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Biomedical subjects

L J Bennion

Publications and source records attributed to L J Bennion.

At least 19 recordsLinked to original sources

Sustained reduction of proteinuria in type 2 (non-insulin-dependent) diabetes following diet-induced reduction of hyperglycaemia.

To determine whether sustained control of hyperglycaemia in Type 2 (non-insulin-dependent) diabetic patients would diminish proteinuria, the effect of hypocaloric diet therapy (500 kcal/day) on proteinuria was assessed in obese, Type 2 diabetic patients (n = 24) and compared with results obtained for obese subjects with normal glucose tolerance (n = 7) and impaired glucose tolerance (n = 6). Diet therapy of similar mean duration resulted in similar percentage weight loss (mean percentage of original weight +/- SEM) in diabetic (13.6 +/- 1.6%), glucose intolerant (16.4 +/- 3.3%) and obese non-diabetic (11.0 +/- 1.0%) subjects. Following therapy, plasma glucose concentrations 2h after an oral glucose load declined in the diabetic (18.34 +/- 0.81 to 10.67 +/- 0.50 mmol/l, mean +/- SEM; p less than 0.001) and in the glucose intolerant subjects (10.2 +/- 0.3 to 7.3 +/- 0.4 mmol/l, p less than 0.01) while remaining unchanged in the obese non-diabetic subjects (7.09 +/- 0.23 to 6.77 +/- 0.32 mmol/l, NS). Concentrations of total protein of plasma origin and albumin in 24-h urine collections were quantified by a sensitive immunonephelometric assay using specific antisera. Initially, 24-h excretion of total protein and albumin were elevated in the diabetic [mg protein/24 h; (median +/- 95% confidence limits): 63 (42-138), p less than 0.05; albumin: 26 (14-56), p less than 0.05] and glucose intolerant subjects [protein: 52 (13-92), NS; albumin: 24 (3-61), NS] compared with the non-diabetic subjects [protein: 20 (5-38); albumin: 6.2 (3.5-9.5)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Diminished effect of caloric restriction on control of hyperglycemia with increasing known duration of type II diabetes mellitus.

The effect of weight loss and caloric restriction on plasma glucose concentrations and insulin and glucagon secretion in response to oral and iv glucose and arginine infusions was examined in 8 subjects with type II diabetes mellitus of greater than 5 yr duration (long term diabetes). The findings of this study were compared to previous results in 10 subjects with similar degrees of obesity and fasting hyperglycemia but diabetes of less than 2 yr duration (recent-onset diabetes; fasting plasma glucose, 267 +/- 16.5 mg/dl in long term diabetics and 259 +/- 8.0 mg/dl in recent onset diabetics) and to a control group of 8 similarly obese but nondiabetic subjects. Both diabetic groups had impaired insulin responses on initial and final tests compared to control subjects. Response to dietary therapy was significantly poorer in the diabetics of longer duration (final fasting plasma glucose, 175 +/- 18.9 mg/dl in long term vs. 119 +/- 6.2 mg/dl in recent-onset subjects; P less than 0.01) despite a similar degree of weight loss and duration of diet therapy in the 2 groups. This difference in glucose tolerance occurred despite similar final insulin and glucagon responses in the diabetic groups. Subjects with type II diabetes of long duration appear to have a relatively greater degree of insulin resistance than subjects with more recent onset of the disease.

Adult↗

Oral contraceptives raise the cholesterol saturation of bile by increasing biliary cholesterol secretion.

To discover the mechanism by which oral contraceptives increase the level of cholesterol saturation of human bile, we measured biliary lipid secretion rates, gallbladder and hepatic bile lipid composition, bile acid pool size, bile acid composition, and plasma lipoprotein levels in five healthy women during routine oral contraceptive treatment and again during normal menstrual cycles on no medication. The molar percent cholesterol in both gallbladder and hepatic bile was higher in every subject while taking oral contraceptives (p less than .02). Oral contraceptive usage was accompanied by a significant enhancement of biliary cholesterol secretion (65 versus 46 mg/hr, p less than .01), but there was no significant change in bile acid or phospholipid secretion, total bile acid pool size, or bile acid composition. These findings indicate that oral contraceptive usage increases biliary cholesterol secretion, thereby raising the level of cholesterol saturation of bile and predisposing to cholesterol precipitation and gallstone formation.

Adult↗

Studied of very low density lipoprotein triglyceride metabolism in an obese population with low plasma lipids: lack of influence of body weight or plasma insulin.

