Sire selection and genetic improvement of dairy cattle assuming pure market competition.

Breeding companies and farmers rely on selection indices to identify sires they expect to improve production system profitability. Such indices combine estimates of genetic merit for individual traits with corresponding economic values that are fixed based on circumstances at a particular time. Perfect market competition has also been proposed as an economic basis to value alternative sires. The objective of this study was to propose an economic model and develop it for the evaluation of dairy sires. The pure competition model (PUC) was used to evaluate the relationship between a profitability index based on the PUC approach versus the traditional selection index approach for 330 dairy sires comprising Holstein-Friesians, Jerseys, and Ayrshires. The correlation between these 2 selection indices was only 0.56, indicating that the conventional selection index did not correlate well with an index based on the PUC model. In particular, the higher ranking bulls were overvalued using the conventional selection index. Our study concluded that the use of fixed economic values is problematic for the delivery of consistent rankings in selection indices. In contrast, sire rankings based on PUC are more reliable because the sires are evaluated on the basis of efficiency gains rather than production while accounting for market prices and marginal values of dairy outputs over time.

Protection Against Nephropathy in Diabetes with Atorvastatin (PANDA): a randomized double-blind placebo-controlled trial of high- vs. low-dose atorvastatin(1).

AIMS: To compare the renal effects of low- vs. high-dose atorvastatin in patients with Type 2 diabetes mellitus and optimally managed early renal disease. METHODS: We compared the 2-year progression of nephropathy in a double-blind randomized controlled trial of atorvastatin 80 mg/day (n = 60) vs. 10 mg/day (n = 59) in patients with Type 2 diabetes with microalbuminuria or proteinuria [mean (sd): age 64 years (10 years); HbA(1c) 7.7% (1.3%), 61 mmol/mol (10 mmol/mol); blood pressure 131/73 mmHg; renin-angiotensin system blocker use > 80%; dual blockade > 67%] recruited from diabetes clinics in Greater Manchester. RESULTS: Over (mean) 2.1 years of follow-up, the Modification of Diet in Renal Disease estimated glomerular filtration rate declined by 3 ml min(-1) 1.73 m(-2) in the combined group. The mean (95% CI) between-group difference during follow-up was not significant [2.2 ml min(-1) 1.73 m(-2) (-1.1 to 5.4 ml min(-1) 1.73: m(-2) ), P = 0.20] after adjusting for baseline differences in renal function; positive difference favours 80 mg dose. Similarly, there was no significant difference in creatinine clearance by Cockcroft and Gault [2.5 ml/min (-2.4 to 7.3 ml/min), P = 0.32]; serum creatinine/24-h urine collections [4.0 ml/min (-4.8 to 12.7 ml/min), P = 0.38]; cystatin C (P = 0.69); or 24-h urine protein or albumin excretion (P = 0.92; P = 0.93). We recorded no significant between-group differences in deaths or adverse events. CONCLUSIONS: In patients with Type 2 diabetes with early renal disease, we found no statistical difference in renal function between those taking high- or low-dose atorvastatin over 2 years. We cannot exclude a beneficial effect of < 1.6 ml min(-1) 1.73 m(-2) year(-1) on Modification of Diet in Renal Disease estimated glomerular filtration rate, or if blood pressure management or if renin-angiotensin system blocker use had not been optimized.

Stabilizing effect of exenatide in a patient with C-peptide-negative diabetes mellitus.

BACKGROUND: Exenatide is an incretin mimetic licensed for treatment of Type 2 diabetes poorly controlled despite maximally tolerated doses of oral therapy. Similar in structure to the natural incretin hormone glucagon-like peptide 1 (GLP-1), it helps restore underlying pathophysiological abnormalities. CASE REPORT: We report the successful use of exenatide, combined with insulin, in a 66-year-old woman initially diagnosed with Type 2 diabetes in 1989 but now exhibiting a Type 1 phenotype. Diet, lifestyle advice and oral glucose-lowering agents were commenced but persisting poor control necessitated insulin therapy in 2005. She later presented twice in diabetic ketoacidosis, suggesting conversion to a Type 1 phenotype (postprandial C-peptide < 94 pmol/l). Despite differing insulin regimens, control remained poor with frequent hyperglycaemic and hypoglycaemic excursions, severely impairing quality of life. Whilst an inpatient in 2007 [glycated haemoglobin (HbA(1c)) 10.2%, body mass index (BMI) 31.5 kg/m(2)] exenatide was commenced in an attempt to stabilize glycaemic control. Dramatic improvements were seen and continued. Eight months later, HbA(1c) had fallen by 2% with an 8-kg weight loss and 10-unit reduction in daily insulin dose. Quality of life dramatically improved. C-peptide remains undetectable. CONCLUSIONS: This patient with features of both Type 1 and Type 2 diabetes benefited greatly from exenatide with insulin therapy. The improvement seen in glycaemic control could not be attributable to enhanced insulin secretion but could be as a result of a combination of the other incretin effects (postprandial glucagon suppression, delayed gastric emptying and weight loss secondary to increased satiety) all improving insulin sensitivity, reducing insulin dose and smoothing control.

