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Year 2 Lab Sci: red = extra conditions - старонка 14


Endocrine


Disorder– core

Diabetes mellitus type 1 (IDDM):

syndrome of chronic hyperglycaemia due to relative insulin

deficiency



Diabetes mellitus type 2 (NIDDM)

:

syndrome of chronic hyperglycaemia due to relative insulin

resistance



How common is it

Affects >120million people worldwide, estimated to affect 370million people by 2030;

Type 1: 16-20% incidence in UK; 2-3% increase/year; highest in N European countries

Type 2: 2-3% prevalence in UK, lifetime risk of 15%; common in all populations

Classification

Primary (idiopathic):

most cases

Secondary (known cause):

1-2% of all cases, but often treatable

Who does it affect

Type 1:

usually juvenile onset but can come on at any age; concordance in identical twins is only 30% = environmental influences must exist but is HLA DR3 and DR4-linked

Type 2:

much more prevalent, possibly due to better longevity and diagnosis; 4 main determinants = increasing age, obesity (↑ risk 80-100x), ethnicity and Fx; higher in Asians, >40yo but teenagers are increasingly being diagnosed with it due to poor diet control/no exercise, M>F; >50% concordance in identical twins = strong genetic component - polygenic; T2DM is associated with central obesity, hypertension, hypertriglyceridaemia, low HDL-cholesterol, modest ↑ in pro-inflammatory markers (ie the metabolic syndrome)

Core symptoms – defined by WHO

Diagnosis:



1. symptoms + one abnormal result

2. no symptoms + two abnormal random results

3. glucose tolerance test (if ?borderline or gestational diabetes)

Fasting plasma glucose > 7.0mmol/L (126mg/dL)

Random plasma glucose > 11.1mmol/L (200mg/dL)

GTT: plasma glucose > 11.1mmol/L

To perform GTT: fast overnight. Measure venous glucose (whole blood values lower). Give 75g of glucose in 300mL water for adult (1.75g glucose/Kg body weight for child) in the morning. Measure venous glucose 2hrs after the drink. >11.1 at 2hrs = DM diagnosis

HbA1C or capillary glucose should not be used to diagnose DM; glycosuria on a urine dipstick may be a normal finding

Impaired fasting glucose: fasting plasma glucose >6.1mmol/L but <7mmol/L = ?lower risk of progression to DM than IGT

Type 1:

weight loss, persistent hyperglycaemia despite diet and medications; presence of autoAB, islet cell AB, anti-glutamic decarboxylase antiAB, ketonuria on urine dipstick

Type 2:

often asymptomatic or will present with micro/macrovascular complications.

Classic triad:

young people present with a 2-6 week history

Weight loss (due to fluid depletion and ↑ breakdown of fat and muscle due to insulin deficiency)

Polyuria (hyperglycaemia causes osmotic diuresis); ketonuria may also be present in young people

Thirst (due to resulting loss of fluids and electrolytes)

Clinical findings:

evidence of weight loss and dehydration, breath may smell of ketones (pear drops), vascular complications inc diabetic retinopathy

Signs

Ketoacidosis; weight loss

Type 1 is associated with other autoimmune conditions

Feature/ symptoms of presentation in a general hospital setting

Complications of DM:




Retinopathy grade



Retinal abnormality (cause)



Action needed



Peripheral retina







Background diabetic/non-proliferative

Dot haemorrhages:

1st sign; development of capillary microaneurysms

Blot haemorrhages:

(leakage of blood into deeper retinal layers (superficial haemorrhages on the ganglion cell layer and outer plexiform layer)

Hard exudates:

exudation of plasma rich in lipids and protein (?old cotton wool spots)

Annual screening

Pre-proliferative

Venous beading/loops:

indicate capillary non-perfusion; beading occurs as the vein passes through an area of ischaemia; venous loops result from closure of the vein at the margin of an area of capillary non-perfusion

Intraretinal microvascular abnormalities:

new blood vessels growing within the retina (healing process), no symptoms evident

Multiple cotton wool spots:

microinfarcts within the retina and the spot itself is made up of axoplasmic debris; debris is removed by macrophage to leave cytoid bodies (little white dots); may be due to HTN (resolve quickly) or DM

Non-urgent referral to ophthalmologist (fluorescein angiography; aggressive control of glucose

Proliferative

New blood vessel formation:

due to widespread capillary non-perfusion (ischaemia). If they grow on the pupil margin and then at the angle of the anterior chamber, they will give rise to ↑ intraocular pressure (thrombotic glaucoma); if capillary growth extends across the macula, then loss of central vision will result

Preretinal or subhyaloid haemorrhage:

preretinal = new blood vessel comes through the retina at the margin of capillary closure – prone to bleed (preetinal haemorrhage = boat-shaped haemorrhage; lies on inferior half of retina)

Vitreous haemorrhage:

further bleeding from a preretinal blood vessel, blood seeps into the vitreous = loss of vision

Urgent referral to ophthalmologist; laser therapy

Advanced

Retinal fibrosis:

ince new vessels have grown, they undergo evolution with collagen tissue growing along the margins of the capillary = fibrotic traction bands;

Traction retinal detachment:

fibrotic traction bands may pull on the retina = ↑ haemorrhage and retinal detachment = loss of vision

Urgent referral to ophthalmologist

Central retina





Maculopathy

Aneurysms ↑ in number and leak = fluid accumulates in the retina; if aneurysms are localised they are associated with fat and protein deposition (circinate retinopathy); oedema extending into the macula = loss of central vision. Final outcome = large exudative plaque in central macular area

Non-urgent referral to ophthalmologist




Diabetic Ketoacidosis:



Biological causes/risk factors

Type 1:

Insulin deficiency due to destruction of pancreatic β-cells (which normally secrete insulin); islet Ag = insulin, glutamic acid decarboxylase (GAD), protein tyrosine phosphatise (IA-2): appear years before clinical presentation

Type 2:

less insulin secretion and insulin resistance due to β-cell dysfunction; ass with obesity, lack of exercise and calorie excess; typically progresses from impaired glucose tolerance or impaired fasting glucose

Psychosocial implications of the disorder

e.g. job, social circumstances, activities of daily living

All pts should be encouraged to live as normal life as possible. Most pts will experience periods of not coping, of helplessness, of denial and acceptance fluctuating over time.

