Bio

Clinical Focus


  • Endocrinology / Diabetes
  • Endocrinology
  • Diabetes andMetabolism

Academic Appointments


Administrative Appointments


  • Diabetes Task Force, Chair, Stanford Hospital (2004 - Present)
  • GCRC Advisory Committee, member, Stanford University (2003 - Present)

Honors & Awards


  • Junior Physician Investigator Award, American Federation for Medical Research (2004)

Professional Education


  • Residency:Santa Clara Valley Medical Center (1997) CA
  • Internship:Santa Clara Valley Medical Center (1995) CA
  • Fellowship:Stanford University School of Medicine (2000) CA
  • Internship:UCSF Medical Center (1994) CA
  • M.S., Stanford University, Epidemiology (2004)
  • M.D., U.C. San Francisco, Medicine (1994)
  • M.S., U.C. Berkeley, Public Health (1992)
  • B.A., Stanford University, Human Biology (1988)

Research & Scholarship

Current Research and Scholarly Interests


Dr. McLaughlin conducts a number of clinical research studies related to obesity, insulin resistance, diabetes, and cardiovascular disease. Current studies include: 1) the impact of macronutrient composition on weight loss and cardiocascular risk (diabetic and nondiabetic patients); 2) comparison of weight loss and cardiovascular risk reduction in diabetic patients treated with different classes of antihyperglycemic drugs; 3) the role of the adipocyte in modulating insulin resistance

Clinical Trials


  • Obesity, Weight Loss, and Cardiovascular Disease Risk Recruiting

    The goal of the study is to define the roles played by resistance to insulin-mediated glucose disposal (insulin resistance) and circulating plasma insulin concentrations in: 1) ability to lose weight; 2) reduction of risk for coronary heart disease as a result of weight loss. We hypothesize that in the setting of caloric restriction, manipulating endogenous insulin concentrations will not alter ability of subjects to lose weight, but will lead to different reduction in CHD risk factors. To test this hypothesis, two parallel studs will be performed. First, obese insulin-resistant individuals will be randomized to one of two equally-hypocaloric diets that vary moderately in proportion of carbohydrate and mono/polyunsaturated fats (lower carbohydrate diet will be associated with greater reduction in endogenous insulin secretion). Second, diabetics treated with insulin secretagogues will be compared to diabetics treated with insulin sensitizers with respect to the same outcomes (secretagogues increase insulin secretion and insulin sensitizers decrease insulin concentrations). Endpoints include weight loss, change in insulin resistance, blood pressure, lipid and lipoproteins, markers of endothelial function, daylong insulin and glucose concentrations: these will be compared, in each of the parallel studies, between the group with insulin-stimulating intervention vs the group with the insulin-sparing intervention.

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Teaching

2013-14 Courses


Postdoctoral Advisees


Graduate and Fellowship Programs


Publications

Journal Articles


  • Plasma Glucose and Insulin Regulation Is Abnormal Following Gastric Bypass Surgery with or Without Neuroglycopenia OBESITY SURGERY Kim, S. H., Liu, T. C., Abbasi, F., Lamendola, C., Morton, J. M., Reaven, G. M., McLaughlin, T. L. 2009; 19 (11): 1550-1556

    Abstract

    Enhanced insulin sensitivity is commonly seen following Roux-en-Y gastric bypass surgery (RYGB) whereas symptomatic hypoglycemia post-RYGB seems to occur infrequently. It is unclear how different plasma glucose and insulin responses are in patients with symptomatic hypoglycemia (SX-RYGB) versus those who remain asymptomatic (ASX-RYGB), nor when compared with non-surgical controls with varying degrees of insulin sensitivity.Plasma glucose and insulin concentrations were determined following a 75-g oral glucose challenge in five groups: symptomatic and asymptomatic patients following RYGB (n = 9 each) and overweight/obese controls, divided into three subgroups (n = 30 each) on the basis of degree of insulin sensitivity measured by the insulin suppression test.SX-RYGB group had higher 30-min glucose after oral glucose compared with the ASX-RYGB group (p = 0.04). The two groups did not differ in peak glucose and insulin concentrations, nadir glucose concentration, or insulin-to-glucose ratio 30 min after oral glucose. These values were significantly different from the three control groups, and peak insulin concentrations post-RYGB were increased at every degree of insulin sensitivity as compared with the control groups.Plasma glucose and insulin responses to oral glucose in patients with symptomatic hypoglycemia post-RYGB are minimally different when compared to individuals who remain asymptomatic, and both groups demonstrate hyperinsulinemia out of proportion to their degree of insulin sensitivity.

    View details for DOI 10.1007/s11695-009-9893-8

    View details for Web of Science ID 000271282900014

    View details for PubMedID 19557485

  • Persistence of improvement in insulin sensitivity following a dietary weight loss programme DIABETES OBESITY & METABOLISM McLaughlin, T., Schweitzer, P., Carter, S., Yen, C., Lamendola, C., Abbasi, F., Reaven, G. 2008; 10 (12): 1186-1194

    Abstract

    Short-term dietary weight loss can improve insulin resistance but long-term studies are lacking. We sought to quantify the degree to which maintenance of weight loss after a short-term dietary intervention was associated with persistent metabolic benefits.Fifty-seven insulin-resistant obese subjects had insulin-mediated glucose disposal quantified through the steady-state plasma glucose (SSPG) test, and associated metabolic risk markers quantified at baseline, after a 16-week dietary weight loss intervention, and in 25 subjects, at follow-up of 28.8 +/- 13 months. Changes in metabolic variables over time were analysed and correlation with weight loss ascertained. Those with greatest vs. least long-term SSPG response (responders vs. non-responders) were compared. Multivariate analysis was performed for predictors of persistent SSPG response.At follow-up, the 25 subjects who returned for metabolic testing had, on average, maintained their weight loss. Insulin-mediated glucose disposal remained significantly improved vs. baseline, as did plasma triglyceride and HDL cholesterol (HDL-C) concentrations, and improvement correlated with total amount of weight lost. Comparison of SSPG responders to non-responders showed no difference in amount of weight lost and SSPG change during the 16-week dietary intervention; however, SSPG non-responders regained 2.6% of weight lost, whereas responders lost an additional 1.5% at follow-up (p < 0.05 vs. non-responders). Non-responders had baseline characteristics consistent with more severe insulin resistance, including higher fasting plasma glucose (p = 0.03). Long-term SSPG change was independently predicted by both total weight loss (p = 0.005) and baseline fasting plasma glucose (p = 0.007).Improvement in insulin sensitivity is maintained for 2-3 years following dietary weight loss if weight is not regained. Triglyceride and HDL-C concentrations also remain improved over time, consistent with improvement in insulin sensitivity. Fasting glucose and weight regain predict less long-term response in insulin sensitivity. These results highlight the potential long-term benefits of weight loss and importance of preventing weight regain among high-risk individuals.

    View details for DOI 10.1111/j.1463-1326.2008.00877.x

    View details for Web of Science ID 000260528300005

    View details for PubMedID 18476986

  • Insulin resistance is associated with a modest increase in inflammation in subcutaneous adipose tissue of moderately obese women DIABETOLOGIA McLaughlin, T., Deng, A., Gonzales, O., AILLAUD, M., Yee, G., Lamendola, C., Abbasi, F., Connolly, A. J., Sherman, A., Cushman, S. W., Reaven, G., Tsao, P. S. 2008; 51 (12): 2303-2308

    Abstract

    We have previously described differences in adipose cell size distribution and expression of genes related to adipocyte differentiation in subcutaneous abdominal fat obtained from insulin-sensitive (IS) and -resistant (IR) persons, matched for degree of moderate obesity. To determine whether other biological properties also differ between IR and IS obese individuals, we quantified markers of inflammatory activity in adipose tissue from overweight IR and IS individuals.Subcutaneous abdominal tissue was obtained from moderately obese women, divided into IR (n = 14) and IS (n = 19) subgroups by determining their steady-state plasma glucose (SSPG) concentrations during the insulin suppression test. Inflammatory activity was assessed by comparing expression of nine relevant genes and by immunohistochemical quantification of CD45- and CD68-containing cells.SSPG concentrations were approximately threefold higher in IR than in IS individuals. Expression levels of CD68, EMR1, IL8, IL6 and MCP/CCL2 mRNAs were modestly but significantly increased (p < 0.05) in IR compared with IS participants. Results of immunohistochemical staining were consistent with gene expression data, demonstrating modest differences between IR and IS individuals. Crown-like structures, in which macrophages surround single adipocytes, were rarely seen in tissue from either subgroup.A modest increase in inflammatory activity was seen in subcutaneous adipose tissue from IR compared with equally obese IS individuals. Together with previous evidence of impaired adipose cell differentiation in IR vs equally obese individuals, it appears that at least two biological processes in subcutaneous adipose tissue characterize the insulin-resistant state independent of obesity per se.

    View details for DOI 10.1007/s00125-008-1148-z

    View details for Web of Science ID 000260686000019

    View details for PubMedID 18825363

  • Pioglitazone administration decreases cardiovascular disease risk factors in insulin-resistant smokers METABOLISM-CLINICAL AND EXPERIMENTAL Abbasi, F., Farin, H. M., Lemendola, C., McGraw, L., McLaughlin, T., Reaven, G. M. 2008; 57 (8): 1108-1114

    Abstract

    Insulin sensitivity varies in cigarette smokers, and there is evidence that cardiovascular disease (CVD) risk is greatest in those smokers who are also insulin resistant. To extend these observations, we sought to (1) compare CVD risk factors in smokers who do not plan to stop smoking, divided into insulin-resistant (IR) and insulin-sensitive (IS) subgroups, and (2) evaluate the ability of drug-induced changes in insulin sensitivity to decrease CVD risk. Thirty-six cigarette smokers were divided into IR (n = 19) and IS (n = 17) subgroups by determining their steady-state plasma glucose (SSPG) concentrations during the insulin suppression test (the higher the SSPG, the more insulin resistant the individual). In addition, baseline measurements were made of fasting lipid and lipoprotein concentrations; inflammatory markers; and daylong glucose, insulin, and free fatty acid responses to test meals. All subjects were treated with pioglitazone for 12 weeks, after which all baseline measurements were repeated. Baseline triglyceride and high-density lipoprotein cholesterol concentrations were significantly different in IR as compared with IS smokers (P < .05) both before and after adjustment for differences in sex and body mass index. After pioglitazone treatment, SSPG concentration significantly fell in the IR smokers (P < .001), associated with a significant improvement in the atherogenic lipoprotein profile seen at baseline (P < or = .03) and a decrease in soluble intercellular adhesion molecule 1 and C-reactive protein concentrations (P = .01 and .02, respectively), whereas the IS smokers only had a significant increase in high-density lipoprotein cholesterol (P = .004) and a decrease in soluble intercellular adhesion molecule 1 (P = .02) and CRP (P = .07) levels. In conclusion, cigarette smokers have profound differences in CVD risk factors related to their degree of insulin sensitivity. It is suggested that, in addition to smoking cessation efforts, attention should be given to identifying the subgroup of smokers most at risk for CVD, but unwilling or unable to stop smoking, and to initiating appropriate therapeutic interventions to decrease CVD in this high-risk group.

