Diabetes Mellitus Flashcards
1
Q
What is the epidemiology of diabetes?
A
- One of the most common endocrine disease affecting all age groups
- Prevalence 6% in UK
- Around 10% of entire NHS budget spent on diabetes - 79% of this spent on complications of diabetes
2
Q
Diabetes is caused by a deficiency or reduced effectiveness of endogenous insulin, resulting in elevated blood glucose.
What are features of T1DM?
A
- Usually adolescent onset but may occur at any age
- Autoimmune destruction of beta cells in pancreas, therefore insulin deficiency
- Symptoms → weight loss, polyuria, polydipsia, DKA
- Associated w/ other autoimmune disorders
3
Q
What are features of T2DM?
A
- Reduced insulin secretion +/- insulin resistance
- Most are >40 yrs
- Can be asymptomatic (often routinely picked up on bloods)
- Symptoms → fatigue, polyuria, polydipsia
- RFs → obesity, lack of exercise, calorie + alcohol XS
4
Q
What are other causes of diabetes mellitus?
A
- Medications → steroids / anti-HIV / new anti-psychotics
- Pancreatic → pancreatitis / surgery / haemochromatosis / cancer
- Endocrine → cushing’s / acromegaly / phaeochromocytoma / hyperthyroid
5
Q
What are methods of checking glucose?
A
- Finger-prick glucose (BM) → quick, easy, bedside
- One-off blood glucose → fasting / non-fasting
- HbA1c
- Oral glucose tolerance test (OGTT)
6
Q
What is HbA1c and when should it not be used?
A
- Glycosylated haemoglobin
- Represents avg blood glucose over last 2-3 months
-
NOT a method for checking glucose in following conditions:
- suspected gestational diabetes
- children
- T1DM
- haemolytic anaemia / haemoglobinopathies
- HIV
- CKD
7
Q
The diagnostic criteria are determined by WHO.
What are the diagnostic results indicating diabetes?
A
- Symptomatic:
- fasting glucose _>_7mmol/L OR
- random glucose _>_11.1 mmol/L (or after 75g OTT)
- Asymptomatic:
- above crtieria on TWO separate occasions
- OR if HbA1c > 48 mmol/L (6.5%) (twice if asymptomatic)
8
Q
What is impaired fasting glucose and impaired glucose tolerance?
A
- Impaired fasting glucose (IFG) → fasting glucose 6.1-7.0 mmol/l
- Impaired glucose tolerance (IGT) → fasting plasma glucose < 7.0 mmol/l and OGTT 2hr value 7.8-11.1 mmol/l
Diabetes UK: Ppl w/ IFG should then be offered OGTT to rule out diabetes diagnosis, a result below 11.1 mmol/l but above 7.8 mmol/l indicates that person doesn’t have diabetes but does have IGT
9
Q
What are the principles of management for diabetes?
A
- Drug therapy to normalise blood glucose levels
- Monitor for and treat complications
- Modify any other risk factors for other conditions eg. cardiovascular disease
10
Q
The long-term management of type 1 diabetics is an important and complex process requiring the input of many different clinical specialties and members of the healthcare team. A diagnosis of type 1 diabetes can still reduce the life expectancy of patients by 13 years and the micro and macrovascular complications are well documented.
What is the management of type 1 diabetes?
A
- Always require insulin to control blood sugar due to absolute deficiency of insulin w/ no pancreatic tissue left to stimulate with drugs
- Different types of insulin available according to duration of action
- HbA1c → monitor every 3-6 months + target < 48 mmol (6.5%)
- Self-monitor BM 4 times/day (before each meal + before bed)
- More frequent monitoring under certain situations
- BM targets → 5-7mmol walking + 4-7mmol before meals at other times
- NICE recommend adding metformin if BMI > 25 kg/m2
11
Q
In which situations is more frequent monitoring recommended for T1 diabetics?
A
If frequency of hypoglycaemic episodes increases, examples:
- during periods of illness
- before, during + after sport
- when planning pregnancy
- during pregnancy and while breastfeeding
12
Q
Insulin therapy revolutionised the management of diabetes mellitus when it was developed in the 1920s. It is still the only available treatment for type 1 diabetes mellitus (T1DM) and is widely used in type 2 diabetes mellitus (T2DM) where oral hypoglycaemic agents fail to gain adequate control.
How can insulin be classified?
A
- By manufacturing process:
- porcine
- human sequence insulin
- analogues
- By duration of action:
- rapid-acting
- short-acting
- intermediate-acting
- long-acting
- premixed preparations
13
Q
Patients often require a mixture of preparations (e.g. both short and long acting) to ensure stable glycaemic control throughout the day.
What are key features of rapid-acting insulin analogues?
A
- Act faster + have shorter duration of action than soluble insulin
- May be used as bolus in ‘basal-bolus’ regimes (rapid/short-acting ‘bolus’ insulin before meals w/ intermediate/long-acitng ‘basal’ insulin once or twice daily)
- Examples: insulin aspart (NovoRapid) and insulin lispro (Humalog)
- Can inject at start of meal, or just after
14
Q
What are key features of short-acting insulins?
