Circulating fatty acids, non-high density lipoprotein cholesterol, and insulin-infused fat oxidation acutely influence whole body insulin sensitivity in nondiabetic men

Circulating lipids and tissue lipid depots predict insulin sensitivity. Associations between fat oxidation and insulin sensitivity are variable. We examined whether circulating lipids and fat oxidation independently influence insulin sensitivity. We also examined interrelationships among circulating lipids, fat oxidation, and tissue lipid depots. Fifty-nine nondiabetic males (age, 45.4 +/- 2 yr; body mass index, 29.1 +/- 0.5 kg/m(2)) had fasting circulating nonesterified fatty acids (NEFAs) and lipids measured, euglycemic-hyperinsulinemic clamp for whole body insulin sensitivity [glucose infusion rate (GIR)], substrate oxidation, body composition (determined by dual energy x-ray absorptiometry), and skeletal muscle triglyceride (SMT) measurements. GIR inversely correlated with fasting NEFAs (r = -0.47; P = 0.0002), insulin-infused NEFAs (n = 38; r = -0.62; P < 0.0001), low-density lipoprotein cholesterol (r = -0.50; P < 0.0001), non-high-density lipoprotein cholesterol (r = -0.52; P < 0.0001), basal fat oxidation (r = -0.32; P = 0.03), insulin-infused fat oxidation (r = -0.40; P = 0.02), SMT (r = -0.28; P < 0.05), and central fat (percentage; r = -0.59; P < 0.0001). NEFA levels correlated with central fat, but not with total body fat or SMT. Multiple regression analysis showed non-high-density lipoprotein cholesterol, fasting NEFAs, insulin-infused fat oxidation, and central fat to independently predict GIR, accounting for approximately 60% of the variance. Circulating fatty acids, although closely correlated with central fat, independently predict insulin sensitivity. Insulin-infused fat oxidation independently predicts insulin sensitivity across a wide range of adiposity. Therefore, lipolytic regulation as well as amount of central fat are important in modulating insulin sensitivity.     

Metabolic cardiovascular syndrome in obese prepubertal children: the role of high fasting insulin levels

The aim of this study was to detect the presence and degree of impairment of cardiovascular disease (CVD) risk factors, grouped as metabolic cardiovascular syndrome (MCS), in obese prepubertal children. We also assessed the influence of high fasting insulin levels in this pathological status. A cross-sectional study was performed on obese children based on fasting blood samples. Subjects were 61 obese children (aged 6 to 9 years) and an equal number of non-obese children paired by age and sex. The obese children presented the following characteristics in comparison to the non-obese group: significantly high levels of insulin (8.2 +/- 0.52 v 6.12 +/- 0.34 microU/mL), triglycerides (TG) (0.79 +/- 0.04 v 0.60 +/- 0.02 mmol/L), uric acid (0.24 +/- 0.005 v 0.21 +/- 0.004 mmol/L), systolic (SBP) (94.59 +/- 1.06 v 88.85 +/- 1.2 mm Hg) and diastolic (56.49 +/- 1.07 v 52.21 +/- 1.06 mm Hg) blood pressure (DBP), and low levels of high-density lipoprotein cholesterol (HDL-C) (1.30 +/- 0.04 v 1.46 +/- 0.03 mmol/L), and nonesterified fatty acids (0.407 +/- 0.02 v 0.505 +/- 0.02 mmol/L). The hyperinsulinemic obese children showed the same types of differences when compared with the normoinsulinemic group. In the obese group, having adjusted for age, waist/hip ratio (WHR), body mass index (BMI), and sex hormone-binding globulin (SHBG), insulin was an independent prediction factor for triglycerides (P =.0004), apolipoprotein A-I (Apo-AI) (P =.005), and alanine aminotransferase (ALT) (P =.029). BMI was an independent prediction factor for HDL-C (P =.001) and triglycerides (P =.027). However, insulin was an independent prediction factor in the control group for triglycerides (P =.0002) and SBP (P =.012), just as BMI was for HDL-C (P =.011) and uric acid (P =.041). We conclude that the cluster of CVD risk factors associated with MCS and intra-abdominal fat is present in obese prepubertal children. This situation seems to depend, to a large extent, on the insulin basal level. The apparent association between BMI and MCS is due to the correlation between BMI and insulin, and to the fact that insulin associates with MCS. Within the obese group, hyperinsulinemic children present the greatest impairment in the parameters considered to be constituents of MCS.     

