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Biomedical subjects

G Reaven

Publications and source records attributed to G Reaven.

At least 19 recordsLinked to original sources
PubMed2001

Metabolic abnormalities characteristic of dysmetabolic syndrome predict the development of transplant coronary artery disease: a prospective study.

BACKGROUND: This study examines the hypothesis that metabolic abnormalities of dysmetabolic syndrome are risk factors for transplant coronary artery disease (TxCAD). METHODS AND RESULTS: Sixty-six patients without overt diabetes, 2 to 4 years after surgery, underwent intracoronary ultrasound (ICUS), measurement of plasma glucose and insulin after oral glucose (75 g), and fasting lipid and lipoproteins. TxCAD incidence by angiography or autopsy was prospectively determined during subsequent follow-up (8 years). Coronary artery intimal thickness (IT) and subsequent outcomes were compared in patients stratified as having "high" versus "low" plasma glucose (>8.9 mmol/L) and insulin (>760 pmol/L) 2 hours after glucose challenge; and "abnormal" versus "normal" fasting lipid and lipoprotein concentrations as defined by the National Cholesterol Education PROGRAM: Patients with high glucose or insulin concentrations had greater IT: 0.38+/-0.05 versus 0.22+/-0.02 mm, P</=0.05, and 0.39+/-0.05 versus 0.20+/-0.02 mm, P</=0.01, respectively. Freedom from TxCAD was 56+/-11% versus 81+/-6% (P<0.01) in patients with high versus low glucose and 57+/-10% versus 82+/-7% (P<0.05) in patients with high versus low insulin. Actuarial survival was 60+/-12% versus 92+/-5% (P<0.005) in patients with high versus low glucose and 72+/-9% versus 88+/-6% (P<0.05) in patients with high versus low insulin. Triglycerides and VLDL were higher and HDL was lower in patients with IT >0.3 mm than with IT </=0.3 mm. TxCAD incidence was higher in patients with high plasma TG and VLDL and low HDL. CONCLUSIONS: These data suggest that insulin resistance plays a role in TXCAD:

Adult↗
PubMed2001

Effect of orlistat-assisted weight loss in decreasing coronary heart disease risk in patients with syndrome X.

This study describes the changes in risk factors for coronary heart disease in obese persons with syndrome X after orlistat-assisted weight loss. Data were available for 1,700 patients who completed 52 weeks of weight loss; 128 were defined as having syndrome X by being in the quintile with the highest plasma triglyceride levels (>2.2 mM/L) and the lowest high-density lipoprotein cholesterol (HDL, <1.0 mM/L) concentrations. Initial characteristics of those with syndrome X were similar to the 119 subjects (non-syndrome X) in the lowest quintile of plasma triglyceride (<0.975 mM/L) and highest quintile of HDL cholesterol (>1.5 mM/L). Subjects were placed on a calorie-restricted diet, and randomized to receive orlistat or placebo. Initial values were higher in those with syndrome X for diastolic blood pressure (p = 0.03), plasma insulin (p = 0.0001), triglyceride (p = 0.0001) concentrations, and ratio of low-density lipoprotein cholesterol to HDL cholesterol (p = 0.0001), and were lower for HDL cholesterol (p = 0.001) concentrations. Weight loss was greater in both groups of orlistat-treated patients (p = 0.026); in those with syndrome X, it was associated with a significant reduction in plasma insulin (p = 0.019) and triglyceride (p = 0.0001) concentrations, an increase in HDL cholesterol concentration, and a decrease in low-density lipoprotein/HDL cholesterol ratio (p = 0.0001). There were no significant changes in plasma insulin, triglycerides, or HDL cholesterol concentration in the non-syndrome X group. In conclusion, weight loss attenuates coronary heart disease risk factors in obese persons with syndrome X, and the risk factor reduction is enhanced with administration of orlistat.

Adult↗
PubMed2001

Relationship between insulin resistance, weight loss, and coronary heart disease risk in healthy, obese women.

