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)     

Microalbuminuria and other cardiovascular risk factors in nondiabetic subjects.

The association between urinary albumin:creatinine ratio and other cardiovascular risk factors such as age, blood pressure, obesity, glycemic indices, insulin and lipid profile was examined in a population in a Chinese community consisting of 795 men (mean age 35.8 +/- 8.8 yr) and 538 women (mean age 37.9 +/- 8.9 yr) with a normal glucose tolerance defined by WHO criteria. Men with a urinary albumin:creatinine ratio above the 90th percentile had higher systolic and diastolic blood pressures, fasting plasma glucose, 2-h glucose after a 75 g oral glucose load, and fasting serum insulin. Women with high urinary albumin:creatinine values had higher systolic and diastolic blood pressures, body mass index, waist-hip ratio, fasting insulin and triglycerides. Multivariate analysis showed that only systolic blood pressure and fasting glucose in men, and diastolic blood pressure and fasting insulin in women, independently contributed to urinary albumin:creatinine. When the effect of blood pressure was eliminated by excluding subjects with systolic blood pressure > 140 and diastolic > 90 mm Hg, only fasting insulin was associated with urinary albumin:creatinine in women. No associations were found for men. We conclude that microalbuminuria may be a marker for cardiovascular disease only because of its association with blood pressure in men, while in women, there is an additional independent association with fasting serum insulin.     

Evidence for an association of high blood pressure and hyperinsulinemia in obese man

An association between hyperinsulinemia and hypertension has been suggested by epidemiological surveys. To assess whether this association is independent of the presence of other hyperinsulinemic states, such as obesity and glucose intolerance, we measured the insulin response to oral glucose in a group of middle-aged moderately obese [144 +/- 4% overweight (mean +/- SEM)] patients (n = 18) with essential hypertension (174 +/- 5/104 +/- 2 mm Hg) and normal glucose tolerance. Normotensive subjects (n = 17) with normal glucose tolerance, matched for age and degree of overweight, served as the control group. The mean insulin response to glucose was twice as high in the hypertensive patients (25.8 +/- 0.2 mU/ml X 2 h) as in the normotensive subjects (11.3 +/- 0.2; P less than 0.001), yet the glucose incremental area was 3-fold higher in the former (10.9 +/- 1.0 g/dl X 2 h) than in the latter (3.5 +/- 0.7; P less than 0.001), thus indicating more severe insulin resistance. In the hypertensive group, systolic blood pressure levels were directly correlated with the 2-h plasma insulin values (r = 0.75; P less than 0.001). Furthermore, the 2-h plasma insulin value and the degree of overweight accounted for 65% of the variation in the systolic blood pressure in a multiple regression model (r = 0.81; P less than 0.001). We conclude that in obesity, the occurrence of hypertension marks the presence of additional hyperinsulinemia and insulin resistance, independent of any impairment of glucose tolerance.     

A close association between insulin resistance and dehydroepiandrosterone sulfate in subjects with essential hypertension

To examine the serum levels of dehydroepiandrosterone sulfate (DHEAS) and its relation with insulin resistance and the other risk factors in essential hypertension, serum DHEAS and insulin sensitivity were assessed in 35 male hypertensive and 17 male healthy control subjects aged 50-59 years. Fasting plasma insulin and the area under curve of plasma insulin were determined during a 75 g oral glucose tolerance test. Insulin sensitivity was measured by the steady state plasma glucose method. Fasting plasma insulin and the area under curve of plasma insulin were significantly higher in the hypertensive group than in control group. Steady state plasma glucose was significantly higher in hypertensive subjects indicating insulin resistance compared with control subjects. On the other hand, fasting serum DHEAS levels were significantly lower in the hypertensive group than in the control group. Fasting serum DHEAS levels were inversely correlated with steady state plasma glucose significantly (p=0.0008), indicating a close association between DHEAS levels and insulin resistance. Fasting serum DHEAS was inversely correlated with systolic blood pressure and fasting plasma insulin. In multiple regression analysis of hypertensive subjects, steady state plasma glucose was the strongest determinant of the fasting serum level of DHEAS, followed by systolic blood pressure and fasting plasma insulin. These 3 factors accounted for 51.6% of the variation in DHEAS. In nonobese and nondiabetic essential hypertension, serum DHEAS was lower and insulin resistance was the most significant independent determinant of reduced serum DHEAS, followed by systolic blood pressure and fasting plasma insulin.     

