| 41. |
- Prokopenko, Inga, et al.
(författare)
-
A Central Role for GRB10 in Regulation of Islet Function in Man.
- 2014
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father.
|
|
| 42. |
- Prokopenko, Inga, et al.
(författare)
-
Variants in MTNR1B influence fasting glucose levels
- 2009
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 77-81
-
Tidskriftsartikel (refereegranskat)abstract
- To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
|
|
| 43. |
- Pyykkonen, Antti-Jussi, et al.
(författare)
-
Association between depressive symptoms and metabolic syndrome is not explained by antidepressant medication: Results from the PPP-Botnia Study
- 2012
-
Ingår i: Annals of Medicine. - : Informa UK Limited. - 1365-2060 .- 0785-3890. ; 44:3, s. 279-288
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction. To study whether the frequently reported association between depressive symptoms and the metabolic syndrome (MetS) and its individual components are secondary to the use of antidepressant medication and to established diabetes or cardiovascular diseases (CVD). Patients and methods. A population-based, random sample of 4,967 women and men aged 18-75 years. MetS was defined according to the new, harmonized criteria. Glucose tolerance was assessed by oral glucose tolerance test (OGTT). CVD, depressive symptoms, and use of antidepressant medication were self-reported. Results. The odds for having the MetS increased over 10% for each standard deviation increase in depressive symptoms. Users of antidepressant medication had more than 50% increased odds for having the MetS. Depressive symptoms were also associated with higher glucose response during the OGTT, higher serum triglyceride and lower HDL-cholesterol concentrations, and higher waist circumference, while use of antidepressant medication was associated with higher triglycerides, waist circumference, and systolic blood pressure. The associations of depressive symptoms were not secondary to use of antidepressant medication and were not explained by established diabetes or CVD. Discussion. Depressive symptoms, the MetS, and the individual components of MetS are related. These associations are not driven by use of antidepressant medication, established diabetes, or CVD.
|
|
| 44. |
- Pyykkonen, Antti-Jussi, et al.
(författare)
-
Depressive Symptoms, Antidepressant Medication Use, and Insulin Resistance The PPP-Botnia Study
- 2011
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 34:12, s. 2545-2547
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Although insulin resistance (IR) may underlie associations between depressive symptoms and diabetes, previous findings have been contradictory. We examined whether depressive symptoms associate with IR and insulin secretion, and, additionally, whether antidepressant medication use may modulate such associations. RESEARCH DESIGN AND METHODS-A total of 4,419 individuals underwent an oral glucose tolerance test (OGTT). Participants with previously or newly diagnosed diabetes are excluded from this sample. The homeostasis model assessment of IR (HOMA-IR) and corrected insulin response (CIR) were calculated. Depressive symptoms and antidepressant medication use were self-reported. RESULTS-After controlling for confounding factors, depressive symptoms were associated with higher fasting and 30-mM insulin during the OGTT and higher HOMA-IR but not CIR. Antidepressant medication use failed to modify these associations. CONCLUSIONS-Depressive symptoms are associated with IR but not with changes in insulin response when corrected for IR in individuals without previously or newly diagnosed diabetes.
|
|
| 45. |
- Pyykkonen, Antti-Jussi, et al.
(författare)
-
Sleep duration and insulin resistance in individuals without type 2 diabetes: The PPP-Botnia Study
- 2014
-
Ingår i: Annals of Medicine. - : Informa UK Limited. - 1365-2060 .- 0785-3890. ; 46:5, s. 324-329
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction. Both short and long sleep duration may increase risk of type 2 diabetes (diabetes). We studied if short and long sleep durations were associated with insulin resistance (IR) and insulin secretion in individuals without diabetes, and if the associations remained after we excluded individuals who reported more frequent and severe complaints of sleep apnea and insomnia. Participants and methods. An oral glucose tolerance test (OGTT) was performed for 722 adults without diabetes. Indices of IR and insulin secretion were calculated. Sleep duration and complaints of sleep apnea and insomnia were self-reported. Results. In comparison to average sleepers (6 - 9 h/night), short sleepers (< 6 h/night) had higher 120-min insulin and AUC glucose, and long sleepers (>= 9 h/night) had higher fasting and 120-min insulin, 120-min glucose, and HOMA(IR) and lower Insulin Sensitivity Index. After adjusting for confounders and after excluding individuals who reported more frequent and severe complaints of sleep apnea and insomnia, long sleep duration remained significantly associated with IR and insulin secretion. Discussion. Long but not short sleep duration is associated with IR and insulin secretion in individuals without diabetes whether or not accompanied by sleep complaints. Long sleepers may benefit from targeted preventions and interventions that aim at reducing risk of future diabetes.
|
|
| 46. |
- Pyykkonen, Antti-Jussi, et al.
