Insulin Resistance Homeostasis Model Research Articles

Serum and adipocyte resistin in polycystic ovary syndrome with insulin resistance.

The aim of this study was to investigate the relationship between resistin and insulin resistance in patients with polycystic ovary syndrome (PCOS). We compared serum resistin levels in 17 PCOS women and 10 lean, healthy, age-matched non-PCOS women and also compared levels of insulin receptor (IR), phosphatidylinositol-3 kinase (PI3-kinase), glucose transporter 4 (GLUT4) protein and resistin mRNA in adipocytes isolated from the omental adipose tissue of five of the PCOS patients and five age- and weight-matched, non-PCOS controls, to look for local defects in insulin action in PCOS. The PCOS group was hyperinsulinaemic and displayed an impaired insulin response in a 75 g oral glucose tolerance test and an abnormal homeostasis model insulin resistance index. Serum resistin levels were similar in PCOS patients and controls; however, resistin mRNA levels were 2-fold higher in adipocytes from PCOS patients. No correlation was found between serum resistin levels and either the BMI or testosterone levels. Western blot analysis showed that adipocyte levels of insulin receptor, PI3-kinase, and GLUT4 were respectively decreased by 56, 39.4 and 54% in PCOS patients compared with controls. These results suggest that overexpression of the resistin gene in adipocytes may be a local determinant factor in the pathogenesis of PCOS.

Altered cortisol metabolism in polycystic ovary syndrome: insulin enhances 5alpha-reduction but not the elevated adrenal steroid production rates.

Androgen excess in women with polycystic ovary syndrome (PCOS) may be ovarian and/or adrenal in origin, and one proposed contributing mechanism is altered cortisol metabolism. Increased peripheral metabolism of cortisol may occur by enhanced inactivation of cortisol by 5alpha-reductase (5alpha-R) or impaired reactivation of cortisol from cortisone by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) resulting in decreased negative feedback suppression of ACTH secretion maintaining normal plasma cortisol concentrations at the expense of androgen excess. We have tested whether any enzyme dysregulation was related to circulating insulin or androgen concentrations in women with PCOS and have sought to clarify their relationship with obesity. First, to avoid obesity-related effects on cortisol metabolism, 18 lean women with PCOS were compared with 19 lean controls who were closely matched for body mass index (BMI). Second, the impact of obesity was studied in a cross-section of 42 PCOS women of a broad range of BMI. We measured 24-h urinary excretion of steroid metabolites by gas chromatography/mass spectrometry and fasting metabolic and hormone profiles. Urinary excretion of androgens [androsterone (P = 0.003), etiocholanolone (P = 0.02), and C19 steroid sulfates (P = 0.009)], cortisone metabolites [tetrahydrocortisone (THE) (P = 0.02), alpha-cortolone (P < 0.001), beta-cortol + beta-cortolone (P < 0.001), cortolones (P < 0.001), and E metabolites (P < 0.001)], and TCM (P = 0.002) were raised in lean PCOS subjects when compared with controls. A significantly higher 5alpha-tetrahydrocortisol (5alpha-THF)/5beta-THF ratio (P = 0.04) and a significantly lower alpha-THF + THF + alpha-cortol/THE + cortolones ratio (P = 0.01) were found in lean PCOS women compared with lean controls, indicating both enhanced 5alpha-R and reduced 11beta-HSD1 activities. A decreased THE/cortolones ratio (P = 0.03) was also found in lean PCOS women compared with lean controls, indicating increased 20 alpha/beta-HSD activity. In the group of 42 PCOS subjects, measures of 5alpha/5beta reduction were positively correlated with the homeostasis model insulin resistance index (HOMA-R): alpha-THF/THF and HOMA-R (r = 0.34; P = 0.03), androsterone/etiocholanolone and HOMA-R (r = 0.32; P = 0.04), and total 5alpha /total 5beta and HOMA-R (r = 0.37; P = 0.02). A positive correlation was also found between measures of 5alpha-R and BMI (r = 0.37; P = 0.02). No correlation was found between measures of 11beta-HSD1 activity and indices of insulin sensitivity or BMI. We have demonstrated that there is an increased production rate of cortisol and androgens as measured in vivo in lean PCOS women. Insulin seems to enhance 5alpha reduction of steroids in PCOS but was not associated with the elevated cortisol production rate. The changes in 5alpha-R, 11beta-HSD1, and 20alpha/beta-HSD enzyme activities observed in PCOS may contribute to the increased production rates of cortisol and androgens, supporting the concept of a widespread dysregulation of steroid metabolism. This dysregulation does not seem to be the primary cause of PCOS because no correlation was found between serum androgen levels or urinary excretion of androgens with measurements of either 5alpha-R or 11beta-HSD1 activities.

