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©IDOSR PUBLICATIONS International Digital Organization for Scientific Research ISSN: 2579-0730 IDOSR JOURNAL OF BIOLOGY, CHEMISTRY AND PHARMACY 3(1) 124-146, 2019.

A Systematic Review of the Prevalence and Treatment of Type 2 in Nigeria. Ogochukwu Fidelia Offu

Department of Clinical Pharmacy and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Enugu State University of Science and Technology, Agbani, Enugu State, Nigeria. Email: [email protected]

ABSTRACT Diabetes is on the increase in Nigeria and previous systematic reviews and meta- analysis have reported estimates of the prevalence of Mellitus in Nigeria. However, because of differences in population characteristics, these estimates will vary across and within geopolitical zones. Despite the increase in prevalence of Type 2 Diabetes Mellitus in the country, no other systematic review has been carried out to assess diabetes treatment pattern in Nigeria. Hence, the importance of this study, as it critically reviews the disease prevalence and treatment pattern across and within geopolitical zones in Nigeria.To systematically review all prevalence and treatment studies published from January, 1998 to September, 2018. The following databases were searched for articles: PubMed Central (PMC), African Journal On Line (AJOL), Science Direct, and Connecting Repositories (CORE). Google scholar was also searched. 159 articles were identified from the databases while 12 were identified from Google Scholar. Studies that were excluded are: Studies that dealt mainly the prevalence of Type 1 Diabetes Melitus/gestational diabetes (14); studies with self reported diagnosis (12); case reports and editorials (10); studies that were not representative of the general population (7); and studies without case definitions (8) were excluded from the pool of studies to obtain 38 studies that were utilized for the review. 29 studies were used for the review of prevalence studies while 9 were used for review of treatment/drug utilization studies. For the review of prevalence of diabetes, sample size of studies used for the review of prevalence of diabetes ranged from 105 to 18,921. The South-South region recorded the highest number of studies (10 articles) while the north- east recorded the least number of studies (1 article). The highest prevalence was recorded among Oil company workers in the South-South region (23.4%) while the lowest was recorded among a group of adolescents in the South West region (0.6%). The urban settings had relatively higher prevalence than the rural settings and no particular trend was reported with regard to gender. For the review of treatment of diabetes, the highest number of studies was recorded in the South-West region (4 articles). Sample size ranged from 115 – 349. Only one study from the private facilities was used for this review. Metformin was the most prescribed monotherapy while metformin plus glibenclamide was the most prescribed combination therapy. was also used in dual or triple combination therapy with other oral hypoglycaemic drugs. Prevalence of Type 2 diabetes mellitus is on the increase in Nigeria, especially in the urban settings, among the higher socioeconomic class, and the higher age groups. Treatment of diabetes is in line with most areas of the clinical guidelines except in the area of use of glibenclamide as combination or add-on therapy and with the use of insulin as dual combination therapy.

Keywords: Systematic, prevalence, treatment, diabetes, Nigeria.

INTRODUCTION Life of man for all times and ages has Mellitus constitute one of the most been characterized pathologically by chronic human infirmities of all times. As diseased conditions of which Diabetes a disease of prehistoric era through 124 IDOSR JOURNAL OF BIOLOGY, CHEMISTRY AND PHARMACY 3(1) 124-146, 2019

www.idosr.org Offu antiquity, medieval, modern, and often perceived as mysterious, curse, rare contemporary times, diabetes ravaged disease or evil. Ancient Graeco-Roman humanity for over millennia though medical practices, oriental Chinese and perceived by different ages and peoples Indian traditional medicine, Afro- in diverse ways – at one time as Egyptians papyrus, as well as the peoples mysterious, other times as socio-cultural of Ancient Near East and the Arabian omen, or human affliction. Its impact Peninsula medical civilizations more often emanates from its debilitating characterized the incidence of diabetes pathophysiological effects which have mellitus in one way or the other. Ancient generated over time intense characteristic Indian physicians referred to it as and/or pathological research to unravel madhumeha („honey urine‟) because it and treat the dreaded inferno. attracted ants. Historical Background of Diabetes Around 131-201 CE, Greek physician, Mellitus Galen of Pergamum, theorized diabetes as The term diabetes mellitus etymologically grave affliction of the kidneys. Avicenna derives from the Greek word diabetes (980-1037), a renowned Persian polymath which means to pass through or simply to and physician published “The Canon of siphon while mellitus on the other hand, Medicine” in 1025 in which he provided comes from the Latin word mellitus which unique characterization of diabetes translates to sweet or honey. The literal mellitus as sweet urine, abnormal definition as such is a diseased condition appetite, diabetic gangrene, sexual in humans that cause the siphon or excess dysfunction and frequent urination. He passage of sugar from the body. The also concocted a mixture of seeds (lupin, coinage of the term implicates a medical fenugreek, zedoary) as a panacea to its condition where excess sugar is found in debilitating effects [4]. the blood and in the urine. Literary Other features of diabetes mellitus that accounts differ as to the first scientist pervaded down to medieval age include who coined and used the term. While urine colour, taste, sediment and odour. some accounts refer the initial coinage of This process of disease identification and the term diabetes to Apollonius of examination was referred to as Memphis around 250 BC (Diabetes „uroscopy‟. This was common around the History, 2018); other accounts according 11-12th centuries. Nevertheless, around to [1] “recorded history attributes the first 400–500 A.D., the quest for efficient complete descriptions in the first century diagnostic and pathological knowledge of A.D. to Aretaeus the Cappadocian, who the diabetes mellitus led two great indian coined the word diabetes (Greek, „siphon‟) medical scientists – Sushruta, a physician and dramatically stated “… no essential and Charaka, a surgeon after series of part of the drink is absorbed by the body rigorous scientific studies identified two while great masses of the flesh are types of diabetes – Type 1 and Type 2. liquefied into urine”. [2] On the other However in 1936, Harold Percival hand, the term mellitus was coined by the Himsworth substantially differentiated British Surgeon-General, John Rollo in Type 1 and Type 2 diabetes as unique 1798, in recognition of its sugar-like taste entities as are currently referred in and to differentiate it from diabetes medical science [5]. Further analysis of (insipidus) with tasteless urine [3]. scholarly perspective on diabetes is x- Throughout Antiquity around the 1500 BC rayed in the literature review. and Medieval era, diabetes mellitus was LITERATURE REVIEW The review of extant literature, systematically review topical but relevant perspectives, and scholarly horizons on literature, primary reports and data that the subject of Diabetes Mellitus is focused on the issue. Such reviews aim to important. One of the practical broaden the horizon of knowledge on approaches to deal with the critical issues subject matter, share subjective and of Diabetes is to critically and objective experiences on related issues,

