bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement in the Regulation of Cellular Cholesterologenesis in Diabetes: the Effect of Reduction in Serum Cholesterol by Simvastatin
Authors: Owens D. , Stinson J. , Collins P. , Johnson A. , Tomkin G. H.
Published: July 2009

Cellular cholesterol homeostasis was examined in 11 hypercholesterolaemic Type 2 diabetic patients prior to and following reduction of serum cholesterol using simvastatin, an inhibitor of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMGCoA) reductase. Following 12 weeks of treatment with simvastatin (10–40 mg day−1), serum cholesterol decreased by 30 ± 3% from 7.8 ± 0.2 mmol I−1 to 5.5 ± 0.2 mmol I−1 (p < 0.001) and LDL‐cholesterol by 35 ± 4% from 5.7 ± 0.2 to 3.6 ± 0.1 mmol I−1 (p < 0.001). The esterified/free cholesterol ratio in LDL also decreased from 2.75 ± 0.18 to 1.94 ± 0.10 (p < 0.01) after treatment. Cellular cholesterol synthesis, measured by [14C] acetate incorporation into mononuclear leucocytes, decreased by 39 ± 11% from 231 ± 13 to 140 ± 25 μmol g‐protein−1 (p < 0.01). The degree of suppression of [14C]acetate incorporation into cholesterol in normal mononuclear cells by diabetic patients' LDL increased from 32.1 ± 4.0% to 48.8 ± 2.5% (p < 0.001) following simvastatin. The activity of acyl coenzyme A:cholesterol‐0‐acyltransferase (ACAT) increased significantly by 55 ± 18% (p < 0.05) after treatment. Cholesterol synthesis in patients' mononuclear cells correlated positively (r = 0.66, p < 0.05) with the esterified/free cholesterol ratio of their LDL, while suppression of cholesterol synthesis by patients' LDL correlated negatively (r = −0.64, p < 0.05) with the esterified/free cholesterol ratio of the LDL following treatment. Thus, abnormally esterified LDL particles found in hypercholesterolaemic diabetic patients can be modified by the hypocholesterolaemic agent simvastatin and this compositional alteration in LDL is associated with increased cellular cholesterol esterification.
Are Blood Glucose Reagent Strips Reliable in Renal Failure?
Authors: Clark J. D. A. , Goldberg L. , Jones K. , Hartog M.
Published: July 2009

In vitro studies have suggested that a low packed cell volume may cause reagent strips to overestimate blood glucose concentration. The reliability of such strips has therefore been investigated in diabetic patients with end‐stage renal failure, all of whom had low haematocrits (24 ± 4 (± SD)%). Three brands of strips were evaluated and their results were compared with laboratory whole blood glucose concentrations determined on the same samples. All over‐read compared with the laboratory (BM Glycemie 1–44 strips 118 ± 1%, Glucostix 132 ± 2%, ExacTech strips 163 ± 4%) and the percentage over‐read was negatively correlated with the haematocrit for each strip (all p < 0.001).
Birthweight of Babies Born to Mothers with Type 1 Diabetes: is it Related to Blood Glucose Control in the First Trimester?
Authors: Peck R. W. , Price D. E. , Lang G. D. , MacVicar J. , Hearnshaw J. R.
Published: July 2009

A retrospective study of 133 pregnancies in women with Type 1 diabetes was performed, and the 116 which progressed beyond 28 weeks were further analysed. Despite good maternal blood glucose control (mean (± SE) HbA1 levels 8.6 ± 0.2 % at the end of the first trimester; 6.9 ± 0.2 % at delivery; normal range 4.0–8.5 %), 38 % of babies had birthweights above the 90th centile and operative intervention occurred in 77 deliveries (66 %). There was no significant correlation between birthweight and HbA1 level at any stage of pregnancy, but mothers with babies above the 90th centile for weight had a higher HbA1 at the end of the first trimester than mothers with babies below the 90th centile (9.3 ± 0.5 vs 7.9 ± 0.2 %, p < 0.05). In contrast there was no difference in the HbA1 levels at delivery (7.0 ± 0.3 vs 6.8 ± 0.2 %). The perinatal mortality rate was 17.7 per 1000 births. The results confirm that in Type 1 diabetes large babies are common despite good blood glucose control, and suggest that maternal blood glucose control in the first trimester may be an important determinant of birthweight.
Is Hypertension a Major Independent Risk Factor for Retinopathy in Type 1 Diabetes?
Authors: Nørgaard K. , Feldt‐Rasmussen B. , Deckert T.
Published: July 2009

Hypertension is an established risk factor for retinopathy. Whether it is an independent risk factor or acts only by association with nephropathy is not known. Therefore, we studied 273 Type 1 diabetic patients. They were divided into four groups. Group 1 (n = 55) were normotensive and normoalbuminuric, group 2 (n = 51) had hypertension but were normoalbuminuric, group 3 (n = 33) had nephropathy but were normotensive, and group 4 (n = 134) had nephropathy and hypertension. Hypertensive patients with normoalbuminuria (blood pressure 146 ± 19 (± SD)/87 ± 12 mmHg) had the same prevalence of retinopathy as normoalbuminuric normotensive patients (123 ± 12/75 ± 5 mmHg). Hypertensive nephropathic patients (blood pressure 147 ± 18/87 ± 8 mmHg) had more retinopathy than hypertensive normoalbuminuric patients despite similar blood pressure (normal retina/advanced retinopathy: 3 %/73 % vs 46 %/17 %, p< 0.001). Nephropathic normotensive patients had worse retinal changes than hypertensive normoalbuminuric patients (19 %/49 %, p< 0.001) but fewer than the nephropathic hypertensive patients p < 0.001). Thus hypertension per se is not associated with increased retinal changes but may aggravate these in patients with clinical nephropathy.
Screening for Treatable Diabetic Retinopathy: a Comparison of Different Methods
Authors: Buxton M. J. , Sculpher M. J. , Ferguson B. A. , Humphreys J. E. , Altman J. F. B. , Spiegelhalter D. J. , Kirby A. J. , Jacob J. S. , Bacon H. , Dudbridge S. B. , Stead J. W. , Feest T. G. , Cheng H. , Franklin S. L. , Courtney P. , Talbot J. F. , Ahmed R. , Dabbs T. R.
Published: July 2009

