bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential regulation of trkA and p75 in noradrenergic pelvic autonomic ganglion cells after deafferentation of their cholinergic neighbours
Authors: Keast Janet R. , Kepper Mark E.
Published: July 2009

In rats, following lesion of lumbar or sacral preganglionic axons, many pelvic ganglion cells undergo axogenesis to form baskets of terminals around select populations of nearby ganglion cells. The aim of the current study was to address mechanisms underlying initiation of this sprouting, focusing on a possible role for nerve growth factor (NGF). Immunohistochemical localization of NGF receptors (trkA and p75) showed that virtually all noradrenergic and a minority of cholinergic pelvic neurons expressed both receptors. Terminals immunoreactive for each substance were found in pelvic viscera. In pelvic ganglia, many glial cells expressed p75 but not trkA, and very few lumbar or sacral preganglionic neurons expressed either receptor. Lumbar and/or sacral preganglionic inputs were removed from ganglion cells by cutting the hypogastric, pelvic or both nerves, and tissues analysed 8 days later. Levels of receptor expression in noradrenergic pelvic ganglion cells were estimated by calculating the proportion that were receptor‐immunopositive, and quantifying the intensity of trkA or p75 immunofluorescence. No lesion had a significant effect on trkA expression, however, a marked decrease in p75 occurred after cutting pelvic nerves, i.e. after deafferentation of neighbouring cholinergic neurons. These injuries appeared to cause little overall change in glial p75 expression. This study shows that manipulations that trigger sprouting from noradrenergic pelvic neurons cause downregulation of p75 but not trkA. Interestingly, this is occurring while some of their target organs are synthesizing high levels of NGF. This contrasts with other NGF‐sensitive cells, in which one or both receptor types are upregulated by increased exposure to the ligand. The current study is also the first to show a change in p75 expression in neurons that are neither deafferented nor axotomized.
Central forebrain Fos responses to familiar male odours are attenuated in recently mated female mice
Authors: Halem Heather A. , Cherry James A. , Baum Michael J.
Published: July 2009

Exposure of recently mated female mice to the urinary odours of an unfamiliar male blocks pregnancy (the Bruce effect). The absence of a pregnancy block in response to the stud male's familiar odours depends on an olfactory memory that is formed in the accessory olfactory bulb (AOB) in response to vomeronasal organ (VNO) inputs during mating. Sexually naive Balb/c female mice in pro‐oestrus/oestrus were either placed onto soiled bedding (‘bedding‐only’ females) from, or allowed to mate with, a Balb/c male (‘recently mated’ females). After 42 h, females were placed for 90 min onto clean bedding (controls) or onto soiled bedding from either a C57BL/6 male (unfamiliar bedding) or a Balb/c male (familiar bedding). Significant increases in Fos‐immunoreactivity (Fos‐IR, a marker of neuronal activation) occurred in the medial amygdala and the medial preoptic area (MPA) of ‘bedding only’ females exposed to either unfamiliar or familiar bedding and in ‘recently mated’ females exposed to unfamiliar bedding but not to familiar bedding. This suggests that a mating‐induced memory prevents the later activation by the familiar stud male's odours of neurons in forebrain regions that receive inputs from the VNO–AOB. ‘Bedding‐only’ females later exposed to either familiar or unfamiliar bedding had increased Fos‐IR in the Gαo protein‐expressing basal zone of the VNO whereas no such effect occurred in ‘recently mated’ females. Familiar, as well as unfamiliar, male odours augmented Fos‐IR in significantly more rostral than caudal AOB granule cells in all groups, with the effect being strongest in ‘recently mated’ females exposed to familiar male bedding. This outcome is consistent with the absence of odour‐induced Fos‐IR in forebrain regions of these females and, presumably, the absence of a pregnancy block.
Neurotrophins BDNF and NT‐3 promote axonal re‐entry into the distal host spinal cord through Schwann cell‐seeded mini‐channels
Authors: Bamber Norman I. , Li Huaying , Lu Xiaobin , Oudega Martin , Aebischer Patrick , Xu Xiao Ming
Published: July 2009

To promote axonal regeneration in the injured adult spinal cord, a two‐phase repair strategy was employed to (i) bridge a spinal cord hemilesion cavity with a grafted Schwann cell (SC)‐seeded mini‐channel, and (ii) promote axonal re‐entry into the distal cord by infusing two neurotrophins, BDNF and/or NT‐3, directly into the distal cord parenchyma. Here we report that infusion of two neurotrophins, delivered alone or in combination, effectively promotes axonal outgrowth from SC‐seeded mini‐channels into the distal host spinal cord. When an anterogradely transported marker, PHA‐L or BDA, was injected into the spinal cord 3 mm rostral to the graft, a large number of axons was observed to regenerate from the SC graft into the distal cord in neurotrophin‐treated groups. A subpopulation of these axons was found to grow up to 6 mm within the distal spinal cord. These axons, which were confined mainly within the grey matter, arborized and formed structures which resemble terminal boutons. In channels containing no SCs, the infusion of neurotrophins did not promote axonal ingrowth from the proximal cord stump. In cases which received SC grafts but no neurotrophin infusion, axonal re‐entry into the distal cord was limited. Thus, the present study demonstrates that regenerating axons not only cross a lesion site when a permissive cellular bridge is provided but also penetrate into the distal host spinal cord and elongate for a distance of several cord segments after the infusion of two neurotrophins. The latter event is prerequisite for establishment of appropriate connections between regenerating axons and target neurons and thus, functional recovery.
Increased neuronal and glial expression of protein kinase C isoforms in neocortex of transgenic Tg2576 mice with amyloid pathology
Authors: Roßner S. , Mehlhorn G. , Schliebs R. , Bigl V.
Published: July 2009

