Recurrent Diabetic Ketoacidosis in Two Community Teaching Hospitals

ObjectiveTo identify the factors that influence recurrent (one or more previous episodes) diabetic ketoacidosis (DKA), which we refer to as recurrent DKA, in two private community teaching hospitals.MethodsRetrospective chart review of the demographics, diabetes treatment regimens, diabetes education, medical comorbidities, medical insurance status, and mental illness/psychosocial factors of 80 patients with recurrent DKA who were admitted to the resident teaching services at two Birmingham, Alabama community teaching hospitals, Trinity Medical Center (TMC) and Princeton Baptist Medical Center (PBMC), between May 2006 and May 2012.ResultsThe average number of admissions for recurrent DKA was 2.5 per patient. Eighty-four percent of the episodes of recurrent DKA were due to omission of insulin; 44% of patients reported omission of insulin because of illness and 40% stopped insulin for unknown reasons. Medical illnesses, including infection, accounted for only 31% of recurrent DKA admissions.ConclusionOmission of insulin is the major cause of recurrent DKA. Psychosocial and socioeconomic factors contribute to poor adherence to therapy. Identifying these factors and instituting appropriate interventions may reduce the incidence of recurrent DKA. (Endocr Pract. 2013;19:829-833)     

Active use of Cocaine: An Independent Risk Factor for Recurrent Diabetic Ketoacidosis in a City Hospital

ObjectiveTo identify the risk factors for recurrent diabetic ketoacidosis (DKA) in a city hospital.MethodsWe performed a retrospective analysis of sequential adult admissions for DKA at Bronx Lebanon Hospital Center in New York between July 1, 2001, and June 30, 2004. The patients were divided into cohorts, which were compared with use of analysis of variance and χ² tests. Multivariate logistic regression analysis was performed where indicated.ResultsIn 168 patients (96 men and 72 women), 219 episodes of DKA occurred. The mean age (± SD) of the overall study group was 38.6 ± 14.8 years. Fifty-four patients (32%) had type 2 diabetes, and 44 patients (26%) had new-onset diabetes. The recurrence rate of DKA was 169% in cocaine users and 39% in nonusers (P < 0.0001). Active use of cocaine, noncompliance, and Hispanic ethnicity emerged as independent risk factors for recurrent DKA—odds ratio (OR) = 4.38, P = 0.001; OR = 1.96, P = 0.05; and OR = 0.40, P = 0.005, respectively. The commonest precipitants of DKA were noncompliance (44%) and infection (26%). Noncompliance was associated with use of cocaine, use of cannabis, and cigarette smoking (P = 0.008, 0.04, and 0.01, respectively). In 91 of the hospital admissions for DKA (42%), the patients were active smokers.ConclusionActive use of cocaine is an independent risk factor for recurrent DKA, as are noncompliance and Hispanic ethnicity. Of these 3 factors, cocaine showed the strongest association with DKA. Therefore, toxicology screening in patients with recurrent DKA may be prudent and worthwhile. (Endocr Pract. 2007;13:22-29)     

Family History of Diabetes is Associated with Increased Risk of Recurrent Diabetic Ketoacidosis in Pediatric Patients

Objective: To determine the relationship between family history of diabetes mellitus (DM) and diabetic ketoacidosis (DKA) recurrence in youth with established type 1 diabetes mellitus (T1DM).Methods: We performed a retrospective chart review of patients with DKA admitted to a pediatric hospital between January, 2009, and December, 2014. We compared patients with recurrent (≥2 admissions) and nonrecurrent DKA (1 admission) and investigated patient level factors, including family history, that may be associated with DKA recurrence in pediatric patients with established T1DM.Results: Of the 131 subjects in the study, 51 (39%) subjects were in the recurrence group. Age ≥15 years old, public health insurance, and family history of T1DM or type 2 diabetes mellitus were associated with recurrent DKA admissions in both univariable and multivariable analyses. Family history was associated with DKA recurrence, with an incidence rate ratio of 1.5 (95% confidence interval = 1.0 to 2.3; P = .03). The association was not explained by type of familial diabetes, first degree relative status, or whether the family member lived in the household.Conclusion: Recognition that a positive family history of DM may be associated with a higher risk for DKA recurrence in patients with established T1DM may allow for targeted education and focus on a previously unidentified population at increased risk for DKA. Understanding the mechanism underlying the effect of family history of diabetes on the rates of DKA in patients with established T1DM may allow for improved identification and education of patients who may be at risk for DKA recurrence.Abbreviations: CI = confidence interval; DKA = diabetic ketoacidosis; EHR = electronic health record; IBD = inflammatory bowel disease; IRR = incidence rate ratio; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus     

