Frequency,Clinical Characteristics and Predictors of Ketoacidosis at Diagnosis of Type One Diabetes Mellitus in Children and Adolescents from Jordan

Objective:Data regarding diabetic ketoacidosis (DKA) at diagnosis of type one diabetes (T1D) in developing countries are scarce. The aim of this study was to describe the frequency of DKA at the onset of T1D in children and adolescents in Jordan and to compare the clinical and biochemical characteristics between the group that presented with DKA and the group that did not.Methods:The records of 341 children and adolescents, less than sixteen years of age, who were diagnosed with T1D between 2015 and 2019 were evaluated retrospectively.Results:Of all the children diagnosed with T1D, 108 (31.7%) presented with DKA. The majority had mild or moderate DKA (38% and 33.3% respectively). Higher paternal education levels were associated with a lower probability of presenting with DKA (p=0.043). A family history of T1D had a protective effect on the occurrence of DKA (Odds ratio=2.138; 95% confidence interval=1.167-3.917, p=0.014). Patients with celiac disease and higher HbA1c levels were more likely to experience recurrent episodes of DKA, (p=0.004 and 0.011, respectively).Conclusion:In Jordan, the rate of DKA at presentation of T1D remains high. Prevention campaigns are needed to increase diabetes awareness among the public and healthcare providers.     

Diabetic ketoacidosis in adult patients: an audit of factors influencing time to normalisation of metabolic parameters

Background

Diabetic ketoacidosis (DKA) is an acute life‐threatening metabolic complication of diabetes that imposes substantial burden on our healthcare system. There is a paucity of published data in Australia assessing factors influencing time to resolution of DKA and length of stay (LOS).

Aims

To identify factors that predict a slower time to resolution of DKA in adults with diabetes.

Methods

Retrospective audit of patients admitted to St Vincent's Hospital Melbourne between 2010 to 2014 coded with a diagnosis of ‘Diabetic Ketoacidosis’. The primary outcome was time to resolution of DKA based on normalisation of biochemical markers. Episodes of DKA within the wider Victorian hospital network were also explored.

Results

Seventy‐one patients met biochemical criteria for DKA; median age 31 years (26–45 years), 59% were male and 23% had newly diagnosed diabetes. Insulin omission was the most common precipitant (42%). Median time to resolution of DKA was 11 h (6.5–16.5 h). Individual factors associated with slower resolution of DKA were lower admission pH (P < 0.001) and higher admission serum potassium level (P = 0.03). Median LOS was 3 days (2–5 days), compared to a Victorian state‐wide LOS of 2 days. Higher comorbidity scores were associated with longer LOS (P < 0.001).

Conclusions

Lower admission pH levels and higher admission serum potassium levels are independent predictors of slower time to resolution of DKA. This may assist to stratify patients with DKA using markers of severity to determine who may benefit from closer monitoring and to predict LOS.     

Clinical Characteristics Associated with the Development of Diabetic Ketoacidosis in Patients with Type 2 Diabetes

Objective This study analyzed the clinical and laboratory parameters that might influence the clinical outcomes of patients with type 2 diabetes who develop diabetic ketoacidosis (DKA), which has not been well investigated. Methods We reviewed the clinical and laboratory data of 158 patients who were hospitalized due to DKA between January 2006 and June 2019 and compared the data of patients stratified by the type of diabetes. In addition, the patients with type 2 diabetes were subdivided according to age, and their clinical and laboratory findings were evaluated. Results Patients with type 2 diabetes had a longer symptom duration associated with DKA, higher body mass index (BMI), and higher C-peptide levels than those with type 1 diabetes (p＜0.05). Among patients with type 2 diabetes, elderly patients (≥65 years old) had a longer duration of diabetes, higher frequency of DKA onset under diabetes treatment, higher effective osmolarity, lower BMI, and lower urinary C-peptide levels than nonelderly patients (＜65 years old) (p＜0.05). A correlation analysis showed that age was significantly negatively correlated with the index of insulin secretory capacity. Conclusion Patients with DKA and type 2 diabetes had a higher BMI and insulin secretion capacity than those with type 1 diabetes. However, elderly patients with type 2 diabetes, unlike younger patients, were characterized by a lean body, impaired insulin secretion, and more frequent DKA development while undergoing treatment for diabetes.     