We investigated the influence of five‐ to sevenfold neuronal overexpression of the Swedish mutation of human APP695 (APPsw) in the transgenic mouse strain Tg2576 on neocortical protein kinase C (PKC) expression and subcellular distribution. Using specific antibodies to PKCα, PKCβ, PKCγ, PKCε and PKCζ isoforms for Western blot analysis, we observed increased immunoreactivity for PKCα and PKCγ isoforms in crude tissue homogenates from the neocortex of 16‐month‐old APPsw mice as compared with nontransgenic littermates, which was not present in 6 month‐old Tg2576 mice. We also observed elevated levels of PKCα, PKCβ, PKCγ and PKCζ in membrane fractions and reduced concentrations of PKCα and PKCγ in cytosolic fractions of aged Tg2576 mice, indicating that these PKC isoforms are in their activated state. In young, 6‐month‐old Tg2576 mice, however, the increase in membrane‐bound PKC isoforms and concomitant decrease in cytosolic PKC isoforms was much less pronounced, demonstrating the age‐dependent nature of alterations in PKC isoforms. Immunocytochemistry of brain sections supported these findings and revealed increased neuronal labelling for PKCα, PKCγ and PKCλ isoforms in neocortex of 16‐month‐old APPsw mice compared with nontransgenic littermates, with the increase being strongest for PKCγ and PKCλ isoforms. Additionally, PKCγ and to a lesser extent PKCλ isoforms were induced in reactive astrocytes in proximity to amyloid plaques. Our data indicate that neuronal overexpression of APPsw causes a dynamic change in neuronal expression and activation of multiple PKC isoforms known to be regulators of proteolytic amyloid precursor protein (APP) processing (PKCα) and of neuronal survival (PKCλ and PKCζ). The induction of the PKCγ and PKCλ isoforms in reactive astrocytes surrounding amyloid plaques might be required for astrocyte activation and astrocytic cytokine expression in response to amyloid plaque formation.
Behavioural relevance modulates access to spatial working memory in humans
Authors: Ploner Christoph J. , Ostendorf Florian , Brandt Stephan A. , Gaymard Bertrand M. , Rivaud‐Péchoux Sophie , Ploner Markus , Villringer Arno , Pierrot‐Deseilligny Charles
Published: July 2009

Neurophysiological studies in monkeys suggest selective representation of behaviourally relevant information in working memory. So far, no behavioural evidence for this has been reported for humans. Here, we investigated the role of behavioural relevance for access to human visuospatial working memory by using delayed oculomotor response tasks. Subjects were presented two successive visual cues in different and unpredictable locations while fixating on a central fixation point. After a delay, an unpredictable auditory signal (one beep or two beeps) sounded and the central fixation point was turned off, initiating the oculomotor response (i.e. memory‐guided saccade) phase. Two groups of 10 subjects each were studied in two conditions: in the ‘relevant’ condition, subjects were instructed to memorize both visual cues and to move the eyes to the remembered position of the first cue (one beep) or the second cue (two beeps). The same stimuli were used in the ‘irrelevant’ condition, but subjects were instructed to memorize and move the eyes to the position of the first cue only, regardless of the second cue and the auditory signal. In the ‘relevant’ condition, we found a significant increase in errors of memory‐guided saccades to the first cue, when the second cue was located between central fixation point and first cue. This spatially selective interference effect disappeared in the ‘irrelevant’ condition, despite identical stimuli. On a behavioural level, these results show for the first time the significance of behavioural relevance for access to human spatial working memory. These findings complement recent single‐neuron studies in monkeys, showing that the neuronal substrates of working memory selectively represent behaviourally relevant perceptual information.
Predicting the Need for Insulin Therapy in Late Onset (40–69 Years) Diabetes Mellitus
Authors: Lyons T. J. , Kennedy L. , Atkinson A. B. , Buchanan K. D. , Hadden D. R. , Weaver J. A.
Published: July 2009

A six‐year prospective study of 144 newly diagnosed, symptomatic diabetic patients aged 40–69 years showed that 21 (15%) required insulin therapy, commencing 1–61 months after diagnosis. The plasma insulin response to oral glucose was assessed at the time of diagnosis. All 12 patients with very low peak insulin response (≤6 mU/l) required insulin therapy. Thirty‐six patients had an intermediate insulin response (>6≤18 mU/l); of these, 7 with a mean weight 88% (range 73–96%) of average body weight required insulin, while 29 with a mean weight 117% (range 98–158%) of average body weight, did not. Ninety‐six patients had a peak insulin response (>18mU/l); 2 patients whose weights were 96% and 100% of average body weight, required insulin, while the remainder did not. Consideration of initial body weight and peak insulin response provides a useful prediction of the eventual need for insulin.
A Simple Diabetic Clinic Information and Audit System
Authors: Mahler R. F. , Greenwood R. M.
Published: July 2009

A simple method for managing the records of a diabetic clinic in a District General Hospital is described. It is based on a modified manual system in which selected items of data are recorded in a computer system. This provides a Diabetic Register, information for patient and clinical management and for research projects. It simplifies the management of the clinic, is easily used by medical staff inexperienced in the use of computers and causes minimal increase in the clinic workload.
Comparison of Two Commonly Used Insulin Injection Techniques
Authors: Heine R. J. , Sikkenk A. C. , Bilo H. J. G. , Meer J. v. d. , Veen E. A. v. d.
Published: July 2009

