Blood pressure development and hypertensive retinopathy: 20-year follow-up of middle-aged normotensive and hypertensive men.

Screening for hypertensive organ damage is important in assessing cardiovascular risk in hypertensive individuals. In a 20-year follow-up of normotensive and hypertensive men, signs of end-organ damage were examined, focusing on hypertensive retinopathy. In all, 56 of the original 79 men were reexamined for hypertensive organ damage, including by digital fundus photography. The diameters of the central retinal artery equivalent (CRAE) and vein were estimated and the artery-to-vein diameter ratio calculated. Components of metabolic syndrome were assessed. Fifty percent of the normotensive men developed hypertension during follow-up. Significant differences appeared in CRAE between the different blood pressure groups (P=0.025) while no differences were observed for other markers of hypertensive organ damage. There were significant relationships between CRAE and blood pressure at baseline (r=-0.466, P=0.001) and at follow-up (r=-0.508, P<0.001). A linear decrease in CRAE was observed with increasing number of components of the metabolic syndrome (beta=-3.947, R(2)=0.105, P=0.023). Retinal vascular diameters were closely linked to blood pressures and risk factors of the metabolic syndrome. The diversity in the development of hypertensive organ damage, with changes in retinal microvasculature preceding other signs of damage, should encourage more liberal use of fundus photography in assessing cardiovascular risk in hypertensive individuals.

Long-term plasma catecholamines in patients with hypertension and left ventricular hypertrophy treated with losartan or atenolol: ICARUS, a LIFE substudy.

Hypertension is a major risk factor for morbidity and mortality. Plasma catecholamines are linked to the pathogenesis of hypertension. Pharmacological intervention, including treatment with beta-blockers, reduces cardiovascular mortality and morbidity. In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, the angiotensin receptor blocker losartan significantly reduced cardiovascular end points compared to the beta-blocker atenolol. Thus, for the first time, one drug was shown to be superior to another in hypertension. The present substudy examined the effects of atenolol vs losartan treatment on plasma catecholamines at rest and during hyperinsulinaemia in a cohort of 86 LIFE patients. Plasma adrenaline increased significantly from placebo treatment at baseline to year 1 of treatment (P<0.0001), and also during hyperinsulinaemia (P<0.0001). Plasma noradrenaline did not change significantly from placebo treatment at baseline to year 1, but increased significantly during hyperinsulinaemia both at baseline and at year 1 (P<0.0001 for both). There were no differences in plasma catecholamines or the relative changes between the two treatment arms at any stage. In a subset of 42 patients examined also at years 2 and 3, these findings were confirmed during long-term treatment. Thus, losartan had an effect on plasma catecholamines comparable to that with the beta-blocker atenolol in patients with hypertension and left ventricular hypertrophy at rest and during hyperinsulinaemia. We find it unlikely that a difference in sympathetic activity explains the outcome benefits of losartan over atenolol in the LIFE study.

Are left ventricular mass, geometry and function related to vascular changes and/or insulin resistance in long-standing hypertension? ICARUS: a LIFE substudy.

Vascular hypertrophy and insulin resistance have been associated with abnormal left ventricular (LV) geometry in population studies. We wanted to investigate the influence of vascular hypertrophy and insulin resistance on LV hypertrophy and its function in patients with hypertension. In 89 patients with essential hypertension and electrocardiographic LV hypertrophy, we measured blood pressure; insulin sensitivity by hyperinsulinaemic euglucaemic clamp; minimal forearm vascular resistance (MFVR) by plethysmography; intima-media cross-sectional area of the common carotid arteries (IMA) by ultrasound; and LV mass, relative wall thickness (RWT), systolic function and diastolic filling by echocardiography after two weeks of placebo treatment. LV mass index correlated to IMA/height (r=0.36, P=0.001), serum insulin (r=-0.25, P<0.05), plasma glucose (r=-0.34, P<0.01), and showed a tendency towards a correlation to insulin sensitivity (r=0.21, P=0.051), but was unrelated to MFVR. Deceleration time of early diastolic transmitral flow positively correlated to IMA/height (r=0.30, P<0.01). The ratio between early and atrial LV filling peak flow velocity negatively correlated to MFVR(men) (r=-0.30, P<0.05). Endocardial and midwall systolic LV function were not related to vascular hypertrophy, plasma glucose, serum insulin or insulin sensitivity. In conclusion, insulin resistance was not related to LV hypertrophy or reduced LV function. However, high thickness of the common carotid arteries was associated with LV hypertrophy and high deceleration time of early diastolic transmitral flow. High MFVR was associated with low ratio between early and atrial LV filling peak flow velocity. This may suggest that systemic vascular hypertrophy contributes to abnormal diastolic LV relaxation in patients with hypertension and electrocardiographic LV hypertrophy.

