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Rationale: Diabetic peripheral neuropathy is common and causes significant morbidity. Obstructive sleep apnea (OSA) is also common in patients with type 2 diabetes. Because OSA is associated with inflammation and oxidative stress, we hypothesized that OSA is associated with peripheral neuropathy in type 2 diabetes.Objectives: To assess the relationship between OSA and peripheral neuropathy in patients with type 2 diabetes.Methods: A cross-sectional study of adults with type 2 diabetes recruited randomly from the diabetes clinic of two UK hospitals.Measurements and Main Results: Peripheral neuropathy was diagnosed using the Michigan Neuropathy Screening Instrument. OSA (apnea-hypopnea index ≥ 5 events/h) was assessed using home-based, multichannel respiratory monitoring. Serum nitrotyrosine was measured by ELISA, lipid peroxide by spectrophotometer, and microvascular function by laser speckle contrast imaging. Two hundred thirty-four patients (mean [SD] age, 57 [12] yr) were analyzed. OSA prevalence was 65% (median apnea-hypopnea index, 7.2; range, 0-93), 40% of which were moderate to severe. Neuropathy prevalence was higher in patients with OSA than those without (60% vs. 27%, P < 0.001). After adjustment for possible confounders, OSA remained independently associated with diabetic neuropathy (odds ratio, 2.82; 95% confidence interval, 1.44-5.52; P = 0.0034). Nitrotyrosine and lipid peroxide levels (n = 102, 74 with OSA) were higher in OSA and correlated with hypoxemia severity. Cutaneous microvascular function (n = 71, 47 with OSA) was impaired in OSA.Conclusions: We describe a novel independent association between diabetic peripheral neuropathy and OSA. We identified increased nitrosative/oxidative stress and impaired microvascular regulation as potential mechanisms. Prospective and interventional studies are needed to assess the impact of OSA and its treatment on peripheral neuropathy development and progression in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to compare prevalence and risk factors for diabetic retinopathy among U.K. residents of South Asian or white European ethnicity.Research Design and Methods: This was a community-based cross-sectional study involving 10 general practices; 1,035 patients with type 2 diabetes were studied: 421 of South Asian and 614 of white European ethnicity. Diabetic retinopathy, sight-threatening retinopathy, maculopathy, and previous laser photocoagulation therapy were assessed after grading of retinal photographs. Data were collected on risk factors including age, duration, and treatment of diabetes, blood pressures, serum total cholesterol, and A1C.Results: Patients of South Asian ethnicity had significantly higher systolic (144 vs. 137 mmHg, P < 0.0001) and diastolic (84 vs. 74 mmHg, P < 0.0001) blood pressure, A1C (7.9 vs. 7.5%, P < 0.0001), and total cholesterol (4.5 vs. 4.2 mmol/l, P < 0.0001). Diabetic retinopathy was detected in 414 (40%) patients (189 South Asian [45%] versus 225 white European [37%]; P = 0.0078). Sight-threatening retinopathy was detected in 142 (14%) patients (68 South Asian [16%] versus 74 white European [12%]; P = 0.0597). After adjustment for confounders, there were significantly elevated risks of any retinopathy and maculopathy for South Asian versus white European patients.Conclusions: Patients of South Asian ethnicity had a significantly higher prevalence of diabetic retinopathy and maculopathy, with significantly elevated systolic and diastolic blood pressure, A1C, and total cholesterol; lower attained age; and younger age at diagnosis. Earlier onset of disease and higher levels of modifiable risk factors make early detection of diabetes, annual referral for retinal screening, and intensive risk factor control key elements in addressing this health inequality. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tight glycaemic control in people with type 2 diabetes can lead to a reduction in microvascular and possibly macrovascular complications. The use of near-patient (rapid) testing offers a potential method to improve glycaemic control. AIM: To assess the effect and costs of rapid testing for glycated haemoglobin (HbA1c) in people with type 2 diabetes. DESIGN OF STUDY: Pragmatic open randomised controlled trial. SETTING: Eight practices in Leicestershire, UK. METHOD: Patients were randomised to receive instant results for HbA1c or to routine care. The principal outcome measure was the proportion of patients with an HbA1c <7% at 12 months. We also assessed costs for the two groups. RESULTS: Of the 681 patients recruited to the study 638 (94%) were included in the analysis. The mean age at baseline was 65.7 years (SD = 10.8 years) with a median (interquartile range) duration of diabetes of 4(1-8) years. The proportion of patients with HbA1c < 7% did not differ significantly between the intervention and control groups (37 versus 38%, odds ratio 0.95 [95% confidence interval = 0.69 to 1.31]) at 12 months follow up. The total cost for diabetes-related care was 390 UK pounds per patient for the control group and 370 UK pounds for the intervention group. This difference was not statistically significant. CONCLUSION: Near-patient testing for HbA1c alone does not lead to outcome or cost benefits in managing people with type 2 diabetes in primary care. Further research is required into the use of rapid testing as part of an optimised patient management model including arrangements for patient review and testing. [ABSTRACT FROM AUTHOR]

AIMS: We tested the hypothesis that enhanced care for diabetes, tailored to the needs of the South Asian community with Type 2 diabetes, would improve risk factors for diabetic vascular complications and ultimately reduce morbidity and mortality. PATIENTS AND METHODS: The study was a cluster randomized controlled trial (RCT) with general practice the unit of randomization. Six West Midlands general practices with a high proportion of South Asian patients were randomized to 'enhanced care' using Asian link workers and extra community diabetes specialist nurse sessions (intervention) or continued standard practice care (control). RESULTS: Of 401 patients recruited to the study, 361 (90%), comprising 178 from Coventry and 183 from Birmingham were eligible and included in the analyses. The mean age at baseline (standard deviation, SD) was 58.9 (11.7 years) with median (interquartile range; IQR) duration of diabetes 6.5 (3-11) years. At one year follow-up there was a significant difference in reduction of systolic (4.6 mmHg, P = 0.035) and diastolic blood pressure (3.4 mmHg, P = 0.003) and total cholesterol (0.4 mmol/l, P = 0.005), comparing the intervention and control groups. After adjusting for baseline measurement and age, only differential reduction in diastolic blood pressure remained significant. There was no significant change in HbA(1c) and no difference between the groups. CONCLUSIONS: Using link workers and extra community diabetes specialist nurse input together with treatment protocols in primary care might prove a useful strategy in working towards NSF targets for diabetes management. In this study, small reductions in blood pressure and cholesterol were achieved. Improvement in glycaemic control may require longer and possibly different strategies. Further research is required to evaluate fully the effectiveness, including the costs and longer term sustainability of culturally sensitive initiatives. [ABSTRACT FROM AUTHOR]

Background: The Heartbeat Award scheme (HBA) was initiated in Leicestershire in 1990. An evaluation of compliance of HBA premises with nutrition criteria and an assessment of the impact of the scheme on food purchasing trends has not been previously reported. Method: Twenty-three caterers (12 workplaces and 11 public eating places) responsible for implementing the scheme were interviewed to establish the extent to which premises continued to comply with nutrition criteria; whether healthy food choices were being marketed after receiving the HBA; and caterers assessment of food purchasing trends. Data were collected during face-to-face interviews using a questionnaire and checklist. Results: All workplaces complied with 11 of the 34 nutrition criteria, and all public eating places complied with 22 of the 34 nutrition criteria. A quarter of caterers reported not providing one-third of all menu sections as healthy choices. Three-quarters of establishments used a symbol to highlight healthy food choices. This was the only form of promotion in most cases. At least a quarter of premises reported an increase in sales of some healthier food items. Even so, the uptake of less healthy choices remained the same in most premises. Conclusion: The lack of compliance locally with so many nutrition criteria is a major concern. This raises the question of whether scarce dietetic resources are being used appropriately without a system for monitoring. [ABSTRACT FROM AUTHOR]