Impact of body mass index on blood pressure levels in patients with polycystic ovary syndrome

As there is controversy about the prevalence of hypertension in patients with polycystic ovary syndrome (PCOS) and, up to the present moment, no studies have evaluated the impact of body mass index (BMI) on blood pressure levels (BP) in these patients, we studied retrospectively sixty-nine patients with PCOS, with BMI of 29.0 +/- 6.7 kg/m(2) and aged 25.6 +/-5.6 yr, subdivided into three groups according to BMI (normal, overweight and obese) and evaluated regarding BP (mercury sphygmomanometer), basal hormonal profile, fasting glucose, and insulin sensitivity (HOMA-IR). Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were normal (118.1 +/- 17.0 and 74.7+/- 11.5 mmHg, respectively), with a hypertension prevalence of 20.3%. Of these patients, 78.6% were obese and 21.4% were overweight. When the groups were compared according to BMI, a significant increase in SBP and DBP was observed (higher in overweight and obese patients for SBP and higher in obese for DBP), as well as a significant progressive increase in glucose, insulin, homeostatic model assessment, and a significant progressive decline in LH levels. When the patients were subdivided as normotensive or hypertensive, a significant difference was observed only for BMI (28.2 +/- 6.1 and 34.7 +/- 8.6 kg/m(2), respectively; p = 0.007). In conclusion, we observed a significant and progressive impact of BMI on blood pressure levels in our patients with polycystic ovary syndrome.     

Fasting serum insulin levels in essential hypertension. A meta-analysis.

BACKGROUND--The role of insulin in the genesis of essential hypertension remains an area of intense controversy. Most clinical evidence suggests a definite association. Several pathophysiologic mechanisms have been proposed. However, current data remain disparate and contradictory. METHODS--Meta-analysis allows data pooling of primary study findings and subsequent integration into a statistically meaningful outcome. This method was used to study the relationship in euglycemic individuals between blood pressure and fasting serum insulin level, age, body mass index, and fasting plasma glucose level. RESULTS.-A significant correlation was demonstrated between fasting serum insulin concentration and both systolic blood pressure and diastolic blood pressure. Age and body mass index also revealed meaningful associations. The meta-analytic correlation between plasma glucose level and both systolic blood pressure and diastolic blood pressure failed to achieve significance. CONCLUSIONS--Data from a meta-analytic review examining fasting serum insulin levels in euglycemic individuals demonstrate a significant correlation with systolic and diastolic blood pressure. This study supports the role of hyperinsulinemia in the pathogenesis of essential hypertension.     

Lack of association between blood pressure and insulin in patients with insulinoma

To investigate the hypothesis that insulin affects the regulation of blood pressure, blood pressure and fasting insulin and glucose levels were measured in seven patients with insulinoma both before and after resection of the insulinoma. The diagnosis of all insulinoma cases was confirmed during surgery. Before surgery, systolic and diastolic blood pressures were 127 +/- 15 and 74 +/- 9 mmHg, respectively, and did not correlate with the fasting insulin levels. At least 3 weeks after the surgery, significant decreases in fasting insulin levels (from 568 +/- 571 to 74 +/- 43 pmol/l, P less than 0.005) and body weight (-9.8 +/- 7.1%, P less than 0.05) were observed along with a significant increase in fasting glucose levels (98.2 +/- 43.2%, P less than 0.001). However, both systolic (-4.7 +/- 9.9%) and diastolic (-0.2 +/- 6.3%) blood pressures remained unchanged. The changes in fasting insulin levels were not linearly correlated with those in systolic and diastolic blood pressures. Even after the changes in both body weight and fasting glucose levels were taken into consideration using partial correlations, the changes in fasting insulin levels did not correlate with those in systolic and diastolic blood pressures. It was concluded that blood pressure, both systolic and diastolic, was not at hypertensive levels in the patients with insulinoma and showed no decrease after resection of the insulinoma. Therefore, insulin may not affect the regulation of blood pressure in patients with insulinoma.     

