bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Methods for Determination of Microalbuminuria in Diabetic Patients
Authors: Sawicki P.T. , Heinemann L. , Berger M.
Published: July 2009

Microalbuminuria is an early marker of prognostic significance in diabetic renal disease. The aim of the present study was to compare methods which do not require radioactive markers for estimating microalbuminuria (20–300 mg l−1) with a radioimmunoassay for albumin estimation. Albumin concentrations of 329 diabetic patients were measured using two laser turbidimetric methods for albuminuria and proteinuria, two semiquantitative tests (Albusure and Albustix), and a routine albumin radioimmunoassay. The four methods in the order laser immunoturbidimetric for albuminuria, laser turbidimetric for proteinuria, Albusure and Albustix gave the following results: sensitivity 0.97, 0.93, 0.97 and 0.81; specificity 0.92, 0.88, 0.94 and 0.55; positive predictive value for microalbuminuria 0.83, 0.75, 0.85 and 0.42; negative predictive value for microalbuminuria 0.99, 0.97, 0.99 and 0.88. We suggest that both laser turbidimetric methods are reliable and can replace methods with radioactive markers, the same being true for the Albusure test.
Efficacy and Acceptance of Two Intensified Conventional Insulin Therapy Regimens: a Long‐term Cross‐over Comparison
Authors: Houtzagers C.M.G.J. , Berntzen P.A. , Van der Stap H. , Van Maarschalkerweerd W.W.A. , Lanting P. , Boen‐Tan I. , Heine R.J. , Van der Veen E.A.
Published: July 2009

The efficacy and acceptability of multiple daily insulin injections (three preprandial injections of short‐acting insulin (NovoPen) plus once daily extended‐acting insulin) were compared with those of twice daily injections of short‐ and intermediate‐acting insulin. Sixteen Type 1 diabetic patients participated in a cross‐over study (6‐month treatment periods). Total areas under 24‐h plasma free insulin curves, assessed at the end of each study period, were not significantly different, but a greater area under this curve was found for the pen‐injector regimen from 1200 to 1600 h (150 ± 15 (SE) vs 106 ± 7 mU l−1 h, p < 0.01). Home blood glucose profiles showed significantly lower values with pen‐injector therapy after lunch (7.1 ± 0.6 vs 8.4 ± 0.4 mmol l−1, p = 0.05) and before and after dinner (6.4 ± 0.6 vs 8.8 ± 0.5 mmol l−1, p < 0.005, and 7.5 ± 0.7 vs 9.4 ± 1.1 mmol l−1, p < 0.05). Mean daily blood glucose concentration was also lower (7.1 ± 0.4 vs 8.2 ± 0.5 mmol l−1, p < 0.05). HbA1, fructosamine, hypoglycaemic reactions, and body weight were not significantly different. Thirteen patients decided to continue with pen‐injector therapy at the end of the study.
Abnormal Foot Pressures Alone May not Cause Ulceration
Authors: Masson E.A. , Hay E.M. , Stockley I. , Veves A. , Betts R.P. , Boulton A.J.M.
Published: July 2009

Both rheumatoid arthritis and diabetes have been associated with the development of abnormally high pressures under the feet, and ulceration has been considered to be a problem in both conditions. In order to examine further the relationship between high foot pressure, neurological abnormalities, and ulceration, we have studied two groups of patients: (a) 38 diabetic patients and (b) 37 patients with rheumatoid arthritis who had similar clinical abnormalities of the feet. Thirty‐two percent of diabetic patients had a history of plantar ulceration compared with none of the rheumatoid group (p < 0.01). However, the diabetic group had considerably more severe neuropathy (peroneal nerve motor conduction velocity 35.4 ± 4.8 m s−1 vs 44.4 ± 5.2 m s−1 (mean ± SD), p < 0.001; vibration perception threshold 33.5 ± 13.4 vs 16.9 ± 10.9, p < 0.001), with a similar frequency of elevated plantar pressures (51 % vs 61 %, NS). These data emphasize the importance of the loss of sensory awareness in the pathogenesis of diabetic foot ulceration, and suggest that high pressure alone is not a direct cause of ulceration.
Coronary Artery Disease, HDL Cholesterol, and Insulin‐gene Flanking Sequences
Authors: Johansen K. , Skotnicki A. , Smith R. , Dunn B. , Ziady G. , Skotnicki M.
Published: July 2009

The relationship between coronary artery disease, HDL cholesterol, and the hypervariable region flanking the human insulin gene was studied in Saudi Arabian non‐diabetic subjects (n = 68) and in patients with Type 2 diabetes (n = 35). A locus of insulin‐gene‐linked DNA polymorphism with three average size classes of alleles was found: a small class 1, a rare medium size class 2, and a large class 3 allele. In the total group of subjects (n = 103), those with the class 3 allele had a lower plasma HDL cholesterol concentration than those without the class 3 allele (0.93 ± 0.26 vs 1.12 ± 0.30 mmol l−1, 2p < 0.003). No difference in genotype and allelic frequency was found between patients with and without coronary artery disease in the combined group of subjects, with and without diabetes. Similarly the genotype distribution was not different between non‐diabetic subjects and patients with Type 2 diabetes in the combined group of subjects, both with and without coronary artery disease. In conclusion, the study did not confirm a previous study showing an association between the class 3 allele and atherosclerosis in a Caucasian population. However, the class 3 allele was associated with a low plasma HDL cholesterol concentration.
Hypoglycaemic Brittle Diabetes Successfully Managed by Social Worker Intervention
Authors: Gill G. , Robinson M. , Marrow J.
Published: July 2009

