Download
slide1 n.
Skip this Video
Loading SlideShow in 5 Seconds..
DIABETES MELLITUS PowerPoint Presentation
Download Presentation
DIABETES MELLITUS

DIABETES MELLITUS

436 Views Download Presentation
Download Presentation

DIABETES MELLITUS

- - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

  1. DIABETES MELLITUS PROF. SIRAJ A. MIRA PROFESSOR/CONSULTANT KING ABDULAZIZ UNIVERSITY HOSPITAL JEDDAH

  2. DIABETES MELLITUS • DIABETES MELLITUS AND ITS COMPLICATIONS ARE NOW THE THIRD LEADING CAUSE OF MORTALITY IN THE UNITED STATES AND THE SECOND LEADING CAUSE OF BLINDNESS.

  3. -ESTIMATED PREVALENCE IN U.S.A 3 - 6 % AND INCREASING RAPIDLY -ESTIMATED PRVALENCE IN SAUDI ARABIA to 2003 18-24%

  4. STROKE, M1 AND END – STAGE RENAL • DISEASE ARE FREQUENT CAUSES OF • MORTALITY. • THE DISEASE IS FOUND THROUGHOUT THE WORLD AT VARYING PRVALENCE RATE. • - IN PIMA INDIANDS PREVALENEC RATE AT 50 %

  5. NIDDM IS MAJOR CAUSE OF MORBIDITY AND MORTALITY PREVAILING FROM,MACROVASCULAR DISEASE , BUT ALSO FROM SPECIFIC COMPLICATIONS OF DISABETES , RETINOPATHY , NEPHROPATHY AND NEUROPATHY.

  6. DIABETES MELLITUS DIABETES MELLITUS IS ADISEASE COMPLEX CHARACTERISED BY RELATIVE OR ABSOLUTE INSUFFICIENCY OF INSULIN SECRETION AND A CONCMMITANT INTENSITIVITY OR RESISTANCE TO THE METABOLIC ACTION INSULIN TARGET TISSUE.

  7. NON INSULIN DEPENDENT DABETES ( NIDDM ) IS by FAR THE MOST PREVALENT FORM OF DIABETES WORLD – WIDE , FORMING MORE THAN 95 % OF ALL DIABETES IN MANY DEVELOPING COUNTRIES .

  8. RISK FACTORS FOR IDDM • Genetic Factors HLA class 2 antigens in DR + DQ regions = >90% Caucasian patients have either DR3 or DR4 , DR2 is protective. • Environmental Factors: No Specific factors have been identified

  9. ( cont . ) • Viruses • The risk greater for children born between February-September • IgM antibodies against conxsackievirus found in 25-30% of new cases suggesting recent infection

  10. Coxsackievirus B RNA has been detected in 65% of children under the age of 7 years with newly diagnosed IDDM compared with 4% of controls which is consistent with recent Infection..

  11. (CONT) • Dietary Factors • Cow,s mild feeding fist 4 months indicated risk of subsequent IDDM, whilst breast feeting appeared protective. • Case controlled studies in Sweden have indicated a positive association between IDDM ,high protein intake and frequency of consumption of foods containing nitrosamine.

  12. (CONT) • Loss of first- phase insulin secretion in response to intravenous glucose is highly Predictive of early onset of diabetes.

  13. PATHOGENESIS OF IDDM • Islet cell antibodies in ICA are present in 80% of children at the time of diagnosis and have been detected up to 15 years before diagnosis of IDDM. • Long- term follow up has shown that family members with ICA are at greatly increased risk of progression to diabetes and this risk is directly related to persistence and strength of the ICA reaction.

  14. ( cont.) • Other antibodies include: • insulin autoantibodies ( IAA) • antibodies to GAD ( Glutamate decarboxylase ) • Protein tyrosine phosphatase IA-2 • The presence of ICA together with 2 or more markers indicate a greater than 80% risk of progressing for insulin treatment in otherwise healthy family members .

  15. NATURAL HISTORY OF BETA-CELL DEFECT GENETIC PREDISPOSITION IMMUNOLOGIC ABNORMALITES NORMAL INSUILN RELEASE PROGRESSIVE IMPAIRMENT IN INSULIN RELEASE 100 OVERT DIABETES BETA-CELL MASS (% OF MAX) “HONEYMOON” PERIOD 50 BIRTH 0 0 TIME(YR)

  16. HONEYMOON PHASE DUE TO BETA-CELL RESERVE INSULIN REQUIREMENT DECREASED LASTS FOR UP TO 1 YR PATIENT ALWAYS RELAPSES TREATMENT PROPOSED TO EXTEND HONEYMOON PERIOD STILL EXPERIMENTAL

