Endocrine and Breast Module - Hyperglycemia Effects

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Questions and Answers

What is the fasting blood glucose range for non-diabetic individuals?

4.0 – 5.4 mmol/L (correct)

5.5 – 6.9 mmol/L

6.0 – 7.5 mmol/L

3.0 – 4.4 mmol/L

Which of the following is a potential consequence of chronic hyperglycaemia?

Increased glucose excretion

Microvascular complications (correct)

Diabetic ketoacidosis

Enhanced insulin sensitivity

What is a typical blood glucose concentration before meals for non-diabetics?

4.0 – 5.9 mmol/L (correct)

5.0 – 6.5 mmol/L

3.0 – 4.5 mmol/L

6.0 – 7.5 mmol/L

Which condition is specifically associated with acute hyperglycaemia?

Diabetic ketoacidosis Signup and view all the answers

What is the hemoglobin A1C target range for non-diabetic individuals?

4.0 – 5.4% Signup and view all the answers

Which hormone is primarily secreted by alpha cells of the pancreas?

Glucagon Signup and view all the answers

What triggers the release of glucagon from alpha cells?

Low blood glucose Signup and view all the answers

How does high blood glucose affect glucagon release?

It inhibits glucagon release. Signup and view all the answers

Which of the following hormones enhances insulin secretion?

GLP-1 Signup and view all the answers

What is the result of low ATP levels due to low glucose on glucagon secretion?

K⁺ channels remain open, promoting glucagon release. Signup and view all the answers

What role does oxyntomodulin play in the body?

It regulates appetite and energy expenditure. Signup and view all the answers

What happens to potassium channels when blood glucose levels are high?

They close, leading to membrane depolarization. Signup and view all the answers

Which pancreatic cells are responsible for glucagon secretion?

Alpha cells Signup and view all the answers

What triggers the release of glucagon?

Low blood glucose levels Signup and view all the answers

What is the primary synthesis site of glucagon in the body?

Alpha cells of the pancreas Signup and view all the answers

Which amino acid level change would most likely prevent hypoglycemia after a meal?

Increased amino acid levels Signup and view all the answers

Which enzyme is responsible for converting proglucagon into mature glucagon?

Prohormone convertase 2 (PC2) Signup and view all the answers

What is the role of glucagon in blood glucose regulation?

Increases blood sugar levels Signup and view all the answers

Which condition is characterized by hypoglycemia due to excess insulin?

Insulin dependent hypoglycemia Signup and view all the answers

What is the normal blood glucose range for non-diabetic individuals?

70-120 mg/dL Signup and view all the answers

How does the body respond to low blood glucose levels?

Stimulates glucagon release Signup and view all the answers

What is the primary function of glucagon in the liver?

Promotes glucose release through glycogen breakdown Signup and view all the answers

Which of the following hormones is primarily responsible for the release of incretins?

Food intake Signup and view all the answers

What occurs during gluconeogenesis?

Synthesis of glucose from non-carbohydrate sources Signup and view all the answers

What effect do incretins have on glucagon secretion?

Inhibit glucagon secretion Signup and view all the answers

Which of the following statements about glucagon is true?

It enhances lipolysis for fatty acid breakdown. Signup and view all the answers

The signal transduction pathway of glucagon involves which of the following activities?

Phosphorylation of downstream enzymes Signup and view all the answers

Which tissue does glucagon primarily target to increase amino acid uptake?

Liver Signup and view all the answers

What is the result of glucagon binding to its G-protein coupled receptor?

Activation of adenylate cyclase Signup and view all the answers

Which factor is responsible for inhibiting glucagon secretion?

High blood glucose Signup and view all the answers

How does low blood glucose trigger glucagon secretion?

By keeping K⁺ channels open and allowing Ca²⁺ influx Signup and view all the answers

What role do high plasma amino acids play in glucagon secretion?

They stimulate glucagon release Signup and view all the answers

What effect does somatostatin have on glucagon secretion?