    View details for DOI 10.1016/j.metabol.2008.03.016

    View details for Web of Science ID 000258196300014

    View details for PubMedID 18640389

  • Clinical experience with a relatively low carbohydrate, calorie-restricted diet improves insulin sensitivity and associated metabolic abnormalities in overweight, insulin resistant South Asian Indian women ASIA PACIFIC JOURNAL OF CLINICAL NUTRITION Backes, A. C., Abbasi, F., Lamendola, C., McLaughlin, T. L., Reaven, G., Palaniappan, L. P. 2008; 17 (4): 669-671

    Abstract

    South Asian Indians are at increased risk for cardiovascular disease associated with insulin resistance and a dyslipidemia characterized by high triglyceride and low high-density lipoprotein cholesterol concentrations. The purpose of this study is to determine the effects of a calorie-restricted, relatively low carbohydrate diet on weight loss, insulin sensitivity, and associated cardiovascular disease risk factors in overweight, insulin resistant, but apparently healthy, South Asian Indian women. Twenty-three, overweight, insulin resistant, apparently healthy, South Asian Indian women were advised on a calorie-restricted diet containing 40 percent carbohydrate for 3 months. Change in weight, insulin sensitivity (quantified by the steady state plasma glucose concentration during the insulin suppression test), and associated cardiovascular disease risk factors were measured. Weight fell from 75.5 to 70.5 kg (p<0.001), associated with significant decreases in diastolic blood pressure, plasma concentrations (mg/dL) of steady state plasma glucose (217 to 176, p<0.001), triglycerides (137 to 101, p = 0.003), and glucose (98 to 92, p = 0.005). A calorie-restricted diet, moderately lower in carbohydrate, can lead to weight loss, decreased insulin resistance, and reduction in several cardiovascular disease risk factors in overweight, insulin resistant, apparently healthy, South Asian Indian women.

    View details for Web of Science ID 000262520400020

    View details for PubMedID 19114407

  • Enhanced proportion of small adipose cells in insulin-resistant vs insulin-sensitive obese individuals implicates impaired adipogenesis DIABETOLOGIA McLaugblin, T., Sherman, A., Tsao, P., Gonzalez, O., Yee, G., Lamendola, C., Reaven, G. M., Cusbman, S. W. 2007; 50 (8): 1707-1715

    Abstract

    The biological mechanism by which obesity predisposes to insulin resistance is unclear. One hypothesis is that larger adipose cells disturb metabolism via increased lipolysis. While studies have demonstrated that cell size increases in proportion to BMI, it has not been clearly shown that adipose cell size, independent of BMI, is associated with insulin resistance. The aim of this study was to test this widely held assumption by comparing adipose cell size distribution in 28 equally obese, otherwise healthy individuals who represented extreme ends of the spectrum of insulin sensitivity, as defined by the modified insulin suppression test.Subcutaneous periumbilical adipose tissue biopsy samples were fixed in osmium tetroxide and passed through the Beckman Coulter Multisizer to obtain cell size distributions. Insulin sensitivity was quantified by the modified insulin suppression test. Quantitative real-time PCR for adipose cell differentiation genes was performed for 11 subjects.All individuals exhibited a bimodal cell size distribution. Contrary to expectations, the mean diameter of the larger cells was not significantly different between the insulin-sensitive and insulin-resistant individuals. Moreover, insulin resistance was associated with a higher ratio of small to large cells (1.66 +/- 1.03 vs 0.94 +/- 0.50, p = 0.01). Similar cell size distributions were observed for isolated adipose cells. The real-time PCR results showed two- to threefold lower expression of genes encoding markers of adipose cell differentiation (peroxisome proliferator-activated receptor gamma1 [PPARgamma1], PPARgamma2, GLUT4, adiponectin, sterol receptor element binding protein 1c) in insulin-resistant compared with insulin-sensitive individuals.These results suggest that after controlling for obesity, insulin resistance is associated with an expanded population of small adipose cells and decreased expression of differentiation markers, suggesting that impairment in adipose cell differentiation may contribute to obesity-associated insulin resistance.

    View details for DOI 10.1007/s00125-007-0708-y

    View details for Web of Science ID 000248225100017

    View details for PubMedID 17549449

  • Clinical efficacy of two hypocaloric diets that vary in overweight patients with type 2 diabetes - Comparison of moderate fat versus carbohydrate reductions DIABETES CARE McLaughlin, T., Carter, S., Lamendola, C., Abbasi, F., Schaaf, P., Basina, M., Reaven, G. 2007; 30 (7): 1877-1879

    View details for DOI 10.2337/dc07-0301

    View details for Web of Science ID 000247768400036

    View details for PubMedID 17475941

  • Lipoprotein abnormalities are associated with insulin resistance in South Asian Indian women METABOLISM-CLINICAL AND EXPERIMENTAL Palaniappan, L. P., Kwan, A. C., Abbasi, F., Lamendola, C., McLaughlin, T. L., Reaven, G. M. 2007; 56 (7): 899-904

    Abstract

    South Asian Indians are at increased risk of coronary heart disease (CHD), possibly related to dyslipidemia characterized by high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations. The importance of differences in insulin resistance as compared to abdominal obesity in the development of this atherogenic lipoprotein profile is not clear, and the current cross-sectional study was initiated to examine this issue. Consequently, we defined the relationship between differences in insulin-mediated glucose uptake (IMGU), abdominal obesity, and various measures of lipoprotein metabolism known to increase CHD risk in 52 apparently healthy women of South Asian Indian ancestry. IMGU was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test and abdominal obesity was assessed by measurement of waist circumference (WC), and the population was divided into tertiles on the basis of their SSPG results. Results indicated that although there were significant differences in SSPG, TG, and HDL-C values, there were no differences in age, blood pressure, total cholesterol, low-density lipoprotein cholesterol, body mass index, or WC between the highest and lowest tertiles. SSPG concentrations were significantly correlated with both log TG (r = 0.44, P = .001) and HDL-C (r = -0.44, P < .001) concentration, whereas TG and HDL-C concentrations were not significantly related to WC. Furthermore, the relationships between SSPG concentration and TG and HDL-C remained significant when adjusted for age and WC. Finally, a more extensive lipoprotein analysis indicated that the most insulin resistant tertile had higher TG concentrations, lower concentrations of HDL-C and HDL-C subclasses, and smaller and denser low-density lipoprotein particles than the most insulin sensitive tertile, despite the 2 groups not being different in age, BMI, or WC. These results indicate that a highly atherogenic lipoprotein profile seen in South Asian Indian women is significantly associated with insulin resistance independent of differences in WC.

    View details for DOI 10.1016/j.metabol.2007.01.020

    View details for Web of Science ID 000247542300007

    View details for PubMedID 17570249

  • Serum alanine aminotransferase levels decrease further with carbohydrate than fat restriction in insulin-resistant adults DIABETES CARE Ryan, M. C., Carter, S., Abbasi, F., McLaughlin, T. L., Lamendola, C. 2007; 30 (5): 1075-1080

    Abstract

    Although weight loss interventions have been shown to reduce steatosis in nonalcoholic fatty liver disease (NAFLD), the impact of dietary macronutrient composition is unknown. We assessed the effect on serum alanine aminotransferase (ALT) concentrations of two hypocaloric diets varying in amounts of carbohydrate and fat in obese insulin-resistant individuals, a population at high risk for NAFLD.Post hoc analysis of ALT concentrations was performed in 52 obese subjects with normal baseline values and insulin resistance, as quantified by the steady-state plasma glucose (SSPG) test, who were randomized to hypocaloric diets containing either 60% carbohydrate/25% fat or 40% carbohydrate/45% fat (15% protein) for 16 weeks. The primary end point was change in ALT, which was evaluated according to diet, weight loss, SSPG, and daylong insulin concentrations.Although both diets resulted in significant decreases in weight and SSPG, daylong insulin, and serum ALT concentrations, the 40% carbohydrate diet resulted in greater decreases in SSPG (P < 0.04), circulating insulin (P < 0.01), and ALT (9.5 +/- 9.4 vs. 4.2 +/- 8.3 units/l; P < 0.04) concentrations. ALT changes correlated with improvement in insulin sensitivity (P = 0.04) and daylong insulin (P < 0.01). Individuals with ALT concentrations above the proposed upper limits experienced significant declines in ALT, unlike those with lower ALT levels.In a population at high risk for NAFLD, a hypocaloric diet moderately lower in carbohydrate decreased serum ALT concentrations to a greater degree than a higher-carbohydrate/low-fat diet, despite equal weight loss. This may result from a relatively greater decline in daylong insulin concentrations. Further research with histological end points is needed to further explore this finding.

    View details for DOI 10.2337/dc06-2169

    View details for Web of Science ID 000246291400007

    View details for PubMedID 17351275

  • Heterogeneity in the prevalence of risk factors for cardiovascular disease and type 2 diabetes mellitus in obese individuals - Effect of differences in insulin sensitivity ARCHIVES OF INTERNAL MEDICINE McLaughlin, T., Abbasi, F., Lamendola, C., Reaven, G. 2007; 167 (7): 642-648

    Abstract

    The possibility that substantial heterogeneity in metabolic abnormalities exists in moderately obese individuals has not been emphasized in studies of the effect of obesity on morbidity and mortality. We tested the hypothesis that risk factors for type 2 diabetes mellitus and cardiovascular disease vary dramatically in moderately obese individuals as a function of differences in a specific measure of insulin sensitivity.Participants included 211 apparently healthy, obese (body mass index [calculated as weight in kilograms divided by height in meters squared], 30.0-34.9) volunteers for weight loss studies. Main outcome measures included insulin-mediated glucose uptake as quantified by the insulin suppression test and metabolic variables known to increase the risk for type 2 diabetes and cardiovascular disease.Insulin sensitivity varied 6-fold. When compared with the most insulin-sensitive third, the most insulin-resistant third of the population had significantly higher (P<.001) systolic and diastolic blood pressure (139 +/- 20 vs 123 +/- 18 mm Hg, and 83 +/- 3 vs 75 +/- 10 mm Hg, respectively), higher fasting and 2-hour oral glucose load concentrations (103 +/- 11 vs 95 +/- 11 mg/dL [5.7 +/- 0.6 vs 5.3 +/- 0.6 mmol/L], and 139 +/- 30 vs 104 +/- 19 mg/dL [7.7 +/- 1.7 vs 5.8 +/- 1.1 mmol/L], respectively), higher plasma triglyceride concentrations (198 +/- 105 vs 114 +/- 51 mg/dL [2.2 +/- 1.2 vs 1.3 +/- 0.6 mmol/L]), lower plasma high-density lipoprotein cholesterol concentrations (41 +/- 9 vs 50 +/- 13 mg/dL [1.1 +/- 0.2 vs 1.3 +/- 0.3 mmol/L]), and more prevalent impaired glucose tolerance (47% vs 2%).The magnitude of risk factors for type 2 diabetes and cardiovascular disease varies markedly in moderately obese individuals as a function of differences in degree of insulin sensitivity. Because not all moderately obese individuals are at similar risk for developing type 2 diabetes and cardiovascular disease, intensive therapeutic interventions should be addressed to the insulin-resistant subset of this population.

