Discussion
In this study we compared the prevalence of diabetes in two population-based studies conducted in Russia and Norway using the same case definitions. We found much higher prevalence of diabetes in KYH (11.6% in men and 13.2% in women) compared with Tromsø 7 (6.2% in men and 4.3% in women). The prevalence of diabetes was higher in women than in men in the Russian sample, which is the opposite of what is observed in Norway and other countries.4 5 We also found that there is a higher proportion of undiagnosed diabetes in Russia than in Norway, with proportions of previously undiagnosed diabetes of 36.9% among men and 26.8% among women in KYH.
We attempted to explain the differences in prevalence of diabetes between the two countries using mediation analysis and found that adiposity measured by BMI and WC could explain up to 46% of the difference in diabetes prevalence between studies in women, but did not explain the differences between studies observed in men. Taking further account of smoking and hsCRP as mediation factors in addition to adiposity could explain 55.5% of the differences in diabetes prevalence between studies in women.
Our estimates of diabetes prevalence in Russia are in line with previous studies, although not all of them are published in the peer review literature or contain sufficient detail on age-specific diabetes prevalence.7 10 11 23 Two recent multiregion studies in Russia reported age-specific prevalence of diabetes and found that women at older ages have higher prevalence of diabetes than men.8 9 The NATION study (2013–2015) estimated type 2 diabetes prevalence based on both HbA1c and self-report: 7.0% of women vs 7.9% of men aged 45–59 years old and 14.1% of women vs 9.9% of men aged 60–79 years had diabetes.8 The ESSE-RF study (10 regions of the Russian Federation, 2012–2014) estimated the prevalence of diabetes mellitus based on self-report and fasting glucose: 9.4% of men and 7.4% of women aged 45–54 years old and 13.6% of men and 16.5% of women aged 55–64 years old had diabetes mellitus.9 Similarly to our study, other studies conducted in Russia report that a high proportion of diabetes is undiagnosed: 54% in NATION study,8 43% in HAPIEE,10 and 27% in UEMS.11 Differences between these estimates and estimates from our study can be explained by the different age structures of the studied populations, different access to healthcare services in Russian regions, and different methods for diabetes prevalence estimates.
According to the WHO STEPwise approach to surveillance (STEPS) (2019), raised fasting blood glucose (≥7.0 mmol/L) or under medication for raised blood glucose was found in 7.1% of the Ukrainian population: 6.7% of men and 7.4% of women (18–69 years old). Nearly half of them had not previously been diagnosed with diabetes.24 The percentage of population with diabetes is lower in Belarus (3.2 of men and 3.9 of women) and higher in the Republic of Moldova (11.5 of men and 13.0 of women); however, in all three countries the prevalence of diabetes in women is higher than in men.25 The higher prevalence of diabetes in women than men observed in KYH is the opposite pattern to that observed in Norway and most other countries where the majority of the population are of European ancestry. The higher diabetes prevalence in men is usually explained by diverse biological, cultural, lifestyle, and environmental factors.26–29 Explanations for the pattern observed in Russia require further research. Certain cultural factors in Russia may be considered distal, that is, influencing behavior, and modify the biologically lower predisposition of women to develop diabetes.
Estimates of the prevalence of diabetes in Norway are available from national registries with prospectively collected data on prescriptions of antidiabetic drugs and diabetes diagnoses from hospitals and primary care visits for all residents in Norway aged 30–89 years. Crude prevalence of type 2 diabetes increased from 4.9% to 6.1% from 2009 to 2014, and diabetes prevalence was higher in men than in women (6.8% vs 5.3% in 2014).30 However, these estimates do not include undiagnosed diabetes cases that would be detected by screening. Intensive pharmacological and lifestyle management of diabetes delays onset and slows the progression of diabetes complications.31 32 Our study has shown that the proportion of undiagnosed diabetes is apparently smaller in the Norwegian study compared with the Russian study, but is still of significant public health concern given the potential health consequences of unmanaged diabetes.33
Weight reduction and diet modification interventions in people with impaired glucose tolerance reduced the incidence of diabetes in randomized controlled trials.34 35 Therefore, lifestyle interventions would be beneficial for both persons with clinically defined diabetes and persons with pre-diabetes.36 In our study prevalence of pre-diabetes was higher in KYH compared with Tromsø 7, which means there is much potential for diabetes prevention. Incorporation of a broader definition of pre-diabetes (HbA1c ≥5.7% or fasting glucose ≥5.6 mmol/L) to the diagnosis guidelines in Russia may be justified to prevent more cases of diabetes with timely intervention if the change in cut-points is shown to be cost-effective.