The prevalence of chronic renal failure (CRF) in people with diabetes mellitus is unknown. This study was undertaken to determine the prevalence of CRF in Leicestershire residents with or without diabetes mellitus in 1991. All serum creatinine values over 200 micromol/l in 1991 were abstracted from the computer records of the central laboratory serving Leicestershire residents (total population 867,521; Indo-Asians 8.9%). Those with serum creatinine persistently raised (>200 micromol/l but <500 micromol/l) were classified as having CRF. Those with serum creatinine >500 micromol/l or who were on dialysis or had been transplanted, were classified as end stage renal failure (ESRF). Those with diabetes were identified from the central diabetes register, dialysis register and consultants' notes with 100% ascertainment. The prevalence of CRF varied from 0.3/1000 (95% CI 0.2-0.4/1000) in non-diabetic non-Asian females aged 0-44 years to 25.2/1000 (95% CI 9.3-54.0/1000) in diabetic Asian males, aged >65 years. Multivariate logistic modelling indicated that Asians and males had approximately twice the CRF prevalence of White Caucasians and females respectively, irrespective of diabetes or age. The prevalence of CRF increased with age, and having diabetes increased the CRF prevalence five-fold in the 0-44 age group, irrespective of ethnicity or sex. The effect of diabetes was not evident in the older age groups. These findings have important implications for the use and allocation of health care resources. [ABSTRACT FROM AUTHOR]

Background: Understanding the outcomes and risks for live kidney donors (LD) is increasingly important; this study investigated all-cause mortality and morbidity outcomes of LD compared with a healthy cohort., Methods: Live donor dataset was obtained from the UK Transplant Registry and a comparator nondonor cohort selected from The Health Improvement Network (THIN) database, a UK primary healthcare database. All LD from January 1, 2001, to December 31, 2013, were included, with follow-up until December 31, 2016., Results: There were 9750 LD and 19 071 THIN participants. Median follow-up (interquartile range) for LD was 8.4 (6.0-11.3) years and for THIN was 5.4 (2.6-8.5) years. In up to 15 years, follow-up end-stage renal disease was observed in 1 LD versus 7 THIN (P = 0.280). Nine LD had estimated glomerular filtration rate of <30 mL/min/1.73 m versus 43 in THIN (P = 0.012), but no statistically significant difference in adjusted logistic regression analyses. Risk of diabetes mellitus, depression, and cardiovascular disease was significantly higher for THIN cohort in adjusted analyses. The risk of hypertension was higher for LD at 5 years but was not significantly different in fully adjusted analyses at 10 years. There were 68 deaths in LD and 485 in THIN over the follow-up period, with significant difference in mortality favoring LD (P < 0.001)., Conclusions: The medium-term morbidity and mortality outcomes of live donors in comparison with a healthy cohort suggest that live donation is not associated with excess mortality, end-stage renal disease, or morbidity, in at least 10 years follow-up.

Background: Early onset of type 2 diabetes (T2DM) is associated with prolonged exposure to hyperglycaemia and increased propensity to chronic complications. The aim of this study was to characterize and compare the phenotypic characteristics and risk factors in a multi-ethnic cohort of young adults with type 2 diabetes (T2DMY). Methods: One hundred young adults (White European [WE], South Asian [SA] and African-Caribbean [AC]) diagnosed with T2DM before the age of 40 years were recruited. Demographics, family history, diabetes related complications, co-morbidities, anthropometry (body mass index [BMI], body composition), physical activity and biochemistry (HbA1c, lipid profile, liver and renal function) and autoantibodies (anti GAD, anti islet cell) were collected for all participants. Data were analysed for the most represented ethnic groups: (WE, N =  36 and SA, N =  53) using SPSS version 23. Results: Mean (± standard deviation) age at diagnosis was 32.5 ± 5.5 years and mean diabetes duration was 7.7 ± 3.8 years. Overweight/obesity was present in 95% of participants, history of maternal diabetes in 68%, deprivation 75%, low physical activity 40%, polycystic ovarian disease 29% (in females), acanthosis nigricans 12% and non-alcoholic fatty liver 11%. There was considerable clustering of risk factors within the cohort with over 75% of all subjects having three or more of the above risk factors and 52% required insulin within 3 years of diagnosis. Two-thirds of the patients had evidence of at least one diabetes related microvascular complication. Conclusion: T2DMY is characterized by a high burden of commonly associated risk factors for both the disease and its long-term complications.

Background and Objectives: Exercise capacity is reduced in chronic kidney failure (CKF). Intra-dialytic cycling is beneficial, but comorbidity and fatigue can prevent this type of training. Low-frequency electrical muscle stimulation (LF-EMS) of the quadriceps and hamstrings elicits a cardiovascular training stimulus and may be a suitable alternative. The main objectives of this trial were to assess the feasibility and efficacy of intra-dialytic LF-EMS vs. cycling., Design, Setting, Participants, and Measurements: Assessor blind, parallel group, randomized controlled pilot study with sixty-four stable patients on maintenance hemodialysis. Participants were randomized to 10 weeks of 1) intra-dialytic cycling, 2) intra-dialytic LF-EMS, or 3) non-exercise control. Exercise was performed for up to one hour three times per week. Cycling workload was set at 40-60% oxygen uptake (VO2) reserve, and LF-EMS at maximum tolerable intensity. The control group did not complete any intra-dialytic exercise. Feasibility of intra-dialytic LF-EMS and cycling was the primary outcome, assessed by monitoring recruitment, retention and tolerability. At baseline and 10 weeks, secondary outcomes including cardio-respiratory reserve, muscle strength, and cardio-arterial structure and function were assessed., Results: Fifty-one (of 64 randomized) participants completed the study (LF-EMS = 17 [77%], cycling = 16 [80%], control = 18 [82%]). Intra-dialytic LF-EMS and cycling were feasible and well tolerated (9% and 5% intolerance respectively, P = 0.9). At 10-weeks, cardio-respiratory reserve (VO2 peak) (Difference vs. control: LF-EMS +2.0 [95% CI, 0.3 to 3.7] ml.kg-1.min-1, P = 0.02, and cycling +3.0 [95% CI, 1.2 to 4.7] ml.kg-1.min-1, P = 0.001) and leg strength (Difference vs. control: LF-EMS, +94 [95% CI, 35.6 to 152.3] N, P = 0.002 and cycling, +65.1 [95% CI, 6.4 to 123.8] N, P = 0.002) were improved. Arterial structure and function were unaffected., Conclusions: Ten weeks of intra-dialytic LF-EMS or cycling improved cardio-respiratory reserve and muscular strength. For patients who are unable or unwilling to cycle during dialysis, LF-EMS is a feasible alternative., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Obstructive sleep apnea (OSA) is associated with several pathophysiological deficits found in diabetic retinopathy (DR). Hence, it's plausible that OSA could play a role in the pathogenesis of sight-threatening DR (STDR)., Objectives: To assess the relationship between OSA and DR in patients with type 2 diabetes and to assess whether OSA is associated with its progression., Methods: A longitudinal study was conducted in diabetes clinics within two U.K. hospitals. Patients known to have any respiratory disorder (including OSA) were excluded. DR was assessed using two-field 45-degree retinal images for each eye. OSA was assessed using a home-based multichannel cardiorespiratory device., Measurements and Main Results: A total of 230 patients were included. STDR and OSA prevalence rates were 36.1% and 63.9%, respectively. STDR prevalence was higher in patients with OSA than in those without OSA (42.9% vs. 24.1%; P = 0.004). After adjustment for confounders, OSA remained independently associated with STDR (odds ratio, 2.3; 95% confidence interval, 1.1-4.9; P = 0.04). After a median (interquartile range) follow-up of 43.0 (37.0-51.0) months, patients with OSA were more likely than patients without OSA to develop preproliferative/proliferative DR (18.4% vs. 6.1%; P = 0.02). After adjustment for confounders, OSA remained an independent predictor of progression to preproliferative/proliferative DR (odds ratio, 5.2; 95% CI confidence interval, 1.2-23.0; P = 0.03). Patients who received continuous positive airway pressure treatment were significantly less likely to develop preproliferative/proliferative DR., Conclusions: OSA is associated with STDR in patients with type 2 diabetes. OSA is an independent predictor for the progression to preproliferative/proliferative DR. Continuous positive airway pressure treatment was associated with reduction in preproliferative/proliferative DR. Interventional studies are needed to assess the impact of OSA treatment on STDR.

