Pathophysiology of Diabetes Exam 2 Flashcards
What is the primary energy source?
glucose
What is the primary macronutrient used for energy?
carbohydrate (CHO)
What are processes of catabolism of CHO?
- Glycogenolysis
- Glycogenesis
What are processes of synthesis of glucose?
Gluconeogenesis
Glycogenolysis
Process of breaking down CHO for quick energy source
Glycogenesis
- Process of converting CHO to glycogen for storage for later use.
- Stored in skeletal muscle, liver, and fat (adipose) tissue
Gluconeogenesis
- Process of synthesizing glucose during glucose deficiency
- Liver (primary) and kidneys
What are the cells that exists in the pancreas?
- β-cells
- α-cells
β-cells
Produce insulin
α-cells
Produce glucagon
What is insulin secretion regulated by?
- various nutrients
- incretin hormones
- pancreatic hormones
- autonomic neurotransmitters
What is the primary stimulus for insulin secretion?
- orally administered glucose (when you eat)
- called the incretin effect
Where does secreted insulin goes first?
into the portal vein to the liver to stop glucose production
What is basal release?
means insulin is continuously secreted from the pancreas
What is bolus release?
- insulin secreted due to consumption
- first phase: peak in insulin secretion, shuts down hepatic glucose production
- second phase: delayed
What promotes glucose uptake?
insulin
general actions of insulin
- Promotes lowering of blood glucose
- Promotes storage of glucose
- Promotes potassium uptake
function of insulin in the liver
- Glucose uptake
- Stimulates glycogen storage
- Stimulates synthesis of triglycerides
- Inhibits glycogenolysis
function of insulin in muscle
- Increase glucose uptake
- Enhances glycogen synthase
- Increases uptake of amino acids
- Inhibits glycogen phosphorylase
function of insulin in fat
- Increase glucose uptake
- Increase triglyceride production
- Stimulates lipoprotein lipase
What is the major source of elimination for endogenous insulin?
liver
Glucagon-like peptide 1 (GLP-1)
- one of the incretin hormones
- Released from the L cells in the intestine in response to glucose and other nutrients upon eating
- Stimulates insulin secretion (glucose dependent)
- Suppresses appetite and promotes weight loss
- Slows gastric emptying
- Metabolized rapidly (1-2 min) by dipeptidyl peptidase 4 (DPP-4)
Glucose-dependent insulinotropic polypeptide (GIP)
- one of the incretin hormones
- Released from K cells in response to glucose and fat intake
- Promotes insulin biosynthesis
- Promotes insulin secretion (glucose dependent)
- May prevent apoptosis
- May stimulate glucagon
- Metabolized rapidly (5-7 min) by DPP-4
Amylin
- Released with insulin from β-cell
* Promotes lowering glycemia by: slowing gastric emptying, suppressing glucagon, increasing satiety
Glucagon
- Synthesized and secreted from pancreatic alpha cells
- Inhibited by glucose
- Promotes increasing glucose
- Primary effect is on the liver
Glucagon effect
In the liver:
- Stimulates: Glycogenolysis, Gluconeogenesis, Fatty acid oxidation, Ketogenesis
- Inhibits: Glycogen synthesis, Fatty acid synthesis
What are the counter-regulatory hormones?
- Glucagon
- Epinephrine
- Cortisol
- Growth hormone
Epinephrine effect
Stimulates hepatic glucose release via glycogenolysis and lipolysis
Cortisol effect
Stimulates hepatic uptake of amino acids which can be used to produce glucose
Growth hormone
Stimulates lipolysis and inhibits glucose uptake in muscle and adipose tissue
What is hemoglobin A1c?
- Marker of glycemia over 2-3 month period
* Lab is a % of hemoglobin A1 molecule with glucose bound
What is a hemoglobin lifespan?
120 days
How can accuracy be lost in the A1c test?