Our data do not explain in full why prevalence of diabetes differs in Norway and Russia particularly among men. Our measures of adiposity (BMI and WC) explained a substantial proportion of difference among women (46%), but these factors did not make an important contribution to differences among men. Interestingly, after accounting for adiposity the remaining difference in diabetes prevalence between KYH and Tromsø 7 study was similar for men and women (double the odds of diabetes prevalence). It was previously shown even among people of European ancestry that differences exist in the relationship between body fat and BMI.37 Also, the association of obesity and diabetes was shown to be stronger in low education groups, which suggests that socioeconomic circumstances may influence vulnerability to adiposity.38
It has been previously demonstrated that smoking is associated with diabetes, with a relative risk of 1.4 (adjusted for the baseline BMI).22 39 hsCRP reflects the level of general inflammation and is positively associated with obesity and diabetes.21 As the prevalence of smoking and hsCRP levels are higher among Russian men compared with men in Norway, we expected them to contribute to some of the difference in diabetes prevalence. However, we did not observe an additional contribution of these factors to explaining the differences in diabetes prevalence when adiposity measures were already included in the model. Among women, smoking and hsCRP made a small additional contribution to the difference in diabetes prevalence between studies after accounting for adiposity.
There are other potential explanations for the differences in diabetes prevalence between studies, such as diet,40 41 levels of physical activity,42 and sedentary behavior.43 Unfortunately, comparable data on these factors between our two studies are not available.
Type 2 diabetes is a multifactorial disease and involves genetic, behavioral and environmental factors, and their interaction.44 However, researchers still have a limited understanding of the genetic and epigenetic contribution to type 2 diabetes: only 10%–15% of heritability can be explained by known genetic variants.45 At the present time we do not have genomic data for both studies in order to investigate any differences between them.
Limitations
The major limitation of the mediation analysis in our study is the cross-sectional nature of the data. People who knew they had diabetes could have attempted to lose weight, increase physical activity, eat a healthier diet, and stop smoking. For example, lower LDL-cholesterol levels in participants with diabetes in Tromsø 7 study can in part be explained by higher use of lipid-lowering medications and changes in diet after diabetes diagnosis. Beyond this it is likely that our anthropometric measures of adiposity in the two populations failed to adequately capture differences in the extent of visceral abdominal adiposity, which is particularly strongly related to risk of diabetes.46 Validity of the mediation estimates is dependent on the assumption of no uncontrolled confounding for the exposure–outcome, exposure–mediator, or mediator-outcome relations.20
Although we were not able to distinguish between type 1 diabetes and type 2 diabetes in our study, our results will be principally driven by type 2 diabetes because it constitutes between 90% and 95% of all diabetes in these populations.4
Finally, care must be taken before generalizing the study findings to the populations of Russia and Norway as a whole. First, the studies were conducted in three cities whose characteristics will differ in some respects from the national populations. In addition there is the uncertainty about whether the participants we studied were representative of their own cities’ populations. The Tromsø 7 study had a good response rate (65%), as did the study in Arkhangelsk (68%), although in Novosibirsk the response rate was low (41%).14 The participants who did not attend the health check in KYH study were likely to have more adverse risk factor profile than those who did (online supplemental tables 2 and 3). However it is notable that our estimates of diabetes prevalence from KYH are consistent with those of other population-based studies in Russia. Similarly, prevalence estimates for diabetes in Tromsø 7 are similar to the study reporting diabetes prevalence in the whole of Norway. Potential explanatory (mediating) effects of specific biomedical markers are likely not to be affected.