It inhibits glucagon release Signup and view all the answers

During fasting, glucagon secretion occurs at which of the following levels?

Constant low levels for glucose homeostasis Signup and view all the answers

Which physiological state is most likely to lead to increased glucagon release?

In response to intense stress or exercise Signup and view all the answers

Which of the following describes glucagon’s effect on glycogen stores?

It stimulates glycogenolysis Signup and view all the answers

What is the primary effect of glucagon on fatty acids?

Promotes fatty acid oxidation Signup and view all the answers

Which process is directly inhibited by glucagon?

Glycogenesis Signup and view all the answers

Which hormone enhances insulin secretion in a glucose-dependent manner?

GLP-1 Signup and view all the answers

What initiates the signal cascade when glucagon binds to its receptor?

Production of cAMP Signup and view all the answers

What is the effect of low plasma fatty acids on glucagon secretion?

It stimulates glucagon secretion to promote fat breakdown. Signup and view all the answers

Which of the following factors does NOT stimulate incretin release?

Fasting Signup and view all the answers

Which factor directly inhibits glucagon release at high blood glucose levels?

Insulin Signup and view all the answers

What is the overall metabolic role of glucagon in response to low blood glucose levels?

To enhance glucose production from non-carbohydrate sources Signup and view all the answers

What is a primary action of glucagon in response to low blood glucose levels?

Promoting gluconeogenesis Signup and view all the answers

How does glucagon primarily affect the liver?

Enhances amino acid uptake for gluconeogenesis Signup and view all the answers

During which physiological state is glucagon secretion most likely to increase?

During rigorous exercise Signup and view all the answers

Which hormone released by delta cells inhibits both glucagon and insulin secretion?

Somatostatin Signup and view all the answers

During fasting, glucagon is continually secreted at low levels to achieve which of the following?

Maintain glucose homeostasis Signup and view all the answers

Which of the following factors is least likely to increase glucagon secretion?

High blood glucose Signup and view all the answers

What occurs to potassium channels when there are low ATP levels due to low glucose?

Potassium channels remain open, facilitating membrane depolarization. Signup and view all the answers

What is the overall primary goal of glucagon secretion?

To increase blood glucose levels Signup and view all the answers

What role does the prohormone convertase 2 (PC2) enzyme play in glucagon synthesis?

It cleaves proglucagon to produce mature glucagon. Signup and view all the answers

What physiological condition is likely to stimulate glucagon release from the pancreas?

Fasting. Signup and view all the answers

Which form of hypoglycemia is specifically associated with the ingestion of alcohol?

Alcohol-induced hypoglycemia. Signup and view all the answers

Which of the following best describes the mechanism of glucagon release due to low glucose levels?

Inhibition of ATP production, causing K⁺ channels to remain open Signup and view all the answers

Which tissue-specific processing can occur to proglucagon depending on the site of synthesis?

It can yield different peptides other than glucagon. Signup and view all the answers

Which hormone acts to enhance the incretin effect on insulin secretion?

Glucagon-like peptide 1 (GLP-1) Signup and view all the answers

What effect does high blood glucose have on alpha cells in the pancreas?

Inhibits glucagon secretion Signup and view all the answers

What is the primary effect of glucagon when released into the bloodstream?

To raise blood glucose levels. Signup and view all the answers

What is the main factor that inhibits glucagon secretion?

Elevated blood glucose levels. Signup and view all the answers

Which type of release is triggered in alpha cells in response to low blood glucose?

Glucagon exocytosis Signup and view all the answers

During which process might glucagon secretion increase significantly?

During endurance exercise. Signup and view all the answers

How does insulin inhibit glucagon release from alpha cells?

By increasing ATP levels Signup and view all the answers

What is the composition of mature glucagon?

It consists of 29 amino acids. Signup and view all the answers

What is the effect of epinephrine on glucagon release?

