Blood-sugar and arterial disease.
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Biomedical subjects
Publications and source records attributed to H Keen.
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Of the threats to health and life that beset the person with diabetes, cardiovascular disease (CVD), particularly coronary heart disease (CHD) but also cerebrovascular and peripheral vascular disease, represent the heaviest burden. The relative risk for CVD is very high for Type 1 diabetes, but the absolute risk, in terms of numbers, is much higher for Type 2. In all societies, diabetes increases cardiovascular risk twofold or more, compared with the local non-diabetic population. Some of the evidence for this diabetes-related increase in cardiovascular risk is reviewed and its relationship to recognised cardiovascular risk factors considered. The explanation of the enhanced susceptibility to atherosclerotic disease in diabetes remains a matter of contention. How much can be explained by greater prevalence in diabetes of such risk factors as hypertension and dyslipidaemia? To what extent is the impact of a given level of risk factor magnified by a co-existing diabetic state? Is the increased cardiovascular morbidity and mortality secondary to risk factors specifically related to the diabetic state itself? Does the explanation lie in altered coagulability due to changes in platelet activation and aggregability, fibrinogen levels, Factor VII, von Willebrand factor or PAI-1, in the concentration or composition of plasma lipoproteins, in defective endothelial cell function or other metabolic abnormalities of the arterial wall? To what extent is cardiovascular risk related to the degree of hyperglycaemia, protein glycation, relative hyperinsulinaemia and insulin resistance? Data from recent epidemiological, intervention and laboratory investigations bearing on causation, management and prevention of CVD in diabetes are reviewed. Evidence for the impact of correction of glycaemia, dyslipidaemia and raised arterial pressure is considered and reasons are adduced for a broad and proactive therapeutic approach with early identification and vigorous correction of key risk factors.
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This paper offers a broad but selective account of the context of type 2 diabetes at the start of the new millennium. It outlines the major long-term threats to health and life of people with type 2 diabetes and indicates that, while their relative impacts may differ, the burden of the specific "microvascular" and the atherosclerotic "macrovascular" complications of diabetes weigh as heavily on people with type 2 as on those with type 1 diabetes. Correction of hyperglycemia still has a leading role among therapeutic objectives in type 2 diabetes, but the concept of the "defence in depth" and the crucial importance of control of arterial pressure and correction of dyslipidemia - the "bad companions" in diabetes - is stressed. Other defences against tissue and organ failure in diabetes are described, highlighting the importance of regular, systematic screening for risk factors and early manifestations of tissue damage. Broader organizational, social and economic factors in diabetes care are touched upon and the need for strong alliances of all concerned parties - care providers, managers, health politicians, and above all informed and motivated people with diabetes themselves - is underlined with reference to the World Health Organization/International Diabetes Federation St. Vincent Declaration Initiative in Europe and its recent 10-year anniversary "Istanbul Commitment" to full implementation of the Declaration.
A questionnaire was sent by the British Diabetic Association to hospital consultant physicians caring for diabetic patients in the UK to estimate the number of ethnic minority patients attending British Diabetic clinics, and the availability of special facilities for their care. Sixty-two clinics were estimated to have at least 50 Asian patients, and 25 had at least 200 Asian patients. For Afro-Caribbeans the corresponding figures were 33 and 14 clinics, respectively. Clinics serving a relatively high proportion of these patient groups were situated primarily in Greater London, the Midlands and the North West. Approximately 40% of clinics with over 50 Asians had no specifically adapted diet sheets, and 34% had no hospital interpreter service. Tapes, slides or video presentations were available in only eight clinics. There is an urgent need to improve the provision of special facilities to clinics with substantial numbers of ethnic minority patients.
A 6-month study of the effects on blood glucose control of computer-aided analysis of glucose self-monitoring results was performed. Eighteen clinically insulin-dependent patients were ranked in order of haemoglobin A1 and randomly allocated in consecutive pairs to either a conventional group, using diaries to record self-monitoring meter-read results, or a memory group using meters with inbuilt memories which were linked to a computer at each visit for the analysis of self-monitoring results. There was a significant decline in haemoglobin A1 (p less than 0.001) and fructosamine (p = 0.002) over the 6-month period in the whole population but there was no difference between the study groups. The absolute or percentage changes in haemoglobin A1 and fructosamine did not correlate significantly with any of the patient characteristics examined. The memory system was popular with the patients. At present no benefit in terms of blood glucose control from such systems has been demonstrated.
A general description of the multinational study under the auspices of the World Health Organization is presented. The purpose was to compare the prevalence of vascular disease in representative samples of diabetic subjects of different ethnic and cultural habitus. Standardized methods of investigation were devised. Fourteen centers participated, and the data collected so far indicate that the characteristics of the populations studied varied as to age composition, adiposity, cigarette smoking, treatment, age at diagnosis, and duration of diabetes. Thus, taking these factors into consideration and while awaiting completion of the data, conclusions must be drawn with reserve.
