Risk of Type 2 Diabetes Mellitus Development in the Native Population of Low- and High-Altitude Regions of Kyrgyzstan: Finnish Diabetes Risc Score Questionnaire Results

Abstract

Moldobaeva, Marina S., Anastasiya V. Vinogradova, and Marina K. Esenamanova. Risk of type 2 diabetes mellitus development in the native population of low- and high-altitude regions of Kyrgyzstan: Finnish Diabetes Risc Score questionnaire results. High Alt Med Biol. 18:428–435, 2017.

Objective:

The number of patients with diabetes is steadily growing, but likely only half of all cases are ever identified. The Kyrgyz, native inhabitants of Central Asia, live in the mountainous area and have a particular lifestyle and nutrition. However, the risk of type 2 diabetes mellitus (T2DM) in our population is not well defined. Therefore, we aimed at determining the risk of T2DM development in the Kyrgyz population residing in low- and high-altitude (HAlt) regions by using the Finnish Diabetes Risc Score (FINDRISC) questionnaire.

Methods:

We included in the study 3190 randomly selected participants, including 1780 low-altitude (LAlt) residents (Chu region, 500–1200 m) and 1410 HAlt residents (Naryn region, 2000–4500 m), among whom there were 1207 men and 1983 women. Assessment of T2DM development was conducted by using the FINDRISC questionnaire and risk stratification was performed by region of residency, gender, and age.

Results:

An irregular intake of vegetables and fruits, increased waist circumference (WC), and increased body mass index (BMI) were identified as leading risk factors of T2DM development in native residents of Chu and Naryn regions of Kyrgyzstan. The 10-year risk stratification of T2DM development revealed the absence of a very high-risk group; high-risk status was more frequently identified among residents of the LAlt Chu district (4.7% of women and 2.1% of men), as compared with the HAlt population (1.9% of women and 1% of men) (p = 0.0018 for women and p = 0.09 for men).

Conclusions:

In the Kyrgyz population, a 10-year high risk of T2DM development is greater among residents of LAlts as compared with HAlts, irrespective of gender. No very high-risk group was detected in residents of low or HAlts. The leading composites of FINDRISC score are increased WC and BMI, possibly due to irregular intake of vegetables and fruits that are dependent on the altitude of residence and age.

Introduction

The number of patients with type 2 diabetes mellitus (T2DM) is steadily increasing. Its incidence is high in low- and middle-income countries (International Diabetes Foundation, 2015; WHO, 2016), with >70% of patients living in developing countries (Butler et al., 1985; Chiu, 2011; International Diabetes Foundation, 2015). In 2015, in Kyrgyzstan, the number of adults with undiagnosed T2DM was 97,400, and 25,603 patients died (International Diabetes Foundation, 2015). The prevalence of T2DM in 2014 in the high-altitude (HAlt) region (2000–4500 m) Naryn district was 1130.0 per 100,000 population and in the low-altitude (LAlt) (500–1200 m) Chu district it was 1230.0 per 100,000 population (Mirrakhimov and Meymanaliyev, 1992). Every other case of T2DM worldwide is not identified (International Diabetes Foundation, 2015), necessitating early identification of its risk factors.

Asymptomatic hyperglycemia is a significant risk factor for death from ischemic heart disease, especially in women (Gans and Donker, 1991; Barrett-Connor, 1997; Pyorala et al., 1997; Balkou et al., 1998). Cardiovascular complications are identified in 20%–30% of patients with newly diagnosed T2DM (Hansson et al., 1998; American Diabetes Association et al., 1999; Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, 2003; Zimmet et al., 2003; Mendis et al., 2011; Eckel and Cornier, 2014; American Diabetes Association, 2015).

About three quarters of the territory of Kyrgyzstan is mountainous (Mirrakhimov and Meymanaliyev, 1992), where a number of unfavorable factors, mainly hypoxia, affect health (West et al., 1983; Mirrakhimov and Meymanaliyev, 1992; de Mol et al., 2014). Residents of mountainous areas have lower levels of blood glucose as compared with lowland inhabitants (Srivastava et al., 1975; Castillo et al., 2007). Diaz et al. (1978) did not report any case of T2DM in residents of HAlt (>3000 m). Several studies (Woolcott et al., 2014; Xu et al., 2015) revealed an inverse association between incidence of T2DM and altitude. However, recent studies in Peruvian and Tibetan populations have demonstrated a high incidence of T2DM and glucose intolerance in residents of HAlt (>3500 m), possibly due to urban lifestyle changes and obesity (Bernabe-Ortiz et al., 2016; Okumiya et al., 2016).

