bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Exposure to Rubella Virus Generate Endocrine Autoimmunity?
Authors: Bodansky H.J. , Dean B.M. , Grant P.J. , McNally J. , Schweiger M.S. , Hambling M.H. , Bottazzo G.F. , Wales J.K.
Published: July 2009

Rubella virus is a possible environmental agent which may be involved in triggering autoimmunity to pancreatic islet cells, leading to Type 1 diabetes. Autoantibody responses were determined in 239 10‐year‐old girls who received live attenuated rubella vaccine, of whom 61 (26%) had no pre‐existing rubella immunity. Islet cell antibodies (ICA > 5 Juvenile Diabetes Foundation (JDF) units) were present in seven (2.9%) girls before vaccination, and they appeared in three more 6 weeks after vaccination (4.2%). However, the ICA levels were low in all cases and of the three girls who developed ICA > 5 JDF units 6 weeks post‐vaccination, none had detectable ICA 18 months later. IgG‐insulin autoantibodies were present in 17 (7.1%) girls before vaccination, and their prevalence decreased after vaccination (5.4%). Thyroid antibodies (thyroglobulin and microsomal) were present in 2% and 1%, respectively, of the girls before vaccination and none appeared afterwards. Thus, rubella vaccination did not elicit widespread endocrine autoantibody production and viral triggering of endocrine autoimmunity in susceptible subjects remains an open question.
Lens Opacity and Mortality in Diabetes
Authors: Cohen D.L. , Neil H.A.W. , Sparrow J. , Thorogood M. , Mann J.I.
Published: July 2009

A population‐based cohort of 294 diabetic patients were examined for the presence of lens opacities and followed up for a median of 6 years. Only two patients were lost to follow‐up but there were 73 deaths, 49 in the 108 patients with opacities and 24 in the 184 patients without (odds ratio 2.4, 95% Cl 1.5–3.9). Lens opacities were a powerful predictor of death and the effect was independent of other prognostic factors. The presence of cataract identifies a high risk sub‐group of elderly diabetic patients.
Insulin‐like Growth Factor Binding Protein‐1 Levels in Diabetic Adolescents and their Relationship to Metabolic Control
Authors: Holly J.M.P. , Dunger D.B. , Edge J.A. , Smith C.P. , Chard T. , Wass J.A.H.
Published: July 2009

Circulating levels of the low molecular weight insulin‐like growth factor binding protein‐1 (IGFBP‐1) are insulin dependent and vary markedly throughout the day. IGFBP‐1 levels are abnormally high in diabetes but the relationship between this and the metabolic status of the patient has not been defined. We have therefore measured fasting IGFBP‐1 levels at 0800 h in 32 diabetic adolescents. IGFBP‐1 was measured in 19 of these patients after a normal night and in 27 after a night of euglycaemia, maintained with a glucose clamp. In 13 patients both studies were performed and could be compared. Puberty‐matched control data were obtained from 69 normal children. In normal prepubertal children IGFBP‐1 levels were high; lower levels were found with advancing pubertal development. This fall in IGFBP‐1 correlated with pubertal stage (r = 0.68, p < 0.001) and with fasting insulin levels (r = 0.60, p < 0.001) which rose with pubertal advancement. In the diabetic children IGFBP‐1 levels also correlated inversely with the 0800 h free insulin level but there was no clear relationship with pubertal development. However, when measured after overnight euglycaemia IGFBP‐1 levels correlated inversely with pubertal development (r = 0.67, p < 0.001) as in the normal children. In the patients studied on two comparable occasions the IGFBP‐1 level measured after a normal night relative to that measured under standardized euglycaemic conditions was found to correlate closely with the glycosylated haemoglobin level (r = 0.71, p < 0.005).
Information Technology for Diabetes Care in Europe: the EURODIABETA Initiative
Authors:   ËRODIABETA
Published: July 2009

The EURODIABETA project is a European Community supported project to examine the feasibility of applying information technology to improve health care in the field of chronic disease using diabetes as an example. In April 1990 physicians and information scientists from all over Europe came together and examined the potential of the project in a series of workshops. As a result physicians were convinced of the applicability of a modelling process to describe health care delivery and recommended that the project be continued. They further reviewed a data set conceived to allow description of the status of a person with diabetes and concluded that it was possible to review and explain diabetes care with this tool.
Comparative Effects of Two Different Multiple Injection Regimens on Blood Glucose Control and Patient Acceptance in Type 1 Diabetes
Authors: Wolffenbuttel B.H.R. , van Ouwerkerk B.M. , Veldhuyzen B.F.E. , Geelhoed‐Duijvestijn P.H.L.M. , Jakobsen G. , van Doorn L.G.
Published: July 2009

In a randomized cross‐over study we compared blood glucose control and patient acceptance of a 12‐week basal‐prandial regimen with short‐acting insulin before meals and isophane (NPH) insulin at bedtime (4 injections) with a scheme with a second injection of isophane (NPH) insulin before breakfast (5 injections). Forty‐three Type 1 diabetic patients (age 37 ± 11 (± SD) years, duration of diabetes 15 (range 2–48) years, 26 males and 17 females) completed the study. Mean daily blood glucose was 8.6 ± 2.4 mmol I−1 at baseline, and 8.1 ± 2.2 mmol I−1 after the four‐injection period and 7.9 ± 2.0 mmol I−1 with five‐injections (NS). HbA1c after 12 weeks was not different with the two treatments (6.6 ± 1.1 vs 6.5 ± 0.9%), neither was fasting blood glucose (9.6 ± 4.2 mmol I1c with 4 injections, and 9.0 ± 4.4 mmol I−1 with 5 injections). Daily insulin dose did not differ between regimens (55 vs 56 U day −1). No differences in number or severity of hypoglycaemic events were observed. After the study, 13 patients preferred to continue the 5‐injection regimen, and 21 patients preferred 4 injections. Treatment satisfaction with either regimen was equally high. It is concluded that dividing the intermediate‐acting insulin into a morning and an evening dose did not lead to an improvement in blood glucose control in these moderately‐controlled Type 1 diabetic patients.
Lack of Effects of Angiotensinconverting Enzyme (ACE)‐inhibitors on Glucose Metabolism in Type 1 Diabetes
Authors: Seefeldt T. , Ørskov L. , Mengel A. , Rasmussen O. , Pedersen M.M. , Møller N. , Christiansen J.S. , Schmitz O.
Published: July 2009

