Driving and diabetes: a summary of the current medical and legal position based upon a recent heavy goods vehicle (HGV) case.
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Biomedical subjects
Publications and source records attributed to C S Cockram.
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Disturbance of vision commonly accompanies hypoglycaemia. This study was designed to investigate the nature of the visual disturbance, the blood glucose threshold at which the disturbance occurred and the physiological basis. Measurements were made of the corrected visual acuity, colour vision (100 Hue test), visual evoked potentials (VEP), electroencephalography (EEG) frequency analysis and psychometry (digit recall) during stepwise induction of controlled hypoglycaemia produced by an intravenous insulin infusion. Six male volunteers and five insulin-dependent diabetic subjects were studied. During hypoglycaemia corrected visual acuity was unchanged. Colour vision was significantly impaired. Baseline VEP were normal in both groups but significantly prolonged during hypoglycaemia (mean increment 10.8 ms) and increased by greater than 5 ms in nine out of 11 subjects. Quantitative EEG analysis demonstrated slowing with a power density spectral shift from fast alpha to slow alpha, theta and delta which correlated with VEP latency and amplitude changes. The findings have clinical implications. A deterioration in colour vision is likely to impair the ability to read reagent strips by eye. VEP measurements in diabetic patients are likely to be misleading if hypoglycaemia is present; EEG changes are a sensitive index of cortical dysfunction during hypoglycaemia and provide a theoretical basis for developing a portable device to detect early hypoglycaemia.
The tyrosine residues at positions 14 and 19 of the insulin A chain are of both theoretical and practical interest. In order to clarify their roles in insulin function we have studied the biological properties of the two chemically modified insulins in which phenylalanine replaces tyrosine at these sites. In comparison to native bovine insulin the lipogenesis potency (in rat adipocytes) of pheA19-insulin was 33% and of pheA14-insulin was 84%. Metabolic clearance rates (MCR) over a range of plasma concentrations were also reduced compared to native insulin both with pheA19-insulin and pheA14-insulin. Plasma half-disappearance times were 4.6 min for insulin, 5.1 min for pheA14-insulin and 7.3 min for pheA19-insulin. However, as a result of these differences in metabolism, the in vivo hypoglycaemic activity of the modified insulins was not reduced. Both modified insulins conform to the general relationship between lipogenesis potency and MCR. These results confirm the importance of the A19 tyrosine to the activity of insulin and show that manipulation at the A14 position can also influence activity even though this residue is not thought to be directly involved in receptor binding.
To compare the metabolic characteristics and degradation of insulin tracers labeled unselectively, selectively at the A14 position (A14-monoiodoinsulin), and selectively at the B1 position (B1-monoiodoinsulin), we have followed the time course of disappearance of intact (immunoprecipitable [IP] and trichloroacetic acid [TCA] precipitable) iodoinsulin after bolus injection into greyhounds. We have used noncompartmental analysis to determine metabolic clearance rate (MCR) and apparent distribution space (DS). We have also measured the appearance of non-IP- and non-TCA-precipitable fragments, and have developed a mathematical model using compartmental analysis to explain the observed differences. B1-Monoiodoinsulin has a significantly higher MCR (16.3 ml/min/kg) than both A14-monoiodoinsulin (10.6 ml/min/kg) and unfractionated tracers (7.6 ml/min/kg) as determined by immunoprecipitation, and reaches the values observed for native insulin in greyhounds. MCR values obtained by TCA precipitation are approximately one-half of those obtained by IP for all 3 tracers. The concentration of non-IP fragments is significantly lower with B1-monoiodoinsulin than with the other tracers. Compartmental analysis suggests this to be due to greater intracellular retention of the B1 moiety during the experimental period. We conclude that: (1) by the criterion of MCR, B1-monoiodoinsulin seems to behave more like native insulin than other preparations tested; (2) the reduced MCR of A14-monoiodoinsulin raises doubts about its validity as a tracer for insulin; (3) a high-molecular-weight product of insulin degradation, which includes both the B1 and the A14-A19 regions of the molecule, is released into the circulation; and (4) smaller fragments containing A14-A19 reappear in the circulation more rapidly than fragments containing B1.(ABSTRACT TRUNCATED AT 250 WORDS)
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The glomerular and tubular function of 7 patients with a spectrum of renal impairment was measured before, during and after 4-days' treatment with cefuroxime and gentamicin. Neither the mean plasma urea nor creatinine concentrations of the group increased after combined treatment, nor was the excretion of cefuroxime slowed. The ability to acidify and to concentrate the urine did not change. In only 1 patient did plasma creatinine increase and GFR fall. This patient had an unexpectedly high plasma gentamicin concentration and was taking frusemide. However, an eighth patient with acute renal failure caused by bacteraemic shock rapidly recovered renal function while being treated with cefuroxime and gentamicin for 15 days after large doses of frusemide intravenously. This limited study suggests that the useful combination of cefuroxime and gentamicin need not be denied to patients with reduced renal function, but emphasizes that the plasma gentamicin concentration must always be monitored.
