Choose A Health Problem In The Human Population ✓ Solved

Choose a health problem in the human population (examples: c

Choose a health problem in the human population (examples: cardiovascular disease, diabetes, organ-specific cancer, infectious disease). Describe the biological and physiological aspects of the health problem and potential chemical treatments or affected pathways. Discuss the natural progression (natural history) of chronic, infectious, or exposure-related illnesses. Describe potential outcomes (recovery or death) and factors leading to those outcomes. The paper should be at least 975 words and include a list of references in APA format.

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Type 2 Diabetes Mellitus: Biology, Physiology, Treatments, and Natural History

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia resulting from a combination of peripheral insulin resistance and pancreatic beta-cell dysfunction (American Diabetes Association, 2023). It is a major global public health problem associated with microvascular and macrovascular complications that raise morbidity and mortality (International Diabetes Federation, 2021; CDC, 2023).

Biological and Physiological Aspects

At the core of T2DM are two interrelated pathophysiological defects: diminished insulin sensitivity in muscle, adipose tissue, and liver, and progressive beta-cell failure. Insulin resistance impairs glucose uptake in skeletal muscle and adipose tissue and fails to suppress hepatic gluconeogenesis, leading to fasting and postprandial hyperglycemia (DeFronzo, 2009; Samuel & Shulman, 2012). Mechanistically, defects in insulin signaling pathways—especially at the insulin receptor substrate (IRS)-PI3K-Akt axis—reduce GLUT4 translocation and glucose uptake (Samuel & Shulman, 2012).

Beta-cell dysfunction evolves from genetic predisposition, chronic metabolic stress (glucotoxicity), lipid-induced toxicity (lipotoxicity), and inflammatory mediators from adipose tissue. Over time, insulin secretory capacity declines, reducing the ability to compensate for insulin resistance and precipitating hyperglycemia (DeFronzo, 2009; ADA, 2023).

Other physiological contributors include dysregulated incretin hormones (GLP-1, GIP), altered hepatic lipid metabolism, and renal glucose handling via sodium-glucose cotransporter 2 (SGLT2). These pathways collectively determine glycemic homeostasis and represent therapeutic targets (Rena, Hardie, & Pearson, 2017).

Chemical Treatments and Affected Pathways

T2DM pharmacotherapy targets multiple biochemical pathways to lower glucose and reduce complications. Metformin, a first-line agent, primarily reduces hepatic gluconeogenesis and enhances insulin sensitivity partly via activation of AMP-activated protein kinase (AMPK) and modulation of mitochondrial respiration (Rena et al., 2017). Sulfonylureas stimulate insulin secretion by closing pancreatic beta-cell KATP channels, acting downstream of glucose sensing (ADA, 2023).

Thiazolidinediones (e.g., pioglitazone) act as PPARγ agonists to enhance adipocyte insulin sensitivity and adipose lipid storage, reducing ectopic lipid accumulation (DeFronzo, 2009). Dipeptidyl peptidase-4 (DPP-4) inhibitors and GLP-1 receptor agonists augment incretin signaling, promoting glucose-dependent insulin secretion and, for GLP-1 agonists, weight loss and cardiovascular benefits (ADA, 2023).

SGLT2 inhibitors block renal glucose reabsorption in the proximal tubule, reducing plasma glucose and providing cardiovascular and renal protection independent of glycemic effects (Zinman et al., 2015). Insulin therapy substitutes endogenous insulin when beta-cell failure is advanced. Each class impacts distinct molecular targets—AMPK, PPARγ, GLP-1 receptor, SGLT2, or beta-cell ion channels—offering complementary mechanisms to manage hyperglycemia and disease progression.

Natural Progression and Natural History

T2DM typically progresses from a prolonged prediabetic state characterized by impaired fasting glucose or impaired glucose tolerance due to worsening insulin resistance and compensatory hyperinsulinemia. As beta-cell compensatory capacity fails, fasting and postprandial glucose rise and overt diabetes develops (ADA, 2023).

