bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent trends in the use of radical prostatectomy in England: the epidemiology of diffusion
Authors: Oliver S.E. , Donovan J.L. , Peters T.J. , Frankel S. , Hamdy F.C. , Neal D.E.
Published: March 2003

OBJECTIVE

To describe recent trends in the use of radical prostatectomy (RP) in England, as there is currently no consensus on the most effective treatment for localized prostate cancer, although RP is the treatment of choice among urological surgeons for men aged < 70 years.

METHODS

Routine data were assessed to establish the number of RPs performed in England in 1991–99. Age‐standardized operation rates were compared by region and socio‐economic group, and the geographical spread of use mapped.

RESULTS

The number of RPs performed annually increased nearly 20‐fold between 1991 and 1999. Rates of surgery were greatest in the London National Health Service (NHS) regions and lowest in the Trent region. Outside London, the risk of surgery in a NHS hospital was significantly greater for men living in the least deprived areas; in London this trend was reversed.

CONCLUSION

Rapid increases in the use of RP showed marked regional variations, most likely related to access to prostate‐specific antigen testing and the location of surgeons able to carry out radical surgery. By 1999, a third of procedures were still being undertaken in ‘low‐volume’ hospitals, with implications for the quality of care and outcomes. Crucially, these developments occurred in the absence of robust information about the effectiveness of RP. Recent funding of a randomized trial of treatment options in this area is welcome, but wider questions remain about the timing of the evaluation of surgical technologies.
Endoluminal ultrasonography before retrograde endopyelotomy: can the results match laparoscopic pyeloplasty?
Authors: Parkin J. , Evans S. , Kumar P.V.S. , Timoney A.G. , Keeley F.X.
Published: March 2003

In this paper, the authors assess whether endoluminal ultrasonography is helpful when carried out before retrograde endopyelotomy, and ask whether it can help to produce results comparable to laparoscopic pyeloplasty. They found that endopyelotomy was not as good in the presence of crossing vessels, despite using endoluminal ultrasonography, and they propose that laparoscopic pyeloplasty should be used in this situation.

OBJECTIVE

To present the results of endopyelotomy using endoluminal ultrasonography (EUS) to identify crossing vessels, as the success rates of endopyelotomy are generally lower than pyeloplasty, especially in patients with crossing vessels.

PATIENTS AND METHODS

Forty‐one consecutive patients who underwent EUS before a planned retrograde endopyelotomy were analysed retrospectively. EUS was used to direct the endopyelotomy incision for patients with crossing vessels. Treatment was considered successful if the patient was asymptomatic and unobstructed or improved on renography. The results were compared to those from 18 patients treated by laparoscopic pyeloplasty, some of whom had undergone EUS.

RESULTS

Crossing vessels were identified in 27 of the 41 patients (66%). Primary treatment consisted of endopyelotomy for 26 patients and laparoscopic pyeloplasty for 15. The overall success rate for 24 endopyelotomy patients with an adequate follow‐up (mean 19 months) was 71%, with more success in patients with no crossing vessels (11 of 13 (85%) vs six of 11 (55%)). Of the 18 patients treated by laparoscopic pyeloplasty (mean follow‐up 15.1 months) 17 were successful.

CONCLUSION

The results for endopyelotomy were disappointing in patients with crossing vessels, despite using EUS. The results suggest that patients with crossing vessels should be treated by laparoscopic pyeloplasty. More data are needed to compare endopyelotomy with laparoscopic pyeloplasty in patients with no crossing vessels.
Maternity services for women with diabetes in the UK
Authors: Hawthorne G. , Modder J.
Published: March 2003

Diabetic pregnancy is high risk in those regions within the UK that have reported on such an outcome. There is a paucity of information about diabetic pregnancy outcome in the rest of the UK but it seems appropriate to assume that poor outcome is widespread. Previously reports have highlighted problems with the delivery of preconception care and the lack of agreement about the screening and diagnosis of gestational diabetes. The provision of maternity services for women with diabetes in the UK is reviewed. Service development is traced from the 1980s to more recent surveys from Scotland and the former Northern region of England. Service provision has improved over the years in those regions that have agreed and audited standards for provision of care. There is a lack of information about current services within the UK but this will be partly addressed by the forthcoming survey of organization of services co‐ordinated by the Confidential Enquiry into Stillbirths and deaths in Infancy (CESDI), which will survey England, Wales and Northern Ireland. In Scotland the Scottish Intercollegiate Guidelines ‘Management of diabetes in pregnancy’ has been implemented and audited. A similar guideline of agreed standards of care is needed for the rest of the UK.
The GP perspective: problems experienced in providing diabetes care in UK general practice
Authors: Agarwal G. , Pierce M. , Ridout D. ,   Primary Care Diabetes (the Primary Care Section of the British Diabetic Association)
Published: March 2003

Aims To describe the problems and barriers perceived by general practitioners (GPs) whilst providing diabetes care in primary care in England and Wales and to identify those health authorities (HAs) in which primary care reported the most and least difficulty.

Design Descriptive postal survey using a self‐administered questionnaire.

Subjects One thousand eight hundred and seventy‐three randomly sampled GP practices (one in five practices).

Results One thousand three hundred and twenty (70%) responded. Getting patients to alter their lifestyles was perceived as causing the most difficulty in managing individual patients, followed by lack of time, patients’ nonattendance, noncompliance with medical regimens and poor communication with secondary care. The greatest barriers to practices providing desirable care were lack of time/under‐funding and keeping up to date in the area of diabetes, followed by lack of space, inadequate chiropody, dietetics, ophthalmology and access to secondary care. There are important differences between HAs in the difficulties experienced by primary care teams and we have ranked the HAs accordingly.

