Diabetes I and II Flashcards
What is type I diabetes?
AI, idiopathic absolute insulin deficiency secondary to beta cell destruction.
How may DM be diagnosed?
- Symptoms + RBG >11.1mmol/L
- FPG > 7.0 mmol/L
- HbA1C >48 mmol/mol (6.5%)
- OGTT @2h >11.1 mmol/L
Range of impaired fasting glucose?
FPG 6.1 - 6.9 mmol/L
(Normal =
Does TIIDM have a genetic component?
Yes:
- MZ twin concordance up to 80%
- 4/10 offspring and 1/3 siblings develop IGT or DM
- Polygenic; >250 genes
How to distinuighs between TIDM and TIIDM?
- C-peptide (endogenous insulin production)
- Anti-GAD and anti-islet cell Abs (TIDM)
What are the principles of TIIDM Mx?
- LoW / diet & exercise
- Oral hypoglycaemics
- Self BSL monitoring
- Regular surveillance microvascular complications
- Risk reduction macrovascular complications (BP, lipids, smoking)
Principles of dietary management in DM?
- Refer dietician
- Weight loss (most cases)
- Low GI carbs
- Reduce sat fats
Role of exercise in Mx DM?
- Increases glucose uptake into muscle
- Improved sensitisation can last 2-3/7
- May transiently increase (stress hormone); usually overall decrease in BSL
Self BSL targets in DM monitoring?
Fasting: 6-8mmol/L
2h post prandial: 6-10mmol/L
What determines HbA1C levels?
HbA1C is proportional to average BSL over previous 1-3 months.
Prognosis pre-diabetes (impaired glucose tolerance)?
- 1-5% / year develop diabetes
- 50-80% revert to normal
Diagnostic criteria impaired glucose tolerance?
-FBG 6.1-6.9mmol/L
OGTT 2h: 7.8 - 11.0 mmol/L
What is TIIDM?
Syndrome of disordered metabolism and inappropriate hyperglycaemia secondary to absolute / relative deficiency of insulin, or a reduction in biological effectiveness of insulin or both.
What are the macrovascular complications of diabetes?
- Ischeamic Heart Disease
- Peripheral Vascular Disease
- Cerebrovascular Disease
What are the microvascular complications of diabetes?
- Retinopathy
- Neuropathy
- Nephropathy
What is the risk of developing diabetic complications related to?
- Duration of diabetes
- DM Control (e.g. HbA1C)
- BP control
- Control of CV RFx (lipids, smoking)
- Genetic susceptibility
How is diabetic eye disease classified?
- Non proliferative
- Pre-proliferative
- Proliferative
What other eye conditions are more common in diabetics?
- Cataracts
- Glaucoma
What is microalbuminura?
Albumin excretion rate 30-300mg / 24h.
Screening test for diabetic neuropathy?
Albumin creatinine ratio:
N =
Progression of untreated microalbuminura (type I and II)?
TIDM: albuminuria increases at 10-20% / year to over neprophathy in 10-15y.
TIIDM: 20-40% progress to overt nephropathy
What is macroproteinuria?
Albumin excretion rate >300mg / 24h
Natural history untreated macroproteinuria? (TI and TII)
- TI: ESRF 50% at 10y, 75% at 20y
- TII: 20% ESRF at 20y
What are the most common types of neuropathy in diabetes?
- Distal symmetric polyneuropathy (glove and stocking)
- Autonomic
How does diabetes relate to other macrovascular risk factors?
Diabetes is a macrovascular RFx in itself BUT other macro RFx also more likely in diabetics (i.e. increased HTN, dyslipidemia etc)
Which areas are prone to ischaemia in DM patients with PVD?
-Great toe
-Medial surface 1st metatarsal head
-Lateral surface 5th metatarsal head
Secondary infection common
Why is exertion dsypnoea important to investigate in DM patients?
Myocardial ischaemia often silent; need high degree of clinical suspicion.
Prevention and treatment of diabetic retinopathy?
- Regular examination (asymptomatic until visual loss occurs)
- Laser treatment
- Meticulous BSL control
- Smoking cessation
- ?RAAS blockade
Treatment of diabetic nephropathy?
- Strict BP control (ACE, ARB)
- Strict BSL control (HbA1C
Treatment of diabetic neuropathy?
