression analysis to determine independent risk factors for prolonged ICU LOS in patients with DKA. A nomogram prediction model was constructed based on the identified predictors. The multivariate variables included in this nomogram prediction model were the Oxford acute severity of illness score (OASIS), Glasgow coma scale (GCS), acute kidney injury (AKI) stage, vasoactive agents, and myocardial infarction.

The prediction model had a high predictive efficacy, with an area under the curve value of 0.870 (95% confidence interval [CI], 0.831-0.908) in the training cohort and 0.858 (95% CI, 0.799-0.916) in the validation cohort. A highly accurate predictive model was depicted in both cohorts using the Hosmer-Lemeshow (H-L) test and calibration plots.

The nomogram prediction model proposed in this study has a high clinical application value for predicting prolonged ICU LOS in patients with DKA. This model can help clinicians identify patients with DKA at risk of prolonged ICU LOS, thereby enhancing prompt intervention and improving prognosis.

Describe the use of fixed-rate intravenous insulin infusions (FRIs) in cats and dogs with diabetic ketoacidosis (DKA) and determine if this is associated with faster resolution of ketosis compared to variable-rate intravenous insulin infusions (VRIs). Secondary objectives were to evaluate complication rates, length of hospitalization (LOH), and survival to discharge (STD).

Randomized clinical trial (January 2019 to July 2020).

University veterinary teaching hospital and private referral hospital.

Dogs and cats with DKA and venous pH <7.3, blood glucose concentration >11 mmol/L (198 mg/dL), and β-hydroxybutyrate (BHB) concentration >3 mmol/L were eligible for inclusion. Patients were randomly assigned to receive either FRI or VRI.

Neutral (regular) insulin was administered IV as an FRI or VRI. For FRI, the rate was maintained at 0.01 IU/kg/h. For VRI, the dose was adjusted according to blood glucose concentration.

Sixteen cats and 20 dogs were enrolled. Population characteristics, mean insulin infusion rate, time to resolution of ketosis (BHB <0.6 mmol/L), complications, LOH, and STD were evaluated. In cats, overall resolution of ketosis was low (9/16 [56.3%]), limiting comparison of protocols. In dogs, resolution of ketosis was high (19/20 dogs [95.0%]) but the time to resolution in the FRI group was not different than that in the VRI group (P = 0.89), despite a 25% higher average insulin infusion rate in the FRI group (P = 0.04). The incidence of complications was low and did not differ between protocols. In cats, LOH and STD did not differ between protocols. All cats that died (5/16) did so within 78 hours and none had resolution of ketosis. Dogs receiving FRI had a shorter LOH (P = 0.01) but STD did not differ between protocols. Six dogs (30.0%) did not survive to hospital discharge but all had resolution of ketosis.

FRIs can be used in veterinary species but may not hasten resolution of ketosis.

Diabetes mellitus (DM) is a chronic medical condition that continues to increase in prevalence. Complications of DM, including diabetic ketoacidosis and hyperglycemic hyperosmolar state, often present in the emergency department requiring emergent management. Prompt assessment, diagnosis, evaluation of laboratory values, treatment, monitoring, and strict follow-up education are essential to the successful management of this complex disease. Common medications and management strategies are key elements to control DM. This article presents an overview of DM, including its prevalence, pathophysiology, presentations, and management.

Diabetic ketoacidosis (DKA) is a common clinical problem. When patients develop severe shock and/or respiratory failure, extracorporeal membrane oxygenation (ECMO) may be considered. This case series describes the clinical presentation and outcomes of patients with DKA supported with ECMO.

We conducted a retrospective and anonymized review of 15 patients with DKA who required ECMO at our institution. Demographic and ECMO-specific data were collected. Additional variables include ICU length of stay (LOS), acute kidney injury and use of continuous renal replacement therapy, disposition, and mortality.

All ECMO cannulations were performed by an intensivist using peripheral vascular access. The majority of patients were female (73%) with a median age of 27 (IQR = 21.5-45) years. A diagnosis of diabetes mellitus (DM) prior to ECMO was present in 11 (73%) patients. Venoarterial ECMO was the initial mode used in 11 (73%) patients. The median duration of ECMO support was 7 (IQR = 6-14) days. The median ICU LOS was 12 (IQR = 8.5-20.5) days, and the median hospital LOS was 21 (IQR = 11-36.5) days. Eight patients had cardiac arrest and underwent extracorporeal cardiopulmonary resuscitation (ECPR) of which 4 (50%) patients survived to discharge. Overall, 10 (66.7%) patients were successfully weaned from ECMO and survived to discharge.

