Diabetes

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Diabetes Mellitus in the year 2000
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Diabetes Mellitus in the year 2000
Report of the Expert Committee on the Diagnosis
and Classification of Diabetes Mellitus
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Diabetes Mellitus in the year 2000
Definition Description Classification Diagnosti
c criteria Testing for diabetes
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Definition
Diabetes Mellitus is a group of metabolic disease
characterized by hyperglycemia resulting from
defects in insulin secretion, insulin action, or
both. The chronic hyperglycemia of diabetes is
associated with log-term damage, dysfunction,
and failure of various organs, especially the
eyes, Kidneys, nerves, heart, and blood vessels.
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Description
Insulin deficiency Blood glucose Insulin
resistance
Symptoms Polyuria and polydipsia. Weight loss
with polyphagia. Blurred vision. Infection
susceptibility. DKA or NKHS.
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Types Stages
Stages
Hyperglycemia
Normal
Diabetes Mellitus Not Insulin Insulin
insulin requiring requiring requiring for
control for survival
Impaired Glucose Tolerance or Impaired Fasting
Glucose
Normal glucose regulation
Types
Type 1 Type 2 Other Specific Types
These patients can briefly return to normoglycemia
Vacor toxicity may require insulin for survival
Gestational Diabetes
Type 1 diabetes presenting in pregnancy may
require insulin for survival
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Hyperglycemia
Normal
Stage Aetiology
Diabetes Mellitus Not Insulin Insulin
insulin requiring requiring requiring for
control for survival
Impaired Glucose and / or fasting
hyperglycemia
Normal glucose tolerance ( achieved without
Pharmacological agents)
Aetiology
Islet cell destruction Autoimmune Idiopathic Pr
edominantly insulin resistance Predominantly
insulin secretory defects Other specific
disorders ( eg MODY, Endocrinopathies )
Type 1 diabetes
Type 2 diabetes
Other specific types of diabetes
Gestational Diabetes
Gestational diabetes
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Etiologic classification of diabetes mellitus
I- Type 1 diabetes
II- Type 2 diabetes.
III- Other specific types.
IV- Gestational diabetes mellitus.
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Etiologic classification of diabetes mellitus
I- Type 1 diabetes
A. Immune mediated Cellular-mediated
autoimmunity. Markers Islet cell
autoantibodies ( ICAs ). Autoantibodies to
insulin ( IAAs ). Autoantibodies to glutamic acid
decarboxylase ( GAD
). Autoantibodies to the tyrosine
phosphatase IA-2 and IA-2B. HLA HLA-DR/DQ
alleles can be either predisposing or protective.
T lymphocyte
B lymphocyte
Beta cell
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Etiologic classification of diabetes mellitus
I- Type 1 diabetes
Autoimmune destruction
Environmental Viral infection Obesity
Multiple genetic Graves disease Hashimotos
thyroiditis Addisons disease Vitiligo Pernicious
anemia
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Etiologic classification of diabetes mellitus
I- Type 1 diabetes
Presentation
Beta cell destruction Rapid infants and
children Slow adults Presentation DKA c
hildren and adolescents Hyperglycemia adults Hy
perglycemia to DKA Adults
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Etiologic classification of diabetes mellitus
I- Type 1 diabetes
B. Idiopathic No autoimmunity DKA Minor
ity of patients Strongly inherited No HLA
association Insulin requirement may come and go
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Etiologic classification of diabetes mellitus
II- Type 2 diabetes.

• Pathology
• Relative insulin deficiency ( initially).
• No Autoimmune destruction of ? -cell.
• Obesity ( insulin resistance ).
• No DKA (some times with stress ie infection).
• Pass undiagnosed.
• Macro- micro-vascular complications.
• Insulin is normal or high.

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Etiologic classification of diabetes mellitus
II- Type 2 diabetes.

• Pathology
• Relative insulin deficiency ( initially).
• No Autoimmune destruction of ? -cell.
• Obesity ( insulin resistance ).
• No DKA (some times with stress ie infection).
• Pass undiagnosed.
• Macro- micro-vascular complications.
• Insulin is normal or high.

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Etiologic classification of diabetes mellitus
II- Type 2 diabetes.

• Pathology
• Relative insulin deficiency ( initially).
• No Autoimmune destruction of ? -cell.
• Obesity ( insulin resistance ).
• No DKA (some times with stress ie infection).
• Pass undiagnosed.
• Macro- micro-vascular complications.
• Insulin is normal or high.

