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Biomedical subjects

H Lithell

Publications and source records attributed to H Lithell.

At least 73 records · Page 4Linked to original sources
PubMed1998

Left ventricular geometry and function are related to electrocardiographic characteristics and diagnoses.

We investigated the relationships between echocardiographic indices of left ventricular geometry and function and major electrocardiographic (ECG) abnormalities in 540 elderly (69-74 years old) male participants of a health survey conducted in Uppsala county, Sweden. Comparing men with major ECG abnormalities that were present or absent in various hierarchic mutually exclusive categories, left ventricular mass indexed to body surface area (LVMI) was significantly increased with major Q-waves (P = 0.0002), ST or T-wave abnormalities (P = 0.005), left bundle-branch block (P = 0.005) and also with atrioventricular block type 1 (P = 0.008) and frequent premature beats (P = 0.02). The left atrial diameter was also significantly increased with most ECG abnormalities. The increased LVMI was in left bundle-branch block mainly due to an increased left ventricular diameter, whereas left ventricular wall thickness was increased with frequent premature beats, atrioventricular block type 1 and ST or T-wave abnormalities. The prevalence of Q-waves was highest in eccentric left ventricular hypertrophy, whereas the prevalence of ST or T-wave abnormalities and atrioventricular block type 1 was highest in concentric left ventricular hypertrophy. Both left ventricular systolic (ejection fraction) and diastolic function (E/A) ratio) were inversely related to Sokolow-Lyon QRS amplitude (r = -0.25, P < 0.02 and r = -0.22, P < 0.03 respectively). In conclusion, LVMI was increased in subjects with ECG signs of coronary artery disease as well as in subjects with several other ECG diagnoses. Furthermore, both left ventricular systolic and diastolic dysfunction were related to increased QRS amplitudes. Thus, the finding of ECG abnormalities in elderly men should raise the suspicion of structural and/or functional left ventricular abnormality.

Adult↗
PubMed1998

Comparison of effects of quinapril and metoprolol on glycaemic control, serum lipids, blood pressure, albuminuria and quality of life in non-insulin-dependent diabetes mellitus patients with hypertension. Swedish Quinapril Group.

OBJECTIVE: To compare the long-term effects of the angiotensin-converting enzyme (ACE)-inhibitor quinapril and the cardioselective beta-adrenergic blocking agent metoprolol on glycaemic control, with glycosylated haemoglobin (HbA1c) as the principal variable, in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension. DESIGN: A randomized, double-blind, double-dummy, multicentre study during 6 months preceded by a 4 week wash-out and a 3 week run-in placebo period. Quinapril (20 mg) and metoprolol (100 mg, conventional tablets) were given once daily. No change was made in the treatment of diabetes (diet and hypoglycaemic agents). SUBJECTS: Seventy-two patients fulfilling the criteria were randomized and entered the double-blind period. Twelve patients did not complete the study. Sixty patients, 26 on quinapril and 34 on metoprolol, were available for the final analysis. MAIN OUTCOME MEASURES: The effect was assessed by changes in HbA1c, the fasting serum glucose and the post-load serum glucose, C-peptide and insulin levels during the oral glucose tolerance test. RESULTS: In the quinapril group, the fasting serum glucose, oral glucose tolerance and the C-peptide and insulin responses, determined as the incremental area under the curves (AUC), showed no change, but the mean HbA1c level increased from 6.2 +/- 1.1% to 6.5 +/- 1.3% (P < 0.05). In the metoprolol group, the rise in the mean level of HbA1c, from 6.3 +/- 1.0% to 6.8 +/- 1.3% (P < 0.01), tended to be more marked than after quinapril, although there was no significant difference between the increments. The mean fasting serum glucose showed an increase from 9.1 +/- 1.9 mM to 10.1 +/- 2.8 mM (P < 0.01) which correlated significantly with the duration of diabetes (P < 0.01) and the increase in fasting serum triglycerides (P < 0.001). Moreover, in the metoprolol group we found significant decreases in the oral glucose tolerance as well as C-peptide and insulin responses to the glucose load. CONCLUSIONS: Treatment with quinapril for 6 months appears to have advantages over metoprolol in NIDDM patients with hypertension. Although treatment with quinapril or metoprolol over 6 months was concomitant with a rise in the HbA1c, increased fasting blood glucose, decreased oral glucose tolerance and decreased C-peptide and insulin responses to a glucose challenge were observed only in patients treated with metoprolol.

