Differences in insulin sensitivity and risk markers due to gender and age in hypertensives.

Men run a higher risk for cardiovascular disease than women, even if hypertensive. This has been attributed to a more pronounced central (abdominal) fat distribution in men as well as menopausal state in women. The hypothesis to be tested in hypertensives was that men have more pronounced insulin resistance and other cardiovascular risk factors than pre-menopausal, but not post-menopausal, women.

Effects of hydrochlorothiazide and captopril on lipoprotein lipid composition in patients with essential hypertension.

Objective: Effective antihypertensive agents may differ in their capacity to reduce cardiovascular risk because they induce potentially atherogenic alterations in lipoprotein composition.

Patients: To assess this possibility, the effects of five months' treatment with either hydrochlorothiazide (HCTZ) or the converting enzyme inhibitor captopril (CAPT) on lipoprotein lipid composition were compared in thirty normolipidaemic patients with essential hypertension (EH).

Results: The sixteen patients treated with HCTZ showed the expected directional alterations in plasma TG (+31%), HDL2-C (-16%), and CHOL (+7.

Abnormal lipoprotein phospholipid composition in patients with essential hypertension.

Vascular cell membranes from patients with essential hypertension (EH) and animals with genetic forms of hypertension have been found to have alterations in the content of free cholesterol and negatively charged phospholipids that may modify their function. Since membrane and lipoprotein lipids exchange freely, the lipid composition of lipoproteins may be an indirect measure of the content of vascular and other cells. To determine whether abnormalities are present in the lipid and phospholipid composition of lipoproteins from patients with EH, 30 EH (11 women; 19 men) and 20 normotensive control subjects were studied.

Increased level of hemoglobin A1c, but not impaired insulin sensitivity, found in hypertensive and normotensive smokers.

Smoking is associated with an abnormal plasma lipoprotein pattern. Recently, both insulin resistance and normal insulin action have been reported in smokers. In a total of 191 hypertensive and normotensive subjects recruited from a health survey, serum lipoprotein lipids, glucose tolerance (by intravenous glucose tolerance test (IVGTT), insulin secretion, and insulin sensitivity (euglycemic insulin clamp) were compared in the 41 smokers and 150 nonsmokers.

Metabolic effects of anti-hypertensive treatment with nifedipine or furosemide: a double-blind, cross-over study.

To evaluate the metabolic effects of two anti-hypertensive agents with different actions, nifedipine 20 mg twice daily and furosemide 60 mg twice daily, 23 patients with untreated essential hypertension performed a double-blind, cross-over study in treatment periods of 5 months. Metabolic effects were evaluated by serum lipoprotein determinations, the intravenous glucose tolerance test and the hyperinsulinaemic euglycaemic clamp technique. Nifedipine and furosemide reduced blood pressure to the same extent (-14 to -15 mm Hg for supine SBP and -9 to -10 mm Hg for supine DBP, both P < 0.

Long-term metabolic effects of antihypertensive drugs.

In short-term studies (4 to 6 months) we have reported that antihypertensive treatment with beta-adrenergic blockade and thiazide diuretics induced insulin resistance, hyperinsulinemia, and a deranged lipid profile; the ACE inhibitor captopril increased insulin sensitivity without affecting serum lipids. In the present study, 65 of the original 149 patients with essential hypertension included in the short-term studies were reexamined after treatment for 2 to 3 years. The hyperinsulinemic euglycemic clamp method showed that the significant decrease in insulin sensitivity (p < 0.

Metabolic effects of isradipine as monotherapy or in combination with pindolol during long-term antihypertensive treatment.

Objectives: To evaluate the effects of isradipine alone and in combination with pindolol on glucose and lipid metabolism during long-term antihypertensive therapy.

Design: Open long-term study with parallel groups.

Setting: Kungsgärdet Geriatric Hospital, Uppsala, a tertiary referral hospital.

On the interplay between insulin secretion and sensitivity as determinants of glucose tolerance.

Both insulin secretion and sensitivity have been claimed to be the main characteristics in the determination of future deterioration in glucose tolerance. In this cross-sectional study insulin secretion and insulin sensiturity were determined in 228 subjects with varying degrees of glucose tolerance. Insulin secretion was measured in an intravenous glucose tolerance test (IVGTT) and insulin sensitivity by the hyperinsulinaemic euglycaemic clamp test.

Influences of different antihypertensive treatments on indices of systemic mineral metabolism.

