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1.  Clinical profile and outcomes of adult patients with hyperglycemic emergencies managed at a tertiary care hospital in Nigeria 
To document the clinical profile and treatment outcomes of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) managed in a tertiary care hospital.
Materials and Methods:
This was a retrospective review of hospital records of patients with DKA and HHS admitted to a tertiary care hospital over a 24-month period. Data on demographics, precipitating factors, clinical features, serum electrolytes, duration of hospital admission, and mortality were extracted.
Eighty-four patients were included in the study. Fifty (59.5%) were females. Ten (11.9%) persons had type 1 diabetes mellitus (T1DM) and 74 (88.1%) had type 2 diabetes mellitus (T2DM). There were 35 cases of DKA and 49 cases of HHS. Nine patients with T1DM presented in DKA and one in HHS. Forty-eight (55.2%) subjects were previously not diagnosed of diabetes mellitus (DM). The mean±SEM age, casual blood glucose, calculated serum osmolality, and duration of hospital stay of the study subjects were 50.59±1.63 years, 517.98±11.69 mg/dL, 313.59±1.62 mOsmol/L, and 18.85±1.78 days, respectively. Patients with T2DM were significantly older than those with T1DM (54.32±1.34 vs. 23.40±1.38 years, P<0.001).The precipitating factors were poor drug compliance 23 (27.4%), malaria 12 (14.3), urinary tract infection 10 (11.9%), lobar pneumonia 4 (4.8%), and unidentifiable in 29 (34.5%). Common electrolyte derangements were hyponatremia, 31 (36.9%) and hypokalemia 21 (25%). Mortality rate was 3.6%.
DKA is common in patients with T2DM.Over 50% of the patients presenting with DKA or HHS have no previous diagnosis of DM. Non-compliance, malaria, and infections are important precipitants. Mortality rate is low.
PMCID: PMC3531028  PMID: 23293409
Diabetic ketoacidosis; hyperosmolar hyperglycemic state; precipitating factors
2.  Can APACHE II Score Predict Diabetic Ketoacidosis in Hyperglycemic Patients Presenting to Emergency Department? 
Diabetic ketoacidosis (DKA) is an acute and life-threatening complication in diabetic patients. The current diagnostic criteria of DKA are metabolic acidosis, blood glucose level greater than 250 mg/dL and the presence of ketones in serum or urine. DKA patients referring to the emergency department (ED) are usually ill.
The present study aims to evaluate the efficacy of Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring in predicting the critically illness in the hyperglycemic patients referring to the ED.
Patients and Methods:
We performed a prospective cohort study in an ED. One hundred eighty one patients older than 18 years with hyperglycemia were included in our study. Following the primary evaluation, the subjects were divided into DKA and non-DKA patients. APACHE II scores were calculated for all patients and then compared to each other. We determined predictive value, sensitivity, specificity and cut-off points of APACHE II score for DKA.
Sixty two patients had DKA. The comparison of APACHE II score among two groups of the patients did not show any significant difference (P = 0.597). There was no suitable cut-off point for APACHE II score to predict DKA.
APACHE II score cannot be applied in the predicting of DKA in hyperglycemic patients admitted in ED.
PMCID: PMC4286803  PMID: 25599026
Diabetic Ketoacidosis; APACHE II; Emergency Department
3.  Frequency of Ketoacidosis in Newly Diagnosed Type 1 Diabetic Children 
Oman Medical Journal  2010;25(2):114-117.
Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM). Many patients with newly diagnosed type 1 diabetes present with DKA. The aim of this study is to determine the frequency and the clinical presentation of diabetic ketoacidosis at the diagnosis of type 1 diabetes mellitus in youths in hamadan, Western Province of Iran.
The Clinical and laboratory data of a total of 200 patients under 19 years of age with newly diagnosed type 1 diabetes mellitus between 1995-2005 were retrospectively reviewed. Statistical analysis was performed using SPSS 11.
48 (24%)of the children were presented in a state of ketoacidosis. Sever form of DKA (pH≤7.2) was observed in 54.5% of patients. The mean age at diagnosis was 7.3±5.15 years in DKA group and 8.59±3.07 in non-DKA group (p=0.22). 60.4% of patient with DKA were female whereas in the non-DKA group, 53.3% of patients were female, the difference was not significant (p=0.38). The duration of symptoms before diagnosis was 14.84±8.19 days in patients with DKA and 22.39±2.27 in the non-DKA group, (p=0.11). No significant difference was found between the age, sex and duration of the symptoms and occurance of DKA. Polydipsia (85.4) polyuria (83.3%), weakness (68.8%) and abdominal pain (52.1%) were the most frequently notified symptoms among the patients. In two cases, diagnosis of DKA was preceded by as appendicitis and the patient underwent appendectomy.
Frequency of DKA at onset of type 1 diabetes mellitus was significant in the studied region. However, it was lower than other regions in Asia. Polydipsia, polyuria, fatigue and abdominal pain were the most common symptoms on presentation.
