Diabetes mellitus

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Diabetes mellitus

• Dr. med. Robert Ostermann-Myrau
• Diabetologist DDG
• Medical Director Gen Re

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Main risks of Diabetes mellitus

• Macrovascular
• Increased risk of atherosclerosis
• Increased myocardial infarction rate
• Increased stroke rate
• Applies both for incidence and for prognosis
  after contracting disease

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Main Risks of Diabetes mellitus

• Microvascular
• Nephropathy
• Neuropathy
• Retinopathy

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Causes of Atherosclerosis
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What is special about Diabetes

• Hyperglycaemia
• Hyperinsulinaemia
• Dyslipidaemia
• Endothelial dysfunction
• Alteration of the coagulation system

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What happens

• Endothelial dysfunction
• Increased endothelial permeability
• Activation and increased expression of adhesion
  molecules (Vcam-1)
• Chemokine-induced migration of inflammatory cells

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What happens

• Vascular walls
• Limited endothelial-dependent vasodilatation and
  reduced separation of NO from the endothelium
• Coagulation system
• Loss of antithrombogenic and increase of
  thrombogenic factors

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What happens

• Fatty-streak formation
• Monocytes phagocytose the migrant lipids
• Pro-inflammatory cytokines and growth factors are
  released
• Smooth muscle cells proliferate in the intima
• Lipid core becomes necrotic, macrophage/foam-cell
  enzymes cause thinning of the capsule

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What is special about Diabetes

• Necrotic part in the core of the plaque is bigger
• Increased numbers of macrophages and foam cells
• Higher plaque instability

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In Pictures
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False Security

• Two-thirds of all myocardial infarcts result from
  coronary stenoses less than 50
• Fewer than 15 of myocardial infarcts result from
  coronary stenoses greater than 75

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Diabetes and Kidney Damage

• After 20 years of diabetes, nephropathy is found
  in 20-40 of cases
• Renal risk is about the same for Types 1 and 2 if
  they dont die of other reasons
• (Hasslacher, C 1989)

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Distribution of renal damage in Type 2

• 60 presented as Kimmelstiel-Wilson
• 15 vascular damage
• 25 kidney disease independent from diabetes

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Renal biopsy with microalbuminuria

• Always typical changes with proteinuria!

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Type 2 with microalbuminuria

• Risk of myocardial infarct doubled
• Renal function worsens in approx. 80 of cases,
  if not cardiovascular death occurs first

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Type 2 with microalbuminuria

• microalbuminuria

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Pathophysiology

• Reduced protein expression in kidney podocytes
• AT2 level suppressed, but good response to AT1
  blockers
• Damaged kidneys express intrarenal AT2

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The risk in figures

• Heart Protection Study
• 20536 people in total, of whom 5963 have Diabetes
  mellitus. Aim Simvastatin vs. placebo, average
  length of treatment 4,8 years
• Data collection 1994-97 age included 40-80
  years
• Average age of Diabetes Group 62 years average
  duration of diabetes 25 years no CAD in 50

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The risk in figures

• Heart Protection Study

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The risk in figures

• Heart Protection Study
• Risk of a vascular event in diabetes without
  previous manifest cardiovascular disease
• 13.5 in 5 years 27 in 10 years ?
• all diabetics
• 20 in 5 years 40 in 10 years ?

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The risk in figures

• MONICA-Study
• City and District of Augsburg, District of
  Aichach-Friedberg
• 1985 1990 and 1995, cross-sectional data of
  people aged 25-74 with question of prevalence of
  cardiac risk factors
• Height, weight, blood pressure
• Interview
• Blood sample (mainly non-fasting)

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The risk in figures

• MONICA-Study
• 1998 Survival status of all participants
  determined
• Questionnaire on health and diabetes in
  particular (Y/N)
• Since 1985, all patients with myocardial
  infarctions have been followed-up in up to 20
  hospitals
• Death certificates from the region were matched
  with GP enquiries

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The risk in figures

• MONICA-Study
• Diabetes mellitus was reported by patient
• Not all diabetics were diagnosed!!

