Pediatric T2DM Research Articles

THU150 The Association Between Glycated Albumin And HbA1c In Pediatric Acute Leukemia Patients

Abstract Disclosure: S. Sim: None. M. Ahn: None. B. Suh: None. Introduction: Traditionally, HbA1c has been used as a preferred glycemic index in diabetes patients. However, as many acute leukemia patients often present with anemia and/or pancytopenia, HbA1c may not accurately represent blood glucose level in this group. Glycated albumin represents the average level of blood glucose in recent 2-3 weeks, independent of red blood cell life. In this study, we aim to evaluate the usefulness of glycated albumin as glycemic monitoring index in pediatric patients diagnosed with acute leukemia. Methods: We performed retrospective analysis of a total of 206 pediatric patients from The Seoul St. Mary’s hospital, Catholic university of Korea. Medical records of 25 patients diagnosed with type 2 DM and 66 patients with acute leukemia were investigated for serum glycated albumin, HbA1c, fasting blood glucose level, and demographic data such as sex, age, height, weight and BMI z-scores. 115 children and adolescents who visited our outpatient center for routine child health examination were enrolled as the control group. Results: The median serum glycated albumin levels were 12.4%, 19.1% for acute leukemia and T2DM patients. HbA1c and fasting blood glucose levels, 5.3% and 7.6%, 92mg/dl and 129mg/dl respectively, also differed in the two groups. All glycated albumin, HbA1c and fasting blood glucose level did not appear different in between the control and acute leukemia group. In type 2 DM patients, glycated albumin and HbA1c showed positive correlations (r=0.926, p<0.01). Fasting blood glucose level was also positively correlated to glycated albumin (r=0.821, p<0.001) and HbA1c (r=0.773, p<0.001). While glycated albumin did not appear related to HbA1c in the normal control group (r=-0.02, p=0.824), patients with acute leukemia also revealed a positive correlation between glycated albumin and HbA1c (r=0.253, p=0.04). Glycated albumin was negatively related to BMI z-scores in the control group (r=0.554, p<0.001); however, the level showed no correlation to BMI z-scores in acute leukemia group and in T2DM patients (r=-0.133, p=0.286 and r=-0.292, p=0.156). HbA1c level was positively related to BMI z-scores in the control group (r=0.241, p=0.01) and showed no relations in the other two groups. Regression analysis found glycated albumin to be positively correlated to HbA1c both in acute leukemia pediatric patients and T2DM patients even when adjusted for age, sex and BMI z-score (p=0.039, p=0.007). Conclusion: In acute leukemia patients, glycated albumin may be a complementary parameter of glycemic status as in diabetic patients. Presentation: Thursday, June 15, 2023

ODP185 Diabetic Retinopathy Prevalence in Pediatric Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Abstract Type 2 diabetes mellitus (T2DM) is on the rise in children and adolescents. Diabetic retinopathy (DR) is a leading cause of blindness in adult patients with diabetes. However, the exact prevalence of DR and its determinants in pediatric patients with T2DM are unknown. Understanding the burden of DR in pediatric T2DM can help inform screening and management clinical practice guidelines. This systematic review and meta-analysis aimed to determine the prevalence and determinants of DR in pediatric T2DM. The main outcome was the pooled prevalence of DR in pediatric T2DM. Other important outcomes included the assessment of the impact of diabetes duration, method of retinopathy diagnosis, sex, race, and obesity on prevalence. We searched MEDLINE, Embase, CINAHL, Cochrane Library, Web of Science, and the grey literature from inception until April 4, 2021 for relevant data. No language restrictions were applied, and searches were limited to human studies. Two reviewers independently screened for studies of T2DM patients diagnosed <21 years of age with observational study design and ≥10 participants. Risk of bias evaluation was performed and level of evidence analysis was conducted using the Oxford Centre for Evidence-Based Medicine criteria. A random-effects meta-analysis was used to pool the results. Out of 1849 screened studies, 24 studies met the inclusion criteria. The overall prevalence of DR in pediatric T2DM was 6.58% (95%CI 3.46-10.46, I 2 =96%,n=9026). Most cases were classified as minimal or mild non-proliferative DR. Six cases were sight-threatening. Prevalence was higher in studies using fundoscopy than fundus photography to evaluate DR (0.47% [95%CI 0. 00-3.30, I 2 =0%,n=135] vs. 18.20% [95%CI 7.92-31.28, I 2 =89%,n=718]), suggesting that fundus photography was more sensitive in detecting DR than fundoscopy. The risk of DR rose progressively post-diagnosis; while1.25% (95%CI 0. 00-4. 01, I 2 =13%,n=213) of patients had DR <3 years post T2DM diagnosis, this figure rose to33. 03% (95%CI 25.79-40.66, I 2 =0%,n=162) >5 years after diagnosis. Obesity and sex did not impact DR prevalence. White/Middle Eastern patients had a DR prevalence of 7.43% (95%CI 0. 00-31.37; I 2 =97%,P <0. 001, n=4419),while Asians had a higher prevalence of 14.85% (95%CI 0.91-39.16; I 2 =93%,P <0. 001, n=501). In conclusion, DR is a frequent complication in children and adolescents in the early years post T2DM diagnosis. Screening for DR at diagnosis and annually thereafter using fundus photography is critical to allow early detection and management to prevent visual impairment in these patients. Presentation: No date and time listed