PMCID: PMC3215499  PMID: 22125712
4.  Treatment outcome and prognostic indices in patients with hyperglycemic emergencies 
The objective of this study is to assess the treatment outcomes in patients with hyperglycemic emergencies and to ascertain the factors associated with outcome, with emphasis on the determinants of outcome.
A total of 105 patients admitted to the Accident and Emergency unit, who fulfilled the criteria for hyperglycemic emergencies, were selected. The information extracted included sociodemographic, clinical, and laboratory data, as well as hospitalization outcome.
Of the 105 subjects that participated in the study, hyperosmolar hyperglycemic nonketotic state (HHNK) was seen in 50% (53) of the subjects, while diabetic ketoacidosis (DKA) was seen in 31% (29), normo-osmolar nonketotic hyperglycemic state (NNHS) in 12% (13), and mixed hyperglycemic emergency in 7% (10) of the subjects. The overall mortality rate in this study was 4.8%. Three deaths were recorded in patients with HHNK, while DKA and NNHS each had one death. Three of the deaths occurred within the first 24 hours of admission while the other two were more than 24 hours after admission. The mean (standard deviation) total duration of hospital stay was 24.2 days (SD), and the range of stay was 0.5–88 days.
The most common type of hyperglycemic emergency seen in this study was HHNK. Also, the presence of infection, and sex of the study subject, were significant determinants of outcome in this study.
PMCID: PMC3749816  PMID: 23983480
hyperglycemia; emergency; diabetes mellitus; insulin
5.  Epidemiological characteristics of ketoacidosis among Korean diabetic patients. 
An epidemiological study on diabetic ketoacidosis (DKA) was done by analysis of 207 cases collected from the medical records of 6 major general hospitals in Seoul area during the period of 5 years between 1979 and 1984. There was female predominance in the occurrence of DKA (male/female ratio, 0.71) in spite of the male predominance in general prevalence of diabetes mellitus (1.80). This female predominance in DKA was most striking in the age group under 40. There was a significant seasonal variation in the occurrence of DKA. DKA occurred most frequently in colder season with the highest peak in December. In July and August, the hottest season in Korea, not even a single case of DKA was recorded in this series. No discernible precipitating factor was found in 39.3% of DKA cases and infections was present as a cause of DKA in 30% of cases. In 27.5%, DKA was the first clinical presentation of diabetes and in the remainders of cases, diabetes was known to be present for average of 6.4 years. Mortality of DKA was 13.2% in this series. As to the socioeconomic status, the education level, the style of living and the duration of diabetes, there were not ascertainable differences between the DKA cases and other diabetic cases. The prospective epidemiological study of diabetic population in Korea, especially in female group, would be necessary for elucidation of the characteristics of DKA in Koreans such as the female predominance and the seasonal difference of the occurrence.
PMCID: PMC3053633  PMID: 3151981
6.  Endocrine-related diseases in the emergency unit of a Tertiary Health Care Center in Lagos: A study of the admission and mortality patterns 
Non-communicable diseases are emerging as an important component of the burden of diseases in developing countries. Knowledge on admission and mortality patterns of endocrine-related diseases will give insight into the magnitude of these conditions and provide effective tools for planning, delivery, and evaluation of health-care needs relating to endocrinology.
Materials and Methods:
We retrieved medical records of patients that visited the emergency unit of the Lagos University Teaching hospital, over a period of 1 year (March 2011 to February 2012) from the hospital admissions and death registers. Information obtained included: Age, gender, diagnosis at admission and death, co-morbidities. Diagnoses were classified as endocrine-related and non-endocrine related diseases. Records with incomplete data were excluded from the study.
A total of 1703 adult medical cases were seen; of these, 174 were endocrine-related, accounting for 10.2% of the total emergency room admission in the hospital. The most common cause of endocrine-related admission was hyperglycaemic crises, 75 (43.1%) of cases; followed by diabetes mellitus foot syndrome, 33 (19.0%); hypoglycaemia 23 (13.2%) and diabetes mellitus related co-morbidities 33 (19.0%). There were 39 endocrine-related deaths recorded. The result revealed that 46.1% of the total mortality was related to hyperglycaemic emergencies. Most of the mortalities were sepsis-related (35.8%), with hyperglycaemic crises worst affected (71.42%). However, the case fatalities were highest in subjects with thyrotoxic crisis and hypoglycaemic coma.
Diabetic complications were the leading causes of endocrine-related admissions and mortality in this health facility. The co-morbidity of sepsis and hyperglycaemia may worsen mortality in patients who present with hyperglycaemic crises. Hence, evidence of infection should be sought early in such patients and appropriate therapy instituted.
