Glucose Metabolism & Diabetes

How does diabetes disrupt the homeostatic levels of

glucose in the blood?

Objectives

•Describe the major structures and functions of the liver and pancreas.

•Explain the intricacies of glucose, protein, and fat metabolism.

•Explain the roles of insulin and glucagon in maintaining homeostasis.

•Explain the processes of lipolysis, deamination glycogenolysis, and gluconeogenesis.

•Define the terms glycosuria, polyuria, polydipsia, and polyphagia and explain why diabetes causes these conditions.

•State the medical complications associated with diabetes and explain why these occur.

PART I

LIVER & PANCREAS: STRUCTURE FUNCTION

THE LIVER: Structure•Largest visceral organ in the body 1.5 kg (3.3 lb.), 4 lobes

•Sinusoids (blood vessels-similar to capillaries) between liver cells (hepatocytes) empty into the central vein

THE LIVER: Structure•Functional unit of

the liver: Liver lobule (50,000-100,000): cylindrical structure, several mm long 1-2 mm in diameter

•Central vein in center of lobule

THE LIVER: Structure

•Hepatocytes in a liver lobule form a series of irregular plates arranged like the spokes of a wheel

•Portal area between lobules: hepatic artery, interlobular portal vein, interlobular bile duct

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LIVER •Blood flowing from the intestinal capillaries picks up many bacteria from the intestines.

•When bacterium comes into contact with a Kupffer cell (phagocytic cell: engulf pathogens, cell debris, and damaged blood cells) in less than 0.01 sec it passes inward through the cell membrane and gets lodged until it isdigested.

•Less than 1% of incoming bacteria escapes to circulation.

Sinusoid with red blood cell and Kupffer cell

HEPATIC PORTAL CIRCULATION

•Blood from the spleen, pancreas, stomach & intestines enters the liver via the hepatic portal vein.•Blood from the intestines is

very high in glucose.•Liver cells remove excess glucose, amino acids, toxins, bacteria.•Blood leaves the liver by means of the hepatic vein, now with normal levels of glucose.

LIVER: Function• Filtration and storage

of blood.• Metabolism of

carbohydrates, proteins, fats, and hormones.

• Storage of vitamins and minerals.

• Synthesis of plasma proteins.

• Synthesis and secretion of bile.PHAGOCYTE

Filtration of the blood

THE PANCREAS: Structure•The pancreas is approximately 20 cm (8 in) and weighs about 80g (3 oz)

•The pancreas has two major types of tissues: the acini (secrete digestive juices to duodenum) and the islets ofLangerhans (secrete insulin and glucagon directly into blood)

•Human pancreas has 1 – 2 million islets of 0.3 mm in diameter, although the islets account for only about 1% of the pancreatic cell population

THE PANCREAS: Structure

Ref: http://camel.campbell.edu/~nemecz

•Islets of Langerhans contain 3 types of hormone-secreting cells Alpha cells (25%) Beta cells (60%)

Delta cells (10%) F cells (PP cells) (5%)•The islets are organized around small capillaries into which the

cells secrete their hormones

THE PANCREAS: Structure/Function–Alpha cells secrete glucagon- elevates blood glucose concentrations

–Beta cells secrete insulin- reduces blood glucose concentrations

–Delta cells secrete somatostatin- slows the rate of food absorption and digestive enzyme secretion

–F cells/PP cells secrete pancreatic polypeptide

• Close interrelation among various cell types allow regulation of secretion of some hormones by other hormones: insulin inhibits glucagon secretion, somatostatin inhibits insulin and glucagon secretion

www.umassmed.edu/diabeteshandbook/chap01.htm

PART II

HOW DO THE LIVER & PANCREAS ALLOW US

TO UTILIZE THE NUTRIENTS WE

CONSUME?

Glucose: the preferred nutrient

• Carbohydrates are the preferred source of energy for the body.

• Final products of carbohydrate digestion in the digestive tract are monosaccharides (glucose [80%], fructose and galactose)

• Much of fructose and all galactose are converted to glucose in the liver and released back into the blood.