There are racial differences in incidence and characteristics of T2DM. The inhabitants of the Southern Asia of Asian origin have higher insulin resistance, better functional activity of β cells (homeostasis model assessment of beta-cell function [HOMA-β]) than patients with T2DM of Afro-Caribbean origin (Banerji et al., 1999; UK Prospective Diabetes Study Group, 1994; Webb et al., 1999; Corella et al., 2006; Nightingale et al., 2013). T2DM develops at lower ranges of body mass index (BMI) in the population of South Asia as compared with Caucasians from Europe (Petersen et al., 2006; Nightingale et al., 2013), justifying the necessity of using different BMI values in determining the risk of T2DM in Asians. Genetic studies also demonstrated that Asians are more susceptible to T2DM as compared with Europeans (Banerji et al., 1999; Goldstein and Scalia, 2004; Sniderman, 2007; Chiu, 2011; Indulekha et al., 2011; Kodama et al., 2013).

Thus, increase in the number of diabetic patients in Kyrgyzstan, absence of studies on risk factors of its development, and factors that might influence T2DM development such as altitude, obesity, and racial and genetic differences justify the study on its risk in the Kyrgyz population.

Among tools used for the screening of T2DM risk, Finnish Diabetes Risc Score (FINDRISC) has been validated in different populations and found useful in the prediction of incident diabetes development over 9-year follow-up in the United States population (Kulkarni et al., 2017); it was also accurate in the screening of undiagnosed T2DM, confirmed by fasting plasma/glucose tolerance test, HbA1c level in German, Philippines, Slovenian, Spanish, and Norway populations (Li et al., 2009; Ku and Kegels, 2013; Jolle et al., 2016; Salinero-Fort et al., 2016; Stiglic et al., 2016).

The aim of our study was to define the risk of T2DM development in native residents of the Kyrgyz Republic adjusted by age, sex, and altitude of residence—high (Naryn region—2000–4500 m) and low (Chu region—500–1200 m) altitudes using the FINDRISC score.

Methods

We performed a one-stage simple random sampling area selection to study the differences in the risk of T2DM in native residents of Halt and LAlt of the Kyrgyz Republic. We randomly selected villages from two districts: LAlt (500–1200 m) Chui district and HAlt (2000–4500 m, mountainous region with peaks 4500 m and narrow valleys—2000–2500 m) Naryn district. Overall, 90% of families took part in the survey—3190 native Kyrgyz residents, including 1780 residents from LAlt Chu and 1410 residents from HAlt Naryn; among them, there were 1207 men and 1983 women. Altitude levels were defined according to standards accepted in our country (Mirrakhimov and Meymanaliyev, 1992). Stratification was carried out by region and sex. Patients with an established diagnosis of T2DM were excluded from the study.

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.

To assess the risk of T2DM development, we used the FINDRISC questionnaire: age (0 points: <45 years old, 2 points: 45–54 years, 3 points: 55–64 years, 4 points: >65 years old), BMI (0: <25 kg/m², 1 point: 25–30 kg/m², 2 points: >30 kg/m²), waist circumference (WC) (male/female—0 point: <94 cm/<80 cm, 3 points: 94–102 cm/80–88 cm, 4 points: >102 cm/>88 cm), physical activity (PhA) for a minimum of 30 minutes per day (3 hours per week) (0 points—yes, 2 points—no), regular intake of vegetables and fruits (0 point—every day, 1 point—not every day), regular intake of antihypertensive drugs (0 point—no, 2 points—yes), history of hyperglycemia during regular check-up, disease or pregnancy (0 points—no, 5 points—yes), and family history of diabetes (0 points—no, 3 points—yes in grandparents, aunt/uncle, cousins, 5 points—parents, brother/sister, child) (Lindstrom and Tuomilehto, 2003; Sorigure et al., 2012). The evaluation criteria for the risk stratification of T2DM were as follows: at least 7 points—low risk; 7–11 points—moderately elevated risk; 12–14 points—medium risk; 15–20 points—high risk; and more than 20 points—very high risk (Lindstrom and Tuomilehto, 2003; Sorigure et al., 2012).

