| 1. |
- Cooray, Gerald, et al.
(författare)
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Effects of intensified metabolic control on CNS function in type 2 diabetes
- 2011
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 36:1, s. 77-86
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Tidskriftsartikel (refereegranskat)abstract
- The mild cognitive decline associated with type 2 diabetes (T2DM) has been suggested to be reversible with improved glycemic control. In order to characterise this cognitive decline and study the effects of improved glycemic control we have studied patients with T2DM (N = 28) and healthy control subjects (N = 21). One group of patients with diabetes (N = 15) were given a 2-month treatment of intensified glycemic control, whereas the other group (N = 13) maintained their regular treatment.Cognitive function in four different domains, auditory event-related potentials (ERPs) and resting EEG power spectrum were studied in the two groups of patients and in healthy control subjects before and after the 2-month trial period.There were significant differences at baseline (p < 0.02) between patients with T2DM and controls. Patients had lower scores in two cognitive domains: verbal fluency (p < 0.01) and visuospatial ability (p < 0.03). T2DM also affected ERP with a decrease in N100 amplitude (p < 0.04) and an increase in P300 latency (p < 0.03). Furthermore, resting EEG activity in the beta band (13–30 Hz) was reduced (p < 0.04). The change between 1st and 2nd investigation was significantly different in the three groups of patients/subjects (p < 0.03). Patients receiving intensified treatment for glycemic control had an improvement of cognitive ability in visuospatial ability (p < 0.02) and semantic memory performance (p < 0.04) together with increased resting EEG activity in the alpha band (8–13 Hz, p < 0.02) and connectivity in the theta (4–8 Hz, p < 0.03) and alpha bands (p < 0.03) over central and lateral regions. Furthermore, there was an increase in the connectivity in the beta band (p < 0.04) over the central regions of the scalp.In conclusion, subjects with T2DM had a similar type of cognitive function impairment and EEG/ERP abnormality as previously demonstrated for subjects with type 1 diabetes (T1DM). Intensified therapy showed cognitive improvement not shown for regular treatment, suggesting that the negative effect of T2DM on cognition is reversible by means of improved glycemic control. Furthermore, there was an improvement in electro-physiological measures, suggesting increased availability of compensatory mechanisms in subjects with intensified treatment.
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| 2. |
- Fadl, Helena, 1965-, et al.
(författare)
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Changing diagnostic criteria for gestational diabetes in Sweden-a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol
- 2019
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Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden () is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches. Methods This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included. Discussion The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.
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| 3. |
- Gutefeldt, Kerstin, 1972-
(författare)
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Upper extremity impairments in type 1 diabetes in comparison to matched controls without diabetes : associations to the IGF-system, metabolic factors, disability and quality of life
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Compared with the general population, people with type 1 diabetes (T1D) more often exhibit pathological alterations in musculoskeletal tissue (impairments). Some of these impairments involve the upper extremities, i.e., the shoulders, hands, and fingers. Although present in diabetes, these complications are underdiagnosed and not actively searched for during routine clinical examinations. Furthermore, much is still unclear about these impairments, specifically regarding their etiology, risk factors, and consequences on daily life activities and quality of life. The growth hormone (GH)/insulinlike growth factor (IGF)-system is known to be affected in diabetes, but whether this is involved in upper extremity impairments (UEIs) is unclear. The aim of this thesis was to describe the prevalence of UEIs in patients with diabetes compared with controls. Furthermore, we aimed to search for risk factors of UEIs, and elucidate the impact of UEIs on daily life activities and health-related quality of life (HRQOL). We used two cohorts; the LedIG cohort (papers I–III), a large population-based study in which all patients with a long duration of T1D (>20 years), aged <67 years, living in the south-east region of Sweden were invited to participate, as well as matched controls without diabetes. This study was based on questionnaires as well as blood samples from the participants. The last paper (IV) included a smaller cohort (n=69) of patients with T1D, who both completed a questionnaire and were the subjects of a clinical examination.Paper I: The UEIs were common in diabetes, with a prevalence of up to 48%. Hand paresthesia was the most common impairment, followed by shoulder pain and stiffness. The prevalence of UEIs was 2–4 times higher in patients than in controls and was associated with more activity limitations. Risk factors were heterogeneous for the different UEIs and included female sex, increasing age, longer duration of diabetes, and poor glycemic control.Paper II: The GH-IGF-axis is important for the growth and function of musculoskeletal tissues. We examined differences in the IGF system between patients with T1D on subcutaneous insulin treatment and controls. We found lower levels of IGF-I and insulinlike growth factor-binding