bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperinsulinaetmia of Hypertriglyceridaemia: A Reappraisal
Authors: Gama R. , Shah S. , Wright J. , Marks V.
Published: July 2009

The peripheral hyperinsulinaemia of hypertriglyceridaemic sbjects has only been defined using insulin immunoassays in which proinsulin and proinsulin fragments cross‐react. Relative contributions of pancreatic secretion and hepatic extraction of insulin to this hyperinsulinaemia have not been studied. We, therefore, reassessed the hyperinsulinaemia of hypertriglyceridaemia by measuring fasting plasma concentrations of intact proinsulin, glucose, insulin, and C‐peptide in 24 hypertriglyceridaemic sbjects with normal glucose tolerance (n = 14) and with impaired glucose intolerance (n = 10) and in normal sbjects (n = 14). Hypertriglyceridaemic sbjects had higher (p < 0.01) fasting concentrations of insulin and C‐peptide and greater (p < 0.01) fasting insulin: C‐peptide molar ratios than in control sbjects. Fasting intact proinsulin concentrations were similar in hypertriglyceridaemic sbjects with normal glucose tolerance and control sbjects but these were lower (p < 0.01) than in hypertriglyceridaemic sbjects with impaired glucose tolerance. These results suggest that the fasting peripheral hyperinsulinaemia of hypertriglyceridaemic sbjects is due to increased pancreatic secretion and reduced hepatic fractional extraction of insulin. The peripheral hyperinsulinaemia of hypertriglyceridaemia appears to reflect peripheral insulin resistance and is not attributable to elevated proinsulin concentrations which are characteristic of impaired glucose tolerance and Type 2 (non‐insulin‐dependent) diabetes mellitus.
Fetal Growth and Glucose and Insulin Metabolism in Four‐year‐old Indian Children
Authors: Yajnik C.S. , Fall C.H.D. , Vaidya U. , Pandit A.N. , Bavdekar A. , Bhat D.S. , Osmond C. , Hales C.N. , Barker D.J.P.
Published: July 2009

Studies in Britain have shown that adults who had a low birthweight have high plasma glucose concentrations 30 and 120 min after an oral glucose load, and an increased risk of Type 2 diabetes and impaired glucose tolerance. Both Type 2 diabetes and low birthweight are common in India. To determine whether low birthweight is associated with reduced glucose tolerance in Indian children, glucose tolerance tests were carried out on 379 4‐year‐old children, whose birthweights were recorded, in Pune, India. Among 201 children who had been looked after on the routine postnatal wards at birth, those with lower birthweights had higher plasma glucose and insulin concentrations 30 min after an oral glucose load, independently of their current size (p = 0.01 and 0.04, respectively). Mean glucose and insulin concentrations were 8.1 mmol I−1 and 321 pmol I−1 in children whose birthweight had been 2.4 kg or less, compared with 7.5 mmol I−1 and 289 pmol I−1 in those who weighed more than 3.0 kg. Among 178 children who had been looked after in the Special Care Baby Unit, those with lower birthweights also had higher plasma insulin concentrations at 30 min but there were no trends with plasma glucose. Our findings suggest that Indian children with reduced intra‐uterine growth have reduced glucose homeostasis after a glucose challenge. This is consistent with the hypothesis that Type 2 diabetes mellitus in India may be programmed in fetal life.
The Insulin‐dependent Patient: Perceptions and Preferences
Authors: Fox C.
Published: July 2009

Although patients realize that insulin is the missing hormone which keeps them alive and well, they do not regard it as a cure for diabetes because it may cause hypoglycaemia, it does not completely abolish the risk of long‐term side‐effects, and it does not permit a life‐style equivalent to their prediabetic state. Clearly, though, insulin can improve quality of life and significantly reduce the risk of complications. Patients' perceptions of their illness and the available treatment have been explored by several means: letters written to a diabetes specialist nurse by children with diabetes, group discussion at a Young Adult Clinic and responses to questions at the annual Youth Diabetes Conference. Improvements in patient care will stem from physicians' awareness of patients' perceptions and from developments in insulin therapy.
Glomerular Charge Selectivity in Type 1 (Insulin‐dependent) Diabetes Mellitus
Authors: Fox J. G. , Quin J. D. , Paterson K. R. , O'Reilly D. StJ. , Smith M. P. , Boulton‐Jones J. M.
Published: July 2009

Glomerular charge selectivity was assessed using the ratio of the clearance of pancreatic isoamylase to the clearance of the more anionic salivary isoamylase (CPAm/CSAm) in 12 normal subjects and 50 patients with Type 1 diabetes: 13 with normal albumin excretion and short duration of diabetes (<5 years), 15 with normal albumin excretion and long duration of diabetes (>15 years), 13 with microalbuminuria, and 9 with clinical nephropathy. None had serum creatinine >200 μmol I−1. There were no significant differences in CPAm/CSAm between the normal subjects and the two groups of normoalbuminuric patients with Type 1 diabetes. CPAm/CSAm was significantly lower in diabetic patients with microalbuminuria or clinical nephropathy than in normoalbuminuric patients with Type 1 diabetes. When the 37 patients with normoalbuminuria and long‐standing diabetes, microalbuminuria, and nephropathy were considered together, there was a significant negative correlation between CPAm/CSAm and albumin excretion rate (rs = 0.71, p < 0.001). Progressive impairment of glomerular charge selectivity at the molecular size of amylase (molecular mass 56 kDa) accompanies increasing albuminuria in Type 1 diabetes.
Epidemiology of Diabetes Mellitus in the Elderly in Northern Greece: a Population Study
Authors: Papazoglou N. , Manes Ch. , Chatzimitrofanous P. , Papadeli E. , Tzounas K. , Scaragas G. , Kontogiannis I. , Alexiades D.
Published: July 2009