PMCID: PMC3821227  PMID: 24249952
Admissions; diabetes; endocrine-related diseases; hyperglycaemia; hypoglycaemia emergency; mortality
7.  Hyperglycemic emergencies in Indian patients with diabetes mellitus on pilgrimage to Amarnathji yatra 
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) represent two distinct metabolic derangements manifested by insulin deficiency and severe hyperglycemia, with estimated mortality rates of 2.5–9%. In patients with type 2 diabetes mellitus (DM) controlled by diet or oral agents, DKA does not occur unless there is significant severe stress such as severe sepsis, major surgery, trauma, etc. We observed many such emergencies occurring in pilgrims.
We analyzed the data of 13 patients with DM admitted in our endocrine department with hyperglycemic emergencies during 2 years of the annual pilgrimage (yatra) to Amarnathji.
Materials and Methods:
We reviewed and analyzed the case records of 13 yatris with DM who were referred and admitted in our hospital with hyperglycemic emergencies during the yatra season (July–August) of 2006 and 2007.
Eleven of 13 had DKA and 1 each had HHS and hypoglycemia. After initial clinical assessment and blood sampling for blood counts, electrolytes, blood gases, urinalysis, chest radiography, and electrocardiography, these cases were managed with standard protocol published by American Diabetes Association (ADA) for the management of DKA and HHS. Average blood glucose was 466 mg/dl and nine subjects had moderate to severe ketonuria. All the cases, except one, were in stable condition at the time of discharge.
High altitude, strenuous exertion of going uphill, withdrawal of insulin or oral hypoglycemic drugs, starvation, sepsis, and alcohol intake were recorded as predisposing factors. Therefore, there is an immense need for institution of a special health education program to all the yatris before taking the endeavor.
PMCID: PMC3354951  PMID: 22701854
Amarnath shrine; diabetic ketoacidosis; high altitude climbing; starvation; type 2 diabetes mellitus
8.  Stroke and diabetic ketoacidosis – some diagnostic and therapeutic considerations 
Cerebrovascular insult (CVI) is a known and important risk factor for the development of diabetic ketoacidosis (DKA); still, it seems that the prevalence of DKA among the patients suffering CVI and its influence on stroke outcome might be underestimated. Diabetic ketoacidosis itself has been reported to be a risk factor for the occurrence of stroke in children and youth. A cerebral hypoperfusion in untreated DKA may lead to cerebral injury, arterial ischemic stroke, cerebral venous thrombosis, and hemorrhagic stroke. All these were noted following DKA episodes in children. At least some of these mechanisms may be operative in adults and complicate the course and outcome of CVI. There is a considerable overlap of symptoms, signs, and laboratory findings in the two conditions, making their interpretation difficult, particularly in the elderly and less communicative patients. Serum pH and bicarbonate, blood gases, and anion gap levels should be routinely measured in all type 1 and type 2 diabetics, regardless of symptomatology, for the early detection of existing or pending ketoacidosis. The capacity for rehydration in patients with stroke is limited, and the treatment of the cerebrovascular disease requires intensive use of osmotic and loop diuretics. Fluid repletion may be difficult, and the precise management algorithms are required. Intravenous insulin is the backbone of treatment, although its effect may be diminished due to delayed fluid replenishment. Therefore, the clinical course of diabetic ketoacidosis in patients with CVI may be prolonged and complicated.
PMCID: PMC3986295  PMID: 24748799
CVI; type 2 diabetes complications; acid-base disturbances; fluid management
9.  Positive predictive value of automated database records for diabetic ketoacidosis (DKA) in children and youth exposed to antipsychotic drugs or control medications: a tennessee medicaid study 
Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of treatment with some atypical antipsychotic drugs in children and youth. Because drug-associated DKA is rare, large automated health outcomes databases may be a valuable data source for conducting pharmacoepidemiologic studies of DKA associated with exposure to individual antipsychotic drugs. However, no validated computer case definition of DKA exists. We sought to assess the positive predictive value (PPV) of a computer case definition to detect incident cases of DKA, using automated records of Tennessee Medicaid as the data source and medical record confirmation as a "gold standard."
The computer case definition of DKA was developed from a retrospective cohort study of antipsychotic-related type 2 diabetes mellitus (1996-2007) in Tennessee Medicaid enrollees, aged 6-24 years. Thirty potential cases with any DKA diagnosis (ICD-9 250.1, ICD-10 E1x.1) were identified from inpatient encounter claims. Medical records were reviewed to determine if they met the clinical definition of DKA.
Of 30 potential cases, 27 (90%) were successfully abstracted and adjudicated. Of these, 24 cases were confirmed by medical record review (PPV 88.9%, 95% CI 71.9 to 96.1%). Three non-confirmed cases presented acutely with severe hyperglycemia, but had no evidence of acidosis.
Diabetic ketoacidosis in children and youth can be identified in a computerized Medicaid database using our case definition, which could be useful for automated database studies in which drug-associated DKA is the outcome of interest.
