Should obesity be blamed for the high prevalence rates of hypertension in black South African women?

Hypertension is highly prevalent in South Africa, resulting in high stroke mortality rates. Since obesity is very common among South African women, it is likely that obesity contributes to the hypertension prevalence. The aims were to determine whether black African women have higher blood pressures (BPs) than Caucasian women, and whether obesity is related to their cardiovascular risk. African (N=102) and Caucasian (N=115) women, matched for age and body mass index, were included. Correlations between obesity (total body fat, abdominal obesity and peripheral fat) and cardiovascular risk markers (haemodynamic parameters, lipids, inflammatory markers, prothrombotic factors, adipokines, HOMA-IR (homoeostasis model assessment insulin resistance)) were compared between the ethnic groups (adjusted for age, smoking, alcohol and physical activity). Comparisons between low- and high-BP groups were also made for each ethnic group. Results showed that African women had higher BP (P<0.01) with increased peripheral vascular resistance. Surprisingly, African women showed significantly weaker correlations between obesity measures and cardiovascular risk markers when compared to Caucasian women (specifically systolic BP, arterial resistance, cardiac output, fibrinogen, plasminogen activator inhibitor-1, leptin and resistin). Interestingly, the latter risk markers were also not significantly different between low- and high-BP African groups. African women, however, presented significant correlations of obesity with triglycerides, C-reactive protein and HOMA that were comparable to the Caucasian women. Although urban African women have higher BP than Caucasians, their obesity levels are weakly related to traditional cardiovascular risk factors compared to Caucasian women. The results, however, suggest a link with the development of insulin resistance.     

Asymmetric dimethylarginine is associated with parameters of glucose metabolism in Caucasian but not in African women from South Africa.

AIM: Ethnic differences in obesity and obesity related disorders prompted us to search for possible contributors. The impact of the novel cardiovascular risk factor asymmetric dimethylarginine (ADMA) has been never determined in the African population. The present observational study aimed to compare ADMA levels between healthy African (102) and Caucasian women (115) from South Africa, and its impact on glucose metabolism. METHODS: All participants underwent an oral glucose tolerance test with measurements of glucose, insulin, C-peptide, proinsulin and free fatty acids before and after 30, 60, 90, 120 minutes. Fasting serum ADMA was measured by ELISA assay and obesity was determined by anthropometry. RESULTS: Serum ADMA did not differ between the ethnic groups. After stratification according to ADMA quartiles Caucasian women in the upper quartile had significantly higher body mass index and waist circumference as well as elevated insulin resistance, insulin, C-peptide and proinsulin levels with no differences in serum glucose compared to women in the lowest quartile. There was a significant stronger postchallenge insulin response in Caucasian women of the upper quartile. No differences were found in African women. CONCLUSIONS: Despite similar ADMA levels in both ethnic groups ADMA was positively correlated with parameters of glucose metabolism in the Caucasian but not in the African women from South Africa.     

Leptin is favourably associated with vascular function in obese Caucasians, but not in obese Africans

The comparison of the associations between chronically elevated leptin levels and cardiovascular function in obese Africans and Caucasians has not yet been determined. Therefore, the aim of this study was to compare leptin's associations with cardiovascular function in obese African and obese Caucasian women to determine whether leptin's associations differ between these two groups. This study consisted of two case-case control studies. The first study included a sample of 102 apparently healthy African women and the second, 115 apparently healthy Caucasian women. All lean and obese subjects were selected from each study. The Finometer apparatus was used to obtain a more elaborate cardiovascular profile. Serum leptin levels, insulin levels and the lipid profile were determined. Stroke volume (SV) and cardiac output (CO) were significantly (P< or =0.01) elevated in both obese African and Caucasian groups compared to their lean controls. Total peripheral resistance (TPR) was significantly decreased and arterial compliance (C(W)) significantly increased in both obese African and Caucasian groups. In the obese Caucasian group, diastolic blood pressure (DBP) was significantly (P< or =0.01) lower, SV and C(W) significantly higher (P< or =0.01) and TPR significantly lower compared to the age, body mass index (BMI), and leptin-matched obese African group. After adjusting for age and BMI, leptin correlated negatively with DBP (P< or =0.05; r=-0.33) and TPR (P< or =0.05; r=-0.36) in the obese Caucasian group, but not in the obese African group. Even though leptin levels were similar in obese African and Caucasian women, leptin is favourably associated with vascular function in obese Caucasians, but not in obese Africans.     

