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Prevalence of type 2 diabetes mellitus (T2DM) in the adult Russian population (NATION study)
diabetes research and clinical practice 115 (2016) 90–95
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Diabetes Research and Clinical Practice jou rnal hom ep ag e: w ww.e l s e v i er . c om/ loca te / d i ab r es
Prevalence of type 2 diabetes mellitus (T2DM) in the adult Russian population (NATION study) Ivan Dedov a, Marina Shestakova a,b, Massimo Massi Benedetti c, Dominique Simon d, Iakov Pakhomov e,1, Gagik Galstyan a,b,* a
Endocrinology Research Centre, Moscow, Russia I.M. Sechenov First Moscow State Medical University, Moscow, Russia c Hub for International Health Research (HIRS), Perugia, Italy d Diabetes Department and Institute of Cardiometabolism and Metabolism (ICAN), Pitie´-Salpe´trie`re Hospital, Paris, France e Sanofi-Aventis Russia, Moscow, Russia b
article info
abstract
Article history:
Aim: To estimate type 2 diabetes mellitus (T2DM) prevalence in Russian adults.
Received 22 December 2015
Methods: NATION is a national, epidemiological, cross-sectional study, conducted in Russia.
Accepted 24 February 2016
In adults (aged 20–79 years), recruitment was stratified by age, sex, geographic region and
Available online 2 March 2016
settlement type to obtain a representative sample. Recruitment was in public areas with high numbers of people. T2DM was diagnosed by glycated haemoglobin A1c (HbA1c) levels
Keywords:
(diabetes: HbA1c 6.5% [48 mmol/mol]; pre-diabetes: HbA1c 5.7 to <6.5% [39 to
Diabetes mellitus, type 2
<48 mmol/mol]). Socio-demographic and anthropometric data were collected.
Epidemiological study
Results: Blood samples from 26,620 subjects were available. Overall, 5.4% were diagnosed
Undiagnosed diabetes mellitus
with T2DM (previously diagnosed: 2.5%; previously undiagnosed: 2.9%); 19.3% were pre-
Prevalence
diabetic. T2DM prevalence increased with age (up to 70 years) and was higher among
Russia
females than males (6.1% vs. 4.7%, p < 0.001). The estimated proportion of subjects with prediabetes and T2DM tended to increase with increasing body mass index. T2DM prevalence was higher in rural versus urban populations (6.7% vs. 5.0%, p < 0.001). Conclusion: In the Russian adult population, 19.3% had pre-diabetes, T2DM prevalence was 5.4%, and 54% of subjects with diabetes were previously undiagnosed. These results may help to develop a new T2DM predictive, preventative and management programme in Russia. # 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1.
Introduction
Prevalence of diabetes mellitus (DM) is growing worldwide and has reached epidemic proportions in many developing and most developed countries [1,2]. A recent report noted an
estimated prevalence of diabetes of 9.2% (uncertainty interval 4.7–13.3%) for the adult population aged 20–79 years in Russia [2]. According to this estimated prevalence, in Russia, 12.1 million (uncertainty interval 6.2–17.0 million) people aged 20–79 years old are thought to have DM in 2015 [2]. Thus, Russia is ranked fifth in the top 10 countries with the largest
* Corresponding author at: Dmitriya Ulianova Street 11, 117036 Moscow, Russia. Tel.: +7 985 644 7809. E-mail address: [email protected] (G. Galstyan). 1 Present address: Advisor’s Group of CRA-Club, Moscow, Russia. http://dx.doi.org/10.1016/j.diabres.2016.02.010 0168-8227/# 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
diabetes research and clinical practice 115 (2016) 90–95
population living with DM. However, this estimate might not be reliable as it is extrapolated from diabetes prevalence in the neighbouring countries. An earlier report gave a rather conservative estimate of DM prevalence (3.2%, 3.5 million/ 110 million adult population of Russia) [3], but sample populations previously evaluated were not representative of the general Russian population [4]. Furthermore, more recently, epidemiological studies in several Russian regions have shown that DM prevalence may be greater than previously reported [5]. The inconsistencies in reporting DM prevalence has led to an assumption that a substantial number of individuals in Russia remain undiagnosed. Given the growing economic burden of type 2 DM (T2DM), there is a need to conduct a well-designed, epidemiological study to improve the accuracy of prevalence estimates. In 2013, Russian and French officials met to discuss the prospect of co-operation for conducting a large-scale, epidemiological study, the NATION study, to evaluate accurately T2DM prevalence in Russia [6]. Results of this study would be useful for Public Health authorities in decision making to define health priorities, to develop healthier lifestyles and better diabetes care to eventually reduce T2DM and its complications. The aim of the NATION study was to evaluate the prevalence of T2DM in the adult Russian population, the relationship of T2DM with age, sex and body mass index (BMI), and to compare the prevalence between urban and rural populations. A sampling model was developed to adequately represent the Russian adult population using population data from the Russian Population Census [7].
2.
Materials and methods
2.1.
Study design and recruitment
NATION is a national, epidemiological, cross-sectional study, which was conducted across the eight districts of the Russian Federation from September 2013 to February 2015. Sixty-three regions were included and 188 settlements comprised of 90 cities/towns (urban) and 98 rural settlements. Urban and rural settlements were defined as per the Federal State Statistics Service [7]. Details of the recruitment method are shown in Supplementary Table 1. Adults aged 20–79 years were recruited by age, sex, geographic distribution and type of settlement. Recruitment was conducted in public places with a high concentration of people (e.g. streets, squares, parks and other community areas) in urban areas, and in the streets of rural areas. Subjects were consecutively recruited until quotas for sex, age and settlement type were reached. Any subject who, when asked, stated that they had T1DM was excluded from recruitment. Subjects were asked to complete a survey on socio-economic status, health and lifestyle habits. All subjects provided written informed consent prior to study participation. The study was performed in accordance with applicable ethical principles outlined in the Helsinki Declaration and guidelines for Good Clinical Practice [8,9]. Ethical approval was provided by the Independent Multidisciplinary Committee on Ethical Review of Clinical Trials of the Russian Federation.
2.2.
91
Sampling
For the NATION study, a representative sample frame was constructed based on the general population profile of Russia, i.e. the distribution of the whole Russian population (aged 20– 79 years) and based on Russian regions (population structure based on age, sex, and settlement type). These population data were sourced from the Russian Population Census [7]. A sample size of 26,000 subjects was required so that the diabetes prevalence could be estimated to within 0.6 percentage points of the true value with 95% confidence, assuming an expected prevalence of diabetes equal to 5%. A multi-stage selection method with quotas for age, sex and settlement type was used to design the appropriate sampling frame (see Supplementary Table 2 for full details).
2.3.
