| 1. |
- Cooray, Gerald, et al.
(författare)
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Effects of intensified metabolic control on CNS function in type 2 diabetes
- 2011
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 36:1, s. 77-86
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Tidskriftsartikel (refereegranskat)abstract
- The mild cognitive decline associated with type 2 diabetes (T2DM) has been suggested to be reversible with improved glycemic control. In order to characterise this cognitive decline and study the effects of improved glycemic control we have studied patients with T2DM (N = 28) and healthy control subjects (N = 21). One group of patients with diabetes (N = 15) were given a 2-month treatment of intensified glycemic control, whereas the other group (N = 13) maintained their regular treatment.Cognitive function in four different domains, auditory event-related potentials (ERPs) and resting EEG power spectrum were studied in the two groups of patients and in healthy control subjects before and after the 2-month trial period.There were significant differences at baseline (p < 0.02) between patients with T2DM and controls. Patients had lower scores in two cognitive domains: verbal fluency (p < 0.01) and visuospatial ability (p < 0.03). T2DM also affected ERP with a decrease in N100 amplitude (p < 0.04) and an increase in P300 latency (p < 0.03). Furthermore, resting EEG activity in the beta band (13–30 Hz) was reduced (p < 0.04). The change between 1st and 2nd investigation was significantly different in the three groups of patients/subjects (p < 0.03). Patients receiving intensified treatment for glycemic control had an improvement of cognitive ability in visuospatial ability (p < 0.02) and semantic memory performance (p < 0.04) together with increased resting EEG activity in the alpha band (8–13 Hz, p < 0.02) and connectivity in the theta (4–8 Hz, p < 0.03) and alpha bands (p < 0.03) over central and lateral regions. Furthermore, there was an increase in the connectivity in the beta band (p < 0.04) over the central regions of the scalp.In conclusion, subjects with T2DM had a similar type of cognitive function impairment and EEG/ERP abnormality as previously demonstrated for subjects with type 1 diabetes (T1DM). Intensified therapy showed cognitive improvement not shown for regular treatment, suggesting that the negative effect of T2DM on cognition is reversible by means of improved glycemic control. Furthermore, there was an improvement in electro-physiological measures, suggesting increased availability of compensatory mechanisms in subjects with intensified treatment.
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| 2. |
- Fadl, Helena, 1965-, et al.
(författare)
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Changing diagnostic criteria for gestational diabetes in Sweden-a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol
- 2019
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Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden () is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches. Methods This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included. Discussion The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.
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| 3. |
- Gutefeldt, Kerstin, 1972-
(författare)
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Upper extremity impairments in type 1 diabetes in comparison to matched controls without diabetes : associations to the IGF-system, metabolic factors, disability and quality of life
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Compared with the general population, people with type 1 diabetes (T1D) more often exhibit pathological alterations in musculoskeletal tissue (impairments). Some of these impairments involve the upper extremities, i.e., the shoulders, hands, and fingers. Although present in diabetes, these complications are underdiagnosed and not actively searched for during routine clinical examinations. Furthermore, much is still unclear about these impairments, specifically regarding their etiology, risk factors, and consequences on daily life activities and quality of life. The growth hormone (GH)/insulinlike growth factor (IGF)-system is known to be affected in diabetes, but whether this is involved in upper extremity impairments (UEIs) is unclear. The aim of this thesis was to describe the prevalence of UEIs in patients with diabetes compared with controls. Furthermore, we aimed to search for risk factors of UEIs, and elucidate the impact of UEIs on daily life activities and health-related quality of life (HRQOL). We used two cohorts; the LedIG cohort (papers I–III), a large population-based study in which all patients with a long duration of T1D (>20 years), aged <67 years, living in the south-east region of Sweden were invited to participate, as well as matched controls without diabetes. This study was based on questionnaires as well as blood samples from the participants. The last paper (IV) included