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www.idosr.org Offu investigate and expound the historical diabetes was chronic in some people, it space for evaluating needed facts and was fatal in others; thereby depicting first data. As such, it creates the hypothetical instance of clinical difference among modules for priming and galvanizing our diabetic patients. systematic discourse on Diabetes. However, in 1936 Sir Harold Percival Diabetes – what it is: (Harry) Himsworth characteristically Diabetes is a chronic non communicable distinguished diabetes as type 1 and type disease that occurs either when the 2 as published in his scientific discourse pancreas does not produce enough of the on diabetes. He strongly argued that hormone responsible for regulating the insulin resistance in conjunction with blood sugar in the body and/or a impaired beta-cell function proved the condition where the body cannot major causal factor of type 2 than insulin effectively utilize the hormone referred to deficiency as noted in type 1 diabetes [9]. as insulin. Hyperglycaemia, or raised Type 1 Diabetes Type 1 diabetes known blood sugar, is a common effect of as insulin-dependent, occurs more in uncontrolled diabetes and over time leads children and was often referred to as to serious damage to many of the body‟s juvenile diabetes. Unlike type 2, there is systems, organs and tissues, especially complete insulin deficiency among the nerves and blood vessels [6]. The patients with type 1 and as such are main symptoms of diabetes are three – completely dependent on injection of polydipsia, polyphagia and polyuria – hormone insulin for continued survival. which means increased thirst, increased Although the cause of type 1 diabetes is hunger and increased frequency of still scientifically unknown, symptoms urination. There is also the feeling of include excessive excretion of urine tiredness or fatigue, weight loss and loss (polyuria), thirst (polydipsia), constant of muscle bulk. Type 1 diabetes can hunger, weight loss, vision changes, and develop quickly, over weeks or even days fatigue among others. whereas type 2 diabetes may develop Type 2 diabetes This type of diabetes is gradually [7]. referred to as non-insulin-dependent and Statistically, the prevalence of diabetes occurs more frequently in adults although over decades, despite the multimillion there is currently increasing occurrence in dollar efforts to contain and control the children in view of fast changing lifestyle. disease is a huge concern. It constitutes The major cause of this diabetes is the serious public health challenge not only inability of the body to produce sufficient for health stakeholders and health hormone insulin as needed by the patient. professionals but for international World diabetes statistics reveal that most community. Both the number of cases and people with diabetes have type 2 which the prevalence of diabetes have been occurs more among people who are steadily increasing over the past few obese, overweight or lack regular physical decades. In 2014, 8.5% of adults aged 18 exercise. The symptoms are similar to years and older had diabetes. In 2016, those of type 1 diabetes. diabetes was the direct cause of 1.6 There is increased effort to discover the million deaths and in 2012 high blood exact cause of type 1 diabetes and find glucose was the cause of another 2.2 ultimate cure for all types of diabetes. million deaths [8]. Scientists and academic research Types of Diabetes communities across the world are The search for the cause of diabetes intensely searching for answers to the engaged tens of decades of scientific dreaded scourge of diabetes. Researchers enquiry among scientists, theorists and and medical scientists at Ottawa Hospital medical analysts. In 1776, Matthew and The University of Ottawa are Dobson empirically confirmed that the exploring the role of a bacteria-killing sweet taste found in urine of diabetic protein called cathelicidin antimicrobial patients was a result of the excess sugar peptide (CAMP) found in the pancreas in content. He distinguished that while relation to diabetes. Also the American

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Diabetes Association (ADA) funded series infusion of purified hormone insulin from of research projects aimed at unraveling pancreases of cows to reverse induced greater understanding of diabetes and its diabetes in a 14-year-old boy, Leonard treatment options [10]. Thompson at the Toronto General Gestational diabetes Gestational diabetes Hospital thereby proving scientifically often times occurs among pregnant that insulin deficiency was the primary women with abnormal high blood sugar cause of diabetes and that insulin, as condition. This condition is referred to as coined by de Mayer and Schaefer in 1909 hyperglycaemia. Pregnant women with and 1910 respectively has the capacity to hyperglycaemia have high chances of lower significantly the level of blood developing type 2 diabetes even after glucose (Science History Institute, 2017). delivery. Gestational diabetes is usually Banting and Best made the patent diagnosed during antenatal screening and available free of charge so that millions of pregnant women with this disease diabetics worldwide could get access to condition are at high risk of developing insulin. This led to the mass production health complications during pregnancy of effective treatment for diabetes in and delivery. This condition affects about 1922 and subsequently proved to be life- 4% of pregnant women and is regarded as changing discovery in medical science serious [11]. and in the overall treatment of diabetes Diabetes: Pathophysiological Findings all over the world. It strengthened of 19 – 20th Centuries concerted action and focused research The nineteenth through the twentieth into diabetic and medical actions in centuries recorded hallmark of scientific policy and implementation, changing breakthrough in science and technology. significantly the lives and longevity of More than ever, scientific revolution in ailing diabetic patients and horrendous medical and empirical sciences though threats posed by diabetes across the built on the precipice of preceding world [14]. As a mark of distinction, the breakthroughs gained more insight in World Diabetes Day is celebrated annually precision and reengineering in almost all on November 14 which is the birthday of facets of knowledge. Medical metascience Frederick Grant Banting. witnessed improved outcomes and The ingenuity of Banting and Macleod findings. were acclaimed in a worldwide award of The scientific revolution of the 19th the Nobel Prize in Physiology and century was ripe in medical discoveries Medicine in 1923(Science History and scientific innovations. In 1869, Paul Institute, 2017). There were other Langerhans, a young German anatomist, spectacular Nobel Prizes awards in aged 22 while researching on his Chemistry and Medicine respectively for doctorate identified the cells that were aminoacid sequence [15] and subsequently known as „islets of radioimmunoassay. However, the first Langerhans‟. [12]. In 1889, Von Mering oral antidiabetic drugs (sulphonylureas) and Minkowski, while experimenting on emerged in the 1950s and were dogs, found that inalienable relationship subsequently included in the treatment between pancreas and diabetes. The armamentarium. Others, including experiment showed that the removal of metformin, glucosidase inhibitors and the pancreas from dog led to diabetes and insulin sensitisers, followed in the its complications and eventual death [13]. succeeding decades with different sites of However, in 1921, Canadian researchers, action to enable better handling and Frederick Grant Banting, Charles Herbert metabolic assimilation of ingested Best and James Collip, working in carbohydrates [16]. Macleod‟s laboratory, advanced the works In 1980, the first human insulin was of Von Mering and Minkowski, ligated the manufactured by Graham Bell [17]. In pancreatic duct, causing the destruction 1982, the first biosynthetic insulin of the exocrine pancreas while leaving the (humulin) that is similar in chemical islets intact. They were able through structure with human insulin was