Hypertension among HIV patients

Objectives Metabolic syndrome is a cluster of risk factors, such as central obesity, dyslipidemia, glucose intolerance, hypertension, related to insulin resistance. In HIV patients insulin resistance and several metabolic abnormalities of the metabolic syndrome have been described, but few and conflicting studies have investigated the behaviour of blood pressure. The aims of the present study were to evaluate the prevalence of hypertension in a large group of HIV-patients on highly active antiretroviral therapy (HAART) and to investigate the relationship between hypertension, metabolic syndrome and insulin resistance. Design Case control study Methods We enrolled 287 HIV-positive patients on HAART (mean age 41.1 ± 7.5 years) and 287 age- and sex-matched controls. Insulin resistance was estimated by the homeostasis model insulin resistance assessment (HOMA) index. Metabolic syndrome was defined according to the European Group for the Study of Insulin Resistance. Results HIV patients showed a prevalence of subjects with hypertension (34.2 versus 11.9%; P < 0.0001) and metabolic syndrome (33.1 versus 2.4%; P < 0.0001) higher than controls. HOMA was higher in HIV-patients than controls (3.3 ± 1.2 versus 2.0 ± 0.9; P < 0.0001). HOMA (3.7 ± 1.0 versus 3.1 ± 1.2; P < 0.001) and the prevalence of subjects with the metabolic syndrome (64.3 versus 16.9%; P < 0.0001) were greater in HIV-patients with than in those without hypertension. Multiple logistic regression analysis showed that family history of hypertension (odds ratio [(OR): 8.73; 95% confidence interval (CI): 4.31–17.70; P < 0.0001], metabolic syndrome (OR: 6.79; 95% CI: 3.27–14.10; P < 0.0001), lipodystrophy (OR: 4.80; 95% CI: 2.43–9.85; P < 0.0001) and HOMA (OR: 4.13; 95% CI: 1.14–14.91; P < 0.05) were predictors of hypertension in HIV-patients. Conclusions The present study shows that hypertension is frequent in HIV patients on HAART and that hypertension appears to be linked to insulin resistance; in particular, hypertension seems to be a part of the metabolic syndrome.

Postprandial Lipemia in Hypertension

Objective: Many studies have shown that patients with coronary artery disease have an exaggerated rise and a delayed fall of plasma triglyceride (TG) concentration postprandially. We examined whether patients with essential hypertension have the same response to a fatty meal.Methods: A fatty meal (350g per 2 m2 body surface with 83.5% fat) was given to 25 patients with essential hypertension (H) and to 25 normotensives (N). The two groups were matched for age, body mass index, lipid profile, basal glucose and insulin concentrations, and an index of homeostasis model of insulin resistance (HOMA-IR). A quantitative insulin sensitivity check index (QUICKI) was calculated. Blood samples were taken at 0, 4, 6, and 8 hours after the fatty meal. Lipid variables were measured in all samples. Blood glucose and insulin levels were measured in the fasting state.Results: Total and high density lipoprotein cholesterol, apolipoprotein A1 and B, lipoprotein (a), HOMA-IR and QUICKI did not differ significantly over time between the groups. The plasma TG concentration (mg/dL) increased significantly after fat loading in H (from 118 ± 31 to 284 ± 137 at 4 hours, 327 ± 93 at 6 hours and 285 ± 71 at 8 hours) compared to N group (from 105 ± 29 to 150 ± 38 at 4 hours, 148 ± 40 at 6 hours and 115 ± 34 at 8 hours), p = 0.001, p < 0.001 and p < 0.001, respectively.Conclusion: This study suggests that patients with hypertension have an exaggerated response and delayed clearance of plasma TG concentration after fat loading.

Evaluation of circulating levels and renal clearance of natural amino acids in patients with Cushing's disease.

