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Diabetes in Europe: An update

  • T. Tamayo
    Affiliations
    Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
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  • J. Rosenbauer
    Affiliations
    Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
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  • S.H. Wild
    Affiliations
    Centre for Population Health Sciences, University of Edinburgh, UK
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  • A.M.W. Spijkerman
    Affiliations
    Centre for Nutrition, Prevention and Health Services, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands
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  • C. Baan
    Affiliations
    Centre for Nutrition, Prevention and Health Services, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands
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  • N.G. Forouhi
    Affiliations
    Medical Research Council Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
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  • C. Herder
    Affiliations
    Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
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  • W. Rathmann
    Correspondence
    Corresponding author at: Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Auf’m Hennekamp 65, 40225 Düsseldorf, Germany. Tel.: +49 211 33 82 663; fax: +49 211 33 82 677.
    Affiliations
    Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
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Published:December 03, 2013DOI:https://doi.org/10.1016/j.diabres.2013.11.007

      Abstract

      Diabetes is among the leading causes of death in the IDF Europe Region (EUR), continues to increase in prevalence with diabetic macro- and microvascular complications resulting in increased disability and enormous healthcare costs. In 2013, the number of people with diabetes is estimated to be 56 million in EUR with an overall estimated prevalence of 8.5%. However, estimates of diabetes prevalence in 2013 vary widely in the 56 diverse countries in EUR from 2.4% in Moldova to 14.9% in Turkey. Trends in diabetes prevalence also vary between countries with stable prevalence since 2002 for many countries but a doubling of diabetes prevalence in Turkey. For 2035, a further increase of nearly 10 million people with diabetes is projected for the EUR. Prevalence of type 1 has also increased over the past 20 years in EUR and there was estimated to be 129,350 cases in children aged 0–14 years in 2013. Registries provide valid information on incidence of type 1 diabetes with more complete data available for children than for adults.
      There are large differences in distribution of risk factors for diabetes at the population level in EUR. Modifiable risk factors such as obesity, physical inactivity, smoking behaviour (including secondhand smoking), environmental pollutants, psychosocial factors and socioeconomic deprivation could be tackled to reduce the incidence of type 2 diabetes in Europe.
      In addition, diabetes management is a major challenge to health services in the European countries. Improved networking practices of health professionals and other stakeholders in combination with empowerment of people with diabetes and continuous quality monitoring need to be further developed in Europe.

      Keywords

      1. Introduction

      Diabetes is one of the most challenging health problems in the 21st century in the IDF Europe Region (EUR). It is among the leading causes of death and diabetic macro- and microvascular complications are resulting in increased disability and enormous healthcare costs. This increase will place an enormous financial burden on a declining working age population in Europe. Despite the increasing prevalence and the human and economic burden, valid epidemiological data on diabetes are scarce in EUR. While infectious diseases are carefully monitored, this non-communicable disease is usually not required to be continuously registered. The aim of this review is to comment on the population-based data on diabetes [
      IDF Diabetes Atlas.
      ] and diabetes-related complications in Europe published by the IDF Diabetes Atlas, and to discuss the possible impact of risk factors on geographic variation within Europe.

      2. Diabetes epidemiology

      2.1 Type 2 diabetes

      2.1.1 Prevalence estimates: heterogeneity of results and time trends

      The IDF Europe Region includes 56 diverse countries from the Russian Federation in the northeast, Kazakhstan in the east, Iceland in the northwest to Portugal in the southwest. The countries vary markedly in size, language, ethnic groups and affluence. Diabetes prevalence in the European countries is similarly heterogeneous with an age-standardised comparative prevalence ranging from 2.4% in Moldova to 14.9% in Turkey in 2013. Overall, the raw prevalence of diabetes in EUR in 2013 is estimated to be 8.5%, which corresponds to 56 million cases (age 20–79 years) and an age-standardised prevalence of 6.8% (type 1 and type 2 diabetes – known and undiagnosed). The estimated proportion of undiagnosed diabetes ranged from 29.3% in European low-income countries (EUR-LIC: e.g. Kyrgyzstan, Uzbekistan) to 36.6% in European high-income countries (EUR-HIC: e.g. Denmark, Finland, United Kingdom (UK)).
      The highest age-standardised diabetes prevalence in EUR was estimated for Turkey with 14.9%, based on a population-based survey performed in 2010 (TURDEP II) that included comprehensive phenotyping and diabetes diagnosis according to WHO guidelines (1999) – the gold standard for epidemiologic studies [
      • Satman I.
      • Omer B.
      • Tutuncu Y.
      • Kalaca S.
      • Gedik S.
      • Dinccag N.
      • et al.
      TURDEP-II Study Group. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults.
      ,
      • World Health Organisation
      Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. Report of a WHO consultation.
      ]. Turkey has also experienced the highest increase in diabetes [
      • Satman I.
      • Yilmaz T.
      • Sengül A.
      • Salman S.
      • Salman F.
      • Uygur S.
      • et al.
      Population-based study of diabetes and risk characteristics in Turkey: results of the Turkish diabetes epidemiology study (TURDEP).
      ,
      • Whiting
      • Guariguata L.
      • Weil C.
      • Shaw J.
      IDF Diabetes Atlas: global estimates of the prevalence of diabetes for 2011 and 2030.
      ]. While the prevalence was estimated at 7.5% in the 2011 IDF-Atlas, the estimate for 2013 was almost twice as high. These estimates are based on two surveys (TURDEP-I and -II) using similar methods [
      • Satman I.
      • Omer B.
      • Tutuncu Y.
      • Kalaca S.
      • Gedik S.
      • Dinccag N.
      • et al.
      TURDEP-II Study Group. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults.
      ,
      • Satman I.
      • Yilmaz T.
      • Sengül A.
      • Salman S.
      • Salman F.
      • Uygur S.
      • et al.
      Population-based study of diabetes and risk characteristics in Turkey: results of the Turkish diabetes epidemiology study (TURDEP).
      ]. However, TURDEP-I used the 1985 WHO protocol for diabetes diagnosis [
      • World Health Organization
      Diabetes mellitus: report of a WHO Study Group.
      ] while TURDEP-II used the 1999 WHO protocol. The diabetes prevalence in TURDEP-II would have been approximately 3% lower if the 1985 WHO criteria had been used. Other explanations for the steep increase in diabetes prevalence during the 12 years between the studies include: an increase in life expectancy of 4–5 years [
      • World Health Organization
      World health statistics 2011.
      ], a longer survival of patients with type 2 diabetes, and changes in lifestyle. Furthermore, the mean BMI increased between surveys from 26.6 to 28.6 kg/m2 and mean waist circumference from 87.2 to 94.5 cm [
      • Satman I.
      • Omer B.
      • Tutuncu Y.
      • Kalaca S.
      • Gedik S.
      • Dinccag N.
      • et al.
      TURDEP-II Study Group. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults.
      ]. Unfortunately, updated surveys were available only for Turkey, Germany and Spain to describe changes in diabetes prevalence. In Germany, estimates for known diabetes increased by 38% from 4.7% to 5.6% between two nationwide surveys with a high comparability conducted in 1998 and 2012 [
      • Thefeld W.
      Prevalence of diabetes mellitus in the adult German population.
      ,
      • Heidemann C.
      • Du Y.
      • Schubert I.
      • Rathmann W.
      • Scheidt-Nave C.
      Prävalenz und zeitlicheEntwicklung des bekannten Diabetes mellitus.
      ]. Of the 38% increase, 14% were explained by demographic changes but 24% remained unexplained. For Spain, a new nationwide survey using OGTT was utilised to generate the estimates for 2013 [
      • Soriguer F.
      • Goday A.
      • Bosch-Comas A.
      • Bordiú E.
      • Calle-Pascual A.
      • Carmena R.
      • et al.
      Prevalence of diabetes mellitus and impaired glucose regulation in Spain: the diabetes study.
      ]. The prevalence estimates for Spain increased from 8.1% to 10.8% from the 2011 to the 2013 Atlas editions [
      IDF Diabetes Atlas.
      ,
      IDF Diabetes Atlas.
      ]. In contrast, the selection of a nationwide source [
      • Pajak A.
      Myocardial infarction and complications longitudinal observation of a population of 280,000 women and men – Project POL-MONICA Krakow. I. Genesis and objectives of the WHO MONICA Project.
      ] instead of two regional databases [
      • Łopatyński J.
      • Mardarowicz G.
      • Nicer T.
      • Szcześniak G.
      • Król H.
      • Matej A.
      • et al.
      The prevalence of type II diabetes mellitus in rural urban population over 35 years of age in Lublin region (Eastern Poland).
      ,
      • Polakowska M.
      • Piotrowski W.
      Incidence of diabetes in the Polish population: results of the Multicenter Polish Population Health Status Study – WOBASZ.
      ] for the current edition resulted in a considerably lower prevalence estimate in Poland (6.5% compared to a previous estimate of 10.6%). For many countries including Portugal, France, Italy, Switzerland, Hungary, Albania, Russian Federation and Uzbekistan the databases and estimates remained almost unchanged since the last estimates in 2011, largely because few new studies have been published in those countries [
      • Gardete-Correia L.
      • Boavida J.M.
      • Raposo J.F.
      • Mesquita A.C.
      • Fona C.
      • Carvalho R.
      • et al.
      First diabetes prevalence study in Portugal: PREVADIAB study.
      ,
      • Gourdy P.
      • Ruidavets J.B.
      • Ferrieres J.
      • Ducimetiere P.
      • Amouyel P.
      • Arveiler D.
      • et al.
      Prevalence of type 2 diabetes and impaired fasting glucose in the middle-aged population of three French regions – the MONICA study 1995–97.
      ,
      • Bringer J.
      • Fontaine P.
      • Detournay B.
      • Nachit-Ouinekh F.
      • Brami G.
      • Eschwege E.
      Prevalence of diagnosed type 2 diabetes mellitus in the French general population: the INSTANT study.
      ,
      • Bonaldi C.
      • Vernay M.
      • Roudier C.
      • Salanave B.
      • Oleko A.
      • Malon A.
      • et al.
      A first national prevalence estimate of diagnosed and undiagnosed diabetes in France in 18- to 74-year-old individuals: the French Nutrition and Health Survey 2006/2007.
      ,
      • Cricelli C.
      • Mazzaglia G.
      • Samani F.
      • Marchi M.
      • Sabatini A.
      • Nardi R.
      • et al.
      Prevalence estimates for chronic diseases in Italy: exploring the differences between self-report and primary care databases.
      ,
      • Estoppey D.
      • Paccaud F.
      • Vollenweider P.
      • Marques-Vidal P.
      Trends in self-reported prevalence and management of hypertension, hypercholesterolemia and diabetes in Swiss adults, 1997–2007.
      ,
      • Vamos E.P.
      • Kopp M.S.
      • Keszei A.
      • Novak M.
      • Mucsi I.
      Prevalence of diabetes in a large, nationally representative population sample in Hungary.
      ,
      • Doupis J.
      • Tentolouris N.
      • Mastrokostopoulos A.
      • Kokkinos A.
      • Doupis C.
      • Zdrava A.
      • et al.
      Prevalence of type 2 diabetes in the southwest Albanian adult population.
      ,
      • Dogadin S.A.
      • Mashtakov B.P.
      • Taranushenko T.E.
      Prevalence of type 2 diabetes in northern populations of Siberia.
      ,
      • King H.
      • Abdullaev B.
      • Djumaeva S.
      • Nikitin V.
      • Ashworth L.
      • Dobo M.G.
      Glucose intolerance and associated factors in the Fergana Valley, Uzbekistan.
      ].

