Clinical Profile and Risk Factors for Complication of Type 2 Diabetes Mellitus at the National Referral Hospital, Bhutan: A Descriptive Cross‐Sectional Study

ABSTRACT

Background and Aim

Globally, diabetes mellitus is a major public health concern affecting 10.5% of the population. Nearly 90% of these people have Type 2 diabetes mellitus (T2DM). In Bhutan, T2DM is prevalent in 5.6% of the population, and around 60% are unaware of their diagnosis of diabetes. There is no baseline information on the rate and the risk factors for complications of diabetes in Bhutan. The study assessed the clinical profile and the risk factors for complications of T2DM at the Jigme Dorji Wangchuk (JDW) National Referral Hospital, Bhutan.

Methods

A descriptive cross‐sectional study was conducted at the JDW National Referral Hospital, Bhutan, from January to December 2019. Patients with T2DM attending diabetic clinics were included in the study. Demographic variables and metabolic profiles were recorded using a standard pro forma. Descriptive statistics were used to express the results. The association of clinical profiles with the microvascular complication was assessed using multivariate logistic analysis with statistical significance at p < 0.05.

Results

There were 292 patients with T2DM during the study period. The rate of microvascular complication is around 25% in T2DM. Among the complications, diabetic retinopathy occurred in over 51%, followed by neuropathy (29.7%) and nephropathy (18.9%). Over 1/3rd of patients had a duration of diabetes over 10 years with a mean duration of 6.3 (5.4) years, and around 44% (127/292) of them had poor glycemic control (HbA1C ≥ 7%). The age ≥ 60 years and the duration of diabetes ≥ 10 years were independent risk factors for microvascular complications in T2DM patients. Regular exercise prevents retinopathy (OR 0.4, 95%CI 0.2–0.9, p = 0.026).

Conclusion

There is a microvascular complication in 1 in 4 of type 2 diabetic patients. Age over 60 years and a duration of diabetes of more than 10 years are independent risk factors for microvascular complications, and regular exercise is preventive for microvascular complications.

Abbreviations

BMI

body mass index

CI

confidence interval

FBS

fasting blood sugar

HDL

high density lipoprotein

HbA1C

glycosylated hemoglobin

JDW

Jigme Dorji Wangchuk

LDL

low density lipoprotein

PPBS

post prandial blood sugar

OR

odds ratio

REBH

Research Ethical Board of Health

STATA

statistical software for data science

T2DM

type 2 diabetes mellitus

WHO

World Health Organization

1. Introduction

Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use insulin and is induced by a genetic predisposition coupled with environmental factors [1]. The global prevalence of diabetes for the 20–79 age group is 10.5% and it is projected to rise to 12.2% by 2045 [2].

Diabetes is classified as Type 1 diabetes, Type 2 diabetes (T2DM), hybrid forms of diabetes, other specific types, unclassified diabetes, and hyperglycemia first detected during pregnancy [3], among which T2DM is the most common type accounting for over 90% of the patients with diabetes [4].

The risk factors for T2DM include genetic susceptibility, obesity, unhealthy dietary habits, smoking and alcohol consumption, sedentary lifestyle, and less physical activity [5, 6].

Diabetes affects many organ systems and is a major cause of morbidity and mortality associated with the disease. Diabetes‐related complications are divided into vascular and nonvascular complications. The vascular complications of T2DM can present as macrovascular (coronary heart disease, peripheral artery disease, cerebrovascular disease) and microvascular (retinopathy, neuropathy, and nephropathy) complications [7, 8].

Microvascular complications mainly develop due to uncontrolled hyperglycemia, and the synergistic effects of smoking, hypertension, dyslipidemia, and genetic and hereditary susceptibility also contribute [9].

The global prevalence of microvascular complications in people with T2DM ranges from 14.5% to 23.5% [10]. Of which the prevalence of diabetic retinopathy, nephropathy, and neuropathy are 35%, 30%–50%, and 16%–87% respectively [11, 12, 13].