    View details for Web of Science ID 000245628700003

    View details for PubMedID 17420421

  • The relationship between insulin resistance and dyslipidaemia in cigarette smokers DIABETES OBESITY & METABOLISM Farin, H. M., Abbasi, F., Kim, S. H., Lamendola, C., McLaughlin, T., Reaven, G. M. 2007; 9 (1): 65-69

    Abstract

    Considerable evidence shows that cigarette smokers tend to have the dyslipidemic pattern of high plasma triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations, a highly atherogenic lipoprotein profile also typical of the insulin-resistant state even in the absence of cigarette smoking. However, because cigarette smokers are frequently insulin resistant, it is unclear if this dyslipidaemia is secondary to smoking, per se, or simply to the fact that smokers tend to be insulin resistant. The present study was initiated to determine whether this dyslipidaemia prevalent in cigarette smokers and characteristic of insulin-resistant individuals is a function of cigarette smoking or of insulin resistance.As measured using vertical auto profile-II methodology, the lipid and lipoprotein concentrations were compared in 34 cigarette smokers divided into insulin-sensitive and insulin-resistant subgroups. The two groups were similar in age and body mass index, differing only in their insulin-mediated glucose uptake as quantified by the steady-state plasma glucose concentration determined during the insulin suppression test.While levels of TG and very low-density lipoprotein cholesterol (VLDL-C) were significantly elevated in insulin-resistant cigarette smokers, total cholesterol (C), low-density lipoprotein cholesterol (LDL-C), narrow-density (ND) LDL-C, intermediate-density lipoprotein-C (IDL-C), HDL-C and non-HDL-C were not different in the two groups. The insulin-resistant smokers also had a preponderance of small, dense LDL particles, while the reverse was true of the insulin-sensitive cigarette smokers.These data suggest that the dyslipidaemia previously attributed to smoking occurs primarily in those smokers who are also insulin resistant.

    View details for DOI 10.1111/j.1463-1326.2006.00574.x

    View details for Web of Science ID 000242781700008

    View details for PubMedID 17199720

  • The relationship between plasma adiponectin concentration and insulin resistance is altered in smokers JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Abbasi, F., Farin, H. M., Lamendola, C., McLaughlin, T., Schwartz, E. A., Reaven, G. M., Reaven, P. D. 2006; 91 (12): 5002-5007

    Abstract

    Low plasma adiponectin concentrations in smokers may contribute to the adverse consequences that occur in these individuals.The objective of the study was to define the relationship among smoking, plasma adiponectin concentrations, insulin resistance, and inflammation.This was a cross-sectional, observational study with a 2 x 2 factorial design and a prospective longitudinal arm.The study was conducted at a general clinical research center.Apparently healthy smokers (n = 30) and nonsmokers (n = 30), subdivided into insulin resistant (IR) (n = 15) and insulin sensitive (IS) (n = 15) subgroups participated in the study.Intervention included pioglitazone administration for 3 months to 12 IR smokers and eight IS smokers. MAIN OUTCOME MEASUres: Measures included fasting plasma adiponectin and C-reactive protein (CRP) concentrations and changes in adiponectin after pioglitazone treatment in IR and IS smokers.Being either a smoker or having insulin resistance was independently associated with lower adiponectin concentrations (P = 0.046 and 0.001, respectively). The difference in mean adiponectin concentration between smokers and nonsmokers did not depend on the insulin resistance status of the subjects. No difference was detected in average CRP concentrations between smokers and nonsmokers (P = 0.18) and between IR and IS subjects (P = 0.13). CRP concentrations were unrelated to adiponectin in smokers (r = -0.05, P = 0.78) and nonsmokers (r = 0.03, P = 0.86). Finally, pioglitazone treatment increased adiponectin concentrations in both IR (P < 0.001) and IS smokers (P = 0.001).Plasma adiponectin concentrations are lower in smokers and IR subjects and are unrelated to CRP concentrations. These findings suggest that low levels of adiponectin in smokers may be independent of both insulin resistance and a generalized inflammatory response.

    View details for DOI 10.1210/jc.2006-0419

    View details for Web of Science ID 000242581300045

    View details for PubMedID 17003098

  • Effects of moderate variations in macronutrient composition on weight loss and reduction in cardiovascular disease risk in obese, insulin-resistant adults AMERICAN JOURNAL OF CLINICAL NUTRITION McLaughlin, T., Carter, S., Lamendola, C., Abbasi, F., Yee, G., Schaaf, P., Basina, M., Reaven, G. 2006; 84 (4): 813-821

    Abstract

    Obese, insulin-resistant persons are at risk of cardiovascular disease. How best to achieve both weight loss and clinical benefit in these persons is controversial, and recent reports questioned the superiority of low-fat diets.We aimed to ascertain the effects of moderate variations in the carbohydrate and fat content of calorie-restricted diets on weight loss and cardiovascular disease risk in obese, insulin-resistant persons.Fifty-seven randomly assigned, insulin-resistant, obese persons completed a 16-wk calorie-restricted diet with 15% of energy as protein and either 60% and 25% or 40% and 45% of energy as carbohydrate and fat, respectively. Baseline and postweight-loss insulin resistance; daylong glucose, insulin, and triacylglycerol concentrations; fasting lipid and lipoprotein concentrations; and markers of endothelial function were quantified.Weight loss with 60% or 40% of energy as carbohydrate (5.7 +/- 0.7 or 6.9 +/- 0.7 kg, respectively) did not differ significantly, and improvement in insulin sensitivity correlated with the amount of weight lost (r = 0.50, P < 0.001). Subjects following the diet with 40% of energy as carbohydrate had greater reductions in daylong insulin and triacylglycerol (P < 0.05) and fasting triacylglycerol (0.53 mmol/L; P = 0.04) concentrations, greater increases in HDL-cholesterol concentrations (0.12 mmol/L; P < 0.01) and LDL particle size (1.82 s; P < 0.05), and a greater decrease in plasma E-selectin (5.6 ng/L; P = 0.02) than did subjects following the diet with 60% of energy as carbohydrate.In obese, insulin-resistant persons, a calorie-restricted diet, moderately lower in carbohydrate and higher in unsaturated fat, is as efficacious as the traditional low-fat diet in producing weight loss and may be more beneficial in reducing markers for cardiovascular disease risk.

    View details for Web of Science ID 000241140700019

    View details for PubMedID 17023708

  • Plasma asymmetric dimethylarginine concentrations are elevated in obese insulin-resistant women and fall with weight loss JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM McLaughlin, T., Stuhlinger, M., Lamendola, C., Abbasi, F., Bialek, J., Reaven, G. M., Tsao, P. S. 2006; 91 (5): 1896-1900

    Abstract

    Plasma asymmetric dimethylarginine (ADMA) concentrations are higher in apparently healthy, insulin-resistant (IR) individuals and decrease in response to thiazolidenedione treatment.The objective of the study was to determine whether ADMA concentrations would also fall when insulin sensitivity is enhanced with weight loss in obese individuals. DESIGN/SETTING/PATIENTS/INTERVENTION: Twenty obese women classified as IR or insulin sensitive (IS) on the basis of their steady-state plasma glucose (SSPG) concentration during the insulin suppression test underwent 12 wk of dietary weight loss.Plasma glucose, insulin, and ADMA were measured at baseline and after weight loss; change in insulin resistance was quantified by repeating the SSPG after the dietary intervention.Although weight loss was similar in the two groups, significant improvements in SSPG, glucose, and insulin concentrations were confined to the IR group. Baseline plasma ADMA concentrations (mean +/- sd) were higher in IR subjects (1.69 +/- 0.44 vs. 1.18 +/- 0.45 micromol/liter, P = 0.02) and decreased to 1.20 +/- 0.22 micromol/liter (P < 0.001) with weight loss. In contrast, ADMA levels did not change with a similar extent of weight loss in the IS group.Plasma ADMA levels are higher in obese, IR women than in equally obese, IS women and decrease in response to weight loss when associated with enhancement of insulin sensitivity.

    View details for DOI 10.1210/jc.2005-1441

    View details for Web of Science ID 000237330000043

    View details for PubMedID 16507636

  • Metabolic and ovarian effects of rosiglitazone treatment for 12 weeks in insulin-resistant women with polycystic ovary syndrome HUMAN REPRODUCTION Cataldo, N. A., Abbasi, F., McLaughlin, T. L., Basina, M., Fechner, P. Y., Giudice, L. C., Reaven, G. M. 2006; 21 (1): 109-120

    Abstract

    Insulin sensitizers have favourable metabolic and ovarian effects in polycystic ovary syndrome (PCOS). This study examined rosiglitazone, a thiazolidinedione, in PCOS.In a prospective, open-label study, the effects of rosiglitazone on metabolism and ovarian function were examined in 42 non-diabetic women with PCOS classified according to the National Institute of Child Health and Human Development criteria and insulin resistance (IR) by steady-state plasma glucose (SSPG) > or =10 mmol/l on octreotide-modified insulin suppression testing. Participants were randomized to rosiglitazone 2, 4 or 8 mg daily for 12 weeks. Endpoints included ovulation and menstrual pattern; serum testosterone, sex hormone-binding globulin (SHBG), and LH; and changes in IR and glucose-insulin responses on 8 h mixed-meal profile.After rosiglitazone 8 mg daily for 12 weeks, SSPG declined and insulinaemia fell by 46%; lower doses gave lesser effects. Serum LH, total and free testosterone were unchanged; SHBG increased. With rosiglitazone, ovulation occurred in 23/42 women (55%), without significant dose dependence. Both before and during treatment, ovulators on rosiglitazone had lower circulating insulin and free testosterone and higher SHBG than non-ovulators. Testosterone declined only in a subgroup of ovulators with early vaginal bleeding after starting rosiglitazone.Rosiglitazone in insulin-resistant PCOS promoted ovulation and dose-dependently decreased IR and insulinaemia; ovulators had lower circulating insulin and testosterone.