The case is presented of a 39‐year‐old Type 1 diabetic patient of 22 years duration with recurrent hypoglycaemic comas. He was of unusual personality and had bizarre ideas on self‐regulation of his diabetes, resulting in wide variations of insulin dosage. In one 12‐month period he had 88 separate admissions to an emergency department with severe hypoglycaemic coma requiring intravenous glucose administration. The cycle of admissions was eventually broken by the intervention of a social worker, who provided structured non‐medical support. The patient's diabetic misconceptions remained, but he appeared to gain sufficient insight to prevent recurrent hypoglycaemia.
Bilateral Renal Cortical Abscesses in a Young Woman with Type 1 Diabetes
Authors: Bevan J.S. , Griffiths G.J. , Williams J.D. , Gibby O.M.
Published: July 2009

Serious complications of urinary tract infection, such as papillary necrosis or perinephric abscess, occur more frequently in diabetic patients. However, severe bilateral renal parenchymal infection with multiple intrarenal abscesses is not well recognized. We describe an 18‐year‐old insulin‐dependent diabetic woman with such infection, in whom renal imaging showed progression to a major perinephric abscess, but only after 5 weeks of intensive antibiotic therapy. Complete recovery followed surgical drainage and no renal cortical scarring was present on computerized tomographic scan 18 months later.
A Comparison of Human Ultralente‐and Lente‐based Twice‐daily Injection Regimens
Authors: Tunbridge F.K.E. , Newens A. , Home P.D. , Davis S.N. , Alberti K.G.M.M. , Murphy M. , Burrin J.M. , Jensen I.
Published: July 2009

The problem of fasting hyperglycaemia remains unresolved on currently used twice‐daily injection regimens. Human ultralente insulin is of longer duration than human lente and differs from it only in the nature of the zinc‐insulin complex. In a 6‐month double‐blind crossover study these insulins were compared in 66 patients who were randomized to human ultralente or human lente insulin given together with human soluble insulin in a twice‐daily injection regimen. Patients were seen monthly and crossed over after 3 months treatment. Fasting blood glucose concentrations on the ultralente regimen were considerably lower than on the lente regimen, the difference being statistically significant (6.6 ± 0.5 vs 8.2 ± 0.5 mmol I−1, p < 0.05), but only present in those patients with fasting concentrations below the median. Glycosylated haemoglobin was identical on both regimens (9.3 ± 0.2 %). The evening ultralente dose was slightly but significantly lower than the evening lente dose (14.9 ± 0.8 vs 15.5 ± 0.8 U, p < 0.05) thus endorsing the lowering effect of ultralente on the fasting blood glucose concentration. However, the incidence of serious hypoglycaemic events was higher on the ultralente regimen (0.38 ± 0.10 vs 0.09 ± 0.04 events per patient‐month, p < 0.02), the majority of nocturnal events occurring between 0500 h and breakfast. We conclude that ultralente insulin can give an improved fasting blood glucose concentration but that in those patients with more marked fasting hyperglycaemia or with a nocturnal hypoglycaemia problem it offers no clinical advantage over human lente insulin in a twice‐daily injection regimen.
Wound Classification is More Important Than Site of Ulceration in the Outcome of Diabetic Foot Ulcers
Authors: Apelqvist Jan , Agardh C.‐D. , Castenfors J. , Larsson J. , Stenström A.
Published: July 2009

The importance of wound classification and site of ulceration was evaluated in 314 consecutive diabetic patients with foot ulcers. The ulcers were classified as superficial (through the full thickness of the dermis; n=150), deep (n=50), osteomyelitis and/or abscess (n=46), minor gangrene (n=39) or major gangrene (n=29). Wound healing was defined as intact skin for at least 6 months. In patients with superficial and deep ulcers, primary healing occurred in 88% and 78%, respectively, compared with 57% in those patient who developed an abscess and/or osteomyelitis. Only 2 out of 68 patients with gangrene healed (through mummification) without amputation. Patients with gangrene had lower ankle and toe blood pressure than patients with all other types of ulcers. There were only marginal differences in primary healing rate between different ulcer sites. The highest rate was seen in ulcers localized to the metatarsal heads (78%). Patients with multiple ulcers had the lowest primary healing rate (5%) compared with single ulcers at all sites. These differences were probably due to circulatory factors, since patients with multiple ulcers had lower distal perfusion pressures compared with all other groups.
Foot Bearing Pressure in Patients with Unilateral Diabetic Foot Ulcers
Authors: Smith L. , Plehwe W. , McGill M. , Genev N. , Yue D.K. , Turtle J.R.
Published: July 2009

Foot ulceration due to neuropathy is a serious cause of morbidity in diabetes. Ulceration usually occurs at the part of the foot subjected to excessive mechanical pressure. A more generalized increase in pressure under the feet has also been shown to be a feature of many patients with diabetic neuropathy. In this study the electrodynogram was used to measure the pressure at seven positions under each foot. The maximum vertical foot bearing pressure was found to be higher in 11 diabetic patients with previously healed unilateral foot ulcers (10.6±5.9 kg cm−2) than in 11 diabetic patients who did not have such a history (4.2±1.3 kg cm−2). However there was no difference in pressure between the foot with previous ulceration and the contralateral foot (9.7±6.8 kg cm−2, 11.6±7.9 kg cm−2). Vertical foot bearing pressure was decreased by an average of 18% by wearing shoes padded with a Professional Protective Technology insole and the decrease was greater in patients with higher foot pressure. These results showed that increased vertical foot pressure is an important, but not the only, factor in determining the occurrence of foot ulcer.
Symptomatic Awareness of Hypoglycaemia: Does it Change on Transfer from Animal to Human Insulin?
Authors: Hepburn D.A. , Eadington D.W. , Patrick A.W. , Colledge N.R. , Frier B.M.
Published: July 2009