Conclusion The study has identified what problems need tackling in order to assist primary care to deliver good quality diabetes care, and has highlighted HAs where primary care needs further help, and HAs where examples of good practice may be found and useful lessons learnt. This should form the basis of a needs‐based research and development programme for diabetes in primary care.
Type 2 diabetes mellitus, cognitive impairment and dementia
Authors: Stewart R. , Liolitsa D.
Published: March 2003

Aims We set out to examine the evidence for an association between cognitive impairment or dementia and the presence of Type 2 diabetes mellitus (DM). We also sought evidence of potential mechanisms for such an association.

Methods A literature search of three databases was performed and the reference lists of the papers so identified were examined, using English language papers only.

Results We found evidence of cross‐sectional and prospective associations between Type 2 DM and cognitive impairment, probably both for memory and executive function. There is also evidence for an elevated risk of both vascular dementia and Alzheimer’s disease in Type 2 DM albeit with strong interaction of other factors such as hypertension, dyslipidaemia and apolipoprotein E phenotype. Both vascular and non‐vascular factors are likely to play a role in dementia in diabetes.

Conclusions Current classification structures for dementia may not be adequate in diabetes, where mixed pathogenesis is likely. Further research into the mechanisms of cognitive impairment in Type 2 DM may allow us to challenge the concept of dementia, at least in these patients, as an irremediable disease.

Diabet. Med. 16, 93–112 (1999)
Effects of insulin administration in a group of high‐risk, non‐diabetic, first‐degree relatives of Type 1 diabetic patients: an open pilot trial
Authors: Rodríguez‐Villar C. , Conget I. , Casamitjana R. , Ercilla G. , Gomis R.
Published: March 2003

Aims To elucidate the effect of prophylactic insulin, in a treatment schedule previously demonstrated to achieve β‐cell rest, in a group of high‐risk, non‐diabetic first‐degree relatives of Type 1 diabetic patients.

Methods Ten high risk subjects for Type 1 diabetes mellitus (DM) (seven male/three female, aged 19.8 ± 9.6 years) defined as: first‐degree relatives of Type 1 DM patients, islet cell autoantibodies (ICA) ≥20 Juvenile Diabetes Foundation (JDF) units twice, first phase insulin response (FPIR) to glucose in an intravenous glucose tolerance test ≤10th percentile of a control group were included in an open pilot trial. Five were treated with subcutaneous insulin: 0.1 IU/kg body weight/day of neutral protamine hagedorn (NPH) insulin once a day. Five declined treatment and were used as controls. Control and treatment groups did not differ in terms of age, ICA, insulin autoantibodies (IAA), glutamic acid dehydrogenase (GAD) and FPIR.

Results Three out of five subjects in both groups developed Type 1 DM during follow‐up: after 21, and 32–57 months in the insulin‐treated group and after 4, and 18–60 months in the untreated group. Three out of six subjects who developed overt diabetes had a FPIR below the 2nd percentile of the control value at the onset of the study. All subjects who developed diabetes were positive for antibodies to GAD and expressed the HLA‐DR3 or DR4 alleles, whereas only one of the nono‐progessors had these parameters (P < 0.05). During follow‐up, a decrease in ICA titres was observed in the group which received prophylactic insulin in contrast with the untreated group. GAD, as well as insulin secretory capacity, remained unchanged in both groups.

Conclusion The subcutaneous administration of insulin (0.1 IU/kg body weight/day of NPH insulin once a day) in our group of high‐risk subjects for Type 1 DM produced only a minor effect in some immunological markers (ICA), without preventing the development of overt disease. The efficacy and safety of insulin used at either a different dose or by a different route, as well as its potential effect in the early phases of prediabetes, warrants further investigation.

Diabet. Med. 16, 160–163 (1999)
Effect of different times of administration of a single ethanol dose on insulin action, insulin secretion and redox state
Authors: Trojan N. , Pavan P. , Iori E. , Vettore M. , Marescotti M. C. , Macdonald I. A. , Tiengo A. , Pacini G. , Avogaro A.
Published: March 2003

Aims Ethanol (EtOH) can affect glucose metabolism by altering the redox state, insulin‐mediated glucose uptake and insulin secretion. We sought to determine the effects of an acute oral EtOH load on insulin secretion and glucose tolerance and the importance of a different timing of administration relative to a glucose load.

Methods Eleven subjects underwent a frequently sampled intravenous glucose tolerance test (FSIGT) on three occasions in random order. In one, EtOH was given 50 min ‘before’ the FSIGT; on the second, the same amount was administered 6 min after the glucose pulse (‘during’ study); on the third no EtOH was given.

Results Blood EtOH peaked at 4.43 ± 0.24 mmol/l (mean ± sd) in the ‘during’ and 4.16 ± 0.31 mmol/l in the ‘before’ study. No differences were noticed in SI, the index of insulin sensitivity, or in SG, the glucose effectiveness, between the ‘before’, ‘during’ and control studies. There were no differences in the first‐phase insulin secretion between the three studies but a significant increase in the sensitivity to glucose of second‐phase dynamic insulin response, Φ2, in the ‘before’ (0.062 ± 0.036 pmol.min–2.(mg–1.dl–1)–1) and ‘during’ (0.063 ± 0.059) studies, compared to the control study (0.017 ± 0.010, P < 0.05) was observed. No differences were observed in the hepatic extraction of insulin. In the ‘before’ study, there was a significant decline in NEFA (non‐esterified fatty acid) concentration from the baseline (mean 602 ± 51 μmol/l) to the 0 min value (mean 353 ± 37, P < 0.01). During the FSIGT, the mean plasma NEFA concentration was significantly lower in the ‘before’ and in the ‘during’ than in the control study.

