Diabetes

Question 1

What is type 1 diabetes?

Answer 1

Autoimmune disorder where the insulin-producing beta cells of the islets of Langerhans in the pancreas are destroyed.

This results in an absolute deficiency of insulin resulting in raised glucose levels

Patients tend to develop T1DM in childhood/early adult life and typically present unwell, possibly in diabetic ketoacidosis

Question 2

What are the symptoms of T1DM?

Answer 2

Weight loss
=> Polydipsia
=> Polyuria
=> Dehydration

May present with diabetic ketoacidosis:
=> abdominal pain
=> vomiting
=> reduced consciousness level
=> Kussmaul respiration (deep hyperventilation)
=> Acetone-smelling breath (pear drop smell)

Question 3

What is type 2 diabetes?

What are the symptoms?

Answer 3

This is the most common cause of diabetes in the developed world.

=> caused by a relative deficiency of insulin due to an excess of adipose tissue. In simple terms there isn’t enough insulin to ‘go around’ all the excess fatty tissue, leading to blood glucose creeping up.

Symptoms:
Often picked up incidentally on routine blood tests
Polydipsia
Polyuria

Question 4

How is T1DM investigated and diagnosed?

Answer 4

Investigations:
1. Urine dip for glucose and ketones

2. Fasting glucose & random glucose (see below for diagnostic thresholds)
3. HbA1c is not as useful for patients with a possible or suspected diagnosis of T1DM as it may not accurately reflect a recent rapid rise in serum glucose
4. C-peptide levels are typically low in patients with T1DM
5. Diabetes-specific autoantibodies are useful to distinguish between type 1 and type 2 diabetes
   => Anti-GAD (antibodies to glutamic acid and decarboxylase) - present in ~80% with T1Dm
   => Islet cell antibodies - present in 70-80%
   => Insulin autoantibodies (IAA) - present in 90% of young children and 60% of older children

Question 5

What is the diagnosis criteria for T1DM?

Answer 5

Diagnostic criteria for T1DM:

1. Fasting glucose greater than or equal to 7.0mmol/l
2. Random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
   * if the patient is asymptomatic then the above criteria must be demonstrated on two separate

NICE suggests:
Diagnose type 1 diabetes on clinical grounds in adults presenting with hyperglycaemia, where people with type 1 diabetes typically (but not always) have one or more of:
=> ketosis
=> rapid weight loss
=> age of onset below 50 years
=> BMI below 25 kg/m²
=> personal and/or family history of autoimmune disease

Consider further investigation in adults that involves measurement of C‑peptide and/or diabetes‑specific autoantibody titres if:
type 1 diabetes is suspected but the clinical presentation includes atypical features e.g. > age 50 years, BMI of 25 kg/m² or above, slow evolution of hyperglycaemia or long prodrome

Question 6

How is type 2 diabetes investigated?

Answer 6

The diagnosis of type 2 diabetes mellitus can be made by either a plasma glucose or a HbA1c sample.

If the patient is symptomatic:
i) Fasting glucose greater than or equal to 7.0 mmol/l

ii) Random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
iii) HbA1c >48mmol/l
* if patient is asymptomatic, then above criteria must be demonstrated on two separate occasions

Question 7

What is impaired glucose tolerance (pre-diabetes T2)?

Answer 7

A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)

Impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l

‘People with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn’t have diabetes but does have IGT.’

1. Fasting glucose 6.1-6.9mmol/l
2. HbA1c 42-47 mmol/l
   * <41mmol = normal HbA1c

Question 8

In which conditions can HbA1c not be used for diagnosis?

Answer 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)

Question 9

How is T1DM managed?

Answer 9

1. HbA1c
   => monitored every 3-6 months

=> adult target of HbA1c level of 48 mmol/mol (6.5%) or lower.