This population based study was undertaken to ascertain the overall prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in the elderly using the WHO criteria. The role of obesity in the development of DM or IGT has been investigated for both sexes per decade of age. Furthermore the potential for DM to increase with age, as has been suggested before, has been evaluated using the IGT as a proportion of total glucose intolerance (IGT/TGI) for the same parts of the tested sample. From the 647 persons registered as elderly people in a small town in northern Greece (total population 5875 people), 66 persons did not participate in this survey. Fifty‐six subjects (9.7%) had previously diagnosed DM. The remainder were tested using fasting blood glucose measurements or an oral glucose tolerance test (OGTT). The prevalence of previously undiagnosed DM according to fasting blood glucose values or after 2 h of 75 g load values was 10.1% and 9.3%, respectively. Thus the overall prevalence of DM was 29.1% and of IGT was 15.1%. These data support an increased frequency of DM (65% previously undiagnosed) and IGT in the elderly, whereas this population's susceptibility seems to decline in the older groups for both sexes. Obesity remains a risk factor for DM and IGT particularly among the younger groups although its role has been found to decline with age.
Energy Expenditure in Type 2 Diabetic Patients on Metformin and Sulphonylurea Therapy
Authors: Chong P. K. K. , Jung R. T. , Rennie M. J. , Scrimgeour C. M.
Published: July 2009

Insulin and sulphonylurea therapies have both been reported to cause weight gain in Type 2 diabetic patients whereas metformin does not have this adverse effect. The mechanism for this difference is unclear. We have investigated in a cross‐over study the effect of sulphonylurea and metformin therapy on energy expenditure and body composition in 10 Type 2 diabetic patients (7 females, 3 males) of various weights (mean body mass index 33.4 (SD 7.6 kg m−2)). Free living total energy expenditure was measured over 14 days by the doubly labelled water method adjusted for urinary glucose energy losses and resting energy expenditure by ventilated hood indirect calorimetry. Overall, total energy expenditure (12.88 ± 4.17 vs 13.1 ± 3.69 MJ 24 h−1) and resting metabolic rate (7.30 ± 1.75 vs 7.23 ± 1.74 MJ 24 h−1) were similar on metformin and sulphonylurea therapy, respectively. When adjusted for differences in fat free mass, resting metabolic rate on sulphonylurea therapy was slightly but significantly lower (mean difference −5.5 kJ 24 h−1 kg−1, 95% CI −1.2, −9.9 kJ 24 h−1 kg−1, p < 0.05). Fat free mass also increased significantly by 1.3 kg (95% CI 0.4, 2.4 kg, p < 0.05) when on sulphonylurea therapy, thus compensating for the lower resting metabolic rate per kg fat free mass to leave overall resting metabolic rate unchanged compared to metformin therapy. We also investigated the effect of adding metformin to six Type 2 diabetic patients already on insulin. This did not lead to any measurable changes in any of the components of energy expenditure. Our results suggested that the weight gain of 0.8 kg with sulphonylurea was secondary to a relatively greater energy intake and/or metabolizable energy availability, possibly augmented by a slightly lower resting metabolic rate when adjusted for differences in fat free mass.
The Comparison of Four Weight Reduction Strategies Aimed at Overweight Diabetic Patients
Authors: Manning R. M. , Jung R. T. , Leese G. P. , Newton R. W.
Published: July 2009

Four weight reduction strategies were investigated in a diabetic population who previously had shown little motivation to lose weight. Some 409 patients, body mass index 28–45 were invited to participate. Only 51% replied, although 22 patients (5.4%) lost >3 kg by invitation alone. The study comprised 159 patients, randomly allotted to either regular clinic visits, behavioural group therapy, dexfenfluramine (30 mg d−1 for initial 3 months) or combined home and clinic visits. A further 58 patients were monitored as controls. At 3 months the best weight loss (intention to treat) was achieved using dexfenfluramine with mean weight losses of 1.6, 1.2, 3.4, and 1.7 kg, respectively, in each group. At 1 year weight losses were similar (1.2, 1.8, 2.8, 1.2 kg, respectively) but contrasted with a mean 1.2 kg weight gain in the controls. Some 38% lost >3 kg on dexfenfluramine compared to 19–23% for the others. In those who completed the study, weight loss was similar with behavioural therapy (3 kg) or dexfenfluramine (3.2 kg). We conclude that intensive dietetic efforts can reverse the weight increase in the diabetic population although weight loss is minimal. Dexfenfluramine was most effective in the short term, behavioural therapy useful long term but only in those who remained within the group; home visits offered no advantage.
A Report on the Use of Technician Ophthalmoscopy Combined with the Use of the Canon Non‐mydriatic Camera in Screening for Diabetic Retinopathy in the Community
Authors: Jacob J. , Stead J. , Sykes J. , Taylor D. , Tooke J. E.
Published: July 2009

