History Of Diabetic Ketoacidosis Research Articles

Characteristics and Treatment Outcome of Pediatric Diabetic Ketoacidosis in Mekong Delta, Vietnam: A 5-Year Retrospective Study

Background Diabetic ketoacidosis (DKA), a critical and potentially fatal complication resulting from a lack of insulin, presents with elevated blood sugar, acid-base imbalance, and increased ketone bodies. Objectives Our research was designed to assess the clinical manifestations, laboratory findings, and outcomes of treatment in children diagnosed with DKA over a span of five years in the Mekong Delta region of Vietnam. Methods This study retrospectively analyzed pediatric cases of diabetic ketoacidosis treated at a major pediatric center in the Mekong Delta between 2017 and 2021. Results Diabetic ketoacidosis was more common in older children aged 11 – 16 years (66.7%), and females (70%). The majority of cases had not been diagnosed with previous diabetes (60%) and no history of diabetic ketoacidosis (90%). In univariate analysis, female gender (OR, 13.0; 95% CI, 1.4 – 124.3; p=0.026), previous diabetes diagnosis (OR, 7.8; 95% CI, 1.5 – 41.2; p=0.016), precipitating factors (OR, 10.1; 95% CI, 1.1 – 97.0; p=0.045), tachypnea (OR, 5.5; 95% CI, 1.1 – 26.4; p=0.033), Kussmaul breathing (OR, 5.4; 95% CI, 1.1 – 26.0; p=0.036), serum potassium level (OR, 3.5; 95% CI, 1.2 – 10.4; p=0.027), and anion gap (OR, 1.6; 95% CI, 1.8 – 2.3; p=0.003) were associated factors with severe DKA. All cases in our study had a 100% survival rate. Anion gap was an independent factor associated with severe diabetic ketoacidosis after adjustment multivariate analysis. Conclusion: Female, younger age, precipitating factors, tachypnea, Kussmaul’s breathing, and relevant laboratory findings, including increased anion gap, should be considered to ensure successful management in pediatric diabetic ketoacidosis. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 1112-1119

Diabetic ketoacidosis resolution: From the traditional way to guideline-based management in the MICU at University Medical Center, Lubbock, Texas

Diabetes is a chronic, metabolic disease characterized by hyperglycemia which eventually can cause serious organ damage. The prevalence of diabetes has steadily increased over the past few decades, and approximately 1.4 million Americans are diagnosed with diabetes every year. Diabetes was the seventh leading cause of death in the United States in 2019. Diabetic ketoacidosis (DKA) is a serious complication of diabetes that can be life-threatening. It occurs more frequently in the patients with type 1 diabetes but can also develop in people with type 2 diabetes. It was determined that the average cost per DKA episode was $6,444, and that the annual cost of medical treatment in a diabetic patient with a prior episode of DKA was 2.67 times higher than a diabetic patient with no history of DKA. The criteria for DKA resolution at University Medical Center (UMC) in Lubbock, Texas, are different from current American Diabetes Association (ADA) guidelines. At UMC, a plasma bicarbonate ≥18 mEq/L, a venous pH > 7.3, and anion gap ≤12 mEq/L must be recorded twice (4 hours apart) before bridging to subcutaneous long-acting insulin administration. This time requirement could contribute to a longer time for DKA resolution and longer intensive care unit and hospital stays.Keywords: Diabetic ketoacidosis, DKA resolution

Impact Of The Covid-19 Pandemic On Glycemic Control In Childhood Type 1 DM Patients

There has been an increase in cases of diabetic ketoacidosis in children aged 1-14 years from 73% in 2019 to 83% in 2020 during the COVID-19 pandemic. An increase in acute complications of type-1 DM can occur due to lack of compliance with glycemic control and activity restrictions which have the impact of reducing the level of glycemic control in children with type-1 DM. Based on these findings, researchers wanted to know the impact of restrictions on community activities during pandemic on the glycemic control of children with type 1 DM. The aims of this study is to determine the impact of the COVID-19 pandemic on glycemic control through HbA1c parameters in children with type 1 DM. Methods of this research is a cross sectional study with a sample size of 26 patients. Results are The average age of respondents was 15.58 years. More than half of respondents were female (73.1%). The average duration of suffering from type 1 DM was 4.77 years. More than half of the respondents had a history of diabetic ketoacidosis, 53.8%, and all respondents were Health Insurance (BPJS) participants (100%). There was a decrease in HbA1c levels during the pandemic compared to before the pandemic, namely 12.17 ± 2.60 to 10.32 ± 2.21. Statistically, this decrease means that there is an impact of the COVID-19 pandemic on glycemic control through the HbA1c parameter in children with type 1 DM (p<0.05). There was a decrease in HbA1c levels during the pandemic compared to before the pandemic.

