Biomedical subjects

R Bonadonna

Publications and source records attributed to R Bonadonna.

At least 19 recordsLinked to original sources

PubMed1999

Plasma glucose within the normal range is not associated with carotid atherosclerosis: prospective results in subjects with normal glucose tolerance from the Bruneck Study.

OBJECTIVE: There is substantial evidence that glucose intolerance is associated with an increased risk of cardiovascular disease. However, it is not well established whether plasma glucose is independently related to atherosclerosis when glucose tolerance is normal and, if so, to which stage of the complex atherosclerotic process. RESEARCH DESIGN AND METHODS: We prospectively examined the status of carotid arteries in 625 subjects aged 40-79 years who were randomly selected from the general population and had normal glucose tolerance (according to World Health Organization criteria) both at baseline and at 5 years of follow-up. All subjects had high-resolution echo-duplex evaluation of the common and internal carotid arteries (eight regions of interest on both sides) in 1990 and 1995 to detect the change in carotid status over time. The occurrence of new plaques in previously normal segments was termed "incident nonstenotic" or "early atherosclerosis," and the occurrence of stenosis in >40% of previously normal segments was termed "incident stenotic" or "advanced atherosclerosis." In addition, we evaluated the changes in the atherosclerosis score (the sum of all plaques) during the follow-up, and we measured intimal-medial thickening (IMT) in the common carotid artery in 1995. In all subjects, several candidate risk factors were assessed: sex, age, BMI, waist-to-hip ratio, glucose, HbA1c, insulin, urate, lipids, apolipoproteins A1 and B, blood pressure, lipoprotein(a), fibrinogen, antithrombin III, factor V Leiden mutation, ferritin, leukocyte count, smoking, alcohol intake, physical activity, and socioeconomic status. Fasting plasma glucose (FPG), plasma glucose 2 hr after the glucose load (2-h PG), and HbA1c concentrations in 1990 and 1995 were averaged in each subject to obtain an estimate of long-term glucose exposure of the arterial wall. RESULTS: Linear or logistical regression analyses indicated that neither baseline glucose and HbA1c levels nor mean FPG, mean 2-h PG, or mean HbA1c in 1990 and 1995 were independently related to IMT, a 5-year change in the atherosclerotic score, incident nonstenotic (early) atherosclerosis, or incident stenotic (advanced) atherosclerosis. Likewise, subjects with FPG levels above the median and subjects in the new category of "impaired fasting glucose" did not have an increased occurrence or progression of atherosclerosis. All results were consistent before and after adjustment for other vascular risk factors and possible confounders. CONCLUSIONS: These results suggest that plasma glucose levels within the normal range (<7.8 mg/dl both at FPG and 2-h PG) are not independently related to any stage of atherosclerosis.

Adult↗

PubMed1998

U-shaped and J-shaped relationships between serum insulin and coronary heart disease in the general population. The Bruneck Study.

OBJECTIVE: To evaluate the relationship existing between serum insulin and coronary heart disease (CHD) in the general population. RESEARCH DESIGN AND METHODS: In a cross-sectional survey on atherosclerosis and its risk factors, 500 men and 500 women aged 40-79 years were randomly selected from the population of Bruneck, Italy. Clinical, biochemical, and behavioral risk factors of atherosclerosis were assessed in the 936 subjects who participated in the study. Serum insulin was measured at fasting (n = 888) and 2 h (n = 811, known diabetic subjects were excluded) after an oral glucose load. CHD was ascertained by an abnormal electrocardiogram and/or a history of angina or myocardial infarction. RESULTS: Subjects were stratified according to serum insulin quintiles at fasting or 2 h after glucose loading. After adjustment for sex, age, BMI, smoking, physical activity, alcohol intake, and socioeconomic status (analysis of covariance), cardiovascular risk factors clustered in subjects of the top insulin quintile. Multiple logistic regression analysis, including sex and age in model 1, sex, age, BMI, glucose tolerance, socioeconomic status, and behavioral variables in model 2, or this set of variables together with triglycerides and apoproteins A1 and B, fibrinogen, and blood pressure status in model 3, revealed a significant association between high serum insulin and CHD when median insulin quintile was used as the reference class. Moreover, low serum insulin levels, such as those found in subjects of the lowest quintile, were independently related to CHD. These results were found either before (model 1) or after (models 2 and 3) adjusting for several covariates. Consistent results were found in men and women, as well as in younger and older subjects. CONCLUSIONS: Results of the present study suggest that both hyperinsulinemia and "hypoinsulinemia" are independent indicators of CHD. Furthermore, it is proposed that the relationship between CHD and fasting insulin is U-shaped, whereas that between CHD and postglucose insulin may be J-shaped.