A retrospective survey of symptomatic awareness of hypoglycaemia was performed in 189 randomly selected patients with insulin‐treated diabetes who had been transferred from highly purified animal insulins to human insulin in the preceding 24 months. Of the 189 patients 44 (23%) complained of chronic hypoglycaemic unawareness, unrelated to ambient blood glucose control, before change of insulin species. Only 12 of the remaining 145 patients reported a reduction in awareness of hypoglycaemia following transfer to human insulin (6% of the whole group), while 6 (3%) reported an increase in awareness following the transfer. The 12 patients reporting reduced awareness had a mean duration of diabetes of 24±10 years compared to a duration of 15±10 years in the patients with normal awareness. The mean glycosylated haemoglobin concentrations were similar in all of the groups of patients. Six patients had developed total loss of awareness of the onset of hypoglycaemia, with all but one patient having suffered multiple episodes of severe hypoglycaemia. This reduced hypoglycaemic awareness on human insulin therapy was not associated with any sigificant improvement in blood glucose control.
Elevated Neuropeptide Y Concentrations in the Central Hypothalamus of the Spontaneously Diabetic BB/E Wistar Rat
Authors: Williams G. , Lee Y.C. , Ghatei M.A. , Cardoso H.M. , Ball J.A. , Bone A.J. , Baird J.D. , Bloom S.R.
Published: July 2009

Insulin‐deficient diabetes causes hypothalamic and pituitary dysfunction. The possible role of hypothalamic regulatory peptides in mediating these disturbances was investigated in spontaneously diabetic BB/E Wistar rats. Concentrations of 10 regulatory peptides were measured in the central (nucleus‐rich) and lateral parts of the hypothalamus in 18 diabetic and 5 non‐diabetic BB/E rats. Diabetic rats were treated with either intensified or low‐dose insulin schedules to achieve moderate or severe hyperglycaemia (mean blood glucose concentrations, 8 and 20 mmol I−1 respectively). Neuropeptide Y concentration and content in the central hypothalamus were increased by 30–40% in both moderately and severely hyperglycaemic diabetic groups (p < 0.01). Lateral hypothalamic neuropeptide Y levels did not differ significantly between the groups. The only other peptide to show any significant difference between diabetic and control rats was calcitonin gene‐related peptide, whose central hypothalamic concentrations were significantly increased in the severely hyperglycaemic animals. Alterations of hypothalamic neuropeptide Y, which has potent experimental effects on hypothalamo‐pituitary function, may contribute to certain neuroendocrine disturbances in insulin‐deficient diabetes.
Increased Proximal Tubular Sodium Reabsorption in Hypertensive Patients with Type 2 Diabetes
Authors: Mbanya J.‐C. , Thomas T. H. , Taylor R. , Alberti K. G. M. M. , Wilkinson R.
Published: July 2009

Hyperinsulinaemia and sodium retention have been studied in 22 Type 2 diabetic patients (10 normotensive, 12 hypertensive) and 10 normal control subjects matched for age, sex, and body mass index. Exchangeable sodium was similar in the three groups. Plasma renin activity and plasma angiotensin II were lower in both groups of diabetic patients than in the normal control subjects (p<0.01). Plasma atrial natriuretic peptide was increased in the hypertensive patients (7.3 ± 1.1 vs normotensive 4.7 ± 1.1 pmol I−1 and control 4.0 ± 0.2 pmol I−1, p<0.01). Fractional lithium clearance, a measure of sodium clearance from the proximal tubule, was decreased (18.5 ± 1.4, p<0.01) and fractional excretion of sodium in the distal tubule was increased (6.66 ± 0.66, p<0.01) in untreated hypertensive diabetic patients compared with both normotensive diabetic patients (25.3 ± 1.6 and 3.96 ± 0.52 respectively) and normal control subjects (25.2 ± 2.9 and 3.31 ± 0.38, respectively). Fasting serum insulin was higher in hypertensive than in normotensive diabetic patients (18.5 ± 3.0 vs 10.7 ± 1.1 mU I−1, p<0.01) and higher in both groups than in normal control subjects (5.6 ± 0.1 mU I−1, both p<0.01). Creatinine clearance was higher in both groups of diabetic patients than in normal control subjects (p<0.05). Thus there appears to be increased proximal renal tubular sodium reabsorption in these hypertensive Type 2 diabetic patients, matched by a reduction in distal sodium reabsorption so that net sodium excretion was maintained. This was associated with fasting hyperinsulinaemia.
Autonomic Neuropathy and the Pathogenesis of Glaucoma in Diabetes Mellitus
Authors: Moore M.V. , Jeffcoate W.J. , Haworth S.
Published: July 2009

In order to determine whether ocular hypertension and glaucoma may be a complication of autonomic neuropathy in diabetes mellitus, 30 asymptomatic diabetic patient volunteers were studied. A correlation was sought between reduced anterior chamber depth which is thought to predispose to the development of glaucoma, and two markers of autonomic dysfunction, loss of sinus arrhythmia and reduced diameter of dark adapted pupils. A significant correlation was found between reduced chamber depth and reduced sinus arrhythmia (r = 0.36, p = 0.025) and between chamber depth and pupil diameter (r = 0.45, p = 0.006). As expected, there was also a significant correlation between sinus arrhythmia and pupil diameter (r = 0.68, p < 0.001). The correlation between pupil diameter and sinus arrhythmia, and between pupil diameter and chamber depth was preserved after the data were adjusted for age (r = 0.54, p < 0.001 and r = 0.35, p = 0.03, respectively), while that between sinus arrhythmia and chamber depth was lost (r = 0.23, NS). No association was found between intraocular pressure and either marker of autonomic dysfunction, but intraocular pressure was not abnormal (<22 mmHg) in any individual case. These data suggest that autonomic denervation of the eye in diabetes may be associated with alteration of anterior chamber depth.
Putative Risk Factors Associated with Retinopathy in Patients with Diabetes Diagnosed at or after 30 Years of Age
Authors: Agardh E. , Torffvit O. , Agardh C.‐D.
Published: July 2009

