bluuebunny/crossref_metadata_2025 huggingface dataset:
Computed Tomographic Anatomy of the Canine Temporal Bone
Authors: Probst A. , Kneissl S.
Published: August 2005

This study aims to identify and describe structures of the temporal bone in normal dogs that can be depicted using computed tomography (CT). Five normal dogs of different breeds and both sexes ranging from 0.5 to 8 years were used as the study material. CT images of 2 mm thickness without abnormalities in the temporal bone were reviewed and analysed in bone and soft tissue settings. All images were compared with corresponding E 12 plastic‐embedded cross sections of 3 mm thickness, which were acquired from anatomic cross sections of frozen beagles. The sections were provided from the Department of Pathobiology (Institute of Anatomy). CT is able to image all relevant bony structures within the temporal bone. Concerning soft tissue structures, CT allows their localization by using bony markers, i.e. the internal acustic meatus for the cranial nerves VII and VIII or the canals for the internal carotid artery and the temporal sinus. The provided reference images are meant to improve orientation within the complex anatomy of the temporal bone. On condition that slice thickness is equal to or smaller than 2 mm and bony setting is supplied, CT is able to visualize all relevant structures within the temporal bone. However, in clinical settings the combined look on air, liquids and bone as well as the contrast enhancement of soft tissues might prefer magnetic resonance imaging to CT.
A Method for Purifying Cochliobolus sativus Cultures Contaminated with Bacteria
Authors: Arabi M. I. E. , Jawhar M.
Published: August 2005

A simple method was developed for purifying Cochliobolus sativus cultures contaminated with bacteria. In this method the contaminated fungal culture is scraped from the surface of the potato dextrose agar (PDA) growth medium. Small leaf pieces (approximately 0.5 cm) of a highly susceptible genotype of barley were placed on the scraped surface of PDA and incubated for 72 h. Disease symptoms of C. sativus were detected on the leaf pieces. Colonies that developed from these pieces on new PDA medium were free from bacteria.
Cascading effects of predator diversity and omnivory in a marine food web
Authors: Bruno John F. , O'Connor Mary I.
Published: August 2005

Over‐harvesting, habitat loss and exotic invasions have altered predator diversity and composition in a variety of communities which is predicted to affect other trophic levels and ecosystem functioning. We tested this hypothesis by manipulating predator identity and diversity in outdoor mesocosms that contained five species of macroalgae and a macroinvertebrate herbivore assemblage dominated by amphipods and isopods. We used five common predators including four carnivores (crabs, shrimp, blennies and killifish) and one omnivore (pinfish). Three carnivorous predators each induced a strong trophic cascade by reducing herbivore abundance and increasing algal biomass and diversity. Surprisingly, increasing predator diversity reversed these effects on macroalgae and altered algal composition, largely due to the inclusion and performance of omnivorous fish in diverse predator assemblages. Changes in predator diversity can cascade to lower trophic levels; the exact effects, however, will be difficult to predict due to the many complex interactions that occur in diverse food webs.
Unlocking the opportunity of tight glycaemic control
Authors: Heine Robert J.
Published: August 2005

The attainment and maintenance of good glycaemic control in both type 1 and type 2 diabetes are major challenges. The main (perceived) barriers of therapy are poor compliance with prescribed medication, hypoglycaemia, fear of insulin injection and fear of self‐testing by finger pricking. Another major issue is the acceptance and uptake of new insulin‐delivery systems and routes of administration. Insulin therapy regimens and insulin preparations are nowadays often chosen because of the ease of delivery. The use of inhaled insulin may, because of the relative ease of administration, facilitate the transfer of type 2 diabetes patients from tablets to insulin, especially in patients with fear or phobia of needles. However, non‐injectable insulin will not automatically be preferred to subcutaneous (SC) insulin injections and a proper assessment of patient acceptance and preference is of great importance. Recent studies suggest that patients may prefer inhaled insulin (Exubera®) over SC insulin. Thus, the availability of inhaled insulin as a potential treatment may increase a patient's willingness to add or change to more appropriate diabetes therapy, which includes insulin. Future studies should be targeted at specific groups of patients who may benefit the most from inhaled insulin, such as those with type 2 diabetes who are delaying initiation or intensification of insulin injections.
Unlocking the opportunity of tight glycaemic control
Authors: Patton John S.
Published: August 2005

As the incidence of diabetes reaches epidemic proportions, the use of new, alternative routes of insulin delivery to manage glycaemic control is becoming an ever more active area of research. The high permeability and large surface area of the lung make it an attractive alternative to subcutaneous (SC) insulin injections. This review discusses the technical factors that influence the efficacy of pulmonary drug delivery and describes how an appreciation of these issues has enabled the design of Exubera®, a novel, non‐invasive, pulmonary dry‐powder human insulin delivery system currently in development by Pfizer and the sanofi‐aventis Group in collaboration with Nektar Therapeutics. While clinical trials of this novel aerosol delivery of insulin are still ongoing in patients with diabetes, the results so far suggest it is simple to use and can provide reproducible doses of insulin in therapeutic amounts with only a few inhalations per dose. In addition, it has been shown to be comparable in terms of efficacy and safety to a conventional SC insulin injection regimen. Delivering aerosolized drugs via the lungs avoids the necessity for SC injections and thereby may increase the patient's acceptability of an insulin‐based therapeutic regimen.
The association between hyperglycaemia on admission and 180‐day mortality in acute myocardial infarction patients with and without diabetes
Authors: Ainla T. , Baburin A. , Teesalu R. , Rahu M.
Published: August 2005

Aim  To evaluate the association between hyperglycaemia on admission, previously known diabetes and 180‐day mortality in acute myocardial infarction (AMI) patients.