Several popular books have recently been published stating that being insulin-resistant favors weight gain and/or prevents weight loss. Because this view seems to have gained widespread support in the general population, we thought it important to perform the current study testing the hypothesis that differences in insulin-mediated glucose disposal do not affect weight loss in response to calorie-restricted diets. For this purpose, we studied the change in weight and risk factors for coronary heart disease (CHD) in healthy women volunteers, defined as being obese on the basis of a body mass index (BMI) greater than 30.0 kg/m(2). The insulin suppression test was used to stratify obese women at baseline into insulin-resistant and insulin-sensitive subgroups on the basis of their steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of octreotide, exogenous insulin, and glucose. They were then instructed on a calorie-restricted diet plus sibutraminine (15 mg/day) for a total period of 4 months. Baseline measurements also included determination of fasting lipid and lipoprotein concentrations, and hourly (8 AM to 4 PM) determinations of plasma glucose and insulin concentrations before and after breakfast and lunch. Twenty-four women completed the 4-month period of calorie restriction: 13 classified as insulin-resistant (SSPG = 219 +/- 7 mg/dL) and 11 as insulin-sensitive (SSPG = 69 +/- 6 mg/dL). The insulin-resistant group also had higher (P =.03) plasma triglyceride (TG) concentrations and a higher ratio of total to high-density lipoprotein (HDL) cholesterol concentration (P =.02) at baseline. Both groups lost a significant amount of weight during the study, and there was no difference between the weight loss in the insulin-resistant (8.6 +/- 1.3 kg) and insulin-sensitive (7.9 +/- 1.4 kg) groups. Weight loss in the insulin-resistant group was also associated with a significant decrease in SSPG concentration (219 +/- 7 to 144 +/- 14 mg/dL), associated with significantly lower fasting TG concentrations (P <.001) and day-long concentrations of plasma glucose and insulin (P <.005). None of these variables changed in the insulin-sensitive group. These results indicate that: (1) CHD risk factors in obese women vary as a function of being insulin-resistant or insulin-sensitive; (2) dramatic variations in insulin-mediated glucose disposal do not modulate weight loss in response to calorie-restricted diets, and (3) weight loss is effective in reducing CHD risk in insulin-resistant, obese women. Given these data, it seems obvious that attempts to reduce CHD risk factors by weight loss should focus on obese individuals who are also insulin-resistant.

Appetite Depressants↗
PubMed2000

Alterations in nitric oxide/cyclic-GMP pathway in nondiabetic siblings of patients with type 2 diabetes.

In this study, we have compared resistance to insulin-mediated glucose disposal and plasma concentrations of nitric oxide (NO) and cyclic-GMP in healthy volunteers with (n = 35) or without (n = 27) at least one sibling and one parent with type 2 diabetes. The 62 volunteers were further divided into groups of those with normal glucose tolerance or impaired glucose tolerance. Insulin-mediated glucose disposal was quantified by determining the insulin sensitivity index (ISI) in response to a low-dose, constant infusion of insulin (25 mU/kg x h) and glucose (4 mg/kg x min) for 150 min. The mean (+/-SEM) ISI [(mL kg(-1) min(-1)/pmol/L) x 10(3)] was significantly greater in those without a family history (30.3 +/- 2.3) as compared with nondiabetic volunteers with a family history of type 2 diabetes, whether they had normal glucose tolerance (17.0 +/- 7.2) or impaired glucose tolerance (9.5 +/- 1.4). In addition, basal NO levels, evaluated by the measurement of its stable end products [i.e. nitrite and nitrate levels (NO2-/ NO3-)], were significantly higher, and cyclic-GMP levels, its effector messenger, were significantly lower in those with a family history, irrespective of their degree of glucose tolerance, when compared with healthy volunteers without a family history of type 2 diabetes. Furthermore, when the 62 volunteers were analyzed as one group, there was a negative correlation between ISI and NO2-/NO3- levels (r = -0.35; P < 0.005) and a positive correlation between ISI and cyclic-GMP levels (r = 0.30; P < 0.02). These results have shown that alterations of the NO/cyclic-GMP pathway seem to be an early event in nondiabetic individuals with a family history of type 2 diabetes and these changes are correlated with the degree of insulin resistance.

Blood Glucose↗
PubMed2000

Carbohydrate-induced hypertriglyceridemia: an insight into the link between plasma insulin and triglyceride concentrations.

