| 1. |
- Chen, Weena J Y, et al.
(författare)
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Association of plasma osteoprotegerin and adiponectin with arterial function, cardiac function and metabolism in asymptomatic type 2 diabetic men
- 2011
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840 .- 1475-2840. ; 10, s. 67-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor superfamily, is linked to cardiovascular disease. Negative associations exist between circulating OPG and cardiac function. The adipocytokine adiponectin (ADPN) is downregulated in type 2 diabetes mellitus (T2DM) and coronary artery disease and shows an inverse correlation with insulin sensitivity and cardiovascular disease risk. We assessed the relationship of plasma OPG and ADPN and arterial function, cardiac function and myocardial glucose metabolism in T2DM.METHODS:We included 78 asymptomatic men with uncomplicated, well-controlled T2DM, without inducible ischemia, assessed by dobutamine-stress echocardiography, and 14 age-matched controls. Cardiac function was measured by magnetic resonance imaging, myocardial glucose metabolism (MMRglu) by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography. OPG and ADPN levels were measured in plasma.RESULTS:T2DM patients vs. controls showed lower aortic distensibility, left ventricular (LV) volumes, impaired LV diastolic function and MMRglu (all P < 0.05). In T2DM men vs. controls, OPG levels were higher (P = 0.02), whereas ADPN concentrations were decreased (P = 0.04). OPG correlated inversely with aortic distensibility, LV volumes and E/A ratio (diastolic function), and positively with LV mass/volume ratio (all P < 0.05). Regression analyses showed the associations with aortic distensibility and LV mass/volume ratio to be independent of age-, blood pressure- and glycated hemoglobin (HbA1c). However, the associations with LV volumes and E/A ratio were dependent of these parameters. ADPN correlated positively with MMRglu (P < 0.05), which, in multiple regression analysis, was dependent of whole-body insulin sensitivity, HbA1c and waist.CONCLUSIONS:OPG was inversely associated with aortic distensibility, LV volumes and LV diastolic function, while ADPN was positively associated with MMRglu. These findings indicate that in asymptomatic men with uncomplicated T2DM, OPG and ADPN may be markers of underlying mechanisms linking the diabetic state to cardiac abnormalities.TRIAL REGISTRATION:Current Controlled Trials ISRCTN53177482.
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| 2. |
- Bidlingmaier, Martin, et al.
(författare)
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Reference Intervals for Insulin-like Growth Factor-1 (IGF-1) From Birth to Senescence: Results From a Multicenter Study Using a New Automated Chemiluminescence IGF-1 Immunoassay Conforming to Recent International Recommendations.
- 2014
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:5
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Tidskriftsartikel (refereegranskat)abstract
- Context: Measurement of IGF-1 is a cornerstone in diagnosis and monitoring of GH-related diseases, but considerable discrepancies exist between analytical methods. A recent consensus conference defined criteria for validation of IGF-1 assays and for establishment of normative data. Objectives: Our objectives were development and validation of a novel automated IGF-1 immunoassay (iSYS; Immunodiagnostic Systems) according to international guidelines and establishment of method-specific age- and sex-adjusted reference intervals and analysis of their robustness. Setting and Participants: We conducted a multicenter study with samples from 12 cohorts from the United States, Canada, and Europe including 15ü014 subjects (6697 males and 8317 females, 0-94 years of age). Main Outcome Measures: We measured concentrations of IGF-1 as determined by the IDS iSYS IGF-1 assay. Results: A new IGF-1 assay calibrated against the recommended standard (02/254) and insensitive to the 6 high-affinity IGF binding proteins was developed and rigorously validated. Age- and sex-adjusted reference intervals derived from a uniquely large cohort reflect the age-related pattern of IGF-1 secretion: a decline immediately after birth followed by an increase until a pubertal peak (at 15 years of age). Later in life, values decrease continuously. The impact of gender is small, although across the lifespan, women have lower mean IGF-1 concentrations. Geographical region, sampling setting (community or hospital based), and rigor of exclusion criteria in our large cohort did not affect the reference intervals. Conclusions: Using large cohorts of well-characterized subjects from different centers allowed construction of robust reference ranges for a new automated IGF-1 assay. The strict adherence to recent consensus criteria for IGF-1 assays might facilitate clinical application of the results.
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| 3. |
- Ekstrom, Klas, et al.