This paper describes a general practice based diabetic retinopathy screening service employing a technician trained in direct and indirect ophthalmoscopy and taking photographs with a Canon CR3 45 NM non‐mydriatic polaroid camera analysed by a consultant ophthalmologist to provide a comparison with the screener's opinion. Prospective data is presented from the first 1050 patients screened for diabetic retinopathy in the Exeter Health Authority area. Analysis of data collected showed a prevalence of diabetic retinopathy in the screened population of 27 %, 14 % previously undetected with a 0.5 % prevalence of sight‐threatening retinopathy. There was almost complete agreement between ophthalmoscopy findings and the consultant analysis of photographs. Screening costs were calculated at £10.38 per patient screened. A specially trained non‐medically qualified technician can provide a good quality cost‐effective screening service for diabetic retinopathy within a primary care setting.
Educating the Diabetes Care Professionals in Eastern Europe: a Bulgarian Experience
Authors: Christov V. I. , Nestorov I. , Dimitrov A.
Published: July 2009

The first educational course for 30 medical doctors and 16 nurses, engaged in outpatient diabetes care in Bulgaria, was carried out with the aim of assessing the existing level of knowledge of diabetes, to implement a training proramme matching the assessed needs, and to evaluate the efficiency of the education delivered. The initial level of knowledge was assessed by an anonymous pre‐test questionnaire on general issues of diabetes care. After 5 days of training, a post‐test questionnaire was administered which included more specific questions on matters that had been taught during the course. The results of the pre‐test showed that, on average, 60.3 ± 20.6 (SD)% of the doctors and 50.5 ± 25.0% of the nurses gave correct answers. The results of the post‐test were significantly improved (73.5 ± 20.6% for the doctor and 70.8 ± 23.5% for the nurses), although the post‐test questionnaire had been expertly evaluated as more complex and specific. The analysis of the results allowed us to draw general conclusions regarding the educational needs, the optimal structure, and implementation of such training courses in the specific conditions of Bulgaria. Some of the results and conclusions might be useful for other countries from Central and Eastern Europe in their efforts to promote successful diabetes education programmes.
Drugs on the Horizon for Treatment of Type 2 Diabetes
Authors: Rachman J. , Turner R.C.
Published: July 2009

The only new pharmaceutical therapy for Type 2 (non‐insulin‐dependent) diabetes that has become available for clinical use in the last 40 years is the α‐glucosidase inhibitor, acarbose, which reduces postprandial glucose levels by retarding digestion of complex carbohydrates in the gut. It has proved difficult to find other new metabolically active drugs that lack toxicity. Agents that reduce insulin resistance include the thiazolidinediones, which are very effective in animals. Of these, the only one that has been maintained in clinical evaluation appears from preliminary data to have an effect that, although still useful, is not greater than that reported for current oral agents. Agents that reduce nonesterified fatty acid levels by inhibiting lipolysis, thereby allowing increased peripheral uptake of glucose, have so far given minimal reduction in glycaemia. The development of fatty acid oxidation inhibitors to reduce gluconeogenesis in the liver has been hampered by toxicity, but additional new agents are being studied. The most promising new approach for enhancing insulin secretion has been suggested by the demonstration that pharmacological doses of GLP‐1 (7–36 amide), a natural enteric incretin hormone, improves pancreatic β‐cell and α‐cell sensitivity to glucose and can induce normal basal glucose levels in diabetic man. The future development of GLP‐1 agonists will be of great interest. This is timely as other insulin secretogogues, such as α2adrenergic blockers, have proved relatively ineffective. Anti‐obesity agents would in theory be beneficial, but have either had limited efficacy or have been avoided because of concern about long‐term safety. Until new pharmaceutical agents become available, if near‐normal glycaemia is to be achieved, many more Type 2 diabetic patients will need insulin therapy. When full insulin replacement therapy is not feasible, reducing the fasting blood glucose level towards normal with a single daily basal insulin supplement, either alone or in combination with oral agents, could become a more widely used therapy.
Non‐insulin‐dependent Diabetes Mellitus and Islet B‐cell Mitochondrial Glycerophosphate Dehydrogenase Deficiency
Authors: Malaisse W.J.
Published: July 2009

A deficient activity of the mitochondrial FAD‐linked glycerophosphate dehydrogenase (m‐GDH) in the pancreatic islet B‐cell may represent a contributing factor in the pathogenesis of non‐insulin‐dependent (Type 2) diabetes. This enzyme controls circulation in the glycerol phosphate shuttle and, hence, plays a key role in the B‐cell glucose‐sensing device. An impaired activity of this enzyme in pancreatic islets was documented in several, but not all, animal models of inherited or acquired non‐insulin‐dependent diabetes. Enzymatic studies conducted in lymphocytes or islets from diabetic patients, as well as a search for possible mutations of the m‐GDH gene, were recently undertaken to extend these observations to human subjects.
The Relationship Between Pregnancy and Long‐term Maternal Complications in the EURODIAB IDDM Complications Study
Authors: Chaturvedi N. , Stephenson J.M. , Fuller J.H. ,   EURODIAB IDDM Complications Study Group
Published: July 2009