It stimulates glucagon release Signup and view all the answers

Study Notes

Effects of Acute and Chronic Hyperglycemia

The lecture covered the effects of acute and chronic hyperglycemia in MED year 2, Endocrine and Breast module.
The lecturer was Dr. Jeevan Shetty.
The lecture was on January 2025.

Learning Outcomes

Students will be able to describe the normal range of blood glucose concentrations.
Students will be able to recollect the diagnostic criteria for hyperglycemia and diabetes.
Students will be able to describe the causes, symptoms, diagnosis, and treatment of acute hyperglycemia, especially diabetic ketoacidosis.
Students will be able to describe the causes and symptoms of chronic hyperglycemia and illustrate its molecular physiology and consequences.

Recommended Target Glucose Ranges

NICE provides recommended target blood glucose levels.
Ranges vary based on diabetes type (non-diabetic, type 1, type 2) and age.
A1C values, fasting blood glucose, pre-meal glucose, and 2-hour post-prandial glucose levels are included in the ranges.
Individualization of targets crucial, considering patient factors (age, comorbidities).
For adults with hypoglycemia-causing medications, an HbA1c target of 53 mmol/mol (7.0%) is recommended.

Diagnostic Criteria for Hyperglycemia and Diabetes

Fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dL) is a diagnostic criterion for hyperglycemia/diabetes.
Random plasma glucose ≥ 11.1 mmol/L (200 mg/dL) is a diagnostic criterion for hyperglycemia/diabetes.

Hyperglycemia

Fasting blood glucose ≥ 7.0 mmol/L
2-hour blood glucose (OGTT) ≥ 11.1 mmol/L
Acute hyperglycemia: Blood glucose ≥ 8-15 mmol/L, symptomatic ≥ 15-20 mmol/L, glycosuria threshold ≈ 8-10 mmol/L

Common Causes of Hyperglycemia

Diabetic
- T1DM: immune-mediated destruction of β-cells in the pancreas.
- T2DM: β-cells present but abnormal glucose metabolism and insulin secretion.
Non-Diabetic
- Stress, Cushing's syndrome, pancreatic diseases, infections, medications (glucocorticoids, β-blockers, thiazides, etc.), lifestyle factors (diet, inactivity), other endocrine disorders

Diagnostic Glucose Ranges

Patients presenting with possible diabetes symptoms: urine test for glucose/ketones, venous blood glucose (fasting or random).
Diagnosis confirmed by fasting plasma glucose ≥ 7.0 mmol/L or random plasma glucose ≥ 11.1 mmol/L.
Oral glucose tolerance tests indicated in certain cases (fasting 6.1-7.0 mmol/L, random 7.8-11.0 mmol/L).
HbA1c not a definitive diagnostic test for diabetes or intermediate hyperglycemia.

Self-Monitoring of Blood Glucose (SMBG)

SMBG recommended for patients on multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (insulin pump).
Timing: pre-meal, bedtime, pre/post exercise, before activities (e.g., driving).
Frequency depends on insulin regimen and factors like patient's need and their medications (e.g., hypoglycemia-causing medications)

HbA1c

HbA1c reflects average glucose levels a cell has been exposed to during its life cycle.
Combining SMBG and HbA1c essential for complete glucose control assessment.
HbA1c monitored every 3 months; once target achieved, every 6 months.

Acute Hyperglycemia

Acute hyperglycemia causes, symptoms, diagnosis, and treatment, especially diabetic ketoacidosis, are covered.

(Acute) Metabolic Effects of Insulin Deficiency

Effects on carbohydrate, fat, and protein metabolism discussed, including hyperglycemia, glucosuria, osmotic diuresis, dehydration, polydipsia, polyphagia, muscle wasting, and weight loss.
Mechanisms of these effects are described.
Insulin deficiency increases hepatic glucose output and decreases glucose uptake in peripheral tissues, resulting in hyperglycemia.
Reduced glucose uptake in peripheral tissues contributes to hyperglycemia.

