introduction to diabetes april 2010

7/31/2019 Introduction to Diabetes APRIL 2010

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What should I learn to

understand diabetes How the human body works

What the relationship is betweenblood glucose and insulin

Factors affecting blood glucose levels

Definition of diabetes Diagnosis of diabetes


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Glucose

is an essential source of energy used bythe human body

is stored in the form of glycogen in theliver and the muscles as an energyreserve


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Insulin

After a meal carbohydrates are digested andenter the blood system, which transports themto the cells

is neededfor glucose uptake

and storage

Some cells (those of musclesand fat tissue)need assistance to have blood sugar enter intothem and to be used for energy production

The liverneeds assistance to start the processof storage of glucose in the form of glycogen


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Glucagon

Glucagon is a hormone secreted by thealpha-cells of the pancreas

It is secreted in response to low bloodglucose concentrations

It facilitates glucose release from theglucose store in the liver and inducesproduction of glucose from other sources:gluconeogenesis


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Factors affecting blood

glucose Food (carbohydrate) intake

increases blood glucose

Exercise lowers bloodglucose Stress may increase blood

glucose Alcohol lowers blood

glucose


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Definition of Diabetes

Diabetes is a metabolic disorder of multiple aetiologycharacterised by chronic hyperglycaemia withdisturbances of carbohydrate, fat and proteinmetabolism resulting from defects in insulin secretion,insulin action or both


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Diagnosis of diabetes:symptoms

Frequent and excessive urination Thirst

Hunger Weight loss Tiredness/malaise

Blurred vision


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Some terms in diabetes

: Glucose concentrationmeasured before breakfast after overnight fast

Glucose concentration

measured 1.5 2 hours after a meal Glucose concentration measured at

any time of the day blood test reflecting mean

blood glucose concentrations over the past 8 10weeks


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Diagnosis of diabetes: tests+

mmol/l mg/dlRandom value > 11.0 > 200Fasting value

DiabetesIFG 1 >7.0*>5.6 >126*>1002-hour value(OGTT)

DiabetesIGT2

>11.0>7.8

>200>140

+ Values for venous plasma glucose 1Impaired fasting glycaemia2Impaired glucose tolerance*Repeat and if confirmed = diabetes

Adapted from: A Desktop Guide to Type 2 Diabetes Mellitus,European Diabetes Policy Group 1998-1999


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The importance of glucose

Blood glucose levels are maintainedwithin a narrow range (4 7 mmol/L)

High enough to satisfy the energy needsof cells The nervous system is particularly

dependent on glucose for energy Low enough to minimise the toxic effects

of glucose


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Increases in blood glucose levels

Glucose enters the blood when : Food is digested and absorbed: this is the

main source of glucose

The storage product glycogen is brokendown to glucose (glycogenolysis)

Glucose is synthesised from sources suchas glycerol and amino acids in the liver(gluconeogenesis)


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Decreases in blood glucoselevels

Glucose is removed from the blood to be: Broken down within cells to release energy Converted to glycogen for storage

(glycogenesis)


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Hormonal control inhealth


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Hormonal control of blood glucose:glucagon and adrenaline

Glucagon increases bloodglucose levels by:

increasing glycogenolysisin the liver and skeletalmuscles

increasinggluconeogenesis in theliver

Adrenaline increases

blood glucose levels bystimulating glycogenolysisand lipid breakdown(lipolysis)

Liver

Glycogenbreakdown

Glucosesynthesis

Glycogenbreakdown

Skeletalmuscle

Adipose tissue

Glycogenbreakdown

Lipid (fat)breakdown


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Glycogenbreakdown

Glucosesynthesis

Hormonal control of bloodglucose: insulin

The only hormone to lowerblood glucose levels

Suppresses endogenousglucose production in the

liver inhibits glycogenolysis inhibits gluconeogenesis

Stimulates peripheralglucose uptake in skeletalmuscle and adipose tissue

Glucoseuptake

Liver

Skeletalmuscle

Adipose tissue

Glucoseuptake


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Insulin synthesis and storage Synthesised bypancreatic beta-cells

