Sepsis-Induced Diabetic Ketoacidosis (DKA) in Latent Autoimmune Diabetes in Adult (LADA)

Backgrounds. Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes mellitus characterized by older age at diagnosis, presence of pancreatic autoantibodies, and lack of absolute insulin requirement at diagnosis. Patients with LADA had better β-cell function than patients with classic Type 1 DM (T1DM). Overtime, LADA tends to experience rapid and progressive loss of beta cell function that requires intensive insulin therapy. This case report aims to describe a case of Diabetic Ketoacidosis (DKA) in a patient with latent autoimmune diabetes in adult (LADA) induced by sepsis (urinary tract infection/UTI). Case Presentations. A woman, 28 years-old, came to the Emergency Department (ED) RSMH Palembang with chief complaints of decreased consciousness and shortness of breath. Patient had a history of frequent urination, pain when urinating, and fever. Urinalysis examination were glycosuria, proteinuria, hematuria. Hb-A1c level was 10.7%, C-Peptide 0.11 ng/dL, Anti GAD65 qualitative positive, and Islet cell antibody (ICA) negative. Patient was diagnosed with diabetic ketoacidosis (DKA), LADA, and sepsis due to urinary tract infection (UTI). Patients were managed with DKA and sepsis management algorithm. Conclusion. Diabetic ketoacidosis (DKA) in LADA caused by sepsis is an emergency in the metabolic endocrine and diabetes fields. Prompt and appropriate management can improve outcome prognosis in this case.

A Multicenter Survey of Type I Diabetes Mellitus in Chinese Children

PurposeTo investigate the features and treatment status of children with type 1 diabetes mellitus (T1DM) in China.MethodsWe recruited patients <14 years of age with T1DM from 33 medical centers in 25 major cities of China between January 2012 and March 2015. All patients completed a questionnaire that was conducted by their pediatric endocrinologists at all centers.ResultsA total of 1,603 children (755 males and 848 females) with T1DM participated in this survey. Of these, 834 (52.03%) of the patients exhibited diabetic ketoacidosis (DKA) at onset, while 769 patients (47.97%) did not exhibit DKA (non-DKA) at onset. There was a higher proportion of females (55.71%) in the cohort of patients exhibiting DKA at onset than in the non-DKA cohort (49.33%). The mean age of patients exhibiting DKA at presentation was 7.12 ± 0.14 years; this was significantly younger than that in non-DKA group (7.79 ± 0.15 years; P < 0.005). The frequency of DKA in 3 years old, 3-7 years old, and 7 years old or more was 77.21%, 26.17%, and 37.62%, respectively. Upon initial diagnosis, 29.4%, 15.2% and 11.8% of patients showed positivity for glutamic acid decarboxylase antibody (GADA), Insulin autoantibodies (IAA), or islet cell antibody (ICA), respectively. During six months follow-up, 244 patients (15.21%) reported receiving insulin pump therapy, and more than 60% of patients monitored their blood glucose levels less than 35 times per week. Although the majority of patients had no problems with obtaining insulin, 4.74% of the children surveyed were not able to receive insulin due to financial reasons, a shortage of insulin preparations, or the failure of the parents or guardians to acquire the appropriate medicine.ConclusionDKA is more common in very young children. Treatment and follow-up of T1DM in China still face very serious challenges.

