Biomedical subjects

H Lithell

Publications and source records attributed to H Lithell.

At least 127 records · Page 7Linked to original sources

PubMed1994

Metabolic effects of long-term angiotensin-converting enzyme inhibition with fosinopril in patients with essential hypertension: relationship to angiotensin-converting enzyme inhibition.

Fifty patients with mild to moderate essential hypertension were randomized to receive either 20 mg fosinopril daily for 16 weeks or placebo for 4 weeks followed by 12 weeks of 50 mg atenolol daily. Prior to these 16 weeks there was a placebo wash-out period of 2-6 weeks. Blood pressure measurements, euglycaemic, hyperinsulinaemic glucose clamps, and intravenous glucose tolerance tests (IVGTT) were performed at baseline and after 4 and 16 weeks. Blood lipid status was evaluated at baseline and 16 weeks. The insulin sensitivity index (M/I) increased by 12% during the prolonged placebo period, and subsequently decreased by 12% during treatment with atenolol in that group. A post-hoc analysis of covariance indicated that the increase in insulin sensitivity during the initial 4 weeks may have been due to carry-over effects from previous antihypertensive treatment. Fosinopril increased glucose disappearance during IVGTT at 4 and 16 weeks (k values 1.46 and 1.33 vs 1.10 at baseline) but had no effect on insulin sensitivity. The change in insulin sensitivity and serum triglycerides during treatment with fosinopril was related to angiotensin-converting enzyme inhibition in serum. In conclusion, carry-over effects from previous antihypertensive medication were indicated in this study, probably because of an insufficient wash-out period in many patients. Therefore, 4 weeks of placebo wash-out in all patients is advisable in this kind of investigation.

Adolescent↗

PubMed1994

Insulin sensitivity is related to the fatty acid composition of serum lipids and skeletal muscle phospholipids in 70-year-old men.

Recent data indicate that peripheral insulin sensitivity may be influenced by dietary fat quality and skeletal muscle phospholipid fatty acid composition. During a health survey of 70-year-old men insulin sensitivity was measured by the euglycaemic hyperinsulinaemic clamp technique and the fatty acid composition of the serum cholesterol esters was determined (n = 215) by gas liquid chromatography. In a subsample the fatty acids of the skeletal muscle phospholipids and triglycerides were determined after fine needle biopsy from m. vastus lateralis (n = 39). The peripheral insulin sensitivity was significantly and negatively correlated to the proportion of palmitic (r = -0.31, p < 0.001), palmitoleic (r = -0.25, p < 0.001) and di-homo-gamma-linolenic (r = -0.33, p < 0.001) acids and positively to the content of linoleic (r = 0.28, p < 0.001) acid in the serum cholesterol esters. There was an even stronger negative relationship to the proportion of palmitic acid in the skeletal muscle phospholipds (r = -0.45, p < 0.004). The fatty acid composition was also significantly related to insulin sensitivity in a stepwise multiple regression analysis in the presence of other clinical variables, which were associated with insulin action in univariate analysis. Thus, more than 51% of the variation of the insulin sensitivity was explained by an equation containing body mass index, serum triglyceride concentration and the content of palmitic acid in the skeletal muscle phospholipids. It is concluded that the fatty acid composition in serum and of the phospholipids of skeletal muscle may influence insulin action in elderly men.

Aged↗

PubMed1994

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. Both the early insulin response in the IVGTT (increment) and the glucose disposal rate in the clamp test (M-value) were found to be related hyperbolically to fasting glucose (r = -0.63 and -0.66, respectively; both P < 0.0001) and in a second-order polynomial manner to the glucose disappearance rate (k-value) in the IVGTT (r = 0.53 and 0.48, respectively; both P < 0.0001). Multiple regression analysis showed the insulin increment in the IVGTT and the M-value in the clamp test to be equally important determinants of glucose tolerance, together explaining about 50% of the variation in fasting glucose and the k-value in the IVGTT. In conclusion, in this cross-sectional study insulin secretion and sensitivity studied over a broad range of glucose tolerance were found to be of almost equal importance in the determination of glucose tolerance. However, low levels of insulin increment in the IVGTT were more often associated with glucose intolerance than was a low insulin sensitivity.

