Background: Dyslipidemia is more common in individuals with type 2 diabetes (T2DM), increasing their susceptibility to cardiovascular diseases (CVDs). This study aims to investigate the association between serum lipid profile and hemoglobin A1c (HbA1c), and the significance of HbA1c as a marker of dyslipidemia in T2DM. Method: A retrospective cross-sectional study enrolled 500 patients from the Center of Diabetes and Endocrine Glands in Karbala, Iraq. Participants were selected if they had regular visits with their doctors and up-to-date data in the system. Results: Among the participants, 230 (46.0%) were male and 270 (54.01%) were female, with an age range of 40-49 years representing the highest proportion (36.8%). Out of the participants, 278 (55.6%) had severely elevated HbA1c (=10%), and half of them had moderately elevated (250-299 mg/dL) random blood sugar levels. Among the total participants, 98 (42.6%) were males, with 36 (15.7%) of them being 50 years old or older. Among females, a total of 86 (31.9%) were within the age range of 40-49 years. Regarding marital status, 33 (46.5%) were single, out of which 17 (23.9%) were within the age range of 20-29 years. Among the married participants (151 in total, representing 35.5% of the total), the majority (53, 12.5% of the married participants) were aged 50 or older. Conclusion: HbA1c exhibits a direct and significant correlation with total cholesterol within the lipid profile.
Diabetes mellitus is a chronic metabolic disorder with significant social, health, and economic implications. It is estimated that this condition affected around 285 million individuals globally in 2010, constituting roughly 6.4% of the adult population [1].
The underlying feature common to all types of diabetes is the malfunction or loss of pancreatic beta-cells. Since beta-cells are not regenerated by the human pancreas after the age of 30, any loss of these cells is not replaced. Proposed pathogenetic mechanisms can be categorized into three main groups: disturbances in polyol (e.g., sorbitol) metabolism linked to glucose [2], endothelial abnormalities and excessive protein glycation in various vascular processes [3], and additional processes such as hyperfiltration, intrarenal hypertension, and genetic influences [4].
The two main types of diabetes are T1DM, which is the predominant type in childhood and accounts for 85% or more of diabetes cases in individuals under 20 worldwide, and T2DM, which makes up 5%-10% of all diabetes cases [5, 6]. Lipoproteins are intricate particles comprising a hydrophobic core of non-polar lipids (primarily cholesterol esters and triglycerides), enveloped by a hydrophilic membrane of phospholipids, free cholesterol, and apolipoproteins. These lipoproteins are classified into seven types based on their size, lipid composition, and apolipoproteins [7].
Due to the insolubility of triglycerides and cholesterol in water, they require transport alongside proteins. Apolipoproteins, free cholesterol, phospholipids, and apolipoproteins envelop the central core of lipoproteins, which consists of triglycerides and cholesterol esters, aiding in lipoprotein formation and function.
Hypertriglyceridemia and elevated low-density lipoprotein levels are the most common lipid disorders. While glycemic control can often rectify these abnormalities in T1DM, T2DM often displays lipid anomalies even with improved glycemic control. Thus, testing for dyslipidemia in diabetes patients is recommended. Target triglyceride levels are =200 mg/dL, and low-density lipoprotein cholesterol should be =130 mg/dL [8]. The efficacy of reducing low-density lipoprotein cholesterol to prevent coronary artery disease-related mortality has been demonstrated in various secondary prevention trials that included participants with diabetes [9].
This retrospective longitudinal study was conducted at Al-Zahrawi University College in Karbala, Iraq, and received approval from the center for diabetes and endocrine glands, Karbala, Iraq (Reference No. 02-2021). The study enrolled 500 patients from the center of diabetes and endocrine glands, Karbala, Iraq. Data were collected from September to December 2022 to assess the prevalence of dyslipidemia in DM patients. All participants provided written informed consent, which was documented and maintained.
Demographic data such as age, education level, chronic diseases, and socioeconomic status were obtained from the records, along with biochemical data including FPG, RBS, HbA1c, and lipid profiles. Patients were selected for the study if they were regular visitors to their doctors and had up-to-date data in the system.
Patients using lipid-lowering medications, having cardiovascular diseases, thyroid disorders, renal problems, or other endocrinopathies were excluded. Participants were chosen from those attending the center’s outpatient department and were of both genders. Among those who met the inclusion criteria, 206 individuals’ information was recorded regarding T2DM symptoms, complications, treatment, smoking habits, substance use, and any other addictions. Sample size was calculated using OpenEpi version 3 with the formula \[n=[DEFF\times Np(1-p)]/[(d2/Z21-a/2\times (N-1)+p\times (1-p)]\] yielding a calculated sample size of 500.