This study was initiated to test the hypothesis that endogenous hypertriglyceridemia results from a defect in the ability of insulin to inhibit the release of very low-density lipoprotein-triglyceride (TG) from the liver. To accomplish this goal, plasma glucose, insulin, free fatty acid (FFA), and TG concentrations were compared in 12 healthy volunteers, in response to diets containing either 40% or 60% of total calories as carbohydrate (CHO). The protein content of the two diets was similar (15% of calories), and the fat content varied inversely with the amount of CHO (45% or 25%). The diets were consumed in random order, and measurements were made of plasma glucose, insulin, FFA, and TG concentrations at the end of each dietary period, fasting, and at hourly intervals following breakfast and lunch. The results indicated that the 60% CHO diet resulted in higher fasting plasma TG concentrations associated with higher day-long plasma insulin and TG concentrations, and lower FFA concentrations. These results do not support the view that hypertriglyceridemia is secondary to a failure of insulin to inhibit hepatic TG secretion.

Blood Glucose↗
PubMed2000

Insulin resistance and hypertension. Patients in double jeopardy for cardiovascular disease.

Essential hypertension is prevalent among older individuals, and approximately 50% of persons with hypertension can be considered to have insulin resistance and hyperinsulinemia. It appears likely that insulin resistance and hyperinsulinemia predispose to, rather than result from, hypertension. Insulin resistance is associated with abnormalities in lipoprotein metabolism, hypercoagulability, and endothelial function, which probably account in part for the increased cardiovascular risk among hypertensive patients. To identify this subset of patients, all hypertensive patients should be screened for diabetes and lipid abnormalities. The presence of impaired glucose tolerance, diabetes, or hypertriglyceridemia and low HDL suggest the presence of insulin resistance. Insulin resistant patients, in particular, will benefit from exercise and weight loss.

Aged↗
PubMed1999

Differences in insulin resistance do not predict weight loss in response to hypocaloric diets in healthy obese women.

The current study was initiated to determine whether insulin resistance and/or hyperinsulinemia affected the ability of obese individuals to lose weight in response to hypocaloric diets. Thirty-one obese, nondiabetic women, with values for body mass index ranging from 28.0-35.0 kg/m2, volunteered for this program. Resistance to insulin-mediated glucose disposal was assessed by determining their steady state plasma insulin and glucose concentration during the last 30 min of a 180-min infusion of somatostatin, insulin, and glucose. The total integrated insulin response to breakfast and lunch was also determined. After the baseline measurements, volunteers were placed on a hypocaloric diet calculated to lead to a minimum weekly loss of 1% of ideal body weight. Individuals who met the criteria after 30 days of dieting were defined as weight loss successes (n = 20) and continued on the diet for another 30 days. Individuals not meeting the criteria were designated as weight loss failures (n = 12) and were discharged from the study. There was a mean (+/-SEM) weight loss at 60 days of 9.2 +/- 0.4 kg in the 20 individuals defined as weight loss successes, but there was no correlation between weight loss and either steady state plasma glucose or the total integrated insulin response (r < 0.1; P > 0.83). Furthermore, using the same criteria to define insulin sensitivity and insulin resistance as those for therapeutic successes, the therapeutic failures comprised six insulin-sensitive and five insulin-resistant subjects. In summary, insulin-mediated glucose disposal varied widely in nondiabetic, obese women, and there was no relationship between baseline insulin resistance or total integrated insulin response and weight loss. It is concluded that the ability to lose weight on a calorie-restricted diet over a short time period does not vary in obese, healthy women as a function of insulin resistance or hyperinsulinemia.

Adult↗
PubMed1998

Diabetes and dyslipidemia. A new model for transplant coronary artery disease.

