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Diabetes Mellitus
Slides prepared by
Dr Ee Mun LimChemical Pathologist
Dr Vance Matthews
Learning Objectives
�What is Diabetes Mellitus? �Epidemiology �Classification & Pathophysiology
�Glucose metabolism �Type 1 & 2 DM
�Diagnosis �Symptoms & Complications �Management options
Continuum
ObesityInactivity
Insulin resistanceDiabetes mellitus
What is diabetes mellitus ???
• Diabetes is the name given to a group of chronic conditions (encompasses a wide clinical spectrum)
• characterised by – increase circulating blood glucose levels
(hyperglycaemia) due to– reduced or ineffective use of insulin(which is a hormone produced by the pancreas)
• Causing damage to tissues over time leading to life threatening health complications.
• There are 2 broad categories- Type 1 and Type 2 DM - 5-10% type 1
Why is it so important ?????
Diabetes Globally ……
• It is the world’s fastest growing chronic disease.
• 2006 – UN - diabetes as a major health crisis around the world
• T2DM has become one of the world's most important public health problems.
• 14th Nov – world DM day
World2011 = 366 million2030 = 552 million
TYPE 2 DIABETES IN AUSTRALIA
3.5xincreased
prevalence by 2051, if obesity and inactivity
rates continue to increase1
3xmore likely in Indigenous
Australians vsnon-indigenous
Australians1
Leading cause of end stage renal disease2
For Australians with diabetes or pre-diabetes, cardiovascular disease is
the leading cause of death (65% of all CV deaths)2
Prevalence rises with age: 14–16% of Australians aged >65 have been
diagnosed with diabetes2
1. Davis W et al. Intern Med J 2006; 36: 155–61. 2. Diabetes: the silent pandemic and its impact on Australia. Melbourne, VIC: Baker IDI Heart and Diabetes Institute, 2012.
Diabetes Tsunami
Few more important facts !!!
The greatest number of people with diabetes are between 40 to 59 years of age
78,000 children develop type 1 diabetes every year
Burden in Australia
• 280 Australians develop diabetes every day • Diabetes is Australia’s fastest growing chronic
disease• ~1,000,000 Australians are currently diagnosed with
diabetes. • For every person diagnosed, it is estimated that there
is another who is not yet diagnosed• 6th leading cause of death in Australia.• Diabetes is the leading cause of non-traumatic lower
limb amputation and end stage kidney disease
Burden in Australia…
• Type 2 DM costs Australia $3 billion per year - Average cost DM2 with no complications is $10,900 - Double the cost $20,525 if there are complications
• 4% people with diabetes account for 12% health costs in Australia - Australia's indigenous population suffers the 4th
highest rate of DM2 in the world
• Up to 60% of cases of type 2 DM can be prevented.
Normal Glucose
Homeostasis
Glucose is the major energy source & comes from food (simple
and complex carbohydrates)
Normal glucose homeostasis
• Action of insulin
• Glucose is stored as GLYCOGEN in liver and muscle
• This storage process is called GLYCOGENESIS
• Action of glucogan
• Liver glycogen is degraded between meals to maintain blood glucose levels
• Breakdown of glycogen to glucose is called GLYCOGENOLYSIS
Insulin
Glucogan
Classification &Pathophysiology
Classification
• Type 1 : 10%• Type 2 : 90% progressive disease• Gestational• Other specific forms – MODY (monogenic) • Secondary
– Insulin deficient due to pancreatic destruction/damage• Genetic Syndrome association
– CF, Myotonic dystrophy, Haemachromatosis– Insulin Resistant
• Endocrine disease – Cushings’, Acromegaly, Phaeochromocytoma
• Medication related– Steroids, Thiazides
Type 1 versus Type 2
• Type 1– earlier onset– 80% under the age of 10– unknown trigger– associated with
autoantibodies– assoc with other
autoimmune disease– Symptomatic on
presentation
• absolute insulin deficiency
• Type 2– usually later onset (>30 y.o.)– linked to obesity– assoc family history– Progresses– Often asymptomatic
• insulin resistant..– higher levels measured
insulin needed maintain normoglycaemia
Type 1 Diabetes Mellitus-Pathophysiology
GENETIC SUSCEPTIBILITYHLA genesAutoimmune RegulatorsAutoimmune predisposition
-Addison’s-Coeliac-Pernicious Anaemia-Thyroiditis
DAMAGEInfections?Food? (Cow’s milk, cereals)Something Else?
DIABETES
Decreasing beta cell mass
Natural history of type 1 DM
Non Autoimmune Diabetes due to Pancreas Destruction
• Trauma• Tumour
• Surgery• Cystic Fibrosis
• Pancreatitis (alcohol, drugs, infection, etc)
Type 2 DM Pathophysiology
• Complicated & not fully understood
• Dual mechanism – Insulin resistance
• higher levels measured insulin needed maintain normoglycaemia
– Insulin deficiency
Type 2 Diabetes Pathophysiology
Impaired insulin secretion
Hyperglycaemia
Increased HGP Decreased glucose uptake
DeFronzo RA. Diabetes 2009; 58:773–95.
