Statins Are Associated With Increased Insulin Resistance and Secretion.

Objective: Statin treatment reduces the risk of atherosclerotic cardiovascular disease but is associated with a modest increased risk of type 2 diabetes, especially in those with insulin resistance or prediabetes. Our objective was to determine the physiological mechanism for the increased type 2 diabetes risk. Approach and Results: We conducted an open-label clinical trial of atorvastatin 40 mg daily in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline. The co-primary outcomes were changes at 10 weeks versus baseline in insulin resistance as assessed by steady-state plasma glucose during the insulin suppression test and insulin secretion as assessed by insulin secretion rate area under the curve (ISRAUC) during the graded-glucose infusion test. Secondary outcomes included glucose and insulin, both fasting and during oral glucose tolerance test. Of 75 participants who enrolled, 71 completed the study (median age 61 years, 37% women, 65% non-Hispanic White, median body mass index, 27.8 kg/m2). Atorvastatin reduced LDL (low-density lipoprotein)-cholesterol (median decrease 53%, P<0.001) but did not change body weight. Compared with baseline, atorvastatin increased insulin resistance (steady-state plasma glucose) by a median of 8% (P=0.01) and insulin secretion (ISRAUC) by a median of 9% (P<0.001). There were small increases in oral glucose tolerance test glucoseAUC (median increase, 0.05%; P=0.03) and fasting insulin (median increase, 7%; P=0.01). Conclusions: In individuals without type 2 diabetes, high-intensity atorvastatin for 10 weeks increases insulin resistance and insulin secretion. Over time, the risk of new-onset diabetes with statin use may increase in individuals who become more insulin resistant but are unable to maintain compensatory increases in insulin secretion.

Adapting to insulin resistance in obesity: role of insulin secretion and clearance.

AIMS/HYPOTHESIS: The aim of this study was to quantify the relative contributions of increased insulin secretion rate (ISR) and decreased insulin clearance rate (ICR) in the compensatory hyperinsulinaemia characteristic of insulin-resistant individuals without diabetes. METHODS: Obese (BMI ≥30 kg/m2) individuals without diabetes (n = 91) were identified from a registry of volunteers. Volunteers underwent the following measurements: oral glucose tolerance; insulin resistance (steady-state plasma glucose [SSPG] concentration during the insulin suppression test [IST]); ISR (using the graded glucose infusion test [GGIT]); and ICR (using the IST and GGIT). Participants were stratified into tertiles based on SSPG concentration: SSPG-1(insulin-sensitive); SSPG-2 (intermediate); and SSPG-3 (insulin-resistant). RESULTS: There were no differences in BMI and waist circumference among the SSPG tertiles. Serum alanine aminotransferase concentrations were higher in the SSPG-2 and SSPG-3 groups compared with the SSPG-1 group (p = 0.02). Following an oral glucose challenge, there was a progressive increase in the total integrated insulin response from the most insulin-sensitive to the most insulin-resistant tertiles (p < 0.001). Following intravenous glucose, the SSPG-3 group had significantly greater integrated glucose (median [interquartile range], 32.9 [30.8-36.3] mmol/l × h) and insulin responses (1711 [1476-2223] mmol/l × h) compared with the SSPG-1 group (30.3 [28.8-32.9] mmol/l × h, p = 0.04, and 851 [600-1057] pmol/l × h, p < 0.001, respectively). Furthermore, only the SSPG-3 group had significant changes in both ISR and ICR (p < 0.001). In the SSPG-2 group, only the ICR was significantly decreased compared with the SSPG-1 group. Therefore, ICR progressively declined during the IST with increasing insulin resistance (SSPG-1, 0.48 [0.41-0.59]; SSPG-2, 0.43 [0.39-0.50]; SSPG-3, 0.34 [0.31-0.40]). CONCLUSIONS/INTERPRETATION: While both increases in ISR and decreases in ICR compensate for insulin resistance, decreases in ICR may provide the first adaptation to decreased insulin sensitivity.