The results of the screening of 3318 diabetic patients for sight‐threatening diabetic retinopathy in three UK centres are reported. The aims of the study were to determine the extent of diabetic retinopathy in the screened population and to assess the relative effectiveness of different screening methods in appropriately referring cases from a diabetic population, in a context very close to a routine clinical service. Patients were assessed by ophthalmoscopic examination by an ophthalmological clinical assistant. The clinical assistants' referral grades formed the reference standard against which to assess the effectiveness of other screening methods including ophthalmoscopy by primary screeners who were general practitioners (GPs), ophthalmic opticians and hospital physicians, and the assessment by consultant ophthalmologists of non‐mydriatic Polaroid fundus photography. The performance of primary screeners based on ophthalmoscopy ranged from a sensitivity of 0.41, with a specificity of 0.89, for one of the GP groups, to a sensitivity of 0.67, with a specificity of 0.96, for the hospital physician group. The performance of the non‐mydriatic camera ranged from a sensitivity of 0.35, with a specificity of 0.95, to a sensitivity of 0.67, with a specificity of 0.98.
Importance of the Rate of Hydration of Pharmaceutical Preparations of Guar Gum; a New In Vitro Monitoring Method
Authors: Ellis P. R. , Morris E. R.
Published: July 2009

Dietary supplements of guar gum are known to improve blood glucose control in diabetic patients. The efficacy of guar is probably dependent mainly upon its capacity to hydrate rapidly and thus to increase viscosity in the small intestine post‐prandially. Measurement of the rate of hydration in vitro might therefore be a useful index of the effectiveness of guar formulations. A simple method for monitoring the hydration rate of guar gum has been developed, which involves measuring the changes in viscosity at discrete time intervals over a period of 5 h using a Brookfield RVT rotoviscometer. Six different samples of guar gum (four pharmaceutical preparations and two food grades of guar flour) were hydrated in sealed glass jars rotated at 6 rev min−1 in order to prevent particle aggregation. Marked differences in hydration rate and ultimate (maximum) viscosity between the different guar samples were observed. Three of the four pharmaceutical preparations were lower in viscosity than the food grades of guar flour during the first 60 min of hydration. Two of the preparations hydrated so slowly that even after 5 h they attained viscosity levels of only 60% of their ultimate viscosity. These results may explain why some guar gum preparations are clinically ineffective.
Impact of Late Complications in Type 2 Diabetes in a Dutch Population
Authors: Verhoeven S. , van Ballegooie E. , Casparie A. F.
Published: July 2009

The prevalence of late complications was determined in four general practices in a representative group of 137 patients with Type 2 diabetes and a control group of 128 non‐diabetic individuals. Retinopathy was found in 35 % of all diabetic patients, with the same prevalence below and above the age of 70 years. Microalbuminuria was found in 42 % of diabetic patients and in 22 % of the control group (p < 0.001). Above 70 years of age microalbuminuria was found with increasing frequency in the control group and was not significantly higher in the diabetes group. Serum creatinine was the same in the diabetic patients and the control group. Peripheral neuropathy was found frequently in the diabetes group, but was not uncommon in the control group (abnormal temperature sensation 63 vs 49 % (p < 0.05), abnormal vibration perception 53 vs 33 % (p < 0.001), absent tendon reflex 62 vs 21 % (p < 0.001)). Above age 70 years there was again a reduction in the difference in prevalence of neuropathy between the diabetes and control groups. Ischaemic heart disease was found more frequently in the diabetes group, but only below 70 years of age (32 % of diabetic patients and 14 % of the control group with ischaemic changes on ECG (p < 0.01)). Above that age 46 % of the diabetes group and 45 % of the control group had ECG signs of ischaemic heart disease.
Prevalence and Incidence of Insulin‐treated Diabetes Mellitus in Adults in Canterbury, New Zealand
Authors: Scott R. S. , Brown L. J.
Published: July 2009

A population‐based diabetes register showed a prevalence of insulin‐treated diabetes mellitus (n = 1148) in Canterbury, New Zealand, of 3.3 per 1000 population at 1 January 1984. Median age was 52 years, with equal sex distribution. Eleven percent were aged 0–19 years. Prevalence was highest in those aged 50 years or more, reaching 7.6 per 1000 in the 70–79 years age group. Only 28 % of cases presented with diabetes under 20 years of age. Of those diagnosed in adulthood, only 17 % did not commence insulin therapy as their permanent treatment modality within 12 months post‐diagnosis. Incidence of new insulin‐requiring diabetic cases between 1981 and 1986 (excluding persons commencing insulin more than 12 months after diagnosis) was 12.8 per 100 000 per year. There were two incidence peaks, one in adolescence (16.9 per 100 000), the other in the older age group. Rates in the elderly peaked at 25.9 per 100 000 for males aged 60–69 years, and at 19.5 per 100 000 for females aged 70 or more years. Only 83 of the 268 new cases starting insulin within this period were 0–19 years of age. Based on prevalence surveys of diabetes mellitus in Canterbury, New Zealand, it was determined that 14.3 % of all known adult diabetic people were insulin‐treated.
Absorption of NPH (Isophane) Insulin in Resting Diabetic Patients: Evidence for Subcutaneous Injection in the Thigh as the Preferred Site
Authors: Henriksen J. E. , Vaag A. , Hansen I. Ramsgaard , Lauritzen M. , Djurhuus M. S. , Beck‐Nielsen H.
Published: July 2009

The absorption kinetics of NPH (isophane) insulin injected subcutaneously into the abdominal wall and subcutaneously (SC) and intramuscularly (IM) into the thigh was studied in 11 Type 1 diabetic patients. The thickness of the subcutaneous adipose tissue layer was measured by ultrasound.