Interclinician variation in diabetes foot assessment--a national lottery?

AIM: The aim was to evaluate variation among clinicians in the outcome of assessments of foot health status and risk status in patients with diabetes. METHODS: Seventeen clinicians assessed three patients with diabetes using a standardized assessment form and risk classification system. RESULTS: There was variation among clinicians in all aspects of the assessment; recording basic demographic information; taking a medical history; vascular and neurological assessments. Variation was also evident in the risk categories allocated to each of the three patients. CONCLUSIONS: As a consequence of the variation among clinicians in the foot assessment the same patient would have received different care pathways to monitor and manage their foot health depending upon which clinician undertook their initial assessment. We therefore recommend that more attention is placed on training for objective clinical testing, at both pre- and postgraduate levels.

A pilot randomized trial in primary care to investigate and improve knowledge, awareness and self-management among South Asians with diabetes in Manchester.

AIMS: To investigate whether a secondary-primary care partnership education package could improve understanding of diabetes care among South Asians. METHODS: In a pilot randomized controlled trial, in the setting of eight general practices randomized to intervention or control, patients were invited to four or more rotating visits per year by one of a diabetes specialist nurse, dietician or chiropodist working with general practice staff. Participants were from lists of South Asian patients with known Type 2 diabetes in each (general) practice. RESULTS: Patients and practice scores at baseline and 1-year follow-up, from an interview using a questionnaire on knowledge, awareness and self-management of diabetes. Responses were developed into educational packages used during intervention. Of the 411 patients listed at baseline only 211 were traced for interview (refusal only 4%). Mean age was 55.4 years, age of diabetes onset 47.1 years. Fourteen percent were employed and 35% were able to communicate in English fluently. Only 118 could be traced and interviewed at 1 year, although there was no significant difference in demography between those who completed the study and those who did not. Despite a mean of four visits/patient, intervention had no impact on scores for diabetes knowledge, or awareness [score change 0.14, 95% confidence interval (CI) -0.20, 0.49] or self-management (-0.05, 95% CI -0.48, 0.39) between baseline and 1 year. CONCLUSIONS: This form of secondary/primary care support did not transfer information effectively, and we suspect similar problems would arise in other similar communities. Different methods of clinician/patient information exchange need to be developed for diabetes in this South Asian group.

Diabetic ketoacidosis precipitated by thyrotoxicosis.

We report two patients with type 1 diabetes mellitus, previously well controlled with good compliance, presenting with unexplained diabetic ketoacidosis. Following initial correction of the metabolic disorder, persisting tachycardia lead to the diagnosis of thyrotoxicosis. In both cases, treatment with propranolol and carbimazole helped in the stabilization of their metabolic states. Although thyrotoxicosis is known to destabilize diabetes control, we can find no reports of it precipitating diabetic ketoacidosis.

Thyrotoxicosis in old age: a different clinical entity?

Thyrotoxicosis generally presents with classic signs and symptoms in younger people. Among the elderly population atypical presentation is recognized, although this has not been well quantified or characterized. To avoid misdiagnosis or delay in diagnosis, clinical suspicion needs to remain high.

British Diabetic Association guidelines on genetic and immune screening for type 1 diabetes mellitus.

The following article is a report from the Chairman of the Professional Advisory Committee of the British Diabetic Association. The committee, with the help of a number of experts currently working in the field, produced a set of guidelines intended for use by health care professionals on the issues around genetic screening for Type 1 diabetes mellitus. The guidelines were approved by the Board of Management of the British Diabetic Association and we publish them here.

Routine analysis of proteins by Kjeldahl and Dumas methods: review and interlaboratory study using dairy products.