a smaller cohort (n=69) of patients with T1D, who both completed a questionnaire and were the subjects of a clinical examination.Paper I: The UEIs were common in diabetes, with a prevalence of up to 48%. Hand paresthesia was the most common impairment, followed by shoulder pain and stiffness. The prevalence of UEIs was 2–4 times higher in patients than in controls and was associated with more activity limitations. Risk factors were heterogeneous for the different UEIs and included female sex, increasing age, longer duration of diabetes, and poor glycemic control.Paper II: The GH-IGF-axis is important for the growth and function of musculoskeletal tissues. We examined differences in the IGF system between patients with T1D on subcutaneous insulin treatment and controls. We found lower levels of IGF-I and insulinlike growth factor-binding protein (IGFBP)-3 and higher levels of GH and IGFBP-1 in patients with T1D than in controls. The largest difference was found in IGFBP-1, and this probably reflected insulin deficiency. The IGF-I levels were increased with increasing insulin doses. However, even at very high insulin doses (>1 U/kg) the IGF-I Z-score was subnormal, indicating that IGF-I cannot be normalized by subcutaneous insulin treatment. Residual endogenous insulin secretion counteracted these alterations. Furthermore, we investigated possible relationships between UEIs and IGF-I, and found no association.Paper III: The HRQOL was lower in patients with T1D than in controls. Patients with shoulder impairments, hand paresthesia, and hand stiffness, but not finger impairments, had lower HRQOL scores than patients without these impairments. The patients with T1D showed a higher frequency of sick leave than controls, and a common reason for this was musculoskeletal impairments.Paper IV: In addition to the self-reported UEIs, the prevalence of UEIs was also investigated by clinical examination. Clinical UEIs were found in 65% of the participants, with shoulder test (hands against back), prayer sign test, and the Phalen’s and Tinel’s tests being most prevalent. We compared self-reported UEIs to clinical UEIs and found that self-reported impairments were associated with clinical examination. We also found that self-reported shoulder impairments, reduced hand strength, and previous surgery for carpal tunnel syndrome and trigger finger were associated with several other UEIs.In current diabetic care, there is no established routine to capture UEIs, as opposed to other known diabetes complications. We show that UEIs are more common in patients with T1D than in controls, and that they are related to impaired HRQOL and daily life activity limitations. Clinical routines including self-reported UEIs, e.g. shoulder stiffness and reduced hand strength, might be used to identify patients with UEIs in need of clinical investigation, enhanced preventive and therapeutic strategies, as well as rehabilitative interventions.
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| 4. |
- Nygren, J, et al.
(författare)
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Disturbed anabolic hormonal patterns in burned patients : the relation to glucagon
- 1995
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Ingår i: Clinical Endocrinology. - : Wiley-Blackwell Publishing Inc.. - 0300-0664 .- 1365-2265. ; 43:4, s. 491-500
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Complex changes in the anabolic regulators of metabolism occur after major injury. We have studied the time course for IGF-I and IGFBP-1 after burn injury and their relations to circulating levels of other anabolic and catabolic hormones. The hormonal patterns during the onset of sepsis were also investigated. Patients. Eight patients (age 36 (6) years, mean (SEM)) with major burn injury (burn area 42 (6)%) were studied. The first 2 days since the burn were used for rehydration therapy (rehydration period), after which a complete total parenteral nutrition (TPN) period was initiated. Seven of the eight patients developed sepsis, confirmed with positive blood cultures, during the study period. Six of the eight survived. Measurements. The hormonal changes determined inthe morning during the first 7 days after the burn and from day 22 to 24 were investigated. The superimposed effects of sepsis were studied by normalizing all data to the day of positive blood cultures and clinical onset of sepsis. Results. On admission, plasma levels of glucagon, IGFBP-1 and GH were elevated while levels of IGF-I were low. During the first week after the burn, morning levels of glucagon and insulin increased while levels of GH and IGF-I decreased. GH levels were still elevated compared to healthy subjects. Despite the increase in insulin levels, IGFBP-1 remained elevated. Three weeks after the burn injury, IGF-I levels were increased but still markedly below normal, while IGFBP-1 levels remained unchanged. Persistent elevations of insulin levels were combined with reductions in glucagon levels. Admission levels of IGFBP-1 