30 Diabetes Mellitus Flashcards
Classification of Diabetes Mellitus (DM)
Type I
- ? destruction usually leading to ? deficiency
- Cause?
Type II
- ? resistance with partial to complete ?
- Cause?
Others:
?
Disease of ? (eg cystic fibrosis and pancreatitis)
Type I
- Pancreatic beta cell destruction usually leading to insulin deficiency
- Autoimmune causes triggered by environmental factors in genetically prone people
Type II
- Insulin resistance with partial to complete insulin deficiency
- Complex interplay between environmental causes and genetics
Others:
Gestational diabetes
Disease of exocrine pancreas (eg cystic fibrosis and pancreatitis)
Pancreas
Which cells secrete what?
Alpha cells -> ?
Beta cells -> ?
Which cells secrete what?
Alpha cells -> glucagon
Beta cells -> insulin
Glucose Regulation
Insulin vs Glucagon
Fed State:
- 5
Fasting state
- 5
Insulin vs Glucagon
Fed State: glucose is absorbed from our gut into the bloodstream, raising blood glucose levels -> causes insulin to be released from the pancreas:
- Glucose uptake into cells
- Glucose utilization (Glycolysis)
- Glucose storage as glycogen (glycogenesis)
- Fat synthesis (lipogenesis)
- Protein synthesis
Fasting state: Glucagon is secreted in response to hypoglycemia, prolonged fasting, exercise and protein-rich meals
- Glucose synthesis (gluconeogenesis)
- Glycogen b/d (glycogenolysis)
- Fat b/d (lipolysis & beta-oxidation)
- Protein b/d (proteolysis)
- Formation of ketone bodies (ketogenesis)
Insulin actions
Insulin release from pancreatic ? cells is triggered by ?
Insulin acts on:
1)Liver:
- ↑ 3
- ↓ 2
2)Adipose tissue:
- ↓ 1
- ↑ 2
3)Striated mm
- ↑ 3
Insulin release from pancreatic beta cells is triggered by Glucose
Insulin acts on:
1)Liver:
- ↑ Glycogen synthesis
- ↑ Lipid accumulation/Lipogenesis
- ↑ Inflammation
- ↓ Gluconeogenesis // Ketogenesis
2)Adipose tissue:
- ↓ Lipolysis
- ↑ Glucose uptake/metabolism // Lipogenesis
3)Striated mm
- ↑ Glucose uptake/metabolism // Glycogen synthesis // protein synthesis
Ketogenesis (brain fuel)
- Ketones are an alternative fuel source for the ? when ? is unavailable
- Lack of ? or its actions on tissue (ie diabetes) or lack of ? (ie starvation) leads to increased ? and release of Fatty acids from ? tissue
- Fatty acids will be metabolized in liver through ? into ? intermediates
- When rate of beta-oxidation increases ? bodies are produced // these are ? and include beta-hydroxybutyrate and acetoacetate → ?
- Ketones are an alternative fuel source for the brain when glucose is unavailable
- Lack of insulin or its actions on tissue (ie diabetes) or lack of glucose (ie starvation) leads to increased lipolysis and release of fatty acids from adipose tissue
- Fatty acids will be metabolized in liver through beta-oxidation into acetyl CoA intermediates
- When rate of beta-oxidation increases ketone bodies are produced // these are acidic and include beta-hydroxybutyrate and acetoacetate → ketoacidosis
Ketogenesis occurs primarily in the mitochondria of liver cells
Effects of hyperglycemia in the body (T2DM)
Molecular mechanisms:
- overproduction of ? by mitochondrial ETC
- Leads to formation of ?, ? and ?
- Altered ? function, ? and ?
Cellular and tissue damage:
- Damage to ?
- Reduced ? and ? nerve conduction
- Increased permeability of ? from kidney
- Osmotic effects: ? and ?
- Depression of ? system = increased risk of infections
Molecular mechanisms:
- overproduction of superoxide by mitochondrial ETC
- Leads to formation of reactive oxygen species, cytokines and growth factors
- Altered protein function, gene expression and signal transduction
Cellular and tissue damage:
- Damage to blood vessels
- Reduced sensory and motor nerve conduction
- Increased permeability of proteins from kidney
- Osmotic effects: polyuria and dehydration
- Depression of immune system = increased risk of infections
Insulin resistance T2DM
- Insulin ? and ? defects
- Decreased uptake of ? by insulin sensitive tissues (3)
- Increased ? production and release of ? (?)
Increase ? in adipose
- maldistribution of ?
