Biomarkers of Blood Glucose Regulation: 1,5 Anhydroglucitol Glycomark®

Optimal Takeaways

1,5 Anhydroglucitol is a circulating monosaccharide that is usually retained by the kidneys when blood glucose is normal but lost via the kidneys when glucose increases. Low levels in the blood indicate frequent spikes of blood glucose, likely above 160 mg/dL (8.88 mmol/L) (Selvin 2018). Such excursions are considered detrimental and a sign of dysglycemia and future metabolic impairment. Low levels are associated with atherosclerosis and cardiovascular risk as well.

Standard Range: 7.3 - 36.6 ug/mL (44.47 - 222.96 umol/L)

The ODX Range: 24 - 36.6 ug/mL (146.2 - 222.96 umol/L)

Low blood levels of 1,5-AG may be associated with diabetes, as well as microvascular disease, cardiovascular disease, liver disease, kidney disease, carbohydrate restriction, or use of diabetic medications that prevent reabsorption of 1,5-AG (Bergman 2020).

High levels of 1,5-AG don’t appear to have clinical significance.

Overview

1,5-anhydroglucitol (1,5-AG) is a monosaccharide that closely resembles glucose. It is found in many foods as well as in the blood. It is normally reabsorbed by the kidneys when blood glucose remains normal. However, when blood glucose exceeds 160-180 mg/dL (8.88-9.99 mmol/L), it completes with 1,5-AG for reabsorption and more 1,5-AG will be lost in the urine, reducing it in the blood. Blood levels reflect postprandial glucose and low levels can be used as a marker of hyperglycemic postprandial spikes. Levels below 10 ug/mL (61 umol/L) indicate frequent excursions of blood glucose above the renal threshold of 160 mg/dL (8.88 mmol/L) (Selvin 2018).

A 1,5-AG below 11.18 ug/mL (68 umol/L) can be considered a diagnostic cut-off for diabetes with greater sensitivity than hemoglobin A1C (Wang 2017). However, a level of 15.9 ug/mL (96.9 umol/L) or below should trigger further investigation of glucose control as it also may be indicative of diabetes. A very low level of 6 ug/mL (36.6 umol/L) or below significantly increases risk of heart failure, coronary heart disease, stroke, and death (Bergman 2020).

Low 1,5-AG my reflect the presence of atherosclerosis. A retrospective study of acute coronary syndrome patients found that average levels of 1,5-AG were significantly lower in patients who died than those who survived, i.e., 12.3 ug/mL (75 umol/L) versus 19.2 ug/mL (117 umol/L) respectively (Ouchi 2017).

Lower 1,5-AG predicated plaque rupture in diabetics at a significantly lower mean level of 10.5 ug/mL (63.9 umol/L) versus 14.1 ug/mL (85.9 umol/L). Those with plaque rupture also had significantly higher fasting glucose, hs-CRP, and markers of lipid peroxidation (Su 2020).

Manipulation of dietary carbohydrate in the absence of diabetes can also alter 1,5-AG. Reducing glycemic index and limiting carbohydrate intake was found to reduce serum levels of 1,5-AG. Reducing both together had the greatest effect, decreasing 1,5-AG by 3.77 ug/mL (23 umol/L) from a mean of 18.5 ug/mL (112.7 umol/L) despite no documented hyperglycemic excursions (Juraschek 2017). In one study, healthy adults maintained a 1,5-AG of 28.4 ug/mL (173 umol/L) whereas type 2 diabetics maintained a mean of 4.57 ug/mL (27.8 umol/L) (Wang 2012).

References

Bergman, Michael et al. “Review of methods for detecting glycemic disorders.” Diabetes research and clinical practice vol. 165 (2020): 108233. doi:10.1016/j.diabres.2020.108233

Juraschek, S P et al. “Effects of dietary carbohydrate on 1,5-anhydroglucitol in a population without diabetes: results from the OmniCarb trial.” Diabetic medicine : a journal of the British Diabetic Association vol. 34,10 (2017): 1407-1413. doi:10.1111/dme.13391

Ouchi, Shohei et al. “Low 1,5-anhydroglucitol levels are associated with long-term cardiac mortality in acute coronary syndrome patients with hemoglobin A1c levels less than 7.0.” Cardiovascular diabetology vol. 16,1 151. 21 Nov. 2017, doi:10.1186/s12933-017-0636-1

Selvin, Elizabeth et al. “Establishment of Community-Based Reference Intervals for Fructosamine, Glycated Albumin, and 1,5-Anhydroglucitol.” Clinical chemistry vol. 64,5 (2018): 843-850. doi:10.1373/clinchem.2017.285742

Su, Gong et al. “Effect of 1,5-anhydroglucitol levels on culprit plaque rupture in diabetic patients with acute coronary syndrome.” Cardiovascular diabetology vol. 19,1 71. 30 May. 2020, doi:10.1186/s12933-020-01045-0

Wang, Y et al. “A study on the association of serum 1,5-anhydroglucitol levels and the hyperglycaemic excursions as measured by continuous glucose monitoring system among people with type 2 diabetes in China.” Diabetes/metabolism research and reviews vol. 28,4 (2012): 357-62. doi:10.1002/dmrr.2278

Wang, Yao et al. “Serum 1,5-anhydroglucitol level as a screening tool for diabetes mellitus in a community-based population at high risk of diabetes.” Acta diabetologica vol. 54,5 (2017): 425-431. doi:10.1007/s00592-016-0944-z