diabetes mellitus in the year 2000. diabetes mellitus in the year 2000 report of the expert...
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Diabetes Mellitus
in the year2000
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DiabetesMellitus
in the year2000
Report of the Expert Committee on
the Diagnosis and Classificationof
Diabetes Mellitus
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DiabetesMellitus
in the year2000
Definition
Description
Classification
Diagnostic criteria
Testing for diabetes
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DefinitionDiabetes 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
Type 1
Type 2
Other SpecificTypes
Diabetes MellitusNot Insulin Insulin insulin requiring requiring
requiring for control for survival
Impaired Glucose Toleranceor
Impaired Fasting Glucose
Normalglucose
regulation
These patients can briefly return to normoglycemia
Type 1 diabetes presenting in pregnancy may require insulin for survival
HyperglycemiaNormal
Stages
Types
Gestational Diabetes
Vacor toxicity may require insulin for survival
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Stage&
Aetiology
Islet cell destruction:AutoimmuneIdiopathic
Predominantly insulinresistancePredominantly insulin secretorydefects
Other specific disorders( eg MODY, Endocrinopathies )
Diabetes Mellitus
Not Insulin Insulin insulin requiring requiring
requiring for control for survival
Impaired Glucoseand / or fasting hyperglycemia
Normal glucosetolerance
( achieved without Pharmacological agents)
HyperglycemiaNormal
Aetiology
Gestational Diabetes
Type 2 diabetes
Other specific types of diabetes
Gestational diabetes
Type 1 diabetes
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Etiologicclassification
of
diabetesmellitus
II- Type 2 diabetes.
III- Other specific types.
IV- Gestational diabetes mellitus.
I- Type 1 diabetes:
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Etiologicclassification
of
diabetesmellitus
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 eitherpredisposing or protective. Beta cell
B lymphocyte T lymphocyte
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Etiologicclassification
of
diabetesmellitus
I- Type 1 diabetes:
Multiple genetic:
Graves’ diseaseHashimoto’s thyroiditisAddison’s diseaseVitiligoPernicious anemia
Autoimmune destruction
Environmental:
Viral infectionObesity
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Etiologicclassification
of
diabetesmellitus
I- Type 1 diabetes:
Beta cell destruction:
Rapid infants and childrenSlow adults
Presentation:
DKA children and adolescentsHyperglycemia adultsHyperglycemia to DKA Adults
Presentation
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Etiologicclassification
of
diabetesmellitus
I- Type 1 diabetes:
B. Idiopathic:
No autoimmunityDKAMinority of patientsStrongly inheritedNo HLA associationInsulin requirement may come and go
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Etiologicclassification
of
diabetesmellitus
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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Etiologicclassification
of
diabetesmellitus
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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Etiologicclassification
of
diabetesmellitus
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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Etiologicclassification
of
diabetesmellitus
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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Etiologicclassification
of
diabetesmellitus
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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Etiologicclassification
of
diabetesmellitus
II- Type 2 diabetes.
Risk factors:
AgeObesityLack of physical activity
WomenH/O G.D.MHypertensionDyslipidemiaEthnic and racial subgroupsStrong genetic predisposition
Diabetes
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Etiologicclassification
of
diabetesmellitus
III- Other specific types.
Genetic defects of -cell function:Chromosome 12, HNF-1 (MODY3)Chromosome 7, glucokinase (MODY2)Chromosome 20, HNF-4 (MODY1)Mitochondrial DNAOthers
Genetic defects in insulin action:Type A insulin resistanceLeprechaunismRabson-Mendenhall syndromeLipoatrophic diabetesOthers
Disease of the exocrine pancreas:PancreatitisTrauma/pancreatectomyNeoplasiaCystic fibrosisHemochromatosisFibrocalculous pancreatopathyOthers
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Etiologicclassification
of
diabetesmellitus
III- Other specific types.
Endocrinopathies:AcromegalyCushing’s syndromeGlucagonomaPheochromocytomaHyperthyroidismSomatostatinomaAldosteronomaOthers
Drug or chemical-induced:VacorDilantinThiazidesDiazoxideNeoplasiaPentamidine - interferonNicotinic acidCystic fibrosisGlucocorticoidsThyroid hormoneHemochromatosis -adrenergic agonistsFibrocalculous pancreatopathyOthers
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Etiologicclassification
of
diabetesmellitus
III- Other specific types.
Infections:Congenital rubellaCytomegalovirusOthers
Uncommon forms of immune-mediated diabetes:“ Stiff-man “ syndromeAnti-insulin receptor antibodiesOthers
Other genetic syndromes some times associated with diabetes:Down’s syndromeKlinefelter’sTurner’s syndromeWolfram’s syndromeFriedreich’s ataxiaHuntington’s choreaLaurence-Moon-Biedl syndromeMyotonic dystrophyPorphyria Prader-Willi syndrome Others
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Etiologicclassification
of
diabetesmellitus
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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Etiologicclassification
of
diabetesmellitus
IV- Gestational diabetes mellitus.
Diagnostic criteria:
1964 O’Sullivan and Mahan
1979 NDDG (National Diabetes Data Group)
1997 American Diabetes Association’s Fourth International Workshop-Conference on Gestational Diabetes Mellitus.
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Etiologicclassification
of
diabetesmellitus
IV- Gestational diabetes mellitus.
