Diabetes mellitus An overview. Dr.Prasad Katulanda MBBS, MD, Dphil Consultant Endocrinologist/diabetologist Senior Lecturer in Medicine

Transcription

1 Diabetes mellitus An overview Dr.Prasad Katulanda MBBS, MD, Dphil Consultant Endocrinologist/diabetologist Senior Lecturer in Medicine ASCEND 2011

2 Objectives Definition Magnitude of the problem & Epidemiology Clinical presentations Diagnosis Classification of Diabetes mellitus Natural History of Diabetes and Pre-diabetic states Characteristics of the Asian diabetes epidemic

3 Definition of Diabetes Mellitus

4 Definitions Diabetes mellitus Chronic hyperglycaemia Acute metabolic complications Chronic organ dysfunction and failure

5 Global pandemic of diabetes, million with diabetes International Diabetes Federation, World Diabetes Atlas 2009

6 Prevalence (%) estimates of diabetes (20-79 years), million with diabetes

7 Prevalence (%) estimates of diabetes (20-79 years), 2010 South-East Asian Region

8 Regional estimates for diabetes, 2010 International Diabetes Federation, World Diabetes Atlas 2009

9 Number of people with diabetes (20-79 years), 2010 and 2030 International Diabetes Federation, World Diabetes Atlas 2009

10 Epidemic in South Asia National Urban Rural India Sri Lanka Pakistan Bangladesh Ramachandran et al. lancet, 2009

11 Asian Disease

12 Implications - multisystem disease

13 Impact of the disease Western Data Commonest cause of ESRF Commonest cause of new onset blindness Commonest cause of non traumatic lower limb amputation Stroke adult disability Cardiovascular disease Mortality Statistics - underestimate Health Care Costs unbearable to developing nations The most burdensome chronic disease of the New millennium (WHO)

14 Diagnosis of Diabetes Mellitus Prevalence of retinopathy according to plasma glucose and HBA 1C levels [ 2 hr plasma glucose, fasting plasma glucose, HBA 1C. Based on data from Pima Indians - adapted from Diabetologia (McCance et al., 1997)]

15 Diagnosis of Diabetes Mellitus DIABETES 1. SYMPTOMS OF DIABETES PLUS CASUAL PLASMA GLUCOSE 11.1 MMOL/L ( 200MG/DL). CASUAL REFERS TO ANY TIME OF THE DAY REGARDLESS OF THE RELATIONSHIP TO MEALS. CLASSIC SYMPTOMS OF DIABETES INCLUDE POLYURIA, POLYDIPSIA AND WEIGHT LOSS. ADA 1997, WHO If no symptoms need repeating OR 1. FASTING PLASMA GLUCOSE 7MMOL/L ( 126MG/DL). FASTING DEFINED AS NO CALORIC INTAKE FOR MORE THAN 8 HOURS. OR 1. 2 HOUR PLASMA GLUCOSE 11.1 MMOL/L ( 200MG/DL) DURING AN OGTT. IMPAIRED GLUCOSE TOLERANCE (IGT) 2 HOUR PLASMA GLUCOSE 7.8 MMOL/L (140MG/DL) AND 11.1 MMOL/L (200 MG/DL) AND FASTING GLUCOSE <7MMOL/L (IF MEASURED) IMPAIRED FASTING GLUCOSE (IFG)* FASTING PLASMA GLUCOSE MMOL/L ( MG/DL) AND 2 HOUR PLASMA GLUCOSE < 7.8 MMOL/L (IF PERFORMED)

16 Diabetes mellitus

17 Diagnosis of categories of glucose intolerance Fasting plasma glucose 2-Hour PG plasma glucose 7 mmol/l Diabetes mellitus 11 mmol/l Diabetes mellitus Impaired fasting glycaemia Prediabetes Impaired glucose tolerance <5.6 mmol/l Normal <7.8 mmol/l Normal

18 Importance of pre-diabetes Higher percentage progress to diabetes mellitus Theoretically should be able to prevent progression to diabetes High risk of cardiovascular disease

19 Risk of progression to hyperglycaemia 5-10% progress to diabetes on an annual basis (0.7% in Nl) Gerstein HC et al Diabetes Res Clin Pract 2007; 78:

20 Glycaemia and CVD risk DECODE Study. Diabetes Care 2003; 26:

21 Clinical Presentations Asymptomatic Acute symptoms Subacute presentation Presentation with complications

22 Acute presentation Brief history over 2-4 weeks Classic triad polyuria, polydipsia, weight loss Ketoacidosis Especially seen in Type 1 Diabetes

23 Sub-acute presentation Symptoms over several months Non specific symptoms lack of energy, visual blurring Polyuria, Nocturia Pruritus vulvae, balanitis Type 2 diabetes commonly presents like this

24 Presentation with chronic complications T2DM Microvascular Nephropathy Neuropathy Retinopathy Macrovascular IHD, Stroke, PVD Other Infections Staphylococcal skin sepsis, wound infection, fungal infections