This is the largest case series regarding the use of ECMO for patients with refractory shock, cardiac arrest, or respiratory failure related to DKA. The findings suggest that ECMO is a viable support option for managing these patients and has excellent outcomes, including patients with cardiac arrest.

This article reviews the most current literature on diabetic ketoacidosis, including how to make the diagnosis and management. It discusses euglycemic diabetic ketoacidosis and the risk factors for this rare but dangerous disease process. Pertinent pearls and pitfalls encountered by the emergency physician when managing these patients are included. Because these patients often stay in the emergency department for prolonged periods, recommendations on transitioning to subcutaneous insulin are included, along with dosing recommendations. Finally, the article reviews how to disposition patients with diabetic ketoacidosis and examines important factors that lead to a successful discharge home.

Abnormalities in serum potassium are commonly encountered in patients presenting to the emergency department. A variety of acute and chronic causes can lead to life-threatening illness in both hyperkalemia and hypokalemia. Here we summarize the relevant causes, risks, and treatment options for these frequently encountered disorders.

Studies using fast-acting subcutaneous (SQ) insulin analogs in diabetic ketoacidosis (DKA) have demonstrated efficacy, safety, and cost-effectiveness, allowing treatment of mild-to-moderate (MTM)-severity DKA patients in non-intensive care unit (ICU) settings. However, emergency department (ED)-based studies are few, with limited exploration of impacts on operational metrics.

We implemented the SQuID (Subcutaneous Insulin in Diabetic Ketoacidosis) protocol for adults with MTM-severity DKA in an urban academic ED, collecting data from August 1, 2021, to February 28, 2022. We examined fidelity (frequency of required q2h glucose checks), safety (proportion of patients administered rescue dextrose for hypoglycemia), and ED length of stay (EDLOS) for the SQuID cohort compared to patients (non-ICU) treated with a traditional insulin infusion. We also examined ICU admission rate among MTM-severity DKA patients after introduction of SQuID to two historical control periods (pre-intervention and pre-COVID). We used Mann-Whitney U to test for differences in EDLOS distributions, bootstrapped (n = 1000) confidence intervals (CIs) for EDLOS median differences, and the two-sample z-test for differences in ICU admissions.

We identified 177 MTM-severity DKA patients in the study period (78 SQuID, 99 traditional cohort) and 163 preintervention and 161 pre-COVID historical control patients. Fidelity to the SQuID pathway was good, with glucose checks exceeding the q2-h requirement. We found no difference in the proportion of rescue dextrose administration compared to the traditional pathway. We observed significant reductions in median EDLOS for the SQuID cohort compared to the traditional cohort during the study period (-3.0, 95% CI -8.5 to -1.4), the preintervention period (-1.4, 95% CI -3.1 to -0.1), and the pre-COVID control period (-3.6, 95% CI -7.5 to -1.8).

In this single-center study at an academic ED, treatment of patients with MTM-severity DKA with a SQ insulin protocol was effective, demonstrated equivalent safety, and reduced ED length of stay.

Diabetes mellitus is a common endocrinopathy in dogs and cats. Diabetes ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are life-threatening complications of diabetes resulting from an imbalance between insulin and the glucose counter-regulatory hormones. The first part of this review focuses on the pathophysiology of DKA and HHS, and rarer complications such as euglycemic DKA and hyperosmolar DKA. The second part of this review focuses on the diagnosis and treatment of these complications.

Circular RNAs (circRNAs) are associated with diabetes, but their role in fulminant type 1 diabetes (FT1D) is unclear. Thus, we characterized the role of circRNAs in FT1D.

CircRNA expression profiles were detected in peripheral blood mononuclear cells (PBMCs) of five FT1D patients and five controls using a circRNA microarray. An independent cohort comprised of 40 FT1D cases, 75 type 1 diabetes (T1D) cases, and 115 controls was used to verify the circRNAs using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman's correlation analysis and receiver operating characteristic (ROC) curve analysis were performed to determine the clinical diagnostic capability of circRNAs. Bioinformatics was used to identify potential biological functions and circRNA-miRNA-mRNA interactions.

