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Patients with cystic fibrosis (CF) are underweight and growth retarded. This study tested the link between serum insulin‐like growth factor‐I (IGF‐I) and insulin‐like growth factor‐binding protein‐3 (IGFBP‐3) levels and body height,... more
Patients with cystic fibrosis (CF) are underweight and growth retarded. This study tested the link between serum insulin‐like growth factor‐I (IGF‐I) and insulin‐like growth factor‐binding protein‐3 (IGFBP‐3) levels and body height, nutritional status, pulmonary function tests and activity of inflammation in 92 subjects with CF (age 2.1–18.8 y). It also analysed the effect of short‐term antibiotic treatment and hyperalimentation on IGF‐I and IGFBP‐3 levels in 33 subjects (age 3.6–33.7 y) on 41 occasions. Both IGF‐I (‐1.19 ±0.17 SD) and IGFBP‐3 levels (‐0.66 ±0.12 SD; both p 0.0001 vs 0) were decreased in cross‐sectional measurements. Their standardized values were inversely proportional to age (IGF‐I: r= ‐0.23, p= 0.03; IGFBP‐3: r= ‐0.29, p= 0.005) and positively correlated with SDS of height (IGF‐I: r= 0.40, p 0.0001; IGFBP‐3: r= 0.36, p= 0.0005) and of mid‐arm circumference (IGF‐I: r= 0.39, p= 0.0001; IGFBP‐3: r= 0.38, p= 0.0002), and with pulmonary function tests. After a short‐term course of intensive antibiotic therapy and hyperalimentation, IGF‐I normalized (from ‐0.66 ± 0.20 to 0.00 ± 0.25 SD; pľ 0 0001) and IGFBP‐3 increased (from ‐0.78 ± 0.15 to ‐0.53 ± 0.16 SD; p= 0.002). IGFBP‐3 correlated inversely with erythrocyte sedimentation rate (r= ‐0.40, p= 0.01).
Research Interests: Endocrinology, Cystic Fibrosis, Adolescent, Medicine, Growth, and 15 moreHumans, Child, Internal Medicine, Insulin, Female, Male, Underweight, Longitudinal Studies, Adult, Combination drug therapy, Body Height, Growth Factor, Cross Sectional Studies, Insulin Like Growth Factor, and Paediatrics and reproductive medicine
Research Interests: Prosthesis, Medicine, Humans, Female, Pubmed, and 4 moreAged, Middle Aged, prosthesis Design, and Reoperation
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Research Interests: Endocrinology, Type 2 Diabetes, Medicine, Humans, Internal Medicine, and 13 moreMetformin, Insulin, Diabetes mellitus, Follow-up studies, Body Mass Index, Middle Aged, Oral Hypoglycemic Agents, Type 2 Diabetes Mellitus, Growth Factor, Weight Gain, Insulin Like Growth Factor, The American, and Medical and Health Sciences
ABSTRACT Meeting Abstract: 600
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Hyperhidrosis affects 2.8% of the population and has severe negative influence on life quality. The disease is represented in many specialties but can unfortunately be incorrectly treated or not treated at all. Primary hyperhidrosis is... more
Hyperhidrosis affects 2.8% of the population and has severe negative influence on life quality. The disease is represented in many specialties but can unfortunately be incorrectly treated or not treated at all. Primary hyperhidrosis is the most common form. Secondary hyperhidrosis is most often excluded by a few anamnestic data. Botulinum toxin and anticholinergics are adequate treatment options when aluminium chloride is insufficient. This article describes the disease from the physician's as well as the patient's perspective. Furthermore, examination procedures and treatment procedures are presented.
