Biomedical subjects

A L Swislocki

Publications and source records attributed to A L Swislocki.

33 records · Page 2Linked to original sources

PubMed1989

Effect of prazosin treatment on carbohydrate and lipoprotein metabolism in patients with hypertension.

This study evaluated the effect of prazosin in controlled mild hypertension and evaluated select metabolic changes that occurred with prazosin monotherapy. Various aspects of glucose, insulin, and lipid metabolism were studied before and after approximately 10 weeks of prazosin treatment in 12 patients with mild hypertension. Prazosin was well tolerated and induced a significant decrease (p less than 0.001) in both systolic and diastolic blood pressures, without any change in body weight. Plasma concentrations of glucose, free fatty acid, and lactate, which were measured hourly from 8 A.M. to 4 P.M. following meals consumed at 8 A.M. and noon, did not change with prazosin treatment. However, the plasma insulin response from 8 A.M. to 4 P.M. decreased significantly (p less than 0.001) following prazosin treatment. In addition, fasting plasma triglyceride and cholesterol concentrations were significantly lower (p less than 0.05) in prazosin-treated persons, as were postprandial triglyceride concentrations (p less than 0.001). Lower total plasma triglyceride and cholesterol concentrations were accounted for by decreases in very low-density lipoprotein cholesterol and triglyceride and low-density lipoprotein cholesterol and triglyceride, whereas both high-density lipoprotein triglyceride and high-density lipoprotein cholesterol concentrations increased following prazosin treatment. Finally, although both apolipoprotein A1 and apolipoprotein B concentrations decreased in association with prazosin treatment, the decrease in apolipoprotein B was much greater in magnitude, leading to an increase in the ratio of apolipoprotein A1 to apolipoprotein B. In this study, treatment of mild hypertension with prazosin led to lower blood pressures and changes in insulin and lipoprotein metabolism that are important in this patient population.

Adult↗

PubMed1989

Insulin resistance, glucose intolerance and hyperinsulinemia in patients with hypertension.

Plasma glucose and insulin responses to an oral glucose challenge and insulin-stimulated glucose uptake were measured in 47 age-, weight-, and sex-matched lean white men (16 with normal blood pressure, 14 with untreated hypertension, nine treated with a thiazide diuretic only, and eight treated with combined diuretic and beta-adrenergic antagonist drugs). Following a 75-g glucose dose, plasma glucose and insulin were measured for a three-hour period. In separate studies, insulin-stimulated glucose uptake was estimated by measuring the steady-state plasma glucose (SSPG) and insulin (SSPI) concentrations achieved during the last 30 minutes of a 180-minute continuous infusion of somatostatin, insulin, and glucose (insulin suppression test). Under these conditions endogenous insulin secretion was suppressed, and differences in SSPG concentration allowed comparisons of the ability of exogenous insulin to stimulate disposal of an identical glucose load in different individuals. The results indicated that men with untreated hypertension had significantly elevated plasma glucose (P less than .001) and insulin concentrations (P less than .001) after an oral challenge compared to normal volunteers. Mean SSPG concentrations were also higher (P less than .05) than normal in patients with untreated hypertension.2+ Furthermore, plasma glucose and insulin concentrations after the oral glucose challenge and SSPG concentration during the insulin suppression test were higher in treated than in treated patients than in untreated patients with hypertension. These results confirm earlier observations that untreated patients with hypertension are insulin resistant, hyperglycemic, and hyperinsulinemic compared to a well-matched normotensive control group, and suggest that conventional treatment programs for lowering blood pressure many exaggerated these metabolic defects.

Contraceptives, Oral, Combined↗

PubMed1989

Persistence of hypertriglyceridemic effect of low-fat high-carbohydrate diets in NIDDM patients.

Although low-fat high-carbohydrate diets are recommended for patients with non-insulin-dependent diabetes mellitus (NIDDM) in an effort to reduce the risk of coronary artery disease (CAD), the results of short-term studies have shown that these diets can lead to changes in carbohydrate and lipid metabolism associated with an increased risk of CAD. This study has extended these earlier observations by determining the metabolic effects of such diets over a longer period in these patients. The comparison diets contained either 40 or 60% of the total calories as carbohydrates, with reciprocal changes in fat content from 40 to 20% consumed in random order for 6 wk in a crossover experimental design. The ratio of polyunsaturated to saturated fat and the total cholesterol intake were held constant in the two diets. Plasma glucose and insulin concentrations were significantly (P less than .001) elevated throughout the day when patients consumed the 60% carbohydrate diet, and 24-h urinary glucose excretion more than doubled (0.8 vs. 1.8 mol/24 h). Fasting plasma total and very-low-density lipoprotein (VLDL) triglyceride (TG) concentrations increased by 30% (P less than .001) after 1 wk on the 60% carbohydrate diet, and the magnitude of carbohydrate-induced hypertriglyceridemia persisted unchanged throughout the 6-wk study period. Total plasma cholesterol concentrations were similar after both diets. However, VLDL cholesterol (VLDL-chol) was significantly increased, whereas both low-density lipoprotein (LDL-) and high-density lipoprotein (HDL-) chol concentrations were significantly decreased after consumption of the 60% carbohydrate diet. Consequently, neither total-chol-to-HDL-chol nor LDL-chol-to-HDL-chol ratios changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1988

