1. |
- Locke, Adam E, et al.
(författare)
-
Genetic studies of body mass index yield new insights for obesity biology.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
|
|
2. |
- Rydén, Lars, et al.
(författare)
-
ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD
- 2013
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:39, s. 3035-3087
-
Tidskriftsartikel (refereegranskat)abstract
- This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.
|
|
3. |
- Shungin, Dmitry, et al.
(författare)
-
New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
-
Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
|
|
4. |
- Fall, Tove, 1979-, et al.
(författare)
-
Non-targeted metabolomics combined with genetic analyses identifies bile acid synthesis and phospholipid metabolism as being associated with incident type 2 diabetes
- 2016
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:10, s. 2114-2124
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesisIdentification of novel biomarkers for type 2 diabetes and their genetic determinants could lead to improved understanding of causal pathways and improve risk prediction.MethodsIn this study, we used data from non-targeted metabolomics performed using liquid chromatography coupled with tandem mass spectrometry in three Swedish cohorts (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1138; Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS], n = 970; TwinGene, n = 1630). Metabolites associated with impaired fasting glucose (IFG) and/or prevalent type 2 diabetes were assessed for associations with incident type 2 diabetes in the three cohorts followed by replication attempts in the Cooperative Health Research in the Region of Augsburg (KORA) S4 cohort (n = 855). Assessment of the association of metabolite-regulating genetic variants with type 2 diabetes was done using data from a meta-analysis of genome-wide association studies.ResultsOut of 5961 investigated metabolic features, 1120 were associated with prevalent type 2 diabetes and IFG and 70 were annotated to metabolites and replicated in the three cohorts. Fifteen metabolites were associated with incident type 2 diabetes in the four cohorts combined (358 events) following adjustment for age, sex, BMI, waist circumference and fasting glucose. Novel findings included associations of higher values of the bile acid deoxycholic acid and monoacylglyceride 18:2 and lower concentrations of cortisol with type 2 diabetes risk. However, adding metabolites to an existing risk score improved model fit only marginally. A genetic variant within the CYP7A1 locus, encoding the rate-limiting enzyme in bile acid synthesis, was found to be associated with lower concentrations of deoxycholic acid, higher concentrations of LDL-cholesterol and lower type 2 diabetes risk. Variants in or near SGPP1, GCKR and FADS1/2 were associated with diabetes-associated phospholipids and type 2 diabetes.Conclusions/interpretationWe found evidence that the metabolism of bile acids and phospholipids shares some common genetic origin with type 2 diabetes.Access to research materialsMetabolomics data have been deposited in the Metabolights database, with accession numbers MTBLS93 (TwinGene), MTBLS124 (ULSAM) and MTBLS90 (PIVUS).
|
|
5. |
- Molnár, Christian, et al.
(författare)
-
Islet Engraftment and Revascularization in Clinical and Experimental Transplantation
- 2013
-
Ingår i: Cell Transplantation. - 0963-6897 .- 1555-3892. ; 22:2, s. 243-251
-
Tidskriftsartikel (refereegranskat)abstract
- Background:Proper revascularization after transplantation is assumed to be crucial forappropriate islet graft function.Methods:We developed a novel non-invasive imagingmethod, based on adenoviral transduction of islets with a hypoxia responsive reporter gene,for continuous in vivo monitoring of hypoxia in islet grafts in a mouse model. In addition,morphological data was obtained from a deceased patient previously subject to intraportaltransplantation.Results:We detected only transient hypoxia in a minority of the animalstransplanted. Importantly, a clear response to hypoxia was observed in vitro after removal ofthe islet-grafts on day twenty-eight after transplantation. Also, the morphological data fromthe deceased patient demonstrated an extensive revascularization of the transplanted islets. Infact, no differences could be seen between native, in pancreas biopsies taken prior to isletisolation, and transplanted islets regarding the number, distribution and shape of the bloodvessels. However, fewer small islets (diameter <39μm) were found in the liver compared to those found in native pancreases. Notably, an absolute majority of the transplanted islets were found remaining within the venous lumen, in direct contact with the vessel wall.Conclusions:In conclusion results presented show less pronounced islet graft hypoxia after subcapsulartransplantation than previously reported using more invasive methods. Also, formation of anextensive intra-islet capillary network, similar to that seen in native islets in the pancreas, wasseen after clinical islet transplantation.
|
|
6. |
- Nowak, Christoph, et al.
