Prevalence, patterns and associated risk factors for dyslipidaemia among individuals attending the diabetes clinic at a tertiary hospital in Central Malawi

Background Dyslipidaemia among individuals with diabetes is a significant modifiable risk factor for atherosclerotic cardiovascular diseases (ASCVDs). ASCVDs are a major cause of mortality and morbidity globally, especially in people with diabetes. In Malawi, limited data exist on the prevalence and biochemical characteristics of diabetic dyslipidaemia. This study investigated the prevalence and biochemical characteristics of dyslipidaemia in individuals attending the diabetes clinic at Kamuzu Central Hospital, the largest tertiary referral hospital in Central Malawi. Methods Using a cross-sectional design, sociodemographic, medical and anthropometric data were collected from 391 adult participants who were enrolled in the study. Blood samples were analysed for glycosylated haemoglobin (HBA1c) and fasting lipid profiles. The prevalence of dyslipidaemia was calculated, and the biochemical characteristics of the dyslipidaemia were defined. The associations between dyslipidaemia and risk factors such as sociodemographic characteristics, obesity, and HBA1c levels were evaluated using logistic regression analysis. Results Prevalence of dyslipidaemia was observed in 71% of the participants, and elevated low-density lipoprotein cholesterol was the most frequent lipid abnormality among the study participants. On bivariate analysis, dyslipidemia was positively associated with female sex [OR 1.65 (95% CI 1.05–2.58); p = 0.09], age ≥ 30 years [OR 3.60 (95% CI 1.17–7.68); p = 0.001] and overweight and obesity [OR 2.11 (95% CI 1.33–3.34); p = 0.002]. On multivariate analysis, being overweight or obese was an independent predictor of dyslipidaemia [AOR 1.8 ;( 95% CI 1.15–3.37); p = 0.04]. Conclusion Dyslipidaemia was highly prevalent among individuals with diabetes in this study, and elevated low-density lipoprotein cholesterol was the most frequent lipid abnormality. Overweight and obesity were also highly prevalent and positively predicted dyslipidaemia. This study highlights the importance of appropriately addressing dyslipidaemia, overweight and obesity among individuals with diabetes in Malawi and other similar settings in Africa as one of the significant ways of reducing the risk of ASCVDs among this population.

Approximately 537 million adults are living with diabetes mellitus (DM) globally, 75% of which live in low and middle-income countries (LMICs) (1).In Malawi, the prevalence of DM is estimated at 7% (2).DM is a signi cant risk for atherosclerotic cardiovascular diseases (ASCVDs), such as stroke, which is the major cause of morbidity and mortality in people living with DM (3).ASCVDs cause 31% of all global deaths, with 80% occurring in LMIC (4).Dyslipidaemia complicates DM and doubles the risk of cardiovascular events in individuals with DM (3,5).Dyslipidaemia is a driver of atherosclerosis and is an indirect cause of at least 2 million annual deaths and nearly 30 million disabilities globally (4).
Dyslipidaemia denotes a group of lipid abnormalities characterised by one or more of the following: elevated total cholesterol (TC), elevated low-density lipoprotein cholesterol (LDL-C), decreased highdensity lipoprotein cholesterol (HDL-C), and elevated triglycerides (TG) (4,6).Diabetic dyslipidaemia is typically characterised by elevated triglycerides (TG), decreased high-density lipoprotein cholesterol (HDL-C) with normal to mildly elevated low-density lipoprotein cholesterol (LDL-C), owing to the overproduction of TG-rich very-low-density lipoprotein (VLDL) particles in the liver and increased exchange of TG in VLDL for cholesteryl esters in HDL and LDL-producing sdLDL (7)(8)(9).
There is limited data on the prevalence, biochemical characteristics, and risk factors of dyslipidaemia among individuals with DM in Malawi.This cross-sectional study aimed to determine the prevalence of dyslipidaemia, biochemical characteristics, and the associated risk factors among individuals with DM attending the adult DM clinic at Kamuzu Central Hospital (KCH), the largest tertiary referral hospital in Central Malawi.