Although the hypercortisolism-induced impairment of protein homeostasis is object of several studies, a detailed evaluation of the complete amino acid profile of patients with Cushing's syndrome (CS) has never been performed. The aim of the current open transversal controlled study was to evaluate serum and urinary concentrations as well as renal clearance of the complete series of natural amino acids and their relationship with glucose tolerance in patients with Cushing's disease (CD). Twenty patients with CD (10 active and 10 cured) and 20 sex- and age-matched healthy controls entered the study. Measurement of serum and urinary levels of the complete series of natural amino acids was performed in all patients analyzed by cationic exchange high performance liquid cromatography (HPLC) after 2 weeks of a standardized protein intake regimen. The renal clearance (renal excretion rate) of each amino acid was calculated on the basis of the serum and urinary concentrations of creatinine and the specific amino acid. Fasting glucose and insulin levels, glucose and insulin response to standard glucose load, insulinogenic and homeostasis model insulin resistance (Homa-R) indexes were also evaluated and correlated to the circulating levels and renal clearances of each amino acid. Significantly higher serum (p<0.01) and urinary (p<0.05) levels of alanine and cystine, lower serum and higher urinary levels of leucine, isoleucine and valine (p<0.05) and higher renal excretion rates of leucine, isoleucine and valine (p<0.01) were found in patients with active CD than in patients cured from the disease and in controls. No difference was found between cured patients and controls. Creatinine clearance was similar in active and cured patients and in controls. In patients with active CD, urinary cortisol levels were significantly correlated to urinary cystine levels (r=0.85; p<0.01) and renal excretion rate of leucine (r=-0.76; p<0.05), isoleucine (r=-0.76; p<0.05) and valine (r=-0.66; p<0.05). Fasting blood glucose levels were significantly correlated to serum alanine levels (r=0.70; p<0.05). Although Homa-R was significantly correlated to BMI in active patients (r=0.74 p<0.05), it was not correlated to amino acid levels. In conclusion, the results of the current study demonstrate that patients with CD have significant changes in serum and urinary concentration of several amino acids and changes in renal clearance of some specific amino acids. Normalization of cortisol levels restored the amino acid profile.

Altered circadian blood pressure profile in patients with active acromegaly. Relationship with left ventricular mass and hormonal values.

To determine the relationships between the circadian blood pressure profile and left ventricular mass, hormonal pattern and insulin sensitivity indices in patients with active acromegaly, ambulatory 24-h blood pressure monitoring (ABPM) was recorded in 25 subjects (47.0 +/- 15.1 years, range 23-72). Serum growth hormone (GH) and insulin-like growth factor-1, fasting and mean plasma glucose and insulin during oral glucose tolerance test (OGTT), insulinogenic index, the sum of the plasma insulin levels and the homeostasis model insulin resistance index (Homa's index) were determined. Left ventricular mass index (LVMI) was calculated from two-dimensional guided M-mode echocardiogram. The prevalence of hypertension was 56% (n = 14) and 40% (n = 10) according to sphygmomanometric measurements and ABPM, respectively. Non-dipping profile was observed in six of 10 hypertensives and in six of 15 normotensives. Serum growth hormone, fasting glucose, the area under the serum insulin curve and LVMI were higher for acromegalics with non-dipping profile than for dippers (all of them, P < 0.05). In non-dippers daytime heart rate was higher than night time (P < 0.001). In conclusion, the main observations in the present study suggested that both normotensive and hypertensive acromegalics had a highly prevalent non-dipping profile with a preserved circadian pattern of heart rate, that was associated with higher levels of serum GH. The disturbance in nocturnal blood fall in normotensives was associated with a decreased insulin sensitivity. The role of GH in blood pressure circadian rhythm regulation in essential hypertension deserves further studies.

Sibling-based association study of the PPARgamma2 Pro12Ala polymorphism and metabolic variables in Chinese and Japanese hypertension families: a SAPPHIRe study. Stanford Asian-Pacific Program in Hypertension and Insulin Resistance.