Cardiometabolic Risk in South Asian Inhabitants of California: Hypertriglyceridemic Waist vs Hypertriglyceridemic Body Mass Index.

OBJECTIVE: Hypertriglyceridemic waist (HTG-waist), an increased waist circumference (WC) with an elevated triglyceride (TG) concentration, can identify increased cardiometabolic risk in apparently healthy individuals. Since WC and BMI are highly correlated, we examined whether an HTG-BMI would be as effective as an HTG-waist in identifying cardiometabolic risk in apparently healthy South Asians. DESIGN SETTING AND PARTICIPANTS: In this cross-sectional study, we classified South Asian women (n=1156) and men (n=1842) without diabetes mellitus as having an HTG-waist (TG ≥150 mg/dL and a WC ≥80 cm in women or ≥ 90 cm in men) and an HTG-BMI (TG ≥150 mg/dL and a BMI ≥23 kg/m²). OUTCOME MEASURES: We measured cardiometabolic risk factors, including blood pressure and fasting lipid profile, glucose, insulin, fibrinogen, and high-sensitivity C-reactive protein. RESULTS: An HTG-waist was present in 670 individuals, of whom 648 (97%) had an HTG-BMI. The cardiometabolic profile was significantly more adverse in those in whom an HTG-waist was present vs absent; and the same was true when individuals with an HTG-BMI were compared with those without. CONCLUSIONS: Essentially every individual with an HTG-waist also had an HTG-BMI. An HTG-BMI identified cardiometabolic risk as effectively as an HTG-waist in a population composed entirely of South Asians.

Low circulating 25-hydroxyvitamin D concentrations are associated with defects in insulin action and insulin secretion in persons with prediabetes.

BACKGROUND: Individuals with prediabetes mellitus (PreDM) and low circulating 25-hydroxyvitamin D [25(OH)D] are at increased risk of type 2 diabetes mellitus (T2DM). OBJECTIVE: We aimed to determine whether low 25(OH)D concentrations are associated with defects in insulin action and insulin secretion in persons with PreDM. METHODS: In this cross-sectional study, we stratified 488 nondiabetic subjects as having PreDM or normal fasting glucose (NFG) and a 25(OH)D concentration ≤20 ng/mL (deficient) or >20 ng/mL (sufficient). We determined insulin resistance by steady state plasma glucose (SSPG) concentration and homeostasis model assessment of insulin resistance (HOMA-IR) and insulin secretion by homeostasis model assessment of ß-cell function (HOMA-ß). We compared insulin resistance and secretion measures in PreDM and NFG groups; 25(OH)D-deficient and 25(OH)D-sufficient groups; and PreDM-deficient, PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups, adjusting for age, sex, race, body mass index, multivitamin use, and season. RESULTS: In the PreDM group, mean SSPG concentration and HOMA-IR were higher and mean HOMA-ß was lower than in the NFG group (P < 0.001 for all comparisons). In the 25(OH)D-deficient group, mean SSPG concentration was higher (P < 0.001), but neither mean HOMA-IR nor HOMA-ß was significantly different from that in the 25(OH)D-sufficient group. In the PreDM-deficient subgroup, mean (95% CI) SSPG concentration was higher (P < 0.01) than in the PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups [192 (177-207) mg/dL vs. 166 (155-177) mg/dL, 148 (138-159) mg/dL, and 136 (127-144) mg/dL, respectively]. Despite greater insulin resistance, mean HOMA-ß was not significantly higher in the PreDM-deficient subgroup than in the PreDM-sufficient, NFG-deficient, and NFG-sufficient subgroups [98 (85-112) vs. 91 (82-101), 123 (112-136), and 115 (106-124), respectively]. CONCLUSION: Subjects with PreDM and low circulating 25(OH)D concentrations are the subgroup of nondiabetic individuals who are the most insulin resistant and have impaired ß-cell function, attributes that put them at enhanced risk of T2DM.