Conclusion An acute oral EtOH load does not impair glucose metabolism, at least in part because of an increased second‐phase insulin secretion. Since this effect is observed irrespective of whether EtOH is consumed either before or during the glucose load, the existence of a priming effect is questioned.

Diabet. Med. 16, 400–407 (1999)
The effect of long‐term glycaemic control on serum lipoprotein(a) levels in patients with Type 2 diabetes mellitus
Authors: Song K. ‐H. , Ahn Y. ‐B. , Yoon K. ‐H. , Cha B. ‐Y. , Lee K. ‐W. , Son H. ‐Y. , Kang S. ‐K.
Published: March 2003

Aims To examine whether long‐term glycaemic control affects lipoprotein(a) (Lp(a)) levels in patients with Type 2 diabetes mellitus.

Methods Eighty‐nine Type 2 diabetic patients (38 men, 51 women) were recruited from the diabetes clinic. Based on HbA1c concentrations at baseline, patients were divided into two groups: those with HbA1c <  8.0% (n=  45) and those with HbA1c≥  8.0% (n=  44). Comparisons of Lp(a) levels were made between both groups. The effect of long‐term glycaemic control on Lp(a) levels was investigated in a subgroup of 20 patients, selected from those with baseline HbA1c≥  8%. All these patients were treated with a goal of HbA1c <  7%.

Results Lp(a) levels were not significantly different between those with HbA1c <  8.0% and those with HbA1c≥  8.0%. No correlation between Lp(a) and HbA1c or fasting blood glucose levels was noted in diabetic patients as a whole. After 2 years of intensive glycaemic control, all patients exhibited remarkable improvement of therapy: their average HbA1c levels were 6.5 ± 0.7%, being <  7% in 70% of patients. However, no change in Lp(a) levels were observed after 2 years (19.5 ± 14.8–21.4 ± 13.4 mg/dl, P=  0.390).

Conclusion These results indicate that improvement of glycaemic control does not affect serum Lp(a) levels in patients with Type 2 diabetes mellitus.
Childhood Type 1 diabetes mellitus and parental occupations involving social mixing and infectious contacts: two population‐based case–control studies
Authors: Fear N. T. , McKinney P. A. , Patterson C. C. , Parslow R. C. , Bodansky H. J.
Published: March 2003

Aims To test the hypothesis that increased exposure to infections, through parental jobs involving high levels of social mixing, reduces the risk of childhood Type 1 diabetes mellitus.

Methods Two population‐based case–control studies of children diagnosed with Type 1 diabetes mellitus from Yorkshire (0–15 years) and Northern Ireland (0–14 years) included 220 and 189 cases and 433 and 465 controls, respectively. Parental occupations were coded using a standard occupational classification. Each job was allocated to high, medium or low levels of social mixing according to a predefined categorization. Odds ratios (OR) for the risk of childhood Type 1 diabetes were estimated for parental social mixing by age at diagnosis.

Results Childhood Type 1 diabetes mellitus was not associated with high levels of parental occupational social mixing (Yorkshire – mothers: OR 1.07, 95% confidence interval (CI) 0.76–1.50; fathers: 1.15, 0.75–1.76; Northern Ireland – heads of household, usually the father: 0.78, 0.49–1.25). A larger proportion of mothers (39%) compared to fathers (18% Yorkshire, 17% Northern Ireland) had jobs involving high levels of social mixing. Mothers with high social mixing jobs conferred a nonsignificant reduced risk of Type 1 diabetes among children diagnosed under 5 years of age (0.58, 0.24–1.38) compared to those diagnosed at age 5 years and above (1.14, 0.77–1.69).

Conclusions No association between parental occupational social mixing and the risk of childhood Type 1 diabetes mellitus was detected for all ages combined. Mothers were more likely to have jobs involving high levels of social mixing than fathers. The possible protective effect of maternal high occupational social mixing on children diagnosed below 5 years of age merits further investigation.
Clinico‐pathological features of postural hypotension in diabetic autonomic neuropathy
Authors: Khawaja K. I. , Walker D. , Hayat S. A. , Boulton A. J. M. , Malik R. A.
Published: March 2003

We report the clinico‐pathological features and management of a 49‐year‐old male with a 30‐year history of Type 1 diabetes mellitus who had nephropathy (proteinuria 1.81 g/24 h, creatinine 136 μmol/l), proliferative retinopathy and severe somatic and autonomic neuropathy. A sural nerve biopsy demonstrated marked myelinated fibre loss with unmyelinated fibre degeneration and regeneration combined with extensive endoneurial microangiopathy. The management of the patient's blood pressure problems (supine hypertension) and symptomatic postural hypotension is discussed.
Interaction between the Asn291Ser variant of the LPL gene and insulin resistance on dyslipidaemia in high risk individuals for Type 2 diabetes mellitus
Authors: Klannemark M. , Suurinkeroinen L. , Orho‐Melander M. , Groop L. , Taskinen M. ‐R.
Published: March 2003

SUMMARY

Aims   Lipoprotein lipase (LPL) is a major regulator of triglyceride clearance. A genetic variant of the LPL gene on chromosome 8p22, Asn291Ser, has previously been associated with dyslipidaemia and an increased frequency of cardiovascular disease as well as familial disorders of lipoprotein metabolism. The aim of this study was to test whether the phenotypic expression of the LPL Asn291Ser variant is dependent upon glucose tolerance and insulin resistance. Therefore, the Asn291Ser variant was examined in 192 patients with Type 2 diabetes, 278 subjects with normal glucose tolerance who are first degree relatives of patients with Type 2 diabetes and 226 healthy control spouses without family history of diabetes.