Adult↗

PubMed1997

Removal of catheter distortion in multiple indicator dilution studies: a deconvolution-based method and case studies on glucose blood-tissue exchange.

The study of blood-tissue exchange by the multiple indicator dilution technique often needs frequent sampling in the blood of the indicator dilution curves (IDC). Usually, this requires the use of a catheter supported by a pump. This causes a distortion in the IDC, which must be removed for proper interpretation of the data. A deconvolution-based methodology to remove IDC distortion is presented. First, the catheter impulse response is modelled by means of data obtained from a suitable experiment. Then the reconstruction of the blood IDC is tackled by a new nonparametric deconvolution algorithm, which provides (quasi) time-continuous signals and exploits statistically based criteria for the choice of the regularisation parameter. The methodology is applied to the removal of catheter distortion in studies of glucose blood-tissue exchange in the human forearm and myocardium.

Blood Glucose↗

PubMed1997

Relationship between insulin and carotid atherosclerosis in the general population. The Bruneck Study.

BACKGROUND AND PURPOSE: Although several studies have investigated the association between insulin and coronary heart disease, the relationship between this hormone and carotid atherosclerosis is not well established. METHODS: As a part of a population-based survey on atherosclerosis and its risk factors, serum insulin was measured at fasting (n = 888) and at 2 hours after an oral glucose load (n = 811; known diabetic subjects were excluded). The study population comprised an age- and sex-stratified random sample of men and women aged 40 to 79 years. Atherosclerosis in the common and internal carotid arteries was assessed twice (in 1990 and 1995) by duplex sonography. Progression during the 5-years follow-up was defined by an increase in the atherosclerosis score of more than the doubled measurement error (> 27%) or by the occurrence of new plaques. Subjects were stratified in quintiles according to baseline serum insulin at fasting or 2 hours after glucose loading. RESULTS: Logistic regression analysis revealed a significant association of carotid atherosclerosis with both low and high insulin (U-shaped relation). This finding was found before and after adjustment for several covariates (sex, age, body mass index, glucose tolerance, triglycerides, apolipoproteins Al and B, fibrinogen, blood pressure status, behavioral variables, and socioeconomic status). This relation applied equally to fasting and postglucose insulin and was more pronounced in the prospective analysis than in the cross-sectional analysis. CONCLUSIONS: We conclude that both "hypoinsulinemia" and hyperinsulinemia are independent risk indicators of carotid atherosclerosis.

Adult↗

PubMed1997

The experience of therapeutic touch for novice recipients.

This study explored the experience of receiving Therapeutic Touch (TT) from the point of view of recipients with no prior experience with TT. Eleven female graduate students who were part of a larger study were interviewed after the second of two TT sessions and statements from the transcripts were analyzed for words, phrases, or sentences that fell into one of five categories: (a) relaxation, (b) physical sensations, (c) cognitive activity, (d) emotional (feelings), and (e) spiritual/transcendent. All participants reported feeling relaxed and had physical sensations and cognitive activity during the TT sessions, and most of the statements fit into these categories. Fewer statements reflected emotional or spiritual experiences and not all participants had these experiences. The sensations associated with TT may occur developmentally. Initially, physical and cognitive experiences are identified. The deeper, meaningful sensations may occur after an individual has more experience with the intervention.

Adult↗

PubMed1997

Protein metabolism in human obesity: relationship with glucose and lipid metabolism and with visceral adipose tissue.

