Peri-colonoscopy Implications of Sodium-Glucose Cotransporter-2 Inhibitor Therapy: A Mini-review of Available Evidence.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a class of oral glucose-lowering agents commonly used for the treatment of type 2 diabetes. With increased use, there has been an increase in the incidence of the rare but life-threatening complication of euglycemic diabetic ketoacidosis. A common but underappreciated precipitant is colonoscopy. In this work, we outline the pathophysiology of the interaction between colonoscopy and SGLT2i use, the evidence regarding SGLT2i use in the periprocedural setting and Australian Diabetes Society guidelines.

Successful therapeutic plasma exchange in a case with extremely severe hypertriglyceridemia secondary to diabetic ketoacidosis concomitant with type IX glycogen storage disease.

Herein, we aimed to present a child with extremely severe hypertriglyceridemia (ESHTG) secondary to diabetic ketoacidosis concomitant with type IX glycogen storage disease (GSD). Extremely severe hypertriglyceridemia (10 700 mg/dL) was detected through the apparent lipemic appearance of the sampled blood in a 17-year-old male patient with severe diabetic ketoacidosis. In spite of insulin infusion, the patient's clinical condition deteriorated to acute pancreatitis. Single sessions of therapeutic plasma exchange (TPE) along with insulin treatment have successfully intercepted the progression of the state of acute pancreatitis. The patient was also diagnosed with type IX GSD on the basis of the genetic analyses performed for the potential underlying metabolic diseases. In conclusion, underlying metabolic diseases, such as glycogen storage disease, should be investigated in patients with diabetic ketoacidosis accompanied by severe hypertriglyceridemia. If ESHTG does not relieve despite insulin infusion, and/or acute pancreatitis occurs as a complication, TPE should be kept in mind.

Tubular injury in diabetic ketoacidosis: Results from the diabetic kidney alarm study.

OBJECTIVE: Glomerular injury is a recognized complication of diabetic ketoacidosis (DKA), yet the tubular lesions are poorly understood. The aim of this prospective study was to evaluate the presence and reversibility of tubular injury during DKA in children with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Blood and urine samples were collected from 40 children with DKA (52% boys, mean age 11 ± 4 years, venous pH 7.2 ± 0.1, glucose 451 ± 163 mg/dL) at three timepoints: 0-8 and 12-24 h after starting insulin, and 3 months after discharge. Mixed-effects models evaluated the changes in tubular injury markers over time (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1 [KIM-1], and interleukin 18 [IL-18]). We also evaluated the relationships among the tubular injury biomarkers, copeptin, a vasopressin surrogate, and serum uric acid (SUA). RESULTS: Serum NGAL, KIM-1, and IL-18 were highest at 0-8 h (306.5 ± 45.9 ng/mL, 128.9 ± 10.1 pg/mL, and 564.3 ± 39.2 pg/mL, respectively) and significantly decreased over 3 months (p = 0.03, p = 0.01, and p < 0.001, respectively). There were strong relationships among increases in copeptin and SUA and rises in tubular injury biomarkers. At 0-8 h, participants with acute kidney injury (AKI) [17%] showed significantly higher concentrations of tubular injury markers, copeptin, and SUA. CONCLUSIONS: DKA was characterized by tubular injury, and the degree of injury associated with elevated copeptin and SUA. Tubular injury biomarkers, copeptin and SUA may be able to predict AKI in DKA.

Awareness of euglycaemic diabetic ketoacidosis during pregnancy prevents recurrence of devastating outcomes: a case report of two pregnancies in one patient.

BACKGROUND: Euglycaemic diabetic ketoacidosis (DKA) during pregnancy is a life-threatening obstetric emergency. It requires early identification and prompt action. Obstetricians' knowledge about symptoms, diagnostic pitfalls and management during pregnancy and delivery need to be improved. We report a case of a young diabetic woman developing severe euglycaemic DKA in two consecutive pregnancies; the first pregnancy resulted in the most deviating outcome (i.e., intrauterine death), while the second pregnancy resulted in the delivery of a healthy newborn. Thus, the novelty of the case presented here is the possibility to demonstrate how the management of DKA in pregnancy can dramatically change outcomes. CASE PRESENTATION: We report a case of a young diabetic woman in whom DKA was concealed by hyperemesis and oesophageal reflux. This woman presented to our delivery unit with severe euglycaemic DKA during her first pregnancy. While the mother's condition could be successfully stabilized, the foetus died shortly after admission. Two years later, the same woman presented with similar problems. Repeated episodes of mild euglycaemic DKA could be successfully managed with consequent interdisciplinary treatment and close observation, leading to a good pregnancy outcome, i.e., the birth of a healthy child. CONCLUSION: Awareness of euglycaemic DKA needs to be increased to reduce the risk of severe complications during pregnancies in diabetic women. This case report demonstrates that increased awareness of DKA with immediate recognition and a successful multidisciplinary approach are mandatory for an positive pregnancy outcomes.

