TYPE 2 DIABETES

 

Diabetes mellitus (DM) is a chronic disease characterised by persistent hyperglycaemia (raised blood sugar levels), resulting from defective insulin secretion, resistance to insulin, or both (1). Both are required to be present before being diagnosed with type 2 DM (T2DM) (2). Yet, while insulin resistance is entirely evident from the pre-diabetic stage, defective insulin secretion develops over time, aligned with a gradual decline in both beta cell (insulin secreting cell) function. Insulin is a hormone that signals the uptake of glucose into the body’s cells and inhibits glucose production from the liver, thus plays a key role in the regulation of blood glucose levels (3).

Hyperglycaemia if left untreated, will lead to the long-term damage of numerous bodily systems, in particular the nerves and blood vessels, resulting in the development of potentially serious health implications, most notably microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular complications leading to a 2-fold to a 4-fold increased risk of cardiovascular diseases (4).

Type 2 Diabetes Mellitus

Type 2 diabetes is the most common type of diabetes, accounting for up to around 90% of all cases (5). T2DM largely results from the interaction among genetic, environmental, and behavioural risk factors (6). Many who develop T2DM are genetically predisposed, however T2DM is largely related to obesity or excess body fat, mainly distributed in the mid-section (2). T2DM is most common in adults (> 45 years), however, is now more frequently being seen in young adults, adolescents, and even children, which can be attributed to rising levels of obesity, physical inactivity, and energy-dense diets (7).

Pathophysiology

The primary pathophysiological factor of T2DM is insulin resistance, and essentially this is when the body tissues, primarily muscle and liver, have an insensitivity to insulin, in other words the ability for insulin to stimulate uptake of glucose into cells is impaired (8). However, initially, there is an increase in insulin production to compensate in order to maintain near normal blood glucose levels, but after a while, in the presence of defective beta cell function, insulin production begins to decline and hyperglycaemia is the end result (9).

Symptoms

If not treated, blood glucose levels remain chronically elevated. However, T2DM often presents with no symptoms initially, thus as a result can go undiagnosed for a number of years following onset, and by then complications have generally entered into the frame (4). However, like type 1 DM, the most common symptoms include increased thirst, frequent urination, lethargy, delayed wound healing, and sometimes blurred vision (10).

Prevention and Treatment

Since T2DM is strongly associated with overweight or obesity and insulin resistance, weight loss and maintaining a normal body weight is the primary target of its clinical management (11). Reduction in body weight is also associated with improvements in glycaemia, blood pressure, and lipid profile and hence can delay or prevent complications, especially incidence of cardiovascular events (12).

Simple lifestyle measures including diet modification (calorie restriction) to reduce energy intake, and regular exercise (at least 30 minutes, moderate-intensity five days per week) to increase energy expenditure, have been shown to be effective in the prevention or delayed onset of T2DM (13, 14). In people at an increased risk of developing T2DM, prevention of the disease through lifestyle modification isn’t a given, however can help delay the onset of diabetes for several years (15).

Type 2 diabetes is traditionally treated in a stepwise manner. Initial therapy is usually diet and increased exercise to promote weight loss (16, 17, 18). This weight reduction may improve insulin sensitivity, and in turn result in better regulation of blood glucose (19). However, for the majority, lifestyle measures generally fail to completely control glycaemia and, therefore, pharmacological treatment is instigated (20).

Initial therapy is with a single oral drug, usually Metformin (inhibits glucose production in the liver), and Sulfonylureas are generally the second-line therapy in T2DM patients, however, can be used in place of metformin if the patient is not overweight, or cannot tolerate metformin (21). Monotherapy often fails over a period of time and a combination of two or more oral therapies is used (22). Eventually, failure of all oral combination therapy may occur when β-cell failure has progressed to such a degree that additional, exogenous insulin is then required (21).

References

Maitra. A, and Abbas, A.K. (2005). Robbins and Cotran Pathologic basis of disease: Endocrine system. (7th edn). Philadelphia, Saunders.

Olokoba, A., Obateru, O. and Olokoba, L. (2012) "Type 2 Diabetes Mellitus: A Review of Current Trends", Oman Medical Journal, 27(4), pp. 269-273. doi: 10.5001/omj.2012.68.

Del Prato, S., Bianchi, C., Miccoli, R. and Penno, G. (2007). Pharmacological intervention in prediabetes: considering the risks and benefits. Diabetes, Obesity and Metabolism, 9(s1), pp.17-22.

