Diabetes MellitusDiabetes Mellitus

Zhao XiaoJuanZhao XiaoJuan

Department of EndocrinologyDepartment of Endocrinology

The First Hospital of China Medical UniversityThe First Hospital of China Medical University

2007.10.232007.10.23

Adapted from Zimmet P et al. Diabet Med. 2003;20:693-702.

25.039.759%

25.039.759%

10.419.788%

10.419.788%

38.244.216%

38.244.216%

1.11.7

59%

1.11.7

59%

13.626.998%

13.626.998%

81.8 156.191%

81.8 156.191%

18.2 35.997%

18.2 35.997%

Prevalence of Diabetes MellitusPrevalence of Diabetes Mellitus

million

2007 ： 246 000 000 2025 ： 380 000 000

2003 ： 189 000 000 2025 ： 324 000 000 72%

OutlineOutline

1. Definition

2. Diagnosis

3. Classification

4. Complications

5. Management

1.Definition1.Definition

Diabetes mellitus is characterized by chronic hyperglycemia with disturbances of carbohydrate, fat, and protein metabolism resulting from defects in insulin secretion, insulin action, or both.

1.Definition1.Definition

The chronic hyperglycemia of

diabetes is associated with long-

term damage, dysfunction, and

failure of various organs, especially

the eyes, kidneys, nerves, heart, and

blood vessels.

American Diabetes Association, 2003

OutlineOutline

1. Definition

2. Diagnosis

3. Classification

4. Complications

5. Management

2. Diagnosis2. Diagnosis

Diagnostic Criteria (WHO 1999)

Symptoms of diabetes + Casual plasma glucose

11.1mmol/L （ 200mg/dl) or

Fasting plasma glucose （ FPG ） 7.0mmol/L （ 126mg/dl ） or

2h-Post load plasma glucose(2h-PG)

11.1mmol/L （ 200mg/dl ） If positive, confirm diagnosis with 7days

SymptomsSymptoms

thirst

polyuria

polyphagia

unexplained weight loss

weakness (fatigue)

Criteria for the diagnosis of DMCriteria for the diagnosis of DM

mmol/L (mg/dl)mmol/L (mg/dl) NormalNormal

Impaired Impaired

Fasting Fasting

Glucose (IFG)Glucose (IFG)

Impaired Impaired

Glucose Glucose

Tolerance Tolerance

(IGT)(IGT)

Diabetes Diabetes

MellitusMellitus

(DM)(DM)

Fasting plasma Fasting plasma

glucose (glucose (FPG)FPG) 6.1 6.1 and

7.0

--

7.0

2-Hour postload 2-Hour postload

glucose (glucose (2-hPG)2-hPG) 7.8 -- 7.8 and

11.1

11.1

Random Random plasma plasma

glucoseglucose-- -- 11.1 with

symptoms

Laboratory FindingsLaboratory Findings

1. Blood glucose (FPG and 2-hPG)

2. Urinary glucose

3. Urinary ketone

4. HbA1c and FA (fructosamine)

5. OGTT

6. Insulin / CP releasing test

7. Others (Blood lipid/ UAER/ Immune markers (anti-GAD,ICA,IAA)

FPG 8-12 mmol/LFPG 12–15 mmol/L

FPG < 8 mmol/L

FPG > 18 mmol/L

normal

T2DM

0.40

1.00

0.80

0.60

insulin

0.20

0

–30 0 30 60 90 120 150 180 210 240

time (min)

nmol/L

Insulin releasing testInsulin releasing test

OutlineOutline

1. Definition

2. Diagnosis

3. Classification

4. Complications

5. Management

3. Classification 3. Classification (1999WHO)(1999WHO)

Type1 diabetes (T1DM)Type1 diabetes (T1DM) Immune mediated

Idiopathic

Type 2 diabetes (T2DM)Type 2 diabetes (T2DM) Other specific typesOther specific types Genetic defects of -cell function

Genetic defects of insulin action Disease of the exocrine pancreas Endocrinopathies Drug - or chemical-induced Infections Anti-insulin receptor antibodies Other genetic syndromes sometimes associated with diabetes

Gestational diabetes mellitus (GDM)Gestational diabetes mellitus (GDM)

3.1 Type 1 diabetes3.1 Type 1 diabetes

β-cell destruction, usually leading to

absolute deficiency

1. Immune-mediated diabetes (Type1A)

Latent autoimmune diabetes in adults, LADA

2. Idiopathic diabetes (Type1B)

AutoantibodiesAutoantibodiesislet cell autoantibody (ICA)

autoantibody to insulin (IAA)

autoantibody to glutamic acid decarboxylase (GADA)

autoantibody to tyrosine phosphatases(IA-2 / IA-2)