In ten patients with insulin‐dependent diabetes we compared postprandial blood glucose levels and plasma free insulin concentrations after the administration of insulin mixtures with two commonly used injection techniques. The morning dose of insulin was administered once using a 13 mm needle, inserted perpendicularly, and once with a 20 mm needle, inserted deep subcutaneously just above the muscle fascia at an angle dependent on the skinfold thickness. Plasma free insulin concentrations and postprandial blood glucose levels were virtually identical for either technique. We conclude, therefore, that the simpler perpendicular method is the technique of choice, saving the diabetics much unnecessary anxiety over a daily procedure.
Sample Preparation and Radioimmunoassay for Circulating Free and Antibody‐bound Insulin Concentrations in Insulin‐treated Diabetics: a Re‐evaluation of Methods
Authors: Collins Andrea C. G. , Pickup J. C.
Published: July 2009

Methods for blood sample preparation and radioimmunoassay of free and antibody‐bound serum or plasma insulin concentrations, using polyethylene glycol (PEG) solution to precipitate bound insulin, have been evaluated and compared. Method A was rapid mixing of whole blood with PEG, followed by separation of bound insulin by centrifugation into Ficoll; method B was rapid PEG addition to whole blood, followed by centrifugation alone; method C was conventional PEG addition to thawed plasma or serum, followed by centrifugation to remove bound insulin. Method A was found to have acceptable performance and reproducibility; serum free insulin levels were not significantly different from those measured by the simpler method B. In samples from insulin‐dependent diabetics, serum free insulin was significantly higher and bound insulin significantly lower in method A compared to the conventional method C. However, in samples from non‐diabetics there was no significant difference between methods A and C. Spurious results were obtained by addition of PEG and assay of plasma and serum samples after either freezing and thawing or incubation at 37°C for 2h, compared to PEG addition and assay of fresh plasma or serum samples. We conclude that conventional, delayed addition of PEG to plasma or serum may result in redistribution of free and bound insulin and that values more representative of in vivo blood insulin levels are obtained by rapid PEG addition methods.
Improved Diabetic Control in Adolescents Using the Penject Syringe for Multiple Insulin Injection
Authors: McCaughey Elizabeth S. , Betts Peter R. , Rowe David J.
Published: July 2009

Eleven adolescent diabetics, aged 15.1 ± 1.3 years (mean ± 1SD) in poor glycaemic control (HbA1 12.0 ± 1.5% at entry) were commenced on a four times daily insulin injection regimen using the Penject fountain‐pen syringe with Initard (50:50 mixture of porcine soluble and isophane) insulin on a sliding scale. Diabetic control improved over a 3‐month period, assessed by a reduction in both the mean preprandial blood glucose concentrations (10.9 ± 3.3 mmol/l to 7.7 ± 2.3 mmol/l) and mean glycosylated haemoglobin concentrations (12.0 ± 1.5% to 9.5 ± 0.9%). Further improvement was again seen in 5 patients who remained on four daily injections for an additional 3 months (mean HbA1: 9.6 ± 0.9% to 8.4 ± 1.0%), whereas diabetic control in 6 patients who returned to twice daily injections deteriorated (mean HbA1 rose from 9.5 ± 1.0% to 10.6 ± 1.6%). Multiple insulin injections using an injection pen are acceptable to adolescent diabetics and improve their control.
Angiotensin‐Converting Enzyme (ACE): Relationship to Insulin‐dependent Diabetes and Microangiopathy
Authors: Toop M. J. , Dallinger K. J. C. , Jennings P. E. , Barnett A. H.
Published: July 2009

Angiotensin‐converting enzyme (ACE) is secreted by the vascular endothelium and serum activity may reflect endothelial damage. A study of 48 insulin‐dependent diabetics, 15 with and 33 without evidence of diabetic retinopathy and 41 non‐diabetic controls was performed. ACE activity was significantly elevated in the diabetics compared with controls (mean ± SD 46 ± 14 vs 35 ± 9 U/I, p<0.001) (units in micromoles substrate converted/min/l serum). This elevation was more marked in diabetics with such evidence of microangiopathy as retinopathy or raised albumin excretion rate (AER) (51 ± 14 U/I, p<0.0001), and also in those with raised AER alone (47.2 ± 15 U/I, p<0.002). Patients with both raised AER and retinopathy had significantly higher ACE activities than those with no complications (53 ± 15 vs 41.2 ± 15 U/I, p<0.05). No correlation was found with glycosylated haemoglobin or smoking habits. We conclude that mean serum angiotensin converting enzyme activity is increased in insulin‐dependent diabetes, particularly in those with evidence of microangiopathy and this may reflect microvascular damage.
Congenital Malformations in Babies of Diabetic Mothers
Authors: Lowy C. , Beard R. W. , Goldschmidt J.
Published: July 2009

In 1979‐80 a national survey of the incidence of congenital malformations in babies born to diabetic mothers in the United Kingdom was carried out by questionnaire. Of the 1034 mothers reported, 773 were known to have diabetes before the index pregnancy. The incidence of congenital malformations ws 7.1% which is significantly higher than the 2.1% in the offspring reported to the Office of Population, Censuses and Surveys (OPCS) for England and Wales in 1979‐80. The increase was most pronounced for malformations of the heart, spine, lungs, and brain. In 40% of the diabetic mothers blood glucose was not recorded during the first trimester of pregnancy, and in this group the malformation rate was twice that in babies born of mothers who had had at least one reported blood glucose estimation during this time. We conclude that there is an urgent need to improve health education and supervision before and during pregnancy in all diabetic women if the prevalence of malformations amongst their offspring is to be reduced.
Haemoglobin A1 and Congenital Malformation
Authors: Stubbs S. M. , Doddridge M. C. , John P. N. , Steel J. M. , Wright A. D.
Published: July 2009