It is controversial whether metabolic disorders of human obesity include protein metabolism. Even less information is available concerning the effect of fat distribution on protein metabolism. Therefore, a comprehensive evaluation of glucose, lipid, and protein metabolism was performed in 11 obese nondiabetic and 9 normal women whose body composition and regional fat distribution were determined. [1-14C]Leucine and [3-3H]glucose were infused in the postabsorptive state and during an euglycemic hyperinsulinemic (35-40 microU/mL) clamp combined with indirect calorimetry for assessment of leucine flux, oxidation, and nonoxidative disposal, glucose turnover and oxidation, and lipid oxidation. Fat-free mass (FFM) was estimated by a bolus of 3H2O. Subcutaneous abdominal and visceral adipose tissues were determined by nuclear magnetic resonance imaging. During the clamp, obese women had lower glucose turnover (4.51 +/- 0.41 vs. 6.63 +/- 0.40 mg/min.kg FFM; P < 0.05), with a defect in both oxidation (3.27 +/- 0.22 vs. 3.89 +/- 0.21) and nonoxidative disposal (1.24 +/- 0.27 vs. 2.74 +/- 0.41; P < 0.005), whereas lipid oxidation was higher during the clamp (0.49 +/- 0.15 vs. 0.17 +/- 0.09 mg/min.kg FFM). There was no difference in leucine flux (basal, 2.23 +/- 0.17 vs. 2.30 +/- 0.29; clamp, 2.06 +/- 0.19 vs. 2.10 +/- 0.24 mumol/min.kg FFM), oxidation (basal, 0.37 +/- 0.04 vs. 0.36 +/- 0.05; clamp, 0.34 +/- 0.04 vs. 0.39 +/- 0.06) and nonoxidative leucine disposal (basal, 1.86 +/- 0.17 vs. 1.94 +/- 0.26; clamp, 1.72 +/- 0.20 vs. 1.71 +/- 0.19) in the two groups. In obese women, basal leucine oxidation was directly related with glucose oxidation and inversely to lipid oxidation (both P < 0.05), whereas visceral adipose tissue was inversely related to leucine flux both in the basal state and during the clamp (P < 0.05). In conclusion, in human obesity, 1) rates of protein metabolism in the basal state and in the range of insulin concentrations encountered after a meal are normal; 2) protein oxidation is positively related to glucose oxidation and negatively related to lipid oxidation; and 3) visceral adipose tissue is inversely related to all parameters of protein metabolism.

Adipose Tissue↗

PubMed1997

Stress-induced immunosuppression and therapeutic touch.

OBJECTIVE: The specific aim of this study was to evaluate the effectiveness of therapeutic touch in reducing the adverse immunological effects of stress in a sample of highly stressed students. Long-term goals are to develop methods by which a variety of stress-reduction techniques can be tested for efficacy. DESIGN: Experimental. SETTING: A large urban medical university in a southern coastal city. SUBJECTS: Healthy medical and nursing students who are taking professional board examinations. INTERVENTION: Therapeutic touch. MAIN OUTCOME MEASURES: T-lymphocyte function (CD25) and immunoglobulin levels. RESULTS: Subjects who received therapeutic touch and subjects who did not had significantly different levels of IgA and IgM; CD25 (mitogen-stimulated T-lymphocyte function) and IgG levels differed in the expected direction between the two groups, but the differences were not statistically significant. Apoptosis (programmed cell death) was significantly different between the two groups. CONCLUSIONS: The small sample size requires cautious interpretation of the results. This is a pilot study designed to provide evidence to show that further study of therapeutic touch as an intervention that may be useful in reducing the adverse immunologic consequences of anxiety related to stress in otherwise healthy students is warranted. Change in immune function related to anxiety and the relief of anxiety can be measured. Subsequent power analysis suggests sample sizes of 90 subjects per group are required to confirm the conclusions.

Adult↗

PubMed1995

Insulin sensitivity is not impaired in Mexican-American women without a family history of diabetes.