      2.1.2 Undiagnosed diabetes

      Lack of nationwide data for estimating the prevalence of known type 2 diabetes is still apparent in Europe, especially for many eastern European countries. Overall, nationwide data were available for only 34 (61%) of all 56 countries [
      IDF Diabetes Atlas.
      ]. However, most striking was the paucity of nationwide studies that used the WHO 1999 protocol for estimating undiagnosed diabetes. In total, only four studies selected for analysis (from Turkey, Spain, Portugal and Finland) used this gold standard for epidemiologic studies that included measurements of fasting plasma glucose and 2h-glucose [
      • Satman I.
      • Omer B.
      • Tutuncu Y.
      • Kalaca S.
      • Gedik S.
      • Dinccag N.
      • et al.
      TURDEP-II Study Group. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults.
      ,
      • Soriguer F.
      • Goday A.
      • Bosch-Comas A.
      • Bordiú E.
      • Calle-Pascual A.
      • Carmena R.
      • et al.
      Prevalence of diabetes mellitus and impaired glucose regulation in Spain: the diabetes study.
      ,
      • Gardete-Correia L.
      • Boavida J.M.
      • Raposo J.F.
      • Mesquita A.C.
      • Fona C.
      • Carvalho R.
      • et al.
      First diabetes prevalence study in Portugal: PREVADIAB study.
      ,
      • Saaristo T.E.
      • Barengo N.C.
      • Korpi-Hyövälti E.
      • Oksa H.
      • Puolijoki H.
      • Saltevo J.T.
      • et al.
      High prevalence of obesity, central obesity and abnormal glucose tolerance in the middle-aged Finnish population.
      ]. Other methods, based on fasting glucose measurement alone, can underestimate the prevalence of unknown type 2 diabetes (DECODE) [
      • DECODE Study Group
      Age- and sex-specific prevalences of diabetes and impaired glucose regulation in 13 European cohorts.
      ]. In the 2013 IDF Diabetes Atlas, the proportion of undiagnosed diabetes ranged from 20% based on HbA1c [
      • Gardete-Correia L.
      • Boavida J.M.
      • Raposo J.F.
      • Mesquita A.C.
      • Fona C.
      • Carvalho R.
      • et al.
      First diabetes prevalence study in Portugal: PREVADIAB study.
      ], 30% based on FPG [
      • Metelko Z.
      • Pavlić-Renar I.
      • Poljicanin T.
      • Szirovitza L.
      • Turek S.
      Prevalence of diabetes mellitus in Croatia.
      ], to 44–61% based on OGTT [
      • Satman I.
      • Omer B.
      • Tutuncu Y.
      • Kalaca S.
      • Gedik S.
      • Dinccag N.
      • et al.
      TURDEP-II Study Group. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults.
      ,
      • Soriguer F.
      • Goday A.
      • Bosch-Comas A.
      • Bordiú E.
      • Calle-Pascual A.
      • Carmena R.
      • et al.
      Prevalence of diabetes mellitus and impaired glucose regulation in Spain: the diabetes study.
      ,
      • Gardete-Correia L.
      • Boavida J.M.
      • Raposo J.F.
      • Mesquita A.C.
      • Fona C.
      • Carvalho R.
      • et al.
      First diabetes prevalence study in Portugal: PREVADIAB study.
      ,
      • Saaristo T.E.
      • Barengo N.C.
      • Korpi-Hyövälti E.
      • Oksa H.
      • Puolijoki H.
      • Saltevo J.T.
      • et al.
      High prevalence of obesity, central obesity and abnormal glucose tolerance in the middle-aged Finnish population.
      ]. These proportions are comparable to other studies using corresponding methods [
      • van’tRiet E.
      • Alssema M.
      • Rijkelijkhuizen J.M.
      • Kostense P.J.
      • Nijpels G.
      • Dekker J.M.
      Relationship between A1C and glucose levels in the general Dutch population: the new Hoorn study.
      ,
      • Rathmann W.
      • Haastert B.
      • Icks A.
      • Löwel H.
      • Meisinger C.
      • Holle R.
      • et al.
      High prevalence of undiagnosed diabetes mellitus in Southern Germany: target populations for efficient screening: the KORA survey 2000.
      ]. Therefore, undiagnosed diabetes is considered to account for 40–50% of all cases with diabetes in Europe when the gold standard for epidemiologic studies is applied, although this may vary by population.
      The OGTT-based studies also provided estimates on pre-diabetes (including impaired fasting glucose and impaired glucose tolerance) which ranged from 14% in Spain to 30% in Turkey. Since pre-diabetes is an important risk factor for future type 2 diabetes, the high numbers in Turkey suggest that the prevalence of diabetes in this country is not likely to decrease in the near future.

      2.1.3 Regional differences

      For the 2013 edition of the IDF Diabetes Atlas, nationwide population-based data was given priority over regional data. However, it should be noted that, in Europe, considerable regional differences in diabetes prevalence within countries are known to exist, which are important for planning local approaches to prevention and healthcare. For example, in Germany, regions of the former German Democratic Republic consistently have up to a twofold higher standardised prevalence in known type 2 diabetes [
      • Schipf S.
      • Werner A.
      • Tamayo T.
      • Holle R.
      • Schunk M.
      • Maier W.
      • et al.
      Regional differences in the prevalence of known type 2 diabetes mellitus in 45–74 years old individuals: results from six population-based studies in Germany (DIAB-CORE Consortium).
      ], hypertension [
      • Meisinger C.
      • Heier M.
      • Völzke H.
      • Löwel H.
      • Mitusch R.
      • Hense H.W.
      • et al.
      Regional disparities of hypertension prevalence and management within Germany.
      ] and an increased waist circumference [
      • Stang A.
      • Döring A.
      • Völzke H.
      • Moebus S.
      • Greiser K.H.
      • Werdan K.
      • et al.
      Regional differences in body fat distributions among people with comparable body mass index: a comparison across six German population-based surveys.
      ] than in the south [
      • Schipf S.
      • Werner A.
      • Tamayo T.
      • Holle R.
      • Schunk M.
      • Maier W.
      • et al.
      Regional differences in the prevalence of known type 2 diabetes mellitus in 45–74 years old individuals: results from six population-based studies in Germany (DIAB-CORE Consortium).
      ]. Regional differences in the prevalence of type 2 diabetes were also found comparing eastern and south-western Finland as well as the Helsinki-Vaanta region [
      • Ylihärsilä H.
      • Lindström J.
      • Eriksson J.G.
      • Jousilahti P.
      • Valle T.T.
      • Sundvall J.
      • et al.
      Prevalence of diabetes and impaired glucose regulation in 45- to 64-year-old individuals in three areas of Finland.
      ]. Diabetes prevalence also varied between regions in England [
      • Congdon P.
      Estimating diabetes prevalence by small area in England.
      ].
      Structural deprivation may explain part of the regional differences along with individual socioeconomic status or ethnic mixture [
      • Congdon P.
      Estimating diabetes prevalence by small area in England.
      ,
      • Maier W.
      • Holle R.
      • Hunger M.
      • Peters A.
      • Meisinger C.
      • Greiser K.H.
      • et al.
      The Diabetes Collaborative Research of Epidemiologic Studies (DIAB-CORE) consortium. The impact of regional deprivation and individual socio-economic status on the prevalence of Type 2 diabetes in Germany. A pooled analysis of five population-based studies.
      ]. Additionally, national estimates are unlikely to represent diabetes prevalence in ethnic minority populations. For example, Turkish immigrants living in Sweden, type 2 diabetes prevalence was higher among females compared to males (similar to findings from Turkey [
      • Satman I.
      • Omer B.
      • Tutuncu Y.
      • Kalaca S.
      • Gedik S.
      • Dinccag N.
      • et al.
      TURDEP-II Study Group. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults.
      ]) while the opposite pattern was found among the Swedish population. This might be associated with sex differences in obesity prevalence between populations [
      • Carlsson A.C.
      • Wändell P.E.
      • Hedlund E.
      • Walldius G.
      • Nordqvist T.
      • Jungner I.
      • et al.
      Country of birth-specific and gender differences in prevalence of diabetes in Sweden.
      ]. Diabetes prevalence among South Asians was lower in the UK than in the Netherlands, suggesting a modification of diabetes risk by the environment in which minorities live [
      • Angyamang C.
      • Kunst A.E.
      • Bhopal R.
      • Anujuo K.
      • Zaninotto P.
      • Nazroo J.
      • et al.
      Diabetes prevalence in populations of South Asian Indian and African origins: a comparison of England and the Netherlands.
      ]. Although the role of regional differences related to deprivation or ethnicity is a complex issue, this needs to be addressed in future European studies.

