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Diagnosis, classification and
prevention of diabetes
Diagnosis and types
Definition of diabetes
Curriculum Module II-1
Slide 2 of 48
Characterized by hyperglycaemia
• Defects in insulin production
• Autoimmune or other
destruction of beta cells
• Insulin insensitivity
• Impaired action of insulin on
target tissues
Slides current until 2008
Diagnosis and types
Definition of diabetes
Curriculum Module II-1
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Chronic hyperglycaemia associated
with long-term damage to:
• Eyes
• Kidneys
• Nerves
• Heart and blood vessels
Slides current until 2008
Diagnosis and types
The diabetes epidemic
Curriculum Module II-1
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• 230 million affected in 2006
• 350 million within 20 years
• Most rapid in Indian and Asian
subcontinents
IDF Diabetes Atlas
Slides current until 2008
Diagnosis and types
Classification
Curriculum Module II-1
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• Type 1 diabetes
– autoimmune
– LADA
– idiopathic
• Type 2 diabetes
Slides current until 2008
Diagnosis and types
Curriculum Module II-1
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Classification
Other specific types
• MODY
• Defects in insulin action
• Diseases of the pancreas
• Endocrine disorders
• Drug- or chemical-induced
• Infections
Slides current until 2008
Diagnosis and types
Classification
Curriculum Module II-1
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• Uncommon forms of immunemediated diabetes
• Other genetic syndromes
• Gestational diabetes
Slides current until 2008
Diagnosis and types
Insulin and glucose disposal
Curriculum Module II-1
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Gluconeogenesis
Glycogenolysis
Glycogen synthesis
Insulin
Blood glucose
Glycogen
synthesis
Glucose uptake
Free fatty acid release
Slides current until 2008
Diagnosis and types
Insulin deficiency in
type 1 diabetes
Curriculum Module II-1
Slide 9 of 48
Glucose uptake
Glycogenolysis
Gluconeogenesis (amino acids)
Ketone production (fatty acids)
Blood glucose
Glucose uptake
Protein degradation  amino acids
Triglyceride degradation  fatty acids
Slides current until 2008
Diagnosis and types
Curriculum Module II-1
Slide 10 of 48
Insulin insensitivity in
type 2 diabetes
Glucose uptake
Glycolysis
Gluconeogenesis (amino acids)
Blood glucose
Glucose uptake
Protein degradation  amino acids
Slides current until 2008
Diagnosis and types
Curriculum Module II-1
Slide 11 of 48
Insensitivity to insulin in
type 2 diabetes
Glucose uptake
Glycolysis
Gluconeogenesis (amino acids)
Blood glucose
Glucose uptake
Protein degradation  amino acids
Glucose uptake
Slides current until 2008
Diagnosis and types
Effect of insulin resistance in
type 2 diabetes
Curriculum Module II-1
Slide 12 of 48
Glucose uptake
Glycolysis
Gluconeogenesis (amino acids)
Blood glucose
Converted to triglycerides
Glucose uptake
Protein degradation  amino acids
Glucose uptake
Slides current until 2008
Diagnosis and types
Pathogenesis of type 1 diabetes
Curriculum Module II-1
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• Immunological activation
• Progressive beta-cell destruction
• Insufficient beta-cell function
• Dependent on exogenous insulin
• Risk of ketoacidosis
Slides current until 2008
Diagnosis and types
Pathogenesis of type 1 diabetes
Curriculum Module II-1
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• Genetic susceptibility
• Immune factors
– other autoimmune disease
– antigen-specific antibodies
• Environmental trigger
– viruses
– bovine serum albumin
– nitrosamines: cured meats
– chemicals: vacor (rat poison),
streptozotin
Slides current until 2008
Diagnosis and types
Curriculum Module II-1
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Pathogenesis of type 1 diabetes
Trigger
Genetic
Immunological
abnormalities
Beta-cell
mass
Clinical
diabetes
Pre-diabetes
‘Honeymoon’
Chronic
phase
Time (months - years)
Slides current until 2008
Diagnosis and types
Idiopathic type 1 diabetes
Curriculum Module II-1
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Non-autoimmune type 1 diabetes