T2DM evaluation methodology
A survey based on a structured questionnaire was conducted (Aston Consulting, Moscow, Russia), BMI (without any outer clothing and shoes) was assessed, and whole venous blood samples (2 mL, EDTA tubes; fasting status was not necessary) were collected during laboratory/mobile unit visits. Blood samples were kept at 2–8 8C and transported to a central laboratory (INVITRO, Moscow, Russia) within a maximum of 5 days from collection. HbA1c levels were analyzed by capillary electrophoresis of whole blood [10] using a Capillarys 2 FlexPiercing instrument (Sebia Inc, Norcross, GA, USA). An internal quality control (QC) was performed daily and the between-run coefficient of variability (CV) was <4%, and the mean internal QCs were 5.1% and 5.3%. An external QC of the analysers in the central laboratory compared with all other laboratories in the European Reference Laboratory database in 2013, demonstrated excellent repeatability (CV 1.2%) and linearity (CV 0.9983) of the method. Following data collection, several groups were identified: (1) subjects previously diagnosed as T2DM subjects (anamnestic information), pharmacologically treated or not; (2) subjects previously undiagnosed as T2DM subjects based on HbA1c 6.5% (48 mmol/mol); (3) subjects defined as having prediabetes based on HbA1c 5.7% and <6.5% (39 to <48 mmol/mol) and without a previous T2DM diagnosis.
2.4.
Objectives
The primary objective of the NATION study was to evaluate the prevalence of previously diagnosed and previously undiagnosed T2DM, and pre-diabetes in the adult Russian population. Secondary objectives included evaluation of the urban and rural distributions of T2DM, and T2DM relationship with demographic characteristics (age and sex) and BMI.
2.5.
Statistical analyses
All data (socio-demographic determinants, anthropometric measurements, HbA1c results, and survey responses) were entered into a unified database after the field phase. Statistical analyses were performed using standard data processing packages (SPSS statistical software, version 20.0; SPSS Inc.,
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previously diagnosed T2DM, and 781 (2.9% of overall study population; 95% CI: 2.7–3.1%) had previously undiagnosed T2DM. Thus, the proportion of previously undiagnosed T2DM subjects was 54%. Of the 668 subjects reporting a previous T2DM diagnosis, 3.4% (23/668) were not receiving antihyperglycaemic therapy and 2.4% (16/668) had HbA1c 6.5% (48 mmol/mol). Of the T2DM subjects, 19.3% (278/1449; 95% CI: 18.8–19.8%) had an HbA1c >9% (>75 mmol/mol). Among subjects with previously undiagnosed T2DM, the mean HbA1c was 7.9% (63 mmol/mol) vs. 7.4% (57 mmol/mol) among subjects with previously diagnosed T2DM ( p < 0.001). Of the NATION study population, 19.3% (5128/26,620; 95% CI: 18.8– 19.7%) had pre-diabetes.
Chicago, IL, USA; Excel Microsoft). Descriptive statistics (frequency distribution, absolute values, estimated percentage distribution, mean values, etc.) were used to identify general characteristics pertaining to the study outcomes and to compare data distribution across various groups. Nonparametric comparison tests on two or more independent and dependent samples (Mann Whitney U-test, Kolmogorov– Smirnov test, Waldo–Wolfowitz test, Wilcoxon test, chisquared test, binominal test) were applied to assess differences between parametric and non-parametric data groups. Parametric methods (standard error of the mean, standard deviation, 95% confidence intervals [CI], variance, minimum/ maximum and Student’s t-test) were used to assess differences between two groups of approximately normally distributed, quantitative data. For T2DM risk evaluation, relative risk and odds ratio were evaluated for pair groups (males vs. females, body mass index <25 vs. 25 kg/m2, urban vs. rural settlement). For age analyses, the data were split into categories of 5-year ranges. These 5-year ranges were then combined, as required, for further analysis. As the NATION study population was representative and in proportion with the whole population of Russia, i.e. distribution of age and gender, results were not normalized to account for differences in number and age.
3.3.
Prevalence of T2DM by age and sex
Out of 27,252-screened subjects, 26,620 were eligible and included in NATION. Blood samples collected from 632 subjects were lost or haemolysed during transportation and were not analyzed. Fifty-five percent of subjects (n = 14,611) were female. The overall mean (standard deviation [SD]) age of females, 46.5 (16.3) years, was significantly higher than for males, 43.2 (15.4) years ( p < 0.001). The distribution of the NATION population by sex and age is shown in Supplementary Fig. 1a.
T2DM prevalence increased with age (up to 69 years) then decreased slightly from 70 years. The ratio of previously diagnosed and undiagnosed T2DM also increased with age (Fig. 1). The overall prevalence of T2DM (regardless of age) was significantly higher in females versus males (884/14,611 [6.1%; 95% CI: 5.7–6.5%] vs. 565/12,009 [4.7%; 95% CI: 4.3–5.1%], respectively, p < 0.001). In subjects with T2DM, mean age was significantly higher in females versus males (60.1 vs. 54.8 years, p < 0.001). There were no significant differences between males and females in T2DM prevalence in the age categories 20–44 years (1.4% vs. 1.3% for males and females, respectively) and 45–59 years (7.9% vs. 7.0% for males and females, respectively). In subjects aged 60–79 years, T2DM prevalence was significantly higher in females versus males (14.1% vs. 9.9%, p < 0.001). Overall, of the subjects with T2DM, a higher proportion of females had previously diagnosed T2DM (442/884, 50%) than males (226/565, 40%) ( p = 0.004). The proportions of previously diagnosed T2DM for females versus males varied within different age categories: 40% and 23% in subjects <44 years (not significant), 49% vs. 42% in subjects 45–59 years (not significant) and 52% vs. 45% in subjects >60 years ( p < 0.001), respectively (Fig. 2).
3.2.
3.4.
3.
Results
3.1.
Study population
Prevalence of T2DM and pre-diabetes
In the NATION study, overall, 5.4% (1449/26,620; 95% CI: 5.1– 5.7%) of subjects were diagnosed with T2DM. Among them, 668 (2.5% of overall study population; 95% CI: 2.3–2.7%) had
Prevalence of T2DM by BMI
In NATION, the proportion of subjects who were normal weight (BMI <25 kg/m2), overweight (BMI 25 to <30 kg/m2) or obese (BMI 30 kg/m2) was 34%, 35% and 31%, respectively.
Prevalence (%)
16.0 14.0
Previously diagnosed
12.0
Previously undiagnosed 5.32
10.0
6.29 6.54
8.0 4.99
6.0
4.15
4.0 2.0 0
6.60
0.65
0.83 0.31
0.52 0.30
1.16 0.48
8.31
2.92 1.66 1.09
2.30
3.39
4.51
5.12
6.73
5.70
55–59 60–64 65–69 70–74 75–79 20–24 25–29 30–34 35–39 40–44 45–49 50–54 (n = 2934) (n = 2909) (n = 2681) (n = 2496) (n = 2293) (n = 2565) (n = 2744) (n = 2485) (n = 1973) (n = 1071) (n = 1575) (n = 894) Age (years)
Fig. 1 – Prevalence of previously diagnosed and previously undiagnosed T2DM by age.
