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Slides current until 2008
Diagnosis, classification and prevention of diabetes
Section 1 | 1 of 4
Curriculum Module II–1 | Diagnosis, classification and presentation of diabetes
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Diagnosis and typesCurriculum Module II-1
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Definition of diabetes
Characterized by hyperglycaemia
• Defects in insulin production
• Autoimmune or other destruction of beta cells
• Insulin insensitivity
• Impaired action of insulin on target tissues
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Diagnosis and typesCurriculum Module II-1
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Definition of diabetes
Chronic hyperglycaemia associated with long-term damage to:
• Eyes
• Kidneys
• Nerves
• Heart and blood vessels
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Diagnosis and typesCurriculum Module II-1
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The diabetes epidemic
• 230 million affected in 2006
• 350 million within 20 years
• Most rapid in Indian and Asian subcontinents
IDF Diabetes Atlas
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Diagnosis and typesCurriculum Module II-1
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Classification
• Type 1 diabetes
–autoimmune
–LADA
–idiopathic
• Type 2 diabetes
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Diagnosis and typesCurriculum Module II-1
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Other specific types
• MODY
• Defects in insulin action
• Diseases of the pancreas
• Endocrine disorders
• Drug- or chemical-induced
• Infections
Classification
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Diagnosis and typesCurriculum Module II-1
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• Uncommon forms of immune-mediated diabetes
• Other genetic syndromes
• Gestational diabetes
Classification
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Diagnosis and typesCurriculum Module II-1
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Insulin
GluconeogenesisGlycogenolysisGlycogen synthesis
Glucose uptakeGlycogen synthesis
Blood glucose
Insulin and glucose disposal
Free fatty acid release
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Diagnosis and typesCurriculum Module II-1
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Glucose uptake Glycogenolysis Gluconeogenesis (amino acids) Ketone production (fatty acids)
Glucose uptake Protein degradation amino acids
Blood glucose
Insulin deficiency in type 1 diabetes
Triglyceride degradation fatty acids
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Diagnosis and typesCurriculum Module II-1
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Glucose uptake
Glycolysis
Gluconeogenesis (amino acids)
Glucose uptake Protein degradation amino acids
Blood glucose
Insulin insensitivity in ttype 2 diabetes
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Diagnosis and typesCurriculum Module II-1
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Blood glucose
Glucose uptake
Insensitivity to insulin inttype 2 diabetes
Glucose uptake
Glycolysis
Gluconeogenesis (amino acids)
Glucose uptake Protein degradation amino acids
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Diagnosis and typesCurriculum Module II-1
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Blood glucoseConverted to triglycerides
Effect of insulin resistance in ttype 2 diabetes
Glucose uptake
Glycolysis
Gluconeogenesis (amino acids)
Glucose uptake Protein degradation amino acids
Glucose uptake
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Diagnosis and typesCurriculum Module II-1
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Pathogenesis of type 1 diabetes
• Immunological activation
• Progressive beta-cell destruction
• Insufficient beta-cell function
• Dependent on exogenous insulin
• Risk of ketoacidosis
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Diagnosis and typesCurriculum Module II-1
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Pathogenesis of type 1 diabetes
• Genetic susceptibility
• Immune factors– other autoimmune disease– antigen-specific antibodies
• Environmental trigger– viruses– bovine serum albumin– nitrosamines: cured meats– chemicals: vacor (rat poison),
streptozotin
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Diagnosis and typesCurriculum Module II-1
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Beta-cell mass
Pathogenesis of type 1 diabetes
Time (months - years)
Trigger
Genetic
Pre-diabetes ‘Honeymoon’
Chronic phase
Clinical diabetes
Immunological abnormalities
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Diagnosis and typesCurriculum Module II-1
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Idiopathic type 1 diabetes
Non-autoimmune type 1 diabetes
• No autoimmune markers
• Permanent insulinopenia
• Ketoacidosis
• People of African and Asian origin
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Diagnosis and typesCurriculum Module II-1
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Epidemiology of type 1 diabetes
• Increasing in recent years
• Geographic variation
• Relative affluence
• Lack of treatment
IDF Diabetes Atlas
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Diagnosis and typesCurriculum Module II-1
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• Age of onset peaks
– preschool
– puberty
• Autumn/winter peaks
Epidemiology of type 1 diabetes
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Diagnosis and typesCurriculum Module II-1
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Type 2 diabetes
• 90%-95% of people with diabetes
• Insulin insensitivity and relative insulin deficiency
• Obesity or overweight
• Complications often present at diagnosis
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Diagnosis and typesCurriculum Module II-1
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Pathogenesis of type 2 diabetes
• Multiple genes involved
• Hyperinsulinaemia
• Poor fetal nutrition beta-cell formation
• Low birth weight/weight change
• “Thrifty gene”
• 7% beta-cell loss
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Diagnosis and typesCurriculum Module II-1
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Age (years)
Endogenous insulin
Insulin requirements
Beta-cell loss
The natural history of type 2 diabetes
Insulin requirements with age
Primary failure
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Diagnosis and typesCurriculum Module II-1
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Age (years)
Endogenous insulin
Insulin requirements
Beta-cell loss
Insulin insensitivity
Hyper-insulinaemia
The natural history of type 2 diabetes
Insulin requirements with age
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Diagnosis and typesCurriculum Module II-1
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Age (years)
Endogenous insulin
Insulin requirements
Secondary failure
The natural history of type 2 diabetes
Effect of oral drugs
Insulin requirements with age
Beta-cell loss
Hyper-insulinaemia
Insulin insensitivity
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Diagnosis and typesCurriculum Module II-1
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Epidemiology of type 2 diabetes
• Dramatic increase
• Aging population
• Disturbing trends parallel obesity epidemic
• Especially in adolescents and minority groups
• Increasing in young people
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Diagnosis and typesCurriculum 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?
