Vascular Complications and their Risk Factors in Patients of Diabetes Mellitus, Type 2

Tariq Farhad1 ,Muhammad Rahim Burghri2 ,Muhammad Uzair Memon3,Soha Fatima4,Yasir Latif5,Abdullah Memon66

1General Practitioner, Department of Family Medicine, Ambulatory Health Services, SEHA, Abu Dhabi.

2Assistant Professor, Department of Anatomy, Muhammad Medical College, Mirpurkhas.

3Medical Officer, Department of Medicine, Isra University, Hyderabad.

4House officer, Medicine, Jinnah Postgraduate medical Centre, Karachi.

5Medical Officer, Indus Hospital, Badin Indus Hospital, Badin.

6Medical Student, Third year MBBS Isra University, Hyderabad.

Introduction:To evaluate the vascular complications and their correlation with different risk factors among type-2 diabetic patients in Hyderabad, Sindh, Pakistan.
Methodology:This cross-sectional study was conducted at the department of medicine Isra University Hospital, Hyderabad from March to September 2021. Type 2 diabetics of either sex, between ages 20 and 70 years, on diabetic medication, were included in the study. While patients with type I diabetes, unconscious or with any mental health issues were excluded. A Non-random consecutive sampling technique was applied for the selection of participants. Socio-demographic, disease and medication information was collected using a written questionnaire while serum glucose level, albumin and lipid profile were analyzed.
Results:Over half of the participants (51.72%) were females, while most (70.87%) of the participants were aged < 40 years. A total of 124(28.5%) patients showed symptoms of macro-vascular complications with most (16.78%) of them having coronary artery disease. A significant relation (p<0.05) was found between coronary artery disease and age, duration of diabetes, blood pressure, body mass index and serum triglycerides. Peripheral vascular disease was significantly related (p<0.05) to the duration of diabetes, systolic blood pressure and serum triglyceride. Further significant relation (p<0.05) between cerebrovascular disease with age, systolic and diastolic BP was there.
Conclusion: Coronary artery disease seems to be the most common macro-vascular complication among type 2 diabetic patients, with a high prevalence of risk factors such as advanced age, duration of DM, male sex, hypertension, Body Mass Index, and serum triglycerides.
Key words:Coronary artery disease, diabetes mellitus type 2, Macro-vascular complications, peripheral vascular disease.

Diabetes mellitus (DM), is a universally occurring non-communicable disease affecting people worldwide1.The overall incidence of DM is increasing at a staggering rate and this rise in number poses an enormous social and economic burden to the population. International diabetes federation reported that roughly 463 million people between ages 20 and 79 years are living with DM, this toll is expected to rise up to 700 million by 2045. Over two third of DM cases are residing in low and middle-income countries.2
Diabetes mellitus Type 2 (DMT2) is the most common type of DM that accounts for around 90% of DM cases throughout the globe.3Approximately, 374 million people are already at risk of developing type 2 diabetes worldwide.1Numerous micro and macro-vascular complications are associated with DMT2 that may have severe individual and social consequences.4Peripheral neuropathy (PN) and peripheral vascular disease (PVD) are long-term complications of diabetes and are difficult to diagnose because they are asymptomatic, resulting in foot ulceration, infection, and ultimately amputation. Early detection and treatment, on the other hand, reduce the incidence of ulceration.5Other macro-vascular complications like Coronary artery diseases (CAD) and cerebrovascular diseases like stroke are rapidly growing and strongly associated with DMT2 and 2-4 folds more common in DMT2 patients compared with those without diabetes.6According to the world health organization (WHO), the prevalence of CAD only in the Eastern Mediterranean region (EMRO) is 54% while these deaths may vary from 13% to 49% depending on the country. It also accounts for a considerable number of deaths in the region.7
Pakistan is a low-middle income country where overall 70% of the global burden of diabetics is present.8The IDF reported the prevalence of DM is 6.8% during the year 2019 among 20–79 years’ age adults in Pakistan. While the prevalence of DMT2 has risen significantly, 33 million adults in Pakistan are affected by this type of diabetes which is a 70% increase in toll since 2019. With the rise in the prevalence of DMT2 in Pakistan, the complications associated with the disease are also on the rise. Studies have reported that among the complications, CAD is a more frequently reported complication of DMT2.9 While a significant relationship betweenDMT2 and stroke in Asian countries like Pakistan also reported by different studies. Despite this rise in prevalence, very limited studies have reported the burden of DM complications and the risk factors linked with the complications of the disease in the country.10
Prevalence studies on the complications of DM give noticeable and significant information that have a significant impact on policy and practice. But still the scantiness of information related to the risk factors for the co-morbidities in DM patients in Pakistan specially in Sindh and its cities demand a need for attention, screening and interventional program to estimate the prevalence and correlation of risk factors of different co-morbidities of DM in Sindh. For this reason, the present study was designed with an objective to evaluate the macro-vascular complications and its relationship with different risk factors among type-2 diabetic patients in at tertiary care hospital of Hyderabad, Sindh, Pakistan.

