1. |
- Cooray, Gerald, et al.
(author)
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Effects of intensified metabolic control on CNS function in type 2 diabetes
- 2011
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 36:1, s. 77-86
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Journal article (peer-reviewed)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.
(author)
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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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In: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
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Journal article (peer-reviewed)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-
(author)
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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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Doctoral thesis (other academic/artistic)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.
(author)
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Disturbed anabolic hormonal patterns in burned patients : the relation to glucagon
- 1995
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In: Clinical Endocrinology. - : Wiley-Blackwell Publishing Inc.. - 0300-0664 .- 1365-2265. ; 43:4, s. 491-500
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Journal article (peer-reviewed)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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6. |
- Olausson, Hanna, et al.
(author)
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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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In: Nutrition Research. - : Elsevier BV. - 0271-5317 .- 1879-0739. ; 26:7, s. 350-355
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Journal article (peer-reviewed)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.
(author)
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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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In: Biology of the Neonate. - : S. Karger AG. - 0006-3126 .- 1421-9727. ; 81:2, s. 132-138
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Journal article (peer-reviewed)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.
(author)
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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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In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:6
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Journal article (peer-reviewed)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.
(author)
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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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In: Nutrients. - : MDPI AG. - 2072-6643. ; 12:12
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Journal article (peer-reviewed)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.
(author)
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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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In: American Journal of Human Biology. - : Wiley. - 1042-0533 .- 1520-6300. ; 24:5, s. 595-601
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Journal article (peer-reviewed)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.
(author)
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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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In: Clinical Nutrition. - : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 35:2, s. 408-413
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Journal article (peer-reviewed)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.
(author)
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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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In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 147:5, s. 641-7
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Journal article (peer-reviewed)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.
(author)
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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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In: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 16:1
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Journal article (peer-reviewed)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.
(author)
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Effects of various squalene epoxides on coenzyme Q and cholesterol synthesis
- 2014
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In: 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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Journal article (peer-reviewed)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.
(author)
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Influence of liver-X-receptor on tissue cholesterol, coenzyme Q and dolichol content
- 2012
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In: Molecular membrane biology. - : Informa UK Limited. - 0968-7688 .- 1464-5203. ; 29:7, s. 299-308
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Journal article (peer-reviewed)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.
(author)
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Stimulation of coenzyme Q synthesis.
- 2008
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In: Biofactors. - : Wiley. - 0951-6433 .- 1872-8081. ; 32:1-4, s. 99-111
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Journal article (peer-reviewed)
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18. |
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19. |
- Ehrsson, Ylva Tiblom, et al.
(author)
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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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In: Supportive Care in Cancer. - : Springer Science and Business Media LLC. - 0941-4355 .- 1433-7339. ; 18:11, s. 1385-1391
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Journal article (peer-reviewed)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.
(author)
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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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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 45:5, s. 1656-1667
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Journal article (peer-reviewed)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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22. |
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23. |
- Engvall, Inga-Lill, et al.
(author)
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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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In: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 10:6
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Journal article (peer-reviewed)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.
(author)
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Bone Mineral Density, Bone Markers, and Fractures in Adult Males with Congenital Adrenal Hyperplasia.
- 2013
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In: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 168, s. 331-341
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Journal article (peer-reviewed)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.
(author)
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IGF2BP2 and IGF2 genetic effects in diabetes and diabetic nephropathy
- 2012
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In: Journal of diabetes and its complications. - : Elsevier BV. - 1056-8727 .- 1873-460X. ; 26:5, s. 393-398
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Journal article (peer-reviewed)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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26. |
- Heneen, Waheeb K., et al.
(author)
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Fusion of oil bodies in endosperm of oat grains
- 2008
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In: Planta. - : Springer Science and Business Media LLC. - 0032-0935 .- 1432-2048. ; 228:4, s. 589-599
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Journal article (peer-reviewed)abstract
- Few microscopical studies have been made on lipid storage in oat grains, with variable results as to the extent of lipid accumulation in the starchy endosperm. Grains of medium- and high-lipid oat (Avena sativa L.) were studied at two developmental stages and at maturity, by light microscopy using different staining methods, and by scanning and transmission electron microscopy. Discrete oil bodies occurred in the aleurone layer, scutellum and embryo. In contrast, oil bodies in the starchy endosperm often had diffuse boundaries and fused with each other and with protein vacuoles during grain development, forming a continuous oil matrix between the protein and starch components. The different microscopical methods were confirmative to each other regarding the coalescence of oil bodies, a phenomenon probably correlated with the reduced amount of oil-body associated proteins in the endosperm. This was supported experimentally by SDS-PAGE separation of oil-body proteins and immunoblotting and immunolocalization with antibodies against a 16 kD oil-body protein. Much more oil-body proteins per amount of oil occurred in the embryo and scutellum than in the endosperm. Immunolocalization of 14 and 16 kD oil-body associated proteins on sectioned grains resulted in more heavy labeling of the embryo, scutellum and aleurone layer than the rest of the endosperm. Observations on the appearance of oil bodies at an early stage of development pertain to the prevailing hypotheses of oil-body biogenesis.
