PDF           PRINT VERSION      Аннотация (Рус.)    Корутунду (Кырг.)    Comments      

Marina S. Moldobaeva, Anastasiya V. Vinogradova, Marina K. Esenamanova* , Bahtygul S. Zhalilova, Gulzat K. Sharshenalieva, Dinara I. Isabaeva

Department of Propedeutic Therapy with Course on Endocrinology and *Department of Hygienic Disciplines, Kyrgyz State Medical Academy named after I.K. Akhunbaev, Bishkek, Kyrgyzstan

Abstract

Objective: In  diabetes  mellitus (DM) type 2, there  is  a  very  high  risk  of developing cardiovascular  (CV) events.  We aimed to study the total CV risk of the indigenous people of  Kyrgyzstan with  impaired carbohydrate metabolism (DM type 2 and impaired glucose tolerance, IGT), depending on  the region of residence (low and high altitudes), and to  develop targeted preventive measures.

Methods: Overall, 248 families (992 people) in the Naryn (high-altitude) (study group) and 260 families (1041 people) in the Chui region (low-altitude) (control group) were surveyed and  363 people with DM type 2 and IGT were identified, of which: 138 people in the study group and 225 people in the control group.

Results: In patients with DM type 2 and IGT, moderate CV risk was found in the low-altitude and high-altitude in men and women aged 46–65 years, the  leading risk factor in men is BMI>25 kg/m²; in women, hypertension (HT)  and hypercholesterolemia. A high risk of  CV  complications was detected only in the low-altitude in men aged 46–65 years, the leading risk factor is HT. High and very high risk of CV complications  are rarely found both in the low-altitude and in the high-altitude.

Conclusion: During stratification of total CV risk, 363 people with carbohydrate metabolism disorders (DM type 2 and IGT) of  2033 native population living in 2  regions  of Kyrgyzstan revealed features of the total CV risk: BMI>25kg/m² for men of  high- altitude  and  low-altitude,  HT  and hypercholesterolemia  for  women of high-altitude, and for men, low-altitude only HT. Both in the high-altitude and in the low-altitude, low and moderate CV risk are predominantly expressed, and high and very high CV risk are rare.

Key words: diabetes mellitus, impaired glucose tolerance, native population, low-altitude, high-altitude, factors of total cardiovascular risk

Introduction

In diabetes mellitus (DM) type  2, a very high total cardiovascular (CV) risk  of development and mortality from coronary  artery  disease (CAD) is  by 2–4 times and acute myocardial infarction -  by 6– 10 times  higher than in the general population (1-8). In Kyrgyzstan in 2015, the number of deaths from DM at the age of 20-79 years was 2560.3 (in the world  -  4960535.8)  (9),  in 2017  -  2482.9 (in the world 3990420.6), including from cardiovascular (43% of cases) and cerebrovascular (12%) pathology  (10,11). For comparison, in Russia, these figures were 55-60% and 29% for CV and cerebrovascular pathology, respectively (12-15).  Since DM type 2 is an independent  risk factor of CV disease (16), the  study of the total CV risk  in DM is important (17-18). Risk factors can be modified by preventive measures and influence course of diseases, including diabetes (19).

The carbohydrate metabolism in highlanders has specific  features: in high-altitude, the incidence of diabetes and average blood glucose levels are lower (7). Obesity, like DM type 2, hypertension (HT) and  atherosclerosis, among the high-altitude of all age groups is 3 times less common than among the population of the low-altitude (20).

The  standardized  mortality rate  from circulatory diseases aged up to 65 years and  older  per  100,000 population (WHO,  2016)  in Kyrgyzstan is  high with a tendency  to  decrease:  from 714.1 (2009)  to  658.73 (2013);  in Germany from 217.16  (2009)  to  186.28 (2014);  in Kazakhstan from 626.37 (2009)  to 305.09(2014), in Russia from 682.98 (2009) to 613.31 (2011). Standardized mortality rate from CAD in Kyrgyzstan is also high with a similar tendency to decrease from 437.78 (2009) to 429.36 (2013); in Germany from 84.43  (2009) to 68.88 (2014); in Kazakhstan from 238.5 ( 2009) to 112.37 (2014); in  Russia from 351.72 (2009) to 323.25 (2011).  Standardized mortality rate from concurrent  cerebrovascular diseases in  Kyrgyzstan is  high with a tendency to decrease from 234.13 (2009) to 175.43 (2013); in Germany from 37.62  (2009) to 30.07 (2014); in Kazakhstan from 180.41 (2009) to 113.81 (2014); in Russia from 220.67 (2009) to 187.0 (2011) (22).