Biopsychosocial Correlates of Binge Eating Disorder in Caucasian and African American Women with Obesity in Primary Care Settings

This study examined racial differences in eating‐disorder psychopathology, eating/weight‐related histories, and biopsychosocial correlates in women (n = 53 Caucasian and n = 56 African American) with comorbid binge eating disorder (BED) and obesity seeking treatment in primary care settings. Caucasians reported significantly earlier onset of binge eating, dieting, and overweight, and greater number of times dieting than African American. The rate of metabolic syndrome did not differ by race. Caucasians had significantly elevated triglycerides whereas African Americans showed poorer glycaemic control (higher glycated haemoglobin A1c [HbA1c]), and significantly higher diastolic blood pressure. There were no significant racial differences in features of eating disorders, depressive symptoms, or mental and physical health functioning. The clinical presentation of eating‐disorder psychopathology and associated psychosocial functioning differed little by race among obese women with BED seeking treatment in primary care settings. Clinicians should assess for and institute appropriate interventions for comorbid BED and obesity in both African American and Caucasian patients. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.     

Decreased hepatic insulin extraction in subjects with mild glucose intolerance

The fact that hyperinsulinemia occurs in simple obesity and mild glucose intolerance has been well established. Altered hepatic insulin extraction may influence the levels of circulating hormone. The simultaneous measurement of insulin and C-peptide concentrations in peripheral blood enables an in vivo estimation of hepatic insulin removal. To evaluate hepatic insulin extraction, insulin and C-peptide responses to oral glucose were studied in 176 obese and nonobese subjects with normal, impaired, or diabetic glucose tolerance. Insulin levels as well as insulin incremental areas in glucose intolerant subjects were significantly higher than in weight-matched controls. The levels of C-peptide as well as C-peptide incremental areas were only slightly enhanced in subjects with impaired glucose tolerance, whereas they were reduced in subjects with diabetic tolerance. The molar ratios of C-peptide to insulin, both in the fasting state and after ingestion of glucose, as well as the relationship between the incremental areas of the two peptides were used as measures of hepatic insulin extraction. They were significantly reduced in glucose intolerant subjects and, to a lesser extent, in nondiabetic obese subjects. These results indicate that peripheral hyperinsulinemia in subjects with simple obesity or impaired glucose tolerance is a result of both pancreatic hypersecretion and diminished hepatic insulin extraction. In subjects with a more severe degree of glucose intolerance, decreased hepatic insulin removal is the primary cause of hyperinsulinemia.     

Differences and similarities regarding adiponectin investigated in African and Caucasian women

OBJECTIVE: Concentrations of adiponectin, an adipocytokine with insulin-sensitizing actions, may vary according to ethnic group. This study aimed to determine whether fasting adiponectin levels of Caucasian and African women differ. A second objective was to determine which components of the metabolic syndrome are more closely related to adiponectinemia in both groups. DESIGN: A cross-sectional study including 102 urban African and 115 Caucasian women with a wide range of obesity aged 20-55 years. METHODS: Anthropometric measurements were taken, namely weight, height, body mass index, waist circumference, and hip circumference. Cardiovascular measurements included blood pressure and arterial compliance. Fasting blood samples were taken to determine glucose, insulin, C-peptide, leptin, adiponectin, and lipid levels. RESULTS: Mean adiponectin levels of the whole groups did not differ, but normal weight African women (N = 38) showed marginally lower adiponectin levels than their Caucasian counterparts (N = 41; P = 0.047). No differences in adiponectin were shown for overweight and obese women. Separate multiple regression analyses for ethnic groups showed that only homeostasis model assessment-insulin resistance (HOMA-IR) significantly contributed to the variance in adiponectin levels of African women, whereas leptin, triacylglycerol levels and HOMA-IR contributed significantly to adiponectin variance in Caucasian women. An additional multiple regression analysis in a combined ethnic group (N = 217) showed ethnicity to be a significant contributor to variances in adiponectin levels. CONCLUSIONS: Even though adiponectin levels of these ethnic groups are similar, different associations of adiponectin with leptin and triacylglycerol levels might indicate that there are ethnic differences regarding the mechanistic functions of adiponectin within the scope of the metabolic syndrome.     

