bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Intensive Dietary Treatment on Insulin‐stimulated Skeletal Muscle Glycogen Synthase Activation and Insulin Secretion in Newly Presenting Type 2 Diabetic Patients
Authors: Johnson A.B. , Argyraki M. , Thow J.C. , Broughton D. , Jones I.R. , Taylor R.
Published: July 2009

Ten newly presenting, untreated, Europid Type 2 diabetic patients were studied before and after 8 weeks treatment with intensive diet alone. Nine normal control subjects were also studied. The degree of activation of skeletal muscle glycogen synthase (GS) was used as an intracellular marker of insulin action, prior to and during a 240‐min insulin infusion (100 mU kg−1 h−1). Fasting blood glucose decreased from 12.1 ± 0.9 (±SE) to 9.2 ± 0.8 mmol I−1 (p < 0.01), but there was no change in fasting insulin concentrations, 9.9 ± 2.3 vs 9.3 ± 2.1 mU I−1. Fractional GS activity did not increase in the Type 2 diabetic patients during the insulin infusion either at presentation (change −1.5 ± 1.9%) or after treatment (change +0.9 ± 1.8%), and was markedly decreased compared with the control subjects (change +14.5 ± 2.8%, both p < 0.001). Glucose requirement during the clamp was decreased in the Type 2 diabetic patients at presentation (2.2 ± 0.7 vs 7.3 ± 0.6 mg kg−1 min−1, p < 0.001), and despite improvement following dietary treatment to 3.3 ± 0.6 mg kg−1 min−1 (p < 0.01) remained lower than in the control subjects (p < 0.001). Fasting plasma non‐esterified fatty acid (NEFA) concentrations were elevated at presentation (p < 0.05), and failed to suppress normally during the insulin infusion. After treatment fasting NEFA concentrations decreased (p < 0.05) and suppressed normally (p < 0.05). Insulin secretion was assessed following an intravenous bolus of glucose (0.5 g kg−1) at euglycaemia before and after treatment. Both first (1 ± 1 vs 53 ± 9 mU I−1, p < 0.001) and second (148 ± 129 vs 781 ± 207 mU I−1 min, p < 0.02) phase responses were decreased compared with the control subjects. Following treatment the first phase response remained abnormal (2 ± 3 mU I−1), while the second phase response improved markedly (459 ± 206 mU I−1 min, p < 0.05), and was no longer significantly different to the control group. Thus the improved blood glucose control in the diet‐treated newly presenting Type 2 diabetic patients is likely to result from both increased insulin secretion and increased insulin action. The inability of insulin to activate skeletal muscle GS after treatment is likely to underlie the continued insulin insensitivity in these patients.
Respiratory Muscle Performance in Patients with Type 1 Diabetes
Authors: Heimer D. , Brami J. , Lieberman D. , Bark H.
Published: July 2009

Respiratory muscle strength and endurance were examined in 31 Type 1 diabetic patients and in age, sex, and weight matched control subjects. No significant difference in respiratory muscle strength was noted between the two groups. Maximal static inspiratory pressure was 92.3 ± 33.9 (± SD) and 99.5 ± 23.0% of the predicted values in the patient and control groups, respectively. Maximal static expiratory pressures were 75.1 ± 14.3 and 77.4 ± 14.0% of the predicted values in the patient and control groups, respectively. Respiratory muscle endurance was significantly lower in the diabetic patients 88.9 ± 20.7 vs 103.9 ± 15.8% predicted in the control group (p < 0.01). Total lung capacity, vital capacity, and maximal voluntary ventilation were also significantly lower in the diabetic group and correlated with the duration of diabetes.
The Epidemiology of Foot Lesions in Diabetic Patients Aged 15–50 Years
Authors: Borssén B. , Bergenheim T. , Lithner F.
Published: July 2009

All diabetic patients aged 15–50 years (n = 395) in the county of Umeå (population 118 500) were invited to have a standardized foot examination and 380 (96%) attended. Three‐quarters (78%) had Type 1 diabetes, 20% Type 2 diabetes, and 1% secondary diabetes. They were compared with 100 healthy control subjects. Both Type 1 and Type 2 diabetic patients had slight or moderate loss of forefoot arches more often than control subjects (57% and 60% vs 31%, p < 0.001). Callosities were not significantly more common in diabetic patients than in control subjects. Lesions observed on the lower legs and feet of the Type 1 and Type 2 diabetic patients were Melin's shin spots (33% and 39%), dry feet (33% and 29%), yellow toenails (27% and 31%), purpura (9% and 5%), ulcers (3% and 0%), necrobiosis (3% and 0%), and diabetic osteopathy (2% and 0%). Intermittent claudication was present in 1% and 3%, respectively. Three Type 1 diabetic patients had undergone below‐knee amputation. Two of the control subjects had Melin's shin spots. With the exception of necrobiosis which was only found in women with Type 1 diabetes and Melin's shin spots which were twice as common in diabetic men as women, whether Type 1 or Type 2, lesions were equally distributed between the sexes. Sensory thresholds for vibration, perception, and pain were significantly elevated in Type 1 diabetic patients with dry feet, fallen forefoot arches or hammer toes compared with those without. They were not increased in Type 2 diabetic patients or control subjects with these lesions. In conclusion, foot deformity and lesions of skin and nails are common in the feet of diabetic patients in this age group while macroangiopathy appears to be uncommon.
A Comparison Between the Diets of Pregnant Diabetic Women and Pregnant Non‐diabetic Women
Authors: Anderson A.S. , Lean M.E.J. , Pearson D.W.M. , Sutherland H.W.
Published: July 2009

