Endocrine Patho - Diabetes Mellitus

Question 1

What can diabetes lead to?

Answer 1

Cardiovascular disease, stroke, blindness, chronic kidney disease, amputation, and premature death

Question 2

What happens in glucose metabolism?

Answer 2

Body uses glucose, fatty acids, etc. for energy
Glucose: exclusive energy source for the brain, nerves, RBC
Blood transports glucose after meals
Some stored in liver as glycogen; released between meals
Liver & hormones control body’s fuel supply
Extra glucose stored as fat
Liver also can perform gluconeogenesis

Question 3

What does the pancreas do?

Answer 3

Exocrine pancreas
secretes digestive enzymes & juices (Acini)
Endocrine pancreas 
hormonal control of blood sugar
Islets of Langerhans secrete hormones
Beta cells: insulin & amylin
Alpha cells: glucagon
Delta cells: somatostatin (gastrin)

Question 4

What does somatostain do?

Answer 4

decrease GI motility, slows transit time of food through GI tract, more constant absorption

Question 5

When is insulin released?

What do it do?

Answer 5

Insulin released as glucose rises; decreased as glucose drops
Promotes the uptake of glucose into cells
Skeletal muscle
Adipose tissue – increased fatty acid storage
Promotes storage of glucose as glycogen by liver
Prevents fat and glycogen breakdown
Inhibits gluconeogenesis, preventing protein breakdown
Increases protein synthesis

Question 6

What is involved in glucose transportation?

Answer 6

Glucose transporters (GLUT): movement of glucose into cells
Tissue specific:
For example: GLUT-4 in skeletal muscle and adipose tissue
insulin dependent glucose transporter: GLUT-4
Glut 4 – inside cell, only allow glucose in the cell when insulin is present

Glucose enters cells slowly and constantly
Major transporter in nervous system (CNS & PNS) (no insulin required)
Exercise can speed this up
So high blood glucose can be decreased by exercise through these receptors

Question 7

What is glucagon released by?

Answer 7

alpha cells

Question 8

What does glucagon do?

Answer 8

Maintains blood glucose between meals – main effect is to ↑ blood glucose
glycogenolysis  and gluconeogenesis
Secretion of glucagon stimulated by
low blood glucose levels
Strenuous Exercise
Stress Response
Opposite of what stimulates insulin

Question 9

When is glucagon released?

Answer 9

Release when glucose is almost gone in blood

During strenuous exercise and stress glucagon goes up and insulin goes down

Question 10

By what is amylin released and what does it do?

Answer 10

Natural substance released by Beta cells of pancreas with insulin
Delays gastric emptying
Suppresses glucagon secretion which would cause gluconeogenesis and glycogenolysis
Increases sensation of satiety (decreases appetite)

Question 11

What does epinephrin do?

Answer 11

helps maintain blood glucose during physiological stress

Question 12

what does growth hormone increase?

Answer 12

protein, which synthesizes and mobilizes fatty acids and inhibits insulin

Question 13

glucocorticoid hormones

Answer 13

stimulate gluconeogenesis, glucose levels increase during stress

Question 14

what occurs in diabetes mellitus?

Answer 14

Group of diseases
Chronic Hyperglycemia (fasting, haven’t eaten in 8 hrs, blood glucose level >125mg/dL)
Features: disturbances of carbohydrate, protein and fat metabolism (metabolism of everything)
Imbalance between cellular need for insulin and availability
Factors include insulin secretion, insulin utilization, and glucose production

Question 15

What is the difference between types of diabetes?

Type 1, type 2, gestational diabetes, diabetes secondary to other conditions, pre-diabetes

Answer 15

Type 1: absolute lack of insulin
Type 2: insulin present but receptor resistance and/or secretion problems
Gestational diabetes, diabetes during pregnancy
Pre-term birth, high birth weight, moms have a higher chance of developing type 2
Diabetes secondary to other conditions
tumors
Pre-diabetes
Impaired glucose tolerance (IGT), gave 75gram of glucose but body didn’t release glucose to increase % in blood
Impaired fasting glucose (IFG)

Question 16

How would you diagnose diabetes?