High plasma leptin concentrations in hypertensive men but not in hypertensive women.

OBJECTIVE: Previous studies on humans have reported higher leptin levels in women than in men, independent of body fat, and leptin has been correlated with insulin resistance in men but not in women. Since insulin resistance is thought to play a role in raising blood pressure, we investigated sex differences in leptin concentrations between hypertensive and normotensive individuals. METHODS: Ninety-two nondiabetic hypertensive patients (48 men and 44 women) and 92 age, body mass index (BMI)-matched normotensive control individuals were studied. Fasting plasma glucose, insulin, leptin and lipoprotein concentrations, glucose and insulin responses to 75 g oral glucose tolerance test (OGTT) and insulin suppression tests were determined. RESULTS: Fasting plasma leptin concentrations were higher in hypertensive men than in normotensive men (5.1 +/- 0.5 versus 3.9 +/- 0.4 ng/ml, P = 0.015). However, fasting plasma leptin concentrations were not significantly different between hypertensive and normotensive women (11.8 +/- 1.0 versus 10.9 +/- 1.0 ng/ml, P = 0.440). Fasting plasma leptin concentrations showed good correlation with BMI, body fat, fasting plasma insulin concentrations, and insulin area to OGTT in both men and women (all P < 0.001). However, fasting plasma leptin concentrations were related to steady-state plasma glucose (SSPG) concentrations, a measure of insulin sensitivity by insulin suppression test, in men only (P < 0.001). After adjustment for body fat amount, age and duration of hypertension, fasting plasma leptin levels still correlated significantly with SSPG concentrations in men. These four variables together accounted for a 67.9% variation in fasting plasma leptin levels in men. In women, body fat amount was the only significant determinant for plasma leptin levels. These four variables accounted for a 78.2% variation in plasma leptin levels in women. CONCLUSIONS: Our study confirmed a sex difference in leptin levels both in hypertensive and normotensive subjects. Higher plasma leptin concentrations in hypertensive men but not in hypertensive women when compared with normotensive control individuals was also demonstrated. These observations are consistent with the findings that plasma leptin is correlated with insulin sensitivity in men but not in women. Further studies are needed to understand the causes and consequences of sex effects on leptin in blood pressure regulation.     

Serum Insulin,Insulin Sensitivity,and Erythrocyte Sodium Metabolism in Normotensive and Essential Hypertensive Subjects with and Without Overweight

Increased insulin circulating levels and perturbations of intracellular sodium metabolism have been reported in essential hypertensive patients, leading to postulate their involvement in the pathophysiology of the disease. In-vitro studies have shown that insulin modulates the activity of some transmembrane sodium transporters. The aim of this investigation was to assess in subjects with essential hypertension and/or overweight, the levels of fasting serum insulin, the activity of sodium transporters and their possible relationships. In 18 lean normotensive, 12 overweight normotensive, 18 untreated lean essential hypertensive, and 16 untreated overweight essential hypertensive subjects, we measured the fasting levels of blood glucose and serum insulin, and calculated the glucose/insulin ratio as an index of sensitivity to insulin. In addition, in the red blood cells of these subjects, we evaluated the maximal rate of ouabain-sensitive Na/K pump, furosemide-sensitive outward Na/K cotransport, Na_i/Li_o countertransport, and the constant rate of passive permeabilty to Na. When compared to lean normotensive, overweight normotensive, lean hypertensive, and overweight hypertensive subjects exhibited significantly higher fasting insulin levels, with lower glucose/insulin ratio. No significant difference was found in the activity of Na/K pump, Na/K cotransport, and passive permeability to Na. The Na_i/Li_o exchange was significantly increased in both hypertensive groups. Mean blood pressure correlated positively and independently with body mass index and fasting insulinemia, and inversely with the glucose/insulin ratio. No relationships were found between blood pressure, fasting insulin levels or glucose/insulin ratio and the activity of sodium transport systems. We conclude that hyperinsulinemia and insulin resistance are associated with essential hypertension independently of overweight. These data lend support to the hypothesis that insulin is involved, concurrently with other factors, in the pathogenesis of essential hypertension in both lean and obese subjects.     

