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TAE0010.1177/2042018817692296Therapeutic Advances in Endocrinology and MetabolismA Hussain, I Ali

Therapeutic Advances in Endocrinology and Metabolism Original Research

Correlation between hemoglobin A1c and


Ther Adv Endocrinol
Metab

serum lipid profile in Afghani patients


2017, Vol. 8(4) 51­–57

DOI: 10.1177/
https://doi.org/10.1177/2042018817692296
https://doi.org/10.1177/2042018817692296
2042018817692296

with type 2 diabetes: hemoglobin A1c © The Author(s), 2017.


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prognosticates dyslipidemia
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Arshad Hussain, Iftikhar Ali, Muhammad Ijaz and Afaq Rahim

Abstract
Background: Patients with type 2 diabetes (T2DM) have an increased prevalence of
dyslipidemia, which contributes to their high risk of cardiovascular diseases (CVDs). This study
is an attempt to determine the correlation between hemoglobin A1c (HbA1c) and serum lipid
profile and to evaluate the importance of HbA1c as an indicator of dyslipidemia in Afghani
patients with T2DM.
Methods: A total of 401 Afghani patients with T2DM (men, 175; women, 226; mean age,
51.29 years) were included in this study. The whole blood and sera were analyzed for fasting
blood sugar (FBS), HbA1c, total cholesterol (TC), triglycerides (TGs), high-density lipoprotein
cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Dyslipidemia was
defined according to the National Cholesterol Education Program Adult Treatment Panel III
(NCEP ATP III) guidelines. Diabetes was defined as per American Diabetes Association criteria.
The correlation of FBS, HbA1c with lipid ratios and individual lipid indexes were analyzed. The
statistical analysis was done by SPSS statistical package version 16.0.
Results: The mean age ± standard deviation of male and female patients were 51.71 ± 11.70
and 50.97 ± 10.23 years respectively. There was a significant positive correlation between
HbA1c, TC, TG, LDL-C and LDL-C/HDL-C ratio. The correlation between HbA1c and HDL-C
was negative and was statistically nonsignificant. Furthermore, HbA1c was found to be a
predictor of hypercholesterolemia, LDL-C and TG via a linear regression analysis. Patients
with HbA1c value greater than 7.0% had significantly higher value of cholesterol, LDL-C, and
LDL-C/HDL-C ratio compared with patients with an HbA1c value up to 7.0%.
Conclusions: Apart from a reliable glycemic index, HbA1c can also be used as a predictor of
dyslipidemia and thus early diagnosis of dyslipidemia can be used as a preventive measure for
the development of CVD in patients with T2DM.
Correspondence to:
Keywords:  Afghanistan, cardiovascular diseases, diabetes mellitus, dyslipidemia, HbA1c, Iftikhar Ali
Department of Pharmacy,
serum lipids University of Swabi, 23430,
Khyber Pakhtunkhwa,
Pakistan
Received: 3 November 2016; accepted in revised form: 13 January 2017. Department of Pharmacy
Services, Northwest
General Hospital &
Research Center,
Peshawar 25100, Khyber
Introduction T2DM is a rapidly growing public health Pakhtunkhwa, Pakistan
iftikharalijan@gmail.com
Diabetes mellitus (DM) is a chronic metabolic problem worldwide, with a significant impact on
Arshad Hussain,
disorder that occurs as a result of a complex inter- health, quality of life and the healthcare system of Muhammad Ijaz,
action of genetic, environmental factors, and life- the countries. According to current statistics from Afaq Rahim
Department of Medicine &
style choices. Morbidity and mortality due to DM the International Diabetes Federation (IDF), 415 Allied, Northwest General
are increasing because of changes in behavior million adults have DM worldwide; this figure is Hospital & Research
Center, Peshawar 25100,
such as an unhealthy diet, physical inactivity, expected to reach the 642 million mark by 2040, Khyber Pakhtunkhwa,
being overweight, obesity and tobacco use.1,2 which means every 11th individual will be Pakistan

journals.sagepub.com/home/tae 51
Therapeutic Advances in Endocrinology and Metabolism 8(4)

diagnosed as having T2DM.3 The proportion of the diabetic population. This positive correlation
people with T2DM is increasing in most coun- between HbA1c and CVD has been demon-
tries.3 Nearly 80% of people with the disease live strated in nondiabetic cases, even within the nor-
in low- and middle-income countries.4 mal range of HbA1c.7,11