A patient is described who simultaneously developed the yellow nail syndrome and nephrotic syndrome. Treatment of the nephrotic oedema coincided with return of normal nail growth.
BACKGROUND: To examine the lipid profile in Chinese type 2 diabetic patients and their relationship with anthropometric parameters, glycaemic control and cardiovascular mortality. METHODS: A consecutive cohort of 562 newly referred patients with type 2 diabetes to a hospital-based diabetes centre were examined in 1996. Subjects treated with lipid lowering drugs at the time of referral were excluded. A total of 517 subjects were followed up over a mean (+/-SD) period of 4.6 +/- 0.9 years. Glycated haemoglobin (HbA1c), fasting insulin and lipid profile and anthropometric parameters were documented at the time of recruitment. Cardiovascular mortality, mainly due to coronary heart disease and stroke, was ascertained using death registry and review of hospital case notes in 2001. RESULT: Of the 517 subjects (mean age of 54.0 +/- 14.0 years), 42.6% were men. In this cohort, 63.3% of subjects were either overweight (BMI > or = 23 kg/m2) or obese (BMI > or = 25 kg/m2) using Asian criteria. The mean (+/-SD) total cholesterol (TC), LDL-Cholesterol (LDL-C), HDL-Cholesterol (HDL-C) and geometric mean (x// antilog SD) of triglycerides (TG) were 5.6 +/- 1.3 mmol/L, 3.6 +/- 1.1 mmol/L, 1.3 +/- 0.3 mmol/L and 1.46x//1.90 mmol/L respectively. TC and LDL-C correlated positively with HbA1c, HDL-C negatively with BMI and WC (waist circumference), while TG positively with HbA1c, BMI, WC and HOMA (insulin resistance estimated using the homeostasis model assessment). During the 4.6 years follow-up period, there were 61 deaths giving a total mortality rate of 11.4%, of which 15 (25%) were because of cardiovascular events. Apart from age and disease duration, logarithm of TG was significantly associated with increased risk of cardiovascular mortality (p = 0.049, relative risk = 2.97, 95% CI 1.00-8.77). CONCLUSIONS: Chinese type 2 diabetic patients had a lower prevalence of obesity, lower TG and higher HDL-C than Caucasian patients. Despite the low incidence of cardiovascular death, TG, which was closely associated with obesity indexes, was significantly associated with cardiovascular death in these patients.
BACKGROUND: The aim of this study was to investigate the familiality and clustering of type 2 diabetes (T2DM) and metabolic syndrome (MES) predominantly in families with young-onset diabetes from the Hong Kong Family Diabetes Study. METHODS: One hundred and seventy-nine families (913 subjects) were ascertained through a diabetic proband. Anthropometry, glucose homeostasis, blood pressure and lipid levels were examined. Familial aggregation and inter-relationships of these traits were examined by recurrence risk ratio, heritability, genetic and environmental correlations. RESULTS: One hundred and forty families (78%) had at least one subject with early-onset T2DM (age-at-diagnosis </=40 years). MES was highly prevalent in probands (53%) and siblings (25%). Recurrence risk ratios in siblings were high for T2DM (4.3), hypertension (2.9) and central obesity (2.0). Body mass index, waist circumference, blood pressure, plasma insulin, triglyceride, HDL-cholesterol levels, insulin resistance and beta-cell function had high estimates of heritability (0.45-0.63). Bivariate quantitative analyses revealed differential contribution of genetic and environmental factors to the phenotypic correlation between metabolic trait pairs. Obesity indices showed the strongest phenotypic correlation with other traits, and were significantly influenced by genetic factors (genetic correlation = 0.29-0.60). CONCLUSION: There was significant familial aggregation of T2DM and related phenotypes including obesity, hypertension and dyslipidaemia. The clustering of metabolic traits is likely due to genetic effects, interacting with shared and unique lifestyle/environmental factors. The high familiality suggests that screening for MES is important, especially in families with young-onset diabetes, and that the families in HKFDS are valuable subjects for genetic studies of these metabolic diseases.