Study Objectives: To assess and compare obstructive sleep apnea (OSA) prevalence in South Asians and White Europeans with type 2 diabetes mellitus (T2DM). Secondary aims included exploring possible causes for observed ethnic differences., Methods: A cross-sectional study of patients with T2DM recruited from secondary care diabetes clinics. OSA was defined as an apnea-hypopnea index (AHI) ≥ 5 events/h using home-based, multi-channel respiratory monitoring., Results: Two hundred thirty-four patients (105 South Asian and 129 White Europeans) were studied. The prevalence of mild, moderate, and severe OSA in South Asians was 36.2% (n = 38/105), 9.5% (n = 10/105), and 5.7% (n = 6/105) respectively. After adjustment, OSA was associated with a higher body mass index in South Asians. OSA was significantly less common in South Asians compared to White Europeans (51.4% [54/105] versus 75.2% [97/129], P < .001). OSA was also less severe in South Asians compared to White Europeans (median [interquartile range]: AHI 5.1 [1.4-11.5] versus 8.5 [5.0-20.7] events/h, P < .001; time spent with oxygen saturations < 90% 0.5 [0.0-2.9]% versus 4.0 [0.7-14.4]%, P < .001). Logistic regression showed that only obesity measures explained the ethnic differences in OSA., Conclusions: South Asians with T2DM are at considerable risk of OSA. OSA in South Asians was associated with obesity. However, OSA prevalence was lower in South Asians than in White Europeans. Obesity measures accounted for the observed ethnic differences. Examining factors contributing to ethnic differences will be important to inform screening and treatment strategies., (© 2017 American Academy of Sleep Medicine)

Background: Obstructive sleep apnea (OSA) is associated with increased nitrosative stress, endothelial dysfunction, and peripheral neuropathy in patients with type 2 diabetes. We hypothesized that OSA is associated with Poly ADP ribose polymerase (PARP) activation, lower intra-epidermal nerve fiber density (IENFD), and diabetic foot ulceration (DFU)., Methods: A cross-sectional study of adults with type 2 diabetes recruited from a secondary care hospital in the UK. OSA was assessed by multi-channel home-based cardio-respiratory device (Alice PDX, Philips Respironics). DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI). IENFD and % PAR stained nuclei were assessed using immunohistochemistry staining on skin biopsies. DFU was assessed based on MNSI., Results: Skin biopsies and DFU data were available from 52 and 234 patients respectively. OSA was associated with lower IENFD (12.75±1.93 vs. 10.55±1.62 vs. 9.42±1.16 fibers/mm of epidermis for no OSA, mild OSA and moderate to severe OSA respectively, p<0.001). Following adjustment, mild (B=-2.19, p=0.002) and moderate to severe OSA (B=-3.45, p<0.001) were independently associated with IENFD. The apnea hypopnea index (AHI) was associated with IENFD following adjustment (B=-2.45, p<0.001). AHI was associated with percentage of PAR stained nuclei following adjustment (B=13.67, p=0.025). DFU prevalence was greater in patients with OSA (7.1% vs. 28.1% vs. 26.2% for patients with no OSA, mild OSA and moderate to severe OSA respectively, p=0.001). Following adjustment, OSA was associated with DFU (OR 3.34, 95% CI 1.19-9.38, p=0.022)., Conclusions: OSA is associated with lower IENFD, PARP activation and DFU in patients with type 2 diabetes. Our findings suggest that OSA is associated with small fiber neuropathy. PARP activation is a potential mechanisms linking OSA to DPN and endothelial dysfunction in patients with type 2 diabetes. Whether OSA treatment will have a favorable impact on these parameters and DFU requires interventional studies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Obesity and end-stage renal disease (ESRD) are on the increase worldwide. Kidney transplantation is the treatment of choice for ESRD. However, obesity is considered a contraindication for transplantation. We investigated the effect of BMI on mortality in transplanted and patients remaining on the waiting list in the United Kingdom. We analyzed the UK Renal Registry (RR) and the National Health Service Blood and Transplant (NHSBT) Organ Donation and Transplantation data for patients listed from January 1, 2004 to December 31, 2010, with follow-up until December 31, 2011. Seventeen thousand six hundred eighty-one patients were listed during the study period, with BMI recorded for 13 526 (77%). One- and five-year patient survival was significantly better in all BMI bands (<18.5, 18.5-<25, 25-<30, 30-<35, 35-<40, and 40+kg/m(2) ) in the transplant group when compared to those who remained on the waiting list (p < 0.0001). The analyses were repeated excluding live donor transplants and the results were essentially the same. On analyses of patient survival with BMI as a continuous variable or using 5 kg weight bands, there was no cut-off observed in the higher BMI patients where there would be no benefit to transplantation. For transplanted patients (N = 8088), there was no difference in patient or graft survival between the defined BMI bands. Thus, irrespective of BMI, patient survival is improved if transplanted., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Aims: To investigate concordance with medication, as assessed at baseline and at 1- and 2-year follow-up, and to examine factors associated with non-concordance in a UK-resident South-Asian population., Methods: Data from the UK Asian Diabetes Study were analysed. Concordance with medications was assessed and recorded at three time points during the study. Multiple logistic regression was used to investigate the factors associated with non-concordance; the associations of baseline factors with year 1 concordance and baseline plus year 1 factors with year 2 concordance., Results: Data for 403 patients from seven practices participating in the UK Asian Diabetes Study were analysed. The numbers of patients who were non-concordant were: 63 (16%) at baseline; 101 (25%) at year 1; and 122 (30%) at year 2. The baseline-measured variables that were significantly associated with year 1 non-concordance included diabetes duration, history of cardiovascular disease, components of the EuroQol quality of life questionnaire, the EQ-5D score, and number of medications prescribed. In multivariable analyses, the most important determinant of year 1 non-concordance was baseline non-concordance: odds ratio 13.6 (95% confidence limits 4.7, 39.9). Number of medications prescribed for blood pressure control was also significant: odds ratio 1.8 (95% confidence limits 1.4, 2.4). Similar results were observed for year 2 non-concordance., Conclusions: Non-concordance with medications was common and more likely in people prescribed more medications. The current target-driven management of risk factor levels may lead to increasing numbers and doses of medications. Considering the high cost of medications and the implications of poor health behaviours on morbidity and mortality, further investigation of prescribing behaviours and the factors affecting patient concordance are required., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Objective: Elevated polyclonal serum immunoglobulin free light chains (FLCs; combined FLCκ+FLCλ [cFLC]) are associated with adverse clinical outcomes and increased mortality; we investigated cFLC and cardiovascular disease (CVD) events in type 2 diabetes., Research Design and Methods: In a cohort study of 352 south Asian patients with type 2 diabetes, serum cFLC, high-sensitivity C-reactive protein (hsCRP), and standard biochemistry were measured. CVD events over 2 years were recorded and assessed using multiple logistic regression., Results: cFLC levels were elevated significantly in 29 of 352 (8%) patients with CVD events during 2 years of follow-up (50.7 vs. 42.8 mg/L; P = 0.004). In multivariate analysis, elevated cFLC (>57.2 mg/L) was associated with CVD outcomes (odds ratio 3.3 [95% CI 1.3-8.2]; P = 0.012) and remained significant after adjusting for age, albumin-to-creatinine ratio, diabetes duration, or treatment., Conclusions: cFLC elevation is a novel marker for CVD outcomes in type 2 diabetes that warrants further investigation., (© 2014 by the American Diabetes Association.)

Attendance at diabetic retinopathy screening in minority ethnic groups, including the South Asian population, is known to be poor. We describe a cluster randomised controlled trial conducted in 10 general practitioner (GP) surgeries in Coventry, UK, during 2007 which aimed to evaluate the use of a Link Worker-delivered intervention to improve attendance. The intervention consisted of a simple telephone reminder with the main outcome measure being attendance at diabetic retinopathy screening. We found a statistically significant difference between mean attendance proportions for intervention (0.89) and control (0.74) practices: difference (95% confidence interval (CI)) 0.15 (0.04-0.27), t = 3.03, p = 0.0162; this difference remained significant when adjusted for previous year's proportions. In this proof-of-concept study, in inner city Coventry, we demonstrated increased attendance at diabetic retinopathy screening by use of a simple Link Worker-implemented telephone call intervention. The use of Link Worker phone calls may be a useful tool to increase attendance for diabetic retinopathy screening in a group with high did-not-attend (DNA) rates and a high prevalence of diabetic retinopathy and visual impairment., (© The Author(s) 2014.)

