CHAPTER 33

DIABETES MELLITUS AND THE METABOLIC SYNDROME

Essentials of Pathophysiology

PRE LECTURE QUIZ

Type 2 diabetes is more common than type 1. All cells can use fatty acids interchangeably

with glucose for energy. Insulin is produced by the pancreatic beta

cells in the islets of Langerhans. Hyperglycemia is characterized by headache,

difficulty in problem solving, disturbed or altered behavior, coma, and seizures.

Chronic complications of diabetes mellitus refer only to type 1 diabetes mellitus.

T

F

T

F

F

PRE LECTURE QUIZ ______________ lowers the blood glucose

concentration by facilitating the movement of glucose into body tissues.

Glucagon, a polypeptide molecule produced by the _____________ cells of the islets of Langerhans, maintains blood glucose between meals and during periods of fasting.

Type __________ diabetes mellitus is characterized by destruction of the pancreatic beta cells and is characterized by an absolute lack of insulin, an elevation in blood glucose, and a breakdown of body fats and protein.

The ________________ syndrome is a condition of abnormalities that are identified through specific criteria such as abdominal obesity, elevated triglycerides, elevated blood pressure, elevated fasting plasma glucose, and decreased high-density lipoprotein cholesterol (HDL).

Diabetic ____________________ occurs when ketone production by the liver exceeds cellular use and renal excretion.

Alpha

Insulin

ketoacidosis

Metabolic

one

ANABOLISM AND CATABOLISM

Anabolisminsulin, anabolic steroids

Catabolismglucagon,

epinephrine, cortisol

available foodstuffs (in blood)

glucose

amino acids

free fatty acids

stored foodstuffs (in cells)

glycogen

proteins

triglycerides

liver can convert amino acids and free fatty acids into

ketones

INSULIN AND GLUCAGON ARE THE MAIN CONTROLS

Anabolisminsulin , anabolic steroids

Catabolismglucagon , epinephrine,

cortisol

available foodstuffs (in blood)

glucose

amino acids

free fatty acids

stored foodstuffs (in cells)

glycogen

proteins

triglycerides

liver can convert amino acids and free fatty acids into

ketones

QUESTION

Tell whether the following statement is true or false.

Anabolic reactions release energy.

ANSWER

FalseRationale: Anabolic reactions use

energy to build/produce/synthesize (like building proteins from amino acids). Catabolic reactions break down substances, releasing energy in the process (like digestion).

SCENARIO

Two women have benign pancreatic tumors. In one, the tumor is an insulinoma that secretes

insulin In the other, the tumor is a glucagonoma that

secretes glucagon

Questions: What differences do you expect to see between

these two women? Why? Both of the women have arthritis, but only one is

being treated with corticosteroids. Which one? Why is the other not receiving corticosteroids?

THE PANCREAS

pancreas

exocrine pancreas

releases digestive juices through a

duct

to the duodenum

endocrine pancreas

releases hormones into the blood

endocrine pancreas: islets of

Langerhans

alpha cells beta cells delta cells PP cells

pancreatic polypeptide

glucagon insulinand amylin somatostatin

FUNCTIONS OF PANCREATIC HORMONES

Glucagon: causes cells to release stored food into the blood

Insulin: allows cells to take up glucose from the blood

Amylin: slows glucose absorption in small intestine; suppresses glucagon secretion

Somatostatin: decreases GI activity; suppresses glucagon and insulin secretion

QUESTION

Which pancreatic hormone decreases blood glucose levels?

a. Glucagonb. Insulinc. Amylind. Somatostatin

ANSWER

b. InsulinRationale: Insulin allows cells to take

glucose from the blood and use it for energy/to make ATP. Because it stimulates movement of glucose out of the blood and into the cells, blood glucose levels decrease when insulin is released.

DISCUSSION

Think back on your day so far.

When do you think you had your highest insulin levels?

When do you think you had your lowest insulin levels?

When did you have your highest glucagon levels?

DISCUSSION

Review the figure on insulin’s actions. If someone lacks insulin, what

happens to his: Blood glucose levels? Blood amino acid levels? Blood pH? Intracellular fat levels? Intracellular protein levels? Cell growth?

DISCUSSION

Review the following diagrams on anabolism/catabolism and insulin’s mechanism of action.

Questions: Identify five things that could go wrong to cause

increased blood glucose Which of the cases you identified would be least

likely to respond to insulin?

