Glycated albumin levels are higher relative to HbA1c levels in people with autoimmune acute-onset type 1 diabetes mellitus than in people with type 2 diabetes mellitus at the time of diagnosis

Glycated albumin levels are higher relative to HbA1c levels in people with autoimmune acute-onset type 1 diabetes mellitus than in people with type 2 diabetes mellitus at the time of diagnosis

diabetes research and clinical practice 94 (2011) e12–e14 Contents lists available at ScienceDirect Diabetes Research and Clinical Practice jou rnal...

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diabetes research and clinical practice 94 (2011) e12–e14

Contents lists available at ScienceDirect

Diabetes Research and Clinical Practice jou rnal hom ep ag e: w ww.e l s e v i er . c om/ loca te / d i ab r es

Brief report

Glycated albumin levels are higher relative to HbA1c levels in people with autoimmune acute-onset type 1 diabetes mellitus than in people with type 2 diabetes mellitus at the time of diagnosis Masafumi Koga a,*, Jun Murai a, Hiroshi Saito a, Keiko Aoki b, Hideo Kanehara b, Yukihiro Bando b, Shinya Morita c, Soji Kasayma c a

Department of Internal Medicine, Kinki Central Hospital, Hyogo, Japan Department of Internal Medicine, Fukui-ken Saiseikai Hospital, Fukui, Japan c Department of Medicine, Nissay Hospital, Osaka, Japan b

article info

abstract

Article history:

Glycated albumin (GA) is a new glycemic control indicator. GA/HbA1c ratio in autoimmune

Received 19 April 2011

acute-onset type 1 diabetes mellitus patients was significantly higher than in type 2 diabetes

Received in revised form

mellitus patients at the time of diagnosis. This difference might reflect speed of increase in

20 June 2011

plasma glucose after the onset of diabetes.

Accepted 22 June 2011

# 2011 Elsevier Ireland Ltd. All rights reserved.

Published on line 22 July 2011 Keywords: HbA1c Glycated albumin Type 1 diabetes mellitus Type 2 diabetes mellitus

1.

Introduction

HbA1c is used clinically as an indicator for chronic control of plasma glucose levels [1,2]. Since HbA1c reflects plasma glucose levels for the past 2–3 months, it does not reflect glycemic control state at early phase starting treatment for diabetes. Glycated albumin (GA) is a new glycemic control

indicator [3]. Since the half-life of serum albumin is about 14 days, GA reflects shorter-term (about 2 weeks) control of plasma glucose levels [4,5]. We previously reported that in fulminant type 1 diabetes mellitus (FT1DM), a new subtype of type 1 diabetes characterized by acute and almost complete pancreatic b cell destruction without islet-related autoantibodies [6,7], GA/HbA1c ratio in

* Corresponding author at: Department of Internal Medicine, Kinki Central Hospital, Kuruma-zuka 3-1, Itami, Hyogo 664-8533, Japan. Tel.: +81 72 781 3712; fax: +81 72 779 1567. E-mail address: [email protected] (M. Koga). Abbreviations: GA, glycated albumin; AT1DM, autoimmune acute-onset type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; FT1DM, fulminant type 1 diabetes mellitus; BMI, body mass index; ROC, receiver operating characteric. 0168-8227/$ – see front matter # 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2011.06.022

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FT1DM patients was higher than in type 2 diabetes mellitus (T2DM) patients at the time of diagnosis [8]. In autoimmune acute-onset type 1 diabetes mellitus (AT1DM), an autoimmune mechanism causes short-term, specific disruption of pancreatic b cells so that insulin is rapidly depleted, resulting in marked short-term hyperglycemia and ketoacidosis [9]. It may therefore be speculated that the GA/HbA1c ratio will be higher in AT1DM patients than in T2DM patients at the time of diagnosis. Here, this hypothesis was tested by comparing the GA/HbA1c ratios in AT1DM patients and T2DM patients.

2.

Subjects, materials and methods

2.1.

Study patients

Study subjects comprised 17 AT1DM patients [6 men and 11 women, mean age 39.4  20.6 years, body mass index (BMI) 18.8  2.4 kg/m2] who initially visited with ketoacidosis. All patients were positive for anti-GAD antibodies and/or antiislet antigen 2 (IA-2) antibodies. In addition, 29 T2DM patients [21 men and 8 women, mean age 57.9  13.5 years, body mass index (BMI) 23.3  3.7 kg/m2] initially diagnosed with T2DM with symptoms accompanying high plasma glucose levels and no history of diabetes treatment were enrolled as comparison. Exclusion criteria for both groups were: pregnancy, renal, hepatic, hematologic, malignant, thyroid disease, or administration of glucocorticoid. This study was approved by the Ethics Committee at each study hospital. The purpose of the study was explained to all patients, and all patients provided their written informed consent prior to participation in the study.

2.2.