Aged↗

PubMed1994

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 < 0.01) induced by treatment with pindolol, propanolol, metoprolol, atenolol, or hydrochlorothiazide after 4 to 6 months persisted after 2 to 3 years of treatment. Furthermore, the increase in insulin sensitivity reported for captopril after 6 months (p < 0.05) was not significantly altered during long-term treatment. Also, the raised levels of very low-density lipoprotein triglycerides (p < 0.01) and reduced levels of high-density lipoprotein cholesterol (p < 0.01) induced by most of the beta-adrenergic blockade without intrinsic sympathomimetic activity and hydrochlorothiazide persisted. Captopril, on the other hand, did not significantly affect the lipids during prolonged treatment. In conclusion, the magnitude of the metabolic effects induced by antihypertensive treatment during short-term studies was of the same order after long-term treatment over 2 to 3 years and were not significantly different from the results in the short-term studies.

Adrenergic beta-Antagonists↗

PubMed1994

Treatment with a beta-blocker with beta 2-agonism improves glucose and lipid metabolism in essential hypertension.

In a randomized double-blind crossover study in 42 patients with essential hypertension, the metabolic effects of a beta-adrenergic blocker with a pronounced beta 2-agonistic effect, dilevalol 400 mg x 1, were compared with those of metoprolol succinate 200 mg x 1. The effects of glucose metabolism were evaluated by the hyperinsulinemic euglycemic clamp technique and an intravenous glucose tolerance test (IVGTT). Insulin-mediated glucose disposal (M) and the insulin sensitivity index (M/I) increased by 19% (P = .011) and 10% (P = .27), respectively, during dilevalol treatment, but decreased by 10% (P = .15) and 22% (P = .0025), respectively, during metoprolol treatment, giving rise to significant differences between the two treatment regimens. Compared with dilevalol-treated patients, those treated with metoprolol showed increased plasma insulin values at the end of the IVGTT, but there was no difference in plasma glucose concentrations or glucose tolerance. Hemoglobin A1c (HbA1c) levels increased by 5.4% (P = .04) in the metoprolol group. Serum cholesterol, total serum and very-low-density lipoprotein (VLDL) triglycerides, and serum urate levels decreased significantly (by 6%, 22%, 29%, and 14%, respectively) during dilevalol treatment, and there was a significant difference between the effects of the two drugs on total, VLDL, and low-density lipoprotein (LDL) triglyceride and serum urate levels. These data demonstrate that a beta-blocker with a partial beta 2-agonist action differs in its metabolic effect profile from a selective beta 1-blocker and may offer advantages by improving glucose and lipid metabolism.

Adult↗

PubMed1994

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. For 3 to 6 months, 319 hypertensive patients entered 17 study groups, each group using one of the following antihypertensive drugs: dilevalol, metoprolol, antenolol, pindolol, propranolol, hydrochlorothiazide, bendrofluomethiazide, furosemide, spironolactone, doxazocine, prazocine, diltiazem, verapamil, nifedipine, isradipine, captopril, or lisinopril. Treatment with different beta-blockers, as well as diuretics, reduced the fasting urinary calcium excretion (P < .001). However, while the beta-blockers increased the proportion of the ionized form of calcium in blood (Ca2+) (P < .001), Ca2+ was further decreased by diuretic treatment (P < .05). Angiotensin converting enzyme inhibitors caused no major changes in mineral metabolism while of the calcium antagonists studied only verapamil raised the levels of Ca2+ (P < .01). No significant relationship between the changes in mineral metabolism and the reduction in blood pressure was observed in any of the treatment groups. Of the antihypertensive drugs used in the present study, beta-blockers appeared to reverse the basic abnormality with regard to calcium balance, suggesting that the activity of the sympathetic nerve system is involved in the disturbed calcium metabolism seen in hypertensive patients.

Adrenergic beta-Antagonists↗

PubMed1994

Pathogenesis and prevalence of atherosclerosis in hypertensive patients.

