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Risk factors in type 2 diabetes with emphasis on blood pressure, physical activity and serum vitamin D
Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background

Type 2 diabetes is a common chronic disease with a two-fold increased risk for cardiovascular morbidity and mortality and has an increasing prevalence worldwide. This thesis is based on a study conducted in primary health care in Östergötland and Jönköping, Sweden. The aim of the thesis was to evaluate new risk markers to identify patients with high risk of developing cardiovascular disease in middle-aged men and women with type 2 diabetes.

Methods

Data from the cohort study CArdiovascular Risk in type 2 DIabetes – a Prospective study in Primary care (CARDIPP) was used. In paper III data were also used from CARDIPP-Revisited where all participants in the CARDIPP study were invited four years after the baseline investigation for a re-investigation. In paper IV data were used from CAREFUL which is a control group of 185 subjects without diabetes. The investigation included a standard medical history including data on diabetes duration and on-going medication. Anthropometric data were recorded and both office and ambulatory blood pressure were measured. The patients filled out a detailed questionnaire and physical activity was measured by using waist-mounted pedometers. Pedometer-determined physical activity was classified in four groups: Group 1: <5000 steps/day (‘sedentary’); Group 2: 5000-7499 steps/day (‘low active’); Group 3: 7500-9999 steps/day (‘somewhat active’); Group 4: and ≥10 000 steps/day (‘active’). Blood samples were drawn for routine analyses and also frozen for later analyses. The investigations at the departments of physiology included echocardiography, measurements of the carotid intima-media thickness, applanation tonometry and measurements of  sagittal abdominal diameter.

Results

Paper 1:

Patients with a non-dipping systolic blood pressure pattern showed higher left ventricular mass index and pulse wave velocity (PWV) compared with patients with ≥10% decline in nocturnal systolic blood pressure. Patients with <10% decline in nocturnal systolic blood pressure had higher BMI and sagittal abdominal diameter, lower GFR and higher albumin:creatinine ratio and also higher levels of NT-proBNP than patients with a dipping pattern of the nocturnal blood pressure.

Paper 2:

The number of steps/day were inversely significantly associated with BMI, waist circumference and sagittal abdominal diameter, levels of CRP, levels of interleukin-6 and PWV.

Paper 3:

At the 4-year follow-up the change in PWV (ΔPWV) from baseline was calculated. The group with the lowest steps/day had a significantly higher increase in ΔPWV compared with the group with the highest steps/day. The associations between baseline steps/day and ΔPWV remained after further adjustment in a multivariate linear regression statistically significant (p=0.005). 23% of the variation in the study could be explained by our model. Every 1000 extra steps at baseline reduced the change in ΔPWV by 0.103 m/s between baseline and follow-up.

Paper 4:

Low vitamin D levels were associated with significantly increased risk for premature mortality in men with type 2 diabetes. High levels of parathyroid hormone were associated with significantly increased risk for premature mortality in women with type 2 diabetes. These relationships were still statistically significant also when two other well-established risk markers for mortality, PWV and carotid intima-media thickness, were added to the analyses.

Conclusions

Ambulatory blood pressure recording can by addressing the issue of diurnal blood pressure variation, explore early cardiovascular organ damage and microvascular complications that goes beyond effects of standardised office blood pressure measurements. Pedometer-determined physical activity may serve as a surrogate marker for inflammation and subclinical organ damage in patients with type 2 diabetes. There is novel support for the durable vascular protective role of a high level of daily physical activity, which is independent of BMI and systolic blood pressure. The use of pedometers is feasible in clinical practice and provides objective information not only about physical activity but also the future risk for subclinical organ damage in middle-aged people with type 2 diabetes. Our results indicate that low vitamin D levels in men or high parathyroid hormone levels in women give independent prognostic information of an increased risk for total mortality.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. , 55 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1507
National Category
Family Medicine Cardiac and Cardiovascular Systems Endocrinology and Diabetes Geriatrics Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:liu:diva-125911DOI: 10.3384/diss.diva-125911ISBN: 978-91-7685-848-6 (print)OAI: oai:DiVA.org:liu-125911DiVA: diva2:910002
Public defence
2016-04-08, Belladonna, ingång 78, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2016-03-08 Created: 2016-03-08 Last updated: 2017-03-27Bibliographically approved
List of papers
1. Circadian blood pressure variation in patients with type 2 diabetes - relationship to macro- and microvascular subclinical organ damage
Open this publication in new window or tab >>Circadian blood pressure variation in patients with type 2 diabetes - relationship to macro- and microvascular subclinical organ damage
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2011 (English)In: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 5, no 3, 167-173 p.Article in journal (Refereed) Published
Abstract [en]

Aims

To explore the association between nocturnal blood pressure (BP) dipper status and macro- and microvascular organ damage in type 2 diabetes.

