Risk Factors and Diabetes Related Complications Frequency in the Population of the Northeastern Morocco

Objectives: Diabetes is one of the most challenging health problems in the 21 century that brings a considerable economic burden on worldwide healthcare resources. Indeed, people with diabetes have a higher lifetime healthcare expenditure due to the long-term complications, which include micro and macrovascular complications. This study sought to estimate the frequency of diabetes complications, and to investigate the associated risk factors. Methodology: Data were obtained from the medical records of 2401 diabetic patients followed at the Reference Center of Diabetes and Chronic Diseases (RCD) in Oujda (Morocco) during the period 2006-2011. Results: Our sample of 2401 diabetic patients include 64.7% women. 32% of patients have one or more complications; retinopathy is the most frequent complication (16.8%), followed by nephropathy (12.4%), cardiovascular diseases (5.4%), neuropathy (3.6%) and diabetes foot (2%). Logistic regression in univariate followed by multivariate analysis has showed that age, duration of diabetes and high albuminuria are the major risk factors for the development of diabetic complications in both type 1 and type 2 diabetes. Conclusions: Nearly one third of diabetic patients were affected by at least one diabetic complication; retinopathy is the most common complication in these patients. Strengthening programs to improve diabetes management and to reduce the risk of these complications should be a high priority in order to control the cost of treatment.