To evaluate the impact of ACE‐inhibitors on insulin‐mediated glucose uptake, glucoseinduced glucose uptake, and hepatic glucose production, a sequential glucose clamp was performed in eight normotensive Type 1 diabetic patients after 3 weeks of enalapril therapy 20 mg day−1 and during control conditions. The experiments were carried out in random order. Mean arterial blood pressure was significantly reduced during ACE‐inhibition (95 ± 3 (±SE) vs 84 ± 3 mmHg; p < 0.02), while blood glucose control as assessed by HbA1c was unaltered (7.9 ± 0.5 vs 7.6 ± 0.5%). The night prior to the study normoglycaemia was maintained by a Biostator. A two‐step hyperinsulinaemic euglycaemic clamp (insulin infusion rate 0.3 and 0.8 mU kg−1 min−1) was followed by a hyperinsulinaemic and hyperglycaemic clamp (insulin infusion rate 0.8 mU kg−1 min−1, plasma glucose 11 mmoll−1). Insulin concentrations were comparable with and without enalapril treatment. During the hyperinsulinaemic clamps isotopically determined glucose disposal was unchanged (low dose 2.5 ± 0.3, high dose 4.3 ± 0.7 vs 2.6 ± 0.3 and 4.3 ± 0.7 mg kg−1 min−1 enalapril vs control). Glucose‐induced glucose disposal (9.2 ± 1.2 vs 9.1 ± 1.2 mg kg−1 min1) was also similar, as were non‐protein respiratory exchange ratios (indirect calorimetry). Glucose production was not changed by enalapril. In conclusion, treatment with enalapril has no significant effect on glucose metabolism in Type 1 diabetes.
Unawareness of Hypoglycaemia in Insulin‐treated Diabetic Patients: Prevalence and Relationship to Autonomic Neuropathy
Authors: Hepburn D.A. , Patrick A.W. , Eadington D.W. , Ewing D.J , Frier B.M.
Published: July 2009

Three‐hundred and two insulin‐treated diabetic patients were questioned about hypoglycaemia using a structured questionnaire interview. Two‐hundred and twenty‐six patients (75%) had normal symptomatic awareness, 48 (16%) had partial awareness, 21 (7%) had absent awareness of hypoglycaemia, and 7 (2%) denied ever experiencing hypoglycaemia. Patients with complete loss of awareness of hypoglycaemia had diabetes of longer duration; none had a HbA1c concentration within the non‐diabetic range. Loss of awareness of hypoglycaemia was associated with an increased incidence of severe hypoglycaemia, 19 (91%) of the patients with absent awareness, and 33 (69%) with partial awareness of hypoglycaemia experiencing severe hypoglycaemia over 1 year compared with only 41 (18%) of patients with normal awareness of hypoglycaemia (p < 0.001). Cardiovascular autonomic function tests were performed in 226 (75% of the whole group). Of the patients who had diabetes for more than 15 years, 54% (n = 39) with normal awareness of hypoglycaemia, compared with 59% (n = 10) with absent awareness of hypoglycaemia, had evidence of cardiovascular autonomic impairment (NS). Seven (41%) of the 17 patients with absent awareness of hypoglycaemia and diabetes of > 15 years duration had no evidence of autonomic dysfunction. Loss of hypoglycaemia awareness is a common problem in patients with insulin‐treated diabetes of long duration, is associated with an increased incidence of severe hypoglycaemia, but is not invariably associated with abnormal cardiovascular autonomic function tests.
The Metabolic Associations of Intravenous Glucose Tolerance in the 10 Years from Diagnosis of Type 2 Diabetes
Authors: Coppack S.W. , Yajnik C.S. , Doll H.A. , Thursfield V. , Hockaday T.D.R.
Published: July 2009

Intravenous glucose tolerance was measured at diagnosis and during the subsequent 10 years in 103 Type 2 diabetic patients not treated with insulin. KG (the rate constant for clearance of intravenous glucose) was inversely related to fasting plasma glucose at all review times (at diagnosis being Rs = −0.77, p < 0.001), and at times to the circulating concentrations of ketone bodies (at diagnosis being Rs = −0.52, p < 0.001) and glycerol (Rs = −0.29, p < 0.01). In the first year of treatment, most metabolic abnormalities improved. One to 10 years after diagnosis, fasting glucose concentration and intravenous glucose tolerance deteriorated (median glucose from 6.4 to 7.4 mmol I−1, p < 0.001; median KG from 0.81 to 0.69 % min−1, p < 0.01). Likewise, the ‘homeostatic model assessment’ of insulin insensitivity deteriorated (median from 2.3 to 3.7 arbitrary units, p < 0.001) over the same period but first‐phase insulin secretion remained steady or improved. This suggests that increases in insulin insensitivity have a predominant effect on slowly deteriorating glucose tolerance from 1 to 10 years after diagnosis in Type 2 diabetes.
A Preliminary Multicentre Study of the Treatment of Recently Diagnosed Type 1 Diabetes by Combination Nicotinamide‐Cyclosporin Therapy
Authors: Vialettes B. , Picq R. , du Rostu M. , Charbonnel B. , Rodier M. , Mirouze J. , Vexiau P. , Passa Ph. , Pehuet M. , Elgrably F. , Vague Ph.
Published: July 2009