Atherosclerosis is important because of its complications that include, for example, myocardial infarction, angina pectoris, stroke, aortic aneurysm, and intermittent claudication. Prospective studies have indicated that the risk-factor patterns for these complications are different in various parts of the cardiovascular tree. For stroke, hypertension is quantitatively the most important risk factor whereas, for intermittent claudication, smoking appears to be by far the most important risk factor. Myocardial infarction, however, is a complication for which a large number of risk factors emerge and none appears to be more important, at least from the statistical point of view, than the others. The prevalence of the different types of complications of atherosclerosis varies considerably among countries. Despite a high prevalence of stroke in Japan and a prevalence of hypertension equal to that in the United States, the prevalence of myocardial infarction is low. This indicates that the importance of hypertension as a risk factor for myocardial infarction is dependent on the presence of other risk factors, such as hypercholesterolemia. In the United States and several European countries, for instance Sweden, there has been a dramatic reduction in the yearly incidence of stroke since the beginning of the 1950s. The time sequence for this change and the change in the number of patients treated for hypertension have been similar in both the United States and Sweden. In contrast, the decrease in the incidence of myocardial infarction began about 15 years later in Sweden than in the United States. In Sweden, the reduced incidence of stroke can be explained by the reduction in the incidence of hemorrhagic stroke only.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗

PubMed1994

Electrolyte changes and metabolic effects of lisinopril/bendrofluazide treatment. Results from a randomized, double-blind study with parallel groups.

The metabolic effects of lisinopril and bendrofluazide therapy were studied in 61 patients with essential hypertension in a randomized, double-blind study with parallel groups. The insulin sensitivity index, measured by hyperinsulinemic euglycemic clamp test, decreased by 22% (P < .01) during bendrofluazide treatment and by 15% (NS) during lisinopril treatment. The initial insulin response at intravenous glucose tolerance test (IVGTT) increased by 21% (P < .05) during lisinopril treatment but decreased by 13% (P < .05) during treatment with bendrofluazide, and in addition, the glucose disappearance rate decreased by 9% (P < .05) in the latter group. During oral glucose tolerance test (OGTT), the area under the glucose curve (AUCglucose) increased by 17% (P = .05) in the bendrofluazide-treated group but decreased by 19% (P = .05) in the lisinopril group, although there was no difference between the drug effects on AUCinsulin. The LDL/HDL cholesterol ratio increased during bendrofluazide treatment. The serum potassium concentration decreased by 10% (P = .0001) during bendrofluazide treatment but increased by 6% (P = .0001) in the lisinopril-treated group. The change in serum potassium was correlated to the change in initial insulin response and glucose disappearance rate at IVGTT, and inversely correlated to the change in AUCglucose at OGTT. In conclusion, alterations in serum potassium balance may affect the initial insulin release and glucose disposal. Bendrofluazide treatment decreases the serum potassium concentration, reduces the initial insulin release and the glucose disposal, and, in addition, impairs insulin sensitivity. Lisinopril treatment increases serum potassium concentration and the initial insulin response, and decreases AUCglucose, but does not improve insulin sensitivity per se.

Bendroflumethiazide↗

PubMed1994

Dose-response of simvastatin in primary hypercholesterolemia.

In an 8-week, placebo-controlled multicenter study, the efficacy of dose levels of simvastatin 2.5, 5, 10, 20, and 40 mg was evaluated in 166 patients with hypercholesterolemia, of whom 163 completed the trial. The entry criteria were serum total cholesterol (TCHOL) between 6.2 and 7.8 mM and low-density lipoprotein (LDL) cholesterol between 4.3 and 50 mM on a standard diet and after the 2-week run-in period of placebo treatment. Mean percentage changes in serum lipids in each simvastatin-treated group from baseline were statistically significant. Of treated patients, 0% (placebo), 11% (2.5 mg), 7% (5 mg), 33% (10 mg), 42% (20 mg) and 55% (40 mg) had at least 40% reduction from baseline LDL cholesterol value. After 8 weeks of treatment, 0% (placebo), 11% (2.5 mg), 25% (5 mg), 26% (10 mg), 31% (20 mg), and 55% (40 mg) of patients treated reached a TCHOL level of < or = 5.2 mM. There was a significant linear dose response with regard to the decrease in LDL cholesterol, TCHOL, and triglycerides (TG) and the increase in high-density lipoprotein (HDL) cholesterol after 8 weeks of therapy. No serious clinical or laboratory adverse events related to simvastatin were observed even at higher doses. At each dose level, simvastatin reduced TCHOL and LDL cholesterol. Doses of simvastatin > or = 5 mg moderately increased HDL cholesterol and reduced serum TG. Simvastatin therapy resulted in major improvement in serum lipoprotein profile, particularly at higher doses.