Adrenergic beta-Antagonists↗
PubMed1998

Validation of an oscillometric blood pressure measuring device: a substudy of the HOT Study. Hypertension Optimal Treatment.

The accuracy of a semi-automated oscillometric blood pressure measuring device (Visomat OZ D2 International) was studied by simultaneous comparison with a standard sphygmomanometer in 407 normotensive subjects and hypertensive patients. Four pairs of measurements, at least 1 min apart, were obtained from all patients. The oscillometric device tended to give lower measurements than the standard device; the mean difference was -0.9 mmHg for diastolic blood pressure and -6.4 mmHg for systolic blood pressure. The size of this difference was not dependent on the mean blood pressure. Intra-individual standard deviations were similar with the two techniques. The oscillometric device tended to produce higher readings on the first measurement than on the subsequent three, whereas the reverse was true of the standard sphygmomanometer. It is concluded that the oscillometric device used in the HOT Study provides reliable measurements of blood pressure. The slight difference in mean readings between the two methods is unlikely to be of importance for the comparison of differences in treatment blood pressure values in the HOT Study.

Automation↗
PubMed1998

Atherogenic lipid fractions are related to ionized magnesium status.

The plasma concentration of ionized magnesium (iMg++), the serum total magnesium concentration (tMg), and lipoprotein status were assessed in 29 elderly men with impaired insulin sensitivity but who were otherwise healthy and not receiving antidiabetic pharmacologic treatment. Plasma iMg++ was inversely correlated with serum concentrations of VLDL cholesterol (r = -0.39, P < 0.04), LDL cholesterol (r = -0.57, P < 0.002), total cholesterol (r = -0.55, P < 0.002), VLDL triacylglycerol (r = -0.36, P < 0.05), LDL triacylglycerol (r = -0.48, P < 0.01), and total triacylglycerol (r = -0.41, P < 0.03). The serum total magnesium concentration also tended to be inversely correlated with these lipid fractions, but not significantly so. Furthermore, iMg++ was inversely correlated with the apolipoprotein B concentration (r = -0.56, P < 0.002) and with the ratio of apolipoprotein B to A-I in serum (r = -0.58, P < 0.001). The corresponding values for tMg were r = -0.37 (P = 0.05) and r = -0.37 (P = 0.05), respectively. Insulin increment and the area under the insulin curve during an intravenous glucose tolerance test were inversely correlated with iMg++ [r = -0.56 (P < 0.01) and r = -0.64 (P < 0.0005), respectively], but were not significantly correlated with tMg. Insulin-mediated glucose uptake and the insulin sensitivity index during the hyperinsulinemic euglycemic clamp test were not significantly correlated with tMg (r = 0.05 and 0.12, respectively; NS) nor with iMg++ (r = 0.23 and 0.31, respectively; NS). Atherogenic lipid fractions and some glucometabolic variables were more closely correlated with iMg++ than with tMg.

Aged↗
PubMed1998

Is there a role for leptin in the endocrine and metabolic aberrations of polycystic ovary syndrome?

Immunoreactive serum leptin was analysed in 49 women with polycystic ovary syndrome (PCOS) distributed on a wide range of body mass index (BMI; kg/m2) and in 32 normally menstruating women with comparable age, BMI, physical activity and dietary habits. All women with PCOS had increased androgen concentrations and obese women with PCOS (BMI > or = 25, n=24) also showed decreased insulin sensitivity and a preferential accumulation of truncal-abdominal body fat. Anthropometric and hormonal variables, insulin sensitivity, and pancreatic beta-cell activity were investigated in all women. Percentage body fat was calculated using gender-specific regression equations based on skinfold measurements. Serum leptin concentrations were higher in obese than in non-obese women (P < 0.001), but did not differ between the women with PCOS and controls, nor did they differ between glucose intolerant and glucose tolerant, or hirsute and non-hirsute women with PCOS. Both groups showed strong correlations between serum leptin concentrations and percentage body fat, BMI, body fat distribution, fasting plasma insulin and C-peptide, early insulin secretion, the free androgen index (FAI), and the degree of insulin resistance. After correcting for percentage body fat, only the FAI in the women with PCOS remained significant (P < 0.05). However, in a multiple regression analysis with both percentage body fat and the FAI as independent variables, the FAI increased only minimally (2%) the explained variation in leptin concentrations. Thus, serum leptin concentrations are almost exclusively determined by the total amount of body fat, independent of its location, and do not confirm the hypothesis that leptin is involved in the development of the hormonal and metabolic abnormalities in the PCOS.