      2.2 Childhood onset type 1 diabetes

      2.2.1 Incidence estimates and time trends

      Compared with other regions, EUR has the most informative and reliable data on type 1 diabetes incidence, as many countries maintain incidence registries – either nationwide or covering different parts of the country and using standardised methods.
      The updated estimates of the incidence (20.04 per 100,000 per year) and prevalent cases (129,350) of type 1 diabetes in children 0–14 years old in Europe for 2013 [
      • Patterson C.C.
      • Guariguata L.
      • Dahlquist G.
      • Soltesz G.
      • Ogle G.D.
      • Silink M.
      Diabetes in the young – a global view and worldwide estimates of numbers of children with type 1 diabetes.
      ] reflect an increasing trend of 3–4% per annum during the past 20 years [
      • Patterson C.C.
      • Dahlquist G.G.
      • Gyürüs E.
      • Green A.
      • Soltész G.
      EURODIAB Study Group. Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study.
      ].
      Core data for the European estimates of type 1 diabetes in childhood originate predominantly from the EURODIAB Study Group. All EURODIAB centres operate in geographically defined regions using standardised definitions and at least two independent data sources for registration of new type diabetes cases (completeness >90%) [
      • Patterson C.C.
      • Dahlquist G.G.
      • Gyürüs E.
      • Green A.
      • Soltész G.
      EURODIAB Study Group. Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study.
      ,
      • Patterson C.C.
      • Gyürüs E.
      • Rosenbauer J.
      • Cinek O.
      • Neu A.
      • Schober E.
      • et al.
      Trends in childhood type 1 diabetes incidence in Europe during 1989–2008: evidence of non-uniformity over time in rates of increase.
      ]. Therefore, the estimates can be assumed to be valid, and the observed heterogeneity in the incidence level can be presumed to mirror real patterns, although the extrapolation of estimates from small regions to the whole country might be questionable in some countries due to possible within-country heterogeneity.
      Besides geographic variation in the level of type 1 diabetes incidence, recent data from EURODIAB Study Group indicated a considerable heterogeneity in the increasing incidence over time. The rise in incidence was most marked in low-incidence countries [
      • Patterson C.C.
      • Gyürüs E.
      • Rosenbauer J.
      • Cinek O.
      • Neu A.
      • Schober E.
      • et al.
      Trends in childhood type 1 diabetes incidence in Europe during 1989–2008: evidence of non-uniformity over time in rates of increase.
      ]. Increasing incidence in some European countries was not uniform during the 20 years of observation but showed periods of more or less rapid increase [
      • Patterson C.C.
      • Dahlquist G.G.
      • Gyürüs E.
      • Green A.
      • Soltész G.
      EURODIAB Study Group. Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study.
      ]. Long-term incidence data from Finland, Sweden and the Czech Republic recently showed lower rates of increase in the 1980s and an accelerated increase in the 1990s, to a stabilised trend in the 2000s [
      • Cinek O.
      • Kulich M.
      • Sumnik Z.
      The incidence of type 1 diabetes in young Czech children stopped rising.
      ,
      • Berhan Y.
      • Waernbaum I.
      • Lind T.
      • Möllsten A.
      • Dahlquist G.
      Swedish Childhood Diabetes Study Group. Thirty years of prospective nationwide incidence of childhood type 1 diabetes: the accelerating increase by time tends to level off in Sweden.
      ,
      • Harjutsalo V.
      • Sund R.
      • Knip M.
      • Groop P.H.
      Incidence of type 1 diabetes in Finland.
      ].
      The IDF Diabetes Atlas presents data on type 1 diabetes only for the children under the age of 15 years. Only a few European registers investigated type 1 diabetes rates up to the age of 30 years [
      • Kyvik K.O.
      • Nystrom L.
      • Gorus F.
      • Songini M.
      • Oestman J.
      • Castell C.
      • et al.
      The epidemiology of type 1 diabetes mellitus is not the same in young adults as in children.
      ]. These studies indicated the incidence in older age groups was lower than in the 0–14 year age range and the rate in males was about twice that in females, unlike in the younger age group (0–14 years) in which sex differences were less marked [
      • Dahlquist G.G.
      • Nyström L.
      • Patterson C.C.
      Swedish Childhood Diabetes Study Group; Diabetes Incidence in Sweden Study Group. Incidence of type 1 diabetes in Sweden among individuals aged 0–34 years, 1983–2007: an analysis of time trends.
      ]. Swedish data provides evidence for stationary or declining type 1 diabetes incidence rates in young adults (<35 years), indicating a shift to younger age at onset. However, data from Italy, the UK, and Finland showed an increasing trend in type 1 diabetes incidence also in the age group of young adults [
      • Bruno G.
      • Novelli G.
      • Panero F.
      • Perotto M.
      • Monasterolo F.
      • Bona G.
      • et al.
      Piedmont Study Group for Diabetes Epidemiology. The incidence of type 1 diabetes is increasing in both children and young adults in Northern Italy: 1984–2004 temporal trends.
      ,
      • Imkampe A.K.
      • Gulliford M.C.
      Trends in type 1 diabetes incidence in the UK in 0- to 14-year-olds and in 15- to 34-year-olds, 1991–2008.
      ,
      • Lammi N.
      • Blomstedt P.A.
      • Moltchanova E.
      • Eriksson J.G.
      • Tuomilehto J.
      • Karvonen M.
      Marked temporal increase in the incidence of type 1 and type 2 diabetes among young adults in Finland.
      ]. Studies covering all age groups are still lacking but these are necessary to investigate changes in the cumulative lifetime incidence of type 1 diabetes over time.

