Endocrine Disorders: Diabetes

1. food intake

2. body stores (glycogen, adipose tissue, and muscle)

Sources of glucose: [2]

Gluconeogenesis

proteins and fats getting reprocessed to make new glucose:

Glycogenolysis

Glycogen stores in the liver get broken down to make glucose

4.0-6.0 mmol/L

Normal blood glucose range:

Insulin

What is released (non-diabetic) if blood sugar increases?

1. glucagon

2. epinephrine/cortisol (HPA)

What is released (nondiabetic) if blood sugar decreases? [2]

5 minutes

Half-life of insulin

1. promotes entry of glucose into tissue cells

2. increases glucose oxidation

3. increases glycogen synthesis

4. increases fat synthesis

5. increases protein synthesis

6. suppresses gluconeogenesis

Key actions of insulin [6]

1. muscle

2. adipose tissue

Target tissues for insulin [2]

NO, but it is affected by levels of insulin

Is the liver insulin dependent?

no

Does exercising skeletal muscles require insulin?

1. brain

2. kidney

3. RBCs

4. lens of the eyes

5. intestine

organs/ cells that are not insulin dependent: [5]

1. glucose cannot diffuse into the cell

2. Insulin binds to a receptor on the cell membrane

3. triggers a second messenger system, causinig

4. GLUT4 transporter inserts into cell membrane

5. GLUT4 transports glucose into the cell

How does insulin allow glucose entry into muscles and adipose tissue?

The liver

Glucagon primarily acts where?

alpha

Cells that release glucagon

Stimulate lipolysis

Glucagon acts on adipose to:?

1. promote glycogenolysis

2. promote gluconeogenesis

3. stimulate ketogenesis

Glucagon acts on the liver to: [3]

Type 2 diabetes mellitus

Diabetes where some insulin made and released but insufficient to meet the body’s needs

Is in insulin receptors: numbers or sensitivity to insulin

Major defect in type 2 DM

Defect in pancreatic beta cell

Major defect in type 1 DM

Type 1 DM

Diabetes that must have replacement with exogenous insulin

1. auto-antibodies

2. genetic

3. virus

4. drugs

5. disease

Possible causes for Type 1 Diabetes mellitus [5]Key

1. excess body weight

2. genetics

3. metabolic syndrome

Key risk factors for type 2 diabetes: [3]

1. dysfunction of pancreatic beta cell

2. change in nuber and/or sensitivity of insulin receptors

3. associated with metabolic syndrome

Reasons for insulin resistance in Type 2 [3]

1. central abdominal density

2. dyslipidemia

3. HTN

4. elevated fasting glucose

Metabolic syndrome is characterized by: [4]

Dyslipidemia

High LDL and how HDL

Childhood and adolescence

When does metabolic syndrome develop?

CV complications

People with metabolic syndrome are at risk for what?

There is decreased ATP produced, decreased energy

What does it mean by cells starving?

1. decreased energy

2. tired

3. difficulty concentrating

S+S of cell starvation [3]

1. Increased lipolysis, glycogenolysis, and gluconeogenesis (Epi/NE)

2. Increased gluconeogenesis and lipolysis in extremeties (Cortisol)

3. Rapid weight loss but eating more

HPA S+S of cell starvation: [3]

osmotic pressure of glucose causes fluid to shift from IV to IC

Fluid shift due to hyperglycemia

1. poor skin turgor

2. dry skin

3. dry mucous membranes

4. confusion

S+S of fluid shift from hyperglycemia: [4]

Kidney increases excretion of fluid to get rid of excess glucose

What do kidneys do in result of hyperglycemia?

1. polyuria

2. glucosuria

Kidney S+S of hyperglycemia: [2]

polyuria

Frequent urination

Glucosuria

high glucose in urine

Polydipsia

Thirsty, drinking a lot

Thirst centre gets stimulated by hypovolemia and hyperosmolarity

Why does hyperglycemia cause polydipsia?

1. slower onset

2. weight loss is more gradual

3. no ketosis

Key differences of Type 2 diabetes from type 1 [3]

Differences are due to the availability of some insulin, not getting as dramatic signs and symptoms and don’t see prescriptions as quickly

Why are there different signs and symptoms of Type 1 vs. type 2?