if the patient has:
- hemoglobinopathies
- uremia
- hemorrhage
- hemolytic disorders
normal value for A1c
4-5.6%
normal preprandial BS
<100 mg/dL
normal postprandial BS
<140 mg/dL
normal value for A1c for someone diagnosed with DM
<7%
normal preprandial BS for someone diagnosed with DM
80-130 mg/dL
normal postprandial BS for someone diagnosed with DM
<180 mg/dL
normal bedtime BS for someone diagnosed with DM
100-180 mg/dL
correlate A1c to the estimated average blood glucose
- A1c 10 = 240 mg/dL
* every 1 digit of A1c = 30 mg/dL
A1c monitoring
- Every 3 months when A1c not at goal
- Every 6 months when A1c at goal
- Every 12 months when A1c within pre-diabetes range
causes of hyperglycemia
- Associated with suboptimal medication doses (those with DM)
- Excessive glucose release from the liver
- Excessive ingestion of CHO
- Stress, illnesses, medications
symptoms of hyperglycemia
- Polyuria / Glucosuria
- Polyphagia
- Polydipsia
- Weight loss
- Blurry vision
- Paresthesia
- Muscle weakness
- Altered level of consciousness
- Lethargy
- Headache
- Postural hypotension
- DKA or HHS
symptoms of hyperglycemia: Polyuria / Glucosuria
- happens when serum glucose > 180mg/dL and glucose spills into urine
- water follows glucose -> osmotic diuresis
- free water and electrolytes are lost
symptoms of hyperglycemia: Polyphagia
increased hunger
symptoms of hyperglycemia: Polydipsia
- unquenchable thirst
- Caused by increasing osmolality (from hyperglycemia/free water loss)
- ↑glucose = ↑osmolality, then hypothalamus induces sensation of thirst
symptoms of hyperglycemia: Weight loss
- Initially associated with depletion of water, glycogen and triglyceride stores
- Then due to reduced muscle mass
- Loss of 10-30 pounds can occur
symptoms of hyperglycemia: Blurry vision
in a hyperosmolar state, water enters the lens resulting in modest swelling
symptoms of hyperglycemia: Paresthesia
nerve damage from sustained hyperglycemia
symptoms of hyperglycemia: Muscle weakness
due to catabolism of muscle
symptoms of hyperglycemia: Altered level of consciousness
due to hyperosmolality
symptoms of hyperglycemia: Headache
most patients describe as throbbing headache
symptoms of hyperglycemia: Postural hypotension
due to depleted plasma volume
hypoglycemia classifications
- hypoglycemia alert value
- clinically significant hypoglycemia
- severe hypoglycemia
hypoglycemia classifications: hypoglycemia alert value
- ≤ 70 mg/dL
* sufficiently low for treatment with fast-acting CHO and dose adjustment of glucose-lowering therapy
hypoglycemia classifications: clinically significant hypoglycemia
- < 54 mg/dL
* sufficiently low to indicate serious, clinically important hypoglycemia
hypoglycemia classifications: severe hypoglycemia
- no specific glucose threshold
* hypoglycemia associated with severe cognitive impairment requiring external assistance for recovery
causes of hypoglycemia
- Excessive quantity of medication (those with DM)
- More than usual physical activity
- Inadequate food intake
symptoms of hypoglycemia
- Trembling/shaking
- pounding heart
- tachycardia
- changes in body temperature
- sweating
- tingling in extremities
- Slow thinking
- blurred vision
- slurred speech
- lack of coordination
- numbness
- dizziness
- fatigue/sleepiness
- trouble concentrating
- coma
- Hunger, nausea
- weakness
- headache
- general strange feeling
- social behavioral changes
How are autonomic symptoms happening during hypoglycemia?
Epinephrine is released
hypoglycemic unawareness
Experiencing hypoglycemia without realizing it
What can increase the risk of having hypoglycemic unawareness?
- Previous episode of hypoglycemia in the past 24 hours
- Multiple episodes of hypoglycemia
- Very tight blood glucose control
How would you treat mild hypoglycemia?
- Consume 15-20g of simple CHO
- 3-4 glucose tablets, gel, juice (preferred) • 8-10 lifesavers or 5-6 peppermint candies
- 8oz regular milk
- 4-6oz fruit juice or regular soda
- 1 tablespoon honey
- Recheck BS in 15-20 minutes
- Repeat treatment if necessary
How would you treat severe hypoglycemia?
Administer glucagon (stimulates liver to release stored glucose)
What is a common adverse effect with glucagon?
- vomit
- turn pt on their side
What are pre-diabetes markers?
- Impaired fasting glucose (IFG): 100-125 mg/dL
* Impaired glucose tolerance (IGT): OGTT result with 2 hour plasma glucose of 140-199 mg/dL
How do you classify prediabetes?
- Patients who meet IFG or IGT criteria
* A1c 5.7-6.4%
How can you diagnose a patient with diabetes?
if they have any of the following:
• A1c ≥ 6.5%
• Fasting plasma glucose ≥ 126 mg/dL, or
• Symptoms of hyperglycemia and random plasma glucose ≥ 200 mg/dL, or
• OGTT with 2 hr plasma glucose ≥ 200 mg/dL
pathogenesis of DM I
- born with a predisposition to produce antibodies to β-cells (autoimmune disorder)
- 90% of pts have at least one autoantibody
- Trigger: environmental or infectious
- Autoantibodies begin to destroy β-cells
What happen when autoantibodies begin to destroy β-cells?