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Robinson, I.C.A.F. and Clark, R.G. (National Institute for Medical Research, Mill Hill, London, UK). Growth promoting activity of IGF-I in the rat. Acta Paediatr Scand [Suppl] 347: 93, 1988. According to the original somatomedin... more
Robinson, I.C.A.F. and Clark, R.G. (National Institute for Medical Research, Mill Hill, London, UK). Growth promoting activity of IGF-I in the rat. Acta Paediatr Scand [Suppl] 347: 93, 1988. According to the original somatomedin hypothesis, GH promotes growth by generating ‘somatomedins’ or insulin-like growth factors (IGFs) in the liver. The advent of large amounts of IGF-I produced by recombinant DNA technology has now allowed testing of this hypothesis, by comparing the growth promoting activity of IGF-I and GH in three animal models of growth deficiency. When injected or infused subcutaneously, or infused intravenously, IGF-I is a weak growth promoter in the hypophysectomized rat compared with GH, even when infused in combination with small amounts of GH. Growth arrest in the diabetic rat was corrected by insulin infusion which also restored GH secretion. lnsulin or IGF-I caused a large initial weight gain in diabetic rats, accompanied by a partial correction of food and water balance, even in the presence of persistent hyperglycaemia. A new mutant GH deficient dwarf rat grows in response to both GH and IGF-I infusions, but these agents elicit different patterns of organ growth. For the same overall body growth, GH was more effective in stimulating bone growth, whereas IGF-I stimulated renal and splenic growth. This new dwarf rat may prove useful for the study of the relative growth promoting effects of IGF-I and GH in more detail in future.
Research Interests: Adolescent, Medicine, Humans, Child, Circadian Rhythm, and 3 morePubmed, Age Factors, and Somatomedin
Evidence has recently indicated that the MRAS and HNF1A genetic polymorphisms are associated with coronary artery disease. The MRAS and HNF1A genes are located on chromosomes 3q and 12q within the regions where associations with diabetes... more
Evidence has recently indicated that the MRAS and HNF1A genetic polymorphisms are associated with coronary artery disease. The MRAS and HNF1A genes are located on chromosomes 3q and 12q within the regions where associations with diabetes and diabetic nephropathy occur. We thus performed genetic and functional analyses of these two genes to evaluate their impacts on diabetes and diabetic nephropathy. MRAS and HNF1A genetic polymorphisms were genotyped in 1399 Czech subjects including non-diabetic controls (339), type 1 (243) and type 2 (817) diabetic patients with and without diabetic nephropathy using TaqMan allelic discrimination. Gene expression levels in the kidneys of diabetic Goto-Kakizaki and Wistar rats were detected with real-time RT-PCR. Despite no significance in genetic analysis of diabetic subjects, SNP rs2259816 in the HNF1A gene tended to associate with diabetic nephropathy in type 1 diabetic patients. The hnf1a gene expression was significantly decreased in kidney tissues of Goto-Kakizaki rats compared to Wistar and insulin-treated Goto-Kakizaki rats. There was neither significant association in the MRAS genetic polymorphism with diabetic nephropathy nor variation of mras gene expression in the kidneys of Goto-Kakizaki and Wistar rats. Data from the present study have not proved any significant association of the MRAS and HNF1A genetic polymorphisms with diabetes and diabetic nephropathy in a cohort of Czech population. However, the functional analysis and the trend in genetic analysis suggest that the HNF1A gene may have primary genetic impact on the development of diabetic nephropathy.
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Research Interests: Diabetes, Biology, Medicine, Genotype, Snp, and 3 moreSingle Nucleotide Polymorphism, Albuminuria, and Icam-1
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INTRODUCTION Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 (IGFBP-1) play an important role in vascular health. Many patients with type 1 diabetes are medicated with HMG-CoA reductase inhibitors,... more
INTRODUCTION Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 (IGFBP-1) play an important role in vascular health. Many patients with type 1 diabetes are medicated with HMG-CoA reductase inhibitors, statins, in order to prevent vascular complications. Yet little is known about the effect of statins on the IGF-1/IGFBP-1 axis in these patients. OBJECTIVES The aim of this study was to evaluate the effect of atorvastatin treatment on IGF-1 and IGFBP-1 with regards to microvascular function. DESIGN Twenty patients with type 1 diabetes received either placebo or 80mg atorvastatin for two months in a double-blinded cross-over study. IGF-1 and IGFBP-1 levels were assessed before and after each treatment period. Skin microcirculation was studied using Doppler perfusion imaging during iontophoresis of acetylcholine and sodium nitroprusside to assess endothelium-dependent and endothelium-independent microvascular reactivity, respectively. RESULTS Treatment with high-dose atorvastatin was associated with a significant decrease in IGF-1 levels compared to placebo (p<0.05, ANOVA repeated measures), whereas no effect was seen on IGFBP-1 or the IGF-1/IGFBP-1 ratio. These variables did not correlate with measurements of skin microvascular reactivity. CONCLUSIONS The study found that treatment with high-dose atorvastatin was associated with reduced IGF-1 levels, which may indicate a potential negative effect on microvascular function and long-term risk of microangiopathy development.
