Type 2 Diabetes: Pathophysiology, Genetics, and Treatment

Introduction to Type 2 Diabetes Pathophysiology

The pathophysiology of Type 2 diabetes is rooted in the body's dysfunctional relationship with insulin. Either the body produces too little insulin to meet its own needs, or the body develops a resistance to the insulin it does produce — meaning that even if sufficient insulin is present, cells fail to respond to it. The cause involves "a combination of genetic factors related to impaired insulin secretion and insulin resistance" compounded by external influences "such as obesity," inadequate exercise, and aging (Kaku, 2010, p. 41).

Age Continuum and Diagnosis Risk

Wilmot and Idris (2014) demonstrate that there is an age continuum of risk associated with Type 2 diabetes, and they challenge the practice of dividing diagnosis onset into just two discrete categories — pediatric (under 20 years of age) and adult (over 20). They argue that such a division serves only a practical or administrative purpose and does nothing to address the development of Type 2 diabetes in later or elderly populations. This oversight is important for several reasons. First, it fails to account for the fact that Type 2 diabetes in patients under 45 is associated with a tenfold increased rate of developing myocardial infarction (Wilmot & Idris, 2014, p. 235). Second, around the age of 45, women may still bear children, and if they have Type 2 diabetes, specific preparations and medical considerations are required. A generic diagnostic cutoff between pediatric and adult is therefore inadequate for adults who must manage the disease across many different developmental stages over a considerably longer duration.

Genetic Factors and Genome-Wide Research

The genomic dimensions of Type 2 diabetes point toward "novel pathways" in fundamental biology, including the "role of β-cell dysfunction" (Billings & Florez, 2010, p. 59). The precise genetic heritability of the disease remains unclear. Although causal genomic regions have been identified through genome-wide association studies, these are located primarily in the region of the β-cell. Nevertheless, there is little direct evidence of causality between the gene denoting that region and the actual onset of disease (Billings & Florez, 2010).

As Billings and Florez (2010) note, genome-wide mapping has identified "38 SNPs associated with T2D" and more than 24 SNPs bearing some relation to "glycemic traits," yet the causal variant remains elusive (p. 60). While these genetic explorations are informative, they have not isolated a single identifiable causative genetic agent. What is known is the region of the genomic sequence where diabetes-related variants appear; what remains unknown is how, why, or even whether this region plays a direct causative role in the disease's onset.

References

Billings, L., & Florez, J. (2010). The genetics of type 2 diabetes: what have we learned from GWAS? Annals of the New York Academy of Sciences, 1212, 59–77.

Cunningham-Myrie, C., Theall, K., Younger, N., et al. (2015). Associations between neighborhood effects and physical activity, obesity, and diabetes: The Jamaica Health and Lifestyle Survey, 2008. Journal of Clinical Epidemiology, 68(9), 970–978.

Davis, B. (2012). Defeating diabetes: Lessons from the Marshall Islands. Today's Dietitian, 10(8), 24.

Holmer, K., Ogden, L., Burda, B., & Norris, S. (2013). Quality of clinical practice guidelines for glycemic control in Type 2 diabetes mellitus. PLoS One, 8(4), e58625.

International Diabetes Federation. (2012). Global guideline for Type 2 diabetes. IDF Clinical Guidelines Task Force.

Kaku, K. (2010). Pathophysiology of Type 2 diabetes and its treatment policy. JMAJ, 53(1), 41–46.

Wilmot, E., & Idris, I. (2014). Early onset type 2 diabetes: risk factors, clinical impact and management. Therapeutic Advances in Chronic Disease, 5(6), 234–244.