Screening
American Diabetes Association’s (1997) fourth international workshop-conference on gestational diabetes recommendations
Screen all pregnant women( 24-28 weeks of gestation )
Excluding:Low risk group:
< 25 years of ageNormal body weight- ve family history- ve H/O abn. glucose metabolismH/O poor obstetric outcomeEthnic group of low diabetes risk
Including:High risk group:
Marked obesityH/O GDMGlycosuriaStrong FH
Including:Average risk group:
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Etiologicclassification
of
diabetesmellitus
IV- Gestational diabetes mellitus.
Screening
American Diabetes Association’s (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 TestGCT
( 50 gm oral glucose load )Glucose after 1hr
Oral Glucose Tolerance Test
OGTT75 or 100
FBS, 1hr, & 2hrs
Glucose Challenge TestGCT
( 50 gm oral glucose load )Glucose after 1hr
Oral Glucose Tolerance Test
OGTT75 or 100
FBS, 1hr, & 2hrs
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Etiologicclassification
of
diabetesmellitus
IV- Gestational diabetes mellitus.
Screening
American Diabetes Association’s (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 TestOGTT
75 or 100FBS, 1hr, & 2hrs
Oral Glucose Tolerance TestOGTT
75 or 100FBS, 1hr, & 2hrs
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Etiologicclassification
of
diabetesmellitus
IV- Gestational diabetes mellitus.
Diagnostic criteria
mg/dl mmol/lFasting 95 5.31-h 180 10.02-h 155 8.63-h 140 7.8
mg/dl mmol/lFasting 95 5.31-h 180 10.02-h 155 8.6
100-g Glucose load
75-g Glucose load
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Etiologicclassification
of
diabetesmellitus
Impaired glucose tolerance IGTImpaired fasting glucose IFG
IGT WHO criteria IGF FPG = 110 - 126 mg/dL
6.1 - 7.0 mmol/L
Normal DiabeticIGTIGF
Why
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Etiologicclassification
of
diabetesmellitus
Impaired glucose tolerance IGTImpaired fasting glucose IFG
Prevalence of Retinopathy by DecilesNHANES III
0
5
1 0
1 5
FPG 90 93 96 98 101 104 109 1202h PG 86 94 102 112 120 133 154 195HbA1c 5.1 5.2 5.4 5.5 5.6 5.7 5.9 6.2
Diabetes Care 1997;20, 1183-1197
Re
tin
opa
thy
%Prevalence of Retinopathy by Deciles
Pima Indians
0
5
1 0
1 5
FPG 93 97 100 105 109 11 6 136 2262h PG 106 11 6 126 138 156 185 244 364HbA1c 5.0 5.2 5.3 5.5 5.7 6.0 6.7 9.5
Diabetes Care 1997;20, 11 83-11 97
Retin
op
ath
y %
Prevalence of Retinopathy by DecilesEgyptians
0
5
1 0
1 5
FPG 84 89 93 99 108 130 178 2582h PG 90 99 110 125 155 218 304 386HbA1c 4.9 5.1 5.4 5.6 6.0 6.9 8.5 10.3
Diabetes Care 1997;20, 1183-1197
Re
tin
opa
thy
%
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Etiologicclassification
of
diabetesmellitus
Impaired glucose tolerance IGTImpaired 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 resistanceHyperinsulinemiaObesityDyslipidemia ( high triglyceride and/or low HDL )
Hypertension
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Etiologicclassification
of
diabetesmellitus
Diagnostic criteria for diabetes mellitusThe new criteria
1
2
3
Fasting plasma glucose ( FPG ) at least 8hours fast
= or > 126 mg/dL ( 7.0 mmol/L )
Two hours plasma glucose (2PG ) after 75 anhydrous glucose in water
= or > 200 mg/dL ( 11.1 mmol/L )
Symptoms of diabetes ( polyuria, polydepsia, and weight loss )
+Random Blood Sugar ( RBS )
casual plasma glucose
= or > 200 mg/dL ( 11.1 mmol/L )
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Etiologicclassification
of
diabetesmellitus
Impaired fasting glucose IFG
For epidemiological studies FPG is:standardization
FacilitationCheep
Diagnosis New criteria WHO criteria
mg/dL mmol/L mg/dL mmol/L
Normal <110 <6.1 < 140 < 7.8
IFG / IGT 110 - <126 6.1- < 7.0 140 - < 200 7.8 - <11.1
? DM = or > 126 = or > 7.0 = or > 200 = or > 11.1
8 hours over night fast. 2 hours post 75 gm glucose load.
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Etiologicclassification
of
diabetesmellitus
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%
Data from NHANES III for individuals 40-74 years old.
The new criteria will lead to 14% ( slightly ) lower estimates of diabetes prevalence.
- 1.99
14%
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Etiologicclassification
of
diabetesmellitus
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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Etiologicclassification
of
diabetesmellitus
HbA1c
Not recommended for diagnosis of diabetes,but valuable for glycemic control of diabetes.
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Etiologicclassification
of
diabetesmellitus
Criteria for testing asymptomatic individuals
• All individual above 45 years of age every 3 years
• Any individual with:
Obese ( > 120% desirable weight or BMI > 27 ).
+ve F/H first degree relatives.
High risk ethnic population.
H/O GDM or big baby ( > 9 lb ).
Hypertension > 140/90
HDL < 35mg/dl ( 0.9 mmol/l ) ±
Triglyceride > 250mg/dl ( 2.82 mmol/l )
Known to have IGT or IFG