Anticholesteremic Agents↗

PubMed1994

Serum lipoprotein lipid profile in women with the polycystic ovary syndrome: relation to anthropometric, endocrine and metabolic variables.

OBJECTIVE: Although often associated with insulin resistance and glucose intolerance, various lipoprotein abnormalities have been found in polycystic ovary syndrome (PCOS) but not invariably so when the degree of obesity is taken into account. We have therefore investigated the serum lipid profile in a group of women with polycystic ovary syndrome with and without obesity. DESIGN: Cross-sectional study of serum lipoprotein lipids and plasma free fatty acids in relation to anthropometric, metabolic and hormonal variables in women with PCOS and weight-matched controls. PATIENTS: Twenty-four obese (Pob, mean BMI +/- SD 30.6 +/- 3.3 kg/m2) and 25 non-obese (Pnob, 22.2 +/- 2.3 kg/m2) women with PCOS. Twenty obese (Cob, 30.2 +/- 3.5 kg/m2) and 20 non-obese (Cnob, 21.4 +/- 1.5 kg/m2) controls. MEASUREMENTS: Fasting concentrations of plasma free fatty acids, serum cholesterol and triglycerides in high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) in relation to insulin sensitivity index (M/I; assessed with the euglycaemic insulin clamp), glucose tolerance (k-value; intravenous glucose tolerance test), basal serum hormone concentrations, and body fat distribution (skinfolds and waist hip ratio). RESULTS: Plasma concentrations of free fatty acids were markedly higher in Pob than in the other groups (all P < 0.001). The lipoprotein lipids did not differ between Pob and Cob, or between the non-obese groups, whereas both obese groups had higher serum concentrations of triglycerides, totally and in VLDL, and lower HDL-cholesterol than their non-obese counterparts. Pob also had higher serum levels of total and LDL-cholesterol than Pnob. Pob had a more pronounced subcutaneous truncal-abdominal adiposity, higher fasting insulin levels and lower M/I than the other groups, and a lower k-value than Cob. Cob had higher levels of fasting insulin than Cnob. Free fatty acid levels correlated with the k-value (inversely) in both women with PCOS and controls, and with M/I (inversely), age and testosterone levels in PCOS. Stepwise regression analysis for the total population, comparing endocrine, anthropometric and metabolic explanatory variables, showed that the serum levels of HDL-cholesterol and triglycerides were mainly correlated with body fat distribution (both) and fasting insulin levels (triglycerides), and levels of total and LDL-cholesterol with BMI and age. CONCLUSIONS: Plasma free fatty acid correlations were markedly increased in obese women with PCOS, closely associated with the lower insulin sensitivity and lower glucose tolerance in these women. In spite of these profound metabolic aberrations, the lipoprotein lipid profile was not significantly more abnormal in obese women with PCOS than in their weight-matched controls.