The Kjeldahl and Dumas (combustion) methods were compared in 11 laboratories analyzing samples of milk, skim milk powder, whole milk powder, whey protein concentrate, infant formula, casein, caseinate, 2 reference compounds (glycine and EDTA), and a secondary reference skim milk powder. The comparison was conducted by using international standards where applicable. Overall means were 8.818 g N/100 g by the Kjeldahl method and 8.810 g N/100 g by the Dumas method. No evidence was found for a consistent bias between methods that may be of concern in the trading of dairy produce. A review of more than 10 related trials revealed a lack of consensus in the bias between the 2 methods, suggesting that differences in methodology and sources of systematic error may be contributors. For samples containing > 2 g N/100 g, the Dumas relative repeatability and reproducibility standard deviations were consistently about 0.35 and 0.75%, respectively, whereas the corresponding Kjeldahl values declined generally with N content and were significantly larger. The Dumas precision characteristics may be due to the dominance of Leco analyzers in this trials, and in most other recent trials, rather than an inherent method attribute. Protein determination methods for dairy products need to be reviewed and updated. The Dumas method needs Codex Alimentarius status as a recognized test method.

A comparison of qualitative and quantitative research methods used to assess knowledge of foot care among people with diabetes.

Many diabetes-related pathologies, especially among neuropathic patients, are potentially avoidable. Prevention, however, requires appropriate knowledge and understanding. To assess our ability to effect change in behaviour we need adequate tools to measure not only knowledge but also understanding and change of behaviour. To assess individuals' knowledge and beliefs towards diabetic footcare, we used both quantitative and qualitative methods: a structured questionnaire composed of 20 questions was completed by the respondent, followed by a semi-structured interview conducted by the chiropodist. Results from the structured questionnaire were inconsistent with those from the interviews (Wilcoxon test, p < 0.008). The former demonstrated an average knowledge score of 45% while performance during the interview generated data which suggested poorer knowledge levels. Respondents who correctly identified a series of statements regarding diabetic footcare within the questionnaire could not then apply this knowledge meaningfully when interviewed. A structured questionnaire may not be the best means of assessing patients' knowledge and understanding. We need not only to improve patient education regarding footcare, but also to improve our means of measuring patient knowledge and understanding, more accurately to assess the success or otherwise of our interventions.

Optimal treatment of erectile failure in patients with diabetes.

Erectile failure, although a common problem in male diabetic patients, is one of the most neglected complications of diabetes. The availability of drugs like alprostadil (prostaglandin E1; PGE1) and papaverine for intracavernosal injection and the development of vacuum tumescence devices, while making therapy simple, have also reduced the necessity for specialised investigations. In the past 10 years, alprostadil has been shown to be the safest and the most effective of the intracavernosal self-injection treatments of erectile dysfunction. Vacuum tumescence devices are an acceptable noninvasive alternative in those who fail to achieve a satisfactory response to self-injection. Surgical techniques are being improved every day, and revascularisation procedures and prosthetic implants are available to couples in specialised centres. At present, systemic drug therapy has been largely ineffective for treatment in diabetic patients but progress is being made in this field. Whatever the option, involvement of the partner in decision making is of major importance for the treatment to be successful, and psychosexual counselling is a useful adjunct to medical or surgical therapy.

Cushing's syndrome: still a potential killing disease.

When Harvey Cushing described his syndrome in 1932 he named it the killing disease because of its cardiovascular complications. Heart failure is rarely reported as a presenting feature. We report a case in which left ventricular failure (LVF) was the predominant feature, associated with gross left ventricular hypertrophy (LVH) which regressed after treatment.

Fluoxetine in the treatment of obese type 2 diabetic patients.

In a 12-month randomly allocated double-blind trial in 19 obese Type 2 diabetic patients, fluoxetine 60 mg daily compared to placebo produced a significant fall in median body weight after 3 months (3.8 kg), 6 months (6.5 kg), 9 months (7.1 kg) and at 1 year (5.8 kg). Median fasting blood glucose and HbA1c levels fell significantly after 3 months (1.9 mmol l-1) and 1.7%, respectively) and 6 months (1.8 mmol l-1 and 1.7%) but neither showed a significant difference to placebo after 9 or 12 months therapy with fluoxetine. There were no significant changes in serum cholesterol levels in the year but patients on fluoxetine showed a significant fall in serum triglyceride level (0.5 mmol l-1) after 3 months therapy but not thereafter. Compared to placebo there was a significant fall in median energy intake on fluoxetine after 3 months (257 kcal day-1) and 6 months (199 kcal day-1) but this difference was not significant at 9 or 12 months. There was also a significant fall in carbohydrate intake after 3 months (30 g day-1) and 6 months (23 g day-1) on fluoxetine as well as a significant fall in carbohydrate intake expressed as a percentage of the total daily energy intake; 5.9% at 3 months, 6.1% at 6 months, and 4.0% at 9 months. There were no significant effects on protein or fat intake except a significant increase in the intake of fat expressed as a percentage of daily energy intake, 5.9% after 6 months. Two of the nine patients on fluoxetine dropped out of the study due to gastrointestinal side-effects. Fluoxetine might prove to be a useful adjunct therapy in obese Type 2 diabetic patients where short-term weight loss and fall in carbohydrate intake and an improvement in glycaemia are indicated.

