9 blood glucose

Blood Glucose• Normal Fasting Blood Glucose = 80 – 100 mg/dl

• Post-Prandial Blood Glucose = 100 – 120 mg/dl

mmol/lmg/dl

1.730

4.480

8.3150

14.0250

22.2400

1.Carbohydrate of diet

2.Liver glycogen by glycogenolysis

3.10% of Fat of diet by gluconeogenesis

4.58% of Protein of diet by gluconeogenesis

5.Lactate from blood & RBCs by gluconeogenesis

Sources of Blood Glucose

Factors Regulating Blood Glucose

1.Gastrointestinal tract factors

2.Hepatic factors (Glucostat organ)

3.Renal factors

4.Hormonal factors

1.Gastrointestinal factors:

• Oral carbohydrate diet stimulates more insulin

than intra-venous glucose

• This may be due to secretion of glucagon-like

substance by intestine which stimulates -cells

of pancreas to secrete more insulin



2.Hepatic factors (Glucostat organ):

A- If blood glucose level increased, liver decreases it by:

1. Oxidation of glucose (Glycolysis & Kreb’s)

2. Glycogenesis

3. Lipogenesis

B- If blood glucose level decreased, liver increases it by:

1. Glycogenolysis

2. Gluconeogenesis

3. Conversion to fructose and galactose into glucose


3. Renal factors:

• Normal Renal Threshold for Glucose =

180 mg/dl

• Some patients may have Renal Diabetes,

in which Renal Threshold is less than

140 mg/dl

1. Glucagon:

29 amino acid polypeptide

Major target organ: liver

Have no receptors on muscle cell

Principal hormone for producing a rapid

increase in plasma glucose concentration

Dominates in Fasting State Metabolism

Stimulates production of glucose by

glycogenolysis and gluconeogenesis

Secretion is suppressed in hyperglycemia

4.Hormonal factors:

Endocrine response to hypoglycemia Glucagon Action on Cells

2. Epinephrine “fight or flight”

A catecholamine secreted by the adrenal medulla

Stimulates glucagon secretion and inhibits insulin

secretion

Stimulates glycogen breakdown (glycogenolysis)

and decreases glucose oxidation

Physical/emotional stress epinephrine

production, releasing glucose for energy

Gluconeogenesis

Lipolysis

Glycogenolysis

Only hormone (besides insulin) needed to keep you alive

Maintains general functioning of body

metabolism and regulates blood pressure

Secreted by adrenal cortex in response to ACTH of

pituitary gland

Cortisol causes breakdown of muscle protein,

leading to amino acid release in blood

Liver uses amino acids to make glucose

(Gluconeogenesis!)

Cortisol increases blood sugar!

3. Cortisol “Stress Hormone”

4. Growth Hormone (GH) Primary function: stimulates growth of soft

tissue, bone, and cartilage

Secondary function: Effect on plasma glucose:

1. Inhibition of glucose uptake by peripheral

cells

2. Stimulation of liver glycogenolysis

3. Acceleration of fatty acid catabolism

(Stimulation of gluconeogenesis)

Prolonged excess of GH (Acromegaly):

Mild hyperglycemia, abnormal Oral Glucose

Tolerance Test (OGTT)

5. ACTH

ACTH stimulates the production

of glucocorticoids

Glucocorticoids stimulate

gluconeogenesis

6. Thyroxin

• It increases the blood glucose level by:

1. Increases the rate of absorption of glucose

from intestine

2. Stimulates gluconeogenesis

3. Stimulates glycogenolysis

4. Thyroxine also stimulates glucose

oxidation in tissues

5. However the net effect of this hormone is

the increase in blood glucose level

7. Glucocorticoids • These hormones are secreted from zona fasiculata

• They are hyperglycemic (Insulin antagonistic action)

• They produce their effect by:

1. Inhibiting glucokinase

2. Stimulating glucose-6-phosphatase

3. Inhibiting tissue uptake of glucose

4. Stimulating gluconeogenesis

On the other hand, Glucocorticoids

5. Stimulating glycogenesis by increasing the

activity of glycogen synthase enzyme

8. Insulin First hormone identified (1920’s) by

Banting and Best

Tied string around pancreatic ducts of

dogs or removed ducts. Only thing left

were thousands of pancreatic islets,

Isolated protein…and discovered

insulin!

