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Haemoglobin
Kinds of Haemoglobin Terms modified by Haemoglobin Selected AbstractsHaemoglobin and anaemia in a gender perspective: The Tromsř Study,EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2005Tove Skjelbakken Abstract:,Objectives:,To examine the gender-specific distribution of haemoglobin (Hb) and the World Health Organization (WHO) criteria for anaemia compared with the 2.5 percentile for Hb. Methods:,A population-based study from Tromsř, Northern Norway. All inhabitants above 24 yr were invited. In total, 26 530 (75%) had their Hb analysed. Results:,The 2.5,97.5 percentile of Hb was 129,166 and 114,152 g/L for all men and women, respectively. In men, mean Hb decreased from 148 to 137 g/L between 55,64 and 85+ yr. In women, mean Hb increased from 132 to 137 g/L between 35,44 and 65,74 yr and then decreased to 131 g/L among the oldest. Using the WHO criteria for anaemia (Hb: <130 and <120 g/L, men and women respectively), the prevalence of anaemia in men increased with age from 0.6% aged 25,34 to 29.6% aged 85+. For women, the prevalence of anaemia varied from 9.1%, 2.2% and 16.5% in the age groups of 35,44, 55,64 and 85+ yr, respectively. The WHO criteria gave a two to three times higher prevalence of anaemia compared with the 2.5 percentile of Hb in women, but the difference was small in men. Poor self-rated health was not associated with low values of Hb in women. In men, there was an association in some age groups. Conclusion:,The WHO criteria for anaemia and the 2.5 percentile for Hb corresponded well for men, but not for women. The WHO criteria of anaemia may result in medicalization of healthy women. [source] Effects on acid-base balance, methaemoglobinemia and nitrogen excretion of European eel after exposure to elevated ambient nitriteJOURNAL OF FISH BIOLOGY, Issue 3 2002C.-Y. Huang Haemoglobin, methaemoglobin, blood nitrite concentration and acid-base balance were measured in European eel Anguilla anguilla following exposure to 0 (control), 0·142, 0·356, 0·751 and l·549 mM nitrite in fresh water for 24 h. Blood GOT (glutamate oxaloacetate transaminase) and GPT (glutamate pyruvate transaminase) activities and whole animal ammonia-N and urea-N excretions were also measured. Blood nitrite, methaemoglobin, PO2 (oxygen partial pressure), GOT, and whole animal ammonia-N excretion and urea-N excretion increased directly with increasing ambient nitrite concentrations, whereas blood pH, PCO2, and HCO,3 were inversely related to ambient nitrite concentration. An accumulation of nitrite in the blood of A. anguilla following 24 h exposure to elevated ambient nitrite as low as 0·751 mM increased its blood methaemoglobin, PO2, GOT and nitrogen excretion, but decreased its PCO2 (carbon dioxide partial pressure), HCO,3 and functional haemoglobin. [source] Pentoxifylline improves haemoglobin and interleukin-6 levels in chronic kidney diseaseNEPHROLOGY, Issue 3 2010PAOLO FERRARI ABSTRACT Aim: To assess whether pentoxifylline improves anaemia of chronic kidney disease (CKD) via suppression of interleukin-6 (IL-6) and improved iron mobilization. Background: CKD patients may have elevated IL-6 and tumour necrosis factor alpha levels. These cytokines can increase hepcidin production, which in turn reduces iron release from macrophages resulting in reduced availability of iron for erythropoiesis. In experimental models, pentoxifylline was shown to reduce IL-6 expression. Methods: We studied 14 patients with stages 4,5 CKD (glomerular filtration rate <30mL/min per 1.73 m2) due to non-inflammatory renal diseases. None of the patients had received immunosuppressive or erythropoietin-stimulating agents or parenteral iron. Patients had weekly blood tests for iron studies and cytokines during a control run-in period of 3 weeks and during 4 weeks of pentoxifylline treatment. Results: Ten patients (eGFR 23 ± 6 mL/min) completed the study. At the end of the run-in period average haemoglobin was 111 ± 5 g/L, ferritin 92 ± 26 µg/L, transferrin saturation 15 ± 3% and circulating IL-6 10.6 ± 3.8 pg/mL. Tumour necrosis factor alpha values were below threshold for detection. Treatment with pentoxifylline reduced circulating IL-6 (6.6 ± 1.6 pg/mL, P < 0.01), increased transferrin saturation (20 ± 5%, P < 0.003) and decreased serum ferritin (81 ± 25 µg/L, P = NS). Haemoglobin increased after the second week of pentoxifylline, reaching 123 ± 6 g/L by week 4 (P < 0.001). Conclusions: Pentoxifylline reduces circulating IL-6 and improves haemoglobin in non-inflammatory moderate to severe CKD. These changes are associated with changes in circulating transferrin saturation and ferritin, suggesting improved iron release. It is hypothesized that pentoxifylline improves iron disposition possibly through modulation of hepcidin. [source] Prevalence of anaemia and the contribution of functional iron deficiency in diabetes related chronic kidney diseasePRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 3 2010MRCP Specialist Registrar in Diabetes & Endocrinology, MS Rathi MBBS Abstract Anaemia is often an unrecognised complication of diabetes that has an adverse effect on the progression of diabetes related complications. Anaemia predicts mortality in diabetes related chronic kidney disease (CKD). Contributors to its development include absolute and/or functional iron deficiency and erythropoietin insufficiency. This study aimed to look at the prevalence of anaemia and markers of iron deficiency in patients with diabetes related CKD. An analysis was done of the results from all patients (225 men, 93 women; mean age 70 years) attending joint diabetes,renal clinics over a 12-month period. Haemoglobin (Hb) was measured in 88%. The mean Hb was 12.6g/dl in men and 11.7g/dl in women. A total of 21.5% (11.5% men, 10% women) had Hb <11g/dl who should have anaemia management as per National Institute for Health and Clinical Excellence guidelines. Among the anaemic population, CKD stage 3 was present in 25% of men and in 8% of women, with CKD stage 4 present in 20% of men and in 32% of women. Fifty-three percent had absolute iron deficiency (serum ferritin <100,g/L) and 41% had inadequate iron stores (serum ferritin between 100 and 500,g/L). Functional iron deficiency defined by serum ferritin >100,g/L and red cell hypochromasia ,6% was noted in 21.6% of anaemic patients. Anaemia is a frequent finding in patients with diabetes related CKD. A significant proportion of patients had functional iron deficiency that required iron therapy for optimisation of their iron stores before starting erythropoiesis-stimulating agents. Measurement of red