Study design and setting
This quantitative cross-sectional study was conducted at the adult KCH, the largest tertiary referral hospital in Lilongwe, in central Malawi.KCH serves a population of about 7 million people in Central Malawi.The study population was adults aged 18 years and above with DM, either type 1 (T1DM) or type 2 (T2DM), irrespective of HIV status and attending the KCH DM clinic.Data were collected between March and June 2021.

Inclusion and exclusion criteria
Participants were included in the study if they were con rmed DM patients aged 18 years and older and consented to participate.We excluded pregnant participants, those with an incomplete medical history, those with fever or history of an active infection, and those from whom blood sample collection was unsuccessful.

Study population and sampling strategy
Study participants were enrolled when they visited the DM clinic.The study period coincided with the Coronavirus disease 2019 (COVID-19) pandemic and there were limited booked patients for the clinics.In that case, consecutive sampling was used to recruit participants in the study until the sample size was reached.
The clinical research nurse collected and documented data using an interviewer-administered questionnaire.Sociodemographic data were collected and recorded.Weight and height measurements were performed and recorded, from which the body mass index (BMI) was calculated.Clinical nurses also collected two blood samples in ethylenediaminetetraacetic acid (EDTA) tube for HBA1c tests and another in a plain tube for fasting serum lipid pro le testing for LDL-C, TG, TC and HDL using an automated Erba XL640 (USA) by a quali ed laboratory technologist.

De nition of Parameters
Dyslipidaemia was de ned as the presence of one or more lipid abnormalities among the study participants: TC > 200mg/dl, LDL-C > 100mg/dl, TG > 150 mg/dl and HDL-C < 40 mg/dl (10,11).Dyslipidaemia was further classi ed as isolated when a single abnormal lipid parameter (TC, TG, HDL-C or LDL-C) was present; combined when two lipid parameters (elevated TG, low HDL-C or elevated LDL-C) were detected; and mixed when all three lipid parameters are abnormal (elevated TG, low HDL-C and elevated LDL-C) (3).Poor glycaemic control was de ned as HBA1c of > 7% (10).BMI categories were classi ed according to the WHO classi cation as underweight if BMI < 18.5, normal if BMI was between 18.5 and 25, overweight if BMI was between ≥ 25.0 and 30, and obese if BMI ≥ 30.0 (12).

Statistical analysis
Data were entered Microsoft Excel spreadsheet and statistical analysis was performed using STATA 17 (StataCorp LLC).The Shapiro-Wilks normality test was used to test the data for normality.Descriptive statistics for continuous data were expressed as the means or medians, and proportions for categorical data.The Chi-squared or Fisher's exact test for independent variables was used to compare categorical data.The t-test was used to analyse the differences in mean difference in lipid concentrations between any two groups.Bivariate logistic regression was used to evaluate risk factors for dyslipidaemia, such as age groups, DM type, sex, or BMI categories.Multivariate logistic regression analysis accounted for confounding and included all variables with a p < 0.1 on bivariate analysis.In all cases, a p-value < 0.05 was considered signi cant.

Results
Participants Recruitment Process A total of 401 participants were screened for inclusion in the study, and 391 were enrolled (Figure 1).Participants were excluded from the study because they left before conducting clinical assessments or blood sample collection was not performed before blood pressure measurement (Figure 1).

Participant's sociodemographic and clinical characteristics
Most of the study participants were females (64%), middle-aged with a mean age of 52 ( 13) years (Table 1).The HIV prevalence in the population was 11%, but the status was unknown in 13% of the participants.The mean blood pressure readings were 142 (26) mmHg systolic and 87.50 (15) mmHg diastolic.The mean HbA1c level was 10.29 (3.35).Table 1.Participants' baseline characteristics.The prevalence of overweight and obesity in the study was 70% (30% overweight and 40% obese, respectively).Figure 2 shows the BMI categories classi ed by sex.Female participants were more likely to be overweight and obese than the male participants [OR 5.32 (95% CI, 3.34 -8.47); p<0.001].

