Diabetes Mellitus Flashcards
What is the pathophysiology of Type 1 Diabetes Mellitus?
- T1DM develops as a result of autoimmune pancreatic beta-cell destruction in genetically susceptible indivisuals.
- Inflammation of Beta cells proceeds for months to years without clinical feature
- Leads to ultimate beta cell destruction
- 80-90% of beta cells have been destroyed – hyperglycaemia develops
- Insulin resistance has no role in the pathophysiology of type 1 diabetes
What is the incidence of T1DM?
T1 DM can present at any age - highest incidence is in children aged 10- 14 years
What is the clinical presentation of T1DM seen in children? (5)
- -Hyperglycaemia (random plasma glucose >11.1)
- Polyuria
- Polydipsia
- Weightloss
- Excessive tiredness
What is the clinical presentation of T1DM seen in adults?
- Ketosis
- Rapid weight loss
- BMI < 25
- Age < 50
- Personal and/or family of autoimmune
How is T1DM diagnosed in children?
- Fasting plasma glucose : > 7.0 mmol
- 2 hour plasma glucose : >11.1 mmol
- HBA1C > 48
How is T1DM diagnosed in adults?
Clinical diagnosis – if patient presents with hyperglycaemia
* Typically with 1 or more of : ketosis, rapid weight loss, age < 50 years, BMI < 25, personal or family hx of autoimmune disease
How often should HBA1C be measured in adults and children
Children : every 3 months
Adults : every 6 months
What is the first line management of T1DM?
- Basal bolus insulin
Long acting insulin (basal dose) + rapid acting insulin (bolus dose)
What are the main complications associated with Diabetes mellitus? (5)
- DKA
- Hypoglycaemia
- Retinopathy
- Peripheral/Autonomic neuropathy
- Cardiovascular disease ( MI or Stroke)
What is the most common microvascular complication of diabetes?
Retinopathy
- asymptomatic until later stage
- Risk is increased with high HBA1C
What are the signs of Diabetic Retinopathy which may be seen? (4)
develop microaneurysms, exudates, haemorrhages and glaucoma
What is the most common cause of endstage renal disease in the world?
Diabetic kidney disease
What is the earliest sign of Diabetic Kidney disease?
Uriary albumin excretion >30mg/day is the earliest signs of disease
What regular monitoring is indicated in Diabetes mellitus? (5)
- Check for Coeliac disease at diagnosis
- HBA1C
- 3 months for children
- Every 6 months for adults - Thyroid disease
- At diagnosis
- Anually - Eye health
- Children have opticial r/v every 2 years
- Annual eye screen for retinopathy from age 12 > - BP, CVS risk factors} Anually
- Screening for ‘Diabetic foot disease’ } anually
- Ischaemia (pulses) and Neuropathy (sensation)
When are ACEinhibitors/ARBs indicated in Diabetes? (2)
BP >135/85 or >130/80 with >2 features of metabolic syndrome
Insulin resistance, impaired glucose tolerance, abdominal obesity, reduced high-density lipoprotein (HDL)-cholesterol levels, elevated triglycerides, and hypertension.
When are statins indicated in diabetes?
(3)
- T1 DM without CVS disease
* 1. >40 years or have had diabetes for > 10 years
* 1. >Evidence of nephropathy or CVD factors
What is the pathophysiology of Type 2 Diabetes? (2)
- defined by deficit in insulin secretion and increased insulin resistance that leads to high glucose levels in the blood
- Insulin reistance is aggravated by ageing, being overweight and obesity.
