bluuebunny/crossref_metadata_2025 huggingface dataset:
Nocturnal enuresis in the adolescent: a neglected problem
Authors: Nappo S. , Del Gado R. , Chiozza M.L. , Biraghi M. , Ferrara P. , Caione P.
Published: March 2003

Objective To assess the features of adolescent bedwetters, as few data are available on enuresis in this age group.

Patients and methods A specific database for adolescents and young adults was created with the collaboration of various specialists (paediatricians, urologists, gynaecologists, psychiatrists). Questions focused on family and personal history, stressful events, age of attaining urinary and fecal control, characteristics of enuresis (primary vs secondary, monosymptomatic vs enuresis associated with daytime urinary symptoms), school performance, diagnostic examination and physical examinations, and treatment and its response.

Results Data were collected from 107 enuretic adolescents (mean age 15.3 years, median 14, range 13–23; 63 males and 44 females). A positive family history for enuresis was recorded in 82%. Enuresis was primary in 79 patients (74%), secondary in 28 (26%), monosymptomatic in 76 (71%) and associated with daytime urinary symptoms in 31 (29%). In males monosymptomatic enuresis was significantly more frequent than in females (P < 0.01). Urinary tract infections were reported by 13 patients, all females; eating disorders (anorexia, polyphagia) were present in six. In 85 patients (80%) enuresis was considered severe (≥ three nights/week). Of the 107 patients, 27 (20%) had never consulted a doctor about their problem and 43 (40%) had received no therapy; 66 received desmopressin monotherapy, with a good response (half the number of wet nights) in 44 (79%). There was no relation between response to desmopressin and gender, age, type and severity of enuresis or positive family history of enuresis. Eight patients were provided with a nocturnal alarm but this was not tolerated by two. Altogether, 25 patients refused any therapy or did not comply with the given therapy.

Conclusions Enuresis can persist into adolescence and be a significant problem; 80% of these patients had severe enuresis and 31% also had associated daytime urinary symptoms, with 40% receiving no previous therapy. The treatment of enuresis can be particularly difficult at this age; 22% of patients did not respond to desmopressin and 23% had low compliance with the given therapy. Enuresis in adolescents requires further study; hopefully more enuretic children will receive adequate treatment before reaching adolescence.
Spermatogenesis and spectral echo‐colour Doppler traces from the main testicular artery
Authors: Biagiotti G. , Cavallini G. , Modenini F. , Vitali G. , Gianaroli L.
Published: March 2003

Objective  To assess whether the peak systolic velocity (PSV), end‐diastolic velocity (EDV) and resistive index (RI) of testicular arteries may be useful in distinguishing the various causes of dyspermia when compared with follicle‐stimulating hormone (FSH) and testicular volume.

Patients, subjects and methods  The study included nine men with obstructive and 20 with unobstruc‐tive azoospermia, 17 with oligoasthenospermia and clinical varicoceles, with male accessory glans inflammation (MAGI), 38 with undetermined oligoasthenospermia, 19 with MAGI, 11 with clinical varicoceles, 32 subjects with normal sperm analysis and recent paternity (fertile controls), and 15 with normal sperm analysis and a varicocele with recent paternity (fertile + varicoceles). Testicular volume, FSH, PSV, EDV and RI were compared among the dyspermic and/or control groups using analysis of variance.

Results  The PSV and RI were useful for identifying the different groups of patients, while EDV, FSH and testicular volume were not. Men with varicoceles, varicoceles + MAGI or fertile with varicoceles had the highest PSV and RI; fertile controls, those with obstructive azoospermia and MAGI had similar PSVs and RIs, those with unexplained oligoasthenospermia had a significantly lower PSV and RI, and men with unobstructive azoospermia had the lowest PSV and RI.

Conclusions  The RI and PSV are reliable indicators for routine clinical use to identify infertile/dyspermic men, while EDV, FSH and testicular volume are not. The RI and especially PSV clearly differentiated obstructive from unobstructive azoospermia.
Validation of a flexible cystoscopy course
Authors: Shah J. , Montgomery B. , Langley S. , Darzi A.
Published: March 2003

Objective  To examine the instructional effectiveness of a course for nurses wishing to learn flexible cystoscopy, using a virtual reality flexible cystoscopy simulator to measure the outcome.

Subjects and methods  Fourteen urology nurse practitioners with no previous experience of cystoscopy were taught the basic techniques of flexible cystoscopy. They then had supervised group instruction during which they practised flexible cystoscopy on an inanimate latex model, and were taught how to handle the cystoscope, followed by unsupervised practice, including use of the virtual reality (VR) simulator (URO Mentor, Simbionix, Israel). They then undertook a cystoscopy task on the simulator; within the bladder there were 10 flags (numbered 1–10) at key positions. By visualizing and photographing each of the flags the subject would have visualized the entire bladder mucosa. The number of flags seen was thus used as a measure of how much of the bladder mucosa was examined. The VR simulator also measured the total procedure time. After a day of training the subjects were reassessed and the changes in performance evaluated. Subjects were also asked their opinion of the use of VR for flexible cystoscopy.

Results  The median (range) time to complete the procedure before the course was 3.33 (2–5.5) min and the number of flags seen 7 (6–9). After the course, the median time decreased to 2.85 (1.5–4.42) min and the number of flags seen increased to 8 (6–9). The change in time was significant (P = 0.03) but the difference in the number of flags was not (P = 0.12). All 14 subjects enjoyed the use of VR for learning flexible cystoscopy; they all reported that they were more confident in handling a flexible cystoscope and in undertaking flexible cystoscopy.

