Pioglitazone decreases postprandial accumulation of remnant lipoproteins in insulin-resistant smokers

Background:  Fasting hypertriglyceridaemia has been reported to occur commonly in cigarette smokers and is thought to increase cardiovascular disease (CVD) risk in these individuals. More recently, it has been suggested that an increase in non-fasting triglycerides, rather than fasting hypertriglyceridaemia, is an independent CVD risk factor.
Methods:  In this study, we divided 24 smokers into insulin-resistant (IR) and insulin-sensitive (IS) groups by determining their steady-state plasma glucose concentrations during the insulin suppression test and compared fasting and daylong postprandial accumulation of total triglycerides and remnant lipoprotein (RLP) concentrations, before and after 3 months of pioglitazone (PIO) administration.
Results:  The two groups were similar in age, body mass index, race and gender distribution, but differed dramatically in insulin sensitivity. Baseline fasting and postprandial triglyceride, RLP cholesterol and RLP triglyceride concentrations were significantly higher in the IR smokers (p = 0.01 to <0.01). Insulin sensitivity and both fasting and postprandial triglyceride and RLP triglyceride levels decreased significantly (p = 0.05 to <0.01) in PIO-treated IR smokers, without any significant increase in weight. In contrast, there were no significant changes in either insulin sensitivity or fasting and postprandial triglyceride, RLP cholesterol and RLP triglyceride levels in PIO-treated IS smokers.
Conclusions:  The postprandial accumulation of RLP particles is increased in the IR subset of smokers and is likely to contribute to the increased CVD risk in these individuals. Furthermore, PIO administration provides a possible therapeutic approach to decreasing postprandial lipaemia and CVD risk in IR smokers who are unwilling or unable to stop smoking.     

The relationship between plasma adiponectin concentration and insulin resistance is altered in smokers

CONTEXT: Low plasma adiponectin concentrations in smokers may contribute to the adverse consequences that occur in these individuals. OBJECTIVE: The objective of the study was to define the relationship among smoking, plasma adiponectin concentrations, insulin resistance, and inflammation. DESIGN: This was a cross-sectional, observational study with a 2 x 2 factorial design and a prospective longitudinal arm. SETTING: The study was conducted at a general clinical research center. PARTICIPANTS: 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: 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. RESULTS: 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). CONCLUSIONS: 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.     

Prevalence of insulin resistance and associated cardiovascular disease risk factors among normal weight, overweight, and obese individuals

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.     

Insulin resistance and compensatory hyperinsulinemia: the key player between cigarette smoking and cardiovascular disease?

Hyperinsulinemia, dyslipidemia, and endothelial dysfunction are characteristic findings in insulin-resistant individuals, and all of these abnormalities have been identified as increasing cardiovascular disease (CVD) risk. Smokers tend to be relatively insulin resistant, hyperinsulinemic, and dyslipidemic, with evidence of endothelial dysfunction, as compared with nonsmokers, and recent epidemiologic data have suggested that CVD in smokers is primarily seen in those individuals who also have the characteristic findings of insulin resistance. Based on these observations, it is argued that insulin resistance and its consequences represent a major mechanistic link between cigarette smoking and CVD. It is also postulated that the enhanced CVD risk in smokers, resulting from hyperinsulinemia, abnormalities of lipoprotein metabolism, and endothelial dysfunction, will primarily be present in those smokers who are insulin resistant. As a corollary, it is suggested that CVD risk in individuals who cannot, or will not, stop smoking can be reduced by therapeutic efforts aimed at attenuating the adverse effects of insulin resistance and its consequences.     

Plasma asymmetric dimethylarginine concentrations are elevated in obese insulin-resistant women and fall with weight loss

CONTEXT: Plasma asymmetric dimethylarginine (ADMA) concentrations are higher in apparently healthy, insulin-resistant (IR) individuals and decrease in response to thiazolidenedione treatment. OBJECTIVE: 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. OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSION: 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.     