(författare)
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Tissue IGF-I Measured by Microdialysis Reflects Body Glucose Utilization After rhIGF-I Injection in Type 1 Diabetes
- 2015
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 100:11, s. 4299-4306
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Tidskriftsartikel (refereegranskat)abstract
- Context: Type 1 diabetes is associated with portal insulin deficiency and disturbances in the GH-IGF axis including low circulating IGF-I and GH hypersecretion. Whether peripheral hyperinsulinemia and GH hypersecretion, which are relevant to the development of vascular complications, result in elevated tissue IGF-I remains unknown. Objective: The purpose of this study was to determine the relationship between whole-body glucose uptake and tissue IGF-I measured by microdialysis. Design: This was a single-blind placebo-controlled crossover study. Setting: The setting was a tertiary pediatric endocrine referral center. Participants: The participants were seven young male adults with type 1 diabetes. Intervention: After an overnight fast, a 6-h lasting euglycemic clamp was performed (constant insulin infusion at 0.5mU/kg x minute and variable glucose infusion rate [GIR]) and a subcutaneous injection of recombinant human (rh) IGF-I (120 mu g/kg) or saline was given after 2 hours. In parallel, tissue IGF-I levels were determined by microdialysis (md-IGF-I). Main Outcome Measures: md-IGF-I levels in muscle and subcutaneous fat, and GIR were determined. Results: md-IGF-I levels were detectable but unchanged after saline. After rhIGF-I, muscle and subcutaneous fat md-IGF-I increased during the second and third hour and then reached a plateau up to 10-fold higher than baseline (P less than .001). GIR was unchanged after saline, whereas it increased 2.5-fold concomitantly with the increase in md-IGF-I (P less than .0001). In contrast, serum IGF-I was increased already at 30 minutes after rhIGF-I and reached a plateau 2-fold above baseline (P less than .0001). Conclusion: We demonstrate that md-IGF-I measurements are valid and physiologically relevant by reflecting rhIGF-I-induced glucose uptake. Future studies should be conducted to elucidate the role of local tissue IGF-I in diabetic vascular complications.
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| 4. |
- Friedrich, Nele, et al.
(författare)
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Age and sex specific reference intervals across life-span for insulin-like growth factor binding protein 3 (IGFBP-3) and the IGF-I/IGFBP-3 ratio measured by new automated chemiluminescence assays.
- 2014
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:5
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Tidskriftsartikel (refereegranskat)abstract
- Context: Measurement of IGFBP-3 can aid the diagnosis of growth hormone related diseases. Furthermore, epidemiological studies suggest that IGFBP-3 and the molar IGF-I/IGFBP-3 ratio are associated with clinical endpoints like cancer or cardiovascular disease. However, their clinical use is limited by the lack of validated reference intervals. Objectives: Establishment of age- and sex-specific reference intervals for IGFBP-3 and the molar IGF-I/IGFBP-3 ratio by newly developed automated immunoassays. Setting: Multicentre study with samples from 11 cohorts from the USA, Canada and Europe Participants: 14,970 subjects healthy subjects covering all ages from birth to senescence. Main outcome measures: Concentrations of IGFBP-3 and the IGF-I/IGFBP-3 ratio as determined by the IDS iSYS IGF-I and IGFBP-3 assays. Results: Both the concentration of IGFBP-3 and the IGF-I/IGFBP-3 ratio are mainly determined by age. IGFBP-3 concentrations increase until the age of 22 years, with a plateau being visible between 15 and 25 years. Determined by the high peripubertal peak in IGF-I, the peak in the IGF-I/IGFBP-3 ratio occurs already around the age of 15, with a slightly earlier and higher peak in females. Beyond the age of 60, IGFBP-3 concentrations remain higher in females, whereas IGF-I as well as the IGF-I/IGFBP-3 ratio remain significantly higher in males. Conclusions: We present an extensive set of assay specific, age and sex-adjusted normative data for concentrations of IGFBP-3 and the molar IGF-I/IGFBP-3 ratio and demonstrate distinct sex specific differences across lifespan.
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| 5. |
- Frystyk, Jan, et al.