Methods  The study population consisted of 779 consecutive AMI patients from the Myocardial Infarction Registry in Estonia who had an admission venous plasma glucose level recorded and who were admitted to the Tartu University Clinics within a period of 2 years. Logistic regression analysis was used to estimate crude and adjusted odds ratios (OR) with 95% confidence interval (95% CI).

Results  In patients without a history of diabetes, glucose level was ≤ 11.0 mmol/l in 556 patients (group 1) and > 11.0 mmol/l in 109 patients (group 2). Of those with diabetes, glucose level was ≤ 11.0 mmol/l in 30 patients (group 3) and > 11.0 mmol/l in 84 patients (group 4). Non‐diabetic hyperglycaemic patients underwent more resuscitations outside of hospital (group 2, 31.2% vs. group 1, 2.0% vs. group 3, 6.7% vs. group 4, 6.0%, P < 0.0001) and had a higher 180‐day mortality compared with other groups (group 2, 47.7% vs. group 1, 14.1% vs. group 3, 26. 7% vs. group 4, 29.8%, P < 0.0001). After adjustment for potentially confounding factors, hyperglycaemic non‐diabetic (OR 4.35, 95% CI 1.79–10.59), but not diabetic (OR 1.79, 95% CI 0.62–5.15) status, remained an independent predictor of 180‐day mortality.

Conclusions  AMI patients with hyperglycaemia on admission, independent of a history of diabetes, represent a high‐risk population for 180‐day mortality. The worst outcome occurs in non‐diabetic hyperglycaemic patients. Further studies are warranted to clarify the questions of hyperglycaemia treatment in AMI patients.
Association between alcohol consumption and serum dehydroepiandrosterone sulphate concentration in men with Type 2 diabetes: a link to decreased cardiovascular risk
Authors: Fukui M. , Kitagawa Y. , Nakamura N. , Kadono M. , Hasegawa G. , Yoshikawa T.
Published: August 2005

Aims  Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with Type 2 diabetes. Both light‐to‐moderate alcohol consumption and higher serum concentrations of dehydroepiandrosterone (DHEA) are associated with reduced CVD mortality, raising the possibility of DHEA as a causal intermediate in CVD and alcohol consumption.

Methods  Relationships between alcohol consumption and serum DHEA sulphate (DHEA‐S) concentration, carotid atherosclerosis as evaluated by carotid ultrasonography and major cardiovascular risk factors were investigated in 404 consecutive men with Type 2 diabetes. Patients were divided into three groups according to mean ethanol consumption per week: non‐drinkers, light‐to‐moderate drinkers (< 210 g per week) or heavy drinkers (≥ 210 g per week).

Results  Plasma HDL‐cholesterol was positively associated with the degree of alcohol consumption. Intima‐media thickness (0.92 ± 0.21 vs. 1.09 ± 0.35 mm, P < 0.0001) and plaque score (3.0 ± 3.3 vs. 5.2 ± 4.9, P = 0.008) were lower in light‐to‐moderate drinkers than in non‐drinkers. Serum DHEA‐S concentrations were higher in light‐to‐moderate drinkers (1264.2 ± 592.2 ng/ml, P < 0.0001) and heavy drinkers (1176.2 ± 607.6 ng/ml, P = 0.0100) than in non‐drinkers (956.8 ± 538.6 ng/ml). In a subgroup aged 60–75‐year‐old patients (n = 277), serum DHEA‐S concentrations were higher in light‐to‐moderate drinkers (1126.8 ± 502.5 ng/ml, P = 0.0121) than in non‐drinkers (937.9 ± 505.1 ng/ml). Also, in a subgroup without CVD (n = 339), serum DHEA‐S concentrations were higher in light‐to‐moderate drinkers (1328.5 ± 593.7 ng/ml, P < 0.0001) than in non‐drinkers (970.1 ± 540.7 ng/ml).

Conclusions  Higher serum DHEA‐S concentrations in light‐to‐moderate drinkers may represent part of the link between light‐to‐moderate alcohol consumption and lower CVD mortality.
Prediction of gestational diabetes mellitus in a high‐risk group by insulin measurement in early pregnancy
Authors: Bitó T. , Földesi I. , Nyári T. , Pál A.
Published: August 2005

Aims  We hypothesized that an increased serum insulin level in early pregancy reflects an increased demand on the compensatory capacity of the pregnant woman, and can serve as a predictor of gestational diabetes mellitus (GDM).

Methods  A 2‐h, 75‐g oral glucose tolerance test (OGTT), with fasting and 2‐h postprandial serum insulin determination, was performed in 71 pregnant women with one or more risk factors for GDM before gestation week 16. In 64 patients, subsequent OGTTs were performed at gestation weeks 24–28, and in the event of a negative result, at gestation weeks 32–34.

Results  Insulin determination at fasting and at 120 min had sensitivities of 69.2% and 92.3%, and specificities of 96.4% and 85.7%, respectively, for the prediction of GDM at gestation weeks 24–28. The sensitivities decreased to 33.3% and 75.0%, respectively, for the prediction of GDM at gestation weeks 32–34. Insulin determination at fasting and at 120 min had positive predictive values of 0.90 and 0.75, respectively, for the prediction of GDM at gestation weeks 32–34. The negative predictive values of fasting and 120‐min serum insulin determination at gestation week ≤ 16 were 0.87 and 0.96, respectively, for the prediction of GDM at gestation weeks 24–28. Increased serum insulin levels both at fasting and 120 min before gestation week 16 were very strong predictive factors for GDM by gestation weeks 32–34 with an odds ratio of 16.6 and 13.3, respectively.

