Metabolic Integration

Metabolic Integration Indian Medical PG Question 1: Organ that can utilize glucose, fatty acids and ketone bodies is:

• A. Liver
• B. Brain
• C. Skeletal muscle (Correct Answer)
• D. RBC

Metabolic Integration Explanation: ***Skeletal muscle*** - Skeletal muscle is highly adaptable and can utilize **glucose**, **fatty acids (FAs)**, and **ketone bodies** as fuel sources, especially during prolonged exercise or starvation. - Its metabolic flexibility allows it to switch between these substrates depending on their availability and the body's energy demands. *Liver* - The liver is central to metabolism but primarily **produces ketone bodies** from fatty acids rather than utilizing them as a major fuel source for its own energy needs. - While it uses glucose and FAs, its role in ketone body metabolism is largely synthetic. *Brain* - The brain preferentially uses **glucose** as its primary fuel. - During prolonged starvation, it can adapt to utilize **ketone bodies** as an alternative fuel source, but it does not significantly use fatty acids directly. *RBC* - Red blood cells (RBCs) lack mitochondria and therefore rely exclusively on **anaerobic glycolysis** for energy, metabolizing only **glucose**. - They cannot utilize fatty acids or ketone bodies.

Metabolic Integration Indian Medical PG Question 2: Mr. Murali has 126 mg/dl of fasting plasma glucose. His venous plasma glucose 2h after ingestion of 75g oral glucose load is 149 mg/dl. This patient comes under which stage of WHO diagnostic criteria of diabetes & intermediate hyperglycemia?

• A. Decreased glucose resistance
• B. IFG - Impaired fasting glucose
• C. Diagnosis of diabetes (Correct Answer)
• D. Impaired glucose tolerance

Metabolic Integration Explanation: **Diagnosis of diabetes** - The **fasting plasma glucose (FPG)** of 126 mg/dL meets the WHO criterion for **diabetes**, which is FPG ≥ 126 mg/dL [1]. - Although the 2-hour post-glucose load (149 mg/dL) falls within the **impaired glucose tolerance (IGT)** range (140-199 mg/dL), the elevated fasting glucose alone is sufficient for a diabetes diagnosis according to WHO guidelines. *Decreased glucose resistance* - This term is not a standard diagnostic category recognized by the WHO for glucose metabolism disorders. - Glucose resistance is more commonly associated with conditions like **insulin resistance** rather than a specific diagnostic stage [1]. *IFG - Impaired fasting glucose* - **Impaired fasting glucose (IFG)** is defined by a fasting plasma glucose level between 100 mg/dL and 125 mg/dL. - Mr. Murali's fasting glucose of 126 mg/dL is higher than the upper limit for IFG [1]. *Impaired glucose tolerance* - **Impaired glucose tolerance (IGT)** is defined by a 2-hour post-glucose load plasma glucose level between 140 mg/dL and 199 mg/dL. - While Mr. Murali's 2-hour reading of 149 mg/dL falls within this range, the elevated fasting glucose level takes precedence for the overall diagnosis [1].

Metabolic Integration Indian Medical PG Question 3: Which of the following is FALSE about insulin action?

• A. Insulin promotes glycolysis
• B. Insulin promotes ketogenesis (Correct Answer)
• C. Insulin promotes glycogen synthesis
• D. Insulin promotes lipogenesis

Metabolic Integration Explanation: ***Insulin promotes ketogenesis*** - Insulin is an **anabolic hormone** that works to prevent excessive **fat breakdown** and the formation of **ketone bodies**. - High insulin levels actively **inhibit** enzymes involved in ketogenesis, such as **carnitine palmitoyltransferase-1 (CPT1)**, thereby reducing the transport of fatty acids into mitochondria for oxidation. *Insulin promotes glycolysis* - Insulin stimulates **glycolysis**, particularly in the liver and muscle, by increasing the activity of key enzymes like **glucokinase** and **phosphofructokinase-1**. - This promotes the breakdown of glucose for **energy production** and provides substrates for fat synthesis. *Insulin promotes glycogen synthesis* - Insulin is a primary regulator of **glycogen synthesis** in the liver and muscles. - It activates **glycogen synthase** and inhibits glycogen phosphorylase, thereby shunting glucose towards storage as **glycogen**. *Insulin promotes lipogenesis* - Insulin promotes **lipogenesis** (fat synthesis) in adipose tissue and liver. - It increases glucose uptake into adipocytes and stimulates enzymes like **acetyl-CoA carboxylase** and **fatty acid synthase**, converting excess carbohydrates into fatty acids and subsequently **triglycerides**.

