pathophysiology ,classification & diagnosis of diabetes - khaled el hadidy

1. Pathophysiology, Screening,
Diagnosis & Classification Of Diabetes
UEDA Diabetes Mini-Course
Aswan Feb. 2016
DR. Khaled El Sayed El Hadidy. MD
Professor of Internal Medicine
Head of Internal Medicine Department
Head of Diabetes and Endocrinology Unit
Beni - Suef University.
UEDA ( IDF member )

2. Classification, Pathophysiology &
Diagnosis of Diabetes “1”
Agenda
1.Normal physiology.
2.Definition & C/P.
3.Clinical classes of Diabetes Mellitus.

3. Classification, Pathophysiology &
Diagnosis of Diabetes “1”
Agenda
1.Normal physiology.
2.Definition & C/P.
3.Clinical classes of Diabetes Mellitus.

7. Classification, Pathophysiology &
Diagnosis of Diabetes “1”
Agenda
1.Normal physiology.
2.Definition & C/P.
3.Clinical classes of Diabetes Mellitus.

8. Definition of diabetes
Chronic hyperglycemia associated with
long term damage to ….
 Eyes
 Kidneys
 Nerves
 Heart and blood vessels
 Gums
•

9. Signs and symptoms of hyperglycaemia
 Polydipsia
 Polyuria
 Nocturia
 Visual disturbance
 Fatigue
 Weight loss
 Infections
 Hunger

10. Classification, Pathophysiology &
Diagnosis of Diabetes “1”
Agenda
1.Normal physiology.
2.Definition & C/P.
3.Clinical classes of Diabetes Mellitus.

11. 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 secretory
defect 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).

12. Type 2 Diabetes
UEDA Diabetes Mini-Course
Aswan Feb. 2016

13. Pancreatic islet dysfunction (T2DM)
↑ Glucose
Fewer
-cells
-cells
Hypertrophy
Insufficient
Insulin
Excessive
Glucagon
–+
↓ 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.

14. Pathogenesis of Type 2 Diabetes
Hyperglycemia
Liver
Increased Glucose
Production
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

15. Pathophysiology of Type2 Diabetes

17. Muller WA, et al. N Engl J Med. 1970;283:109-115.
80
100
120
140
160
–60 0 60 120 180 240
Time (min)
Glucagon(pg/mL)
0
50
100
150
–60 0 60 120 180 240
Insulin(μU/mL)
NGT
T2DM
Insulin Glucagon
Islet dysfunction:
Inappropriate Insulin and Glucagon Responses to
Glucose in Patients With T2DM
NGT
T2DM

18. Natural History f Type 2 Diabetes

19. Pathophysiology of Type2 Diabetes

20. 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 insulinotropic
polypeptide (GIP).

21. L L L
GLP-1 GLP-1 GLP-1
InsulinGlucagon
Slowed gastric
emptying
Early
Satiety
Inactive
GLP-1
DPP-4
enzyme
GLP-1

22. Incretin Effect in Subjects without and with
Type 2 Diabetes Given Glucose by IV and Orally
Time, min
IRInsulin,mU/L
nmol/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
IRInsulin,mU/L
nmol/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

23. Increased
HGP
Increased
Glucagon
secretion
Decreased insulin
secretion
Decreased
glucose
uptake
HYPERGLYCEMIA
Neurotransmitter
dysfunction
Islet α-cell
Decreased incretin
effect
Increased
lipolysis
Increased
glucose
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

24. 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.

25. 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

26. 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

27. Modifiable Risk Factors
For Type 2 Diabetes
Abdominal or central obesity
Overweight
Physical inactivity
Dietary factors

28. 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

30. SD4 Where a random plasma glucose level ≥ 100
mg/dl and < 200 mg/dl is detected, a FPG should
be measured or an HbA1c measured.
SD5 Use of HbA1c as a diagnostic test for diabetes
requires that stringent quality assurance tests are
in place and assays are standardized to criteria
aligned to the international reference values, and
there are no conditions present which preclude
its accurate measurement.
SD6 People with screen-detected diabetes should be
offered treatment and care.
SCREENING & DIAGNOSIS

31. 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

32. 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)

33. 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
Men
Women
>102 cm (>40 in)
>88 cm (>35 in)
Men
Women
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

34. Type1 Diabetes
UEDA Diabetes Mini-Course
Aswan Feb. 2016

35. Pathogenesis of type 1 diabetes
Immunological activation
Progressive beta-cell destruction
Insufficient beta-cell function
Genetic susceptibility
Immune factors
Other autoimmune disease
Antigen-specific antibodies
Environmental trigger
Viruses
Bovine serum albumin
Nitrosamines: cured meats
Chemicals: vacor (rat poison), streptozotin

36. Pathogenesis of type 1 diabetes

37. Gestational Diabetes
UEDA Diabetes Mini-Course
Aswan Feb. 2016

38. Gestational Diabetes Care
In Upper Egypt

39. 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

40. 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

41. Pathophysiology of GDM
Insulin Resistance
Relative Insulin Deficiency

42. 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 prepregnancy
weight and weight gain
during pregnancy
 No history of abnormal
glucose tolerance
Perkins, Dunn, Jagastia, 2007

43. Diabetes in Pregnancy

44. Why diagnose and treat GDM?
 No increase in congenital anomalies
 Short term risks for the baby
Macrosomia
Neonatal hypoglycemia
Jaundice
Preterm birth
Birth injury
Hypocalcemia/ hypomagnesimia
Respiratory distress syndrome
 Long term risks for the baby
Obesity
Type 2 diabetes

45. 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.

46. Recommendations:
Detection and Diagnosis of GDM (1)
 Screen for undiagnosed type 2 diabetes
at the first prenatal visit in those with
risk 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

47. Lastly we hope that course will achieve
its goals and help you all in getting the
best of the forthcoming conference
UEDA Board
UEDA Diabetes Mini-Course
Aswan Feb. 2016