Onset Of Type Research Articles

Malnutrition at diagnosis in amyotrophic lateral sclerosis (als) and its influence on survival: Using glim criteria.

Malnutrition is a prognostic factor in Amyotrophic Lateral Sclerosis (ALS). Sometimes, this condition is underdiagnosed, and it might influence on disease progression. To evaluate a) nutritional status at the beginning of specialized nutritional treatment and b) the influence of initial nutritional status on disease evolution and survival in a group of patients with amyotrophic lateral sclerosis (ALS). An interhospital registry of patients with motor neuron disease treated at the Clinical Nutrition Clinics of six hospitals in the region of Castilla y León in Spain was created. The study was developed from January 2015 to December 2017. An anamnesis, affiliation data, past medical history, disease evolution, nutritional history and an anthropometry and bioelectrical impedance analysis were performed at baseline. The mortality rate was compared among those patients with worse nutritional status at the beginning of the follow-up against those with a better nutritional situation using two tools: The Subjective Global Assessment (SGA) and the criteria of the Global Leadership Initiative for Malnutrition (GLIM). A total of 93 patients were analysed. The median age of the patients was 67 (57.5-75.5) years. The median Body Mass Index was 24.4 (21.7-25.9) kg/m2 and the median percentage of weight loss was 9.32 (2.7-17.6)% without differences between the onset type. According to the SGA, 27 (29%) patients were in grade A; 43 (46.3%) patients were in grade B and 23 (24.7%) were in grade C. According to the new GLIM malnutrition criteria, 45 patients (48.4%) had malnutrition. Patients with worse nutritional status had a lower survival median with both SGA (SGA A: 20.5 (10.2-35) months vs SGA B-C: 12 (5.2-23.7) months (p=0.03)) or the new GLIM criteria according to severity (severe malnutrition: 18 (5-24) months vs. no severe malnutrition: 20 (12-33) months (p=0.01)). In the multivariate analysis, malnutrition measured by SGA was an independent risk factor (HR: 4.6 (1.5-13.9) p=0.007) for survival over 15 months when adjusted for age, sex and type of onset of ALS. Patients with ALS have a severe deterioration in nutritional status when analysed using a classical malnutrition test (SGA) or a new one (GLIM criteria). Patients with a better nutritional situation according to SGA and GLIM severity classification were associated with a longer survival time.

Time-varying and dose-dependent effect of long-term statin use on risk of type 2 diabetes: a retrospective cohort study

BackgroundWe evaluated the effect of statin use on new-onset type 2 diabetes among individuals without atherosclerotic cardiovascular disease (ASCVD) using nationally representative South Korean claims data (2002–2013, N = 1,016,820).MethodsA total of 13,698 patients (statin users 5273, non-statin users 5273) aged 40–74 years, newly diagnosed with dyslipidemia but without any history of diabetes or ASCVD, were selected in 2005. We followed up the final sample until 2013 and evaluated the cumulative incidence of type 2 diabetes. We used extended Cox regression models to estimate the time-varying adjusted hazard ratios of statin use on new-onset type 2 diabetes. We performed further analyses based on the cumulative defined daily dose of statin received per year to evaluate the degree of risk compared to non-statin users.ResultsOver the mean follow-up period of 7.1 years, 3034 patients developed type 2 diabetes; the number of statin users exceeded that of non-users, demonstrating that statin use significantly increased the risk of new-onset type 2 diabetes. The risk of new-onset type 2 diabetes differed among statin users according to cDDD per year (adjusted HR = 1.31 [95% CI 1.18–1.46] for less than 30 cDDD per year; 1.58 [1.43–1.75] for 30–120 cDDD per year; 1.83 [1.62–2.08] for 120–180 cDDD per year; and 2.83 [2.51–3.19] for more than 180 cDDD per year). The diabetogenic effect of pitavastatin was not statistically significant, but the risk was the largest for atorvastatin. Long-term exposure (≥ 5 years) to statins was associated with a statistically significant increase in the risk of new onset type 2 diabetes in all statin subtypes explored, with the highest magnitude for simvastatin (HR = 1.916, 95% CI 1.647–2.228) followed by atorvastatin (HR = 1.830, 95% CI 1.487–2.252).ConclusionsStatin use was significantly associated with an increased risk of new-onset type 2 diabetes. We also found a dose–response relationship in terms of statin use duration and dose maintenance. Periodic screening and monitoring for incident type 2 diabetes may be warranted in long-term statin users.

