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Dyslipidemia Pattern Among Newly Diagnosed and Known Type 2 Diabetics: A Comparative Analysis from a Tertiary Care Hospital of Karachi, Pakistan.

Byline: Nadeem Naeem, Anum Butt, Awn Bin Zafar, Asher Fawwad, Bilal Tahir and Abdul Basit

Key words: Dyslipidemia, diabetes, hyperglycemia, Pakistani population.

Introduction

Diabetes mellitus has become one of the most prevalent non communicable disease with rapid rise in numbers globally.1 International Diabetes Federation (IDF) Atlas in 2017 reported a prevalence of diabetes as 8.8% around the globe.2

Basit et al., reported 26.3% overall weighted prevalence of diabetes in Pakistan in 2018.3 Numerous studies have demonstrated that the traditional risk factors for cardiovascular disease including hypertension, cigarette smoking, and lipid abnormalities play an important role in development of complications in subjects with diabetes.4,5 Subjects with type 2 diabetes mellitus affected with macro vascular complications including dyslipidemia suffer 1.5 to 3.6 fold increase in mortality.6,7 According to the World Health organization (WHO), the prevalence of dyslipidemia is 30.3% in the region of South East Asia, 36.7% in Western Pacific, 53.7% in Europe and 47.7% in America.8 In general population various types of dyslipidemias were identified in diabetes mellitus.

Dyslipidemia includes increased total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C).9 Globally the prevalence of hyper-cholesterolemia among adults is 37% for males and 40% for females.10 Frequency of dyslipidemia is on continuous rise in the developing countries including Pakistan.11 This trend is mostly attributed to unhealthy dietary patterns, obesity, tobacco use, alcohol abuse, reduced physical activity, aging of population and many other co-factors.9 These behavioral risk factors were responsible for 80% of coronary heart disease and cerebro vascular disease.12 People with type 2 diabetes showed 2-4 fold increased risk for coronary artery disease due to increase in multiple risk factors and dyslipidemia is one of them.13

Many epidemiological studies have proven that increased LDL cholesterol and non-HDL cholesterol levels and decreased HDL cholesterol levels are associated with an increased risk of cardiovascular disease in individuals with diabetes.14,15

There is immense need of public health measures targeting dyslipidemia and treating individuals especially with added risk factors like obesity, physical inactivity, tobacco use, diabetes mellitus and hypertension.16 In this regard, the current study was conducted to compare the pattern of dyslipidemia in newly diagnosed and known type 2 diabetics in our local population.

Methodology

This retrospective study was conducted at Baqai institute of Diabetology and Endocrinology and Baqai Medical University, (BMU), a tertiary care unit in Karachi-Pakistan.The duration of study was from January 2005 to May 2016. Known type 2 diabetes mellitus and newly diagnosed type 2 diabetes mellitus patients were included and those with gestational diabetes and type 1 diabetes were excluded. Ethical approval was obtained by Institutional Review Board (IRB) of BIDE. Medical records were obtained from computerized hospital management system (HMS).

Biochemical parameters were measured by standard laboratory test methods. Hyper-cholesterolemia was defined as cholesterol over 200 mg/dl. A triglyceride >150mg/dl was considered to be hyper-triglyceridemia. LDL cholesterol concentration was stated to be abnormal if it was >100 mg/dl. Low HDL was <40 mg/dl for male and 7% were taken as good and poor control respectively.19

Table 1: Anthropometric and clinical characteristics of studied individuals.

###Diabetes status###Dyslipidemia

Parameters###Overall###Newly###Known DM###p-value###No###Yes###p-value

###Diagnosed DM

n###12256###2091###10165###-###2025###10231###-

Age (years)###52.46+-10.94###48.39+-11.45###53.3+-10.64###<0.0001###54.43+-11.25###52.07+-10.84###<0.0001

Gender###Male###7073 (57.7%)###1277 (61.1%)###5796 (57%)###0.001###1391 (68.7%)###5682 (55.5%) <0.0001

###Female###5183 (42.3%)###814( 38.9%)###4369 (43%)###634 (31.3%)###4549 (44.5%)

Marital###Single###600 (6.2%)###118 (6.7%)###482 (6%)###0.296###91 (6.3%)###509 (6.1%)###0.769

status###Married###9153 (93.8%)###1645 (93.3%)###7508 (94%)###1348 (93.7%)###7805 (93.9%)

Weight (kg)###73.78+-15.26###76.25+-16.39###73.21+-14.94###<0.0001###72.56+-14.82###74+-15.34###0.001

Height (cm)###161.44+-9.6###162.25+-9.61###161.25+-9.59###<0.0001###162.42+-9.14###161.26+-9.68###<0.0001

Body mass index###28.35+-5.49###29+-5.79###28.2+-5.41###<0.0001###27.55+-5.37###28.5+-5.5###<0.0001

