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Recent advance in diabetes mellitus ppt BIOCHEMISTRY

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Recent advance in diabetes mellitus ppt BIOCHEMISTRY

  1. 1. 8/26/2013 1 Dr Vijaya Marakala MD vkunder637@gmail.com
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  3. 3. Gains • Better living conditions • Variety of foods • Better transportation • Better communication Losses • More eating • Less physical activity • More stress 8/26/2013 3
  4. 4. Obesity Diabetes Hypertension and cardiovascular diseases Leading to…. 8/26/2013 4
  5. 5. DIABETES MELLITUS Definition Classification Lab diagnosis Recent aspects 8/26/2013 5
  6. 6. A metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action or both . 8/26/2013 6
  7. 7. 2009(in millions) INDIA 50.8 CHINA 43.2 US 26.8 0 10 20 30 40 50 60 Inmillions Top 3 countries number of adults with diabetes, 2009 8/26/2013 7
  8. 8. One person in the world dying of diabetes every ten seconds. There will be 2 new diabetic cases in the world being identified every 10sec. In the national survey 54.1% of diabetes developed it in the most productive years of their lives IDF predicts that diabetes will cost the world economy at least US$376 billion in 2010, or 11.6% of total world healthcare expenditure.8/26/2013 8
  9. 9. Year Author Place Area Prevalence(%) Urban Rural 1971 Tripathy et al Cuttak Central 1.2 1972 Ahuja et al New Delhi North 2.3 1979 Gupta et al Multicentere 3 1.3 1984 Murthy et al Tenali South 4.7 1986 Patel Bhadran West 3.8 1988 Ramachandran et al Kudremukh South 5 1989 Kodali et al Gangavathi South 2.2 1989 Rao et al Eluru South 1.6 1991 Ahuja et al New Delhi North 6.7 1992 Ramachandran et al Madras South 8.2 2.4 1997 Ramachandran et al Madras South 11.6 2000 Ramakutty et al Kerala South 12.4 2.5 2001 Ramachandran et al National DESI 12.1 2001 Mishra et al New Delhi North 10.3 2001 Mohan et al Chennai South 12.18/26/2013 9
  10. 10. 10 Zimmet, Nature 2001 India: 2000:32 mill 2020: 81 mill 8/26/2013
  11. 11. Classification of DIABETES MELLITUS Type 1 Type 2 Other Gestational 8/26/2013 11
  12. 12. Classification of DIABETES MELLITUS Type 1 β-Cell destruction Absolute insulin deficiency Autoantibodies Type 2 Other Gestational Islet cell autoantibodies Insulin autoantibodies Glutamic acid decarboxylase autoantibodies Tyrosine phosphatase IA-2 and IA-2B b autoantibodies 8/26/2013 12
  13. 13. Classification of DIABETES MELLITUS Type 1 Type 2 Insulin resistance with an insulin secretary defect Relative insulin deficiency Other Gestational 8/26/2013 13
  14. 14. Classification of DIABETES MELLITUS Type 1 Type 2 Other Gestational Associated with secondary conditions Genetic disease of β-cell function and insulin action Pancreatic disease Endocrine disease Drug or chemical induced Insulin receptor abnormalities Other genetic syndromes 8/26/2013 14
  15. 15. Classification of DIABETES MELLITUS Type 1 Type 2 Other Gestational Glucose intolerance during pregnancy due to metabolic and hormonal changes 8/26/2013 15
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  17. 17. This form of diabetes is immune-mediated in over 90% of cases and idiopathic in less than 10%. Polyuria, polydipsia, and weight loss associated with RPG200 mg/dL. FPG>126 mg/dl more than one occasion Islet autoantibodis are frequently present. 8/26/2013 17
  18. 18. Approximately one-third of the disease susceptibility is due to genes and two-thirds to environmental factors. Genes that are related to the HLA locus contribute about 40% of the genetic risk. • About 95% of patients with type 1 diabetes possess either HLA-DR3 or HLA-DR4, compared with 45–50% of white controls. 8/26/2013 18
  19. 19. Diagnostic sensitivity and specificity of autoimmune markers in patients with newly diagnosed type 1 diabetes mellitus. Sensitivity Specificity Glutamic acid decarboxylase (GAD65) 70–90% 99% Insulin (IAA) 40–70% 99% Tyrosine phosphatase (IA-2) 50–70% 99% Most patients with type 1 diabetes mellitus have circulating antibodies to islet cells (ICA), insulin (IAA), glutamic acid decarboxylase (GAD65), and tyrosine phosphatases (IA-2 and IA2-β ) at the time the diagnosis is made. 8/26/2013 19