After getting ethical approval from ethical and research review committee of Isra University # IU/RR-10-IRC-21/N/2021/037, cross-sectional study was conducted at the department of medicine Isra University Hospital (IUH), Hyderabad from March to September 2021. All patients admitted or visited the medicine department Hyderabad with positive history of DMT2, taking any diabetic medication (insulin or oral hypoglycemic drugs or both), between age of 20 and 70, either sex, regardless of socioeconomic status or religion, given consent of participation were included in the study. Patients with type I DM, not willing to participate, mentally compromised or unconscious were excluded from the study.
Informed consent was obtained from all the participants individually prior to the commencement of the interviews. Sample size was calculated using online sampling calculator Open-epi.11 Keeping 95% confidence interval, 5% margin of error and prevalence of macro-vascular complications among type II diabetics of 27.2% 15, after adding ±10% a sample size of 335 was Calculated. Non-random consecutive sampling technique was applied for the selection of participants. A pre-designed and pre-tested written questionnaire was used to collect information of all the study participants.
The questionnaire comprised of three parts, first part of the questionnaire having questions regarding socio-demographic variables like; age, sex, economic status, education status. Second part of the questionnaire with information of Body Mass Index (BMI), duration of disease, medication history, family history of diabetes and smoking history. The third section contains the details of the laboratory diagnostic as well as any comorbidities discovered during the test.
The height was measured without shoes and the body weight was estimated while wearing the least amount of clothing possible using stadiometer with weighing scale. The usual formula (weight (kg) per height) was used to calculate BMI (m2) that is if a person having BMI between 18.5 and 24.9 was labelled as healthy while BMI <18.5 (Underweight), 25.0-29.9 (overweight) and ≥30.0 was considered as obese.
Using aseptic measures, 5cc of blood was drawn and sent for serum glucose (Random and Fasting) levels, Glycated hemoglobin (HbA1c), and total lipid profile were measured on a fully automated chemistry analyzer.Blood pressure was measured using a mercury sphygmomanometer by trained nursing staff to assess the patient’s hypertension (HTN) status using the WHO standard definition for HTN. Peripheral neuropathy was assessed by testing the strength of muscles, Monofilament as well as tendon reflex. Patients with painful PN were confirmed if they had a history of body pain that worsened at night. Diabetic nephropathy was evaluated by urinalysis for macro and micro-albuminuria.
SPSS version 22 was used for statistical analysis. Descriptive statistics were used to show demographic variables and co-morbidities. For quantitative data, mean and standard deviation (SD) were calculated. The relationship between macro-vascular disease and clinical variables was determined using the Student t-test. P < 0.05 was considered significant.

A Total of 335 patients fulfilled the selection criteria; Of them 173 (51.6%) were females and 162 (48.4%) were males. Most (70.8 %) participants belong to 40 and above year while 29.13% were younger than 40 years of age. The mean age of participants was 48.7 ± 10.9 years (age range 27-71 years). The duration of DM was between 3–31 years with the mean duration of DM being 8.7±4.6 years. HbA1c levels revealed that 86.58% of all participants had levels ≥ 7%.