Insulin is a hormone that is needed to

convert sugars, starches, and other

food into energy needed for daily life

7. Insulin

Fed-state metabolism

• Circulating insulin

rapidly binds to

receptors on cell

surfaces, increases

glucose entry into

cells and alters

metabolic pathways

Action of

glucagon and

insulin on the

liver, muscle, and

adipose tissue.

Phases of Glucose Homeostasis

Nutritional

StatusWell-Fed Post-absorptive

Gluconeogenic

(early)Prolonged

Origin of

Blood

Glucose

ExogenousHepatic glycogen,

Gluconeogenesis

Hepatic

glycogen,

Gluconeogenesis

Gluconeo-

genesis

Tissues

Using

Glucose

All

All except liver.

Muscle, adipose

diminished rates

Brain & RBC's;

Small amount by

Muscle

Brain

Slow rate;

RBCs normal

Major Fuel

of the

Brain

Glucose Glucose Glucose Ketone bodies

glucose from

gluconeogenesis

(mostly lactate)

4 8 12 16 2 7 42

Exogenous

(glucose

from diet)

40

30

20

10

0

Glu

cose

Use

d g

/hr

Fed Post absorptive Gluconeogenic Prolonged

HOURS DAYS

Sources of blood glucose in the various nutritional states

glucose from

liver glycogen

glucose from

gluconeogenesis

(lactate + amino acids)

Maintenance of blood glucose concentration

depends on insulin and glucagon

Brain depends on glucose

Prolonged starvation has <25% decline in

glucose

Hyperglycemia – too little insulin

Hypoglycemia – too little intake or too much insulin

Summary of Blood Glucose Homeostasis

Under conditions where insulin levels are high, the

number of receptors declines and the target tissues

become less sensitive, resulting in “down regulation”

22%

45%

Glucose Homeostasis

Blood Glucose, What’s “normal”?

Pancreas Pancreas, controls blood glucose levels by

secreting hormones into the blood

Islet of Langerhans (, , )

1. -cells (20-30% of islet cells) Glucagon

2. -cells (60-70% of islet cells) Insulin

3. -cells (2-8% of islet cells) Somatostatin

After high

carbohydrate dietBetween

meals

Role of

Pancreas in

Normalizing

Blood

Glucose

Level

Distribution of Glucose After Meal

Insulin released when glucose is elevated in plasma

Insulin increases peripheral tissue uptake, so

muscle and fat cells remove glucose from blood

Cells breakdown glucose, releasing its energy in the

form of ATP (via glycolysis and Kreb’s cycle)

Liver and muscle store glucose as glycogen (short-

term energy reserve)

Adipose tissue stores glucose as fat (long-term

energy reserve)

Cells use glucose in protein synthesis

Insulin is the ONLY hormone that lowers circulating

glucose level!

Distribution of Glucose After Meal

Insulin Synthesis

Transcription and Translation of the

Insulin Protein First, the DNA coded information (blue helix) in the cell

nucleus is copied, or transcribed, to an RNA mirror

image (red strand).

Second, the ribosome (tan) translates the linear pattern

described in the RNA to construct a protein strand. This

translation is based on the Genetic Code (background

text).

Transfer-RNA's (Cross-like shapes) ferry (moving)

amino acids to the growing protein chain based on the

3-codon RNA sequence.

Finally, the Insulin protein strand folds itself into its

active form.

