This paper concludes a review of the contribution of information technology to diabetes care. The role of decision support tools for planning insulin therapy using various clinical algorithms, knowledge-based approaches and interactive simulations is discussed, and certain telemedicine approaches to therapy are considered. The validation and clinical evaluation of these tools is reviewed, as is the likely impact of the routine clinical application of implantable/non-invasive blood glucose monitoring devices. Finally, the application of computers as leaching tools is considered, and ways in which such educational approaches might be applied for disseminating the benefits of the Diabetes Control and Complications Trial more widely are discussed.

The purpose of this paper is to report a survey of 1,360 downloads of the AIDA interactive educational diabetes simulator. AIDA is a diabetes computer program which permits the interactive simulation of plasma insulin and blood glucose profiles for educational, demonstration and self-learning purposes. It has been made freely available, without charge, on the Internet as a non-commercial contribution to continuing diabetes education. Since its launch in 1996 over 74,000 visits have been logged at the AIDA Website – http://www.2aida.org – and over 20,000 copies of the AIDA program have been downloaded free-of-charge. This report documents a preliminary survey of downloaders of the software. The intended goals of the study were: (i) to establish the feasibility of using the Internet for auditing and surveying diabetes software users; (ii) to identify the proportion of patients with diabetes and their relatives who are actually making use of the program; and (iii) to establish certain technical details about downloaders’ computer setups to facilitate the distribution of upgrades to the software. Results: The Internet-based survey methodology was found to be robust and reliable. 1,360 responses were received over an 8 month period (from November 1999 to July 2000). During the corresponding period 3,821 actual downloads of the software were independently logged at the Website – giving a response rate to this survey of 35.6%. Responses were received from participants in 67 countries – although over half of these (n=730, 54%) originated from the USA and UK. 762 responses (56%) were received from patients with diabetes and 184 (13.5%) from relatives of patients, with lesser numbers from doctors, students, diabetes educators, nurses, pharmacists, and other end users. Useful technical information about computers and operating systems being used were also obtained. This study has established the feasibility of using the Internet to survey, at no real cost, a large number of medical software downloaders/users. In addition it has yielded interesting data in terms of who are the main downloaders of the AIDA program, and has also provided technical (computer) information which has aided the recent release of a freeware upgrade to the software

In 1996 an interactive educational diabetes simulator called AIDA was released without charge on the Internet as a non-commercial contribution to continuing diabetes education. Over the past 4+ years over 74,000 people have visited the AIDA Web pages at http://www.2aida.org and over 20,000 copies of the program have been downloaded from there free-of-charge. This article builds on the experience gained from the AIDA development, and the World Wide Web distribution of the software, and highlights some of the problems which users have reported with the program. An updated release of the software (AIDA v4.3) is described and the method applied for modelling glycosylated haemoglobin (HbA1c) levels within this new version of AIDA is documented. An overview is provided of the trialling and beta-testing of this latest release of the program, and the general concept of a 'virtual diabetic patient' that provides an electronic representation of a patient with diabetes--and which can be used for self-learning/teaching/demonstration purposes--is highlighted.

In previous "Diabetes Information Technology & WebWatch" columns, various user experience with an interactive educational "virtual diabetes patient" simulator called AIDA have been documented. The simulator is available free of charge from http://www.2aida.org on the Web, and user comments that have been received to date about the program have highlighted some of the many and varied ways in which a range of people have been applying the diabetes simulations in their own particular situations and practices. Inevitably, up to now, a great deal of attention has focused on use by individuals with diabetes and their relatives, as well as by health-care professionals such as diabetologists/endocrinologists and diabetes educators. However, an important group of health-carers involved in the provision of day-to-day care for many people with diabetes are primary care physicians (general practitioners). The current "Diabetes Information Technology & WebWatch" column addresses this area, overviewing a workshop which was held in September 2000 in Italy to gain experience with application of the AIDA diabetes simulation approach as a teaching tool for general practitioners (GPs). Feedback obtained from participants attending the workshop was very positive, with GPs reporting the simulation approach to be both of interest and use. Further workshops involving other healthcare professionals--in particular, nurses--are planned.

663 This “Diabetes Information Technology & WebWatch” column continues the diabetes simulation theme from previous issues and overviews various user experience with the AIDA v4 interactive educational freeware diabetes simulator. 1AIDA v4 is a diabetes computer program which permits the interactive simulation of plasma insulin and blood glucose (BG) profiles for educational, demonstration, and self-learning purposes. It has been made freely available, without charge, via the Web as a noncommercial contribution to continuing diabetes education. Since its Internet launch in 1996 over 55,000 visits have been logged at the AIDA Web site— http://www.2aida.org—and over 17,200 copies of the program have been downloaded, free of charge. While these statistics may appear impressive, they do not tell the personal story of how people have been making use of the software, and what they actually think about it. In this respect this column documents some of the independent user comments about the program sent in spontaneously via electronic mail (email) by patients with diabetes and their relatives, as well as by healthcare professionals. Comments posted to diabetes newsgroups and list servers, as well as a selection of those which have been found at other, linked diabetes Web sites are also highlighted.

