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ABSTRACT: Insulin-mediated glucose disposal varies severalfold in apparently healthy individuals, and approximately one-third of the most insulin resistant of these individuals is at increased risk to develop various adverse clinical syndromes. Since direct measurements of insulin sensitivity are not practical in a clinical setting, several surrogate estimates of insulin action have been proposed, including fasting plasma insulin (FPI) concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) calculated by a formula employing fasting plasma glucose (FPG) and FPI concentrations. The objective of this study was to compare FPI as an estimate of insulin-mediated glucose disposal with values generated by HOMA-IR in 758 apparently healthy nondiabetic individuals. Measurements were made of FPG, FPI, triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) concentrations, and insulin-mediated glucose uptake was quantified by determining steady-state plasma glucose (SSPG) concentration during the insulin suppression test. FPI and HOMA-IR were highly correlated (r = 0.98, P < 0.001). The SSPG concentration also correlated to a similar degree (P < 0.001) with FPI (r = 0.60) and HOMA-IR (r = 0.64). Furthermore, the relationship between FPI and TG (r = 0.35) and HDL-C (r = -0.40) was comparable to that between HOMA-IR and TG (r = 0.39) and HDL-C (r = -0.41). In conclusion, FPI and HOMA-IR are highly correlated in nondiabetic individuals, with each estimate accounting for ~40 % of the variability (variance) in a direct measure of insulin-mediated glucose disposal. Calculation of HOMA-IR does not provide a better surrogate estimate of insulin action, or of its associated dyslipidemia, than measurement of FPI.
Acta Diabetologica 02/2013; · 2.78 Impact Factor
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ABSTRACT: BACKGROUND: Two direct measurements of peripheral insulin sensitivity are the M value derived from the euglycemic, hyperinsulinemic clamp (EC) and the steady-state plasma glucose (SSPG) concentration derived from the insulin suppression test (IST). Prior work suggests that these measures are highly correlated, but the agreement between them is unknown. To determine the agreement between SSPG and M and to develop transformation equations to convert SSPG to M and vice versa, we directly compared these two measurements in the same individuals. METHODS: A total of 15 nondiabetic subjects (9 women and 6 men) underwent both an EC and a modified version of the IST within a median interval of 5days. We performed standard correlation metrics of the two measures and developed transformation regression equations for the two measures. RESULTS: The mean±SD age of the subjects was 57±7years and body mass index, 27.7±3.9kg/m(2). The median (interquartile range) SSPG concentration was 6.7 (5.1, 9.8) mmol/L and M value, 49.6 (28.9, 64.2) μmol/min/kg-LBM. There was a highly significant correlation between SSPG and M (r=-0.87, P <0.001). The relationship was best fit by regression models with exponential/logarithmic functions (R(2)=0.85). Bland-Altman plots demonstrated an excellent agreement between these measures of insulin action. CONCLUSION: The SSPG and M are highly related measures of insulin sensitivity and the results provide the means to directly compare the two measurements.
Metabolism: clinical and experimental 11/2012; · 2.59 Impact Factor
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ABSTRACT: Aim: The aim of this study was to test the hypothesis that body mass index (BMI) and waist circumference (WC) associate to a comparable degree with insulin resistance and cardiometabolic risk factors in South Asians. Methods: We measured blood pressure and fasting glucose, insulin, triglyceride, high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hs-CRP), and fibrinogen and calculated the homeostasis model assessment of insulin resistance (HOMA-IR) in a community-based sample of 923 nondiabetic South Asians. Results: BMI and WC were highly correlated in both genders (r = 0.82 and 0.87). The relationship between BMI and values of blood pressure, glucose, insulin, HOMA-IR, triglyceride, HDL-C, hs-CRP, and fibrinogen was comparable to that between WC and these variables. Fasting insulin and HOMA-IR correlated most strongly with BMI (r = 0.49 to 0.56) and WC (r = 0.52 to 0.59). Conclusion: These results show that BMI and WC associate to a comparable degree with estimates of insulin resistance and related metabolic abnormalities in South Asians.
Diabetes & Vascular Disease Research 01/2012; 9(4):296-300. · 2.12 Impact Factor
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ABSTRACT: Studies on the relationship between regional fat and insulin resistance yield mixed results. Our objective was to determine whether regional fat distribution, independent of obesity, is associated with insulin resistance.