Conclusion  The virtual reality simulator was an effecctive tool for teaching flexible cystoscopy.
Current approaches to assessing the quality of life in children and adolescents
Authors: Gerharz E.W. , Eiser C. , Woodhouse C.R.J.
Published: March 2003

Urologists are well aware of the importance of the quality of life (QoL) in determining the success of their treatments. The public are increasingly aware of this aspect of medicine. The advent of fetal ultrasonography has made knowledge of QoL in long‐term survivors of congenital anomalies essential in counselling about pregnancy termination. It is becoming mandatory that clinical trials involving adults include an assessment of QoL. For children, measuring QoL has been restricted to life‐threatening conditions such as cancer or transplantation medicine. Measuring QoL is difficult in children and adolescents, and this is reflected in the few suitable instruments available. The development of sexuality contributes a further difficulty as many anxieties typical of those with genital anomalies may be common to all teenagers. Several instruments rely on the opinions of a proxy (parent or carer) but self‐assessment by the child is preferable where possible. The need for child self‐assessment is supported by finding little concordance between child and proxy assessments. While measuring QoL is challenging, we provide a substantial case for greater consideration of QoL in paediatric urology.
Quality control in urodynamics: a review of urodynamic traces from one centre
Authors: Sullivan J. , Lewis P. , Howell S. , Williams T. , Shepherd A.M. , Abrams P.
Published: March 2003

OBJECTIVE

To investigate quality control in our unit and to enable other units to compare their results, as experience from central reviews of urodynamic traces for multicentre trials has suggested that poor quality control is common.

PATIENTS AND METHODS

All consecutive male urodynamic tests conducted over 1 year were reviewed. A list of criteria to assess the quality of the records was devised, based upon International Continence Society guidelines on ‘good urodynamic practice’, and on other sources. Eligible traces were analysed for aspects of quality control, e.g. baseline pressures and coughs to test pressure transmission. The data were analysed to establish how often quality criteria were met, and identify areas for improvement.

RESULTS

In 100 eligible traces, the baseline detrusor pressure was 0–10 cmH2O in 86, and − 5 to +10 cmH2O in 94%. Baseline intravesical and abdominal pressure were 30–50 cmH2O in 68% and 73% of cases, respectively. Coughs were present before filling in 94%, during filling in 95%, before voiding in 72% and after voiding in 87% of cases. The cough‐test frequency was sufficient in 30% of traces. In 11 the intravesical pressure line fell out during voiding.

CONCLUSION

Most of the traces assessed met the quality criteria defined, but significant defects were not uncommon. Some of the problems identified suggest areas of urodynamic technique which should be studied in more detail. We intend to modify our quality control practices, and hope to show an improvement on re‐audit. We hope that other urodynamic departments will be encouraged to review their practice, and we aim to improve our results.
Pharmacological management of erectile dysfunction
Authors: Montorsi F. , Salonia A. , Deho' F. , Cestari A. , Guazzoni G. , Rigatti P. , Stief C.
Published: March 2003

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Many drugs are now available for treating ED; oral pharmacotherapy represents the first‐line option for most patients with ED. Sildenafil, an inhibitor of the enzyme phosphodiesterase type 5, is currently the most widely prescribed oral agent and has a very satisfactory efficacy‐safety profile in all patient categories. Apomorphine SL is a dopamine D1‐ and D2‐receptor agonist which has recently been approved for marketing in Europe. It is best selected for treating patients with mild to moderate ED. Vardenafil and tadalafil are new phosphodiesterase type 5 inhibitors which are expected to be approved this year. Both of them have significant positive efficacy‐safety profiles. Patients who do not respond to oral pharmacotherapy or who cannot use it are good candidates for intracavernosal and intraurethral therapy. Alprostadil is the most widely used drug, both for injection therapy and for the intraurethral route. The efficacy of second‐line treatment is high but the attrition rate remains significant.
Blood pressure control, microalbuminuria and cardiovascular risk in Type 2 diabetes mellitus
Authors: Marshall S. M.
Published: March 2003

Type 2 (noninsulin‐dependent) diabetes mellitus (DM) affects about 3% of the UK population. Diabetes often coexists with a cluster of other potent cardiovascular risk factors, including hypertension, dyslipidaemia and increased tendency for thrombosis, and increases the risk of early death from cardiovascular causes by about threefold. Microalbuminuria or proteinuria also may be present, further increasing the risk of cardiovascular mortality. Cardiovascular risk factors must be treated aggressively in patients with Type 2 diabetes and control of blood pressure at 140/85 mmHg or lower is a priority. The management of hypertension in patients from some ethnic groups demands special consideration because they have a high incidence of diabetes and hypertensive complications. Patients must be urged to adopt appropriate lifestyle changes in the first instance but additional drug treatment for hypertension is usually required. All the major classes of antihypertensive agents lower blood pressure in Type 2 diabetic patients but have different effects on metabolic risk factors in different ways. Low‐dose thiazide diuretics, β‐blockers, calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk. Individually, the effects of low‐dose thiazide diuretics and β‐blockers on glucose and lipid metabolism is clinically insignificant, though in combination much larger metabolic effects are seen. ACE inhibitors and calcium channel blockers have no, or small, beneficial effects on glucose and lipid metabolism, while the greater beneficial effects of α1‐blockers on lipid profiles may render them especially useful in the Type 2 diabetic patient. Long‐acting calcium‐channel blockers and ACE inhibitors protect renal function and are suitable as first line therapy in patients with microalbuminuria or proteinuria. Until results from the current batch of randomized, placebo‐controlled trials comparing different classes of antihypertensive agents are available, the choice of antihypertensive agent is difficult. Addressing overall cardiovascular risk factors, rather than hypertension alone, is essential in the management of the hypertensive Type 2 diabetic patient.

