The prevalence of type 2 diabetes mellitus (T2DM) and obesity are currently increasing. Accordingly, the concept of "preventing diabetes" in high-risk groups has become more important in diabetic care, but the use of glycated hemoglobin (HbA1c) as a measure has limitations in this field. The aim of this study was to investigate the utility of 1,5-anhydroglucitol (1,5-AG) in assessing prediabetes status in obese children.
The medical records of 74 subjects aged 6-19 years (of which 27 were overweight/obese and 47 had diabetes) who had 1,5-AG data were reviewed retrospectively. We compared 1,5-AG with HbA1c using the Pearson correlation test to assess the clinical utility of 1,5-AG.
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 (
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%.
The Diabetes Control and Complications Trial emphasized the need to lower glycated hemoglobin (HbA1c) levels to decrease the risk of chronic complication of diabetes
However, HbA1c has a number of limitations. HbA1c is a mean value of glycemia over 2-3 months and cannot capture daily glucose fluctuations
Wild et al.
The three major fundamental components of metabolic disturbances in diabetes are fasting hyperglycemia, postprandial hyperglycemia, and acute glucose fluctuations
The purpose of this study was to assess the clinical utility of 1,5-AG in early diabetes detection in patients with prediabetes status by comparison with HbA1c in overweight and obese (OWOB) children.
This study was approved by the Institutional Review Board of Konkuk University Medical Center, Seoul, Korea (IRB No.: KUH1090036). The need for informed consent was waived. In total, 74 participants diagnosed with OWOB (body mass index [BMI]
Measurement of serum glycemic markers was performed as follows: plasma AG concentrations were measured using an enzymetric colorimetric assay (Kyowa Medex, Tokyo, Japan). And, HbA1c was assayed by high-performance liquid chromatography using Varaiant TM II turbo (Bio-Rad Laboratories, Hercules, CA, USA).
According to previous study, the level of HbA1c for assessing impaired glucose tolerance (IGT) is 5.5%. And HbA1c>8% is usually considered to indicate poorly controlled diabetes
To determine the reference value of 1,5-AG, we followed previous studies. Kim and Park
Statistical analyses were performed using IBM SPSS Statistics ver. 21.0 (IBM Co., Armonk, NY, USA). Descriptive statistics are presented as mean±standard deviation or proportions. Student t-test and one-way analysis of variance (ANOVA) were used to compare the mean values of variables. Logarithmic transformation of the 1,5-AG values was performed to assess the linear correlation between logarithmic transformed 1,5-AG values (ln [1,5-AG]) and HbA1c. We compared 1,5-AG with HbA1c using the Pearson correlation test.
The clinical characteristics of the subjects are presented in
In OWOB group, the mean age was 12.6±2.9 years, the HbA1c was 5.5%±0.3%, and the 1,5-AG was 31.1±10.1 µg/mL. In Diabetes group, the mean age was 15.3±3.5 years, the levels of HbA1c was 8.9%±2.7%, and the 1,5-AG was significantly lower than OWOB group as 7.4±7.3 µg/mL. The mean duration of diabetes was 3.3±3.0 years.
The mean age of the OWOB group was 12.6±2.9 years, younger than that of the diabetes (15.3±3.5 years). The levels of HbA1c and glucose were significantly lower, whereas 1,5-AG was higher in the OWOB group than in the diabetes group (31.1±10.1 µg/mL vs. 7.4±7.3 µg/mL,
The subjects were divided into 3 subgroups according to HbA1c: <5.5%, 5.5%-8%, and >8%. The patient's characteristics and the average values of the clinical parameters (age, gender, BMI
Most of the subjects with HbA1c<5.5% were in the OWOB group, except one who had well-controlled T2DM. This group showed substantial variation in 1,5-AG (17.9-44.3 µg/mL), and had no correlation between 1,5-AG and HbA1c levels. For HbA1c>8%, all subjects were diabetics and none of the OWOB were included. The 1,5-AG levels were 2.4±1.1, in the range of 0.6-4.9 µg/mL, and also 1,5-AG did not correlate with HbA1c. However, for the HbA1c range of 5.5%-8%, each 1,5-AG was distributed more widely in the range of 3.8-59.3 µg/mL, and correlated significantly with HbA1c (
1,5-AG is a six-carbon monosaccharide, the 1-deoxy form of glucose, that was first discovered in 1888
The amount of 1,5-AG is generally maintained at approximately 500-1,000 mg in total
1,5-AG is suitable for evaluating short-term glucose status, glucose excursions, and PBG and thus is suitable for use in monitoring strict glycemic control
Recently, markedly increased T2DM, even in children, could lead to profound economic costs for diabetic care and managing complications related to diabetes, and the importance of identifying prediabetics has increased
In this study, we compared 1,5-AG with HbA1c, the "traditional" standard marker of glycemic control, in the OWOB and diabetes groups. The 1,5-AG levels were significantly inversely correlated with HbA1c 5.5%-8%. The 1,5-AG values of diabetes subjects overlapped with the OWOB group when HbA1c was ≤8%, whereas most of the poorly controlled diabetics (HbA1c>8%) had prominently low levels of 1,5-AG, and showed no correlation between 1,5-AG and HbA1c, and this result was consistent with a previous report on severely uncontrolled diabetes
As mentioned earlier, 1,5-AG might be a more valuable marker of a detailed glucose status for the segment with HbA1c≤8%. This may imply that 1,5-AG better reflects glycemic changes of prediabetes than HbA1c. It was previously reported that serum 1,5-AG concentrations were lower in nondiabetic subjects with a family history of T2DM than in those with no family history
1,5-AG is a valuable index in the HbA1c range 5.5%-8% and it might be considered as an early glycemic control index in obese patients with HbA1c levels of more than 5.5%., such as IGT or insulin-resistant obese children. Also, 1,5-AG level assessments should be stressed as a supplementary tool for better compliance as well as improvement of short-term glucose control in diabetes management in relatively well-controlled diabetes patients with an HbA1c level of less than 8%.