This paper overviews the Internet release of AIDA, a freeware interactive educational diabetes simulator. Since its release on the World Wide Web as a non-commercial contribution to continuing diabetes education over 14,000 people have visited the AIDA Web site--http:/(/)www.diabetic.org.uk/aida.htm--and over 5000 copies of the program have been downloaded, without charge. User responses thus far have been very encouraging. Example feedback and clinical experience reported by two insulin-dependent (type 1) diabetic patients, a patient's carer, the father of a diabetic teenager, a diabetes doctor and nurse educator, an endocrinologist and a postgraduate educator are presented. While such anecdotal, qualitative assessments are worthwhile and form a necessary step in the overall evaluation process--they are clearly subjective in nature and fully recognised as such. Given this, definitive outcome measures are highlighted as being required for the next stage in the evaluation process, and various objective evaluation criteria are proposed. A general protocol for the evaluation of interactive educational simulation tools, like AIDA, with patients is described and the concept of applying this in multiple centres--as a way of increasing study sample sizes--is discussed. It is highlighted that such a protocol could also be used to objectively compare a number of different interactive educational diabetes simulators. Clinicians who are interested in collaborating by enrolling patients into such a study are invited to contact the author, by email, at aida@globalnet.co.uk

This article critically appraises selected clinically related papers that recently appeared in a two-part Special Issue of Medical Informatics, the official journal of the European Federation for Medical Informatics, This has been devoted to the application of computers in clinical diabetes care, The 15 papers included in the Special Issues cover database systems (including telemedicine and smart-card based applications), algorithmic-based systems, decision-support prototypes, the use of models, and educational software, In this article the computing background to the work is overviewed, before the clinical need and potential cost-benefits of utilising information technology in clinical diabetes care are highlighted, The DIAMOND, DIABCARD, DIABTel, HumaLink, AIDA, 'Packy & Marlon', and 'Learning Diabetes' systems are reviewed, Concerns over evaluation methodologies are raised and it is suggested that such issues need to be addressed, before programs like these will see widespread utilisation and clinical acceptance, Although the Medical Informatics Special Issues should not be considered as in any way comprehensive in their coverage of clinical diabetes computing - it is hoped that the compilation of papers provided there - along with this critical appraisal - may offer a useful source of novel ideas - as well as, perhaps, a starting point for future research. (C) 1997, Editrice Kurtis.

Diabetic patients are at an increased risk of cardiovascular disease, however, some patients do not develop cardiovascular sequelae, whereas others will have devastating complications.1Barrett-Connor E Wingard DL Sex differential in ischemic heart disease mortality in diabetics: a prospective population-based study.Am J Epidemiol. 1983; 118: 489-496PubMed Google Scholar Since there are many practical lifestyle and pharmacological interventions that can be directed at patients with an increased risk of vascular complications, the early identification of these patients has long been of interest to clinicians. Various biochemical tests, such as the measurement of serum lipid and lipoprotein concentrations and microalbuminuria, have been proposed to help identify these at-risk patients. There is also increased interest in the use of non-invasive biophysical measurements of the vasculature to complement biochemical predictors, and several biophysical techniques are available. These range from the simple—ie, ankle/brachial blood-pressure ratio—to the more complex—ie, magnetic resonance (MR) coronary angiography and MR plaque characterisation. In diabetic patients, the ankle/brachial blood-pressure ratio may be of limited use because medial calcification of the vasculature can lead to falsely high readings. MR techniques are still very much under development. Although non-invasive measurements from different vessels may be associated with changes in the coronary vasculature, the pathophysiological mechanisms involved may not mirror the processes taking place in coronary vessels. Therefore, the use of measurements with clearly defined pathophysiological significance may be of greater clinical benefit than surrogates which only happen to correlate with the presence of coronary artery disease. This review focuses on three non-invasive vascular measurement techniques (figure 1)—carotid artery intima-media thickness (IMT), aortic pulse wave velocity (PWV) and arterial stiffness, and brachial artery flow-mediated dilatation (FMD) during reactive hyperaemia. We provide an overview of the data from the use of each of these techniques in diabetic patients, as well as highlighting areas where further research is needed. IMT is the distance between the leading edges of a characteristic double-line pattern seen in longitudinal B-mode ultrasound images of the artery wall (figure 1). IMT has an interobserver coefficient of variation of about 10%.2Salonen R Haapanen A Salonen JT Measurement of intima-media thickness of common carotid arteries with high-resolution B-mode ultrasonography: inter- and intra-observer variability.Ultrasound Med Biol. 1991; 17: 225-230Summary Full Text PDF PubMed Scopus (212) Google Scholar Measurement of the far wall IMT of the common carotid artery has become an important endpoint of atherosclerosis in epidemiological studies and cardiovascular clinical trials. To measure IMT reliably, high-resolution ultrasound must be used. A 7·5–10·0 MHz transducer typically provides an axial resolution of 0·15–0·2 mm, which limits the smallest IMT that can be measured to this range. Individual measurements of IMT are also limited by the pixel dimension of the digitised image, which is about 0·05 mm. Multicentre trials that used highly standardised protocols and carefully trained sonographers and readers were able to detect group (n=200) differences in progression rates of IMT measurements as small as 0·01 mm per year from several anatomical sites (common carotid artery, carotid bifurcation, and internal carotid artery) during 3 years' follow-up.3Furberg CD Adams HP Applegate WB et al.Effect of lovastatin on early carotid atherosclerosis and cardiovascular events.Circulation. 