Use of plasma triglyceride/high-density lipoprotein cholesterol ratio to identify increased cardio-metabolic risk in young, healthy South Asians.

BACKGROUND & OBJECTIVES: Prevalence of insulin resistance and associated dyslipidaemia [high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations] are increased in South Asian individuals; likely contributing to their increased risk of type-2 diabetes and cardiovascular disease. The plasma concentration ratio of TG/HDL-C has been proposed as a simple way to identify apparently healthy individuals at high cardio-metabolic risk. This study was carried out to compare the cardio-metabolic risk profiles of high-risk South Asian individuals identified by an elevated TG/HDL-C ratio versus those with a diagnosis of the metabolic syndrome. METHODS: Body mass index, waist circumference, blood pressure, and fasting plasma glucose, insulin, TG, and HDL-C concentrations were determined in apparently healthy men (n=498) and women (n=526). The cardio-metabolic risk profile of "high risk" individuals identified by TG/HDL-C ratios in men (≥ 3.5) and women (≥2.5) was compared to those identified by a diagnosis of the metabolic syndrome. RESULTS: More concentrations of all cardio-metabolic risk factors were significantly higher in "high risk" groups, identified by either the TG/HDL-C ratio or a diagnosis of the metabolic syndrome. TG, HDL-C, and insulin concentrations were not significantly different in "high risk" groups identified by either criterion, whereas plasma glucose and blood pressure were higher in those with the metabolic syndrome. INTERPRETATION & CONCLUSIONS: Apparently healthy South Asian individuals at high cardio-metabolic risk can be identified using either the TG/HDL-C ratio or the metabolic syndrome criteria. The TG/HDL-C ratio may be used as a simple marker to identify such individuals.

Do differences in waist circumference modify the relationships among body mass index, insulin resistance, and related cardiometabolic risk factors in apparently healthy women?

OBJECTIVE: The aims of the study were to (1) compare the cardiometabolic risk profile between insulin-resistant and non-insulin-resistant women within similar body mass indexes (BMIs) and waist circumference (WC) groupings and (2) test the hypothesis that measurements of BMI are not inferior to WC in identifying insulin resistance. METHODS: The sample consisted of 899 women without known cardiovascular disease or diabetes. BMI was used to divide participants in normal (<25.0 kg/m(2)), overweight (≥25-29.9 kg/m(2)), and obese (≥30.0 kg/m(2)) subgroups, and waist circumference ≥88 cm was used to identify women with or without abdominal obesity. The 25% of the population with highest fasting insulin concentrations was classified as insulin resistant. BMI, WC, blood pressure, and fasting plasma glucose, insulin, triglyceride, and high-density lipoprotein cholesterol concentrations were compared using analysis of covariance (ANCOVA). The relationships between obesity and insulin resistance were analyzed using univariate, multivariate, and logistic regression. RESULTS: Triglyceride and glucose concentrations were higher and high-density lipoprotein cholesterol concentrations lower in the insulin-resistant group in each BMI category, as was the case when comparing by abdominal obesity. In the univariate analysis, correlations between obesity and the individual cardiometabolic risk factor were significant but weak. In multivariate analysis including both indices, only body mass independently predicted insulin resistance. CONCLUSION: Insulin-resistant women were at greater cardiometabolic risk, irrespective of adiposity category. Obesity contributed to a modest variability in insulin resistance, and abdominal obesity does not add to the ability of BMI to predict insulin resistance.

Plasma triglyceride/HDL-cholesterol ratio, insulin resistance, and cardiometabolic risk in young adults.