Pregnancy is believed to exacerbate diabetes complications, although the degree to which this occurs, and the advice that should be given to women contemplating pregnancy is unclear. We examined 776 nulliparous and 582 parous women with Type 1 diabetes from a cross‐sectional study performed in 31 European centres. Glycaemic control was better in parous women. Age and duration adjusted prevalence of microalbuminuria was similar in parous and nulliparous women, but macroalbuminuria was lower in parous women (6% versus 10%, p<0.0001). Prevalence of all retinopathy was lower in parous women (34% in women who had two or more pregnancies, 45% in women who had one), compared with 48% in nulliparous women (x2 for trend = 47.1, p<0.0001). Proliferative retinopathy was lower in parous (8% and 7%, respectively) compared with nulliparous women (16%, x2 for trend = 52.2, p<0.0001). These differences persisted when adjusted for glycaemic control. Excluding referrals for pregnancy, parous women were more likely to have been referred to the diabetes clinic with complications than nulliparous women (p=0.001). It is unlikely that our findings can be explained by women with complications being advised against pregnancy, or by the better glycaemic control in parous women. Equivalent levels of microalbuminuria and background retinopathy in parous and nulliparous women suggests that pregnancy may not exacerbate these early complications.
Is There a Seasonal Variation in the Incidence of Gestational Diabetes?
Authors: Moses R. , Griffiths R.
Published: July 2009

It has been suggested that the incidence of gestational diabetes (GDM) may vary with different seasons of the year. The fasting and 2 h glucose levels after a 75 g glucose tolerance test were therefore examined in 2749 women being tested for GDM and were correlated with the mean temperature at 0900 h by month and by season. The mean monthly temperature ranged from 22.3 °C in January to 13.6 °C in July. The monthly incidence of GDM ranged from 3.5 % (95 % Cl, 0.7–6.3) in September to 8.7 % (4.7–12.7) in November. The seasonal incidence of GDM ranged from 7.4 % (5.6–9.2) in autumn to 5.5 % (3.5–7.5) in winter. Chi‐squared analysis did not suggest a significant association between the proportion of women diagnosed with GDM and either the month (p = 0.47) or the season (p = 0.39). Multiple regression analysis, after correction for maternal age, parity, BMI, and the week of testing revealed a non‐significant association between fasting glucose and monthly temperature (p = 0.36) and an increase in the 2 h glucose of 0.026 mmol I−1 for each increase of 1 °C in temperature (p = 0.011). In a temperate coastal area of Australia these differences do not appear clinically significant and have not caused a variation in the incidence of GDM with different seasons.
The Aetiology of Diabetic Neuropathy: the Combined Roles of Metabolic and Vascular Defects
Authors: Stevens M.J. , Feldman E.L. , Greene D.A.
Published: July 2009

A combination of metabolic and vascular defects have been implicated in the pathogenesis of diabetic neuropathy. Animal studies have demonstrated that a reduction in nerve blood flow may be an important early defect and that vasodilators can prevent or ameliorate nerve dysfunction. The potential factors contributing to nerve ischaemia include structural defects in the endoneurial microvasculature together with rheological abnormalities, abnormalities in vasoactive agents which regulate nerve blood flow including nitric oxide and the eicosanoids, and alterations in tone of the autonomic innervation of the nerve vasculature. The principle metabolic defects which have been implicated include disruption of the polyol pathway, altered lipid metabolism, advanced glycosylated end‐product formation, increased oxidative stress, and diabetes‐induced defects in growth factors. The demonstration that activation of the polyol pathway in experimental diabetes may affect nerve blood flow, and conversely that vasoactive agents appear to be important in regulating some aspects of nerve metabolism, has highlighted the interdependence of the metabolic and vascular defects in the pathogenesis of this condition. Thus, selective intervention aimed at a key defect early in this cascade may subsequently correct a number of later abnormalities offering therapeutic hope in this chronic debilitating complication.
The Association of Fibrinolysis and Hyperlipidaemia with Quantitative Sensory Tests in an Epidemiological Study of Swedish Type 1 Diabetic Patients
Authors: Lithner F. , Bergenheim T. , Borssén B. , Dahlén G. , Nilsson T.K.
Published: July 2009

Serum levels of cholesterol, HDL‐cholesterol, triglycerides, lipoprotein Lp(a), and the fibrinolysis factors tPA (tissue plasminogen activator) and PAI‐1 activity (plasminogen activator inhibitor) were compared with sensory thresholds for vibration, electrical current perception, and pain in a population‐based study comprising 239 patients with diabetes mellitus Type 1, aged 15–50 years. Univariate regression analyses (n = 180) showed significant correlations between elevated sensory thresholds and age, duration of diabetes, serum cholesterol and triglycerides, and HbA1c. In multivariate regression analysis, age, duration of diabetes, height, and serum triglycerides showed significant independent associations with five or six of the six measured sensory threshold variables. In addition there was a significant association between increased thresholds for vibration and Lp(a) levels. Thus, increased sensory thresholds for vibration, current perception, and pain in patients with Type 1 diabetes are associated with increased serum triglyceride levels, and Lp(a) levels are associated with increased threshold for vibration. Fibrinolytic activity is unrelated to these measures of nerve function in Type 1 diabetic patients.
Comparison of the Effects on the Diurnal Blood Pressure, Glucose, and Lipid Levels of a Diet Rich in Monounsaturated Fatty Acids With a Diet Rich in Polyunsaturated Fatty Acids in Type 2 Diabetic Subjects
Authors: Thomsen C. , Rasmussen O.W. , Hansen K.W. , Vesterlund M. , Hermansen K.
Published: July 2009

