Diabetes Mellitus

Zhao-xiaojuan

Introduction

Diabetes mellitus

is a heterogeneous group of

metabolic diseases characterized by

hyperglycemia resulting from defects

in insulin secretion, insulin action, or

both.

Introduction

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.

Symptoms

PolyuriaPolydipsia (thirst)Weight lossWeaknessPolyphagiaBlurred visionRecurrent infectionImpairment of growth

Criteria for diagnosis of diabetes (WHO1999)

Symptoms of diabetes +

Casual plasma glucose ≥ 1.1mmol/l(200mg/dl)

Or

FPG ≥ 7.0mmol/l (126mg/dl)Or

2-hPG ≥ 11.1mmol/l

Diagnostic Criteria WHO1999

IGT

-FPG<7mmol/L

-2-h PG≥7.8mmol/L and <11.1mmol/L

IFG

-FPG≥6.1mmol/L and <7.0mmol/L

Laboratory Findings

Urinary glucose

Urinary ketone

Blood glucose (FPG and 2-hPG)

HbA1c and FA(fructosamine)

OGTT

Insulin / CP releasing test

Classification (1)

Type 1 diabetes β-cell destruction, usually leading to

absolute deficiency Immune-mediated diabetes Idiopathic diabetes

Type 2 diabetes Ranging from predominantly insulin

resistance with relative insulin deficiency to predominantly an insulin secretory defect with insulin resistance

Classification (2)

Other specific types of diabetes Due to other causes, e.g.,genetic defects

in insulin action, diseases of the exocrine pancreas, drug or chemical induced

Gestational diabetes mellitus(GDM) diagnosed during pregnancy

Etiologic classification of diabetes mellitus(1)I.Type 1diabetes ( -cell destruction, usually leading to absolute insulin deficiency ) A. immune mediated B. IdiopathicII.Type 2diabetes ( may range from predominantly insulin resistance with relative insulin

deficiency to a predominantly secretory defect with insulin resistance )III.Other specific types A. genetic defects of -cell function 1. Chromosome 12, HNF-1 (MODY3) 2. Chromosome 7, glucokinase (MODY2) 3. Chromosome 20, HNF-4 (MODY1) 4. Mitochondrial DNA 5. Others B. Genetic defects in insulin action 1. Type A insulin resistance 2. Leprechaunism 3. Rabson- Mendenhall syndrome 4. Lipoatrophic disease 5. Others C. Diseases of the exocrine pancreas 1. Pancreatitis 2. Trauma / pancreatectomy 3. Neoplasia 4. Cystic fibrosis 5. Hemochromatosis 6. Fibrocalculous pancreatopathy 7. Others

Etiologic classification of diabetes mellitus(2) D. Endocrinopathies 1. Acromegaly 2. Cushing’s syndrome 3. Glucagonoma 4. Pheochromocytoma 5. Hyperthyroidism 6. Somatostatinoma 7. Aldosteronoma 8. Others E. Drud- or chemical-induced 1. Vacor 2. Pentamidine 3. Nicotinic acid 4. Glucocorticoid 5. Thyroid hormone 6. Diazoxide 7. -adrenergic agonists 8. Thiazides 9. Dilantin 10. -Interferon 11. Others F. Infections 1. Congenital rubella 2. Cytomegalovirus 3. Others

Etiologic classification of diabetes mellitus(3) G. Uncommon forms of immune- mediated diabetes

1. “Stiff-man” syndrome

2. Anti-insulin receptor antibodies

3. Others

H. Other genetic syndromes sometimes associated with diabetes

1. Down’s syndrome

2. Klinefelter’s syndrome

3. Turner’s syndrome

4. Wolfram’s syndrome

5. Friedreich’s ataxia

6. Huntington’s chorea

7. Laurence-moon-Biedl syndrome

8. Myotonic dystrophy

9. Porphyria

10. Prader-Willi syndrome

11. Others

IV. Gestational diabetes mellitus ( GDM )

Patients with any form of diabetes may require insulin treatment at some stage of their disease. Such use of insulin dose not, of itself, classify the patient.

