bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Presentation and Management of Diabetic Neuropathy and Foot Ulceration
Authors: Boulton A. J. M.
Published: July 2009

A simple classification of the more common neuropathies is presented. The most frequent disorder in diabetes is a symmetrical sensory polyneuropathy in the lower limbs. Acute sensory polyneuropathies frequently follow sudden metabolic disturbance although there may be little evidence of neurological abnormalities on clinical examination. Similar symptoms occur with chronic sensory polyneuropathy but onset is gradual and this condition may persist for years with only minor symptoms. A significant proportion of patients with chronic polyneuropathies have few if any symptoms and are only diagnosed by careful clinical examination. An approach to the diagnosis and management of symptomatic sensory polyneuropathy is suggested. Sensory loss, and the possible complication of vascular dysfunction, greatly increases the risk of insensitive foot lesions in diabetic patients. Some may progress to the insensitive foot without prior evidence of neuropathy. Regular and thorough examination is therefore the only way to identify patients at risk who then require education in preventative foot care. The identification of such patients and the clinical presentation and management of foot ulcers is discussed.
Assessment of Basal and Stimulated Sweating in Diabetes using a Direct‐reading Computerized Sudorometer
Authors: Levy D. M. , Reid G. , Abraham R. R. , Rowley D. A.
Published: July 2009

Abnormalities of eccrine sweating are thought to be common in diabetes. We describe a ventilated‐capsule sudorometer for the continuous measurement of basal and stimulated sweat secretion. It is sensitive (detecting as little as 200 ng water vapour), precise, and stable. Since it measures dewpoint rather than relative humidity, it can be calibrated to read sweat volumes directly and independently of ambient temperature and humidity. Preliminary studies using this technique show that basal skin water loss is significantly diminished in patients with established diabetic neuropathy (0.91 ±0.18 g (± SD) cm‐2 h‐1) compared with normal subjects (1.21 ± 0.39 g cm‐2 h‐1; p = 0.04) and non‐neuropathic diabetic subjects (1.32 ± 0.48 g cm‐2 h‐1; p = 0.04), and that local sweating induced by iontophoresis of 10 g I‐1 acetylcholine is significantly reduced in diabetic subjects up to 5 min of recording (0.95 ± 0.43 vs 1.26 ± 0.40 mg; p = 0.02). In neuropathic subjects both low‐ and high‐amplitude responses are seen, the latter probably representing denervation supersensitivity. Further studies with sensitive sudorometry should enable the mechanisms of these abnormal responses to be established.
Diabetes and Arterial Disease
Authors: Gries F. A. , Koschinsky Th.
Published: July 2009

Macroangiopathy (or atherosclerosis) is a common and chronic complication in diabetic patients. Unlike other diabetic complications, atherosclerosis is not unique to diabetes, confounding analysis of its relationship with the diabetic condition. Evidence of an independent role for diabetes in the development of atherosclerosis remains equivocal. The main determinant of macrovascular disease may be an interaction between diabetes and the aging process. Similarly the question of a relationship between macrovascular disease and good metabolic control remains unanswered. Macroangiopathy in diabetic populations seems to be related to similar predictors and pathological mechanisms operating in the general population. However, after analysis of these common risk factors for macroangiopathy, a diabetes‐specific risk remains. Low‐density lipoprotein metabolism is markedly disturbed in poorly controlled diabetic patients. This is manifest as a concert of actions which increase formation of foam cells and fatty streaks. The next step in the atherosclerotic process, the formation of fibrous plaques, may be associated with the platelet hyperactivity seen in diabetes. This may promote overshooting of repair mechanisms at the vessel wall. Release of a specific diabetic serum growth factor from the platelets may be responsible for the later stages of fibrous plaque development and the increased atherosclerotic risk in diabetes.
Risk Factors of Cardiovascular Death in Diabetic Patients
Authors: Janeczko D. , Czyzyk A. , Kopczynski J. , Krzyzanowski M.
Published: July 2009

In 1974 a cross‐sectional study was conducted on 4591 out‐patients (2095 males and 2496 females) aged 18–67 years, with diabetes of 1–10 years duration, and cardiovascular fatalities followed for 10 years. A multiple logistic regression was then performed on total cardiovascular deaths, deaths from ischaemic heart disease, and from stroke on selected baseline variables related to the course and control of diabetes, selected symptoms of macroangiopathy, and other risk factors, separately for insulin‐treated and non‐insulin‐treated patients. Hyperglycaemia, proteinuria, arterial hypertension, various symptoms of ischaemic heart disease, age, and current cigarette smoking were found to be important predictors of cardiovascular mortality, more so in non‐insulin‐treated than in insulin‐treated patients. Proteinuria and arterial hypertension carried a greater risk in females than males, but the opposite was true for the signs and symptoms of ischaemic heart disease. Relative body mass was found to correlate inversely with probability of cardiovascular death among insulin‐treated males but not in non‐insulin‐treated males, whereas duration of diabetes was a significant factor only among non‐insulin‐treated females.
Nocturnal Subcutaneous Hyperaemia in the Lower Leg and Foot of Type 1 Diabetic Patients
Authors: Kastrup J. , Sindrup J.H. , Christiansen E. , Jelnes R. , Wroblewski H. , Nørgaard T. , Parving H.‐H.
Published: July 2009