Transcription &

Translation of the

Insulin Protein

DNA coded information

inside the Nucleus

mRNA

tRNA

Ribosome

Insulin

molecule

Transcribed RNA

Tertiary

Structure

of Insulin

1

(24)

4

(21)

2

(30)

3

(35)

Preproinsulin

31 Arg

32 Arg

64 Lys

65 Arg

[Connecting peptide]

Aids in transporting insulin

through the membrane

Preproinsulin

Synthesized in Ribosomes

Aids in transporting insulin

through the membrane

Proinsulin

In Endoplasmic Reticulum

Insulin

In Golgi Apparatus

Synthesized in Ribosomes

In Endoplasmic Reticulum

In Golgi Apparatus

Leader

(Signal) chain

A chain 21 amino acids

B chain 30 amino acids

Post-translational

Processing of

Insulin

Mechanism of Action of Insulin

Muscle

Mechanism of Action of Insulin1. Increases peripheral tissue uptake (Fat, RBC’s

& Muscle cells)

NORMALLY IN THE BODY


1. Increases peripheral tissue uptake (Fat,

RBC’s & Muscle cells)

2. Induces synthesis of enzymes of:

a- Glycolysis (3 enzymes)

b- Kreb’s cycle (Pyruvate DH)

c- Pentose shunt (2 enzymes)

3. Stimulates glycogenesis (1 enzyme)

4. Inhibits glycogenolysis (1 enzyme)


5. Inhibits gluconeogenesis (4 enzymes)

6. Stimulates Lipogenesis (Supplies Acetyl

Co A, -Glycerol phosphate, NADPH &

ATP)

7. Inhibits lipolysis (1 enzyme)

8. Stimulate transamination (Pyruvate to

Alanine), (1 enzyme)

Glycolysis

Protein

synthesis

Lipogenesis

Glycogenesis1

2

3 4

Oral Glucose Tolerance Test (OGTT)

Collect fasting blood samples for determination

of blood glucose and urine samples for detection

of glucose in urine

Give the patient (1g/Kg body weight, max. 50 g)

glucose in half cup of water

Every 30 min. collect a blood samples and urine

samples, for 2.5 – 4 hr

Draw a relation between blood glucose level

(mg/dl) against time (hr)


Renal

Diabetes

Severe

Diabetes

Moderate

Diabetes

Mild

DiabetesNormal ParameterNo

70 – 110

mg/dl

> 180 mg/dl140 – 180

mg/dl

70 – 140

mg/dl

70 – 110

mg/dl

Fasting

Blood

Glucose1

After 1 hrAfter 1 hrAfter 1 hrAfter 1 hrAfter 1 hrPeak

Time2

< 140 mg/dl> 270 mg/dl 230 – 270

mg/dl

< 180

mg/dl

< 140

mg/dl

Peak

Value3

2:00 hr4:00 – 5:00

hr

2:30 – 4:00

hr2:30 hr2:00 hr

Time of

return to

Fasting

Level

4

Present in the

Middle of the

Samples

Present in

all

Samples

Present in the

Middle of the

SamplesAbsentAbsent

Glucose

in

Urine

Samples

5

Diabetes Mellitus

Prof. Dr.

Mamdouh El-Shishtawy

A medical disorder

characterized by hyperglycemia

(elevated blood glucose level)

especially after eating

Diabetes Mellitus

“Diabetes“ is a Greek word meaning “passes

through, a siphon”, due to polyuria

“Mellitus” is a Greek word meaning “sweet”

This is due to the diabetic’s urine attracts flies &

bees because of its glucose content

The Ancient Chinese test for diabetes by observing

whether ants were attracted to a person’s urine

Diabetes

Disease in which the body:

Does not produce insulin, or

Does not properly use insulin

Diabetes Warning signs:

Extreme thirst (Polydipsia)

Frequent urination (Polyuria)

Unusual fatigue or drowsiness

Unexplained weight loss

Blurry vision from time to time

Diabetes is the leading cause of kidney

failure, blindness, and amputation in

adults, and can also lead to heart disease

Main Types of

Diabetes Mellitus (D.M.)