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diabetes research and clinical practice 115 (2016) 90–95
Prevalence of previously diagnosed T2DM in various sex-age groups Men (%)
Men vs women p < 0.001
Men vs women p = 0.209
Women (%)
Men (%)
Age (years)
Women (%)
4.7
75–79
6.2
4.3
75–79
7.6
4.5
70–74
7.8
4.9
70–74
7.0
5.6
65–69
9.9
4.9
65–69
5.6
3.8
60–64
6.1
6.4
60–64
6.6
4.2
55–59
4.7
5.3
55–59
4.8
3.2
50–54
3.5
5.1
50–54
3.4
2.5
45–49
2.1
3.4
45–49
2.5
2.1
40–44 1.2
1.0 Men vs women p = 0.048
Age (years)
Prevalence of previously undiagnosed T2DM in various sex-age groups
40–44
1.2
0.3
35–39
0.7
0.2
30–34
0.4
0.7
30–34
0.2
25–29
0.4
0.8
25–29
0.1
20–24
0.1
0.7
20–24
1.4
35–39
0.9
Men vs women p < 0.001
Men vs women p = 0.777
Men vs women p = 0.072
0.4 0.8 0.5
Fig. 2 – Prevalence of previously diagnosed and undiagnosed T2DM, by sex and age.
Prevalence of obesity in subjects 45 years was significantly higher in females versus males ( p < 0.001). The proportion of subjects with pre-diabetes and T2DM increased with increasing BMI. In the BMI <25 kg/m2 group, the prevalence of T2DM was 1.1%, and the prevalence of pre-diabetes was 7.4%. In the BMI 25 to <30 kg/m2 group, the prevalence of T2DM was 3.9%, while the prevalence of pre-diabetes was 18.6%. Among the population classified as obese (BMI 30 kg/m2), the prevalence of T2DM was 12.0% and that of pre-diabetes was 33.1%. These findings indicate a significant increase of the prevalence of T2DM between normal weight and obese subjects ( p < 0.001). In the overall study population, in overweight and obese groups, HbA1c was higher than in the normal weight group (mean HbA1c 5.5% [37 mmol/mol], overweight; 5.8% [40 mmol/ mol] obese; 5.3% [34 mmol/mol] normal weight). The prevalence of T2DM in obese subjects was similar in females and males in all age groups (20–44, 45–59, and 60–79 years of age).
3.5.
T2DM prevalence by settlement type
The proportion of subjects with T2DM was significantly higher in the rural population compared with the urban population (427/6333 [6.7%; 95% CI: 6.1–7.3%] vs. 1022/20,287 [5.0%; 95% CI: 4.7–5.3%], respectively, p < 0.001). The proportion of subjects with previously diagnosed T2DM was 3.0% (188/6333; 95% CI: 2.6–3.4% in the rural population) and 2.4% (480/20,287; 95% CI: 2.2–2.6% in the urban population) ( p < 0.001). The proportion of subjects with previously undiagnosed T2DM was 3.8% (239/ 6333; 95% CI: 3.3–4.3% in the rural population) and 2.7% (542/ 20,287; 95% CI: 2.5–2.9% in the urban population) ( p < 0.001). Average BMI and age were both higher in rural settlements compared with urban settlements (28.1 vs. 27.0 kg/m2, p < 0.001; and 48 years vs. 43 years, p < 0.001, respectively).
4.
Discussion
NATION is the first, national, epidemiological, cross-sectional study with the primary aim to evaluate the prevalence of
T2DM in the Russian adult population. Using population data (age, sex, geographic distribution and settlement type) from the Russian Population Census [7], a representative sample was constructed for the NATION study. The NATION study results demonstrate a 5.4% T2DM prevalence in the Russian adult population with an uneven distribution when stratified by settlement type. A key element of the NATION study was to recruit a sample population representative of the Russian adult population. More females than males were recruited, and the overall mean age of females was higher than for males. Furthermore, the proportion of younger subjects in the NATION study (20–44 and 45–59 years) was greater than that of older participants (60–79 years), with more females than males within each age category. This distribution of the NATION study population by sex and age is similar to that of the overall Russian population reported in the last census [7] (Supplementary Fig. 1b). Thus, given the validity of the population sample, data from the NATION study can be extrapolated to the general Russian population. A previous estimate of T2DM prevalence (previously diagnosed) in Russia was 3.2% [3], which is similar to the prevalence of previously diagnosed T2DM in the NATION study. The agreement between the NATION study and the State Diabetes registry estimates of the prevalence of previously diagnosed T2DM confirm the validity of the latter. The small difference between these prevalence estimates could be explained by the recruitment of subjects in public places in the NATION study (a study limitation). Extrapolation of the T2DM prevalence reported in the NATION study indicates that, in the adult Russian population aged 20–79 years, 5.9 million people, estimated using Federal State Stats Service, 2010 data (108 million people aged 20–79 years) were likely to have T2DM. The NATION study also shows that a substantial proportion (54%) of T2DM cases are not diagnosed in Russia. Previously diagnosed T2DM was found more frequently than previously undiagnosed T2DM in subjects aged 65 years old, which may be due to an increase in screening for diabetes in older people. In addition, the NATION study reported a high prevalence of pre-diabetes (19.3%),
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diabetes research and clinical practice 115 (2016) 90–95
accounting for an extrapolated population of 20.7 million people in Russia in 2014. The NATION study also reported a high incidence of subjects with T2DM with Hb1Ac >9%, who, therefore, require urgent appropriate antihyperglycaemic treatment. In the NATION study, T2DM prevalence increased with age, which is in keeping with previous reports [2,11]. The highest T2DM prevalence in the NATION study was in subjects aged 65–69 years, which is consistent with recent US data, where the prevalence of T2DM in subjects 65 years is 24.7% [11]. This finding is important, as in this age group there is a high prevalence of cardiovascular disease, management of which is more difficult in the presence of diabetes [12,13]. Although T2DM prevalence increased with age, in those aged 70 years it does not increase. This observation may be linked to survival bias with a high mortality rate due to increased risk of cardiovascular disease in subjects with diabetes at a younger age [14]. With regard to sex, the present study indicated that T2DM prevalence was significantly greater among females versus males in