Stefan Söderberg

Leptin is associated with increased risk of myocardial infarction

Abstract. Söderberg S, Ahrén B, Jansson J‐H, Johnson O, Hallmans G, Asplund K, Olsson T (Umeå University, Umeå; and Lund University, Malmö, Sweden). Leptin is associated with increased risk of myocardial infarction. J Intern Med 1999; 246: 409–418.

Obesity and colon cancer: Does leptin provide a link?

Obesity, a risk factor for colorectal cancer, is associated with elevated serum levels of leptin, the adipocyte‐derived hormone, and insulin. Experimental and epidemiologic studies have indicated a role for insulin in the pathogenesis of colon cancer, and recent experimental studies have suggested a similar role for leptin. In a case‐control study nested in the Janus Biobank, Norway, we measured serum levels of leptin and C‐peptide (a marker of pancreatic insulin secretion) in cryopreserved prediagnostic sera from men (median age, 45 years) who were diagnosed with cancer of the colon (n = 235) or rectum (n = 143) after blood collection (median time, 17 years), and among 378 controls matched for age and date of blood collection. Conditional logistic regression analyses showed an approximately 3‐fold increase in colon cancer risk with increasing concentrations of leptin up to an odds ratio (OR) of 2.72 (95% CI = 1.44–5.12) for top vs. bottom quartile (ptrend = 0.008). The corresponding OR for C‐peptide was 1.81 (95% CI = 0.67–4.86; ptrend = 0.19). The risk estimates remained unchanged after mutual adjustment. No association of hormone levels with rectal cancer risk was found. Reproducibility of hormone measurements assessed by intraclass coefficients (ICCs) for paired samples taken 1 year apart was high for leptin (ICC = 0.82) but lower for C‐peptide (ICC = 0.30). Our results suggest that leptin is a risk factor for colon cancer, and that leptin may provide a link between obesity and colon cancer. Leptin may be directly involved in colon tumorigenesis or it may serve as a sensitive and robust marker of an obesity‐induced adverse endocrine environment. Only weak support for an association of insulin with colon cancer was found.

High Prevalence of Chlamydia pneumoniae DNA in Peripheral Blood Mononuclear Cells in Patients with Cardiovascular Disease and in Middle-Aged Blood Donors

Nested polymerase chain reaction (nPCR) demonstrated the presence of Chlamydia pneumoniae-specific DNA in peripheral blood mononuclear cells (PBMC). PBMC samples were obtained from 103 consecutive patients (62 male, 41 female) aged 22-85 years (mean, 64) admitted for coronary angiography because of suspected coronary heart disease and from 52 blood donors (43 male, 9 female) aged 40-64 years (mean, 49). Of the 101 evaluable patients, 60 (59%) were identified by nPCR assay as C. pneumoniae DNA carriers; C. pneumoniae-specific microimmunofluorescence (MIF) serology confirmed exposure to the bacterium in 57 (95%) of the 60 nPCR-positive patients. Among the 52 blood donors, the nPCR assay identified 24 (46%) C. pneumoniae DNA carriers, all of whom were positive by C. pneumoniae-specific serology. Thirty-two patients (32%) and 23 blood donors (44%) were MIF antibody-positive but repeatedly nPCR-negative; Bartonella henselae- or Bartonella quintana-specific antibodies were not detected among any of these subjects. In this study, C. pneumoniae DNA was common in PBMC of patients with coronary heart disease and in middle-aged blood donors.

Prospective study of IGF-I, IGF-binding proteins, and breast cancer risk, in northern and southern Sweden.

Objective: To examine the possible relationships of breast cancer risk to prediagnostic plasma levels of insulin; insulin-like growth factor-I (IGF-I); and IGF-binding proteins -1, -2, and -3. Methods: Within two prospective cohorts in Umeå and Malmö we measured plasma concentrations of insulin, IGF-I, and IGFBPs for a total of 513 incident breast cancer cases and 987 matched controls. Results: Globally, risk was unassociated with levels of IGF-I, IGFBP-3, or IGF-I adjusted for IGFBP-3. When breaking down the analysis by subgroups of age at blood donation, an increase in risk was observed for increasing levels of IGF-I in women aged 55 or older, in the Umeå cohort only (odds ratios of 1.00, 1.73, 1.76, 1.90; ptrend = 0.05). This effect weakened, however, when the analysis was restricted to subjects who did not use exogenous hormones for the treatment of menopausal symptoms. Levels of IGF-I and IGFBP-3 were not related to risk in younger women, recruited before age 50, contrary to observations from previous studies. In a subcohort where blood samples had been collected after at least four hours of fasting, breast cancer risk showed no clear associations with levels of insulin, IGFBP-1, or IGFBP-2. Conclusions: Our results do not confirm earlier findings of an association of plasma IGF-I levels with breast cancer risk especially in young women, but suggest a possible association with postmenopausal breast cancer risk, possibly among ERT/HRT users only. Our results do not support the hypothesis that elevated plasma insulin levels, and reduced levels of IGFBP-1 and IGFBP-2, are associated with increased breast cancer risk.