(författare)
-
Effect of Insulin Resistance on Monounsaturated Fatty Acid Levels : A Multi-cohort Non-targeted Metabolomics and Mendelian Randomization Study
- 2016
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:10
-
Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or beta-cell responsiveness (disposition index) during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613) followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330), we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining "gold standard" measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development.
|
|
7. |
- Abdelgadir, Moawia, 1965-
(författare)
-
Clinical and Biochemical Features of Adult Diabetes Mellitus in Sudan
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The high prevalence of diabetes mellitus among the Sudanese population is linked to obesity, poor glycaemic control and a high rate of complications. This study investigated 1/ Leptin hormone and its correlations with different biochemical characteristics in Sudanese diabetic subjects, 2/ The impact of glycaemic control on pregnancy outcome in pregnancies with diabetes, 3/ The glycaemic response to Sudanese traditional carbohydrate foods, 4/ The influence of glucose self-monitoring on the glycaemic control among this population, 5/ The health related quality of life in Sudanese subjects with diabetes-related lower limb amputation. Leptin was significantly lower in diabetic subjects compared with controls of same BMI in both females (P =0.0001) and males (P =0.019). In diabetic subjects, serum leptin correlated positively with the homeostatic assessment (HOMA) of both beta-cell function (P =0.018) and insulin resistance (P =.038). In controls, leptin correlated only with insulin resistance. Pregnancy complications were higher among diabetic compared with control women (P<0.0001) and varied with the type of diabetes. Infants of diabetic mothers had a higher incidence of neonatal complications than those of non-diabetic women (P<0.0001). In six Sudanese traditional carbohydrate meals over all differences in incremental AUCs were significant for both plasma glucose (P = 0.0092) and insulin (P = 0.0001). Millet porridge and wheat pancakes displayed significantly lower post-prandial glucose and insulin responses, whereas maize porridge induced a higher post-prandial glucose and insulin response. In type 2 diabetic subjects SMBG or SMUG was not related to glycaemic control. In type 1 diabetic subjects, SMBG was significantly associated with better glycaemic control, as assessed by HbA1c (P=0.02) and blood glucose at clinic visits (P=<0.0001), similar associations were found for SMUG respectively. Neither glycaemic control nor glucose self-monitoring was associated with education level. Diabetic subjects with LLA had significantly poorer HRQL compared to a reference diabetic group (P=<0.0001). Duration of diabetes and amputation had negative impact on HRQL in subjects with LLA (P=<0.0001) respectively. Diabetic subjects with LLA had decreased sense of coherence and high presence of symptoms. Improving health services at the primary level is important to reduce the complications and burden of disease in the Sudanese population.
|
|
8. |
|
|
9. |
|
|
10. |
- Abdelgadir, Moawia, et al.
(författare)
-
Health related quality of life and sense of coherence in Sudanese diabetic subjects with lower limb amputation
- 2009
-
Ingår i: Tohoku journal of experimental medicine. - : Tohoku University Medical Press. - 0040-8727 .- 1349-3329. ; 217:1, s. 45-50
-
Tidskriftsartikel (refereegranskat)abstract
- Quality of life is an important outcome measure in diabetic patients with lower limb amputation (LLA). The aim of this study was to investigate the influence of lower limb amputation on health-related quality of life (HRQOL) in Sudanese diabetic subjects. Additionally the Sense of Coherence scale (SOC-13) and a symptom check list was used in subjects with LLA. A total of 60 (M/F; 40/20) diabetic subjects with LLA and 60 (M/F; 23/37) diabetic reference subjects without LLA, were studied. For both groups HRQOL was measured using The Medical Outcomes Study questionnaire (MOS). Subjects with LLA had significantly poorer HRQOL compared to the reference group in most HRQOL domains (p < 0.0001). Duration of diabetes had the greatest negative impact on HRQOL in both groups, those with LLA (p < 0.0001), and in those without LLA (p < 0.0001), although subjects who were amputated earlier had poorer HRQOL than recently amputated (p < 0.0001). Higher SOC scores were recorded in LLA patients who have greater ratings of positive feelings, family satisfaction and sleep in the HRQOL examination (p < 0.0001). In conclusion, Sudanese diabetic subjects with LLA have a poor quality of life. The triad of diabetes duration, symptoms and amputations, has turned to be important risk factor for poorer HRQOL. Functional and mobility status were suggested to be an important determinant of HRQOL among this population. As the Sudanese population has coherent social relationships, this poor performance of the diabetic subjects will certainly increase the burden on the whole family, in both integrity and economical status. Nevertheless, these deep-rooted social interrelations together with increasing diabetes awareness have substantially improved the family satisfaction among our patients.
|
|
11. |
|
|
12. |
- Abdelgadir, Moawia, et al.