Methods  The subjects were genotyped with an allele‐specific mini‐sequencing method. Insulin resistance was estimated using the homeostasis model assessment (HOMA) index.

Results   The frequency of the Asn/Ser genotype was significantly increased in normoglycaemic subjects with hypertriglyceridaemia (> 1.7 mmol/l), and was associated with dyslipidaemia and increased systolic blood pressure. There was a significant interaction between Asn291Ser and insulin resistance in normoglycaemic subjects, indicating that dyslipidaemia is more severe in Asn/Ser carriers with reduced insulin sensitivity. The frequency of the Asn/Ser genotype was not increased in diabetic subjects with hypertriglyceridaemia, but was associated with increased systolic blood pressure.

Conclusions   The Asn/Ser genotype of the LPL gene is associated with dyslipidaemia in normoglycaemic subjects, and the dyslipidaemic phenotype is more severe in insulin‐resistant subjects. This association is not seen in diabetic subjects.
Autoantibodies to glutamic acid decarboxylase in diabetic patients from a multi‐ethnic Australian community: the Fremantle Diabetes Study
Authors: Davis T. M. E. , Zimmet P. , Davis W. A. , Bruce D. G. , Fida S. , Mackay I. R.
Published: March 2003

SUMMARY

Aims  To investigate ethnic/racial differences in the prevalence of serum antibodies to glutamic acid decarboxylase (GADA) and ICA512/IA‐2 in diabetic patients from a large, urban community.

Methods  A cross‐sectional sample of 1381 diabetic patients aged 11–98 years, representing 61% of those identified in a postcode‐defined population base of 120 097 people were studied. Diabetes was classified on clinical grounds. Serum GADA and anti‐ICA512/IA‐2 were measured by radioimmuno‐precipitation assay.

Results  Anglo‐Celts formed 62% of the sample, southern Europeans 18%, other Europeans 8% and Asians 3%. GADA prevalence in Type 1 and Type 2 diabetes mellitus was 46.0% and 4.2%, respectively, amongst Anglo‐Celts and 22.2% and 1.7% in southern Europeans. The prevalence of anti‐ICA512/IA‐2 in Type 1 diabetes was 17.4% and, in a sample of 233 patients with Type 2 diabetes, 0.8%. GADA‐positive Type 2 patients had a lower body mass index and greater glycosylated haemoglobin, and were more likely to be taking insulin, than GADA‐negative Type 2 diabetic subjects (P < 0.05), consistent with the phentoype of latent autoimmune diabetes of adults (LADA). In both Type 1 and Type 2 diabetes, there was a strong inverse association between GADA and serum triglycerides (P < 0.001).

Conclusions  The relatively low GADA prevalence in Anglo‐Celt patients with Type 1 diabetes is a feature of this community‐based study and suggests that GADA levels do fall with time, given the older age of the sample and a relatively long period between diagnosis and sampling. Southern Europeans had an even lower GADA prevalence, regardless of diabetes type. Variations in GADA frequency in diabetic patients of differing European ethnicity has implications for clinical management and healthcare planning.
Predictors of mortality and end‐stage diabetic complications in patients with Type 1 diabetes mellitus on intensified insulin therapy
Authors: Mühlhauser I. , Overmann H. , Bender R. , Jörgens V. , Berger M.
Published: March 2003

SUMMARY

Aims To assess predictors of mortality and end‐stage diabetic complications in patients with Type 1 diabetes mellitus on intensified insulin therapy.

Methods A cohort of 3674 patients (insulin treatment before age 31) who had participated in a 5‐day in‐patient group treatment and teaching programme for intensification of insulin therapy between 9/1978 and 12/1994 were re‐assessed after 10 ± 3 (mean ± sd) years.

Results Vital status and data on blindness, amputations, and renal replacement therapy were documented for 97% patients; 7% patients had died, 1.3% had become blind, 2% had amputations and 4.6% started renal replacement therapy. Using the Cox proportional hazards model, the following risk factors of mortality as assessed at baseline were identified: nephropathy (at least macroproteinuria), hazard ratio 3.8 (95% confidence interval 2.6–5.6); smoking, 1.9 (1.4–2.6); diabetes duration, 1.5 (1.2–1.8) for a difference of 10 years; serum cholesterol, 1.1 (1.0–1.2) for a difference of 1 mmol/l; lower social status, 1.4 (1.1–1.8) for a difference of 1 out of 3 levels; age, 1.3 (1.1–1.6) for a difference of 10 years; male sex, 1.4 (1.1–1.9); systolic blood pressure, 1.1 (1–1.2) for a difference of 10 mmHg. For the combined endpoint – blindness or amputations or renal replacement therapy – predictors were: nephropathy, foot complications, HbA1c, smoking, cholesterol, systolic blood pressure, retinopathy, hypertension, and social status.

Conclusion In Type 1 diabetic patients who start intensified insulin therapy, nephropathy remains the strongest predictor of mortality and end‐stage complications. Glycosylated haemoglobin is a risk factor of end‐stage complications but not of mortality. Conventional risk factors comparable to the general population, particularly smoking become operative as predictors of both mortality and end‐stage complications.
Coronary heart disease risk assessment in diabetes mellitus–‐a comparison of PROCAM and Framingham risk assessment functions
Authors: Game F. L. , Jones A. F.
Published: March 2003

Aims  To assess any differences between coronary heart disease (CHD) risks calculated by the Framingham equation and those calculated by the PROCAM equation in men with and without diabetes mellitus, and whether any such differences are associated with the hypertriglyceridaemia of diabetes mellitus.