Nocturnal fluctuations in subcutaneous blood flow in the lower leg and foot were measured during sleep in Type 1 diabetic patients without autonomic neuropathy. Subcutaneous blood flow was measured, simultaneously, 100 mm above the malleolus on the medial aspect of the right lower leg and at the dorsum of the left foot in 10 diabetic patients, and on the right lower leg only in 10 normal human subjects over 12–20 h. The 133Xe wash‐out technique, portable CdTe (Cl) detectors and a portable data storage unit were used. The tracer depots were applied by means of the epicutaneous, atraumatic labelling technique. In diabetic patients, subcutaneous blood flow increased 102 ± 68% in the lower leg and 111 ± 98% in the foot at 113 ± 32 min and 107 ± 37 min, after going to sleep. The hyperaemic phase lasted 128 ± 43 min and 150 ± 42 min, respectively. The hyperaemic response was not different from that in the control subjects (89 ± 61%). There was no significant correlation between the absolute hyperaemia in the leg and that in the foot. In conclusion, Type 1 diabetic patients without autonomic neuropathy have normal nocturnal hyperaemia during sleep.
The Effect of Intravenous Metformin on Glucose Metabolism During Hyperglycaemia in Type 2 Diabetes
Authors: Sum C.‐F. , Webster J.M. , Johnson A.B. , Catalano C. , Cooper B.G. , Taylor R.
Published: July 2009

A stepped intravenous metformin infusion was used in conjunction with the hyperglycaemic clamp technique to study the dose‐response relationship of plasma metformin concentration with hepatic glucose production and peripheral glucose disposal in nine patients with Type 2 diabetes. The study was of double‐blind crossover design, using NaCl infusion as control. Plasma metformin concentrations spanning the therapeutic range (1.64 ± 0.13 mg I−1 and 6.57 ± 0.61 mg I−1) were achieved. No differences in peripheral glucose disposal were demonstrated when compared with NaCl infusion (3.4 ± 0.1 vs 3.6 ± 0.2 (±SE) mg kg−1 min−1 and 3.4 ± 0.2 vs 3.3 ± 0.2 mg kg−1 min−1, respectively). There was also no difference in basal hepatic glucose production during metformin and NaCl infusion (2.7 ± 0.3 vs 2.8 ± 0.2 mg kg−1 min−1). No acute effect of metformin on hepatic glucose production or peripheral glucose disposal was observed, implying that a chronic persistent effect is more important in these respects than immediate effects consequent upon changes in plasma drug level.
The 1‐h 50‐g Glucose Challenge Does Not Predict Large‐for‐Gestational‐Age Infants
Authors: Phillipou G.
Published: July 2009

The relationship between the 1‐h 50‐g glucose challenge performed at 24–28 weeks and subsequent birth of a large‐for‐gestational‐age infant was examined in a cohort of 368 Europid women who had no pre‐existing medical condition and experienced no pregnancy complications. The results established that the 1‐h 50‐g glucose challenge blood glucose level had no predictive power with respect to the birth of a large‐for‐gestational‐age infant. However, the 1‐h blood glucose value was found to be significantly related to maternal height, weight and age, indicating that its level also represents processes unconnected to glucose intolerance. The study findings also re‐confirmed the importance of parity, height, sex, and weight as determinants of large‐for‐gestational‐age infants.
An Audit of Lower Limb Arteriography in Diabetic Patients
Authors: Mansell P.I. , Gregson R. , Allison S.P.
Published: July 2009

The outcome of 83 diabetic patients with peripheral vascular disease who underwent arteriography between 1984 and 1988 was reviewed. Angioplasty was possible in 42 legs and was technically successful in 31 but led directly to clinical improvement in only 15. Five of 20 patients referred for vascular surgery also improved. Factors associated with a clinically successful outcome were presentation with claudication, palpable pulses in the contralateral foot, and radiographic evidence of either a short proximal lesion or 2–3 vessel run‐off. Median life expectancy following arteriography was 36 months. The median time to amputation was 21 months and median survival with both life and limb intact was only 13 months.
Impotence in Diabetes: Aetiology, Implications for Treatment and Preferred Vacuum Device
Authors: Ryder R.E.J. , Close C.F. , Moriarty K.T. , Moore K.T.H. , Hardisty C.A.
Published: July 2009

In an assessment of the contributions of autonomic neuropathy and vascular disease to the aetology of male impotence in diabetes, evidence of autonomic neuropathy was identified in 23/39 (59%) individuals complaining of impotence. Thirteen of 26 men aged < 60 years tested with an intracorporeal injection of papaverine experienced little or no response and seven had tumescence but no rigidity. Radioisotope phallography demonstrated vascular disease in six of these seven, suggesting evidence of a vascular component in 19/26 (73%). Only one patient had non‐organic impotence. Overall, evidence of vascular disease alone was demonstrated in 10/26 (38%), vascular disease plus autonomic neuropathy in 9/26 (35%), and autonomic neuropathy alone in 6/26 (23%). Many diabetic men complaining of impotence appear to have a significant vascular component which renders intracorporeal papaverine treatment ineffective. We compared the performance of a vacuum constriction‐band (Erecaid) and condom‐type (Synergist) device in 10 randomly selected men from this group. The devices, provided in random order for 5 months each, were assessed by questionnaire and interview of both the patient and partner. Two couples defaulted and another could use neither device. Although erectile capacity could be restored in the remainder, subsequent intercourse was only deemed satisfactory to both partners in five couples, who unanimously preferred the constriction‐band device. In treatment with vacuum devices the constriction‐band type seems to be the device of choice; the condom type should probably be reserved for those unable to use the constriction‐band type.
Insulin Injection Site Tissue Depths and Localization of a Simulated Insulin Bolus Using a Novel Air Contrast Ultrasonographic Technique in Insulin Treated Diabetic Subjects
Authors: Thow J.C. , Coulthard A. , Home P.D.
Published: July 2009