糖尿病酮症酸中毒合并吉兰-巴雷综合征2 例临床分析

目的:研究糖尿病酮症酸中毒(diabetic ketoacidosis,DKA)合并吉兰-巴雷综合征(Guillain-Barrésyndrome,GBS)的临床特点,以探讨其临床表现、治疗、预后及发病机制。方法:回顾性分析2例DKA合并GBS患者的病例资料,对其病史、临床表现、电生理学、脑脊液改变、治疗进行总结。结果:2例DKA患者均急性起病,两例患者发病前1周均有呼吸道感染史,尽管DKA得到了纠正,患者出现呼吸衰竭后被发现四肢力弱。肌电图提示周围神经损害。脑脊液示细胞蛋白分离。给予免疫球蛋白后,例1在出现肢体瘫痪后18天恢复至正常,遗留有四肢末端麻木感,例2在出现肢体瘫痪后1年肌力恢复正常。结论:DKA合并GBS临床少见,多发生在DKA纠正后一周左右出现四肢迟缓性瘫痪,早期给予免疫球蛋白治疗,预后相对良好,目前发病机制尚不清楚。     

Diabetic Ketoacidosis in Peruvian Patients with Type 2 Diabetes Mellitus

ObjectiveTo describe the clinical and laboratory characteristics of diabetic ketoacidosis (DKA) in adult Peruvian patients with type 2 diabetes mellitus.MethodsIn this cross-sectional analysis, we reviewed clinical charts of type 2 diabetic patients with DKA admitted to Cayetano Heredia Hospital between 2001 and 2005 for data on demographics, previous treatment, previous hospital admissions for DKA, family history of diabetes, precipitating factors, hospital course, mortality, and insulin use 3 and 6 months after the index DKA episode. Patients older than 18 years who had confirmed DKA were included. Patients with type 1 diabetes mellitus were excluded.ResultsWe report on 53 patients with DKA for whom complete clinical and laboratory data were available. Of the 53 patients, 39 (74%) were men; mean age (± SD) was 45 ± 12 years; and 22 (42%) had no previous diagnosis of type 2 diabetes. The following mean (± SD) laboratory values were obtained at DKA diagnosis: glucose, 457 ± 170 mg/dL; pH, 7.15 ± 0.14; bicarbonate, 7.73 ± 6 mEq/L; and anion gap, 24.45 ± 7.44 mEq/L. Of the 53 DKA episodes, 35 (66%) were severe (arterial pH < 7.0 and/or serum bicarbonate < 10 mEq/L). The following precipitating factors were discerned: discontinuation of treatment in 21 (40%), infections in 16 (30%), intercurrent illness in 3 (6%), and no identifiable cause in 13 (25%). Mortality rate was 0%. Three and 6 months after the index DKA episode, insulin was used by 65% and 56% of patients, respectively.ConclusionIn countries with a low incidence of type 1 diabetes, DKA is frequently reported in patients with type 2 diabetes. In this study, 42% of patients had new-onset disease. Most DKA episodes were severe and were related to infection or noncompliance with treatment. (Endocr Pract. 2008;14:442-446)     

Muscle glutamine production in diabetic ketoacidotic rats.

The mechanism of activation of glutamine production by the hindlimb during diabetic ketoacidosis (DKA) was investigated in rats. Muscle glutamine production was estimated to account for over 90% of the total glutamine produced by the hindlimb. DKA produced significant increases in the concentrations of NH4+ and IMP in hindlimb muscles, suggesting that AMP deaminase is activated by DKA. NH4Cl- and HCl-induced acidosis did not produce these changes, indicating either that acidosis itself is not the stimulus for increased AMP deaminase activity or that the more severe degree of acidosis accompanying DKA is necessary for activation. Muscle glutamine concentrations were depressed in DKA. Experiments with isolated epitrochlearis muscle showed that the transport and permeability properties of the muscle cells (as judged by uptake and release of alpha-aminoisobutyrate and glutamine) were not altered by DKA. However, glutamine uptake by muscle cells was significantly inhibited by L-leucine, the concentration of which, along with other branched-chain amino acids, is markedly elevated in DKA.     