      2.2.2 Risk factors

      The incidence rates of type 1 diabetes in European countries were positively associated with country level income [
      • Patterson C.C.
      • Dahlquist G.
      • Soltész G.
      • Green A.
      EURODIAB ACE Study Group. Europe and diabetes is childhood-onset type I diabetes a wealth-related disease? An ecological analysis of European incidence rates.
      ]. However, the drivers for the observed pattern with geographical differences and varying time trends are still unclear. Susceptibility to type 1 diabetes definitely has a strong genetic component (HLA genotype) [
      • Bluestone J.A.
      • Herold K.
      • Eisenbarth G.
      Genetics, pathogenesis and clinical interventions in type 1 diabetes.
      ], but the heterogeneity of type 1 diabetes cannot be explained solely by the prevalence of susceptibility genes [
      • Hermann R.
      • Knip M.
      • Veijola R.
      • Simell O.
      • Laine A.P.
      • Akerblom H.K.
      • et al.
      FinnDiane Study Group. Temporal changes in the frequencies of HLA genotypes in patients with type 1 diabetes-indication of an increased environmental pressure?.
      ,
      • Gillespie K.M.
      • Bain S.C.
      • Barnett A.H.
      • Bingley P.J.
      • Christie M.R.
      • Gill G.V.
      • et al.
      The rising incidence of childhood type 1 diabetes and reduced contribution of high-risk HLA haplotypes.
      ,
      • Fourlanos S.
      • Varney M.D.
      • Tait B.D.
      • Morahan G.
      • Honeyman M.C.
      • Colman P.G.
      • et al.
      The rising incidence of type 1 diabetes is accounted for by cases with lower-risk human leukocyte antigen genotypes.
      ]. Thus, the reasons for changes in the incidence are likely to be attributable to changes in environmental risk factors or lifestyle habits acting differently across European countries – possibly in interplay with genetic factors. Environmental factors and the underlying pathogenetic mechanisms, currently discussed, are listed in Table 1. Some studies suggest that the increasing incidence originates, at least in part, from an accelerated progression from initiation of beta-cell autoimmunity to overt type 1 diabetes, rather than an increase in the prevalence of beta-cell autoimmunity itself [
      • Ziegler A.G.
      • Meier-Stiegen F.
      • Winkler C.
      • Bonifacio E.
      TEENDIAB Study Group. Prospective evaluation of risk factors for the development of islet autoimmunity and type 1 diabetes during puberty-TEENDIAB: study design.
      ].
      Table 1Environmental factors associated with the increase in type 1 diabetes in Europe.
      Adapted from Knip
      • Knip M.
      Descriptive epidemiology of type 1 diabetes-is it still in?.
      .
      Environmental factorsHypothesis and mechanism [source]
      Lifestyle• Overload of the beta cells sensitises them to immune damage
      • Dahlquist G.
      Can we slow the rising incidence of childhood-onset autoimmune diabetes? The overload hypothesis.
      ,
      • Ludvigsson J.
      Why diabetes incidence increases – a unifying theory.
      Foetal and peri-natal factors• Rapid weight gain in childhood
      • Wilkin T.J.
      The accelerator hypothesis: weight gain as the missing link between type I and type II diabetes.
      • Caesarean section
      • Stene L.C.
      • Rønningen K.S.
      • Undlien D.E.
      • Joner G.
      Does the relative risk for type 1 diabetes conferred by HLA-DQ INS, and PTPN22 polymorphisms vary with maternal age, birth weight, or cesarean section?.
      ,
      • Bonifacio E.
      • Warncke K.
      • Winkler C.
      • Wallner M.
      • Ziegler A.G.
      Cesarean section and interferon-induced helicase gene polymorphisms combine to increase childhood type 1 diabetes risk.
      • Breastfeeding, birth order, maternal age, birth weight, viral infections
      • Cardwell C.R.
      • Stene L.C.
      • Ludvigsson J.
      • Rosenbauer J.
      • Cinek O.
      • Svensson J.
      • et al.
      Breast-feeding and childhood-onset type 1 diabetes: a pooled analysis of individual participant data from 43 observational studies.
      ,
      • Patelarou E.
      • Girvalaki C.
      • Brokalaki H.
      • Patelarou A.
      • Androulaki Z.
      • Vardavas C.
      Current evidence on the associations of breastfeeding, infant formula, and cow's milk introduction with type 1 diabetes mellitus: a systematic review.
      ,
      • Cardwell C.R.
      • Stene L.C.
      • Joner G.
      • Bulsara M.K.
      • Cinek O.
      • Rosenbauer J.
      • et al.
      Birth order and childhood type 1 diabetes risk: a pooled analysis of 31 observational studies.
      ,
      • Cardwell C.R.
      • Stene L.C.
      • Joner G.
      • Bulsara M.K.
      • Cinek O.
      • Rosenbauer J.
      • et al.
      Maternal age at birth and childhood type 1 diabetes: a pooled analysis of 30 observational studies.
      ,
      • Cardwell C.R.
      • Stene L.C.
      • Joner G.
      • Davis E.A.
      • Cinek O.
      • Rosenbauer J.
      • et al.
      Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data.
      ,
      • Cardwell C.R.
      • Stene L.C.
      • Joner G.
      • Cinek O.
      • Svensson J.
      • Goldacre M.J.
      • et al.
      Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies.
      ,
      • Yeung W.C.
      • Rawlinson W.D.
      • Craig M.E.
      Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies.
      Dietary factors• Early introduction of complex dietary proteins
      • Hara N.
      • Alkanani A.K.
      • Ir D.
      • Robertson C.E.
      • Wagner B.D.
      • Frank D.N.
      • et al.
      The role of the intestinal microbiota in type 1 diabetes.
      ,
      • Beyan H.
      • Wen L.
      • Leslie R.D.
      Guts, germs, and meals: the origin of type 1 diabetes.
      ,
      • Atkinson M.A.
      • Chervonsky A.
      Does the gut microbiota have a role in type 1 diabetes? Early evidence from humans and animal models of the disease.
      • Vitamin D deficiency
      • Mohr S.B.
      • Garland C.F.
      • Gorham E.D.
      • Garland F.C.
      The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide.
      ,
      • Cooper J.D.
      • Smyth D.J.
      • Walker N.M.
      • Stevens H.
      • Burren O.S.
      • Wallace C.
      • et al.
      Inherited variation in vitamin D genes is associated with predisposition to autoimmune disease type 1 diabetes.
      Exposure to pathogens• Decreased exposure to pathogens
      • Kolb H.
      • Elliott R.B.
      Increasing incidence of IDDM a consequence of improved hygiene?.
      • Enterovirus infections
      • Knip M.
      Descriptive epidemiology of type 1 diabetes-is it still in?.
      • Environmental pollution
      • Howard S.G.
      • Lee D.H.
      What is the role of human contamination by environmental chemicals in the development of type 1 diabetes?.
      ,
      • Howard S.G.
      Comment on: Berhan. Thirty years of prospective nationwide incidence of childhood type 1 diabetes: the accelerating increase by time tends to level off in Sweden.
      So far there is no clear evidence for measures that may prevent type 1 diabetes [
      • Harjutsalo V.
      • Sund R.
      • Knip M.
      • Groop P.H.
      Incidence of type 1 diabetes in Finland.
      ]. Therefore, the major focus for type 1 diabetes should be on diabetes care to support the best possible quality and quantity of life among people with type 1 diabetes.

      3. Morbidity and mortality

      As the global prevalence of diabetes increases so will the number of people with diabetes developing complications. In contrast to the relatively well-documented (global) prevalence of diabetes, much less is known about the epidemiology of diabetes complications. Because diabetic complications are responsible for most of the morbidity and mortality associated with diabetes, there is an urgent need to fill this gap.

      3.1 Diabetic retinopathy

      Diabetic retinopathy is a very frequent microvascular complication with comparatively good quality data available [
      • Prokofyeva E.
      • Zrenner E.
      Epidemiology of major eye diseases leading to blindness in Europe: a literature review.
      ,
      • Ruta L.M.
      • Magliano D.J.
      • Lemesurier R.
      • Taylor H.R.
      • Zimmet P.Z.
      • Shaw J.E.
      Prevalence of diabetic retinopathy in type 2 diabetes in developing and developed countries.
      ,
      • Yau J.W.
      • Rogers S.L.
      • Kawasaki R.
      • Lamoureux E.L.
      • Kowalski J.W.
      • Bek T.
      • et al.
      Global prevalence and major risk factors of diabetic retinopathy.
      ]. The crude prevalence of any diabetic retinopathy in primary care clinic studies in Europe assessed by fund us photography ranged from 25% [
      • Wandell P.E.
      • Gafvels C.
      Patients with type 2 diabetes aged 35–64 years at four primary health care centres in Stockholm County, Sweden. Prevalence and complications in relation to gender and socio-economic status.
      ] to 28% [
      • Santos Bueso E.
      • Fernández-Vigo J.
      • Fernández Pérez C.
      • Macarro Merino A.
      • FernándezPerianes J.
      Prevalence of diabetic retinopathy in the Regional Community of Extremadura 1997–2001 (Extremadura Project to Prevent Blindness).
      ] in patients with known type 2 diabetes. When assessed by medical record review, the range was wider and the prevalence varied from 11% in a French study [
      • Detournay B.
      • Cros S.
      • Charbonnel B.
      • Grimaldi A.
      • Liard F.
      • Cogneau J.
      • et al.
      Managing type 2 diabetes in France: the ECODIA survey.
      ] to nearly 51% in Germany [
      • Happich M.
      • Breitscheidel L.
      • Meisinger C.
      • Ulbig M.
      • Falkenstein P.
      • Benter U.
      • et al.
      Cross-sectional analysis of adult diabetes type 1 and type 2 patients with diabetic microvascular complications from a German retrospective observational study.
      ]. There is a large number of factors affecting the prevalence estimates, predominantly the method used to diagnose diabetic retinopathy [
      • Prokofyeva E.
      • Zrenner E.
      Epidemiology of major eye diseases leading to blindness in Europe: a literature review.
      ]. Therefore, standardisation of the diabetic retinopathy assessment and grading is the first step to increase comparability of prevalence estimates between countries in Europe.

      3.2 Diabetic nephropathy

      Although diabetic nephropathy increases the risk of mortality, European estimates on the prevalence of microalbuminuria and diabetic nephropathy are scarce. Country-specific estimates are difficult to compare because of different assessment methods and different settings and study designs (e.g. [
      • Assogba G.F.
      • Couchoud C.
      • Roudier C.
      • Pornet C.
      • Fosse S.
      • Romon I.
      • et al.
      Prevalence, screening and treatment of chronic kidney disease in people with type 2 diabetes in France: the ENTRED surveys (2001 and 2007).
      ,
      • Rodriguez-Poncelas A.
      • Garre-Olmo J.
      • Franch-Nadal J.
      • Diez-Espino J.
      • Mundet-Tuduri X.
      • Barrot-De la Puente J.
      • et al.
      Prevalence of chronic kidney disease in patients with type 2 diabetes in Spain: PERCEDIME2 study.
      ]). A global primary care study on microalbuminuria estimated the global prevalence of microalbuminuria and macroalbuminuria (measured by dipstick) to be 39% and 10%, respectively, with slightly lower estimates in people of European ancestry [
      • Parving H.H.
      • Lewis J.B.
      • Ravid M.
      • Remuzzi G.
      • Hunsicker L.G.
      Prevalence and risk factors for microalbuminuria in a referred cohort of type II diabetic patients: a global perspective.
      ]. These high estimates have implications for the incidence of end-stage renal disease and the future use of renal replacement therapy [
      • Rossing P.
      Diabetic nephropathy: worldwide epidemic and effects of current treatment on natural history.
      ]. The age- and sex-adjusted prevalence of renal replacement therapy among diabetic patients in Europe in 2011 ranged from about 95 to 220 per million [
      • Registry E.-E.
      ERA-EDTA registry annual report 2011.
      ].