Studies in mature adults suggest that the plasma concentration ratio of triglyceride (TG)/HDL-cholesterol (HDL-C) provides a simple way to identify apparently healthy individuals who are insulin resistant (IR) and at increased cardiometabolic risk. This study extends these observations by examining the clinical utility of the TG/HDL-C ratio and the metabolic syndrome (MetS) in 2,244 healthy college students (17-24 years old) of Mexican Mestizo ancestry. The TG/HDL-C ratio separating the 25% with the highest value was used to identify IR and increased cardiometabolic risk. Cardiometabolic risk factors were more adverse in men and women whose TG/HDL-C ratios exceeded 3.5 and 2.5, respectively, and approximately one third were identified as being IR. The MetS identified fewer individuals as being IR, but their risk profile was accentuated. In conclusion, both a higher TG/HDL-C ratio and a diagnosis of the MetS identify young IR individuals with an increased cardiometabolic risk profile. The TG/HDL-C ratio identified a somewhat greater number of "high risk" subjects, whereas the MetS found a group whose risk profile was somewhat magnified. These findings suggest that the TG/HDL-C ratio may serve as a simple and clinically useful approach to identify apparently healthy, young individuals who are IR and at increased cardiometabolic risk.

Risk for obstructive sleep apnea in obese, nondiabetic adults varies with insulin resistance status.

PURPOSE: Obstructive sleep apnea (OSA) is an increasingly common sleep disorder, especially among obese adults. Early identification of adults at risk for OSA would be of substantial benefit; however, the magnitude of the obesity epidemic requires that screening be performed judiciously. The study's aim was to utilize questionnaires that assess OSA risk and symptoms to test the hypothesis that the most insulin-resistant subset of obese individuals is at highest risk for OSA. METHODS: Nondiabetic, overweight to obese volunteers underwent direct quantification of insulin sensitivity by measuring steady-state plasma glucose concentrations during the insulin suppression test. Insulin-sensitive and insulin-resistant individuals were administered the Berlin and STOP questionnaires to determine OSA risk status, and Epworth Sleepiness Scale (ESS) to evaluate daytime sleepiness. Fasting insulin and lipid/lipoprotein measurements were performed. RESULTS: Insulin-mediated glucose disposal differed threefold (p < 0.001) between equally obese, insulin-resistant (n = 22) and insulin-sensitive (n = 14) individuals, associated with higher fasting insulin and triglyceride and lower high-density lipoprotein cholesterol (HDL-C) concentrations in insulin-resistant individuals. Fourteen (64 %) insulin-resistant as compared with 2 (14 %) insulin-sensitive individuals were found to be at high risk for OSA by both questionnaires (p < 0.01). Whereas half of insulin-resistant individuals met the ESS criteria for excessive daytime sleepiness, only one insulin-sensitive individual did (p = 0.011). CONCLUSIONS: High risk for OSA and excessive daytime sleepiness is prevalent among the insulin-resistant subgroup of obese individuals. Surrogate estimates of insulin resistance based on fasting insulin, triglycerides, and/or HDL-C can be used to help identify those obese adults who would benefit most from OSA screening and referral for polysomnography.

Estimates of insulin secretory function in apparently healthy volunteers vary as a function of how the relevant variables are quantified.

BACKGROUND: Several surrogate estimates have been used to define relationships between insulin action and pancreatic ß-cell function in healthy individuals. Because it is unclear how conclusions about insulin secretory function depend on specific estimates used, we evaluated the effect of different approaches to measurement of insulin action and secretion on observations of pancreatic ß-cell function in individuals whose fasting plasma glucose (FPG) was <7.0 mmol/L (126 mg/dL). METHODS: We determined 2 indices of insulin secretion [homeostasis model assessment of ß-cell function (HOMA-ß) and daylong insulin response to mixed meals], insulin action [homeostasis model assessment of insulin resistance (HOMA-IR) and steady-state plasma glucose (SSPG) concentration during the insulin suppression test], and degree of glycemia [fasting plasma glucose (FPG) and daylong glucose response to mixed meals] in 285 individuals with FPG <7.0 mmol/L. We compared the relationship between the 2 measures of insulin secretion as a function of the measures of insulin action and degree of glycemia. RESULTS: Assessment of insulin secretion varied dramatically as a function of which of the 2 methods was used and which measure of insulin resistance or glycemia served as the independent variable. For example, the correlation between insulin secretion (HOMA-ß) and insulin resistance varied from an r value of 0.74 (when HOMA-IR was used) to 0.22 (when SSPG concentration was used). CONCLUSIONS: Conclusions about ß-cell function in nondiabetic individuals depend on the measurements used to assess insulin action and insulin secretion. Viewing estimates of insulin secretion in relationship to measures of insulin resistance and/or degree of glycemia does not mean that an unequivocal measure of pancreatic ß-cell function has been obtained.