Development of the Antiviral State in Response to Interferon

The development of resistance in response to interferon depends on cellular RNA synthesis and probably also on cellular protein synthesis. The evidence for these requirements is reviewed, as well as the proposal that this evidence indicates the existence of a specific response of the cell to interferon, involving the induced synthesis of an antiviral protein. Direct evidence for such an interpretation has not been obtained, and alternative explanations are discussed which do not require quantitative or qualitative differences in the RNA and protein made in cells exposed to interferon. The possible role of the ribosome in the antiviral action of interferon is also discussed.     

Dissecting Tn5 transposition using HIV-1 integrase diketoacid inhibitors

Diketoacid (DKA) compounds have been shown to inhibit HIV-1 integrase by a mechanism that involves sequestration of the active site metals. Because HIV-1 integrase and Tn5 transposase have similar active site architectures and catalytic mechanisms, we investigated whether DKA analogues would inhibit Tn5 transposase activity and provide a model system to explore the mechanisms of action of these inhibitors. A screen of several hundred DKA analogues identified several with activity against Tn5 Tnp. Six DKA inhibitors used in this study manifested a variety of effects on different transposition steps suggesting that different analogues may have different binding contacts with transposase. All DKA compounds inhibited paired end complex (PEC) formation in which the nucleoprotein complex required for catalysis is assembled. Dissociation of PECs by some DKA compounds indicates that these inhibitors can decrease PEC stability. Four DKA compounds inhibited the two cleavage steps releasing transposon DNA from flanking DNA, and one of these four compounds preferentially inhibited the second cleavage step. The differential effect of this inhibitor on the second cleavage event indicates that cleavage of the two transposon-donor DNA boundaries is a sequential process requiring a conformational change. The requirement for a conformational change between cleavage events was also demonstrated by the inability of transposase to perform second cleavage at 25 degrees C. Finally, all six compounds inhibit strand transfer, the final step of Tn5 transposition. Two of the compounds that inhibited strand transfer have no effect on DNA cleavage. The strand transfer inhibition properties of various DKA compounds was sensitive to the structure of the 5'-non-transferred strand, suggesting that these compounds bind in or near the transposase active site. Other results that probe compound binding sites include the effects of active site mutations and donor DNA on DKA compound inhibition activities. Thus, DKA inhibitors will provide an important set of tools to investigate the mechanism of action of transposases and integrases.     

Efficacy of empirical cardiac pacing in syncope of unknown cause.

Cardiac pacing is often considered in patients with recurrent syncope after repeated attempts to document the cause have failed. To assess the results of this tactic we reviewed the records of 104 patients who had received pacemakers for known or suspected bradycardia between September 1973 and March 1985. The patients were classified retrospectively into three groups: group 1 (31 patients with a mean age of 73 years) had unequivocal documentation of bradycardia during syncope, group 2 (42 patients with a mean age of 71 years) had electrocardiographic or electrophysiologic evidence of potential bradycardia but no documentation during spontaneous syncope, and group 3 (31 patients with a mean age of 69 years) had a history "suggestive of" bradycardia-related syncope but no other evidence to support the diagnosis. The rates of recurrence of syncope during follow-up were 6.3%, 7.3% and 32.2% in groups 1, 2 and 3 respectively (p less than 0.01). In group 3 recurrence was more probable in patients with loss of consciousness for more than 2 minutes than in those who were unconscious for 2 minutes or less (p less than 0.05). The results suggest that pacemaker implantation is justified for recurrent syncope after extensive attempts to document a spell have failed if abnormal diagnostic test results suggest bradycardia as a possible cause. Empirical pacing is less satisfactory in patients with normal results of evaluation but may arguably be justified when patients have recurrent syncope with injury.     