Which reflects the autoimmune processes that

have led to -cell destruction

Type 1 DMType 1 DM

Generally <25 years

Rapid onset

Moderate to severe symptoms

Significant weight loss or lean

Ketonuria or keto-acidosis

Low fasting or post-prandial C-peptide

Immune markers (ICA,GADA, IA-2)

3.2 Type 2 diabetes3.2 Type 2 diabetes

Heterogeneous diseases

The most common form of diabetes

Disorders of insulin action and

insulin secretion

Specific etiology is not known

IR – a reduced response of target IR – a reduced response of target tissues to circulating insulintissues to circulating insulin

Glucose

Defective insulin secretion

Excessive fatty acid release

Reduced glucoseuptake

Excessive glucose

production

Carbohydrate

Resistance to the action of insulin

Insulin

3.2.2 3.2.2 -cell dysfunction-cell dysfunction

Reduced ability of -cells to secrete

insulin

Impaired ability of -cells to

compensate for IR

Genetic and environmental

pathophysiology

Features of Type 2 DMFeatures of Type 2 DM

Generally ＞ 40 years

Slowly onset

Not severe symptoms

Obese

Ketoacidosis seldom occur

Nonketotic hyperosmolar syndrome

Normal or elevated C-peptide levels

Genetic predisposition

3.3 3.3 Other specific types of diabetesOther specific types of diabetes

Due to other causes, e.g: Due to other causes, e.g:

genetic defects of -cell function (MODY)

genetic defects of insulin action

disease of the exocrine pancreas

endocrinopathies

drug or chemical induced

others

3.4 3.4 Gestational diabetes mellitus (GDM)Gestational diabetes mellitus (GDM)

GDM is defined as any degree of glucose intolerance with onset or first recognition during pregnancy

6 weeks or more after delivery the woman should be reclassified

Course of diseaseCourse of disease

1. Normal glucose tolerance (NGT)

2. Impaired glucose homeostasis (IGH)

3. Diabetes mellitus (DM)

Impaired fasting glucose (IFG)

Impaired glucose tolerance (IGT)

Clinical stages Clinical stages

NormoglycemiaNormoglycemia

Normal glucose

tolerance

HyperglycemiaHyperglycemia

Impaired Impaired glucose glucose

regulationregulation

IGT / IFGIGT / IFG

Diabetes mellitusDiabetes mellitus

Not insulin Not insulin requiringrequiring

Insulin requiring Insulin requiring for controlfor control

Insulin requiring Insulin requiring for survivalfor survival

StagesStages

TypesTypes

Type 1Type 1

Type 2Type 2

Other Other Specific Specific TypesTypes

GDMGDM

Diabetes MellitusDiabetes Mellitus

Zhao XiaoJuanZhao XiaoJuan

Department of EndocrinologyDepartment of Endocrinology

The First Hospital of China Medical UniversityThe First Hospital of China Medical University

2007.11.12007.11.1

OutlineOutline

1. Definition

2. Diagnosis

3. Classification

4. Complications

5. Management

4. Chronic Complications4. Chronic Complications

Diabeticretinopathy

Diabeticnephropathy

Cardiovasculardisease

Stroke

Diabeticneuropathy

Peripheral vascular disease

Diabetic foot

macrovascularmacrovascularmicrovascularmicrovascular

DM: Impact on patientDM: Impact on patient

Blindness 10%

Loss of reading vision 15%

Amputation 12%

End stage kidney failure 30%

Myocardial infarction 2-4

Excess mortality 2-8

OthersOthers

Hypertension

Abnormalities of lipoprotein metabolism

Periodontal disease

Metabolic syndromeMetabolic syndrome

Abdominal obesity

IGR or DM

Hypertension

Increased triglycerides

Decreased HDL cholesterol

Microalbuminuria

Acute Acute ComplicationsComplications

Acute, life-threatening consequences:

Hyperglycemia with ketoacidosis

Nonketotic hyperosmolar syndrome

ComplicationsComplications

complications

MacrovasculaMacrovascularr

MicrovasculaMicrovascularr

acute chronic Infection

DKA

NHDC CerebrovascularCerebrovascular

CardiovascularCardiovascular

Peripheral VascularPeripheral Vascular

NephropathyNephropathy

RetinopathyRetinopathy

NeuropathyNeuropathy

Diagnosis procedureDiagnosis proceduresymptoms clues &risk factors

FPG / 2h-PG

equivocal raised valuesunder criteria

except DMOGTT NGTNGT

IFG/IGTIFG/IGT

DMDM

classifications

complicationcomplicationss

OutlineOutline

1. Definition

2. Diagnosis

3. Classification

4. Complications

5. Management

5. Management5. Management

1. Education

2. Food planning

3. Physical activity

4. Pharmacological treatment

5. Monitoring

5. 1Education of DM5. 1Education of DM

It is important that all diabetics are educated in self regulation:

The nature of the disorder

Risk of complications.

