The 2007 international consensus about the standardization of HbA(1c) determination and expression of results is progressively implemented in most countries. In France, a common working group of the Société française de biologie clinique (SFBC) and the Société francophone de diabétologie (SFD) has expressed the following recommendations. HbA(1c) results are expressed in percentage of total hemoglobin and in mmol HbA(1c)/mol Hb, but are not converted into estimated average glucose. A table indicating the correspondence between HbA(1c) and estimated average glucose may be given with the results, subject to precautions of interpretation at the individual level.

L’hémoglobine glyquée (HbA1c) représente le paramètre clé de la surveillance de l’équilibre glycémique des patients diabétiques. Son dosage est assuré par des techniques bien contrôlées, dont il importe de connaître les avantages et les limites lors de l’interprétation des résultats en pratique clinique. L’HbA1c peut être prise en défaut en cas d’anomalie du métabolisme de l’hémoglobine ou du globule rouge, ou en présence de certains variants d’hémoglobine, et peut être remplacée par le dosage des fructosamines. Les dosages de l’HbA1c sont standardisés par rapport à une méthode de référence internationale, permettant l’obtention de résultats comparables d’une méthode et d’un laboratoire à un autre. Cette standardisation, basée sur une méthodologie plus spécifique, est de nature à modifier l’expression des résultats d’HbA1c (mmol/mol, au lieu de pourcentages), selon un calendrier et un programme à déterminer dans chaque pays. Le dosage de l’HbA1c peut être appelé à s’étendre au dépistage et au diagnostic du diabète sucré, comme cela a été recommandé dans différents pays. L’HbA1c reste donc un outil d’avenir dans la prise en charge des patients diabétiques.Hemoglobin A1c (HbA1c) is the key parameter of diabetic patient glycemic control survey. Its assay is performed by well-controlled techniques, whose advantages and limitations must be known upon result interpretation in clinical practice. HbA1c may be caught out in case of troubles of hemoglobin or red blood cell metabolism, or in the presence of some hemoglobin variants, and may be replaced by fructosamine assay. HbA1c assays are standardized against an international reference method, which allows to obtain comparable results from one method and one laboratory to another. This standardization, based on a more specific methodology, leads to modify HbA1c value expression (mmol/mol instead of percentages), according to a schedule and an implementation program to be determined in every country. HbA1c assay is likely to be extended to screening and diagnosis of diabetes mellitus, as already recommended in different countries. Thus, HbA1c remains a full of future promise tool in diabetic patient care.

The 2007 international consensus about the standardization of HbA(1c) determination and expression of results is progressively implemented in most countries. In France, a common working group of the Societe francaise de biologie clinique (SFBC) and the Societe francophone de diabetologie (SFD) has expressed the following recommendations. HbA1c results are expressed in percentage of total hemoglobin and in mmol HbA1c/mol Hb, but are not converted into estimated average glucose. A table indicating the correspondence between HbA1c and estimated average glucose may be given with the results, subject to precautions of interpretation at the individual level.

Auteur(s) : P Gillery1,6, M Bordas-Fonfrede2,6, JP Chapelle3,6, G Hue4,6, C Perier5,6 1Laboratoire de biologie et de recherche pediatriques, American Memorial Hospital, Centre hospitalier universitaire de Reims 2Laboratoire de biochimie metabolique, Pole de biologie medicale, Groupe hospitalier Pitie-Salpetriere, Paris 3Departement de biologie clinique, Centre hospitalier universitaire de Liege, Belgique 4Laboratoire de biochimie medicale, Hopital Charles Nicolle, Centre hospitalier [...]

Two patients presented massive hypercholesterolemia related to acquired disease, intrahepatic cholangitis with cholestasis in one and nephrotic syndrome in the second. Comparison of the lipoprotein patterns demonstrated distinctive pathophysiological processes different from those operating in primary causes of hypercholesterolemia.