There were 13 upregulated and 13 downregulated circRNAs in PBMCs of patients with FT1D. Five circRNAs were further verified in a second cohort. Hsa_circRNA_100632 was significantly upregulated in the FT1D and T1D groups. Hsa_circRNA_100632 was differentiated between patients with FT1D and controls [area under the curve (AUC) 0.846; 95% CI 0.776-0.916; P<0.0001] as well as between patients with FT1D and patients with T1D (AUC 0.726; 95% CI 0.633-0.820; P<0.0001). Bioinformatics analysis showed that hsa_circRNA_100632 may be involved in 47 circRNA-miRNA-mRNA signaling pathways associated with diabetes.

CircRNAs were aberrantly expressed in PBMCs of patients with FT1D, and hsa_circRNA_100632 may be a diagnostic marker of FT1D.

Significance: Cancer-associated tissue-specific lactic acidosis stimulates and mediates tumor invasion and metastasis and is druggable. Rarely, malignancy causes systemic lactic acidosis, the role of which is poorly understood. Recent Advances: The understanding of the role of lactate has shifted dramatically since its discovery. Long recognized as only a waste product, lactate has become known as an alternative metabolism substrate and a secreted nutrient that is exchanged between the tumor and the microenvironment. Tissue-specific lactic acidosis is targeted to improve the host body's anticancer defense and serves as a tool that allows the targeting of anticancer compounds. Systemic lactic acidosis is associated with poor survival. In patients with solid cancer, systemic lactic acidosis is associated with an extremely poor prognosis, as revealed by the analysis of 57 published cases in this study. Although it is considered a pathology worth treating, targeting systemic lactic acidosis in patients with solid cancer is usually inefficient. Critical Issues: Research gaps include simple questions, such as the unknown nuclear pH of the cancer cells and its effects on chemotherapy outcomes, pH sensitivity of glycosylation in cancer cells, in vivo mechanisms of response to acidosis in the absence of lactate, and overinterpretation of in vitro results that were obtained by using cells that were not preadapted to acidic environments. Future Directions: Numerous metabolism-targeting anticancer compounds induce lactatemia, lactic acidosis, or other types of acidosis. Their potential to induce acidic environments is largely overlooked, although the acidosis might contribute to a substantial portion of the observed clinical effects. Antioxid. Redox Signal. 37, 1130-1152.

In this review, the authors discuss potential clinical applications for continuous ketone monitoring (CKM) in a broad continuum of clinical settings from pre-hospital care and the emergency department to acute inpatient management and post-discharge follow-up.

Though in its early stages, the concept of a novel continuous ketone sensing technology exerts great potential for use in the detection and hospital management of DKA, namely to overcome diagnostic barriers associated with ketoacidosis in patients with diabetes and obtain real-time BOHB levels, which may be useful in understanding both patients' response to treatment and DKA trajectory. Peri- and intra-operative use of CKM technology can potentially be applied in a number of urgent and elective surgical procedures frequently underwent by patients with diabetes and in the observation of patients during peri-operative fasting. In transitional care management, CKM technology could potentially facilitate patients' safe transition through levels of care, following hospital discharge from a DKA episode. This evaluation of the literature presents the potential advantages of adopting CKM and integrating this technology into the care algorithm of patients at risk for ketoacidosis.

Current guidelines suggest the use of isotonic saline (IS) infusion as the preferred resuscitation fluid in the management of diabetic ketoacidosis (DKA). However, balanced electrolyte solutions (BES) have been proposed as an alternative due to a lower propensity to cause hyperchloremic metabolic acidosis. Evidence regarding the use of BES in DKA remains limited.

To determine if the use of BES in fluid resuscitation leads to faster resolution of DKA compared to IS.

The study involves a comprehensive search of literature from PubMed, Cochrane CENTRAL, Google Scholar, and Science Direct of clinical trials addressing the use of BES vs IS in fluid resuscitation in DKA. The time to resolution of DKA was examined as the primary endpoint. Pooled hazard ratios (HR) and Mean Difference (MD) in hours with their 95% confidence intervals (CI) were calculated using a random-effects model.

The literature search included 464 studies that were screened individually. A total of 9 studies were identified but 6 studies were excluded due to irrelevance in the outcome of interest and target population. The pooled hazard ratio HR significantly revealed 1.46 [1.10 to 1.94] (p = 0.009) with 12% heterogeneity while MD was -3.02 (95% CI -6.78-0.74; p = 0.12) with heterogeneity of 85%.

