What are the causes of type 2 diabetes mellitus (T2DM)?

From the Guidelines

Type 2 diabetes is primarily caused by a combination of insulin resistance and insufficient insulin production, with the most significant risk factors being obesity, physical inactivity, and genetic predisposition. The main causes of type 2 diabetes can be broken down into several key factors, including:

• Obesity, particularly excess abdominal fat, which leads to inflammation and interferes with insulin function 1
• Physical inactivity, which reduces glucose uptake by muscles and worsens insulin sensitivity 1
• Genetic predisposition, with family history increasing risk by 2-6 times 1
• Age, with risk rising after 45 years 1
• Certain ethnic groups, including African Americans, Hispanics, Native Americans, and Asian Americans, face higher risk 1
• Poor diet, especially one high in processed carbohydrates, sugars, and unhealthy fats, contributes significantly 1
• Other causes include gestational diabetes history, polycystic ovary syndrome, high blood pressure, abnormal cholesterol levels, and certain medications like corticosteroids 1
• Chronic stress and sleep problems may also contribute by affecting hormone regulation 1

Understanding these causes is crucial for prevention through lifestyle modifications, including:

• Weight management 1
• Regular exercise 1
• Healthy eating 1
• Regular medical check-ups 1

It is essential to note that type 2 diabetes frequently goes undiagnosed for many years, because hyperglycemia develops gradually and, at earlier stages, is often not severe enough for the individual to notice the classic diabetes symptoms caused by hyperglycemia, such as dehydration or unintentional weight loss 1. However, even undiagnosed people with diabetes are at increased risk of developing macrovascular and microvascular complications, making early detection and prevention critical 1.

From the Research

Causes of Type 2 Diabetes

• Type 2 diabetes is caused by the complex interplay of both genetic and environmental factors 2, 3, 4, 5
• Unhealthy lifestyle, such as obesity, physical inactivity, and poor diet, are significant drivers of the epidemic of type 2 diabetes 2, 3, 4
• Genetic predisposition also plays a role in the etiology of type 2 diabetes, with multiple genetic loci associated with the disease 3
• Environmental and lifestyle changes, such as diet quality and quantity, physical activity, sleep, and socioeconomic status, contribute to diabetes risk 4
• The ultimate cause of developing overt type 2 diabetes is the loss of β-cell function, which can be influenced by genetic and environmental factors 4, 5

Risk Factors

• Obesity is a major risk factor for type 2 diabetes, and lifestyle modification is effective in obesity and type 2 diabetes prevention 3, 4
• Physical inactivity and poor diet are also significant risk factors for type 2 diabetes 2, 3, 4
• Aging, noise, fine dust, smoking, stress, and depression are additional risk factors for type 2 diabetes 4, 5
• Low socioeconomic status is also a risk factor for type 2 diabetes 4

Pathophysiology

• Hyperglycemia is the main metabolic feature of type 2 diabetes, resulting from insulin resistance and β-cell dysfunction 6, 5
• Oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and inflammation are closely correlated with insulin resistance and β-cell dysfunction 5
• The overproduction of reactive oxygen species and reduced antioxidant response are essential mechanisms underlying the pathophysiology of type 2 diabetes 5