Associations of diabetes severity and risk of depression: a population-based cohort study

ObjectivePrevious literature investigating effects of diabetes complications on subsequent depression have been inconsistent. We aim to investigate associations of diabetes, complication severity, and depression. DesignThis study used a nationwide database to establish an 11-year cohort comprised of people with new onset Type II diabetes mellitus (DM) aged 20 and above. MethodSeverity of DM was measured using the adapted Diabetes Complication Severity Index (aDCSI). Status of depression was determined by having one recorded depression diagnosis from the inpatient setting or three recorded depression diagnoses from the outpatient setting. The risk of depression was analyzed by multivariate Cox proportional models. ResultsIn 50,590 cases with new onset DM from years 2000 to 2011, the incidence of depression increased with severity and rates of progressions in diabetes complications regardless of demographic status, comorbidities, or medication compliance. Adjusted hazard ratios (aHR) of depression were 1.21, 1.25, 1.48 (p<0.001 for trend) in patients with a total aDCSI score of 1, 2, and > 3, respectively. Risks of depression were the highest in subgroup with the most serious progression (change of aDCSI score >2 per year) (aHR ranged between 11.6~26.0). Elevated risks of depression (aHR: 1.59~4.36) were also observed in the slower progression subgroups throughout the disease course. ConclusionsRisks of depression were associated with multiple DM-related complications and rates of progression in severity.

SAT-678 New Onset Type 1 Diabetes and Immune Thrombocytopenic Purpura in an Adolescent Male: A Case Report

INTRODUCTION:Type 1 diabetes mellitus (T1D) is an autoimmune condition caused by anti-pancreatic antibodies which attack and destroy the insulin-producing beta cells. Similarly, in immune thrombocytopenic purpura (ITP), anti-platelet antibodies destroy platelets, causing low platelet counts which can lead to petechiae and bleeding. Common autoimmune conditions seen in children with T1D include thyroid and celiac disease. Previous case reports discussed ITP in children with known T1D. Our patient presented with new onset T1D and diabetic ketoacidosis (DKA) in addition to new onset ITP.CLINICAL CASE:The patient is a 12 year old previously healthy male with a several week history of polyuria, polydipsia and nocturia, in addition to fatigue and lack of weight gain in the previous two years. Initial labs confirmed diagnosis of T1D with hemoglobin A1c of 12.9% and serum glucose of 460 mg/dL, in addition to DKA, with bicarbonate of 13 mmol/L, pH of 7.30, elevated anion gap and beta-hydroxybutyrate. Due to the presence of DKA, the patient was started on an insulin drip. Thyroid labs showed hyperthyroidism, with TSH- <0.02 (0.5-4.5 mIU/L) and free T4- 2.84 (0.7-1.68 ng/dL), so he was started on methimazole 20 mg daily. Confirmatory pancreatic antibodies and thyroid antibodies were sent. CBC showed thrombocytopenia with initial platelet count of 41,000, hemoglobin of 16.9 g/dL, and white blood cells of 5.05. Follow up platelets continued low at 37,000, so he was seen by a hematologist, which confirmed the Diagnosisx of ITP. Patient had a history of easy bruising in arms and legs, one episode of epistaxis and minimal bleeding after brushing teeth, with negative history of hematuria. Follow up labs resulted in negative thyroid antibodies (TPO Ab, TSI and thyroglobulin Ab) with normalization of labsthyroid function tests, so the methimazole was discontinued. Patient is being followed by Hematologya hematologist, and pancreatic antibodies were done, which were negative. Hematology concurred with diagnosis of ITP despite negative antibodies due to diagnosis of T1D. First line therapy for ITP is IVIG and steroids, however due to national shortage of IVIG and risk for worsening hyperglycemia with steroids, these were avoided. Instead, patient was started on Eltrombopag daily for treatment of his ITP. Platelet count has improved on eltrombopag, with latest range of 126-146,000. Latest hemoglobin A1c is of 6.2%.CONCLUSION:In the case of new onset type 1 diabetes mellitusT1D, it is’s important to keep in mind that ITP is another autoimmune condition that can present in these patientspresent. In addition to IVIG and steroids, Eltrombopag is a good ttreatment option that does not interfere with glycemic control. More research is needed to measure the frequency of ITP among patients with type 1 diabetes.

SAT-665 A Case of Hyperglycemia in Post Pancreas Transplant Patient-Is It Insulin Deficiency or Insulin Resistance