1994; 90: 1679-1687Crossref PubMed Scopus (825) Google Scholar The small differences in the mean annual progression rates of IMT—which are substantially less than both the axial resolution and the pixel dimension—are derived from statistical analyses of the changes in group mean values over time. To achieve these results, and to keep measurement variability to a minimum, both personnel and equipment must be routinely monitored for consistency of performance. In a randomly selected, population-based sample of people aged 45, the mean far wall IMT in the common carotid artery was about 0·6 mm (5th-95th percentile range 0·4–0·8 mm).4Howard G Sharrett AR Heiss G et al.Carotid artery intimal-medial thickness distribution in general populations as evaluated by B-mode ultrasound.Stroke. 1993; 24: 1297-1304Crossref PubMed Scopus (646) Google Scholar The rates of change in IMT with age in cross-sectional studies have been calculated to be about 0·01 mm per year in the general population and 0·03–0·06 mm per year in patients with ischaemic heart disease. Espeland and colleagues5Espeland MA Craven TE Riley WA Corson J Romont A Furberg CD Reliability of longitudinal ultrasonographic measurements of carotid intimal-medial thicknesses.Stroke. 1996; 27: 480-485Crossref PubMed Scopus (119) Google Scholar have also established, by standard methods, the interval needed to obtain reliable IMT progression rates in individuals. Based on this analysis, 6 or more years of follow-up are required to define IMT progression rates for an individual.5Espeland MA Craven TE Riley WA Corson J Romont A Furberg CD Reliability of longitudinal ultrasonographic measurements of carotid intimal-medial thicknesses.Stroke. 1996; 27: 480-485Crossref PubMed Scopus (119) Google Scholar A general population study of more than 14 000 men and women aged 45–64 years in the Atherosclerosis Risk in Communities (ARK)6Folsom AR Eckfeldt JH Weitzman S et al.Relation of carotid artery wall thickness to diabetes mellitus, fasting glucose and insulin, body size, and physical activity.Stroke. 1994; 25: 66-73Crossref PubMed Scopus (397) Google Scholar cohort found the mean IMT to be about 0·08 mm greater in diabetic than in non-diabetic individuals—after adjustment for age, sex, race, smoking, and body-mass index. Adjusted mean IMT was 0·02 mm greater in non-diabetic individuals with hyperglycaemia, and there was also a small increase in IMT in people with raised serum insulin concentrations. Agewall et al7Agewall S Fagerberg B Attvall S Wendelhag I Urbanavicius V Wikstrand J Carotid artery wall intima-media thickness is associated with insulin-mediated glucose disposal in men at high and low coronary risk.Stroke. 1995; 26: 956-960Crossref PubMed Scopus (117) Google Scholar studied insulin sensitivity and IMT in hypertensive men aged 57–77 years with one or more traditional cardiovascular risk factors, compared with age-matched controls with no risk factors. IMT was inversely related to insulin sensitivity in both groups and a possible association between reduced insulin sensitivity and atherogenesis was suggested. In a multiethnic study of 1400 people, this inverse association was also found in both Hispanic and white people but not in black people—suggesting ethnic modulation of this association.8Howard G O'Leary DH Zaccaro D et al.Insulin sensitivity and atherosclerosis.Circulation. 1996; 93: 1809-1817Crossref PubMed Scopus (646) Google Scholar In a study of male hypertensive patients with or without non-insulin-dependent diabetes mellitus (NIDDM) aged 50–72 years, albuminuria was positively associated with increased IMT in the NIDDM patients, whereas no relation was found in the non-diabetic patients.9Agewall S Wikstrand J Ljungman S Fagerberg B Urinary albumin excretion is associated with the intima-media thickness of the carotid artery in hypertensive males with non-insulin-dependent diabetes mellitus.J Hypertens. 1995; 13: 463-469Crossref PubMed Scopus (58) Google Scholar Willey et al10Willey KA Kidd JF Harris JP Xu ZR Yue DK Albuminuria is an independent predictor of carotid intima-media thickness and atherosclerosis in NIDDM patients.Diabetes Care. 1995; 18: 1502-1503Crossref PubMed Scopus (16) Google Scholar also found albuminuria to be an independent predictor of increased IMT in NIDDM; by comparison with population-derived IMT data6Folsom AR Eckfeldt JH Weitzman S et al.Relation of carotid artery wall thickness to diabetes mellitus, fasting glucose and insulin, body size, and physical activity.Stroke. 1994; 25: 66-73Crossref PubMed Scopus (397) Google Scholar they concluded that patients with both diabetes and albuminuria are 26 years more advanced in the atherosclerotic process (as assessed by IMT) than the general non-diabetic population. Although Kawamori and workers11Kawamori R Yamasaki Y Matsushima H et al.Prevalence of carotid atherosclerosis in diabetic patients.Diabetes Care. 1992; 15: 1290-1294Crossref PubMed Scopus (286) Google Scholar have reported an association between IMT and diabetes duration, this observation has not been made in other studies, such as the multicentre Insulin Resistance Atherosclerosis Study.12Wagenknecht LE D'Agostino R Savage PJ O'Leary DH Saad MF Haffner SM Duration of diabetes and carotid wall thickness.Stroke. 