Series of biochemicalreactions converts theprecursor molecule,preproinsulin, intoinsulin

Insulin is stored ashexamers in secretory

granules beforerelease


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Insulin secretion Insulin is releasedwhen the secretory

granules fuse with thecell membrane(exocytosis)

Hexamers dissociateinto monomers

Monomers aretransported in theblood


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Daily insulin secretion

Time of day

6:000

10

20

30

40

50

60

70

10:00 14:00 18:00

I n s u

l i n ( U / m

L )

Sustained insulin profile

( basal )

Short-lived, rapidlygenerated meal-relatedinsulin peaks ( prandial )

22:00 2:00 6:00

Polonsky et al. J Clin Invest 1988;81:442 8

Breakfast Lunch Dinner


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Biphasic prandial insulinresponse

Each prandial peak has twophases

Phase 1: rapid insulinrelease to suppressendogenous glucose

production in the liver Phase 2: continued releaseas glucose from the mealis absorbed

High insulin levels facilitate peripheral glucose uptake (skeletalmuscle and adipose tissue)

These actions minimise rises in blood glucose associated withmeals


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Diabetes mellitus:type 1


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Type 1 diabetes: reviewPrimary defect:absent or minimal production of insulin

Cause:destruction of pancreatic beta-cells

Symptoms occur when 90% of beta-cells are destroyed


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Characteristics of type 1diabetes

Usually affects people less than 35 yearsof age

Body weight: normal to low Onset: most often in adolescence (10 14

years of age)

Present with classical symptoms Insulin treatment is mandatory


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Insulin treatment is vital

Insulin treatmentshould be initiated assoon as diagnosis is

confirmed Type 1 diabetes was

a fatal disease beforethe discovery ofinsulin

Today insulin savesthe lives of more than

4 million people witht e 1 diabetes


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Honeymoon

Following the acute onset of type 1diabetes, there may be a period(honeymoon phase) of normal or near -normal beta-cell function

However, following this honeymoon phasecomplete beta-cell destruction usuallyoccurs

Consequently, insulin should not bediscontinued during the honeymoon phase


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Relief of hyperglycaemic symptoms

Improvement of quality of life

Prevention and delay of complications

Reduction of mortality

Treatment of accompanying conditions (high blood pressure, high fat

concentrations, etc.)

Diabetes management:objectives


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Aetiology of type 1 diabetes Idiopathic type 1 diabetes

Cause unknown

Autoimmune destruction of beta cells

Thought to be triggered by an environmental agent(e.g. virus) in genetically predisposed individuals

Approximately 90% of type 1 diabetes cases

Onset tends to be fast and aggressive in childrenand adolescents

Slower onset in adulthood is often named late-onset autoimmune diabetes of adults


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Epidemiology of type 1 diabetes

Approximately 10% of all diabetes cases (=25 million)

Incidence peaks in the early teenage years for boysand girls

Geographically: incidence increases considerably from the Equator

to the Poles incidence is highest in Finland and lowest in Japan

Incidence has been increasing over the past 20 years


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Effects of type 1 diabetes onglucose metabolism

In the absence of insulin: The liver continues to produce glucose The uptake of glucose by peripheral tissues is

diminished

Blood glucose levels increase (hyperglycaemia)

Excess glucose is excreted by the kidneys in urine

Increased urination (polyuria) and excessive thirst(polydipsia)


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Effects of type 1 diabetes on lipidmetabolism

In the absence of insulin: Lipolysis in adipose tissue continues and more fatty

acids are released into the blood

The breakdown of fatty acids (ketosis) provides energyfor cells but also ketones (e.g. acetone) as by-products

As ketones build up in the blood, they can be smelt onthe breath, they are excreted by the kidneys in theurine and they increase the acidity of the blood(ketoacidosis)

Diabetic ketoacidosis is a medical emergency


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Effects of type 1 diabetes onprotein metabolism

In the absence of insulin: Protein breakdown is increased and

protein synthesis is decreased

Muscle wasting and weight loss


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Diabetes mellitus:type 2


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Increased hepaticglucose production

