Primary systemic amyloidosis: a review and an experimental, genetic, and clinical study of 29 cases with particular emphasis on the familial form. 1956.
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Biomedical subjects
Publications and source records attributed to W D Block.
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The relation of age and body mass index (BMI) to atherosclerosis risk factors was examined in 357 men. Older (greater than or equal to 45 years) men had higher (p less than 0.01) systolic and diastolic blood pressures, fasting cholesterol and glucose, and 1-hour glucose and insulin levels. Fasting insulin and triglyceride levels were not significantly different between the 2 age groups. Although older men (n = 170) had greater values for several risk factors, overweight (BMI greater than 25.5 kg/m2) increased risk factors more in men younger than 45 years (n = 187). In younger men, those with higher BMIs had a greater prevalence, respectively, of blood pressure greater than 140/90 mm Hg (35.2 vs 11.2%, p less than 0.0001), cholesterol greater than 200 mg/dl (53.5 vs 29.3%, p less than 0.001), fasting triglycerides greater than 150 mg/dl (38.0 vs 10.3%, p less than 0.0001), 1-hour glucose greater than 160 mg/dl (15.5 vs 5.2%, p less than 0.05), fasting insulin greater than 11 microU/ml (28.2 vs 5.2%, p less than 0.0001), and 1-hour insulin greater than 110 microU/ml (28.2 vs 9.5%, p less than 0.001). In contrast, among older men, the prevalence of elevated blood pressure, cholesterol, triglycerides and glucose values was not significantly greater in the subgroup with high BMI. However, elevations of fasting (19.6 vs 6.4%, p less than 0.05) and 1-hour insulin (29.3 vs 11.5%, p less than 0.01) values were more common among older men with higher BMIs.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood glucose and insulin responses to oral glucose were measured in 33 men: 8 normal, 13 with borderline carbohydrate-lipid metabolism disturbance (BCLMD) (pre-beta-lipoproteinemia with normal cholesterol and triglyceride levels), and 12 with mild Type IV hyperlipoproteinemia. Average age was 30 years, and the percentage of ideal weight was 101%. Borderline patients exhibited hyperinsulinemia following oral glucose, notably at 30 min; they also demonstrated an apparent impairment in homeostatic control of blood glucose level, with a greater-than-normal decline in blood glucose in the 3- to 4-h period (by profile analysis). The Type IV patients, though of normal weight and adiposity, exhibited elevated late incremental insulin area (LIIA) (1-5 h) responses. Combining all data, fasting triglycerides correlated with LIIA (p = 0.0002); LIIA correlated with the percentage of adipose mass (p = 0.003), suggesting that LIIA reflects insulin resistance. Lipoprotein electrophoresis remains useful for detecting pre-beta-lipoproteinemia, which may occur even in persons with normal cholesterol and triglyceride levels. When present, it suggests the possibility of hyperinsulinemia following glucose ingestion, which in turn has been shown to be an independent predictor for the development of coronary heart disease. To gain increased understanding of the natural history of hypertriglyceridemia, persons with BCLMD should be studied separately from those with normal lipid and carbohydrate metabolism and from those with hypertriglyceridemia.
The effects of 9 weeks of moderate intensity exercise training while on a weight-maintaining diet were studied in 19 untrained middle-aged, hypertriglyceridaemic, carbohydrate intolerant men. Initial mean maximum oxygen consumption was low (29.7 +/- 1.0 ml.min-1.kg-1; mean +/- SEM) and improved (34.2 +/- 1.4 ml.min-1.kg-1, p less than 0.01) with exercise training. Fasting glucose, insulin, lipid and lipoprotein concentrations did not change. While the abnormal glucose response to oral glucose did not change with training, insulin concentrations were significantly (p less than 0.05) lower at 90 and 120 min during the final oral glucose tolerance test. Insulin mediated glucose uptake did not change, indicating that the degree of exercise training failed to improve in vivo insulin sensitivity. Significant associations were found between the following parameters measured: fasting concentrations of triglycerides and insulin, very low density lipoprotein-triglycerides and glucose, and measures of in vivo insulin resistance and fasting insulin levels, suggesting that insulin resistance in these glucose intolerant subjects may play a role in their hypertriglyceridaemia. These data indicate that moderate increases in physical training alone are not sufficient to improve the carbohydrate, insulin and lipid metabolism of hypertriglyceridaemic, glucose intolerant men.