Effect of enprostil on plasma glucose, insulin and lipid metabolism in patients with non-insulin-dependent diabetes mellitus.

Measurements of various aspects of glucose, insulin and lipid metabolism were made before and after the administration of enprostil (a synthetic dehydroprostaglandin E2) for one week to ten patients with non-insulin-dependent diabetes mellitus (NIDDM). Both fasting (P less than 0.01) and postprandial (P less than 0.001) plasma glucose concentrations were significantly lower after one week of enprostil, and 24 hour urinary glucose excretion was reduced from (mean +/- SEM) 47 +/- 14 to 25 +/- 9 g/day. There was no change in either fasting or postprandial insulin concentration, but the postprandial GIP response was also significantly reduced (P less than 0.001). In addition, there were significant reductions in postprandial plasma free fatty acid (P less than 0.05) and triglyceride (P less than 0.001) concentrations, associated with a modest fall in fasting plasma triglyceride (P less than 0.05) and cholesterol (P less than 0.07) concentrations when measured after one week of treatment with enprostil. These results raise the possibility that enprostil may be of some benefit in the treatment of patients with non-insulin-dependent diabetes.

Aged↗

PubMed1988

Effect of time on measurement of hepatic glucose production.

Basal hepatic glucose production (HGP) was determined in obese and nonobese normal subjects and patients with noninsulin-dependent diabetes mellitus (NIDDM) using [3-3H]glucose and the nonsteady state equations of Steele. When HGP was estimated at hourly intervals from 0800-1300 h, it became evident that calculated values for HGP fell for the first 2-4 h until a plateau was reached, and this decline was quite precipitous during the first 2 h in patients with NIDDM. Furthermore, when the same patient with NIDDM was studied on two occasions, similar values for HGP were not uniformly obtained unless measurements were made at least 4 h after [3-3H] glucose administration. Since it has been the convention to use the nonsteady state equations of Steele to calculate HGP in patients with NIDDM 2 h after [3-3H] glucose administration, it is almost certain that published values for HGP in patients with NIDDM are falsely high. Based upon the data presented, we suggest that HGP using [3-3H]glucose and the nonsteady state Steele equations be measured for at least a 4-h period in patients with NIDDM in order to increase the validity of the calculated value.

Diabetes Mellitus, Type 2↗

PubMed1987

Insulin suppression of plasma-free fatty acid concentration in normal individuals and patients with type 2 (non-insulin-dependent) diabetes.

In order to define the effect of Type 2 (non-insulin-dependent) diabetes mellitus on the ability of insulin to regulate plasma-free fatty acid (FFA) concentrations, we determined the plasma FFA response to the intravenous infusion of various amounts of insulin. Plasma FFA concentrations were higher in patients with Type 2 diabetes (two way analysis of variance, p less than 0.001) over a plasma insulin concentration which ranged from approximately 5 to 55 mU/l of insulin. Although plasma FFA concentrations were higher in patients with Type 2 diabetes at any given insulin concentration, the relative ability of insulin to suppress plasma FFA concentration to half the initial value was comparable in normal individuals and patients with Type 2 diabetes, occurring at a plasma insulin concentration of approximately 20 mU/l. These data demonstrate that plasma FFA levels are regulated over a narrow range of plasma insulin concentrations in humans, and that plasma concentrations are higher than normal in patients with Type 2 diabetes throughout this range.

Aged↗

PubMed1987

Deleterious metabolic effects of high-carbohydrate, sucrose-containing diets in patients with non-insulin-dependent diabetes mellitus.

