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 !