What are the risk factors of T2DM? (5)
Obesity
Certain ethnic groups – black, south asain
Family hx of T2 DM
Hx of gestational diabetes
PCOS
What are the clinical features associated with Type 2 Diabetes Mellitus? (7)
- Polydipsia, Polyuria, Polyphagia
- Unintentional weight loss – if marked hyperglycaemia is present
- Candida infections
- Skin infection – cellulitis, abscesses
- UTI – cystitis, pyelonephritis
- Fatigue- early signs of progressive CVS disease
- Blurred vision – due to elevated glucose
What investigations aid the diagnosis of diabetes mellitus? (4)
- Fasting plasma glucose > 7 mmol/L
-
HBA1C > 48 mmol
Reflects degree of hyperglycaemia over the preceding 3 months - 2 hour post-load glucose after 75g oral glucose
> 11.1 mmol/L - Random plasma glucose
> 11.1 mmol/L
What are the blood pressure targets for T2DM?
Aim for BP < 135/85
What is the first line management of BP?
1st line :
Ace inhibitor / ARB
What is the 2nd line management of BP?
2nd line : + CCB or thiazide like diuretic
Ace inhibitor + CCB/Thiazide like diuretic
What is the third line management of BP?
Ace inhibitor + CCB + Thiazide like diuretic
What is the indication for asprin 75mg in T2DM?
Indication :** T2DM + Cardiovascular disease**
How is Type 2 Diabetes mellitus diagnosed : Symptomatic patient? (2)
- Fasting glucose greater than or equal to 7.0 mmol/l
- Random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
How is Type 2 Diabetes mellitus diagnosed : Asymptomatic patient? (3)
**Criteria below must apply **and be demonstrated on 2x seperate occasions
1. Fasting glucose greater than or equal to 7.0 mmol/l
1. Random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
What is the HBA1C required for the diagnosis of HBA1C?
a HbA1c of greater than or equal to 48 mmol/mol (6.5%) is diagnostic of diabetes mellitus
What does the HBA1C value indicate in the diagnosis of Diabetes Mellitus? (2)
- HbA1c of greater than or equal to 48 mmol/mol (6.5%) is diagnostic of diabetes mellitus IF Patient is symptomatic
- If not symptomatic, must be repeated
- HbAlc value of less than 48 mmol/mol (6.5%) does not exclude diabetes
In which conditions may HBA1C not be used for diagnosis? (8)
- haemoglobinopathies
- haemolytic anaemia
- untreated iron deficiency anaemia
- suspected gestational diabetes
- children
- HIV
- chronic kidney disease
- people taking medication that may cause hyperglycaemia (for example corticosteroids)
Which values indicate ‘Prediabetes’ in T2DM? (2)
HBA1C : 42 - 47
Fasting glucose : 6.1 - 6.9
Which values indicate T2DM? (2)
Fasting glucose > 7 mmol/L
HbA1C > 48
What is the definition of impaired fasting glucose?
A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l
What is the management of patient found to have** impaired fasting glucose**? (2)
Offer an oral glucose tolerance test to r/o diabetes
- > 11.1 } patient has T2DM
- If 7.8 - 11.1 } indicates patient has impaired glucose tolerance
What is the second line management of T2DM?
- Metformin
Target : < HBA1C 48mmol
- Increase from 500mg BD to TDS if HBA1C target not being met
How are GI SE: managed when patient is on Metformin?
modified-release metformin should be trialled
Why may target HBA1C rise to 53 mmol in patients with T2DM? (2)
- If patient is on a hypoglycaemia causing drug e.g. Sulphonylureas
- Already on one drug, but HbA1c has risen to 58 mmol/mol (7.5%)
When is second line drug therapy indicated in T2DM?