Two hundred and thirty pregnancies were studied in 196 diabetic women. Seven women with babies found to have major malformations had a higher median first trimester haemoglobin A1 (12.9%) than the median HbA1 (10.8%) in those with normal babies (p = 0.06). No relationship was found between the occurrence of minor malformations and first trimester maternal haemoglobin A1. Two of the seven congenital malformations were diagnosed antenatally at a time when therapeutic abortion could be offered. Expert antenatal ultrasound scanning should be offered to all pregnant diabetic women as poor glycaemic control at the time of conception and organogenesis, as evidenced by raised first trimester HbA1, predisposes to congenital malformation.
Retinopathy and Nephropathy in Insulin‐dependent Diabetics: An Inconsistent Relationship?
Authors: Agardh E. , Tallroth G. , Bauer B. , Cavallin‐Sjöberg U. , Agardh C.‐D.
Published: July 2009

The association between retinopathy and nephropathy was investigated in a retrospective study of 52 insulin‐dependent diabetics with preproliferative or proliferate retinopathy and in 48 patients without or with background retinopathy. The duration of diabetes was 23.2 ± 1.0 years (mean ± SEM) and 22.0 ± 1.2 years in the two groups. Patients in the retinopathy group showed a higher frequency of detectable nephropathy and were more often treated with antihypertensive drugs. However, a high proportion (35%) of patients with proliferative retinopathy did not show any detectable signs of nephropathy. Furthermore, nephropathy did not seem to develop in patients with retinopathy during an observation period of up to 9 years. The data suggest that the factors underlying the development of retinal and renal microangiopathy might be of different origin.
Androgen Levels in Men with Diabetes Mellitus
Authors: Semple C. G. , Gray C. E. , Beastall G. H.
Published: July 2009

Patients in varying degrees of diabetic ketoacidosis had low serum testosterone levels which rose following recovery (5.4 ± 1.3 R̊ 13.7 ± 1.7 nmol/l, ρ<0.02, mean ± SE). Blood glucose control of 30 non‐ketotic diabetic men (15 insulin‐dependent and 15 non‐insulin‐dependent) did not correlate significantly with serum testosterone concentrations. Although previous authors had suggested that the adrenal androgen status of diabetic patients might be abnormal, adrenal androgens androstenedione and dehydroepiandrosterone sulphate (DHEAS) were similar in our 30 men to age‐matched healthy men.
Depression and Diabetes
Authors: Robinson N. , Fuller J. H. , Edmeades S. P.
Published: July 2009

The incidence and prevalence of depression in diabetic patients in the United Kingdom is unknown. Since depression may influence blood glucose control which in turn may be related to the development of diabetic complications, it is important to estimate its prevalence in diabetic patients. The prevalence of depression was investigated in a group of Caucasian and West Indian, insulin ‐(IDDM) and non‐insulin‐dependent (NIDDM) adult diabetics and a non‐diabetic comparison group. Prevalence of depression was 8.5% for both groups and a further 19.2% and 14.6%, respectively, had borderline depression. Presence of depression was unrelated to sex, ethnic group, duration or type (IDDM or NIDDM) of diabetes and social class but significantly related to type of accommodation, marital status, and amount of social contact.

A higher percentage of diabetics with psychiatric symptoms had one or more current complications compared to ‘normal’ diabetics. Diabetics suffer from a similar amount of depression to non‐diabetics, but psychiatric symptoms may be related to the frequency of diabetic complications.
The Neurology of Diabetes Mellitus in Central Africa
Authors: Rolfe M.
Published: July 2009

Six‐hundred African diabetic patients were examined; 31% had peripheral neuropathy and 2% autonomic neuropathy. They were older and had had diabetes longer (p<0.001) than those without neuropathy. Blood glucose control, based on HbA1 levels, was poorer (p<0.05) in patients with neuropathy. A control group of 469 non‐diabetic Africans was also examined. They were age‐ and sex‐matched with the diabetic patients aged 35 years or more. Seven per cent had evidence of peripheral neuropathy, significantly less (p<0.001) than the diabetic population. Impotence was commoner in diabetic men than controls, mainly in association with neuropathy and the use of hypotensive drugs.
UK Prospective Diabetes Study V. Characteristics of Newly presenting Type 2 Diabetic Patients: Estimated Insulin Sensitivity and Islet B‐cell Function
Authors:   Multi‐centre Study
Published: July 2009

In 713 newly diagnosed Caucasian diabetic patients aged 25–65 inclusive, insulin sensitivity and islet B‐cell function were estimated from fasting plasma glucose and insulin concentrations by Homeostasis Model Assessment. Insulin sensitivity was reduced in obese subjects. It was also slightly lower in male than in female diabetic patients, in those who were sedentary and in those with high fasting plasma glucose concentrations. The estimated B‐cell function was particularly impaired in patients with a high fasting plasma glucose and in those with normal rather than excess body weight. Whilst diabetes can present in normal weight patients with marked deficiency of B‐cell function, presenting patients often have only a moderate impairment of B‐cell function with markedly impaired insulin sensitivity secondary to obesity, physical inactivity, or being male.
Urinary Ethanol and Diabetes Mellitus
Authors: Alexander W. D. , Wills P. D. , Eldred N.
Published: July 2009

Ethanol concentrations were assayed in urine samples obtained from 10 newly presenting diabetic patients (aged 50–69 years) with glycosuria and symptoms suggesting genito‐urinary candidiasis. No alcohol was detected initially with diabetic urine samples, but when stored at room temperature 8 out of 10 samples showed increasing levels of ethanol from day 3 to day 20. Peak levels were more than 10 000 mg/l in three samples and more than 1500 mg/l in six samples. Studies were also performed using normal urine and urine to which was added glucose and/or Candida. Samples were kept at either room temperature or 4°C for up to 21 days and ethanol assays performed at regular intervals. Studies with non‐diabetic urine showed a maximum ethanol level of 500 mg/l after 11 days only in samples containing both glucose and Candida and kept at room temperature.
Reduced Free Radical Activity Detected by Decreased Diene Conjugates in Insulin‐dependent Diabetic Patients
Authors: Collier A. , Jackson M. , Dawkes R. M. , Bell D. , Clarke B. F.
Published: July 2009