the whole study population. This finding is in contrast with earlier reports where the prevalence of T2DM is generally higher in males than females [2,15,16]. In the NATION study, the sex difference in T2DM prevalence may be driven by age, as the female population is significantly older than the male one, which is supported by ageadjustment of T2DM prevalence demonstrating no significant differences between males (5.1%; 95% CI: 4.8–5.4%) and females (5.6%; 95% CI: 5.3–5.9%). Additionally, considering results across the different age groups, the higher T2DM prevalence in females versus males was only statistically significant in subjects aged 60 years, which may be explained by a survival bias due to higher cardiovascularrelated mortality in men than in women [17–19]. Interestingly, the proportion of females with previously diagnosed T2DM was higher than in males across nearly all age groups. This observation may reflect a more frequent screening of women for T2DM, e.g. during pregnancy and menopause or due to more frequent obesity. The NATION study also demonstrated that T2DM prevalence increased with increasing BMI and obesity, as would be expected as obesity is a causal risk factor for T2DM [20]. When stratified by settlement type, T2DM prevalence was found to vary in urban or rural areas. Interestingly, the proportion of subjects with T2DM was significantly higher in those living in rural versus urban settlements. This difference in T2DM rates may be explained by the finding that BMI and age were both significantly higher in rural areas versus urban areas. Strengths of the NATION study include the recruitment of subjects based on the population distribution of the whole Russian population, as reported by the Russia Population Census [7]. The ratio of females to males in the NATION study was 55:45%. This ratio is consistent with that reported for the overall Russian population i.e. 54:46% [7], that has been stable from 1926 to 2014. Also, there was a predominance of younger subjects in the NATION study population. This is particularly relevant given that Russia has a younger population distribution when compared with other European countries [21]. Indeed, normalizing the NATION study data based on the
European age structure in accordance with Eurostat statistics indicates a standardized prevalence of T2DM of 5.9%. One limitation of the NATION study is that initial patient diagnosis categorization was based on self declaration, with subsequent HbA1c testing. Additionally, the use of HbA1c alone as a tool for the diagnosis of T2DM may not be sufficient. The adoption of HbA1c is a relatively new approach for the diagnosis of diabetes, which has yet to be fully standardized. Well known factors, such as anaemia [22] or certain chronic diseases [23] can affect HbA1c values. Other investigations have concluded that using HbA1c alone could result in under-diagnosis of T2DM [24,25], or that this test should be combined with other tests to improve detection rates (e.g. fasting glucose [26]). On the other hand, other studies have demonstrated that HbA1c is a useful tool for diabetes screening (e.g. [27]). Another limitation of the NATION study is that the results represent T2DM prevalence only in the most active population (e.g. those individuals who frequent public areas). T2DM prevalence in a less-active population (e.g. those who are more likely to be house-bound due to age and/or underlying co-morbidities) is likely to be even higher. This should be considered amongst the possible factors influencing the decline of prevalence in older ages. In conclusion, the NATION study is the first, national, epidemiological, cross-sectional study conducted in Russia to evaluate the nationwide prevalence of T2DM. As hypothesized, the prevalence of T2DM in the adult Russia population was higher than previously registered [3], with more than 50% of subjects having undiagnosed T2DM. These findings highlight a growing concern for the national burden of T2DM across Russia. The increasing prevalence of T2DM with the risk of diabetes-related complications will undoubtedly add to health care requirements. The results of the NATION study provide valuable information to support the design and implementation of an effective prevention and management national diabetes programme in Russia.
Conflict of interest ID declares no conflicts of interest. MS declares speaker honorarium from Novo Nordisk, Sanofi-Aventis, Novartis, Merck Sharp & Dohme, AstraZeneca and Servier, and advisory panels for Novo Nordisk and AstraZeneca. GG has participated in advisory panels for Merck Sharp & Dohme, AstraZeneca and Novo Nordisk, in speaker bureaus for Eli Lilly, Novo Nordisk, Sanofi, Novartis, Berlin Chemie, and Merck Sharp & Dohme, and has received research support from BC Pharma and Novartis. MMB declares consultancy honorarium from SanofiAventis, membership of the Novo Nordisk DAWN2 Study IPPC, and speaker honorarium from Nextlevel. DS has served on speaker bureaus for Lifescan, Lilly-France and Sanofi-Aventis, and advisory panels for AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis and Takeda; has received sponsorship to organize scientific meetings from GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Novartis, Sanofi-Aventis and Takeda; has participated as an investigator in studies conducted by LillyFrance and Novartis. IP was an employee of Sanofi-Aventis Russia when the study was conducted.
diabetes research and clinical practice 115 (2016) 90–95
Author contributions All authors are members of the NATION Study Steering Committee. ID, MS, GG and IP were co-authors of the study protocol. ID, MS, MMB, IP and GG contributed to the conception and design of the study. All authors contributed to data analysis, data interpretation and reviewed drafts of the manuscript and approved the final draft for submission.
Acknowledgements The study was funded by Sanofi-Aventis Russia. The authors acknowledge Tracey McManus and Jackie Phillipson of Zoetic Science, part of KnowledgePoint360, an Ashfield Company for assistance in providing medical writing support in the development of this manuscript. Medical writing support was funded by Sanofi-Aventis Russia, Moscow, Russia.
Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j. diabres.2016.02.010.