Background: The objective of this study was to investigate the association between ethnicity and health related quality of life (HRQoL) in patients with type 2 diabetes., Methods: The EuroQol EQ-5D measure was administered to 1,978 patients with type 2 diabetes in the UK Asian Diabetes Study (UKADS): 1,486 of south Asian origin (Indian, Pakistani, Bangladeshi or other south Asian) and 492 of white European origin. Multivariate regression using ordinary least square (OLS), Tobit, fractional logit and Censored Least Absolutes Deviations estimators was used to estimate the impact of ethnicity on both visual analogue scale (VAS) and utility scores for the EuroQol EQ-5D., Results: Mean EQ-5D VAS and utility scores were lower among south Asians with diabetes compared to the white European population; the unadjusted effect on the mean EQ-5D VAS score was -7.82 (Standard error [SE] = 1.06, p < 0.01) and on the EQ-5D utility score was -0.06 (SE = 0.02, p < 0.01) (OLS estimator). After controlling for socio-demographic and clinical confounders, the adjusted effect on the EQ-5D VAS score was -9.35 (SE = 2.46, p < 0.01) and on the EQ-5D utility score was 0.06 (SE = 0.04), although the latter was not statistically significant., Conclusions: There was a large and statistically significant association between south Asian ethnicity and lower EQ-5D VAS scores. In contrast, there was no significant difference in EQ-5D utility scores between the south Asian and white European sub-groups. Further research is needed to explain the differences in effects on subjective EQ-5D VAS scores and population-weighted EQ-5D utility scores in this context.

Aims/hypothesis: The aim of this work was to assess the impact of cardiac autonomic neuropathy (CAN) on the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes., Methods: We conducted a cohort study in adults with type 2 diabetes. Patients with end-stage renal disease were excluded. CKD was defined as the presence of albuminuria (albumin/creatinine ratio GFR > 3.4 mg/mmol) or an estimated (eGFR) < 60 ml min(-1) 1.73 m(-2). CKD progression was based on repeated eGFR measurements and/or the development of albuminuria. CAN was assessed using heart rate variability., Results: Two hundred and four patients were included in the analysis. At baseline, the prevalence of CKD and CAN was 40% and 42%, respectively. Patients with CAN had lower eGFR and higher prevalence of albuminuria and CKD. Spectral analysis variables were independently associated with eGFR, albuminuria and CKD at baseline. After a follow-up of 2.5 years, eGFR declined to a greater extent in patients with CAN than in those without CAN (-9.0 ± 17.8% vs -3.3 ± 10.3%, p = 0.009). After adjustment for baseline eGFR and baseline differences, CAN remained an independent predictor of eGFR decline over the follow-up period (β = -3.5, p = 0.03). Spectral analysis variables were also independent predictors of eGFR decline., Conclusions/interpretation: CAN was independently associated with CKD, albuminuria and eGFR in patients with type 2 diabetes. In addition, CAN was an independent predictor of the decline in eGFR over the follow-up period. CAN could be used to identify patients with type 2 diabetes who are at increased risk of rapid decline in eGFR, so that preventative therapies might be intensified.

Objective: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease (ESRD). Obstructive sleep apnea (OSA) is common in type 2 diabetes and increases oxidative stress. Hence, OSA could promote the development and progression of DN., Research Design and Methods: This was a cohort study in adults with type 2 diabetes. Patients with known OSA or ESRD were excluded. DN was defined as the presence of albuminuria or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. DN progression was based on eGFR measurements. OSA was defined as apnea hypopnea index (AHI) ≥5 events/h. Serum nitrotyrosine abundance (a marker of nitrosative stress) was measured by ELISA., Results: A total of 224 patients were included. OSA and DN prevalence was 64.3 and 40.2, respectively. DN prevalence was higher in patients with OSA (OSA+) compared with those without OSA (OSA-) (49.3% vs. 23.8%, P < 0.001). After adjustment, OSA (odds ratio 2.64 [95% CI 1.13-6.16], P = 0.02) remained independently associated with DN. After an average follow-up of 2.5 (0.7) years, eGFR decline was greater in OSA+ compared with OSA- patients (median -6.8% [interquartile range -16.1 to 2.2] vs. -1.6% [-7.7 to 5.3%], P = 0.002). After adjusting, both baseline OSA (B = -3.8, P = 0.044) and AHI (B = -4.6, P = 0.02) remained independent predictors of study-end eGFR. Baseline serum nitrotyrosine abundance (B = -0.24, P = 0.015) was an independent predictor of study-end eGFR after adjustment., Conclusions: OSA is independently associated with DN in type 2 diabetes. eGFR declined faster in patients with OSA. Nitrosative stress may provide a pathogenetic link between OSA and DN. Interventional studies assessing the impact of OSA treatment on DN are needed.

Objective: This study investigated and compared the prevalence of microalbuminuria and overt proteinuria and their determinants in a cohort of UK resident patients of white European or south Asian ethnicity with type 2 diabetes mellitus., Research Design and Methods: A total of 1978 patients, comprising 1486 of south Asian and 492 of white European ethnicity, in 25 general practices in Coventry and Birmingham inner city areas in England were studied in a cross-sectional study. Demographic and risk factor data were collected and presence of microalbuminuria and overt proteinuria assessed., Trial Registration Number: ISRCTN 38297969., Main Outcome Measures: Prevalences of microalbuminuria and overt proteinuria., Results: Urinary albumin:creatinine measurements were available for 1852 (94%) patients. The south Asian group had a lower prevalence of microalbuminuria, 19% vs. 23% and a higher prevalence of overt proteinuria, 8% vs. 3%, χ(2) = 15.85, 2df, P = 0.0004. In multiple logistic regression models, adjusted for confounding factors, significantly increased risk for the south Asian vs. white European patients for overt proteinuria was shown; OR (95% CI) 2.17 (1.05, 4.49), P = 0.0365. For microalbuminuria, an interaction effect for ethnicity and duration of diabetes suggested that risk for south Asian patients was lower in early years following diagnosis; OR for SA vs. WH at durations 0 and 1 year were 0.56 (0.37, 0.86) and 0.59 (0.39, 0.89) respectively. After 20 years' duration, OR = 1.40 (0.63, 3.08)., Limitations: Comparability of ethnicity defined groups; statistical methods controlled for differences between groups, but residual confounding may remain. Analyses are based on a single measure of albumin:creatinine ratio., Conclusions: There were significant differences between ethnicity groups in risk factor profiles and microalbuminuria and overt proteinuria outcomes. Whilst south Asian patients had no excess risk of microalbuminuria, the risk of overt proteinuria was elevated significantly, which might be explained by faster progression of renal dysfunction in patients of south Asian ethnicity.