cell hypochromasia is a valuable tool to detect this group of patients. Copyright © 2010 John Wiley & Sons. [source] Avian haemoglobins and structural basis of high affinity for oxygen: structure of bar-headed goose aquomet haemoglobinACTA CRYSTALLOGRAPHICA SECTION D, Issue 6 2001Xiao-Zhou Liu Haemoglobin from the bar-headed goose (Anser indicus) has higher oxygen affinity than that from its lowland relatives such as greylag goose (A. anser). The crystal structure of bar-headed goose aquomet haemoglobin was determined at 2.3,Ĺ resolution and compared with the structures of the goose oxy, human, horse and other avian haemoglobins and the sequences of other avian haemoglobins. Four amino-acid residues differ between greylag goose and bar-headed goose haemoglobins, among which Ala,119 and Asp,125 in bar-headed goose haemoglobin reduces the contacts between the ,1 and ,1 subunits compared with Pro and Glu, respectively, and therefore may increase the oxygen affinity by loosening the ,1,1 interface. Compared with human oxy haemoglobin, the relative orientation of two ,, dimers in the bar-headed goose aquomet and oxy Hbs are rotated by about 4°, indicating a unique quaternary structural difference from the typical R state. This new `RH' state is probably correlated with the higher oxygen affinity of bar-headed goose haemoglobin. [source] Purification, crystallization and preliminary crystallographic study of haemoglobin from camel (Camelus dromedarius): a high oxygen-affinity lowland speciesACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 8 2009M. Balasubramanian Haemoglobin is a prototypical allosteric protein that is mainly involved in the transportation of oxygen from the lungs to tissues and of carbon dioxide back to the lungs in an intrinsically coordinated manner to maintain the viability of cells. Haemoglobin from Camelus dromedarius provides an interesting case study of adaptation to life in deserts at extremely high temperatures. An ambition to unravel the integrated structural and functional aspects of the casual survival of this animal at high temperatures led us to specifically work on this problem. The present work reports the preliminary crystallographic study of camel haemoglobin. Camel blood was collected and the haemoglobin was purified by anion-exchange chromatography and crystallized using the hanging-drop vapour-diffusion method under buffered high salt concentration using PEG 3350 as a precipitant. Intensity data were collected using a MAR 345 dtb image-plate detector system. Camel haemoglobin crystallized in the monoclinic space group P21, with one whole biological molecule (,2,2) in the asymmetric unit and unit-cell parameters a = 52.759, b = 116.782, c = 52.807,Ĺ, , = 120.07°. [source] Purification, crystallization and preliminary X-ray analysis of haemoglobin from ostrich (Struthio camelus)ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 7 2009S. S. Sundaresan Haemoglobin is a tetrameric protein that carries oxygen from the lungs to tissues and carbon dioxide from tissues back to the lungs. The oxygen-binding properties of haemoglobin are regulated through the binding of allosteric effectors. The respiratory system of avian species is unique and complex in nature when compared with that of mammals. In avian species, inositol pentaphosphate (inositol-P5) is present in the erythrocytes of the adult and is thought to be the major factor responsible for the relatively high oxygen affinity of the whole blood. The ostrich (Struthio camelus) is a large flightless bird which contains inositol tetrakisphosphate (inositol-P4) in its erythrocytes and its whole blood oxygen affinity is higher. Efforts have been made to explore the structure,function relationship of ostrich haemoglobin. Ostrich haemoglobin was purified using ion-exchange chromatography. Haemoglobin crystals were grown by the hanging-drop vapour-diffusion method using PEG 3350 as the precipitant in 50,mM phosphate buffer pH 7.2. Data were collected using a MAR345 image-plate detector system. The crystals of ostrich haemoglobin diffracted to 2.2,Ĺ resolution. They belonged to the orthorhombic space group P212121 with one whole biological molecule in the asymmetric unit; the unit-cell parameters were a = 80.93, b = 81.68, c = 102.05,Ĺ. [source] Purification, crystallization and preliminary crystallographic study of low oxygen-affinity haemoglobin from cat (Felis silvestris catus) in two different crystal formsACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 3 2009M. Balasubramanian Haemoglobin is a metalloprotein which plays a major role in the transportation of oxygen from the lungs to tissues and of carbon dioxide back to the lungs. The present work reports the preliminary crystallographic study of low oxygen-affinity haemoglobin from cat in different crystal forms. Cat blood was collected, purified by anion-exchange chromatography and crystallized in two different conditions by the hanging-drop vapour-diffusion method under unbuffered low-salt and buffered high-salt concentrations using PEG 3350 as a precipitant. Intensity data were collected using MAR345 and MAR345dtb image-plate detector systems. Cat haemoglobin crystallizes in monoclinic and orthorhombic crystal forms with one and two whole biological molecules (,2,2), respectively, in the asymmetric unit. [source] Purification, crystallization and preliminary X-ray diffraction studies on avian haemoglobin from pigeon (Columba livia)ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 2 2009Pon. Sathya Moorthy Haemoglobin is a physiologically significant metalloprotein that is involved in the exchange of gases for sustaining life. The respiratory system of birds is unique and complex compared with that of mammals. Many investigations of avian haemoglobins have revealed the presence of inositol pentaphosphate (IP5), a principal allosteric effector that is involved in regulation of their function. Structural investigations of avian haemoglobins are presently not adequate to explain their function. Efforts have been made in this direction in order to understand the oxygen-binding affinity involved in adapting to hypoxia in avian haemoglobins. Fresh whole blood was collected from pigeon (Columba livia) and purified using a DEAE cellulose anion-exchange chromatographic column. Crystallization of pigeon haemoglobin was accomplished using the hanging-drop vapour-diffusion method using PEG 3350 as a precipitant in 50,mM sodium acetate buffer pH 5.5 with 1,M NaCl. Data collection was carried out using a MAR345 image-plate detector system. The crystals diffracted to 2,Ĺ resolution. Pigeon haemoglobin crystallizes in a