Introduction
Diabetes is a global threat to human and economic development [1] [2] and one of the most frequent chronic metabolic disorders that continues to present a large worldwide health issue in all countries.It is a disease related to a malfunctioning biological mechanism of blood glucose regulation.When we eat, the blood sugar level increases, the carbohydrates are then converted to glucose.The pancreas detects the increase in blood sugar and the beta cells secrete insulin that allows glucose to enter the cells of the body: in the muscles, in the adipose tissue and in the liver where it will be able to be transformed and stored.The glucose then decreases in the blood.In case of diabetes, this regulation system does not work; the pancreas do not produce enough insulin or cannot use insulin properly, or both.In diabetes, glucose in the blood cannot move efficiently enter into cells, so blood glucose levels remain high [3].There are four categories of diabetes: type 1 diabetes (occurs when the beta cells of the pancreas are unable to produce insulin); type 2 diabetes (accounts for ~90% of cases of diabetes: occurs when the beta cells do not produce enough insulin or when the body is resistant to insulin actions); gestational diabetes (diabetes occurring during pregnancy) and finally the group of other types of rare specific cases of diabetes (specific genetically defined forms of diabetes or diabetes associated with other diseases or drug use) [4].The Diabetes type 1 (DT1) formerly called insulin-dependent diabetes (IDD) or juvenile-onset diabetes, appears during childhood or adolescence (most < 25 years and before the age of 6 months) [4] [5] while, the diabetes type 2 (TD2) previously referred to as non-insulin-dependent diabetes (NIDD), or adult-onset diabetes, usually occurs in people over > 25 years, and its incidence increasing with the increasing rate of obesity in children and adolescents [4] [5].
The diabetes symptoms are the same regardless of its type (frequent urination, extreme thirst, excessive hunger, tiredness, and weight loss).Urbanization, increased consumption of saturated fats and sugar, and a more sedentary lifestyle are increasing the prevalence of diabetes in many countries around the world [6].According to the IDF Diabetes Atlas, in 2017, there were 451 million (8.4%) (age 18 -99 years) people with diabetes worldwide [7].The global prevalence of this silent killer is estimated to increase to 693 million (9.9%) by 2045 [7].
Several differences were found in diabetes prevalence by age group, gender, World Bank income group and geographical region.In high-income countries, diabetes prevalence reached (22%) in the 75 -79 age group and in middle-income countries among the 60 -74 age groups (19%).In low-income countries, the prevalence of diabetes was (8%) among the 55 -64 age group.The prevalence of diabetes among 65 -69 year olds was 3 times higher in highincome countries compared to low income countries [7].In 2017, the prevalence of diabetes among women (8.4%) (18 -99 years) was lower than in men (8.9%) [7].The highest diabetes prevalence in the world was found in the North American and Caribbean Region (10.8%) followed by the Midlle East and North DOI: 10.4236/ojepi.2018.83014Africa (10.5%), the South-East Asia (9.6%), the Western Pacific (8.5%), and the South and Central America (7.5%) while, the lowest was in the Africa Region (4.2%) [8].The increasing prevalence of diabetes has a great impact in terms of economic burden worldwide.The Current estimates of global healthcare expenditures due to diabetes for people aged 20 -79 years are 727 billion and are expected to increase to USD 850 billion when expanding the age group to 18 -99 years [7].
Socio-economic status, demographic factors and ethnicity are important determinants of diabetes.In fact, higher diabetes proportions were seen in the people who have highest income quintile, in those educated up to advanced levels, and in the urban sectors [9].Moreover, the risk of developing diabetes increases with family history, age, obesity, hypertension and lack of physical activity [10] [11] [12].
Vascular impairment during diabetes affects the entire vascular network of the body, whatever the size of vessels and tissues which they irrigate.We classically distinguish microangiopathic (kidney, eye, nerve) and macroangiopathic complications, which consist of cardiovascular, cerebrovascular and peripheral vascular diseases.The excess of glucose available (due to diabetes) enters abundantly into the cells of the vascular wall especially endothelial, smooth muscle cells, pericytes and related cells, whose glucose uptake, dependent on the GLUT1 transporter, is not regulated by the insulin.The flow in the pathway of glycolysis is very increased [13]  Moreover, this flow in the pathway of glycolysis leads to mitochondria, whose protection systems in the electron transfer (antioxidant mechanisms) are flooded and insufficient.Reactive oxygen species (ROS) are generated and will randomly react with this or that molecule, modifying it permanently: it is the oxidative stress related to hyperglycemia.The cell will be modified, and does not properly perform its function (endothelial dysfunction, for example).The subsequent consequences depend on the vessel and the tissue involved.The early pathological events are very similar within small and large vessels, suggesting that changes within the microcirculation can lead to the development and progression of large vessel disease [16].It is well known that vascular complications in a given tissue are often accompanied by signs of pathology in other vascular territories [17].The strong association between diabetic nephropathy (DN) and diabetic retinopathy (DR) is perhaps the example that is best known to clinicians [16]; The association of DR and DN with cardiovascular disease is another evidence of the intersection of microvascular and macrovascular complications associated with diabetes [16] [17].
In North Africa, the prevalence of chronic diabetes complications ranges from 8.1% to 41.5% for retinopathy, 21% -22% for high albuminuria, 6.7% to 46.3% DOI: 10.4236/ojepi.2018.83014for nephropathy and 21.9% to 60% for neuropathy [18].Many complications of diabetes can be prevented or delayed by preventive measures and management programs of this disease, especially by identification of risk factors, early diagnosing of diabetes, and educating patients and health professionals.
In Morocco, a North African country which has been undergoing a demographic, nutritional and epidemiological transition during the last two decades [19] [20], the prevalence of diabetes is increasing rapidly.According to the national investigation conducted in 2000 on a Moroccan representative sample aged 20 and over showed that the prevalence of diabetes was 6.6% and type 2 diabetes (T2D) was found to constitute 90% of all cases of diabetes [21].Furthermore, the number of adults with diabetes in Morocco is predicted to rise from 1.5 million in 2010 to 2.5 million by 2030 [22].In Eastern Morocco, diabetes and its complications are major public health problems.The study of our research team revealed a prevalence of 10.2% for diabetes in this region for adults aged 40 and older [23].To the best of our knowledge, there are no studies that have focused on diabetes complications and its risk factors in Eastern Morocco.

Objectives
This study aims to estimate the frequency of diabetic complications, and to investigate the association between sociodemographic and clinical risk factors and the occurrence of the diabetes-related complications.

Study Population
This is an epidemiological study that was conducted at the Reference Center for Diabetology and Chronic Diseases "RCD".
Its main aim is the management of diabetes complications and the reduction of its mortality among diabetic patients.
This study focuses on a sample of 2401 diabetic patients who visited the "RCD" during the period of 2006-2011.Inclusion criteria were: having type 1 (T1D) and type 2 diabetes (T2D), and having regular medical monitoring (patients who have a follow-up of 2 years and who have received at least one consultation per year).Exclusion criteria included gestational diabetes and irregular medical monitoring (patients who are enrolled in the center but who rarely come for consultations).