Smoking and relation to other risk factors in postmenopausal women with coronary artery disease, with particular reference to whole blood viscosity and beta-cell function.

OBJECTIVES: To investigate possible associations between smoking habits and other coronary risk factors in postmenopausal women with known coronary heart disease (CHD). SETTING: The study was conducted at a university clinic. SUBJECTS: A total of 118 postmenopausal women with CHD verified with angiography, consecutively recruited. INTERVENTIONS: Conventional treatment for CHD. The women were randomized to hormone replacement therapy (HRT) with transdermal 17-beta oestradiol and medroxyprogesterone acetate, or to a control group. RESULTS: Smokers were younger (P = 0.005), had lower body mass index (P = 0.04) and lipoprotein Lp(a) levels (P = 0.02) compared with nonsmokers. Smokers had reduced beta-cell function (homeostasis model assessment, P = 0.006), whereas whole blood viscosity (WBV) was higher at all shear rates. WBV was not affected by HRT over a 12-month period. Oestrone levels were higher in smokers. CONCLUSIONS: Smoking adversely affects insulin secretion (beta-cell function) and WBV in postmenopausal women with established CHD, which could be of importance as a mechanism for the increased risk of CHD in smokers. The importance of smoking as a risk factor, overrides the effect of Lp(a), which is lower in smokers compared with nonsmokers.

Glucose disposal rates calculated from 60- to 90-minute isoglycemic hyperinsulinemic glucose clamp correlate with cardiovascular risk factors in borderline hypertensive young men.

The hyperinsulinemic glucose clamp is generally performed for at least 120 minutes, due to assumptions of steady-state. We were interested in relationships between glucose disposal rate (GDR) and cardiovascular risk factors, rather than a standard measure of insulin sensitivity per se. Therefore, we analyzed 120-minute clamps performed on borderline hypertensive, but otherwise healthy young men (n = 19). GDR was calculated at different time points and related to baseline cardiovascular risk factors and responses to a mental stress test (MST). The 60-, 90-, and 120-minute GDR correlated significantly with serum high-density lipoprotein (HDL) cholesterol (r=.59, r=.50, and r=.53, respectively), heart rate (HR) during MST (r = -.65, r = -.64, and r = -.58, respectively) and plasma epinephrine (Epi) (r = -.55, r= -.58, and r = -.56, respectively) and norepinephrine (NE) (r = -.52, r = -.49, and r = -.48, respectively) 1 minute after announcement of the MST (all P <.05). Although not statistically significant at all time points, similar relationships were observed between GDR and resting HR, systolic blood pressure (BP) at rest and during mental stress, body mass index (BMI), serum total cholesterol (Chol), serum triglycerides (TG), and blood hemoglobin (HgB), with remarkable consistency from about 40 to 50 minutes onwards. HDL cholesterol and Epi remained independent in stepwise multiple regression analyses with the 60-, 90-, and 120-minute GDR as dependent variables (all P <.05). We suggest that 60- to 90-minute glucose clamps may provide information about the relationship between insulin sensitivity and various cardiovascular risk factors in borderline hypertensive young caucasian men.

Polymorphisms in candidate genes for blood pressure regulation in young men with normal or elevated screening blood pressure.