The effects of variations in dietary carbohydrate and fat intake on various aspects of carbohydrate and lipid metabolism were studied in patients with non-insulin-dependent diabetes mellitus (NIDDM). Two test diets were utilized, and they were consumed in random order over two 15-day periods. One diet was low in fat and high in carbohydrate, and corresponded closely to recent recommendations made by the American Diabetes Association (ADA), containing (as percent of total calories) 20 percent protein, 20 percent fat, and 60 percent carbohydrate, with 10 percent of total calories as sucrose. The other diet contained 20 percent protein, 40 percent fat, and 40 percent carbohydrate, with sucrose accounting for 3 percent of total calories. Although plasma fasting glucose and insulin concentrations were similar with both diets, incremental glucose and insulin responses from 8 a.m. to 4 p.m. were higher (p less than 0.01), and mean (+/- SEM) 24-hour urine glucose excretion was significantly greater (55 +/- 16 versus 26 +/- 4 g/24 hours p less than 0.02) in response to the low-fat, high-carbohydrate diet. In addition, fasting and postprandial triglyceride levels were increased (p less than 0.001 and p less than 0.05, respectively) and high-density lipoprotein (HDL) cholesterol concentrations were reduced (p less than 0.02) when patients with NIDDM ate the low-fat, high-carbohydrate diet. Finally, since low-density lipoprotein (LDL) concentrations did not change with diet, the HDL/LDL cholesterol ratio fell in response to the low-fat, high-carbohydrate diet. These results document that low-fat, high-carbohydrate diets, containing moderate amounts of sucrose, similar in composition to the recommendations of the ADA, have deleterious metabolic effects when consumed by patients with NIDDM for 15 days. Until it can be shown that these untoward effects are evanescent, and that long-term ingestion of similar diets will result in beneficial metabolic changes, it seems prudent to avoid the use of low-fat, high-carbohydrate diets containing moderate amounts of sucrose in patients with NIDDM.

Aged↗

PubMed1987

Relationships between plasma-free fatty acid concentration, endogenous glucose production, and fasting hyperglycemia in normal and non-insulin-dependent diabetic individuals.

Measurements of fasting and postprandial plasma glucose, insulin, and free fatty acid (FFA) concentrations were made in 32 individuals--16 with normal glucose tolerance and 16 with non-insulin dependent diabetes mellitus (NIDDM)--further subdivided into two equal groups on the basis of body weight. In addition, endogenous glucose production was estimated in 32 subjects. Both fasting plasma glucose (251 +/- 14 v 86 +/- 1 mg/dL) and FFA (672 +/- 35 v 434 +/- 45 microEq/L) concentrations were significantly higher in patients with NIDDM (P less than .001), and the differences between normal and diabetic existed in both weight groups. Rates of endogenous glucose production were also significantly elevated (P less than .001) in diabetic (120 +/- 6 mg/m2 X min) as compared to normal subjects (73 +/- 6 mg/m2 X min), and these differences were also independent of degree of obesity. However, there were no significant differences between normal subjects and patients with NIDDM in either fasting or postprandial insulin concentrations. The similarity in insulin values for normal and diabetic subjects was true of both obesity groups, although insulin concentrations were somewhat higher in normal obese individuals as compared to their normal nonobese counterparts. Significant relationships were seen between values for fasting plasma glucose and endogenous glucose production (r = .89), fasting plasma glucose and fasting FFA (r = .64), and FFA levels and endogenous glucose production (r = .58) when all nonobese subjects were considered together. Essentially identical relationships, both qualitatively and quantitatively, were seen within the obese group.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

PubMed1987

Improved insulin action in muscle, liver, and adipose tissue in physically trained human subjects.

The present studies were initiated to assess the effect of insulin on muscle, liver, and adipose tissue in eight control and eight physically trained individuals matched for age and body mass index. Results indicated that percent body fat was 53% lower and maximal oxygen consumption 50% higher in physically trained subjects. Although the plasma glucose response to a standard oral glucose challenge was similar in the two groups, the insulin response was significantly lower in the trained individuals (P less than 0.001). Mean (+/- SE) insulin-stimulated glucose uptake, quantified in vivo by the euglycemic hyperinsulinemic clamp technique, was significantly greater in physically trained individuals at steady-state plasma insulin concentrations of approximately 10 microU/ml (3.41 +/- 0.14 vs. 2.73 +/- 0.22 mg.kg fat free mass-1.min-1, P less than 0.05) and 50 microU/ml (13.58 +/- 0.75 vs. 9.82 +/- 0.53 mg.kg fat free mass-1.min-1, P less than 0.001). In addition, mean (+/- SE) hepatic glucose production rate was lower in physically trained subjects at insulin levels of 10 microU/ml (0.63 +/- 0.19 vs. 1.19 +/- 0.22 mg.kg body wt-1.min-1, P less than 0.05) and 50 microU/min (0.18 +/- 0.14 vs. 0.60 +/- 0.17 mg.kg body wt-1.min-1, P less than 0.05). Finally, the ability of insulin to stimulate mean (+/- SE) glucose uptake above basal levels was greater in adipocytes isolated from trained individuals (94 +/- 10 vs. 56 +/- 14 fl.cell-1.s-1, P less than 0.01). On the other hand, no difference in specific binding of insulin to its receptor on monocytes was noted between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1987

Documentation of hyperglucagonemia throughout the day in nonobese and obese patients with noninsulin-dependent diabetes mellitus.