Without effective management, chronic hyperglycemia drives microvascular complications—retinopathy, nephropathy, and neuropathy—through mechanisms such as advanced glycation end-product formation, oxidative stress, and inflammation (Forbes & Cooper, 2013). Macrovascular disease (atherosclerotic cardiovascular disease) is accelerated by dyslipidemia, hypertension, and pro-inflammatory states common in T2DM, and remains the leading cause of mortality (CDC, 2023).

Longitudinal studies, notably the UK Prospective Diabetes Study (UKPDS), demonstrate that early and intensive glycemic and risk-factor control reduce the incidence of complications; however, the “legacy effect” shows that early hyperglycemia can have long-lasting adverse consequences (UKPDS Group, 1998). Thus, natural history includes progressive decline in beta-cell function, increasing medication requirements, and rising risk of organ-specific complications over years to decades.

Potential Outcomes and Determinants

Outcomes range from maintained health with controlled glycemia to severe disability or death from vascular complications. Recovery in the sense of permanent normalization of glucose metabolism is uncommon for long-standing disease, but remission (sustained normoglycemia without pharmacotherapy) can occur following substantial weight loss, bariatric surgery, or intensive lifestyle interventions, particularly in early disease (ADA, 2023; IDF, 2021).

Conversely, mortality risk increases with poor glycemic control, longer disease duration, presence of cardiovascular disease, chronic kidney disease, and comorbidities such as obesity and smoking (CDC, 2023). Pharmacologic advances—SGLT2 inhibitors and GLP-1 receptor agonists—have reduced cardiovascular and renal event rates in randomized controlled trials, improving survival for many patients (Zinman et al., 2015; ADA, 2023).

Socioeconomic factors, access to care, adherence to therapies, and timely diagnosis also materially affect outcomes. Early detection and multidimensional management of glycemia, blood pressure, lipids, and lifestyle reduce the risk of complications and mortality (UKPDS Group, 1998; ADA, 2023).

Summary

Type 2 diabetes is a complex metabolic disorder driven by insulin resistance and progressive beta-cell dysfunction. Treatment targets multiple biochemical pathways—AMPK, insulin signaling, incretin axes, PPARγ, and renal glucose transporters—to improve glycemic control and reduce complications. The disease naturally progresses from prediabetes to overt diabetes and, without effective intervention, to disabling and life-threatening vascular complications. Outcomes depend on early detection, comprehensive management, individual biology, and social determinants of health; while remission is possible in some, prevention and control remain the most reliable means to reduce mortality and morbidity (DeFronzo, 2009; ADA, 2023).

References

  • American Diabetes Association. (2023). Classification and diagnosis of diabetes: Standards of medical care in diabetes—2023. Diabetes Care, 46(Supplement_1), S19–S40.
  • Centers for Disease Control and Prevention. (2023). National Diabetes Statistics Report, 2023. U.S. Department of Health and Human Services. https://www.cdc.gov/diabetes/data/statistics-report/index.html
  • DeFronzo, R. A. (2009). From the triumvirate to the ominous octet: A new paradigm for the treatment of type 2 diabetes mellitus. Diabetes, 58(4), 773–795.
  • Forbes, J. M., & Cooper, M. E. (2013). Mechanisms of diabetic complications. Physiological Reviews, 93(1), 137–188.
  • International Diabetes Federation. (2021). IDF Diabetes Atlas (10th ed.). https://www.diabetesatlas.org
  • National Institute of Diabetes and Digestive and Kidney Diseases. (2022). Diabetes Overview. https://www.niddk.nih.gov/health-information/diabetes
  • Rena, G., Hardie, D. G., & Pearson, E. R. (2017). The mechanisms of action of metformin. Diabetologia, 60(9), 1577–1585.
  • Samuel, V. T., & Shulman, G. I. (2012). Mechanisms for insulin resistance: Common threads and missing links. Cell, 148(5), 852–871.
  • UK Prospective Diabetes Study (UKPDS) Group. (1998). Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in type 2 diabetes. The Lancet, 352(9131), 837–853.
  • Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., ... & EMPA-REG OUTCOME Investigators. (2015). Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. New England Journal of Medicine, 373(22), 2117–2128.

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