bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening for Microalbuminuria: Which Measurement?
Authors: Marshall S.M.
Published: July 2009

It now seems worth while to identify Type 1 diabetic patients with microalbuminuria, as improved blood glucose control and reduction of arterial blood pressure will slow if not prevent the progression to persistent proteinuria. Measurement of albumin excretion rate (AER) in a timed urine sample remains the gold standard for the definition of microalbuminuria, but is not a practical screening procedure. Thus attempts have been made to relate the albumin concentration or albumin:creatinine ratio in random or first morning urine samples to AER. There is a weak correlation of albumin concentration (r = 0.32 to 0.68) and albumin:creatinine ratio (r = 0.43 to 0.54) in a random urine sample with AER, and low sensitivity and specificity of a variety of different albumin concentrations and albumin:creatinine ratios to predict microalbuminuria. The correlation of albumin concentration (r = 0.86 to 0.90) and albumin:creatinine ratio (r = 0.74 to 0.91) in an early morning urine sample with AER is stronger. Measurement of albumin:creatinine ratio in an early morning urine sample appears to be the most reliable method of screening for microalbuminuria, with sensitivity of 88 to 100% and specificity 81 to 100% depending on the cut—off ratio chosen and the definition of microalbuminuria used. If the albumin:creatinine ratio in an early morning urine sample is ≤3.5 mg mmol−1, the patient can be classed as normoalbuminuric and re—screened annually. If the ratio is 10.0 mg mmol−1, confirmation of microalbuminuria should be sought in a timed urine collection and appropriate therapy begun. If the ratio is 3.6 to 9.9 mg mmol−1, there is a high risk of more rapid progression to definite microalbuminuria and the patient should be re‐screened more frequently.
Severe Hypoglycaemia During Treatment with Glipizide
Authors: Asplund K. , Wiholm B.–E. , Lundman B.
Published: July 2009

In the years 1980–87, 19 cases of severe hypoglycaemia during treatment of Type 2 diabetes with glipizide were reported to the Swedish Adverse Drug Reactions Advisory Committee. Patient age was 75 ± 9 years (mean ± SD) (significantly higher than in all patients on glipizide in Sweden), and the duration of glipizide treatment ranged from 1 day to 4 years. Eleven patients presented with coma, three with reduced consciousness and five with other symptoms. An uneventful early recovery occurred in 14 patients. The remaining five patients had prolonged or recurrent hypoglycaemia for up to 60 h. Two of the patients, both with complicating disorders, died. In a case‐control substudy, patients with glipizide‐associated hypoglycaemia were found to have renal impairment more often than age– and sex‐matched controls treated with glipizide (odds ratio 4.0). The median dose of glipizide (10 mg per day) was identical to that in controls. Other drugs, notably diuretics and benzodiazepines, were more commonly used by hypoglycaemic patients (median 5 vs 2 concomitant drugs, p < 0.001). We conclude that the use of glipizide is associated with a risk of developing severe hypoglycaemia with a clinical course that is not always benign.
Relation of Lipid Peroxides to Macrovascular Disease in Type 2 Diabetes
Authors: Velázquez E. , Winocour P.H. , Kesteven P. , Albert K.G.M.M. , Laker M. F.
Published: July 2009

Lipid peroxides are thought to be formed by free radicals and may play an important role in the development of atheromatous vascular disease. We have investigated the relationship between lipids, lipoproteins, coagulation factors, and lipid peroxides (measured as thiobarbituric acid reacting species (TBARS)) in Type 2 diabetic patients with macrovascular disease. Eighteen diabetic and 20 non‐diabetic subjects with clinical evidence of ischaemic heart disease and/or peripheral vascular disease were investigated, together with 28 healthy subjects without evidence of vascular disease. TBARS concentrations in non‐diabetic (mean 5.0 (95% CI 4.5–5.7) μmol I−1) and diabetic groups (5.6 (5.1–6.0) μmol I−1) with macrovascular disease were not significantly different although values were higher in both groups of patients with vascular disease by comparison with control subjects (2.7 (2.4–3.1) (μmol I−1, p < 0.001). Significant univariate correlations between TBARS concentrations and measures of blood glucose control (fructosamine, blood glucose and HbA,) were found for all 66 subjects (r = 0.35–0.42, p < 0.01–p < 0.001), although no independent association between these parameters and TBARS was demonstrated in multiple regression analysis. In addition, TBARS levels were significantly correlated in univariate analysis with the apolipoprotein (apo) Al:apoB ratio (r = −0.56, p< 0.001), total cholesterol:high density lipoprotein cholesterol ratio (r = 0.52, p < 0.001), apoB (r = 0.51, p < 0.001), low density lipoprotein cholesterol (r = 0.40, p < 0.001), serum total triglyceride (r = 0.46, p < 0.001), apoAl (r = −0.35, p < 0.01) and serum total cholesterol (r = 0.39, p < 0.001). Multiple regression analysis of continuous variables showed that apoB (p < 0.001), age (p < 0.001), and apoAl (p = 0.008) were independently associated with serum TBARS although these associations disappeared if macrovascular disease was added to the regression equation as a categorical variable. Our data support previous studies which demonstrate increased serum concentrations of TBARS in subjects with macrovascular disease but suggest that levels are similarly elevated in diabetic and non‐diabetic subjects.
Quality of Life, Perceived Difficulties in Adherence to a Diabetes Regimen, and Blood Glucose Control
Authors: Hanestad Berit Rokne , Albrektsen G.
Published: July 2009