Study of the effect of changing glucose, insulin, and insulin-like growth factor-I levels on serum corticosteroid binding globulin in lean, obese, and obese subjects with glucose intolerance

We have previously described that serum corticosteroid binding globulin (CBG) concentrations are associated with insulin secretion. The present study was designed to evaluate the effects of changing insulin concentrations, both endogenous and after exogenous insulin administration, on circulating CBG levels in vivo. Serum CBG concentrations were measured during an insulin-modified frequently sampled intravenous (IV) glucose tolerance test (FSIVGT) in 14 lean and 19 obese otherwise healthy subjects with varying degrees of glucose tolerance. Acute insulin response to glucose (AIRg) correlated significantly with serum CBG concentrations at time 0 (r = -.38, P =.029), 22 minutes (r = -.41, P =.01), 50 minutes (r = -.41, P =.01), and 180 minutes (r = -.39, P =.02). Insulin sensitivity (S(I)) was not associated with serum CBG concentration at time 0 (r = -.16, P = not significant [NS]), but correlated significantly with CBG concentration at 22 minutes (r = -.41, P =.02) and 50 minutes (r = -.35, P =.048) of the FSIVGT. In lean subjects, serum CBG concentration decreased significantly after IV insulin from 37.9 +/- 5.4 to 35.4 +/- 3 mg/L (P =.02) and returned to basal levels thereafter. In contrast, obese, glucose-tolerant subjects had lower CBG levels than lean and obese glucose intolerant subjects (33.8 +/- 3.0 v 37.9 +/- 5.4 and 39.8 +/- 4.4 mg/L, respectively), and their serum CBG concentrations remained unchanged during FSIVGT. Mean serum-free insulin-like growth factor-I (IGF-I) concentrations steadily declined from 1.21 +/- 0.81 to 0.8 +/- 0.36 microg/L during the FSIVGT, and this effect was restricted to lean subjects. Basal serum-free IGF-I did not correlate with CBG levels at time 0, but correlated inversely with the serum CBG concentrations at 22 minutes (r = -.36, P =.04). Stepwise multivariant analysis showed that AIRg (P =.035) and S(I) (P =.046), but not free IGF-I levels, independently contributed to 28% of CBG variance at 22 minutes. These results suggest that insulin, but not IGF-I, constitutes an important negative regulator of CBG liver synthesis. Endogenous and exogenous insulin do not affect serum CBG concentrations in insulin-resistant obese subjects with preserved or decreased insulin secretion. Obese glucose-tolerant subjects are hypothesized to exhibit tonically inhibited serum CBG levels. In contrast, in lean subjects, the higher the insulin secretion the lower the serum CBG concentration. The mechanisms of this CBG inhibitory effect exerted by insulin and its implication on cortisol homeostasis and fat distribution in humans await further investigations.     

Relationships of body fat distribution,insulin sensitivity and cardiovascular risk factors in lean,healthy non-diabetic Thai men and women

In order to study the relationships of body fat distribution, insulin sensitivity and cardiovascular risk factors in lean, healthy non-diabetic Thai men and women, 32 healthy, non-diabetic subjects, 16 men and 16 women, with respective mean age 28.4+/-6.6 (S.D.) and 32.8+/-8.9 years, mean BMI 21.0+/-2.8 and 21.2+/-3.7 kg/m(2), were measured for total body fat and abdominal fat by dual energy X-ray absorptiometry (DEXA), anthropometry and insulin sensitivity by euglycemic hyperinsulinemic clamp. Cardiovascular risk factors included fasting and post-glucose challenge plasma glucose and insulin, blood pressure, lipid profile, fibrinogen and uric acid. For similar age and BMI, men had a lower amount and percent of total body fat, but had a higher proportion of abdominal/total body fat than women. In men, insulin sensitivity, as determined by glucose infusion rate during euglycemic hyperinsulinemic clamp, was inversely correlated with total body fat, abdominal fat, BMI and waist circumference, whereas only total body fat, but not abdominal fat, BW and hip circumference were inversely correlated with insulin sensitivity in women. No cardiovascular risk factors, except area under the curve (AUC), of plasma insulin in women correlated with insulin sensitivity when adjusted for total body fat. After age adjustment, total body fat was better correlated with fasting and AUC of plasma glucose and insulin in men and with systolic blood pressure as well as triglyceride levels in women. Only HDL-C in men was better correlated with abdominal fat. In conclusion, there were sex-differences in body fat distribution and its relationship with insulin sensitivity and cardiovascular risk factors in lean, healthy non-diabetic Thai subjects. Total body fat was a major determinant of insulin sensitivity in both men and women, abdominal fat may play a role in men only. Body fat, not insulin sensitivity, was associated with cardiovascular risk factors in these lean subjects.     

Predictors of adipose tissue lipoprotein lipase in middle-aged and older men: relationship to leptin and obesity, but not cardiovascular fitness