Type 2 diabetes: pathophysiologyimpaired insulin secretion +

resistance

Decreased peripheralglucose uptake


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Diabetes Y2003 IDF data

Diabetes Atlas, IDF 2000

Overall prevalence* 5.1% (2-10%)

Type 1 diabetes 5-10% of all cases with diabetesType 2 diabetes 90-95% of all cases with diabetes

*Prevalence = % of all cases in a given population


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First-degree relative withdiabetes mellitus (DM)

Age > 45 years Obesity (BMI > 27 kg/m 2 or

> 20% ideal body weight) Sedentary lifestyle Ethnic predisposition

Hypertension Dyslipidaemia History of gestational

DM (DM in pregnancy) History of delivering a

baby

> 9 lbs Polycystic ovariansyndrome

History of IFG or IGT

Type 2 diabetes: risk factors


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Characteristics of type 2diabetes

Usually affects people >35 years of age Body weight: 80 90% overweight/obese

Onset: most often in the sixties Very often asymptomatic May be diagnosed in relation to already

existing complication


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Type 1 and type 2 diabetes:Similarities

High blood glucose (hyperglycaemia) May have abnormalities in lipids

Develop long-term complications


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Achieving glycaemic controlOptions for treatment of type 2 diabetes: Diet and exercise Sulphonylureas (e.g. Glibenclamide, Glucotrol ,

Amaryl ) Biguanides (e.g. Glucophage ) Alpha glucosidase inhibitors (e.g. Precose ,

Glyset ) Thiazolidinediones (e.g. Actos , Avandia ) Meglitinides (e.g. NovoNorm /Prandin , Starlix )

Insulin or insulin analogues


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Medical management:side effects

Select medication based on drug/patientcharacteristics

OADs:consider action, duration, contraindications,side effects, cost

Insulin:adjust as needed, consider lifestyle changes, hypoglycaemic events


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Epidemiology of type 2 diabetes

Approximately 90% of all diabetes cases(=221 million)

A disorder related to lifestyle, particularly obesity andphysical inactivity

Associated with older age but increasing in children dueto increasing obesity and decreasing physical activity

Incidence:

increasing worldwide

varies among ethnic groups

N l hi i li i


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Natural history: insulin secretionand blood glucose control

IFG, impaired fasting glucose

350 300 250 200 150 100

50

Postprandial glucose

Fasting glucose

Obesity IFG Diabetes Uncontrolled hyperglycaemia

250 200 150

100 50

Insulin resistance

Insulin level

Years of diabetes 10 25 20 15 10 5 0 5 30

Beta-cell failure

G l u c o s e

l e v e

l

( m g /

d L )

R e l a t

i v e

f u n c t

i o n

( % )

Normal

Normal

Adapted from Bergenstal et al. In: Degroot & Jameson (eds). Endocrinology 2001;821 35


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Eff f 2 di b


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Effects of type 2 diabetes onprotein metabolism

Insulin levels are sufficient to preventprotein breakdown and muscle wasting


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Diagnosis

PG, plasma glucose

Random PG 11.1 mmol/L

Random PG 5.5 11.0 mmol/L

Fasting PG 7.0 mmol/L

Fasting PG 5.6 6.9 mmol/L

2-h postchallengePG 11.1 mmol/L

Random PG 11.1 mmol/L

Diabetes

2-h postchallenge

PG 11.1 mmol/L

and/or

Fasting PG7.0 mmol/L

With classicalsigns andsymptoms

Withoutclassical

signs and

symptoms

Data from Watkins et al. Diabetes and its Management. Blackwell Publishing 2003Pickup & Williams. Slide Atlas of Diabetes. Blackwell Publishing 2004


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Metabolic syndrome


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Hyperosmolar non-ketotic coma

(HONK) Hyperglycaemic emergency of type 2 diabetes Usually in older people who have consumed a

large volume of sugary fluid Although insulin levels prevent lipolysis andketogenesis, hyperglycaemia ensues

Patients dehydrated, elderly and frail Treatment: careful rehydration and insulin


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M l li ti f


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Macrovascular complications ofdiabetes

Stroke

Cardiovascular/heart disease

Peripheral vascular disease

International Diabetes Federation. Diabetes Atlas 2006;111 2


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Coronary heart disease (CHD)