World Health Organization (2018) Diabetes, Who.int. Available at: https://www.who.int/news-room/fact-sheets/detail/diabetes.

Tripathi, B.K. and Srivastava A.K. (2006). “Diabetes mellitus: complications and therapeutics”. Medical Science Monitor, 12(7):RA130–147.

Chen, L., Magliano, D. and Zimmet, P. (2011) "The worldwide epidemiology of type 2 diabetes mellitus—present and future perspectives", Nature Reviews Endocrinology, 8(4), pp. 228-236. doi: 10.1038/nrendo.2011.183.

Weigensberg, M. and Goran, M. (2009) "Type 2 diabetes in children and adolescents", The Lancet, 373(9677), pp. 1743-1744. doi: 10.1016/s0140-6736(09)60961-2.

Goyal, R. and Jialal, I. (2018) Diabetes Mellitus Type 2, Ncbi.nlm.nih.gov. Available at: https://www.ncbi.nlm.nih.gov/books/NBK513253/.

DeFronzo, R. (2004) "Pathogenesis of type 2 diabetes mellitus", Medical Clinics of North America, 88(4), pp. 787-835. doi: 10.1016/j.mcna.2004.04.013.

American Diabetes Association (2010) "Diagnosis and Classification of Diabetes Mellitus", Diabetes Care, 33(Supplement_1), pp. S62-S69. doi: 10.2337/dc10-s062.

Ley, S. et al. (2014) "Prevention and management of type 2 diabetes: dietary components and nutritional strategies", The Lancet, 383(9933), pp. 1999-2007. doi: 10.1016/s0140-6736(14)60613-9.

Forouhi, N. et al. (2018) "Dietary and nutritional approaches for prevention and management of type 2 diabetes", BMJ, p. k2234. doi: 10.1136/bmj.k2234.

Li, G. et al. (2014) "Cardiovascular mortality, all-cause mortality, and diabetes incidence after lifestyle intervention for people with impaired glucose tolerance in the Da Qing Diabetes Prevention Study: a 23-year follow-up study", The Lancet Diabetes & Endocrinology, 2(6), pp. 474-480. doi: 10.1016/s2213-8587(14)70057-9.

Knowler, W.C., Fowler, S.E., Hamman, R.F., Christophi C.A., Hoffman, H.J., Brenneman, A.T. et al., (2009). "10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study" The Lancet, (9702), pp. 1677-1686. doi: 10.1016/s0140-6736(09)61457-4.

American Diabetes Association (2015). "Prevention or Delay of Type 2 Diabetes". Diabetes Care. (Supplement 1), pp. S36-S38. doi: 10.2337/dc16-s007.

Lai, L. et al. (2018) "Screening for non‐alcoholic fatty liver disease in patients with type 2 diabetes mellitus using transient elastography", Journal of Gastroenterology and Hepatology. doi: 10.1111/jgh.14577.

Eckstein, M. et al. (2018) "Physical exercise and non‐insulin glucose‐lowering therapies in the management of Type 2 diabetes mellitus: a clinical review", Diabetic Medicine. doi: 10.1111/dme.13865.

Massey, C. et al. (2018) "Well-being interventions for individuals with diabetes: A systematic review", Diabetes Research and Clinical Practice, 147, pp. 118-133. doi: 10.1016/j.diabres.2018.11.014.

Escalante-Pulido, M., Escalante-Herrera, A., Milke-Najar, M.E. and Alpizar-Salazar, M. (2003). “Effects of weight loss on insulin secretion and in vivo insulin sensitivity in obese diabetic and non-diabetic subjects”. Diabetes, nutrition, and metabolism. 16(5-6):277-83.

Masuo, K. (2013) "Lifestyle Modification Is the First Line Treatment for Type 2 Diabetes", Type 2 Diabetes. doi: 10.5772/56377.

Packer, M. (2015) "Type 2 diabetes: pharmacological management strategies", The Pharmaceutical Journal. doi: 10.1211/pj.2015.20069631.

Chamberlain, J. et al. (2017) "Pharmacologic Therapy for Type 2 Diabetes: Synopsis of the 2017 American Diabetes Association Standards of Medical Care in Diabetes", Annals of Internal Medicine, 166(8), p. 572. doi: 10.7326/m16-2937.

RELATED ARTICLES

Nutrition and Disease

Type 1 Diabetes

  Pathophysiology  Type 1 diabetes mellitus is the destruction of insulin-secreting beta-cells,...

Jonple
Jonple