Effect of moderate alcoholic beverage consumption on insulin sensitivity in insulin-resistant, nondiabetic individuals

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.     

Comparison of two methods using plasma triglyceride concentration as a surrogate estimate of insulin action in nondiabetic subjects: triglycerides × glucose versus triglyceride/high-density lipoprotein cholesterol

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.     

Impact of cigarette smoking on the relationship between body mass index and insulin: Longitudinal observation from the Bogalusa Heart Study

Objectives

Despite the inverse association between cigarette smoking and body mass index (BMI), it is unknown whether the effect of smoking on insulin is mediated through decreased BMI. This study aims to examine the temporal relationship between BMI and insulin, the impact of smoking on this relationship and the mediation effect of BMI on the association between smoking and insulin levels.

Methods

The longitudinal cohort consisted of 1121 adults (807 white and 314 black participants, mean age, 42.0 years at follow‐up) for whom BMI and fasting insulin were measured twice, with an average follow‐up period of 17.1 years. Cross‐lagged panel and mediation analysis models were used to examine the temporal relationship between BMI and insulin, and the mediation effect of BMI on the smoking‐insulin association.

Results

Smoking was inversely associated with insulin (regression coefficient, ?0.073; P = .015 at baseline and ?0.121; P < .001 at follow‐up), adjusting for age, race and gender. After additional adjustment for follow‐up periods, the cross‐lagged path coefficient from BMI to insulin (β, 0.226; P < .001) was significantly greater than that from insulin to BMI (β, ?0.029; P = .208), with P < .001 for the difference. The path coefficient from BMI to insulin was significantly greater in non‐smokers (β, 0.273; P < .001) than in smokers (β, 0.122; P = .046), with P = .013 for the difference. The mediation effect of BMI on the smoking‐insulin association was estimated at 53.4% (P = .030) at baseline and 58.7% (P < .001) at follow‐up.

Conclusions

These findings suggest that cigarette smoking has a significant impact on the one‐directional relationship from BMI to insulin. The insulin‐lowering effect of smoking is predominantly mediated through decreased BMI as the result of smoking.     

Adiposity indices in the prediction of metabolic abnormalities associated with cardiovascular disease in non-diabetic adults

Background and Aims

The prevalence of insulin resistance and cardiovascular disease (CVD) increases with degree of obesity. Whether measurements of generalized and abdominal obesity differ in the ability to predict changes associated with increased CVD risk is widely debated. We compared the prevalence of metabolic abnormalities in 275 women and 204 men stratified by categories of body mass index (BMI) and waist circumference (WC), and assessed the ability of these adiposity indices in combination with metabolic risk variables to predict insulin resistance.

Methods and Results

Healthy, non-diabetic volunteers underwent measurements of BMI, WC, blood pressure, fasting plasma glucose (FPG), lipoprotein concentrations, and direct quantification of insulin-mediated glucose uptake. Insulin resistance was defined as the top tertile of steady-state plasma glucose (SSPG) concentrations. BMI and WC were highly correlated (P < 0.001) in both women and men. Abnormal SSPG and triglyceride concentrations were associated with increasing adiposity by either index in both genders. Among women, abnormal FPG and high density lipoprotein cholesterol (HDL-C) concentrations were associated with increasing BMI and WC. In men, abnormal HDL-C was associated with increasing BMI only. Elevated systolic blood pressure (SBP) was associated with increasing BMI in both genders. The odds of insulin resistance were greatest in women with elevated FPG and triglycerides (4.5-fold). In men, the best predictors were BMI and SBP, and WC and HDL-C (3-fold).

Conclusion

BMI is at least comparable to WC in stratifying individuals for prevalence of metabolic abnormalities associated with increased CVD risk and predicting insulin resistance.     

Metabolic changes following sibutramine-assisted weight loss in obese individuals: role of plasma free fatty acids in the insulin resistance of obesity.

