Diabetes: Lecture 1 Flashcards
What is glucose stored as? and where?
Glycogen
Skeletal Muscle and Liver
Hormones that control Blood Glucose?
Pancreatic
Counter-regulatory
Gut-Derived
Which cells secrete Glucagon?
Alpha Cells
What does Glucagon do?
effect breakdown of liver glycogen and increase glucose levels in the blood
Which cells secrete Insulin & Amylin?
Beta cells
Where are Alpha and Beta Cells located?
Pancreatic Islet of Langerhorn
What does Insulin do?
Increase uptake of glucose into cells and facilitate conversion of glucose to glycogen in the liver
What does Amylin do?
suppress digestive secretions
Slows gastric emptying
What increases Glucagon release?
by increased glucose levels and presence of fatty acids and ketones
What stimulates glucagon release?
decreased glucose levels and presence of amino acids
List of counter-regulatory hormones?
Glucagon
Epinephrine
Growth Hormone
Cortisol
“Fed State” process
Increased glucose stimulates B cells to release insulin
Insulin stimulates glucose uptake by cells and glycogenesis in liver
Plasma levels return to normal
“Fasting state” process
Decrease glucose stimulates A cells to release glucagon
Glucagon stimulates gluconeogenesis and glycogenolysis in liver and release of glucose to plasma
Plasma glucose levels return to normal
“Lock and Key” Analogy glucose
Insulin acts as “Key” so glucose can get into cell “Through door”
What releases GLP-1?
L cells of ileum and Colon
What releases GIP?
K cells of duodenum
What are glucose dependent hormones?
Only secreted in response to oral ingestion of food
GLP-1 and GIP, so levels low when glucose low
What does GIP do?
act on B cell
Insulin sensitizer in adipocytes
No effect on glucagon secretion, gastric motility or satiety
What does GLP-1 do?
Act on A & B cells?
Suppress glucagon secretion
Slows gastric emptying and increase satiety
GLP-1 and GIP Half life?
~10 min
Inactivated by Dipeptidyl Peptidase-4 Enzyme (DPP-4)
Role of Kidney in Glucose Regulation?
- release of glucose via gluconeogenesis
- uptake of glucose from circulation
- Kidney reabsorbs glucose
90% by SGLT-2
10% by SGLT-1
Diabetes definition
Chronic and progressive metabolic disorder characterized by abnormalities in the ability to metabolize carbohydrate, fat, and protein, leading to a hyperglycemic state
Type 1 Diabetes Classification
autoimmune B-cell destruction, usually leading to absolute insulin deficiency
Type 2 Diabetes Classification
progressive loss of B-cell insulin secretion frequently on the background of insulin resistance
Gestational diabetes Classification
diabetes that is first diagnosed in the 2nd or 3rd trimester that is not clearly preexisting type 1 or 2 diabetes
Possible causes of diabetes?
genetic defects
Disease of the exocrine pancreas
Drug induced Hyperglycemia
Type 1 Diabetes cycle
- Pancreas doesn’t make insulin
- Decreased insulin in blood vessels
- Increased glucose due to low insulin
- Muscle unable to use glucose due to low insulin
Glycogen and protein breakdown, causing keto-acidosis
Stages of Type 1 diabetes?
Stages 1 - Stage 3
Stage 1 of Type 1
Autoimmune
Normoglycemic
Presymptomatic
Stage 2 of Type 1
Autoimmune
Dysglycemic
Presymptomatic
Stage 3 of Type 1
Autoimmune
Hyperglycemic
Symptomatic
Type 1 Diabetes Rate of Progression depends on….
Age at first detection of autoantibody
# of autoantibodies
Autoantibody specificity
Autoantibody titers
Insulin resistance
Inability of peripheral tissues to respond properly to insulin.
Get insulin resistance at muscle, liver, adipocytes
“Core Defects” of Type 2 diabetes?
Insulin Resistance and B-cell failure
(T2DM Defects) Impaired Insulin Secretion
B-cells of pancreas cant make enough insulin
(T2DM Defects) Inefficient glucose uptake in muscle
“Lock and Key” Insulin needed to “open” cell to let glucose in
(T2DM Defects) Insulin resistance in liver
Leads to overproduction of glucose
Especially overnight when sleeping
(T2DM Defects) Insulin resistance at fat cell
Fat cell becomes resistant and starts to breakdown triglycerides, leads to release of free fatty acids
(T2DM Defects) Alpha cell of pancreas
supposed to turn off glucagon production.
This is signaling is “Off”
(T2DM Defects) Decreased Incretin effect
resistance to incretin hormones
contributes to impaired insulin and excessive glucagon secretion
(T2DM Defects) Increased Glucose Reabsorption
Kidney reabsorbs a bunch more glucose cause have so much. Leads to glucose staying in the blood stream.
