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Biomedical subjects

B F Clarke

Publications and source records attributed to B F Clarke.

At least 37 records · Page 2Linked to original sources

Evaluation of oral cisapride and metoclopramide in diabetic autonomic neuropathy: an eight-week double-blind crossover study.

Nineteen diabetic patients with autonomic neuropathy were enrolled in a double-blind crossover study of cisapride, metoclopramide and placebo. Symptoms were evaluated from diary cards and from assessments undertaken at the end of each eight week treatment period. Measurements of oesophageal transit, gastric emptying and whole gut transit were made before treatment began and at the end of each treatment period. Three patients dropped out early in the study, and the results from 16 patients were analysed. The severity of autonomic neuropathy, judged from cardiovascular reflex tests, correlated with delayed oesophageal transit and prolonged gastric emptying, but abnormal oesophageal transit and gastric emptying were often unrelated to the presence of upper gastrointestinal symptoms. Neither cisapride nor metoclopramide had a statistically significant effect on oesophageal transit, gastric emptying or whole-gut transit, nor was any significant effect on symptoms identified, although a trend towards reduced nausea and vomiting with metoclopramide and reduced epigastric fullness and diarrhoea with cisapride was suggested. Upper gastrointestinal symptoms correlate poorly with objective abnormalities of gastrointestinal motor function in diabetes. In consequence, the symptomatic benefit to be expected from correction of these motor abnormalities remains uncertain.

Adult↗

Evidence against a role for prostaglandins in sustaining renal hyperfiltration in type 1 diabetes mellitus.

The acute effect of inhibition of prostaglandin synthesis with indomethacin 50 mg by mouth on renal haemodynamics has been examined in 8 male Type 1 diabetic patients with elevated glomerular filtration rate who were free of diabetic complications. Renal plasma flow and glomerular filtration rate were measured by constant infusion of para-amino hippurate and polyfructosan, the patients being studied at normoglycaemia. Urinary excretion of prostaglandin E2 fell from 885 +/- 160 to 345 +/- 115 pg min-1, and excretion of 6-keto-prostaglandin F1 alpha fell from 489 +/- 77 to 283 +/- 50 pg min-1. There was no change in renal plasma flow or glomerular filtration rate following indomethacin. The results do not support the hypothesis that increased renal prostaglandin synthesis is a cause of hyperfiltration in diabetes mellitus.

6-Ketoprostaglandin F1 alpha↗

A trial of the calcium antagonist felodipine in hypertensive type 2 diabetic patients.

Although calcium antagonists may impair insulin release in vitro, clinical studies have produced conflicting results. Felodipine is a highly selective dihydropyridine calcium antagonist effective in the treatment of hypertension. The efficacy of felodipine was assessed in a double-blind randomized placebo cross-over study of 21 Type 2 diabetic patients with primary hypertension, 13 men and 8 women, with an age of 61 (range 46-73) years. Thirteen were controlled on oral hypoglycaemic therapy and 8 on diet alone. Mean (SD) blood pressure (mmHg) was 176(20)/102(8) after a 2-4 week placebo run-in period, 169(21)/101(8) during the subsequent placebo period compared with 151(15)/88(9) after 4 weeks felodipine therapy (p less than 0.001). Nineteen patients required 5 mg twice daily and 2 patients 10 mg twice daily to achieve a target diastolic pressure of 95 mmHg. Side-effects seen with felodipine included ankle oedema, facial flushing, headache, and dizziness. During oral glucose tolerance tests performed after the felodipine and placebo phases, mean (SD) fasting blood glucose was 9.5(3.1) and 9.0(3.0) mmol l-1, respectively (NS), and the 90 min (peak) blood glucose was 19.1(4.8) and 18.1(4.8) mmol l-1, respectively (NS). Glycosylated haemoglobin and fructosamine concentrations likewise showed no significant changes.

Apolipoproteins↗

Relationship of skin thickness to duration of diabetes, glycemic control, and diabetic complications in male IDDM patients.