Plasma glucose, insulin, FFA, glucagon, and GH concentrations were measured over an 8-h period in normal subjects and patients with noninsulin-dependent diabetes mellitus (NIDDM). Meals were consumed at 0800 h (20% of daily calories) and noon (40% of daily calories), and measurements were made hourly from 0800-1600 h. Day-long plasma glucose, insulin, and FFA concentrations were higher than normal (by two-way analysis of variance) in patients with NIDDM, whether obese or nonobese. In addition, day-long plasma glucagon concentrations were also higher than normal (by two-way analysis of variance) in both nonobese and obese patients with NIDDM. Furthermore, direct relationships were found between the total plasma glucagon response from 0800-1600 h and total plasma glucose (r = 0.57; P less than 0.001) and FFA (r = 0.30; P less than 0.06) responses. In contrast, plasma GH levels were not increased in patients with NIDDM. These data demonstrate that ambient plasma concentrations of both glucose and FFA are higher in patients with NIDDM, despite the fact that coexisting plasma insulin levels are equal to or higher than normal. The higher day-long plasma glucagon levels in patients with NIDDM may contribute to their higher plasma glucose and FFA concentrations.

Activity Cycles↗

PubMed1987

Resistance to insulin suppression of plasma free fatty acid concentrations and insulin stimulation of glucose uptake in noninsulin-dependent diabetes mellitus.

The ability of insulin to stimulate tissue glucose uptake and lower plasma FFA concentrations was quantified in 12 individuals with normal glucose tolerance and 12 patients with noninsulin-dependent diabetes mellitus (NIDDM), further subdivided into obese and nonobese subjects. Measurements were made during 5-h glucose clamp studies, carried out at plasma insulin concentrations of about 10 microU/ml (0-150 min) and about 60 microU/ml (150-300 min). Differences between the patient groups were compared by two-way analysis of variance. The ability of insulin to either suppress plasma FFA concentrations or stimulate glucose uptake was significantly reduced (P less than 0.001) in patients with NIDDM, and this was true of both the obese and nonobese groups. The defect in the ability of insulin to suppress plasma FFA concentrations in patients with NIDDM was more apparent at the lower insulin concentration, whereas resistance to insulin-stimulated glucose uptake in NIDDM was more dramatic at the high insulin concentration. Finally, a significant correlation (r = -0.67; P less than 0.001) between insulin-stimulated glucose uptake and plasma FFA concentration was found in the entire group. These data emphasize the fact that patients with NIDDM are resistant to multiple actions of insulin, and that the magnitudes of the defect in insulin suppression of plasma FFA levels and stimulation of tissue glucose uptake are roughly comparable.

Aged↗

PubMed1987

Can insulin resistance exist as a primary defect in noninsulin-dependent diabetes mellitus?

In this study we have attempted to quantify the plasma insulin response to glucose and insulin action in 22 nonobese subjects: 11 with normal glucose tolerance and 11 with mild [mean fasting plasma glucose concentration, 128 +/- (+/- SEM) 5 mg/dL] noninsulin-dependent diabetes mellitus (NIDDM). Estimates of the plasma insulin response were made by determining the plasma insulin concentration at hourly intervals from 0800-1600 h, before and after mixed meals consumed at 0800 h (breakfast) and 1200 h (lunch). Insulin action was assessed by measuring glucose uptake during insulin clamp studies performed at steady state plasma insulin levels of approximately 10 and 60 microU/mL, with the difference between the 2 values defined as insulin-stimulated glucose uptake. Plasma glucose (P less than 0.001) and insulin (P less than 0.001) concentrations were significantly higher in patients with NIDDM throughout the 8-h period (by two-way analysis of variance). However, mean (+/- SEM) insulin-stimulated glucose uptake was markedly reduced (P less than 0.001) in patients with type 2 diabetes mellitus (112 +/- 72 vs. 336 +/- 44 mg/m2 min-1). Thus, patients with NIDDM and mild fasting hyperglycemia were both insulin resistant and hyperinsulinemic compared to normal individuals. These data indicate that a defect in insulin-stimulated glucose uptake can occur in NIDDM in the absence of significant hyperglycemia and/or hypoinsulinemia.

