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. METHODS: We analysed a population of predominantly Type 2 diabetic patients, managed in general practice, and screened between 1990 and 2006, with up to 17 years' follow-up and up to 14 screening episodes each. We investigated associations between referable or sight-threatening diabetic retinopathy (STDR), screening interval and frequency of repeated screening, whilst adjusting for age, duration and treatment of diabetes, hypertension treatment and period. RESULTS: Of 63 622 screening episodes among 20 788 people, 16 094 (25%) identified any retinopathy, 3136 (4.9%) identified referable retinopathy and 384 (0.60%) identified STDR. The prevalence of screening-detected STDR decreased by 91%, from 1.7% in 1991-1993 to 0.16% in 2006. The prevalence of referable retinopathy increased from 2.0% in 1991-1993 to 6.7% in 1998-2001, then decreased to 4.7% in 2006. Compared with screening intervals of 12-18 months, screening intervals of 19-24 months were not associated with increased risk of referable retinopathy [adjusted odds ratio 0.93, 94% confidence interval (CI) 0.82-1.05], but screening intervals of more than 24 months were associated with increased risk (odds ratio 1.56, 95% CI 1.41-1.75). Screening intervals of < 12 months were associated with high risks of referable retinopathy and STDR. CONCLUSIONS: Over time the risk of late diagnosis of STDR decreased, possibly attributable to earlier diagnosis of less severe retinopathy, decreasing risk factors and systematic screening. Screening intervals of up to 24 months should be considered for lower risk patients.

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. METHODS: We analysed bed occupancy data for medical or surgical inpatients for 6 years (1998-2004 inclusive), with a DISN service in the final 2 years. Excess bed days per diabetes patient were derived from age band, specialty, and seasonally matched data for all inpatients without diabetes. We also analysed the number of inpatients with known diabetes who did not have diabetes recorded as a discharge diagnosis. RESULTS: There were 14,722 patients with diabetes (9.7% of all inpatients) who accounted for 101 564 occupied bed days (12.4% of total). Of these, 18 161 days (17.8%) were excess compared with matched patients without diabetes, and were concentrated in those < 75 years old. Mean excess bed days per diabetes inpatient under 60 years of age was estimated to be 1.9 days before the DISN appointment, and this was reduced to 1.2 bed days after the appointment (P = 0.03). This is equivalent to 700 bed days saved per year per 1000 inpatients with diabetes under 60 years old, with an identical saving for those aged 61-75 years (P = 0.008), a saving of 1330 diabetes bed days per year by one DISN. Excess diabetes bed occupancy was 167 excess bed days per year per 1000 patients with diabetes in the local population after the DISN appointment. One quarter of the known Type 2 diabetes population were admitted annually, but one quarter of patients had no diagnostic code for diabetes. CONCLUSIONS: Diabetes excess bed occupancy was concentrated in patients < 75 years old, and this was reduced notably following the introduction of a DISN service.

A mobile screening programme for the cardiovascular and microvascular complications of Type 2 diabetes in primary care.

The Diabetes National Service framework (NSF), and the quality payments in the new contract for UK General Practitioners, promote regular screening for diabetes complications. The new contract also includes immediate incentives to meet screening and quality targets, but it will be difficult to meet these targets in primary care. We have developed a mobile 'annual review' programme for patients with Type 2 diabetes managed solely in primary care, that screens for cardiovascular disease, hypertension, retinopathy and neuropathy at the patient's general practice, and gives written foot care, dietary advice and level 1 smoking cessation advice to all patients.

Effect of forage quality on digestion and performance responses of cattle to supplementation with cooked molasses blocks.