Lifestyle intervention of hypocaloric dieting and walking reduces abdominal obesity and improves coronary heart disease risk factors in obese,postmenopausal, African-American and Caucasian women

BACKGROUND: There are few empirical data to support the claim that weight loss improves coronary heart disease (CHD) risk factors in postmenopausal women; nor is it known if there are racial differences in changes of body fat distribution, lipids, glucose tolerance, and blood pressure with weight loss. This study determined the efficacy of a lifestyle weight loss intervention in reducing total and abdominal obesity and improving CHD risk factors in obese Caucasian and African-American postmenopausal women. METHODS: Body composition (dual-energy x-ray absorptiometry), abdominal fat areas (computed tomography scan), lipoprotein lipids, insulin, glucose tolerance, and blood pressure were measured before and after 6 months of hypocaloric diet and low-intensity walking in 76 overweight or obese (body mass index > 25 kg/m(2)), Caucasian (72%) or African-American (28%), postmenopausal (age = 60 +/- 5 years) women who completed the study. RESULTS: Absolute amount of body weight lost was similar in Caucasians (-5.4 +/- 3.6 kg) and African Americans (-3.9 +/- 3.6 kg), but Caucasian women lost relatively more fat mass (p <.05). Both groups decreased their subcutaneous abdominal fat, and Caucasian women decreased their visceral fat area, but there were no racial differences in the magnitude of abdominal fat lost. The intervention decreased triglyceride and increased high-density lipoprotein and high-density lipoprotein 2 cholesterol in both races, and it decreased total and low-density lipoprotein cholesterol in Caucasian women (p <.05-.0001). Fasting glucose and glucose area during the oral glucose tolerance test decreased (p <.0001) in Caucasian women, whereas insulin area decreased in both Caucasian (p <.01) and African-American (p <.05) women. Blood pressure decreased the most in women with higher blood pressures at baseline. Changes in lipids, fasting glucose and insulin, their responses during the oral glucose tolerance test, and blood pressure were not different between racial groups. CONCLUSIONS: Weight loss achieved through a lifestyle intervention of energy restriction and increased physical activity is an equally effective therapy in African-American and Caucasian obese, postmenopausal women for improving glucose and lipid CHD risk factors.     

Comparison of body composition, adipocyte size, and glucose and insulin concentrations in Pima Indian and Caucasian children

Pima Indian adults with normal glucose tolerance have higher plasma glucose and insulin concentrations than Caucasian adults. To estimate the age of onset of these differences, and to assess their relationship to abdominal and gluteal adipocyte size, we measured adiposity, adipocyte size, and glucose and insulin concentrations during a glucose tolerance test in lean (less than 20% body fat), prepubertal children from each race. The Pima (n = 13) and Caucasian (n = 10) groups were of similar age, percent body fat, and weight. Pima Indian children had higher fasting glucose (101 +/- 2 v 94 +/- 2 mg/dL, P = .01) and insulin (22 +/- 2 v 15 +/- 2 microU/mL, P less than .01) concentrations and larger abdominal adipocytes (0.49 +/- 0.03 v 0.37 +/- 0.04 microgram lipid/cell, P less than .05) than the Caucasian children. Postprandial glucose and insulin concentrations and gluteal adipocyte size were similar in the two races. The higher plasma glucose and insulin concentrations found in Pima adults are present in lean Pima children, and are associated with increased abdominal adipocyte size. These increases may precede the development of obesity in this racial group.     

Peripheral hyperinsulinemia of simple obesity: pancreatic hypersecretion or impaired insulin metabolism?

Insulin and C-peptide levels in peripheral blood in the fasting state and after an oral glucose load were measured in 65 nondiabetic, obese subjects and 65 age- and sex-matched nondiabetic normal weight subjects. Fasting insulin and C-peptide levels were significantly higher in obese than in nonobese subjects, whereas 1 and 2 h after the oral glucose load only insulin concentrations were significantly higher in the obese subjects. C-peptide to insulin molar ratios, as well as the relation between the incremental areas of the two peptides, were used as relative measures of hepatic insulin extraction. In the fasting state the ratios between C-peptide and insulin were similar in obese and nonobese subjects, whereas after glucose they were significantly lower in the obese individuals. Similarly, the relations between C-peptide and insulin incremental areas were significantly lower in obese than in nonobese subjects. The comparison of the corresponding plasma levels and areas of C-peptide and insulin after glucose showed that for the same C-peptide value, the insulin value was higher in the obese group. Last, in obese subjects the parameter used as an estimate of hepatic removal of insulin after oral glucose inversely correlated with the fasting insulin concentration and the insulin incremental area after glucose. These results suggest that in obesity peripheral hyperinsulinemia depends on pancreatic hypersecretion of insulin in the fasting state and impaired hepatic insulin metabolism after oral glucose loading.     