Individual targets of treatment

food intake, physical activity and drugs

Self-monitoring of blood or urine glucose

How to cope with emergencies such as

hypoglycemia

5.2 5.2 MonitoringMonitoring

Blood glucose levels

- before each meal

- at bedtime

Urine glucose testing

Urine ketone tests (should be performed during illness or when

blood glucose is 11.1mmol/L )

5.3 Food Planning5.3 Food Planning

Weight control

50-60%of the total dietary energy should

come from complex carbohydrates

20-25% from fats and oils

15-20% from protein

Restrict alcohol intake

Restrict salt intake to below 7g/d

5.45.4 Physical ActivityPhysical Activity

Physical activity play an important role

Help weight reductionHelp weight reduction

Improving insulin sensitivityImproving insulin sensitivity

Improving glyceamic controlImproving glyceamic control

5.45.4 Physical ActivityPhysical Activity

Do sparingly: avoid sedentary activities

Do regularly: participate in leisure activities and recreational sports

Do every day: adopt healthy lifestyle habits

5.5 pharmacological therapy 5.5 pharmacological therapy

5.5.1 Insulin5.5.1 Insulin

Indication

Preparation

Therapy

Adverse reaction

5.5.1.1 Indications of insulin5.5.1.1 Indications of insulin

T1DM&GDM

T2DM

Acute metabolic disturbance :NHDC /DKA

Pregnancy and lactation

surgery

Severe diabetics

5.5.1.2 Insulin Preparations5.5.1.2 Insulin PreparationsPreparationsPreparations

HumanHuman AnaloguesAnalogues AnimalAnimal

Ultra-shortUltra-short Lispro Lispro

aspartaspart

ShortShort Novolin RNovolin R

Humulin RHumulin R

R IR I

semilentesemilente

IntermediateIntermediate Novolin NNovolin N

Humulin NHumulin N

NPHNPH

LenteLente

LongLong Novolin ULNovolin UL

Humulin ULHumulin UL

PZIPZI

UltralenteUltralente

Ultra-longUltra-long GlargineGlargine

DetemirDetemir

MixtureMixture Novolin 30RNovolin 30R

Novolin 50RNovolin 50R

Humulin 70/30Humulin 70/30

Time actions of various types of insulinTime actions of various types of insulin

Type Onset of action

Peak effect

Duration of action

Ultra short-acting 1

Short-acting 0.5 2-4 6-8

Intermediate-acting 2-4 8-12 18-24

Long-acting 5-7 16-18 30-36

Ultra long-acting 1-2 - 24

Insulin mixtures Variable actions

page 981 table 7-24-9

Rapid Acting Insulin AnaloguesRapid Acting Insulin Analogues

Insulin Aspart

-Asp(B28)-Insulin

Insulin Lispro

-Lys(B28),Pro(B29)-Insulin

Long Acting Insulin AnaloguesLong Acting Insulin Analogues

Insulin Glargine

-Glycine(A21)+2 arginine(B30)

Insulin Detemir

5.5.1.3 Insulin Therapy5.5.1.3 Insulin Therapy

Breakfas Lunch Dinner Sleep

1 RI RI RI

2 RI+/-NPH +/- RI RI+/- NPH

3 RI RI RI NPH

4 RI+UL RI RI

5 RI+UL RI RI+UL

6 RI RI RI UL

4:004:00 16:0016:00 20:00 20:00 24:0024:00 4:004:00

BreakfastBreakfast LunchLunch DinnerDinner

Ideal Basal/Bolus Insulin Absorption PatternIdeal Basal/Bolus Insulin Absorption Pattern

8:008:0012:0012:008:008:00

TimeTime

Pla

sma

Insu

lin

Pla

sma

Insu

lin

Aspart Aspart – adding an additional injection– adding an additional injection

Continuous Subcutaneous Insulin Infusion Continuous Subcutaneous Insulin Infusion ( CSII)( CSII)

5.5.1.4 5.5.1.4 Problems associated with insulinProblems associated with insulin

Hypoglycemia reaction

Insulin resistance

Somogyi phenomenon

Osmotic lens change (visual

blurring)

