Diabetes Mellitus

Blood Glucose
(normal serum level 65 – 105 mg)

• Inside CNS
– Brain uses glucose as primary fuel
– Brain cannot store/produce glucose

• Outside CNS
– Fatty acids: stored as
• Glycogen (liver/muscles)
• Triglycerides (fat cells)
 Blood glucose, cont.
• Outside CNS, continued
– Endocrine portion of pancreas: Islets of
Langerhans
• Alpha cells make glucagon
– “counterregulatory”, acts opposite of insulin

• Beta cells make insulin

– Allows body cells to store and use carbohydrate, fats, and
protein
 DEFINITION
• An endocrine disorder in which there is
insufficient amount or lack of insulin secretion
to metabolize carbohydrates.

• It is characterized by hyperglycemia,
glycosuria and ketonuria.
 Hyperglycemia
• When blood glucose becomes high
– INSULIN allows glucose to enter cells
• Liver
– Production /storage of glycogen
– Inhibits glycogen breakdown
– Increased protein & fat synthesis (VLDL formation)
• Muscles
– Promotes protein and glycogen synthesis
• Fat cells
– Promotes storage of triglycerides
 Hyperglycemia

• Drowsy
• Flushed
• Thirsty
 Hypoglycemia
• Glucagon: causes release of glucose from liver
– “glycogenolysis (breakdown of glycogen to
glucose)
– “glyconeogenesis of glucose not available
• Lipolysis (breakdown of fat)
• Proteolysis (breakdown of amino acids)
 Hypoglycemia

• Weak, sweaty
• Confused/irritable/
disoriented
 Diabetes Mellitus
(problem with glucose metabolism)
• Major health problem worldwide
• Complications
– Blindness
– Renal failure
– Amputations
– [heart attacks and strokes]
– [OB/neonatal complications]
 Diabetes Mellitus

The good news:

– Blood glucose control reduces complications of
Diabetes!
 Diabetes Mellitus
• Absence (or ineffectiveness of ) insulin
• Cellular resistance
• Cells can’t use glucose for energy
– Starvation mode
• Compensatory breakdown of body fat/protein
• Ketone bodies from faulty fat breakdown
» Metabolic acidosis, compensatory breathing (Kussmal’s
breathing)
 Diabetes Mellitus
• HYPERGLYCEMIA: fluid/electrolyte
imbalance.
– Polyuria
• Sodium, chloride, potassium excreted
– Polydipsia from dehydration
– Polyphagia: cells are starving, so person feels
hungry despite eating huge amounts of food.
Starvation state remains until insulin is available.
 Diabetes Mellitus
• Complications of chronic hyperglycemia
– Macrovascular complications
• Cardiovascular disease (heart attack)
• Cerebrovascular disease (strokes)

– Microvascular
• Blindness (retinal proliferation, macular degeneration)
• Amputations
• Diabetic neuropathy (diffuse, generalized, or focal)
• Erectile dysfunction
 How to Avoid Complications
• Control weight
• Eat a healthy well-balanced diet.
• Get regular exercise
• Have regular checkups
• Check feet everyday for cuts and blisters
• Do not smoke!
 How to Avoid Complications
• Keep blood sugars normal
• Avoid the 2 common diabetic problems,
hypoglycemia and hyperglycemia
 Diabetes Mellitus
Types
• Type 1 - IDDM • Type 2 - NIDDM
– little to no insulin – some insulin produced
produced – 90% hereditary
– 20-30% hereditary • Other types include Secondary
Diabetes :
– Ketoacidosis – Genetic defect beta cell or
insulin
– Disease of exocrine pancreas
– Drug or chemical induced
• Gestational – Infections-pancreatitits
– Others-steroids,
– overweight; risk for
Type 2
 Classifying Diabetes Mellitus

• Type I Diabetes: autoimmune

– Beta cell destruction in genetically susceptible
person

– Some viral infections

 Classifying Diabetes Mellitus

• Type II Diabetes
– Reduction in ability of most cells to respond to
insulin
– Poor control of liver glucose output
– Decreased beta-cell function (eventual failure)
 Diabetes Mellitus
• Major risk factors
– Family history
– Obesity
– Origin (Afro-American, Hispanic, Native
American, Asians)
– Age (older than 45)
– History of gestational diabetes
– High cholesterol
– Hypertension
 Hemoglobin A1c
• A good indicator of blood glucose control.
• Gives a % that indicates control over the
preceding 2-3 months.
• Performed 2 times a year.
• A hemoglobin of 6% indicates good control
and level >8% indicates action is needed.
 Diabetes Mellitus
• Prevention of effects: combination approach
– Increased exercise
• Decreases need for insulin