Table I: Complications prevalent among diabetic patients (n=335)

Complications

n (%)

Coronary artery disease

56 (16.7)

Diabetic Nephropathy

53 (16.0)

Diabetic Neuropathy

104(31.0)

Diabetic Retinopathy

82 (24.5)

Cerebrovascular disease

22 (6.5)

Peripheral vascular disease

18 (5.3)


Table II: Socio-demographic and clinical details of study participants (n=335)

n

%

Family history of DM

159

47.5%

Duration of DM

Upto 5 years

Over 5 years

108

227

32.3

67.7

Hypertension (mmHg) (n=254)

Systolic HTN

Diastolic HTN

157

97

62.0

38.0

BMI (kg/m2)

Normal

Overweight

Obese

191

114

30

57.0

34.0

9.0

Smoker

Yes

128

38.2

Laboratory findings

Mean

S.D

Glycemic status (mean)

FBS (mg/dL)

2 hours ppbg* (mg/dL)

HbA1c (%)

210.1

309.4

9.6

87.5

112.9

2.5

Lipid profile (mg/dL) (mean)

Total cholesterol

HDL Cholesterol

LDL Cholesterol

TGs

188.2

42.1

141.2

221.5

48.1

28.7

43.7

115.4


Table III: Gender wise distribution of demographic, clinical and laboratory findings (n=335)

SOCIO-DEMOGRAPHIC & CLINICAL FEATURES

Male

Female

173

162

n

%

n

%

Family history of DM

91

52.6

68

42.3

Duration of DM

Upto 5 years

Over 5 years

45

128

26.0

74.0

63

99

39.0

61.0

BMI (kg/m2)

Normal

Overweight

Obese

114

44

15

66.0

25.4

8.6

77

70

15

47.6

43.2

9.2

Smoker

110

63.6

18

11

LABORATORY FINDINGS

Mean

S.D

Mean

S.D

Glycemic status

FBS (mg/dL)

2 hours ppbg* (mg/dL)

HbA1c (%)

203.5

301.7

8.81

81.3

100.3

2.4

206.4

309.6

9.4

92.1

115.2

2.7

Lipid profile (mg/dL)

Total cholesterol

HDL Cholesterol

LDL Cholesterol

TGs

186.2

43.5

140.3

231.1

47.7

26.7

42.6

126.9

188.8

42.6

143.5

213.1

47.9

25.4

45.3

103.4


Table IV: Macro-vascular complications and their relation with different risk factors

PERIPHERAL VASCULAR DISEASE

Yes

18

No

317

P-value

Mean

±S.D

Mean

±S.D

Age (years)

54.6

8.4

53.9

9.6

0.73

Duration of DM (years)

11.4

8.4

5.9

6.2

0.00*

Systolic BP (mmHg)

144.5

22.7

134.4

21.1

0.02*

Diastolic BP (mmHg)

88.5

13.7

84.9

11.5

0.14

HbA1C (%)

8.6

2.1

9.3

2.7

0.22

BMI (kg/m2)

22.7

3.4

23.8

3.9

0.18

Serum Cholesterol (mg/dL)

182.6

56.3

188.4

43.3

0.53

HDL Cholesterol (mg/dL)

41.5

27.8

43.3

26.5

0.75

Serum Triglyceride (mg/dL)

285.5

113.7

237.3

112.6

0.04*

LDL Cholesterol (mg/dL)

136.1

47.3

144.5

42.7

0.36

CORONARY ARTERY DISEASE

Yes

56

No

279

P-value

Mean

±S.D

Mean

±S.D

Age (years)

58.4

10.4

51.7

10.7

0.00*

Duration of DM (years)

10.7

6.8

5.8

6.2

0.00*

Systolic BP (mmHg)

148.3

27.8

135.3

26.5

0.00*

Diastolic BP (mmHg)

89.3

15.8

83.5

13.8

0.00*

HbA1C (%)

9.4

2.3

9.2

2.1

0.46

BMI (kg/m2)

24.4

3.6

22.3

4.1

<0.001*

Serum Cholesterol (mg/dL)

185.4

51.3

189.3

47.4

0.52

HDL Cholesterol (mg/dL)