In order to assess the effect of dietary advice for pregnant diabetic women, the habitual dietary intake of 8 pregnant diabetic women was assessed by 7‐day weighed food records. These results were compared with records from 8 non‐diabetic women, matched for age and gestation. Despite intense personalized dietetic advice to the diabetic women, there were no statistically significant differences in macro‐nutrient intake between the two groups. The diabetic women were encouraged to increase their carbohydrate intake slightly, but failed to achieve current British Diabetic Association dietary recommendations with respect to percent energy from carbohydrate (41 ± 5 (± SE)(range 29–47)%, BDA recommendation >50%) and percentage from fat 43 ± 6 (33–51)%, BDA recommendation <30%). Intake of bread and cereals was increased in the diabetic women, but increases in complex carbohydrates were insufficient to compensate for a reduced intake of high‐sugar foods. Intakes of energy from simple sugars were significantly lower (p < 0–05) in the diabetic group (12 ± 2 (5–20)%) than in the non‐diabetic group (21 ± 2 (12–28)%). There was no detectable difference in sources of fats in the diet between the two groups.
The Necessity of Achieving Good Laboratory Performance
Authors: Fraser C.G.
Published: July 2009

The results of clinical biochemistry tests are used in the diagnosis of diabetes mellitus by comparing them with reference values or agreed international criteria. Low analytical imprecision is required so that reference values are not unduly widened by analytical variability. Most laboratory test results are used in monitoring. Low analytical imprecision is required so that changes seen in sequential results reflect stability, amelioration or deterioration, not simply analytical variability. Analytical bias should be absent so that results are (1) comparable in individuals over time as methods evolve and instrumentation changes, (2) equivalent over locale since tests may be done in practitioners' surgeries, outpatient clinics, and laboratories, and (3) able to be interpreted against the fixed criteria. A plethora of strategies have been proposed to set numerical desirable standards of performance, these being termed analytical goals, including use of reference values, opinions of clinicians, state of the art, the views of experts, and data on biological variation. Use of data on within‐subject biological variation is currently considered the best approach. A generally applicable goal is that the total error should be less than one‐half of the within‐subject biological variation. Achievement of this adds about 10% through analytical variability to the true test variability. Analytical goals (CV, %) for glucose, fructosamine, urinary albumin, and haemoglobin A1 assays are 2.2, 2.1, 18, and 3.3%, respectively. These goals are targets worthy of attainment, not inflexible criteria of acceptance or rejection of methods.
Leucocyte Mobilization and Release of Neutrophil Elastase Following Acute Insulin‐induced Hypoglycaemia in Normal Humans
Authors: Collier A. , Patrick A.W. , Hepburn D.A. , Bell D. , Jackson M. , Dawes J. , Frier B.M.
Published: July 2009

Insulin‐induced hypoglycaemia in humans is associated with the rapid mobilization of leucocytes in peripheral blood. The aim of the present study was to determine whether neutrophil activation, manifested in plasma by neutrophil elastase concentration, occurs in response to insulin‐induced hypoglycaemia. Acute hypoglycaemia (mean blood glucose 1.3 ± 0.2 mmol I−1; mean ± SD) was induced with intravenous insulin in 15 normal human subjects, and provoked an increase in the neutrophil count from 3.4 (range 1.9‐6.5) to 10.7 (9.4–16.3) × 109 I−1 (p<0.001), and in the total leucocyte counts from 5.7 (4.1–8.1) to 12.8 (11.3–18.6) × 109 I−1 (p<0.001), with associated elevations in plasma neutrophil elastase concentration from 21 (12–34) to 29 (14–70) μ‐g I−1 (p<0.05), and in total neutrophil elastase concentration from 5.90 (3.13‐8.20) to 25.20 (23.00–52.00) mg I−1 (p<0.001). As neutrophil elastase is implicated in the development of vascular disease, this rise in response to hypoglycaemia may be of pathological importance in insulin‐treated diabetic patients.
Effects of α‐Glucosidase Inhibition and Viscous Fibre on Diabetic Control and Postprandial Gut Hormone Responses
Authors: Requejo F. , Uttenthal L. O. , Bloom S. R.
Published: July 2009

Twelve sulphonylurea‐treated Type 2 diabetic patients underwent treatment for 2‐week periods with the absorbable α‐glucosidase inhibitor BAY m1099 (50 mg thrice daily) and with guar granules (5 g thrice daily) separately and together in a sequence‐randomized double‐blind placebo‐controlled study. BAY m1099 and guar reduced the mean fasting plasma glucose from 10.0 ± 0.7 mmol I−1 to 8.7 ± 0.5 (p < 0.05) and 8.3 ± 0.7 mmol I−1 (p < 0.01), respectively. Both agents also lowered home‐monitored postprandial blood glucose, with BAY m1099 exerting the greater effect. Guar, but not BAY m1099, lowered serum cholesterol from 5.43 ± 0.52 to 5.29 ± 0.31 mmol I−1 (p < 0.05). BAY m1099 reduced the test breakfast plasma responses of glucose (p < 0.001) and gastric inhibitory polypeptide (GIP, p < 0.01) and increased those of peptide tyrosine‐tyrosine (p < 0.05) and motilin (p <0.01). Guar also reduced plasma glucose concentrations after a test breakfast (p < 0.05) and increased the response of neurotensin (p < 0.05). Combining treatments gave no further reduction of postprandial blood glucose concentration and was associated with an increased incidence and severity of gastrointestinal side‐effects.
Factors Related to the Electric Taste Threshold in Type 1 Diabetic Patients
Authors: Floch J. P. Le , Lièvre G. Le , Verroust J. , Philippon C. , Peynegre R. , Perlemuter L.
Published: July 2009