Glycemic control and lipid outcomes in children and adolescents with type 2 diabetes.

BackgroundThe incidence of type 2 diabetes (T2DM) in children has increased dramatically. However, limited published information is known about the glycemic control and lipid outcomes in pediatric T2DM outside of clinical trials.ObjectivesTo determine the glycemic control and lipid measure outcomes at one and three- year follow-up in children with T2DM.MethodsA retrospective electronic medical record review of children with T2DM at the Children’s Hospital of Alabama over a 12-year period.ResultsThere were 301 patients with a diagnosis of T2DM who had a 1-year follow-up visit, of which 184 also had a 3-year follow-up. Most patients (78%) received either insulin with metformin or insulin alone at diagnosis. At one year, 37% of the cohort achieved ‘optimal glycemic control’ (HbA1C ≤6.5%) and 58% of patients achieved durable glycemic control (HbA1C ≤8%). Optimal glycemic control was seen in 48 patients at 3 years. The patients treated with insulin (alone or in combination with metformin) tended to have higher HbA1C at diagnosis, but had improved lipid and glycemic outcomes at follow-up. The group treated with insulin along with metformin had significant improvements in non-HDL, HDL and TC/HDL ratios. The effects of insulin treatment on glycemic control at 3 years were not statistically significant.ConclusionWith the current modality of treatment, only a minority of patients achieve optimal glycemic control at 1 and 3 years of follow-up. Studies are warranted to further elucidate the optimal therapies in the management of pediatric T2DM.

Pharmacokinetics (PK) and Pharmacodynamics (PD) of Canagliflozin (CANA) in Pediatric Patients With Type 2 Diabetes Mellitus (T2DM)

CANA, an SGLT2 inhibitor, increases urinary glucose excretion (UGE) and lowers plasma glucose (PG) levels by reducing the renal threshold for glucose (RTG). In this open-label study, patients aged 10 to <18 y with T2DM on a stable metformin dose (mean age=14.6 y; HbA1c=6.9%; BMI=38 kg/m2) received CANA 100 mg (n=8) or 300 mg (n=9) daily for 14 days. PK parameters were similar to historic parameters measured in adults (Table). At Day 14, CANA dose-dependently reduced mean (SD) RTG to 85 (14) and 69 (10) mg/dL with CANA 100 and 300 mg, respectively. Mean UGE increased from 5 (11) to 74 (37) grams and from 0.1 (0.04) to 69 (27) grams with CANA 100 and 300 mg, respectively. Overall, CANA was well tolerated. In pediatric T2DM patients, CANA had PK parameters similar to adults with T2DM and lowered RTG, increased UGE, and lowered PG concentrations. TablePK Parameters†

Type 2 diabetes in a 5-year-old and single center experience of type 2 diabetes in youth under 10

The worrisome rise in pediatric type 2 diabetes (T2DM) is most prevalent among minority ethnic/racial populations. Typically, T2DM occurs during puberty in high risk obese adolescents with evidence of insulin resistance. Screening for T2DM in obese youth can be a daunting task for pediatricians and differentiating between pediatric T1DM and T2DM in obese youth can be challenging for pediatric endocrinologists. There is very limited data regarding the prevalence of T2DM among youth < 10 years of age. Here we present the case of a 5-year-old Hispanic male diagnosed with T2DM after referral by his pediatrician for abnormal weight gain, acanthosis nigricans and an elevated HbgA1c. He subsequently became symptomatic for diabetes with confirmed hyperglycemia and HbgA1c of 9.7% (83 mmol/mol) at the time of formal diagnosis. Type 1 diabetes autoantibodies (GAD65, Islet, and ZincT8) and monogenic diabetes genetic tests were negative. Due to elevated liver enzymes and baseline HbgA1c, he received basal insulin as his initial therapy. In this paper, we will discuss this case and present an IRB approved retrospective review of the characteristics of the 20 T2DM patients <10 years of age identified to date in our pediatric diabetes center. This review highlights that while uncommon, the diagnosis of T2DM merits consideration even in prepubertal children. This is especially true when working with a high risk population, such as our Hispanic South Texas youth.

