Long-term assessment of glucose control by haemoglobin-AGE measurement

doi:10.1016/S0140-6736(96)91141-1

The Lancet

Volume 347, Issue 9000, 24 February 1996, Pages 513-515

https://doi.org/10.1016/S0140-6736(96)91141-1 Get rights and content

Abstract

Summary

Background Control of blood glucose is important in reducing both the incidence and the severity of complications in diabetes mellitus. One consequence of long-term hyperglycaemia is the formation and accumulation of advanced glycation end-products (AGEs) on tissue macromolecules. An AGE-modified form of human haemoglobin (Hb-AGE), present at high levels in the red cells of diabetic patients, differs from the glucose-derived Amadori product HbA1c in being chemically irreversible and thus persisting for the circulating life of the red cell. We therefore compared Hb-AGE with HbA1c as indicators of long-term blood glucose control.

Methods In an open study we measured circulating HbA1c and Hb-AGE concentrations in eight patients with poorly controlled non-insulin-dependent diabetes after a switch to subcutaneous insulin therapy and careful blood glucose monitoring.

Results After 16 weeks of insulin therapy, the mean HbA1c had decreased from 13·3 (SD 1·2) to 7·3 (0·9)% and the mean Hb-AGE from 12·1 (1·5) to 7·3 (1·3) U/mg Hb. The rate of Hb-AGE decline was 23% slower than that of HbA1c (p=0·044).

Interpretation The observation that Hb-AGE declines more slowly than HbA1c is consistent with the irreversible nature of the AGE product. Because of this property, Hb-AGE may prove superior to HbA1c as a long-term index of circulating glucose concentrations.