The first aim of the present study was to investigate if self‐assessed quality of life was associated with perceived difficulties in adherence to a regimen, and the second, if perceived difficulties in adherence were associated with poor blood glucose control. A self‐administered questionnaire was completed by 247 patients with Type 1 diabetes who consecutively attended a Norwegian diabetes clinic. Results from multiple linear regression analysis indicated that a higher level of quality of life was associated with greater perceived ease of adherence to the regimen. Adherence to control of smoking, increased physical exercise, and control of weight and diet were perceived as most difficult. Analysis of covariance showed that women who perceived difficulties in adherence to self‐care behaviour had on average less satisfactory blood glucose control than those reporting less difficulty in adherence.
Islet Cell Cytoplasmic Antibodies (ICA) in Diabetes and Disorders of Glucose Tolerance
Authors: Marner B. , Bille G. , Christy M. , Damsgaard E. M. , Garne S. , Heinze E. , Larsen S. , Lernmark Å , Mandrup‐Poulsen T. , Nerup J. , Schroll M.
Published: July 2009

Islet cell cytoplasmic antibodies were determined in 85 individuals 60 to 74 years old with fasting hyperglycaemia, in 65 patients with cystic fibrosis, in 113 patients with pancreatitis, in 21 patients with Turner's phenotype, and in 135 first‐degree relatives of patients with Type 1 (insulin‐dependent) diabetes. Islet cell antibodies were absent in all 60 to 74‐year‐old subjects with fasting hyperglycaemia detected by screening, and who did not require insulin treatment within 3 years. Islet cell antibodies were also absent in all patients with pancreatitis, cystic fibrosis, or Turner's phenotype. Islet cell antibodies were detected in 2 out of 135 (1.5 %) first‐degree relatives of new Type 1 diabetic patients, and in 1 out of 371 (0.3%) non‐diabetic control subjects. During 12 years of follow‐up 1 of the 2 first‐degree relatives with islet cell antibodies and the only positive control developed Type 1 diabetes. It is suggested that islet cell antibodies are primarily associated with Type 1 diabetes and not with other disorders of glucose tolerance.
A Six‐year Follow‐up of the Relationship Between N‐Acetyl‐β‐glucosaminidase and Albuminuria in Relation to Retinopathy
Authors: Škrha J. , Haas T. , Šperl M. , Stibor V. , Štolba P.
Published: July 2009

Fifty patients with Type 1 diabetes mellitus were observed over 6 years. Serum and urinary N‐acetyl‐β‐glucosaminidase (NAG) activity, and albuminuria were measured in groups of patients subdivided according to ophthalmological findings. Significantly higher mean serum NAG activity was found at the beginning of the study in patients who later developed diabetic retinopathy in comparison with those who did not (geometric mean (2SD range) 19.7 (12.4–31.2) vs 14.4 (9.5–22.7) U l‐1 p < 0.01). Urinary NAG activity was significantly higher in all groups of diabetic patients than in healthy control subjects (p < 0.05). A significant increase in albumin: creatinine ratio during the study was found in patients with newly developed diabetic retinopathy compared with patients who did not (at 6 years 1.33 (0.40–4.43) vs 0.75 (0.24–2.31) g mol‐1, p < 0.01). No differences in either biochemical variable were found between hypertensive and normotensive diabetic patients at the end of the study. The results suggest that both serum NAG activity and albuminuria may serve as early functional indicators of diabetic retinopathy.
Siblings of Children with Diabetes: Involvement, Understanding and Adaptation
Authors: Adams R. , Peveler R. C. , Stein A. , Dunger D. B.
Published: July 2009

The psychosocial adjustment of 30 siblings (aged 8–18 years) of children with diabetes mellitus was studied. Although most were younger than the diabetic child, 55% were closely involved in the dietary management and insulin treatment of the diabetes, yet many had only a limited understanding of the disease. Most were well‐adjusted. However, low levels of self‐esteem were apparent among some subjects, who did not feel free to question their parents about diabetes (30%), who identified themselves as the member of the family most likely to receive blame (33%), and who reported spending more time at home with their families than their peers (40%). Nine children (30%) worried about becoming ill themselves. None believed that having a child with diabetes in the family had impaired relationships in the home. Six siblings (20%) also described some positive effects of the illness, particularly enhanced family closeness.
The Relationship of Oxidative Stress to Thrombotic Tendency in Type 1 Diabetic Patients with Retinopathy
Authors: Jennings P. E. , McLaren M. , Scott N. A. , Saniabadi A. R. , Belch J. J. F.
Published: July 2009

Increased free radical activity may contribute to thrombosis via effects on platelet aggregation and the prostanoid balance. To investigate this further we studied 15 Type 1 diabetic patients with retinopathy, matched with uncomplicated Type 1 patients for age, duration of diabetes and HbA1, together with matched healthy non‐diabetic control subjects. The oxidative effects of free radicals as total diene conjugates and lipid peroxides were measured, together with redox status extracellularly as plasma albumin‐thiols and intracellularly as erythrocyte superoxide dismutase activity. Platelet count, aggregation of platelets in whole blood to collagen, thromboxane B2, and prostacyclin stimulating factor (PGI2SF) were also assessed. Free radicals measured as lipid peroxides were significantly higher (9.6 (8.1–11.6) μmol 1‐1 (median and interquartile range) in diabetic patients with retinopathy than in control subjects (8.1 (7.4–9.2) μmol l‐1; p < 0.05). There were also significant reductions in redox status both extracellularly as plasma albumin thiols (408 (383–473) vs 490 (456–517) μmol l‐1, p < 0.001) and intracellularly as erythrocyte superoxide dismutase activity (34 (27–41) vs 44 (36–51) g l‐1, p < 0.05) between patients with retinopathy and control subjects. Platelet counts were increased in diabetic patients with retinopathy (p < 0.05), as was collagen‐induced platelet aggregation (p < 0.01). Prostacyclin stimulating factor was reduced in patients with retinopathy (p < 0.05) and correlated within the plasma with lipid peroxides (r = – 0.53, p < 0.04) and albumin thiols (r = 0.64, p < 0.01). The results suggest that diabetic patients, particularly with retinopathy, are under oxidative stress and have an increased thrombotic tendency with increased platelet reactivity and a reduction in prostacyclin stimulating factor.
Disabling Postural Hypotension Complicating Diabetic Autonomic Neuropathy
Authors: Stevens M. J. , Edmonds M. E. , Mathias C. J. , Watkins P. J.
Published: July 2009