La denutrition proteique accroit la fragilite et aggrave la morbidite intercurrente generalement observee au grand âge. Cette denutrition est due a une insuffisance d' apport alimentaire et a un etat hypercatabolique. Les apports nutritionnels quotidiens en glucides, lipides, proteines et calcium ont ete mesures chez des personnes âgees hospitalisees ( n= 49) tirees au sort, en pesant les aliments fournis avant les repas et les aliments residuels apres les repas. Parallelement l'etat stable ou hypercatabolique et les facteurs de risque de denutrition etaient consideres pour chaque patient inclus dans l'etude. La comparaison des apports nutritionnels a ete etablie en fonction de l'etat metabolique stable ou de l'etat hypercatabolique. Chez les patients en etat metabolique stable les apports nutritionnels spontanees en proteines, lipides, glucides sont ceux des recommandations a l'exception des apports en calcium ( apport calorique total : 1535 ± 370 Cal/ j ; proteines : 1 ± 0.4 g / j ; glucides 55 ± 7.7 % ; lipides 30 ± 6.3 % ; calcium : 918 ± 341 mg/j). Les patients en etat hypercatabolique ( insuffisance cardiorespiratoire instable, neuropathologie degenerative, reaction inflammatoire) ont des apports caloriques totaux et un apport nutritionnel proteique abaisses et associes a un deficit majeur en apport calcique ( apport calorique total : 1375 ± 500 Cal/j ; proteines : 0.9 ± 0.4 g/kg/j ; glucides : 54 ± 8.3 % ; lipides : 31± 6.2 % ; calcium : 866 ± 379 mg/j). Les apports nutritionnels abaisses chez les patients hospitalises dans les unites de court sejour etaient probablement la consequence d' un defaut d' appreciation des exigences nutritionnelles satisfaisantes. La denutrition proteique doit etre diagnostiquee tres tot lors de l' hospitalisation afin d' envisager une supplementation nutritionnelle appropriee. Toutefois l'incidence de la denutrition proteique au grand âge comme cause ou comme consequence de processus physiopathologiques fait l'objet de discussion.

A massive release of troponin Ic and CKMB was described in a patient during septic shock. According to experimental animal models previously described, this release of biological markers by myocardial tissue could be due to an inflammatory process of myocardial tissue during septic shock without myocardial infarction in non cardiac critically ill patients.

L’observation presentee est celle d’un patient caucasien, diabetique, âge de 47 ans. La determination de l’HbA1c par HPLC (Variant II Biorad laboratories-hemoglobin A1c program) a mis en evidence la presence d’HbF (1 %) et une augmentation d’HbA1c (10 %). La presence d’HbF a conduit a realiser une electrophorese en gel d’agarose (Sebia) revelant la presence du variant Hb Athens-Georgia chez ce patient. Ainsi, la presence d’HbF, seul stigmate d’eventuelle anomalie hematologique, devrait conduire a la realisation d’une electrophorese de l’hemoglobine exploratrice de l’existence d’un variant Hb rare, silencieux du point de vue clinique ou d’une augmentation non suspectee d’HbA2.

The following report concerned a 47 year old Caucasian diabetic patient. Routine HPLC of HbA1c (Variant II Biorad Laboratories - hemoglobin A1c program) resulted only in the evidence of HbF (1%) and increase in HbA1c (10%). Considering the presence of HbF a standard agarose gel electrophoresis of patient's hemoglobin was performed and revealed the presence of Hb Athens-Georgia. Consequently the occurrence of HbF during determination of HbA1c by HPLC should lead to perform a standard hemoglobin electrophoresis in order to explore an hidden, unsuspected and clinically silent occurrence of rare Hb variant or additional unsuspected increase in HbA2.

Protein undernutrition enhances frailty and aggravates intercurrent diseases generally observed in elderly patients. Undernutrition results from insufficient food intake and catabolic status. Daily nutrient intakes were explored for hospitalized geriatric patients. Nutrient intake (carbohydrates, lipids, proteins, and calcium) was determined in randomly selected geriatric patients (n=49) over five consecutive days by weighting food in the plate before and after meals. For each geriatric patient, catabolic status and risk factors of undernutrition were considered. Results were compared between patients in a steady status or catabolic status. In steady status patients, protein, lipid and carbohydrate intake but not calcium intake, met recommended dietary allowances (total caloric intake:1535 +/- 370 Cal/day ; protein:1+/- 0.4 g/kg/day ; carbohydrates:55 +/- 7.7 % ; lipids: 30 +/- 6.3 % ; calcium:918 +/- 341 mg/day) . Patients in catabolic status (cardiopulmonary deficiency , neurologic disease , inflammatory process) had lower total caloric intake, lower protein intake and dramatically lower calcium intake (total caloric intake : 1375 +/- 500 Cal/day ; protein :0.9 +/- 0.4 g/kg/day ; carbohydrates : 54 +/- 8.3 % ; lipids : 31 +/-6.2 % ; calcium : 866 +/- 379 mg/day). Nutrient intake was lower in elderly patients hospitalized in short stay care units, perhaps due to failure to recognize suitable nutrient requirements. Protein-caloric undernutrition should be diagnosed early during hospitalization in order to allow appropriate dietary supplementation. However the incidence of protein undernutrition among elderly patients as a cause or a consequence of adverse pathophysiological processes remains a cause of debate.