To specify the factors related to taste function in Type 1 diabetes mellitus, 50 diabetic out‐patients and 50 control subjects paired for age and sex were screened for taste disorders. None of them consumed significant amounts of alcohol, smoked, or had disease or took drugs capable of altering taste. Taste was studied with electrogustometry, retinopathy was detected by fluorescein angiography, nephropathy by measurement of albuminuria and microalbuminuria, peripheral neuropathy by electroneurography and electromyography, and autonomic neuropathy by cardiovascular function tests. The electrogustometric threshold was, on average, significantly higher in the diabetic group (133 ± 30 μA) than in the control group (29 ± 9 μA; p < 0.001). Electric hypogeusia (electrogustometric threshold > 100 μA) was found among 54% of the diabetic patients vs 2% of the control subjects (p < 0.001). In the diabetic group, the electrogustometric threshold was associated with complications of diabetes, especially with peripheral neuropathy (210 ± 24 vs 90 ± 22 μA; p < 0.001) and microalbuminuria (185 ± 25 vs 86 ± 21 μA; p < 0.01). It was correlated with age (r = 0.37; p < 0.01) and duration of diabetes (r = 0.52; p < 0.001) but not with HbA1c (r = −0.04). Using multivariate analysis, duration of diabetes and peripheral neuropathy had the strongest association with taste impairment. These results support previous findings, suggesting that taste impairment is a degenerative complication of diabetes mellitus.
Pathogenesis of Diabetic Neuropathy: the Role of the n‐6 Essential Fatty Acids and their Eicosanoid Derivatives
Authors: Jamal G.A.
Published: July 2009

A substantial disturbance of the metabolism of the n‐6 essential fatty acids exists in both human and experimental diabetes mellitus. Disturbances of the essential fatty acids and of the 1‐ and 2‐series prostaglandins derived from them create a variety of microvascular, haemorheological, and other abnormalities leading to reduced blood flow and neural hypoxia which will in turn produce a cycle of hypoxia. Disturbance of the n‐6 pathway may also result in functional and structural abnormalities of the axon, the myelin, and membrane‐bound proteins such as enzymes and receptors. Metabolic disturbances identified previously may have a synergistic effect in enhancing these pathogenetic changes.
Autonomic Dysfunction and Silent Myocardial Ischaemia on Exercise Testing in Diabetes Mellitus
Authors: Murray D.P. , O'Brien T. , Mulrooney R. , O'Sullivan D.J.
Published: July 2009

The incidence and mechanism of painless myocardial ischaemia on exercise testing in diabetic patients is not clear. Therefore, two studies were performed. Retrospectively, all exercise tests carried out in our hospital during the past 5 years were reviewed for silent ischaemia. Prospectively, diabetic patients with known or suspected coronary artery disease underwent autonomic function testing and a second exercise test. Of 1653 exercise tests reviewed, 247 were positive (ST depression > 0.1 mV). Of the 29 diabetic patients with positive tests 20 (69%) had painless ST depression, compared with 77 (35%) of the 218 non‐diabetic patients (p < 0.001). The diabetic patients with painful and painless ST depression were comparable for age, sex, therapy, but the 20 with no pain on exercise testing had a longer duration of diabetes and a higher incidence of microvascular complications than the 9 with pain (70 vs 22%, p < 0.05). In the prospective study, 12 of 30 diabetic patients with positive exercise tests had pain in association with ST depression and 18 had no pain. Six patients had mild and 12 severe autonomic neuropathy on formal testing. Twelve had no autonomic dysfunction. Eleven (92%) of 12 patients with severe neuropathy had painless ST depression, compared with 7 (39%) of 18 without severe neuropathy (p < 0.01). Thus, silent myocardial ischaemia on exercise testing is common among patients with diabetes mellitus and is associated with severe autonomic dysfunction.
Hypoglycaemia and Diabetes Mellitus Following Parenteral Pentamidine Mesylate Treatment in AIDS Patients
Authors: Perronne C. , Bricaire F. , Leport C. , Assan D. , Vilde J.L. , Assan R.
Published: July 2009

Of 18 AIDS patients withPneumocystis cariniipneumonia treated with pentamidine mesylate parenterally, four developed serious to severe hypoglycaemia, three hypoglycaemia followed by insulin‐requiring diabetes, and two others diabetes alone. Hypoglycaemia (blood glucose 2.1 ± 0.2 (±SE) mmol l−1) occurred 9 (2–22) days after starting treatment, and diabetes (initial blood glucose 30 ± 6 mmol l−1) after 60 (20–90) days. The other patients remained euglycaemic. The dysglycaemic patients (hypo‐ and hyper‐glycaemic) had a higher pentamidine dosage (p< 0.01), and higher serum creatinine levels at end of treatment (p< 0.001), consistent with drug accumulation and dose‐dependent toxicity.