Pima Indians have a high prevalence of hyperinsulinemia, obesity, and diabetes, but they have low plasma cholesterol levels, reduced low density lipoprotein synthesis, and little arteriosclerotic heart disease. To investigate lipoprotein metabolism further in this group, very low density lipoprotein (VLDL) metabolism was studied, using [3H]glycerol as an endogenous precursor of triglyceride (TG) synthesis, in 15 obese Pima nondiabetic males and compared to that of 10 obese and 13 normal weight, normolipidemic, nondiabetic Caucasian males. The resultant kinetic data were analyzed using a multicompartmental model which includes two pathways for VLDL-TG synthesis and a process of stepwise delipidation for VLDL catabolism. As compared to obese Caucasians, the obese Pimas had a lower rate of VLDL-TG synthesis, and a lower proportion of slow pathway for synthesis. The fractional catabolic rate in the Pimas was higher than in either Caucasian group, a larger proportion of VLDL-TG was delipidized at each step, and particle residence time was shorter. When the relation between VLDL-TG metabolism and plasma insulin was examined, plasma insulin levels in the Pima were not correlated with VLDL-TG synthetic rates, catabolic rates, or plasma pools. On the other hand VLDL-TG synthetic rates were correlated with plasma free fatty acid levels. Thus, in this population with low plasma lipids and reduced arteriosclerotic heart disease, VLDL-TG synthesis is low, VLDL-TG catabolism is accelerated, and VLDL pools appear to be insensitive to the influence of body weight and hyperinsulinemia.

Adolescent↗

Development of lithogenic bile during puberty in Pima indians.

To determine whether highly saturated bile is a congenital or acquired characteristic of Pima Indians and to elucidate the basis of the rapid postpubertal increase in gallstones in Pimas, we studied the bile of 66 Pimas nine to 21 years of age. Highly saturated bile is not prevalent among Pimas under the age of 13, but bile saturation increases significantly (P less than 0.05) in both sexes during pubertal growth and development. Bile saturation was 15 per cent higher in females than males. Bile acid pools increased with age in the young men, but not in women. Bile cholesterol saturation correlated with obesity (r = 0.41; P less than 0.001) and urinary estrogen excretion (r = 0.44; P less than 0.001). Highly saturated bile may be present for several years before the onset of cholesterol cholelithiasis.

Adolescent↗

Changes in plasma lipoproteins accompanying diet therapy in obese diabetics.

Plasma lipoprotein cholesterol and triglyceride levels were measured in 24 obese not-insulin dependent Pima Indian diabetics and 9 obese nondiabetic controls before and after 1-8 months on a 500 calorie diet. The diabetics were divided into 3 groups--severe, recent onset (n = 10), severe long-term (n = 6), and borderline (n = 8). The diet regimen resulted in weight loss and improved glucose tolerance in all of the diabetics, and insulin secretion increased in the 2 groups of severe diabetics. After the period of weight loss, total plasma cholesterol had declined greater than 20%, and LDL cholesterol decreased 25% in all diabetic groups and in the controls. In all diabetic groups, HDL cholesterol did not decline; therefore the ratio of HDL/LDL cholesterol after diet therapy was significantly increased. In the controls HDL cholesterol declined with weight loss, and the distribution of HDL/LDL cholesterol remained constant. Plasma and VLDL triglyceride levels decreased in all groups in those with initial triglyceride levels greater than 150 mg/dl. The results indicate that weight loss in not-insulin dependent diabetics not only improves glucose tolerance, but also lowerss plasma lipids and reverses the dyslipoproteinemia often associated with this disorder. This may influence the risk of arteriosclerotic heart disease in these individuals.

Adult↗

Normalization of insulin and glucagon secretion in ketosis-resistant diabetes mellitus with prolonged diet therapy.

Glucose tolerance and insulin and glucagon secretion were examined sequentially during 6 months of calorie and carbohydrate restriction in an obese, recent-onset, ketosis-resistant diabetic adult. The subject was then followed for 9 additional months, during which some weight was regained. Fasting plasma glucose levels returned to normal after 6 week of calorie restriction and remained normal during periods of carbohydrate refeeding. Normalization of 2-h plasma glucose concentrations after a standard oral carbohydrate load required 5 months, and glucose disposal after an iv glucose load did not return to normal until the end of the study. Insulin secretion in response to oral glucose reached maximal levels during the first months of weight reduction and then decreased as glucose tolerance continued to improve. Acute phase insulin release in response to iv glucose gradually increased throughout the study. Glucagon stimulation by iv arginine and suppression by iv glucose also returned to normal levels slowly over several months. Abnormalities in glucose tolerance and glucoregulatory hormone secretion of ketosis-resistant diabetes are totally reversible with prolonged dietary therapy. Reduction in tissue resistance to the action of insulin also appeared to be of major importance in the recovery of normal glucose tolerance in this subject.