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www.idosr.org Offu developed. Syringes appeared in 1961 families, and the economies but, being made of glass, brought with of nations. People with them the attendant hazards of infections diabetes who depend on until they were replaced with disposable life-saving insulin pay the plastic ones. It was only 15 years later ultimate price when access that the introduction of the first needle- to affordable insulin is free insulin delivery system by Derata in lacking [19].” 1979 provided relatively pain-free, In the United Kingdom, more than two metered doses. Insulin pumps, inhaled million people in the UK have the disease insulin and oral sprays in contemporary condition and up to 750,000 more are times have significantly improved unaware of having the condition. In the administration and therapy [18]. United States 25.8 million people or 8.3% Diabetes epidemiology of the population have diabetes. Of these, Over the years and more conspicuously in 7.0 million have undiagnosed diabetes. In our fast changing time and lifestyle, the 2010 for example, about 1.9 million new scourge of diabetes has become not only cases of diabetes were diagnosed in the problem of the affluent, but population over 20 years. It is strongly increasingly of the middle class and the argued that if this trend goes unchecked, poor. The rate at which diabetes is rapidly it will be most probable that 1 in 3 spreading round the globe among all Americans would be diabetic by 2050. peoples, regions and nations is extremely This is critical and has grave worrisome despite the innovative strides consequences not only on national, in medical sciences. It is now pandemic regional, international, socio-cultural, and demand global response to contain economic and political affairs of nations the ravaging inferno. According to but on the whole survival and longevity of Margaret [19], the Director General of the human race. World Health Organization: According to World Health Organization “Diabetes is on the rise. No (WHO) Fact sheets on diabetes, globally, longer a disease of an estimated 422 million adults were predominantly rich nations, living with diabetes in 2014, compared to the prevalence of diabetes 108 million in 1980. The global is steadily increasing prevalence (age-standardized) of diabetes everywhere, most markedly rose from 4.7% to 8.5% in the adult in the world‟s middle- population since 1980. This reflects an income countries. increase in associated risk factors such as Unfortunately, in many being overweight or obese. The settings the lack of consequences of diabetes in recent times effective policies to create have become not only chronic but supportive environments increasingly fatal. Diabetes caused 1.5 for healthy lifestyles and million deaths in 2012. Higher-than- the lack of access to quality optimal blood glucose caused an health care means that the additional 2.2 million deaths, by prevention and treatment of increasing the risks of cardiovascular and diabetes, particularly for other diseases. Forty-three percent of people of modest means, these 3.7 million deaths occur before the are not being pursued. age of 70 years. The percentage of deaths When diabetes is attributable to high blood glucose or uncontrolled, it has dire diabetes that occurs prior to age 70 is consequences for health higher in low- and middle-income and well-being. countries than in high-income countries In addition, diabetes and its [20]. The basic facts about Global complications impact Diabetes according to WHO Report are harshly on the finances of summarized as follows: individuals and their

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Basic facts The primary role is to direct and  The number of people with coordinate international health within the diabetes has risen from 108 United Nations system which focuses on million in 1980 to 422 million in international public health systems; 2014. health through the life-course;  The global prevalence of diabetes noncommunicable and communicable among adults over 18 years of age diseases; preparedness, surveillance and has risen from 4.7% in 1980 to response, supporting national health 8.5% in 2014. policies and strategies, coordinate the  Diabetes prevalence has been efforts of governments and partners – rising more rapidly in middle- and including bi- and multilaterals, funds and low-income countries. foundations, civil society organizations  Diabetes is a major cause of and the private sector and corporate blindness, kidney failure, heart services (WHO, 2018). As coordinating attacks, stroke and lower limb authority on international health within amputation. the United Nations, WHO works on the  In 2016, an estimated 1.6 million following programme specific areas: deaths were directly caused by diabetes. Another 2.2 million deaths were attributable to high blood glucose in 2012.  Almost half of all deaths attributable to high blood glucose occur before the age of 70 years. WHO estimates that diabetes was the seventh leading cause of death in 2016.  Healthy diet, regular physical activity, maintaining a normal body weight and avoiding tobacco use are ways to prevent or delay the onset of type 2 diabetes.  Diabetes can be treated and its consequences avoided or delayed with diet, physical activity, medication and regular screening and treatment for complications [21]. WHO Intervention World health Organization (WHO) is an international agency of the United Nations Organization. It was constitutionally created by the United Nations on April 7, 1948 to respond to growing need for global health and sustainable livelihood. WHO is working with 194 Member States, across six regions, and from more than 150 offices, and with a workforce of over 7000 people across the world who are united in a shared commitment to build a better, healthier future and secured health for everyone, everywhere. The headquarters is in Geneva, Switzerland.

