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Diabetologia May 2016In this review we discuss the mechanisms for the pleotropic effects of leptin replacement therapy to reverse liver and muscle insulin resistance in lipodystrophic... (Review)
Review
In this review we discuss the mechanisms for the pleotropic effects of leptin replacement therapy to reverse liver and muscle insulin resistance in lipodystrophic individuals, as well as insulin-independent effects of leptin replacement therapy to suppress white adipose tissue lipolysis, hepatic gluconeogenesis and fasting hyperglycaemia in rodent models of poorly controlled diabetes. On the basis of these studies we conclude with a view of the potential therapeutic applications of leptin replacement therapy in humans. This review summarises a presentation given at the 'Is leptin coming back?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Thomas Meek and Gregory Morton, DOI: 10.1007/s00125-016-3898-3 , and by Christoffer Clemmensen and colleagues, DOI: 10.1007/s00125-016-3906-7 ) and an overview by the Session Chair, Ulf Smith (DOI: 10.1007/s00125-016-3894-7 ).
Topics: Animals; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Humans; Insulin Resistance; Leptin
PubMed: 26961503
DOI: 10.1007/s00125-016-3909-4 -
International Journal of Medical... Jun 2023To establish a prediction model and assess the risk factors for severe diabetic ketoacidosis (DKA) in adult patients during the ICU.
Machine learning prediction models and nomogram to predict the risk of in-hospital death for severe DKA: A clinical study based on MIMIC-IV, eICU databases, and a college hospital ICU.
AIM
To establish a prediction model and assess the risk factors for severe diabetic ketoacidosis (DKA) in adult patients during the ICU.
INTRODUCTION
With DKA hospitalization rates consistently increasing, in-hospital mortality has become a growing concern.
METHODS
DKA patients aged >18 years old in the US-based critical care database (Medical Information Mart for Intensive Care (MIMIC-IV)) were considered. Independent risk factors for in-hospital mortality were screened using extreme gradient boosting (XGBoost) and the Bayesian information criterion (BIC) optimal subset regression. One predictive model was developed using machine learning extreme gradient boosting (XGBoost), and the other one was a nomogram based on logistic regression to estimate risks of in-hospital mortality with severe DKA. Established models were assessed by using internal validation and external validation. The MIMIC-IV was split into training and testing samples in a 7:3 ratio. The eICU Collaborative Research Database and admissions data from the department of critical care medicine of the first affiliated hospital of Harbin medical university were used for independent validation. The discriminatory ability of the model was determined by illustrating a receiver operating curve (ROC) and calculating the C-index. Meanwhile, the calibration plot and Hosmer-Lemeshow goodness-of-fit test (HL test) was conducted to evaluate the performance of our new build model. Decision curve analysis (DCA) was performed to assess the clinical net benefit. Net Reclassification Improvement (NRI) was used to compare the predictive power of the two models.
RESULTS
A multivariable model that included acute physiology score III (APS III), the highest levels of blood plasma osmolality (osmolarity_max), minimum osmolarity (osmolarity_min)/osmolarity _max, vasopressor, and the highest levels of blood lactate was represented as the nomogram. The C- index of the nomogram model was 0.915 (95% CI: 0.966-0.864) in the training dataset and 0.971 (95% CI: 0.992-0.950) in the internal validation. The nomogram's sensitivity was well according to all data's HL test (P > 0.05). DCA showed that our model was clinically valuable. The XGB (extreme gradient boosting) model achieved an AUC (area under the curve) of 0.950 (95% CI, 0.920-0.980); however, the nomogram model made was more effective than XGB based on NRI.
CONCLUSION
The predictive XGB and nomogram models for predicting in-hospital patient deaths with DKA were effective. The forecast models can help clinical physicians promptly identify patients at high risk of DKA, prevent in-hospital deaths, and promptly intervene.
Topics: Adult; Humans; Adolescent; Diabetic Ketoacidosis; Hospital Mortality; Bayes Theorem; Nomograms; Universities; Hospitals; Machine Learning; Intensive Care Units
PubMed: 37001474
DOI: 10.1016/j.ijmedinf.2023.105049 -
Annals of Saudi Medicine 2022Diabetic ketoacidosis (DKA) is one of the complications of diabetes mellitus (DM), primarily type 1 DM. To our knowledge, only one study explored DKA readmission rates...