In a cross‐sectional study of diabetic patients diagnosed at or after 30 years, and with different stages of retinopathy, factors such as duration of diabetes, treatment mode, metabolic control, blood pressure, and clinical signs of nephropathy were examined. The different stages of retinopathy used were absence of retinopathy, simplex, and severe retinopathy. Patients with simplex and severe retinopathy were older than those without retinopathy (p < 0.001, and p < 0.01, respectively). They also had a longer duration of diabetes (p < 0.001), and were more often treated with insulin (p < 0.001) and in larger doses (p < 0.001). Their glycosylated haemoglobin levels were higher (p < 0.01). Their systolic blood pressure was higher (p < 0.01), but the diastolic blood pressure did not differ, and the number of patients treated for hypertension was similar in all groups. Albumin clearance was higher (p < 0.01 and p < 0.001), as were urinary albumin levels (p < 0.001). The only variables that distinguished patients with simplex from those with severe retinopathy were albumin clearance (p < 0.01) and urinary albumin levels (p < 0.05).
Continuous Subcutaneous Insulin Infusion (CSII) Versus Conventional Injection Therapy in Newly Diagnosed Diabetic Children: Two‐year Follow‐up of a Randomized, Prospective Trial
Authors: de Beaufort C.E. , Houtzagers C.M.G.J. , Bruining G.J. , Aarsen R.S.R. , de Visser J.J. , den Boer N.C. , Grose W.F.A. , van Strik R.
Published: July 2009

The effect of continuous subcutaneous insulin infusion (CSII), begun at diagnosis, on blood glucose control and endogenous insulin production was studied in a group of consecutively referred newly diagnosed diabetic children. In a random order, 15 children started CSII (age 9.5 ± 4.2 (±SD) years) and 15 conventional injection therapy (age 7.0 ± 3.6 years). For 2 years HbA1, and urinary C‐peptide were measured monthly, C‐peptide responses to glucagon 6‐monthly, and insulin antibodies every 3 months. None of the patients requested change of therapy during the study period, but at 28 months 1 adolescent girl changed to injection therapy from CSII. Severe hypoglycaemia was observed once in each group, but ketoacidosis only once, in the injection therapy group. From 2 months after diagnosis onwards the CSII group had significantly lower HbA1, levels. Urinary and plasma C‐peptide levels did not differ between the two groups and similar insulin doses were used throughout the study. At the end of the 2 years of therapy, the CSII group had significantly lower insulin antibody levels. The observations suggest that CSII is well accepted in newly diagnosed children and improves metabolic control, but does not prolong endogenous insulin production.
Triphasic Changes in Selectivity with Increasing Proteinuria in Type 1 and Type 2 Diabetes
Authors: Jerums G. , Allen T.J. , Cooper M.E.
Published: July 2009

Two indices of the selectivity of proteinuria, the immunoglobulin G (IgG)/albumin and the IgG/transferrin clearance ratios, were studied cross‐sectionally and serially over 7 years in a cohort of 52 Type 1 and 60 Type 2 diabetic patients without established diabetic nephropathy. In Type 1 and Type 2 diabetic patients with albuminuria <30 μg min−1, both protein clearance ratios were significantly higher than in 27 control subjects. As albuminuria increased, there was a decrease in both protein clearance ratios. However, at albumin clearances above 90 nl s−1 equivalent to albumin excretion rates of >250 μg min−1, a positive correlation was found in Type 2 diabetic patients between protein clearance ratios and albuminuria. In individual Type 1 and Type 2 diabetic patients with progressively increasing proteinuria, serial measurements of selectivity showed a decline in both protein clearance ratios with the onset of microalbuminuria. Episodes of transient microalbuminuria were also associated with a fall in the IgG/albumin clearance ratio. The results suggest that the selectivity of proteinuria undergoes a triphasic change with the development of diabetic nephropathy. In the first phase, proteinuria is non‐selective with IgG clearance equal to or exceeding transferrin or albumin clearance. As microalbuminuria develops, there is a progressive increase in selectivity reflecting the preferential excretion of transferrin and albumin compared with IgG. In later stages of nephropathy, as shown in Type 2 diabetic patients with macroalbuminuria, there is a return to non‐selective proteinuria.
Reduced Urinary Excretion of Epidermal Growth Factor in Incipient and Overt Diabetic Nephropathy
Authors: Mathiesen E. R. , Nexø E. , Hommel E. , Parving H.‐H.
Published: July 2009

To study the relationship between glomerular and tubular function we investigated glomerular filtration rate (GFR), urinary albumin excretion, and urinary excretion of epidermal growth factor (EGF, a mitogenic peptide synthesized in the renal tubular cells) in normal subjects (group I, n = 7) and in Type 1 (insulin‐dependent) diabetic patients with normoalbuminuria (group II, n = 11); with incipient nephropathy (microalbuminuria) (group III, n = 9); with nephropathy and normal GFR (group IV, n = 12); and with reduced GFR (group V, n = 8). EGF (nmol 24 h‐1) decreased with progressive glomerular involvement, from 7.9 (4.1–10.5) (median and range) in group I, to 6.7 (1.3–9.2) in group II, 5.0 (3.6–7.4) in group III, 4.1 (2.5–9.5) in group IV, and 1.1 (0.1–2.5) in group V. The urinary excretion of EGF was significantly reduced in patients with elevated UAE (group III, IV, and V) compared with normal control subjects (p < 0.05). A significant correlation between urinary excretion of EGF and GFR (r = 0.71, p < 0.001) and an inverse correlation between the urinary excretion of EGF and albumin (r = ‐0.35, p < 0.05) was demonstrated in the Type 1 diabetic patients with GFR>90 ml min‐1. Our study demonstrates that urinary excretion of epidermal growth factor diminishes with increasing nephron impairment, and that renal tubular function as judged by the excretion of EGF is reduced early in the development of diabetic kidney disease.
Split‐skin Grafting in the Management of Extensive Neuropathic Ulceration
Authors: Masson E. A. , Cooper M. A. C. , Boulton A. J. M.
Published: July 2009

Neuropathic foot ulceration can lead to long periods of in‐patient treatment, and healing time is related to the size of the skin defect. We report a case where most of the skin was lost from the plantar surface of the foot, and healing was dramatically assisted by the application of split‐skin grafts, a technique seldom considered for the treatment of diabetic foot lesions.
QT Interval Length and Diabetic Autonomic Neuropathy
Authors: Ewing D.J. , Neilson J.M.M.
Published: July 2009