We evaluated the effect of forage quality on response of cattle to supplementation with cooked molasses blocks. In Exp. 1, 175 heifers had ad libitum access to prairie hay (5.2% CP, DM basis). Treatments were a 2 x 3 factorial: supplementation with 0 or 1.96 kg/d of alfalfa DM, and supplementation with no cooked molasses block or with a low-protein or a high-protein cooked molasses block (14.4 and 27.5% CP, respectively, DM basis). There were no significant interactions between alfalfa and cooked molasses block for intake or gain. Forage intake and ADG were increased (P < 0.05) by alfalfa supplementation. Heifers fed high-protein cooked molasses blocks gained more (P < 0.05) weight than those fed low-protein cooked molasses blocks or no cooked molasses block. Heifers fed high-protein cooked molasses blocks ate more (P < 0.05) forage than those fed low-protein cooked molasses blocks, with heifers fed no cooked molasses block being intermediate. In Exp. 2, responses to cooked molasses blocks containing 33% CP (DM basis) were measured in 18 steers fed: 1) brome (8.4% CP), 2) alfalfa (19.2% CP), or 3) brome supplemented with 1.93 kg/d of alfalfa DM. Forages were available ad libitum. Forage DM intake was not affected by cooked molasses block and was greater (P < 0.05) for alfalfa than the alfalfa/brome mix, which in turn was greater (P < 0.05) than brome. Digestibility of DM was greater (P < 0.05) for alfalfa than brome or the alfalfa/brome mix and was not affected by cooked molasses block supplementation. Supplementation with cooked molasses blocks had only small effects on intake and digestion of medium- to high-quality forages, but it improved gains and feed efficiencies of heifers fed prairie hay ad libitum, with or without supplemental alfalfa.

Comparison of two reference standards in validating two field mydriatic digital photography as a method of screening for diabetic retinopathy.

AIM: To compare two reference standards when evaluating a method of screening for referable diabetic retinopathy. METHOD: Clinics at Oxford and Norwich Hospitals were used in a two centre prospective study of 239 people with diabetes receiving an ophthalmologist's examination using slit lamp biomicroscopy, seven field 35 mm stereophotography and two field mydriatic digital photography. Patients were selected from those attending clinics when the ophthalmologist and ophthalmic photographer were able to attend. The main outcome measures were the detection of referable diabetic retinopathy as defined by the Gloucestershire adaptation of the European Working Party guidelines. RESULTS: In comparison with seven field stereophotography, the ophthalmologist's examination gave a sensitivity of 87.4% (confidence interval 83.5 to 91.5), a specificity of 94.9% (91.5 to 98.3), and a kappa statistic of 0.80. Two field mydriatic digital photography gave a sensitivity of 80.2% (75.2 to 85.2), specificity of 96.2% (93.2 to 99.2), and a kappa statistic of 0.73. In comparison with the ophthalmologist's examination, two field mydriatic digital photography gave a sensitivity of 82.8% (78.0 to 87.6), specificity of 92.9% (89.6 to 96.2), and a kappa statistic of 0.76. Seven field stereo gave a sensitivity of 96.4% (94.0 to 98.8), a specificity of 82.9% (77.4 to 88.4), and a kappa statistic of 0.80. 15.3% of seven field sets, 1.5% of the two field digital photographs, and none of the ophthalmologist's examinations were ungradeable. CONCLUSION: An ophthalmologist's examination compares favourably with seven field stereophotography, and two field digital photography performs well against both reference standards.

An integrated mobile foot and retinal screening programme for people with Type 2 diabetes managed in primary care.

AIMS: To undertake a vascular and neurological assessment on the feet of all patients with Type 2 diabetes managed solely in local primary care. METHODS: A mobile screening podiatrist (working with an existing mobile retinal screening programme) screened a selected population of 4022 patients with Type 2 diabetes managed solely in 82 general practices. Doppler pressure assessments of peripheral vasculature, bioesthesiometer and monofilament assessment of peripheral neuropathy. RESULTS: This service was administratively simple to set up and integrated well with the retinal screening service and secondary care foot clinic, and was valued by the practices. Disease prevalences were 1.04% for foot ulceration, 19% for peripheral vascular disease and up to 29% for peripheral neuropathy. CONCLUSIONS: This programme screens all patients with known diabetes managed solely in primary care within a district and describes foot morbidity and allows risk stratification. This pattern of service could be a useful template for discussing the diabetes National Service Framework with primary care groups.