    View details for DOI 10.1093/humrep/dei289

    View details for Web of Science ID 000233846700014

    View details for PubMedID 16155076

  • Is there a simple way to identify insulin-resistant individuals at increased risk of cardiovascular disease? AMERICAN JOURNAL OF CARDIOLOGY McLaughlin, T., Reaven, G., Abbasi, F., Lamendola, C., Saad, M., Waters, D., Simon, J., Krauss, R. M. 2005; 96 (3): 399-404

    Abstract

    The goal of this study was to evaluate the ability of various routine measures of lipoprotein metabolism to identify patients who were insulin resistant and dyslipidemic, and therefore, at increased risk of cardiovascular disease. For this purpose, insulin resistance was quantified by determining the steady-state plasma glucose concentration during the insulin suppression test in 449 apparently healthy patients. The low-density lipoprotein (LDL) particle diameter and subclass phenotype were measured by gradient gel electrophoresis in 1,135 patients. Pearson's correlation coefficients and receiver-operating characteristic curves were used to evaluate measures of lipoprotein metabolism as potential markers of insulin resistance and LDL phenotype. The results indicated that the ratio of the plasma concentrations of triglyceride to high-density lipoprotein cholesterol was the best predictor of insulin resistance and LDL particle diameter. The optimal triglyceride/high-density lipoprotein cholesterol ratio for predicting insulin resistance and LDL phenotype was 3.5 mg/dl; a value that identified insulin-resistant patients with a sensitivity and specificity comparable to the criteria currently proposed to diagnose the metabolic syndrome. The sensitivity and specificity were even greater for identification of patients with small, dense, LDL particles. In conclusion, a plasma triglyceride/high-density lipoprotein cholesterol concentration ratio > or =3.5 provides a simple means of identifying insulin-resistant, dyslipidemic patients who are likely to be at increased risk of cardiovascular disease.

    View details for DOI 10.1016/j.amjcard.2005.03.085

    View details for Web of Science ID 000231057000017

    View details for PubMedID 16054467

  • Rosiglitazone reduces glucose-stimulated insulin secretion rate and increases insulin clearance in nondiabetic, insulin-resistant individuals DIABETES Kim, S. H., Abbasi, F., Chu, J. W., McLaughlin, T. L., Lamendola, C., Polonsky, K. S., Reaven, G. M. 2005; 54 (8): 2447-2452

    Abstract

    Compensatory hyperinsulinemia permitting insulin-resistant individuals to maintain normal glucose tolerance is associated with a left shift in the glucose-stimulated insulin secretion rate (GS-ISR) dose-response curve and decrease in the insulin metabolic clearance rate (I-MCR). To see whether these changes would reverse with improvement in insulin sensitivity, 14 nondiabetic insulin-resistant subjects received rosiglitazone for 12 weeks (4 mg daily for 4 weeks and then 8 mg daily for 8 weeks). Insulin-mediated glucose uptake was quantified by measuring the steady-state plasma glucose concentration during the insulin suppression test. GS-ISR and I-MCR were determined during a 240-min graded intravenous glucose infusion. I-MCR was also calculated during the insulin suppression test. After rosiglitazone treatment, insulin sensitivity improved with significant fall in steady-state plasma glucose (means +/- SE from 13.5 +/- 0.62 to 9.8 +/- 1.02 mmol/l, P < 0.001). In response, the integrated GS-ISR decreased by 21% (P < 0.001), with a right shift in the dose-response curve. Calculated I-MCR increased by 34% (P = 0.008) during the insulin suppression test and by 21% (P = 0.03) during the graded glucose infusion. In conclusion, enhanced insulin sensitivity in rosiglitazone-treated nondiabetic insulin-resistant individuals was associated with a shift to the right in the GS-ISR dose-response curve and an increase in I-MCR.

    View details for Web of Science ID 000230869500023

    View details for PubMedID 16046313

  • Effect of rosiglitazone treatment on circulating vascular and inflammatory markers in insulin-resistant subjects. Diabetes & vascular disease research Chu, J. W., Abbasi, F., Lamendola, C., McLaughlin, T., Reaven, G. M., Tsao, P. S. 2005; 2 (1): 37-41

    Abstract

    Thiazolidinedione (TZD) compounds enhance insulin sensitivity and attenuate inflammation. The effect of the TZD compound, rosiglitazone (RSG) on both actions was evaluated in two groups of insulin-resistant subjects with minimal elevations of fasting plasma glucose (PG) concentration: group A (n=15, PG < 7.0 mmol/L) and group B (n=14, PG 7.0-8.3 mmol/L). Insulin action, quantified by the insulin suppression test, improved after three months of treatment in both groups, and concentrations of C-reactive protein, plasminogen activator inhibitor-1 and Eselectin all fell. Significant decreases in L-selectin and P-selectin were confined to group B, and concentrations of interleukin-6, intercellular adhesion molecule-1 and vascular cellular adhesion molecule-1 did not fall in either group. Significant relationships were not discerned between enhanced insulin sensitivity and related variables and decreases in inflammatory/vascular markers, suggesting that RSG-induced changes in the latter variables in insulin-resistant individuals might be at least partly independent of the effects of the drug on insulin action.

    View details for PubMedID 16305071

  • Comparative effects of rosuvastatin and gomfibrozil on glucose, insulin, and lipid metabolism in insulin m resistant, nondiabetic patients with combined dyslipidemia AMERICAN JOURNAL OF CARDIOLOGY Lamendola, C., Abbasi, F., Chu, J. W., Hutchinson, H., Cain, V., Leary, E., McLaughlin, T., Stein, E., Reaven, G. 2005; 95 (2): 189-193

    Abstract

    To evaluate the pharmacologic intervention most likely to decrease cardiovascular disease risk in insulin-resistant patients with combined dyslipidemia, 39 patients with this abnormality were assessed before and after 3 months of treatment with gemfibrozil (1,200 mg/day) or rosuvastatin (40 mg/day) with regard to: (1) steady-state plasma glucose concentration at the end of a 180-minute infusion of octreotide, insulin, and glucose; (2) fasting lipid, lipoprotein, and apolipoprotein concentrations; and (3) daylong glucose, insulin, triglyceride, and remnant lipoprotein cholesterol concentrations in response to breakfast and lunch. The 2 groups were similar at baseline in age, gender, body mass index and in measurements of carbohydrate and lipoprotein metabolism. Neither gemfibrozil nor rosuvastatin enhanced insulin sensitivity or lowered daylong glucose and insulin concentrations in insulin-resistant patients with combined dyslipidemia, but both drugs significantly decreased fasting triglyceride concentrations. However, only rosuvastatin treatment significantly (p <0.05 to <0.001) reduced fasting low-density lipoprotein cholesterol, apolipoprotein B-100, apolipoprotein C-III, apolipoprotein C-III:B particles, the apolipoprotein B-100:apolipoprotein A-I ratio, and increased apolipoprotein A-I (p <0.05). The degree of improvement in fasting and postprandial remnant lipoprotein cholesterol concentrations was significantly greater (p <0.05) in rosuvastatin-treated patients, and this difference in the relative effectiveness of the drugs was also true of the decrease in non-high-density lipoprotein cholesterol concentrations.

    View details for DOI 10.1016/j.amjcard.2004.09.005

    View details for Web of Science ID 000226461000006

    View details for PubMedID 15642550

  • Prevalence of insulin resistance and associated cardiovascular disease risk factors among normal weight, overweight, and obese individuals METABOLISM-CLINICAL AND EXPERIMENTAL McLaughlin, T., Allison, G., Abbasi, F., Lamendola, C., Reaven, G. 2004; 53 (4): 495-499

    Abstract

    Obese individuals tend to be both insulin resistant and at increased risk to develop cardiovascular disease (CVD). Given the increased prevalence of obesity in the US population, we thought it important to define the relationship between degree of obesity and insulin-mediated glucose disposal in the population at large, as well as the relationship between obesity, insulin resistance, and CVD risk in these individuals. To do this we quantified insulin-mediated glucose disposal in 465 healthy volunteers by determining the steady-state plasma glucose (SSPG) concentrations at the end of a 180-minute infusion of somatostatin, insulin, and glucose. Adiposity was estimated by body mass index (BMI) and the relationship between BMI and SSPG defined. In addition, a series of CVD risk factors were measured, including blood pressure, plasma glucose, and insulin concentrations, before and after 75 g of oral glucose, and fasting plasma lipid and lipoprotein concentrations. The results indicated that SSPG concentration and BMI were significantly correlated (r = 0.54, P >.001), and 36% of individuals in the most insulin-resistant tertile were obese (BMI >/= 30.0 kg/m(2)). However, 16% of those in the most insulin-resistant tertile were of normal weight (BMI < 25.0 kg/m(2)). Although CVD risk factors were accentuated in general with progressive increases in either BMI or SSPG concentration, important differences were noted. Thus, the higher the SSPG concentration, the more the increase in plasma glucose, insulin, and triglyceride (TG) concentrations, whereas the greater the BMI, the higher the low-density lipoprotein concentration. Furthermore, while CVD risk factors increased significantly with each tertile of insulin resistance, significant differences in CVD risk were only apparent when the lowest BMI tertile was compared with the other 2, with the values in the middle and upper BMI differing from each other. These results show that while BMI and insulin resistance are related, they are not synonymous, and that they make independent and different contributions to increasing CVD risk.

    View details for Web of Science ID 000220581500016

    View details for PubMedID 15045698

  • Discrimination between obesity and insulin resistance in the relationship with adiponectin DIABETES Abbasi, F., Chu, J. W., Lamendola, C., McLaughlin, T., Hayden, J., Reaven, G. M., Reaven, P. D. 2004; 53 (3): 585-590

    Abstract

    Insulin resistance and obesity are both associated with lower plasma adiponectin concentrations. Since insulin resistance and obesity are related, the extent to which the association of adiponectin with insulin resistance is dependent on its relationship with obesity is unclear. To address this issue, fasting plasma adiponectin concentrations were measured in 60 nondiabetic subjects, stratified into four equal groups on the basis of both their degree of adiposity and insulin resistance. Insulin resistance was quantified by determining the steady-state plasma glucose (SSPG) concentration in response to an infusion of octreotide, glucose, and insulin, and degree of adiposity was assessed by BMI. Subjects were defined as obese (BMI >/=30.0 kg/m(2)) or nonobese (<27.0 kg/m(2)) and as either insulin sensitive (SSPG <100 mg/dl) or insulin resistant (>190 mg/dl). Insulin-resistant subjects had significantly (P<0.001) lower (mean +/- SD) adiponectin concentrations, whether they were obese (17.1 +/- 5.9 micro g/ml) or nonobese (16.3 +/- 7.5 micro g/ml) as compared with either obese, insulin-sensitive (34.3 +/- 13.1 micro g/ml) or nonobese, insulin-sensitive (29.8 +/- 15.3 micro g/ml) subjects. Finally, adiponectin levels in insulin-sensitive subjects varied to a significantly greater degree than in insulin-resistant subjects. These results suggest that adiponectin concentrations are more closely related to differences in insulin-mediated glucose disposal than obesity.

