J Diabetes. 2016 Sep;8(5):712-9.

Effect of renal function on serum concentration of 1,5-anhydroglucitol in type 2 diabetic patients in chronic kidney disease stages I-III: A comparative study with HbA1c and glycated albumin.

Christoph HASSLACHER, Felix KULOZIK

Diabetesinstitut Heidelberg and Department of Clinical Studies at St. Josefskrankenhaus Heidelberg GmbH, Academic Teaching Hospital of the Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.

 

Abstract

BACKGROUND:

1,5-Anhydroglucitol (1,5-AG) is a new blood glucose control marker reflecting temporary glucose elevations. However, 1,5-AG is of limited value in patients with advanced renal insufficiency. The aim of the present study was to assess the correlation between 1,5-AG levels and renal function in patients with earlier stages of nephropathy compared with another two markers of diabetes control, namely HbA1c and glycated albumin (GA).

METHODS:

The following parameters were measured in 377 patients with type 2 diabetes: HbA1c, serum concentrations of 1,5-AG, GA and creatinine, hemoglobin, urinary albumin/creatinine ratio, and urinary excretion of α1 -microglobulin (A1M). Estimated glomerular filtration rate (eGFR) was calculated according to the Cockgroft-Gault formula.

RESULTS:

There was a negative correlation between 1,5-AG and renal function (r = -0.18; P < 0.001). Concentrations of 1,5-AG were, on average, 27.2% lower in patients with glomerular hyperfiltration (eGFR >120 mL/min) compared with patients with moderate renal impairment (eGFR 30-59 mL/min; P = 0.016). In contrast, HbA1c, GA levels and urinary A1M excretion did not differ between the two patient groups. The mean age of patients with eGFR 30-59 mL/min was substantially higher than that of patients with glomerular hyperfiltration (P < 0.001). Thus, an age-related change in the renal glucose threshold could be the reason for the observed correlation between 1,5-AG and renal function.

CONCLUSIONS:

In clinical practice, age and renal function must be taken into consideration when interpreting 1,5-AG levels, even in the absence of advanced renal impairment.

PMID: 26615054; DOI:10.1111/1753-0407.12354

 

Supplementary

Lowering blood glucose levels is well known to be an important factor for preventing or reducing onset of diabetic complications. Aside from the measurement of blood glucose, there are several biomarkers available indicating quality of blood glucose control over different time intervals. HbA1c reflects mean blood glucose levels of the past 2-3 months and is regarded as the gold standard. Glycated albumin (GA), a more recent marker, reflects diabetes control of the past 2-3 weeks (1,2). With the measurement of the serum concentration of 1,5 – anhydroglucitol (1,5-AG) a new marker is available which reflects especially temporary blood glucose elevations during the past 2-3 weeks (3,4).

1,5-AG is a monosaccharide ubiquitously found in food, which is distributed evenly in body fluids and tissues and is not metabolized (5). 1,5-AG is filtrated in renal glomeruli and physiologically almost completely reabsorbed in the proximal tubules in competition with glucose. Consequently in presence of hyperglycemia above the renal threshold 1,5-AG is excreted with the urine and the circulating serum levels of 1,5-AG decrease [6,7]. As temporary excursions of blood glucose are discussed to be of clinical significance for development of vascular complications (8), measurement of 1,5-AG levels seems to be a reasonable supplement for the other two markers, which rarely reflect short term blood glucose peaks.

However, the significance of these biomarkers is limited in patients with advanced stages of nephropathy or dialysis therapy due to several factors. HbA1c values underestimate glucose control due to disturbances of hemoglobin metabolism (9). GA is influenced by higher degrees of proteinuria, resulting in false low values (10). The serum concentration of 1,5-AG is not usable in this patient group, due to disturbances of renal processing of this monosaccharide (11). The impact of glomerular hyperfiltration or moderately impaired renal function on serum concentrations of these biomarkers are unknown. We assessed now the correlation between simultaneously measured levels of HbA1c, GA and 1,5-AG and renal function in 377 type 2 diabetic patients.

The results showed that 1,5-AG levels averaged at 27.2% lower in patients with glomerular hyperfiltration (eGFR > 120 ml/min) compared to patients with moderate renal impairment (eGFR 30 – 59 ml/min; p = 0.016; Fig. 1). Furthermore, we found a strong negative correlation between 1,5 AG-levels and renal function (r = – 0.18; p < 0.001), HbA1c and GA levels were not different between patients with hyperfiltration and moderate renal insufficiency (Fig 1). No significant correlation could be found between GA  levels and renal function.  HbA1c-values showed a positive correlation to eGFR (r = 0.17; p < 0.001), however, regression analysis revealed only a slight increase (0.07% per 10 ml eGFR).

The difference of 1,5-AG levels between patients with glomerular hypofiltration or hyperfiltration is most likely due to a difference in renal processing of 1,5-AG in these stages of kidney disease and not a consequence of different diabetes control, since corresponding changes in HbA1c and GA levels could not be detected. Thus, tubular impairments or changes in the renal threshold for glucose have to be discussed as possible causes for changes in renal processing of 1,5-AG with advancing CKD. Urinary excretion of A1M as a marker of tubular damage did not differ in the various stages of CKD in the present study, excluding an important influence of tubular damage. The patients examined here showed a progression of CKD according to the patients age, and we therefore found a significant positive correlation between 1,5-AG levels and age. As shown in studies on nondiabetic and Type 2 diabetic patients renal glucose threshold increases with age (12,13). Furthermore, an inverse relation between renal function and renal glucose threshold has been described in diabetic patients (14). Therefore we concluded that an increase in the renal threshold due to older age or reduced renal function itself is probably the most important cause for the observed increase in 1,5-AG levels with declining kidney function.

Thus, age and renal function have to be taken into consideration for the interpretation of 1,5-AG levels even in the absence of advanced renal impairment. HbA1c values are only slightly affected by renal function in CKD stages I-III, but GA levels are not.

 

Figure 1: Averaged levels of (a) 1,5-anhydroglucitol, (b) HbA1c and (c) glycated albumin versus renal function (eGFR).

 

Acknowledgement: The study was kindly supported by a grant of Klaus Tschira Stiftung, Heidelberg, Germany.  

 

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Corresponding Author:

Prof. Dr. med. C. Hasslacher,

Diabetesinstitut Heidelberg

c/o St. Josefskrankenhaus, Landhausstr. 25, 69115 Heidelberg, Germany;

Tel.: – 49 6221 6531970

Fax: – 49 6221 6531979

Email: c.hasslacher@diabetesinstitut-hd.de