The effects of 9 weeks of aerobic exercise training with maintenance of stable body weight upon insulin sensitivity and upon glucose, lipid, and lipoprotein concentrations were studied in 10 middle-aged men with mild hypertriglyceridemia. Following training, mean maximum oxygen consumption improved from 33.5 +/- 1.9 to 39.3 +/- 1.9 mL/kg/min (means +/- SEM), (P less than 0.01). Glucose concentrations, both fasting and during oral glucose tolerance testing, remained stable but both fasting insulin concentrations and insulin responses to oral glucose decreased (P less than 0.1 and less than 0.01, respectively). In vivo insulin sensitivity improved 25 +/- 6.1% (P less than 0.01) following training. Exercise training resulted in decreases in fasting serum triglyceride concentrations from 203 +/- 12.6 to 126 +/- 9.0 mg/dL (P less than 0.01), primarily as a result of the reduction in VLDL-triglycerides (P less than 0.01). The magnitude in percentage decrease of VLDL-triglycerides was found to be significantly correlated (r = 0.71, P less than 0.05) with the magnitude in percent increase in max VO2. Serum cholesterol levels declined from 211 +/- 8.9 to 193 +/- 11.9 mg/dL (P less than 0.01), and the ratio of HDL-cholesterol to total cholesterol was improved. This study demonstrates that exercise training at a level of intensity feasible for many middle-aged men has beneficial effects on several factors that have been associated with an increased risk of cardiovascular disease.
We studied the effects of exercise training on plasma lipid and lipoprotein concentrations of rats on a high-fat and high-cholesterol diet. Twelve weeks of training occurred at moderate [Mod-Exer, 70% peak O2 consumption (VO2)] and high (High-Exer, 82% peak VO2) intensities. The duration of daily training sessions was adjusted to maintain equivalent energy expenditure between groups. Following training, body weight and lean body mass were 10% lower in the High-Exer group than the Mod-Exer or control groups. Compared with control values, carcass fat content was 33% lower for both trained groups. The oxidative capacity of skeletal muscle was approximately 30% greater in the trained groups compared with the control group. Total cholesterol, high density lipoprotein cholesterol, and total triglyceride concentrations in plasma were not different between the trained groups, but were 33-47% lower compared with the control group. The exercise-induced changes in plasma lipid and lipoprotein concentrations may be a result of a change in preferred substrate utilization in skeletal muscle toward a greater oxidation of lipid.
We studied two sisters 29 and 31 years old who had skin and tendon xanthomas, corneal clouding, and severe coronary atherosclerosis. Histologic examination showed collections of lipid-laden histiocytes in the skin. The patients' plasma cholesterol concentrations were 177 and 135 mg per deciliter (4.58 and 3.49 mmol per liter). Levels of high-density-lipoprotein cholesterol were 4 and 7 mg per deciliter (0.1 and 0.2 mmol per liter). Only traces of apolipoprotein A-I were detected in whole plasma. The plasma density fraction from 1.06 to 1.21 g per milliliter contained no high-density lipoprotein on high-pressure liquid chromatography, no apolipoprotein A-I on sodium dodecyl sulfate electrophoresis, and only traces of apolipoprotein A-I on radioimmunoassay. Apolipoprotein C-III was also not detectable. The activity of lecithin-cholesterol acyltransferase was 40 per cent of normal. The half-life of infused normal high-density lipoprotein was three days (normal, 5.8 days). The parents and children of these two patients had low levels of high-density-lipoprotein cholesterol and apolipoprotein A-I. These cases support the hypothesis that low concentrations of high-density lipoprotein promote atherosclerosis.