      3.3 Diabetic neuropathy

      A comparison of prevalence of peripheral diabetic neuropathy (PNP) between studies is difficult. Study composition, ethnicity, diagnostic criteria, and source of a particular study population have direct implications for the observed occurrence of PNP [
      • Singh N.
      • Armstrong D.G.
      • Lipsky B.A.
      Preventing foot ulcers in patients with diabetes.
      ].
      The prevalence of PNP in type 2 diabetes varies between 18% and 35% for European study populations [
      • Beghi E.
      • Monticelli M.L.
      Diabetic polyneuropathy in the elderly. Prevalence and risk factors in two geographic areas of Italy Italian General Practitioner Study Group (IGPSG).
      ,
      • Cabezas-Cerrato J.
      The prevalence of clinical diabetic polyneuropathy in Spain: a study in primary care and hospital clinic groups Neuropathy Spanish Study Group of the Spanish Diabetes Society (SDS).
      ,
      • Delcourt C.
      • Vauzelle-Kervroedan F.
      • Cathelineau G.
      • Papoz L.
      Low prevalence of long-term complications in non-insulin-dependent diabetes mellitus in France: a multicenter study. CODIAB-INSERM-ZENECA Pharma Study Group.
      ,
      • Tesfaye S.
      • Stevens L.K.
      • Stephenson J.M.
      • Fuller J.H.
      • Plater M.
      • Ionescu-Tirgoviste C.
      • et al.
      Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM complications study.
      ,
      • Veglio M.
      • Sivieri R.
      Prevalence of neuropathy in IDDM patients in Piemonte, Italy. The Neuropathy Study Group of the Italian Society for the Study of Diabetes, Piemonte Affiliate.
      ,
      • Ziegler D.
      • Gries F.A.
      • Muhlen H.
      • Rathmann W.
      • Spuler M.
      • Lessmann F.
      Prevalence and clinical correlates of cardiovascular autonomic and peripheral diabetic neuropathy in patients attending diabetes centers. The Diacan Multicenter Study Group.
      ,
      • Fedele D.
      • Comi G.
      • Coscelli C.
      • Cucinotta D.
      • Feldman E.L.
      • Ghirlanda G.
      • et al.
      A multicenter study on the prevalence of diabetic neuropathy in Italy Italian Diabetic Neuropathy Committee.
      ,
      • Verhoeven S.
      • van Ballegooie E.
      • Casparie A.F.
      Impact of late complications in type 2 diabetes in a Dutch population.
      ,
      • Kumar S.
      • Ashe H.A.
      • Parnell L.N.
      • Fernando D.J.
      • Tsigos C.
      • Young R.J.
      • et al.
      The prevalence of foot ulceration and its correlates in type 2 diabetic patients: a population-based study.
      ,
      • Walters D.P.
      • Gatling W.
      • Mullee M.A.
      • Hill R.D.
      The prevalence of diabetic distal sensory neuropathy in an English community.
      ]. In general, reported prevalence rates are somewhat higher for hospital-based study populations [
      • Cabezas-Cerrato J.
      The prevalence of clinical diabetic polyneuropathy in Spain: a study in primary care and hospital clinic groups Neuropathy Spanish Study Group of the Spanish Diabetes Society (SDS).
      ,
      • Delcourt C.
      • Vauzelle-Kervroedan F.
      • Cathelineau G.
      • Papoz L.
      Low prevalence of long-term complications in non-insulin-dependent diabetes mellitus in France: a multicenter study. CODIAB-INSERM-ZENECA Pharma Study Group.
      ,
      • Tesfaye S.
      • Stevens L.K.
      • Stephenson J.M.
      • Fuller J.H.
      • Plater M.
      • Ionescu-Tirgoviste C.
      • et al.
      Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM complications study.
      ,
      • Ziegler D.
      • Gries F.A.
      • Muhlen H.
      • Rathmann W.
      • Spuler M.
      • Lessmann F.
      Prevalence and clinical correlates of cardiovascular autonomic and peripheral diabetic neuropathy in patients attending diabetes centers. The Diacan Multicenter Study Group.
      ] than for primary care or population-based samples [
      • Beghi E.
      • Monticelli M.L.
      Diabetic polyneuropathy in the elderly. Prevalence and risk factors in two geographic areas of Italy Italian General Practitioner Study Group (IGPSG).
      ,
      • Verhoeven S.
      • van Ballegooie E.
      • Casparie A.F.
      Impact of late complications in type 2 diabetes in a Dutch population.
      ,
      • Kumar S.
      • Ashe H.A.
      • Parnell L.N.
      • Fernando D.J.
      • Tsigos C.
      • Young R.J.
      • et al.
      The prevalence of foot ulceration and its correlates in type 2 diabetic patients: a population-based study.
      ]. There is much less data on the occurrence of polyneuropathy in patients with undiagnosed diabetes screened by OGTT on population-level [
      • Herman W.H.
      • Aubert R.E.
      • Engelgau M.M.
      • Thompson T.J.
      • Ali M.A.
      • Sous E.S.
      • et al.
      Diabetes mellitus in Egypt: glycaemic control and microvascular and neuropathic complications.
      ,
      • Rith-Najarian S.J.
      • Stolusky T.
      • Gohdes D.M.
      Identifying diabetic patients at high risk for lower-extremity amputation in a primary health care setting. A prospective evaluation of simple screening criteria.
      ,
      • Shaw J.E.
      • Hodge A.M.
      • de Courten M.
      • Dowse G.K.
      • Gareeboo H.
      • Tuomilehto J.
      • et al.
      Diabetic neuropathy in Mauritius: prevalence and risk factors.
      ]. In these studies, prevalence rates of polyneuropathy in individuals with undiagnosed diabetes were found to range between 4% and 19% [
      • Bongaerts B.W.
      • Rathmann W.
      • Kowall B.
      • Herder C.
      • Stöckl D.
      • Meisinger C.
      • et al.
      Postchallenge hyperglycemia is positively associated with diabetic polyneuropathy: the KORA F4 study.
      ]. In one survey in Southern Germany, among subjects with known diabetes who reported to have had their feet examined by a physician, 72% subjects with PNP were unaware of having the disorder, suggesting inadequate attention to diabetic foot syndrome prevention [
      • Bongaerts B.W.
      • Rathmann W.
      • Heier M.
      • Kowall B.
      • Herder C.
      • Stöckl D.
      • et al.
      Older subjects with diabetes and prediabetes are frequently unaware of having distal sensorimotor polyneuropathy: the KORA F4 study.
      ].

      3.4 Cardiovascular disease in diabetes

      There are very few recent studies on the prevalence of cardiovascular disease (CVD) in diabetic patients in European countries [
      • Ringborg A.
      • Lindgren P.
      • Martinell M.
      • Yin D.D.
      • Schon S.
      • Stalhammar J.
      Prevalence and incidence of type 2 diabetes and its complications 1996–2003 – estimates from a Swedish population-based study.
      ]. There is marked heterogeneity of incidence studies in terms of duration of follow-up, assessment of cardiovascular events [
      • Almdal T.
      • Scharling H.
      • Jensen J.S.
      • Vestergaard H.
      The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up.
      ,
      • Schramm T.K.
      • Gislason G.H.
      • Kober L.
      • Rasmussen S.
      • Rasmussen J.N.
      • Abildstrom S.Z.
      • et al.
      Diabetes patients requiring glucose-lowering therapy and nondiabetics with a prior myocardial infarction carry the same cardiovascular risk: a population study of 3.3 million people.
      ,
      • Giorda C.B.
      • Avogaro A.
      • Maggini M.
      • Lombardo F.
      • Mannucci E.
      • Turco S.
      • et al.
      Incidence and risk factors for stroke in type 2 diabetic patients: the DAI study.
      ] and setting such as hospital- or population-based [
      • Ringborg A.
      • Lindgren P.
      • Martinell M.
      • Yin D.D.
      • Schon S.
      • Stalhammar J.
      Prevalence and incidence of type 2 diabetes and its complications 1996–2003 – estimates from a Swedish population-based study.
      ,
      • Almdal T.
      • Scharling H.
      • Jensen J.S.
      • Vestergaard H.
      The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up.
      ,
      • Giorda C.B.
      • Avogaro A.
      • Maggini M.
      • Lombardo F.
      • Mannucci E.
      • Turco S.
      • et al.
      Incidence and risk factors for stroke in type 2 diabetic patients: the DAI study.
      ,
      • Avogaro A.
      • Giorda C.
      • Maggini M.
      • Mannucci E.
      • Raschetti R.
      • Lombardo F.
      • et al.
      Incidence of coronary heart disease in type 2 diabetic men and women: impact of microvascular complications, treatment, and geographic location.
      ]. Because of this paucity and heterogeneity of data it is not possible to quantify the prevalence and incidence of CVD in patients with diabetes in Europe.