triclinic space group, with two whole biological molecules in the asymmetric unit and with unit-cell parameters a = 55.005, b = 65.528, c = 104.370,Ĺ, , = 78.742, , = 89.819, , = 65.320°. [source] Effects of vitamin A deficiency during pregnancy on maternal and child healthBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 6 2002M.S. Radhika Objective To examine the association between biochemical vitamin A deficiency in pregnancy and maternal and fetal health. Design A cross sectional clinical study. Setting Antenatal clinic of nutrition unit of Niloufer Hospital catering for a low socio-economic population, and a private nursing home (Swapna nursing home) catering for a high socio-economic population. Population 736 pregnant women in their third trimester of pregnancy belonging to low (n= 522) and high socio-economic groups (n= 214). Methods All the women were subjected to a detailed clinical, anthropometric and obstetric examination. Night blindness was assessed by administering the standard WHO questionnaire. Birthweight and gestational age of the infants, maternal anaemia and development of pregnancy-induced hypertension in the mother were recorded. Haemoglobin and serum retinol were estimated at the time of recruitment to the study. Main outcome measures Serum retinol levels, anaemia, pregnancy-induced hypertension, birthweight and gestational age of the infant. Results Night blindness was observed in 2.9% of the women and subclincal vitamin A deficiency (serum retinol <20 ,g/dL with no clinical signs) in 27% of the women. Moderate to severe anaemia was observed in 41.2% of the women, and 15.8% of the women developed pregnancy-induced hypertension. Sixty-one (9.4%) women delivered preterm. Univariate analysis identified a significant association between serum retinol <20 ,g/dL and preterm delivery (OR = 1.74, 95% CI 1.03,2.96), maternal anaemia (OR = 1.82, 95% CI 1.28,2.60) and pregnancy-induced hypertension (OR = 1.56, 95% CI 1.02,2.83). After adjusting for the confounding variables (body mass index, parity, age and socio-economic status) in a multivariate analysis, the significant associations between serum retinol <20 ,g/dL and preterm delivery (P= 0.02) and anaemia (P= 0.003) persisted, while that for pregnancy-induced hypertension disappeared (P= 0.71). Conclusion The study suggests that subclinical vitamin A deficiency is a problem during the third trimester of pregnancy. Serum concentration of retinol <20 ,g/dL appears to indicate a deficient status, and is associated with an increased risk of preterm delivery and maternal anaemia. [source] Crystallization, preliminary X-ray analysis and molecular-replacement solution of haemoglobin-II from the fish matrinxă (Brycon cephalus)ACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2003J. C. L. Fonseca Haemoglobins constitute a set of proteins with interesting structural and functional properties, especially when the two large animal groups reptiles and fishes are focused on. Here, the crystallization and preliminary X-ray analysis of haemoglobin-II from the South American fish matrinxă (Brycon cephalus) is reported. X-ray diffraction data have been collected to 3.0,Ĺ resolution using synchrotron radiation (LNLS). Crystals were determined to belong to space group P21 and preliminary structural analysis revealed the presence of two tetramers in the asymmetric unit. The structure was determined using the standard molecular-replacement technique. [source] Oxygen-dependent ion transport in erythrocytesACTA PHYSIOLOGICA, Issue 3 2009A. Bogdanova Abstract The present contribution reviews current knowledge of apparently oxygen-dependent ion transport in erythrocytes and presents modern hypotheses on their regulatory mechanisms and physiological roles. In addition to molecular oxygen as such, reactive oxygen species, nitric oxide, carbon monoxide, regional variations of cellular ATP and hydrogen sulphide may play a role in the regulation of transport, provided that they are affected by oxygen tension. It appears that the transporter molecules themselves do not have direct oxygen sensors. Thus, the oxygen level must be sensed elsewhere, and the effect transduced to the transporter. The possible pathways involved in the regulation of transport, including haemoglobin as a sensor, and phosphorylation/dephosphorylation reactions both in the transporter and its upstream effectors, are discussed. [source] Exenatide: a review from pharmacology to clinical practiceDIABETES OBESITY & METABOLISM, Issue 6 2009R. Gentilella Background:, Exenatide is an incretin mimetic that activates glucagon-like-peptide-1 receptors. It blunts the postprandial rise of plasma glucose by increasing glucose-dependent insulin secretion, suppressing inappropriately high glucagon secretion and delaying gastric emptying. Methods:, In seven clinical trials performed in 2845 adult patients with type 2 diabetes mellitus who were inadequately controlled by a sulphonylurea and/or metformin (glycosylated haemoglobin, HbA1c ,11%), or by thiazolidinediones (with or without metformin) and treated for periods from 16 weeks to 3 years, exenatide (5 ,g b.i.d. s.c. for the first 4 weeks of treatment and 10 ,g b.i.d. s.c. thereafter) reduced HbA1c, fasting and postprandial glucose, and body weight dose dependently, and was similar to insulin glargine and biphasic insulin aspart in reducing HbA1c. Body weight diminished with exenatide, whereas it increased with both insulin preparations. Positive effects on the lipid profile and a reduction in C-reactive protein were also recorded with exenatide. Treatment extensions up to 3 years showed that benefits were maintained in the long term. Adverse events were usually mild to moderate in intensity, and generally the frequency decreased with continued therapy. The most common was nausea (whose incidence may be reduced by gradual dose escalation from 5 ,g b.i.d. to 10 ,g b.i.d.), vomiting, diarrhoea, headache and hypoglycaemia (almost exclusively in patients treated with a sulphonylurea). Results and conclusions:, Exenatide is a new, promising therapeutic option for type 2 diabetic patients inadequately controlled by oral agents, before insulin therapy, offering the added benefits of body weight reduction and tight postprandial glucose control. [source] Insulin therapy in type 2 diabetes: what is the evidence?DIABETES OBESITY & METABOLISM, Issue 5 2009Mariëlle J. P. Van Avendonk Aim:, To systematically review the literature regarding insulin use in patients with type 2 diabetes mellitus Methods:, A Medline and Embase search was performed to identify randomized controlled trials (RCT) published in English