BACKGROUND: Clinical observations suggest that transplant coronary artery disease (TxCAD) is immunologically mediated but may be accelerated by metabolic derangements. We developed a rat model of heterotopic heart transplantation in the presence of diabetes and dyslipidemia to further study their role in TxCAD development. METHODS AND RESULTS: Major histocompatibility complex-mismatched strains of inbred rats underwent heterotopic heart transplantation (ACI-to-Lewis allografts). Diabetes (DM) was induced by streptozotocin injection (80 mg/kg) after transplantation; dyslipidemia was worsened by feeding of a 60% high-fructose diet (+F). Allograft transplants were divided into four groups: (1) +DM/+F; (2) +DM/-F; (3) -DM/+F; and (4) -DM/-F. Isograft transplants (Lewis to Lewis, +DM/+/-F) were controls. All animals received daily cyclosporine (5 mg/kg). Grafts surviving > 30 days were evaluated for TxCAD on histological sections and graded 0 to 5 for intimal thickness. All streptozotocin-treated animals were diabetic within 2 weeks, with fourfold increases in plasma glucose concentrations versus nondiabetics. Severe TxCAD was observed in diabetic allografts only. The mean grade of TxCAD in diabetic allografts was 3.2 +/- 0.5 versus 1.1 +/- 0.4 in diabetic isografts (P < 0.03) and zero TxCAD in nondiabetic allografts (P < or = 0.0001). Fructose feeding resulted in a 1.5-fold higher triglyceride and a 1.3-fold higher cholesterol level versus the regular diet (-F) but showed no independent contribution to the development of TxCAD. CONCLUSIONS: These findings suggest that metabolic derangements associated with diabetes play an important role in TxCAD development in heterotopic ACI-to-Lewis rat heart transplantation. In this model of TxCAD in major histocompatibility complex-mismatched, diabetic, and dyslipidemic rats, immunologic and metabolic mechanisms that contribute to TxCAD can be further delineated and approaches to its prevention assessed.

Animals↗
PubMed1997

Effect of variations in plasma magnesium concentration on resistance to insulin-mediated glucose disposal in nondiabetic subjects.

Eighteen nondiabetic volunteers were selected for these studies on the basis of their plasma magnesium (Mg) concentrations defined as being either high (> 0.83 mmol/L) or low (< 0.80 mmol/L). Although different in Mg concentration (0.90 +/- 0.02 vs. 0.73 +/- 0.01 mmol/L), the 2 groups were comparable in terms of age, gender distribution, body mass index, and waist to hip girth. Measurements were made of their plasma glucose and insulin concentrations in response to a 75-g oral glucose load and the steady state plasma insulin and glucose (SSPG) concentrations at the end of an 180-min infusion of octreotide, insulin, and glucose. The low Mg group had significantly higher plasma glucose (P < 0.001) and insulin (P < 0.002) concentrations after the oral glucose challenge. Although the steady state plasma insulin concentrations were similar during the infusion study, the SSPG concentration was significantly (P < 0.001) greater in the low Mg group (11.9 +/- 0.9 vs. 6.6 +/- 0.9 mmol/L). Finally, when the 18 patients were analyzed together, there were significant (P < 0.05 to P < 0.01) inverse correlations between Mg concentrations and glucose (r = -0.68) and insulin (r = -0.51) areas and SSPG concentrations (r = -0.60). Thus, a low Mg concentration in nondiabetic subjects was associated with relative insulin resistance, glucose intolerance, and hyperinsulinemia.

Adult↗
PubMed1996

Coronary artery intimal thickening in the transplanted heart. An in vivo intracoronary untrasound study of immunologic and metabolic risk factors.

This study examined the hypothesis that immunologic factors are the major correlates of coronary artery intimal thickening and luminal stenosis. The study population included 116 adult heart transplant recipients with a mean age of 44.7 +/- 12.0 years (89 men and 27 women) undergoing annual coronary angiography and intracoronary ultrasound 3.4 +/- 2.7 (range, 1.0-14.6) years after transplantation. Mean intimal thickness was obtained from several distinct sites along the left anterior descending and/or left circumflex coronary artery by intracoronary ultrasound. Coronary artery stenosis defined by angiography was classified as mild (< 30% luminal stenosis), moderate (> or = 30-70% luminal stenosis), or severe (> 70% luminal stenosis or diffuse pruning of distal vessels). Prevalence of any transplant coronary artery disease (TxCAD) was 85% by intracoronary ultrasound and 15% by angiography. By multiple regression analysis, only average fasting plasma triglyceride level (P < 0.006) and average weight (P < 0.007) were significantly correlated with severity of intimal thickening (R = 0.54, P < 0.0001). Donor age (P < 0.006) and average fasting plasma triglyceride level (P < 0.009) were significantly correlated with stenosis by angiography. Correlation of multiple immunologic and metabolic factors with intimal thickness by univariate analysis suggests a multifactorial etiology for TxCAD. Among the multiple univariate correlates of TxCAD, higher fasting plasma triglyceride levels and body weight are the only independent correlates of TxCAD. The absence of acute rejection as an independent predictor of intimal thickening suggests that mechanisms beyond those mediating typical cellular rejection should be targeted for advancing our understanding of Tx-CAD.