1997; 28: 999-1005Crossref PubMed Scopus (123) Google Scholar Furthermore, no correlation was found between glycated haemoglobin (HbA1c and IMT.11Kawamori R Yamasaki Y Matsushima H et al.Prevalence of carotid atherosclerosis in diabetic patients.Diabetes Care. 1992; 15: 1290-1294Crossref PubMed Scopus (286) Google Scholar Patients with insulin-dependent diabetes mellitus (IDDM) have IMT values 0·08–0·16 mm larger than age-matched non-diabetic individuals.13Yamasaki Y Kawamori R Matsushima H et al.Atherosclerosis in carotid artery of young IDDM patients monitored by ultrasound high-resolution B mode imaging.Diabetes. 1994; 43: 634-639Crossref PubMed Scopus (204) Google Scholar Long-term intensified insulin therapy in IDDM in the Stockholm Diabetes Intervention Study14Jensen-Urstad KJ Reichard PG Resfors JS Lindblad LEL Jensen-Urstad MT Early atherosclerosis is retarded by improved long-term blood glucose control in patients with IDDM.Diabetes. 1996; 45: 1253-1258Crossref PubMed Google Scholar has been associated with smaller mean IMTs. However, in a cohort of 1326 patients from the Diabetes Control and Complications Trial,15Zinman B Cleary P O'Leary D Orchard T The EDIC Study GroupThe effect of intensive diabetes treatment on carotid artery wall thickness in the epidemiology of diabetes interventions and complications.Diabetes. 1996; 45 (abstr): 692Google Scholar no significant differences in IMT were observed between the intensively and conventionally treated groups after an average 6·5 years' follow-up, and the IMT values from these two groups were similar to those of age-matched non-diabetic individuals. IMT provides information about vessel-wall anatomy only. Other important aspects of atherosclerosis related to vessel function, such as wall composition or stiffness, can also be studied in diabetic populations with other non-invasive techniques. The combination of IMT with measurements of arterial stiffness and PWV,14Jensen-Urstad KJ Reichard PG Resfors JS Lindblad LEL Jensen-Urstad MT Early atherosclerosis is retarded by improved long-term blood glucose control in patients with IDDM.Diabetes. 1996; 45: 1253-1258Crossref PubMed Google Scholar, 16Salomaa V Riley W Kark JD Nardo C Folsom AR Non-insulin-dependent diabetes mellitus and fasting glucose and insulin concentrations are associated with arterial stiffness indexes.Circulation. 1995; 91: 1432-1443Crossref PubMed Scopus (523) Google Scholar may provide unique information about vascular disease processes in diabetes. Arterial stiffness can be non-invasively assessed by either direct or indirect methods. Direct techniques involve the measurement of the relative change in arterial diameter and pressure during the cardiac cycle. The vessel diameter measurements can be done ‘by eye’, but the coefficient of variation for this method ranges up to 23% (on transthoracic echo-cardiograms) and 34% (on MR images).17Lehmann ED Pulse wave velocity as a marker of vascular disease.Lancet. 1996; 348: 744Summary Full Text Full Text PDF Google ScholarLehmann ED Pulse wave velocity as a marker of vascular disease.Lancet. 1996; 348: 1587Summary Full Text Full Text PDF PubMed Google Scholar By contrast a coefficient of variation of about 7% occurs with the use of a phase-locked echo-tracking device.18Lanne T Stale H Bengtsson D et al.Noninvasive measurement of diameter changes in the distal abdominal aorta in man.Ultrasound Med Biol. 1992; 18: 451-457Summary Full Text PDF PubMed Scopus (91) Google Scholar The critical requirements for these methods are the accurate measurement of the change in arterial diameter caused by the pulse pressure and determination of the blood pressure at the site of the diameter measurement. Indirect measurements are based on the PWV—ie, the time that it takes the pulse wave to travel a given distance along the vasculature (figure 1). These measurements can be done non-invasively in the aortic or aorto-iliac pathways with doppler ultrasound (coefficient of variation <10%),19Lehmann ED Hopkins KD Gosling RG Aortic compliance measurements using Doppler ultrasound: in vivo biochemical correlates.Ultrasound Med Biol. 1993; 19: 683-710Summary Full Text PDF PubMed Scopus (105) Google Scholar applanation tonometry20Kelly R Hayward C Ganis J Daley J Avolio A O'Rourke M Noninvasive registration of the arterial pressure pulse waveform using high-fidelity applanation tonometry.J Vasc Med Biol. 1989; 1: 142-149Google Scholar or MR imaging.21Mohiaddin RH Firmin DN Longmore DB Age-related changes of human aortic flow wave velocity measured noninvasively by magnetic resonance imaging.J Appl Physiol. 1993; 74: 492-497PubMed Google Scholar The critical factors are the precise measurement of the pulse transit time and the path length. The PWV is increased in stiffer arteries. Data from necropsy studies in animals22Farrar DJ Bond MG Riley WA Sawyer JK Anatomic correlates of aortic pulse wave velocity and carotid artery elasticity during atherosclerosis progression and regression in monkeys.Circulation. 1991; 83: 1754-1763Crossref PubMed Scopus (186) Google Scholar and human beings23Wada T Kodaira K Fujishiro K et al.Correlation of ultrasound-measured common carotid artery stiffness with pathological findings.Arterioscler Thromb. 1994; 14: 479-482Crossref PubMed Google Scholar show that the atherosclerotic involvement of vessels correlates with arterial stiffness assessed non-invasively before death. An association between aortic stiffness and the degree of coronary artery disease assessed at coronary angiography has also been reported.24Hirai T Sasayama S Kawasaki T Yagi S Stiffness of systemic arteries in patients with myocardial infarction.Circulation. 