OBJECTIVE: The purpose of this research was to compare insulin sensitivity in Mexican-Americans and non-Hispanic whites without a family history of diabetes to establish whether insulin resistance is a defect intrinsically related to subjects of Mexican origin. RESEARCH DESIGN AND METHODS: In study A, we compared insulin sensitivity in 12 Mexican-American and 12 non-Hispanic white women with normal glucose tolerance and no family history of diabetes. In study B, we compared insulin sensitivity in two groups of normal glucose-tolerant Mexican-Americans, nine with a positive (FHD+) and nine with a negative (FHD-) family history of diabetes. In both studies, the groups were closely matched for age, total body fat content, and fat topography. Insulin sensitivity was assessed with the euglycemic insulin clamp (20 microU.min-1.m2 surface area) which was performed in combination with tritiated glucose infusion and indirect calorimetry. Total fat mass and fat-free mass (FFM) were assessed by a tritiated water dilution technique, and regional fat distribution was evaluated by anthropometry and magnetic resonance imaging. RESULTS: During a 4-h euglycemic insulin clamp (study A), rates (mg.min-1.kg FFM-1) of total (6.32 +/- 0.64 vs. 6.62 +/- 0.81), oxidative (3.54 +/- 0.24 vs. 3.51 +/- 0.19), and nonoxidative (2.78 +/- 0.48 vs. 3.11 +/- 0.75) glucose utilization were similar in Mexican-Americans and non-Hispanic whites; hepatic glucose production (0.33 +/- 0.13 vs. 0.35 +/- 0.13) was suppressed similarly in both groups. During a 2-h euglycemic insulin clamp (study B), Mexican-Americans with FHD+ had lower rates of insulin-mediated total (3.55 +/- 0.39 vs. 5.93 +/- 0.59, P < 0.001), oxidative (3.31 +/- 0.25 vs. 4.32 +/- 0.17, P < 0.01), and nonoxidative (0.24 +/- 0.28 vs. 1.61 +/- 0.49, P < 0.01) glucose disposal than subjects with FHD-; suppression of hepatic glucose production (0.24 +/- 0.14 vs. 0.18 +/- 0.12) was similar in both groups. CONCLUSIONS: These results indicate that in the absence of a family history of non-insulin-dependent diabetes mellitus, Mexican-American women are not less sensitive to insulin than non-Hispanic white women.

Adipose Tissue↗

PubMed1994

Insulin resistance and vasodilation in essential hypertension. Studies with adenosine.

Insulin-mediated vasodilation has been proposed as a determinant of in vivo insulin sensitivity. We tested whether sustained vasodilation with adenosine could overcome the muscle insulin resistance present in mildly overweight patients with essential hypertension. Using the forearm technique, we measured the response to a 40-min local intraarterial infusion of adenosine given under fasting conditions (n = 6) or superimposed on a euglycemic insulin clamp (n = 8). In the fasting state, adenosine-induced vasodilation (forearm blood flow from 2.6 +/- 0.6 to 6.0 +/- 1.2 ml min-1dl-1, P < 0.001) was associated with a 45% rise in muscle oxygen consumption (5.9 +/- 1.0 vs 8.6 +/- 1.7 mumol min-1dl-1, P < 0.05), and a doubling of forearm glucose uptake (0.47 +/- 0.15 to 1.01 +/- 0.28 mumol min-1dl-1, P < 0.05). The latter effect remained significant also when expressed as a ratio to concomitant oxygen balance (0.08 +/- 0.03 vs 0.13 +/- 0.04 mumol mumol-1, P < 0.05), whereas for all other metabolites (lactate, pyruvate, FFA, glycerol, citrate, and beta-hydroxybutyrate) this ratio remained unchanged. During euglycemic hyperinsulinemia, whole-body glucose disposal was stimulated (to 19 +/- 3 mumol min-1kg-1), but forearm blood flow did not increase significantly above baseline (2.9 +/- 0.2 vs 3.1 +/- 0.2 ml min-1dl-1, P = NS). Forearm oxygen balance increased (by 30%, P < 0.05) and forearm glucose uptake rose fourfold (from 0.5 to 2.3 mumol min-1dl-1, P < 0.05). Superimposing an adenosine infusion into one forearm resulted in a 100% increase in blood flow (from 2.9 +/- 0.2 to 6.1 +/- 0.9 ml min-1dl-1, P < 0.001); there was, however, no further stimulation of oxygen or glucose uptake compared with the control forearm. During the clamp, the ratio of glucose to oxygen uptake was similar in the control and in the infused forearms (0.27 +/- 0.11 and 0.23 +/- 0.09, respectively), and was not altered by adenosine (0.31 +/- 0.9 and 0.29 +/- 0.10). We conclude that in insulin-re15-76sistant patients with hypertension, adenosine-induced vasodilation recruits oxidative muscle tissues and exerts a modest, direct metabolic effect to promote muscle glucose uptake in the fasting state. Despite these effects, however, adenosine does not overcome muscle insulin resistance.