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Does Lowering Hemoglobin A1c Reduce Penile Prosthesis Infection: A Systematic Review
2021, Sexual Medicine Reviews
Citation Excerpt :
AGEs can alter cell adhesion, change cellular interaction and response, reduce structural stability of tissue, and produce inflammatory cytokines that promote vascular pathology and impair immune function.32 Formation of AGEs is often irreversible, and they are slow to degrade.33 If infection susceptibility is related to AGEs, acutely decreasing HbA1c likely will not affect surgical outcomes.
Hemoglobin A1c (HbA1c), a glycated form of hemoglobin, develops when glucose is elevated in the blood. It is used as a marker of how well a diabetic patient has been controlling their blood sugar over the previous 3–4 months. Some use HbA1c as a predictor of infection risk during prosthetic surgery, and many surgeons require patients to lower it preoperatively.
This study was designed to comprehensively review the literature relating HbA1c and penile prosthesis (PP).
A PubMed search of English-language articles identified studies that investigate the relationship between HbA1c levels and PP infection. Studies were only included if they reported the mean HbA1c of all PP patients and compared patients who did/did not develop a prosthetic infection. References from relevant articles are included.
A total of 6 studies, 1992–2020, were identified. 2 studies occurred before the advent of antibiotic-enhanced devices in the early 2000s and have limited applicability to the modern era. Of the 4 studies published after, 2 reported a significant difference in mean HbA1c when comparing patients who developed a prosthetic infection and those who did not (9.1% vs 7.5%, P = .000 and 9.5% vs 7.8%, P < .001). The other 2 studies reported no significant difference in mean HbA1c when comparing patients who developed a prosthetic infection and those who did not (7.0% vs 7.6%, P > .05; and 7.6% vs 7.5%, P = .598).
Current data regarding HbA1c as a predictor of PP infection are inconclusive, with no consensus. HbA1c is increasingly used as a predictor of postsurgical prosthetic infection, with some urologists requiring patients with elevated HbA1c to acutely lower it before elective surgery. While there are a number of established health benefits of controlling elevated blood sugar, larger randomized controlled trials need to validate whether acutely lowering perioperative HbA1c decreases risk of prosthetic infection.
Dick BP, Yousif A, Raheem O, et al. Does Lowering Hemoglobin A1c Reduce Penile Prosthesis Infection: A Systematic Review. Sex Med Rev 2021;9:628–635.
Centaurium erythraea methanol extract protects red blood cells from oxidative damage in streptozotocin-induced diabetic rats
2017, Journal of Ethnopharmacology
Citation Excerpt :
An improvement of the redox status could result from direct inhibition of free radicals but also from improved glycemic control. In the hyperglycemic condition, the level of non-enzymatically glycated Hb (GlyHb) is elevated and reflects the extent, as well as management of diabetes (Wolffenbuttel et al., 1996). Glycation in diabetics extends beyond hemoglobin to other RBC and serum proteins and leads to the accumulation of advanced glycation end-products (AGEs) that affects the structural and functional properties of proteins and leads to development of diabetic complications (Nawale et al., 2006).
Centaurium erythraea Rafn (CE) is a traditional medicinal herb in Serbia with antidiabetic, digestive, antipyretic and antiflatulent effects
To investigate the potential protective effects of the methanol extract of the aerial parts of CE against glyco-oxidative stress in red blood cells (RBCs) in rats with experimentally induced diabetes.
Diabetes was induced in Wistar rats by intraperitoneal (i.p.) injection of multiple low-dose streptozotocin (STZ) (40 mg/kg, for five consecutive days), with the 1st day after the last STZ injection taken as the day of diabetes onset. The methanol extract of CE (100 mg/kg) was administered orally and daily, two weeks before the first STZ injection, during the 5-day treatment with STZ, and for four weeks after the STZ injections (pre-treated group) or for four weeks after diabetes onset (post-treated group). The effect of CE extract administration on the redox status of RBCs was evaluated by assessing lipid peroxidation, the ratio of reduced/oxidized glutathione (GSH/GSSG), the level of S-glutathionylated proteins (GSSP) and the enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in RBCs four weeks after diabetes onset. The major biochemical parameters of diabetes, protein glycation/glycosylation of erythrocytes and parameters which correlate with their aggregation and deformability were also evaluated.
Daily application of CE extract to STZ-induced diabetic rats provided important antidiabetic effects, observed in both pre-treated and post-treated groups of diabetic rats as elevated serum insulin concentration, reduction of blood glucose and glycated hemoglobin concentrations and an improved lipid profile. Antioxidant effects of CE extract were detected in RBCs of diabetic rats and observed as decreased lipid peroxidation and ameliorated oxidative damage as a result of increased SOD, CAT and GR activities, an improved GSH/GSSG ratio and reduced GSSP levels. Moreover, the CE extract protected RBC proteins from hyperglycemia-induced damage by reducing non-enzymatic glycation and enzymatic glycosylation processes. CE extract was more effective when applied before diabetes induction (pre-treated group).