Methods  Clinical and biochemical data collected from 1774 men seen in either general practice, a hospital diabetes or lipid clinic. CHD risks were calculated by both the Framingham and PROCAM functions and comparisons made between those patients with and those without diabetes.

Results  Of the 1774 men only 996 fulfilled the criteria for assessment by the PROCAM equation and thus further analysis. Patients with diabetes mellitus had significantly higher serum triglyceride levels than those without (1.9 mmol/l vs. 1.7 mmol/l). Median annual CHD risks calculated by the Framingham function were 1.7% in the patients with and 1.32% in the patients without diabetes mellitus, whereas those calculated by the PROCAM function were 0.77% and 0.6%, respectively. Bland–Altman difference plots showed that in both groups of patients the PROCAM equation systematically underestimated risk in comparison with the Framingham equation at low levels of risk but overestimated at higher levels of risk. The shape of the plots in each group of patients was, however, similar.

Conclusion  There were no systematic differences between CHD risks calculated by the two different equations in patients with diabetes compared with those without, despite the higher serum triglyceride levels associated with diabetes. Restrictions in the use of the PROCAM function meant that only 56% of the original cohort could be assessed in this way. Thus the Framingham equation remains the most suitable method of CHD risk prediction for UK patients with and without diabetes mellitus.
Normalization of pregnancy outcome in pregestational diabetes through functional insulin treatment and modular out‐patient education adapted for pregnancy
Authors: Howorka K. , Pumprla J. , Gabriel M. , Feiks A. , Schlusche C. , Nowotny C. , Schober E. , Waldhoer T. , Langer M.
Published: March 2003

Aim  To investigate whether modular out‐patient group education for flexible, Functional Insulin Treatment (FIT) adapted for pregnancy can eliminate diabetes‐associated neonatal complications in pregestational diabetes.

Research design and methods  Outcome analysis of the modular out‐patient group education and FIT based on separate insulin dosages for fasting, eating or correcting hyperglycaemia in 76 consecutive pregnancies (in 20 cases first after conception) of 59 patients with pregestational diabetes (Type 1 diabetes, n = 54). Controls: (a) diabetic pregnancies: historical controls; (b) non‐diabetic pregnancies: retrospective case‐controlled study; (c) population‐based data of all Austrian newborns registered within the respective time period.

Results  HbA1c of 113 ± 18% of mean value (= 100%) of non‐diabetic, non‐pregnant population (103 ± 14% during the last pregnancy trimester), and self‐monitored blood glucose of 5.6 ± 0.7 mmol/l (5.3 ± 0.7 mmol/l during the last trimester) was achieved throughout all FIT pregnancies. Severe hypoglycaemia occurred in 14 pregnancies. The gestational age at delivery was 39.2 ± 1.5 weeks (four cases (5.4%) < 37 weeks) with a birth weight of 3305 ± 496 g. Four newborns (5.3%) were above the 90th, and nine (11.8%) below the 10th percentile for weight of reference population‐based data. Hypoglycaemia was recorded in six newborns (8%). Malformations were found in two infants whose mothers booked for diabetes FIT education only after conception. The caesarean delivery rate was 25%. In comparison with historical diabetic pregnancy controls we demonstrated a reduction in major complications, and compared with non‐diabetic women, a lowering of diabetes‐related neonatal complication rates to general population levels.

Conclusions  Structured, comprehensive, modular out‐patient group education promoting self‐choice of insulin dose for flexible, normal eating prior to conception normalizes pregnancy outcome in diabetes.

Diabet. Med. 18, 965–972 (2001)
Maternal transmission of diabetes
Authors: Alcolado J. C. , Laji K. , Gill‐Randall R.
Published: March 2003

Type 2 diabetes mellitus represents a heterogeneous group of conditions characterized by impaired glucose homeostasis. The disorder runs in families but the mechanism underlying this is unknown. Many, but not all, studies have suggested that mothers are excessively implicated in the transmission of the disorder. A number of possible genetic phenomena could explain this observation, including the exclusively maternal transmission of mitochondrial DNA (mtDNA). It is now apparent that mutations in mtDNA can indeed result in maternally inherited diabetes. Although several mutations have been implicated, the strongest evidence relates to a point substitution at nucleotide position 3243 (A to G) in the mitochondrial tRNAleu(UUR) gene. Mitochondrial diabetes is commonly associated with nerve deafness and often presents with progressive non‐autoimmune β‐cell failure. Specific treatment with Coenzyme Q10 or L‐carnitine may be beneficial. Several rodent models of mitochondrial diabetes have been developed, including one in which mtDNA is specifically depleted in the pancreatic islets. Apart from severe, pathogenic mtDNA mutations, common polymorphisms in mtDNA may contribute to variations of insulin secretory capacity in normal individuals. Mitochondrial diabetes accounts for less than 1% of all diabetes and other mechanisms must underlie the maternal transmission of Type 2 diabetes. Possibilities include the role of maternally controlled environments, imprinted genes and epigenetic phenomena.
Predictivity of thyroid autoantibodies for the development of thyroid disorders in children and adolescents with Type 1 diabetes
Authors: Kordonouri O. , Deiss D. , Danne T. , Dorow A. , Bassir C. , Grüters‐Kieslich A.
Published: March 2003

Aims To investigate the prevalence of thyroid autoantibodies and their significance for the development of thyroid disorders in children and adolescents with Type 1 diabetes.

Methods Antibodies to thyroglobulin (anti‐TG) and thyroperoxidase (anti‐TPO) were measured in 216 patients (113 boys; median age 12.9 years (range 1–22 years)) with Type 1 diabetes (diabetes duration 2.5 years (0–14 years)) in a cross‐sectional study. Sixteen patients with significantly elevated anti‐TPO titres were followed longitudinally (6.0 years (4–13 years)) including the measurement of anti‐TPO, anti‐TG, T3, T4, thyroid‐stimulating hormone (TSH) and ultrasound assessment.

