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H Beck-Nielsen

Publications and source records attributed to H Beck-Nielsen.

At least 55 records · Page 3Linked to original sources
PubMed2001

Clinical impact of mild carbohydrate intolerance in pregnancy: a study of 2904 nondiabetic Danish women with risk factors for gestational diabetes mellitus.

OBJECTIVE: The objective was to study the clinical impact of mild carbohydrate intolerance in pregnant women with risk factors for gestational diabetes mellitus. STUDY DESIGN: This was a historical cohort study of 2904 pregnant women examined for gestational diabetes on the basis of risk factors. Information on oral glucose tolerance test results and clinical outcomes was collected from laboratory charts and medical records. RESULTS: The following outcomes increased significantly with increasing glucose values during the oral glucose tolerance test: shoulder dystocia, macrosomia, emergency cesarean section, assisted delivery, hypertension, and induction of labor. However, when corrections were made for other risk factors, hypertension and induction of labor were only marginally associated with glucose levels. CONCLUSION: In a group of nondiabetic pregnant women with risk factors for gestational diabetes, there was a graded increase in the frequency of shoulder dystocia and other maternal-fetal complications with increasing glucose levels during an oral glucose tolerance test.

Adult↗
PubMed2001

Reference intervals for glucose, beta-cell polypeptides, and counterregulatory factors during prolonged fasting.

To establish reference intervals for the pancreatic beta-cell response and the counterregulatory hormone response to prolonged fasting, we studied 33 healthy subjects (16 males, 17 females) during a 72-h fast. Glucose, insulin, C-peptide, and proinsulin levels decreased (P < 0.001), and the levels of counterregulatory factors increased during the fast [P < 0.05; glucagon and free fatty acids (FFA) with a linear increase and epinephrine, norepinephrine, and cortisol with a clear underlying circadian rhythm]. Growth hormone secretion increased from the first to third day of fasting (P < 0.05) but actually decreased from the second to third day of fasting (P = 0.03). Males had higher glucose and glucagon levels and lower FFA levels during the fast (P < 0.05), whereas no effect of gender on beta-cell polypeptides was observed. A high body mass index resulted in higher insulin and C-peptide levels during the fast (P < 0.05). In conclusion, we have provided reference intervals for glucoregulatory factors during a 72-h fast. We observed a diminished beta-cell response concomitant with an increased secretion of counterregulatory hormones. These results should be of clinical and scientific value in the investigation of hypoglycemic disorders.

Adult↗
PubMed2001

Calibration, specificity and trueness of a postheparin plasma lipoprotein lipase assay.

Measurement of lipoprotein lipase activity in postheparin plasma is generally accompanied by moderate within-run variation CV(W-R) (<10%) and higher between-run variation CV(B-R) (5-25%). A calibration system was introduced in order to improve the reproducibility of measurements and to compare lipoprotein lipase activities from different days. Every day a calibration curve for lipoprotein lipase activity was constructed. Fifteen calibration curves designed over 2 years, show linearity over the whole biological spectrum and a considerable reduction of between-run variation in lipoprotein lipase activity, from 42% to 5.3% as estimated from two control postheparin plasma samples. The lipoprotein lipase calibration system is an easy and very cheap arrangement, which makes it possible to compare lipoprotein lipase activities achieved over years. When the lipoprotein lipase control values are compared with reference lipoprotein lipase samples determined in other lipase laboratories, the calibration-control system becomes an important tool for reducing analytical bias. The article reviews the original analytical criteria of catalytic measurement of lipoprotein lipase activity and describes the implementation of the calibration-control system. We describe a model for reduction of the analytical variability in the measurement of lipoprotein lipase activity. Other standardization efforts need to be made in the future, especially to define the reference material for calibration.

Animals↗
PubMed2001

GLUT4 is reduced in slow muscle fibers of type 2 diabetic patients: is insulin resistance in type 2 diabetes a slow, type 1 fiber disease?