Conclusions  Serum insulin determination at gestation week ≤ 16 is an easy and reliable method with which to predict GDM in a high‐risk group. Despite a negative OGTT, patients with an elevated fasting and/or 120‐min serum insulin level at gestation week ≤ 16 should be managed in the same way as those with GDM. Considering the very high negative predictive value of the method, patients with a normal fasting and/or 120‐min serum insulin level at gestation week ≤ 16 should undergo an OGTT only at gestation weeks 32–34.
Non‐alcoholic hepatic steatosis and its relation to increased plasma biomarkers of inflammation and endothelial dysfunction in non‐diabetic men. Role of visceral adipose tissue
Authors: Targher G. , Bertolini L. , Scala L. , Zoppini G. , Zenari L. , Falezza G.
Published: August 2005

Aims  To compare plasma biomarkers of inflammation and endothelial dysfunction in individuals with and without non‐alcoholic hepatic steatosis (HS), and to evaluate whether such differences were mediated by the adverse metabolic pattern, typically found in these subjects.

Methods  HS (by ultrasound and computed tomography), visceral fat (by computed tomography), insulin resistance (by homeostasis model assessment—HOMA), plasma biomarkers of inflammation and endothelial dysfunction (hs‐C reactive protein, fibrinogen, von Willebrand factor, plasminogen activator inhibitor‐1 activity) were measured in 100 non‐smoking, healthy, male volunteers.

Results  Plasma hs‐CRP, fibrinogen, v‐WF and plasminogen activator inhibitor‐1 (PAI‐1) activity levels were markedly higher (P < 0.01 or less) in subjects with non‐alcoholic HS (n = 35) than in those without HS (n = 65). The former also had significantly higher values for body mass index (BMI), visceral fat, diastolic blood pressure, HOMA insulin resistance score, plasma insulin (both fasting and after glucose load), triglycerides, liver enzymes, and lower high‐density lipoprotein (HDL)‐cholesterol concentration. While the marked differences in these pro‐inflammatory biomarkers observed between the groups were little affected by adjustment for age, BMI, blood pressure values, HOMA insulin resistance score, plasma triglyceride and liver enzyme concentrations, they were completely abolished after controlling for visceral fat. Similarly, in multivariate regression analyses, increased visceral fat significantly predicted the pro‐inflammatory biomarkers, independently of HS and other potential confounders.

Conclusions  These results indicate that, in non‐smoking, non‐diabetic men, the significant increase of plasma biomarkers of inflammation and endothelial dysfunction in the presence of non‐alcoholic HS is largely mediated by abdominal visceral fat accumulation.
Decreased isometric muscle strength after acute hyperglycaemia in Type 1 diabetic patients
Authors: Andersen H. , Schmitz O. , Nielsen S.
Published: August 2005

Aims  Fatigue is a common complaint in diabetic patients during periods of hyperglycaemia. To test whether muscle performance is reduced during acute hyperglycaemia, diabetic patients were studied whilst performing maximal isokinetic and isometric contractions.

Methods  In this double‐blind placebo controlled study, maximal isometric and isokinetic muscle strength was determined in seven Type 1 diabetic patients during normo‐ and hyperglycaemia using a hyperglycaemic clamp technique. On two separate days, maximal muscle strength of the knee extensors was determined quantitatively using a dynamometer. On both days, muscle strength was determined before a constant blood glucose level was obtained and after the blood glucose level had been kept constant at either 5 or 16 mmol/l for 3 h. Percentage of change from baseline at the two glycaemic levels were calculated and compared. In addition, the changes from baseline at these glycaemic levels were related to glucose turnover.

Results  Following hyperglycaemia, a significant decrease in maximal isometric muscle strength was found as compared with normoglycaemia (86 vs. 104% of the initial level) (P = 0.018). In contrast, no alteration of maximal isokinetic muscle strength was found comparing normo‐ and hyperglycaemia (96 and 95%) (P = 0.74). Changes in muscle strength were not significantly related to either basal or hyperglycaemic glucose turnover.

Conclusions  A few hours of hyperglycaemia in Type 1 diabetic patients leads to a reduction of isometric muscle performance, whereas isokinetic muscle strength is unchanged. The reduction in muscle strength could play a role in the development of fatigue and is related more closely to ambient glucose concentrations than to systemic glucose availability.
Excess mortality in Black compared with White patients with Type 1 diabetes: an examination of underlying causes
Authors: Bosnyak Z. , Nishimura R. , Hagan Hughes M. , Tajima N. , Becker D. , Tuomilehto J. , Orchard T. J.
Published: August 2005

Aims  Excess mortality in Type 1 diabetes has previously been found among Black individuals. The aim of the present study was therefore to determine underlying causes.

Methods  A longitudinal study of 1261 [1184 White (93.9%) and 76 Black (6.0%)] individuals diagnosed with Type 1 diabetes between 1965 and 1979, at age < 17 years from the Allegheny County, Pennsylvania and Children's Hospital of Pittsburgh registries. Subjects were contacted in 1999 to determine living status and, where appropriate, cause of death. Living status was determined in 1183 participants (93.8%).

Results  Of the 200 deaths overall, cause of death was determined in 157 subjects (79%); 31 dying from acute and 101 from chronic complications, and 25 from non‐diabetes related causes. Seven deaths were investigated but no cause determined. Black participants had a significantly higher mortality rate compared with White participants for acute complications (hazard ratio = 4.9, 95% confidence interval: 2.0, 11.6), but not for any other cause. There was a temporal decline in the 20‐year mortality rates in both racial groups across the three cohorts diagnosed in 1965–69, 1970–74 and 1975–79.

Conclusions  These results show that the excess mortality in Black people was attributed to acute complications which therefore should be a focus for prevention.
Synergism between mutant HNF1A and the metabolic syndrome in Oji‐Cree Type 2 diabetes
Authors: Pollex R. L. , Hanley A. J. G. , Zinman B. , Harris S. B. , Khan H. M. R. , Hegele R. A.
Published: August 2005

Aims  To determine the prevalence of the metabolic syndrome in the Sandy Lake Oji‐Cree and to examine its interaction with HNF1A in association with impaired glucose tolerance and Type 2 diabetes.