  20. 20. • Less than 10% of subjects have no evidence of pancreatic β cell autoimmunity to explain their insulinopenia and ketoacidosis. It was recently reported that about 4% of the West Africans with ketosis-prone diabetes are homozygous for a mutation in PAX-4 (Arg133Trp)—a gene that is essential for the development of pancreatic islets. 8/26/2013 20
  21. 21. Most patients are over 40 years of age and obese. Polyuria and polydipsia. Ketonuria and weight loss generally are uncommon at time of diagnosis. Candidal vaginitis in women may be an initial manifestation. Many patients have few or no symptoms. Hypertension, dyslipidemia, and atherosclerosis are often associated. 8/26/2013 21
  22. 22. Autosomal dominant and an age at onset of 25 years or younger. Nonobese and impaired glucose-induced secretion of insulin. Mutations of a transcription factor that regulates islet gene expression. 8/26/2013 22
  23. 23. This is a very rare subtype of nonobese type 2 diabetes, with no more than ten families having been described. Since affected individuals were heterozygous and possessed one normal insulin gene, diabetes was mild, did not appear until middle age, and showed autosomal dominant genetic transmission. 8/26/2013 23
  24. 24. Defects in one of their insulin receptor genes have been found in more than 40 people with diabetes, and most have extreme insulin resistance associated with acanthosis nigricans. Diabetes due to mutant insulin receptors Insulin Receptors 8/26/2013 24
  25. 25. Impairs the transfer of leucine or lysine into mitochondrial proteins has been described. Most patients have a mild form of diabetes Diabetes mellitus associated with a mutation of mitochondrial DNA 8/26/2013 25
  26. 26. An autosomal recessive neurodegenerative disorder first evident in childhood. It is due to mutations in a gene WFS1, which encodes a 100.3 KDa transmembrane protein localized in the ER. Wolfram's syndrome DIDMOAD 8/26/2013 26
  27. 27. Individuals are at much higher risk for developing type 2 diabetes than insulin-sensitive persons also elevated plasma triglycerides, lower high-density lipoproteins (HDLs), and higher blood pressure Twenty-five percent of the general obese nondiabetic population has insulin resistance of a magnitude similar to that seen in type 2 diabetes. 8/26/2013 27
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  29. 29. Occurs during pregnancy as a result of hormonal influences causing insulin resistance 8/26/2013 29
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  31. 31. DIABETES MELLITUS Insulin↓ and glucagon↑ ↓Glucose uptake Hyperglycemia Glucosuria • Osmotic diuresis • Dehydration • Coma • Death ↑Protein catabolism ↑Plasma amino acids ↑Nitrogen loss in urine ↑Gluconeogenesis ↑Lipolysis ↑FFA oxidation ↑Ketogenesis • Ketosis • Coma • Death Metabolic events occurring in diabetes mellitus 8/26/2013 31
  32. 32. Clinical features of diabetes at diagnosis. Type 1 Diabetes Type 2 Diabetes Polyuria and thirst ++ + Weakness or fatigue ++ + Polyphagia with weight loss ++ – Recurrent blurred vision + ++ Vulvovaginitis or pruritus + ++ Peripheral neuropathy + ++ Nocturnal enuresis ++ – Often asymptomatic – ++ 8/26/2013 32
  33. 33. Between 1979-1997Before 1979 No uniform criteria NDDG&WHO Diagnostic criteria for Diabetes Mellitus 8/26/2013 33
  34. 34. 19991997 ADA WHO Diagnostic criteria for Diabetes Mellitus 8/26/2013 34
  35. 35. Since 1965 the WHO has published guidelines for the diagnosis and classification of diabetes. These were last reviewed in 1998 In addition, in 2003, the ADA reviewed its diagnostic criteria. ADA recommended lowering the threshold for IFG from 6.1mmol/l (110mg/dl) to 5.6mmol/l(100mg/ dl) 8/26/2013 35