• No autoimmune markers
• Permanent insulinopenia
• Ketoacidosis
• People of African and Asian origin
Slides current until 2008
Diagnosis and types
Curriculum Module II-1
Slide 17 of 48
Epidemiology of type 1 diabetes
• Increasing in recent years
• Geographic variation
• Relative affluence
• Lack of treatment
IDF Diabetes Atlas
Slides current until 2008
Diagnosis and types
Epidemiology of type 1 diabetes
Curriculum Module II-1
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• Age of onset peaks
– preschool
– puberty
• Autumn/winter peaks
Slides current until 2008
Diagnosis and types
Type 2 diabetes
Curriculum Module II-1
Slide 19 of 48
• 90%-95% of people with
diabetes
• Insulin insensitivity and
relative insulin deficiency
• Obesity or overweight
• Complications often present
at diagnosis
Slides current until 2008
Diagnosis and types
Pathogenesis of type 2 diabetes
Curriculum Module II-1
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• Multiple genes involved
• Hyperinsulinaemia
• Poor fetal nutrition   beta-cell
formation
• Low birth weight/weight change
• “Thrifty gene”
• 7% beta-cell loss
Slides current until 2008
Diagnosis and types
Curriculum Module II-1
Slide 21 of 48
The natural history of
type 2 diabetes
Beta-cell loss
Primary
failure
Insulin
requirements
 Insulin
requirements
with age
Endogenous
insulin
Age (years)
Slides current until 2008
Diagnosis and types
The natural history of
type 2 diabetes
Curriculum Module II-1
Slide 22 of 48
Beta-cell loss
 Insulin
requirements
with age
Hyperinsulinaemia
Insulin
requirements
Insulin
insensitivity
Endogenous
insulin
Age (years)
Slides current until 2008
Diagnosis and types
Curriculum Module II-1
Slide 23 of 48
The natural history of
type 2 diabetes
Beta-cell loss
Hyperinsulinaemia
Insulin
requirements
Secondary
failure
Effect of
oral drugs
Insulin
insensitivity
 Insulin
requirements
with age
Endogenous
insulin
Age (years)
Slides current until 2008
Diagnosis and types
Epidemiology of type 2 diabetes
Curriculum Module II-1
Slide 24 of 48
• Dramatic increase
• Aging population
• Disturbing trends parallel obesity
epidemic
• Especially in adolescents and
minority groups
• Increasing in young people
Slides current until 2008
ACTIVITY
Diagnosis and types
Curriculum Module II-1
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• What are the most common risk
factors for type 2 diabetes for
people in your country?
• Are any of these risk factors
modifiable?
Slides current until 2008
Diagnosis and types
Risk factors for type 2 diabetes
Curriculum Module II-1
Slide 26 of 48
• Age > 40 years
• First-degree relative with diabetes
• Member of high risk population
• History of impaired glucose tolerance,
impaired fasting glucose
• Vascular disease
• History of gestational diabetes
• History of delivery of macrosomic
baby
CDA 2003
Slides current until 2008
Diagnosis and types
Risk factors for type 2 diabetes
Curriculum Module II-1
Slide 27 of 48
• Hypertension
• Dyslipidaemia
• Abdominal obesity
• Overweight
• Polycystic ovary disease
• Acanthosis nigricans
• Schizophrenia
Slides current until 2008
Diagnosis and types
Signs and symptoms
Curriculum Module II-1
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• Polydipsia
• Polyuria
• Nocturia
• Visual disturbance
• Fatigue
• Weight loss
• Infections
Slides current until 2008
Diagnosis and types
Curriculum Module II-1
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Diagnosing diabetes
Normal
Impaired fasting glucose*
Diabetes
Impaired glucose
tolerance**
FPG
<6.1mmol/L
6.1 to 6.9mmol/L*
≥7.0mmol/L
<110mg/dL
110 to 126mg/dL
≥126mg/dL
2hr PG <7.8mmol/L
7.8 to 11mmol/L**
≥11.1mmol/L
<126mg/dL
126 to 200mg/dL
≥200mg/dL
CDA 2003, ADA 2004, WHO 2002
Slides current until 2008
Diagnosis and types
Table 2—Criteria for the diagnosis of diabetes
Curriculum Module II-1
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1. A1C 6.5%. The test should be performed in a laboratory using a
method
that is NGSP certified and standardized to the DCCT assay.*
OR
2. FPG 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for
at least 8 h.