Insulin edema

5.5.2 5.5.2 Oral anti-diabetic (OAD) agentsOral anti-diabetic (OAD) agents

1. Sulphonylureas

2. Biguanides

3. -Glucosidase inhibitors

4. Thiazolidinediones

5. Glinides

6. Other

5.5.2.1 SU5.5.2.1 SU

insulin secretagogueinsulin secretagogue

Main action is the stimulation of insulin

secretion from the pancreatic -cells

The first-line drug in type 2 diabetes

patients who are not very obese

Main adverse reaction is hypoglycemia

5.5.2.2Biguanides5.5.2.2Biguanides

insulin sensitizerinsulin sensitizer

Increases insulin sensitivity

Reduced hepatic glucose production

First-line therapy in the obese

Without weight gain and hypoglycemia.

Adverse reactions are gastrointestinal intolerance and lactic acidosis

5.5.2.3 5.5.2.3 -Glucosidase inhibitors-Glucosidase inhibitors

Decrease post-prandial hyperglycemia

Have weight-reducing effect.

First-line therapy with diet, or in

combination with SU, biguanides and

insulin.

Do not cause hypoglycemia

5.5.2.4 5.5.2.4 Thiazolidinediones (TZD)Thiazolidinediones (TZD)

Reduce insulin resistance

Do not enhance insulin production.

Do not cause hypoglycemia.

Conjunction with other antiglycemic agents

5.5.2.5 Glinides5.5.2.5 Glinides

A new generation of SU-like agents

Stimulate first-phase insulin

secretion

May be used as monotherapy

Combination with biguanides or

thiazolidinediones

5.5.2.6 Others5.5.2.6 Others

Lipaglutide (GLP-1 Analogues)

Drug Treatment inDrug Treatment in Type 2 Diabetes Type 2 DiabetesPancreas

LiverMuscle

Impaired insulin secretion

Reduced muscleglucose uptake

TZDMetformin

TZDMetformin

SulphonylureaGlinidesGlinides

Increased hepaticglucose production

Glucosidase inhibitors Metformin

Hyperglycemia

_

stomach intestin

e

Combination therapyCombination therapy

small doses of each drug

avoid the individual side-effects of

each agent

Combination therapy in T2DMCombination therapy in T2DM

SulphonylureasSulphonylureasGlinidesGlinides

-Glucosidase Glucosidase inhibitorsinhibitors

BiguanidesBiguanidesThiazolidinedionesThiazolidinediones

insulin

OAD + basal insulin OAD + multiple daily

insulin injections

OAD monotherapy

OAD combinations OADs

uptitration

7

6

9

8

10

Duration of diabetes

A1C = 7%

OAD = oral anti-diabetic

A1C = 6.5%

Adapted from Del Prato S, et al. Int J Clin Pract 2005; 59:1345-55.

A1C

(%

)Treatment to Target: Aggressive Management of Glycemic Control

ADA 2007

intensive insuln

+ SU

+TZD

+ basal insuln

intensive insuln or basal insuln metformin

TZD*

healthy lifestyle + metformin

+ basalinsuln

+ SU

+ TZD

HbA1C > 7%

HbA1C > 7%

HbA1C > 7%

lifesty

le +

metfo

rmin

+ basal insuln

Diabetes Care 2007 ； 30 （ SUPPLEMENT 1）

The Aims of TreatmentThe Aims of Treatment

Relief of hyperglycemic symptoms

Avoidance of acute metabolic disturbance

Prevent or delay the onset of the long-term complications

In children normal growth and development

Optimal

Fair Poor

Plasma glucose

(mmol/L)

FPG

2-hPG

4.4-6.1

4.4-8.0

7.0

10.0

>7.0

>10.0

HbA1c(%) < 6.5 <6. 5-7.5 >7.5

Blood pressure (mmHg) <130/80 >130/80-

<140/90

>140/90

BMI (kg/m2) Male

female

<25

<24

<27

<26

27

26

Total cholesterol(mmol/L) <4.5 4.5 6.0

HDL- cholesterol(mmol/L) >1.1 1.1-0.9 <0.9

Triglycerides(mmol/L) <1.5 <2.2 2.2

LDL- cholesterol(mmol/L) <3.0 2.5-4.0 >4.0

Targets for control

Number of persons

< 50005000–74,00075,000–349,000350,000–1,499,0001,500,000–4,999,000> 5,000,000No data available

Total cases > 370 million adults

WHO. Available at: www.who.int/diabetes/facts/world_figures/en/. Last accessed: January 2005.

Worldwide prevalence of diabetes in 2030 (projected)

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