Relapse of maternal thyrotoxicosis presenting as a second-trimester fetal goiter.

A large fetal goiter was detected at 22 weeks of gestation during an antenatal ultrasound scan of a woman with a previous history of Graves' disease treated by partial thyroidectomy. This unsuspected finding initiated maternal investigations and treatment. In untreated cases poor fetal outcome is common and unfortunately fetal thyrotoxicosis/thyroid enlargement frequently remains unrecognized in the first pregnancy. We report the case and its management and discuss the literature emphasizing the importance of screening for antibodies in the 'at-risk' women and the increasing importance of ultrasound in the evaluation and follow-up of these patients. Reports of thyrotoxic fetal goiters are extremely rare and, to our knowledge, there have been no previous reports of this in the second trimester.

The degree of day-to-day variation in food intake in diabetic patients.

A prospective study of food intake using 7 day food diaries was undertaken in 92 diabetic men and women aged 17-81 years. The median individual day-to-day coefficients of variation for energy intake were: in insulin treated patients 12.0%, in non-insulin treated patients 13.7%; for carbohydrate intake 14.5% and 13.8% and for fat 20.7% and 20.8%, respectively. The median individual differences between the minimum and maximum daily intake of energy in insulin treated patients was 787 kcal, in non-insulin treated patients 649 kcal, for carbohydrate intake 89g and 77g and fat 50g and 43g, respectively. Only 39% patients ate within 20% of their prescribed carbohydrate diet. In non-insulin treated patients on prescribed calorie controlled diets, calorie consumption was on average 46% in excess of that prescribed. Although the variation in dietary intake in diabetic patients is large, it is smaller than that reported in non-diabetic subjects in the UK. This variation is likely to make the manipulation of other antidiabetic therapy both difficult and somewhat arbitrary.

Diabetic diets and nutritional recommendations: what happens in real life?

Prospective 7-day estimated weight food records were computer analysed in 92 diabetic patients, 45 men and 47 women, 25 with Type 1 and 67 Type 2 diabetes, attending a hospital-based diabetic clinic. The nutrient intakes were compared with a national survey in non-diabetic British adults (OPCS) and the current EASD recommendations for the diabetic diet. Only three diabetic patients achieved the recommended 50-60% energy intake as carbohydrate, four achieved less than 30% energy as fat, one patient less than 10% saturated fat and 20 ate greater than 30 g fibre per day. The overall nutrient intakes of these diabetic patients reflected those of non-diabetic subjects except for a greater intake of protein and smaller intakes of sugar and alcohol. These findings reinforce the problems currently faced in achieving the present recommendations for the diabetic diet.

Early loss of neurogenic inflammation in the human diabetic foot.

1. Neurogenic inflammation, mediated by nociceptor C fibres, is part of the acute neurovascular response to injury producing the axon reflex flare. Laser Doppler flowmetry was used to measure the flare response induced by the electrophoresis, at various current strengths, of a ring of acetylcholine solution into dorsal foot skin. 2. Nineteen control subjects and 52 long-duration insulin-dependent (Type 1) diabetic patients of similar age (20 without complications; 19 with laser-treated retinopathy; 13 with reduced vibration perception and retinopathy) were studied in order to investigate the possible attenuation of this defence mechanism in diabetes. 3. The maximal (1 mA) flare response [control median (interquartile range): 1.55 (1.16-2.06) arbitrary units] was reduced greatly in neuropathic patients [0.37 (0.24-0.66) arbitrary units; P less than or equal to 0.001 with respect to all other groups], especially those with a previous history of foot ulceration. The flare was also reduced in some patients with retinopathy alone [1.06 (0.56-1.27) arbitrary units; P less than 0.005 with respect to control subjects]. 4. No rightward shift of the curve of hyperaemic response plotted against current strength was found, suggesting that the abnormal response was due to axonal loss rather than to dysfunction. 5. Neurogenic inflammation, mediated by small pain fibres, was markedly impaired in a group of diabetic patients at risk of foot ulceration. Furthermore, impairment of this nociceptor C fibre response can develop before clinical large-fibre neuropathy and could itself predispose to foot complications.