 In Kyrgyzstan, in the structure of causes of mortality of the population, circulatory system diseases take the leading places, although a slight decrease is observed: in general, this indicator was 50.5% (2013) and 50.4% (2014), 50.8% (2015), 50.8% (2016), including in Chui - 54.2% (2013), 53.7% (2014), 54.4% (2015) and 52.8% (2016) in Naryn - 42.7% (2013), 42.4% (2014), 42.0% (2015) and 44.6% (2016) regions (23-25).

The incidence of CV disease, including diabetes, is increasing in   Kyrgyzstan: if  in 2008 there were 28,694 patients (783.3 per 100 thousand),  then in 2014 there  were 46,468 (1157.0 per 100 thousand) patients  with diabetes and its  prevalence at  the age of  20–79 years  in Kyrgyzstan is  5.2 (3.7– 10.4).  An increase in the number of patients with diabetes  is  also noted by region: 7580 people in Chui (1230.1) and Naryn-2032 (1130,0) regions (23-25). Research has shown that  among risk factors,  HT  among residents  of the Chui region was registered in 34.1% of respondents, higher in women than in men (36.7 vs. 30.5%,  95% CI 0.01–0, 11; p=0.021). With age, there was a regular increase in the prevalence of HT, reaching in the age group of 60 years and over - 75.2%, however, the following pattern is revealed: at the age of 40 years, the prevalence of  HT is  somewhat higher in men, and after 50 years the incidence of elevated blood pressure prevails in women (26).

 If we compare the data of our previous studies, where the prevailing risk factors  of development  of  diabetes,  irrespective  of  the  region  of  residence and    sex were irregular  consumption of  vegetables  and  fruits, visceral obesity and overweight, the factors of total CV risk among native population of Kyrgyzstan with DM type 2  and    IGT  are not well established (21).

According to the data of Mashalayeva et al. (27), the most common risk factors of CAD among the surveyed residents of the low-altitude and high-altitude regions of Kyrgyzstan are HT (82% and 69.49%) with the significantly higher levels of systolic  (145.17±13.89 mm Hg  vs 131.6±15.9 mm Hg, respectively), and diastolic  (90.25±4.77 mm Hg vs 84.72±7.97 mm Hg) blood pressure levels in the residents of high-altitude compared with the low-altitude (p<0.05); then smoking (62% and 52.4%) and obesity (53% and 44.91%) (33.6±5.02 kg/m² vs 28.1±3.18 kg/m², p <0.05).

Systematic coronary risk evaluation (SCORE) allows to determine 10-year risk of fatal cardiovascular events in adult population (28, 29). Total CV risk assessment is recommended in presence of risk factors, including diabetes (29). Several studies described value of SCORE in prediction of 10-year CV events in different populations (30, 31).

In Kyrgyzstan at various mountain levels, where mainly native population lives and works, the course of diabetes and the development of CV complications can be modified.

However, there are no studies on total CV risk assessment using SCORE in populations of low and high altitudes with DM type 2 and IGT.

Thus, there is a need to study the total  CV risk  among the native  population of  Kyrgyzstan,  depending on the altitude of  the region of residence and gender to control the 10-year risk of death from CV  disease in patients with DM type 2.

 We aimed to study the total CV risk of the indigenous people of Kyrgyzstan with impaired carbohydrate metabolism (DM type 2 and IGT), depending on the altitude (high and low altitude) of the region of residence, and to develop targeted preventive measures.

Methods

A total of 248 families  (992 people)  in the high-altitude Naryn (study group)  and  260 families  (1041 people) in the low-altitude Chui region (control group) were examined. Of these, 363 people with DM type  2 and  IGT were identified, of them: 138 people in the study group, 10 people with diabetes, 128 people with IGT, and 225 people in the control group, 54 people with diabetes and with IGT - 171 people. We also divided participants by age groups: 18-45 years old, 46-65 years old and over 65 years old.

