Diabetic Ketoacidosis Group Research Articles

THE PLATELET-TO-LYMPHOCYTE RATIO ON ACUTE COMPLICATION OF DIABETES MELLITUS

Hariogie Putradi1, Catur Suci Sutrisnani21Resident of Clinical Pathology Department, Faculty of Medicine Brawijaya University Malang/ dr. Saiful Anwar General Hospital, Malang2Clinical Pathology Department, Faculty of Medicine Brawijaya University Malang/ dr. Saiful Anwar General Hospital, MalangABSTRACTBackgroundHyperglycemia crisis can occur in Diabetes Mellitus (DM). The uncontrolled complications of DM are Diabetic Ketoacidosis (DKA) and Hyperglycemic Hyperosmolar State (HHS). Inflammatory response is potentially occur in these condition. Platelet-to-Lymphocyte Ratio (PLR) is a new marker of inflammation in which platelet counts tend to increase, while lymphocyte counts tend to decrease due to severe apoptosis. AimDescribe PLR on acute complication of DM and to know the difference of PLR between DKA and non-DKA (HHS and Mixed).MethodRetrospective study in patients with acute complication of DM in dr. Saiful Anwar General Hospital Malang in January 2017-May 2018. The platelet and lymphocyte count were obtained from the Laboratory Information System (LIS). The PLR was calculated by dividing the platelet count by the lymphocyte count.ResultA total of 71 patients were involved in the study, consisting of 21 DKA patients and 50 non-DKA patients. There was significant difference of platelet count between DKA and non-DKA patients (p=0,001). However, there were no significant differences of lymphocyte count (p=0,087) and PLR (p=0,762) between DKA and non-DKA patients.DiscussionIn DKA, there is a chronic inflammatory process that can affect PLR. As a result, platelet counts tend to increase, while lymphocyte counts tend to decrease due to severe apoptosis. Conclusion and SuggestionThe study showed significant difference of platelet count between DKA and non-DKA groups, and no significant difference of PLR between DKA and non-DKA groups. It is recommended to conduct further research with larger sample size.

Impact of Early Diabetic Ketoacidosis on the Developing Brain.

OBJECTIVEThis study examined whether a history of diabetic ketoacidosis (DKA) is associated with changes in longitudinal cognitive and brain development in young children with type 1 diabetes.RESEARCH DESIGN AND METHODSCognitive and brain imaging data were analyzed from 144 children with type 1 diabetes, ages 4 to <10 years, who participated in an observational study of the Diabetes Research in Children Network (DirecNet). Participants were grouped according to history of DKA severity (none/mild or moderate/severe). Each participant had unsedated MRI scans and cognitive testing at baseline and 18 months.RESULTSIn 48 of 51 subjects, the DKA event occurred at the time of onset, at an average of 2.9 years before study entry. The moderate/severe DKA group gained more total and regional white and gray matter volume over the observed 18 months compared with the none/mild group. When matched by age at time of enrollment and average HbA1c during the 18-month interval, participants who had a history of moderate/severe DKA compared with none/mild DKA were observed to have significantly lower Full Scale Intelligence Quotient scores and cognitive performance on the Detectability and Commission subtests of the Conners’ Continuous Performance Test II and the Dot Locations subtest of the Children’s Memory Scale.CONCLUSIONSA single episode of moderate/severe DKA in young children at diagnosis is associated with lower cognitive scores and altered brain growth. Further studies are needed to assess whether earlier diagnosis of type 1 diabetes and prevention of DKA may reduce the long-term effect of ketoacidosis on the developing brain.

Diabetic ketoacidosis; Annual Incidence and Precipitating Factors at King Abdulaziz Medical city, Jeddah

