bluuebunny/crossref_metadata_2025 huggingface dataset:
The Regulation of Post‐prandial Cellular Cholesterol Metabolism in Type 2 Diabetic and Non‐diabetic Subjects
Authors: Stinson J.C. , Owens D. , McBrinn S. , Collins P. , Johnson A. , Tomkin G.H.
Published: July 2009

The purpose of the study was to determine the effect of diabetes on the regulation of postprandial cholesterol metabolism. Four groups of patients (n = 8 for each group) were examined: Type 2 diabetic patients with and without hypercholesterolemia and nondiabetic subjects with and without hypercholesterolaemia. Serum lipoproteins, lipoprotein composition, cellular cholesterol, and cellular cholesterol synthesis were measured before and 4 h after a high calorie meal. The BMI for the hypercholesterolaemic diabetic patients of 31.5 ± 0.95 (SEM) was significantly higher than that for the control group of 26.2 ± 1.0 (p < 0.01). Fasting triglyceride levels were significantly higher in the normocholesterolaemic and hypercholesterolaemic diabetic patients and in the hypercholesterolaemic non‐diabetic subjects (1.45 ± 0.22, 2.27 ± 0.34, and 1.58 ± 0.18 mmol l−1, respectively) compared with normocholesterolaemic non‐diabetic subjects (0.75 ± 0.12 mmol l−1: p < 0.01). The normocholesterolaemic and hypercholesterolaemic diabetic subjects had significantly lower fasting serum high density lipoprotein (HDL) (1.06 ± 0.08 and 1.04 ± 0.06 mmol l−1) compared to the corresponding non‐diabetic groups (1.29 ± 0.11 and 1.45 ± 0.17 mmol l−1, p < 0.05). The esterified/free cholesterol ratio of very low density lipoprotein (including chylomicrons VLDL‐C) decreased postprandially in all groups with an overall decrease of 1.33 to 0.83 (p < 0.01). Fasting cellular cholesterol in mononuclear leucocytes from normocholesterolaemic diabetic patients was similar to that for hypercholesterolaemic diabetic (36.8 ± 1.2 vs 40.6 ± 5.5 mg g−1 protein) and non‐diabetic subjects (36.7 ± 6.8 mg g−1 protein) and significantly greater than cholesterol in cells from control subjects (29.7 ± 1.5 mg g−1 protein, p < 0.05). In cells from control subjects only, there was a significant postprandial increase in cholesterol to 39.4 ± 5.2 mg g−1 protein (p < 0.05) and a corresponding postprandial reduction in cholesterol synthesis from 149 ± 34 to 102 ± 33 nmol g−1 cell protein (p < 0.05). These results demonstrate a lack of correlation between serum and cellular cholesterol in diabetic patients and an inability to suppress cellular cholesterol synthesis postprandially in these patients. The differences may, in part, explain the increased deposition of cholesterol in atheromatous plaques in normocholesterolaemic diabetic patients.
Improved Blood Glucose Control by Insulin Therapy in Type 2 Diabetic Patients Has No Effect on Lipoprotein(a) Levels
Authors: Wolffenbuttel B.H.R. , Leurs P.B. , Sels J.P.J.E. , Rondas‐Colbers G.J.W.M. , Menheere P.P.C.A. , Kruseman A.C. Nieuwenhuijzen
Published: July 2009

The effects of improved blood glucose control by insulin therapy on lipoprotein(a) and other lipoproteins were studied in 54 patients with Type 2 diabetes (mean ± SD: age 67 ± 9 years, body mass index 26.1 ± 4.4 kg m−2, median duration of diabetes 10 (range 1–37) years, 23 males, 31 females), who were poorly controlled despite diet and maximal doses of oral hypoglycaemic agents. After 6 months of insulin treatment, mean fasting blood glucose concentrations had decreased from 14.1 ± 2.2 mmol l−1 to 8.4 ± 1.8 mmol l−1 (p < 0.001), and HbA1c had fallen from 11.1 ± 1.4 % to 8.2 ± 1.1 % (p < 0.001). Significant decreases of total and LDL cholesterol, triglycerides, apolipoprotein B, and free fatty acids were observed, while HDL‐cholesterol and apoA1 increased by 10 %. Baseline serum Lp(a) levels were elevated compared to non‐diabetic subjects of similar age (median 283, range 8–3050 mg I−1, vs 101, range 8–1747 mg I−1, p < 0.05), but did not change with insulin, and there was no correlation with the degree of metabolic improvement and changes in Lp(a) levels. It is concluded that improved blood glucose control by insulin therapy does not alter elevated Lp(a) levels in Type 2 diabetic patients, but has favourable effects on the other lipoproteins.
Fetal Outcome in Mothers with Impaired Glucose Tolerance in Pregnancy
Authors: Roberts R.N. , Moohan J.M. , Foo R.L.K. , Harley J.M.G. , Traub A.I. , Hadden D.R.
Published: July 2009

A 75 g oral glucose tolerance test was carried out on 953 pregnant women who were identified on the basis of clinical risk factors. The tests were analysed by the WHO criteria: 826 were normal, 120 showed impaired glucose tolerance, and 7 identified diabetes. A number of obstetric and perinatal outcome measures were compared between the groups with normal and impaired glucose tolerance, and also with 135 women who had pre‐existing Type 1 diabetes and delivered during the study period. There was no significant difference in the incidence of antenatal complications between mothers with normal and impaired glucose tolerance. There was a higher rate of induced labour (p < 0.05) and caesarean section (p < 0.01) in the impaired glucose tolerance group compared to the normal group, but no difference in fetal outcome or neonatal morbidity. All of these outcome measures were increased in the Type 1 diabetic pregnancies.
Segmental Tubular Sodium Reabsorption in Type 1 Diabetes
Authors: Dieperink H. , Eshøj O. , Leyssac P.P. , Feldt‐Rasmussen B.
Published: July 2009