ββββ-Cellsproduce
less insulin
αααα-Cellsproduce excess
glucagon
Pathogenic Defects in Type 2 Diabetes
Disease Progression with Deteriorating Islet Cell Function
Risk factors associated with Type 2 Diabetes Mellitus
• Family history • Age usually over 40 but
children and young adults now developing type 2
• History of Gestational Diabetes
• Excess weight• Aboriginality• Other specific ethnic groups
eg Chinese and those from Indian sub-continent
• Insulin resistance syndrome (Metabolic Syndrome )
Obesity Epidemic
• 14 millions are overweight or obese• If weight gain continues at current rate, 80% Aussie
adults and 1/3 children will be overweight or obese.• Obesity has overtaken smoking as the leading cause
of premature death and illness in Australia
Type 2 DM is PREVENTABLE!!!
T2DM is largely preventable…
8000 calories
Starting even younger...
Diagnosis
Risk factors for developing Type 2 Diabetes Mellitus
• Family history • Age usually over 40 but children and young adults
now developing type 2• All people with CVD• History of Gestational Diabetes• Excess weight• Aboriginality• Other specific ethnic groups eg Chinese and those
from Indian sub-continent• Insulin resistance syndrome (Metabolic Syndrome )
Tools for diagnosis
• Glucose level (BSL)– mmol/l– Fasting /Random
• Oral glucose tolerance test – 75g of glucose– Fasting, 30min, 60min
plasma glucose
Tools of diagnosis
• HbA1c (Glycated Haemoglobin)– It is formed in a non-enzymatic glycation pathway
by haemoglobin's exposure to plasma glucose
– The HbA1c level is proportional to average blood glucose concentration over the previous 4 wks to 3 months
– Diagnostic tool • No requirement for pretest fasting • DM if HbA1c ≥ 6.5%
Current Australian Guideline for Screening MJA 2003 Vol79: 379-383
Current Australian Guideline for Screening MJA 2003 Vol79: 379-383
HbA1c ≥6.5% (48 mmol/mol)
Are there limitations?
Practicality of HbA1c
• Non-fasting, random sample
• Patient’s preparation not required• Not affected by short-term lifestyle changes
• Abnormal fasting glucose or OGTT not F/U• Correlation with microvascular complications
• Point of care, whole blood specimen• Physicians familiar with HbA1c in diabetes
monitoring
Saudeck et al. JCEM 2008;93:2447
Type 1 versus Type 2
• Type 1– earlier onset– unknown trigger– associated with
autoantibodies– assoc with other
autoimmune disease
• absolute insulin deficiency
• Type 2– usually later onset– linked to obesity– assoc family hx– progresses
• insulin resistant..– higher levels measured
insulin needed maintain normoglycaemia
Symptoms of DM
Acute Complications
• Diabetic Ketoacidosis (DKA)Usually occurs in Type 1 but may be seen in Type 2s
• Hyperglycaemia Hyperosmolar state– Type 2 DM
• Hypoglycaemia – Occurs as a result of therapy
Long term complications• Microvascular
– DM retinopathy• Non proliferative • Proliferative • Macular edema
– Nephropathy• Micoralbuminuria• Macroalbuminuria• End stage renal failure
– Neuropathy • Autonomic neuropathy • Peripheral neuropathy • Erectile dysfunction
Macrovascular complications
– Cerebrovascular• TIA• Stroke
– Cardiovascular• Angina • IHD • Heart failure
– Peripheral vascular disease
• Gangrene
Treatment of
Diabetes Mellitus
Why treat ??
• Prevent complications
• Risks of the main complications of diabetes decreased with approximately 3% for every 1 mmol/mol decrease in HbA1c
Treatment of DM
• Multidisciplinary approach
• Aim to prevent complications• Aggressive treatment
– Achieve glycaemic control– Target Blood Pressure and
– Target lipid profile (cholesterol)
Treatment Aims• Aggressive treatment of glycaemic control, BP,
lipids +/- Aspirin
• Targets Diabetes Australia� HbA1c <7% (in Europe reduced to <6.5% evidence shows increase d hypos)
� TC<4.0, TGs<2.0, HDL >1.0, LDL<2.5mmol/L� BP <130/<80mmHg
• <125/75 with proteinuria >1g/day
• Target Blood Glucose Level :� Fasting 4-6 mmol/L� <8 prior to meals� <8 (-10) before bed
Treatment of Diabetes Mellitus
• T1DM have an absolute insulin deficiency
�Exogenous insulin is needed• or a new Pancreas!
Transplant …
• Pancreas transplant
• Islet cell transplant
Lifestyle changes
Adapted from Riddle MC. Endocrinol Metab Clin North Am 2005; 34:77–98.
Diet and exercise
Oral monotherapy
Standard approach to the management of T2D: treatment intensification
Oral combination ++
Oral + insulin ++ ++
Insulin
Thank you !
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