We have previously shown correlations between cardiovascular risk factors such as blood pressure (BP), sympathetic nervous system activity, lipids and insulin resistance in young men with elevated screening BP. In the present study we aimed to: (1) compare the genotype distribution and allele frequencies of 11 polymorphisms in seven candidate genes for BP regulation in healthy 21-year-old Caucasian men, between 18 men with normal and 67 men with high screening BP, and (2) evaluate the effect of these polymorphisms in candidate genes on casual BP, BP responses to mental stress or catecholamines and metabolic parameters including insulin sensitivity. There were no differences in genotype distributions or allele frequencies between the subjects with normal and those with high screening BP. Insulin sensitivity was significantly higher in GG homozygotes in the G-261A polymorphism at the alpha 2A-adrenergic receptor (alpha(2A)AR) locus compared to GA heterozygotes (p = 0.007). Subjects who were homozygous both GG in the G-261A polymorphism at the alpha(2A)AR locus and GlyGly in the Arg16Gly polymorphism at the beta2-adrenergic (beta2AR) receptor loci had significantly higher insulin sensitivity and lower catecholamine levels during mental stress than subjects with other genotypes. Subjects who were II homozygous at the angiotensin converting enzyme (ACE) locus and AA homozygous at the angiotensin type I receptor (AT1R) locus had lower BP and a better lipid profile than the rest of the group. Thus, in this explorative study, we report an association between insulin sensitivity and a polymorphism at the alpha(2A)AR locus. We suggest the presence of gene-gene interactions in the renin-angiotensin system and the sympathetic nervous system.

[Bilateral renal artery stenosis--a cause of acute pulmonary edema]. / Bilateral nyrearteriestenose--en årsak til akutt lungeødem.

BACKGROUND: Renal artery stenosis may present as acute pulmonary oedema and be misinterpreted as congestive heart failure. ACE inhibitors and angiotensin-II antagonists are widely used among patients with congestive heart failure and hypertension. MATERIAL AND METHODS: The authors present a patient with congestive heart failure caused by a combination of coronary heart disease and bilateral renal artery stenosis. The patient developed acute kidney failure secondary to ACE inhibitor and angiotensin II antagonist treatment. RESULTS: Mechanisms behind pulmonary oedema secondary to renovascular hypertension are discussed. INTERPRETATION: Revascularisation is the treatment of choice for this patient category.

Biphasic effect of epinephrine on blood glucose during hyperinsulinemia in borderline hypertensive young men.

We aimed to study the glycemic response to epinephrine during hyperinsulinemia and infused epinephrine (0.03 microg/kg/min) for 30 min after 90 min of hyperinsulinemic glucose clamp in 14 borderline hypertensive young men. Plasma epinephrine was increased from 0.34 +/- 0.08 to 2.33 +/- 0.33 nmol/L while insulin and glucose infusions were kept constant with consequent changes in blood glucose. Initially (90 to 95 min), there was a decrease in blood glucose (P = .016) that correlated negatively with glucose disposal rate corrected for insulin (r = -0.55, P = .040) and positively with fasting insulin (r = 0.55). Thereafter, there was an increase in blood glucose (95 to 120 min) (P < .001) that persisted during the recovery period (120 to 140 min). The glucose increase (90 to 140 min) correlated positively with fasting insulin (r = 0.55), systolic blood pressure (r = 0.57), delta epinephrine 90 to 120 min (r = 0.59), and baseline epinephrine (r = 0.57). Blood glucose remained unchanged (P = .207) in a saline control group (n = 6) with a significant group X treatment effect versus epinephrine (P = .003). Thus, epinephrine caused a biphasic response in blood glucose during hyperinsulinemia. The initial dip in glucose was more pronounced with higher insulin sensitivity, corresponding to previous observations during mental stress test. The following increment in blood glucose was positively related to insulin, systolic blood pressure, and epinephrine levels. These data suggest that insulin may modify the glycemic response to epinephrine in a potentially favorable direction and indicate some lag time before epinephrine gains effect. Subjects who are insulin sensitive and have low blood pressure and resting epinephrine levels seem to be less prone to hyperglycemia induced by epinephrine.

Gender specific sympathetic and hemorrheological responses to mental stress in healthy young subjects.