• NICE recommends taking into account factors such as the person’s daily activities, aspirations, likelihood of complications, comorbidities, occupation and history of hypoglycaemia
  2. Self-monitoring of blood glucose

=> recommend testing at least 4 times a day, including before each meal and before bed

=> more frequent monitoring is recommended if frequency of hypoglycaemic episodes increases; during periods of illness; before, during and after sport; when planning pregnancy, during pregnancy and while breastfeeding

3. Blood glucose targets
   => 5-7 mmol/l on waking and
   => 4-7 mmol/l before meals at other times of the day
4. Type of insulin
   i) Offer multiple daily injection basal–bolus insulin regimens, rather than twice‑daily mixed insulin regimens, as the insulin injection regimen of choice for all adults

ii) Twice‑daily insulin detemir is the regime of choice.
* Once-daily insulin glargine or insulin detemir is an alternative

iii) Offer rapid‑acting insulin analogues injected before meals, for mealtime insulin replacement for adults with type 1 diabetes

5. Metformin
   NICE recommend considering adding metformin if the BMI >= 25 kg/m²

Question 10

T2DM management:

Dietary advice

Answer 10

High fibre, low glycaemic index sources of carbohydrates

Low-fat dairy products and oily fish

Control intake of foods containing saturated fats and trans fatty acids

Limited substitution of sucrose-containing foods for other carbohydrates is allowable, but care should be taken to avoid excess energy intake

Discourage the use of foods marketed specifically at people with diabetes

Initial target weight loss in an overweight person is 5-10%

Question 11

T2DM management: HbA1c targets

Answer 11

Individual targets should be agreed with patients to encourage motivation

HbA1c should be checked every 3-6 months until stable, then 6 monthly

2015 the guidelines changed so HbA1c targets are now dependent on treatment/management:

1. Lifestyle only => 48mmol/mol
2. Lifestyle + metformin => 48mmol/mol
3. Includes any drugs which may cause hypoglycaemia e.g. lifestyle + sulfonylurea => 53mmol/mol
4. Already on one drug but HbA1c has risen to 58mmol/mol => 53mmol/mol

NICE: 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%)

Question 12

What is the drug treatment for T2DM?

Answer 12

Patients who tolerate metformin:

1. Metformin is still first-line and should be offered if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions

2. If HbA1c rises to 58 mmol/mol (7.5%) then a second drug should be added:
=> sulfonylurea
=> gliptin
=> pioglitazone
=> SGLT-2 inhibitor

3. If despite the above, HbA1c rises to, or remains above 58 mmol/mol (7.5%) then triple therapy should be offered:
   => metformin + sulfonylurea + gliptin
   => metformin + sulfonylurea + pioglitazone
   => metformin + sulfonylurea + SGLT-2 inhibitor
   => metformin + pioglitazone + SGLT-2 inhibitor
   OR
   => insulin therapy should be considered

*If triple therapy is not effective, not tolerated or contraindicated AND BMI > 35
=> metformin + sulfonylurea + GLP-1 mimetic

Patient’s who do not tolerate metformin:

1. if the HbA1c rises to 48 mmol/mol (6.5%) on lifestyle interventions:
   => sulfonylurea
   => gliptin
   => pioglitazone
2. If the HbA1c has risen to 58 mmol/mol (7.5%) then one of the following combinations should be used:
   => gliptin + pioglitazone
   => gliptin + sulfonylurea
   => pioglitazone + sulfonylurea
3. If despite the above, HbA1c rises to, or remains above 58 mmol/mol (7.5%) then consider insulin therapy

Question 13

What is the criteria for GLP-1 mimetic e.g. exenatide?

