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Biomedical subjects

H Lithell

Publications and source records attributed to H Lithell.

At least 199 records · Page 11Linked to original sources
PubMed1989

C-peptide but not insulin concentrations are related to the serum lipoprotein levels during insulin treatment of non-insulin-dependent diabetes mellitus (NIDDM) patients.

In 21 non-insulin-dependent diabetic patients with secondary drug failure, once-daily long-acting insulin lead to a moderately improved metabolic control. At the conclusion of the study (eight months) the fasting blood glucose and HbA1c concentrations were significantly decreased, but the postprandial blood glucose concentrations in the afternoon were unaltered. The peripheral insulin sensitivity, as measured by the intravenous insulin tolerance test, and the lipoprotein lipase activity in adipose and skeletal muscle tissue had increased. After initiation of insulin therapy there was a transient decrease of the fasting and glucagon-stimulated C-peptide concentrations. The very low density lipoprotein lipids and apolipoprotein B, A-I and A-II were also reduced transiently. The only significant difference in lipoprotein composition at eight months compared with on admission, was an increased cholesterol and decreased triglyceride concentration in the high density lipoproteins. There were significant relationships between the C-peptide, but not the peripheral insulin, concentrations and the serum lipid concentrations. This may indicate that high peripheral insulin concentrations after administration of exogenous insulin may affect the hepatic lipoprotein production less than the portal insulin concentrations mainly derived from endogenous production.

Biomarkers↗
PubMed1988

Relation of serum calcium concentration to metabolic risk factors for cardiovascular disease.

Data from a health screening survey with over 18,000 adult participants were used to determine the relations between serum calcium concentration and the cardiovascular risk factors hypertension, hyperglycaemia, and hyperlipidaemia. Blood pressure and serum glucose and cholesterol concentrations were all positively related to each other independent of age, sex, kidney function, and obesity. Similar relations between the risk factors were found in subjects with hypertension or hyperglycaemia independent of the degree of overweight. These results suggested that there might be a metabolic syndrome of cardiovascular risk factors. Serum calcium concentration was positively related to systolic and diastolic blood pressures and serum glucose and cholesterol concentrations. Thus a common feature in the syndrome is an increased serum calcium concentration. The relations between serum calcium concentrations and the cardiovascular risk factors were not limited to the upper parts of the distribution, being seen over a wide range. Changes in calcium metabolism seem to be related to a metabolic syndrome of hypertension, impaired glucose tolerance, and hyperlipidaemia.

Aged↗
PubMed1988

Characterisation of insulin-like growth factor I receptor in skeletal muscles of normal and insulin resistant subjects.

The insulin-like growth factor I receptor and the activity of its associated tyrosine kinase activity were characterised in wheat germ agglutinin extracts from skeletal muscle biopsies from nine control and ten obese Type 2 (non-insulin-dependent) diabetic subjects, who had marked peripheral in vivo insulin resistance for glucose disposal and hyperinsulinaemia. In parallel studies, the concentration of the insulin receptor and its tyrosine kinase activity were examined in the biopsy extracts and compared to the findings for the insulin-like growth factor I receptor system. Specific binding sites for insulin-like growth factor I were detected. The receptor binding of insulin-like growth factor I was not changed in the obese diabetic subjects as compared to binding activity in the biopsies from the control subjects. The molecular weight of the insulin-like growth factor I receptor alpha subunit was similar in both groups (135 kDa). The insulin-like growth factor I stimulated tyrosine kinase activity was also similar for the two groups. In contrast, insulin binding activity was 30% less in the receptor extracts from the in vivo insulin resistant group when compared to the control group. Moreover, insulin-stimulated tyrosine kinase activity was reduced in the former group by 40% when the value was corrected for insulin binding. Thus, specific insulin-like growth factor I receptors are present in human skeletal muscle. These receptors are normal in insulin resistant obese Type 2 diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1988

Application of prazosin is associated with an increase of insulin sensitivity in obese patients with hypertension.