Adenosine↗

PubMed1993

Metabolic and hemodynamic effects of insulin on human hearts.

Myocardial muscle is considered to be a target tissue for insulin action, but direct measurements of insulin's effects on cardiac hemodynamics and intermediary metabolism in humans are scarce. We combined great cardiac vein (GCV)/arterial catheterization with the euglycemic insulin clamp technique and thermodilution in six healthy middle-aged (53 +/- 2 yr) volunteers. In the fasting state, the myocardium extracted free fatty acid (FFA), lactate, pyruvate, glycerol, and beta-hydroxybutyrate (6.4 +/- 0.8, 6.2 +/- 1.0, 0.58 +/- 0.12, 0.44 +/- 0.15, and 11 +/- 2 mumol/min, respectively) and consumed 0.26 +/- 0.02 mmol/min oxygen. As fasting plasma insulin (73 +/- 6 pmol/l) was raised and clamped at 503 +/- 16 pmol/l for 100 min while maintaining euglycemia (approximately 5 mmol/l), arterial levels of lactate and pyruvate rose (by 121 and 159%, respectively), whereas FFA, glycerol, and beta-hydroxybutyrate fell (by 69, 48, and 85%, respectively, all P < 0.001). Correspondingly, net myocardial uptake of glucose, lactate, and pyruvate increased to 18.9 +/- 3.5, 32.0 +/- 2.3, and 2.7 +/- 0.5 mumol/min, respectively, whereas net extraction of circulating FFA, glycerol, and beta-hydroxybutyrate was abolished (all P < 0.001). The stimulation of lactate and pyruvate uptake was the result of both increased arterial supply and enhanced myocardial extraction ratio (from 19 +/- 3 to 51 +/- 6% for lactate, from 26 +/- 5 to 44 +/- 5% for pyruvate, P < 0.001 for both). This shift from fat to carbohydrate fuel usage occurred in the absence of changes in oxygen consumption, heart rate, GCV blood flow, aortic pressures, coronary vascular resistance, and left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

PubMed1993

Metabolic and thermogenic effects of lactate infusion in humans.

Lactate has been suggested to interfere with intermediary metabolism by restricting both lipolysis and glucose utilization. To test this hypothesis, in paired studies in healthy volunteers, sodium lactate (25 mumol.min-1 x kg-1) or saline was infused for 1 h in the fasting state and during 2 h of euglycemic (4.75 mM) hyperinsulinemia (approximately 400 pmol/l). Hyperlactatemia (approximately 2 mM) had no inhibitory effect on fasting free fatty acid or glycerol levels nor did it alter the suppressive action of insulin on these substrates. Likewise, sodium lactate infusion did not influence hepatic glucose production ([3-3H]glucose technique) or its suppression by insulin. During the clamp, hyperlactatemia was associated with a small increase in whole body glucose disposal (34.9 +/- 4.1 vs. 30.3 +/- 3.7 mumol.min-1 x kg-1, P < 0.05) with no major change in the pattern of substrate (carbohydrate vs. lipid) oxidation. By simultaneously measuring arteriovenous gradients across the deep tissues of the forearm (forearm technique), it was found that hyperlactatemia did not impede insulin-mediated glucose uptake; furthermore, it could be estimated that muscle tissues were responsible for the disposal of roughly one-fifth of the lactate load. Whole body energy expenditure was stimulated above the level achieved with hyperinsulinemia when lactate was also infused. Thus, under the present experimental conditions, physiological hyperlactatemia did not interfere with lipolysis, hepatic glucose production, or whole body or forearm muscle glucose utilization, or with insulin action on these processes, and was accompanied by a strong thermogenic effect.

Adult↗

PubMed1993

The touching goes both ways.

Explore the source record for details and available documents.

Adult↗

PubMed1992

Therapeutic touch and post-Hurricane Hugo stress.