Pakistan and Afghanistan have been included in The aim of this study was to assess the relationship
the Middle East and North African region by the between glycemic control (HbA1c) and serum
IDF; this region is approximately 9.7% of the lipid profile as well as to evaluate the importance of
total regional population, which means around HbA1c as an indicator of dyslipidemia in patients
37 million people in the region are living with with T2DM in an Afghani population.
T2DM.5

Due to the political instability in Afghanistan, very Material and methods


limited data are available regarding the prevalence
of DM in the country, its complications and mor- Study design and location
tality rates. The prevalence of DM in the adult A cross-sectional study was conducted from April
population after the world population adjustment 2015 to August 2015. Afghani patients with
has been estimated to be 8.6% and 9.9% in 2010 T2DM visiting an outpatient department (dia-
and 2030 respectively.1,6 betic clinic) in the Northwest General Hospital &
Research Center, Hayatabad Peshawar, Khyber
Annually, 5% of all deaths globally are related to Pakhtunkhwa, Pakistan were included in the
DM and its complications.7 DM was responsible study. This is a 220-bed tertiary care hospital, a
for 342,000 deaths in 2015 in this part of the Venture of Alliance Healthcare (PVT) Ltd,
world.5 Over half (51.3%) of all deaths from DM located in the historic city of Peshawar. Its catch-
in the region occurred in people under 60 years of ment area is all over the province of Khyber
age. These early deaths may be the result of a Pakhtunkhwa and nearby border areas of
combination of factors: the rapidly changing envi- Afghanistan. The study protocol was approved by
ronments and lifestyles in the region, late diagno- the ethics committee of the Hospital. Informed
ses, and healthcare systems that are not equipped written consent was obtained from all the patients
to provide optimal management of the increasing after explaining the study objectives.
numbers of people with DM.8

DM is a metabolic disorder that has a long-term Patients and methods


impact on different body systems, contributing to Venous blood samples were collected from a total
the huge burden of morbidity associated with it. of 401 Afghani patients with T2DM, of which
Cardiovascular disease (CVD) is one group there were 175 men and 226 women. The serum
among the spectrum of diseases; altered lipid was used for analyzing fasting blood sugar (FBS),
metabolism in DM contributes to atherosclero- total cholesterol (TC), high-density lipoprotein
sis.9 This greatly increases the risk of CVD com- cholesterol (HDL-C), triglycerides (TGs), and
pared with people without DM. The prevalence low-density lipoprotein cholesterol (LDL-C)
of CVD is higher in people with T2DM and is using an auto analyzer (Roche/Hitachi 912/
also the top killer in this population.4 Modular Analyzers: CAN 435, Germany).
HbA1c was estimated using an ARCHITECT
DM is an independent risk factor for CVD and c4000 analyzer (Abbott Diagnostics, USA).
it potentiates the effects of other common risk
factors such as smoking, hypertension and For the serum lipid reference level, the National
dyslipidemia.10 Cholesterol Education Program Adult Treatment
Panel III (NCEP ATP III) guideline was referred.
HbA1c predicts the risk of developing diabetic According to these guidelines, hypercholester-
complications in patients with DM.7 Apart from olemia is defined as TC greater than 200 mg/dl,
classical risk factors like dyslipidemia, elevated high LDL-C when the value is over 100 mg/dl,
HbA1c is an independent risk factor for CVD. It hypertriglyceridemia when TG is greater than
is estimated that there is an 18% increased risk of 150 mg/dl and low HDL-C as a value less than 40
CVD for each 1% rise in absolute HbA1c levels in mg/dl. Dyslipidemia was defined as the presence

52 journals.sagepub.com/home/tae
A Hussain, I Ali et al.

Table 1.  Serum lipid profile parameter results for male and female patients with T2DM.