Results Twenty‐two patients (10.0%) had significantly elevated titres of anti‐TPO, 19 (8.7%) of anti‐TG and 13 (5.9%) of both autoantibodies. Girls had more frequently elevated anti‐TPO antibodies than boys (P < 0.05). Eight of 16 patients (50%) developed thyroid disorders defined by a TSH elevation (≥ 4.5 µU/ml) and/or sonographic thyroid abnormalities during a median time of 3.5 years (2–6 years) after first detection of anti‐TPO positivity. They were characterized by higher levels of anti‐TPO (P = 0.001) and a more frequent coexistence of anti‐TG antibodies (P = 0.002) than those with no development of thyroid disorder even after an observation period of 5.5 years (5–10 years).

Conclusions Because 50% of children with diabetes and significant titres of anti‐TPO develop thyroid problems within 3–4 years, examinations of thyroid antibodies should be performed yearly. In cases of significant antibody titres, thyroid function tests and ultrasound assessment are recommended in order to minimize the risk of undiagnosed hypothyroidism in these patients.
Charcot neuroarthropathy of the knee in Type 1 diabetes: treatment with total knee arthroplasty
Authors: Lambert A. P. , Close C. F.
Published: March 2003

Background Charcot neuroarthropathy is well recognized in diabetes, although it typically affects the joints of the forefoot and ankle. Neuroarthropathy affecting the knee in diabetes is extremely rare. The surgical options for treatment of Charcot neuroarthropathy remain poorly defined, particularly the use of arthroplasty with knee involvement.

Methods We describe a case of neuroarthropathy of the knee in a patient with Type 1 diabetes. We also describe the successful management of the disorder with total knee arthroplasty—only the third such description.

Results The case illustrates some of the typical radiological features of this uncommon condition, which may aid early diagnosis and limit morbidity.
Continuous intraperitoneal insulin infusion in patients with ‘brittle’ diabetes: favourable effects on glycaemic control and hospital stay
Authors: DeVries J. H. , Eskes S. A. , Snoek F. J. , Pouwer F. , Van Ballegooie E. , Spijker A. J. , Kostense P. J. , Seubert M. , Heine R. J.
Published: March 2003

Aims To evaluate the effects of continuous intraperitoneal insulin infusion (CIPII) using implantable pumps on glycaemic control and duration of hospital stay in poorly controlled ‘brittle’ Dutch diabetes patients, and to assess their current quality of life.

Methods Thirty‐three patients were included. Glycaemic control was retrospectively assessed with HbA1c levels acquired before implantation, 1 year later and at long‐term follow up of 58 months. Duration of hospital stay the year before and the year following first implantation was extracted from hospital records. Determinants of long‐term glycaemic response were sought. Self‐report questionnaires were administered at 58 months follow‐up only, to assess current psychopathology and quality of life.

Results Mean HbA1c decreased from 10.0 ± 2.3% to 9.0 ± 1.8% (P = 0.039) 1 year after implantation and stabilized at 9.0 ± 1.6% (P = 0.023) during long‐term follow‐up. Median number of hospital days in the 20 patients suffering from hospital admission before implantation decreased from 45 the year before implantation to 13 the year after (P = 0.005). Patients with a higher baseline HbA1c showed a larger long‐term response (P < 0.001). Relatively low levels for quality of life were found, as well as a higher than expected number of patients with psychiatric symptoms.

Conclusions CIPII proved effective in complex patients with a history of poor control and hospital admission. Despite a substantial long‐term improvement in glycaemic control and diminished hospital stay, normal levels of glycaemic control and quality of life were not attained.
Physical activity and cause‐specific mortality in men with Type 2 diabetes/impaired glucose tolerance: evidence from the Whitehall study
Authors: Batty G. D. , Shipley M. J. , Marmot M. , Davey Smith G.
Published: March 2003

AimsGiven that studies of individuals with Type 2 diabetes or impaired glucose tolerance indicate that physical activity has a normalizing effect on several indices of coronary heart disease (CHD) risk—including body weight, blood pressure, blood lipids, and cardiorespiratory fitness—it is plausible that activity may reduce CHD incidence in this group in the long term. The aim of the present analysis was to explore this hypothesis using data from a prospective observational study.

MethodsWe examined the relation of two indices of physical activity—walking pace and leisure activity—to total mortality, CHD, and other cardiovascular diseases in a 25‐year follow‐up of 6408 male British Civil Servants who underwent an oral glucose tolerance test at study entry.

ResultsIn 352 men who were identified as having Type 2 diabetes or impaired glucose tolerance (diabetes/IGT) at baseline, 215 had died at follow‐up and, in 6056 normoglycaemics, 2550 deaths had occurred. The two indices of physical activity were inversely related to all‐cause, CHD, and other cardiovascular disease mortality in both normoglycaemics and in men with diabetes/IGT. Although these associations were attenuated somewhat after statistical adjustment for a range of covariates, the majority held, suggesting an independent effect for physical activity. The gradient of the activity–mortality association was steeper in individuals with diabetes/IGT in comparison with the normoglycaemics, with the linear trend across activity levels for CHD risk differing markedly in the analyses of both walking pace (P‐value for interaction test = 0.05) and leisure activity (P‐value = 0.02).