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. METHODS: One hundred and seventy-nine pregnancies in 139 women with pregestational Type 1 diabetes were studied prospectively between January 1990 and December 1998. Dilated fundal examination was performed at booking, 24 weeks and 34 weeks or 4-6 weekly if retinopathy present at booking. Data were collected on glycaemic control (HbA(1c)) throughout pregnancy. RESULTS: Progression to proliferative retinopathy was seen in four (2.2%) pregnancies while moderate progression was seen in a further five (2.8%) pregnancies. Progression of retinopathy was significantly increased in women with duration of diabetes 10-19 years compared with duration < 10 years (10% vs. 0%; P = 0.007) and in women with moderate to severe background retinopathy at booking (30% vs. 3.7%; P = 0.01). Although HbA(1c) at booking was higher (7.5% vs. 6.6%; P = 0.08) and the fall in HbA(1c) between booking and 24 weeks was greater (1.6% vs. 1.2%; P = 0.2) in those women showing progression of retinopathy, these changes were not significant. CONCLUSIONS: Progression of retinopathy in pregnancy was uncommon (5.0% pregnancies) but was significantly more common in women with duration of diabetes > 10 years and in women with moderate to severe retinopathy at baseline. Laser therapy was needed in 2.2% pregnancies, which is much lower than that reported in earlier studies. Diabet. Med. 18, 573-577 (2001)

Evaluation of titanium dioxide as a digestibility marker for cattle.

Three studies were conducted to evaluate titanium dioxide (TiO2) as a digestibility marker for cattle. In Exp. 1, eight steers consumed prairie hay ad libitum with or without dietary supplements. Fecal recovery of TiO2 averaged 93% and was not affected (P = 0.47) by supplement. Digestibilities calculated with reference to TiO2 were not different (P = 0.15) from those based on total fecal collections. In Exp. 2, two steers were limit-fed corn-based diets. Fecal recovery of TiO2 averaged 95% and that of chromic oxide (Cr2O3) averaged 113%. Digestibilities calculated with reference to TiO2 were underestimated (P < 0.01) by 1.1 percentage units relative to those based on total fecal collections, and those calculated with reference to Cr2O3 were overestimated (P < 0.01) by 2.0 percentage units. In Exp. 3, eight steers in a replicated 4 x 4 Latin square consumed corn-based diets ad libitum. Fecal recovery of TiO2 averaged 90%, whereas that of Cr2O3 averaged 98%. Digestibilities calculated with reference to TiO2 were underestimated (P < 0.01) by 1.6 to 4.3 percentage units, whereas those calculated with reference to Cr2O3 were not different (P = 0.31) from those based on total fecal collections. Future research is warranted to determine the usefulness of TiO2 in measuring digestibility in cattle.

Effects of L-carnitine on nitrogen retention and blood metabolites of growing steers and performance of finishing steers.

Two experiments were conducted to evaluate L-carnitine supplementation to cattle fed grain-based diets. In Exp. 1, seven Angus-cross steers (216 kg) were used in a 7 x 4 incomplete Latin square experiment to evaluate the effects of supplemental L-carnitine on N balance and blood metabolites. Steers were fed a corn-based diet (17.5% CP) at 2.5% of BW. Treatments were 0, 0.25, 0.5, 1.0, 1.5, 2.0, and 3.0 g/d of supplemental carnitine. The 18-d periods included 13 d for adaptation and 5 d for collection of feces and urine. Blood was collected before feeding and 3 and 6 h after feeding on d 18 of each period. Dry matter intakes tended to be highest when 1.5 g/d of carnitine was supplied, but N retention was not affected by carnitine and averaged 29.3 g/d. Plasma carnitine concentrations and urinary excretion increased with increasing carnitine supply, indicating that at least some of the carnitine escaped ruminal degradation and was absorbed by the steers. Plasma concentrations of NEFA demonstrated a treatment x time interaction; they decreased linearly in response to carnitine before feeding but increased linearly in response to carnitine at 6 h after feeding. Serum insulin and plasma glucagon, IGF-I, cholesterol, triglyceride, and amino acids were not affected by carnitine. Plasma concentrations of glucose, glycerol, urea, and beta-hydroxybutyrate all were increased by some of the levels of carnitine supplementation, but results for these measurements did not follow easily described patterns and seemed to be related to differences in DMI. In Exp. 2, 95 crossbred steers (357 kg initial BW) were fed finishing diets (14.5% CP) for 129 d. Diets were based on steam-flaked corn and contained 6% alfalfa and 4% tallow. Feed intakes, gains, and feed efficiencies were not affected by supplementation with 2 g/d L-carnitine. However, steers receiving L-carnitine tended to have fatter carcasses, as indicated by tendencies (P < 0.2) for thicker backfat, higher marbling scores, and higher yield grades. In conclusion, carnitine supplementation did not alter lean deposition in growing steers but it did alter plasma NEFA concentrations of growing steers fed a corn-based diet and also seemed to increase fat deposition in finishing cattle.