The Impact of Hypo- and Hyperglycemia on Cognition and Brain Development in Young Children with Type 1 Diabetes.

Human and experimental animal data suggest both hyperglycemia and hypoglycemia can lead to altered brain structure and neurocognitive function in type 1 diabetes (T1D). Young children with T1D are prone to extreme fluctuations in glucose levels. The overlap of these potential dysglycemic insults to the brain during the time of most active brain and cognitive development may cause cellular and structural injuries that appear to persist into adult life. Brain structure and cognition in persons with T1D are influenced by age of onset, exposure to glycemic extremes such as severe hypoglycemic episodes, history of diabetic ketoacidosis, persistent hyperglycemia, and glucose variability. Studies using brain imaging techniques have shown brain changes that appear to be influenced by metabolic abnormalities characteristic of diabetes, changes apparent at diagnosis and persistent throughout adulthood. Some evidence suggests that brain injury might also directly contribute to psychological and mental health outcomes. Neurocognitive deficits manifest across multiple cognitive domains. Moreover, impaired executive function and mental health can affect patients' adherence to treatment. This review summarizes the current data on the impact of glycemic extremes on brain structure and cognitive function in youth with T1D and the use of new diabetes technologies that may reduce these complications.

A rare case of diabetic ketoacidosis presenting with severe hypertriglyceridemia requiring plasmapheresis in an adult with type-2 diabetes mellitus: Case report.

INTRODUCTION: Severe hypertriglyceridemia (HTG) is a rare complication of insulin resistance. Its presentation with diabetic ketoacidosis (DKA) has been reported in a few cases, where most patients have type-1 diabetes mellitus (DM). Our case represents a unique presentation of DKA associated with severe HTG above 10,000 mg/dL in an adult with type-2 DM. PATIENT CONCERNS AND DIAGNOSIS: Case Report: A 51-year-old man with no prior illnesses presented to the emergency department with abdominal pain and nausea. He was found to have DKA with a blood glucose level of 337 mg/dL, pH of 7.17, beta-hydroxybutyrate of 7.93 mmol/L, and anion gap of 20 mmol/L. His triglyceride levels were >10,000 mg/dL. His serum was found to be lipemic. Computerized tomography scan of the abdomen demonstrated mild acute pancreatitis. Negative GAD65 antibodies supported the diagnosis of type-2 DM. INTERVENTIONS AND OUTCOMES: Endocrinology was consulted and one cycle of albumin-bound plasmapheresis was administered. This therapy significantly improved his HTG. DKA gradually resolved with insulin therapy as well. He was discharged home with endocrinology follow-up. CONCLUSION: This unique case highlights an uncommon but critical consequence of uncontrolled DM. It brings forth the possibility of severe HTG presenting as a complication of uncontrolled type-2 DM. Severe HTG commonly presents with acute pancreatitis, which can be debilitating if not managed promptly. Most patients with this presentation are managed with insulin infusion. The use of plasmapheresis for management of severe HTG has not been well studied. Our case supports the use of plasmapheresis as an effective and rapid treatment for severe HTG.

The Heart in Diabetic Ketoacidosis: A Narrative Review Focusing on the Acute Cardiac Effects and Electrocardiographic Abnormalities.

Diabetic ketoacidosis (DKA) is a serious complication of diabetes mellitus. Hyperglycemia, acidosis, and electrolyte imbalances can directly affect the heart by inducing toxicity, impairing myocardial blood flow, autonomic dysfunction, and altering activation and conduction of electrical impulses throughout the heart, increasing the risk of arrhythmias and ischemia. The electrocardiogram is useful in monitoring patients during and after an episode of DKA, as it allows the detection of arrhythmias and guides metabolic correction. Unfortunately, reports on electrocardiographic abnormalities in patients with DKA are lacking. We found two electrocardiographic patterns that are frequently reported in the literature: a pseudo-myocardial infarction and a Brugada Phenocopy. Both are associated with DKA metabolic anomalies and they resolve after treatment. Because of their clinical relevance and the challenge they represent for clinicians, we analyzed the clinical characteristics of these patients and the mechanisms involved in these electrocardiographic findings.