Segmental tubular sodium reabsorption in Type 1 (insulin‐dependent) diabetes was measured in 36 patients in a cross‐sectional study including one group (n = 13) without significant albuminuria (UalbV < 30 mg 24 h−1), one group (n = 16) with albuminuria in the range from 30 to 300 mg 24 h−1, and a group (n = 7) with nephropathy (UalbV > 300 mg 24 h−1). Lithium clearance was used to measure end proximal delivery. From end proximal delivery, 51Cr‐EDTA clearance (GFR) and sodium clearance, segmental tubular reabsorption was calculated. For all patients, GFR was directly correlated with end proximal delivery (r = 0.62, p<0.0005), while end proximal delivery was inversely correlated to fractional proximal reabsorption (r = −0.71, p<0.0005). In the subgroup with UalbV less than 30 mg 24 h−1, the direct correlation between GFR and end proximal delivery was also significant (r = 0.77, p<0.05). In the group with nephropathy (UalbV > 300 mg 24 h−1), mean GFR and end proximal delivery were decreased and fractional proximal reabsorption was increased, but there was still a positive correlation between GFR and end proximal delivery (r = 0.75, p<0.05) and an inverse correlation between end proximal delivery and fractional proximal reabsorption (r = −0.85, p<0.05). It is concluded that in these groups of diabetic patients the end proximal delivery is increased while GFR is increased. This finding is an argument against a recent hypothesis explaining intraglomerular hypertension, as well as increased glomerular filtration rate in some patients, as secondary to decreased end proximal delivery and reduced tubuloglomerular feedback activity. Nevertheless, the tubuloglomerular feedback activity may be reduced in Type 1 diabetes due to constant extracellular volume expansion.
Indomethacin But Not Metoprolol Reduces Exercise‐induced Albumin Excretion Rate in Type 1 Diabetic Patients with Microalbuminuria
Authors: Rudberg S. , Sätterström G. , Dahlqvist R. , Dahlquist G.
Published: July 2009

The effects of a single oral dose of indomethacin (1 mg kg−1), metoprolol (1.5 mg kg−1) and placebo on exercise‐induced albumin excretion rate (AER) were compared in a randomized, crossover design in 14 normotensive, young Type 1 diabetes patients, nine of them with microalbuminuria (AER > 15 μg min−1) and five without microalbuminuria at rest. The albumin excretion rate, blood pressure, heart rate, blood glucose, and plasma concentrations of indomethacin and metoprolol were determined before and after 30 min submaximal physical exercise. In microalbuminuric patients the rise in albumin excretion rate after exercise on indomethacin (7 μg min−1) was lower than after placebo (29 μg min−1, p < 0.001) whereas the rise in albumin excretion rate with metoprolol during exercise (18 μg min−1) did not differ from placebo (p = 0.48), in spite of the expected less marked increase in blood pressure. In normoalbuminuric patients no significant increase in albumin excretion rate was noted by exercise in any of the treatment periods. A tendency to a linear correlation (r = −0.54, p = 0.07) was seen between the plasma concentration of indomethacin and the inhibition of exercise‐induced increase in albumin excretion rate. No correlations were observed between exercise‐induced changes in albumin excretion rate and systolic blood pressure, heart rate or blood glucose. In conclusion, acute indomethacin treatment, presumably through inhibition of renal prostaglandin synthesis, reduces the exercise‐induced rise in albumin excretion rate in Type 1 diabetic patients with microalbuminuria. Such an effect was not seen after acute administration for the beta‐1‐adrenoceptor blocking drug metoprolol, in spite of a less marked rise in blood pressure.
The Scanning Laser Ophthalmoscope and Retinal Assessment in Diabetes
Authors: Pope R.M. , King A. , Geall M. , Martin B.M.
Published: July 2009

In order to evaluate the Scanning Laser Ophthalmoscope as a method of assessing diabetic retinopathy, 57 consecutive patients with diabetes were examined through undilated pupils using laser ophthalmoscopy followed by pupillary dilatation and direct ophthalmoscopy. Results of laser scanning were recorded on videotape and analysed independently. Scanning (both eyes) took under 5 minutes per patient. For the 113 eyes studied, the two techniques gave concordant results in 73/113 (65%). Where there was discordance, laser ophthalmoscopic severity was greater than direct ophthalmoscopy in 36/40 (90% of discordant results). In 4/40 eyes conventional ophthalmoscopic appearances were judged more severe than those seen with the laser. The laser ophthalmoscope may have value as a method of assessing diabetic retinopathy, but further work is required to evaluate its efficacy as a screening tool in patients with moderate to severe retinopathy.
No Pharmacokinetic Effect of Retaining the Infusion Site up to Four Days During Continuous Subcutaneous Insulin Infusion Therapy
Authors: Olsson P.O. , Arnqvist H. , Asplund J.
Published: July 2009

This study was designed to investigate whether the indwelling time of the needle during continuous subcutaneous insulin infusion (CSII) could contribute to one of the main problems with subcutaneous insulin administration, that is the day‐to‐day intra‐patient variation in absorption. The effect on insulin kinetics after a bolus dose was investigated at different time intervals up to 4 days after insertion of an indwelling catheter in situ for CSII therapy. Nine insulin‐dependent diabetic patients treated with pump (Nordisk Infuser; Velosulin 100 U ml−1) took part in the study. The evening before day 1 of the investigation a needle connected to the pump with a polyethylene catheter was inserted subcutaneously on the abdominal wall where it remained throughout the investigation. There were no significant differences in blood glucose or plasma free insulin profiles between days 1, 3, and 5. The intra‐patient coefficient of variation of free insulin was 38% at basal and 19% at post‐bolus state. We conclude that during CSII it is acceptable from a pharmacokinetic point of view to retain the infusion site for up to 4 days.
BOOK REVIEWS
Authors: Sills M.A.
Published: July 2009