Comparison of surrogate and direct measurement of insulin resistance in chronic hepatitis C virus infection: impact of obesity and ethnicity.

UNLABELLED: Studies using surrogate estimates show high prevalence of insulin resistance in hepatitis C infection. This study prospectively evaluated the correlation between surrogate and directly measured estimates of insulin resistance and the impact of obesity and ethnicity on this relationship. Eighty-six nondiabetic, noncirrhotic patients with hepatitis C virus (age = 48 +/- 7 years, 74% male, 44% white, 22% African American, 26% Latino, 70% genotype 1) were categorized into normal-weight (body mass index [BMI] < 25, n = 30), overweight (BMI = 25-29.9, n = 38), and obese (BMI > or = 30, n = 18). Insulin-mediated glucose uptake was measured by steady-state plasma glucose (SSPG) concentration during a 240-minute insulin suppression test. Surrogate estimates included: fasting glucose and insulin, glucose/insulin, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), insulin (I-AUC) and glucose (G-AUC) area under the curve during oral glucose tolerance test, and the Belfiore and Stumvoll indexes. All surrogate estimates correlated with SSPG, but the magnitude of correlation varied (r = 0.30-0.64). The correlation coefficients were highest in the obese. I-AUC had the highest correlation among all ethnic and weight groups (r = 0.57-0.77). HOMA-IR accounted for only 15% of variability in SSPG in the normal weight group. The common HOMA-IR cutoff of < or =3 to define insulin resistance had high misclassification rates especially in the overweight group independent of ethnicity. HOMA-IR > 4 had the lowest misclassification rate (75% sensitivity, 88% specificity). Repeat HOMA-IR measurements had higher within-person variation in the obese (standard deviation = 0.77 higher than normal-weight, 95% confidence interval = 0.25-1.30, P = 0.005). CONCLUSION: Because of limitations of surrogate estimates, caution should be used in interpreting data evaluating insulin resistance especially in nonobese, nondiabetic patients with HCV.

Why Syndrome X? From Harold Himsworth to the insulin resistance syndrome.

Although the concept of Syndrome X was introduced in the Banting Medal address of 1988 (Reaven, 1988), the notion that led to its genesis had started approximately 50 years earlier. In this short history, an attempt will be made to trace the two paths of scientific discovery that were formally merged in New Orleans in 1988 to form the scientific foundation of Syndrome X. In addition, the developments in the last 16 years that have led from the notion of Syndrome X to the broader concept of an Insulin Resistance Syndrome (IRS) will be briefly summarized.

Apelin is necessary for the maintenance of insulin sensitivity.