The aim of this study was to determine whether insulin sensitivity measured by the euglycaemic insulin clamp technique is lower in patients with primary hypertension than in matched healthy control subjects, and whether this sensitivity was affected after 12 weeks of antihypertensive treatment with the alpha 1-adrenoceptor blocking drug prazosin. Twelve moderately obese normoglycaemic patients (four men), with hypertension not previously treated with pharmacological agents and diastolic blood pressure above 100 mm Hg, and 12 healthy matched control subjects participated. Supine blood pressure decreased 12/5 mm Hg (p less than 0.01) and standing blood pressure 14/9 mm Hg (p = 0.001) during prazosin treatment (mean dosage 5.3 +/- 1.6 mg/day (SD]. During euglycaemic insulin clamp studies the control subjects showed a higher mean glucose uptake than the untreated hypertensive patients (7.5 +/- 1.0 and 5.8 +/- 1.9 mg.kg b.w.-1.min-1, respectively, p less than 0.01). During prazosin treatment there was no significant difference between the hypertensive patients and the control subjects in this respect (6.6 +/- 2.8 and 7.5 +/- 1.0, respectively, p = 0.21). During prazosin treatment, however, the disappearance rate of glucose decreased during the intravenous glucose tolerance test (from 1.7 +/- 0.9 to 1.3 +/- 0.6, p less than 0.02) and the area under the glucose concentration-time curve decreased by 38% (from 473 +/- 119 to 294 +/- 99, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1988

Impaired glucose handling in active rheumatoid arthritis: relationship to peripheral insulin resistance.

Glucose metabolism was studied after an intravenous glucose loading in normal-weighted, previously untreated patients (n = 14) with active rheumatoid arthritis (RA). The patients displayed an enhanced insulin response and impaired glucose handling compared with healthy controls (P less than .001). The insulin sensitivity, measured as the glucose utilization rate during steady state of euglycemia (M) was significantly decreased (P less than .01) among the patients compared to the controls (5.5 +/- 1.9 mg/kg BW/min [mean +/- SD] and 7.2 +/- 1.2, respectively). The corresponding values for the metabolic clearance rate (MCR) were 5.8 +/- 0.6 mL/kg BW/min and 8.2 +/- 0.4, respectively (P less than .01). In the patient group the k value correlated with the peripheral insulin sensitivity (P less than .01), which, in turn, was inversely related to the acute phase reaction (P less than .05). During 1 week of potent anti-inflammatory treatment with corticosteroids (prednisolone 20 mg daily) the k value improved P less than .001), the insulin sensitivity tended to improve and the insulin response increased (P less than .001) after an intravenous glucose loading. Five patients who had a remission of their disease on sulphasalazine as antirheumatic therapy were reexamined. A normalization of the inflammatory activity as well as the glucose handling and insulin sensitivity was achieved. The data obtained indicate that impaired glucose handling in active RA is related to insulin resistance. The linkage between inflammatory indices and glucose metabolism might reflect a special consequence of inflammation, but the influence of nonspecific disease manifestations, ie, malnutrition, inactivity, and myopenia, has to be considered.

Adrenal Cortex Hormones↗
PubMed1988

Changes in calcium metabolic indices during long-term treatment of patients with essential hypertension.

1. Disturbances of calcium metabolism, mimicking mild, compensated secondary hyperparathyroidism, accompany essential hypertension, but it is not known whether these alterations are primary or only secondary to the elevated blood pressure. 2. Indices of systemic calcium metabolism were followed prospectively during 6 months' treatment with either propranolol, bendroflumethiazide or verapamil in 35 patients with essential hypertension. Multivariate statistical methods were employed to study the effects of blood pressure reduction upon the metabolic indices with adjustment for the effects of the different antihypertensive agents. 3. Propranolol treatment increased the plasma ionized calcium and serum phosphate concentrations, and reduced the serum levels of parathyroid hormone, free fatty acids and glycerol. Neither the total nor the total albumin-modified serum calcium concentration was significantly affected. Thus, presumably the decrease in free fatty acids reduced the calcium complex and the calcium binding to albumin, and consequently increased the plasma ionized calcium, thereby suppressing the secretion of parathyroid hormone. 4. Bendroflumethiazide caused a reduction of the fasting renal calcium excretion to half the pretreatment level, but produced no other significant changes in the various indices of calcium metabolism. 5. During verapamil treatment, the fasting renal excretion of calcium and magnesium increased, whereas the free fatty acids and glycerol concentrations in serum were reduced. These two changes presumably balanced each other, as the plasma ionized calcium and serum parathyroid hormone concentrations were not significantly altered. 6. There were no consistent relationships between the decrease in blood pressure and the changes in the metabolic indices, either in the total sample or within any subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

A pilot study of metabolic effects of intravenously given alpha-calcidol in patients with chronic renal failure.