(författare)
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Serum adiponectin is a predictor of coronary heart disease : a population-based 10-year follow-up study in elderly men
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:2, s. 571-576
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Tidskriftsartikel (refereegranskat)abstract
- Context: Cross-sectional and nested case-control studies indicate a relationship between adiponectin, obesity, and coronary heart disease (CHD). Objective: Our objective was to investigate whether adiponectin could predict CHD in a population-based cohort of elderly men. Design and Setting: From 1991-1995 a baseline investigation was carried out in 832 healthy men aged 70 yr in the Uppsala Longitudinal Study of Adult Men (ULSAM study). They were followed up to 10.4 yr using Swedish national registry data. The baseline investigation included anthropometry, blood pressure, smoking, serum lipids, a euglycemic insulin clamp, and fasting serum adiponectin. Main Outcome Measures: Main outcome measures were defined as death or first-time hospitalization for CHD (n = 116), recorded in the Cause of Death Registry or in the Hospital-Discharge Registry of the National Board of Health and Welfare, Sweden. Associations were analyzed using Cox's proportional hazards regression, presented as hazard ratios (HR) with 95% confidence intervals (CI) for 1 SD increase in the predictor variable. Results: In a multivariable analysis including total cholesterol (HR, 1.24; CI, 1.02-1.50), high-density lipoprotein cholesterol (HR, 0.72; CI, 0.58-0.89), smoking (HR, 1.39; CI, 0.91-2.14), and systolic blood pressure (HR, 1.26; CI, 1.05-1.52), serum adiponectin was associated with lower risk for CHD (HR, 0.81; CI, 0.66-0.99). The association was independent of BMI and remained significant after adjustment for insulin sensitivity index. Conclusions: In this population-based cohort of healthy men, elevated serum levels of adiponectin were associated with a lower risk for CHD. Importantly, the association between adiponectin and CHD was independent of other well-known risk factors.
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| 6. |
- Hedman, Christina A, et al.
(författare)
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Intraperitoneal insulin delivery to patients with type 1 diabetes results in higher serum IGF-I bioactivity than continuous subcutaneous insulin infusion
- 2014
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Ingår i: Clinical Endocrinology. - : Wiley-Blackwell. - 0300-0664 .- 1365-2265. ; 81:1, s. 58-62
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveType 1 diabetes (T1D) is associated with low IGF-I and altered levels of IGF-binding proteins (IGFBPs) in plasma. This may be of importance for insulin sensitivity and the risk of developing diabetic complications. We hypothesized that IGF-I bioactivity is affected by the route of insulin administration and that continuous intraperitoneal insulin infusion (CIPII) has a more pronounced effect than continuous subcutaneous insulin infusion (CSII).Design and methodsWe compared 10 patients with T1D on CIPII with 20 age- and sex-matched patients on CSII. Blood sampling was carried out 7–9 am after an overnight fast. All patients were C-peptide negative. IGF-I bioactivity was measured in vitro using a specific IGF-I kinase receptor activation (KIRA) assay. IGF-I was also measured by immunoassay together with IGF-II, IGFBP-1 and IGFBP-2.ResultsWhen compared with subcutaneous insulin, intraperitoneal insulin resulted in (CIPII vs CSII) higher IGF-I bioactivity (1·83 ± 0·76 vs 1·16 ± 0·24 μg/l; P = 0·02), IGF-I (120 ± 35 vs 81 ± 19 μg/l; P = 0·01) and IGF-II (1050 ± 136 vs 879 ± 110 μg/l; P = 0·02). By contrast, log-transformed IGFBP-1 was reduced (P = 0·013), whereas log-transformed IGFBP-2 was not different (P = 0·12). There was a positive correlation between IGF bioactivity and IGF-I (r = 0·69; P < 0·001) and an inverse correlation between IGF-I bioactivity and log10 IGFBP-1 (r = −0·68, P < 0·001).ConclusionThe in vitro IGF-I bioactivity was higher in patients treated with CIPII compared with CSII supporting the theory that the route of insulin administration is of importance for the activity of the IGF system. Intraperitoneal insulin administration may therefore be beneficial by correcting the alterations of the IGF system in T1D.
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| 7. |
- Hedman, Christina, 1964-, et al.
(författare)
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Residual β-cell function more than glycemic control determines abnormalities of the insulin-like growth factor system in type 1 diabetes
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:12, s. 6305-6309
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Tidskriftsartikel (refereegranskat)abstract
- The GH-IGF-I axis is disturbed in patients with type 1 diabetes. Our aim was to investigate whether abnormalities are found in patients in very good glycemic control and, if so, to estimate the role of residual β-cell function. Patients with hemoglobin A 1c (HbA 1c) less than 6% (reference range, 3.6-5.4%) were selected for the study. Twenty-two men and 24 women, aged 41.3 ± 13.8 yr (mean ± SD), with a diabetes duration of 17.8 ± 14.6 yr participated. Healthy controls (15 women and nine men), aged 41.3 ± 13.0 yr, were also studied. Overnight fasting serum samples were analyzed for HbA 1c, C peptide, free and total IGFs, IGF-binding proteins (IGFBPs), GH-binding protein, and IGFBP-3 proteolysis. HbA 1c was 5.6 ± 0.5% in patients and 4.4 ± 0.3% in controls. Total IGF-I was 148 ± 7 μg/liter in patients and 178 ± 9 μg/liter in controls (P < 0.001). Free IGF-I, total IGF-II, IGFBP-3, and GH-binding protein were lower, whereas IGFBP-1, IGFBP-1-bound IGF-I, and IGFBP-2 were elevated compared with control values. Patients with detectable C peptide (≥100 pmol/liter) had higher levels of total IGF-I, free IGF-I, and total IGF-II and lower levels of IGFBP-1 and IGFBP-2 than those with an undetectable C peptide level despite having identical average HbA 1c. IGFBP-3 proteolysis did not differ between patients and controls. Despite very good glycemic control, patients with type 1 diabetes and no endogenous insulin production have low free and total IGF-I. Residual β-cell function, therefore, seems more important for the disturbances in the IGF system than good metabolic control per se, suggesting that portal insulin delivery is needed to normalize the IGF system.