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[10] Doelman CJ, Siebelder CW, Nijhof WA, Weykamp CW, Janssens J, Penders TJ. Capillary electrophoresis system for haemoglobin A1c determinations evaluated. Clin Chem 1997;644–8. [11] Menke A, Casagrande S, Geiss L, Cowie CC. Prevalence of and trends in diabetes among adults in the United States, 1988–2012. JAMA 2015;314:1021–9. [12] Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics – 2015 update: a report from the American Heart Association. Circulation 2015;131:e29–322. [13] Gyberg V, De Bacquer D, De Backer G, Jennings C, Kotseva K, Mellbin L, et al. Patients with coronary artery disease and diabetes need improved management: a report from the EUROASPIRE IV survey: a registry from the EuroObservational Research Programme of the European Society of Cardiology. Cardiovasc Diabetol 2015;14:133. [14] Singh GM, Danaei G, Farzadfar F, Stevens GA, Woodward M, Wormser D, et al. The age-specific quantitative effects of metabolic risk factors on cardiovascular diseases and diabetes: a pooled analysis. PLOS ONE 2013;8:e65174. [15] Wa¨ndell PE, Carlsson AC. Gender differences and time trends in incidence and prevalence of type 2 diabetes in Sweden – a model explaining the diabetes epidemic worldwide today? Diabetes Res Clin Pract 2014;106:e90–2. [16] Sattar N. Gender aspects in type 2 diabetes mellitus and cardiometabolic risk. Best Pract Res Clin Endocrinol Metab 2013;27:501–7. [17] Nichols M, Townsend N, Scarborough P, Rayner M. Cardiovascular disease in Europe 2014: epidemiological update. Eur Heart J 2014;35:2950–9. [18] Petrukhin IS, Lunina EY. Cardiovascular disease risk factors and mortality in Russia: challenges and barriers. Public Health Rev 2012;33:436–49. [19] Grigoriev P, Mesle´ F, Shkolnikov VM, Andreev E, Fihel A, Pechholdova M, et al. The recent mortality decline in russia: beginning of the cardiovascular revolution? Popul Dev Rev 2014;40:107–29. [20] Sattar N, Gill JM. Type 2 diabetes as a disease of ectopic fat? BMC Med 2014;12:123. [21] Gavrilova NS, Gavrilov LA. Rapidly aging populations: Russia/Eastern Europe. In: Uhlenberg P, editor. International handbook of population aging. New York, NY: Springer; 2009. p. 113–32. http://dx.doi.org/10.1007/978-14020-8356-3_6. [22] English E, Idris I, Smith G, Dhatariya K, Kilpatrick ES, John WG. The effect of anaemia and abnormalities of erthyrocyte indices on HbA1c analysis: a systematic review. Diabetologia 2015;58:1409–21. [23] Jaisson S, Pietrement C, Gillery P. Carbamylation-derived products: bioactive compounds and potential biomarkers in chronic renal failure and atherosclerosis. Clin Chem 2011;57:1499–505. [24] Hage C, Lundman P, Ryde´n L, Mellbin L. Fasting glucose, HbA1c, or oral glucose tolerance testing for detection of glucose abnormalities in patients with acute coronary syndromes. Eur J Prev Cardiol 2013;20:549–54. [25] Farhan S, Jarai R, Tentzeris I, Kautzky-Willer A, Samaha E, Smetana P, et al. Comparison of AbA1c and oral glucose tolerance test for diagnosis of diabetes in patient with coronary artery disease. Clin Res Cardiol 2012;101:625–30. [26] Mo M, Zhong W, Zhao G, Ruan Y, Zhang H, Shi L, et al. Combining glycosylated haemoglobin A1c and fasting plasma glucose for diagnosis of type 2 diabetes in Chinese adults. BMC Endocr Disord 2013;13:44. [27] Steylen PMJ, van der Heijden FMMA, Hoogendijk WJG, Verhoeven WMA. Glycosylated haemoglobin as a screening test for hyperglycemia in antipsychotic-treated patients: a follow-up study. Diabetes Metab Syndr Obes 2015;8:57–63.
Contents available at ScienceDirect
Diabetes Research and Clinical Practice jou rnal hom ep ag e: w ww.e l s e v i er . c om/ loca te / d i ab r es
Prevalence of type 2 diabetes mellitus (T2DM) in the adult Russian population (NATION study) Ivan Dedov a, Marina Shestakova a,b, Massimo Massi Benedetti c, Dominique Simon d, Iakov Pakhomov e,1, Gagik Galstyan a,b,* a
Endocrinology Research Centre, Moscow, Russia I.M. Sechenov First Moscow State Medical University, Moscow, Russia c Hub for International Health Research (HIRS), Perugia, Italy d Diabetes Department and Institute of Cardiometabolism and Metabolism (ICAN), Pitie´-Salpe´trie`re Hospital, Paris, France e Sanofi-Aventis Russia, Moscow, Russia b
article info
abstract
Article history:
Aim: To estimate type 2 diabetes mellitus (T2DM) prevalence in Russian adults.
Received 22 December 2015
Methods: NATION is a national, epidemiological, cross-sectional study, conducted in Russia.
Accepted 24 February 2016
In adults (aged 20–79 years), recruitment was stratified by age, sex, geographic region and
Available online 2 March 2016
settlement type to obtain a representative sample. Recruitment was in public areas with high numbers of people. T2DM was diagnosed by glycated haemoglobin A1c (HbA1c) levels
Keywords:
(diabetes: HbA1c 6.5% [48 mmol/mol]; pre-diabetes: HbA1c 5.7 to <6.5% [39 to
Diabetes mellitus, type 2
<48 mmol/mol]). Socio-demographic and anthropometric data were collected.
Epidemiological study
Results: Blood samples from 26,620 subjects were available. Overall, 5.4% were diagnosed
Undiagnosed diabetes mellitus
with T2DM (previously diagnosed: 2.5%; previously undiagnosed: 2.9%); 19.3% were pre-
Prevalence
diabetic. T2DM prevalence increased with age (up to 70 years) and was higher among
Russia
females than males (6.1% vs. 4.7%, p < 0.001). The estimated proportion of subjects with prediabetes and T2DM tended to increase with increasing body mass index. T2DM prevalence was higher in rural versus urban populations (6.7% vs. 5.0%, p < 0.001). Conclusion: In the Russian adult population, 19.3% had pre-diabetes, T2DM prevalence was 5.4%, and 54% of subjects with diabetes were previously undiagnosed. These results may help to develop a new T2DM predictive, preventative and management programme in Russia. # 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1.
Introduction
Prevalence of diabetes mellitus (DM) is growing worldwide and has reached epidemic proportions in many developing and most developed countries [1,2]. A recent report noted an
estimated prevalence of diabetes of 9.2% (uncertainty interval 4.7–13.3%) for the adult population aged 20–79 years in Russia [2]. According to this estimated prevalence, in Russia, 12.1 million (uncertainty interval 6.2–17.0 million) people aged 20–79 years old are thought to have DM in 2015 [2]. Thus, Russia is ranked fifth in the top 10 countries with the largest
* Corresponding author at: Dmitriya Ulianova Street 11, 117036 Moscow, Russia. Tel.: +7 985 644 7809. E-mail address: [email protected] (G. Galstyan). 1 Present address: Advisor’s Group of CRA-Club, Moscow, Russia. http://dx.doi.org/10.1016/j.diabres.2016.02.010 0168-8227/# 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
diabetes research and clinical practice 115 (2016) 90–95
population living with DM. However, this estimate might not be reliable as it is extrapolated from diabetes prevalence in the neighbouring countries. An earlier report gave a rather conservative estimate of DM prevalence (3.2%, 3.5 million/ 110 million adult population of Russia) [3], but sample populations previously evaluated were not representative of the general Russian population [4]. Furthermore, more recently, epidemiological studies in several Russian regions have shown that DM prevalence may be greater than previously reported [5]. The inconsistencies in reporting DM prevalence has led to an assumption that a substantial number of individuals in Russia remain undiagnosed. Given the growing economic burden of type 2 DM (T2DM), there is a need to conduct a well-designed, epidemiological study to improve the accuracy of prevalence estimates. In 2013, Russian and French officials met to discuss the prospect of co-operation for conducting a large-scale, epidemiological study, the NATION study, to evaluate accurately T2DM prevalence in Russia [6]. Results of this study would be useful for Public Health authorities in decision making to define health priorities, to develop healthier lifestyles and better diabetes care to eventually reduce T2DM and its complications. The aim of the NATION study was to evaluate the prevalence of T2DM in the adult Russian population, the relationship of T2DM with age, sex and body mass index (BMI), and to compare the prevalence between urban and rural populations. A sampling model was developed to adequately represent the Russian adult population using population data from the Russian Population Census [7].