Disturbances of calcium homeostasis might be involved in the pathogenesis of the metabolic derangements associated with uraemia. Indices of glucose and lipoprotein metabolism as well as blood pressure were measured in nine patients with chronic renal failure who were on regular hemodialysis. Seven of them thereafter received alpha-calcidol (a synthetic analogue to active vitamin D) intravenously for three months. Prior to therapy the patients had, compared with age and sex matched controls, impaired glucose tolerance, hyperlipoporteinemia and raised blood pressure. Treatment with alpha-calcidol reduced elevated serum levels of parathyroid hormone (PTH). Concomitantly there was a reduction of fasting blood glucose and HbA1C (glycosylated hemoglobin) concentrations and an improvement of the glucose tolerance, whereas insulin concentrations were unaffected. There was a reduction of whole serum triglycerides and an increase of HDL cholesterol. A significant decrease was also observed for systolic blood pressure. This pilot study suggests that treatment with active vitamin D, probably through its effects on calcium metabolism, is beneficial with regard to the metabolic disturbances in uraemia.

Blood Glucose↗
PubMed1988

Reduction of blood pressure by treatment with alphacalcidol. A double-blind, placebo-controlled study in subjects with impaired glucose tolerance.

Disturbances of calcium or vitamin D metabolism have been suggested to be of pathogenetic importance both for hypertension and impaired glucose tolerance, two disorders that are commonly associated. In the present study 65 men, aged 61-65 years, with impaired glucose tolerance were enrolled in a prospective, double-blind, placebo-controlled study over 12 weeks evaluating the effects of 0.75 microgram alphacalcidol, a synthetic analog to the active metabolite of vitamin D. In the 26 patients with blood pressure greater than or equal to 150/90 mmHg before treatment a significant reduction (p less than 0.01) of both the systolic (SBP) and diastolic (DBP) blood pressure was found after therapy (from 171/95 to 150/88 mmHg). The effect was additive to concomitant antihypertensive treatment and was correlated (p = 0.03) to a reduction of serum levels of parathyroid hormone. Also in the whole group of patients given alphacalcidol blood pressure was moderately lowered from a mean of 152/87 +/- 22/10 (SD) to 143/84 +/- 17/8 mmHg. There were no relationships between the changes in body weight, blood glucose or insulin parameters and the changes in blood pressure during the trial. The findings are compatible with the concept that calcium metabolism influences blood pressure regulation and suggest that supplementation with a physiologic dose of active vitamin D could be beneficial for patients with high blood pressure.

Aged↗
PubMed1988

Are effects of antihypertensive treatment on lipoproteins merely "side-effects"? A comparison of prazosin and metoprolol.

Thirty-seven patients with a supine systolic blood pressure greater than 160 and/or a diastolic blood pressure greater than 95 mmHg were enrolled in the study and treated for 6 months with prazosin and 6 months with metoprolol (in random order). Neither the systolic nor the diastolic blood pressures differed after the two types of treatment (median difference 0/0 mmHg). The mean and median differences in serum cholesterol, however, were 0.4 and 0.3 mmol/l respectively, which were 9 and 5% of the pretreatment values. The corresponding differences in the atherogenic index (in which cholesterol in high density lipoproteins is integrated) were 10 and 8% of the pretreatment values. This difference in the metabolic response to the two drugs at the same blood pressure level is most probably of importance in the long-term prevention of ischaemic heart disease, for which high levels of serum cholesterol and atherogenic index are major risk factors.

Clinical Trials as Topic↗
PubMed1987

Alcohol intemperance and sudden death.

Ten years after a health screening examination was offered to 50 year old men 32 of the 2322 participants and 12 of the 454 nonparticipants had died of ischaemic heart disease. Of these, 26 and 11 respectively had suffered sudden death, for which necropsy was performed. Half of the men who had died suddenly had been registered for alcohol intemperance up to 1973, which was four times the prevalence of such registrations in the general population. Registration at both the Swedish Temperance Board and the Bureau of Social Services was associated with an odds ratio of 3.74 for sudden death as compared with not being registered at either. Logistic analysis including the classical risk factors for ischaemic heart disease together with registration for alcohol intemperance and at the Bureau of Social Services showed only the two types of registration and systolic blood pressure to be independent risk factors. On the other hand, there was no overrepresentation of subjects entered in the registers among those surviving a myocardial infarction. For non-fatal myocardial infarction blood pressure and serum triglyceride concentration were significant risk factors and serum cholesterol concentration, smoking, and body mass index probable risk factors; the two types of registration were not independent risk factors. Alcohol intemperance is strongly associated with an increased risk of sudden death after myocardial infarction.

Alcoholism↗
PubMed1987

Defective insulin receptor tyrosine kinase in human skeletal muscle in obesity and type 2 (non-insulin-dependent) diabetes mellitus.