Adult↗

PubMed1994

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. SUBJECTS: Twenty-six untreated hypertensive subjects. INTERVENTIONS: After 4 weeks on placebo, isradipine was titrated up to 10 mg daily to achieve appropriate blood pressure control (n = 11). If this failed, 5-10 mg pindolol was added. The treatments were continued for 2 years. MAIN OUTCOME MEASURES: Blood pressure, lipoprotein measurements, intravenous glucose tolerance test, hyperinsulinaemic euglycaemic clamp, HbA1c, body weight. RESULTS: Treatment with isradipine alone caused a sustained reduction in blood pressure (-22/-10 mm Hg, P < 0.01), but an increase in body weight (+2.2 kg, P < 0.05) and HbA1c (+1.5%; P < 0.001) were also noted. Addition of pindolol resulted in a similar degree of blood pressure reduction and weight gain, whilst HbA1c was less affected (+1.0%; P < 0.05, compared to isradipine alone). Insulin sensitivity became impaired in both groups (-1.2 to -1.5 mg kg-1 min-1; P < 0.01 for M-value at hyperinsulinaemic clamp) but after adjustment for the change in body weight the impairment was only significant (P < 0.01) in the group with combined treatment. The combined treatment also resulted in an increase in very-low-density-lipoprotein (VLDL) triglycerides (+ 0.37 mmol L-1; P < 0.05). CONCLUSIONS: The hypotensive effect of isradipine was sustained during long-term use but was associated with weight gain and an impaired glucose control. When isradipine was combined with pindolol there was also a reduction in insulin sensitivity and an increase in VLDL triglycerides, possibly as effects of the beta-adrenergic blockade.

Adult↗

PubMed1994

Multiple lipolysis defects in the insulin resistance (metabolic) syndrome.

Bearing in mind the importance of upper-body obesity for the insulin resistance (or metabolic) syndrome and the abnormalities in free fatty acid metabolism associated with this disorder, the regulation of lipolysis in isolated subcutaneous adipocytes was investigated in 13 72-yr old upper-body obese men with insulin resistance and glucose intolerance and in 10 healthy 72-yr-old men. There was a marked resistance to the lipolytic effect of noradrenaline in the metabolic syndrome due to defects at two different levels in the lipolytic cascade. First, an 80-fold decrease in sensitivity to the beta 2-selective agonist terbutaline (P < 0.001) which could be ascribed to a 50% reduced number of beta 2-receptors (P < 0.005) as determined with radioligand binding. The groups did not differ as regards dobutamine (beta 1) or clonidine (alpha-2) sensitivity, nor beta 1-receptor number. The mRNA levels for beta 1- and beta 2-receptors were similar in the two groups. Second, the maximum stimulated lipolytic rate was markedly reduced in the metabolic syndrome. This was true for isoprenaline (nonselective beta-agonist), forskolin (activating adenylyl cyclase), and dibutyryl cAMP (activating protein kinase). In regression analysis, the observed abnormalities in lipolysis regulation correlated in an independent way with the degree of glucose intolerance (r = -0.67) and beta 2-receptor number with insulin resistance (r = 0.67). In conclusion, the results of this study indicate the existence of lipolytic resistance to catecholamines in the adipose tissue of elderly men with the metabolic syndrome, which may be of importance for impaired insulin action and glucose intolerance. The resistance is located at a posttranscriptional level of beta 2-receptor expression and at the protein kinase-hormone sensitive lipase level.

Adipose Tissue↗

PubMed1994

Enhanced early insulin response to glucose in relation to insulin resistance in women with polycystic ovary syndrome and normal glucose tolerance.

Insulin secretion in response to iv glucose and insulin sensitivity (euglycemic hyperinsulinemic clamp) were evaluated in 49 women with polycystic ovary syndrome (PCOS) [body mass index (BMI), 17.6-37.2 kg/m2] and 42 control subjects (BMI, 18.8-38.1 kg/m2). Seven women with PCOS exhibited glucose intolerance with subnormal insulin secretion. Compared with control subjects, women with PCOS and normal glucose tolerance had an increased (36-56%) insulin increment, not explained by insulin resistance, and over the whole range of BMI. In contrast, insulin sensitivity was similar in women with PCOS and control subjects at BMI 21 kg/m2, but showed a more pronounced decline with increasing BMI in women with PCOS, who had 35% and 70% lower insulin sensitivities at BMI 28 and 35 kg/m2, respectively. After adjusting for truncal-abdominal sc fat distribution, which was more pronounced in the women with PCOS, the two groups had similar insulin sensitivity over the entire range of BMI (P = 0.9), whereas the difference in insulin increment was insignificant after adjusting for the free androgen index (testosterone x 100/sex hormone binding globulin; P = 0.16). Hemoglobin A1C levels were lower in women with PCOS than in the control subjects. It is concluded that the early insulin response to glucose was increased in women with PCOS, not accounted for by insulin resistance, closely associated to the increased androgenicity, and present also at low-normal BMI. In contrast, insulin resistance was seen only at higher BMI levels and was largely determined by the increased truncal-abdominal fat mass in PCOS.