Methods  Using data collected from the Sandy Lake Health and Diabetes Project (1993–1995), the presence or absence of the metabolic syndrome was determined in 515 Oji‐Cree subjects, ≥ 18 years of age. In the original study, fasting plasma analytes were measured, a 75‐g oral glucose tolerance test was administered, and subjects were genotyped for HNF1A G319S.

Results  The unadjusted prevalence of the metabolic syndrome in the Oji‐Cree adults was 29.9%. The adjusted odds ratio (OR) and 95% confidence interval for Type 2 diabetes among subjects who carried the HNF1A G319S mutation and had the modified metabolic syndrome (excluding hyperglycaemia) was 20.3 (6.94, 59.6). Adjusted ORs for Type 2 diabetes for subjects with either the HNF1A G319S mutation alone or the modified metabolic syndrome alone were 5.56 (2.85, 10.9) and 4.84 (2.53, 9.27), respectively. The risk of having impaired glucose tolerance was not influenced by the presence of either factor.

Conclusions  The risk of Type 2 diabetes was similar (approximately five‐fold increased) for subjects with either the presence of the modified metabolic syndrome or the private HNF1A G319S mutation. Interestingly, when present in combination, the two independent risk factors appeared to act synergistically to confer an even greater increased risk of Type 2 diabetes.
The G1888A variant in the mitochondrial 16S rRNA gene may be associated with Type 2 diabetes in Caucasian–Brazilian patients from southern Brazil
Authors: Crispim D. , Canani L. H. , Gross J. L. , Carlessi R. M. , Tschiedel B. , Souto K. E. P. , Roisenberg I.
Published: August 2005

Aim  To compare the frequencies of the G1888A variant in the mitochondrial 16S rRNA gene between patients with Type 2 diabetes and non‐diabetic control subjects from southern Brazil.

Methods  We analysed 520 Type 2 diabetic patients (389 Caucasian– and 131 African–Brazilians) and 530 control subjects (400 Caucasian– and 130 African–Brazilians). DNA samples were amplified by polymerase chain reaction and digested with the RsaI enzyme. Variant frequency in patients and control subjects was compared using χ2 test, Fisher's exact test or odds ratio test. We also investigated the frequency of the G1888A variant in a subgroup of the patients with a maternal history of Type 2 diabetes plus two or more features of maternally inherited diabetes and deafness.

Results  The 1888A allele does not seem to be associated with Type 2 diabetes in African–Brazilians (frequency of 3.8% in patients and 0.8% in control subjects; PFisher = 0.213). However, in Caucasian–Brazilians, the 1888A allele was significantly associated with diabetes (12.3% in patients vs. 3.5% in control subjects; OR = 3.881; 95% CI 2.106–7.164; P < 0.001) and also with higher levels of insulin resistance. The majority of the patients carrying the 1888A allele did not have clinical features of maternally inherited diabetes and deafness.

Conclusion  The present study indicates the association of the mitochondrial G1888A variant with Type 2 diabetes and insulin resistance in Caucasian–Brazilian patients from southern Brazil. However, further studies are required to confirm its effects on mitochondrial function and the role of these effects on the pathogenesis of Type 2 diabetes.
Gestational diabetes: dilemma caused by multiple international diagnostic criteria
Authors: Agarwal M. M. , Dhatt G. S. , Punnose J. , Koster G.
Published: August 2005

Aims  To highlight the variation in the diagnosis of gestational diabetes (GDM) as defined by six well‐accepted international expert panels.

Methods  Two thousand, five hundred and fifty‐four pregnant women underwent a 75‐g oral glucose tolerance test for routine, antenatal GDM screening. They were classified using the criteria of the American Diabetes Association, Australasian Diabetes in Pregnancy Society, the Canadian Diabetes Association, the European Association for the Study of Diabetes, the New Zealand Society for the study of Diabetes and the World Health Organization (WHO).

Results  Between any two criteria, both the GDM prevalence (range; 7.9–24.9%) and the women classified differently [range; 70 (2.7%)−454 (17.8%) women], was significant (P < 0.001). The most inclusive criteria, i.e. Australasian, despite generating the highest prevalence of GDM, did not pick up all the women identified by the most restrictive criteria, i.e. Canadian. The Australasian and the WHO criteria were associated with an increase in the number of Caesarean sections [odds ratio (OR); 1.64, 1.45, respectively] while the American, Canadian and New Zealand criteria identified an increase in macrosomia (birthweight ≥ 4000 g) incidence (OR; 2.09, 2.01, 1.92, respectively).

Conclusions  The guidelines of the various professional committees, being based on consensus and expert opinion, show major discrepancies in their ability to identify women with GDM and their capacity to predict adverse pregnancy outcome. Only evidence‐based criteria derived from reliable and consistent scientific data will eliminate the confusion caused in clinical practice.
Peroxisome proliferator‐activated receptor‐γ co‐activator‐1α (PGC‐1α) gene polymorphisms and their relationship to Type 2 diabetes in Asian Indians
Authors: Vimaleswaran K. S. , Radha V. , Ghosh S. , Majumder P. P. , Deepa R. , Babu H. N. S. , Rao M. R. S. , Mohan V.
Published: August 2005

Aims  The objective of the present investigation was to examine the relationship of three polymorphisms, Thr394Thr, Gly482Ser and +A2962G, of the peroxisome proliferator activated receptor‐γ co‐activator‐1 alpha (PGC‐1α) gene with Type 2 diabetes in Asian Indians.

Methods  The study group comprised 515 Type 2 diabetic and 882 normal glucose tolerant subjects chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population‐based study in southern India. The three polymorphisms were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Haplotype frequencies were estimated using an expectation–maximization (EM) algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies.

