Diabetes Flashcards
Which hormones lead to decrease of glucose? Increase?
There are several hormones that lead to an increase in blood glucose (glucagon, epinephrin, cortisol, GH)
There is only one that decreased blood glucose- insulin
Which cells produce insulin? Glucagon?
Insulin- b-cells
Glucagon: a-cells
What is the biggest producer and user of glucose in fasted state? What are other sources and users
Producer: liver
User: brain (has GLUT1 transporter that doesn’t require insulin to be activated)
Other source: reabsorption by kidneys
Other users: Liver, Muscle + fat, Kidney
Predominant hormone basal vs post-prandial states
Basal: glucagon
Post-prandial: insulin
What is the biggest source and user of glucose in postprandial state?
Source: gut
User: liver, muscle and CNS consume roughly equal amounts
Concentration of insulin and glucagon: Diabetic and healthy subjects
Glucose:
Healthy- Increase after meals and then decrease
Diabetes: higher increase, slower decrease
Insulin:
Healthy- rapid and large spike
Diabetes- almost to increase + delayed
Glucagon:
Healthy- drop after a meal due to insulin presence
Diabetes- excessive glucagon level, non-inhibited by insulin
Is only insulin response varied in diabetes>
both insulin and glucagon levels are affected
Insulin action on Glucose metabolism
Increases anabolism as insulin stimulates
▪ Glucose transport (GLUT: muscle and adipose tissue)
▪ Glycogenesis
Decreases catabolism as insulin inhibits:
▪ Gluconeogenesis (liver)
▪ Glycogenolysis (liver and muscle)
Insulin action on Lipid metabolism
↑ Anabolism as Insulin stimulates
▪ Lipogenesis
▪ Synthesis of triglycerides (Adipose tissue)
▪ Synthesis of free fatty acid (Liver)
↓ Anti-Catabolic as insulin inhibits:
▪ Lipolysis
Insulin action
Protein metabolism and electrolytes
↑ Anabolism as Insulin stimulates
▪ Transport of amino acid
▪ Protein synthesis
▪ Electrolytes: Potassium enter into the cell
↓ Anti-Catabolic as Insulin inhibits
▪ Proteins
▪ Protein catabolism
What is first phase insulin?
● The initial burst of insulin; 5-10 minutes after
β-cell is exposed to a rapid increase in Glucose
● Important for decreasing hepatic glucose production, decreasing lipolysis, and to prepare target cells for the action of insulin
what is second phase insulin
after first phase aka acute response, insulin secretion rises more gradually and is directly related to the degree and duration of stimulus
What is the effect on insulin response of administering glucose oraly vs IV
Oral administration results in much bigger insulin response
What are incretins
Incretins are a group of metabolic hormones that trigger insulin release
The main ones are GLP-1 and GIP
What are the initial symptoms of diabetes?
• Increased thirst (polydipsia) • Increased urination (polyuria) • Increased hunger (polyphagia) • Weight loss (type I) or obesity (II) in later stages of T2 there will also be some weight loss
T1DM Age of onset Weight Islet auto- antibodies C-peptide Insulin production First line treatment Family history of diabetes DKA
- Most <25 by can occur at any age (but not before the age of 6 months)
Weight: Usually thin, but with obesity epidemic, can have overweight or obesity
Islet auto- antibodies: Usually present
C-peptide: Undetectable/low
Insulin production- Absent
First line treatment- insulin
Family history of diabetes- Infrequent (5-10%)
DKA- common
T2DM Age of onset Weight Islet auto- antibodies C-peptide Insulin production First line treatment Family history of diabetes DKA
Age of onset: Usually >24 but incidence increasing in adolescents, paralleling increasing rate of obesity in children & adolescents
Weight- >90% at least overweight
Islet auto- antibodies- absent
C-peptide- normal/high
Insulin production- present
First line treatment- Non-insulin antihyperglycemic agents, gradual dependence on insulin may occur
Family history of diabetes- Frequent (75-90%)
DKA- rare
Monogenic diabetes Age of onset Weight Islet auto- antibodies C-peptide Insulin production First line treatment Family history of diabetes DKA
Age of onset- Usually <25 Neonatal diabetes <6 months*
Weight- Similar to general population
Islet auto- antibodies- absent
C-peptide- normal
Insulin production- usually present
First line treatment- Depends on subtype of MODY
Family history of diabetes- Multigenerational, autosomal pattern of inheritance
DKA- Rare (except for neonatal diabetes*)
Is genetics a big factor in T1 and T2
genetics is not that important in T1
much more important in T2
Is T1 a children’s disease?
Not a children disease
42% of people with type 1 diabetes = diagnosis between the ages of 31 and 60
What is DKA? Symptoms?
Diabetic Ketoacidosis (DKA): Complication of severe insulin deficiency leading to hyperglycemia, causing glucosuria, dehydration and ketogenesis to the eventual acidosis. Common symptoms: • Vomiting • Abdominal Pain • Hyperventilation • Lethargy • Confusion • Dehydration • Fruity Breath
What decreases with insulin resitance?
Decrease in:
• Ability of insulin to suppress endogenous glucose production in the liver
• Uptake of glucose in tissues with insulin-dependent glucose transporters (mainly in skeletal muscle)
• Inhibition of lipolysis-> thus more FA gets produced
Pathogenic features of hyperglycaemia in type 2 diabetes
- Increased lypolysis
- Increased glucose reabsorption by kidneys
- Decreased muscle tissue glucose uptake
- Increased hepatic glucose production
- Increased glucagon secretion
- Impaired insulin secretion
Lab values to diagnose diabetes
1) FPG ≥7.0 mmol/L
Fasting = no caloric intake for at least 8 hours
or
2) A1C ≥6.5% (in adults)
Using a standardized, validated assay in the absence of factors that affect the accuracy of the A1C and not for suspected type 1 diabetes
or
3) 2hPG in a 75 g OGTT ≥11.1 mmol/L
or
4) Random PG ≥11.1 mmol/L
Random = any time of the day, without regard to the interval since the last meal