Book reviewed in this article:

Epidemiology and Etiology of Insulin‐Dependent Diabetes in the Young. Edited by C. Levy‐Marchal and P. Czernichow
The Prevalence of Type 1 Diabetes Mellitus at Follow‐up of Swedish Infants Congenitally Infected with Cytomegalovirus
Authors: Ivarsson S.‐A. , Lindberg B. , Nilsson K.O. , Ahlfors K. , Svanberg L.
Published: July 2009

In a Swedish prospective study of congenital cytomegalovirus (CMV) infection, 76 infants were shown to be infected among 16474 newborns screened by virus isolation in urine. Seventy‐three of the excreters were followed up and one developed Type 1 diabetes, as compared to 38 of the 19483 children born during the same period (p = 0.14, Fisher's one‐tailed test). Thus we found no evidence that the combined finding of congenital CMV infection and Type 1 diabetes mellitus was related.
Psychological Factors and their Relationship to Diabetes Control
Authors: Gordon D. , Fisher S.G. , Wilson M. , Fergus E. , Paterson K.R. , Semple C.G.
Published: July 2009

Thirty‐nine Type 1 diabetic patients were asked to complete an Eysenck Personality Questionnaire (EPQ). A significant relationship was found between neuroticism scores and glycosylated haemoglobin concentrations (r = 0.43, p < 0.01) and also fructosamine (r = 0.45, p < 0.01). Patients with glycosylated haemoglobin concentrations greater than or equal to 10 (n = 13) had significantly higher neuroticism scores than patients with glycosylated haemoglobin results less than or equal to 8 (n = 11) (p < 0.01).
Accurate and Precise Blood Glucose Measurement in the Hypoglycaemic Range
Authors: Tieszen K.L. , Patrick A.W. , Smith E. , Williams G. , Dornan T.L.
Published: July 2009

The aim of the study was to evaluate the performance of an electrochemical blood glucose sensor, the satellite G, in the low‐normal and hypoglycaemic range. Eighty‐five venous blood samples with glucose concentrations below 4.0 mmol l−1 from six patients with Type 1 diabetes undergoing induced hypoglycaemia were measured in duplicate on the sensor and a reference method, the Yellow Springs whole blood glucose analyser. The sensor values correlated well with the reference method (r = 0.9, p < 0.001) with a mean absolute percentage bias of 10.7%. The 95% confidence limits of agreement between methods were +0.7 and −0.6 mmol l−1 with a mean difference of 0.04 mmol l−1. More than 80 % of the sensor measurements were within 20 %, and 60 % were within 10 % of the reference method. Measured over all samples, the sensor had a coefficient of variation of 7.2 % for paired measurements. The coefficients of variation of 20 measurements on each of two samples with glucose concentrations of 1.3 and 2.6 mmol l−1 were 9.1 % and 5.8 %, respectively. We conclude that the satellite G measures blood glucose accurately and precisely in the low range.
Glycated Haemoglobin Centiles: A Basis for Audit in Children's Clinics?
Authors: Wales J.K.H. , Forrest A.R.W.
Published: July 2009

Services for children with diabetes are a good model for audit because of relatively well‐defined and available measures of outcome. Estimation of glycated haemoglobin (HbA1) is accepted as one index of control, although the assay and normal ranges vary in different centres. Sheffield has a stable clinic population and we have taken blood for HbA1 on each patient two to four times per year since 1983. HbA1 values have been aligned in 3‐monthly increments from time of diagnosis to construct a graph showing the mean plus or minus two standard deviation values for the clinic population and also a rough ‘centile chart’ that describes the unfortunate but expected pattern of deteriorating control with duration of diabetes. There are undoubtedly methodological flaws in this novel approach; however, such charts constructed for each clinic may be a suitable basis for comparative assessment of the control of an individual and also for auditing the effects of changes in practice that strive for optimum glucose levels in the clinic population.
Potential Therapeutic Approaches to the Treatment or Prevention of Diabetic Neuropathy: Evidence from Experimental Studies
Authors: Cameron N.E. , Cotter M.A.
Published: July 2009

Recent investigations using experimental models of diabetes mellitus have emphasized the importance of impaired blood flow for the development of nerve dysfunction. Other observations suggest that this may also be the case for patients. A number of studies have revealed that several types of vasodilators can prevent or successfully treat early conduction abnormalities in diabetic rodents. These include α1‐adrenoreceptor antagonists, calcium channel blockers, agents that inhibit the renin‐angiotensin system, and vasomodulator prostanoids. Other treatments applied to animal models, such as w‐6 essential fatty acids, aldose reductase inhibitors, aminoguanidine which prevents the formation of advanced glycation end‐products, and anti‐oxidants all appear to have vascular‐related effects that lead to improvements in nerve conduction. These findings suggest that endothelial dysfunction and oxidative stress could be important factors in the aetiology of diabetic neuropathy. Studies have also focused on deficits in axon growth and regeneration, their relation to impaired neuronal synthesis and transport of growth‐related chemicals, and neuronotrophic abnormalities. Taken together, the data give rise to the notion that an optimal therapeutic strategy could consist of improving the microenvironment of damaged nerve fibres by manipulating nerve blood flow while concurrently encouraging repair with trophic agents.
Sensori‐motor Function in Older Persons with Diabetes
Authors: Lord S.R. , Caplan G.A. , Colagiuri R. , Colagiuri S. , Ward J.A.
Published: July 2009