  17. EVIDENCE FOR AUTOIMMUNE DISEASE RELATIONSHIPS OF TYPE I WITH OTHER AUTOIMMUNE DISEASES ASSOCIATION BETWEEN HLA GENES AND DIABETES PRESENCE OFANTI-ISULET AND/OR ANTI-INSULIN ANTIBIES PRESENCE OF INFLAMMATORY CELLS AROUND ISLETS EVIDENCE OF IMMUNE SYSTEM ACTIVATION

  18. The spectrum of autoimmune diabetes Acute B cell failure Insulitis 1AA/1A-2 antibodies/1CA/GAD antibodies HLA associations +++ Slow B cell failure Less insulitis GAD antibodies/ ICA HLA associations+ 0 50 Years

  19. Clinical spectrum ? LADA Slow type 1 Classic type 1 Type 1 in infancy 0 50 Years

  20. The clinical and immunogenetic characteristics of insulin dependent diabetes mellitus change according to age at presentation 1AA,insulin auto-antibodies:1A-2,protein1A-2:GAD,glutamate decarboxylase;ICA,islet cell antibodies,LADA, latent autoimmune diabetes in the adult

  21. DR2 TYPE I DR3 DR4 A 2 ---------- BW51--------------- DR4 B8-------------B15 GENERALLY LOW IN POPULATION

  22. CLASSIFICATION • W.H.O. CLASSIFICATION • TYPE I ( INSULIN DEPENDET DIABETES MLLITUS IDDM) • HAVE LITTLE OR NO ENDOGENOUS INSULIN • ONSET OF DISEASE IS CLNICALLYABRUPT WITH : MARKED POLYURIA, POLYDIPSIA POLYPHAGIA WEIGHT LOSS, FATIGUE. • THESE PATIENTS ARE HIGHLY PRONE TO KETOSTS • THEY FREQUENT ARE PRESNT IN AND INITIAL ATTACK OF KETOACIDOSIS

  23. CLASSIFICATION TYPE I CONTD . . • GENERALLY HAVE WEIGHT LOSS AND ARE FREQUENTLY AT OR BELOW IDEAL WEIGHT AND ARE THEREFORE PARTICULARY SENSITIVE TO INSULIN (ESPECIALLY REGULAR OR SOLUBLE INSULIN). • CAN OCCUR AT ANY AGE , BUT PEAKS IN THE • MIDDLE OF THE FIST DECADE AND AGAIN AT THE • TIME OF GROWTH ACCELERATION OF ADOLESCENCE. • OLD TERM – JUVENILE ONSET DIABETES MLLITUS .

  24. CLASSIFICATION TYPE I CONTD… • A PRODOMAL PHAE OF POLYUREA , POLYDYPSIA AND WEIGH LOSS MAY PRECEDE THE DEVELOPMENT OF KETOACIDOSIS BY A PERIOD OF MONTHS ( MOST COMMONLY 2 - 4 WEEKS ). • GENETIC PREDISPOSISTION ( FAMILY HISTORY LESS STRONGLY ASSOCIATED THAN WITH TYPE II ). • ASSOCIATED WITH SOME HLA HITOCMPATIBILTY ANTIGENS EG . B8, B15, DW3, DW4.

  25. CLASSIFICATION TYPE I CONTD .. . • ASSOCIATED WITH ISLET CELL ANTIBODIES • VIRUS AETIOLOGY IS IMPLICATED ESPECIALLY COXACKIE B4 AND MUMPS. • SIGNIFICANT ASSOCIATION WITH CERTAIN AUTOIMMUNE DISORDERS - ADDISON ‘ S , HASHIMOTO’S TYROIDITS, HYPOPARATHYROIDISM, PERNICIOUS ANAEMIA

  26. CLINICAL PRESENTATION OF TYPE I DIABETES

  27. % 100 90 80 70 60 50 40 30 20 10 DKA 25% COMA 5% WEIGHT LOSS 35% POLYURIA 75%

  28. LABORATORY PRESENTATION OF TYPE I DIABETES

  29. % 100 90 80 70 60 50 40 30 20 10 HCO3<18 60% PH< 7.2 20% HYPERGLYCEMIA AND/ OR GLYCOSURIA 100% KETONURIA 85%

  30. NIDDM IS ALMOSTCERTAINLY A HETEOGENOUS MIXTURE OF CONDITIONS CHARACTERISEDBY HYPERGLYCAEMIA , OF INSULIN RESISTANCE AND INSULIN HYOP-SECRETION AND LACK OF DEPENDENCE ON EXOGENOUS INSULIN TO MAINTAIN LIFE