– Reduce calorie intake

• Improves insulin sensitivity

– Weight reduction
• Improves insulin action
Triad of Treatment

• Diet
• Exercise
• Medication
– Oral hypoglycemics
– Insulins
 Diabetes treatment

• Diet
– Lower calorie
– Fewer foods of “high glycemic index”
– Spread meals evenly
 Dietary Guidelines
• Eat a diet low in saturated and total fat.
• Eat a diet moderate in sodium and sugar.
• Eat 5 or more fruits and vegetables a day.
• Choose a diet rich in whole grains.
 Dietary Guidelines
• Eat at the same time everyday , at least within
1 hour of regular time.
• Eat about the same amount of carbohydrate
with each meal.
 Diabetes treatment

• Exercise
– Under physician supervision
– Check glucose prior
 Diabetes treatment
• Anti-Diabetic medications
– Oral hypoglycemic agents
• Sulfonylureas
• Thiazolidinediones
• Biguanides
• Alpha-glucosidase inhibitors
• Incretin mimetics and DPP-IV inhibitors
• Combinations

– Insulins
 Sulfonylureas
• Stimulate pancreas to secrete insulin
– Glibenclamide
• Glipizide, Glimepride, Glyclazide
• Adverse reactions
– Hypoglycemia
– Water retention/edema
– Photosensitivity
• May need to add insulin in times of stress
 Biguanides
• Decreases liver production of glucose
• Decreases intestinal absorption of glucose
• Improves cell sensitivity to insulin

• Example: Metformin
– GI upset, flatulence
– Cardiac (CHF, MI)
 Thiazolidinediones
• Increase cellular sensitivity to insulin
– Pioglitazone (Actos)
– Rosiglitazone (Avandia)

Client should have liver enzymes

checked periodically
 Incetin based therapies

• Incretin mimetics, Byetta

• DPPV-IV inhibition
 Combinations
• Glucovance
– Glyburide and Metformin
• Avandamet
– Avandia and Metformin
• Galvus-Met
– Vildagliptin and Metformin
 Insulin

• Made in beta cells of the pancreas

• Moves glucose into cells (thus acts like growth
hormone in a way)
• Moves potassium into cells (can buy time in
emergencies)
 Insulin preparations
given ONLY with syringes marked in “units”

• Rapid acting (lispro,

asparte)
• Short acting (regular)
• Intermediate acting
(NPH)
• Long acting
– Detamir(Levimir)
– Glargine(Lantus)
 Your learning

• Onset of action

• Peak (blood glucose will be lowest then)

• Duration
 Rapid acting insulin
• Lispro (Humolog, Novolog Aspart)
– Onset of action
• “15-30” minutes [may come on in 5 minutes…]

– Peak of action
• 1 - 2 hours

– Duration
• 3 – 4 hours
 Short acting insulins
• Regular (clear so can be given IV)
– Onset of action
• 0.5 to 1 hour

– Peak of action
• 2 – 4 hours

– Duration of action
• 6 – 8 hours
 Intermediate acting insulins
• NPH, Lente (chemicals added. Cloudy)
– Onset of action
• 1 – 4 hours

– Peak of action
• 4 – 12 hours

– Duration of action
• 18 – 24 hours
 Long acting insulins
• Ultralente
– Onset of action
• 4 – 8 hours

– Peak of action
• 18 hours

– Duration of action
• 24 – 36 hours
 Once a day insulin
• Glargine/Lantus
– Cannot be diluted or mixed in syringe with any
other insulin
– Slow, steady release
– Daily dosing [usually at bedtime]
– Lesser risk of rapid hypoglycemia
 Combination insulins
• 70/30 (70% NPH and 30% regular)
• Humolog 75/25 (NPH and Lente)

• Fewer injections
• Rotate sites to decrease lipodystrophy
 Pharmacokinetics of Insulin
• Injection site
• Absorption rate
• Injection depth
• Time of injection
• Mixing insulins
 Miscellaneous
• Byetta for type II Diabetics taking
sulfonylureas or combination
– Mimics physiologic glucose control
• Enhances insulin secretion only in presence of
hyperglycemia
• Insulin secretion decreases as blood glucose approaches
normal
 Some things to know

• Insulin moves potassium into cells

– Good for emergency situations
– Dangerous if potassium level already low
 Some things to know…
• HHNK (Hyperglycemic Hyperosmolar Non-
Ketotic Coma). Also called
– HHNK
– HNKS [syndrome]
• Like dibetic ketoacidosis, without the ketones
• Type II diabetic, makes enough insulin to avoid
ketones, but sugar builds up to dangerous levels ->
cellular dehydration
 Some things to know…

• Dawn Phenomenon vs Somogi’s effect

– Dawn phenomenon
• Blood sugar rises in early morning

– Somogi’s (rebound) effect

• Blood sugar rise in morning as reaction to
hypoglycemic time during the night