Free radicals are unstable chemical species which react with and oxidize adjacent molecules, particularly polyunsaturated lipids. The diene‐conjugated non‐peroxide isomer of linoleic acid (PL‐9,11‐LA') has been identified as the main diene‐conjugated compound in plasma, and is a probable marker of free radical activity. The aim of the current study was to determine whether the level of PL‐9,11‐LA', measured by HPLC, is altered in insulin‐dependent diabetes, and to investigate whether any abnormality demonstrated correlated with microvascular disease in the form of retinopathy. There was no difference in the concentrations of linoleic acid between the diabetic and control groups (422(129) vs 402(81) (SD) μmol l−1). However, the concentration of PL‐9,11‐LA' was significantly reduced in the diabetic group compared with control group (15.6(6.7) vs 19.3(3.9) μmol l−1, p<0.01), with the molar ratio of PL‐9,11‐LA':Iinoleic acid x 100 similarly reduced (3.8(1.3) vs 5.0(1.6)%, p<0.005). This study does not support the concept that free radicals play a significant role in the development of diabetic vascular disease.
Laboratory, Nurse and Patient Assessment of Glucostix Blood Glucose Reagent Strips
Authors: Wiles P. G. , Stickland M. H. , Birtwell A. J. , Wales J. K.
Published: July 2009

The new Glucostix (Ames) blood glucose reagent strips have been assessed for accuracy and acceptability by nurses using them on the ward and by patients at home. When used with a Glucometer II, Glucostix showed close correlation with blood glucose measured by Yellow Springs Analyser (r = 0.97, p< 0.001). Using the strips without a meter patients achieved a good correlation with the Yellow Springs Analyser when measuring their own capillary blood glucose (r = 0.94, p< 0.001). Ward nurses were less precise (r = 0.87, p< 0.001) and this, perhaps, reinforces the importance of regular quality control to maintain the precision of blood glucose monitoring using reagent strips. Comparing Glucostix with BM Glycemie 1–44 strips, 14 of 15 nurses preferred Glucostix whereas patients showed no overall preference, 37 % preferring BM Glycemie 1–44, 33 % Glucostix, and 30 % stating no preference. There were only minor differences between the two reagent strips. Both groups considered the Glucostix colour change to be easier to read, particularly when using the perforated bench readers, but some thought Glucostix needed more blood and that it was more difficult to remove from the pad. Thus, the Glucostix system provides an accurate measure of blood glucose and is an acceptable alternative to BM Glycemie 1–44 strips for use at home or on the ward.
Case‐control Study on Risk Factors Associated with Fibrocalculous Pancreatic Diabetes
Authors: Vannasaeng S. , Nitiyanant W. , Vichayanrat A.
Published: July 2009

We investigated the relation between fibrocalculous pancreatic diabetes and cassava consumption in a case‐control study, in which 31 cases of pancreatic diabetes were compared with 45 non‐diabetic control subjects who had no pancreatic calcification. Risk of diabetes was not related to cassava consumption. We also observed no increased risk of fibrocalculous pancreatic diabetes associated with alcohol consumption, history of gall bladder and biliary tract diseases, ascariasis, and family history of diabetes. Lower monthly income, farmer occupation, rural residence, and low BMI were significantly (p < 0.05) related to pancreatic diabetes. Our data suggest that consumption of cassava may not be an important risk factor for pancreatic diabetes. With limited sample size, however, cassava consumption could not be excluded as one possible cause of fibrocalculous pancreatic diabetes.
The Effects of Metformin on Adipocyte Insulin Action and Metabolic Control in Obese Subjects with Type 2 Diabetes
Authors: Pedersen Oluf , Nielsen O. Hother , Bak J. , Richelsen B. , Beck‐Nielsen H. , Sørensen N. Schwartz
Published: July 2009

To investigate the mechanisms of action of metformin, insulin receptor binding and the activity of several insulin‐controlled metabolic pathways were measured in adipocytes taken from 10 obese Type 2 diabetic patients treated for 4 weeks with either metformin (0.5 g × 3 daily) or matching placebo using a double‐blind crossover design. Metformin therapy was associated with a significant fall in serum fructosamine levels (3.1±0.4 vs 2.8 ± 0.4 mmol I−1, p <0.02) as well as fasting (10.8 ± 2.4 vs 9.4 ± 2.1 mmol I−1) and daytime (11.5 ± 2.4 vs 10.0 ± 2.2 mmol I−1) plasma glucose concentrations (p <0.05). Fasting and postprandial plasma levels of C‐peptide and insulin were unchanged. While fasting plasma lactate concentrations remained unaltered after metformin, a rise was noted in response to meals (from 1.4 ± 0.1 to 1.8 ± 0.2 mmol I−1, p <0.05). Adipocyte insulin receptor binding was unaffected by drug treatment. Moreover, no insulin‐like effects or post‐binding potentiation of insulin action could be found on adipocyte glucose transport, glucose oxidation, lipogenesis, glycolysis or antilipolysis. A complementary in vitro study using adipocytes from non‐obese healthy volunteers failed to show any direct effect of metformin on adipocyte insulin binding or glucose transport and metabolism, at media drug concentrations corresponding to therapeutic plasma levels.
Activity of the Unstimulated Renin—Angiotensin—Aldosterone System in Type 1 Diabetic Patients with and without Proteinuria
Authors: O'Donnell M.J. , Lawson N. , Barnett A.H.
Published: July 2009