Management

e.g. overall plans, referrals to other services

Type 1: associated with other autoimmune diseases (HLA DR3 and DR4 linked)

Types 2: 25-50% pts already have some form of vascular complications at the time of diagnosis

Overview: genetic predisposition in T2DM, but whether it develops or not is largely lifestyle-dependent; established DM can be reversed by successful diet control + ?bariatric surgery; DM is mostly preventable

Medications and patient education are key to management



Treatment - Psychological

Patient Education:



Improved glycaemic control

; depends on cooperation of pt = depends on understanding of risks of DM and benefits of good glycaemic control (+ keeping lean, stopping smoking, looking after their feet)

Diet:

should be no different than for someone w/o DM

Protein: 1g/Kg bodyweight

Fat: < 35%: avoid processed foods (crisps, chocolate, processed meats)

Carbs: 40-60% intake, slow-burning (low-glycaemic index) best – pasta better than potatoes

Encourage sweetners not sugars (squash, cordials OK), limit fruit juices, cakes, biscuits

Low sugar intake, high fibre, 5 fruit and veg/day, alcohol not forbidden (but be aware it may cause delayed hypoglycaemia), <6g salt/day

Exercise:

any increase to be encouraged; participation in formal exercise programmes is best

Measuring metabolic control of DM:



1. Urine dipstick:

if pt doesn’t perform home blood glucose testing; if dipstick is persistently –ve and there are no symptoms of hypoglycaemia, then assume DM is well controlled.

Problems: urine glucose lags behind blood glucose; mean renal threshold is ~10mmol/L but the range is wide (7-13), and it changes with age; urine tests give no guidance re: blood glucose levels below the renal threshold. Also checks for proteinuria (hence diabetic nephropathy)

2. Home capillary blood glucose testing:

4 samples on 2 days/week note record them in a diary

3. Glycosylated Hb (HbA1C):

glycosylation of Hb is a 2-step process; covalent bond forms between glucose molecule and terminal valine of β-chain of Hb; rate depends on prevailing [glucose] and provides an index of average blood glucose concentration over the lifetime of the Hb molecule = ~6weeks; glycosylated Hb is expressed as a % of total Hb (standardized range 4-6.2%); not good if RBC lifespan is reduced or abnormal Hb or thalassaemia present

4. Glycosyalted proteins (fructosamine):

index of control over last 2-3weeks; glycosylated albumin is the major constituent; useful in pts with anaemia or in pregnancy (when RBC turnover changeable)

Targets:



HbA1C <7.5% to reduce risk of microvascular complications; only some pts will reach targets, and it’ll be harder as DM progresses

Does it matter? YES!



Diabetes Control and Complications Trial: even though 40% pts had blood glucose above non-DM range, there were 60% reduction in progression to retinopathy, nephropathy by 30%, neuropathy by 20% over 7-year period. Risk = hypoglycaemia

Treatment - Biological

e.g. specific drugs

see drug profiles



Medications should be prescribed once lifestyle changes are in place. They will not succeed alone in obtaining good glycaemic control. Tablets will be needed if satisfactory metabolic control is not achieved within 4-6 weeks.

Control CV risks

with ACE-I, a statin, and low-dose aspirin

Type 1:

Pt will always need insulin (short-acting, long-acting, inhaled forms available)

Type 2:

3 main drugs; may need insulin after some time once pancreas destroyed

1. biguanide (metformin)

2. sulfonylureas (tolbutamide, glibenclamide, glipizide, gliclazide, chlopropamide)

3. thiazolidinediones (‘glitazones’)

Others: intestinal enzyme inhibitors, orlistat, rimonbant, gastric banding or bypass surgery (marked obesity unresponsive to 6/12 intensive dieting and graded exercise

Approach to management:



Discuss lifestyle changes and compliance at every stage. As T2DM progresses, β-cell failure will mean glucose control will deteriorate over time requiring pre-emptive and progressive escalation in therapy.

Most pts on tablets will need insulin in time (consider early if HbA1C > 8% or >7% if concurrent CV risks): initially insulin at night

Differential diagnosis

Secondary diabetes:



Drug-induced: corticosteroids, thiazide diuretics, atypical antipsychotics, β-blockers, antiretroviral protease inhibitors

Pancreatic disease: chronic pancreatitis, pancreatectomy (where >90% pancreas has been removed), trauma, pancreatic destruction (hereditary haemochromatosis, CF), carcinoma of the head of panreas

Endocrine: Cushing’s disease, acromegaly, thyrotoxicosis, phaeochromocytoma, glucagonoma

Insulin receptor abnormalities: acanthosis nigricans, congenital lipodystrophy, glycogen storage disease

Genetic syndromes: Friedreich’s ataxia, dystrophia myotonica

Insulin resistance causes: obesity (↑ the rate of release of non-esterified FA causing post-receptor defect’s in insulin’s actions), pregnancy, renal failure, polycystic ovarian syndrome, Asians, acromegaly, CF, Werner’s syndrome, TB drugs, Cushing’s, metabolic syndrome (central obesity, hyperglycaemia, hypertension, dyslipidaemia (high TG, low HDLs)
2010-07-19 18:44 Читать похожую статью
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