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28. |
- Heneen, Waheeb, et al.
(author)
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Seed colour loci, homoeology and linkage groups of the C genome chromosomes revealed in Brassica rapa - B. oleracea monosomic alien addition lines
- 2012
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In: Annals of Botany. - : Oxford University Press (OUP). - 0305-7364 .- 1095-8290. ; 109, s. 1227-1242
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Journal article (peer-reviewed)abstract
- Background and Aims Brassica rapa and B. oleracea are the progenitors of oilseed rape B. napus. The addition of each chromosome of B. oleracea to the chromosome complement of B. rapa results in a series of monosomic alien addition lines (MAALs). Analysis of MAALs determines which B. oleracea chromosomes carry genes controlling specific phenotypic traits, such as seed colour. Yellow-seeded oilseed rape is a desirable breeding goal both for food and livestock feed end-uses that relate to oil, protein and fibre contents. The aims of this study included developing a missing MAAL to complement an available series, for studies on seed colour control, chromosome homoeology and assignment of linkage groups to B. oleracea chromosomes. † Methods A new batch of B. rapa–B. oleracea aneuploids was produced to generate the missing MAAL. Seed colour and other plant morphological features relevant to differentiation of MAALs were recorded. For chromosome characterization, Snow’s carmine, fluorescence in situ hybridization (FISH) and genomic in situ hybridization (GISH) were used. † Key Results The final MAAL was developed. Morphological traits that differentiated the MAALs comprised cotyledon number, leaf morphology, flower colour and seed colour. Seed colour was controlled by major genes on two B. oleracea chromosomes and minor genes on five other chromosomes of this species. Homoeologous pairing was largely between chromosomes with similar centromeric positions. FISH, GISH and a parallel microsatellite marker analysis defined the chromosomes in terms of their linkage groups. †Conclusions A complete set of MAALs is now available for genetic, genomic, evolutionary and breeding perspectives. Defining chromosomes that carry specific genes, physical localization of DNA markers and access to established genetic linkage maps contribute to the integration of these approaches, manifested in the confirmed correspondence of linkage groups with specific chromosomes. Applications include marker-assisted selection and breeding for yellow seeds.
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29. |
- Irving, Gerd Faxén, et al.
(author)
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Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease : the omega-3 Alzheimer's disease study
- 2009
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In: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 57:1, s. 11-17
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To study the effects of omega (Omega)-3 fatty acid (FA) supplements on weight and appetite in patients with mild to moderate Alzheimer's disease (AD) in relation to inflammatory biomarkers and apolipoprotein E epsilon4 (APOEepsilon4). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Specialist memory clinics in the Stockholm catchment area. PARTICIPANTS: Two hundred four patients (aged 73+/-9, 52% women) with mild to moderate AD. INTERVENTION: Patients with AD received 1.7 g of docosahexaenoic acid (DHA) and 0.6 g of eicosapentaenoic acid (EPA) (Omega-3/Omega-3 group; n=89, aged 73+/-9, 57% women) or placebo 0.6 g of linoleic acid per day (placebo/Omega-3 group; n=85, aged 73+/-9, 46% women) for 6 months. After 6 months, all patients received DHA and EPA for another 6 months. MEASUREMENTS: Anthropometry, biochemical nutritional and inflammatory markers, and appetite assessed by caregiver. RESULTS: Mean weight and body mass index (kg/m(2)) at baseline were 70.0+/-11.8 kg and 24.3+/-3.0 kg/m(2), respectively. At 6- and 12-month follow-up, weight had increased 0.7+/-2.5 kg (P=.02) and 1.4+/-2.9 kg (P<.001) in the Omega-3/Omega-3 group. In the placebo group, weight was unchanged at 6 months but had increased (P=.01) at 12 months follow-up after Omega-3 supplementation was initiated. Appetite improved in the Omega-3/Omega-3 group over the treatment period (P=.01). In logistic regression analyses, not carrying the APOEepsilon4 allele and high plasma DHA concentrations were independently related to weight gain in the combined group of patients at 6 months follow-up. CONCLUSION: A DHA-enriched Omega-3 FA supplement may positively affect weight and appetite in patients with mild to moderate AD. Not carrying the APOEepsilon4 allele and high DHA were independently associated with weight gain.
