Type 1 & Type 2 Diabetes Mellitus Flashcards
What is type 1 diabetes?
Who does it affect?
What is type 1 diabetes associated with?
What is the genetic susceptibility?
What is the environment influence?
Type 1 diabetes : insulin deficiency due to autoimmune destruction of insulin secreting pancreatic beta cells
Onset: common in adolescent but can affect anyone
Assoc. with other autoimmune disease i.e. coeliac’s, Addison’s and pernicious anaemia.
Genetics: >90% people carry HLA DR3 ± DR4
Environment => most type 1 diabetic don’t have close family hx & only 10% with HLA susceptible gene develop diabetes:
=> maternal factors i.e. gestational infections
=> viral infections i.e. coxsackie B
=> exposure to cow’s milk and deficiency of vitamin D
=> childhood obesity
=> psychological stress
What is type 2 diabetes?
Who does it affect?
What is type 2 diabetes associated with?
What is the genetic susceptibility?
Type 2 diabetes = low insulin secretion ± high insulin resistance
Onset: prevalence higher in asians ; men ; >40yrs but teenagers with type 2 increasing
=> pancreatic beta cell function declines with age so incidence of type 2 diabetes increases with age
Assoc. with obesity, lack of exercise, calorie & alcohol excess
Genetics: >80% concordance in twins => higher genetic susceptibility than type 1 diabetes
What are the symptoms of hyperglycaemia?
Polyuria
Polydipsia
Unexplained weight loss
Visual blurring
Genital thrush
Lethargy
What are the other causes of diabetes?
Steroids ; anti-HIV drugs ; newer anti-psychoticss
Pancreatitis ; pancreatic surgery (>90% pancreas removed) ; trauma ; pancreatic destruction (haemachromatosis, cystic fibrosis) ; pancreatic cancer
Cushing’s disease ; acromegaly ; phaeochromocytoma ; hyperthyroidism ; pregnancy
How do you diagnose diabetes?
i) Symptoms of hyperglycaemia AND raised venous glucose once : Fasting >7mmol/L or Random >11.1mmol/L
OR
ii) Raised venous glucose on 2 separate occasions : Fasting >7mmol/L or Random >11.1mmol/L or glucose tolerance test (OGTT) - 2h value >11.1mmol/L
OR
iii) HbA1c >48mmol/mol => Avoid in pregnancy, children, type 1 DM & haemoglobinopathies
What are the features of type 1 diabetes?
Weight loss
Persistent hyperglycaemia despite diet & medications
Presence of autoantibodies i.e. islet cell antibodies and anti-glutamic acid decarboxylase antibodies
Ketonuria
Differences between type 1 and type 2 diabetes:
Type 1 DM: => Starts before puberty => HLA D3 & D4 linked => Autoimmune beta-cell destruction => Polydipsia, polyuria, weight loss, ketosis
Type 2 DM: => Older patients (usually) => No HLA assoc. => Insulin resistance / beta cells dysfunction => Asymptomatic / complications e.g. MI
*Not all new onset diabetes in older patients = Type 2 DM
=> If ketotic ± poor response to oral hypoglycaemic
=> Patient slim ± has family or self Hx of autoimmunity
=> Could be latent autoimmune diabetes in adults (LADA)
=> Measure islet cell antibodies
What is the best diet for an obese patient with type 2 diabetes?
Dietary carbohydrates = big determinant of post-prandial glucose levels & low carbohydrate diets improve glycemic control
=> low carb ketongenic diet better at maintaining/lowering blood glucose than low glycemic/reduced calorie diet
What preventative measures are taken before starting medications for diabetes?
Education and lifestyle choices
- Exercise to increase insulin sensitivity
- Healthy diet (less saturated fats, sugars, more starch carbs, moderate protein)
- Negotiate HbA1c and review 3-6 monthly
- Assess vascular risk: control BP, initiate high intensity atorvastatin if needed
- Foot care
- Advice to not drive if hypoglycaemic spells - inform DVLA
* Bariatric surgery may be a cure for T2DM in selective patients
How do you manage type 2 diabetes?
Lifestyle modification - diet, exercise, weight control => always consider first and then alongside meds
- Monotherapy: Metformin - 1st line therapy
- If HbA1c >58mmol/mol, start dual therapy
=> Metformin + DPP4 inhibitor e.g. sitagliptin
=> Metformin + pioglitazone
=> Metformin + sulphonylurea (SU)
=> Metformin + SGLT-2i e.g. glifazon - If HbA1c still >58mmol/mol, start triple therapy
=> Metformin + DPP4 inhibitor + SU
=> Metformin + pioglitazone + SU
=> Metformin + SU/pioglitazone + SGLT-2i
If triple therapy doesn’t work, try:
=> Metformin + SU + GLP 1 mimetic
=> Insulin based therapy
What class of drug is metformin?
What is its mechanism of action?
What are its side effects?
Biguanide => works by increasing insulin sensitivity & helps weight
Side effect: nausea, diarrhoea (try modified release version), abdominal pain
=> does not cause not hypoglycaemia
=> avoid if eGFR <36ml/min - risk of lactic acidosis
What are DPP4 inhibitors?
What is its mechanism of action?
DPP4 inhibitors (aka gliptins) e.g. sitagliptin block the action of DPP4
=> DPP4 is an enzyme which destroys the hormone incretin
=> Incretins decrease blood glucose levels => released after eating and augment secretion of insulin
What are Glitazone?
What is its mechanism of action?
What are its side effects?
Glitazone increases insulin sensitivity
Side effects: hypoglycaemia, fractures, fluid retention, raised liver function test (do LFT every 8wks for 1 year)
Contraindications: past/present congestive cardiac failure, osteoporosis => monitor weight & stop if weight increasing or oedema
What are sulphonylurea?
