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Biomedical subjects

M S Greenfield

Publications and source records attributed to M S Greenfield.

18 recordsLinked to original sources
PubMed1994

Changes in glucose, insulin, lipid, lipoprotein, and apoprotein concentrations and insulin action in doxazosin-treated patients with hypertension. Comparison between nondiabetic individuals and patients with non-insulin-dependent diabetes mellitus.

Thirty patients with hypertension were enrolled in this study, 13 had non-insulin-dependent diabetes mellitus (NIDDM) and 17 were nondiabetic. Patients were treated with doxazosin for approximately 4 months, and blood pressure fell significantly (P < .001) in both nondiabetics (149/96 to 134/85 mm Hg) and in those with NIDDM (154/96 to 143/84 mm Hg). In the nondiabetic group, doxazosin treatment was associated with significant improvement in insulin-mediated glucose disposal (P < .05) and lower plasma insulin (P < .001), and triglyceride (P < .001) concentrations measured at hourly intervals from 8 AM to 4 PM (breakfast at 8 AM and lunch at noon). In addition, fasting total plasma (P < .001) and VLDL cholesterol (P < .01), and total plasma (P < .05), VLDL (P < .08), LDL (P < .01), HDL (P < .01) triglyceride concentrations were lower following doxazosin treatments in the nondiabetic group, as was the ratio of total to HDL cholesterol (P < .001). Finally, apoprotein B concentrations fell with doxazosin in the nondiabetic group (P < .01). Significant changes seen in the group with NIDDM included a decrease in the ratio of total to HDL cholesterol (P < .001) and a fall in apoprotein B concentration (P < .05). However, values for all other variables did not change significantly with treatment in this group. Thus, doxazosin treatment of nondiabetic subjects with high blood pressure was associated with a series of changes in glucose, insulin, and lipoprotein metabolism that should decrease risk of coronary heart disease (CHD) in these individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗
PubMed1994

Additive effects of obesity, hypertension, and type 2 diabetes on insulin resistance.

Resistance to insulin-mediated glucose disposal has been previously shown to be increased in association with obesity, high blood pressure, and non-insulin-dependent diabetes mellitus. We initiated the present study to quantify the separate effects of hypertension and non-insulin-dependent diabetes mellitus on insulin resistance in both nonobese and obese subjects. To accomplish this, 88 subjects were divided into the following five experimental groups: normal blood pressure, nonobese (n = 17); normal blood pressure, obese (n = 18); high blood pressure, nonobese (n = 18); high blood pressure, obese (n = 19); and high blood pressure, obese, non-insulin-dependent diabetes mellitus (n = 16). Plasma glucose and insulin concentrations were measured before and after a 75-g oral glucose load. Resistance to insulin-mediated glucose disposal was estimated by determining the steady-state plasma insulin and glucose concentrations during the last 30 minutes of a continuous infusion of somatostatin (5 micrograms/min), exogenous insulin (25 mU/m2 per minute), and glucose (240 mg/m2 per minute). Since the steady-state plasma insulin concentrations are similar in all subjects, the higher the steady-state plasma glucose, the more insulin resistant the individual. Nonobese subjects with normal blood pressure had the lowest plasma glucose and insulin responses and steady-state plasma glucose concentrations, and their values were significantly different from the other four groups. Obese or nonobese subjects with high blood pressure had significantly higher plasma glucose responses and steady-state plasma glucose concentrations than did their respective weight-matched control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1990

Effect of acarbose on carbohydrate and lipid metabolism in NIDDM patients poorly controlled by sulfonylureas.

The ability of acarbose to lower plasma glucose concentration was studied in 12 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were poorly controlled by diet plus sulfonylurea drugs. Patients were studied before and 3 mo after the addition of acarbose to their treatment program, and a significant improvement in glycemic control was noted. Although the decrease in fasting plasma glucose concentration was modest (12.0 +/- 0.8 to 10.8 +/- 0.3 mM), average postprandial plasma glucose concentration decreased by 3.4 mM. When acarbose therapy was discontinued in 5 patients, plasma glucose levels rapidly returned toward pretreatment levels. In addition to the improvement in glycemia, acarbose treatment also led to a significant reduction in HbA1c (7.4 +/- 0.2 to 6.4 +/- 0.2%, P less than 0.01) and triglyceride (2.4 +/- 0.1 to 2.1 +/- 0.1 mM, P less than 0.01) concentrations. Neither the plasma insulin response to meals nor insulin-stimulated glucose uptake improved with acarbose therapy, consistent with the view that acarbose improves glycemic control by delaying glucose absorption. Considerable individual variation was noted in the response to acarbose, and the results in 4 patients were dramatic, with striking reductions in both fasting and postprandial glucose concentrations. The addition of acarbose to patients with NIDDM not well controlled by sulfonylureas appears to have significant clinical benefit.