A 35‐year‐old Type 1 diabetic man with severe disabling postural hypotension was studied for physiological abnormalities, precipitating factors, and effect of current treatment. A 24‐h blood pressure profile indicated a diurnal variation in systolic blood pressure with the lowest values recorded between 0100 and 0600 h, during which the patient often lost consciousness on standing (mean standing systolic pressure 78 mmHg at night vs 105 mmHg in the afternoon, p < 0.001). Food induced a profound fall in systolic pressure, both while supine and while standing erect. The systolic pressure fall during euglycaemia was 49 mmHg vs 3 mmHg during hypoglycaemia. Plasma noradrenaline and adrenaline levels were low during euglycaemia, but increased during hypoglycaemia. Therapeutic manoeuvres aimed at increasing heart rate (by atrial tachypacing) and reducing the peripheral pooling of blood (vasoconstricting drugs and gravity suit), together with the somatostatin analogue octreotide, proved ineffective. These observations demonstrate the phenomenon of post‐prandial exacerbation of postural hypotension in a Type 1 diabetic patient, and indicate that despite failure of conventional methods of treatment, hypoglycaemia increased plasma catecholamines and was effective in abolishing the blood pressure fall on standing.
The Socio‐economic Cost of Diabetic Complications in France
Authors: Triomphe A.
Published: July 2009

The costs to the community of diabetes and diabetic complications are large and the allocation of resources to prevention, diagnosis, and health care is controversial. The direct economic costs of diabetes are for the most part medical charges, whereas the indirect costs encompass loss of working days and a range of effects on the patient's quality of life. In the present study the monetary cost is estimated for a sample of 109 patients. Data on current state of health, socio‐economic characteristics and aspects of social and professional life were measured and expressed as the average medical annual cost of a patient in 1984. Medical expenditure categories included hospitalization, home visits, laboratory tests, pharmaceutical expenditure, and other medical and paramedical services. The average medical cost in 1984 was 12 178 French francs (FFr) for Type 1 diabetic patients and FFr 6908 for Type 2 diabetic patients. Omitting sick‐leave expense, the average cost of diabetic patients was close to the French national average of medical costs (or consumption) (FFr 7711 (Type 1), FFr 5892 (Type 2) vs FFr 6462 (national average)). Hospitalization constituted 33.9% (Type 1) and 40.1% (Type 2) of costs in France. Hospitalization for diabetic complications was not evaluated in this study and is poorly documented in France.
Natural History of Diabetic Complications: Early Detection and Progression
Authors: Deckert T. , Feldt‐Rasmussen B. , Borch‐Johnsen K. , Jensen T. , Kofoed‐Enevoldsen A. , Mathiesen E. R.
Published: July 2009

Until recently Type 1 diabetes has been characterized by a considerable degree of mortality, mainly associated with the development of diabetic nephropathy. Diabetic nephropathy is characterized by persistent proteinuria, decreasing glomerular filtration rate (GFR), increasing blood pressure, and morphological changes. Proteinuria represents a late stage in a prolonged process, which begins at the onset of Type 1 diabetes, when urinary albumin excretion is at the lower end of its normal range (< 10 mg 24‐h‐1). However, in those patients who will later develop persistent proteinuria, urinary albumin excretion increases exponentially at about 20% per year. These patients also tend to have rising blood pressure and falling GFR, higher rates of proliferative retinopathy and coronary heart disease, and elevated levels of cardiovascular risk factors. As intervention is possible in all these areas, identification of such patients is required and especially as the imposition of strict metabolic control may postpone or arrest progression to overt nephropathy. Where patients deteriorate despite such control the institution of early antihypertensive therapy and the effective management of end stage renal disease will bring further improvements in the prognosis of diabetic nephropathy.
Diabetic Renal Disease in Type 1 Diabetes: Aetiology and Prevention
Authors: Viberti G. C.
Published: July 2009

Diabetic renal disease affects a subset of about 35% of patients with Type 1 diabetes and is characterized by a triad comprising increased albuminuria, arterial pressure, and volume fraction of the mesangium. This leads to a decline in the glomerular filtration rate and ultimately end‐stage renal failure or premature cardiovascular mortality. Individuals at risk can be detected before the development of persistent proteinuria by screening for microalbuminuria which has proved predictive of clinical nephropathy in about 80% of cases. Microalbuminuria is often accompanied by subclinical increases in arterial blood pressure and plasma lipid levels and is usually not apparent until 5 years after stabilization of newly diagnosed diabetes. This latter finding suggests that microalbuminuria is an indicator of early disease rather than a marker of susceptibility to it. Recent evidence suggests that diabetic renal disease may be linked to a familial, possibly genetically determined, predisposition to arterial hypertension or to some factor closely related to the risk of hypertension. This underlying predisposition may be one of the mechanisms leading to severe glomerular damage and may help to explain why clinical renal disease only occurs in a subset of diabetic patients. A number of therapeutic interventions, ranging from strict blood glucose control to low‐protein diet and angiotensin‐converting enzyme inhibition are effective in reducing or preventing further increases in microalbuminuria. If current long‐term trials confirm that treatment of microalbuminuric diabetic patients prevents the onset of heavier persistent proteinuria secondary prevention of diabetic renal failure may become possible. The current criteria for diagnosis of diabetic nephropathy will then require revision.
Renal Functional Reserve in Diabetic Patients without Clinical Nephropathy: Comparisons with Renal Morphology
Authors: Dedov I. I. , Mukhin N. A. , Shestakova M. V. , Paltzev M. A. , Warshawskyi V. A. , Severgina E. S. , Nikolaev A. Yu.
Published: July 2009