The aim of the present study, a pilot trial, was to find out if nicotinamide (50 mg kg−1 day−1) in combination with cyclosporin A favours remission in recently diagnosed Type 1 diabetic patients, and if it postpones relapse even when cyclosporin A is administered in decreasing doses (trough blood level 300–500 (μg l−1 until month 4, and 100–300 μg l−1 until month 9) and then discontinued. The criteria for inclusion in the study and the follow‐up protocol were the same as those used in the Cyclosporin Diabetes France (CDF) programme in which all five of the centres involved in this study participated. The data of the present preliminary open study were therefore compared retrospectively with those of the placebo (CDF‐placebo) and cyclosporin (CDF‐active) group of the CDF programme. Clinical remission (fasting plasma glucose <7.8 mmol l−1, postprandial plasma glucose < 11.1 mmol l−1, HbA1c < 7.5 % with neither insulin nor oral hypoglycaemic agents) was achieved within 6 months in 12 out of 35 patients (34 %) vs 16 out of 63 (25 %) in CDF‐active and 11 out of 59 (19 %) in CDF‐placebo. Remission was achieved by month 9 in 6 out of 35 patients (17 %) vs 13 out of 54 (24 %) in CDF‐active and 3 out of 52 (6 %) in CDF‐placebo. By 12 months remission persisted in 3 out of 35 patients (9 %) vs 11 out of 63 (17 %) in CDF‐active and 0 out of 52 (0 %) in CDF‐placebo. Only CDF‐active at months 9 and 12 was significantly different from CDF‐placebo (p < 0.05). The daily insulin doses of the nicotinamide‐cyclosporin group were not different from those administered to CDF‐placebo patients at month 12. Post‐stimulation C‐peptide values were comparable to those measured in CDF‐active up to month 9 but dropped to a level comparable to those measured in CDF‐placebo when cyclosporin A was discontinued. Combining nicotinamide with cyclosporin A does not significantly improve the remission rate and does not prolong remission after discontinuation of cyclosporin A.
Morphology of Palpably Abnormal Injection Sites and Effects on Absorption of Isophane(NPH) Insulin
Authors: Thow J.C. , Johnson A.B. , Marsden S. , Taylor R. , Home P.D.
Published: July 2009

The absorption of isophane(NPH) insulin (Human Insulatard) from palpably abnormal thigh insulin injection sites was determined in 10 C‐peptide negative diabetic patients. Absorption was compared with a control day study when the insulin was injected into normal thigh. Standard meals were given 30 and 240 min after the injection. Within 2 weeks the tissue morphology and adipose tissue depths at both injection sites were assessed by ultrasound scanning. Absorption of isophane(NPH) insulin was markedly defective from the abnormal compared with the normal injection sites (area under the free insulin curve to 10 h 115 ± 15 vs 188 ± 21 mU I−1 h; p < 0.01). The area under the blood glucose curve from 270 min to the end of the study at 600 min was significantly greater after injection into the palpably abnormal injection site compared with normal thigh (80.4 ± 5.2 vs 61.2 ± 7.0 mmol I−1 h; p < 0.05) representing a 22 % improvement in blood glucose control on the normal injection site afternoon. The depth of abnormal injection site tissue was significantly greater than the depth of adipose tissue at the control site (17 ± 6 vs 5 ± 4 mm; p < 0.001) and considerable disruption of the normal anatomy observed. These results demonstrate defective absorption of isophane(NPH) insulin from palpably abnormal injection sites and describe the morphology of the abnormal tissue.
Insulin Supplement in Type 2 Diabetic Patients with Secondary Failure to Oral Agents Ameliorates Hepatic and Peripheral Insulin Sensitivity but not Insulin Secretion
Authors: Pisu E. , de Benedictis D. , Baggiore C. , Diana A. , Marengo C. , Bozzo C. , Renzetti A. , Pagano G.
Published: July 2009

In order to investigate the mechanism of amelioration of metabolic abnormalities with supplementary doses of insulin, islet B‐cell function and insulin sensitivity were measured in 10 patients with Type 2 diabetes in secondary failure to oral agents. A small dose of ultralente insulin (0.26 ± 0.07 U kg‐ideal‐body‐weight−1) was added in the morning before breakfast. After 3 months insulin therapy and progressive improvement of metabolic control (HbA1 from 10.5 ± 0.4 to 9.0 ± 0.3 % at the end of insulin treatment, p < 0.001), basal C‐peptide and incremental area during an oral glucose tolerance test were unchanged. In vivo peripheral insulin sensitivity (euglycaemic clamp with insulin infusion of 40, 160, and 600 mU m−2 min−1, respectively) was significantly improved (glucose requirement: to 4.7 ± 1.0 from 3.0 ± 0.6 mg kg−1 min−1, p< 0.05 at first insulin level; to 10.8 ± 0.5 from 9.3 ± 0.7 mg kg−1 min−1, p<0.01 at second level; to 13.3 ± 0.6 from 11.8 ± 0.8 mg kg−1 min−1, p< 0.025 at third level). Basal hepatic glucose production was also significantly reduced (from 4.3 ± 0.4 to 3.3 ± 0.3 mg kg−1 min−1, p< 0.05), and residual glucose production further suppressed after insulin supplement (from 1.1 ± 0.4 to 0.3 ± 0.2 mg kg−1 min−1 after 120 min at 100 mU I−1 plasma insulin, p< 0.05). Specific insulin binding to mononuclear leucocytes was unchanged (from 3.1 ± 0.3 to 3.5 ± 0.3 %, NS).
A Comparative Study of Microvascular Complications in Patients with Secondary and Type 1 Diabetes
Authors: Larsen S. , Hilsted J. , Philipsen E.K. , Lund‐Andersen H. , Parving H‐H. , Worning H.
Published: July 2009