QT interval length was measured in ECG recordings from three groups of age‐matched male subjects: 36 normal subjects, 41 diabetic patients without (DAN‐ve), and 34 with (DAN+ve) autonomic neuropathy. ECG samples were selected from previously recorded 24‐h ECGs on the basis of a clearly defined T wave and a steady RR interval over 2 min of around 750 ms (80 beats min−1). There were no significant differences in RR interval between the groups. The two diabetic groups had slightly longer QT measurements (normal 365 ± 14 (±SD) ms, DAN‐ve 373 ± 18 ms, DAN+ve 375 ± 23 ms, p = 0.05), and corrected QT (QTc) values (normal 423 ± 15 ms, DAN‐ve 430 ± 20 ms, DAN+ve 435 ± 24 ms, p = 0.05). Ten diabetic patients fell above our defined upper limit of normal for QTc (>mean + 2SD). There was a significant correlation in the DAN‐ve group between the QT indices and 24‐h RR counts (QT r = −0.38, p < 0.01; QTc r = −0.40, p < 0.01). We conclude that there are some small alterations in QT interval length in the steady state in diabetic autonomic neuropathy. The changes appear to be due to autonomic impairment, rather than diabetes per se.
Free Radical Activity in Type 2 Diabetes
Authors: Collier A. , Small M. , Wilson R. , Bradley H. , Thomson J.A.
Published: July 2009

Free radical activity has been implicated in the development of diabetic vascular complications in Type 1 diabetes. The aim of the present study was to investigate the levels of free radical scavengers, particularly erythrocyte superoxide dismutase, plasma and erythrocyte lysate thiol, and caeruloplasmin in 22 Type 2 diabetic patients clinically free of complications, and 15 comparable non‐diabetic control subjects. The concentration (median (range)) of both superoxide dismutase (23 (10–39) vs 45 (25–75) μmol I−1; p < 0.001) and plasma thiol (374 (172–523) vs 460 (386–595) μmol I−1; p < 0.01) were reduced in the diabetic group. There were no significant differences in the concentration of erythrocyte lysate thiol (199 (114–520) vs 188 (114–328) μmol I−1) or plasma caeruloplasmin (18 (9–31) vs 24 (6–50) μmol I−1) between the groups. This reduction in superoxide dismutase and the imbalance in the redox status of the plasma and lysate thiol demonstrated is consistent with an increase in free radical activity in Type 2 diabetes.
The Problem of Autonomic Neuropathy in Diabetic Pregnancy
Authors: Macleod A.F. , Smith S.A. , Sönksen P.H. , Lowy C.
Published: July 2009

The hazards of pregnancy for both the mother and the fetus in diabetic women with severe retinopathy and nephropathy are well reported. We wish to highlight a poorly recognized problem in the obstetric management of the diabetic mother, that of pregnancy in a patient with autonomic neuropathy. Two such cases are reported where the presence of autonomic neuropathy severely jeopardized the health of the mother, with the loss of the fetus in one, due to occurrence of severe and intractable vomiting. The presence of moderate to severe symptomatic diabetic autonomic neuropathy, particularly with evidence of gastroparesis, may be a relative contraindication to pregnancy.
BOOK REVIEW
Authors: Young G.
Published: July 2009

Book reviewed in this article:

Lipids and Heart Disease: A Practical Approach by M. Ball and J. Mann
QT Prolongation on the Electrocardiogram in Diabetic Autonomic Neuropathy
Authors: Chambers J. B. , Sampson M. J. , Sprigings D. C. , Jackson G.
Published: July 2009

Patients with Type 1 diabetes and autonomic neuropathy have an increased risk of sudden death for which the mechanism remains obscure. Prolongation of the QT interval on the electrocardiogram may occur with sympathetic dysfunction and is also associated with ventricular arrhythmia and sudden death. We have therefore measured the QT interval in patients with Type 1 diabetes with normal, borderline, and definitely abnormal autonomic function tests and in non‐diabetic control subjects. The maximum QT interval was measured on 12‐lead electrocardiograms recorded at rest and then plotted against the RR interval. The QT interval was above the upper 95% limit for the non‐diabetic control subjects in 5 diabetic patients with abnormal autonomic function tests (33%), but in no cases with normal or borderline tests. Multivariate analysis confirmed that autonomic score contributed significantly (p < 0.025) to the variance in QT interval. The raw Valsalva ratio alone also contributed significantly to the variance in QT interval (p = 0.025). Heart rate variability, heart rate response to standing, age, sex, and the presence of symptoms of autonomic neuropathy did not contribute significantly.
Rising Incidence of Type 1 Diabetes in Hungarian Children (1978–1987)
Authors: Soltész G. , Madácsy L. , Békefi D. , Dankó I. ,   Hungarian Childhood Diabetes Epidemiology Group
Published: July 2009

A retrospective epidemiological study using primary data sources and external validation was conducted to assess the incidence of childhood (0 to 14 years) Type 1 diabetes in Hungary (excluding the Budapest region) over a 10‐year period. Hospital records and regional diabetes centres' registries served as primary data sources, and data were validated by using the records of summer camps for diabetic children. The degree of ascertainment was 96.2%. Age‐specific incidence rates increased until puberty with peak incidence in girls at 10 yr, and in boys at 13 yr. There was a significant seasonal variation of onset with peaks in autumn and winter. The incidence was slightly lower amongst boys than amongst girls. A statistically significant increase in incidence was evident in the last decade, from 3.8 per 100 000 in 1978 to 8.2 per 100 000 in 1987.
Activated CD4+ and CD8+ T‐lymphocytes in Newly Diagnosed Type 1 Diabetes: a Prospective Study
Authors: Buschard K. , Damsbo P. , Röpke C.
Published: July 2009