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Research Interests: Nursing, Biomarkers, Medicine, Anorexia Nervosa, Bulimia Nervosa, and 15 moreNeurocognitive, Cephalometry, Humans, Female, Nutritional Status, Neurocognitive development, Ferritin, Longitudinal Studies, Adult, Offspring, Feeding and Eating Disorders, hydrocortisone, Paediatrics and reproductive medicine, Neurocognitive disorders, and Head Circumference
Research Interests: Chemistry, Diabetes, Asthma, Clinical Biochemistry, Carotenoids, and 15 moreAntioxidants, Female, Gene, Cervical Cancer, Diabetic Nephropathy, Clinical Sciences, Antioxidant enzyme, Adult, Enzyme activity, Case Control Study, Allele, Cervical Intraepithelial Neoplasia, Case Control Studies, alleles, and Gene frequency
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SNAP-25 is a protein involved in regulated membrane fusion and part of the SNARE complex. It exists as two splicing variants, SNAP-25a and SNAP-25b, which differ in 9 out of 206 amino acids. SNAP-25 together with Syntaxin 1 and VAMP-2... more
SNAP-25 is a protein involved in regulated membrane fusion and part of the SNARE complex. It exists as two splicing variants, SNAP-25a and SNAP-25b, which differ in 9 out of 206 amino acids. SNAP-25 together with Syntaxin 1 and VAMP-2 forms the ternary SNARE complex essential for mediating activity-dependent release of hormones and neurotransmitters. The functional difference between SNAP-25a and SNAP-25b is poorly understood as both can participate in SNARE complexes and mediate membrane fusion. However, we recently demonstrated that SNAP-25b-deficiency results in metabolic disease and increased insulin secretion. Here we investigated if SNAP-25a and SNAP-25b differently affect interactions with other SNAREs and SNARE-interacting proteins in mouse hippocampus. Adult mice almost exclusively express the SNAP-25b protein in hippocampus whereas SNAP-25b-deficient mice only express SNAP-25a. Immunoprecipitation studies showed no significant differences in amount of Syntaxin 1 and VAMP-2 co-precipitated with the different SNAP-25 isoforms. In contrast, Munc18-1, that preferentially interacts with SNAP-25 via Syntaxin 1 and/or the trimeric SNARE complex, demonstrated an increased ability to bind protein-complexes containing SNAP-25b. Moreover, we found that both SNAP-25 isoforms co-precipitated the Gβγ subunits of the heterotrimeric G proteins, an interaction known to play a role in presynaptic inhibition. We have identified Gβ1 and Gβ2 as the interacting partners of both SNAP-25 isoforms in mouse hippocampus, but Gβ2 was less efficiently captured by SNAP-25a. These results implicate that the two SNAP-25 isoforms could differently mediate protein interactions outside the ternary SNARE core complex and thereby contribute to modulate neurotransmission.
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Recent genome-wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity-related traits. Outside Western populations the associations between these variants have not always been consistent and... more
Recent genome-wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity-related traits. Outside Western populations the associations between these variants have not always been consistent and in Indians it has been suggested that FTO relates to diabetes without an obvious intermediary obesity phenotype. We investigated the association between genetic variants in FTO (rs9939609) and near MC4R (rs17782313) with obesity- and type 2 diabetes (T2DM)-related traits in a longitudinal birth cohort of 2,151 healthy individuals from the Vellore birth cohort in South India. The FTO locus displayed significant associations with several conventional obesity-related anthropometric traits. The per allele increase is about 1% for BMI, waist circumference (WC), hip circumference (HC), and waist-hip ratio. Consistent associations were observed for adipose tissue-specific measurements such as skinfold thickness reinforcing the association with obesity-related traits. Obesity associations for the MC4R locus were weak or nonsignificant but a signal for height (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) was observed. The effect on obesity-related traits for FTO was seen in adulthood, but not at younger ages. The loci also showed nominal associations with increased blood glucose but these associations were lost on BMI adjustment. The effect of FTO on obesity-related traits was driven by an urban environmental influence. We conclude that rs9939609 variant in the FTO locus is associated with measures of adiposity and metabolic consequences in South Indians with an enhanced effect associated with urban living. The detection of these associations in Indians is challenging because conventional anthropometric obesity measures work poorly in the Indian &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;thin-fat&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; phenotype.
