Facts about Type I

Diabetes Mellitus

“ Diabetes was long thought to be a kidney disease

(Greek & Arabic Methodology).

“ Thomas Willis (1621 - 1679), discovered the

sweetness of urine, hence, the name Diabetes Mellitus

arised”

“Mathew Dobson (1776), identified glycosuria.

“Claude Bernard and Von Mering (1889), discovered in

the same year that pancreatectomy causes

diabetes”

“Fredrick Banting (1921), successfully, extracted

insulin, gaining the Nobel prize for this great

discovery”.

“Leonard Thompson (14 year old boy) & Elizabeth Hughes (aged

14 years), were the first patients to be treated with insulin in

1922.

Dear Mom, ..I look entirely different gaining

every hour strength & weight..

..it is truly miraculous....I wish you could see the expression

on there faces, they are so astounded in my unheard of

progress..Leonard,

April, 1922

Insulin Secretion•Site : B cells (Pancreatic Islets of

Langerhan’s).•Mechanism : from secretory

granules of Proinsulin (in the Golgi complex of B cells).

•Factors Related : glucose, gut hormones, A. As., F.As., ketone

bodies, nerve supply& glucagon.

Insulin Secretion

INSULIN SECRETION

GLUCOSE GKG-6-P

PK

PYRUVATES

ATP

Ca2+DEPOLARIZATION

++ +

__

_

K +

INSULIN

Glu t2

Blood Glucose

Biphasic Glucose Stimulation

1st phase: Rapid onset (with peak level after 1-2 minutes) & Short duration.

2nd phase:Delayed onset & Longer duration.

Insulin Secretion Curve

Biphasic insulin response to a constant glucose stimulation(IVGTT - hyperglycemic Clamp)

Insulin rate

Time (min)

Basal

4 60

Response to I.V. Glucose

Insulin Mechanism of action

Carbohydrate metabolismLipid metabolismProtein metabolism

Insulin Receptors

•Receptor-mediated endocytosis.•Gene transcription.•Glucose transporters.

Insulin Receptors

Insulin Hypoglycemic Action

Glucose storage .. Anabolic effect & Anticatabolic effect .

Insulin Lack

Insulin Deficiency

Insulin Defect Complications

Sorbitol Pathway

Diabetes Mellitus

“A metabolic disorder, with high risk of complications &

chronic hyperglycemia (with or without glycosuria).“

Prevalence of Insulin Disorders

“The prevalence worldwide varies from 2-5% in developing countries, to 5-10% in

developed countries.”

N.B. ( A cross-sectional study revealed incidence of 7million cases in the Egyptian

population at the year of 1992).

Diabetes: Clinical Features•Symptoms:

–Polyuria–Polydypsia=thirst–Polyphagia=appetite–Asthenia & Loss of weight

•Signs:

No specific signs may besigns of complications

•Signs:

No specific signs may be signs of complications

Stage/Test Fasting Plasma Glucose (FPG)

(Preferred)

Casual Plasma Glucose

Oral Glucose Tolerance Test

(OGTT)

Diabetes FPG > 126 mg/dL

(7.0 mmol/L)

Casual Plasma Glucose > 200

mg/dL (11.1 mmol/L) plus symptoms.

Two-hour Plasma (2hPG) >200 mg/dl

Impaired Glucose Homeostasis

Impaired Fasting Glucose

(IFG) = FPG > 110 and <126

mg/dl

Impaired glucose Tolerance (IGT) =

2hPG>140mg/dl and <200 mg/dL

Normal FPG< 110 mg/dL 2hPG<140 md/dl

Diagnosis of D. Mellitus

American Diabetes Association

Investigation of Diabetes

•Fasting Blood Glucose level

•Post prandial blood glucose level

•Glycosuria

•Glycosylated haemoglobin.

Glycosylated Haemoglobin

•Hb + G = HbA1 (non reversible)

•In hyperglycemia up to 20% or more.

•Occurs in the active life span of the RBCs.

•Gives information about the state of BGL

•during the previous 2 months.

Predisposing FactorsIDDM

•Heredity.•Histocomptability.•Virus infection.•Sesonality.•Cell-mediated immunity.

Seasonality

Stages of IDDM development

Age and insulin content