1. If triple therapy not effective, tolerated or contraindicated
   AND
   BMI >35

Then consider combination therapy with metformin, sulfonyluria and glucagon-like peptide1 (GLP1) mimetic

*only continue if there is a 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

Answer 13

INFO CARD

Question 14

Hypertension in Diabetes:

1. T2DM BP targets are the same as for patients without type 2 diabetes

i) Age <80 years
=> Clinic BP: 140/90mmHg
=> ABPM / HBPM: 135/85mmHg

ii) Age >80 years
=> Clinic BP: 150/90 mmHg
=> ABPM / HBPM: 145/85mmHg

2. T1DM BP targets
   i) If no albuminuria or features of metabolic syndrome, the threshold for starting anti-hypertensives >135/85mmHg
   ii) If albuminuria present or >2 features of metabolic syndrome, then threshold for starting anti-hypertensives = 130/80 mmHg
3. ACE inhibitors or angiotensin II receptor blockers (ARB) are first-line
   an ARB is preferred if the patient has a black African or African–Caribbean family origin

Answer 14

INFO CARD

Question 15

Diabetes significantly increases risk of CVD:

Answer 15

Following the 2014 NICE lipid modification guidelines

1. T1DM who do not have established CVD:

i) Offer statin treatment with atorvastatin 20 mg for the primary prevention of CVD if the person:
=> Is older than 40 years of age, or
=> Has had diabetes for more than 10 years, or
=> Has established nephropathy, or
=> Has other CVD risk factors i.e. obesity and hypertension

ii) For all other adults with type 1 diabetes, consider statin treatment with atorvastatin 20 mg for the primary prevention of CVD.

iii) T1DM who have established CVD:
Advise statin treatment with atorvastatin 80 mg for secondary prevention of CVD.

2. T2Dm does not have established CVD, offer atorvastatin 20 mg once daily for primary prevention of CVD if:
   => aged 84 years and younger, and their estimated 10-year risk of developing CVD is 10% or more.
   => 85 years of age or older, taking into account the person’s preferences, benefits and risks of treatment, and co-morbidities (including frailty and multimorbidity).
   => The person has a diagnosis CKD

ii) T2DM has established CVD, offer atorvastatin 80 mg once daily for secondary prevention of CVD.
iii) Aim for a greater than 40% reduction in non-HDL cholesterol.

Question 16

What are the potential complications of diabetes?

Answer 16

1. Macrovascular complications (damage to large blood vessels):
   => atherosclerotic CVD i.e. stroke, MI, peripheral artery disease (PAD = risk factor for diabetic foot ulcers)
2. Microvascular complications (damage to small blood vessels):

=> Nephropathy - albuminuria, hypertension, renal atheroma or ischaemia. Diabetes is the commonest cause of CKD and end-stage renal disease

=> Retinopathy

=> Peripheral neuropathy - distal, symmetrical polyneuropathy. Painful neuropathy may cause symptoms of numbness, burning or shooting pain, tingling / paraesthesia of hands ± feet in a stocking and glove distribution, often at night. Can progress to persistent neuropathic pain

3. Metabolic:
   => DKA - triad of hyperglycaemia, metabolic acidosis and ketonaemia. Life-threatening emergency that can lead to dehydration and electrolyte imbalance, MI, shock, aspiration pneumonia (more common in type 1)

=> Hypoglycaemia - adverse effect of insulin. Blood sugar <3.5mmol/L. Can result in convulsions, inability to swallow, loss of consciousness, coma if severe

=> Hyperosmolar hyperglycaemic state (HHS) - rate but life-threatening emergency in type 2. Develop severe hyperglycaemia, over several weeks, due to acute illness and dehydration. May present with frequency, thirst, nausea, confusion and severe dehydration

=> Dyslipidaemia - commonly assoc. with T2DM => increases risk of CVD

4. Psychological = depression & anxiety, distress / phobia of needles
5. Infections and other skin complications
   => people with diabetes prone to infections especially UTI and skin - if severe can lead to amputations
6. Reduced quality of life with managing hypo/hyperglycaemia states, daily admin of insulin, regular self-monitoring and need to plan daily activities i.e. eating and exercise (T1DM)
7. Reduced life expectancy
   => T1DM - reduces life expectancy by 11-15 years
   => T2DM by 10 years

Question 17

How is diabetes monitored for complications?