Introduction: Diabetes is a recognizable and major health burden in Saudi Arabia. The incidence of Diabetes Mellitus Type 1 (DM1) reached 109.5 per 100,000 child and adolescent. One of the major life-threatening complications of DM1 is Diabetic Ketoacidosis (DKA). This study aims to estimate DKA incidence among DM1 patients and possible risk factors. Methods: Retrospective review for DM1 patients at King Abdul-Aziz Medical City, and who was presented with DKA during the past six and half years. Results: Three hundred and fifty DM1 patients were included and (72) experienced DKA during study period. The average annual DKA onset was (6.2%). Mean age was (22.82 ± 5.567) years, and females constituted (66.7%) of this group. Poor medication compliance was the commonest risk factor associated with DKA, and this relationship was found significant (P-value 0.003). Out of the total DKA sufferers, (28) patients experienced recurrent or multiple DKA episodes, and those had higher HbA1C levels (11.7 ± 2.9 Vs 12.4 ± 3.3). Patients who had multiple DKA episodes reported less visits to the diabetes educator when compared to the single DKA group. (On average (9) Vs (11) per year). Conclusion: DKA was found relatively uncommon among our DM1 patients, and usually seen in young females with poor medication compliance. More comprehensive education on DKA is needed to protect against life threatening complications.

Brain injury markers: S100 calcium-binding protein B, neuron-specific enolase and glial fibrillary acidic protein in children with diabetic ketoacidosis.

To investigate serum levels of brain injury markers in diabetic ketoacidosis (DKA) and the relation of these markers with clinical and radiological findings of brain injury and laboratory results. Twenty-nine patients with DKA, 30 with type 1 diabetes mellitus (T1DM), and 35 healthy children were included. Clinical and laboratory findings, and the Glasgow Coma Scale (GCS) were recorded. In the DKA group, neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B) and glial fibrillary acidic protein (GFAP) levels were measured at baseline and 6 and 12 hours after treatment. Magnetic resonance imaging was performed in the DKA group to demonstrate any brain injury. No clinical or radiological findings of brain injury were found in any of the patients with DKA. In the DKA group, S100B was significantly higher than the healthy control and T1DM groups, while GFAP and NSE levels were not different from controls and T1DM patients. No significant differences were found in GFAP, NSE and S100B levels according to severity of DKA, diabetes duration and GCS. NSE and GFAP levels do not increase in DKA patients without overt brain injury. Elevated levels of S100B, which is also synthesized from non-neuronal tissues, might arise from peripheral sources. A lack of concurrent increase in serum levels of these brain injury markers might result from the yet intact blood brain barrier or a true absence of neuronal damage. In order to reveal subclinical brain injury related to DKA, there is a need for studies concurrently assessing neurocognitive functions.

Concurrent Diabetic Ketoacidosis in Hypertriglyceridemia-Induced Pancreatitis: How Does It Affect the Clinical Course and Severity Scores?

Concurrent diabetic ketoacidosis (DKA) is highly prevalent in patients with hypertriglyceridemia-induced pancreatitis (HP). Diabetic ketoacidosis could potentially complicate the diagnosis, management, and prognosis of HP. This study aimed to directly compare the clinical course of HP with and without DKA and assess the outcomes of frequently used severity-prediction scores in such population. We retrospectively analyzed 140 patients with HP; 37 patients (26.4%) had concurrent DKA. We compared epidemiologic characteristics, initial laboratory values, and clinical courses between the DKA and non-DKA groups. Bedside Index for Severity in Acute Pancreatitis score, Sequential Organ Failure Assessment score, Ranson criteria, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Marshall score were calculated and compared between groups. We observed more acute kidney injury in the DKA group. Patients with DKA more likely required intensive care unit admission, received intravenous insulin, and were discharged on subcutaneous insulin. Ranson criteria and APACHE II score were significantly higher with DKA. Concurrent DKA does not affect length of stay, in-hospital mortality, and readmission rate in patients with HP. Higher Ranson criteria and APACHE II score likely reflected derangement of clinical parameters secondary to DKA rather than true severity of pancreatitis in such population.

Heart-Type Fatty Acid Binding Protein Level as a Tool in Identification of Early Cardiac Effects of Diabetic Ketoacidosis

Objective:This study aimed to measure the serum levels of heart-type fatty acid binding protein (H-FABP) in patients presenting with diabetic ketoacidosis (DKA) and diabetic ketosis (DK) and to determine its role in identifying early-period cardiac ischemia.Methods:This prospective study included 35 patients diagnosed with DKA, 20 patients diagnosed with DK, and 20 control subjects. H-FABP, creatine kinase-MB (CK-MB), and troponin I levels were investigated at presentation in patients with DKA and DK and in the control group. H-FABP values were measured again after acidosis correction in the DKA patients.Results:No statistically significant differences were found with respect to troponin I and CK-MB within the groups. The H-FABP values of DKA patients at presentation were found to be significantly higher than those of DK patients and the control group (p=0.015). The H-FABP value of the DKA group was also found to be significantly higher than the value at hour 36 after acidosis correction (p=0.0001).Conclusion:We would like to propose H-FABP as a potential marker for indicating myocardial ischemia.