The effects of long-term endurance exercise training, body composition, and cardiovascular fitness (VO2max) on the activity of adipose tissue lipoprotein lipase (AT-LPL) and lipoprotein lipids were examined in 66 healthy age-matched middle-aged and older men (mean +/- SE, 61 +/- 1 years). We compared subcutaneous abdominal (ABD) and gluteal (GLT) heparin-elutable AT-LPL activity in 19 master athletes (VO2max > 40 mL/kg/min) and 20 lean sedentary men (VO2max < 40 mL/kg/min) versus 27 obese sedentary men (VO2max < 40 mL/kg/min; body fat > 27%). Fasting insulin and leptin levels were similar in master athletes and lean sedentary men, but were lower than in obese sedentary men. There were no differences in fasting values for total cholesterol or low-density lipoprotein cholesterol (LDL-C) among the groups, but master athletes had lower triglyceride (TG) values (P < .05) and higher high-density lipoprotein cholesterol (HDL-C) and HDL2-C (P < .05) than obese and lean sedentary men. There were no regional (ABD v GLT) differences in the activity of AT-LPL in these groups, but obese sedentary men had higher levels of ABD AT-LPL (2.1 +/- 0.3 nmol/10(6) cells x min) than lean sedentary men (0.8 +/- 0.2) and master athletes (0.5 +/- 0.1, P = .01). Similar results were observed for GLT AT-LPL. Both ABD and GLT AT-LPL activity correlated positively with percent body fat (r = .46 to .54, P < .001), fasting insulin (r = .37 to .45, P < .001), and leptin (r = .61 to .65, P < .0001), but not with VO2max. In stepwise multiple regression analysis, leptin was the main independent predictor of ABD (R2 = .43, P < .0001) and GLT (R2 = .40, P < .0001) AT-LPL activity. Plasma TG correlated positively (r = .32, P < .01) and HDL-C correlated negatively (r = -.32, P = .02) with ABD AT-LPL activity, but these relationships were not significant after controlling for percent body fat or leptin. The results of this study indicate that in healthy middle-aged and older men, the major determinants of AT-LPL activity are obesity and its major associated hormones, leptin and insulin, not cardiovascular fitness, and also suggest that the higher HDL-C levels observed in endurance-trained men are not associated with increased AT-LPL activity.     

Nicotinic acid-induced insulin resistance is related to increased circulating fatty acids and fat oxidation but not muscle lipid content

Insulin resistance is associated with increased circulating lipids and skeletal muscle lipid content. Chronic nicotinic acid (NA) treatment reduces insulin sensitivity and provides a model of insulin resistance. We hypothesized that the reduction in insulin sensitivity occurs via elevation of circulating nonesterified fatty acids (NEFAs) and an increase in intramyocellular lipid (IMCL). A total of 15 nondiabetic males (mean age 27.4 +/- 1.6 years) were treated with NA (500 mg daily for 1 week, 1 g daily for 1 week). Insulin sensitivity (glucose infusion rate [GIR]) was determined pre- and post-NA by euglycemic-hyperinsulinemic clamp. Substrate oxidation was determined by indirect calorimetry. Skeletal muscle lipid was assessed by estimation of long-chain acyl-CoA (LCACoA) and triglyceride (TG) content and by (1)H-magnetic resonance spectroscopy quantification of IMCL (n = 11). NA reduced GIR (P =.03) and nonoxidative glucose disposal (P <.01) and increased fasting NEFAs (P =.01). The decrease in GIR related significantly to the increase in fasting NEFAs (r(2) =.30, P =.03). The intrasubject increase in basal and clamp fat oxidation correlated with the decrease in GIR (r(2) =.45, P <.01 and r(2) =.63, P <.01). There were no significant changes in muscle LCACoA, TG, or IMCL content. Therefore, induction of insulin resistance by NA occurs with increased availability of circulating fatty acids to muscle rather than with increased muscle lipid content.     

Abdominal fat index by ultrasound does not estimate the metabolic risk factors of cardiovascular disease better than waist circumference in severe obesity

OBJECTIVE: To evaluate by ultrasound the ratio between preperitoneal (P) and subcutaneous (S) fat (AFI), in quantifying the cardiovascular risk in 258 obese patients (BMI 41.2+/-6.3 kg/m2; age 45.1 +/- 13.6 years). RESEARCH METHODS AND PROCEDURES: Glucose, insulin, lipid profile, uric acid and fibrinogen were measured. HOMA-IR, waist girth, AFI and quartiles of BMI were calculated. RESULTS: AFI lowered with increasing BMI and showed a positive correlation with TGL (r=0.37, P<0.01) and uric acid (r=0.40, P<0.001) in the 1st quartile of BMI (30.2-36.4) and a negative correlation with HDL (r=- 0.32, P<0.001) in the 3rd quartile (40.6-45.1). When BMI exceeded the value of 45.2 kg/m2 these correlations were no longer significant. In all subjects S correlated positively with uric acid (r=0.64, P<0.001), and negatively with HOMA-IR (r=- 0.41, P<0.001) and TGL (r=- 0.35, P=0.02); P correlated positively with CHOL (r=0.48, P=0.04) and TGL (r=0.33, P=0.03), and negatively with HDL (r=- 0.46, P=0.03). Waist girth showed more significant correlations than AFI in the lower quartiles of BMI, but not at the highest one. DISCUSSION: AFI, P and S, as waist girth do not seem to quantify the metabolic risk factors of cardiovascular disease in severe obese subjects, but AFI is probably useful in obese populations with BMI<45 kg/m2, even though not as strong as waist girth.     