To gain further insight into the mechanisms underlying muscle insulin resistance, the influence of obesity and type 2 diabetes on GLUT4 immunoreactivity in slow and fast skeletal muscle fibers was studied. Through a newly developed, very sensitive method using immunohistochemistry combined with morphometry, GLUT4 density was found to be significantly higher in slow compared with fast fibers in biopsy specimens from lean and obese subjects. In contrast, in type 2 diabetic subjects, GLUT4 density was significantly lower in slow compared with fast fibers. GLUT4 density in slow fibers from diabetic patients was reduced by 9% compared with the weight-matched obese subjects and by 18% compared with the lean control group. The slow-fiber fraction was reduced to 86% in the obese subjects and to 75% in the diabetic subjects compared with the control group. Estimated GLUT4 contribution from slow fibers was reduced to 77% in the obese subjects and to 61% in type 2 diabetic patients compared with the control subjects. We propose that a reduction in the fraction of slow-twitch fibers, combined with a reduction in GLUT4 expression in slow fibers, may reduce the insulin-sensitive GLUT4 pool in type 2 diabetes and thus contribute to skeletal muscle insulin resistance.

Adult↗
PubMed2001

Assessment of hepatic insulin action in obese type 2 diabetic patients.

Defects in hepatic insulin action in type 2 diabetes and its possible underlying mechanisms were assessed in euglycemic-hyperinsulinemic clamp studies, using improved tracer methods (constant specific activity technique). Ten obese diabetic patients (age 54 years, BMI 29 +/- 0.5 kg/m(2)) and ten matched control subjects were studied at baseline (after an overnight fast) and during insulin infusions of 20- and 40-mU. m(-2). min(-1). In the diabetic patients, plasma glucose levels were normalized overnight before the studies by low-dose insulin infusion. Hepatic sinusoidal insulin levels were estimated, and plasma levels of free fatty acids (FFAs) and glucagon were determined to assess the direct and indirect effects of insulin on hepatic glucose production (HGP) in type 2 diabetes. Baseline rates of HGP (86 +/- 3 vs. 76 +/- 3 mg. m(-2). min(-1), P < 0.05) were slightly elevated in the diabetic patients compared with control subjects, despite much higher hepatic sinusoidal insulin levels (26 +/- 3 vs. 12 +/- 2 mU/l, P < 0.001). Consequently, a marked defect in the direct (hepatic) effect of insulin on HGP appeared to be present at low insulin levels. However, in response to a small increase in baseline hepatic sinusoidal insulin levels of 11 mU/l (26 +/- 3 to 37 +/- 3 mU/l, P < 0.05) in the 20-mU clamp, a marked suppression of HGP was observed in the diabetic patients (86 +/- 3 to 32 +/- 5 mg. m(-2). min(-1), P < 0.001), despite only minimal changes in FFAs (0.33 +/- 0.05 to 0.25 +/- 0.05 mmol/l, NS) and glucagon (14 +/- 1 to 11 +/- 2 pmol/l, P < 0.05) levels, suggesting that the impairment in the direct effect of insulin can be overcome by a small increase in insulin levels. Compared with control subjects, suppression of HGP in the diabetic patients was slightly impaired in the 20-mU clamp (32 +/- 5 vs. 22 +/- 4 mg. m(-2). min(-1), P < 0.05) but not in the 40-mU clamp (25 +/- 2 vs. 21 +/- 3 mg. m(-2). min(-1), NS). In the 20-mU clamp, hepatic sinusoidal insulin levels in the diabetic patients were comparable with control subjects (37 +/- 3 vs. 36 +/- 3 mU/l, NS), whereas both FFA and glucagon levels were higher (i.e., less suppressed) and correlated with the rates of HGP (R = 0.71, P < 0.02; and R = 0.69, P < 0.05, respectively). Thus, at this insulin level impaired indirect (extrahepatic) effects of insulin seemed to prevail. In conclusion, hepatic insulin resistance is present in obese type 2 diabetic patients but is of quantitative significance only at low physiological insulin levels. Defects in both the direct and the indirect effects of insulin on HGP appear to contribute to this resistance.