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Etiologic classification of diabetes mellitus
II- Type 2 diabetes.

• Pathology
• Relative insulin deficiency ( initially).
• No Autoimmune destruction of ? -cell.
• Obesity ( insulin resistance ).
• No DKA (some times with stress ie infection).
• Pass undiagnosed.
• Macro- micro-vascular complications.
• Insulin is normal or high.

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Etiologic classification of diabetes mellitus
II- Type 2 diabetes.

• Pathology
• Relative insulin deficiency ( initially).
• No Autoimmune destruction of ? -cell.
• Obesity ( insulin resistance ).
• No DKA (some times with stress ie infection).
• Pass undiagnosed.
• Macro- micro-vascular complications.
• Insulin is normal or high.

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Etiologic classification of diabetes mellitus
II- Type 2 diabetes.
Risk factors Age Obesity Lack of physical
activity Women H/O G.D.M Hypertension Dyslipi
demia Ethnic and racial subgroups Strong
genetic predisposition
Diabetes
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Etiologic classification of diabetes mellitus
III- Other specific types.
Genetic defects of ?-cell function Chromosome
12, HNF-1? (MODY3) Chromosome 7, glucokinase
(MODY2) Chromosome 20, HNF-4? (MODY1) Mitochondr
ial DNA Others Genetic defects in insulin
action Type A insulin resistance Leprechaunism
Rabson-Mendenhall syndrome Lipoatrophic
diabetes Others Disease of the exocrine
pancreas Pancreatitis Trauma/pancreatectomy Ne
oplasia Cystic fibrosis Hemochromatosis Fibroca
lculous pancreatopathy Others
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Etiologic classification of diabetes mellitus
III- Other specific types.
Endocrinopathies Acromegaly Cushings
syndrome Glucagonoma Pheochromocytoma Hyperthyr
oidism Somatostatinoma Aldosteronoma Others Dru
g or chemical-induced Vacor Dilantin Thiazides
Diazoxide Neoplasia Pentamidine ? -
interferon Nicotinic acid Cystic
fibrosis Glucocorticoids Thyroid
hormone Hemochromatosis ? -adrenergic
agonists Fibrocalculous pancreatopathy Others
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Etiologic classification of diabetes mellitus
III- Other specific types.
Infections Congenital rubella Cytomegalovirus
Others Uncommon forms of immune-mediated
diabetes Stiff-man syndrome Anti-insulin
receptor antibodies Others Other genetic
syndromes some times associated with
diabetes Downs syndrome Klinefelters Turner
s syndrome Wolframs syndrome Friedreichs
ataxia Huntingtons chorea Laurence-Moon-Biedl
syndrome Myotonic dystrophy Porphyria
Prader-Willi syndrome Others
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Etiologic classification of diabetes mellitus
IV- Gestational diabetes mellitus.
Definition Any degree of glucose intolerance
with onset or first recognition during
pregnancy. Prevalence - 1 14 of the total
pregnancies. - 90 of pregnancies complicated by
diabetes. Importance - Perinatal morbidity and
mortality - Maternal complications - Risk
factor for glucose intolerance
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Etiologic classification of diabetes mellitus
IV- Gestational diabetes mellitus.
Diagnostic criteria 1964 OSullivan and
Mahan 1979 NDDG (National Diabetes Data
Group) 1997 American Diabetes Associations
Fourth International Workshop-Conference on
Gestational Diabetes Mellitus.
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Etiologic classification of diabetes mellitus
IV- Gestational diabetes mellitus.
Screening
American Diabetes Associations (1997) fourth
international workshop-conference on gestational
diabetes recommendations
Screen all pregnant women ( 24-28 weeks of
gestation )
Including High risk group Marked obesity H/O
GDM Glycosuria Strong FH
Including Average risk group
Excluding Low risk group lt 25 years of
age Normal body weight - ve family history - ve
H/O abn. glucose metabolism H/O poor obstetric
outcome Ethnic group of low diabetes risk
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Etiologic classification of diabetes mellitus
IV- Gestational diabetes mellitus.
Screening
American Diabetes Associations (1997) fourth
international workshop-conference on gestational
diabetes recommendations
Low risk group No screening Average risk
group Two step approach High risk group One
step approach
Glucose Challenge Test GCT ( 50 gm oral glucose
load ) Glucose after 1hr ? Oral Glucose
Tolerance Test OGTT 75 or 100 FBS, 1hr, 2hrs
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Etiologic classification of diabetes mellitus
IV- Gestational diabetes mellitus.
Screening
American Diabetes Associations (1997) fourth
international workshop-conference on gestational
diabetes recommendations
Low risk group No screening Average risk
group Two step approach High risk group One
step approach
Oral Glucose Tolerance Test OGTT 75 or 100 FBS,
1hr, 2hrs
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Etiologic classification of diabetes mellitus
IV- Gestational diabetes mellitus.
Diagnostic criteria
100-g Glucose load
mg/dl mmol/l Fasting 95 5.3 1-h 180 10.0
2-h 155 8.6 3-h 140 7.8
75-g Glucose load
mg/dl mmol/l Fasting 95 5.3 1-h 180 10.0
2-h 155 8.6
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Etiologic classification of diabetes mellitus
Impaired glucose tolerance IGT Impaired fasting
glucose IFG
Normal
Diabetic
IGT IGF
IGT WHO criteria IGF FPG 110 - 126
mg/dL 6.1 - 7.0 mmol/L
Why
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Etiologic classification of diabetes mellitus
Impaired glucose tolerance IGT Impaired fasting
glucose IFG
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Etiologic classification of diabetes mellitus
Impaired glucose tolerance IGT Impaired fasting
glucose IFG