between 1 January 2000 and 1 April 2008, involving insulin therapy in adults with type 2 diabetes mellitus. The RCTs must comprise at least glycaemic control (glycosylated haemoglobin (HbA1c), postprandial plasma glucose and /or fasting blood glucose (FBG)) and hypoglycaemic events as outcome measurements. Results:, The Pubmed search resulted in 943 hits; the Embase search gave 692 hits. A total of 116 RCTs were selected by title or abstract. Eventually 78 trials met the inclusion criteria. The studies were very diverse and of different quality. They comprised all possible insulin regimens with and without combination with oral medication. Continuing metformin and/or sulphonylurea after start of therapy with basal long-acting insulin results in better glycaemic control with less insulin requirements, less weight gain and less hypoglycaemic events. Long-acting insulin analogues in combination with oral medication are associated with similar glycaemic control but fewer hypoglycaemic episodes compared with NPH insulin. Most of the trials demonstrated better glycaemic control with premix insulin therapy than with a long-acting insulin once daily, but premix insulin causes more hypoglycaemic episodes. Analogue premix provides similar HbA1c, but lower postprandial glucose levels compared with human premix, without increase in hypoglycaemic events or weight gain. Drawing conclusions from the limited number of studies concerning basal,bolus regimen seems not possible. Some studies showed that rapid-acting insulin analogues frequently result in a better HbA1c or postprandial glucose without increase of hypoglycaemia than regular human insulin. Conclusion:, A once-daily basal insulin regimen added to oral medication is an ideal starting point. All next steps, from one to two or even more injections per day should be taken very carefully and in thorough deliberation with the patient, who has to comply with such a regimen for many years. [source] Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitusDIABETES OBESITY & METABOLISM, Issue 5 2009E. Bosi Aim:, To compare the efficacy and safety of vildagliptin and metformin initial combination therapy with individual monotherapies in treatment-naive patients with type 2 diabetes mellitus (T2DM). Methods:, This was a 24-week, randomized, double-blind, active-controlled study. Treatment-naive patients with T2DM who had a glycated haemoglobin (HbA1c) of 7.5,11% (N = 1179) were randomized equally to receive vildagliptin plus high-dose metformin combination therapy (50 mg + 1000 mg twice daily), vildagliptin plus low-dose metformin combination therapy (50 mg + 500 mg twice daily), vildagliptin monotherapy (50 mg twice daily) or high-dose metformin monotherapy (1000 mg twice daily). The primary objective was to demonstrate that HbA1c reduction from baseline with either combination therapy is superior to both monotherapies at the week 24 endpoint. Patients who failed glycaemic-screening criteria [HbA1c >11% or fasting plasma glucose (FPG) >15 mmol/l (270 mg/dl)] could enter a 24-week, single-arm substudy. These patients (N = 94) received open-label vildagliptin plus high-dose metformin combination therapy (100 mg + 1000 mg twice daily). Results:, From comparable baseline values (8.6,8.7%), HbA1c decreased in all four treatment groups, to the greatest extent with vildagliptin plus high-dose metformin combination therapy. Mean (SE) HbA1c change from baseline was ,1.8% (0.06%), ,1.6% (0.06%), ,1.1% (0.06%) and ,1.4% (0.06%) with vildagliptin plus high-dose metformin combination therapy, vildagliptin plus low-dose metformin combination therapy, and vildagliptin and metformin monotherapies respectively. The between-group difference was superior with vildagliptin plus high-dose metformin combination therapy (p < 0.001 vs. both monotherapies) and vildagliptin plus low-dose metformin combination therapy (p < 0.001 and p = 0.004, vs. vildagliptin and metformin monotherapies, respectively). Higher baseline HbA1c values were linked to greater HbA1c reductions, with changes of ,3.2% (0.22%), ,2.7% (0.22%), ,1.5% (0.24%) and ,2.6% (0.26%) respectively, occurring in patients with baseline HbA1c,10%. Reductions in FPG were superior with vildagliptin plus high-dose metformin combination therapy [change from baseline ,2.63 (0.13) mmol/l] compared with both monotherapies [,1.26 (0.13) mmol/l and ,1.92 (0.13) mmol/l, respectively; p < 0.001]. There was no incidence of hypoglycaemia or severe hypoglycaemia with either combination therapy, and neither was associated with weight gain. All treatments were well tolerated and displayed a comparable incidence of adverse events overall. Despite superior HbA1c lowering, the vildagliptin plus low-dose metformin combination therapy group demonstrated a favourable gastrointestinal (GI) tolerability profile compared with metformin monotherapy. Conclusions:, In treatment-naive patients, combinations of vildagliptin and both high-dose and low-dose metformin provide superior efficacy to monotherapy treatments with a comparable overall tolerability profile and low risk of hypoglycaemia. The potential dose-sparing effect of adding vildagliptin to low-dose metformin in preference to the up-titration of metformin may allow patients to achieve equivalent or superior HbA1c lowering without the GI tolerability issues associated with higher doses of metformin. [source] Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapyDIABETES OBESITY & METABOLISM, Issue 2 2009E. Ferrannini Aim:, To examine the efficacy and safety of vildagliptin vs. glimepiride as add-on therapy to metformin in patients with type 2 diabetes mellitus in a 52-week interim analysis of a large, randomized, double-blind, multicentre study. The primary objective was to demonstrate non-inferiority of vildagliptin vs. glimepiride in glycosylated haemoglobin (HbA1c) reduction at week 52. Methods:, Patients inadequately controlled on metformin monotherapy (HbA1c 6.5,8.5%) and receiving a stable dose of metformin (mean dose 1898 mg/day; mean duration of use 36 months) were randomized 1:1 to receive vildagliptin (50 mg twice daily, n = 1396) or glimepiride (titrated up to 6 mg/day; mean dose 4.5 mg/day, n = 1393). Results:, Non-inferiority of vildagliptin was demonstrated (97.5% confidence interval 0.02%, 0.16%) with a mean (SE) change from baseline HbA1c (7.3% in both groups) to week 52 endpoint of ,0.44% (0.02%) with vildagliptin and ,0.53% (0.02%) with glimepiride. Although a similar proportion of patients reached a target HbA1c level of <7% with vildagliptin and glimepiride (54.1 and 55.5%, respectively), a greater proportion of patients reached this target