Diabet. Med. 16, 358–372 (1999)
Hypothalamic arousal, insulin resistance and Type 2 diabetes mellitus
Authors: Björntorp P. , Holm G. , Rosmond R.
Published: March 2003

Aims Type 2 diabetes mellitus (DM) develops when insulin resistance overcomes the capacity of compensatory insulin secretion. Insulin resistance may be induced via psychoneuroendocrine pathways, a possibility which has received little previous attention.

Methods We have used salivary cortisol measurements to monitor the activity of the hypothalamic–pituitary–adrenal (HPA) axis, the major controller of hormones involved in the regulation of peripheral insulin sensitivity under everyday conditions. The influence of external challenges, as well as the sensitivity of feedback regulation, were followed in randomly selected middle‐aged population samples.

Results In health there is a rhythmicity of cortisol secretion, with a high plasticity and efficient feedback control. In contrast, a group of subjects were identified with a flat, rigid day curve and poor feedback control, who showed consistent abnormalities in stress‐related cortisol secretion, including inhibited secretions of sex steroids and growth hormone; insulin resistance; abdominal obesity; elevated leptin levels; hyperglycaemia; dyslipidaemia and hypertension with elevated heart rate. The endocrine abnormalities are probably responsible for the anthropometric and metabolic abnormalities. The circulatory perturbations seem to be induced by a parallel activation of the central sympathetic nervous system suggesting an ‘hypothalamic arousal syndrome’, gradually developing into an independent risk for disease. An associated cluster of environmental factors, including psychosocial and socio‐economic stress, traits of depression and anxiety, alcohol consumption and smoking, all factors known to activate hypothalamic centres, has been identified. A polymorphism of the glucocorticoid receptor gene, with 13.7% homozygotes in the male Swedish population, parallels receptor dysfunction, and may be responsible for the associated insulin resistance, central obesity and hypertension.

Conclusions This is the first detailed examination of psychoneuroendocrinological processes in the natural environment on a population basis in relation to somatic health. The results suggest that an hypothalamic arousal syndrome, with parallel activation of the HPA axis and the central sympathetic nervous system, is responsible for development of endocrine abnormalities, insulin resistance, central obesity, dyslipidaemia and hypertension, leading to frank disease, including Type 2 DM. We suggest that this syndrome is probably based on environmental pressures in genetically susceptible individuals.

Diabet. Med. 16, 373–383 (1999)
Diabetes and driving: towards equitable, evidence‐based decision‐making
Authors: MacLeod K. M.
Published: March 2003

In January 1998, the British government introduced new restrictions on licensing of people with insulin‐treated diabetes mellitus to drive. These restrictions were based on the second EU driver licensing directive (91/4389) and looked to be costing insulin‐treated diabetic individuals their entitlement to drive light goods and small passenger‐carrying vehicles. In response to concerns expressed by the diabetes community in Britain, the British Diabetic Association commissioned a report examining and interpreting the available evidence of accident risk in insulin‐treated diabetic patients, particularly that related to unexpected hypoglycaemia. The following article is drawn from that report.
The British Diabetic Association Cohort Study, I: all‐cause mortality in patients with insulin‐treated diabetes mellitus
Authors: Laing S. P. , Swerdlow A. J. , Slater S. D. , Botha J. L. , Burden A. C. , Waugh N. R. , Smith A. W. M. , Hill R. D. , Bingley P. J. , Patterson C. C. , Qiao Z. , Keen H.
Published: March 2003

Aims To assess mortality in patients with diabetes incident under the age of 30 years.

Methods A cohort of 23 752 diabetic patients diagnosed under the age of 30 years from throughout the United Kingdom was identified during 1972–93 and followed up to February 1997. Following notification of deaths during this period, age‐ and sex‐specific mortality rates, attributable risks and standardized mortality rates were calculated.

Results The 23 752 patients contributed a total of 317 522 person‐years of follow‐up, an average of 13.4 years per subject. During follow‐up 949 deaths occurred in patients between the ages of 1 and 84 years, 566 in males and 383 in females. All‐cause mortality rates in the patients with diabetes exceeded those in the general population at all ages and within the cohort were higher for males than females at all ages except between 5 and 15 years. The relative risk of death (standardized mortality ratio, SMR), was higher for females than males at all ages, being 4.0 (95% CI 3.6–4.4) for females and 2.7 (2.5–2.9) for males overall, but reaching a peak of 5.7 (4.7–7.0) in females aged 20–29, and of 4.0 (3.1–5.0) in males aged 40–49. Attributable risks, or the excess deaths in persons with diabetes compared with the general population, increased with age in both sexes.

Conclusions This is the first study from the UK of young patients diagnosed with diabetes that is large enough to calculate detailed age‐specific mortality rates. This study provides a baseline for further studies of mortality and change in mortality within the United Kingdom.
Elevated plasma semicarbazide‐sensitive amine oxidase (SSAO) activity in Type 2 diabetes mellitus complicated by retinopathy
Authors: Garpenstrand H. , Ekblom J. , Bäcklund L. B. , Oreland L. , Rosenqvist U.
Published: March 2003

Aims To measure plasma semicarbazide‐sensitive amine oxidase (SSAO) activities and detect retinopathy in Type 2 diabetes mellitus (DM).

