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Posted: October 1st, 2022

How does the pathophysiology of diabetes mellitus type 2 differ from type 1 diabetes

How does the pathophysiology of diabetes mellitus type 2 differ from type 1 diabetes, and what are the key metabolic abnormalities associated with each condition?
The pathophysiology of diabetes mellitus type 2 (T2DM) differs from type 1 diabetes (T1DM) in several aspects. T1DM is caused by an autoimmune destruction of the pancreatic beta cells, which produce and secrete insulin, resulting in absolute insulin deficiency and dependence on exogenous insulin for survival. T2DM, on the other hand, is caused by a combination of two primary factors: defective insulin secretion by pancreatic beta cells and the inability of insulin-sensitive tissues to respond appropriately to insulin, also known as insulin resistance .

Insulin resistance is the main characteristic of T2DM, and it affects mainly the liver, skeletal muscles, and adipose tissue. These tissues normally use insulin to facilitate the uptake and utilization of glucose from the bloodstream. However, in T2DM, they become less responsive to the action of insulin, leading to impaired glucose metabolism and increased glucose production by the liver. This results in hyperglycemia, or elevated blood glucose levels, which is the hallmark of T2DM .

The pancreatic beta cells, which are responsible for producing and releasing insulin in response to glucose levels, also dysfunction in T2DM. Initially, they compensate for the insulin resistance by increasing their insulin output. However, over time, this compensatory mechanism fails due to various factors, such as genetic predisposition, environmental factors, lifestyle choices, oxidative stress, inflammation, and glucotoxicity. Glucotoxicity refers to the deleterious effects of chronic hyperglycemia on the beta cells, which impair their function and survival. When the beta cells fail, endogenous insulin production declines or ceases, and exogenous insulin may be required to control blood glucose levels .

The key metabolic abnormalities associated with T1DM and T2DM are summarized in Table 1.

| Condition | Insulin secretion | Insulin sensitivity | Blood glucose levels |
| T1DM | Absent or very low | Normal or slightly reduced | High |
| T2DM | Reduced or inadequate | Reduced or impaired | High |

Table 1: Comparison of metabolic abnormalities in T1DM and T2DM.


: Westman EC. Type 2 Diabetes Mellitus: A Pathophysiologic Perspective. Front Nutr. 2021;8:707371. doi:10.3389/fnut.2021.707371
: Pathophysiology | Diabetes Mellitus Type 2 – U.OSU [Internet]. [cited 2023 Oct 5]. Available from: https://u.osu.edu/diabetestype2/diagnosis/
: Pathophysiology and Clinical Manifestations | Type 2 diabetes mellitus case study [Internet]. [cited 2023 Oct 5]. Available from: https://u.osu.edu/diabetestype2casestudy/pathophysiology/
: Kim JH, Kim HJ. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci. 2020;21(17):6275. doi:10.3390/ijms21176275

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