Adult↗

PubMed1994

The risk to develop NIDDM is related to the fatty acid composition of the serum cholesterol esters.

This investigation was undertaken to study whether the risk to develop non-insulin-dependent diabetes mellitus (NIDDM) among 50-year-old men during a 10-year follow-up period was related to the fatty acid composition of their serum cholesterol esters. There were highly significant differences in the initial health survey between the fatty acid composition in serum in subjects who remained normoglycemic (n = 1,753) and in those who later developed NIDDM (n = 75). The main differences were that the latter had higher proportions of saturated fatty acids and palmitoleic acid (16:1 omega-7), a low proportion of linoleic acid (18:2 omega-6), and a relatively high content of gamma-linolenic (18:3 omega-6) and dihomo-gamma-linolenic (20:3 omega-6) acids in the serum cholesterol esters. The picture was similar also after adjusting for differences in body mass index. In a logistic model, a high proportion of dihomo-gamma-linolenic acid remained a significant contributor to the development of diabetes, along with the height of the insulin index, the blood glucose concentration at 60 min, and the fasting insulin concentration. The increased risk to develop NIDDM related to the serum cholesterol ester fatty acid composition may be mediated by diet and/or genetic factors.

8,11,14-Eicosatrienoic Acid↗

PubMed1994

Angiotensin-converting enzyme in human skeletal muscle. A simple in vitro assay of activity in needle biopsy specimens.

The importance of skeletal muscle for human haemodynamics and metabolism makes it a suitable sample tissue for the measurement of angiotensin converting enzyme (ACE; EC 3.4.15.1). A study of serum and muscle angiotensin-converting enzyme was performed in 50 essential-hypertensive subjects. Muscle tissue was obtained from the vastus lateralis muscle by Bergström needle biopsies. The method used is a modification in Cushman's fluorometric assay for tissue angiotensin-converting enzyme. It utilized 5 mM hippuryl-histidyl-leucine as a synthetic substrate for a 60-min fixed-time incubation at 37 degrees C. The 0.25 ml incubation mixture consisted of 0.12 mM potassium phosphate buffer, pH 8.1, 300 mM NaCl, and 1 or 2 mg homogenized muscle tissue. The activity was found to have the properties previously reported for human ACE. The intra- and interassay coefficients of variation of the method were 13% and 21%, respectively, for the 1 mg incubation as assessed from internal controls (n = 20). the muscle ACE activity in the hypertensive subjects was 49 +/- 14 mU g-1 (mean +/- SD) with no difference between values for men and women. No correlation was found between muscle ACE activity and age, or between muscle and serum angiotensin-converting enzyme activity. We consider this assay a useful new tool for investigating the role of angiotensin-converting enzyme in the pathogenesis and treatment of hypertension, as it can be applied to patient materials.

Biopsy, Needle↗

PubMed1994

Electrocardiographic changes during antihypertensive treatment with diltiazem in relation to the achieved serum levels of the drug.

Diltiazem is a calcium channel blocker with antihypertensive and antiarrhythmic actions. In the present study 24 hypertensive patients were treated with diltiazem (180-360 mg daily) for 6 months. The effects on the electrocardiogram (ECG) were studied and were related to the serum levels of diltiazem. Treatment with diltiazem induced a non-significant reduction in heart rate with 3 beats min-1 and decreased blood pressure (-11/-9 mm Hg, p < 0.001). The treatment also induced a prolongation of the PQ-interval (+1.4 cs, p < 0.02), a prolongation only being weakly related to the plasma levels of diltiazem (r = 0.28, not significant) and its metabolite MA (r = 0.37, p = 0.07). Neither was the induced increase in the QT-interval (+0.9 cs, p < 0.05), significantly related to the plasma levels of diltiazem. In conclusion, the plasma levels of diltiazem were not clearly related to the induced changes at the ECG during antihypertensive treatment.