Obesity worsens cardiovascular risk profiles independently of hyperinsulinaemia

OBJECTIVE: To investigate whether human obesity is characterized by a worse cardiovascular risk profile (than no obesity) even in the absence of hyperinsulinaemia. SUBJECTS AND DESIGN: A total of 367 healthy subjects (247 nonobese and 120 obese) with normal glucose tolerance and without family history of diabetes mellitus. INTERVENTIONS: A 75-g oral glucose tolerance test was performed in all participants. MAIN OUTCOME MEASURES: Anthropometry, blood pressure, fasting plasma lipids and urate, plasma glucose and insulin concentrations at fasting, 1 h and 2 h after oral glucose load. RESULTS: In a multivariate linear regression analysis, body mass index was strongly related to all cardiovascular risk factors, independently of sex, age and plasma insulin. When risk factors were compared in 37 normoinsulinaemic obese subjects (plasma insulin within one standard deviation of the mean values observed in the 247 nonobese subjects), and in 37 sex- and age-matched normoinsulinaemic nonobese subjects, we found that plasma glucose levels were similar in the two groups, whereas plasma triglyceride (1.50 +/- 0.13 vs. 1.13 +/- 0.08 mmol L-1; mean +/- SE), low-density lipoprotein cholesterol (3.42 +/- 0.25 vs. 2.77 +/- 0.18 mmol L-1) and urate (290 +/- 12 vs. 255 +/- 12 mumol L-1) levels were significantly higher, and plasma high-density lipoprotein cholesterol concentrations were lower (1.27 +/- 0.04 vs. 1.46 +/- 0.06 mmol L-1) in obese than in nonobese subjects with normal plasma insulin levels (P < 0.01). Also systolic (132 +/- 2 vs. 124 +/- 2 mmHg) and diastolic (86 +/- 1 vs. 81 +/- 1 mmHg) blood pressure values were significantly higher in normoinsulinaemic obese subjects than in normoinsulinaemic nonobese individuals (P < 0.001). CONCLUSIONS: These results suggest that in human obesity a worse cardiovascular risk profile is found (than in the nonobese) independently of the presence of hyperinsulinaemia.     

Surrogate indexes vs. euglycaemic-hyperinsulinemic clamp as an indicator of insulin resistance and cardiovascular risk factors in overweight and obese postmenopausal women

BACKGROUND: There is considerable interest in validating the most convenient method to estimate insulin sensitivity in clinical research protocols that could best indicate cardiovascular risk factors. To address this issue we examined the interrelationships of several cardiovascular risk factors with surrogate indexes such as fasting insulin, the homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI) and the revised QUICKI vs the euglycaemic-hyperinsulinemic (EH) clamp in a non-diabetic overweight or obese postmenopausal female population. DESIGN: Cross-sectional study involving 88 obese postmenopausal women (age: 57.5+/-5.0 yrs; body mass index: 32.52+/-4.4 kg/m2; percent body fat: 46.35+/-4.9%). METHODS: Insulin sensitivity was determined by the EH clamp technique as well as by surrogate indexes such as fasting insulin, HOMA, log HOMA, QUICKI and revised QUICKI. Body composition and body fat distribution were measured using dual energy x-ray absorptiometry and computed tomography, respectively. RESULTS: Correlations between insulin resistance indexes (fasting insulin, revised QUICKI, QUICKI, log HOMA, HOMA) vs glucose disposal were similar (range of r's=0.40 to 0.49), suggesting that no index was superior to another with respect to its relationship with the EH clamp. Correlations between the insulin resistance indexes with plasma lipids were comparable among all indexes, however, systolic blood pressure, visceral fat and C-reactive protein were moderately superior with index vs the EH clamp. CONCLUSION: Surrogate measures of insulin resistance, in particular fasting insulin, are simple tools appropriate for epidemiological studies that can be used as substitutes for the EH clamp to estimate glucose disposal and cardiovascular risk factors in overweight and obese postmenopausal women.     