Acarbose↗
PubMed1986

Reduced plasma high density lipoprotein-cholesterol concentrations need not increase when hyperglycemia is controlled with insulin in noninsulin-dependent diabetes mellitus.

The ability of intensive insulin treatment to increase plasma high density lipoprotein (HDL)-cholesterol levels was evaluated in 12 patients with noninsulin-dependent diabetes mellitus. Patients were treated for 6 weeks with one daily morning injection of ultralente insulin, in combination with administration of regular insulin before breakfast, lunch, and dinner. The mean (+/- SEM) fasting plasma glucose concentration fell from 289 +/- 21 to 122 +/- 9 mg/dl (P less than 0.001), and the mean hourly postprandial glucose concentration fell from 313 +/- 24 to 102 +/- 7 mg/dl (P less than 0.001). In addition, insulin treatment was associated with a reduction in both fasting plasma triglyceride (256 +/- 45 to 137 +/- 18 mg/dl; P less than 0.001) and cholesterol (224 +/- 25 to 199 +/- 19 mg/dl; P less than 0.05) concentrations. However, plasma HDL-cholesterol concentrations, which were low to begin with, did not rise in association with excellent glycemic control. These results demonstrate that hyperglycemia and hypertriglyceridemia can be effectively reduced by an aggressive program of insulin treatment in patients with noninsulin-dependent diabetes mellitus, but this intervention need not lead to an improvement in the abnormal HDL-cholesterol metabolism in these patients.

Adult↗
PubMed1984

Acarbose treatment of non-insulin-dependent diabetes mellitus.

Acarbose is a newly developed inhibitor of intestinal alpha-glucosidase, and in the current study its ability to lower plasma glucose levels was studied in 12 patients with non-insulin-dependent diabetes mellitus, poorly controlled on diet plus sulfonylurea drugs. Patients were studied before and three months after the addition of acarbose to their treatment program, and there was a notable fall in postprandial plasma glucose concentrations that approximated 60 mg/dL. When acarbose therapy was discontinued in five patients, plasma glucose levels rapidly returned toward pretreatment levels. In addition to the improvement in glycemia, acarbose treatment also led to a notable reduction in Hb A1c and triglyceride concentrations. Finally, considerable individual variation was noted in the response to acarbose, and the results in four patients were quite dramatic, with striking reductions in both fasting and postprandial glucose concentrations. These data suggest that acarbose may be a useful addition in the treatment of patients with non-insulin-dependent diabetes mellitus.

Acarbose↗
PubMed1983

Insulin secretion and action in noninsulin-dependent diabetes mellitus. Is insulin resistance secondary to hypoinsulinemia?

The insulin-stimulated glucose metabolic clearance rate, assessed by the insulin clamp technique, was compared in 40 normal subjects and 40 age- and weight-matched patients with noninsulin-dependent diabetes mellitus. These studies were conducted at steady-state plasma insulin levels of approximately 100 microU/ml, and the mean (+/- standard error of the mean) glucose metabolic clearance rate of patients with noninsulin-dependent diabetes mellitus was 81 +/- 9 ml/m2 per minute, as compared with a value of 235 +/- 14 ml/m2 per minute for normal subjects. This difference was highly statistically significant (p less than 0.001) and documents the extreme resistance to insulin-stimulated glucose utilization seen in noninsulin-dependent diabetes mellitus. Patients with noninsulin-dependent diabetes mellitus were also shown to have a lower than normal plasma insulin response to an oral glucose challenge. In contrast, ambient plasma insulin concentrations of normal subjects and patients with noninsulin-dependent diabetes mellitus were found to be quite comparable when measured throughout the day in response to the ingestion of conventional mixed meals. Consequently, absolute hypoinsulinemia is not characteristic of patients with noninsulin-dependent diabetes mellitus under conditions of daily living. Finally, the ability of intensive insulin treatment to improve insulin resistance was studied after one and six weeks of therapy. These results indicated that successful control of hyperglycemia led to a significant improvement in insulin action as early as one week after the initiation of insulin therapy, with no further changes noted after prolonged insulin administration. The degree to which insulin action approached normal values was greater when studies were carried out at circulating insulin levels of approximately 2,000 microU/ml as compared with insulin levels of approximately 100 microU/ml, but in both instances insulin-treated diabetic patients remained insulin-resistant as compared with normal subjects. These results have corroborated the fact that abnormalities of both insulin action and secretion can be documented in patients with noninsulin-dependent diabetes mellitus. However, patients with noninsulin-dependent diabetes mellitus were not found to be absolutely hypoinsulinemic in their daily existence, and control of their hyperglycemia with exogenous insulin did not restore insulin-stimulated glucose utilization to normal. Consequently, these data are not consistent with the view that the insulin resistance in noninsulin-dependent diabetes mellitus is entirely a secondary consequence of the hypoinsulinemia presumed to be present in these patients.