Overweight and obesity were defined according to BMI: overweight—BMI: 25–29.9 kg/m², and obesity—BMI: >30 kg/m² (Alberti et al., 2006; Eckel and Cornier, 2014). A diagnosis of abdominal or central obesity was established if WC was >94 cm in men and >80 cm in women (Alberti et al., 2006). Low PhA was adopted in the absence of walking or physical exercise of at least 30 minutes per day (Lindstrom and Tuomilehto, 2003; Sorigure et al., 2012).

Statistical analysis was performed by using Medstatistic and Graphpad software. 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 FINDRISC score components with altitude, age, and sex.

Results

Risk factors of T2DM in residents of low and HAlts

Comparison of anthropometric data (Table 1) demonstrated higher prevalence of obesity among women (p = 0.0005) and men (p < 0.001) of LAlt as compared with residents of HAlt. Conversely, residents of HAlt more often had BMI <25 kg/m² as compared with their counterparts in LAlt (p = 0.01 for women and p = 0.0019 for men).

Table 1.

Age- and Sex-Dependent Distribution of Demographic and Anthropometric Data in Native Residents of High and Low Altitudes

	Female, n (%)		Male, n (%)
Variables	High-altitude Naryn	Low-altitude Chu	High-altitude Naryn	Low-altitude Chu
Age, years
<45	372 (48.6)	624 (51.7)	339 (52.6)	311 (55.1)
45–54	183 (23.9)	298 (24.5)	134 (20.8)	131 (23.2)
55–64	110 (14.4)	193 (15.8)	89 (13.8)	78 (13.8)
>64	100 (13.0)	101 (8.3)	83 (12.9)	44 (7.8)
Body mass index, kg/m²
<25, kg/m²
<45 years	212 (27.8)	336 (27.6)	263 (40.8)	208 (36.8)
45–54 years	67 (8.7)	66 (5.4)	58 (8.9)	51 (9)
55–64 years	25 (3.6)	31 (2.6)	44 (6.8)	26 (4.6)
>64 years	30 (3.9)	30 (2.4)	40 (6.2)	19 (3.4)
Total	334 (44)^a	463 (38)	405 (62.7)^b	304 (53.9)
25–29.9, kg/m²
<45 years	125 (16.3)	195 (16)	70 (10.8)	81 (14.4)
45–54 years	88 (11.5)	130 (10.7)	62 (9.6)	50 (8.9)
55–64 years	50 (6.5)	88 (7.3)	36 (5.6)	32 (5.7)
>64 years	34 (4.4)	46 (3.8)	34 (5.3)	18 (1.3)
Total	297 (38.7)	459 (37.8)	202 (31.3)	181 (32.2)
>30, kg/m²
<45 years	34 (4.5)	93 (7.7)	6 (0.9)	22 (3.9)
45–54 years	28 (3.6)	102 (8.5)	14 (2.1)	30 (5.3)
55–64 years	36 (4.6)	74 (6)	9 (1.5)	20 (3.5)
>64 years	36 (4.6)	25 (2)	9 (1.5)	7 (1.3)
Total	134 (17.3)	294 (24.2)^c	38 (6.0)	79 (14)^d
Waist circumference, cm
<80 cm for women; <94 cm for men
<45 years	181 (23.7)	191 (15.7)	281 (43.6)	227 (40.3)
45–54 years	35 (4.6)	17 (1.4)	70 (10.8)	52 (9.3)
55–64 years	16 (2.1)	8 (0.6)	39 (6.1)	18 (3.2)
>64 years	11 (1.4)	11 (0.9)	36 (5.6)	22 (3.9)
Total	243 (31.8)^e	127 (18.6)	426 (66.1)^f	319 (56.0)
80–88 cm for women; 94–102 for men
<45 years	70 (9.2)	146 (12)	44 (6.7)	54 (9.6)
45–54 years	38 (4.9)	49 (4)	34 (5.3)	28 (4.9)
55–64 years	20 (2.6)	14 (2.9)	28 (4.4)	27 (4.7)
>64 years	17 (2.2)	14 (2.9)	27 (4.2)	10 (1.7)
Total	145 (18.9)	229 (18.4)	133 (20.6)	119 (20.9)
>88 cm for women; >102 cm for men
<45 years	121 (15.8)	287 (23.6)	14 (2.4)	30 (5.3)
45–54 years	110 (14.4)	232 (19.1)	30 (4.6)	51 (9.0)
55–64 years	74 (9.7)	171 (14)	22 (3.5)	33 (5.9)
>64 years	72 (9.4)	76 (6.3)	20 (3.1)	12 (2.9)
Total	377 (9.3)	766 (63)^g	86 (13.3)	126 (4.4)^h