without hypoglycaemia in the vildagliptin group (50.9 vs. 44.3%; p < 0.01). Fasting plasma glucose (FPG) reductions were comparable between groups (mean [SE] ,1.01 [0.06] mmol/l and ,1.14 [0.06] mmol/l respectively). Vildagliptin significantly reduced body weight relative to glimepiride (mean [SE] change from baseline ,0.23 [0.11] kg; between-group difference ,1.79 kg; p < 0.001) and resulted in a 10-fold lower incidence of hypoglycaemia than glimepiride (1.7 vs. 16.2% of patients presenting at least one hypoglycaemic event; 39 vs. 554 hypoglycaemic events, p < 0.01). No severe hypoglycaemia occurred with vildagliptin compared with 10 episodes with glimepiride (p < 0.01), and no patient in the vildagliptin group discontinued because of hypoglycaemia compared with 11 patients in the glimepiride group. The incidence of adverse events (AEs), serious AEs and adjudicated cardiovascular events was 74.5, 7.1 and 0.9%, respectively, in patients receiving vildagliptin, and 81.1, 9.5 and 1.6%, respectively, in patients receiving glimepiride. Conclusions:, When metformin alone fails to maintain sufficient glycaemic control, the addition of vildagliptin provides comparable efficacy to that of glimepiride after 52 weeks and displays a favourable AE profile, with no weight gain and a significant reduction in hypoglycaemia compared with glimepiride. [source] Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapyDIABETES OBESITY & METABOLISM, Issue 2 2009R. E. Pratley Aim:, To evaluate the efficacy and safety of alogliptin, a potent and highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, in combination with glyburide in patients with type 2 diabetes inadequately controlled by sulphonylurea monotherapy. Methods:, After a 2-week screening period, adult patients 18,80 years of age entered a 4-week run-in/stabilization period in which they were switched from their own sulphonylurea medication to an equivalent dose of glyburide (open label) plus placebo (single blind). After the run-in period, patients were randomly assigned to double-blind treatment with alogliptin 12.5 mg (n = 203), alogliptin 25 mg (n = 198), or placebo (n = 99) for 26 weeks. The primary end-point was change from baseline to week 26 in glycosylated haemoglobin (HbA1c). Secondary end-points included clinical response rates and changes in fasting plasma glucose, ,-cell function (fasting proinsulin, insulin, proinsulin/insulin ratio, and C-peptide, and homeostasis model assessment ,-cell function), body weight, and safety end-points [adverse events (AEs), clinical laboratory tests, vital signs and electrocardiographic readings]. Results:, The study population had a mean age of 57 years and a mean disease duration of 8 years; it was well balanced for gender (52% women) and was mainly white (71%). The mean baseline HbA1c was approximately 8.1% in each group. Significantly greater least squares (LS) mean reductions in HbA1c were seen at week 26 with alogliptin 12.5 mg (,0.38%) and 25 mg (,0.52%) vs. placebo (+0.01%; p < 0.001), and more patients in the alogliptin 25-mg group had HbA1c levels ,7.0% at week 26 (34.8%, p = 0.002) vs. placebo (18.2%). Proportionately more patients in the alogliptin 12.5 mg (47.3%) and 25 mg (50.5%) groups had an HbA1c reduction ,0.5% from baseline compared with patients in the placebo group (26.3%; p < 0.001). Minor improvements in individual markers of ,-cell function were seen with alogliptin, but no significant treatment group differences were noted relative to placebo. Minor LS mean changes in body weight were noted across groups (placebo, ,0.20 kg; alogliptin 12.5 mg, +0.60 kg; alogliptin 25 mg, +0.68 kg). AEs were reported for 63,64% of patients receiving alogliptin and 54% of patients receiving placebo. Few AEs were treatment limiting (2.0,2.5% across groups), and serious AEs (2.0,5.6%) were infrequent, similar across groups, and generally considered not related to treatment. The incidences of hypoglycaemia for placebo, alogliptin 12.5 mg and alogliptin 25 mg groups were 11.1, 15.8 and 9.6% respectively. Conclusions:, In patients with type 2 diabetes inadequately controlled by glyburide monotherapy, the addition of alogliptin resulted in clinically significant reductions in HbA1c without increased incidence of hypoglycaemia. [source] Insulin analogues: an example of applied medical scienceDIABETES OBESITY & METABOLISM, Issue 1 2009B. Sheldon Insulin analogues were developed to try and achieve more physiological insulin replacement from injection in the subcutaneous site. Their pharmacokinetics and pharmacodynamics differ from human insulin when injected subcutaneously because of alterations in the amino acid sequence of the insulin molecule. The rapid-acting insulin analogues, lispro, aspart and glulisine, have a rapid onset of action and shorter duration of action because of changes to the B26,30 portion of insulin inhibiting formation of dimers and hexamers. They appear to improve postprandial glucose, incidence of hypoglycaemia and patient satisfaction and, when used in combination with basal insulin analogues, improve glycosylated haemoglobin in comparison to conventional insulin therapy. Additionally, they have been successfully used in children, pregnant women, in pump therapy and as part of premixed biphasic regimens. The two basal insulin analogues, glargine and detemir, developed by adjusting the isoelectric point and adding a fatty acid residue, respectively, have a protracted duration of action and a relatively smooth profile. Their pharmacokinetic and pharmacodynamic profiles have been assessed using euglycaemic clamp protocols. Both analogues have a longer duration of action, less of a peak of activity and a reduced variability with repeated injection. There is some evidence to suggest that detemir may have a slight hepatoselective effect. Clinical studies have shown a lower relative risk of hypoglycaemia and detemir appears to have a weight-sparing action. Insulin analogues represent a successful example of applied medical science. [source] Glycaemic status and cardiovascular disease in type 2 diabetes mellitus: re-visiting glycated haemoglobin targets for cardiovascular disease preventionDIABETES OBESITY & METABOLISM, Issue 6 2007Sherita H. Golden Cardiovascular disease (CVD) is the leading cause of death among people with type 2 diabetes. Recent attention has focused on chronic hyperglycaemia as an additional risk factor in people with diabetes since their excess CVD risk is not entirely explained by traditional cardiovascular risk factors. Clinical trials of intensive glucose control to reduce CVD events have been equivocal, but recent epidemiological