Background/aim: People of south Asian origin have an excessive risk of morbidity and mortality from cardiovascular disease. We examined the effect of ethnicity on known risk factors and analysed the risk of cardiovascular events and mortality in UK south Asian and white Europeans patients with type 2 diabetes over a 2 year period., Methods: A total of 1486 south Asian (SA) and 492 white European (WE) subjects with type 2 diabetes were recruited from 25 general practices in Coventry and Birmingham, UK. Baseline data included clinical history, anthropometry and measurements of traditional risk factors - blood pressure, total cholesterol, HbA1c. Multiple linear regression models were used to examine ethnicity differences in individual risk factors. Ten-year cardiovascular risk was estimated using the Framingham and UKPDS equations. All subjects were followed up for 2 years. Cardiovascular events (CVD) and mortality between the two groups were compared., Trial Registration Number: ISRCTN 38297969., Findings: Significant differences were noted in risk profiles between both groups. After adjustment for clustering and confounding a significant ethnicity effect remained only for higher HbA1c (0.50 [0.22 to 0.77]; P = 0.0004) and lower HDL (-0.09 [-0.17 to -0.01]; P = 0.0266). Baseline CVD history was predictive of CVD events during follow-up for SA (P < 0.0001) but not WE (P = 0.189). Mean age at death was 66.8 (11.8) for SA vs. 74.2 (12.1) for WE, a difference of 7.4 years (95% CI 1.0 to 13.7 years), P = 0.023. The adjusted odds ratio of CVD event or death from CVD was greater but not significantly so in SA than in WE (OR 1.4 [0.9 to 2.2])., Limitations: Fewer events in both groups and short period of follow-up are key limitations. Longer follow-up is required to see if the observed differences between the ethnic groups persist., Conclusion: South Asian patients with type 2 diabetes in the UK have a higher cardiovascular risk and present with cardiovascular events at a significantly younger age than white Europeans. Enhanced and ethnicity specific targets and effective treatments are needed if these inequalities are to be reduced.

To examine any potential role for 1,25-dihydroxyvitamin D (1,25(OH)2D) in inflammation associated with chronic kidney disease we measured vitamin D metabolites, markers of inflammation and gene expression in 174 patients with a variety of kidney diseases. Urinary MCP-1 protein and renal macrophage infiltration were each significantly but inversely correlated with serum 1,25(OH)2D levels. Logistic regression analysis with urinary MCP-1 as binary outcome showed that a 10-unit increase in serum 1,25(OH)2D or 25OHD resulted in lower renal inflammation. Analysis of 111 renal biopsies found that renal injury was not associated with a compensatory increase in mRNA for the vitamin D-activating enzyme 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1), its catabolic counterpart 24-hydroxylase, or the vitamin D receptor. There was, however, a significant association between tissue MCP-1 and CYP27B1. Patients with acute renal inflammation had a significant increase in urinary and tissue MCP-1, macrophage infiltration, and macrophage and renal epithelial CYP27B1 expression but significantly lower levels of serum 1,25(OH)2D in comparison to patients with chronic ischemic disease despite similar levels of renal damage. In vitro, 1,25(OH)2D attenuated TNFalpha-induced MCP-1 expression by human proximal tubule cells. Our study indicates that renal inflammation is associated with decreased serum vitamin D metabolites and involves activation of the paracrine/autocrine vitamin D system.

Background: Renal disease is common in the general population and whilst few people progress to end-stage renal failure, mortality is increased. The aim of this study was to examine all-cause mortality risk in relation to chronic kidney disease (CKD) stages defined by estimated glomerular filtration rate (eGFR)., Methods: Data were extracted from a computerized central laboratory system for a defined geographical area over a 3-year study period. The eGFR was calculated using the four-variable Modification of Diet in Renal Disease (MDRD) formula and aligned to the MDRD laboratory. Average annual mortality and relative risk (RR) of all-cause mortality was determined and compared for defined age and CKD bands., Results: 106 366 participants (55.5% female; 85% White, 13% South Asian, 2% Black and others) were eligible and studied, representing 49% of the Coventry adult population. 12 540 (12%) of the sample had some evidence of decreased kidney function, with an eGFR <60 ml/min/1.73 m2. 7611 (7%) participants died and there were significantly elevated risks of mortality with increasing renal dysfunction; RR = 4.0, 8.3, 16.2 and 43.5 for eGFR 45-59, 30-44, 15-29 and <15 ml/min/1.73 m2, respectively. Within age bands, RRs were statistically significantly raised with CKD progression and within CKD stage, RR of death decreased as age increased., Conclusions: CKD prevalence increased with age and absolute and RR of mortality increased with progression of CKD. People aged over 75 years, with mild-to-moderate renal disease, representing 41% of this age group, have no increased RR of mortality. Further study of CKD and mortality, particularly progression over time and with respect to age is needed.

A popular hypothesis for the greater prevalence of type 2 diabetes and cardiovascular disease in UK south Asians is that they have an increased susceptibility of developing insulin resistance in response to certain environmental factors, including obesity and adoption of a sedentary lifestyle. Insulin resistance is postulated as a central feature of the metabolic syndrome, culminating in type 2 diabetes, atherosclerotic vascular disease and CHD; a pathway potentially accelerated by migration/urbanisation. We describe and compare the prevalence of type 2 diabetes, cardiovascular disease and their associated risk factors in UK south Asian and white Caucasian populations to determine possible reasons for the increased preponderance of these diseases in south Asians, and highlight key evidence for optimal risk factor management. Finally, we describe a UK community-based programme that attempts to reduce the morbidity and mortality from type 2 diabetes and cardiovascular disease in south Asians through a new approach to management.

Microalbuminuria is more common in South Asian individuals compared to white Europeans. The aim of this study was to determine the relationship between blood pressure and microalbuminuria in a cohort of patients with type 2 diabetes in these two ethnic groups. These further data were analysed from 552 patients (311 South Asian patients and 241 white Europeans) who had microalbuminuria screening data collected. Prevalence of microalbuminuria was significantly higher in South Asian compared with white European patients (31% versus 20%, p=0.007). Among patients with normal, untreated blood pressure, the proportion who had microalbuminuria was three times higher among South Asian patients compared with the white European group (30.7% versus 10.1%, p=0.049, relative risk = 3.1 [1.0-9.5]). In addition, despite their higher cardiovascular risk, South Asian patients were less likely to be prescribed a statin or antihypertensive drug treatment. In conclusion, thresholds and targets for treatment of cardiovascular risk factors in South Asians may need to be lower than those for white Europeans, and targeted intervention will be required to achieve this.

We have recently shown that permanent neonatal diabetes can be caused by activating mutations in KCNJ11 that encode the Kir6.2 subunit of the beta-cell ATP-sensitive K(+) channel. Some of these patients were diagnosed after 3 months of age and presented with ketoacidosis and marked hyperglycemia, which could have been diagnosed as type 1 diabetes. We hypothesized that KCNJ11 mutations could present clinically as type 1 diabetes. We screened the KCNJ11 gene for mutations in 77 U.K. type 1 diabetic subjects diagnosed under the age of 2 years. One patient was found to be heterozygous for the missense mutation R201C. She had low birth weight, was diagnosed at 5 weeks, and did not have a high risk predisposing HLA genotype. A novel variant, R176C, was identified in one diabetic subject but did not cosegregate with diabetes within the family. In conclusion, we have shown that heterozygous activating mutations in the KCNJ11 gene are a rare cause of clinically defined type 1 diabetes diagnosed before 2 years. Although activating KCNJ11 mutations are rare in patients diagnosed with type 1 diabetes, the identification of a KCNJ11 mutation may have important treatment implications.

The Heartbeat Award (HBA) scheme is a national nutrition labelling scheme that operates throughout England. The aim of this study was to assess whether the implementation of the HBA scheme in the workplace results in an improvement in eating habits at work. A longitudinal survey of employees using a structured questionnaire pre- and post-HBA intervention in six workplaces in Leicestershire, England, was conducted. A qualitative food frequency questionnaire was used to assess dietary behaviour 6 months before the scheme was implemented and 6 months afterwards. Four HBA workplaces (n = 453 employees) were compared with two comparison workplaces (n = 124 employees). The outcome measures for dietary change were consumption of 20 food items, i.e. 16 food-frequency and four food-type items. Changes in pre-intervention data compared with post-intervention data evaluated the impact of the HBA on eating habits. Differences were considered statistically different at the p < 0.05 level. Crude and adjusted odds ratios were used to assess differences in change in dietary behaviour between the intervention and comparison workplaces. The results showed that there was significantly more positive change in intervention workplaces only (i.e. the changes were not detected in the comparison workplaces) for four of the 20 food items tested: increase in consumption of fruit (p = 0.029); reduction in consumption of fried foods (p = 0.044) and sweet puddings (p = 0.042); and change to lower fat milks (p = 0.034). In conclusion, the HBA had a modest impact on dietary intake, resulting in a significant positive change in four out of 20 foods consumed by employees in HBA-holding premises.