(författare)
-
Stressful Life Events and the Metabolic Syndrome - The Prevalence, Prediction and Prevention of Diabetes (PPP)-Botnia Study
- 2010
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 33:2, s. 378-384
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - Stress may play a role in the pathogenesis of the metabolic syndrome. However, the scant evidence available is not population-based, restricting the external validity of the findings. Our aim was to test associations between stressful life events, their accumulation, and the metabolic syndrome in a large population-based cohort. We also tested associations between stress and the individual components related to the metabolic syndrome. RESEARCH DESIGN AND METHODS - This was a population-based, random sample of 3,407 women and men aged 18-78 years residing in Western Finland. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III and International Diabetes Federation criteria. The severity of 15 stressful life events pertaining to finance, work, social relationships, health, and housing was self-rated. RESULTS - in comparison with subjects not reporting any extremely stressful life events, those reporting work- or finance-related events had an increased odds for having the metabolic syndrome. The risk was further increased according to accumulation of stressful finance-related events and to having at least three stressful life events in any of the life domains assessed. Accumulation Of stressful life events was associated with insulin resistance, obesity, and triglycerides. The associations were not confounded by sex, age, lifestyle, or family history of diabetes. CONCLUSIONS - Life events perceived as stressful, particularly those related to finance and work, may be a signal for poor metabolic health.
|
|
| 47. |
- Pyykkonen, Antti-Jussi, et al.
(författare)
-
Subjective Sleep Complaints Are Associated With Insulin Resistance in Individuals Without Diabetes The PPP-Botnia Study
- 2012
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 35:11, s. 2271-2278
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Sleep disorders and subjective sleep complaints have been associated with increased risk of type 2 diabetes. The evidence with respect to insulin resistance (IR) and insulin secretion in individuals without type 2 diabetes has been scarce and elusive. We examined if subjective sleep complaints and their co-occurrence were associated with IR and insulin secretion in adult women and men without diabetes. RESEARCH DESIGN AND METHODS-Women (n = 442) and men (n = 354) 18-75 years of age without type 2 diabetes underwent an oral glucose tolerance test (OGTT), with insulin and glucose measured at fasting and at 30 and 120 min. Complaints related to sleep apnea, insomnia, and daytime sleepiness were self-rated with the Basic Nordic Sleep Questionnaire. RESULTS-In comparison with individuals with no or minor sleep complaints, those with more frequent complaints of sleep apnea, insomnia, and daytime sleepiness were more insulin resistant, as evidenced by higher fasting insulin concentrations and insulin and glucose responses to OGTT, and more frequently had high homeostasis model assessment of IR and low insulin sensitivity index values. The likelihood of being insulin resistant increased significantly and linearly according to the accumulation of co-occurring sleep complaints. These associations changed only a little when adjusted for mediating and confounding factors and for depressive symptoms. Sleep complaints were not associated with indices of deficiency in insulin secretion. CONCLUSIONS-Subjective sleep complaints were associated with IR. The likelihood of being insulin resistant increased according to accumulation of co-occurring sleep complaints. Sleep complaints were not associated with deficiency in insulin secretion. Diabetes Care 35: 2271-2278, 2012
|
|
| 48. |
- Reiling, Erwin, et al.