PMCID: PMC3235973  PMID: 22112194
10.  Thyroid storm associated with Graves' disease covered by diabetic ketoacidosis: A case report 
Thyroid Research  2011;4:8.
Thyroid storm is a condition in which multiple organ dysfunction results from failure of the compensatory mechanisms of the body owing to excessive thyroid hormone activity induced by some factors in patients with thyrotoxicosis. While diabetic ketoacidosis (DKA) is an important trigger for thyroid storm, simultaneous development of DKA and thyroid storm is rare.
Case presentation
A 59-year-old woman with no history of either diabetes mellitus or thyroid disease presented to our hospital because of developing nausea, vomiting and diarrhea for 2 days. Physical examination showed mild disturbance of consciousness, fever, and tachycardia. There were no other signs of thyrotoxicosis. Laboratory studies revealed elevation of random blood glucose and glycosylated hemoglobin, strongly positive of urine acetone, and metabolic acidosis. Since DKA was diagnosed, we initiated the patient on treatment with administration of insulin and adequate fluid replacement. Although the hyperglycemia and acidosis were immediately relieved, the disturbance of consciousness and tachycardia remained persistent. Levels of FT3 and FT4 were extremely high and TSH was below the detectable limit. TRAb was positive. The thyroid storm score of Burch & Wartofsky was 75/140, and the thyroid storm diagnostic criteria of the Japan Thyroid Association were satisfied. Oral administration of thiamazole, potassium iodide and propranolol resulted in immediate relief of the tachycardia.
We encountered a case of thyroid storm associated with Graves' disease covered by DKA. Thyroid storm and DKA are both potentially fatal, and the prognosis varies depending on whether or not these conditions are detected and treated sufficiently early. The thyroid storm diagnostic criteria prepared in 2008 by the Japan Thyroid Association are very simple as compared to the Burch & Wartofsky scoring system for thyroid storm. The Japanese criteria may be useful in the diagnosis of this condition since they enable clinicians to identify a broad range of cases with thyroid storm. When dealing with cases of DKA or thyroid storm, it seems essential to bear in mind the possibility of the coexistence of these two diseases.
PMCID: PMC3094317  PMID: 21492449
11.  Pediatric Diabetic Ketoacidosis, Fluid Therapy and Cerebral Injury: The Design of a Factorial Randomized Controlled Trial 
Pediatric diabetes  2013;14(6):435-446.
Treatment protocols for pediatric diabetic ketoacidosis (DKA) vary considerably among centers in the United States and worldwide. The optimal protocol for intravenous fluid administration is an area of particular controversy, mainly in regard to possible associations between rates of intravenous fluid infusion and the development of cerebral edema, the most common and most feared complication of DKA in children. Theoretical concerns about associations between osmotic fluid shifts and cerebral edema have prompted recommendations for conservative fluid infusion during DKA. However, recent data suggest that cerebral hypoperfusion may play a role in cerebral injury associated with DKA. Currently there are no existing data from prospective clinical trials to determine the optimal fluid treatment protocol for pediatric DKA. The Pediatric Emergency Care Applied Research Network FLUID (Fluid Therapies Under Investigation in DKA) Study is the first prospective randomized trial to evaluate fluid regimens for pediatric DKA. This 13-center nationwide factorial-design study will evaluate the effects of rehydration rate and fluid sodium content on neurological status during DKA treatment, the frequency of clinically-overt CE, and long-term neurocognitive outcomes following DKA.
PMCID: PMC3687019  PMID: 23490311
The mortality and morbidity of acute metabolic complications of diabetes, particularly DKA and HHS are unacceptably high in Nigeria. Prevention of occurrence of these hyperglycaemic emergencies (HE) is the only rational way for a resource poor country like Nigeria. Prevention requires careful identification of precipitating factors of HE. The leading precipitating factors of HE in Nigeria are infections, inadequate or inappropriate use of anti-diabetic agents, especially insulin. HE may also be the first presentation in persons previously unknown to have diabetes. Measures to prevent HE include creation of awareness in the public, effective and systematic education of the persons living with diabetes and capacity building and manpower development of the healthcare personnel. There should be critical appraisal of our healthcare system with a view to restructuring so it can be more accessible to patients and can deliver quality diabetes care. Finally government must sincerely provide an alternative of healthcare financing for the citizens, especially those living with chronic medical conditions like diabetes.
PMCID: PMC4111001  PMID: 25161450
13.  The management of diabetic ketoacidosis in children 
Diabetes Therapy  2011;1(2):103-120.