Skin thickness is primarily determined by collagen content and is increased in insulin-dependent diabetes mellitus (IDDM). We measured skin thickness in 66 IDDM patients aged 24-38 yr and investigated whether it correlated with long-term glycemic control and the presence of certain diabetic complications. With univariate analysis, skin thickness was increased and significantly related to duration of diabetes (P less than .001), previous glycemic control (P less than .001), retinopathy (P less than .001), cheiroarthropathy (P less than .001), and vibration-perception threshold (P less than .05). There was a negative correlation between forced expiratory volume at 1 s (P less than .05) and vital capacity (P less than .05) with duration of diabetes. Neither skin thickness nor ankle arteriomedial wall calcification correlated with abnormal autonomic function tests. When corrected for duration of diabetes, there was a weak correlation between skin thickness and glycemic control (P less than .05) but no correlation with retinopathy, cheiroarthropathy, and vibration-perception threshold. This study confirms that there are widespread connective tissue changes in diabetes mellitus, although the biochemistry needs further elucidation.

Adult↗

Blood group, secretor status and oral carriage of yeasts among patients with diabetes mellitus.

The inability to secrete the water-soluble glycoprotein form of the ABO blood group antigens is a genetic characteristic associated with susceptibility to superficial fungal infections and also insulin-dependent diabetes mellitus (IDDM). As oral carriage of Candida albicans in healthy adults is associated with non-secretion, we examined oral carriage of yeasts among 275 patients attending diabetic outpatient clinics, 137 with IDDM and 138 with non-insulin dependent diabetes mellitus (NIDDM) with reference to ABO blood group, secretor status and yeast species. Of the 166 yeast isolates, 109 (66.7%) were C. albicans, a lower proportion compared with 94% reported for healthy individuals. There was no association between ABO blood group and carriage. There was no increase in the proportion of non-secretor carriers of C. albicans among patients with IDDM; but among those with NIDDM, 44% of non-secretors were carriers compared with 21% who were non-carriers (p less than 0.01). The results are discussed in the context of host-parasite interactions influencing colonization.

ABO Blood-Group System↗

Neutrophil activation detected by increased neutrophil elastase activity in type 1 (insulin-dependent) diabetes mellitus.

Neutrophils have been implicated in the development of vascular disease, and increased plasma neutrophil elastase indicates increased neutrophil activation. The aim of this study was to determine whether neutrophil elastase levels, measured by radioimmunoassay, are altered in diabetes. One hundred Type 1 (insulin-dependent) diabetic patients and 35 comparably-aged control subjects were studied. There was no difference in the total white cell count, but the diabetic group had a higher neutrophil count (p less than 0.05). Plasma neutrophil elastase (p less than 0.001) and total neutrophil elastase (p less than 0.02) were increased in the diabetic group. The total neutrophil elastase levels reflected the neutrophil count, but plasma neutrophil elastase was independent of the number of neutrophils. The increased plasma neutrophil elastase level was not related to age, duration of diabetes, plasma glucose or HbA1. The results suggest an association between diabetes and neutrophil activation which may play a role in the development of vascular disease.

Adult↗

Plasma alkaline phosphatase isoenzymes in diabetes mellitus.

Alkaline phosphatase (ALP) isoenzymes were measured in type 1 diabetics, type 2 diabetics and in a non-diabetic control group. Within the diabetics and the control group, intestinal ALP activity was significantly higher in BO secretors than A secretors or ABO non-secretors. There was no difference in intestinal ALP activity between type 1 and type 2 diabetics but the diabetics had a significantly higher activity of this isoenzyme than the corresponding blood group/secretor status category of the control group. Liver ALP was significantly higher in the diabetics compared with the control group. Bone ALP showed no significant difference between the diabetics and the control group.

Adult↗

Somatosensory and visual evoked potentials in insulin-dependent diabetics with mild peripheral neuropathy.

Using somatosensory and visual evoked potential techniques we have looked for evidence of central neuropathy in a group of insulin-dependent diabetics with mild peripheral neuropathy. The N9, N13, and N20 components of the somatosensory evoked potential were significantly (P less than 0.001) delayed in the diabetic group compared with the control subjects. There was a small but non-significant increase in the interpeak N13-9 and N20-13 latencies in the diabetic group. The visual evoked potential (P100) showed a small but insignificant delay. The delay in cerebral evoked potentials was mostly attributable to peripheral neuropathic damage and no firm evidence was obtained in favour of central diabetic neuropathy.