protein (IGFBP)-3 and higher levels of GH and IGFBP-1 in patients with T1D than in controls. The largest difference was found in IGFBP-1, and this probably reflected insulin deficiency. The IGF-I levels were increased with increasing insulin doses. However, even at very high insulin doses (>1 U/kg) the IGF-I Z-score was subnormal, indicating that IGF-I cannot be normalized by subcutaneous insulin treatment. Residual endogenous insulin secretion counteracted these alterations. Furthermore, we investigated possible relationships between UEIs and IGF-I, and found no association.Paper III: The HRQOL was lower in patients with T1D than in controls. Patients with shoulder impairments, hand paresthesia, and hand stiffness, but not finger impairments, had lower HRQOL scores than patients without these impairments. The patients with T1D showed a higher frequency of sick leave than controls, and a common reason for this was musculoskeletal impairments.Paper IV: In addition to the self-reported UEIs, the prevalence of UEIs was also investigated by clinical examination. Clinical UEIs were found in 65% of the participants, with shoulder test (hands against back), prayer sign test, and the Phalen’s and Tinel’s tests being most prevalent. We compared self-reported UEIs to clinical UEIs and found that self-reported impairments were associated with clinical examination. We also found that self-reported shoulder impairments, reduced hand strength, and previous surgery for carpal tunnel syndrome and trigger finger were associated with several other UEIs.In current diabetic care, there is no established routine to capture UEIs, as opposed to other known diabetes complications. We show that UEIs are more common in patients with T1D than in controls, and that they are related to impaired HRQOL and daily life activity limitations. Clinical routines including self-reported UEIs, e.g. shoulder stiffness and reduced hand strength, might be used to identify patients with UEIs in need of clinical investigation, enhanced preventive and therapeutic strategies, as well as rehabilitative interventions.
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| 4. |
- Nygren, J, et al.
(författare)
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Disturbed anabolic hormonal patterns in burned patients : the relation to glucagon
- 1995
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Ingår i: Clinical Endocrinology. - : Wiley-Blackwell Publishing Inc.. - 0300-0664 .- 1365-2265. ; 43:4, s. 491-500
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Complex changes in the anabolic regulators of metabolism occur after major injury. We have studied the time course for IGF-I and IGFBP-1 after burn injury and their relations to circulating levels of other anabolic and catabolic hormones. The hormonal patterns during the onset of sepsis were also investigated. Patients. Eight patients (age 36 (6) years, mean (SEM)) with major burn injury (burn area 42 (6)%) were studied. The first 2 days since the burn were used for rehydration therapy (rehydration period), after which a complete total parenteral nutrition (TPN) period was initiated. Seven of the eight patients developed sepsis, confirmed with positive blood cultures, during the study period. Six of the eight survived. Measurements. The hormonal changes determined inthe morning during the first 7 days after the burn and from day 22 to 24 were investigated. The superimposed effects of sepsis were studied by normalizing all data to the day of positive blood cultures and clinical onset of sepsis. Results. On admission, plasma levels of glucagon, IGFBP-1 and GH were elevated while levels of IGF-I were low. During the first week after the burn, morning levels of glucagon and insulin increased while levels of GH and IGF-I decreased. GH levels were still elevated compared to healthy subjects. Despite the increase in insulin levels, IGFBP-1 remained elevated. Three weeks after the burn injury, IGF-I levels were increased but still markedly below normal, while IGFBP-1 levels remained unchanged. Persistent elevations of insulin levels were combined with reductions in glucagon levels. Admission levels of IGFBP-1 correlated to nitrogen loss (negative nitrogen balance) during the first 24 hours after the burn (r = 0.84, P < 0.05). A correlation between negative nitrogen balance and glucagon levels was found during the early catabolic period in the rehydration period (i.e. days 2-3, r = 0.84, P < 0.01). The relative change in IGFBP-1 levels in the rehydration period correlated to changes in glucagon levels (days 2-3 vs admission, r = 0.65, P < 0.05). The insulin/glucagon molar ratio correlated to the IGF-I/IGFBP-1 ratio during both the rehydration period (days 2-3, r = 0.77, P < 0.05) and the third week after the burn (r = 0.77, P < 0.05). During the most catabolic phase in the first week after the burn (TPN period) there was an inverse relation between IGF-I and IGFBP-1 levels (r = -0.83, P < 0.05). During the less catabolic third week after the burn, an inverse correlation was found between IGF-I and glucagon (r = -0.83, P < 0.05). Sepsis, superimposed upon the burn trauma, was associated with transient elevations in IGFBP-1 and reductions in insulin despite elevated levels of glucose and a further 50% increase in nitrogen losses. Conclusions. The present findings show that marked changes in important anabolic regulating factors occur after major burn injury. Uncoupling of the GH-IGF-I axis, and the attenuation of the inhibitory effects of insulin on IGFBP-1, both contribute to the reduction in IGF-I levels and bioavailability, factors which may play an important role in post injury metabolism. Furthermore, these data suggest that of the catabolic hormones (catecholamines, cortisol and glucagon), primarily glucagon seem to be involved in the modulation of IGF-I and IGFBP-1 levels following burn injury.