Adult↗
PubMed1996

Similar weight loss with low- or high-carbohydrate diets.

The goal of this study was to evaluate the effect of diets that were equally low in energy but widely different in relative amounts of fat and carbohydrate on body weight during a 6-wk period of hospitalization. Consequently, 43 adult, obese persons were randomly assigned to receive diets containing 4.2 MJ/d (1000 kcal/d) composed of either 32% protein, 15% carbohydrate, and 53% fat, or 29% protein, 45% carbohydrate, and 26% fat. There was no significant difference in the amount of weight loss in response to diets containing either 15% (8.9 +/- 0.6 kg) or 45% (7.5 +/- 0.5 kg) carbohydrate. Furthermore, significant decreases in total body fat and waist-to-hip circumference were seen in both groups, and the magnitude of the changes did not vary as a function of diet composition. Fasting plasma glucose, insulin, cholesterol, and triacylglycerol concentrations decreased significantly in patients eating low-energy diets that contained 15% carbohydrate, but neither plasma insulin nor triacylglycerol concentrations fell significantly in response to the higher-carbohydrate diet. The results of this study showed that it was energy intake, not nutrient composition, that determined weight loss in response to low-energy diets over a short time period.

Adipose Tissue↗
PubMed1993

Mechanism of hypertriglyceridemia in Dahl rats.

Plasma triglyceride concentrations were shown to be higher in hypertensive (153 +/- 2 mm Hg) male Dahl salt-sensitive rats than in control Sprague-Dawley rats (122 +/- 2 mm Hg). These differences in triglyceride concentrations were seen when blood was drawn at 9 AM from unfasted animals (229 +/- 27 versus 111 +/- 8 mg/dL), at 1 PM after a 4-hour fast (186 +/- 13 versus 88 +/- 4 mg/dL), or at 9 AM after a 13-hour fast (151 +/- 6 versus 90 +/- 6 mg/dL), all p < 0.001. Total triglyceride secretion was also compared in groups of rats by determining the increment in plasma triglyceride concentration for 2 hours after blocking triglyceride removal from plasma by injecting Triton. Studies performed at 1 PM and 9 AM, after the 4- and 13-hour fast, demonstrated that total triglyceride secretion was greater (p < 0.05) in Dahl rats only when studied at 1 PM. Direct estimates of hepatic triglyceride secretion at 1 PM also demonstrated a significant (p < 0.02) increase in secretion rate by perfused livers from Dahl rats, due in part to their increased liver size. In addition, removal of prelabeled very low density lipoprotein-triglyceride in the intact rat was significantly (p < 0.05) decreased in Dahl rats. Lipoprotein lipase activity measured in skeletal muscle, heart, and adipose tissue was also significantly decreased at 9 AM and 1 PM (after 0 and 4 hours of fasting) in tissue from Dahl rats. These data confirm that Dahl rats have higher plasma triglyceride concentrations than Sprague-Dawley rats. Since both total and hepatic triglyceride secretion were somewhat greater in Dahl rats, in association with a decrease in both removal of very low density lipoprotein from plasma and decreased muscle and adipose tissue lipoprotein lipase activity, it seems likely that hypertriglyceridemia in Dahl rats results from a combination of increased triglyceride secretion and decreased triglyceride removal.

Adipose Tissue↗
PubMed1991

Effect of anatomical site on insulin action and insulin receptor phosphorylation in isolated rat adipocytes.

