professor and head unit-1 department of endocrinology diabetes … · 2020. 11. 28. · nihal...
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Nihal ThomasMD DNB (Endo) MNAMS FRACP (Endo) FRCP(Edin)Professor and head Unit-1Department of Endocrinology Diabetes and MetabolismChristian Medical College Vellore
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Featuring……… Definition
Diagnosis
Metabolic syndrome concept
Classification
Case scenarios
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Definition
Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both.
Diagnosis and Classification of Diabetes Mellitus American Diabetes Association
Diabetes Care 28: 2005
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Prevalence of retinopathy by deciles of the distribution of FPG, 2hrPPG and HbA1C
National Health And Nutritional Epidemiologic Survey (NHANES III)
The cut‐off level for FPG has been defined, based on the sharp increase in the micro vascular complications when the plasma glucose crosses this level
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Criteria for diagnosis
Fasting > 126 mg% on one
occasion
OR
Postprandial > 200 mg% on one
occasion with symptoms or Check a second
time if with out symptoms
OR
HbA1c >6.5%
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Additions…
Impaired fasting Glycaemia (IFG) 100 - 125 mg%
Impaired Glucose Tolerance (IGT) 140 – 199 mg%
Hba1C 6.0‐6.5%
(ADA criteria)
Fasting Plasma Glucose Oral Glucose Tolerance Test
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Advantages of A1C Testing Compared With FPG or 2HPG for the Diagnosis of Diabetes
Standardized and aligned to the DCCT/UKPDS
Better index of overall glycemic exposure and risk for long-term complications
Substantially less biologic variability
Substantially less pre-analytic instability
No need for fasting or timed samples
Relatively unaffected by acute perturbations in glucose levels
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Disadvantages of A1C Testing Compared With FPG or 2HPG for the Diagnosis of Diabetes
Lack of Accuracy and Standardization of HbA1c in India
Expensive
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What do the terms
Impaired fasting Glycaemia
AND
Impaired glucose tolerance imply?
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It means Increased risk for Cardiovascular
/Cerebrovascular disease
A predictor for subsequent diabetes
mellitus
Diabetic range glucose values
unmasked with stress
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• FPG …………Relative risk of developing DM• >90mg/dl 1.7• >100mg/dl 3.2• >110mg/dl 6.0
Vellore Rural Data Fasting Plasma Glucose checked in 1995
Oral Glucose Tolerance Test done in 2006
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What is the metabolic syndrome ?(Or Syndrome X or Insulin Resistance Syndrome)
It describes a cluster of CVD risk factors and metabolic alterations associated with excess body fat.
Abdominal obesity
Glucose Intolerance / DiabetesHypertensionDyslipidaemia
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ATP III Operational DefinitionOccurrence of any 3 of the following abnormalities:
↑ Fasting Serum TGL >150 mg/dL ↑ Blood pressure (> 130/85 mm Hg) Serum Serum HDL Cholesterol
< 40 mg/dL
< 50mg/dL ↑ waist circumference
> 102 cm
> 88 cm Impaired fasting glucose (>100 mg/dL)
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WHO DefinitionIGT / IFG/T2DM + any of the two below
↑ waist: hip ratio
> 0.9
> 0.85
Elevated Blood Pressure > 140/90 mm Hg Elevated Triglycerides > 150mg/dl Low HDL cholesterol Microalbuminuria
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Prevalence of the Metabolic Syndrome
EGIR % ATPIII % IDF %Women(n=289)
6 7 8
Men(n=279)
13 18 19
IDF
EGIRATPIII
14.7
2.7
22.1
11
11.9
20.2
17.4
IDF
EGIRATPIII
20.9
0
41.8
16.3
14
0
7
WomenMen
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Revised IDF Criteria for the Metabolic syndrome
Criteria for Clinical Diagnosis of the Metabolic Syndrome
Measure Categorical cut points
Elevated waist circumference Population-and country-specific definitions
M<88cm F<80cm
Elevated triglycerides (drug treatment for elevatedtriglycerides is an alternate indicator)
>150 mg/dL
Reduced HDL cholesterol (drug treatment for reducedHDL cholesterol is an alternate indicator)
<40 mg/dL for males and<50 mg/dL for females
Elevated blood pressure (drug treatment for elevatedblood pressure is an alternate indicator)
Systolic >130 mm Hg and/ordiastolic >85 mm Hg
Elevated fasting glucose (drug treatment for elevatedglucose is an alternate indicator)
>100 mg/dL
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BMI vs WHR in relation to CHD risk
Yusuf S et al. Lancet 2005;366:1640-9
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Klein S et al. NEJM 2004;350:2549-2557
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Classification Type 1 Diabetes/LADA
Type 2 Diabetes
Other Specific Types
Gestational Diabetes
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Type 1 Diabetesß‐cell destruction, leading to absolute insulin deficiency
Immune‐mediated diabetes (common) Idiopathic diabetes.