p = 0.0111 and ^bp = 0.0019, as compared with women and men of same age of low-altitude Chu, respectively.

p = 0.0005 and ^dp < 0.0001, as compared with women and men of same age of high-altitude Naryn, respectively.

p < 0.0001 and ^fp = 0.0007, as compared with women and men of same age of low-altitude Chu, respectively.

p < 0.0001and ^hp < 0.0001, as compared with women and men of same age of high-altitude Naryn, respectively.

Prevalence of overweight/obesity varied according to age and was more frequent in the population younger than 55 years. In Chu and Naryn, 62% and 56% of women, respectively, had BMI ≥25 kg/m². Among men, 46.2% in Chu and 37.3% in Naryn were overweight or obese. In both regions, there was a reduction in the prevalence of overweight and obesity with an increase in age (ρ = −1.000, p < 0.05 for women and ρ = −0.850, p < 0.05 for men).

Residents of LAlt had a higher prevalence of abdominal obesity, as compared with people of HAlt (p < 0.0001 for women and p < 0.0001 for men), whereas WC <80 cm was characteristic for women (p < 0.0001) and men (p = 0.0007) of HAlt as compared with those of LAlt. WC >80 cm was prevalent among women <55 years old (81.4% for Chu and 68.2% for Naryn). Abdominal obesity in women showed negative association with age (ρ = −1.000, p < 0.05 and ρ = −1.000, p < 0.05, for LAlt and HAlt, respectively). Among men, WC >94 cm was revealed in the male population of <45 years: 45.3% of the men in Chu (ρ = −0.400, p < 0.05) and 33.9% of the men in Naryn (ρ = −0.200, p < 0.05).

Analysis of lifestyle habits (Table 2) revealed that a significant proportion of women of older age (>64 years) residents of LAlt had low PhA (sedentary lifestyle) as compared with their counterparts at HAlt (p = 0.0012). An active lifestyle was characteristic for younger women (<55 years) in Chu (84.5%) and Naryn (87.6%). There was an association of reduced active lifestyle prevalence with increasing age in both regions (Chu—ρ = −1.000, p < 0.05 and Naryn—ρ = −0.950, p < 0.05). Overall, 88.3% of men in Chu and 89% of men in Naryn, mainly of age <55 years, had an active lifestyle, which decreased with age (ρ = −1.000, p < 0.05). A higher proportion of population residing in HAlt consumed less fruits and vegetables as compared with women (p = 0.0001) and men (p = 0.0001) of LAlt. Consumption of vegetables and fruits decreased with an increase in age (ρ = −1.000, p < 0.05 for women and ρ = −1.000, p < 0.05 for men).

Table 2.

Age- and Sex-Dependent Distribution of Lifestyle Habits, Intake of Antihypertensive Drugs, and Family History of Diabetes in Native Residents of High- and Low Altitudes—Finnish Diabetes Risc Score