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International Health systems World Preparedness, surveillance and Health Organization prioritizes public response During emergencies, WHO‟s health systems and is moving towards operational role includes leading and universal health coverage. WHO works coordinating the health response in together with policy-makers, global health support of countries, undertaking risk partners, civil society, academia and the assessments, identifying priorities and private sector to support countries to setting strategies, providing critical develop, implement and monitor solid technical guidance, supplies and financial national health plans. In addition, WHO resources as well as monitoring the health supports countries to assure the situation. WHO also helps countries to availability of equitable integrated strengthen their national core capacities people-centred health services at an for emergency risk management to affordable price; facilitate access to prevent, prepare for, respond to, and affordable, safe and effective health recover from emergencies due to any technologies; and to strengthen health hazard that pose a threat to human health information systems and evidence-based security. policy-making. Corporate services Corporate services Non communicable diseases Non provide the enabling functions, tools and communicable diseases (NCDs), including resources that make all of this work heart disease, stroke, cancer, diabetes and possible. For example, corporate services chronic lung disease, and mental health encompasses governing bodies, conditions - together with violence and convening Member States for injuries - are collectively responsible for policymaking, the legal team advising more than 70% of all deaths worldwide. during the development of international Eight out of 10 of these deaths occur in treaties, communications staff helping to low- and middle-income countries. The disseminate health information, human consequences of these diseases reach resources – bringing in some of the beyond the health sector and solutions world‟s best public health experts and/or require more than a system that prevents building and promoting valuable services. and treats disease. With respect to non communicable Promoting health through the life- diseases, particularly diabetes, WHO aims course Promoting good health through to stimulate and support the adoption of the life-course cuts across all work done effective measures for the surveillance, by WHO, and takes into account the need prevention and control of diabetes and its to address environment risks and social complications, particularly in low and determinants of health, as well as gender, middle-income countries. To this end, equity and human rights. The work in this WHO: biennium has a crucial focus on finishing 1. provides scientific guidelines for the agenda of the Millennium the prevention of major non Development Goals and reducing communicable diseases including disparities between and within countries. diabetes; Communicable diseases WHO is working 2. develops norms and standards for with countries to increase and sustain diabetes diagnosis and care; access to prevention, treatment and care 3. builds awareness on the global for HIV, tuberculosis, malaria and epidemic of diabetes, marking neglected tropical diseases and to reduce World Diabetes Day (14 vaccine-preventable diseases. MDG 6 November); and (combat HIV/AIDS, malaria and other 4. conducts surveillance of diabetes diseases) has driven remarkable progress and its risk factors. but much work remains. The WHO "Global report on diabetes" provides an overview of the diabetes burden, the interventions available to prevent and manage diabetes, and recommendations for governments,

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www.idosr.org Offu individuals, the civil society and the Prevention of Diabetes private sector. WHO maintains that as WHO advocates for effective mechanisms part of the 2030 Agenda for Sustainable and approaches that can prevent the Development, member countries have set incidence and significantly mitigate the an ambitious target to complications of diabetes (Type 2) and (a) reduce premature mortality from need for concerted efforts in critical NCDs – including diabetes – by one third; research and development. These include (b) achieve universal health coverage and, policies and practices across whole (c) provide access to affordable essential populations and within specific settings medicines – all by 2030. (school, home, workplace) that contribute In the same vein, WHO "Global strategy on to good health for everyone, regardless of diet, physical activity and health" focuses whether they have diabetes, such as on population-wide approaches to exercising regularly, eating healthily, promote healthy lifestyle including good avoiding smoking, and controlling blood and affordable diet and regular physical pressure and lipids. activity, thereby reducing the growing Lifestyle changes and implementing global problem of overweight and obesity proactive life-course perspective are among peoples [22]. paramount to preventing type 2 diabetes Impact of Diabetes as well as other health conditions. It is Diabetes has serious consequences and vital to make this lifestyle changes and exerts enormous impact on both the proactive life-course programmes early in patients‟ health and socioeconomic life when eating and physical activity relations and the entire human habits are formed and when the long-term community. Complications arising from regulation of energy balance may be the overall health risk may include programmed. This will enhance needed general morbidity, heart attack, stroke, intervention to mitigate the risk of kidney failure, leg amputation, vision obesity and type 2 diabetes later in life. loss, nerve damage and eventual painful This is a key prevention mechanism not death. In pregnancy, poorly controlled only for diabetes but for most critical diabetes increases the risk of fetal death health conditions. [24]. and other complications even to the Intervention/Management of Diabetes pregnant mother. Intervention is an integral policy Apart from its direct economic toll on the framework that is targeted and patients, its socioeconomic impact on implemented timely and early in life. No aggregate economy of family and friends, single policy or intervention programme community and nation, health system and can ensure total success. It calls for a providers including the ever fluctuating whole-of-government and whole-of- price of drugs and administration abound. society approach in which all sectors WHO indicates that while the major cost systematically consider the health impact drivers are hospital and outpatient care, a of policies in trade, agriculture, finance, contributing factor is the rise in cost for transport, education and urban planning – analogue which are increasingly recognizing that health is enhanced or prescribed despite little evidence that obstructed as a result of policies in these they provide significant advantages over and other areas. cheaper human insulins. In most The key to successful management of developing and poor income countries diabetes and other critical NCDs is early with analogue and grossly insufficient, diagnosis – the longer a person lives with inefficient and unregulated healthcare undiagnosed and untreated diabetes, the systems and policy frameworks, the worse the health outcomes and situation is more precarious for all types complications. As such, easy access to of diabetic conditions than in advanced basic diagnostics, such as blood glucose economies with comparatively advanced testing, should be made available in healthcare systems and providers [23]. primary health-care centres in rural and urban settings. Effective referral systems

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www.idosr.org Offu and clinics are needed, as patients will treatment of diabetes should occur in the need periodic specialist back-and-forth context of integrated non-communicable assessment or treatment for disease (NCD) management to yield better complications. For those who are outcomes. At a minimum, diabetes and diagnosed with diabetes, a series of cost- cardiovascular disease management can effective interventions can improve their be combined. Integrated management of outcomes, regardless of what type of diabetes alongside other critical health diabetes they may have. These conditions should be considered. interventions include blood glucose Intervention especially in low-income control, through a combination of diet, countries should include national physical activity and, if necessary, capacity and political will to provide medication; control of blood pressure and critical health facilities in rural and urban lipids to reduce cardiovascular risk and settings, access and availability to other complications including regular affordable drugs, provision and access to screening for damage to the eyes, kidneys basic technologies needed to help people and feet. with diabetes properly manage their Diabetes management can be disease, funding and effective policy strengthened through the use of implementation and overall capacity standards and protocols. Efforts to building for healthcare professionals and improve capacity for diagnosis and stakeholders. METHODS Study Selection v. hospital based studies that listed the Search for articles written in English was drugs that were used for the treatment of carried out using PubMed Central (PMC), type 2 Diabetes Mellitus and their African Journal On Line (AJOL), Science utilization rates in percentages. Direct, Connecting Repositories (CORE) Exclusion Criteria and Google Scholar. The search was Studies that were excluded from this limited to studies carried out from 1998 review were: to 2018. MeSH headings were used to i. Studies that were carried out to search for the following terms: „diabetes determine the prevalence of type 1 mellitus‟, „prevalence‟, „treatment‟, and diabetes only or gestational diabetes. „Nigeria „ including related words like ii. Studies in which diagnosis of diabetes „management‟, „glucose metabolic was based on self reporting. disorder‟, and „hyperglycaemia‟. ii. Studies that were carried out before Bibliographies of each article were also 1998 and after September 2018. searched to in order to identify other Ethical approval articles could be included in the study. This study was not carried out directly on The last search was carried out on the 30th humans but made use of cross-sectional day of September, 2018 and a total of 43 and hospital based studies that were studies were included in this review. carried out by other researchers. Hence, there was no need to obtain ethical Inclusion Criteria clearance from an Ethics Committee. Studies that were included in this review Case Definition were: The diagnostic criteria used in the i. population studies, hospital and clinic prevalence study were: based studies in which FPG, RPG, OGTT, i. Fasting Plasma Glucose ≥ 126 mg/dl or HBA1c was used as basis for (7mmol/l). Fasting refers to no caloric diagnosing diabetes. intake for at least 8 hours. ii. studies that were carried out between ii. Random Plasma Glucose ≥ 200mg/dl 1998 and 2018. (11.1mmol/l) in patients with classic iii. studies that reported prevalence rates symptoms of hyperglycemia or of type 2 diabetes mellitus. hyperglycemic crisis, iv. studies that consisted of populations iii. Plasma glucose 2 hour post-glucose that were aged 2 years and above. load (75g) ≥ 11.1 mmol/l. A glucose load