Plasma C‐peptide levels were low in the diabetic patients, in the basal state (0.25–0.28 nmol l−1) and following stimulation by IV glucagon (0.35–0.40 nmol l−1), vs 0.80 ± 0.06 nmol l−1(basal) and 1.83 ± 0.16 nmol l−1(stimulated) in 23 healthy control subjects (mean ± SE). Islet cell or insulin antibodies were not detected. Serum amylase levels rose abnormally in the dysglycaemic group, and pancreatitis was proved in one, and suspected in another patient. None of 28 similar AIDS patients whoseP. cariniipneumonia was treated with cotrimoxazole showed blood glucose disturbance.
The Importance of Peripheral Pulses, Peripheral Oedema and Local Pain for the Outcome of Diabetic Foot Ulcers
Authors: Apelqvist J. , Larsson J. , Agardh C‐D.
Published: July 2009

In a prospective study, peripheral pulses, claudication, peripheral oedema, and rest pain were evaluated in 314 sequentially presenting diabetic patients with foot ulcers. In the ulcerated limb pedal pulses were found to be present in 44% of the patients, peripheral oedema in 38%, and rest pain in 19%. Twelve per cent had claudication. Presence of pedal pulses was more common in patients whose ulcers underwent primary healing (56%) than in those who healed after amputation (23%) or died (25%, p < 0.001). Eighty per cent of the patients with pedal pulses present underwent primary healing. However, 49% of patients with absence of pedal pulses also underwent primary healing and 12 patients developed gangrene despite presence of pedal pulses. Peripheral oedema was more common in patients who required amputation (58%) or died (55%) than in patients with primary healing (26%, p < 0.001). A tentative predisposing factor was identified in 95% of the patients, the most common factors being neuropathy, congestive heart failure, and previous deep venous thrombosis. Rest pain was more common in patients who required amputation (48%) or died (23%) than in those with primary healing (7%; p < 0.001). Only 50% of patients with gangrene had rest pain and of these patients, only one underwent primary healing. The presence of pedal pulses, oedema, and rest pain give valuable but imperfect information on the possible primary healing of foot ulcers in diabetic patients.
Identification of the Cohort of Type 1 Diabetes Presenting in Lombardy in 1983–84: a Validated Assessment
Authors: Calori G. , Gallus G. , Garancini P. , Repetto F. , Micossi P.
Published: July 2009

An incidence register for Type 1 diabetes was started in Lombardy in 1983–84 for people under 35 years of age. The main information source was the Regional Health Service record system, which provides anonymous reports on all patients discharged from public and private hospitals. Great care was taken to assure the quality of the data in the register. The clinical diagnosis was validated by examining the case notes. Completeness of the register was assessed using multiple independent sources of case ascertainment such as the list of the Youth Diabetics Association, the files of three hospital endocrinology centres, and the registry of conscripts rejected because of diabetes. The estimated age‐adjusted (world standard) annual incidence rate was 6.04 per 100 000 in the group 0–18 years and 5.96 per 100 000 in the age group 0–14 years. Females had peak incidence at 11 years of age, males had peak incidence 2 years later. These results confirm the low occurrence of Type 1 diabetes in northern Italy. A seasonal variation in onset of Type 1 diabetes was seen.
Different Absorption of Isophane (NPH) Insulin from Subcutaneous and Intramuscular Sites Suggests a Need to Reassess Recommended Insulin Injection Technique
Authors: Thow J.C. , Johnson A.B. , Fulcher G. , Home P.D.
Published: July 2009

The absorption of isophane (NPH) insulin from subcutaneous and intramuscular injection sites was measured in seven healthy volunteers using the euglycaemic clamp technique. Human Insulatard (Nordisk, Gentofte, Denmark) was administered in a dose of 0.25 U kg‐body‐weight−1 into the anterior compartment of the thigh. In random order injections were given either subcutaneously, via 12 mm needle at 45° to the skin into a skinfold, or intramuscularly by 25 mm needle perpendicularly to the skin. Insulin concentrations rose more rapidly after intramuscular injection than after subcutaneous injection, being significantly higher as early as 60 min after injection (19.7 ± 1.6 (± SE) vs 8.7 ± 1.4 mU l−1; p < 0.001). Thereafter insulin concentrations remained significantly higher for the remaining 360 min of study, reflected by a significantly greater area under the insulin concentration curve for the 420 min study (IM 8630 ± 1256 vs SC 4908 ± 465 mU l−1 min, p < 0.05). A significantly greater quantity of infused glucose was required to maintain euglycaemia after intramuscular injection than after subcutaneous injection (923 ± 256 vs 216 ± 71 mg kg−1 min, p < 0.05). These results demonstrate a striking difference in the pharmacokinetics of an isophane (NPH) insulin when injected into subcutaneous fat and muscle.
A Prospective Study of the Hazards of Multiple Use of Disposable Syringes and Needles in Intensified Insulin Therapy
Authors: Chlup R. , Marŝálek E. , Bruns W.
Published: July 2009

The aim of the present study was to evaluate the potential hazards of multiple use of disposable syringes and needles for insulin injections over a long period of time. A special syringe container (pen‐case) was developed to carry the syringe with insulin. In the microbial trial 24 patients, each injecting insulin for 1 week with one disposable needle, were studied for 201 patient‐weeks with 5829 injections. Cultures of 154 needles, 155 syringe rinses, 154 pen‐case rinses and the remains of insulin in 201 vials revealed no relevant contamination. In the clinical trial 100 diabetic patients were followed up for up to 7 years. Each syringe was reused for 1 to 12 weeks and each needle for 1 to 40 days (4 to 200 injections). Only sporadic redness not exceeding 4 mm2 was seen at sites of about 560 000 insulin injections. Thus, the repeated use of syringes and needles in one diabetic patient may be recommended as a convenient and safe approach in insulin administration.
Outward Bound, Diabetes and Motivation: Experiential Education in a Wilderness Setting
Authors: Herskowitz R. D.
Published: July 2009

Effective diabetes management requires the commitment to take charge of one's life, and the strength to face the daily challenges the illness presents on a long‐term basis. Outward Bound Programmes utilize challenging experiences in a wilderness setting to foster personal growth and responsibility, and to encourage the participants to reach beyond their limitations.