• They are known risk factors for future diabetes
  and
• cardiovascular disease.
• Intermediate stage for all types of diabetes.
• Associated with insulin resistance syndrome or
• Syndrome X
• Insulin resistance
• Hyperinsulinemia
• Obesity
• Dyslipidemia ( high triglyceride and/or low HDL
  )
• Hypertension

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Etiologic classification of diabetes mellitus
Diagnostic criteria for diabetes mellitus The new
criteria
Symptoms of diabetes ( polyuria, polydepsia,
and weight loss ) Random Blood Sugar ( RBS )
casual plasma glucose or gt 200 mg/dL (
11.1 mmol/L )
1 2 3
Fasting plasma glucose ( FPG ) at least 8hours
fast or gt 126 mg/dL ( 7.0 mmol/L )
Two hours plasma glucose (2PG ) after 75
anhydrous glucose in water or gt 200 mg/dL (
11.1 mmol/L )
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Etiologic classification of diabetes mellitus
Impaired fasting glucose IFG

• For epidemiological studies FPG is
• standardization
• Facilitation
• Cheep
• Diagnosis New criteria? WHO criteria?
• mg/dL mmol/L mg/dL mmol/L
• Normal lt110 lt6.1 lt 140
  lt 7.8
• IFG / IGT 110 - lt126 6.1- lt 7.0
  140 - lt 200 7.8 - lt11.1
• ? DM or gt 126 or gt 7.0
  or gt 200 or gt 11.1

? 8 hours over night fast. ? 2 hours post 75 gm
glucose load.
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Etiologic classification of diabetes mellitus
Old and new diagnostic criteria
The criteria New case Diabetes
Discovered Prevalence Known cases
No 7.92 WHO criteria 6.34
14.26 New criteria 4.35 12.27
- 1.99 14
The new criteria will lead to 14 ( slightly )
lower estimates of diabetes prevalence.
Data from NHANES III for individuals 40-74 years
old.
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Etiologic classification of diabetes mellitus
Testing healthy individuals
Type 1 diabetes More than one antibodies (
ICA, IAA, GAD, IA-2 ) No effective method can
prevent or delay the disease Screening is not
cost-effective Type 2 diabetes 50 of
type 2 are undiagnosed Chronic complications
precede diabetes ( Retinopathy 7 years ) Risk
factors
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Etiologic classification of diabetes mellitus
HbA1c
Not recommended for diagnosis of diabetes, but
valuable for glycemic control of diabetes.
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Etiologic classification of diabetes mellitus
Criteria for testing asymptomatic individuals

• All individual above 45 years of age every 3
  years
• Any individual with
• ? Obese ( gt 120 desirable weight or BMI gt 27
  ).
• ? ve F/H first degree relatives.
• ? High risk ethnic population.
• ? H/O GDM or big baby ( gt 9 lb ).
• ? Hypertension gt 140/90
• ? HDL lt 35mg/dl ( 0.9 mmol/l )
• ? Triglyceride gt 250mg/dl ( 2.82 mmol/l )
• ? Known to have IGT or IFG