Diabetes Mellitus Flashcards
What hormones are produced by the pancreas, and by which cells?
- Insulin by β cells.
- Glucagon by α cells.
- Somatostatin by δ cells.
What are the primary functions of insulin?
Carbohydrates:
1. Increases glucose uptake.
2. Increases glycogen synthesis (storage).
3. Decreases gluconeogenesis.
4. Increases glycolysis (muscle).
5. Increases conversion of carbohydrates to fat (lipogenesis).
Fats:
1. Decreases lipolysis (fat breakdown).
Proteins:
1. Increases amino acid uptake.
2. Increases protein synthesis.
It ultimately results in decreased blood glucose.
What is the primary function of glucagon?
Regulates blood glucose by promoting glycogen breakdown and glucose release from the liver.
It ultimately results in increased blood glucose.
What is the role of somatostatin in the pancreas?
Inhibits the release of insulin and glucagon and regulates the endocrine system.
What complications arise from a lack of insulin?
Severe hyperglycemia, leading to retinopathy, nephropathy, neuropathy, and cardiovascular complications.
How is diabetes mellitus (DM) characterized?
As a group of heterogeneous syndromes causing elevated blood glucose and insufficient insulin secretion.
What are the four clinical classifications of diabetes?
- Type 1: Insulin-dependent.
- Type 2: Non-insulin-dependent.
- Gestational diabetes.
- Diabetes due to other factors (such as genetic defects, pancreatic disorders, or medications).
Why doesn’t Type 1 diabetes respond to oral hypoglycemic drugs?
Because it requires exogenous insulin due to absolute insulin deficiency.
How is Type 2 diabetes managed, and what may be required in late-stage disease?
Managed with oral hypoglycemic agents (OHAs); insulin may be required in late-stage disease.
Who is more likely to develop gestational diabetes?
Obese pregnant women.
What are some causes of diabetes due to other factors?
Drugs like thiazides and loop diuretics, diseases (e.g., pancreatitis), and chemicals like alloxan and streptozotocin.
When is Type 1 diabetes most commonly diagnosed?
During puberty or early adulthood.
What causes the absolute deficiency of insulin in Type 1 diabetes?
Massive β-cell necrosis.
What mediates the autoimmune process in Type 1 diabetes?
An autoimmune process directed against β-cells, possibly due to virus invasion or chemical toxins.
What are the common symptoms of Type 1 diabetes?
- Polydipsia (excessive thirst).
- Polyphagia (excessive hunger).
- Polyuria (frequent urination).
- Weight loss.
What life-threatening condition is associated with Type 1 diabetes?
Ketoacidosis.
What is ketoacidosis and how does it relate to Type 1 diabetes?
Ketoacidosis is a life-threatening condition where high blood sugar leads to the production of ketones, causing blood acidity. It occurs in Type 1 diabetes due to insufficient insulin.
Compare the effects of insulin between people without diabetes and those with diabetes.
Normally, in patients without diabetes, constant β-cell secretion maintains low basal levels of circulating insulin. This suppresses:
- Lipolysis (breakdown of fats into fatty acids and glycerol).
- Proteolysis (breakdown of proteins into amino acids.
- Glycogenolysis (breakdown of glycogen into glucose).
Without insulin:
- Increased lipolysis leads to elevated levels of free fatty acids in the blood, contributing to ketoacidosis.
- Increased proteolysis results in muscle wasting and elevated amino acid levels in the blood, contributing to gluconeogenesis and further raising blood glucose levels.
- Increased glycogenolysis leads to elevated blood glucose levels, contributing to hyperglycemia.
What is HbA1c and how does it relate to Type 1 diabetes management?
HbA1c, or glycated hemoglobin, measures the average blood glucose levels over the past 2-3 months. In Type 1 diabetes, maintaining accepted HbA1c levels helps control hyperglycemia and ketoacidosis, preventing long-term complications.
Why is exogenous insulin necessary for Type 1 diabetes patients?
To control hyperglycemia and ketoacidosis and maintain accepted HbA1c levels to avoid long-term complications.
What is a significant limitation of β-cells in Type 1 diabetes?
They cannot maintain normal insulin secretion or respond to variations in circulating glucose and amino acids.
Describe insulin secretion after the ingestion of a meal.
A burst of insulin secretion occurs within 2 minutes after ingesting a meal, in response to transient increases in circulating glucose and amino acids. This lasts for up to 15 minutes, followed by the postprandial secretion of insulin.
Without functional β cells, those with type 1 diabetes can neither maintain basal secretion of insulin nor release a bolus of insulin to respond to variations in circulating glucose.
What is the most common type of diabetes?
Type 2 diabetes.
What factors influence Type 2 diabetes?
- Genetic factors.
- Aging.
- Obesity.
- Peripheral insulin resistance.
How do the metabolic alterations in Type 2 diabetes compare to Type 1?
They are milder in Type 2 diabetes.
Does ketoacidosis occur in Type 2 diabetes?
No.
What is the status of β-cell function in Type 2 diabetes?
The pancreas retains some β-cell function, but insulin secretion is variable and insufficient for glucose homeostasis.
