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Biomedical subjects

C Berne

Publications and source records attributed to C Berne.

At least 37 records · Page 2Linked to original sources
PubMed2001

Sleep-disordered breathing and glucose metabolism in hypertensive men: a population-based study.

OBJECTIVES: Diabetes mellitus and obstructive sleep apnoea (OSA) are two prevalent medical problems. Both are strongly associated with obesity and hypertension. The aim of this study was to investigate whether the association between OSA and diabetes is entirely dependent on obesity in hypertensive men. DESIGN: A population-based study. SETTING: The municipality of Uppsala, Sweden. Subjects and methods. In 1994, 2668 men aged 40-79 years answered a questionnaire regarding snoring, sleep disturbances and somatic diseases. An age-stratified sample of 116 hypertensive men was selected for a whole-night sleep study. Twenty-five of them had diabetes, defined as reporting regular medical controls for diabetes or having a fasting blood glucose > or =6.1 mmol L(-1). RESULTS: The prevalence of severe OSA, defined as apnoea-hypopnoea index (AHI) > or =20 h(-1) was significantly higher in diabetic patients than in normoglycaemic subjects (36 vs. 14.5%, P < 0.05). The sample was divided into four groups based on the presence or absence of severe OSA and the presence or absence of central obesity, defined as waist-to-hip ratio (WHR) > or =1.0. In a logistic regression model with the non-OSA, WHR <1.0 as the reference group, the adjusted odds ratio (95% confidence interval) for diabetes was 11.8 (2.0-69.8) in the OSA, WHR > or =1.0 group, whilst it was 3.6 (0.9-14.8) in the non-OSA, WHR > or =1.0 group and 5.7 (0.3-112) in the OSA, WHR <1.0 group. In a linear regression model, after adjustment for WHR, there was a significant relationship between variables of sleep-disordered breathing and fasting insulin, glucose and haemoglobin A1c. CONCLUSIONS: We conclude that, in hypertensive men, although obesity is the main risk factor for diabetes, coexistent severe OSA may add to this risk. Sleep breathing disorders, independent of central obesity, may influence plasma insulin and glycaemia.

Adult↗
PubMed2001

Myocardial infarction and prevalence of diabetes mellitus. Is increased casual blood glucose at admission a reliable criterion for the diagnosis of diabetes?

AIMS: To investigate the prevalence of diabetes mellitus in patients with acute myocardial infarction and to determine whether casual blood glucose and haemoglobin A1c measured at admission could be used to diagnose diabetes mellitus. METHODS AND RESULTS: A prospective study that included all patients with acute myocardial infarction hospitalized during a one-year period at a coronary care unit. Casual blood glucose was measured at admission, fasting blood glucose during the hospital stay and, if necessary for classification, 2-3 months after discharge. Haemoglobin A1c was measured once at admission. Of 305 patients included in the study, 285 could be classified into three groups: 21% of these had previously diagnosed diabetes, 4% had newly diagnosed diabetes and the remaining patients were categorized as non-diabetic. Casual blood glucose >or=11.1 mmol x l(-1)at admission was found in 12 patients with no previously known diabetes, but diabetes mellitus was confirmed in only six of these patients. Haemoglobin A1c showed considerable overlapping of values between the three groups of patients (i.e. patients with known diabetes mellitus, patients with newly diagnosed diabetes mellitus and non-diabetics). CONCLUSION: One of four patients with acute myocardial infarction had diabetes mellitus. Increased casual blood glucose at admission was not a reliable measure to establish a diagnosis of diabetes and thus follow-up measures were necessary. Haemoglobin A1c was found to be an unreliable measure in the verification of diabetes.

Aged↗
PubMed2001

Do guidelines matter? A population-based study of diabetes drug use during 20 years.