      3.5 Disability and quality of life

      The evidence for the relation between diabetes and physical and functional disability is currently being reviewed [
      • Wong E.
      • Backholer K.
      • Harding J.
      • Gearon E.
      • Stevenson C.
      • Freak-Poli R.
      • et al.
      A systematic review and meta-analysis of diabetes and risk of physical disability and functional impairment – protocol.
      ]. In general, diabetes and diabetes complications negatively affect quality of life [
      • Schunk M.
      • Reitmeir P.
      • Schipf S.
      • VölzkeH
      • Meisinger C.
      • Thorand B.
      • et al.
      Health-related quality of life in subjects with and without type 2 diabetes: pooled analysis of five population-based surveys in Germany.
      ]. There is also evidence that interventions, be they educational, pharmaceutical or surgical, have a positive impact on quality of life of diabetes patients [
      • Zhang X.
      • Norris S.L.
      • Chowdhury F.M.
      • Gregg E.W.
      • Zhang P.
      The effects of interventions on health-related quality of life among persons with diabetes: a systematic review.
      ]. Condition-specific instruments to measure the impact of diabetes complications on health related quality of life may be better than generic instruments [
      • Fenwick E.K.
      • Xie J.
      • Ratcliffe J.
      • Pesudovs K.
      • Finger R.P.
      • Wong T.Y.
      • et al.
      The impact of diabetic retinopathy and diabetic macular edema on health-related quality of life in type 1 and type 2 diabetes.
      ].

      3.6 Mortality

      In Europe, as for other regions such as North America [
      • Gregg E.W.
      • Cheng Y.J.
      • Saydah S.
      • Cowie C.
      • Garfield S.
      • Geiss L.
      • et al.
      Trends in death rates among U.S. adults with and without diabetes between 1997 and 2006: findings from the National Health Interview Survey.
      ], a decline in the diabetes-related mortality has been observed in recent years. In Iceland, CVD-related mortality in persons with type 2 diabetes was compared between two cohorts ten years apart, and CVD-mortality in persons with type 2 diabetes declined by 32% and all-cause mortality rate by 19%[
      • Olafsdottir E.
      • Aspelund T.
      • Sigurdsson G.
      • Benediktsson R.
      • Thorsson B.
      • Harris T.B.
      • et al.
      Similar decline in mortality rate of older persons with and without type 2 diabetes between 1993 and 2004 the Icelandic population-based Reykjavik and AGES-Reykjavik cohort studies.
      ]. Similarly, mortality rates declined from 117 to 46 per 1000 persons during the 8-year follow-up of a British study [
      • Nwaneri C.
      • Bowen-Jones D.
      • Cooper H.
      • Chikkaveerappa K.
      • Afolabi B.A.
      Falling mortality rates in type 2 diabetes mellitus in the Wirral Peninsula: a longitudinal and retrospective cohort population-based study.
      ,
      • Gulliford M.C.
      • Charlton J.
      Is relative mortality of type 2 diabetes mellitus decreasing?.
      ]. However, in comparison to the UK general population, people with type 2 diabetes still had a reduced life expectancy (6–8 years reduction in persons diagnosed at age 50) [
      • Nwaneri C.
      • Bowen-Jones D.
      • Cooper H.
      • Chikkaveerappa K.
      • Afolabi B.A.
      Falling mortality rates in type 2 diabetes mellitus in the Wirral Peninsula: a longitudinal and retrospective cohort population-based study.
      ]. It is of particular concern that an increased mortality seems to be prevalent already in undiagnosed diabetes [
      • Kowall B.
      • Rathmann W.
      • Heier M.
      • Giani G.
      • Peters A.
      • Thorand B.
      • et al.
      Categories of glucose tolerance and continuous glycemic measures and mortality.
      ].
      CVD mortality also decreased substantially during the last 10 years in people with type 1 diabetes [
      • Livingstone S.J.
      • Looker H.C.
      • Hothersall E.J.
      • Wild S.H.
      • Lindsay R.S.
      • Chalmers J.
      • et al.
      Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish registry linkage study.
      ,
      • Jørgensen M.E.
      • Almdal T.P.
      • Carstensen B.
      Time trends in mortality rates in type 1 diabetes from 2002 to 2011.
      ], likely due to improvements in care. For example, mean survival time of patients starting renal replacement therapy in Finland has progressively increased since 1980 [
      • Haapio M.
      • Helve J.
      • Groop P.H.
      • Grönhagen-Riska C.
      • Finne P.
      Survival of patients with type 1 diabetes receiving renal replacement therapy in 1980–2007.
      ]. However, in a Finnish study the positive trend only applied for individuals with diabetes onset between age 0 and 14 years [
      • Harjutsalo V.
      • Forsblom C.
      • Groop P.H.
      Time trends in mortality in patients with type 1 diabetes: nationwide population based cohort study.
      ].

      3.7 Mortality and socioeconomic status

      In a different Finnish study based on death records, diabetes-related mortality also declined between 1997 and 2006 in all socioeconomic groups [
      • Manderbacka K.
      • Peltonen R.
      • Koskinen S.
      • Martikainen P.
      The burden of diabetes mortality in Finland 1988–2007 – a brief report.
      ]. Mortality was substantially higher in farmers and manual workers than in non-manual workers and lowest in upper non-manual workers. Disparities in mortality have also been found for different levels of area-based social deprivation in Scotland [
      • Walker J.J.
      • Livingstone S.J.
      • Colhoun H.M.
      • Lindsay R.S.
      • McKnight J.A.
      • Morris A.D.
      • et al.
      Scottish Diabetes Research Network Epidemiology Group. Effect of socioeconomic status on mortality among people with type 2 diabetes: a study from the Scottish Diabetes Research Network Epidemiology Group.
      ].

      3.8 Death certificates

      Many epidemiological studies rely on mortality registries. Though, death certificates tend to underestimate diabetes prevalence and falsely estimate the numbers of diabetes-related deaths. Besides, certificates, selection and coding rules and their presentation vary between countries and publications. Standardised completion of death certificates and standardised reports on diabetes related mortality stemming from mortality registries are required [
      • Rao Ch.
      • Doi S.A.R.
      Measuring population-based diabetes-related mortality: a summary of requirements.
      ].

      4. Determinants of health: risk factors and social environments

      Type 2 diabetes is a result of the interplay between lifestyle, environmental and genetic factors. This section focuses on understanding the association between risk factors and diabetes, as well as understanding their distribution and trends in EUR.