The influence on blood pressure, glucose metabolism, and lipid levels of an exchange of polyunsaturated fatty acids with monounsaturated fatty acids in the diet was compared in 16 Type 2 diabetic outpatients. In a cross‐over study design the patients were randomly assigned to 3 weeks treatments with a diet containing 30% energy as monounsaturated fatty acids, or an isoenergetic diet with 30% energy as polyunsaturated fatty acids. The contents of total fat, satuarated fatty acids, cholesterol, and fibre were similar in the two diets. On the last days of the two diet periods, 24‐h ambulatory blood pressure was measured and the responses of glucose, hormones, and lipids to a carbohydrate rich test meal were measured. As compared with the polyunsaturated fatty acids diet, the monounsaturated fatty acids diet reduced 24‐h systolic (129 ± 11 vs 124 ± 8 mmHg (mean ± SD), p = 0.02) and diastolic blood pressure (76 ± 11 vs 73 ± 8 mmHg, p = 0.02). The two diets had similar, beneficial effects on glycaemic control, and cholesterol and lipoprotein concentrations. A diet rich in monounsaturated fatty acids has beneficial effects on the blood pressure, while similar effects on glucose and lipid levels are observed in normotensive Type 2 diabetic subjects.
Short‐term Mortality in Childhood Onset Insulin‐dependent Diabetes Mellitus: a High Frequency of Unexpected Deaths in Bed
Authors: Sartor G. , Dahlquist G.
Published: July 2009

Mortality and the causes of death have been studied in a population‐based cohort of 4919 childhood onset IDDM cases. Enrolment began in 1977 and at the time of study there had been a maximum duration of disease of 13.5 years, with a total of 33 721 person years at risk. Survival status was ascertained by linkage to the Swedish Cause‐of‐Death register. Death certificates, autopsy protocols, and hospital records were scrutinized for classification of causes of deaths. Twenty males and 13 females with IDDM died before the age of 28.5 years. This corresponds to a Standardized Mortality Rate for age of 262% (95% confidence limits, 172–400) for the boys and 384% (95% confidence limits, 232–635) for girls. Seven patients died of ketoacidosis, four at onset of diabetes. Nine cases were found ‘dead in bed’, having been seen apparently healthy 1–2 days before death. One of these cases had signs of cerebral haemorrhages at autopsy and another one had signs of bite marks in the mouth, but otherwise all autopsies were normal and no evidence of alcohol or other intoxication was found. In a well‐educated population with good access to inexpensive diabetes care, there is still a two‐ to threefold excess mortality among young onset insulin‐dependent diabetic individuals including a high frequency of unexplained deaths in bed.
Frequency of Thyroid Dysfunction in Diabetic Patients: Value of Annual Screening
Authors: Perros P. , McCrimmon R.J. , Shaw G. , Frier B.M.
Published: July 2009

A randomly selected group of 1310 adult diabetic patients attending a diabetic outpatient clinic received annual screening for thyroid disease, by estimating serum free thyroxine and TSH concentrations. The overall prevalence of thyroid disease was found to be 13.4%, and was highest (31.4%) in Type 1 diabetic females, and lowest in Type 2 diabetic males (6.9%). As a direct result of screening, new thyroid disease was diagnosed in 6.8% (89 patients) of the population screened; the commonest diagnosis was subclinical hypothyroidism (4.8%), followed by hypothyroidism (0.9%), hyperthyroidism 0.5%), and subclinical hyperthyroidism (0.5%). Female patients with Type 1 diabetes had the highest annual risk of developing thyroid disease (12.3%), but all patient groups had a higher incidence of thyroid dysfunction, compared to that reported in the general population. This study suggests that thyroid function should be screened annually in diabetic patients to detect asymptomatic thyroid dysfunction which is increased in frequency in a diabetic population.
Microalbuminuria: Prognostic and Therapeutic Implications in Diabetic and Hypertensive Pregnancy
Authors: Bar J. , Hod M. , Erman A. , Friedman S. , Ovadia Y.
Published: July 2009

Microalbuminuria is defined as urinary excretion of albumin that is persistently above normal, although below the sensitivity of conventional semiquantative test strips. Several studies have reported that Type 1 diabetic patients with microalbuminuria are apparently more likely to develop diabetic nephropathy eventually progressing to renal failure. Microalbuminuria is also a strong predictor of mortality in Type 2 diabetes, and is correlated with increased blood pressure in patients with benign essential hypertension. Radioimmunoassay revealed a significantly higher urinary albumin excretion rate in normal pregnant women in the third trimester of pregnancy, compared to the second and first, and compared to non‐pregnant women. Microalbuminuria was found in 30% of women who had a record of gestational diabetes mellitus. Published results are controversial regarding the assumption that microalbuminuria is an early predictor of pregnancy‐induced hypertensive complications.
Decreased Sialidase Activity in Mononuclear Leucocytes of Type 1 Diabetic Subjects: Relationship to Diabetic Complications and Glycaemic Control
Authors: Waters P.J. , Flynn M.D. , Pennock C.A. , Corrall R.J.M. , Greenwood R.J. , Eisenthal R.
Published: July 2009

Leucocyte surface sialic acid content influences surface charge, deformability, and leucocyte‐endothelial interaction. Abnormal leucocyte structure and function contributes both to microvascular damage and diabetic complications. The aim of this study was to investigate altered leucocyte SA metabolism in diabetic subjects and measure lysosomal sialidase which regulates leucocyte surface sialylation. We examined 26 Type 1 (insulin‐dependent) diabetic subjects with retinopathy, 26 Type 1 diabetic subjects without complications, and 38 matched normal control subjects. Sialidase was assayed in freshly prepared sonicates of pure mononuclear leucocytes (MNLs), using the fluorometric substrate 4‐methyl‐umbelliferyl‐N‐acetylneuraminic acid. In the subjects with diabetes there was a significant negative correlation between MNL sialidase activity and both HbA1c (rs = 0.37, p = 0.007) and fructosamine (rs = −0.31, p = 0.026). MNL sialidase activity was significantly decreased in diabetic subjects with clinical evidence of complications compared to control subjects. HbA1c was significantly higher (p = 0.036) in diabetic patients with complications compared to those without. The observed decrease in MNL sialidase activity related to diabetic control may be important in the pathogenesis of vascular damage. Diabetes‐associated changes in sialylation of functional cell surface glycoconjugates may have important clinical consequences.
Thinness at Birth and Glucose Tolerance in Seven‐year‐old Children
Authors: Law C. M. , Gordon G. S. , Shiell A. W. , Barker D. J. P. , Hales C. N.
Published: July 2009