Type 1 DMGenerally <30 years

Rapid onset

Moderate to severe symptoms

Significant weight loss

Lean

Ketonuria or keto-acidosis

Low fasting or post-prandial C-peptide

Immune markers(anti-GAD,ICA,IA-2)

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

Pathophysiological model for development of obesity and T2DM

Beta-cell defect

Intra-uterin growth

retardation

InsulinResistance

genes

Obesity genes

InsulinResistance

+Intraabdominal

obesity

IGT T2DM

Westernlifestyle

Glucosetoxicity

MetabolicInsulin

Resistance(FFA)

0 804020 60

Year

Disorder of glycemia: etiological types clinical stages

Stages

Types

Normoglycemia Hyperglycemia Diabetes mellitus

Type 1

Type 2

Other specific types

Gestational diabetes

Normal glucose tolerance

IGT and/or

IFGNot insulin requiring

Insulin requiring for control

Insulin requiring for survival

Acute,life-threatening consequences

Hyperglycemia with ketoacidosis

Nonketotic hyperosmolar syndrome

Microvascular complications

Retinopathy

Nephropathy

Peripheral neuropathy

Autonomic neuropathy

Macrovascular complications

Atherosclerotic cardiovascular disease

Peripheral vascular disease

cerebrovascular disease

Others

Hypertension

Abnormalities of lipoprotein metabolism

Periodontal disease

Potential chronic complications of elevated HbA1c

good poorcontrol

RIS

K

•Microalbuminuria•Mild Retinopathy•Mild Neuropathy

•Albuminuria•Macular Edema•Proliferative Retinopathy•Peridontal Disease•Impotence•Gastroparesis•Depression

•Foot Ulcers•Angina•Heart Attack•Coronary Bypass•Surgery•Stroke•Blindness•Amputation•Dialysis•Kidney Transplant

The Aims of TreatmentRelief of hyperglycemic symptomsCorrection of hyperglycemia, ketonuria and hyperlipidemiaEstablishment and maintenance of a desirable body weight, and in children normal growth and developmentAvoidance of acute metabolic disturbancePrevent or delay the onset of the long-term complications

Targets for controlOptim

al 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(%) < 6.2 <6.2-8.0 >8.0

Blood pressure (mmHg)

<130/80 >130/80-<160/95

>160/95

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) <2.5 2.5-4.4 >4.4

Management

Essentials of management

Monitoring of glucose levels

Food planning

Physical activity

Treatment of hyperglycemia

2.Monitoring of Glucose Levels

Blood glucose levels

- before each meal

- at bedtime

Urine glucose testing

Urine ketone tests (should be performed during illness or when blood glucose is 20mmol/L )

3.Food Planning

Weight control.

50-60%of the total dietary energy should come from complex carbohydrates.

20-25% form fats and oils.

15-20% from protein.

Restrict alcohol intake.

Restrict salt intake to below 7g/d.

4.Physical Activity

Physical activity play an important role in the management of diabetes particularly in T2DM. Physical activity improves insulin sensitivity, thus improving glycemic control, and may help with weight reduction

Do sparingly avoid sedentary activities

Do regularly participate in leisure activities and recreational sports

Do every day adopt healthy lifestyle habits

5.Drug Treatment

If the patient is very symptomatic or has

a very high blood glucose level, diet and

lifestyle changes are unlikely to achieve

target values. In this instance,

pharmacological therapy should be

started without delay.

Treatment

Sulphonylureas

Biguanides

-Glucosidase inhibitors

Thiazolidinediones

Glinides

Insulin

Combination therapy

1.Sulphonylureas

Chlorpropamide

Tolbutamide

Glibenclamide

Glipizide

Gliclazide

Gliguidone

Glimepiride

2.Biguanides

Metformin

Phenformin

Buformin

3.-Glucosidase inhibitors

Acarbose

Voglibose

Miglitol

4.Thiazolidinediones

Rosiglitazone

Pioglitazone

Ciglitazone

5.Glinides

Nateglinide

repaglinide

6.Insulin

Insulin is the most efficacious

pharmacologic treatment for patients with

diabetes

6.Insulin

Indication

Preparation

Therapy

Adverse reaction

Management Algorithm for Overweight and Obese T2DM

Diet Exercise and weightcontrol

Failure Add biguanide, TZD or -glucosidase inhibitors

Failure

Failure

Combine two of these or add sulphonylurea or glinide

Add insulin or change to insulinCheck adherance at each step

Management Algorithm for Non-Obese T2DM

DietExerciseand weightcontrol

Failure

Failure

Failure

Add sulphonylurea, biguanide, -glucosidase inhibitors or glinide

Combine sulphonylurea or glinide with biguande and/or -glucosidase inhibitors and/or add TZD

Add insulin or change to insulinCheck adherance at each step