This repeated-session design sought to answer questions about the effectiveness of therapeutic touch in reduction of stress for 23 individuals following a natural disaster. In addition, methodological issues related to the average length of time for a therapeutic-touch treatment and a method of documenting the nonverbal interaction between subject and toucher were investigated. Findings indicate that stressed people report themselves to be less stressed following therapeutic touch (p = .05). Time of therapeutic-touch intervention varied significantly between the touchers, with a range of 6.8 to 20 minutes. Qualitative data examining the interaction of toucher and subject raised a number of questions that require further study.

Adolescent↗

PubMed1990

Effect of prolonged overnight fasting on energy metabolism in non-insulin-dependent diabetic and non-diabetic subjects.

The effect on energy metabolism of a 6-h prolongation of the conventional 12-h overnight fast was examined in 9 healthy subjects and in 7 patients with non-insulin-dependent diabetes mellitus. Plasma glucose concentration decreased by 7 and 23%, in control and diabetic subjects, respectively. In control subjects, the fall in plasma glucose was associated with a slight but significant fall in plasma insulin and a rise in plasma free fatty acid concentrations. During this same period, the rates of plasma free fatty acid oxidation, measured by infusion of [14C]palmitate, and net lipid oxidation, measured by indirect calorimetry, increased in normal subjects by 55 and 76%, respectively; the rate of glucose oxidation measured by indirect calorimetry decreased by 37%. In the diabetic patients, the free fatty acid oxidation rate was enhanced already after 12 h of fasting compared with controls (2.06 vs 1.30 mumol.kg-1.min-1; p less than 0.05) and did not change significantly during the 6-h observation period. After 18 h of fasting, the rate of plasma free fatty acid oxidation was similar in control and diabetic subjects. The data thus emphasize the need for strict standardization of the overnight fasting period for metabolic studies, and demonstrate the difficulties in comparing basal rates of substrate oxidation between healthy and diabetic subjects.

Adult↗

PubMed1990

Operation of Randle's cycle in patients with NIDDM.

It has been suggested that the insulin resistance of non-insulin-dependent diabetes mellitus (NIDDM) may be caused by substrate competition between glucose and free fatty acids (FFAs) (Randle's cycle). We measured substrate oxidation and energy metabolism in 10 nonobese untreated NIDDM patients with fasting glucose levels of 7-8 mM with indirect calorimetry in the basal state and during an isoglycemic-hyperinsulinemic (approximately 100 mU/L) clamp without (control) and with a concomitant infusion (approximately 0.35 mmol/min) of Intralipid, a triglyceride emulsion. In the control study, fasting rates of total glucose turnover [( 3-3H]glucose) and glucose and lipid oxidation (9.4 +/- 1.4, 7.3 +/- 1.3, and 3.0 +/- 0.4 mumol.kg-1.min-1, respectively) were comparable with those of nondiabetic individuals. After insulin administration, lipid oxidation was normally suppressed (to 1.3 +/- 0.3 mumol.kg-1.min-1, P less than 0.01), as were the circulating levels of FFA, glycerol, and beta-hydroxybutyrate, whereas glucose oxidation doubled (14.1 +/- 1.8 mumol.kg-1.min-1, P less than 0.01). Because glycemia was clamped at 7.5 mM, endogenous glucose production (EGP) was completely suppressed, and total glucose disposal was stimulated (to 25.7 +/- 5.2 mumol.kg-1.min-1, P less than 0.01 vs. baseline), but glucose clearance (3.6 +/- 0.8 ml.kg-1.min-1) was 30% reduced compared with normal. With concomitant lipid infusion, FFA, glycerol, and beta-hydroxybutyrate all rose during the clamp; correspondingly, lipid oxidation was maintained at fasting rates (3.6 +/- 0.2 mumol.kg-1.min-1, P less than 0.01 vs. control).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

PubMed1989

A compartmental model to quantitate in vivo glucose transport in the human forearm.

