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Biomedical subjects

H Lithell

Publications and source records attributed to H Lithell.

At least 109 records · Page 6Linked to original sources
PubMed1996

Insulin sensitivity following treatment with the alpha 1-blocker bunazosin retard and the beta 1-blocker atenolol in hypertensive non-insulin-dependent diabetes mellitus patients.

OBJECTIVE: To compare the effects of the alpha 1-blocker bunazosin retard and the beta 1-blocker atenolol (Uniloc) on insulin sensitivity and glucose and lipid homeostasis in patients with type-2 diabetes and hypertension. METHODS: Patients with controlled type-2 diabetes (non-insulin-dependent diabetes mellitus), treated by diet or oral sulphonylurea derivatives, and with mild-to-moderate hypertension were include in a randomized, parallel group, double-blind, multicentre study. After a single-blind placebo run-in period lasting 4-6 weeks, the patients were treated either with bunazosin retard or with atenolol for a further 16 weeks including an initial dose titration period to achieve blood pressure control. Treatment involved 3, 6 or 12 mg bunazosin retard tablets or 25, 50 or 100 mg atenolol tablets, administered orally once a day and prescribed according to blood pressure response. The euglycaemic hyper-insulinaemic clamp technique was used to assess insulin sensitivity both after the placebo period and after the active treatment. A total of 95 patients was enrolled in the study (placebo phase). Forty-eight patients were withdrawn from the placebo phase, mainly due to their blood pressures being outside the required range (seated diastolic blood pressure 90-114 mmHg) and 47 patients were allocated randomly to active treatment. Of these, 23 were administered bunazosin retard and 24 atenolol. All evaluations were on an intention-to-treat basis. RESULTS: Insulin sensitivity assessed as glucose utilization during the clamp was significantly higher following bunazosin retard compared with following atenolol administration (3.52 +/- 0.27 versus 2.86 +/- 0.19 units of metabolic clearance rate of glucose index, P < 0.05). The insulin level attained during clamps (infusion rate 56 mU/m2 per min) was higher (P < 0.05) following atenolol (117 +/- 5 mU/l) than it was following bunazosin retard administration (102 +/- 5) or placebo (108 +/- 3), possibly due to an impaired insulin clearance. Compared with placebo, atenolol treatment resulted in significantly increased glucosylated haemoglobin whereas bunazosin retard had no significant effect. The two drugs did not show any consistent differences in lipid profile or fibrinogen and plasminogen activator inhibitor 1 levels. During the study seven serious adverse events were reported and one was reported shortly after completion of the study. All except one were classified as not related to the study drug and five of them occurred during placebo treatment. The non-serious side effects were in general considered to be either unrelated to the test drugs or expected effects of the two respective drug classes. Both bunazosin retard and atenolol displayed acceptable safety profiles. CONCLUSION: Bunazosin retard treatment in hypertensive non-insulin-dependent diabetes mellitus patients appears to be associated with a slightly higher insulin sensitivity than is atenolol.

Adrenergic alpha-Antagonists↗
PubMed1996

Prediction models for insulin resistance.

A prediction model for estimating insulin resistance in hypertensive patients is presented. Body-mass index, serum triglyceride concentrations and liver enzyme activity in plasma correlate to insulin resistance determined with the euglycaemic, hyperinsulinaemic clamp technique. Prediction models using body-mass index and either triglycerides or serum alanine-amino transferase were equally good in predicting insulin resistance and gave results that were as reliable as those obtained in a model using fasting-insulin concentrations. The hyperinsulinaemic clamp had a reproducibility error of 14%, and body-mass index and serum triglycerides had a multiple correlation of 0.57 to the insulin-sensitivity results. The model predicts insulin resistance with acceptable statistical power, whereas the power to predict high values of insulin sensitivity is less good.

Aged↗
PubMed1996

Reduced cholesteryl ester transfer in plasma of patients with lipoprotein lipase deficiency.