Combined hyperlipidemia in relation to race/ethnicity, obesity, and insulin resistance in the Multi-Ethnic Study of Atherosclerosis

We have asked whether the prevalence of combined hyperlipidemia (CHL) differs by race/ethnicity, obesity, and insulin resistance in a contemporary, multiethnic, US cohort. We determined the prevalence and adjusted odds of CHL in a cohort of 5923 men and women free of clinically recognized cardiovascular disease and diabetes according to race/ethnicity (white, Chinese, African American, and Hispanic), obesity, and insulin resistance. Untreated lipid values were imputed for those on lipid-lowering therapy. Combined hyperlipidemia was defined using age- and sex-specific greater than or equal to 75th percentile cut points for low-density lipoprotein cholesterol and triglycerides obtained from a predominantly white North American population study. Compared with whites, adjusted odds ratios for CHL were 0.48 in African Americans (95% confidence interval [CI], 0.30-0.75), 1.33 in Hispanics (95% CI, 0.93-1.91), and 1.06 in Asians (95% CI, 0.62-1.82). Within the entire population, the adjusted odds of CHL were over 2-fold higher in overweight and obese participants compared with normal-weight participants and more than 4-fold higher in quartiles 2 through 4 of insulin resistance compared with quartile 1. African Americans had lower odds for CHL than whites despite higher body mass index and abdominal adiposity. Hispanics had a nonsignificantly higher trend, and Asians had no significantly different odds than whites. Modest increases in weight and insulin resistance were associated with significantly higher odds of CHL in a multiethnic US population. Further research is needed to determine the most efficacious diet, exercise, and drug management to decrease the risk of CHL and coronary heart disease among racial/ethnic groups in the United States.     

Insulin hypersecretion: a distinctive feature between essential and secondary hypertension.

Several studies have demonstrated that patients with hypertension have greater plasma insulin levels than normotensive subjects. The aim of the present study was to clarify if hyperinsulinemia in hypertension is a consequence of either increased pancreatic secretion or decreased hepatic clearance, and to determine whether abnormalities of glucose metabolism are equally present in essential and secondary hypertension. In an observational cross-sectional study, fasting blood glucose, plasma insulin, and plasma C-peptide levels were measured in five patient groups: 34 lean normotensive, 19 overweight normotensive, 25 lean essential hypertensive, 27 overweight essential hypertensive, and 20 secondary hypertensive subjects. The blood glucose/plasma insulin and plasma insulin/plasma C-peptide ratios were calculated as indexes of insulin sensitivity and hepatic insulin clearance, respectively. Subjects with essential hypertension and, to a greater extent, those who were overweight, exhibited significantly higher fasting insulin and C-peptide levels and significantly lower glucose/insulin ratios as compared with lean normotensive subjects. In contrast, no differences were observed between secondary hypertensive and control subjects. Mean blood pressure was significantly and independently correlated to body mass index, plasma insulin and plasma C-peptide levels, and the glucose/insulin ratio. In lean essential hypertensive and secondary hypertensive subjects, the insulin/C-peptide ratios were comparable to controls, indicating normal hepatic insulin clearance. In both overweight groups, a trend to increased insulin/C-peptide ratios was observed. This study shows that in essential hypertensive subjects, hyperinsulinemia is caused by insulin hypersecretion, whereas in overweight subjects, both increased insulin secretion and decreased hepatic insulin clearance might be involved.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ethnic differences in postprandial triglyceride response to a fatty meal and lipoprotein lipase in lean and obese African American and Caucasian women