(författare)
-
Codon 72 polymorphism (rs1042522) of TP53 is associated with changes in diastolic blood pressure over time
- 2012
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 20:6, s. 696-700
-
Tidskriftsartikel (refereegranskat)abstract
- p53 is involved in stress response, metabolism and cardiovascular functioning. The C-allele of rs1042522 in the gene encoding for p53 is associated with longevity and cancer. In this study, we aimed to investigate the association of rs1042522 with changes in blood pressure, BMI and waist circumference using a longitudinal approach. Rs1042522 was analyzed in two longitudinal studies; the Doetinchem Cohort Study (DCS) and the Botnia Prospective Study (BPS). Changes in quantitative traits over time were investigated according to rs1042522 genotypes. An association between rs1042522 and changes in diastolic blood pressure (DBP) in the DCS over time was observed (P=0.004). Furthermore, a borderline significant association was detected with changes in waist circumference over time (P=0.03). These findings were also observed in the BPS (P=0.02 and P=0.05). The C/C-genotype (Pro/Pro) showed the most moderate time-related increase for the studied endpoints. Furthermore, data from the BPS suggested that the C/C-genotype protects against increases in glucose levels over time at 30 and 60 min during oral glucose tolerance test (P=0.01 and P=0.02). In conclusion, we found an association between the C/C-genotype of rs1042522 and changes in DBP and waist circumference over time. This might contribute to the longevity phenotype observed for the same genotype by others. European Journal of Human Genetics (2012) 20, 696-700; doi:10.1038/ejhg.2011.240; published online 21 December 2011
|
|
| 49. |
- Reinbothe, Thomas, et al.
(författare)
-
The human L-type calcium channel Ca(v)1.3 regulates insulin release and polymorphisms in CACNA1D associate with type 2 diabetes.
- 2013
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 56:2, s. 340-349
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Voltage-gated calcium channels of the L-type have been shown to be essential for rodent pancreatic beta cell function, but data about their presence and regulation in humans are incomplete. We therefore sought to elucidate which L-type channel isoform is functionally important and its association with inherited diabetes-related phenotypes. METHODS: Beta cells of human islets from cadaver donors were enriched using FACS to study the expression of the genes encoding voltage-gated calcium channel (Ca(v))1.2 and Ca(v)1.3 by absolute quantitative PCR in whole human and rat islets, as well as in clonal cells. Single-cell exocytosis was monitored as increases in cell capacitance after treatment with small interfering (si)RNA against CACNA1D (which encodes Ca(v)1.3). Three single nucleotide polymorphisms (SNPs) were genotyped in 8,987 non-diabetic and 2,830 type 2 diabetic individuals from Finland and Sweden and analysed for associations with type 2 diabetes and insulin phenotypes. RESULTS: In FACS-enriched human beta cells, CACNA1D mRNA expression exceeded that of CACNA1C (which encodes Ca(v)1.2) by approximately 60-fold and was decreased in islets from type 2 diabetes patients. The latter coincided with diminished secretion of insulin in vitro. CACNA1D siRNA reduced glucose-stimulated insulin release in INS-1 832/13 cells and exocytosis in human beta cells. Phenotype/genotype associations of three SNPs in the CACNA1D gene revealed an association between the C allele of the SNP rs312480 and reduced mRNA expression, as well as decreased insulin secretion in vivo, whereas both rs312486/G and rs9841978/G were associated with type 2 diabetes. CONCLUSION/INTERPRETATION: We conclude that the L-type calcium channel Ca(v)1.3 is important in human glucose-induced insulin secretion, and common variants in CACNA1D might contribute to type 2 diabetes.
|
|
| 50. |
- Ronnback, Mats, et al.
(författare)
-
Complex Relationship Between Blood Pressure and Mortality in Type 2 Diabetic Patients. A Follow-Up of the Botnia Study.
- 2006
-
Ingår i: Hypertension. - 1524-4563. ; 47:Dec 27, s. 168-173
-
Tidskriftsartikel (refereegranskat)abstract
- The presence of hypertension aggravates the high cardiovascular risk in type 2 diabetic patients. Pulse pressure is a marker of arterial stiffness and constitutes a risk factor for cardiovascular mortality. This study examines the relationship between different blood pressure indices and mortality in a cohort of type 2 diabetic patients. A total of 1294 type 2 diabetic patients with a median age of 69.1 years participated in the Botnia Study from 1990 to 1997. In 2004, after a median follow-up of 9.5 years, data on mortality was collected from the national population registry and hospital records. Systolic and diastolic blood pressure correlated negatively with mortality after adjustment for other risk factors. The association between low systolic and diastolic blood pressure and mortality was pronounced in patients with previous cardiovascular disease. A U-shaped association between pulse pressure and mortality was observed in elderly patients. These observations could be linked to arterial stiffness and heart failure. Low blood pressure in high-risk patients is likely to be a marker of poor health rather than the cause of mortality. The results suggest that the role of blood pressure as a risk marker in elderly type 2 diabetic patients with cardiovascular disease needs to be reevaluated.
|
|