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Research Interests: Endocrinology, Aging, Endometrial Cancer, Bicycling, Blood Glucose, and 15 moreClinical, Body Composition, Body Mass Index, Athletes, Clinical Sciences, Adult, Cognitive Function, Body Fat, Free Fatty Acid, Endurance Training, Case Control Study, Age Groups, Confidence Interval, Endocrine System, and dehydroepiandrosterone sulfate
P03-16 Correlations of adiponectin with IGFBP-1 in Swedish men with and without type 2 diabetes H.F. Gu, T. Gu, A. Hilding, L. Karvestedt, A. Flyvbjerg, J. Frystyk, C.-G. Ostenson, K. Brismar. Karolinska Institutet, Molecular Medicine and... more
P03-16 Correlations of adiponectin with IGFBP-1 in Swedish men with and without type 2 diabetes H.F. Gu, T. Gu, A. Hilding, L. Karvestedt, A. Flyvbjerg, J. Frystyk, C.-G. Ostenson, K. Brismar. Karolinska Institutet, Molecular Medicine and Surgery, Stockholm, Sweden; Stockholm Sjukhem, Stockholm, Sweden; Aarhus University Hospital, Medical Research Laboratories, Institute of Clinical Medicine & Department of Endocrinology and Internal Medicine, Aarhus, Denmark
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Research Interests: Endocrinology, Immunohistochemistry, Medicine, Cell line, Humans, and 14 moreInternal Medicine, Diabetes mellitus, Female, Male, Diabetic Nephropathy, Middle Aged, Genotype, Adult, Single Nucleotide Polymorphism, Allele, Diabetes Care, Hypoxia inducible factor, Medical and Health Sciences, and Diabetic nephropathies
OBJECTIVE To study the influence of type 2 diabetes on the insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) serum levels in an area-based population of type 2 patients previously described.... more
OBJECTIVE To study the influence of type 2 diabetes on the insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) serum levels in an area-based population of type 2 patients previously described. RESULTS The patients (n = 151) were elderly (70.6 +/- 0.7 years of age) and moderately overweight (BMI 27.0 +/- 0.4 kg/m2). Most patients (83%) were treated with either diet alone or diet in combination with sulphonylurea. Metabolic control measured as HbAlc deteriorated with duration (p < 0.001) and between groups treated with diet (HbA1c 5.8 +/- 0.6), sulphonylurea (7.5 +/- 0.2) and insulin (7.7 +/- 0.4). Mean levels of IGF-I were within reported normal range, but were lower in the insulin-treated as compared to the non-insulin-treated patients. Levels of IGF-I decreased with diabetes duration and with increased blood glucose. There was a positive correlation between IGF-I and insulin levels and also an inverse correlation between IGF-I and IGFBP-1 levels. The IGFBP-1 levels were twofold higher than reported in non-diabetic individuals. In multiple stepwise correlation analysis, 37% of the variability in IGFBP-1 could be explained by BMI, IGF-I SD score, age, IGF-I, and fasting blood glucose. CONCLUSION Our study indicates that influence of type 2 diabetes on IGF-I bioavailability in individual patients is modulated by insulin, body weight (presumably reflecting insulin sensitivity) and metabolic control. Furthermore, increased levels of IGFBP-1 are strongly associated with decreased b-cell function in type 2 diabetes mellitus.