Subjects included 115 healthy, overweight/moderately obese adults with body mass index (BMI) 25-36.9 kg/m(2) who met predetermined criteria for being insulin resistant (IR) or insulin sensitive (IS) based on the modified insulin suppression test. Computerized tomography was used to quantify visceral adipose tissue (VAT), sc adipose tissue (SAT), and thigh adipose tissue. Fat mass in each depot was compared according to IR/IS group, adjusting for BMI and sex.
Despite nearly identical mean BMI in the IR vs. IS groups, VAT and %VAT were significantly higher in the IR group, whereas SAT, %SAT, and thigh sc fat were significantly lower. In logistic regression analysis, each sd increase in VAT increased the odds of being IR by 80%, whereas each increase in SAT decreased the odds by 48%; each increase in thigh fat decreased the odds by 59% and retained significance after adjusting for other depots. When grouped by VAT tertile, IS vs. IR individuals had significantly more SAT. There was no statistically significant interaction between sex and these relationships.
These data demonstrate that after adjustment for BMI and VAT mass, sc abdominal and thigh fat are protective for insulin resistance, whereas VAT, after adjustment for SAT and BMI, has the opposite effect. Whether causal in nature or a marker of underlying pathology, these results clarify that regional distribution of fat-favoring sc depots is associated with lower risk for insulin resistance.
The Journal of clinical endocrinology and metabolism 08/2011; 96(11):E1756-60. · 6.50 Impact Factor
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ABSTRACT: The objective was to compare relationships between insulin-mediated glucose uptake and surrogate estimates of insulin action, particularly those using fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations. Insulin-mediated glucose uptake was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test in 455 nondiabetic subjects. Fasting TG, HDL-C, glucose, and insulin concentrations were measured; and calculations were made of the following: (1) plasma concentration ratio of TG/HDL-C, (2) TG × fasting glucose (TyG index), (3) homeostasis model assessment of insulin resistance, and (4) insulin area under the curve (insulin-AUC) during a glucose tolerance test. Insulin-AUC correlated most closely with SSPG (r ∼ 0.75, P < .001), with lesser but comparable correlations between SSPG and TG/HDL-C ratio, TyG index, homeostasis model assessment of insulin resistance, and fasting TG and insulin (r ∼ 0.60, P < .001). Calculations of TG/HDL-C ratio and TyG index correlated with SSPG concentration to a similar degree, and the relationships were comparable to estimates using fasting insulin. The strongest relationship was between SSPG and insulin-AUC.
Metabolism: clinical and experimental 05/2011; 60(12):1673-6. · 2.59 Impact Factor
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ABSTRACT: Several surrogate estimates have been used to define relationships between insulin action and pancreatic β-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 β-cell function in individuals whose fasting plasma glucose (FPG) was <7.0 mmol/L (126 mg/dL).
We determined 2 indices of insulin secretion [homeostasis model assessment of β-cell function (HOMA-β) 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.
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-β) 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 about β-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 β-cell function has been obtained.
Clinical Chemistry 02/2011; 57(4):627-32. · 7.91 Impact Factor
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ABSTRACT: Prehypertension is considered to be associated with increased cardiovascular disease (CVD), and some data suggest that insulin resistance is common in this group. The goal of this study was to quantify insulin action by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test in apparently healthy individuals with prehypertension (n=126) and to elucidate the relationship between insulin action and CVD risk.We found a marked heterogeneity in insulin sensitivity in the prehypertension group, and when we divided the population into insulin-sensitive, insulin-resistant and intermediate groups, there were significant (p<0.01) increases in plasma glucose and triglyceride concentrations and decreases in high-density lipoprotein cholesterol concentrations with progressive degrees of insulin resistance. These data show that at least one-third of patients with prehypertension are insulin resistant, display the accompanying metabolic abnormalities, and merit enhanced surveillance and intensive efforts at therapeutic intervention to prevent CVD.
Diabetes & Vascular Disease Research 01/2011; 8(1):43-6. · 2.12 Impact Factor
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ABSTRACT: Roux-en-Y gastric bypass surgery (RYGB) has been associated with a hypoglycemic syndrome characterized by postprandial hypoglycemia and hyperinsulinemia. The syndrome is believed to occur due to insulin hypersecretion from either pancreatic beta-cell hyperplasia or hyperfunction.
Eight RYGB patients with hypoglycemic syndrome had insulin secretion rates determined during a 240-min graded intravenous glucose infusion. They were compared to 34 nondiabetic, nonsurgical individuals who were divided based on their insulin sensitivity status as measured by the insulin suppression test: insulin-sensitive (n = 8), insulin intermediate (n = 7), and insulin-resistant (n = 19).
