Fructosamine

Abstract: The glycation of proteins by glucose has been linked to the development of diabetic complications and other diseases. Early glycation is thought to involve the reaction of glucose with N-terminal and lysyl side chain amino groups to form Schiff's base and fructosamine adducts. The formation of the alpha-oxoaldehydes, glyoxal, methylglyoxal and 3-deoxyglucosone, in early glycation was investigated. Glucose (50 mM) degraded slowly at pH 7.4 and 37 degrees C to form glyoxal, methylglyoxal and 3-deoxyglucosone throughout a 3-week incubation period. Addition of t-BOC-lysine and human serum albumin increased the rate of formation of alpha-oxoaldehydes - except glyoxal and methylglyoxal concentrations were low with albumin, as expected from the high reactivity of glyoxal and methylglyoxal with arginine residues. The degradation of fructosyl-lysine also formed glyoxal, methylglyoxal and 3-deoxyglucosone. alpha-Oxoaldehyde formation was dependent on the concentration of phosphate buffer and availability of trace metal ions. This suggests that alpha-oxoaldehydes were formed in early glycation from the degradation of glucose and Schiff's base adduct. Since alpha-oxoaldehydes are important precursors of advanced glycation adducts, these adducts may be formed from early and advanced glycation processes. Short periods of hyperglycaemia, as occur in impaired glucose tolerance, may be sufficient to increase the concentrations of alpha-oxoaldehydes in vivo.

Abstract: OBJECTIVE —The use of diets with low glycemic index (GI) in the management of diabetes is controversial, with contrasting recommendations around the world. We performed a meta-analysis of randomized controlled trials to determine whether low-GI diets, compared with conventional or high-GI diets, improved overall glycemic control in individuals with diabetes, as assessed by reduced HbA 1c or fructosamine levels. RESEARCH DESIGN AND METHODS —Literature searches identified 14 studies, comprising 356 subjects, that met strict inclusion criteria. All were randomized crossover or parallel experimental design of 12 days’ to 12 months’ duration (mean 10 weeks) with modification of at least two meals per day. Only 10 studies documented differences in postprandial glycemia on the two types of diet. RESULTS —Low-GI diets reduced HbA 1c by 0.43% points (CI 0.72–0.13) over and above that produced by high-GI diets. Taking both HbA 1c and fructosamine data together and adjusting for baseline differences, glycated proteins were reduced 7.4% (8.8–6.0) more on the low-GI diet than on the high-GI diet. This result was stable and changed little if the data were unadjusted for baseline levels or excluded studies of short duration. Systematically taking out each study from the meta-analysis did not change the CIs. CONCLUSIONS —Choosing low-GI foods in place of conventional or high-GI foods has a small but clinically useful effect on medium-term glycemic control in patients with diabetes. The incremental benefit is similar to that offered by pharmacological agents that also target postprandial hyperglycemia.

Abstract: This study evaluated the efficacy and safety of rosiglitazone monotherapy in patients with type 2 diabetes. After a 4-week placebo run-in period, 493 patients with type 2 diabetes were randomized to receive rosiglitazone [2 or 4 mg twice daily (bd)] or placebo for 26 weeks. The primary end point was change in hemoglobin A1c; other variables assessed included fasting plasma glucose, fructosamine, endogenous insulin secretion, urinary albumin excretion, serum lipids, and adverse events. Rosiglitazone (2 and 4 mg bd) decreased mean hemoglobin A1c relative to placebo by 1.2 and 1.5 percentage points, respectively, and reduced fasting plasma glucose concentrations relative to placebo by 3.22 and 4.22 mmol/L, respectively. Fasting plasma insulin and insulin precursor molecules decreased significantly. Homeostasis model assessment estimates indicate that rosiglitazone (2 and 4 mg bd) reduced insulin resistance by 16.0% and 24.6%, respectively, and improved β-cell function over baseline by 49.5% and 60.0%, respec...

Abstract: Glucose molecules are joined to protein molecules to form stable ketoamines, or fructosamines, through glycation, a nonenzymatic mechanism involving a labile Schiff base intermediate and the Amadori rearrangement. The amount of fructosamine in serum is increased in diabetes mellitus owing to the abnormally high concentration of sugar in blood. The concentration of fructosamine in serum thus reflects the degree of glycemic control attained by the diabetic patient and is useful in monitoring the effectiveness of therapy in diabetes over a period of several weeks, in a manner analogous to the determination of glycated hemoglobin. Of the analytical approaches used to measure fructosamine, affinity chromatography with m-aminophenylboronic acid and the nitroblue tetrazolium reduction method appear to be the most practical means for clinical chemists to assay fructosamine quickly, economically, and accurately. Fructosamine values can readily distinguish normal individuals and diabetic patients in good glycemic control from diabetics in poor control. Unlike glycated hemoglobin, which reflects the average blood sugar concentration over the past six to eight weeks, fructosamine reflects the average blood sugar concentration over the past two to three weeks. Thus a clinical advantage is that fructosamine responds more quickly to changes in therapy, thereby allowing for improved glycemic control. Used in conjunction with determinations of blood sugar and (or) of glycated hemoglobin, or by itself, the fructosamine assay can provide clinically useful information for the detection and control of diabetes.