What is its mechanism of action?
What are its side effects?
Sulphonylurea increases insulin secretion e.g. gliclazide 40mg/d
Side effects: hypoglycaemia (monitor glucose) ; weight increase
What are SGLTI?
What is its mechanism of action?
What are its side effects?
Selective sodium-glucose co-transporter-2 inhibitor => blocks reabsorption of glucose in the kidneys and promotes excretion of excess glucose in the urine
How do you treat type 1 diabetes?
Lifelong insulin therapy
Blood glucose monitoring
Eating healthy food ; maintaining weight ; exercising; maintaining blood sugar
What are the 4 different types of insulin available?
How is it administered?
Short-acting (regular) insulin
Rapid-acting insulin
Intermediate-acting (NPH) insulin
Long-acting insulin
=> administered via subcutaneous injection not orally because insulin gets digested by gastric enzymes
How do you assess risk in diabetes?
BP control => crucial for preventing macrovascular diseases and mortality
Smoking cessation
Plasma lipids
How do you control BP in type 1 and type 2 diabetes?
Type 1 DM:
=> Treat BP if >135/85mmHg
=> If albuminuria or two or more features of metabolic syndrome then treat 130/80mmHg
=> ACEi (1st line) or ARB
Type 2 DM:
=> Target BP if <140/90mmHg
OR
=> Target BP <130/80mmHg if kidney, eye or CVS damage
=> ACEi (1st line)
=> African / caribbean give ACEi + diuretic or calcium channel blocker
What are the macrovascular complications of diabetes?
How can we prevent these complications?
- MI 4x more common
- Stroke 2x more common
=> women at higher risk because diabetes removes protection from oestrogen
Prevention : Address risk factors i.e. diet, smoking, hypertension
=> Smoking cessation
=> Control BP
=> Statin e.g. atorvastatin 20mg even if no overt IHD, vascular disease, microalbuminuria
=> Aspirin 75mg reduces vascular complications (secondary prevention)
Good control of hyperglycaemia is key to prevent microvascular complications in diabetes.
What are the microvascular complications of diabetes?
Retinopathy - microalbuminuria
Nephropathy
Neuropathy - loss of sensation in a ‘glove & stocking’ distribution => infections => ischaemia => gangrene => amputation
*For details pg 210-212 ox handbook
What is the emergency state in uncontrolled type 1 diabetes?
Diabetic ketoacidosis
=> Ketoacidosis: alternative metabolic pathway used in starvation ; less efficient ; produces acetone = sweet pear drop smell
=> Diabetes: excess glucose due to lack of insulin - cannot be taken up into cells - starvation like state => diabetic ketoacidosis
=> Gradual drowsiness, vomiting,
Good control of hyperglycaemia is key to prevent microvascular complications in diabetes.
What are the microvascular complications of diabetes?
Retinopathy
Nephropathy
Neuropathy
*For details pg 210-212 ox handbook
What happens in diabetic nephropathy?
What do the investigations show?
Hyperglycaemia => diabetic nephropathy (albuminuria + glomerulonephropathy) => CKD => End stage kidney disease
Investigations:
Microalbuminuria => urine dipstick -ve for protein but urine albumin:creatinine ratio >3mg/mmol => renal disease + high vascular risk
=> ACEi or ARB to protect kidneys
Diabetic neuropathy:
Amputations are common but preventable in diabetes.
What happens in diabetic neuropathy?
Neuropathy : Loss of sensation in a ‘glove & stocking’ distribution
=> caused by loss of pain sensation leading to increased mechanical stress & repeated joint injury
=> swelling, instability, deformity
=> sensory loss is patchy, absent ankle jerks, neuropathy deformity i.e. charcot joint
Diabetic neuropathy:
When do you suspect ischaemia?
How do you investigate ischaemia?
Foot pulses cannot be felt
=> doppler pressure measurement
=> neuropathy or vascular disease increases risk of ulceration
=> educate patients to daily inspect feet
=> remove calluses regularly as haemorrhages & tissue necrosis can hide under
Diabetic neuropathy:
What are the characteristics of a foot ulcer in diabetes?
Painless, punched out ulcer in an area of thick callus ± infection
What is the emergency state in uncontrolled type 1 diabetes?
What are the assoc. symptoms?
Diabetic ketoacidosis
=> Ketoacidosis: alternative metabolic pathway used in starvation ; less efficient ; produces acetone = sweet pear drop smell
=> Diabetes: excess glucose due to lack of insulin - cannot be taken up into cells - starvation like state => diabetic ketoacidosis
=> Gradual drowsiness, vomiting, dehydration
*check glucose in everyone presenting with unexplained vomiting, abdominal pain, polyuria, polydipsia, lethargy, anorexia, ketotic breath
How do you diagnose diabetic ketoacidosis?
Acidaemia : pH <7.3
Hyperglycaemia >11mmol/L
Ketoaemia or significant ketonuria
How do you manage diabetic ketoacidosis?
=> 1L 0.9% saline fluid over 1h
=> Venous blood gas for pH, bicarbinate ; bedside and lab glucose & ketones, U&E’s, FBC, CRP, CXR, ECG
=> 0.1 unit/kg/h insulin continuously
=> Continue patients long-acting insulin at usual dose & time
=> Aim for a fall in ketones of 0.5mmol/L/h
=> Check capillary blood glucose hourly
=> Glucose <14mmol/L start 10% glucose alongside saline to prevent hypoglycaemia
=> Add K+ replacement from 2nd bag fluid onwards (insulin drives K+ in cell)