The net mass transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to the apolipoprotein (apo) B-containing lipoproteins, very low density lipoprotein (VLDL) and low density lipoprotein (LDL) in plasma (cholesteryl ester transfer (CET)) from three patients lacking lipoprotein lipase (LpL) activity was significantly lower (P < 0.001) than in plasma from fasting control subjects with comparable triglyceride levels. Chylomicrons isolated from LpL-deficient fasting plasma showed the same low level of CET activity as observed in the intact plasma when combined with HDL and cholesteryl ester transfer protein (CETP)-containing d 1.063 g/ml bottom fractions from control subjects. Preincubation of chylomicrons and large triglyceride-rich lipoproteins (Sf > 400) from LpL-deficient plasma with milk LpL, however, stimulated the capacity to engage in CET 4- to 5-fold to the same level as chylomicrons and VLDL from control subjects after a fat load. Consistent with these measurements of CET activity in plasma, chylomicrons obtained from the LpL-deficient subjects after a 14-h fast had higher TG/CE ratios than chylomicrons from controls 3 h after ingesting a fat load (LpL-deficient 26.3 +/- 9.0 vs. controls 6.9 +/- 2.1; mean +/- SD). The mass of CETP did not differ in LpL-deficient and control subjects (LpL-deficient 1.03 +/- 0.22 micrograms/ml vs. controls 1.58 +/- 0.58 micrograms/ml). These studies are consistent with earlier in vitro studies showing that the actions of lipoprotein lipase and its lipolytic products are essential, for maximal cholesteryl ester transfer protein activity.

Cholesterol Esters↗
PubMed1995

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. Since significant gender differences were present in a number of parameters of lipoprotein composition, male and female data were examined separately. The EH group of both sexes tended to have higher plasma TG and VLDL + LDL and HDL2 lipid levels than their respective controls. Not only were the calcium-binding phospholipids phosphatidylinositol (PI) + phosphatidylserine (PS), and the membrane fluidizer phosphatidylethanolamine (PE) were significantly reduced in their VLDL + LDL, but all phospholipids (L, sphingomyelin (SPH), PI + PS, and PE) were significantly reduced in their neutral lipid content in both the HDL2 and HDL3 subfractions. These directional changes in lipoprotein FC and phospholipid in the EH women significantly increased the EH FC/PC (mol/mol) ratio in their plasma, a new cardiovascular risk factor, (EH 1.08 +/- 0.22 vs. control 0.86 +/0 0.08; P < 0.01) and lowered the SPH/PC ratio HDL2 and HDL3 in EH patients of both sexes. These findings showed that lipoproteins in normolipidemic EH women are relatively enriched in FC and in EH patients of both sexes depleted in certain phospholipids lacking in lipoproteins, their functional properties could be altered and vascular tone increased.

Aged↗
PubMed1995

A comparison between the effects of gemfibrozil and simvastatin on insulin sensitivity in patients with non-insulin-dependent diabetes mellitus and hyperlipoproteinemia.

In a double-blind, randomized crossover study, 29 patients with non-insulin-dependent diabetes mellitus (NIDDM) and hyperlipoproteinemia were treated with gemfibrozil (1,200 mg/d) or simvastatin (10 mg/d) for 4 months. After gemfibrozil treatment, the insulin concentration was increased during the major part of the intravenous glucose tolerance test (IVGTT) and during the hyperinsulinemic euglycemic clamp. Similar but less pronounced elevations were caused by simvastatin. Insulin sensitivity decreased by 27% and 28% during gemfibrozil and simvastatin treatment, respectively. Low-density lipoprotein (LDL) cholesterol was decreased with simvastatin treatment by 24%. The LDL cholesterol level was not changed by gemfibrozil, but very-low-density lipoprotein (VLDL) cholesterol was reduced by 40%. The VLDL triglyceride concentration was reduced to a significantly greater extent by gemfibrozil. After gemfibrozil treatment, lipoprotein(a) [Lp(a)] was decreased by 24%, and the plasma free fatty acid (FFA) concentration was increased by 20% and skeletal muscle lipoprotein lipase activity (LPLA) by 37%. Although simvastatin more effectively decreased LDL cholesterol levels and the LDL to high-density lipoprotein (HDL) ratio, it cannot be claimed unreservedly that this drug is necessarily preferable in NIDDM patients. Gemfibrozil improved triglyceride removal and decreased VLDL concentrations, with qualitative changes in LDL. The apparent effects on insulin sensitivity are difficult to evaluate and need further study.