OR
3. Two-hour plasma glucose 200 mg/dl (11.1 mmol/l) during an OGTT.
The test should be performed as described by the World Health
Organization, using a glucose load containing the equivalent of 75 g
anhydrous glucose dissolved in water.*
OR
4. In a patient with classic symptoms of hyperglycemia or hyperglycemic
crisis, a random plasma glucose 200 mg/dl (11.1 mmol/l).
*In the absence of unequivocal hyperglycemia, criteria 1–3 should be
confirmed by repeat testing.
ADA 2010 Guideline
Diagnosis and types
Impaired glucose tolerance
Impaired fasting glucose
Curriculum Module II-1
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• Intermediate states
• Increased risk of developing
diabetes
• Prevention strategies to prevent
or delay progression
• Increased risk of cardiovascular
disease
Slides current until 2008
Diagnosis and types
Uncertain diagnosis:
Oral glucose tolerance test
Curriculum Module II-1
Slide 32 of 48
• 75 g glucose load after 8 hours
fasting
• Readings taken in fasting state
and at 1 and 2 hours
• Possible problems
Slides current until 2008
Diagnosis and types
Tests for differential diagnosis
Curriculum Module II-1
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• Urinary ketones
• Antibodies
• C-peptide
Slides current until 2008
Diagnosis and types
Metabolic syndrome
Curriculum Module II-1
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• Cluster of risk factors or syndrome
• Type 2 diabetes
• Different criteria
• Three-fold increase in heart
disease and stroke
• Two-fold increase in cardiovascular
disease deaths
Slides current until 2008
Diagnosis and types
Prevention of type 1 diabetes
Curriculum Module II-1
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• Early exposure to cows milk
protein
• Nicotinamide
Slides current until 2008
Diagnosis and types
Prevention of type 1 diabetes
Curriculum Module II-1
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Insulin
• Diabetes Prevention Trial
• Diabetes Prediction and
Prevention Project
Slides current until 2008
Diagnosis and types
Prevention of type 2 diabetes
Curriculum Module II-1
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Lifestyle modification
• Da Qing Study
• Finnish Diabetes Prevention Study
Slides current until 2008
Diagnosis and types
Prevention of type 2 diabetes
Curriculum Module II-1
Slide 38 of 48
Lifestyle vs medication
• Diabetes Prevention Program
• STOP-NIDDM
Slides current until 2008
ACTIVITY
Diagnosis and types
Curriculum Module II-1
Slide 39 of 48
Type 2 diabetes can be delayed in
people with IGT
Lifestyle modification is most
effective
What do you think could be done at
community level to prevent or delay
diabetes?
Slides current until 2008
Diagnosis and types
Curriculum Module II-1
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Summary
Type 1 diabetes
• Results from progressive betacell destruction
• People with type 1 diabetes need
insulin therapy to live
Slides current until 2008
Diagnosis and types
Curriculum Module II-1
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Summary
Type 2 diabetes
• Often characterized by insulin
insensitivity and relative rather
than absolute insulin deficiency
• A progressive condition
• Most people with type 2 diabetes
will need insulin within 5 to 10
years of diagnosis
Slides current until 2008
Diagnosis and types
Review question
Curriculum Module II-1
Slide 42 of 48
1. The pathogenesis for type 2 diabetes
includes:
a. Insulin deficiency and insulin
insensitivity
b. Insensitivity to insulin and
autoimmune beta-cell destruction
c. Autoimmune beta-cell destruction
and glucagon deficiency
d. Insulin deficiency and glucagon
deficiency
Slides current until 2008
Diagnosis and types
Review question
Curriculum Module II-1
Slide 43 of 48
2. A person with type 2 diabetes, recently
started on insulin, asks if there is a way
to measure if he/she is still producing any
insulin. The correct response would be:
a. Islet cell antibody tests
b. C-peptide test
c. HbA1c test
d. Serum insulin test
Slides current until 2008
Diagnosis and types
Review question
Curriculum Module II-1
Slide 44 of 48
3. The Diabetes Prevention Program (DPP):
a. Included people with type 1
diabetes
b. Included only people with IGT
c. Tested the value of exercise
d. Included people with type 2
diabetes
Slides current until 2008
Diagnosis and types
Review question
Curriculum Module II-1
Slide 45 of 48
4. Type 1 diabetes is usually caused by:
a. Injury to the pancreas
b. An autoimmune reaction
c. Insulin insensitivity in the cells
d. Hypersensitivity to insulin
Slides current until 2008
Diagnosis and types
Curriculum Module II-1
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Answers
1. a
2. b
3. b
4. b
Slides current until 2008
Diagnosis and types
References
Curriculum Module II-1
Slide 47 of 48
1.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes
Care 2004; 27(suppl 1): S5-S10.