Aims/hypothesis: This prospective study examined the epidemiology of Type 1 diabetes in young adults in Europe., Methods: We ascertained incident cases of Type 1 diabetes in the 15 to 29 years (both inclusive) age group throughout Europe over a period of 2 years. Diabetes registries in nine countries, in which incidence rates for Type 1 diabetes in the 0 to 14 age group were available, took part. Incidence rates were estimated per 100000 person years and standardised for sex and age. Cumulative incidences per 1000 from birth to age 30 were estimated. Heterogeneity between centres was tested with a Poisson regression model., Results: A total of 2112 diabetes cases were ascertained in 1996 and 1997, of which 61.4% were considered to be Type 1 diabetes. Completeness of ascertainment varied from 70 to 90%. Standardised incidence varied from 4.8 per 100000 person years to 13.4 per 100000 person years. The male-female ratio was estimated to be one or more, and in the 25 to 29 age group 1.5 or more in all countries. Cumulative incidences for males and females indicate that the former exceeds the latter from age 24. In the two centres with highest childhood incidence, this applied already from 14 years of age., Conclusions/interpretation: The incidence of Type 1 diabetes in adults is lower than in children and the range of incidence is also reduced, with a less than threefold variation in adults, against an eightfold variation in children. There is a male excess in incidence, especially in the age group 25 to 29 years.

Background: The authors investigated the relationship between therapeutic blood transfusion before renal transplantation and rejection rates in cyclosporine- and tacrolimus-treated patients., Methods: In one center, 265 consecutive recipients were studied. Protocol induction was with azathioprine, prednisolone, and cyclosporine or tacrolimus; 37% had biopsy-proven acute rejection in the first 6 months and 46% had received zero to two units of blood before transplantation., Results: Lower risk of rejection was associated with tacrolimus induction (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.29-0.95; P=0.049), prior transfusion of three or more units of blood (OR, 0.54; 95% CI, 0.33-0.90; P=0.024), and older age at transplantation (mean, 44.23 +/- 12.56 [+/- SD] years vs. 38.96 +/- 12.37 years; P=0.001). Multiple logistic regression modeling showed the effect of three or more prior transfusions on acute rejection was as follows: OR, 0.49; 95% CI, 0.29 to 0.83; P=0.008., Conclusions: Induction immunosuppression should take account of the higher risk of rejection in patients coming to transplantation who have previously received zero to two units of blood.

Aims: To estimate the prevalence of blindness and partial sight in the general and diabetic populations and to measure the impact of ethnicity and gender on these rates., Methods: Data on visual impairment in the population to be studied was obtained from the Royal Leicestershire Rutland and Wycliffe Society for the Blind (RLRWSB). Using the validated technique of capture-mark-recapture (CMR), a census day was set and data from four sources collected: hospital admissions data, GP returns, wards, and mass media. Computer cross-linkage to Leicestershire Health Authority data ensured patients were alive and resident in Leicestershire at the census date. Estimates of diabetes, ethnicity and gender prevalence were calculated using the 1991 census., Results: CMR calculations revealed that there was under ascertainment of visual impairment in the RLRWSB data. The CMR calculations with direct age standardization estimate the prevalence of blindness and partial sight in the general and diabetic populations to be 51.8/10 000 (CI 50.6-53.0) and 148.8/10 000 (CI 122.1-175.5), respectively. In the diabetic population there was a higher proportion of visually impaired females than males (P < 0.05), with no overall ethnic differences; however, rates were lower than expected in female Indo-Asians. In the general population there was a higher proportion of visually impaired Indo-Asian people (P < 0.01)., Conclusions: Our study has shown the prevalence of visual impairment in both the general and diabetic populations and has demonstrated both ethnic and gender differences. CMR allows the calculation of prevalence of blindness and partial sight from existing data. When comparing the prevalence of visual impairment, whether from diabetes or other causes, it is important to know the gender and ethnicity of the 'at risk' population, as well as the rates in the background population.

Aims/hypothesis: Estimates of incidence of Type I (insulin-dependent) diabetes mellitus in childhood populations vary around the world. This study aimed to estimate and compare the incidence of Type I diabetes in Leicestershire of children of South Asian and White or Other ethnic backgrounds., Methods: All new cases of childhood-onset Type I diabetes diagnosed before 15 years of age in Leicestershire during the period 1989-98 were studied. Population data for Leicestershire from the 1991 census was used. Ethnicity was assigned to all children in the study according to their surnames. Incidence rates (95%-Confidence limits) for the South Asian and white or other ethnic group were estimated and compared., Results: Over the 10-year period, 46 South Asian children and 263 children who were white or from another ethnic group fulfilled the criteria for inclusion in the study. Crude incidence rates per 100,000 person-years were 19.2 (12.0, 29.1) girls and 20.3 (13.0, 30.3) boys for South Asians and 17.7 (14.8, 21.1) girls and 17.7 (14.8, 20.9) boys for whites/others. Age and sex-specific rates were higher for South Asians over 5 years of age but differences were not statistically significant., Conclusion/interpretation: Type I diabetes incidence rates for South Asian children in Leicestershire were very similar to those for children who were in the white/other ethnic group, in contrast to very low rates reported from Asia. The convergence of rates for South Asians with other ethnic groups in Leicestershire suggests that environmental factors are more important than genetic predisposition in causing Type I diabetes in people of South Asian ethnic background.

The Heartbeat Award scheme (HBA) aims to encourage provision and promotion of healthier food choices in catering premises and has been operating in Leicestershire since its launch in England in 1990. This study assessed if the scheme changes dietary attitudes and knowledge of employees in HBA premises. A longitudinal survey of employees in six workplaces was conducted using a structured questionnaire. Employees were investigated before the scheme was implemented and 6 months afterwards. Using a series of validated questions that assessed predisposing and enabling psycho-social factors. Four workplaces with the HBA (N= 453) were compared with two comparison workplaces (N= 124). Nutritional knowledge did not change significantly as a result of the scheme. Employees at HBA workplaces had noticed healthy eating information and acknowledged that it was easier to eat a healthy diet at work after the scheme had been introduced. There was some evidence that the intervention had a maintenance effect in understanding of healthy eating messages, and could act as a buffer to negative external influences. Overall, the scheme was successful in raising awareness of healthy eating in the workplace, but not in enhancing predisposing factors., (Copyright 2000 Academic Press.)

Aims: Use of the oral glucose tolerance test (OGTT) to define glucose intolerance in the general population may bias towards selection of those with insulin resistance. Beta cell function and insulin resistance markers were analysed in four groups: controls (n = 101); fasting hyperglycaemia (FH, n 45); impaired glucose tolerance; (IGT, n = 16) and those with features of both FH and IGT ('Both', n = 30)., Methods: Subjects underwent an OGTT. Plasma glucose, fasting lipid profiles, fasting, 30 and 120 min insulin were measured and beta cell function (% B) and insulin sensitivity (% S) assessed by homeostatic model assessment (HOMA) RESULTS: The FH group compared to controls had a significantly lower % B. The IGT group compared to controls had features of insulin resistance (higher body mass index (BMI), systolic blood pressure and 2 h insulin concentration). Subjects with 'both' IGT and FH had features of insulin resistance (higher BMI, systolic and diastolic blood pressure and triglyceride concentration) as well as beta cell dysfunction with a lower % B and 30 min insulin-glucose ratio compared to controls. There was a preponderance of males in this group. In all, 192 subjects' 30-min insulin concentration and incremental insulin response showed only a significantly negative correlation with fasting glucose concentration. In a linear regression analysis, a low 30-min insulin-glucose ratio was only a significant factor in the fasting glucose model. Thus, higher fasting glucose concentrations appear to be associated with beta cell dysfunction. However, HbA1 only showed a significant correlation with 120-min glucose, not fasting glucose concentration., Conclusions: In those with milder degrees of glucose intolerance, FH is associated with beta cell dysfunction and those with IGT and a relatively 'normal' fasting glucose have features of the insulin resistance syndrome.