Results  The three polymorphisms studied were not in linkage disequilibrium. With respect to the Thr394Thr polymorphism, 20% of the Type 2 diabetic patients (103/515) had the GA genotype compared with 12% of the normal glucose tolerance (NGT) subjects (108/882) (P = 0.0004). The frequency of the A allele was also higher in Type 2 diabetic subjects (0.11) compared with NGT subjects (0.07) (P = 0.002). Regression analysis revealed the odds ratio for Type 2 diabetes for the susceptible genotype (XA) to be 1.683 (95% confidence intervals: 1.264–2.241, P = 0.0004). Age adjusted glycated haemoglobin (P = 0.003), serum cholesterol (P = 0.001) and low‐density lipoprotein (LDL) cholesterol (P = 0.001) levels and systolic blood pressure (P = 0.001) were higher in the NGT subjects with the XA genotype compared with GG genotype. There were no differences in genotype or allelic distribution between the Type 2 diabetic and NGT subjects with respect to the Gly482Ser and +A2962G polymorphisms.

Conclusions  The A allele of Thr394Thr (G → A) polymorphism of the PGC‐1 gene is associated with Type 2 diabetes in Asian Indian subjects and the XA genotype confers 1.6 times higher risk for Type 2 diabetes compared with the GG genotype in this population.
Long‐term (20 years) outcome and mortality of Type 1 diabetic patients in Soweto, South Africa
Authors: Gill G. V. , Huddle K. R. L. , Monkoe G.
Published: August 2005

Aims  To assess the long‐term (20 years) mortality, with causes of death, in a cohort of Type 1 diabetic patients resident in Soweto, South Africa.

Methods  A cohort of Type 1 diabetic patients attending the Diabetic Clinic of Baragwanath Hospital, Soweto were studied in 1982. They were followed over the subsequent 20 years, the final investigation being in 2002. Numbers dying during the period were recorded, as well as year of death and cause. The complication status of survivors was also assessed.

Results  Of the original cohort of 88 Type 1 patients, 21 died during the follow‐up period. There were 39 lost to follow‐up, giving a crude 20 years’ mortality of 43%. Kaplan–Meier analysis showed mortality hazard of 33%. Of those dying, most (9/21) were as a result of renal failure. Other causes were hypoglycaemia (6), ketoacidosis (2), infection (2) and undetermined (2). Of the survivors, comparing data at 0 and 20 years’ follow‐up, there was a significant increase in rates of retinopathy (P < 0.02) and hypertension (P < 0.005), but not of other complications.

Conclusions  This is the first long‐term outcome study of Type 1 diabetes in sub‐Saharan Africa. Although the mortality was substantial, it is similar to equivalent studies of United States (US) Afro‐Americans with Type 1 diabetes. The major cause of death was renal failure related to diabetic nephropathy, and reflects lack of adequate facilities for renal replacement therapy. Despite the deprivation, poverty, political upheaval and recent AIDS epidemic in Soweto, Type 1 diabetes carries a reasonable long‐term prognosis, and survivors are generally free of debilitating complications.
Microvascular endothelial function in subjects with Type 2 diabetes and the effect of lipid‐lowering therapy
Authors: Fegan P. G. , Shore A. C. , Mawson D. , Tooke J. E. , MacLeod K. M.
Published: August 2005

Aims  Abnormalities of microvascular and endothelial function are present in subjects with Type 2 diabetes. Although statin therapy improves cardiovascular risk in diabetes, dyslipidaemia in diabetes may be more responsive to combined statin and fibrate therapy. We examined the effect of cerivastatin and fenofibrate on microvascular function in subjects with Type 2 diabetes with no clinical evidence of cardiovascular disease and near normal lipid levels.

Methods  Age‐, sex‐, lipid‐ and blood pressure‐matched subjects with Type 2 diabetes were randomized in double‐blind fashion to one of four treatment groups: group 1 placebo/placebo (n = 12), group 2 fenofibrate/placebo (n = 10), group 3 cerivastatin/placebo (n = 20) and group 4 cerivastatin/fenofibrate (n = 11). The subjects were recruited from the Lipid in Diabetes Study. Microvascular function was assessed by skin blood flow response to iontophoresis of acetylcholine and sodium nitroprusside and by skin maximum hyperaemia to local heating. Measurements were carried out at baseline and 3 months later.

Results  Although all lipid parameters improved in groups 2–4 after 3 months’ therapy, no difference was detected in skin blood flow to iontophoresis or maximum hyperaemia in any of the groups. Highly sensitive c‐reactive protein (Hs‐CRP) did not change with therapy.

Conclusions  In conclusion, we were unable to demonstrate any improvement in microvascular endothelial function in non‐hyperlipidaemic Type 2 diabetic subjects treated with single or combination lipid‐lowering therapy.

Diabet. Med. (2005)
Effect of a pocket‐size tablet‐dispensing device on glycaemic control in Type 2 diabetic patients
Authors: Maier C. , Mustapic D. , Schuster E. , Luger A. , Eher R.
Published: August 2005

Aim  To evaluate whether a pocket‐size tablet‐dispensing device would improve adherence to therapy as judged by reduction of HbA1c levels in a large population of Type 2 diabetic patients.

Methods  The study design was prospective, randomized, open label with two parallel groups. Patients (2296) were recruited from general practitioners and internists and randomized to either receive a tablet dispenser (TD) or no intervention (control group, CO). Patients’ characteristics and current oral therapy (including dosage) were recorded at baseline. HbA1c was compared between groups at baseline and after 6 months’ intervention.

