Diabetes Mellitus Types I & II

James Bresnahan, MS1Robert Gyory, MS1

Introduction• How does your body make use of glucose from

the food you eat?• What is the difference in etiology between type 1

and type 2 diabetes? How does this affect treatment?

• What is the homeostatic balance between insulin, glucose, glucagon, and stress hormones? How does this differ between nonaffected individuals vs. type 1 diabetics vs. type 2 diabetcs?

• Why does high blood glucose cause other complications?

• What are some psychosocial considerations regarding diabetes?

Glycogen is a good form of storage. It’s condensed, easily broken down, and its byproducts are used efficiently to make energy.

α-1,6-linkageα-1,6-linkage

α-1,4-linkageα-1,4-linkage

I thought T1DM is about insulin?

Without insulin…

How do you get Type 1 “Diabeetus?”

-No!!

-T1DM is AUTOIMMUNE.-Destruction of Pancreatic B-islet cells.

-What about T2DM? Ask Rob..

What are B-Islet cells? How are they destroyed?

• Genetic predisposition• Environmental stimuli

– Lead to antibodies that attack pancreatic Beta cells

-Diagnosis is bimodal with peaks at 4-6 years and 10-14 years-3M:2F??-23.6 per 100,000 per year.

What are the general effect

Clinical Presentation

How do you treat T1DM?

Future?

How do Endocrinologists monitor their diabetic patients over long periods of time?

So, high glucose is bad, what about low glucose?

-Low blood glucose is FAR more detrimental in terms of short term problems.

-Diabetic coma due to Neuroglycopenia

- Glucagon is released by a-cells in RESPONSE to b-cells not making insulin (a sign of high BG.) If B-cells are destroyed, a-cells can’t release glucagon.

Future ways to monitor T1DM?

http://www.youtube.com/watch?v=w0aalblWfjU

Take into consideration different ethical issues ranging from cost of supplies/equipment to the mental demands of current T1DM patients.

Diabetes Mellitus Type II

But first, a biochemical interlude: Downregulation vs. Upregulation

Adapted from the common domain of Cornell University

The mechanism of DM II is a complex sequence of biochemical processes

1) Diet high in fat and carbohydrates + sedentary lifestyle highly elevated plasma [glucose]

2) Chronically ↑ plasma [glucose] chronic overstimulation of β cells and chronic hypersecretion of insulin

3) Chronic hypersecretion of insulin down regulation of insulin receptors on adipocytes and skeletal muscles

Down regulation of insulin receptors exhibits a number of negative consequences

• ↓ glucose uptake by cells– ↓ glucose for cells to use

for energy

– ↑↑ plasma [glucose]

• Can cause relatively minor symptoms or serious DM I type symptoms

Adapted from the University of Arizona Dept. of Biological Sciences

What are the consequences of decreased glucose for cellular energy?• Cells begin to burn fats

for energy. – Can cause pH problems

(DKA)– Inefficient fuel source

leads to fatigue, low energy, etc.

*Important: Glucose uptake is severely decreased, but not nonexistent as in DM I

What are the consequences of elevated plasma [glucose]?

• DM Type I Symptoms– e.g. polyuria, polydypsia,

glycosuria, etc.

• Hypertrophy of β cells– Extremely chronic

hyperstimulation can lead to β cell destruction

– Leads to insulin dependence

Beta cells stained in green

What are the symptoms of Type II diabetes mellitus?

• Some patients may be asymptomatic for many years

• Others experience lighter versions of many of the symptoms of diabetes mellitus I

• Rarely, DKA and other complications can occur such as hyperosmotic coma

• Why do these symptoms differ from DM I when their mechanisms of pathogenesis are so similar?

How is DM II diagnosed?

• Chronically high fasting plasma [glucose]

• Elevated glycated hemoglobin pattern (HbA1C)

• In difficult cases, insulin immunoassay

Treatments for DM II are widely variable

• For most people, diets lower in fats and carbohydrates coupled with exercise will correct the down-regulation of insulin receptors

• Others need medications such as biguanides and sulfonylureas (e.g. metformin) to decrease endogenous glucose production

• Severe cases in which beta cells have been destroyed will need to supplement with insulin– ‘insulin dependent’ diabetes

Biguanides versus sulfonylureas

• Biguanides– Metformin– Phenoformin– Buformin– Proguanil

• Sulfonylureas– Carbutamide– Tolbutamide– Chlorpropamide– Acetohexamide– And others….

The prognosis and sequelae of DM II are very similar to DM I

Sequelae

• In well controlled diabetics, there are very few resulting problems

• With poor control, however:– Poor circulation vascular

disease and cardiovascular problems

– Neuropathy

– Other metabolic dysfunctions

Prognosis

• If a person controls their condition well, they can either live an asymptomatic life or go into remission altogether

• With poor control, however:– Myocardial infarction, stroke,

blindness, amputation, degenerative brain disorders, renal failure, death

Diabetes mellitus II is one of the most preventable disease in our society

• Obesity is the number one predictor of DM II– Healthy diet and plenty of

exercise are needed

– Patient education!!!

• Prior patient knowledge about the various genetic and medical factors that can increase DMII predisposition

Systemic Insulin Regulation

How do hormones and other factors regulate insulin?

The following hormone pathways work to help regulate the action of insulin

• Epinephrine and cortisol inhibit insulin and increase secretion of glucagon in the pancreas– HPA axis

• Growth hormone directly acts on the pancreas to cause glucagon secretion

• Glucagon inhibits insulin secretion and causes biochemical effects that are opposite those of insulin

Other friends that you’ve met throughout the year that effect insulin secretion

• ↓ insulin secretion– Thyroxine and T3

– Norepinephrine

– Low ATP

– And others

• ↑ insulin secretion– High ATP

– Somatostatin

– Leptin

– And others

Learning objectives for this lecture

1. Review the biochemistry, pathology, and medical treatments of diabetes mellitus 1 and 2

2. Provide a general overview of biochemical dysfunction, resulting metabolic derangement, compare and contrast the risks and sequelae, and discuss the treatments for both diseases and why treatments are specific to only one disease and not the other

3. Discuss the utility of HbA1c measurement as a method of monitoring treatment efficacy

4. Discuss patient, doctor, and psychosocial issues surrounding diabetes mellitus

5. Discuss the prevalence of diabetes mellitus, long term risks to patients, and cost of care issues

6. Discuss quality of life issues7. Discuss the importance of primary prevention in diabetes mellitus 2