RYGB patients had insulin concentrations and HOMA-IR similar to the insulin-sensitive reference group. In addition, integrated insulin secretion rates were comparable to the insulin-sensitive group and significantly lower than the insulin intermediate (p <or= 0.046) and insulin-resistant groups (p <or= 0.001). Pancreatic beta-cell sensitivity to glucose (slope relating glucose and ISR) was lowest in the RYGB group (p <or= 0.04).
Patients with hypoglycemic syndrome post-RYGB do not have generalized hypersecretion of insulin and appear to have appropriate insulin secretion rate in response to intravenous glucose.
Obesity Surgery 08/2010; 20(8):1110-6. · 3.29 Impact Factor
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ABSTRACT: 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.
Hepatology 07/2010; 52(1):38-46. · 11.66 Impact Factor
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ABSTRACT: It has recently been suggested that a low urine pH be added to the abnormalities linked to insulin resistance. This conclusion is based on the finding of a low urine pH in individuals with clinical syndromes associated with insulin resistance and not on studies in which a direct measure of insulin sensitivity was shown to be significantly related to differences in urine pH.
To address this issue, we quantified insulin-mediated glucose uptake (IMGU) by using the insulin suppression test in 96 apparently healthy, nondiabetic individuals and defined its relation to fasting urine pH.
Urine samples were collected and analyzed from a cohort of healthy subjects within a narrow body mass index range who were recruited to determine insulin sensitivity.
There was an approximate 6-fold variation in values for IMGU in this population, with no relation to urine pH (r = 0.02). Furthermore, there was no relation between body mass index, as a surrogate estimate of insulin resistance, and urine pH (r = 0.06).
On the basis of these findings, we question the view that a low urine pH be added to the abnormalities linked to insulin resistance in low-risk populations.
American Journal of Clinical Nutrition 03/2010; 91(3):586-8. · 6.67 Impact Factor
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ABSTRACT: The goal of this study was to compare methods used to quantify the effect of rosiglitazone (RSG) on insulin secretory function, particularly estimates based on changes in fasting plasma glucose and insulin concentration vs daylong insulin responses to meals. To do this, we compared these measures of insulin secretion before and 3 months after RSG treatment in insulin-resistant individuals, subdivided into nondiabetic subjects (n = 29) and patients with type 2 diabetes mellitus (2DM) (n = 22). Insulin resistance was quantified by determining the steady-state plasma glucose concentration during the insulin suppression test and insulin secretory function by homeostasis model assessment of β-cell function (HOMA-β) and the total integrated daylong plasma insulin responses to mixed meals (insulin area under the curve). Baseline fasting and daylong plasma glucose concentrations were higher (P < .001) in patients with 2DM, associated with lower HOMA-β values (P < .001). However, neither fasting nor daylong insulin concentrations after mixed meals differed in the 2 groups. Insulin sensitivity improved (P < .001) after RSG administration, with decreases of 31% ± 23% and 21% ± 14% in steady-state plasma glucose concentration in nondiabetic and diabetic subjects, respectively. Although fasting and daylong plasma glucose and insulin concentrations fell (P < .001) in both groups of RSG-treated individuals, HOMA-β decreased in nondiabetic subjects and did not change in those with 2DM. In conclusion, RSG administration improved insulin sensitivity in both groups, associated with lower fasting and daylong glucose concentrations. Fasting and daylong insulin concentrations were also lower in both groups of RSG-treated subjects, but the values of HOMA-β indicated either a decrease (nondiabetics) or no change (diabetics) in insulin secretory function. These results suggest that measurements of HOMA-β may not provide a complete view of insulin secretory function, either when comparing diabetic with nondiabetic individuals or when assessing the response to RSG treatment in insulin-resistant individuals.
Metabolism: clinical and experimental 03/2010; 60(1):57-62. · 2.59 Impact Factor
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ABSTRACT: Second generation antipsychotics (SGAs) can increase weight gain and weight-induced insulin resistance. Recent studies have suggested weight-independent effects of certain SGAs on insulin resistance; however the magnitude of these effects and the relationship between BMI and insulin resistance in patients on SGAs are not established. To evaluate, the relationship between body mass index (BMI) and insulin resistance in 54 patients being stably treated with olanzapine (n=19), risperidone (n=16), or aripiprazole (n=19) was compared with data from a large reference population (n=201) not on SGAs. Insulin resistance was directly quantified by measuring the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. The relationship between BMI and SSPG was similar between the SGA (r=0.58) and the reference population (r=0.50). When SSPG was standardized based on expected values for the reference population, patients on olanzapine had a higher degree of insulin resistance (mean z-score+/-SD, 0.68+/-0.9) than expected for level of BMI compared with those on aripiprazole (-0.25+/-1) and risperidone (-0.3+/-0.9), F(2,51)=6.28 (p=0.004). Thus, olanzapine group was 0.76 SD above the reference population or in the 78 percentile for insulin resistance. SSPG was correlated with fasting plasma insulin concentration (0.78 (0.64-0.87), p<0.001) but not fasting glucose concentration (0.15 (-0.13-0.40), p=0.29). In conclusion, BMI contributes a quarter to a third of the variance in insulin resistance in the SGA population similar to the reference population. Olanzapine also appears to have an independent effect on insulin resistance that is above and beyond obesity.
