bluuebunny/crossref_metadata_2025 huggingface dataset:
Pain Relief in Diabetic Neuropathy: The Effectiveness of Imipramine and Related Drugs
Authors: Young R. J. , Clarke B. F.
Published: July 2009

Experience of treating 80 consecutive patients with painful diabetic neuropathy and a double‐blind study of imipramine in acute painful neuropathy are reported. A standard stepwise protocol was used, based on imipramine as the drug of first choice, substitution of amitriptyline or mianserin as second choice, and, thirdly, addition of phenothiazine or clonazepam if necessary. Sixty per cent were satisfied with imipramine alone and all but 3 (5%) were improved by the stepwise scheme. Paradoxically, the most effective analgesia was obtained in those with the most severe and unpleasant pain. Often 150 mg of imipramine or amitriptyline was necessary. The onset of analgesia and relapse after withdrawal of treatment were rapid, facilitating clinical use, and suggesting a peripheral rather than central drug action.
Plasma Glucose Responses to Glucose, Sucrose, and Honey in Patients with Diabetes Mellitus: An Analysis of Glycaemic and Peak Incremental Indices
Authors: Samanta A. , Burden A. C. , Jones A. R.
Published: July 2009

We have studied the hyperglycaemic effect of the carbohydrate of glucose, sucrose, and honey equivalent to 20g in twelve normal volunteers, eight patients with insulin‐dependent diabetes mellitus (IDDM), and six patients with non‐insulin‐dependent diabetes mellitus (NIDDM). Honey produced an attenuated postprandial glycaemic response in normal volunteers (vs glucose p<0.005; vs sucrose p<0.05) and IDDMs (vs glucose p<0.005; vs sucrose p<0.05). The glycaemic index (GI) showed considerable variability within each subject group. Combined with a peak incremental index (PI), the two indices appear to be more valuable in predicting the glycaemic effects of carbohydrates rather than either one alone. We suggest that honey may prove to be a valuable sugar substitute in diabetics, and that both the GI and PI should be used in the analysis of food.
Potentiation of Hypotensive Effect of Debrisoquine by Insulin
Authors: Hume L.
Published: July 2009

A 36‐year‐old man who had been an insulin‐dependent diabetic for 27 years developed severe postural hypotension only when taking debrisoquine and a short‐acting insulin. Hourly recordings of lying and standing blood pressure after an oral dose of debrisoquine in the presence and absence of short‐acting insulin confirmed an interaction between the drugs causing symptoms of postural hypotension which may be confused with hypoglycaemia.
Vertebral and Paravertebral Sepsis in Diabetes: An Easily Missed Cause of Backache
Authors: Baldwin N. , Scott A. R. , Heller S. R. , O'Donoghue D. , Tattersall R. B.
Published: July 2009

Vertebral osteomyelitis and epidural abscess are uncommon causes of backache but may have a prediliction for patients with diabetes. We report four cases seen in a diabetic unit over 2 years to emphasize the importance of making a diagnosis as early as possible. We suggest that when a diabetic patient complains of backache the erythrocyte sedimentation rate should be measured since this is the best clue that backache is due to something other than a mechanical derangement.
Necrotizing Fasciitis: A Potentially Fatal Complication of Diabetes Mellitus
Authors: Silberberg E. M. , Bodansky H. J.
Published: July 2009

We describe a fatal case of necrotizing fasciitis in a newly diagnosed 73‐year‐old diabetic patient. This rare condition which has been described previously in diabetic patients, is characterized by widespread necrosis of underlying fascial tissue associated with severe systemic upset, despite few overt cutaneous manifestations. Without prompt recognition and extensive debridement it may be fatal.
Insulin Oedema and its Clinical Significance: Metabolic Studies in Three Cases
Authors: Wheatley T. , Edwards O. M.
Published: July 2009

Three patients with insulin‐dependent diabetes mellitus are described in whom generalized oedema and weight gain followed the administration of excessive monocomponent insulins, in two cases associated with symptomatic hypoglycaemia. Serial measurements of plasma volume and transcapillary escape rate of albumin (TERA) using 125I‐labelled albumin, serum colloid osmotic pressure (COP) using a membrane colloid osmometer, packed cell volume (PCV), and serum proteins, showed that oedema was associated with an increased plasma volume and TERA, while serum albumin and total protein concentration and serum COP were reduced. A reduction in daily insulin dose abolished hypoglycaemia and resulted in weight loss, natriuresis, diuresis, a reduction in plasma volume and TERA, and an increase in serum albumin, total protein, and COP.

Strict metabolic control in previously poorly controlled patients may cause insulin‐induced increments in plasma volume and albumin escape rate.
Defective Non‐insulin‐mediated and Insulin‐mediated Glucose Transport and Metabolism in Adipocytes from Obese and Lean Patients with Untreated Type 2 Diabetes Mellitus
Authors: Hjøllund E. , Beck‐Nielsen H. , Pedersen O. , Richelsen B. , Sørensen N. Schwartz
Published: July 2009

Insulin binding, glucose transport, and glucose metabolism were investigated in isolated adipocytes from 11 lean and 13 obese patients with non‐insulin‐dependent diabetes mellitus. Insulin binding at 15°C was reduced by 35% (p<0.01) in both lean and obese diabetic patients, whereas insulin binding (or uptake) at 37°C was similar in diabetic patients and healthy controls. In lean diabetic patients both non‐insulin‐mediated (basal) and maximally insulin‐stimulated glucose transport and metabolism were significantly reduced (all p<0.01). The percentage responses to insulin were also markedly reduced (p<0.05, p<0.02). In obese diabetic patients basal glucose transport was reduced (p<0.01) but basal glucose metabolism was not. Insulin‐stimulated glucose transport and metabolism were significantly reduced (p<0.01, p<0.05). The percentage responses were reduced compared to healthy controls (p<0.05, p<0.05) but higher than in lean diabetic patients (p<0.05).