The recently discovered peptide apelin is known to be involved in the maintenance of insulin sensitivity. However, questions persist regarding its precise role in the chronic setting. Fasting glucose, insulin, and adiponectin levels were determined on mice with generalized deficiency of apelin (APKO). Additionally, insulin (ITT) and glucose tolerance tests (GTT) were performed. To assess the impact of exogenously delivered apelin on insulin sensitivity, osmotic pumps containing pyroglutamated apelin-13 or saline were implanted in APKO mice for 4 wk. Following the infusion, ITT/GTTs were repeated and the animals euthanized. Soleus muscles were harvested and homogenized in lysis buffer, and insulin-induced Akt phosphorylation was determined by Western blotting. Apelin-13 infusion and ITTs/GTTs were also performed in obese diabetic db/db mice. To probe the underlying mechanism for apelin's effects, apelin-13 was also delivered to cultured C2C12 myotubes. 2-[3H]deoxyglucose uptake and Akt phosphorylation were assessed in the presence of various inhibitors. APKO mice had diminished insulin sensitivity, were hyperinsulinemic, and had decreased adiponectin levels. Soleus lysates had decreased insulin-induced Akt phosphorylation. Administration of apelin to APKO and db/db mice resulted in improved insulin sensitivity. In C2C12 myotubes, apelin increased glucose uptake and Akt phosphorylation. These events were fully abrogated by pertussis toxin, compound C, and siRNA knockdown of AMPKalpha1 but only partially diminished by LY-294002 and not at all by L-NAME. We conclude that apelin is necessary for the maintenance of insulin sensitivity in vivo. Apelin's effects on glucose uptake and Akt phosphorylation are in part mediated by a G(i) and AMPK-dependent pathway.

Cardiorespiratory Fitness, Body Mass Index, and Markers of Insulin Resistance in Apparently Healthy Women and Men.

BACKGROUND: Insulin resistance may be present in healthy adults and is associated with poor health outcomes. Obesity is a risk factor for insulin resistance, but most obese adults do not have insulin resistance. Fitness may be protective, but the association between fitness, weight, and insulin resistance has not been studied in a large population of healthy adults. METHODS: A cross-sectional analysis of cardiorespiratory fitness, body mass index, and markers of insulin resistance was performed. Study participants were enrolled at the Cooper Clinic in Dallas, Texas. The analysis included 19,263 women and 48,433 men with no history of diabetes or cardiovascular disease. Cardiorespiratory fitness was measured using exercise treadmill testing. Impaired fasting glucose (100-125 mg/dL) and elevated fasting triglycerides (≥150 mg/dL) were used as a markers of insulin resistance. RESULTS: Among individuals with normal weight, poor fitness was associated with 2.2-fold higher odds of insulin resistance in women (1.4-3.6; P = .001) and 2.8-fold higher odds in men (2.1-3.6; P <.001). The impact of fitness remained significant for overweight and obese individuals, with the highest risk group being the unfit obese. Among obese women, the odds ratio for insulin resistance was 11.0 for fit women (8.7-13.9; P <.001) and 20.3 for unfit women (15.5-26.5; P <.001). Among obese men, the odds ratio for insulin resistance was 7.4 for fit men (6.7-8.2; P < .001) and 12.9 for unfit men (11.4-14.6; P < .001). CONCLUSIONS: Independent of weight, poor fitness is associated with risk of insulin resistance. Obese individuals, particularly women, may benefit from the greatest absolute risk reduction by achieving moderate fitness.

A1 adenosine receptor: role in diabetes and obesity.

Adenosine mediates its diverse effects via four subtypes (A(1), A(2A), A(2B) and A(3)) of G-protein-coupled receptors. The A(1) adenosine receptor (A(1)AR) subtype is the most extensively studied and is well characterized in various organ systems. The A(1)ARs are highly expressed in adipose tissue, and endogenous adenosine has been shown to tonically activate adipose tissue A(1)ARs. Activation of the A(1)ARs in adipocytes reduces adenylate cyclase and cAMP content and causes inhibition of lipolysis. The role of A(1)ARs in lipolysis has been well characterized by using several selective A(1)AR agonists as well as A(1)AR knockout mice. However, the contribution of A(1)ARs to the regulation of lipolysis in pathological conditions like insulin resistance, diabetes and dyslipidemia, where free fatty acids (FFA) play an important role, has not been well characterized. Pharmacological agents that reduce the release of FFA from adipose tissue and thus the availability of circulating FFA have the potential to be useful for insulin resistance and hyperlipidemia. Toward this goal, several selective and efficacious agonists of the A(1)ARs are now available, and some have entered early-phase clinical trials; however, none have received regulatory approval yet. Here we review the existing knowledge on the role of A(1)ARs in insulin resistance, diabetes and obesity, and the progress made in the development of A(1)AR agonists as antilipolytic agents, including the challenges associated with this approach.