(författare)
-
Low serum adiponectin concentrations are associated with insulin sensitivity independent of obesity in Sudanese subjects with type 2 diabetes mellitus
- 2013
-
Ingår i: Diabetology & Metabolic Syndrome. - : Springer Science and Business Media LLC. - 1758-5996. ; 5, s. 15-
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Prevalence of Type 2 diabetes mellitus among Sudanese population was found to be 3.4% and associated with high rates of complications and obesity. Different adipocytokines are secreted from adipose tissues, among them adiponectin, which was shown to have insulins ensitizing properties and anti-inflammatory, anti-atherogenic effect. The aim of this study was to characterize type 2 diabetes in Sudanese diabetic subjects and controls in respect to hormones influencing or influenced by glucose metabolism. Methods: 104 type 2 diabetic patients (45 men and 59 women), and 75 matched control subjects (34 men and 41 women) were studied. Fasting serum samples were used to measure adiponectin, leptin, insulin, proinsulin, ghrelin and glucose. Body mass index, insulin/proinsulin ratio and (HOMA) insulin resistance and beta cell function were also calculated. Results: Adiponectin serum concentrations were significantly lower in subjects with type 2 diabetes compared with controls subjects (P = 0.002), comparison between males and females did not reach significant levels in both diabetic (P = 0.06) or controls (P = 0.16) groups. In the diabetic group adiponectin correlated positively with serum glucose, negatively with serum proinsulin and HOMA beta cell function (P = 0.03) respectively and serum ghrelin (P = 0.003), but not with BMI, HOMA insulin resistance, insulin or leptin. In controls serum adiponectin correlated negatively with BMI (P = 0.002) but not with other variables. Conclusions: The findings of this study suggest that, adiponectin concentrations independent on BMI as a measure of adiposity, were mostly linked to insulin sensitivity and not to insulin resistance in Sudanese type 2 diabetic subjects, where race specific regulation mechanisms or different type 2 diabetes phenotype suggested being a major contributory factor in clarification the findings of this study.
|
|
13. |
- Abdelgadir, Moawia, et al.
(författare)
-
The influence of glucose self-monitoring on glycaemic control in patients with diabetes mellitus in Sudan
- 2006
-
Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 74:1, s. 90-94
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the influence of self-monitoring of glucose on the glycaemic control in Sudanese diabetic subjects. Subjects and methods: A group of 193 consecutive type 2 and type I diabetic subjects (95 men, 98 women) were studied. In 104 subjects with type 2 diabetes fasting blood glucose was measured using a glucose meter and blood was obtained for serum glucose measurement in the laboratory. In the remaining 89 diabetic subjects random blood glucose was measured using the same glucose meter and a whole blood sample was drawn for laboratory assessment of HbA1c. Data on self-monitoring and other clinical and personal characteristics were recorded. Results: More than 75% of either type I and type 2 diabetic patients never self-monitored blood or urine glucose. In type 2 diabetic subjects self-monitoring of blood or urine glucose was not related to glycaemic control. In type I diabetic subjects, however, self-monitoring of blood glucose was significantly associated with better glycaemic control, as assessed by HbA1c (P = 0.02) and blood glucose at clinic visits (P < 0.0001), and similar associations were found for urine glucose self-monitoring (P = 0.04 and 0.02) respectively. Neither glycaemic control nor glucose self-monitoring was associated with education level. Conclusions: Self-monitoring of blood glucose was not found to be associated to better glycaemic control in Sudanese subjects with type 2 diabetes. In contrast, self-monitoring of both blood and urine glucose was significantly associated with glycaemic control in subjects with type I diabetes. Self-monitoring of urine glucose could be useful where measurement of blood glucose is not available or affordable.
|
|
14. |
- Agardh, Elisabet, et al.
(författare)
-
Ögon
- 2002
-
Ingår i: Diabetes. - 9147048999 ; , s. 236-236
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
15. |
- Ahmad, Shafqat, et al.
(författare)
-
Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome : A Multi-Cohort Nontargeted Metabolomics Observational and Mendelian Randomization Study
- 2022
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 71:2, s. 329-339
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059). We assessed associations between general adiposity measured as body mass index (BMI) and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We employed MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N=7,373), the CHARGE consortium (N=8,631), the Framingham Heart Study (N=2,076) and the DIRECT consortium (N=3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (p-value <0.05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The replication effort provided support for a causal association of adiposity on reduced levels of arachidonic acid (p-value 0.03). Adiposity is associated with variation of large parts of the circulating metabolome, however causality needs further investigation in well-powered cohorts.
|
|
16. |
- Andersson, Per-Erik, et al.
