What is diabetes?

Diabetes mellitus (DM) Diabetes mellitus is a serious

metabolic condition and one of the worlds leading chronic
diseases, affecting more than 381 million adults worldwide
~8% of the worlds adult population (Guariguata, Whiting
et al. 2014; Boyle, Honeycutt et al. (2001); AIHW 2013).
Diabetes mellitus is characterised by hyperglycemia
resulting from defects in insulin secretion, insulin action, or
both

Why Is Diabetes a Problem?

Glucose

Glucose is a type of sugar major fuel for body

Glucose is broken down from foods (i.e. carbs) where it passes into body
cells and used for energy.
Glucose molecules cant just pass into cells they have to wait outside
until someone realises they are stood there waiting THIS IS THE JOB
OF INSULIN.

The role of glucose and insulin

Insulin is a hormone made by the beta cells in the pancreas.

Lack of insulin can be absolute none at all
Relative when normal level of insulin is made, but insulin is

not effective.

Types of diabetes
There are two main types of diabetes Type 1
and Type 2 (written as t1DM and t2DM) and
several subtypes

Other types:
LADA (Latent Autoimmune Diabetes of Adulthood)
MODY (Maturity-Onset Diabetes of Youth)
Secondary Diabetes Mellitus
Gestational Diabetes

Signs and symptoms Of diabetes

The pathogenesis of type 1 and type 2

diabetes are very different

Type 1 diabetes
Was previously called insulin-dependent diabetes

mellitus (IDDM) or juvenile-onset diabetes.

This form of diabetes usually strikes children and

young adults, although disease onset can occur at

any age.
Type 1 diabetes may account for 5% to 10% of all

diagnosed cases of diabetes.

Must be treated with insulin.

T1DM - Etiology
Type 1 diabetes develops when the bodys immune

system destroys pancreatic beta cells, the only cells

in the body that make the hormone insulin that
regulates blood glucose.
Viral infection
Genetic tendency
Development of antibodies
Certain drugs and chemicals

Type 2 Diabetes

T2dm etiology
Risk factors for type 2 diabetes

Four of the main risk factors for developing type 2

diabetes are:
age being over the age of 40 (over 25 for South Asian
people)
genetics having a close relative with the condition
(parent, brother or sister)
weight being overweight or obese
ethnicity being of South Asian, Chinese, AfricanCaribbean or black African origin (even if you were born in
the UK)

Type 2 DM Pathophysiology

Insulin resistance
Beta cell dysfunction

Burden of Type 2 Diabetes

The development of diabetes is projected to reach pandemic

proportions over the next10-20 years.

International Diabetes Federation (IDF) data indicate that by

the year 2025, the number of people affected will reach 333
million 90% of these people will have Type 2 diabetes.
In most Western societies, the overall prevalence has

reached 4-6%, and is as high as 10-12% among 60-70-yearold people.

The annual health costs caused by diabetes and its

complications account for around 6-12% of all health-care

expenditure.

The Global Burden

Armstrong, Wrobel et al. 2007

Indigenous Australians

In 200405, 6.3% (29,874) of Indigenous Australians had

diabetes, based on self-reports.

Indigenous Australians were 7 times as likely as nonIndigenous Australians to have diabetes recorded on
their death certificate for the period 20032007.
(http://www.aihw.gov.au/diabetes/populations-of-interest/
accessed Dec 2014)

Pre-diabetes: Impaired glucose tolerance and impaired

fasting glucose (cont.)
Progression to diabetes among those with prediabetes is

not inevitable. Studies suggest that weight loss and

increased physical activity among people with prediabetes
prevent or delay diabetes and may return blood glucose
levels to normal.
People with prediabetes are already at increased risk for

other adverse health outcomes such as heart disease and

stroke.

Risk Factors

Pre- diabetes: Impaired glucose tolerance and

impaired fasting glucose

Pre-diabetes is a term used to distinguish people

who are at increased risk of developing diabetes.