Diabetic ketoacidosis secondary to L‐asparaginase in acute lymphoblastic leukaemia

We describe a case of severe hyperglycaemia resulting in diabetic ketoacidosis secondary to L‐asparaginase. There are few reports of this potentially life‐threatening complication, particularly in the English literature. Awareness and recognition of this preventable and manageable problem will improve safe delivery of this anti‐leukaemic drug.     

Clinical characteristics and outcomes of diabetic ketoacidosis in Pakistani adults with Type 2 diabetes mellitus.

AIMS: The aim of this study was to describe the clinical characteristics and outcomes of diabetic ketoacidosis (DKA) in Pakistani adult population with Type 2 diabetes mellitus. METHODS: We reviewed the medical records of all adult patients admitted with a diagnosis of DKA and Type 2 diabetes mellitus (DM) and followed their clinical course and outcome. Follow-up data were obtained by chart review or telephone contact where necessary. RESULTS: Fifty-seven patients fulfilled criteria for inclusion in the study. Their mean age was 48 +/- 7 years. The mean body mass index was 25.5 +/- 6.2 kg/m2. Forty-nine had a prior history of Type 2 DM but DKA was the initial presentation in 14%. Nine were on no treatment, 40 were using oral hypoglycaemic agents and eight were on insulin. A history of prior DKA was noted in eight patients. Infections were the most common precipitating factor (63%). There were 12 deaths. Follow-up after a period ranging between 12 and 43 months revealed that 30/45 patients remained on OHA without recurrence of DKA. CONCLUSION: This report highlights the need for the growing recognition of DKA occurring in adults with Type 2 DM in the South Asian population. Mortality rates are unacceptably high but the majority of survivors remain insulin independent.     

Childhood diabetes presenting with hyperosmolar dehydration but without ketoacidosis: a report of three cases.

BACKGROUND: Diabetic ketoacidosis (DKA) is a common mode of presentation of diabetes mellitus in children, accounting for 26% of new cases. Rarely, children with diabetes may develop other forms of metabolic decompensation associated with hyperglycaemia and hyperosmolality. Hyperglycaemia and hyperosmolality without ketoacidosis has high mortality in adults, although there is no data on mortality in children. CASE REPORTS: We describe three children who presented to Birmingham Children's Hospital and were initially suspected to have DKA. Each child was severely hyperglycaemic and hyperosmolar but without significant ketosis or acidosis. In two of the three children, the hyperosmolar state was associated with the ingestion of large volumes of high calorie fluids preceding the presentation. These children were exquisitely sensitive to insulin and may be at a significantly higher risk of cerebral oedema in view of their hyperosmolar state. CONCLUSIONS: Hyperosmolar hyperglycaemia is a serious and rare complication at presentation of diabetes in children, and should be distinguished from DKA. These children are at an increased risk of cerebral oedema compared with DKA, and one should have a low threshold for suspicion of this complication.     

A Long-Term Comparison of Presenting Characteristics of Children with Newly Diagnosed Type 1 Diabetes Before and During the COVID-19 Pandemic

