Value of Serum 1,5-Anhydroglucitol Measurements in Childhood Obesity in the Continuum of Diabetes
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Original article http://dx.doi.org/10.6065/apem.2015.20.4.192 Ann Pediatr Endocrinol Metab 2015;20:192-197 Value of serum 1,5-anhydroglucitol measurements in childhood obesity in the continuum of diabetes Ha Yeong Yoo, MD, Purpose: The prevalence of type 2 diabetes mellitus (T2DM) and obesity are Byung Ok Kwak, MD, currently increasing. Accordingly, the concept of “preventing diabetes” in high- Jae Sung Son, MD, PhD, risk groups has become more important in diabetic care, but the use of glycated Kyo Sun Kim, MD, PhD, hemoglobin (HbA1c) as a measure has limitations in this field. The aim of this Sochung Chung, MD, PhD study was to investigate the utility of 1,5-anhydroglucitol (1,5-AG) in assessing prediabetes status in obese children. Methods: The medical records of 74 subjects aged 6–19 years (of which 27 were Department of Pediatrics, Konkuk overweight/obese and 47 had diabetes) who had 1,5-AG data were reviewed University Medical Center, Konkuk University School of Medicine, Seoul, retrospectively. We compared 1,5-AG with HbA1c using the Pearson correlation test Korea to assess the clinical utility of 1,5-AG. Results: 1,5-AG levels were higher (31.1±10.1 μg/mL vs. 7.4±7.3 μg/mL) and HbA1c levels were lower (5.5%±0.3% vs. 8.9%±2.7%) in the overweight/obese group than in the diabetics group. The range of 1,5-AG levels in obese children was wide (16.8–59.3 μg/mL), and did not have significance with HbA1c. A negative correlation between 1,5-AG and HbA1c was significant in the entire subject r( =–0.822, P<0.001), and also in the HbA1c range of 5.5% to 8% (r=–0.736, P<0.001). Conclusion: 1,5-AG is a valuable index in the HbA1c range of 5.5%–8% and it might be considered an early glycemic control index in insulin-resistant obese children with an HbA1c level above 5.5%. Moreover, the 1,5-AG level assessment should be presented as a supplementary tool for better compliance, as well as being an improvement in diabetes management for the short-term glucose control in relatively well-controlled diabetes patients with an HbA1c level below 8%. Keywords: 1,5-anhydroglucitol, Diabetes mellitus, Obesity, Prediabetic state Introduction The Diabetes Control and Complications Trial emphasized the need to lower glycated hemoglobin (HbA1c) levels to decrease the risk of chronic complication of diabetes1). HbA1c is the gold standard marker of glycemic control and a useful tool in preventing diabetic Received: 8 August, 2015 Revised: 5 September, 2015 complications and educating patients in the clinical setting. Accepted: 19 November, 2015 However, HbA1c has a number of limitations. HbA1c is a mean value of glycemia over 2–3 months and cannot capture daily glucose fluctuations2). It is also unable to distinguish Address for correspondence: between fasting plasma glucose and postprandial blood glucose (PBG)3). Recently, it has been Sochung Chung, MD, PhD suggested that postprandial hyperglycemia and glycemic excursions contribute to the risk of Department of Pediatrics, Konkuk long-term complications in diabetes, increasing their importance in diabetes management4-6). University Medical Center, Konkuk Furthermore, HbA1c levels may be affected in patients with anemia, hemolysis, transfusion, University School of Medicine, 120- renal disease, liver disease, alcoholism, drug use, and genetic hemoglobin abnormalities7,8). 1 Neungdong-ro, Gwangjin-gu, 9) Seoul 05030, Korea Wild et al. estimated the prevalence of diabetes for all age groups to be 4.4% by 2030 and Tel: +82-2-2030-7553 predicted that if the prevalence of obesity increased, the number of diabetics would be much Fax: +82-2-2030-7748 higher than the estimated value. Thus, it is important to detect individuals with prediabetes E-mail: [email protected] This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// ISSN: 2287-1012(Print) creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any ISSN: 2287-1292(Online) medium, provided the original work is properly cited. ©2015 Annals of Pediatric Endocrinology & Metabolism Yoo HY, et al. • 1,5-Anhydroglucitol in childhood obesity and diabetes who are at high-risk for type 2 diabetes mellitus (T2DM) and liquid chromatography using Varaiant TM II turbo (Bio-Rad with undiagnosed diabetes, so that they receive appropriate Laboratories, Hercules, CA, USA). early management10). The three major fundamental components of metabolic 3. The criteria of HbA1c and 1,5-AG disturbances in diabetes are fasting