Adult↗

Lipoprotein composition in diabetes mellitus.

Lipoprotein cholesterol and triglyceride levels have been determined in normal and diabetic Pima Indian women aged 20-35, HDL cholesterol levels were lower, LDL cholesterol levels were higher, and the ratio of HDL cholesterol/LDL cholesterol, a reflection of lipoprotein cholesterol distribution, was lower in the diabetics compared to the normals. VLDL triglyceride levels were also elevated in the diabetics. An analysis of lipoprotein composition suggested that these changes primarily reflect changes in numbers of particles, since lipid composition and lipid/protein ratios were similar in lipoproteins isolated from normals and diabetics. The ratio of ester/free cholesterol in LDL and HDL was lower in normal Pima Indians than in a comparable group of Caucasians, although plasma LCAT activity was not significantly different. The data indicate that diabetes may be associated with shifts in distribution of LDL and HDL, as well as with increases in VLDL.

Adult↗

Sex differences in the size of bile acid pools.

In view of the excess prevalence of gallstones among women and the association of gallstones with diminished bile acid pool size, we measured bile acid pools in 27 male and 25 female healthy human volunteers. The average bile acid pool in the women was significantly smaller than in the men (2.25 +/- .12 g versus 2.88 +/- .16 g; p = 0.003). Chenodeoxycholic acid pool size, computed from bile acid composition data available in 43 of these subjects, was also smaller in women than men (0.94 +/- 0.06 versus 1.22 +/- 0.07 g; p = 0.004). Age, race, and body size bore no statistically significant relationship to bile acid pool size. Biliary cholesterol saturation was positively correlated with weight and obesity and showed a significant inverse correlation with chenodeoxycholic acid pool size, but not with total bile acid pool size. These findings suggest a possible mechanism for the higher prevalence of gallstones among women.

Adolescent↗

Effects of diabetes mellitus on cholesterol metabolism in man.

In view of the reported excess prevalence of atherosclerosis and cholelithiasis in diabetes, we investigated several aspects of cholesterol metabolism under metabolic ward conditions in six Pima Indians with maturity-onset diabetes mellitus. Cholesterol balance (13.5 versus 11.0 mg per kilogram per day, P less than 0.05), fecal bile acid excretion (415 versus 261 mg per day, P less than 0.05), bile acid pool size (3150 versus 1950 mg, P less than 0.05), fasting plasma cholesterol (193 versus 160 mg per deciliter, P less than 0.05) and plasma triglycerides (251 versus 150 mg per deciliter, P less than 0.05) were higher during uncontrolled hyperglycemia than during relative euglycemia on insulin. The increased plasma lipid levels and total cholesterol synthesis during hyperglycemia may contribute to the acceleration of atherosclerosis in diabetes mellitus. Gallbladder bile was significantly more saturated with cholesterol (181 per cent versus 114 per cent, P less than 0.05) during insulin treatment than during uncontrolled hyperglycemia. Bile lipid composition was thus more favorable to cholesterol precipitation and gallstone formation during insulin treatment than in the untreated diabetic state.

Adult↗

Effects of oral contraceptives on the gallbladder bile of normal women.

In view of the reported association between use of oral contraceptives and gallbladder disease, the effects of contraceptive steroids on the lipid composition of gallbladder bile were studied in 22 healthy women. Each subject was studied during routine use of oral contraceptives and also during normal menstrual cycles on no medication. Gallbladder bile was significantly more saturated with cholesterol during contraceptive therapy than during normal menstrual cycling (125 versus 92 per cent, P less than 0.001). Chenodeoxycholic acid accounted for a significantly smaller proportion (35 versus 42 per cent P less than 0.001) and cholic acid a significantly greater proportion (50 versus 41 per cent (P less than 0.001) of total bile acids during contraceptive steroid therapy. These findings show that exogenous sex steroids in doses and formulations routinely prescribed induce important alterations in the composition of human gallbladder bile, and suggest a biochemical basis for the increase in gallbladder disease observed among women using oral contraceptives.

Adult↗