The tyrosine kinase activity of the insulin receptor was investigated in skeletal muscle biopsies from insulin-resistant males with obesity or with Type 2 (non-insulin-dependent) diabetic males who were lean or overweight. The kinase activity of the receptor from all three groups of insulin-resistant subjects was 40% less when compared to the activity of lean control subjects. This alteration was present in the absence of changes in the level of the insulin receptor on its insulin binding characteristics. We conclude that the tyrosine kinase activity of the skeletal muscle insulin receptor is defective in obesity and Type 2 diabetes, and that this alteration contributes to the insulin-resistant characteristics of both disorders.

Aged↗
PubMed1987

Physical training as treatment for type 2 (non-insulin-dependent) diabetes in elderly men. A feasibility study over 2 years.

At a health examination of men approximately 60 years old, 48 were found to have Type 2 (non-insulin-dependent) diabetes. All had been healthy 10 years earlier. The intention was to randomly allocate those with mild diabetes to a training or a control group and study the long-term influence of regular training on the progress of the disease. However, it was found that the majority--39 of 48--had other diseases or were on treatment which made regular training difficult and would have complicated the interpretation of the metabolic effects of training. Eight men took part in a physical training programme for up to 2 years. Aerobic capacity, glucose tolerance and serum lipoproteins were measured before and at the end of the training period. Another group of eight men with Type 2 diabetes, of similar weight, age and relative aerobic capacity, who did not undergo the physical training, served as control subjects. The oxygen uptake increased by 16% in the training group and decreased by 12% in the control group but no significant changes could be demonstrated in body weight, fasting blood glucose, serum lipoproteins, glucose tolerance or insulin values at a 75-g oral glucose tolerance test between the two groups. Two patients in the training group developed coronary heart disease, two deteriorated metabolically (drug treatment had to be added), and there were two drop-outs. The results cast doubts on the feasibility and efficacy of physical training as a long-term treatment for the majority of Type 2 diabetic patients, who are older than 60 years.

Diabetes Mellitus, Type 2↗
PubMed1987

Efficacy and safety of bisoprolol and atenolol in patients with mild to moderate hypertension: a double-blind, parallel group international multicentre study.

Three hundred and fifteen patients were randomly allocated to treatment for six months with bisoprolol 5 or 10 mg day-1 or atenolol, 50 mg day-1, in a double-blind, double-dummy parallel group, international multicentre study. Two hundred and ninety-two (175 men and 117 women) were eligible for statistical follow-up. Their mean age was 52.6 years (range 28-70). All patients had a supine diastolic blood pressure of 95-120 mmHg on two occasions during the four weeks of placebo treatment. Twenty-four patients ended the study prematurely and a further 19 had their regimes changed because of an insufficient effect. The reasons for drop-out were similar in the three treatment groups. Thus, 249 patients continued to receive the treatment they were allocated to, with 80, 83 and 86 patients in the three respective groups. The sex and age distributions and the number of previously treated hypertensives were similar in the three groups. At the end of placebo treatment the supine blood pressures in the three groups (bisoprolol 5 or 10 mg day-1 or atenolol 50 mg day-1, respectively) were 163.9/102.5, 157.4/101.8 and 160.0/102.2 mmHg, respectively. The systolic blood pressure was higher (P less than 0.05) in the group receiving bisoprolol 5 mg day-1 than in the 10 mg day-1 group. After 26 weeks of treatment the supine blood pressures in the three groups were 150.6/90.8, 142.0/89.1 and 148.6/91.7 mmHg, respectively. The largest estimated difference in blood pressure reduction was 4.6/2.3 mmHg between the group receiving bisoprolol 10 mg day-1 and the group receiving atenolol 50 mg day-1. A reduction in mean blood pressure of greater than or equal to 10 mmHg was noted in 66% of the patients in the bisoprolol group (10 mg day-1), in the other groups 66 and 59%, n.s. Bisoprolol is effective, well-tolerated and safe in the treatment of hypertension. A daily dose of 5 mg seems recommendable for the majority of hypertensive patients and seems equipotent with 50 mg day-1 of atenolol in the present study.

Adult↗
PubMed1987

Treatment with one-alpha-hydroxycholecalciferol in middle-aged men with impaired glucose tolerance--a prospective randomized double-blind study.