The prevalences of retinopathy, albuminuria, and neuropathy were assessed in 25 patients with insulin‐requiring diabetes secondary to chronic pancreatitis and in 25 patients with Type 1 (insulin‐dependent) diabetes, matched for age at diabetes onset (secondary, 39 ± 11 (± SD) years vs Type 1, 38 ± 11 years) and duration of diabetes (10 ± 6 vs 10 ± 7 years). The prevalence of retinopathy was significantly higher in Type 1 diabetic patients (52 %) than those with secondary diabetes (20 %) (p < 0.02). Median urinary excretion of albumin was 9 (range 1–206) mg 24‐h−1 in patients with Type 1 diabetes and 7 (1–90) mg 24‐h−1 in patients with secondary diabetes (NS). One secondary diabetic patient and five Type 1 diabetic patients had microalbuminuria (NS). Vibration perception threshold (measured at the big toe) was identical in the two groups of patients, and no patient had a threshold indicating somatic neuropathy (biothesiometry > 20 V). Retinopathy is more frequent in patients with Type 1 diabetes than in patients with insulin‐requiring diabetes secondary to chronic pancreatitis. Retinopathy is so frequent in the latter group, however, that regular ophthalmoscopic examination is still required.
Comparison of Glycosylated Fibrinogen, Albumin, and Haemoglobin as Indices of Blood Glucose Control in Diabetic Patients
Authors: Ardawi M.S.M. , Nasrat H.N. , Mira S.A. , Fatani H.H.
Published: July 2009

The value of glycosylated fibrinogen as an index of short‐term diabetic control was compared with indices of long‐term (glycosylated haemoglobin) and intermediate‐term (glycosylated albumin) diabetic control, respectively. In this study, percentages of these glycosylated proteins and fasting plasma glucose concentration were determined in 95 healthy non‐diabetic subjects and 48 diabetic patients (22 well‐controlled and 26 poorly‐controlled) after an overnight fast. The differences in the percentages of glycosylated fibrinogen, haemoglobin, and albumin between non‐diabetic subjects (4.7, 6.4, and 2.0), well‐controlled diabetic patients (6.9, 9.5 and 2.9), and poorly‐controlled diabetic patients (11.3, 15.8, and 5.1) were statistically significant (p<0.05). The percent glycosylated fibrinogen exhibited significant association with severity of hyperglycaemia when diabetic patients were divided by 2, 4, and 6 standard deviations above the mean of fasting plasma glucose of non‐diabetic subjects. There were significant correlations between glycosylated fibrinogen and fasting plasma glucose (r = 0.83, p < 0.001), glycosylated haemoglobin (r=0.94, p< 0.001) and glycosylated albumin (r = 0.92, p< 0.001) for all subjects studied. In ten newly diagnosed diabetic patients after 6 days of treatment, only the decrease in glycosylated fibrinogen (33.4 %) was significant (p < 0.05), but not that of glycosylated haemoglobin (4.8 %) or albumin (8.0 %). It is suggested that glycosylated fibrinogen provides the clinician with earlier objective evidence of the metabolic response to therapeutic intervention, and might be regarded as a short‐term (2–3 days) index of blood glucose control.
Knowledge, Attitudes, Technical Competence, and Blood Glucose Control of Type 1 Diabetic Patients During and After an Education Programme
Authors: Lennon G.M. , Taylor K.G. , Debney L. , Bailey C.J.
Published: July 2009

Thirty‐one Type 1 diabetic patients entered a 12‐month education programme in which attitudes to diabetes, knowledge of diabetes, and technical competence were assessed using questionnaires and practical tests. A closely matched group of 25 control patients continued to receive routine clinic care. Patients completing the education programme showed improved blood glucose control (HbA1 decreased from 11.8 ± 0.4% to 10.5 ± 0.3 %, mean ± SE, p <0.01), whereas blood glucose control was not altered in the control group (HbA1 11.8 ± 0.5 % before and 11.6 ± 0.4 % after 12 months). Patients completing the education programme also showed greater knowledge (p<0.001), more favourable attitudes (p <0.03), and increased competence in technical skills (p <0.02) compared with the control group. Six months after completing the programme blood glucose control deteriorated (HbA1 11.0 ± 0.4 %, p <0.05), although knowledge, attitudes, and technical competence were unchanged. This might reflect the withdrawal of extrinsic motivation and attention provided during the programme. Thus consideration should be given to development of the patient's intrinsic motivation to prolong the benefits of diabetes education programmes.
Effect of Insulin‐induced Hypoglycaemia on Absorption of Unmodified Insulin after Subcutaneous or Intramuscular Injection
Authors: Grønlund B. , Frandsen H. , Lauritzen M. , Nielsen S. Levin , Madsbad S.
Published: July 2009

The effect of insulin‐induced hypoglycaemia on the absorption of iodine‐125 labelled unmodified insulin (10 U) from thigh after subcutaneous or intramuscular injection was studied in eight immobilized, supine, normal subjects. Ultrasonic determination of the subcutaneous thickness was used to accurately localize the site for insulin injection. Insulin absorption was studied twice during hypoglycaemia or normoglycaemia in random order. Insulin absorption was similar after subcutaneous and intramuscular injections (residual activity at 5 h: SC 59.3 ± 5.0 (± SE)%; IM 55.2 ± 3.7%). Hypoglycaemia did not change the disappearance rate of iodine‐125 insulin after either subcutaneous (55.0 ± 4.4%) or intramuscular injection (52.6 ± 5.7%), despite a plasma glucose nadir of 1.7 ± 0.2 mmol I−1. In a controlled study under standardized conditions hypoglycaemia has no effect on insulin absorption rate.
The Swedish Childhood Diabetes Study: a Seven‐fold Decrease in Short‐term Mortality?
Authors: Sartor G. , Nyström L. , Dahlquist G.
Published: July 2009

Since 1 July 1977 all Swedish children aged 0–14 years with newly diagnosed Type 1 diabetes have been recorded on a central register. Out of 3228 patients registered up to 31 December 1985, 10 children (seven boys) had died during this time period. The overall mortality was 0.75 per 1000 patient‐years. When compared with the general population the standardized mortality ratio (SMR) for both sexes was 2.09 (95% confidence limits 1.14–3.83). When analysed separately for sex, the higher mortality remained significant for males only (SMR = 2.61, 1.28–5.32). Five deaths were most probably due to diabetes and the remaining five were due to accidents, other diseases and, in one case, not identifiable with certainty. In comparison with previous studies there was a very low mortality in young‐onset diabetic patients. However, short‐term mortality is still significantly raised even in a country with a good economic and educational patient status and easy access to free hospital care
Unexplained Deaths of Type 1 Diabetic Patients
Authors: Tattersall R.B. , Gill G.V.
Published: July 2009