The object of this review is to provide the definitions, frequency, risk factors, pathophysiology, diagnostic considerations, and management recommendations for diabetic ketoacidosis (DKA) in children and adolescents, and to convey current knowledge of the causes of permanent disability or mortality from complications of DKA or its management, particularly the most common complication, cerebral edema (CE). DKA frequency at the time of diagnosis of pediatric diabetes is 10%–70%, varying with the availability of healthcare and the incidence of type 1 diabetes (T1D) in the community. Recurrent DKA rates are also dependent on medical services and socioeconomic circumstances. Management should be in centers with experience and where vital signs, neurologic status, and biochemistry can be monitored with sufficient frequency to prevent complications or, in the case of CE, to intervene rapidly with mannitol or hypertonic saline infusion. Fluid infusion should precede insulin administration (0.1 U/kg/h) by 1–2 hours; an initial bolus of 10–20 mL/kg 0.9% saline is followed by 0.45% saline calculated to supply maintenance and replace 5%–10% dehydration. Potassium (K) must be replaced early and sufficiently. Bicarbonate administration is contraindicated. The prevention of DKA at onset of diabetes requires an informed community and high index of suspicion; prevention of recurrent DKA, which is almost always due to insulin omission, necessitates a committed team effort.
PMCID: PMC3138479  PMID: 22127748
adolescents; cerebral edema; children; complications; diabetic ketoacidosis; fluid replacement; hypokalemia; management; prevention; recurrent DKA
14.  The management of diabetic ketoacidosis in children 
Diabetes Therapy  2011;1(2):103-120.
The object of this review is to provide the definitions, frequency, risk factors, pathophysiology, diagnostic considerations, and management recommendations for diabetic ketoacidosis (DKA) in children and adolescents, and to convey current knowledge of the causes of permanent disability or mortality from complications of DKA or its management, particularly the most common complication, cerebral edema (CE). DKA frequency at the time of diagnosis of pediatric diabetes is 10%–70%, varying with the availability of healthcare and the incidence of type 1 diabetes (T1D) in the community. Recurrent DKA rates are also dependent on medical services and socioeconomic circumstances. Management should be in centers with experience and where vital signs, neurologic status, and biochemistry can be monitored with sufficient frequency to prevent complications or, in the case of CE, to intervene rapidly with mannitol or hypertonic saline infusion. Fluid infusion should precede insulin administration (0.1 U/kg/h) by 1–2 hours; an initial bolus of 10–20 mL/kg 0.9% saline is followed by 0.45% saline calculated to supply maintenance and replace 5%–10% dehydration. Potassium (K) must be replaced early and sufficiently. Bicarbonate administration is contraindicated. The prevention of DKA at onset of diabetes requires an informed community and high index of suspicion; prevention of recurrent DKA, which is almost always due to insulin omission, necessitates a committed team effort.
PMCID: PMC3138479  PMID: 22127748
adolescents; cerebral edema; children; complications; diabetic ketoacidosis; fluid replacement; hypokalemia; management; prevention; recurrent DKA
15.  Variation in use of intensive care for adults with diabetic ketoacidosis* 
Critical care medicine  2012;40(7):2009-2015.
Intensive care unit (ICU) beds are limited, yet few guidelines exist for triage of patients to the ICU, especially patients at low-risk for mortality. The frequency with which low-risk patients are admitted to ICUs in different hospitals is unknown. Our objective was to assess variation in use of intensive care for patients with diabetic ketoacidosis (DKA), a common condition with a low-risk of mortality.
Observational study using the New York State Inpatient Database (2005-2007).
159 New York State acute care hospitals.
15,994 adult (≥18) hospital admissions with a primary diagnosis of DKA (ICD-9-CM 250.1x).
Measurements and Main Results
We calculated reliability- and risk-adjusted ICU utilization, hospital length of stay (LOS), and mortality. We identified hospital-level factors associated with increased likelihood of ICU admission after controlling for patient characteristics using multilevel mixed-effects logistic regression analyses; we assessed the amount of residual variation in ICU utilization using the intra-class correlation coefficient. Use of intensive care for DKA patients varied widely across hospitals (adjusted range: 2.1% to 87.7%), but was not associated with hospital LOS or mortality. After multilevel adjustment, hospitals with a high volume of DKA admissions admitted DKA patients to the ICU less often (OR 0.40, p=0.002, highest quintile compared to lowest) whereas hospitals with higher rates of ICU utilization for all non-DKA inpatients admitted DKA patients to the ICU more frequently (OR 1.31, p=0.001, for each additional ten percent increase). In the multi-level model, more than half (58%) of the variation in ICU admission practice attributable to hospitals remained unexplained.
We observed variation across hospitals in use of intensive care for DKA patients that was not associated with differences in hospital LOS or mortality. Institutional practice patterns appear to impact admission decisions and represent a potential target for reduction of resource utilization in higher use institutions.
PMCID: PMC3561634  PMID: 22564962
Diabetic Ketoacidosis; Delivery of Health Care; Physician’s Practice Patterns
16.  Risk factors for mortality in children with diabetic keto acidosis from developing countries 
World Journal of Diabetes  2014;5(6):932-938.
