1、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, d
2、ysfunction, 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 +
3、 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-FPG7mmol/L -2-h PG7.8mmol/L and 11.1mmol/LIFG-FPG6.1mmol/L and 7.0mmol/L,Laboratory Findings,Urinary glucose Urinary ketone Blood glucose (FPG and 2-hPG) HbA1c and FA(fructosamin
4、e) OGTT Insulin / CP releasing test,Classification (1),Type 1 diabetes -cell destruction, usually leading to absolute deficiencyImmune-mediated diabetesIdiopathic diabetes Type 2 diabetes Ranging from predominantly insulin resistance with relative insulin deficiency to predominantly an insulin secre
5、tory defect with insulin resistance,Classification (2),Other specific types of diabetesDue 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 dia
6、betes mellitus(1),I.Type 1diabetes ( -cell destruction, usually leading to absolute insulin deficiency )A. immune mediatedB. Idiopathic II.Type 2diabetes ( may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance ) I
7、II.Other specific typesA. genetic defects of -cell function1. Chromosome 12, HNF-1 (MODY3)2. Chromosome 7, glucokinase (MODY2)3. Chromosome 20, HNF-4 (MODY1)4. Mitochondrial DNA5. OthersB. Genetic defects in insulin action 1. Type A insulin resistance2. Leprechaunism3. Rabson- Mendenhall syndrome4.
8、Lipoatrophic disease5. Others C. Diseases of the exocrine pancreas1. Pancreatitis2. Trauma / pancreatectomy3. Neoplasia4. Cystic fibrosis5. Hemochromatosis 6. Fibrocalculous pancreatopathy7. Others,Etiologic classification of diabetes mellitus(2),D. Endocrinopathies1. Acromegaly2. Cushings syndrome3
9、. Glucagonoma4. Pheochromocytoma5. Hyperthyroidism6. Somatostatinoma7. Aldosteronoma8. OthersE. Drud- or chemical-induced1. Vacor2. Pentamidine3. Nicotinic acid4. Glucocorticoid5. Thyroid hormone6. Diazoxide7. -adrenergic agonists 8. Thiazides9. Dilantin10. -Interferon11. OthersF. Infections1. Conge
10、nital rubella2. Cytomegalovirus3. Others,Etiologic classification of diabetes mellitus(3),G. Uncommon forms of immune- mediated diabetes1. “Stiff-man” syndrome2. Anti-insulin receptor antibodies3. OthersH. Other genetic syndromes sometimes associated with diabetes1. Downs syndrome2. Klinefelters syn
11、drome3. Turners syndrome4. Wolframs syndrome5. Friedreichs ataxia6. Huntingtons chorea7. Laurence-moon-Biedl syndrome8. Myotonic dystrophy9. Porphyria10. Prader-Willi syndrome11. OthersIV. Gestational diabetes mellitus ( GDM ),Patients with any form of diabetes may require insulin treatment at some
12、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,Gener
13、ally 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 growthretardation,Insulin Resistance ge
14、nes,Obesity genes,Insulin Resistance + Intraabdominal obesity,IGT,T2DM,Western lifestyle,Glucose toxicity,Metabolic Insulin Resistance (FFA),0,80,40,20,60,Year,Disorder of glycemia: etiological types clinical stages,Stages,Types,Normoglycemia Hyperglycemia,Diabetes mellitus,Type 1Type 2Other specifi
15、c typesGestational 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 ketoacidosisNonketotic hyperosmolar syndrome,Microvascular complications,Retinopathy Nephropat
16、hy 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,
17、poor,control,RISK,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 Tre
18、atment,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
19、,Targets for control,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 illn
20、ess 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
21、 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 ev
22、ery 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 Big
23、uanides -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.Thiazolidin
24、ediones,Rosiglitazone Pioglitazone Ciglitazone,5.Glinides,Nategliniderepaglinide,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
25、 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,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,