Parameters Male patients (n = 175) Female patients (n = 226) p value

  Mean SD Range Mean SD Range


Age (years) 51.71 11.70 22–92 50.97 10.23 17–81 0.49
FBS (mg/dl) 219.64 96.52 95–580 239.15 103.18 95–500 0.07
HbA1c (%) 9.79 2.66 5.50–16.80 9.94 2.36 5.50–16.50 0.53
Cholesterol (mg/dl) 204.08 54.46 88–365 208.04 52.96 96–321 0.46
TG (mg/dl) 266.03 156.72 51–1046 249.53 131.79 45–779 0.25
HDL-C (mg/dl) 39.68 14.25 13–98 41.75 13.08 18–98 0.13
LDL-C (mg/dl) 115.10 55.35 20–295 121.67 48.77 23–256 0.20
TC/HDL-C 5.64 2.21 1.70–15.38 5.40 2.03 1.59–15.45 0.27
FBS, fasting blood sugar; HbA1c, hemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density
lipoprotein cholesterol SD, standard deviation; T2DM, type 2 diabetes mellitus; TC, total cholesterol; TG, triglyceride.

of one or more abnormal serum lipid concentra- less than 40 mg/dl in 51.9% of the study sample.
tions.12 DM was defined as per American Diabetes Of the 401 patients, 48 (11.97%) had only one
Association criteria.13 abnormal lipid profile parameter, 44 (10.97%) had
two abnormal lipid parameters, and 208 (51.87%)
All patients were categorized into two groups had more than two abnormal lipid profile param-
according to their HbA1c levels. The data were eters. According to the NCEP ATP III guideline,
evaluated via the SPSS statistical package version 118 of 226 women (52.21%) and 83 of 175 men
16.0. Pearson’s correlation test was performed to (47.42 %) were found to have dyslipidemia.
examine various correlations. Independent sam-
ple Student’s t test (two tailed) was used to com- The mean value of FBS, HbA1c, TC, HDL-C
pare means of different parameters. All p values and LDL-C were slightly higher in female com-
less than 0.05 were considered statistically signifi- pared with male patients, but the differences
cant. The value of HbA1c was given as a percent- were not statistically significant. Although the
age of the total hemoglobin and values of all other mean levels of TC and the TC/HDL-C ratio
parameters were given in mg/dl. All values are were slightly lower in women than in men, these
expressed as mean ± standard deviation (SD) or differences were statistically nonsignificant, as
standard error of the mean. shown in Table 1.

The age and FBS of patients did not show any


Results significant correlation with HbA1c (r = 0.063, p
A total of 401 Afghani patients with T2DM = 0.206; r = 0.098, p = 0.072 respectively).
(men, 175; Women; 226; mean age, 51.29 years) There was a significant positive correlation
were included in this study. The mean age ± SD between HbA1c and TC (r = 0.257, p = 0.000).
of male and female patients were 51.71 ± 11.70 HbA1c also demonstrated a significant correla-
and 50.97 ± 10.23 years respectively. The mean tion with TG (r = 0.235, p = 0.000). The corre-
± SD of FBS, HbA1c, TC, TG, HDL-C and lation between HbA1c and HDL-C was negative
LDL-C were 230.54 ± 100.58, 9.84 ± 2.47, 206 and was found to be statistically nonsignificant (r
± 53.51, 256 ± 143.2, 40.85 ± 13.62, and 118.81 = −0.024, p = 0.625). Furthermore, it was found
± 51.78 respectively. that HbA1c was positively and significantly
related to LDL-C (r = 0.153, p = 0.002) and
Hypercholesterolemia was found in 50.1% of LDL-C/HDL-C ratio (r = 0.150, p = 0.003).
patients; similarly hypertriglyceridemia was found HbA1c was also found to be a predictor of hyper-
in 74.8% of patients. Abnormal LDL-C levels cholesterolemia (p = 0.000, R2 = 0.078), LDL-C
were found in 62.8% of patients and HDL-C was (p = 0.002, R2 = 0.002), and TG (p = 0.000,

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Therapeutic Advances in Endocrinology and Metabolism 8(4)

Figure 1.  Correlations between hemoglobin A1c, FBS and lipid profile panel. FBS, fasting blood sugar;
HDL, high-density lipoprotein; LDL, low-density lipoprotein; TC, total cholesterol; TG, triglyceride.

R2 = 0.055) validated by a linear regression 7.0% and the second group consisted of patients
analysis as shown in Figure 1. However, HDL-C with HbA1c values greater than 7.0%. Patients
(p = 0.625, R2 = 0.001) and FBS (p = 0.963, with HbA1c values greater than 7.0% had
R2 = 0.000) did not show any significant associa- significantly higher values of cholesterol
tion with HbA1c in the regression analysis. (p = 0.004), LDL-C (p = 0.002), LDL-C/
HDL-C ratio (p = 0.024), FBS (p = 0.64), TG
Patients were divided into two groups as per (p = 0.097), HDL-C (p = 0.334), and risk ratio
their glycemic index (HbA1c); the first group (p = 0.58), compared with the first group, as
consisted of patients with HbA1c values up to shown in Table 2.