The suggestion of an increase in the number of sudden deaths of young people with Type 1 diabetes in the UK has been investigated. It was suggested that such deaths were due to hypoglycaemia and related to the increasing use of human insulin. In total we were notified of 50 deaths of people with Type 1 diabetes under age 50 years in the UK in 1989 which our informants (relatives, physicians, and pathologists) considered sudden and unexpected. An autopsy had been done in all cases and we supplemented this with detailed clinical information from relatives and case records. Of the 50 cases we excluded five with a definite cause of death, 11 suicides or self‐poisonings, six cases of ketoacidosis, and four in which there was insufficient information about the circumstances of death to drawn any conclusions. Of the other 24 cases, two patients had been found with irreversible hypoglycaemic brain damage and died after a period of artificial ventilation. The most puzzling group were 22, aged 12–43 years, most of whom had gone to bed in apparently good health and been found dead in the morning. Nineteen of the 22 were sleeping alone at the time of death and 20 were found lying in an undisturbed bed. Most had uncomplicated diabetes and in none were anatomical lesions found at autopsy. There are major difficulties in diagnosing hypoglycaemia post‐mortem, but the timing of death and other circumstantial evidence suggests that hypoglycaemia or a hypoglycaemia‐associated event was responsible. All patients were taking human insulin at the time of death but most had been changed from animal insulin between 6 months and 2 years earlier and there was nothing to implicate the species of insulin as a factor in these deaths
Deterioration in Blood Glucose Control in Females with Diabetes Changed to a Basal‐bolus Regimen Using a Pen‐injector
Authors: Hardy K.J. , Jones K.E. , Gill G.V.
Published: July 2009

Although the basal‐bolus regimen of insulin delivery is more physiological than conventional twice daily insulin it does not usually improve blood glucose control. Having recently withdrawn 3 patients from pen‐injector therapy for deteriorated blood glucose control we examined the records of all our diabetic patients on a pen‐injector for at least 1 year. Of the 51 patients identified, 3 had died, 2 moved away, and 4 patients (3 females) had pen‐injector therapy withdrawn for poor control; 3 patients had inadequate records. The remaining 21 males and 18 females were well matched for age, duration of diabetes, and duration of pen‐injector treatment. Blood glucose control deteriorated significantly during pen‐injector therapy in female patients (9.6 ± 1.2 to 10.7 ± 1.4%, p = 0.02), but not in the males (9.3 ± 1.3 vs 9.4 ± 1.4%, NS). Weight and insulin dose did not change significantly in any patient. Blood glucose control may deteriorate in young women with diabetes changed to insulin therapy with a pen‐injector
Does Knowledge of Islet Cell Antibody Status Help in Managing Diabetes Presenting in Middle and Old Age?
Authors: Gregory R. , Tattersall R.B.
Published: July 2009

It has been suggested that screening all patients with diabetes diagnosed in later life for islet cell antibodies (ICA) would help predict insulin dependence. We have surveyed the case notes of 55 patients (22 male; ages 37–88 years) who were found to be ICA positive over a 9‐year screening period to assess what contribution knowledge of ICA status made to their management. Forty‐two patients had been put on insulin (half within 6 months of diagnosis and the rest after up to 6 years). Of the 13 patients not on insulin, six were on diet alone and seven on oral hypoglycaemic agents after a median follow‐up of 3 years. In 37 of the 42 patients, insulin treatment was started for clinical rather than immunological reasons (diabetic ketoacidosis, ketonuria, weight loss and/or severe symptoms). Five patients were started on insulin because of ICA status when there was no compelling reason on clinical grounds. Knowledge that seven non‐insulin‐treated patients were ICA positive made doctors reluctant to discharge them from clinic. The data suggest that routine ICA estimation in this age group is unnecessary, as the decision to treat with insulin is best made on clinical grounds, and ICA estimation can lead to unwarranted insulin treatment, or anxiety in patients and doctors who are aware of a positive result
Diabetes Mellitus in the Sultanate of Oman
Authors: Asfour M.G. , Samantray S.K. , Dua A. , King H.
Published: July 2009

In February 1990 a World Health Organization consultancy was undertaken to assess the current impact of diabetes mellitus in Oman. Routine national health statistics suggested that diabetes was the principal diagnosis in approximately 1% of all hospital discharges in 1988. The number of ‘new cases’ of diabetes treated at hospitals during the same year was 4.8 per 1000 Omani population, representing almost 6000 diabetic patients. In 1989, at the Royal Hospital, Muscat, diabetes was recorded as the principal diagnosis for 2.6% of all discharges, and 6% of those in subjects aged 45 years and over. It is known that the frequency of diabetes is generally underestimated by routine health statistics. Limited ad hoc investigation during the consultancy suggested that approximately 9% of all adult hospital admissions and 12% of adult hospital bed occupancy were associated with diabetes. Thus, diabetes should be considered a priority in a national health strategy for Oman. It is recommended that emphasis be placed upon epidemiological research, education, and the provision of appropriate technology
Neutrophil Aldose Reductase Activity as a Potential Marker for Neuropathy and Cataract in Diabetes
Authors: Dent M. T. , Veves A. , Tebbs S. E. , Gonzalez A. M. , Malik R. A. , Boulton A. J. M. , Ward J. D. , Wilson R. M.
Published: July 2009