Plasma glucose concentration 60 min post oral glucose load and risk of type 2 diabetes and cardiovascular disease: Pathophysiological implications.

AIM: The aim of this study was to gain insight into the pathophysiological significance of elevated plasma glucose concentrations (mmol/L) 60 min post oral glucose load in apparently healthy individuals. METHODS: Comparison of resistance to insulin action and associated cardio-metabolic risk factors in 490 apparently healthy persons, subdivided into those with a plasma glucose concentration 60 min following a 75-g oral glucose challenge of <8.6 versus ⩾8.6. RESULTS: Insulin resistance was significantly greater in persons with normal glucose tolerance whose 60-min glucose concentration was ⩾8.6, associated with higher blood pressure, plasma concentrations of glucose, insulin, triglyceride and lower high-density lipoprotein cholesterol concentrations. Similar differences were seen in persons with impaired fasting glucose, but not in those with impaired glucose tolerance or both impaired fasting glucose and impaired glucose tolerance. The group whose 60-min glucose was <8.6 (n = 318) contained primarily persons with normal glucose tolerance (88%), whereas the majority of those whose 60-min value was ⩾8.6 (n = 172) had prediabetes (59%) and in particular combined impaired fasting glucose and impaired glucose tolerance. CONCLUSION: Plasma glucose concentration of ⩾8.6 mmol/L 60 min post oral glucose identifies higher proportions of combined impaired fasting glucose and impaired glucose tolerance individuals as well as normal glucose tolerance and impaired fasting glucose individuals with a more adverse cardio-metabolic profile, contributing to observed increased overall risk of type 2 diabetes and other metabolic diseases.

Impact of race/ethnicity on insulin resistance and hypertriglyceridaemia.

OBJECTIVE: Insulin sensitivity affects plasma triglyceride concentration and both differ by race/ethnicity. The purpose of this study was to provide a comprehensive assessment of the variation in insulin sensitivity and its relationship to hypertriglyceridaemia between five race/ethnic groups. RESEARCH DESIGN AND METHODS: In this cross-sectional study, clinical data for 1025 healthy non-Hispanic White, Hispanic White, East Asian, South Asian and African American individuals were analysed. Insulin-mediated glucose disposal (a direct measure of peripheral insulin sensitivity) was measured using the modified insulin suppression test. Statistical analysis was performed using analysis of co-variance. RESULTS: Of the study participants, 63% were non-Hispanic White, 9% were Hispanic White, 11% were East Asian, 11% were South Asian and 6% were African American. Overall, non-Hispanic Whites and African Americans displayed greater insulin sensitivity than East Asians and South Asians. Triglyceride concentration was positively associated with insulin resistance in all groups, including African Americans. Nevertheless, for any given level of insulin sensitivity, African Americans had the lowest triglyceride concentrations. CONCLUSION: Insulin sensitivity, as assessed by a direct measure of insulin-mediated glucose disposal, and its relationship to triglyceride concentration vary across five race/ethnic groups. Understanding these relationships is crucial for accurate cardiovascular risk stratification and prevention.

Insulin resistance: the link between obesity and cardiovascular disease.

