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- Zethelius, Björn, 1962-
(författare)
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Proinsulin and Insulin Sensitivity as Predictors of Type 2 Diabetes Mellitus and Coronary Heart Disease : Clinical Epidemiological Studies with up to 27 Years of Follow-Up
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Defects in insulin secretion and insulin action are the major abnormalities in the development of Type 2 diabetes. Hyperinsulinemia is a risk marker for Type 2 diabetes and according to some, but not in all studies also for coronary heart disease (CHD). Conventional insulin assays measure immunoreactive insulin including proinsulin-like molecules. Proinsulin and insulin measured by specific methods, insulin sensitivity measured by the euglycemic insulin clamp and early insulin response after a glucose challenge give more detailed information and may be better estimates of true risk for Type 2 diabetes and CHD. This study examined relationships between proinsulin, insulin, insulin secretion and insulin sensitivity for the development of Type 2 diabetes and CHD. The investigation of the prognostic significance of proinsulin and insulin for the development of Type 2 diabetes and CHD was performed in prospective studies of 50-year and 70-year-old men in a population-based cohort. The results indicated, that increased proinsulin concentrations, was a marker of increased risk for Type 2 diabetes independent of measurements of insulin secretion and insulin sensitivity whereas insulin was not. Proinsulin was shown to be a predictor for CHD mortality and morbidity, respectively, independent of conventional risk factors, whereas insulin was not. Insulin sensitivity measured by the gold standard euglycemic insulin clamp at age 70 was a predictor of CHD morbidity, independently of established risk factors.In summary, these data provide evidence that an increased concentration of proinsulin and not an elevated plasma insulin level per se, that constitutes the association with Type 2 diabetes and CHD and that insulin resistance per se, is associated with CHD risk.
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| 3. |
- Björklund, Kristina, et al.
(författare)
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Isolated ambulatory hypertension predicts cardiovascular morbidity in elderly men
- 2003
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 107:9, s. 1297-302
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Tidskriftsartikel (refereegranskat)abstract
- Background— Little is known about isolated ambulatory hypertension, a state with elevated ambulatory but normal office blood pressure (BP). This study aimed to investigate the prognostic significance of isolated ambulatory hypertension for cardiovascular morbidity in a population of elderly men.Methods and Results— At baseline, 24-hour ambulatory BP and metabolic and cardiac risk profiles were evaluated in 578 untreated 70-year-old men, participants of a population-based cohort. Subjects with isolated ambulatory hypertension (office BP <140/90 and daytime BP ≥135/85) and sustained hypertension (office BP ≥140/90 and daytime BP ≥135/85) had increased plasma glucose, body mass index, and echocardiographically determined left ventricular relative wall thickness compared with normotensive subjects (office BP <140/90 and daytime BP <135/85). Seventy-two cardiovascular morbid events (2.37 per 100 person-years at risk) occurred over 8.4 years of follow-up. The prognostic value of isolated ambulatory and sustained hypertension was assessed with Cox proportional hazard regression. Multivariate models adjusting for serum cholesterol, smoking, and diabetes demonstrated that both isolated ambulatory hypertension (hazard ratio [HR], 2.77; 95% CI, 1.15 to 6.68) and sustained hypertension (HR, 2.94; 95% CI, 1.49 to 5.82) were independent predictors of cardiovascular morbidity. In a multivariate model with continuous BP variables, ambulatory daytime systolic BP (HR for 1 SD increase, 1.47; 95% CI, 1.09 to 1.97) was associated with an adverse outcome independently of office systolic BP.Conclusions— In the present study, isolated ambulatory hypertension as well as sustained hypertension predicted cardiovascular morbidity. The findings suggest that 24-hour ambulatory BP monitoring may disclose important prognostic information also in subjects characterized as normotensive according to office BP.
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| 7. |
- Dunder, Kristina, et al.
(författare)
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Evaluation of a scoring scheme, including proinsulin and the apolipoprotein B/apolipoprotein A1 ratio, for the risk of acute coronary events in middle-aged men : Uppsala Longitudinal Study of Adult Men (ULSAM)
- 2004
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 148:4, s. 596-601
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In recent years, the importance of circulating levels of proinsulin and apolipoproteins as risk factors for myocardial infarction (MI) has been highlighted. The aims of the current study were to investigate whether introduction of these new markers of coronary risk could improve the performance of a risk prediction score and to compare this new score with traditional scoring schemes, such as the Framingham Study and the Prospective Cardiovascular Munster (PROCAM) Study schemes.METHODS: From 1970 to 1973 all 50-year-old men in Uppsala, Sweden, were invited to participate in a health survey aimed at identifying risk factors for cardiovascular disease (the Uppsala Longitudinal Study of Adult Men [ULSAM] cohort). The current study investigated metabolic characteristics at baseline and the incidence of fatal and nonfatal MI (n = 251) during 28.7 years of follow-up in 1108 men who were free of coronary heart disease at baseline.RESULTS: The risk prediction score was derived from one half of the population sample from the ULSAM cohort and included systolic blood pressure, smoking, family history of MI, serum proinsulin, and the ratio between apolipoprotein B and apolipoprotein A1. The score was highly predictive for future MI (hazard ratio, 1.77 for a 1 SD increase; 95% CI, 1.49 to 2.10, P <.0001) in the other half of the population that was not used for generating the score. The ULSAM score performed slightly better than the Framingham and PROCAM scores (evaluated as areas under the receiver operating curves; Framingham, 61%; PROCAM, 63%; ULSAM, 66%; P =.08).CONCLUSIONS: A risk prediction score for MI including proinsulin and the ratio between apolipoprotein B and apolipoprotein A1 was developed in middle-aged men. This score was highly predictive for future fatal and nonfatal MI and proved to be at least as good as the Framingham and the PROCAM scores, being based on traditional risk factors.
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| 10. |
- Wohlin, Martin, et al.
(författare)
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Impaired insulin sensitivity is an independent predictor of common carotid intima-media thickness in a population sample of elderly men.
- 2003
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Ingår i: Atherosclerosis. - 0021-9150. ; 170:1, s. 181-5
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Tidskriftsartikel (refereegranskat)abstract
- Most previous studies of associations between insulin sensitivity and common carotid artery (CCA) atherosclerosis have been conducted in small samples, have not used direct measurement of insulin sensitivity, and have yielded inconclusive results. We investigated associations of CCA intima-media thickness (IMT) and diameter (CCA-D) measured by B-mode ultrasound and insulin sensitivity measured by the euglycemic hyperinsulinemic clamp test together with risk factors of the insulin resistance syndrome in a community-based sample of 493 elderly men. The clamp glucose disposal rate was an independent predictor of CCA-IMT in multivariate models adjusting for blood pressure, smoking, serum cholesterol, and body mass index (1% decrease in CCA-IMT for a 1 unit increase in glucose disposal rate, P=0.009). Glucose disposal rate was significantly related to CCA-D in univariate (r=-0.11, P=0.02) but not in multivariate models. In conclusion, this study is the first to establish impaired insulin sensitivity, measured by the euglycemic hyperinsulinemic clamp test, as an independent predictor of CCA-IMT in a population-based sample of elderly men.
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