There have been conflicting reports of the activity of the renin‐angiotensin‐aldosterone system in diabetes. We studied the activity of the unstimulated renin‐angiotensin‐aldosterone system in 73 consecutive Type 1 diabetic patients with varying degrees of albuminuria. Patients with elevated albumin excretion rates had elevated median plasma renin activity (macroalbuminuric 2.2, range 0.5–8.2, p < 0.05; microalbuminuric 2.3, 0.7–7.1, p < 0.001; vs normoalbuminuric 1.0, 0.2–4.5 nmol l−1 h−1) and higher systolic blood pressure (macroalbuminuric 141 ± 27 vs normoalbuminuric 116 ± 13 mmHg, mean ± SD, p < 0.01) compared with those with normal albumin excretion rates. Aldosterone secretion and function were normal in all patients studied.
Multiple Daily Insulin Injections Improve Self‐confidence
Authors: Houtzagers C.M.G.J. , Berntzen P.A. , van der Stap H. , van Maarschalkerweerd W.W.A. , Heine R.J. , van der Veen E.A. , Visser A.P.
Published: July 2009

The efficacy and psychosocial effects of multiple daily insulin injections (three preprandial injections of short‐acting insulin (NovoPen) and once daily, bedtime extended‐acting insulin) were compared with those of twice daily combinations of short‐ and intermediate‐acting insulin, in a randomized crossover study (two 6‐month periods), in 16 adult diabetic patients. HbA, was not significantly different for the two treatment modalities (8.2 ± 0.4 vs 7.6 ± 0.4 %). With the pen‐injector regimen significantly less state anxiety (36.0 ± 2.5 vs 39.5 ± 2.7; p < 0.05) was found than with the conventional syringe regimen. The patients tended to experience a better self‐concept as having diabetes (32.0 ± 2.1 vs 37.7 ± 3.0; p < 0.06), as well as less external (‘chance’) orientation (18.5 ± 1.2 vs 20.7 ± 1.6; p = 0.09) with the pen‐injector regimen. A subgroup of patients with lower trait anxiety scores experienced less state anxiety during the pen‐injector regimen than during twice daily insulin injections (30.6 ± 2.6 vs 34.3 ± 2.7; p < 0.05). However, this subgroup tended to be less positive about injecting insulin during the pen‐injector regimen (34.8 ± 3.6 vs 29.6 ± 4.0; p < 0.08). The subgroup with higher trait anxiety scores experienced a better self‐concept as having diabetes (35.3 ± 2.3 vs 40.1 ± 2.6; p < 0.05) and a tendency towards less physician orientation (15.8 ± 1.8 vs 19.6 ± 2.7; p < 0.07) with the pen‐injector regimen. Thirteen patients continued with the pen‐injector regimen.
Non‐invasive Evaluation of Cardiac Function in Young Patients with Type 1 Diabetes
Authors: Fisher B.M. , Cleland J.G.F. , Dargie H.J. , Frier B.M.
Published: July 2009

Cardiac function was evaluated in 40 Type 1 diabetic patients aged less than 30 years and compared with 20 age‐ and sex‐matched control subjects using resting and exercise electrocardiography, and echocardiography. The duration of diabetes was from 0.25 to 25 years (mean 10 years), and few patients had microvascular complications. Left ventricular end‐diastolic and end‐systolic diameters were similar in both groups, with no significant differences between the groups in mean thickness of the intraventricular septum and the posterior wall of the left ventricle. Fractional shortening and mean velocity of circumferential fibre shortening as indices of ventricular function were similar in both groups. Left ventricular hypertrophy (Minnesota Code 3, 1) was observed in the resting electrocardiogram of 22 patients and 12 control subjects (NS), but no other significant abnormalities were observed. One diabetic patient developed asymptomatic ST segment depression during exercise electrocardiography. In conclusion, the chamber size, wall thickness, and systolic function of the left ventricle are normal in most young Type 1 diabetic patients who have few microvascular complications.
Anti‐smoking Programme for Diabetic Patients: The Agony and the Ecstasy
Authors: Fowler P.M. , Hoskins P.L. , McGill M. , Dutton S.P. , Yue D.K. , Turtle J.R.
Published: July 2009

It is generally accepted that people with diabetes should be encouraged to abstain from smoking but there are few data on the best strategy to implement this. In a preliminary survey of our diabetic patients, knowledge of the general and specific health effects of smoking was poor. In a prospective study of 70 diabetic smokers, only 50% agreed to participate in an anti‐smoking programme, and the drop‐out rate was high irrespective of whether the content of the programme was general or specific for diabetes. The enrolment rate was best 2 months after the diagnosis of diabetes and the drop‐out rate was highest in patients recruited immediately following diagnosis. According to self‐reported data, cigarette consumption fell after the first session of the anti‐smoking programme but this could not be verified by the measurement of plasma cotinine. It is concluded that an anti‐smoking counselling programme based on provision of information, within the context of a specialized diabetes centre, is not cost‐effective.
A Trial of the Calcium Antagonist Felodipine in Hypertensive Type 2 Diabetic Patients
Authors: Capewell S. , Hajducka C. , Muir A.L. , Collier A. , Matthews D. , Clarke B.F. , Collier R.
Published: July 2009