OBJECTIVE: To analyse diabetes drug use in a defined population during 20 years in relation to recommendations in published guidelines. DESIGN: From the Tierp Study Database, all medical records for diabetes patients at the primary health care centre in Tierp municipality and all prescriptions for diabetes drugs at the local pharmacies during the period 1975-1994 were collected. Data for 2125 persons were obtained, generating 13,190 person-years of observation. SETTING: Tierp primary health care district. MAIN OUTCOME MEASURES: Diabetes treatment. RESULTS: The annual prevalence of diabetes mellitus increased from 2.8% (565 patients) to 3.8% (734 patients). When guidelines emphasised diet treatment, treatment with diet only increased and oral pharmacological treatment decreased. When guidelines emphasised better glycaemic control, diet only decreased and biguanide treatment increased, and when guidelines emphasised vigorous glycaemic control, treatment with diet only decreased further and sulphonylurea and insulin use increased. The substantial age and sex differences in antidiabetic drug use at the beginning of the period were partly reduced over time. CONCLUSIONS: The considerable changes in antidiabetic drug use during the study period coincided with changes in the guidelines issued. The age and sex differences in drug use became less pronounced towards the end of the period.

Adolescent↗
PubMed2001

In vitro and in vivo studies of a naturally occurring variant of the human p85alpha regulatory subunit of the phosphoinositide 3-kinase: inhibition of protein kinase B and relationships with type 2 diabetes, insulin secretion, glucose disappearance constant, and insulin sensitivity.

In humans, the Met326Ile missense variant of the p85alpha regulatory subunit of the phosphoinositide 3-kinase (PI3K) has been associated with either significant reductions in glucose effectiveness and intravenous glucose tolerance in Caucasians or a significantly higher insulin secretory response in Pima Indians. In the present study, we genotyped 1,190 Caucasian males to evaluate the impact in vivo of the Met326Ile variant of the p85alpha subunit of PI3K on the acute insulin response, intravenous glucose tolerance, insulin-mediated glucose uptake, and the prevalence of type 2 diabetes after 20 years of follow-up. We also expressed the variant in vitro to evaluate the impact on insulin-stimulated activation of protein kinase B (PKB). The Met326Ile variant of p85alpha was not associated with type 2 diabetes or with alterations in insulin secretion, insulin sensitivity, or intravenous glucose tolerance in vivo. Expressed in vitro, the Ile326 and the Met326 variant acted equally as a dominant-negative and prevented (60-70% inhibition) insulin-mediated activation of PKB by inhibiting the phosphorylation of PKB at Thr308. We conclude that the Met326Ile variant of the p85alpha regulatory subunit of PI3K is likely to be as functionally normal in vivo as in vitro.

Aged↗
PubMed2000

Improved hemorheological properties during infusion of a lipid emulsion (Intralipid) in healthy subjects.

OBJECTIVES: Lipid emulsions are commonly used for nutrition in critically ill patients. In these patients interventions resulting in deteriorated blood rheology and thereby an impaired microcirculation may be deleterious. This study examined the acute hemorrheological effects of the lipid emulsion Intralipid. We have recently shown that hyperinsulinemia exerts a negative effect on erythrocyte deformability, and here the effect of hyperinsulinemia combined with Intralipid was studied. SUBJECTS AND INTERVENTIONS: Eleven healthy subjects received Intralipid (200 mg/ml) intravenously as a bolus injection (0.5 ml/kg) over 10 min and thereafter as a continuous intravenous infusion (90 ml/h) for 4 h combined with heparin (200 U/h) to stimulate lipolysis. During the final 2 h an euglycemic hyperinsulinemic clamp was added. Five subjects underwent the same protocol with the exception that saline was given instead of Intralipid and heparin. MEASUREMENTS AND RESULTS: Whole blood viscosity, plasma viscosity, erythrocyte aggregation tendency and fluidity were measured by rotational viscometry. Compared with basal and control values the Intralipid infusion caused greater erythrocyte fluidity (p < 0.05) and less aggregation tendency (p < 0.05). Whole blood and plasma viscosity remained unchanged. Hyperinsulinemia had no significant effect on the hemorrheological variables measured. CONCLUSIONS: Intralipid has no deleterious effects on blood rheology in healthy subjects. Instead, it leads to improved erythrocyte aggregation tendency and fluidity. If the emulsion exerts the same effects in patients with impaired circulation, the use of Intralipid may be beneficial in these patients.