Objective:Diabetic ketoacidosis (DKA) - a potentially preventable complication of type 1 diabetes mellitus (T1D) - is one of the most common chronic childhood diseases, and is associated with a significant risk of morbidity and mortality. The limited use of healthcare services due to fear of Coronavirus disease-2019 (COVID-19) transmission during the pandemic has raised concerns of delays in T1D diagnosis, among other diseases. This study investigated the presenting characteristics of newly diagnosed T1D patients assessed in a single clinic during the pandemic and compares them with the pre-pandemic period.Methods:For the purpose of this study, the first year of the pandemic is referred to as the “pandemic period”, and the previous three years as the “pre-pandemic period”. Patient files were reviewed retrospectively, the demographic and clinical characteristics and laboratory findings of the patients were recorded, and the findings from both periods were compared.Results:The number of patients diagnosed with T1D in the pandemic period was 44, and in the pre-pandemic period 39 in 2017, 22 in 2018 and 18 in 2019. The two groups had similar age, sex, pubertal stage and anthropometric characteristics (p>0.05). Regarding the type of presentation, the frequency of DKA was significantly higher in the pandemic period (68.2%) than in the pre-pandemic period (40.5%) (p=0.006), and this difference was also observed in the comparison by years (p=0.016). The duration of symptoms (16.5±10.7 vs. 23.5±17.6 days) and the length of hospital stay (10±3.9 vs. 15.2±5.5 days) were significantly shorter in the pandemic period (p=0.032, and p<0.001, respectively). There was no difference in the frequency of severe DKA between the pandemic (46.7%) and the pre-pandemic (37.5%) periods (p>0.05). However, pH (7.17±0.16 vs. 7.26±0.14) and bicarbonate (12.8±6.3 vs. 16.6±6.3) levels were significantly lower in the pandemic period (p<0.005). Additional signs of infection on admission were less frequent in the pandemic period (9.1%) than in the pre-pandemic period (27.8%) (p=0.027). The groups did not differ in terms of hemoglobin A1c, C-peptide, concurrent thyroid autoantibodies and tissue transglutaminase antibodies (p>0.05). The rate of anti-glutamic acid decarboxylase positivity was higher in the pandemic period (73.8% vs. 39.2%) (p=0.001) while the frequency of other diabetes-associated autoantibodies was similar between the groups (p>0.05). The polymerase chain reaction test for COVID-19 was negative in six patients with a history of contact.Conclusion:There was an increased frequency and severity of DKA in children with newly diagnosed T1D in the pandemic period, and these findings justify concerns related to the diagnosis of other diseases during the pandemic. Studies to raise awareness of diabetes symptoms during the pandemic should be continued regularly to reach all segments of society. Our study provides an additional contribution to the literature in its coverage of the one-year period during the pandemic and its comparison with the previous three years.     

Hyperglycaemic symptoms before diagnosis of non-insulin-dependent (type 2) diabetes mellitus in relation to 5-year outcome.

A group of newly diagnosed patients with non-insulin-dependent (type 2) diabetes mellitus (n = 133) were divided into two groups according to the symptoms of diabetes mellitus at diagnosis; a group (26 men and 17 women) with hyperglycaemic symptoms (polydipsia, polyuria, weight loss and tiredness) and a group (44 men and 46 women) without such symptoms. At the time of diagnosis, symptomatic patients tended to be leaner (P = NS), and they were more hyperglycaemic (P less than 0.001-0.06) and had lower insulin responses to an oral glucose load (P less than 0.01-0.05) than asymptomatic patients, but after 5 years no difference in these respects was found. No significant differences in the frequency of islet-cell antibodies or cardiovascular diseases were found between the two diabetic groups. At the 5-year examination, the initially symptomatic patients were receiving pharmacological treatment for hyperglycaemia more often than asymptomatic patients. No consistent differences in clinical characteristics and 5-year outcome were observed between those diabetic patients who were diagnosed on the basis of hyperglycaemic symptoms and those who were diagnosed for other reasons. In conclusion, in middle-aged patients with newly diagnosed diabetes mellitus classified as non-insulin-dependent, diabetic symptoms at diagnosis did not predict the 5-year outcome of the patients in terms of metabolic control or cardiovascular events.     

Practical management of diabetic ketoacidosis and hyperosmolar coma

In diabetic ketoacidosis (DKA) and particularly in hyperosmolar coma, rapid normalisation of the measured extracellular fluid abnormalities cannot be equated with optimal management. In both disorders there are complex imbalances between extra- and intracellular compartments that are best corrected in a series of rational steps, based on an understanding of pathophysiology. Fluid administration in DKA can generally be divided into three successive phases: (i) a short period of rapid isotonic saline infusion, (ii) slower infusion of isotonic saline with potassium chloride, and (iii) glucose-potassium infusion until oral food intake is well established. In severe cases, there is a definite place for judicious use of isotonic sodium bicarbonate in small amounts. While insulin infusion is desirable, intramuscular insulin remains a satisfactory alternative. Biochemical monitoring is mandatory and management must be reviewed and modified every three to four hours on the basis of the clinical and biochemical response. In the management of hyperosmolar coma, insulin and fluid therapy are more conservative, with the aim of achieving complete rehydration and normoglycaemia only after 36 to 72 hours. Pulmonary complications and the effects of tissue ischaemia, as well as thromboembolic events, remain important causes of death in both disorders. The frequent recurrences of DKA that occur in a group of psychiatrically-unstable young patients remain an unsolved problem.     