We conclude that adipocytes isolated from both lean and obese patients with non‐insulin‐dependent diabetes mellitus are characterized by severely depressed non‐insulin‐mediated and insulin‐mediated glucose transport and depressed insulin‐mediated glucose metabolism. The major defect seems to be a reduced maximal effect of insulin on glucose metabolism, suggesting post‐binding and post‐transport abnormalities.
Treatment of Diabetic Gastroparesis with Oral Domperidone
Authors: Watts G. F. , Armitage M. , Sinclair J. , Hill R. D.
Published: July 2009

Three patients with severe diabetic gastroparesis unresponsive to metoclopramide were found to have markedly prolonged gastric half‐emptying times (t1/2) using a radionuclide‐labelled test meal. They all showed symptomatic improvement and normal t1/2 within one week of taking oral domperidone 10 mg q.d.s. Oral domperidone may have a role in the treatment of severe diabetic gastroparesis particularly in metoclopramide‐resistant cases.
A Multiple Injection Regimen using an Insulin Injection Pen and Pre‐filled Cartridged Soluble Human Insulin in Adolescents with Diabetes
Authors: Jefferson I. G. , Marteau T. M. , Smith M. A. , Baum J. D.
Published: July 2009

A multiple insulin injection regimen using a self‐contained injection device Novopen® (Novo Industries, Bagsvaerd, Copenhagen, Denmark) was assessed in 11 adolescents (age range 12.1–16.9 years) with diabetes. Ten patients completed the 3‐month study period and eight expressed a wish to continue with the regimen, finding that the advantages it offered out‐weighed the inconvenience of multiple injections. Mean glycosylated haemoglobin fell over the 3 months of the study period from 13.7±2.7% to 11.7±3.4% (NS) and there was a trend towards lower mean blood values which reached significance at the pre‐lunch measurement (p<0.02).
Experience With NovoPen®, an Injection Device using Cartridged Insulin, for Diabetic Patients
Authors: Walters D. P. , Smith P. A. , Marteau T. M. , Brimble A. , Borthwick L. J.
Published: July 2009

An insulin injection device, NovoPen®, incorporating cartridged U100 Human Actrapid insulin was used in a group of 31 insulin‐dependent diabetic patients aged 31.4±11.2 years (mean±S.D.; range 16.5–57.0) to assess its acceptance and suitability in a regimen involving an injection before each of their three main meals plus an evening injection of Human Monotard® insulin from a conventional syringe.

Twenty‐seven patients completed 48 weeks of NovoPen® therapy and preferred to continue with the multiple injection regimen in the long term. The device was well accepted and may make multiple injection regimens more feasible.
Long‐term Survival of Human Fetal Pancreatic Tissue Transplanted into an Insulin‐dependent Diabetic Patient
Authors: Tuch B. E. , Sheil A. G. R. , Ng A. B. P. , Turtle J. R.
Published: July 2009

The explants of two human fetal pancreases of 15 weeks gestational age were cultured for 6–7 days before being implanted in a 29‐year‐old insulin‐dependent diabetic woman who had received a renal graft two months previously. One pancreas was placed in the flexor muscles of the forearm whilst the other was implanted in an omental pouch. To reduce the chances of rejection the tissue was cultured in vitro, the donor of the tissue placed in the forearm was DR antigen matched with the recipient and the patient remained on cyclosporin and prednisone therapy. At 3 months a mass developed in the forearm muscle at the site of transplantation, and continued to grow. Biopsy at 13 months showed a small area of original pancreas surrounded by a large collection of mature lymphocytes and fibrous tissue. A and D cells could be seen around pancreatic ducts but B cells and acinar tissue were absent. At no stage during follow‐up was plasma C‐peptide detected in the recipient.
A Comparison of Biosynthetic Human Insulin with Porcine Insulin in the Blood Glucose Control of Diabetic Pregnancy
Authors: Leiper J. M. , Paterson K. R. , Lunan C. B. , MacCuish A. C.
Published: July 2009

Fifty insulin‐dependent pregnant diabetic women were treated from presentation at the antenatal clinic with a regimen of either porcine or biosynthetic human soluble and isophane insulins. Blood glucose values, glycosylated haemoglobin, insulin requirements and outcome of pregnancy were compared in the two groups of patients. No difference was noted in blood glucose control, birth weight or neonatal complications. In the group treated with human insulin, fasting blood glucose could only be controlled by significantly greater doses of human isophane insulin injected before the evening meal. Furthermore, in two cases adequate glycaemic control required the injection of the evening human isophane insulin to be delayed until bedtime.
Beneficial Effect of Glycaemic Improvement in Non‐ischaemic Forms of Diabetic Retinopathy: A 3‐Year Follow‐up
Authors: Selam J. L. , Millet P. , Zaluski S. , Saeidi S. , Mirouze J.
Published: July 2009

Recent studies have suggested that optimal glucose control fails to arrest or even worsens background retinopathy possibly by aggravating retinal ischaemia. Fourteen insulin‐dependent diabetic patients, aged 34±11 years (mean ± SD) treated by long‐term intraperitoneal insulin infusion using portable pumps, were followed for 3 years. Preproliferative or proliferative lesions on ophthalmoscopy and large non‐perfused areas on fluorescein angiography were exclusion criteria. Six patients were found to have minimal and 8 mild background retinopathy. The patients were retrospectively assigned to two comparable groups except for their glycaemic equilibrium under insulin infusion: average control (n=6) and excellent control (n=8), although glycaemic control was significantly improved in all cases when compared to previous conventional therapy. Fluorescein changes were scored blindly and independently by 3 ophthalmologists according to modifications of fluorescein diffusion and capillary abnormalities. The two types of retinal lesions improved gradually in 10 patients and deteriorated in only 1 patient, although not progressing to proliferative retinopathy. Structural improvements were significantly more frequent in the excellently controlled group.