If the HbA1c has risen to 58 mmol/mol (7.5%) then further treatment is indicated
What is the mechanism of action of Metformin? (4)
- acts by activation of the AMP-activated protein kinase (AMPK)
- increases insulin sensitivity
- decreases hepatic gluconeogenesis
- may also reduce gastrointestinal absorption of carbohydrates
What are the side effects to metformin? (3)
- Gastrointestinal upsets are common (nausea, anorexia, diarrhoea), intolerable in 20%
- Reduced vitamin B12 absorption - rarely a clinical problem
- Lactic acidosis with severe liver disease or renal failure
What are the contraindication to metformin therapy? (4)
- Chronic kidney disease:
* R/v dose if creatinine > 130 or eGFR<30 - Lactic acidosis if taken following tissue hypoxia e.g Sepsis, recent MI, AKI
- Iodine contraining contrast media e.g. Coronary angiography
* can increase risk of contrast nephropathy - Metformin should be stopped on the day and 48 hours after procedure
What is the management if metformin is contraindicated in T2DM? (2)
- if the patient has a risk of CVD, established CVD or chronic heart failure:
* SGLT-2 monotherapy - If no risk of above
* DPP4 inhibitor or pioglitazone or a sulfonylureas
When should SGLT-2 inhibitors be added alongside metformin in the first line management of T2DM?
- What should be done prior to adding SGLT2 inhibitors?
(4)
- the patient has a high risk of developing cardiovascular disease (CVD, e.g. QRISK ≥ 10%)
- the patient has established CVD
- the patient has chronic heart failure
* Can also be added at any point if patient develops any of the above later on* - Metformin should be established and titrated up before intriducing the SGLT-2 inhibitor
What is the MOA of action of : DPP4 inhibitors
- Give examples
- (4)
- Inhibit enzyme DPP4 when prevents GLP-1 from being activated
- Increase in GLP-1 concentration
- Higher GLP } stimulates insulin and inhibits glucoagon secretion
Stinagliptin, Linagliptin
What are the side effects of DPP4 inhibitors? (1)
Pancreatitis
What is the mechanism of action of Pioglitazone? (3)
- Agonist of PPAR-gamma receptor on surface of adipose tissue, skeletal muscles and liver
- Activation of receptor increases transciption of insulin responsive genes and gluconeogenesis
- Increases cellular sensitivity to insulin and inhibits gluconeogenesis
What are the side effects of Pioglitazone? (4)
- Fluid retention - thus worsening heart failure, acts of distal renal tubules to increase N+ and water absorption
- Weight gain - increase in water weight
- Liver dysfunction
- Fractures - increases bone marrow adiposity (undifferentiated bone cells) and decreased osteoblast activity
What is the MOA of action of : SGLT-2 inhibitors (3)
- Give examples
MOA
* SGLT2 channels are found in proximal tubule and mediate reabsorption of 90% of glucose in urine
* SGLT-2 inhibitors block these channels and promote renal excretion of glucose
Examples : Canagliflozin, Dapgliflozin
What are the side effects of SGLT-2 inhibitors? (2)
UTI/yeast infections
Flu like sx
What is the MOA of action of : Sulfonylureas? (2)
MOA -
* bind to ATP-dependant K+ channel on the cell membrane of pancreatic beta cells and increase pancreatic insulin secretion
* therefore are only effective if functional B cells are present
Gliclazide, Glimiparide
What are the side effects of Sulfonylureas inhibitors? (4)
- Hypoglycaemic episodes
- Icreased appetite and weight gain
- SIADH
- Liver dysfunction
What is the mechanism of action of insulin? (3)
- Insulin acts on receptors and causes cells, muscles and all tissue to take up glucose from the blood
- Inhibits glycogenolysis, gluconeogenesis, lipolysis
- Increases glycogenogenseis, fatty acid synthesis, and cellular potassium uptake
What is the second line drug therapy in T2DM? (4)
Dual therapy - add one of the following:
* metformin + DPP-4 inhibitor
* metformin + pioglitazone
* metformin + sulfonylurea
* metformin + SGLT-2 inhibitor (if NICE criteria met)
What is the third line drug therapy in T2DM? (3)
If a patient does not achieve control on dual therapy then the following options are possible:
- metformin + DPP-4 inhibitor + sulfonylurea
- metformin + pioglitazone + sulfonylurea