Subcutaneous adipose tissue depth was measured in 50 randomly selected Type 1 diabetic patients by real‐time ultrasound at five standard sites commonly used for injection. Tissue depths were often less than the length of the standard insulin syringe needle (12–13 mm) at the arm and thigh injection sites, especially in men. Thus, if the currently recommended perpendicular injection technique were to be employed, there would, in theory, be an appreciable risk of intramuscular insulin deposition. In order to determine the true site of deposition in those at risk (injection site tissue depth of < 12 mm), a novel air‐contrast ultrasound imaging technique was developed. A mixture of 0.1 ml of air and 0.2 ml of sterile 0.9% saline was self‐injected into an anterior thigh site by 30 subjects using their usual technique. The site of the resultant tissue depot was located by ultrasound. Sixty‐three percent of the depots were localized to true subcutaneous tissue and the remaining 37% to between the fascial planes overlying muscle. None of the subjects proved to be injecting into muscle. These results contrast with predictions of the risk of intramuscular injection made from the ultrasound measurement of subcutaneous tissue alone at the anterior and lateral thigh sites of, respectively, 100 and 97% for men and 42 and 37% for women. Although 11 of the 30 subjects claimed to be using a full‐depth perpendicular injection technique, on direct observation only four proved to be injecting perpendicularly and none of these to the full depth of the needle. These results suggest that the potential for intramuscular injection in insulin‐treated diabetic patients is high, particularly in men, but that in practice this risk is minimized by the use of an appropriate injection technique. Promotion of a single injection technique is clearly inappropriate and patients should instead be encouraged to adopt a method that is suited to their individual circumstances.
The Quality and Relevance of Peripheral Neuropathy Data on a Diabetic Clinical Information System
Authors: Jones R.B. , Gregory R. , Jones E.W. , Kerr D. , Allison S.P. , McLeod A. , Titterington D.M. , Hedley A.J.
Published: July 2009

Routinely collected peripheral neuropathy data entered on a diabetic clinical information system since 1979 have been audited for completeness, consistency, accuracy (inter‐observer variation), validity by comparison with biothesiometry, and relevance by life table analysis for foot ulceration. Peripheral neuropathy was defined by a neuropathy disability score ≥4. The data were 98% complete. Forty‐nine of 3405 (1.4%) had inconsistent records. Agreement between observers for clinical examination was significant (p<0.05) for aggregate neuropathy score and its individual components except the knee jerk: Kappa score for observer variation for neuropathy score 0.56 (95% confidence interval 0.36–0.76). There was good agreement between neuropathy defined as aggregate score ≥4, and as combined vibration perception thresholds for both feet >60 V: Kappa statistic 0.62 (95% confidence interval 0.44–0.80). The chance of developing a foot problem in 3 years increased from 3% for patients with a score of zero to 45% for people with a score of between 9 and 12. We conclude that the calculation of a clinical neuropathy score is a simple, valid and relevant method for diabetes care both in hospital and the community. When combined with palpation of peripheral pulses most patients at risk of foot ulceration can be identified allowing targeting of preventive chiropody and orthotic resources.
Prescribing and Dispensing of Insulin: Margins for Error?
Authors: Page M.D. , Stephenson C. , Pope R.M. , Bodansky H.J.
Published: July 2009

To investigate recent anecdotal reports of incorrect insulin dispensing, we compared retail pharmacists' and doctors' understanding of commonly used insulin brands. Eighty pharmacists, 29 general practitioners (GPs), and 31 junior hospital doctors were interviewed and completed a questionnaire concerning the duration of action and formulation of 17 insulins. Views on dispensing of alternative insulins were sought from the pharmacists. Fifteen insulin pairs in two columns, ‘insulin prescribed’ and ‘dispense instead’, were presented and pharmacists and doctors asked if substitution was appropriate. Mixtard, Penmix and Actrapid were the best understood insulins, Insulatard, Humulin Zn and Protaphane the worst. Both GPs (p = 0.014) and hospital doctors (p < 0.001) scored better than pharmacists. No pharmacist stated that they would routinely dispense alternative insulin, 27 out of 80 not even in an emergency, though 37 were prepared to do so in such a situation after checking, usually with a doctor or in the relevant literature. Sixteen pharmacists, 24 GPs, and all 31 hospital doctors completed the section on insulin pairs but accuracy at identifying appropriate substitutions was poor. These findings coupled with confusing insulin nomenclature may lead to dangerous dispensing errors.
Pre‐ and Postoperative Glucose Levels for Eliciting Hypoglycaemic Responses in a Patient with Insulinoma
Authors: Vea H. , Jorde R. , Sager G. , Vaaler S. , Sundsfjord J. , Revhaug A.
Published: July 2009

Counterregulatory hormones and hypoglycaemic symptoms were studied during a gradual decline in plasma glucose in a 66‐year‐old man before and 9 weeks after removal of an insulin‐producing tumour. Before surgery the adrenaline started to respond first at plasma glucose 2.8 mmol I−1. He reported no autonomic symptoms although plasma glucose fell to 2.3 mmol I−1 with a corresponding adrenaline rise to 4.64 nmol I−1. After surgery adrenaline responded at a plasma glucose of 3.7 mmol I−1 and he started to sweat and tremble at a plasma glucose of 3.1 mmol I−1 (corresponding adrenaline 2.63 nmol I−1). The lack of autonomic symptoms preoperatively may indicate adrenaline insensitivity, possibly as a result of repeated hypoglycaemia.
Phrenic Neuropathy in Association with Diabetes
Authors: White J.E.S. , Bullock R.E. , Hudgson P. , Home P.D. , Gibson G.J.
Published: July 2009

We report the case of a 51‐year‐old man who presented with breathlessness on exertion and orthopnoea in association with Type 2 diabetes mellitus. Investigation showed bilateral diaphragmatic paralysis due to phrenic neuropathy. There was no evidence of neuropathy or microvascular disease elsewhere. Phrenic neuropathy may be an important, albeit rare, complication of diabetes and diaphragmatic function should be considered in any patient with unexplained breathlessness and orthopnoea.
Arterial Wall Compliance in Diabetes
Authors: Lehmann E.D. , Gosling R.G. , Sönksen P.H.
Published: July 2009