Intensive glycemic control can modestly reduce the onset or slow the progression of microvascular complications in T2DM by 1% to 10% [14]. Lifestyle changes including cessation of smoking and alcohol intake, staying physically active, managing dyslipidemia, and controlling blood pressure along with renal function monitoring are the other ways to prevent diabetic microvascular complications [15].

In Bhutan, based on a National Health Survey (2023), the prevalence of diabetes is 5.6%, and almost 60% of those with diabetes are unaware of their diagnosis. Among those aware of the diagnosis, nearly 1.3% of diabetic patients are not on treatment, 13.5% are on treatment with uncontrolled diabetes, and only 25.8% on treatment are with controlled blood sugar [16]. Anecdotal evidence shows a significant number of diabetic patients are either not on treatment or their blood sugar is poorly controlled, and expecting more complications of T2DM in Bhutan. This study aimed to evaluate the rate of complications of T2DM and risk factors associated with complications of T2DM.

2. Methods

2.1. Study Design

This was a descriptive cross‐sectional study.

2.2. Study Site

The study was carried out at the diabetes clinic at the Jigme Dorji Wangchuck (JDW) National Referral Hospital, Thimphu Bhutan.

2.3. Study Period

The study was conducted over 1 year from January 1, 2019 to December 30, 2019.

2.4. Study Population

All the patients diagnosed with T2DM visited diabetic clinics at JDW National Referral Hospital during the study period.

2.5. Study Setting

Bhutan is a small land‐locked country in the Himalayas sandwiched between China and India with a total population of over 0.7million [17]. Healthcare in Bhutan is publicly owned and solely state‐funded. It has a three‐tiered health system with the Primary Health Center at the lowest level followed by district hospitals, regional referral hospitals, and the national referral hospital [17].

There are diabetic clinics at the regional and national referral hospitals. At the JDW National Referral Hospital, the diabetic clinic is conducted twice a week and it is run by a physician and a clinical nurse. The diabetes clinic has about 3500 patients registered for care of which over 90% are T2DM. On average, 90 patients visit the clinic on scheduled days. The nurse measures the pulse, blood pressure, and BMI as an initial screening process before being seen by the physician. For uncomplicated and euglycemic patients, blood investigations such as fasting and 2‐h postprandial blood sugar were monitored monthly and Hb1Ac, renal and liver functions, lipid profile, and 24‐h urinary protein level were reviewed every 3 months. A neurological and fundoscopic examination is advised every 6 months. Those with diabetic‐related complications and poor glycemic control were followed up more frequently. Diabetic patients are treated with oral diabetic agents or insulin depending on the blood sugar levels.

2.5.1. Inclusion Criteria

Patients diagnosed with T2DM were included in the study. Diagnosis of T2DM is made based on the American Diabetes Association guideline with the presence of one criterion of the following, fasting glucose ≥ 126 mg/dL (≥ 7 mmol/L) or 2 h plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L) after 75 g glucose load or random plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L) in a patient with typical symptoms of diabetes, or glycosylated hemoglobin (HbA1C) ≥ 6.5% (48 mmol/mol) [18].

2.5.2. Exclusion Criteria

Patients diagnosed with other categories of diabetes including type 1 diabetes, hybrid forms of diabetes, other specific types, unclassified diabetes, and hyperglycemia first detected during pregnancy (gestational diabetes mellitus and diabetes in pregnancy) were excluded from the study.

2.5.3. Sample Size Calculation

The sample size was determined using Cochran's formula for a single population proportion considering the following assumptions: 95% confidence interval (Z = 1.96), and 5% margin of error (e = 0.05). The prevalence (p) of T2DM is 23% (p = 0.23); and q = 1‐p; n = sample size.

$$n=\frac{z^{2}pq}{e^2}$$

$$=[{\left(1.96\right)}^2\times 0.23\times \left(1-0.23\right)]/{\left(0.05\right)}^2=282$$

Considering a 10% dropout rate, the final sample size was 310.