Hyperglycemia Symptoms

Symptoms include glycosuria, polyuria, polydipsia, polyphagia, electrolyte loss (Na+, K+), and weight loss.
Additional symptoms: dehydration, abdominal pain, vomiting, altered mental status (lethargy, somnolence, stupor, coma).

Diabetic Ketoacidosis (DKA)

Most common acute hyperglycemic emergency in people with diabetes mellitus, especially in T1DM, but can also occur in T2DM.
Triggered by intercurrent illnesses, decreased appetite, or reduced insulin dose. Stress can also be a precipitating factor, notably in T2DM.

Diabetes Ketoacidosis (DKA) - Causes and Pathogenesis

Insufficient insulin results in increased hepatic glucose production and reduced glucose uptake in peripheral tissues resulting in hyperglycemia.
Insufficient insulin leads to increased fatty acid metabolism and ketogenesis.
This process results in the production of ketones which lowers blood pH, causing a metabolic acidosis.
Glycogenolysis and gluconeogenesis increase glucose production when carbohydrate stores are insufficient.

DKA - Diagnosis

DKA diagnosed via a triad of hyperketonaemia, hyperglycemia, and metabolic acidosis.
Urine/serum ketones, blood glucose, and venous bicarbonate/pH assessed.
Anion gap measurement (Na+ -[Cl- + HCO3-]) is a significant indicator.
Elevated serum ketones, significant hyperglycemia, and metabolic acidosis, with an anion gap greater than 12 mmol/L, signify this condition.

DKA - Treatment

IV fluid replacement crucial, up to 6-9L fluid deficit.
Insulin administration is critical, correcting hyperglycemia and ketosis.
Electrolyte imbalances are corrected.
Continuous monitoring vital throughout the treatment phase.

DKA - Management

A detailed checklist provided outlining treatment milestones in phases (0–6 h, 6–12 h, 12–24 h).
Immediate treatment in hospital, preferably by a diabetes specialist and in a high dependency area.
Frequent clinical and biochemical monitoring, particularly in high-risk groups.
Precipitating factors (like infection) acknowledged and addressed.

Hyperosmolar Hyperglycemic State (HHS)

Hyperglycemia (often over 600 mg/dL) with severe dehydration, contrasted with DKA.
Acidosis is absent, and ketone production is limited by some level of endogenous insulin.
HHS treatment includes fluid replacement and insulin therapy.

Chronic Hyperglycemia

Chronic hyperglycemia causes, symptoms, and molecular physiology/consequences are covered.
Chronic complications include non-enzymatic glycosylation (NEG) and osmotic damage.

Effects of Chronic Hyperglycemia: Chronic Complications

Non-enzymatic glycosylation (NEG):
- Glucose attaches to proteins/lipids without enzyme involvement.
- Cellular damage, leading to diabetic complications (retinopathy, nephropathy, neuropathy, atherosclerosis).
Osmotic cellular damage:
- Glucose enters the cells, converting to sorbitol and increasing intracellular osmotic pressure.
- Results in further tissue damage in organs such as the eye lens, nerves, kidneys etc.

Microvascular and Macrovascular Complications

Microvascular: Diabetic nephropathy, retinopathy, neuropathy.
Macrovascular: Damage to large blood vessels in the heart, brain, legs, and feet, contributing to heart disease, stroke, and peripheral vascular disease.

Review Questions

In insulin deficiency, which metabolic pathway is more active? (Ketogenesis)
What type of acid-base disorder is most common in uncontrolled DM patients? (Metabolic acidosis)
Which intracellular ion is lost in DKA? (Potassium)

Additional Information

Includes sources for further reading (books and websites).

Questions?

Contact information for Dr. Shona Pfeiffer, Ph.D., regarding any further queries.

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Description

This quiz focuses on the effects of acute and chronic hyperglycemia as discussed in the MED year 2 Endocrine and Breast module. Students will explore blood glucose ranges, diagnostic criteria for diabetes, and treatment options for hyperglycemia. Assess your understanding of the physiological and pathological implications of these conditions.