The purpose of this study was to determine if there were differences in the expression of lipoprotein lipase (LPL) in African American (AA) and Caucasian (CA) women. LPL mRNA and protein levels were determined in subcutaneous and omental fat of lean and obese subject from the 2 races (4 groups; 12 to 15 subjects/group). LPL mRNA levels of lean AA were not different from the lean CA women in either fat depot. LPL mRNA levels in the subcutaneous fat of the obese AA were higher than those of CA women (1.3 +/- 0.1 v 0.86 +/- 0.06, P.05), but not different in omental fat. LPL mass in subcutaneous fat of lean AA was higher (0.95 +/- 0.09 v 0.64 +/- 0.06, P.05), but not different in omental fat from the CA women. LPL mass in subcutaneous and omental fat was not different in the 2 obese groups. Differences in the activity of LPL were evaluated by (1) measuring the increments of triglycerides (TG) at 2, 4, 6, and 8 hours after a fat-rich meal and (2) by measuring postheparin plasma lipolytic activity. Plasma TG levels in the lean AA were lower than those of the lean CA women at basal and at 2, 4, 6, and 8 hours postprandially. The increase in TG levels at 2 hours tended to be lower in the AA than the CA women, was significantly lower at 4 hours (24 +/- 5 v 45 +/- 7, P.05), and was not different 8 hours postprandially. No differences were observed in either the absolute or the incremental concentrations of TG in the obese groups. Postheparin plasma LPL activity was higher in the lean AA than the lean CA women (4.8 +/- 0.4 v 3.4 +/- 0.4, P.05), but not different in the obese groups. These results indicate that the lower TG concentrations in the lean AA women may be partly due to enhanced expression, activity, and intravascular availability of LPL. Furthermore, it appears that the racial differences in expression and function of LPL are attenuated with obesity.     

Leptin is independently associated with systolic blood pressure, pulse pressure and arterial compliance in hypertensive African women with increased adiposity: the POWIRS study

High leptin levels are often observed in human obesity and are implicated in obesity-related hypertension. Leptin levels have been found to be higher in hypertensive obese African-American women compared to normotensive African-American women, but a direct association between leptin and blood pressure could not be obtained. Additionally, increased adiposity has been associated with higher aortic stiffness in obese African-American women, but leptin was not included in the study. The effects of leptin on cardiovascular function in African women have not yet been determined. We hypothesised that leptin is directly associated with blood pressure and decreased arterial compliance and that leptin levels are significantly higher in hypertensive overweight/obese African women compared to normotensive overweight/obese African women. A case-case control study was performed which included 98 African women. The subjects were divided into lean normotensive (lean NT), overweight/obese normotensive (OW/OB NT) and overweight/obese hypertensive (OW/OB HT). The Finometer apparatus was used to obtain a more elaborate cardiovascular profile. Serum leptin and insulin levels as well as the HOMA-IR index were determined. Various anthropometric measures were obtained. Leptin levels were elevated (P < or = 0.05) in the OW/OB NT and HT groups compared to the lean NT group, but were similar in the OW/OB NT and HT groups. After adjusting for obesity, insulin resistance, hyperinsulinaemia and age, a direct positive correlation was obtained between leptin and systolic blood pressure (SBP) (P < or = 0.05; r = 0.68) in the OW/OB HT group. Additionally, leptin also correlated negatively with arterial compliance (P< or = 0.05; r = -0.76) and positively with pulse pressure (P < or = 0.05; r = 0.71) in the OW/OB HT group. In conclusion, even though leptin levels were the same in OW/OB HT and NT African women, leptin was directly and positively associated with SBP and pulse pressure and negatively with C(W) only in OW/OB HT African women, independent of obesity, insulin-resistance, hyperinsulinaemia and age.     

Reduced hepatic insulin extraction in obesity: relationship with plasma insulin levels

To elucidate if there are alterations in insulin metabolic clearance in obesity under basal conditions, plasma insulin and C-peptide were measured in 22 obese patients and 8 normal subjects, and the plasma C-peptide to insulin molar ratio was used as an index of hepatic insulin extraction. In obese patients, the C-peptide to insulin molar ratio correlated indirectly with basal plasma insulin levels (r = 0.71; P less than 0.001), being low in the obese patients with higher insulin levels and within the normal range in obese patients in which insulin levels were similar to those of control subjects. It is suggested that hepatic insulin extraction is decreased in obesity, even under basal conditions, but this alteration is only manifested when plasma insulin levels are high.     

C-Peptide and insulin secretion in Pima Indians and Caucasians: constant fractional hepatic extraction over a wide range of insulin concentrations and in obesity.