Methods Cross‐sectional, population‐based study of 65 diabetes patients (61 diagnosed from the age of 30 years) with or without retinopathy as determined by fundus photography in primary care. HbA1c was analysed by ion exchange chromatography on a Mono S for HbA1c column. SSAO activities were assayed radiometrically and formaldehyde‐albumin adducts by ELISA in plasma samples from patients and 136 healthy controls.

Results Subjects with diabetes had higher plasma SSAO activity, measured as nmol benzylamine.ml plasma‐1.h‐1(mean 20.6), than controls (mean 14.3), P < 0.0001; 95% confidence interval (CI) for difference 4.9–7.7. SSAO activity was higher in patients with retinopathy (mean 23.2) than in those without (mean 18.9), P = 0.012; 95% CI for difference 1.0–7.5, and related to the HbA1c value. No statistically significant relationship between diabetes duration and SSAO activity was found. With HbA1c values and insulin treatment entered into a multiple logistic regression model, SSAO activity no longer predicted retinopathy, P increasing from 0.025 to 0.17. SSAO activity and the presence of any retinopathy were unrelated to titres of antibodies against formaldehyde‐treated human serum albumin.

Conclusions SSAO activity, earlier found to be elevated in Type 1 DM, is also elevated in Type 2 DM. The SSAO family of enzymes may be involved in the development of diabetic retinopathy, possibly by catalysing the formation of toxic metabolites. A potent and specific inhibitor of human SSAO might help prevent retinopathy in Type 1 and Type 2 DM.
Relative hypoleptinaemia in women with mild gestational diabetes mellitus
Authors: Festa A. , Shnawa N. , Krugluger W. , Hopmeier P. , Schernthaner G. , Haffner S. M.
Published: March 2003

Aims There is increasing evidence suggesting that leptin plays a major role in the regulation of energy homeostasis, as well as in the neuroendocrine and reproductive systems. Leptin is synthesized in the human placenta. The aim of this study was to relate serum leptin levels during pregnancy to glucose tolerance, body mass index (BMI) and specific metabolic variables, such as specific insulin and proinsulin.

Methods A 2‐h 75 g oral glucose tolerance test was performed in 221 pregnant women at 22–29 weeks of gestation (median 25th week). Serum leptin was measured using a radioimmunoassay. In 49 women, sequential leptin measurements were performed (during pregnancy and post partum (median 5 months)).

Results During pregnancy serum leptin was significantly related to body weight (r = 0.49), BMI (r = 0.51), fasting immunoreactive insulin (r = 0.46), specific insulin (r = 0.43) and proinsulin (r = 0.29) (all P‐values < 0.0001). In women with mild gestational diabetes (GDM, n = 55), leptin levels were lower compared to women with normal glucose tolerance (n = 166) after adjusting for BMI and fasting insulin (26.9 vs. 19.4 ng/ml, P = 0.0001). Leptin was significantly higher during pregnancy compared to post partum (mean ± se: 24.3 ± 1.5 vs. 19.6 ± 1.6 ng/ml, P = 0.0003), even after adjustment for changes in BMI and changes in fasting insulin (P = 0.013).

Conclusions Leptin levels are elevated in pregnancy. Women with mild GDM presented with relative hypoleptinaemia compared to women with normal glucose tolerance.
Increased sympathetic activity during sleep and nocturnal hypertension in Type 2 diabetic patients with diabetic nephropathy
Authors: Nielsen F. S. , Hansen H. P. , Jacobsen P. , Rossing P. , Smidt U. M. , Christensen N. J. , Pevet P. , Vivien‐Roels B. , Parving H. ‐H.
Published: March 2003

Aims To elucidate the putative factors involved in the blunted nocturnal blood pressure reduction in hypertensive Type 2 diabetic patients with diabetic nephropathy.

Methods Extracellular fluid volume and fluid shift from interstitial to plasma volume (haematocrit), sympathetic nervous activity (plasma noradrenaline and adrenaline) and the internal ‘body clock’ (serum melatonin) were investigated in 31 hypertensive Type 2 diabetes mellitus (DM) patients with diabetic nephropathy (24 males, age 60 (45–73) years). All variables, except extracellular volume, were measured repeatedly with the patients lying awake in bed from 21:30 to 23:00 h (baseline) and during sleep from 23:00 to 07:00 h. Using the median nocturnal blood pressure reduction (8.4%) as a guide, the patients were divided into groups; group 1 with the highest and group 2 with the lowest nocturnal blood pressure reduction.

Results Haematocrit decreased from baseline to the sleep period in group 1 by a mean (95% confidence interval (CI)) of 1.7 (0.3–3.1)%, but it increased by 0.5 (–1.0–1.9)% in group 2, mean difference (95% CI), –2.1 (–4.0 to –0.2)% (P = 0.029). Noradrenaline decreased from baseline to the sleep period, mean (95% CI), by 13.3 (0.0–25.0)% in group 1 but rose by 7.7 (–9.7–28.4)% in group 2, mean difference (95% CI), –19.6 (–35–0.0)% (P = 0.049). The nocturnal blood pressure change correlated to the nocturnal change in both noradrenaline (r = 0.51, P = 0.004) and haematocrit (r = 0.42, P = 0.018). Adrenaline remained constant in both groups. Extracellular fluid volume and plasma melatonin levels were comparable in the two groups.

Conclusion Sustained adrenergic activity during sleep is associated with blunted nocturnal blood pressure reduction in hypertensive Type 2 DM patients with diabetic nephropathy, probably mediated through a lack of peripheral vasodilatation whereas changes in extracellular fluid volume distribution and melatonin secretion have no impact.
Relative activity and referral patterns for diabetes and non‐diabetes in general practice
Authors: Morgan C. LL. , Currie C. J. , Hunt J. , Evans J. D. , Rogers C. , Stott N. C. H. , Peters J. R.
Published: March 2003

Aims To describe and compare general practice (GP) activity for patients with and without diabetes using a survey of general practices representing over 10% of the Welsh population.