Adult↗
PubMed2000

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

Men run a higher risk for cardiovascular disease than women, even if hypertensive. This has been attributed to a more pronounced central (abdominal) fat distribution in men as well as menopausal state in women. The hypothesis to be tested in hypertensives was that men have more pronounced insulin resistance and other cardiovascular risk factors than pre-menopausal, but not post-menopausal, women. We carried out a cross-sectional observation study of middle-aged hypertensives of both sexes, divided into two age groups, below or over 50 years of age. The study was performed in untreated out-patients, visiting a hypertension policlinic, in Uppsala, Sweden. Three hundred men and 170 women with a mean age of 57 years were investigated. Measurements were taken by: physical examination (body mass index, waist-to-hip ratio, blood pressure); intravenous glucose tolerance test (IVGTT); euglycaemic hyperinsulinaemic clamp; and blood sampling for lipoprotein lipid fractions, uric acid, and free fatty acids. The results were that pre-menopausal women showed a higher insulin-mediated glucose disposal (7.6 vs5.8 mg/kg/min; P < 0. 01), and lower fasting glucose (4.9 vs 5.2 mmol/l; P < 0.05) than men, as well as a more advantageous lipoprotein profile. However, in post menopausal women insulin sensitivity decreased and the lipoprotein profile deteriorated. Women still showed higher levels of high-density lipoprotein (HDL)-cholesterol, and men a higher waist-to-hip ratio and levels of uric acid, in both age groups. It was concluded that post-menopausal hypertensive women are relatively more insulin resistant than pre-menopausal ones in comparison with men in the same age group and with the same degree of overall obesity. Journal of Human Hypertension (2000) 14, 51-56.

Age Factors↗
PubMed2000

The impairment in endothelial function induced by non-esterified fatty acids can be reversed by insulin.

Dyslipidaemia, with elevations of circulating triacylglycerols (triglycerides) and non-esterified (free) fatty acids, and hyperinsulinaemia are often found in the same subjects, the so-called 'insulin resistance syndrome'. The present study aims to investigate how elevated levels of non-esterified fatty acids, hyperinsulinaemia and the combination of these factors affects endothelium-dependent vasodilatation (EDV). Ten volunteers were examined on two occasions. Intralipid (plus heparin) or saline (0.9% NaCl) was infused for 4 h. During the final 2 h, euglycaemic hyperinsulinaemia (80+/-4 m-units/l) was imposed. EDV and endothelium-independent vasodilatation were evaluated in the forearm by local intra-arterial infusion of methacholine or sodium nitroprusside at baseline and after 2 and 4 h. Forearm blood flow was measured by venous occlusion plethysmography. Lipid oxidation was determined by measuring plasma malondialdehyde levels. Infusion of Intralipid plus heparin increased the concentration of non-esterified fatty acids to 2.6+/-1.2 mmol/l and decreased EDV from 27.6+/-8.7 to 21.0+/-5.7 ml x min(-1) x 100 ml(-1) tissue (P < 0.01). This effect was completely reversed by hyperinsulinaemia (P < 0.01). Hyperinsulinaemia alone increased EDV (to 30.4+/-9.5 ml x min(-1) x 100 ml(-1) tissue; P < 0.01), while endothelium-independent vasodilatation was unaltered by the interventions. Infusion of Intralipid plus heparin increased malondialdehyde levels from 0.67+/-0.22 to 1.2+/-0.37 micromol/l (P < 0.001), while hyperinsulinaemiadid not change the malondialdehyde level. In conclusion, an acute increase in serum levels of non-esterified fatty acids increased lipid oxidation and decreased EDV. The effect on EDV of non-esterified fatty acids could be reversed by hyperinsulinaemia.