Biochemical Parameters of Diabetes Ketoacidosis in Patients with End-stage Kidney Disease and Preserved Renal Function.

INTRODUCTION: Differences in biochemical parameters of diabetic ketoacidosis in patients with end-stage kidney disease (ESKD) has not been established. Accordingly, we assessed the relationship between degree of metabolic acidosis and ß-hydroxybutyrate in patients with ESKD (eGFR < 15 mL/min/1.73 m2), moderate renal failure (eGFR 15-60), or preserved renal function (eGFR > 60). METHODS: This observational study included adults (18-80 years) with diabetes ketoacidosis (DKA), admitted to Emory University Hospitals between January 1, 2006 to December 31, 2016. DKA and renal stages were confirmed on admission laboratory values. RESULTS: Admission bicarbonate levels (13.9 ± 5 vs 13.4 ± 5.3 vs 13.8 ± 4.2 mmol/L, P = 0.7), and pH levels (7.2 ± 0.3 vs 7.2 ± 0.2 vs 7.2 ± 0.2, P = 0.8) were similar among groups. Patients with ESKD had lower mean ß-hydroxybutyrate level (4.3 ± 3.3 vs 5.6 ± 2.9 vs 5.9 ± 2.5 mmol/L, P = 0.01), but higher admission glucose (852 ± 340.4 vs 714.6 ± 253.3 mg/dL vs 518 ± 185.7 mg/dL, P < 0.01), anion gap (23.4 ± 7.6 vs 23 ± 6.9 vs 19.5 ± 4.7 mmol/L, P < 0.01), and osmolality (306 ± 20.6 vs 303.5 ± vs 293.1 ± 3.1mOsm/kg, P < 0.01) compared with patients with moderate renal failure and preserved renal function, respectively. The sensitivity of ß-hydroxybutyrate > 3 mmol/L for diagnosing DKA by bicarbonate level < 15 and <18 mmol/L was 86.9% and 72% in ESKD, 89.3% and 83.7% in moderate renal failure, and 96.2% and 88.3% in preserved renal function. In patients with ESKD, the corresponding ß-hydroxybutyrate with bicarbonate levels < 10, 10-15, <18 mmol/L were 5.5, 3.9, 3.0 mmol/L, respectively. CONCLUSIONS: Significant metabolic differences were found among DKA patients with different levels of renal function. In patients with ESKD, a ß-hydroxybutyrate level > 3 mmol/L may assist with confirmation of DKA diagnosis.

Acute Kidney Injury and Renal Tubular Damage in Children With Type 1 Diabetes Mellitus Onset.

CONTEXT: Acute kidney injury (AKI) and renal tubular damage (RTD), especially if complicated by acute tubular necrosis (ATN), could increase the risk of later chronic kidney disease. No prospective studies on AKI and RTD in children with type1diabetes mellitus (T1DM) onset are available. OBJECTIVES: To evaluate the AKI and RTD prevalence and their rate and timing of recovery in children with T1DM onset. DESIGN: Prospective study. SETTINGS AND PATIENTS: 185 children were followed up after 14 days from T1DM onset. The patients who did not recover from AKI/RTD were followed-up 30 and 60 days later. MAIN OUTCOME MEASURES: AKI was defined according to the KDIGO criteria. RTD was defined by abnormal urinary beta-2-microglobulin and/or neutrophil gelatinase-associated lipocalin and/or tubular reabsorption of phosphate < 85% and/or fractional excretion of Na (FENa) > 2%. ATN was defined by RTD+AKI, prerenal (P)-AKI by AKI+FENa < 1%, and acute tubular damage (ATD) by RTD without AKI. RESULTS: Prevalence of diabetic ketoacidosis (DKA) and AKI were 51.4% and 43.8%, respectively. Prevalence of AKI in T1DM patients with and without DKA was 65.2% and 21.1%, respectively; 33.3% reached AKI stage 2, and 66.7% of patients reached AKI stage 1. RTD was evident in 136/185 (73.5%) patients (32.4% showed ATN; 11.4%, P-AKI; 29.7%, ATD). All patients with DKA or AKI presented with RTD. The physiological and biochemical parameters of AKI and RTD were normal again in all patients. The former within 14 days and the latter within 2months. CONCLUSIONS: Most patients with T1DM onset may develop AKI and/or RTD, especially if presenting with DKA. Over time the physiological and biochemical parameters of AKI/RTD normalize in all patients.