Insulin resistance and blood pressure in young black men

Insulin resistance, independent of obesity or non-insulin-dependent diabetes mellitus, has been demonstrated to be associated with high blood pressure. To determine if insulin resistance could be an antecedent to hypertension in a high-risk population, we studied normotensive (112 +/- 12/70 +/- 10 mm Hg) and borderline hypertensive (135 +/- 8/85 +/- 5 mm Hg) lean young black men (22-26 years old) with the euglycemic hyperinsulinemic clamp technique. All subjects had clinically normal oral glucose tolerance. Body mass index and percent adipose mass were the same in both groups. Fasting plasma insulin concentration was significantly higher in the borderline hypertensive group (p less than 0.01). Insulin-directed exogenous glucose metabolism at the same degree of steady-state hyperinsulinemia was significantly lower in the borderline hypertensive group (5.98 +/- 2.22 versus 8.22 +/- 1.96 mg/kg/min; p less than 0.01). For the total population, a significant inverse correlation existed between the glucose infusion rate and systolic blood pressure (p less than 0.01). These data indicate that there is a relation between insulin-mediated glucose uptake and blood pressure. Furthermore, in this high-risk population insulin resistance may precede the onset of established essential hypertension.     

A prospective study of glycemia, body size, insulin resistance and the risk of hypertension in Mauritius

OBJECTIVE: To estimate the associations between new-onset hypertension and glycemia, insulin resistance, and overall and regional adiposity in a prospective study conducted in Mauritius. RESEARCH DESIGN AND METHODS: Three thousand five hundred and eighty-one adults without hypertension, pregnancy, or known diabetes at baseline (1987) were followed for incident hypertension in 1992 and 1998, (systolic blood pressure > or =140 mmHg or diastolic blood pressure > or =90 mmHg or antihypertensive medication treatment). Other measurements included fasting plasma glucose and 2-h plasma glucose after a 75-g oral glucose load, fasting insulin, BMI, waist circumference, smoking, alcohol use, exercise, and demographic information. Insulin sensitivity was estimated by the computerized homeostasis model assessment (HOMA2) program. RESULTS: In multivariable logistic models that included age, gender, ethnicity, alcohol use, exercise, education, systolic blood pressure, diastolic blood pressure, homeostasis model assessment, fasting plasma glucose, 2-h plasma glucose, BMI, and waist circumference, the independent predictors of incident hypertension by time of follow-up were (odds ratio for a 1 SD increase; 95% confidence interval): 1992 - age (1.73; 1.47-2.03), Creole ethnicity (1.42; 1.04-1.94), 2-h plasma glucose (1.26; 1.04-1.51); 1998 - age (1.60; 1.40-1.83) and BMI (1.33; 1.05-1.69). Also, systolic blood pressure and diastolic blood pressure significantly predicted hypertension at both time points. CONCLUSION: Risk factor patterns depended on duration of follow-up. Over 5 years, hypertension was related to 2-h plasma glucose but not to measures of body size or homeostasis model assessment, while over 11 years, incident hypertension was related to BMI but not waist circumference, 2-h plasma glucose, or homeostasis model assessment. These findings support a more important role for 2-h plasma glucose and overall adiposity than waist circumference, fasting plasma glucose, or insulin resistance in the development of hypertension in Mauritius.     

Relationship between blood pressure and plasma insulin in non-obese and obese non-diabetic subjects

Summary In this study, we have measured plasma insulin at fasting and following an oral glucose load and blood pressure after glucose load in 367 (247 non-obese, 120 obese) normotensive and untreated mildly hypertensive subjects. Overall, there was no independent association between fasting plasma insulin levels and blood pressure values. After controlling for age and body weight, a significant relationship between postglucose plasma insulin levels and diastolic blood pressure was found. When non-obese and obese subjects were examined separately, significant relationships were identified between postglucose plasma insulin levels and both systolic and diastolic blood pressure values in the former but not in the latter. A comparison of sex-, age-, and weight-matched hyperinsulinaemic vs normoinsulinaemic subjects showed that the former had significantly higher values of blood pressure only if not obese. These results demonstrate that the plasma insulin response to glucose is independently correlated with blood pressure.     