The effects of insulin were evaluated on adipocytes isolated from three different anatomical sites in male, Sprague-Dawley rats: epididymal (EPI), retroperitoneal (RP), and dorsal subcutaneous (SC). The results indicated that maximal insulin-stimulated glucose transport was significantly lower (P less than 0.001) in cells from the SC region as compared to EPI and RP cells. In addition, the ED50 value for SC cells (259 +/- 34 pmol/l) was significantly higher than for EPI (66 +/- 5 pM) or RP adipocytes (111 +/- 32 pmol/l). Insulin inhibition of catecholamine-induced lipolysis was also significantly greater (P less than 0.001) in EPI cells as compared to RP or SC adipocytes, and that was true when expressed in absolute or relative terms. The decrease in the ability of insulin to either stimulate glucose transport or inhibit catecholamine induced lipolysis in SC cells was associated with a decrease in insulin receptor autophosphorylation and receptor tyrosine kinase activity. These data show that insulin action on isolated adipocytes varies as a function of anatomical site, and that these changes are associated with variations in insulin receptor autophosphorylation and insulin receptor tyrosine kinase activity.

Adipose Tissue↗
PubMed1991

Insulin-resistance and associated risk factors for coronary heart disease as seen in families.

Recent reports have shown that resistance to insulin-stimulated glucose uptake, increased plasma glucose and insulin response to oral glucose, and hypertriglyceridemia can be seen in first degree relatives of patients with type 2 diabetes. We have recently shown that very similar metabolic changes can be seen in hyperinsulinemic individuals who have either normal or impaired glucose tolerance (IGT). Given these data, we thought it would be of interest to compare the plasma glucose and insulin response to an oral glucose challenge, plasma lipid concentrations, and blood pressure in offspring of parents with IGT as compared to offspring of parents with normal glucose tolerance. Parents with IGT had higher plasma insulin and triglyceride levels and blood pressure than those with normal glucose tolerance. The two groups of offspring were young, non-obese and similar in terms of age, gender distribution and body mass index. Statistically significant increases in plasma insulin response to oral glucose and in systolic and diastolic blood pressure were present in the offspring of parents with IGT. Demonstration of similar abnormalities in plasma insulin response to glucose and blood pressure regulation in patients with IGT and in their offspring is consistent with the view that individual differences in insulin metabolism and blood pressure are modulated by genetic factors and that both may be related to variations in insulin-stimulated glucose uptake and/or plasma insulin concentration.

Blood Glucose↗
PubMed1988

Abnormal lipid metabolism in treated hypertensive patients with non-insulin-dependent diabetes mellitus.

Plasma lipid, lipoprotein, and apoprotein concentrations were measured in 169 patients with non-insulin-dependent diabetes mellitus (NIDDM), 78 with normal blood pressure, and 91 diagnosed and receiving drug treatment for hypertension. Plasma triglyceride, cholesterol, low-density lipoprotein-cholesterol, and apoprotein B concentrations were significantly higher (p = less than 0.05 to less than 0.001) in the hypertensive group. In addition, the ratios of high-density to low-density lipoprotein-cholesterol and of apoprotein A-1 to apoprotein B were significantly reduced (p less than 0.01) in patients with hypertension. The changes noted were independent of differences in sex distribution, degree of obesity, and level of glycemic control. These results indicate that substantial differences in plasma lipid, lipoprotein, and apoprotein concentrations are seen when normotensive patients with NIDDM are compared with patients who are also being treated for hypertension, and that all of the changes noted would increase the risk of coronary artery disease in the hypertensive group. Since all patients with hypertension were receiving anti-hypertensive medications, it is not clear if it is hypertension per se, or its treatment, that is responsible for the observed changes in lipid metabolism.

Antihypertensive Agents↗
PubMed1988

Effect of a low fat diet on carbohydrate metabolism in patients with hypertension.

Plasma glucose and insulin responses to both a 75-g oral glucose challenge and to conventional meals were determined in eight patients with hypertension and compared with values of a control population. The results indicated that patients with hypertension had significantly higher than normal plasma glucose and insulin concentrations in both situations. Furthermore, when dietary carbohydrate was increased by 16% of total calories (with a reciprocal reduction in dietary fat), the hyperglycemia and hyperinsulinemia present in patients with hypertension were accentuated. Since low fat-high carbohydrate diets are usually recommended for patients with hypertension, these data suggest that abnormalities of glucose and insulin metabolism associated with hypertension would be increased if patients with high blood pressure followed conventional dietary advice. Since hyperglycemia and hyperinsulinemia have been shown to be associated with an increased risk of developing coronary artery disease, it may be appropriate to reevaluate the clinical utility of low fat-high carbohydrate diets in the treatment of hypertension.

Blood Glucose↗