- Control BSLs
- TCAs
- SNRI antidepressants
- Anti epileptics
- Opioid analgesics (e.g. tramadol)
- Capsaicin cream
How should foot ulcers be prevented in high risk feet?
- Foot care education
- Daily inspection
- Podiatry r/vs
- Early treatment skin injury
- Good footwear
- Callus detection and treatment
- Urea cream for dry feet
- Early referral for ulcers
What are the lipid targets for high risk patients?
- LDL: 1.0 mmol/L
- TGs:
Features suggestive of LADA cf TIIDM?
- Lean build
- Anti islet Abs
- Rapid progression to insulin
Where are the highest rates of TIDM?
Finland and other Northern European countries
Which genes predispose to most genetic risk of TIDM?
HLA genes on Chr 6: highly polymorphic and modulate immune defence of body.
HIGH RISK = HLA:
-DR3 -DQ2
-DR4 -DQ8
Distinction between TIDM and TIIDM?
Key distinguishing feature (T1 v TII) is presence of auto-Abs against B-cell auto-ags:
- IAA: insulin reaction
- GADA: glutamic acid decarboxylase —> catalyses formation of gaba-aminobutyrate; located in B cells
- IA2A: insulinoma associated auto antigen 2 —> islet antigen 2, membrane bound in B cells
- ZnT8A: zinc transporters.
- C peptide
What are the four major determinants of TIIDM?
- Age
- Obesity
- Ethnicity
- FHx
Outline the inheritance component of TIIDM?
identical twins of DMII patients >50% chance of developing diabetes; siblings = 25%.Polygenic disorder: many susceptibilities e.g. TCF7-L2, KCNQ1.
Environmental factors predisposing to TIIDM development?
Low weight at birth and 12 months associated with glucose intolerance later in life. Poor early nutrition thought to impair B-cell development.
What is insulin resistance?
Failure of target tissue to respond normally to insulin (liver, muscle, adipose tissue major tissues in glucose regulation).
What does insulin resistance lead to?
- Failure to inhibit endogenous glucose production (gluconeogenesis) in liver.
- Failure of glucose uptake and glycogen synthesis in skeletal muscle following a meal.
- Failure to inhibit lipoprotein lipase in adipose tissue, leading to excess circulating FFAs.
Subacute presentation of DM?
SUBACUTE: clinical onset several months or years, esp older patients.
-Polydipsia
-Polyuria
-LoW
PLUS
-lack of energy
-visual blurring (owing to glucose induced changes in refraction)
-pruritus vulvae or balanaitis due to Candida infection
What is acanthosis ingrains?
Indicative of severe insulin resistance: blackish pigmentation of back of neck and axillae.
Outline pathophysiology of DKA.
- Occurs due to lack of insulin (first presentation, lack of compliance to insulin medication).
- Unrestricted hepatic glucose production —> hyperglycaemia —> osmotic diuresis —> dehydration and electrolyte disruption —> decreased Na+ (water shift to ECF).
- Fat mobilisation —> increased FFA —> ketoacids —> metabolic acidosis
- Severe hyperglycemia exceeds renal threshold for glucose and ketone resorption —> glucosuria and ketonuria.
- Total body depletion of K+, but serum K+ may be normal or elevated following a secondary shift from ICF to ECF due to lack of insulin —> increased plasma osmolality.
- Total body PO34- depletion
Ketoacidosis precipitating factors?
- New onset TIDM
- Inadequate / inappropriate insulin therapy
- EtOH abuse
- Infection
- Pancreatitis
- Drugs: corticosteroids and thiazides
Principles of ketoacidosis management?
1) Rehydration
2) Identify K+ level; correct imbalance (potassium)
3) Correct hyperglycemia: Insulin therapy
4) Identify precipitant
Fluids to be used in mx DKA?
-1L N saline over 30min - 2h
Change to 5% dextrose when glucose
Principles of potassium treatment in Mx DKA?
Aim K+ 3.5 - 5mM:
1) K+ 5mM: withhold K+ but monitor levels
Insulin in Mx DKA?
-IM: 0.1 IU/kg/h
-IV infusion: 6-8 units hourly via pump THEN ADJUST to BSLs
Continue infusion until acidosis resolved then switch to s/c insulin (basal bolus).
How is effective osmolality determined?
2 (Na+) + glucose
What is hyperglycaemia hyperosmolar state?