Adult↗
PubMed1983

Studies of diabetic polyneuropathy using conduction velocity distribution (DCV) analysis.

The distributions of nerve fiber conduction velocities (DCVs) derived from the median nerves of 29 adult diabetic patients (mean age, 52.1 +/- 12.3 years) with mild or no symptoms or signs of polyneuropathy were compared with DCVs from 34 age-appropriate normal subjects. Ten patients (34%) had normal findings (type A DCVs). In the 19 patients (66%) with abnormal DCVs, defined as 10% or more of the DCV area falling outside the normal 95% confidence limits, two distinct patterns of DCV alteration were observed: type B DCVs (11 patients) showed reduced DCVmax, DCVmean, and DCVpeak, together with reduced DCVrange (narrow profile); whereas type C DCVs (8 patients) had reduced DCVmax, DCVmean, DCVpeak, and DCVmin, with normal DCVrange (broad profile). It is proposed that type C DCV represents a more advanced form of type B and that both reflect selective dysfunction of the fastest conducting (presumably largest-diameter) fibers in the nerve trunk. DCVmax was consistently greater than conventional measures of "maximal" CV in all patient subgroups. Patients with abnormal DCVs had higher incidence of mild neuropathic symptoms (15 of 19 versus 4 of 10, p less than 0.01) and greater insulin dependence (11 of 19 versus 1 of 10, p less than 0.001). Serial studies in 10 patients showed, at most, small degrees of change in conduction properties over relatively short intervals (1 to 9 months).

Action Potentials↗
PubMed1982

Effect of sulfonylurea treatment on in vivo insulin secretion and action in patients with non-insulin-dependent diabetes mellitus.

The effect of glipizide treatment on diabetic control and on in vivo insulin secretion and action was studied in 20 patients with non-insulin-dependent diabetes mellitus (NIDDM). Patients were examined before and after a minimum of 3 mo treatment. Mean (+/- SEM) fasting plasma glucose level fell from 264 +/- 12 mg/dl to 172 +/- 10 mg/dl (P < 0.001) after glipizide treatment, and this was associated with a fall in total plasma glucose response to a test meal of approximately 35%. Mean (+/- SEM) fasting plasma insulin levels increased slightly from 15 +/- 2 micronU/ml following sulfonylurea treatment, and the total plasma insulin response to the test meal increased by 63%. However, there was no correlation (r = - 0.20) between the increase in plasma insulin response and the fall in plasma glucose levels that occurred as the result of sulfonylurea therapy. Glipizide treatment also led to enhanced in vivo insulin action, whether measured by the insulin clamp technique (P < 0.001) or the insulin suppression test (P< 0.02). Furthermore, in this instance there was a significant correlation (r - 0.69, P < 0.001) between the enhanced insulin action and the improvement on diabetes control. Thus, chronic therapy with glipizide, a new sulfonylurea agent, led to increased in vivo insulin secretion and insulin action. These results lend direct support to the assumption that sulfonylurea compounds have a substantial extrapancreatic effect on glucose homeostasis, and suggest that this effect contributes to the therapeutic efficacy of these drugs.

Aged↗
PubMed1982

Comparison of insulin secretion and in vivo insulin action in nonobese and moderately obese individuals with non-insulin-dependent diabetes mellitus.