correlated to nitrogen loss (negative nitrogen balance) during the first 24 hours after the burn (r = 0.84, P < 0.05). A correlation between negative nitrogen balance and glucagon levels was found during the early catabolic period in the rehydration period (i.e. days 2-3, r = 0.84, P < 0.01). The relative change in IGFBP-1 levels in the rehydration period correlated to changes in glucagon levels (days 2-3 vs admission, r = 0.65, P < 0.05). The insulin/glucagon molar ratio correlated to the IGF-I/IGFBP-1 ratio during both the rehydration period (days 2-3, r = 0.77, P < 0.05) and the third week after the burn (r = 0.77, P < 0.05). During the most catabolic phase in the first week after the burn (TPN period) there was an inverse relation between IGF-I and IGFBP-1 levels (r = -0.83, P < 0.05). During the less catabolic third week after the burn, an inverse correlation was found between IGF-I and glucagon (r = -0.83, P < 0.05). Sepsis, superimposed upon the burn trauma, was associated with transient elevations in IGFBP-1 and reductions in insulin despite elevated levels of glucose and a further 50% increase in nitrogen losses. Conclusions. The present findings show that marked changes in important anabolic regulating factors occur after major burn injury. Uncoupling of the GH-IGF-I axis, and the attenuation of the inhibitory effects of insulin on IGFBP-1, both contribute to the reduction in IGF-I levels and bioavailability, factors which may play an important role in post injury metabolism. Furthermore, these data suggest that of the catabolic hormones (catecholamines, cortisol and glucagon), primarily glucagon seem to be involved in the modulation of IGF-I and IGFBP-1 levels following burn injury.
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| 5. |
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| 6. |
- Olausson, Hanna, et al.
(författare)
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Maternal food restriction during gestation elevates insulin-like growth factor I and insulin-like growth factor binding protein 1 in adult male rat offspring
- 2006
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Ingår i: Nutrition Research. - : Elsevier BV. - 0271-5317 .- 1879-0739. ; 26:7, s. 350-355
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Tidskriftsartikel (refereegranskat)abstract
- Low birth weight due to maternal malnutrition is associated with increased risk of developing diseases in adulthood, for example, cardiovascular disease. Postnatal oxytocin treatment has previously been shown to have positive effects on blood pressure and corticosterone levels in adult offspring from malnourished dams. The aims of this study were to investigate if maternal food restriction during gestation alters plasma levels of insulin-like growth factor I (IGF-I), IGF binding protein 1 (IGFBP-1), glucose, and insulin in adult male rat offspring, and if postnatal oxytocin treatment has any effect on those changes. Adult offspring from food-restricted mothers had increased levels of IGF-I and IGFBP-1 compared with ad libitum–fed offspring. Postnatal oxytocin treatment had no effect on the IGF system in adulthood. In conclusion, maternal malnutrition during gestation altered the IGF system in adult rat offspring.
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| 7. |
- Sohlström, Annica, 1959-, et al.
(författare)
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Oxytocin treatment during early life influences reproductive performance in ad libitum fed and food-restricted female rats
- 2002
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Ingår i: Biology of the Neonate. - : S. Karger AG. - 0006-3126 .- 1421-9727. ; 81:2, s. 132-138
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Tidskriftsartikel (refereegranskat)abstract
- Oxytocin treatment may permanently alter endocrine axes resulting in anti-stress and anabolic effects. However, the nutritional status influences the effects of oxytocin. The specific aims of this study were to investigate the effects of postnatal oxytocin treatment on reproductive performance in adult life, by studying maternal weight gain, adiposity, plasma levels of IGF-I as well as fetal and placental weights in the following groups of animals: (1) Ad libitum fed dams coming from ad libitum fed mothers. (2) Ad libitum fed dams coming from food-restricted mothers. (3) Food-restricted dams coming from ad libitum fed mothers. (4) Food-restricted dams coming from food-restricted mothers. Oxytocin treatment postnatally had long-term effects and increased adiposity in pregnant dams and stimulated placental and fetal growth relative to saline-treated dams. However, if the dams themselves had been exposed to food restriction during fetal life, the effect of postnatal oxytocin treatment changed. The oxytocin-treated mothers were still fatter but had smaller fetuses. In conclusion, postnatal oxytocin treatment influences reproductive performance in later life but is dependent on the mother’s previous and current nutritional experience.