2.6. Sampling Method

A systematic random sampling method was used to select the patients. On average 90 patients visit each clinic day. Five patients were invited to participate in the study every clinic day. Every 18th patient was enrolled (90/5 = 18). This required 62 clinic days to complete data collection which accounted for government and public holidays on some of the diabetes clinic days.

2.7. Data Collection Procedures

An administrative clearance was obtained from the Ministry of Health, and an ethical clearance was obtained from the Research Ethical Board of Health, Bhutan (Reference No: REBH/Approval/2018/055, dated December 31, 2018). The patients with T2DM at the diabetic clinic were invited to participate in the study, and those who consented to participate were included in the study. After obtaining informed written consent, the investigators conducted the history and examination including fundoscopy and neurological examination, and reviewed the investigation reports. The demographic variables (age, gender, body mass index, blood pressure, duration of diabetes, level of education, smoking status, alcohol intake, and physical activities) and the metabolic profiles (low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), triglyceride, total cholesterol, and glycosylated hemoglobin (HbA1C) levels) were recorded using a standard proforma. Complications of T2DM retinopathy, nephropathy, and neuropathy were assessed and recorded.

Duplication of data due to frequent visits to the clinic was checked using the patient's name, and citizenship identity card number and removed from the final data set.

2.8. Operational Definition

2.8.1. Diabetic Neuropathy

The diagnosis of diabetic neuropathy is done based on the standard assessment for signs and symptoms using a Michigan Neuropathy Screening Instrument [19].

2.8.2. Diabetic Nephropathy

Nephropathy was diagnosed based on 24‐h urinary protein > 300 mg/day, and or eGFR < 60 mL/min/1.73 m² [20].

2.8.3. Physical Activity

Based on the American Diabetic Association, a minimum of 150 min of moderate to vigorous exercises per week is recommended and considered adequate for people with diabetes [21].

2.8.4. Body Mass Index (BMI)

BMI is an index calculated using the height and weight of a person to provide an estimate of body fat in males and females of any age. BMI calculation is shown:

$$\text{BMI}=\frac{\text{weight}(\text{kg})}{\text{Height}{(\mathrm{m})}^2}$$

BMI is classified as underweight (BMI < 18.5), normal weight (BMI 18.5–24.9), overweight (BMI 25–29.9) and obese (BMI ≥ 30) based on WHO classification [22].

2.9. Data Management

Data collectors and the nurses of diabetic clinics were trained on the study instrument, consent form, data collection procedure, and confidentiality of the respondents. The collected data were checked for completeness daily by the investigators to monitor the overall quality of the data collection process.

2.10. Data Analysis

Data was double entered in EpiData Entry (version 3.1, EpiData Association, Odense, Denmark) and analyzed in EpiData analysis version 2.2.2.183 and STATA version 13.1. Descriptive data were presented as frequency, percentage, mean, or standard deviation. Multivariate logistic regression analysis was performed to find the association of clinical profiles with microvascular complications, and the statistical significance level was considered at p < 0.05 level.

2.11. Human Ethics and Consent to Participate Declarations

The study was performed in accordance with the Declaration of Helsinki. Ethical clearance was obtained from the Research Ethics Board of Health, Ministry of Health, Bhutan with reference number: REBH/Approval/2018/055, dated December 31, 2018 (Link to Ethical Review Board: https://www.moh.gov.bt/about/program-profiles/357-2/). Written informed consent was obtained from all the study participants.

3. Results

3.1. Sociodemographic Profile

There were 292 patients with T2DM during the study period. More than 90% of the patients (266/292) were age 40 years and older; the majority of them were female (61.6%, 180/292), overweight and or obese (75%, 219/292), and illiterate (62,7%, 183/292). Over 1/3rd of patients had a duration of diabetes over 10 years with a mean duration of 6.3 (5.4) years (Table 1).

Table 1.

Sociodemographic profile of patients with T2DM at the JDW National Referral Hospital, Thimphu, Bhutan, 2019.