Elevated matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in obese children and adolescents

Matrix metalloproteinases (MMPs) have been implicated in the atherosclerotic process and risk factors for the disease such as hypertension, hyperlipidemia, or diabetes mellitus in adults. So far, circulating levels of MMPs and their tissue inhibitors (TIMPs) have not been assessed in children and adolescents with obesity, a known risk factor for cardiovascular disease. Plasma levels of MMP-9 and TIMP-1 were measured immunoenzymatically in 45 obese children and adolescents, aged 15 +/- 1.8 years. The control group consisted of 28 healthy children, aged 14.5 +/- 2.5 years. MMP-9 and TIMP-1 concentrations were higher in obese children than in the control group (MMP-9: 553.5 +/- 311 vs 400.4 +/- 204 ng/mL, respectively; P = .02; TIMP-1: 161.2 +/- 32 vs 143.1 +/- 20.1 ng/mL, respectively; P = .03). We found significantly higher levels of MMP-9 in obese children with coexisting hypertension than in obese normotensive patients (635 +/- 308 vs 450 +/- 289 ng/mL, respectively; P = .04). MMP-9 correlated with body mass index (BMI) (r = 0.33, P = .005) and fasting insulin (r = 0.3, P = .013); TIMP-1 correlated with BMI (r = 0.35, P = .006). In the group of obese hypertensive children (n = 25), MMP-9 correlated with BMI (r = 0.41, P = .001), systolic blood pressure (r = 0.41, P = .002), fasting insulin (r = 0.37, P = .006), and homeostasis model assessment index of insulin resistance (r = 0.27, P = .03). TIMP-1 correlated with BMI (r = 0.33, P = .025) and systolic (r = 0.38, P = .008) and diastolic (r = 0.47, P = .001) blood pressure. In the regression models, MMP-9 was found to be dependent on fasting insulin (R(2) = 0.16, P = .04), and TIMP-1 on BMI (R(2) = 0.14, P = .04). In the obese hypertensive group, TIMP-1 was dependent on diastolic blood pressure (R(2) = 0.18, P = .04). Obese children and adolescents have elevated plasma concentrations of MMP-9 and TIMP-1. Coexistence of hypertension may exacerbate alterations of extracellular matrix turnover in these patients. It might be hypothesized that elevated MMP and TIMP concentrations may be related to increased cardiovascular risk in obese and particularly in obese hypertensive children and adolescents.     

Raising lipids acutely reduces baroreflex sensitivity

Impaired baroreflex sensitivity (BRS) is associated with hypertension and cardiovascular risk. Lipid abnormalities accompanying insulin resistance may impair BRS. To test this, nine obese, dyslipidemic hypertensive and seven healthy normotensive individuals were studied. The BRS was measured during a phenylephrine infusion before and after nonesterified fatty acids (NEFAs) and triglycerides were raised for 1 h with an Intralipid and heparin infusion, ie, acute dyslipidemia. The obese group had higher values than lean controls for several components of the insulin resistance syndrome including blood pressure (BP) and heart rate, as well as fasting insulin, triglycerides, and NEFA. The BRS was lower in obese hypertensive subjects than healthy controls at baseline (P < .0001); BRS declined from 8.3 +/- 0.4 to 5.2 +/- 0.3 (P < .001) in obese hypertensive subjects and from 15.9 +/- 2.2 to 7.5 +/- 0.7 msec/mm Hg (P = .04) in controls with acute dyslipidemia. The reduction in BRS correlated with the rise in NEFAs (r = -0.59, P = .02) but not triglycerides (r = -0.07, P = NS). These observations indicate that elevating NEFAs acutely impairs BRS. The findings suggest that lipid abnormalities in obese hypertensives may contribute to elevated BP and increased cardiovascular events by impairing BRS.     

Elevated plasma levels of alpha-melanocyte stimulating hormone (alpha-MSH) are correlated with insulin resistance in obese men

OBJECTIVE: The role of alpha-melanocyte stimulating hormone (MSH) in obesity has been well-documented. However, circulating alpha-MSH concentrations in obese men and their relationship with clinical indicators of obesity and glucose metabolism have not as yet been evaluated. METHODS: We measured the plasma concentrations of alpha-MSH in 15 obese and 15 non-obese male subjects. The relationship of the plasma concentrations of alpha-MSH with body mass index (BMI), body fat mass (measured by bioelectric impedance), body fat distribution (measured by computed tomography), insulin levels, insulin resistance (assessed by the glucose infusion rate (GIR) during an euglycemic hyperinsulinemic clamp study) and with the serum concentrations of leptin and TNF-alpha were also evaluated. RESULTS: In obese men, the plasma alpha-MSH concentrations were significantly increased compared with those in non-obese men (P< 0.02). The plasma levels of alpha-MSH were positively correlated with BMI (r= 0.560, P< 0.05), fasting insulin levels (r=0.528, P< 0.05) and with visceral fat area (r=0.716, P<0.01), but negatively correlated with GIR (r= -0.625, P< 0.02) in obese male subjects. There were significant correlations between plasma concentrations of alpha-MSH and visceral fat area (r=0.631, P< 0.02), and GIR (r = -0.549, P< 0.05) in non-obese male subjects. Circulating concentrations of alpha-MSH were not significantly correlated with the serum concentrations of leptin and TNF-alpha in both obese and non-obese men. CONCLUSION: Circulating concentrations of alpha-MSH are significantly increased and correlated with insulin resistance in obese men.     

