diabetes mellitus

pancreas

Large diffuse abdominal organ

functions of pancreas

◼ Endocrine gland

◼ Exocrine gland

pancreas composed of 2 major tissue types:

◼ Acini
◼ Islets of Langerhans

exocrine pancreas function

Involves synthesis & release of

◼ Digestive enzymes ◼ Sodium bicarbonate

Secreted by acinar cells & contents released into pancreatic duct

◼ Plays essential role in digestion & absorption of food in small intestine

endocrine pancreas function

Involves synthesis & release of hormones

◼ Produced by specialized cells in Islets of Langerhans

Play essential role in blood glucose levels

insulin is produced by which cells in pancreas?

beta cells

glucagon is produced by which cells in pancreas?

alpha cells

somatostatin is produced by which cells in pancreas?

delta cells

insulin action

decrease Blood glucose by allowing it to enter cells

glucagon action

increase Release of glucose from the liver into the blood

somatostatin action

decrease Gastrointestinal activity after ingestion of food → extends time over which food is absorbed

Inhibits insulin & glucagon → extends use of absorbed nutrients by tissues

maintenance of blood glucose after a meal

AFTER A MEAL: Glucose levels rise → insulin secreted in response

◼ Glycogenesis

◼ Lipogenesis

maintenance of blood glucose between meals

Liver releases glucose to maintain blood glucose within normal limits

◼ Glycogenolysis

◼ Gluconeogenesis

Glycogenesis

2/3 of glucose from meal is stored in liver as glycogen

Lipogenesis

when tissues saturated with glycogen → glucose converted to fatty acids → stored as triglycerides in fat cells

Glycogenolysis

glycogen broken down to release glucose

Gluconeogenesis

synthesis of glucose from amino acids, glycerol, and lactic acid

glycemic control chart

glucose action

increase Glucose transport into skeletal & adipose tissue

increase Glycogen synthesis
decrease Gluconeogenesis

fats action

increase Glucose transport into fat cells

increase Fatty acid transport into adipose cells

increase Triglyceride synthesis within fat cells
Inhibits adipose cell lipase
Activates lipoprotein lipase in capillary walls

proteins action

increase Active transport of amino acids into cells

increase Protein synthesis by increase transcription mRNA & accelerating protein synthesis by rRNA

decrease Protein breakdown by enhancing use of glucose & fatty acids as fuel

major insulin action on tissues

decrease Blood glucose by allowing it to enter target cells

anabolic activity of insulin action on tissues

Promotes synthesis of proteins, CHOs, lipids, nucleic acids in liver, muscle, adipose

insulin action on liver

Stimulates: synthesis of glycogen & increase uptake; and fatty acid synthesis
Inhibits: glycogenolysis, gluconeogenesis, ketogenesis

insulin action on muscle

increase uptake glucose & amino acids

increase glycogen & protein synthesis

Inhibits protein catabolism

insulin action on adipose

increase glucose uptake & fat synthesis (lipogenesis)

decrease fat breakdown

insulin actions on K+

increases K+ uptake by cells

insulin action on lipids

Metabolism of plasma lipids & lipoproteins WNL ranges

K+ =

3.5-5.5 (narrow window)

normal funciona of insulin

increase Uptake of blood glucose into cells

decrease Blood glucose levels

excess insulin leads to

hypoglycemia

hypoglycemia

low Blood glucose

◼ Hunger
◼ Tremor
◼ Sweating

◼ Weakness
◼ Malaise
◼ Irritability
◼ Mental changes

◼ Coma → DEATH

deficit of insulin

hyperglycemia

hyperglycemia

high Blood glucose

◼ Polydipsia - thirst

◼ Polyphagia - hunger

◼ Polyuria – UO

◼ Dehydration

◼ Fatigue

◼ Mental changes

◼ Coma → DEATH

glucagon action

opposite of insulin

glucagon function

• travels via portal vein to liver where it exerts its main effects

  ◼ Stimulates glycogenolysis & gluconeogenesis
  ◼ Increases lipolysis & output of ketones by liver