Insulin-mediated glucose disposal varies at least sixfold in apparently healthy individuals. The adverse effect of decreases in the level of physical fitness on insulin sensitivity is comparable to the untoward impact of excess adiposity, with each accounting for approximately 25% of the variability of insulin action. It is the loss of insulin sensitivity that explains why obese individuals are more likely to develop cardiovascular disease, but not all overweight/obese individuals are insulin resistant. At a clinical level, it is important to identify those overweight individuals who are also insulin resistant and to initiate the most intensive therapeutic effort in this subgroup. Finally, it appears that the adverse impact of overall obesity, as estimated by body mass index, is comparable to that of abdominal obesity, as quantified by waist circumference.

Comparison of three treatment approaches to decreasing cardiovascular disease risk in nondiabetic insulin-resistant dyslipidemic subjects.

The efficacy of fenofibrate (FEN), rosiglitazone (RSG), or a calorie-restricted diet (CRD) to reduce cardiovascular disease risk was compared in 37 overweight/obese insulin-resistant nondiabetic subjects. Insulin sensitivity, fasting lipids and lipoproteins, and postprandial plasma glucose, insulin, free fatty acid, and triglycerides were measured before and after 3 months of treatment with FEN, RSG, or CRD. Weight decreased in the CRD group, but did not change significantly after treatment with either drug. Insulin sensitivity improved significantly in the CRD- and RSG-treated groups, but to a greater extent in those administered RSG, without a significant difference comparing FEN treatment with the CRD. Total cholesterol was significantly lower after FEN and CRD treatment. Fasting plasma triglycerides decreased significantly in the FEN- and CRD-treated groups, but postprandial concentrations decreased in only FEN-treated subjects. Significant decreases in postprandial glucose and insulin were seen in only the RSG- and CRD-treated groups. FEN administration improved dyslipidemia in these subjects without changing insulin sensitivity, whereas insulin sensitivity was enhanced in RSG-treated patients without improvement in dyslipidemia. Weight loss in the CRD group led to improvements in both insulin sensitivity and dyslipidemia, but the change in the former was less than in RSG-treated patients, and improvement in lipid metabolism not as great as with FEN. In conclusion, there did not appear to be 1 therapeutic intervention that effectively treated all metabolic abnormalities present in these patients at greatly increased risk of cardiovascular disease.

Does the association of the triglyceride to high-density lipoprotein cholesterol ratio with fasting serum insulin differ by race/ethnicity?

BACKGROUND: The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been reported to be as closely correlated with insulin resistance as is the fasting serum insulin concentration (FSI), and therefore it is seen as a clinically useful way to identify the concomitant presence of insulin resistance and dyslipidemia. However, conflicting findings exist for the association of the TG/HDL-C ratio with FSI by race/ethnicity. METHODS: The associations of FSI concentration, serum triglyceride concentrations, and HDL-C were analyzed using log-binomial regression analyses and receiver operating characteristic (ROC) curve analysis among nondiabetic adults (n = 2652, aged > or = 20 years, 51.2% men) in the United States. RESULTS: After adjustment for potential confounding effects, the prevalence ratio of hyperinsulinemia was 2.16 (95% confidence interval [CI], 1.74 to 2.08) when using a single cutoff point of 3.5, and 2.23 (95% CI, 1.83 to 2.72) when using race/ethnicity-specific cutoff points of 3.0 for non-Hispanic whites and Mexican Americans and 2.0 for non-Hispanic blacks for the TG/HDL-C ratio. The area under the ROC curve of the TG/HDL-C ratio for predicting hyperinsulinemia was 0.77 (95% CI, 0.74 to 0.79), 0.75 (95% CI, 0.69 to 0.77), and 0.74 (95% CI, 0.69 to 0.76) for non-Hispanic whites, non-Hispanic blacks, and Mexican Americans, respectively. CONCLUSION: There was a significant association between the TG/HDL-C ratio and FSI among three major racial/ethnic groups in the United States. Our results add further support to the notion that the TG/HDL-C ratio may be a clinically simple and useful indicator for hyperinsulinemia among nondiabetic adults regardless of race/ethnicity.