OBJECTIVE: Activation of the sympathetic nervous system may increase hematocrit (Hct), whole blood viscosity (WBV), and possibly cardiovascular risk. The aim was to study gender specific differences of mental stress on sympathetic reactivity and blood rheology. METHODS: Responses in blood pressure, heart rate (HR), Hct, WBV (Bohlin rotational viscosimeter), and plasma catecholamines to a mental arithmetic stress test (MST) were measured in male (n = 10, 23 +/- 3 years, BMI 23 +/- 2 kg/m2) and female (n = 10, 21 +/- 4 years, BMI 24 +/- 2 kg/m2) students. RESULTS: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR increased during MST in men and women, and declined to baseline levels after 15 min of recovery. In men, plasma adrenaline increased by 217% during MST (p < 0.01, ANOVA). and plasma noradrenaline increased by 68% (p < 0.05). Hct and WBV at low shear rates (0.5 and 1.1 l/s) increased as well (p < 0.001, p < 0.05, and p < 0.05, respectively). In women, the increase in plasma adrenaline averaged 118% during MST (p < 0.05) while plasma noradrenaline (-3%, p = 0.38), Hct, and WBV at all shear rates remained unchanged. Men and women differed in A adrenaline (p < 0.05), A noradrenaline (p = 0.01), delta Hct (p < 0.05), and delta WBV (p < 0.05). A Hct tended to correlate with delta SBP (r= 0.60, p = 0.07), A DBP (r = 0.57. p = 0.09). and delta HR (r = 0.50, p = 0.14), and correlated significantly with A noradrenaline (r = 0.66, p < 0.05) in men only. Multiple regression analysis showed that gender independently explained 22% of the change in Hct during mental stress. CONCLUSION: Data suggest gender specific differences in sympathetic and hemorrheological responses to mental stress in healthy young subjects. In men, sympathetic responses were related to hemorrheological responses, but not in women. It may be speculated whether such differences in stress responses may contribute to lower cardiovascular risk in premenopausal women than in men.

Blood viscosity, plasma adrenaline and fasting insulin in hypertensive patients with left ventricular hypertrophy. ICARUS, a LIFE Substudy. Insulin CARotids US Scandinavica.

We have seen relationships between whole blood viscosity (WBV) and components of the metabolic cardiovascular syndrome in borderline hypertensive young men and suggested that sympathetic nervous system (SNS) activity may be a mediator. In the present study we aimed to test this hypothesis in established hypertension and to investigate the relationship between WBV and cardiac dimensions. Unmedicated patients (n = 42) with stage II-III hypertension and electrocardiographic left ventricular hypertrophy (LVH) underwent hyperinsulinemic isoglycemic glucose clamp to assess glucose disposal rate (GDR) and echocardiographic studies. WBV, plasma catecholamines and insulin were measured in arterialized venous blood. WBV at high shear rate correlated with baseline plasma adrenaline (r = 0.33, p = 0.04) and fasting insulin (r = 0.34, p = 0.04) while there was a negative trend for GDR (r = -0.21, p = 0.2). WBV at low shear rate correlated with plasma adrenaline (r = 0.49, p = 0.002) and resting heart rate (r = 0.36, p = 0.02). WBV was higher in smokers than in non-smokers (p = 0.02) and in males than in females (p = 0.02). Fasting insulin independently explained 12% of the variation in WBV at high shear, while baseline adrenaline independently explained 17% of the variation in WBV at low shear. Systolic blood pressure explained 31% of the variation in LV mass index. Thus, we demonstrate positive relationships between blood viscosity versus plasma adrenaline and fasting insulin in hypertensive patients with LVH. We suggest that adrenergic activity may increase hematocrit and viscosity and hence reduce insulin sensitivity.

Assessment of insulin sensitivity by 90 min isoglycaemic hyperinsulinaemic glucose clamp in healthy young men.

We aimed to perform a detailed analysis of the isoglycaemic hyperinsulinaemic glucose clamp in relation to the time spent in performing the procedure, and analysed two series performed by independent investigators on different groups (n = 19 and n = 28) of healthy, young men. We calculated glucose disposal rates (GDR) during 20-min periods at different time points during the clamp. There was no difference in 90- and 120-min GDR when comparing the two series. The differences between 90- and 120-min GDR were (mean +/- SD) 0.48 +/- 1.10 mg/kg/min (p = 0.73) and 0.37 +/- 1.05 mg/kg/min (p = 0.71), respectively. The correlations between 90- and 120-min GDR were 0.94 (p < 0.001) and 0.89 (p < 0.001). Correlations between GDR during the second hour of the clamp and fasting plasma insulin ranged from -0.53 (p = 0.020) to -0.55 (p = 0.016) and from -0.44 (p = 0.020) to -0.54 (p = 0.003), respectively, and did not improve after 60 min of clamping. These data suggest that reliable indices of insulin sensitivity in healthy young men may appear even when the isoglycaemic hyperinsulinaemic clamp procedure is shortened from 120 to 90 min. A shorter procedure is time-effective and less expensive, but may be limited to healthy, young Caucasian men.