• Glucose is a large molecule that must be broken down into a form of energy usable by the cell (ATP).

health.howstuffworks.com/diabetes1.htm

Structure of ATP: Adenosine Triphosphate

A P P P

adenosine Phosphate groups

High-energy bonds

CATABOLISM: Molecule Breakdown

A P P P

Glucose is broken down into many molecules of ATP (higher # if O2 present)

A P P P+

C6H12O6

When bond is broken, energy is released to do cellular work

AdenosineDiphosphate

Glucose Metabolism

•The process of glucose metabolism involves 1) glycolysis, 2) the citric acid cycle (Krebs cycle) 3) electron transport.

1-cytoplasm; 2, 3-mitochondria

•Complete reaction:C6H12O6 + 6O2 >>

6CO2 + 6H2O

•Net gain = 36 ATP

•Only 40% of the energy released through catabolism of glucose is captured in ATP.

•The remaining 60% escapes as heat that warms the interior of the cells and the surrounding tissues.

•If cells have inadequate amounts of glucose to catabolize, the immediately shift to the catabolism of fats for energy.

•In starvation, proteins are used for energy after carbohydrate and fats are depleted.

Fat & Protein Metabolism

•Triglycerides >> Fatty acids & Glycerol (lipids)•Proteins >> amino acids

•Lipids and amino acids are broken down into molecules that can enter the citric acid cycle

•LIPOLYSIS: catabolism of lipids•DEAMINATION: catabolism of amino acids

•Fatty acids or glycerol or amino acids >>intermediate compounds >>Citric Acid Cycle >> ETS >> ATP

Triglycerides Glycogen Proteins

Fatty Acids Glycerol Glucose Amino Acids

Pyruvicacid

Acetyl-CoA

CitricAcid

Cycle

Alternative Catabolic Pathways

Electron Transport

ATP Production

mitochondrion

cytoplasm

REGULATION OF NUTRIENTS

Insulin regulates the uptake of nutrients into the cells, the

storage of nutrients not being used, and the conversion of one nutrient type to another.

Metabolic Efficiency: Glucose

•Cells rely on insulin for efficient absorption of glucose from the blood (except brain cells)

•Insulin also enhances ATP production

•Without insulin not enough glucose is supplied to tissues for energy metabolism

SIMPLY PUT, insulin can be thought of as the funnel that

allows glucose to pass through the receptors into

cells. S= SUGAR (glucose)

A SIMPLIFIED VIEW OF THE MECHANISM OF INSULIN

Insulin & its chemistry•Insulin is a small protein (MW of human insulin 5808) composed of two amino acid chains connected by two disulfide linkages.

•Secreted by beta cells, insulin circulates in blood in unbound form.

•It has a plasma half-life of about 6 min and is cleared from circulation in 10 – 15 min

•Insulin not combined with receptors in target cells are degraded by insulinase -mostly in liver andalso in kidneys and muscles

Connecting peptide (white) joins the two chains

21

30

A Chain

B Chain

INSULIN MOLECULE

Protein of 21 amino acid A chain and 30 amino acid B chain, Disulfide linkages

•The insulin receptor is a combination of 4 subunits held together by disulfide linkages: two α-subunits lying outside the cell membrane and two β-subunits protruding into the cell cytoplasm.

Mechanism of Action of Insulin*

Mechanism of Insulin

•When insulin binds to the α-subunit in target tissues, the β-subunits in turn become activated.

• Activation of the β-subunits triggers a series of reactions that draw the glucose transporter to the cell membrane.

• Cells (liver, muscle, adipose, but not brain) are now able to increase their uptake of glucose. (w/in seconds after insulin binds with its membrane)

• The cell membrane also becomes more permeable to many amino acids.

Mechanism of Action of Insulin*

Mechanism of Action of Insulin*

Ref: http://www.diabetes.org/

Mechanism of Action of Insulin

Insulin: Glucose Storage•Only enough ATP for immediate cellular requirements is made at any one time

•Glucose that is NOT needed for ATP is ANABOLIZED into glycogen and stored for later use in the liver and in muscles.

•GLYCOGENESIS: synthesis of glycogen from glucose molecules

•Insulin – stimulates glycogenesis (glycogen anabolism) – inhibits glycogenolysis (glycogen catabolism)

Why is glucose stored as glycogen?

•Glucose is in liquid form. As the number of glucose molecules increases, the pressure inside the cell increases.