Sample Size
The number of patients who participated in the study was 2401.This number was calculated using the following formula: n = z² × p (1 -p)/m 2 n = sample size; z = confidence level according to the standard normal distribution (for a 95% confidence level, z = 1.96); p = estimated proportion of the population with complications (50%); m = tolerated margin of error (2%).n = (1.96)²× (0.5)(1 − 0.5)/(0.02)²= 2401 Our sample of 2401 diabetic patients was selected (by random sampling) from a total population of 11,757 diabetic patients followed at the "RCD" during the period 2006-2011 using inclusion and exclusion criteria.

Data Collection
The following variables were collected from the medical records of patients: age, gender, educational level, occupation, socio-economic status, medical insurance, type of diabetes, diabetes duration, diabetes treatment, alcohol consumption, smoking status, glycated hemoglobin (HbA1c), hypertension, body weight, height, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), albuminuria, complications including cardiovascular diseases, diabetic foot complications, nephropathy, neuropathy, retinopathy, and data related to family history of diabetes.
• Based on the recommendations of the National Cholesterol Education Program Adult Treatment [29], the following were considered as acceptable target values: total cholesterol (TC ≤ 200 mg/dl), low density lipoprotein cholesterol (LDL-C ≤ 130 mg/dl), triglycerides (TG ≤ 150 mg/dl), and high density lipoprotein cholesterol (HDL-C ≥ 40 mg/dl).

Statistical Analysis
In this study, quantitative variables were expressed as mean ± standard deviation and qualitative variables were expressed as frequency or percentage.

Results
The socio-demographic and bio-clinical data of 2401 diabetic patients are shown in (Table 1).64.7% of the total sample were women.The sex ratio (men/women) was 0. In the present study, we found the overall frequency of diabetes complications to be 32%.The most common complication was retinopathy (16.8%), followed by nephropathy (12.8%), cardiovascular diseases (5.4%), neuropathy (3.6%) and diabetic foot complications (2%) (Figure 1).
Of them, 58 (32.8%) were females and 50 (40.7%)were males with no significant difference between them (NS) (Table 2).Moreover, the analysis of the data DOI: 10.4236/ojepi.2018.83014 proved that the risk of developing complications increased with advancement in age (Table 2).
A majority of the subjects with complications were illiterate (42.1%) and had a diabetes duration > 20 years (60.7%)(Table 2).Thus, the results showed a highly significant difference (P < 0.001) between patients with complications and those without for several parameters: hypertension, overweight and obesity, creatinine and albuminuria but no significant difference was found between them about other parameters: cholesterol and triglycerides (Table 2).
Using simple logistic regression analysis, age, educational level, diabetes duration, overweight and obesity, hypertension and a high level of albuminuria were significantly associated with the occurence of diabetes complications (Table 3).

Complications in Type 2 Diabetes
Table 5 shows the distribution of diabetes complications by socio-demographic and bio-clinical settings among type 2 diabetics.In the whole population 419 (30.5%) of women had complications versus 241 (33.2%) of men; there was no gender difference in diabetes complications frequency (NS).However, older people (≥65 years) showed a higher frequency (42.1%) of diabetes complications.
Besides, diabetics who had hypertension, poor glycemic control and a high albuminuria had a higher frequency of complications (40%, 33.1% and 38.8% respectively).
As illustrated in Table 3, age, diabetes duration, hypertension, poor glycemic control (HbA1c > 7%) and a high level of albuminuria were all significantly related to the development of complications and the maximum risk was with hypertension (OR = 2.05; CI: 1.70 -2.47, P < 0.001) in univariate logistic regression analysis.A multivariate logistic regression analysis was then realized to identify which of the latter were related to diabetes complications.The results listed in Table 4 show that age of the patient, diabetes duration, hypertension and a high albuminuria level were the risk factors of diabetes complications in T2D in this study.