Diabetic keto acidosis (DKA) is the major cause for mortality in children with Diabetes mellitus (DM). With increasing incidence of type 1 DM worldwide, there is an absolute increase of DM among children between 0-14 year age group and overall incidence among less than 30 years remain the same. This shift towards younger age group is more of concern especially in developing countries where mortality in DKA is alarmingly high. Prior to the era of insulin, DKA was associated with 100% mortality and subsequently mortality rates have come down and is now, 0.15%-0.31% in developed countries. However the scenario in developing countries like India, Pakistan, and Bangladesh are very different and mortality is still high in children with DKA. Prospective studies on DKA in children are lacking in developing countries. Literature on DKA related mortality are based on retrospective studies and are very recent from countries like India, Pakistan and Bangladesh. There exists an urgent need to understand the differences between developed and developing countries with respect to mortality rates and factors associated with increased mortality in children with DKA. Higher mortality rates, increased incidence of cerebral edema, sepsis, shock and renal failure have been identified among DKA in children from developing countries. Root cause for all these complications and increased mortality in DKA could be delayed diagnosis in children from developing countries. This necessitates creating awareness among parents, public and physicians by health education to identify symptoms of DM/DKA in children, in order to decrease mortality in DKA. Based on past experience in Parma, Italy it is possible to prevent occurrence of DKA both in new onset DM and in children with established DM, by simple interventions to increase awareness among public and physicians.
PMCID: PMC4265883  PMID: 25512799
Diabetic keto acidosis; Mortality; Cerebral edema; Sepsis; Shock; Delayed diagnosis
17.  Diagnostic Accuracy of Point-of-Care Testing for Diabetic Ketoacidosis at Emergency-Department Triage 
Diabetes Care  2011;34(4):852-854.
In the emergency department, hyperglycemic patients are screened for diabetic ketoacidosis (DKA) via a urine dipstick. In this prospective study, we compared the test characteristics of point-of-care β-hydroxybutyrate (β-OHB) analysis with the urine dipstick.
Emergency-department patients with blood glucose ≥250 mg/dL had urine dipstick, chemistry panel, venous blood gas, and capillary β-OHB measurements. DKA was diagnosed according to American Diabetes Association criteria.
Of 516 hyperglycemic subjects, 54 had DKA. The urine dipstick had a sensitivity of 98.1% (95% CI 90.1–100), a specificity of 35.1% (30.7–39.6), a positive predictive value of 15% (11.5–19.2), and a negative predictive value of 99.4% (96.6–100) for DKA. Using the manufacturer-suggested cutoff of >1.5 mmol/L, β-OHB had a sensitivity of 98.1% (90.1–100), a specificity of 78.6% (74.5–82.2), a positive predictive value of 34.9% (27.3–43), and a negative predictive value of 99.7% (98.5–100) for DKA.
Point-of-care β-OHB and the urine dipstick are equally sensitive for detecting DKA (98.1%). However, β-OHB is more specific (78.6 vs. 35.1%), offering the potential to significantly reduce unnecessary DKA work-ups among hyperglycemic patients in the emergency department.
PMCID: PMC3064039  PMID: 21307381
18.  Predictive Value of Capnography for Suspected Diabetic Ketoacidosis in the Emergency Department 
Metabolic acidosis confirmed by arterial blood gas (ABG) analysis is one of the diagnostic criteria for diabetic ketoacidosis (DKA). Given the direct relationship between end-tidal carbon dioxide (ETCO2), arterial carbon dioxide (PaCO2), and metabolic acidosis, measuring ETCO2 may serve as a surrogate for ABG in the assessment of possible DKA. The current study focuses on the predictive value of capnography in diagnosing DKA in patients referring to the emergency department (ED) with increased blood sugar levels and probable diagnosis of DKA.
In a cross-sectional prospective descriptive-analytic study carried out in an ED, we studied 181 patients older than 18 years old with blood sugar levels of higher than 250 mg/dl and probable DKA. ABG and capnography were obtained from all patients. To determine predictive value, sensitivity, specificity and cut-off points, we developed receiver operating characteristic curves.
Sixty-two of 181 patients suffered from DKA. We observed significant differences between both groups (DKA and non-DKA) regarding age, pH, blood bicarbonate, PaCO2 and ETco2 values (p≤0.001). Finally, capnography values more than 24.5 mmHg could rule out the DKA diagnosis with a sensitivity and specificity of 0.90.
Capnography values greater than 24.5 mmHg accurately allow the exclusion of DKA in ED patients suspected of that diagnosis. Capnography levels lower that 24.5 mmHg were unable to differentiate between DKA and other disease entities.
