Diabetes was first documented by the Egyptians and is characterized by weight loss and polyuria. However, it was the Greek physician Aertaeus who coined the term diabetes mellitus (DM). In Greek, diabetes means "to pass through" and mellitus is the Latin word for honey (referring to sweetness). Diabetes is an important cause of prolonged ill health and premature mortality and claims more lives per year than HIV-AIDS with nearly 1 death every 10 seconds.
DM is a kind of metabolic disease. Defects in insulin secretion, insulin action, or both lead to its characteristic, hyperglycemia. It is important for insulin, as an anabolic hormone, to metabolize Carbohydrates, Lipids, and Proteins. Low levels of insulin to achieve adequate response and/or insulin resistance of target tissues, mainly skeletal muscles, adipose tissue, and to a lesser extent, liver, at the level of insulin receptors, signal transduction system, and/or effector enzymes or genes are responsible for these metabolic abnormalities.
The ADA has recently incorporated Glycosylated hemoglobin A1c not only as a measure of the control of hyperglycemia and efficacy of interventions but also as a diagnostic test for DM. A value of 48 mmol/mol (6.5%) is a type of diagnosis of DM. The severity of symptoms depends on the type and duration of the disease. Some patients have no symptoms such as those patients who suffer from type 2 diabetes at the early stage of the disease. Others with obvious hyperglycemia and especially in children with absolute insulin deficiency may suffer from polyuria, polydipsia, polyphagia, weight loss, and blurred vision. Once diabetes is not controlled, it may result in stupor, coma, and if not treated death, due to ketoacidosis or rare nonketotic hyperosmolar syndrome.
In the human body, several systems and pathways function in synchrony to bring about and maintain a healthy physiological state. At the core of these processes lies the ability of the organism to maintain a constant stable state of homeostasis. An aberration of homeostasis leads to the development of an injury or a pathological state in various organs. DM reduces the ability of an individual to regulate the level of glucose in the bloodstream resulting in several major and some minor complications.
It is critical to appreciate that DM is a broad term used for a group of diseases that result in prolonged hyperglycemia. The mechanisms of DM are distinct and different types of DM constitute the basis of their classification.
Type 1 DM is due to an absolute lack of insulin and has an autoimmune basis. This disease was formerly named insulin-dependent diabetes mellitus (IDDM) until the reclassification of DM based on etiopathology. Immune-mediated destruction of b cells is the hallmark of the disorder, and hyperglycemia only ensues when 90% of b cells are lost.
The deficiency of insulin in synthesis and secretion is a characteristic of type 2 DM. Subsequently, that will develop insulin resistance. It is commonly diagnosed after the fourth decade of life and accounts for approximately 90% of all diabetes all over the world. As patients get older, the prevalence and incidence are on the increase. Type 2 DM is divided into two subgroups, diabetes with obesity and without obesity. Obese type 2 DM patients usually resist endogenous insulin due to alterations in cell receptors, which are associated with abdominal fat distribution. In non-obese type 2 DM, there is some insulin resistance at the post-receptor levels in addition to a deficiency in insulin production and release.
Gestational DM (GDM) refers to the occurrence of diabetes during pregnancy and its consequent resolution at the end of the gestational period. During pregnancy and the gestational period, females go through a great deal of glucose fluctuation and often experience accelerated starvation. This coupled with an increase in insulin secretion by the placenta and a decrease in insulin sensitivity by the end of the first trimester results in a transient state of insulin resistance.
Maturity Onset Diabetes of the Young (MODY) is a monogenic type of diabetes. It represents a very small percentage of patients with diabetes and is commonly diagnosed by the second decade of the patient's life. The development of the six forms of MODY is linked with mutations in several genes including hepatocyte nuclear factor 4α (HNF-4α), glucokinase gene (MODY 2) HNF-Iα, insulin promoter factor-1 (lPF-1), HNF-1β and NEUROD1. The most common mutation is in the HNF-1 α gene. This mutation accounts for nearly 70% of all MODY patients. MODY 2 and MODY 3 are the most common forms of the disease, where MODY 3 is characterized by major defects in insulin secretion. Although infrequent, it is important to establish the right diagnosis for MODY and determine the cause of diabetes to provide the most appropriate treatment.
The global prevalence of diabetes in adults according to a report published in 2013 by the IDF was 8.3% (382 million people), with 14 million more men than women (198 million men vs 184 million women), the majority between the ages 40 and 59 years. With 175 million cases still undiagnosed, the number of people currently suffering from diabetes exceeds half a billion. An additional 21 million women are diagnosed with hyperglycemia during pregnancy. The Middle East and North Africa region have the highest prevalence of diabetes (10.9%), however, the Western Pacific region has the highest number of adults diagnosed with diabetes (138.2 million) and has also countries with the highest prevalence (Fig.1). Low- and middle-income countries encompass 80% of the cases, "where the epidemic is gathering pace at alarming rates".
Fig.1 Comparative prevalence of diabetes in adults in countries with high prevalence. (Kharroubi & Darwish, 2015)
Diabetes is emerging as a major global health problem with the number of people living with diabetes expected to rise to 380 million by 2025. Approximately 10% of this population will have type 1 DM characterized by the progressive loss of β cells and complete insulin deficiency. The remaining 90% of the population will have type 2 DM characterized by insulin resistance and impaired insulin secretion. Although current management and treatment strategies can help patients with diabetes, new efficient treatments are needed.
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