Aldose reductase activity can be measured in the neutrophil and it has been proposed that this may be a marker for risk of complications in diabetes. We have studied aldose reductase activity in neutrophil, nerve, and lens in diabetic patients undergoing sural nerve biopsy or cataract extraction. A correlation was demonstrated between lens and neutrophil aldose reductase activity (r = 0.53, p = 0.01) but no correlations were demonstrated between nerve aldose reductase activities and nerve morphometry, nerve function or neutrophil aldose reductase activity. No significant difference was found between neutrophil aldose reductase activities in groups of patients with severe neuropathy, or cataract, or no complications (24 (interquartile range 16–32) vs 24 (16–40) vs 24 (16–40) nmol NADPH min−1 108‐cells −1). In a group of 56 Type 1 diabetic patients screened within 6 years of diagnosis, multiple regression analysis failed to show any relationship between neutrophil aldose reductase activity and abnormalities of neurophysiological function. These results suggest that neutrophil aldose reductase activity cannot be used as a marker for the development of cataract or neuropathy in diabetes.
Predominantly Vegetarian Diet in Patients with Incipient and Early Clinical Diabetic Nephropathy: Effects on Albumin Excretion Rate and Nutritional Status
Authors: Jibani M. M. , Bloodworth L. L. , Foden E. , Griffiths K. D. , Galpin O. P.
Published: July 2009

Several studies have suggested that dietary protein quality may be an important determinant in the natural history of renal disease. We have therefore studied the effects of a predominantly vegetarian diet in eight patients with Type 1 diabetes mellitus and an albumin excretion rate (AER) in excess of 30 μg min−1. The AER was measured after an 8‐week run‐in period on the patient's usual diet, and again after 8 weeks of a predominantly vegetarian diet in which the proportion of vegetable protein was supplemented in order to minimize the reduction in total dietary protein intake. The median fractional albumin clearance fell during the study from an initial value of 188 times 10−4 (range 58–810 times 10−4) at the end of the run‐in period to 87 times 10−4 (23–829 times 10−4) at the end of the period on low animal protein diet (difference 79 times 10−4 (95% Cl 9–149 times 10−4), p < 0.05). The AER then returned to values similar to those obtained at the beginning of the study after a further 8 weeks in those patients returning to their usual diet. No significant changes in blood glucose control or in arterial pressure were observed. A predominantly vegetarian diet may therefore have important beneficial effects on diabetic nephropathy without the need for a heavily restricted total protein intake.
Impaired Anal Sensation and Early Diabetic Faecal Incontinence
Authors: Aitchison M. , Fisher B. M. , Carter K. , McKee R. , MacCuish A. C. , Finlay I. G.
Published: July 2009

Faecal incontinence develops in up to 20% of diabetic patients. To try to determine the relative contributions of sensory and motor neuropathy in this troublesome complication, anorectal function was examined in 10 male diabetic patients with early faecal incontinence (mucus leakage or faecal staining without the need to wear a pad), 10 asymptomatic male diabetic patients, and 10 normal control subjects. Motor function was tested using anal manometry to determine the resting and maximum squeeze pressure, and the functional anal canal length. No significant differences were found between the groups. Sensory function was tested by measuring the mucosal sensitivity to electrical stimulation, and the response to inflation of a balloon in the rectum. In the mid‐anal canal position the symptomatic patients had a significantly higher sensory threshold at 6.6 ± 2.8 mA compared with 3.0 ± 1.2 mA in the normal control subjects (p < 0.002), and in the high anal zone symptomatic patients had a significantly elevated sensory threshold at 9.1 ± 2.0 mA compared with 4.6 ± 1.6 mA in asymptomatic patients and 3.6 ± 1.3 mA in the normal control subjects (both p < 0.001). There were no significant differences in the first sensation of fullness, maximum tolerated volume or percentage fall from resting pressure between the groups on inflation of the balloon. Elevation of the sensory threshold in the upper anal canal is an early abnormality in the development of diabetic faecal incontinence.
The Management of Impotence in Diabetic Men by Vacuum Tumescence Therapy
Authors: Price D. E. , Cooksey G. , Jehu D. , Bentley S. , Hearnshaw J. R. , Osborn D. E.
Published: July 2009

The treatment of impotence in diabetic men with vacuum tumescence therapy was studied in a specialist clinic. Of 54 diabetic men referred with impotence, seven declined treatment, three chose self‐injection with papaverine, and 44 chose vacuum therapy. Patients underwent autonomic function testing (heart rate response to respiration), measurement of penile blood flow (duplex Doppler scanning), and estimation of serum prolactin and testosterone levels. After 2 months, 33 men (75%) were able to have satisfactory intercourse using vacuum therapy. Three others could produce a satisfactory erection with vacuum therapy but their partners found it unacceptable. Eight men (18%) were unable to have satisfactory intercourse; six of these were later treated by self‐injection. The median frequency of use of vacuum therapy was 5.5 (1–26) times a month. Outcome was independent of penile blood flow, autonomic function or endocrine status. Impotent diabetic men should be given counselling and offered a choice of the available treatments. Vacuum tumescence therapy is an effective and simple treatment which requires little investigation.
Regression of Left Ventricular Hypertrophy with 1 Year of Antihypertensive Treatment in Type 1 Diabetic Patients with Early Nephropathy
Authors: Sampson M. J. , Chambers J. B. , Sprigings D. C. , Drury P. L.
Published: July 2009

M‐mode echocardiograms were recorded in 22 Type 1 diabetic patients with microalbuminuria (n = 10) or early persistent proteinuria (n = 12). Eight (36%) had both an increased left ventricular mass (males > 131 g m−2; females > 100 g m−2) and a systolic blood pressure above the 75th centile of the normal blood pressure distribution. These eight patients were treated with antihypertensive drugs, predominantly enalapril, for 1 year. Echocardiograms were repeated after 3 and 12 months. Systolic blood pressure at recruitment was 155 ± 14 (± SD) mmHg, and was significantly lower after 3 months (146 ± 12 mmHg; p < 0.05) and 12 months (139 ± 8 mmHg; p < 0.005). Diastolic blood pressure did not change significantly. Both intraventricular septal width and left ventricular posterior wall thickness fell progressively and were significantly lower after 12 months treatment (15.0 ± 2.7 vs 13.0 ± 2.6 mm, and 10.3 ± 1.9 vs 8.8 ± 1.3 mm; both p < 0.05). Left ventricular mass index was 148 ± 29 g m−2 at recruitment, but lower after 3 months (131 ± 25 g m−2; p < 0.05) and 12 months (132 ± 26 g m−2; p < 0.005) antihypertensive therapy.
Influence of Sample Type on the Interpretation of the Oral Glucose Tolerance Test for Gestational Diabetes Mellitus
Authors: Neely R. D. G. , Kiwanuka J. B. , Hadden D. R.
Published: July 2009