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30. |
- Jonasson, Junmei Miao, et al.
(author)
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Risks of nontraumatic lower-extremity amputations in patients with type 1 diabetes - A population-based cohort study in Sweden
- 2008
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 31:8, s. 1536-1540
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Journal article (peer-reviewed)abstract
- OBJECTIVE - The purpose of this study was to estimate the risks of nontraumatic lower-extremity amputations (LEAS) in patients With type 1 diabetes. RESEARCH DESIGN AND METHODS - We identified 31,354 patients with type 1 diabetes (15,001 women and 16,353 men) in the Swedish Inpatient Register between 1975 and 2004. The incidence of nontraumatic LEAs was followed up until 31 December 2004 by cross-linkage in the Inpatient Register and linkage to the Death and Migration registers. Poisson regression modeling was used to compare the risks of nontraumatic LEAs during different calendar periods of follow-up, with adjustment for both sex and attained age at follow-up. Standardized incidence ratios (SIRs) were used to estimate the relative risks (RRs) with the age-, sex-, and calendar period-matched general Swedish population as reference. The cumulative probability of nontraumatic LEAs was calculated by the Kaplan-Meier method. RESULTS - In total, 465 patients with type 1 diabetes undenwent nontraumatic LEAS. The risk was lower during the most recent calendar period (2000-2004) than during the period before 2000 (RR 0.6 [95% CI 0.5-0.8]). However, even in this most recent period, the risk for nontraumatic LEAs among these relatively young patients was 86-fold higher than that in the matched general population (SIR 85.8 [72.9-100.3]). By age 65 years, the cumulative probability of having a nontraumatic LEA was 11.0% for women with type 1 diabetes and 20.7% for men with type 1 diabetes. CONCLUSIONS - Although the risks appeared to have declined in recent years, patients with type 1 diabetes still have a very high risk for nontraumatic LEAs.
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31. |
- Kalani, Majid, et al.
(author)
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Effect of dalteparin on healing of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease: a prospective, randomized, double-blind, placebo-controlled study.
- 2003
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In: Diabetes care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 26:9, s. 2575-80
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Chronic foot ulcers are a common, severe, and expensive complication threatening life and limb in patients with diabetes. The aim of the present study was to investigate the effect of dalteparin on ulcer outcome in patients with diabetes, peripheral arterial occlusive disease, and chronic foot ulcers. RESEARCH DESIGN AND METHODS: A total of 87 patients were investigated in a prospective, randomized, double-blind, placebo-controlled trial. Participants were randomized to treatment with subcutaneous injection of 5000 units dalteparin (Fragmin, Pharmacia Corporation; n = 44) or an equivalent volume of physiological saline (n = 43) once daily until ulcer healing or for a maximum of 6 months. Ulcer outcome was investigated by evaluating the number of patients 1). who healed with intact skin; 2). in whom the study ulcer was improved, unchanged, or impaired; or 3). who were amputated above or below the ankle level, as compared with control subjects. RESULTS: Two patients, one on dalteparin and one on placebo, dropped out of the study. Ulcer outcome was significantly better (P = 0.042, two-sided chi(2) test for trend) in the dalteparin group (n = 43) compared with the placebo group (n = 42). A total of 29 patients healed with intact skin (n = 14) or decreased the ulcer area >or=50% (n = 15) in the dalteparin group compared with 20 (n = 9 and 11, respectively) in the placebo group. Five patients in each group showed impaired ulcer healing, i.e., the ulcer area increased >or=50%. Two patients in the dalteparin group were amputated compared with eight in the placebo group. Time to healing with intact skin was 17 +/- 8 weeks in the dalteparin group compared with 16 +/- 7 weeks in placebo group (NS). CONCLUSIONS: The results of the present study indicate that dalteparin improves the outcome of chronic foot ulcers in diabetic patients with peripheral arterial occlusive disease.
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34. |
- Keindl, Magdalena, et al.