AKA hyperosmolar nonketotic coma:
- severe hyperglycemia
- minimal ketosis
- profound dehydration
- depressed sensorium / coma
- efective osmolality >330 Osm/kg
Mx hyperglycemia hyperosmolar state?
- Fluids: 2L hypotonic saline (0.45%) over 1-2h
- Monitor urine output and CVP if indicated
- Insulin
- Potassium
- Prophylactic heparin
- identify cause
Broad pathogenesis of hyperosmolar state?
Relative lack of insulin –> hyperglycaemia –> glycosuria –> polyuria –> volume depletion –> renal insufficiency –> hyperosmolarity –> fluid shift from neutrons to ECF –> mental obtundation and coma.
Mx of hypoglycaemia?
- If possible: sugary fluids
- Unconscious / risk of aspiration:
- -> IV dextrose 50% (25-50mL)
- -> IM/SC glucagon 1mg
- Administer long acting carb
- Recheck glucose 20-30 min later
What may precipitate HHS?
-Sepsis / stroke / MI / CHF / renal failure / dialysis / recent surgery / burns
Why is dehydration more severe in HHS than DKA?
- More gradual onset =Increased duration of metabolic decompensation
- impaired fluid intake
What are the precipitants of DKA/
8Is precipitating DKA:
i) Infection
ii) Ischaemia / infarction
iii) Iatrogenic (glucocorticoids)
iv) Intoxication
v) Insulin missed
vi) Initial presentation
vii) Intra abdominal process
viii) Intra op / peri op stress
Pathophysiology of diabetic nephropathy?
- thickening of capillary BM and glomerular mesangium resulting in glomerulosclerosis and renal insufficiency
- diffuse glomerulosclerosis more common than nodular inter capillary glomerulosclerosis (Kimmelsteil- Wilson lesions)
Clinical features of peripheral neuropathy?
- Paresthesias (tingling, burning)
- Bilateral, symmetric
- Decreased perception of vibration / pain / temp
- Decreased ankle reflex
Clinical features in motor neuropathy of DM?
- Less common than sensory neuropathy
- Delayed motor nerve conduction w/ muscle weakness/ atrophy
- May involve one nerve trunk or more (mono neuritis complex)
- Diabetic amyotrophy
what is diabetic amyotrophy?
Pain, weakness, wasting of hip flexors or extensors
Clinical features of diabetic autonomic neuropathy?
- Postural hTN
- Tachycardia
- Decreased CV response to valsalva
- Gastroparesis / alternating diarrhoea constipation
- Urinary retention
- Erectile dysfunction
What is diabetic dermopathy?
Atrophic brown spots commonly in pretitibial region known as “shin spots”.
Secondary to increased glycosylation of tissue proteins or vasculopathy.
Dermatologic manifestations of DM?
- Diabetic dermopathy
- Eruptive xanthomas
- Necrobiosis lipidoica diabeticorum
What is necrobiosis lipidoica diabeticorum?
Rare complication characterised by thinning skin over the shins allowing visualisation of subcutaneous vessels.
Bone and joint manifestations of DM complication?
- Juvenile cheiroarthropathy
- Dupuytyren’s contracture
- Bone demineralisation
- Frozen shoulder
Clinical features of hypoglycemia?
- Whipple’s Triad:
i) Serum glucose
What are symptoms of neuroglycopenia?
- Dizziness
- Headache
- Clouding of vision
- Mental dullness
- Fatigue
- Confusion
- Seizures / Coma
What are the common causes of hypoglycaemia due to hyperinsulinism?
- Exogenous insulin
- Sulphonylurea reaction
- AI hypoglycemia
- Pentamidine
- Insulinoma
What are the common causes of hypoglycaemia without hyperinsulinism?
- Severe hepatic dysfunction
- Chronic renal insufficiency
- Hypocortisolism
- EtOH
- non-pancreatic tumours
- inborn error of carb metabolism, glycogen storage deficiency
How is insulin infusion made up in DKA and Mx (i.e. rate and ongoing Mx)?
- 50units of insulin made up to 50mLs with 0.9%NSal ==> 1UN/mL.
- Rate of 0.1unit/kg/h up to 6 units / h.
- When glucose
Insulin in HHS?
-Initial dose insulin 0.05UN/kg (max 3 Units)
-Reduce insulin infusion when glucose 18mmol/L
Infuse 0.45% (half NS) at 250mL/h