(kg/m2)

Systolic blood###130.16+-19.77###125.78+-18.16###131.13+-19.99###<0.0001###129.45+-19.92###130.29+-19.75###0.121

pressure (mmHg)

Diastolic blood###81.03+-10.28###81.07+-10.24###81.02+-10.29###0.869###80.33+-10.23###81.16+-10.29###0.004

pressure (mmHg)

Smoking###No###9223 (90%)###1637 (88.4%)###7586 (90.4%)###0.012###1420 (90.4%)###7803 (89.9%)###0.545

Habit###Yes###1022 (10%)###214 (11.6%)###808 (9.6%)###150 (9.6%)###872 (10.1%)

Family###No###3153 (30.8%)###609 (33%)###2544 (30.3%)###0.022###503 (32%)###2650 (30.6%)###0.249

history###Yes###7083 (69.2%)###1235 (67%)###5848 (69.7%)###1067 (68%)###6016 (69.4%)

of DM

HTN###No###4105 (40.4%)###904 (49.2%)###3201 (38.5%)###<0.0001###664 (42.4%)###3441 (40.1%)###0.081

###Yes###6047 (59.6%)###934 (50.8%)###5113 (61.5%)###901 (57.6%)###5146 (59.9%)

Obesity###No###2696 (28.2%)###433 (24.2%)###2263 (29.2%)###<0.0001###525 (35%)###2171 (27%)###<0.0001

###Yes###6856 (71.8%)###1356 (75.8%)###5500 (70.8%)###974 (65%)###5882 (73%)

HbA1c (%)###9.41+-2.25###9.2+-2.45###9.46+-2.2###<0.0001###8.92+-2.12###9.5+-2.26###<0.0001

Serum creatinine (mg/dl)###1.11+-0.94###0.99+-0.44###1.13+-1.01###<0.0001###1.07+-0.51###1.11+-1###0.091

Table 2 The serum lipid concentrations and frequency of dyslipidemia by diabetes status.

Parameters###Newly diagnosed DM (n)###Known DM###p-value###Overall (n)

###2091###10165###-###12256

Cholesterol (mg/dl)###185.75+-48.19###175.63+-48.45###<0.0001###177.36+-48.55

Triglyceride (mg/dl)###180.93+-148.19###175.43+-134.35###0.001###176.36+-136.79

HDL (mg/dl)###38.03+-9.3###37.38+-9.73###0.009###37.49+-9.66

LDL (mg/dl)###114.11+-35.61###105.88+-36.72###<0.0001###107.27+-36.67

Hyper-cholesterolemia###669 (33.2%)###2725 (27.7%)###<0.0001###3394 (28.7%)

Hyper-triglyceridemia###937 (49.7%)###4343 (46.7%)###0.017###5280 (47.2%)

Low HDL cholesterol###1356 (73.9%)###6922 (76%)###0.049###8278 (75.7%)

High LDL cholesterol###604 (31.7%)###2310 (24.6%)###<0.0001###2914 (25.8%)

Dyslipidemia###1745 (83.5%)###8486 (83.5%)###0.973###10231 (83.5%)

Results

From the 12256 participants involved in the study, 57.7% were male and the rest were female. Mean age was 52.46+-10.94%. Mean body mass index (BMI) was 28.35+-5.49, 29+-5.79 in newly diagnosed individuals and 28.2+-5.41 in individuals with known diabetes. Around 60%of the participants were found to be hypertensive, prevalence of hypertension was 50.8% in individuals with newly diagnosed diabetes and 61.5% in known diabetes group. Mean obesity was found in 71.8% of the participants. Newly diagnosed diabetes group showing higher prevalence of obesity 1356 (75.8%) as compared to known diabetes group 5500 (70.8%). Dyslipidemia was found in 83.5% of individuals with both groups sharing the exact same prevalence of 83.5%, and has shown significant association with age, gender, height, BMI, obesity and HbA1c (p <0.0001) (Table-1).

Table-2 represents the lipid level and frequency of dyslipidemia in newly diagnosed and known diabetes mellitus. Overall frequency of dyslipidemia was found 83.5% in both groups. In individual with newly diagnosed diabetes mellitus frequency of hyper-cholesterolemia, hyper-triglyceridemia, low HDL and high LDL were 33.2%, 49.7%, 73.9% and 31.7% respectively. While in known diabetes mellitus group same frequencies were 27.7%, 46.7%, 76% and 24.6% respectively.

As shown in Figure, significant differences were found in different age groups (p <0.05), the peak prevalence of dyslipidemia in both groups was between 30-39 years, and then declined gradually. Frequency of dyslipidemia was significantly higher in known diabetes mellitus group between age 50 - 59 years.

Table 3: Dyslipidemia according to comorbidities.