The results of this study show that the Centaurium erythraea methanol extract protects RBCs in diabetic animals from oxidative damage. They provide additional support for the application of this traditionally used plant in diabetes management.
Effects of S-Allylcysteine on Biomarkers of the Polyol Pathway in Rats with Type 2 Diabetes
2016, Canadian Journal of Diabetes
Citation Excerpt :
This could cause structural, conformational and functional modifications in the erythrocytes. The concentration of glycolated hemoglobin in diabetes proportionately increases with the ambient hyperglycemia and reflects the extent and management of the diabetic condition (34). The elevated level of hemoglobin in the animals treated with SAC may be due to the decreased level of blood glucose.
We evaluated the effects of S-allylcysteine (SAC) on biomarkers of the polyol pathway in streptozotocin-nicotinamide (STZ-NA)-induced diabetes in rats.
Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (55 mg kg⁻¹ bw⁻¹) and NA (110 mg kg⁻¹ bw⁻¹). SAC (150 mg kg⁻¹ bw⁻¹) was orally administered to the rats with diabetes for 45 days to assess its effects on blood glucose, insulin, insulin resistance, glycated hemoglobin, aldose reductase (AR), sorbitol dehydrogenase (SDH), sorbitol, fructose, thiobarbituric acid-reactive substances (TBARS), hydroperoxide, hemoglobin and glutathione (GSH).
On SAC administration in the rats with diabetes, the levels of blood glucose, insulin resistance, glycated hemoglobin, AR, SDH, sorbitol, fructose, TBARS and hydroperoxide increased significantly (p<0.05), whereas those of insulin, hemoglobin and GSH decreased. SAC showed therapeutic effects similar to those of gliclazide in decreasing blood glucose, AR, SDH, sorbitol, fructose, glycosylated hemoglobin, TBARS and hydroperoxides levels and significant increases in insulin, hemoglobin and GSH activity in rats with diabetes. Moreover, histopathologic studies also revealed the protective effect of SAC on pancreatic beta cells.
The results indicate that SAC prevents complications of diabetes by reducing the influx of glucose in the polyol pathway, thereby elevating the GSH level and reducing the activities of AR and SDH. Therefore, SAC may have imperative implications for the deterrence and early treatment of type 2 diabetes.
Nous avons évalué les effets de la S-allyl-cystéine (SAC) sur les biomarqueurs de la voie des polyols du diabète induit par l'administration de streptozotocine et de nicotinamide (STZ-NA) chez les rats.
Nous avons induit le diabète chez des rats Wistar albinos mâles par l'administration par voie intrapéritonéale de STZ (55 mg kg⁻¹ pc⁻¹) et de NA (150 mg kg⁻¹ pc⁻¹). Nous avons administré par voie orale la SAC (150 mg kg⁻¹ pc⁻¹) aux rats diabétiques durant 45 jours pour évaluer ses effets sur la glycémie, l'insuline, l'insulinorésistance, l'hémoglobine glyquée, l'aldose réductase (AR), la sorbitol-déshydrogénase (SDH), le sorbitol, le fructose, les substances réactives à l'acide thiobarbiturique (SRATB), l'hydroperoxyde, l'hémoglobine et le glutathion (GSH).
À l'administration de la SAC chez les rats diabétiques, les concentrations de glycémie, l'insulinorésistance, l'hémoglobine glyquée, l'AR, la SDH, le sorbitol, le fructose, les SRATB et l'hydroperoxyde augmentaient significativement (p < 0,05), alors que celles de l'insuline, de l'hémoglobine et du GSH diminuaient. La SAC montrait des effets thérapeutiques similaires à ceux du gliclazide dans la diminution des concentrations de la glycémie, de l'AR, de la SDH, du sorbitol, du fructose, de l'hémoglobine glyquée, des SRATB et des hydroperoxydes et des augmentations significatives de l'activité de l'insuline, de l'hémoglobine et du GSH chez les rats diabétiques. De plus, les études histopathologiques révélaient également l'effet protecteur de la SAC sur les cellules bêta du pancréas.
Les résultats indiquent que la SAC prévient les complications du diabète en réduisant l'afflux de glucose dans la voie des polyols, augmentant ainsi la concentration du GSH et réduisant les activités de l'AR et de la SDH. Par conséquent, la SAC peut avoir des conséquences impérieuses sur la dissuasion et le traitement précoce du diabète de type 2.
Early formation of serum advanced glycation end-products in children with type 1 diabetes mellitus: Relationship with glycemic control
2016, Journal of Pediatrics
To quantify serum advanced glycation end-products (AGEs) at the onset of type 1 diabetes mellitus and to determine their potential usefulness as retrospective indicators of glycemic balance.
Carboxymethyllysine (CML) and pentosidine concentrations were determined by liquid chromatography–tandem mass spectrometry in 3 groups of children with type 1 diabetes mellitus: group (Gr) 1, subjects included at disease onset (n = 36); Gr2, subjects with diabetes of 5 years duration (n = 48); Gr3, subjects with diabetes of 10 years duration and in control subjects (n = 33). Hemoglobin A1c (HbA1c) values were recorded over the entire course of treatment for assessing long-term glycemic balance.
Serum AGE concentrations were increased in all groups of subjects with diabetes compared with control subjects, but were highest in Gr1 (for CML: 0.155, 0.306, 0.219, and 0.224 mmol/mol Lys in control, Gr1, Gr2, and Gr3 subjects, respectively; for pentosidine: 312, 492, 365, and 403 nmol/mol Lys, respectively). AGE concentrations were closely correlated with HbA1c values (r = 0.78 for CML; r = 0.49 for pentosidine). In Gr2 and Gr3, the overall glycemic balance estimated by average HbA1c values was positively correlated with CML and pentosidine concentrations, especially in the first year of follow-up.