Insulin secretion and in vivo insulin action were quantified in nonobese and moderately obese patients (approximately 30% overweight) with non-insulin-dependent diabetes mellitus (NIDDM), matched for severity of diabetes. Insulin secretion was assessed by determining plasma insulin responses to a test meal given at noon, and in vivo insulin action by the insulin clamp technique. No significant differences were noted between the two groups for either variable. Thus, it cannot be assumed that the cause of hyperglycemia in patients with NIDDM differs between nonobese and moderately obese subjects.

Blood Glucose↗
PubMed1982

Effect of variations in basal plasma glucose concentration on glucose utilization (M) and metabolic clearance (MCR) rates during insulin clamp studies in patients with non-insulin-dependent diabetes mellitus.

Two insulin clamp studies were performed at different steady-state plasma glucose concentrations in 13 patients with non-insulin-dependent diabetes mellitus (NIDDM). Steady-state plasma insulin concentrations were comparable, with mean +/- SEM levels of 94 +/- 3 and 95 +/- 4 muU/ml being achieved during the two studies. Glucose utilization rate (M) varied directly with plasma glucose concentration in each subject. Thus, the mean +/- SEM value of M was 4.92 +/- 0.73 mg/kg/min when patients were studied at a mean +/- SEM plasma glucose concentration of 226 +/- 15 mg/dl, and M was 2.71 mg/kg/min when the same subjects were studied at a glucose concentration of 118 +/- 6 mg/dl. In contrast, the values for glucose metabolic clearance rate (MCR), which were 2.35 +/- 0.50 and 2.49 +/- 0.47 ml/kg/min, respectively, during the two studies, did not vary significantly with plasma glucose concentration. These data indicate that the glucose metabolic clearance rate (MCR), but not glucose utilization rate (M), can be used to compare in vivo insulin action when insulin clamp studies are performed in subjects with different basal plasma glucose concentrations.

Blood Glucose↗
PubMed1982

Does insulin removal rate from plasma decline with age?

The effect of age on the rate of insulin removal from plasma was studied in both rat and man. The experimental approach was based on measurement of the steady-state plasma insulin concentration achieved during a period in which endogenous insulin secretion was suppressed and exogenous insulin infused. Rats, 1 1/2 and 12 mo of age, were infused with 2.5, 5.0, and 10.0 mU/kg of insulin during a 180-min period in which endogenous insulin secretion was suppressed by epinephrine and propranolol. Steady-state plasma insulin concentrations were approximately twice as high in the older rats at every insulin infusion rate. Similar results were seen in man; significant correlations were observed between height of steady-state plasma insulin concentration and advancing age during infusion of exogenous insulin and suppression of endogenous insulin with either exogenous insulin (r = 0.66, P less than 0.001) or epinephrine and propranolol (r = 0.47, P less than 0.01). Since infusion rates of exogenous insulin were identical in all studies, these results suggest that there is an age-related decrease in insulin catabolism.

Adult↗
PubMed1982

Lipid metabolism in non-insulin-dependent diabetes mellitus: effect of glipizide therapy.

Plasma lipid concentration and lipoprotein composition were studied before and after several months of glipizide treatment in 23 patients with non-insulin-dependent diabetes mellitus. The mean (+/- SEM) plasma glucose level fell 87 mg/dL, and the fall in plasma glucose concentration was correlated with a reduction in plasma triglyceride, very low-density lipoprotein triglyceride, cholesterol, and low-density lipoprotein cholesterol levels. Furthermore, there was a statistically significant increase in the plasma high-density lipoprotein cholesterol to total cholesterol ratio. Thus, improved diabetic control in patients treated with glipizide with non-insulin-dependent diabetes mellitus leads to changes in lipoprotein metabolism thought to be beneficial in terms of known cardiovascular risk factors.

Aged↗
PubMed1981

Effect of differences in source of dietary carbohydrate on plasma glucose and insulin responses to meals in patients with impaired carbohydrate tolerance.

Two test meals, varying only in type of carbohydrate foods, were given to 12 volunteers with impaired glucose tolerance. The carbohydrate content of one meal was composed of potato and gelatin, while the other meals contained an equivalent amount of carbohydrate as rice and corn. The two meals were otherwise identical, and the additional constituents were turkey, green salad, and salad dressing. Plasma glucose and insulin responses were significantly lower after the meal containing rice and corn, with the change in the insulin response being the most dramatic. These results raise the possibility that variations in source of dietary carbohydrate may have therapeutic utility in patients with impaired glucose tolerance.

Adult↗
PubMed1981

The impact of autonomic nervous system dysfunction on breathing during sleep.