Relationship Between Children's Cognitive Function and Type 1 Diabetes Mellitus (T1DM): A Systematic Review

Background: Type 1 diabetes mellitus (T1DM) is the most common type of diabetes in children and is caused by various factors, including immune system abnormalities, genetic factors, and environmental influences. T1DM usually occurs in early to mid-childhood when an autoimmune process damages the pancreas's beta cells, producing insufficient insulin. Purpose: Review several studies on T1DM associated with cognitive decline in children. Methods: The study systematically reviews five articles from randomized controlled trials, focusing on the cognitive function of children with T1DM. It specifically explored the relationship between T1DM, cognitive deficits, and the impact of diabetic ketoacidosis on cognitive function in children. Results: This review included five articles from randomized controlled trials between 1999 and 2023, distributed across two nations. The studies included 1.579 children with T1DM or with Ketoacidosis diabetic. Sample testing with cognitive function measurements in each article. Discussion: Type 1 diabetes patients had milder to moderate cognitive deficits on a variety of neuropsychological tests compared with nondiabetic control subjects. These cognitive deficits are primarily related to mental processing speed, executive function, and memory. Summary: Children with T1DM, especially those with a history of diabetic ketoacidosis, exhibited mild to moderate cognitive deficits, particularly in mental processing speed, executive function, and memory. The review emphasized the potential impact of T1DM on children's cognitive development and academic performance, underscoring the need for early diagnosis and appropriate management to mitigate cognitive decline.

Effect of metabolic control on cognitive functions in children and adolescents with type 1 diabetes mellitus.

Neurocognitive functions of children with type 1 diabetes mellitus (T1D) are reported to be poorer than those of healthy peers. The aim was to investigate the effects of age of onset of diabetes, metabolic control, and type of insulin regimen on neurocognitive functions in children and adolescents with T1D. Forty-seven children aged 6-18 years, with T1D for at least five years, were included. Children with a known psychiatric disorder or chronic diseases other than T1D were excluded. Intelligence via the Wechsler children's intelligence scale (WISC-R), short-term memory via the audio-auditory digits form B (GISD-B) test, visual motor perception via the Bender Gestalt test, and attention via the Moxo continuous attention and performance test, timing, hyperactivity, and impulsivity (Moxo-dCPT) were assessed. Compared with the T1D group, healthy controls had higher scores in terms of verbal intelligence quotient (IQ), performance IQ, and total IQ mean scores on WISC-R (p=0.01, p=0.05 and p=0.01, respectively). On the MOXO-dCPT test, the T1D group had higher impulsivity compared to the control group (p=0.04). Verbal IQ was better in the moderate control group than in the poorer metabolic control (p=0.01). Patients with no history of diabetic ketoacidosis (DKA) had higher performance, verbal and total intelligence scores than the group with history of DKA. Poor metabolic control and a history of DKA in children with T1D adversely affected neurocognitive functions. It would be beneficial to consider the assessment of neurocognitive functions in T1D and to take the necessary precautions in follow-up.

Clinical and biochemical profile of childhood-adolescent-onset type 1 diabetes and adult-onset type 1 diabetes among Asian Indians.

To compare the clinical and biochemical profile and prevalence of complications among childhood/adolescent-onset (CAO; onset of diabetes< 20years of age) and adult-onset (AO; onset of diabetes- ≥ 20years of age) type 1 diabetes (T1D), seen at a tertiary care diabetes center in south India. Data of 5578 individuals with T1D, diagnosedbased on a history of diabetic ketoacidosis or ketonuria, fasting C-peptide < 0.3pmol/mL and stimulated C-peptide values < 0.6pmol/mL, and requirement of insulin right from the time of diagnosis, presenting to our center between 1991 and 2021, were retrieved fromour electronic medical records. Retinopathy was assessed by retinal photography, chronic kidney disease (CKD) by urinary albumin excretion ≥ 30µg/mg of creatinine and/or eGFR < 60mL/min, and neuropathy by vibration perception threshold >= 20v on biothesiometry. Overall, 3559 (63.8%) of individualswith T1D, belonged to CAO group and 2019 (36.2%) to AO category. AO had higher prevalence of all microvascular complications compared to CAO at every diabetes duration interval, even after adjusting for A1c. Among the AO group, prevalence of retinopathy, CKD, and neuropathy was higher in the GAD negative group. Among CAO there were no differences between the GAD negative and GAD positive groups with respect to prevalence of complications of diabetes. AO with T1D had higher prevalence of microvascular complications compared to CAO. Among AO, GAD negative individuals had higher percentage of retinopathy and CKD compared to GAD positive group.