Histological and cognitive alterations in adult diabetic rats following an episode of juvenile diabetic ketoacidosis: Evidence of permanent cerebral injury

Evidence suggests that diabetic ketoacidosis (DKA) may cause subtle cognitive alterations in children but the mechanisms are poorly understood. Acute DKA is associated with reactive astrogliosis and microglial activation in a rat model. Whether these inflammatory changes permanently alter brain histology is unknown. We aimed to determine whether DKA results in permanent alterations in brain histology and whether these changes are associated with cognitive deficits in a rat model. We induced diabetes in juvenile rats with streptozotocin at 4 weeks of age. We induced DKA in one group (n=21) at 5 weeks of age and compared this group to rats with diabetes without DKA episodes (n=13). Beginning at 7 weeks, rats underwent a series of cognitive tests to evaluate memory. At 15 weeks, rat brains were harvested and examined using immunohistochemistry (IHC). In tests of novel object recognition and social recognition, both groups performed similarly, however, the DKA group performed more poorly in object-place recognition tests, suggesting alterations in hippocampal function. IHC studies demonstrated increased glial fibrillary acidic protein staining intensity in the hippocampus of DKA rats suggesting astrogliosis, and decreased NeuN positive cell counts in the cortex suggesting neuron loss. These studies demonstrate that DKA results in permanent alterations in brain microstructure in a rat diabetes model. These structural changes are associated with deficits in hippocampal function.

Assessment of platelets morphological changes and serum butyrylcholinesterase activity in children with diabetic ketoacidosis: a case control study

BackgroundMany studies indicated that mean platelet volume (MPV) and platelet distribution width (PDW) may be valuable in the diagnosis and management of clinical disorders; also, serum butyrylcholinesterase activity (BChE) was suggested to be linked to systemic inflammation and oxidative stress. Limited studies measured these readily available markers in children with diabetic ketoacidosis (DKA). Our objectives were to measure MPV, PDW and BChE in children with DKA; and to assess if any of these markers reflects the severity of DKA.MethodsOur study included: 30 children with DKA (DKA group), 30 diabetic children (Non-DKA group) and 30 apparently healthy children (control group). MPV, PDW and BChE were measured in all children. Additional blood samples were withdrawn from the DKA group to assess these markers at discharge from hospital.ResultsMPV, PDW and BChE were significantly altered in the DKA group than the other two groups; and their levels improved significantly at discharge of the DKA group (p < 0.05). The three markers were found to equally to predict the presence of DKA, but MPV was the most suitable risk marker for DKA diagnosis (OR = 4.251, CI 95% =1.463–12.351, p = 0.003). Regarding their relation with DKA severity, they did not correlate significantly with arterial PH or serum HCO3- (p > 0.05).ConclusionDKA in children is associated with changes in MPV, PDW and BChE activity, which improve after resolution of the condition. Elevated MPV can be a suitable risk marker for DKA. None of the studied markers correlated with the severity of DKA.

An Evaluation of Recurrent Diabetic Ketoacidosis, Fragmentation of Care, and Mortality Across Chicago, Illinois.