Adult↗
PubMed2000

Oral dehydroepiandrosterone (DHEA) replacement therapy in women with Addison's disease.

OBJECTIVE: Patients with primary adrenocortical failure (Addison's disease) have abnormally low levels of DHEA and androgens relative to age. To define a suitable dose, the effect of oral dehydroepiandrosterone (DHEA) replacement therapy in women with Addison's disease (n = 9) was evaluated. DESIGN AND MEASUREMENTS: DHEA was administered as a daily oral dose of either 50 mg (n = 5) or 200 mg (n = 4). Blood sampling and measurements of insulin sensitivity (as measured with euglycemic insulin clamp technique) and body composition (as measured by dual energy X-ray absorptiometry) were performed before and during DHEA treatment and at a 3-month follow up. RESULTS: DHEA and DHEA(S) levels were restored to normal in those patients receiving 50 mg whereas DHEA(S) level was slightly above the normal reference value in those receiving 200 mg. Circulating levels of androgens (androstenedione, testosterone and testosterone/SHBG ratio) were normalized in all patients. A slight rise in IGF-1 levels was seen in both groups as was a decrease in the levels of low and high density lipoproteins. No effect on blood glucose levels or insulin sensitivity was seen and no change of body composition was observed. No serious side-effects were seen, but some of the patients experienced increased apocrine sweat secretion (n = 7), itchy scalp (n = 2) and acne (n = 7), all of which were reversed when DHEA was discontinued. CONCLUSION: A daily replacement dose of 50 mg of DHEA results in near physiological levels of DHEA, DHEA(S) androstenedione and testosterone in women with Addison's disease, without severe side-effects.

Addison Disease↗
PubMed2000

Direct medical costs for patients with type 2 diabetes in Sweden.

OBJECTIVES: To estimate the total direct medical costs to society for patients with type 2 diabetes in Sweden and to investigate how different factors, for example diabetic late complications, affect costs. DESIGN: Cross-sectional data regarding health care utilization, clinical characteristics and quality of life, were collected at a single time-point. Data on resource use cover the 6-month period prior to this time point. SETTING: Patient recruitment and data collection were performed in nine primary care centres in three main regions in Sweden. SUBJECTS: Only patients with an age at diabetes diagnosis >/= 30 years (type 2 diabetes) were included (n = 777). RESULTS: The total annual direct medical costs for the Swedish diabetes type 2 population were estimated at about 7 billion SEK (Swedish Kronor) in 1998 prices, which is about 6% of the total health care expenditures and more than four times higher than the former Swedish estimate obtained when using diabetes as main diagnosis for calculating costs. The annual per patient cost was about 25 000 SEK. The largest share of this cost was hospital inpatient care. Costs increased with diabetes duration and were higher for patients treated with insulin compared to those treated with oral hypoglycaemic drugs or with life style modification only. Patients with both macro- and microvascular complications had more than three times higher costs compared with patients without such complications. CONCLUSIONS: Type 2 diabetes is a serious and expensive disease and the key to reducing costs seems to be intensive management and control in order to prevent and delay the associated late complications.

Adult↗
PubMed2000

Prediction models for insulin resistance in the polycystic ovary syndrome.