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A Hussain, I Ali et al.

Table 2.  Biochemical parameters categorized by patient’s hemoglobin A1c.

Parameters HbA1c ⩽ 7.0(n = 66) HbA1c > 7.0 (n = 335) p value

  Mean SD Range SEM Mean Range SD SEM


Age (years) 49.39 13.18 17–81 1.62 51.67 19–92 10.36 0.57 0.12
FBS (mg/dl) 224.4 88.77 95–400 12.31 231.35 95–560 102.62 6.05 0.64
Cholesterol (mg/dl) 189.03 46.12 102–318 5.68 209.72 88–365 54.36 2.97 0.004*
TG (mg/dl) 229.97 144.04 69–654 17.73 262.00 45–1046 142.72 7.79 0.097
HDL-C (mg/dl) 39.36 15.25 13–93 1.85 41.14 18–98 13.34 0.73 0.334
LDL-C (mg/dl) 101.08 47.19 35–240 5.81 122.30 20–295 51.99 2.84 0.002*
TC/HDL- C (risk ratio) 5.37 2.32 1.59–15.38 0.29 5.53 1.65–15.45 2.07 0.11 0.58
LDL-C/HDL-C 2.76 1.23 0.39–4.70 0.15 3.21 0.33–9.90 1.53 0.08 0.024*
*Statistically significant.
FBS, fasting blood sugar; HbA1c, hemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol SD,
standard deviation; SEM, standard error of the mean; TC, total cholesterol; TG, triglyceride.

Discussion In one Pakistani study by Firdous and colleagues,


The association of DM and CVD is well known 38% of people with DM were found to have high
and this relationship has been much discussed over TG levels. In our study, women with DM were
the past few decades.14 Both lipid profile and DM found to have slightly higher LDL levels com-
have been shown to be important predictors of pared with men, which is consistent with previous
metabolic disturbances, including dyslipidemia, studies.7,12,22
hypertension, CVD, and hyperinsulinemia.15
It is suggested that insulin resistance has a cen-
People with T2DM have a higher cardiovascular tral role in the development of diabetic dyslipi-
morbidity and mortality, and are disproportion- demia. One of the causes is increased free fatty
ately affected by CVD compared with subjects acid release from insulin-resistant fat cells.23
without DM. Early detection and treatment of If the glycogen stores are adequate, these free
dyslipidemia associated with DM may be one fatty acids promote TG production which
step in reducing the CVD risk.16 further stimulates Apolipoprotein (Apo-B) and
very low density lipoprotein.24
In our study, the correlation of HbA1c and lipid
profile in T2DM was evaluated. Interestingly, According to the Diabetes Complications and
52.21% of women and 47.42% of men were found Control Trial, HbA1c is the gold standard of gly-
to have dyslipidemia according to the NCEP ATP cemic control.25 Various studies have shown an
III guideline. These findings are consistent with HbA1c of up to 7.0% may reduce the risk of car-
some previous studies.7,12,13,17 Hyperlipidemia in diovascular complications.7,11
women may be attributed to the effects of sex hor-
mones on body fat distribution, which leads to dif- In our study, we divided patients into two groups
ferences in changed lipoproteins.18 as per the HbA1c values. Those with HbA1c
greater than 7.0% exhibited a significant increase
We observed that the correlation between HbA1c in TC, LDL-C, TG, and LDL-C/HDL-C ratio
and HDL-C was negative, however there was a compared with those with HbA1c up to 7.0%.
positive, significant correlation between HbA1c Improving glycemic control may substantially
and TC, LDL-C, and TGs. Various studies have reduce the risk of cardiovascular events. It has
described this before.7,19–21 been projected that a decrease in the HbA1c value
by 0.2% could lower the mortality by 10%.26
A rather interesting finding was that HbA1c was
found to be a predictor of hypercholesterolemia The results of our study suggest the importance
by linear regression analysis. of glycemic control in managing dyslipidemia and

journals.sagepub.com/home/tae 55
Therapeutic Advances in Endocrinology and Metabolism 8(4)

further reducing the risk for CVD in patients with Conflict of interest statement
T2DM, as shown by the significant association of The authors declare that there is no conflict of
HbA1c with various lipid parameters. interest.

Data from the Afghani population are lacking due


to political unrest in the form of war and a paucity References
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