Adolescent↗
PubMed1998

Plasminogen activator inhibitor-1 activity is independently related to both insulin sensitivity and serum triglycerides in 70-year-old men.

Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been discussed as a part of the insulin resistance syndrome. However, it is not clear whether the relationship between PAI-1 and insulin resistance is independent of or mediated by increased triglycerides levels. The aim of this study was to investigate whether PAI-1 activity is associated with insulin sensitivity independently of serum triglycerides (sTG) and of other potential confounders. Seventy-year-old men (n=871), participating in a cohort study undergoing extensive metabolic investigations, had blood samples taken for determination of PAI-1 activity. Insulin sensitivity was determined by the euglycemic hyperinsulinemic clamp. In multivariate correlation and regression analyses, insulin sensitivity was a statistically significant determinant of PAI-1 activity (partial r=-.12; P<.001), independent of sTG, body mass index, waist-hip ratio, and other potential confounders. The levels of sTG were also independently related to PAI-1 activity (partial r=.18; P<.001). The relationships between PAI-1 and insulin sensitivity and sTG were independent of fasting glucose levels. Aggregation of risk factors of the insulin resistance syndrome was associated with increased activity of PAI-1 in men with normal glucose tolerance. We conclude that PAI-1 activity is related to insulin sensitivity and sTG, independently of each other and of other potential confounders, and that increased levels of PAI-1 should be regarded as a component of the insulin resistance syndrome.

Aged↗
PubMed1998

Relation between plasma tumor necrosis factor-alpha and insulin sensitivity in elderly men with non-insulin-dependent diabetes mellitus.

Human obesity is associated with an increased tumor necrosis factor-alpha (TNF-alpha) mRNA expression in adipose tissue. TNF-alpha decreases insulin-dependent glucose uptake by inhibiting autophosphorylation of the insulin receptor, suggesting that TNF-alpha may play a role in insulin resistance. In this study, we analyzed plasma levels of TNF-alpha in 40 70-year-old men with newly detected non-insulin-dependent diabetes mellitus and in 20 age-matched controls. Twenty of the patients had a moderate level of insulin resistance and 20 were severely insulin resistant. The plasma levels of TNF-alpha were higher in patients (4.00+/-1.53 pg/mL in moderately insulin resistant and 4.91+/-1.43 pg/mL in severely insulin resistant subjects) than in controls (3.27+/-0.79 pg/mL, P<0.001). TNF-alpha was significantly related to body mass index, fasting glucose levels, and serum triglyceride levels and inversely related to the high density lipoprotein cholesterol level. The finding of an association between high plasma levels of TNF-alpha and several metabolic abnormalities characteristic for the insulin resistance syndrome suggests that TNF-alpha may be involved in the pathogenesis of non-insulin-dependent diabetes mellitus.

Aged↗
PubMed1998

Hypertension is related to cognitive impairment: a 20-year follow-up of 999 men.

Recent findings of a linkage between high blood pressure (BP) and later development of dementia have given new prospects on cerebral target-organ damage in hypertension and have added substance to the concept of "preventable senility." The aim of this study was to analyze the impact of hypertension, circadian BP profile, and disturbed glucose metabolism on cognitive function. The study population consisted of 999 seventy-year-old men from a population-based cohort study in Uppsala, Sweden, followed with respect to cardiovascular risk factors since the age of 50 years. At the age of 70, 24-hour ambulatory BP was monitored together with measurements of insulin sensitivity, glucose tolerance, serum lipids, and lipoproteins. Cognitive function was assessed by the Mini-Mental State Examination and the Trail-Making Test. High diastolic BP at baseline predicted later impaired cognitive performance, even after excluding men with a previous stroke (n = 70). Cross-sectional measurements at age 70 showed that high 24-hour BP, nondipping, insulin resistance, and diabetes all were related to low cognitive function. The relationships between hypertension and cognitive impairment were strongest in untreated men. These data from a general population of healthy elderly men indicate that hypertension and associated metabolic disturbances might be susceptibility factors for cognitive disorders. The findings add support to possibilities of intervention in early stages in cognitive decline, ie, before manifest dementia.

Aged↗
PubMed1998

Atrial fibrillation is an independent determinant of low cognitive function: a cross-sectional study in elderly men.