The peroxisome proliferator activated receptor (PPAR) gamma2 is a transcription factor that has been shown to be involved in adipocyte differentiation, adipogenesis, and insulin sensitivity. To address the role of PPARgamma2 in glucose homeostasis and insulin sensitivity, among many other objectives, we conducted a sibling-controlled association study in a multicenter program - the Stanford Asian-Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe). Approximately 2525 subjects in 734 Chinese and Japanese families have been recruited from six field centers for SAPPHIRe. In total, 1702 subjects including parents and siblings from 449 families have been genotyped for PPARgamma2, of which 328 families were Chinese and 121 Japanese. Only 88 subjects of the 1525 siblings screened for the P12A polymorphism were found to be carriers of the A variant, the most common variant of the PPARgamma2 gene. A variant frequencies of the siblings were 4.27% in Chinese and 2.72% in Japanese. A sibling-controlled association study was performed through genetically discordant sibships (i.e., P/P genotype vs. P/A + A/A genotypes). Specifically, we examined whether there were differences in metabolic variables between the discordant siblings within families. In total, 88 subjects carrying either 1 or 2 A alleles had at least one sibling who was discordant for the P12A polymorphism, yielding a total of 180 individuals from 47 families for analyses, among which 92 siblings were homozygous for wild-type P allele. Siblings with the A variant tended to have lower levels of fasting plasma glucose (OG-10), and lower glucose levels at 60 min following oral glucose loading after adjusting for age, gender, and body mass index. Using a mixed model treating family as a random effect, we found that P12A polymorphism of the PPARgamma2 gene contributes significantly to the variance in fasting plasma glucose, glucose level at 60 min, and insulin-resistance homeostasis model assessment. Our results suggest that within families siblings with the A variant in the PPARgamma2 gene may be more likely to have better glucose tolerance and insulin sensitivity independent of obesity in Chinese and Japanese populations.

Role of diabetes in influencing leptin concentration in elderly overweight patients

Leptin, the product of the ob gene, could have a significant role in the pathogenesis of obesity and non-insulin-dependent diabetes mellitus. However, it is still debated whether different degrees of glucose tolerance may affect plasma leptin concentrations in obese patients. To investigate whether diabetes might influence leptin concentrations in obese patients. We evaluated clinical parameters, anthropometric measures, and sex hormones, fasting plasma leptin, glucose and insulin concentrations in 100 elderly obese diabetic patients and 100 obese non-diabetic control individuals matched for age and sex. After adjustment for age and fat mass, plasma leptin concentrations did not differ between diabetic and non-diabetic obese individuals, in both men and women. In all patients leptin was significantly related to body mass index, fat mass and the homeostasis model insulin resistance index; moreover we observed a significant relationship with fasting plasma glucose and age in diabetic obese women, and with blood pressure values and testosterone concentrations in diabetic obese men. Multiple regression analysis revealed age and fasting plasma glucose to be the only independent determinants of fasting plasma leptin in diabetic obese women. These data suggest that leptin concentrations do not differ between obese diabetic and obese non-diabetic elderly patients. Among correlates of the metabolic syndrome, systolic pressure seems to be related to leptin only in men. In the postmenopausal or andropausal status, sex hormones are related to leptin concentrations only in diabetic men; in diabetic women, however, high glucose seems to be relevant in maintaining the same leptin concentrations as in non-diabetic women with similar degree of obesity.

Body weight, 24-hour blood pressure profile and insulin resistance in lean and overweight hypertensives and normotensive controls

The aim of the study was to examine the relationship between body weight, circadian blood pressure profile, pulse pressure and insulin resistance. The participants were divided into a lean group with a BMI<26 and the overweight group with a BMI ≥26. Sixty-five overweight and 55 lean subjects (age 50.5±14.4 and 49.9±14.4 y, respectively) were included. Ninety five were hypertensives (SBP ≥140 mm Hg and/or DBP≥90 mm Hg on three office measurements). They were kept off antihypertensive agents for at least 3 weeks before the study and then assigned to 24-hour ambulatory blood pressure monitoring (ABPM) and a 2-hour oral glucose (75g)-tolerance test (OGTT). We determined fasting glucose, insulin, and after glucose ingestion. Insulin resistance was estimated by fasting insulin, fasting insulin/glucose ratio, the areas under the curve (AUC) of insulin and insulin/glucose ratio, the homeostasis model insulin resistance index (Homa's index) and the sum of plasma insulin levels 0,30,60, and 120min after the OGTT (ΣIRI). Overweight subjects presented higher waist: hip ratio (0.897±0.090 vs 0.843±0.075, P<.001), AUCInsulin (78.8±56.3 vs 54.5 ± 38.9μU/ml, P<.01), ΣIRI (269.4±197.3 vs 186.6±135.1μU/ml, P<.01), Homa's index (5.22±3.97 vs 3.06±3.21, P<.05), SBP load (% of 24-hour SBP>140 mm Hg) (62.8 ±24.9 vs 51.0±29.6 %, P<.01), and pulse pressure (64.9±13.3 vs 60.4±13.7 mm Hg, P<.01). Nondippers (n=41) compared with dippers presented higher pulse pressure (70.4 ± 12.8 vs 59.0±12.4 mm Hg, P<.001), waist: hip ratio (0.894 ±0.088 vs 0.860 ±0.086, P<.01), AUCInsulin (82.7±54.3 vs 52.4±39.2μU/ml, P<.01) and Homa's index (5.37±3.72 vs 3.12±3.17, P<.01). Correlations of blood pressure and insulin resistance indexes were no significant. BMI was positively related to AUCInsulin (r=0.358), ΣIRI (r=0.338) and Homa's index (r=0.262), all of them P<.01. In conclusion, these date indicate that among normotensive and hypertensive overweight subjects the prevalence of insulin resistance, SBP load and wide pulse pressure were higher than in lean subjects, and that insulin resistance may have some relationship with nondipper profile.