studies have shown that HbAlc, a measure of chronic hyperglycaemia, predicts incident cardiovascular events. This review, which focuses on type 2 diabetes, summarizes (i) the epidemiological literature examining the relation between glycaemic status, as assessed by glycated haemoglobin (HbAlc) and CVD, (ii) the controversy regarding treatment goals for HbAlc in terms of preventing microvascular disease vs. macrovascular disease and (iii) on-going clinical trials of intensive glycaemic control for CVD prevention. [source] Inhaled insulin as adjunctive therapy in subjects with type 2 diabetes failing oral agents: a controlled proof-of-concept studyDIABETES OBESITY & METABOLISM, Issue 5 2006M. Hausmann Aim:, This controlled proof-of-concept study investigated inhaled insulin (INH) as adjunctive therapy to existing oral antidiabetic agents in subjects with type 2 diabetes. Methods:, Twenty-four subjects with type 2 diabetes [19 men and 5 women, 56.1 ± 6.6 years, body mass index 32.7 ± 4.2 kg/m2, glycosylated haemoglobin (HbA1c) 8.4 ± 0.8% (mean ± s.d.)] inadequately controlled by metformin and/or sulfonylureas were randomized to receive additional therapy with either INH administered preprandially using a metered-dose inhaler (MDI), or insulin glargine (GLA) injected subcutaneously at bedtime for 4 weeks. Both inhaled and injected insulin doses were titrated to predefined blood glucose (BG) targets. Results:, INH and GLA improved metabolic control to a similar extent. Mean daily BG decreased by 2.8 mmol/l in the INH group (p < 0.001) and by 2.4 mmol/l in the GLA group (p < 0.001). Accordingly, fasting BG (,2.7 vs. ,3.6 mmol/l for INH vs. GLA), preprandial- and 2-h postprandial BG, HbA1c (,1.23 vs. ,1.05%), body weight (,1.9 vs. ,2.3 kg) and serum fructosamine were similarly and significantly reduced in both groups (p < 0.05). Triglycerides decreased significantly with INH (,1.15 ,mol/l; p < 0.001) but not with GLA [,0.52 ,mol/l; not significant (NS)]. Incidence rates of adverse events did not differ significantly, and there were no indications of respiratory tract irritation. Conclusions:, In subjects with type 2 diabetes inadequately controlled by oral agents, preprandial administration of INH delivered by a MDI provided a comparable metabolic control to bedtime GLA and did not show any safety concerns during a 4-week treatment. These results warrant a more extensive investigation of preprandial treatment with INH in longer term studies. [source] Unlocking the opportunity of tight glycaemic controlDIABETES OBESITY & METABOLISM, Issue 2005Inhaled insulin: clinical efficacy Numerous attempts have been made to develop novel routes of insulin delivery that are both effective and tolerable. Of all the potential non-invasive delivery options, pulmonary delivery is the most clinically viable. Early studies demonstrate that the inhaled insulin is rapidly absorbed and is closer to biological insulin than standard subcutaneous insulin (SC). To date, inhaled insulin (Exubera®) has been clinically assessed in more than 3500 patients with type 1 or type 2 diabetes, some treated for more than 7 years. Several phase 3 studies of 24-week duration have demonstrated comparable glycosylated haemoglobin (HbA1c) control in patients with type 1 diabetes treated with Exubera® vs. SC insulin. Similar results have also been recorded in patients with type 2 diabetes. Furthermore, Exubera® has shown clinical superiority to oral agent regimens in patients with type 2 diabetes who failed to achieve their target HbA1c using lifestyle modification and oral agents. Exubera® was well tolerated and treatment satisfaction was high, with Exubera® being the preferred insulin therapy in all studies. The results of these trials, and others, suggest that Exubera® may be a valuable tool to help a wide variety of patients with type 1 or type 2 diabetes reach their recommended goals for glycaemic control, irrespective of their current therapy. [source] Lipids and lipoprotein(a) concentrations in Pakistani patients with type 2 diabetes mellitusDIABETES OBESITY & METABOLISM, Issue 5 2004S. S. Habib Aim:, The aim of the present study was to analyze serum lipoprotein(a) [Lp(a)] levels in Pakistani patients with type 2 diabetes mellitus (DM) and to find correlations between clinical characteristics and dyslipidaemias in these patients. Methods:, Fasting blood samples were analyzed for Lp(a), total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), glucose and glycosylated haemoglobin (HbA1c) in 68 Pakistani patients with type 2 DM and 40 non-diabetic healthy control subjects. Results:, Lp(a) levels were significantly raised in diabetics as compared to the control group. No correlation of Lp(a) was seen with age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting glucose. There was a positive correlation of BMI to SBP and DBP. There was a significant positive correlation between Lp(a) and total cholesterol and LDL-c. No correlation of Lp(a) was observed with HDL-c, triglycerides and glycosylated haemoglobin (HbA1c). Conclusion:, The present study led us to conclude that serum Lp(a) levels are significantly raised in type 2 DM and have a positive correlation with serum total and LDL-c levels. [source] Twice daily biphasic insulin aspart improves postprandial glycaemic control more effectively than twice daily NPH insulin, with low risk of hypoglycaemia, in patients with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 6 2003J. S. Christiansen Objective:, Biphasic insulin aspart 30 (BIAsp30) is a dual release formulation, containing 30% soluble and 70% protamine-crystallized insulin aspart. This study compared the glycaemic control and safety profiles achieved with either twice daily BIAsp30 or NPH insulin in patients with type 2 diabetes not optimally controlled by oral hypoglycaemic agents (OHAs), NPH insulin or a combination of both. Methods:, In this 16-week multinational, parallel-group, double-blind trial, 403 such patients were randomized to receive either BIAsp30 or NPH insulin immediately before breakfast and evening meals. OHAs were discontinued at randomization. Efficacy was assessed by glycosylated haemoglobin (HbA1c) and self-recorded daily 8-point blood glucose (BG) profiles. Hypoglycaemic and other adverse events were the chosen safety parameters. Results:, HbA1c concentration decreased by >0.6% (p < 0.0001 vs. baseline) in both groups, with metabolic control continuing to improve throughout the trial without reaching a stable level. Patients who switched from once or twice daily NPH monotherapy to twice daily BIAsp30 achieved a significantly greater reduction in HbA1c (0.78%) than