Richard Greenwood

Association between outcome of pregnancy and glycaemic control in early pregnancy in type 1 diabetes: population based study

Recent studies of pregnancy in women in the United Kingdom with type 1 diabetes have shown a fourfold to tenfold increased risk of congenital malformation and a fivefold increased risk of perinatal mortality compared with non-diabetic women. 1 2 These studies used different measures of glycaemic control (concentrations of glycated haemoglobin and fructosamine) both within and between centres so no conclusions were reached about the relation between outcome and glycaemic control. We conducted a population study examining the relation between glycaemic control in early pregnancy and outcome of pregnancy in women with type 1 diabetes. This observational study was carried out in a single centre in Norwich from January 1991 to December 2000. The resident population is 510 000 and mainly white. We defined adverse pregnancy outcome as spontaneous abortion (first or second trimester), major congenital malformation (potentially life threatening …

Grading and disease management in national screening for diabetic retinopathy in England and Wales

Aims  A National Screening Programme for diabetic eye disease in the UK is in development. We propose a grading and early disease management protocol to detect sight‐threatening diabetic retinopathy and any retinopathy, which will allow precise quality assurance at all steps while minimizing false‐positive referral to the hospital eye service.

Impact of pregnancy on the progression of diabetic retinopathy in Type 1 diabetes.

Aims  To evaluate the impact of pregnancy on the progression of diabetic retinopathy in women with Type 1 diabetes mellitus and to identify risk factors for the progression of retinopathy during pregnancy.

Trends in bed occupancy for inpatients with diabetes before and after the introduction of a diabetes inpatient specialist nurse service.

Aims  To compare diabetes bed occupancy and inpatient length of stay, before and after the introduction of a dedicated diabetes inpatient specialist nurse (DISN) service in a large UK Hospital.

Simultaneous time-varying systemic appearance of oral and hepatic glucose in adults monitored with stable isotopes

The rates (and extent) of appearance of glucose in arterialized plasma from an oral glucose load and from liver (RaO, RaH) can be estimated in humans using radioisotopes, but estimates vary among laboratories. We investigated the use of stable isotopes and undertook 22 primed intravenous infusions of D-[6,6-2H2]glucose with an oral load including D-[13C6]glucose in healthy humans. The effective glucose pool volume (VS) had a lower limit of 230 ml/kg body weight (cf. 130 ml/kg commonly assumed). This VS in Steeles one-compartment model of glucose kinetics gave a systemic appearance from a 50-g oral glucose load per 70 kg body weight of 96 +/- 3% of that ingested, which compared with a theoretical value of approximately 95%. Maris two-compartment model gave 100 +/- 3%. The two models gave practically identical RaO and RaH at each point in time and a plateau in the cumulative RaO when absorption was complete. Less than 3% of 13C was recycled to [13C3]glucose, suggesting that recycling errors were practically negligible in this study. Causes of variation among laboratories are identified. We conclude that stable isotopes provide a reliable and safe alternative to radioactive isotopes in these studies.The rates (and extent) of appearance of glucose in arterialized plasma from an oral glucose load and from liver (RaO, RaH) can be estimated in humans using radioisotopes, but estimates vary among laboratories. We investigated the use of stable isotopes and undertook 22 primed intravenous infusions ofd-[6,6-2H2]glucose with an oral load includingd-[13C6]glucose in healthy humans. The effective glucose pool volume (VS) had a lower limit of 230 ml/kg body weight (cf. 130 ml/kg commonly assumed). This VS in Steeles one-compartment model of glucose kinetics gave a systemic appearance from a 50-g oral glucose load per 70 kg body weight of 96 ± 3% of that ingested, which compared with a theoretical value of ∼95%. Maris two-compartment model gave 100 ± 3%. The two models gave practically identical RaO and RaH at each point in time and a plateau in the cumulative RaO when absorption was complete. Less than 3% of13C was recycled to [13C3]glucose, suggesting that recycling errors were practically negligible in this study. Causes of variation among laboratories are identified. We conclude that stable isotopes provide a reliable and safe alternative to radioactive isotopes in these studies.

Incidence and Progression of Diabetic Retinopathy During 17 Years of a Population-Based Screening Program in England

OBJECTIVE To estimate the incidence of diabetic retinopathy in relation to retinopathy grade at first examination and other prognostic characteristics. RESEARCH DESIGN AND METHODS This was a dynamic cohort study of 20,686 people with type 2 diabetes who had annual retinal photography up to 14 times between 1990 and 2006. Cumulative and annual incidence rates were estimated using life tables, and risk factors for progression were identified using Cox regression analysis. RESULTS Of 20,686 patients without proliferative diabetic retinopathy (PDR) or sight-threatening maculopathy at their first retinal examination (baseline), 16,444 (79%) did not have retinopathy, 3,632 (18%) had nonproliferative retinopathy, and 610 (2.9%) had preproliferative retinopathy. After 5 years, few patients without retinopathy at baseline developed preproliferative retinopathy (cumulative incidence 4.0%), sight-threatening maculopathy (0.59%), or PDR (0.68%); after 10 years, the respective cumulative incidences were 16.4, 1.2, and 1.5%. Among those with nonproliferative (background) retinopathy at baseline, after 5 years 23% developed preproliferative retinopathy, 5.2% developed maculopathy, and 6.1% developed PDR; after 10 years, the respective cumulative incidences were 53%, 9.6%, and 11%. Patients with nonproliferative retinopathy at baseline were five times more likely to develop preproliferative, PDR, or maculopathy than those without retinopathy at baseline (adjusted hazard ratio 5.0 [95% CI 4.4–5.6]). CONCLUSIONS Few patients without diabetic retinopathy at the initial screening examination developed preproliferative retinopathy, PDR, or sight-threatening maculopathy after 5–10 years of follow-up. Screening intervals longer than a year may be appropriate for such patients.