What is the major cause of Type 2 diabetes?
Lack of sensitivity of target organs to insulin.
What is the treatment goal for Type 2 diabetes?
To prevent long-term complications.
What happens to β-cell function as Type 2 diabetes progresses?
β-cell function declines, and insulin therapy may be required to maintain satisfactory serum glucose levels.
Why can’t insulin be taken orally?
It is degraded in the GIT due to it being a polypeptide hormone, so it must be administered by subcutaneous injection.
What is the precursor of insulin?
Pro-insulin, which is inactive and undergoes proteolytic cleavage to form insulin and C peptide, both of which are secreted by β cells of the pancreas.
Why is measuring C peptide levels a better index of insulin levels?
Because insulin undergoes significant hepatic and renal extraction, plasma insulin levels may not accurately reflect insulin production.
C peptide is secreted in equimolar amounts with insulin, providing a more accurate measure of endogenous insulin secretion.
What are the main regulators of insulin secretion?
Blood glucose (most important), certain amino acids, gastrointestinal hormones, and autonomic mediators.
How does glucose intake lead to insulin secretion in the pancreas?
Glucose is phosphorylated by glucokinase, producing glucose-6-phosphate. This leads to an increase in ATP production, which inhibits potassium efflux by closing ATP-sensitive potassium channels, causing depolarization. This depolarization opens voltage-gated calcium channels, increasing intracellular calcium, which triggers insulin secretion.
What are the effects of insulin on carbohydrates?
Insulin increases glucose uptake, glycogen synthesis, glycolysis, and lipogenesis; and decreases gluconeogenesis.
Glycogen Synthesis: Formation of glycogen from glucose.
Glycolysis: Breakdown of glucose to produce energy.
Lipogenesis: Conversion of glucose into fatty acids and triglycerides.
Gluconeogenesis: Production of glucose from non-carbohydrate sources.
What are the effects of insulin on fat and protein metabolism?
Insulin decreases lipolysis and increases amino acid uptake for protein synthesis.
Lipolysis: The breakdown of triglycerides into glycerol and free fatty acids. This process releases stored energy from fat cells and is inhibited by insulin.
Why do insulin preparations vary in onset and duration of activity?
Due to differences in amino acid sequences of the polypeptides and the type of formulation.
Why do lispro, aspart, and glulisine have a faster onset and shorter duration than regular insulin?
They do not aggregate or form complexes.
What is the characteristic of long-acting insulins like glargine and detemir?
They show prolonged, flat levels of the hormone following injection (i.e., they maintain steady insulin levels without peaks, providing consistent glucose control over a long period.)
What is the most serious and common adverse reaction to an overdose of insulin?
Hypoglycemia.
What are some other adverse reactions to insulin besides hypoglycemia?
- Weight gain.
- Lipodystrophy (less common with human insulin).
- Allergic reactions.
- Local injection site reactions.
Which insulin preparations are considered rapid-acting and short-acting?
- Regular insulin.
- Insulin lispro.
- Insulin aspart.
- Insulin glulisine.
Which type of insulin can be given IV in emergencies?
Regular insulin.
What is the advantage of rapid-acting insulins like lispro over regular insulin?
They are absorbed more rapidly, leading to quicker action.
Which insulin has the lowest risk of lipodystrophy?
Regular insulin.
Why are rapid-acting insulins usually administered?
To mimic the mealtime (prandial) release of insulin.
When are rapid-acting insulins typically administered?
Immediately before or following a meal.
What does Pregnancy Category B mean for insulin?
It indicates that animal studies have not shown risk to the fetus, but there are no well-controlled studies in pregnant women.
How do rapid-acting insulins like lispro compare to regular insulin in terms of absorption?
Rapid-acting insulins have more rapid absorption after subcutaneous injection, leading to quicker action.
What is another name for Neutral Protamine Hagedorn (NPH) insulin, an intermediate-acting insulin?
Insulin isophane.
How should intermediate-acting insulin (NPH) be administered?
Subcutaneously, never intravenously, due to it being a suspension.
Why does NPH insulin have a delayed absorption?
It forms a less-soluble complex with protamine, delaying absorption and resulting in an intermediate duration of action (it has neutral pH with a positively charged polypeptide).
For which conditions is intermediate-acting insulin NOT useful?
Diabetic ketoacidosis and emergency hyperglycemia.
With what type of insulin is intermediate-acting insulin usually given?
Rapid-acting or short-acting insulin for mealtime control.
What is neutral protamine lispro (NPL) insulin used for?
It is used only in combination with insulin lispro.
What are some premixed combinations of human insulins?
70% NPH plus 30% regular insulin, 50% of each, OR… 75% NPL plus 25% insulin lispro.
Why does the long-acting insulin glargine have an extended action?
Its isoelectric point is lower than human insulin, causing it to precipitate at the injection site.
How does the onset of insulin glargine compare to NPH insulin?
Insulin glargine has a slower onset than NPH insulin.
What is unique about the hypoglycemic effect of insulin glargine?
It is prolonged and has no peak (flat).