- metformin + (pioglitazone or sulfonylurea or DPP-4 inhibitor) + SGLT-2
- if certain NICE criteria are met
insulin-based treatment
What is the further management if triple therapy is not effective? (2)
- GLP-1 mimetic - switch one of the three drugs to this // continue metformin
- Insulin
What is the mechnism of action and examples of GLP-1 mimetic? (2)
GLP-1 analogues increase incretin which help the body produce more insulin and reduce hyperglycaemia
Delivered as an injectable pen device
e.g. Exenatide, Liraglutide
What is the criteria for initiating GLP-1 mimetic? (2)
- BMI ≥ 35 kg/m² or medical problem assoc with obesity
- BMI < 35 and insulin therapy would not be sutiable due to occupational risks/weight loss still benefits
What is the criteria for continuing GLP-1 mimetic therapy once initiated? (2)
- reduction of at least 11 mmol/mol [1.0%] in HbA1c
and - a weight loss of at least 3% of initial body weight in 6 months
How is insulin therapy started in T2DM? (2)
- Indicated for further management when triple therapy does not control BMs
- Continue metformin but review other drugs
- Start with intermediate acting insulin } Human NPH insulin
When is 20mg of Atorvastatin indicated in Diabetes Mellitus? (2)
Primary prevention
* QRISK > 10%
* Type 1 diabtes mellitus
When is 80mg of Atorvastatin indicated? (3)
- Known Ischaemic heart disease
- Cerebrovascular disease
- Peripheral arterial disease
What is the cause of Diabetic foot disease?(2)
- neuropathy: resulting in loss of protective sensation (e.g. not noticing a stone in the shoe), Charcot’s arthropathy, dry skin
- peripheral arterial disease: diabetes is a risk factor for both macro and microvascular ischaemia
What is the clinical presentation of diabetic foot disease? (2)
- neuropathy: loss of sensation
- Ischaemia: absent foot pulses, reduced ankle-brachial pressure index (ABPI), intermittent claudication
What are the complications of Diabetic foot disease? (5)
complications:
calluses, ulceration,
Charcot’s arthropathy : neuropathy resulting in deformity of the foot and ankle as unable to sense weight distribution/trauma
cellulitis, osteomyelitis, gangrene
How does peripheral neurophathy present in Diabetes mellitus? (3)
- Leads to sensory loss and not motor loss
- Glove and stocking’ distribution - with the lower legs affected first due to the length of the sensory neurons supplying this area.
- Diabetic neuropathy may be painful
What is the medical management of neuropathic pain? (6)
-
- First-line treatment: (alternate between drugs if one does not work)
* amitriptyline
* duloxetine
* gabapentin
* pregabalin - Rescue therapy for exacerbations : Tramadol
- Localised neuropathic pain : Topical capaicin
What is the defintion of ‘Gastrointestinal autonomic neuropathy’
Damage to autonomic nerves involves in regulating the GI system secondary to prolonged chronic hyperglycaemia
What are the clinical features of gastrointestinal autonomic neuropathy? (3)
- Gastroparesis : delayed gastric emptying
* Sx : bloating and vomiting
* management options include ;
metoclopramide, domperidone or erythromycin (prokinetic agents) - Chronic diarrhoea
often occurs at night - Gastro-oesophageal reflux disease
caused by decreased lower esophageal sphincter (LES) pressure
- What is the meaning of Insulin analogs?
- “insulin” analogs are analogs that have been designed to mimic the body’s natural pattern of insulin release
- they have minor structural or amino acid changes that give them special desirable characteristics when injected under the skin.
*Name two insulin analogs?
- Rapid acting insulin analogs - Apart, Lispro
- Long acting insulin analogs - Insulin Detemir (Levermir) and Insulin galargline (Lantus)
What is the meaning of Human insulin?
Synthetic human insulin is identical in structure to your own natural insulin
Name two human insulins? (2)
- Regular human insulin - a form of fast acting injected insulin
- NPH insulin - intermediate acting human insulin
What are the issues associated with human insulin compared to analogs?
- Delayed onset of action
- Variable peak and duration of action
This leads to reduced control of blood sugar levels - may cause high or low blood sugar levels
*What is the definition and use of ‘Fast acting insulin’?
