2.16
Diabetes tipo 2 II: Fisiopatologia
Fisiopatologia
O diabetes mellitus tipo 2 (DM2) é um distúrbio metabólico crônico caracterizado por resistência à insulina e disfunção progressiva das…
O diabetes mellitus tipo 2 é um distúrbio metabólico progressivo crônico caracterizado por resistência à insulina e disfunção progressiva das células beta do pâncreas, levando a uma deteriorada regulação da glicose.
A resistência à insulina se desenvolve inicialmente no músculo esquelético, fígado e tecido adiposo.
O músculo esquelético, o principal local de absorção pós-prandial de glicose, torna-se menos responsivo à insulina, reduzindo a eliminação da glicose.
Enquanto isso, a resistência hepática à insulina resulta na produção contínua de glicose mesmo após as refeições.
Sinalização de insulina prejudicada e células alfa desreguladas elevam os níveis de glucagon, aumentando ainda mais a produção hepática de glicose.
Em resposta, as células beta inicialmente compensam aumentando a secreção de insulina; no entanto, a exposição prolongada à hiperglicemia e ao estresse metabólico prejudica progressivamente a função das células beta.
No tecido adiposo, a resistência à insulina aumenta a lipólise, elevando os ácidos graxos livres circulantes, que pioram a resistência à insulina por meio de efeitos lipotóxicos.
Essas perturbações metabólicas interconectadas sustentam coletivamente a hiperglicemia crônica.
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Q1: What causes insulin resistance in type 2 diabetes?
Insulin resistance develops initially in skeletal muscle, liver, and adipose tissue. Skeletal muscle becomes less responsive to insulin, reducing glucose clearance despite normal or high insulin levels. The liver fails to suppress gluconeogenesis, causing excess glucose production. In adipose tissue, insulin resistance increases lipolysis, elevating free fatty acids that worsen insulin resistance through lipotoxic effects.
Q2: How does hepatic glucose output increase in type 2 diabetes?
Hepatic insulin resistance prevents the liver from suppressing glucose production after meals. Additionally, impaired insulin signaling and dysregulated alpha cells elevate glucagon levels, further increasing hepatic glucose output. This dual mechanism sustains chronic hyperglycemia by maintaining elevated fasting and postprandial glucose levels despite the body's attempt to regulate blood sugar.
Q3: What happens to pancreatic beta cells over time in type 2 diabetes?
Beta cells initially compensate for insulin resistance by increasing insulin secretion. However, prolonged exposure to hyperglycemia and metabolic stress progressively impairs beta-cell function. Glucotoxicity, lipotoxicity, oxidative stress, and inflammation reduce beta-cell mass through apoptosis, leading to inadequate insulin secretion and worsening glucose control.
Q4: How do free fatty acids contribute to type 2 diabetes progression?
Elevated free fatty acids from increased adipose tissue lipolysis worsen hepatic insulin resistance and directly damage beta cells through lipotoxic effects. Reduced lipoprotein lipase activity contributes to diabetic dyslipidemia, characterized by high triglycerides, low HDL, and small dense LDL particles, further perpetuating metabolic dysfunction.
Q5: What role does skeletal muscle play in glucose regulation in type 2 diabetes?
Skeletal muscle is the primary site of postprandial glucose uptake. In type 2 diabetes, muscle insulin resistance reduces glucose clearance despite normal or elevated insulin levels. Additionally, muscle insulin resistance alters protein metabolism, increasing amino acid release that fuels gluconeogenesis, further elevating blood glucose.
Q6: How can type 2 diabetes lead to serious acute complications?
Stress hormones including cortisol and catecholamines worsen hyperglycemia and may trigger hyperosmolar hyperglycemic state or, rarely, diabetic ketoacidosis. Chronic hyperglycemia causes protein glycation, oxidative stress, and inflammation, leading to macrovascular complications such as coronary artery disease and stroke, as well as microvascular complications.
Q7: What are the long-term microvascular complications of type 2 diabetes?
Chronic hyperglycemia causes microvascular complications including diabetic neuropathy, diabetic nephropathy, and diabetic retinopathy. These result from protein glycation, oxidative stress, and inflammation affecting small blood vessels and nerves. Understanding these complications is essential for recognizing clinical manifestations and diagnosis in affected patients.