Sociodemographic characteristics	n (%)
Age (years)
< 40	26 (8.9)
40–59	138 (47.2)
≥ 60	128 (43.9)
Gender
Male	112 (38.4)
Female	180 (61.6)
Body Mass Index (kg/m2)
< 18.5	1 (0.3)
18.5–24.9	72 (24.7)
≥ 25	219 (75.0)
Duration of diabetes (years)
< 10	212 (72.7)
10–19	70 (23.9)
> 20	10 (3.4)
Mean duration of diabetes, mean (SD)	6.3 (5.4)
Level of education
Illiterate	183 (62.7)
Primary/nonformal education	52 (17.8)
High school	25 (8.5)
Certificate/Diploma/Graduate	20 (6.9)
Monastic education	12 (4.1)
Smoking status
Yes	7 (2.4)
No	285 (97.6)
Alcohol intake
Yes	14 (4.8)
No	278 (95.2)
Physical exercise
≥ 150 min/week	150 (51.4)
< 150 min/week	142 (48.6)

3.2. Metabolic Profile

Over 2/3rd T2DM patients were hypertensive (35%, 103/292), more than 43% had poor glycemic control as evidenced by elevated levels of HbA1C (43.5%, 127/292), and around 22% had a high level of total cholesterol levels (n = 63). The details of the metabolic profiles of the study subjects are shown in Table 2 below.

Table 2.

Metabolic profile of patients with T2DM at the JDW National Referral Hospital, Thimphu, Bhutan, 2019.

Metabolic parameters	Total	Male	Female
	n (%)	n (%)	n (%)
Hypertension
Normal	189 (64.7)	76 (67.9)	113 (62.8)
Hypertension	103 (35.3)	36 (32.1)	67 (37.2)
HbA1C
Good control (≤ 7%)	165 (56.5)	65 (58.1)	100 (55.6)
Poor control (> 7%)	127 (43.5)	47 (41.9)	80 (44.4)
HDL cholesterol
≥ 40 mg/dL	248 (84.9)	90 (80.4)	158 (87.8)
< 40 mg/dL	44 (15.1)	22 (19.6)	22 (12.2)
LDL Cholesterol
≥ 100 mg/dL	115 (39.4)	38 (33.9)	77 (42.8)
< 100 mg/dL	177 (60.6)	74 (66.1)	103 (57.2)
Total cholesterol
< 200 mg/dL	229 (78.4)	89 (79.5)	140 (77.8)
≥ 200 mg/dL	63 (21.6)	23 (20.5)	40 (22.2)
Triglyceride
> 150 mg/dL	68 (3.4)	28 (25.0)	40 (22.2)
≤ 150 mg/dL	224 (96.6)	84 (75.0)	140 (77.8)

Abbreviations: HbA1C, glycosylated hemoglobin; HDL, high density lipoprotein; LDL, low density lipoprotein.

3.3. Microvascular Complications

Of 292 patients with T2DM, over 25% (n = 74) had microvascular complications. Among the microvascular complications, more than half are retinopathy (51.4%, 38/74), and around 95% of the retinopathy is non‐proliferative (Table 3).

Table 3.

Types of microvascular complications in patients with T2DM at the JDW National Referral Hospital, Thimphu, Bhutan, 2019.

Microvascular complications (n = 74)	n (%)
Retinopathy	38 (51.4)
Neuropathy	22 (29.7)
Nephropathy	14 (18.9)
Retinopathy (n  = 38)
Nonproliferative	36 (94.7)
Proliferative	2 (5.3)
Number of complications (n  = 74)
Any one complication	45 (60.8)
Any two complications	21 (28.4)
All three complications	8 (10.8)

3.4. The Association of Risk Factors for Complications of Type 2 Diabetes

The microvascular complications were significantly associated with age ≥ 60 years (OR 3.27, 95% CI 1.8 ‐ 6.0, p < 0.001) and duration of diabetes ≥ 10 years (OR 11.9, 95% CI 6.2‐22.9, p < 0.001). Regular exercise was shown to have a preventive effect against the development of diabetic retinopathy (OR 0.4, 95% CI 0.2‐0.9, p < 0.026). The details of the association of risk factors for complications of diabetes are shown in Table 4.