IntroductionPancreatic transplant (PTx) is a less commonly utilized option for patients with Type 1 Diabetes (DM1), usually with co-morbid end stage renal disease. Hyperglycemia in the post-PTx population can be multifactorial. We report a case of hyperglycemia with ketosis in a post-PTx patient due to insulin resistance and relative insulin deficiency.Case Presentation55-year-old male patient with DM1 who underwent simultaneous kidney-PTx. His immunosuppressant (IS) medications were tacrolimus, mycophenolate and prednisone. Tacrolimus levels were therapeutic and his transplant course was benign. He did not require insulin or other glucose-lowering medications post-PTx for 29 years. However, during evaluation for subacute illness with his PCP, he was found to have HbA1c of 12.6%, plasma glucose (PG) 776 mg/dl, and positive urine ketones. He was started on insulin degludec 24 units daily, which was quickly tapered to 8 units daily due to hypoglycemia. OGTT showed fasting PG of 93 mg/dl, 2-hour PG of 115 mg/dl, and stimulated C-peptide of 7.5 ng/ml. HbA1c improved to 7.4% after being on insulin for 1 month. Insulin degludec was tapered and discontinued within 2 months due to hypoglycemia despite low doses and robust PTx function. Home blood glucoses (BG) were controlled and HbA1c stable at 6% off insulin therapy. Eighteen months later, he was hospitalized for hyperglycemia with ketosis, without acidosis, during an upper respiratory infection. He was restarted on insulin (glargine, aspart). Once the acute stress resolved, his insulin dose needs reduced significantly, tapering down to insulin glargine 5 units daily. Along with daily home BG monitoring, HbA1c and C-peptide are performed every 3 months, with recent HbA1c 5.2% and C-peptide 3.0 ng/ml (simultaneous PG of 103 mg/dl).DiscussionCauses of post-PTx hyperglycemia include graft failure due to acute or chronic rejection, insulin resistance, beta cell dysfunction due to IS medications, pancreatitis, or, rarely, recurrence of autoimmunity. Factors predicting hyperglycemia are pre-PTx insulin dose, BMI and acute rejection. New onset type 2 diabetes can occur due to insulin resistance from IS medications and genetic predisposition. Measurement of C-peptide after OGTT can help determine the cause. Insulin is the standard treatment even with detectable C-peptide, though oral glucose-lowering medications have been used in the setting of insulin resistance. In this patient, severe hyperglycemia occurred during stress. He had very low insulin dose requirements when the stress and hyperglycemia resolved and reasonable C-peptide values. This scenario was most consistent with hyperglycemia due to insulin resistance and subsequent relative insulin deficiency during stress, with continued PTx function. This illustrates the importance of detailed assessment and personalized treatment in patients with post-PTx hyperglycemia.

SAT-667 Partial Beta-Cell Destruction: An Atypical Case of Immune Checkpoint Inhibitor Diabetes Mellitus

Background: Autoimmune diabetes mellitus (CPI-DM) caused by immune checkpoint inhibitors (CPIs) is rare- occurring in approximately one percent of patients exposed to this form of cancer immunotherapy. Typically, this immune related adverse event occurs after treatment with PD-1/PD-L1 inhibitors. It is characterized by abrupt insulinopenia leading to acute hyperglycemia. Beta cell autoantibodies are positive in approximately half the cases. DKA is common at the time of diagnosis. Recovery of beta cell function has been reported in only two case reports. In one case, spontaneous resolution occurred following cessation of CPI therapy and in the other the patient was treated with infliximab for concurrent inflammatory arthritis prior to resolution of CPI-DM. Clinical Case: A 50-year-old woman was started on adjuvant pembrolizumab for stage IIIC melanoma following surgery. She had no prior history of diabetes mellitus, thyroid disease, or other autoimmune disease. Pre-infusion random blood glucoses (RBG) were 84 - 105 mg/dL. After 36 weeks, she developed hypothyroidism (TSH 17.5 (0.5-4.1 mIU/L), FT4 6 (10-18 ug/dL)) and started levothyroxine. Pembrolizumab was continued. For nine weeks following her diagnosis with CPI- hypothyroidism, her pre-infusion RBG ranged from 102-133. At 45 weeks (15 cycles) after initiating pembrolizumab, her RBG was 260. She was not on glucocorticoids and had no other signs of inflammation or stress. Pembrolizumab was continued. Just prior to her 17th cycle, 48 weeks after initiating adjuvant pembrolizumab, her RBG was 482 with a normal anion gap and HCO3, and her A1c was 8.9%. Her last dose of pembrolizumab was held. She started metformin and liraglutide. In just three weeks, a random c-peptide was inadequate at 1.7 (0.8-3.5 ng/mL) with a recent RBG of 220 and A1c of 10.3%, showing the acuity and extremity of her hyperglycemia. Over the course of the year, she has achieved excellent glucose control (A1c 6.3-7.1) on this regimen with preservation of insulin production (c-peptides 1.4-1.8 with matched RBG 92-129). She never required insulin. Her beta cell autoantibodies are negative. Clinical Lessons: This is a case of CPI-DM in which the patient did not have complete loss of beta-cell function. The acuity of her hyperglycemia is not consistent with new onset type 2 diabetes. At diagnosis, her c-peptide was inadequate suggesting insufficient insulin production rather than insulin resistance. Therefore, her hyperglycemia is more consistent with CPI-DM than type 2 diabetes. Atypically, she did not progress to fulminant beta cell failure, which could have been due to cessation of pembrolizumab (which is not unique to this case), initiation of liraglutide and metformin, or other unknown immunologic responses that inhibited full beta cell loss. This case raises the possibility of preventing fully insulin dependent CPI-DM if hyperglycemia is caught and treated early.

SAT-181 Pheochromocytoma Masquerading as Acute Coronary Syndrome. To Cath or Not to Cath?