In this study, 500 participants were included, with 230 (46.0%) being male and 270 (54.01%) being female. The age range of the participants was 40-49 years (36.8% and SEM = 0.49), which was significantly higher (p<0.05) than other age groups. There was a significant difference (p<0.05) in educational levels, with 31% (SEM = 0.022) of the participants having a university education. Marital status analysis indicated that 425 (85.0%) of the participants were married (SEM = 0.017). Refer to Figure 1 for details.
Serum Concentration of Blood Sugar and Lipid Profile Parameters
Our results revealed that 278 (55.6%) of the participants had severely elevated HbA1c levels (=10%), which was considered highly significant (p<0.05) compared to normal values. Additionally, approximately half of the participants had moderate elevation (250-299 mg/dl) in random blood sugar levels. The lipid profile of the participants showed significant elevation in these parameters compared to normal values. Specifically, there was mild elevation in cholesterol levels for 184 participants (36.8%) and TG levels for 387 participants (77.4%).
Relationship between Gender and Age with Serum Cholesterol Elevation
We found that 184 (36.8%) of the participants had a highly significant (p<0.05) mild elevation in serum cholesterol levels when compared to other types of elevations.
Out of the total participants, 98 (42.6%) were male, with 36 (15.7%) of them being within the age range of 50 years or older. Additionally, 86 (31.9%) participants were female, with 31 (11.5%) of them falling within the age range of 40-49 years old. Refer to Figure 2 for more details. On the other hand, out of the total participants, 33 (46.5%) were single, with 17 (23.9%) of them being within the age range of 20-29 years old. Furthermore, among the married participants (151, or 35.5% of the total), most of them (53, or 12.5% of the married) were within the age range of 50 years or older. The association between marital status and age was found to be highly significant (p<0.05) when compared to the single status. Refer to Figure 2 for visual representation.
Relationship between HbA1c and Serum Cholesterol Elevation
We observed that 278 (55.6%) of the participants had severe elevation in HbA1c levels, of which 83 (29.9%) had mild elevation, 16 (5.8%) had moderate elevation, and 73 (26.3%) had severe elevation in serum cholesterol. Interestingly, all of these participants were within the age range of 40-50 years old. Additionally, 79 (15.8%) participants had mild elevation in HbA1c, while 62 (12.4%) had moderate elevation. Both of these groups were associated with mild elevation of serum cholesterol and were within the same age range of 40-50 years old. For more detailed information, refer to Figure 3.
The study’s findings suggest a direct relationship between elevated lipid profiles and elevated HbA1c levels, which indirectly indicates the risk of both macro- and microvascular complications. HbA1c levels could serve as a potential biomarker for identifying T2DM patients at risk for cardiovascular disease (CVD) and guiding patient care [10]. Our results demonstrate a significant positive correlation between cholesterol levels and HbA1c. While one study found no association between HbA1c and cholesterol, several other studies [11, 12] reported a positive correlation between high HbA1c levels and cholesterol, consistent with the findings of our study [13].
In our investigation, participants with HbA1c levels above 10% (indicative of poor glycemic control) exhibited significantly higher blood cholesterol levels, particularly within the age range of over 40 years. This elevation in cholesterol may be due to dietary habits or patient management strategies as prescribed by physicians. However, we did not observe significant differences in moderate and mild elevation of HbA1c. Another study also found that individuals with HbA1c levels over 10% had higher TC, LDL-C, and cholesterol levels than those with HbA1c values under 10%. It appears that patients with better glycemic control experience less dyslipidemia compared to those with poor glycemic control [14, 15].
Our study’s findings, as shown in Figure 2, demonstrate a high prevalence of hypercholesterolemia associated with gender. Of the males, 36 were within the age range of = 50 years old, while out of the females, 31 were within the age range of 40-49 years old. Furthermore, among the participants, 33 (46.5%) were single, with 17 (23.9%) of them within the age range of 20-29 years. In contrast, among the married participants (151, 35.5% of the total), most (53, 12.5% of the married) were within the age range of = 50. These factors are well-known risk factors for CVD, and disturbances in cholesterol metabolism could contribute to heart attacks. Dyslipidemia in females may be attributed to sex hormone effects on body fat distribution, leading to altered lipoprotein levels [16]. Other factors such as coagulation variations, obesity patterns, and the role of hyperinsulinemia may also contribute to dyslipidemia [17]. Hyperinsulinemia regulates the activity of enzymes like cholesterol ester transport protein and lipoprotein lipase, all of which can contribute to dyslipidemia in diabetes patients [17].
The authors extend their gratitude to Al-Zahrawi University College for providing excellent research facilities.
The authors declare no conflict of interest.