(författare)
-
Regression of left ventricular wall thickness during ACE-inhibitor treatment of essential hypertension is associated with an increase in insulin mediated skeletal muscle blood flow
- 1998
-
Ingår i: Blood Pressure. - 0803-7051 .- 1651-1999. ; 7:2, s. 118-126
-
Tidskriftsartikel (refereegranskat)abstract
- Left ventricular hypertrophy (LVH) has been associated with insulin resistance, a condition with an impaired insulin-mediated vasodilation in skeletal muscle. ACE-inhibitors have been reported to be superior to most other antihypertensive drugs in inducing a regression of LVH. In a double-blind study with parallel groups, 50 patients with essential hypertension were randomized to treatment with either fosinopril (20 mg o.d.) or atenolol (50 mg o.d.) for 12-16 weeks. Left ventricle wall thickness (LVWT, defined as the sum of interventricular septum and posterior wall), diastolic function (represented by the ratio between the E-wave and the A-wave of mitral blood flow) and femoral artery blood flow (FBF) were evaluated using ultrasonic measurements. FBF was measured at normoinsulinemia and after 2 h of euglycemic hyperinsulinemia. Before treatment, the insulin-induced increase in FBF was inversely related to the LVWT (r = -0.52, p < 0.02). The reduction in ambulatory 24-h SBP/DBP was 13/9 mmHg for fosinopril and 15/14 for atenolol, ambulatory DBP being significantly more reduced by atenolol (p = 0.03 for difference in treatment effect). However, only fosinopril treatment resulted in a significant reduction in LVWT (from 20.5 mm to 19.4 mm, p < 0.05). The degree of reduction in LVWT was related to the increase in FBF in the fosinopril group (r = -0.45, p < 0.05). For fosinopril (but not for atenolol), there was a positive relationship between the change in E/A ratio and the change in femoral artery stroke volume (r = 0.80, p < 0.01). Conclusion: Impaired insulin-induced stimulation of leg blood flow was related to an increased LVWT. Furthermore, during fosinopril treatment, regression of LVWT was associated with enhanced skeletal muscle blood flow during hyperinsulinemia. This indicates that impaired peripheral blood flow (and thereby increased afterload) may be a possible mechanism explaining the previously found association between insulin resistance and cardiovascular hypertrophy.
|
|
17. |
- Arne, Mats, 1954-, et al.
(författare)
-
Physical activity and quality of life in subjects with chronic disease : chronic obstructive pulmonary disease compared with rheumatoid arthritis and diabetes mellitus
- 2009
-
Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 27:3, s. 141-147
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Chronic diseases interfere with the life situation of the affected person in different ways. The aim was to compare the burden of disease in three chronic diseases - chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), diabetes mellitus (DM) - and in healthy subjects, with a particular interest in physical activity, quality of life, and psychological health. DESIGN: Cross-sectional, observational study. SETTING AND SUBJECTS: Postal survey questionnaire to a stratified, random population of 68 460 subjects aged 18-84 years in Sweden. The subjects included were 40-84 years old (n = 43 589) and data were analysed for COPD (n = 526), RA (n = 1120), DM (n = 2149) and healthy subjects (n = 6960). RESULT: Some 84% of subjects with COPD, 74% (RA), 72% (DM), and 60% in healthy subjects (p < 0.001, COPD versus RA, DM, and healthy subjects) had a physical activity level considered too low to maintain good health according to guidelines. Quality of life (EuroQol five-dimension questionnaire, EQ-5D) was lower in COPD and RA than in DM. Anxiety/depression was more common in subjects with COPD (53%) than in those with RA (48%) and DM (35%) (p < 0.001, COPD versus RA and DM), whereas mobility problems were more common in RA (55%) than COPD (48%) and DM (36%) (p < 0.001, RA versus COPD and DM). All differences between groups remained significant after adjusting for age, sex, and socioeconomic background factors. CONCLUSION: Subjects with chronic diseases had a low level of physical activity, most evident in subjects with COPD. COPD and RA had a higher negative impact on quality of life than DM. Our results indicate that increased attention regarding physical inactivity in subjects with chronic diseases is needed to minimize the burden of disease.
|
|
18. |
- Auro, K., et al.