People with pre-diabetes have impaired fasting
glucose (IFG) or impaired glucose tolerance (IGT).
Some people may have both IFG and IGT.

The Metabolic Syndrome

(Deadly Quartet)
A cluster of risk factors for diabetes & cardiovascular disease consisting of:

IGT, IFG & Diabetes,

Abdominal obesity
Hypertension

Dyslipidaemia

Obesity
One of the greatest and most serious public health

challenges of the 21st Century. Primary prevention

requires social, economic & cultural changes in all
societies.

Diagnosis of Diabetes Mellitus

Diagnosis

HbA1c

Quiz question

Prevention and Management of DM

Management of DM
The major components of the treatment of diabetes are:

Diet and Exercise

Oral hypoglycaemic
therapy

Insulin Therapy

Diabetes Australia Type 2 diabetes

Prevention Guideline

Summary of Recommendations
Lifestyle modification (Grade A)
Pharmacological interventions (Grade B)
Bariatric surgery (Grade C)
Individuals at high risk of diabetes should be identified through the
use of risk assessment tools (Grade C)
Social marketing (Grade C )
The impact of the built environment on physical activity and food
quality and availability (Grade D)
To be optimally cost-effective and cost saving in the long term,
interventions to prevent diabetes should include/focus on lifestyle
modification
Culturally appropriate lifestyle interventions

(https://www.diabetesaustralia.com.au/PageFiles/763/Primarypreventio
nguideline.pdf accessed Dec2014)

Prevention or delay of diabetes:

Life style modification (diet and exercise)

Self-Care
Patients should be educated to practice self-care.

This allows the patient to assume responsibility and

control of his / her own diabetes management. Selfcare should include:

Blood glucose monitoring

Body weight monitoring
Foot-care
Personal hygiene
Healthy lifestyle/diet or physical activity
Identify targets for control
Stopping smoking

Pharmacological
Management of
Diabetes Mellitus

B. Oral Hypoglycaemic Medications

Types of Insulin

Fast Acting Insulin

Fast acting insulins are clear in appearance. These insulins:

Are very fast acting starting to work from 1 to 20 minutes
Peak approximately one hour later
Last from 3 to 5 hours.
You must eat immediately after injecting one these insulins.
Short Acting Insulin
Short acting insulins are clear in appearance. These insulins:
Begin to lower blood glucose levels within half an hour so you need to have your injection half
an hour before eating
Peak effect at 2 to 4 hours
Last for 6 to 8 hours.
Intermediate Acting Insulin Intermediate acting insulins are cloudy in appearance. They have either protamine or zinc added
to delay their action. These insulins:
Begin to work about 1 1/2 hours after injecting
Peak at 4 to 12 hours
Last for 16 to 24 hours.
Before injecting this type of insulin, check the leaflet inside the pack for instructions on how to
prepare the insulin.
Mixed Insulin
Mixed insulins are cloudy in appearance. They contain pre-mixed combinations of either a fast
acting or a short acting insulin and intermediate acting insulin, making it easier by giving two
types of insulin in one injection. If the insulin is 30/70 then it contains 30% fast acting and 70%
intermediate acting insulin. 50/50 is 50% of each. This insulin can be taken before a meal to
meet the increase in blood glucose levels and provide a stable level of insulin for some hours
after the meal.
Before injecting this type of insulin, check the leaflet inside the pack for instructions on how to
prepare the insulin.
Long Acting Insulin
Long acting insulins are clear in appearance. They typically have no pronounced peak and last
for up to 24 hours.
(http://diabetesaustralia.com.au/Living-with-Diabetes/Type-1-Diabetes/Managing-Type-1-Diabetes/Insulin/#Types of
Insulin, accessed Dec 2014)

C. Insulin

References
National Diabetes Fact Sheet 2003, DEPARTMENT OF HEALTH AND

HUMAN SERVICES Centres for Disease Control and Prevention

World Health Organization. Definition, Diagnosis and Classification of

Diabetes Mellitus and its Complications. Report of WHO. Department of

Non-communicable Disease Surveillance. Geneva 1999
Academy of Medicine. Clinical Practice Guidelines. Management of type 2

diabetes mellitus. MOH/P/PAK/87.04(GU), 2004

NHS. Diabetes - insulin initiation - University Hospitals of Leicester NHS

Trust Working in partnership with PCTs across Leicestershire and Rutland,

May 2008.