Discussion
This study, the first of its kind in Eastern Morocco, describes the socio-demographic, clinical features and complications of 2401 diabetic patients, and provides important data on the frequency of diabetes complications and the associated risk factors.These data will serve as references for later studies and help to develop effective strategies against the development of diabetes complications, in order to reduce the mortality rate caused by this endocrine disorder and its complications.
Since women have a better attention to their health and are more accustomed to take care of themselves and their family in general, the majority of participants were women (64.7%).Furthermore, numerous studies have revealed that women report higher rates of preventive and therapeutic health care for chronic and acute conditions than men in this region [30] and in other regions of the world [30] [31] [32] [33] [34].Also, women have got enough time to devote to the follow-up of their diseases due to the fact that the majority of them are unemployed (95.6%).This fact is proved by the shown response to various initiatives and screening campaigns [23].
In this study, we found that 81.1% of diabetics are aged between 50 and 70 years.This can be explained by the fact that 87.5% of diabetics in our sample are type 2, and as is known in the literature, this type of diabetes affects especially adults more than young people [35] [36].
Our results showed that the percentages of illiterate (71.3%) and unemployed (80.6%) people were larger compared to those found (34.4%; 21.5%) in the Eastern region of Morocco in 2014 [37].This may be due to our sample containing mostly women and elderly.
Moreover, 87.5% of diabetic patients in our sample are type 2, which is similar to other findings in previous studies [21] [38] [39].This data can be explained in large part by our sample caracteristics (age 61.0 ± 14.1 years and 50.9% of patients have a diabetes duration less than 10 years).
The results of our study, which took place in the Eastern region of Morocco especially at the Reference Center for Diabetology and Chronic Diseases, reported a high frequency of overweight and obesity in our sample: (43.4% and 28.5% respectively).These results are nearly the same to those found by our team in the same region (40.3% and 25.1%) [23].On the other hand, the proportion of obesity was higher among women (36.1%) compared to men (14.5%).
This huge rate of obesity in women is similar to that found in other studies in Morocco [16] [40] [41].
In the present study, the data concerning the frequency of hypertension is presented in (Table 1).We found the overall frequency of hypertension to be 42.3%.In a report realized by our team [42] in the East of Morocco, revealed a frequency of hypertension of 31.7% in a population aged 40 years and older, and a high frequency (69.9%) in diabetic subjects of the same population.In the same way other studies published a frequency of hypertension ranged between 49.3% and 70.4% among patients with type 2 diabetes in different Moroccan regions [43] [44] [45].These alarming rates of hypertension confirm that this disease has become a scourge of health in our study area like all regions of Morocco.
The pathogenesis of diabetes complications is not fully understood, and controversy exists about why they occur in some patients and not in others.This study was undertaken to define more clearly the risk factors influencing susceptibility to such complications in diabetic patients.In this regard, 32% of the 2401 patients studied had one or more complications.This frequency is lower than the rates obtained in previous studies (63.8% in Morocco (Fez) [45], 60% in Algeria [46], 68.7% in Libya [47] and 86% in Oman [48]).This difference in the frequencies of diabetic complications can be largely explained by the methodology of work of each study and the specific characteristics of the population studied.
In our work, DR is the most frequent complication of diabetes.The prevalence of DR shows wide variations between countries of Northern Africa, ranging from 8.1% to 41.5% [18].In this database, retinopathy was found in 16.8% of patients, which is consistent with previous studies in Arab countries that reported its ranging from 11% to 19% [49] [50] [51].However, our results are inconsistent with other studies, which found higher prevalence of retinopathy among diabetic patients that ranged from 34.5% to 48.6% [52].Besides, DR in the Eastern Mediterranean countries was estimated between 10% -64% [53].
The divergence in the prevalence of retinopathy may be due to differences in the age structure of different populations and to differences in study methodologies and population samples.
The second common complication of diabetes in our sample was the diabetic nephropathy (12.8%).DN results from the same pathological mechanisms as DR, which makes them appear almost at the same time during the disease; the discovery of one of these complications must necessarily lead to the search for the other.
Studies on this microvascular disease reported various rates of prevalence: 10.8% in Saudi [54], 11.6% in Sudan [55] and 13.1% in Tunisia [56].In addition, Afifi and colleagues in Egypt [57] performed multiple cross-sectional study between 1996 and 2001 and showed that DN gradually increased from 8.9% in 1996 to 14.5% in 2001, which is similar to our findings.Other data indicated higher rates than ours (25.2% in Libya, 41.7% in Egypt and 25% in Cameroon) [58] [59] [60].The rate of nephropathy was lower and this could be attributed to the fact that 50.9% of patients had a diabetes duration less than 10 years.
Regarding macrovascular complications in our work, the rate of cardiovascular diseases was 5.4%, similar to that showed in Iran (6.5%) [61].According to some studies realized in the Middle East and North Africa, the macrovascular complications ranged from 9% to 17% in people with diabetes [62] [63] [64].In Montana American Indians the rate of cardiovascular complications was very high (27%) [65].
DOI: 10.4236/ojepi.2018.83014 Our findings showed a low frequency of neuropathy and diabetes foot complications which reached 3.6% and 2% respectively.In other populations, the prevalence of neuropathy ranged from 21.9% to 66% [66] [67] [68].However, a recent study carried out in Iraq [69] reported a prevalence of 2.4% for diabetes foot complications in patients with diabetes which is consistent to our value.The low frequency of neuropathy and diabetes foot complications probably resulted from the good accompaniment and education of the patients by health professionals of (RCD) in the long-term follow-up of their disease.
Our analysis has showed that age, diabetes duration and a high level of albuminuria were the principal risk factors associated with development of diabetes complications in both T1D and T2D.These findings are consistent with other reports [70]- [77] showing that the risk of developing these complications is positively associated with these variables.
This retrospective study confirms previously reported trends in the relationship between hypertension and diabetes complications [72] [75].We have found that hypertension in patients with type 1 and type 2 diabetes was significantly (P < 0.001) associated with development of complications.Furthermore, this association persists after multivariate logistic regression analysis in type 2 diabetes (OR = 1.56; 95% CI: 1.26 -1.92, P < 0.001).
Consistent with foregoing studies [78] [79], we have found that lower levels of education are significantly (P < 0.01) associated with an increased rate of complications in T1D patients and a higher levels of education had a protective effect against diabetic complications in these patients.In the same context, researchers evaluating the relationship between socioeconomic status and diabetic complications indicated that the incidences over 1 to 20 years' follow-up of end-stage renal disease and coronary artery disease were two to three times greater for T1D individuals with lower level of education, compared to those with higher one [79].
In this paper, the risk of each micro and macrovascular complications of T2D is statistically associated with high HbA1c (P < 0.001).33.1% of patients with T2D who have complications, have a poor glyceamic control (HbA1c > 7%).
This result as others [80] [81] [82] has demonstrated that an improved glyceamic control can reduce the incidence and the risk of micro and macrovascular complications in these people.
There is evidence that overweight and obesity are associated with an increased risk of mortality, cardiovascular diseases, and diabetes [12] [83].Our study has confirmed this data and found overweight and obesity to be strongly associated (P < 0.001) with an increased risk for diabetes complications in patients with T1D.