Brain injury in children with diabetic ketoacidosis: Review of the literature and a proposed pathophysiologic pathway for the development of cerebral edema.

Cerebral edema (CE) is a potentially devastating complication of diabetic ketoacidosis (DKA) that almost exclusively occurs in children. Since its first description in 1936, numerous risk factors have been identified; however, there continues to be uncertainty concerning the mechanisms that lead to its development. Currently, the most widely accepted hypothesis posits that CE occurs as a result of ischemia-reperfusion injury, with inflammation and impaired cerebrovascular autoregulation contributing to its pathogenesis. The role of specific aspects of DKA treatment in the development of CE continues to be controversial. This review critically examines the literature on the pathophysiology of CE and attempts to categorize the findings by types of brain injury that contribute to its development: cytotoxic, vasogenic, and osmotic. Utilizing this scheme, we propose a multifactorial pathway for the development of CE in patients with DKA.

The case of a 69-year-old man with COVID-19 and encephalopathy.

A 69-year-old man with uncontrolled type 2 diabetes presented to an outside hospital with altered mental status. He progressed from being argumentative to encephalopathic and agitated by the evening with urinary frequency, urinary urgency, nausea, and vomiting. His vital signs were normal, and he had no focal neurological deficits on presentation. He was generally encephalopathic, only groaning with no ability to follow commands. He was found to have diabetic ketoacidosis on initial labs. A left parietal hypodensity on CT Head was found, and he was positive for Sars-COV-2.

QTc Prolongation in Pediatric Patients with Diabetic Ketoacidosis.

OBJECTIVE: To investigate the association between diabetic ketoacidosis (DKA) and prolonged QTc interval and to assess for correlation between DKA severity and QTc prolongation. STUDY DESIGN: Retrospective observational study in a pediatric hospital. Patients admitted with DKA diagnosed by laboratory criteria and an electrocardiogram (ECG) performed during a period of acidosis were identified using Looking Glass Clinical Analytics. Data including age, sex, pH, electrolytes, anion gap, and ECG variables were collected. Patients were excluded if they had a prior diagnosis of prolonged QTc or were taking QTc prolonging medications. Severity of DKA was classified as mild (pH 7.24-7.3), moderate (pH 7-7.24), or severe (pH <7). ECGs were read by a pediatric electrophysiologist and QTc interval was manually calculated utilizing the Bazett formula. RESULTS: Ninety-six patients were included (mean age 15.2 ± 4.2 years, pH 7.12 ± 0.12, bicarbonate 8.6 ± 3.7 mmol/L, potassium 5.3 ± 1.1 mEq/L). Mean QTc interval for all patients in DKA was 454 ± 32 msec. Mean QTc in the mild group was 441 ± 22 msec, moderate group 460 ± 36 msec, and severe group 461 ± 34 msec. There was a significant difference in QTc interval across DKA severity groups (P = .05). There was a significant association between higher anion gaps and greater QTc intervals (r = 0.21, P = .04). CONCLUSIONS: Thirty-one percent of pediatric patients with DKA demonstrated QTc prolongation on ECG. Severity of DKA and worsening acidosis were associated with increased prolongation of the QTc. Further study is required to evaluate the clinical impact of these findings.

Prolonged euglycemic diabetic ketoacidosis triggered by a single dose of sodium-glucose cotransporter 2 inhibitor.

A 45-year-old woman was admitted for diabetic ketoacidosis (DKA). Aggressive rehydration and continuous intravenous insulin resulted in improved blood glucose levels; however, metabolic acidosis persisted. One day prior to admission, the patient took a single dose of a sodium-glucose cotransporter 2 (SGLT2) inhibitor and this likely contributed to the prolonged euglycemic DKA. A single dose of this drug remained effective for over 100 hours as evidenced by massive excretion of urine glucose continuing long after blood glucose normalisation. SGLT2 inhibitor use should be refrained in cases in which DKA has already occurred as they may result in increasing severity or prolonged DKA.

Determinants of deranged thyroid function parameters in children admitted for management of diabetic ketoacidosis/diabetic ketosis.