Peripheral blood mitochondrial DNA content is inversely correlated with insulin secretion during hyperglycemic clamp studies in healthy young men

Abnormalities in mitochondrial DNA(mtDNA) have been implicated in the pathogenesis of diabetes mellitus. We recently reported that decreased mtDNA content precedes the development of diabetes mellitus and is associated with parameters of insulin resistance. In this study, we examined whether there is any relation between mtDNA content and insulin secretion. We compared the mtDNA content of peripheral blood leukocytes with the parameters of insulin secretion measured by hyperglycemic clamp in a group of healthy young men. There were statistically significant correlations between mtDNA content in peripheral blood and fasting plasma insulin ( r=−0.43, P<0.05) and C-peptide levels ( r=−0.44, P<0.05). MtDNA content also correlated negatively with acute insulin response( r=−0.48, P<0.05), late insulin response ( r=−0.50, P<0.05) during hyperglycemic clamp and insulin secretion after glucagon stimulation ( r=−0.60, P<0.01). mtDNA content in peripheral blood correlated negatively with homeostasis model (HOMA) insulin resistance ( r=−0.45, P<0.05) although it did not correlate with the insulin insensitivity index ( M/ I) during hyperglycemic clamp. In summary, the mtDNA content of peripheral blood correlated negatively with indices of insulin resistance and insulin secretion in healthy young men. The compensatory response of pancreas beta cells to insulin resistance might contribute in part to increased insulin secretion in these subjects.

Effects of the Magenstrasse and Mill operation for obesity on plasma leptin and insulin resistance.

We evaluated the effect of the Magenstrasse and Mill (M & M) operation--a new form of non-banded vertical gastroplasty-on weight loss, plasma leptin levels and insulin resistance. Fasting plasma glucose, leptin and insulin levels were measured in 12 normal controls, 39 morbidly obese patients and 39 patients a median 3 years after the M & M procedure. Insulin resistance was calculated by the homeostasis model insulin resistance index. Body mass index mean (s.d.) decreased significantly (p < 0.0001), from 48(7) to 33(5) kg/m2, after the M & M procedure. Fasting plasma leptin concentration in the morbidly obese group was 37.9(15.4) ng/ml, significantly (p < 0.0001) higher than the control group (12.2(8.4)) and the M & M group (19.1(12.7)) ng/ml. Fasting plasma insulin concentrations were also significantly (p < 0.0001) higher in the morbidly obese group compared with than in the M & M group or in the control group: 35.5(22.3) mU/l, 15.5(7.1) mU/l and 13.6(3.4) mU/l, respectively. Insulin resistance was 9.6(7.2) in the morbidly obese group and 3.5(1.9) in the M & M group (p < 0.0001). This is one of the first studies to show that the decrease in insulin resistance after weight loss achieved by anti-obesity surgery is associated with significantly lower levels of plasma leptin.

Visceral fat accumulation contributes to insulin resistance, small-sized low-density lipoprotein, and progression of coronary artery disease in middle-aged non-obese Japanese men.