BackgroundPheochromocytoma had been known as the “Great Mimic” as it can present with signs and symptoms consistent with numerous differentials [1]. Cardiac ischemia is one in particular which creates a diagnostic dilemma and poses significant risk for misdiagnosis.Clinical Case62-year-old female with recent onset hypertension and type II diabetes(HbA1C of 6.9%) presented to the ER with new episodes of nausea, vomiting, and substernal chest pain. During the preceding four months she also experienced episodic headaches, palpitations, and flushing.Initial vital signs were significant for blood pressure 157/81 mm Hg. Physical exam was unremarkable. An Electrocardiogram showed normal sinus rhythm with right axis deviation and ST segment depressions in the inferior leads II, III and aVF.Labs revealed a troponin peak at 2.95 (<0.04 ng/mL) and d-dimer of 403 (<400 ng/mL). Serum chemistry, TSH, and complete blood count were within normal limits. A CT Chest with angiography was negative for pulmonary emboli. However, it did note a heterogenous 7.6 cm right adrenal mass. At this juncture there was clinical concern for pheochromocytoma and serum free metanephrines was ordered.Prior to receiving medical treatment for her pheochromocytoma, she underwent cardiac catheterization which showed no evidence of coronary artery disease. The procedure was uncomplicated. However, post-procedurally she did develop worsening paroxysms and severe hypertensive episodes with heart rate up to 140 beats per minute and systolic blood pressure up to 220 mm Hg. She was subsequently started on alpha blockage with phenoxybenzamine 10mg twice daily to which she responded favorably. Her initial serum free metanephrine was 6087(< 57 pg/mL) and free normetanephrine 2489 (<148 pg/mL).ConclusionsThis case highlights the importance of maintaining a high index of suspicion for pheochromocytoma for all patients with acute chest pain and hypertension. Her untreated pheochromocytoma could have been fatal during or immediately after the cardiac catheterization. Given the suspicion for pheochromocytoma in this case, it would have been most appropriate to have begun alpha blockade after blood was drawn for metanephrines and before attempting any invasive procedures. Pheochromocytoma should be included in the differential diagnosis of acute coronary syndrome because it can mimic an ischemic episode.

SAT-673 Acute Onset Type 1 Diabetes Mellitus Caused by the Checkpoint Inhibitor Nivolumab

Background. Checkpoint inhibitors are monoclonal antibodies that augment immune system antitumor activity. Nivolumab is a checkpoint inhibitor that targets the programmed cell death receptor 1 (PD-1). Approximately 15% of patients treated with checkpoint inhibitors experience endocrine immune-related adverse events (irAEs), with autoimmune thyroid disorders and hypophysitis the most common endocrine irAEs. We present a case of acute onset type 1 diabetes mellitus (T1D) complicating treatment with nivolumab. Case. An 84 year old female received nivolumab (Opdivo) for metastatic small cell lung cancer. She tolerated twelve cycles of treatment well, but after the thirteenth cycle, she developed polydipsia and polyuria that prompted her to seek medical attention. Laboratories in the emergency department were notable for plasma glucose 998 mg/dL, bicarbonate 13 mM, anion gap 24, and strongly positive serum and urine ketones. An insulin infusion and parenteral fluids promptly resolved diabetic ketoacidosis (DKA), and the patient was then managed with subcutaneous basal/bolus insulin. Antibody markers (e.g. anti-GAD65) for T1D were undetectable, and evaluation for other endocrine irAEs was unremarkable. Given the rapid onset of DKA and the patient’s advanced age, she was diagnosed with nivolumab-induced T1D and discharged home on exogenous insulin. Conclusions. In a recent meta-analysis of 38 immune checkpoint inhibitor trials and over 7,500 patients, T1D was the least common endocrine irAE. The incidence of T1D was 0.2% compared to 6.6% for hypothyroidism, 2.9% for hyperthyroidism, 1.3% for hypophysitis, and 0.7% for primary adrenal insufficiency. All but one case (12/13) of T1D occurred in patients treated with a PD-1 inhibitor. Markers of both cellular and humoral diabetes-associated autoimmunity have been demonstrated in patients with T1D during treatment with nivolumab, and autoimmune destruction of beta-cells is the presumed etiology of diabetes. However, diabetes autoantibodies are detected in only about 50% of cases, and the absence of humoral markers does not exclude the diagnosis of nivolumab-induced T1D. There is a slight male predominance among published cases of nivolumab-induced T1D, and though median onset of T1D1 is after 11 weeks of treatment, there is a wide range of recorded times to T1D onset. Approximately 70% of patients present in DKA, and the significant majority of patients have undetectable or low C-peptide levels. Unfortunately, loss of beta-cell function persists after stopping nivolumab, and lifelong exogenous insulin is required for diabetes management. Though nivolumab-induced T1D is rare, the high risk of DKA as in this patient’s case illustrates the importance of recognizing nivolumab as a potential cause of autoimmune diabetes in older patients receiving anti-PD-1 immunotherapy.