    View details for Web of Science ID 000189307500010

    View details for PubMedID 14988241

  • Plasma adiponectin concentrations do not increase in association with moderate weight loss in insulin-resistant, obese women METABOLISM-CLINICAL AND EXPERIMENTAL Abbasi, F., Lamendola, C., McLaughlin, T., Hayden, J., Reaven, G. M., Reaven, P. D. 2004; 53 (3): 280-283

    Abstract

    Plasma adiponectin concentrations were measured before and after moderate weight loss in 20 obese women, divided at baseline into insulin-resistant (IR) and insulin-sensitive (IS) subgroups on the basis of their steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of octreotide, glucose, and insulin. The groups were similar in age and body weight and lost comparable amounts of weight (8 to 9 kg) during the weight loss period. Fasting plasma insulin and SSPG concentrations were significantly higher (P <.001) and adiponectin concentrations somewhat lower (P =.10) in the IR group (P <.001) at baseline. Both SSPG and plasma insulin concentrations decreased in IR subjects (P <.001), but did not change in IS individuals. Adiponectin concentrations did not change with weight loss in either group. Thus, neither weight loss, per se, nor enhanced insulin sensitivity resulted in a change in plasma adiponectin concentrations.

    View details for DOI 10.1016/j.metabol.2003.10.004

    View details for Web of Science ID 000220333600004

    View details for PubMedID 15015137

  • Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus METABOLISM-CLINICAL AND EXPERIMENTAL Abbasi, F., Chu, J. W., McLaughlin, T., Lamendola, C., Leary, E. T., Reaven, G. M. 2004; 53 (2): 159-164

    Abstract

    In light of the conflicting results of the recent United Kingdom Prospective Study (UKPDS), where diabetic patients on metformin monotherapy had lower all-cause mortality and the addition of metformin in sulfonylurea-treated patients was associated with an increased risk of diabetes-related death, we sought to compare the effects on cardiovascular disease (CVD) risk factors of metformin monotherapy with metformin treatment when added to a sulfonylurea compound in patients with type 2 diabetes. Thirty-one volunteers with type 2 diabetes mellitus, 16 on dietary therapy and 15 on sulfonylurea monotherapy (SU), were treated with metformin for 12 weeks. Measurements were made of (1) fasting plasma glucose, hemoglobin A(1c) (HbA(1c)), lipid, remnant lipoprotein cholesterol (RLP-C) levels, and low-density lipoprotein (LDL) particle size; (2) daylong plasma glucose, insulin, free fatty acid (FFA), triglyceride (TG), and RLP-C concentrations; and (3) fasting levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin). Fasting plasma glucose concentrations decreased to a similar degree after treatment with metformin in both the metformin monotherapy group (12.45 +/- 0.48 v 9.46 +/- 0.47 mmol/L, P <.001) and the combined SU and metformin therapy group (14.09 +/- 0.51 v 10.57 +/- 0.85 mmol/L, P =.001). Fasting plasma lipid concentrations and LDL particle size did not significantly change in either treatment group, whereas fasting RLP-C concentrations were significantly lower in the metformin monotherapy group (0.43 +/- 0.09 v 0.34 +/- 0.07 mmol/L, P =.02). Daylong concentrations of plasma glucose, FFA, TG, and RLP-C were lower to a similar degree in both treatment groups, whereas daylong plasma insulin concentrations were unchanged. Fasting plasma sVCAM-1 levels were significantly lower in both the metformin monotherapy group (484 +/- 19 v 446 +/- 18 ng/mL, P =.02) and the combined SU and metformin therapy group (496 +/- 29 v 456 +/- 31 ng/mL, P =.05), whereas fasting plasma sICAM-1 and sE-selectin levels were essentially unchanged. Administration of metformin, either as monotherapy or in combination with a sulfonylurea drug, improved glycemic control and led to a decrease in several CVD risk factors in patients with type 2 diabetes.

    View details for DOI 10.1016/j.metabol.2003.07.020

    View details for Web of Science ID 000188797400007

    View details for PubMedID 14767866

  • Obesity, insulin resistance, and cardiovascular disease RECENT PROGRESS IN HORMONE RESEARCH, VOL 59 Reaven, G., Abbasi, F., McLaughlin, T. 2004; 59: 207-223

    Abstract

    The ability of insulin to stimulate glucose disposal varies more than six-fold in apparently healthy individuals. The one third of the population that is most insulin resistant is at greatly increased risk to develop cardiovascular disease (CVD), type 2 diabetes, hypertension, stroke, nonalcoholic fatty liver disease, polycystic ovary disease, and certain forms of cancer. Between 25-35% of the variability in insulin action is related to being overweight. The importance of the adverse effects of excess adiposity is apparent in light of the evidence that more than half of the adult population in the United States is classified as being overweight/obese, as defined by a body mass index greater than 25.0 kg/m(2). The current epidemic of overweight/obesity is most-likely related to a combination of increased caloric intake and decreased energy expenditure. In either instance, the fact that CVD risk is increased as individuals gain weight emphasizes the gravity of the health care dilemma posed by the explosive increase in the prevalence of overweight/obesity in the population at large. Given the enormity of the problem, it is necessary to differentiate between the CVD risk related to obesity per se, as distinct from the fact that the prevalence of insulin resistance and compensatory hyperinsulinemia are increased in overweight/obese individuals. Although the majority of individuals in the general population that can be considered insulin resistant are also overweight/obese, not all overweight/obese persons are insulin resistant. Furthermore, the cluster of abnormalities associated with insulin resistance - namely, glucose intolerance, hyperinsulinemia, dyslipidemia, and elevated plasma C-reactive protein concentrations -- is limited to the subset of overweight/obese individuals that are also insulin resistant. Of greater clinical relevance is the fact that significant improvement in these metabolic abnormalities following weight loss is seen only in the subset of overweight/obese individuals that are also insulin resistant. In view of the large number of overweight/obese subjects at potential risk to be insulin resistant/hyperinsulinemic (and at increased CVD risk), and the difficulty in achieving weight loss, it seems essential to identify those overweight/obese individuals who are also insulin resistant and will benefit the most from weight loss, then target this population for the most-intensive efforts to bring about weight loss.

    View details for Web of Science ID 000189490300010

    View details for PubMedID 14749503

  • Use of metabolic markers to identify overweight individuals who are insulin resistant ANNALS OF INTERNAL MEDICINE McLaughlin, T., Abbasi, F., Cheal, K., Chu, J., Lamendola, C., Reaven, G. 2003; 139 (10): 802-809

    Abstract

    Insulin resistance is more common in overweight individuals and is associated with increased risk for type 2 diabetes mellitus and cardiovascular disease. Given the current epidemic of obesity and the fact that lifestyle interventions, such as weight loss and exercise, decrease insulin resistance, a relatively simple means to identify overweight individuals who are insulin resistant would be clinically useful.To evaluate the ability of metabolic markers associated with insulin resistance and increased risk for cardiovascular disease to identify the subset of overweight individuals who are insulin resistant.Cross-sectional study.General clinical research center.258 nondiabetic, overweight volunteers.Body mass index; fasting glucose, insulin, lipid and lipoprotein concentrations; and insulin-mediated glucose disposal as quantified by the steady-state plasma glucose concentration during the insulin suppression test. Overweight was defined as body mass index of 25 kg/m2 or greater, and insulin resistance was defined as being in the top tertile of steady-state plasma glucose concentrations. Receiver-operating characteristic curve analysis was used to identify the best markers of insulin resistance; optimal cut-points were identified and analyzed for predictive power.Plasma triglyceride concentration, ratio of triglyceride to high-density lipoprotein cholesterol concentrations, and insulin concentration were the most useful metabolic markers in identifying insulin-resistant individuals. The optimal cut-points were 1.47 mmol/L (130 mg/dL) for triglyceride, 1.8 in SI units (3.0 in traditional units) for the triglyceride-high-density lipoprotein cholesterol ratio, and 109 pmol/L for insulin. Respective sensitivity and specificity for these cut-points were 67%, 64%, and 57% and 71%, 68%, and 85%. Their ability to identify insulin-resistant individuals was similar to the ability of the criteria proposed by the Adult Treatment Panel III to diagnose the metabolic syndrome (sensitivity, 52%, and specificity, 85%).Three relatively simple metabolic markers can help identify overweight individuals who are sufficiently insulin resistant to be at increased risk for various adverse outcomes. In the absence of a standardized insulin assay, we suggest that the most practical approach to identify overweight individuals who are insulin resistant is to use the cut-points for either triglyceride concentration or the triglyceride-high-density lipoprotein cholesterol concentration ratio.

    View details for Web of Science ID 000186663500002

    View details for PubMedID 14623617

  • Usefulness of plasma glucose and insulin concentrations in identifying patients with insulin resistance AMERICAN JOURNAL OF CARDIOLOGY Tuan, C. Y., Abbasi, F., Lamendola, C., McLaughlin, T., Reaven, G. 2003; 92 (5): 606-610

    Abstract

    In this study, a specific measurement of insulin-mediated glucose disposal was used in 490 healthy volunteers to classify subjects as being insulin resistant. We then made standard measurements of plasma glucose and insulin concentrations to see how useful they would be as surrogate markers of insulin resistance.

    View details for DOI 10.1016/S0002-9149(03)00735-5

    View details for Web of Science ID 000185060700024

    View details for PubMedID 12943888

  • Lipoprotein risk factors for cardiovascular disease in patients with type 2 diabetes mellitus treated with oral antihyperglycaemic agents DIABETES OBESITY & METABOLISM Chu, J. W., Abbasi, F., McLaughlin, T. L., Lamendola, C., Schaaf, P., Carlson, T. H., Leary, E. T., Reaven, G. M. 2003; 5 (5): 333-337

    Abstract

    To compare lipoprotein risk factors for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (DM) treated with a sulphonylurea (SU) compound only, metformin (MET) only, or combined SU + MET.The study population consisted of 62 patients with type 2 DM, whose antihyperglycaemic treatment program had been stable for at least 3 months, divided into three groups: 26 patients in the SU group, 17 patients in the MET group and 19 patients in the SU + MET group. None of the patients were taking lipid-lowering drugs. Fasting venous blood samples were taken to measure concentrations of glucose, total cholesterol, triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and remnant lipoprotein-cholesterol (RLP-C) as well as for determination of LDL particle diameter.The three groups were similar in terms of age, gender, body mass index and fasting plasma glucose concentrations. Total cholesterol concentrations were significantly lower (p < 0.05 for trend) in those treated with SU + MET as compared with the other two groups. However, there were no significant differences between the three groups in their plasma concentrations of TG, LDL-C, HDL-C or RLP-C; furthermore, the proportion of individuals within each treatment group with small LDL particle diameter was also not different.The lipoprotein profile of patients with type 2 DM, matched for level of fasting hyperglycaemia, was similar irrespective of treatment with SU alone, MET alone or SU + MET. Thus, we could not identify any changes in lipoprotein metabolism that could account for differences in risk of CVD as a function of treatment.