Women with the polycystic ovary syndrome (PCOS) have a high prevalence of insulin resistance, with consequent increased risk of metabolic diseases later in life. An early metabolic screening would therefore be of clinical relevance. By using stepwise regression analysis on several variables obtained in 72 women with PCOS, we constructed simple and reliable mathematical models predicting insulin sensitivity, as measured by the euglycaemic hyperinsulinaemic clamp. The normal ranges of insulin sensitivity were calculated from 81 non-hirsute, normally menstruating women with normal ovaries, and similar body mass index (BMI) and age as the women with PCOS. Measured variables included BMI, waist and hip circumferences, truncal-abdominal skin folds, circulating concentrations of gonadotrophins, androgens, sex hormone-binding globulin (SHBG), triglycerides, total cholesterol and cholesterol subfractions, fasting insulin, C-peptide and free fatty acids. The three best prediction models included waist circumference, together with insulin (model I: R(2) = 0.77), serum triglycerides (model II: R(2) = 0.65), and the subscapularis skin fold (model III: R(2) = 0. 64). Using reference limits for insulin sensitivity obtained in the 81 normal pre-menopausal women, the models identify insulin resistant women with PCOS. These simple and inexpensive models are potentially useful in clinical practice as an early screening in women with PCOS.

Adolescent↗
PubMed2000

Beta-cell activity and destruction in type 1 diabetes.

Type 1 diabetes is the result of a chronic inflammatory process that causes elimination of insulin-producing beta-cells, resulting in insulin deficiency and hyperglycemia. The destruction is thought to be mediated by an autoimmune process involving cytotoxic T cells recognizing beta-cell autoantigens in the context of MHC class I-peptide complexes. Autoantibodies against insulin, glutamic acid decarboxylase (GAD) and and ICA 512 protein tyrosine phosphatase are frequently found. At the clinical onset of diabetes, some beta-cells remain and after initiation of insulin treatment, most patients enter a period of remission, a phenomenon that may reflect diminished autoimmune activity in the islets. There is evidence to suggest that a further loss of beta-cells can be curtailed, and that patients, who maintain endogenous insulin production, have better glycemic control and less risk of complications. This is the basis for our current research. We are characterizing the remission phenomenon in epidemiological studies in order to identify determinants of beta-cell survival. In randomized, prospective multicenter trials, we are evaluating the benefit of beta-cell secretory rest for rescue of insulin production in patients at onset of clinical disease. In experimental studies, we are investigating expression and regulation of the key molecules of an autoimmune process in the islets. Further, selective beta-cell damage is induced in rat islets and measures to enhance beta-cell resistance and repair are being examined. We have recently identified a remarkable, beta-cell protective effect of K(ATP)-channel opening.

Animals↗
PubMed2000

The increase in sympathetic nerve activity after glucose ingestion is reduced in type I diabetes.

Food intake is followed by an increase in baroreflex-governed sympathetic outflow to muscle vessels. It is established that insulin contributes to this stimulation; however, the increase occurs (to a lesser degree) even in the absence of enhanced insulin secretion. To further elucidate the role of insulin, muscle nerve sympathetic activity was recorded by microneurography, and the increase after an oral 100-g glucose load in eight C-peptide-negative patients with type I diabetes without any signs of neuropathy was compared with that in 16 healthy control subjects. The level of sympathetic activity at rest was similar in the two groups (type I diabetes patients, 19.5+/-2.4 bursts/min; controls, 20.4+/-4.8 bursts/min; means+/-S.D.). Following glucose intake there was a significant increase in activity in both groups, with maximum values at 30 min of 24.3+/-3.7 bursts/min for type I diabetes patients and 34.4+/-9.1 bursts/min for controls. The summarized response (during 90 min) of the diabetic patients was less than half that of the control subjects (P=0.0003). It is concluded that the response of muscle nerve sympathetic activity to glucose ingestion is reduced to about half of its normal strength in the absence of insulin, and that there is no difference in sympathetic outflow at rest between healthy subjects and diabetic patients without polyneuropathy.

Adult↗
PubMed1999

[Health economics analysis of diabetes is necessary. It facilitates decision-making and international comparison].