hyperglycemia, postprandial 6) hyperglycemia, and acute glucose fluctuations . According to According to previous study, the level of HbA1c for assessing previous studies, postprandial hyperglycemia and glycemic impaired glucose tolerance (IGT) is 5.5%. And HbA1c>8% is 11-13) excursion are associated with cardiovascular disease . Fre- usually considered to indicate poorly controlled diabetes18). quent checking of self-monitored blood glucose (SMBG) Thus, we divided the subjects into three groups by HbA1c: levels was used to evaluate postprandial hyperglycemia and <5.5%, 5.5%–8%, and >8%. The relationship between 1,5-AG 14) variation in blood glucose levels . However, this has limitations and HbA1c was compared depending on this classification. in reflecting glucose fluctuations precisely. Continuous To determine the reference value of 1,5-AG, we followed glucose monitoring systems (CGMSs) are considered the gold previous studies. Kim and Park19) suggested that diabetes standard for assessing glycemic excursion, but are quite expen- subjects with low 1,5-AG (<10 μg/mL) were more prone to 14,15) sive and invasive for wide application . The compound diabetic complications than those with high 1,5-AG (≥10 μg/ 1,5-anhydroglucitol (1,5-AG) is a glucose analog that declines in mL). In another population-based cohort study in Japan, 23.1 hyperglycemic subjects. Recent studies have shown that 1,5-AG μg/mL was determined as the cutoff value of nondiabetic is reflective of PBG, glucose excursions, and short-term glucose reference subjects20). Thus, we accepted 10 μg/mL as the lower 8,11,14) status . The Food and Drug Administration has recently cutoff, and 23.1 μg/mL as the upper cutoff value of 1,5-AG. validated 1,5-AG as a marker of short-term (2–3 weeks) glucose control status2,16). 4. Statistical analysis The purpose of this study was to assess the clinical utility of 1,5-AG in early diabetes detection in patients with prediabetes Statistical analyses were performed using IBM SPSS Statistics status by comparison with HbA1c in overweight and obese ver. 21.0 (IBM Co., Armonk, NY, USA). Descriptive statistics (OWOB) children. are presented as mean±standard deviation or proportions. Student t-test and one-way analysis of variance (ANOVA) were Materials and methods 1. Study population Table 1. Characteristics and laboratory findings in subjects with OWOB group and diabetes group (n=74) Variable OWOB (n=27) Diabetes (n=47) P-value This study was approved by the Institutional Review Board Age (yr) 12.6±2.9 15.3±3.5 0.002 of Konkuk University Medical Center, Seoul, Korea (IRB No.: Sex, male:female 15:12 15:32 - KUH1090036). The need for informed consent was waived. Body mass index, z-score 1.9±0.7 0.5±1.2 <0.001 In total, 74 participants diagnosed with OWOB (body mass Underweight (z<–1.65) - 1 - index [BMI] z-score ≥1.04, same as the 85th percentile) or Normal (–1.65≤z<1.04) - 30 - diabetes were enrolled between August 2011 and January 2015 Overweight (1.04≤z<1.65) 12 8 - at Konkuk University Medical Center. The subjects (44 girls, Obese (z≥1.65) 15 8 - 30 boys) were 14.3±3.6 years of age and were classified into HbA1c (%) 5.5±0.3 8.9±2.7 <0.001 two groups: OWOB and diabetes. The OWOB group included Glucose (mg/dL) 97.1±10.0 205.8±129.8 <0.001 patients who were overweight (1.04≤BMI z-score<1.65, n=12) 1,5-AG (µg/mL) 31.1±10.1 7.4±7.3 <0.001 or obese (BMI z-score≥1.65, n=15) by 2007 Korean National 17) Ln (1,5-AG) 3.4±0.3 1.5±1.0 <0.001 Growth Charts , and the diabetes group included patients who Creatinine (mg/dL) 0.6±0.1 0.7±0.1 0.001 were type 1 diabetes mellitus (T1DM, n=26) or T2DM (n=21). AST (IU/L) 29.4±12.0 28.3±4.2 0.847 The exclusion criteria included acute or severe chronic diabetes, ALT (IU/L) 37.0±28.7 34.7±53.2 0.839 severe comorbid disorders, and other acute illnesses that Total cholesterol (mmol/L) 173.3±32.9 182.4±46.1 0.366 affected blood glucose. No subject had anemia, chronic kidney LDL cholesterol (mmol/L) 102.7±27.7 98.0±39.4 0.588 disease, or liver failure, and none were pregnant. HDL cholesterol (mmol/L) 48.0±10.1 57.7±15.1 0.004 Triglyceride (mmol/L) 116.2±71.9 118.0±114.6 0.918 2. Biochemical measurement Diabetes duration (yr) - 3.3±3.0 - Values are presented as mean±standard deviation or number. Measurement of serum glycemic markers was performed P-values were calculated by Student t-test. as follows: plasma AG concentrations were measured using OWOB, overweight/obese; HbA1C, glycosylated hemoglobin; Ln an enzymetric colorimetric assay (Kyowa Medex, Tokyo, (1,5-AG), logarithmic transformed 1,5-AG values; AST, aspartate Japan).