A non‐invasive Doppler ultrasound technique, based on the measurement of pulse wave velocity along the aorta, has been used to deduce aortic compliance in 25 Type 1 and 25 Type 2 diabetic patients. Thirteen of the Type 1 diabetic group had their compliance measured within 1 year of diabetes first being clinically diagnosed. All compliance values were normalized for age and sex variations using data previously obtained from over 600 normal, non‐diabetic subjects (mean normalized compliance ± SD; 100 ± 15%). The results show that Type 1 diabetic patients have significantly more distensible aortas (132 ± 26%) than their age‐ and sex‐matched non‐diabetic counterparts (100 ± 12%) (p < 0.01), while Type 2 diabetic patients have significantly stiffer aortas (74 ± 21%) than their age‐ and sex‐matched non‐diabetic counterparts (100 ± 18%) (p < 0.01). The young Type 1 diabetic patients measured within 1 year of diagnosis have aortas ranging up to 78% more distensible (151 ± 15%) than their age‐ and sex‐matched non‐diabetic controls (100 ± 11%) (p < 0.001). These results support findings by other groups that adult diabetic patients have less distensible arteries than normal, but contradict reports in the literature dating back over 20 years that diabetic children have stiffer arteries than normal children.
A Comparison of the Predictive Power for Overall Blood Glucose Control of a ‘Good’ Fasting Level in Type 2 Diabetic Patients on Diet Alone or with Oral Agents
Authors: Trovati Mariella , Burzacca S. , Mularoni E. , Massucco P. , Cavalot F. , Mattiello L. , Anfossi G.
Published: July 2009

The European NIDDM Policy Group classifies both fasting and post‐prandial blood glucose concentrations into ‘good’, ‘acceptable’, and ‘poor’ categories. The aim of the present study was to evaluate whether a ‘good’ fasting blood glucose concentration in Type 2 diabetic patients on diet or diet + oral hypoglycaemic agents is able to predict ‘good’ blood glucose values throughout the day, and therefore to discover whether or not it is necessary to perform blood glucose profiles in Type 2 diabetic patients when their fasting value is ‘good’. Capillary blood glucose profiles (n = 417) were measured in 287 Type 2 diabetic patients, on diet alone (279 profiles), or on diet + tablets (138 profiles). We observed that 66% of profiles on diet and 44% of profiles on diet + tablets had only ‘good’ blood glucose concentrations (p < 0.001). Eleven percent of profiles on diet and 30% of profiles on diet + tablets included ‘poor’ blood glucose concentrations (p < 0.001). Despite matched fasting blood glucose concentrations (diet 5.69 ± 0.04 (±SE) vs tablets 5.75 ± 0.05 mmol I−1), levels were higher in the diet + tablet treated patients at all later time‐points (p < 0.01–0.001). HbA1c was significantly higher in tablet‐treated patients than in patients on diet alone (6.6 ± 0.1 vs 5.9 ± 0.1%, p < 0.001), and correlated with the mean blood glucose concentration (r = 0.43, p< 0.001) but not with the fasting glucose concentrations. We conclude that a ‘good’ fasting blood glucose concentration is more predictive of good overall control in patients on diet alone than in patients on diet plus oral agents.
Changes in Renal Function During Acute Insulin‐induced Hypoglycaemia in Patients with Type 1 Diabetes
Authors: Patrick A.W. , Hepburn D.A. , Swainson C.P. , Frier B.M.
Published: July 2009

The effect of acute hypoglycaemia on renal function was examined in eight male patients with Type 1 diabetes who had normal urinary albumin excretion. Insulin was given as a bolus intravenous injection (0.125 U kg−1) and plasma glucose fell to a nadir of 1.6 (SE 0.2) mmol I−1, with all patients experiencing an acute autonomic reaction. Renal plasma flow fell from 674 (106) to 540 (198) ml min−1 during hypoglycaemia (p < 0.01) and returned to 655 (181) ml min−1 (NS vs baseline). Glomerular filtration rate (GFR) declined from 143 (23) to 110 (36) ml min−1 during hypoglycaemia (p < 0.02), rising to 150 (44) ml min−1 in the recovery period (NS vs baseline). The urinary flow rate and urinary albumin excretion rate both fell significantly in response to hypoglycaemia (10.6 (1.2) to 4.7 (1.1) ml min−1; p < 0.002, and 46.2 (10.6) to 26.0 (10.5) μg min−1, respectively). Urinary dopamine excretion also declined, from 322 (37) to 211 (29) μmol min−1 (p < 0.005) but sodium excretion was unchanged. Plasma adrenaline concentration (0.2 (0.03) to 1.7 (0.4) nmol I−1; p < 0.01) and plasma renin activity (0.49 (0.13) to 1.08 (0.17) ng‐Ang I ***l−1 h−1; p < 0.01) increased during hypoglycaemia, but changes in plasma noradrenaline and angiotensin II levels did not attain significance. These acute changes in renal function, observed during hypoglycaemia in diabetic patients, may result from direct stimulation of the efferent sympathetic nerves to the kidney, complemented by the hormonal changes induced by hypoglycaemia.
Dietary Recommendations for People with Diabetes: An Update for the 1990s
Authors:   Nutrition Subcommittee of the British Diabetic Association's Professional Advisory Committee
Published: July 2009