Experimental evidence suggests a specific role for the active metabolite of vitamin D (1,25(OH)2D3) in insulin secretion. In order to evaluate the possible clinical significance, 65 middle-aged men with impaired glucose tolerance, and normal serum levels of vitamin D metabolites, were enrolled in a three-month study where they were given either 0.75 micrograms alpha-calcidol (1 alpha(OH)D3) daily or placebo. Indices of glucose and lipid metabolism were evaluated before and after treatment. There were no significant changes during the trial neither for fasting blood glucose, hemoglobin A1c or for the intravenous glucose tolerance between the treatment and the placebo groups, nor were there any consistent changes in insulin values during the glucose tolerance test. Subjects treated with alpha-calcidol displayed a significant reduction in body weight with an average of 1.1 kg, while those receiving placebo lost no weight. Treatment did not affect the serum lipoprotein values. Thus, a modest dose of active vitamin D, which did not cause elevation of serum calcium, did not provide general improvement of glucose tolerance or of insulin secretion when given to patients with impaired glucose tolerance, but without vitamin D deficiency, over a three-month period.

Aged↗
PubMed1987

Prevalence of renal stones in 60-year-old men. A 10-year follow-up study of a health survey.

Information on the occurrence of renal stones was obtained in a health survey of 50-year-old men and at follow-up of the same group 10 years later. At the latter investigation, 338 of 1781 participants (19%) had a history of renal stone formation. In 47% there had been recurrences. For the individual there was a continuous risk of acquiring a first renal stone up to the age of 60. Approximately 0.5% of the entire unselected population experienced onset annually up to this age. Recurrent renal stones occurred primarily in those with a positive family history of stones or early onset of stones, as well as in those who previously had frequently formed stones. A carefully obtained clinical history should be useful in predicting recurrences in the individual stone former.

Follow-Up Studies↗
PubMed1987

Lipoprotein lipase activity and intramuscular triglyceride stores after long-term high-fat and high-carbohydrate diets in physically trained men.

Men with regular physical training habits voluntarily increased their dietary fat intake from 43 to 54% of energy (E%) for four weeks. This was followed by a low-fat (29 E%), high-carbohydrate diet for another four weeks. During the high-fat diet period, the muscle lipoprotein lipase activity (LPLA) increased from 59 +/- 8 to 106 +/- 12 mU/g (mean +/- SE) (P less than 0.05). After the high-carbohydrate diet, LPLA was 57 +/- 16 mU/g, and unchanged relative to the pre-trial value. The triglyceride content in m. vastus lateralis increased from 30 +/- 4 to 47 +/- 9 mmol/kg d.w. (P less than 0.05; mean +/- SE) following the high-fat diet and to 41 +/- 8 following the high-carbohydrate diet. Neither of the diets affected the serum triglyceride and insulin concentrations, nor glucose, glycerol, beta-hydroxybutyrate, citrate and lactate levels in the blood. Nor did they alter enzyme activities in muscle used as markers for the oxidative (citrate synthase, beta-hydroxy-acyl CoA dehydrogenase) and glycolytic (glyceraldehyde phosphate dehydrogenase, lactate dehydrogenase) capacity. It is concluded that one month's adaptation to a high-fat diet results in increased muscle-LPL activity indicating a higher capacity for uptake of fatty acids from circulating serum triglycerides into the muscle cell in association with a greater capacity for triglyceride storage in the muscle. Under these conditions serum triglycerides were not decreased despite the increased muscle LPLA, and serum insulin variations could not explain the change in muscle LPLA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Insulin receptor binding and metabolic effects of insulin in human subcutaneous adipose tissue in untreated non-insulin dependent diabetes mellitus.

Insulin action at the target tissue level in non-insulin dependent diabetes mellitus was investigated using human adipose tissue. Specific adipocyte receptor binding of insulin and the effects of the hormone on glucose oxidation and lipolysis were determined in subcutaneous adipose tissue. The study included 25 patients with untreated non-insulin dependent diabetes mellitus and 38 healthy control subjects matched for age, sex and body weight. Insulin stimulated adipose tissue glucose oxidation in a dose-dependent way in the control subjects. On the other hand, a marked inhibition of this insulin effect was observed in the diabetics. A weak stimulation was observed only at high unphysiological hormone concentrations [greater than or equal to 0.7 nmol/l] and the maximal insulin response was 6 times lower than that in the control subjects. However, neither specific insulin receptor binding nor the antilipolytic effect of insulin were inhibited in diabetes. Similar results with insulin binding and the metabolic effects of insulin were obtained in non-obese normoinsulinemic diabetics as compared to moderately obese hyperinsulinemic diabetics. It is concluded that adipose tissue insulin resistance in non-insulin dependent diabetes mellitus only involves glucose metabolism and not antilipolysis. Furthermore, it may solely be due to postreceptor defects in insulin action and seems not to be influenced by obesity or oversecretion of insulin.

Adipose Tissue↗