BACKGROUND
Diabetic ketoacidosis (DKA) is one of the complications of diabetes mellitus (DM), primarily type 1 DM. To our knowledge, only one study explored DKA readmission rates in Saudi Arabia.
OBJECTIVES
Identify and analyze precipitating factors for DKA admission and readmission.
DESIGN
Medical record review.
SETTING
Tertiary care center.
PATIENTS AND METHODS
We identified all patients aged 15 years and older admitted with DKA from 2018 to 2020. Descriptive factors and uni-and multivariate analyses are presented for associations with initial admission and readmission.
MAIN OUTCOME MEASURES
Relationships between precipitating factors and initial admission and readmission.
SAMPLE SIZE
176 patients.
RESULTS
Most of the patients had type 1 DM (n=157). The median (interquartile percentiles) for duration of DM was 6.0 (1.0-12.0) years. The mean (SD) HbA1C (%) was 11.8 (2.6). The factors that precipitated DKA were most commonly treatment nonadherence (55.1%), followed by infections (31.8%) and nonadherence to diet (25.6%). The most common symptoms were nausea and vomiting (87.5%), followed by abdominal pain (72.7%). During the study period, 32.4% of the sample were read-mitted with DKA. The median (interquartile range) duration between the first and second admission was 12 (4-25) weeks. In the multivariate analysis, increased odds of readmission for DKA were associated with type 1 DM and medication nonadherence (=.038, =.013, respectively). The severity of the initial DKA and the control of DM were not associated with the readmission rate.
CONCLUSION
Treatment nonadherence is the leading precipitating factor of DKA in our region. Patient education and counseling play a major role in addressing this preventable complication and its medical and financial burden. We advocate more efforts dedicated toward patient education and logistic support.
LIMITATIONS
Retrospective-single center.
CONFLICT OF INTEREST
None.
Topics: Adolescent; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Humans; Patient Readmission; Retrospective Studies; Saudi Arabia
PubMed: 35380064
DOI: 10.5144/0256-4947.2022.119 -
Frontiers in Endocrinology 2022Considering the roles of 25-hydroxyvitamin D (25OHD) in glucose homeostasis and immune modulation, vitamin D deficiency may be related to the development of type 1...
BACKGROUND
Considering the roles of 25-hydroxyvitamin D (25OHD) in glucose homeostasis and immune modulation, vitamin D deficiency may be related to the development of type 1 diabetes (T1DM) and diabetic ketoacidosis (DKA). We evaluated the total, free, bioavailable 25OHD levels and vitamin D binding protein (VDBP) levels and genotypes between T1DM patients and controls.
METHODS
This retrospective, cross-sectional study included 84 children with T1DM (38 boys and 46 girls, 8.0 ± 3.6 years) and 1:1 age- and sex-matched healthy controls. A multiplex liquid chromatography-tandem mass spectrometry-based assay was used to simultaneously measure vitamin D metabolites.
RESULTS
Patients with T1DM had lower levels of total 25OHD (16.3 ± 5.1 vs. 19.9 ± 6.5 ng/mL, < 0.001) and VDBP (146.0 ± 27.8 vs. 224.9 ± 36.1 µg/mL, = 0.001), but higher free 25OHD (8.0 ± 2.5 vs. 6.5 ± 2.3 pg/mL, < 0.001) than controls. Patients who presented with DKA had lower levels of 25OHD in the total (15.0 ± 4.6 vs. 17.6 ± 5.2 ng/mL, = 0.020), free (7.5 ± 2.6 vs. 8.4 ± 2.4 pg/mL, = 0.059), and bioavailable (2.3 ± 0.9 vs. 2.8 ± 0.8 ng/mL, = 0.014) forms than those without DKA at the T1DM diagnosis. The lower the total, free, and bioavailable 25OHD levels at diagnosis, the lower the pH and HCO3-. The proportions of the VDBP genotypes did not differ between the patients and controls.
CONCLUSION
Patients with T1DM had higher levels of free 25OHD than healthy children, despite lower levels of total 25OHD. However, patients with DKA exhibited lower levels of bioavailable 25OHD than those without DKA at the T1DM diagnosis. The lower the concentrations of free and bioavailable 25OHD, the more severe the acidosis at the initial T1DM presentation.