Considering the evidence from pooled small randomized trials with moderate overall certainty of evidence, the use of BES in DKA was associated with faster rates of DKA resolution compared to IS.

Diabetic ketoacidosis (DKA) patients present with low serum bicarbonate ( HCO3-${\rm{HCO}}_{3}^{-} $ ), and an increase in its level to ≥15 mEq/L is considered one of the criteria for DKA resolution. Both proton pump inhibitors and histamine-2 receptor antagonists inhibit downstream functioning of H⁺ /K⁺ ATPase in the gastric parietal cells, which results in the decreased secretion of HCO3-${\rm{HCO}}_{3}^{-} $ into the bloodstream.

We aimed to introduce the hypothesis that DKA patients on acid-suppressive medications may have a delayed rise in serum HCO3-${\rm{HCO}}_{3}^{-} $ to >15 mEq/L that may cause increased hospital length of stay (LOS) and sought to compare the outcomes of such patients. For the sake of simplicity, conditions requiring acid suppression are grouped under the term peptic ulcer disease (PUD) in this study.

This is a retrospective study using Nationwide Inpatient Sample employing International Classification of Diseases (ICD-10) codes for adult patients with a primary diagnosis of DKA. Analyses were performed using STATA, proportions were compared using Fisher exact test, and continuous variables using Student's t-test. Confounding variables were adjusted using propensity matching, multivariate logistic, and linear regression analyses.

DKA patients with PUD had higher adjusted LOS, intensive care unit admission, and total hospital costs. Mortality and morbidity indicators were similar in both groups. The variables found to be independent predictors of increased LOS were malnutrition, Clostridium difficile infection, pneumonia, Glasgow Coma Scale score of 3-8, and higher Charlson comorbidity score.

We found that Clostridium difficile and pneumonia predicted longer LOS in DKA patients with concomitant PUD, hinting at the possible role of acid suppression in prolonging the LOS in such patients. However, further studies are needed to examine the effect of lesser HCO3-${\rm{HCO}}_{3}^{-} $ generation on LOS.

Diabetic ketoacidosis and hyperosmolar hyperglycemic state are life-threatening hyperglycemic crises often requiring intensive care unit (ICU) management. Treatment includes intravenous (IV) insulin with a transition to subcutaneous (SC) insulin upon resolution. Hypoglycemia is a common complication associated with treatment of hyperglycemic crises, but risk factors have not been well established. This study aimed to assess risk factors associated with hypoglycemia during treatment for hyperglycemic crises.

This case-control study included ICU patients admitted with hyperglycemic crises at a single Veterans Affairs health system from 1 January 2013 to 31 March 2020. Patients who developed hypoglycemia during insulin treatment were compared with a control group. Odds of hypoglycemia were assessed based on risk factors, including BMI, comorbidities, and type of SC insulin used.

Of the 216 cases of hyperglycemic crises included, hypoglycemia occurred in 61 cases (44 on SC insulin, 11 on IV insulin, and 6 on both). Odds for hypoglycemia were significantly higher for underweight patients (odds ratio 4.52 [95% CI 1.05-19.55]), type 1 diabetes (4.02 [2.09-7.73]), chronic kidney disease (1.94 [1.05-3.57]), those resumed on the exact chronic SC insulin regimen following resolution (2.91 [1.06-7.95]), and patients who received NPH versus glargine insulin (5.13 [1.54-17.06]). No significant differences were seen in the other evaluated variables.

This study found several factors associated with hypoglycemia during hyperglycemic crises treatment, many of which are not addressed in consensus statement recommendations. These findings may help ICU clinicians prevent complications related to hyperglycemic crisis management and generate hypotheses for future studies.

To assess the risk of new-onset type 1 diabetes mellitus (T1D) diagnosis following COVID-19 diagnosis and the impact of COVID-19 diagnosis on the risk of diabetic ketoacidosis (DKA) in patients with prior T1D diagnosis.

Retrospective data consisting of 27,292,879 patients from the Cerner Real-World Data were used. Odds ratios, overall and stratified by demographic predictors, were calculated to assess associations between COVID-19 and T1D. Odds ratios from multivariable logistic regression models, adjusted for demographic and clinical predictors, were calculated to assess adjusted associations between COVID-19 and DKA. Multiple imputation with multivariate imputation by chained equations (MICE) was used to account for missing data.