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Diagnosis and typesCurriculum Module II-1
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Risk factors for type 2 diabetes
• 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
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Diagnosis and typesCurriculum Module II-1
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• Hypertension
• Dyslipidaemia
• Abdominal obesity
• Overweight
• Polycystic ovary disease
• Acanthosis nigricans
• Schizophrenia
Risk factors for type 2 diabetes
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Diagnosis and typesCurriculum Module II-1
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• Polydipsia
• Polyuria
• Nocturia
• Visual disturbance
• Fatigue
• Weight loss
• Infections
Signs and symptoms
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Diagnosis and typesCurriculum Module II-1
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Diagnosing diabetes
Normal Impaired fasting glucose*
Impaired glucose tolerance**
Diabetes
FPG <6.1mmol/L
<110mg/dL
6.1 to 6.9mmol/L*
110 to 126mg/dL
≥7.0mmol/L
≥126mg/dL
2hr PG <7.8mmol/L
<126mg/dL
7.8 to 11mmol/L**
126 to 200mg/dL
≥11.1mmol/L
≥200mg/dL
CDA 2003, ADA 2004, WHO 2002
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Diagnosis and typesCurriculum Module II-1
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Impaired glucose toleranceImpaired fasting glucose
• Intermediate states
• Increased risk of developing diabetes
• Prevention strategies to prevent or delay progression
• Increased risk of cardiovascular disease
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Diagnosis and typesCurriculum Module II-1
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Uncertain diagnosis:Oral glucose tolerance test
• 75 g glucose load after 8 hours fasting
• Readings taken in fasting state and at 1 and 2 hours
• Possible problems
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Diagnosis and typesCurriculum Module II-1
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• Urinary ketones
• Antibodies
• C-peptide
Tests for differential diagnosis
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Diagnosis and typesCurriculum Module II-1
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Metabolic syndrome
• 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
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Diagnosis and typesCurriculum Module II-1
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Prevention of type 1 diabetes
• Early exposure to cows milk protein
• Nicotinamide
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Diagnosis and typesCurriculum Module II-1
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Prevention of type 1 diabetes
Insulin
• Diabetes Prevention Trial
• Diabetes Prediction and Prevention Project
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Diagnosis and typesCurriculum Module II-1
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Prevention of type 2 diabetes
Lifestyle modification
• Da Qing Study
• Finnish Diabetes Prevention Study
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Diagnosis and typesCurriculum Module II-1
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Prevention of type 2 diabetes
Lifestyle vs medication
• Diabetes Prevention Program
• STOP-NIDDM
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Diagnosis and typesCurriculum Module II-1
Slide 38 of 48ACTIVITY
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?
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Diagnosis and typesCurriculum Module II-1
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Summary
Type 1 diabetes
• Results from progressive beta-cell destruction
• People with type 1 diabetes need insulin therapy to live
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Diagnosis and typesCurriculum Module II-1
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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
Summary
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Diagnosis and typesCurriculum Module II-1
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Review question
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
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Diagnosis and typesCurriculum Module II-1
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Review question
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
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Diagnosis and typesCurriculum Module II-1
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Review question
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
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Diagnosis and typesCurriculum Module II-1
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Review question
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
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Diagnosis and typesCurriculum Module II-1
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Answers
1. a
2. b
3. b
4. b
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References
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.
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Diagnosis and typesCurriculum Module II-1
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References
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.
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Diagnosis and typesCurriculum Module II-1
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References
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.