Comorbidity###Hypercholesterolemia###Hypertriglyceridemia Low HDL###High LDL###Dyslipidemia

Newly diagnosed DM###669 (33.2%)###937 (49.7%)###1356 (73.9%)###604 (31.7%)###1745 (83.5%)

Known DM###2725 (27.7%)###4343 (46.7%)###6922 (76%)###2310 (24.6%)###8486 (83.5%)

O.R (95% CI)###0.77 (0.69-0.85)###0.88 (0.80-0.97)###1.12 (1.0-1.25)###0.70 (0.63-0.78)###1.0 (0.88-1.13)

p-value###<0.0001###0.017###0.049###0.702###0.973

Non-hypertensive###1094 (27.7%)###1720 (45.4%)###2817 (75.8%)###995 (25.8%)###3441 (83.8%)

Hypertensive###1712 (29.2%)###2636 (47.4%)###4226 (77.5%)###1479 (26.3%)###5146 (85.1%)

O.R (95% CI)###1.07 (0.98-1.18)###1.08 (1.0-1.18)###1.09 (0.99-1.21)###1.02 (0.93-1.12)###1.10 (0.98-1.22)

p-value###0.097###0.051###0.063###0.62###0.081

Non-obese###677 (26%)###959 (38.6%)###1764 (72.3%)###637 (25.2%)###2171 (80.5%)

Obese###2048 (31%)###3248 (51.6%)###4787 (77.6%)###1763 (27.7%)###5882 (85.8%)

O.R (95% CI)###1.27 (1.15-1.41)###1.69 (1.53-1.86)###1.32 (1.19-1.47)###1.13 (1.01-1.25)###1.46 (1.29-1.64)

p-value###<0.0001###<0.0001###<0.0001###0.021###<0.0001

Table 4: Logistics regression analysis for predictors of dyslipidemia.

Lipid/Predictors###Female###Age###Married###Hypertension###Obesity###Smoker###Positive family history

Hyper-###1.22###0.99###1.31###1.04###1.43###0.89###0.96

cholesterolemia###(0.98-1.52)###(0.99-1)###(0.85-2.03)###(0.84-1.28)###(1.11-1.86)###(0.63-1.27)###(0.77-1.2)

p-value###0.077###0.231###0.222###0.73###0.006###0.531###0.719

Hyper-###0.8###0.98###0.98###1.08###1.43###1.32###1

triglyceridemia###(0.64-1)###(0.97-0.99)###(0.63-1.51)###(0.88-1.33)###(1.11-1.83)###(0.94-1.86)###(0.8-1.25)

p-value###0.05###<0.0001###0.917###0.453###0.005###0.114###0.99

###3.42###0.97###1.66###1.07###1.09###1.38###0.89

Low HDL###(2.56-4.58)###(0.96-0.98)###(1-2.76)###(0.84-1.37)###(0.82-1.45)###(0.94-2.04)###(0.68-1.17)

p-value###<0.0001###<0.0001###0.05###0.588###0.547###0.1###0.396

###1.44###0.99###1.17###1.05###1.38###0.8###0.91

High LDL###(1.15-1.81)###(0.98-1)###(0.75-1.83)###(0.84-1.31)###(1.06-1.81)###(0.55-1.18)###(0.72-1.15)

p-value###0.002###0.156###0.496###0.666###0.018###0.262###0.443

###1.43###0.98###1.7###1.26###1.51###0.83###1.07

Dyslipidemia###(1.07-1.93)###(0.97-0.99)###(1.04-2.79)###(0.96-1.66)###(1.12-2.03)###(0.55-1.25)###(0.8-1.43)

p-value###0.017###<0.0001###0.035###0.091###0.006###0.379###0.637

Known DM###Female###Age###Married###Hypertension###Obesity###Smoker###Positive family history

Hyper-###1.48###0.98###1.12###1.16###1.07###1.4###0.96

cholesterolemia###(1.32-1.65)###(0.98-0.99)###(0.89-1.39)###(1.04-1.29)###(0.95-1.21)###(1.17-1.68)###(0.86-1.08)

p-value###<0.0001###<0.0001###0.337###0.01###0.268###<0.0001###0.485

Hyper-###1.21###0.98###0.97###1.17###1.61###1.29###1.09

triglyceridemia###(1.09-1.34)###(0.97-0.98)###(0.79-1.19)###(1.05-1.29)###(1.45-1.8)###(1.09-1.53)###(0.98-1.22)

p-value###<0.0001###<0.0001###0.755###0.003###<0.0001###0.004###0.106

###2.96###0.99###1.22###1.01###1.07###1.28###0.93

Low HDL###(2.58-3.38)###(0.98-0.99)###(0.95-1.57)###(0.9-1.14)###(0.94-1.22)###(1.05-1.56)###(0.82-1.06)

