Diabetes Pathophysiology Flashcards
What are the sources of glucose (a primary energy source)?
Food, Glycogen Stores, and Liver
What is the primary macronutrient used for energy?
Carbohydrate CHO
What is catabolism of CHO?
Glycogenolysis
What is the synthesis of CHO called?
Gluconeogenesis or Glycogenesis, it synthesizes glucose during glucose deficiencies
Glycogenolysis is what?
Process of breaking down CHO for QUICK energy
Glycogenesis is what?
Converting CHO to glycogen for storage (skeletal muscle, liver, fat)
Protein synthesis is stimulated by what?
Insulin, because insulin moves glucose from blood into storage
B-Cells in the pancreas produce what?
Insulin and Amylin
A-Cells in the Pancreas produces what?
Glucagon
What hormones are utilized to decrease glycemia?
Insulin, incretin hormones, and amylin
What hormones are utilized to increase glycemia?
Glucagon, epinephrine, cortisol, and growth hormone
What is the incretin effect?
Orally administered glucose CHO, is the primary stimulus for insulin secretion
Where does insulin go first when secreted?
Liver
Basal Release is what?
Continuously secreted insulin from the pancreas
Bolus Release is broken into what?
First Phase and Second Phase
First Phase Bolus is:
Peak in insulin secretion in response to meals, shuts down hepatic glucose production
Second Phase Bolus is:
delayed, mostly used in periphery
What is the key action of insulin?
Insulin promotes glucose uptake, without it there is no glucose uptake
What are the 3 general actions of insulin?
Lowering of blood glucose, promotes storage of glucose, and promotes potassium intake
What are the effects of insulin in the liver?
Promote glucose uptake, stimulate glycogen storage, synthesis of triglycerides, and inhibits glycogenolysis
Insulin Action in Muscle and Adipose
Both have increase glucose uptake, muscle = AA, adipose = triglycerides
What is the major source of elimination for endogenous insulin?
Liver
What are the insulin requiring tissues?
Muscle and Adipose
What is GLP-1?
Glucagon Like Peptide that is released by L-cells in the intestine in response to glucose
What is the action of GLP-1?
Stimulates insulin secretion (glucose dependent)
How is GLP-1 metabolized?
Rapidly by DPP-4 (dipeptidyl peptidase 4)
What is GIP?
Glucose Dependent Insulinotropic Peptide, released from K cells in response to glucose/fat intake
What is the action of GIP?
Promote insulin biosynthesis, insulin secretion (glucose dependent)
How is GIP metabolized?
Rapidly by DPP-4
What is the role of Amylin?
Promotes lowering of glucose by: slow gastric empty, suppression of glucagon, increase satiety
When are GLP-1 and GIP released?
As you eat/glucose consumption
What are glucose levels in an normal prior to a meal?
70-99
What should glycemic levels be maintained at?
Fasting: less than 100
After Glycemic Load: Less than 140
What happens during a meal?
- GLP-1 and GIP
- First Phase
- Second Phase
- Decrease in Counter Regulatory Hormones
What are the counter regulatory hormones to insulin?
Glucagon, epinephrine, cortisol, and growth hormone
Glucagon secreted from pancreatic alpha cells has what action?
Primary effect on the liver to stimulate glycogenolysis and gluconeogenesis
In the presence of what is glucagon inhibited?
Glucose
What is the role of Epinephrine?
Stimulates hepatic glucose release via glyconeolysis and lipolysis
What is the role of Cortisol?
Stimulates hepatic uptake of AA which can be used to produce glucose
What is the role of Growth Hormone?
Stimulates lipolysis and inhibits glucose uptake in muscle and adipose tissue
What happens when there is absence of insulin in the liver?
Increase glucose production, increase lipolysis and subsequent increase in ketone production
What are the 3 main ketones produced?
Beta Hydroxybutyrate, Acetoacetic Acid, and Acetone
What happens when there is a lack of insulin in Muscle and Adipose?
Muscle: protein breakdown to release AA for hepatic gluconeogenesis
Adipose: increased lipolysis to release free FA for hepatic gluconeogenesis and ketone
What is Hemoglobin A1c?
Glucose binds hemoglobin A1, molecule in a concentration dependent manner
Marker of glycemia over 2-3 month period
What is the goal A1c of a normal person?
4-5.6%
What is the goal A1c for diagnosed patient?
<7%
What is the goal fasting/preprandial BS of a normal person?
<100 mg/dL
What is the goal fasting/preprandial BS of a diagnosed patient?
80-130 mg/dL
What is the goal postprandial BS of a normal person?
<140 mg/dL
What is the goal postprandial BS of a diagnosed patient?
<180 mg/dL
What is the goal bedtime range for a diagnosed person?