Adults who had low birthweight and were thin at birth have an increased risk of Type 2 diabetes and impaired glucose tolerance. To discover whether thinness at birth is associated with reduced glucose tolerance in children, 250 7‐year‐old children underwent an abbreviated oral glucose tolerance test. Children who were thin at birth, as measured by a low ponderal index (birthweight length‐3) had higher plasma glucose concentrations. Plasma glucose concentration 30 min after a glucose load rose by 0.07 mmol l‐1 (95% confidence interval 0.00 to 0.14; p = 0.04) for every unit (kg m‐3) fall in ponderal index. Children in the lowest quarter of the distribution of ponderal index (23 kg m‐3 or less) had a mean 30 min plasma glucose concentration of 8.49 mmol l‐1 compared to a mean of 7.97 mmol l‐1 for those in the highest quarter (>27.5 kg m‐3). These associations were independent of duration of gestation, gender, social class or the child's current weight. This is consistent with the hypothesis that Type 2 diabetes originates in utero.
Undiagnosed Glucose Intolerance in the Community: the Isle of Ely Diabetes Project
Authors: Williams D. R. R. , Wareham N. J. , Brown D. C. , Byrne C. D. , Clark P. M. S. , Cox B. D. , Cox L. J. , Day N. E. , Hales C. N. , Palmer C. R. , Shackleton J. R. , Wang T. W. M.
Published: July 2009

The Isle of Ely Diabetes Project is a prospective population‐based study of the aetiology and pathogenesis of Type 2 diabetes mellitus. Between 1990 and 1992, 1156 subjects aged between 40 and 65 years underwent a standard 75 g oral glucose tolerance test (OGTT). A total of 1122 individuals who were not known to have diabetes completed the test and were classified according to WHO criteria; 51 subjects (4.5%) had previously undiagnosed diabetes and 188 (16.7%) had impaired glucose tolerance. The subjects with newly diagnosed glucose intolerance were significantly older, more obese, and shorter than those with normal glucose tolerance. Blood pressure, cholesterol, triglyceride, and LDL‐cholesterol concentrations were elevated and HDL‐cholesterol levels were lower among those with abnormal rather than normal glucose tolerance. In multiple regression analyses stratified by gender and including age, body mass index, and the waist‐hip ratio as covariates, there were significant differences between those with normal and abnormal glucose intolerance in blood pressure, triglyceride, and HDL‐cholesterol, but not total or LDL‐cholesterol. In both male and female subjects, height had a significant independent negative association with the plasma glucose at 120 min after administration of oral glucose (standardized β coefficient = ‐0.12, p<0.01).
Night Blood Pressure: Relation to Organ Lesions in Microalbuminuric Type 1 Diabetic Patients
Authors: Hansen K. W. , Sørensen K. , Christensen P. D. , Pedersen E. B. , Christiansen J. S. , Mogensen C. E.
Published: July 2009

Ambulatory blood pressure was measured in 23 microalbuminuric Type 1 diabetic patients without hypertension. Nine patients had a reduction in mean arterial blood (MAP) pressure at night < 10% of their day‐time value (non‐dippers). The following parameters were measured: glomerular filtration rate (GFR), overnight urinary excretion of albumin (UAE), sodium and potassium, left ventricular dimensions, extracellular volume (ECV), plasma aldosterone, and arginine vasopressin (AVP). Night‐time MAP was 11 mmHg lower in patients designated as dippers than in non‐dippers. Day‐time MAP was similar in dippers (98 ± 5 mmHg) and non‐dippers (99 ± 8 mmHg, NS). No statistical significant difference was found for UAE in dippers (geometric mean, x/– tolerance factor, μg min‐1) (72 x/– 2.1) vs non‐dippers (63 x/– 2.1), for left ventricular mass index (63 ± 12 vs 59 ± 10 g m‐2), or for GFR (134 ± 19 vs 148 ± 22 ml min‐1). Aldosterone and AVP were lower in non‐dippers (p < 0.05) and a negative correlation in all patients was noticed between ECV and aldosterone (rho = −0.50, p < 0.05). Sodium and potassium excretion and ECV were indistinguishable between the groups. We conclude (1) that impaired reduction of night blood pressure does not seem to be associated with more signs of renal or cardiac lesions and (2) that the lower aldosterone and AVP in non‐dippers may counteract volume expansion.
‘Hospital Hyperglycaemia’; Perception or Reality?
Authors: Lakshmi M. Vijaya , Tieszen K. L. , Hollis S. , Wong L. , Dornan T. L.
Published: July 2009

