Ueda 2016 2-pathophysiology ,classification & diagnosis of diabetes - khaled el hadidy
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Transcript of Ueda 2016 2-pathophysiology ,classification & diagnosis of diabetes - khaled el hadidy
Pathophysiology, Screening,Diagnosis & Classification Of Diabetes
UEDA Diabetes Mini-Course
Aswan Feb. 2016
DR. Khaled El Sayed El Hadidy. MDProfessor of Internal Medicine
Head of Internal Medicine DepartmentHead of Diabetes and Endocrinology Unit
Beni - Suef University.UEDA ( IDF member )
Classification, Pathophysiology & Diagnosis of Diabetes “1”
Agenda
1.Normal physiology.
2.Definition & C/P.
3.Clinical classes of Diabetes Mellitus.
Classification, Pathophysiology & Diagnosis of Diabetes “1”
Agenda
1.Normal physiology.
2.Definition & C/P.
3.Clinical classes of Diabetes Mellitus.
Classification, Pathophysiology & Diagnosis of Diabetes “1”
Agenda
1.Normal physiology.
2.Definition & C/P.
3.Clinical classes of Diabetes Mellitus.
Definition of diabetes
Chronic hyperglycemia associated with long term damage to ….
Eyes
Kidneys
Nerves
Heart and blood vessels
Gums•
Signs and symptoms of hyperglycaemia
Polydipsia
Polyuria
Nocturia
Visual disturbance
Fatigue
Weight loss
Infections
Hunger
Classification, Pathophysiology & Diagnosis of Diabetes “1”
Agenda
1.Normal physiology.
2.Definition & C/P.
3.Clinical classes of Diabetes Mellitus.
Clinical classes of diabetes:
1. Type 1 diabetes – results from B cell destruction due to an autoimmune process usually leading to insulin deficiency.
2. Type 2 diabetes – results from a progressive insulin secretorydefect on the background of insulin resistance.
3. Gestational diabetes mellitus (GDM) – any degree of glucose intolerance with onset or first recognition during pregnancy.
4. Other specific types of diabetes – due to other causes such as genetic defects in Beta cell function, genetic defects in insulin action, diseases of the exocrine pancreas (e.g. cystic fibrosis), and drug- or chemical-induced causes (e.g. in the treatment of HIV/AIDS or after organ transplantation).
Pancreatic islet dysfunction (T2DM)
↑ Glucose
Fewer-cells
-cellsHypertrophy
InsufficientInsulin
ExcessiveGlucagon
–+
↓ Glucose Uptake
↑ HGO
+
HGO=hepatic glucose output.Adapted from Ohneda A, et al. J Clin Endocrinol Metab. 1978; 46: 504–510; Gomis R, et al. Diabetes Res Clin Pract. 1989; 6: 191–198.
Pathogenesis of Type 2 Diabetes
Hyperglycemia
Liver
Increased GlucoseProduction
Reprinted with permission from DeFronzo RA. Diabetes. 1988;37:667-687. Copyright © 1998 American Diabetes Association. All rights reserved.
Impaired Insulin Secretion
Pancreas
Liver
Decreased Glucose Uptake
Muscle
Muller WA, et al. N Engl J Med. 1970;283:109-115.
80
100
120
140
160
–60 0 60 120 180 240Time (min)
Glu
cago
n (p
g/m
L)
0
50
100
150
–60 0 60 120 180 240
Insu
lin
(μU
/mL)
NGTT2DM
Insulin Glucagon
Islet dysfunction: Inappropriate Insulin and Glucagon Responses to
Glucose in Patients With T2DM
NGTT2DM
Incretins
Intestine Secretion Insulin = Incretin Incretins are insulinotropic substances
released by the GIT.
Incretins account for approximately 20%–60% of insulin secretion after a meal in normal individuals.
~90% incretin activity is due to:
Glucagon-Like Peptide-1 (GLP-1)
Glucose-dependent insulinotropicpolypeptide (GIP).
