We found evidence for plasticity in metabolic rate by avoiding to freeze compared with cold-exposure in a randomized setting in non-selected humans.

BackgroundNew and clinically useful markers of cardiovascular risk are of essence in type 2 diabetes since ischemic heart disease is a major cause of death in these patients.MethodsWe analyzed baseline data from 476 men and 244 women who participated in “Cardiovascular Risk factors in Patients with Diabetes -a Prospective study in Primary care” study. All participants had type 2 diabetes and were 55-66 years old at recruitment during year 2005 to 2008. Except for established traditional risk markers for vascular disease, we also estimated vascular complications non-invasively by performance of carotid-femoral pulse-wave velocity (PWV, with applanation-tonometry) and intima-media thickness of carotid arteries (IMT, with B-mode ultrasound). Patients were followed for incidence of ischemic heart disease mortality and morbidity until end of the year 2012, using the national Swedish Cause of Death and Hospitalization Registries.ResultsDuring the follow-up period of a median of 6 years 47 men and 10 women died or were hospitalized for ischemic heart disease including myocardial infarction. Leptin levels were positively related to the hazard ratio (HR) in men (HR for each log 10 unit 4.9, CI 1.99 to 11.8) and women (HR 11.5, CI 1.47 to 89.7). Leptin predicted ischemic heart disease independently of age, HbA1c, BMI, systolic blood pressure and LDL-cholesterol/HDL-cholesterol ratio (men: HR 12.9 CI 3.2-53, women: HR 19.9, CI 1.2-327) This finding of increased risk related to high leptin levels was also statistically significant when carotid-femoral PWV and IMT were both added to the equations in men (hazard ratio 9.2 CI 2.1-41).ConclusionsOur data support the use of serum leptin in type 2 diabetes to add independent prognostic information in terms of ischemic heart disease when compared with traditional cardiovascular risk factors. In the men of the cohort this prognostic information was in addition also to data on IMT and PWV, two non-invasive measurements of the extent of vascular disease. The power to detect a similar relationship in women was less strong due to lower incidence of cardiovascular disease.Trial registrationClinicalTrials.gov: NCT01049737.

We aimed to discover novel associations between leptin and circulating proteins which could link leptin to the development of cardiovascular disease in patients with type 2 diabetes (T2DM). In a discovery phase, we investigated associations between 88 plasma proteins, assessed with a proximity extension assay, and plasma leptin in a cohort of middle-aged patients with T2DM. Associations passing the significance threshold of a False discovery rate of 5% (corresponding to p < 0.0017) were replicated in patients with T2DM in an independent cohort. We also investigated if proteins mediated the longitudinal association between plasma leptin and the incidence of major cardiovascular events (MACE). One protein, adipocyte fatty acid binding protein (A-FABP), was significantly associated with leptin in both the discovery phase [95% CI (0.06, 0.17) p = 0.00002] and the replication cohort [95% CI (0.12, 0.39) p = 0.0003]. Multiplicative interaction analyses in the two cohorts suggest a stronger association between A-FABP and leptin in men than in women. In longitudinal analyses, the association between leptin and MACE was slightly attenuated after adding A-FABP to the multivariate model. Our analysis identified a consistent association between leptin and A-FABP in two independent cohorts of patients with T2DM, particularly in men. Trial registration: ClinicalTrials.gov identifier NCT 01049737. Abbreviations ADM Adrenomedullin A-FABP Adipocyte fatty acid binding protein BMI Body mass index CARDIPP Cardiovascular risk factors in patients with diabetes-a prospective study in primary care CHD Coronary heart disease CRP C-reactive protein CVD Cardiovascular disease HDL High density lipoprotein HR Hazard ratio LDL Low density lipoprotein LOD Limit of detection MACE Major adverse cardiac events PCR Polymerase chain reaction

Background We used a multiplex proteomics assay with the aim to discover novel associations between leptin and 88 circulating proteins in order to provide additional insights into the role of leptin in the development of CVD in patients with type 2 diabetes (T2DM). Material and methods In a discovery phase, we investigated associations between 88 plasma proteins, assessed with a proximity extension assay, and plasma leptin in a cohort of middle-aged patients with T2DM (CARDIPP, n=661). Associations that passed the significance threshold of a False discovery rate of 5% (corresponding to p <0.0017) were replicated in diabetes patients in an independent cohort (PIVUS, n=116). We also investigated if proteins mediated the longitudinal association between plasma leptin and the incidence of major cardiovascular events (MACE). Results Two proteins were significantly associated with leptin in the discovery phase, adipocyte fatty acid binding protein (A-FABP) (regression coefficient .118, 95% CI (.064, .173) p =0.000024) and adrenomedullin ( p =0.000002) but only A-FABP was significantly associated with leptin in the replication cohort (regression coefficient .0254, 95% CI (.119, .39) p =0.0003). Multiplicative interaction analyses in the two cohorts suggest a stronger association between A-FABP and leptin in men than in women. In longitudinal analyses, the association between leptin and MACE was slightly attenuated after adding A-FABP to the multivariate model. Conclusions Our analysis identified a consistent association between leptin and A-FABP in two independent cohorts of patients with T2DM, particularly in men. Our data encourage future large-scale proteomics analyses for additional insights into leptin biology.

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