Topics: Child; Male; Female; Humans; Diabetic Ketoacidosis; Diabetes Mellitus, Type 1; Cross-Sectional Studies; Retrospective Studies; Vitamin D
PubMed: 36339444
DOI: 10.3389/fendo.2022.997631 -
Journal of Osteopathic Medicine Sep 2023Diabetic ketoacidosis (DKA) is an endocrine emergency that can occur in people with diabetes. Its incidence is estimated to be 220,340 hospital admissions each year.... (Review)
Review
CONTEXT
Diabetic ketoacidosis (DKA) is an endocrine emergency that can occur in people with diabetes. Its incidence is estimated to be 220,340 hospital admissions each year. Treatment algorithms include fluid resuscitation, intravenous (IV) insulin infusion, and scheduled electrolyte and glucose monitoring. The misdiagnosis of DKA in the setting of hyperglycemic emergencies results in overtreatment and unnecessary increases in healthcare utilization and costs.
OBJECTIVES
The aims of this study were to determine how often DKA is overdiagnosed in the context of other acute hyperglycemic emergencies, to describe the baseline characteristics of patients, to determine the hospital treatments for DKA, and to identify the frequency of endocrinology or diabetology consultation in the hospital setting.
METHODS
A retrospective chart review was conducted utilizing charts from three different hospitals within a hospital system. Charts were identified utilizing ICD-10 codes for admissions to the hospital for DKA. If the patient was over 18 and had one of the diagnostic codes of interest, the chart was reviewed for further details regarding the criteria for DKA diagnosis as well as admission and treatment details.
RESULTS
A total of 520 hospital admissions were included for review. DKA was incorrectly diagnosed in 28.4 % of the hospital admissions reviewed, based on a review of the labs and DKA diagnostic criteria. Most patients were admitted to the intensive care unit (ICU) and treated with IV insulin infusion (n=288). Consultation of endocrinology or diabetology occurred in 40.2 % (n=209) of all hospital admissions, and 128 of those consults occurred in ICU admissions. The diagnosis of DKA was incorrect in 92 of the patients admitted to the medical surgical unit (MSU) and in 49 of patients admitted to the ICU.
CONCLUSIONS
Almost one third of hospital admissions for hyperglycemic emergencies were misdiagnosed and managed as DKA. DKA diagnostic criteria are specific; however, other diagnoses like hyperosmolar hyperglycemic syndrome (HHS), hyperglycemia, and euglycemic DKA can make an accurate diagnosis more complicated. Education directed at improving the diagnostic accuracy of DKA among healthcare providers is needed to improve diagnostic accuracy, ensure the appropriate use of hospital resources, and potentially reduce costs to the healthcare system.
Topics: Humans; Diabetic Ketoacidosis; Retrospective Studies; Emergencies; Blood Glucose Self-Monitoring; Blood Glucose; Hospitals; Insulins; Diabetes Mellitus
PubMed: 37406169
DOI: 10.1515/jom-2023-0019 -
BMJ Open Diabetes Research & Care Feb 2021Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM) characterized by hyperglycemia and metabolic acidosis. Hypophosphatemia... (Observational Study)
Observational Study
INTRODUCTION
Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM) characterized by hyperglycemia and metabolic acidosis. Hypophosphatemia in DKA often occurs during hospital admittance for DKA. Literature on the magnitude, determinants and consequences of hypophosphatemia in DKA is scarce. Primary aim of this study was to investigate the incidence and consequences of hypophosphatemia during hospitalisation for DKA.
RESEARCH DESIGN AND METHODS
Cohort study among individuals with T1DM who were admitted for DKA between 2005 and 2020 in an academic and a non-academic hospital. Multivariate regression models were performed to investigate determinants of the lowest phosphate during the treatment of DKA.
RESULTS
A total of 127 episodes of DKA among 80 individuals were identified. Age at DKA presentation was 28 (22-46) years, 45% of the cases was female, diabetes duration was 13.2 (8.9-25.5) years with glycosylated hemoglobin levels of 91.9±26.2 mmol/mol. In 9% of all cases, DKA was the first presentation of T1DM. Lowest phosphate levelss reported during the treatment phase were 0.54 (0.32-0.83) mmol/L and hypophosphatemia was present in 74% (62/84). The time to lowest phosphate was 16 (8-23) hours. In multivariate analysis, baseline bicarbonate and hemoglobin at admission were significantly associated with the lowest phosphate level reported. No adverse effects of hypophosphatemia on hospital stay duration, morbidity or mortality were found, even if left untreated.