Twenty‐five persons with diabetes (aged 55–83 years) who were living independently in the community, and 40 age‐ and sex‐matched non‐diabetic controls were assessed for tactile sensitivity, vibration sense, proprioception, quadriceps strength and body sway. In both men and women, those with diabetes performed significantly worse in tests of body sway on firm and compliant surfaces compared with the control subjects after controlling for weight and body mass index. The female diabetic subjects also performed significantly worse in tests of peripheral sensation and strength compared with controls. Age‐related declines in sensori‐motor function were greater in the diabetic group (r = 0.55–0.75) than in the controls (r < 0.44), while within the diabetic group, duration of diabetes and vibration sense were significantly correlated with sway on a compliant (foam rubber) surface with the eyes open (partial r = 0.52, p < 0.01 and r = 0.55, p < 0.01, respectively). The study findings provide evidence that older people with diabetes have problems with stability and related sensori‐motor factors which may place them at increased risk of falls.
The Acute Effect of Preprandial Exogenous and Endogenous Sulphonylurea‐stimulated Insulin Secretion on Postprandial Glucose Excursions in Patients with Type 2 Diabetes
Authors: Groop P.‐H. , Melander A. , Groop L.C.
Published: July 2009

Sulphonylureas improve glucose tolerance by stimulating insulin secretion. Whether improved glucose tolerance results from enhanced early insulin release or greater total insulin secretion is not clear. Insulin responses to a test meal in Type 2 diabetic subjects with and without a single dose (2.5 mg) of oral and intravenous glipizide were, therefore, measured. Intravenous glipizide enhanced early insulin release more than oral glipizide (134% and 80% vs control; p<0.01), whereas total insulin release was equally improved (78% and 54% vs control; p<0.01). Despite slight differences in insulin release, there was no difference in glucose tolerance (median area under concentration curve (AUC); 66.6 vs 61.9 mmol × min I−1; NS). The test meal was repeated after a bolus of intravenous insulin at the beginning of the meal. This allowed comparison of the effect of exogenous and endogenous insulin supply on postprandial glucose excursions. In spite of an early and fivefold larger rise in serum insulin after intravenous administration of the hormone than after intravenous glipizide (725% vs 134%; p<0.01), postprandial glucose was no better than after glipizide (median AUC; 87.8 vs 66.6 mmol × min I−1; NS). In contrast, glucose tolerance was better after oral glipizide compared to intravenous insulin (median AUC; 61.9 vs 87.8 mmol × min I−1; p<0.05). In conclusion, the total amount of insulin secreted seems more important than the timing of the insulin release for the postprandial glucose tolerance in Type 2 diabetic subjects. Neither endogenous nor peripheral pre‐meal supply of insulin could normalize postprandial glucose excursions in patients with Type 2 diabetes.
The Relationship Between Plasminogen Activator Inhibitor‐1 and Insulin Resistance in Newly Diagnosed Type 2 Diabetes Mellitus
Authors: Gough S.C.L. , Rice P.J.S. , McCormack L. , Chapman C. , Grant P.J.
Published: July 2009

It is not clear whether elevated levels of the fibrinolytic inhibitor, plasminogen activator inhibitor‐1 (PAI‐1) in Type 2 diabetes mellitus are the result of obesity or coexistent atherosclerosis. Therefore the relationship between PAI‐1 and insulin resistance, determined by the homeostasis model assessment (HOMA) was investigated in a group of 26 insulin‐resistant, normotensive newly diagnosed Type 2 diabetic patients with a low probability of atherosclerosis. Compared with a normal control group, closely matched for body mass index (BMI), fibrinolytic activity was depressed in the diabetic patients due to elevated levels of the inhibitor PAI‐1, 17.6 (11.1–28) vs 8.4 (4.9–14.1) IU ml−1, p < 0.001. PAI‐1 was related to BMI, r = 0.59, p < 0.001 plasma insulin, r=0.66, p < 0.001; insulin resistance, r = 0.54, p< 0.005 and urinary albumin excretion, r=0.48, p < 0.01, but not HbA1c or fasting glucose. PAI‐1 was not related to blood pressure or plasma triglyceride levels. This study suggests that at the time of diagnosis of Type 2 diabetes mellitus, elevated PAI‐1 levels are already linked to other risk factors for vascular disease including hyperinsulinaemia, insulin resistance, and urinary albumin excretion, and this is not the result of obesity or coexistent atherosclerosis.
Altered Regulation of Cholesterol Metabolism in Type I Diabetic Women During the Menstrual Cycle
Authors: Owens D. , Cox M. , Caird J. , Gilligan S. , Collins P. , Johnson A. , Tomkin G.H.
Published: July 2009

This study examines the relationship of cellular cholesterol metabolism to oestrogen and progesterone during the menstrual cycle in diabetic and non‐diabetic subjects. Nine premenopausal diabetic women were compared to nine non‐diabetic women of the same age. Oestrogen, progesterone, lipoproteins, including lipoprotein (a) (Lp(a)) and cholesteryl ester transfer protein (CETP) were determined in serum. Cellular cholesterol content and cellular cholesterol synthesis were measured in mononuclear leucocytes. There was no significant change in serum lipoproteins including Lp(a) during the cycle in either group. CETP activity was significantly higher over the 4 weeks in the diabetic patients compared with non‐diabetic subjects (mean 463 ± μmol I***−1 h−1 vs 405 ± 28 μmol ***I−1 h−1, p<0.01). Serum high density lipoprotein (HDL) cholesterol was significantly lower during the 4 weeks in the diabetic patients (1.7 ± 0.1 mmol I−1 vs 1.8 ± 0.1 mmol−1, p<0.05). Cellular cholesterol synthesis decreased steadily up to the third week in cells from the control subjects whereas there was no significant change in cells from diabetic patients whose cellular cholesterol synthesis was higher at week 3 compared with non‐diabetic subjects (663 ± 54 nmol mg−1 cell protein vs 432 ± 43 nmol mg−1 cell protein, two‐way interaction p<0.05). There was a significant negative correlation between cellular cholesterol synthesis and serum oestrogen in the non‐diabetic subjects (p<0.05) but not in the diabetic patients. These results show that cellular cholesterol synthesis is not downregulated during the menstrual cycle in diabetic patients, a finding which may help to explain the increased incidence of atherosclerosis in the diabetic, pre‐menopausal woman.
Hypoglycaemia Increases the Gastric Emptying Rate in Patients with Type 1 Diabetes Mellitus
Authors: Schvarcz E. , Palmér M. , Åman J. , Lindkvist B. , Beckman K.‐W.
Published: July 2009