(författare)
-
USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study
- 2008
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:3, s. 464-472
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Genetic variants of upstream transcription factor 1 (USF1) have previously been associated with dyslipidaemias in family studies. Our aim was to further address the role of USF1 in metabolic syndrome and cardiovascular traits at the population level in a large Swedish male cohort (n=2,322) with multiple measurements for risk factors during 32 years of follow-up. METHODS: Participants, born in 1920-1924, were examined at 50, 60, 70 and 77 years of age. The follow-up period for cardiovascular events was 1970-2002. We genotyped three haplotype tagging polymorphisms capturing the major allelic variants of USF1. RESULTS: SNP rs2774279 was associated with the metabolic syndrome. The minor allele of rs2774279 was less common among individuals with metabolic syndrome than among healthy controls [p=0.0029 when metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III; p=0.0073 when defined according to the International Diabetes Federation (IDF)]. The minor allele of rs2774279 was also associated with lower BMI, lower fasting glucose values and higher HDL-cholesterol concentrations in longitudinal analyses. With SNP rs2073658, a borderline association with metabolic syndrome was observed (p=0.036, IDF), the minor allele being the risk-increasing allele. The minor allele of rs2073658 also associated with higher total and LDL-cholesterol, apolipoprotein B-100 and lipoprotein(a) concentrations in longitudinal analyses. Importantly, these trends with respect to the allelic variants prevailed throughout the follow-up time of three decades. CONCLUSIONS/INTERPRETATION: Our results suggest that USF1 variants associate with the metabolic syndrome at population level and influence the cardiovascular risk factors throughout adulthood in a consistent, longitudinal manner.
|
|
19. |
|
|
20. |
- Basu, Samar, et al.
(författare)
-
Cytokine-mediated inflammation is independently associated with insulin sensitivity measured by the euglycemic insulin clamp in a community-based cohort of elderly men
- 2011
-
Ingår i: International Journal of Clinical and Experimental Medicine. - : E-Century Publishing. - 1940-5901. ; 4:2, s. 164-168
-
Tidskriftsartikel (refereegranskat)abstract
- Both clinical and experimental studies suggest a close relation between an inflammatory state and insulin resistance. We investigated the association between cytokine-mediated inflammation (high sensitivity C reactive protein [hsCRP] and interleukin [IL] 6) and insulin sensitivity (insulin-mediated glucose disposal rate, assessed by the euglycemic insulin clamp) in a community-based cohort, with subgroup analyses of normal weight individuals without diabetes mellitus and metabolic syndrome (NCEP). hsCRP and IL- 6 were inversely associated with insulin sensitivity (multivariable-adjusted regression coefficient for 1-SD increase of hsCRP -0.12 (-0.21-(-0.03), p=0.01) and of IL-6 - 0.11 (-0.21-(-0.02), p=0.01) in models adjusting for age and components of the metabolic syndrome (systolic and diastolic blood pressure, antihypertensive drugs, HDL-cholesterol, triglycerides, fasting plasma glucose, waist circumference). The multivariable-adjusted association between hsCRP, IL-6 and insulin sensitivity were of a similar magnitude in normal weight individuals without diabetes and without the metabolic syndrome. Our data show that cytokine -mediated subclinical inflammation is independently associated with decreased insulin sensitivity also in apparently metabolically healthy normal weight individuals, indicating that the interplay between inflammatory processes and insulin resistance is present already in the early stages of the development of glucometabolic disease. (IJCEM1012002).
|
|
21. |
- Basu, Samar, et al.
(författare)
-
Type 1 diabetes is associated with increased cyclooxygenase- and cytokine-mediated inflammation
- 2005
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 28:6, s. 1371-1375
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The extent of involvement of cyclooxygenase (COX)-mediated inflammation in type 1 diabetes is unknown, and the association between the COX- and cytokine-mediated inflammatory responses in type 1 diabetes is not fully understood. RESEARCH DESIGN AND METHODS: Plasma high-sensitivity C-reactive protein (CRP), 24-h urinary and plasma 15-keto-dihydro-prostaglandin F(2alpha) (a metabolite of prostaglandin F(2alpha) [PGF(2alpha)] and an indicator of COX-mediated inflammation), serum amyloid protein A (SAA), and interleukin (IL)-6 (indicators of inflammation) were measured in 38 subjects with type 1 diabetes and 41 healthy age- and sex-matched control subjects. RESULTS: The inflammatory indicators (urinary 15-keto-dihydro-PGF(2alpha), P < 0.01; IL-6, P < 0.04) were increased in men with diabetes. CRP and SAA did not show any significant difference between the diabetic and the control subjects. Urinary levels of 15-keto-dihydro-PGF(2alpha) correlated with the degree of glycemic control, HbA(1c) (r = 0.42, P < 0.0005). No correlation was found between the duration of diabetes and the inflammatory biomarkers or metabolic measurements. CONCLUSIONS: These results suggest that an early low-grade inflammatory process reflected by elevated levels of PGF(2alpha) and IL-6 is involved in type 1 diabetes. Thus, both COX- and cytokine-mediated inflammatory pathways are significantly related to type 1 diabetes.
|
|
22. |
- Berglund, Lars, 1955-, et al.