Laboratory methods

HbA1c was measured by high performance liquid chromatography (HPLC). The value for HbA1c (%) is estimated as a National Glycohemoglobin Standardization Program (NGSP) equivalent value (%) calculated by the formula HbA1c (%) = HbA1c (Japan Diabetes Society: JDS) (%) + 0.4%, considering the relational expression of HbA1c (JDS) (%) measured by the previous Japanese standard substance and measurement methods and HbA1c (NGSP) [10]. GA was determined by an enzymatic method using albumin-specific proteinase, ketoamine oxidase, and albumin assay reagent (Lucica GA-L; Asahi Kasei Pharma Co., Tokyo, Japan) [11,12].

2.3.

Statistical analyses

All data are shown as means  SD. For statistical analyses, unpaired Student’s t-test was used to compare two groups. Sensitivities and specificities of GA/HbA1c ratio were calculated and used to generate receiver operating characteristic (ROC) curves [13]. p values of <0.05 were considered significant.

3.

Results

Mean age was significantly younger ( p = 0.014) and mean BMI was significantly lower ( p < 0.001) in the AT1DM

GA/HbA1c Ratio

P<0.0001

5 4 3 2

AT1DM

T2DM

Fig. 1 – Comparison of the glycated albumin (GA)/HbA1c ratio in the patients with the autoimmune acute-onset type 1 diabetes mellitus (AT1DM) (open circles) and the patients with type 2 diabetes mellitus (T2DM) (closed circles). The GA/HbA1c ratio (mean W SD) for each group is also shown. The dotted line represents a GA/HbA1c ratio of 3.4.

patients than in the T2DM patients. There was no significant difference in HbA1c between the AT1DM patients and the T2DM patients (11.7  3.2% vs. 12.5  1.6%, p = 0.230). By contrast, randomly measured plasma glucose was significantly higher in the AT1DM patients than in the T2DM patients (518  197 mg/dL vs. 346  145 mg/dL; p = 0.001). GA was also significantly higher in AT1DM patients than in the T2DM patients (44.7  10.5% vs. 38.8  7.1%; p = 0.027). The GA/HbA1c ratio was significantly higher in the AT1DM patients than in the T2DM patients (3.89  0.47 vs. 3.08  0.36; p < 0.001) (Fig. 1). The GA/HbA1c ratio was >3.4 in 16 of 17 AT1DM patients, while it was the case in 6 of 29 T2DM patients. ROC analyses showed that a cut-off value of 3.4 for the GA/HbA1c ratio yielded 94% sensitivity and 79% specificity for differentiating AT1DM from T2DM (Fig. 2).

4.

Discussion

The GA/HbA1c ratio was significantly higher in the AT1DM patients than in the T2DM patients. In AT1DM patients, endogenous insulin secretion is depleted as a result of destruction of pancreatic b cells mediated by immunological mechanisms, causing precipitous increases in plasma glucose levels accompanied with ketoacidosis [9]. In T2DM patients, plasma glucose levels rise over a long period of time due to reduced insulin release and/or increased insulin resistance [14]. Thus, the rate of increase of plasma glucose is faster in AT1DM patients than in T2DM patients. We previously reported that BMI negatively influences GA [15,16]. When the GA values were corrected for BMI on the basis of the previously reported correlation between BMI and GA in T2DM patients [16], there is a significant difference between the two group ( p < 0.001). This indicates that the higher GA/HbA1c ratio in AT1DM patients is not due to their lower BMI.

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Sensitivity

0.8

0.6

0.4

0.2

0.2

0.4

0.6

0.8

1.0

1-specificity Fig. 2 – Receiver operating characteristic (ROC) curves for the GA/HbA1c ratio for differentiating autoimmune acuteonset type 1 diabetes mellitus (AT1DM) from type 2 diabetes mellitus (T2DM).

Our previous study showed that the GA/HbA1c ratio at diagnosis was significantly higher in FT1DM patients than in T2DM patients [8]. The GA/HbA1c ratio of the AT1DM patients in the present study was comparable to that of the FT1DM patients in the previous study ( p = 0.172). FT1DM develops into ketoacidosis within an extremely short time, and the duration of the disease is shorter than that of AT1DM. It may be speculated that the pre-treatment GA/HbA1c ratio is regulated by both the degree of plasma glucose levels and the disease duration, which is likely the reason why there was no significant difference in the GA/HbA1c ratio between FT1DM patients and AT1DM patients. The sensitivity for differentiating AT1DM from T2DM was 94%, and the specificity 79% in the ROC analysis. Since the GA/ HbA1c ratio can be measured in a short time, it will likely prove to be a useful index for differentiating between AT1DM and T2DM.

Acknowledgements M.K., Y.B. and S.K. researched data, contributed to the discussion, wrote the manuscript, and reviewed/edited the manuscript. J.M., H.S., K.A., H.K., and S.M. researched data.

Conflict of interest The authors declare that they have no conflict of interest.

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