The effect of insulin‐induced hypoglycaemia on the gastric emptying rate was studied in eight patients with Type 1 diabetes mellitus of short duration (1–5 years). Gastric emptying was studied using a scintigraphic technique. All patients were studied twice, both during euglycaemia and insulin‐induced hypoglycaemia. The blood glucose concentration was adjusted with an insulin‐glucose clamp technique. All patients were examined in a standardized way, undergoing the first examination during euglycaemia, with a blood glucose concentration of 4–7 mmol ***I−1, and the second during hypoglycaemia, with a mean blood glucose concentration of 1.9 ± 0.3 mmol ***I−1 at the time of starting the gastric emptying study. During hypoglycaemia both the liquid and the solid gastric emptying rates were significantly increased compared to the rate during euglycaemia. The time to empty 50% of the radioactivity from the stomach for liquid was 48.5 ± 9.8 min during euglycaemia, compared to 27.6 ± 20.2 min during hypoglycaemia, p < 0.001. The time to empty 50% of the radioactivity from the stomach for solid food was 48.7 ± 10.3 min and 23.2 ± 15.9 min, respectively, p < 0.001. In conclusion, it appears that insulin‐induced hypoglycaemia increases the gastric emptying rate in patients with Type 1 diabetes mellitus.
Autonomic and Peripheral Nerve Function in Adolescents With and Without Diabetes
Authors: Donaghue K.C. , Bonney M. , Simpson J.M. , Schwingshandl J. , Fung A.T.W. , Howard N.J. , Silinka M.
Published: July 2009

In this study reference ranges were established for autonomic and peripheral nerve tests in 122 non‐diabetic adolescents. Regression analysis was used to evaluate the effect of age and gender on neurological function. Increasing age was associated with: less heart rate variability during deep breathing (p = 0.03), higher thermal threshold for cold at the wrist (p = 0.009), and higher vibration threshold at the toe (p = 0.001) and medial malleolus (p = 0.01). Male gender was associated with higher Valsalva ratio (p = 0.0004), higher thermal threshold for hot at the foot (p = 0.002), and higher vibration threshold at the malleolus (p = 0.03). The REFVAL programme was used to determine parametric or non‐parametric reference limits: the 5% limits for autonomic and 95% limits for peripheral tests. One hundred and eighty‐one adolescents with diabetes were studied under identical conditions and similar effects of age and gender were found. Twenty‐eight percent of the group with diabetes had at least one abnormal autonomic test result out of four (expected 18.5%); 24% had at least one abnormal peripheral test result out of six (expected 26.5%). Glycaemic control was associated with autonomic (p = 0.04) but not peripheral abnormalities. Using multiple regression analysis and adjusting for age and gender, there was no effect of diabetes duration or glycaemic control on neurological function.
The Effectiveness of a Primary‐Care‐Based Diabetes Education Service
Authors: Redhead J. , Hussain A. , Gedling P. , McCulloch A.J.
Published: July 2009

The efficacy of structured education for 158 Type 2 diabetic patients in primary care (80 male, mean age 63 yr, median diabetes duration 3 yr) was assessed with respect to change in knowledge of diabetes, weight, and haemoglobin A1, over a 6‐month period. The programme supplemented a primary care initiative in our semi‐rural population. Teaching was carried out by a Diabetes Nurse Educator within primary care health centres (141 patients) and a hospital diabetes clinic (17 patients). For all patients mean baseline questionnaire score (maximum possible 12) was 6.2 rising after the programme to 10.5 (p < 0.01). At 6 months mean score fell to 9.5 (p < 0.01 compared to end of the programme), but still significantly better than baseline (p<0.01). For patients on the primary‐care‐based programme mean haemoglobin A1 at baseline was 10.7% (normal range 6%–9%) decreasing after 6 months to 9.6% (p < 0.01). No significant changes were found in mean weight. Unlike many previous studies, these results demonstrate a highly beneficial effect not only on knowledge but also on metabolic control in patients who received their education in the primary‐care setting. These results have obvious implications for patients residing in rural or semi‐rural populations.
The Description and Classification of Diabetic Foot Lesions
Authors: Jeffcoate W.J. , Macfarlane R.M. , Fletcher E.M.
Published: July 2009

Diabetic foot ulcers are of many types and different ulcers require management in different ways. Their optimal management is currently hindered by lack of a useful working classification. Such a classification must be flexible enough to be applied to all lesions likely to be encountered but specific enough to enable clear definition of an individual lesion. It must also be simple enough to ensure that it is understood by all categories of health care workers, whether specialist or not. An attempt has been made to devise a classification—based on the key elements used in describing foot lesions—and it is put forward to act as stimulus for debate. It is based on the clinical definition of infection, ischaemia, and neuropathy. Although two of these, or even all three, may be found in the same foot, they should be considered in the order given because this reflects the sequence of clinical decisions which should be made. The adoption of a classification such as this would aid education, communication, research and audit, and would lead to better management of ulcers.
Microsatellite Polymorphisms at the Glucokinase Locus: a Population Association Study in Caucasian Type 2 Diabetic Subjects
Authors: Hattersley A.T. , Saker P.J. , Cook J.T.E. , Stratton I.M. , Patel P. , Permutt M.A. , Turner R.C. , Wainscoat J.S.
Published: July 2009