SUN-090 Investigation of Imprinting Defects in MKRN3 and DLK1 in Children with Idiopathic Central Precocious Puberty Through Specific DNA Methylation Analysis

Background: Loss of imprinting has been implicated in the pathogenesis of several human diseases. Monogenic causes of central precocious puberty (CPP) were identified in families with loss-of-function mutations affecting mainly the coding region of two paternally expressed imprinted genes: Makorin ring finger 3 (MKRN3) and Delta-like 1 homolog (DLK1). The role of imprinting defects involving these two genes in CPP has not been described so far.Objective: To investigate the methylation status at primary differentially methylated regions (DMR) of MKRN3 and DLK1 in a cohort of children with idiopathic CPP.Patients and methods: One-hundred and twenty CPP patients (112 sporadic, 8 familial; 115 females, 5 males) were selected for analysis. Leukocyte DNA was obtained from all patients. MKRN3 and DLK1 pathogenic allelic variants were first excluded by DNA sequencing analysis. Bisulfite treatment followed by Allele-Specific Methylated Multiplex Real-Time Quantitative PCR was performed with leukocyte DNA, analyzing separately the methylation index (MI) of MKRN3:TSS-DMR and DLK1/MEG3:IG-DMR for each patient. The MI results were compared with controls with normal pubertal development.Results: Mean age at puberty onset was 5.8 ±1.9yr for girls and 7.2 ±2.6yr for boys. Hypomethylation at DLK1/MEG3:IG-DMR was identified in 3 patients (I, II and III) with sporadic CPP: MI 10%, 16% and 11%, respectively. Interestingly, cases II and III were both girls who had been firstly referred to pediatric endocrinology for presenting precocious menarche; while case I was a boy who had been referred for presenting mild growth retardation, and developed CPP during monitoring. In addition, during follow-up, other clinical findings were noticed: being born small for gestational age, prominent forehead, small hands/feet, overweight/obesity and early onset type 2 diabetes in case III. Additional genetic investigation included SNP array in cases I and II, identifying a maternal uniparental disomy at chromosome 14 (upd(14)mat). Meanwhile, case III had normal genomic microarray and microsatellites analysis, excluding copy number variants and upd(14)mat, and indicating a mechanism of epimutation at DLK1/MEG3:IG-DMR. Uniparental disomy and epimutation are molecular mechanisms associated with the imprinting disorder known as Temple syndrome. In the remaining cases, mean MI for DLK1/MEG3:IG-DMR was 49±2%. In all cases, mean MI for MKRN3:TSS-DMR was 49±6%. There were no significant correlations between age at puberty onset and MI for MKRN3 (p=0.69) and DLK1(p=0.45).Conclusion: There was no leukocyte DNA methylation defect at MKRN3 imprinting control region in the idiopathic CPP cohort. DLK1/MEG3:IG-DMR hypomethylation was identified in 3 patients with CPP and additional findings of Temple syndrome, indicating that loss of effective imprinting of DLK1 locus is a mechanism leading to CPP.

Reduced level of CX3CR1 positive T-cells and monocytes in children with, newly diagnosed, Type 1 diabetes

Abstract Background The chemokine CX3CL1 is associated with many autoimmune diseases. Type 1 diabetes (T1D) is an autoimmune disease characterized by an insufficient insulin production due to T-cells mediated destruction of pancreatic beta cells. CX3CL1/CX3CR1 plays an important role in recruitment and extravasation of T-cells and monocytes to the inflammatory site. Aim To investigate the role of CX3CL1 and its receptor CX3CR1 in children with T1D in acute phase (day 0), 10 days and 3 months after treatment compared to healthy subjects (HS). Methods Blood samples from children (range 2–18 years) with new onset type 1 diabetes (day 0 (n=14), day 10 (n=9) and 3 month (n=14)) and 24 age matched HS was collected. The concentrations of CX3CL1 in plasma (T1D day 0, day 10 and HS) was measured by ELISA. Receptor expression of CX3CR1 on monocytes and T-cells was analyzed by flow cytometry. Results The study showed significant higher concentrations of CX3CL1 in serum from T1D day 0 compared to HS (p&amp;lt;0.05) and T1D day 10 (p&amp;lt;0.01). No significant difference was observed between T1D at day 10 and HS. Furthermore, the level of CX3CR1 positive T-cells was significantly lower in T-cells from T1D day 0 compared to HS (p&amp;lt;0.003) and T1D 3 months (p&amp;lt;0.007). In addition, the amount CX3CR1 positive monocytes were significant lower in T1D day 0 compared to HS (p&amp;lt;0.003). Conclusion The low amount of CX3CR1 positive T-cells and monocytes in peripheral circulation in acute phase T1D, despite the high level of s-CX3CL1, indicate that the T-cells and monocytes might have transmigrated to the inflammatory site. This study indicates that CX3CL1/CX3CR1 axis could play a role in the pathogenesis of T1D.