The broad principles of the 1982 British Diabetic Association dietary recommendations remain valid. For the overweight, reduction in energy intake remains the most important aim. Carbohydrate should make up about 50–55% of the dietary energy intake, the majority of this coming from complex sources, preferably foods naturally high in dietary fibre or hydrolysis resistant starch. Up to 25 g of added sucrose may be allowed, provided it is part of a diet low in fat and high in fibre, and that it substitutes for an isocaloric amount of fat or high glycaemic index food or other nutritive sweeteners. Some high‐carbohydrate diets have been shown to worsen blood glucose control and serum lipid abnormalities. Some previous recommendations for fibre intake have proved unrealistically high and of limited value. A modest increase to 30 g day−1, concentrating on soluble fibre, is recommended. Reduction of fat intake to 30–35% of energy intake remains an important goal which should help to reduce the incidence of cardiovascular disease in people with diabetes and aid weight loss. Of this only 10% of total energy should be saturated fat, 10% polyunsaturated fat, and 10–15% may be mono‐unsaturated fat. The latter has been shown to provide a useful alternative energy source which may have beneficial effects on blood glucose control and serum lipids. Cholesterol intake should not exceed 300 mg day−1. Protein should comprise about 10–15% of energy intake. Reduction in intake of protein and associated nutrients may help to slow down progression of nephropathy. Limitation of salt intake to 6 g day−1 is recommended. Reduction in fat intake may be relatively more important in Type 2 diabetic patients, whereas limitation in protein intake may be more important in Type 1 diabetes.
Breast Feeding and the Development of Type 1 Diabetes Mellitus
Authors: Kyvik K.O. , Green A. , Svendsen A. , Mortensen K.
Published: July 2009

A case‐control study was conducted to study the proposed inverse relationship between breast feeding and incidence of Type 1 diabetes mellitus. All Danish diabetic men born in Copenhagen during 1959–1964 and/or residing there for the first year of life (n = 119) were identified and a search made for their post‐natal health visitor records. These include data on birth weight, birth length, immunizations, and feeding habits. A total of 77 cases were re‐identified. No differences were found with respect to clinical characteristics between these cases and those not identified. For each diabetic subject, two control children with date of birth identical to the diabetic cases were drawn from health visitor records. Cases and controls did not differ with respect to maternal age, or birth weight or length. Overall, the statistical analysis failed to confirm the hypothesis of an association between duration of breast feeding and subsequent diabetes risk.
Intraregional Differences in the Absorption of Unmodified Insulin From the Abdominal Wall
Authors: Frid A. , Linde B.
Published: July 2009

Absorption of subcutaneously injected unmodified human125I‐insulin (5 U; 100 U ml−1) was studied concurrently from three areas of the abdominal wall (120 mm above, 120 mm lateral to, and 40 mm below the umbilicus), and one area of the thigh (upper midline), in nine Type 1 diabetic patients of normal body weight, and from deep (2 mm above muscle fascia) and superficial (3 mm beneath skin surface) sites in abdominal wall and thigh in 11 Type 1 diabetic patients. The absorption rates were followed continuously for 3 h with the patient in the supine position. Whereas 125I‐insulin disappeared considerably faster from the site above the umbilicus than from sites below or lateral to the umbilicus or from the thigh (residual radioactivities after 175 min: 36 ± 4 vs 49 ± 5, 54 ± 2, and 62 ± 4 (±SE) %, respectively; p < 0.05 or better), no significant differences were found between deep and superficial sites in either abdominal wall or thigh. The results suggest that insulin absorption rates from subcutaneous injection sites within the abdominal wall differ sufficiently for this to be of clinical importance.
Metabolic Effects of Monomeric Insulin Analogues of Different Receptor Affinity
Authors: Robertson D.A. , Singh B. M. , Hale P. J. , Jensen I. , Nattrass M.
Published: July 2009

The effects of two monomeric insulin analogues of differing receptor affinities (human insulin = 100 %) B9Asp‐B27Glu‐insulin (18 %) and B10Asp‐insulin (327 %) were each compared with human insulin in two groups of 10 normal men when infused at equimolar low doses (1.0 and 2.0 pmol kg−1 min−1). The metabolic clearance rate under steady state conditions was highest for the analogue with the highest receptor affinity, 26.8 ± 0.8 (±SE) vs 19.8 ± 0.7 ml kg−1 min−1 for insulin (p< 0.001), and lowest for the analogue with the lowest receptor affinity, 13.3 ± 0.8 vs 25.1 ± 2.0 ml kg−1 min−1 for insulin (p < 0.001). The apparent plasma half‐life was prolonged for the low affinity analogue compared with human insulin (12.6 ± 0.6 vs 1.9 ± 0.2 min, p < 0.001), and significantly shorter for the higher affinity analogue (1.6 ± 0.1 vs 3.1 ± 0.4 min, p < 0.05). The three insulins gave similar falls in blood glucose, non‐esterified fatty acids, glycerol, and total ketone bodies over the infusion period. Thirty minutes after the end of the infusion, the rise in blood glucose for the low affinity analogue was significantly less than for human insulin (0.5 ± 0.2 vs 0.9 ± 0.1 mmol I−1, p < 0.05). Despite different receptor affinities, these analogues have similar in vivo effects in normal men, but the time‐course of their actions may differ when they are infused intravenously.
‘Spontaneous’ Platelet Aggregation in Whole Blood in Diabetic Patients With and Without Microvascular Disease
Authors: Hendra T. J. , Yudkin J. S.
Published: July 2009