We conclude that non‐ischaemic lesions may still be arrested and even improved by tight metabolic control.
C‐peptide Levels in Transient Neonatal Diabetes
Authors: Halliday H. L. , Reid M. McC. , Hadden D. R.
Published: July 2009

A baby boy with transient neonatal diabetes mellitus presenting with hyperglycaemia, glycosuria, and dehydration without ketonuria on the second day of life is reported. C‐peptide levels were measured to aid in the assessment of insulin treatment. Very low levels were found for the first 5 months of life (<0.06 nmol/l). Thereafter insulin treatment was discontinued and the baby thrived showing normal growth and development at age 2 1/2 years.
Long‐Term Effects of Intestinal Alpha‐Glucosidase Inhibition on Postprandial Glucose, Pancreatic and Gut Hormone Responses and Fasting Serum Lipids in Diabetics on Sulphonylureas
Authors: Uttenthal L. O. , Ukponmwan O. O. , Wood S. M. , Ghiglione M. , Ghatei M. A. , Trayner I. M. , Bloom S. R.
Published: July 2009

Seventeen non‐insulin‐dependent diabetics poorly controlled by diet and sulphonylurea drugs took part in a long‐term (20–52 weeks) trial of the effect of an alpha‐glucosidase inhibitor (acarbose 100 mg thrice daily) on postprandial glycaemic and gastro‐entero‐pancreatic hormone responses. Patients were assessed before, during, and after the trial period with identical 2.2 MJ mixed test meals plus placebo or acarbose 100 mg, and sulphonylurea therapy was continued throughout. Acarbose administration reduced the integrated postprandial plasma responses of glucose to 58 ± 10% (mean ± SEM, p < 0.001), insulin to 61 ± 10% (p < 0.01) and gastric inhibitory polypeptide to 45 ± 8% (p < 0.001) of control values, increased the enteroglucagon response to 152 ± 26% (p < 0.001) of control and slightly prolonged the postprandial release of motilin. Recorded glycosuria was significantly (p < 0.01) reduced throughout the treatment period. The effects of acarbose on postprandial glycaemic and endocrine responses remained approximately constant throughout the trial period, and responses returned to pre‐treatment values within 2 days of stopping treatment.
Evaluation of Four Modern Home Blood Glucose Meters Including Two Memory Meters
Authors: Petranyi G. , Kyne D. A. , Alberti K. G. M. M.
Published: July 2009

Four battery‐operated blood glucose reflectance meters have been tested for precision, accuracy, and convenience of use. Parallel assays on 50 venous blood samples comparing a meter and a glucose oxidase reference method gave the following regression line parameters and correlation coefficients: Diatron Easytest (Eastlords Electronics Ltd), y = 0.76x + 1.23, r = 0.93; Glucochek II (Medistron Ltd), y = 0.90x − 0.01, r = 0.98; Hypocount MX (Hypoguard Ltd), y = 0.97x − 0.14, r = 0.98; Reflolux (Boehringer Mannheim GmbH), y = 0.97x + 0.18, r = 0.99. Reflolux has to be recalibrated with a barcoded film strip for each new test strip tin and is the most precise and accurate meter. Glucochek II using both whole and half BM Test Glycemie 20‐800R test strips, showed similarly good precision, and was the simplest meter to use containing only one moving operational part. Hypocount MX is the smallest of these meters, is easy to use and has a memory which can store up to 10 blood glucose readings. The memory of the Diatron Easytest is bigger and easier to use since it stores and automatically updates 25 successive glucose values; however, this was the least accurate and least precise of the meters.
Diabetic Control is Improved by Guar Gum and Wheat Bran Supplementation
Authors: Vaaler S. , Hanssen K. F. , Dahl‐Jørgensen K. , Frølich W. , Aaseth J. , ødegaard B. , AagenaE ø.
Published: July 2009

Twenty‐eight insulin‐dependent diabetics were treated with different dietary regimes for three periods of three months. Initially they used a white flour bread (run‐in period), then their daily bread ration was enriched with guar gum (mean dose: 29g), and then with wheat bran (mean dose: 33g) in a randomized crossover pattern. Fasting and postprandial blood glucose levels were measured on filter paper spots collected once weekly at home, and other biochemical values were measured monthly. No improvement in diabetic control was seen during the run‐in period. Mean postprandial blood glucose decreased from 12.0 ± 3.8 mmol/l (mean ± SD) in the run‐in period to 9.7 ± 2.8 mmol/l (p<0.01) in the guar period and to 9.7 ± 2.7 mmol/l (p<0.01) in the bran period. HbA1 decreased from 10.5 ± 2.1% in the run‐in period to 9.7 ± 1.6% (<0.05) at the end of the guar period and 9.9 ± 1.2% (not significant) at the end of the bran period. Only modest changes were seen in serum‐lipids ‐ total cholesterol decreased significantly in the guar period, but not in the bran period. In this study both guar gum and wheat bran were well tolerated and produced a substantial decrease in postprandial blood glucose.
Diabetes and Autonomic Neuropathy: An Immunological Association?
Authors: Gilbey S. G. , Guy R. J. C. , Jones H. , Vergani D. , Watkins P. J.
Published: July 2009