2.
Materials and methods
2.1.
Study design and recruitment
NATION is a national, epidemiological, cross-sectional study, which was conducted across the eight districts of the Russian Federation from September 2013 to February 2015. Sixty-three regions were included and 188 settlements comprised of 90 cities/towns (urban) and 98 rural settlements. Urban and rural settlements were defined as per the Federal State Statistics Service [7]. Details of the recruitment method are shown in Supplementary Table 1. Adults aged 20–79 years were recruited by age, sex, geographic distribution and type of settlement. Recruitment was conducted in public places with a high concentration of people (e.g. streets, squares, parks and other community areas) in urban areas, and in the streets of rural areas. Subjects were consecutively recruited until quotas for sex, age and settlement type were reached. Any subject who, when asked, stated that they had T1DM was excluded from recruitment. Subjects were asked to complete a survey on socio-economic status, health and lifestyle habits. All subjects provided written informed consent prior to study participation. The study was performed in accordance with applicable ethical principles outlined in the Helsinki Declaration and guidelines for Good Clinical Practice [8,9]. Ethical approval was provided by the Independent Multidisciplinary Committee on Ethical Review of Clinical Trials of the Russian Federation.
2.2.
91
Sampling
For the NATION study, a representative sample frame was constructed based on the general population profile of Russia, i.e. the distribution of the whole Russian population (aged 20– 79 years) and based on Russian regions (population structure based on age, sex, and settlement type). These population data were sourced from the Russian Population Census [7]. A sample size of 26,000 subjects was required so that the diabetes prevalence could be estimated to within 0.6 percentage points of the true value with 95% confidence, assuming an expected prevalence of diabetes equal to 5%. A multi-stage selection method with quotas for age, sex and settlement type was used to design the appropriate sampling frame (see Supplementary Table 2 for full details).
2.3.
T2DM evaluation methodology
A survey based on a structured questionnaire was conducted (Aston Consulting, Moscow, Russia), BMI (without any outer clothing and shoes) was assessed, and whole venous blood samples (2 mL, EDTA tubes; fasting status was not necessary) were collected during laboratory/mobile unit visits. Blood samples were kept at 2–8 8C and transported to a central laboratory (INVITRO, Moscow, Russia) within a maximum of 5 days from collection. HbA1c levels were analyzed by capillary electrophoresis of whole blood [10] using a Capillarys 2 FlexPiercing instrument (Sebia Inc, Norcross, GA, USA). An internal quality control (QC) was performed daily and the between-run coefficient of variability (CV) was <4%, and the mean internal QCs were 5.1% and 5.3%. An external QC of the analysers in the central laboratory compared with all other laboratories in the European Reference Laboratory database in 2013, demonstrated excellent repeatability (CV 1.2%) and linearity (CV 0.9983) of the method. Following data collection, several groups were identified: (1) subjects previously diagnosed as T2DM subjects (anamnestic information), pharmacologically treated or not; (2) subjects previously undiagnosed as T2DM subjects based on HbA1c 6.5% (48 mmol/mol); (3) subjects defined as having prediabetes based on HbA1c 5.7% and <6.5% (39 to <48 mmol/mol) and without a previous T2DM diagnosis.
2.4.
Objectives
The primary objective of the NATION study was to evaluate the prevalence of previously diagnosed and previously undiagnosed T2DM, and pre-diabetes in the adult Russian population. Secondary objectives included evaluation of the urban and rural distributions of T2DM, and T2DM relationship with demographic characteristics (age and sex) and BMI.
2.5.
Statistical analyses
All data (socio-demographic determinants, anthropometric measurements, HbA1c results, and survey responses) were entered into a unified database after the field phase. Statistical analyses were performed using standard data processing packages (SPSS statistical software, version 20.0; SPSS Inc.,
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previously diagnosed T2DM, and 781 (2.9% of overall study population; 95% CI: 2.7–3.1%) had previously undiagnosed T2DM. Thus, the proportion of previously undiagnosed T2DM subjects was 54%. Of the 668 subjects reporting a previous T2DM diagnosis, 3.4% (23/668) were not receiving antihyperglycaemic therapy and 2.4% (16/668) had HbA1c 6.5% (48 mmol/mol). Of the T2DM subjects, 19.3% (278/1449; 95% CI: 18.8–19.8%) had an HbA1c >9% (>75 mmol/mol). Among subjects with previously undiagnosed T2DM, the mean HbA1c was 7.9% (63 mmol/mol) vs. 7.4% (57 mmol/mol) among subjects with previously diagnosed T2DM ( p < 0.001). Of the NATION study population, 19.3% (5128/26,620; 95% CI: 18.8– 19.7%) had pre-diabetes.
Chicago, IL, USA; Excel Microsoft). Descriptive statistics (frequency distribution, absolute values, estimated percentage distribution, mean values, etc.) were used to identify general characteristics pertaining to the study outcomes and to compare data distribution across various groups. Nonparametric comparison tests on two or more independent and dependent samples (Mann Whitney U-test, Kolmogorov– Smirnov test, Waldo–Wolfowitz test, Wilcoxon test, chisquared test, binominal test) were applied to assess differences between parametric and non-parametric data groups. Parametric methods (standard error of the mean, standard deviation, 95% confidence intervals [CI], variance, minimum/ maximum and Student’s t-test) were used to assess differences between two groups of approximately normally distributed, quantitative data. For T2DM risk evaluation, relative risk and odds ratio were evaluated for pair groups (males vs. females, body mass index <25 vs. 25 kg/m2, urban vs. rural settlement). For age analyses, the data were split into categories of 5-year ranges. These 5-year ranges were then combined, as required, for further analysis. As the NATION study population was representative and in proportion with the whole population of Russia, i.e. distribution of age and gender, results were not normalized to account for differences in number and age.
3.3.
Prevalence of T2DM by age and sex
Out of 27,252-screened subjects, 26,620 were eligible and included in NATION. Blood samples collected from 632 subjects were lost or haemolysed during transportation and were not analyzed. Fifty-five percent of subjects (n = 14,611) were female. The overall mean (standard deviation [SD]) age of females, 46.5 (16.3) years, was significantly higher than for males, 43.2 (15.4) years ( p < 0.001). The distribution of the NATION population by sex and age is shown in Supplementary Fig. 1a.