A negative calcium balance has previously been described in human hypertension with low levels of plasma ionized calcium (Ca2+) and an increased urinary excretion of calcium. The cause of this disturbance in mineral metabolism is not known, nor is it known if this derangement could be abolished if blood pressure is reduced by antihypertensive treatment. In the present investigation, the effects of antihypertensive monotherapy on serum and fasting urinary electrolytes were studied.

Is it hyperinsulinemia or insulin resistance that is related to hypertension and other metabolic cardiovascular risk factors?

Aim Of Study: Epidemiologic and clinical studies have shown a close association between hypertension, hyperlipidemia and glucose intolerance. A metabolic imbalance has been proposed. As both hyperinsulinemia and insulin resistance appear to be of pathogenetic importance in this metabolic syndrome, we studied these features in hypertensive and normotensive subjects.

On the relationships between mineral metabolism, obesity and fat distribution.

Alterations in calcium metabolism have been associated with cardiovascular risk factors. An altered binding of calcium to plasma proteins and raised levels of parathyroid hormone (PTH) have been described in morbid obesity. In the present study, indices of mineral metabolism were related to obesity (body mass index, BMI) and fat distribution (waist to hip ratio, w/h) in 194 subjects with a wide range of BMI and w/h.

Calcium metabolism and sodium sensitivity in hypertensive subjects.

A pattern of negative calcium balanced with lowered levels of serum ionized calcium (Ca2+) and increased urinary excretion of calcium has been reported in hypertensive men. In the present study, ten untreated hypertensive subjects were salt loaded (20 g NaCl) for one week after a week on a low salt diet (< 3 g). The change in mean blood pressure (MBP) at the end of the high compared with the low salt diet was called salt sensitivity and was related to indexes of mineral metabolism.

Supplementation with n-3 fatty acids reduces triglycerides but increases PAI-1 in non-insulin-dependent diabetes mellitus.

The effects of dietary supplementation with n-3 fatty acids on lipid and glucose metabolism and on fibrinolysis were evaluated in 14 non-insulin-dependent diabetic patients who were given 10 g of MaxEPA (3 g n-3 fatty acids) or placebo (olive oil) per day in a randomized double-blind cross-over study during two consecutive 8-week periods. The serum triglyceride (TG) concentrations decreased by 27% (P < 0.01) after addition of MaxEPA with a reduction of VLDL TG by 36% (P < 0.

Fasting insulin, calcium metabolism and the electrocardiogram in hypertensive subjects.

Changes in both calcium and insulin metabolism have been described in essential hypertension. Low levels of plasma ionized calcium (Ca2+) and high levels of insulin have previously been associated with vascular complications and coronary heart disease. In the present study, indices of calcium metabolism and fasting serum insulin were related to electrocardiographic (ECG) variables in 58 patients with untreated hypertension.

The sympathetic response to euglycaemic hyperinsulinaemia. Evidence from microelectrode nerve recordings in healthy subjects.

Sympathetic nervous system activation by insulin has been suggested as a mechanism explaining the association between insulin resistance and hypertension. We further examined the effect of insulin by direct microneurographic muscle and skin nerve sympathetic activity recordings during euglycaemic insulin clamps in healthy subjects. The mean plasma insulin level was elevated from 5.

Metabolic cardiovascular risk factors and sodium sensitivity in hypertensive subjects.

Hypertension has previously been suggested to be a part of a metabolic syndrome also involving hyperlipidemia, hyperinsulinemia, and decreased insulin sensitivity. In the present study, 10 untreated hypertensive subjects were challenged with a high-salt diet (20 g NaCl) for 1 week after 7 days on a low-salt diet (less than 3 g). The difference in mean blood pressure (MBP) at the end of the high-salt diet v the low-salt diet was denoted salt sensitivity.

Metabolic effects of pindolol and propranolol in a double-blind cross-over study in hypertensive patients.

Metabolic effects of pindolol and propranolol were investigated in a randomised study of double-blind, double-dummy design in 39 Caucasians with newly detected hypertension. Each active treatment period was 6 months long. A euglycaemic hyperinsulinaemic clamp test was done to measure insulin sensitivity, and i.

The metabolic and circulatory response to beta-blockade in hypertensive men is correlated to muscle capillary density.