BACKGROUND AND PURPOSE: Cerebrovascular disease is increasingly recognized as a cause of dementia and cognitive decline. We have previously reported an association between hypertension and diabetes and low cognitive function in the elderly. Atrial fibrillation is another main risk factor for cerebrovascular disease. The aim of this study was to investigate whether atrial fibrillation is associated with low cognitive function in elderly men with and without previous manifest stroke. METHODS: This was a cross-sectional study based on a cohort of 952 community-living men, aged 69 to 75 years, in Uppsala, Sweden. Cognitive functions were assessed by the Mini-Mental State Examination and the Trail Making Tests, and a composite z score was calculated. The relation between atrial fibrillation and cognitive z score was analyzed, with stroke and other vascular risk factors taken into account. RESULTS: All analyses were adjusted for age, education, and occupational level. Men with atrial fibrillation (n=44) had lower mean adjusted cognitive z scores (-0.26+/-0.11) than men without atrial fibrillation (+0.14+/-0.03; P=0.0003). The exclusion of stroke patients did not alter this relationship; the mean cognitive z score was -0.24+/-0.12 in the 36 men with atrial fibrillation and +0.17+/-0.03 in those without atrial fibrillation (P=0.0004), corresponding to a difference of 0.4 SDs between groups. Adjustments for 24-hour diastolic blood pressure and heart rate, diabetes, and ejection fraction did not change this relationship. Men with atrial fibrillation who were treated with digoxin (n=27) performed markedly better (-0.05+/-0.21) than those without treatment (n=9; -1.14+/-0.34; adjusted P=0.0005). Previous myocardial infarction was not associated with impaired cognitive results. CONCLUSIONS: In these community-living elderly men, we found an association between atrial fibrillation and low cognitive function independent of stroke, high blood pressure, and diabetes. Interventional studies are needed to answer the question of whether optimal treatment of atrial fibrillation may prevent or postpone cognitive decline and dementia.

Aged↗
PubMed1998

High prevalence of polycystic ovaries and associated clinical, endocrine, and metabolic features in women with previous gestational diabetes mellitus.

The prevalence of polycystic ovaries, according to ultrasonography, and associated clinical, endocrine, and metabolic features were investigated in women with previous gestational diabetes mellitus (GDM). Thirty-four women with GDM 3-5 yr before the investigation and 36 controls with uncomplicated pregnancies, selected for similar age, parity, and date of delivery, were investigated. The women with previous GDM showed a higher prevalence of polycystic ovaries [14 of 34 (41%) vs. 1 of 36 (3%); P < 0.0001], hirsutism (P < 0.01), irregular menstrual cycles (P < 0.01), and a higher body mass index (BMI; P < 0.001) than the controls. Five women (15%) with previous GDM had developed manifest diabetes (excluded in comparisons of metabolic variables). After dividing the women with previous GDM into subgroups according to ovarian appearance, the 2 subgroups showed similar glucose tolerance and prevalence of diabetes, whereas the women with polycystic ovaries were younger (mean +/- SD, 33.3 +/- 1.4 vs. 38.2 +/- 1.1; P < 0.01), had higher truncal-abdominal/femoral fat ratio according to skin folds (P < 0.05), had higher concentrations of androstenedione (P < 0.01) and testosterone (P < 0.01), and had a higher LH/FSH ratio (P < 0.01), lower levels of GH (P < 0.01), higher levels of triglycerides (P < 0.05) and cholesterol (P < 0.05) in very low density lipoprotein, all independent of age and BMI, and had a higher prevalence of pregnancy-induced hypertension (50% vs. 15%; P < 0.05) during the index pregnancy compared with the women with normal ovaries. The group of women with GDM showed a lower early insulin release after glucose (i.v. glucose tolerance test) for their degree of insulin resistance (euglycemic hyperinsulinemic clamp) compared with controls (P < 0.05). In the two subgroups, insulin sensitivity was lower in the polycystic ovaries group, independent of BMI (P < 0.05), than in the group with normal ovaries. In conclusion, ultrasonographic, clinical and endocrine signs of polycystic ovary syndrome were much increased in women with a history of GDM. Compared with the women with normal ovaries and previous GDM, those with polycystic ovaries formed a distinct subgroup that may be more prone to develop various features of the insulin resistance syndrome. Both groups showed a similarly disturbed balance between beta-cell activity and insulin sensitivity, but in women with polycystic ovaries, insulin resistance may be the dominant component.

