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Spegel P.,Lund University | Ekholm E.,Lund University | Tuomi T.,Folkhalsan Research Center | Tuomi T.,University of Helsinki | And 3 more authors.
Diabetes | Year: 2013

Mutations in the gene encoding glucokinase (GCK) cause a mild hereditary form of diabetes termed maturity-onset diabetes of the young (MODY)2 or GCK-MODY. The disease does not progress over time, and diabetes complications rarely develop. It has therefore been suggested that GCK-MODY represents a metabolically compensated condition, but experimental support for this notion is lacking. Here, we profiled metabolites in serum from patients with MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), and type 2 diabetes and from healthy individuals to characterize metabolic perturbations caused by specific mutations. Analysis of four GCK-MODY patients revealed a metabolite pattern similar to that of healthy individuals, while other forms of diabetes differed markedly in their metabolite profiles. Furthermore, despite elevated glucose concentrations, carriers of GCK mutations showed lower levels of free fatty acids and triglycerides than healthy control subjects. The metabolite profiling was confirmed by enzymatic assays and replicated in a cohort of 11 GCK-MODY patients. Elevated levels of fatty acids are known to associate with β-cell dysfunction, insulin resistance, and increased incidence of late complications. Our results show that GCK-MODY represents a metabolically normal condition, which may contribute to the lack of late complications and the nonprogressive nature of the disease. © 2013 by the American Diabetes Association. Source


Oh J.-K.,Karolinska Institutet | Oh J.-K.,National Cancer Control Institute | Weiderpass E.,Karolinska Institutet | Weiderpass E.,Folkhalsan Research Center | Weiderpass E.,University of Tromso
Annals of Global Health | Year: 2014

Background Infection is one of the main risk factors for cancer. Objectives Epidemiology, pathogenesis, and disease burden of infection-related cancers were reviewed by infectious agents. Findings Chronic infection with Epstein-Barr virus, hepatitis B and C viruses, Kaposi sarcoma herpes virus, human immunodeficiency virus (HIV) type 1, human papillomavirus (HPV), human T-cell lymphotropic virus type 1, Helicobacter pylori, Clonorchis sinensis, Opisthorchis viverrini, and Schistosoma haematobium are associated with nasopharyngeal carcinoma; lymphoma and leukemia, including non-Hodgkin lymphoma, Hodgkin lymphoma, and Burkitt lymphoma; hepatocellular carcinoma; Kaposi sarcoma; oropharyngeal carcinoma; cervical carcinoma and carcinoma of other anogential sites; adult T-cell leukemia/lymphoma; gastric carcinoma; cholangiocarcinoma; and urinary bladder cancer. In 2008, approximately 2 million new cancer cases (16%) worldwide were attributable to infection. If these infections could be prevented and/or treated, it is estimated that there would be about 23% fewer cancers in less developed regions of the world, and about 7% fewer cancers in more developed regions. Conclusion Widespread application of existing public health methods for the prevention of infection, such as vaccination, safer injection practices, quality-assured screening of all donated blood and blood components, antimicrobial treatments, and safer sex practices, including minimizing one's lifetime number of sexual partners and condom use, could have a substantial effect on the future burden of cancer worldwide. © 2014 Icahn School of Medicine at Mount Sinai. Source


Eriksson J.G.,Finnish National Institute for Health and Welfare | Eriksson J.G.,University of Helsinki | Eriksson J.G.,Folkhalsan Research Center
American Journal of Clinical Nutrition | Year: 2011

A slow rate of intrauterine growth is a major risk factor for several common noncommunicable diseases, which include the following: coronary heart disease (CHD), hypertension, and type 2 diabetes. Likewise, growth patterns in infancy and childhood have been identified as important factors linked to the pathogenesis of these disorders. In this overview, patterns of growth associated with CHD, type 2 diabetes, and related metabolic traits in adult life are presented on the basis of findings from the Helsinki Birth Cohort Study (HBCS) 1934-1944. Later risk of CHD was associated with small body size at birth and during infancy, followed by an increase in body size later in childhood. This pattern of growth has been associated with dyslipidemia in later life, which offers an explanation for the observed findings. Type 2 diabetes and CHD share several risk factors. The early growth of persons who later develop type 2 diabetes includes a small body size at birth as well as a small body size during infancy. An early age at adiposity rebound was associated with a markedly increased risk of type 2 diabetes in adulthood. The patterns of growth associated with type 2 diabetes are also associated with alterations in body composition, which predisposes to insulin resistance and the metabolic syndrome. The presented findings suggest that to be able to understand the pathogenesis of several noncommunicable diseases, the diseases need to be studied from a life-course perspective, and prenatal and childhood growth as well as adult characteristics need to be taken into account. © 2011 American Society for Nutrition. Source


Tuomikoski P.,University of Helsinki | Mikkola T.S.,University of Helsinki | Mikkola T.S.,Folkhalsan Research Center
Annals of Medicine | Year: 2014

In women, cardiovascular disease (CVD) accounts for about half of all deaths in Western countries. It is generally accepted that endogenous estrogen protects premenopausal women from CVD. However, whether postmenopausal hormone therapy (HT) confers cardiovascular benefit or harm remains controversial. One of the most pronounced factors modifying the cardiovascular effects of HT is age or time since menopause at the initiation of HT. Recently also the impact of hot flushes on CVD risk and the outcomes of HT has gained attention. This review summarizes the newest data regarding HT and CVD in recently postmenopausal women aged 50-59 years in light of the results from older HT trials. The aim is to help clinicians counsel their patients regarding the individual risks and benefits associated with HT use in this age group, where HT use is most prevalent. © 2014 Informa UK, Ltd. Source


Knip M.,University of Helsinki | Knip M.,Folkhalsan Research Center | Knip M.,University of Tampere
Diabetologia | Year: 2012

This edition of 'Then and now' discusses the valuable contribution made by Onkamo and colleagues to the field of type 1 diabetes epidemiology in their widely cited paper 'Worldwide increase in incidence of type I diabetes - The analysis of the data on published incidence trends', which was published 13 years ago (Diabetologia 1999;42:1395-1403). At the time, this represented the most extensive analysis of global trends in the epidemiology of type 1 diabetes, and covered/included a considerably larger geographical area than previous studies. The data confirmed that there was a worldwide increase in the incidence of childhood diabetes during the second half of the 20th century. Predictions made by the group for the incidence rates in 2010 pointed to large increases, but in retrospect these turned out to be too conservative, particularly among younger children. Whether the increase in incidence among children aged < 15 years has started to level off is unknown. Looking to the future, more data on the epidemiology of type 1 diabetes over the whole lifespan are definitely needed. In addition, descriptive epidemiology needs to be complemented with 'aetiological' epidemiology generating information on the causes of the incidence and prevalence trends. © 2012 Springer-Verlag. Source

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