Peripheral lymphocytes from 13 Type 1 diabetic patients (age 28 ± 11 (±SD) years) were studied at diagnosis, and 1 month and 7 months later. The lymphocytes were labelled with phycoerythrin‐conjugated anti‐HLA‐DR antibody and/or fluorescein‐conjugated OKT4 or OKT8 antibody, and then studied using a double channel flow‐cytometer. The overall percentage of activated T‐lymphocytes (CD4+ + CD8+ cells) was (mean ± SE) 3.1 ± 0.5% at diagnosis, 2.1 ± 0.3% at 1 month and 2.2 ± 0.5% at 7 months test. The percentages at diagnosis and 1 month were higher than in 12 healthy control subjects (1.0 ± 0.2%, p < 0.001 and p < 0.01, respectively). Among the CD4+ cells the percentage of activated cells fell from diagnosis (2.8 ± 0.7%), to 1 month (1.5 ± 0.3%, p < 0.05), and 7 months (1.5 ± 0.4%, p < 0.05), whereas among the CD8+ cells they remained unchanged (3.3 ± 0.6, 2.5 ± 0.5 and 3.1 ± 0.6%). The percentage of activated CD4+ cells at diagnosis, and of CD8+ cells at all times, were higher (p < 0.02) than in control subjects (CD4+, 0.8 ± 0.2%; CD8+, 1.2 ± 0.2%). In conclusion, the activated T‐lymphocytes present in Type 1 diabetic patients at diagnosis are equally increased among CD4+ and CD8+ cells, but after 7 months the increase is predominantly in CD8+ cells.
Combination of Insulin with Glipizide Increases Peripheral Glucose Disposal in Secondary Failure Type 2 Diabetic Patients
Authors: Simpson H.C.R. , Sturley R. , Stirling C.A. , Reckless J.P.D.
Published: July 2009

Twenty Type 2 diabetic patients, recently converted to insulin because of inadequate control on oral hypoglycaemic agents, were studied. Endogenous insulin reserve was measured by glucagon stimulation, and insulin‐mediated peripheral glucose disposal by a hyperglycaemic (11 mmol I−1) clamp, measurements being repeated after 8 weeks of glipizide or placebo therapy in addition to the patients' usual insulin. The study was randomized and double blind. Fasting and stimulated C‐peptide levels did not change on glipizide or placebo. Insulin‐mediated glucose disposal rose from 2.5 (1.5–8.0) (median (range)) to 4.2 (2.3–8.4) mg kg−1 min−1 in the glipizide group (n = 9, p < 0.01), but did not change in the placebo group. Glycosylated haemoglobin did not change in either group, but median fasting plasma glucose fell from 10.6 (6.1–15.1) to 9.0 (6.4–11.2) mmol I−1 in the glipizide group (p<0.02). Fasting insulin rose on glipizide from 10.1 (4.0–23.2) to 13.0 (6.4–33.8) mU I−1 (p < 0.02). Insulin dosage fell in the glipizide group from 36 to 26 U day−1, as 4 patients experienced hypoglycaemic symptoms. HDL‐Cholesterol fell in all patients on glipizide, from 0.94 (0.79‐2.13) to 0.79 (0.62‐1.95) mmol I−1 (p < 0.01). Combination of insulin with the sulphonylurea glipizide in secondary failure Type 2 diabetic patients leads to increased insulin‐mediated peripheral glucose disposal. Glipizide may have an adverse effect on HDL‐cholesterol, which is unrelated to change in diabetic control.
Non‐mydriatic Retinal Photography as a Screening Service for General Practitioners
Authors: Rogers D. , Bitner‐Glindzicz M. , Harris C. , Yudkin J.S.
Published: July 2009

Non‐mydriatic retinal photography was offered as a screening service to 37 general practitioners providing diabetes care in their practices. Of 84 patients photographed, 22 had appearances of diabetic retinopathy and these were compared with 25 of the remainder without retinopathy. In only seven of 11 patients with maculopathy or proliferative retinopathy had this been detected by their GP and, likewise, only six of 11 cases of probable background retinopathy had been detected. The mean annual examination rate in general practice was 33 (95% CI 18–47)%. Of the 18 cases in whom action in response to recommendations for follow‐up or referral could be ascertained, 15 (83%) had had the recommendations implemented. Thus, despite the potential risks of false‐negative screening using non‐mydriatic retinal photography, the technique may improve the comprehensiveness of screening in patients under the care of their GPs.
The Organization of Services for Children with Diabetes in the United Kingdom: Report of the British Paediatric Association Working Party
Authors:   British Paediatric Association Working Party
Published: July 2009

A British Paediatric Association Working Party was set up in 1987 to examine the organization of services for children with diabetes in the United Kingdom. A questionnaire survey identified 360 consultant paediatricians providing care for children with diabetes in 205 Districts or Health Boards. Sixty‐three per cent (227) of paediatricians saw children in a designated paediatric diabetic clinic, 61% (220) reported that a diabetes nurse specialist regularly attended the clinic, and 70% (251) that a dietitian did so. Haemoglobin A1 or other glycosylated proteins were regularly measured by 91% (326) of paediatricians, 76% (274) regularly tested for urinary protein, and 79% (285) and 86% (310) checked blood pressure and eyes, respectively. However, 27% (55) of the Districts or Health Boards in the survey had no designated paediatric diabetic clinic. When the data were analysed by assigning paediatricians to categories according to their degree of specialization in diabetes only 33% (118) paediatricians could be described as having a specialist interest in diabetes. There were significant differences in the services provided by the specialist paediatricians when compared with the non‐specialists, particularly with respect to the professional staff regularly seeing children in clinics and services to the adolescents. The Working Party recommends that services for children with diabetes may be improved by encouraging at least one paediatrician in each District to develop a special expertise in diabetes. Designated children's diabetic clinics with appropriate supporting staff and services should be available in all Districts.
Isoform Patterns of Apolipoprotein E in Diabetes Mellitus
Authors: Black S.C. , Hewett S. , Kotubi Y. , Brunt R.V. , Reckless J.P.D.
Published: July 2009