Methods The Welsh GP Morbidity Database Project (GPMDP) collected data including demographic and lifestyle information and consultation data such as diagnosis, referral and surgical procedures. These data were analysed to establish the annual period prevalence of diabetes and compare the relative number of consultations and referrals.

Results A total of 4182 diabetic patients were recorded (prevalence 1.41%) and accounted for 77 371 (4.4%) consultations. Patients with diabetes were four‐times more likely to be referred to community services (relative risk (RR) 4.1, 95% CI 3.7–4.7), in particular district nursing (RR 3.8, 1.9–7.7), optician services (RR 8.9, 5.0–15.7), chiropody (RR 8.2 6.4–10.5) and dietician services (RR 21.2, 17.6–25.5). Patients with diabetes were also more likely to be followed‐up in general practice (RR 6.7, 6.2–7.2) both within 1 month (RR 6.7, 6.2–7.2) and 1 month to 1 year (RR 9.7, 8.9–10.7). Emergency admissions were also more likely for patients with diabetes (RR 6.8, 6.2–7.5) as were elective admissions to general medicine (RR 5.6, 4.6–6.7), surgery (RR 1.8, 1.5–2.0) and opthalmology (4.2, 3.4–5.2).

Conclusion The increased utilization of health services apparent in secondary care was confirmed in primary care. Further research is required to determine levels of community activity after initial referral.
Early social mixing and childhood Type 1 diabetes mellitus: a case–control study in Yorkshire, UK
Authors: McKinney P. A. , Okasha M. , Parslow R. C. , Law G. R. , Gurney K. A. , Williams R. , Bodansky H. J.
Published: March 2003

Aims Evidence from animal models shows an increased risk of Type 1 diabetes mellitus associated with the absence of early life exposure to pathogens. To test this ‘hygiene hypothesis’, patterns of social mixing and infections in the first year of life and the risk of developing autoimmune diabetes in childhood were examined.

Methods Personal interviews were conducted with the mothers of 220 children with Type 1 diabetes (0–15 years) and 433 age/sex matched controls from a population‐based case control study in Yorkshire, UK. Social mixing including attendance at daycare, and infections occurring under 1 year of age were measures of exposure. Adjusted odds ratios (OR) were derived using conditional logistic regression.

Results Frequency of attendance at daycare during the 1st year of life was inversely associated with childhood diabetes (OR 0.71, 95% confidence interval 0.51–1.00, P = 0.05), a finding not explained by mother's age, level of education or maternal diabetes. Increasing numbers of children in the daycare setting and numbers of sessions attended were significantly associated with increasing protection from diabetes. The strongest effect was observed in children with diabetes diagnosed aged 0–4 years.

Conclusions Social mixing through attendance at daycare in early infancy appears to confer protection against the development of childhood diabetes. This may be mediated through exposure to infectious agent(s) as a significant dose–response effect was evident with increasing numbers of child ‘contacts’. These findings suggest early infectious exposure may play a role in the development of immunoregulatory mechanisms which protect against diabetes and further work is warranted.
Radicals and oxidative stress in diabetes
Authors: West I. C.
Published: March 2003

Recent evidence is reviewed indicating increased oxidative damage in Type 1 and Type 2 diabetes mellitus as well as deficits in antioxidant defence enzymes and vitamins. Mechanisms are considered whereby hyperglycaemia can increase oxidative stress, and change the redox potential of glutathione and whereby reactive oxygen species can cause hyperglycaemia. It is argued that oxygen, antioxidant defences, and cellular redox status should now be regarded as central players in diabetes and the metabolic syndrome.
Effects of three months' diet after diagnosis of Type 2 diabetes on plasma lipids and lipoproteins (UKPDS 45)
Authors:   UK Prospective Diabetes Study (UKPDS) Group, Manley S. E. , Stratton I. M. , Cull C. A. , Frighi V. , Eeley E. A. , Matthews D. R. , Holman R. R. , Turner R. C. , Neil H. A. W.
Published: March 2003

SUMMARY

Aims  To assess the effect of diet on fasting plasma lipids and lipoproteins in patients with newly diagnosed Type 2 diabetes.

Methods  A total of 2906 patients each underwent 3 months' diet therapy before allocation to therapy in a randomized controlled clinical trial. Lipids and lipoproteins were measured at diagnosis and after 3 months' diet.

Results  The mean body weight at diagnosis was 83 kg. Weight decreased after diet by a mean of 4.5 kg; body mass index (BMI) decreased by 1.51 kg/m2; plasma glucose fell by 3 mmol/l from 11 mmol/l; and HbA1c by 2% from 9%. Triglyceride concentrations were reduced in men by −0.41 (95% confidence interval (CI) −0.47 to − 0.35) mmol/l from a geometric mean 1.8 (1 sd interval 1.0–3.0) mmol/l, and in women by −0.23 (−0.28 to −0.18) mmol/l from a similar level. Cholesterol decreased in men by −0.28 (−0.33 to −0.24) mmol/l from 5.5 (1.1) mmol/l, and in women by −0.09 (−0.14 to −0.04) mmol/l from 5.8 (1.2) mmol/l with corresponding changes in LDL cholesterol. HDL cholesterol increased in men by 0.02 (0.01 to 0.04) mmol/l and in women by 0.01 (0 to 0.02) mmol/l. Triglyceride concentration in the top tertile was reduced by 37% in men (> 2.1 mmol/l) and by 23% in women (> 2.2 mmol/l) with regression to mean accounting for 13% and 6%, respectively. Similarly cholesterol in the top tertile was reduced by 12% in men (> 5.8 mmol/l) and 7% in women (> 6.2 mmol/l) with 6% of the decrease in both men and women accounted for by regression to the mean.