Variable
Prevalence of dyslipidaemia and the biochemical patterns in the study population Dyslipidaemia was observed in 71% of the study participants (Figure 3).Notably, elevated LDL-C concentrations were the most frequent lipid abnormality observed in 55% of the participants, and the least frequent type of lipid abnormality was decreased levels of HDL-C.
Table 3 summarises the dyslipidaemia patterns regarding single, combined and mixed dyslipidaemia among participants who had dyslipidaemia, respectively.Isolated dyslipidaemia was the most common form, seconded by combined dyslipidaemia, and mixed dyslipidaemia was the least common pattern.In all the dyslipidaemia categories, elevated LDL-C was highly prevalent.

Discussion
This study at the largest tertiary referral hospital in central Malawi reports a high rate of dyslipidemia among adult individuals with diabetes, with elevated LDL-C as the most common lipid abnormality.Dyslipidaemia was positively associated with overweight and obesity, female sex, and age above 30 years.Overweight and obesity emerged as an independent predictor for dyslipidaemia among the study participants.
The study's high prevalence of dyslipidaemia is comparable to other studies among individuals with DM in other Sub-Saharan African countries (3,10,13).These results are consistent with the previously reported high prevalence of dyslipidaemia at another public tertiary referral hospital in Malawi among individuals with DM and hypertension (14).Dyslipidaemia is a signi cant modi able determinant of ASCD globally and in Africa (5,15) and requires proactive screening and management, especially among individuals at high risk, such as those living with DM.Sadly, there is a lack of aggressive efforts towards addressing dyslipidaemia among individuals with DM (14).Plausibly, the poor screening and management of dyslipidaemia contribute to the escalating rates of ASCDs in such LMICs (16).
Elevated LDL-C was the most common lipid abnormality in the present study.Elevated LDL-C-C drives atherosclerosis and is the target for treating dyslipidaemia (17,18).Therefore, the study participants were at higher risk for ASCDs, given the elevated levels of LDL-C, and should be treated with lipid-lowering therapy (18).Ideally, all patients with DM aged between 40 and 75 years, regardless of the presence of complications, are recommended to be on statins for the primary prevention of ASCDs to achieve an LDL-C target of < 70mg/dl (18,19).More than 80% of the study participants were between 40 and 75 years old and ideally required at least moderate-intensity statin therapy (18,19).In the present study, we did not investigate the proportion of participants who were on lipid-lowering pharmacotherapy, as it was beyond the scope of this study.However, dyslipidaemia treatment rates among people with DM were reported at 0% at another public tertiary hospital in Malawi (14).Factors such as frequent stock-outs of lipogram reagents, unavailability of local guidelines for the management of dyslipidaemia and inexperience healthcare personnel hinder the efforts towards addressing dyslipidaemia among people with DM in Malawi and other LMICs (14,20,21).It is imperative, therefore, that the Ministry of Health in Malawi and its partners reinforce efforts toward strategies for optimally addressing dyslipidaemia among patients with DM to reduce the risk of ASCDs.
Overweight and obesity were highly prevalent (70%) in this study and independently predicted dyslipidaemia.The rates of overweight and obesity among the participants were higher than the 40% rate reported in the general population in urban Malawi (22).The difference may be because the present study involved participants with DM, of whom 81% had T2DM, for which overweight and obesity are known risk factors (23).However, given the study's cross-sectional nature, it was complex to establish the temporal relationship between DM, overweight and obesity and dyslipidaemia.Similar to our results, other African studies have reported overweight and obesity as independent predictors of dyslipidaemia (4,6,13).Socio-economic transitions such as urbanisation in uence sedentary lifestyles and poor dietary habits, promoting overweight and obesity in Africa and Malawi (22,24).Recent data suggest that more than twothirds of the Malawi adult population do not consume recommended adequate amounts daily of fruits and vegetables (25).Adequate consumption of whole fruits and vegetables is essential for better BMI control and normal nutrition (26), and should be encouraged, especially among people with DM (26).
