t2d concepts

8/3/2019 T2D Concepts

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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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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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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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