NPH (isophane) insulin injected IM into the thigh was absorbed faster than NPH insulin injected SC into the thigh (T50%, IM 8.0 ± 0.6 h and SC 10.3 ± 0.7 h,p< 0.05). No difference in T50%values was found for injection into the abdominal wall (9.7 ± 1.2 h) compared with the thigh. The mean absorption rate from 1.5 to 13.5 h after injection was higher after injection IM into the thigh (6.4 ± 0.3 % of initial dose injected absorbed per h) than after SC injection into the thigh (5.2 ± 0.3 % h−1) and SC into the abdominal wall (5.1 ± 0.3 % h−1) (p<0.01). The most constant absorption rate was obtained after SC injection into the thigh (within‐study day CV of the mean absorption rate 19.9 ± 3.2 % vs 34.4 ± 3.2 % after IM injection into the thigh and 27.1 ± 4.9 % after SC injection into the abdominal wall (p< 0.02)). The study provides further evidence that the subcutaneous tissue of the thigh is the preferred injection site for NPH insulin.
The Production of Immunoreactive α‐and γ‐Interferon by Circulating Mononuclear Cells in Type 1 Diabetes
Authors: Toms G. C. , Baker P. , Boucher B. J.
Published: July 2009

Using a specific immunoradiometric assay method the in vitro alpha interferon response to polyinosinic:polycytidilic acid (poly‐I:C) and the gamma interferon response to concanavalin A were measured in peripheral blood mononuclear cells from 11 healthy matched pairs of Type 1 diabetic patients and normal subjects. The α‐interferon response to poly‐I:C was significantly higher in the diabetic group (median 3.7 (range < 1–25.7) u ml−1) than in the normal group (1.1 (< 1–15.4) u ml−1, p < 0.01). The mean γ‐interferon response to concanavalin A was 64.3 ± 46.9 (± SD) u ml−1 in the diabetic patients and 49.4 ± 18.5 u ml−1 in the normal group (NS). The higher α‐interferon response to poly‐I:C in the diabetic patients was not related to blood glucose concentration, HbA1, age of onset of diabetes, duration of diabetes, or islet cell antibody positivity, and may therefore indicate intrinsic hyper‐responsiveness of circulating mononuclear cells in Type 1 diabetes.
Autoantibodies to Islet Amyloid Polypeptide in Diabetes
Authors: Clark A. , Yon S.M. , de Koning E.J.P. , Holman R.R.
Published: July 2009

Islet amyloid polypeptide (IAPP) is the constituent peptide of amyloid in pancreatic islets of Type 2 diabetic patients and in insulinomas. Amyloid formation in Type 2 diabetes is associated with islet cell destruction which may promote formation of autoantibodies to IAPP. An ELISA method has been developed to detect IAPP autoantibodies and used to assay serum from 80 non‐diabetic subjects, 49 Type 1 and 228 Type 2 diabetic patients, and 10 patients with insulinomas. Microtitre plates coated with IAPP1–37 were used to detect antibody binding followed by an alkaline phosphatase conjugated anti‐human IgG. ELISA binding decreased with sample dilution and with pre‐incubation of the samples with IAPP. The optical density of the substrate reaction was compared with results from a standard serum from a non‐diabetic subject (OD ratio). Elevated OD ratios were detected in some subjects from each patient group but the Type 2 diabetic group had significantly higher titres than the non‐diabetic subjects (p < 0.001). The OD ratio was elevated (> mean + 2SD non‐diabetic group) in 15% of Type 2 and 18% of Type 1 diabetic patients and in 20% with insulinomas. IAPP antibody levels did not correlate with age or gender of subjects, or duration of diabetes. IAPP autoantibodies could be an additional marker for B‐cell damage in diabetes.
Attitudes and Intentions of UK General Practitioners to Diabetes Care at the Time of Implementation of their New Contract
Authors: McMahon C. , Bodansky H.J.
Published: July 2009

Prior to the introduction of their new contract, the intentions of general practitioners in Leeds (UK) towards diabetes care were assessed. All general practices in one Health District (n = 74) were contacted. Assessment was made of 46 (62%), while 28 expressed lack of interest. Of the 46 assessed, 2 (4%) were single‐handed, and 44 (96%) were group practices, and list size was 700–15 500. Practice nurses were employed in 44 (96%) practices. There were 35 (76%) practices which expressed an interest in starting a diabetic clinic, while 6 (13%) had established a clinic. Practice facilities necessary to establish and run a clinic were surveyed. Those available were: register of diabetic patients in 12 (26%) (six of which were incomplete); blood sampling facilities in 45 (98%); blood glucose reagent strips in 45 (98%); glucose meters in 21 (46%) (but five with inappropriate test strips). All practices could check urine, blood pressure, and fundi (dark room available in 40 (87%) practices). Access to dietetic and chiropody services on the premises was available in 19 (41%) and 17 (37%) practices, respectively. Some expertise in diabetes was claimed by only 10 (22%) doctors. Staff at all practices desired further training in diabetes. In conclusion, despite the interest of most practices in starting a diabetic clinic, access to dietetic and chiropody services was inadequate. Expertise was generally lacking, but enthusiasm and desire for training were strong.
BOOK REVIEWS
Authors: Hadden D.R.
Published: July 2009

Book reviewed in this article:

Diabetes and Endocrinology in Clinical Practice by W.M.G. Tunbridge and P.D. Home. Edward Arnold, Hodder & Stough‐ton
In Vitro and In Vivo Potency of Insulin Analogues Designed for Clinical Use
Authors: Vølund Aa. , Brange J. , Drejer K. , Jensen I. , Markussen J. , Ribel U. , Sørensen A. R. , Schlichtkrull J.
Published: July 2009

Analogues of human insulin designed to have improved absorption properties after subcutaneous injection have been prepared by recombinant DNA technology. Five rapidly absorbed analogues, being predominantly in mono‐ or di‐meric states in the pharmaceutical preparation, and a hexameric analogue with very low solubility at neutral pH and slow absorption, were studied. Receptor binding assays with HEP‐G2 cells showed overall agreement with mouse free adipocyte assays. Two analogues, B28Asp and A21Gly + B27Arg + B30Thr‐NH2, had nearly the same molar in vitro potency as human insulin. Another two showed increased adipocyte potency and receptor binding, B10Asp 194% and 333% and A8His + B4His + B10Glu + B27His 575% and 511%, while B9Asp + B27Glu showed 29% and 18% and the B25Asp analogue only 0.12% and 0.05% potency. Bioassays in mice or rabbits of the analogues except B25Asp showed that they had the same in vivo potency as human insulin 1.00 IU = 6.00 nmol. Thus the variation in in vitro potency reflects the differences in receptor binding affinity. Relative to human insulin a low concentration is sufficient for a high affinity analogue to produce a given receptor complex formation and metabolic response. In conclusion, human insulin and analogues with markedly different in vitro potencies were equipotent in terms of hypoglycaemic effect. This is in agreement with the concept that elimination of insulin from blood and its subsequent degradation is mediated by insulin receptors.
Impaired Glucose Tolerance is Characterized by Multiple Abnormalities in the Regulation of Intermediary Metabolism
Authors: Krentz A. J. , Singh B. M. , Nattrass M.
Published: July 2009

The responses of circulating intermediary metabolites to a low‐dose sequential insulin infusion (basal, 0.005, 0.01, and 0.05 U kg‐1 h‐1) were assessed in eight non‐obese men with Impaired Glucose Tolerance (IGT), and in eight healthy control subjects with normal glucose tolerance matched for age, gender, and body mass index. Fasting hyperinsulinaemia was observed in the subjects with IGT (7.4 ± 1.0 vs 2.9 ± 0.3 mU l‐1, p < 0.001). While there was no significant difference (p < 0.1) in fasting venous glucose levels between the groups, fasting concentrations of lactate (p < 0.02), alanine (p > 0.01), and glycerol (p < 0.05) were significantly elevated in the subjects with IGT. During the incremental insulin infusion, overall concentrations of glucose (p < 0.05), lactate (p < 0.05), alanine (p < 0.05), glycerol (p < 0.05), immunoreactive insulin (p < 0.001), and C‐peptide (p < 0.01) were significantly higher in the subjects with IGT. Linear dose–response relationships (p < 0.005) for circulating immunoreactive insulin (log) vs metabolite concentrations were demonstrated by analysis of variance for glucose, non‐esterified fatty acids (NEFA), glycerol, and total ketone bodies. For glucose, glycerol, and NEFA, group dose–response regression lines for the subjects with IGT were displaced significantly to the right (p < 0.001 for each) of those for the normal control subjects, implying insulin insensitivity. In addition to the recognized defect in glucose homeostasis, these results indicate impaired regulation of multiple aspects of intermediary metabolism including lipolysis in IGT.
Capillary and Venous Blood Glucose Measurements Using a Direct Glucose‐sensing Meter
Authors: Matthews D. R. , Burton S. F. , Bown E. , Chusney G. , Dornan T. , Gale E. A. M. , McKinnon G. , Steemson J.
Published: July 2009

The aim of the study was to evaluate the precision and accuracy of the ExacTech home blood glucose meter when used with either capillary or venous blood and to compare this with a reference whole blood glucose assay. Non‐fasting glucose measurements were used since a validation study showed no capillary‐venous differences between fasting and postprandial states. In a cross‐sectional study, blood was taken from 182 patients and measured in duplicate on three batches of strips. Altogether we analysed 1089 readings. The regression of the data from capillary blood samples (meter vs reference method) had a correlation coefficient of 0.93, and a mean bias of 0.2 mmol l‐1. The corrected 90% confidence interval was ± 1.5 mmol l‐1 overall, and ± 0.9 mmol l‐1 for readings under 7.0 mmol l‐1. Regression of the data from venous blood samples (meter vs reference method) had a correlation coefficient of 0.93 and a slope of x 1.1. The corrected 90% confidence interval was ± 1.7 mmol l‐1. Thus venous blood may be used even though the meter is calibrated for capillary samples but the value must be corrected by dividing by 1.1. Error‐grid analysis showed that day‐to‐day clinical decisions could be made on the basis of ExacTech readings, although a diagnosis of borderline diabetes may not be possible.
Screening for Diabetic Retinopathy
Authors: Owens D. R. , Dolben J. , Young S. , Ryder R. E. J. , Jones I. R. , Vora J. , Jones D. , Morsman D. , Hayes T. M.
Published: July 2009