Structural and functional alterations of proteins are observed during aging. Glycation of long half-life proteins, involving reducing carbohydrates, leads to the formation of intra and intermolecular cross-links and the production of free radicals. These processes depend on the amount of glucose available and on molecular oxygen which contributes to the production of free radicals. These processes are observed without dysfunction of carbohydrate metabolism and progress with age. However, whether this process is a primary cause or a consequence of aging remains a question of debate. Prevention of excessive glycoxidation could be a goal of recommendations designed to control the tissular alterations occurring in aging.

The course of glycation of calf skin fibrous type I collagen was monitored in vitro under physiological conditions during an 8-week incubation period in order to take into account the long half-life of this protein. The formation of glycated compounds was measured by determining fructosamine, pentosidine, and carboxymethyllysine content. The incubation conditions were as physiological as possible in sterile saline phosphate buffer, except glucose concentration. With incubation medium containing 200 mmol glucose, fibrous collagen underwent solubilization; in addition an increase in fructosamine, pentosidine, and carboxymethyllysine content in both solubilized and remaining insoluble collagen was noticed. There was a spontaneous, restricted, and time-dependent native glycated state of collagen; high concentration glucose enhanced the formation of glycated compounds and induced changes in solubility and glycoxidated products. The production of pentosidine during incubation without glucose should be considered as an event resulting from the initial fructosamine. Whereas the production of carboxymethyllysine during long-term incubation with glucose provided indirect proof of an additional oxidative process after early glycated product formation. These experimental observations provide insight into the in vivo context of advanced glycation end product formation in chronic hyperglycemia and aging.

The deleterious effects of glycoxidation are dependent on the half-life of proteins. Collagen, the main component of extracellular matrices, is a long live protein and thus may be sensitive to the glycoxidation process. We incubated calf skin fibrous type I collagen in PBS at 37°C with glucose. The fibrous type I collagen was solubilized and an increase in the amount of advanced glycation end products of the solubilized fraction was observed. As there was no bacterial contamination and no proteolytic activities in the incubation medium, the solubilization of fibrous type I collagen is probably due to the speculative production of the free radicals in our experimental conditions. To test this hypothesis, fibrous type I collagen was incubated in PBS with AAPH (2,2′azo-bis 2-aminodinopropane) a free radicals generator. AAPH induced a dramatic and dose dependent solubilization of fibrous type I collagen.

BACKGROUND:Loss of collagen and elastin is observed in the elderly. In geriatric inpatients, chronic protein malnutrition could induce susceptibility to additional morbidity such as pressure sores.OBJECTIVE:The purpose of this study was to explore the relationship between nutritional and inflammatory status and the production of tissue inhibitor of matrix metalloproteinase 1 (TIMP-1).METHODS:Chronically ill elderly inpatients, without or with pressure sores, were enrolled. Nutritional protein markers, acute phase reactants, and TIMP-1 were determined, and changes in these biological parameters were compared.RESULTS:Chronic inflammatory process and protein malnutrition were observed in all enrolled patients. The severity of these two pathophysiological processes was independent of the occurrence of pressure sores. The serum prealbumin and albumin levels were lower in patients with pressure sores than in those without. In addition, the general increase in the TIMP-1 level was independent of the occurrence of pressure sores. The TIMP-1 level was mainly related to the prognostic inflammatory and nutritional index.CONCLUSIONS:The general increase in acute-phase reactants observed in the elderly could be related to the intercurrent diseases. The generally low serum albumin level, lowest in patients with pressure sores, may be considered evidence of protein malnutrition and hypercatabolism. Regarding the morbidity, the increase in TIMP-1 levels could be explained as an adaptive process to prevent intrinsic protein expenditure of extracellular matrices.

Pentosidine, an advanced glycation end product (AGE), was assayed by HPLC in serum proteins from patients with Alzheimer type dementia (AD), patients with diabetes mellitus (D), and healthy (C) age-matched old subjects (mean age from each group = 84 years). Serum pentosidine was significantly different between the three groups despite similar renal function (serum creatinine < 160 micromol/L). In all groups of patients, pentosidine was independent of glycated hemoglobin (HbA1C) and the early glycation marker fructosamine and appeared to be an independent marker, mainly bound to serum albumin. Pentosidine could be an important factor useful for the diagnosis of Alzheimer's disease.

This paper describes a qualitative immunoreactivity cholecystokinin (CCK) characterization in 24 hours urine specimens. Urine was subjected to ethanol precipitation, followed by ion exchange chromatography, and immunoblotting with 2 antibodies. HPLC was developed to authenticate qualitatively the presence of CCK revealed by immunoblotting.The results obtained by HPLC showed this method was more specific. HPLC allowed us to distinguish, through anti-CCK reactive fractions, a single peak which reacted only with CCK antibodies and not with gastrin antibodies.