Adult↗

PubMed1994

Impaired glucose and lipid metabolism seen in intensive care patients is related to severity of illness and survival.

OBJECTIVE: To relate glucose and lipid metabolism to the severity of illness and survival in critically ill patients. DESIGN: Cross-sectional and prospective cohort study. SETTING: Secondary referral ICU. PATIENTS: Forty-four consecutive patients admitted to the ICU. MEASUREMENTS AND MAIN RESULTS: An intravenous glucose tolerance test (IVGTT) and serum lipoprotein determinations were performed within the first 24 hours in the ICU. An APACHE II score was also determined. Basal serum lactate, glucose and insulin were all elevated in ICU patients compared to healthy controls (p < 0.001) and were all correlated to indices of severity of illness (r = 0.36-0.42, p < 0.05-0.01 vs the APACHE II score). However, the early insulin response to IVGTT was inversely correlated to the APACHE II score (r = -0.50, p < 0.01). Triglyceride and cholesterol levels in serum were generally decreased when compared to controls (0.88 +/- 0.63 mmol/l for serum triglycerides and 2.46 +/- 0.97 mmol/l for serum cholesterol, p < 0.01 vs controls). However, as could be judged from the levels of free serum glycerol (0.27 +/- 0.23 mmol/l), lipolysis was increased in the critically ill. Serum triglyceride levels, as well as serum FFA and glycerol, correlated to the severity of illness (r = 0.36-0.62, p < 0.05-0.001), HDL-cholesterol was inversely related to the APACHE II score (r = -0.40, p < 0.05). Serum glucose, FFA, glycerol and triglycerides in serum, VLDL and LDL were all elevated (p < 0.05-0.001), while HDL-cholesterol was decreased (p < 0.05) in septic patients (n = 17) compared to those without sepsis. Serum lactate (p < 0.05) and free glycerol (p < 0.01) were both elevated in patients who did not survive (n = 6) when compared to survivors. Multiple logistic regression analysis showed free glycerol (p < 0.05) to be additive to the APACHE II score (p < 0.01) in predicting mortality. CONCLUSION: In a sample of unselected critically ill patients indices of both glucose and lipid metabolism were found to be related to the severity of illness as well as to the occurrence of sepsis and survival.

APACHE↗

PubMed1994

Effects of selective alfa 1 and beta 1-adrenoreceptor blockade on lipoprotein and carbohydrate metabolism in hypertensive subjects, with special emphasis on insulin sensitivity.

The central role of insulin resistance in patients with essential hypertension was the impetus for the present study, in which carbohydrate and lipid metabolism were examined before and after three months treatment with doxazosin (n = 14) and atenolol (n = 15). After completion of a randomised parallel group trial, the study was extended in a subgroup of the patients who continued treatment with doxazosin for a further nine months (n = 18). Insulin sensitivity was measured with the euglycemic hyperinsulinaemic clamp. Blood glucose and plasma insulin were analysed in the fasting state and during an intravenous glucose tolerance test (IVGTT). Lipoprotein fractions were analysed in serum. After three months, SBP and DBP in the standing position decreased to the same extent after the two drugs whereas the decrease in supine SBP did not reach statistical significance in the doxazosin group. Doxazosin, in contrast to atenolol, decreased serum triglycerides (-17%, P < 0.04) by lowering the VLDL and LDL fractions. Serum cholesterol fell after doxazosin (-7%, P < 0.02) but not after atenolol. The effects of doxazosin on serum lipids remained the same during the long-term follow-up. At three months neither drug had significantly affected variables reflecting insulin sensitivity although atenolol tended to decrease the insulin sensitivity index (-17%, P = 0.08). After 12 months the doxazosin group showed a significant increase in the insulin sensitivity index and a significant decrease in both basal plasma insulin and in the late insulin response at IVGTT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