Effects of hyperinsulinemia on sympathetic responses to mental stress.

In a recent study, we could not find evidence to support the hypothesis that insulin activates the sympathetic nervous system (SNS) during a hyperinsulinemic glucose clamp procedure. Mental stress tests (MST), however, may be used to detect differences in blood pressure and SNS activity that are not present during baseline or resting conditions. In this study, we aimed to investigate the effects of hyperinsulinemia during glucose clamp on blood pressure and sympathetic responses to mental stress. Borderline hypertensive but otherwise healthy 21-year-old men (n = 18) underwent 5 min of mental arithmetic stress testing (MST-1) before and at the end of 120 min of isoglycemic hyperinsulinemic glucose clamp (MST-2) with infusion rates of glucose and insulin kept constant. Insulin concentration increased from 119 +/- 10 pmol/L to 752 +/- 65 pmol/L. We observed highly significant increases in blood pressure and heart rate in response to MST, but neither insulin nor saline solution infusions affected these responses. During MST-1, norepinephrine increased by 461 +/-165 pmol/L (mean +/- SEM) and epinephrine by 218 +/- 76 pmol/L. During MST-2 the changes were 372 +/- 112 pmol/L and 187 +/- 60 pmol/L, respectively. The norepinephrine (P = .8) and epinephrine (P = .7) responses were unchanged by insulin. Thus, there were similar increases in blood pressure, heart rate, and plasma catecholamine concentrations in arterialized venous blood in response to MST despite the infusion of insulin. A possible time effect was excluded by including a saline solution control group (n = 7) that showed almost identical results. Our results suggest that acute hyperinsulinemia during isoglycemic glucose clamp does not interfere with cardiovascular or sympathetic responses to mental stress.

Relative influence of insulin resistance versus blood pressure on vascular changes in longstanding hypertension. ICARUS, a LIFE sub study. Insulin Carotids US Scandinavia.

BACKGROUND: Insulin resistance is associated with hypertension. The relative influences of hyperinsulinaemia and high blood pressure on vascular hypertrophy and carotid distensibility is unclear in patients with longstanding hypertension. METHODS: In 88 unmedicated patients with stage II-III hypertension and left ventricular hypertrophy on electrocardiogram we measured blood pressure, minimal forearm vascular resistance (MFVR) using plethysmography, intima-media thickness (IMT) and the wall distensibility of the common carotid arteries using ultrasound, and insulin sensitivity using a 2-h isoglycaemic hyperinsulinaemic clamp. RESULTS: IMT was positively correlated to systolic blood pressure (r= 0.26, P < 0.05), whole body glucose uptake index (M/IG; r= 0.22, P< 0.05), age (r= 0.24, P< 0.05) and negatively correlated to body mass index (r= -0.24, P < 0.05); IMT did not correlate to fasting serum insulin (r= -0.14, NS). In men (n = 64) MFVR was positively correlated to systolic blood pressure (r = 0.30, P < 0.05), but was unrelated to M/G and serum insulin. The distensibility of the common carotid arteries was negatively correlated to systolic blood pressure (r = -0.40, P< 0.001) and in untreated patients (n = 22) positively correlated to M/IG (r = 0.47, P < 0.05). CONCLUSIONS: High systolic blood pressure was related to vascular hypertrophy, whereas hyperinsulinaemia and insulin resistance were not, suggesting that longstanding high blood pressure is a far more important determinant for structural vascular changes than insulin resistance at this stage of the hypertensive disease. However, hyperinsulinaemia and insulin resistance were associated with low distensibility of the common carotid arteries in the subgroup of never treated hypertensive patients.

Insulin sensitivity is related to physical fitness and exercise blood pressure to structural vascular properties in young men.