Objectives: To investigate the association between multiple sclerosis, dental caries, amalgam fillings, body mercury and lead., Design: Matched case-control study., Setting: Leicestershire in the years 1989-1990., Subjects: Thirty-nine females with multiple sclerosis (of recent onset) were matched with 62 controls for age, sex and general practitioner., Methods: Home interview of cases and controls within which there was an assessment of the DMFT index and blood and urine mercury and lead levels., Results: The odds of being a MS case increased multiplicatively by 1.09 (95% CI 1.00, 1.18) for every additional unit of DMFT index of dental caries. This represents an odds ratio of 1.213 or a 21% increase in risk of MS in relation to dental caries in this population. There was no difference between cases and controls in the number of amalgam fillings or in body mercury or lead levels. There was a significant correlation between body mercury levels and the number of teeth filled with amalgam (controls: r = +0.430, P = 0.006, cases: r = +0.596, P = 0.001)., Conclusion: There was evidence of excess dental caries among MS cases compared with the controls. This finding supports the strong geographical correlation between the two diseases. A further study of this association is recommended.

There is renewed interest in the phase of partial remission in recently diagnosed diabetes because of the potential for pharmacological and immune intervention to preserve beta cell function. 95 children younger than 10 years were investigated to assess the influence of age, sex, diabetic ketoacidosis (DKA), admission at diagnosis, and ethnicity on the frequency of remission and insulin requirements during the first two years after diagnosis. Partial remission was defined as a requirement of insulin < 0.5 U/kg body weight/day. There was partial remission in 41 patients, with no differences for children aged 2-4 years and those aged 5-9 years. None of the five children aged < 2 years remitted. Forty five of 95 children were admitted to hospital at diagnosis, of whom 26 of 45 had DKA (blood pH < 7.25). In this number of children we were unable to show a statistical difference in the rate of remission with respect to DKA, admission to hospital at diagnosis, sex, or South Asian ethnic background. There were no differences in insulin requirements between the different groups by the end of two years and at that time seven of the children required insulin < 0.5 U/kg/day. The results suggest that even in preschool children there is potential for attempting to preserve beta cell function.

The effectiveness of influenza vaccination in reducing hospitalization of people with diabetes for influenza, pneumonia, or diabetic events during influenza epidemics was assessed in a case control study in Leicestershire, England. Cases were 80 patients on the Leicestershire Diabetes Register who were admitted and discharged from hospital with International Classification of Disease codes for pneumonia, bronchitis, influenza, diabetic ketoacidosis, coma and diabetes, without mention of complications, during the influenza epidemics of 1989-90 and 1993. One hundred and sixty-controls, who were not admitted to hospital during this period, were randomly selected from the Register. Immunization against influenza was assessed in 37 cases and 77 controls for whom consent was obtained to access their clinical notes and for whom notes were available. Significant association was detected between reduction in hospitalization and influenza vaccination during the period immediately preceding an epidemic. Multiple logistic regression analysis estimated that influenza vaccination reduced hospital admissions by 79% (95% CI 19-95%) during the two epidemics, after adjustment for potential confounders.

A cross-sectional survey of dietitians using a structured postal questionnaire was sent to 148 dietitians who provided a service to children with diabetes. One hundred and twenty-two (82%) replied, of whom 50 were paediatric dietitians (4 paediatric diabetes dietitians) and 72 were other grades. One hundred and eighteen (97%) dietitians reviewed newly diagnosed children within 24-48 hours of diagnosis but only 81 (66%) used literature specifically designed for children. The majority 116 (95%) felt they worked within a multidisciplinary team. Only 15 (12%) dietitians used purely qualitative carbohydrate dietary education; the remainder used quantitative methods, e.g. 10 g exchange system. Ninety-one (75%) used carbohydrate exchange lists. High fibre foods were suggested but dietitians felt only a moderate intake was achievable. One hundred and twelve (92%) recommended a reduced fat intake but guidance was not as unanimous on reducing specific fatty acids. Objective assessment of dietary outcomes was limited. Paediatric dietitians compared with other grades were more likely to use innovative methods of education but no other differences in dietary practice existed. A minority of dietitians 17 (18%) felt families would find implementing the diet easy. The survey confirmed national inconsistencies in dietary messages and poor evaluation of patient compliance. Research is required into effective dietary counselling to support evidence-based practice.

Study Objective: Analyses of causes of mortality in people with diabetes using data form death certificates mentioning diabetes provide unreliable estimates of mortality. Under-recording of diabetes as a cause on death certificates has been widely reported, ranging from 15-60%. Using a population based register on people with diabetes and linking data from another source is a viable alternative. Data from the Office of Population Censuses and Surveys (OPCS) are the most acceptable mortality data available for such an exercise, as direct comparison with other published mortality rates is then possible., Design: A locally maintained population-based mortality register and all insulin-treated diabetes mellitus cases notified to the Leicestershire diabetes register (n = 4680) were linked using record linkage software developed in-house (Lynx). This software has been extensively used in a maintenance and update cycle designed to maximise accuracy and minimise duplication and false registration on the diabetes register. Deaths identified were initially coded locally to the International Classification of Diseases, 9th revision (ICD9), and later a linkage was performed to use official OPCS coding. Mortality data identified by the linkage was indirectly standardised using population data for Leicestershire for 1991. Standardised mortality ratios (SMR) were estimated, with 95% confidence intervals. Insulin dependent diabetes (IDDM) was defined as diabetes diagnosed before age 30 years with insulin therapy begun within one year of diagnosis. All other types were considered non-insulin dependent diabetes (NIDDM). Analyses were performed for the whole sample and then for the NIDDM subgroup. Results from these analyses were similar and therefore only whole group analyses are presented., Main Results: A total of 370 deaths were identified for the period of 1990-92 inclusive - 56% were in men and 44% in women, median age (range) 71 years (12-94). Approximately 90% of deaths were subjects with NIDDM. Diabetes was mentioned on 215 (58%) death certificates. The all causes SMRs were significantly raised for men and women for all ages less than 75 years. Ischaemic heart disease (ICD9) rubrics 410-414) accounted for 146 (40%) deaths - 41% of male and 38% of female deaths. Male and female SMRs were significantly raised for the age groups 45-64, 65-74, and 75-84 years. Cerebrovascular disease (ICD9 rubrics 430-438) accounted for 39 (10%) deaths and the SMR for women the external causes of death (ICD9 rubrics E800-E999) were also significantly raised overall and in age groups 15-44 and 45-64 years. This was not true for men, although numbers of deaths in this category were small for both men (4) and women (9)., Conclusion: Record linkage has been used successfully to link two local, population based registers. This has enabled an analysis of mortality in people with diabetes to be performed which overcomes the problems associated with using as a sample, death certificates where diabetes is mentioned. The mortality rates and SMRs estimated should more accurately reflect the true rates than would be possible using other methods. The persisting excess mortality identified for people with diabetes is of a similar magnitude and attributable to similar causes as has been reported elsewhere in population based studies.

The relative risk of death by calendar date of diagnosis was investigated in a population-based incident cohort of 845 (463 males:382 females) IDDM diagnosed in Leicestershire before the age of 17 years between 1940 and 1989. The mortality status of 844 (99.9%) patients was determined as of the 31 December 1991, representing 14,346 person-years of risk. Trends in relative risk of death were investigated using Cox proportional hazards modelling for within cohort comparisons and age/sex and calendar time adjusted standardized mortality ratios (SMR) using generalized linear modelling for external comparisons. Median age at diagnosis was 10 years (range 3 months to 16 years); median duration of diabetes 15 years (range 1-51 years). Forty-four patients had died (5.2%; median age at death 31 years, range 11-51 years). A further four patients died at presentation (within 24 h) from ketoacidosis and are excluded from all analyses. Calendar date of diagnosis was found to be an important predictor of mortality. Adjusting for attained age there was evidence of a decline in relative risk of death with calendar date of diagnosis of 3.4% (95% CI, 0.005-6.9%) per annum, equivalent to a 32% fall per decade (95% CI, 5-51%), or 84% (95% CI, 21-97) from 1940 to 1989. The data are consistent with a large fall in mortality between the 1940s and 1950s representing over 50% of the total reduction in mortality between 1940 and 1991. Neither sex nor age at diagnosis were significant predictors of mortality. Over the study period 1940-89 the SMR (male and female combined) fell from 981 (541-1556) to 238 (60-953) relative to the general population. This population-based study shows that the prognosis for Type 1 (insulin-dependent) diabetes mellitus has improved markedly over the period 1940-1991.