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www.idosr.org Offu that contains the equivalent of 75 g diabetes only or gestational diabetes (14 anhydrous glucose dissolved in water articles). should be used and carried out as b. Studies in which diagnosis of diabetes described by the World Health was based on self reporting (12 articles). Organization c. Studies that were case reports, and iv. Glycated Haemoglobin (HbA1c) ≥ 6.5% editorials (10 articles). (WHO, 1999 ; ADA, 2010). The test should This further reduced the number of be performed in a laboratory using articles left for review to 53. The full text methods that are NGSP (National articles of these 53 studies were then Glycohemoglobin Standardization assessed for eligibility and 15 were Program) certified and standardized to excluded due to the following reasons: the DCCT (Diabetes Control and a. studies that were not representative of Complications Trial) assay. the general population in which the study Study Selection was carried out (7 articles). Databases searched were PubMed Central b. studies without case definitions (8 (PMC), African Journal On Line (AJOL), articles). Science Direct, and Connecting Finally, the 38 studies left were then used Repositories (CORE). Google scholar was for the systematic review. This process is also searched. As shown in the PRISMA described in the PRISMA Chart displayed flow chart (Figure 2.1), 159 studies were below (Figure 2.1). identified from all database searches Data Collection which consists of PMC (71articles), AJOL A modified Data extraction form was used (73 articles), Science Direct (13 articles) to extract data. This extraction form was and CORE (2 articles). pilot tested with the first 10 studies In addition, 12 articles were identified assessed. Items that were extracted from from Google Scholar Searches. In all, 171 each study include: year of study, articles were identified out of which 82 state/geopolitical zone where the study were duplicates of previously identified was carried out, age of the study studies and were removed from the pool participants, sampling method, sample of studies. The abstracts of the remaining size, response rate, setting, case 89 studies were screened and 36 of them definition, and prevalence of diabetes. did not meet the inclusion criteria and Data was extracted by the main researcher were excluded from the pool of studies. and a co-researcher and where there were Studies that were excluded include: obscurities, both researchers clarified a. Studies that were carried out to them through useful discussions. determine the prevalence of type 1

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Records identified from database Additional records identified from search: 159 articles Google Scholar:

PubMed Central- 71 articles GoogleScholar-12 articles AJOL – 73 articles Science Direct- 13 articles CORE- 2 articles

Duplicates that were identified and removed=82 articles

Records after duplicates were removed = 89 articles Abstracts that were assessed and

removed=36 articles :

a. Studies that were carried out to determine the prevalence of type 1 diabetes only or gestational diabetes.= 14 b. Studies in which diagnosis of diabetes was based on self reporting.= 12 c. Studies that were case reports, and editorials.= 10 Assessment of full text articles = 53 articles

Articles that were identified and removed=15 articles : a. studies that were not representative of the general population in which the study was carried out (7 articles). b. studies without case definitions (8 articles)

Studies included in the review = 38 articles

Prevalence Studies=29 articles

Treatment of diabetes studies=9 articles

Fig 1: Flow Chart of the Studies included in the Systematic Review

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Synthesis and Statistical Methods studies to give a wider view of the No statistical analysis was carried out problem in Nigeria. because this study is a systematic review. Analysis of the treatment data was more We were interested in describing the of a narrative synthesis which describes changes in prevalence data across the types of antidiabetic drugs that are different geopolitical zones of Nigeria and used in Nigeria and their utilization in critically appraising the included pattern. Hence, no statistical analysis was carried out. RESULTS Thirty eight independent studies were out in all the states and capital of included in this review. Twenty nine Nigeria. studies were prevalence studies while The included studies were generally large; nine studies were articles that dealt with the community studies that were carried the treatment of diabetes in Nigeria. out were 22, the hospital based studies These studies were published between the were 4 ; Secondary school was 1, Staff of year 1998 and 2018. University was 1 and 1 study was carried Systematic Review of Prevalence of out amongst oil company staff together Type 2 Diabetes Mellitus with some university students/staff. Table 1 shows the characteristics of all Sample sizes of studies ranged from 105 studies included for this review with the to 18,921. The setting where the studies prevalence were conducted included urban (14 of diabetes reported for each study. studies), rural (8 studies), mixed (ie both Twenty nine studies were conducted rural and urban populations were used- across the 6 geopolitical zones of Nigeria. 3studies) including semi urban (4 The numbers of studies carried out in studies). each zone include: south- south (10 The age of participants ranged from 1 to articles), south-west (8 articles) south- 102 years old. Only 1 study was carried east (4 articles), north-central (3 articles); out solely on the adolescent age group- 10 north-west (2 articles) , north-east (1 to19 years old with a prevalence of 0.6%. article), and 1 study which was carried The highest prevalence was 23.4% in the South-South region.