Answer 16

Classic Sx of polyuria (large amounts of urine output), polydipsia (drinking a lot, thirsty), polyphagia, blurred vision, or candida infections WITH
Random/casual blood glucose > 200 mg/dL
Hb A1C > 6.5 %
% of A1C hemoglobin with glucose attached
Indicates average glucose in past 2-3 months

Need both signs and ^ glucose to diagnose

Signs - ^ blood osmolality
Fasting plasma glucose (FPG) of > 126 mg/ dl (after 8 hour fast)
2 hr. oral glucose tolerance test (OGTT) with excess of >200 mg/dl (75 gms glucose)

Question 17

Type 1 Diabetes

Answer 17

Destruction of beta cells that release insulin
Only 10% of diabetes
Usually a younger age group but any age
Genetic predisposition + environmental assault
Infection (CMV, EBV, rubella, mumps) – triggers antibodies to destroy insulin
Two subtypes
1A (autoimmune) and 1B (idiopathic)

Question 18

Type 1 Autoimmune Diabetes

Answer 18

Absolute lack of insulin
Body breaks down fats
Fatty acids released that convert to ketones
Prone to ketoacidosis
Body breaks down protein
Leads to catabolic state
All require insulin replacement
Autoimmune process
95% of Type 1
Predisposition
Main susceptibility gene on chromosome 6
Autoantibodies produced to insulin and islet cells
Lymphocyte infiltration of Islets
T lymphocytes, TNF, B cell/plasma cell production
Antibodies may exist for years before beta cell destruction
Destruction of beta cells and regeneration
Onset longer than appears
symptoms may appear suddenly

Question 19

Type 1B Idiopathic

Answer 19

Beta cell destruction without antibodies
Prevalence rare
Strong genetic tendency (African / Asian descent)
Absolute insulin lack varies over time
s/s vary during initial stages of the disease
Problems
High serum glucose levels (> 126 mg/dL fasting)
Often much higher at diagnosis
Polyuria – glucose spills into urine and large amount of water excreted
Polydipsia- from increased osmolality of blood), drinking lots of water
No insulin so glucose not used by many cells
Cells must use other fuel  protein and fat breakdown
Weight loss and polyphagia, increased appetite
Ketones and ketoacidosis, decreased pH of the blood, from increased metabolism fatty acids

Question 20

Effect of High Serum Glucose Levels

Answer 20

High serum osmolality in blood
Pulls water from intracellular
Patient may show signs of dehydration
Warm, dry skin & mucous membranes, tenting
Polydipsia
High levels of glucose causes increase in osmotic pressures in kidney tubules
Decreases fluid re-absorption into blood
Excessive fluid loss through urine - Polyuria

Question 21

Effect of Excess Fatty Acid Metabolism

Answer 21

May have acidosis (pH < 7.35)
Excess fatty acids metabolized by liver into ketones (acidic)
Effects of acidosis
Deep rapid respiration (Kussmaul breathing)
compensation to reduce acidosis
fruity breath
Flushed warm skin

Question 22

Diabetic Ketoacidosis (DKA)

Answer 22

Diabetic emergency
Occurs in Type 1
Hyperglycemia
Lack of insulin
Stress induced will also have ↑ Glucagon  Gluconeogenesis & glycogenolysis
Ketoacidosis
Lack of insulin  mobilization of fatty acids  ↑ ketones and acidosis
Combination of acids (ketones) and high glucose create the signs & symptoms
Blood glucose > 250 mg/dL
Low bicarb <7.3 (ketone bodies are acid)
Hyperkalemia: K+ will leave cells if blood is high in H+ (acidic) – blood levels may be high
Danger to heart rhythm
Ketones (acids) present in urine and blood

Question 23

Signs of Diabetic Ketoacidosis

Answer 23

Confused or unconscious 
Pink, flushed, warm (vasodilation)
Nausea, vomiting, abdominal  pain
Glucose and acidosis
Heart arrhythmias
Fruity breath –trying to excrete ketoacids
Kussmaul breathing – to reduce acidosis (deep, rapid breathing)
Polyuria – loss of fluid volume – low BP
Rapid pulse – loss of fluids

Question 24

How do you manage Ketoacidosis

Answer 24

Life threatening
Provide isotonic IV fluids immediately
Provide insulin next
IV regular insulin/insulin infusion
Fast acting sq insulin
Correct electrolytes
Watch K+ because it will go back into cells hypokalemia

Question 25

Type 1 Diabetes Tx

Answer 25

``` Always needs insulin Sub q injections, continuous pump Requires glucose monitoring High risk for hyperglycemia and hypoglycemia Importance of Lifestyle Adherence to diabetic diet Good meal planning to match insulin dose Consistent exercise/activity program ```

Question 26

Type 2 diabetes Metabolic Syndrome Indicators

Answer 26

``` Need to have at least 3 of the following Abdominal obesity Waist measurement: >35” in women; >40“ in men Asians: >30” women, >35” men Dyslipidemia High triglycerides in blood > 150 mg/dl Low HDL (good cholesterol) < 40 in men, < 50 in women (good cholesterol low) BP >130/85 Fasting plasma glucose >99 mg/dl ```

Question 27

Why is obesity a great risk factor for type 2 diabetes?