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The risk in figures

• MONICA Survey
• 13428 participants, 552 with Diabetes mellitus,
  follow-up 22 years, risks age-adapted
• With diabetes the risk of myocardial infarction
  compared with the non-diabetes group increased by
  a factor of
• Men 3.7
• Women 5.9

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The risk in figures

• MONICA-Survey-Lifestyle
• Men DM/- Women DM/-
• Smoker () 28.4 / 28.4 10.1 / 16.6
• Little physical activity () 67.3 / 58.3 79.0 /
  63.5
• Obesity () 38.9 / 19.8 44.4 / 21.4
• Hypertension () 46.2 / 25.9 53.6 / 21.2
• Cholesterol gt 240 mg () 49.9 / 46.6 58.5 /
  43.5

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The risk in figures

• MONICA-Survey-Lifestyle
• High BP, obesity, hypercholesterolaemia increased
  by a factor of
• Men 1.3 2.3
• Women 2.1 3.3
• Five-year mortality for patients after myocardial
  infarction compared to non-diabetics increased by
  a factor of
• 1.6 (Data from 1985-92)

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The risk in figures

• Decrease in life expectancy
• Mecklenburg for recently diagnosed diabetes, over
  30 years 5.3 yrs for men, 6.4 yrs for
  women Schneider et al, 1993
• NHANES 8 years for age 55-64 4 years for age
  65-74 Gu et al, 1998
• Diabetes Type 1 with nephropathy life expectancy
  of 14 years in 1980s Rossing et al, 1996

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The risk in figures

• UKPDS
• 3867 newly diagnosed type-2 diabetics, randomized
  into a basic and an intensive therapy arm
• 10-year follow-up
• 3055 patients examined for CAD risks 335
  contracted CAD in 10 years (12, average age 52
  years)

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The risk in figures

• PROCAM
• 33000 participants, initiated 1978, employees of
  large businesses in Münster aged 16-65, one-third
  of them women
• Calculation of the probability of suffering a
  myocardial infarct in the next 10 years
• Average age of the diabetics 51 years

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The risk in figures

• Are you male or female?
• How old are you (in years)?How is your LDL
  cholesterol (bad cholesterol)?How is your HDL
  cholesterol (good cholesterol)? How are your
  (fasting) triglycerides? How is your systolic
  blood pressure?Have you smoked cigarettes in the
  last 12 months?
• Do you have Diabetes mellitus?Has a
  first-degree relative of yours (father, mother,
  brother, sister, son, daughter) suffered a heart
  attack before the age of 60? www.chd-taskforce
  .de

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The risk in figures

• PROCAM Calculator
• 45-yr-old man, LDL 140, HDL 40, TG 120, BP 130
  syst., non-smoker, no diabetes, no family risk
• Risk of heart attack in next 10 years 2
• 45-yr-old man, LDL 140, HDL 40, TG 120, BP 130
  syst., non-smoker, Type-2 diabetes, no family
  risk
• Risk of heart attack in next 10 years 5
• 45-yr-old man, LDL 140, HDL 40, TG 120, BP 130
  syst., Smoker, no diabetes, no family risk
• Risk of heart attack in next 10 years 4

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Disturbed Glucose Tolerance

• IFG (impaired fasting glucose)
• Fasting blood glucose above 125 mg in whole
  blood
• IGT (impaired glucose tolerance)
• Blood glucose 2 hrs. after 75 g glucose 140 - 200
  mg

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Disturbed Glucose Tolerance

• Kora Survey 2000
• 1353 patients over 55

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Disturbed Glucose Tolerance

• KORA Survey 2000
• Overall, 40 of the Augsburg population between
  55 and 74 years of age suffer from disturbed
  glucose metabolism
• If the relative risk of cardiovascular events for
  Diabetes mellitus stands at 2, it stands at 1.7
  for IFG or IGT!

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To sum up...

• CAD in Diabetes mellitus is an early damage
  time period not suitable as a predictor of risk
• Similar mortality for Types 1 and 2 (Type 1
  renal, Type 2 cardiac)
• Vascular events in the next 10 years
• HPS 25
• MONICA 5 M 1 F
• PROCAM 11 coronary, 3.6 cerebral events in
  non-diabetics 6