    View details for Web of Science ID 000185112800010

    View details for PubMedID 12940871

  • Multiple lipoprotein abnormalities associated with insulin resistance in healthy volunteers are identified by the vertical auto profile-II methodology CLINICAL CHEMISTRY Chu, J. W., Abbasi, F., Kulkarni, K. R., Lamendola, C., McLaughlin, T. L., Scalisi, J. N., Reaven, G. M. 2003; 49 (6): 1014-1017

    View details for Web of Science ID 000183088100041

    View details for PubMedID 12766017

  • Differentiation between obesity and insulin resistance in the association with C-reactive protein CIRCULATION McLaughlin, T., Abbasi, F., Lamendola, C., Liang, L., Reaven, G., Schaaf, P., Reaven, P. 2002; 106 (23): 2908-2912

    Abstract

    Plasma C-reactive protein (CRP) concentrations are increased in obese and/or hyperinsulinemic individuals. The goal of this study was to determine if the relation between insulin resistance and CRP was independent of obesity.Plasma CRP concentrations were measured before and after 3 months of calorie restriction in 38 healthy, obese women. Steady-state plasma glucose (SSPG) concentration during a 180-minute infusion of octreotide, glucose, and insulin was used to stratify participants into insulin-resistant (IR, n=20) or insulin-sensitive (n=18) groups, similar in terms of mean age (46+/-2 versus 44+/-2 years), body mass index (32.0+/-0.4 versus 31.4+/-0.3 kg/m2), and waist circumference (96+/-2 versus 95+/-2 cm). Mean CRP (0.39+/-0.08 versus 0.12+/-0.03 mg/dL, P=0.003) concentrations were higher in the IR group, as were day-long plasma glucose and insulin responses (P<0.001). There was a significant correlation at baseline between CRP and day-long plasma integrated insulin response (r=0.47, P=0.001) but not between CRP and body mass index (r=0.14) or waist circumference (r=0.10). Weight loss was similar in the two groups (8.7+/-0.9 versus 8.4+/-0.8 kg) but was associated with significant (P<0.001) decreases in SSPG and CRP concentrations in the IR group only. Regression analysis showed that SSPG and day-long plasma insulin response were the only significant predictors of CRP concentration.CRP concentrations are elevated predominantly in obese individuals who are also insulin resistant and fall in parallel with weight loss-associated improvements in insulin resistance. The relation between CRP concentrations and insulin resistance is independent of obesity.

    View details for DOI 10.1161/01.CIR.0000041046.32962.86

    View details for Web of Science ID 000179698600011

    View details for PubMedID 12460870

  • Comparison in patients with type 2 diabetes of fibric acid versus hepatic hydroxymethyl glutaryl- coenzyme a reductase inhibitor treatment of combined dyslipidemia METABOLISM-CLINICAL AND EXPERIMENTAL McLaughlin, T., Abbasi, F., Lamendola, C., Leary, E., Reaven, G. M. 2002; 51 (10): 1355-1359

    Abstract

    Patients with combined dyslipidemia are at greatly increased coronary heart disease (CHD) risk. The threat of rhabdomyolysis with dual pharmacologic treatment (hepatic hydroxymethyl glutaryl coenzyme A [HMG-CoA] reductase inhibitors plus fibric acid derivatives) has tended to limit therapy in patients with combined dyslipidemia to a choice of one or the other drug. Judgment of the potential benefits of either agent has rarely taken into account their effect on the postprandial accumulation of highly atherogenic, triglyceride (TG)-rich, remnant lipoprotein particles (RLPs). Because this information could be of substantial clinical relevance, we addressed this question in patients with type 2 diabetes and combined dyslipidemia by comparing the effects of gemfibrozil versus HMG-CoA reductase inhibitors (statins) on both fasting and postprandial lipid and lipoprotein concentrations. For this purpose, 22 patients with type 2 diabetes and combined dyslipidemia were randomized to treatment with either a statin or gemfibrozil for 3 months. Glycemic control was similar in both groups at baseline and did not change in response to treatment. Baseline lipid and lipoprotein concentrations were also similar in the 2 treatment groups, but the responses to therapy were quite different. Statin-treated patients had a statistically significant decrease in low-density lipoprotein (LDL) cholesterol concentration (156 mg/dL to 96 mg/dL, P <.001), whereas there was no change in patients treated with gemfibrozil. In contrast, there was a statistically significant decrease (P <.05) in plasma TG concentrations (116 mg/dL) in gemfibrozil-treated individuals, without any change in subjects treated with statins. However, the decrease in total integrated postprandial plasma RLP response measured hourly from 8 AM to 4 PM was not different in patients treated with either gemfibrozil (-43%) or statins (-34%). These results indicate that statin treatment, in addition to its beneficial effect on hypercholesterolemia, was as effective as gemfibrozil in reducing postprandial accumulation of triglyceride-rich, atherogenic RLPs in patients with type 2 diabetes and combined dyslipidemia. As such, the clinical utility of statin monotherapy in the treatment of combined dyslipidemia may have been underestimated.

    View details for DOI 10.1053/meta.2002.34713

    View details for Web of Science ID 000178587200021

    View details for PubMedID 12370858

  • Relationship between obesity, insulin resistance, and coronary heart disease risk JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Abbasi, F., Brown, B. W., Lamendola, C., McLaughlin, T., Reaven, G. M. 2002; 40 (5): 937-943

    Abstract

    The study goals were to: 1) define the relationship between body mass index (BMI) and insulin resistance in 314 nondiabetic, normotensive, healthy volunteers; and 2) determine the relationship between each of these two variables and coronary heart disease (CHD) risk factors.The importance of obesity as a risk factor for type 2 diabetes and hypertension is well-recognized, but its role as a CHD risk factor in nondiabetic, normotensive individuals is less well established.Insulin resistance was quantified by determining the steady-state plasma glucose (SSPG) concentration during the last 30 min of a 180-min infusion of octreotide, glucose, and insulin. In addition, nine CHD risk factors: age, systolic blood pressure, diastolic blood pressure (DBP), total cholesterol, triglycerides (TG), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein cholesterol concentrations, and glucose and insulin responses to a 75-g oral glucose load were measured in the volunteers.The BMI and the SSPG concentration were significantly related (r = 0.465, p < 0.001). The BMI and SSPG were both independently associated with each of the nine risk factors. In multiple regression analysis, SSPG concentration added modest to substantial power to BMI with regard to the prediction of DBP, HDL cholesterol and TG concentrations, and the glucose and insulin responses.Obesity and insulin resistance are both powerful predictors of CHD risk, and insulin resistance at any given degree of obesity accentuates the risk of CHD and type 2 diabetes.

    View details for Web of Science ID 000177765200014

    View details for PubMedID 12225719

  • Metformin treatment lowers asymmetric dimethylarginine concentrations in patients with type 2 diabetes METABOLISM-CLINICAL AND EXPERIMENTAL Asagami, T., Abbasi, F., Stuelinger, M., Lamendola, C., McLaughlin, T., Cooke, J. P., Reaven, G. M., Tsao, P. S. 2002; 51 (7): 843-846

    Abstract

    This study was initiated to see if plasma asymmetric dimethylarginine (ADMA) concentrations decreased in hyperglycemic patients with type 2 diabetes following metformin treatment, either as monotherapy or following its addition to sulfonylurea-treated patients. Fasting plasma glucose, dimethylarginine, and L-arginine concentrations were measured before and 3 months after the administration of a maximally effective dose of metformin to 31 patients with type 2 diabetes in poor glycemic control (fasting plasma concentrations > 9.7 mmol/L), while being treated with either diet (n = 16) or a maximal amount of a sulfonylurea compound (n = 15). Fasting plasma glucose concentration (mean +/- SEM) decreased to a similar degree (P <.01) in patients treated with either metformin alone (12.4 +/- 0.5 to 9.5 +/- 0.5 mmol/L) or when it was added to a sulfonylurea compound (14.1 +/- 0.5 to 10.6 +/- 0.9 mmol/L). The improvement in glycemic control was associated with similar decreases (P <.01) in ADMA concentrations in metformin (1.65 +/- 0.21 to 1.18 +/- 0.13 micromol/L) and sulfonylurea + metformin-treated patients (1.75 +/- 0.13 to 1.19 +/- 0.08 micromol/L). Plasma L-arginine concentrations were similar in the 2 groups at baseline and did not change in response to metformin. Thus, metformin treatment was associated with a favorable increase in the plasma L-arginine/ADMA ratio. These results provide the first evidence that plasma ADMA concentrations decrease in association with improved glycemic control in patients with type 2 diabetes and demonstrate that the magnitude of the change in metformin-treated patients was similar, irrespective of whether it was used as monotherapy or in combination with sulfonylurea treatment.

    View details for DOI 10.1053/meta.2002.33349

    View details for Web of Science ID 000176578200007

    View details for PubMedID 12077728

  • Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Stuhlinger, M. C., Abbasi, F., Chu, J. W., Lamendola, C., McLaughlin, T. L., Cooke, J. P., Reaven, G. M., Tsao, P. S. 2002; 287 (11): 1420-1426

    Abstract

    Increased levels of asymmetric dimethylarginine (ADMA) are associated with endothelial dysfunction and increased risk of cardiovascular disease. Several cardiovascular risk factors are associated with reduced sensitivity to insulin, but elevated ADMA concentrations have not been fully linked to the metabolic syndrome.To evaluate the relationship between insulin sensitivity and plasma ADMA concentrations, and to determine whether a pharmacological treatment that increases insulin sensitivity would also modulate ADMA concentrations.Cross-sectional study, containing a nonrandomized controlled trial component, of 64 healthy volunteers without diabetes (42 women, 22 men; 48 with normal blood pressure and 16 with hypertension), which was conducted at a university medical center between October 2000 and July 2001.Rosiglitazone (4 mg/d for 4 weeks and then 4 mg twice daily for 8 weeks), an insulin-sensitizing agent, was given to 7 insulin-resistant subjects with hypertension. These subjects were studied before and after 12-week treatment.Insulin sensitivity measured by the insulin suppression test, and fasting plasma levels of low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, glucose, insulin, and ADMA concentrations.Plasma ADMA concentrations were positively correlated with impairment of insulin-mediated glucose disposal in nondiabetic, normotensive subjects (r = 0.73; P<.001). Consistent with the metabolic syndrome, ADMA levels were also positively correlated with fasting triglyceride levels (r = 0.52; P<.001) but not with low-density lipoprotein cholesterol levels (r = 0.19; P =.20). Plasma ADMA concentrations increased in insulin-resistant subjects independent of hypertension. Pharmacological treatment improved insulin sensitivity and reduced mean (SD) plasma ADMA concentrations from 1.50 (0.30) to 1.05 (0.33) micromol/L (P =.001).A significant relationship exists between insulin resistance and plasma concentrations of ADMA. Pharmacological intervention with rosiglitazone enhanced insulin sensitivity and reduced ADMA levels. Increases in plasma ADMA concentrations may contribute to the endothelial dysfunction observed in insulin-resistant patients.