There is a need for greater educational emphasis, both at undergraduate and postgraduate level, on the detection of diabetic eye disease, in particular diabetic retinopathy. The early diagnosis of the sight‐threatening lesions of proliferative retinopathy and maculopathy is a prerequisite for the prevention or reduction of the visual loss and blindness associated with this diabetic complication. It is also essential that patients are aware that diabetes can result in visual loss due to diabetic retinopathy. Patients should understand that diabetic retinopathy may be present without ophthalmic or diabetic symptoms and that its incidence increases with duration of diabetes, poor diabetes control, and hypertension. They must also be aware that, if detected early, retinopathy can be treated successfully and vision preserved. Early detection depends on regular eye examination involving both visual acuity assessment and ophthalmoscopy through dilated pupils by experienced personnel. A comprehensive programme of screening followed by prompt and adequate treatment would made a significant contribution to eradicating diabetic retinopathy as a cause of blindness.
The Epidemiology and Prevalence of Diabetic Retinopathy in the Veneto Region of North East Italy
Authors: Segato T. , Midena E. , Grigoletto F. , Zucchetto M. , Fedele D. , Piermarocchi S. , Crepaldi G. ,   Veneto Group for Diabetic Retinopathy
Published: July 2009

The prevalence of diabetic retinopathy and its relationship to a number of risk factors were examined in a population‐based study in the Veneto region of North East Italy. Of 1321 diabetic patients selected, 98% attended for examination. Prevalence of diabetic retinopathy was 26.2% (24.4% background and 1.8% proliferative). The prevalence of retinopathy was significantly related (p < 0.01) to the duration of diabetes (17.3% for < 5 years; 60.8% for > 20 years). Proliferative retinopathy was much more prevalent after 20 years of diabetes. After 10 years most proliferative retinopathy was found in Type 1 diabetic patients, but before 10 years from diagnosis it was most prevalent in Type 2 diabetes. The prevalence of retinopathy was significantly related (p < 0.001) to the type of diabetes and was found predominantly in Type 1 (46.2%) and insulin‐treated Type 2 (45.9%) subjects and to a lesser degree in non‐insulin‐treated patients (24.6%). The prevalence of retinopathy was significantly related to both fasting and post‐prandial blood glucose levels (p < 0.001), blood urea nitrogen (p < 0.05), and systolic (p < 0.001) and diastolic (p < 0.01) blood pressure. No significant differences were found in the prevalence of total or proliferative retinopathy between males and females. No significant relationships were found with family history of diabetes, alcohol intake, smoking habits, cholesterol, triglycerides, and serum uric acid.
Diabetic Retinopathy: Methodologies in Practice
Authors: Cathelineau G. , Cathelineau B. Villatte
Published: July 2009

In France, 20% of patients with diabetes are monitored by diabetologists, and of these 88% are screened for retinopathy by fundal examination with dilation of pupils and 78% by fluorescein angiography. Colour retinal photography is performed in 24% of cases. Eye examination is performed every year in 85% of patients. Diabetic retinopathy is generally considered to be a vascular disease causing loss of vision by macular oedema, vitreous haemorrhage or retinal detachment. However, it may also be a neurosensory disorder, with functional changes occurring before anatomical vascular abnormalities. These include changes in colour vision, contrast sensitivity, dark adaptation, visual‐evoked potentials, electroretinography, nyctometry, and fluorometry. The majority of these methods have a predictive value for the late onset of retinopathy in diabetic patients.
Aspects of Autonomic Neurophysiology in Diabetic Polyneuropathy: A Brief Review
Authors: Fagius J.
Published: July 2009

The autonomic nervous system is a very diverse system, governing many organs according to endogenous and environmental demands. Consequently autonomic dysfunction in diabetic polyneuropathy is many faceted. Assessment of autonomic nerve function, by testing the reflex responses of autonomic effector organs, should preferably take this differentiation into account. Microneurography allows direct study of the normal and disturbed physiology of two subdivisions of the sympathetic nervous system: signals in muscle nerve fascicles involved in cardiovascular homeostasis, and impulses in skin nerve fascicles involved in body thermoregulation. Observations made with this research tool emphasize the functional differentiation of the autonomic nervous system, and the technique can be used to elucidate pathophysiological mechanisms in disorders such as diabetic polyneuropathy.
Non‐cardiac Autonomic Tests in Diabetes: Use of the Galvanic Skin Response
Authors: Macleod A. F. , Smith S. A. , Cowell T. , Richardson P. R. , Sonksen P. H.
Published: July 2009

Diabetic peripheral neuropathy affects both large myelinated and small unmyelinated nerve fibres. It has been proposed that the small unmyelinated fibres, responsible for pain and temperature sense, and autonomic function, are involved early, particularly in subjects with painful symptoms, and may be important in foot ulceration. The sympathetic skin response has been used to investigate the function of small unmyelinated sympathetic fibres in the limbs of diabetic subjects. Changes in skin resistance at the fingers and toes have been measured simultaneously after a sound stimulus. These procedures were controlled using a microcomputer. Data collected from 55 diabetic subjects, randomly selected from the diabetic clinic, have been compared with results from conventional tests of large motor and sensory fibres and autonomic function. The ratio of the change in skin resistance for toes to fingers correlated with sural and posterior tibial nerve conduction velocity (correlation coefficients 0.54 and 0.42, p < 0.001 and p < 0.01, respectively), with the expired to inspired ratio (correlation coefficient 0.51, p < 0.01), and inversely with vibration perception threshold in the feet (correlation coefficient 0.50, p < 0.001). Correlation with the dark adapted pupil diameter, however, only just achieved statistical significance (correlation coefficient 0.27, p = 0.043). We propose that this simple test may elucidate the role of the peripheral autonomic system in diabetic neuropathy.
Cold and Warm Cutaneous Sensation in Diabetic Patients
Authors: Ijff G. A. , Bertelsmann F. W. , Nauta J. J. P. , Heimans J. J.
Published: July 2009