CONCLUSIONS
Hypophosphatemia during DKA is common and increases with severe acidosis. However, in this study it was not related to adverse outcomes. Although limitations of this retrospective study should be taken into account, the routine and repeated measurement of phosphate levels in DKA could be reconsidered, provided that possible symptoms related to hypophosphatemia are monitored.
Topics: Cohort Studies; Diabetic Ketoacidosis; Female; Humans; Hypophosphatemia; Incidence; Retrospective Studies
PubMed: 33597187
DOI: 10.1136/bmjdrc-2020-002018 -
BMJ (Clinical Research Ed.) Jun 2007Saline should be used for fluid replacement rather than Hartmann's solution
Saline should be used for fluid replacement rather than Hartmann's solution
Topics: Diabetic Ketoacidosis; Fluid Therapy; Humans; Sodium Chloride
PubMed: 17585123
DOI: 10.1136/bmj.39237.661111.80 -
Journal of Diabetes and Its... Jan 2021"Brittle diabetes" was first used to describe a life "disrupted by episodes of hypoglycemia or hyperglycemia." Early descriptions focused on small case reports of mostly... (Review)
Review
"Brittle diabetes" was first used to describe a life "disrupted by episodes of hypoglycemia or hyperglycemia." Early descriptions focused on small case reports of mostly young women with psycho-social instability, recurrent diabetic ketoacidosis, poor patient compliance or maladaptation. We redefine "brittle diabetes" as occurring in four specific life stages each with distinct characteristics and associated conditions resulting in severely erratic glycemic control and poor outcomes. Once identified however these factors can often be reversed or significantly mitigated. The first group includes younger patients with associated psychiatric diseases such as bulimia and depression which require specific therapy and are treatable. A second group includes individuals who have another underlying medical condition resulting in disruption of insulin sensitivity or glucose utilization which must be sought. A third group, the largest we believe, has "geriatric type 1 diabetes" and develops severe glycemic instability due to frailty, chronic renal failure, dementia, vision loss, loss of counterregulation and other diseases of aging which lead to unintentional omission of insulin, insulin dosing errors and increasing insulin sensitivity. The fourth group, now seen around the world, suffers lack of insulin access and associated food insecurity. All four of these groups are described.
Topics: Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Hypoglycemia; Insulin; Insulin Resistance; Insulin, Regular, Human
PubMed: 32620472
DOI: 10.1016/j.jdiacomp.2020.107646 -
PloS One 2021Diabetic ketoacidosis (DKA) is a serious complication of complete insulin deficiency and insulin resistance in Type 1 diabetes (T1D). This results in the body producing...
Diabetic ketoacidosis (DKA) is a serious complication of complete insulin deficiency and insulin resistance in Type 1 diabetes (T1D). This results in the body producing high levels of serum ketones in an attempt to compensate for the insulin deficiency and decreased glucose utilization. DKA's metabolic and immunologic dysregulation results in gradual increase of systemic and cerebral oxidative stress, along with low grade systemic and cerebral inflammation and the development of pretreatment subclinical BE. During treatment the early progression of oxidative stress and inflammation is hypothesized to advance the possibility of occurrence of crisis of clinical brain edema (BE), which is the most important cause of morbidity and mortality in pediatric DKA. Longitudinal neurocognitive studies after DKA treatment show progressive and latent deficits of cognition and emphasize the need for more effective DKA treatment of this long-standing conundrum of clinical BE, in the presence of systemic osmotic dehydration, metabolic acidosis and immune dysregulation. Candidate biomarkers of several systemic and neuroinflammatory pathways prior to treatment also progress during treatment, such as the neurotoxic and neuroprotective molecules in the well-recognized tryptophan (TRP)/kynurenine pathway (KP) that have not been investigated in DKA. We used LC-MS/MS targeted mass spectrometry analysis to determine the presence and initiation of the TRP/KP at three time points: A) 6-12 hours after initiation of treatment; B) 2 weeks; and C) 3 months following DKA treatment to determine if they might be involved in the pathogenesis of the acute vasogenic complication of DKA/BE. The Trp/KP metabolites TRP, KYN, quinolinic acid (QA), xanthurnenic acid (XA), and picolinic acid (PA) followed a similar pattern of lower levels in early