Background: The shift in care from secondary to primary services is likely to place greater demands on community hospitals. Before changes in the provision of community hospitals can occur, baseline data are needed, outlining their current use., Aim: A study was undertaken to obtain baseline data describing the use of general practitioner beds in Leicestershire community hospitals., Method: A three-month prospective, observational study was carried out between February and May 1992 using data from a questionnaire completed by nurses and general practitioners and from patient hospital records. Study patients comprised all patients admitted to general practitioner beds in all eight Leicestershire community hospitals., Results: A 100% questionnaire response rate was obtained giving data on 685 hospital admissions. Around 70% of admissions were of patients aged 75 years and over. Of admissions, 35% were for acute care, 31% for respite care, 22% for rehabilitation, 7% for terminal/palliative care and 5% for other reasons. Fifteen per cent of patients had been transferred from a consultant bed. Of those not transferred, 91% were admitted by their usual general practitioner or practice partner and for 96% of these patients this was the general practitioner's first choice for care. There was significant variation in both the age mix and care category mix of patients between individual hospitals. Medical deterioration in an underlying condition and family pressure on the general practitioner or carers' inability to cope each contributed to around half of all admissions. Of all admissions, 38% lived alone, and 18% of carers were disabled. Incontinence was reported for 35% of patients, and 26% of all patients were of a high nursing dependency. There was low utilization of community services before admission and 33% received none. There was variation between individual hospitals in use of local and district general hospital investigations, specialist referral and types of therapy. Of 685 admissions 11% died during their stay. Of those discharged, 76% went to their own or a relative's home, 10% to a residential or nursing home and 9% were transferred to an acute bed. Nine percent of discharges were postponed and 10% were brought forward. On discharge to non-residential care, 26% of patients received no community services., Conclusion: Shifting resources from secondary to primary care is a priority for purchasers. Both the introduction of the National Health Service and community care act 1990, and acute units having increasing incentives for earlier discharge, are likely to place greater demands on community hospital beds. Not all general practitioners have the option of community hospital beds. Before access to general practitioner beds can be broadened, existing beds should be used appropriately and shown to be cost-effective. Purchasers therefore require criteria for the appropriateness of admissions to general practitioner beds, and the results of a general practitioner bed cost-benefit analysis.

During 1990-91 postal questionnaires were sent to the parents of 309 children living in the United Kingdom who developed diabetes before the age of 2 years during 1972-1981. The aim of the survey was to explore how they had coped with their child's condition. Completed questionnaires were returned by 85% of parents. The children had a mean age of 14 (range 9-19) years and diabetes for a mean duration of 13 (range 9-18) years. The cohort's mean age for starting self-injection was reported to be 8 years and most of the children (82%) were still attending full-time education. Diabetes-related difficulties of school were reported for 34% (95% C I 28-40) of the children and 70 (27%, 95% C I 22-32) were estimated to have missed more schooldays than their peers. With increasing duration of diabetes, parents expressed a reduction in anxiety about practical aspects of management such as injections and monitoring, but concern about hypoglycaemia and long-term vascular complications remained high. Parents of girls were more likely to express worries compared to parents of boys, and this excess was significant for worry about diet (chi 2 1df = 17.021, p < 0.001). The paediatric diabetes team caring for early diagnosed children should be aware of the need to discuss the long-term implications of the disorder and be sensitive to the transition period when the child takes progressively more responsibility for self management and the parent's role diminishes.

This study investigated the relationship between the development of diabetic retinopathy and pubertal status at onset of diabetes in 521 Type 1 diabetic patients diagnosed between 1950 and 1985. Pubertal status was based on age at onset (girls > or = 11 years and boys > or = 12 years). Retinopathy (all forms) developed in 112 patients (21.5%; 65 background and 47 proliferative retinopathy). For subjects diagnosed in either the prepubertal or postpubertal period, a similar proportion survived without developing retinopathy for any given duration of diabetes (chi 2 = 0.3822, p = 0.54). However, if only the postpubertal duration of diabetes is considered, then the proportion of patients surviving without retinopathy was significantly less for those diagnosed in the prepubertal period (chi 2 = 14.2, p = 0.002). This study suggests that the prepubertal duration of diabetes is an important phase and that the years prior to puberty do contribute to the risk of developing microvascular injury.

A prevalence study of disability, use of and need for services was undertaken to estimate the need for NHS and other forms of residential, day and respite care for people with severe learning disabilities. Subjects aged 20 or more were drawn from the Leicestershire Learning Disabilities Register (n = 1887). Information was collected by interview with a professional career. The age-specific prevalence was 2.9 per 1000 and the response rate was 88 per cent. A disability rating predicted consultant opinion on need for NHS residential care with a sensitivity and specificity of 82 per cent. Predictive disability factors included problems with behaviour, toileting, speech, epilepsy, postural deformity and use of a wheelchair. Planning targets per 100,000 population aged 20 or more were estimated as follows: NHS residential care--47 places; other residential care--103 places; respite care--36 people; day care--224 places. The need for residential care and medical support remains eminently predictable within the new philosophical framework of provision. Since 1971 the need for NHS residential places has decreased but remains important for people with high dependence. Day care targets have increased and diversified.

Objectives: To document the number of children aged less than 15 years who developed diabetes and were managed within one large health district, and to evaluate the outcome of those children managed without hospital admission at diagnosis., Design: A retrospective study over 1979-88, when a paediatrician and a physician with special interests in childhood diabetes initiated joint clinics. Data collected from the district diabetes register and files of consultants and health visitors specialising in diabetes., Setting: Referral of children to consultants in Leicestershire (total population 863,000)., Main Outcome Measures: The proportion of children managed without hospital admission, comparison of readmission rates and glycated haemoglobin concentrations between children admitted and those not admitted., Results: Over 10 years 236 children aged 10-14 years developed diabetes (annual incidence rate 12.8/100,000 child population (95% confidence interval 11.3 to 14.7)). In total 138 were not admitted to hospital but received supervised management based at home. Admitted children were younger or acidotic or their family doctors did not contact the diabetes team. Duration of admission declined from seven days in 1979-80 to three days in 1987-8. Ninety two were not admitted to hospital during the 10 years for any reason. Significantly fewer children who received management at home were readmitted for reasons related to diabetes than the group treated in hospital (30 (22%) v 40 (41%); p = 0.004). Concentrations of glycated haemoglobin were no different between the two groups., Conclusions: Children with newly diagnosed diabetes may be safely and effectively managed out of hospital. Domiciliary or community based management depends on the commitment of consultants specialising in diabetes working in close cooperation with general practitioners, specialist nurses in diabetes, and dietitians.

Childhood diabetes diagnosed before the age of 24 months presents specific management problems. We report here on the establishment (using the British Diabetic Association [BDA] Children's Register) and mortality of a cohort of children with diabetes diagnosed before age 24 months. Children registered during the period 1972-1981 were traced by contacting consultants or by using the National Health Service Central Registers (NHSCR) of the Office of Population Censuses and Surveys (OPCS). Standardized mortality ratios (SMR) were estimated using person-years of follow-up for each child and age-specific death rates for the England and Wales population for the years 1972-1989. Of 339 children notified during 1972-1981, 231 were traced through consultants and 99 of the remaining 108 through the NHSCR. Twenty were found to be ineligible. The cohort available for mortality analysis comprised 310 (97%) of 319 eligible children. Their age at the time the cohort was established was 8-18 years, and their duration of diabetes 8-17 years. The male:female ratio is 1.4:1. Of 310 children studied, seven have already died: SMR 5.4 (95% CI: 2.5-11.5). We have established a large, unique cohort of children with diabetes diagnosed before age 24 months and still living in the UK and Ireland. The natural history including mortality and occurrence of complications will be analysed prospectively in this cohort and compared to other cohorts of similar disease duration, but later age at onset.