This is the first study from the Central Asian region to investigate the epidemiology of Type 1 and Type 2 DM patients using a large-scale administrative health data in Kazakhstan. In this study, we described incidence, prevalence and survival in Type 1 and Type 2 DM patients who were registered in UNEHS from 2014 to 2019 in Kazakhstan and investigated demographical factors and DM-related complications associated with all-cause mortality.
We reported that the incidence and prevalence of Type 1 DM in 2019 was 17 and 152 per 100 000, respectively, which was in line with reported numbers of International Diabetes Federation (12). Recent meta-analysis by Mobasseri et al. also reported that the incidence of Type 1 diabetes in Asia, Africa, Europe, and America was 15 per 100 000, 8 per 100 000, 15 per 100 000 and 20 per 100, respectively. Also, the global prevalence of type 1 diabetes in the above regions was, 69 per 100 000, 35 per 100 000, and 122 per 100 000, respectively (13).
Our study reports the prevalence of Type 2 diabetes in 2019 of 2075 per 100 000 population. However, globally the prevalence of Type 2 diabetes estimated 6059 per 100 000, which was three times higher (14). This finding shows a significant underestimation of the prevalence of Type 2 DM in Kazakhstan. In fact, a previous study based on multistage cluster random sampling showed that the prevalence of Type 2 Diabetes was 8% among 4753 participants from four distinct regions of Kazakhstan. And the same study reported a total of 54% of newly diagnosed Type 2 Diabetes patients (4). Similar results were obtained from another study where authors reported the prevalence at 8.2% (95% CI 7.7%−8.6%) (5). These findings suggest that a large proportion of patients are undiagnosed and unregistered. However, the trend of increasing prevalence of Type 2 DM over the years is in line with global trend (16, 12). This trend can be partly explained by the rising life expectancy which may lead to increased prevalence of diabetes.
Mortality rate of Type 2 diabetes in our study was similar to WHO report 2016 which reports mortality rate 53.6 per 100 000 (15), while it was 55 per 100 000 in 2016 in Kazakhstan.
Diabetic neuropathy, nephropathy, retinopathy, diabetic foot and neoplasms were more common in Type 1 DM patients compared to Type 2 DM, while hypertension and coronary artery disease were more common in Type 2 DM patients compared to Type 1 DM.
Prevalence of coronary artery disease in our study was 18,7%, which was in line with global prevalence of 21% (12). However, we reported lower prevalence of stroke (2.5%) compared to global prevalence (7.6%) in diabetic patients (12). This might be due to undiagnosed and unregistered cases. Prevalence of diabetic retinopathy in Type 1 and Type 2 diabetes was 10,9% and 3,6%, respectively, which was within a wide range of global prevalence, 6.7% to 34.9% and 4.4% to 8.2%, respectively (12). Prevalence of diabetic foot in our study was 5,4% with 1% suffering from amputation. These findings are in line with global prevalence of diabetic foot of 6,4% and amputations of 1% (12). We reported a prevalence of diabetic nephropathy of 1.7% in Type 1 and Type 2 DM patients. However, the global prevalence of diabetic nephropathy is 30-50% (16). We may speculate that most cases registered in the database are advanced cases with end stage renal disease requiring dialysis. Nevertheless, the global prevalence of ESRD in patients with diabetes ranges from 19.0% in 2000 to 29.7% in 2015 worldwide (17). Therefore, we might underestimate the prevalence of diabetic nephropathy.
We have found a significantly higher mortality rate in men compared to women with diabetes, which was also reported in the Kazakhstani general population (18). Even though there is no data on men and women frequency of visits in Kazakhstan it might be that women comply to a larger extent than men with a doctor's advice. A Swedish study showed that women with diabetes attend outpatient clinics more frequently than men with diabetes. That would give the women a greater opportunity to control high blood pressure and cholesterol levels (19). The more frequent contact of women with health care in general may result in diabetes being diagnosed at an earlier and milder stage in women than in men, resulting in higher survival.
In contrast, Italian study reported the opposite findings of females having a higher risk of all-cause mortality than men (IRR 1.77; 95% CI 1.64–1.92) (18). The authors explain this by the fact that females with diabetes have higher prevalent abdominal obesity, increasing the risk of hypertension and a worse lipid profile. The authors also reported that increased age is associated with increased risk of all-cause mortality in patients with diabetes (20). This was in line with our findings.
Coronary artery disease, diabetic nephropathy, stroke, amputations and neoplasms were associated with a higher risk of all-cause death in patients with Type 1 and Type 2 DM. Diabetic neuropathy, hypertension, and diabetic retinopathy were associated with a lower risk of all-cause mortality in patients with Type 1 and Type 2 DM.
In the present study, non-hypertensive patients are at increased risk of all-cause mortality suggesting a paradoxical protective effect of elevated blood pressure in patients with Type 1 and Type 2 DM. This observation disagrees with the high risk of death conferred by elevated blood pressure in the general population. The apparent paradoxical protection afforded by elevated blood pressure against mortality observed in the present study can be partly explained by the phenomenon of reverse epidemiology of traditional risk factors reported in chronic conditions such as chronic kidney disease and dialysis, chronic heart failure, cancer and chronic infections like HIV/AIDS (21,22). This inverse relationship seems to indicate the existence of additional and more significant risk factors such as malnutrition and inflammation which might alter the relationship between traditional risk factors and outcomes in patients with diabetes (21,22). Another plausible explanation of the apparent paradox can be due to selection by indication. Registered hypertensive patients might be better protected and have a better track from healthcare professionals. Moreover, they may receive more intense medical care, including pharmacological therapy that may explain this association. However, data on medication was not available, so we could not explore this association.
The present study has several strengths. First, to our knowledge this is the first study from the Central Asian region to demonstrate the epidemiology of Type 1 and Type 2 DM patients based on a compiled nationwide digital healthcare data from Kazakhstan. Second, the data was linked to the Population Registry to determine the outcome data (died or alive).
Our study has a few limitations including the reliance on secondary data, which in turn is affected by the accuracy of measurement. Another main limitation is lack of data on treatments and clinical and laboratory data (blood pressure, HbA1c, cholesterol, etc.). Fair to mention also that in the current study the lack of cause-specific mortality data, possible errors with disease coding, and potential loss of follow-up for patients who might left the country could affect the results. And, residual confounding is likely present in the study results as the registry data was limited to few covariates to be adjusted for.