Diabetes Mellitus

Diabetes Mellitus :
a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both

Consists of 3 types:

1) Type 1 diabetes 2) Type 2 diabetes 3) Gestational diabetes

Complications :

- Stroke - Heart attack - Kidney disease - Eye Disease - Nerve Damage

Diabetes Mellitus
Type 1 Diabetes
- cells that produce insulin are destroyed - results in insulin dependence - commonly detected before 30

Type 2 Diabetes
- blood glucose levels rise due to
1) Lack of insulin production 2) Insufficient insulin action (resistant cells) - commonly detected after 40 - effects > 90% - eventually leads to -cell failure
(resulting in insulin dependence)

Gestational Diabetes
3-5% of pregnant women in the US develop gestational diabetes

Testing :
Fasting Plasma Glucose Test (FPG) - (cheap, fast) *fasting B.G.L. 100-125 mg/dl signals pre-diabetes *>126 mg/dl signals diabetes Oral Glucose Tolerance Test (OGTT) *tested for 2 hrs after glucoserich drink *140-199 mg/dl signals prediabetes *>200 mg/dl signals diabetes

Pancreas Endocrine Islets of Langerhans Alpha cells produce glucagon Delta cells produce somatostatin Beta cells produce insulin

Diabetes Insulin
(synthesis, storage, secretion)
Produced within the pancreas by cells islets of

Langerhans insulin mRNA is translated as a single chain precursor called preproinsulin removal of signal peptide during insertion into the endoplasmic reticulum generates proinsulin Within the endoplasmic reticulum, proinsulin is exposed to several specific endopeptidases which excise the C peptide, thereby generating the mature form of insulin
Stored as granules

In the case of type 1 diabetes, insulin levels are grossly deficient. Thus type 1 diabetes is invariably treated with insulin Type 2 diabetes is frequently associated with obesity. Serum insulin levels are normal or elevated, so this is a disease of insulin resistance. A number of treatment options may be employed.

The bulk of the pancreas is an exocrine gland secreting pancreatic fluid into the duodenum after a meal. Inside the pancreas are millions of clusters of cells called islets of Langerhans. The islets are endocrine tissue containing four types of cells. In order of abundance, they are: beta cells, which secrete insulin and amylin; alpha cells, which secrete glucagon; delta cells, which secrete somatostatin gamma cells, which secrete a polypeptide.

Pancreatic Hormones
Insulin Amylin Glucagon Somatostatin Pancreatic Polypeptide

Insulin affects many organs:

It stimulates skeletal muscle fibers. It stimulates liver cells. It acts on fat cells It inhibits production of certain glucose uptake glycogen synthesis amino acids uptake protein synthesis

enzyme.

fat synthesis

In each case, insulin triggers these effects by binding to the insulin receptor.

enzyme production

glycogen breaking

The insulin receptor (IR) is a transmembrane glycoprotein, composed of 2 and 2 domains.

.
Its intracellular tyrosine kinase domain is activated by binding of insulin, leading to a cascade of signaling events.

Hyperglycemia
When blood glucose becomes high

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

Diabetes Mellitus
Major risk factors Family history Obesity Origin (Afro-American, Hispanic, Native American, Asian-American) Age (older than 45) History of gestational diabetes High cholesterol Hypertension

Diabetes Mellitus
EFFECTS OF PREVENTION: combination

approach
Increased exercise
Decreases need for insulin

Reduce calorie intake

Improves insulin sensitivity

Weight reduction
Improves insulin action

Diabetes treatment
Diet Lower calorie Fewer foods of high glycemic index Spread meals evenly

Who need insulin medicine

Type I (insulin dependent) diabetes patients whose body

produces no insulin. Type 2 diabetes patients that do not always produce enough insulin.

Treatment
subcutaneous injection

Types of insulin

Regular insulins Insulin analogs Pre-mixed insulin

Short peptide mimics

Regular insulins:
Human insulin: Humulin (from E.coli),

Novalin (from yeast) NPH - neutral protamine Hagedorn (NPH), protamine mixed. Lente insulin / Ultralente insullinzinc added

Types of insulin

Regular insulins Insulin analogs Pre-mixed insulin

Short peptide mimics

Insulin Analogs:
Fatty Acid Acylated insulins Insulin Lispro (Humalog) (1996)

Insulin Aspart (NovoLog) (2000) Insulin Glargine (Lantus) (2002) Insulin Detemir (Levemir) (Jun.,2005) Insulin Glulisine (Apidra) (Jan., 2006)

Diabetes Oral Medications

6 Classes :
Sulfonylureas Biguanides
stimulate cells improves insulins ability to move glucose

Sulfonylureas and biguanide combination

drugs BOTH Thiazolidinediones cells more sensitive to insulin Alpha-glycosidase inhibitors Block enzymes that help
digest starches

Meglitinides

stimulate cells (dependant upon glucose conc.)

Glycemic Index
compares equal quantities of carbohydrate in foods
is a measure of their effect on blood

glucose levels in healthy people over a 2 hr period

provides a measure of carbohydrate

quality.

Traditional starchy foods have a lower GI1

Barley Legumes/beans Pastas Specialty breads Muesli Porridge oats

THE END