      4.1 Established risk factors

      Overweight and obesity and increasing age form the most potent risk factors for type 2 diabetes. According to the WHO, obesity prevalence has tripled over the past two decades, with one in five Europeans being obese (BMI ≥30 kg/m2) and 25–70% being overweight (BMI ≥25 kg/m2) in 2010. Overall, there is a threefold variation in obesity prevalence among European countries, from around 8% in Romania and Switzerland to over 25% in Hungary and the UK [
      • OECD
      Health at a glance: Europe 2012.
      ].
      Clinical trials of the primary prevention of type 2 diabetes have demonstrated that diet and physical activity are important modifiable risk factors for diabetes [
      • Gillies C.L.
      • Abrams K.R.
      • Lambert P.C.
      • Cooper N.J.
      • Sutton A.J.
      • Hsu R.T.
      • et al.
      Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis.
      ]. In the InterAct study, a one-category difference in physical activity was independently associated with a 13% relative reduction in the risk of diabetes [
      • InterAct Consortium
      • Langenberg C.
      • Sharp S.
      • Forouhi N.G.
      • Franks P.W.
      • Schulze M.B.
      • et al.
      Design and cohort description of the InterAct Project: an examination of the interaction of genetic and lifestyle factors on the incidence of type 2 diabetes in the EPIC study.
      ,
      • InterAct consortium
      Physical activity reduces the risk of incident type 2 diabetes in general and in abdominally lean and obese men and women: the EPIC-InterAct study.
      ]. The Eurobarometer survey highlighted that 34% of EU citizens reported being never or only seldom physically active [
      • TNS Opinion & Social
      Special Eurobarometer 334 (Wave 72.3): sport and physical activity.
      ]. The surveys document, that respondents in the Nordic countries and the Netherlands tend to be the most physically active, while those in southern European countries and new Member States are generally the most inactive [
      • TNS Opinion & Social
      Special Eurobarometer 334 (Wave 72.3): sport and physical activity.
      ]. The low levels of physical activity in Europe provide an opportunity to intervene in order to prevent diabetes. Thus efforts to understand the determinants of physical activity behaviour need to be intensified. The use of objective measurement of physical activity and validated instruments are further important priorities to monitor trends.
      InterAct has also provided recent insights on diet and diabetes across Europe (Table 2). The distribution of dietary intake in Europe is difficult to assess, but it is clear that intake varies considerably. From Health-at-a-Glance surveys, the percentage of adults who reported consuming fruit daily varied from 45% in Bulgaria and Romania, to 75% in Italy, Malta and Slovenia, and 84% in Switzerland [
      • OECD
      Health at a glance: Europe 2012.
      ]. Daily vegetable consumption ranged from around 50% in Estonia, Germany, Malta and the Slovak Republic to 75% in France and Slovenia, with Belgium and Ireland highest at 85% and 95%, respectively [
      • OECD
      Health at a glance: Europe 2012.
      ].
      Table 2Key findings from the InterAct study
      Further information about the InterAct project can be found at www.inter-act.eu. There are also other forthcoming publications on dietary factors and the risk of diabetes.
      on the association between dietary factors and the risk of future type 2 diabetes.
      Risk of developing type 2 diabetesDietary factors [source]
      Reduced riskMediterranean diet pattern
      • InterAct Consortium
      • Romaguera D.
      • Guevara M.
      • Norat T.
      • Langenberg C.
      • Forouhi N.G.
      • et al.
      Mediterranean diet and type 2 diabetes risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study: the InterAct project.
      Fruit and vegetable intake
      • Cooper A.J.
      • Forouhi N.G.
      • Ye Z.
      • Buijsse B.
      • Arriola L.
      • Balkau B.
      • et al.
      Fruit and vegetable intake and type 2 diabetes: EPIC-InterAct prospective study and meta-analysis.
      Fermented dairy products
      • Sluijs I.
      • Forouhi N.G.
      • Beulens J.W.
      • van der Schouw Y.T.
      • Agnoli C.
      • Arriola L.
      • et al.
      On behalf of the InterAct Consortium. The amount and type of dairy product intake and incident type 2 diabetes: results from the EPIC-InterAct study.
      Fatty fish intake
      • Patel P.S.
      • Forouhi N.G.
      • Kuijsten A.
      • et al.
      The prospective association between total and type of fish intake and type 2 diabetes in 8 European countries: EPIC-InterAct study.
      Tea intake
      • InterAct Consortium
      Tea consumption and incidence of type 2 diabetes in Europe: the EPIC-InterAct case-cohort study.
      Elevated riskRed and processed meat intake
      • InterAct Consortium
      Association between dietary meat consumption and incident type 2 diabetes: the EPIC-InterAct study.
      Sweetened beverages
      • InterAct Consortium
      Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct.
      Null associationTotal dairy products or milk intake
      • Sluijs I.
      • Forouhi N.G.
      • Beulens J.W.
      • van der Schouw Y.T.
      • Agnoli C.
      • Arriola L.
      • et al.
      On behalf of the InterAct Consortium. The amount and type of dairy product intake and incident type 2 diabetes: results from the EPIC-InterAct study.
      Total fish intake
      • Patel P.S.
      • Forouhi N.G.
      • Kuijsten A.
      • et al.
      The prospective association between total and type of fish intake and type 2 diabetes in 8 European countries: EPIC-InterAct study.
      Dietary energy density
      • InterAct Consortium
      The association between dietary energy density and type 2 diabetes in Europe: results from the EPIC-InterAct study.
      Carbohydrate intake
      • Sluijs I.
      • Beulens J.W.
      • van der Schouw Y.T.
      • van der A.D.L.
      • Buckland G.
      • Kuijsten A.
      • et al.
      Dietaryglycemic index, glycemic load, and digestible carbohydrate intake are not associated with risk of type 2 diabetes in eight European countries.
      a Further information about the InterAct project can be found at www.inter-act.eu. There are also other forthcoming publications on dietary factors and the risk of diabetes.
      In addition to lifestyle factors, it is known that type 2 diabetes has a strong genetic component. Recent genome-wide association studies have identified >60 genetic variants that are associated with type 2 diabetes but individual effects of genetic variants are considered to be small [
      • Morris A.P.
      • Voight B.F.
      • Teslovich T.M.
      • Ferreira T.
      • Segrè A.V.
      • Steinthorsdottir V.
      • et al.
      Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes.
      ,
      • Herder C.
      • Kowall B.
      • Tabak A.G.
      • Rathmann W.
      The potential of novel biomarkers to improve risk prediction of type 2 diabetes.
      ].

      4.2 Emerging risk factors

      There is accumulating evidence that smoking behaviour and psychosocial factors, as well as exposure to environmental pollutants, and biomarkers of metabolic pathways may contribute to developing type 2 diabetes.
      Active smoking is a documented risk factor for type 2 diabetes [
      • Willi C.
      • Bodenmann P.
      • Ghali W.A.
      • Faris P.D.
      • Cornuz J.
      Active smoking and the risk of type 2 diabetes: a systematic review and meta-analysis.
      ]. Overall, the proportion of daily smokers among the adult population varies greatly across European countries [
      • OECD
      Health at a glance: Europe 2012.
      ] but smoking rates have declined on average by about 5 percentage points since 2000. Besides active smoking, several cohort studies also found an increased diabetes incidence among passive smokers [
      • Wang Y.
      • Ji J.
      • Liu Y.J.
      • Deng X.
      • He Q.Q.
      Passive smoking and risk of type 2 diabetes: a meta-analysis of prospective cohort studies.
      ]. Finally, in-utero exposure to maternal smoking is associated with overweight and obesity which may predispose to diabetes and other metabolic disturbances in the offspring [
      • Behl M.
      • Rao D.
      • Aagaard K.
      • Davidson T.L.
      • Levin E.D.
      • Slotkin T.A.
      • et al.
      Evaluation of the association between maternal smoking, childhood obesity, and metabolic disorders: a national toxicology program workshop review.
      ].
      Psychosocial factors encompass two broad areas which are more closely related to socioeconomic status or to psychological/psychiatric factors. Within the InterAct study, people who had a lower educational level had a 70% higher relative risk for diabetes, which remained at around 40% even after adjustment for differences in obesity [
      • Sacerdote C.
      • Ricceri F.
      • Rolandsson O.
      • Baldi I.
      • Chirlaque M.D.
      • Feskens E.
      • et al.
      Lower educational level is a predictor of incident type 2 diabetes in European countries: the EPIC-InterAct study.
      ]. The association between emotional stress, job strain, anxiety and depressive disorders and increased incidence of type 2 diabetes is less well-established, but recent data [
      • Pouwer F.
      • Kupper N.
      • Adriaanse M.C.
      Does emotional stress cause type 2 diabetes mellitus? A review from the European Depression in Diabetes (EDID) Research Consortium.
      ,
      • Fransson E.I.
      • Heikkilä K.
      • Nyberg S.T.
      • Zins M.
      • Westerlund H.
      • Westerholm P.
      • et al.
      Job strain as a risk factor for leisure-time physical inactivity: an individual-participant meta-analysis of up to 170,000 men and women: the IPD-Work Consortium.
      ,
      • Rotella F.
      • Mannucci E.
      Depression as a risk factor for diabetes: a meta-analysis of longitudinal studies.
      ] strongly indicate that this area merits further study to better understand the relationship between these potential risk factors.
      Prospective studies observed that exposure to components of traffic and industry-related air pollution such as nitrogen oxides (e.g. NO2) and fine particulate matter increase the risk of type 2 diabetes [
      • Rajagopalan S.
      • Brook R.D.
      Air pollution and type 2 diabetes: mechanistic insights.
      ]. Air quality has improved in many countries throughout Europe during the last decade, although regional variations are considerable [
      • Richardson E.A.
      • Pearce J.
      • Tunstall H.
      • Mitchell R.
      • Shortt N.K.
      Particulate air pollution and health inequalities: a Europe-wide ecological analysis.
      ], and air pollution lies below levels often found in cities of developing countries [
      • Rajagopalan S.
      • Brook R.D.
      Air pollution and type 2 diabetes: mechanistic insights.
      ]. However, the risk association is apparently linear and not dependent on a threshold effect, thus the widespread exposure to air pollutants remains a metabolic risk factor. Also, man-made persistent organic pollutants showed consistent associations with type 2 diabetes [
      • Taylor K.W.
      • Novak R.F.
      • Anderson H.A.
      • Birnbaum L.S.
      • Blystone C.
      • Devito M.
      • et al.
      Evaluation of the association between persistent organic pollutants (POPs) and diabetes in epidemiological studies: a national toxicology program workshop review.
      ], but the possibility of residual confounding, for example by social inequalities, needs addressing.
      Finally, there is evidence that a range of biomarkers of metabolic pathways including markers of subclinical inflammation, oxidative stress, endothelial and renal dysfunction, adipose-tissue derived hormones, liver enzymes, proteins in blood-coagulation and in tissue damage/remodelling, vitamin D and iron metabolism may be aetiologically related to developing type 2 diabetes [
      • Sattar N.
      • Wannamethee S.G.
      • Forouhi N.G.
      Novel biochemical risk factors for type 2 diabetes: pathogenic insights or prediction possibilities?.
      ,
      • Herder C.
      • Karakas M.
      • Koenig W.
      Biomarkers for the prediction of type 2 diabetes and cardiovascular disease.
      ].
      In conclusion, there is considerable variation across Europe with respect to the prevalence of established and emerging risk factors for diabetes. Overall, the burden of many risk factors seems stable or declining, although increasing age of both native and migrant populations and the long-term exposure to obesity are likely to contribute to a significant increase in the burden of type 2 diabetes in EUR.