	Female, n (%)		Male, n (%)
Variables	High-altitude Naryn	Low-altitude Chu	High-altitude Naryn	Low-altitude Chu
Physical activity
Yes
<45 years	361 (47.2)	571 (46.9)	332 (51.5)	284 (50.4)
45–54 years	163 (21.3)	253 (20.8)	123 (19)	118 (20.9)
55–64 years	90 (11.8)	157 (12.9)	72 (11.2)	66 (11.7)
>64 years	56 (7.3)	47 (3.9)^a	47 (7.3)	30 (5.3)
Total	670 (87.6)	1028 (84.5)	574 (89)	498 (88.3)
No
<45 years	11 (1.4)	53 (4.4)	7 (1.1)	27 4 (.7)
45–54 years	20 (2.7)	45 (3.7)	11 (1.7)	13 (2.3)
55–64 years	20 (2.7)	36 (2.9)	17 (2.6)	12 (2.2)
>64 years	44 (5.6)	54 (4.5)	36 (5.6)	14 (2.5)
Total	95 (12.4)	118 (15.5)	71 (11)	66 (11.7)
Regular consumption of fruits and vegetables
Yes
<45 years	2 (0.3)	303 (24.9)	2 (0.3)	162 (28.7)
45–54 years	2 (0.3)	119 (9.8)	3 (0.4)	68 (12)
55–64 years	1 (0.1)	87 (7.2)	2 (0.3)	31 (5.5)
>64 years	2 (0.3)	22 (1.8)	0 (0)	12 (2.2)
Total	7 (1)	531 (43.7)	7 (1)	273 (51.2)
No
<45 years	370 (48.4)	321 (26.4)	337 (52.3)	149 (26.4)
45–54 years	181 (23.5)	179 (14.8)	131 (20.3)	63 (11.2)
55–64 years	109 (14.3)	106 (8.7)	87 (13.5)	47 (8.3)
>64 years	98 (12)	79 (6.4)	83 (12.9)	32 (5.7)
Total	758 (99)^b	685 (56.3)	638 (99)^b	291 (48.8)
Intake of antihypertensive medications
Regular
<45 years	9 (1.2)	7 (0.6)	3 (0.4)	3 (0.5)
45–54 years	20 (2.6)	20 (1.6)	1 (0.2)	11 (1.9)
55–64 years	22 (2.9)	18 (1.5)	5 (0.8)	7 (1.3)
>64 years	26 (3.4)	21 (1.8)	15 (2.3)	5 (0.9)
Total	77 (10.1)^c	66 (5.5)	24 (3.7)	26 (4.6)
Family history of T2DM
No
<45 years	360 (47)	589 (48.4)	334 (51.8)	287 (50.9)
45–54 years	177 (23.2)	273 (22.4)	130 (20.1)	120 (21.3)
55–64 years	108 (14.1)	178 (14.9)	88 (13.6)	75 (13.3)
>64 years	97 (12.7)	96 (7.8)	82 (12.8)	42 (7.5)
Total	742 (97)^d	1136 (93.3)	634 (98.3)^e	524 (93)
Grandparents
<45 years	2 (0.3)	54 (0.4)	2 (0.3)	7 (1.3)
45–54 years	1 (0.1)	6 (0.1)	1 (0.2)	0 (0)
55–64 years	0 (0)	2 (0.2)	0 (0)	1 (0.2)
>64 years	0 (0)	1 (0.1)	0 (0)	0 (0)
Total	3 (0.4)	63 (5.54)^f	3 (0.5)	8 (1.5)
Parents
<45 years	10 (1.3)	30 (2.5)	3 (0.4)	17 (3)
45–54 years	5 (0.6)	19 (1.6)	3 (0.4)	11 (1.9)
55–64 years	2 (0.3)	13 (1.1)	1 (0.2)	2 (0.3)
>64 years	3 (0.4)	4 (0.3)	1 (0.2)	2 (0.3)
Total	20 (2.6)	66 (5.8)^g	8 (1.2)	32 (5.5)^h

p = 0.0012, as compared with women of same age of high-altitude Naryn.

p = 0.0001, as compared with women and men of same age of low-altitude Chu.

p = 0.0002, as compared with women of same age of low-altitude Chu.

p = 0.0004 and ^ep < 0.0001, as compared with women and men of same age of low-altitude Chu, respectively.

p < 0.0001, as compared with women of same age of high-altitude Naryn.

p = 0.003 and ^hp = 0.0002, as compared with women and men of same age of high-altitude Naryn, respectively.