Table 4.

Risk factors associated with microvascular complications in T2DM at the National Referral Hospital, Thimphu, Bhutan, 2019.

Risk factors		Retinopathy	p‐value	Nephropathy	p‐value	Neuropathy	p‐value	Any one complication	p‐value
		OR (95% CI)		OR (95% CI)		OR (95% CI)		OR (95% CI)
Age group
	< 60 years	Reference		Reference		Reference		Reference
	≥ 60 years	2.5 (1.2–5.0)	0.012	3.1 (1.5–6.4)	0.003	2.9 (1.8–7.5)	0.021	3.3 (1.8–6.0)	< 0.001
Gender
	Male	Reference	Reference	Reference		Reference		Reference
	Female	0.9 (0.5–1.9)	0.879	0.7 (0.4–1.4)	0.311	0.7 (0.1–0.2)	0.478	0.8 (0.4–1.4)	0.374
Duration of Diabetes
	< 10 years	Reference		Reference		Reference		Reference
	≥ 10 years	18.5 (4.6–7.7)	< 0.001	4.3 (1.8–10.7)	0.001	14.5 (6.3–33.6)	< 0.001	11.9 (6.2–22.9)	< 0.001
BMI (kg/m2)
	< 18.5	Reference		Reference		Reference		Reference
	18.5‐24.9	3.5 (0.9–13.8)	0.08	0.1 (0.4–3.4)	0.85	0.6 (0.2–2.6)	0.534	1.2 (0.4–3.3)	0.745
	≥ 25	1.3 (0.4–4.5)	0.693	0.4 (0.2–1.0)	0.054	0.4 (0.1–1.1)	0.065	0.6 (0.3–1.3)	0.201
HbA1C
	Good control (< 7%)	Reference		Reference		Reference		Reference
	Poor control (≥ 7%)	0.6 (0.3–1.3)	0.219	1.4 (0.7–2.9)	0.304	1.6 (0.7–3.9)	0.280	0.9 (0.6–1.8)	0.978
Total cholesterol
	< 200 mg/dL	Reference		Reference		Reference		Reference
	≥ 200 mg/dL	0.3 (0.1–0.9)	0.068	0.2 (0.0–0.8)	0.022	0.2 (0.0–1.2)	0.076	0.2 (0.7–0.6)	0.004
Triglyceride
	≤ 150 mg/dL	Reference		Reference		Reference		Reference
	> 150 mg/dL	0.9 (0.4–1.7)	0.681	0.8 (0.4–1.6)	0.542	0.7 (0.3–1.7)	0.389	0.6 (0.3–1.3)	0.200
Smoking
	No	Reference		Reference		Reference		Reference
	Yes	1.1 (0.1–9.5)	0.919	1.2 (0.1–9.9)	0.897	—	—	0.6 (0.1–5.4)	0.681
Exercise for more than 150 min/week
	No	Reference		Reference		Reference		Reference
	Yes	0.4 (0.2–0.9)	0.026	0.7 (0.3–1.4)	0.292	0.9 (0.4–2.3)	0.894	0.8 (0.4–1.3)	0.269
Alcohol
	No	Reference		Reference		Reference		Reference
	Yes	0.5 (0.1–3.9)	0.512	0.5 (0.1–4.1)	0.531	0.9 (0.1–7.6)	0.955	0.3 (0.0–2.2)	0.232
Hypertension
	Normal	Reference		Reference		Reference		Reference	—
	Hypertension	1.1 (0.5–2.2)	0.828	1.1 (0.6–2.3)	0.727	1.3 (0.5–3.1)	0.566	1.2 (0.7–2.1)	0.578

Abbreviations: BMI, Body mass index; HbA1C, glycosylated hemoglobin; OR, odds ratio.

4. Discussion

In the current study, the rate of microvascular complications in T2DM was around 25%. A comprehensive review of literature conducted in the US on microvascular complications showed the same prevalence rate of 25% [23] and a similar rate (26%) was reported from Ethiopia [24].

