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Diabetes Mellitus

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Title: Diabetes Mellitus


1
Diabetes Mellitus
  • Zhao-xiaojuan

2
Introduction
  • Diabetes mellitus
  • is a heterogeneous group of metabolic
    diseases characterized by hyperglycemia resulting
    from defects in insulin secretion, insulin
    action, or both.

3
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.

4
Symptoms
  • Polyuria
  • Polydipsia (thirst)
  • Weight loss
  • Weakness
  • Polyphagia
  • Blurred vision
  • Recurrent infection
  • Impairment of growth

5
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

6
Diagnostic Criteria WHO1999
  • IGT
  • -FPGlt7mmol/L
  • -2-h PG7.8mmol/L and lt11.1mmol/L
  • IFG
  • -FPG6.1mmol/L and lt7.0mmol/L

7
Laboratory Findings
  • Urinary glucose
  • Urinary ketone
  • Blood glucose (FPG and 2-hPG)
  • HbA1c and FA(fructosamine)
  • OGTT
  • Insulin / CP releasing test

8
Classification (1)
  • Type 1 diabetes
  • ß-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

9
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

10
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

11
Etiologic classification of diabetes mellitus(2)
  • D. Endocrinopathies
  • 1. Acromegaly
  • 2. Cushings 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

12
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. Downs syndrome
  • 2. Klinefelters syndrome
  • 3. Turners syndrome
  • 4. Wolframs syndrome
  • 5. Friedreichs ataxia
  • 6. Huntingtons 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.
13
Type 1 DM
  • Generally lt30 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)

14
Type 2 DM
  • Generally gt40 years
  • Slowly onset
  • Not severe symptoms
  • Obese
  • Ketoacidosis seldom occur
  • Nonketotic hyperosmolar syndrome
  • Normal or elevated C-peptide levels
  • Genetic predisposition

15
Pathophysiological model for development of
obesity and T2DM
Beta-cell defect
Glucose toxicity
Intra-uterin growth retardation
Insulin Resistance Intraabdominal obesity
IGT
T2DM
Insulin Resistance genes
Metabolic Insulin Resistance (FFA)
Western lifestyle
Obesity genes
Year
0
80
40
20
60
16
Disorder of glycemia etiological types clinical
stages
Normoglycemia Hyperglycemia
Stages
Diabetes mellitus
Normal glucose tolerance
IGT and/or IFG
Not insulin requiring
Insulin requiring for control
Insulin requiring for survival
Types
Type 1 Type 2 Other specific types Gestational
diabetes
17
Acute,life-threatening consequences
  • Hyperglycemia with ketoacidosis
  • Nonketotic hyperosmolar syndrome

18
Microvascular complications
  • Retinopathy
  • Nephropathy
  • Peripheral neuropathy
  • Autonomic neuropathy

19
Macrovascular complications
  • Atherosclerotic cardiovascular disease
  • Peripheral vascular disease
  • cerebrovascular disease

20
Others
  • Hypertension
  • Abnormalities of lipoprotein metabolism
  • Periodontal disease

21
Potential chronic complications of elevated HbA1c
  • Foot Ulcers
  • Angina
  • Heart Attack
  • Coronary Bypass
  • Surgery
  • Stroke
  • Blindness
  • Amputation
  • Dialysis
  • Kidney Transplant
  • Albuminuria
  • Macular Edema
  • Proliferative Retinopathy
  • Peridontal Disease
  • Impotence
  • Gastroparesis
  • Depression

RISK
  • Microalbuminuria
  • Mild Retinopathy
  • Mild Neuropathy

good
poor
control
22
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

23
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 gt7.0 gt10.0
HbA1c() lt 6.2 lt6.2-8.0 gt8.0
Blood pressure (mmHg) lt130/80 gt130/80-lt160/95 gt160/95
BMI (kg/m2) Male female lt25 lt24 lt27 lt26 ?27 ?26
Total cholesterol(mmol/L) lt4.5 ?4.5 ?6.0
HDL- cholesterol(mmol/L) gt1.1 1.1-0.9 lt0.9
Triglycerides(mmol/L) lt1.5 lt2.2 ?2.2
LDL- cholesterol(mmol/L) lt2.5 2.5-4.4 gt4.4
24
Management
  • Essentials of management
  • Monitoring of glucose levels
  • Food planning
  • Physical activity
  • Treatment of hyperglycemia

25
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 )

26
3.Food Planning
  • Weight control.
  • 50-60of 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.

27
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

28
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.

29
Treatment
  • Sulphonylureas
  • Biguanides
  • ?-Glucosidase inhibitors
  • Thiazolidinediones
  • Glinides
  • Insulin
  • Combination therapy

30
1.Sulphonylureas
  • Chlorpropamide
  • Tolbutamide
  • Glibenclamide
  • Glipizide
  • Gliclazide
  • Gliguidone
  • Glimepiride

31
2.Biguanides
  • Metformin
  • Phenformin
  • Buformin

32
3.?-Glucosidase inhibitors
  • Acarbose
  • Voglibose
  • Miglitol

33
4.Thiazolidinediones
  • Rosiglitazone
  • Pioglitazone
  • Ciglitazone

34
5.Glinides
  • Nateglinide
  • repaglinide

35
6.Insulin
  • Insulin is the most efficacious pharmacologic
    treatment for patients with diabetes

36
6.Insulin
  • Indication
  • Preparation
  • Therapy
  • Adverse reaction

37
Management Algorithm for Overweight and Obese T2DM
Diet Exercise and weight control
Failure
Add biguanide, TZD or ?-glucosidase inhibitors
Failure
Combine two of these or add sulphonylurea or
glinide
Failure
Check adherance at each step
Add insulin or change to insulin
38
Management Algorithm for Non-Obese T2DM
Failure
Add sulphonylurea, biguanide, ?-glucosidase
inhibitors or glinide
Failure
Combine sulphonylurea or glinide with biguande
and/or ?-glucosidase inhibitors and/or add TZD
Failure
Check adherance at each step
Add insulin or change to insulin
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