ANABOLISM AND CATABOLISM

Anabolisminsulin, anabolic steroids

Catabolismglucagon,

epinephrine, cortisol

available foodstuffs (in blood)

glucose

amino acids

free fatty acids

stored foodstuffs (in cells)

glycogen

proteins

triglycerides

liver can convert amino acids and free fatty acids into

ketones

TYPES OF DIABETES MELLITUS

Type 1: pancreatic beta cell destruction predominantly by an autoimmune process

Type 2: a combination of beta cell dysfunction and insulin resistance

Other Genetic defects in insulin production Genetic defects in insulin action Diabetes secondary to other diseases Drug interactions

Gestational diabetes mellitus

PATHOGENESIS OF TYPE 2 DIABETES

QUESTION

Tell whether the following statement is true or false.

Type 2 DM is more common than type 1 DM.

ANSWER

TrueRationale: Type 1 DM is autoimmune

(juvenile diabetes is type 1), and affects only 5–10% of the diabetic population. Type 2 DM is associated with risk factors like obesity, poor diet, and sedentary lifestyle; 90–95% of diabetics suffer from this type.

METABOLIC SYNDROME

Abdominal obesity

Increased blood triglyceride levels

Decreased HDL levels

Increased blood pressure

Increased fasting plasma glucose

TREATMENTS FOR TYPE 2 DIABETES

ACUTE COMPLICATIONS OF DIABETES

Diabetic ketoacidosis

Hyperglycemic hyperosmolar nonketotic coma

Hypoglycemia

Somogyi effect

Dawn phenomenon

ACUTE COMPLICATIONS OF DIABETES (CONT.)

Discussion How would hyperglycemia with ketoacidosis

cause: Heavy breathing? Polyuria? Dehydration?

Which of these would you not see in hyperglycemia without ketoacidosis?

SCENARIO

You find a man collapsed on the sidewalk.

He is wearing a diabetic alert bracelet and has an insulin syringe in his briefcase

Questions:

Does he need insulin?

Why or why not?

What signs might help you tell whether he has a hyperglycemic or hypoglycemic problem?

CHRONIC COMPLICATIONS OF DIABETES MELLITUS Increased glucose levels allow

glucose to bind to proteins in: Hemoglobin Hb A1C has higher O2

affinity Basement membranes of blood vessels

º Nephropathy

º Retinopathy

º May cause increased risk of atherosclerosis

Lens cataracts(Porth, C. M. [2005]. Pathophysiology [7th ed.]. Lippincott Williams & Wilkins andGreenspan, F. & Gardner, D. G. [2004]. Basic and clinical endocrinology [7th ed.]. McGraw-Hill.)

OSMOLARITY IN DIABETES MELLITUS

When blood glucose is high, increased blood osmolarity can cause cells to shrink

Nerve cells produce intracellular osmoles to keep their osmolarity balanced with the blood

A

B

Hypotonic cell A shrinks

Cell B is in osmotic balance

(Porth, C. M. [2005]. Pathophysiology [7th ed.]. Lippincott Williams & Wilkins.)

OSMOLARITY IN DIABETES MELLITUS (CONT.)

When the client brings blood glucose back to normal, the nerve cells are hyperosmolar to the blood and gain water, swelling

Nerve damage may be caused by swelling, demyelination, and lack of O2 secondary to vascular disease

A

B

Cell A is in osmotic balance

Hypertoniccell B swells

(Porth, C. M. [2005]. Pathophysiology [7th ed.]. Lippincott Williams & Wilkins.)

DIABETIC NEUROPATHY

Somatic neuropathy Diminished perception of vibration, pain,

and temperature Hypersensitivity to light touch;

occasionally, severe “burning” pain Autonomic neuropathy

Defects in vasomotor and cardiac responses

Impaired motility of the gastrointestinal tract

Inability to empty the bladder Sexual dysfunction

QUESTION

Which of the following is not a complication of diabetes mellitus?

a. Nephropathyb. Retinopathyc. Neuropathyd. All of the above are complications of

DM.

ANSWER

d. All of the above are complications of DM.

Rationale: Nephropathy and retinopathy are caused by increased blood glucose levels that cause binding of excess glucose to the basement membranes of the blood vessels of the kidneys and eyes. Neuropathy is due to swelling and demyelination of nervous tissue.

DIABETIC FOOT ULCERTypical Diabetic Foot Ulcer Advanced Diabetic Foot Ulcer