Six Outward Bound courses were taught, to a total of 56 students with Type 1 diabetes, 14 to 42 years old. With appropriate precautions, the fairly strenuous programme was conducted safely. A battery of psychosocial measures, administered to the initial pilot group of eight students before the course, and again 7 to 11 months after returning home, indicated a statistically significant improvement in problem scores on the Achenbach Youth Self‐Report Profile, and suggested modest improvements in diabetes adjustment, locus of control, and self‐esteem. Other course participants report having had an exhilarating experience, which helped to increase their self‐confidence and determination to take charge. A few have begun to break previous patterns of dysfunction. Many have acquired new insights into the causes of fluctuating blood sugars, and into the options at their disposal to optimize self‐care.
Scales to Measure Perceived Control Developed Specifically for People with Tablet‐treated Diabetes
Authors: Bradley C. , Lewis K. S. , Jennings A. M. , Ward J. D.
Published: July 2009

Scales to measure perceived control of tablet‐treated diabetes were adapted from a measure designed previously for insulin users. Development of the new scale is described and the psychometric properties are examined with responses from 187 tablet‐treated patients. The scales consist of seven subscales which may be combined to provide three composite scores indicating the extent to which respondents perceive Personal Control, Medical Control, and Situational Control over their diabetes. Relationships between subscales and composite scores were similar to those found previously for insulin users. Patients were significantly more likely (p < 0.001) to make attributions to Personal Control for their diabetes management rather than to Medical or Situational Control. As before, predictable biases were found in attributions to positive and negative outcomes. Correlations with medical and other psychological variables indicated that, as expected, stronger perceptions of Personal Control were associated with lower HbA, levels (r = −0.14; p < 0.05), lower percent ideal body weight (r = −0.24; p < 0.01), less Anxiety (r = −0.15; p < 0.05), greater Positive Well‐being (r = 0.21; p < 0.01) and greater Satisfaction with treatment (r = 0.34; p < 0.001). Complementary relationships were found with the measure of Situational Control. Wallston and Wallston's speculative Locus of Control typology was investigated using the new measures, and the findings provided support for the value of this approach.
Spectral Analysis of Spontaneous Heart Rate Variation in Diabetic Patients
Authors: Lanting P. , Faes Th.J.C. , Heimans J.J. , Ten Voorde B.J. , Nauta J.J.P. , Rompelman O.
Published: July 2009

In 28 diabetic patients and 62 control subjects spectral analysis of spontaneous beat‐to‐beat RR interval variations was performed. The spectral analysis focused on the dominant frequency of the mid‐frequency band (0.04–0.12 Hz) or baro‐oscillatory phenomenon (BOP). Compared with control subjects the dominant frequency of the BOP (BOP frequency) in the diabetic patients was lower (p < 0.001), and the difference increased with age. The shift of the BOP frequency was positively correlated with the reduced variation in heart rate during deep breathing (r = 0.80, p < 0.001) in the diabetic patients. These findings indicate that determination of the BOP frequency is a useful method for assessing cardiovascular autonomic function, supplementary to the known cardiovascular reflex tests. Measurement of the BOP frequency has the advantage that no active patient co‐operation is required.
Autonomic Denervation may be a Prerequisite of Diabetic Neuropathic Foot Ulceration
Authors: Ryder R.E.J. , Kennedy R.L. , Newrick P.G. , Wilson R.M. , Ward J.D. , Hardisty C.A.
Published: July 2009

Studies using visceral (cardiovascular) autonomic function testing have left doubt as to the importance of autonomic neuropathy in the development of diabetic neuropathic foot ulceration. A test for peripheral autonomic denervation has been developed (acetylcholine sweatspot test), dependent on intradermal acetylcholine causing secretion by innervated sweat glands, detected by starch/iodine discoloration. The response is photographed and quantified using a grid (normal score = 0 or 1; abnormal = 5 to 60). The sweatspot test was applied to the feet of 19 diabetic patients with a history of foot ulceration, 17 with neuropathic pain, 8 complaining of numbness, and to 15 diabetic control patients. The sweatspot test score of the foot ulcer patients (median 54) was very much greater than that of the other groups (pain group, 4, p < 0.005; numbness group, 2, p < 0.01; diabetic control group, 2, p < 0.0001). All the patients with neuropathic foot ulceration had peripheral autonomic denervation. The results suggest that autonomic denervation in the feet is always present in patients with diabetic neuropathic foot ulceration. Tests of peripheral autonomic denervation such as the acetylcholine sweatspot test may be useful to identify patients at risk of neuropathic foot ulceration.
Double‐blind Placebo‐controlled Study of the Effects of Bezafibrate on Blood Lipids, Lipoproteins, and Fibrinogen in Hyperlipidaemic Type 1 Diabetes Mellitus
Authors: Winocour P.H. , Durrington P.N. , Bhatnagar D. , Ishola M. , Arrol S. , Lalor B.C. , Anderson D.C.
Published: July 2009