A portion of patients with diabetes are repeatedly hospitalized for diabetic ketoacidosis (DKA), termed recurrent DKA, which is associated with poorer clinical outcomes. This study evaluated recurrent DKA, fragmentation of care, and mortality throughout six institutions in the Chicago area. A deidentified Health Insurance Portability and Accountability Act-compliant data set from six institutions (HealthLNK) was used to identify 3,615 patients with DKA (ICD-9 250.1x) from 2006 to 2012, representing 5,591 inpatient admissions for DKA. Demographic and clinical data were queried. Recurrence was defined as more than one DKA episode, and fragmentation of health care was defined as admission at more than one site. Of the 3,615 patients, 780 (21.6%) had recurrent DKA. Patients with four or more DKAs (n = 211) represented 5.8% of the total DKA group but accounted for 26.3% (n = 1,470) of the encounters. Of the 780 recurrent patients, 125 (16%) were hospitalized at more than one hospital. These patients were more likely to recur (odds ratio [OR] 2.96; 95% CI 1.99, 4.39; P < 0.0001) and had an average of 1.88-times the encounters than nonfragmented patients. Although only 13.6% of patients died of any cause during the study period, odds of death increased with age (OR 1.06; 95% CI 1.05, 1.07; P < 0.001) and number of DKA encounters (OR 1.28; 95% CI 1.04, 1.58; P = 0.02) after adjustment for age, sex, insurance, race, fragmentation, and DKA visit count. This study was limited by lack of medical record-level data, including comorbidities without ICD-9 codes. Recurrent DKA was common and associated with increased fragmentation of health care and increased mortality. Further research is needed on potential interventions in this unique population.

Acidosis-Induced Hypochloremic Alkalosis in Diabetic Ketoacidosis Confirmed by The Modified Base Excess Method.

Diabetic ketoacidosis (DKA) is associated with a metabolic alkalosis, which is thought to be due to vomiting. However, alkalosis can occur in DKA without vomiting. We retrospectively reviewed the acid-base disturbances in DKA admissions without vomiting. We included admissions of the patients with blood glucose and beta-hydroxybutyrate (βOHB) levels > 250 mg/dL and > 1.0 mmol/L, respectively. Admissions without vomiting were classified into a group with a βOHB > 3.0 mmol/L (DKA group) and a group with βOHB of 1.0-3.0 mmol/L (pre-DKA group). The acid-base status was analyzed by the modified base excess (BE) method. BE effects were calculated by changes in sodium (BE free water, [BEFW]), and chloride (BECl). Positive and negative values for each parameter suggested alkalosis and acidosis, respectively. Forty-five included admissions were divided into DKA (n = 34) and pre-DKA (n =11) groups. Sodium-corrected chloride level and the chloride/sodium ratio were significantly lower in the DKA group than in the pre-DKA group. In both groups, BEFW values were modestly negative. The mean BECl values were positive in both groups, but significantly higher in the DKA group. The alkalinizing effects by hypochloremia diminished the base deficit in the DKA group by approximately 25%. The BECl value significantly correlated with serum total ketone levels (r = 0.66; P < .0001). The modified BE method successfully proved the presence of hypochloremic alkalosis in DKA without vomiting. This suggests the direct participation of serum ketoacids in the pathogenesis of hypochloremic alkalosis.

Effects of Diabetic Ketoacidosis on Visual and Verbal Neurocognitive Function in Young Patients Presenting with New-Onset Type 1 Diabetes.

Objective:To evaluate the effects of diabetic ketoacidosis (DKA) on neurocognitive functions in children and adolescents presenting with new-onset type 1 diabetes.Methods:Newly diagnosed patients were divided into two groups: those with DKA and those without DKA (non-DKA). Following metabolic stabilization, the patients took a mini-mental status exam prior to undergoing a baseline battery of cognitive tests that evaluated visual and verbal cognitive tasks. Follow-up testing was performed 8-12 weeks after diagnosis. Patients completed an IQ test at follow-up.Results:There was no statistical difference between the DKA and non-DKA groups neither in alertness at baseline testing nor in an IQ test at follow-up. The DKA group had significantly lower baseline scores than the non-DKA group for the visual cognitive tasks of design recognition, design memory and the composite visual memory index (VMI). At follow-up, Design Recognition remained statistically lower in the DKA group, but the design memory and the VMI tasks returned to statistical parity between the two groups. No significant differences were found in verbal cognitive tasks at baseline or follow-up between the two groups. Direct correlations were present for the admission CO2 and the visual cognitive tasks of VMI, design memory and design recognition. Direct correlations were also present for admission pH and VMI, design memory and picture memory.Conclusion:Pediatric patients presenting with newly diagnosed type 1 diabetes and severe but uncomplicated DKA showed a definite trend for lower cognitive functioning when compared to the age-matched patients without DKA.