Although calcium antagonists may impair insulin releasein vitro, clinical studies have produced conflicting results. Felodipine is a highly selective dihydropyridine calcium antagonist effective in the treatment of hypertension. The efficacy of felodipine was assessed in a double‐blind randomized placebo cross‐over study of 21 Type 2 diabetic patients with primary hypertension, 13 men and 8 women, with an age of 61 (range 46–73) years. Thirteen were controlled on oral hypoglycaemic therapy and 8 on diet alone. Mean (SD) blood pressure (mmHg) was 176(20)/102(8) after a 2–4 week placebo run‐in period, 169(21)/101(8) during the subsequent placebo period compared with 151(15)/88(9) after 4 weeks felodipine therapy (p< 0.001). Nineteen patients required 5 mg twice daily and 2 patients 10 mg twice daily to achieve a target diastolic pressure of 95 mmHg. Side‐effects seen with felodipine included ankle oedema, facial flushing, headache, and dizziness. During oral glucose tolerance tests performed after the felodipine and placebo phases, mean (SD) fasting blood glucose was 9.5(3.1) and 9.0(3.0) mmol I−1, respectively (NS), and the 90 min (peak) blood glucose was 19.1(4.8) and 18.1(4.8) mmol I−1, respectively (NS). Glycosylated haemoglobin and fructosamine concentrations likewise showed no significant changes.
The Natural History and Associations of Microalbuminuria in Type 2 Diabetes During the First Year After Diagnosis
Authors: Patrick A. W. , Leslie P. J. , Clarke B. F. , Frier B. M.
Published: July 2009

The prevalence of microalbuminuria was assessed in 149 consecutive, newly‐diagnosed and untreated patients with Type 2 diabetes, 129 of whom were followed up for 1 year, with at least three urine specimens being obtained during this period. At initial presentation, 39 (26%) patients had a urinary albumin to creatinine ratio (ACR) of > 2.5 mg mmol−1 and compared with patients who had a normal ACR, they were older (64 (11) (SD) vs 58 (11) yr, p < 0.002), with higher random blood glucose (14.4 (4.5) vs 12.3 (4.4) mmol l−1, p < 0.02) and glycosylated haemoglobin (13.0 (3.1) vs 11.3 (2.7)%, p < 0.01) concentrations. An elevated ACR was also associated with a higher systolic blood pressure (149 (22) vs 140 (22), p < 0.05) and the presence of macrovascular disease, particularly peripheral vascular disease (p < 0.001), with this association persisting after adjustment for the effect of age. Ten patients reverted to normal albumin excretion on improving blood glucose control, this group having a significantly higher glycosylated haemoglobin concentration at initial presentation than the group with a persistently elevated ACR (14.4 (2.5) vs 12.0 (3.0)%, p < 0.05). The 21 (16%) patients with a persistently elevated ACR from diagnosis of Type 2 diabetes were older than those with normal albumin excretion throughout (64 (7) vs 58 (10) yr, p < 0.02) and it is probable that these patients have abnormal albumin excretion secondary to established renal pathology.
Important Considerations in the Care of Diabetic Patients in a Developing Country (Nigeria)
Authors: Famuyiwa O. O.
Published: July 2009

Much attention has been focused on the clinical pattern of diabetes mellitus in developing countries. This has its peculiarities especially with regard to tropical pancreatic diabetes, the aetiopathogenesis of which remains speculative. However, more than the clinical pattern of the disease itself, it is the social, economic, and cultural circumstances within which the disease is managed and coped with that give it its ‘tropical’ distinctiveness. Factors of illiteracy, poverty, lack of adequate shelter or source of safe drinking water, poor environmental sanitation, cultural misconceptions about diseases, scarce health resources, non‐availability of drugs or their prohibitive cost, the sale of fake drugs, and of course the ubiquitous traditional and faith healers with their ‘miracle cures’, all combine to create a milieu which is hostile to the optimal management of a chronic lifelong disease like diabetes mellitus. This review focuses on these oft neglected aspects of diabetes because without due attention to them, the successful management of the diabetic patient in most developing countries will remain elusive.
Intraventricular Septal Hypertrophy in Type 1 Diabetic Patients with Microalbuminuria or Early Proteinuria
Authors: Sampson M.J. , Chambers J. , Sprigings D. , Drury P.L.
Published: July 2009

To investigate whether the slightly increased blood pressure that occurs in early diabetic renal disease is associated with hypertensive left ventricular hypertrophy, M‐mode echocardiograms were recorded in 11 non‐diabetic control subjects and four groups of Type 1 diabetic patients. These were 15 patients without microvascular complications, 10 with microalbuminuria, 12 with early persistent proteinuria, and 8 with established renal impairment. Mean blood pressure was 133/80 mmHg (uncomplicated patients), 143/85 mmHg (microalbuminuria), 147/92 mmHg (early proteinuria) and 158/85 mmHg (renal impairment). Mean intraventricular septal width in the uncomplicated diabetic patients was 9.8 (SE 1.2) mm which did not differ from non‐diabetic control subjects. Mean septal width was significantly greater in the other groups (microalbuminuria, 12.7 (1.1) mm, p < 0.02; proteinuria, 12.0 (0.7) mm, p < 0.05; renal impairment, 15.5 (1.8) mm, p < 0.001). Left ventricular mass increased progressively between groups and was significantly increased in those with renal impairment (140 (21) vs 103 (5) g m−2 in uncomplicated patients, p < 0.05). Septal width in the diabetic population not receiving antihypertensives (n = 37) was significantly correlated with systolic blood pressure (r = 0.45, p < 0.005) which was the only variable independently related to septal width and ventricular mass. It appears that the slight increase in blood pressure that occurs in microalbuminuria and early proteinuria is frequently associated with hypertensive left ventricular hypertrophy.
Blood Glycogen and Metabolic Control in Diabetes Mellitus
Authors: Segers O. , Somers G. , Sener A. , Malaisse W. J.
Published: July 2009