Quiz Question

Have a Break

Lecture 2

Complications of Diabetes
1. Acute Complications
2. Chronic complications

Learning Objectives
To learn the pathophysiology, clinical presentation and

management of the acute complications of diabetes due severe

hyporglycemia, and hyper glycaemia (diabetic ketoacidosis and
hyperglycemic hyperosmolar state)
To learn the pathophysiology, clinical presentation and
management of the chronic and complications of diabetes
To appreciate that macrovascular complications are the main
cause of death and the microvascular complications the main
cause of morbidity
To gain an understanding of the mechanisms that lead to
glucose induced cellular damage
To appreciate that prevention of complications is possible
through frequent screening, tight glycaemic control and control
of other risk factors for vascular disease

Acute complications of DM
Hypoglycemia

Hyperglycemic Hyperosmolar State (HHS)

Diabetic Ketoacidosis (DKA)

Signs and symptoms of Hypoglycaemia

Hyperglycaemic Hyperosmolar state

(HHS)
Hyperglycemia

Hyperosmolality and
Dehydration (without Ketosis)

To Recap
Look out for the signs of acute complications.

If you are in a hospital and the patients condition

deteriorates without you being able to determine what it

is:

Met Call 666

Otherwise 000

PATHOPHYSIOLOGY of complications
Several biochemical pathways have been proposed to link
hyperglycemia and microvascular complications:
The Banting Lecture Michael Brownlee - 2005 polyol accumulation
formation of advanced glycation end products (AGEs),
oxidative stress,
activation of protein kinase C (PKC).
These processes are thought to modulate the disease

process through effects on cellular metabolism, signaling,

and growth factors.

General features of hyperglycaemiainduced tissue damage.

Adapted from Brownlee 2005)

Poly/sorbitol Pathway

A key enzyme in this pathway is aldose reductase (AR), which

normally consumes the cellular cofactor NADPH to reduce and
detoxify certain products of metabolic reactions. Through this
process, AR normally converts toxic aldehydes to inactive
alcohols. However, when intracellular glucose levels are high
enough, AR also converts glucose to sorbitol.

Oxidative stress
Glucose metabolism

produces free radicals

Free radicals damage
tissues by disrupting
cell signalling

Nitric Oxide
Nitric oxide is a substance the body naturally produces

which dilates blood vessels, increasing blood flow to the

peripheral vessels and peripheral nerves.
In diabetes, low levels of nitric oxide may lead to
decreased blood flow by constricting the blood vessels
supplying oxygen and nutrients to the nerve, contributing
to nerve damage

Complications of Diabetes Affect Every Part

of the Body
Microvascular Complications
Diabetic Retinopathy
Leading cause of
blindness in
working-age adults
Diabetic Nephropathy
Leading cause of
end-stage renal
disease
Diabetic Neuropathy

Leading cause of
nontraumatic
lower extremity amputations

Macrovascular Complications
Stroke
2- to 4-fold increase in
cardiovascular mortality
and stroke
Heart
Disease

Peripheral
Vascular Disease

Harris MI. Clin Invest Med. 1995;18:231-239.

Nelson RG, et al. Adv Nephrol Necker Hosp. 1995;24:145-156.
World Health Organization. Diabetes Mellitus Fact Sheet 138.2002.

Diabetic Retinopathy
Retinopathy is the most common microvascular complication of

diabetes, resulting in blindness for over 10,000 people with

diabetes per year.
There is evidence that retinopathy begins to develop at least 7
years before the clinical diagnosis of type 2 diabetes
Background retinopathy or non proliferative diabetic retinopathy
(NPDR): increased vascular permeability, venous dilation,
microaneurysms, intraretinal hemorrhage, fluid leakage and
retinal ischemia.
Proliferative diabetic retinopathy (PDR): neovascularization
(which is disordered), vitreous hemorrhage and fibrous
proliferation (scarring).