(author)
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Increased Plasma Soluble Interleukin-2 Receptor Alpha Levels in Patients With Long-Term Type 1 Diabetes With Vascular Complications Associated With IL2RA and PTPN2 Gene Polymorphisms
- 2020
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In: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 11
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Journal article (peer-reviewed)abstract
- Type 1 diabetes (T1D) is largely considered an autoimmune disease leading to the destruction of insulin-producing pancreatic beta cells. Further, patients with T1D have 3-4-fold increased risk of developing micro- and macrovascular complications. However, the contribution of immune-related factors contributing to these diabetes complications are poorly understood. Individuals with long-term T1D who do not progress to vascular complications offer a great potential to evaluate end-organ protection. The aim of the present study was to investigate the association of inflammatory protein levels with vascular complications (retinopathy, nephropathy, cardiovascular disease) in individuals with long-term T1D compared to individuals who rapidly progressed to complications. We studied a panel of inflammatory markers in plasma of patients with long-term T1D with (n = 81 and 26) and without (n = 313 and 25) vascular complications from two cross-sectional Scandinavian cohorts (PROLONG and DIALONG) using Luminex technology. A subset of PROLONG individuals (n = 61) was screened for circulating immune cells using multicolor flow cytometry. We found that elevated plasma levels of soluble interleukin-2 receptor alpha (sIL-2R) were positively associated with the complication phenotype. Risk carriers of polymorphisms in the IL2RA and PTPN2 gene region had elevated plasma levels of sIL-2R. In addition, cell surface marker analysis revealed a shift from naive to effector T cells in T1D individuals with vascular complications as compared to those without. In contrast, no difference between the groups was observed either in IL-2R cell surface expression or in regulatory T cell population size. In conclusion, our data indicates that IL2RA and PTPN2 gene variants might increase the risk of developing vascular complications in people with T1D, by affecting sIL-2R plasma levels and potentially lowering T cell responsiveness. Thus, elevated sIL-2R plasma levels may serve as a biomarker in monitoring the risk for developing diabetic complications and thereby improve patient care.
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35. |
- Kärvestedt, Lars, et al.
(author)
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The prevalence of peripheral neuropathy in a population-based study of patients with type 2 diabetes in Sweden
- 2011
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In: Journal of diabetes and its complications. - : Elsevier BV. - 1056-8727 .- 1873-460X. ; 25:2, s. 97-106
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Journal article (peer-reviewed)abstract
- Aims To assess peripheral neuropathy following a standardized foot examination protocol in a representative population-based cohort of subjects with type 2 diabetes. Methods In a geographically defined population, aged 40–70 years with diabetes prevalence of 3.5% according to medical records, we investigated 156 type 2 diabetic subjects, 95% Caucasian, mean age 61.7±7.2 years, duration of diabetes 7.0±5.7 years, and HbA1c 7.3±2.4% (6.4% Mono-S), by questionnaires, clinical examinations, blood sampling, and review of medical records. Foot examination included clinical signs of peripheral neuropathy and tests of sensibility with monofilament, tuning fork, and assessments of the vibration perception thresholds (VPT). Results Peripheral autonomic neuropathy (PAN) as judged by two or more signs of dysfunction was the most common and affected 43%. The prevalence of peripheral sensory neuropathy (PSN) was 15% by monofilament, 24% by tuning fork, and 28% by VPT expressed as ZscoreVPT ≥2.0 S.D. Twenty-nine percent had a VPT ≥25 V. Signs of peripheral motor neuropathy (PMN) affected 15%. Peripheral neuropathy, at least one variable, affected 67%, whereas 25% were affected by more than one variable of neuropathy, i.e., polyneuropathy. Exclusion of other identified causes for neuropathy than diabetes reduced the prevalence of diabetic polyneuropathy to 23%. Concurrent diabetic complications were 29% for retinopathy, 14% for incipient nephropathy, and 8% for overt nephropathy. The prevalence of macrovascular complications was 62% for CVD, 26% for PVD, and 11% for cerebrovascular lesion (CVL). Conclusion Peripheral neuropathy was common in this representative type 2 diabetes population. Clinical signs of PAN were the most frequent followed by diminished perception of vibration and touch.
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36. |
- Larsson, Susanna C, et al.
(author)
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Association of diet with serum insulin-like growth factor I in middle-aged and elderly men
- 2005
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In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 81:5, s. 1163-7
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Journal article (peer-reviewed)abstract
- BACKGROUND: Insulin-like growth factor I (IGF-I) has been implicated in several chronic diseases, including cancer, heart disease, and osteoporosis.OBJECTIVE: Our aim was to assess whether intakes of total energy, alcohol, vitamins, minerals, and foods rich in protein and minerals (including red meat, fish and seafood, poultry, and milk) are associated with serum IGF-I concentrations in middle-aged and elderly men.DESIGN: We measured serum IGF-I concentrations in 226 free-living healthy men aged 42-76 y. The average of fourteen 24-h dietary telephone interviews performed over 1 y was used to estimate long-term dietary intake.RESULTS: We observed statistically significant positive associations between intakes of protein (P for trend = 0.001) and zinc (P for trend = 0.002) and serum IGF-I concentrations after adjusting for age. The difference in mean IGF-I concentrations for the highest compared with the lowest quintile of intake was approximately 17% (162 microg/L compared with 139 microg/L) for protein and approximately 16% (166 microg/L compared with 143 microg/L) for zinc. Consumption of red meat (P for trend = 0.05) and fish and seafood (P for trend = 0.07) was modestly positively associated with IGF-I concentrations. Other dietary factors were not associated with IGF-I concentrations.CONCLUSION: In this population of healthy well-nourished men, greater dietary intakes of protein, zinc, red meat, and fish and seafood were associated with higher IGF-I concentrations.