those randomized to twice daily NPH insulin (0.58%; p = 0.03). BIAsp30 decreased mean daily postprandial glycaemic exposure to a greater extent than NPH insulin (mean difference = 0.69 mmol/l; p < 0.0001), reflecting greater decreases in the postbreakfast and postdinner increments (of 1.26 and 1.33 mmol/l, respectively), although postlunch increment was relatively increased (by 0.56 mmol/l). Despite the greater reduction in overall postprandial glycaemic exposure in the BIAsp30 group, the overall safety profile of BIAsp30 was equivalent to that of NPH insulin with <2% of patients experiencing major hypoglycaemia, and approximately 33% reporting minor hypoglycaemic episodes, in both groups. Conclusion:, Twice daily BIAsp30 reduced postprandial glucose exposure to a significantly greater extent than NPH insulin and was at least as effective at reducing HbA1c in patients with type 2 diabetes. Both insulins were well tolerated. In patients poorly controlled on OHAs or NPH alone, glycaemic control can be improved by switching to twice daily BIAsp30, without increasing hypoglycaemic risk. [source] Subclinical vascular alterations in young adults with type 1 diabetes detected by arterial tonometryDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 8 2009I. Barchetta Abstract Background Diabetes mellitus is characterized by a very high prevalence of atherosclerotic disease. Aims of this study were to determine arterial compliance parameters in type 1 diabetes (T1D) patients as an expression of early pre-clinical endothelial dysfunction and to evaluate the impact of glucose exposure parameters such as the duration of diabetes and glycosylated haemoglobin (HbA1c) on the risk of developing alterations in vascular compliance. Methods 23 patients with uncomplicated type 1 diabetes (mean age: 32.78 ± 9.06 years, mean disease duration: 10.78 ± 7.51 years, mean HbA1c levels: 7.7 ± 1.9) and 26 age- and sex-matched healthy subjects (mean age: 32.3 ± 8.51 years) were recruited. In these subjects, we evaluated arterial compliance by calibrated tonometry (HDI/PulsewaveÔ CR-2000). Parameters included the following: large artery elasticity (C1), small artery elasticity (C2), systemic vascular resistance (SVR) and total vascular impedance (TVI). Results Patients with longer duration of T1D (>10 years) showed significant alterations in C2 (4.97 ± 2.7 mL/mmHg × 100) and in SVR (1464.67 ± 169.16 dina × s × cm,5) when compared with both healthy individuals (C2: 8.28 ± 2.67 mL/mmHg × 100, p = 0.001; SVR: 1180.58 ± 151.55 dina × s × cm,5, p = 0.01) and patients with recent-onset disease (,10 years) (C2: 10.02 ± 3.6 mL/mmHg × 100, p < 0.001; SVR: 1124.18 ± 178.5 dina × s × cm,5, p < 0.000). Both disease duration and HbA1c independently predicted impaired arterial compliance. Conclusions Young adult T1D patients with no signs of disease complication have detectable vessel wall abnormalities, particularly of small arteries, suggestive of hyperglycaemia-related early endothelial dysfunction. Copyright © 2009 John Wiley & Sons, Ltd. [source] Glycemic risk factors of diabetic vascular complications: the role of glycemic variabilityDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2009Francesco Zaccardi Abstract Achieving adequate targets relatively to all risk factors is considered a standard of care for patients with diabetes mellitus. To date, current guidelines underline the importance of the ,glucose triad' (post-prandial glucose, fasting plasma glucose and glycated haemoglobin) as the three glycemic factors that should be controlled in diabetes care; however, several literature data show that optimizing glycemic control needs achieving a control of glycemic variations. The objective of the present work is reviewing biological and clinical data supporting the role of glycemic variability, its measurement and relationship with the three other well-known glycemic risk factors and evidencing the areas that need further investigation. At last, we propose a simple model that summarizes the ,glucose triad' plus the ,new' risk factor glycemic variability (the ,Pyramid of the Risk'). Copyright © 2009 John Wiley & Sons, Ltd. [source] Decline of neuroadrenergic bronchial innervation and respiratory function in type 1 diabetes mellitus: a longitudinal studyDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2007Raffaele Antonelli Incalzi Abstract Background and aim Type 1 diabetes mellitus complicated by autonomic neuropathy (AN) is characterized by depressed cholinergic bronchomotor tone and neuroadrenergic denervation of the lung. We explored the effects of AN on the rate of decline of pulmonary sympathetic innervation and respiratory function during a 5-year follow-up. Methods Twenty diabetic patients, 11 with AN, were enrolled in 1998 and then followed-up until 2003. During follow-up, glycosylated haemoglobin (HbA1c) was measured every 3 months. In 1998 and 2003 the patients underwent respiratory function tests and a ventilatory scintigraphic study of neuroadrenergic bronchial innervation using 123I-MIBG. Results During follow-up 4 patients, all with AN, were lost, and 1 developed AN. Forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) showed comparable rates of decrease in patients with and without AN. The yearly decline of forced expiratory volume in 1 s (FEV1) was about double the physiologic rate, in both AN and AN-free patients. The MIBG clearance significantly increased both in patients with AN (T1/2: 118.88 ± 30.14 min at baseline and 92.10 ± 24.52 min at the end of follow-up) and without AN (135.14 ± 17.09 min and 92.68 ± 13.52 min, respectively), indicating a rapidly progressive neuroadrenergic denervation. The rate of the neuroadrenergic denervation was inversely related to the severity of autonomic dysfunction at baseline (Spearman's rho , 0.62, p = 0.017). Neither respiratory function indexes nor MIBG clearance changes correlated with the overall HbA1c values. Conclusions Neuroadrenergic denervation of the lung parallels the decline of respiratory function indexes in diabetic patients both with and without AN and seems to be independent from the quality of glycemic control. Copyright © 2006 John Wiley & Sons, Ltd. [source] Age-related anthropometric remodelling resulting in increased and redistributed adiposity is associated with increases in the prevalence of cardiovascular risk factors in Chinese subjectsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2006G. Neil Thomas Abstract Background Ageing promotes increases in the prevalence of components of the metabolic syndrome, which obesity often underlies. Methods We report the relationship between ageing, obesity