PSUN330 Patients with Recurrent Hypoglycemia Encounters Across Chicago: Who are they?

Abstract Hypoglycemia is an acute complication of diabetes management that has been linked to increased morbidity. Although current guidelines have called for treatment changes for avoidance of hypoglycemia, it remains a critical issue. Our goal was to examine the socio-demographic and clinical factors for recurrent hypoglycemic encounters across a large metropolitan area. CAPriCORN is a research network which brings together merged, de-duplicated, and de-identified electronic medical health record data from 6 institutions across Chicago. Patients with a diabetes diagnosis and hypoglycemic encounters (HEs) between 2011-18 were identified using ICD-9 and 10 codes. HEs were identified using a validated algorithm. Analysis was performed to evaluate the patient characteristic differences between patients with 1 vs 2-3 vs ≥4 HEs utilizing chi-square for categorical variables and ANOVA for continuous variables. Of 423,643 patients identified with a diagnosis of diabetes, 17,885 (4%) patients had at least one diagnosis of hypoglycemia, which included 30,157 unique encounters (1 HE: 12,886 pts and encounters; 2-3: 3,640 pts and 8,238 encounters, and ≥4: 1,359 pts and 9,033 encounters). The 1,359 patients with ≥4 HEs (8% of all patients with HEs) accounted for over 30% of all HEs. Older adults (65 years and older) comprised 57% of all patients and 62% of patients with HEs. Older adults comprised 63% of those with 1 HE, 61% of those with 2-3, and 52% of those with ≥ 4 (p&amp;lt; 0.001). Adults 80 years and older represented &amp;gt; 20% of those in each group. Whites (N=7,203, 40%) and Blacks (N=6,511, 36%) accounted for most with HE, and within each category. Overall, among those with 1, 2-3, and ≥ 4 HEs there were also significant differences by race and ethnicity. Patients with a HE had significant history of complications, including 54% with nephropathy, 24% with neuropathy, and 23% with ophthalmologic complications. However, a history of diabetic ketoacidosis (DKA) was noted in 53% of all patients with a HE, with 49%, 61%, and 66% of patients in 1, 2-3, and ≥4 HEs groups, respectively (p&amp;lt;0.001). Of those with medication information (n=8,938), patients on insulin-only therapy represented 47% of patients with a HE, and 44%, 52%, and 65% of patients who had 1, 2-3, and ≥4 HEs, respectively (p&amp;lt;0.001). Patients on sulfonylureas or meglitinides represented 28% of patients with a HE, and 31%, 25%, and 15% of patients who had 1, 2-3, ≥4 HEs, respectively (p&amp;lt;0.001). Of those with lab information for HbA1c (n=5,259) there was no significant difference between groups. Overall, a small diverse group of patients accounted for a large amount of hypoglycemic encounters. Special attention should be paid to subsets of patients, including older adults, those with a history of DKA, and those on high-risk therapy. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

SODIUM-GLUCOSE TRANSPORT PROTEIN 2 INHIBITOR ELIGIBILITY FOR PATIENTS HOSPITALIZED WITH ACUTE HEART FAILURE

SODIUM-GLUCOSE TRANSPORT PROTEIN 2 INHIBITOR ELIGIBILITY FOR PATIENTS HOSPITALIZED WITH ACUTE HEART FAILURE

170-LB: Identifying Atypical Diabetes Using i2b2 Algorithms in Electronic Health Records

