endocrinology - diabetes
TRANSCRIPT
-
8/6/2019 Endocrinology - Diabetes
1/26
Diabetes mellitus
Medicine year 329.09.05
Anne Dawnay
Biochemical Medicine
-
8/6/2019 Endocrinology - Diabetes
2/26
-
8/6/2019 Endocrinology - Diabetes
3/26
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
-
8/6/2019 Endocrinology - Diabetes
4/26
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
-
8/6/2019 Endocrinology - Diabetes
5/26
Why suspect diabetes mellitus?
Secondary eg endocrine disorders,
steroids, pancreatic disease - check for
diabetes
Gestational first occurring during
pregnancy - check especially if high risk
-
8/6/2019 Endocrinology - Diabetes
6/26
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
-
8/6/2019 Endocrinology - Diabetes
7/26
-
8/6/2019 Endocrinology - Diabetes
8/26
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
-
8/6/2019 Endocrinology - Diabetes
9/26
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
-
8/6/2019 Endocrinology - Diabetes
10/26
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
-
8/6/2019 Endocrinology - Diabetes
11/26
Monitoring glycaemic controlDay-to-day
finger-prick blood glucose
urine glucose not recommended
urine ketones for Type 1 as required
-
8/6/2019 Endocrinology - Diabetes
12/26
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
-
8/6/2019 Endocrinology - Diabetes
13/26
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
-
8/6/2019 Endocrinology - Diabetes
14/26
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
-
8/6/2019 Endocrinology - Diabetes
15/26
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
-
8/6/2019 Endocrinology - Diabetes
16/26
CARDS trial1400+ in each of placebo and statin -Colhoun et al 2004 Lancet
-
8/6/2019 Endocrinology - Diabetes
17/26
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
-
8/6/2019 Endocrinology - Diabetes
18/26
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 (
-
8/6/2019 Endocrinology - Diabetes
19/26
Acute diabetic emergencies Hypoglycaemia (plasma glucose
-
8/6/2019 Endocrinology - Diabetes
20/26
DKA - development
Due to insulin deficiency
Commonly drowsy, 10% coma,
hyperventilating, volume deplete and
hypotensive, vomiting, abdominal pain
-
8/6/2019 Endocrinology - Diabetes
21/26
DKA - biochemistry Hyperglycaemia
Ketoacidotic low pH
low bicarbonate
low pCO2
Hyperkalaemic High urea
Often hyponatraemia
-
8/6/2019 Endocrinology - Diabetes
22/26
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
-
8/6/2019 Endocrinology - Diabetes
23/26
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
-
8/6/2019 Endocrinology - Diabetes
24/26
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
-
8/6/2019 Endocrinology - Diabetes
25/26
HONK coma - treatment
Slow reduction in plasma glucose by insulin
infusionRehydrate usually normal saline
Mortality 20-30%
-
8/6/2019 Endocrinology - Diabetes
26/26
The long-term complications ofdiabetes