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| 8. |
- Hedman, Christina, 1964-, et al.
(författare)
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The IGF-system is not affected by a twofold change in protein intake in patients with type 1 diabetes
- 2005
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 15:4, s. 304-310
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Tidskriftsartikel (refereegranskat)abstract
- Objective In type 1 diabetes the circulating IGF-system is altered with low IGF-I and changes in levels of IGF-binding proteins (IGFBPs) which may be of importance for the development of diabetes complications. Our aim was to study if IGF-I, as supported by experimental data in animals, can be affected by dietary protein intake.Design and methods Twelve patients with type 1 diabetes, age 37.5 ± 10.0 years (mean ± SD), diabetes duration 20.1 ± 9.3 years and HbA1c 6.3 ± 0.6% were allocated to isocaloric diets with either low normal protein content (LNP), (10 E%; 0.9 g protein/kg body weight) or high normal protein content (HNP) (20 E%; 1.8 g protein/kg body weight) in an open randomised cross-over study. Each diet was taken for 10 days with a wash-out period of 11 days in between. Circulating levels of total and free IGF-I and -II, IGFBP-1, -2 and -3 and GH-binding protein (GHBP) as well as ghrelin were measured with validated in-house immunoassays.Results At day 10, urinary urea excretion was 320 ± 75 mmol/24 h during LNP diet compared with 654 ± 159 mmol/24 h during HNP diet (p < 0.001). There were no changes in body weight or glycaemic control between the diets. Fasting levels of total IGF-I were 121 ± 33 μg/L after LNP and 117 ± 28 μg/L after HNP diet (ns) and the corresponding concentrations of IGFBP-1 were 142(141) and 132(157) μg/L [median (IQR)] (ns). There were no differences in plasma concentrations of total IGF-II, free IGF-I and -II, IGFBP-3, GHBP and ghrelin, whereas a small difference was found for IGFBP-2 (302 ± 97 vs. 263 ± 66 μg/L; LNP vs. HNP; p < 0.04).Conclusions A twofold change of the dietary protein intake does not influence the altered circulating IGF-system in type 1 diabetes. In order to affect the IGF-system other interventions must be used.
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| 9. |
- Hjort, Line, et al.
(författare)
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36 h fasting of young men influences adipose tissue DNA methylation of LEP and ADIPOQ in a birth weight-dependent manner
- 2017
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Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7075 .- 1868-7083. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Subjects born with low birth weight (LBW) display a more energy-conserving response to fasting compared with normal birth weight (NBW) subjects. However, the molecular mechanisms explaining these metabolic differences remain unknown. Environmental influences may dynamically affect epigenetic marks, also in postnatal life. Here, we aimed to study the effects of short-term fasting on leptin (LEP) and adiponectin (ADIPOQ) DNA methylation and gene expression in subcutaneous adipose tissue (SAT) from subjects with LBW and NBW. Methods: Twenty-one young LBW men and 18 matched NBW controls were studied during 36 h fasting. Eight subjects from each group completed a control study (overnight fast). We analyzed SAT LEP and ADIPOQ methylation (Epityper MassARRAY), gene expression (q-PCR), and adipokine plasma levels. Results: After overnight fast (control study), LEP and ADIPOQ DNA methylation levels were higher in LBW compared to those in NBW subjects (p ≤ 0.03) and increased with 36 h fasting in NBW subjects only (p ≤ 0.06). Both LEP and ADIPOQ methylation levels were positively associated with total body fat percentage (p ≤ 0.05). Plasma leptin levels were higher in LBW versus NBW subjects after overnight fasting (p = 0.04) and decreased more than threefold in both groups after 36 h fasting (p ≤ 0.0001). Conclusions: This is the first study to demonstrate that fasting induces changes in DNA methylation. This was shown in LEP and ADIPOQ promoters in SAT among NBW but not LBW subjects. The altered epigenetic flexibility in LBW subjects might contribute to their differential response to fasting, adipokine levels, and increased risk of metabolic disease.
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| 10. |
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