The odds of developing new-onset T1D significantly increased in patients with COVID-19 diagnosis (OR: 1.42, 95% CI: 1.38, 1.46) compared to those without COVID-19. Risk varied by demographic groups, with the largest risk among pediatric patients ages 0-1 years (OR: 6.84, 95% CI: 2.75, 17.02) American Indian/Alaskan Natives (OR: 2.30, 95% CI: 1.86, 2.82), Asian or Pacific Islanders (OR: 2.01, 95% CI: 1.61, 2.53), older adult patients ages 51-65 years (OR: 1.77, 95% CI: 1.66, 1.88), those living in the Northeast (OR: 1.71, 95% CI: 1.61, 1.81), those living in the West (OR: 1.65, 95% CI: 1.56, 1.74), and Black patients (OR: 1.59, 95% CI: 1.47, 1.71). Among patients with diagnosed T1D at baseline (n = 55,359), 26.7% (n = 14,759) were diagnosed with COVID-19 over the study period. The odds of developing DKA for those with COVID-19 were significantly higher (OR 2.26, 95% CI: 2.04, 2.50) than those without COVID-19, and the largest risk was among patients with higher Elixhauser Comorbidity Index.

COVID-19 diagnosis is associated with significantly increased risk of new-onset T1D, and American Indian/Alaskan Native, Asian/Pacific Islander, and Black populations are disproportionately at risk. In patients with pre-existing T1D, the risk of developing DKA is significantly increased following COVID-19 diagnosis.

Evaluating the impact of Ramadan fasting on Ambulatory Glucose Profile (AGP) among Patients with Type 1 Diabetes (T1D) using Flash Glucose Monitoring (FGM) System.

The present study is a comparative study, performed using 87 patients with T1D, whose health status permitted them to fast, based on the risk stratification adopted by Diabetes and Ramadan (DAR Guidelines). Besides the demographic data, other data connected with the glycemic profile such as the mean Time in Range (TIR), mean Time Above Range (TAR), mean Time Below Range (TBR), mean glucose level, hemoglobin A1c (HbA1c), Glucose Variability (GV), and Glucose Monitoring Indicator (GMI %), were recorded at three specific periods, namely, pre- (prior to), during and post Ramadan.

The mean age of the study population was 21.3 ± 8.2 years, and 52.9% of this population was female. Compared to the pre-Ramadan data, no significant alterations (p > 0.05) were noted in terms of the low glucose events, percentage of glucose level below 70 mg/dL, the average duration of hypoglycemic events, and percentage of glucose level below 54 mg/dL, from the values observed during and post-Ramadan. In comparison with the pre-Ramadan data, no significant changes appeared (p > 0.05) concerning the GV, average glucose, GMI, percentage within target, TAR (181-250 mg/dL), and percentage >250 mg/dL), for the periods during and post-Ramadan, except scanning of FreeStyle Libre (p = 0.042) during Ramadan month compared to pre-Ramadan.

Fasting during Ramadan was achievable in patients with T1D who received adequate counseling and support.

Standard diabetic ketoacidosis care in the US includes intravenous insulin treatment in the intensive care unit. Subcutaneous (SQ) insulin could decrease intensive care unit need, but the data are limited.

To assess outcomes after implementation of an SQ insulin protocol for treating diabetic ketoacidosis.

This cohort study is a retrospective evaluation of a prospectively implemented SQ insulin protocol. The study was conducted at an integrated health care system in Northern California. Participants included hospitalized patients with diabetic ketoacidosis at 21 hospitals between January 1, 2010, and December 31, 2019. The preimplementation phase was 2010 to 2015, and the postimplementation phase was 2017 to 2019. Data analysis was performed from October 2020 to January 2022.

An SQ insulin treatment protocol for diabetic ketoacidosis.

Difference-in-differences evaluation of the need for intensive care, mortality, readmission, and length of stay at a single intervention site using an SQ insulin protocol from 2017 onward compared with 20 control hospitals using standard care.