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37. |
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38. |
- Ljung Faxén, Ulrika, et al.
(author)
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HFpEF and HFrEF Display Different Phenotypes as Assessed by IGF-1 and IGFBP-1
- 2017
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In: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164 .- 1532-8414. ; 23:4, s. 293-303
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Journal article (peer-reviewed)abstract
- BackgroundAnabolic drive is impaired in heart failure with reduced ejection fraction (HFrEF) but insufficiently studied in heart failure with preserved ejection fraction (HFpEF). Insulin-like growth factor 1 (IGF-1) mediates growth hormone effects and IGF binding protein 1 (IGFBP-1) regulates IGF-1 activity. We tested the hypothesis that HFpEF and HFrEF are similar with regard to IGF-1 and IGFBP-1.Methods and ResultsIn patients with HFpEF (n = 79), HFrEF (n = 85), and controls (n = 136), we analyzed serum IGF-1 and IGFBP-1 concentrations, correlations, and associations with outcome. Age-standardized scores of IGF-1 were higher in HFpEF, median arbitrary units (interquartile range); 1.21 (0.57–1.96) vs HFrEF, 0.09 (-1.40–1.62), and controls, 0.22 (-0.47-0.96), P overall <.001. IGFBP-1 was increased in HFpEF, 48 (28–79), and HFrEF, 65 (29–101), vs controls, 27(14–35) µg/L, P overall <.001. These patterns persisted after adjusting for metabolic and HF severity confounders. IGF-1 was associated with outcomes in HFrEF, hazard ratio per natural logarithmic increase in IGF-1 SD score 0.51 (95% confidence interval 0.32–0.82, P = .005), but not significantly in HFpEF. IGFBP-1 was not associated with outcomes in either HFpEF nor HFrEF.ConclusionHFpEF and HFrEF phenotypes were similar with regard to increased IGFBP-1 concentrations but differed regarding IGF-1 levels and prognostic role. HFrEF and HFpEF may display different impairment in anabolic drive.
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39. |
- Ljung Faxen, Ulrika, et al.
(author)
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HFpEF and HFrEF exhibit different phenotypes as assessed by leptin and adiponectin
- 2017
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 228, s. 709-716
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Journal article (peer-reviewed)abstract
- Background: Heart failure with reduced ejection fraction (HFrEF) exhibits a reverse metabolic profile. Whether this profile exists in HF with preserved ejection fraction (HFpEF) is unknown. We tested the hypothesis that HFpEF and HFrEF are similar regarding concentrations of and prognostic impact of leptin and adiponectin.Methods: In patients with HFpEF(n = 79), HFrEF(n = 84), and controls(n = 71), we analyzed serum leptin and adiponectin concentrations, their correlations, and associations with outcome.Results: Leptin levels in HFpEF and HFrEF were increased (p < 0.05) compared to controls; with the highest levels in HFpEF, median (IQR), 23.1 (10.2-51.0), vs. HFrEF 15.0 (6.2-33.2), and vs. controls 10.8 (5.4-18.9) ng/mL. There was no difference between HFpEF and HFrEF p=0.125 (adjusted for gender, BMI and age). Leptin was inversely associated with NT-proBNP (r = -0.364 p = 0.001) and associated with better outcome in HFrEF (HR per ln increase of leptin 0.76, 95% CI 0.58-0.99, p = 0.044) but not in HFpEF.Crude levels of adiponectin were similar in HFpEF: 11.8 (7.9-20.1), HFrEF: 13.7 (7.0-21.1), and controls: 10.5 (7.4-15.1) mu g/L. In men, adjusted similarly as leptin, there was no difference between HFpEF and HFrEF, p = 0.310 but, compared to controls, higher levels in HFpEF (p - 0.044) and HFrEF (p - 0.001). Adiponectin correlated positively with NT-proBNP; r = 0.396 p < 0.001 and higher levels were associated with adverse outcome only in HFrEF (HR per ln increase 2.88 (95% CI 1.02-8.14, p = 0.045).Conclusion: HFpEF and HFrEF share elevated levels of leptin and adiponectin. However, the concept of reverse metabolic profile could not be confirmed in HFpEF, suggesting that HFpEF might have a conventional metabolic profile, rather than a distinct HF syndrome.
