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The Ala isoform of the PPARγ Pro12Ala polymorphism is related to increased abdominal obesity in men but has little impact on cardiovascular risk markers in patients with type 2 diabetes
Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.ORCID iD: 0000-0002-9095-403X
Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
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2009 (English)Article in journal (Other academic) Submitted
Abstract [en]

Background: The interaction of the PPARγ Pro12Ala with obesity and cardiovascular risk is controversial. We aimed to study potential associations of the Ala isoform of this polymorphism with obesity, blood pressure and markers of cardiovascular disease and organ damage in middle aged patients with type 2 diabetes.

Subjects and methods: We recruited 148 women and 246 men in the CArdiovascular Risk factors in Patients with DIabetes – a Prospective study in the Primary health care setting (CARDIPP) study in which early markers of organ damage by cardiac echocardiography, determination of carotid intima media thickness (IMT) and measurement of pulse wave velocity (PWV) was performed. Blood pressures were measured as both as 24-hour ambulatory blood pressure and as a noninvasive recording of central blood pressure. Allelic discrimination was detected with the ABI prism 7500HT Sequence Detection System. Due to the low prevalence of Ala homozygotes, heterozygotes and homozygotes of Ala were defined as Ala isoform in the analyses.

Results: Men with Ala isoform exhibited higher sagittal abdominal diameter (Pro: 25.4±3.4 cm, Ala: 26.7±4.9 cm, p= 0.04) waist circumference (Pro: 104±11 cm, Ala: 108±15 cm, p= 0.046) and body weight (Pro: 91.6±14, Ala: 96.5±18, p= 0.035) than homozygotes for the Pro isoform. However, there were no differences in either gender with respect to blood pressures, left-ventricular mass-index, carotid IMT or carotid-femoral PWV in the participants.

Conclusion: It is unlikely that determination of the PPARγ Pro12Ala isoform in clinic practice adds any major information on cardiovascular risk or circulatory organ damage in patients with type 2 diabetes.

Place, publisher, year, edition, pages
2009.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-18465OAI: oai:DiVA.org:liu-18465DiVA: diva2:219637
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2017-03-27Bibliographically approved
In thesis
1. On the importance of fat cell size, location and signaling in insulin resistance
Open this publication in new window or tab >>On the importance of fat cell size, location and signaling in insulin resistance
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Obesity has reached epidemic proportions worldwide and is associated with insulin resistance, type 2 diabetes and cardiovascular disease. During the past decades, substantial evidence has demonstrated that not only the amount of adipose tissue constitutes a major determinant in the development of metabolic disorders, but also the distribution. The visceral adipose tissue has shown to be stronger correlated with insulin resistance, type 2 diabetes and cardiovascular disease than the subcutaneous depot. When we measured the activity of the nuclear receptor PPARγ in visceral and subcutaneous adipocytes, we found considerably lower activity in fat cells obtained from the visceral portion. This finding provides additional evidence to the unfavorable consequences of visceral obesity. The common PPARγ polymorphism Pro12Ala was studied in type 2 diabetic patients. We found that men with the Ala isoform exhibited higher sagittal abdominal diameter, waist circumference and body weight compared with homozygotes for the Pro isoform. However, no differences in either gender with regard to blood pressure or markers of cardiovascular disease and organ damage could be observed.

In addition to an excessive visceral adipose tissue mass, obese subjects with enlarged adipocytes display an increased risk for developing metabolic disorders compared with individuals exhibiting smaller fat cells but a similar degree of adiposity. The insulin responsiveness in small and large adipocytes obtained from the same subject was examined. Upon insulin stimulation, we found approximately a 2 fold increase of GLUT4 at the plasma membrane in small adipocytes, whereas the large fat cells were refractory to insulin induced GLUT4 translocation. This finding demonstrates a causal relationship between the accumulation of large fat cells in obese subjects and reduced insulin responsiveness.

Caloric restriction in humans ameliorates insulin responsiveness in liver and muscle prior to any substantial weight loss. By combining gene expression profiles of adipose tissue and adipocytes from human subjects undergoing either caloric restriction or overfeeding, we identified genes regulated by changes in caloric intake independent of weight loss per se. We found several genes under the control of mTOR and SREBP1 as well as genes involved in β-oxidation, liberation of fatty acids and glyceroneogenesis to be regulated during the interventions. These genes may indicate pathways and mechanisms mediating the effects of nutrient deprivation and obesity on morbidity and mortality.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 51 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1123
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-18466 (URN)978-91-7393-640-8 (ISBN)
Public defence
2009-06-03, Berzeliussalen, Campus US, Linköpings Universitet, Linköping, 09:00 (English)
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Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2013-09-10Bibliographically approved

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Franck, NiclasLänne, TosteÅstrand, OlovEngvall, JanLindström, TorbjörnÖstgren, Carl JohanNyström, Fredrik H.

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Franck, NiclasLänne, TosteÅstrand, OlovEngvall, JanLindström, TorbjörnÖstgren, Carl JohanNyström, Fredrik H.
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Internal MedicineFaculty of Health SciencesPhysiologyDepartment of Thoracic and Vascular SurgeryClinical PhysiologyDepartment of Endocrinology and Gastroenterology UHLGeneral PracticePrimary Health Care in Motala
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