Answer 27

Excess Free Fatty Acids (chronic elevation) causes Beta cell toxicity Insulin resistance in peripheral tissues and inhibits glycogen storage Increase hepatic glucose production Glycogenolysis and gluconeogenesis

Question 28

Metabolic Syndrome and Adipokines

Answer 28

Adipokines are cytokines (chemical messengers) released by adipose tissue Resistin – prevents glucose from entering cells Other are inflammatory and excess numbers contribute to development of atherosclerosis: Tumor necrosis factor (TNFα) Interleukin 6 (IL-6) C-reactive protein (CRP)

Question 29

Type 2 Diabetes Mellitus

Answer 29

Risk: Combination of genetic factors & environmental Obesity, physical inactivity, metabolic syndrome, age & genetics Multiple genes involved Unable to identify a single gene that causes disease Family history increases risk 2-4X those without family history Not autoimmune; no antibodies

Question 30

Patho of type 2 diabetes mellitus

Answer 30

Main problem is insulin resistance – poor utilization by muscles, fat, liver Insulin levels may be high, normal or low Beta cells fail trying to release more Liver increases blood glucose Insulin resistance – cells can’t use insulin Decreased response to insulin Skeletal muscle, Adipose tissue Liver: continued glucose production Abnormal secretion of insulin from beta cells Beta cells cannot respond quickly to glucose in blood stream May not make enough insulin Often too much insulin (compensatory increase)  hyperinsulinemia Increased glucagon increases glucose production by liver –glycogenolysis;gluconeogenesis

Question 31

What causes beta cell dysfunction in Type 2?

Answer 31

Hyperinsulinemia wears out beta cells Glucotoxicity- glucose induced beta cell desensitization- stop responding to high glucose in blood Amyloid deposits in pancreas reduce # of beta cells

Question 32

Clinical Manifestation of Type 2

Answer 32

Symptoms develop slowly Polyuria Polydispsia Nonspecific: fatigue, recurrent infections, visual changes, neuropathy Usually do not have polyphagia and weight loss seen in Type 1

Question 33

Treatment for Type 2 DM

Answer 33

``` Goal is euglycemia Diet - appropriate calorie, low fat, higher fiber Reduction of weight / adipose tissue to decrease insulin resistance Regular exercise Aerobic and endurance ```

Question 34

Hyperosmolar Hyperglycemic State (HHS): Emergency Problem of Type 2 DM

Answer 34

AKA Hyperosmolar, Hyperglycemic Nonketotic (HHNK) Insulin present so ketoacidosis usually does not occur Possible if beta cells are exhausted Or if there is another illness/infection Patho: severe hyperglycemia, high glucose levels >600 mg/dL Huge amount of water loss, ↑ serum osmolality Dehydration → circulatory collapse S/S: Thirst, polyuria and stroke-like symptoms: Decreased consciousness , seizures Aphasia –loss of ability to use language Hemiparesis (one sided paralysis)

Question 35

HHS Treatment

Answer 35

Isotonic IV fluids - NS Restore fluids to all compartments IV insulin (regular or rapid acting) Monitoring/replacement of electrolytes

Question 36

Summary of Life-threatening Complications of Diabetes

Answer 36

``` Diabetic ketoacidosis (DKA) in Type 1 DM Hyperosmolar hyperglycemic state (HHS), no signs of ketoacidosis, in Type 2 DM Hypoglycemia in both ```

Question 37

Hypoglycemia

Answer 37

Can occur in Type 1 or 2 diabetics as complication of insulin or oral hypolycemics Blood glucose < 60 mg/dL Causes of hypoglycemia Wrong dose of insulin or oral medication Not eating after receiving insulin or oral medication Alcohol intake Increased exercise

Question 38

Blood Glucose Levels

Answer 38

Normally 70- 99 mg/dl (fasting) Mental ability declines a bit at <65mg/dL Hypoglycemia symptoms begin at about 55 mg/dL Noticeable impairment occurs at around 40 mg/dL

Question 39

Symptoms: Vary with Level of Hypoglycemia

Answer 39

``` Neruo S/S Irritability, personality changes Headache Confusion, stupor Slurred speech Ataxia (clumsy gait) Coma ``` ``` Autonomic NS Activity Hunger Anxiety Diaphoresis/sweating Tremors ```

Question 40

How do you manage hypoglycemia?

Answer 40

``` Needs carbohydrates quickly (15-20 gms) Hypoglycemia can → brain damage If able to swallow: 3-4 ounces (100-120 ml) of orange, apple, or grape juice (may add sugar) 4-5 ounces (120-150 ml) of regular (non-diet) soda Glucose tablets If unable to swallow Glucagon IM/SQ Glucose gel 50% glucose IV 15/15 rule ```