Diabetes and the blood – white cells and platelets

Diabetes and the blood – white cells and platelets

Analysis of influence factors of diabetic ketoacidosis in children with newly diagnosed type 1 diabetes mellitus

Objective To summarize the clinical features of diabetic ketoacidosis (DKA) in children with newly diagnosed type 1 diabetes mellitus(T1DM), and to explore the predictors of DKA by analyzing these factors in order to achieve early recognition. Methods In this retrospective study, 200 children with newly-onset T1DM from January 2009 to December 2012 in Shengjing Hospital of China Medical University were chosen.These patients were divided into DKA group and non-DKA group.Clinical data including age, gender, health insurance, body shape, infection history, family history of diabetes, type of residence, income, duration of history, C peptide, glycosylated hemoglobin, blood lipids, thyroid tests, diabetes antibodies etc were collected. Results Among 200 cases of newly diagnosed T1DM, 107 children had DKA, 93 children had non-DKA, and the incidence of DKA was 53.5%.In the group of DKA, 39 cases (36.5%) were male, 68 cases were female, while in the group of non-DKA 45 cases (48.4%) were male, 48 cases were female.In the group of DKA, children ranged in age from 16 months to 13 years old, and the average age was (6.53±3.55) years old.In the non-DKA group, children ranged in age from 1 to 14 years old, and the average age was (7.05±3.55)years old.In the group of DKA, 43 cases (40.2%) didn't have health insurance, while in the non-DKA group, 28 cases (30.1%) didn't have medical insurance.In the DKA group, 30 cases (28%) had a family history of diabetes, while in the non-DKA group, 27 cases (29%) had a family history of diabetes.In the group of DKA, the duration was (30.24±76.50 )days, while in the group of non-DKA, the duration was (33.38±49.30) days.The glycosylated hemoglobin in the DKA group was (12.38±2.66)%, in the non-DKA group was (12.48±2.24)%.There were no significantly differences of the above factors between the 2 groups(all P>0.05). In the group of DKA, 35 cases(32.7%) were thin, 66 cases(61.7%) were of normal size, and 6 cases(5.6%) were fat.In the group of non-DKA, 9 cases(9.3%) were thin, 76 cases (78.6%) were of normal size, and 8 cases(12.1%) were fat.In the group of DKA, 33 cases(30.8%) had infection history, 77 cases(72%) lived in rural areas, and the average of C peptide was (0.25±0.22) μg/L.In the group of non-DKA, 17 cases(18.3%) had infection history, 52 cases(55.9%) in rural areas, and the average of C peptide was (0.36±0.21) μg/L.There were significant differences of the above factors between the 2 groups(all P<0.05). Conclusions Children with newly diagnosed T1DM who is thin, rural resident, and has lower C peptide level is more susceptible to DKA.More attention should be paid to the children with newly diagnosed T1DM who have above characteristics. Key words: Type 1 diabetes mellitus; Diabetic ketoacidosis; Affect factor; Child

Retrospective evaluation of risk factors and outcome predictors in cats with diabetic ketoacidosis (1997-2007): 93 cases.

To determine risk factors and outcome predictors in cats with diabetic ketoacidosis (DKA). Retrospective study. Inclusion in the DKA group required blood glucose concentration > 13.9 mmol/L (250 mg/dL), venous pH < 7.35, and urine or serum acetoacetate concentration greater than 1.5 mmol/L (15 mg/dL). Signalment and weight were recorded in all cats with uncomplicated diabetes mellitus (DM) without DKA and in all other nondiabetic cats examined during the study period. Clinicopathologic variables, concurrent disorders, and initial insulin intravenous (IV) continuous-rate infusion (CRI) concentration of 1.1 or 2.2 U/kg/240 mL bag of 0.9% NaCl, were examined for a possible association with outcome. University teaching hospital. Ninety-three cats with DKA, 682 cats with uncomplicated DM, and 16,926 cats without DM or DKA. None. Cats with DKA were younger (median age 9.4 years; range, 1-17.9 years) than cats with uncomplicated DM (median 11.6 years; range 0.7-19.5 years, P < 0.0003). Siamese cats were overrepresented in the DKA group compared to the uncomplicated DM or nondiabetic group (P = 0.038 and P = 0.01, respectively). Poor outcome (defined as death due to disease or by euthanasia) in 36 cats with DKA (39%) was associated with increased initial creatinine, BUN, total serum magnesium, and total bilirubin concentrations (P = 0.007, P = 0.005, P = 0.03, P = 0.03, respectively). Cats treated with a higher concentration of insulin were less likely to have a poor outcome compared to cats treated with a lower concentration of insulin (odds ratio 0.14, 95% confidence interval 0.02-1.16, P = 0.02). Cats with DKA are more likely to be Siamese than cats with uncomplicated DM. Poor outcome of cats with DKA is associated with increased initial creatinine, BUN, total magnesium, and total bilirubin concentrations. Good outcome was associated with a higher concentration of IV insulin CRI.