ConclusionsThe findings of the present analysis of men with Type 2 diabetes/IGT provide support for those from a small number of other studies of persons with Type 2 diabetes suggesting that this group may benefit from physical activity in terms of CHD risk reduction.
A family history of Type 2 diabetes is associated with increased plasma levels of C‐reactive protein in non‐smoking healthy adult women
Authors: Pannacciulli N. , De Pergola G. , Giorgino F. , Giorgino R.
Published: March 2003

Aims The aim of our study was to test whether a family history of Type 2 diabetes (FH) in women is associated with plasma C‐reactive protein (CRP).

Methods CRP plasma levels were measured in 162 women, aged 18–60 years; 95 had a positive family history of Type 2 diabetes in a parent or grandparent (FH+), and 67 gave no family history of this disease (FH−). Other measurements included: central fat accumulation, as evaluated by waist circumference; insulin resistance, as calculated by homeostatic model assessment (HOMAIR); systolic and diastolic blood pressure; and fasting concentrations of glucose, insulin, and lipids.

Results CRP plasma levels were significantly higher in FH+ than in FH− subjects. Moreover, CRP was independently associated with age, body mass index, waist circumference, HOMAIR, and FH.

Conclusions Our study, performed in a selected population of women free from well‐known risk factors for atherothrombosis, demonstrates that subjects with a family history of Type 2 diabetes have higher CRP plasma levels than age‐ and BMI‐matched controls with no family history. Our results show that a family history of Type 2 diabetes is an independent contributor of CRP concentrations, in addition to age, total fatness, central fat accumulation, and insulin resistance.

Diabet. Med. 19, 689–692 (2002)
Ambulatory blood pressure monitoring: is it necessary for the routine assessment of hypertension in people with diabetes?
Authors: Strachan M. W. J. , Gough K. , McKnight J. A. , Padfield P. L.
Published: March 2003

Aims The British Hypertension Society (BHS) has recommended that, for people with diabetes, the target ‘clinic’ blood pressure should be < 140/80 mmHg. Ambulatory monitoring of blood pressure (ABPM) is used widely in the assessment of hypertension and the BHS has recommended that the target ‘awake’ ambulatory blood pressure for people with diabetes should be < 130/75 mmHg. The purpose of the present study was to determine the utility of ABPM in the assessment of hypertension in patients with diabetes, over and above a careful ‘clinic’ measurement of blood pressure.

Methods The records of 540 patients with diabetes who underwent ABPM (using SpaceLabs monitors) were retrospectively analysed. With respect to current BHS recommendations, the positive and negative predictive values of ‘clinic’ blood pressure (measured by trained nurses using mercury sphygmomanometers) on ‘awake’ ambulatory blood pressure (ABP) were calculated.

Results The positive predictive value of the ‘clinic’ BP, its ability to detect patients whose ABP was above BHS targets, was 99%. The negative predictive value of ‘clinic’ blood pressure was 27%.

Conclusions With regard to current BHS guidelines, ABPM is generally unnecessary in the assessment of hypertension in patients with diabetes, provided careful ‘clinic’ measurements of blood pressure are made.
The evaluation of screening policies for diabetic retinopathy using simulation
Authors: Davies R. , Roderick P. , Canning C. , Brailsford S.
Published: March 2003

Aims To develop a model for evaluating screening strategies and to use it to determine the cost effectiveness of varying the screening method and the screening interval.

Methods A discrete event simulation was designed, validated and run for a population of 500 000. Most parameters were derived from peer‐reviewed publications.

Results Standard methods of screening save up to 50% of the potential sight years lost. They give up to 85% of the sight years saved by an idealized gold standard programme using mydriatic seven‐field photography reported by an ophthalmologist. The mobile camera, used for annual screening and 6‐month follow‐up after the detection of background retinopathy, had an estimated cost of £449 200 per year with £2842 per sight year saved. It is less efficient to screen Type 2, rather than Type 1 diabetes mellitus patients, but they contributed to almost three‐quarters of the sight years saved.

Conclusions The model can evaluate screening intervals and methods on a national or health authority basis. Results indicate that it appears more cost effective to continue to screen outside an ophthalmology clinic, until treatment is needed. Programmes with annual screening, and more frequent screening for those with background retinopathy, are robust to realistic fluctuations in compliance and screening sensitivity.
Longitudinal assessment of the development of diabetic polyneuropathy and associated risk factors
Authors: Van De Poll‐Franse L. V. , Valk G. D. , Renders C. M. , Heine R. J. , Van Eijk J. T. M.
Published: March 2003

Aims To longitudinally assess risk factors for diabetic polyneuropathy (DPN) severity, and to longitudinally assess risk factors for the change of DPN severity during 2–4 years of follow‐up.

Methods From 1995 to 1999, 486 Type 2 diabetes patients in general practice were examined annually with regard to DPN severity and its possible risk factors. DPN severity was assessed with a clinical neurological examination (CNE) which included pinprick sense, light touch sense, vibration sense and ankle jerk. Longitudinal (multivariate) linear associations of (change of) CNE score and predicting variables were analysed using multilevel analyses.

Results In this population, 50% of participants were men and had a mean age of 65.4 years, almost one‐third (31.7%) of the participants had a CNE score > 4 at baseline and were classified with DPN. CNE score significantly increased during follow‐up. Among participants not graded with DPN at baseline, 21.3% progressed towards a CNE score > 4 after 3 years of follow‐up. Longitudinal multivariate analyses showed that age, diabetes duration, HbA1c, height, body mass index and ankle‐arm index together best predicted CNE score during follow‐up. Change of CNE score during follow‐up was best predicted by age, diabetes duration and HbA1c, with the latter being the strongest predictor.