Aged↗
PubMed1995

Vitamin D is related to blood pressure and other cardiovascular risk factors in middle-aged men.

A previous study has shown that serum levels of the active vitamin D metabolite 1,25-(OH)2-vitamin D were inversely related to blood pressure levels while the prohormone 25-OH-vitamin D was found to be related to insulin metabolism. Also other clinical and experimental data support the view that vitamin D metabolism is involved in blood pressure regulation and other metabolic processes. The present study was conducted in order to see if the above mentioned relationships between the vitamin D endocrine system and blood pressure, as well as other cardiovascular risk factors, could be found in a cross-section population-based study. Serum levels of 1,25-(OH)2-vitamin D, 25-OH-vitamin D, and blood pressure were therefore measured in 34 middle-aged men and metabolic cardiovascular risk factors were evaluated by means of intravenous glucose and fat tolerance tests, euglycemic hyperinsulinemic clamp, lipoprotein measurements, and lipoprotein lipase activity determinations. Serum levels of 1,25-(OH)2-vitamin D were found to be inversely correlated to the blood pressure (r = -0.42, P < .02), VLDL triglycerides (r = -0.47, P < .005), and to triglyceride removal at the intravenous fat tolerance test (r = 0.34, P < .05), while serum levels of 25-OH-vitamin D were correlated to fasting insulin (r = -0.35, P < .05), insulin sensitivity during clamp (r = 0.54, P < .001), and lipoprotein lipase activity both in adiposal tissue (r = 0.48, P < .005) and skeletal muscle (r = 0.38, P < .03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1995

Metabolic aspects of the treatment of hypertension.

INSULIN RESISTANCE AND HYPERTENSION: Hypertension is often associated with insulin resistance, which may be the underlying cause of hypertension in many cases. The whole complex of insulin resistance and its related factors appears to be based on a reduction in nutritional blood flow to large muscle groups. EFFECT OF TREATMENT: Blood flow is further reduced during beta-blockade but improves during alpha 1-blockade, which may explain the contrasting effects of these treatments on insulin resistance and triglyceride metabolism.

Adrenergic alpha-Antagonists↗
PubMed1995

Hyperlipidaemia in renal transplantation--risk factor for long-term graft outcome.

The role of hyperlipidaemia for the outcome of renal transplantation was evaluated in a prospective study involving 151 patients. Graft losses were associated with more pronounced pre-transplant lipid abnormalities. An increased risk of graft loss during the first two post-transplant years was found in patients with marked pre-transplant hypercholesterolaemia (> or = 6.9 mmol L-1, P = 0.014; relative risk 2.2). Hypercholesterolaemia > or = 6.9 mmol L-1 at 6 months after transplantation, present in 41/115 patients, was associated with a lower GFR (P = 0.007) and more pronounced albuminuria (P = 0.009) at 2 years. In patients with graft dysfunction (serum creatinine > 160 mumol L-1) at 2 years, more pronounced lipid abnormalities before and at 6 months after transplantation were found. Between 6 months and 2 years, total and LDL cholesterol did not change significantly, but HDL cholesterol decreased (P = 0.03). In conclusion, hyperlipidaemia is also a risk factor for the long-term outcome in renal transplantation. Further investigations are needed to determine whether graft losses and late graft failure can be prevented or ameliorated by treating hyperlipidaemia in renal transplantation.