Women of HAlt more often regularly used antihypertensive drugs as compared with women of LAlt (p = 0.0002), and intake of antihypertensive drugs was positively associated with age in both regions (LAlt—ρ = +0.800, p < 0.05 and HAlt—ρ = +1.000, p < 0.05). An increase in the intake of antihypertensive medicines with advanced age was also characteristic for men of Naryn (ρ = +0.800, p < 0.05), and a weaker association was present in men of Chu (ρ = +0.200, p < 0.05).

A family history of T2DM varied according to altitude and sex, with lower prevalence in residents of HAlt as compared with those of LAlt (p = 0.0004 for women and p < 0.0001 for men). Conversely, in LAlt, more women had grandparents (p < 0.0001) suffering from diabetes, and more women (p = 0.003) and men (p = 0.0002) had parents with diabetes as compared with HAlt residents.

Risk stratification of T2DM in residents of LAlts and HAlts (Table 3)

Risk stratification of T2DM showed that among women of Chu, 7.2% had moderate risk and 4.7% had high risk, whereas 9.5% of women of Naryn had moderate risk and 1.9% had high risk that rises with age (ρ = +1.000, p < 0.05). Overall, 3.8% and 1% of men in Chu had moderate and high risk of T2DM with moderate association with age (ρ = +0.350, p < 0.05). Among men of Naryn, 4.2% had moderate risk and 1% had high risk of T2DM increasing with age (ρ = +1.000, p < 0.05). There were no very high-risk groups in both altitudes.

Table 3.

Age- and Sex-Dependent Risk Stratification of Diabetes in Native Residents of High- and Low Altitudes

FINDRISK	<45 years	45–54 years	55–64 years	>64 years	Total
Women residents of high-altitude Naryn region
<7 points (low risk)	308 (40.3)	55 (7.2)	18 (2.4)	5 (0.6)	386 (50.5)^a
7–11 points (slightly increased risk)	61 (7.9)	116 (15.2)	72 (9.4)	43 (5.6)	292 (38.1)
12–14 points (moderate risk)	2 (0.3)	9 (1.2)	16 (2.1)	45 (5.9)	72 (9.5)
15–20 points (high risk)	1 (0.1)	3 (0.4)	4 (0.5)	7 (0.9)	15 (1.9)
>20 points (very high risk)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Women residents of low-altitude Chu region
<7 points (low risk)	463 (38)	78 (6.4)	12 (0.9)	4 (0.3)	557 (45.6)
7–11 points (slightly increased risk)	152 (12.5)	182 (14.9)	129 (10.6)	55 (4.5)	518 (42.5)
12–14 points (moderate risk)	9 (0.8)	21 (1.8)	26 (2.2)	29 (2.4)	85 (7.2)
15–20 points (high risk)	0 (0)	17 (1.4)	26 (2.2)	13 (1.1)	56 (4.7)^b
>20 points (very high risk)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Male residents of high-altitude Naryn region
<7 points (low risk)	329 (51)	83 (12.9)	48 (7.5)	15 (2.3)	475 (73.7)^c
7–11 points (slightly increased risk)	8 (1.3)	45 (6.5)	34 (5.3)	49 (7.6)	136 (21.1)
12–14 points (moderate risk)	1 (0.2)	5 (0.7)	6 (0.9)	12 (2.4)	28 (4.2)
15–20 points (high risk)	1 (0.2)	1 (0.2)	1 (0.2)	3 (0.4)	6 (1)
>20 points (very high risk)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Male (residents of low-altitude Chu region
<7 points (low risk)	276 (48.9)	62 (10.9)	29 (5.3)	22 (3.9)	389 (69)
7–11 points (slightly increased risk)	31 (5.5)	57 (10.1)	39 (6.9)	15 (2.6)	142 (25.1)
12–14 points (moderate risk)	4 (0.7)	7 (1.3)	5 (0.9)	5 (0.9)	21 (3.8)
15–20 points (high risk)	0 (0)	5 (0.9)	5 (0.9)	2 (0.3)	12 (2.1)^d
>20 points (very high risk)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)

p = 0.047, as compared with women of the same risk group of low-altitude Chu.

p = 0.0018, as compared with women of the same risk group of high-altitude Naryn.

p = 0.0743, as compared with men of the same risk group of low-altitude Chu.

p = 0.0990, as compared with men of the same risk group of high-altitude Naryn.