Lymphocytic infiltration of autonomic ganglia found at autopsy and a strong clinical association with iritis suggests that diabetic autonomic neuropathy might have an immunological basis. We measured levels of circulating immune complexes, complement (C3, C4), complement breakdown products (C3d), and insulin antibodies in diabetics with autonomic neuropathy and a history of iritis (n = 17), compared to diabetics of similar age and duration with autonomic neuropathy but no history of iritis (n = 20), and with uncomplicated insulin‐dependent diabetics (n = 23), together with normal controls (n = 26). We found higher levels of circulating immune complexes in patients with autonomic neuropathy (irrespective of iritis) compared to normal controls, and differences in C3d levels suggesting complement activation. C4 levels were unexpectedly normal in the diabetics with autonomic neuropathy, in contrast to the uncomplicated insulin‐dependent diabetic controls. Insulin antibody levels showed no difference between the three groups of diabetics. These findings suggest that immunological mechanisms may be implicated in the aetiology of diabetic autonomic neuropathy and that further studies are indicated.
Dietary Carbohydrate Deficits and Hypoglycaemia in the Young Diabetic on Holiday
Authors: Frost G. J. , Hodges S. , Swift P. G. F.
Published: July 2009

On two British Diabetic Association Educational Holidays, 67 children aged 6–9 years had their diabetic management analysed and hypoglycaemic episodes recorded. The average pre‐camp carbohydrate prescription of the children was found to be 44 g below minimal recommended values. Hypoglycaemic episodes were more frequent in those with greater carbohydrate deficits and morning insulin doses in excess of 0.7 U/kg. The management of the young diabetic at camp should include a pre‐camp analysis with appropriate adjustment of diet and insulin to minimize hypoglycaemic crises. Guideline figures are proposed for average age‐related carbohydrate intake.
Fatal Rhinocerebral Mucormycosis in a Newly Diagnosed Diabetic
Authors: Larkin J. G. , Butcher I. G. , Frier B. M. , Brebner H.
Published: July 2009

A 48‐year‐old male developed fever and sore throat while in Spain and was admitted to hospital, dehydrated, ketotic, pyrexial, and with a blood glucose of 35 mmol/l. Despite treatment with intravenous fluids, insulin, cephalosporin, potassium and bicarbonate he returned to Britain 7 days later, underhydrated and acidotic, though euglycaemic. His face was discoloured, there was painless nasal and maxillary swelling, oral candidiasis, and he went on to develop ophthalmop‐legia and sudden blindness. Staphylococcus albus and mycelial fungus were isolated, the latter was identified as Mucor hiemalis, but despite treatment with amphotericin B co‐ordinated with radical maxillary‐facial surgery he died 31 days after the initial symptoms. Rhinocerebral mucormycosis is a recognized complication of ketoacidosis which is rarely reported in the UK. The organism invades arteries aggressively, therefore radical therapy must be started early to prevent the high mortality.
Childhood Diabetes Mellitus in Ethiopians
Authors: Lester F. T.
Published: July 2009

Of 1088 consecutive Ethiopian diabetic patients registered over 9 years 80 (7.4%) were diagnosed at or before age 15 years. There were 48 girls and 32 boys, with mean age of onset of 10.1 years. Diabetes had been present 10 years or less in 62, 11 to 20 years in 15, and more than 20 years in only 2. Twenty‐two were rural, 27 had poverty certificates. Twenty‐three have known diabetic relatives. The original mode of presentation could not be verified in 16, 7 presented in ketoacidosis, 5 were diagnosed by a diabetic relative, and the rest presented with the rapid onset of classical symptoms. To date, 43 have been ketoacidotic at least once. No pancreatic calcification was seen in 34 abdominal radiographs. Three of 6 newly diagnosed patients tested had islet cell surface antibodies. Three cases, intially suggestive of ‘tropical malnutrition diabetes’, evolved into typical type 1 diabetes. Serious complicating illnesses were tuberculosis (6), bacterial endocarditis (1) and rhinocerebral mucormycosis (1). Six patients have had metabolic cataracts. Ten patients (12%) have died, 4 of ketoacidosis and 4 of diabetic nephropathy. Childhood diabetes mellitus in Ethiopians is clinically very similar to type 1 diabetes elsewhere.
Hypotensive Therapy Reduces Microvascular Albumin Leakage in Insulin‐dependent Diabetic Patients with Nephropathy
Authors: Parving H.‐H. , Smidt U. M.
Published: July 2009

The effect of hypotensive therapy on the transcapillary escape rate of albumin (TERalb) was studied in eight hypertensive insulin‐dependent diabetic patients (mean age 29, range 19–42 years) with nephropathy and retinopathy. Transcapillary escape rate of albumin (initial disappearance of intravenously injected 125l‐labelled human serum albumin), urinary albumin excretion rate (radial immunodiffusion), and glomerular filtrate rate (single bolus 51‐Cr‐EDTA technique) were measured. After hypotensive treatment (mean duration, 23 months, range 7–39 months) with combinations of metoprolol, hydralazine, and frusemide or thiazide diuretics, arterial blood pressure fell from 152/103 ± 18/6 mmHg (mean ± SD) to 133/81 ± 12/10 mmHg (p<0.01), transcapillary escape rate of albumin from 10.2 ± 1.8 to 8.1 ± 1.8% of intravascular mass of albumin/h (p0.01), albuminuria from 1803 (370–5066) μ/min to 940 (101–2676) μg/min (median and range, p<0.05), and glomerular filtration rate from 103 ± 23 to 84 ± 22 ml/min/1.73 m2 (p<0.01).