The effects of bezafibrate 400 mg day−1 or placebo administered for 3 months, were compared in 36 patients with stable Type 1 diabetes and hypercholesterolaemia and/or hypertriglyceridaemia. Baseline characteristics of the 17 bezafibrate‐ and 19 placebo‐treated patients were comparable in most respects with the exception of concentrations of fasting serum triglycerides and blood glucose which were lower (NS) and plasma fibrinogen which were higher (p < 0.05), in those later treated with bezafibrate. Serum cholesterol concentrations decreased after 3 months bezafibrate treatment (from 7.1 (0.2) (SE) to 6.3 (0.3) mmol l−1, p < 0.05), predominantly due to a reduction in low density lipoprotein (LDL) cholesterol (from 4.8(0.3) to 4.2(0.3) mmol l−1, p < 0.05). Over the same period bezafibrate reduced serum triglycerides from 1.78 (95% CI 1.23‐2.57) to 1.26(1.02‐2.09) mmol l−1 (p < 0.05), and plasma fibrinogen from 4.1(0.2) to 2.9(0.2) g l−1, p < 0.001. Serum apolipoprotein B and apolipoprotein (a) showed no statistically significant changes. Overall there was no change in high density lipoprotein (HDL) cholesterol. However, in patients who were initially hypertriglyceridaemic there was significant increase in the cholesterol content of HDL and the HDL2‐cholesterol subfraction (both p < 0.05). After 3 months treatment with bezafibrate, fasting blood glucose levels were reduced from 8.5(1.1) to 6.4(0.7) mmol l−1, p < 0.05, without any change in glycosylated haemoglobin (9.2(0.4) to 9.1(0.5) %). At the end of the 3 months active treatment period, significant differences were recorded between the bezafibrate‐ and placebo‐treated groups for the following variables: fasting blood glucose (p < 0.001), very low density lipoprotein (VLDL) cholesterol, serum triglycerides, apolipoprotein B, HDL2‐and HDL3‐cholesterol and plasma fibrinogen (all p < 0.05). It is concluded that in Type 1 diabetic patients with hyperlipidaemia, bezafibrate is an effective serum lipoprotein modifying agent, and has a potentially important effect in reducing fibrinogen levels.
A Comparative Study on the Hormonal Responses to Insulin‐induced Hypoglycaemia Using Semisynthetic Human Insulin and Pork Insulin in Patients with Type 1 Diabetes Mellitus
Authors: Sjöbom N. Clausen , Lins P.‐E. , Adamson U. , Theodorsson E.
Published: July 2009

In order to enlighten the controversy on whether human and pork insulin result in different hormonal responses to insulin‐induced hypoglycaemia, eight C‐peptide negative, diabetic patients without measurable circulating insulin‐binding antibodies were exposed to insulin‐induced hypoglycaemia in random order with highly purified pork insulin (Actrapid) and semisynthetic human insulin (Actrapid Human). Hypoglycaemia was provoked by a constant rate IV infusion of insulin (0.034 U kg‐1 h‐1) for 3 h after which the blood glucose recovery was assessed for an additional period of 60 min. Both insulin preparations gave close to identical responses for glucose, glucagon, growth hormone, adrenaline, and somatostatin. The circulating noradrenaline levels were higher during the infusion of pork insulin which also yielded a more prominent response of pancreatic polypeptide and, after cessation of the insulin infusion, plasma cortisol was also higher following pork insulin. It is concluded that human and pork insulin induce close to identical responses of the important counter‐regulatory hormones during hypoglycaemia in Type 1 diabetic patients.
Vagus Nerve Morphology in Diabetic Gastropathy
Authors: Britland S.T. , Young R.J. , Sharma A.K. , Lee D. , Ah‐See A.K. , Clarke B.F.
Published: July 2009

Two patients were treated with gastroenterostomy and vagotomy for intractable vomiting due to diabetic gastropathy. A morphometric examination of nerve fibres and capillaries in their resected abdominal vagi was performed and the results were compared with findings from two diabetic and two non‐diabetic patients undergoing gastroenterostomy and vagotomy for duodenal ulceration. All four diabetic patients had pathological changes of a similar character: reduced myelinated fibre density, degeneration and regeneration of unmyelinated fibres, and capillary basement membrane thickening. Abnormalities were more pronounced in the two diabetic patients with gastropathy but intact and regenerating nerve fibres were still present. The findings support the view that vagal neuropathy could be a causal factor in diabetic gastropathy but imply that severe gastropathy with vomiting is not simply a consequence of autovagotomy. The morphological observations indicated that structural changes can occur in the autonomic nerves of diabetic patients who do not develop autonomic symptoms or have easily detectable abnormal autonomic physiology.
Long‐term Outcome After Photocoagulation for Proliferative Diabetic Retinopathy
Authors: Sullivan P. , Caldwell G. , Alexander N. , Kohner E.
Published: July 2009

One‐hundred and forty patients with 182 treated eyes were followed for up to 10 years after photocoagulation for proliferative diabetic retinopathy. Sixty‐eight patients were still alive and under review after 10 years. Mortality was 33% at 10 years and the survivors were younger when treated and had lower systolic and diastolic blood pressures, a lower urea and creatinine and a lower prevalence of proteinuria and ECG evidence of ischaemia at baseline. Sixty‐nine percent of all patients and 82% of those followed up for 10 years maintained good vision (6/12 or better) in their better eye at the last follow‐up. Visual deterioration occurred mostly in the first 2 years after treatment and risk factors for poor final vision were poor vision at baseline, severity of disc new vessels, and age at presentation. It is concluded that the short‐term beneficial effect of photocoagulation is maintained over long periods of follow‐up.
The Quality of Self‐monitoring of Blood Glucose
Authors: Colagiuri R. , Colagiuri S. , Jones S. , Moses R.G.
Published: July 2009

The accuracy of self‐monitoring of blood glucose (SBGM) was assessed by a quality control programme. Ninety diabetic patients who were routinely performing SBGM were supplied with a series of quality control solutions which they tested with their usual meter and reagent strip. The overall error rate (a result outside the range of the mean ± 3SD for each quality control solution) was 39% for users of the Ames system and 33% in Boehringer Mannheim system users. The clinical relevance of these errors was determined by examining the effect on the clinical decision which would have been based on the erroneous result, either in taking inappropriate action or in failing to take appropriate action. In 30% of all patients, 25% or more of the errors were of such a degree as to be clinically misleading. The most common error was an underestimation of the result, which gave the impression of better than actual blood glucose control. The main reason for these errors was the failure of patients to take sufficient care in following the manufacturers' instructions when performing the test. Clinically relevant erroneous results are common among patients performing SBGM.
Serum Lipids and Lipoproteins in Type 2 Diabetic Patients with Persistent Microalbuminuria
Authors: Seghieri G. , Alviggi L. , Caselli P. , de Giorgio L.A. , Breschi C. , Gironi A. , Niccolai M. , Bartolomei G.C.
Published: July 2009