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| 5. |
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| 6. |
- Olausson, Hanna, et al.
(författare)
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Maternal food restriction during gestation elevates insulin-like growth factor I and insulin-like growth factor binding protein 1 in adult male rat offspring
- 2006
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Ingår i: Nutrition Research. - : Elsevier BV. - 0271-5317 .- 1879-0739. ; 26:7, s. 350-355
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Tidskriftsartikel (refereegranskat)abstract
- Low birth weight due to maternal malnutrition is associated with increased risk of developing diseases in adulthood, for example, cardiovascular disease. Postnatal oxytocin treatment has previously been shown to have positive effects on blood pressure and corticosterone levels in adult offspring from malnourished dams. The aims of this study were to investigate if maternal food restriction during gestation alters plasma levels of insulin-like growth factor I (IGF-I), IGF binding protein 1 (IGFBP-1), glucose, and insulin in adult male rat offspring, and if postnatal oxytocin treatment has any effect on those changes. Adult offspring from food-restricted mothers had increased levels of IGF-I and IGFBP-1 compared with ad libitum–fed offspring. Postnatal oxytocin treatment had no effect on the IGF system in adulthood. In conclusion, maternal malnutrition during gestation altered the IGF system in adult rat offspring.
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| 7. |
- Sohlström, Annica, 1959-, et al.
(författare)
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Oxytocin treatment during early life influences reproductive performance in ad libitum fed and food-restricted female rats
- 2002
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Ingår i: Biology of the Neonate. - : S. Karger AG. - 0006-3126 .- 1421-9727. ; 81:2, s. 132-138
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Tidskriftsartikel (refereegranskat)abstract
- Oxytocin treatment may permanently alter endocrine axes resulting in anti-stress and anabolic effects. However, the nutritional status influences the effects of oxytocin. The specific aims of this study were to investigate the effects of postnatal oxytocin treatment on reproductive performance in adult life, by studying maternal weight gain, adiposity, plasma levels of IGF-I as well as fetal and placental weights in the following groups of animals: (1) Ad libitum fed dams coming from ad libitum fed mothers. (2) Ad libitum fed dams coming from food-restricted mothers. (3) Food-restricted dams coming from ad libitum fed mothers. (4) Food-restricted dams coming from food-restricted mothers. Oxytocin treatment postnatally had long-term effects and increased adiposity in pregnant dams and stimulated placental and fetal growth relative to saline-treated dams. However, if the dams themselves had been exposed to food restriction during fetal life, the effect of postnatal oxytocin treatment changed. The oxytocin-treated mothers were still fatter but had smaller fetuses. In conclusion, postnatal oxytocin treatment influences reproductive performance in later life but is dependent on the mother’s previous and current nutritional experience.
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| 8. |
- Alehagen, Urban, et al.
(författare)
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Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens
- 2017
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. Methods 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. Findings After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P amp;gt; 0.0001), IGF-1 SD score (F = 29; P amp;lt; 0.0001) and of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme Q10 also on the expression of IGF-1 as one of the mechanistic effects of the intervention. Conclusion Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of intervention with selenium and coenzyme Q10 is needed.
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| 9. |
- Alehagen, Urban, et al.