- Increased circulating ? → ? damage
- Insulin receptor and signaling defects
- Decreased uptake of glucose by insulin sensitive tissues (mm, adipose, liver)
- Increased hepatic production and release of glucose (gluconeogenesis)
Increase lipolysis in adipose
- maldistribution of fat
- Increased circulating free fatty acids → liver damage
Acute Complications DM
- ? state (HSS) occurs in type II diabetes
- Triggerd by ?
- No ? due to residual insulin availability
- Treatment: 3
- Hyperosmolar hyperglycemic state (HSS) occurs in type II diabetes
- Triggerd by other illness (infection // renal failure // stroke // heart attack
- No ketogenesis due to residual insulin availability
- Treatment: Rehydration // correction of electrolytes // insulin therapy
Screening and Diagnosis T2DM
Screening and diagnosis T2DM
(3)
- Fasting or Random plasma glucose
- Hemoglobin A1c (HbA1c)
- Suppression testing - 75g oral glucose tolerance test (OGGT)
HbA1c:
- glycated form of hemoglobin in RBCs that is irreversibly bound to glucose due to prolonged exposure (glycation)
- Half life of RBC ~3months therefore HbA1c is a marker of long-term glucose control
- Lower HbA1c (ie tighter glycemic control) in diabetic patients linked to reduction in microvascular and macrovascular complications
Hemoglobin(Hb)A1c screening for DM
HbA1c:
- glycated form of ? in RBCs that is irreversibly bound to ? due to prolonged exposure (?)
- Half life of RBC ~?months therefore HbA1c is a marker of ?
- Lower HbA1c (ie tighter ? control) in diabetic patients linked to reduction in ? and ? complications
HbA1c:
- glycated form of hemoglobin in RBCs that is irreversibly bound to glucose due to prolonged exposure (glycation)
- Half life of RBC ~3months therefore HbA1c is a marker of long-term glucose control
- Lower HbA1c (ie tighter glycemic control) in diabetic patients linked to reduction in microvascular and macrovascular complications
HbA1c targets are used to reduce complications
Non-pharmacologic:
- diet/weight management //
- exercise and smoking cessation
Pharmacologic:
- Oral antihyperglycemic agents (ie metformin)
- Insulin
TIIDM
HbA1c targets are used to ?
Non-pharmacologic:
- ?
- ?
Pharmacologic:
- Oral ? agents (ie ?)
- ?
HbA1c targets are used to reduce complications
Non-pharmacologic:
- diet/weight management
- exercise and smoking cessation
Pharmacologic:
- Oral antihyperglycemic agents (ie metformin)
- Insulin
Acute Complications T1DM
- Diabetic ? (DKA) is mostly found in T1DM due to lack of ? (emergency)
Clinical features:
- ?
- ?
- ?
- ?
- ?
- ?
- ?
- ? (?)
Treatment:
- ?
- ?
- correction of ? and ? balance
- Diabetic ketoacidosis (DKA) is mostly found in T1DM due to lack of insulin availability (emergency)
Clinical features:
- polyuria
- fatigue
- Nausea
- Vomiting
- abnormal pain
- dehydration
- confusion
- loss of consciousness (cerebral edema)
Treatment:
- rehydration
- insulin therapy
- correction of acid/base and electrolyte balance
Screening and Diagnosis T1DM
How to screen for T1DM?
Diagnosing T1DM:
How to screen for T1DM?
-No screening recommendations
Diagnosing T1DM:
- Same criteria as T2DM: HbA1c, fasting/random glucose, OGTT
- Autoantibodies
- Insulin precursor: C-peptide
Autoantibodies and insulin precursor have questional diagnostic accuracy but may help differentiate type 1 from 2 in certain scenarious
- Fasting or Random plasma glucose
- Hemoglobin A1c (HbA1c)
- Suppression testing - 75g oral glucose tolerance test (OGGT)
Which of the following is correct about glucose metabolism?
a) Insulin raises blood glucose levels while glucagon lowers levels
b) Transport of glucose into cells occurs through passive diffusion
c) Ketogenesis occurs in the liver via beta oxidation
d) One role of insulin is to stimulate beta oxidation in the muscle
a) insulin lowers blood glucose while glucagon increases glucose
b) Transport of glucose into cells occurs through GLUT transporters
c) Ketogenesis occurs primarily in the mitochondria of liver cells via beta-oxidation
d) insulin decreases beta-oxidation
Diagnosis of type II diabetes involves what test(s)?
a) HbA1c
b) Insulin autoantibodies
c) Oral glucose tolerance test
d) C-peptide
e) A or C
Diagnosis of type II diabetes involves what test(s)?
a) HbA1c
b) Insulin autoantibodies
c) Oral glucose tolerance test
d) C-peptide
e) A or C
Insulin autoantibodies and d) C-peptide (insulin precursor) indicate Type 1 diabetes vs Type 2