25 Types of Diabetes Mellitus 1. Type 1 2. Type 2 3. Other specific types 4. Gestational Diabetes Mellitus

26 Type 1 Diabetes Mellitus Immune mediated destruction of beta cells Absolute insulin deficiency Autoantibodies can be detected Associated with other autoimmune disease Leads to Keto-acidosis Younger onset <30 years Usually lean patients Genetic association less than for type 2

27 Type 1 Diabetes evidence for an autoimmune basis HLA associations HLA DR3/DR4 & DQ B increases the risk. HLA DR2 protective Presence of auto antibodies Islet cell antibodies (ICAs) Anti GAD antibodies Anti insulin antibodies Association with other autoimmune disease Pernicious anaemia, Autoimmune thyroid disease, Addisons diasease Immune suppression therapy can delay the onset Presence of T cell infiltration - insulitis

28 Type 2 Diabetes Mellitus (90 95% of all Diabetes) Previously called NIDDM Due to variable degrees of relative insulin deficiency and insulin resistance at tissue levels Usually seen in obese patients C peptide persist even at late stage Keto acidosis rare No specific HLA associations Strong genetic predisposition Can be asymptomatic until complications arise No insulitis

29 Risk factors for type 2 diabetes mellitus Non modifiable Age Genetic factors

30 Risk factors for type 2 diabetes Modifiable IGTI FG

31 Are you at risk of T2DM? 1. Have you got a first degree relative? 2. Are you from a high risk ethnic group? 3. Are you obese? 4. Are you spending a sedentary lifestyle? 5. Do you eating high calory fatty foods? 6. Do you a smoke? 7. Have you got hypertension? 8. Are you always stressed? 9. Did you have a low birth weight? How many risk factors you have got?

32 Other specific types of DM A. Genetic defects of Beta cell function B. MODY type 1-3, Mitochondrial DNA diasease C. Genetic defects in Insulin action D. Diseases of exocrine pancreas E. Other endocrinopathies F. Drug induced G. Infective H. Other genetic syndromes sometimes associated with DM

33 Gestational diabetes mellitus Diabetes occuring during pregnacy Associated with adverse maternal and foetal outcomes Can be a risk factor for development of Type 2 diabetes later in life

34 Risk factors for diabetes in Sri Lanka Age Physical inactivity Obesity Gestational diabetes Family history Low HDL cholesterol High triglycerides Hypertension Province of residence Overseas employment Acanthosis nigricans Katulanda et al

35 Pathogenesis of type 2 diabetes At risk environment - foetal to adulthood Excess calory intake Genetic predisposition Physical inactivity Obesity (visceral) Excess FFA β cell Lipotoxicity Insulin resistance Compensatory hyperinsulinaemia Beta cell secretory failure β cell Glucotoxicity Hyperglycaemia (T2DM)

36 How can we face this challenge? Normal Pre-diabetes IGT IFG Natural History of Type 2 Diabetes Clinical-diabetes Type 2 Diabetes Complications Disability Death Preclinical state Clinical disease Complications Primary prevention Secondary prevention Tertiary prevention

37 Primary prevention of T2DM

38 Lifestyle modification The Finnish Diabetes Prevention Study (DPS) Intensive lifestyle intervention in 577 with IGT Weight reduction >5% Reduced fat intake <30% Reduced saturated fats <10% Increased fiber content >15g/1000kCal Physical Exercise >30 min/day Type 2 diabetes reduced by 58% No new type 2 diabetes if all goals achieved N Eng J Med 344: , 2001

39 Lifestyle and Drugs Diabetes Prevention Program DPP In USA in people with IGT Intensive Lifestyle Modification 58% reduction Metformin 31% reduction N Eng J Med 344: , 2001

40 Drugs in primary prevention (?prevention) STOP-NIDDM Trial Acarbose DREAM study Rosiglitazone Xendos Orlistat 32% relative risk reduction Diabetes Care 21: , % relative risk reduction 2002Lancet (2006); 368: % relative risk reduction Diabetes 51: ,

41 Practical approaches 1. Population based approach Small changes in many people 2. High risk approach Bigger changes in small groups

42 Lifestyle intervention in prevention of T2DM

43 Overview of Management Aims of management Cure Relieve symptoms Prevent or delay long term complications Control other risk factors Patient Education and self management Reduce disability due to complications Improve quality of life

44 Specific aspects Glycaemic control Diet Exercise Oral hypoglycaemic agents/ Insulin Screening for complications Reduction of the cardiovascular risk Promotion of self care Mutlidisciplinary teamwork approach

45 Glycaemic Control Glycaemic control Tight control near normal Good evidence DCCT & UKPDS trials reduce and prevent microvascular complications + some positive effect on macrovascular Cx Reduction of the cardiovascular risk Promotion of self care Mutlidisciplinary teamwork approach

46 Glycaemic control

47 UKPDS

48 Hypertension control

49 When to optimise therapy? UKPDS post study monitoring glycaemic memory Accord high mortality esp if rapidly optimised in old and CVD pts ADVANCE better if slow and steady