Adolescent↗
PubMed1995

The influence of body composition on left ventricular mass and other echocardiographic and Doppler measurements in 70-year-old males.

Heart morphology and function are often related to body size. The most common way to standardize for body composition is to divide these measures by body surface area (BSA). It has, however, been suggested that left ventricular mass (LV mass) ought to be indexed for height and that cardiac output is influenced by the body fat distribution. As part of a health screening programme of 70-year-old males in Uppsala, Sweden, 100 consecutive men were investigated with echocardiography and Doppler with regard to cardiac morphology and function. These measures were related to an evaluation of body composition using an X-ray method (dual energy X-ray absorptiometry). Lean body mass was strongly related to BSA and body weight (r = 0.90 and 0.89, respectively; P < 0.0001), and to a lesser degree to height (r = 0.70, P < 0.0001). In the healthy part of the population (n = 39), relationships between LV mass on the one hand and lean body mass, BSA and height on the other were seen (r = 0.51, 0.51 and 0.50, respectively; P < 0.01). Stroke volume calculated according to Teichholtz (but not when calculated with Doppler) showed a significant correlation to lean body mass (r = 0.38, P < 0.05). Also, left ventricular diameter and the thickness of the free wall were related to lean body mass (r = 0.40 and 0.39, respectively; P < 0.05). All of the evaluated relationships were generally weaker and in most cases no longer significant when evaluated in part of the population with diseases known to affect the heart. No significant correlations were seen between the size of the left atrium, septal thickness or indices of diastolic function (E/A-ratio, isovolumic relaxation time, deceleration time) and the indices of body composition. No measures of cardiac morphology and function were significantly related to the amount of body fat or body bone. LV mass, stroke volume and left ventricular diameter were found to be correlated with lean body mass, but not with the amount of fat, in healthy 70-year-old males. Theoretically, it is optimal to adjust for lean body mass, but in clinical practice, BSA is to be preferred.

Aged↗
PubMed1995

C4 null alleles in a Swedish population.

The distribution of C4 null alleles (C4Q0) was studied in a Swedish population comprising 410 male individuals from Stockholm County and Uppsala City. The prevalances of homozygous C4A*Q0 and C4B*Q0 determined by analysing the gene products in serum were 5.0 and 5.6%, respectively, in the Stockholm population and 4.0% each in the Uppsala population. These values are higher than those previously reported from other Caucasian populations. The finding reflects a different genetic composition of the Swedish population and may have relevance to the disease spectrum in this population as compared to other Caucasian populations.

Adult↗
PubMed1995

Restored insulin sensitivity but persistently increased early insulin secretion after weight loss in obese women with polycystic ovary syndrome.