Our study suggests that effective hypotensive treatment reduces the abnormally elevated albumin leakage characteristically found in insulin‐dependent diabetic patients with clinical microangiopathy. This may be due to a reduction in the hydrostatic pressure in the microcirculation.
Comparison of Liquid Phase Radiobinding Assay and Solid Phase ELISA for the Measurement of Insulin Antibodies and Insulin Autoantibodies in Serum
Authors: Diaz J.‐L. , Wilkin T.
Published: July 2009

Sera containing insulin antibodies from 20 insulin‐treated diabetic patients, sera containing insulin autoantibodies from 20 insulin‐naive non‐diabetic patients, and from 10 normal controls, were tested at 1:20 dilution in three different radioimmunoassays (RIA) and an enzyme linked immunosorbent assay (ELISA), using a highly purified human insulin ligand. The RIA using insulin radiolabelled at multiple sites detected insulin antibodies in 17/20 and insulin autoantibodies in 13/20 sera. The same RIA using A‐14‐monoiodinated insulin was sensitive to antibodies and autoantibodies in all the sera. The same RIA using sera after insulin extraction detected only 13/20 diabetic sera and 9/20 autoimmune sera as positive, owing to a substantial rise in non‐specific binding of the control sera. ELISA was sensitive to insulin antibodies and autoantibodies in every case. When binding curves for ELISA and the most sensitive RIA were compared using serial dilutions of four insulin antibody containing sera and four insulin autoantibody containing sera, antibody titres varied from 1.1 to 3.8 times higher in ELISA, and autoantibody titres from 10.6 to 28.6 times higher in ELISA. These studies indicate that ELISA is more sensitive than RIA to insulin antibodies, and in particular to insulin autoantibodies.
Altered Recognition of Hypoglycaemic Symptoms in Type I Diabetes during Intensified Control with Continuous Subcutaneous Insulin Infusion
Authors: Lager I. , Attvall S. , Blohmé G. , Smith U.
Published: July 2009

The effect of intensified metabolic control obtained with continuous subcutaneous insulin infusion (CSII) on the frequency and symptoms of hypoglycaemia was studied in type I diabetic patients. The reproducibility of the questionnaire used to evaluate the hypoglycaemic symptoms was verified in a control group receiving unchanged conventional insulin therapy for 2 months. Metabolic control was significantly improved during CSII (HbA1c 6.8 ± 0.4% versus 8.7 ± 0.7%, normal range up to 5.4%) in all patients while no change was seen in the control group. The results of frequent self glucose monitoring showed that the incidence of low glucose levels (below 3.5 mmol/l) increased about threefold in the CSII group. Awareness of hypoglycaemia was clearly changed during CSII with less pronounced adrenergic symptoms while no alterations were found in the group with unchanged metabolic control. These results emphasize the importance of regular self glucose monitoring during CSII and of informing the patients that their hypoglycaemic symptoms may change during intensified control.
Human, Porcine and Bovine Ultralente Insulin: Subcutaneous Administration in Normal Man
Authors: Owens D. R. , Vora J. P. , Heding L. g. , Luzio S. , Ryder R. E. J. , Atiea J. , Hayes T. M.
Published: July 2009

Six normal subjects received subcutaneous human, porcine, and bovine ultralente insulin (0.30 U/kg) and diluent (control) in randomized order. Plasma glucose, C‐peptide, and insulin were measured for 32 h after injection. From 10 h onward human ultralente produced significantly lower plasma glucose levels (p<0.05‐0.01) compared to bovine ultralente. Porcine ultralente produced an intermediate hypoglycaemic response up to 16 h and was similar to the bovine insulin from 24–32 h. Estimated exogenous insulin concentration was higher (p<0.05‐0.001) following human ultralente compared to bovine ultralente between 2 and 22 h after injection. Up to 24 h the porcine preparation led to intermediate insulin levels, but becoming identical to bovine ultralente from 28–32 h. Peak mean exogenous insulin values for human, porcine, and bovine ultralente were 0.054, 0.044, and 0.023 nmol/l at 14, 16, and 18 h, respectively, reaching 0.022, 0.013, and 0.013 nmol/l at 32 h. The different pharmacokinetic behaviour of human and bovine ultralente insulin must be considered when initiating treatment with human ultralente or transferring patients from bovine to human ultralente.
Impaired Vibratory Perception and Diabetic Foot Ulceration
Authors: Boulton A. J. M. , Kubrusly D. B. , Bowker J. H. , Gadia M. T. , Quintero L. , Becker D. M. , Skyler J. S. , Sosenko J. M.
Published: July 2009

We have studied risk factors for diabetic foot ulceration by comparing diabetic patients who had active foot ulcers (n = 86) with diabetic patients who had no history of foot ulcers (n = 49). Whereas there was a strong association of diabetic foot ulceration with abnormal vibratory perception (Odds Ratio = 10.77; p < 0.001, which increased with worsening vibratory perception), there was little association with abnormality of the ankle‐pressure index (Odds Ratio = 2.84, p = n.s.). Although foot ulceration and limited joint mobility were associated (Odds Ratio = 3.57, p < 0.001), this relation was not significant when allowances for abnormal vibratory perception and diabetes duration were made. These data suggest that sensory neuropathy is of greater aetiological importance than peripheral vascular disease in the development of diabetic foot ulceration. The measurement of the vibratory perception threshold is clinically useful in identifying those diabetic patients at high risk of foot ulceration.
Reactions to Educational Techniques: Coping Strategies for Diabetes and Learning
Authors: Dunn Stewart M
Published: July 2009

Book reviewed in this article:

Based on a review presented at the Annual Conference of the Education Section, British Diabetic Association, London, 8th February, 1986.
Behaviour Therapy for Phobia of Venepuncture
Authors: Steel J. , Taylor R. , Lloyd C.
Published: July 2009

A 28‐year‐old female insulin‐dependent diabetic patient developed a severe phobia to venepuncture which seriously interfered with her medical treatment. A two‐month course of behaviour therapy successfully alleviated the phobia.
A Pragmatic Approach to Sexual Dysfunction in Diabetic Men: Psychosexual Counselling
Authors: McCulloch D. K. , Hosking D. J. , Tobert A.
Published: July 2009