Adult↗
PubMed1998

Effect of physiological hyperinsulinemia on blood flow and interstitial glucose concentration in human skeletal muscle and adipose tissue studied by microdialysis.

The effect of an euglycemic-hyperinsulinemic glucose clamp (94 +/- 5 microU/ml) on blood flow and glucose extraction fraction in human skeletal muscle and adipose tissue was investigated. Limb blood flow was measured by venous occlusion pletysmography and tissue blood flow by the microdialysis ethanol technique. Insulin infusion resulted in an increased blood flow in the calf and forearm (64 and 36%, respectively; P < 0.01) but not in the studied muscles of these limbs (ethanol outflow-to-inflow ratio: m. gastrocnemius 0.144 +/- 0.009 to 0.140 +/- 0.011, NS; m. brachioradialis 0.159 +/- 0.025 to 0.168 +/- 0.027, NS). This was accompanied by an increased extraction fraction of glucose, as measured by an increased arteriovenous difference over the forearm (0.16 +/- 0.04 to 0.70 +/- 0.10 mmol/l; P < 0.001) and by an increase in the estimated arterial-interstitial glucose difference in the gastrocnemius (0.82-1.42 mmol/l) and brachioradialis muscle (0.82-1.97 mmol/l). The blood flow in adipose tissue was significantly increased during insulin infusion, as evidenced by a decreased ethanol outflow-to-inflow ratio (0.369 +/- 0.048 to 0.325 +/- 0.046; P < 0.01). This was accompanied by an unchanged concentration of glucose in the dialysate (-2.6%, NS). In summary, during physiological hyperinsulinemia 1) a blood flow increase was detected in the calf and forearm, but not in the studied muscles of these limbs; 2) the blood flow increased in the subcutaneous adipose tissue; and 3) the estimated arterial-interstitial glucose difference increased in both muscles studied and was larger in the forearm muscle than the arteriovenous glucose difference over the forearm. The present study shows that microdialysis is a useful tool to obtain tissue-specific information about the effect of insulin on blood flow and glucose extraction in human skeletal muscle and adipose tissue.

Adipose Tissue↗
PubMed1998

Regression of left ventricular wall thickness during ACE-inhibitor treatment of essential hypertension is associated with an increase in insulin mediated skeletal muscle blood flow.

UNLABELLED: Left ventricular hypertrophy (LVH) has been associated with insulin resistance, a condition with an impaired insulin-mediated vasodilation in skeletal muscle. ACE-inhibitors have been reported to be superior to most other antihypertensive drugs in inducing a regression of LVH. In a double-blind study with parallel groups, 50 patients with essential hypertension were randomized to treatment with either fosinopril (20 mg o.d.) or atenolol (50 mg o.d.) for 12-16 weeks. Left ventricle wall thickness (LVWT, defined as the sum of interventricular septum and posterior wall), diastolic function (represented by the ratio between the E-wave and the A-wave of mitral blood flow) and femoral artery blood flow (FBF) were evaluated using ultrasonic measurements. FBF was measured at normoinsulinemia and after 2 h of euglycemic hyperinsulinemia. Before treatment, the insulin-induced increase in FBF was inversely related to the LVWT (r = -0.52, p < 0.02). The reduction in ambulatory 24-h SBP/DBP was 13/9 mmHg for fosinopril and 15/14 for atenolol, ambulatory DBP being significantly more reduced by atenolol (p = 0.03 for difference in treatment effect). However, only fosinopril treatment resulted in a significant reduction in LVWT (from 20.5 mm to 19.4 mm, p < 0.05). The degree of reduction in LVWT was related to the increase in FBF in the fosinopril group (r = -0.45, p < 0.05). For fosinopril (but not for atenolol), there was a positive relationship between the change in E/A ratio and the change in femoral artery stroke volume (r = 0.80, p < 0.01). CONCLUSION: Impaired insulin-induced stimulation of leg blood flow was related to an increased LVWT. Furthermore, during fosinopril treatment, regression of LVWT was associated with enhanced skeletal muscle blood flow during hyperinsulinemia. This indicates that impaired peripheral blood flow (and thereby increased afterload) may be a possible mechanism explaining the previously found association between insulin resistance and cardiovascular hypertrophy.

Adolescent↗
PubMed1997

Familial lipoprotein lipase (LPL) deficiency: a catalogue of LPL gene mutations identified in 20 patients from the UK, Sweden, and Italy.