Clozapine Induced Insulin Dependence

Background: Antipsychotic medications come with an array of potential side effects in a difficult-to-treat population, particularly if management of other comorbidities is required. A review of the literature shows some studies have discussed the possibility of antipsychotic medication inducing hyperglycemia by blocking pancreatic M3 receptors. Other studies have shown dramatic worsening of metabolic parameters in patients who already have Type 2 Diabetes Mellitus after starting Clozapine. Clinical Case: A 23 year old African American Male with a past history of treatment resistant Schizophrenia presented to the ED with hyperglycemia and altered mental status. Blood sugar 489 mg/dL, anion gap 28 mmol/L, bicarb 13 mmol/L, white Blood Cell count 9.0 x10^3/cmm. Urine positive for Ketones. Chest Xray and EKG were normal, there were no obvious signs of infection. This was the sixth admission for Diabetic Ketoacidosis (DKA) in the past 10 months. Antibodies obtained showed negative Glutamic Acid Decarboxylase Autoantibodies (<5 IU/mL), Islet Cell Antibody IgG, Zinc Transporter 8 Antibody (<10 U/mL), IA-2 (<5.4 U/mL). C-peptide levels were in the low normal range (1.12 ng/mL) with a blood sugar 204 mg/dL. Prior to 10 months ago, the patient did not have a diagnosis of diabetes, with labs showing expected normal fasting blood sugar levels (90s mg/dL) and triglyceride levels of 150 - 200 mg/dL. One month after starting Clozapine for treatment resistant Schizophrenia, A1c doubled to 12.3%, Triglycerides increased to 1,378 mg/dL. The patient had been insulin dependent since the time of starting Clozapine. On this admission, Clozapine was held, DKA resolved with intravenous fluid, potassium replacement, and insulin drip. Repeat testing of c-peptide with blood glucose levels analyzed with the Homeostasis Model Assessment (HOMA) showed increasing HOMA%S (from 93% to 174%) and decreasing HOMA-IR with stopping Clozapine. Psychiatry recommended Clozapine as required treatment of his Schizophrenia, therefore the patient required chronic insulin. Conclusion: This case study shows Clozapine as the only major change in medications or lifestyle in this patient’s case. He demonstrated severe hyperglycemia and development of Diabetes Mellitus within a 4-week period of medication initiation as evidenced by multiple admissions for DKA, with low/normal C-peptide levels and insulin resistance. He has since been managed as a patient with Type 1 Diabetes. Clinicians should take a multidisciplinary approach to clinical surveillance during changes in schizophrenia treatment, particularly with second generation antipsychotics such as Clozapine, with attention to metabolic derangements including DKA.

SAT-686 Type 1 Diabetes Diagnosed in an 83 Year Old Man After Nivolumab Therapy

BACKGROUND Immune checkpoint inhibitors are increasingly being used for a variety of cancers and are a promising treatment option. Immune related adverse effects are their major side effects, most common being hypophysitis and hypothyroidism. While diabetes and adrenalitis have only been rarely reported, these too are becoming more common. We present a case of type 1 diabetes associated with Nivolumab therapy diagnosed in an 83-year-old man. CASE An 83 year old male with past medical history of emphysema, coronary artery disease, hypertension, non-small cell lung cancer treated with lobectomy, hepatitis C cirrhosis with hepatocellular carcinoma with metastasis to lungs, who completed 10 cycles of Nivolumab presented to oncology clinic with complains of polyuria, polydipsia and a weight loss of 10 pounds over the last one week. Lab work showed a blood glucose of 743 with an anion gap of 18 and bicarb of 18. B-hydroxy butyrate was 3.19. He was admitted to our ICU for diabetic ketoacidosis. He did not have a history of diabetes mellitus. No family history of diabetes was reported. His Hemoglobin A1c was found to be 10.1. He had normal blood sugars before starting Nivolumab therapy. His C-peptide was found to be low at 0.61. Insulin antibody, Islet cell antibody, Zinc transporter antibody and GAD antibodies were negative. He was discharged on basal bolus Insulin regimen. He is being followed in our endocrinology clinic and continues to be insulin dependent. CONCLUSION Nivolumab is PD-1 (programmed cell death) inhibitor, which is used as cancer immunotherapy in multiple advanced cancers including hepatocellular carcinoma. Clinically significant endocrinopathies are documented in <5% of patients treated with PD-1 inhibitors. The cause of Diabetes by PD-1 inhibitors is not well defined but believed to be caused by destruction of pancreatic beta cells due to inhibition of autoimmunity by autoreactive T cells. Literature review showed only 42 published cases of PD-1 inhibitor induced type 1 diabetes. Average age at presentation was 62 years and about 69% patients were in DKA at diagnosis. In a recently published study involving 1163 patients who received PD-1 inhibitors, only 21 cases of diabetes were identified, 12 of those were with new onset DM and only 1 case was due to Nivolumab use. Since this type of endocrinopathy is mainly reported in case reports, we will need more research for further understanding of the pathology so that we can keep a watch out for this adverse effect and prevent life- threatening complications.