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Type 1 DiabetesInsulitis
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Immune System Innate Immunity Acquired Immunity
NK Cells MacrophagesDendritic CellsGranulocytes
T CellsB Cells
NK T Cells
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Autoimmune destruction
Thymic Education of T Cells
Negative Positive
Autoreactive T Cells maintained by Central Tolerance
T Cell Escape to periphery
Antigen presented to T Cell
T Cell mediated apoptosis
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NK Cells LGL in peripheral blood – role in tumor immune surveillance and viral infection
Main role in Innate immunity Cytolytic activity ‐ by producing cytokines & ADCC Activation markers – CD16, CD 56, CD57, CD94 Inhibitory markers – CD 158a, CD94 Effector function mediated by receptor –ligand interaction
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To elicit an autoimune response ……..
NK cell receptor + Ligands on APC
Killer Cell Ig Receptor HLA
Activated NK cell
Release of Perforins & Granzymes
Apoptic Cell death
Activation of T Cell IFN ‐γ
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Pancreatic β‐cell assault – Is it Innate or acquired ?Exact mechanism of trigger for Pancreatic β‐cell destruction – NOT KNOWN
Genetic susceptibility
Environmental Trigger Beta cell death
HLA Environmental toxinsDietVirus
Autoimmunity( Innate & Adaptive )
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Genes that alter : Immune System
Innate Immunity Acquired Immunity
NK Cells MacrophagesDendritic CellsGranulocytes
T CellsB Cells
NK T Cells
KIR Genes( Killer Cell Ig‐ like Genes )
TLR Genes( Toll like receptor Genes )
VIRAL INFECTION
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Pathogenesis of Type I DMEnvironment ?Viral infe..??
Genetic HLA-DR3/DR4
Severe Insulin deficiency
ß cell Destruction
Type I DM
Autoimmune Insulitis (GAD,ICA IAA)
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LADA(Latent Autoimmune Diabetes of the Adult)
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Type 2 Diabetes
May range from predominantly insulin resistance to predominantly an insulin secretory defect.
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Type 2 Diabetes
Loss of ß cellsAmyloid depositsHyalinization
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Pathogenesis of Type 2 DMEnvironment
Low Birth WeightObesityGenetic
ß cell defectGenetic
ß cell exhaustion Type 2 DM
Insulin resistance
Relative Insulin Def.
May requireInsulin
Secretory Defect
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Physical Activity on the decline…………..
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Physical Activity on the decline…………..
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The economic driving factors……
Adam Drewnowski and SE Specter. Poverty, obesity, and diet costs. Am J Clin Nutr 2004;79:6 –16
> Rs. 70/-per kg
Rs. 90/-per kg
…Consumer Price Index shifts favour unhealthy products
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Mean Body Mass Index (1 Ponderal Index) of subjects by FTO genotypes according to place of birth
* significant difference in mean BMI Z score by FTO types (p<0.05). SD score for the whole cohort is set at 0.