The assessment of cutaneous thresholds for thermal sensation is now recognized as a valuable method to detect small nerve fibre function in diabetes. Methods commonly used do not allow separate measurements of warm and cold perception. However, there is evidence that the fibre subtypes which signal cold and warm sensation are different (A‐delta‐fibres and C‐fibres, respectively). To investigate if diabetes affects cold and warm sensation equally, thresholds were assessed separately in 30 diabetic patients (age 47.9 ± 15.1 (± SD) years; duration of diabetes, 19.1 ± 13.3 years). Comparisons were made with 71 non‐diabetic control subjects (age 59.7 ± 22.1 years). Thermal discrimination thresholds for cold and warm sensation were determined for the left foot with a two‐alternative forced choice method. In both diabetic patients and in the control group cooling thresholds were smaller than warming thresholds. In diabetic patients log thermal discrimination thresholds for warmth increased 0.1 per decade (p < 0.001), a relationship comparable to that seen in non‐diabetic patients. There was no relationship between cooling thresholds and age in diabetic patients despite a significant (p < 0.001) deterioration with age in control subjects. This difference in the influence of age on cold sensitivity was significant (p < 0.03). Both warm and cold sensation were not related to the duration of diabetes. We conclude that assessment of warm threshold is preferred for the detection of minor disturbances of small nerve fibre function in diabetes.
Cardiovascular Autonomic Dysfunction: Diagnosis and Prognosis
Authors: Broadstone V. L. , Roy T. , Self M. , Pfeifer M. A.
Published: July 2009

The symptoms of cardiovascular autonomic dysfunction may be subtle and occur late in the course of diabetes. They include abnormal exercise‐induced cardiovascular performance, postural hypotension, and cardiac denervation syndrome. Autonomic nervous system testing involves an evaluation of the responses of complex reflex pathways. Some of the most commonly used and validated cardiovascular autonomic tests are RR‐variation, the Valsalva manoeuvre, and postural testing. Sinus arrhythmia during breathing is termed RR‐variation. in diabetic patients with autonomic neuropathy the magnitude of the RR‐variation is decreased. Abnormal exercise‐induced cardiovascular performance has been observed in diabetic subjects with abnormal RR‐variation due to autonomic neuropathy. The Valsalva manoeuvre consists of forced expiration against a standardized resistance for a specified period of time. The reflex bradycardia that follows the Valsalva period in normal subjects is lacking in diabetic patients with clinical evidence of autonomic neuropathy. Postural hypotension in diabetics may be due to neuropathy or to a variety of secondary causes. An algorithm is presented to facilitate assessment of diabetic patients with postural symptoms. Treatment of postural hypotension should be directed primarily to the correction of secondary causes, in the absence of which the symptoms can be controlled by mechanical measures, plasma volume expansion, and vasoconstriction. Cardiac denervation syndrome may result in denervation supersensitivity and afferent (pain) nerve dysfunction. The RR‐variation is a sensitive indicator of impairment of cardiac autonomic innervation and is a simple method for identifying asymptomatic patients at risk for painless ischaemia. Formal cardiovascular stress testing may be prudent before initiating an exercise programme in such individuals.
The Influence of Hypoglycaemic Agents on the Growth and Metabolism of Human Endothelial Cells
Authors: Petty R.G. , Pearson J.D.
Published: July 2009

Using human umbilical vein endothelial cells, and human microvascular endothelial cells from omental and subcutaneous fat obtained at laparotomy, we studied the effects of sulphonylureas and the biguanide metformin on endothelial cell proliferation, prostacyclin production, ecto‐5′‐nucleotidase activity, and von Willebrand factor release. Each drug produced a concentration‐dependent proliferation of umbilical vein but not of microvascular endothelial cells. The stimulation of umbilical vein endothelial cell proliferation by sulphonylureas, but not by metformin, was serum‐ and insulin‐dependent. Sulphonylureas and metformin had no effect on the proliferation of human dermal fibroblasts, smooth muscle cells derived from the umbilical artery, or 3T3 cells, until concentrations > 100 fold those found in vivo were reached, when there was inhibition of proliferation. These agents had no effect on prostacyclin or von Willebrand factor production, or on ecto‐5′‐nucleotidase activity, until high concentrations were used, at levels which also inhibited proliferation. The results suggest that the sulphonylureas and metformin, may, at concentrations found in vivo, induce changes in the turnover of endothelial cells from large vessels, but not of microvascular endothelial cells.
A Simple Method for Quantitation of Insulin Sensitivity and Insulin Release from an Intravenous Glucose Tolerance Test
Authors: Galvin P. , Ward G. , Walters J. , Pestell R. , Koschmann M. , Vaag A. , Martin I. , Best J.D. , Alford F.
Published: July 2009

Both insulin secretion and insulin sensitivity are important in the development of diabetes but current methods used for their measurements are complex and cannot be used for epidemiological surveys. This study describes a simplified approach for the estimation of first phase insulin release and insulin sensitivity from a standard 40‐min intravenous glucose tolerance test (IVGTT), and compares these parameter estimations with the sophisticated minimal model analysis of a frequently sampled 3‐h IVGTT and the euglycaemic clamp technique. For the simplified IVGTT, first phase insulin release was measured as the insulin area above basal post glucose load unit−1 incremental change (i.e. peak rise) in plasma glucose over 0–10 min, and insulin sensitivity as a rate of glucose disappearance (Kg) unit−1 insulin increase above basal from 0–40 min post‐glucose load in 18 subjects who were studied twice, either basally or in a perturbed pathophysiological state (i.e. pre‐ and post‐ultramarathon race, n = 5; pre‐ and post‐20 h pulsatile hyperinsulinaemia, n = 8; pre‐ and post‐thyrotoxic state, n = 5). A further 12 subjects were compared by IVGTT, and glucose clamp. In addition, seven dogs were studied three times by IVGTT during normal saline infusion and after short‐term (1/2 hour) or long‐term (72 hour) adrenaline infusions. First phase insulin release and insulin sensitivity estimated from the simplified IVGTT as calculated by the two methods correlated closely (rs = 0.89 and rs = 0.87, respectively), although less precisely in markedly insulin‐resistant subjects and the slopes and y intercepts of the linear regression lines were similar in the basal and perturbed states. Insulin sensitivity measured by the shortened 40 min IVGTT and glucose clamp techniques were also comparable for the whole group (rs = 0.85), and for hypoinsulinaemic‐glucose intolerance subjects (rs = 0.96). It is concluded that the shortened simple IVGTT method is practical, gives reliable simultaneous estimates of glucose tolerance, first phase insulin secretion and insulin sensitivity in a diverse group of individuals with normal to moderately impaired glucose tolerance, and therefore may be useful in population surveys where prolonged, multiple blood sampling test procedures are not possible.
Staphylococcal Septicaemia Complicating Intracavernosal Autoinjection Therapy for Impotence in a Man with Diabetes
Authors: Parfitt V.J. , Wong R. , Dobbie A. , Hartog M. , Gingell J.C.
Published: July 2009