Differential diagnostic utilities of combined testing for islet cell antibody, glutamic acid decarboxylase antibody, and tyrosine phosphatase antibody

Background. Beta-cell antibody tests are used for the differential diagnosis of diabetes mellitus. They permit to discriminate between the type 1 diabetes (T1D) and non-autoimmune diabetes types. To choose an appropriate test for ruling in or ruling out the T1D a physician needs to know how conclusive test results are. The most powerful estimate of test conclusiveness is its likelihood ratio (LHR). The higher LHR of a positive result (LHR+), the more posttest probability of T1D; the lower LHR of a negative result (LHR), the less posttest probability of T1D. Aims. To compare conclusiveness of single and combined tests for antibodies to islet cells (ICA), glutamate decarboxylase (GADA), and tyrosine phosphatase IA-2 (IA-2A), and to evaluate posttest probabilities of T1D at various pretest probabilities. Methods. All antibodies were tested in parallel in 169 children and adolescents with a new-onset T1D, and in 169 persons without this disease. ICA, GADA, and IA-2A were determined by indirect immunofluorescence, radioimmune assay, and ELISA, respectively. LHR+ and LHR were calculated with the MedCalc Statistical Software. Posttest T1D probabilities were calculated from Bayes theorem-based equation. Results. Among single tests, an ICA test had the greatest LHR+ and the smallest LHR, and consequently was the most reliable either for ruling in or ruling out the T1D. Among test combinations, an ICAGADA combination had the greatest LHR+ and was the most suitable for T1D confirmation. The triple combination ICAGADAIA-2A had the smallest LHR and was the most suitable for T1D exclusion. Conclusions. In the differential diagnosis of diabetes, the most appropriate test for ruling in the T1D is the double combination ICAGADA. With both antibodies positive, this combination provides the highest posttest T1D probabilities at any pretest probability. The most appropriate test for ruling out the T1D is the triple combination ICAGADAIA-2A. With all three antibodies negative, this combination provides the lowest posttest T1D probabilities.

Factors associated with increased irisin levels in the type 1 diabetes mellitus

Objective. The aim of the present study was to determine the irisin levels in patients with the type 1 diabetes mellitus (T1DM) and to examine the relation of irisin levels with the inflammation and autoimmunity.Methods. This study included 35 cases diagnosed with T1DM and 36 healthy volunteers. Antiglutamic acid decarboxylase (anti-GAD), islet cell antibody (ICA), and insulin autoantibody levels were measured in patients at the time when they were included into the study and recorded from the patient files. Serum irisin levels were measured by ELISA kit.Results. The median irisin levels were determined higher in T1DM group compared to the control one (6.8 ng/ml vs. 4.8 ng/ml, p=0.022; respectively). Median irisin levels were higher in anti-GAD (p=0.022) and ICA (p=0.044) positive groups compared to negative groups. In T1DM group, irisin levels displayed positive correlation with glycosylated hemoglobin (HbA1c) (r=0.377, p<0.001) and anti-GAD (r=0.392, p=0.020) and negative correlation with creatinine (r=-0390, p=0.021). In multivariate regression model, HbA1c (B±SE: 2.76±17683, p<0.001), and anti-GAD (B±SE: 2.311±0.610, p=0.001) were determined as independent predictors for predicting the irisin levels.Conclusion. In patients with T1DM, which chronic inflammation and autoimmunity take part in their etiopathogenesis, anti-GAD levels were an independent risk factor for the irisin. Th is may suggest that factors such as inflammation and autoimmunity can be effective in the synthesis of irisin.