  31. TYPE II ( NIDDM ) FOR MAJOR ABNORMLITIES APPEAR TO ACCOUNT FOR THE INAPPROPRIATE HYPERGLYCMIA SEEM IN TYPE II ( NIDDM) PATIENTS 1- DESCREASE IN QUANTITY INSULIN SECRETED 2- DELAY IN THE TIME OF RELEASE OF INSULIN 3- IMPAIRMET OF THE EFFCTS OF INSULIN ON THE PEREPHERAL TISSUES ( INSULIN RESISTANCE ) 4- INCREASE IN HEPATIC GLUCOSE PRODUCTION

  32. CLASSIFICATION DIABETES MELLITUS TYPE I ( IDDM ) TYPE II ( NIDDM) - OBESE - NONBESE GESTATIONAL DIABETES OTHER TYPES IMPAIRED GLUCOSE TOLERANCE ( IGT)

  33. MODY • Due primarily to a Beta cell defect resulting in inadequate insulin secretion for a given blood glucose level . • There is no significant increase in insulin resistance. • Various mutations in the giucokinase gene on chromosomes 7p, probably account for 10-50% of cases of MODY . • Giucokinase – Mody is characterized by early onset ( often less than 18 months of age ) mild hyperglycaemia which is usually controIIed by diet alone until old age.

  34. MODY • Autosmal Dominant • Diagnostic Criteria • Diagnosis before 25 years of age in atleast 2 family member . • No requirement of insulin treatment 5 years after diagnosis and/or C- Peptide positivity. • Convincing vertical transmission of type II Diabetes mellitus through at least three generations. • Accounts upto 1% of Diabetes Mellitus population.

  35. Table 2. the different subtypes of maturity-onest diabetes of the young (MODY)

  36. MODY

  37. AETIOGICAL FACTOR IN NIDDM GENETICS : ( STRONG FAMILY AGGREGATES ALMOST 100% CONCORDANCE RATE IN IDENTICAL TWINS ( PYKE ET AL ) RACE : ( DIABETES IN MIGRANT INDIANS)

  38. OBSITY : (PIMA INDIANS NAURANS) PHYSICAL INACTIVITY LONGIVITY : (DIABETES PREVALENCE INCREASES WITH AGE E .G . PREVALENCE RATE > 30 % IN ELDERLY IN FINLAND)

  39. GENES AND NIDDM • Two genes have been implicated so far : NIDDM 1 and NIDDM2 • MODY (Autosomal Dominant ) • -MODY 1, (HNF-4) extremely uncommon) • -MODY 2, (Glucokinase gene-impairs B-cell glucose • sensing) • MODY 3, ( Hepatocyte Nuclear factor 1- ( HNF-1) are more common • Maternally inherited diabetes with deafness ( MIDD) Late onset IDDM

  40. Table 22.5

  41. Genetic syndromes associated with an early onset NIDDM

  42. CLASSIFICATION • TYPE II CONTD . . . • THE CLINICALPRESENTATION VARIES GREATLY: I . THEY MAY MANIFEST DM AFTER THE DEVELOPMENT OF COMPLICTIONS ( E .G.RE TIOPATHY ) . II . MAY HAVE SIGNIFICANT POLYRIA , POLYDIPSIA ,EASY FATIGUABILITY ETC . III . MAY BE FOUND BY CHANCE ON ROUTINE examination

  43. CLASSIFICATION TYPE II CONTD. . . • MILDTO AMRKED OBES IS PRESENT IN 80% TYPE II AT THE TIME OF DIAGNOSIS . • OBESITY IS A MAJOR RISK FACTOR RROBABLY DUE TO THE DECREASE INSULIN RECEPTOR DENSITY AND ABNORMAL COUPLING OF RECEPTOR TO METABOLIC PROCESS THAT OCCUR IN THE OBESE STATE

  44. MOSTPATIENTS ARE DIAGNOSED AFTER • THE AGE OF 40 YEARS • OLD NAME - MANTURIY ONSET D.M .

  45. A GTT IS DOME FOR THOSE IN THE IMPAIRED TOLERANCE RANGE COMMON CAUSES OF TRANSIENT CARBOHYDRTE INTOLERANCES : PHYSICAL OR EMOTIONAL STRESS INFECTION UNDER NUTRITION BED REST TRAUMA

  46. DIAGNOSTIC CRITERIA FOR DIABETES NONOREGNANT ADULITS

  47. PLASMAOTHER CRITERIA GLUCOSE ( mg/dI) RANDOM > 200CLASSIC SIGNS AND SYMPTOMS OR FASTING >126 ON AT LEST 2 OCCASIONS OR FASTING < 126SUSTAINED ELEVATED LASMA GLUCOSE DURING AT LEAST 2OGTTs

  48. Dx OF IMPAIRED GLUCOSE TOLERANCE IN ADULTS* OGTT SAMPLE PLASMA GLUCOSE VALUES ( mg/dI) FASTING < 126 2 HOUR 126- 199 INTERVENING>200 *NONPREGANT

  49. DLAGNOSTIC CRITERIA WHO