Obesity: Nilsson P

Redon J, Cifkova R, Laurent S, Nilsson P, Narkiewicz K, Erdine S, Mancia G, Anonymous00057. · University of Valencia and CIBER 06/03 Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain. · J Hypertens. · Pubmed #18806611 No free full text.

Abstract: The metabolic syndrome considerably increases the risk of cardiovascular and renal events in hypertension. It has been associated with a wide range of classical and new cardiovascular risk factors as well as with early signs of subclinical cardiovascular and renal damage. Obesity and insulin resistance, beside a constellation of independent factors, which include molecules of hepatic, vascular, and immunologic origin with proinflammatory properties, have been implicated in the pathogenesis. The close relationships among the different components of the syndrome and their associated disturbances make it difficult to understand what the underlying causes and consequences are. At each of these key points, insulin resistance and obesity/proinflammatory molecules, interaction of demographics, lifestyle, genetic factors, and environmental fetal programming results in the final phenotype. High prevalence of end-organ damage and poor prognosis has been demonstrated in a large number of cross-sectional and a few number of prospective studies. The objective of treatment is both to reduce the high risk of a cardiovascular or a renal event and to prevent the much greater chance that metabolic syndrome patients have to develop type 2 diabetes or hypertension. Treatment consists in the opposition to the underlying mechanisms of the metabolic syndrome, adopting lifestyle interventions that effectively reduce visceral obesity with or without the use of drugs that oppose the development of insulin resistance or body weight gain. Treatment of the individual components of the syndrome is also necessary. Concerning blood pressure control, it should be based on lifestyle changes, diet, and physical exercise, which allows for weight reduction and improves muscular blood flow. When antihypertensive drugs are necessary, angiotensin-converting enzyme inhibitors, angiotensin II-AT1 receptor blockers, or even calcium channel blockers are preferable over diuretics and classical beta-blockers in monotherapy, if no compelling indications are present for its use. If a combination of drugs is required, low-dose diuretics can be used. A combination of thiazide diuretics and beta-blockers should be avoided.

Redon J, Cifkova R, Laurent S, Nilsson P, Narkiewicz K, Erdine S, Mancia G. · University of Valencia, CIBER 06/03 Fisiopatología de la Obesidad y Nutrición, Institute of Health Carlos III, Madrid, Spain. · J Hypertens. · Pubmed #19262221 No free full text.

Abstract: Arterial hypertension is often part of a constellation of anthropometric and metabolic abnormalities that occur simultaneously to a higher degree than would be expected by chance alone, supporting the existence of a discrete disorder, the so-called metabolic syndrome. It is the result of interactions among a large number of interconnected mechanisms, which eventually lead to both an increase in cardiovascular and renal risk, and the development of diabetes. Mechanisms involved in the metabolic syndrome are obesity, insulin resistance, and a constellation of independent factors, which include molecules of hepatic, vascular, and immunologic origin with pro-inflammatory properties. At each of these key points are interactions of demographics, lifestyle, genetic factors, and environmental fetal programming. Superimposing upon these are infections or chronic exposure or both to certain drugs that can also make their contribution. Skeletal muscle and the liver, not adipose tissue, are the two key insulin-response tissues involved in maintaining glucose balance, although abnormal insulin action in the adipocytes also plays a role in development of the syndrome. Factors commonly associated with and partly dependent on obesity, insulin resistance, such as overactivity of the sympathetic, stimulation of the renin-angiotensin-aldosterone systems, abnormal renal sodium handling, endothelial dysfunction, and large vessels' alterations, may play a key role in the blood pressure elevation of the syndrome.

Sjögren M, Lyssenko V, Jonsson A, Berglund G, Nilsson P, Groop L, Orho-Melander M. · Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, CRC house 91, Malmö, Sweden. · Diabetologia. · Pubmed #18853134 No free full text.