In order to avoid the problems inherent in the assessment of any organic component of impotence, a consecutive series of 20 diabetics were treated with psychotherapy after a detailed assessment of the psychological components of their disability. Only three patients improved in the long term and responders could not be identified from pretreatment characteristics. However, most of the patients had been impotent for several years and their successful adaptation may have limited the success of psychotherapy. There is a need to identify the impotent patient at an early stage in order to offer more effective treatment. This might also avoid the problems of adaptation and the need for detailed investigations of pelvic nervous and vascular function.
Exercise‐induced Hypoglycaemia and Subcutaneous Insulin Infusion
Authors: Edelmann Edmund , Staudner Veronika , Bachmann Werner , Walter Helmut , Haas Wolfgang , Mehnert Helmut
Published: July 2009

To assess whether exercise‐induced hypoglycaemia could be prevented by interruption of insulin infusion (3 h) we studied diabetic patients treated with continuous subcutaneous insulin infusion (CSII). The studies were performed in 7 insulin‐dependent diabetics (aged 31.4 ± 4.8 (mean ± SD) years, duration of diabetes 16.9 ± 5.4 years), after an overnight fast and in the afternoon, 4 h after the last pre‐meal bolus injection (exercise and control period). Bicycle exercise (45 min at 60% of maximum oxygen consumption) was started 30 min after the insulin infusion was stopped. During exercise there was a more pronounced decline in blood glucose in the afternoon (2.2 ± 0.3 mmol/l, mean ± SEM) than in the morning (1.4 ± 0.4 mmol/l) (p<0.01). This corresponded to higher mean levels of free insulin during exercise in the afternoon (20 ± 4.5 mU/l vs 12.0 ± 1.0 mU/l, in the morning). Interruption of insulin delivery for 3 h resulted in a moderate increase of blood glucose, a gradual decrease of free insulin, and a moderate increase in free fatty acids and ß‐hydroxybutyrate. During exercise in the afternoon 3 diabetics suffered from symptomatic hypoglycaemia (BG <2.8 mmol/l). In contrast with most of the other patients they showed no decline of free insulin during exercise. Thus even after interruption of basal rate insulin infusion moderate postprandial exercise may lead to hypoglycaemia if there is relative hyperinsulinism.
Ambulatory Monitoring of the ST Segment in Diabetic Men With and Without Peripheral Neuropathy
Authors: Hume L. , Oakley G. D. G. , Boulton A. J. M. , Peach M. , Hardisty C. A. , Ward J. D.
Published: July 2009

To assess whether myocardial ischaemia is more common in diabetic patients with neuropathy, 24‐hour ambulatory monitoring of the ST segment was performed on 27 diabetic men without peripheral neuropathy and in 28 with neuropathy. The patients were matched for age 54 ± 7 years (mean ± SD) versus 54 ± 7 years and for duration of diabetes (16 ± 9 years versus 16 ± 12 years). None had clinical evidence of heart disease.

Episodes of ST segment depression were seen during ambulatory monitoring in 12 diabetics (22%) but were not more common in patients with peripheral neuropathy. Four of the 13 diabetics with autonomic neuropathy had ST depression during ambulatory monitoring. During a median follow‐up period of 50 months, four patients developed clinical heart disease. Three of these patients had shown ST depression during ambulatory monitoring.

ST depression during ambulatory monitoring is common in diabetic men without cardiac symptoms but is not related to the presence of peripheral neuropathy. Diabetics with ST depression during ambulatory monitoring are at increased risk of developing heart disease in subsequent years.
Nine Years' Personal Experience of Intensified Diabetes Control: Infusion versus Injections
Authors: Jarratt A. M.
Published: July 2009

The author, who had been an unstable diabetic since 1948, has attempted to maintain normoglycaemia since January 1977 after developing retinopathy and painful peripheral neuropathy. After 40 months of intensified conventional therapy (ICT), blood glucose fell from 13.0 ± 2.0 (mean ± S.D.) to 8.6 ± 1.5 mmol/l (p<0.001), but with 36% of blood glucose tests still exceeding 10.0 mmol/l. After 6 years of continuous subcutaneous insulin infusion (CSII) mean blood glucose was 6.6 ± 0.7 mmol/l (p<0.001) CSII/ICT, with only 10% of tests exceeding 10 mmol/l, smoother glycaemic profiles and excellent control overnight with no hypoglycaemia. These improvements under CSII were attributed to continuous varied insulin intake, which was instantly and unobtrusively adjustable, and more reliable food/insulin/blood glucose relationships. No infusion‐site abscesses or serious ketoacidosis developed.

Under both therapies glycaemic control was readily disrupted by exercise, minor dietary inaccuracies, relaxing of vigilance and unknown factors. Whenever the sense of commitment faultered there was a tendancy to maintain higher glycaemic values to avoid distressing hypoglycaemia. Over the nine years, retinopathy progressed, foot pains regressed slightly but no fresh complications developed. Thus, intensified conventional management alone improved control, but CSII enabled the author to remain near‐normoglycaemic for years (given sufficient motivation), with a less regimented lifestyle.
Neutrophil Sorbitol Production Impairs Oxidative Killing in Diabetes
Authors: Wilson R. M. , Tomlinson D. R. , Reeves W. G.
Published: July 2009

The mechanism whereby hyperglycaemia inhibits neutrophil function is unclear. We have examined neutrophil killing of Candida albicans in the presence of increased concentrations of glucose and galactose. Killing was abolished in 50 mmol/l glucose and 10 and 50 mmol/l galactose. The oxidative phase of killing was examined using lucigenin‐enhanced chemiluminescence. An increase in glucose concentration from 5 to 50 mmol/l produced a fall in chemiluminescence ouptut from 128.5 ± 16.8 (mean ± SE) to 82.2 ± 9.8 mVmin (a reduction of 36%). These data suggest the existence of aldose reductase activity in neutrophils and using gas chromatography we have demonstrated the presence of sorbitol in extracts of diabetic neutrophils. As oxidative killing and sorbitol production are both NADPH‐dependent the inhibition of killing is likely to be due to competition for this electron donor. This abnormality of neutrophil function may aggravate various infections in the patient with diabetes.
Standing to Lying Heart Rate Variation. A New Simple Test in the Diagnosis of Diabetic Autonomic Neuropathy
Authors: Bellavere F. , Cardone C. , Ferri M. , Guarini L. , Piccoli A. , Fedele D.
Published: July 2009