Results  Data were available in 2081 patients. Baseline characterisitcs, including age, body mass index (BMI), blood pressure and gender distribution were comparable between the two groups, as was HbA1c[7.9 (7.9–8.0), TD vs. 8.0 (7.9–8.0)%, CO, means (95% CI)]. After 6 months, HbA1c improved in both groups, but improvement was significantly greater in TD than in controls [−0.74 (0.67–0.80) vs. −0.53 (0.47–0.59)%, P < 0.0001]. Possession of a dispenser remained an independent predictor of improved control in a multiple regression model. In the subgroup analysis, the effect was significantly more pronounced (i) in patients receiving more medications and (ii) more diabetes medications per day (iii) in younger patients.

Conclusion  In this large study population in a ‘realistic’ setting, a simple tablet‐dispensing device led to a significant and clinically relevant improvement in HbA1c levels. Because patients with a more complex therapy regimen benefited more, we suggest that TD might have improved adherence to therapy.
Islet autoimmunity and genetic mutations in Chinese subjects initially thought to have Type 1B diabetes
Authors: Zhang D. , Zhou Z. , Li L. , Weng J. , Huang G. , Jing P. , Zhang C. , Peng J. , Xiu L.
Published: August 2005

Aims  To explore the contribution of islet autoimmunity and genetic mutations in Chinese patients initially thought to have Type 1B diabetes.

Methods  A group of 33 Chinese patients with newly diagnosed Type 1B diabetes, were identified by the absence of autoantibodies to glutamic acid decarboxylase (GAD), IA‐2, insulin, thyroid globulin or thyroid peroxidase, or high‐risk HLA‐DQ haplotypes. The cohort was further characterized by measurement of autoantibodies to carboxypeptidase H (CPH) and SOX13 using radioligand assays, and testing for genetic mutations associated with MODY3/MODY6 and mitochondrial diabetes. Mutations of HNF‐1α (MODY3) and neuroD1/β2 (MODY6) genes were screened using the single‐strand conformation polymorphism (SSCP) technique and sequencing. Mitochondrial DNA mutations were analysed with polymerase chain reaction—restriction fragment length polymorphism (PCR‐RFLP).

Results  Within the cohort, we found one patient with a novel mutation, R321H (CGC→CAC) in exon 5 of the HNF‐1α gene, one with ND1 mt3316 G→A mutation in mitochondrial DNA, five with Ala45Thr polymorphisms in the neuroD1/β2 gene, and two patients with autoantibodies to SOX13.

Conclusions  Some of the Chinese patients originally thought to have Type 1B diabetes do have other evidence of islet autoimmunity and genetic mutations involved in the underlying aetiology. This suggests that more rigorous screening for these conditions is needed before classifying subjects as having Type 1B diabetes.
Orlistat in the treatment of overweight or obese Chinese patients with newly diagnosed Type 2 diabetes
Authors: Shi Y.‐F. , Pan C.‐Y. , Hill J. , Gao Y.
Published: August 2005

Aims  Orlistat promotes weight loss in overweight and obese patients with Type 2 diabetes receiving hypoglycaemic treatment, but has not been investigated in patients with newly diagnosed and previously untreated Type 2 diabetes. We evaluated the efficacy of 24 weeks’ treatment with orlistat, combined with a mildly reduced‐calorie diet, on weight loss and glycaemic control in overweight and obese patients with newly diagnosed and previously untreated Type 2 diabetes.

Methods  A total of 249 Chinese patients (body mass index 25–40 kg/m2) with recently diagnosed Type 2 diabetes were randomized to placebo (n = 124) or orlistat 120 mg (n = 125) three times daily; all patients followed a mildly reduced‐calorie diet. Patients had HbA1c 6.5–8.5% (mean 7.3%) and had never received any glucose‐lowering medication.

Results  Orlistat‐treated patients achieved significantly greater weight loss at the study end than placebo‐treated patients (−5.4 vs. −2.4 kg; P < 0.0001). More orlistat than placebo patients lost ≥ 5% (60.5 vs. 26.8%; P < 0.0001) and ≥ 10% of their body weight (20.2 vs. 4.9%; P = 0.0002). A significantly greater decrease in HbA1c from baseline was obtained with orlistat than placebo (−1.0 vs. −0.6%; P = 0.0008). Orlistat‐treated patients achieved a significantly greater decrease in fasting plasma glucose (−1.3 vs. −0.5 mmol/l; P = 0.0003) and in the 2‐h oral glucose tolerance test (−4.1 vs. −1.4 mmol/l; P < 0.0001) than placebo recipients. Also, more orlistat‐ than placebo‐treated patients improved from diabetic status to normal or impaired glucose tolerance (44.3 vs. 32.5%; P = 0.0763) after 24 weeks. Orlistat also produced improvements in lipid profiles and waist circumference.

Conclusions  In combination with a mildly reduced‐calorie diet, orlistat significantly reduces body weight, and improves glycaemic control and several cardiovascular risk factors in overweight and obese Chinese patients with newly diagnosed Type 2 diabetes.
Factors associated with insulin discontinuation in subjects with ketosis‐prone diabetes but preserved β‐cell function
Authors: Maldonado M. R. , Otiniano M. E. , Cheema F. , Rodriguez L. , Balasubramanyam A.
Published: August 2005

Aim  To evaluate factors predictive of insulin discontinuation in subjects with ketosis‐prone Type 2 diabetes.

Methods  One hundred and six subjects with ketosis‐prone Type 2 diabetes were recruited during the index episode of diabetic ketoacidosis (DKA). All subjects were followed in a special clinic for at least 6 months. If the subject's glycaemic control reached specified glycaemic goals, exogenous insulin was gradually decreased until discontinuation. Baseline and follow‐up characteristics were compared between the off‐insulin and the on‐insulin groups.