1989; 80: 78-86Crossref PubMed Scopus (685) Google Scholar These data suggest a possible role for such non-invasive measurements, as markers of atherosclerotic load or coronary vascular risk. This suggestion is supported by evidence that aortic stiffness is an important determinant of both left-ventricular function and coronary blood flow. Aortic PWV also correlates with the ratio of left-ventricular wall thickness to radius in both hypertensive and normotensive people.25Dahan M Paillole C Ferreira B Gourgon R Doppler echo-cardiographic study of the consequences of aging and hypertension on the left ventricle and aorta.Eur Heart J. 1990; 11: 39-45Crossref PubMed Google Scholar In animals, increasing aortic stiffness aggravates myocardial ischaemia when coronary blood flow is impaired—possibly by decreasing the inverse pressure gradient that leads to coronary filling.26Watanabe H Ohtsuka S Kakihana M Sugishita Y Decreased aortic compliance aggravates subendocardial ischaemia in dogs with stenosed coronary artery.Cardiovasc Res. 1992; 26: 1212-1218Crossref PubMed Scopus (55) Google Scholar This latter effect would be especially important when there are coronary artery flow-limiting lesions. NIDDM patients have stiffer aortas—ie, higher PWVs—than non-diabetic individuals.19Lehmann ED Hopkins KD Gosling RG Aortic compliance measurements using Doppler ultrasound: in vivo biochemical correlates.Ultrasound Med Biol. 1993; 19: 683-710Summary Full Text PDF PubMed Scopus (105) Google Scholar, 27Airaksinen KEJ Salmela PI Linnaluoto MK Ikäheimo MJ Ahola K Ryhänen LJ Diminished arterial elasticity in diabetes: association with fluorescent advanced glycosylation end products in collagen.Cardiovasc Res. 1993; 27: 942-945Crossref PubMed Scopus (171) Google Scholar, 28Wahlqvist ML Lo CSM Myers KA Simpson RW Simpson JM Putative determinants of arterial wall compliance in NIDDM.Diabetes Care. 1988; 11: 787-790Crossref PubMed Scopus (52) Google Scholar, 29Wright JS Doppler ultrasound measurement of aortic compliance in diabetic patients and community controls.in: 2nd edn. PhD Thesis. University of London, London1991Google Scholar, 30Amar J Chamontin B Pelissier M et al.Influence of glucose metabolism on nyethemeral blood pressure variability in hypertensives with an elevated waist-hip ratio.Am J Hypertens. 1995; 8: 426-428Crossref PubMed Scopus (31) Google Scholar In one study of newly diagnosed NIDDM patients, the mean aortic PWV was 13·3 m/s in the diabetic group and 9·5 m/s in controls.30Amar J Chamontin B Pelissier M et al.Influence of glucose metabolism on nyethemeral blood pressure variability in hypertensives with an elevated waist-hip ratio.Am J Hypertens. 1995; 8: 426-428Crossref PubMed Scopus (31) Google Scholar One explanation of this finding may be the non-enzymatic glycosylation of matrix proteins caused by chronic hyperglycaemia. In-vitro glycosylation of collagen and elastin, and accumulation of advanced glycosylation end-products, has been shown to increase vessel stiffness.31Chappey O Dosquet C Wautier MP Wautier JL Advanced glycation end products, oxidant stress and vascular lesions.Eur J Clin Invest. 1997; 27: 97-108Crossref PubMed Scopus (208) Google Scholar Aortic PWV measurements in matched groups of diabetic and non-diabetic patients before coronary artery bypass grafting showed that the diabetic patients had stiffer aortas than those without diabetes.27Airaksinen KEJ Salmela PI Linnaluoto MK Ikäheimo MJ Ahola K Ryhänen LJ Diminished arterial elasticity in diabetes: association with fluorescent advanced glycosylation end products in collagen.Cardiovasc Res. 1993; 27: 942-945Crossref PubMed Scopus (171) Google Scholar Aortic samples obtained at the time of surgery showed a positive correlation between collagen-linked fluorescence, a marker of advanced glycosylation end products, and aortic PWV in the diabetic patients but not in the non-diabetic controls, which suggests that the diabetic state increases arterial stiffness.27Airaksinen KEJ Salmela PI Linnaluoto MK Ikäheimo MJ Ahola K Ryhänen LJ Diminished arterial elasticity in diabetes: association with fluorescent advanced glycosylation end products in collagen.Cardiovasc Res. 1993; 27: 942-945Crossref PubMed Scopus (171) Google Scholar Data from Oxlund et al32Oxlund H Rasmussen LM Andreassen TT Heickendorff L Increased aortic stiffness in patients with type I (insulin-dependent) diabetes mellitus.Diabetologia. 1989; 32: 748-752Crossref PubMed Scopus (117) Google Scholar support this suggestion; they found changes in arterial connective tissue and abnormal arterial biophysical properties in aortic necropsy specimens from IDDM patients independent of atherosclerosis. Similarly, Monnier and colleagues33Monnier VM Vishwanath V Frank KE Elmets CA Dauchot P Kohn RR Relation between complications of type I diabetes mellitus and collagen-linked fluorescence.N Engl J Med. 1986; 314: 403-408Crossref PubMed Scopus (527) Google Scholar observed a positive relation between aortic PWV and collagen-linked fluorescence. Aortic PWV also correlated with the severity of independently assessed diabetic complications—suggesting that non-invasive measurements may offer an indirect marker of long-term glycaemic control. Glycaemia is a prominent metabolic abnormality associated with diabetes that may be implicated as a cause of increased arterial stiffness. However, it is not the only metabolic abnormality. In the Bogalusa Heart Study,34Riley WA Freedman DS Higgs NA Barnes RW Zingraf SA Berenson GS Decreased arterial elasticity associated with cardiovascular disease risk factors in the young.Arteriosclerosis. 