The study was approved by the bioethics committee of the Kyrgyz State Medical Academy. Before   the survey, we obtained personal informed consent from each participant. The study was conducted in compliance with Helsinki declaration 2013.

The altitude of 1500 - 3500 m (International Society for Mountain Medicine) is attributed to the high-altitude. The high-altitude Naryn region, where the native population  was  surveyed  is  located  at  an  altitude  of  2040-3500  m,  the  low-mountain Chui region is  located  at  an altitude of 500-1500 m above sea level (32-34).

Randomization was performed according to the number of families and the number of patients examined.

The smokers were people who  smoked at least one cigarette per day, with gradations: never smoked, smoked in  the past, smoke now.

Overweight and obesity were defined by the formula of body mass index (BMI) = weight (kg) / height (m²), according to BMI: overweight—BMI: 25–29.9kg/m², and  obesity—BMI: ≥30kg/m². A diagnosis of abdominal or  central obesity was established if  waist circumference  was >94cm in men and >80cm in women ( 35).

Blood pressure was measured by a standard method,  and  hypertension was established if  blood pressure  of ≥140/90 mm Hg (36).

The total cholesterol (mmol/l) level in  serum was  determined by photocalorimetric  method and  the level of glucose concentration in capillary blood was determined by the express method  using a glucometer (Fine test).

Diagnostic criteria for diabetes:  whole capillary blood:  fasting  glucose ≥6.1 mmol/L , two-hour blood glucose ≥11.1 mmol/L following  a 75g oral glucose load;  impaired  glucose tolerance (IGT) diagnostic criteria, whole capillary blood :  fasting  glucose < 6.1 mmol/L;  two-hour blood glucose  ≥ 7.8 and  <11.1 mmol/L  following  a 75g oral glucose load (10, 18).

The total CV risk was  determined  using the SCORE (Systematic Coronary  Risk Evaluation) scale, the European model which determines the 10-year total  CV risk  of all events. The degree of total  CV risk : very high risk –≥10%, high risk -> 5% and <10%, moderate risk -> 1% and <5%, low risk -< 1% (28, 29).

Statistical analysis was performed by using Medstatistic and Graphpad softwares. We used descriptive statistics to present categorical variables, Fisher exact and Chi-square tests to compare proportions, and Spearman ρho correlation analysis to estimate the association of  score components with altitude, age, and sex. Odds ratios with 95% confidence intervals were also calculated.

Results

 Of  the  992  native-population  of  the  high-altitude  Naryn  region of Kyrgyzstan, 14.91% and of 1041 people of the low-altitude Chui region, 26.8%  had diabetes or IGT. Among  risk factors of  CV risk   in the  native population  of  Kyrgyzstan  with  DM type 2 or IGT,  in the high-altitude group in men, BMI prevails>25 kg/m², in women hypercholesterolemia varies from 4.1 to 4.5 mmol/l; in the low-altitude group in men, high blood pressure  predominates, in women, BMI>25 kg/m ² (see Table 1). Comparison of high and low altitude groups showed higher blood pressure levels and cholesterol levels (4.1-4.5 mmol/l) in men and women of low altitudes as compared to  men and women of high altitudes (p<0.001 and p<0.001).

Table 1. Prevalence rates of cardiovascular risk factors among native population of Kyrgyzstan with impaired carbohydrate metabolism (DM or IGT), depending on the region of residence (high and low-altitude regions) and gender (%)
	Men, n(%)				Women, n(%)
	High-altitude	Low-altitude	p		High-altitude	Low-altitude	p
BMI>25 kg/m2	19 (43.6)	47 (51.62)	>0.05		41 (43.6)	94 (70.12)	>0.05
BP≥140/90 mmHg	10 (22.72)	49 (53.83)	systolic	<0.02	16 (17.01)	59 (44.02)	systolic	>0.05
			diastolic	<0.001			diastolic	<0.001
Cholesterol 4.1-4.5 mmol/l	18 (40.2)	42 (46.14)	<0.001		49 (52.12)	69 (51.48)	<0.001
Cholesterol >4.5 mmol/l	7 (15.9)	30 (32.95)	>0.05		8 (8.5)	22 (16.41)	>0.05