Insulin resistance is related to physical inactivity, which is a risk factor for cardiovascular disease and death. Moreover, blood pressure responses during the first 6 minutes of an exercise test (600 kilo/pound/meter [kpm] per min) are more predictive for cardiovascular morbidity and mortality than blood pressure at rest, which could reflect that exercise blood pressure correlates more closely to peripheral structural vascular changes than casual blood pressure. We have recently shown a correlation between insulin resistance and minimal forearm vascular resistance (MFVR) in young men recruited from the highest blood pressure percentiles during a military draft session. In the present study, we tested the hypotheses that insulin sensitivity relates to physical fitness and that blood pressure responses during an exercise test relate to peripheral structural vascular changes in these men; we also tested whether these findings were interrelated. We assessed insulin sensitivity and physical fitness in 27 young men randomly selected from the cohort having a blood pressure of 140/90 mm Hg or higher during the compulsory military draft session in Oslo. Insulin sensitivity correlated with physical fitness (r=0.58, P=0.002). Systolic blood pressure after 6 minutes of exercise (600 kpm/min) correlated with MFVR (r=0.46, P=0.015). MFVR and physical fitness independently explained 60% of the variation in insulin sensitivity, and MFVR independently explained 19% of the variation of systolic blood pressure after 6 minutes of exercise. In conclusion, insulin sensitivity is related to physical fitness and exercise blood pressure to structural vascular properties in these young men.

Increased forearm blood flow during glucose clamp is related neither to insulin sensitivity nor to hyperinsulinemia in borderline hypertensive young men.

It is controversial whether raised insulin within the physiological concentration range increases forearm blood flow (FBF). The aim of the present study was therefore to examine the effect of the isoglycemic hyperinsulinemic glucose clamp procedure on FBF and to relate the increase to the glucose disposal rate (GDR), i.e. insulin sensitivity. Borderline hypertensive young men were examined with the clamp technique or received saline infusion, and FBF was measured using plethysmography. It is of particular interest to study this group of subjects because their GDR correlates to a number of metabolic and hemodynamic variables, and these subjects hyperreact to stressful stimuli. There was no correlation between deltaFBF during clamp and GDR (r = -0.002, p = 0.99, n = 28). While serum insulin increased from 107 +/- 5 to 628 +/- 31 pmol/l in the hyperinsulinemic group and remained unchanged (135 +/- 11 vs 116 +/- 11 pmol/l) in the saline group, FBF increased from 3.5 +/- 0.3 to a maximum of 5.1 +/- 0.4 ml/min/100 ml (p < 0.001, n = 28) and from 2.8 +/- 0.5 to a maximum of 4.5 +/- 0.5 ml/min/100 ml (p = 0.01, n = 8), respectively. The increase in FBF (delta%) was similar in the two groups (p = 0.9). Thus, we could not demonstrate any relationship between insulin sensitivity and increments in FBF during hyperinsulinemic glucose clamp in borderline hypertensive young men. The moderate increases in FBF during insulin infusion with serum concentrations within the physiological range seem to be time-dependent and not caused by hyperinsulinemia.

Relationship between insulin sensitivity and maximal forearm blood flow in young men.

Insulin resistance is a part of the metabolic cardiovascular syndrome. We aimed to test the hemodynamic hypothesis of insulin resistance, which suggests that a decreased skeletal muscle blood supply with subsequent reduced nutritional flow causes insulin resistance in skeletal muscle. We assessed determinants of peripheral blood flow such as maximal forearm blood flow (MFBF), minimal forearm vascular resistance (MFVR), and whole blood viscosity (WBV) in 27 young men with borderline elevation of blood pressure. Insulin sensitivity measured as glucose disposal rate (GDR) correlated with MFBF (r=0.55, P=0.003), MFVR (r=-0.58, P=0. 002), and WBV (r=-0.39, P=0.046 at shear rate 201 s-1). There was no correlation between GDR and myocardial thickness or left ventricular mass. In a stepwise multiple regression analysis, MFVR and WBV explained 54% of the variation in GDR. The relative increase in mean arterial blood pressure during a mental stress test, as a marker of reactivity or an alert reaction, was correlated with MFVR (r=0.56, P=0.002) and inversely with GDR (r=-0.45, P=0.018) and MFBF (r=-0.49, P=0.01) but not with cardiac dimensions. In a stepwise multiple regression analysis, 48% of the increase in blood pressure during a mental stress test was explained by MFVR and WBV. Fasting insulin correlated with MFVR (r=0.41, P=0.036) and GDR (r=-0.62, P=0.001). These data show a positive association between the appearance of peripheral structural vascular changes as quantified through a hemodynamic technique and insulin resistance in young men with borderline elevation of blood pressure. The cause-effect relationship of this finding needs further evaluations.