Visceral fat accumulation plays an important role in the occurrence of coronary artery disease (CAD) associated with a cluster of multiple risk factors, such as glucose intolerance, insulin resistance and hyperlipoproteinemia. To clarify the detailed features of these factors, based on visceral fat accumulation, the present study examined the relationship between fat distribution and the characteristics of glucose metabolism and serum lipoproteins in middle-aged non-obese Japanese men. First, the influence of visceral fat accumulation on glucose metabolism, insulin sensitivity, and the extent and severity of coronary artery lesions was investigated in 50 subjects with CAD and compared with 15 control subjects without CAD (Study 1) and with the lipoprotein characteristics in 44 subjects without CAD who were not treated with lipid-lowering drugs (Study 2). Body fat distribution was determined by abdominal computed tomography. In Study 1, the visceral fat area (VFA), blood pressure, fasting immunoreactive insulin (FIRI), and the plasma insulin area (PIA) obtained by oral glucose tolerance test in the subjects with CAD were all significantly higher than in the control subjects. The VFA was significantly correlated with FIRI, the homeostasis model of insulin resistance, PIA and steady state plasma glucose (SSPG) concentration as an index for insulin resistance (r=0.57, p<0.001, r=0.49, p<0.01, r=0.36, p<0.01, and r=0.50, p<0.05, respectively). Although the SSPG concentration did not correlate with the coronary atherosclerosis index as a score of the extent and severity of coronary lesions, the VFA was significantly correlated with this index (r=0.43, p<0.01). In Study 2, the VFA had significant positive correlations with serum total cholesterol, triglyceride, and apolipoprotein B and E levels and the cholesterol and triglyceride concentrations of very-low-density lipoprotein, intermediate-density lipoprotein, and low-density lipoprotein (LDL) fractions. There was a negative correlation between the VFA and LDL particle size (r=-0.34, p<0.05). In conclusion, visceral fat accumulation may contribute to the development of CAD through the progression of insulin resistance and the increase of apo B-containing lipoproteins and small-sized LDLs in middle-aged non-obese Japanese men.

Heterogeneous relationship of early insulin response and fasting insulin level with development of non-insulin-dependent diabetes mellitus in non-diabetic Japanese subjects with or without obesity

The aim of this study was to investigate the association of insulin secretion and insulin resistance with the development of non-insulin-dependent diabetes mellitus (NIDDM) in obese (body mass index (BMI) ≥25 kg/m 2) and non-obese Japanese. Subjects were selected from persons participating a health survey, and a 100 g oral glucose tolerant test was performed. A total of 1604 non-diabetic subjects were followed for 2–8 years (mean 4.5 years). The fasting insulin level and the homeostasis model insulin resistance index (HOMA-R=fasting glucose [mmol/l]×fasting insulin [μU/ml]/22.5) were used as the index of insulin resistance, and insulinogenic index (the ratio of increment of insulin to that of blood glucose 30 min after glucose load) as a measure of early insulin response. Cox’s proportional hazards analysis in the whole group showed that BMI, fasting blood glucose (FBG) and 2-h blood glucose (2-h BG) were positive predictors, and age and insulinogenic index were negative predictors of diabetes. Sex, family history, fasting insulin level and HOMA-R were not predictive of developing diabetes. In subgroup analysis, the same variables as in the whole group were predictors in non-obese, whereas only FBG and 2-h BG predicted diabetes in obese subjects. Fasting insulin level and HOMA-R were not predictive of diabetes both in non-obese and obese subjects. Eleven obese subjects, who developed diabetes despite a normal initial insulinogenic index, had significantly higher BMI, fasting insulin level and HOMA-R, compared with 258 obese subjects who did not develop diabetes. We conclude that most cases of diabetes in Japanese begin with decreased insulin secretion, but a small group of diabetes patients may start with insulin resistance, especially obese subjects.

The obese gene product, leptin: possible role in obesity-related hypertension in adolescents.

The mechanism of the association between obesity and hypertension is not clear. The recently discovered obese gene product, leptin, the levels of which increase in obese subjects, has been shown to reduce food intake and increase sympathetic nervous system activity in animal studies. The present study was undertaken to elucidate the relationship between blood pressure and factors related to obesity, including leptin, in different age groups. The subjects were 348 Japanese male adolescents (15-17 years old) and 165 men (40-59 years old) not taking medication for hypertension, diabetes mellitus or hyperlipidaemia. Height, weight, blood pressure, heart rate, plasma glucose, lipid profiles, serum insulin and leptin levels were measured in the morning after an overnight fast Body mass index (BMI), serum leptin level and the homeostasis model insulin resistance index increased in the order of blood-pressure category (i.e. normotensive < high normal < hypertensive) in both the male adolescents and the middle-aged men. In addition, simple linear regressions revealed that both systolic and diastolic blood pressure correlated significantly with serum leptin and the insulin resistance index in both groups. Even after adjustment for age and BMI, the correlation of mean blood pressure with leptin remained in the obese adolescents (r2 = 0.390, P = 0.02). The heart rate also correlated with leptin in the adolescents (r = 0.18, P< 0.001), but not in the middle-aged subjects (r = 0.04). Even after adjustment for age and BMI in adolescents, serum leptin correlated significantly with heart rate. These results suggest a role for leptin in obesity-related hypertension, especially in adolescents.