(T2DM Defects) Neurotransmitter dysfunction
Related to appetite suppression, contributes to feeling of fullness.
System isn’t working.
How many total defects with (T2DM Defects)
8
“Ominous Octet’
% Loss of beta cell function at diagnosis?
~ 50%
Type 1 Summary
Defect in pancreatic B-cell function
Absolute insulin deficiency
Type 2 Summary
Insulin resistance involving muscle, liver and adipocytes
Defects in insulin secretion
GLP-1 deficiency and resistance
Excess glucagon secretion
Reabsorption of glucose by the kidney
Defects in signaling to the brain
Type 1 Risk factors
Genetics
Environmental (Poorly defined)
Type 2 Risk factors
Obesity (weight circumference in asians) Physical inactivity Hypertension Abnormalities in Cholesterol HTN FMH Women w/ GDM AA,Latino, Asian, Native, Pacific Islanders CVD
Acanthosis Nigricans
Skin issue that shows insulin resistance
% of pop that is Type 1 Diabetes?
5-10%
% of pop that is Type 2 Diabetes?
up to 90%
Difference vs Type 1 and Type 2 onset?
1 is abrupt
2 is usually gradual
Symptoms common with Type 1 Diabetes?
3 P’s
Poluria, polydipsia, polyphagia
unexplained weight loss
Symptoms common with Type 2 Diabetes?
Fatigue, poor wound healing, polyuria, polydipsia, nocturia
Risk factors for Gestational Diabetes?
Overweight/Obese
Older age >30
FMH of Type 2
Pathophysiology Gestational Diabetes
insulin resistance
Diminished insulin secretory response
Riks to mother and baby from Gestational Diabetes
Macrosmia Shoulder dystocia Preeclampsia Cesarean delivery Stillbirth
Clinical Manifestations of Hyperglycemia
Fungal and microorganism growth
Osmotic diuresis
Depletion of carb stores/ poor use of food products
Things that decrease glucose
insulin
Excess DM meds
increased exercise
Alcohol
Things that increase glucose
Counter-regulatory hormones Insufficient DM Meds Other meds (Gluccocorticoids, Clozapine, Olanzipine)*** Excess Food Illness Stress
Drugs that increase glucose that are clinically relevant?
Gluccocorticoids
Clozapine
Olanzipine
Autoantibodies you would check for in Type 1 diabetes?
Islet cell (ICA)*** Glutamic Acid decarboxylase (GAD65)*** Insulin autoantibodies (IAA) Tyrosine phosphates (IA-2 and IA-2B) Zinc Transporter 8 (ZnT8)
*** = Most common
Screening for Type 2 Diabetes
Start age 35 all patients
Adults any age BMI >25/23 Asians plus 1 or more risk factor
ppl with HIV, prediabetes
women with GDM
Consider fat kids with 1 or more diabetes risk factor
If Type 2 diabetes screening results are normal then….
can repeat every 3 years
If Type 2 diabetes screening results indicate pre-diabetes then….
repeat yearly
Tests used for both screening and diagnosing of diabetes?
Fasting plasma glucose (FPG)
Casual plasma glucose
2h plasma glucose during oral glucose tolerance test (OGTT)
Hemoglobin A1C
When is OGTT often used?
In pregnant women
Limitations of A1C test
conditions that alter red blood cell turnover
Sickle Cell
Pregnancy
etc.
A1C levels
Prediabetes: 5.7-6.4%
Diabetes: >6.5%
FPG levels
Prediabetes: 100-125 mg/dL
Impaired fasting glucose
Diabetes: >126 mg/dL
OGTT levels
Prediabetes: 140-199 mg/dL
Impaired glucose tolerance
Diabetes: >200mg/dL
Random glucose levels
> 200mg plus classic symptoms of hyperglycemia or hyperglycemic crisis
Goals for Type 1 and Type 2 Diabetes?
A1C < 7%
preprandial glucose 80-130 mg/dL
Peak postprandial glucose <180
Pediatrics Type 1 Diabetes goals?
A1C: <7.5%
Preprandial glucose: 90-130mg/dL
Bedtime/overnight: 90-150 mg/dL
Is A1C accurate in pregnant women?
not as accurate, would use OGTT to assess
Target range of glucose for hospitalized patients?
target range 140-180 mg/dL
Wen adjusting A1C goal, don’t want to greater than….
8.5%
Older adult goals: Healthy
A1C: <7-7.5%
Preprandial glucose: 80-130mg/dL
Betime glucose: 80-180mg/dL
Older adult goals: Complex/Intermediate
A1C: <8%
Preprandial glucose: 90-150 mg/dL
Bedtime glucose: 100-180mg/dL
Older adult goals: Very Complex/poor health
A1C: <8.5%
Preprandial glucose: 100-180 mg/dL
Bedtime glucose: 110-220 mg/dL
Rational between Health statuses?
Life expectancy