The impact of weight reduction on metabolic, endocrine, and anthropometric variables was studied in 13 obese, insulin-resistant women with the polycystic ovary syndrome (PCOS). Insulin sensitivity (euglycemic insulin clamp), insulin secretion and glucose tolerance (iv glucose tolerance test), basal sex steroid hormones, gonadotropins and free fatty acids (FFA), skin folds and waist hip ratio (WHR) were evaluated before (PCO-BD) and after (PCO-AD) diet-induced weight reduction to a weight stable level [mean (SD) diet duration 14.9 (6.2) months]. Mean weight loss was 12.4 kg (4.7; P < 0.0001), equalling a reduction from a body mass index (BMI) of 32.2 (3.7) kg/m2 to 27.6 (3.7; P < 0.0001) kg/m2. The results were compared with those of two groups of weight stable (no diet) women, 21 with PCOS (PCO-ND) and 23 normal control subjects (C), who were matched to the BMI the diet group reached after weight loss. Insulin sensitivity index (M/I) improved on average 132% (P < 0.001) and plasma FFA by 32% (P < 0.01), serum sex hormone binding globulin levels increased by 35% (P < 0.01), and the sum of truncal-abdominal skin-folds (subscapular, umbilical, and suprailiacal) were reduced by 28% (P < 0.0001), whereas the early insulin response to iv glucose, the levels of gonadotropins and androstenedione, and the femoral sc fat did not change significantly with weight loss. M/I, levels of SHBG and FFA and truncal-abdominal fat reached levels similar to the controls, whereas PCO-ND had lower M/I (P < 0.01) and SHBG levels (P < 0.0001), greater concentrations of FFA (P < 0.01) and truncal-abdominal fat (P < 0.05) than C. Among women with normal glucose tolerance, the insulin increment was higher in both PCO-AD (P < 0.05) and PCO-ND (P < 0.01) than in C. There was a strong correlation between M/I and sum of truncal-abdominal skinfolds in all groups (PCO-BD: r = 0.82; P < 0.001, PCO-AD: r = 0.68; P < 0.05, PCO-ND: r = 0.81; P < 0.0001, C: r = 0.44; P < 0.05). The variation in M/I in PCO-AD and PCO-ND (pooled) was best explained by FFA and truncal-adbominal fat (model R2 = 0.67). In conclusion, insulin resistance in obese women with PCOS was reduced by weight loss to similar levels as BMI-matched control subjects, suggesting that insulin resistance in PCOS is not a feature of PCOS per se.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

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 < 0.0001). Whereas both drugs significantly increased the levels of glycolysated haemoglobin (HbA1c, +0.24%, P < 0.005 for nifedipine and +0.43%, P < 0.001 for furosemide), only furosemide increased fasting blood glucose (+0.3 mmol/L, P < 0.01) and fasting insulin (+2.2 mU/L, P < 0.05) but impaired the early insulin response to i.v. glucose (-15 mU/L, P < 0.05). Insulin sensitivity on the other hand was significantly impaired by nifedipine treatment only (-1.6 mg/kg/min, P < 0.01). Whereas treatment with nifedipine did not change serum lipids, furosemide caused an increase in serum cholesterol (+0.2 mmol/L, P < 0.05) because of a rise in the LDL fraction (+0.32 mmol/L, P < 0.001). The insignificant change in heart rate induced by nifedipine treatment correlated with the change in HbA1c (r = 0.50, P = 0.05) and was inversely related to the change in insulin sensitivity (r = -0.56, P < 0.05). In conclusion, both furosemide and nifedipine caused abnormalities in glucose metabolism. In the nifedipine group the effects on glucose metabolism were related to the occurrence of tachycardia suggesting that sympathetic nerve activation could be involved in the metabolic impairments.

Aged↗
PubMed1995

Different long-term metabolic effects of enalapril and atenolol in patients with mild hypertension. EGTA Group.

The primary objective in this multicentre, double-blind randomised, parallel study was to compare the metabolic effects of 12 months of treatment with an ACE inhibitor (enalapril) with those of a selective beta-blocker (atenolol) in patients with mild hypertension. The patients (35-69 years of age) were included if they were without antihypertensive drugs and after six months of nonpharmacological treatment had supine DBPs between 90 and 104 mmHg; 220 patients were randomised to enalapril (20 or 40 mg/day) and 218 to atenolol (50 or 100 mg/day). After 12 months of treatment, atenolol significantly increased the glucose concentrations at 60, 90 and 120 minutes after an oral intake of 75 g glucose (P < 0.01), while enalapril did not. Atenolol significantly increased fasting blood glucose and insulin concentration 120 minutes after glucose intake, while enalapril did not. Plasma total cholesterol and triglycerides increased significantly in patients having atenolol but not in those having enalapril. HDL cholesterol decreased significantly in the atenolol group but not in the enalapril group. The proportions of patients with clinical adverse experiences were similar in both treatment groups. These results indicate that enalapril does not influence either glucose tolerance or lipoprotein metabolism while atenolol does. These findings are consistent over the 12 month treatment period and confirm earlier short-term study results.