    View details for Web of Science ID 000174465000024

    View details for PubMedID 11903029

  • Plasma concentrations of asymmetric dimethylarginine are increased in patients with type 2 diabetes mellitus AMERICAN JOURNAL OF CARDIOLOGY Abbasi, F., Asagmi, T., Cooke, J. P., Lamendola, C., McLaughlin, T., Reaven, G. M., Stuehlinger, M., Tsao, P. S. 2001; 88 (10): 1201-?

    View details for Web of Science ID 000172412300025

    View details for PubMedID 11703973

  • Effect of insulin resistance on postprandial elevations of remnant lipoprotein concentrations in postmenopausal women AMERICAN JOURNAL OF CLINICAL NUTRITION Kim, H. S., Abbasi, F., Lamendola, C., McLaughlin, T., Reaven, G. M. 2001; 74 (5): 592-595

    Abstract

    Questions remain as to why postmenopausal women are at a higher risk of coronary artery disease (CAD) than are premenopausal women. Studies have shown that plasma concentrations of remnant lipoproteins (RLPs) are elevated in patients with CAD and that increases in plasma RLP concentrations may be related to variations in insulin-mediated glucose disposal.We sought to evaluate the possibility that postprandial accumulation of plasma RLPs will be accentuated in insulin-resistant, postmenopausal women.Postmenopausal women were divided into insulin-sensitive (n = 15) and insulin-resistant (n = 15) groups according to their steady state plasma glucose concentrations in response to a 180-min infusion of octreotide, insulin, and glucose. Plasma insulin, triacylglycerol, and RLP-cholesterol concentrations were measured either hourly (insulin) or every 2 h (triacylglycerol and RLP cholesterol) for 8 h, before and after breakfast (0800) and lunch (1200).By selection, insulin-resistant women had higher steady state plasma glucose concentrations than did insulin-sensitive women (10.8 +/- 0.5 compared with 4.1 +/- 5 mmol/L, respectively; P < 0.001), associated with higher fasting triacylglycerol (1.58 +/- 0.04 compared with 1.00 +/- 0.03 mmol/L; P = 0.01) and lower HDL-cholesterol (1.06 +/- 0.08 compared with 1.34 +/- 0.05; P = 0.01) concentrations. In addition, measurements of daylong concentrations of insulin, triacylglycerol, and RLP cholesterol were also significantly greater in insulin-resistant than in insulin-sensitive women (P < 0.001).Postprandial accumulation of RLPs is accentuated in insulin-resistant, postmenopausal women. This may contribute to the increased risk of CAD in these individuals.

    View details for Web of Science ID 000171779500009

    View details for PubMedID 11684526

  • Relationship between insulin resistance, weight loss, and coronary heart disease risk in healthy, obese women METABOLISM-CLINICAL AND EXPERIMENTAL McLaughlin, T., Abbasi, F., Kim, H. S., Lamendola, C., Schaaf, P., Reaven, G. 2001; 50 (7): 795-800

    Abstract

    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.

    View details for DOI 10.1053/meta.2001.24210

    View details for Web of Science ID 000169829600010

    View details for PubMedID 11436184

  • Metabolic changes following sibutramine-assisted weight loss in obese individuals: Role of plasma free fatty acids in the insulin resistance of obesity METABOLISM-CLINICAL AND EXPERIMENTAL McLaughlin, T., Abbasi, F., Lamendola, C., Kim, H. S., Reaven, G. M. 2001; 50 (7): 819-824

    Abstract

    The relationship between insulin-mediated glucose disposal and daylong free fatty acid (FFA) concentrations before and after sibutramine-assisted weight loss was investigated in 24 healthy, normotensive, nondiabetic, obese women (body mass index [BMI] >30.0 kg/m(2)). The 24 volunteers were defined as being insulin-resistant (IR) or insulin-sensitive (IS) on the basis of their steady-state plasma glucose (SSPG) concentration in response to a 180-minute continuous intravenous infusion of octreotide, insulin, and glucose. The mean (+/- SEM) SSPG concentrations were significantly higher (P <.001) in the IR group (219 +/- 7 v 69 +/- 6 mg/dL) at baseline. The IR group also had significantly higher plasma glucose (P =.002), insulin (P <.001), and FFA (P =.02) concentrations measured at hourly intervals from 8 AM to 4 PM, before and after breakfast (8 AM) and lunch (noon). Weight loss in response to an energy-restricted diet for 4 months and sibutramine (15 mg/d) was comparable in the 2 experimental groups (8.6 +/- 1.3 v 7.9 +/- 1.4 kg). SSPG concentrations decreased significantly (P <.001) following weight loss (219 +/- 7 to 144 +/- mg/dL) in the IR group, but there was no change in the SSPG of the IS group (69 +/- 6 to 73 +/- 7 mg/dL. The improvement in insulin sensitivity in the IR group after weight loss was associated with a significant decline in daylong plasma glucose (P >.001) and insulin (P =.02) concentrations, without a weight-loss-associated decrease in daylong plasma FFA responses. In contrast, there was no significant change in plasma glucose, insulin, and FFA concentrations following weight loss in the IS group. These results indicate that daylong FFA concentrations vary substantially in obese individuals as a function of whether they are IR or IS. Furthermore the observation that the IR group was more insulin-sensitive after weight loss, associated with lower daylong insulin concentrations in the absence of a significant decrease in circulating FFA concentrations, suggests that resistance to insulin-mediated glucose disposal in obese individuals cannot be entirely due to high FFA levels.

    View details for DOI 10.1053/meta.2001.24220

    View details for Web of Science ID 000169829600014

    View details for PubMedID 11436188

  • Carbohydrate-induced hypertriglyceridemia: An insight into the link between plasma insulin and triglyceride concentrations JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM McLaughlin, T., Abbasi, F., Lamendola, C., Yeni-Komshian, H., Reaven, G. 2000; 85 (9): 3085-3088

    Abstract

    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.

    View details for Web of Science ID 000089166200016

    View details for PubMedID 10999790

  • Insulin resistance and hypertension - Patients in double jeopardy for cardiovascular disease GERIATRICS McLaughlin, T., Reaven, G. 2000; 55 (6): 28-?

    Abstract

    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.

    View details for Web of Science ID 000087657800008

    View details for PubMedID 10872343

  • Plasma insulin concentration is more tightly linked to plasma leptin concentration than is the body mass index METABOLISM-CLINICAL AND EXPERIMENTAL Abbasi, F., Carantoni, M., McLaughlin, T., Reaven, G. M. 2000; 49 (4): 544-547

    Abstract

    This study tested the hypothesis that the integrated plasma insulin response to oral glucose is a more sensitive predictor of the fasting plasma leptin concentration than the body mass index (BMI) or waist to hip ratio (WHR). For this purpose, we determined the fasting plasma leptin concentration and plasma insulin response to a 75-g oral glucose challenge in 76 healthy female subjects, with a BMI of 19.1 to 36.6 kg/m2 and a WHR of 0.57 to 1.1. The results demonstrated that fasting plasma leptin concentrations were significantly correlated with both the BMI (r = .64, P < .001) and the plasma insulin response to glucose (r = .61, P < .001), but not with the WHR (r = .27). Since the BMI and the insulin response were also significantly related (r = .34, P = .003), multivariate analysis was performed to determine if the BMI and insulin response were independent determinants of the fasting leptin concentration. This analysis indicated that both the BMI and insulin response were significantly related to plasma leptin (P < .001). To pursue this issue further, the population was divided into tertiles on the basis of the (1) plasma leptin concentration, (2) BMI, and (3) integrated insulin response. The two variables that were most closely linked to each other were the leptin concentration and insulin response. In contrast, the BMI was relatively easily disassociated from the other two variables. These results indicate that while both the plasma insulin response to glucose and the BMI are significantly associated with the fasting plasma leptin concentration, the plasma insulin response appears more closely associated with the plasma leptin concentration.

    View details for Web of Science ID 000086444800023

    View details for PubMedID 10778883

  • The relationship between glucose disposal in response to physiological hyperinsulinemia and basal glucose and free fatty acid concentrations in healthy volunteers JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Abbasi, F., McLaughlin, T., Lamendola, C., Reaven, G. M. 2000; 85 (3): 1251-1254

    Abstract

    This study was initiated to see if defects in the ability of physiological hyperinsulinemia (approximately 60 microU/mL) to stimulate glucose uptake in healthy, nondiabetic volunteers are associated with increases in concentrations of plasma glucose and free fatty acid (FFA) when measured at basal insulin concentrations (approximately 10 microU/mL). We recruited 22 volunteers (12 women and 10 men) for these studies, with a (mean +/- SEM) body mass index of 24.8 +/- 0.5 kg/m2. Resistance to insulin-mediated glucose disposal during physiological hyperinsulinemia was determined by suppressing endogenous insulin and determining the steady-state plasma glucose (SSPG) and steady-state plasma insulin (SSPI) concentrations at the end of a 3-h infusion, period during which glucose (267 mg/m2 x min) and insulin (32 mU/m2 x min) were infused at a constant rate. Glucose, insulin and FFA concentrations were also measured in response to infusion rates of glucose (50 mg/m2 x min) and insulin (6 mU/m2 x min). The SSPI concentration (mean +/- SEM) during physiological hyperinsulinemia was 64 +/- 3 microU/mL), in contrast to 12 +/- 0.4 microU/mL during the basal insulin study. The results demonstrated a significant relationship between SSPG concentration in response to physiological hyperinsulinemia (SSPG60) and SSPG(Basal) (r = 0.57, P < 0.01) and FFA(Basal) (r = 0.73, P < 0.001). Furthermore, FFA(Basal) and SSPG(Basal) were significantly correlated (r = 0.47, P < 0.05). Comparison of the seven most insulin-resistant and seven most insulin sensitive individuals (SSPG60 values of 209 +/- 16 vs. 64 +/- 8 mg/dL) revealed that the insulin-resistant group also had significantly higher SSPG(Basal) (105 +/- 5 vs. 78 +/- 7 mg/dL, P < 0.01) and FFA(Basal) (394 +/- 91 vs. 104 +/- 41, P < 0.02) concentrations. However, random fasting plasma glucose and FFA concentrations of the two groups were not different. The results presented demonstrate that individual differences in the ability of elevated insulin concentrations to stimulate muscle glucose disposal are significantly correlated with variations in insulin regulation of plasma glucose and FFA concentrations at basal insulin concentrations.