The acute effect of a protein loading test (1.5 g kg‐1) on glomerular filtration rate (GFR) was examined in 10 Type 1 diabetic patients without clinical nephropathy to evaluate the renal functional reserve. GFR was measured before (baseline) and after (test) ingestion of the protein load. Two groups of diabetic patients were distinguished: those who exhibited normal renal reserve equal to that in healthy individuals (change in GFR 35 ± 17 (± SD)%) and those who had no renal reserve (change in GFR ‐20 ± 20%). These groups did not differ in the duration and control of diabetes nor in the level of urinary albumin excretion. However baseline GFR was 120 ± 34 and 209 ± 46 ml min‐1 in diabetic patients with and without renal reserve, respectively. Renal morphology revealed hilar glomerular lesions composed of severely expanded mesangium only in diabetic patients without renal reserve. Minimal structural nephropathy was observed in those who exhibited normal renal reserve. We suggest that the impaired response of GFR to protein loading precedes other subclinical manifestations of renal lesions in diabetic patients.
The Neurometer: Validation and Comparison with Conventional Tests for Diabetic Neuropathy
Authors: Masson E. A. , Boulton A. J. M.
Published: July 2009

The Neurometer is a portable constant current sine wave stimulator, which has recently been advocated for the quantification of peripheral nerve dysfunction by the measurement of detection thresholds for constant current stimulation. Stimuli are applied through surface electrodes at three frequencies and a forced choice method is used to determine the minimum amplitude for detection. The possible application of the Neurometer to the diagnosis and measurement of diabetic neuropathy was evaluated. The preliminary Neurometry results in comparison to those of conventional nerve testing techniques, including thermal and vibration detection thresholds, are discussed. It appears that the device may be a useful screening instrument which could give a fairly comprehensive idea of the functional integrity of different nerve fibre populations, and a full assessment takes only 10 to 15 min, in contrast to the conventional alternatives.
Auditory Brainstem and Middle Latency Evoked Responses in the Clinical Evaluation of Diabetes
Authors: Martini A. , Comacchio F. , Magnavita V.
Published: July 2009

The measurement of auditory brainstem evoked responses and middle latency evoked responses may improve the evaluation of diabetic neuropathy. Twenty diabetic patients were studied (12 males, 8 females), aged 21 to 63 years with normal hearing, together with 20 age‐ and sex‐matched normal subjects (10 males, 10 females). Auditory brainstem evoked responses were induced by rarefaction clicks of 0.1 ms at a repetition rate of 21.1 CPS and an intensity of 75 dB hearing level. Middle latency evoked responses were induced with clicks of 0.1 ms, a repetition rate of 7.7 CPS and an intensity of 75 dB hearing level. Diagnostic criteria were: a I‐V interval latency shift > 2SD of the control group for the auditory brainstem evoked response test or the interval difference of wave V > 0.2 ms. Middle latency evoked response was diagnostic if the latency of the Pa component was > 2SD of normals. Twenty‐five per cent of subjects had retrocochlear impairment (absence of I wave) even in the absence of symptoms. The combined technique of auditory brainstem evoked response and middle latency evoked response improved the detection rate of central nervous system dysfunction. Auditory brainstem response is important for detecting desynchronization of the auditory response, whereas middle latency evoked response detects abnormalities in the more rostral regions of the central nervous system. In conclusion, there is a role for auditory brainstem evoked response and middle latency evoked response in the global assessment of diabetic neuropathy.
A Study of Peripheral Diabetic Neuropathy. The Application of Age‐Related Reference Values
Authors: Armstrong F. M. , Bradbury J. E. , Ellis S. H. , Owens D. R. , Rosen I. , Sonksen P. , Sundkvist G.
Published: July 2009

The standardization of methodology and the provision of age‐related reference values have been addressed for the design of and interpretation of data from a multicentre neuropathy trial. Age‐related reference values were generated from 120 healthy volunteers. Vibration perception thresholds (VPT) deteriorated significantly with age (p < 0.001). Patients were selected on the basis of age‐related abnormal VPT and peroneal motor nerve conduction velocity. They were assessed at the beginning and end of a placebo run‐in period (baseline data). The coefficients of variation (CV%) for VPT at the medial malleolus (16.81 per cent, n = 316) and great toe (19.23 per cent, n = 313) were lower compared to results in healthy volunteers (29.7 per cent and 20.8 per cent, respectively, n = 49). The CV% for expiratory:inspiratory (E:I) ratio (4.82 per cent, n = 215), Valsalva manoeuvre (10.84 per cent, n = 249) and 30:15 ratio (7.73 per cent, n = 292) from patients corresponded to those recorded in volunteers (7.6 per cent, n = 45 11.0 per cent, n = 49 9.5 per cent, n = 48, respectively). Most patient values for VPT at the great toe fell beyond the 95 centile line for volunteers. E:I ratio for volunteers showed a more varible relationship with age, although patient values appeared to be located below the 5 centile line for volunteer data.
Myocardial Metabolism in Type 1 Diabetic Patients Without Coronary Artery Disease
Authors: Doria A. , Nosadini R. , Avogaro A. , Fioretto P. , Crepaldi G.
Published: July 2009