Conclusions  Initial dietary therapy in patients with newly diagnosed Type 2 diabetes substantially reduced plasma triglyceride, marginally improved total cholesterol and subfractions, and resulted in a potentially less atherogenic profile, although this did not eliminate the excess cardiovascular risk in patients with Type 2 diabetes.
Automated detection of microaneurysms in digital red‐free photographs: a diabetic retinopathy screening tool
Authors: Hipwell J. H. , Strachan F. , Olson J. A. , McHardy K. C. , Sharp P. F. , Forrester J. V.
Published: March 2003

SUMMARY

Aims  To develop a technique to detect microaneurysms automatically in 50° digital red‐free fundus photographs and evaluate its performance as a tool for screening diabetic patients for retinopathy.

Methods  Candidate microaneurysms are extracted, after the image has been modified to remove variations in background intensity, by algorithms that enhance small round features. Each microaneurysm candidate is then classified according to its intensity and size by the application of a set of rules derived from a training set of 102 images.

Results  When 3783 individual images were analysed and the results compared with the opinion of a clinical research fellow examining the same images, the program achieved a sensitivity of 81% and a specificity of 93% for the detection of images containing microaneurysms. Nine hundred and twenty‐five sets of 4 images per patient were then analysed and the total number of microaneurysms detected compared with the overall patient retinopathy grade derived by the clinician examining the same images. In this context, intended to mimic a screening situation, the program achieved a sensitivity of 85% and a specificity of 76% for the detection of patients with (any) retinopathy (positive predictive value 0.71, negative predictive value 0.88).

Conclusions  An automated technique was developed to detect retinopathy in digital red‐free fundus images that can form part of a diabetic retinopathy screening programme. It is believed that it can perform a useful role in this context identifying images worthy of closer inspection or eliminating 50% or more of the screening population who have no retinopathy.
Evidence‐based patient information in diabetes
Authors: Mühlhauser I. , Berger M.
Published: March 2003

Patient education in diabetes has been successful in training and motivating patients to assume a more active and independent role in monitoring and treating their disease resulting in an improvement of patient‐orientated outcomes. Traditionally, diabetes education has mainly aimed at increasing patient compliance to physician‐defined therapeutic goals and treatment strategies. To strengthen their rights and autonomy, patients need to become more involved in medical decision making with respect to their individual therapeutic goals, such as HbA1c and blood pressure, body weight, etc., as well as choosing whether they pursue these goals. The importance of patient participatation is particularly relevant to Type 2 diabetes. Even perfect, long‐term therapeutic co‐operation will not eliminate diabetic complications, only reduce the risk of developing them. The benefits, lack of benefits and unwanted effects of various interventions need to be communicated to the patient in an unbiased manner, so that he/she can make an informed choice with regard to different therapeutic goals and strategies. In diabetes, ways of presenting patients with unbiased information to enable them to make such informed decisions are not yet available. We present ways of how this might be achieved using data provided by the UKPDS. The concept of patient participation in medical decision making represents a fundamental challenge for the future development of diabetes care.
No reactive hypoglycaemia in Type 2 diabetic patients after subcutaneous administration of GLP‐1 and intravenous glucose
Authors: Vilsbøll T. , Krarup T. , Madsbad S. , Holst J. J.
Published: March 2003

SUMMARY

Aims  It has previously been shown that intravenous and subcutaneous administration of glucagon‐like peptide (GLP)‐1 concomitant with intravenous glucose results in reactive hypoglycaemia in healthy subjects. Since GLP‐1 is also effective in Type 2 diabetic patients and is presently being evaluated as a therapeutic agent in this disease, it is important to investigate whether GLP‐1 can cause hypoglycaemia in such patients.

Methods  Eight Type 2 diabetic patients (age 54 (49–67) years; body mass index 31 (27–38) kg/m2; HbA1c 9.4 (7.0–12.5)%) and seven matched non‐diabetic subjects (HbA1c 5.5 (5.2–5.8)%, fasting plasma glucose 5.4 (5.0–5.7) mmol/l) were given a subcutaneous injection of 1.5 nmol GLP‐1/kg body weight (maximally tolerated dose), and 15 min later, plasma glucose (PG) was raised to 15 mmol/l with an intravenous glucose bolus.

Results  Hypoglycaemia with a PG at or below 2.5 mmol/l was seen in five of the seven healthy subjects after 60–70 min, but PG spontaneously increased again, reaching 3.7 (3.3–4.0) mmol/l at 90 min. In the patients, PG fell slowly and stabilized at 8.6 (4.2–12.1) mmol/l after 80 min. In both groups, glucagon levels initially decreased, but later increased, exceeding basal levels in healthy subjects, in spite of persistent, high concentrations of GLP‐1 (P < 0.02).

Conclusions  Subcutaneous GLP‐1 plus intravenous glucose induced reactive hypoglycaemia in healthy subjects, but not in Type 2 diabetic patients. Therefore, a GLP‐1‐based therapy would not be expected to be associated with an increased risk of hypoglycaemia in Type 2 diabetes mellitus.
Abnormal cardiovascular reflex tests are predictors of mortality in Type 2 diabetes mellitus
Authors: Chen H. S. , Hwu C. M. , Kuo B. I. , Chiang S. C. , Kwok C. F. , Lee S. H. , Lee Y. S. , Weih M. J. , Hsiao L. C. , Lin S. H. , Ho L. T.
Published: March 2003

SUMMARY

Aims  To determine whether diabetic autonomic neuropathy is an important factor contributing to mortality in Type 2 diabetes mellitus.