The aim of this study was to identify mutations in the lipoprotein lipase (LPL) gene in 20 unrelated patients with familial lipoprotein deficiency (FLLD) and to investigate the genotype/phenotype relationship. The previously reported G188E mutation (Monsalve et al., J Clin Invest 86:728-734, 1990) was screened for and found to be present in seven individuals (12/40 alleles). In addition, three patients were heterozygous for the 2.0 kb insertion (Langlois et al., Proc Nalt Acad Sci US 86:948-952, 1989). Two approaches were taken for new mutation detection; single-strand conformation polymorphism and sequencing to identify micro-mutations in the proximal promoter and exons 1-9 of the LPL gene and Southern blotting to identify gross mutations. Ten different point mutations were found (W86G, A158T, H183Q, G188E, S193R, P207L, L252X, N291S, M301T, L303P). Additionally, a two nucleotide deletion in exon 6 (delta1006-1007), a six nucleotide deletion in exon 8 (delta1441-1447), and a silent substitution in the wobble position of codon E118 were identified. In vitro mutagenesis and expression in COS-B cells suggested that the A158T and S193R substitutions virtually abolished enzyme activity. In analysing the genotype/phenotype relationship, there was no strong association between age at diagnosis, severity of symptoms, lipid levels, and the nature/position of the mutation. Triglyceride levels, however, were higher in compound heterozygotes compared to true homozygotes, possibly reflecting increased instability of heterodimers. Overall, 29 of 40 (72.5%) mutant alleles were identified. Failure to identify the mutation in 11 alleles might reflect the inadequacy of the method or the possibility that mutations lie within regions of the gene not screened in the study because of lack of availability of sequence.

Adult↗
PubMed1997

Studies of the genetic variability of the coding region of the hepatocyte nuclear factor-4alpha in Caucasians with maturity onset NIDDM.

Mutations in the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene cause the type 1 form of maturity onset diabetes of the young (MODY1). To address the question of whether genetic variability of HNF-4alpha is associated with late onset non-insulin-dependent diabetes mellitus (NIDDM) we have sequenced the coding region and intron/exon boundaries of the gene in 36 randomly recruited Danish NIDDM patients. Two nucleotide substitutions that changed the sequence of HNF-4alpha were identified: Thr/Ile130, which has been reported previously and a novel Val/Met255. The Val/Met 255 mutation was found in 4 of 477 Danish NIDDM patients and in none of 217 glucose tolerant control subjects; thus it cannot be excluded that this mutation may have an impact on NIDDM susceptibility. Among 509 NIDDM patients the allelic frequency of the Thr/Ile130 variant was 4.7% (95% confidence interval: 3.4-6.0%) compared to 1.9% (0.7-3.1%) among 239 control subjects (p = 0.008). However, in a population sample of 942 Swedish men with an average age of 70 years the allelic frequency of the variant was similar in 246 men with either impaired glucose tolerance (5.6% [2.6-8.6%]) or NIDDM (5.4% [2.7-8.1%]) as compared to 666 glucose tolerant men (5.1% [3.9-6.3%]). Also in a population sample of 369 young healthy Danes the prevalence of the codon 130 variant (4.7% [3.2-6.2%]) was similar to what was found in Swedish Caucasians. Thus, the allelic frequency of the Thr/Ile130 variant among the control subjects in the Danish case-control study deviates from the prevalence in the two other studies which is why we consider the significant association between the codon 130 variant and NIDDM an incidental finding. In glucose tolerant subjects the codon 130 variant in its heterozygous form had no major effect on glucose-induced insulin and C-peptide release although a tendency to a lower insulin secretion during an oral glucose tolerance test was seen in middle-aged subjects. In conclusion, variability in the coding region of the HNF-4alpha gene is not a common cause of NIDDM among whites of Danish ancestry. However, a Val/Met255 mutation was found exclusively in NIDDM patients (0.8% of cases) and functional as well as family segregation studies are needed to determine whether this HNF-4alpha variant is a NIDDM causing mutation.

Aged↗
PubMed1997

Metabolic effects of carvedilol in hypertensive patients.