Results  At the end of the follow‐up period (915 ± 375 days) insulin was discontinued in 47% subjects. Subjects in the off‐insulin group were significantly older at the time of diagnosis of diabetes. In the off‐insulin group the majority of subjects were newly diagnosed with diabetes. After 6 months of follow‐up, subjects in the off‐insulin group had significantly lower mean HbA1c, higher mean C‐peptide‐to‐glucose ratio and had more clinic visits per year. In the proportional hazard analysis, new‐onset diabetes [hazard ratio (HR) 1.54; 95% confidence interval (CI) 1.02–2.45], and a higher C‐peptide‐to‐glucose ratio at 6 months of follow‐up (HR 1.77; 95% CI 1.22–2.63) were significant predictors of insulin discontinuation.

Conclusions  In subjects with ketosis‐prone Type 2 diabetes, the best predictors of insulin discontinuation are having new‐onset diabetes, and higher β‐cell functional reserve (as measured by the C‐peptide‐to‐glucose ratio).
Optimal timing of injection of once‐daily insulin glargine in people with Type 1 diabetes using insulin lispro at meal‐times
Authors: Ashwell S. G. , Gebbie J. , Home P. D.
Published: August 2005

Aims  To compare blood glucose control when insulin glargine is given at lunch‐time, dinner‐time, and bed‐time in people with Type 1 diabetes using insulin lispro at meal‐times.

Methods  In this 16‐week, three‐way, cross‐over study, 23 people with Type 1 diabetes were randomized to insulin glargine injection at lunch‐time (L) [mean 12.37 ± 00.34 (± sd) h], dinner‐time (D) (18.12 ± 00.40 h), or bed‐time (B) (22.29 ± 00.40 h), each plus meal‐time insulin lispro. Each 4‐week treatment period concluded with a 24‐h inpatient metabolic profile.

Results  Insulin doses, HbA1c, and fructosamine concentration did not differ between treatment periods. Pre‐breakfast self‐monitored blood glucose (SMBG) concentration was higher with injection of glargine at lunch‐time than at other times [L: 9.2 ± 0.3 (± se) vs. D: 8.2 ± 0.3 or B: 8.0 ± 0.3 mmol/l, P = 0.016], as probably was pre‐lunch SMBG (L: 8.6 ± 0.7 vs. D: 6.4 ± 0.7 or B: 6.4 ± 0.8 mmol/l, P = 0.051). Pre‐dinner SMBG level was higher with dinner‐time glargine than other injection times (D: 9.4 ± 0.9 vs. L: 4.9 ± 0.9 or B: 7.4 ± 1.1 mmol/l, P = 0.007). For 22.00 to 02.00 h, mean inpatient plasma glucose concentration was higher with injection of glargine at bed‐time than other times (B: 9.1 ± 0.6 vs. L: 7.8 ± 0.6 or D: 6.7 ± 0.6 mmol/l, P = 0.023). Plasma free insulin concentration was lower at the end of the afternoon with dinner‐time glargine than other injection times (D: 11.5 ± 1.4 vs. L: 20.2 ± 1.3 or B: 16.5 ± 1.3 mU/l, P < 0.001). Frequency of hypoglycaemia was not different, but timing of hypoglycaemia differed between treatment periods.

Conclusions  Blood glucose levels rise around the time of injection of insulin glargine whether given at lunch‐time, dinner‐time or bed‐time. Bed‐time injection leads to hyperglycaemia in the early part of the night which is improved by giving insulin glargine at lunch‐time or dinner‐time.
Angiotensin II does not affect endothelial tone in Type 1 diabetes—results of a double‐blind placebo controlled trial
Authors: Browne D. L. , Meeking D. R. , Allard S. E. , Munday J. L. , Shaw K. M. , Cummings M. H.
Published: August 2005

Aims  Previously, we have demonstrated that patients with normoalbuminuric Type 1 diabetes are characterized by impaired nitric oxide bioavailability compensated for by increased vasodilatory prostanoid‐mediated vasodilation. Experimental evidence suggests vascular responses to endogenous angiotensin II involve the nitric oxide and prostaglandin pathways. We examined whether selective blockade of angiotensin II influences endothelial tone with particular reference to the nitric oxide/prostaglandin pathways in patients with Type 1 diabetes free from vascular complications.

Methods  At baseline, we studied changes in forearm blood flow in response to brachial arterial infusions of acetylcholine, l‐NMMA, a combination of l‐NMMA and the cyclo‐oxygenase inhibitor indomethacin and nitroprusside in 30 patients with normoalbuminuric Type 1 diabetes [21 male, 9 female; age 38.5 ± 1.9 years (mean ± sem)]. Patients were randomized to 2 weeks’ treatment with placebo or the selective angiotensin II receptor blocking agent irbesartan, 300 mg, prior to forearm vasoactive responses being re‐examined.

Results  The forearm responses to nitroprusside and acetylcholine were unchanged by both placebo (P = 0.23 and P = 0.36, respectively) and irbesartan (P = 0.41 and P = 0.36). Similarily, dose–response curves to acetylcholine in the presense of l‐NMMA alone (P = 0.42) and a combination of l‐NMMA and indomethacin (P = 0.44) were not altered by angiotensin II blockade.

Conclusion  This study demonstrated that physiological blockade of endogenous angiotensin II in Type 1 diabetes does not augment agonist‐evoked vasodilation or the contribution of nitric oxides and prostanoids to endothelial tone.
Diabetes mellitus and impaired glucose regulation in the Canary Islands (Spain): prevalence and associated factors in the adult population of Telde, Gran Canaria1
Authors: Boronat M. , Varillas V. F. , Saavedra P. , Suárez V. , Bosch E. , Carrillo A. , Nóvoa F. J.
Published: August 2005

Aims  To estimate the prevalence and the determinants of diabetes mellitus and impaired glucose regulation (IGR) in an adult Canarian population.

Methods  Cross‐sectional study. One thousand and thirty subjects aged 30–82 years were randomly selected. Participants completed a survey questionnaire and underwent blood pressure measurements, anthropometry, blood samples, and a 75‐g standardized oral glucose tolerance test.