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40. |
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41. |
- Ma, Jun, et al.
(author)
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Distribution of neuropeptide Y Leu7Pro polymorphism in patients with type 1 diabetes and diabetic nephropathy among Swedish and American populations.
- 2007
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In: Eur J Endocrinol. - 1479-683X. ; 157:5, s. 641-5
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The distribution of Leu7Pro polymorphism in the neuropeptide Y gene shows a geographical north to south gradient of decreasing frequency, suggesting that it may be a population-specific causal variant. This polymorphism is found to be associated with diabetic nephropathy (DN) and coronary heart disease in Finnish women with type 1 diabetes (T1D). The present study aims to evaluate the susceptibility of this polymorphism to the development of DN in two different populations. DESIGN: One sample set consists of 174 (females 98 and males 76) Swedish T1D patients with DN and 249 (females 132 and males 117) patients without DN. Another sample set includes 597 (females 356 and males 241) American T1D patients without DN and 577 (females 264 and males 313) patients with DN, who were descents of European Caucasians and were from the Genetics of Kidneys in Diabetes (GoKinD) Study. METHODS: Genotyping of Leu7Pro polymorphism was performed by dynamic allele-specific hybridization. RESULTS: The C allele frequencies of Leu7Pro polymorphism in T1D patients between Swedish and American GoKinD populations were significantly different (6.3 vs 4.0%; P=0.006). Particularly, the C allele frequency in Swedish female T1D patients with DN was significantly higher in comparison with T1D patients without DN (10.2 vs 4.2%; P=0.011, OR=2.614, 95% confidence intervals: 1.249-5.467). No significant association of this polymorphism with DN was observed in Swedish male T1D patients and the patients from GoKinD. CONCLUSIONS: The present study provides further evidence that Leu7Pro polymorphism confers the susceptibility to the development of DN in Swedish female T1D patients.
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42. |
- Ma, Jun, et al.
(author)
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Genetic association analysis of the adiponectin polymorphisms in type 1 diabetes with and without diabetic nephropathy.
- 2007
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In: J Diabetes Complications. - : Elsevier BV. - 1056-8727. ; 21:1, s. 28-33
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Adiponectin [adipocyte C1q and collagen domain containing (ACDC)] is the most abundant adipose-specific protein. It is beneficial in that it improves insulin sensitivity and mitigates vascular damage, in addition to the possibility of it having anti-inflammatory properties. Clinical evidences demonstrate that serum adiponectin concentrations are increased in patients with type 1 diabetes (T1D) as well as in patients with microvascular complications. However, the genetic influence of the ACDC gene in T1D and diabetic microvascular complications is still unclear. The present study aims to evaluate the association of the ACDC genetic variation in T1D and diabetic nephropathy (DN). MATERIALS AND METHODS: Ten single nucleotide polymorphisms (SNPs) of the ACDC gene were genotyped in 432 T1D patients (of which, 196 had DN) and 187 nondiabetic control subjects, who were all Swedish Caucasians, by using dynamic allele specific hybridization. RESULTS: Single-marker association analysis demonstrated that SNPs +45G15G(T/G) and +276(G/T) were strongly associated with T1D [P=.002, OR=1.855 (1.266-2.717) and P=.001, OR=1.694 (1.337-2.147)]. Further analysis for haplotypes of these two SNPs indicated that one of the common haplotype (T_G) was strongly associated with T1D [P<.001, OR=1.769 (1.430-2.188)]. However, there was no significant difference in the allele frequencies of these two SNPs between the groups of T1D patients with nephropathy and the patients without nephropathy. CONCLUSIONS: The present study thus suggests that SNPs +45G15G(T/G) and +276(G/T) in the ACDC gene are associated with T1D but not with DN among Swedish Caucasians.
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43. |
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44. |
- Mohanty, Soumitra, et al.
