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Low levels of insulin-like growth-factor-binding protein-1 (IGFBP-1) are prospectively associated with the incidence of type 2 diabetes and impaired glucose tolerance (IGT): The Söderåkra Cardiovascular Risk Factor Study
Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden.
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2009 (English)In: Diabetes & Metabolism, ISSN 1262-3636, Vol. 35, no 3, 198-205 p.Article in journal (Refereed) Published
Abstract [en]

AIM: To explore the association between baseline levels of insulin-like growth-factor-binding protein-1 (IGFBP-1), a marker of insulin sensitivity, and the development of type 2 diabetes or impaired glucose tolerance (IGT) in a specifically defined middle-aged population.

METHODS: This cross-sectional population-based screening study was conducted in 1989-1990 and included baseline data for 664 non-diabetic subjects aged 40-59 years. Clinical data were collected and blood samples analyzed for blood glucose, serum lipids and insulin. Blood specimens were frozen at baseline and later analyzed for IGF-I, IGFBP-1 and C-reactive protein (CRP). At the follow-up in 2006, the incidence of type 2 diabetes and IGT was reported based on primary-care medical records.

RESULTS: During the 17-year observation period, 42 subjects (6.3%) developed type 2 diabetes/IGT. Those in the lowest quintile of IGFBP-1 (/=59mug/L), the incidence was 1.5%. Cox's proportional-hazards model regression analyses were used to determine the incidence of type 2 diabetes/IGT, corrected for age and gender, in relation to IGFBP-1, CRP and waist circumference. Subjects in the lowest IGFBP-1 quintile showed an independently increased risk of type 2 diabetes/IGT [hazards ratio (HR): 3.54; 95% CI 1.18-10.6; P=0.024]. For CRP and waist circumference, the corresponding figures were HR: 6.81; 95% CI 2.50-18.6; P<0.001 and HR: 3.33; 95% CI 1.47-7.6; P=0.004, respectively.

CONCLUSION: Low levels of IGFBP-1 predicted the long-term development of type 2 diabetes or IGT in a middle-aged population. The association was independent of CRP and abdominal obesity.

Place, publisher, year, edition, pages
Cedex, France: Elsevier, 2009. Vol. 35, no 3, 198-205 p.
Keyword [en]
CRP, IGFBP-1, Prediction; Screening, Type 2 diabetes, Longitudinal study
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-17690DOI: 10.1016/j.diabet.2008.11.003ISI: 000267655700006PubMedID: 19297224OAI: oai:DiVA.org:liu-17690DiVA: diva2:211316
Available from: 2009-04-14 Created: 2009-04-14 Last updated: 2014-01-13Bibliographically approved
In thesis
1. Screening for Cardiovascular Risk and Diabetes in Primary Health Care: The Söderåkra Risk Factor Screening Study
Open this publication in new window or tab >>Screening for Cardiovascular Risk and Diabetes in Primary Health Care: The Söderåkra Risk Factor Screening Study
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Screening för hjärtkärlrisk och diabetes i primärvården : Söderåkrastudien
Abstract [en]

Background: Cardiovascular disease (CVD) has been the predominant cause of morbidity and mortality for many decades in Sweden. Preventive work in primary health care through individual approach and community-based programmes has shown some success. Still, we need better risk assessment tools and health strategies to lessen the burden of CVD in our population.

Methods: This thesis is based on four studies that explore the cardiovascular risk factor pattern and its development to CVD morbidity and mortality in the middle-aged (40-59 years) population in Söderåkra, southern Sweden, 1989-2006. At a single physician consultation in 1989-1990 the participants provided information about lifestyle in a self-administered questionnaire, underwent a physical examination and received medical advice after a laboratory investigation. The laboratory tests consisted mainly of blood glucose, serum lipids and thyroid function tests. Blood samples were also frozen for later analyses. A telephone interview on self-reported lifestyle changes was conducted ten years later. In 2006, primary health care medical records were studied for incident diabetes and also for impaired glucose tolerance (IGT). Finally, national registers were studied for incident fatal or nonfatal cardiovascular disease until 2006. Cardiovascular risk assessments using three separate risk algorithms were applied on the population.

Results: The participation rate was high with 90% attendance. The conclusion of this cross-sectional baseline analysis was that it is meaningful to check for a secondary cause of hyperlipidemia, hypothyroidism, in women with a cholesterol value above 7.0 mmol/L. After 10 years follow-up women reported significantly more lifestyle changes than men, odds ratio (OR) 1.56 (95% CI: 1.11- 2.18; p= 0.010). Men with a history of smoking or CVD at baseline and women with treated hypertension at baseline made successful lifestyle changes, OR 4.77 (95% CI: 2.18-10.5; p<0.001 and OR 1.84 (95% CI: 1.12-3.02; p= 0.016), respectively, than those without these characteristics. Until 2006, 38 participants had developed diabetes and four subjects IGT out of 664 participants, excluding 10 with diabetes at baseline. A low level of IGFBP-1 at baseline was associated with the development of type 2 diabetes/IGT, hazard ratio (HR) 3.54 (95% CI: 1.18-10.6, p=0.024). This was independent of abdominal obesity or inflammation (CRP). After excluding 16 participants with prevalent CVD at baseline, 71 first fatal or nonfatal CVD events in 689 men and women were registered. Several known risk factors and risk markers were applied on this population.

Those that turned out to be significantly associated with development of incident CVD in univariate Cox´s regression proportional hazard analyses where used in three different risk assessment models: the consultation model, SCORE and the extensive model. A non-laboratory-based risk assessment model, including variables easily obtained during one consultation visit to a general practitioner (GP), predicted cardiovascular events as accurately, HR 2.72; (CI 95% 2.18-3.39, p<0.001), as the established SCORE algorithm, HR 2.73; (CI 95% 2.10-3.55, p<0.001), which requires laboratory testing. Furthermore, adding laboratory measurements covering lipids, inflammation and endothelial dysfunction, did not confer any additional value to the prediction of CVD risk, HR 2.72; (CI 95% 2.19-3.37, p<0.001). The c-statistics for the consultation model (0.794; CI 95% 0.762-0.823) was not significantly different from SCORE (0.767; CI 95% 0.733-0.798, p=0.12) or the extended model (0.806; CI 95% 0.774-0.835, p=0.55).

Conclusions: Our study showed that it is worth searching for hypothyroidism, in women with a cholesterol value above 7 mmol/L. The study identified female gender, previous CVD, hypertension and smoking as predictors of positive lifestyle change during follow-up. A low level of IGFBP-1 predicted future diabetes/IGT in this population as did increased waist and CRP. Finally, data on nonlaboratory risk factors obtained during one GP visit predicted future cardiovascular risk as accurately as SCORE or a laboratory-based risk algorithm.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 70 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1110
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17692 (URN)978-91-7393-673-6 (ISBN)
Public defence
2009-04-29, Aulan, Hälsans Hus (ingång 16), Campus US, Linköpings Universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2009-04-14 Created: 2009-04-14 Last updated: 2009-08-21Bibliographically approved

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Petersson, UllaÖstgren, Carl JohanBrudin, Lars

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