                                                                                          

Table 2. Age- and sex-dependent distribution of demographic, anthropometric data and risk factors in native population of high and low altitudes
Criteria	Men, n (%)		Women, n (%)
	Low-altitude	High-altitude	Low-altitude	High-altitude
Age 18-45 46-65 > 65 years
	11 (12.08)	34(77.27)	22 (16.41)	36 (38.30)
	71 (78.03)	10(22.72)	104 (77.61)	57 (60.64)
	9(9.89)		8(5.98)	1(1.06)
BMI, kg/m2  <25 kg/m2 18-45 46-65 > 65 years			а	b
	9 (9.89)	20(45.45)	14 (10.44)	33(35.11)
	32 (35.16)	5(11.36)	22(16.41)	20(21.27)
	3 (3.29)		4 (2.98)
25-29.9, kg/m2 18-45 46-65 > 65 years	c	d
	2(2.19)	10(22.72)	6 (4.47)	3(3.19)
	23(25.27)	2(4.54)	32 (23.88)	17(18.08)
	3(3.29)		3 (2.23)
>30 kg/m2 18-45 46-65 > 65 years
		4(9.09)	2 (1.49)
	16 (17.58)	3(6.81)	50 (37.31)	20(21.27)
	3(3.29)		1 (0.74)	1(1.06)
Blood pressure <140/90, mmHg 18-45 46-65 > 65 years
	9(9.89)	28(63.63)	21 (15.67)	35(37.23)
	28 (30.76)	6(13.63)	52 (38.81)	43(45.74)
	5(5.49)		2 (1.49)
≥140/90,mmHg 18-45 46-65 > 65 years
	2 (2.19)e	6(13.63)	1 (0.74)	1(1.06)h
	43 (47.25) f	4(9.09)	52 (38.81)	14(14.89)i
	4 (4.39)g		6 (4.47)	1(1.06) j
Smokers: 18-45 46-65 >65 years
	1 (1.09)	10(22.72)		17(18.08)
	32 (35.16)	3(6.81)	1(0.74)	1(1.06)
	4 (4.39)
Non-smokers 18-45 46-65 > 65 years
	10 (10.98)	24(54.54)	22 (16.41)	19(20.21)
	39 (42.85)	7(15.91)	103 (76.86)	56(59.57)
	5(5.49)		8 (5.97)	1(1.06)
DM type 2 18-45 46-65 > 65 years
		4(9.09)		1(1.06)
	19(20.87)	1(2.27)	26(19.41)	4(4.25)
	6(6.59)		3(2.23)
IGT 18-45 46-65 >65 years
	11(12,08)	30(68.18)	22(16.41)	35(37.23)
	52(57.14)	9(20.45)	78(58.21)	53(56.38)
	3(3.29)		5(3.73)	1(1.06)
Cholesterol<4 mmol/l 18-45 46-65 > 65 years
	1(1.09)	18(40.91)	10(7.46)	19(20.21)
	18(19.78)	1(2.27)	32(23.88)	18(19.15)
			1(0.74)

 