Methods  Between 1989 and 1993, 431 men and 181 women with Type 2 diabetes were given diabetic autonomic neuropathy cardiovascular reflex (CVR) tests. These subjects were followed for the subsequent 5–9 years to assess mortality rates.

Results  The prevalence rate of abnormal CVR tests was 46.1% in patients with the history of diabetes less than 5 years and up to 69.4% when the history of diabetes exceeded 20 years. During the follow‐up period from 1 January 1989 to 31 December 1997 (mean 7.7 years), a total of 135 participants died. The 8‐year survival rate for patients with abnormal CVR tests was 63.6% in males and 76.4% in females, compared with 80.9 and 93.3% for patients with normal CVR tests. The results were grouped as: group 1, normal CVR tests without postural hypotension (PHT); group 2, normal CVR tests with PHT; group 3, abnormal CVR tests without PHT; and group 4, abnormal CVR tests with PHT. The 8‐year survival rate was 85.4% in group 1, 80.9% in group 2, 74.5% in group 3 and 61.1% in group 4.

Conclusion  Type 2 diabetic patients with abnormal CVR tests may have increased mortality, and those combined with postural hypotension have higher mortality than those without. Abnormal CVR tests may be important predictors of mortality in Type 2 diabetes mellitus.
Effect of troglitazone on urinary albumin excretion and serum type IV collagen concentrations in Type 2 diabetic patients with microalbuminuria or macroalbuminuria
Authors: Nakamura T. , Ushiyama C. , Suzuki S. , Shimada N. , Sekizuka K. , Ebihara L. , Koide H.
Published: March 2003

Aims  Troglitazone, a newly developed thiazolidinedione derivative, has been shown to ameliorate microalbuminuria in diabetic animal model and in human diabetic nephropathy in short‐term studies. The aim of the present study was to determine whether troglitazone or sulphonylurea affect micro‐ albuminuria, macroalbuminuria, or serum type IV collagen concentrations in patients with diabetic nephropathy.

Methods  We studied 32 normotensive patients with type 2 diabetes mellitus associated with microalbuminuria (n = 16) or macroalbuminuria (n = 16) and 20 healthy controls. The patients were randomly assigned to one of two groups: those treated with glibenclamide (5.0 mg/day) (n = 8) and those treated with troglitazone (400 mg/day) (n = 8). They received the drug regimen for 12 months. Serum type IV collagen was measured with sandwich enzyme immunoassay.

Results  Type IV collagen concentrations in macroalbuminuric patients were higher than those in microalbuminuric patients (P < 0.05) and healthy controls (P < 0.01). Troglitazone reduced urinary albumin excretion (UAE) in micro‐ albuminuric patients from 126 μg/min (range 58–180 μg/min) to 42 μg/min (range 14–80 μg/min) (P < 0.01) and also reduced serum type IV collagen levels gradually at 3, 6 and 12 months after treatment (P < 0.05). However, glibenclamide did not affect UAE and type IV collagen levels in micro‐ albuminuric diabetes patients. In addition, neither troglitazone nor gliben‐ clamide changed UAE and type IV collagen levels in macroalbuminuric patients.

Conclusions  These data suggest that troglitazone is an effective treatment for renal injury in patients with early diabetic nephropathy.
Prediction of Type 2 diabetes in healthy middle‐aged men with special emphasis on glucose homeostasis. Results from 22.5 years' follow‐up
Authors: Bjørnholt J. V. , Erikssen G. , Liestøl K. , Jervell J. , Erikssen J. , Thaulow E.
Published: March 2003

SUMMARY

Aims  To study the glucose disappearance rate and fasting blood glucose as predictors of Type 2 diabetes in a 22.5‐year prospective follow‐up of 1947 healthy non‐diabetic men.

Subjects and methods  Of a cohort of 2014 Caucasian men, the 1947 who had both fasting blood glucose < 110 mg/dl and an intravenous glucose tolerance test were included. A number of other physiological parameters were also determined at baseline. Multivariate Cox regression analyses were used to investigate the possible significance of the glucose disappearance rate and fasting blood glucose as predictors of Type 2 diabetes.

Results  After 22.5 years' follow‐up, 143 cases of Type 2 diabetes had developed. Glucose disappearance rate and fasting blood glucose were moderately correlated (r = −0.32). Men in the lowest quartile of glucose disappearance rate and highest quartile of fasting blood glucose had markedly higher diabetes rates than all other men (P < 0.0001). After adjusting for each other, age, diabetes heredity, body mass index, physical fitness, triglycerides, cholesterol and blood pressure (Cox model), both glucose disappearance rate and fasting blood glucose remained major predictors of diabetes

Conclusions  Glucose disappearance rate and fasting blood glucose are, in spite of low intercorrelation, major long‐term predictors of Type 2 diabetes in healthy non‐diabetic Caucasian men.
Calcaneal ultrasonometry in patients with Charcot osteoarthropathy and its relationship with densitometry in the lumbar spine and femoral neck and with markers of bone turnover
Authors: Jirkovská A. , Kasalický P. , Bouček P. , Hosová J. , Skibová J.
Published: March 2003

Aims  To assess calcaneal ultrasonometry in Charcot osteoarthropathy (CO) and to compare it with densitometry measured by dual energy X‐ray absorptiometry (DEXA) and with bone remodelling markers.