A
- Soluble insulin examples → Actrapid (human) and Humulin S (human)
- May be used as bolus dose in ‘basal-bolus’ regimes
15
Q
What are intermediate-acting insulins?
A
- Isophane insulin
- Many pts use isophane insulin in a premixed formulation
16
Q
What are long-acting insulins?
A
- Insulin determir (Levemir) → given once or twice daily
- Insulin glargine (Lantus) → given once daily
17
Q
What are examples of premixed preparations of insulin?
A
- Combine intermediate acting insulin w/ either a rapid-acting insulin analogue or soluble insulin
- Novomix 30 → 30% insulin aspart (rapid), 70% insulin aspart protamine (intermediate)
- Humalog Mix25 → 25% insulin lispro (rapid), 75% insulin lispro protamine (intermediate); Humalog Mix50 → 50% insulin lispro, 50% insulin lispro protamine
- Humulin M3 → biphasic isophane insulin (human) - 30% soluble (short), 70% isophane (intermediate)
- Insuman Comb 15 → biphasic isophane insulin (human) - 30% soluble (short), 70% isophane (intermediate)
18
Q
How is insulin administered?
A
- Vast majority subcutaneously
- Insulin gets broken down by digestive enzymes
- Important to rotate injection sites to prevent lipodysrophy
- Insulin pumps available (‘continues subcut insulin infusions) → deliver continuous basal infusion + prevent patient-activated bolus dose at meal times
- IV insulin for acutely unwell pts (DKA)
- Inhaled insulin available but unused
- Oral insulin analogues in development
19
Q
What is the insulin regimen of choice for all adults?
A
- Multiple daily injection basal-bolus insulin regimens (rather than twice-daily mixed)
- BDS insulin determir (Levemir) is regime of choice; OD insulin glargine or insulin determir is an alternative
- Offer rapid-acting insulin analogues injected before meals, rather than rapid-acting soluble human or animal insulins for mealtime insulin replacement for adults w/ T1DM
20
Q
What constitutes dietary advice for diabetes?
A
- Encourage high fibre, low glycaemic index sources of carbs
- include low-fat dairy products + oily fish
- Control intake of foods containing saturated fats + trans fatty acids
- Limited substitution of sucrose-containing foods for other carbs is allowable, but care should be taken to avoid excess energy intake
- Discourage use of foods marketed specifically at people w/ diabetes
- Initial target weight loss in an overweight person is 5-10%
21
Q
What is the conservative management for diabetes mellitus?
A
- Education about the condition
- Support from specialist diabetic nurse → helps monitor any complications; foot check; blood pressure + urine dip
- Smoking cessation
- Exercise + weight loss
- Diet changes
- Foot-care advice
22
Q
What is the drug management of T2DM?
A
- Majority controlled using oral medication
- First-line → METFORMIN
- Second-line → sulfonylureas, gliptins, pioglitazone
- If oral medication not controlling sugars, then insulin used
23
Q
What are HbA1c targets for T2DM?
A
- Individual targets should be agreed w/ pts to encourage motivation
- Check HbA1c every 3-6 months until stable, then 6 monthly
- NICE encourage relaxing targets for elderly or frail
- Targets depend on treatment/drugs used
It’s worthwhile thinking of the average patient who is taking metformin for T2DM, you can titrate up metformin and encourage lifestyle changes to aim for a HbA1c of 48 mmol/mol (6.5%), but should only add a second drug if the HbA1c rises to 58 mmol/mol (7.5%)
24
Q
Oral hypoglycaemic agents: Metformin
A
- Biguanide
- Increases insulin sensitivity; reduces hepatic gluconeogenesis
- SEs → GI upset, lactic acidosis
- First-line in T2DM
- Cannot be used in pts w/ eGFR < 30
25
Oral hypoglycaemic agents: **Sulfonylureas**
* Examples: **gliclazide**, glimepiride
* Stimulate pancreatic beta cells to secrete insulin
* SEs → **hypoglycaemia**, **weight** **gain**, **hyponatraemia**, SIADH, liver dysfunction
26
Oral hypoglycaemic agents: **Glitazones / Thiazolidinediones**
* Example: **pioglitazone**
* Activate PPAR-gamma receptor in adipocytes to promote adipogenesis + fatty acid uptake
* SEs → **weight** **gain**, **fluid** **retention**, liver dysfunction, fractures
27
Oral hypoglycaemic agents: **DPP4 Inhibitors** **(-gliptins)**
* **Gliptins**
* Increase incretin levels → inhibit glucagon secretion
* Generally well tolerated
* Increased risk of **pancreatitis**
* _Don't_ cause weight gain
28
Oral hypoglycaemic agents: **SGLT-2 Inhibitors (-gliflozins)**
* **Selective sodium-glucose co-transporter-2 inhibitor**
* Examples: canagliflozin, dapagliflozin, empagliflozin
* Inhibits reabsorption of glucose in kidney
* SEs → **UTI**, normoglycaemic ketoacidosis, increase risk of lower limb amputation
* Typically result in weight loss
29
_Other_ hypoglycaemic agents: **GLP-1 agonists (-tides)**
* Incretin mimetic → inhibits glucagon secretion
* **Subcutaneous**
* SEs → **N+V**, **pancreatitis**
* Typically result in weight loss
30
What do you use for **risk** **factor** **modification** in T2DM?