Whole-blood viscosity and the insulin-resistance syndrome.

BACKGROUND: In a previous study we found that elevated blood viscosity was linked to the insulin resistance syndrome, and we proposed that high blood viscosity may increase insulin resistance. That study was based on calculated viscosity. OBJECTIVE: To determine whether directly measured whole-blood viscosity was related to the insulin-resistance syndrome in the same way as calculated viscosity had been found to be. METHODS: Healthy young men were examined with the hyperinsulinemic isoglycemic glucose clamp technique, and we related insulin sensitivity (glucose disposal rate) to other metabolic parameters and to blood viscosity. We established a technique for direct measurement of whole-blood viscosity. RESULTS: There were statistically significant negative correlations between glucose disposal rate and whole-blood viscosity at low and high shear rates (r = -0.41, P = 0.007 for both, n = 42). Whole-blood viscosity was correlated positively (n = 15) to serum triglyceride (r = 0.54, P = 0.04) and total cholesterol (r = 0.52, P = 0.05), and negatively with high-density lipoprotein cholesterol (r = -0.53, P = 0.04) concentrations. Insulin sensitivity index was correlated positively to high-density lipoprotein cholesterol (r = 0.54, P = 0.04) and negatively to serum triglyceride (r = -0.69, P = 0.005) and to total cholesterol (r = -0.81, P = 0.0003) concentrations. CONCLUSIONS: The present results demonstrate for the first time that there is a negative relationship between directly measured whole-blood viscosity and insulin sensitivity as a part of the insulin-resistance syndrome. Whole-blood viscosity contributes to the total peripheral resistance, and these results support the hypothesis that insulin resistance has a hemodynamic basis.

Insulin modifies the glucose response to mental stress independently of forearm blood flow.

In the present study we aimed to reproduce and extend our recent finding that insulin infusion modifies the glucose response to mental stress and to determine whether the altered glucose response, i.e. glucose uptake, may be explained by a rise in forearm blood flow (FBF). The subjects were borderline hypertensive; there was one former blood pressure measurement > or =140/90 mm Hg, but otherwise they were healthy 21-year-old men. In the first series (n = 18) the subjects were exposed to a 5-min mental arithmetic stress test prior to (MST-1) and at the end of (MST-2) 120 min of hyperinsulinemic glucose clamp. Blood glucose was unchanged (0.067+/-0.05 mmol/l, p = 0.24) during MST-1 and decreased (-0.37+/-0.09 mmol/l, p = 0.001) during MST-2. Blood glucose also decreased in a second series (n = 28) in which the subjects were exposed to MST after 120 min of glucose clamp (-0.33+/-0.09 mmol/l , p = 0.001), and FBF increased from 4.4+/-0.4 to 7.7+/-1.1 ml/min/100 ml (p<0.0001). Glucose was unchanged (p = 0.48) in response to MST in a saline time control group (n = 8). However, FBF increased in response to MST from 3.7+/-0.5 to 7.0+/-1.2 ml/min/100 ml (p<0.01). The increase in FBF averaged 3.3 ml/min/100 ml in both groups. Serum insulin remained unchanged in response to MST in controls, but decreased in response to MST during insulin infusion in both series (p = 0.04 and p = 0.004, respectively). The fall in glucose in response to MST during insulin infusion correlated with glucose disposal rate (GDR) (r = -0.40, p = 0.034, n = 28) and inversely with fasting insulin (r = 0.52, p = 0.004, n = 28). Thus, insulin infusion alters the glucose response to mental stress, i.e. there is a decrease in blood glucose concentration concomitant with an increased uptake. This glucose uptake is unrelated to FBF, but related to higher skeletal muscle insulin sensitivity and inversely to the fasting insulin level. Our data therefore suggest that infused insulin modifies the stress response through a mechanism at the tissue level. It may be speculated whether insulin counteracts unfavourable effects of mental stress and sympathetic activation on glucose metabolism.