Transcript
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Concepts in the natural history ofdiabetes.
Dr H Oosthuizen
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Pathogenesis of Type 1 diabetes.Autoimmune Type 1 Diabetes
Beta cells destroyed via autoimmune mechanism.
Genetically predisposed people:triggering factor
= production of islet cell Ab.
Islet cell Abdestroy Beta cells.
Insulin production decreases.
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Pathogenesis of Type 1 diabetes.Autoimmune Type 1 Diabetes
Viruses + other environmental agents havebeen shown to be triggering factors.
Viruses can damage beta cells by:
1.Direct invasion.2.Triggering an auto
immune response.
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Pathogenesis of Type 1 diabetes.Autoimmune Type 1 Diabetes
Implicated viruses:
mumps, intrauterine rubella, coxsackie Bvirus, echo virus, gytomegalo virus andherpes virus.
Chemical substances that reduce diabetes:alloxan, streptozotosin and dietarynitroamides.
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Pathogenesis of Type 1 diabetes.Idiopathic Type 1 Diabetes
No known aetiology.
Permanent insulinopaenia.
This form is strongly inherited.
Not HLA associated.
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Clinical features of Type 1
diabetes. Presents acutely. Symptoms due to
hyperglycaemia(thirst, polyuria, tiredness,weight loss).
Ketone production - abdominal pain, nausea and
vomiting.
Other symptoms: blurred vision, repeated
infections. No chronic complications at diagnosis, may
only be apparent 5-10 years post diagnosis.
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Incidence of Type 1 diabetes. Incidence peaks at 11-13 years.
Seasonal variation: lowest rates in spring
and summer.
Geographical variation: Japan has a very
low incidence.
10% of Type 1 diabetics are over 65 years
of age.
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Type 2 diabetes. Patients frequently undiagnosed for many
years.
May present with hyperglycaemia
symptoms.
Coma is rare in type 2 diabetes.
May progress to an absolute state of insulin
deficiency.
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Pathogenesis of Type 2 diabetes. Cause:a combination of impaired insulin secretion and
insensitivity of target tissues to insulin.
Impaired insulin secretion due to beta cell malfunctioncan be associated with:
1. Incorrect secretion pattern.
2. Ratio of proinsulin to insulin.
3. Amyloid deposits.
4. Slow destruction of beta cells
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Mechanisms for insulin
resistance.1. Receptor numbers are decreased. (Often
seen in obese and aged patients.)
2. Receptor structure is abnormal.
3. Insulin resistance at post receptorevents.
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Clinical features of Type 2
diabetes. Diagnosis due to presence of
complications.(At least 30% patients havecomplications at diagnosis).
Symptoms are mild, gradual onset. Classicdiabetic symptoms may be present.
Type 2 diabetics are usually:
over 40 years, fat (apple obesity) and no
ketones are present.
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Insulin Secretion in Non-Diabetics
and Type 2 Diabetics
Clock Time (Hours)06:00
Normal
Type 2 DM
10:00 14:00 18:00 22:00 02:00 06:00
800
700
600
500
400
300
200
100Insu
linSecretion(pmol/min)
O'MEARA et al. Am. J. Medicine, 1990;89
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Glucose Contributions to HbA1c
+
Postprandial Glucose,Influenced by:
Preprandial glucose
Glucose load from meal
Insulin secretion
Insulin sensitivity in peripheraltissues and liver
Fasting Glucose,Influenced by:
Hepatic glucoseproduction
Hepatic sensitivity toinsulin
HbA1c =
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Postprandial glucose Most of the day may be postprandial
HbA1c = FPG + PPG
Postprandial from the time glucose starts torise until it comes down again
Time period up to 2.5 h after a meal
normal individuals 1.5 h Testing of PPG recommended 2h after the
start of a meal
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Hyperglycemic"Peaks"
Fasting/Preprandialglucose elevations
Acute toxicity Chronic toxicity
Tissue lesion
Complications
Overall Glycemic Control (HbA1c)
Possible Pathogenesis of Diabetic
Complications
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Which glucose variable? Fasting plasma glucose (FPG), postprandial plasma
glucose (PPG) and HbA1c all have pros and cons
Where feasible, HbA1c
should be the standard
measurement by which to gauge risk and treatment
efficacy
FPG and PPG are useful
to adjust daily treatment
to monitor for hypoglycaemia
for confirmation as haemoglobin metabolism problems
may mask true HbA1c levels
if there is a lack of resources for HbA1c measurement
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Link Between Obesity and Type 2 Diabetes:Nurses Health Study
Colditz GA, et al. Ann Intern Med. 1995;122:481-486.
0
20
40
60
80
100
120
< 22 22-
22.9
23-
23.8
24-
24.9
25-
26.9
27-
28.9
29-
30.9
31-
32.9
33-
34.9
> 35
BMI (kg/m2)
Age-AdjustedRe
lativeRisk
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EVERY 1%
reduction in HBA1CREDUCED
RISK*
1%
Deaths from diabetes
Heart attacks
Microvascularcomplications
Peripheral vasculardisorders
UKPDS 35. BMJ 2000; 321: 405-12
Lessons from UKPDS:
Better control means fewer complications
*p
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