Investigating atypical forms of diabetes (other than types 1 or 2, monogenic or secondary) is the focus of research in the Rare and Atypical Diabetes Network (RADIANT) . It is difficult to identify persons with atypical diabetes using standard electronic health record (EHR) queries because there are no specific ICD codes for these phenotypes and wide range of clinical features. We aimed to develop an algorithm to identify individuals with searchable characteristics of atypical diabetes within the Baylor Medicine EHR using Informatics for Integrating Biology at the Bedside (i2b2) . I2b2 enables integration, standardization, and analysis of heterogenous quantitative and qualitative data from healthcare and research databases. Our i2b2 algorithm intended to look for patients coded as type 2 diabetes (T2D) but were very lean and lacked clinical features suggestive of systemic insulin resistance. We included new patient visits with ICD codes for T2D in the past year but excluded those with BMI &amp;gt;20 kg/m2 and triglycerides &amp;gt;100 mg/dL, or ICD codes for hypertension and hyperlipidemia. Next, we excluded patients with secondary causes of diabetes (cystic fibrosis, acromegaly, Cushing's syndrome, chronic/acute pancreatitis or presence of islet autoantibodies (GAD65Ab, IA2Ab) . The algorithm identified 133 persons from a total EHR population of 3,685,797. Manual chart review confirmed that 18 patients (13.5%) met RADIANT criteria for atypical diabetes, while information was missing in the EHR to fully classify 8 patients (6%) and 1 patient was deceased (0.8%) . Those who fully met criteria for atypical diabetes had the following characteristics: 72% female, median BMI at diagnosis 19.8 kg/m2, median age at diagnosis 29 y, 75% with history of diabetic ketoacidosis and 19.5% currently on insulin. Algorithms built on data platforms such as i2b2 may be helpful in identifying patients who should be evaluated for atypical diabetes within standard EHR databases. They could optimize recruitment for research, identify disease trends and permit improved classification of diabetes subgroups. Disclosure N. Kikani: None. G. Montes: None. R. Gaba: None. G. Liao: None. M. Tosur: Advisory Panel; Provention Bio, Inc. M. J. Redondo: Advisory Panel; Provention Bio, Inc. A. Balasubramanyam: None. Funding The RADIANT Study is funded by U54 DK118638 and U54 DK118612 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Medical nutrition therapy and home monitoring in type 2 diabetes mellitus patient with metabolic syndrome and history of diabetic ketoacidosis

Obesity, one of the risk factors for mtype 2 diabetes mellitus (T2DM), is known to cause low-grade inflammation and increase T2DM morbidity. Obesity and T2DM also lead to other comorbidities, such as metabolic syndrome. The provision of medical nutrition therapy accompanied with routine home monitoring could improve glycemic control and achieve therapeutic targets, simultaneously.

Diabetic ketoacidosis: a canary in the mine for mental health disorders?

Recurrent diabetic ketoacidosis (DKA) has been linked to mental health disorders, but less is known about single DKA episodes. Most studies are retrospective, lacking control groups. To prospectively examine psychosocial factors in patients presenting with recurrent or single episode DKA and compare with people who have not had DKA. Case-controlled study (consecutive adult DKA admissions April 2015 to December 2016) at Western Health, Melbourne. Data were prospectively collected regarding diagnosed mental health disorders, likely depression (Patient Health Questionnaire (PHQ-9)), diabetes distress (Problem Areas in Diabetes (PAID) questionnaire) and presence of adverse social factors. A control group without a history of DKA was also recruited. Of 123 patients admitted with DKA (164 consecutive episodes), 70 consented to participate and 73 age-matched Type 1 diabetes controls were recruited. Eleven (61%) of 18 with recurrent DKA had a diagnosed mental health disorder versus 8 (19%) of 42 in the single episode group (P = 0.016). The prevalence of likely depression using PHQ-9 was: recurrent 50%; single 40%; and controls 22% (recurrent vs controls, P = 0.036; single vs controls, P = 0.053). Severe diabetes distress (PAID) was present in 47% of recurrent and 34% of single episode DKA (P = 0.387). As a group, DKA patients had significantly more unemployment, illicit drug use and tobacco smoking, a lower level of formal education and less regular medical contact compared with controls. Mental health disorders and adverse socioeconomic factors appear to be common in patients with DKA. The diagnosis of DKA presents an excellent opportunity to screen for depression and offer appropriate intervention.