Adult↗

Effectiveness of acarbose, an alpha-glucosidase inhibitor, in uncontrolled non-obese non-insulin dependent diabetes.

The effect of acarbose, an alpha-glucosidase inhibitor, on glycaemic control, was compared with placebo in a double-blind, randomised, group comparison study during 16 weeks in 20 non-obese non-insulin dependent diabetic patients in whom sulphonylurea treatment had been withdrawn. There was significant deterioration in glycaemic control as assessed by HbA1 following withdrawal of the sulphonylurea. There was no significant improvement in HbA1 between weeks 0 and 16 in either the acarbose (11.3% and 12.4% respectively) or the placebo group (10.6% and 12.2% respectively). In both the acarbose and placebo treated groups fasting glucose and insulin concentrations were unaltered. This study also suggests that acarbose was not an effective substitute for sulphonylureas in non-obese Type 2 diabetes uncontrolled by diet alone.

Acarbose↗

Hyperandrogenism, insulin resistance, acanthosis nigricans, and systemic lupus erythematosis associated with insulin receptor antibodies.

We report a young woman with systemic lupus erythematosis (SLE) who developed diabetes secondary to extreme insulin resistance, associated with severe hyperandrogenism and acanthosis nigricans. Her insulin resistance was found to be associated with high titers of insulin receptor antibodies. The hyperandrogenism has been favourably influenced by cyclical treatment with cyproterone acetate and ethinyl oestradiol, but the insulin resistance and acanthosis nigricans have remained unmodified after 15 months of follow up.

Acanthosis Nigricans↗

Increased urinary excretion of glycosaminoglycans in insulin-dependent diabetic patients with limited joint mobility.

Urinary excretion of glycosaminoglycans (GAG) was measured in 24-h specimens collected from 27 insulin-dependent male diabetic patients and 22 healthy males of similar ages. Excretion relative to creatinine was increased by 35% in the diabetic group as a whole (p less than 0.02). Twelve patients with limited joint mobility (cheiroarthropathy) formed a subgroup with high excretion (69% above controls), those without limited joint mobility being similar to controls. There was no correlation of retinopathy with GAG excretion.

Adult↗

The importance of the time interval between insulin injection and breakfast in determining postprandial glycaemic control--a comparison between human and porcine insulin.

This study assessed the effect of the time interval between insulin injection and breakfast in determining subsequent postprandial glycaemic control and also whether this differed between highly purified porcine insulin and human insulin (crb) in six diabetic patients (age range 24-36 years, duration of diabetes greater than 10 years) usually treated with twice daily Actrapid MC and Monotard MC and with stable insulin requirements and diabetic control. On separate mornings each patient was given, after an overnight fast, their usual dose of either Actrapid MC and Monotard MC or Humulin S and Humulin Zn injected 5, 20, or 40 min before a standard breakfast. The postprandial glycaemic profile was not significantly different at any of the three time intervals with Actrapid MC and Monotard MC. However, with the human insulin the profile was significantly better at the 40 min interval than at the 5 min interval (p less than 0.05) and this was also better than any of the profiles with the porcine insulin, there being a significant difference between the two types of insulin (p less than 0.05). These findings suggest that the time interval between insulin injection and breakfast may be more important with human insulin than with porcine insulin.

Adult↗

Reduced free radical activity detected by decreased diene conjugates in insulin-dependent diabetic patients.

Free radicals are unstable chemical species which react with and oxidize adjacent molecules, particularly polyunsaturated lipids. The diene-conjugated non-peroxide isomer of linoleic acid (PL-9,11-LA') has been identified as the main diene-conjugated compound in plasma, and is a probable marker of free radical activity. The aim of the current study was to determine whether the level of PL-9,11-LA', measured by HPLC, is altered in insulin-dependent diabetes, and to investigate whether any abnormality demonstrated correlated with microvascular disease in the form of retinopathy. There was no difference in the concentrations of linoleic acid between the diabetic and control groups (422(129) vs 402(81) (SD) mumol l-1). However, the concentration of PL-9,11-LA' was significantly reduced in the diabetic group compared with control group (15.6(6.7) vs 19.3(3.9) mumol l-1, p less than 0.01), with the molar ratio of PL-9,11-LA':linoleic acid x 100 similarly reduced (3.8(1.3) vs 5.0(1.6)%, p less than 0.005). This study does not support the concept that free radicals play a significant role in the development of diabetic vascular disease.