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AIMS Compare quantitative ultrasound (QUS) of calcaneus and dual energy X-ray absorptiometry (DXA) as measurements of bone density, calculate 20-year fracture incidence in patients with T1DM and T2DM and multiple complications, and... more
AIMS Compare quantitative ultrasound (QUS) of calcaneus and dual energy X-ray absorptiometry (DXA) as measurements of bone density, calculate 20-year fracture incidence in patients with T1DM and T2DM and multiple complications, and compare the methods' predictive ability. METHODS Sixty-two hospital foot clinic patients with T1DM or T2DM and complications were followed (1995-2015; 610 person-years). Clinical assessments and QUS of calcaneus were performed on all at inclusion and DXA of the spine and femoral neck on a subgroup (n=34). Fracture incidence was assessed at follow-up and compared to incidence in the general population. We evaluated the correlation between QUS of calcaneus and DXA (Pearson's correlation test) and the association between bone density and fracture incidence at follow-up (logistic regression). RESULTS Bone density (QUS of calcaneus) correlated with hip bone density (DXA). Incidence of all fractures (30/62 patients; 48%) and hip fractures (6/62 patients; 10%) was higher in patients than the general population. Twelve (19%) experienced foot fracture. QUS of calcaneus predicted hip, lower leg, and foot fractures; DXA did not. CONCLUSIONS Because QUS of calcaneus predicted fractures in patients with diabetes and multiple complications, it seems appropriate to test QUS of calcaneus as a fracture risk predictor in primary care.
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Research Interests: Diabetes, Wound Healing, Vibration, Type 2 Diabetes, Medicine, and 13 moreBiopsy, Humans, Diabetes mellitus, Skin, Body Mass Index, Diabetic Foot, Middle Aged, Type 2 Diabetes Mellitus, Reference Values, Diabetes Care, Age of Onset, Vascular Endothelial Growth Factor, and Medical and Health Sciences
The aim of the present study was to investigate whether the diurnal variability of B-Glucose is dependent on GH, IGF-I and IGFBP-1 levels, apart from insulin, and if there is any difference between Tanner stages 3 and 5. Five boys in... more
The aim of the present study was to investigate whether the diurnal variability of B-Glucose is dependent on GH, IGF-I and IGFBP-1 levels, apart from insulin, and if there is any difference between Tanner stages 3 and 5. Five boys in Tanner stage 3 and 6 boys in stage 5 with type 1 diabetes were included. Blood was continuously collected from a cubital vein for 24 h. S-Insulin, S-GH, S-IGF-I and S-IGFBP-1 were analysed. B-Glucose was analysed hourly at bedside. One week before and 1 wk after the 24-h study period the participants performed self-monitoring of blood glucose (SMBG) during normal physiologic conditions. In the 24-h profile of B-Glucose, insulin, IGFBP-1 and GH, we found a significant positive correlation between B-Glucose and log IGFBP-1 (r = 0.5, p = 0.005) and an inverse correlation to insulin (r = -0.5, p = 0.004) but no correlation to logGH (r = -0.04, p = 0.831). In multiple regression analysis, B-Glucose was still significantly correlated to log IGFBP-1, when adjusting for insulin and GH, in Tanner stage 5. We found a difference between Tanner stages 3 and 5 in the variability of B-Glucose over a longer period during normal daily activity (p = 0.02), but not over the 24-h study period. We have demonstrated in type 1 diabetes adolescent boys a relationship between simultaneously measured blood-glucose and IGFBP-1 levels independent of the insulin and GH levels, suggesting that the free fraction of IGF-I influences the glucose metabolism.
Research Interests: Endocrinology, Adolescent, Type 2 Diabetes, Medicine, Humans, and 13 moreChild, Internal Medicine, Glucose, Insulin, Diabetes mellitus, Blood Pressure, Circadian Rhythm, Male, Clinical Sciences, Regulator, Type 2 Diabetes Mellitus, Insulin Like Growth Factor, and Paediatrics and reproductive medicine
The organ content of the mevalonate pathway lipids was investigated in liver-X-receptor (LXR) α, β and double knock-out mice. An extensive or moderate increase of total cholesterol in the double KO mice was found in all organs elicited by... more
The organ content of the mevalonate pathway lipids was investigated in liver-X-receptor (LXR) α, β and double knock-out mice. An extensive or moderate increase of total cholesterol in the double KO mice was found in all organs elicited by the increase of the esterified form. In LXRα and double KO mice, coenzyme Q (CoQ) was decreased in liver and increased in spleen, thymus and lung, while dolichol was increased in all organs investigated. This effect was confirmed using LXR- agonist GW 3965. Analysis of CoQ distribution in organelles showed that the modifications are present in all cellular compartments and that the increase of the lipid in mitochondria was the result of a net increase of CoQ without changing the number of mitochondria. It appears that LXR influences not only cellular cholesterol homeostasis but also the metabolism of CoQ and dolichol, in an indirect manner.