(författare)
-
Early Insulin Response and Insulin Sensitivity are Equally Important as Predictors of Glucose Tolerance after Correction for Measurement Errors
- 2009
-
Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 86:3, s. 219-224
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: We estimated measurement error (ME) corrected effects of insulin sensitivity (M/I), from euglycaemic insulin clamp, and insulin secretion, measured as early insulin response (EIR) from oral glucose tolerance test (OGTT), on fasting plasma glucose, HbA1c and type 2 diabetes longitudinally and cross-sectional. Methods: : In a population-based study (n = 1128 men) 17 men made replicate measurements to estimate ME at age 71 years. Effect of 1 SD decrease of predictors M/I and EIR on longitudinal response variables fasting plasma glucose (FPG) and HbA1c at follow-ups up to 11 years, were estimated using uncorrected and ME-corrected (with the regression calibration method) regression models. Results: : Uncorrected effect on FPG at age 77 years was larger for M/I than for EIR (effect difference 0.10 mmol/l, 95% CI 0.00;0.21), while ME-corrected effects were similar (0.02 mmol/l, 95% CI -0.13;0.15 mmol/l). EIR had greater ME-corrected impact than M/I on HbA1c at age 82 years (-0.11%, -0.28; -0.01%). Conclusions: : Due to higher ME effect of EIR on glycaemia is underestimated as compared with M/I. By correcting for ME valid estimates of relative contributions of insulin secretion and insulin sensitivity on glycaemia are obtained.
|
|
23. |
- Berglund, Lars, et al.
(författare)
-
Seasonal variations of insulin sensitivity from a euglycemic insulin clamp in elderly men
- 2012
-
Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 117:1, s. 35-40
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionSeasonal variations in hemoglobin-A1c have been reported in diabetic patients, but the underlying mechanisms have not been elucidated.AimsTo study if insulin sensitivity, insulin secretion, and fasting plasma glucose showed seasonal variations in a Swedish population-based cohort of elderly men.Methods Altogether 1117 men were investigated with a euglycemic insulin clamp and measurements of fasting plasma glucose and insulin secretion after an oral glucose tolerance test. Values were analyzed in linear regression models with an indicator variable for winter/summer season and outdoor temperature as predictors.Results During winter, insulin sensitivity (M/I, unit = 100 × mg × min-1 × kg-1/(mU × L-1)) was 11.0% lower (4.84 versus 5.44, P = 0.0003), incremental area under the insulin curve was 16.4% higher (1167 versus 1003 mU/L, P = 0.007). Fasting plasma glucose was, however, not statistically significantly different (5.80 versus 5.71 mmol/L, P = 0.28) compared to the summer season. There was an association between outdoor temperature and M/I (0.57 units increase (95% CI 0.29–0.82, P < 0.0001) per 10°C increase of outdoor temperature) independent of winter/summer season. Adjustment for life-style factors, type 2 diabetes, and medication did not alter these results.Read More:http://informahealthcare.com/doi/abs/10.3109/03009734.2011.628422ConclusionsInsulin sensitivity showed seasonal variations with lower values during the winter and higher during the summer season. Inverse compensatory variations of insulin secretion resulted in only minor variations of fasting plasma glucose. Insulin sensitivity was associated with outdoor temperature. These phenomena should be further investigated in diabetic patients.
|
|
24. |
|
|
25. |
|
|
26. |
|
|
27. |
- Berne, Christian
(författare)
-
Diabetes
- 2001
-
Ingår i: Internmedicin. ; , s. 418-465
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
28. |
- Berne, Christian
(författare)
-
Diabetes
- 2001
-
Ingår i: Trafikmedicin. - : Vägverket. ; , s. 74-81
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
29. |
- Berne, Christian
(författare)
-
Intensiv satsning på framtidens diabetesläkemedel
- 2010
-
Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 107:45, s. 2815-2819
-
Tidskriftsartikel (refereegranskat)abstract
- Adverse reactions, particularly hypoglyceamia, and the relatively modest effects of intensive glucose-lowering therapy on cardiovascular disease in recent large-scale trials have emphasized the need for a development of new therapeutic alternatives. The recently approved incretins have shown promising results but require daily injections. Therefore, intense efforts have been made to prolong the action or to find alternative routes of administration. Exenatide LAR and insulin glargine has recently been compared in a large RCT and shown similar effects on glucose control. Still, some concerns regarding risk of pancreatitis and thyroid cancers exist for GLP-1 agonists. Inhibitors of the sodium glucose cotransporter 2 have shown promising results as add-on therapy to metformin in a recent pivotal trial, with mild adverse effects. Genital infections may be a problem. A trial with an IL-1 receptor antagonist shows a new interesting concept with a putative action to preserve beta-cells. Glucokinase activators and 11_HSD1 inhibitors have shown promising results in phase II trials, but the risk of adverse phenomena with these drugs that interact with important metabolic and hormonal pathways have to be further investigated in humans.
|
|
30. |
|
|
31. |
|
|
32. |
|
|
33. |
|
|
34. |
- Biglarnia, Ali-Reza, et al.