A total of 7989 hospitalizations for diabetic ketoacidosis occurred, with 4739 (59.3%) occurring before and 3250 (40.7%) occurring after implementation. The overall mean (SD) age was 42.3 (17.7) years, with 4137 hospitalizations (51.8%) occurring among female patients. Before implementation, SQ insulin was the first insulin used in 40 intervention (13.4%) and 651 control (14.7%) hospitalizations. After implementation, 98 hospitalizations (80.3%) received SQ insulin first at the intervention site compared with 402 hospitalizations (12.8%) at control sites. The adjusted rate ratio for intensive care unit admission was 0.43 (95% CI, 0.33-0.56) at the intervention sites, a 57% reduction compared with control sites, and was 0.50 (95% CI, 0.25-0.99) for 30-day hospital readmission, a 50% reduction. There were no significant changes in hospital length of stay and rates of death.

These findings suggest that a protocol based on SQ insulin for diabetic ketoacidosis treatment was associated with significant decreases in intensive care unit need and readmission, with no evidence of increases in adverse events.

Diabetes mellitus (DM) is among the chronic metabolic disorders that its incidence rate has shown an increase in developed and wealthy countries due to lifestyle and obesity. The treatment of DM has always been of interest, and significant effort has been made in this field. Exosomes belong to extracellular vesicles with nanosized features (30-150 nm) that are involved in cell-to-cell communication and preserving homeostasis. The function of exosomes is different based on their cargo, and they may contain lipids, proteins, and nucleic acids. The present review focuses on the application of exosomes in the treatment of DM; both glucose and lipid levels are significantly affected by exosomes, and these nanostructures enhance lipid metabolism and decrease its deposition. Furthermore, exosomes promote glucose metabolism and affect the level of glycolytic enzymes and glucose transporters in DM. Type I DM results from the destruction of β cells in the pancreas, and exosomes can be employed to ameliorate apoptosis and endoplasmic reticulum (ER) stress in these cells. The exosomes have dual functions in mediating insulin resistance/sensitivity, and M1 macrophage-derived exosomes inhibit insulin secretion. The exosomes may contain miRNAs, and by transferring among cells, they can regulate various molecular pathways such as AMPK, PI3K/Akt, and β-catenin to affect DM progression. Noteworthy, exosomes are present in different body fluids such as blood circulation, and they can be employed as biomarkers for the diagnosis of diabetic patients. Future studies should focus on engineering exosomes derived from sources such as mesenchymal stem cells to treat DM as a novel strategy.

Fulminant type 1 diabetes (FT1D) could present diabetes ketoacidosis (DKA) at early onset. It is crucial to identify FT1D from DKA manifestations in time at clinical practice. This study was aimed at investigating whether the fulminant index (FI), encompassing plasma glucose (PG) to glycated haemoglobin (HbA1c) ratio (PG/HbA1c), serum potassium ion (K⁺ ) to HbA1c ratio (K⁺ /HbA1c) and serum sodium ion (Na⁺ ) multiplied by HbA1c (Na⁺ *HbA1c), is a feasible indicator for early FT1D diagnosis.

A total of 78 subjects were enroled, including 40 FT1D patients and 38 non-FT1D patients with DKA. We utilised receiver operating characteristic (ROC) curve analysis to determine the FI cut-off values between FT1D and non-FT1D groups and examined efficacies of FI based on statistics.

ROC curve analyses showed that the maximum Youden's index for PG/HbA1c bonding to a cut-off value of 4.389, with the sensitivity of 75.0% and specificity of 81.6% in identifying FT1D from DKA. And optimal K⁺ /HbA1c cut-off value was 0.728 with a sensitivity of 90.0% and specificity of 84.2%. For Na⁺ *HbA1c, the best cut-off value was 923.65, and its sensitivity and specificity were 85% and 73.7%, respectively.

These results suggested FI could work as a valid and convenient indicator for differentiating FT1D from initial DKA patients. FI (K⁺ /HbA1c) presented the best efficacy as an independent index.

The novel coronavirus disease 2019 (COVID-19) has heterogenous clinical courses, indicating that there might be distinct subphenotypes in critically ill patients. Although prior research has identified these subphenotypes, the temporal pattern of multiple clinical features has not been considered in cluster models. We aimed to identify temporal subphenotypes in critically ill patients with COVID-19 using a novel sequence cluster analysis and associate them with clinically relevant outcomes.

We analyzed 1036 confirmed critically ill patients with laboratory-confirmed SARS-COV-2 infection admitted to the Mount Sinai Health System in New York city. The agglomerative hierarchical clustering method was used with Levenshtein distance and Ward's minimum variance linkage.