This study had several limitations. First, it is a retrospective study based on past medical records. Second, the small sample size and short follow-up durations of diabetes were additional limitations. Third, we could not examine patient glucose variability or peak glucose levels by CGMS or SMBG and were unable to include patients with large glucose variability. However, we did not select specific patients, thus more accurately reflecting a realistic diabetic population. Further studies are needed for 1,5-AG to be recognized as an early glycemic marker in prediabetes.
Variable | OWOB (n=27) | Diabetes (n=47) | P-value |
---|---|---|---|
Age (yr) | 12.6±2.9 | 15.3±3.5 | 0.002 |
Sex, male:female | 15:12 | 15:32 | - |
Body mass index, z-score | 1.9±0.7 | 0.5±1.2 | <0.001 |
Underweight (z<-1.65) | - | 1 | - |
Normal (-1.65≤z<1.04) | - | 30 | - |
Overweight (1.04≤z<1.65) | 12 | 8 | - |
Obese (z≥1.65) | 15 | 8 | - |
HbA1c (%) | 5.5±0.3 | 8.9±2.7 | <0.001 |
Glucose (mg/dL) | 97.1±10.0 | 205.8±129.8 | <0.001 |
1,5-AG (µg/mL) | 31.1±10.1 | 7.4±7.3 | <0.001 |
Ln (1,5-AG) | 3.4±0.3 | 1.5±1.0 | <0.001 |
Creatinine (mg/dL) | 0.6±0.1 | 0.7±0.1 | 0.001 |
AST (IU/L) | 29.4±12.0 | 28.3±4.2 | 0.847 |
ALT (IU/L) | 37.0±28.7 | 34.7±53.2 | 0.839 |
Total cholesterol (mmol/L) | 173.3±32.9 | 182.4±46.1 | 0.366 |
LDL cholesterol (mmol/L) | 102.7±27.7 | 98.0±39.4 | 0.588 |
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 |
Diabetes duration (yr) | - | 3.3±3.0 | - |
Values are presented as mean±standard deviation or number.
OWOB, overweight/obese; HbA1C, glycosylated hemoglobin; Ln (1,5-AG), logarithmic transformed 1,5-AG values; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDL, low-density lipoprotein; HDL, high-density lipoprotein.
Variable | HbA1C<5.5% (n=12) | 5.5%≤HbA1C≤8% (n=38) | HbA1C>8% (n=24) | |
---|---|---|---|---|
Age (yr) | 11.9±3.4 | 14.3±3.6a) | 15.5±3.0a) | 0.017* |
Sex, male:female | 7:5 | 15:23 | 8:16 | 0.358 |
Body mass index, z-score | 1.8±0.3 | 1.2±1.3a) | 0.3±2.5a) | 0.002* |
HbA1c (%) | 5.3±0.2 | 6.4±0.8 | 11.0±2.2 | <0.001* |
Glucose (mg/dL) | 96.0±10.9a) | 124.4±52.6a) | 267.3±148.2 | <0.001* |
1,5-AG (µg/mL) | 29.6±9.0 | 20.4±13.2 | 2.4±1.1 | <0.001* |
Ln (1,5-AG) | 3.3±0.3 | 2.8±0.7 | 0.7±0.6 | <0.001* |
Creatinine (mg/dL) | 0.5±0.1 | 0.7±0.1a) | 0.7±0.1a) | 0.007* |
AST (U/L) | 28.8±10.5 | 24.5±10.7 | 35.3±38.8 | 0.223 |
ALT (U/L) | 34.4±28.3 | 28.2±23.2 | 47.8±71.5 | 0.262 |
Total cholesterol (mmol/L) | 170.8±44.8a) | 168.8±26.2a) | 199.5±53.1 | 0.012* |
LDL cholesterol (mmol/L) | 100.0±37.4 | 93.2±27.5 | 110.0±43.8 | 0.194 |
HDL cholesterol (mmol/L) | 47.8±10.1 | 53.0±12.3 | 59.1±17.3 | 0.061 |
Triglyceride (mmol/L) | 113.2±42.1 | 99.6±72.8 | 148.9±145.7 | 0.169 |
Values are presented as means±standard deviation or number.
HbA1C, glycosylated hemoglobin; Ln (1,5-AG), logarithmic transformed 1,5-AG values; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDL, low-density lipoprotein; HDL, high-density lipoprotein.
a),b)Statistical significance was assessed by one-way analysis of variance among groups. The same letters indicate a nonsignificant difference between groups based on the Scheffe multiple comparison test. *
Group | ||
---|---|---|
Total | -0.822 | <0.001 |
Diabetes (T1DM:T2DM, 26:21) | -0.719 | <0.001 |
OWOB (overweight:obese, 12:15) | -0.007 | 0.972 |
HbA1c | ||
≤8% (OWOB:diabetes, 27:23) | -0.746 | <0.001 |
5.5% (OWOB:diabetes, 11:1) | 0.041 | 0.900 |
5.5%-8% (OWOB:diabetes, 16:22) | -0.736 | <0.001 |
>8% (OWOB:diabetes, 0:24) | -0.126 | 0.557 |
Ln (1,5-AG), logarithmic transformed 1,5-AG values; HbA1C, glycosylated hemoglobin; r, Pearson correlation coefficient; T1DM, type1 diabetes mellitus; T2DM, type2 diabetes mellitus; OWOB, overweight/obese.