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| 8. |
- Alehagen, Urban, et al.
(författare)
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Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens
- 2017
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. Methods 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. Findings After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P amp;gt; 0.0001), IGF-1 SD score (F = 29; P amp;lt; 0.0001) and of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme Q10 also on the expression of IGF-1 as one of the mechanistic effects of the intervention. Conclusion Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of intervention with selenium and coenzyme Q10 is needed.
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| 9. |
- Alehagen, Urban, et al.
(författare)
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Selenium and Coenzyme Q10 Supplementation Improves Renal Function in Elderly Deficient in Selenium : Observational Results and Results from a Subgroup Analysis of a Prospective Randomised Double-Blind Placebo-Controlled Trial
- 2020
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- A low selenium intake is found in European countries, and is associated with increased cardiovascular mortality. There is an association between selenium level and the severity of kidney disease. An association between inflammation and selenium intake is also reported. The coenzyme Q10 level is decreased in kidney disease. The aim of this study was to examine a possible association between selenium and renal function in an elderly population low in selenium and coenzyme Q10, and the impact of intervention with selenium and coenzyme Q10 on the renal function. The association between selenium status and creatinine was studied in 589 elderly persons. In 215 of these (mean age 71 years) a randomised double-blind placebo-controlled prospective trial with selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 117) or placebo (n = 98) was conducted. Renal function was determined using measures of glomerular function at the start and after 48 months. The follow-up time was 5.1 years. All individuals were low on selenium (mean 67 μg/L (SD 16.8)). The changes in renal function were evaluated by measurement of creatinine, cystatin-C, and the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) algorithm, and by the use of T-tests, repeated measures of variance and ANCOVA analyses. An association between low selenium status and impaired renal function was observed. Intervention causes a significantly lower serum creatinine, and cystatin-C concentration in the active treatment group compared with those on placebo (p = 0.0002 and p = 0.001 resp.). The evaluation with CKD-EPI based on both creatinine and cystatin-C showed a corresponding significant difference (p < 0.0001). All validations showed corresponding significant differences. In individuals with a deficiency of selenium and coenzyme Q10, low selenium status is related to impaired renal function, and thus supplementation with selenium and coenzyme Q10 results in significantly improved renal function as seen from creatinine and cystatin-C and through the CKD-EPI algorithm. The explanation could be related to positive effects on inflammation and oxidative stress as a result of the supplementation.
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| 10. |
- Andreasson, Anna Nixon, et al.
(författare)
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Leptin and adiponectin : Distribution and associations with cardiovascular risk factors in men and women of the general population
- 2012
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Ingår i: American Journal of Human Biology. - : Wiley. - 1042-0533 .- 1520-6300. ; 24:5, s. 595-601
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In view of the increasing prevalence of obesity worldwide, understanding the role of the recently discovered adipokines leptin and adiponectin is of high clinical relevance. The aim of the present study was to assess the association between levels of leptin and adiponectin with age, known cardiovascular risk factors and to establish whether there are differences between men and women of the general population.METHODS: A total of 98 men and 107 women of the general population, aged between 20 and 74 years, underwent a medical examination at a clinical research center and fasting morning blood samples were also taken.RESULTS: Leptin (mean 7.5 μg l(-1) in men and 16.0 μg l(-1) in women) and adiponectin (mean 7.3 mg l(-1) in men and 11.9 mg l(-1) in women) levels were higher in women than men (Ps < 0.001). Both leptin and adiponectin levels increased with advancing age in both men and women (Ps < 0.05). Leptin was highly associated with factors for metabolic syndrome in men while in women, leptin was highly associated with inflammatory factors. Adiponectin was associated with blood lipids in both men and women, and glucose homeostasis more in women than in men.CONCLUSIONS: Leptin and adiponectin levels were ∼2 times and 1.5 times higher in women than in men, respectively. In addition, although leptin and adiponectin were associated to CVD risk factors in both men and women, we observed differences in specific CVD risk factor groups between men and women. These differences may be due to different regulatory mechanisms and effects of these adipokines in men and women.
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