An atypical case report of extensive mucormycotic osteomyelitis of maxilla as a consequence of post-COVID complication

Saprophytic molds such as Mucor, Rhizopus, and Absidia cause mucormycosis, a fungal infection. These saprophytic fungi are common in the environment and have a strong proclivity for invading major blood arteries, causing tissue ischemia, necrosis, and infarction. They have been linked to immunocompromised individuals with a history of diabetic ketoacidosis, corticosteroid medication, HIV infection, malignant lymphomas, and patients currently receiving and recovering from COVID-19 treatment. The foregoing is the case of a 78-year-old COVID-19 recovered male who presented with a primary complaint of upper tooth movement for 1 month and maxillary segmental mobility. The maxillary alveolar process was resected, and histopathological reports revealed mucormycosis, which was treated with antifungal medication and nasolabial flap surgery. For the past 6 months, he has been disease-free. Early detection and treatment may offer a higher chance of successfully minimizing this debilitating condition.

Relationship Between Bedside Ketone Levels and Time to Resolution of Diabetic Ketoacidosis: A Retrospective Cohort Study

IntroductionThere is no information on the factors that influence the time required to induce resolution of diabetic ketoacidosis (DKA). New methods are currently available for bedside measurement of serum 3-hydroxybutyrate (3HB). The aim of this study was to determine the relationship between serum 3HB and the time to DKA resolution.MethodsWe reviewed the medical records of patients with type 1 diabetes (T1D) and a history of DKA who were admitted to the Department of Pediatrics, Osaka City University Hospital, between November 2008 and October 2018. DKA resolution was defined as 3HB below 1.0 mmol/L as measured by a bedside ketone meter.ResultsData of 52 T1D-DKA episodes were analyzed (median age, 8.0 years; 20 male patients; 32 female patients; new T1D diagnosis, n = 13; established diagnosis, n = 39). In all cases, correction of serum 3HB was an important aspect of T1D management. The median time to DKA resolution (defined as the time from the start of insulin infusion until the fall of 3HB level to below 1.0 mmol/L) was 11 and 10 h in new and established T1D cases, respectively. 3HB on admission and the required insulin infusion dose per body weight, but not blood pH level on admission, correlated with time to DKA resolution. There was no relationship between blood pH level and 3HB on admission.ConclusionsOur results showed that DKA resolution could be achieved within 10–11 h when DKA treatment is guided by bedside 3HB monitoring without any severe complications. Blood 3HB level is a potentially suitable marker for the severity and resolution of DKA.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01167-y.

DISSEMINATED MULTIFOCAL MUCORMYCOSIS TREATED WITH A COMBINATION ANTIFUNGAL REGIMEN

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Rhinocerebral mucormycosis is a fatal infection in poorly controlled diabetic patients with a history of diabetic ketoacidosis (DKA). DKA blunts neutrophil chemotaxis, phagocytosis and boosts serum iron, a mucor nutrient. It spreads to the brain via the hematogenous or contiguous spread [1]. We present a case of disseminated rhinocerebral mucormycosis in a diabetic patient on treatment with a combination antifungal regimen CASE PRESENTATION: A 22-year-old poorly controlled diabetic with a hemoglobin A1c of 14.1% was admitted to an outside hospital for a week of chest pain, dyspnea, fever, and dry cough with recently diagnosed coronavirus disease 2019. She was treated for DKA. Four days later, she developed a new-onset right-sided vision loss, ptosis, areflexic pupil, eye abduction loss, and bloody nasal mucus drainage. Computed tomography (CT) of the chest was normal. CT angiogram (CTA) of the head and neck showed occlusion of the right ophthalmic artery and the superior ophthalmic vein. Magnetic resonance imaging (MRI) showed subacute right frontal infarct and chronic sinusitis. An oral exam disclosed a large hard palate necrotic area, which on biopsy culture grew Rhizopus oryzae (Figure A-B). She was transferred to our facility for further surgical debridement. On arrival, she was placed on high-dose liposomal amphotericin (LAmB) and euglycemic control. A cerebral angiogram revealed right internal carotid artery occlusion. MRI showed right cavernous sinus thrombosis, right ophthalmic artery mycotic aneurysm, paranasal sinusitis with right sphenoid fungal sinusitis extending into gyri rectus, and watershed infarcts in the right middle and anterior cerebral artery territories (Figure C1). Neurosurgery deferred surgical debridement. Later caspofungin and deferasirox were added adjunctively for two weeks with surgical debridements and a week of hyperbaric oxygen, after which MRI findings improved (Figure C2). She is clinically improving on LAmB and caspofungin DISCUSSION: Combination regimens are ineffective in neutropenic or cancer patients [2,3]. LAmB and deferasirox with or without an echinocandin/posaconazole have been effective in diabetics with intracranial lesions [2]. Combination regimen efficacy has been observed in diabetic mice and anecdotal case reports [3,4]. This is due to prompt recovery of neutrophil function and loss of glucose-regulated protein78 mediated Rhizopus angioinvasion once acidosis and hyperglycemia are corrected [5] CONCLUSIONS: To improve diabetic patient outcomes, a timely diagnosis, prompt reversal of DKA and hyperglycemia, along with surgical debridement and antifungal therapy, are of immense importance. Combination antifungal therapy may benefit cases where complete surgical debridement is not achievable REFERENCE #1: Mallis A, Mastronikolis SN, Naxakis SS, Papadas AT. Rhinocerebral mucormycosis: an update. Eur Rev Med Pharmacol Sci. 2010;14(11):987-92 DISCLOSURES: No relevant relationships by Mohammed Alnijoumi, source=Web Response No relevant relationships by Phillip Beck, source=Web Response No relevant relationships by Paragkumar Patel, source=Web Response No relevant relationships by SACHIN PATIL, source=Web Response No relevant relationships by Deepthi Rao, source=Web Response No relevant relationships by Hariharan Regunath, source=Web Response No relevant relationships by Blaine Winterton, source=Web Response