Should diabetic ketosis without acidosis be included in ketosis‐prone type 2 diabetes mellitus?

The incidence of ketosis-prone type 2 diabetes is very low except for people of sub-Saharan African origin and African Americans. However, there also are some type 2 diabetes patients with diabetic ketosis without acidosis (DKWA). We question whether DKWA should be included as a subtype of ketosis-prone type 2 diabetes mellitus and compared the clinical characteristics of DKWA and diabetic ketoacidosis (DKA) patients. The study population consisted of 594 consecutive unrelated Chinese inpatients with newly diagnosed type 2 diabetes. Demographic and clinical characteristics (age, gender, family history of diabetes, body mass index, blood pressure and plasma lipid parameters) were recorded. The patients were divided into ketosis-resistant diabetes (KRD), DKWA and DKA groups on the basis of urinary ketones, blood pH and bicarbonate levels. The blood glucose and c-peptide levels of the patients were also evaluated. The prevalence of KRD, DKWA and DKA were 78.33%, 19.72% and 1.95%, respectively, in the study population. The clinical characteristics of patients with DKWA group patients were similar to those with DKA, except that DKA patients had higher blood glucose and deteriorated β cell function. Diabetic ketosis without acidosis and DKA patients share similar clinical characteristics; DKWA should be considered ketosis-prone type 2 diabetes. Therefore, the prevalence of ketosis-prone type 2 diabetes might be underestimated.

Characteristics of children presenting with newly diagnosed type 1 diabetes

Background. The clinical presentation of type 1 diabetes in children can be acute or insidious, and symptoms may be subtle and frequently misinterpreted. Presentation with diabetic keto-acidosis (DKA) may be associated with significant morbidity and mortality in the paediatric population. This study set out to determine the characteristics of children presenting to the paediatric endocrine service at Inkosi Albert Luthuli Central Hospital (IALCH) with DKA at the time of diagnosis, and to determine the frequency of missed diagnoses in the previous month. Methods. A retrospective study was done at IALCH, the paediatric tertiary referral centre for KwaZulu-Natal, South Africa. The study sample included all children with an initial diagnosis of type 1 diabetes between January 2008 and June 2010. Children presenting with DKA were compared with those who presented without DKA. Results. During the period under review, 63 children presented with type 1 diabetes. Of these, 44 (69.8%) had DKA at the time of diagnosis. The median duration of symptoms preceding diagnosis in the DKA group was 2 weeks, versus 4 weeks in the non-DKA group ( p =0.002). There was no significant difference between the groups when ethnicity, gender and age at presentation were compared. Of 42 patients who presented to healthcare facilities in the month preceding diagnosis, 27 (64.3%) were misdiagnosed. Conclusion. Patients who presented with DKA had a shorter duration of symptoms than the non-DKA group. Ethnicity had no effect on characteristics at presentation. There was an unacceptable rate of missed diagnoses of type 1 diabetes in both the private and public sectors.