Metabolic Integration Indian Medical PG Question 4: The appropriate statistical test to find out obesity as a significant risk factor for breast cancer is:

• A. Chi-square test (Correct Answer)
• B. Wilcoxon’s signed rank test
• C. Student’s paired ‘t’ test
• D. Student’s unpaired ‘t’ test

Metabolic Integration Explanation: ***Chi-square test*** - The **chi-square test** is used to determine if there is a **significant association** between two **categorical variables**. - In this scenario, both obesity (yes/no) and breast cancer (yes/no) are categorical, making chi-square appropriate to assess if obesity is a risk factor. *Wilcoxon’s signed rank test* - This is a **non-parametric test** used for comparing two related samples or repeated measurements on a single sample, especially when data are not normally distributed. - It is not suitable for assessing the association between two independent categorical variables like obesity and breast cancer. *Student’s paired ‘t’ test* - The **paired t-test** is used to compare the means of two related groups or measurements from the same subject under different conditions (e.g., before and after an intervention). - This test is designed for **continuous data** and would not be appropriate for the categorical variables of obesity and breast cancer. *Student’s unpaired ‘t’ test* - The **unpaired t-test** (also known as independent samples t-test) is used to compare the means of two independent groups for a **continuous outcome variable**. - It is not suitable when both the exposure (obesity) and the outcome (breast cancer) are categorical variables.

Metabolic Integration Indian Medical PG Question 5: Wrong statement about SGLT (sodium-glucose linked transporter):

• A. SGLT2 inhibitors worsen heart failure (Correct Answer)
• B. SGLT2 inhibitors produce weight loss
• C. SGLT1 is present in the intestine and kidneys
• D. SGLT1 has low capacity and high affinity

Metabolic Integration Explanation: ***SGLT2 inhibitors worsen heart failure*** - This statement is incorrect because **SGLT2 inhibitors** have been shown to **improve outcomes in heart failure**, reducing hospitalizations and cardiovascular mortality, even in patients without diabetes. - Their beneficial effects in heart failure are attributed to mechanisms such as **osmotic diuresis**, natriuresis, improved cardiac energetics, and reduced preload and afterload. - Landmark trials like **DAPA-HF** and **EMPEROR-Reduced** demonstrated significant benefits in heart failure with reduced ejection fraction (HFrEF). *SGLT2 inhibitors produce weight loss* - **SGLT2 inhibitors** cause **glucosuria** (excretion of glucose in the urine), leading to a loss of calories and subsequent modest weight loss (2-3 kg). - This effect is a common and beneficial side effect, contributing to improved metabolic profiles in patients with type 2 diabetes. *SGLT1 is present in the intestine and kidneys* - **SGLT1** is the primary transporter responsible for glucose absorption in the **small intestine** and is also found in the **kidneys' S3 segment** of the proximal tubule. - In the kidneys, it plays a minor role in glucose reabsorption compared to SGLT2, but it is critical for dietary glucose absorption. *SGLT1 has low capacity and high affinity* - **SGLT1** is characterized by its **high affinity** for glucose (Km ~0.4 mM), allowing it to efficiently reabsorb glucose even at low concentrations. - However, it has a **lower capacity** compared to SGLT2, meaning it reabsorbs a smaller absolute amount of glucose despite its strong binding.

Metabolic Integration Flashcard 1 of 5

Question: After three days of starvation, the main source of energy for the brain becomes _____ from adipose stores

Answer: ketone bodies

Metabolic Integration Flashcard 2 of 5

Question: Increased glucagon (fasting) leads to increased cAMP and protein kinase A, thus _____ activity of FBPase-2 and decreasing activity of PFK-2

Answer: increasing

Metabolic Integration Flashcard 3 of 5

Question: The number of insulin receptors is _____ in starvation and decreased in obesity

Answer: increased

Metabolic Integration Flashcard 4 of 5

Question: _____ reactions are chemical reactions that form intermediates of a metabolic pathway.

Answer: Anaplerotic

Metabolic Integration Flashcard 5 of 5

Question: In a person starving for more than 18 hours, the source of energy is _____.

Answer: gluconeogenesis