Glucokinase has a central role in glucose metabolism in pancreatic beta cells and hepatocytes and is an important candidate gene for Type 2 diabetes. Mutations of the glucokinase gene have been reported in Caucasian pedigrees with maturity‐onset diabetes of the young and late‐onset Type 2 diabetes. In population studies of American Blacks and Mauritian Creoles an association between alleles of a glucokinase polymorphism and Type 2 diabetes has been described. Two microsatellite polymorphisms (GCK 1 and GCK 2) flanking the glucokinase gene were investigated in Caucasian subjects. There was no significant linkage disequilibrium between the alleles of the two polymorphisms. The overall allelic frequencies for GCK 1 and the combined haplotypes did not significantly differ between 95 Type 2 diabetic and 76 normoglycaemic subjects. In an expanded cohort of 151 diabetic subjects the allelic frequencies at GCK 2 were also similar to controls. These results suggest that a single mutation of the glucokinase gene is not a common cause of Type 2 diabetes in English Caucasians.
Urinary Excretion and Clearance of Insulin in Diabetic and Normal Children and Adolescents
Authors: Phillips P.E. , Edge J.A. , Harris D.A. , Kay J.D.S. , Tomlinson P. , Hourd P. , Dunger D.B.
Published: July 2009

Seventy‐two diabetic (38 males) and 86 normal (41 males) children provided timed overnight urine collections. Fourteen of the diabetic and 33 of the normal children had concurrent overnight plasma insulin profiles. Urinary insulin clearance in the diabetic subjects was compared with excretion of albumin, growth hormone, retinol‐binding protein, and N‐acetyl‐β‐D‐glucosaminidase. In the normal subjects, urinary insulin excretion correlated with mean overnight plasma levels in the boys (r = 0.82, p< 0.001) but not in the girls (r = 0.32), and varied with puberty stage in the boys. Insulin clearance was greater in boys than girls during puberty, and fell in both sexes with advancing puberty. Insulin excretion was greater in diabetic than normal children in both sexes at all puberty stages. Insulin clearance was also greater in diabetic than normal subjects (1.05 ± 0.1 ml min−1 1.73 m−2 vs o.48 ± 0.05 ml min−1 1.73 m−2, p< 0.001). Insulin excretion as a percentage of the filtered load was also greater in diabetic than normal subjects (1.9 ± 0.27% vs 0.85 ±0.09%, p < 0.01). In the diabetic children, there was a correlation between urinary insulin and growth hormone excretion (r = 0.52, p < 0.02), and retinol‐binding protein in those (n = 10) with higher retinol binding protein excretion (r = 0.76, p = 0.01). The value of urinary insulin excretion as a measure of free plasma insulin levels in normal and diabetic children may be limited by sex differences in renal insulin clearance, and by proximal renal tubular dysfunction in children with diabetes.
Preservation of Renal Haemodynamic Response to an Oral Protein Load in Non‐insulin‐dependent Diabetes Mellitus
Authors: Vora J.P. , Thomas D. , Peters J.R. , Coles G.A. , Williams J.D.
Published: July 2009

Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) were determined, for 2h prior to and 3h following the ingestion of a 1.2 g kg−1 meat meal, in seven normotensive normoalbuminuric Type 2 diabetic patients exhibiting good glycaemic control (fasting plasma glucose (mean ± SD): 7.2 ± 2.0 mmol l−1; glycosylated haemoglobin: 8.1 ± 1.7%) and in nine normal subjects selected for similar basal GFR values. Baseline GFR and ERPF (corrected to 1.73 m2 surface area) were 83 ± 10 and 410 ± 76 ml min−1 for the Type 2 diabetic patients and 86 ± 11 and 405 ± 113 ml min−1 for the normals. GFR increased by 38 ± 8 and 32 ± 15% in the diabetic patients and normals, to 108 ± 25 and 105 ± 26 ml min−1 (p < 0.01 vs baseline). Peak ERPF was 501 ± 127 and 476 ± 119 ml min−1 for the two respective groups (p < 0.01 vs baseline). Filtration fractions at peak GFR and EPRF values were unchanged from baseline for either groups. Fractional clearance of albumin for the Type 2 diabetic patients was unaltered by protein ingestion. Therefore, protein ingestion in Type 2 diabetes, as in normals, results in an acute elevation of GFR. Absolute and incremental changes in GFR were identical for the two groups. These data demonstrate a preserved capacity for renal vasodilatation in Type 2 diabetic patients despite their greater chronological age.
Dermatoglyphics in Type 1 Diabetes Mellitus
Authors: Ziegler A.‐G. , Mathies R. , Ziegelmayer G. , Baumgartl H.‐J. , Rodewald A. , Chopra V. , Standi E.
Published: July 2009