Answer 17

1. At every review appt:
=> measure HbA1c 
=> measure BMI, waist circumference 
=> assess depression, anxiety, eating disorders (inc. intentional insulin omission to lose weight)
=> check smoking status
=> monitor neuropathy 

2. Once a year:
=> check injection sites
=> assess CVD risk factors i.e. smoking, waist circumference, blood glucose control, BP, gull lipid profile and family hx of CVD 
=> eye/kidney/ foot disease screening 
=> thyroid disease screening 

*be alert for possibility of development of other autoimmune disease i.e. coeliacs, addisons, B12/folate deficiency

3. Eye disease screening
   => within 3 months of diagnosis
   => annual screen
4. Diabetic kidney disease
   => First urine sample of the day once a year (early morning urine) - check for albumin:creatinine ratio and eGFR
   => diagnose CKD if eGFR <60mL or ACR >3mg/mmol
   => ACE-i + maintain sBP <130/80 mmHg
5. Diabetic Neuropathy
   => offer men to discuss erectile dysfunction + PDE-5 inhibitor sildenafil
6. Foot problem
   => screen annually / sooner if problems arise

Question 18

Insulin therapy (admin subcutaneously):

1. Rapid-acting insulin analogues
=> act faster and have a shorter duration of action than soluble insulin 
- onset: 5 mins 
- peak: 1 hour
- duration: 3-5 hours

=> may be used as the bolus dose in ‘basal-bolus’ regimes (rapid/short-acting ‘bolus’ insulin before meals with intermediate/long-acting ‘basal’ insulin once or twice daily)

=> insulin aspart: NovoRapid
=> insulin lispro: Humalog

2. Short-acting insulins
   - onset: 30mins
   - peak: 3 hours
   - duration: 6-8 hours

=> soluble insulin examples: Actrapid (human, pyr), Humulin S (human, prb)

=> may be used as the bolus dose in ‘basal-bolus’ regimes

Answer 18

3. Intermidate-acting insulins
   - onset: 2hours
   - peak: 5-8 hours
   - duration: 12-18 hours

=> isophane insulin
*many patients use isophane insulin in a premixed formulation with

4. Long-acting insulins
   - onset: 1-2 hours
   - peak: flat profile
   - duration: unto 24 hours

=> insulin determir (Levemir): given once or twice daily

=> insulin glargine (Lantus): given once daily

5. Premixed preparations:
   Combine intermediate acting insulin with either a rapid-acting insulin analogue or soluble insulin

• imp to rotate injection site to prevent lipodystrophy
• Insulin pumps are available (‘continuous subcutaneous insulin infusions’) which delivers a continuous basal infusion and a patient-activated bolus dose at meal times.
• Intravenous insulin is used for patients who are acutely unwell, for example with diabetic ketoacidosis

Question 19

Common drugs and adverse effects of diabetes

Answer 19

1. Metformin
   => GI effects
   => Lactic acidosis

2. Sulfonylureas 
=> Hypoglycaemic episodes
=> Increased appetite and weight gain
=> Syndrome of inappropriate ADH secretion
=> Liver dysfunction (cholestatic)

3. Glitazones
=> Weight gain
=> Fluid retention
=> Liver dysfunction
=> Fractures

4. Gliptins
   => Pancreatitis

Question 20

Diabetes sick day rule:

1. Increase frequency of blood glucose monitoring to four hourly or more frequently
2. Encourage fluid intake aiming for at least 3 litres in 24hrs
3. If unable to take struggling to eat may need sugary drinks to maintain carbohydrate intake
4. Educate patients so that they have a box of ‘sick day supplies’ that they can access if they become unwell
   * Access to a mobile phone has been shown to reduce progression of ketosis to diabetic ketoacidosis

Answer 20

If a patient is taking oral hypoglycaemic medication, they should be advised to continue taking their medication even if they are not eating much.
=> Remember that the stress response to illness increases cortisol levels pushing blood sugars high even without much oral intake.