Insulin and blood pressure in obesity

To assess factors in overweight persons that account for a tendency toward hypertension, 33 very obese women, 26 to 77 years of age, were studied. Blood pressures in these 33 women varied from low normal to mildly hypertensive. None of them had taken medication for high blood pressure, and none had diabetes mellitus. The effect of independent variables--age, body mass index (weight/height2), fasting serum glucose levels, fasting serum insulin levels, and 24-hour urinary sodium excretion--on systolic and diastolic blood pressure was assessed. There was no correlation between sodium excretion and blood pressure. Age did not correlate with diastolic blood pressure but did correlate with systolic blood pressure when body mass index, serum glucose level, and insulin level were controlled. Diastolic blood pressure correlated with body mass index and serum glucose level, but only the latter remained significant when all independent variables were considered together. Both systolic and diastolic blood pressure were found to be significantly related to fasting serum insulin level (r = 0.47, p = 0.005 and r = 0.68, p less than 0.001) even when age, weight, and serum glucose level were controlled (r = 0.41, p = 0.025 and r = 0.62, p less than 0.001 respectively). The relation between serum insulin and blood pressure was more pronounced in those women with a family history of hypertension. These data indicate that insulin may play a major role in the regulation of blood pressure in obesity and that the previously accepted relation of weight to blood pressure may depend on blood levels of insulin.     

The association of brain natriuretic peptide and insulin resistance in obesity-related hypertension

Hypertension is frequently associated with obesity and natriuretic peptide levels are reported to decrease in obese subjects. Both the lower brain natriuretic peptide (BNP) concentration and insulin resistance are suggested to be associated with hypertension. However, their involvement in obesity-related hypertension has not been clearly defined. Forty-four obese women (21 normotensive and 23 hypertensive) and 25 healthy women matched for age were included in the study. Anthropometrical parameters were determined. Serum BNP, fasting insulin and glucose concentrations, and lipid parameters were evaluated. Insulin resistance was calculated using Homeostasis Model Assessment (HOMA) and Quantative Insulin Sensitivity Check Index (QUICKI) formulations. Within the obese groups, HOMA and QUICKI reflected the increased insulin resistance in hypertensive obese subjects with a significant correlation to blood pressure. The decrease in BNP in the obese groups was in favour of the hypertensive obese subjects (31.43+/-6.43; 26.36+/-4.29; and 17.51+/-3.08 pg/ml, respectively) with a fractional statistical significance between the hypertensive obese group and the controls (P=0.047). Only for the obese hypertensive group, fasting glucose, HOMA and QUICKI were significantly correlated with BNP. Moreover, fasting plasma glucose (R(2)=0.22, P=0.007) and fasting plasma insulin (R(2)=0.39, P=0.03) were independently correlated with BNP only for the obese hypertensive group. It can be concluded that the decrease in BNP concentrations in the obese hypertensive subjects seem to be well correlated with the insulin resistance.     

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.     

Insulin resistance and hypertension in postmenopausal women

The aim of the study was to elucidate the role of hyperinsulinaemia/insulin resistance in hypertension of lean postmenopausal women. Twenty-four women with essential hypertension (systolic/diastolic > or =140/90 mm Hg) and a body mass index (BMI) less than 26 kg/m(2) not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period, and 10 normotensive postmenopausal weight- and aged-matched controls were compared. Both groups were not receiving hormone replacement therapy. Hip and waist circumferences were measured and waist/hip ratios were calculated. Casual blood pressure was measured in triplicate. Neither the fasting plasma glucose nor serum insulin levels in hypertensive women and normotensives differed significantly. During 2 h oral glucose (75 g)-tolerance test the mean plasma glucose levels after 30 min (172.5 +/- 40.24 mg/dl vs. 143.67 +/- 20.16 mg/dl), 60 min (134.88 +/- 38.78 mg/dl vs. 112.33 +/- 5.44 mg/dl) and 120 min (116.08 +/- 26.65 mg/dl vs. 95.56 +/- 20.17 mg/dl) were significantly higher in hypertensives than that for normotensives (P < 0.05 for all three comparisons). The mean serum insulin levels of hypertensive women were significantly higher than that in normotensives after 15 min (92.04 +/- 59.90 microU/ml vs. 54.89 +/- 33.67 microU/ml) and 120 min (49.63 +/- 44.45 microU/ml vs. 19.22 +/- 24.10 microU/ml; P< 0.05 for both comparisons). The mean serum insulin: plasma glucose ratio for hypertensive women was significantly higher than that for normotensives after 15 min (0.596 +/- 0.46 vs. 0.359 +/- 0.20 microU/mg), 60 min (0.406 +/- 0.30 vs. 0.329 +/- 0.25 microU/mg) and 120 min (0.436 +/- 0.35 vs. 0.205 +/- 0.26 microU/mg) (P < 0.05 for all three comparisons). Significant correlations were observed between the daytime period and 24-h average ambulatory systolic blood pressure and the area under the serum insulin curve (r = 0.41 and 0.36, respectively). For non-dippers we found higher fasting insulinaemias but the AUC(insulin) did not differ. Plasma glucose levels did not differ either during fasting or during OGTT (AUC(glucose)). Insulinogenic index was higher in dippers than in non-dippers. We conclude that in lean, postmenopausal hypertensive women insulin resistance is increased compared with age- and weight-matched normotensive women. Also, hyperinsulinaemia correlates with ambulatory systolic blood pressure. Thus, insulin resistance may possibly be involved as a pathogenetic factor in lean, postmenopausal hypertensive women.     