PMCID: PMC3876300  PMID: 24381677
19.  Coronary Artery Bypass Grafting: A Precipitating Factor for Perioperative Diabetic Ketoacidosis 
Non-Insulin Dependent Diabetes Mellitus (NIDDM) is a common disease entity in patients with Coronary Artery Disease (CAD). Diabetic Ketoacidosis (DKA) is not only one of the major complications of Diabetes Mellitus but also a significant challenging clinical entity for the patients undergoing any elective or emergency surgery. Coronary Artery Bypass Grafting (CABG) being done in a patient with DKA has not been reported. We are presenting a rare case with DKA in whom CABG was carried out in a hospital devoted exclusively to cardiac cases. Insulin was given in very large doses as a part of therapeutic regimen and the outcome was favorable. This report concludes that if a patient undergoing urgent cardiac surgery incidentally develops DKA after induction of anesthesia, then the operation can be carried out provided DKA is managed aggressively. Also, major stress factors like cardio pulmonary bypass (CPB) and hypothermia should be avoided and care should be taken to avoid cerebral edema.
PMCID: PMC3693665  PMID: 23825985
Coronary Artery Bypass Grafting; Diabetes Mellitus; Diabetic Ketoacidosis; Insulin
20.  Acidosis: The Prime Determinant of Depressed Sensorium in Diabetic Ketoacidosis 
Diabetes Care  2010;33(8):1837-1839.
The etiology of altered sensorium in diabetic ketoacidosis (DKA) remains unclear. Therefore, we sought to determine the origin of depressed consciousness in DKA.
We analyzed retrospectively clinical and biochemical data of DKA patients admitted in a community teaching hospital.
We recorded 216 cases, 21% of which occurred in subjects with type 2 diabetes. Mean serum osmolality and pH were 304 ± 31.6 mOsm/kg and 7.14 ± 0.15, respectively. Acidosis emerged as the prime determinant of altered sensorium, but hyperosmolarity played a synergistic role in patients with severe acidosis to precipitate depressed sensorium (odds ratio 2.87). Combination of severe acidosis and hyperosmolarity predicted altered consciousness with 61% sensitivity and 87% specificity. Mortality occurred in 0.9% of the cases.
Acidosis was independently associated with altered sensorium, but hyperosmolarity and serum “ketone” levels were not. Combination of hyperosmolarity and acidosis predicted altered sensorium with good sensitivity and specificity.
PMCID: PMC2909073  PMID: 20484127
21.  Recurrent Diabetic Ketoacidosis in Inner-City Minority Patients 
Diabetes Care  2011;34(9):1891-1896.
To conduct a bedside study to determine the factors driving insulin noncompliance in inner-city patients with recurrent diabetic ketoacidosis (DKA).
We analyzed socioeconomic and psychological factors in 164 adult patients with DKA who were admitted to Grady Hospital between July 2007 and August 2010, including demographics, diabetes treatment, education, and mental illness. The Patient Health Questionnaire-9 and the Short Form-36 surveys were used to screen for depression and assess quality of life.
The average number of admissions was 4.5 ± 7 per patient. A total of 73 patients presented with first-time DKA, and 91 presented with recurrent DKA; 96% of patients were African American. Insulin discontinuation was the leading precipitating cause in 68% of patients; other causes were new-onset diabetes (10%), infection (15%), medical illness (4%), and undetermined causes (3%). Among those who stopped insulin, 32% gave no reasons for stopping, 27% reported lack of money to buy insulin, 19% felt sick, 15% were away from their supply, and 5% were stretching insulin. Compared with first-time DKA, those with recurrent episodes had longer duration of diabetes (P < 0.001), were a younger age at the onset of diabetes (P = 0.04), and had higher rates of depression (P = 0.04), alcohol (P = 0.047) and drug (P < 0.001) abuse, and homelessness (P = 0.005). There were no differences in quality-of-life scores, major psychiatric illnesses, or employment between groups.
Poor adherence to insulin therapy is the leading cause of recurrent DKA in inner-city patients. Several behavioral, socioeconomic, psychosocial, and educational factors contribute to poor compliance. The recognition of such factors and the institution of culturally appropriate interventions and education programs might reduce DKA recurrence in minority populations.
PMCID: PMC3161256  PMID: 21775761
22.  The risk and outcome of cerebral oedema developing during diabetic ketoacidosis 
BACKGROUND—Cerebral oedema is a major cause of morbidity and mortality in children with insulin dependent diabetes.
AIMS—To determine the risk and outcome of cerebral oedema complicating diabetic ketoacidosis (DKA).
METHODS—All cases of cerebral oedema in England, Scotland, and Wales were reported through the British Paediatric Surveillance Unit between October 1995 and September 1998. All episodes of DKA were reported by 225 paediatricians identified as involved in the care of children with diabetes through a separate reporting system between March 1996 and February 1998. Further information about presentation, management, and outcome was requested about the cases of cerebral oedema. The risk of cerebral oedema was investigated in relation to age, sex, seasonality, and whether diabetes was newly or previously diagnosed.