(författare)
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Selenium and Coenzyme Q10 Supplementation Improves Renal Function in Elderly Deficient in Selenium : Observational Results and Results from a Subgroup Analysis of a Prospective Randomised Double-Blind Placebo-Controlled Trial
- 2020
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- A low selenium intake is found in European countries, and is associated with increased cardiovascular mortality. There is an association between selenium level and the severity of kidney disease. An association between inflammation and selenium intake is also reported. The coenzyme Q10 level is decreased in kidney disease. The aim of this study was to examine a possible association between selenium and renal function in an elderly population low in selenium and coenzyme Q10, and the impact of intervention with selenium and coenzyme Q10 on the renal function. The association between selenium status and creatinine was studied in 589 elderly persons. In 215 of these (mean age 71 years) a randomised double-blind placebo-controlled prospective trial with selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 117) or placebo (n = 98) was conducted. Renal function was determined using measures of glomerular function at the start and after 48 months. The follow-up time was 5.1 years. All individuals were low on selenium (mean 67 μg/L (SD 16.8)). The changes in renal function were evaluated by measurement of creatinine, cystatin-C, and the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) algorithm, and by the use of T-tests, repeated measures of variance and ANCOVA analyses. An association between low selenium status and impaired renal function was observed. Intervention causes a significantly lower serum creatinine, and cystatin-C concentration in the active treatment group compared with those on placebo (p = 0.0002 and p = 0.001 resp.). The evaluation with CKD-EPI based on both creatinine and cystatin-C showed a corresponding significant difference (p < 0.0001). All validations showed corresponding significant differences. In individuals with a deficiency of selenium and coenzyme Q10, low selenium status is related to impaired renal function, and thus supplementation with selenium and coenzyme Q10 results in significantly improved renal function as seen from creatinine and cystatin-C and through the CKD-EPI algorithm. The explanation could be related to positive effects on inflammation and oxidative stress as a result of the supplementation.
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| 10. |
- Andreasson, Anna Nixon, et al.
(författare)
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Leptin and adiponectin : Distribution and associations with cardiovascular risk factors in men and women of the general population
- 2012
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Ingår i: American Journal of Human Biology. - : Wiley. - 1042-0533 .- 1520-6300. ; 24:5, s. 595-601
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In view of the increasing prevalence of obesity worldwide, understanding the role of the recently discovered adipokines leptin and adiponectin is of high clinical relevance. The aim of the present study was to assess the association between levels of leptin and adiponectin with age, known cardiovascular risk factors and to establish whether there are differences between men and women of the general population.METHODS: A total of 98 men and 107 women of the general population, aged between 20 and 74 years, underwent a medical examination at a clinical research center and fasting morning blood samples were also taken.RESULTS: Leptin (mean 7.5 μg l(-1) in men and 16.0 μg l(-1) in women) and adiponectin (mean 7.3 mg l(-1) in men and 11.9 mg l(-1) in women) levels were higher in women than men (Ps < 0.001). Both leptin and adiponectin levels increased with advancing age in both men and women (Ps < 0.05). Leptin was highly associated with factors for metabolic syndrome in men while in women, leptin was highly associated with inflammatory factors. Adiponectin was associated with blood lipids in both men and women, and glucose homeostasis more in women than in men.CONCLUSIONS: Leptin and adiponectin levels were ∼2 times and 1.5 times higher in women than in men, respectively. In addition, although leptin and adiponectin were associated to CVD risk factors in both men and women, we observed differences in specific CVD risk factor groups between men and women. These differences may be due to different regulatory mechanisms and effects of these adipokines in men and women.
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| 11. |
- Bang, Peter, et al.
(författare)
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Free dissociable IGF-I : Association with changes in IGFBP-3 proteolysis and insulin sensitivity after surgery
- 2016
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Ingår i: Clinical Nutrition. - : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 35:2, s. 408-413
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients receiving a carbohydrate drink (CHO) before major abdominal surgery display improved insulin sensitivity postoperatively and increased proteolysis of IGFBP-3 (IGFBP-3-PA) compared to patients undergoing similar surgery after overnight fasting. Aims: We hypothesized that serum IGFBP-3-PA increases bioavailability of circulating IGF-I and preserves insulin sensitivity in patients given CHO. Design: Matched control study. Methods: At Karolinska University Hospital, patients given CHO before major elective abdominal surgery (CHO,n = 8) were compared to patients undergoing similar surgical procedures after overnight fasting (FAST,n = 10). Results from two different techniques for determination of free-dissociable IGF-I (fdIGF-I) were compared with changes in IGFBP-3-PA and insulin sensitivity. Results: Postoperatively, CHO displayed 18% improvement in insulin sensitivity (hyperinsulinemic clamp) and increased IGFBP-3-PA vs. FAST. As determined by IRMA, fdIGF-I increased by 48 +/- 25% in CHO while fdIGF-I decreased by 13 +/- 18% in FAST (p < 0.01 vs. CHO, when corrected for duration of surgery). However, fdIGF-I determined by ultra-filtration decreased similarly in both groups (-22 +/- 8% vs. -25 +/- 8%, p = 0.8) and IGFBP-1 increased similarly in both groups. Patients with less insulin resistance after surgery demonstrated larger increases in fdIGF-I by IRMA (r = 0.58, p < 0.05). Fifty-three % of the variability of the changes in fdIGF-I by IRMA could be explained by changes in IGFBP-3-PA and total IGF-I levels (p < 0.05), while IGFBP-1 did not contribute significantly. Conclusion: During conditions when serum IGF-I bioavailability is regulated by IGFBP-3 proteolysis, measurements of fdIGF-I by IRMA is of physiological relevance as it correlates with the associated changes in insulin sensitivity.