Blood Glucose↗
PubMed2000

Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - results of the Danish Osteoporosis Prevention Study.

OBJECTIVES: To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario. METHODS: Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45-58 years, from three to 24 months past last menstrual bleeding were recruited from a random sample of the background population. Mean age was 50. 8+/-2.8 years, and the number of person years followed was 9335.3. There were two main study arms: a randomised arm (randomised to HRT; n=502, or not; n=504) and a non-randomised arm (on HRT; n=221, or not; n=789 by own choice). First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women. RESULTS: After five years, a total of 156 fractures were sustained by 140 women. There were 51 forearm fractures in 51 women. By intention-to-treat analysis (n=2016), overall fracture risk was borderline statistically significantly reduced (RR=0.73, 95% CI: 0.50-1.05), and forearm fracture risk was significantly reduced (RR=0.45, 95% CI: 0.22-0.90) with HRT. Restricting the analysis to women who had adhered to their initial allocation of either HRT (n=395) or no HRT (n=977) showed a significant reduction in both the overall fracture risk (RR=0.61, 95% CI: 0.39-0.97) and the risk of forearm fractures (RR=0.24, 95% CI: 0.09-0.69). Compliance with HRT was 65% after five years. CONCLUSIONS: It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention.

Age Factors↗
PubMed2000

[Give them a pill?].

Explore the source record for details and available documents.

Diabetes Mellitus, Type 2↗
PubMed2000

[The clinical impact of gestational diabetes mellitus].

In Denmark, gestational diabetes mellitus (GDM) develops in about 2% of all pregnant women. The discussion of GDM is complicated by lack of consensus regarding screening methods, diagnosis and treatment. Observational studies indicate that untreated GDM is associated with an increased risk of maternal and perinatal morbidity, and that the offspring of GDM mothers tend to be at increased risk of developing diabetes and adiposity as a result of an abnormal intrauterine environment. Several follow-up studies have shown that women with previous GDM run a considerable risk of developing diabetes (especially type 2 diabetes) later in life. Intervention strategies for this high risk group are suggested.

Diabetes, Gestational↗
PubMed2000

The antiviral 2',5'-oligoadenylate synthetase is persistently activated in type 1 diabetes.

Type 1 diabetes results from autoimmune destruction of the pancreatic beta-cells. Although viruses have been implicated as etiologic factors, specific pathogenic mechanisms have not been identified. Recently, increased attention has focused on the role of the innate antiviral defense system in directing adaptive immune responses. In this context, the pathogenesis of type 1 diabetes may involve an aberrant response to endogenous or exogenous viruses or their products. The family of 2',5' oligoadenylate synthetases (2', 5' AS) are IFN-alpha-inducible, RNA-dependent effector molecules in the antiviral defense system. We show that lymphocytic 2',5' AS activity is significantly increased in type 1 diabetes, both in recent-onset and in long-standing type 1 diabetes, and in diabetic twins from monozygotic twin pairs. The activity of 2',5' AS was not elevated in patients with type 2 diabetes or multiple sclerosis thus excluding hyperglycemia or autoimmunity per se as inducing upregulation of enzyme activity. In recent-onset diabetic patients, lymphocyte levels of protein kinase p68 and MxA, two other IFN-alpha-inducible antiviral proteins, were similar to control levels. These data suggest that the increased 2',5' AS activity may reflect an aberrant response to viruses or RNA molecules originating from exogenous or endogenous sources.

2',5'-Oligoadenylate Synthetase↗
PubMed2000

Cytokine RNA levels in transiliac bone biopsies from healthy early postmenopausal women.

The cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6 induce osteoclast formation and may contribute to the development of postmenopausal osteoporosis. Cross-sectional studies have suggested that both IL-1 and IL-1ra secretion increase on estrogen withdrawal, and that postmenopausal osteoporosis is associated with an inadequate increase in monocyte IL-1ra secretion with age. We measured cytokine mRNA (IL-1beta, IL-1ra, IL-6, and TNF-alpha) directly in bone biopsies from early postmenopausal women to determine if a lower compensatory increase in IL-1ra mRNA could be demonstrated in women with rapid bone loss after the menopause. Biopsies were obtained from 23 early postmenopausal women (mean age 53.9 years) who participated in a randomized study of hormone replacement therapy (HRT) and risk factors for osteoporosis. Bone mineral density was assessed by duel energy X-ray absorptiometry at 0, 1, 2, and 5 years. Women in the control group were recruited to the biopsy study based on their observed rate of bone loss (upper or lower tertile). Consent was also obtained from 11 participants receiving HRT. Biopsies were taken at 2 years, frozen in nitrogen, and homogenized. Cytokine mRNA was measured by competitive reverse transcriptase polymerase chain reaction. The IL-1ra/IL-1beta mRNA slope for the slow-loss group was steeper (deltaF = 23.3, p < 0.01) than that observed in the fast-loss group, indicating that slower bone loss was associated with higher IL-1ra mRNA levels relative to IL-1beta. During HRT, the IL-1beta mRNA level was inversely correlated with serum estradiol (log r2 = 0.77, p < 0.01), and women with a serum estradiol below 200 pmol/L during HRT had IL-1beta, mRNA levels identical to the control group. In contrast, IL-1ra mRNA was independent of serum estradiol. Histomorphometric analysis revealed weak correlations between IL-1beta mRNA and activation frequency (r2 = 0.26, p = 0.06) and between IL-1ra and volume referent bone resorption rate (r2 = 0.19, p = 0.11). TNF-alpha was not associated with the bone loss rates or with serum estradiol, and only three samples were positive for IL-6 mRNA. The findings support the hypothesis that IL-1beta production within bone increases with declining estrogen levels, and that an increase in II-1ra protects against accelerated bone loss.

Base Sequence↗
PubMed2000

Correlations between insulin sensitivity and bone mineral density in non-diabetic men.

AIMS: To investigate relationships between bone mineral density (BMD), insulin secretion and insulin sensitivity, controlling for body composition, in view of data suggesting that hyperglycaemia [corrected] leads to decreased osteoblast proliferation and a negative calcium balance and that insulin stimulates osteoblast differentiation and collagen synthesis, with no clear evidence if this response in impaired in insulin resistance. METHODS: Femur and whole body (WB) BMD was measured in 55 male patients with ischaemic heart disease and 40 healthy men, using a Hologic QDR-2000 densitometer. Insulin sensitivity (Si) was estimated as the rate of glucose disappearance divided by the area under the insulin curve during an intravenous glucose tolerance test. RESULTS: Insulin and C-peptide levels were not correlated with BMD, but Si was a significant predictor of femur (log, r = 0.35) and WB BMD (log r = 0.29, both P<0.01), even after controlling for weight and age. Fat mass (FM) was a predictor of BMD (femur: r = 0.33 P<0.01, WB: r = 0.43 P<0.001). In the femur the association with FM disappeared when log(Si) was entered in the regression. Lean body mass (LBM) contributed significantly to BMD (r = 0.50 and r = 0.66, both P<0.001). CONCLUSIONS: These results are compatible with a direct influence of lean body mass on bone, while the impact of fat mass may consist of insulin resistance with increased insulin exposure of bone. It is hypothesized that patients with insulin resistance in the metabolic pathway do not exhibit resistance to the skeletal actions of insulin.

Blood Glucose↗
PubMed2000

No association between birth weight and Type 1 diabetes mellitus--a twin-control study.