In the present study, at least one complication was present (either retinopathy, nephropathy, or neuropathy) in 60%, which is quite high. At least one complication present was significantly less in the prevalence study in China as compared to the present study finding (34% vs 60%) [25]. The differences in the rate of complications between the countries could be due to the difference in treatment regimens, compliance with the treatment, and the quality of medicines used for the treatment.

The prevalence of hypertension in type 2 diabetes in Bhutan is 35%. The cross‐sectional study conducted in other countries like Ethiopia (55%), Afghanistan (70%), and Tanzania (55%) is comparatively high as compared to hypertensive prevalence in the current study [26, 27, 28]. Bhutan is a mountainous country and the majority of the people walk to the office and back home unlike the people in other countries who drive cars wherever they go. Physical inactivity, a sedentary lifestyle, and an unhygienic diet must be factors for the higher prevalence rate of hypertension in other countries.

Factors associated with complications of diabetes are older age, early onset of diabetes, duration of diabetes, presence of hypertension, dyslipidemia, and poor glycemic controls [23, 25, 26]. The current study showed only longer duration of diabetes (≥ 10 years) and the older age of the patients (> 60 years) are independently associated with microvascular complications of T2DM. Other factors like the presence of hypertension, dyslipidemia, and poor glycemic control are not found to be associated with complications of diabetes in the current study. This is because, in the current study, there were only a few cases of hypertension, dyslipidemia, and patients with poor control of diabetes.

Regular exercise improves blood glucose control by sensitizing the insulin receptors, reduces cardiovascular risk factors associated with diabetes, improves dyslipidemia, and regulates BMI. Exercise prevents most of the complications of type 2 diabetes including microvascular and macrovascular complications [29]. Daily performing regular exercise (a minimum of 150 min of moderate to vigorous exercises per week) is found to have a preventive effect on retinopathy by almost 60% in the present study.

One interesting finding from this study is the higher proportion of overweight and obese diabetic population which stood at 75%. Although not analyzed in our study, obesity was related to poor glycemic control and dyslipidemia in the diabetic population [30, 31]. In the current study, around 44% of our participants had poor glycemic control with elevated glycosylated hemoglobin.

5. Limitation

Since this was a single center‐based study, we were not able to assess the exact prevalence of the disease complications. As such, the actual burden of the disease could not be generalized for the whole country. Due to the scarcity of laboratory resources and a higher percentage of illiterate participants, the diagnosis of nephropathy might have been less accurate in our setting.

6. Conclusion

One in four patients with type 2 diabetes is having complications of diabetes. The relatively older patients with a longer duration of diabetes resulted in diabetic microvascular complications, and regular exercise is preventive for complications of diabetes. With the demographic transition of the aging diabetic population and the duration of diabetes, preventive measures to decrease microvascular complications need to be strengthened. Good glycemic control and regular screening of diabetic complications are recommended at the practice level. Lifestyle modification to avert adverse metabolic profile is recommended at the policy level.

Author Contributions

Tshering Norbu: conceptualization; methodology; investigation; validation; formal analysis; supervision; writing–review & editing; writing–original draft. Yeshey Dorjey: conceptualization; methodology; data curation; investigation; validation; visualization; formal analysis; supervision; writing–review & editing; writing–original draft. Sangay Tshering: conceptualization; methodology; writing–review & editing; Validation; Data curation; Writing–original draft. Namkha Dorji: conceptualization; methodology; data curation; validation; investigation; writing–review & editing. Guru Prasad Dhakal: conceptualization; methodology; data curation; validation; Investigation; writing–review & editing.

Disclosure

The lead author Yeshey Dorjey affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Ethics Statement

This research was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. The study was approved by the Research Ethics Board of Health, Ministry of Health, Bhutan with Reference number: REBH/Approval/2017/072, dated 4/12/2017.

Consent

Informed written consent for publication was obtained from all the study participants who were included in the study.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.