Peripheral serum insulin and C-peptide concentrations during oral glucose tolerance tests were measured in 10 nondiabetic Pima Indians and 10 nondiabetic Caucasians with varying degrees of obesity. Although both insulin and C-peptide levels were elevated in the Indians compared to the Caucasians (p less than 0.05), hepatic insulin extraction, measured by comparing the C-peptide to insulin ratios, was similar over a wide range of insulin concentrations in both groups. The ratios of C-peptide to insulin were independent of the degree of obesity. These studies indicate that the peripheral hyperinsulinemia in Pima Indians and obese subjects is due in general to pancreatic hypersecretion rather than to diminished hepatic extraction of insulin.     

伴腹型肥胖的2型糖尿病患者的临床特点分析

目的:探讨伴腹型肥胖的2型糖尿病(T2DM)患者的临床特点。方法:选取T2DM住院患者171例,按腰围分为腹型肥胖组(AO组,男性>90 cm,女性>85 cm)和非腹型肥胖组(NAO组,男性≤90 cm,女≤85 cm),比较各组的糖代谢、脂代谢、新稳态模型(HOMA2)胰岛B细胞分泌指数(HOMA2-B)和胰岛素敏感性指数(HOMA2-S)。结果:AO组血压、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、C反应蛋白(CRP)、血糖和C肽(CP0、CP30、CP120)均较NAO组显著升高,而高密度脂蛋白胆固醇(HDL-C)、HOMA2-S则明显降低。结论:伴腹型肥胖的T2DM患者多伴TG水平升高,且血糖失控和胰岛素抵抗程度更重。     

Inflammation, obesity and cardiovascular function in African and Caucasian women from South Africa: the POWIRS study

The integrated relationship between inflammation, obesity and cardiovascular disease is currently a subject of much research interest. These specific relationships, however, have not been studied in-depth in South African population groups in order to determine the role of ethnicity. It is known that Africans, compared to Caucasians, suffer from a high prevalence of hypertension. It was therefore hypothesized that the levels of inflammatory markers (high-sensitivity C-reactive protein (hsCRP), fibrinogen and leptin) are higher in Africans compared to Caucasians and are notably associated with cardiovascular dysfunction in Africans. Apparently healthy African (N=102) and Caucasian (N=115) women, matched for age and body mass index (BMI), were recruited. Leptin, hsCRP, fibrinogen and lipid levels, waist circumference (WC), BMI, systolic and diastolic blood pressure, cardiac output (CO), total peripheral resistance (TPR) and Windkessel compliance were measured. Results showed that the levels of leptin, hsCRP and fibrinogen were significantly higher (P<0.05) in the African women. The inflammatory markers correlated strongly with cardiovascular parameters, age and obesity (BMI, WC) in both groups, but after adjusting for age and obesity, none of the correlations were significant anymore. Multiple regression analyses (with leptin, hsCRP or fibrinogen as dependent variable) showed that only leptin levels of African women were explained by cardiovascular parameters (BP, TPR and CO). In conclusion, even though African women had significantly higher leptin, hsCRP, fibrinogen and blood pressure levels than Caucasian women, no cardiovascular parameters explained the variation in the inflammatory markers (except for leptin levels of African women).     

Effects of a westernized lifestyle on the association between fasting serum nonesterified fatty acids and insulin secretion in Japanese men

The effects of the prolonged elevation of nonesterified fatty acid (NEFA) levels on insulin secretion have been controversial and thought to be sex-specific. To investigate the association between a westernized lifestyle and the effects of NEFA on insulin secretion in Japanese men, we examined 67 nondiabetic Japanese-American men and 220 nondiabetic native Japanese men who underwent a 75-g oral glucose tolerance test (OGTT). Most Japanese Americans we surveyed are genetically identical to Japanese living in Japan, but their lifestyle is more westernized. Sets of multiple regression analyses were performed to evaluate the relationship between the sum of the immunoreactive insulin (IRI) levels during the OGTT ((Sigma)IRI) and clinical parameters. Japanese Americans had higher levels of fasting IRI, (Sigma)IRI, and a higher insulin resistance index (homeostasis model assessment for insulin resistance [HOMA-IR]) than native Japanese, whereas there were no significant differences in fasting NEFA and triglyceride levels. A multiple regression analysis adjusted for age, fasting triglycerides, and body mass index (BMI) demonstrated that the fasting NEFA level was an independent determinant of the (Sigma)IRI only in Japanese-American men ( P = .001), but not in native Japanese men ( P = .054). Even when HOMA-IR was included in models instead of BMI, the NEFA level was a significant variable of (Sigma)IRI only in Japanese Americans ( P < .001), and not in native Japanese ( P = .098). In addition, a multiple regression analysis adjusted for age, fasting triglycerides, and BMI demonstrated that the fasting NEFA level was the only independent determinant of (Sigma)C-peptide in Japanese-American men ( P = .041). In conclusion, NEFA seems to be associated with insulin secretion independent of obesity or HOMA-IR. A westernized lifestyle may increase the effects of serum fasting NEFA levels on total insulin secretion after a glucose load in Japanese men.     