and other cardiovascular risk factors in 694 community-based Chinese subjects in gender-specific groups of three age ranges: 20.0,39.9 (young), 40.0,59.9 (middle-aged) and 60.0,79.9 (old-aged) years. Results Body mass index (BMI) values were similar in males in each age group, but waist and percentage body fat increased (6.6, and 39.5%, both p < 0.001, respectively), from young to old-age groups, as did blood pressure and glycated haemoglobin levels (all p < 0.001). In the females, increases (all p < 0.001) in percentage body fat (29.3%) were accompanied by greater increases in BMI (10.3%) and waist (19.2%) than the males. Blood pressure, glycated haemoglobin, total and LDL-cholesterol and triglyceride levels increased linearly with age (all p < 0.001). Conclusion Age-related increases in central adiposity and percentage body fat were associated with increasingly adverse cardiovascular risk factor profiles. Copyright © 2005 John Wiley & Sons, Ltd. [source] Therapeutic targets in the management of Type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S1 2002P. D. Home Abstract For historical reasons, diabetes has long been linked with blood and urine glucose control, partly because these were clearly linked to acute symptoms, and partly because glucose became measurable around 200 years ago. Today it is recognized that there is far more to diabetes than simply monitoring symptoms and blood glucose. Intensive management has an impact on the quality of life. Late complications have their own risk factors and markers. Monitoring and early detection of these risk factors and markers can lead to changes in treatment before tissue damage is too severe. Accordingly, professionals now find themselves monitoring a range of adverse outcomes, markers for adverse outcomes, risk factors and risk markers for microvascular and arterial disease, acute complications of therapy, and the care structures needed to deliver this. Adverse outcomes lend themselves to targets for complication control in populations, and markers of adverse outcomes (such as retinopathy and raised albumin excretion rate) in treatment cohorts. Surveillance systems will have targets for yearly recall and review of early complications. Metabolic (surrogate) outcomes can be monitored in individual patients, but monitoring is only of value in so far as it guides interventions, and this requires comparison to some intervention level or absolute target. Even for blood glucose control this is not easy, for conventional measures such as glycated haemoglobin have their own problems, and more modern approaches such as post-prandial glucose levels are controversial and less convenient to measure. In many people with type 1 diabetes targets for blood pressure, LDL cholesterol, and serum triglycerides will also be appropriate, and need to be part of any protocol of management. Copyright © 2002 John Wiley & Sons, Ltd. [source] Original Article: Treatment: Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trialDIABETIC MEDICINE, Issue 9 2010R. E. Ratner Diabet. Med. 27, 1024,1032 (2010) Abstract Aims, To evaluate the dose,response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes. Methods, Randomized, double-blind, placebo-controlled, parallel-group, 13 week study of 542 patients with Type 2 diabetes inadequately controlled [glycated haemoglobin (HbA1c) , 7.0 and < 9.0% (, 53 and < 75 mmol/mol)] on metformin (, 1000 mg/day) treated with subcutaneous lixisenatide doses of 5, 10, 20 or 30 ,g once daily or twice daily or placebo. The primary end-point was change in HbA1c from baseline to 13 weeks in the intent-to-treat population. Results, Lixisenatide significantly improved mean HbA1c from a baseline of 7.55% (59.0 mmol/mol); respective mean reductions for 5, 10, 20 and 30 ,g doses were 0.47, 0.50, 0.69 and 0.76% (5.1, 5.5, 7.5 and 8.3 mmol/mol), on once-daily and 0.65, 0.78, 0.75 and 0.87% (7.1, 8.5, 8.2 and 9.5 mmol/mol) on twice-daily administrations vs. 0.18% (2.0 mmol/mol) with placebo (all P < 0.01 vs. placebo). Target HbA1c < 7.0% (53 mmol/mol) at study end was achieved in 68% of patients receiving 20 and 30 ,g once-daily lixisenatide vs. 32% receiving placebo (P < 0.0001). Dose-dependent improvements were observed for fasting, postprandial and average self-monitored seven-point blood glucose levels. Weight changes ranged from ,2.0 to ,3.9 kg with lixisenatide vs. ,1.9 kg with placebo. The most frequent adverse event was mild-to-moderate nausea. Conclusions, Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin. Dose,response relationships were seen for once- and twice-daily regimens, with similar efficacy levels, with a 20 ,g once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio. This new, once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies. [source] Comparing risk profiles of individuals diagnosed with diabetes by OGTT and HbA1cThe Danish Inter99 studyDIABETIC MEDICINE, Issue 8 2010R. Borg Diabet. Med. 27, 906,910 (2010) Abstract Aims, Glycated haemoglobin (HbA1c) has been proposed as an alternative to the oral glucose tolerance test for diagnosing diabetes. We compared the cardiovascular risk profile of individuals identified by these two alternative methods. Methods, We assessed the prevalence of cardiovascular risk factors in individuals with undiagnosed diabetes according to the World Health Organization classification or by the newly proposed HbA1c level , 6.5% among 6258 participants of the Danish Inter99 study. Receiver operating curve analysis assessed the ability of fasting: 2-h plasma glucose and HbA1c to distinguish between individuals at high and low risk of ischemic heart disease, predicted by the PRECARD program. Results, Prevalence of undiagnosed diabetes was 4.1% [95% confidence interval (CI) 3.7,4.7%] by the current oral glucose tolerance test definition, whereas 6.6% (95% CI 6.0,7.2%) had diabetes by HbA1c levels. HbA1c -defined individuals were relatively older with higher proportions of men, smokers, lipid abnormalities and macro-albuminuria, but they were leaner and had lower blood pressure. HbA1c was better than fasting- and 2-h plasma glucose at distinguishing between individuals of high and low predicted risk of ischaemic heart disease; however, the difference between HbA1c and fasting- and 2-h plasma glucose was not statistically significant. Conclusions, Compared with the current oral glucose tolerance test definition, more individuals were classified as having diabetes based on the HbA1c criteria. This group had as unfavourable a risk profile as those identified by the oral glucose tolerance test. [source] | ||||||||||||||||||||||||||||||||||||||||||||||