| 1. |
|
|
| 2. |
- Buschard, Karsten, et al.
(författare)
-
Low serum concentration of sulfatide and presence of sulfated lactosylceramid are associated with Type 2 diabetes. The Skaraborg Project
- 2005
-
Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 22:9, s. 1190-8
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases exocytosis of beta-cell secretory granules, activates K(ATP)-channels and is thereby able to influence insulin secretion through its presence in the islets. A closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is secreted autonomically without the usual first phase response to glucose. The aim was to examine whether serum concentrations of these glycolipids are associated with Type 2 diabetes. METHODS: A case-control study, comprising 286 women and 283 men, was designed using a population-based sample of patients with Type 2 diabetes and a population survey. RESULTS: Low serum concentrations of sulfatide were associated with Type 2 diabetes, independent of traditional risk factors for diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval 1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the highest tertiles. Type 2 diabetes was also associated with detectable amounts of sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women. After adjustment for confounding from other diabetes risk factors, these associations remained basically unchanged. The connections between sulfatide and Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide concentration and positively correlated with sulf-lac-cer (both P < 0.0001, independently). CONCLUSIONS: We report a new, robust and highly significant independent association between Type 2 diabetes and serum concentrations of sulfatide in both sexes, and sulf-lac-cer in females. The associations were also independent of other known diabetes risk factors.
|
|
| 3. |
- Bøg-Hansen, Erik, et al.
(författare)
-
Risk factor clustering in patients with hypertension and non-insulin-dependent diabetes mellitus. The Skaraborg Hypertension Project
- 1998
-
Ingår i: Journal of Internal Medicine. - 1365-2796. ; 243:3, s. 223-232
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To assess the coexistence of hypertension and diabetes, associations with cardiovascular risk factors and the achievement of current treatment goals. DESIGN: A community-based, cross-sectional, observational study. SETTING: Hypertension and diabetes outpatient clinics in primary health care, Skara, Sweden. SUBJECTS: All patients (n = 1116; 488 men, 628 women) who performed an annual follow-up from May 1992 to September 1993. MAIN OUTCOME MEASURES: Hypertension, non-insulin-dependent diabetes mellitus (NIDDM), blood pressure, fasting B-glucose, lipids, HbAlc, body mass index (BMI), waist hip ratio (WHR). RESULTS: Hypertension alone was found in 286 men and 430 women, hypertension and NIDDM combined in 102 men and 102 women, and NIDDM alone in 100 men and 96 women. Taking new cases into account, the proportion of hypertension among NIDDM patients was 57%, and the proportion of NIDDM among hypertensives was 26%. Men and women with both hypertension and NIDDM had a higher systolic blood pressure and women also had a higher diastolic blood pressure (men 168/88 mmHg, women 165/86 mmHg) than those with hypertension alone (men 152/87 mmHg, women 156/82 mmHg) (P < or = 0.001). Cardiovascular risk factors accumulated in patients with both hypertension and NIDDM (triglycerides, BMI and WHR). A diastolic blood pressure < or = 90 mmHg was achieved by 71% men and 84% women with hypertension. HbAlc < 7.5% was attained by 71% men and 70% women with NIDDM. CONCLUSIONS: A considerable coexistence of hypertension and NIDDM was demonstrated. Cardiovascular risk factors clustered in patients with both diseases and their blood pressure was less controlled. These patients thus comprised a clinically defined group at high risk. By current guidelines, control of hypertension and NIDDM seemed appropriate.
|
|
| 4. |
- Henriksson, K M, et al.
(författare)
-
Development of hypertension over 6 years in a birth cohort of young middle-aged men: the Cardiovascular Risk Factor Study in southern Sweden (CRISS).
- 2002
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 252:1, s. 21-26
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To explore the development of hypertension (HT) in a cohort of young middle-aged men. DESIGN: Prospective birth-cohort study of men surveyed over 6 years. SETTING: Helsingborg County Hospital, Sweden, 1990-97. SUBJECTS: A total of 628 men born in 1953-54, all surveyed at 37, 40 and 43 years of age. MAIN OUTCOME MEASURES: Systolic blood pressure (SBP), diastolic blood pressure (DBP), S-cholesterol, body mass index (BMI), alcohol consumption, ethnicity. HT was defined as SBP > or = 140 mmHg and/or DBP > or = 90 mmHg, or ongoing treatment. Using SBP < 130 mmHg and DBP < 85 mmHg as reference, the odds of conversion to HT in men with high normal blood pressure (BP) (SBP 130-139 mmHg and DBP 85-89 mmHg) was investigated. RESULTS: At age 37, 243 men (39%) had reference BP, 167 (26%) had high normal BP and 218 (35%) were hypertensive. Corresponding numbers at age 40 were 265 (42%), 166 (27%) and 197 (31%); and at age 43, 180 (29%), 142 (22%) and 306 (49%), respectively. High normal BP at baseline was associated with the development of HT both at age 40 (odds ratio (OR)=2.45 confidence interval (CI): 1.42-4.22) and at age 43 (OR=2.46, CI: 1.59-3.80), independent of other cardiovascular disease risk factors and ethnicity. The progression to HT was predicted also by S-cholesterol, alcohol consumption, BMI and weight gain. CONCLUSIONS: Over a short-term period, a substantial proportion of young middle-aged men with high normal BP develop HT with overweight and alcohol consumption as important determinants. These findings have implications for the prevention, screening and medical care of HT in this target population.
|
|
| 5. |
- Melander, Olle, et al.