AIMS: To investigate, by means of a twin-control study, whether there is a relationship between birth weight and Type 1 diabetes mellitus. METHODS: In the youngest part (n = 20 888 pairs) of the Danish Twin Register, 95 twin pairs (26 monozygotic and 69 dizygotic) with Type 1 diabetes were identified. Information about birth weight and birth length, prematurity, maternal age and parity was obtained from midwives' records and from the Danish Medical Birth Registry and analysed using Student's two-sided t-test, Chi-square test and logistic regression. RESULTS: Birth data were available for 83 diabetic and 51 healthy twin individuals, altogether 67 twin pairs (20 monozygotic and 47 dizygotic). Mean birth weight was 2537 g and 2565 g (NS) in monozygotic and dizygotic pairs and the corresponding length at birth 47.6 cm and 48.2 cm (NS). In pairs discordant for diabetes, the mean birth weight was 2538 g in twins with diabetes and 2549 g in twins without diabetes (NS). Logistic regression in discordant pairs showed no relationship between diabetes status and birth weight, birth length, birth order, sex or prematurity. Logistic regression in concordant vs. discordant pairs showed no effect of mean birth weight and birth length, maternal age, parity or weeks of prematurity. CONCLUSIONS: There is no association between Type 1 diabetes mellitus and birth weight in this study. Furthermore, variables related to birth weight and length cannot explain why some pairs are concordant while other remain discordant.

Birth Weight↗
PubMed2000

Maternal and perinatal outcomes in 143 Danish women with gestational diabetes mellitus and 143 controls with a similar risk profile.

AIMS: To assess maternal and fetal outcomes in pregnancies complicated by gestational diabetes mellitus (GDM) compared to non-diabetic pregnancies with an otherwise similar risk profile and to study the association between different anti-diabetic treatments and fetal outcomes. METHODS: The records of 143 consecutive GDM pregnancies and 143 non-diabetic controls matched on the basis of age, parity and pre-pregnancy body mass index (BMI) were studied. The GDM patients were treated with diet, tolbutamide and insulin. Data were collected from medical records and birth records. RESULTS: Despite treatment, the GDM group had a statistically significant higher frequency of maternal hypertension (20% vs. 11%), induction of labour (61% vs. 24%), Caesarean section (33% vs. 21%), macrosomia (14% vs. 6%), neonatal hypoglycaemia (24% vs. 0) and admission to a neonatal unit (46% vs. 12%). The risk of complications was similar in the different treatment groups. However, in the tolbutamide-treated group, one case of long-standing severe hypoglycaemia in a premature neonate occurred. CONCLUSIONS: Pregnancies complicated by GDM are associated with a higher frequency of adverse maternal and fetal outcomes. The outcomes seem to be unaffected by treatment modality. However, because of the potential risk of hypoglycaemia in some neonates, tolbutamide treatment cannot be recommended in pregnancy.

Adult↗
PubMed2000

Impact of the Xba1-polymorphism of the human muscle glycogen synthase gene on parameters of the insulin resistance syndrome in a Danish twin population.

AIMS: To establish the impact on the insulin resistance syndrome of the intron 14 Xba1-polymorphism in human muscle glycogen synthase (GYS1). METHODS: Parameters related to the insulin resistance syndrome were measured in 244 monozygotic twins and 322 dizygotic twins with or without impaired glucose tolerance. In addition a standard oral glucose tolerance test (OGTT) was performed. The twins were genotyped for Xba1-polymorphism in GYS1 intron 14. RESULTS: The allele frequency of Xba1 non-cutters (A1) was 0.95 and of cutters (A2) was 0.05. Of the 566 twins examined, 90.0% had the genotype A1A1 and the remainder had the genotype A1A2. No A2A2-genotypes were detected. In 11 genotypic discordant dizygotic twin pairs the insulin resistance was significantly increased in the twins carrying the A1A2 genotype regardless of sex (HOMA index 1.81 (A1A1) vs. 2.57 (A1A2), P < 0.05). Diastolic blood pressure was increased in female carriers of the A2-allele with impaired glucose tolerance or Type 2 diabetes mellitus (79 +/- 1 vs. 94 +/- 4 mmHg, P < 0.01). Apart from a marginal increased waist-to-hip ratio, no other elements of the insulin resistance syndrome were associated with the polymorphism. CONCLUSIONS: The Xba1-polymorphism of the human muscle glycogen synthase gene is correlated to insulin resistance and to diastolic blood pressure. The polymorphism does not involve any known transcription factor or any structural change in GYS1, and these correlations are therefore most probably caused by linkage to other functional polymorphisms in GYS1 or other gene polymorphisms on chromosome 19.