RESULTS—A total of 34 cases of cerebral oedema and 2940 episodes of DKA were identified. The calculated risk of developing cerebral oedema was 6.8 per 1000 episodes of DKA. This was higher in new (11.9 per 1000 episodes) as opposed to established (3.8 per 1000) diabetes. There was no sex or age difference. Cerebral oedema was associated with a significant mortality (24%) and morbidity (35% of survivors).
CONCLUSIONS—This first large population based study of cerebral oedema complicating DKA has produced risk estimates which are more reliable and less susceptible to bias than those from previous studies. Our study indicates that cerebral oedema remains an important complication of DKA during childhood and is associated with significant morbidity and mortality. Little is known of the aetiology of cerebral oedema in this condition and we are currently undertaking a case control study to address this issue.

PMCID: PMC1718828  PMID: 11420189
23.  Prevalence and significance of lactic acidosis in diabetic ketoacidosis☆ 
Journal of critical care  2011;27(2):132-137.
The prevalence and clinical significance of lactic acidosis in diabetic ketoacidosis (DKA) are understudied. The objective of this study was to determine the prevalence of lactic acidosis in DKA and its association with intensive care unit (ICU) length of stay (LOS) and mortality.
Retrospective, observational study of patients with DKA presenting to the emergency department of an urban tertiary care hospital between January 2004 and June 2008.
Sixty-eight patients with DKA who presented to the emergency department were included in the analysis. Of 68 patients, 46 (68%) had lactic acidosis (lactate, >2.5 mmol/L), and 27 (40%) of 68 had a high lactate (>4 mmol/L). The median lactate was 3.5 mmol/L (interquartile range, 3.32–4.12). There was no association between lactate and ICU LOS in a multivariable model controlling for Acute Physiology and Chronic Health Evaluation II, glucose, and creatinine. Lactate correlated negatively with blood pressure (r = −0.44; P < .001) and positively with glucose (r = 0.34; P = .004).
Lactic acidosis is more common in DKA than traditionally appreciated and is not associated with increased ICU LOS or mortality. The positive correlation of lactate with glucose raises the possibility that lactic acidosis in DKA may be due not only to hypoperfusion but also to altered glucose metabolism.
PMCID: PMC3610316  PMID: 22033060
Diabetic ketoacidosis; Lactic acidosis; Diabetes; Acidosis
24.  Age-Related Differences in the Frequency of Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents 
Diabetes Care  2010;33(7):1500-1502.
We studied the prevalence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in children in Finland.
From 2002 to 2005, data on virtually all children <15 years of age diagnosed with type 1 diabetes (n = 1,656) in Finland were collected.
DKA was present in 19.4% of the case subjects, and 4.3% had severe DKA. In children aged 0–4, 5–9, and 10–14 years, DKA was present in 16.5, 14.8, and 26.4%, respectively (P < 0.001). Severe DKA occurred in 3.7, 3.1, and 5.9%, respectively (P = 0.048). DKA was present in 30.1% and severe DKA in 7.8% of children aged <2 years.
The overall frequency of DKA in children is low in Finland at diagnosis of type 1 diabetes. However, both children <2 years of age and adolescents aged 10–14 years are at increased risk of DKA.
PMCID: PMC2890349  PMID: 20413519
25.  Diabetic Ketoacidosis at Diagnosis Influences Complete Remission After Treatment With Hematopoietic Stem Cell Transplantation in Adolescents With Type 1 Diabetes 
Diabetes Care  2012;35(7):1413-1419.
To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (AHSCT) was beneficial for type 1 diabetic adolescents with diabetic ketoacidosis (DKA) at diagnosis.
We enrolled 28 patients with type 1 diabetes, aged 14–30 years, in a prospective AHSCT phase II clinical trial. HSCs were harvested from the peripheral blood after pretreatment consisting of a combination of cyclophosphamide and antithymocyte globulin. Changes in the exogenous insulin requirement were observed and serum levels of HbA1c, C-peptide, and anti-glutamic acid decarboxylase antibody were measured before and after the AHSCT.
After transplantation, complete remission (CR), defined as insulin independence, was observed in 15 of 28 patients (53.6%) over a mean period of 19.3 months during a follow-up ranging from 4 to 42 months. The non-DKA patients achieved a greater CR rate than the DKA patients (70.6% in non-DKA vs. 27.3% in DKA, P = 0.051). In the non-DKA group, the levels of fasting C-peptide, peak value during oral glucose tolerance test (Cmax), and area under C-peptide release curve during oral glucose tolerance test were enhanced significantly 1 month after transplantation and remained high during the 24-month follow-up (all P < 0.05). In the DKA group, significant elevation of fasting C-peptide levels and Cmax levels was observed only at 18 and 6 months, respectively. There was no mortality.
We have performed AHSCT in 28 patients with type 1 diabetes. The data show AHSCT to be an effective long-term treatment for insulin dependence that achieved a greater efficacy in patients without DKA at diagnosis.
PMCID: PMC3379609  PMID: 22723579

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