Limiting amino acids for growing Holstein steers limit-fed soybean hull-based diets.

Studies were conducted to determine limiting amino acids (AA) for cattle limit-fed soybean hull-based diets. Ruminally cannulated Holstein steers were maintained in metabolism crates, fed the same basal diet (73% soyhulls, 19% alfalfa, DM basis), and given the same intraruminal infusions (400 g/d acetate; to supply energy without increasing microbial protein supply). Treatments were infused abomasally. In Exp. 1, steers (200 kg) were provided 1) water, 2) 10 g/d of methionine (MET), or 3) a mixture of 10 essential AA (10AA). Nitrogen retention (13.7 g/d) was greatest (P < .05) for steers receiving 10AA. Steers receiving MET (7.9 g/d) had greater (P < .05) N retention than control steers (5.4 g/d). In Exp. 2, steers (200 kg) were provided 10AA or 10AA with L-Lys deleted from the mixture. Steers receiving 10AA tended (P < .09) to have greater N retention (19.0 g/d) than those receiving no lysine (16.3 g/d). In Exp. 3, steers (194 kg) were provided 10AA or 10AA with L-Thr deleted from the mixture. Nitrogen retention was not affected by removal of threonine. In Exp. 4, steers (152 kg) were provided 10AA or 10AA with L-His, L-Trp, L-Arg, L-Phe, or branched-chain AA (L-Leu, L-Ile, and L-Val) removed. Nitrogen retention was reduced (P < .05) by removal of either L-His or the branched-chain AA. For steers limit-fed soybean hull-based diets, methionine was first-limiting; histidine, at least one of the branched-chain AA, and possibly lysine were also limiting.

Prevalence of HFE (hemochromatosis gene) mutations in unselected male patients with type 2 diabetes.

To assess the prevalence of mutations in the HFE (hemochromatosis) gene in unselected male patients with type 2 diabetes, we examined 220 white men without known diabetes and 220 age-matched white men with type 2 diabetes for mutations in the HFE gene. Nucleotide 845 (C282Y) and 187(H63D) alleles were amplified by polymerase chain reaction (PCR) with lymphocyte DNA. The PCR products were analyzed by restriction enzyme digestion. One of the 220 patients (0.45%) with diabetes was homozygous for the HFE 845A (C282Y) mutation and 25 (11.3%) were heterozygous for the same mutation, of whom 3 (1.3%) were compound heterozygotes also carrying the HFE 187G (H63D) mutation. These frequencies did not differ significantly from the control population without diabetes. There is no evidence that HFE mutations are found in excess in unselected male patients with type 2 diabetes, and there is no indication for a population-based search for an excess of these alleles in type 2 diabetes.

Effects of base ingredient in cooked molasses blocks on intake and digestion of prairie hay by beef steers.