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| 12. |
- Bennet, Anna M, et al.
(författare)
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The risk of myocardial infarction is enhanced by a synergistic interaction between serum insulin and smoking.
- 2002
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 147:5, s. 641-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the relationship between levels of serum insulin, the homeostasis model assessment (HOMA) and IGF-binding protein-1 (IGFBP-1) as factors related to myocardial infarction (MI) risk, and their interaction with lifestyle-related risk factors. DESIGN: The Stockholm epidemiology programme (SHEEP), a case-control study, consisting of 749 first-time MI cases (510 men, 239 women) and 1101 healthy controls (705 men, 396 women) was used. METHODS: The risk of developing MI was assessed by calculating odds ratios (OR) and synergistic interactions (SI) between serum insulin, IGFBP-1, HOMA and other variables related to MI risk (including smoking) in men and women. RESULTS: Subjects with elevated levels of insulin and HOMA (>75th percentile) had increased MI risks when compared with individuals with low levels. ORs for elevated insulin and HOMA (adjusted for age and residential area) for men: insulin 1.6 (95% confidence interval (CI) 1.3-2.1) and HOMA 1.5 (95% CI 1.1-1.9) and for women: insulin 2.1 (95% CI 1.5-2.9) and HOMA 1.9 (95% CI 1.3-2.8). Women with low levels of IGFBP-1 (<10th percentile) showed a tendency towards elevated MI risk even if this was not statistically significant (OR 1.5 (95% CI 0.9-2.6)). Smokers with high levels of serum insulin had greatly increased MI risk (OR for men: 4.7 (95% CI 3.0-7.2) and OR for women: 8.1 (95% CI 4.5-14.8)). SI scores based upon these interactions were statistically significant. CONCLUSIONS: These results might have preventive cardiovascular implications as they clearly suggest that subjects with insulin resistance are particularly susceptible to the hazards of smoking.
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| 13. |
- Bennet, Louise, et al.
(författare)
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BMI and waist circumference cut-offs for corresponding levels of insulin sensitivity in a Middle Eastern immigrant versus a native Swedish population - The MEDIM population based study
- 2016
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to identify corresponding body mass index (BMI) and waist circumference cut-offs for equivalent levels of insulin sensitivity in a Middle Eastern immigrant population compared with native Swedes. Methods: Citizens of Malmö, Sweden aged 30 to 75 years, who were born in Iraq or Sweden, were in 2010-2012 invited to participate in a health examination including anthropometrics, oral glucose tolerance test, fasting samples and interviews concerning sociodemographic factors and lifestyle behaviours. Results: In total, 1176 individuals born in Iraq and 688 born in Sweden, without previously diagnosed type 2 diabetes, participated in the study. In normal weight participants (BMI < 25 kg/m2), 21.2% of Iraqis vs 9.3% of Swedes were insulin resistant. Corresponding figures in participants without abdominal obesity (waist circumference, men < 94 cm, women < 80 cm) were 28.2% of Iraqis vs 9.4% of Swedes. The age-adjusted insulin sensitivity index (ISI) for obese Swedes (BMI 30 kg/m2) corresponded in Iraqi men with BMI of 28.5 kg/m2, and in Iraqi women with BMI of 27.5 kg/m2. The ISI level in abdominally obese Swedes corresponded with waist circumference cut-offs of 84.0 cm and 71.0 cm in Iraqi men and women, respectively. In men only, larger waist circumference (P interaction = 0.026) presented a stronger association with impaired ISI in Iraqis as compared to Swedes. Conclusions: Our data shows that the impact of BMI and waist circumference on ISI is ethnic- and gender-specific, indicating a disturbed fat metabolism in Iraqi males in particular. Our data suggests that 10 cm lower cut-off values for abdominal obesity, than is currently recommended by major organisations, should be considered when estimating diabetes risk in Middle Eastern populations.