(author)
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Diabetes downregulates the antimicrobial peptide psoriasin and increases E. coli burden in the urinary bladder
- 2022
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Journal article (peer-reviewed)abstract
- Diabetes is known to increase susceptibility to infections, partly due to impaired granulocyte function and changes in the innate immunity. Here, we investigate the effect of diabetes, and high glucose on the expression of the antimicrobial peptide, psoriasin and the putative consequences for E. coli urinary tract infection. Blood, urine, and urine exfoliated cells from patients are studied. The influence of glucose and insulin is examined during hyperglycemic clamps in individuals with prediabetes and in euglycemic hyperinsulinemic clamped patients with type 1 diabetes. Important findings are confirmed in vivo in type 2 diabetic mice and verified in human uroepithelial cell lines. High glucose concentrations induce lower psoriasin levels and impair epithelial barrier function together with altering cell membrane proteins and cytoskeletal elements, resulting in increasing bacterial burden. Estradiol treatment restores the cellular function with increasing psoriasin and bacterial killing in uroepithelial cells, confirming its importance during urinary tract infection in hyperglycemia. In conclusion, our findings present the effects and underlying mechanisms of high glucose compromising innate immunity. Patients with diabetes have an increased susceptibility to infections. Here the authors show that high glucose impairs innate immunity through reduced levels of the antimicrobial peptide psoriasin and impaired epithelial barrier function, resulting in an increased risk of urinary tract infection.
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45. |
- Möller, Louise, et al.
(author)
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A follow-up cohort study on the risk of prediabetes, comparing women with previous preeclamptic or normotensive pregnancies
- 2023
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In: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 13:1
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Journal article (peer-reviewed)abstract
- Studies have shown that preeclampsia is associated insulin resistance and cardiovascular events later in life. However, knowledge is lacking regarding a possible association between PE and abnormal glucose tolerance/prediabetes. Thus, the current study aimed to compare the prevalence of prediabetes in women with previous severe preeclampsia to women with previous normotensive pregnancies. Women with severe preeclampsia (index women, n = 45) admitted to Danderyds University Hospital in 1999-2004 were compared to women with normotensive pregnancies, matched for age, parity, and year of delivery (control women, n = 53). In 2013-2016 BMI, blood pressure, waist circumference, insulin, C-peptide, hsCRP, Cystatin C, HDL, triglycerides, and HbA1c were measured and an OGTT was performed. Index women had a higher BMI (p < 0.001) and blood pressure (p < 0.001) in early pregnancy. At follow-up, prediabetes was more common among index women (p = 0.001), as were hypertension (p = 0.003), heredity for diabetes/cardiovascular disease (p = 0.020), and a larger waist circumference (p = 0.024). Preeclampsia increased the risk of having a fasting plasma glucose >= 5.6 mmol/l (aOR 7.28, 95% CI 2.44-21.76) and of prediabetes 11-16 years after index pregnancy (aOR 4.83, 95% CI 1.80-12.97). In conclusion, preeclampsia increases the risk of prediabetes independent of heredity, hypertension, and waist circumference. These findings may have implications for screening and prevention.
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46. |
- Möllsten, Anna, et al.
(author)
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A functional polymorphism in the manganese superoxide dismutase gene and diabetic nephropathy.
- 2007
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:1, s. 265-269
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Journal article (peer-reviewed)abstract
- Oxidative stress has been suggested to contribute to the development of diabetic nephropathy. Manganese superoxide dismutase (MnSOD) protects the cells from oxidative damage by scavenging free radicals. The demand for antioxidants is increased by smoking, which could disturb the balance between antioxidants and radicals. The present study aimed to determine whether a valine/alanine polymorphism in MnSOD (V16A, rs4880), alone or in combination with smoking, can contribute to development of diabetic nephropathy in 1,510 Finnish and Swedish patients with type 1 diabetes. Overt diabetic nephropathy (n = 619) was defined as having an albumin excretion rate (AER) >200 microg/min or renal replacement therapy; incipient diabetic nephropathy was defined as having an AER of 20-200 microg/min (n = 336). The control subjects had diabetes duration of >or=20 years, without albuminuria (AER <20 microg/min) and without antihypertensive treatment (n = 555). In addition to male sex and elevated A1C, smoking was significantly associated with diabetic nephropathy (overt plus incipient), odds ratio (OR) 2.00 (95% CI 1.60-2.50). When controlling for age at onset, diabetes duration, A1C, smoking, and sex, the Val/Val genotype was associated with an increase in risk of diabetic nephropathy (1.32 [1.00-1.74], P = 0.049). When evaluating the combined effect of genotype and smoking, we used logistic regression with stratification according to smoking status and genotype. The high-risk group (ever smoking plus Val/Val genotype) had 2.52 times increased risk of diabetic nephropathy (95% CI 1.73-3.69) compared with the low-risk group, but no departure from additivity was found. Our results indicate that smoking and homozygosity for the MnSOD Val allele is associated with an increased risk of diabetic nephropathy, which supports the hypothesis that oxidative stress contributes to the development of diabetic nephropathy.