Consistent abnormalities of agonist‐induced platelet aggregation, in either whole blood or platelet rich plasma, have not been demonstrated in diabetic patients without microvascular disease. In the present study platelet aggregation in the absence of exogenous agonists (‘spontaneous’ aggregation) was compared between 22 non‐diabetic subjects and 23 Type 1 diabetic patients with (n=12) and without (n=11) microvascular disease. ‘Spontaneous’ aggregation was determined by measuring the percentage fall in single platelet number in aliquots of whole blood shaken for 60 min. Diabetic patients without microvascular disease had fewer single platelets remaining (greater aggregation) than non‐diabetic subjects at all time‐points (69.7 ± 6.6 vs 82.3 ± 7.3 % at 60 min p<0.001), but more platelets remaining than in diabetic patients with microvascular disease at all time‐points (69.7 ± 6.6 vs 61.0 ± 7.8 % at 60 min p<0.02). No significant correlations were observed between platelet aggregation and plasma glucose, blood cell counts, or glycated haemoglobin levels. The study suggests that platelet abnormalities antedate the appearance of microvascular disease in diabetic patients.
Pulmonary Gas Exchange and Oxygen Uptake During Exercise in Patients with Type 1 Diabetes Mellitus
Authors: Wanke Th. , Formanek D. , Auinger M. , Zwick H. , Irsigler K.
Published: July 2009

In order to investigate pulmonary gas exchange and cardiopulmonary performance in Type 1 diabetes, 36 patients underwent a progressive incremental exercise test on a cycle ergometer. Cardiopulmonary variables were measured, and arterial blood gases determined on samples obtained from an indwelling catheter in the radial artery. The results were compared with those from 40 control subjects. In the patients, the maximum power (Wmax) and maximum oxygen uptake (VO2max) were lower than in the control subjects (Wmax 186 ± 52 (± SD) vs 233 ± 48 W, p< 0.05; VO2max 2.56 ± 0.71 vs 3.17 + 0.77 I min−1, p < 0.05). At comparable levels of power output, however, no significant abnormality was observed in the difference between alveolar and arterial oxygen pressure (P(A‐a)O2), and the ratio of physiological dead space to tidal volume (VD/VT ratio). These data indicate that in Type 1 diabetic patients, despite their reduced maximum oxygen uptake, gas transfer during exercise is not limited and thus does not contribute to the impairment of exercise capacity.
Skin Epidermal Thickness and Vascular Density in Type 1 Diabetes
Authors: Malik R. A. , Metcalfe J. , Sharma A. K. , Day J. L. , Rayman G.
Published: July 2009

Epidermal skin thickness and vascular density were assessed in skin biopsies obtained from the dorsum of the foot in 28 Type 1 diabetic patients and 17 normal control subjects, matched for age. Epidermal skin thickness did not differ significantly between control subjects (74 ± 4 (± SE) μ m) and diabetic patients (78 ± 4 μm). It was not related to the duration of diabetes and presence of complications. Neither small (capillary) nor large (arteriole/venule) vessel densities differed significantly between control subjects (59 ± 6 mm−2 and 19 ± 2 mm−2) and diabetic patients (65 ± 4 mm−2 and 22 ± 3 mm−2). Vessel densities were unrelated to the duration of diabetes and presence of complications.
Management of Diabetes in Surgery: A Survey of Current Practice by Anaesthetists
Authors: Clark J. D. A. , Currie J. , Hartog M.
Published: July 2009

A questionnaire survey of anaesthetists, based at the three main hospitals in Bristol, was undertaken to determine what methods are currently being used by anaesthetists to manage diabetes in patients for surgery. Replies were received from 56 of the 90 anaesthetists (62 %). Surgical procedures were defined as minor, moderate, and major. Two areas were identified where considerable differences in management between anaesthetists occurred, namely insulin‐treated patients requiring minor surgery, and non‐insulin‐treated patients requiring moderate surgery. In addition, no consensus view was apparent for the preferred intra‐operative blood glucose range or for the threshold blood glucose level at which to postpone an operation. It was apparent that anaesthetists preferred to administer intravenous insulin by a syringe pump rather than by a drip bag containing insulin, potassium, and glucose, particularly if more severe metabolic upset was anticipated. No difference in management was apparent between different hospital grades or between the three hospitals.
Clinical and Laboratory Features of Type 1 Diabetic Children at the Time of Diagnosis
Authors: Lévy‐Marchal C. , Papoz L. , de Beaufort C. , Doutreix J. , Froment V. , Voirin J. , Czernichow P.
Published: July 2009

The French incidence study has registered all new cases of Type 1 diabetic children under 20 years of age, from a population of 2.32 million, in an exhaustive and prospective manner. Three hundred and forty cases were identified between 1 January 1988 and 31 December 1989, yielding a mean annual incidence rate 7.3 per 105. The lowest rate was observed in the youngest age group (0–4 yr: 4.1 per 105) and the highest around pubertal development (10–14 yr: 11.5 per 105). Details of the previous personal and family history, and the clinical and biological pictures of the disease at diagnosis were recorded. Almost 8 per cent of the children had a first‐degree relative with Type 1 diabetes. Polyuria, weight loss, fatigue and abdominal pain were the most frequently reported symptoms, which were of median duration 4.4 months. Mean weight loss before diagnosis was 9.4 ± 6.8 (±SD) % of body weight and was not significantly related to age. Ketonuria was detected in 83.8 per cent and acidosis (total CO2 ≤ 18 mmol I−1, if measured) in 48 per cent of the cases. Ketonuria and acidosis were significantly more frequent in the younger age group than in the rest of the group (p < 0.001).
A Case of Nephrotic Syndrome and Renal Dysfunction in a Pregnant Woman with Diabetes Mellitus
Authors: Hironaka K. , Makino H. , Kumagai I. , Haramoto T. , Yamasaki Y. , Shikata K. , Takahashi M. , Nishii M. , Ota Z.
Published: July 2009