Adult↗
PubMed1995

Is insulin resistance a predictor of the blood pressure response to anti-hypertensive treatment?

It is a general impression that the blood pressure (BP) response during monotherapy in hypertensive subjects is highly variable. As decreased insulin sensitivity is a frequent finding in hypertensive patients, the following study was performed to evaluate if the degree of insulin sensitivity could predict the BP response to different types of anti-hypertensive treatments. Insulin sensitivity was evaluated by the hyperinsulinaemic euglycaemic clamp technique before initiation of treatment with beta-adrenergic blockers (n = 181), thiazide diuretics (n = 60), ACE inhibitors (n = 73), non-dihydropyridine calcium antagonists (n = 38), dihydropyridine calcium antagonists (n = 26) or alpha-1 antagonists (n = 39) over periods of 3-6 months in hypertensive patients. The proportion of poor responders, defined as a reduction in the diastolic blood pressure (DBP) of < 3 mm Hg ranged between 8% and 30% in the different groups despite similar pretreatment DBPs (100-102 mm Hg). A decreased pretreatment insulin sensitivity was related to a poor DBP treatment response in the thiazide-treated group only (r = -0.33, P < 0.05). In this group also obesity, as evaluated by body mass index (BMI), was associated with a poor BP response (r = 0.28, P < 0.05), while obesity was a predictor of a favourable reduction in DBP in the group treated with non-dihydropyridine calcium antagonists (r = -0.34, P < 0.05). These associations were still significant when pretreatment DBP was taken into account in multiple regression analysis. Neither age nor sex were found to be significant predictors of BP response in any of the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Prevalence of insulin resistance in essential hypertension.

OBJECTIVE: To establish the prevalence of insulin resistance in hypertensive subjects. DESIGN AND METHODS: The euglycaemic hyperinsulinaemic clamp was performed in 420 hypertensive patients taking no antihypertensive medication and in 51 age- and sex-matched healthy controls. No subjects with known diabetes mellitus or fasting hyperglycaemia were included in the study. RESULTS: The mean value for insulin-mediated glucose uptake (M-value at clamp) in the healthy control group (8.2 mg/kg per min) -2 SD was chosen as the cutoff limit for insulin resistance (4.4 mg/kg per min). At this cutoff limit, 27% of the hypertensive subjects were insulin resistant (mean value 3.1 mg/kg per min in this group, range 0.7-4.3). A similar prevalence of insulin resistance in hypertensive patients was found (31%) if the 95th percentile of the non-normally distributed insulin sensitivity index (M/I at clamp) was used to define the cutoff limit for insulin resistance: (4.4 mg/kg per min)/(mU/l x 100). In the insulin-resistant group, 50% showed elevated levels of serum triglycerides (> 2.0 mmol/l), 50% had abdominal obesity (waist:hip ratio > 0.95), 20% had elevated levels of serum uric acid (> 400 mumol/l) and 48% had low high-density lipid (HDL)-cholesterol levels (< 1.0 mmol/l). Half of the insulin-resistant hypertensives but only 20% of the non-insulin resistant group had two or more of these other four metabolic impairments (P < 0.001). Insulin resistance in hypertension was also associated with an increased heart rate (+3 beats/min faster than in non-insulin resistant hypertensive patients, P < 0.01), but no significant differences in blood pressure were found between insulin resistant and non-insulin resistant hypertensive patients. CONCLUSION: When insulin resistance was defined as an M-value at clamp of < 4.4 mg/kg per min, based on calculations from a healthy control sample, about 25% of a sample of hypertensive subjects, taking no antihypertensive treatment and with no history of diabetes mellitus or hyperglycaemia, was found to be insulin resistant. This group of insulin-resistant hypertensives also displayed a high degree of clustering of other metabolic impairments.

Adult↗