| 1. |
- Borgquist, Rasmus, et al.
(författare)
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Coronary flow velocity reserve reduction is comparable in patients with erectile dysfunction and in patients with impaired fasting glucose or well-regulated diabetes mellitus
- 2007
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8275. ; 14:2, s. 258-264
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Tidskriftsartikel (refereegranskat)abstract
- Background There is growing evidence that erectile dysfunction is a sentinel for future coronary artery disease. Recently published studies have shown signs of impaired coronary endothelial function in patients with erectile dysfunction, without clinical cardiovascular disease and diabetes. We evaluated the magnitude of coronary vasodilatory dysfunction in men with erectile dysfunction, as compared with men with impaired glucose metabolism (impaired fasting glucose or diabetes) and healthy controls. Methods We investigated men aged 68-73 years with erectile dysfunction (n=12), age-matched men with impaired glucose metabolism, who all proved to have erectile dysfunction (n=15), and age-matched male controls (n=12). Erectile dysfunction was evaluated using the International Index of Erectile Function (IIEF)-5 questionnaire. Coronary flow velocity reserve in the left anterior descending artery was examined using Doppler ultrasound and intravenous adenosine provocation. Results Coronary flow velocities at rest did not differ between the three groups, but maximum coronary flow velocity was significantly lower in the erectile dysfunction group (P= 0.004) and in the impaired glucose metabolism group (P= 0.019), as compared with controls. There was no difference between the erectile dysfunction and impaired glucose metabolism groups. Coronary flow velocity reserve was reduced in the erectile dysfunction group (P=0.026) compared to controls, but was similar compared to the impaired glucose metabolism group. In multivariate analysis including all groups, erectile dysfunction score was the only independent predictor of reduced coronary flow velocity reserve (P=0.020). Conclusions The magnitude of early coronary endothelial and smooth muscle cell dysfunction in otherwise healthy men with erectile dysfunction was comparable to that of patients with impaired glucose metabolism: a well known risk factor for coronary artery disease.
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| 2. |
- Newton-Cheh, Christopher, et al.
(författare)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 3. |
- Ahrén, Bo, et al.
(författare)
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Vildagliptin Enhances Islet Responsiveness to Both Hyper- and Hypoglycemia in Patients with Type 2 Diabetes.
- 2009
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94, s. 1236-1243
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Tidskriftsartikel (refereegranskat)abstract
- Context: Dipeptidyl peptidase-4 (DPP-4) inhibitors act by increasing plasma levels of glucagon-like peptide-1 (GLP-1) and suppressing excessive glucagon secretion in patients with type 2 diabetes (T2DM). However, their effects on the glucagon response to hypoglycemia are not established. Objective: Assess effects of the DPP-4 inhibitor vildagliptin on alpha-cell response to hyper- and hypoglycemia. Design: Single-center, randomized, double-blind, placebo-controlled, two-period crossover study of 28-d treatment, with a 4-wk between-period washout Setting: Participants received study drug as outpatients. Patients: Drug-naïve patients with T2DM and baseline HbA1c
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| 4. |
- Petersson, Ulla, 1947-, et al.
(författare)
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A consultation-based method is equal to SCORE and an extensive laboratory-based method in predicting risk of future cardiovascular disease
- 2009
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - London, UK : Sage Publications. - 1741-8267 .- 1741-8275. ; 16:5, s. 536-540
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: As cardiovascular disease (CVD) is one of the most common causes of mortality worldwide, much interest has been focused on reliable methods to predict cardiovascular risk.DESIGN: A cross-sectional, population-based screening study with 17-year follow-up in Southern Sweden.METHODS: We compared a non-laboratory, consultation-based risk assessment method comprising age, sex, present smoking, prevalent diabetes or hypertension at baseline, blood pressure (systolic >/=140 or diastolic >/=90), waist/height ratio and family history of CVD to Systemic COronary Risk Evaluation (SCORE) and a third model including several laboratory analyses, respectively, in predicting CVD risk. The study included clinical baseline data on 689 participants aged 40-59 years without CVD. Blood samples were analyzed for blood glucose, serum lipids, insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-1, C-reactive protein, asymmetric dimethyl arginine and symmetric dimethyl arginine. During 17 years, the incidence of total CVD (first event) and death was registered.RESULTS: A non-laboratory-based risk assessment model, including variables easily obtained during one consultation visit to a general practitioner, predicted cardiovascular events as accurately [hazard ratio (HR): 2.72; 95% confidence interval (CI): 2.18-3.39, P<0.001] as the established SCORE algorithm (HR: 2.73; 95% CI: 2.10-3.55, P<0.001), which requires laboratory testing. Furthermore, adding a combination of sophisticated laboratory measurements covering lipids, inflammation and endothelial dysfunction, did not confer any additional value to the prediction of CVD risk (HR: 2.72; 95% CI: 2.19-3.37, P<0.001). The c-statistics for the consultation model (0.794; 95% CI: 0.762-0.823) was not significantly different from SCORE (0.767; 95% CI: 0.733-0.798, P=0.12) or the extended model (0.806; 95% CI: 0.774-0.835, P=0.55).CONCLUSION: A risk algorithm based on non-laboratory data from a single primary care consultation predicted long-term cardiovascular risk as accurately as either SCORE or an elaborate laboratory-based method in a defined middle-aged population.
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| 5. |
- Ling, Charlotte, et al.