Apolipoproteins in delipidated VLDL preparations from normal, diabetic, and non‐diabetic hyperlipidaemic subjects were analysed by SDS‐polyacrylamide gel electrophoresis, and by isoelectric focusing. On electrophoresis, diabetic VLDL contained more apolipoprotein E (17.3 ± 7.3 (± SD)%, n = 54) than did VLDL from hyperlipidaemic (13.4 ± 4.2%, n = 52; p < 0.005) or normal (12.4 ± 2.6%, n = 29; p < 0.001) subjects. Apolipoprotein E excess was also seen when subgroups were characterized by apolipoprotein E phenotype. In diabetic patients of E3/E3 phenotype, apolipoprotein E was 16.4 ± 6.0% (n = 25), compared with 12.9 ± 2.5% in control subjects (n = 14; p = 0.008). Acidic isoforms were more common in 44 diabetic patients with E3/E3 phenotype; E3, E2, E1, and E1′ as percentage of total E apolipoprotein were 58.3 ± 7.6, 24.5 ± 4.4, 13.7 ± 4.5, and 3.8 ± 4.3% respectively, compared with 63.5 ± 10.4 (p = 0.034), 19.1 ± 5.3 (p < 0.001), 13.7 ± 6.5 (NS), and 3.7 ± 2.1% (NS) in 21 normal subjects. In 31 diabetic patients, of apolipoprotein E3/E3 phenotype, E3, E2, E1 and E1′ were 60.2 ± 7.3, 23.4 ± 9.4, 11.1 ± 4.1, and 5.4 ± 3.7%, respectively, compared with 68.0 ± 7.1 (p < 0.001), 21.9 ± 6.4 (NS), 6.3 ± 3.9 (p < 0.001), and 3.7 ± 2.5 (p < 0.05)% in 32 hyperlipidaemic patients. Diabetic patients of E3/E2 phenotype showed less apolipoprotein E3 than normal or hyperlipidaemic subjects, with a similar trend for apolipoprotein E4 in those of E4/E3 phenotype. Increases in minor apolipoprotein E isoforms imply more post‐translational protein modification in people with diabetes.
The Diabetes Physician and an Assessment and Treatment Programme for Male Erectile Impotence
Authors: Alexander W. D.
Published: July 2009

The feasibility has been investigated of a physician in a district general hospital implementing an assessment and treatment service for male erectile impotence. Over an 8‐month period a questionnaire was given to 200 men attending a diabetes review clinic. There were 50 replies declaring a problem of impotence, 34 of whom expressed interest in discussing treatment. These men and 17 others who spontaneously mentioned an impotence problem were further assessed with a view to treatment. After a full assessment and discussion the following treatments were agreed and successfully implemented: no treatment 30 (59%), self‐injection of papaverine 12 (24%), urology referral 4 (8%), psychosexual clinic referral 2 (4%), vacuum devices 2 (4%), adjustment of drug therapy 1 (2%). Only 18% of questionnaire respondents ultimately opted for active treatment compared with 88% of the spontaneous complainants. A successful impotence assessment and treatment service, including self‐injection of vasoactive drugs, can be provided by a physician as part of the diabetes care service. Active treatment is gratefully accepted. The numbers involved are manageable if resources are concentrated on those spontaneously mentioning the problem. Our experience suggested self‐injection of vasoactive drugs to be the most successful treatment option.
Changing Sex Ratio in Diabetic Ketoacidosis
Authors: Wright A.D. , Hale P.J. , Singh B.M. , Kilvert J.A. , Nattrass M. , FitzGerald M.G.
Published: July 2009

An annual audit of diabetic ketoacidosis and hyperosmolar non‐ketotic state was made in one hospital from 1971 to 1988. There were 846 episodes of ketoacidosis and 126 episodes of hyperosmolar state. A relative fall occurred in the number of episodes of ketoacidosis compared with hyperosmolar state over this time (p < 0.05), and there was a change of female:male ratio for episodes of ketoacidosis occurring in established diabetes from 2.79 to 1.59 (p < 0.01). In contrast the female:male ratio remained unchanged (mean 1.16) for episodes of hyperosmolar state and remained less than 1.0 for all episodes of ketoacidosis in previously undiagnosed diabetes mellitus. Among patients who suffered recurrent ketoacidosis there was a reduction in the number of episodes occurring in female patients and an increase in the number of episodes occurring in male patients in each successive 6‐year period with consequent change in female:male ratio for this subgroup from 7.33 to 4.75 to 1.12 (p < 0.001).
Diabetes Education in the USSR: How to Begin?
Authors: Starostina E.G. , Antsiferov M.B.
Published: July 2009

To determine patients' attitudes towards diabetes education in the Soviet Union, a questionnaire was distributed throughout the country. From 10 000 completed forms, returned from all regions of the USSR, 2000 were analysed in detail. Responders represented all age and social groups, but patients with shorter duration of diabetes, and women, responded more readily. More than 41 % of patients were unaware of the type of diabetes they had, the actual proportions of Type 1 and Type 2 diabetes among respondents being 31 and 63 %. Rates of chronic complications derived from patients' answers suggest a high rate of underestimation by local physicians. Only 17 % of Type 1 and 8 % of Type 2 diabetic patients believed that they knew enough about diabetes, and 99.9 % of all respondents wanted to learn more about their disease. Independently of the type of diabetes and educational level, patients would accept the information on diabetes from periodicals (63–68 %), television (48–63 %), booklets for patients (29–31 %), as well as attending diabetes courses or classes (30–38 %). They expressed preference for teaching conducted by physicians (74–85 %) rather than nurses (1–4 %). The main areas of interest for Type 1 diabetic patients were technical devices, (artificial pancreas and insulin pumps (85 %)) and late diabetic complications (78 %), and for patients with Type 2 diabetes late complications (84 %) and diet (72 %). Some respondents (20–25 %) expected the use of herbs and other ‘non‐traditional’ methods to be effective in treatment and curing of diabetes. The least requested topics were acute complications (18–34 %) and metabolic self‐monitoring (0.025 %). The results obtained should be taken into consideration while establishing an approach to diabetes education in the USSR, and need more accurate definition for each smaller population before starting with teaching programmes.
The Prevalence of Diabetes in Elderly People
Authors: Croxson S.C.M. , Burden A.C. , Bodington M. , Botha J.L.
Published: July 2009