The Epidemiology and Genetic Analysis of Children With Idiopathic Type 1 Diabetes in the State of Qatar.

ContextIdiopathic type 1 diabetes is characterized by the absence of autoantibodies and the underlying mechanisms are not clear.ObjectiveWe aimed to study the epidemiology, describe the clinical characteristics, and report results of genetic studies in pediatric patients with idiopathic type 1 diabetes.MethodsThis was a prospective study of type 1 diabetes patients attending Sidra Medicine from 2018 to 2020. Autoantibodies (GAD65, IAA, IA-2A, and ZnT8) were measured and genetic testing was undertaken in patients negative for autoantibodies to rule out monogenic diabetes. Demographic and clinical data of patients with idiopathic type 1 diabetes were compared with patients with autoimmune type 1 diabetes.ResultsOf 1157 patients with type 1 diabetes, 63 were antibody-negative. Upon genome sequencing, 4 had maturity onset diabetes of the young (MODY), 2 had Wolfram syndrome, 1 had H syndrome, and 3 had variants of uncertain significance in MODY genes; 53 patients had idiopathic type 1 diabetes. The most common age of diagnosis was 10 to 14 years. C-peptide level was low but detectable in 30 patients (56.6%) and normal in 23 patients (43.4%) The average body mass index was in the normal range and 33% of the patients had a history of diabetic ketoacidosis (DKA).ConclusionFour percent of the children had idiopathic type 1 diabetes. There were statistically significant differences in the C-peptide level and insulin requirement between the 2 groups. DKA was less common in the idiopathic group. Mutations in MODY genes suggest the importance of autoantibody testing and genetic screening for known causes of monogenic diabetes in idiopathic type 1 diabetes. The mechanism of idiopathic type 1 diabetes is unknown but could be due to defects in antibody production or due to autoantibodies that are not yet detectable or discovered.

Clinical experience from a regional monogenic diabetes referral centre in Singapore

AimsMonogenic diabetes (also known as maturity-onset diabetes of the young or MODY) affects a subset of individuals with young-onset diabetes. We report our diagnostic work-up experience for such individuals. MethodsServing as a regional secondary-care diabetes centre in a multi-ethnic population, we receive referrals to evaluate MODY from endocrinologists in both public and private practice. Key criteria for consideration of genetic-testing are onset age ≤ 35, negative GAD antibody, no history of diabetic ketoacidosis, strong family history of diabetes and BMI < 32.5 kg/m2. A monogenic diabetes registry was set up since 2017 to study their disease trajectories. ResultsWe identified 30 out of 175 (17.1%) individuals with likely pathogenic/pathogenic variants. Importantly, 29 out of 30 (96.7%) occurred in clinically actionable genes. A continuous scale combining BMI, hs-CRP and HDL provided 80% (P < 0.001) diagnostic accuracy for MODY in our cohort, achieving a negative predictive value of 0.93 and sensitivity at 0.76. Subtyping MODY prior to genetic testing (if desired) will require specialist domain knowledge and additional biomarkers due to its genetic heterogeneity. ConclusionsThrough systematic and structured evaluation, the prevalence of MODY is non-trivial (17.1%) in a referral centre. Diagnostic algorithm combining clinical criteria and readily available biomarkers can support clinical decision for MODY genetic testing.

