N4 Pathophysiology AY 23-24

Hello, Group 4!
We were thoroughly impressed by the detailed and well-organized pathophysiology diagram your group created. Great job!

Regarding our group’s collective questions about the diagram:

1. The patient has a family history of myocardial infarction, specifically the patient’s father. Given this family history, how does insulin resistance aggravate the development of T2DM for the patient?
2. Based on the diagram, does having gestational diabetes mellitus always lead to T2DM?

That's all and thank you!
Best regards, Group 2

Hello, Group 4! Here are some of the questions and comments that we would like to clarify regarding your pathophysiology diagram:

GROUP 4 - DM

1. You’ve identified obesity as a risk factor for T2DM associating it with insulin resistance. With this clear link, what accounts for the fact that some obese individuals never develop diabetes?

2. Your diagram suggests a progressive loss of β-cell function. How reversible is this once it begins?

3. If the patient is not allergic to penicillin, how do you think it would help in the patient’s treatment for T2DM?

We would also like to add a comment that the diagram was very comprehensive, and that the flow of events is organized well. We would also suggest that it would be better if the blue and violet colors were more distinct since they look somewhat similar especially when they are placed side by side.

Thank you and best of luck!

Group 1

Greetings!

The following are answers to all the questions from the different groups:

1. YOU’VE IDENTIFIED OBESITY AS A RISK FACTOR FOR T2DM ASSOCIATING IT WITH INSULIN RESISTANCE. WITH THIS CLEAR LINK, WHAT ACCOUNTS FOR THE FACT THAT SOME OBESE INDIVIDUALS NEVER DEVELOP DIABETES?
The variation in how diabetes progresses among obese individuals suggests that factors beyond obesity influence the development of type 2 diabetes mellitus (T2DM). Some obese individuals may have better insulin sensitivity and metabolic resilience due to genetic factors or healthier lifestyle habits, which reduces their risk of developing diabetes. Conversely, others may have genetic predispositions or concurrent health conditions that increase their susceptibility to insulin resistance and diabetes. These factors contribute to the variability in diabetes development among obese individuals, making T2DM a multifactorial disease.

2. YOUR DIAGRAM SUGGESTS A PROGRESSIVE LOSS OF Β-CELL FUNCTION. HOW REVERSIBLE IS THIS ONCE IT BEGINS?
β-cells initially increase insulin secretion to compensate for insulin resistance, but their function and mass decline over time, exacerbating inadequate insulin secretion. As the disease progresses, β-cells can lose their identity, dedifferentiate, and even transform into other cell types. Although treatments like incretin-based drugs can restore some β-cell function, a complete reversal of β-cell dysfunction is difficult.

3. IF THE PATIENT IS NOT ALLERGIC TO PENICILLIN, HOW DO YOU THINK IT WOULD HELP IN THE PATIENT’S TREATMENT FOR T2DM? (Answered after the presentation) 
Penicillin is an antibiotic administered when an infection is present or when there's a high risk of infection development. This medication is specifically for wound treatment and does not directly impact the management of diabetes. However, given that the client has a diabetic injury, and an open wound susceptible to infection, penicillin could potentially address this concern. It could aid in managing the infection, fostering wound healing, and averting additional complications.

4. THE PATIENT HAS A FAMILY HISTORY OF MYOCARDIAL INFARCTION, SPECIFICALLY THE PATIENT’S FATHER. HOW DOES INSULIN RESISTANCE AGGRAVATE THE DEVELOPMENT OF T2DM FOR THE PATIENT GIVEN THE FAMILY HISTORY?
Insulin resistance can lead to heart disease in several ways. First, it causes hyperglycemia, which damages the inner lining of blood vessels and makes them less flexible. It also results in (dyslipidemia) unhealthy levels of fats in the blood, such as high triglycerides and LDL (bad) cholesterol, and low HDL (good) cholesterol, which can clog arteries. Additionally, insulin resistance triggers inflammation by increasing inflammatory cytokines and decreasing anti-inflammatory ones. This inflammation further damages blood vessels and accelerates the buildup of plaques, which are fatty deposits that can block arteries. These plaques can become unstable and lead to heart attacks or strokes. Together, these effects make cardiovascular disease more likely in people with insulin resistance.

5. BASED ON THE DIAGRAM, DOES HAVING GESTATIONAL DIABETES MELLITUS ALWAYS LEAD TO T2DM? (Answered after the presentation) 
Having gestational diabetes mellitus does not always lead to type 2 diabetes mellitus. While GDM increases the risk of developing T2DM by about 10-fold higher than with a normal pregnancy in both the mother and the child, it is not an absolute result. With effective lifestyle changes after delivery, GDM can not lead to T2DM. In our patient’s case, however, there are predisposition factors that aggravate her condition, thus, evidently leading to the development of Type 2 DM.

6. IN WHAT WAY DOES INCREASED INSULIN RESISTANCE AFFECT THE EFFICACY OF THE PATIENT’S CURRENT MEDICATIONS? I NOTICED THAT THERE’S AN INCREASE IN THE DOSAGE OF GLIMEPIRIDE, IS IT CONCERNED WITH ITS EFFECTIVENESS IN THE PATIENT?
Chronic overwork can eventually cause the pancreatic beta cells to malfunction, which lowers insulin output. Metformin and glimepiride function to enhance insulin sensitivity and promote insulin production, respectively. However, in the context of insulin resistance, even increased insulin secretion may not suffice to lower blood glucose levels adequately, as the cells are less responsive to the insulin available. Also, this makes these drugs less effective since they correlate with other metabolic abnormalities such as increased hepatic glucose output and dyslipidemia. Stronger medications, like insulin, are required due to the combination of insufficient insulin action and the steady reduction in beta-cell function; yet, the patient in this circumstance is unwilling to utilize insulin.

7. WHEN (REFERRING) TO THE GRADUAL DECLINE IN Β-CELL FUNCTION DUE TO A COMBINATION OF GENETIC, METABOLIC, AND ENVIRONMENTAL FACTORS, WHAT ARE THESE SPECIFIC FACTORS?
In this case, the genetic factor involves a family history where the mother has type 2 diabetes and the father has had a myocardial infarction, suggesting a predisposition to insulin resistance. Metabolic factors include persistent high blood sugar, which disrupts the normal insulin secretion process, reduces insulin gene expression, and impairs insulin production. Additionally, fat accumulation (lipotoxicity) triggers cell death pathways in β-cells. Meanwhile, environmental factors include the client's sedentary lifestyle, a high-fat diet contributing to lipotoxicity, and obesity, which leads to the release of free fatty acids (FFAs) and pro-inflammatory cytokines that damage β-cells.

 

Additionally, here is a copy of our updated and final Pathophysiology Diagram:

 

Thank you!