Intracavernosal injection of vasoactive drugs is a safe, effective, and commonly used treatment for impotence in diabetic men. In prospective studies infection has rarely occurred. We report a case of life‐threatening Staphylococcal septicaemia complicating this treatment in a 61‐year‐old man with Type 2 diabetes, probably due to a combination of an unsterile technique and drug‐induced priapism. Infection is a potential risk in diabetic men using intracavernosal injection therapy and those offered it should be informed of the importance of a scrupulous sterile technique and the need to seek urgent medical help for decompression if an erection persists for more than 4–6 h.
Measuring the Albumin Excretion Rate: Agreement Between Methods and Biological Variability
Authors: Cundy T.F. , Nixon D. , Berkahn L. , Baker J.
Published: July 2009

A timed urine collection is necessary to determine the excretion rate of albumin (AER) but such specimens are tedious to collect and frequently inaccurate. Albumin excretion can also be quantified by the use of the albumin:creatinine ratio in randomly obtained specimens. In the present study the agreement between AER as measured on a 24‐h urine collection and as estimated from the albumin:creatinine ratio is determined. Previously published studies have examined the correlation rather than the agreement between these methods and not taken into account the biological variability of AER. Thirty patients with diabetes who had normal renal function, but varying degrees of albuminuria, produced two 24‐h specimens and two random daytime specimens of urine. AER was measured on the former and estimated from the latter by multiplying the albumin:creatinine ratio by an estimate of that individual's creatinine excretion rate. Agreement between the methods and the biological variability was determined by using appropriate statistical methodology, the main outcome measure being the limits of agreement between repeat values for both measurements and both estimates of AER, and between the averages of the measurements and the estimates. The limits of agreement between repeated 24‐h measurements were wide, the second specimen being 33 to 490% of the first. The estimates of AER gave values numerically similar to the measurements. The limits of agreement between the two estimates did not differ significantly from those of the measurements, nor did the limits of agreement when the average of the measurements and the average of the estimates were compared (all NS). The regression line fitted to the plot of the average of the measurements against the average of the estimates did not differ significantly from the line of identity. AER shows considerable biological variability when measured on 24‐h collections. The estimate of AER based on the albumin:creatinine ratio gives numerically equivalent values with a similar degree of variability. The imprecision of this method is clinically irrelevant compared with the magnitude of the biological variability. Determining AER in this way obviates the need for timed urine collections.
Neuropsychological Performance Differs Between Type 1 Diabetic and Normal Men During Insulin‐induced Hypoglycaemia
Authors: Wirsén A. , Tallroth G. , Lindgren M. , Agardh Carl‐David
Published: July 2009

Cerebral function was measured with a neuropsychological test battery before, during, and after insulin‐induced hypoglycaemia (blood glucose approximately 2.0 mmol l−1) in 10 male Type 1 diabetic patients (age 20–43 years, duration of diabetes 14 (2–30) years) and in 12 normal men. There were no group differences in neuropsychological results at normal glucose levels. Significant effects of hypoglycaemia were found in reaction‐time measures (p <0.001) and in other tests requiring speed and attention (p <0.001), in verbal fluency (p <0.05), and short‐term memory (p <0.001). Significant group effects and interactions (p <0.05) revealed that the diabetic patients were generally more affected by hypoglycaemia than the normal subjects. This might have been partly due to the larger absolute decrease in blood glucose level in the diabetic patients, although the rate of glucose decrease was not related to performance in either group. Thus, the diabetic brain might be more vulnerable to hypoglycaemia, perhaps through the persistent impact of repeated hypoglycaemic episodes, although no neuropsychological deficit is demonstrable at normal blood glucose levels.
Diabetic Diets and Nutritional Recommendations: What Happens in Real Life?
Authors: Close E.J. , Wiles P.G. , Lockton J.A. , Walmsley D. , Oldham J. , Wales J.K.
Published: July 2009

Prospective 7‐day estimated weight food records were computer analysed in 92 diabetic patients, 45 men and 47 women, 25 with Type 1 and 67 Type 2 diabetes, attending a hospital‐based diabetic clinic. The nutrient intakes were compared with a national survey in non‐diabetic British adults (OPCS) and the current EASD recommendations for the diabetic diet. Only three diabetic patients achieved the recommended 50–60% energy intake as carbohydrate, four achieved < 30% energy as fat, one patient < 10% saturated fat and 20 ate > 30 g fibre per day. The overall nutrient intakes of these diabetic patients reflected those of non‐diabetic subjects except for a greater intake of protein and smaller intakes of sugar and alcohol. These findings reinforce the problems currently faced in achieving the present recommendations for the diabetic diet.
British Diabetic Association's Discussion Paper on the Role of ‘Diabetic’ Foods
Authors: Thomas B. J. ,   The Nutrition Subcommittee of the British Diabetic Association's Professional Advisory Committee
Published: July 2009