Conclusions Although several factors are longitudinally associated with DPN, HbA1c, age and diabetes duration were the best predictors of CNE change during follow‐up. Therefore, improving glycaemia remains an important amenable factor in preventing worsening of diabetic polyneuropathy.
Does direct ophthalmoscopy improve retinal screening for diabetic eye disease by retinal photography?
Authors: Leese G. P. , Ellis J. D. , Morris A. D. , Ellingford A.
Published: March 2003

Aims To identify whether after performing retinal photography, direct ophthalmoscopy can improve the yield of screening for the detection of sight‐threatening diabetic eye disease (STDED).

Methods Patients (n   =  408) who had previously received both dilated direct ophthalmoscopy by a diabetologist and retinal photography graded by a diabetologist within 3 months of each other were included. The results of the other screening modality were not available to the grader/screener. The first 308 patients were consecutive attendees at the clinic who fulfilled the study criteria and 100 were selected because they were identified as having potential STDED by either one of these modalities. An ophthalmologist using slit lamp biomicroscopy then examined patients identified with potential STDED.

Results In 357 (88%) patients there was agreement between the two modalities about whether referral to an ophthalmologist was required (κ 0.62). Retinal photography identified 38 patients for referral to ophthalmology which ophthalmoscopy missed. Of these, the ophthalmologist agreed that STDED was present in 32 (84%) and four patients required early laser. Ophthalmoscopy identified 13 patients for referral who were not identified by photography. Of these, the ophthalmologist agreed with the diabetologist that STDED was present in seven (54%) and one patient required early laser.

Conclusion Ophthalmoscopy may identify the occasional patient with diabetes who has STDED which is missed by retinal photography. For a systematic retinal screening programme, adding ophthalmoscopy to retinal photography will increase false‐positive referrals and is likely to detect only a few extra patients requiring laser.
Metabolic and immunogenetic prediction of long‐term insulin remission in African patients with atypical diabetes
Authors: Sobngwi E. , Vexiau P. , Levy V. , Lepage V. , Mauvais‐Jarvis F. , Leblanc H. , Mbanya J. C. , Gautier J. F.
Published: March 2003

Aims We aimed to characterize a cohort of ‘atypical’ diabetic patients of sub‐Saharan African origin and to analyse possible determinants of long‐term remission.

Methods Over 6 years, we studied the clinical and therapeutic profile of 42 consecutive patients undiagnosed or untreated prior to inclusion presenting with cardinal features of diabetes mellitus. We measured insulin secretion and sensitivity at inclusion. Immunogenetic (anti‐GAD, anti‐ICA and HLA class II) markers of Type 1 diabetes were compared with a 90‐non‐diabetic unrelated adult African population.

Results Twenty‐one ketonuric patients (age 42 ± 9 (sd) years; body mass index (BMI) 26 
±
 3 kg/m2) were initially insulin‐treated (IT), and 21 non‐ketonuric patients (age 38 
±
 8 years; BMI 26 
±
 5 kg/m2) had oral and/or diet therapy (NIT). Insulin could be discontinued in 47.6% (10/21) IT with adequate glycaemic control (HbA1c 6.7 
±
 1.3%), while insulin was secondarily started in 38.1% (8/21) NIT in expectation of better control. The initial basal (odds ratio (OR) 9.1, 95% confidence interval (CI) 1.3–64.4) and stimulated C‐peptide (OR 8.17, 95% CI 1.5–44.1) were independently associated with remission. Insulin resistance was present in all the groups, more marked in the insulin‐treated NIT. Anti‐GAD antibodies and ICA were rare, but 38.1% IT vs. 1.1% controls had Type 1 diabetes HLA susceptibility haplotypes (P  < 0.001) without significant difference between the subgroups.

Conclusion Prolonged discontinuation of insulin is frequent in African diabetic patients initially presenting with signs of insulinopenia. In our patients, long‐term insulin therapy was not associated with immunogenetic markers of Type 1 diabetes. The initial measure of insulin secretion seemed a good predictor of long‐term remission.
Tissue factor pathway inhibitor (TFPI) release after heparin stimulation is increased in Type 1 diabetic patients with albuminuria
Authors: Leurs P. B. , Van Oerle R. , Hamulyak K. , Wolffenbuttel B. H. R.
Published: March 2003

Aims To study heparin‐stimulated TFPI release in relation to complications in Type 1 diabetic patients.

Subjects and methods Nineteen uncomplicated Type 1 diabetic patients (group I) were compared with 18 patients with retinopathy (group II), and nine patients with retinopathy and albuminuria (group III). Blood samples were taken before (basal) and till 30 min after 5000 IU of heparin i.v. (post‐heparin). TFPI activity was measured chromogenically. Von Willebrand factor, tissue plasminogen activator (t‐PA), plasminogen activator inhibitor‐1 (PAI‐1) and thrombomodulin were also measured.

Results Basal TFPI activity was higher in group III (121 ± 10%) compared with group II (111 ± 8%) or group I (110 ± 13%) (P < 0.05), and strongly correlated with albuminuria (r = 0.66, P < 0.05). At all time points after heparin administration, TFPI activity in group III was significantly higher than in group I. TFPI activity was also higher in group III than in group II 5–30 min post‐heparin. The increase in post‐heparin TFPI activity, measured as the incremental area under the curve, was higher in group III compared with group I (65 ± 7 vs. 59 ± 4; P < 0.05). Of the other parameters, only thrombomodulin was higher in group III (44 ± 24 vs. 26 ± 7 (group II) and 28 ± 9 ng/ml (group I); P < 0.01).

Conclusions We conclude that basal and post‐heparin TFPI activity is increased in albuminuric patients. The increase in heparin‐stimulated TFPI release in patients with albuminuria is higher than in patients with retinopathy or without complications. This could be the result of altered endothelial glycosaminoglycan characteristics.

Diabet. Med. 20, 16–22 (2003)