Treatment of Pediatric Type 2 Diabetes

To review the current literature for the efficacy and safety of available treatments for type 2 diabetes (T2DM) in the pediatric population. A search from January 1990 to April 2016 was conducted using PubMed and clinicaltrials.gov using the search terms diabetes mellitus, type 2; adolescent; child; and pediatric Bibliographies of chosen articles were reviewed. Relevant articles and preliminary data from clinical trials on metformin, insulin, sulfonylureas, thiazolidinediones (TZDs), glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and α-glucosidase inhibitors for the treatment of pediatric T2DM were reviewed. Studies included randomized controlled, observational, and open-label designs. Metformin, studied in 4 of the reviewed trials, and premixed insulin appear to be safe and effective in pediatric patients with T2DM. TZDs were well tolerated and yielded favorable results, but may have limited applicability. A sulfonylurea had favorable hemoglobin A1C reduction, but was associated with significant weight gain. Studies of incretin-based agents also showed favorable results in the pediatric population but have limited safety and efficacy data. Several trials for other agents are reported on clinicaltrials.gov with unpublished results, but no statistical analyses are reported. Metformin and insulin remain the mainstay of treatment for T2DM in pediatric patients. More robust studies are needed to assist in the provision of evidence-based guidance for the treatment of T2DM in youth.

Use of metformin in pediatric type 2 diabetes

Abstract In the last 10 years the incidence of type 2 diabetes (T2DM) in children and adolescents has increased, due to increasing prevalence of obesity in youth. Therefore, the prevalence of diabetes-related complications such as hypertension, hyperlipidemia and microalbuminuria has also increased in pediatric T2DM. The pathogenesis of T2DM in children involves genetic and environmental factors that will determine the increase of insulin resistance and decrease of beta pancreatic insulin secretion. Only metformin and insulin are approved for clinical use in children in the majority of countries. The aim of this paper is to review the benefits of the treatment with metformin in children and adolescents with T2DM.

Dyslipidemia in children with type 2 diabetes vs. obesity

To compare the frequency and severity of dyslipidemia between subjects with type 2 diabetes (T2DM) and non-diabetic obese group (OB) subjects, followed in a pediatric subspecialty clinic. One hundred and four OB subjects seen consecutively by one physician and 67 pediatric subjects diagnosed with T2DM (negative antibodies) were screened from an institutional review board-approved database. Fifty-two T2DM and 75 OB subjects with fasting lipid profiles measured at one hospital's laboratory were included. Both OB and T2DM subjects were predominantly Mexican American. Comparing T2DM at diagnosis or uncontrolled (UC) and OB, mean +/- SD age was 14.3 +/- 2.3 and 11.4 +/- 3.7 with body mass index-Z score of 2.02 +/- 0.67 and 2.46 +/- 0.45, respectively (both p < 0.01). Comparing lipid levels in T2DM to OB and National Health and Nutrition Examination Survey III, the percentage of subjects, respectively, with cholesterol >200 mg/dL (5.17 mmol/L) were 55.8, 22.7, and 10%; with low-density lipoprotein >130 mg/dL (3.36 mmol/L) were 39.4, 12.5, and 10%; with triglycerides >150 mg/dL (1.68 mmol/L) were 65.1, 38.7, and 12.5%; and with high-density lipoprotein <35 mg/dL (0.91 mmol/L) were 40, 22.2, and 10%. Over 80% of the T2DM subjects improved their lipid profile with improved glycemic control as hemoglobin A1c decreased from 10.85 +/- 2.17 to 7.6 +/- 2%. Dyslipidemia is a frequent comorbidity of obesity and T2DM, starting in childhood, and poses a major public health risk. Dyslipidemia in pediatric subjects with UC T2DM is significantly worse than in OB subjects but is similar to OB subjects when diabetes was better controlled. Earlier use of lipid-lowering drugs should be considered in pediatric T2DM patients who achieve tight glycemic control, yet their dyslipidemia persists.