•Converting glucose to glycogen (in solid form) relieves pressure inside the cell.

Glucose Conversion to Fat

• Excess glucose is preferentially stored as glycogen BUT

• When cells are saturated with glycogen (liver cells store 5 to 8% of their weight as glycogen, muscle cells 1 to 3%) additional glucose is converted to fat in the liver and stored as fat in adipose cells.

Insulin: Glucose>>Fat Storage

•Insulin promotes the conversion of all excess glucose in liver that cannot be stored as glycogen into fatty acids

•Fatty acids are packaged as triglycerides in low density lipoproteins transported by blood to adipose tissue

•Insulin activates lipoprotein lipase in the capillary walls of adipose tissue, which splits triglycerides into fatty acids. This enables them to be absorbed into adipose cells where they are converted again to triglycerides and stored.

Insulin: Protein Metabolism

• Insulin (like growth hormone) stimulates transport of amino acids into cells.

• Insulin increases the translation of messenger RNA, thus forming new proteins.

Insulin: Protein & Fat Metabolism

• Insulin and growth hormone interact synergistically to promote growth

• Insulin stimulates the absorption of fatty acids and glycerol by adipocytes, where they are stored as triglycerides.

Summary: Metabolic Effects of Insulin

•Increases rate of glucose transport into target cell•Increases rate of glucose utilization and ATP

formation•Increases conversion of glucose to glycogen (liver,

skeletal muscle)•Increases amino acid absorption and protein

synthesis•Increases triglyceride synthesis (adipose tissue)

*DECREASES HIGH BLOOD GLUCOSE LEVELS*

THE REGULATION OF BLOOD GLUCOSE

↑Blood Glucose

Beta Cells in Islets of

Langerhans

Stimulus

Receptors

Increased Insulin secretion and

synthesis

Intracellular communication

↑Blood Glucose

Beta Cells in Islets of

LangerhansReceptors

Stimulus

THE REGULATION OF BLOOD GLUCOSE

Liver cells

Muscle and fat cells throughout body

Insulin carried in blood

Increased Insulin secretion and

synthesis

Intracellular communication

↑Blood Glucose

Beta Cells in Islets of

LangerhansReceptors

Stimulus

↑Glucose uptake

↓Blood Glucose

↓Blood Glucose

↓Glucose synthesis•GlycogensynthesisResponse

THE REGULATION OF BLOOD GLUCOSE

Negative Feedback

Liver cells

Muscle and fat cells throughout body

Insulin carried in blood

Efferent Pathway

Effectors

Increased Insulin secretion and

synthesis

Intracellular communication

↑Blood Glucose

Beta Cells in Islets of

LangerhansReceptors

↑Glucose uptake

↓Blood Glucose

↓Blood Glucose

↓Glucose synthesis•GlycogensynthesisResponse

Stimulus

THE REGULATION OF BLOOD GLUCOSE

…and LOW blood glucose…

After the meal is over and blood glucose level begins to fall to a low level:

–The pancreas decreases insulin secretion–Glycogen synthesis in liver is stopped–Glucose uptake by liver from blood is prevented

If blood glucose levels continue to fall,- GLUCAGON will increase the RELEASE of glucose from the cells

…and for more glucose…GLUCAGON also causes:

–GLYCOGENOLYSIS: Breakdown of glycogen into glucose

–GLUCONEOGENESIS: Increase of synthesis of glucose from amino acids and the glycerol portion of fat

FOR ADDITIONAL NUTRIENTS…

•GLUCAGON causes:– LIPOLYSIS: Activation of adipose cell lipase

making fatty acids available for use as energy source

•GLUCAGON is a large polypeptide composed of a chain of 29 amino acids and has a molecular weight of 3485. Secreted by alpha cells.

Somatostatin

• A polypeptide with 14 amino acids with a 3 min half-life in blood. Same chemical substance as growth hormone inhibitory hormone. Secreted by delta cells.