T2DM prevalence increased with age (up to 69 years) then decreased slightly from 70 years. The ratio of previously diagnosed and undiagnosed T2DM also increased with age (Fig. 1). The overall prevalence of T2DM (regardless of age) was significantly higher in females versus males (884/14,611 [6.1%; 95% CI: 5.7–6.5%] vs. 565/12,009 [4.7%; 95% CI: 4.3–5.1%], respectively, p < 0.001). In subjects with T2DM, mean age was significantly higher in females versus males (60.1 vs. 54.8 years, p < 0.001). There were no significant differences between males and females in T2DM prevalence in the age categories 20–44 years (1.4% vs. 1.3% for males and females, respectively) and 45–59 years (7.9% vs. 7.0% for males and females, respectively). In subjects aged 60–79 years, T2DM prevalence was significantly higher in females versus males (14.1% vs. 9.9%, p < 0.001). Overall, of the subjects with T2DM, a higher proportion of females had previously diagnosed T2DM (442/884, 50%) than males (226/565, 40%) ( p = 0.004). The proportions of previously diagnosed T2DM for females versus males varied within different age categories: 40% and 23% in subjects <44 years (not significant), 49% vs. 42% in subjects 45–59 years (not significant) and 52% vs. 45% in subjects >60 years ( p < 0.001), respectively (Fig. 2).
3.2.
3.4.
3.
Results
3.1.
Study population
Prevalence of T2DM and pre-diabetes
In the NATION study, overall, 5.4% (1449/26,620; 95% CI: 5.1– 5.7%) of subjects were diagnosed with T2DM. Among them, 668 (2.5% of overall study population; 95% CI: 2.3–2.7%) had
Prevalence of T2DM by BMI
In NATION, the proportion of subjects who were normal weight (BMI <25 kg/m2), overweight (BMI 25 to <30 kg/m2) or obese (BMI 30 kg/m2) was 34%, 35% and 31%, respectively.
Prevalence (%)
16.0 14.0
Previously diagnosed
12.0
Previously undiagnosed 5.32
10.0
6.29 6.54
8.0 4.99
6.0
4.15
4.0 2.0 0
6.60
0.65
0.83 0.31
0.52 0.30
1.16 0.48
8.31
2.92 1.66 1.09
2.30
3.39
4.51
5.12
6.73
5.70
55–59 60–64 65–69 70–74 75–79 20–24 25–29 30–34 35–39 40–44 45–49 50–54 (n = 2934) (n = 2909) (n = 2681) (n = 2496) (n = 2293) (n = 2565) (n = 2744) (n = 2485) (n = 1973) (n = 1071) (n = 1575) (n = 894) Age (years)
Fig. 1 – Prevalence of previously diagnosed and previously undiagnosed T2DM by age.
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Prevalence of previously diagnosed T2DM in various sex-age groups Men (%)
Men vs women p < 0.001
Men vs women p = 0.209
Women (%)
Men (%)
Age (years)
Women (%)
4.7
75–79
6.2
4.3
75–79
7.6
4.5
70–74
7.8
4.9
70–74
7.0
5.6
65–69
9.9
4.9
65–69
5.6
3.8
60–64
6.1
6.4
60–64
6.6
4.2
55–59
4.7
5.3
55–59
4.8
3.2
50–54
3.5
5.1
50–54
3.4
2.5
45–49
2.1
3.4
45–49
2.5
2.1
40–44 1.2
1.0 Men vs women p = 0.048
Age (years)
Prevalence of previously undiagnosed T2DM in various sex-age groups
40–44
1.2
0.3
35–39
0.7
0.2
30–34
0.4
0.7
30–34
0.2
25–29
0.4
0.8
25–29
0.1
20–24
0.1
0.7
20–24
1.4
35–39
0.9
Men vs women p < 0.001
Men vs women p = 0.777
Men vs women p = 0.072
0.4 0.8 0.5
Fig. 2 – Prevalence of previously diagnosed and undiagnosed T2DM, by sex and age.
Prevalence of obesity in subjects 45 years was significantly higher in females versus males ( p < 0.001). The proportion of subjects with pre-diabetes and T2DM increased with increasing BMI. In the BMI <25 kg/m2 group, the prevalence of T2DM was 1.1%, and the prevalence of pre-diabetes was 7.4%. In the BMI 25 to <30 kg/m2 group, the prevalence of T2DM was 3.9%, while the prevalence of pre-diabetes was 18.6%. Among the population classified as obese (BMI 30 kg/m2), the prevalence of T2DM was 12.0% and that of pre-diabetes was 33.1%. These findings indicate a significant increase of the prevalence of T2DM between normal weight and obese subjects ( p < 0.001). In the overall study population, in overweight and obese groups, HbA1c was higher than in the normal weight group (mean HbA1c 5.5% [37 mmol/mol], overweight; 5.8% [40 mmol/ mol] obese; 5.3% [34 mmol/mol] normal weight). The prevalence of T2DM in obese subjects was similar in females and males in all age groups (20–44, 45–59, and 60–79 years of age).
3.5.
T2DM prevalence by settlement type
The proportion of subjects with T2DM was significantly higher in the rural population compared with the urban population (427/6333 [6.7%; 95% CI: 6.1–7.3%] vs. 1022/20,287 [5.0%; 95% CI: 4.7–5.3%], respectively, p < 0.001). The proportion of subjects with previously diagnosed T2DM was 3.0% (188/6333; 95% CI: 2.6–3.4% in the rural population) and 2.4% (480/20,287; 95% CI: 2.2–2.6% in the urban population) ( p < 0.001). The proportion of subjects with previously undiagnosed T2DM was 3.8% (239/ 6333; 95% CI: 3.3–4.3% in the rural population) and 2.7% (542/ 20,287; 95% CI: 2.5–2.9% in the urban population) ( p < 0.001). Average BMI and age were both higher in rural settlements compared with urban settlements (28.1 vs. 27.0 kg/m2, p < 0.001; and 48 years vs. 43 years, p < 0.001, respectively).
4.