Type I (IDDM)

Insulin Dependent

Diabetes Mellitus

Type II (NIDDM)

Non-Insulin

Dependent Diabetes

Mellitus

Other Types of Diabetes Mellitus (D.M.)

(Non Type 1 – Non type 2)

•Type 3:

• Type 3A: Genetic defect in β-cell function

• Type 3B: Genetic defect in insulin action

• Type 3C: Diseases of the exocrine pancreas

• Type 3D: Caused by hormonal defects

(Endocrinopathies)

• Type 3E: Caused by chemicals or drugs

• Type 4: Gestational D.M.

It appears in 2 – 5% of all pregnancies

It is temporary & fully treatable under medical

supervision

About 20 – 50% go on to develop type II diabetes

Other Types of Diabetes Mellitus (D.M.)

Other Classes of D. M.

5. Diabetes insipidus:

due to deficiency of

Vasopressin (ADH)

polyuria

Other Classes of D. M.

6. Renal diabetes: due to congenital defect in

renal threshold for glucose (140 mg/dl or

less)

7. Stress diabetes (Emotional diabetes): due to

secretion of catecholamines

8. Bronze diabetes: due to excessive absorption &

deposition of iron in pancreas:

a) Hyperglycemia D.M.

b) Skin Bronze in color,

c) Liver Cirrhosis

9. Steroid diabetes: due to secretion or prolonged

administration of glucocorticoids

10. Pituitary diabetes: due to over-secretion of Growth

hormone (Acromegaly)

7. Experimental diabetes:

a) Alloxan diabetes Uncontrolled diabetes

b) Streptozotocin diabetes Controlled

diabetes

c) Surgical diabetes:

i. Total pancreatectomy

ii. Partial pancreatectomy

8. Drug-induced diabetes: large doses of

dehydroascorbic acid

Causes of Diabetes Mellitus

Insufficient production of Insulin

Increased production of anti-insulin hormones,

e.g.:

1. Cushing's syndrome ( Cortisone)

2. Hyperthyroidism ( Thyroid Hormone)

3. Acromegaly ( Growth Hormone)

21

Risk Factors for Diabetes Mellitus

3 1

4 2

5 6

7 8

9 10

Cellular phones and remote controls deprive us from walking!

20 times daily x 20 m = 400 m

Walking distance lost/year400x365 = 146,000 m

146 km = 25 h of walking

1 h of walking = 113-226 kcal

Energy saved =2800-6000 kcal

Rössner, 2002

High-Tech increases Body

Weight

0.4-0.8 kg adipose tissue

Increased Time at Computer/TV/Video

Decreases Time for Leisure-Time

Physical Activity

>

New Remote Control

Can Be Operated by

Remote

• Television watching became

even more convenient with

Sony’s introduction of a new

remote-controlled remote

control

• No more leaning

forward to get

remote from coffee

table means greater

convenience for TV

viewers

Eat to

Live!Live to Eat!

“EAT TO LIVE”

Intake = Expenditure

Weight Stable

“LIVE TO EAT”

Intake > Expenditure

Obese

reveals itself in childhood.

can be made worse from excessive lifestyle.

It is caused by the destruction of insulin-producing

cells (-cells of islets of Langerhans of pancreas)

IDDM may be due to:

1. -cell destruction may be due to:

a) -cell lesions (trauma or tumor)

b) Viral infection

c) Chemical toxins (rat poison)

2. Autoimmune mediated disorder

3. Idiopathic (Unknown cause)

Type I (IDDM)

Insulin Dependent Diabetes

It is an autoimmune disorder, so confused with

type II

Known by misleading names: Juvenile

(Childhood) onset diabetes (under 20–30 years)