In vitro evidence that hyperglycemia stimulates tumor necrosis factor-alpha release in obese women with polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) are often insulin resistant and have chronic low-level inflammation. The purpose of this study was to determine the effects of hyperglycemia in vitro on tumor necrosis factor (TNF)-alpha release from mononuclear cells (MNC) in PCOS. Twelve reproductive-age women with PCOS (six lean, six obese) and 12 age-matched controls (six lean, six obese) were studied. Insulin sensitivity (IS(HOMA)) was estimated from fasting levels of glucose and insulin and percent truncal fat was determined by dual energy absorptiometry (DEXA). TNFalpha release was measured from MNC cultured under euglycemic and hyperglycemic conditions. IS(HOMA) was higher in obese women with PCOS than in lean women with PCOS (student's t-test; 73.7 +/- 14.8 vs 43.1 +/- 8.6, P < 0.05), but similar to that of obese controls. IS(HOMA) was positively correlated with percent truncal fat (r=0.57, P < 0.04). Obese women with PCOS exhibited an increase in the percent change in TNFalpha release from MNC in response to hyperglycemia compared with obese controls (10 mM, 649 +/- 208% vs 133 +/- 30%, P < 0.003; 15 mM, 799 +/- 347% vs 183 +/- 59%, P < 0.04). The TNFalpha response directly correlated with percent truncal fat (r=0.45, P < 0.03) and IS(HOMA) (r=0.40, P < 0.05) for the combined groups, and with plasma testosterone (r=0.60, P < 0.05) for women with PCOS. MNC of obese women with PCOS exhibit an increased TNFalpha response to in vitro physiologic hyperglycemia. MNC-derived TNFalpha release may contribute to insulin resistance and hyperandrogenism, particularly when the combination of PCOS and increased adiposity is present.     

Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects

BACKGROUND AND AIMS: Abdominal fat accumulation (visceral/hepatic) has been associated with hepatic insulin resistance (IR) in obesity and type 2 diabetes (T2DM). We examined the relationship between visceral/hepatic fat accumulation and hepatic IR/accelerated gluconeogenesis (GNG). METHODS: In 14 normal glucose tolerant (NGT) (body mass index [BMI] = 25 +/- 1 kg/m(2)) and 43 T2DM (24 nonobese, BMI = 26 +/- 1; 19 obese, BMI = 32 +/- 1 kg/m(2)) subjects, we measured endogenous (hepatic) glucose production (3-(3)H-glucose) and GNG ((2)H(2)O) in the basal state and during 240 pmol/m(2)/min euglycemic-hyperinsulinemic clamp, and liver (LF) subcutaneous (SAT)/visceral (VAT) fat content by magnetic resonance spectroscopy/magnetic resonance imaging. RESULTS: LF was increased in lean T2DM compared with lean NGT (18% +/- 3% vs 9% +/- 2%, P < .03), but was similar in lean T2DM and obese T2DM (18% +/- 3% vs 22% +/- 3%; P = NS). Both VAT and SAT increased progressively from lean NGT to lean T2DM to obese T2DM. T2DM had increased basal endogenous glucose production (EGP) (NGT, 15.1 +/- 0.5; lean T2DM, 16.3 +/- 0.4; obese T2DM, 17.2 +/- 0.6 micromol/min/kg(ffm); P = .02) and basal GNG flux (NGT, 8.6 +/- 0.4; lean T2DM, 9.6 +/- 0.4; obese T2DM, 11.1 +/- 0.6 micromol/min/kg(ffm); P = .02). Basal hepatic IR index (EGP x fasting plasma insulin) was increased in T2DM (NGT, 816 +/- 54; lean T2DM, 1252 +/- 164; obese T2DM, 1810 +/- 210; P = .007). In T2DM, after accounting for age, sex, and BMI, both LF and VAT, but not SAT, were correlated significantly (P < .05) with basal hepatic IR and residual EGP during insulin clamp. Basal percentage of GNG and GNG flux were correlated positively with VAT (P < .05), but not with LF. LF, but not VAT, was correlated with fasting insulin, insulin-stimulated glucose disposal, and impaired FFA suppression by insulin (all P < .05). CONCLUSIONS: Abdominal adiposity significantly affects both lipid (FFA) and glucose metabolism. Excess VAT primarily increases GNG flux. Both VAT and LF are associated with hepatic IR.     