Characteristics of young adults with multiple episodes of diabetic ketoacidosis

Transition from paediatric to adult diabetes care can be associated with a deterioration in metabolic control and hospitalisation. This was a retrospective review (2012–2016) of medical records of all patients attending a transition diabetes clinic in a teaching hospital with paediatric and adult diabetes on the same site. Among the 91/102 (89.2%) patients with type 1 diabetes, mean age at first visit was 19 ± 2 years, last body mass index was 25.2 ± 4.7 kg/m², diabetes duration was 11 ± 6 years and 22 (24%) used continuous subcutaneous insulin infusions. Loss to follow‐up was 15 (14.7%). Mental health issues were common (59%), as were prior pregnancies (23%) and diabetic ketoacidosis since diagnosis (39%). Those with diabetic ketoacidosis had a higher mean glycated haemoglobin (70 ± 19 vs 86 ± 25 mmol/mol or 8.6 ± 1.7 vs 10.0 ± 2.3%; P = 0.001), fewer clinic attendances (8 ± 5 vs 5 ± 4; P = 0.008) and fewer years in clinic (1.8 ± 1.7 vs 2.3 ± 1.4; P = 0.114). Our data suggest that investment in joint approaches with mental health services should be considered.     

A transition care programme which improves diabetes control and reduces hospital admission rates in young adults with Type 1 diabetes aged 15-25 years.

AIMS: To determine if a transition support programme for young adults with diabetes could maintain attendance at a specialist clinic, improve diabetes control and reduce acute hospital admissions with diabetic ketoacidosis (DKA) in 15-25-year-olds with Type 1 diabetes. METHODS: A transition coordinator/diabetes educator arranged booking and rebooking of appointments for a young adult diabetes clinic based in an adult hospital between July 2001 and March 2006. An after-hours phone support service was initiated. Data collected included source of referral, frequency of clinic attendance and HbA1c at each visit. Numbers of admissions and readmissions with DKA, length of stay and HbA1c on admission were recorded. RESULTS: One hundred and ninety-one young adults were referred. HbA1c at initial referral was 9.3 +/- 2.17%. HbA1c significantly improved to 8.8 +/- 1.9% (P < 0.001) after a median of five visits with a statistically significant fall in HbA1c of 0.13% per visit (P = 0.01). The greatest improvements were seen in those with starting HbA1c > 11% (-2.5 +/- 2.3%, P < 0.001). Eighty-two percent had attended appointments in the last 6 months. There was a significant reduction in DKA admissions falling by 1/3 (P = 0.05), and in readmissions a significant reduction in length of stay (-3.6 days, P = 0.02), over 3.5 years. CONCLUSIONS: If young adults are appropriately supported in adult services, clinic attendance is maintained, diabetes control is improved and hospital admission rates with DKA are reduced. The cost savings from reduced admissions covered the costs of the programme.     

Positive troponin in diabetic ketoacidosis without evident acute coronary syndrome predicts adverse cardiac events

BACKGROUND: Elevated troponin I has been associated with increased mortality in critically ill patients without acute coronary syndrome (ACS). However, the prognostic significance of troponin elevation in patients with diabetic ketoacidosis (DKA) without evident ACS has not been studied. METHODS: Retrospective study of all patients admitted to a U.S. tertiary center between 01/98 and 12/00 with DKA and had troponin I level measured. Patients with evidence of ACS or who met the American College of Cardiology/European Society of Cardiology (ACC/ESC) definition for myocardial infarction were excluded. Baseline characteristics, cardiac evaluation and 2 year major adverse coronary event (MACE) rate were compared between patients with positive and negative troponin. RESULTS: Ninety-six patients fulfilled the inclusion criteria of this study, 26 had positive troponin. There were no differences in baseline characteristics between the two groups. After a 2 year follow-up, there was significantly increased mortality in patients with elevated troponin (50.0% versus 27.1%, hazard-ratio (HR) 2.3, 95% confidence interval (CI) 1.2-4.8, p = 0.02). Patients with elevated troponin also had significantly increased MACE rate at 2 years (50.0% versus 28.6%, HR 2.6, 95% CI 1.3-5.3, p = 0.007) driven primarily by mortality. Using Cox Proportional Hazard Analysis, elevated troponin was a predictor of increased MACE after adjusting for confounding variables. (Adjusted HR 2.3, 95% CI 1.1-4.6, p = 0.02) CONCLUSIONS: Elevated troponin I in diabetic patients admitted with DKA identifies a group at very high risk for future cardiac events and mortality. Whether cardiac risk stratification of these patients will improve long term outcome remains to be studied.     

