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.


Agenda


2.Definition & C/P.



Agenda


2.Definition & C/P.


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


Agenda


2.Definition & C/P.


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).

Type 2 Diabetes


Aswan Feb. 2016

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

Pathophysiology of Type2 Diabetes

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

Natural History f Type 2 Diabetes

Pathophysiology of Type2 Diabetes

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

Type1 Diabetes


Aswan Feb. 2016

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

Pathogenesis of type 1 diabetes

Gestational Diabetes


Aswan Feb. 2016

Gestational Diabetes Care In Upper Egypt

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

Pathophysiology of GDM

Insulin Resistance

Relative Insulin Deficiency

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

Diabetes in Pregnancy

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


≥153 mg/dL (8.5 mmol/L2 ≥155 mg/dL (8.6 mmol/L)2


≥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

Lastly we hope that course will achieve

its goals and help you all in getting the

best of the forthcoming conference

UEDA Board


Aswan Feb. 2016

Ueda 2016 2-pathophysiology ,classification & diagnosis of diabetes - khaled el hadidy

Health & Medicine