A 29‐year‐old diabetic woman who developed severe anaemia, nephrotic syndrome, and hypertension before the 28th week of gestation, had residual evidence of toxaemia and renal dysfunction more than 1 month following delivery. The histopathological findings of renal biopsy specimens were considered most consistent with toxaemia of pregnancy complicated by diabetic glomerulosclerosis. We consider that rapid acceleration of renal dysfunction may have been induced by: (1) poor control of diabetes before pregnancy; (2) glomerular hyperfiltration of the remnant nephrons throughout pregnancy; (3) hypercoagulopathy associated with pregnancy; (4) appearance of hypertension following these three conditions.
Aetiology of Diabetic Foot Ulceration: A Role for the Microcirculation?
Authors: Flynn M.D. , Tooke J.E.
Published: July 2009

Neuropathy, mechanical stress, and macrovascular disease are involved in the pathogenesis of diabetic foot ulceration. Implicit in the development of gangrene and ulceration is the recognition that these factors interact with the microcirculation, resulting in the failure of skin capillary flow to meet nutritive requirements. There is little evidence to associate structural microangiopathy with foot microcirculatory failure. Significant functional abnormalities of the microcirculation have been defined. In accord with the haemodynamic hypothesis early hyperaemia and capillary hypertension promote more sinister late functional abnormalities with increasing duration of diabetes. These late functional abnormalities include loss of autoregulation and reduced hyperaemic responses which interact with loss of neurogenic flow regulation, disturbed endothelial function, and abnormal rheology to produce the familiar clinical picture of the diabetic foot. Ischaemia secondary to multi‐segment arterial disease induces additional abnormalities of microcirculatory function which are superimposed on the pre‐existing diabetic microvascular structural and functional microangiopathy.
Intranasal Administration of Insulin With Phospholipid as Absorption Enhancer: Pharmacokinetics in Normal Subjects
Authors: Drejer Kirsten , Vaag A. , Bech K. , Hansen P. , Sørensen A.R. , Mygind N.
Published: July 2009

The pharmacokinetics of intranasal insulin containing a medium‐chain phospholipid (didecanoyl‐L‐alpha‐phosphatidylcholine) as absorption enhancer, was studied in normal volunteers by measuring plasma glucose, insulin, C‐peptide, and glucagon. Eleven fasting subjects received 4 U insulin intravenously, 6 U subcutaneously, or three doses intranasally (approximately 0.3 U kg−1, 0.6 U kg−1, 0.8 U kg−1) in random order on five separate days. Intranasal insulin was absorbed in a dose‐dependent manner with a mean plasma insulin peak 23 ± 7 (± SE) min after administration. Mean plasma glucose nadir was seen after 44 ± 6 min, 20 min later than following intravenous injection. Furthermore, intranasal administration of insulin resulted in a faster time‐course of absorption than subcutaneous injection, with significantly reduced intersubject variation (p < 0.001). Bioavailability for the nasal formulation was 8.3% relative to an intravenous bolus injection when plasma insulin was corrected for endogenous insulin production estimated by C‐peptide. A dose‐dependent suppression of C‐peptide and stimulation of glucagon secretion occurred after intranasal administration of insulin. Nasal irritation from spraying was absent or slight.
The Effects of Dexfenfluramine on Blood Glucose Control in Patients with Type 2 Diabetes
Authors: Willey Karen A. , Molyneaux L. M. , Overland J. E. , Yue D. K.
Published: July 2009

Dexfenfluramine has been shown to promote weight loss in overweight people. The present double‐blind study was designed to test whether the addition of dexfenfluramine to conventional oral hypoglycaemic treatment would promote weight loss and improve blood glucose control in overweight patients with Type 2 diabetes. The 34 patients studied were randomly assigned to dexfenfluramine or placebo therapy which was added for 12 weeks to their existing treatment regimens of metformin with or without a sulphonylurea. Dexfenfluramine treatment was associated with a significant reduction in weight (98.7 ± 5.0 (± SE) vs 94.9 ± 5.2 kg; p <0.001), BMI (35.0 ± 1.2 vs 33.6 ± 1.9 kg m−2; p < 0.001), HbA1c (7.5 ± 0.3 vs 6.3 ± 0.2%; p < 0.001), fructosamine (313.9 ± 17.6 vs 274.3 ± 10.4 μmol I−1; p < 0.01), systolic (137 ± 5 vs 128 ± 6 mmHg; p < 0.05), and diastolic blood pressure (85 ± 2 vs 73 ± 3 mmHg; p < 0.001). At the end of the study period, the dexfenfluramine treated group had a significantly lower HbA1c (6.3 ± 0.2 vs 7.2 ± 0.4; p <0.05), fructosamine level (274.3 ± 10.4 vs 313.3 ± 16.1 μmol I−1; p < 0.05) and diastolic blood pressure (73 ± 3 vs 81 ± 3 mmHg; p < 0.03) when compared with the placebo group. In those patients treated with dexfenfluramine, the reduction in HbA1c and blood pressure did not correlate with the decrease in BMI (r = 0.44 and 0.12, respectively). Dexfenfluramine is a valuable adjunct to the treatment of the overweight patient with Type 2 diabetes.
Body Fat and Overweight Among Children and Adolescents with Diabetes Mellitus
Authors: Gregory J.W. , Wilson A.C. , Greene S.A.
Published: July 2009

Body composition was assessed in 68 children and adolescents with diabetes mellitus. Body fat was measured by skinfold thickness and the results were compared with those obtained by bioelectrical impedance methods (r = 0.76, p < 0.001). Percentage body fat from skinfold thickness estimations was 12–38%. Girls appeared to be most at risk of obesity during puberty with mean body fat 31%, significantly greater than in prepubertal girls (22%, p = 0.001) and pubertal boys (21%, p < 0.001). Body fat increased progressively through puberty in girls, with those in late puberty (stages 4 and 5) having significantly more percentage body fat than those in earlier puberty (stages 2 and 3, p < 0.001). Those in late puberty also received significantly more insulin per kilogram body weight (p = 0.05) and had higher HbA1 levels (p < 0.05) than prepubertal girls.
Discrimination Between Painful and Painless Diabetic Neuropathy Based on Testing of Large Somatic Nerve and Sympathetic Nerve Function
Authors: Tsigos C. , White A. , Young R.J.
Published: July 2009