Abstract: AIMS/HYPOTHESIS: The metabolic syndrome is a cluster of factors contributing to increased risk of cardiovascular disease and type 2 diabetes but unifying mechanisms have not been identified. Our aim was to study whether common variations in 17 genes previously associated with type 2 diabetes or components of the metabolic syndrome and variants in nine genes with inconsistent association with at least two components of the metabolic syndrome would also predict future development of components of the metabolic syndrome, individually or in combination. METHODS: Genetic variants were studied in a large prospective study of 16,143 non-diabetic individuals (mean follow-up time 23 years) from the Malmö Preventive Project. In this study, development of at least three of obesity (BMI >or= 30 kg/m(2)), dyslipidaemia (triacylglycerol >or= 1.7 mmol/l and/or lipid-lowering treatment), hypertension (blood pressure >or= 140/90 mmHg and/or antihypertensive medication) and hyperglycaemia (fasting plasma glucose >or= 5.6 mmol/l and/or known diabetes) was defined as development of the metabolic syndrome. The risk of developing at least three components of the metabolic syndrome or the individual components was calculated by logistic regression adjusted for age at baseline, follow-up time and sex. RESULTS: Polymorphisms in TCF7L2 (rs7903146, OR 1.10, 95% CI 1.04-1.17, p = 0.00097), FTO (rs9939609, OR 1.08, 95% CI 1.02-1.14, p = 0.0065), WFS1 (rs10010131, OR 1.07, 95% CI 1.02-1.13, p = 0.0078) and IGF2BP2 (rs4402960, OR 1.07, 95% CI 1.01-1.13, p = 0.021) predicted the development of at least three components of the metabolic syndrome in both univariate and multivariate analysis; in the case of TCF7L2, WFS1 and IGF2BP this was due to their association with hyperglycaemia (p < 0.00001, p = 0.0033 and p = 0.027, respectively) and for FTO it was due to its association with obesity (p = 0.004). A polymorphism in the GCKR gene predicted dyslipidaemia (rs1260326, OR 1.15, 95% CI 1.09-1.22, p < 0.00001) but not the metabolic syndrome. None of the studied polymorphisms was associated with more than two components of the metabolic syndrome. A composite genotype score of the 17 polymorphisms associated with type 2 diabetes predicted the development of at least three components of the metabolic syndrome (OR 1.04, p < 0.00001) and the development of hyperglycaemia (OR 1.06, p < 0.00001). Carriers of >or=19 risk alleles had 51 and 72% increased risk of developing at least three components of the metabolic syndrome and hyperglycaemia, respectively, compared with carriers of <or=12 risk alleles (p < 0.00001 for both). CONCLUSIONS/INTERPRETATION: Polymorphisms in susceptibility genes for type 2 diabetes (TCF7L2, WFS1, IGF2BP2) and obesity (FTO) predispose to the metabolic syndrome by increasing the risk of one specific component of the metabolic syndrome. The findings argue against a unifying genetic component for the metabolic syndrome.

Nordfjäll K, Eliasson M, Stegmayr B, Melander O, Nilsson P, Roos G. · Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. · Obesity (Silver Spring). · Pubmed #18820651 No free full text.

Abstract: Cardiovascular disease (CVD) and obesity have been coupled to short telomere length in peripheral blood. The biological background to this observation is not obvious from the literature. In this study we have analyzed a large set of known risk factors for CVD in relation to telomere length in blood cells on a merged cohort of 989 individuals recruited in the Malmö Diet and Cancer Cohort (MDCC) and the Northern Sweden MONICA project. We found a significant or borderline association between obesity parameters and telomere length in women after age and center adjustments (BMI: r = -0.106, P = 0.021, weight: r = -0.087, P = 0.060, waist circumference: r = -0.099, P = 0.032, hip circumference: r = -0.128, P = 0.005). In men, a positive borderline correlation to high-density lipoprotein (HDL) (r = 0.111, P = 0.053) and a negative correlation to 2-h post-oral glucose-tolerance test (OGTT) was observed (r = -0.202, P = 0.045). In neither group any association was found between telomere length and cholesterol, serum triglycerides, serum low-density lipoprotein, plasma insulin, blood pressure, pulse pressure, or smoking habits. Our data indicate that telomere length is associated with an "obesity-phenotype" but only in women.

Kozakova M, Palombo C, Mhamdi L, Konrad T, Nilsson P, Staehr PB, Paterni M, Balkau B, Anonymous00238. · Department of Internal Medicine, University of Pisa, Pisa, Italy. · Stroke. · Pubmed #17656659 links to  free full text

Abstract: BACKGROUND AND PURPOSE: Regular endurance exercise has been shown to reduce the age-related increase in arterial stiffness that is thought to contribute to cardiovascular risk. The aim of this study was to evaluate the influence of age and habitual physical activity on carotid artery wall thickness and stiffness in a population of young to middle-age subjects at low cardiovascular risk. METHODS: The study population consisted of 432 healthy subjects (166 men; mean+/-SD age, 43+/-8 years; range, 30 to 60 years) free of carotid atherosclerosis and with low coronary heart disease risk, as determined by the Framingham prediction score sheet. All subjects underwent B-mode ultrasonography of the extracranial carotid arteries and physical activity assessment by actigraph, an accelerometer capable of monitoring the intensity and duration of body movements. The intima-media thickness of the common carotid artery was measured on ultrasound images, along with systodiastolic changes in luminal diameter, and indices of carotid stiffness were calculated. RESULTS: Intima-media thickness and carotid stiffness increased with age in both men and women (r=0.24 to 0.52, P<0.001). The magnitude of objectively assessed daily physical activity was negatively related to indices of carotid stiffness (r from -0.20 to -0.25, P<0.001) but not to intima-media thickness. In multivariate regression analyses that included several cardiovascular risk factors such as obesity, blood pressure, plasma lipids, and smoking habits, age and physical activity were independently related to carotid stiffness. CONCLUSIONS: This study provides cross-sectional evidence that habitual physical activity is inversely related to the age-dependent increase in carotid wall stiffness in a young to middle-age population at low risk.