P1035URINARY HEME OXYGENASE 1 AS A MARKER FOR EARLY DIAGNOSIS OF DIABETIC NEPHROPATHY

Abstract Background and Aims Heme oxygenase 1 is an essential enzyme in heme catabolism induced by oxidative stress.It induced in avariety of kidney substructres in response to injury, including proximal tubules, glomeruli and renal interstitium.We aimed to assess the possible role of heme Oxygenase-1 as a potential marker in early diagnosis of diabetic nephropathy. Method This case control study was conducted in Ain Shams university hospital, Cairo, Egypt. It included 80 type 2 diabetic patients diagnosed according to the American Diabetes Association (ADA) criteria, with and without DN ,and 20 healthy control subjects matched in age and sex .Patients were divided into two groups according to the value of the urinary albumin-to-creatinine ratio (ACR) : Group I: 40 normoalbuminuric patients(16 M and 24 F) with ACR&amp;lt;30 mg/g, and Group II: 40 microalbuminuric patients (18M and 22 F) with ACR 30-300mg/g. We excluded patients with history of diabetic ketoacidosis or hypoglycemic coma in the past 3 months preceding the study. Patients with glomerulonephritis, nephrolithiasis, tumors or any other renal diseases were excluded as well. For all studied groups,full history taking and clinical examination were done. We assessed glycosylated hemoglobin (HbA1C),blood urea, serum creatinine, urine creatinine, urinary albumin-to creatinine ratio (ACR mg/g) ,and urinary hemeoxygenase 1(UHO-1) by ELISA . Glomerular filtration rate (eGFR) was estimated by modification of diet in renal disease formula(MDRD)and uHO-1/cr was calculated. Results Group I patients were diabetic for 6.18±0.75 years, while group II patients for 6.05±0.81 years(p = 0.477). Normoalbuminuric patients had significantly higher levels of uHO-1 compared to control (3.01ng/ml vs 0.3 ng/ml,p&amp;lt;0.001).UHO-1 reached highest value among the microalbuminuric group (5.02 ng/ml) with P&amp;lt;0.001.UHO-1/cr ratio was significantly positively correlated with urinary ACR (r = 0.61,p&amp;lt;0.001) and significantly negatively correlated with eGFR(r = -0.71,p &amp;lt;0.001). There was highly significant correlation between uHO-1and eGFR by linear regression. ROC curves showed that AUC of uHO-1is comparable to uHO-1/ Cr ratio (0.957 vs 0.954) respectively with equivocal sensitivity 100 % and specificity 95% and cut off value of uHO-1 &amp;gt;0.46 ng/mland &amp;gt; 0.7 for uHO-1/ Cr ratio. Conclusion UHO-1 is increased in normoalbuminuric patients before the presence of any proteinuria and level increased with the progression of proteinuria and falling of eGFR as well as with the uncontrol of diabetes. UHO-1 is more sensitive than albumin for the detection of early diabetic nephropathy.

Effects of Diabetic Ketoacidosis on Executive Function in Children With Type 1 Diabetes: Evidence From Wisconsin Card Sorting Test Performance

Diabetic ketoacidosis (DKA) in patients with type 1 diabetes mellitus (T1DM) is known to affect memory function, but little is known about its impact on executive function. This study aimed to determine whether a history of DKA was associated with changes in executive function in children with T1DM. The sample consisted of 99 patients with T1DM with histories of DKA, 82 patients with T1DM without DKA, and 100 healthy controls aged 7 to 18 years. Neuropsychological function and emotion assessments were performed in all participants. The Wisconsin Card Sorting Test (WCST) was used to assess executive function. Compared with healthy controls, the DKA group (but not the non-DKA group) had a significantly lower mean intelligence quotient (IQ; p = .006, Cohen d = 0.528) and a significantly higher rate of WCST perseverative errors (p = .006, Cohen d = 0.475). In the DKA group, the age at DKA onset was significantly associated with the IQ (p = .001) and the number of completed WCST categories (p = .046). Higher hemoglobin A1c levels were associated significantly with lower IQ (p < .001), increased rate of WCST perseverative errors (p = .015), and completion of fewer WCST categories (p = .027). DKA has implications for executive function in children with T1DM. These findings emphasize the importance of DKA prevention in patients with known T1DM, especially younger children with newly diagnosed T1DM.