  ◼ Enhances uptake of amino acids by the liver

glucagon secretion inhibited by?

glucose

action of glucagon on glucose

Promotes breakdown of glycogen into glucose phosphate

Increases gluconeogenesis

action of glucagon on fats

Enhances lipolysis in adipose tissue → liberates glycerol for use in gluconeogenesis
Activates adipose cell lipase
Enhances lipolysis in adipose tissue → liberates fatty acids

action of glucagon on proteins

Increases breakdown of proteins into amino acids for use in gluconeogenesis

catecholamines are produced by?

adrenal medulla

◼ Epinephrine & norepinephrine

which is more severe/faster killing: hypoglycemia or hyperglycemia?

hypoglycemia

catecholamines function

Maintain blood glucose levels during stress

◼ Mobilizes glycogen stores
◼ Decreases movement of glucose into body cells

◼ Inhibits insulin release from beta cells
◼ Mobilizes fatty acids from adipose tissue

catecholamine is an important?

homeostatic mechanism during periods of hypoglycemia

◼ Purpose → conserve glucose!

growth hormone functions

◼  Increase protein synthesis in ALL cells of body

◼  Mobilizes fatty acids from adipose tissue

◼  Antagonizes the effects of insulin

◼  Decreases cellular uptake and use of glucose →increases blood glucose by as much as 50-100% →stimulates further insulin secretion

growth hormone inhibited by

insulin & increased levels of blood glucose

growth hormone increases in

◼ Fasting

◼ Exercise: running, cycling
◼ Stress: anesthesia, fever, trauma

growth hormone responses chart

where is glucocorticoid hormone synthesized?

• in adrenal cortex
  ◼ Cortisol (hydrocortisone) responsible for 95% of activity

what do glucocorticoid hormone regulate?

• metabolism of glucose
  ◼ Critical to survival during periods of fasting & starvation

what does glucocorticoid hormone stimulate?

• gluconeogenesis by the liver (increased production 6-10x)

what does glucocorticoid hormone moderately decrease?

use of tissue glucose

glucocorticoid hormone levels increase in:

◼ Stress: infection, pain, trauma, surgery, prolonged strenuous exercise, acute anxiety

◼ Hypoglycemia: a potent stimulus for secretion

GLP 1

(glucagon-like peptide-1)

GIP

(glucose-dependent insulinotropic polypeptide)

GIPS function

• Are incretin hormones released from your gut

• Signal the beta cells to increase insulin secretion &

  decrease the alpha cells’ release of glucagon

GLP 1 function

• slows down the rate at which food empties from the stomach & acts on the brain to increase satiety

examples of GLP 1

• Ozempic, Trulicity and Victoza

example of Dual GIP/GLP-1

Mounjaro

amylin

Released along with insulin from beta cells

Has much the same effect as GLP-1

◼ Decreases glucagon levels, which will then decrease the liver’s glucose production,

◼ Slows the rate at which food empties from the stomach

◼ Acts on the brain to increase satiety

diabetes

Disorder of carbohydrate, protein & fat metabolism- “the running through of sugar”

◼ Multiple etiologic factors

diabetes involves:

Involves absolute or relative insulin deficiency and/or insulin resistance

◼ Absolute insulin deficiency
◼ Impaired release of insulin by pancreatic beta cells

◼ Inadequate or defective insulin receptors
◼ Production of inactive insulin
◼ Insulin is destroyed before it carries out its action

diabetes makes it so that you cannot…

carry glucose into fat & muscle cells → cellular starvation → breakdown of fat and protein

Diabetes is likely to be _______ as a cause of death.

underreported

8th leading cause of death

the risk for death among people with diabetes is about twice that of people without diabetes of similar age.

diabetic comortbidites

• Diabetes is the leading cause of kidney failure, lower-limb amputations, and adult- onset blindness in the US.

• The risk for heart disease and stroke is 2-4 times higher for those with diabetes than those without.