Anonymous00305, Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson Boström K, Isomaa B, Lettre G, Lindblad U, Lyon HN, Melander O, Newton-Cheh C, Nilsson P, Orho-Melander M, Råstam L, Speliotes EK, Taskinen MR, Tuomi T, Guiducci C, Berglund A, Carlson J, Gianniny L, Hackett R, Hall L, Holmkvist J, Laurila E, Sjögren M, Sterner M, Surti A, Svensson M, Svensson M, Tewhey R, Blumenstiel B, Parkin M, Defelice M, Barry R, Brodeur W, Camarata J, Chia N, Fava M, Gibbons J, Handsaker B, Healy C, Nguyen K, Gates C, Sougnez C, Gage D, Nizzari M, Gabriel SB, Chirn GW, Ma Q, Parikh H, Richardson D, Ricke D, Purcell S. · Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA. · Science. · Pubmed #17463246 links to  free full text

Abstract: New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D-in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1-and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.

Hedblad B, Jonsson S, Nilsson P, Engström G, Berglund G, Janzon L. · Department of Community Medicine, Lund University, Malmö University Hospital, Malmö, Sweden. · J Intern Med. · Pubmed #12472916 No free full text.

Abstract: BACKGROUND: People, who are single, have a blue-collar job or low income have an increased cardiovascular risk. This study on myocardial infarction sought to explore whether the socio-economic pattern of disease has any relationship with obesity. METHODS: In the cohort are 20,099 middle-aged men of whom 9,150 were manual and 9,190 nonmanual workers and 1,759 were self-employed. A total of 4,081 were single, 16,018 cohabiting. The body mass index (BMI) cut-off values for overweight and obesity were 25-30 and >/=30 kg m-2, respectively. Local and national registers were used to monitor incidence of events over 18 years. RESULTS: Obesity was associated with an increased incidence of coronary events and deaths in each occupational group. Being single significantly increased the risk associated with obesity. After stratification for civil status the risk associated with obesity was limited to those who were single and who either had a blue-collar job or were self-employed. The multivariate-adjusted relative risk (RR) of coronary events and deaths in obese manual workers who were single was 1.91 (95% confidence interval: 1.21-3.02) and 2.54 (1.74-3.69), respectively, times higher than it was amongst those who were cohabiting. Amongst those who were self-employed, the corresponding age-adjusted RRs were 4.79 (1.69-13.57) and 3.80 (1.62-8.93). CONCLUSIONS: Adjusted for lifestyle and biological risk factors, the increased risk of coronary events and death for obese men with manual jobs was applicable only to those who were single. It is concluded that being single significantly increases the cardiovascular risk associated with obesity.

Balkau B, Charles MA, Drivsholm T, Borch-Johnsen K, Wareham N, Yudkin JS, Morris R, Zavaroni I, van Dam R, Feskins E, Gabriel R, Diet M, Nilsson P, Hedblad B, Anonymous00120. · INSERM Unit 258, Villejuif Cedex, France. · Diabetes Metab. · Pubmed #12461473 links to  free full text

Abstract: BACKGROUND: To describe the frequency, in some European populations, of the World Health Organisation (WHO) defined metabolic syndrome and to compare the frequency of this syndrome with an alternative definition for non-diabetic subjects, called the insulin resistance syndrome proposed by the European Group for the Study of Insulin Resistance (EGIR). METHODS: Investigators of eight European studies contributed, according to a written protocol, the frequencies of abnormalities of these two syndromes, by sex and age class, as well as the overall frequencies of the syndromes and the average number of abnormalities: 8200 men and 9363 women were included. RESULTS: The frequency of both syndromes increased with age and was almost always higher in men than women for a given age. In non-diabetic subjects the frequency of the WHO syndrome varied between 7% and 36% for men 40 to 55 years; for women of the same age, between 5% and 22%. The EGIR syndrome was less frequent than the WHO syndrome (1% to 22% in men, 1% to 14% in women 40-55 years), and in men this was mainly due to the differing definitions of central obesity, as the WHO definition included overall obesity, BMI > or = 30 kg/m(2). CONCLUSIONS: There is great variability in the frequency of the syndrome between different populations, due to the differing frequencies of the abnormalities and no doubt to the differing methodologies of measurement. Prospective studies and advances in the knowledge of physio-pathological mechanisms are required to determine the most appropriate and practical definition of the syndrome.