Twelve steers (332 kg) were used in three simultaneous 4 x 3 incomplete Latin squares to evaluate effects of beet molasses (BEET), cane molasses (CANE), or concentrated separator by-product (CSB) as base ingredients in cooked molasses blocks on intake and digestion of prairie hay and ruminal characteristics. All steers had ad libitum access to prairie hay (5.9% CP and 69.4% NDF; DM basis). The four experimental treatments included a control (no supplement) and three cooked molasses blocks, based on BEET, CANE, or CSB, fed daily at .125% of BW (.42 kg/d as-fed, .13 kg/d CP). Forage OM, NDF, and N intakes; digestible OM, NDF, and N intakes; and total tract OM and N digestibilities (percentage of intake) were greater (P < .05) for steers fed cooked molasses blocks than for control steers. Total tract OM digestibility was greater (P < or = .06) for steers fed BEET blocks (54.0%) than for those fed CSB (52.1%) or CANE blocks (52.2%). Digestion of NDF was greatest (P < .05) for steers fed BEET blocks (51.9%) and tended to be greater (P < .07) for steers fed CANE (49.3%) or CSB blocks (49.3%) than for control steers (46.9%). Ruminal ammonia concentrations were greater (P < .05) for steers fed cooked molasses blocks (.89 mM) than for control steers (.21 mM); this was primarily due to increases to 4.6 mM at 2 h postfeeding for steers fed blocks. Concentrations of total VFA in ruminal fluid were greater (P < .05) for steers fed BEET (92.7 mM) and CSB (88.1 mM) blocks than for control steers (80.3 mM), whereas concentrations for steers fed CANE blocks were intermediate (85.4 mM). Steers supplemented with cooked molasses blocks had greater molar percentages of butyrate than did control steers, particularly shortly after feeding. In summary, supplementation with cooked molasses blocks increased forage intake and digestion. The three base ingredients elicited similar responses, although steers fed BEET had slightly greater OM and NDF digestibilities than those fed CANE or CSB.

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).

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 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.

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 Steele's 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%. Mari's 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.

A new method of measuring diet abrasion and its effect on the development of the forestomach.

Twelve newborn Holstein bull calves were used to evaluate the effects of dietary abrasiveness, determined by a new method, on ruminal development. Calves were blocked by age and body weight and were assigned to one of three different diets. Each diet had the same ingredients but different particle sizes, which resulted in different abrasive values. No differences were detected in molar percentages of volatile fatty acids in ruminal fluid or in plasma concentrations of urea, glucose, or beta-hydroxybutyrate. The pH of ruminal fluid was lower for calves fed the fine and intermediate diets than for those fed the coarse diet. Digesta-free weights of the stomach and stomach compartments were similar among calves fed the three diets, except that omasum weights were heavier for calves fed the fine diet. Length of the ruminal papillae increased as the abrasive value of the diet decreased. Measurements of ruminal tissue layers from the ventral floor of the cranial sac were not different among diets, but the keratin portion represented more of the epithelial layer for calves fed the diet with the lowest abrasive value, thus decreasing the percentage of metabolically active tissue for those calves.

Using dry feed intake as a percentage of initial body weight as a weaning criterion.

Newborn Holstein heifers (n = 32) and bulls (n = 12) were used to investigate the use of dry feed intake as a percentage of birth weight as a weaning criterion. Three different percentages (1, 1.5, and 2%) were used. Calves in the 1% treatment group met the weaning criterion earlier than did those in the 1.5 and 2% treatment groups; no difference was detected between the latter two groups. Total dry feed intake at 8 wk was higher for calves in the 1% treatment group than for calves in the other treatment groups; no difference was detected between the 1.5 and 2% treatment groups. Weights for all calves at 8 wk and weights of heifer calves at 12, 16, and 20 wk were not different among groups. Using dry feed intake at 1% of birth weight as a weaning criterion reduced days to weaning, increased dry feed intake from birth to 8 wk, decreased variation in weaning age, and had no apparent negative effect on growth at 20 wk of age. Using dry feed intake as a percentage of birth weight appears to be a suitable criterion to determine when to wean dairy calves.

Candidate gene studies in pedigrees with maturity-onset diabetes of the young not linked with glucokinase.

Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterised by an early age of onset and an autosomal dominant mode of inheritance. Only a proportion of cases are due to mutations in the glucokinase gene. We have studied five Caucasian MODY families, including the first MODY family to be described, with five candidate genes implicated in regulation of insulin secretion. The affected subjects showed more marked hyperglycaemia than that found in subjects with glucokinase mutations. We assessed polymorphic markers close to the genes for glucokinase, hexokinase II, adenosine deaminase, pituitary adenylate cyclase-activating polypeptide receptor, and glucagon-like peptide-1 receptor. Linkage analysis with diabetes gave cumulative log of the odds (LOD) scores of less than -3, implying that mutations in these genes are unlikely to provide a major genetic contribution to this form of MODY.