Rural Urban
Mat
erna
l (63
2)
Pate
rnal
(631
)
Birt
h1 (5
93)
Infa
ncy
(427
)
Chi
ldho
od (5
14)
Ado
lesc
ence
(524
)
Adu
lthoo
d (6
30)
Mat
erna
l (14
88)
Pate
rnal
(148
8)
Birt
h1 (1
413)
Infa
ncy
(112
2)
Chi
ldho
od (1
299)
Ado
lesc
ence
(114
0)
Adu
lthoo
d (1
484)
-0.6
-0.4
-0.2
0.0
0.2
0.4
0.6
0.8
Mat
erna
l (21
20)
Pate
rnal
(211
9)
Birt
h1 (2
006)
Infa
ncy
(293
)
Chi
ldho
od (1
549)
Ado
lesc
ence
(181
3)
Adu
lthoo
d (2
114)
AAATTT
*
All
Z sc
ore
*
*
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Other Specific TypesA. Genetic defects in Beta Cell function / Insulin secretion
B. Genetic defects in Insulin Action
C. Diseases of the Exocrine Pancreas
D. Endocrinopathies
E. Drug or Chemical Induced
F. Infections
G. Uncommon Immune forms
H. Genetic Syndromes with Diabetes
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Genetic defects of insulin secretionMaturity Onset Diabetes of the Young (MODY) Six genetic loci on different chromosomes have been identified to date.
Glucokinase related MODY(MODY 2) is common….but in India….HNF‐4 alfa.
Usually Nonketotic /Nonobese Often in sucessive generations
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Genetic defects in insulin action
1. Type A insulin resistance2. Leprechaunism3. Rabson‐Mendenhall syndrome4. Lipoatrophic diabetes5. Others
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Adapted from F Karpe
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Diseases of the pancreas
Acquired causes include Pancreatitis, Trauma,
infection, pancreatectomy, and pancreatic carcinoma.
Fibrocalculous pancreatopathy
Cystic fibrosis and Hemochromatosis
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Fibrocalculous pancreatic diabetes
The classical triad of clinical presentation in tropical chronic pancreatitis:
Abdominal pain.
Maldigestion leading to steatorrhoea.
Diabetes (fibrocalculous pancreatic diabetes).
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Drug induced diabetes
Drugs and hormones can impair insulin sensitivity and reduce insulin action.
glucocorticoids, phenytoin, thiazides & interferons
Intravenous pentamidine can permanently destroy pancreatic ß‐cells.
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Clinical Scenarios
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CASE 1 36 year old Mr.R who had his blood glucose levels checked since he had a family history of diabetes
BMI : 31 kg/m2
His fasting plasma glucose(FPG) was 118 mg%, 2hr PPBG was 155 mg%.
DIAGNOSIS ?
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Case 2 20 year old gentleman was diagnosed to have diabetes on a pre‐employment check up.He was born of non consanguineous marriage and his mother and his maternal grand father were having diabetes
His BMI was 21 kg/m2 . BP =120/80mm Hg.
Probable Type ?
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Case 339 yr old Mr. Al was diagnosed to have diabetes..
Polyuria and weight loss in previous 4 months. No recurrent abdominal pain/steatorrhea
BMI: 20 kg/m2. Urine ketones:negative. Glycemic control for first one year achieved with OHAs.
Required insulin thereafter. GAD antibodies were positive Type of diabetes‐
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Case 4 20 year old lady was diagnosed to have diabetes mellitus.
Menstrual irregularity+ BMI =31 kg/m2
Proximal muscle weakness+, Purplish abdominal striae+
Further work up‐
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Summarizing………. Diabetes Mellitus should be looked at
as a whole with the metabolic syndrome.
Impaired fasting Glycaemia and glucose tolerance should be given due importance
In the young the clinical features should be taken into account to determine the cause of diabetes.
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Thank you