Patients' perceptions that clinic fasting blood glucose measurements in Type 2 diabetes are artefactually high were investigated. Eighteen men and 14 women in the Salford cohort of the United Kingdom Prospective Diabetes Study (UKPDS) with a median age of 51 (range 37–69) years measured their fasting blood glucose concentration at home with visually read sticks or meters; they then collected capillary blood into fluoride tubes both at home and in clinic after a median lapse of 77 (range 25–173) min. The clinic samples were measured immediately and after a time lapse equivalent to the time taken to reach clinic to control for continued glycolysis in the home sample. Mean fasting blood glucose was 5.9 ± 1.9 mmol 1‐1 by the patients' own measurement and 6.0 ± 1.8 mmol 1‐1 on the home collected sample compared with 6.2 ± 2.0 mmol 1‐1 and 6.1 ± 2.0 mmol 1‐1 on the hospital immediate and time‐lapsed measurements, respectively (p > 0.05 for all comparisons between home and hospital measurements); although there were no systematic differences, occasional measurements differed more than 2 mmol 1‐1. These data support the use of the fasting blood glucose level as a stable, patient‐independent measure of glycaemic control in Type 2 diabetes
Fetal Growth and Insulin Resistance in Adult Life: Role of Plasma Triglyceride and Non‐esterified Fatty Acids
Authors: Phillips D.I.W. , Osmond C. , McLeish R. , Hales C.N.
Published: July 2009

Reduced fetal growth is associated with insulin resistance and a high prevalence of glucose intolerance in adult life. Because babies who are growth retarded have elevated levels of triglyceride and non‐esterified fatty acids (NEFA), and because similar abnormalities are observed in subjects with the insulin resistance syndrome, impaired regulation of lipid metabolism could be one of the mechanisms explaining the link between reduced fetal growth and insulin resistance. We have, therefore, measured fasting plasma triglyceride and NEFA, and the insulin‐mediated suppression of NEFA during an oral glucose tolerance test in 93 men and women aged 50, born in Preston, whose birthweight and body size at birth had been recorded. Elevated fasting plasma triglycerides and reduced NEFA suppression during the oral glucose tolerance test were associated with the male sex, glucose intolerance, central obesity as indicated by a high waist to hip ratio and insulin resistance as measured by a short insulin tolerance test. However there were no statistically significant relationships between the birth measurements and the circulating lipid levels. Moreover in regression analyses the relationships between thinness at birth and insulin resistance or glucose intolerance in adult life were unaffectived by the addition of triglyceride or NEFA in the models. These results suggest that the link between reduced fetal growth and insulin resistance in the adult is not mediated by an abnormal regulation of lipid metabolism.
Reduced Plasma Aldosterone Concentrations in Randomly Selected Patients with Insulin‐dependent Diabetes Mellitus
Authors: Cronin C.C. , Crowley B. , Ferriss J.B. , Barry D.
Published: July 2009

Abnormalities of the renin‐angiotensin system have been reported in patients with diabetes mellitus and with diabetic complications. In this study, plasma concentrations of prorenin, renin, and aldosterone were measured in a stratified random sample of 110 insulin‐dependent (Type 1) diabetic patients attending our outpatient clinic. Fifty‐four age‐ and sex‐matched control subjects were also examined. Plasma prorenin concentration was higher in patients without complications than in control subjects when upright (geometric mean (95 % confidence intervals (CI): 75.9 (55.0–105.6) vs 45.1 (31.6–64.3) mU I‐1, p < 0.05). There was no difference in plasma prorenin concentration between patients without and with microalbuminuria and between patients without and with background retinopathy. Plasma renin concentration, both when supine and upright, was similar in control subjects, in patients without complications, and in patients with varying degrees of diabetic microangiopathy. Plasma aldosterone was suppressed in patients without complications in comparison to control subjects (74 (58–95) vs 167 (140–199) ng I‐1, p < 0.001) and was also suppressed in patients with microvascular disease. Plasma potassium was significantly higher in patients than in control subjects (mean ± standard deviation: 4.10±0.36 vs 3.89±0.26 mmol I‐1; p < 0.001) and plasma sodium was significantly lower (138 ± 4 vs 140 ± 2 mmol I‐1; p < 0.001). We conclude that plasma prorenin is not a useful early marker for diabetic microvascular disease. Despite apparently normal plasma renin concentrations, plasma aldosterone is suppressed in insulin‐dependent diabetic patients.
Differences in Preferences Between Diabetic Patients and Diabetologists Regarding Quality of Care: a Matter of Continuity and Efficiency of Care?
Authors: Casparie A.F. , van, der Waal M.A.E.
Published: July 2009

Diabetologists and diabetic patients were asked about their preferences for aspects of care which are considered of importance in relation to the quality of care. A questionnaire was constructed using the method of pairwise comparison in which respondents constantly had to chose between three statements in order to get a priority list. Adults with diabetes mellitus (Types 1 and 2) attending outpatient departments were asked to fill in the questionnaire. A response rate of 97 % was recorded (n = 94). Diabetologists received a postal questionnaire and the response rate was 65 % (n = 126). There was a reasonable agreement between both populations and ‘effectiveness of care’ was ranked the highest. However, the patients gave a significant higher ranking to ‘continuity of care’ and a lower ranking to ‘efficiency’. Neither the age and sex of the patients nor the duration of the disease had any influence on their opinions. Patients who were treated with oral medication ranked ‘information’ higher than patients using insulin, but the difference was not significant. A lower level of education and having public‐health insurance were associated with a higher preference for ‘continuity’. No differences were found regarding age and sex within the diabetologist population.
BOOK REVIEW
Authors: Ewins D.L.
Published: July 2009