Cholesterol 4.1-4.5 mmol/l 18-45 46-65 >65 years
	10(10.98)	12(27.27)	11(8.21)	16(17.02)k
	25(27.47)	6(13.63)	54(40.29)	32(34.04)l
	7(7.69)		4(2.98)	1(1.06)m
Cholesterol  >4.5mmol/l 18-46 46-65 >65 years
		4(9.09)	1(0.74)	1(1.06)
	28(30.76)	3(6.81)	18(13.43)	7(7.44)
	2(2.19)		3(2.24)
Cardiovascular risk Low <1% 18-45 46-65 >65 years
	11(12.08)	30(68.18)	22 (16.41)	36(38.29)
	30 (32.96)	5(11.36)	96 (71.64)	55(58.51)
	2 (2.19)		5(3.73)	1(1.06)
Moderate risk >1-<5% 18-45 46-65 >65 years
		4(9.09)
	17 (18.68)	2(5.49)	5 (3.73)	1(1.06)
	5(5.49)		1 (0.74)
High risk >5-<10% 18-45 46-65 >65 years
	13 (14.28)		2 (1.49)	1(1.06)
			1 (0.74)
Very high risk>10% 18-45 46-65 > 65 years
	11 (12.08)	3(6.81)	1 (0.74)
	2(2.19)		1(0.74)
1) p<0.05 BMI<25 kg /m2 in women of low-altitude and high-altitude, a, b OR is equal to 3.038 (CI95% 1.752-5.268). 2) p<0.05  BMI>25 kg/m2  in men of low-altitude and high-altitude, c, d OR is 0.711 (CI 95% 0.345-1.468). 3) p<0.001 BP above 140/90 in low-altitude men aged 46–65 years compared with other ages e,g, OR is 0.093 (CI 95% 0.020-0.428). 4) p<0.001 above 140/90 mm Hg in low-altitude women aged 46–65 years with other ages h, j, OR is equal to 3.286 (CI 95% 1,297-8,322). 5) p<0.001 cholesterol>4.1 mmol/l in women of high-altitude aged 46-65 years with other ages k, m, OR is equal to 2.287 (CI 95% 0.975-5.367).

Anthropometric indicators, depending on sex,  age and region of residence (Table 2), show a BMI of <25kg/m² detected more often in population of  high-altitude (for women, p<0.05). Overweight / obesity (BMI> 25kg/m²) is more common in low-altitude men (51.62%) than in high-altitude men (43.16%) (p<0.05).

In the high-altitude,  BP ≥140/90 mm Hg prevails in women aged 46–65 years (14.89%) (p<0.001), and in low-altitude in men aged 46–65 years (47.25%) (p<0.001).

In the high-altitude, mostly men aged 18–45 years (22.72%) smoke, and in the low-altitude, mostly men aged 46–65 years (35.16%) are smokers. In the high-altitude, diabetes was first detected only in 11.36% of men and in 5.31% of women aged 18–65 years, and in the low-altitude DM type 2 prevails between the ages of 46-65 years in 20.87% of men and in 19.41% of women. IGT prevails in 68.18% of men aged 18–45 years in the high-altitude, and in 58.21% of women aged 46–65 years in the low-altitude. Cholesterol >4.1-4.5 mmol /l prevails in women (p <0.001) in the age group 46-65 years in both altitudes, however being significantly lower in women residing in high altitudes as compared to low altitudes (p<0.05).

High risk of CV complications was detected in low-altitude in 13 (14.28%) men aged 46-65 years old, the leading risk factors are: HT and hypercholesterolemia in 84.61% and BMI>25 kg/m² in 46.15%, and in 7 of them there is a combination of 3 risk factors  and in 4 men -2 risk factors.

A high risk of  CV complications was found in low-altitude in 2 (1.49%) women aged 46-65 years old, the leading risk factors are: BMI> 25 kg/m², hypercholesterolemia in 100% and HT in 50%, and 1 of them has a combination of 3 risk factors and 1 woman -2 risk factors; in the high-altitude, only 1 (1.06%) woman  aged 46–65 years has high risk , and there is a combination of -3 risk factors. Very high  risk of CV complications was  found in low-altitude in 11 (12.08%) men aged 46–65 years,  in high-altitude in 3 (6.81%)  and  in women in low-altitude in 1 (0.74%) women aged 46 -65 years, and there is no very high risk  in the high-altitude women (p> 0.05).

 With the stratification of the total CV risk, low risk  is more pronounced in the high- altitude and moderate risk prevails in low-altitude men and women(Table 3).

Table 3. Stratification of total cardiovascular risk depending on the region of residence and gender

Low risk

Moderate risk

High risk

Very high risk

High-altitude

Low-altitude

High-altitude

Low-altitude

High-altitude

Low-altitude

High-altitude

Low-altitude

M, %

W, %

М, %

W, %

М, %

W, %

М, %

W, %

М, %

W, %

М, %

W, %

М, %

W, %

М, %

W, %

79.55

97.86

47.23

91.78

14.58

0.06

24.17

4.47

-

1.06

14.28

2.23

6.81

-

14.27

1.48

Discussion

Despite the fact that patients with DM type 2 are categorized as high/very high total CV risk, hyperglycemia is an independent  risk factor of CV complications and their risk stratification is justified because their timely detection contributes to a significant reduction in overall and CV mortality.