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  39. 39. Paper strip impregnated with glucose oxidase and a chromogen system Sensitive to as little as 0.1% glucose in urine. Urinalysis 8/26/2013 39
  40. 40. By nitroprusside tests (Acetest or Ketostix). Do not detect β- hydroxybutyric acid Urinalysis 8/26/2013 40
  41. 41. Blood testing procedures Normal carbohydrate diet for 3 days Overnight fast on the day of the test FPG is drawn Give 75gm of anhydrous glucose in about 300ml of water Blood & urine specimens are collected at half hourly for 2hours A curve is plotted for time against blood glucose 8/26/2013 41
  42. 42. The Diabetes Expert Committee criteria for evaluating the standard oral glucose tolerance test.1 Normal Glucose Tolerance Impaired Glucose Tolerance Diabetes Mellitus Fasting plasma glucose (mg/dL) < 110 110–125 ≥126 Two hours after glucose load (mg/dL) < 140 ≥140–199 ≥200 Criteria for laboratory confirmation of diabetes mellitus Blood testing procedures 8/26/2013 42
  43. 43. The major form of HbA1 is hemoglobin A1c (HbA1c) where glucose is the carbohydrate. The remaining HbA1 species contain fructose-1,6 diphosphate (HbA1a1); glucose-6-phosphate (HbA1a2); and unknown carbohydrate moiety (HbA1b). Blood testing procedures 8/26/2013 43
  44. 44. Blood testing procedures Serum fructosamine is formed by nonenzymatic glycosylation of serum proteins (predominantly albumin). 8/26/2013 44
  45. 45. Capillary blood glucose measurements performed by patients themselves, as outpatients, are extremely useful 8/26/2013 45
  46. 46. DexCom system MiniMed system Glucowatch system 8/26/2013 46
  47. 47. Lipoprotein abnormalities in diabetes High serum triglyceride level (300–400 mg/dL), Low HDL cholesterol (less than 30 mg/dL), and Qualitative change in LDL particles, producing a smaller dense particle 8/26/2013 47
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  49. 49. Obese people have large amounts of the molecule CXCL5, produced by certain cells in fatty tissue "The CXCL5 molecule helps cause insulin resistance and type 2 diabetes". The finding has been published in the journal Cell Metabolism 8/26/2013 49
  50. 50. ACS' weekly newsmagazine Drug manufacturers have tried for years to develop oral insulin without much success. Several insulin pills are now in various stages of clinical trials 8/26/2013 50
  51. 51. Bianca van Lierop, Monash University and her colleagues have successfully strengthened insulin's chemical structure, which can withstand higher temperatures. A development that will bring relief to millions of diabetics across the world. 8/26/2013 51
  52. 52. "Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis," Appeared online June 27 in Nature Genetics. DNA variants that are associated with increased risk of type 2 diabetes, bringing the number to 38. 8/26/2013 52
  53. 53. From HbA1c May Be Useful for Diabetes Screening, Diagnosis in Routine Clinical Practice .Laurie Barclay, MD January 22, 2010January 12 issue of Diabetes Care. Diabetes Care Study authors write. "A high proportion of people with IA1c [impaired A1c] have abnormal glucose status requiring follow-up." "HbA1c provides a practical alternative for screening [that] is more convenient and reproducible than is blood glucose. "HbA1c <5.5% and >7.0% predicts absence or presence of Type 2 diabetes while at HbA1c 6.5-6.9%, diabetes is highly probable in clinical and population settings," 8/26/2013 53
  54. 54. In an experimental procedure called islet transplantation, islets are taken from the pancreas of a deceased organ donor. The islets are purified, processed, and transferred into another person. Once implanted, the beta cells in these islets begin to make and release insulin. Researchers hope that islet transplantation will help people with type 1 diabetes live without daily injections of insulin. 8/26/2013 54
  55. 55. CMDT 2010 Standards of Medical Care in Diabetes—2010 American Diabetes Association Internet 8/26/2013 55

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