Cost-of-illness studies have shown diabetes to be associated with substantial direct and indirect costs, accounting for 5-6 percent of total health care expenditure. In a Swedish study, where total costs were divided into costs due to management of diabetes and costs due to complications, the total annual cost to the community was estimated to be SEK 5.7 billion in 1994, costs due to complications being the major item, accounting for over 75 per cent of the total. There have been few other Swedish studies of costs for diabetes or diabetes-related complications. The most widely studied category of complications is diabetes-related foot ulcers, with an estimated annual cost of SEK 1-2 billion. However, earlier studies were marred by shortcomings: costs estimated for the main diagnosis only, without breakdown into categories or distinction between type 1 and type 2 diabetes, sources of data other than official data-bases ignored, etc. Diabetes care in Sweden is of high quality, and substantial clinical, epidemiological and health economics research has been carried out. It is important that Sweden contributes to international research on health economics aspects of diabetes.

Controlled Clinical Trials as Topic↗
PubMed1999

Health-related quality of life in insulin-treated diabetic patients in the Sudan.

To determine health-related quality of life (HRQL) in people with insulin-treated diabetes mellitus in Sudan, a total of 89 patients aged 25-55 years and with > or = 5 years diabetes duration was studied. HRQL was measured with a 68-item questionnaire from the Medical Outcomes Study. Late diabetic complications were assessed, and haemoglobin A1c (HbA1c) was measured to assess the metabolic control. Of the patients (m = 36; f = 53), only 13.5%, had good metabolic control ((HbA1c) < 7.5%). These patients rated their HRQL as worse than patients with poor metabolic control ((HbA1c) > 10%). However, the latter were significantly younger, had shorter diabetes duration, and were free from late complications. Overall, 49.4% of the patients had one or more of the late diabetic complications. These patients rated their HRQL significantly lower when compared with patients without complications. Older age and the presence of late diabetic complications were the most important predictors for HRQL. It is concluded that self-rated HRQL in this group of patients is generally low. Improving diabetes knowledge and the metabolic control since early in the course of the disease, will not only retard the development of late complications, but will certainly improve the HRQL of these patients.

Adult↗
PubMed1999

Plasma endothelin-1 and total insulin exposure in diabetes mellitus.

Insulin stimulates endothelin-1 (ET-1) expression in a dose-response relationship, and ET-1 effects on vascular wall structure are similar to the long-term complications of diabetes. We therefore determined whether the plasma ET-1 concentration in patients with diabetes is associated with their total insulin exposure to see if plasma ET-1 might be a link between insulin exposure and long-term complications of diabetes. We studied 69 patients with Type I and 40 patients with Type II diabetes mellitus in equally tight glycaemic control for 2 years in a cross-sectional design. We measured basal and glucagon-stimulated plasma C-peptide, abdominal sagittal diameter, skinfold thickness, glomerular filtration rate, albumin excretion rate and standard clinical characteristics. Mean HbA1c was 6.4% in Type I and 6.3% in Type II diabetes. Patients with an albumin excretion rate >300 microg/min were excluded. Adjusted mean plasma ET-1 was 4.11 (S.E.M. 0.39) pg/ml in 21 normal subjects, 3.47 (0.19) pg/ml in Type I diabetes and 4.84 (0.26) pg/ml in Type II diabetes (P=0.0001). In all patients with measurable plasma C-peptide, plasma ET-1 was associated with basal plasma C-peptide (r=0.5018, P<0.0001), with stimulated plasma C-peptide (r=0.5379, P<0.0001), and with total daily insulin dose (r=0.2219, P=0.00851). Abdominal obesity, metabolic abnormalities, blood pressure and glomerular filtration rate were not associated with plasma ET-1, when corrected for C-peptide and daily insulin dose. Our study shows that the plasma concentration of ET-1 is closely associated with insulin secretion and insulin dose in patients with diabetes. Plasma ET-1 is higher in Type II diabetes than in Type I diabetes. Increased insulin exposure in patients with diabetes may have long-term effects on vascular wall structure through its stimulation of ET-1 expression.

Adult↗