Fenofibrate lowers adiposity and corrects metabolic abnormalities, but only partially restores endothelial function in dietary obese rats

In humans, dietary-induced obesity markedly increases plasma lipid profile and impairs vascular function leading to increased incidence of cardiovascular events. We have recently reported that chronic withdrawal of obesity-inducing diet attenuates obesity and completely corrects endothelial function. The aim of this study was to investigate whether fenofibrate-induced decrease in adiposity would also correct vascular function in the presence of obesity-inducing diet. Wistar rats were fed with either standard laboratory chow (lean, n = 9) or given a highly palatable diet (diet-fed, n = 18) for 15 weeks. After 7 weeks, half of the diet-fed group was treated with fenofibrate (fenofibrate-treated, n = 9) for 8 weeks before being sacrificed. Untreated diet-fed (n = 9) rats had significantly higher body weight, total fat mass (by up to two-fold, p < 0.001 for both), and raised fasting plasma levels of insulin, leptin and triglycerides (up to 110%; p < 0.001), but not glucose or nonesterified fatty acids (NEFA) than both lean control and fenofibrate-treated groups. Resistance mesenteric arteries responses to KCl- and noradrenaline-induced vasoconstriction were similar in all three groups. However, compared with lean controls, endothelium-dependent vasorelaxation responses were shifted to the right in both untreated and fenofibrate-treated diet-fed groups. Fenofibrate treatment improved endothelium-dependent vasorelaxation at only high carbamycholine concentrations (10 microM). There were no differences in endothelium-independent vasorelaxation between the three groups. These results indicate that, in the presence of obesity-inducing diet, fenofibrate markedly reverses obesity and corrects insulin resistance and lipid profile, but it only has a limited beneficial effect on vascular function. Therefore, it seems that diet component rather than obesity per se plays a key role in the genesis of vascular abnormalities.     

Lack of effect of a physiological elevation of plasma non-esterified fatty acid levels on insulin secretion

Elevated plasma non-esterified fatty acid (NEFA) levels in obese subjects may contribute to their higher insulin secretory rates by direct effects on the islet B-cells. This may involve short-term metabolic effects, or long-term effects on islet B-cell mass, which is characteristically increased in obesity. We examined the effects of elevating plasma NEFA levels for 5.5 to 7 h on insulin secretion after an overnight fast and during a 90 min 12 mmol/l hyperglycemic clamp in 9 normal women (40.1 +/- 9.5 years [mean +/- SD]; BMI: 25.2 +/- 3.72 kg/m(2) ). Subjects were studied twice. In one study plasma NEFA levels were increased approximately 2-fold by infusion of 20% Intralipid (60 ml/h) and heparin (900 U/h) for 5.5 h before and throughout the glucose clamp. Elevated NEFA levels were associated with a small increase in fasting plasma glucose (5.0 +/- 0.1 vs 4.7 +/- 0.1 mmol/l, P <0.05) and C-peptide levels (0.54 +/- 0.09 vs 0.41 +/- 0.06 nmol/l, P <0.05). The increase in fasting insulin levels did not, however, reach statistical significance (9.0 +/- 2.5 vs 5.3 +/- 1.4 mU/l, NS). During the glucose clamp, plasma NEFA levels were suppressed to very low levels in the saline control study. Although plasma NEFA levels also fell in the lipid/heparin study, they remained significantly higher than on the control day, and somewhat higher than might be expected postprandially in obese subjects. During the glucose clamps, plasma glucose, insulin, and C-peptide profiles were similar on the two study days. No difference in either first or second phase insulin secretion was observed between the two studies. In conclusion, our findings do not support the idea that the exaggerated insulin secretion in obesity is mediated by short-term effects of plasma NEFA levels on islet B-cell metabolism, independent of plasma glucose levels.