Molecular and Cellular Basis of Diabetes: Types, Symptoms & Treatment

Introduction

Diabetes is a chronic lifestyle disorder that occurs when the body fails to produce enough insulin or does not use it effectively. There are several types of diabetes — type 1, type 2, gestational, and type 3 — of which type 1 and type 2 are the most common. Diabetic patients may present with a range of symptoms that differ from person to person. These symptoms should be managed properly to avoid poor clinical outcomes, some of which may be severe and long-lasting. Accordingly, the risks and symptoms of diabetes should be minimized by embracing a healthy lifestyle and adhering to relevant clinical interventions when diagnosed.

To manage diabetes effectively, it is essential to understand its underlying causes. Diabetes results when insulin is depleted after beta (β) cells are destroyed. At present, metformin is considered one of the most effective medications for the treatment of diabetes owing to its favorable safety profile. Various studies — including recent research — indicate that metformin suppresses hepatic gluconeogenesis by activating adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK). This paper explains the history, symptoms, and prognosis of diabetes, with a focus on type 1 and type 2, and examines the molecular and cellular basis of the disease as well as the mechanism of action of relevant diabetes medications.

History of Diabetes

Diabetes, also referred to as diabetes mellitus, is a disease characterized by the presence of excess sugar in the urine. The disease has roots in ancient history. The ancient Egyptian physicians were the first individuals to describe clinical features resembling diabetes, around 1500 B.C. (Ahmed, 2019). The term "diabetes" was first coined by Aretaeus the Cappadocian between 980 and 1037 A.D. Physicians in India historically referred to the condition as "honey urine" and would test for it by determining whether it attracted ants. In 1776, the presence of sugar in blood and urine was confirmed by Gibson.

Symptoms of Diabetes

The symptoms of diabetes vary depending on the elevation of blood sugar in the body. Individuals with type 3 diabetes may not show any symptoms. However, individuals with type 1 and type 2 diabetes tend to experience more pronounced symptoms (Mayo Clinic, 2020). Notably, individuals with type 2 diabetes may be asymptomatic initially, and their symptoms develop slowly compared to those of type 1 diabetes, which tend to appear more rapidly (Kharroubi and Darwish, 2015).

Diabetic patients may present with symptoms including, but not limited to: frequent infections, slow-healing sores, blurred vision, irritability, fatigue, ketones in the urine, unexplained weight loss, extreme hunger, frequent urination, and increased thirst. These symptoms also vary by age group. For instance, in adolescents and children, ketoacidosis often presents as the first symptom of type 1 diabetes (Kahanovitz et al., 2017). According to these authors, fatigue, weight loss, increased thirst, frequent urination, and increased appetite are caused by fluid losses, concurrent caloric deficits, and elevated glucose levels in the urine owing to faulty glucose transport in the body.

Diabetes Prognosis

Diabetes prognosis depends significantly on the type of diabetes. According to Goyal and Jialal (2021), type 2 diabetes increases the risk of cardiovascular disease. This risk can be reduced through smoking cessation, regular exercise, statin use, and blood pressure management. On the other hand, Elsamahy et al. (2017) indicate that type 1 diabetes tends to have poor clinical outcomes in children and females, particularly with respect to glycemic index and insulin requirements.

If diabetes is poorly managed, it may lead to coma, unconsciousness, mental confusion, cerebral edema, and even death. Beyond these acute outcomes, poorly managed diabetic symptoms may also contribute to other long-term complications. For instance, untreated diabetes may damage blood vessels, which can in turn be associated with peripheral vascular disease, stroke, and heart disease (Kahanovitz et al., 2017). Small blood vessels may also be destroyed, leading to blindness as a consequence of diabetic retinopathy.

Molecular and Cellular Basis of Diabetes

The precise molecular basis of diabetes is not yet fully understood. However, various researchers indicate that diabetes results from the depletion of insulin following the severe destruction of β cells located in the islets of Langerhans within the pancreas (Kelly et al., 2003). In type 1 diabetes, insulin depletion leads to hyperglycemia caused by autoimmunity in T cells, which results in decreased cellular uptake of glucose and increased hepatic gluconeogenesis (DiMeglio et al., 2018). Depleted insulin in the body may also lead to increased fatty acid oxidation and breakdown (Kelly et al., 2003).

In type 2 diabetes, Tamarai et al. (2019) found that insulin depletion is caused by four cellular processes: autoimmunity and inflammation, oxidative stress, glucotoxicity, and lipotoxicity. Glucotoxicity alters the cellular components involved in insulin secretion, while lipotoxicity leads to increased fatty acid accumulation in the pancreas, resulting in cellular damage. These processes impair β cells, which then leads to the overproduction of reactive oxygen species. This overproduction decreases insulin sensitivity and secretion, reduces calcium influx — resulting in apoptosis — decreases the ATP-to-ADP ratio, and increases protein kinase inhibitor activity (Tamarai et al., 2019). This vulnerability is largely attributable to the fact that β cells are particularly susceptible to oxidative stress, as they lack several key antioxidants including catalase, glutathione, and superoxide dismutase (SOD).