(författare)
-
Association between a variant in the 11 beta-hydroxysteroid dehydrogenase type 2 gene and primary hypertension
- 2000
-
Ingår i: Journal of Human Hypertension. - 1476-5527. ; 14:12, s. 819-823
-
Tidskriftsartikel (refereegranskat)abstract
- The enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11BHSD2) converts cortisol to cortisone in the kidney, thereby protecting the mineralocorticoid receptor from the mineralocorticoid actions of cortisol. The syndrome of Apparent Mineralocorticoid Excess (AME), a rare monogenic form of early onset hypertension with autosomal recessive inheritance, is caused by homozygous or compound heterozygous loss of function mutations in the 11BHSD2 gene. Association has been reported between a microsatellite marker flanking the 11BHSD2 gene (D16S496) and primary hypertension. The aim of this study was to identify variants in the 11BHSD2 gene and to test if such variants or the D16S496 are associated with primary hypertension, in Swedes. To address this, the coding sequences of the 11BHSD2 gene was screened for mutations in 20 patients with primary hypertension with single strand conformation polymorphism and direct DNA sequencing techniques. A polymorphism was identified in exon 3; G534A (Glu178Glu). This polymorphism and the D16S496 microsatellite were tested for association with primary hypertension in a population consisting of 292 patients with primary hypertension and 263 normotensive control subjects. The frequency of G534G homozygotes was higher in patients with primary hypertension than in normotensive control subjects (92.8% vs 87.8%; P < 0.05). The allele frequencies of the D16S496 microsatellite did not differ between the two groups (chi(2) = 11.0, df = 10; P = 0.36). In conclusion, over-representation of individuals homozygous for the G534 allele in hypertensive patients compared with control subjects suggests that a mutation in linkage disequilibrium with the G534A polymorphism could increase susceptibility to primary hypertension. Journal of Human Hypertension (2000) 14, 819-823
|
|
| 6. |
- Melander, Olle, et al.
(författare)
-
Role of the Gly460Trp polymorphism of the alpha-adducin gene in primary hypertension in Scandinavians
- 2000
-
Ingår i: Journal of Human Hypertension. - 1476-5527. ; 14:1, s. 43-46
-
Tidskriftsartikel (refereegranskat)abstract
- Previous studies have suggested that the Trp460 allele of the Gly460Trp polymorphism in the alpha-adducin gene is associated with salt sensitivity and primary hypertension. The present study was undertaken to evaluate if the Trp460 allele of this polymorphism is associated with primary hypertension in Scandinavians. To address this issue, 294 patients with primary hypertension and 265 normotensive control subjects from Sweden were examined and genotyped for the Gly460Trp polymorphism using polymerase chain reaction and restriction fragment length polymorphism methods. We then used a population of 80 patients with primary hypertension and 154 normotensive control subjects from Finland to replicate the findings. The frequency of the Trp460 allele was lower in hypertensive patients than in normotensive controls in the Swedish population (17.7% vs 23.0%; P = 0.03) and in the Finnish population (14.4% vs 19.5%; NS). Therefore we also performed a pooled analysis in which the frequency of the Trp460 allele was significantly lower in hypertensive patients than in normotensive controls (17.0% vs 21. 7%; P = 0.02). In subjects who did not receive antihypertensive medication (n = 447) there was no difference between carriers of the three different codon 460 genotypes (Trp-Trp; Trp-Gly and Gly-Gly) either for systolic (128 +/- 18; 127 +/- 15 and 129 +/- 17 mm Hg, NS) or for diastolic blood pressure (75.6 +/- 12.1; 74.7 +/- 9.3 and 75.0 +/- 10.4 mm Hg, NS). In conclusion, the lower frequency of the Trp460 allele in hypertensive patients than in normotensive controls strongly argues against a pathogenic role of this allele in primary hypertension. The results rather suggest that another variant in linkage disequilibrium with the Gly460Trp polymorphism increases susceptibility for hypertension.Journal of Human Hypertension (2000) 14, 43-46.
|
|
| 7. |
- Roeske-Nielsen, A, et al.
(författare)
-
A variation in the cerebroside sulfotransferase gene is linked to exercise-modified insulin resistance and to type 2 diabetes.
- 2009
-
Ingår i: Experimental diabetes research. - : Hindawi Limited. - 1687-5303 .- 1687-5214. ; 2009
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: The glycosphingolipid beta-galactosylceramide-3-O-sulfate (sulfatide) is present in the secretory granules of the insulin producing beta-cells and may act as a molecular chaperone of insulin. The final step in sulfatide synthesis is performed by cerebroside sulfotransferase (CST) (EC 2.8.2.11). The aim of this study was to investigate whether two single nucleotide polymorphisms (SNP), rs2267161 located in an exon or rs42929 located in an intron, in the gene encoding CST are linked to type 2 diabetes (T2D). METHODS: As a population survey, 265 male and female patients suffering from T2D and 291 gender matched controls were examined. RESULTS: A higher proportion of T2D patients were heterozygous at SNP rs2267161 with both T (methionine) and C (valine) alleles present (49.8% versus 41.3%, P = .04). The calculated odd risk for T2D was 1.47 (1.01-2.15, P = .047). Among female controls, the homozygous CC individuals displayed lower insulin resistance measured by HOMA-IR (P = .05) than the C/T or TT persons; this was particularly prevalent in individuals who exercise (P = .03). CONCLUSION: Heterozygosity at SNP rs2267161 in the gene encoding the CST enzyme confers increased risk of T2D. Females with the CC allele showed lower insulin resistance.
|
|
| 8. |
- Saxena, Richa, et al.
(författare)
-
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
- 2007
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336
-
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.
|
|