Hypothalamopituitary deficiency and precocious puberty following hyperhydration in diabetic ketoacidosis.

We report on a 5-year-old child who survived an intracerebral crisis, following ketoacidosis-revealing diabetes (DKA), with visual impairment due to a vascular occipital lesion. Two and 4 months after the initial episode, a unique hypothalamopituitary disorder consisting in GH, ACTH, TSH deficiencies and central precocious puberty, was detected. Cranial magnetic resonance images showed no visible lesion in the hypothalamopituitary region. The most likely hypothesis is the ischemia of hypothalamopituitary and occipital regions following possible cerebral edema after hyperhydration. She survived with low visual acuteness and received a combined replacement therapy for the neuroendocrinological deficiencies. This case emphasizes that the rehydration at the initial period of DKA is critical, especially when risk factors for cerebral edema are present (young age, marked hyponatremia). The neuroendocrinological consequences of acute cerebral edema are rare, but physicians must be attentive in survivors of these accidents.     

Nuclear and cytoskeletal translocation and localization of heterotrimeric G-proteins

Heterotrimeric GTP-binding proteins (G-proteins) are involved in a diverse array of signalling pathways. They are generally thought to be membrane-bound proteins, which disassociate on receptor activation and binding of GTP. A model to explain this has been proposed, which is often described as 'the G-protein cycle'. The 'G-protein cycle' is discussed in the present paper in relation to evidence that now exists regarding the non- membranous localization of G-proteins. Specifically, the experimental evidence demonstrating association of G-proteins with the cytoskeleton and the nucleus, and the mechanisms by which G-proteins translocate to these sites are reviewed. Furthermore, the possible effector pathways and the physiological function of G-proteins at these sites are discussed.     

Causes and Predictors for 30-DAY Re-Admissions in Adult Patients with Diabetic Ketoacidosis in the United States: a Nationwide Analysis, 2010–2014

Objective: We aimed to determine the causes and predictors for 30-day re-admission following a hospitalization for diabetic ketoacidosis (DKA) in the United States.Methods: This retrospective cohort study analyzed data from the National Re-admission Database. We included adult patients with a primary discharge diagnosis of DKA, from 2010 to 2014. Our primary objective was to determine the frequency and causes for 30-day re-admission after an index hospitalization for DKA. We also performed multivariate regression analyses using covariates from the index admission to identify predictors for 30-day re-admissions.Results: Among 479,590 admissions for DKA, 58,961 (12.3%) were re-admitted within 30 days. Recurrent DKA represented 40.8% of all-cause re-admissions. In multivariate analysis, end-stage renal disease (odds ratio &lsqb;OR], 2.13; 95% confidence interval &lsqb;CI], 2.00 to 2.27; P<.001), Charlson Comorbidity Index ≥3 (OR, 2.49; 95% CI, 2.42 to 2.58; P<.001), discharge against medical advice (OR, 1.97; 95% CI, 1.86 to 2.09; P<.001), and drug use (OR, 1.78; 95% CI, 1.71 to 1.86; P<.001) were the most significant predictors for 30-day re-admission. About 50% of patients were re-admitted within 2 weeks after discharge.Conclusion: In the U.S., about one in every eight patients with DKA is re-admitted within 30 days, with 40.8% representing recurrent DKA episodes. Patients with end-stage renal disease, high comorbidity burden, drug use, and/or leaving against medical advice represented the highest risk group for re-admissions. Future studies with interventions focusing on high-risk population are critically needed.Abbreviations: AKI = acute kidney injury; BMI = body mass index; CCI = Charlson Comorbidity Index; CI = confidence interval; DKA = diabetic ketoacidosis; DM1 = type 1 diabetes mellitus; DM2 = type 2 diabetes mellitus; ESRD = end-stage renal disease; ICD-9-CM = International Classification of Diseases, Ninth Edition, Clinical Modification; IQR = interquartile range; LOS = length of stay; NRD = National Re-admission Database; OR = odds ratio     

Conditional control transfer mechanisms in the neocortex: 2. Cytoarchitectural and electrophysiological evidence and predictions.