Females in this study were more likely to be overweight and obese than men, as reported in Malawi (22) and other African countries (23).Overweight and obesity in women in Malawi, like in many African countries, are in uenced by the socio-cultural context where it is revered and regarded as a sign of high economic standing, beauty and a sign of fertility (23,27,28).Additionally, in urban settings, women are engaged mainly in jobs requiring less physical activity.In Lilongwe city, the risk of obesity is expectedly high (27,29).Overweight and obesity must be addressed among individuals with DM to curb dyslipidaemia and the risk of ASCDs in this population (9).Malawi has in-country-trained dieticians working at tertiary-level healthcare facilities and should reinforce lifestyle modi cations, including proactive physical activity and appropriate cardiovascular-friendly dietary habits, towards reducing the rates of overweight and obesity among individuals with DM (30,31).
Poor glycaemic control, as indicated by HBA1c ≥ 7%, was observed in 85% of participants in the present study.These results are similar to previous studies in Southern Africa (10).If left unmanaged, poor glycaemic control positively in uences dyslipidaemia (32) and increases the risk of cardiovascular events for every 1% increase in HBA1c level (33).These considerations necessitate re-strategising the monitoring and delivery of e cacious interventions like dietary adjustments, glucose monitoring and physical exercising to help improve glucose control.
Although smoking and alcohol consumption are known risk factors for dyslipidaemia, there was no statistically signi cant association with dyslipidaemia in this study.The prevalence of smoking and alcohol consumption in this study was lower than NCD STEPwise survey ndings (1% and 5% versus 11.2% and 17%, respectively) (25).The lack of signi cant association would have likely been due to the lack of statistical power, owing to the low prevalence of the conditions in this study.Moreover, the participants may have underreported since they are advised to abstain from alcohol and smoking at the DM clinic during health education sessions.
The HIV prevalence in the study population was 11%.A previous study in Malawi showed that the rates may be as high as 20% among people with DM (14).Dyslipidaemia and DM increase the risk of ASCDs up to 2.4-fold in people living with HIV (PLWH) (19,(34)(35)(36)(37).In this study, the association of HIV and dyslipidaemia approached signi cance, and low power may have in uenced the lack of statistical signi cance due to the low prevalence of HIV among the participants.Nevertheless, it is essential to carefully consider the choice of lipid-lowering therapy in PLWH with DM and dyslipidaemia (38).
Atorvastatin is the preferred choice of statin among PLWH, unlike simvastatin and rosuvastatin, due to the high risk of drug interactions with antiretroviral drugs (38, 39).Clinicians must evaluate potential drug-drug interactions between lipid-lowering agents and ARVs before prescription (38,40).
This study had its limitations.The cross-sectional nature precluded any temporal association between the risk factors and dyslipidaemia.In addition, the molecular and humoral mechanisms, such as the in uence of adiponectin in the pathophysiology of obesity and dyslipidaemia, were not evaluated, as these were beyond the scope of this study (41,42).Whilst the study complements previous ndings on diabetic dyslipidaemia in Malawi at tertiary hospitals, the results may not be generalizable to the rural settings of Malawi.Studies from rural settings would help inform country-wide clinical guidelines on screening and management of diabetic dyslipidaemia in Malawi.

Conclusion
This study highlights the high prevalence of dyslipidaemia characterised by a high frequency of elevated LDL-C, with overweight and obesity as an independent positive predictor.
Risk factors associated with dyslipidaemia among the study participants.Dyslipidaemia was positively associated with female sex, overweight and obesity (Table3).T2DM was not statistically signi cantly associated with dyslipidaemia.Smoking status, alcohol consumption, education, occupation and HBA1c greater than 7% showed no signi cant association with dyslipidaemia in this study population.

Table 3 .
Associated risk factors for dyslipidaemia in the study participants.
Malawi and other LMICs as one of the signi cant ways of reducing the risk of ASCDs among individuals with DM.Lifestyle modi cations such as better dietary habits, physical activity and pharmacotherapy should be reinforced for primary and secondary prevention of cardiovascular events.Data in rural settings of Malawi are required to provide generalised data on the magnitude of dyslipidaemia in patients with DM in Malawi.Additionally, the availability and impact of statin use in public hospitals in Malawian patients with DM warrant further research attention.
The results underscore the importance of appropriately addressing dyslipidaemia, overweight and obesity among individuals with DM in