Clinical profile and outcomes in COVID-19 patients with diabetic ketoacidosis: A systematic review of literature

Background and aimTo conduct a systematic literature review and analyze the demographic/biochemical parameters and clinical outcomes of COVID-19 patients with diabetic ketoacidosis (DKA) and combined DKA/HHS (hyperglycemic hyperosmolar syndrome).MethodsPubMed, Scopus, Embase, and Google Scholar databases were systematically searched till August 3, 2020 to identify studies reporting COVID-19 patients with DKA and combined DKA/HHS. A total of 19 articles reporting 110 patients met the eligibility criteria.ResultsOf the 110 patients, 91 (83%) patients had isolated DKA while 19 (17%) had DKA/HHS. The majority of the patients were male (63%) and belonged to black ethnicity (36%). The median age at presentation ranged from 45.5 to 59.0 years. Most of the patients (77%) had pre-existing type 2 diabetes mellitus. Only 10% of the patients had newly diagnosed diabetes mellitus. The median blood glucose at presentation ranged from 486.0 to 568.5 mg/dl, being higher in patients with DKA/HHS compared to isolated DKA. The volume of fluid replaced in the first 24 h was higher in patients with DKA/HHS in contrast to patients with DKA alone. The in-hospital mortality rate was 45%, with higher mortality in the DKA/HHS group than in the isolated DKA group (67% vs. 29%). pH was lower in patients who had died compared to those who were discharged.ConclusionDKA in COVID-19 patients portends a poor prognosis with a mortality rate approaching 50%. Differentiating isolated DKA from combined DKA/HHS is essential as the latter represents nearly one-fifth of the DKA cases and tends to have higher mortality than DKA alone.     

Evidence-based management of hyperglycemic emergencies in diabetes mellitus

The hyperglycemic emergencies, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are potentially fatal complications of uncontrolled diabetes mellitus. The incidence of DKA and the economic burden of its treatment continue to rise, but its associated mortality rate which was uniformly high has diminished remarkably over the years. This Improvement in outcome is largely due to better understanding of the pathogenesis of hyperglycemic emergencies and the application of evidence-based guidelines in the treatment of patients. In this article, we present a critical review of the evidence behind the recommendations that have resulted in the improved prognosis of patients with hyperglycemic crises. A succinct discussion of the pathophysiology and important etiological factors in DKA and HHS are provided as a prerequisite for understanding the rationale for the effective therapeutic maneuvers employed in these acute severe metabolic conditions. The evidence for the role of preventive measures in DKA and HHS is also discussed. The unanswered questions and future research needs are also highlighted.     

Sodium-glucose co-transporter inhibitors,their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol

Recent phase 3 clinical trials have evaluated the impact of adding sodium-glucose co-transporter (SGLT) inhibitors to the type 1 diabetes armamentarium. These trials studied SGLT2 inhibitors (dapagliflozin and empagliflozin) and a dual SGLT1 and SGLT2 inhibitor (sotagliflozin), and demonstrated that these oral non-insulin antihyperglycaemic medications are able not only to improve glycaemic control, but also to reduce body weight and extend time in range without increasing rates of hypoglycaemia in type 1 diabetes. Diabetic ketoacidosis (DKA) is a feature of type 1 diabetes and the risk is increased when SGLT inhibitors are used in type 1 diabetes. To minimize the risk of DKA and still gain the multiple benefits, we developed the “STOP DKA Protocol “, an easily accessible and practical tool, that provides a risk mitigation strategy for reducing DKA in patients with type 1 diabetes being treated with SGLT inhibitors.