Coagulation Assessment in Children With Diabetic Ketoacidosis*

To assess potential hypercoagulability during diabetic ketoacidosis in children. A prospective, controlled pilot study. University-affiliated pediatric critical care unit and emergency department in a tertiary care children's hospital. Children (1-18 years) admitted with an episode of diabetic ketoacidosis and healthy children as controls. All patients with diabetic ketoacidosis managed according to a preestablished protocol. Thromboelastography was performed using citrated whole-blood samples drawn at the time of admission and upon biochemical and clinical resolution of diabetic ketoacidosis. Citrated whole-blood samples drawn from healthy nondiabetic children acted as control samples. Fifteen patients (11.7 ± 4.1 years) in the diabetic ketoacidosis group and 20 patients (8.9 ± 4.5 years; p = 0.06) in the control group completed the study. Values for standard thromboelastography parameters (R and K time, α angle, maximum amplitude, coagulation index, and Ly30) in the diabetic ketoacidosis group, both on admission and resolution, were within the control range; thromboelastography profiles of diabetic ketoacidosis patients on admission were not significantly different from profiles obtained upon diabetic ketoacidosis resolution. The mean α-angle was significantly higher in known diabetic patients compared with newly diagnosed diabetics on admission; however, it still remained within the control normal range. Thromboelastographic assay results do not reflect a hypercoagulable state in this group of children with diabetic ketoacidosis. Further investigation is required to examine the potential role of injured endothelium in the suspected hypercoagulability during diabetic ketoacidosis.

Diabetic Ketoacidosis at Diagnosis Influences Complete Remission After Treatment With Hematopoietic Stem Cell Transplantation in Adolescents With Type 1 Diabetes

OBJECTIVETo determine if autologous nonmyeloablative hematopoietic stem cell transplantation (AHSCT) was beneficial for type 1 diabetic adolescents with diabetic ketoacidosis (DKA) at diagnosis.RESEARCH DESIGN AND METHODSWe 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.RESULTSAfter 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.CONCLUSIONSWe 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.

Cognitive dysfunction associated with diabetic ketoacidosis in rats

BackgroundType 1 diabetes mellitus in children may be associated with neurocognitive deficits of unclear cause. A recent retrospective study in children suggested possible associations between diabetic ketoacidosis (DKA) and decreased memory. The current investigation was undertaken to determine whether cognitive deficits could be detected after a single episode of DKA in an animal model. MethodsStreptozotocin was used to induce diabetes in juvenile rats, and rats were then treated with subcutaneous insulin injections. In one group, insulin was subsequently withdrawn to allow development of DKA, which was then treated with insulin and saline. After recovery from DKA, subcutaneous insulin injections were re-started. In the diabetes control group, rats continued to receive subcutaneous insulin and underwent sham procedures identical to the DKA group. One week after recovery, cognitive function was tested using the Morris Water Maze, a procedure that requires rats to locate a hidden platform in a water pool using visual cues. During a 10 day period, mean time to locate the platform (latency) during 4 trials per day was recorded. ResultsComparison of latency curves demonstrated longer mean latency times on days 7 and 8 in the DKA group indicating delayed learning compared to diabetic controls. ConclusionsThese data demonstrate that a single DKA episode results in measurable deficits in learning in rats, consistent with findings that DKA may contribute to neurocognitive deficits in children with type 1 diabetes.

Glycemic Control in Youth with Type 2 Diabetes Declines as Early as Two Years after Diagnosis

To determine the course of glycemic decline in a pediatric cohort with type 2 diabetes mellitus (T2DM) by defining longitudinal changes in hemoglobin A1c (HbA1c) and insulin requirement. We also followed markers of insulin reserve (fasting C-peptide and IGFBP-1) over time. Participants included two groups: (1) T2DM Nonacidotic (NA) (n = 46); and (2) T2DM diabetic ketoacidosis (n = 13). HbA1c, insulin dose, and fasting C-peptide and IGFBP-1 were obtained at baseline and every 6 months for 4 years. At baseline, Mann Whitney tests demonstrated that the diabetic ketoacidosis group had higher HbA1c (P = .002), required more insulin (P = .036), and had lower C-peptide (P = .003) than the NA group. Baseline insulin dose (Spearman r = -0.424, P = .009) and baseline IGFBP-1 (Spearman r = -0.349, P = .046) correlated negatively with C-peptide. Over time, HbA1c, insulin dose, and C-peptide changed significantly in a complex manner, with group differences. HbA1c reached a nadir at 6 to 12 months and began to rise after 1.5 years. Insulin requirements reached a nadir at 1 year and began to rise after 2 years. Unlike adults, children with T2DM require increasing insulin doses over a 4-year period, and diabetic ketoacidosis at diagnosis predicts greater β-cell decline over time.