Fasting and daylong triglycerides in obesity with and without type 2 diabetes

Postprandial hypertriglyceridemia associated with insulin resistance is one of the cardiovascular risk factors in obesity and type 2 diabetes. It is not known whether diabetics have a more pronounced postprandial hypertriglyceridemia than obese subjects. Daylong triglyceridemia, representing postprandial lipemia, was determined in obese subjects with and without type 2 diabetes and in lean subjects. Nineteen type 2 diabetics (F/M: 7/12, body mass index [BMI]: 30.6 +/- 5.4 kg/m(2)), 45 obese nondiabetics (F/M: 16/29, BMI: 29.5 +/- 2.6 kg/m(2)) and 78 lean subjects (F/M: 28/50, BMI: 23.7 +/- 2.2 kg/m(2)) measured capillary triglycerides (TGc) during 3 days on 6 fixed time-points each day in an out-of-hospital situation. Daylong TGc profiles were calculated as mean integrated area under the TGc-curve (TGc-AUC). Fasting plasma TG were higher in diabetics and obese nondiabetics (1.81 +/- 0.79 and 1.77 +/- 0.80 mmol/L) compared with lean subjects (1.23 +/- 0.67 mmol/L, P <.001). TGc-AUC was similarly increased in both diabetics and obese nondiabetics (35.0 +/- 12.1 and 35.2 +/- 10.6 mmol.1 h/L) compared with lean controls (25.5 +/- 12.0 mmol.1 h/L, P <.001). Self-reported energy intake was not significantly different between the groups. Fasting TGc (r =.87, P <.001) and waist circumference (r =.51, P <.001) were the parameters best associated with TGc-AUC. Using stepwise multiple regression analysis, fasting TGc, BMI, total cholesterol, and high-density lipoprotein (HDL) cholesterol were the best predictors of TGc-AUC, explaining 77% of the variation. The cut-off level for "normal" TGc-AUC, calculated as the 75th percentile of TGc-AUC in lean subjects, was 30.7 mmol.1 h/L and corresponded with a fasting TGc of 1.8 mmol/L (eg, 1.6 mmol/L in plasma), calculated using univariate regression analysis. In conclusion, daylong triglyceridemia is similarly increased in diabetics and obese nondiabetics compared with lean subjects. Fasting TG and central obesity largely determine daylong triglyceridemia, independent of the presence of type 2 diabetes. Decreasing fasting plasma TG below 1.6 mmol/L could lead to a normalization of postprandial lipemia in obese subjects with and without diabetes.     

Association between hypoadiponectinemia and cardiovascular risk factors in nonobese healthy adults

Adiponectin levels are significantly lower in obese adult patients with type 2 diabetes mellitus, essential hypertension, dyslipidemia, and cardiovascular disease. However, the role of hypoadiponectinemia in nonobese healthy adults has not been fully elucidated. In this study, we examined the association between hypoadiponectinemia and cardiovascular risk factors and estimated plasma adiponectin values in nonobese, apparently healthy adults. A total of 204 male and 214 female healthy individuals aged 20 to 80 years, with a body mass index (BMI) of less than 25 kg/m2, were included in this study. We measured patients' plasma adiponectin levels, serum lipid profiles, high-sensitivity C-reactive protein (hs-CRP) levels, fasting glucose levels, and fasting insulin levels. Mean values of plasma adiponectin were 5.45 +/- 3.3 microg/mL in male and 8.16 +/- 4.6 microg/mL in female subjects. The hypoadiponectinemia group (< 4.0 microg/mL) had significantly higher levels (P < .01) of BMI, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglycerides, but lower levels of high-density lipoprotein cholesterol (HDL-C). In males, plasma adiponectin levels were inversely correlated with BMI (r = -0.32, P < .01), HOMA-IR (r = -0.14, P < .05), triglyceride levels (r = -0.17, P < .05), and hs-CRP levels (r = -0.15, P < .05), and positively correlated with HDL-C (r = 0.24, P < .01). In females, plasma adiponectin levels were negatively correlated with BMI (r = -0.31, P < .01), fasting glucose (r = -0.18, P < .01), fasting insulin (r = -0.23, P < .01), HOMA-IR (r = -0.24, P < .01), and triglyceride (r = -0.18, P < .01) levels, and positively correlated with HDL-C (r = 0.37, P < .01). Sex, age, BMI, and HDL-C (P < .01 for each) were found to be independent factors associated with plasma adiponectin levels in multivariate analysis. Hypoadiponectinemia is significantly associated with cardiovascular risk factors such as insulin resistance and atherogenic lipid profiles in nonobese, apparently healthy subjects.     