Insulin and amylin production decline to 0 (or close to it)
What is the honeymoon phase?
pt has DM I but pancreas still has some insulin it’s secreting so it doesn’t seem as if pt has DM I
What are the four antibodies that are found in someone with DM I?
- Glutamic acid decarboxylase 65 (GAD65)
- Islet cell antibody (ICA)
- Insulin autoantibody (IAA)
- Tyrosine phosphatases antibody (IA-2)
What are risk factors for DM I?
- Family history of DM1 or auto-antibodies
* Known presence of auto-antibodies
What are the screening guidelines for DM I?
- No indication for screening the general population
- Based on clinical presentation
- No good data on targeted screening
- Some clinicians will screen for auto-antibodies in patients with a family history of type 1 DM (TrialNet)
What are laboratory markers of DM I?
- Serum insulin – low
- C-peptide – low
- Autoantibodies – present
- Blood glucose - high 83
- Glucosuria – present
- A1c – high
- Ketones – often present
Diabetic Ketoacidosis (DKA)
- Excess ketone production → ketonemia → ketoruia → diabetic ketoacidosis
- life threatening
What are symptoms of DKA?
- Abdominal pain
- fruity odor on breath
- CNS depression
- coma
What are physical findings of DKA?
- Tachycardia
- dehydration
- tachypnea / Kussmaul respirations
pathogenesis of DM II
- Early resistance to insulin resulting in pancreas compensating with hyperinsulinemia, but normal glycemia
- Progression of disease results in worsening hyperglycemia until diagnostic thresholds are crossed
What happens overtime in DM II?
impaired glucose tolerance (IGT) (inability to compensate for rising blood glucose after meals) and impaired fasting tolerance (IFT) (poor control in the fasting state) develop
What contributes to DM II?
- Diminished insulin sensitivity
- Up-regulation hepatic glucose production
- Impaired β-cell function
What are risk factors for DM II?
- BMI ≥ 25 kg/m2 or ≥ 23 kg/m2 in Asian-Americans
- History of impaired glucose tolerance or impaired fasting glucose
- Physical inactivity
- Family history of diabetes (first degree)
- High risk ethnicity (Black, Latino, Native American, Asian American, Pacific Islander)
- History of GDM
- HTN, low-HDL, or triglycerides over 250mg/dL
- Polycystic ovary disease
- Other condition associated with insulin resistance
- History of cardiovascular disease
- Metabolic syndrome
What are the qualifiers to diagnose metabolic syndrome?
- Diagnosis (3 of 5):
• Abdominal obesity (waist circumference >40” M, >35” W)
• Elevated triglycerides (≥150 mg/dL)
• Elevated blood pressure (≥130/85 mmHg or on med)
• Elevated fasting glucose (> 110 mg/dL)
• Low HDL (<40 mg/dL M, <50 mg/dL W)
What can metabolic syndrome imply?
- Inflammation
- Diabetic dyslipidemia
- Pro-thrombotic state
- Endothelial dysfunction and vascular abnormalities
- Increase risk for cardiovascular disease
Diabetic dyslipidemia
- More atherogenic LDL (smaller and more dense penetrating blood vessel walls easier resulting in plaques)
- High triglycerides
- Low HDL
What are the screening guidelines for DM II?
- All overweight adults with one additional risk
- All adults, regardless of risk, at age 45 years
- If the test is normal, repeat every 3 years
- If the test is in the area of prediabetes, repeat every year
What are laboratory markers of DM II?
- Serum insulin and C-peptide - usually elevated or normal at diagnosis
- Autoantibodies for β-cells - absent
- Glycemia – elevated and varied
- A1c - elevated
- Glucosuria - present if glycemia is high enough
- Ketone production - uncommon in DM2
- Hyperglycemic hyperosmolar syndrome
Hyperglycemic hyperosmolar syndrome (HHS)
- Similar to DKA in many ways, but no ketones
- Relative (not absolute) insulin deficiency
- Up-regulated hepatic glucose production
- Extreme hyperglycemia – often > 1000mg/dL
- Osmotic diuresis leading to intravascular volume depletion and dehydration
What are the signs / symptoms of HHS?
- lethargy
- confusion
- hypotension
- tachycardia
What are the risks of having gestational diabetes?
- Macrosomia (having a large baby)
- Excessive maternal weight gain (>40 lbs)
- Preeclampsia
- Still birth
- Neonatal hypoglycemia, hyperbilirubinemia, hypocalcemia, respiratory distress syndrome
- ↑ risk of baby developing DM2, obesity, or metabolic syndrome
- ↑ risk of maternal development of DM2