L L L
GLP-1 GLP-1 GLP-1
InsulinGlucagon
Slowed gastric
emptying
Early
Satiety
Inactive
GLP-1
DPP-4
enzyme
GLP-1
Incretin Effect in Subjects without and with Type 2 Diabetes Given Glucose by IV and Orally
Time, min
IR In
sulin
, mU
/L nm
ol/L
0.6
0.5
0.4
0.3
0.2
0.1
0
80
60
40
20
0
18060 1200
Control Subjects (n=8)
Patients with Type 2 Diabetes (n=14)
Time, min
IR I
ns
uli
n,
mU
/L
nm
ol/ L
0.6
0.5
0.4
0.3
0.2
0.1
0
80
60
40
20
0
18060 1200
Oral glucose load Intravenous (IV) glucose infusion
Incretin Effect
Nauck M et al., Diabetologia 1986; 29:46–52
Increased
HGP
IncreasedGlucagonsecretion
Decreased insulinsecretion
Decreasedglucoseuptake
HYPERGLYCEMIA
Neurotransmitterdysfunction
Islet α-cell
Decreased incretineffect
Increasedlipolysis
Increasedglucose
reabsorption
A New Paradigm for the Pathophysiology and Treatment of Type 2 Diabetes Mellitus Ominous Octet
De Fronzo RA. Diabetes 2009;58:773–95
HGP = hepatic glucose production
SCREENING & DIAGNOSIS
SD1 Each health service should decide whether to have
a program to detect people with undiagnosed
diabetes.
Universal screening for undiagnosed diabetes is
not recommended.
SD2 Detection programs are usually based on a two-step
approach:
Step 1 Identify high-risk individuals using a risk
assessment questionnaire.
Step 2 Glycemic measure in high-risk individuals.
Individuals Considered To Be At High Risk Of Type 2 Diabetes
People with IGT or IFG
All patients with a history of a cardiovascular event (acute myocardial infarction, angina, peripheral vascular disease or stroke)
People aged 35y and over originating from the Pacific Islands, Indian subcontinent or China
People aged 40y and over with body mass index (BMI) ≥30 kg/m2 or hypertension
Women with a history of GDM
Women with polycystic ovary syndrome (PCOS) who are obese
Patients on antipsychotic medication
Non-modifiable Risk Factors For Type 2 Diabetes
Age > 40 years
Family history or genetic predisposition
Ethnicity
History of IGT, IFG
Vascular disease
History of gestational diabetes or delivery of macrosomic baby
PCO
Schizophrenia
Hypertension
Dyslipidaemia
Modifiable Risk Factors For Type 2 Diabetes
Abdominal or central obesity
Overweight
Physical inactivity
Dietary factors
FPG 100–125 mg/dL(5.6–6.9 mmol/L): IFG
OR
2-h plasma glucose 140–199 mg/dL (7.8–11.0 mmol/L): IGT
OR
A1C 5.7–6.4%
Prediabetes*
* For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately
greater at higher ends of the range.
American Diabetes Association Standards of Medical Care in Diabetes. Classification and diagnosis of diabetes. Diabetes Care 2016; 39 (Suppl. 1): S13-S22
SD4 Where a random plasma glucose level ≥ 100mg/dl and < 200 mg/dl is detected, a FPG shouldbe measured or an HbA1c measured.
SD5 Use of HbA1c as a diagnostic test for diabetesrequires that stringent quality assurance tests arein place and assays are standardized to criteriaaligned to the international reference values, andthere are no conditions present which precludeits accurate measurement.
SD6 People with screen-detected diabetes should beoffered treatment and care.
SCREENING & DIAGNOSIS
Impaired glucose tolerance Impaired fasting glucose
Intermediate states
High risk of developing diabetes
Increased risk of cardiovascular disease
Prevention strategies must be implemented to prevent or delay progression
Metabolic syndrome
Cluster of risk factors or syndrome
Found in 70 - 80% of people with T2DM
Diagnostic criteria varies globally
Associated with three-fold increase in heart disease and stroke
Associated with two-fold increase in major cardiovascular events
(International Diabetes Federation, 2006)
Revised ATP III Metabolic Syndrome Oct 2005
*Diagnosis is established when 3 of these risk factors are present.†Abdominal obesity is more highly correlated with metabolic risk
factors than is BMI. ‡Some men develop metabolic risk factors when circumference is only
marginally increased.
<40 mg/dL<50 mg/dL or Rx for ↓ HDL
MenWomen
>102 cm (>40 in)>88 cm (>35 in)
MenWomen
100 mg/dL or Rx for ↑ glucoseFasting glucose
130/85 mm Hg or on HTN Rx
Blood pressure
HDL-C
150 mg/dL or Rx for ↑ TGTG
Abdominal obesity†
(Waist circumference‡)
Defining LevelRisk Factor
Pathogenesis of type 1 diabetes
Immunological activationProgressive beta-cell destruction Insufficient beta-cell functionGenetic susceptibility Immune factors
Other autoimmune diseaseAntigen-specific antibodies
Environmental triggerVirusesBovine serum albuminNitrosamines: cured meatsChemicals: vacor (rat poison), streptozotin
Gestational Diabetes
One of the most challenging aspects of diabetes practice
Seemingly easy: Practically difficult
Needs a lot of commitment on part of doctor, patient and family
Success can be achieved if we try together
Definition
Glucose intolerance with onset or first recognition during pregnancy
Characterized by β-cell function that is unable to meet the body’s insulin needs
Buchanan, Wiang, Kjos, Watanabe 2007
Risk factors for GDM
High risk
Obesity
Age >25ys
Diabetes in 1st degree relative
Previous history of GDM or glucose intolerance
Previous infant with macrosomia> 3.5 kg
High risk ethnic group; South Asian, East Asian, Indigenous American or Australian, Hispanic
PCOS
Low risk
Age less than 25 years
No previous poor pregnancy outcomes
No diabetes in 1st degree relatives
Normal prepregnancyweight and weight gain during pregnancy
No history of abnormal glucose tolerance
Perkins, Dunn, Jagastia, 2007
Why diagnose and treat GDM?
No increase in congenital anomalies Short term risks for the baby
MacrosomiaNeonatal hypoglycemia JaundicePreterm birthBirth injuryHypocalcemia/ hypomagnesimiaRespiratory distress syndrome
Long term risks for the babyObesityType 2 diabetes
GDM Diagnosis
2 Approaches for Diagnosing Gestational Diabetes Mellitus (GDM)
AACE- and ADA-recommended
1-step 75-g 2-hour oral glucose tolerance test (OGTT) 1,2
or
ACOG- recommended 2 steps: a 50-g 1-hour glucose challenge test (GCT) ≥140 mg/dL , followed by a 100-g 3-hour OGTT (if necessary)3
GDM Diagnostic Criteria for OGTT Testing
75-g 2-hour† 100-g 3-hour*
Fasting plasma glucose (FPG)
≥92 mg/dL (5.1 mmol/L)2 ≥95 mg/dL (5.3 mmol/L)2
1-hour post-challenge glucose
≥180 mg/dL (10.0 mmol/L)2 ≥180 mg/dL (10.0 mmol/L)2
2-hour post-challenge glucose
≥153 mg/dL (8.5 mmol/L2 ≥155 mg/dL (8.6 mmol/L)2
3-hour post-challenge glucose
≥140 mg/dL (7.8 mmol/L)2
†A positive diagnosis requires that test results satisfy any one of these criteria*A positive diagnosis requires that ≥2 thresholds are met or exceeded
.1AACE. Endocr Pract. 2011;17(2):1-53.
.2ADA. Diabetes Care. 2013;36(suppl 1):11-66.
.3Committee on Obstetric Practice. ACOG. 2011;504:1-3.
Recommendations:Detection and Diagnosis of GDM (1)
Screen for undiagnosed type 2 diabetesat the first prenatal visit in those withrisk factors, using standard diagnostic criteria
Screen for GDM at 24–28 weeks of gestation in pregnant women not previously known to have diabetes
Screen women with GDM for persistent diabetes at 6–12 weeks postpartum, using OGTT, nonpregnancy diagnostic criteria
ADA. III. Detection and Diagnosis of GDM. Diabetes Care 2014;37(suppl 1):S18