2.
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian
Diabetes Association 2003 clinical practice guidelines for the prevention and management of
diabetes in Canada. Can J Diab 2003; 27(suppl 2).
3.
Chiasson JL, Josse RG, Gomis R, et al. Acarbose for prevention of type 2 diabetes mellitus:
The STOP-NIDDM randomized trial. Lancet 2002; 346: 393-403.
4.
Delahanty LM and Halford BN. The role of Diet Behaviours in Achieving improved glycaemic
control in intensively treated patients in the Diabetes Control and Complications Trial.
Diabetes Care 1993; 16(11): 1453-58.
5.
Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes
treatment on the development and progression of long-term complications in adolescents with
insulin dependent diabetes mellitus: Diabetes Control and Complications Trial. The Journal of
Paediatrics 1994; 125(2): 177-88.
6.
Diabetes Control and Complications Trial/epidemiology of diabetes interventions and
complications research group intensive diabetes therapy and carotid intima-media thickness in
type 1 diabetes mellitus. New Engl J Med 2003; 348: 2294-303.
7.
Diabetes Control and Complications Trial: The effect of intensive treatment of diabetes on the
development and progression of long-term complications in insulin-dependent diabetes
mellitus. N Engl J Med 1993; 329: 977-86.
Slides current until 2008
Diagnosis and types
References
Curriculum Module II-1
Slide 48 of 48
8.
Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults:
findings from the third National Health and Nutrition Examination Survey. JAMA 2002; 297:
356-59.
9.
Diabetes Atlas 2006. Brussels: International Diabetes Federation, 2006.
10.
Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with
the metabolic syndrome. Diabetes Care 2001; 24(4): 683-9.
11.
Pan X, Li G, Hu Y, et al. Effects of diet and exercise in preventing NIDDM in people with
impaired glucose tolerance: The Da Qing IGT and Diabetes Study. Diabetes Care 1997; 20(4):
537-44.
12.
Report of a WHO Consultation. Laboratory Diagnosis and monitoring of Diabetes Mellitus.
World Health Organisation 2002. http://whqlibdoc.who.int/hq/2002/9241590483.pdf cited
April 30, 2005.
13.
Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by
changes in lifestyle among subjects with impaired glucose tolerance. N Eng J Med 2001; 344:
1343-50.
14.
The Diabetes Prevention Program Research Group. The diabetes prevention Program (DPP).
Diabetes Care 2002; 23(12): 2165-71.
15.
UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulpfonylureas or
insulin compared with conventional treatment and risk of complications in patients with type 2
diabetes. Lancet 1998; 352: 837-53.
Slides current until 2008
Diagnosis and types
References
Curriculum Module II-1
Slide 49 of 48
16.
UK Prospective Diabetes Study Group. Tight blood pressure control and risk of
macrovascular and microvascular complications in type 2 diabetes UKPDS 38. BMJ
1998; 317: 703-13.
17.
IDF Clinical Guidelines Task Force. Global Guideline for Type 2 Diabetes. Brussels:
International Diabetes Federation, 2005.
18.
Harris SB, Ekoe JM, Zdanowicz Y, Webster-Bogaert S. Glycemic Control and
morbidity in the Canadian primary care setting (results of the diabetes in Canada
evaluation study). Diab Research and Clin Pract 2005; 70: 90-7.
Slides current until 2008