• All factors related to ingestion of food stimulate somatostatin secretion

• Somatostatin has many inhibitory effects: Depresses secretion of insulin and glucagon– Decreases motility of stomach, duodenum and

gallbladder– Decreases secretion and absorption in GI tract

• It extends the period of time for assimilation of food

Pancreatic Polypeptide

• Secreted by F cells• Inhibits gallbladder contractions• Regulates the production of some

pancreatic enzymes• May help control the rate of nutrient

absorption by the digestive tract

Part III

Diabetes:What’s the problem?

glycogenesis glycogenolysis triglyceride synthesis ketogenesis gluconeogenesis

glucose uptake protein synthesis protein degradation glycogenesis

glycogenolysis

glucose uptake triglyceride storage lipolysis

Review: Endocrine Effects of Insulin

StimulatesStimulates Inhibits Inhibits• Liver

• Skeletal Muscle

• Adipose tissue

Promotes anabolic Promotes anabolic processesprocesses

Inhibits catabolic Inhibits catabolic processesprocesses

Importance of Insulin•Without insulin, glucose transport into the cells will be insufficient.

Lacking glucose, cells will have to rely on protein and fat catabolism for fuel.

•Also, when there is not enough insulin, excess glucose cannot be stored in the liver and muscle tissue.

Instead, glucose accumulates in the blood-- above normal levels.

The high concentration of glucose in the

blood (resulting from the lack of insulin) is called

hyperglycemia, or high blood sugar.

Blood Glucose

• Fasting blood glucose concentration (person who has not eaten in the past 3-4 hours) – Normal person: 80 - 90 mg / 100 ml– Diabetic patient: 110 - 140 mg / 100 ml

• After a meal: – Normal person: 120 - 140 mg / 100 ml– Diabetic patient: < 200 mg / 100 ml

EXCESS OF BLOOD GLUCOSE…

• Exerts high osmotic pressure in extracellular fluid, causing cellular dehydration

• Excess of glucose begins to be lost from the body in the urine: GLYCOSURIA

GLYCOSURIA >>> •Excessive glucose in the kidney filtrate acts as an osmotic diuretic, inhibiting water reabsorption resulting in POLYURIA: huge urine output >>> decreased blood volume and dehydration.

•Dehydration stimulates hypothalamic thirst centers, causing POLYDIPSIA: excessive thirst.

OTHER SIDE EFFECTS of POLYURIA

•The dehydration resulting from polyuria also leads to dry skin.

•During a period of dehydration, blurred vision can be caused by fluctuations in the amount of glucose and water in the lenses of the eyes.

POLYPHAGIA

•POLYURIA, POLYDYPSIA, & POLYPHAGIA= THE 3 CARDINAL SIGNS OF DIABETES

•POLYPHAGIA: excessive hunger and food consumption, a sign that the person is “starving in the land of plenty.” That is, although plenty of glucose is available, it cannot be used, and the cells begin to starve.

•Without fuel, cells cannot produce energy >> fatigue and weight loss.

Insulin deficiency >> metabolic use of FAT

• A deficiency of insulin will accelerate the breakdown of the body’s fat reserves for fuel.

• Free fatty acids become the main energy substrate for all tissues except the brain.

• Increased lipolysis results in the production of organic acids called ketones (KETOGENESIS) in the liver.

KETOGENESIS>>KETOSIS

•The increased ketones in the blood lower the pH of blood, resulting in a form of acidosis called KETOSIS, or ketoacidosis.•Ketones are excreted in the urine: KETONURIA.

Complications of KETOSIS:

•Serious electrolyte losses also occur as the body rids itself of excess ketones.

•Ketones are negatively charged and carry positive ions out with them.

•Sodium and potassium are also lost from the body; because of the electrolyte imbalance, the person get abdominal pains and may vomit, and the stress reaction spirals even higher.

•Can result in coma, death

Effects of insulin deficiency on metabolic use of fat

•Excess fat metabolism leads to an increase in plasma cholesterol >>> increased plaque formation on the walls of blood vessels.

•Leads to atherosclerosis & other cardiovascular problems: cerebrovascular insufficiency, ischemic heart disease, peripheral vascular disease, and gangrene.

Effects of insulin deficiency on metabolic use of fat

• Degenerative changes in cardiac circulation can lead to early heart attacks. Heart attacks are 3-5 times more likely in diabetic individuals than in nondiabetic individuals. The most common cause of death with diabetes mellitus is myocardial infarction.