Journal of psychiatric research 12/2009; 44(8):493-8. · 3.72 Impact Factor
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Alice Liu,
Tracey McLaughlin,
Teresa Liu,
Arthur Sherman,
Gail Yee, Fahim Abbasi,
Cindy Lamendola,
John Morton,
Samuel W Cushman,
Gerald M Reaven,
Philip S Tsao
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ABSTRACT: We recently identified differences in abdominal subcutaneous adipose tissue (SAT) from insulin-resistant (IR) as compared to obesity-matched insulin sensitive individuals, including accumulation of small adipose cells, decreased expression of cell differentiation markers, and increased inflammatory activity. This study was initiated to see if these changes in SAT of IR individuals were present in omental visceral adipose tissue (VAT); in this instance, individuals were chosen to be IR but varied in degree of adiposity. We compared cell size distribution and genetic markers in SAT and VAT of IR individuals undergoing bariatric surgery.
Eleven obese/morbidly obese women were IR by the insulin suppression test. Adipose tissue surgical samples were fixed in osmium tetroxide for cell size analysis via Beckman Coulter Multisizer. Quantitative real-time polymerase chain reaction for genes related to adipocyte differentiation and inflammation was performed.
While proportion of small cells and expression of adipocyte differentiation genes did not differ between depots, inflammatory genes were upregulated in VAT. Diameter of SAT large cells correlated highly with increasing proportion of small cells in both SAT and VAT (r = 0.85, p = 0.001; r = 0.72, p = 0.01, respectively). No associations were observed between VAT large cells and cell size variables in either depot. The effect of body mass index (BMI) on any variables in both depots was negligible.
The major differential property of VAT of IR women is increased inflammatory activity, independent of BMI. The association of SAT adipocyte hypertrophy with hyperplasia in both depots suggests a primary role SAT may have in regulating regional fat storage.
Obesity Surgery 09/2009; 19(11):1564-73. · 3.29 Impact Factor
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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.
Obesity Surgery 07/2009; 19(11):1550-6. · 3.29 Impact Factor
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ABSTRACT: This study compared the effects of administering rosiglitazone (RSG) vs pioglitazone (PIO) on cardiovascular disease risk factors in insulin-resistant, nondiabetic individuals with no apparent disease. Twenty-two nondiabetic, apparently healthy individuals, classified as being insulin resistant on the basis of a steady-state plasma glucose concentration of at least 10 mmol/L during the insulin suppression test, were treated with either RSG or PIO for 3 months. Measurements were made before and after drug treatment of weight; blood pressure; fasting and daylong glucose, insulin, and free fatty acid (FFA) levels; and lipid and lipoprotein concentrations. Insulin sensitivity (steady-state plasma glucose concentration) significantly improved in both treatment groups, associated with significant decreases in daylong plasma concentrations of glucose, insulin, and FFA. Diastolic blood pressure fell somewhat in both groups, and this change reached significance in those receiving PIO. Improvement in lipid metabolism was confined to the PIO-treated group, signified by a significant decrease in plasma triglyceride concentration, whereas triglyceride concentration did not decline in the RSG-treated group, and these individuals also had increases in total (P = .047) and low-density lipoprotein cholesterol (P = .07). In conclusion, RSG and PIO appear to have comparable abilities to improve insulin sensitivity and lower daylong glucose, insulin, and FFA concentrations in nondiabetic, insulin-resistant individuals. However, despite these similarities, their effects on lipoprotein metabolism seem to be quite different, with beneficial effects confined to PIO-treated individuals.
