What is the primary pathophysiological defect in Type 1 diabetes mellitus (T1DM), and how does it manifest clinically without treatment?

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Answer

Decreased β-cell mass due to aging; typically presents with obesity and normal insulin levels.

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Environmental toxins triggering α-cell hyperactivity lead to chronic hypoglycemia.

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Insulin resistance in peripheral tissues leads to mild hyperglycemia without ketosis.

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Genetic defects in GLUT-4 transporters cause gestational hyperglycemia during pregnancy.

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Autoimmune destruction of β-cells causing absolute insulin deficiency; results in polydipsia, polyphagia, polyuria, weight loss, and ketoacidosis.

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