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| 14. |
- Bentinger, Magnus, et al.
(författare)
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Effects of various squalene epoxides on coenzyme Q and cholesterol synthesis
- 2014
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981 .- 1879-2618. ; 1841:7, s. 977-986
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Tidskriftsartikel (refereegranskat)abstract
- 2,3-Oxidosqualene is an intermediate in cholesterol biosynthesis and 2,3:22,23-dioxidosqualene act as the substrate for an alternative pathway that produces 24(S),25-epoxycholesterol which effects cholesterol homeostasis. In light of our previous findings concerning the biological effects of certain epoxidated all-trans-polyisoprenes, the effects of squalene carrying epoxy moieties on the second and third isoprene residues were investigated here. In cultures of HepG2 cells both monoepoxides of squalene and one of their hydrolytic products inhibited cholesterol synthesis and stimulated the synthesis of coenzyme Q (CoQ). Upon prolonged treatment the cholesterol content of these cells and its labeling with [H-3]mevalonate were reduced, while the amount and labeling of CoQ increased. Injection of the squalene monoepoxides into mice once daily for 6 days elevated the level of CoQ in their blood, but did not change the cholesterol level. The same effects were observed upon treatment of apoE-deficient mice and diabetic GK-rats. This treatment increased the hepatic level of CoQ10 in mice, but the amount of CoQ9, which is the major form, was unaffected. The presence of the active compounds in the blood was supported by the finding that cholesterol synthesis in the white blood cells was inhibited. Since the ratio of CoQ9/CoQ10 varies depending on the experimental conditions, the cells were titrated with substrate and inhibitors, leading to the conclusion that the intracellular isopentenyl-PP pool is a regulator of this ratio. Our present findings indicate that oxidosqualenes may be useful for stimulating both the synthesis and level of CoQ both in vitro and in vivo.
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| 15. |
- Bentinger, Magnus, et al.
(författare)
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Influence of liver-X-receptor on tissue cholesterol, coenzyme Q and dolichol content
- 2012
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Ingår i: Molecular membrane biology. - : Informa UK Limited. - 0968-7688 .- 1464-5203. ; 29:7, s. 299-308
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Tidskriftsartikel (refereegranskat)abstract
- The organ content of the mevalonate pathway lipids was investigated in liver-X-receptor (LXR) alpha, beta and double knockout 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 LXR alpha 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.
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| 16. |
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| 17. |
- Bentinger, Magnus, et al.
(författare)
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Stimulation of coenzyme Q synthesis.
- 2008
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Ingår i: Biofactors. - : Wiley. - 0951-6433 .- 1872-8081. ; 32:1-4, s. 99-111
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Tidskriftsartikel (refereegranskat)
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| 18. |
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| 19. |
- Ehrsson, Ylva Tiblom, et al.
(författare)
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Explorative study on the predictive value of systematic inflammatory and metabolic markers on weight loss in head and neck cancer patients undergoing radiotherapy
- 2010
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Ingår i: Supportive Care in Cancer. - : Springer Science and Business Media LLC. - 0941-4355 .- 1433-7339. ; 18:11, s. 1385-1391
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Tidskriftsartikel (refereegranskat)abstract
- Purpose This study aimed to explore the predictive value of systematic inflammatory and metabolic markers in head and neck (H&N) cancer patients during radiotherapy (RT). Methods Twenty-seven patients were evaluated. The protocol included serial blood tests [highly sensitive C-reactive protein (hsCRP), albumin, insulin-like growth factor 1 (IGF-1), IGF binding protein 1 (IGFBP-1) and ghrelin], measurements of body weight and assessment of oral mucositis. Results The mean nadir of weight loss was observed at the end of RT. At the time of diagnosis, mean hsCRP was 5.2 +/- 1.0 mg/L. HsCRP significantly increased during RT and decreased during the post-RT period. Mean maximum hsCRP was 35.8 +/- 8.5 mg/L, with seven patients reaching >40 mg/L. A numerical decrease of albumin (by 18.2%) and only small changes in IGF-1, IGFBP-1 and ghrelin levels were observed. None of the metabolic parameters was significantly associated with weight loss. Conclusions HsCRP increased in response to RT for H&N cancer as a sign of irradiation-induced inflammation. Weight loss was not preceded by changes of the metabolic parameters, indicating that assessment of the blood markers used in this study is of little value. Regular body weight measurement and assessment of oral mucositis are feasible, cheap and important procedures to control the metabolic homeostasis during RT.