Usually accompanied with loss of body weight

Characterized by Diabetic Ketoacidosis (DKA)

Diabetic Coma

Type I (IDDM)

Type I IDDM Lipid metabolism

Fatty acid production

Ketone formation

Decreased glucose

uptake & Protein

metabolism

Glycogenolysis

Gluconeogenesis

Decreased glucose

uptake

Symptoms of Type 1 Diabetes

Increased thirst

Increased hunger (especially after eating)

Dry mouth

Frequent urination (polyuria)

Unexplained weight loss (even though

you are eating and feel hungry)

Fatigue (weak, tired feeling)

Blurred vision

Labored respiration (heavy breathing, تنفس

(Kussmaul respirations) (جهذي

Loss of consciousness (rare)

In this case, the pancreas continues to

manufacture insulin. However, this production may

be inadequate or normal

For some unknown reason, the body develops

resistance to insulin, thus resulting in a relative

insulin deficiency

Type II (NIDDM)

Non-Insulin Dependent Diabetes

NIDDM may range from:

1. Insulin resistance with relative insulin deficiency, to:

2. Insulin secretary defect with insulin resistance

Insulin resistance may be due to:

a) Decreased number of insulin receptors, or

b) Insensitivity of insulin receptors to insulin

Type II (NIDDM)

DIABETES TYPE 2:

INSULIN RESISTANCE

This is a more complex problem than type I,

but is sometimes easier to treat

Known by misleading names: “Adult onset

diabetes” (over 40 years), “Obesity-related

diabetes” due to gain of body weight, or

“Insulin-resistant diabetes”

Chronic obesity leads to increased insulin

resistance that can develop diabetes

Type II (NIDDM)

Type II Diabetes Mellitus

Insulin resistance

Decreased glucose

uptake with any

amount of insulin

Insulin Receptors

Insulin Resistant Cell

Insulin Shock

People who accidentally take too much insulin

may be victims of insulin shock

The symptoms of insulin shock include:

Agitation

Trembling

Sweating

Pallor

Speech difficulty

Unconsciousness

الهياج

اإلرتعاد

التعرق

الشحوب

صعوبة الكالم

فقذ الوعي

Insulin Shock

Someone suffering from the preliminary

symptoms is given sugar in the form of sweets or

fruit

An unconscious patient is given an injection of

adrenaline into muscle, or glucose solution into a

vein

Symptoms of Type 2 Diabetes

Slow-healing sores or cuts

Itching of the skin (usually in the

vaginal or groin area)

Yeast infections

Recent weight gain

Numbness (نمل ؛ اخذرار) or tingling

of the hands and feet (نخز)

Impotence or erectile dysfunction

Bases of Treatment of

Diabetes Mellitus

It is treated with:

1. Insulin injections, human insulin is often

preferred in initiating insulin treatment because

it is less antigenic than animal-derived varieties

2. lifestyle adjustment

3. Monitoring of blood glucose levels

4. Experimental replacement of -cells (-cells

Transplant) may become clinically available in

future

5. Patient may requires immuno-suppressor drug,

e.g.: “Cyclosporine”

Type I (IDDM) Diabetes Mellitus

Type II may go unnoticed for years in patients

before diagnosis, due to milder symptoms (No

ketoacidosis) and can be sporadic

1. Patient must reduces body weight (Diet) or

Lifestyle Modification, which can restore insulin

sensitivity

2. Patient requires muscular exercise

3. Patient may require an oral antidiabetic drugs

4. When these failed, insulin therapy may be

necessary

Basis of Treatment of Type II (NIDDM)

Type I diabetes is usually prompted by

recent symptoms of:

Excessive urination (Polyuria)

Excessive thirst (Polydipsia)

Weight loss

Diabetic ketoacidosis (DKA)

The diagnosis of other types of

diabetes is made by:

Health screening

Detection of hyperglycemia

Signs & symptoms of D.M.