Cardiovascular disease and diabetes in the Northern Sweden Health and Disease Study Cohort - evaluation of risk factors and their interactions.

The purpose of this paper is, first, to describe the organization, sampling procedures, availability of samples/database, ethical considerations, and quality control program of the Northern Sweden Health and Disease Study Cohort. Secondly, some examples are given of studies on cardiovascular disease and diabetes with a focus on the biomarker programme. The cohort has been positioned as a national and international resource for scientific research.

Leptin, but not adiponectin, predicts stroke in males

Objective.  To test whether leptin and adiponectin are risk markers for a first‐ever stroke.

Independent effects of obesity and cortisol in predicting cardiovascular risk factors in men and women

Abstract. Walker BR, Soderberg S, Lindahl B, Olsson T (University of Edinburgh, Western General Hospital, Edinburgh, UK and the University of Umea, University Hospital, Umea, Sweden). Independent effects of obesity and cortisol in predicting cardiovascular risk factors in men and women. J Intern Med 2000; 247: 198–204.

Intra-adipose sex steroid metabolism and body fat distribution in idiopathic human obesity

Objective  Causes of visceral fat accumulation include glucocorticoid excess or decreased oestrogen/androgen ratio either in plasma or within adipose tissue. In obese subjects, the intra‐adipose cortisol‐generating enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) is increased, but information on sex steroid signalling is sparse. We aimed to test associations between body fat or fat distribution and mRNA transcript levels for androgen and oestrogen receptors and for enzymes metabolizing sex steroids in adipose tissue.

Large improvements in major cardiovascular risk factors in the population of northern Sweden: the MONICA study 1986–2009

Abstract.  Eriksson M, Holmgren L, Janlert U, Jansson J‐H, Lundblad D, Stegmayr B, Söderberg S, Eliasson M (Department of Public Health and Clinical Medicine, Umeå University, Umeå; Research Department, Norrbotten County Council, Luleå; Department of Medicine, Skellefteå Hospital, Skellefteå; Department of Medicine, Sunderby Hospital, Luleå; and National Board of Health and Welfare, Stockholm, Sweden). Large improvements in major cardiovascular risk factors in the population of northern Sweden: the MONICA study 1986–2009. J Intern Med 2011; 269: 219–231.

Central Obesity as a Precursor to the Metabolic Syndrome in the AusDiab Study and Mauritius

Evidence from epidemiologic studies that central obesity precedes future metabolic change and does not occur concurrently with the appearance of the blood pressure, glucose, and lipid abnormalities that characterize the metabolic syndrome (MetS) has been lacking. Longitudinal surveys were conducted in Mauritius in 1987, 1992, and 1998, and in Australia in 2000 and 2005 (AusDiab). This analysis included men and women (aged ≥25 years) in three cohorts: AusDiab 2000–2005 (n = 5,039), Mauritius 1987–1992 (n = 2,849), and Mauritius 1987–1998 (n = 1,999). MetS components included waist circumference, systolic blood pressure, fasting and 2‐h postload plasma glucose, high‐density lipoprotein (HDL) cholesterol, triglycerides, and homeostasis model assessment of insulin sensitivity (HOMA‐S) (representing insulin sensitivity). Linear regression was used to determine which baseline components predicted deterioration in other MetS components over 5 years in AusDiab and 5 and 11 years in Mauritius, adjusted for age, sex, and ethnic group. Baseline waist circumference predicted deterioration (P < 0.01) in four of the other six MetS variables tested in AusDiab, five of six in Mauritius 1987–1992, and four of six in Mauritius 1987–1998. In contrast, an increase in waist circumference between baseline and follow‐up was only predicted by insulin sensitivity (HOMA‐S) at baseline, and only in one of the three cohorts. These results suggest that central obesity plays a central role in the development of the MetS and appears to precede the appearance of the other MetS components.