We have examined the immediate heart‐rate response to standing to lying (S‐L) in 83 male insulin‐dependent diabetic subjects aged 40 ± 11 years (mean ± S.D.) who underwent five other cardiovascular autonomic tests. Using a specially devised scoring system, the patients were divided into 3 groups: (1) 54 subjects without autonomic neuropathy; (2) 17 ‘borderlines’; (3) 12 with autonomic neuropathy. The results were compared with those of 50 sex and age matched controls. We evaluated: S‐L1 = ratio between R‐R mean before lying and R‐R minimum over the first 5 beats after lying; S‐L2 = ratio between R‐R maximum between the 20th to 25th beat and R‐R minimum over the first 5 beats after lying. In controls S‐L1 was 1.23 ± 0.098 (mean ± S.D.), S‐L2 1.56 ± 0.2. In diabetic subjects without autonomic neuropathy S‐L1 was 1.18 ± 0.096 (p<0.01), S‐L2 1.50 ± 0.23. In the autonomic group S‐L1 was 1.03 ± 0.01 (p<0.001), S‐L2 1.16 ± 0.086 (p<0.001). We propose that the lowest normal and highest abnormal limits of S‐L1 are 1.10 and 1.07, respectively, and that normal and highest abnormal limits of S‐L2 are 1.23 and 1.14, respectively. We suggest the use of S‐L1 as a pure parasympathetic test and S‐L2 as a mixed but predominantly sympathetic test in the diagnosis of autonomic neuropathy.
Intestinal Permeability in Diabetic Diarrhoea
Authors: Cooper B. T. , Ukabam S. O. , O'Brien I. A. D. , Hare J. P. O. , Corrall R. J. M.
Published: July 2009

Small intestinal permeability to mannitol and lactulose was studied in 12 patients aged 36–70 (mean 56) years with diabetic diarrhoea (DD). Ten uncomplicated diabetics aged 24–56 (mean 37) years and 25 normal subjects aged 22–60 (mean 37) years served as controls. Permeability was assessed by measuring urinary recovery of the test substances after oral ingestion. Mean mannitol excretion in patients with DD was significantly lower than in normal controls but was not significantly different from the uncomplicated diabetics. Mean lactulose excretion was not significantly different in the three groups. However, lactulose to mannitol excretion ratios (LMER) were significantly higher in patients with DD compared to the controls or the uncomplicated diabetics. LMER in seven patients with DD were outside the normal range. LMER in patients with DD did not correlate with blood urea, small intestinal transit time, faecal fat excretion, small intestinal bacterial overgrowth, duration of diabetes or duration of diarrhoea. Jejunal morphology was normal in all patients with DD. It was concluded that small intestinal permeability was abnormal in some patients with DD and that this might be a factor in the aetiology of the diarrhoea.
Compliant Behaviour: Relationship to Attitudes and Control in Diabetic Patients
Authors: Lockington T. J. , Meadows K. A. , Wise P. H.
Published: July 2009

A study was conducted to examine patient performance of certain safety measures in relation to ‘attitude’ and glycaemic control. One hundred and thirty consecutive routinely attending insulin‐dependent diabetic patients (IDDM) were asked to show a source of sugar and diabetes identification (ID). An attitude scale, developed and psychometrically evaluated with intent to examine ‘general attitude to diabetes’, was used to study attitudes. Fifty‐eight per cent of the IDDM patient sample carried both sugar and ID. The mean HbA1c of these patients (8.4%) was 2% lower (p<0.01) compared with patients carrying either ID only (24% of sample: mean HbA1c 10.4%), sugar only (6% of sample: mean HbA1c 10.3%) or neither item (12% of sample: mean HbA1c 10.7%). The general attitude score in these patients was significantly higher if sugar was carried (p<0.02) but there was no relationship with HbA1c (p>0.1). A seven‐item subcluster representing attitudes to diabetic management was more strongly related to sugar carriage (p<0.001) and was inversely correlated with HbA1c (r = 0.252: p< 0.02). These findings indicate that attitudes to diabetes management may influence specific behavioural elements (i.e. compliance with advice always to carry sugar and ID). However, there was also a significant trend to higher carriage rates for sugar with a higher frequency of perceived hypoglycaemia (p<0.05) but no relationship between perceived hypoglycaemia and HbA1c. Absence of sugar or ID appears to represent a useful indicator of poor diabetic control and may assist in the definition of relevant attitudinal differences.
Hyperglycaemia following Acute Myocardial Infarction: The Contribution of Undiagnosed Diabetes
Authors: Oswald G. A. , Yudkin J. S.
Published: July 2009

We studied 397 patients admitted to hospital with acute myocardial infarction (AMI) to validate an admission level of haemoglobin Alc (HbAlc) diagnostic for previously unknown diabetes mellitus by assessing glucose tolerance after 3 months. In 38% of survivors clearly abnormal HbAlc level (>7.8) was 100% sensitive and 99% specific for diabetes with fasting hyperglycaemia, although the sensitivity fell to 67% when three diabetic subjects without fasting hyperglycaemia were included. Admission hyperglycaemia (plasma glucose ≥11 mmol/l) was present in 20% of patients with AMI, of whom only one in five had levels of HbA1c indicating prior diabetes. Glycosylated haemoglobin is a more sensitive and specific test for diabetes in patients with AMI than admission hyperglycaemia. Undiagnosed diabetes was found in 4.3% of subjects with AMI who contributed 9.6% of hospital mortality.
Glycosylated Haemoglobin Measurement on Blood Samples Taken by Patients: An Additional Aid to Assessing Diabetic Control
Authors: Holman R. R. , Jelfs R. , Causier P. M. , Moore J. C. , Turner R. C.
Published: July 2009