Book reviewed in this article:

Chronic Complications of Diabetes edited by John C. Pickup and Gareth Williams
Beyond the Distinction between Positivism and Non‐Positivism*
Authors: PERRY STEPHEN
Published: July 2009

In this article I discuss a number of issues raised by Professor Jules Coleman's recent article “Beyond the Separability Thesis.” I suggest, to begin, that Coleman is correct that neither a narrow nor a broad formulation of the separability thesis takes us very far towards a robust distinction between legal positivism and legal non‐positivism. I then offer a brief discussion of methodology in jurisprudence, suggesting that Coleman accepts, at least implicitly, what I call a “methodology of necessary features.” Since there is reason to think that law possesses some necessary features that are non‐normative (or descriptive) and others that are moral in character, the promise of this pluralistic approach is that it will be capable of bridging the gap between so‐called “descriptive” and “normative” theories of methodology in jurisprudence. Since the distinction between descriptive and normative methodological theories is sometimes taken to be one way, among others, of drawing a distinction between positivist and non‐positivist theories of law, the pluralism of the “methodology of necessary features” gives us yet one more reason to think that the distinction between positivism and non‐positivism is not a theoretically fundamental one. Finally, I discuss Coleman's “moral semantics claim,” i.e., the idea that “legal content is best understood as moral directives about what is to be done and who is to decide what is to be done.” Coleman acknowledges that the moral semantics claim, when taken together with the social facts thesis, raises a well‐known problem: How can social facts create content‐independent reasons for action? I suggest that we are most likely to find the answer to this question by focusing directly on whether or not law's claimed moral authority—meaning its claimed moral power—can be justified, rather than by focusing indirectly, as many theorists have done, on the existence or non‐existence of a general obligation to obey the law.
Was Inclusive Legal Positivism Founded on a Mistake?
Authors: SHAPIRO SCOTT J.
Published: July 2009

In this paper, I present a new argument against inclusive legal positivism. As I show, any theory which permits morality to be a condition on legality cannot account for a core feature of legal activity, namely, that it is an activity of social planning. If the aim of a legal institution is to guide the conduct of the community through plans, it would be self‐defeating if the existence of these plans could only be determined through deliberation on the merits. I also argue that, insofar as inclusive legal positivism was developed as a response to Ronald Dworkin's critique of H. L. A. Hart's theory of law, it was founded on a mistake. For once we appreciate the role that planning plays in legal regulation, we will see that Dworkin's objection is based on a flawed conception of legal obligations and rights and hence does not present an objection that inclusive legal positivists were required to answer.
INTUITIVE NON‐NATURALISM MEETS COSMIC COINCIDENCE
Authors: BEDKE MATTHEW S.
Published: July 2009

Having no recourse to ways of knowing about the natural world, ethical non‐naturalists are in need of an epistemology that might apply to a normative breed of facts or properties, and intuitionism seems well suited to fill that bill. Here I argue that the metaphysical inspiration for ethical intuitionism undermines that very epistemology, for this pair of views generates what I call the defeater from cosmic coincidence. Unfortunately, we face not a happy union, but a difficult choice: either ethical intuitionism or ethical non‐naturalism, but not both.
THE PASSIONS OF PUNISHMENT
Authors: HANNA NATHAN
Published: July 2009

I criticize an increasingly popular set of arguments for the justifiability of punishment. Some philosophers try to justify punishment by appealing to what Peter Strawson calls the reactive attitudes– emotions like resentment, indignation, remorse and guilt. These arguments fail. The view that these emotions commit us to punishment rests on unsophisticated views of punishment and of these emotions and their associated behaviors. I offer more sophisticated accounts of punishment, of these emotions and of their associated behaviors that are consistent with Abolitionism, the view that punishment is unjustified.
Conflicts of Interest and Research Quality of Affiliated Analysts in the German Universal Banking System: Evidence from IPO Underwriting
Authors: Bessler Wolfgang , Stanzel Matthias
Published: July 2009

The quality of equity research by financial analysts is a prerequisite for an efficient capital market. This study investigates the quality of earnings forecasts and stock recommendations for initial public offerings (IPOs) in Germany. The empirical study includes 12,605 earnings forecasts and 6,209 stock recommendations of individual analysts for the time period from 1997 to 2004. The focus of this study is on analysing the potential conflicts of interest that arise when the analyst is affiliated with the underwriter of an IPO. In a universal banking system these conflicts of interest are usually more pronounced and therefore interesting to investigate. The empirical findings for the German financial market suggest that earnings forecasts and stock recommendations of the analysts belonging to the lead‐underwriter are on average inaccurate and biased, indicating some conflicts of interest. Moreover, the stock recommendations of the analysts that are affiliated with the lead‐underwriter are often too optimistic resulting in a significant long‐run underperformance for the investor. In contrast, unaffiliated analysts provide better earnings forecasts and stock recommendations that result in a superior performance for the investor.
Linking employee development activity, social exchange and organizational citizenship behavior
Authors: Pierce Heather R. , Maurer Todd J.
Published: July 2009

The authors examined ‘perceived beneficiary’ of employee development (self, organization) for relationships with employee development activity. Perceived organizational support served as a moderator. The authors conclude that employees may engage in development activities to partly benefit their organization to the extent that a positive exchange relationship exists. Correlational data also show that development behavior is related to organizational citizenship behavior, and this is particularly true for work‐related development activity. This research links employee development with social exchange and organizational citizenship, providing implications for both research and practice.