Angina, myocardialinfarction (MI), heartfailure

May be confused withhypoglycaemiabecause of a lack ofpain

Immediate and long-term mortalityincreased in diabetes

stenosis

stenosis

Diagram shows stenosis (narrowing) of the coronary arteries

Microvascular complications of


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Microvascular complications ofdiabetes

Retinopathy and blindness

Nephropathy

Neuropathy

Diabetic foot disease

International Diabetes Federation. Diabetes Atlas 2006;111 2


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DCCT: microvascular


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HbA 1c (%)

DCCT: microvascularcomplications increase as HbA 1c

increases

R a t e p e r

1 0 0 p a t

i e n t y e a r s

4

0

12

8

16

0 6 7 8 9 10 11 125

Risk of developingmicroalbuminuria

Risk of retinopathyprogression

R a t e p e r

1 0 0 p a t

i e n t y e a r s

0 6 7 8 9 10 11 12

4

0

12

8

16

5

DCCT. N Engl J Med 1993;329:977 86


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Microangiopathy: definition and

classification Damage to the

microvascularcirculation

Retinopathy(eyes)

Nephropathy(kidneys)

Neuropathy(autonomic andperipheralnerves)


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Hypoglycaemia


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Hypoglycaemia: causes

Insulin treatment and insulinsecretagogues

Taking insulin at the wrong time Wrong insulin doses Inaccurate doses

Missing meals Dietary changes without dose

adjustments

Problems with injection technique or


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Hypoglycaemic symptoms

n Sweating*n Light-headedness*n Trembling/shaking*n Hunger*n Anxiety*n Fast heart raten Lip tinglingn Irritabilityn Pallor

Early signs(mild hypoglycaemia)

n Weak legs*n Drowsiness*n Poor concentration*

n Blurred vision*n Headache*n Confusionn Poor coordinationn Slurred speechn Glazed eyes

n Aggressive behaviourn Seizuresn Loss of consciousness

Late signs (moderate/majorhypoglycaemia)

* Indicate most common

Hypoglycaemia: consequences


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Hypoglycaemia: consequencesRepeatedhypoglycaemicepisodes impair theautonomic

responses tohypoglycaemia

Patients become

unaware ofhypoglycaemia,which increasestheir risk of severe

episodes

Hypoglycaemia

Impaired physiologicalresponses to

hypoglycaemia

Reduced awarenessof hypoglycaemia

Increased vulnerabilityto further episodes of

hypoglycaemia

Hypoglycaemia: unawareness


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yp g yof symptoms

Autonomicsymptomsactivate at alower blood

glucosethreshold thanfor cognitiveimpairment

Patients cannottake preventiveaction

Patients may

1

2

3

4

1

2

3

4

Sweating,tremor

Adrenalinerelease

Sweating,tremor

Adrenalinerelease

Bood glucose (mmol/L)

Hypoglycaemia aware

Hypoglycaemia unaware

Bood glucose (mmol/L)

Start of braindysfunction

Start of braindysfunctionConfusion/lossof concentration

Confusion/lossof concentration

Coma/seizure

Coma/seizure

Permanent brain damage

Permanent brain damage

Treating mild hypoglycaemia


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Treating mild hypoglycaemia

http://www.rcn.org.uk/__data/assets/pdf_file/0009/78606/002254.pdf

First: 10 20 g fast-acting carbohydrate, e.g.:3 6 glucose tablets

90 180 mL fizzy drink or squash (not diet)Two teaspoons of sugar added to a cup of cold drink

50 100 mL energy drink (e.g. Lucozade )

Then:

If next meal is due, add extra carbohydrate

If next meal is not due, eat longer-actingcarbohydrate, such as biscuits or a sandwich

Treating early signs


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Changing the dose:


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Changing the dose:some general rules

Combating hypoglycaemia Reduce insulin dose by at least 20% and

review after 1 week

Preventing hypoglycaemia takes priorityover correcting hyperglycaemia

http://www.rcn.org.uk/__data/assets/pdf_file/0009/78606/002254.pdf

introduction to diabetes april 2010

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