Neuroanatomical and electrophysiological evidence appertaining to the model of the neocortex described in the preceding paper is discussed. It is shown that pyramid cells appear to have the properties of the proposed M type cells. There is a considerable body of evidence suggesting that neocortical basket cells are the interneurones which transmit recurrent inhibition from collateral axons of pyramid cells. Hence it is possible to identify the proposed C type cells as basket cells. The pathways transmitting context information from outside the cortex are identified with specific thalamic afferents which terminate on spiny stellate cells in lamina IV which in turn appear to form powerful excitatory synaptic contacts on pyramid cells. The pathways transmitting context information short distances within the cortex are identified with the excitatory recurrent collateral axons of pyramid cells. It is suggested that transmission of context information over longer distances within the cortex is mediated by pyramid cells whose axons project to other cortical areas and terminate in laminae II and III. It is tentatively suggested that these terminals may be on “cellules a double bouquet dendritique” which appear to have strong excitatory projections to neighbouring pyramid cells.A number of neuroanatomical predictions are discussed.     

Inpatient Perioperative Euglycemic Diabetic Ketoacidosis Due to Sodium-Glucose Cotransporter-2 Inhibitors – Lessons From a Case Series and Strategies to Decrease Incidence

ObjectiveTo identify clinical characteristics and factors associated with the development of euglycemic diabetic ketoacidosis (eDKA), and develop suitable strategies to reduce such events.MethodsElectronic health record (EHR) data were extracted to identify all patients between December 1, 2013, and March 30, 2021, who underwent surgical procedures and had been prescribed a sodium-glucose cotransporter 2 inhibitor (SGLT2i) before these procedures. The resulting list was streamlined to a subset of patients who either had diabetic ketoacidosis (DKA) listed as a hospital diagnosis, postoperative serum bicarbonate ≤ 16 mmol/L, or postoperative serum pH ≤ 7.20. Clinical documentation and laboratory data were reviewed to determine the patients with eDKA.ResultsA total of 2183 procedures conducted on 1307 patients, met the inclusion criteria with the majority (1726, 79.1%) being nonemergent patients. Among 1307 patients, 625 (47.8%) were prescribed empagliflozin, 447 (34.2%) canagliflozin, 214 (16.4%) dapagliflozin, and 21 (1.6%) ertugliflozin, respectively. A total of 8 incidences pertaining to eDKA were noted for 8 unique patients; 5 had undergone emergency surgery whereas 3 had undergone nonemergent procedures. In the 3 nonemergent cases, only 1 patient had received counseling to stop the SGLT2i 3 days before the procedure. In perioperative patients who were prescribed an SGLT2i over 6 years, the incidence of eDKA was 0.17% and 1.1% for nonemergent and emergent procedures, respectively.ConclusionEuglycemic DKA was rare in patients undergoing nonemergent procedures, likely because of preoperative instructions to stop their SGLT2i 3 days before the procedure. Euglycemic DKA was more likely to occur in patients undergoing emergency surgery when the SGLT2i could not be prophylactically stopped.     

Diabetic ketoacidosis induces in vivo activation of human T-lymphocytes

Diabetic ketoacidosis (DKA) is an inflammatory state associated with immune responses in polymorphonuclear cells (PMN). Activation of subgroup of T-lymphocytes in PMN of DKA patients, however, is not known. We studied in vivo activation of CD4 and CD8 lymphocytes by measuring de novo growth factor receptor for insulin, IGF-1, and IL-2 in eight patients on admission and at resolution of DKA, and compared them with matched controls. The presence of these receptors was demonstrated in all patients' lymphocytes on admission, but not in control subjects. This event was associated with increased levels of thiobarbituric acid-reacting material and dichlorofluorescien, as markers of oxidative stress. Based on these new findings and works in the literature, we hypothesize that hyperglycemia/ketosis results in increased reactive oxygen species, leading to increased levels of cytokines and emergence of growth factor receptors. We propose DKA changes the T-lymphocytes to insulin sensitive tissues as a compensatory mechanism.     