Hypertension in obese children: fasting serum insulin levels are closely correlated with blood pressure

The relationship between blood pressure and anthropometric or metabolic factors was studied in 324 obese children aged 9.5 +/- 1.8 years (mean +/- standard deviation). Obese children had a significantly higher blood pressure than non-obese children (systolic blood pressure: 121 +/- 14 mmHg in obese children vs 112 +/- 11 mmHg in non-obese children, P less than 0.001; diastolic blood pressure: 72 +/- 9 mmHg in obese children vs 66 +/- 7 mmHg in non-obese children, P less than 0.001). When the obese children were divided into hypertensive and normotensive groups, there was a significant difference in fasting serum insulin levels between the two groups (19.3 +/- 9.3 microU/ml in the hypertensive group vs 13.0 +/- 6.1 microU/ml in the normotensive group), and a close correlation between fasting serum insulin levels and systolic blood pressure was demonstrated (r = 0.63, P less than 0.001). However, there was no significant correlation between blood pressure and the degree of obesity itself or the waist-to-hip ratio in the obese children. There was no significant correlation between blood pressure and fasting plasma glucose, serum total cholesterol, or triglycerides levels in the obese children. Moreover, the correlation between fasting insulin levels and blood pressure was shown to be independent of the degree of obesity or waist-to-hip ratio and age by multiple regression analysis. These results indicate that hyperinsulinemia itself may play an important role in the pathogenesis of hypertension in obese children.     

Independent association of plasma leptin levels and left ventricular isovolumic relaxation in uncomplicated hypertension.

BACKGROUND: On the basis of evidence of plasma leptin (LE) effects on cardiovascular system, we assessed possible association of LE and Doppler-derived left ventricular (LV) diastolic function in arterial hypertension. METHODS: Doppler echocardiography, blood sample for fasting plasma LE levels, and euglycemic hyperinsulinemic glucose clamp were performed on 15 healthy insulin-sensitive men and 40 newly diagnosed hypertensive men, who were divided into two groups according to insulin sensitivity degree: 15 insulin sensitive (IS) and 25 insulin resistant (IR) individuals (whole body glucose disposal >33.3 and <33.3 micromol/kg, respectively). RESULTS: The IR hypertensives had significantly higher body mass index (BMI), waist/hip ratio, LE and LV mass index than the other two groups. IR hypertensives had lower LE (even after adjusting for BMI and waist/hip ratio) and among LV diastolic indexes, lower E peak velocity (P < .05) and longer isovolumic relaxation time (IVRT) (P < .001) in comparison to IR hypertensives. IR hypertensives had the lowest E/A ratio (0.88 +/- 0.2) compared to IS patients (1.03 +/- 0.1 P < .05) and controls (1.31 +/- 10.2 P < .001). By multiple linear regression analyses performed both in the overall population and hypertensives, LV mass index and LE were independently associated to IVRT (R2 = 0.41 in overall population, R2 = 0.42 in hypertensives, both P < .0001), whereas age, heart rate, diastolic and systolic blood pressure (BP), BMI, waist/hip ratio, and insulin action were not significant. CONCLUSIONS: Our study underscores an independent association of increased plasma LE and lengthening of isovolumic relaxation in uncomplicated hypertension. Further studies will need to understand the conditions underlying both these phenomena.