Abstract #806967: Screening for Adult Onset Type 1 Diabetes (T1D) with Only Glutamic Acid Decarboxylase (GAD65) and Ica (Islet Cell Antibodies) will Lead to a Missed Diagnosis and Inappropriate Therapy in a Significant Percentage of Patients

Abstract #806967: Screening for Adult Onset Type 1 Diabetes (T1D) with Only Glutamic Acid Decarboxylase (GAD65) and Ica (Islet Cell Antibodies) will Lead to a Missed Diagnosis and Inappropriate Therapy in a Significant Percentage of Patients

Diabetes mellitus exacerbates citrin deficiency via glucose toxicity

AimsCitrin is an aspartate/glutamate carrier that composes the malate-aspartate reduced nicotinamide adenine dinucleotide (NADH) shuttle in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), failure to thrive and dyslipidemia (FTTDCD) and adult–onset type II citrullinemia (CTLN2). Hepatic glycolysis is essentially impaired in citrin deficiency and a low-carbohydrate diet was recommended. The lethal effect of infusion of glycerol- and fructose-containing osmotic agents was reported in these patients. Hyperalimentation was also reported to exacerbate CTLN2; however, glucose toxicity was unclear in citrin deficiency. MethodsWe studied two CTLN2 patients complicated with type 2 diabetes mellitus (DM), Case 1 presented with hyperammonemic encephalopathy accompanied with DM, while Case 2 presented with hyperammonemic encephalopathy relapse upon the onset of DM after several years’ remission following supplementation with medium-chain triglycerides (MCT) and adherence to a low-carbohydrate diet. ResultsInsulin therapy with MCT supplementation and a low-carbohydrate diet improved hyperammonemia and liver function in Case 1. Additional insulin therapy improved hyperammonemia in Case 2. ConclusionGlucose is not toxic for citrin deficiency in normoglycemia because glucose uptake and metabolism by hepatocytes are limited in normoglycemia. However, glucose becomes toxic during persistent hyperglycemia and antidiabetic therapy is indispensable for CTLN2 patients with DM.

Statins are associated with new onset type 2 diabetes mellitus (T2DM) in Medicare patients ≥65 years.

To evaluate the association of statins and co-morbidities with new onset type 2 diabetes mellitus (T2DM) in patients 65 years and older. This retrospective study used de-identified administrative healthcare claims and enrolment data from a Medicare Advantage Prescription Drug (MAPD) health plan offered by a large multistate healthcare company. The plan covered >2.4 million individuals, of whom >1.7 million individuals were ≥65 years. Of these, 265 554 individuals had continuous MAPD enrolment January 2008 to December 2015. The unadjusted model assessed demographic, pharmacy and T2DM co-morbidities as covariates. Significant variables (P < .05) in the unadjusted model were then included in the adjusted model. The adjusted model used Cox proportional hazards to evaluate covariate effects. Matched propensity score analysis was used to analyse the association of statins and T2DM onset. The cumulative rate of diagnosed T2DM onset in the study cohort was 4.82% (4314/89 390). Annualised incidence of T2DM diagnosis was 0.82%, 0.88%, 1.04% and 2.09% in 2012, 2013, 2014 and 2015, respectively. T2DM onset was associated with male sex, non-white (African American or Hispanic ethnicity), statin use, hypertension, hyperlipidaemia, heart failure, lower limb ulceration, atherosclerosis, other retinopathy, angina pectoris, poor vision and blindness and absence ischaemic heart disease (IHD). Matched propensity score analysis showed that statin use was significantly associated with T2DM onset (Odds Ratio = 1.26, 95% Confidence Interval: 1.12-1.41, P < .0001) in the adjusted model. Analyses indicated that statin usage was associated with new onset T2DM after adjusting for covariates.

Diagnostic journey in Spinal Muscular Atrophy: Is it still an odyssey?

BackgroundThe advent of new therapies has increased the need to achieve early diagnosis in Spinal Muscular Atrophy (SMA). The aim of the present study was to define the age of diagnosis in the three main types of SMA with pediatric-onset and the timing between the recognition of clinical signs and confirmed genetic diagnosis.MethodsAll patients with a confirmed diagnosis of type I, II, III SMA followed in 5 Italian centers were included in this study, assessing age at symptoms onset, presenting sign or symptom, age at diagnosis, interval between clinical onset and diagnosis and type of medical investigations conducted in order to obtain the diagnosis.ResultsThe cohort included 480 patients, 191 affected by SMA type I, 210 by type II and 79 by type III. The mean age at diagnosis was 4.70 months (SD ±2.82) in type I, 15.6 months (SD±5.88) in type II, and 4.34 years (SD±4.01) in type III.The mean time between symptom onset and diagnosis was 1.94 months (SD±1.84) in type I, 5.28 months (SD±4.68) in type II and 16.8 months (SD±18.72) in type III.ConclusionsOur results suggest that despite improved care recommendations there is still a marked diagnostic delay, especially in type III. At the time new therapies are becoming available more attention should be devoted to reducing such delay as there is consistent evidence of the benefit of early treatment.