The prevalence of diabetes mellitus was investigated in a sample of people aged 65 to 85 years, using a modified oral glucose tolerance test and 1985 WHO criteria. Of the sample of 861, 52 had previously been diagnosed diabetic; 583 consented to be tested and 19 were diabetic. The prevalence of previously diagnosed diabetes was 6.0 (95% CI 4.3 to 8.1)%, and the prevalence of previously undiagnosed diabetes was 3.3 (95% CI 2.0 to 5.0)%. The high prevalence of previously diagnosed diabetes might be due to the longstanding community diabetes care in the area studied
Hypoglycaemia Unawareness in Type 1 Diabetes: A Lower Plasma Glucose is Required to Stimulate Sympathoadrenal Activation
Authors: Hepburn D. A. , Patrick A. W. , Brash H. M. , Thomson I. , Frier B. M.
Published: July 2009

To investigate the relationship between awareness of symptoms and the autonomic reaction of hypoglycaemia, acute hypoglycaemia was induced with intravenous insulin (2.5 mU kg−1 min−1) in diabetic and non‐diabetic subjects, all of whom had normal cardiovascular autonomic function tests. Three groups were studied: (1) nine patients with Type 1 diabetes with loss of awareness of hypoglycaemia; (2) eight patients who had normal awareness of hypoglycaemia, matched for duration of diabetes and blood glucose control; (3) eleven non‐diabetic volunteers. The onset of the acute autonomic reaction was identified objectively by the sudden and rapid responses of heart rate and sweating. Cognitive function and hypoglycaemia symptom scores were estimated serially. Acute autonomic activation was observed to occur in all subjects in response to hypoglycaemia. In the ‘unaware’ diabetic patients, onset of the reaction occurred at a significantly lower plasma glucose (1.0 ± 0.1 mmol l−1) than in the ‘aware’ diabetic patients (1.6 ± 0.2 mmol l−1) (p < 0.05) or in the non‐diabetic control group (1.4 ± 0.1 mmol l−1) (p < 0.05). Obvious neuroglycopenia was observed only in the ‘unaware’ diabetic group and developed when plasma glucose had declined to approximately 1.4 ± 0.1 mmol l−1, and thus preceded the reaction (p < 0.02 vs the autonomic threshold). The maximal rise in plasma adrenaline was of similar magnitude in all three groups but a lower plasma glucose was required to stimulate this hormonal response in the ‘unaware’ patients, in whom the plasma adrenaline concentration was lower at the time of the reaction. Thus, the plasma glucose at which activation of the autonomic reaction was observed was lower in the diabetic patients with unawareness of hypoglycaemia.
Contrasting Fibrinolytic Responses in Type 1 (Insulin‐dependent) and Type 2 (Non‐insulin‐dependent) Diabetes
Authors: Walmsley D. , Hampton K. K. , Grant P. J.
Published: July 2009

To study fibrinolysis in relation to microvascular diabetic complications, 20 control subjects were compared with 50 Type 1 (insulin‐dependent) diabetic patients of similar age, 20 with no complications, 17 with laser‐treated retinopathy, and 13 with neuropathy and retinopathy. None were smokers, hypertensive or had macrovascular disease. Pre‐ and post‐venous occlusion blood samples for tests of fibrinolysis were taken. Median (interquartile range) basal tissue plasminogen activator (t‐PA) activity was lower in control subjects (100(<100–100) IU l−1) than diabetic patients (uncomplicated 145 (100–280) IU l−1, p = 0.015; retinopathy 180 (100–228) IU l−1, p = 0.037; neuropathy 210 (125–310) IU l−1, p = 0.004, respectively). Basal t‐PA inhibition (PAI‐1 activity) was higher in control subjects (5.9 (4.5–9.5) kIU l−1) than diabetic patients (uncomplicated 4.0 (3.3–5.0) kIU l−1, p = 0.001; retinopathy 4.5 (3.1–6.3) kIU l−1, p = 0.058; neuropathy 4.0 (3.0–5.4) kIU l−1, p = 0.015, respectively). Post‐venous occlusion t‐PA antigen was higher in control subjects (10.2 (7.3–15.1) μg l−1) than neuropathic patients (5.5 (4.9–7.3) μg l−1, p = 0.004). Other tests showed a consistent, but non‐significant, trend towards increased basal fibrinolysis in the Type 1 diabetic patients. The results indicate that Type 1 diabetic patients have enhanced basal fibrinolysis. The diminished response to venous occlusion in neuropathic patients is consistent with an endothelial cell defect. These findings are in marked contrast to those in 20 uncomplicated Type 2 diabetic patients who had diminished basal and post‐venous occlusion fibrinolytic activity with high basal t‐PA (13.4 (9.8–16.8) μg l−1) and PAI‐1 (26.5 (12.4–39.6) μg l−1) antigen. The differing fibrinolytic responses may contribute to the heterogeneous nature of vascular disease in diabetes.
A System for Peri‐operative Blood Glucose Control in Diabetes Mellitus
Authors: Watson B. G. , Williamson M. , Pay D. A.
Published: July 2009

A pocket computer has been programmed to control the rate of administration of insulin given to diabetic patients having open heart surgery. Twelve diabetic patients were studied. Five had coronary artery bypass grafting, and seven had heart valve surgery. During operation 122 out of 162 (75%), and post‐operatively 291 out of 360 (81%) blood glucose concentrations were between 4.0 and 8.0 mmol I−1. Five hundred and fifteen values out of 552 (99%) were below 12.0 mmol I−1. There was no hypoglycaemia. The lowest measured blood glucose concentration was 3.7 mmol I−1. The computer is readily available, easy to use by inexperienced personnel, and cheap.