Comparison of risk profiles for T2DM of LAlt and HAlt populations demonstrated that more women in LAlt were at high risk (p = 0.0018) as compared with Halt; conversely, more than half of the surveyed women in Naryn carried a low risk of T2DM as compared with the women of Chu (p = 0.047). In men, there was a trend toward a higher prevalence of high risk at LAlt as compared with HAlt (p = 0.099) and a trend toward a higher prevalence of low risk of T2DM in residents of HAlt as compared with residents of LAlt (p = 0.0743).

Discussion

Our study of T2DM risk factors at different altitudes in the Kyrgyz population demonstrated a higher prevalence of overweight/obesity and abdominal obesity in residents of LAlt as compared with HAlt. The prevalence of overweight/obesity reduced with increases in altitude and age, irrespective of gender. PhA was low in older women (>64 years) residing at LAlt, whereas intake of antihypertensive drugs was higher among older women at HAlt. Consumption of fruits and vegetables was significantly lower in residents of HAlt as compared with those residing in LAlt areas, irrespective of gender or age. A family history of T2DM was less prevalent in residents at HAlt, but it was significantly higher in men and women residing at LAlt. Stratification of 10-year risk of T2DM using the FINDRISC score demonstrated a high prevalence of low risk among women residing in HAlt, and conversely a high prevalence of women at high risk of T2DM living in LAlt areas. For men, a similar trend was noticed. We did not record any very high-risk groups for T2DM in both regions.

The excess in the prevalence of overweight/obesity and abdominal obesity in our population may be attributed, in part, to low consumption of fruit and vegetables and low PhA. There might be also a contribution from genetic inheritance in those with a family history of T2DM, though we did not perform genetic testing (Karasaki and Kashiwazaki, 2005) and used only the FINDRISC questionnaire. The low risk of T2DM in HAlt may be explained by the low prevalence of overweight/obesity, sedentary lifestyle, and family history, as compared with LAlt.

Our results agree with recent studies (Petersen et al., 2006; Sniderman, 2007; Chiu, 2011; Indulekha et al., 2011; Kodama et al., 2013; Nightingale et al., 2013) that suggested that obesity and genetic background of the population increase the risk of T2DM in Asians. On the other hand, our results of low risk for T2DM and obesity in HAlt can be explained by the effects of hypoxia (West et al., 1983; de Mol et al., 2014; Esenamanova et al., 2014) and support previous studies (Diaz et al., 1978; Srivastava et al., 1975; Castillo et al., 2007) that demonstrated lower blood glucose levels, and a low prevalence of T2DM and obesity in residents of HAlt.

In their cross-sectional study of 285,196 adult members of the U.S. population, Woolcott et al. (2014) demonstrated an independent inverse association between T2DM prevalence and HAlt. The prevalence of T2DM was significantly (odds ratio [OR]—0.84, 95% confidence interval [CI] 0.74–0.96) lower in men of HAlt (1500–3500 m), but not in women. Xu et al. (2015), in a population-based study in Tibet, reported a lower prevalence of T2DM and obesity in residents of altitudes >3500 m as compared with those residing at <3500 m.

Our results are in agreement with those studies demonstrating a low prevalence of overweight/obesity and low risk of T2DM (FINDRISC score) in residents of HAlt. The only difference was that we observed a significantly lower risk of T2DM in women residing in HAlt, whereas for men it had only a borderline significance. In a study by Woolcott et al. (2014), an association of T2DM with altitude was found only for the male population. This can be explained by the fact that in our study, the women of HAlt had low BMI and WC, high PhA than those of LAlt, and the majority had no family history of T2DM. The trend for men may be explained, in part, by a lower sample of men included in our study as compared with the female group, and we should consider other factors. Aymara women residing at HAlt in Northern Chile, despite one quarter of them being obese, had a low prevalence of T2DM because of high PhA and low plasma insulin levels (Santos et al., 2001). Andean highlanders (Herrera-Enriquez and Navarres Guerra, 2017), women, and men differed by predictors of increased WC: In women, only triglycerides and BMI were associated with increased WC; whereas in men, triglycerides, fasting plasma glucose, high-density lipoprotein cholesterol, and systolic blood pressure were determinants of increased WC. Studies on genetic polymorphism in Andean, Tibetan, and Bolivian populations suggest that women at HAlt had a genetically defined better adaptation to hypoxia-induced physiological stress, though the studies on genetic polymorphism(s) responsible for impaired glucose metabolism are scarce (Karasaki and Kashiwazaki, 2005; Beall, 2007; Jacovas et al., 2016).