Is absorbed quickly from your fat tissue (subcutaneous) into the bloodstream.
Use : control the blood sugar during meals and snacks and to correct high blood sugars
*What are the two types of ‘fast acting insulin’?
- Rapid acting injected insulin analog
- Regular human insulin
*What is the mechanism of action of Rapid acting injected insulin?
- Injected 5 - 10 minutes before eating
- Peak action : 2 hours
- Duration of action : 4 hours (to fade completely)
*What is the mechanism of action of Regular Human Insulin?
- onset of action : 1/2 hour to 1 hour
- peak effect : 2 to 4 hours,
- duration of action : 6 to 8 hours.
The larger the dose of regular the faster the onset of action, but the longer the time to peak effect and the longer the duration of the effect.
*What is the indication of intermediate acting insulin?
- absorbed more slowly, and lasts longer
- used to control the blood sugar overnight, while fasting and between meals
Name two examples of intermediate acting insulin
- NPH Human insulin
- Premixed insulin - NPH premixed with regular human insulin or rapid acting analg
Profile of action : combination of short and intermediate acting insulins
What is the mechanism of action of intermediate acting insulin?
- Onset of action : 1-2 hours
- Peak action : 5 hours
- Duration : 12 hours
What is the formulation of premixed insulin? (2)
NPH (intermediate acting, Human insulin) is mixed with either;
- Rapid acting insulin analogs
e.g. NPH + lyspro or NPH + Aspart
or
- Fast acting human regular insulin
What is the benefit and disadvantage of using premixed insulin?
**Benefit **
* -: no mixing of insulin is necessary
* - Only one injection
Disadvantage
* NPH has unpredictable mode of action and no alternative long acting insulin is sutible
* When dose is increased : both long and short acting insulin doses will be increased thus increasing the risk of hyper and hypo glycaemia
Why can’t premixed insulin be mixed with other long acting insulins? (2)
- insulin glargine (Lantus®) and detemir (Levemir®) cannot be mixed in the same syringe with other insulins
- Affects their mechanism of action and changes how they work as they are made for slow + gradual release in the blood
*What is the indication and function of long acting insulin analogs?
- They provide relatively constant insulin levels that plateau for many hours after injection without any peaking
- Is absorbed slowly
- Lasts most the day
- Use : controls the blood sugar overnight, while fasting and between meals
- The long acting insulin analogs are suitable for background or basal insulin replacement.
*What is the mechanism of action of long acting injected insulin analogs?
onset of action within 60-90 minutes,
Peak action: around 5 hours
Duration of action -
12-24 hours. : Determir
24 hours : Glargine
*Name two main types of long acting insulins and their regimens?
- Insulin detemir (Levemir®)
Detemir is usually injected twice a day. - Insulin glargine (Lantus®)
Glargine is usually injected once daily, but may be given twice daily if needed.
*Explain what Background /Basal insulin does?
- Controls glucose overnight and between meals by keeping fat in fat tissue and curbing glucose production from the liver.
- Provides a low, continuous level of insulin
Can be;
* Long-acting insulin, which you inject once or twice daily
e.g. insulin analogs, insulin glargine, insulin detemir and NPH.
Or
* Can be a rapid-acting insulin continuously infused under the skin via an insulin pump.
*Explain what Background Bolus insulin does?
Provides extra insulin following meal times / high blood sugar to retun the glucose level back to target
- Rapid acting insulin analogues such as Insulin aspart
What is the insulin regime of choice in Type 1 diabetes mellitus?
- Basal bolus insulin regime
- Basal dose
Twice daily insulin detemir
- Bolus dose
Rapid acting insulin analogie
When should metformin be considered as an adjunct to insulin therapy in T1DM?
BMI of 25 kg/m2 or above (23 kg/m2 or above for people from South Asian backgrounds
AND
they want to improve their blood glucose control while minimising their effective insulin dose.
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