Glucose Regulation and Diabetes Management

Explain the role of insulin and glucagon in glucose homeostasis., How do defects in insulin secretion and action contribute to the pathogenesis of type 2 diabetes mellitus (T2DM)?, What are the different classes of glucose-lowering medications used to treat T2DM, and how do they target various physiological pathways to improve glycemic control?, How does the pathophysiology of T2DM differ from type 1 diabetes, and what are the potential complications associated with chronic hyperglycemia including neuropathy retinopathy and nephropathy?

Insulin and glucagon play critical roles in maintaining glucose homeostasis. Insulin, secreted by pancreatic beta cells, lowers blood glucose by promoting glucose uptake in muscle and adipose tissue and suppressing hepatic glucose production. Glucagon, secreted by alpha cells, has the opposite effect, increasing blood glucose by stimulating glycogenolysis and gluconeogenesis in the liver.

Pathogenesis of Type 2 Diabetes

In type 2 diabetes mellitus (T2DM), insulin resistance and defective insulin secretion contribute to chronic hyperglycemia. Cells become less responsive to insulin, forcing the pancreas to produce more. Over time, beta cells fail, leading to progressive loss of glycemic control. Contributing factors include genetics, obesity, inflammation, and sedentary lifestyle.

Glucose-Lowering Medications

Several drug classes target different physiological pathways:

• Biguanides (Metformin) – Reduces hepatic glucose production and improves insulin sensitivity.
• Sulfonylureas & Meglitinides – Stimulate insulin secretion from pancreatic beta cells.
• Thiazolidinediones (TZDs) – Enhance insulin sensitivity in peripheral tissues.
• DPP-4 Inhibitors – Prolong the action of incretin hormones to increase insulin release.
• GLP-1 Receptor Agonists – Enhance insulin secretion and delay gastric emptying.
• SGLT2 Inhibitors – Increase urinary glucose excretion by inhibiting renal glucose reabsorption.
• Insulin Therapy – Required in advanced cases when beta-cell function is severely compromised.

Type 1 vs. Type 2 Diabetes

Unlike T1DM, an autoimmune disease leading to total beta-cell destruction, T2DM involves insulin resistance and gradual beta-cell dysfunction. T1DM requires lifelong insulin therapy, while T2DM is often managed with lifestyle modifications and oral medications before progressing to insulin dependence.

Complications of Chronic Hyperglycemia

Poorly controlled T2DM leads to:

• Neuropathy – Nerve damage causing pain, numbness, and autonomic dysfunction.
• Retinopathy – Microvascular damage leading to vision loss.
• Nephropathy – Chronic kidney disease progressing to renal failure.
• Cardiovascular Disease – Increased risk of heart attack and stroke.APA