    View details for Web of Science ID 000088387000057

    View details for PubMedID 10720071

  • Insulin regulation of plasma free fatty acid concentrations is abnormal in healthy subjects with muscle insulin resistance METABOLISM-CLINICAL AND EXPERIMENTAL Abbasi, F., McLaughlin, T., Lamendola, C., Reaven, G. M. 2000; 49 (2): 151-154

    Abstract

    This study evaluated the ability of insulin to regulate free fatty acid (FFA) concentrations in healthy nondiabetic subjects selected to be either insulin-resistant or -sensitive on the basis of insulin-mediated glucose disposal by muscle. Comparisons of steady-state plasma glucose (SSPG), insulin (SSPI), and FFA concentrations were made at the end of 3 infusion periods: (1) under basal insulin conditions (approximately 10 microU/mL), (2) in response to isoproterenol-induced stimulation of lipolysis at the same basal insulin concentration, and (3) following inhibition of isoproterenol-induced lipolysis by a 2-fold increase in the insulin concentration. The results showed that steady-state FFA concentrations were significantly higher under basal conditions (360 +/- 73 v 158 +/- 36 microEq/L, P = .02), in response to isoproterenol-induced lipolysis (809 +/- 92 v433 +/- 65 microEq/L, P = .005), and following insulin inhibition of isoproterenol-induced lipolysis (309 +/- 65 v 159 +/- 37 microEq/L, P = .06). These differences were found despite the fact that SSPG concentrations were also higher in insulin-resistant individuals during all 3 infusion periods. These results demonstrate that the ability of insulin to regulate plasma FFA concentrations is impaired in healthy subjects with muscle insulin resistance, indicating that insulin-resistant individuals share defects in the ability of insulin to stimulate muscle glucose disposal and to inhibit adipose tissue lipolysis.

    View details for Web of Science ID 000085340800002

    View details for PubMedID 10690936

  • High carbohydrate diets, triglyceride-rich lipoproteins, and coronary heart disease risk AMERICAN JOURNAL OF CARDIOLOGY Abbasi, F., McLaughlin, T., Lamendola, C., Kim, H. S., Tanaka, A., Wang, T., Nakajima, K., Reaven, G. M. 2000; 85 (1): 45-48

    Abstract

    In this study we compared the effects of variations in dietary fat and carbohydrate (CHO) content on concentrations of triglyceride-rich lipoproteins in 8, healthy, nondiabetic volunteers. The diets contained, as a percentage of total calories, either 60% CHO, 25% fat, and 15% protein, or 40% CHO, 45% fat, and 15% protein. They were consumed in random order for 2 weeks, with a 2-week washout period in between. Measurements were obtained at the end of each dietary period of plasma triglyceride, cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, remnant lipoprotein (RLP) cholesterol, and RLP triglyceride concentrations, both after an overnight fast and throughout an 8-hour period (8 A.M. to 4 P.M.) in response to breakfast and lunch. The 60% CHO diet resulted in higher (mean +/- SEM) fasting plasma triglycerides (206 +/- 50 vs 113 +/- 19 mg/dl, p = 0.03), RLP cholesterol (15 +/- 6 vs 6 +/- 1 mg/dl, p = 0.005), RLP triglyceride (56 +/- 25 vs 16 +/- 3 mg/dl, p = 0.003), and lower HDL cholesterol (39 +/- 3 vs 44 +/- 3 mg/dl, p = 0.003) concentrations, without any change in LDL cholesterol concentration. Furthermore, the changes in plasma triglyceride, RLP cholesterol, and RLP triglyceride persisted throughout the day in response to breakfast and lunch. These results indicate that the effects of lowfat diets on lipoprotein metabolism are not limited to higher fasting plasma triglyceride and lower HDL cholesterol concentrations, but also include a persistent elevation in RLPs. Given the atherogenic potential of these changes in lipoprotein metabolism, it seems appropriate to question the wisdom of recommending that all Americans should replace dietary saturated fat with CHO.

    View details for Web of Science ID 000084555000009

    View details for PubMedID 11078235

  • Fasting remnant lipoprotein cholesterol and triglyceride concentrations are elevated in nondiabetic, insulin-resistant, female volunteers JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Abbasi, F., McLaughlin, T., Lamendola, C., Yeni-Komshian, H., Tanaka, A., Wang, T., Nakajima, K., Reaven, G. M. 1999; 84 (11): 3903-3906

    Abstract

    This study was initiated to test the hypothesis that plasma concentrations of remnant lipoproteins would be higher after an overnight fast in insulin-resistant compared to insulin-sensitive volunteers. Forty-three healthy nonobese women were studied, divided into insulin-resistant (n = 21) and insulin-sensitive (n = 22) groups on the basis of their steady state plasma glucose (SSPG) concentration at the end of a 180-min infusion of octreotide acetate, insulin, and glucose. Under these conditions, steady state plasma insulin concentrations are similar in all subjects (approximately 60 microU/mL), and the higher the SSPG concentrations, the more insulin resistant the individual. By selection, mean (+/-SEM) SSPG concentrations were significantly higher (P < 0.001) in the insulin-resistant group (210 +/- 7 vs. 78 +/- 3 mg/dL). In addition, the insulin-resistant group had higher triglycerides (198 +/- 27 vs. 101 +/- 12 mg/dL; P < 0.005) and lower high density lipoprotein cholesterol (48 +/- 4 vs. 60 +/- 4 mg/dL; P < 0.05) concentrations. Finally, insulin resistance was associated with higher remnant lipoprotein particle concentrations of cholesterol (7.2 +/- 0.8 vs. 4.4 +/- 0.3; P < 0.005) and triglycerides (22.2 +/- 3.4 vs. 8.5 +/- 1.0; P < 0.001). All of these differences were seen despite the fact that the two groups were similar in terms of age and body mass index. These results identify additional abnormalities in lipoprotein metabolism that may contribute to the increased risk of coronary heart disease seen in insulin-resistant, nondiabetic subjects (syndrome X).

    View details for Web of Science ID 000083555800007

    View details for PubMedID 10566626

  • Comparison of plasminogen activator inhibitor-1 concentration in insulin-resistant versus insulin-sensitive healthy women ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY Abbasi, F., McLaughlin, T., Lamendola, C., Lipinska, I., Tofler, G., Reaven, G. M. 1999; 19 (11): 2818-2821

    Abstract

    The primary goal of this investigation was to see whether plasminogen activator inhibitor-1 (PAI-1) concentrations varied as a function of differences in insulin-mediated glucose disposal in 2 groups of healthy women matched for every other variable that might play a role in regulation of PAI-1. For this purpose, we recruited 32 healthy women, divided on the basis of their steady-state plasma glucose (SSPG) concentrations during the insulin suppression test into an insulin-resistant (SSPG=216+/-12 mg/dL, n=16) and an insulin-sensitive (94+/-6 mg/dL, n=16) group. PAI-1 antigen concentrations were significantly higher (26+/-4 versus 14+/-3 ng/mL, P<0.02) in the insulin-resistant group. In addition, fasting plasma insulin (18+/-3 versus 11+/-2 microU/mL, P<0.02) and triglyceride (160+/-19 versus 93+/-10 mg/dL, P<0.001) concentrations were higher in the insulin-resistant individuals, whereas HDL concentrations were lower (44+/-3 versus 58+/-3 mg/dL, P<0.005). However, the 2 groups were essentially identical in terms of age, menopausal status, hormone replacement therapy, body mass index (BMI), ratio of waist-to-hip girth, and blood pressure. When the experimental population was considered as 1 group, there were statistically significant correlations between PAI-1 antigen and the following variables: adjusting for differences in age and BMI, SSPG (r=0.56, P<0.001); triglyceride (r=0.39, P<0.05); and HDL cholesterol (r=-0. 65, P<0.001) concentrations. Finally, multiple regression analysis revealed the major determinants of PAI-1 to be insulin resistance, or insulin concentration, and HDL cholesterol. These results: 1) demonstrate that PAI-1 concentrations are higher in healthy, insulin-resistant women as compared with insulin-sensitive individuals, independent of differences in BMI or ratio of waist-to-hip girth; and 2) provide another mechanism by which insulin-resistant individuals are at increased thrombotic cardiovascular risk.

    View details for Web of Science ID 000083725700035

    View details for PubMedID 10559032

  • Mononuclear cell adherence to cultured endothelium is enhanced by hypertension and insulin resistance in healthy nondiabetic volunteers CIRCULATION Chen, N. G., Abbasi, F., Lamendola, C., McLaughlin, T., Cooke, J. P., Tsao, P. S., Reaven, G. M. 1999; 100 (9): 940-943

    Abstract

    This study was initiated to compare the adherence to cultured endothelial cells of mononuclear cells isolated from normotensive and hypertensive individuals.Mononuclear cell binding to endothelium was greater in patients with hypertension (32+/-1 versus 25+/-2; P<0.001) than in normal volunteers. There was a significant relationship (r=0.42, P<0. 01) between mononuclear cell binding and mean arterial pressure, independent of differences in age, sex, and body mass index. A significant relationship also existed between insulin resistance (estimated by the steady-state plasma glucose concentration during the insulin suppression test) and mononuclear cell binding in both the normotensive (r=0.86, P<0.001) and hypertensive (r=0.74, P<0. 001) groups. Furthermore, multiple regression analysis demonstrated an independent relationship (P<0.001) between mononuclear cell binding and both steady-state plasma glucose and hypertensive status.These results indicate that both hypertension and insulin resistance lead to changes in mononuclear cells that increase their adherence to cultured endothelial cells.

    View details for Web of Science ID 000082353000009

    View details for PubMedID 10468524

  • Differences in insulin resistance do not predict weight loss in response to hypocaloric diets in healthy obese women JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM McLaughlin, T., Abbasi, F., Carantoni, M., Schaaf, P., Reaven, G. 1999; 84 (2): 578-581

    Abstract

    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.

    View details for Web of Science ID 000078464000031

    View details for PubMedID 10022419

Conference Proceedings


  • Improvement in insulin sensitivity followed by ovulation and pregnancy in a woman with polycystic ovary syndrome who was treated with rosiglitazone Cataldo, N. A., Abbasi, F., McLaughlin, T. L., Lamendola, C., Reaven, G. M. ELSEVIER SCIENCE INC. 2001: 1057-1059

    Abstract

    To determine the metabolic and reproductive effectiveness of rosiglitazone in polycystic ovary syndrome (PCOS).Case report.Academic clinical practice and General Clinical Research Center.A 25-year-old woman with PCOS.Rosiglitazone maleate, 4 mg daily for 5 months until conception.Insulin sensitivity by steady-state plasma glucose technique; serum androgens, progesterone, and hCG; and pelvic ultrasound images.Rosiglitazone treatment for 5 months improved insulin sensitivity, lowered serum free testosterone, and resulted in spontaneous ovulation and conception.Rosiglitazone is a promising insulin sensitizer for treatment of PCOS. Clinical trials are warranted.

    View details for Web of Science ID 000172083900034

    View details for PubMedID 11704136

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