Other complications of diabetes:

•A reduction in blood flow to the feet can lead to tissue death, ulceration, infection, and loss of toes or a major portion of one or both feet. •Damage to renal blood vessels can cause severe kidney problems. (Nephropathy)•Damage to blood vessels of the retina can also causeblindness. (Retinopathy)

Non-Proliferative Retinopathy

•Blood vessels in the retina leak and hemorrhage. Patient may notice a decrease in vision if the swelling and hemorrhage affect the macula.

•Macula edema is the most common cause of visual loss in diabetic retinopathy.

Non-Proliferative Diabetic Retinopathy

Fundus photo of normal macula Hemorrhages in non-proliferative diabetic retinopathy

Proliferative Retinopathy

New blood vessels grow in the eye.

These new blood vessels tend to bleed and leak causing vision loss.

These new blood vessels may also pull on the retina causing retinal detachment.

Proliferative Diabetic Retinopathy

New blood vessel growth around optic nerve in

proliferative diabetic retinopathy

Hemorrhage from new blood vessel growth in

proliferative diabetic retinopathy

Side Effects of Excess Sugar•Loss of vision due to cataracts: Excessive blood

sugar chemically attaches to lens proteins, causing cloudiness.

•Skin infections sometimes occur because excess sugar in the blood suppresses the natural defense mechanism like the action of white blood cells. And sugar is an excellent food for bacteria for food to grow in.

BACTERIA CELLS

Periodontitis•High blood glucose also helps bacteria in the mouth to grow, making tooth and gum problems worse.

•Gingivitis: bacteria grow in the shallow pocket where the tooth and gum meets; gum begins to pull away from the tooth. Progresses to:

•Periodontitis: infection causes actual bone loss, teeth begin to pull away from the jaw itself

Latter Stages of Periodontitis

Damage to the Nerves•Numbness and tingling in feet

and night leg cramps may result from nerve damage due to prolonged high glucose levels that cause changes in the nerves and “neuron starvation” from lack of cellular glucose.

•Nerve damage can also lead to a loss of the ability to feel pain in the feet, leading to undue pressure>>calluses>> ulceration. (Neuropathy)

Diabetic Neuropathy•Neuropathy can result in two sets of what appear to be contradictory problems. Most patients who have neuropathy have one these problems but some can be affected by both:

1) symptoms of pain, burning, pins and needles or numbness which lead to discomfort

2) loss of ability to feel pain and other sensation which leads to neuropathic ulceration

Diabetic NeuropathyPatients with neuropathy lose their sensation of pain. As a result, they exert a lot of pressure at one spot under the foot when they walk, building up a callus at that site without causing discomfort. The pressure becomes so high that eventually it causes breakdown of tissues and ulceration.

A TYPICAL NEUROPATHIC ULCER IS…

1) PAINLESS

2) SURROUNDED BY CALLUS

3) ASSOCIATED WITH GOOD FOOT PULSES

(BECAUSE THE CIRCULATION IS

NORMAL)

4) AT THE BOTTOMOF THE FOOT

& TIPS OF TOES

Malfunction of hormone signal in target cells

Undiscovered mechanisms

Hyposecretion of Insulin

Increased blood glucose level

(hyperglycemia)

Decreased glucose available

for cellular respiration

Decreased insulin effects

Increased glucose ininterstitial fluid

Kidney’s ability to conserve

glucose is exceeded

Increased urine glucoselevel (glycosuria)

Increased volume of urine (polyuria)

Provides nutrients formicroorganisms

Increased susceptibilityto infection

Water follows glucose into

urine by osmosis

Net water loss frombody

Thirst(polydipsia)

EFFECTS OF DECREASED INSULIN

= signs & symptoms

Malfunction of hormone signal in target cells

Undiscovered mechanisms

Hyposecretion of Insulin

Increased blood glucose level

(hyperglycemia)

Decreased glucose available

for cellular respiration

Decreased insulin effects

Coma

Neurons“starve”

CardiovascularDisorders

Eye (retina)damage

Nerve diseases

Acidosis

Shift from usingcarbohydrates to

using fats

Gallstones

BlindnessKidneydamage

Ulcers &Gangrene

HeartDisease

WeightLoss

Increased blood lipid levels

(hyperlipidemia)

Production ofketone bodies

= signs & symptoms

EFFECTS OF DECREASED

INSULIN

Increasedlipolysis

INSULINDEFICIENCY

Polyphagia

Increasedfree fatty acids

(FFA)