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.     

Effect of cigarette smoking on insulin resistance risk

ObjectivesSmoking is one of the main risk factors for cardiovascular disease (CVD). The mechanism(s) of the effects of smoking on CVD are not clearly understood; however, a number of atherogenic characteristics, such as insulin resistance have been reported. We aim to investigate the effects of cigarette smoking on insulin resistance and to determine the correlation between this parameter with smoking status characteristics.Study designThis study was conducted on 138 non-smokers and 162 smokers aged respectively 35.6 ± 16.0 and 38.5 ± 21.9 years. All subjects are not diabetic.MethodsFasting glucose was determined by enzymatic methods and insulin by chemiluminescence method. Insulin resistance (IR) was estimated using the Homeostasis Model of Assessment equation: HOMA-IR = [fasting insulin (mU/L) × fasting glucose (mmol/L)]/22.5. IR was defined as the upper quartile of HOMA-IR. Values above 2.5 were taken as abnormal and reflect insulin resistance.ResultsCompared to non-smokers, smokers had significantly higher levels of fasting glucose, fasting insulin and HOMA-IR index. These associations remained significant after adjustment for confounding factors (age, gender, BMI and alcohol consumption). A statistically significant association was noted between the smoking status parameters, including both the number of cigarettes smoked/day and the duration of smoking, and fasting insulin levels as well for HOMA-IR index. Among smokers, we noted a positive correlation between HOMA-IR index and both plasma thiocyanates and urinary cotinine.ConclusionOur results show that smokers have a high risk to developing an insulin resistance and hyperinsulinemia, compared with a matched group of non-smokers, and may help to explain the high risk of cardiovascular diseases in smokers.     

Insulin resistance is associated with a modest increase in inflammation in subcutaneous adipose tissue of moderately obese women

Aims/hypothesis  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. Methods  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. Results  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. Conclusions/interpretation  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. Trial registration ClinicalTrials.gov NCT00285844 Funding The study was funded by grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and by the NIDDK Intramural Research Program.     

Plasma homocysteine concentrations in healthy volunteers are not related to differences in insulin-mediated glucose disposal.

This study was initiated to test the hypothesis that plasma homocysteine concentrations are increased in insulin resistant individuals. For this purpose, the relationship between insulin resistance, as assessed by the steady-state plasma glucose (SSPG) concentration during the insulin suppression test, and fasting plasma homocysteine concentration was defined in 55 healthy volunteers. The results indicated that homocysteine concentrations did not vary as a function of SSPG concentrations (r = 0.02, P = 0.88). Furthermore, mean (+/- S.E.M.) plasma homocysteine concentrations were similar (8.2+/-0.4 vs. 8.7+/-0.7 micromol/l) in individuals classified as being either insulin sensitive (SSPG <100 mg/dl) or insulin resistant (SSPG >180 mg/dl). On the other hand, SSPG concentration was significantly correlated with fasting plasma insulin (r = 0.58, P<0.001), triglycerides (r = 0.34, P<0.05), and HDL-cholesterol (r = -0.36, P = 0.04) concentrations. These data strongly suggest that the increased risk of atherosclerosis associated with increased plasma homocysteine concentrations is unrelated to insulin resistance and/or the metabolic abnormalities associated with it.     

Acute effects of cigarette smoking on insulin resistance and arterial stiffness in young adults