(författare)
-
Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation
- 2011
-
Ingår i: Transplant International. - : John Wiley & Sons. - 0934-0874 .- 1432-2277. ; 24:8, s. e61-e66
-
Tidskriftsartikel (refereegranskat)abstract
- We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.
|
|
35. |
- Biglarnia, Ali-Reza, et al.
(författare)
-
Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation
- 2011
-
Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 24:8, s. e61-e66
-
Tidskriftsartikel (refereegranskat)abstract
- We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.
|
|
36. |
- Biglarnia, Ali-Reza, et al.
(författare)
-
Transplantation av pankreas botande alternativ vid typ 1-diabetes : [Transplantation of pancreas, a curative option for type 1 diabetes]
- 2012
-
Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 109:39-40, s. 1754-1757
-
Tidskriftsartikel (refereegranskat)abstract
- In the past decade, pancreas transplantation (PTx) has become increasingly attractive as a curative treatment in patients with labile diabetes and secondary complications. In the United Kingdom, the percentage of deceased-donors utilized for PTx increased 5-fold between 2003 and 2007. The trend towards a higher number of annual pancreas transplantations is also observed in Sweden. The increasing activity and the excellent outcome are consequences of meticulous surgery, effective immunsuppression and adequate follow-up. The present report descibes the current status of PTx and shows the short- and long-term results during the last decade in Sweden.
|
|
37. |
|
|
38. |
- Bjuhr, Mathias, et al.
(författare)
-
External quality assessment of HbA(1c) for point of care testing
- 2006
-
Ingår i: Upsala Journal of Medical Sciences. - 0300-9734 .- 2000-1967. ; 111:2, s. 201-207
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives. To evaluate the long term total imprecision of HbA(1c) testing within the county of Uppsala in relation to the Swedish analytical goal of coefficient of variation (CV) < 3% for HbA(1c) and to study the cost of an external quality assurance program for point-of-care HbA(1c) The county uses Bayer DCA 2000 (TM) for point-of care HbA(1c) testing currently having 23 of these instruments. Methods. Method imprecision was assessed by analysis of patient samples performed as split samples during a 3 year period (2002-2004) as part of the quality assurance program for point-of-care HbA(1c) testing. The samples were first analysed on a Bayer DCA 2000 (TM) and the samples were then sent to the centralised laboratory for reanalysis with an HPLC system (Variant II (TM), Biorad). The testing was performed approximately 8 times per year with each instrument. Results. The median CV between the HPLC method and the point-of-care instruments for each unit was slightly higher than 3%. Conclusion. The DCA 2000 (TM) systems have an acceptable imprecision and agreement with the central laboratory. The test results show acceptable agreements within the county regardless where the patient is tested. The cost of the external quality assurance program is calculated to be approximately SEK 1340 (Euro 150) per instrument.
|
|
39. |
|
|
40. |
|
|
41. |
|
|
42. |
|
|
43. |
- Dahlgren, Andreas, et al.
(författare)
-
Variants of the TCF7L2 gene are associated with beta cell dysfunction and confer an increased risk of type 2 diabetes mellitus in the ULSAM cohort of Swedish elderly men
- 2007
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 50:9, s. 1852-1857
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: In a population-based cohort of elderly men with well-defined phenotypes and biochemical markers related to type 2 diabetes mellitus, we analysed two single nucleotide polymorphisms (SNPs), rs7903146 and rs12255372, in the transcription factor 7-like 2 gene (TCF7L2), which are associated with an increased risk of type 2 diabetes mellitus. Materials and methods: The 1,142 subjects were from the population-based Uppsala Longitudinal Study of Adult Men cohort study (see http://www.pubcare.uu.se/ULSAM/ , last accessed in May 2007). Insulin sensitivity was assessed using a euglycaemic-hyperinsulinaemic clamp; fasting intact and 32-33 split proinsulin, immunoreactive insulin and specific insulin were measured in plasma samples. The SNPs rs7903146 and rs12255372 were genotyped using a fluorescent homogeneous single base extension assay. The SNP genotypes were analysed against diabetes prevalence at age 70 using logistic regression and against quantitative biochemical measures using linear regression analysis. Results: We replicated the association with type 2 diabetes mellitus for both SNPs in this cohort of elderly males. The highest significant odds ratio (2.15, 95% CI 1.20-3.85) was found for SNP rs7903146. The odds ratio for SNP rs12255372 was 1.69 (95% CI 1.20-2.39). Both TCF7L2 SNPs were found to be significantly associated with plasma proinsulin when adjusting for insulin sensitivity, both in the whole cohort and when the diabetic subjects were excluded. Analysis for fasting plasma insulin or insulin sensitivity did not give significant results. Conclusions/interpretation: The association between the risk alleles of the two SNPs studied and levels of proinsulin in plasma, identified when adjusting for insulin sensitivity using euglycaemic-hyperinsulinaemic clamp measurements in this study, is an important novel finding.
|
|
44. |
- Dybjer, Elin, et al.