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| 21. |
- Ekström, Eva-Charlotte, et al.
(författare)
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Effects of prenatal micronutrient and early food supplementation on metabolic status of the offspring at 4.5 years of age. The MINIMat randomized trial in rural Bangladesh.
- 2016
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 45:5, s. 1656-1667
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fetal nutritional insults may alter the later metabolic phenotype. We hypothesized that early timing of prenatal food supplementation and multiple micronutrient supplementation (MMS) would favourably influence childhood metabolic phenotype.METHODS: Pregnant women recruited 1 January to 31 December 2002 in Matlab, Bangladesh, were randomized into supplementation with capsules of either 30 mg of iron and 400 μg of folic acid, 60 mg of iron and 400 μg of folic acid, or MMS containing a daily allowance of 15 micronutrients, and randomized to food supplementation (608 kcal) either with early invitation (9 weeks' gestation) or usual invitation (at 20 weeks). Their children (n = 1667) were followed up at 4.5 years with assessment of biomarkers of lipid and glucose metabolism, inflammation and oxidative stress.RESULTS: Children in the group with early timing of food supplementation had lower cholesterol (difference -0.079 mmol/l, 95% confidence interval (CI) -0.156; -0.003), low-density lipoprotein (LDL) (difference -0.068 mmol/l, 95% CI -0.126; -0.011) and ApoB levels (difference -0.017 g/l, 95% CL -0.033; -0.001). MMS supplementation resulted in lower high-density lipoprotein (HDL) (difference -0.028 mmol/l, 95% CL -0.053; -0.002), lower glucose (difference -0.099 mmol/l, 95% CL -0.179; -0.019) and lower insulin-like growth factor 1 (IGF-1) (difference on log scale -0.141 µg/l, 95% CL -0.254; -0.028) than 60 mg iron and 400 μg folic acid. There were no effects on markers of inflammation or oxidative stress.CONCLUSIONS: Findings suggest that in a population where malnutrition is prevalent, nutrition interventions during pregnancy may modify the metabolic phenotype in the young child that could have consequences for later chronic disease risks.
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| 23. |
- Engvall, Inga-Lill, et al.
(författare)
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Impact of low-dose prednisolone on bone synthesis and resorption in early rheumatoid arthritis: experiences from a two-year randomized study
- 2008
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Patients with rheumatoid arthritis (RA) have an increased frequency of osteoporosis, mainly because of increased bone resorption. Reduction of disease activity is suggested to reduce bone remodelling. It might also be possible that prednisolone treatment could cause this effect because prednisolone has been shown to arrest the development of joint destruction in early RA. Therefore, we examined the effects of low-dose prednisolone on serum concentrations of bone remodelling markers and insulin-like growth factor-1 (IGF-1) in RA patients in relation to bone mineral density. Methods One hundred and fifty patients, 67% women, with early RA, mean disease duration of six months (95% confidence interval (CI) = three to eight months), who had participated in the BARFOT (Better Anti-Rheumatic FarmacOTherapy) low-dose prednisolone study were included. They had been randomised to either the P-group, who were treated with 7.5 mg prednisolone daily (n = 70, mean age = 51 years, 95% CI 48 to 54 years), or the NoP-group, who received no prednisolone (n = 80, mean age 58 years, 95% CI 56 to 61 years), when they started their first disease-modifying anti-rheumatic drug (DMARD). Serum samples were analysed at baseline, 3 and 12 months for procollagen type I N-terminal propeptide (P1NP), a marker of bone formation, and the C-telopeptide crosslaps of type I collagen (CTX-1) and C-terminal telopeptide of type I collagen (1CTP), markers of bone degradation. IGF-1 was analysed at baseline and after 12 months. Bone mineral density at the lumbar spine and femoral neck was assessed by dual-energy X-ray absorptiometry at baseline and after 24 months. Results Levels of P1NP decreased rapidly in the P-group (p < 0.001). Levels of CTX-1 and 1CTP decreased in both treatment groups, but significantly more in the P-group (differences between groups p < 0.019 and p < 0.001, respectively). IGF-1 increased in the P-group (p < 0.001) but remained stable in the NoP-group. Bone mineral density decreased in the spine in both groups, significantly more in postmenopausal women from the P-group. Femur bone mineral density only decreased in the NoP-group. Conclusions Low-dose prednisolone in early RA counteracts the negative impact of rheumatoid inflammation on bone tissue in the hip, a juxta-articular localisation. Thus bone mineral density was preserved in the femur in the P-group and 1CTP decreased rapidly. However, the systemic inflammatory consequences on bone could not be prevented in the lumbar spine, especially not in postmenopausal women, probably because of the combined effect of suppression of bone synthesis by prednisolone and the postmenopausal status.