Table 1 Characteristics of all studies included in the Systematic Review for Prevalence Study Prevalence(%) First Diagnosti Age Sampl S/N Author Setting Year c method Range/ e Size General Male Female Mean SOUTH-SOUTH

1. Nwafor A Urban 2001 FPG, RPG 17 – 60 403 High SES- 7.63 8.4

Oil company 23.4% staff; university students and Low SES - staff 16%

2. Nyenwe E.A Rural/ Urban 2003 RPG >40 502 6.8 7.7 5.7 Community 2hr-Pg

3. Ojehanon P. Urban 2006 FPG 15 – 75 1570 4.5 57.1 42.9

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Hospital

4. Unachukwu Urban 2008 FPG,RPG ≥ 10 6574 10.4 62.4 37.6

C.N Hospital

5. Ekpenyong Urban 2012 RPG, FPG 18-60 3500 12.7 9.7 16.0 C.E Community 2hr-pG 6. Enang O.E Urban 2014 FPG/RPG ≥ 15 1134 6.5 7.1 4.7

Community

7. Alikor C.A Rural 2015 FPG 41.32 ± 17 500 2.2 2.6 2.0

Community

8. Okafor U.H Rural 2015 RPG ≥ 18 105 8.1

Community 9. Isara A.R Rural 2015 FPG 18 – 90 845 4.6 1.9 5.8 Community 10 Oguoma V.M Rural/ Urban 2017 FPG 18-89 2447 3.1 Nr Nr

Community SOUTH-WEST

11 Olatunbosun Urban 1998 2hr-pG ≥ 15 875 0.8 57 42.9 P.O Community

12 Adebayo A.M Urban 2011 RPG ≥ 2 302 3.0 3.1 2.9

Community

13 Ayodele O.E Urban 2011 FPG/RPG 42.4 ± 586 3.8 59.1 40.9

Community 11.2

14 Ogunmola Rural 2013 FPG ≥ 40 104 4.8 0 7 O.J Community

15 Oluyombo R. Semi-Urban 2014 FPG ≥ 18 750 6.8 8.6 6.0

Community 16 Oluwayemi Semi-Urban 2015 FPG 10 – 19 628 0.6 Nr Nr

O.I Community

17 Adeoti A.O Urban 2015 FPG, RPG, 16 – 102 3,750 18 Nr Nr 2hr-pG Hospital

18 Rasaki O.S Rural 2017 FPG ≥ 18 10,000 4.6 6.3 93.7 Community

SOUTH-EAST

19 Okafor C.N Rural 2014 FPG ≥ 18 137 8.8 * 8.8 community 136 IDOSR JOURNAL OF BIOLOGY, CHEMISTRY AND PHARMACY 3(1) 124-146, 2019.

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20 Ejike C.C Semi-Urban 2015 FPG 30 – 74 365 3.0 2.3 3.6 Community 21 Adogu P Urban 2015 FPG/RPG ≥ 1 18912 10.7 52.1 47.9 Hospital 22 Okwuonu Semi-Urban 2017 FPG/RPG <20-≥60 328 7.9 7.2 8.5 C.G community

*only women were used in this study

NORTH-CENTRAL

23 Puepet Urban 2008 2hr-pG ≥ 15 902 4%

Community

24 Etukumana E Rural 2013 FPG,RPG ≥15 750 4.1 5.2 3.0

Community

25 Agaba E.I Urban 2017 FPG ≥ 18 883 8% 6.9 9.7 University staff NORTH-WEST

26 Bello-Ovosi Urban 2018 RPG 23 – 87 181 23.3 9 33

B.O Community

27 Sabir A. Rural 2013 FPG,RPG,2 18-95 393 0.8 0.3 0.5 community hr-Pg

NORTH-EAST

28 Gezawa I.D Urban 2015 FPG 15-70 242 7.0 10.4 4.8 Community ACROSS ALL STATES AND THE CAPITAL

29 Kyari F. Rural/Urban 2014 RPG ≥ 40 13,591 3.3 3.9 2.7 Community

Systematic Review of the Treatment of facility. The sample size of the studies type 2 Diabetes Mellitus used in this review ranges from 115 to Table 2 displays relevant information 349. The studies were carried out about the studies included for the review. between 2006 and 2017. Oral antidiabetes 9 studies were used in carrying out the medications were generally more used systematic review. All studies were than insulin with rates of 71% in UCH, carried out across 4 regions of the 85.7% in OAUTH and 76.5% [25]; [26]. The country. 4 of the studies were carried out utilization rates of insulin were 26.4%, in the South-West while only 1 study was 2.5%, 8.2%, 0.6% and 7.7% [27]. Out of all 5 carried out in the South-East region, studies in which utilization rates of North-Central and North-East regions biguanide/metformin was reported, 4 respectively. 6 of these studies were studies reported that the carried out in Teaching Hospitals, while 1 Biguanides/metformin were the most study was carried out in a private health utilized of all the antidiabetic

137 IDOSR JOURNAL OF BIOLOGY, CHEMISTRY AND PHARMACY 3(1) 124-146, 2019.

www.idosr.org Offu medications, with utilization rates of (4.2%) [22]. 2 studies reported the 65.9%, 55.8%, 58.7%, and 76.9% [12]; [13]; percentage of patients that were [14]; [15]. Only 1 study reported low prescribed more than 4 medicines as utilization rate of biguanide/metformin 55.2%, 53.3% and 73.0% [1]; [3].

Table 2 Studies included in the Systematic Review for treatment of Type 2 Diabetes Study First Setting Year Study Sample Drugs Prescribed Drug utilization Author Design Size (%) 1 Enwere UCH 2006 Cross- 349 Biguanides 65.9 O.O Sectional Sulphonylureas 54.2

Insulin 26.4

2 Uwakwe Private 2009 Retrospective 120 Biguanide only 4.2 J.N Health Facility in Jos Sulphonylurea alone 18.3

Biguanide + sulphonylurea 60.8

Biguanide + sulphonylurea + 3.3 thiazolidinedione Insulin + biguanide 10.8

Insulin alone 2.5

3 Adisa R. UCH & 2013 Cross 170 OAM 76.5% OAUTH sectional OAM + Insulin 15.3%

Insulin alone 8.2%

Single OAM

Metformin 9%

Glimepiride 1.3%

Others: 0% Glibenclamide, gliclazide, Rosiglitazone, Pioglitazone, voglibose, acarbose Glyburide/Metformin (Fixed) 1.3

Glimepiride/Metformin (Fixed) 1.3

Pioglitazone/Metformin 8.4 (Fixed)

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Glibenclamide + Metformin 33.4 (Nonfixed/co-administered) Glimepiride + Metformin 23.9 (Nonfixed/co-administered) Glimepiride + Pioglitazone 1.2 (Nonfixed/co-administered) Gliclazide + Metformin 0.6 (Nonfixed/co-administered) 3- OAM combination

Glimepiride + Metformin + 12.9 Pioglitazone Glibenclamide + Metformin 7.1 +Pioglitazone 4 Ogbonna NAUTH 2014 Retrospective 286 Metformin 55.8 B Glibenclamide 35.1