1986; 6: 378-386Crossref PubMed Google Scholar children with a positive parental history of diabetes had stiffer arteries than children without such a parental history. A similar result was reported in young non-diabetic adults with a positive family history of NIDDM compared with controls without such a history; the positive family history group had higher fasting glucose and insulin concentrations.35Hopkins KD Lehmann ED Jones RL Turay RC Gosling RG A family history of NIDDM is associated with decreased aortic distensibility in normal healthy young adult subjects.Diabetes Care. 1996; 19: 501-503Crossref PubMed Scopus (67) Google Scholar A causative link between glycaemia and vessel stiffness was also suggested by Wright,29Wright JS Doppler ultrasound measurement of aortic compliance in diabetic patients and community controls.in: 2nd edn. PhD Thesis. University of London, London1991Google Scholar who studied 494 patients (340 with NIDDM) and found that for any given age and blood pressure value, aortic PWV (stiffness) increased with abnormal glucose-tolerance status (assessed by an oral glucose-tolerance test) and diabetes duration. Wahlqvist et al28Wahlqvist ML Lo CSM Myers KA Simpson RW Simpson JM Putative determinants of arterial wall compliance in NIDDM.Diabetes Care. 1988; 11: 787-790Crossref PubMed Scopus (52) Google Scholar also studied the relation between aortic PWV and biochemical variables in non-diabetic and NIDDM patients, and found that aortic stiffness was best predicted by the area under the glucose-tolerance curve and age.28Wahlqvist ML Lo CSM Myers KA Simpson RW Simpson JM Putative determinants of arterial wall compliance in NIDDM.Diabetes Care. 1988; 11: 787-790Crossref PubMed Scopus (52) Google Scholar In a subset of the ARIC cohort,16Salomaa V Riley W Kark JD Nardo C Folsom AR Non-insulin-dependent diabetes mellitus and fasting glucose and insulin concentrations are associated with arterial stiffness indexes.Circulation. 1995; 91: 1432-1443Crossref PubMed Scopus (523) Google Scholar glucose and insulin synergistically contributed to the increase in arterial stiffness seen With increasing blood glucose concentrations. Ryden Ahlgren and colleagues36Ryden Ahlgren A Länne T Wollmer P Sonesson B Hansen E Sundkvist G Increased arterial stiffness in women, but not in men, with IDDM.Diabetologia. 1995; 38: 1082-1089Crossref PubMed Scopus (87) Google Scholar observed stiffer carotid arteries and aortas in women, but not men, with IDDM than in non-diabetic individuals; similar sex-specific results have been found for aortic PWV in patients with NIDDM.37Lehmann ED Hopkins KD Gosling RG Increased aortic stiffness in women with NIDDM.Diabetologia. 1996; 39: 870-871Crossref PubMed Scopus (21) Google Scholar Diabetes seems to decrease the protective effect female sex confers against cardiovascular disease,1Barrett-Connor E Wingard DL Sex differential in ischemic heart disease mortality in diabetics: a prospective population-based study.Am J Epidemiol. 1983; 118: 489-496PubMed Google Scholar and these data suggest that increased arterial stiffness in diabetic women, which is greater than that seen in diabetic men, may account for some of this difference. However, correlations from cross-sectional studies cannot prove causality, for which longitudinal and interventional studies are needed. Farrar et al22Farrar DJ Bond MG Riley WA Sawyer JK Anatomic correlates of aortic pulse wave velocity and carotid artery elasticity during atherosclerosis progression and regression in monkeys.Circulation. 1991; 83: 1754-1763Crossref PubMed Scopus (186) Google Scholar have shown in animals that atherosclerotic regression can be reliably monitored by non-invasive aortic PWV measurements—an important feature for long-term studies. Aminognanidine, which decreases advanced glycosylation end-product formation, also reduced arterial stiffness in diabetic rats.38Huijberts MS Wolffenbuttel BH Boudier HA et al.Aminoguanidine treatment increases elasticity and decreases fluid filtration of large arteries from diabetic rats.J Clin Invest. 1993; 92: 1407-1411Crossref PubMed Scopus (142) Google Scholar In the Stockholm Diabetes Intervention Study,14Jensen-Urstad KJ Reichard PG Resfors JS Lindblad LEL Jensen-Urstad MT Early atherosclerosis is retarded by improved long-term blood glucose control in patients with IDDM.Diabetes. 1996; 45: 1253-1258Crossref PubMed Google Scholar IDDM patients who had 10 years of intensive insulin treatment had both better glycaemic control and less stiff arteries (mean β-stiffness index 5·1 [SE 0·31) than the patients who received conventional insulin therapy (6·9 [0·6], p=0·01). Patients with higher HbA1c values also had stiffer arteries (figure 2).14Jensen-Urstad KJ Reichard PG Resfors JS Lindblad LEL Jensen-Urstad MT Early atherosclerosis is retarded by improved long-term blood glucose control in patients with IDDM.Diabetes. 1996; 45: 1253-1258Crossref PubMed Google Scholar Collectively, these data suggest that arterial stiffness/PWV measurements may be useful to non-invasively monitor the effects of therapeutic interventions. FMD may be induced by reactive hyperaemia after vessel occlusion and release. Increased blood flow raises shear stress at the vessel wall. This change seems to be detected by endothelial ‘mechanosensors’ and, in the healthy artery, leads to the production of vasodilatators such as nitric oxide by the endothelium. The dilatation after the flow increases (eg, diameter increase in the brachial artery from 3·7 mm to 4·1 mm) is often expressed as the mean (SD) percentage change in diameter (eg, 11 [3]%). Most of this dilatation can be blocked by L-NG-monomethylarginine (L-NMMA)—a specific antagonist of nitric oxide synthase—which indicates that FMD is mediated by nitric oxide and therefore is endothelium dependent.39Joannides R Haefeli WE Linder L et al.Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo.Circulation. 