Both haemodynamic and metabolic variables have been shown to be related to the fibre composition and capillary density of skeletal muscle in man. In the present study, the change of several metabolic variables during beta-blockade was investigated and related to muscle fibre composition and capillary density in 28 men with essential hypertension. They had been given atenolol (50 mg/day) or metoprolol (200 mg/day) or propranolol (160 mg/day) for 4-12 months.

Effects of antihypertensive treatment on insulin sensitivity with special reference to ACE inhibitors.

In 1984, the suspicion that pharmacological treatment may worsen the insulin resistance and associated metabolic abnormalities in lipid and carbohydrate metabolism and contribute to the relative failure of antihypertensive treatment to produce more than marginal reductions in cardiovascular morbidity and mortality led us to start a series of trials aimed at elucidating how antihypertensive drugs affect insulin sensitivity. These trials, which included assessment of insulin sensitivity by the euglycemic insulin clamp, showed that beta-adrenergic blockade and thiazide diuretic treatment (hydrochlorothiazide) increase insulin resistance and basal plasma insulin, whereas Ca(2+)-channel antagonists (verapamil and diltiazem), with the exception of the negative effect of nifedipine, are metabolically neutral. alpha-Adrenergic blockade with prazosin and angiotensin-converting enzyme (ACE) inhibition with captopril enhance insulin sensitivity.

Lipoprotein lipase activity in skeletal muscle is related to insulin sensitivity.

The relative effects of obesity, alone or in combination with insulin resistance and hyperinsulinemia (with or without diabetes), on lipoprotein concentrations, blood pressure, and other risk factors for cardiovascular disease were investigated in 28 men (mean age, 63 years). Special attention was given to lipoprotein lipase (LPL) activity in tissues and to postheparin plasma LPL activity and hepatic lipase activity and their relation to insulin resistance. The 28 men fulfilled the entrance criteria of the study so that they could be allocated to one of the four groups (seven in each group): 1) normal body weight, normal fasting insulin level, and normal glucose tolerance (controls); 2) the same as in group 1 but with moderate obesity; 3) the same as in group 2 but with fasting hyperinsulinemia; 4) the same as in group 3 but with non-insulin-dependent diabetes mellitus.

Blood pressure response during long-term treatment with magnesium is dependent on magnesium status. A double-blind, placebo-controlled study in essential hypertension and in subjects with high-normal blood pressure.

Both experimental and epidemiological studies support the idea of magnesium supplementation in essential hypertension. We added 15 mmol Mg to a free diet in 71 subjects with mild essential hypertension or a high-normal blood pressure in a double-blind, placebo-controlled study over 6 months. The treatment, which raised urinary magnesium excretion 30%, induced no general effects on the blood pressure.

Different aetiologies of type 2 (non-insulin-dependent) diabetes mellitus in obese and non-obese subjects.

Insulin responses to intravenous glucose infusion and glucose utilization during hyperinsulinaemic euglycaemic clamp were determined in a large homogeneous group of 65-year-old male subjects. Twenty-eight had untreated Type 2 (non-insulin-dependent) diabetes mellitus and the remaining 44 control subjects had a normal glucose tolerance. Diabetic patients with abdominal obesity displayed peripheral insulin resistance in combination with defective insulin secretion, whereas non-obese diabetic patients showed only a secretory defect.

Screening for insulin receptor gene DNA polymorphisms associated with glucose intolerance in a Scandinavian population.

The significance of insulin receptor gene variants in the aetiology of Type 2 (non-insulin-dependent) diabetes mellitus has been investigated by analysis of restriction fragment length polymorphisms in a genetically homogeneous Swedish population. Seven polymorphisms were analysed, spanning functionally important regions of the insulin receptor locus. Four of these polymorphisms were mapped more accurately within the gene compared to previous studies.

Potassium and blood pressure.

The relationships between serum potassium and urinary excretion of potassium and blood pressure were determined in an unmedicated adult population with a wide range of blood pressure (mean arterial blood pressure 100-130 mm Hg, n = 71). Inverse correlations between both serum potassium concentration and urinary excretion of potassium and standing (but not supine) mean blood pressure were seen (r = -0.41, p less than 0.

Insulin sensitivity and blood lipids during antihypertensive treatment with special reference to ACE inhibition.

NIDDM and hypertension are both characterized by insulin resistance and/or hyperinsulinemia. In IDDM, factors associated with nephropathy produce hypertension. To avoid exacerbation of the metabolic condition, and to prevent further deterioration in glycemic control, treatment of hypertension in the diabetic patient should include the administration of medication with the fewest adverse effects on glucose homeostasis.