200 patients attending a diabetic outpatient clinic were each asked to post to the hospital, prior to their three‐monthly routine clinic visit, a finger‐prick capillary blood sample for glycosylated haemoglobin assay (HbA1). Patients took their own blood into UNISTEP bottles, which automatically measure a 53 ***μl aliquot and mix it with 150 ***μl of a diluent suitable for transport to the laboratory. During 1 year 883 (84%) of 1046 bottles sent out were returned of which 776 (87%) were suitable for analysis. The availability of the result at the time of the patients' clinic visit aided assessment of diabetic control and was associated with a mean reduction of the HbA1 by 0.8% (p <0.001) over a twelve‐month period. This simple system facilitates remote monitoring of HbA1 levels, is suitable for both hospital and general practice use and may allow a reduction in the number of patient visits.
Proteinuria Prevalence in Insulin‐treated Patients: Prediction of Need for End‐Stage Renal Failure Treatment
Authors: Waugh N. R. , Jung R. T. , Newton R. W.
Published: July 2009

In the Dundee Diabetic clinic area (population circa 250 000), a population‐based survey of the prevalence of proteinuria in diabetic patients treated with insulin showed that 9.4% of such patients had persistent proteinuria. The percentage of males with proteinuria was 11.4%, against 7.2% of females. An additional 5.2% of patients had had proteinuria observed once, but did not meet the criteria for persistent proteinuria. No result was available in 10% of patients for a variety of reasons.

Not every patient with diabetes and persistent proteinuria will progress to end‐stage renal failure, but consideration of the group as a whole allows predictions based on published reports, to be made of the likely future incidence of renal failure, and hence future need for renal replacement services. We estimate that over the next decade two patients per 125 000 total population will develop renal failure each year. If survival is unchanged, there could be two or three times that number on treatment at any time.
Treating Hypertension in Non‐insulin‐Dependent Diabetes: A Comparison of Atenolol, Nifedipine, and Captopril Combined with Bendrofluazide
Authors: Corcoran J. S. , Perkins J. E. , Hoffbrand B. I. , Yudkin J. S.
Published: July 2009

Twenty‐five of thirty NIDDS who remained hypertensive (diastolic >95 mmHg supine) after 4 weeks on bendrofluazide 2.5 mg daily (B), completed a single‐blind, observer‐blind randomized crossover study, in which the additional use of atenolol (50 mg daily) (A), slow‐release nifedipine (20 mg twice daily) (N), and captopril (25 mg twice daily) (C) was compared. Patients took each drug for 8 weeks with dose doubling at 4 weeks if supine diastolic remained >90 mmHg. All three combinations were more effective than bendrofluazide alone (p<0.01). In nine patients studied 2 h after tablets at the end of each treatment period nifedipine was more effective than the other two drugs (B: 174/104 mmHg, A: 162/95 mmHg, −8%, N: 141/88 mmHg, −17%, C: 157/94 mmHg, − 10%, supine), whereas in 16 patients studied 15 h after their evening dose there was no significant difference. Fasting insulin and HbA1 levels were not significantly different between groups. No drug had a significant adverse effect on creatinine, glomerular filtration rate, overnight urinary albumin excretion or foot transcutaneous oxygen levels (43°C). All three drugs studied were effective without deleterious effects on renal function or peripheral blood flow.
The Natural History of Insulin‐Dependent Diabetes Mellitus in Denmark: 1. Long‐term survival with and without late diabetic complications
Authors: Borch‐Johnsen K. , Nissen H. , Henriksen E. , Kreiner S. , Salling N. , Deckert T. , Nerup J.
Published: July 2009

All 906 patients with insulin‐dependent diabetes mellitus (IDDM) diagnosed before the age of 31 years, prior to 1943, and admitted to the Steno Memorial Hospital were followed until death or until 1 January 1984. In an attempt to identify factors of prognostic importance, we compared patients dying within 35 years of the onset of diabetes with patients surviving for 40 years or more. Three hundred and seventy‐seven patients survived for 40 years or more; of these 224 were still alive and invited to a re‐examination, in which 184 participated.

After 40 years of diabetes, the most frequent complications were impaired vision (due to diabetic retinopathy) and persistent proteinuria. However, 53% had no major complications despite 40 years with IDDM. The 184 re‐examined patients (median age 60 years, median diabetes duration 47 years) were all genuine IDDM patients, as defined by stimulated C‐peptide levels. Proliferative retinopathy or visual impairment was found in 56% of the 184 patients, abnormal ECG or amputations in 26%, and elevated urinary albumin excretion rate (AER) ≥ 30 mg/24 h) in 45%. Twenty‐five per cent had none of these complications. Proliferative retinopathy was associated with elevated AER and raised systolic blood pressure, macroangiopathy with the use of antihypertensive drugs, and proteinuria with low age at diagnosis, large increase in systolic blood pressure, smoking, and insulin‐binding antibodies. Sex, age and diabetes duration were not associated with any of these three late diabetic complications.
A Long‐term Follow‐up of Dietary Advice in Maturity Onset Diabetes: The Experience of One Centre in the UK Prospective Study
Authors: Horrocks P. M. , Blackmore R. , Wright A. D.
Published: July 2009

The efficacy of simple dietary advice in 65 patients followed for 3 years at one centre participating in the UK prospective study of maturity onset diabetes was assessed. Whereas normal weight patients tended to keep to the prescribed calories, overweight patients tended to eat more. Total carbohydrate content was unchanged but there was a significant increase in unrefined carbohydrate and fibre.