Pioglitazone 6.8

Glimepiride 1.0

Gliclazide 0.8

Insulin 0.6

5 Fadare J LAUTH 2015 Cross- 129 Metformin 58.7 Sectional Glibenclamide 25.9

Glimepriride 13.8

Vidagliptin 1.1

Pioglitazone 0.5

Combination Oral 57.4 Hypoglycaemic Agent(OHA) therapy OHA and insulin 14

Metformin only 11.6

UCH OAUTH

6 Adisa R. UCH & 2016 Prospective 185 OAM 71 85.7 OAUTH OAM + Insulin 15.9 14.3

Insulin alone 13.1 0%

≤ 4 meds 46.7 27.0

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>4 meds 53.3 73.0

Generic versus proprietary prescription Exclusively generic 71.7 39.7 medications Exclusively proprietary 12.3 15.9 medications Generic plus proprietary 16 44.4 medicine 7 Okoro UMTH 2017 Retrospective 115 Monotherapy 22.6% R.N Maiduguri n=26 .

Metformin 76.9

Glimepiride 7.7

Vildagliptin 7.7

Insulin 7.7

Dual Therapy n =74 64.35%

Metformin,Glibenclamide 63.5

Metformin,Glimepiride 21.6

Metformin,Vildagliptin 9.5

Glibenclamide,Vildagliptin 2.7

Metformin,Insulin 2.7

Triple therapy n =3 2.61%

Metformin, Glibenclamide, 33.3 Insulin

Metformin,Glibenclamide,Piog 33.3 litazone Metformin,Glibenclamide,Vild 33.3 agliptin

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Fixed Dose Combination 10.43% n = 12

Metformin + Glibenclamide 66.7

Metformin + Vildagliptin 33.3

8 Olurishe C ABUTH 2012 Retrospective 110 Sulphonylureas 1.81

Biguanides 10

Sulphonylureas/ 49.09 Biguanides

Sulphonylureas/ 17.27 biguanides/glitazones

Fixed dose(Sulphonyl 8.18 Ureas/Biguanides)

Insulin/oral hypogly 10.90 caemic agents Insulin 2.72

9 Jimoh A UDUTH 2012 Cross- 348 Metformin+Glibenclamide 76.7 Sectional Metformin+Glibenclamide+pio 10.6 glitazone Metformin+Glibenclamide+ins 5.2 ulin Metformin+pioglitazone 3.7

Metformin+insulin 0.9

Metformin + Gliclazide 2.0

Pioglitazone + Glibenclamide 0.9

Nr-not reported

DISCUSSION Studies were carried out in the south than rural areas/ areas of lower socioeconomic the north. Similar findings have been class. This is as a result of urbanization reported in a review carried out by [7]. In which results in sedentary lifestyle and addition, the urban areas/areas of higher poor diet in the urban areas. Similarly, socioeconomic status recorded higher this same finding was reported in a prevalence of diabetes mellitus than the review carried out by [4]. 140 IDOSR JOURNAL OF BIOLOGY, CHEMISTRY AND PHARMACY 3(1) 124-146, 2019.

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The highest prevalence recorded in this parts of the world where metformin is review was from the south-south zone also the most utilized antidiabetic [9]. with a prevalence of 23.4% among the However, in some other studies, workers of the Agip Oil Company, Port sulphonylureas where the most Harcourt [2]. On the other hand, the prescribed class of antidiabetics [18] lowest prevalence occurred among In this review, studies that reported use Secondary School adolescent students in of combination therapy, recorded that the the South West Zone with a prevalence of combination of biguanide (metformin) 0.6% [8]. and sulphonylurea (glibenclamide) were Only 3 of the 29 studies included in this the most prescribed. In the same vein, it systematic review had prevalence rates has been reported that metformin and (0.8%, 0.6%, 0.8%) that were lesser than glibenclamide were the most prescribed the prevalence rate of 2% that was antidiabetics in other studies carried out reported by the IDF [4]; [5]; [6]. This in Brazil and India [15]; [16]. On the shows that reports from the IDF which are contrary, in some other countries, usually gotten from projections of metformin plus glimepiride is more used prevalence rates in countries may actually than metformin plus glibenclamide [12]; underestimate the true prevalence of the [13]. Also, majority of patients were disease in Nigeria. prescribed more than 4 medications. It was also observed that there was a Combination of oral antidiabetic dearth of studies carried out in the medications were used more than the Northern part of the country especially in combination of Oral Antidiabetic the North-East region. Hence, researchers Medications and Insulin. This result was should be motivated by policy makers to similar to results gotten from an carry out studies that focus on antidiabetic drug utilization study carried determining the prevalence of diabetes in out in India by [15]. In Mandal‟s study it this geopolitical zone. was reported that Oral hypoglycemic In general, the age groups with the agents were preferred to Insulin as highest prevalence rates were reported to monotherapy as well as in combination be: ≥ 35 years ,41-50 years, 45 – 64 years, with other oral hypoglycemics. Similarly, 51 – 60 years, 55 – 64 years and 61- 70 another study reported that dual years [1]; [2]; [3]; [4]; [5]; [7]. On the other combination therapy was prescribed more hand, the lowest prevalence rates were than combination of oral hypoglycaemics recorded in the following age groups: 1- and insulin [17]. 10 years & 11 – 20 years, < 20 years, 25 – As observed in our review, proprietary or 34, < 30 years, < 35 years and < 45 years brand prescribing was also practiced at [9]. UCH and OAUTH but the frequency of its With regards to prevalence in females and practice was recorded in less than one males, no specific trend was noticed, that quarter of all the prescriptions studied in is, no remarkable difference between the each of these hospitals [24]. Similar result prevalence pattern in males and females was recorded by Sarumathy et al in was observed between these 2 groups. another study carried out in India [27]. Discussion for the treatment of diabetes Results that are not similar to that mellitus reported in our study has also been Biguanide (Metformin) was the most recorded in India in which majority of prescribed of all medications used in drugs prescribed were in their brand treating Type 2 Diabetes Mellitus (either names [25]. In fact, in 2 other studies singly or as a combination) in all the carried out in India and Bangladesh, all studies carried out in teaching hospitals the drugs prescribed were written in their except for the private health facility brand names [3]; [4]. where the sulphonylureas (when used In addition, this review revealed that singly) were the most prescribed oral about 10% of all drugs prescribed in the antidiabetic medication. This is in University of Maiduguri Teaching Hospital tandem with what is obtainable in other were fixed dose combination drugs.