Distribution of abdominal adiposity and cardiovascular risk factors in yaquis indians from sonora, méxico

Background: Studies on adiposity in indigenous populations from Mexico are scarce and there are not previous reports that examine the topography of abdominal fat depot and cardiovascular risk factors. Therefore, we determined the distribution of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), and analyzed its relationship with cardiovascular risk factors, in Yaqui Indians. Methods: In a cross-sectional population based study, a total of 82 apparently healthy Yaqui Indians (age 44 +/- 14 years and BMI 27.9 +/- 4.2 kg/m(2)) were randomly enrolled from Vicam, Bacum, and Potam, traditional Yaqui communities from Sonora, in northwest Mexico. Anthropometric parameters, single-slice computed tomography scans at the L(2)-L(3) intervertebral space, fasting glucose, insulin, and lipid profile were assessed. Results: A total of 49 (59.7%) individuals were obese, showing a predominant area of abdominal SAT (319.5 +/- 118.2 cm(2)) over abdominal VAT (134.6 +/- 58.4 cm(2)). Both abdominal VAT (r = 0.54, P = .001; and r = 0.36, P = .01) and SAT (r = 0.15, P = .001; r = 0.47, P = .01) were positively correlated with age and BMI. Abdominal VAT was positively correlated with insulin (r = 0.69, P = .0001) and triglycerides levels (r = 0.42, P = .01). Conclusions: Among Yaquis Indians, obesity with predominant abdominal SAT is common and hyperinsulinemia is the most frequent cardiovascular risk factor. Abdominal VAT, but not abdominal SAT, was related to hyperinsulinemia and hypertriglyceridemia.     

Reliability of the measurement of postprandial thermogenesis in men of three levels of body fatness.

To determine the reliability of the measurement of postprandial thermogenesis by indirect calorimetry and to clarify further the relationship of obesity to thermogenesis in men, the thermic effect of a 720-kcal, mixed liquid meal was compared in 13 lean men (mean +/- SEM, 11.2% +/- 1.4% body fat), 10 average men (22.4% +/- 1.6% body fat), and 12 obese men (33.4% +/- 1.6% body fat) on two occasions. Resting metabolic rate (RMR) was measured for 3 hours: (1) in the fasted state, and (2) after a 720-kcal mixed liquid meal, on two occasions. The thermic effect of the meal, calculated as the postprandial energy expenditure minus the fasting RMR (kcal/3h), was greater for the lean and average men than for the obese men during both trials (P less than .001), but was only marginally different between the lean and average groups (P = .16). The mean values for the two trials were similar and the measurement of thermogenesis was highly reproducible with a reliability coefficient of r = .932 (P less than .001). Across all groups, thermogenesis correlated strongly with percent body fat (r = -.64, P less than .01), but within the average men, thermogenesis was uncorrelated with percent body fat (r = .09) but highly correlated with the glucose response to the meal (r = -.75, P less than .05). Thus, factors other than body fatness, such as insulin sensitivity, may determine thermogenesis within this heterogeneous middle group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Leptin in postmenopausal women: influence of hormone therapy, insulin, and fat distribution

Whether use of hormone-replacement therapy (HRT) influences menopause-related changes in body weight is unclear. HRT may affect energy balance by influencing synthesis of the adipocyte-derived hormone leptin. The objectives of this study were to: 1) identify factors influencing circulating leptin in postmenopausal women; 2) determine whether HRT influences serum leptin after adjusting for confounding factors; and, 3) identify potential independent effects of HRT or leptin on resting energy expenditure (REE). Subjects were 54 postmenopausal women, 45-55 yr old, 35 of whom used HRT (estrogen plus progestin). Total and regional body composition and fat distribution were determined by dual-energy x-ray absorptiometry and computed tomography; fasting serum leptin and insulin, by RIA; and REE, by indirect calorimetry. Stepwise multiple linear regression analysis indicated that serum leptin could best be predicted from total fat mass, fasting serum insulin, and total lean mass [log leptin = 1.08 x log fat mass) + (0.46 x log insulin) + (-1.25 x log lean mass) + 1.88; model R2 = 0.78, P < 0.001]. Multiple linear regression analysis indicated that visceral fat was independently related to leptin (parameter estimate = 0.23, P < 0.05), after adjusting for s.c. abdominal fat and leg fat, as well as lean mass and insulin. After adjusting for total fat mass, total lean mass, and fasting insulin, serum leptin did not differ between users and nonusers of HRT (21.7 +/- 1.0 vs. 20.2 +/- 1.3 ng/mL, P = 0.369, adjusted mean +/- SE, respectively). Serum estradiol was inversely correlated with (adjusted) leptin in non-HRT users (r = -0.50), suggesting that ovarian senescence may lead to an increase in leptin. Multiple linear regression analysis indicated that REE (adjusted for fat mass, fat-free mass, and ethnicity) was not associated with leptin (P = 0.298) or hormone use status (P = 0.999; 1323 +/- 31 vs. 1316 +/- 42 kcal/day, adjusted mean +/- SE for users and nonusers, respectively). These results indicate that, in postmenopausal women: 1) total fat mass, lean mass, and fasting insulin, but not HRT, are significant determinants of serum leptin; 2) visceral and s.c. fat contribute to serum leptin; and, 3) neither HRT nor leptin is independently related to REE.     