Nilsson P, Berglund G. · Klinisk forskningsenhet medicin, Universitetssjukhuset MAS, Malmö. · Lakartidningen. · Pubmed #12219468 No free full text.

This publication has no abstract.

Jonsson S, Hedblad B, Engström G, Nilsson P, Berglund G, Janzon L. · Department of Community Medicine, Malmö University Hospital, Malmö, Sweden. · Int J Obes Relat Metab Disord. · Pubmed #12119569 links to  free full text

Abstract: OBJECTIVE: To assess to what extent the incidence of coronary events and death related to smoking, hypertension, hyperlipidemia and diabetes is modified by obesity. DESIGN: Prospective cohort study. SUBJECTS: A total of 22 025 men aged 27 to 61-y-old at entry. MEASUREMENTS: Incidence of coronary events (CE, ie acute myocardial infarctions and deaths due to chronic ischaemic heart disease) and death during 23 y of follow-up was studied in relation to body mass index (BMI), heart rate, blood pressure, blood lipids, glucose and insulin, lifestyle factors, history of angina pectoris, history of cancer, self-reported health and socio-economic conditions. RESULTS: At the end of follow-up 20% of the obese men were no longer alive, and 13% had had a coronary event. Incidence of CE was 16% lower (RR (relative risk) 0.84; 95% confidence interval (CI) 0.65-1.10) among underweight (n=1171), 24% higher (RR 1.24; CI 1.12-1.37) among overweight (n=7773), and 76% higher (RR 1.76; 95% CI 1.49-2.08) among obese men (n=1343) than it was among men with normal BMI (n=11 738). The risk associated with overweight and obesity remained statistically significant after adjustment for potential confounders (RR 1.18; CI 1.07-1.31; and 1.39; 1.17-1.65, respectively). The association between BMI and mortality was J-shaped. In all, 1.7% of the obese men were smokers with hypertension, hyperlipidaemia and diabetes, 16.3% were not exposed to any of these risk factors. The cardiovascular risk associated with obesity was small in the absence of other risk factors. Between smoking and obesity there was a statistically significant synergistic effect. CONCLUSIONS: Obesity is associated with an increased incidence of coronary events and death. The risk associated with obesity is substantially increased by exposure to other atherosclerotic risk factors, of which smoking seems to be the most important. The preventive potential of these associations should be evaluated in controlled trials.

Hedblad B, Nilsson P, Engström G, Berglund G, Janzon L. · Department of Medicine and Department of Community Medicine, Lund University, Malmö University Hospital, Malmö, Sweden. · Diabet Med. · Pubmed #12060058 No free full text.

Abstract: AIMS: To compare the incidence of myocardial infarction and death in non-diabetic subjects with and without insulin resistance. METHODS: Population-based prospective cohort study, in Malmö, Sweden, of 4748 non-diabetic subjects (60% women), aged 46-68 years, with no history of myocardial infarction or stroke. The prevalence of insulin resistance was established by the homeostasis model assessment (HOMA) and defined as values above the sex-specific 75th percentile (1.80 for women and 2.12 for men). Incidence of myocardial infarction and death is based on record linkage with local and national registers. Cox's proportional hazards model was used to assess the influence of insulin resistance after adjustment for age, sex, hyperglycaemia, raised arterial blood pressure, dyslipidaemia, central obesity, smoking and leisure-time physical activity. RESULTS: Sixty-two subjects suffered a coronary event, and 93 subjects died during the 6-year follow-up period. Insulin resistance was after adjustment for other factors included in the insulin resistance syndrome and other potential confounders, associated with an increased incidence of coronary events (relative risk (RR) 2.18; 95% confidence interval (CI) 1.22-3.87; P = 0.008) and deaths (RR 1.62; 1.03-2.55; P = 0.038). CONCLUSIONS: Insulin resistance, as assessed by the HOMA method, was in this cohort of middle-aged non-diabetic subjects associated with an increased incidence of myocardial infarction and death. This risk remained when smoking, low physical activity and factors included in the insulin resistance syndrome were taken into account in a stepwise regression model.

Nilsson P, Nilsson JA, Lindgärde F. · Avdelningen för medicin, Universitetssjukhuset MAS, Malmö. · Lakartidningen. · Pubmed #10881529 No free full text.

This publication has no abstract.