Membrane Fusion Induced by Phospholipase C and Sphingomyelinases

In the past decade lipid vesicle fusion induced by either bacterial PC-preferring phospholipase C, phosphatidylinositol-specific phospholipase C, sphingomyelinase, or a combination of phospholipase C and sphingomyelinase has been demonstrated. In the present paper, the experimental evidence is reviewed, and discussed in terms of the underlying molecular mechanisms of fusion, and of the possible physiological relevance of these findings.     

Non-secretion of ABO blood group antigens: a host factor predisposing to recurrent urinary tract infections and renal scarring

In a study of 718 women referred for specialist investigation for recurrent urinary tract infections, 250 (34.8%, P less than 0.01) were non-secretors. The proportion of non-secretors among the women with renal scars (42.6%) was higher than that found for women with no evidence of renal scars (36.6%). Among 29 patients in whom symptoms began in childhood or adolescence, 51.7% were non-secretors. The proportion of non-secretors among individuals with renal scars in this study (42.6%) and that reported in the accompanying paper for Swedish children (40%) suggests that non-secretion might influence the pathogenic sequelae of these infections. Possible host-parasite interactions underlying the increased proportion of non-secretors among women with recurrent urinary tract infections and those leading to development of renal scars are discussed.     

Non-secretion of ABO blood group antigens: a host factor predisposing to recurrent urinary tract infections and renal scarring

Abstract In a study of 718 women referred for specialist investigation for recurrent urinary tract infections, 250 (34.8%, P <0.01) were non-secretors. The proportion of non-secretors among the women with renal scars (42.6%) was higher than that found for women with no evidence of renal scars (36.6%). Among 29 patients in whom symptoms began in childhood or adolescence, 51.7% were non-secretors. The proportion of non-secretors among individuals with renal scars in this study (42.6%) and that reported in the accompanying paper for Swedish children (40%) suggests that non-secretion might influence the pathogenic sequelae of these infections. Possible host-parasite interactions underlaying the increased proportion of non-secretors among women with recurrent urinary tract infections and those leading to development of renal scars are discussed.     

Gene amplification in multidrug-resistant cells: molecular and karyotypic events

The two theories of pancreatic enzyme secretion, those of exocytosis and transmembrane flow, are described. Data thought to support the theory of transmembrane flow of single molecules from pancreatic acinar cells are first reviewed, and the conditions which could allow these data to be explained by the theory of exocytosis of enzyme quanta, i.e. secretory granules, are then discussed. The evidence suggesting short-term modulation of the composition of pancreatic juice is also considered, and its possible explanations at the organ and cellular level are discussed, in the light of suggested theories on enzyme secretion pathways.     

Characteristics Of Patients With Ketosis-Prone Diabetes (Kpd) Presenting With Acute Pancreatitis: Implications For The Natural History And Etiology Of A Kpd Subgroup

ObjectiveReports of concomitant diabetic ketoacidosis (DKA) and acute pancreatitis (AP) are lacking among emerging forms of diabetes. This longitudinal study characterized ketosis-prone diabetes (KPD) in patients presenting with concomitant AP and DKA.MethodsMulti-ethnic KPD patients (N = 755) were followed prospectively for 1 year from the time of index DKA using repeated metabolic and beta cell functional reserve measures. Baseline and longitudinal characteristics were compared between KPD patients whose index DKA was associated with (n = 54) or without (n = 701) AP.ResultsThe AP group had significantly higher baseline serum amylase, lipase, and triglyceride levels and significantly lower bicarbonate levels than the non-AP group. AP patients had significantly greater C-peptide area-under-the-curve with glucagon stimulation shortly after the index DKA, and higher fasting C-peptide (FCP) levels 6 to 12 months later. Using the validated "Aβ" KPD classification, 85% of AP patients had β+ status (preserved beta cell functional reserve), compared to 60% of non-AP patients (P = .04). Multivariate analysis revealed that among the β+ KPD subgroup with an identifiable precipitating factor for DKA ("provoked" DKA), patients with AP had worse long-term glycemic outcomes than patients whose DKA was associated with other factors.ConclusionDespite greater clinical severity at presentation, KPD patients with AP have better preserved beta cell function than those without AP. β+ KPD patients presenting with AP have worse long-term glycemic control than those with other causes of provoked DKA. Factors other than beta cell function negatively impact glycemic control in KPD patients presenting with AP.