Relationship between visceral fat accumulation and anti-lipolytic action of insulin in patients with type 2 diabetes mellitus

Insulin resistance is closely related to developing type 2 diabetes mellitus. Visceral fat accumulation is associated with insulin resistance, which affects the free fatty acid (FFA) metabolism. We investigated the interactions among visceral fat accumulation, FFA metabolism and insulin resistance in 20 patients with type 2 diabetes mellitus, including 11 obese and 9 non-obese subjects. Body fat distribution was estimated by measuring the areas of both subcutaneous and visceral fat mass on abdominal computed tomography at the umbilical level. Glucose infusion rate (GIR) and plasma FFA responses to insulin were determined as an index of insulin resistance and anti-lipolytic action, respectively, in a euglycemic hyperinsulinemic clamp study. There was an inverse correlation between GIR and insulin-induced decrease in plasma FFA in all diabetic patients (r = -0.652, P < 0.01). Visceral fat mass area was well correlated with GIR (r = -0.583, P < 0.01) and insulin-induced decrease in plasma FFA (r = 0.724, P < 0.001), whereas subcutaneous fat mass area was not correlated either with GIR or plasma FFA decrease. These findings suggest that visceral fat accumulation results in increasing the resistance against the anti-lipolytic action of insulin, and that FFA metabolism is closely related with glucose utilization in patients with type 2 diabetes mellitus.     

Hyperglycemia alters tumor necrosis factor-alpha release from mononuclear cells in women with polycystic ovary syndrome

CONTEXT: Women with polycystic ovary syndrome (PCOS) are often insulin resistant and have chronic low-level inflammation. OBJECTIVE: The purpose of this study was to determine the effects of hyperglycemia on lipopolysaccharide (LPS)-stimulated TNFalpha release from mononuclear cells (MNC) in PCOS. DESIGN: The study was designed as a prospective controlled study. SETTING: The study was carried out at an academic medical center. PATIENTS: Sixteen reproductive age women with PCOS (eight lean, eight obese) and 14 age-matched controls (eight lean, six obese) participated in the study. MAIN OUTCOME MEASURES: Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose tolerance test (IS(OGTT)). Percentage of truncal fat was determined by dual-energy absorptiometry. TNFalpha release was measured from MNC cultured in the presence of LPS from blood samples drawn fasting and 2 h after glucose ingestion. RESULTS: IS(OGTT) was lower in women with PCOS compared with controls (3.9 +/- 0.4 vs. 6.3 +/- 1.0; P < 0.03) and was negatively correlated with percentage of truncal fat (r = 0.56; P < 0.002). Truncal fat was greater in lean women with PCOS compared with lean controls (29.8 +/- 2.6 vs. 23.8 +/- 2.5%; P < 0.04). The TNFalpha response was different between obese and lean controls (-96.9 +/- 21.2 vs. 24.4 +/- 21.6 pg/ml; P < 0.03) and obese and lean women with PCOS (-94.1 +/- 34.5 vs. 30.4 +/- 17.6 pg/ml; P < 0.002). Fasting plasma C-reactive protein was elevated (P < 0.003) in obese PCOS and obese controls compared with lean controls. CONCLUSION: An increase in abdominal adiposity and increased TNFalpha release from MNC after hyperglycemia may contribute to insulin resistance in lean PCOS patients. In contrast, obese PCOS patients have more profound chronic inflammation, and thus may have LPS tolerance that protects them from relatively mild excursions in blood glucose.     

Gender differences of regional abdominal fat distribution and their relationships with insulin sensitivity in healthy and glucose-intolerant Thais

To determine gender differences of regional abdominal fat distribution and their relationships with insulin sensitivity in healthy and glucose-intolerant Thais, 44 subjects, 22 men and 22 body mass index-matched women, with normal and abnormal glucose tolerance, which included subjects with impaired glucose tolerance and diabetes, were studied. Total body fat and total abdominal fat (TAF) at L1-L4 were measured by dual-energy x-ray absorptiometry. Regional abdominal fat, which consists of sc abdominal fat and visceral abdominal fat, was determined by single-slice computerized tomography of the abdomen at L4-L5 disc space level. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp and expressed as glucose infusion rate (GIR). With comparable body mass index, visceral abdominal fat was most strongly correlated with GIR after adjustment with percent total body fat in both healthy (r = -0.8155; P = 0.007) and glucose-intolerant women (r = -0.7597; P = 0.011), whereas TAF was most strongly correlated with GIR in both healthy (r = -0.8114; P = 0.008) and glucose-intolerant men (r = -0.6194; P = 0.101). By linear regression analysis, visceral abdominal fat accounted for 35.0% (beta = -3.53 x 10(-2); P = 0.001) of GIR variance in women, whereas TAF accounted for 39.3% (beta = -1.28 x 10(-4); P < 0.0001) of GIR variance in men. We conclude that there are gender differences in the relationships of regional abdominal fat and insulin sensitivity in slightly obese healthy and glucose-intolerant Thais, the difference of which may possibly be in part due to the difference of abdominal fat patterning between genders.