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Elevated fructosamine is a sign of dysglycemia over the past 2-4 weeks and should be addressed early on. Circulating fructosamine reflects compounds in the blood that have become glycosylated, meaning those bound by glucose or fructose due to prolonged hyperglycemia. It may be even more sensitive than HbA1C in identifying type 2 diabetes.
Standard Range: 190 - 270 umol/L
The ODX Range: 190 - 228 umol/L
Low fructosamine may be indicative of low serum albumin, rapid albumin turnover, nephrotic syndrome, protein-losing enteropathy, or severe liver disease. In such cases, levels appear falsely decreased (Gounden 2021). Ascorbic acid may also falsely reduce fructosamine results (Pagana 2019).
High fructosamine indicates elevated mean blood glucose levels and poor glycemic control (Gounden 2021). Microvascular complications, retinopathy, and albuminuria are also associated with elevated fructosamine (Selvin 2011, Selvin 2018).
Fructosamine is formed through the glycosylation (glycation) of serum proteins. It represents all glycated proteins in circulation, including globulins and lipoproteins. However, it primarily reflects glycation of albumin, the most abundant circulating protein (Gounden 2021).
Fructosamine levels correlate with fasting glucose and HbA1C and can be useful in assessing glycemic status, even in non-diabetics. Data review from the Atherosclerosis Risk in Communities (ARIC) study revealed that healthy individuals maintained a mean fructosamine of 225.8 umol/L, while higher fructosamine of 261.7 correlated with elevated fasting glucose of 126 mg/dL (6.99 mmol/L), the traditional cut-off for diabetes diagnosis. A fructosamine of 241.4 umol/L correlated with HbA1C of 5.7% (pre-diabetes cut-off), and a level of 261.7 umol/L reflected a HbA1C of 6.5% (diabetes cut-off) (Selvin 2018). An earlier review of the data found that elevated fructosamine was more strongly associated with microvascular complications than HbA1C was (Selvin 2011).
Measuring fructosamine can assist in the early identification of dysglycemia as well as advanced glycation end products. Fructosamine may be superior to HbA1C for monitoring glucose control and variability in the past 2-4 weeks, especially in those with post-prandial glucose spikes or gestational diabetes. Fasting will not alter or interfere with fructosamine measurement and it may be a better screening tool for T2DM than fasting glucose or HbA1c. Malnutrition, thyroid disease, and reduced hepatic protein synthesis can confound results and should be taken into account (Bergman 2020). Fructosamine is especially valuable in assessing glycemic status in sickle cell anemia and other hemoglobinopathies, conditions in which HbA1C measurement is inaccurate (Doumatey 2021).
Nutrition intervention can successfully reduce fructosamine as observed in a prospective trial of 100 individuals with type 2 diabetes. Fructosamine levels decreased significantly from a baseline mean of 311.5 to 297 umol/L in 12 weeks, despite 50-60% of calories coming from carbohydrates (Barakatun 2013). It can be speculated that further improvement of fructosamine and other metabolic parameters such as triglycerides, may be possible with 40-45% of total calories coming from carbohydrates.
Barakatun Nisak, M Y et al. “Medical nutrition therapy administered by a dietitian yields favourable diabetes outcomes in individual with type 2 diabetes mellitus.” The Medical journal of Malaysia vol. 68,1 (2013): 18-23.
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
Doumatey, Ayo P et al. “Serum fructosamine and glycemic status in the presence of the sickle cell mutation.” Diabetes research and clinical practice vol. 177 (2021): 108918. doi:10.1016/j.diabres.2021.108918
Gounden, Verena, et al. “Fructosamine.” StatPearls, StatPearls Publishing, 11 August 2021.
Lee, Ji-Eun. “Alternative biomarkers for assessing glycemic control in diabetes: fructosamine, glycated albumin, and 1,5-anhydroglucitol.” Annals of pediatric endocrinology & metabolism vol. 20,2 (2015): 74-8. doi:10.6065/apem.2015.20.2.74
Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference. Elsevier Health Sciences. 2019.
Selvin, Elizabeth et al. “Nontraditional markers of glycemia: associations with microvascular conditions.” Diabetes care vol. 34,4 (2011): 960-7. doi:10.2337/dc10-1945
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