      5. Care and management

      Management of chronic diseases, including diabetes, provides a major challenge to health services across Europe as a consequence of increasing prevalence, multi-morbidity and lack of co-ordination between different components and professional groups within health systems. The St. Vincent Declaration provided a set of goals for diabetes care in Europe in 1989 [
      The Saint Vincent Declaration on diabetes care and research in Europe.
      ] and a review 20 years later suggested that, although some progress had been made, considerable gaps remained [
      • Felton A.-M.
      • Hall M.S.
      Diabetes – from St. Vincent to Glasgow. Have we progressed in 20 years?.
      ]. A 2009 review [
      • Scheller-Kreinsen D.
      • Blumel M.
      • Busse R.
      Chronic disease management in Europe.
      ] identified the following approaches that different European countries were taking to address the burden of chronic diseases:
      • 1.
        disease prevention and early detection (although the authors pointed out that prevention “plays only a secondary role in European health systems”),
      • 2.
        new professions, qualifications and settings including nurse-led clinics and presence of secondary-care physicians at community-based clinics,
      • 3.
        disease management programmes based on co-ordinated, evidence-based care, and
      • 4.
        integrated care models that attempt to combine treatment for multiple morbidities rather than having a single disease focus and to co-ordinate care between community, out-patient/ambulatory and in-patient settings.
      The complexity of integrated care models makes meaningful evaluation particularly difficult [
      • Elissen A.M.J.
      • Steuten L.G.M.
      • Lemmens L.C.
      • Drewes H.W.
      • Lemmens K.M.M.
      • Baan C.A.
      • et al.
      Meta-analysis of the effectiveness of chronic care management for diabetes: investigating heterogeneity in outcomes.
      ]. Encouraging self-management of diabetes appears to be challenging in all settings and the roles of blood glucose monitoring for people who are not treated with insulin [
      • Clar C.
      • Barnard K.
      • Cummins E.
      • Royle P.
      • Waugh N.
      Aberdeen Health Technology Assessment Group. Self-monitoring of blood glucose in type 2 diabetes: systematic review.
      ] and of tele-healthcare/remote monitoring [
      • Polisena J.
      • Tran K.
      • Cimon K.
      • Hutton B.
      • McGill S.
      • Palmer K.
      Home telehealth for diabetes management: a systematic review and meta-analysis.
      ] remain controversial.
      Some countries use financial incentives to motivate healthcare providers to meet certain quality standards for structures or processes of care, with the assumption that meeting such standards will improve outcomes. In the UK, where a pay-for-performance scheme, the Quality and Outcome Framework, provides approximately 25% of general practices’ income, the scheme appears to have resulted in more systematic care and has reduced some healthcare inequalities, possibly at the expense of less effective treatments for conditions that are not part of the scheme [
      • Campbell S.
      • Reeves D.
      • Kontopantelis E.
      Quality of primary care in England with the introduction of pay for performance.
      ]. Such schemes are only likely to be feasible in health systems that support continuity of care. For example, since 2007, the Dutch minister of health introduced a bundled-payment approach for integrated diabetes care [
      • Struijs J.N.
      • Baan C.A.
      Integrating care through bundled payments – lessons from the Netherlands.
      ].

      5.1 Barriers to care and access

      Four main barriers (and facilitators) to effective care have been identified [
      • Raaijmakers L.G.M.
      • Hamers F.J.M.
      • Martens M.K.
      • Bagchus C.
      • de Vries N.K.
      • Kremers S.P.J.
      Perceived facilitators and barriers in diabetes care: a qualitative study among health care professionals in the Netherlands.
      ]:
      • 1.
        the patient (for example, lack of knowledge, motivation to change behaviour or to adhere to proposed lifestyle or pharmaceutical interventions),
      • 2.
        the individual professional (for example lack of motivation, effective communication skills knowledge of guidelines or locally available interventions),
      • 3.
        the health care team (for example, lack of communication between different members of a health care team), and
      • 4.
        the organisation of health care (for example, lack of disease registers, individual care plans or financial incentives and lack of guidelines relevant to sub-populations such as the elderly or ethnic minorities).
      Communication between primary and secondary care can be improved using information technology such as the Scottish Care Information diabetes system which provides an electronic patient record of variables related to diabetes care [
      • Cunningham S.
      • McAlpine R.
      • Leese G.
      • Brennan G.
      • Sullivan F.
      • Connacher A.
      • et al.
      Using web technology to support population-based diabetes care.
      ]. In collaboration with partners from other countries, this system has been developed further to allow comparison of outcomes between countries as part of the EUropean Best Information through Regional Outcomes in Diabetes (EUBIROD) project (http://www.eubirod.eu/) which has also highlighted major differences in approaches to data protection between countries [
      • Di Iorio C.T.
      • Carinci F.
      • Brillante M.
      • Azzopardi J.
      • Beck P.
      • Bratina N.
      • et al.
      Cross-border flow of health information: is ‘privacy by design’ enough? Privacy performance assessment in EUBIROD.
      ].

      5.2 Management

      The management of co-morbid conditions among people with diabetes is becoming increasingly important as a consequence of increasing prevalence of multi-morbidity. However, guidelines for managing diabetes are frequently based on findings of randomised controlled trials in which people with co-morbidities are under-represented [
      • Saunders C.
      • Byrne C.D.
      • Guthrie B.
      • Lindsay R.S.
      • McKnight J.A.
      • Philip S.
      • et al.
      External validity of randomized controlled trials of glycaemic control and vascular disease: how representative are participants?.
      ] and therefore may not be appropriate for all patients. As a consequence, clinical judgement is required in identifying treatment targets that are suitable for individual patients including the management of multi-morbidity [
      • Paschou S.A.
      • Leslie R.D.
      Personalizing guidelines for diabetes management: twilight or dawn of the expert?.
      ,
      • Hughes L.D.
      • McMurdo M.E.
      • Guthrie B.
      Guidelines for people not for diseases: the challenges of applying UK clinical guidelines to people with multimorbidity.
      ]. Initiatives such as case management are a possible approach to counteract the fragmented care for patients with multiple diseases. Such programmes attempt to combine various evidence-based treatment protocols and to co-ordinate care with tailoring to individual patients’ preferences.

      5.3 Costs

      Estimating the costs of diabetes to individuals and society is difficult, but estimates suggest that diabetes was responsible for 10% of total health expenditure in Europe for 2010 [
      • Zhang P.
      • Zhang X.
      • Brown J.
      • Vistisen D.
      • Sicree R.
      • Shaw J.
      • et al.
      Global healthcare expenditure on diabetes for 2010 and 2030.
      ]. Regional data from Scotland estimated that 12% of in-patient expenditure in 2005–2007 was diabetes-related [
      • Govan L.
      • Wu O.
      • Briggs A.
      • Colhoun H.M.
      • McKnight J.A.
      • Morris A.D.
      • et al.
      Scottish Diabetes Research Network Epidemiology Group. Inpatient costs for people with type 1 and type 2 diabetes in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group.
      ]. The limited available data suggests that the largest components of costs to health services are the management of complications (even though these costs are likely to be under-estimated) and prescribed drugs. Although prevention of diabetes is likely to be cost-effective, rolling out programmes that have been found to be effective in trial settings for use in normal clinical practice has not been widely achieved. Furthermore, although it is widely believed that disease management programmes reduce health expenditure, a recent review showed that evidence for this claim remains inconclusive [
      • de Bruin S.R.
      • Heijink R.
      • Lemmens L.C.
      • Struijs J.N.
      • Baan C.A.
      Impact of disease management programs on healthcare expenditures for patients with diabetes, depression, heart failure or chronic obstructive pulmonary disease: a systematic review of the literature.
      ]. Nevertheless, disease management programmes are increasingly implemented in health systems worldwide. To support evidence-based decision-making in this field, well-designed economic evaluations are required. In addition, it would be helpful to compare the cost-effectiveness of various approaches to secondary and tertiary prevention of diabetes across countries in order to inform best practice in comparable countries.
      In conclusion, conventional models of care for chronic diseases are not sustainable given increasing prevalence of diabetes and multi-morbidity in Europe and constraints on resources. Over the coming decades, it is essential that cost-effective approaches are developed to managing care differently including greater emphasis on self-management, novel care-delivery mechanisms and integrated care for people with multi-morbidity.

      6. Conclusion

      There is a wide variation of diabetes prevalence in EUR. Age, obesity, physical activity, nutrition, and genetic predisposition all influence diabetes prevalence. There are large differences in distribution of these risk factors at the population level in the Europe Region. The effect of these lifestyle factors on risk of diabetes and how they interact with each other and with genetic factors may also differ in various populations. Furthermore, regional differences in prevalence have been related to socioeconomic deprivation which needs to be considered in future studies. Finally, there is growing evidence that smoking behaviour (including secondhand smoking) and psychosocial factors as well as exposure to environmental pollutants contribute to diabetes development. In light of the growing prevalence of diabetes and environmental pollution these modifiable risk factors could be tackled to reduce incidence of type 2 diabetes in Europe.
      Although micro- and macrovascular disorders are responsible for most of the morbidity and mortality associated with diabetes, there is a lack of good quality epidemiological studies on diabetic complications and on diabetes-related mortality in Europe. Diabetes management is a major challenge to health care services in the European countries. There is often a lack of co-ordination between different components and professional groups within health systems. Improved networking practices of health professionals and other stakeholders in combination with empowerment of people with diabetes and continuous quality monitoring needs to be further developed in Europe.

      Conflicts of Interest

      The authors declare that they have no conflict of interest.

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