The World Health Organization (1985) criteria allow evaluation of the oral glucose tolerance test using venous or capillary whole blood or plasma glucose measurements. However, the empirical factors used for interconversion may not reflect observed differences, especially during pregnancy, causing inconsistent classification. To investigate how choice of sample would influence the interpretation of results, venous and capillary blood was taken during oral glucose tolerance tests in 36 pregnant women at risk of gestational diabetes and in 21 non‐pregnant control subjects. Glucose was measured on whole blood and plasma by a glucose oxidase method. No cases of gestational diabetes were identified. Eight subjects had gestational Impaired Glucose Tolerance using either venous plasma or venous whole blood results, but only five were similarly classified with capillary whole blood and only four using capillary plasma. Plasma‐whole blood differences (venous 0.6 ± 0.2 (±SD) mmol I−1, capillary 0.7 ± 0.3 mmol I−1) and capillary‐venous differences (plasma 0.5 ± 0.4, whole blood 0.4 ± 0.5 mmol I−1) at 2 h were lower (all p<0.05) than in the WHO criteria (1.1 mmol I−1). When compared with venous plasma, capillary measurements may give a lower incidence and venous whole blood measurements a higher incidence of Impaired Glucose Tolerance in pregnancy.
Diastolic Ventricular Function in Type 1 Diabetic Patients: A Study Using Doppler Echocardiography
Authors: Grossmann G. , Schmidt A. , Hauner H. , Göller V. , Stauch M. , Pfeiffer E.F. , Hombach V.
Published: July 2009

The transmitral flow velocity pattern of 28 Type 1 diabetic patients and 39 age‐matched healthy control subjects was studied for determination of left ventricular diastolic function. No patient had systemic hypertension, congestive heart failure, or ischaemic heart disease by clinical or electrocardiographic criteria. Echocardiographic measures of systolic ventricular function were within normal range in all subjects. The ratio of early to late transmitral peak flow velocity (ve/va) was significantly decreased in the diabetic patients (1.3 ± 0.1 (± SE) vs 1.6 ± 0.1, p < 0.05), while other Doppler derived variables did not show any significant difference. No correlation of ve/va with duration of diabetes was found (r = −0.27), but it correlated with age in both groups (both r = −0.40, p < 0.05). Furthermore, a significant correlation was found between ve/va and heart rate (r = −0.55 for diabetic patients, p < 0.01; r = −0.58 for control subjects, p < 0.01). After matching for heart rate (24 diabetic patients and 24 control subjects) no significant decrease of ve/va was observed in the diabetic group.
Risk Factors for Non‐ischaemic Foot Ulceration in Diabetic Nephropathy
Authors: Fernando D. J. S. , Hutchison A. , Veves A. , Gokal R. , Boulton A. J. M.
Published: July 2009

It is recognized that diabetic patients with nephropathy frequently have macrovascular disease leaving them at risk of ischaemic foot lesions. In order to assess non‐vascular risk factors for foot ulceration 64 patients were stratified into four groups: microalbuminuria, albuminuria with creatinine clearance > 40 ml min−1, chronic renal failure (clearance < 40 ml min−1), and a non‐nephropathic diabetic control group. Vibration perception threshold was measured by biothesiometry, peroneal nerve conduction velocity by conventional methods, and dynamic foot pressure by pedobarography. Vibration perception threshold was elevated in all three groups when compared with age‐matched normal and diabetic control groups. Mean vibration perception threshold was 20.8 ± 8.6 (±SD) in the microalbuminuria group (p < 0.001 compared with age‐matched normal control group), 28.1 ± 5.6 (p < 0.001) in the albuminuria group, 38.9 ± 9.4 (p < 0.001) in the renal failure group, 14.8 ± 5.2 in the diabetic control group and 12.3 ± 2.9 in the normal control group. Peroneal motor conduction velocity was reduced in all three groups when compared with normal control subjects, microalbuminuria 38.6 ± 4.2 m s−1 (p < 0.001), albuminuria 38.0 ± 6.1 m s−1 (p < 0.01), renal failure 35.5 ± 1.2 m s−1 (p < 0.001), diabetic control 40.6 ± 1.8 m s−1, and normal 43.1 ± 2.3 m s−1. Mean peak plantar foot pressure was elevated in all three groups when compared with age‐matched normal anddiabetic control groups (p < 0.01), microalbu‐minuria 12.2 ± 3.1 kg cm−2, albuminuria 14.1 ± 2.6 kg cm−2, renal failure 15.2 ± 4.3 kg cm−2, diabetic control 11.4 ± 4.1 kg cm−2, and normal 8.2 ± 2.7 kg cm−2. A previous history of foot ulceration was recorded in 5 % of the diabetic control group, 10 % of patients with microalbuminuria and albuminuria, and 40 % with renal failure. We conclude that patients at all stages of diabetic nephropathy are at increased risk of non‐vascular foot ulceration.
Increased Erythrocyte Aldose Reductase Activity in Type 1 Diabetic Patients
Authors: Hamada Y. , Kito R. , Raskin P.
Published: July 2009

Elevated erythrocyte sorbitol levels have been demonstrated in diabetic patients. In order to explain the enhanced sorbitol formation, it has been suggested that aldose reductase might be activated by hyperglycaemia. Although aldose reductase activity has been reported to be increased in some tissues of diabetic patients, the effects of varying concentrations of glucose on the enzyme activity in vivo are unknown. To determine whether or not erythrocyte aldose reductase activity is increased in diabetic patients and is affected by glucose levels, we collected blood samples from 10 Type 1 diabetic patients while fasting and 2 h after a standard meal. We measured the activity of erythrocyte aldose reductase after partial purification by column chromatography. The results showed that erythrocyte aldose reductase activity was significantly increased in diabetic patients as compared with non‐diabetic subjects (7.3 ± 0.7 (±SE) vs 5.2 ± 0.3 u I‐erythrocytes−1, p<0.05). No correlation, however, was observed between fasting plasma glucose levels and the enzyme activity, and acute elevation of the blood glucose level did not affect the enzyme activity.
Do Rheological Variables Play a Role in Diabetic Peripheral Neuropathy?
Authors: MacRury S. M. , Lockhart J. C. , Small M. , Weir A. I. , MacCuish A. C. , Lowe G. D. O.
Published: July 2009