Serum 1,5-Anhydroglucitol to Glycated Albumin Ratio Can Help Early Distinguish Fulminant Type 1 Diabetes Mellitus from Newly Onset Type 1A Diabetes Mellitus.

Background Fulminant type 1 diabetes mellitus (FT1DM) onsets abruptly and usually occurs within 1 week after the onset of hyperglycemic symptoms. Glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) are indicators that reflect short-term glucose levels. This study was aimed at investigating whether the 1,5-AG/GA index (AGI) is a suitable indicator for early FT1DM identification. Methods A total of 226 subjects were enrolled, all with glycated hemoglobin A1c (HbA1c) < 8.7%. FT1DM was diagnosed based on the 2012 Japan Diabetes Society criteria. Results The AGI level was 0.54 (0.17–1.36) in the whole group. It was lower in FT1DM patients (0.16 [0.10–0.25]). Among the participants whose HbA1c did not exceed 7.0%, the AGI of FT1DM decreased significantly compared to type 1A diabetes (T1ADM) and latent autoimmune diabetes in adults (LADA) patients (0.16 [0.12–0.26] vs. 0.46 [0.24–0.72] vs. 0.46 [0.24–0.72] P < 0.05). The receiver operating characteristic (ROC) curve showed that AGI can be used to distinguish FT1DM and T1ADM patients with HbA1c < 8.7%. Diagnosing FT1DM based on AGI ≤ 0.3 only can help narrow down suspected FT1DM by up to 26.87%. If we diagnosed FT1DM when AGI was ≤0.3 and HbA1c was ≤7.0%, the success rate further increased to 86.57%, among which 85.00% of FT1DM and 87.23% of T1ADM patients were successfully identified. Therefore, using the combination criteria of AGI and HbA1c would improve the differential diagnosis efficacy by 61.11% compared with the AGI criterion only. Conclusion AGI can help facilitate the early differential diagnosis of FT1DM and T1ADM when HbA1c < 8.7%, with an optimal cut-off point of 0.3.

High-parametric evaluation of human invariant natural killer T cells to delineate heterogeneity in allo- and autoimmunity

AbstractHuman invariant natural killer T (iNKT) cells are a rare innate-like lymphocyte population that recognizes glycolipids presented on CD1d. Studies in mice have shown that these cells are heterogeneous and are capable of enacting diverse functions, and the composition of iNKT cell subsets can alter disease outcomes. In contrast, far less is known about how heterogeneity in human iNKT cells relates to disease. To address this, we used a high-dimensional, data-driven approach to devise a framework for parsing human iNKT heterogeneity. Our data revealed novel and previously described iNKT cell phenotypes with distinct functions. In particular, we found 2 phenotypes of interest: (1) a population with T helper 1 function that was increased with iNKT activation characterized by HLA-II+CD161– expression, and (2) a population with enhanced cytotoxic function characterized by CD4–CD94+ expression. These populations correlate with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation and with new onset type 1 diabetes, respectively. Our study identifies human iNKT cell phenotypes associated with human disease that could aid in the development of biomarkers or therapeutics targeting iNKT cells.

Higher patient assessed quality of chronic care is associated with lower diabetes distress among adults with early-onset type 2 diabetes: Cross-sectional survey results from the Danish DD2-study

AimAmong adults aged 20–45 years with type 2 diabetes mellitus, we examined the perceived quality of chronic care, and its associations with (i) sociodemographic and clinical characteristics, and (ii) diabetes distress. MethodsIn total, 216/460 (47%) completed a self-administered survey assessing sociodemographic characteristics, patient assessed chronic illness care (PACIC-20, scale of 1–5) and diabetes distress (PAID-20, scale of 0–100), and 197 had full quality of care data for assessment. We obtained clinical data from national registers and used linear and logistic regression models to examine associations. ResultsThe mean (SD) PACIC score was 2.6 (0.9) (score range 1–5). Lower PACIC scores were associated with female sex and current unemployment, and with receiving diabetes care in general practice compared with hospital outpatient clinics [mean difference: −0.4 (95% confidence interval (CI) (−0.7 to −0.2)]. People with upper quartile PACIC scores were less likely to report high diabetes distress compared with people with lower quartile PACIC scores [odds Ratio 0.3 95%CI (0.1–0.8)]. ConclusionHigher quality of care was associated with lower diabetes distress among adults with early onset type 2 diabetes mellitus, but respondents reported less than optimal quality in several core areas of chronic care.

