| 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. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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