Methods

Cross-sectional data from 663 patients with type 2 diabetes, aged 55–66 years, were analysed. Nurses measured office BP and ambulatory BP during 24 h. Individuals with ≥10% difference in nocturnal systolic blood pressure (SBP) relative to daytime values were defined as dippers. Non-dippers were defined as <10% nocturnal decrease in SBP. Estimated glomerular filtration rate (GFR) was calculated and microalbuminuria was measured by albumin:creatinine ratio (ACR). Aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries.

Results

We identified 433 dippers and 230 subjects with a nocturnal non-dipping pattern. Nocturnal SBP dipping was independently of office SBP associated with decreased PWV (p = 0.008), lower ACR (p = 0.001) and NT-proBNP (p = 0.001) and increased GFR (p < 0.001).

Conclusions

We conclude that diurnal BP variation provides further information about early macro- and microvascular subclinical organ damage that goes beyond standardized office BP measurements in patients with type 2 diabetes.

Place, publisher, year, edition, pages
Elsevier, 2011
Keyword
Type 2 diabetes mellitus ambulatory blood pressure arterial stiffness microalbuminuria diurnal blood pressure variation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-75571 (URN)10.1016/j.pcd.2011.04.001 (DOI)000304279600004 ()
Note

funding agencies|Medical Research Council of Southeast Sweden||Center for Medical Image Science and Visualization (CMIV)||Linkoping University||GE Healthcare||Swedish Heart-Lung Foundation||Swedish Research Council| 12661 |

Available from: 2012-03-08 Created: 2012-03-08 Last updated: 2017-12-07Bibliographically approved
2. Pedometer-determined physical activity is linked to low systemic inflammation and low arterial stiffness in Type 2 diabetes
Open this publication in new window or tab >>Pedometer-determined physical activity is linked to low systemic inflammation and low arterial stiffness in Type 2 diabetes
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2012 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, no 9, 1119-1125 p.Article in journal (Refereed) Published
Abstract [en]

Diabet. Med. 29, 11191125 (2012) Abstract Aims The aim of this study was to explore the association between pedometer-determined physical activity versus measures of obesity, inflammatory markers and arterial stiffness in people with Type 2 diabetes. Methods We analysed data from 224 men and 103 women with Type 2 diabetes, aged 5466 years. Physical activity was measured with waist-mounted pedometers during three consecutive days and the number of steps/day were calculated and classified in four groups: andlt; 5000 steps/day, 50007499 steps/day, 75009999 steps/day and andgt;= 10000 steps/day. Blood samples were analysed for lipids, HbA1c, inflammatory markers including C-reactive protein and interleukin-6. Nurses measured blood pressure and anthropometrics. Aortic pulse wave velocity was measured with applanation tonometry over the carotid and femoral arteries. Results Mean steps/day was 7683 +/- 3883 (median 7222, interquartile range 486910 343). There were no differences in age, diabetes duration, blood pressure, lipids or glycaemic control between the four groups of pedometer-determined physical activity. Subjects with higher steps/day had lower BMI (28.8 vs. 31.5 kg/m2, P andlt; 0.001), waist circumference (101.7 vs. 108.0 cm, P andlt; 0.001), lower levels of C-reactive protein (1.6 vs. 2.6 mg/l, P = 0.007), lower levels of interleukin-6 (1.9 vs. 3.8 pg ml, P andlt; 0.001) and lower pulse wave velocity (10.2 vs. 11.0 m/s, P = 0.009) compared with less physically active people. Conclusions We conclude that physical activity measured with pedometer was associated not only with less abdominal obesity, but also with decreased systemic low-grade inflammation as well as with low arterial stiffness, in people with Type 2 diabetes.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2012
Keyword
arterial stiffness, exercise, inflammation, obesity, pedometer, Type 2 diabetes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81816 (URN)10.1111/j.1464-5491.2012.03621.x (DOI)000307470200021 ()
Note

Funding Agencies|Medical Research Council of Southeast Sweden||Center for Medical Image Science and Visualization (CMIV), Linkoping University||GE Healthcare||Swedish Heart-Lung Foundation||Swedish Research Council|12661|

Available from: 2012-09-26 Created: 2012-09-24 Last updated: 2017-12-07Bibliographically approved
3. Pedometer-determined physical activity level and change in arterial stiffness in Type 2 diabetes over 4 years
Open this publication in new window or tab >>Pedometer-determined physical activity level and change in arterial stiffness in Type 2 diabetes over 4 years
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2016 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 33, no 7, 992-997 p.Article in journal (Refereed) Published
Abstract [en]

Aim To explore prospectively the correlation between the level of pedometer-determined physical activity at the start of the study and the change in pulse wave velocity from baseline to 4 years later in people with Type 2 diabetes.