Glycosuria

Hyperglycemia

Volume depletion

DIABETICCOMA

Polyuria

PolydipsiaIncreased FFA oxidation (liver)

Ketoacidosis

EFFECTS OF DECREASED

INSULIN

Glucose and insulin secretion

BLOOD GLUCOSE

TIME (MIN)5 10 15 20

PLASMAINSULIN

CONCENTRATION

GLUCOSE TOLERANCE•Glucose tolerance is the body’s ability to manage its

blood sugar level within normal range. The Cori cycle is a strategy used by the body to accomplish

this. •The blood sugar of

normal individuals

can sometimes drop

to the hypoglycemic

level.–This can even be

caused by ingesting

too much sugar, trig-

gering the release

of extra insulin.

TOO MUCH OF A GOOD THING…

• Diabetics use insulin injections to treat high blood glucose levels. It is essential that blood glucose levels always be maintained above a critical level.

• Brain cells use only glucose for energy. When blood glucose levels fall too low (20 to 50 mg/ml), symptoms of hypoglycemic shock develop – nervous irritability leading to fainting, seizures and coma

Part Iv

Diabetes:

Type I Vs. Type II

History of Diabetes MellitusTIME

EVENT

1500 BC

Ebers Papyrus first describes diabetes

400 BC

Susruta records diabetes symptoms and classifies types of diabetes. Charaka refines this work in 6AD.

10 AD Celsus develops a clinical description of diabetes 20 AD Aretaeus coins the term diabetes.

1869 Langerhans describes clusters of cells (islets) in the

pancreas. 1889 von Mering and Minkowski observe that diabetes

develops when an animal's pancreas is removed. 1921 Banting and Best obtain and purify islets of Langerhans

from an animal pancreas, inject the material (insulin) into a diabetic animal, and find a fall in blood sugar level.

The disease’s name was derived from two terms:

Diabetes– Greek for siphon or fountain for the characteristic

frequent urination

Mellitus– Latin for sweet as honey. In 1679, a physician tasted the

urine of a person with diabetes and described

as sweet like honey.

Type I or Insulin-Dependent Diabetes Mellitus

(IDDM) The pancreas makes no

insulin. It is a result of progressive and irreversible destruction of the

islets by the patient's immune system.

Treatment:

Blood Glucose

Measurements

Daily Insulin Injections

Exercise & Diet

Type II or Non-Insulin Dependent Diabetes Mellitus

(NIDDM) The pancreas produces some

insulin, but often, not sufficient to lower the blood glucose level to

normal.

Treatment:

Blood Glucose Measurements

Oral Medication

Exercise & Diet

Insulin Injections

TYPES OF DIABETES

Type 1 (previously called Type I; Insulin-dependent diabetes mellitus, IDDM, juvenile diabetes)

• Pathophysiology– Immune-mediated destruction of ß cells– Idiopathic

• Absolute insulin deficiency- insulin therapy required

• Accounts for 5 to 10 percent of cases• Diabetes Control and Complications Trial

(DCCT) showed that control of glycemia slows the onset and progression of eye, kidney, and nerve complications

Classification of Diabetes Mellitus

Pathophysiology of IDDM

Age (years)

Stages in the Development of Diabetes Mellitus

Genetic predispositionOvert Immunologicabnormalities

Normal insulinrelease

Progressiveloss of insulin release

Glucosenormal

Overtdiabetes

C-peptidepresent

NoC-peptide

β-cell mass

Juvenile (14 years of age)

Classification of Diabetes Mellitus

Type 2 (Type II; Non-insulin-dependent diabetes mellitus, NIDDM)

• Ranges from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance

• Insulin therapy required in 20-30% patients; oral hypoglycemic drugs used in most cases; diet and exercise sufficient in mild cases

• Accounts for 90 to 95 percent of the 18 million cases in the United States.

Type I vs. Type II Diabetes

Type I (IDDM) Type II (NIDDM)

Age at onset Usually under 40

Usually over 40

Body weight Thin Usually overweight

Symptoms Appear suddenly

Appear slowly

Insulin produced None Too little, or it is ineffective

Insulin required Must take insulin

May require insulin

Other names Juvenile onset diabetes

Adult onset diabetes

CAUSES OF DIABETES•Two factors especially important in the development of diabetes:

1) Heredity: About a 5% risk of developing Type II diabetes if mother, father, or sibling has diabetes. Higher risk (up to 50%) if overweight.