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| 24. |
- Falhammar, Henrik, et al.
(författare)
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Bone Mineral Density, Bone Markers, and Fractures in Adult Males with Congenital Adrenal Hyperplasia.
- 2013
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 168, s. 331-341
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to determine bone mineral density (BMD), markers of bone metabolism, fractures, and steroids reflecting hormonal control in adult males with congenital adrenal hyperplasia (CAH). SUBJECTS, METHODS AND DESIGN: We compared CAH males with 21-hydroxylase deficiency (n=30), 19-67 years old, with age- and sex-matched controls (n=32). Subgroups of CYP21A2 genotypes, age, glucocorticoid preparation, poor control versus overtreatment, and early versus late (>36 months) diagnosis were studied. Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) and markers of bone metabolism and androgens/17-hydroxyprogesterone levels were investigated. RESULTS: All, including older (>30 yrs), CAH patients had lower BMD in all measured sites compared to control subjects. The null group demonstrated lower BMD in more locations than the other groups. Osteoporosis/osteopenia was present in 81% of CAH patients compared to 32% in controls (≥30 yrs). Fracture frequency was similar, osteocalcin lower, and fewer patients than controls had vitamin D insufficiency. IGF-I was elevated in the milder genotypes. In patients, total body BMD was positively correlated to weight, BMI, total lean body mass, triglycerides, and negatively to prolactin. Patients on prednisolone had lower BMD and osteocalcin levels than those on hydrocortisone/cortisone acetate. Patients with poor control had higher femoral neck BMD. There were no differences in BMD between patients with an early versus late diagnosis. CONCLUSIONS: CAH males have low BMD and bone formation markers. BMD should be monitored, adequate prophylaxis and treatment established, and glucocorticoid doses optimized to minimize the risk of future fractures.
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| 25. |
- Gu, Tianwei, et al.
(författare)
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IGF2BP2 and IGF2 genetic effects in diabetes and diabetic nephropathy
- 2012
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Ingår i: Journal of diabetes and its complications. - : Elsevier BV. - 1056-8727 .- 1873-460X. ; 26:5, s. 393-398
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The IGF2BP2 gene is located on chromosome 3q27.2 within a region linked to type 1 diabetes (T1D), type 2 diabetes (120) and diabetic nephropathy (ON). Its protein functionally binds to 5'-UTR of the imprinting IGF2 gene. The present study aims to evaluate the IGF2BP2-IGF2 genetic effects in diabetes and DN. Materials and Methods: Three cohorts including T1D with and without DN (n = 1139) of European descents from the GoKinD study, Swedish T1D with and without ON (n = 303) and Czech control subjects without diabetes, T1D, T2D with and without ON (n = 1418) were enrolled in TaqMan genotyping experiments for IGF2BP2 rs4402960 and IGF2 rs10770125. Igf2bp2 gene expression in kidney tissues of db/db and control mice at the ages of 5 and 26 weeks was examined with real time RT-PCR and Western blot. Results: An association of IGF2BP2 rs4402960 with T2D in the Czech population was replicated. This IGF2BP2 polymorphism (P = 0.037, OR = 0.69 95% CI 0.49-0.98) was found to be associated with DN in male not in female patients with T1D selected from the GoKinD study. In the analyses of combined the GoKinD, Czech and Swedish populations, the association between IGF2BP2 polymorphism and ON in male patients with T1D was still significant (P = 0.030, OR = 0.73, 95% CI 0.54-0.97). IGF2 rs10770125 was also associated with DN in male T1D patients of the GoKinD population (P = 0.038, OR = 0.67 95% CI 0.46-0.98). There might be a genetic interaction between IGF2BP2 and IGF2 (P = 0.05). The Igf2bp2 gene expression levels were increased in the kidneys of db/db mice compared to controls at the age of 5 weeks but not at 26 weeks. Conclusions: The present study has replicated the association of IGF2BP2 rs4402960 with T2D in the Czech population and provided data suggesting that IGF2BP2 may have genetic interaction with IGF2 with a protective effect against DN in male patients with T1D. (C) 2012 Elsevier Inc. All rights reserved.
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