Diagnosis of Diabetes Mellitus

1. Two fasting plasma glucose level

above 125 mg/dl

2. Plasma glucose above 200 mg/dl two

hours after a 50 g glucose load

3. Symptoms of D.M. and a random

glucose above 200 mg/dl

4. Elevated glycosylated or glycated

hemoglobin (glucose bound to Hb,

HbA1C) of 6.0 or higher

Criteria for Diagnosis of Diabetes Mellitus

Hypoglycemia may occur because of:

An error in insulin dosage

A small or missed meal

Unplanned exercise

Hypoglycemia, usually respond rapidly

to the ingestion of sugar

All diabetics should carry candy,

lumps of sugar, or glucose tablets

Hypoglycemia

An identification card, indicating that the patient is

an insulin-treated diabetic, aids in recognizing

hypoglycemia in emergencies

Close family members should be instructed to

administer glucagon with an easy-to-use injection

device

Emergency medical personnel, after confirming

the hypoglycemia with a glucostick, should initiate

therapy with a rapid bolus injection of 25 ml of

50% glucose solution followed by a continuous IV

infusion of glucose

Manifestation & Complication of Diabetes

Hyperglycemia

Glucosuria

Hyperphagia (eating too much)

1- Carbohydrate Disturbances

Hyperlipemia

Fatty liver

Ketonemia

Ketoacidosis

Ketonuria

Coma


2- Lipid Disturbances

Hypercholesterolemia

Atherosclerosis

Gangrene

Amputation


2- Lipid Disturbances (Cont.)

Negative N2 balance

Weakness & wasting of muscles

3- Protein Disturbances


Osmotic diuresis

Polyuria

Dehydration

Polydepsia (Thirsty)


4- Water Disturbances

Cataract

Neuropathy

Nephropathy

Retinopathy

Blindness

5- Pathological Changes


Diabetic

Complication

• Diabetic Patients must examine feet

thoroughly, looking for blisters (بثور),

cuts (تخفيضات) and bruises (كدمات)

Diabetic Patients

Don't miss a spot

If you're unable to

see some parts of

your feet, use a

mirror.

Diabetes can damage nerves

(neuropathy), reducing the ability

to feel pain in your feet. That

means you may not notice a

small cut or blister until it

becomes a large sore.

Look for infection

• Athlete's foot is a common fungal infection

Serious Complications

Serious Complications of

Chronic hyperglycemia

Chronic hyperglycemiaGangrene of toes

Chronic hyperglycemia

Normal Diabetic retinopathy

Ophthalmoscope

Co

nti

nu

ou

s G

luco

se M

on

ito

r &

Insu

lin

Pu

mp

Insulin

pump

GLUCOSE MONITORING DEVICES

A device is now available for continuous

glucose measurement and continuous insulin

administration (i.e., a true artificial pancreas).

The MiniMed Continuous Glucose Monitoring

System (CGMS) measures glucose level every

five minutes for seventy-two hours and records

it in its internal memory.

http://www.minimed.com/doctors/md_products_cgms_ov_completepic.shtml

http://www.minimed.com/doctors/md_products_cgms_ov_completepic.shtml

Blood Sampling

GLUCOSE

MONITORIN

G DEVICES

Glucose Testing

GLUCOSE MONITORING DEVICES

Insulin pen injectors

Insulin jet injector

An insulin jet injector uses high-pressure air to send a fine

spray of insulin under your skin. This device may be an

option if you can't use needles....

INSULIN

DELIVERY

DEVICES

INSULIN DELIVERY DEVICES

INSULIN

DELIVERY

DEVICE

Site of Insulin Injection

Insulin is best injected into any area of

the body where fatty tissue is present

and where large blood vessels, nerves

and bones are not close to the surface .

Site of Insulin injection

Subcutaneous injection sites

INSULIN DELIVERY DEVICES

Spray Device (By Inhalation)

Thank You

9 blood glucose

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