Long-term changes in carbohydrate tolerance, insulin secretion and action in African-American patients with obesity and history of hyperglycemic crises.

IntroductionMany African-Americans (AA) with obesity with newly diagnosed diabetes presenting with diabetic ketoacidosis (DKA) or severe hyperglycemia (SH) discontinue insulin therapy and achieve near-normoglycemia remission (hemoglobin A1c (HbA1c) <7%, fasting blood glucose (FBG) <130 mg/dL) and able to be managed on oral antidiabetic agents (OAD) during follow-up. Using combined data from two randomized controlled trials, we assessed long-term carbohydrate tolerance and changes in insulin sensitivity and insulin secretion.Research design and methodsSeventy-five participants with DKA (n=33) and SH (n=42) underwent 2-hour 75 g oral glucose tolerance test (OGTT) after insulin discontinuation and every 6 months until hyperglycemia relapse (FBG ≥130 mg/dL, HbA1c >7% or two random BG ≥180 mg/dL) while treated with OAD (metformin, sitagliptin or pioglitazone) or placebo. Glucose tolerance status was defined as per the American Diabetes Association. Sensitivity index (Si) was calculated by oral minimal model, insulin secretion as the incremental area under the curve of insulin (IncreAUCi) and disposition index (DI) as Si×IncreAUCi.ResultsDuring remission, OGTT showed normal glucose tolerance (NGT) (n=9 (12%)), prediabetes (n=34 (45%)) and diabetes (n=32 (43%)). DI and Si were higher in patients with NGT versus prediabetes versus diabetes (p<0.001), while IncreAUCi was not significantly different among NGT, prediabetes and diabetes (p=0.14). Achieving NGT status did not prolong near-normoglycemia remission. OAD treatment significantly prolonged hyperglycemia relapse-free survival (log-rank p=0.0012) compared with placebo and was associated with lower hyperglycemia relapse (HR: 0.45, 95% CI: (0.21 to 0.96), p=0.04).ConclusionsIn AA patients with obesity with history of DKA and SH, near-normoglycemia remission is associated with improved insulin secretion and action with half of patients achieving NGT or prediabetes, and only half having diabetes on OGTT. NGT and prediabetes on OGTT were not associated with prolonged hyperglycemia relapse-free survival.Trial registration number NCT01099618, NCT00426413.

A Nonsense GATA6 Mutation Explains History of Congenital Heart Defects and 10 Years of Poorly-Controlled Diabetes Lacking DKA in a Non-Obese 30 Year-Old Incidentally Found to Have Pancreatic Hypoplasia

To report a case of diabetes mellitus (DM) associated with partial pancreatic agenesis and congenital heart disease (CHD) in a patient found to have a nonsense mutation of the GATA6 gene. We present the imaging, laboratory, and genetic findings, and describe the clinical course of a patient with an atypical presentation of DM as well as CHD, who was found to have partial pancreatic agenesis on computed tomography (CT) imaging. Genetic testing was performed to identify monogenic DM. A 30-year-old nonobese female with a waxing and waning pattern of insulin-dependent DM diagnosed at the age of 20 was found to have partial pancreatic agenesis on CT scan. It was unclear whether the patient was experiencing undetected hyperglycemia prior to initial diagnosis of DM. She had no history of diabetic ketoacidosis (DKA) despite poorly-controlled diabetes and years without insulin treatment. The patient also had congenital tricuspid atresia, ventricular septal defect, and transposition of the great vessels with surgical correction in childhood. Partial pancreatic agenesis and CHD with atypical DM prompted genetic testing for monogenic DM, and a nonsense mutation of the GATA6 (c.1242C>A, p.C414*) gene was found. GATA6 mutations are associated with a broad spectrum of diabetic phenotypes, pancreatic agenesis, and a variety of CHDs. This case highlights the importance of considering monogenic diabetes in young, nonobese patients with diabetes, particularly with negative pancreatic antibodies and no history of DKA. Further, this case demonstrates the importance of testing for GATA6 mutations in any young patient with diabetes and CHD.