OBJECTIVE: Fifty-six patients with essential hypertension were recruited to study the metabolic effects of carvedilol, a non-selective beta-adrenoceptor-blocker with alpha 1-adrenoceptor blocking properties. METHODS: The study started with a single-blind, 4-6-week placebo-treatment period followed by an open 6-month active treatment period. There was an option to increase the dose from 25 mg carvedilol to 50 mg daily after 6 weeks. Metabolic investigations were carried out at the end of the placebo period and at the end of the active treatment period. RESULTS: The results show that during carvedilol treatment blood pressure was efficiently lowered. The increase in very low density lipoprotein triglyceride concentration was 13%. Despite this modest increase high density lipoprotein cholesterol was reduced by 11%. The metabolic clearance rate of glucose at the hyper-insulinemic clamp test (adjusted for the prevailing insulin and glucose concentrations) decreased by 17%. At the i.v. glucose tolerance test the insulin area under the curve was increased by 18% and the glucose area by 10%. CONCLUSION: The alpha 1-adrenoceptor-blocking characteristics of carvedilol probably explain the moderate changes of lipoprotein concentrations and insulin sensitivity gained compared with what is usually obtained with a non-selective beta-adrenoceptor-blocker.

Adrenergic alpha-Antagonists↗
PubMed1997

Serum calcium: a new, independent, prospective risk factor for myocardial infarction in middle-aged men followed for 18 years.

BACKGROUND: Primary hyperparathyroidism (HPT) is a disease characterized by hypercalcemia, and associated with an increased mortality in cardiovascular diseases. However, serum calcium levels within the normal range have not been evaluated as a prospective cardiovascular risk factor. METHODS: A cohort of males aged 50 (n = 2183) were investigated in 1970-1973 for serum calcium and known cardiovascular risk factors. They were then followed up over the next 18 years. RESULTS: During the follow-up period, 180 subjects experienced a myocardial infarction (MI). The serum calcium levels were significantly elevated at the baseline (2.37 +/- 0.09 SD versus 2.35 +/- 0.09 mmol/l, p < 0.03) in the subjects who developed a MI when compared with the rest of the cohort. Also blood pressure, body mass index (BMI), fasting insulin, serum cholesterol, serum triglycerides, and the atherogenic index were significantly elevated in the MI group (p < 0.01), while HDL-cholesterol was lower at the baseline investigation (p < 0.01). Cox's proportional hazard analysis showed that only serum calcium (p < 0.01), BMI (p < 0.0003), diastolic blood pressure (p < 0.0009), and the atherogenic index (p < 0.002) were significantly independent risk factors for MI. The range of serum calcium levels from the mean value, -2 SDs to the mean value +2 SDs corresponds to a variation in estimated risk for MI ranging from 0.06 to 0.15. CONCLUSIONS: Serum calcium was found to be an independent, prospective risk factor for MI in middle-aged males suggesting a role for extracellular calcium levels in the atherosclerotic process.

Calcium↗
PubMed1997

The alterations in insulin sensitivity during angiotensin converting enzyme inhibitor treatment are related to changes in the calcium/magnesium balance.

The present analysis was undertaken to investigate the relations between alterations in mineral factors, especially the balance between serum calcium and magnesium concentrations (S-Ca and S-Mg, respectively), and variables reflecting glucose and lipid metabolism during angiotensin converting enzyme (ACE) inhibitor treatment. A total of 96 patients with essential hypertension, participating in four double-blind studies with four different ACE inhibitors and similar protocols, were included. At the end of the initial placebo period and at the end of the period of active drug treatment, a hyperinsulinemic euglycemic clamp test was carried out, lipoprotein status was assessed, and the concentrations of serum electrolytes were measured. The serum ACE activity was determined in the group treated with fosinopril. Changes in insulin sensitivity index (M/I) were directly correlated to alterations in S-Mg (r = 0.24, P < .02), and inversely correlated to changes in S-Ca (r = -0.19, P = .07) and the ratio between serum calcium and magnesium concentrations (Ca/Mg) (r = -0.27, P < .008). The change in total serum triglycerides (S-Tg) was inversely correlated to the change in S-Mg (r = -0.35, P < .0005), and directly correlated to the change in Ca/Mg ratio (r = 0.36, P < .0004). The reduction in serum ACE activity correlated to a more pronounced increase in S-Mg r = -0.62, P < .002), and decrease in the Ca/Mg ratio (r = 0.73, P = .0002). We conclude that the changes in the studied metabolic variables and serum ACE activity during ACE inhibitor treatment are related to alterations in mineral status and the balance between calcium and magnesium concentrations in serum.

Adolescent↗