Results  The age‐standardized prevalence of diabetes was 15.8% (95% confidence interval: 11.8–19.8) in men and 10.6% (7.1–14.1) in women. Total prevalence was 13.2% (11.1–15.2). Among individuals with diabetes, 55.4% of men and 38.2% of women were not previously diagnosed. The age‐standardized prevalences of impaired glucose tolerance and impaired fasting glycaemia were 11.4% (9.5–13.4) and 2.8% (1.8–3.8), respectively. In multivariate analyses, age, waist circumference, serum triglycerides, and familial history of diabetes were independently associated with diabetes in both sexes, while a value of C‐reactive protein (CRP) ≥ 1 mg/l showed an association with diabetes, but only in men. Age and triglycerides were related to impaired glucose regulation (IGR) in both sexes, waist circumference was related to IGR exclusively in men, and familial diabetes exclusively in women. Statistically significant interactions between gender and both CRP and triglycerides were found with respect to diabetes, and between gender and both waist circumference and triglycerides for IGR.

Conclusions  Compared with the rest of Spain, the prevalence of diabetes is moderately increased in this area of the Canary Islands. Along with other well‐established risk factors, CRP was independently associated with diabetes, but only in the male population.
Altered chemokine levels in individuals at risk of Type 1 diabetes mellitus
Authors: Hanifi‐Moghaddam P. , Kappler S. , Seissler J. , Müller‐Scholze S. , Martin S. , Roep B. O. , Strassburger K. , Kolb H. , Schloot N. C.
Published: August 2005

Aims  The hypothesis was tested in an exploratory study that individuals at high risk of developing Type 1 diabetes mellitus have altered systemic levels of cytokines and chemokines.

Subjects and methods  Forty‐two non‐diabetic first‐degree relatives of patients with Type 1 diabetes mellitus were recruited. Of these, 18 had multiple islet autoantibodies (islet cell antibody, glutamic acid decarboxylase antibody, IA‐2 antibody). Follow‐up for 9–11 years confirmed high vs. moderate diabetes risk in islet autoantibody‐positive vs. ‐negative relatives. Cytokines and chemokines were determined by enzyme‐linked immunosorbent assay (ELISA).

Results  Serum concentrations of classic Th1‐associated cytokines (IFN‐γ, IL‐12, IL‐18) or Th2/Treg‐associated cytokines (IL‐5, IL‐10, IL‐13) did not significantly differ in high vs. moderate diabetes risk group. However, of six chemokines analysed, levels of CCL3 and CCL4 were increased (P = 0.0442 and P = 0.0334) while CCL2 was decreased (P = 0.0318) in the multiple islet autoantibody‐positive group. No significant differences were seen for CCL5, CCL11, CXCL10. There was a significant correlation between the two closely related chemokines CCL3 and CCL4 in individuals at risk (r = 0.84, P = 0.00005), but not in the autoantibody‐negative group.

Conclusion  Relatives at high risk of developing Type 1 diabetes mellitus have abnormal cellular immune regulation at the level of systemic chemokines. The up‐regulation of CCL3 and CCL4 vs. down‐regulation of CCL2 suggests opposed functions of these chemokines in the disease process. These findings need to be confirmed by independent studies.
NONIDENTITY, WRONGFUL CONCEPTION AND HARMLESS WRONGS
Authors: Markie P. J.
Published: August 2005

Joel Feinberg and Dan Brock have independently developed a solution to the Problem of Nonidentity as it occurs in cases where a mother's negligent act of conception causes her child to be born with a severe disability. I display three problems in the Feinberg‐Brock proposal and develop an alternative view that explains both cases of wrongful conception and additional instances of the Problem of Nonidentity presented by Derek Parfit and others.
BLOCKING THE PATH FROM VAGUENESS TO FOUR DIMENSIONALISM*
Authors: Miller Kristie
Published: August 2005

There is a general form of an argument which I call the ‘argument from vagueness’ which attempts to show that objects persist by perduring, via the claim that vagueness is never ontological in nature and thus that composition is unrestricted. I argue that even if we grant that vagueness is always the result of semantic indeterminacy rather than ontological vagueness, and thus also grant that composition is unrestricted, it does not follow that objects persist by perduring. Unrestricted mereological composition lacks the power to ensure that there exist instantaneous objects that wholly overlap persisting objects at times, and thus lacks the power to ensure that there exists anything that could be called a temporal part. Even if we grant that such instantaneous objects exist, however, I argue that it does not follow that objects perdure. To show this I briefly outline a coherent version of three dimensionalism that grants just such an assumption. Thus considerations pertaining to the nature of vagueness need not lead us inevitably to accept perdurantism.
Activation of latent cyclin‐dependent kinase 5 (Cdk5)–p35 complexes by membrane dissociation
Authors: Zhu Ying‐Shan , Saito Taro , Asada Akiko , Maekawa Shohei , Hisanaga Shin‐ichi
Published: August 2005

Cyclin‐dependent kinase 5 (Cdk5) is a Ser/Thr kinase of increasingly recognized importance in a large number of fields, ranging from neuronal migration to synaptic plasticity and neurodegeneration. However, little is known about its mechanism of activation beyond its requirement for binding to p35 or p39. We have examined membrane interactions as one method of regulating the Cdk5–p35 complex. The kinase activity of Cdk5–p35 is low when it is bound to membranes. The Cdk5–p35 found in rat brain extract associates with membranes in two ways. Approximately 75% of complexes associate with membranes via ionic interactions only, and the remaining 25% associate with membranes via ionic interactions together with lipidic interactions. Solubilization with detergent or high‐salt solution activates Cdk5–p35 several fold, and this activation is reversible. Therefore, membrane interactions represent a novel mechanism for the regulation of Cdk5–p35 kinase activity.