2) Obesity: 80% of people w/ Type II diabetes are overweight when diagnosed and symptoms disappear in many of the obese patients when they lose weight.

Other causes/triggers of diabetes:

•Age: As people age, their bodies may have fewer insulin-producing beta cells.

•Faulty immune system: Scientists now believe that there is not one cause of diabetes, but multiple factors that may trigger the immune system to destroy beta cells.

Viruses: Certain viruses may destroy beta cells in susceptible people.

Other causes/triggers of diabetes:•Physical trauma: An accident or injury may destroy the pancreas, where insulin is normally produced.

•Stress: Hormones released during periods of stress may block the effect of insulin.

•Pregnancy: Hormones produced during pregnancy may block the effect of insulin.

•Drugs: Drugs prescribed for another condition may

unmask diabetes.

Maintaining Control

•Protect heart, nerves, blood vessels, eyes, and kidneys by controlling blood glucose level.

•Maintain schedule for checking blood glucose level and taking insulin.

•Maintain well-balanced meal plan, exercise program, and healthy weight.

How does exercise help?

Most of the time muscle tissue depends on fatty acids for energy •Under two conditions muscles use large amounts of glucose:

– During moderate or heavy exercise (muscle fibers become permeable to glucose even in the absence of insulin– important in Type I)

– During the few hours after a meal (while pancreas is secreting more insulin– important in Type II). Most of the glucose is stored as muscle glycogen.

The Diabetic Meal Plan

•Under this plan, 60 to 70 percent of your total daily calories should come from grains, beans, and starchy vegetables, with the rest being meat, cheese, fish and other proteins.

•Fats, oils, and sweets should be used sparingly. The Diabetes Food Pyramid suggests the following daily servings of food for people with diabetes:

DIABETES FOODPYRAMID

The Diabetes Food Pyramid differs from the standard Food Guide Pyramid in the way that it groups different foods together.

•Because blood glucose is of primary concern to people with diabetes, the Diabetes Food Pyramid focuses on the way in which certain foods affect blood glucose levels.

•For example, in the standard pyramid, beans and legumes are grouped with meats, due to their protein content. In the diabetes pyramid, however, beans are grouped with starches, because they affect blood glucose in the same way that starchy foods do.

And ONE LASE TIME, why are…

•Maintaining a well-balanced meal plan, exercise program, and healthy weight

AND

•Maintaining a schedule for checking blood glucose levels taking insulin

SO IMPORTANT??????

Heart Disease and Stroke

•Heart disease is the leading cause of diabetes-related deaths. Adults with diabetes have heart disease death rates about two to four times higher than adults without diabetes.

•The risk for stroke is two to four times higher among people with diabetes.

•About 65 percent of deaths among people with diabetes are due to heart disease and stroke.

Blindness

•Diabetes is the leading cause of new cases of blindness among adults aged 20-74 years.

•Diabetic retinopathy causes 12,000 to 24,000 new cases of blindness each year.

Kidney Disease•Diabetes is the leading cause of end-stage renal disease, accounting for 44 percent of new cases.

•In 2001, 42,813 people with diabetes began treatment for end-stage renal disease.

•In 2001, a total of 142,963 people with end-stage renal disease due to diabetes were living on chronic dialysis or with a kidney transplant.

Nervous System Disease

•About 60 percent to 70 percent of people with diabetes have mild to severe forms of nervous system damage. The results of such damage include impaired sensation or pain in the feet or hands, slowed digestion of food in the stomach, carpal tunnel syndrome, and other nerve problems.

•Severe forms of diabetic nerve disease are a major contributing cause of lower-extremity amputations.

Amputations

•More than 60 percent of non- traumatic lower-limb amputations occur among people with diabetes.

•In 2000-2001, about 82,000 non-traumatic lower-limb amputations were performed annually among people with diabetes.

One final look at the homeostatic mechanism

in question:

In diabetes, where is the missing link?

Can you rememberall of the

biochemical consequences???

The physicalconsequences??