Pathophysiology of Diabetes
Diabetes mellitus is a group of metabolic diseases characterized by high blood glucose levels that result from defects in insulin secretion or insulin action (Hammer & McPhee, 2019). There are two main types of diabetes – type 1 diabetes and type 2 diabetes. Both involve impaired regulation of blood glucose levels, though the underlying causes differ.
Type 1 diabetes, formerly called juvenile diabetes or insulin-dependent diabetes, is caused by an autoimmune destruction of the insulin-producing beta cells in the pancreas (Huether & McCance, 2017). Without insulin, glucose cannot enter most body cells and is instead found in high levels in the blood. Type 1 diabetes makes up approximately 5-10% of all diagnosed cases of diabetes.
Type 2 diabetes, which accounts for around 90% of diabetes cases, involves both insulin resistance – where the body’s cells ignore insulin’s signals – and an inability of the pancreatic beta cells to produce enough insulin to overcome the resistance (De Rosa et al., 2018). Genetic factors play an important role, as certain genes like TCF7L2 and SLC30A8 are linked to increased risk of developing type 2 diabetes (Dupuis et al., 2010). Obesity and physical inactivity are major lifestyle risk factors.
The pathophysiology of both types of diabetes involves impaired insulin secretion and peripheral insulin resistance. Insulin resistance means that muscle cells, liver cells, and fat cells are less responsive to insulin’s effects and have difficulty absorbing glucose from the bloodstream (De Rosa et al., 2018). This leads to elevated blood glucose levels. Over time, the pancreatic beta cells can become exhausted and fail to produce enough insulin to compensate for the insulin resistance.
Chronic hyperglycemia, or high blood sugar, can damage various organs and tissues throughout the body. Diabetes is the leading cause of new cases of blindness among adults aged 20-74 years in the United States, accounting for approximately 28% of new cases of blindness (Cheng et al., 2016). It is also a major risk factor for cardiovascular disease, stroke, kidney disease, and lower limb amputations due to reduced blood flow. Tight glycemic control has been shown to reduce the risk and progression of many diabetes complications.
Treatment for diabetes involves lifestyle modifications like diet, exercise, weight control, and medication to lower blood glucose levels. For type 1 diabetes, insulin therapy is required. Newer drug classes for type 2 diabetes like sodium-glucose transporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists work by different mechanisms to improve glycemic control and reduce cardiovascular risk factors (Davies et al., 2018). Strict management of blood sugar, blood pressure, and cholesterol levels is important to prevent or delay diabetes-related health issues.
In summary, diabetes arises from defects in insulin production or insulin action, leading to hyperglycemia. Understanding the pathophysiology provides insight into treatment and management approaches to minimize health complications from this prevalent metabolic disease. Ongoing research continues to uncover new genetic and molecular underpinnings of diabetes pathogenesis.
Cheng, Y. J., Imperatore, G., Geiss, L. S., Wang, J., Zhao, Y., Saydah, S. H., … Gregg, E. W. (2016). Secular changes in the age-specific prevalence of diabetes among U.S. adults: 1988-2010. Diabetes care, 39(11), 2119–2126.
Davies, M. J., D’Alessio, D. A., Fradkin, J., Kernan, W. N., Mathieu, C., Mingrone, G., … Buse, J. B. (2018). Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care, 41(12), 2669–2701.
De Rosa, S., Arcidiacono, B., Chiefari, E., Brunetti, A., Indolfi, C., & Foti, D. P. (2018). Type 2 diabetes mellitus and cardiovascular disease: genetic and epigenetic links. Frontiers in Endocrinology, 9, 2.
Dupuis, J., Langenberg, C., Prokopenko, I., Saxena, R., Soranzo, N., Jackson, A. U., … Florez, J. C. (2010). New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nature genetics, 42(2), 105–116.
Hammer, G. D., & McPhee, S. J. (2019). Pathophysiology of disease: An introduction to clinical medicine (8th ed.). New York, NY: McGraw-Hill Education.
Huether, S. E., & McCance, K. L. (2017). Understanding pathophysiology (6th ed.). St. Louis, MO: Mosby.

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