Myocaridal exchange of metabolic substrates was investigated in eight Type 1 diabetic patients with angiographically normal coronary arteries and seven normal control subjects, after an overnight fast. Simultaneous samples of arterial and coronary sinus blood were collected for analysis of the major metabolic substrates. Myocardial blood flow was measured by the thermodilution technique. Although the Type 1 patients were hyperglycaemic (10.0 ± 2.0 (± SE) mmol I‐1) myocardial glucose uptake was lower than in control subjects (27 ± 6 vs 42 ± 5 μmol min‐1 1.73 m‐2, p < 0.05). The net balance of lactate and pyruvate across the myocardium showed a net release in Type 1 patients (13.4 ± 2.7 μmol min‐1 1.73 m‐2 and 1.3 ± 0.2 μmol min‐1 1.73 m‐2, respectively) and a net uptake in control subjects (2.2 ± 0.7 μmol min‐1 1.73 m‐2 and 3.5 ± 0.3 μmol min‐1 1.73 m‐2, both p < 0.01). Myocardial uptake of ketone bodies was significantly higher in diabetic patients (37.0 ± 6.3) μmol min‐1 1.73 m‐2) than in control subjects (10.1 ± 3.4 μmol min‐1 1.73 m‐2, p < 0.01). Non‐esterified fatty acid (NEFA) uptake was significantly greater in the diabetic patients than in control subjects (44.1 ± 7.0) vs 24.1 ± 5.1 μmol min‐1 1.73 m‐2, p < 0.01). Net balance of glucose, lactate, and pyruvate across the myocardium was inversely and significantly related to that of NEFAs and ketone bodies (p < 0.01). Myocardial carbohydrate uptake is markedly impaired in Type 1 diabetic patients with angiographically intact coronary vessels. Ketones and NEFA represent the major fuel for the diabetic myocardium. Thus, in diabetes, myocardial lactate metabolism may be profoundly altered independently of coronary artery disease.
Catecholamines and Blood Glucose Control in Type 1 Diabetes
Authors: Bilo H. J. G. , Gans R. O. B. , Polee M. B. , van der Maten J. , Popp‐Snijders C. , Donker A. J. M.
Published: July 2009

To evaluate the influence of blood glucose control on serum catecholamine levels (which reflect both plasma and platelet levels), six healthy non‐diabetic subjects, seven well‐controlled Type 1 diabetic patients, and six poorly controlled Type 1 diabetic patients were studied before (baseline) and after standardized exercise. A significant correlation was found between serum noradrenaline and HbA1 at baseline (r = 0.53, p < 0.025) and after exercise (r = 0.71, p < 0.001). Similar results were found for serum adrenaline (r = 0.68, p < 0.005 and r = 0.61, p < 0.005, respectively) and consequently total serum catecholamine content (r = 0.65, p < 0.005 and r = 0.75, p < 0.001, respectively). However, no relationship was found between serum catecholamine levels and actual blood glucose levels, age, body mass index or insulin dose. A moderate correlation was found between systolic blood pressure and serum levels of noradrenaline and total catecholamines after exercise (r = 0.48 and r = 0.48, both p < 0.025).
Changes in Injection‐site Blood Flow and Plasma Free Insulin Concentrations in Response to Stress in Type 1 Diabetic Patients
Authors: Greenhalgh P.M. , Jones J.R. , Jackson C.A. , Smith C.C.T. , Yudkin J.S.
Published: July 2009

In order to test the effect of stress on injection‐site blood flow and blood glucose control, 16 C‐peptide negative patients were studied on a stress day, when a 30‐min Stroop Colour‐Word Test was completed, and a control day, when a cartoon was shown. Unmodified insulin was injected subcutaneously into the thigh before the test, and injection‐site blood flow measured throughout the experiment with a thermal clearance probe. Blood glucose and plasma free insulin, glucagon, growth hormone, cortisol, and catecholamines were measured at intervals before, during, and after stress. Patients showed a significant overall rise in injection‐site blood flow with the Stroop test from 4.1 (SD 1.6) to 5.2 (1.8) ml 100‐g−1 min−1 (increase 38.1 (37.8) %, p < 0.001). There was no overall significant difference between stress and control days in blood glucose or plasma free insulin levels, with differences in mean blood glucose levels during stress between the 2 days varying from −4.2 mmol l−1 to +6.3 mmol l−1 in individual patients. The increase in injection‐site blood flow with stress correlated significantly with the increase in plasma free insulin concentration both during (r = 0.55) and after stress (r = 0.71). Differences in blood glucose concentration between stress and control day for each patient showed strong correlation with differences in plasma free insulin both during (r = −0.73) and after stress (r = −0.79). Differences in counter‐regulatory hormones occurred but correlated poorly with blood glucose difference. Thus, stress affects the blood flow at the injection site, and this in turn affects insulin absorption. Most of the blood glucose response to stress is explained by changes in free insulin concentration.
Influence of Non‐carbohydrate Foods on Glucose and Insulin Responses to Carbohydrates of Different Glycaemic Index in Type 2 Diabetic Patients
Authors: Floch J.P. Le , Baudin E. , Escuyer P. , Wirquin E. , Nillus P. , Perlemuter L.
Published: July 2009