Adult↗

Are reduced lung volumes in IDDM due to defect in connective tissue?

Lung volumes were measured by spirometry and helium-dilution technique in 28 young adult men with insulin-dependent diabetes mellitus (IDDM) of long duration and compared with 16 age- and height-matched adult men without diabetes. Reduced values for forced expiratory volume at 1 s, vital capacity, functional residual capacity, total lung capacity, residual volume, and single-breath carbon monoxide transfer factor were found for the IDDM patients compared to the control subjects. The results are consistent with reduced lung volumes in IDDM patients and did not correlate with the presence or absence of mild cheiroarthropathy but may relate to duration of diabetes.

Adult↗

Chronic and remitting painful diabetic polyneuropathy. Correlations with clinical features and subsequent changes in neurophysiology.

Twenty-nine diabetic patients (19 men, 10 women) aged 19-71 yr with newly developed painful polyneuropathy were studied prospectively for 12-18 mo. Pain remitted completely in 16 patients within 12 mo, but continued in the other 13 patients. At presentation, no differences were found in the type or prevalence of symptoms or neurophysiological measurements (electrophysiology and cardiovascular autonomic function tests) between the patients whose pain remitted and those whose pain continued. Most electrophysiological measurements improved slightly in remitting patients but deteriorated slightly in those whose pain continued to reveal a significant difference (P less than .05) between the groups on final review. Similarly, abnormal autonomic nerve function improved slightly when pain remitted but worsened or persisted in patients whose pain continued, again revealing a significant difference between the groups (P less than .05) on final review. We also observed that pain remission usually occurred if the onset of symptoms shortly followed some sudden metabolic change (e.g., rapid improvement in glycemic control, ketoacidosis, anorexia nervosa) when the duration of diabetes was relatively short or when considerable weight loss preceded the onset of pain. We suggest that remitting and chronic painful diabetic polyneuropathy have distinctive clinical features at presentation and detectable neurophysiological differences during their symptomatic evolution.

Adult↗

Comparison of fructosamine with glycosylated hemoglobin and plasma proteins as measures of glycemic control.

The relative value of fructosamine as an alternative to glycosylated hemoglobin (HbA1) and other measures of glycemic control was assessed in 100 insulin-dependent (IDDM) and 104 non-insulin-dependent (NIDDM) diabetic patients. We measured HbA1 (by electrophoretic and affinity methods), plasma glucose, glycosylated plasma proteins, and fructosamine in blood taken at a single clinic visit. The values were compared both by correlation analysis and by considering whether the various indices of glycemic control placed the patients in the same clinical decision categories as they were in by the HbA1 (affinity) result. Fructosamine correlated moderately well with HbA1 (affinity; r = .8) and placed 71% of IDDM and 72% of NIDDM patients in the same clinical category of good, moderate, or poor control. Differences can probably be partly attributed to the different periods over which HbA1 and fructosamine reflect average glycemia and partly to imprecision.

Adolescent↗

Secretor state and complement levels (C3 and C4) in insulin dependent diabetes mellitus.

Lower levels of C3 and C4 components of the complement system have been reported for patients with insulin dependent diabetes mellitus (IDDM) but not among those with non-insulin dependent diabetes (NIDDM). We have found a significantly higher proportion of patients who are non-secretors of the ABO blood group antigens among patients with IDDM but not among those with NIDDM. As the gene that controls secretion of these antigens is in the same linkage group as that for the C3 complement component, we compared the levels of C3 and C4 of patients with IDDM by secretor state. The mean level of C3c for 45 non-secretors (75.2 IU/ml) was significantly lower than that found for 59 secretors (86.4 IU/ml) (p less than 0.025). The level of C4 among non-secretors (77.1 IU/ml) was also significantly lower than that of secretors (96.3 IU/ml) (p less than 0.025). The significance of these observations is discussed.

ABO Blood-Group System↗