100-180 mg/dL
What is the estimated correlated FSBS of an A1c of 10%?
240
If you are estimating FSBS, if you drop 1% of A1c, what is average drop in BS?
30
aka 9% = (10%) 240-30 = 210
When to monitor A1c with Diabetes?
Every 3 months when A1c not at goal
Every 6 months when at goal
Every 12 months when A1c within pre-diabetes range
Screening A1c Recommendations
Risk Factors = Anytime
Age 35 and Every 3 years if normal
Pre-Diabetes Definition
Blood glucose or A1c levels higher than normal but not high enough to be classified as diabetes
What is IFG?
Fasting plasma glucose 100-125 mg/dL
What is IGT?
OGTT result with 2 hour plasma glucose of 140-199 mg/dL
What is classification of prediabetes?
Patients who meet IFG or IGT criteria
A1c 5.7-6.4%
Diabetes Diagnostic Criteria
A1c >6.5% OR,
Fasting plasma glucose >126 mg/dL OR,
Symptoms of hyperglycemia and random plasma glucose >200 mg/dL OR,
OGTT with 2 hour plasma glucose >200 mg/dL
Which type of diabetes produce antibodies to B-cells making it an autoimmune disorder, autoantibodies that begin to destroy B-Cells?
Type 1
What are the types of antibodies?
Glutamic Acid Decarboxylase 65 GAD65
Islet Cell Antibody ICA
Insulin Autoantibody IAA
Tyrosine Phosphatases Antibody IA-2
What is the pathogenesis of Type 2 DM?
Early resistance to insulin resulting in pancreas compensating with hyperinsulinemia, but normal glycemia
Impaired glucose tolerance IGT
Impaired fasting tolerance IFT
Diagnosis of Metabolic Syndrome (3 out of 5 required)
Abdominal Obesity (>40 M, >35 W)
Elevated triglycerides >150
Elevated BP >130/85 or on medication
Elevated fasting glucose >110
Low HDL <40 M, <50 W
What are the implications of metabolic syndrome?
Inflammation, diabetic dyslipidemia, prothrombotic state, endothelial dysfunction/vascular, and increased risk for CV disease
What is GAD and what does it indicate?
Glutamic Acid Decarboxylase Antibody GAD, may indicate LADA aka Type 1 and 1/2
What are the laboratory markers of Type 1?
Low serum insulin, Low C-Peptide, Present autoantibodies, High blood glucose, Present glycosuria, High A1c, and Present ketones
What are the risk factors for Type 2 DM?
BMI >25 or >23 in Asian Americans, history or impaired glucose tolerance, physical inactivity, family history of diabetes, high risk ethnicity, history of gestational diabetes, HTN, low HDL, triglycerides >250, polycystic ovary disease, other conditions associated w/insulin resistance, history of CV disease, and metabolic syndrome
What are the laboratory markers of Type 2 DM?
Normal/Elevated serum insulin and C-Peptide, Absent autoantibodies, Elevated glycemia, Elevated A1c, Present glucosuria, Uncommon ketones, and Hyperglycemia hypersomolar syndrome
What is DKA?
Diabetic Ketoacidosis, Type 1 Exacerbation
What are S/S of DKA?
Abdominal pain, fruity breath, CNS depression, coma, tachycardia, dehydration, and tachypnea
What is HHS?
Hyperglycemic Hyperosmolar State, Type 2 Exacerbation, NO ketones
What are the S/S of HHS?
Hyperglycemia >1000 mg/dL, lethargy, confusion, hypotension, and tachycardia
What are the causes of hyperglycemia?
Associated with suboptimal medication, excessive glucose release from the liver, excessive ingestion of CHO, and medications (steroids)
What are symptoms of hyperglycemia?
Polyuria, serum glucose >180
Polyphagia
Polydipsia
What are the causes of hypoglycemia?
Excessive quantity of medication, more than usual physical activity, and inadequate food intake
What are the symptoms of hypoglycemia?
Autonomic: trembling, pounding heart, tachycardia, sweating
Neuroglycopenic: blurred vision, slurred speech, numbness, dizziness
Other: hunger, nausea, weakness, headache
What is released resulting in most of the autonomic symptoms?
Epinephrine
What is the treatment for mild hypoglycemia?
Consume 15-20 g of simple CHO
Recheck BS in 15-20 mins
Repeat treatment if necessary
What do you administer during severe hypoglycemia, unresponsive?
Glucagon
What are the risks for Gestational Diabetes GDM?
Macrosomia, excessive maternal weight gain >40 lbs, preeclampsia, still birth, neonatal hypoglycemia, hyperbilirubinemia, hypocalcemia, respiratory distress syndrome,
Increased risk of baby developing DM2, obesity, or metabolic syndrome
Increased risk of maternal development of DM2