14 national groups have collaborated under WHO auspices to select, from local defined populations of individuals with clinical diabetes, groups of approximately 500 within the age range 35--55 yr stratified by age, sex, and known duration of diabetes. In each center, the selected patients were submitted to a standardized study protocol, which included systematic inquiry (WHO questionnaire) for the presence of symptoms of angina pectoris, history of myocardial infarction, presence of intermittent claudication, and cigarette smoking history. Examination included standard biometry, blood pressure measurement, 12-lead (centrally Minnesota coded) electrocardiography, and central laboratory measurement of serum cholesterol and creatine. Ophthalmoscopic and urinary examinations were also included. The prevalence of arterial disease symptoms and electrocardiographic abnormalities show very large variation between countries, the lowest rates generally being found in the Oriental samples and the highest in the European. "Risk factors" for arterial disease (blood pressure, serum cholesterol, and cigarette smoking) also vary widely between diabetic groups. Although data are not yet complete, these differences appear unlikely to explain the variation in the atherosclerotic morbidity observed. Diabetic women were at least as vulnerable to arterial disease as diabetic men. A high prevalence of nonspecific abnormalities of the repolarization phase of the ECG was found, even in groups where ischemic abnormalities were rare. The origin of these is uncertain; they may represent variable local changes or possibly diabetic cardiomyopathy. This preliminary report confirms and quantifies previous indications that the impact of atherosclerotic disease on persons with diabetes varies considerably between national groups, in broad terms, running parallel with the variations in prevalence in the populations in general and suggesting that cultural and/or ethnic factors are more important determinants of atherosclerosis in diabetic individuals than is the diabetic state per se.
A preliminary comparison and analysis of microvascular disease was performed in 14 stratified samples of diabetic subjects. Microvascular disease was assessed by estimating visual disabilities, by standardized examination of the optic fundus by direct ophthalmoscopy, by estimating proteinuria, and by measuring the serum creatinine concentration. Visual impairment by questionnaire positive varied considerably between centers, probably due to cultural differences in interpretation of the questions. Physician-assessed visual disability also yielded considerable differences in frequency; however, the frequency differences were unrelated to those observed for macrovascular disease. Retinopathy--the sum of all components--was related to duration of diabetes in each participating center. The apparent frequency of proteinuria varied considerably between centers. In general, the frequency of retinopathy was related to the level of systolic blood pressure, but there was no systematic association with cigarette smoking.
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Biosynthetic human insulin (BHI) produced by recombinant DNA technology was administered subcutaneously and intravenously at two dose levels to two groups, each consisting of six normal men. Responses were compared with those for purified pork insulin (PPI) given by the same routes at the same dose levels to the same two groups. The glycemic response to the insulins was similar with a suggestion (seen both with intravenous and subcutaneous administration) that the glycemic depression with BHI was slightly greater at low dose and less at high dose. No significant difference between insulin types was found in the depression of non-esterified fatty acid (NEFA) concentrations, although significant differences between types with low-dose subcutaneous injection emerged during the later phases of the experiment. After termination of high-rate infusion with both insulins, NEFA concentrations rose more rapidly with some overshoot, suggesting that the rate and depth of blood glucose fall in these experiments might have triggered a brisker counterregulatory response. The small differences found between human and pork insulins, although in some cases significant, are unlikely to be of clinical importance.
Ninety-four diabetic patients established on treatment with pork (N = 47) or beef insulin (N = 47) took part in a double-blind crossover trial in which 6-wk treatment periods of their animal insulin were compared with similar periods on human insulin (recombinant DNA). Six patients withdrew during the trial--in three cases for hypoglycemia while taking human insulin. In patients initially treated with beef insulin there was no significant change in the mean blood glucose, the 'M' index, the total daily insulin dose, or the frequency of hypoglycemic attacks after the change to human insulin. Home blood glucose sample values were greater before the morning and evening insulin injection on human insulin (morning: 12.8 mmol/L [beef] versus 14.2 mmol/L [human insulin] [P less than 0.05]; evening: 10.0 mmol/L versus 11.6 mmol/L [P = 0.05]). In pork insulin-treated patients greater values while on human insulin were found for mean glucose (9.0 mmol/L [pork] versus 9.7 mmol/L [human insulin], P = 0.05), 'M' index (65.0 [pork] versus 79.6 [human insulin], P less than 0.025), and total daily insulin dose (50.9 U/day [pork] versus 52.5 U/day [human insulin], P less than 0.001). The early morning glucose sample was also greater on human insulin (9.6 mmol/L [pork] versus 12.1 mmol/L [human insulin], P less than 0.001). No significant differences in either insulin antibody levels or E. coli protein antibody levels were found between either of the animal-insulin treatment periods and human insulin treatment periods.(ABSTRACT TRUNCATED AT 250 WORDS)