Harris MI: Undiagnosed NIDDM: clinical and public health issues. Diabetes Care 16: 642
652, 1993

Diabetic Retinopathy

Diabetic Nephropathy
Leading cause of chronic kidney disease

May be asymptomatic for a long time

Can cause a variety of symptoms as it progresses
Predisposed by
Hyperglycemia
Increased blood pressure levels (HTN)
Genetic predisposition
Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR: Development and progression of nephropathy in
type 2 diabetes: the Unite Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int 63:225232, 2003

From Micro to Macro

GFR over 90mls/min is considered normal

Albumin is a protein that is used by the body for normal

cell growth and tissue repair. If the kidneys become

damaged, they may not retain this protein within
bloodstream causing it to be excreted with the urine proteinuria
Microalbuminuria occurs when the kidney leaks small
amounts of albumin into the urine
Macroalbuminuria large amounts of albumin

Pathophysiology
Diabetes causes unique changes in kidney structure.
Classic glomerulosclerosis is characterized by increased

glomerular basement membrane width, diffuse mesangial

sclerosis, hyalinosis, microaneurysm, and hyaline
arteriosclerosis .
Glomerulosclerosis refers to a hardening of the glomerulus in

the kidney. It is a general term to describe scarring of the

kidneys' tiny blood vessels
Tubular and interstitial changes are also present. Areas of

extreme mesangial expansion called Kimmelstiel-Wilson

nodules or nodular mesangial expansion are observed in 40
50% of patients developing proteinuria.

Damaged Kidneys
Hyperglycemia damage to

endothelial cell lining arteries.

Small arteries that supply the

kidneys may become affected

microangiopathy (microvascular)

Localised Ischemia supplying

the cells of kidneys reduces

ability of kidneys

Additionally hyperglycemia can

have direct effects on the kidney

structures leading to an altered
state of function

CKD stages

ESRD
Dialysis

From the kidneys to the heart

Numerous research has shown that microalbuminuria is a

risk factor for CVD.

It has been suggested that microalbuminuria is simply a

marker of generalized atherosclerosis and that this

explains its association with clinical cardiovascular
disease.

Atherschlerosis
Coronary Artery Disease

Peripheral arterial disease

Cerebro-vascular disease
Endothelial Cell Dysfunction

MANAGEMENT OF
DIABETES

Goals
Relieve acute symptoms.

Optimise control of glycaemia and other risk factors

for complications.
Treat existing complications.
Maintain other preventive activities.
http://www.diabetesaustralia.com.au/Documents/DA/What's%20New/12.10.02%20Diabetes%20Management%20in%2
0General%20Practice.pdf accessed Dec 2014

Challenges

The Team Approach

Consider referral to a diabetes educator or dietitian for
consolidation of education.
A podiatrists help needs to be sought if neuropathy,
peripheral vascular disease, foot abnormality or calluses
are present.
Rebates for attendance at private dentists and exercise
professionals are available for patients under the Enhanced
Primary Care Program, as part of a Team Care Arrangement.
Medicare subsidies are available for group education
sessions involving diabetes educators, dietitians and
exercise physiologists.

Some food for thought

Diabetes Care January
2002 vol. 25 no. suppl 1
s28-s32

The Foot in Diabetes

Tutorial Read carefully

Part 2 of the tutorial will be based on this
guideline. The document is posted under
the tutorials section on vUWS along with a
list of names. If your name is on the list
you will need to make a 3 minute
presentation in the tutorial on the topic
listed next to your name (next to which is
the section of the document that covers the
topic). Use the document as a guideline
but dont just read it out. Supplement it
with other research please. If your name is
not up you will be required to present
another week.
http://www.diabetesaustralia.com.au/Page
Files/763/RACP%20Guidelines%20PDF.pd
f