p-value###<0.0001###<0.0001###0.126###0.847###0.321###0.013###0.265

###1.35###0.99###1.06###1.07###0.96###1.21###0.93

High LDL###(1.2-1.51)###(0.98-0.99)###(0.84-1.33)###(0.96-1.2)###(0.84-1.08)###(1-1.46)###(0.83-1.05)

p-value###<0.0001###<0.0001###0.628###0.245###0.458###0.054###0.265

###1.79###0.98###1.12###1.04###1.17###1.44###0.96

Dyslipidemia###(1.55-2.06)###(0.98-0.99)###(0.85-1.47)###(0.91-1.19)###(1.02-1.35)###(1.14-1.83)###(0.83-1.11)

p-value###<0.0001###<0.0001###0.434###0.584###0.026###0.003###0.569

Calculations of the prevalence of dyslipidemia on the basis of co-morbidities, with odds ratios and 95% confidence intervals is reported in Table-3. Among types of dyslipidemia, hyper-cholesterolemia, hyper-triglyceridemia and low HDL were significantly associated with diabetes status and hyper-cholesterolemia, hyper-triglyceridemia, dyslipidemia, high LDL and low HDL was significantly associated with obesity.

A logistic regression analysis was performed for significant predictors (Table-4). Age was a significant predictor for hyper-triglyceridemia, low HDL, and dyslipidemia in individuals with newly diagnosed diabetes mellitus and all types of dyslipidemias in individuals with known diabetes mellitus. Female gender was a significant predictor for all types of dyslipidemias in known diabetes mellitus group while in newly diagnosed diabetes mellitus group low HDL, high LDL, hyper-triglyceridemia and dyslipidemia were significantly associated with female gender.

Obesity was found significant for all types of dyslipidemias except low HDL in newly diagnosed and all except hyper-cholesterolemia, low HDL and high LDL in individuals with known diabetes mellitus. Smoking was found significantly associated with all types of dyslipidemias except high LDL in individuals with known diabetes mellitus and was not associated with any dyslipidemia significantly in newly diagnosed group.

Data analysis were perform using SPSS version 20. T-test or Mann Whitney test were used as appropriate after checking for normality. Multiple logistic regression for significant predictors were performed. Level of significance was set to be <0.05. Total frequency in some columns may vary due to missing data from certain variables.

Discussion

An important and alarming finding of our study is that, the frequency of dyslipidemia was found in more than eighty percent of diabetic individuals which was higher than the similar type of studies done on diabetic population in India1 and much higher than the normal and pre diabetic population of Asia.20 Though significant association of dyslipidemia with age, gender, height, HbA1c, obesity and BMI was the finding which is in consensus with same study of India. Elevated LDL being major risk factor for cardiovascular disease21 was one of the most important type of dyslipidemia tested in our study and it showed that 25.8% of the subjects had raised LDL levels as compared to 83.5% frequency of overall dyslipidemia. These results were comparable to the data from Kennady et al.,22 who found that 45% of those with diabetic dyslipidemia have their LDL within target range.

Another important finding shared by both groups is low HDL being the most common type of dyslipidemia in diabetic population which is in correspondence with results obtained by Singh et al. in 2015 showing that HDL-Cholesterol was significantly lower in diabetic subjects.23

Furthermore, a significant influence of age on dyslipidemia with highest frequency between 30-39 and declined at [greater than or equal to]60 are the findings which were comparable with previous study reported dyslipidemia peaking at 30 to 39.24

Khaderet al reported a higher frequency of raised triglycerides and total cholesterol levels and low HDL levels in overweight and obese subjects in Arab population.25 Our study reported similar type of findings with hyper-triglyceridemia, hyper-cholesterolemia, low HDL and dyslipidemia being significantly associated with obesity.

A study published in 2008 from Pakistan showed that 41.2% of the study participants have got raised LDL levels26 which was significantly higher than the frequency of raised LDL levels in this study. This finding may be highlighting the gradual improvement in the health care system of the country. An alarming finding of our study is the same frequency of dyslipidemia in newly diagnosed and known diabetes mellitus group, emphasizing the need to target the cholesterol levels as soon as diabetes mellitus is diagnosed.

We conclude that majority of the diabetics were either newly diagnosed or known have disturbed lipid parameters. Specifically, the pattern in newly diagnosed subject was alarmingly high. Further larger scale community-based studies are required to ascertain the findings of this study.

Diabetes as a cardiovascular risk equivalent with very high mortality and morbidity reported leading to macrovascular complications, it would be pertinent to check lipid profile for every type 2 diabetic patient at the time of first reporting and then annually. Early screening and effective management can improve secondary prevention level.

Conflict of interest: None declared.

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Author:Nadeem Naeem, Anum Butt, Awn Bin Zafar, Asher Fawwad, Bilal Tahir and Abdul Basit
Publication:Pakistan Journal of Medical Research
Geographic Code:9PAKI
Date:Jun 30, 2020
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