Ten patients with autonomic nervous system dysfunction (familial dysautonomia, juvenile diabetes, or Shy-Drager syndrome) were studied to assess the impact of their impairment on breathing during sleep. Several types of breathing dysfunction during sleep were identified independent of the patients' primary complaints. Obstructive sleep apnea syndrome was the most common; central sleep apnea and disturbances of te respiratory oscillator also were seen. Esophageal reflux was found to be the cause of some sleep-related problems. The observed respiratory irregularities were not associated with the usual cardiac response; a "decoupling" of heart rate from the respiratory cycle was noted during sleep in these patients.

Adolescent↗
PubMed1981

Diabetic hypertriglyceridemia: evidence for three clinical syndromes.

Based on studies of both man and rat, it is proposed that at least three distinct syndromes of hypertriglyceridemia occur as the result of abnormalities of carbohydrate metabolism. We believe that these syndromes are the predictable results of the changes in plasma insulin and/or free fatty acid (FFA) concentration that occur in patients with impaired glucose tolerance (IGT), non-insulin-dependent diabetes mellitus (NIDDM), and insulin-dependent diabetes mellitus (IDDM). In patients with IGT the basic defect is postulated to be loss of normal insulin sensitivity, leading to compensatory hyperinsulinism, increased very low density lipoprotein (VLDL)-triglyceride (TG) secretion, and hypertriglyceridemia. In contrast, patients with NIDDM have ambient insulin concentrations that are "normal" in absolute terms, and in these subjects we believe that the elevated circulating FFA concentrations increase hepatic VLDL-TG secretion, which, in turn, is responsible for the hypertriglyceridemia. However, elevated FFA levels do not stimulate hepatic VLDL-TG secretion in insulin-deficient patients with IDDM, presumably because the livers of such individuals are not capable of responding to the increased FFA flux. In these subjects, the development of hypertriglyceridemia, when it does occur, is secondary to the existence of a profound defect in the removal of VLDL-TG from plasma. These generalizations are consistent with results in both man and rat, and provide models that account for the development of hypertriglyceridemia in the three major clinical categories of abnormal carbohydrate metabolism.

Animals↗
PubMed1981

Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp.

Insulin resistance was quantified with two different methods in 30 subjects with varying degrees of glucose tolerance. One method, the insulin suppression test, is performed by continuously infusing epinephrine, propranolol, insulin, and glucose. Epinephrine and propranolol suppress endogenous insulin release, and steady-state plasma levels of exogenous insulin and glucose are reached in all individuals. Because the steady-state insulin level is the same in all subjects, the height of the steady-state plasma glucose level provides a direct estimate of insulin resistance. The other method, the euglycemic clamp technique, produces a steady-state level of exogenous hyperinsulinemia by means of a primed and continuous insulin infusion. Glucose is also infused at a rate sufficient to prevent an insulin-induced fall in glucose concentration, and the amount of glucose required to maintain the basal plasma glucose level provides the estimates of insulin resistance. The results indicated that estimates of insulin resistance generated by the two methods were highly correlated (r = 0.93). Furthermore, both methods of assessing insulin resistance indicated that the greater the degree of glucose intolerance, the more severe the insulin resistance. These results serve to further emphasize the importance of insulin resistance in the pathogenesis of hyperglycemia in type II diabetes.

Adult↗
PubMed1980

Effect of age on plasma triglyceride concentrations in man.

Plasma triglyceride (TG) concentrations increase with advancing age. To determine if this phenomenon is due to age per se or to age-related changes in other metabolic variables, determination of fasting plasma TG, glucose, insulin, and free fatty acid (FFA) concentrations, as well as body mass index (BMI), were made on 167 normal subjects from 18 to 77 yr of age. Significant simple correlation coefficients (r) were found between TG concentrations and age (0.47), BMI (0.39) and fasting plasma glucose (0.40), insulin (0.24), and FFA (0.20) concentrations. Multiple regression analysis was used to determine the total amount of variability in TG concentration that could be accounted for by the combination of the examined metabolic parameters. A highly significant (p < 0.0001) total correlation of 0.57 was obtained, indicating that these variables could account for approximately one-third of the total variances. Partial correlation analysis (fixing four of the five variables) yielded a correlation coefficient of 0.35 (p < 0.001) between age and fasting TG concentration. Hence, age per se, or an age-dependent phenomenon, appears to be an independent factor with a role in determining plasma TG concentrations.

Adolescent↗