Although fingerprints and handprints are widely used in criminology, it is only recently that this approach has been applied to the field of medical and genetic diagnoses. In order to investigate dermatoglyphics in Type 1 diabetes mellitus, quantitative characteristics of fingers and palms (ridge count and main line indices) as well as qualitative parameters such as digital and interdigital patterns, the position of the palmar axial triradii and main line courses were analysed in 88 male and 108 female Type 1 diabetic patients and compared with data from 100 male and 99 female normal controls. Type 1 diabetic patients show a lower third finger ridge count (p < 0.05) and a‐b ridge count (p < 0.001) and higher transversality of the main lines as indicated by the main line index value (p < 0.001) or the ending of the main line A in a specific sector 5, 5′, and 5′ (p < 0.001) compared with controls. In addition, diabetic patients show higher frequency of palmar axial t' and t' triradii (p < 0.001) and a lower frequency of ‘true’ patterns in the fourth interdigital and thenar area (p < 0.001) than controls. By multivariate analysis of quantitative and qualitative variables a predictive value of 78.6% and 77.3%, respectively, for male, and 81.4% and 82.2%, respectively, for female Type 1 diabetic patients was found. In conclusion, dermatoglyphics seem to be an interesting tool for genetic studies related to Type 1 diabetes.
Application of Physicians' Predictions of Meal and Exercise Effects on Blood Glucose Control to a Computer Simulation
Authors: Hauser T. , Campbell L.V. , Kraegen E.W. , Chisholm D.J.
Published: July 2009

Our aim was to develop a computer simulator program that allows patients to practise insulin dose and dietary adjustment on a day of planned exercise, and shows the resulting blood glucose response in an average diabetic patient. The degree of blood glucose change predicted by the program was determined from changes predicted by five local specialists in seven hypothetical scenarios involving exercise ± dietary or insulin dose adjustments. The program was then tested against 18 outside specialists' responses in 7 different scenarios. The program simulates the 24 h glycaemic response after 45 min mild or moderate exercise starting 2 h after meals, as well as changes to this response induced by alterations in dietary carbohydrate and/or insulin dose. Coefficients of variation of specialists' blood glucose predictions were greater for exercise (35% local, 31% outside specialists) than dietary change (7% local, 10% outside specialists; p = 0.002‐0.04). The program's predicted change in blood glucose levels in the seven scenarios correlated well with the outside specialists' corresponding mean predictions (r = 0.97; p = 0.0001). We conclude that specialists are less consistent in predicting glycaemic change with exercise than with dietary alteration. Nevertheless it is possible to represent their predictions in a computerized simulator for diabetic patient education.
The Size of the Pancreas in Diabetes Mellitus
Authors: Alzaid A. , Aideyan O. , Nawaz S.
Published: July 2009

To determine whether there was an association between the size of the pancreas and the type of diabetes, ultrasonography of the pancreas was performed on 57 diabetic patients: 14 with Type 1 (insulin‐dependent) diabetes, 10 insulin‐treated and 33 tablet‐treated patients with Type 2 (non‐insulin‐dependent) diabetes, and 19 non‐diabetic subjects. The pancreas of patients with Type 1 diabetes was markedly smaller (p < 0.0001) than the pancreas in non‐diabetic subjects. The pancreas of patients with Type 2 diabetes was more moderate in size: larger (p < 0.001) than that of Type 1 diabetic patients but smaller (p < 0.5) than the pancreas of the control group. Pancreatic size of patients with Type 2 diabetes was also related to basal insulin secretion with insulin‐deficient patients (low or undetectable C‐peptide) having smaller (p < 0.05) pancreases than those with normal insulin secretion. There was no difference in the size of the pancreas in the different treatment groups of Type 2 diabetic patients. Pancreatic size did not correlate with age, body mass index or the duration of diabetes. We conclude that the pancreas is a smaller organ in patients with diabetes mellitus and that the decrement in size is maximal in insulin‐dependent/insulin‐deficient subjects. Ultrasonography, therefore, can potentially serve to discriminate between the different types of diabetes.
Increased Red Cell Sodium Lithium Countertransport Activity, Total Exchangeable Sodium, and Hormonal Control of Sodium Balance in Normoalbuminuric Type 1 Diabetes
Authors: Winocour P.H. , Catalano C. , Thomas T.H. , Wilkinson R. , Alberti K.G.M.M.
Published: July 2009

The relationship between erythrocyte sodium lithium countertransport activity (SLC), total exchangeable sodium (NaE), and hormonal control of renal function was examined in 40 normotensive, normoalbuminuric, non‐neuropathic Type 1 diabetic subjects, of whom 8 had elevated SLC (> 0.40 mmol Li h−1l−1 rbc). Eleven health controls with normal SLC, who were of comparable age, body mass, and blood pressure were also studied. By contrast with healthy controls, SLC in Type 1 diabetes was not associated with plasma renin activity (PRA), aldosterone, systolic blood pressure or lean body mass. SLC was also unrelated to atrial natriuretic peptide (ANP) (Type 1 diabetes only) and NaE. NaE was not correlated with any other variables. The relationships between PRA and aldosterone in healthy controls were retained in Type 1 diabetes (R2 0.37 supine, p = 0.00001, and 0.27 ambulant, p = 0.0005), as were respective direct and inverse relations between vasopressin and ANP and both PRA (rs 0.54 to 0.57, rs −0.43 to −0.53), and aldosterone (rs 0.78 to 0.80, rs −0.71 to −0.80). Fasting free serum insulin and vasopressin were both inversely related to ANP (rs −0.91 and −0.71, respectively). In the absence of autonomic dysfunction, hypertension or early nephropathy in Type 1 diabetes, increased SLC or exchangeable sodium were unrelated to each other or with hormonal control of sodium balance, but the homeostatic factors controlling hormonal interaction appear to be maintained. The interaction between insulin and hormonal control of sodium and water balance may be modified by circulating free insulin concentrations.
Insulin Therapy Increases Low Plasma Growth Hormone Binding Protein in Children with New‐onset Type 1 Diabetes
Authors: Arslanian S.A. , Menon R.K. , Gierl A.P. , Heil B.V. , Foley T.P.
Published: July 2009