The relationship between metabolic control and leukocyte glycogen content in diabetes mellitus was re‐evaluated, blood glycogen being measured by an enzymatic procedure. In 30 healthy subjects, fasting blood glycogen averaged 50.6 ± 2.8 mg l−1 or 7.45 ± 0.42 ng 103‐cells−1, the latter value being unaffected during a 60‐min period of induced hyperglycaemia. Comparable levels were found in 18 Type 1 insulin‐treated diabetic patients (blood glycogen 50.4 ± 4.6 mg l−1, leukocyte glycogen 6.92 ± 0.50 ng 103‐cells−1), 6 insulin‐treated diabetic patients presenting with chronic pancreatitis (blood glycogen 62.2 ± 9.3 mg l−1, leukocyte glycogen 6.69 ± 0.70 ng 103‐cells−1) and 12 Type 2 insulin‐treated patients (blood glycogen 53.7 ± 4.3 mg l−1, leukocyte glycogen 7.51 ± 0.44 ng 103‐cells−1). In severely ketotic patients, leukocyte counts and blood glycogen (160.8 ± 29.6 mg l−1, p < 0.01 vs stable diabetic patients) were increased, but the leukocytic glycogen content was not significantly affected either before or during intensive insulin therapy and rehydration. The leukocyte glycogen content was abnormally low, however, in 9 untreated Type 2 diabetic patients (5.29 ± 0.39 ng 103‐cells−1, p < 0.02 vs healthy subjects) and abnormally high (10.77 ± 0.65 ng 103‐cells−1, p < 0.005 vs healthy individuals) in 30 Type 2 patients treated by sulphonylurea, alone or in combination with insulin. No correlation was found between leukocyte glycogen and either fasting plasma glucose or HbA1c. These findings indicate that blood glycogen is not a reliable index of metabolic control in diabetic patients, and may be affected by factors such as insulin concentration or efficacy, blood glucose level, and sulphonylurea administration.
A Clinical‐histological Study of Individuals with Diabetes Mellitus and Proteinuria
Authors: Taft J.L , Billson V.R. , Nankervis A. , Kincaid‐Smith P. , Martin F.I.R.
Published: July 2009

Coexistent renal pathology with diabetic glomerulosclerosis was found in 38 of 136 (28%) consecutive renal biopsies performed primarily for proteinuria in individuals with diabetes mellitus. The histological lesions found were glomerulonephritis (14), focal tubulointerstitial disease (23), and amyloidosis (1). Significant microscopic haematuria was present in 66% of all patients and did not help to distinguish non‐diabetic disease. The severity of diffuse diabetic glomerular disease was independently associated with duration of diabetes, raised plasma creatinine, the presence of hypertension, clinical retinopathy and neuropathy, but not with type of diabetes, degree of proteinuria or glycosylated haemoglobin at the time of biopsy. Diffuse interstitial fibrosis was related to the severity of glomerular disease and, if severe, also with a significantly (p < 0.01) higher plasma creatinine. Coexisting renal disease was found to be associated with a significantly higher plasma creatinine (p < 0.01) independent of the severity of diabetic glomerulopathy. Coexistent pathology is a not uncommon finding in renal biopsies from diabetic patients with proteinuria. These lesions and their underlying causes may not only influence the renal function and natural history of renal disease in diabetic individuals, but may also determine the response of proteinuria to therapy.
Acute Effects of a Somatostatin Analogue on Kidney Function in Type 1 Diabetic Patients
Authors: Pedersen M. Mau , Christensen S. Engkjær , Christiansen J. Sandahl , Pedersen E. Bjerregaard , Mogensen C.E. , Ørskov H.
Published: July 2009

Suppression of growth hormone by means of somatostatin has been suggested as a possible adjunct therapy in Type 1 diabetes. To assess the acute effect of the somatostatin analogue SMS 201–995 on kidney function in uncomplicated Type 1 diabetes, 13 normoalbuminuric, normotensive diabetic patients were investigated before and during IV infusion of SMS 201–995 (8 μg h−1). A control experiment with infusion of carrier only was also performed. The SMS infusion induced a reduction in the glomerular filtration rate (clearance of 125I‐iothalamate) and renal plasma flow (131I‐hippuran) from 140 ± 15 (mean ± SD) and 550 ± 69 to 131 ± 14 (2p < 0.005) and 492 ± 73 ml min−1 1.73‐m−2 (2p < 0.001), while filtration fraction and total renal resistance rose (both 2p < 0.001). Urinary albumin excretion rate, blood pressure, and blood glucose concentration were unchanged. Plasma growth hormone and glucagon were significantly suppressed. The reduction in glomerular filtration rate and renal plasma flow correlated with the fall in glucagon concentration (r = 0.57, 2p = 0.04, and r = 0.63, 2p = 0.02). The urinary flow rate was markedly reduced, urine osmolality increased, and fractional excretion of sodium, calcium, and phosphate were reduced. Arginine vasopressin, atrial natriuretic peptide, angiotensin II, and aldosterone were unchanged by the SMS infusion.

Thus SMS 201–995 acutely reduces glomerular filtration rate and renal plasma flow in uncomplicated Type 1 diabetes and has an antidiuretic effect. The effects may be related to suppression of glucagon secretion.
Antibodies to Proinsulin and Insulin as Predictive Markers of Type 1 Diabetes
Authors: Kuglin B. , Rjasanowski I. , Bertrams J. , Gries F.A. , Kolb H. , Michaelis D.
Published: July 2009

The aim of the present study was to test whether proinsulin autoantibodies (IgG‐PAA), insulin autoantibodies (IgG‐IAA), and islet cell antibodies (ICA) may be used to identify subjects at risk for Type 1 diabetes. Pre‐diabetic sera from 18 individuals who later developed diabetes were tested. Results were compared with 18 age‐, sex‐, and HLA‐DR‐matched non‐diabetic control subjects from families with Type 1 diabetes. At a mean of 2.4 yr before the onset of diabetes, ICA were found in 13 patients (vs 0 control subjects, p < 0.001), ELISA‐determined IgG‐IAA in 8 patients (vs 1 control subject, p < 0.05) and ELISA‐determined IgG‐PAA in 4 patients (vs 2 control subjects, NS). ELISA‐determined IgG‐PAA do not appear to be useful predictors of the future development of Type 1 diabetes.