endocrinology - diabetes

8/6/2019 Endocrinology - Diabetes

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Diabetes mellitus

Medicine year 329.09.05

Anne Dawnay

Biochemical Medicine


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Glycaemic control

oblood glucose

Insulin release from pancreas

Stimulation of tissue uptake

of glucose, decrease in

hepatic glucose production

Blood glucose decreases hence insulin

release no longer stimulated


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Why suspect diabetes mellitus?

Type 1 absolute insulin deficiency short

history, usually younger, lethargy, weight loss,

polyuria, polydipsia

Type 2 relative insulin deficiency due to

insulin resistanceusually older, insidious onset,

often overweight, may be lethargy/weight

loss/polyuria/polydipsia (mild cf Type 1), may

present with deteriorating

eyesight/hypertension


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Why suspect diabetes mellitus?

Secondary eg endocrine disorders,

steroids, pancreatic disease - check for

diabetes

Gestational first occurring during

pregnancy - check especially if high risk


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What are the consequences of

diabetes mellitus?

Short term poor glycaemic control leading to fluid

and electrolyte abnormalities see later

Longer term microvascular and macrovascularcomplications

Type 1 after 20y retinopathy 75%, severe 50%

nephropathy 25%

Type 2 - 40% some retinopathy at diagnosissingle commonest cause of ESRF

BPprevalence 80%

CV risk = non-DM with previous MI

NB On average, adult type 2 is twice age of adult type 1


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Diagnostic algorithm for diabetes mellitusvenous plasma glucose

Random glucoseDiabetes highly

unlikely

Symptomatic *

Fasting

glucose

Diabetes

excluded

Impaired fasting

glycaemia

OGTT

Impaired glucose toleranceLifestyle advice, check in 1 year

Diabetes

>11.0

>7.0

5.6-11.0

3 days

WHO in UK 1.6.2000


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Do not ignore IFG or IGT !High risk of developing type 2 DM

OGTT in non-diabetic adults age 45-64,n= 2593, follow-up 10y

82.1% normal 2.0% (1/50) developed DM

4.0% IFG4.6% (1/22) developed DM

12.4% IGT 10.8% (1/9) developed DM 1.5% both IFG and IGT 49.9% (1/2) developed DM

Diab Med 2003;20:1027-1033


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Do not ignore IFG or IGT !Development of type 2 DM can be prevented

Placebo vs lifestyle (weight loss + activity)

vs metforminn=3234 adults with IFG+ IGT, follow-up 2.8y

Lifestyle reduced incidence of type 2 by 58%

Metformin reduced incidence of type 2 by 31%

NEJM 2002;346:393-403


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Monitoring glycaemic controlDay-to-day

finger-prick blood glucose

urine glucose not recommended

urine ketones for Type 1 as required


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Monitoring glycaemic controlLonger term - HbA1c

Glucose + amino groupsp glycated protein

Amount glycated depends on glucose concentrationand time of exposure non-enzymatic

Hb glycated with glucose is HbA1c

Red cell life-span 120 days

Amount HbA1c proportional to time averageglucose concentration over preceding 4-6 weeks

Normal 4-6% - aim for


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Limitations of HbA1c

Patients with abnormal haemoglobins (egthalassaemias, sickle cell) - interfere withquantitation of the fraction that is glycated

Patients with abnormal red cell lifespan eghaemolytic anaemia, uraemia shorter lifespanmeans less glycated so falsely low estimate ofglycation

Alternative fructosamine = glycated serumprotein = mainly albumin, half-life 20 days soreflects shorter term control than HbA1c

NB HbA1c CANNOT be used to diagnose diabetes


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Poor glycaemic control increases

microvascular complications

DCCT Type 1 (NEJM 1993;329:977-986 etc)

UKPDS Type 2 (Lancet 1998;352:837-853 and854-865, BMJ 1998;317:703-712 and 713-720 etc)

Both trials show decreased development and progression of

retinopathy, nephropathy and neuropathy with improvedglycaemic controlBUT increased incidence ofhypoglycaemia

Showed some benefit on macrovascular but not significant -?not long enough follow-up


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Hyperlipidaemia Common in all patients with diabetes

Increased cardiovascular risk (cf general

population) - type 2 have same risk as non-diabetic with previous MI

Lifestyle/glycaemic control/statins/fibrates

Recent CARDs trial (Lancet 21.08.04) shows

dramatic benefit of atorvastatin (10 mg/d) inprimary prevention of CV disease and death inType 2 diabetes with normal LDL cholesteroland at least one complication - ?treat allregardless


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CARDS trial1400+ in each of placebo and statin -Colhoun et al 2004 Lancet


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Microalbuminuria The uria is micro not the albumin

Above normal but urine protein dipstick negative

Develops in c.30% of patients (type 1 and 2) by 10-15y

Early warning of high risk of developing clinicalproteinuria (dipstick positive) that heralds onset ofdiabetic nephropathy - also high regression, especiallychildren!

Microalbuminuria also predicts total mortality andcardiovascular mortality and morbidity [2-fold rel. risk]

Strict control of hypertension mandatory toprevent/slow progression of DN and CV risk


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Microalbuminuria - definitions Varies from lab to lab Overnight lower than daytime

Compliance can always get clinic sample

Can use:

timed samples excretion rate eg 20-200Qg/min (


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Acute diabetic emergencies Hypoglycaemia (plasma glucose


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DKA - development

Due to insulin deficiency

Commonly drowsy, 10% coma,

hyperventilating, volume deplete and

hypotensive, vomiting, abdominal pain


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DKA - biochemistry Hyperglycaemia

Ketoacidotic low pH

low bicarbonate

low pCO2

Hyperkalaemic High urea

Often hyponatraemia


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DKA - treatment

rehydrate normal saline

i.v. insulin monitor glucosei.v. potassium monitor frequently

rarely bicarbonate

Note for paediatric patients there are

separate national guidelines


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HONK coma - development Severe hyperglycaemia due to

inadequate treatment/excess glucose

intake/further impairment of insulin

sensitivity

Hyperglycaemia causes volume depletion

due to osmotic diuresis and high plasmaosmolality causes cerebral dehydration

and thence stupor/coma


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HONK coma - biochemistry Hypernatraemia with volume depletion

Elevated urea

Not acidotic normal bicarbonate, pH, pCO2

Normokalaemic

Hyperosmolar (glucose, urea, sodium) Always check paracetamol, salicylate, ?alcohol

in comatose patient


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HONK coma - treatment

Slow reduction in plasma glucose by insulin

infusionRehydrate usually normal saline

Mortality 20-30%


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The long-term complications ofdiabetes

endocrinology - diabetes

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