Lipoprotein insulin resistance score and branched-chain amino acids increase after adrenalectomy for unilateral aldosterone-producing adenoma: a preliminary study

Background and aimsPrimary aldosteronism (PA) due to unilateral aldosterone-producing adenoma (APA) is preferentially treated by unilateral adrenalectomy (ADX), but little is known about the changes in lipid and glucose metabolism that may occur after ADX.MethodsWe studied 19 non-diabetic patients who did not use lipid-lowering drugs with PA due to APA before and 6 months after unilateral ADX. Fasting plasma lipids, lipoprotein subfractions, branched-chain amino acids (BCAA), and GlycA, a pro-inflammatory glycoprotein biomarker, were measured by nuclear magnetic resonance (NMR) spectroscopy. The Lipoprotein Insulin Resistance (LP-IR) score, which is based on six lipoprotein variables, was calculated.ResultsIn all patients, hyperaldosteronism was resolved after ADX. Body mass index and fasting plasma glucose were unchanged, but HbA1c increased (p = 0.002). Plasma triglycerides, large triglyceride-rich lipoprotein (TRL) cholesterol, and large TRL particles were increased (p < 0.01), resulting in an increase in TRL size (p = 0.027). High-density lipoprotein size was decreased (p = 0.015). LP-IR scores (p = 0.001) and total BCAA (p = 0.017) were increased, but GlycA remained unaltered.ConclusionsBased on increases in LP-IR scores and BCAA, which each have been shown to predict new onset type 2 diabetes mellitus independent of conventional risk factors in the general population, this preliminary study suggests that diabetes risk is not improved but may even be increased after ADX for APA despite remission of PA.

Initial Glycemic Control and Care Among Younger Adults Diagnosed With Type 2 Diabetes

The prevalence of type 2 diabetes is increasing among adults under age 45. Onset of type 2 diabetes at a younger age increases an individual's risk for diabetes-related complications. Given the lasting benefits conferred by early glycemic control, we compared glycemic control and initial care between adults with younger onset (21-44 years) and mid-age onset (45-64 years) of type 2 diabetes. Using data from a large, integrated health care system, we identified 32,137 adults (aged 21-64 years) with incident diabetes (first HbA1c ≥6.5% [≥48 mmol/mol]). We excluded anyone with evidence of prior type 2 diabetes, gestational diabetes mellitus, or type 1 diabetes. We used generalized linear mixed models, adjusting for demographic and clinical variables, to examine differences in glycemic control and care at 1 year. Of identified individuals, 26.4% had younger-onset and 73.6% had mid-age-onset type 2 diabetes. Adults with younger onset had higher initial mean HbA1c values (8.9% [74 mmol/mol]) than adults with onset in mid-age (8.4% [68 mmol/mol]) (P < 0.0001) and lower odds of achieving an HbA1c <7% (<53 mmol/mol) 1 year after the diagnosis (adjusted odds ratio [aOR] 0.70 [95% CI 0.66-0.74]), even after accounting for HbA1c at diagnosis. Adults with younger onset had lower odds of in-person primary care contact (aOR 0.82 [95% CI 0.76-0.89]) than those with onset during mid-age, but they did not differ in telephone contact (1.05 [0.99-1.10]). Adults with younger onset had higher odds of starting metformin (aOR 1.20 [95% CI 1.12-1.29]) but lower odds of adhering to that medication (0.74 [0.69-0.80]). Adults with onset of type 2 diabetes at a younger age were less likely to achieve glycemic control at 1 year following diagnosis, suggesting the need for tailored care approaches to improve outcomes for this high-risk patient population.

The significance of pigment epithelial detachment in central serous chorioretinopathy.

To investigate the significance of the presence and form of pigment epithelial detachment in the course of central serous chorioretinopathy as well as corticosteroid use as a risk in our patient cohort. Retrospective, single center study of central serous chorioretinopathy patients between January 2013 and January 2019 recording corticosteroid use prior to onset and presence and type of pigment epithelial detachment (flat-irregular, dome-shaped, none) in relationship to disease course. We analyzed 53 eyes of 53 consecutive central serous chorioretinopathy patients treated in our department. Mean patient age was 53 ± 13 years. A flat-irregular pigment epithelial detachment was associated with either chronic or recurrent central serous chorioretinopathy, whereas the absence of a pigment epithelial detachment correlated positively with acute central serous chorioretinopathy (chi-square test, p < 0.05). Of the 53 patients, 10 reported corticosteroid use, 40 denied steroid use, and 3 patients failed to make a clear statement. Corticosteroid use was not correlated with the onset of central serous chorioretinopathy (Student's t-test, p = 0.0001, chi-square test, p < 0.005). A small, flat-irregular pigment epithelial detachment could be a marker for chronic or recurrent central serous chorioretinopathy, whereas the absence of pigment epithelial detachment could favor acute central serous chorioretinopathy. Advanced imaging studies may provide more information on the exact characteristics and nature of pigment epithelial detachments. Corticosteroid use as possible disease trigger was not confirmed in this study.