Previously,  we studied the significance of the risk factors  and the stratification of the 10-year risk of developing  DM type 2 in native population of the Chui and Naryn regions of Kyrgyzstan. The following features  were identified: low risk prevails  in both women and men, high risk in 4.6% of women and 2.1% of men in the Chui region and in 1.4% of women and 1% of men in the Naryn region, regardless of gender, and a very high risk does not occur (21). Different mountain levels of Kyrgyzstan, where mostly native population live and work, can modify the course of  DM type  2 and the development of the CV complications. Of  the 992   native population of the high-altitude Naryn region of Kyrgyzstan, 14.91%  and  of  1041  people  of  the  low-altitude  Chui  region,  26.8%  revealed impairment of carbohydrate metabolism in form of DM type 2 and IGT.

For the first time in Kyrgyzstan, we identified  the components of the total CV risk  in these patients:  BMI <25kg /m² was detected more  often in native women of high-altitude than low-altitude (OR 3.038, CI 95% 1.752-5.268), BMI>25kg/m² was more characteristic for low-altitude men than the high-altitude men (OR 0.711, CI 95% 0.345-1.468), in the high-altitude the HT prevails in women (OR 3.286, CI 95% 1,297-8,322), and in the low-altitudes in men aged 46-65 years (OR 0.093, CI 95%  0.020-0.428);  in  the  high-altitude,  there is a tendency of cholesterol >4.1 mmol/l prevailing  in women in the 46–65 age group, though insignificantly (OR 2.287, CI 95% 0.975-5.367).

Moderate CV risk was found in low-altitude  and high-altitude in men aged 46–65 years; the leading risk factor was BMI>25kg/m². When studying the linear relationship between risk ratios and leading risk factors (ρ), there is a close relationship between very high CV risk in men in the low-altitude  at the age of 46–65 years old with HT  (ρ = 0.673, (p <0.05) and in men in the high-altitude age 46-65 years old with a BMI>25 kg/m² (ρ = 0.500, p <0.05).

Moderate CV risk was found in the low-altitude and high-altitude women aged 46-65 years, the leading risk factors  are: hypertension and hypercholesterolemia. A high risk of CV complications was detected only in the low-altitude in men aged 46–65 years, the leading risk factor is HT. High and very high risks of CV complications are rarely found both in the low-altitude and high-altitude.

Conclusion

In the Kyrgyz population, when studying the 10-year total CV risk in patients with impaired carbohydrate metabolism (DM type 2 and IGT), the leading risk factors-components of the total CV risk  were revealed: overweight (BMI> 25 kg/m²) in men of low-altitude and high-altitude, HT and hypercholesterolemia in women of high-altitude, and in men of low-altitude only HT. Both in the high-altitude and in the low-altitude, low and moderate CV risk are predominantly expressed, and high and very high  CV risk are rare. First of all, men of both high-altitude and  low-altitude  need to be targeted for fighting BMI, then with HT, and for women with HT and hypercholesterolemia, it is necessary to monitor adherence to CV risk prophylaxis measures, first of all, adherence to diet and antihypertensive therapy.

Peer-review: External and internal

Conflict of interest: None to declare

Authorship: M.S. M., A.V. V., M.K. E. , B.S.Zh.,

G.K.Sh., D.I.I. equally contributed the study and preparation of manuscript

Acknowledgments and funding:

The  authors  would  like  to  thank  their  colleagues  who  helped  with  survey organization in Naryn and Chu regions: Naryn region- Dr. K.K. Kydyraliev; Chu region—Dr. G.K. Sharsehnalieva, Dr. D.I. Isabaeva,   Dr. Ch. A. Muratova and R.M. Attocurova.

Author Disclosure:

The survey and material collection was performed in the frame of the Help Age International project with the support of the European Union. The authors had no personal financial/material support for this study.