Aged↗
PubMed2000

Direct evidence of fiber type-dependent GLUT-4 expression in human skeletal muscle.

GLUT-4 expression in individual fibers of human skeletal muscles in younger and older adults was studied. Furthermore, the dependency of insulin-stimulated glucose uptake on fiber type distribution was investigated. Fiber type distribution was determined in cryosections of muscle biopsies from 8 younger (29 yr) and 8 older (64 yr) healthy subjects, and estimates of GLUT-4 expression in individual fibers were obtained by combining immunohistochemistry and stereology. GLUT-4 was more abundantly expressed in slow compared with fast muscle fibers in both younger (P < 0.007) and older (P < 0. 001) subjects. A 25% reduction of GLUT-4 density in fast fibers (P < 0.001) and an unchanged GLUT-4 density in slow fibers were demonstrated in older compared with younger subjects. Insulin-stimulated glucose uptake rates measured by hyperinsulinemic, euglycemic clamp were not correlated with the fraction of slow fibers in the young (r = -0.45, P > 0.25) or in the elderly (r = 0. 11, P > 0.75) subjects. In conclusion, in human skeletal muscle, GLUT-4 expression is fiber type dependent and decreases with age, particularly in fast muscle fibers.

Adult↗
PubMed2000

Glucose transporter expression in human skeletal muscle fibers.

The present study was initiated to investigate GLUT-1 through -5 expression in developing and mature human skeletal muscle. To bypass the problems inherent in techniques using tissue homogenates, we applied an immunocytochemical approach, employing the sensitive enhanced tyramide signal amplification (TSA) technique to detect the localization of glucose transporter expression in human skeletal muscle. We found expression of GLUT-1, GLUT-3, and GLUT-4 in developing human muscle fibers showing a distinct expression pattern. 1) GLUT-1 is expressed in human skeletal muscle cells during gestation, but its expression is markedly reduced around birth and is further reduced to undetectable levels within the first year of life; 2) GLUT-3 protein expression appears at 18 wk of gestation and disappears after birth; and 3) GLUT-4 protein is diffusely expressed in muscle cells throughout gestation, whereas after birth, the characteristic subcellular localization is as seen in adult muscle fibers. Our results show that GLUT-1, GLUT-3, and GLUT-4 seem to be of importance during muscle fiber growth and development. GLUT-5 protein was undetectable in fetal and adult skeletal muscle fibers. In adult muscle fibers, only GLUT-4 was expressed at significant levels. GLUT-1 immunoreactivity was below the detection limit in muscle fibers, indicating that this glucose transporter is of minor importance for muscle glucose supply. Thus we hypothesize that GLUT-4 also mediates basal glucose transport in muscle fibers, possibly through constant exposure to tonal contraction and basal insulin levels.

Adult↗
PubMed2000

Induction of GLUT-1 protein in adult human skeletal muscle fibers.

Prompted by our recent observations that GLUT-1 is expressed in fetal muscles, but not in adult muscle fibers, we decided to investigate whether GLUT-1 expression could be reactivated. We studied different stimuli concerning their ability to induce GLUT-1 expression in mature human skeletal muscle fibers. Metabolic stress (obesity, non-insulin-dependent diabetes mellitus), contractile activity (training), and conditions of de- and reinnervation (amyotrophic lateral sclerosis) could not induce GLUT-1 expression in human muscle fibers. However, regenerating muscle fibers in polymyositis expressed GLUT-1. In contrast to GLUT-1, GLUT-4 was expressed in all investigated muscle fibers. Although the significance of GLUT-1 in adult human muscle fibers appears limited, GLUT-1 may be of importance for the glucose supplies in immature and regenerating muscle.

Adult↗