In order to study the influence of non‐carbohydrate foods on responses to carbohydrates during mixed meals, 30 Type 2 (non‐insulin‐dependent) diabetic patients followed a standardized diet for 5 consecutive days. On days 2, 3, 4, and 5, four different lunches were eaten in a randomized order. Lunches consisted of rice or glucose (50 g carbohydrate) eaten either alone, or as part of a mixed meal (32 g protein, 20 g fat). Glucose and insulin levels prior to the lunches did not differ significantly. Glucose and insulin responses differed (p < 0.001), responses to rice being lower than responses to glucose, and responses to the meal plus rice lower than responses to the meal plus glucose. The ratios of glucose responses to rice and glucose (glycaemic index) were similar (alone, 47 ± 4%; meal, 47 ± 4%; NS). The ratios of the insulin responses did not differ (78 ± 8 vs 96 ± 7%; NS). The blood glucose responses to mixed meals were lower than responses to the carbohydrates eaten alone, the ratios being similar (rice, 52 ± 3%; glucose, 58 ± 5%; NS). Serum insulin responses were however higher, and the ratios differed (172 ± 13 vs 138 ± 14%; p = 0.05). These results suggest that the glycaemic index of isolated carbohydrate foods can predict the relative response to mixed meals in the same individuals with Type 2 diabetes. They also support the insulin secretagogue effect of non‐carbohydrate foods, which may vary according to the source of carbohydrate in the meal.
Paradoxical Blood Flow Responses in the Diabetic Neuropathic Foot: an Assessment of the Contribution of Vascular Denervation and Microangiopathy
Authors: Stevens M.J. , Edmonds M.E. , Foster A.V.M. , Douglas S.L.E. , Watkins P.J.
Published: July 2009

Blood flow is abnormal in the diabetic neuropathic foot, and this may be of importance in the pathogenesis of complications. Arteriovenous shunting is increased, and blood flow through these channels may paradoxically decrease in response to local heating. Peak skin blood flow is also reduced in these patients. It is not known whether these blood flow abnormalities may reflect diabetic microangiopathy, or whether they simply reflect vascular denervation. The skin blood flow response to a local thermal stimulus was studied in four non‐diabetic patients with a unilateral traumatic neuropathy and foot ulceration. All showed a decrease in skin blood flow (to 68% of basal) at the great toe during local heating in the neuropathic limb, in contrast to the normal limb, in which blood flow increased to 180% of basal. Peak skin blood flow was also greatly reduced in the neuropathic limb, being only 29% of the normal limb. Neuropathy alone can be responsible for abnormal skin blood flow responses in the neuropathic foot.
The Effect of Callus Removal on Dynamic Plantar Foot Pressures in Diabetic Patients
Authors: Young M.J. , Cavanagh P.R. , Thomas G. , Johnson M.M. , Murray H. , Boulton A.J.M.
Published: July 2009

Clinical observation suggests that neuropathic foot ulceration frequently occurs beneath plantar callosities and in areas of high dynamic shear and vertical stress underneath the foot during walking. Seventeen diabetic patients had dynamic foot pressure measurements made before and after the removal of a total of 43 forefoot plantar callosities. Peak pressures (mean ± SE) in the treated areas were reduced by 26% from 14.2 ± 1.0 to 10.3 ± 0.9 kg cm−2 (p < 0.001), with reductions at 37 of the 43 sites and in all patients. Mean heel pressures were not significantly different (5.0 ± 0.6 vs 4.9 ± 0.6 kg cm−2). These results suggest that callus may act as a foreign body elevating plantar pressures and that a significant reduction in pressure is achieved by local chiropody treatment.
Restriction Fragment Length Polymorphisms at the GLUT4 and GLUT1 Gene Loci in Type 2 Diabetes
Authors: Alcolado J.C. , Baroni M.G.
Published: July 2009

Inherited abnormalities of the glucose transporters could explain many of the pathophysiological features of Type 2 diabetes including the strong familial predisposition to the disease. Previous studies have suggested a possible association between an allele of an Xba1 restriction fragment length polymorphism (RFLP) at the GLUT1 gene locus and Type 2 diabetes in Caucasian and Japanese subjects. In order to test this hypothesis further, population association studies were performed at the Xba1/GLUT1 and Kpn1/GLUT4 gene loci employing a group of diabetic patients with a strong family history for the disease. The frequencies of the two alleles at the GLUT1 locus were 0.28 and 0.72 in diabetic patients and 0.31 and 0.69 in control subjects. At the GLUT4 locus, the two alleles had frequencies of 0.24 and 0.76 in diabetic patients and 0.25 and 0.75 in control subjects. These differences were not statistically significant. The present study does not support the hypothesis that genetic variation within the GLUT1 or GLUT4 gene loci may be responsible for familial susceptibility to Type 2 diabetes.
Humoral Immune Response to a Yeast‐derived Hepatitis B Vaccine in Patients with Type 1 Diabetes Mellitus
Authors: Bouter K.P. , Diepersloot R.J.A. , Wismans P.J. , Meyling F.H.J. Gmelig , Hoekstra J.B.L. , Heijtink R.A. , van Hattum J.
Published: July 2009