50 UKPDS post study monitoring

51 UKPDS post study monitoring

52 UKPDS post study monitoring

53 UKPDS post study monitoring

54 UKPDS post study monitoring

55 UKPDS post study monitoring

56 DCCT trial

57 Diabetes in Asia Asia has undergone marked economic and demographic transition in recent decades Increasingly aging populations, globalization and industrialization are seen in most Asian Societies Changes seen in food supply and dietary patterns All these leading to epidemiological transition with diabetes, obesity, dyslipidaemia and related CVD morbidity and mortality becoming major public health concerns

58 Impact of migration

59

60 Characteristics of the Asian Diabetes Epidemic

61 South Asia rapid increase in prevalence Kun-Ho Yoon et al Lancet.com Vol 368 November 11, 2006

62 Age and diabetes V.U. Menon et al. /Diabetes Research and Clinical Practice 74 (2006)

63 Number of Persons With Diabetes in Different Age Groups Different Regions of the World in 2007 Chan, J. C. N. et al. JAMA 2009;301:

64 South Asian Diabetes occurs at lower level of obesity Kun-Ho Yoon et al Lancet.com Vol 368 November 11, 2006

65 Urbanisation and diabetes

66 Economic development and diabetes in Asia Lancet DOI: /S (09) India China Malaysia Singapore

67 BMI and diabetes - Caucasians Body mass index at 16 yr follow-up and relative risk for type 2 diabetes in participants in nurses' health study. Ann Intern Med 1995;122:481-6

68 South Asians have higher adiposity Identical BMI, but differences in body fat according to DEXA. Lifestyle, genetics or intrauterine factors?

69 BMI and diabetes Sri Lankans 25% Diabetes prevalence according to BMI 20% 19.30% 19.00% 15% 10% 9.80% 5% 4.20% 4.40% 0% < >=27.5 Sri Lanka Diabetes and CVD study

70 Aetiology Insulin resistance Age Obesity Physical inactivity Urbanisation Genetics ethnicity Other

71 Biochemical attributes of different ethnic groups living in Singapore Dickinson S, Colagiuri S, Faramus E, Petocz P, Brand-Miller JC. Postprandial hyperglycemia and insulin sensitivity differ among lean young adults of different ethnicities. J Nutr. 2002;132(9):

72 pmol/l Fasting and OGTT Insulin in different ethnicities Insulin (F) Insulin (2hr) Increment Caucasian SE Asian Chinese Indian Arabic Dickinson S et al Postprandial hyperglycemia and insulin sensitivity differ among lean young adults of different ethnicities. J Nutr. 2002;132(9):

73 HOMA IR Insulin resistance in different ethnicities Caucasian Chinese Indian Arabic Dickinson S et al Postprandial hyperglycemia and insulin sensitivity differ among lean young adults of different ethnicities. J Nutr. 2002;132(9):

74 Genetics - GWAs PPARG KCNJ11 TCF7L2 SCL30A8 CDKL1 HHEX IGF2BP2 CDKN2A CDKN2B FTO

75 Genetics Most variants confer similar risk as in Caucasians Interethnic differences in allele frequency (TCF7L2) Presence of other variants within the same gene Differences in the population attributable risks Need to conduct Asian relevant genetic studies

76 If not genes then what? Environmental pollution? Infections? Epigenetics?

77 Phenotypes of Asian Diabetes Epidemic

78 Aetiology Insulin requiring diabetes 4% Insulin Non-insulin Katulanda et al, Diabet Med, 25,

79

80

81 Aetiological subtypes of diabetes among young adults MIDD Type 1 LADA GAD -ve T1 Type 2 Katulanda, et al. Diabet Med, 25,

82 Societal impact

83 Number of Deaths Attributable to Diabetes in Different Regions of the World in 2007 Chan, J. C. N. et al. JAMA 2009;301:

84 Number of deaths attributable to diabetes, 2010 International Diabetes Federation, World Diabetes Atlas 2009

85 Mean health expenditure per person with diabetes (USD), R=2, 2010 International Diabetes Federation, World Diabetes Atlas 2009

86 Summary World especially Asia is facing a large epidemic of diabetes The diabetes prevalence is higher despite lower levels of obesity and income compared to the NA and Europe Diabetes most often affects people in Asia 10 years younger than in the West Despite lower level of income obesity is rapidly increasing in the South Asia

87 Implications of the diabetes epidemic Epidemic of diabetes related chronic complications blindness, renal failure, foot amputations Epidemic of CVD Consequences for affected individuals, families, health care services, the economy and society

88 Summary Glycaemic control is of paramount importance Tight blood pressure control saves lives Weight reduction and moderate exercise have multiple beneficial effects Optimise early start even at pre-diabetes stage Comprehensive CVD risk reduction is vital

89 Future of diabetes in Asia Urgent public health interventions to stem the tide of diabetes Modification of the health care systems to tackle diabetes and obesity related morbidity micro and macro vascular disease Further research Pathogenesis and specific genetic variants Practical and cost effective methods for early detection and prevention of diabetes

90

91