Discussion
NATION is the first, national, epidemiological, cross-sectional study with the primary aim to evaluate the prevalence of
T2DM in the Russian adult population. Using population data (age, sex, geographic distribution and settlement type) from the Russian Population Census [7], a representative sample was constructed for the NATION study. The NATION study results demonstrate a 5.4% T2DM prevalence in the Russian adult population with an uneven distribution when stratified by settlement type. A key element of the NATION study was to recruit a sample population representative of the Russian adult population. More females than males were recruited, and the overall mean age of females was higher than for males. Furthermore, the proportion of younger subjects in the NATION study (20–44 and 45–59 years) was greater than that of older participants (60–79 years), with more females than males within each age category. This distribution of the NATION study population by sex and age is similar to that of the overall Russian population reported in the last census [7] (Supplementary Fig. 1b). Thus, given the validity of the population sample, data from the NATION study can be extrapolated to the general Russian population. A previous estimate of T2DM prevalence (previously diagnosed) in Russia was 3.2% [3], which is similar to the prevalence of previously diagnosed T2DM in the NATION study. The agreement between the NATION study and the State Diabetes registry estimates of the prevalence of previously diagnosed T2DM confirm the validity of the latter. The small difference between these prevalence estimates could be explained by the recruitment of subjects in public places in the NATION study (a study limitation). Extrapolation of the T2DM prevalence reported in the NATION study indicates that, in the adult Russian population aged 20–79 years, 5.9 million people, estimated using Federal State Stats Service, 2010 data (108 million people aged 20–79 years) were likely to have T2DM. The NATION study also shows that a substantial proportion (54%) of T2DM cases are not diagnosed in Russia. Previously diagnosed T2DM was found more frequently than previously undiagnosed T2DM in subjects aged 65 years old, which may be due to an increase in screening for diabetes in older people. In addition, the NATION study reported a high prevalence of pre-diabetes (19.3%),
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accounting for an extrapolated population of 20.7 million people in Russia in 2014. The NATION study also reported a high incidence of subjects with T2DM with Hb1Ac >9%, who, therefore, require urgent appropriate antihyperglycaemic treatment. In the NATION study, T2DM prevalence increased with age, which is in keeping with previous reports [2,11]. The highest T2DM prevalence in the NATION study was in subjects aged 65–69 years, which is consistent with recent US data, where the prevalence of T2DM in subjects 65 years is 24.7% [11]. This finding is important, as in this age group there is a high prevalence of cardiovascular disease, management of which is more difficult in the presence of diabetes [12,13]. Although T2DM prevalence increased with age, in those aged 70 years it does not increase. This observation may be linked to survival bias with a high mortality rate due to increased risk of cardiovascular disease in subjects with diabetes at a younger age [14]. With regard to sex, the present study indicated that T2DM prevalence was significantly greater among females versus males in the whole study population. This finding is in contrast with earlier reports where the prevalence of T2DM is generally higher in males than females [2,15,16]. In the NATION study, the sex difference in T2DM prevalence may be driven by age, as the female population is significantly older than the male one, which is supported by ageadjustment of T2DM prevalence demonstrating no significant differences between males (5.1%; 95% CI: 4.8–5.4%) and females (5.6%; 95% CI: 5.3–5.9%). Additionally, considering results across the different age groups, the higher T2DM prevalence in females versus males was only statistically significant in subjects aged 60 years, which may be explained by a survival bias due to higher cardiovascularrelated mortality in men than in women [17–19]. Interestingly, the proportion of females with previously diagnosed T2DM was higher than in males across nearly all age groups. This observation may reflect a more frequent screening of women for T2DM, e.g. during pregnancy and menopause or due to more frequent obesity. The NATION study also demonstrated that T2DM prevalence increased with increasing BMI and obesity, as would be expected as obesity is a causal risk factor for T2DM [20]. When stratified by settlement type, T2DM prevalence was found to vary in urban or rural areas. Interestingly, the proportion of subjects with T2DM was significantly higher in those living in rural versus urban settlements. This difference in T2DM rates may be explained by the finding that BMI and age were both significantly higher in rural areas versus urban areas. Strengths of the NATION study include the recruitment of subjects based on the population distribution of the whole Russian population, as reported by the Russia Population Census [7]. The ratio of females to males in the NATION study was 55:45%. This ratio is consistent with that reported for the overall Russian population i.e. 54:46% [7], that has been stable from 1926 to 2014. Also, there was a predominance of younger subjects in the NATION study population. This is particularly relevant given that Russia has a younger population distribution when compared with other European countries [21]. Indeed, normalizing the NATION study data based on the
European age structure in accordance with Eurostat statistics indicates a standardized prevalence of T2DM of 5.9%. One limitation of the NATION study is that initial patient diagnosis categorization was based on self declaration, with subsequent HbA1c testing. Additionally, the use of HbA1c alone as a tool for the diagnosis of T2DM may not be sufficient. The adoption of HbA1c is a relatively new approach for the diagnosis of diabetes, which has yet to be fully standardized. Well known factors, such as anaemia [22] or certain chronic diseases [23] can affect HbA1c values. Other investigations have concluded that using HbA1c alone could result in under-diagnosis of T2DM [24,25], or that this test should be combined with other tests to improve detection rates (e.g. fasting glucose [26]). On the other hand, other studies have demonstrated that HbA1c is a useful tool for diabetes screening (e.g. [27]). Another limitation of the NATION study is that the results represent T2DM prevalence only in the most active population (e.g. those individuals who frequent public areas). T2DM prevalence in a less-active population (e.g. those who are more likely to be house-bound due to age and/or underlying co-morbidities) is likely to be even higher. This should be considered amongst the possible factors influencing the decline of prevalence in older ages. In conclusion, the NATION study is the first, national, epidemiological, cross-sectional study conducted in Russia to evaluate the nationwide prevalence of T2DM. As hypothesized, the prevalence of T2DM in the adult Russia population was higher than previously registered [3], with more than 50% of subjects having undiagnosed T2DM. These findings highlight a growing concern for the national burden of T2DM across Russia. The increasing prevalence of T2DM with the risk of diabetes-related complications will undoubtedly add to health care requirements. The results of the NATION study provide valuable information to support the design and implementation of an effective prevention and management national diabetes programme in Russia.
Conflict of interest ID declares no conflicts of interest. MS declares speaker honorarium from Novo Nordisk, Sanofi-Aventis, Novartis, Merck Sharp & Dohme, AstraZeneca and Servier, and advisory panels for Novo Nordisk and AstraZeneca. GG has participated in advisory panels for Merck Sharp & Dohme, AstraZeneca and Novo Nordisk, in speaker bureaus for Eli Lilly, Novo Nordisk, Sanofi, Novartis, Berlin Chemie, and Merck Sharp & Dohme, and has received research support from BC Pharma and Novartis. MMB declares consultancy honorarium from SanofiAventis, membership of the Novo Nordisk DAWN2 Study IPPC, and speaker honorarium from Nextlevel. DS has served on speaker bureaus for Lifescan, Lilly-France and Sanofi-Aventis, and advisory panels for AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis and Takeda; has received sponsorship to organize scientific meetings from GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Novartis, Sanofi-Aventis and Takeda; has participated as an investigator in studies conducted by LillyFrance and Novartis. IP was an employee of Sanofi-Aventis Russia when the study was conducted.
diabetes research and clinical practice 115 (2016) 90–95
Author contributions All authors are members of the NATION Study Steering Committee. ID, MS, GG and IP were co-authors of the study protocol. ID, MS, MMB, IP and GG contributed to the conception and design of the study. All authors contributed to data analysis, data interpretation and reviewed drafts of the manuscript and approved the final draft for submission.
Acknowledgements The study was funded by Sanofi-Aventis Russia. The authors acknowledge Tracey McManus and Jackie Phillipson of Zoetic Science, part of KnowledgePoint360, an Ashfield Company for assistance in providing medical writing support in the development of this manuscript. Medical writing support was funded by Sanofi-Aventis Russia, Moscow, Russia.
Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j. diabres.2016.02.010.
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