We identified four subphenotypes. Subphenotype I (N = 233 [22.5%]) included patients with rapid respirations and a rapid heartbeat but less need for invasive interventions within the first 24 hours, along with a relatively good prognosis. Subphenotype II (N = 418 [40.3%]) represented patients with the least degree of ailments, relatively low mortality, and the highest probability of discharge from the hospital. Subphenotype III (N = 259 [25.0%]) represented patients who experienced clinical deterioration during the first 24 hours of intensive care unit admission, leading to poor outcomes. Subphenotype IV (N = 126 [12.2%]) represented an acute respiratory distress syndrome trajectory with an almost universal need for mechanical ventilation.

We utilized the sequence cluster analysis to identify clinical subphenotypes in critically ill COVID-19 patients who had distinct temporal patterns and different clinical outcomes. This study points toward the utility of including temporal information in subphenotyping approaches.

This study aimed to investigate the relationship between 25-hydroxyvitamin D (25OHD) and the onset of ketosis in newly diagnosed patients with ketosis-prone type 2 diabetes (KPT2D).

A total of 162 patients with non-autoimmune newly diagnosed diabetes mellitus were included in this cross-sectional study. Patients were classified into KPT2D (n = 71) or non-ketotic type 2 diabetes (NKT2D, n = 91). Anthropometric parameters, islet functions, biochemical parameters, and body composition were determined in both KPT2D and NKT2D groups. Correlation analysis was performed to determine the associations between 25OHD and plasma ketones. The risk factors associated with ketosis episodes in patients with new-onset KPT2D were evaluated using binary logistic regression analysis.

Vitamin D deficiency was observed in both patients with KPT2D and NKT2D. Compared with the NKT2D group, serum 25OHD values were lower in the participants of the KPT2D group [14.20 (10.68, 19.52) vs 16.98 (13.54,2.96) ng/mL, P = 0.011]. Serum 25OHD was associated with plasma ketones (R = -0.387). Serum 25OHD is an independent protective factor for ketosis or ketoacidosis episodes in patients with new onset of KPT2D (P = 0.037, OR = 0.921).

Vitamin D levels are associated with ketosis episodes in patients with KPT2D. Serum 25OHD is an independent protective factor for ketosis episodes in patients with KPT2D.

Ketone bodies have been identified as an important, alternative fuel source in heart failure. In addition, the use of ketone bodies as a fuel source has been suggested to be a potential ergogenic aid for endurance exercise performance. These findings have certainly renewed interest in the use of ketogenic diets and exogenous supplementation in an effort to improve overall health and disease. However, given the prevalence of ischemic heart disease and myocardial infarctions, these strategies may not be ideal for individuals with coronary artery disease. Although research studies have clearly defined changes in fatty acid and glucose metabolism during ischemia and reperfusion, the role of ketone body metabolism in the ischemic and reperfused myocardium is less clear. This review will provide an overview of ketone body metabolism, including the induction of ketosis via physiological or nutritional strategies. In addition, the contribution of ketone body metabolism in healthy and diseased states, with a particular emphasis on ischemia-reperfusion (I-R) injury will be discussed.

The HCO3- concentration in venous serum ([HCO3-]s) is a factor commonly used for detecting the body pH and metabolic conditions. To exactly detect [HCO3-]s, the venous CO2 pressure should be kept as it is in the vein. The [HCO3-]s measurement is technically complicated to apply for huge numbers of almost heathy persons taking only basic medical examinations. The summation of [HCO3-]s and the venous serum Cl- concentration ([Cl-]s) is approximately constant; therefore, we studied if [Cl-]s could be a marker detecting metabolic conditions instead of [HCO3-]s. Venous blood was obtained from persons taking basic medical examinations (the number of persons = 107,630). Older persons showed higher values of [Cl-]s, fasting blood sugar (FBS), and glycated hemoglobin (HbA1c) than younger ones. [Cl-]s showed positive correlation to age and negative correlation to FBS and HBA1c. The negative correlation of [Cl-]s to FBS/HbA1c was obvious in persons with high FBS/HbA1c, leading us to an idea that persons with high FBS/HbA1c show high [HCO3-]s, which might be caused by low activity of carbonic anhydrase in the lung observed in persons with diabetes mellitus under acidotic conditions. Taken together, an easily measured serum electrolyte, [Cl-]s, could be a useful marker estimating metabolic conditions.