1995; 91: 1314-1319Crossref PubMed Scopus (1404) Google Scholar By contrast, the percentage change in vessel diameter after sublingual glyceryl trinitrate a smooth-muscle relaxant—is deemed ‘endothelium independent’.40Luscher TF Noll G Endothelial function as an end-point in interventional trials: concepts, methods and current data.J Hypertens. 1996; 14: S111-S119Crossref Google Scholar FMD is often interpreted as ‘endothelial dysfunction’ when it is decreased out of proportion to the dilator response to glyceryl trinitrate. Early studies used B-mode ultrasound to measure FMD (coefficient of variation <10%),41Celermajer DS Sorensen KE Gooch VM et al.Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.Lancet. 1992; 340: 1111-1115Summary Full Text PDF PubMed Scopus (4041) Google Scholar but more recently phase-locked echo-tracking devices have been employed. The relative change in brachial artery blood flow can also be measured with doppler ultrasound. Since endothelial injury is an early event in atherogenesis, Ross42Ross R The pathogenesis of atherosclerosis: a perspective for the 1990s.Nature. 1993; 362: 801-809Crossref PubMed Scopus (9868) Google Scholar has suggested that endothelial dysfunction may precede the development of structural changes in the vessel wall. For example, an impaired FMD—ie, a 1·5 [2]% diameter change—has been reported in children as young as 7 years old with hypercholesterolaemia.43Sorensen KE Celermajer DS Georgakopoulos D Hatcher G Betteridge DJ Deanfield JE Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level.J Clin Invest. 1994; 93: 50-55Crossref PubMed Scopus (530) Google Scholar Furthermore, in young adults, impaired FMD is associated with the same risk factors known to predispose to atherosclerosis and its complications (eg, tobacco smoke exposure, hypercholesterolaemia, and diabetes mellitus).44Celermajer D Sorensen K Bull C Robinson J Deanfield J Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction.J Am Coll Cardiol. 1994; 24: 1468-1474Summary Full Text PDF PubMed Scopus (1107) Google Scholar A large study of FMD in diabetes compared the vascular responses of 80 young IDDM patients with those of 80 matched non-diabetic controls,45Clarkson P Celermajer DS Donald AE et al.Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels.J Am Coll Cardiol. 1996; 28: 573-579Summary Full Text PDF PubMed Google Scholar and showed both reduced FMD and glyceryl trinitrate responses in the diabetic patients. The impairment of FMD was out of proportion to the impairment of the nitrate-mediated dilatation, which suggests that both the endothelial and smooth-muscle responses were abnormal. In this study, FMD was inversely related to both the duration of diabetes and the concentration of low-density-lipoprotein cholesterol.45Clarkson P Celermajer DS Donald AE et al.Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels.J Am Coll Cardiol. 1996; 28: 573-579Summary Full Text PDF PubMed Google Scholar In older NIDDM patients, FMD has been reported as substantially impaired compared with non-diabetic controls, whereas only a minor attenuation was found in the response to glyceryl trinitrate.46Goodfel

Since the Diabetes Control and Complications Trial demonstrated the substantial benefits of tight glycaemic control there has been renewed interest in the application of information technology (IT) based techniques for improving the day-to-day care of patients with diabetes mellitus. Computer-based educational approaches have a great deal of potential for patients use, and may offer a means of training more health-care professionals to deliver such improved care. In this article the potential role of IT in diabetes education is reviewed, focusing in particular on the application of compartmental models in both computer-based interactive simulators and educational video games. Close attention is devoted to practical applications-available today-for use by patients, their relatives, students and health-care professionals. The novel features and potential benefits of such methodologies are highlighted and some of the limitations of currently available software are discussed. The need for improved graphical user interfaces, and for further efforts to evaluate such programs and demonstrate an educational benefit from their use are identified as hurdles to their more widespread application. The review concludes with a look to the future and the type of modelling features which should be provided in the next generation of interactive diabetes simulators and educational video games.

OBJECTIVE While the effects of age on the growth hormone/insulin‐like growth factor (IGF) axis are well documented, the influence of ethnic background is unknown. The differences in IGF and IGF binding proteins (IGFBPs) were investigated in two ethnic groups. DESIGN A cross‐sectional study of an age‐selected cohort of healthy, normoglycaemic, non‐obese Caucasian (C) and Asian (A) subjects. PATIENTS Fifty‐three (27 C, 26 A) subjects with a mean age (±SD) of 20.6±0.8 years were studied. MEASUREMENTS Fasting measurements of glucose, insulin, IGF‐I, IGF‐II, IGFBP‐1 and IGFBP‐3. Western ligand blotting and immunoblotting with IGFBP‐2 and IGFBP‐3 of serum samples. RESULTS There were no significant differences in IGF‐I levels between Caucasian and Asian subjects (C 218±55 vs A 229±40μg/l; P=0.44). IGF‐II (C 707±110 vs A 583±75μg/l; P<0.0001) and IGFBP‐3 (C 5.9±1.2 vs A 5.12±1.17 mg/l; P=0.01) levels were significantly higher in Caucasian subjects. Immunoblotting of ligand blots revealed no protease activity on either IGFBP‐3 or IGFBP‐2 to account for these ethnic differences. CONCLUSIONS Ethnic differences in IGFBP‐3 and associated IGF‐II levels may affect the inter‐relationships of IGFs and their binding proteins and need to be considered when interpreting IGF data on growth and metabolism.