Methods We analysed data from 135 men and 53 women with Type 2 diabetes, aged 54–66 years. Physical activity was measured with waist-mounted pedometers on 3 consecutive days and the numbers of steps/day at baseline were classified into four groups: <5000 steps/day, 5000–7499 steps/day, 7500–9999 steps/day and ≥10 000 steps/day. Pulse wave velocity was measured using applanation tonometry over the carotid and femoral arteries at baseline and after 4 years.

Results The mean (±sd; range) number of steps/day was 8022 (±3765; 956–20 921). The participants with the lowest level of physical activity had a more pronounced increase in the change in pulse wave velocity compared with the participants with the highest. When change in pulse wave velocity was analysed as a continuous variable and adjusted for sex, age, diabetes duration, HbA1c, BMI, systolic blood pressure, pulse wave velocity at baseline, β-blocker use, statin use, unemployment, smoking and diabetes medication, the number of steps/day at baseline was significantly associated with a less steep increase in change in pulse wave velocity (P=0.005). Every 1000 extra steps at baseline corresponded to a lower increase in change in pulse wave velocity of 0.103 m/s.

Conclusions We found that a high level of pedometer-determined physical activity was associated with a slower progression of arterial stiffness over 4 years in middle-aged people with Type 2 diabetes.

Place, publisher, year, edition, pages
John Wiley & Sons, 2016
National Category
Endocrinology and Diabetes Family Medicine Geriatrics Sport and Fitness Sciences Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-125910 (URN)10.1111/dme.12873 (DOI)000379930900018 ()26227869 (PubMedID)
Note

Funding agencies: Medical Research Council of Southeast Sweden; Centre for Medical Image Science and Visualization (CMIV), Linkoping University; GE Healthcare; Swedish Heart-Lung Foundation; Swedish Research Council [12661]; King Gustaf V and Queen Victoria Freemason Found

Available from: 2016-03-08 Created: 2016-03-08 Last updated: 2017-05-03Bibliographically approved
4. A prospective observational study of all-cause mortality in relation to serum 25-OH vitamin D-3 and parathyroid hormone levels in patients with type 2 diabetes
Open this publication in new window or tab >>A prospective observational study of all-cause mortality in relation to serum 25-OH vitamin D-3 and parathyroid hormone levels in patients with type 2 diabetes
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2015 (English)In: Diabetology and Metabolic Syndrome, ISSN 1758-5996, E-ISSN 1758-5996, Vol. 7, no 53Article in journal (Refereed) Published
Abstract [en]

Background: Low levels of vitamin D have been related to increased mortality and morbidity in several non-diabetic studies. We aimed to prospectively study relationships between serum 25-OH vitamin D-3 (vitamin D) and of serum parathyroid hormone (PTH) to total mortality in type 2 diabetes. We also aimed to compare the levels of these potential risk-factors in patients with and without diabetes. Methods: The main study design was prospective and observational. We used baseline data from 472 men and 245 women who participated in the "Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care" study. Patients were 55-66 years old at recruitment, and an age-matched non-diabetic sample of 129 individuals constituted controls for the baseline data. Carotid-femoral pulse-wave velocity (PWV) was measured with applanation-tonometry and carotid intima-media thickness (IMT) with ultrasound. Patients with diabetes were followed for all-cause mortality using the national Swedish Cause of Death Registry. Results: Levels of vitamin D were lower in patients with diabetes than in controls, also after correction for age and obesity, while PTH levels did not differ. Nine women and 24 men died during 6 years of median follow up of the final cohort (n = 698). Vitamin D levels were negatively related to all-cause mortality in men independently of age, PTH, HbA1c, waist circumference, 24-h systolic ambulatory-blood pressure (ABP) and serum-apoB (p = 0.049). This finding was also statistically significant when PWV and IMT were added to the analyses (p = 0.028) and was not affected statistically when medications were also included in the regression-analysis (p = 0.01). In the women with type 2 diabetes, levels of PTH were positively related with all-cause mortality in the corresponding calculations (p = 0.016 without PWV and IMT, p = 0.006 with PWV and IMT, p = 0.045 when also adding medications to the analysis), while levels of vitamin D was without statistical significance (p greater than 0.9). Conclusions: Serum vitamin D in men and serum PTH in women give prognostic information in terms of total-mortality that are independent of regular risk factors in addition to levels of ABP, IMT and PWV.

Place, publisher, year, edition, pages
BioMed Central, 2015
Keyword
Arteriosclerosis; Calcium; Mortality; Parathyroid hormone; Type 2 diabetes; Vitamin D
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-120044 (URN)10.1186/s13098-015-0049-9 (DOI)000356219100001 ()26078787 (PubMedID)
Note

Funding Agencies|Medical Research Council of Southeast Sweden; Futurum; King Gustaf V and Queen Victoria Freemason Foundation; GE Healthcare; Swedish Heart-Lung Foundation; Swedish Research Council [12661]; County Council of Ostergotland; Linkoping University, Department of Medical and Health Sciences

Available from: 2015-07-06 Created: 2015-07-06 Last updated: 2017-12-04

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