This study was undertaken (1) to evaluate growth hormone binding protein (GHBP) levels in newly diagnosed patients with Type 1 diabetes before and after insulin therapy and (2) to determine the relationship of GHBP to glycaemic control, C‐peptide level and blood pH. GHBP, expressed as a percentage of (125I)GH bound, was determined in 33 patients with Type 1 diabetes (M/F = 19/14, 12.3 ± 0.4 years) before (day 0), after 5 days (day 5) and after 3 months (month 3) of insulin therapy. At day 0, GHBP was lower in Type 1 diabetes compared with 38 matched healthy control subjects (3.9 ± 0.4 vs 8.2 ± 0.4 %, p < 0.001). There was no significant improvement in GHBP at day 5 (4.4 ± 0.3 %). At month 3, GHBP increased to (6.0 ± 0.4 %, p < 0.001 vs day 0), but was still lower than controls, p < 0.001. At day 0 GHBP correlated with BMI (r = 0.50, p = 0.001), blood glucose (r = −0.43 p = 0.006) and pH (r = 0.48, p = 0.004), but not HbA1. GHBP at month 3 correlated with day 0 C‐peptide (r = 0.41, p = 0.02). Thus, (1) circulating GHBP is low in newly diagnosed patients with Type 1 diabetes, and increases after 3 months of insulin therapy but does not normalize and (2) the severity of biochemical derangement and residual β‐cell function at diagnosis may determine GHBP status and its recovery. We conclude that insulin is an important modulator of GH binding protein in newly diagnosed children with Type 1 diabetes.
The Clinical Diagnosis of Sensory Neuropathy in Elderly People
Authors: Thomson F.J. , Masson E.A. , Boulton A.J.M.
Published: July 2009

Minor abnormalities in sensory perception are common in elderly people but the significance of these findings is uncertain. In order to define the most relevant clinical tests for the diagnosis of significant neuropathy in the elderly diabetic patient, quantified perception of vibration, temperature, pain, and light touch was assessed in 200 (100 hospitalized, 100 community) consecutive non‐diabetic elderly subjects without apparent neurological disease, using an established scoring system. The changes in sensory perception were similar in the two groups and data were pooled for further analysis. Progressive loss of peripheral sensation was apparent with increasing age (neuropathy deficit score vs age: r = 0.4, p < 0.0001). Loss of vibration perception was particularly marked; deficit scores for vibration were significantly lower in the < 70 years age group than in all the older age groups (vibration score: < 70 years vs 80–84 years mean (95 % CI) 0.89 (0.54) vs 3.02 (0.6), p < 0.0001). In contrast, perception of light touch and pain was relatively preserved in old age. Assessment of vibration perception is of limited value in elderly people since the distinction between ‘normal ageing’ and significant neuropathy is unclear. Perception of light touch and pain are likely to be the most reliable clinical indicators of significant neuropathy in an elderly diabetic population.
Assessment of Diabetes Education in the Teaching Hospital, Addis Ababa, Ethiopia
Authors: Bahru Y. , Abdulkadir J.
Published: July 2009

With the aim of assessing continuing diabetes education and obtaining baseline information, we have evaluated the knowledge of 139 randomly selected diabetic patients from the Diabetes Clinic of Tikur Anbessa Teaching Hospital, Addis Ababa, Ethiopia. Seventy‐five Type 1 (insulin‐dependent) and 64 Type 2 (non‐insulin‐dependent) diabetic patients, with a mean age of 36 ± 14 (± SD) (range 15–78, median 36) years, and mean duration of known diabetes 6.3 ± 5.5 (range 1–30, median 5) years participated in the study. Knowledge was assessed by a questionnaire which examined three principal areas: general knowledge on diabetes mellitus, diet plus self care, and chronic complications. Twenty‐eight (20.1 %), did not attend any and 59 (42.5 %) attended the diabetes education programme more than once. The Adjusted Percentage Score (APSCORE) was 69 ± 1.4 (SEM). Type 1 diabetic patients had a significantly higher score (p < 0.001) for overall knowledge when compared to Type 2 patients. In both groups the knowledge on chronic complications was very poor when compared to the other areas (p < 0.001). No sex difference in knowledge was seen. Higher school and diabetes education attendance had a significant influence on the knowledge of diabetes. However, better knowledge about diabetes was not associated with better glycaemic control as measured by the fasting blood glucose concentration. The wide difference in knowledge, the low rate of attendance at diabetes education sessions, and the very low awareness about chronic complications is very worrying. To achieve the intended aim the diabetes education programme needs to be revised.
Increased Red Cell Aggregation in Diabetes Mellitus: Association with Cardiovascular Risk Factors
Authors: MacRury S. , Lennie S.E. , McColl P. , Balendra R. , MacCuish A.C. , Lowe G.D.O.
Published: July 2009

Red cell aggregation may be higher in diabetic patients and may predispose to cardiovascular disease. Red cell aggregation was measured by a simple photometric method in 122 diabetic patients and 100 matched control subjects, to determine its relationship to cardiovascular risk factors. Red cell aggregation was significantly increased in both Type 1 (4.3 ± 1.3 vs 3.4 ± 1.2, p < 0.002) and Type 2 diabetic patients (5.5 ± 1.5 vs 3.2 ± 1.3, p < 0.0001). In all diabetic patients aggregation correlated with triglycerides, VLDL, and inversely with HDL and in Type 2 diabetic patients also with body mass index, hypertension, and inversely with duration of diabetes. On multiple regression analysis, triglycerides and body mass index showed an independent association with red cell aggregation and in Type 2 diabetic patients smoking was also associated with increased red cell aggregation. It is concluded that increased red cell aggregation may be one mechanism by which some cardiovascular risk factors could promote cardiovascular disease in diabetes.