Lack of effect of dietary chromium supplementation on glucose tolerance, plasma insulin and lipoprotein levels in patients with type 2 diabetes

Chromium is essential for the regulation of insulin action, thereby influencing carbohydrate and lipid metabolism. An uncontrolled pilot study was designed to measure the habitual daily intake of chromium in a group of healthy individuals with type 2 diabetes and to monitor the effect of daily supplementation with high chromium yeast on glucose tolerance, plasma insulin and lipoproteins. Twelve free-living adults with type 2 diabetes underwent a glucose tolerance test (GTT) on recruitment, at 4 weeks (after a 7-d duplicate diet collection) and at 12 weeks (following 8 weeks daily supplementation with 100 micrograms of chromium). Urine samples were collected on the day before and the day of each GTT. Blood samples were taken at half hourly intervals for 3 hours during the GTT and the plasma glucose, cholesterol, triglyceride, HDL, LDL and insulin concentration measured. The chromium content of diets and urine samples was determined. Fasting glucose concentrations and glucose area under the curve profiles did not alter significantly post supplementation with the chromium rich yeast. No significant changes in insulin and lipoprotein concentrations were observed. The results of this study do not support the hypothesis that individuals with type 2 diabetes benefit from yeast-based chromium supplements (100 micrograms/day).

Trends in yield and effects of screening intervals during 17 years of a large UK community‐based diabetic retinopathy screening programme

Aims  To describe changes in risk profiles and yield in a screening programme and to investigate relationships between retinopathy prevalence, screening interval and risk factors.

A Three‐year Evaluation of the Quality of Diabetes Care in the Norwich Community Care Scheme

The care of patients with diabetes was assessed in eight general practices intending to establish mini‐clinics. Seven of these practices subsequently participated in a mini‐clinic scheme incorporating continuing education and audit. After 3 years further data were collected and compared with the baseline assessment. Seven other local practices which had not set up mini‐clinics were also studied. During the time between the baseline survey and the 3—year assessment the proportion of non‐insulin‐treated patients registered with the mini‐clinic practices and receiving regular review in general practice increased from 54 to 84%. The proportions of patients with a record of body weight, blood pressure, urinary glucose, urinary protein, blood glucose, HbA1, visual acuity, examination of the fundus through dilated pupils, examination of the feet, and a consultation with a dietitian within the previous year increased significantly and were higher in mini‐clinic than in comparison practices although, for a substantial number of patients in both groups of practices, these remained unrecorded. This study shows that organized and audited general practice mini‐clinics can improve the process of care for diabetic patients.

Splanchnic retention of intraduodenal and intrajejunal glucose in healthy adults

Estimates of the spanchnic retention and appearance in the systemic circulation of orally administered glucose vary among laboratories even after recently identified sources of error have been accounted for [Livesey, G., P. D. G. Wilson, J. R. Dainty, J. C. Brown, R. M. Faulks, M. A. Roe, T. A. Newman, J. Eagles, F. A. Mellon, and R. Greenwood. Am. J. Physiol. 275 ( Endocrinol. Metab. 38): E717-E728, 1998]. We questioned whether, in healthy humans,d-glucose delivered intraluminally to the midjejunum appeared systemically as extensively as that delivered intraduodenally. Subjects were infused over a period of 90 min with 50 g of glucose in 1 liter of isotonic saline (incorporating 0.5 gd-[13C6]glucose) per 70 kg of body weight. Infusions were via enteral tubes terminating ∼15 and 100 cm postpylorus. The systemic appearance of glucose was monitored by means of a primed-continuous intravenous infusion ofd-[6,6-2H2]glucose. Whereas 98 ± 2% ( n = 7) of the duodenally infused glucose appeared in the systemic circulation, only 35 ± 9% ( n = 7) of midjejunally infused glucose did so, implying that 65 ± 9% was retained in the splanchnic bed. Either glucose was less efficiently absorbed at the midintestinal site or hepatic glucose sequestration was increased 10-fold, or both. The proximal intestine plays a key role in the delivery of glucose to the systemic circulation, and the distal intestine potentially delivers more glucose to the liver.Estimates of the spanchnic retention and appearance in the systemic circulation of orally administered glucose vary among laboratories even after recently identified sources of error have been accounted for [Livesey, G., P. D. G. Wilson, J. R. Dainty, J. C. Brown, R. M. Faulks, M. A. Roe, T. A. Newman, J. Eagles, F. A. Mellon, and R. Greenwood. Am. J. Physiol. 275 (Endocrinol. Metab. 38): E717-E728, 1998]. We questioned whether, in healthy humans, D-glucose delivered intraluminally to the midjejunum appeared systemically as extensively as that delivered intraduodenally. Subjects were infused over a period of 90 min with 50 g of glucose in 1 liter of isotonic saline (incorporating 0.5 g D-[13C6]glucose) per 70 kg of body weight. Infusions were via enteral tubes terminating approximately 15 and 100 cm postpylorus. The systemic appearance of glucose was monitored by means of a primed-continuous intravenous infusion of D-[6,6-2H2]glucose. Whereas 98 +/- 2% (n = 7) of the duodenally infused glucose appeared in the systemic circulation, only 35 +/- 9% (n = 7) of midjejunally infused glucose did so, implying that 65 +/- 9% was retained in the splanchnic bed. Either glucose was less efficiently absorbed at the midintestinal site or hepatic glucose sequestration was increased 10-fold, or both. The proximal intestine plays a key role in the delivery of glucose to the systemic circulation, and the distal intestine potentially delivers more glucose to the liver.