* BP target **\< 140/80** (or 130/80 if end-organ damage) → **ACE-I**
* Pts w/ 10yr CV risk \>10% (QRISK) → **ATORVASTATIN 20mg**
* **T1DM** BP Target = 135/85
ACE-i → renoprotective; black pts offered ACE-i + either thiazide or CCB
31
What messages should be given to all patients with diabetes, if they become **unwell**?
* Inc freq of **BM** monitoring to **4-hrly** or more
* **Fluid** intake → **3L / 24hrs**
* **Sugary** **drinks** if _unable_ to eat
* Ensure box of '**sick day supplies**'
* Access to **mobile** **phone** reduces DKA likelihood
* _Continue_ oral hypoglycaemics if not eating much (exception = metformin if pt dehydrated)
* If pt on **insulin**, _don't_ stop due to risk of **DKA**
32
What is maturity-onset diabetes of the young (**MODY**)?
* **T2DM \< 25 yrs**
* Inherited autosomal dominant condition
* Diff types → **MODY3** (60%), MODY2 (20%), MODY5 (rare)
* **Family hx** of early onset diabetes is often present
* Ketosis is not a feature at presentation
* Pts w/ most common form are v sensitive to **sulfonylureas**
* Insulin not usually necessary
33
What is the **mechanism** of Diabetic Ketoacidosis (**DKA**)?
* Normally body metabolises **carbs** → efficient energy production
* **Ketoacidosis** is alternative pathway in starvation states
* Far less efficient + produces **acetone** as by-product
* In acute DKA → **XS glucose**, but lack of insulin means glucuose not taken up into cells for metabolism, so pushing body into starvation-like state
* **Uncontrolled lipolysis occurs**
* Combination of severe acidosis and hyperglycaemia can be **deadly**
34
Who gets **DKA**?
* May be complication or first presentation of **T1DM**
* Rarely, under extreme stress, T2DMs may develop DKA
* Common precipitating factors → **infection**, **missed** **insulin**, **MI**, surgery, pancreatitis, chemo
35
What is the **clinical** **presentation** of DKA?
* Gradual **drowsiness** + lethargy
* **Abdominal** **pain** + **vomiting**
* Polyuria, polydipsia, **dehydration**
* **Kussmaul** **respiration** (deep hyperventilation)
* Acetone-smelling breath ('pear drops')
36
What is the **diagnostic** **criteria** for DKA?
* **Hyperglycaemic** → BM \> 11 mmol/L
* **Ketonaemia** → \> 3 mmol/L or significant ketonuria (++)
* **Acidaemia** → pH \<7.2
* Bicarbonate \< 15 mmol/l
37
What is the **management** for DKA?
* **_ABCDE_**
* **Fluids** → 1L 0.9% NaCl / 1 hour (if SBP \< 90, give 500ml bolus / 15mins)
* **Insulin** → add 50U human soluble insulin to 50ml 0.9% saline; infuse continuously at 0.1U/kg/hr; ocnt pt's regular long-acting insulin at usual doses + times
* **Monitoring** → check BM + ketones hourly; check VBG at 2h-4h-8h-12h-24h
* **Catheter** → if not passed urine by 1h, aimf or UO 0.5 ml/kg/h; consider NG tube if vomiting/drowsy
* **Avoid** **hypoglycaemia** → if BM \< 14, start 10% glucose at 125ml/h to run alongside saline + prevent hypo
* **K+ replacement**
38
DKA: For fluid therapy, what should you be careful about in **children** & **young** **adults**?
* **_Slower infusion_**
* Higher risk of cerebral oedema
* Often need 1:1 nursing to monitor neuro-observations, headache, irritability, visual disturbance, focal neurology etc.
* Usually occurs **4-12hrs** following commencement of treatment but can present anytime
* If suspicion → **CT** **head** + **snr** **review**
39
What are the guidelines for **potassium** **replacement** in DKA?
* Plasma K+ falls w/ treatment as K+ enters cells
* Do **_NOT_** add K+ to the **1st bag**
* Thereafter, add K+ according to most recent VBG result
40
What are **complications** of DKA and its treatment?
* Gastric stasis
* Thromboembolism
* Arrhythmias 2o to hyperkalaemia/iatrogenic hypokalaemia
* Iatrogenic due to incorrect fluid therapy: cerebral oedema, hypokalaemia, hypoglycaemia
* Acute resp distress syndrome
* Acute kidney injury