Aged↗

PubMed1986

Effect of obesity on ambient plasma glucose, free fatty acid, insulin, growth hormone, and glucagon concentrations.

Fasting and postprandial plasma concentrations of glucose, FFA, insulin, glucagon, and GH concentrations were determined in 10 nonobese and 10 obese subjects with normal glucose tolerance. Measurements were made at 0800 h (after a 14-h fast) and at hourly intervals from then until 1600 h. During this time period all individuals ate breakfast at 0800 h (20% of total daily calories) and lunch (40% of total daily calories). Although plasma glucose concentrations were similar throughout the 8-h period in the 2 groups, plasma insulin concentrations were significantly (P less than 0.001) higher in the obese individuals. However, despite the presence of hyperinsulinemia, the obese group also had higher (P less than 0.001) plasma FFA concentration throughout the day. On the other hand, both the absolute and the relative declines in plasma FFA concentration after meals were similar in the 2 groups. Since plasma glucagon and GH concentrations were similar in the 2 groups, altered production of these lipolytic hormones was not responsible for the elevated plasma FFA levels in the obese individuals. These data document the presence in obese individuals of a disassociation in their ability to maintain normal plasma glucose as opposed to plasma FFA homeostasis, and indicate that the increase in plasma FFA concentrations in obesity occurs in the presence of hyperinsulinemia and is not related to abnormalities of either glucagon or GH secretion.

Adult↗

PubMed1985

Ambient plasma free fatty acid concentrations in noninsulin-dependent diabetes mellitus: evidence for insulin resistance.

Plasma glucose, insulin, and FFA concentrations were determined in 15 normal subjects and 15 patients with noninsulin-dependent diabetes mellitus (NIDDM) from 0800 to 1600 h. Breakfast and lunch were consumed at 0800 and 1200 h, respectively, and plasma concentrations were measured at hourly intervals from 0800-1600 h. Plasma glucose concentrations between 0800 and 1600 h were significantly elevated in patients with NIDDM, and the higher the fasting glucose level, the greater the postprandial hyperglycemia. Hyperglycemia in patients with NIDDM was associated with plasma insulin levels that were significantly higher (P less than 0.001) than those in normal subjects, and substantial hyperinsulinemia occurred between 0800 and 1600 h in patients with mild NIDDM (fasting plasma glucose concentrations, less than 140 mg/dl). Both fasting and postprandial FFA levels were also increased in patients with NIDDM (P less than 0.001), and the greater the plasma glucose response, the higher the FFA response (r = 0.70; P less than 0.001). However, there was no significant correlation between plasma insulin and FFA concentrations. More specifically, hyperinsulinemic patients with mild diabetes (fasting plasma glucose, less than 140 mg/dl) maintained normal ambient FFA levels, while FFA concentrations were significantly elevated in patients with severe NIDDM (fasting plasma glucose, greater than 250 mg/dl), with insulin concentrations comparable to those in normal subjects. These results demonstrate that patients with NIDDM are not capable of maintaining normal plasma FFA concentrations. This defect in FFA metabolism is proportionate to the magnitude of hyperglycemia and occurs despite the presence of elevated levels of plasma insulin. These results are consistent with the view that insulin resistance in NIDDM also involves the ability of insulin to regulate FFA metabolism.

Blood Glucose↗

PubMedDate not supplied

Effect of source of dietary carbohydrate on plasma glucose and insulin responses to mixed meals in subjects with NIDDM.

It has been demonstrated that carbohydrate-rich foods result in different plasma glucose responses when eaten alone by normal subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). This study was designed to test if the glycemic response to mixed meals can be altered by selecting carbohydrate-rich foods based on their glycemic potency. Consequently, three test meals were developed that should have yielded high-, intermediate-, and low-glycemic responses based on the published glycemic index of all the carbohydrate foods in the meals. The test meals were consumed by normal individuals and patients with NIDDM, and the resultant plasma glucose and insulin responses were determined. The results indicated that the plasma glucose responses after the meals did not vary as a function of their glycemic potency in either the normal or NIDDM subjects. There were no significant differences in the plasma insulin responses for either group. These results indicate that the plasma glucose response to mixed meals did not vary as a function of the calculated glycemic potencies. Therefore, the glycemic response to a mixed meal was not predicted on the basis of the published values of the glycemic index of the individual carbohydrate foods included in the meal.

Adult↗