The immune response following vaccination with a recombinant hepatitis B vaccine was investigated in 32 patients with Type 1 diabetes mellitus and compared with the outcome in 32 healthy age‐ and sex‐matched volunteers. Participants were vaccinated at 0, 30, and 180 days and in vivo immune response was determined at 30, 60, 90, 180, and 210 days. The number of responders (anti‐HBs > 1 IU I−1) was significantly lower (p < 0.05) among patients at 30 (2 vs 11), 60 (17 vs 26), 90 (20 vs 28) and 180 (22 vs 29) days. The number of patients protected (anti‐HBs > 10 IU I−1) was lower (p < 0.05) than the number of protected volunteers at 60 (5 vs 14), 90 (10 vs 19), 180 (15 vs 24), and 210 days (24 vs 31). After the complete course of vaccination 8 out of 32 patients were still unprotected against hepatitis B (p < 0.05). The anti‐HBs titre of responders at 210 days was 251 (20, 3162) (geometric mean (‐SD, +SD)) IU I−1 in patients and 1259 (126, 12589) IU I−1 in control subjects (p < 0.05). The HLA‐antigen DQw1 frequency in the diabetic low responders (anti‐HBs < 100 IU I−1) was 0.27 compared with 0.86 in diabetic adequate responders. No relation between anti‐HBs production and concentration of HbA1c could be demonstrated.
Classification of Symptoms of Hypoglycaemia in Insulin‐treated Diabetic Patients Using Factor Analysis: Relationship to Hypoglycaemia Unawareness
Authors: Hepburn D.A. , Deary I.J. , Frier B.M.
Published: July 2009

The allocation of some symptoms of acute hypoglycaemia to autonomic and neuroglycopenic groups has proved problematical, with possible misinterpretation of studies which depend upon the use of diverse symptom questionnaires. Two hundred and ninety‐five randomly selected insulin‐treated diabetic patients were asked to report the symptoms which they usually experienced and believed to be caused by hypoglycaemia. Sweating, trembling, inability to concentrate, weakness, hunger and blurred vision were the most frequently reported symptoms. To classify symptoms of hypoglycaemia objectively, Factor Analysis was used to identify related symptoms which grouped together. This resulted in five groups or clusters of symptoms, four of which could be denominated as groups with a presumed common aetiology, and were labelled: ‘neuroglycopenic’, ‘general malaise’, ‘autonomic’, ‘motor dysfunction’, and ‘sensory dysfunction’. The groups of symptoms derived by Factor Analysis were assessed in relation to partial or absent symptomatic awareness of hypoglycaemia based on historical evidence from the 295 insulin‐treated diabetic patients. Neuroglycopenic symptoms were reported more commonly by the patients who had reported partial awareness of hypoglycaemia (number of symptoms 2.6 ± 1.8 (mean ± SD)) than by the patients who had reported normal hypoglycaemia awareness (1.4 ± 1.5 symptoms) (p < 0.05). By contrast autonomic symptoms were reported less frequently by the patients who had reported absent hypoglycaemia awareness (1.3 ± 1.4 symptoms) than by those with normal awareness (2.2 ± 1.4 symptoms) (p < 0.05), which was similar to the number of autonomic symptoms reported by the patients who had partial hypoglycaemia awareness (2.1 ± 1.3 symptoms).
Increased Hypothalamic Neuropeptide Y Messenger RNA Levels in Two Rat Models of Diabetes
Authors: Jones P.M. , Pierson A.M. , Williams G. , Ghatei M.A. , Bloom S.R.
Published: July 2009

Elevated levels of immunoreactive hypothalamic neuropeptide Y have recently been reported both in streptozotocin‐induced diabetic rats and in the spontaneously diabetic BB rat. We have measured the levels of neuropeptide Y encoding messenger ribonucleic acid (mRNA) in both of these rat models to determine whether an increase in neuropeptide Y gene expression is a contributory factor to the increases in hypothalamic neuropeptide Y immunoreactive peptide content. In the hypothalami of both the spontaneously diabetic BB/E and the streptozotocin‐diabetic animals, neuropeptide Y mRNA showed significant elevations (to 204 ± 13% (± SE) and 387 ± 48% of control values, respectively, p < 0.01 for both). Our results demonstrate that two models of insulin‐deficient diabetes in the rat are associated with increased hypothalamic neuropeptide Y mRNA. Taken with the known effects of neuropeptide Y on food intake these results suggest that increased neuropeptide Y synthesis in the hypothalamus may be related to the hyperphagia seen in the diabetic condition.
A Cross‐sectional Study of Echocardiography Indices, Treadmill Exercise Capacity and Microvascular Complications in Nigerian Patients with Hypertension Associated with Diabetes Mellitus
Authors: Babalola R.O. , Ajayi A.A.
Published: July 2009

Associations between hypertension and cardiovascular complications of diabetes mellitus in Nigerians, were examined in a cross‐sectional study. 20 hypertensive‐diabetic patients, 16 hypertensive patients, 10 non‐hypertensive diabetic patients and 10 age‐ and sex‐matched healthy controls, underwent M‐mode and cross‐sectional echocardiography, and Bruce‐protocol treadmill exercise performance. Left ventricular (LV) mass indices (± SD) were significantly higher in hypertensive patients (164 ± 12gm2), diabetic (158 ± 17gm−2) and hypertensive diabetic patients (125 ± 129gm−2) compared with normal controls (111 ± 17gm−2) p < 0.01. However, the LV mass index in the hypertensive‐diabetic patients was significantly less than in hypertensive (p < 0.05) or normotensive diabetic patients (p < 0.05). Systolic cardiac contractility measured as fractional fibre shortening, was preserved in the hypertensive patients (24 ± 4%) compared with the healthy controls (23 ± 4%), but was depressed in diabetic patients (19 ± 3%) and to a greater extent in the hypertensive‐diabetic patients (15 ± 4% p < 0.01). Treadmill exercise tolerance time was reduced independently in hypertension (309 ± 73 seconds) or diabetes (321 ± 119 seconds), p < 0.05, but was further impaired in hypertensive‐diabetic patients (289 ± 110 seconds) p < 0.01 compared to the healthy controls (490 ± 156 seconds). The patients with hypertension and diabetes had a greater degree of proteinuria (p < 0.001) and a higher frequency of retinopathy (p < 0.001), in comparison to those with hypertension or diabetes alone.
Risk Factors for Peripheral Vascular Disease in Hypertensive Subjects with Type 2 Diabetes Mellitus
Authors: Alcolado J.C. , Pacy P.J. , Beevers M. , Dodson P.M.
Published: July 2009

Possible factors predisposing to peripheral vascular disease (PVD) in hypertensive subjects with Type 2 diabetes mellitus were studied. Details of age, sex, duration of diabetes, blood pressure, and smoking habit were recorded in 180 subjects of either White, West Indian Black or Asian ethnic origin. Glycosylated haemoglobin, fasting serum total cholesterol, total high density lipoprotein (HDL), HDL2, low density lipoprotein (LDL‐cholesterol), and triglycerides were measured in all subjects. Peripheral vascular disease was defined as an ankle/brachial systolic pressure < 1.0 as measured by the Doppler technique. Multivariate analysis was performed and the following factors were identified as being strongly associated with the presence of PVD with a statistical significance of p < 0.001; LDL‐cholesterol, total HDL‐cholesterol, age, male sex, diet or oral hypoglycaemic therapy, diastolic blood pressure, and of p < 0.003; systolic blood pressure. When blood pressure was excluded from the analysis the other factors retained their predictive value. We conclude that hypertension and dyslipidaemia are important risk factors for peripheral vascular disease in Type 2 diabetes mellitus.
A Double Blind Study of the Effect of Acipimox on Serum Lipids, Blood Glucose Control and Insulin Action in Non‐obese Patients with Type 2 Diabetes Mellitus
Authors: Fulcher G.R. , Catalano C. , Walker M. , Farrer M. , Thow J. , Whately‐Smith C.R. , Alberti K.G.M.M.
Published: July 2009

Hyperlipidaemia, in particular raised concentrations of serum triglycerides, together with raised plasma non‐esterified fatty acid concentrations, is common in patients with Type 2 (non‐insulin‐dependent) diabetes mellitus and may be associated with insulin insensitivity. Thirty non‐obese Type 2 diabetic patients (15 controlled with diet alone and 15 with diet plus oral sulphonylurea therapy) were therefore recruited to take part in a double‐blind, randomized, crossover comparison of acipimox (250 mg three times daily for 3 months) and placebo. Serum lipids, blood glucose control, insulin sensitivity, and glucose tolerance were measured before and after each treatment period. There was a significant decrease in serum triglycerides (2.05 ± 1.08 vs 2.91 ± 1.75: p < 0.005), cholesterol (5.66 ± 1.02 vs 6.26 ± 1.17: p = 0.0005), and apoprotein B (1.32 ± 0.23 vs 1.44 ± 0.25: p < 0.05) while HDL cholesterol and apoprotein A‐1 concentrations were unchanged. There was no change in blood glucose control measured by fasting glucose, insulin, and HBA1 concentrations, but there was a significant improvement in insulin action assessed by glucose—insulin infusion. Although plasma non‐esterified fatty acid concentrations were lower during the oral glucose tolerance test after acipimox, there was no difference in either the peak or 2‐h plasma glucose concentrations and the total area under the glucose curve did not change. Acipimox was well tolerated and no patients withdrew from the study for drug‐related symptoms. Thus, acipimox effectively lowers serum cholesterol and triglycerides in patients with Type 2 diabetes without adversely altering blood glucose control, and appears to improve insulin sensitivity.
T‐Cell Receptor Constant β Chain Polymorphisms and Susceptibility to Type 1 Diabetes
Authors: Hibberd M.L. , Millward B.A. , Wong F.S. , Demaine A.G.
Published: July 2009

Several groups have previously shown that the T‐cell receptor (TCR) constant‐β (Cβ) chain locus is associated with susceptibility to Type 1 diabetes, although other studies have failed to show this. We have extended these studies by investigating 125 individuals with Type 1 diabetes and failed to confirm the significantly increased frequency of the 10;9.2 kb TCR‐Cβ/Bgl‐II genotype in our patient population. However, further analysis showed that the 10;9.2 kb TCR‐Cβ genotype was significantly increased in those patients with no microvascular complications after 20 years of diabetes compared to those patients with complications (proteinuria, overt neuropathy, and moderate or severe retinopathy) 69.2% vs 31.7%, respectively, p < 0.005 Pc = 0.025). Similar results were also found in a second group of 74 patients who were analysed in the same way. Hence, the failure of some investigators to confirm the association between TCR‐Cβ and Type I diabetes may be due to heterogeneity in the patient populations being studied.
A Survey of Lower Limb Amputation in Diabetic Patients
Authors: Deerochanawong C. , Home P.D. , Alberti K.G.M.M.
Published: July 2009

A retrospective survey of non‐traumatic and non‐neoplastic lower limb amputations in Newcastle upon Tyne during 1989–91 was performed. Hospital data were cross‐checked with the local limb fitting centre to ensure 100% ascertainment. The diabetic patients were found to be 39% of amputees and 42% of operations (all levels). Incidence of diabetes amputation was 5.7 per 100000 population per year. Fifteen percent of the diabetic patients had diabetes first diagnosed when they were admitted for amputation. For the known diabetes patients, 46% were under diabetes care by general practitioners only. Forty‐seven percent of the patients who were under the care of a hospital service for diabetes had incomplete foot examination and assessment. Mortality rate within 30 days after diabetic amputation was 10% and median life expectancy following amputation was 22 months. It seems likely that assessment and management of the diabetic foot remains suboptimal in Newcastle, and that protocols and audit of care could lead to improvements without additional resources.