treatment, with subsequent increases. Time point A compared to Time points B and C were similar to the pattern of sRAGE, lactate and pyruvic acid. The serotonin/melatonin metabolites also followed a similar pattern of lower quantities at the early stages of treatment compared to 3 months after treatment. In addition, glutamate, n-acetylglutamate, glutamine, and taurine were all lower at early treatment compared to 3 months, while the ketones 3-hydroxybutaric acid and acetoacetate were significantly higher in the early treatment compared to 3 months. The two major fat metabolites, L-carnitine and acetyl-L-carnitine (ALC) changed inversely, with ALC significantly decreasing at 2 weeks and 3 months compared to the early stages of treatment. Both anthranilic acid (AA) and 3-OH-anthranilic acid (3OH-AA) had overall higher levels in the early stages of treatment (A) compared to Time points (B and C). Interestingly, the levels of AA and 3OH-AA early in treatment were higher in Caucasian females compared to African American females. There were also differences in the metabolite levels of QA and kynurenic acid (KA) between genders and between races that may be important for further development of custom targeted treatments. We hypothesize that the TRP/KP, along with the other inflammatory pathways, is an active participant in the metabolic and immunologic pathogenesis of DKA's acute and chronic insults.
Topics: Adolescent; Child; Chromatography, Liquid; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glucose; Humans; Kynurenine; Male; Metabolic Networks and Pathways; Quinolinic Acid; Tandem Mass Spectrometry; Tryptophan
PubMed: 34280211
DOI: 10.1371/journal.pone.0254116 -
Journal of Medical Case Reports Oct 2022Mucormycosis is a rare, life-threatening fungal infection that affects immunocompromised hosts. Diabetes mellitus is a common predisposing condition and most often...
BACKGROUND
Mucormycosis is a rare, life-threatening fungal infection that affects immunocompromised hosts. Diabetes mellitus is a common predisposing condition and most often presents with rhino-orbital-cerebral infection. Association with coronavirus disease 2019 infection was revealed following a resurgence in cases of mucormycosis during the second wave of the pandemic wherein poorly controlled diabetes mellitus was the most significant risk factor in the affected population. Rhino-orbital-cerebral mucormycosis has a high mortality rate, and cerebral involvement is a poor prognostic factor. Herein, we report a case of newly diagnosed diabetes mellitus with concurrent coronavirus disease 2019 infection complicated by diabetic ketoacidosis and rhinocerebral mucormycosis at presentation, describe the diagnostic and therapeutic challenges, and discuss the interventions that ultimately resulted in a favorable clinical response.
CASE PRESENTATION
We describe the case of a previously healthy 13-year-old African American female patient with newly diagnosed diabetes mellitus and concurrent severe acute respiratory syndrome coronavirus 2 infection whose disease course was complicated by rhinocerebral mucormycosis. She presented with fever, altered mental status, and Kussmaul respirations and was diagnosed with diabetic ketoacidosis with concern for cerebral edema. Concern for infectious cerebritis arose due to recurring fevers and persistently altered mental status despite correction of her metabolic derangements. This raised concern for infectious cerebritis and prompted evaluation with serial head imaging, lumbar puncture, and initiation of broad empiric antimicrobial regimen. Head imaging revealed an evolving cerebral abscess, and fungal deoxyribonucleic acid was identified on blood metagenomics testing, which ultimately confirmed the diagnosis of rhinocerebral mucormycosis. Treatment was challenging as she required surgical debridement of the frontal lobe and aggressive antifungal therapy complicated by electrolyte derangements and electrocardiogram changes that necessitated modification of the antimicrobial regimen. Despite these challenges and high mortality rate, the patient was discharged from the hospital in stable condition to inpatient rehabilitation service for reconditioning after prolonged hospitalization.
CONCLUSION
Rhinocerebral mucormycosis mortality is associated with delays in therapeutic interventions, thus a high index of suspicion and early recognition were essential for timely initiation of antifungal therapy and surgical debridement.
Topics: Female; Humans; Adolescent; Mucormycosis; Diabetic Ketoacidosis; COVID-19; Antifungal Agents; Brain Abscess; Encephalitis; Diabetes Mellitus
PubMed: 36316719
DOI: 10.1186/s13256-022-03594-2