Woolcott et al. (2015) reported lower levels of fasting plasma glucose in population of altitudes >3000 m as compared with <3000 m, and glycemia in highlanders does not depend on BMI, rather lifestyle and genetics contribute to impairment of glycemic control.

From a lifestyle and genetics perspective, the latest studies reported disparate results for Peruvian and Tibetan populations (Bernabe-Ortiz et al., 2016; Okumiya et al., 2016). In the Peruvian population, Bernabe-Ortiz et al. (2016) demonstrated an increase in frequency of new T2DM cases by 58% during a 24-month follow-up (relative risk—1.58, 95% CI 1.01–2.48) in highlanders (3825 m) as compared with the population residing at sea level. The authors suggested different mechanisms such as sympathetic activation, genetic, and growth factors with pancreatic β cell dysfunction that are intrinsic to highlanders of the Peruvian Andes, and changes in lifestyle contribute to the increase in the incidence of T2DM in highlanders. Okumiya et al. (2016) demonstrated that lifestyle changes (urban dwelling) and moderate hypoxia accelerate development of glucose intolerance at altitudes >3500 m; whereas at LAlt, mild hypoxia might be protective against glucose intolerance. In their study of Tibetan highlanders, intermediate hyperglycemia and fasting diabetes were associated with urban dwelling and farming, aging, overweight, dyslipidemia, polycythemia, moderate hypoxemia, and altitude levels of 3500–4499 m (OR 2.07, 95% CI 1.44–2.98, for intermediate hyperglycemia) and >4500 m (OR 3.59, 95% CI 1.75–7.37, for intermediate hyperglycemia and OR 4.36, 95% CI 1.33–14.31, for fasting diabetes-defining hyperglycemia) as compared with <3500 m (Okumiya et al., 2016).

We should also acknowledge the differences in the altitudes in our study and previous studies that included populations living at altitudes >3500/>4500 m. In our study, we examined the population living at a range of 2000–4000 m in Naryn that has a range of high peaks (4000–4500 m) and plateau regions (2000–2500 m), accepted in our country as HAlt areas that are appropriate for residence. The residents of HAlt villages are traditionally involved in stock-breeding, and there is also a mining industry and military presence at altitudes of 3200–4000 m (Esenamanova et al., 2014). A selected population of villages mostly consumes meat, dough and milk products, and less fruits and vegetables due to lack of farming at HAlt. Despite this, residents of HAlt in the Kyrgyz Republic have a low prevalence of obesity, T2DM, cardiovascular risk factors, and smoking as compared with LAlt (Esenamanova et al., 2014; Vinnikov et al., 2015). In addition, populations in rural areas usually have more active lifestyles as compared with urban residents. Thus, preventive measures of lifestyle changes should be applied in populations, irrespective of altitude of residence.

Study limitations

Our study has several limitations as a cross-sectional population-based design and risk stratification based on a questionnaire. We estimated only a 10-year risk of T2DM without measurement of fasting glucose levels, and studied only cardiovascular risk factors, without inclusion of broader socioeconomic factors. It should be noted that PhA level and consumption of fruits and vegetables were based on self-reported survey questions. Further prospective studies on the risk of T2DM in populations of HAlt and LAlt of the Kyrgyz Republic should be addressed. We should emphasize the strength of the study being a first comparing the risk of T2DM by using the FINDRISC score in native Kyrgyz populations at LAlt and HAlt.

Conclusions

In the Kyrgyz population, a 10-year high risk of T2DM development is greater among residents of LAlt as compared with HAlt, irrespective of gender. No very high-risk group was detected in residents of LAlt or HAlt. The leading composites of the FINDRISC score that predict T2DM are increased WC, BMI, and low intake of vegetables and fruits, but the risk is also dependent on the altitude of residence and age.

Footnotes

Acknowledgments

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

Author Disclosure Statement

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.

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