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
Polyuria
Polydipsia (thirst)
Weight loss
Weakness
Polyphagia
Blurred vision
Recurrent infection
Impairment 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,Idiopathic
II.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 DM
Generally <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-celldefect
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
IFG Not 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
?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 Treatment
Relief of hyperglycemic symptoms
Correction of hyperglycemia,ketonuria
and hyperlipidemia
Establishment and maintenance of a
desirable body weight,and in children
normal growth and development
Avoidance of acute metabolic disturbance
Prevent or delay the onset of the long-term
complications
Targets for control
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(%) < 6.2 <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 weight
control
Failure
Add biguanide,TZD or ?-glucosidase
inhibitors
Failure
Failure
Combine two of these or add
sulphonylurea or glinide
Add insulin or change to insulin
Check
adherance
at each step
Management Algorithm for
Non-Obese T2DM
D i e t
E x e r ci se
a n d we i g h t
co n tr o l
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 insulin
Check
adherance at
each step
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
Polyuria
Polydipsia (thirst)
Weight loss
Weakness
Polyphagia
Blurred vision
Recurrent infection
Impairment 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,Idiopathic
II.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 DM
Generally <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-celldefect
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
IFG Not 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
?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 Treatment
Relief of hyperglycemic symptoms
Correction of hyperglycemia,ketonuria
and hyperlipidemia
Establishment and maintenance of a
desirable body weight,and in children
normal growth and development
Avoidance of acute metabolic disturbance
Prevent or delay the onset of the long-term
complications
Targets for control
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(%) < 6.2 <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 weight
control
Failure
Add biguanide,TZD or ?-glucosidase
inhibitors
Failure
Failure
Combine two of these or add
sulphonylurea or glinide
Add insulin or change to insulin
Check
adherance
at each step
Management Algorithm for
Non-Obese T2DM
D i e t
E x e r ci se
a n d we i g h t
co n tr o l
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 insulin
Check
adherance at
each step