(författare)
-
Diabetes, kognition och demens
- 2019. - 2
-
Ingår i: Diabetes och Metabola Syndromet. - 9789144133621 ; , s. 115-119
-
Bokkapitel (refereegranskat)
|
|
45. |
- Ekberg, Karin, et al.
(författare)
-
C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy
- 2007
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 30:1, s. 71-76
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - C-peptide replacement in animals results in amelioration of diabetes-induced functional and structural abnormalities in peripheral nerves. The present study was undertaken to examine whether C-peptide administration to patients with type 1 diabetes and peripheral neuropathy improves sensory nerve function. RESEARCH DESIGN AND METHODS - This was an exploratory, double-blinded, randomized, and placebo-controlled study with three study groups that was carried out at five centers in Sweden. C-peptide was given as a replacement dose (1.5 mg/day, divided into four subcutaneous doses) or a dose three times higher (4.5 mg/day) during 6 months. Neurological examination and neurophysiological measurements were performed before and after 6 months of treatment with C-peptide or placebo. RESULTS - The age of the 139 patients who completed the protocol was 44.2 ± 0.6 (mean ± SE) years and their duration of diabetes was 30.6 ± 0.8 years. Clinical neurological impairment (NIA) (score >7 points) of the lower extremities was present in 86% of the patients at baseline. Sensory nerve conduction velocity (SCV) was 2.6 ± 0.08 SD below body height-corrected normal values at baseline and improved similarly within the two C-peptide groups (P < 0.007). The number of patients responding with a SCV peak potential improvement >1.0 m/s was greater in C-peptide-treated patients than in those receiving placebo (P < 0.03). In the least severely affected patients (SCV < 2.5 SD below normal at baseline, n = 70) SCV improved by 1.0 m/s (P < 0.014 vs. placebo). NIA score and vibration perception both improved within the C-peptide-treated groups (P < 0.011 and P < 0.002). A1C levels (7.6 ± 0.1% at baseline) decreased slightly but similarly in C-peptide- and placebo-treated patients during the study. CONCLUSIONS - C-peptide treatment for 6 months improves sensory nerve function in early-stage type 1 diabetic neuropathy.
|
|
46. |
|
|
47. |
|
|
48. |
|
|
49. |
- Engström, Sevek, et al.
(författare)
-
Can costs of screening for hypertension and diabetes in dental care and follow-up in primary health care be predicted?
- 2013
-
Ingår i: Upsala Journal of Medical Sciences. - : Informa Healthcare / Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 118:4, s. 256-262
-
Tidskriftsartikel (refereegranskat)abstract
- Aim. The purpose was to assess the direct costs of screening for high blood pressure and blood glucose in dental care and of follow-up in primary health care and, based on these data, arrive at a prediction function. less thanbrgreater than less thanbrgreater thanStudy population. All subjects coming for routine check-ups at three dental health clinics were invited to have blood pressure or blood glucose measurements; 1,623 agreed to participate. Subjects screening positive were referred to their primary health care centres for follow-up. less thanbrgreater than less thanbrgreater thanMethods. Information on individual screening time was registered during the screening process, and information on accountable time, costs for the screening staff, overhead costs, and analysis costs for the screening was obtained from the participating dental clinics. The corresponding items in primary care, i.e. consultation time, number of follow-up appointments, accountable time, costs for the follow-up staff, overhead costs, and analysis costs during follow-up were obtained from the primary health care centres. less thanbrgreater than less thanbrgreater thanResults. The total screening costs per screened subject ranged from (sic)7.4 to (sic)9.2 depending on subgroups, corresponding to 16.7-42.7 staff minutes. The corresponding follow-up costs were (sic)57-(sic)91. The total resource used for screening and follow-up per diagnosis was 563-3,137 staff minutes. There was a strong relationship between resource use and numbers needed to screen (NNS) to find one diagnosis (P andlt; 0.0001, degree of explanation 99%). less thanbrgreater than less thanbrgreater thanConclusions. Screening and follow-up costs were moderate and appear to be lower for combined screening of blood pressure and blood glucose than for separate screening. There was a strong relationship between resource use and NNS.
|
|
50. |
|
|