Microangiopathic complications are major causes of morbidity and mortality in diabetic patients. We studied 150 consecutive young Chinese diabetic subjects attending the Prince of Wales Hospital Diabetes Center on their presence of diabetic microangiopathic complications and the relationships with other risk factors. All patients with aged younger than 40 years and had an age of onset of disease at younger than 35 years. Their known duration of diabetes was 57.2 +/- 5.0 months. Of these 150 patients, 50 (33.3%) had microangiopathic complications, 34 (22.7%) had albuminuria, 11 (7. 3%) had peripheral neuropathy, and 21 (14%) had retinopathy. Using multiple logistic regression analysis, albuminuria was independently associated with body-mass index and systolic blood pressure, peripheral neuropathy was associated with fasting plasma glucose and lower high-density lipoprotein cholesterol, and retinopathy was associated with duration of disease and fasting plasma glucose. In conclusion, there were high percentages of microangiopathic complications, particularly albuminuria, in our young Chinese diabetic patients. Obesity, high blood pressure, and poor glycemic control are important for these complications.
The relationship between diabetes and Helicobacter pylori (HP) infection is controversial. In this study, we examined the possible relationship between HP infection and type 2 diabetes in Chinese subjects. Sixty-three Chinese type 2 diabetic patients (mean age +/- SD: 49.9 +/- 12.0 years; range: 17-76 years) were recruited irrespective of the duration of diabetes or type of therapy. Twenty-nine (46%) of them had upper gastrointestinal symptoms and the other 34 (54%) did not. Another 55 age- and sex-matched non-diabetic subjects (mean age +/- SD: 45.6 +/- 15.6 years, p=0.098; range 18-79 years) with dyspepsia indicated for upper endoscopy were recruited as a comparison group. Upper endoscopy was performed with antral mucosal biopsy specimens taken for rapid urease test (CLO test). HP infection was considered to be present if the rapid urease test was positive. The rates of HP infection of the diabetic and non-diabetic individuals were 50.8% and 56.4% respectively (p: NS). The rate of HP infection was similar between the 2 groups of diabetic patients with or without gastrointestinal symptoms (42.9% vs. 56.3%, p: NS). Using logistic regression analysis (forward stepwise) with age, sex, glycaemic control, duration of diabetes and upper gastrointestinal symptoms as independent variables to predict the risk of HP infection in diabetic patients, none of the parameters enter into the model. In conclusion, the rate of HP infection in Hong Kong Chinese subjects with type 2 diabetes is around 50%, which is similar to control subjects. No association was found between HP infection, glycaemic status, and duration of diabetes and upper gastrointestinal symptoms in these diabetic subjects.
Non-insulin-dependent diabetes mellitus of early onset has recently been described in Caucasians as a distinct syndrome with a characteristic pedigree suggestive of inheritance of genetic determinants from both parents. It is characterized by absence of islet cell antibodies and the severity of its clinical course. We report a Chinese family pedigree of three generations in which this form of diabetes has affected the third generation. Some members of this pedigree had severe complications at presentation in their twenties.
A double-blind, randomised study of the antihypertensive efficacy of perindopril and ketanserin in 44 elderly noninsulin-dependent diabetic patients aged > or = 60 years was conducted. Blood pressure, blood biochemical and haematological parameters, plasma vasoactive hormones, urinary volume, electrolytes and microalbumin were measured at baseline, after a 4-week placebo period, and at intervals during 8 weeks of treatment with active drug. Electrocardiogram and echocardiogram data were also obtained. Dosages of perindopril used were 2 mg once daily for 4 weeks doubling to 4 mg once daily if a target blood pressure of < or = 160/90 mm Hg was not reached. Dosages of ketanserin were 40 mg twice daily increasing to 80 mg twice daily. Both drugs caused a small but statistically insignificant reduction in blood pressure. Although the response rates (supine systolic blood pressure reduction of > 10 mm Hg) were 54% for perindopril and 45% for ketanserin, target blood pressure (supine blood pressure 160/90 mm Hg) was reached in only 21% of perindopril and 20% of ketanserin recipients. Plasma creatinine and 24-hour urine sodium excretion increased in patients receiving ketanserin therapy. Glycaemic indices and the lipid profile did not change in either group, except for a reduction in plasma triglycerides in the ketanserin group. No changes in urinary microalbumin, electrocardiogram, or echocardiographic cardiac parameters were observed. It is concluded that in the present study neither drug provoked a significant blood pressure lowering effect and that serum creatinine increased in the ketanserin group.
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Thyroid-stimulating hormone (TSH) secreting pituitary adenoma is a rare but important cause of thyrotoxicosis. It poses a challenge for both diagnosis and management. We report the case of a young Chinese man presenting with thyrotoxicosis, complicated by congestive heart failure, secondary to a TSH secreting pituitary adenoma. The case illustrates the importance of prompt diagnosis and allows discussion of both medical and surgical management, including the use of a long-acting somatostatin analogue.