Whole blood viscosity and its determinants were measured in diabetic patients with and without peripheral neuropathy to assess whether these variables could have a role in the microvascular aetiology of diabetic peripheral neuropathy. Although corrected whole blood viscosity at high and low shear rates (5.29 ± 0.51 and 21.10 ± 3.03 mPa s), plasma viscosity (1.41 ± 0.13 mPa s), and red cell filtration ratio (0.49 ± 0.04) in diabetic patients were significantly different from non‐diabetic control subjects (high shear rate 4.83 ± 0.54, low shear rate 17.36 ± 2.78, plasma 1.29 ± 0.09 mPa s, all p < 0.001, and red cell filtration ratio 0.55 ± 0.03, p < 0.001) there were no significant differences between diabetic patients with neuropathy and those without. Blood rheology is altered to a similar extent in diabetic patients with and without neuropathy.
Urinary Growth Hormone Excretion During Puberty in Type 1 (Insulin‐dependent) Diabetes Mellitus
Authors: Hourd P. , Edge J.A. , Dunger D.B. , Dalton N. , Edwards R.
Published: July 2009

The excretion of urinary growth hormone was measured by a highly sensitive direct immunoradiometric assay in a cross‐sectional study during puberty in 70 children with Type 1 (insulin‐dependent) diabetes mellitus and 94 normal children. In normal children (n = 24) and diabetic children (n = 17) overnight urinary growth hormone excretion correlated significantly with the mean overnight plasma concentration (r = 0.70, p < 0.001, and r = 0.70, p < 0.001), indicating that urinary GH excretion reflects the circulating endogenous GH level. Overnight urinary growth hormone excretion increased during puberty. In normal and in diabetic children there was a peak in boys at genital stage 4 (both p < 0.01), and in girls at breast stage 2 (both p < 0.02). The diabetic children excreted more urinary growth hormone than the normal chidren at every pubertal stage. Excretion of albumin, retinol binding protein and N‐acetyl‐β‐D‐glucosaminidase was measured in urine from 38 diabetic children. Urinary growth hormone correlated weakly with urinary albumin (r = 0.49, p < 0.01), retinol binding protein (r = 0.42, p < 0.01), and N‐acetyl‐β‐D‐glucosaminidase (r = 0.43, p < 0.01). Urinary GH excretion was not related to blood glucose control (HbA1) in boys (n = 31) or girls (n = 39). The measurement of urinary growth hormone provides an assessment of endogenous growth hormone during puberty in normal and diabetic children. However, caution must be exercised in interpreting urinary growth hormone data from diabetic patients with increased excretion of albumin and retinol binding protein.
Reactive Hypoglycaemia in Association with Disordered Islet Function and Abnormal Hepatic Glucose‐6‐Phosphatase Activity: Response to Diazoxide
Authors: Pears J. , Jung R. T. , Browning M. C. K. , Taylor R. , Burchell A.
Published: July 2009

Severe reactive hypoglycaemia was confirmed in a non‐diabetic male patient by a counter‐regulatory hormone (GH, cortisol and catecholamine) response to profound hypoglycaemia induced by an intravenous glucose load. There was also evidence of disordered pancreatic islet cell paracrine regulation with hyperinsulinaemia and absent glucagon response to hypoglycaemia. A defect in the patient's hepatic glucose‐6‐phosphatase enzyme system was documented. Because of severe symptoms, dietary control was insufficient, but the patient responded clinically and biochemically to 18 months of oral diazoxide therapy. He also showed good biochemical response to a single dose (100 μg IM) of the somatostatin analogue octreotide.
Regulation of Non‐esterified Fatty Acid and Glycerol Concentration by Insulin in Normal Individuals and Patients with Type 2 Diabetes
Authors: Skowronski R. , Hollenbeck C. B. , Varasteh B. B. , Chen Y. ‐D. l. , Reaven G. M.
Published: July 2009

Plasma glycerol and non‐esterified fatty acid (NEFA) concentrations were determined in the basal state and in response to physiological hyperinsulinaemia in 30 non‐obese individuals, 15 with Type 2 diabetes and 15 with normal glucose tolerance. Patients with Type 2 diabetes had higher basal concentrations of both glycerol (81 ± 7 (± SE) vs 61 ± 7 μmol l−1, p<0.05) and NEFA (842 ± 40 vs 630 ± 46 μmol l−1, p<0.002). Plasma NEFA and glycerol concentrations fell in both groups when steady‐state plasma insulin concentrations were raised to approximately 450 pmol l−1 by an infusion of exogenous insulin, but plasma concentrations of glycerol (28 ± 3 vs 13 ± 3 μmol l−1, p<0.002) and NEFA (186 ± 15 vs 109 ± 14 μmol l−1, p<0.001) were still higher in patients with Type 2 diabetes. Percentage decrease in glycerol from basal levels in response to insulin was significantly less in patients with Type 2 diabetes than in control subjects (64 ± 3 vs 80 ± 3 %, p<0.005); percentage decrease in plasma NEFA concentration was similar in the two groups (78 ± 3 vs 80 ± 4 %). These results suggest that both plasma glycerol and NEFA concentrations are higher than normal in patients with Type 2 diabetes when measured at the same insulin concentration, both under basal conditions and in response to physiological hyperinsulinaemia. However, in patients with Type 2 diabetes the percentage decrease in plasma glycerol concentration was significantly less than the percentage decrease in NEFA concentration (64 ± 3 vs 78 ± 3 %, p<0.001).