To investigate whether persistent microalbuminuria is related to altered levels of both lipids and apolipoproteins in Type 2 diabetes mellitus serum total‐cholesterol, triglycerides, HDL‐cholesterol, LDL‐cholesterol, apolipoprotein A‐l, and apolipoprotein B were measured by standard methods in a group of Type 2 diabetic patients affected by persistent microalbuminuria (albumin excretion rate (AER) 20–200 μg min−1) as compared with a group of sex‐ and age‐matched non‐microalbuminuric patients (AER < 20 μg min−1). The groups were stratified according to a short (< 5 years) or a longer (> 5 years) duration of diagnosed diabetes. Microalbuminuria was not associated with significant changes of serum total‐cholesterol, triglycerides, HDL‐cholesterol, LDL‐cholesterol, and apolipoproteins in the group of patients with a duration of disease > 5 years, while microalbuminuric patients > 5 years from diagnosis (n = 11) had serum total‐cholesterol, triglycerides, LDL‐cholesterol, and apoprotein B higher than non‐microalbuminuric control patients (n = 26) (cholesterol 6.2 ± 0.9 vs 5.1 ±1.0 mmol I−1 (p = 0.003); triglycerides 2.1 ± 0.7 vs 1.7 ± 1.3 mmol I−1 (p = 0.03); LDL‐cholesterol 4.1 ± 0.8 vs 3.0 ± 0.7 mmol I−1 (p< .001); apo‐B 1.3 ± 0.3 vs 1.1 ± 0.3 g I−1 (p = 0.02). In these patients with shorter duration of diabetes many of the serum lipid measures correlated positively with AER.
Within‐clinic Glycosylated Haemoglobin Measurement
Authors: Rumley Mr.A.G. , Carlton G. , Small M.
Published: July 2009

The performance of the Diamat HPLC analyser (Bio Rad Instruments) was assessed, and the effect of this on‐site HbA1 assay on the therapeutic decisions made at the diabetic clinic evaluated. The intra‐assay CV for HbA1 at concentrations of 8.3 and 13.4 % was 3.8 and 0.4 %, respectively, with inter‐assay CV of 5.0 and 3.0 %. On a single day 82 HbA1 tests on consecutive patients were performed at the clinic. In 43 insulin‐treated patients and 79 non‐insulin‐treated diabetic patients the HbA1 result changed the management decision in 25 and 18 % of patients, respectively. The relationship between HbA1 and self blood glucose monitoring (SBGM) results in the previous 6‐week period were also evaluated. In 41 % of patients with insulin‐treated diabetes who produced SBGM diaries there was a discrepancy between categories of blood glucose control, all of these patients having better SBGM than HbA1 values. This study highlights the feasibility and value of a within‐clinic HbA1 assay for clinical decision‐making and its usefulness in identifying problems of agreement with self‐monitored tests.
A Randomized Cross‐over Study of the Effects of Proinsulin on Lipid Metabolism in Type 2 Diabetes
Authors: Winocour P.H. , Mallik T.H. , Ishola M. , Baker R.D. , Bhatnagar D. , Durrington P.N. , Anderson D.C.
Published: July 2009

The effects of human proinsulin and insulin on lipid metabolism in Type 2 diabetes were examined in a randomized cross‐over study in 15 patients. Blood glucose control was indistinguishable at the end of the two treatment periods, but fasting levels of triglycerides appeared somewhat lower after proinsulin (1.17(SE 0.16) vs 1.39(0.21) mmol I−1; p<0.07), and the maximal postprandial triglyceride response (2.19(0.25) vs 2.87(0.28) mmol I−1, p < 0.001) and triglyceride area under the curve (p < 0.01) were significantly reduced. In five hyperlipidaemic patients postprandial triglyceridaemia was reduced with proinsulin (2.89(0.60) vs 3.68(0.56); p < 0.001), but in addition fasting serum triglycerides (1.20(0.30) vs 1.96(0.30) mmol I−1, p < 0.04) and possibly VLDL‐cholesterol (0.49(0.15) vs 0.60(0.20) mmol I−1; p < 0.10) were lower and fasting LDL‐cholesterol levels higher (4.82(0.42) vs 3.92(0.57) mmol I−1, p < 0.03) after proinsulin therapy. Proinsulin appears to preferentially suppress the production of triglyceride‐rich lipoproteins in Type 2 diabetes, particularly postprandially, and may enhance their clearance and conversion to LDL, especially in hyperlipidaemic Type 2 diabetes
Changes in Carbohydrate Metabolism in Association With Glipizide Treatment of Type 2 Diabetes
Authors: Jeng C.‐Y. , Hollenbeck C.B. , Wu M.S. , Foley J.E. , Chen Y.‐D.I. , Reaven G.M.
Published: July 2009