(författare)
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Genetic and epigenetic factors are associated with expression of respiratory chain component NDUFB6 in human skeletal muscle.
- 2007
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Ingår i: The Journal of clinical investigation. - 0021-9738. ; 117:11, s. 3427-35
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance and type 2 diabetes are associated with decreased expression of genes that regulate oxidative phosphorylation in skeletal muscle. To determine whether this defect might be inherited or acquired, we investigated the association of genetic, epigenetic, and nongenetic factors with expression of NDUFB6, a component of the respiratory chain that is decreased in muscle from diabetic patients. Expression of NDUFB6 was influenced by age, with lower gene expression in muscle of elderly subjects. Heritability of NDUFB6 expression in muscle was estimated to be approximately 60% in twins. A polymorphism in the NDUFB6 promoter region that creates a possible DNA methylation site (rs629566, A/G) was associated with a decline in muscle NDUFB6 expression with age. Although young subjects with the rs629566 G/G genotype exhibited higher muscle NDUFB6 expression, this genotype was associated with reduced expression in elderly subjects. This was subsequently explained by the finding of increased DNA methylation in the promoter of elderly, but not young, subjects carrying the rs629566 G/G genotype. Furthermore, the degree of DNA methylation correlated negatively with muscle NDUFB6 expression, which in turn was associated with insulin sensitivity. Our results demonstrate that genetic, epigenetic, and nongenetic factors associate with NDUFB6 expression in human muscle and suggest that genetic and epigenetic factors may interact to increase age-dependent susceptibility to insulin resistance.
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| 6. |
- Lyssenko, Valeriya, et al.
(författare)
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Clinical risk factors, DNA variants, and the development of type 2 diabetes.
- 2008
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 359:21, s. 2220-2232
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Type 2 diabetes mellitus is thought to develop from an interaction between environmental and genetic factors. We examined whether clinical or genetic factors or both could predict progression to diabetes in two prospective cohorts. METHODS: We genotyped 16 single-nucleotide polymorphisms (SNPs) and examined clinical factors in 16,061 Swedish and 2770 Finnish subjects. Type 2 diabetes developed in 2201 (11.7%) of these subjects during a median follow-up period of 23.5 years. We also studied the effect of genetic variants on changes in insulin secretion and action over time. RESULTS: Strong predictors of diabetes were a family history of the disease, an increased body-mass index, elevated liver-enzyme levels, current smoking status, and reduced measures of insulin secretion and action. Variants in 11 genes (TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX) were significantly associated with the risk of type 2 diabetes independently of clinical risk factors; variants in 8 of these genes were associated with impaired beta-cell function. The addition of specific genetic information to clinical factors slightly improved the prediction of future diabetes, with a slight increase in the area under the receiver-operating-characteristic curve from 0.74 to 0.75; however, the magnitude of the increase was significant (P=1.0x10(-4)). The discriminative power of genetic risk factors improved with an increasing duration of follow-up, whereas that of clinical risk factors decreased. CONCLUSIONS: As compared with clinical risk factors alone, common genetic variants associated with the risk of diabetes had a small effect on the ability to predict the future development of type 2 diabetes. The value of genetic factors increased with an increasing duration of follow-up.
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| 7. |
- Saxena, Richa, et al.
(författare)
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Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336
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Tidskriftsartikel (refereegranskat)abstract
- New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
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| 8. |
- Yasuda, Kazuki, et al.
(författare)
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Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:9, s. 1092-1097
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest P value (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.
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| 9. |
- Appelquist, Malin, et al.
(författare)
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Folkhälsan i östra Skåne 1860–1899 – en studie utifrån provinsialläkarrapporter
- 2005
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Ingår i: Svensk medicinhistorisk tidskrift. - 1402-9871. ; 9:1, s. 95-113
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Tidskriftsartikel (refereegranskat)abstract
- During the last decades of the 19th century Sweden changed from being a developing to a developed country. It was a period when many people emigrated to America and Denmark, due to miserable times. The aim was to investigate the status and development of the public health in the eastern part of the province Skane, Sweden, during the years 1860 to 1899. The investigation included a study of differences in health between city and countryside, men and women, and health problems now and then. The official reports of provincial doctors (general practitioners) from Brosarp (1860-1899) and city doctors from Kristianstad (1883-1899) were studied. The reports included conscription reports, tables of illnesses and deaths, and an annually summarized health report of the district. The district of Brosarp was a very poor area, due to its topographical location. The poverty brought illness, but not as much as could be expected. The infant mortality rate was lower than for the rest of the country. The long distances between the villages impeded the transmission of infectious diseases. The health situation in Kristianstad was also affected by its topographical location. The humid and densely populated city was a hotbed for infections. Sanitary improvements in both Brosarp and Kristianstad resulted in a better health situation at the end of the 19th century. There were several similarities between the studied areas and the developing countries of today, for example regarding malnutrition, traditional medicine and problems with contaminated drinking water. Compared to the health problems of today, poverty and infectious diseases were greater problems during the studied period of time, while problems related to diet and alcohol drinking were similar. More research is needed to relate the public health in Brosarp and Kristianstad to that in other Swedish districts during the same period of time.
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| 10. |
- Berglund, Göran, et al.
(författare)
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Reply to gullberg and ranstam.
- 2009
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 266:6, s. 576-577
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Tidskriftsartikel (refereegranskat)
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