• More than 20% of health care spending is

  for people diagnosed with diabetes

comorbidities with pediatric pts with type 1 DM

◼ Nephropathy
◼ Hypertension
◼ Dyslipidemia

◼ Celiac Disease

◼ Hypothyroidism

type 1 diabetes characteristics

Absolute insulin deficiency

type 1 diabetes etiology

A. Autoimmune

B. Idiopathic

type 1 diabetes treatment

insulin

type 2 diabetes characteristics

Insulin insensitivity

Insulin secreting deficiency

Inappropriate gluconeogenesis

type 2 diabetes etiology

Obesity

Genetics

type 2 diabetes treatment

Diet

Exercise

Hypoglycemics

Transporter- Stimulators

other specific diabetes etiology and treatment

Malnutrition

Corticosteroids

treatment based on cause

GDM characteristic

Gestational diabetes

GDM etiology

increase Metabolic demands

GDM treatment

Diet

Hypoglycemics

LADA

Latent Autoimmune Diabetes of Adults

◼ Form of Type 1, slower progression to need for insulin, sometimes called “Diabetes Type 1.5"

MODY

Maturity-onset Diabetes of the Young

◼ Inherited, autosomal dominant;

◼ Younger than 30 years of age

type 1 formerly named

Juvenile onset

Insulin dependent

IDDM
Type I

type 2 formerly named

Adult onset

Non-insulin Dependent

NIDDM
Type II

type 1 onset

Any age
< 30 usually

type 2 onset

Usually after 40

8/10 obese

pathophysiology type 1

NO insulin production

pathophysiology type 2

Produce insulin BUT not enough or tissues are resistant

type 1 major complications

DKA
(cell starvation)

type 2 major complications

HHNK
(less ketosis)

manifestations of type 1

Hyperglycemia & glucosuria

◼ Symptoms develop more acutely

Recurrent blurred vision, fatigue, paresthesias, recurrent skin infections & yeast infections

3 p’s/polys of manifestations of type 1:

• Polyuria – excessive urination d/t osmotic diuresis when

reabsorption capacity of renal tubules exceeded

• Polydipsia – excessive thirst d/t intracellular dehydration including cells of the thirst center & mouth

•  Polyphagia – excessive hunger d/t cellular starvation & depletion of cellular stores of CHOs, fats & proteins

Weight loss despite normal or increased appetite with type 1

◼ Osmotic diuresis; vomiting d/t ketoacidosis
◼ Cells must use stored CHOs, fats & proteins for energy

pathogenesis of type 2 chart

manifestations of type 2

Hyperglycemia & glucosuria

◼ Symptoms often develop more insidiously

Recurrent blurred vision d/t exposure of lens & retina to hyperosmolarity

 Weakness + fatigue d/t lowered plasma volume

Paresthesias d/t dysfunction of peripheral sensory nerves

Chronic skin infections d/t hyperglycemia + glucosuria favor growth of yeast → pruritus & vulvovaginitis

Often symptoms that prompt individual to seek Tx

obesity

2 ps with type 2

◼ Polyuria – same mechanism

◼ Polydipsia – may be overlooked b/c glucose increase is more gradual & no ketoacidosis

Genetic defects of beta-cell function

Chromosome 7, 12, 20, Mitochondrial DNA

Genetic defects in insulin action

Leprechaunism , Rabson-Mendenhall, Lipoatrophic

Diseases of the exocrine pancreas

Pancreatitis, trauma/pancreatectomy, neoplasia, cystic fibrosis, hemochromatosis

Endocrinopathies

Acromegaly, Cushing's syndrome, glucagonoma,

pheochromocytoma, hyperthyroidism

Drug- or chemical-induced

Vacor, Pentamidine, Nicotinic acid, Glucocorticoids, Thyroid

hormone, Diazoxide, Beta-adrenergic agonists, Thiazides, Dilantin

Infections

Congenital rubella, Cytomegalovirus

Casual or Random Plasma Glucose (PG)

ANY time of day without regard to time since last meal

◼ > 200 mg/dL

Fasting Plasma Glucose (FPG) (no caloric intake x 8hrs)

Once preferred d/t ease of administration, convenience,

acceptability to patients, & lower cost

◼ FPG<126mgperdL