The syndromes of painful diabetic neuropathy and painless foot ulceration are distinct clinical entities. To investigate whether there is a pattern of nerve fibre involvement that could clearly discriminate between them, we have studied three groups of diabetic patients, 19 with painful neuropathy, 14 with painless foot ulceration, and 19 with no clinical neuropathy. Large somatic nerve fibre function was assessed by nerve conduction studies and vibration thresholds, small somatic nerve function by cooling and warming thresholds, the parasympathetic system by heart‐rate dependent cardiac autonomic reflexes, and the sympathetic system by postural drop in blood pressure and plasma noradrenaline (supine and erect). Normal ranges were obtained from 25 age‐matched healthy subjects. Painful neuropathy was characterized by uniform dysfunction of small somatic fibres and preserved sympathetic nerve activity (plasma noradrenaline) with a wide range of large somatic fibre and autonomic reflex abnormalities. By contrast, in painless foot ulceration there was universal severe dysfunction of all nerve fibre populations. Discriminant analysis identified peroneal motor conduction velocity as the best single variable for distinguishing between painful and painless neuropathy (81% of cases). A combination of peroneal motor conduction velocity with vibration threshold and plasma noradrenaline discriminated completely between the two clinical syndromes. These findings suggest that the key differences between painful and painless diabetic neuropathy are in large somatic and sympathetic fibre function.
Hospital In‐patient Statistics Underestimate the Morbidity Associated with Diabetes Mellitus
Authors: Leslie P.J. , Patrick A.W. , Hepburn D.A. , Scougal I.J. , Frier B.M.
Published: July 2009

Hospital in‐patient statistics are an important outcome measurement in the assessment of the morbidity associated with diabetes mellitus. A prospective study of 157 consecutive admissions over a 28‐day period compared diagnoses obtained from the clinical records with the ICD9 coding of the same admissions recorded at the Information and Statistics Division of the Scottish Health Service. Sixty‐one percent of all discharge summaries omitted the diagnosis of diabetes. Even when admission was principally related to diabetes complications, 47% of medical and 88% of surgical discharge summaries omitted diabetes as a diagnostic category. ICD9 coding underestimated the percentage of admissions accounted for by diabetic patients by 100% (2.8 vs 5.6%) and as a result underestimated bed occupancy by over 200% (4.3 vs 13.7%), and is thus failing to fulfil its potential as a demographic and epidemiological record of resource use by disease classification.
Oral Disorders Associated with Diabetes Mellitus
Authors: Lamey P‐J. , Darwazeh A.M.G. , Frier B.M.
Published: July 2009

The protean manifestations of diabetes include various associated oral disorders such as sialosis, xerostomia, impairment of taste, and localized infections of which oral candidosis is the most commonly observed. The association of specific oral diseases and diabetes is of importance both in the detection of undiagnosed diabetes and in the elucidation of the pathogenesis of various oro‐facial diseases. The clinical features and possible causes of oral disorders recognized to be associated with diabetes are reviewed with emphasis on good oral hygiene in the diabetic patient.
Recent Trends in Diabetes Mortality in England and Wales
Authors: Stephenson J. , Swerdlow A.J. , Devis T. , Fuller J.H.
Published: July 2009

Trends in diabetes‐related mortality in England and Wales between 1975–6 and 1985–6, and regional and ethnic differences in diabetes‐related mortality in 1985–6, have been examined. Data from death certificates mentioning diabetes in 1975–6 were compared with those for 1985–6 for different age groups. Data for 1985–6 were also analysed for different regions of England and Wales, and for country of birth. Between 1975–6 and 1985–6, the age‐standardized rate of mentioning diabetes rose by 2.7% (95% confidence interval 1.4%, 4.1%) in men of all ages, and fell by 11.7% (10.6, 12.8) in women of all ages. By contrast, the rate of mentioning diabetes in those below 45 years fell by 30.7% (23.0, 37.7) in men and by 26.7% (16.5, 35.6) in women. Deaths in which the underlying cause was ischaemic heart disease (IHD), and where diabetes was also mentioned on the death certificate, rose by 14.4% (11.5, 16.8) in men and did not change significantly in women of all ages, but fell by 18.4% (‐35.1, +2.6) in men, and 23.5% (‐49.1, +15.2) in women below age 45. This was less favourable than the trend in the general population, where IHD mortality fell by 9.7% in men and 8.3% in women of all ages, and by 31.1% (28.6, 33.5) in men and 40.5% (35.0, 45.5) in women under 45 years. The age‐standardized rate of mentioning diabetes in 1985–6 was 2.6 (2.4, 2.9) times higher in men and 2.5 (2.3, 2.8) times higher in women of all ages born in Africa or the Caribbean, compared with those born in the UK. The corresponding ratios for men and women born in the Indian subcontinent were 3.0 (2.8, 3.2) and 2.7 (2.5, 2.9). The ratios were also raised in persons below 45 years born in Africa or the Caribbean (1.6 for men plus women) or in the Indian subcontinent (1.6), but the increase was not significant. In conclusion, the reduction between 1975–6 and 1985–6 in the rate of mentioning diabetes in men and women dying before the age of 45 is substantial and encouraging, since other evidence suggests that the incidence of insulin‐dependent diabetes in England and Wales has increased over the past few decades. Trends in ischaemic heart disease mortality in association with diabetes are less optimistic.