OVERVIEW OF DIABETES MELLITUS (TYPE 2)

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OVERVIEW OF DIABETES MELLITUS (TYPE 2)

• Bhushan Ghoorbin

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St Vincent Declaration (WHO 1989)

• 1. Reduce new blindness due to diabetes by one
  third or more
• 2. Reduce the number of people entering end-stage
  diabetic renal failure by at least one third
• 3. Reduce the rate of limb amputation for
  diabetes gangrene by a half
• 4. Cut morbidity and mortality from coronary
  heart disease in the diabetic by vigorous
  programmes of risk factor reduction
• 5. Achieve pregnancy outcome in diabetic women
  that approximates to that of non-diabetic women

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St Vincent Declaration

• 2 Reduce the numbers of people entering end-stage
  diabetic renal failure by at least one third

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St Vincent Declaration

• 3 Reduce the rate of limb amputation for diabetic
  gangrene by half

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St Vincent Declaration

• 4 Cut morbidity and mortality from coronary heart
  disease in the diabetic by vigorous programmes of
  risk factor reduction

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St Vincent Declaration

• 5. Achieve pregnancy outcome in diabetic women
  that approximates to that of non-diabetic women

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Prevalence

• Total population 3
• gt60 yrs 6
• South Asian (40-75 yrs) 20 30
• gt 1.2 million in UK 85 90 type2
• 3 million by 2010
• 1 million undiagnosed (WHO)

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The Problem - UK

• 2001 5 total NHS resourses
• 10 inpatient resourses
• Blood kit 90
  million
• Oral hypoglycaemic 64 million
• (20 increase on 2000)

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Local Issues

• Population MSW 82 white
• 18 ethnic
  minority
• Projected 2011 gt2 increase on 1999
• Ethnic minority distribution
• Wandsworth 22
• Merton 21
• Sutton 8
• Diabetes mellitus prevalence 2.75

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Classification and Terminology

• IDDM and NIDDM no longer used
• Type1 destruction of pancreatic B cells
• autoimmune
• Type2 Insulin resistance insulin
• not working properly /
  insensitivity
• of tissues to the actions of
  insulin

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Diagnostic criteria (WHO 2000)

• Fasting plasma glucose gt7mmol / L
• Random plasma glucose gt11.1
• 2 hrs plasma glucose (GTT) gt11.1
• Impaired fasting glucose gt6.1 lt7.0
• Impaired glucose tolerance gt7.8 lt11.1
  

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New diagnostic criteria

• With no symptoms requires 2 abnormal test
  results on two different days
• If diabetes is suspected in a child refer
  IMMEDIATELY to hospital diabetes team

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Impaired fasting glucose

• FBG gt6.1 but lt7.0 mmol / L
• Risk category for future diabetes
• - increased hepatic glucose production
• - impaired insulin secretion
• Lifestyle advice and annual surveillance

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Impaired Glucose Tolerance

• FBG lt7.0 mmol / L
• OGTT 2 hrs gt7.8 but lt11.1 mmol / L
• - Insulin resistance
• Prevalence 7 17
• 6 10 times developing diabetes
• Increased cardiovascular problems
• OGTT Gold standard 75 gms glucose load
• Lifestyle advice and annual surveillance

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Risk factors The serious seven

• 1. Lifestyle weight , exercise , smoking
• 2. Hyperglycaemia
• 3. Hypertension
• 4. Dyslipidaemia
• 5. Microalbuminuria
• 6. Retinopathy
• 7. foot problems

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Type2 DM characteristics at onset

• 100 hyperglycaemic and elevated FFAs
• 80 are obese
• 80 have fasting hyperinsulinaemia
• 50 are hypertensive
• 50 have dyslipidaemia
• 30 have macrovascular complications
• 15 have retinopathy
• 15 have neuropathy
• 5 have nephropathy

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Oral agents

• Traditional therapies
• Metformin
• Sulphonyl ureas
• Acarbose

• Newer therapies
• Glitazones eg
• rosiglitazone
• pioglitazone
• Prandial regulators
• Repaglinide
• Nateglinide

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Treatment of Obese Type2 DM

• STEP1 - DIET
• Lifestyle modification diet and exercises to
  reduce CVS risk factors
• .. BUT progressive

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Treatment of Obese Type 2 DM

• STEP 2 - Metformin
• Improves Insulin resistance
• No risk of hypos
• Improves mortality
• No weight gain
• Cheap
• Aspirin / ACE-I / B- blockers /Statins

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Treatment of Obese Type 2 DM

• STEP 3 MF SU
• Patient not adequately controlled on MF / unable
  to tolerate dose
• eg Glimepiride - once daily (min weight
  gain)

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Treatment of Obese Type 2 DM

• STEP 4 MF new drug
• Consider glitazone to improve insulin resistance
• Consider prandial regulator to improve PPG peaks

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GLITAZONES

• ROSIGLITAZONE
• 4mg daily
• Not monotherapy
• Only after trial of MFSU

• PIOGLITAZONE
• 30mg daily
• Not monotherapy
• Only after trial of MFSU

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GLITAZONES other benefits

• Lipid subfractions
• HDL2,HDL3 up
• Small dense LDL particles become larger and less
  atherogenic
• FFA level falls

• Urinary albumin
• 26 decrease with rosiglitazone at 12 m
• Blood pressure
• Falls by 3.5 / 2.7
• Clotting factors
• CRP fall

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GLITAZONES - questions

• Good evidence that addition to MF or SU better
  than MF or SU alone
• Triple therapy?
• Monotherapy?
• Insulin?

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GLITAZONES NICE recommendations

• Only use in combination with MF or SU
• Where BG remains high despite adequate trial of
  MT SU

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GLITAZONES delayed onset

• Max effect may take weeks months
• May see BG deteriorate initially as SU /MF stopped

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Prandial regulators

• Meglitines repaglinide Novonorm
• Phenylalanine derivative nateglinide starlix
• Low risk of hypoglycaemia
• Increase Insulin secretion within 15 mins of meal
• Stimulate early phase Insulin response to food

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Prandial regulators

• With SU NO
• Ineffective after SU depletes beta cells of
  Insulin
• With MF YES
• With Glitazones Unlicensed
• Limited data on 75 yrs

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DO NOT

• Insulin Glitazone
• SU Prandial regulator
• Glitazone Prandial regulator
• SU SU

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Non- obese Type2 DM

• STEP2 SU
• eg gliclazide bd
• or glimepiride if compliance poor
• STEP 3 -5 as for obese

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Non-obese Type2 DM

• May be slow onset Type1
• More likely to require Insulin eventually
  especially if ve islet cell antibodies or ve
  GAD antibodies

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Insulins

• Rapid acting analogues
• Insulin lispro - Humalog
• Insulin aspart Novorapid
• Long acting analogues
• Insulin glargine
  Lantus
• Insulin detemir -
  Levemir

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Decisions

• Obese vs thin
• Ketones
• Metformin tolerance
• Risk of hypos
• Renal function
• Cardiac function
• Patient choice
• Evidence

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• Thank you