1. Diabetic keotacidosis (type 1)

2. Hyperglycemic hyperosmotic non-ketotic syndrome (type 2)

Acute complications of diabetes [2]

If therapy is ineffective then high blood glucose persists. Patient will develop complications.

Why can people develop chronic complications of diabetes?

HbA1C

Glycosylated hemoglobin. The amount of glucose the cell has been exposed to over 120 days.

1. retinopathy

2. atherosclerosis

3. nephropathy

Glycosylation of capillary basement membrane damage to blood vessels manifests as: [3]

<6.0%

Normal HbA1C in nondiabetic

<7.0%

Goal for HbA1C in diabetic

Hb + Gluc = HbA1C

formula for HbA1C:

Polyol pathway

Non-insulin using cells metabolize glucose via this pathway:

1. sorbitol

2. fructose

The polyol pathway produces this as end products: [2]

1. damage ion pumps

2. attracts water (hyperosmolar)

3. water flows into eye lens and nerves

Sorbitol and fructose (results of polyol pathway) can cause: [3]

1. cataracts (lens thickening)

2. peripheral neuropathy (nerve damage)

Biproducts of the polyol pathway can lead to which clinical manifestations?[2]

Cataracts

lens thickening

Allows for a rapid growth of germs

How can a “sweet” environment increase risk for infection?

1. poor healing of skin

2. neuropathy

3. decreased WBC and RBCs

4. Altered WBC function (glycosylation)

Reduced defenses against germs in diabetics include:(4)

Dry skin and decreased skin barrier

Why might diabetics have poor skin healing?

May not feel an injury

How can diabetic neuropathy increase the risk of infection?

Diabetic ketoacidosis

metabolic acidosis due to excess ketones in the blood

Ketones

Are produced from rapid fat/muscle breakdown

1. signs and symptoms of metabolic acidosis

2. high blood glucose

3. Arterial blood gasses

diagnosis of DKA includes: [3]

1. give insulin

2. give fluids and oxygen

treatment for DKA [2]

No ketones produced.

Why don’t type 2s get DKA?

Hyperosmolar hyperglycemic non-ketotic syndrome (HHNKS)

Same as DKA but no ketones produced. Can have higher blood glucose levels than DKA and more severe hypovolemia

1. S+S of hyperglycemia

2. glucose in urine

Cues to get a blood test: [2]

1. <7mmol/L fasting

2. impaired glucose tolerance

Diabetes can be diagnosed if blood sugar is:

levels 2h after 75g of glucose are >11.1mmol/L

OR

Random BG is >11.1mmol/L combined with excessive hunger, urine, and thirst

Impaired glucose tolerance is defined as:

Keep glucose as close to normal as possible without seriousl comprimising quality of life

Ultimate goal of diabetes management:

5-10 (as opposed to 5-8)

Goal of diabetic blood sugar 2h after a meal:

1. medications

2. diet

3. exercise

3 methods of diabetes management:

insulin is inactivated by digestive enzymes

Why is insulin given subcutaneously?

it mimics secretion of the body and helps to meet actual needs (dosing is individualized)

Why is insulin for type 1 given several tims per day and/or by actual blood glucose levels?

may help restore some lost sensitivity of insulin receptors

How can weight loss help treat type2?

Reducing calorie intake means available insulin may be sufficient

How can diet control help treat type 2?

Oral hypoglycemic agents

Drugs that increase the release of available insulin from beta cells, improves number or sensitivity to insulin receptors, and delays carbohydrate digestion and absorption

it does not actually increase insulin production, just increases the release of insulin that is already produced.

Why can’t type 1 be given oral hypoglycemic agent?

1. headache

2. hunger

3. HPA symptoms

S+S of hypoglycemia: [3]

The body cant get rid of excess insulin

Why is hypoglycemia problematic if taking exogenous insulin?

Give carbs AND protein

Tx for hypoglycemia:

Dawn phenomenon

Early rise in glucose between 2am and 8am

Somogyi effect

The body’s reaction to hypoglycemia by having a rebound hyperglycemia

1. polyuria

2. polydipsia

3. hypovolemia

Clinical manifestations of diabetes insipidus: [3]

A defect in the production of ADH in the hypothalamus or a release of ADH from the posterior pituitary or the kidneys in reacting to ADH

Diabetes insipidus etiology: