Cardiovascular disease risk factors in a Nigerian population with impaired fasting blood glucose level and diabetes mellitus

Impaired fasting glucose (IFG) is a hyperglycaemic condition that predisposes individuals to high risk of developing type II diabetes (T2D) and cardiovascular disease (CVD) [1]. It is characterised by insulin resistance, beta cell dysfunction, increased lipolysis, inflammation, sub-optimal incretin effect and hepatic glucose overproduction [2]. There have been debates on whether IFG, a component of prediabetes, should be considered in the same manner with T2D since in both conditions there is hyperglycaemic-induced toxicity [3, 4]. It is noted that progression from IFG to T2D can occur due to worsening oxidative stress [3], insulin resistance or beta cell dysfunction [4], and in the long term predisposes to increased risk of CVD. This is where routine screening can be beneficial in aiding early identification and application of management practices, since the process of progression is not abrupt.

In Africa, more than two thirds of people with diabetes are undiagnosed [5], giving room for complete transition of the early stages of impaired glucose regulation to overt disease condition. About 14.2 and 34.9 million adults of age 20 – 79 years have diabetes and prediabetes with estimated prevalence of 3.2% (2.1 – 6.7%) and 7.9% (4.8 – 21.9%), respectively. However, the most glaring part is the indication that the prevalence of prediabetes will double by the year 2040 and this is more than that projected for T2D [5]. Based on the 2013 Global Burden of Disease study [6], about 90.5% of stroke burden was attributable to lifestyle-related risk factors, cluster of metabolic risk factors (high blood pressure, IFG, elevated total cholesterol and low glomerular infiltration) and environmental factors. Lifestyle-related risk factors and metabolic risk factors contributed to 74.2% and 72.4% stoke burden, respectively and the population attributable fraction of risk factors in low-middle-income countries increased from 1990 to 2013 [6]. Such observations therefore call for periodic screening, monitoring and appraisal of data on risk factors for metabolic diseases.

CVD risk screening in Nigeria is sub-optimal, even though evidence indicates early onset of disease burden [7, 8], which in part contributes to the low life expectancy and quality of life of Nigerians [9]. One of the effective approaches to early identification of CVD risk is the utilisation of risk assessment models and these have been shown to be better than clinical judgement [10]. Although the assessment of co-occurrence of risk factors for CVD is largely studied in diabetic patients [11‐14], the extent that these trends affect the seemingly healthy populations with IFG in Nigeria needs to be documented.

The use of risk assessment models, which provide the bedrock for early identification of diabetes and consequential CVD within a resource constraint population are unclear within African population [15]. Therefore, this study seeks to characterise CVD risk factors in subjects with impaired fasting glucose (IFG) and diabetes by specifically predicting the age of IFG and diabetes co-morbidity with CVD risk factors and to classify the risk factors in IFG in a large apparently healthy Nigerian population.

This study shows that there is higher prevalence of IFG than undiagnosed diabetes among the study Nigerian population. Further, co-morbidity of modifiable risk factors for chronic diabetes and CVD, such as dyslipidaemia and HBP, were more predominant in IFG than diabetes subjects. Several studies report that the transition to westernised ways of life, which may lead to unhealthy eating and physical inactivity, is possibly responsible for this increase in multi-morbidity [33‐35]. It has been shown that the relative risk of coronary heart disease in individuals with 1, 2 or >3 CVD risk factors is up to 2, 4 and 7-folds, respectively [14]. More so, the fact that the hyperglycaemic condition of IFG worsens the already frail state of endothelial dysfunction and insulin resistance [4], prompts for action on community-wide implementation of diabetes and CVD risk factor identification and prevention.

Age distribution of IFG and co-morbidity of IFG with CVD risk factors showed upward trend from the lowest age group, plateauing at 40 – 49 years. This finding agrees with other studies on independent CVD risk factors, which showed an increase in prevalence with increase in age [36, 37]. No significant predicted age difference was observed in population with and without IFG and IFG co-morbidity with risk factors, except in overweight/obese. In other words, IFG or its co-morbid risk condition do not have age preference unlike in diabetes where the age difference was found to be statistically significant (p < 0.018) between age of occurrence (Table 4). However, the fact that co-existence of other risk factors with impaired glucose regulation increases the risk of chronic diabetes and CVD [38], underscores the need for frequent risk assessment for prediabetes in this population. Establishment of opportunistic screening strategies using already available communicable disease screening centres would be a cost-efficient approach.

Our findings also showed that predicted age of IFG, diabetes and their co-occurrence with other risk factors were within same range (40 – 45 years). Evidence shows that risk assessment models for CVD have diabetes as dichotomous (Yes or No) and considers subjects from 40 years of age. It is argued that the problem of such dichotomy is that hyperglycaemia in impaired fasting glucose or impaired glucose tolerance is missed via a NO answer, when assessment and treatment of CVD risk in prediabetes should be as in diabetes [39, 40]. The implication is that information pertaining to the primordial forms of glucose dysregulation are not brought to fore in Nigeria to aid early identification of the ‘at risk’ population, since risk of an individual is usually not assessed until overt diabetes that surfaces with huge symptoms. This emphasises that intervention based on outcome of utilisation of available risk assessment tools would not identify a substantial proportion of the population at increased risk of CVD, given the proportion of IFG individuals with co-morbid risk factors.

Furthermore, our findings delineated high level of blood total cholesterol as the most important risk factor predominant in population with IFG. Some studies in Nigeria identified high prevalence of risk factors [41‐43], and insight into the order of importance and occurrence would assist in screening and treatment of the at-risk individuals. However, based on chain of events as shown in Figs. 1 and 2, it may seem important to integrate screening for hypertriglyceridaemia in risk assessment models for prediabetes conditions in the Nigerian population, as it strongly contributes to the co-morbidity in IFG-normocholesterolaemic-overweight/obese-nonhypertensive individuals. This implies that in the absence of HBP, there is increased chance of dyslipidaemia (high total cholesterol and/or triglyceride levels) and overweight/obese among the sample population with IFG. Furthermore, hypertriglyceridaemia was found to have higher independent predictive ability in classifying IFG than age. It was opined to be an essential risk factor contributing to discordance of results from the use of the ATPIII/Framingham risk score and metabolic syndrome in screening individuals at 10-year risk of CVD [44].

The increasing identification of IFG and undiagnosed diabetes is an issue for concern, requiring concerted and pragmatic approach. It is important to emphasise the need for screening of IFG at least, based on the evidence of high co-morbid CVD risk factors associated with it. The feasibility of screening by measuring FBG levels leads to increased chances of early identification when targeted at patients with multiple risk factors [45]. The epidemiological evidence that the majority of cases of diabetes/CVD are undiagnosed in this part of the world is an indication that assessment and management of CVD risk based on screening for diabetes in subjects with high blood pressure [46] may miss out early identification of other risk factors that co-exist in individuals without evidence of hypertension. This is on the premise that the etiological mechanisms of clustering of the CVD risk factors are not well understood. However, one of the factors undermining risk screening of dyslipidaemia in Nigeria is the high cost [20, 47], and although obesity screening is affordable, there is no evidence regarding its assessment against mortality outcome other than metabolic outcome, and in most cases the proportion of metabolically healthy obese phenotype is not accounted for in studies reporting high prevalence of obesity. Therefore, future studies exploring association of these phenotypes with prediabetes and other risk factors are required to elucidate the order of magnitude of IFG/IGT co/multi-morbidity with CVD risk factors in sub-Sahara Africa.

The higher prevalence of co-morbidity of CVD risk factors with IFG than in diabetes mellitus shows that targeting only the older adult individuals presenting at health institutions for risk factors identification and intervention would not abate the increasing incidence of diabetes and CVD in Africa. There is need for appropriate risk assessment models for prediabetes considering that IFG and its co-morbid risk factors are relative prevalent in young adults and probably more in middle-aged adults.