1. Most diabetic foods provide slightly, but not substantially, less energy than comparable non‐diabetic products. 2. Many diabetic foods have a higher fat content than their non‐diabetic equivalents. This is contrary to the requirements of the 1984 Food Labelling Regulations. 3. Many diabetic products have a relatively high content of protein. 4. In percentage terms, the greatest difference between diabetic and non‐diabetic foods remains that of carbohydrate content, particularly carbohydrate other than fructose or sorbitol. On a per portion basis (for instance, per teaspoon of jam) the difference is relatively small and likely to be of minimal practical significance. 5. Diabetic foods cost between 1.5 and 4 times as much as their non‐diabetic equivalents. 6. Some ordinary reduced‐sugar/low calorie products are preferable to diabetic products in terms of fat and energy content and cost. 7. The promotion and widespread availability of diabetic foods tend to delude patients into believing that these products are advantageous, or even necessary. Their existence also undermines current dietary teaching by implying that people with diabetes cannot eat normal foods. 8. Diabetic foods offer no significant physiological or psychological benefits to diabetic patients and can even be counterproductive to good diabetic control. There is no longer a need for special diabetic foods in the modern dietary management of diabetes.
The Distribution and Severity of Diabetic Foot Disease: a Community Study with Comparison to a Non‐diabetic Group
Authors: Walters D.P. , Catling W. , Mullee M.A. , Hill R.D.
Published: July 2009

A surveillance programme was undertaken to identify all diabetic patients with foot disease in a defined population with the same age and sex structure as that of the UK. Of 1150 diabetic patients identified, 1077 were reviewed either at home or in hospital. The presence of foot deformity, amputation, and foot ulceration was determined. The site, depth, and duration of ulcers were recorded and any previous ulceration noted. All feet with ulcers were X‐rayed. A non‐diabetic comparison group of 480 age‐ and sex‐matched individuals were also examined by the same observer. The prevalence of past or present foot ulceration was 7.4 (95% CI 5.8–9.0)% in diabetic patients and 2.5 (95% CI 1.1–3.9)% in the non‐diabetic group, yielding an odds ratio of 2.94 (95% CI 1.58–5.48) (p < 0.001) for the occurrence of foot ulceration in diabetic patients. Of the ulcers found on examination, 39.4% were neuropathic, 24.2% were vascular, and 36.4% were mixed. Multiple logistic regression analysis of selected variables revealed that duration of diabetes, absent light touch, impaired pain perception, absent dorsalis pedis pulse, and the presence of any retinopathy were significant predictors of the presence of foot ulcers. The prevalence of amputation in diabetic patients was 1.3 (95% CI 0.6–2.0)%, but there were no amputations in the non‐diabetic group.
Can Life‐styles of Subjects With Impaired Glucose Tolerance Be Changed? A Feasibility Study
Authors: Page R.C.L. , Harnden K.E. , Cook J.T.E. , Turner R.C.
Published: July 2009

Thirty‐one subjects with impaired glucose tolerance were randomly allocated to a group receiving advice to improve their diet and physical activity levels over 6 months (n = 23) or to a control group (n = 8). At 6 months, 18 of the 23 subjects receiving ‘healthy living’ advice were re‐examined (five subjects had withdrawn). Fourteen of the 18 subjects showed an alteration in diet or an increase in exercise. The 18 subjects re‐evaluated showed a reduction in systolic blood pressure (118 ± 15 vs 124 ± 15 mmHg, p < 0.05) and decrease in total plasma cholesterol (4.5 ± 1 vs 5.2 ± 1 mmol I−1, p < 0.01) and LDL‐cholesterol levels (2.8 ± 0.9 vs 3.2 ± 0.9 mmol I−1, p < 0.05). Plasma glucose levels were unchanged. One subject withdrew from the control group. At 6 months, the seven control subjects examined showed no significant change in metabolic parameters, with little measurable change in diet or exercise. At 2 years, 17 of the 23 ‘healthy living’ subjects were reassessed. Nine of the subjects had continued to exercise or maintained a decreased weight compared to baseline. Fasting plasma glucose levels had increased (6.0 ± 1.2 vs 5.5 ± 0.6 mmol I−1, p < 0.05) with the only continued improvement being a reduced LDL level (2.8 ± 0.7 vs 3.1 ± 0.9 mmol I−1, p < 0.05). At 2 years, a similar proportion of the control group were taking regular exercise compared with the ‘healthy living’ group. In conclusion, a 6‐month training programme altered diet and exercise patterns with beneficial effects on blood pressure and plasma lipid levels, but except for LDL cholesterol these changes were not maintained once support was withdrawn.
Peripheral Glucose Uptake and Skeletal Muscle GLUT4 Content in Man: Effect of Insulin and Free Fatty Acids
Authors: Handberg Aa. , Vaag A. , Beck‐Nielsen H. , Vinten J.
Published: July 2009

To investigate the relationship between glucose uptake and the content of the insulin regulatable glucose transporter, GLUT4, in skeletal muscle at near physiological insulin concentrations in vivo, we measured the effect of a 3h euglycemic insulin‐infusion (40 mU m−2 min−1) on glucose uptake and skeletal muscle GLUT4 content in 10 healthy subjects. We found no correlation (r ≅ 0.1) between individual muscle GLUT4 content and insulin‐stimulated glucose uptake. Mean GLUT4 content in skeletal muscle was reduced by 19 ± 6.3% (mean ± SE, p < 0.02) after insulin infusion. However, when the same subjects were made insulin resistant by infusion of lipid, as evidenced by a reduction of 16 ± 7.2% (mean ± SE, p < 0.05), in insulin‐stimulated glucose uptake, the effect of insulin on GLUT4 content was attenuated and no change in GLUT4 content was observed. Our results show that the total content of skeletal muscle GLUT4 is a poor predictor for in vivo response to near physiological insulin concentrations in healthy human subjects.