=> The possible exception is with metformin, which should be stopped if a patient is becoming dehydrated because of the potential impact upon renal function.

If a patient is on insulin, they must not stop it due to the risk of diabetic ketoacidosis. They should continue their normal insulin regime but ensure that they are checking their blood sugars frequently.

Patients should be able to check their ketone levels and if these are raised and blood sugars are also raised they may need to give corrective doses of insulin. The corrective dose to be given varies by patient, but a rule of thumb would be total daily insulin dose divided by 6 (maximum 15 units).

Question 21

Health promotion in diabetes: Diet and Exercise

Answer 21

DIET:
See early on

Exercise:
=> Regular exercise and physical activity
=> Aim to minimize time spent being inactive / sedentary
=> Advise that regular exercise may lower blood glucose levels, improve cardiovascular risk, and reduce excess weight (when combined with a healthy diet).

Provide information on the following (if appropriate):
=> effect of exercise on blood glucose levels when insulin levels are adequate (risk of hypoglycaemia).
=> effect of exercise on blood glucose levels when the person is hyperglycaemic (risk of worsening blood glucose control and ketones in the blood).
=> appropriate adjustments of insulin dosage and/or nutritional intake for exercise and post-exercise periods

Alcohol:
=> Advise on the recommended alcohol limits.
=> eat a snack that contains carbohydrate before and after drinking alcohol.
=> Educate that alcohol may exacerbate or prolong the hypoglycaemic effect of antidiabetic drugs.
=> The signs of hypoglycaemia may become less obvious, and delayed hypoglycaemia may occur up to several hours after alcohol consumption.
=> Advise the person to always wear or carry some form of diabetes identification, as reduced awareness of hypoglycaemia may be confused with alcohol intoxication, such as a:
MedicAlert® bracelet, necklace, or watch.
Diabetes identity card or wristband

Smoking:
=> smoking cessation - risk of CVD

Question 22

Diabetic foot:

1. It occurs secondary to two main factors:
   neuropathy: resulting in loss of protective sensation (e.g. not noticing a stone in the shoe), Charcot’s arthropathy, dry skin
2. Peripheral arterial disease: diabetes is a risk factor for both macro and microvascular ischaemia

Presentation:
=> neuropathy: loss of sensation
=> ischaemia: absent foot pulses, reduced ankle-brachial pressure index (ABPI), intermittent claudication
=> complications: calluses, ulceration, Charcot’s arthropathy, cellulitis, osteomyelitis, gangrene

Low risk:
No risk factors present except callus alone.

Moderate risk:
Deformity, or
Neuropathy, or
Non-critical limb ischaemia.

High risk:
Previous ulceration, or
Previous amputation, or
On renal replacement therapy, or
Neuropathy and non-critical limb ischaemia together, or
Neuropathy in combination with callus and/or deformity, or
Non-critical limb ischaemia in combination with callus and/or deformity.

Active diabetic foot problem:
Ulceration, or
Spreading infection, or
Critical limb ischaemia, or
Gangrene, or
Suspicion of an acute Charcot arthropathy, or an unexplained hot, red, swollen foot with or without pain.

Answer 22

For people who are at low risk of developing a diabetic foot problem, continue to carry out annual foot assessments, emphasize the importance of foot care, and advise that they could progress to moderate or high risk.

For people at moderate or high risk of developing a diabetic foot problem, refer to the foot protection service. They should be seen within 2–4 weeks if at high risk or within 6–8 weeks if at moderate risk.

For people with a limb-threatening or life-threatening diabetic foot problem, refer immediately to acute services, and inform the multidisciplinary foot care service

Reassessment:
Annually — for people who are at low risk.

Frequently (for example every 3–6 months) — for people who are at moderate risk.

More frequently (for example every 1–2 months) — for people who are at high risk, if there is no immediate concern. More frequent reassessments should be considered for people who are unable to check their own feet.

Very frequently (for example every 1–2 weeks) — for people who are at high risk, if there is immediate concern.