Glucose transport is a critical step in the control of glucose disposal that, until presently, has not been quantitated in vivo in humans. We have employed the perfused forearm and euglycemic insulin-clamp techniques in combination with a dual-tracer injection to measure basal and insulin-mediated glucose transport in six normal subjects. L-[3H]glucose, which is not transported, was used to trace extracellular glucose kinetics; 3-O-[14C]-methyl-D-glucose, transportable but not metabolizable, was used to monitor glucose movement across the cell membrane. After bolus intra-arterial injection of the two tracers, plasma samples were obtained every 15-30 s for 10 min from a deep forearm vein to determine the washout curves. A linear compartmental model was developed that accounts for blood flow heterogeneity. It consists of three parallel, two-compartment chains merging into the sampling compartment to which cellular compartments are appended. A priori identifiability analysis was performed. The uniquely identifiable parameterization includes the transport rate constants of glucose into and out of the cell. The model was identified using nonlinear least-squares parameter estimation. Transport parameters are estimated with very good precision, and their reproducibility is satisfactory. The model also allows the estimation of the mean arteriovenous transit times of both the extracellular and the transported tracer. The compartmental model provides a novel approach to investigate glucose transport in vivo in humans.

3-O-Methylglucose↗

PubMed1988

Platelet and clotting activities after cold stress in diabetic patients.

Platelet and clotting abnormalities have been described in diabetes, but little is known about their relationship to daily stresses. In order to evaluate whether states of abnormal carbohydrate metabolism modify the hemostatic response to stress, 12 subjects with type I diabetes mellitus, 9 with type II, 7 with impaired glucose tolerance and 10 healthy controls were exposed to a cold pressor test. Plasma concentrations of beta-thromboglobulin (index of platelet activation) and of fibrinopeptide A (index of thrombin formation) were measured before and 15 minutes after forearm immersion in melting ice. Basal levels of both proteins were significantly elevated (p less than 0.02) in the combined group of patients with diabetes and impaired glucose tolerance. While in healthy controls cold exposure failed to modify plasma concentration of either protein, obvious changes occurred in the diabetic and impaired glucose tolerance groups. In the combined patients group, beta-thromboglobulin levels decreased from 1.37 +/- 0.44 nmol/l to 1.03 +/- 0.39 (mean +/- SD, p less than 0.01), after the cold test, possibly in consequence of enhanced vascular permeability; while fibrinopeptide A levels increased from 1.52 +/- 1.03 nmol/l to 3.45 +/- 4.19 (p less than 0.02). The degree and pattern of abnormalities observed in basal as well as stimulated levels of fibrinopeptide A differed somewhat among the three groups of patients. These studies indicate that, in the basal state, patients with diabetes or simple carbohydrate intolerance are more susceptible than controls to platelet activation and that after stress thrombin formation can occur although some variability exists among and within groups of patients. The consequences of such increased thrombotic activity may have a bearing on the pathogenesis of large vessel disease, a complication common to diabetes and impaired glucose tolerance.

Blood Coagulation↗

PubMed1987

Insulin resistance in essential hypertension.

High blood pressure is prevalent in obesity and in diabetes, both conditions with insulin resistance. To test whether hypertension is associated with insulin resistance independently of obesity and glucose intolerance, we measured insulin sensitivity (using the euglycemic insulin-clamp technique), glucose turnover (using [3H]glucose isotope dilution), and whole-body glucose oxidation (using indirect calorimetry) in 13 young subjects (38 +/- 2 years [+/- SEM]) with untreated essential hypertension (165 +/- 6/112 +/- 3 mm Hg), normal body weight, and normal glucose tolerance. In the postabsorptive state, all measures of glucose metabolism were normal. During steady-state euglycemic hyperinsulinemia (about 60 microU per milliliter), hepatic glucose production and lipolysis were effectively suppressed, and glucose oxidation and potassium disposal were normally stimulated. However, total insulin-induced glucose uptake was markedly impaired (3.80 +/- 0.32 vs. 6.31 +/- 0.42 mg per minute per kilogram of body weight in 11 age- and weight-matched controls, P less than 0.001). Thus, reduced nonoxidative glucose disposal (glycogen synthesis and glycolysis) accounted for virtually all the defect in overall glucose uptake (1.19 +/- 0.24 vs. 3.34 +/- 0.44 mg per minute per kilogram, P less than 0.001). Total glucose uptake was inversely related to systolic or mean blood pressure (r = 0.76 for both, P less than 0.001). These results provide preliminary evidence that essential hypertension is an insulin-resistant state. We conclude that this insulin resistance involves glucose but not lipid or potassium metabolism, is located in peripheral tissues but not the liver, is limited to nonoxidative pathways of intracellular glucose disposal, and is directly correlated with the severity of hypertension.

Adult↗