Our results indicate that AGE concentrations are elevated in serum at the time of diabetes mellitus diagnosis, suggesting that the deleterious role of AGEs in the development of long-term complications should be taken into account even at the initial stages of the disease. Moreover, in some circumstances, AGEs could serve as surrogate markers of HbA1c for monitoring glycemic control.
Skin collagen pentosidine and fluorescence in diabetes were predictors of retinopathy progression and creatininemia increase already 6 years after punch-biopsy
2016, Clinical Biochemistry
Advanced glycation end products (AGEs) of collagens appear to contribute to microvascular complications in diabetes. Do high concentrations of AGEs in skin collagen predict accelerated progression of these complications after 6 years and indicate the need for tighter anti-diabetic treatment?
We measured two AGE parameters in collagen extracted from skin punch-biopsies: pentosidine and fluorescence at 370/440 nm, as markers and predictors of microvascular complications, in 30 patients with diabetes (14 type-1, 16 type-2) without renal insufficiency, and in age- and gender-matched normoglycemic controls, followed at Hôtel-Dieu in Paris.
At the time of biopsy, marked increases in pentosidine (p = 0.0014) and fluorescence (p = 0.0001) expressed per collagen hydroxyproline, were found in the patients with diabetes versus the controls. A significant effect of age was found for pentosidine, but not fluorescence, measurements in the normoglycemic controls. Therefore pentosidine but not fluorescence results were corrected for age in the patients. Pentosidine and fluorescence were correlated with diabetes duration. Fluorescence was significantly dependent on retinopathy presence and score in type-1 and type-2 diabetes, whereas pentosidine was not. Fluorescence was correlated with microalbuminuria only in type-1 diabetes. Neither fluorescence nor pentosidine were correlated with creatininemia. Already six years after biopsy, retinopathy score progression and creatininemia increase were significantly correlated with initial pentosidine and fluorescence measurements.
These AGEs are good predictors of progression of microvascular complications and appear to be pathogenic. High skin concentrations of AGEs should induce tighter anti-diabetic treatment.
Relationship between cardiac tissue glycation and skin autofluorescence in patients with coronary artery disease
2015, Diabetes and Metabolism
Citation Excerpt :
AGEs can also be used to assess the prognosis of already diseased humans [8]. The generation of AGEs especially in the extracellular matrix is more pronounced during persistent hyperglycaemia [25], and oxidative and carbonyl stress [12]. AGEs are cleared from the blood by glomerular filtration as modified amino acids after protein degradation.
During ageing, advanced glycation end-products (AGEs) accumulate in extracellular matrix proteins like collagen and contribute to a decline in organ function. As skin autofluorescence (sAF) can assess subcutaneous accumulation of fluorescent AGEs, this study aimed to investigate the relationship between AGE-modified cardiac tissue collagen and AGE-related sAF in coronary artery bypass graft (CABG) surgery patients.
Between January 2011 and January 2012, data from 72 consecutive male patients undergoing isolated CABG were prospectively recorded. Collagen fractions were isolated from the right atrial appendages of these patients by proteolysis and collagenase digestion. Collagen was quantified by hydroxyproline assay, and AGEs by AGE-related intrinsic fluorescence; sAF was measured using an autofluorescence reader.
Biochemical analysis showed that the insoluble cardiac collagen fraction contained the highest amounts of accumulated AGEs; the AGE-related intrinsic fluorescence of this fraction increased with age (P = 0.0001), blood glucose (P = 0.002), HbA_1c (P = 0.01) and sAF (P = 0.008).
This study demonstrated for the first time a relationship between cardiac tissue glycation and AGE-related sAF. In addition, cardiac tissue glycation was associated with age, blood glucose and long-term glucose values in patients with coronary artery disease.

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ArticlesLong-term assessment of glucose control by haemoglobin-AGE measurement

Abstract

Clinica Chimica Acta

J Biol Chem

J Biol Chem

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent mellitus

N Engl J Med

Studies of an unusual hemoglobin in patients with diabetes mellitus

Biochem Biophys Res Commun

Synthesis of hemoglobin A1c in normal and diabetic mice: potential model of basement membrane thickening

Proc Natl Acad Sci USA

Correlation of glucose regulation and hemoglobin A1c in diabetes mellitus

N Engl J Med

The clinical information value of the glycosylated hemoglobin assay

N Engl J Med

Effect of long-term monitoring of glycosylated hemoglobin levels in insulin-dependent diabetes mellitus

N Engl J Med

Temporal relationship of glycosylated haemoglobin concentrations to glucose control in diabetes

Diabetologia

Advanced glycosylation endproducts in tissue and the biochemical basis of diabetic complications

N Engl J Med

The chemistry of the Maillard reaction under physiological conditions: a review

Prog Clin Biol Res

Advanced glycosylation endproducts: role in diabetic and non-diabetic vascular disease

Drug Develop Res

Articles
Long-term assessment of glucose control by haemoglobin-AGE measurement