Physiological variables were compared among women who had never used oral contraceptives, past users, and current users. Randomly selected subjects were aged 30 to 59 years. Blood was sampled for determination of blood glucose, serum cholesterol and triglyceride, and plasma insulin concentration. Summed postchallenge glucose and insulin values were used in analyses to represent the magnitude of response. Contours of glucose and insulin curves were represented by single numerical variables termed "G-CON" and "I-CON." Current users of oral contraceptives had significantly higher values of G-CON, I-CON, triglyceride, and systolic blood pressure than women who never used oral comtraceptives. Current users also had significantly higher levels of summed glucose, G-CON, and I-CON than former users. Use of currently prescribed oral contraceptives is associated with adverse physiological changes that are reversible after discontinuing such use.
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Serum lipids, plasma insulin and glucagon, aerobic capacity, and body composition were examined in middle-aged men (X age = 44.2 years) with type IV hyperlipoproteinemia to determine the relative effectiveness of a caloric restricted type IV hyperlipoproteinemia diet (group A) versus physical training plus an isocaloric type IV diet (group B). After 9 weeks of the above interventions, reductions (P less than 0.01) in mean cholesterol levels from 213 to 186 (12% change) and from 205 to 185 mg/dl (9% change), and in triglyceride levels from 332 to 211 (29% change) and from 263 to 138 mg/dl (42% change) were found for groups A and B, respectively. A small reduction in mean fasting insulin level was found only in group B; this reduction appeared inversely associated with increases in aerobic capacity in group B (r = -0.66). Both interventions were without effect on fasting glucagon levels. The physical training program prescribed resulted in a 12% increase in aerobic capacity (group B). Significant mean body weight reductions of 7.7 lb (P less than 0.01) and 2.9 lb (P less than 0.01) were seen for groups A and B, respectively; these absolute body weight reductions differed significantly (P less than 0.05) between groups. Both groups significantly lost body fatness (P less than 0.01). These reductions in body weight and body fatness appeared independent of changes in lipid levels. These results demonstrate that both interventions reduce serum lipids in men with type IV hyperlipoproteinemia but that physical training plus an isocaloric type IV diet may be the more advantageous of the two regimens, since a greater percentage decrease and a more sustained reduction in serum triglyceride levels, and a greater reduction of fasting hyperinsulinemia were observed in group B.
A random sample of 568 participants in the Tecumseh, Mich, study, aged 30 to 59 years, was stratified according to blood glucose concentration to select a high proportion of diabetics. Subjects were categorized as overt diabetics, chemical or probable diabetics, or nondiabetics. Diabetic groups and nondiabetics were compared for levels of blood glucose, plasma insulin, serum cholesterol, serum triglyceride, blood pressure, and contours of glucose and insulin curves. Overt diabetics had high mean fasting blood glucose levels. Challenged diabetics had significantly higher concentrations of all variables except cholesterol than nondiabetics, even after adjustment for age and adiposity. Glucose intolerance, adiposity, and sex influenced variables independently. Risk of atherosclerosis is partly attributable to persistent hyperglycemia and related metabolic abnormalities in overt diabetics. Postchallenge diabetics have subtle hyperglycemia but a high frequency of other risk factors. Recent developments suggest that control of blood glucose may become feasible and useful in the prevention of cardiovascular disease in overt and challenged diabetics.
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Age 10-69, 793 males and 80 females were tested on the treadmill as they walked at 4.83 km per hour (3.27 km per hour in subjects 60 years and older). Every three minutes, the grade was increased 3%. Maximal oxygen uptake (VO2max.) and related measurements were recorded during the third minute at each grade. Subjects age 10-39 exercised to exhaustion and VO2max. was measured. In subjects age 40-69, VO2max. was estimated from sub-maximal VO2 and heart rate. The sum of four skinfolds, serum uric acid (SUA) and one-hour glucose tolerance were also measured on these subjects. Body fatness was positively correlated with SUA and blood glucose and negatively correlated with VO2max. Age was negatively correlated with VO2max. and positively correlated with blood glucose. After removing the effects of age, weight and fatness, the correlation of VO2max. and SUA was low. Similarly, there was little or no correlation between VO2max. and blood glucose after the effects of age, weight and fatness were removed.
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