BackgroundIt is unclear whether changes in insulin sensitivity or arterial stiffness in cigarette smokers could explain the link between cigarette smoking and diabetes mellitus. The purpose of the study was to evaluate the acute effects of cigarette smoking on insulin resistance and arterial stiffness in a cohort of young healthy adults.MethodsMetabolic risk components, hemodynamic parameters, plasma nitrite/nitrate and high-sensitivity C-reactive protein (hsCRP) levels, were compared between smokers and age- and gender-matched controls (non-smokers). In smokers, these levels were determined 8-h following cigarette abstinence and an hour after smoking.ResultsOne hundred nineteen smokers and age-matched non-smokers (mean age, 32 years; 83% men) were included in this study. Compared with non-smokers, smokers had a significantly higher number of abnormal metabolic risk components, HOMA-IR index and total nitrite/nitrate levels. There were no differences in brachial/central blood pressure, augmentation index and hsCRP between smokers and non-smokers. An hour after smoking, smokers had significantly higher levels of HOMA-IR, total nitrite/nitrate, hsCRP and heart rate compared with baseline levels. By contrast, brachial/central blood pressure and augmentation index were unchanged after cigarette smoking. Baseline vascular and insulin resistance status predicted the extent of rise in the HOMA-IR and augmentation indices acutely after cigarette smoking (adjusted R² 0.358 and 0.124, p < 0.001 respectively).ConclusionsIndividuals with more advanced vascular damage and insulin resistance are vulnerable to the acute effects of cigarette smoking.     

The Impact of Cigarette Smoking on 24‐Hour Blood Pressure,Inflammatory and Hemostatic Activity,and Cardiovascular Risk in Japanese Hypertensive Patients

The aim of the study was to assess the impact of current smoking on 24‐hour blood pressure (BP) and inflammatory and hemostatic activity and thereby the incidence of cardiovascular disease (CVD) in Japanese hypertensive patients. A total of 810 hypertensive patients (mean age 72 years; 38% men) were prospectively followed‐up (2799 person‐years). During the follow‐up, 66 cases of CVD occurred (stroke, 55; myocardial infarction, 7; both, 4). At baseline, the current smokers (n=166) had higher levels of high‐sensitivity C‐reactive protein (hs‐CRP) (0.21 mg/dL vs 0.14 mg/dL) and plasminogen activator inhibitor‐1 (PAI‐1) (46.1 ng/mL vs 37.8 ng/mL; both P=.001), but not of 24‐hour BP, compared with nonsmokers. Using a Cox regression analysis, current smoking was independently associated with an increased risk of CVD (hazard ratio [HR], 2.6; P<.01), and the risk was substantially higher in women (HR, 6.1; P<.001) than in men (HR, 1.4; P=.41). The CVD risk of current smokers was magnified when it was accompanied with high hs‐CRP (highest quartile range, ≥0.40 mg/L) or PAI‐1 levels (≥58.9 ng/mL) compared with that in smokers with low hs‐CRP or PAI‐1 levels (both P<.05). Among hypertensive patients, current smokers had increased risk of CVD events, and the increase was more prominent when accompanied by circulatory inflammatory and hemostatic abnormalities. J Clin Hypertens (Greenwich). 2012;00:00–00. ©2012 Wiley Periodicals, Inc.     

Does menthol attenuate the effect of bupropion among African American smokers?

Background African Americans have higher tobacco‐related morbidity and mortality and are more likely to smoke menthol cigarettes than their white counterparts. This study examined differences between African American menthol and non‐menthol smokers in smoking characteristics and cessation. Methods The study sample consisted of 600 African American smokers enrolled in a clinical trial that assessed the efficacy of sustained‐release bupropion for smoking cessation. Menthol (n = 471) and non‐menthol (n = 129) smokers were compared on smoking‐related characteristics and abstinence rates at 6 weeks and 6 months. Results Menthol smokers were younger (41.2 versus 52.9 years), more likely to be female (73.7% versus 56.6%) and more likely to smoke their first cigarette within 30 minutes of waking up (81.7% versus 69.8%) compared to non‐menthol smokers (all P < 0.01). Cigarette taste (50% versus 40%, P = 0.054) was rated non‐significantly higher by menthol smokers. Seven‐day point‐prevalence abstinence from smoking at 6 weeks were 28% and 42% (P = 0.006) and at 6 months were 21% and 27% (P = 0.21) for menthol and non‐menthol smokers, respectively. At 6 weeks follow‐up, stepwise logistic regression revealed that among those younger than 50 years, non‐menthol smokers were more likely to quit smoking (odds ratio = 2.0; 95% CI = 1.03–3.95) as were those who received bupropion (odds ratio = 2.12; 95% CI = 1.32–3.39). Conclusion African American menthol smokers had lower smoking cessation rates after 6 weeks of treatment with bupropion‐SR, thereby putting menthol smokers at greater risk from the health effects of smoking. Lower overall cessation rates among African Americans menthol smokers may partially explain ethnic differences in smoking‐related disease risks.     

