The objective of this study was to investigate the existence of abnormalities of insulin sensitivity in patients with chronic heart failure. Glucose metabolism and insulin resistance were assessed in 10 male patients with severe, chronic heart failure and in 10 matched control subjects. Glucose, insulin and C-peptide concentration profiles were measured following a 0.5 g.kg-1 intravenous glucose tolerance test. Insulin sensitivity (inversely related to insulin resistance) was estimated by minimal modelling analysis of the glucose and insulin profiles. Heart failure patients had similar mean fasting plasma glucose concentration to controls but a significantly greater mean fasting plasma insulin concentration (P = 0.002) and C-peptide concentration (P = 0.02). Plasma glucose response profile was similar in the two groups but the incremental plasma insulin response profile of the heart failure group was significantly greater (P = 0.004). Mean insulin sensitivity was 73% lower in the heart failure patients (P = 0.003). These findings show that patients with severe chronic heart failure are hyperinsulinaemic and insulin resistant compared with a matched health group. This insulin resistance and hyperinsulinaemia may contribute to the progressive deterioration in myocardial function and associated clinical features of fatigue and reduced exercise tolerance seen in heart failure. Interventions designed to overcome or reduce insulin resistance warrant further investigation.

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SummaryThe mortality rate from ischaemic heart disease (I.H.D.) has increased in young women by about 50% in 12 years, and it is now possible to report the findings in 150 women who developed symptoms Hypercholesterolaemia, hypertension, or excessive cigarette smoking each occurred in a large minority, and more than one of these major risk factors was present in most patients. Hypercholesterolaemia was the commonest factor. In women in whom lipoprotein typing was undertaken the type II pattern was more frequent than type IV. The prevalence of hypercholesterolaemia and hypertension was the same in those with myocardial infarction and in those with angina.Excessive cigarette smoking was more common in women with myocardial infarction than in those with angina. The latter did not differ in their cigarette smoking habits from the normal population.A premature menopause had occurred in 20% of these women, but there was no relation between the early onset of I.H.D. with age at menarche, parity, or the incidence of abortion. Oral contraceptives did not increase the risk of myocardial infarction unless one of the major risk factors was also present.Altogether 75% of patients with angina or myocardial infarction survived 12 years. Coexisting hypertension worsened the prognosis. The prognosis after myocardial infarction was similar in these women to that previously described for men under the age of 40.

Relations between serum lipids, lipoproteins, blood pressure, and insulin metabolism were investigated in 158 healthy men aged 19-77 years and with body mass indexes (BMIs) of 19-41 kg • m" 2 . Mathematical modeling analysis of glucose, insulin, and C-peptide concentrations during an intravenous glucose tolerance test was used to measure parameters of insulin metabolism. In univariate analysis, both fasting and postglucose insulin concentrations showed significant positive associations with fasting serum triglyceride levels (r=0-33 and 0.38, respectively) and systolic (r=022 and 0.26) and diastollc (r=0.21 and 0.24) blood pressure and negative associations with high density lipoprotein subtraction 2 cholesterol (HDL 2 ; r=-0.21 and -0.25). In multivariate analysis, the associations between insulin and HDL 2 cholesterol concentrations were found to depend on triglyceride levels. Insulin resistance and basal pancreatic insulin secretion showed significant positive associations with serum triglycerides, which were independent of the effects of age, BMI, and fat distribution. Hepatic insulin throughput was independently associated with HDL 2 cholesterol. Associations of insulin-related variables with blood pressure were generally dependent on age and BMI. These results underline the importance of insulin sensitivity and insulin concentrations as determinants of triglyceride metabolism. They also indicate a close relation between hepatic insulin handling and HDL] concentration that is independent of triglyceride metabolism. has lent support to the possibility that elevated insulin concentrations may have a direct role in atherogenesis. 4 Furthermore, elevated insulin concentrations are associated with raised blood pressure 5 and serum triglyceride concentrations 6 and with reduced serum high density lipoprotein (HDL) cholesterol concentrations, 7 factors that in themselves may increase coronary heart disease risk.Resistance of glucose elimination to insulin action (insulin resistance) is a major determinant of the plasma insulin concentration 8 and may have a stronger relation with cardiovascular disease risk factors than does plasma insulin concentration.9 -11 Determinants of insulin concentrations, such as insulin resistance, may therefore be more directly involved in the relations between insulin and cardiovascular disease risk than are the insulin concentrations themselves. Computer modeling of plasma glucose, insulin, and C-peptide concentrations during an intravenous glucose tolerance test (FVGTT) allows quantification of the determinants of plasma insulin concentrations, which may be otherwise difficult to measure. We have used this technique in a large group of healthy men to investigate the associations of serum lipid and lipoprotein concentrations and blood pressure with insulinrelated variables. A wide range of variation in age and adiposity in this group provided the necessary variation in insulin metabolism against which these associations could be examined. Methods SubjectsWe studied 158 apparently heal...