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47. |
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48. |
- Möllsten, Anna, et al.
(author)
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The effect of polymorphisms in the renin-angiotensin-aldosterone system on diabetic nephropathy risk
- 2008
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In: Journal of diabetes and its complications. - : Elsevier BV. - 1056-8727 .- 1873-460X. ; 22:6, s. 377-383
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Journal article (peer-reviewed)abstract
- OBJECTIVES:The risk of diabetic nephropathy (DN) can be increased by elevated intraglomerular pressure and glomerular filtration rate, leading to glomerular damage. This can be controlled by the renin-angiotensin-aldosterone (RAA) system, which has an important function regulating both systemic and intrarenal blood pressure. Smoking increases the risk of DN, but not all diabetic patients who smoke develop DN. There is a possibility that smoking has different effects depending on the different genotypes of the individual. We investigated the association of DN with seven polymorphisms in the RAA system and their possible interaction with smoking.SUBJECTS AND METHODS:In the present case-control study, type 1 diabetic patients with diabetes duration > or =20 years, without albuminuria and without antihypertensive treatment (n=197), were included as controls. An albumin excretion rate (AER) of 20-200 microg/min (n=73) was considered as incipient DN, and an AER >200 microg/min was considered as overt DN (n=48). Smoking habits were obtained from questionnaires.RESULTS:Homozygosity for the A allele, of the angiotensin II type 1 receptor (AGTR1) A1166C polymorphism, was associated with increased risk of overt DN (OR=3.04; 99% CI=1.02-9.06), independently of the other associated variables: age, duration of diabetes, ever smoking, HbA1c, and sex. The effect of the AA genotype was enhanced to a four times risk increase among ever-smoking patients. Two alleles of the microsatellite marker adjacent to the angiotensinogen gene were less common among nephropathy cases than among controls, but this was not significant when controlling for the same variables as above.CONCLUSIONS:The risk of having overt DN was increased in patients homozygous for the A1166 allele, and smoking seemed to enhance the effect of the AGTR1 genotype.
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49. |
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50. |
- Nixon Andréasson, Anna, et al.
(author)
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Associations between leptin and self-rated health in men and women
- 2010
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In: Gender Medicine. - : Elsevier BV. - 1550-8579 .- 1878-7398. ; 7:3, s. 261-9
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Journal article (peer-reviewed)abstract
- BACKGROUND: As an important mediator by which the brain receives information about the body's energy state, leptin may be associated with subjectively perceived health. OBJECTIVE: The main aim of the present study was to investigate concurrent and prospective associations between leptin and self-rated health (SRH), a strong predictor of morbidity and mortality, in a random population sample. An additional aim was to examine whether sick leave was associated with leptin and poor SRH. METHODS: In a prospective, population-based cohort study in Sweden, men and women underwent a medical examination in 1998, at which time blood was drawn and participants were asked to respond to a questionnaire concerning demographics, health behavior, and psychosocial factors. In 2000, the participants responded to a second questionnaire sent by postal mail. Spearman rank correlations were used to investigate the relationships between leptin, SRH, sick leave, and background variables. Partial Spearman coefficients were then calculated to investigate the patterns of association between leptin, SRH, and sick leave independent of age, body mass index (BMI), presence of diagnosis, and testosterone or estradiol. RESULTS: A total of 98 men and 104 women, aged 23 to 76 years, and 91 men and 96 women at follow-up, participated in the study. In men, relatively higher levels of leptin were prospectively associated with relatively worse SRH (rho = 0.20; P = 0.05), but the relationship was not significant in the cross-sectional analysis (rho = 0.18; P = 0.07). This association was not found in women. When controlling for age, BMI, presence of diagnosis, and testosterone, higher levels of leptin were associated with poor SRH in men in cross-sectional analysis (rho = 0.27; P < 0.01) but not prospectively. In women, leptin was not associated with SRH in cross-sectional analysis, but relatively higher levels were prospectively associated with better SRH when adjusted for background factors and estradiol (rho = -0.26; P < 0.05). SRH was independently associated with future sick leave in both men (rho = 0.34; P < 0.01) and women (rho = 0.30; P < 0.05), whereas no association between leptin and future sick leave was found. CONCLUSIONS: Contrasting associations were found between men and women in the relationship between leptin and SRH. Based on the finding that higher leptin levels were associated with better SRH in women than in men, along with corroboration from recent studies, we propose that leptin may serve different psychobiological functions in men than in women.
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