Plasma adiponectin concentrations do not increase in association with moderate weight loss in insulin-resistant, obese women

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.     

The relationship between insulin resistance and dyslipidaemia in cigarette smokers

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These data suggest that the dyslipidaemia previously attributed to smoking occurs primarily in those smokers who are also insulin resistant.     

Cigarette smoking increases the mean platelet volume in elderly patients with risk factors for atherosclerosis

Summary To study the effects of cigarette smoking and atherosclerosis on platelet size, we measured the mean platelet volume (MPV) and other platelet parameters in 142 elderly smokers and nonsmokers with or without atherosclerotic risk factors. The MPV and the platelet count were highest and their inverse correlation was strongest in the atherosclerotic smokers (r= 0.54, P < 0.05) when compared with the nonsmoking and non-atherosclerotic groups. A 10% decrease of MPV was found in 8 smoking subjects in the atherosclerotic group, who successfully discontinued smoking (P < 0.05). These results suggest that smoking may increase platelet consumption in atherosclerotic vessels and that subsequently megakaryocytes are activated to produce larger platelets, which are more active. Thus, an increase in MPV due to smoking may also contribute to the acceleration of atherosclerosis and should be considered as a risk factor for atherosclerotic disease.     

Coronary artery disease risk predicted by insulin resistance, plasma lipids, and hypertension in people without diabetes

BACKGROUND: It has been shown that insulin resistance syndrome, including glucose intolerance, dyslipidemia, and hypertension, is frequently associated with coronary artery disease (CAD). However, their relative contributions and predictive power in the development of CAD are still unclear, particularly in persons without diabetes. METHOD: We examined these risk factors between 96 patients without diabetes but with angiographically documented CAD and 96 age-, sex-, and body mass index-matched healthy control subjects. Fasting plasma lipoprotein, glucose, and insulin concentrations in response to a 75-g oral glucose tolerance test were determined, and insulin sensitivity was measured by the insulin suppression test. RESULTS: Patients with CAD had significantly higher values of fasting glucose, glucose and insulin responses to oral glucose tolerance test, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride and decreased high-density lipoprotein (HDL) cholesterol concentrations compared with those of healthy people (P < 0.02-0.001). Although the steady-state plasma insulin values were similar in both groups, the steady-state plasma glucose (SSPG) concentrations were significantly higher in patients with CAD (12.2+/-0.4 versus 8.1+/-0.4 mmol/L, P < 0.001) compared with healthy subjects. When HDL < 0.9 mmol/L, LDL cholesterol > or = 4.1 mmol/L, triglyceride > or = 2.3 mmol/L, SSPG > or = 10.5 mmol/L, and presence of hypertension were defined as separate risk factors for CAD, significantly higher odds-ratio values were observed in patients with CAD compared with healthy people. From logistic multiple regression analysis, SSPG was the strongest risk, followed by lowered HDL cholesterol, elevated triglyceride and LDL cholesterol, and hypertension, to predict CAD. These 5 factors accounted for 36% of total risk for development of CAD in persons without diabetes. CONCLUSIONS: Patients without diabetes with CAD have abnormal glucose metabolism, hyperinsulinemia, and insulin resistance. Degree of insulin resistance (SSPG values), plasma lipid values, and history of hypertension together accounted for one third of all risk for CAD, although degree of insulin resistance was the strongest risk factor.