Conclusion
To our knowledge, this is the first study in Eastern Morocco to identify diabetes complications and its risk factors.In this finding, the frequency of diabetes complications is 32%; diabetic retinopathy is the most frequent diabetic complications DOI: 10.4236/ojepi.2018.83014 [14] [15]: usually minor pathways (sorbitol pathway, hexosamine pathway, activation of PKC [protein kinase C], synthesis of advanced glycation products [AGE], irreversibly modifying molecules and proteins by glucose) are overwhelmed and their products damage the cell's balance.
This research was approved by the Moroccan Minister of Health (we obtained authorization to conduct this study from the Regional Director of Public Health in Oujda, representing the Minister of Health in the Eastern Region of Morocco) DOI: 10.4236/ojepi.2018.83014J. Hammoudi et al. and in accordance with the principles embodied in the Declaration of Helsinki.All data were collected from patient records.No individual information including names or initials was published.

Figure 1 .
Figure 1.Types of diabetes complications and their frequencies.
The chi-square test is used for comparison of qualitative variables.

Table 1 .
Descriptive analysis of the total sample according to socio-demographic and bio-clinical settings.

Table 2
N, effective; HbA1c, glycated hemoglobin; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; NS, not significant; P, P-value (comparison the presence of complications with other variables).

Table 3 .
Association of diabetes complications in type 1 and type 2 diabetes with risk factors in logistic regression in univariate analysis.

Table 4 .
Association between diabetic complications in diabetics (T1 and T2) and risk factors with logistic regression in multivariate analysis.

Table 5 .
(a) Distribution of diabetes complications among type 2 diabetic patients by socio-demographic and bio-clinical settings (n = 2101 type 2 diabetic patients); (b) Distribution of diabetes complications among diabetics type 2 by socio-demographic and bio-clinical settings (continued).
N, effective; HbA1c, glycated hemoglobin; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; NS, not significant; P, P-value (comparison the presence of complications with other variables).