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However, in some studies carried out in elderly who are at high risk of other climes, the fixed dose combination hypoglycaemia. preparations were the most prescribed Some of the studies reviewed, used [7]; [8]; [9]. Fixed dose combination insulin as one of the drugs in their dual preparations will reduce pill burden and antidiabetic combination therapy [7]This improve adherence but cost and practice is not in line with that projected affordability should be considered when by the IDF. The IDF recommends the use prescribing FDC preparations. of 2 oral hypoglycaemic agents and it also In conclusion, the result from our study states that insulin should only be added reveals that the drugs prescribed for Type to make up a triple therapy. The IDF also 2 Diabetes Mellitus in Nigeria is in line recommends the use of 3 oral with current International Diabetes hypoglycemic agents. Federation (IDF) Clinical Practice In addition, the IDF supports the use of Recommendations for managing Type 2 fixed combination therapy whenever Diabetes in Primary Care. However, this possible since it promotes patient‟s IDF document also states that adherence to therapy (IDF, 2017). sulphonylureas are appropriate as However, majority of Nigerians may not combination or add-on therapy, except for be able to afford fixed combination glyburide or glibenclamide (IDF, 2017). therapy. The low use of fixed Studies have also been carried out in combination therapy observed in this support of this recommendation. A study review may be because of its high cost. carried out by Riddle revealed that early Since diabetics are meant to be on their mortality with the use of medication for a lifetime, the cost of their glyburide/glibenclamide was almost 3- medication is a very crucial factor in their fold higher than when glimepiride or management and hence health gliclazide were used [21]. In other studies, practitioners should take cost into glyburide/glibenclamide was also consideration when prescribing associated with a higher risk of antidiabetic drugs. This is very important hypoglycaemia than other sulphonylureas in a country like Nigeria where the like glipizide or glimepiride [10]; [11]. minimum wage of her citizens is $49 and Hence, caution should be exercised by where there is minimal health coverage Nigerian practitioners when considering for her masses- less than 5% of Nigerians the use of glyburide/glibenclamide in have health insurance coverage [20]. treatment of their patients, especially the CONCLUSION Generally, the prevalence of Type 2 The treatment of Type 2 Diabetes is in Diabetes Mellitus is on the increase in tandem with current treatment guidelines Nigeria, most especially in regions of in most areas, but care and caution higher socioeconomic status and in the should be taken in these specific areas urban areas. Type 2 Diabetes Mellitus is that are not recommended by the also more prevalent in older age groups guidelines, though are practiced by than in the younger age groups. majority of the health practitioners in Notwithstanding, Diabetes Mellitus was Nigeria: also observed among some adolescents in i. use of glibenclamide/glyburide either the South-West zone. In addition, no as combination or add-on therapy with particular trend was observed when metformin. prevalence in males and females were ii. use of insulin in dual combination compared. therapy. RECOMMENDATION 1. The Research Institutes should carry Diabetes Mellitus. More prevalence out more researches in the area of studies carried out in different regions of prevalence and treatment of Type 2 Nigeria will provide evidence that will Diabetes Mellitus regularly as this will enable the policy makers to better plan help in reducing the prevalence of Type 2 budgets that are specific to the medical

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www.idosr.org Offu needs of a particular region. In the same individuals can exercise themselves vein, more treatment/drug utilisation should be set up by the Government. All studies should be carried out so that these will help to curb the increasing lapses in our treatment protocols are prevalence of obesity which is a risk easily noticed and corrected so as to factor to Type 2 Diabetes Mellitus. The ensure proper management of diabetic Government can also increase the tax paid patients in Nigeria. by alcohol breweries and industries that 2. Therapeutic Committees should be produce food items that predispose reinvigorated and mobilized to carry out individuals to Type 2 Diabetes Mellitus. routine critical assessment of Type 2 This will prevent people from purchasing diabetic patients prescriptions. This will these products since the cost of enhance and enable the prompt detection purchasing these items will also be high and correction of prescription errors. In 5. Since diabetic patients have to be on the long run, it will reduce significantly their drugs for as long as they live, the the patient‟s risks of developing Government should organize a special complications (and burden to the society) type of insurance program for them. This that arise from Type 2 Diabetes Mellitus. will enable them take their drugs as 3. The policy makers should encourage required and thus reduce their risk of intercollaboration between the Ministry of developing complications and thus will Education, Ministry of Health, and help reduce the burden of the disease in Ministry of Agriculture towards Nigeria.. combating the incidence of Type 2 6. The capacity of the ministries of health Diabetes Mellitus. Campaigns and should be strengthened to exercise a Seminars should be organized aimed at strategic leadership role and engage promoting healthy lifestyle and stakeholders across various sectors and preventing the disease among Nigerians. society. Set national targets and Topical issues such as proper diet, indicators to foster accountability. Ensure importance of exercise/dangers of living a that national policies and plans sedentary lifestyle, early detection and addressing diabetes are fully costed and screening, recognition of signs and then funded and implemented. symptoms of the disease and 7. Strengthen the health system response complications of the disease should be to NCDs (Non Communicable Diseases), highlighted. The target population should including diabetes, particularly at also include children and not only adults primary-care level. Implement guidelines because in recent times, Type 2 Diabetes and protocols to improve diagnosis and have also been detected in children. management of diabetes in primary 4. The Government should create an health care. Establish policies and enabling environment that will help in programmes to ensure equitable access to fostering a healthy lifestyle. E.g. in the essential technologies for diagnosis and workplace and schools, specific periods management. Make essential medicines should be set aside for exercise; time for such as human insulin available and games should be set aside in the schools; affordable to all who need them. fields and pedestrian tracks where REFERENCES 1. Adeloye, D., Ige, J., Aderemi, A., 2. Allan, F. Diabetes before and after Adeleye, N., Amoo, E., Auta, A., insulin. Med Hist. Jul; 16 (3): 266 – and Oni, G. (2017). Estimating the 273. Retrieved from prevalence, hospitalisation and https://www.ncbi.nlm.nih.gov/pm mortality from type 2 diabetes c/articles/PMC1034981/. Accessed mellitus in Nigeria: a systematic on 3rd September, 2018 review and meta-analysis. British 3. American Diabetes Association. Medical Journal Open ;7:e015424. (2010). Diagnosis and doi:10.1136/bmjopen-2016- classification of diabetes: diabetes 015424. care. Diabetes Care.;33(Suppl

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