Conference Abstract| February 01 1996 Short Term Administration of Antioxidant Vitamins Decreases Aortic Distensibility in Patients with Established Atherosclerosis KD Hopkins; KD Hopkins 1Academic Department of Medicine, Whittington Hospital, Highgate Hill, London Search for other works by this author on: This Site PubMed Google Scholar SW Coppack; SW Coppack 1Academic Department of Medicine, Whittington Hospital, Highgate Hill, London Search for other works by this author on: This Site PubMed Google Scholar ED Lehmann; ED Lehmann 1Academic Department of Medicine, Whittington Hospital, Highgate Hill, London Search for other works by this author on: This Site PubMed Google Scholar A Rawesh; A Rawesh 1Academic Department of Medicine, Whittington Hospital, Highgate Hill, London Search for other works by this author on: This Site PubMed Google Scholar K Kongola; K Kongola *School of Applied Sciences, University of the South Bank, London, UK Search for other works by this author on: This Site PubMed Google Scholar RC Turay; RC Turay *School of Applied Sciences, University of the South Bank, London, UK Search for other works by this author on: This Site PubMed Google Scholar RG Gosling RG Gosling *School of Applied Sciences, University of the South Bank, London, UK Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1996) 90 (s34): 29P. https://doi.org/10.1042/cs090029Pb Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation KD Hopkins, SW Coppack, ED Lehmann, A Rawesh, K Kongola, RC Turay, RG Gosling; Short Term Administration of Antioxidant Vitamins Decreases Aortic Distensibility in Patients with Established Atherosclerosis. Clin Sci (Lond) 1 February 1996; 90 (s34): 29P. doi: https://doi.org/10.1042/cs090029Pb Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu nav search search input Search input auto suggest search filter All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1996 The Biochemical Society and the Medical Research Society1996 Article PDF first page preview Close Modal You do not currently have access to this content.

Conference Abstract| February 01 1996 Aortic Compliance in Patients with Stroke ED Lehmann; ED Lehmann 1Department of Imaging, National Heart and Lung Institute, Royal Brompton Hospital, London SW3 6NP2Stroke Unit, St. Thomas' Hospital, London; and School of Applied Sciences, University of the South Bank, London, UK Search for other works by this author on: This Site PubMed Google Scholar KD Hopkins; KD Hopkins 1Department of Imaging, National Heart and Lung Institute, Royal Brompton Hospital, London SW3 6NP2Stroke Unit, St. Thomas' Hospital, London; and School of Applied Sciences, University of the South Bank, London, UK Search for other works by this author on: This Site PubMed Google Scholar RL Jones; RL Jones 1Department of Imaging, National Heart and Lung Institute, Royal Brompton Hospital, London SW3 6NP2Stroke Unit, St. Thomas' Hospital, London; and School of Applied Sciences, University of the South Bank, London, UK Search for other works by this author on: This Site PubMed Google Scholar AG Rudd; AG Rudd 1Department of Imaging, National Heart and Lung Institute, Royal Brompton Hospital, London SW3 6NP2Stroke Unit, St. Thomas' Hospital, London; and School of Applied Sciences, University of the South Bank, London, UK Search for other works by this author on: This Site PubMed Google Scholar RG Gosling RG Gosling 1Department of Imaging, National Heart and Lung Institute, Royal Brompton Hospital, London SW3 6NP2Stroke Unit, St. Thomas' Hospital, London; and School of Applied Sciences, University of the South Bank, London, UK Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1996) 90 (s34): 29P. https://doi.org/10.1042/cs090029Pa Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation ED Lehmann, KD Hopkins, RL Jones, AG Rudd, RG Gosling; Aortic Compliance in Patients with Stroke. Clin Sci (Lond) 1 February 1996; 90 (s34): 29P. doi: https://doi.org/10.1042/cs090029Pa Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1996 The Biochemical Society and the Medical Research Society1996 Article PDF first page preview Close Modal You do not currently have access to this content.

Correspondence| February 01 1996 Definitions of Cardiac/Ventricular and Vascular/Arterial Compliance are Different E. D. Lehmann; E. D. Lehmann †Department of Imaging, National Heart and Lung Institute, Royal Brompton Hospital, London, U.K. Search for other works by this author on: This Site PubMed Google Scholar K. D. Hopkins; K. D. Hopkins ‡Academic Department of Medicine, Whittington Hospital, London, U.K. Search for other works by this author on: This Site PubMed Google Scholar R. G. Gosling R. G. Gosling §School of Applied Sciences, University of the South Bank, London, U.K. Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1996) 90 (2): 143–144. https://doi.org/10.1042/cs0900143 Article history Received: September 28 1995 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation E. D. Lehmann, K. D. Hopkins, R. G. Gosling; Definitions of Cardiac/Ventricular and Vascular/Arterial Compliance are Different. Clin Sci (Lond) 1 February 1996; 90 (2): 143–144. doi: https://doi.org/10.1042/cs0900143 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1996 The Biochemical Society and the Medical Research Society1996 Article PDF first page preview Close Modal You do not currently have access to this content.

Correspondence| May 01 1996 Multiple Definitions of ‘Compliance’ E. D. Lehmann; E. D. Lehmann *Department of Imaging, National Heart and Lung Institute, Royal Brompton Hospital, London, U.K. Search for other works by this author on: This Site PubMed Google Scholar K. D. Hopkins; K. D. Hopkins †Academic Department of Medicine, Whittington Hospital, London, U.K. Search for other works by this author on: This Site PubMed Google Scholar R. G. Gosling R. G. Gosling ‡School of Applied Sciences, University of the South Bank, London, U.K. Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1996) 90 (5): 433–434. https://doi.org/10.1042/cs0900433 Article history Received: February 13 1996 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation E. D. Lehmann, K. D. Hopkins, R. G. Gosling; Multiple Definitions of ‘Compliance’. Clin Sci (Lond) 1 May 1996; 90 (5): 433–434. doi: https://doi.org/10.1042/cs0900433 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1996 The Biochemical Society and the Medical Research Society1996 Article PDF first page preview Close Modal You do not currently have access to this content.