Patients and methods  A group of 16 diabetic patients in the acute stage of CO with a mean age (± sd) of 51 ± 13 years was compared with 26 sex‐ and age‐matched control subjects. Both calcaneal quantitative ultrasound (QUS) parameter stiffness and bone mineral density (BMD) measured in lumbar spine and femoral neck by DEXA were compared. Collagen type I cross‐linked C‐telopeptides (ICTP) were used for assessment of bone resorption.

Results  Patients with acute CO had significantly lower stiffness of the calcaneus in the Charcot and non‐Charcot foot (both P < 0.001) and significantly lower femoral neck BMD (P < 0.05) in comparison with the control group. The T‐score of stiffness was significantly lower in the Charcot foot compared with the non‐Charcot foot (−3.00 ± 1.39 vs. −2.36 ± 1.12; P < 0.01) and significantly lower than the mean T‐score of BMD in the lumbar spine (−0.57 ± 1.28; P < 0.001) and femoral neck (−1.58 ± 1.24; P < 0.05). A significant difference in ICTP (8.49 ± 4.37 vs. 3.92 ± 2.55 ng/ml; P < 0.001) between patients with CO and the control group was found, and a significant correlation was demonstrated between ICTP and the T‐score of stiffness (r = −0.73; P < 0.01).

Conclusion  The lower calcaneal QUS parameter stiffness in the Charcot foot in comparison with the control group, with the non‐Charcot foot and with BMD in the lumbar spine and femoral neck, and its association with increased bone resorption indicate that calcaneal ultrasonometry may be useful in diagnosing the acute stage of CO and in assessing the risk of foot fracture.

Diabet. Med. 18, 495–500 (2001)
Association of lipoprotein(a) levels and apolipoprotein(a) phenotypes with coronary artery disease in Type 2 diabetic patients and in non‐diabetic subjects
Authors: Gazzaruso C. , Garzaniti A. , Falcone C. , Geroldi D. , Finardi G. , Fratino P.
Published: March 2003

Aims  We investigated whether in Type 2 diabetic patients lipoprotein(a) (Lp(a)) levels and apolipoprotein(a) (apo(a)) polymorphism are associated with angiographically documented coronary artery disease (CAD). We also examined whether there are differences in the distributions of Lp(a) levels and apo(a) phenotypes between CAD patients with and without diabetes.

Methods  A hundred and seven diabetic patients with CAD, 274 diabetic patients without CAD, 201 non‐diabetic patients with CAD, and 358 controls were enrolled.

Results  Diabetic patients with CAD showed Lp(a) levels (21.2 ± 17.7 vs. 15.1 ± 17.8 mg/dl; P = 0.0018) and a percentage of subjects with at least one apo(a) isoform of low molecular weight (MW) (67.2% vs. 27.7%; P = 0.0000) significantly greater than diabetic patients without CAD. Multivariate analysis showed that in diabetic patients Lp(a) levels and apo(a) phenotypes were significantly associated with CAD; odds ratios (ORs) of high Lp(a) levels for CAD were 2.17 (1.28–3.66), while ORs of the presence of at least one apo(a) isoform of low MW were 5.35 (3.30–8.60). Lp(a) levels (30.2 ± 23.7 vs. 21.2 ± 17.7 mg/dl; P = 0.0005) and the percentage of subjects with at least one apo(a) isoform of low MW (87.0% vs. 67.2%; P = 0.0001) were significantly higher in CAD patients without than in those with diabetes.

Conclusions  Our data suggest that Lp(a) levels and apo(a) phenotypes are independently associated with CAD in Type 2 diabetic patients; thus both these parameters may be helpful in selecting diabetic subjects at high genetic cardiovascular risk. However, Lp(a) levels and apo(a) polymorphism seem to be cardiovascular risk factors less important in diabetic than in non‐diabetic subjects.

Diabet. Med. 18, 589–594 (2001)
HOPE for patients with Type 2 diabetes: an application of the findings of the MICRO‐HOPE substudy in a British hospital diabetes clinic
Authors: Jones S. C. , Bowes P. D. , Hall E. , Connolly V. , Kelly W. F. , Bilous R. W.
Published: March 2003

Aims  The MICRO‐HOPE substudy demonstrated that when ramipril treatment was added to people with Type 2 diabetes and additional cardiovascular risk factors cardiovascular events were reduced by 25% in 4.5 years. We wished to determine the proportion of people with Type 2 diabetes and additional cardiovascular risk factors registered with a hospital diabetes service.

Methods  Non‐proteinuric people (n = 1370) with Type 2 diabetes identified on our diabetes register were subject to analysis. Anticipated reductions in cardiovascular events due to ramipril treatment were based on reductions observed in the MICRO‐HOPE substudy.

Results  Non‐proteinuric people (n = 1075 (78%)) with Type 2 diabetes had at least one additional cardiovascular risk factor. Twenty‐nine percent were already taking an angiotensin‐converting enzyme inhibitor. The remaining 764 patients were similar to ramipril‐treated participants in the MICRO‐HOPE substudy. Treatment with ramipril for 4.5 years would be anticipated to reduce cardiovascular deaths by 26, revascularization procedures by 19 and admissions for myocardial infarction and stroke by 18 and 26, respectively.

Conclusions  Of non‐proteinuric people with Type 2 diabetes, 78% have additional cardiovascular risk factors. Only a small proportion currently receive treatment with an angiotensin‐converting enzyme inhibitor. The incidence of cardiovascular events could be reduced if more patients were treated with ramipril and other cardiovascular risk factors were addressed.

Diabet. Med. 18, 667–670 (2001)