BACKGROUND: Euthyroid sick syndrome (ESS) frequently arises in children admitted with diabetic ketoacidosis/diabetic ketosis (DKA/DK). This study evaluates the interplay of various metabolic factors with occurrence of deranged thyroid function tests in children suffering from DKA/DK. METHODS: 98 DKA and 96 DK pediatric patients were selected from hospital records. Those on thyroxine replacement, with overt hypothyroidism, or with positive anti-thyroperoxidase (TPO) antibody were excluded. Tests for liver function, renal function, lipid profile, serum osmolarity, thyroid function, c-peptide levels, and glycosylated hemoglobin were done on all patients. Children were divided into euthyroid (n = 88) and ESS groups (n = 106). RESULTS: The ESS group had a higher level of white blood cell count (WBC), plasma glucose (PG), beta-hydroxybutyric acid (ß-HB), triglyceride (TG), anion gap (AG), glycosylated hemoglobin (HbA1c) and a lower level of HCO3-, prealbumin (PA), and albumin (ALB) compared with the euthyroid group (P < 0.05). Free T3 (FT3) levels were significantly correlated to ß-HB, HCO3-, AG, PA, and HbA1c (r = - 0.642, 0.681, - 0.377, 0.581, - 0.309, respectively; P < 0.01). Free T4 (FT4) levels were significantly correlated to ß-HB, HCO3-, and ALB levels (r = - 0.489, 0.338, 0.529, respectively; P < 0.01). TSH levels were significantly affected by HCO3- only (r = - 0.28; P < 0.01). HCO3- level was the most important factor deciding euthyroid or ESS on logistic regression analysis (OR = 0.844, P = 0.004, 95%CI = 0.751-0.948). CONCLUSIONS: Lower levels of free thyroid hormones and occurrence of ESS were associated with a higher degree of acidosis in children with DKA/DK.

Euglycaemic diabetic ketoacidosis in a 43-year-old woman with type 2 diabetes mellitus on SGLT-2 inhibitor (empagliflozin).

We report a case of euglycaemic diabetic ketoacidosis (EDKA) in a 43-year-old woman with type 2 diabetes mellitus who presented to the emergency department with problems of vomiting, cough, shortness of breath and generalised weakness after following a ketogenic diet for 2 weeks. Therapy with sodium glucose transport protein-2 empagliflozin had been started 2 months prior. Initial evaluation revealed high anion gap metabolic acidosis with blood glucose level of 169 mg/dL. Treatment for EDKA with fluid resuscitation, intravenous insulin and dextrose resolved her acidosis and symptoms in less than 24 hours. Empaglifozin was discontinued on discharge. This entity represents a diagnostic challenge since the differential diagnosis is broad with a potentially misleading clinical presentation that can result in delayed diagnosis and adverse outcomes including acute kidney injury, multiple electrolyte abnormalities, cerebral oedema, acute respiratory distress syndrome, shock and death.

Utilizing End-Tidal Carbon Dioxide to Diagnose Diabetic Ketoacidosis in Prehospital Patients with Hyperglycemia.

BACKGROUND: Early identification of diabetic ketoacidosis (DKA) may improve clinical outcomes. Prior studies suggest exhaled end tidal carbon dioxide (ETCO2) provides a non-invasive, real-time method to screen for DKA in the emergency department (ED). METHODS: This a retrospective cohort study among patients who activated Emergency Medical Services (EMS) during a one-year period. Initial out-of-hospital vital signs documented by EMS personnel, including ETCO2 and first recorded blood glucose level (BGL), as well as in-hospital records, including laboratory values and diagnosis, were collected. The main outcome was the association between ETCO2 and the diagnosis of DKA. RESULTS: Of the 118 patients transported with hyperglycemia (defined by BGL >200), six (5%) were diagnosed with DKA. The mean level of ETCO2 in those without DKA was 35mmHg (95% CI, 33-38mmHg) compared to mean levels of 15mmHg (95% CI, 8-21mmHg) in those with DKA (P <.001). The Area Under the Receiver Operating Characteristics (ROC) Curve (AUC) for ETCO2 identifying DKA was 0.96 (95% CI, 0.92-1.00). The correlation coefficient between ETCO2 and serum bicarbonate (HCO3) was 0.436 (P <.001) and the correlation coefficient between ETCO2 and anion gap was -0.397 (P <.001). CONCLUSION: Among patients with hyperglycemia, prehospital levels of ETCO2 were significantly lower in patients with DKA compared to those without and were predictive of the diagnosis of DKA. Furthermore, out-of-hospital ETCO2 was significantly correlated with measures of metabolic acidosis.