Nineteen patients with Type 2 diabetes were treated with glipizide for 2.5–6 months, and measurements made of metabolic variables before and after glipizide treatment. For purposes of analysis, the glipizide associated decrease in fasting plasma glucose concentration was used to divide patients into ‘good’ responders (decrease of 4.0 mmol I−1 or more, n = 9) or ‘fair’ responders (decrease of 3.0 mmol I−1 or less, n = 10). Good responders had a significantly greater fall in their mean (± SE) hourly plasma glucose (6.3 ± 0.6 vs 2.7 ± 0.3 mmol I−1, p < 0.001) and NEFA (164 ± 40 vs 60 ± 37 μ‐mol I−1, p < 0.05) concentrations from 0800 to 1600 h in response to meals (0800 and 1200h) than did the fair responders. However, the increase in hourly plasma insulin concentration following glipizide treatment was the same in the good (323 ± 103 to 413 ± 124 pmol I−1) and fair (276 ± 42 to 345 ± 43 pmol I−1) responders. Good responders also had a significant increase in glucose metabolic clearance rate (MCR) following glipizide treatment during glucose clamp studies performed at plasma insulin concentrations of approximately 100 pmol I−1 (39 ± 4 to 53 ± 5 ml min−1 m−2, p < 0.02) and 600 pmol I−1 (109 ± 15 to 172 ± 32 ml min−1 m−2, p < 0.05), whereas in fair responders a significant improvement in glucose MCR was seen during the clamp performed at 100 pmol I−1 (46 ± 4 to 51 ± 3 ml min−1 m−2, p < 0.05), but not when insulin concentration was increased to 600 pmol I−1 (101 ± 13 to 105 ± 15 ml min−1 m−2, NS). Although glucose MCR increased in both glucose clamp studies in the good responders, the magnitude of the insulin‐induced increment in glucose uptake did not change significantly in response to glipizide therapy in this group. Glucose transport by adipocytes isolated from good responders (n = 4) was significantly higher (p < 0.001) after glipizide treatment in both the absence and presence of insulin, but the response to insulin did not change significantly with treatment. Basal hepatic glucose production also fell significantly (p < 0.05) in good responders (0.53 ± 0.06 to 0.29 ± 0.02 mmol min−1 m−2, n = 6), but not in fair responders (0.45 ± 0.04 to 0.42 ± 0.04 mmol min−1 m−2, n = 4, NS). Neither the ability of insulin to inhibit hepatic glucose production nor insulin binding to isolated adipocytes changed significantly following glipizide treatment. These results emphasize the variability in the blood glucose response to glipizide in patients with Type 2 diabetes, and demonstrate that those individuals with the best clinical response were characterized by a greater fall in circulating NEFA levels, a significant decrease in basal hepatic glucose production, and both in vivo and in vitro evidence of enhanced glucose uptake
Comparison of Basal and Prandial Insulin Therapy in Patients with Secondary Failure of Sulphonylurea Therapy
Authors: Paterson K.R. , Wilson M. , Kesson C.M. , Buchan M. , Roberts M. , Reith S.B.M. , Davidson E.
Published: July 2009

A group of 35 normal weight patients with secondary failure of sulphonylurea therapy (fasting plasma glucose >8.0 mmol I−1 on maximal dose of sulphonylurea) were randomly assigned to receive either a single injection of a basal insulin supplement (human ultralente insulin, n = 16) or three or four injections of a preprandial insulin supplement (human unmodified insulin, n = 19). Patients performed self‐monitoring of capillary blood glucose and adjusted their insulin doses in an effort to achieve fasting and preprandial capillary glucose concentrations of <7.0 mmol I−1. Blood glucose control after 16 weeks of insulin therapy was improved to a similar extent by both regimens (HbA1 basal insulin group 12.5 ± 1.2 (±SD) falling to 10.7 ±2.2%; preprandial group 12.0 ± 1.6 falling to 9.5 ± 1.6%). Preprandial insulin gave better control of daytime blood glucose levels but fasting plasma glucose did not differ between the two regimens (basal group 10.6 ± 3.6, preprandial group 11.1 ± 3.6 mmol I−1). Insulin dose was greater in the preprandial group (44.1 ± 17.9 U day−1) than in the basal group (26.7 ± 12.5 U day−1 (p < 0.005), but there was no difference in the frequency or severity of hypoglycaemia between the two treatments. Only the preprandial therapy group showed significant weight gain (2.7 ± 3.0 kg). While both regimens led to improvement of blood glucose control, these results suggest that neither basal nor preprandial insulin alone can achieve ideal blood glucose control through 24 h in patients with fairly severe failure of control on sulphonylurea therapy
Increased Proximal Tubular Reabsorption of Sodium in Childhood Diabetes Mellitus
Authors: O'Hagan M. , Howey J. , Greene S.A.
Published: July 2009

Type 1 diabetes mellitus is associated with an increase in total exchangeable body sodium. To delineate a site of possible altered sodium handling, proximal tubular sodium reabsorption (PTRNa) was measured in 30 diabetic children, age 12.0 (range 7–16) yr, duration of diabetes 4.5 (range 0.2–12) yr, and compared with 10 non‐diabetic children, age 10.0 (range 8.6–12.5) yr. PTRNa was calculated from the fractional clearance of lithium, which was determined from a single blood sample and a random untimed urine sample, taken between 0700 and 0830 h at home, fasting, before insulin therapy. PTRNa was significantly increased in the diabetic children compared with the non‐diabetic children (81.6(SE 1.0) vs 74.2(2.6)%, p = 0.014). There was no relationship of PTRNa with age, duration of diabetes, metabolic control (glycosylated haemoglobin, plasma and urinary glucose, plasma lactate), or urinary protein excretion (albumin, N‐acetyl‐β‐D‐glucosaminidase). Elevated sodium reabsorption in the proximal renal tubule may account for the high total exchangeable body sodium found in Type 1 diabetic patients