45.7

42.4

40.1

19.3

0.07

Serum Triglyceride (mg/dL)

240.2

151.5

211.3

100.8

0.04*

LDL Cholesterol (mg/dL)

140.9

44.8

141.2

43.6

0.95

CEREBROVASCULAR DISEASE

Yes

22

No

313

P-value

Mean

±S.D

Mean

±S.D

Age (years)

59.6

11.2

50.6

11.3

<0.001*

Duration of DM (years)

9.4

5.2

7.4

5.4

0.058

Systolic BP (mmHg)

150.3

26.8

135.7

25.4

0.003*

Diastolic BP (mmHg)

90.5

13.3

82.6

12.3

0.001*

HbA1C (%)

9.2

2.4

9.6

2.7

0.44

BMI (kg/m2)

24.3

4.7

23.3

4.1

0.21

Serum Cholesterol (mg/dL)

191.6

49.0

186.9

49.7

0.62

HDL Cholesterol (mg/dL)

43.2

18.5

41.7

23.2

0.73

Serum Triglyceride (mg/dL)

253.5

167.0

219.6

112.8

0.13

LDL Cholesterol (mg/dL)

138.6

44.1

140.2

42.4

0.84

DM is a complex metabolic disorder, which has emerged not only as a major public health issue around the world but also as a major cause of economic burden worldwide.12 The global incidence of DM is rising at an astonishing rate and this mounting toll of DM related morbidities and mortalities is posing a serious threat to the developing as well as developed world.13 The complications related to the disease are affecting masses not only socially but also economically. While the complications related to DM are further imposing economic burden on the country and specifically the common man. Proper knowledge about the incidence rate of these DM related complications as well as early diagnosis and possible strategies to treat these complications is the need of the hour for developing and developed countries alike.14,15
The findings of this study provided a potential insight of the prevalence of complications and their risk factors in the type 2 DM patients of Sindh. Our study findings strongly suggest that there is an association between DM and chronic macro vascular complications. The overall prevalence of macro vascular complications among our study population with type 2 DM was 28.5%. In comparison to previous studies, rising trends in the prevalence of complications were observed. A study conducted in Punjab, Pakistan by Gillani et al.16 reported the prevalence of macro vascular complication in their study was 21.7%. While a study by Li J. et al. reported that comparable proportion of their participants with DMT2 were having macro vascular complication.17 A study from Saudi Arabia reported 12.1% of total macro vascular diseases among their diabetic participants that is quite lower than our study.18 In the present study, among the patients of macro vascular complication, 16.7% had CADs, 6.5% had CVD and 5.3% had PVD. Several studies also reported similar trend of macro vascular complications as demonstrated in this study. Alaboud et al. reported the consistent findings of macro vascular complications in their study participants. Another study by Gedebjerg et al. also reported higher prevalence (15%) of CADs in their patients followed by 5% CVDs and 2% PVDs in their study. Moreover, Uddin et al. reported prevalence of 8.5% CADs, 2.0% CVD and 2.2% PVD in their newly diagnosed diabetics patients.19
The risk factors analysis in the present study demonstrated that duration of DM was the main risk factor (p<0.05) for CAD and PVD but not for CVD while systolic hypertension was the risk factor common (p<0.05) in CAD, PVD and CVD. Ahmed M.S et al also reported the findings consistent with our study.20 Moreover, age and diastolic blood pressure were significantly associated with CAD and CVD, but not PVD. A Pakistani study by Gillani et al. reported the strong association between age and CAD, which is consistent with the findings of present study.16 Serum triglycerides was a common significantly associated (p<0.05) factor of CAD and PVD in this study. This may be due to fact that high serum triglycerides may lead to increase chances of thrombus formation within the vessels and lead to blockage of blood circulation in the vessels. With strengths, there are many limitations in the study. Foremost, limited duration and resources only one center was included in the study. Furthermore, only macro vascular complications were studied in the present study while many risk factors like economic status, treatment etc. are not included for the study.

The CAD seem to be the most common macro vascular complication among type 2 diabetic patients, with a high prevalence of risk factors such as advanced age, duration of DM, male sex, hypertension, BMI, and serum triglycerides.

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