Metabolism: clinical and experimental 04/2009; 58(3):373-8. · 2.59 Impact Factor
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ABSTRACT: Although moderate alcohol consumption has been associated with a decrease in plasma insulin concentrations, relatively few studies have been conducted to evaluate the effect of alcohol on insulin sensitivity, particularly in nondiabetic, insulin-resistant individuals. Because enhanced insulin sensitivity could contribute to the reported association between moderate alcohol consumption and reduced risk of heart disease and diabetes, we believed it is important to address this issue. Consequently, we evaluated the ability of moderate alcohol consumption to improve insulin sensitivity, as measured by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test, in 20 nondiabetic, insulin-resistant individuals. Measurements were made of SSPG, glucose, insulin, and lipoprotein concentrations before and after consuming 30 g of alcohol for 8 weeks, either as vodka (n = 9) or red wine (n = 11). The SSPG concentrations (insulin resistance) decreased by approximately 8% in the total group (P = .08), and high-density lipoprotein cholesterol concentration increased by a mean of 0.09 mmol/L (P = .02). Trends were similar in individuals who consumed vodka or red wine. Men tended to have greater decline in SSPG and increase in high-density lipoprotein cholesterol compared with women. There were no other metabolic changes in fasting plasma glucose, insulin, and triglyceride concentrations. These data demonstrate that 8 weeks of moderate alcohol consumption had minimal impact on enhancing insulin sensitivity in nondiabetic, insulin-resistant individuals, raising questions as to the role, if any, of improved insulin sensitivity in the purported clinical benefits associated with moderate alcohol consumption.
Metabolism: clinical and experimental 04/2009; 58(3):387-92. · 2.59 Impact Factor
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ABSTRACT: There is evidence that the subgroup of patients with essential hypertension who are also insulin resistant is at increased risk of cardiovascular disease (CVD). We are unaware of the frequency of insulin resistance in patients with essential hypertension as well as the CVD risk in this subgroup of patients. This analysis was aimed at providing the prevalence of insulin resistance and associated CVD risk factors in treated and untreated patients with essential hypertension.
The study population consisted of 126 patients with hypertension: 56 untreated and 70 in a stable treatment program. Body mass index (BMI), blood pressure, plasma glucose and insulin responses to an oral glucose challenge, lipid and lipoprotein concentrations, and steady-state plasma glucose (SSPG) concentration during the insulin suppression test were measured. Insulin resistance was defined operationally as a SSPG concentration >180 mg/dl.
Demographic characteristics and metabolic CVD risk factors were comparable in both groups, with 30-50% of both treated and untreated patients having abnormalities of all risk factors measured. Approximately 50% of patients met the criteria for insulin resistance in both groups, and the prevalence of abnormal CVD risk factors in this group was increased two to threefold as compared to the other half of the subjects.
Approximately 50% of patients with essential hypertension, both treated and untreated, appear to be insulin resistant, and CVD risk factors are greatly accentuated in this subset of patients.
American Journal of Hypertension 09/2008; 22(1):106-11. · 3.18 Impact Factor
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ABSTRACT: The goal of this study was to compare the impact of differences in waist circumference (WC) defined according to the International Diabetes Federation (IDF) and the Adult Treatment Panel III (ATP III) and body mass index (BMI) on cardiovascular disease risk factors in 402 apparently healthy volunteers of European ancestry. Consequently, measurements were made of the WC, BMI, blood pressure, glucose, and lipid components of metabolic syndrome (MS) and insulin-mediated glucose uptake. Subjects were divided according to WC (IDF and ATP III criteria) and by normal weight, overweight, or obesity using BMI, and comparisons were made of the effect of these different indexes of adiposity on cardiovascular disease risk factors. The results indicated that WC and BMI significantly correlated (p <0.001) and were associated with differences in insulin-mediated glucose uptake to a similar degree in men (r = 0.57 and r = 0.59) and women (r = 0.53 and r = 0.52). Prevalences of MS were essentially identical irrespective of the measure of WC used (ATP III vs IDF), as were metabolic characteristics of those classified using IDF or ATP III criteria. Cardiovascular disease risk factor status did not vary substantially when subjects were divided on the basis of WC or BMI. In conclusion, prevalences of MS or cardiovascular disease risk factors did not vary as a function of differences in IDF and ATP III criteria for WC. BMI identified individuals at increased cardiovascular disease risk as effectively as determination of WC.
The American Journal of Cardiology 08/2008; 102(1):40-6. · 3.37 Impact Factor
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ABSTRACT: 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.
The American Journal of Cardiology 08/2008; 102(1):64-9. · 3.37 Impact Factor
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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.
Metabolism: clinical and experimental 08/2008; 57(8):1108-14. · 2.59 Impact Factor
