Diabetes mellitus: management of type 1

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.

NICE released guidelines on the diagnosis and management of type 1 diabetes in 2015. We've
only highlighted a very select amount of the guidance here which will be useful for any clinician
looking after a patient with type 1 diabetes.

HbA1c
● should be monitored every 3-6 months
● adults should have a target of HbA1c level of 48 mmol/mol (6.5%) or lower. NICE do
however recommend taking into account factors such as the person's daily activities,
aspirations, likelihood of complications, comorbidities, occupation and history of
hypoglycaemia

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

Blood glucose targets

● 5-7 mmol/l on waking and
● 4-7 mmol/l before meals at other times of the day

Type of insulin
● 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
● twice-daily insulin detemir is the regime of choice. Once-daily insulin glargine or insulin
detemir 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 with type 1 diabetes

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

DIABETES MELLITUS TYPE 2 : MANAGEMENT

Dietary advice
 ● Encourage high fibre, low glycaemic index sources of carbohydrates
● Include low-fat dairy products and oily fish
● Control the 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%

HbA1c targets

This is an area which has changed in 2015

individual targets should be agreed with patients to encourage motivation
HbA1c should be checked every 3-6 months until stable, then 6 monthly
NICE encourage us to consider relaxing targets on 'a case-by-case basis, with particular consideration for
people who are older or frail, for adults with type 2 diabetes'
in 2015 the guidelines changed so HbA1c targets are now dependent on treatment:

Lifestyle or single-drug treatment

Lifestyle 48 mmol/mol(6.5%)

Lifestyle + metformin 48 mmol/mol(6.5%)

Includes any drug which may cause hypoglycemia (e.g. lifestyle + 53 mmol/mol
sulfonylurea) (7.0%)

Initial drug therapy

● Metformin remains the first-line drug of choice in type 2 diabetes mellitus
● Metformin should be titrated up slowly to minimise the possibility of gastrointestinal upset
● If standard-release metformin is not tolerated then modified-release metformin should be
trialled

If metformin is contraindicated
● If the patient has a risk of CVD, established CVD or chronic heart failure : SGLT-2
● If the patient doesn't have a risk of CVD, established CVD or chronic heart failure : DPP-4i
or pioglitazone or a sulfonylurea

Further drug therapy if HbA1c targets are not met

● If HbA1c has risen to 58 mmol/mol (7.5%) then further treatment is indicated
● Second-line therapy
○ Metformin + DPP-4 inhibitor
○ Metformin + pioglitazone
○ Metformin + sulfonylurea
○ Metformin + SGLT-2 inhibitor (if NICE criteria met)
● Third-line therapy
○ 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
● Further therapy : If triple therapy is not effective or tolerated consider switching one of the
drugs for a GLP-1 mimetic:
○ BMI ≥ 35 kg/m² & specific psychological or other medical problems associated with
obesity OR
○ BMI < 35 kg/m² & for whom insulin therapy would have significant occupational implications
or weight loss would benefit other significant obesity-related comorbidities
○ Only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c & a weight loss
of at least 3% of initial body weight in 6 months
○ GLP-1 mimetics should only be added to insulin under specialist care

SGLT-2 inhibitors
● Metformin should be established & titrated up before introducing SGLT-2 inhibitor
● SGLT-2 inhibitors should also be started at any point if a patient develops CVD (e.g. is
diagnosed with ischaemic heart disease), a QRISK ≥ 10% or chronic heart failure

Starting insulin
● Metformin should be continued.
● NICE recommend starting with human NPH insulin (isophane, intermediate-acting) taken at bed-
time or twice daily according to need

Risk factor modification

● Hypertension
● blood pressure targets are the same as for patients without type 2 diabetes (see table below)
● 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
●
● Clinic BP ABPM / HBPM
● Age < 80 years 140/90 mmHg 135/85 mmHg
● Age > 80 years 150/90 mmHg 145/85 mmHg
●
● Antiplatelets
● should not be offered unless a patient has existing cardiovascular disease
●
● Lipids
● following the 2014 NICE lipid modification guidelines only patients with a 10-year cardiovascular risk
> 10% (using QRISK2) should be offered a statin. The first-line statin of choice is atorvastatin 20mg
on
● NICE recommends that people with type 1 diabetes should aim for 5-7mmol/litre on waking, 4-
7mmol/litre before meals and 5-9mmol/litre 90 minutes after eating.

Metformin : Indirect AMP kinase activator

MODY
MODY 2
● 20% of cases
● due to a defect in glucokinase gene
MODY 3
● 60% of cases
● Due to a defect in HNF-1 alpha gene
● Associated with an increased risk of HCC
● Very sensitive to low dose sulfonylureas, insulin is not usually necessary

MODY 5
● rare
● due to a defect in the HNF-1 beta gene
● Liver and renal cysts

Features of MODY
● Typically develops in patients < 25 years
● Family history of early onset diabetes is often present
● ketosis is not a feature at presentation

Impaired fasting glucose and impaired glucose tolerance

● impaired fasting glucose (IFG) - due to hepatic insulin resistance
● impaired glucose tolerance (IGT) - due to muscle insulin resistance
● patients with IGT are more likely to develop T2DM & cardiovascular disease than patients
with IFG

GESTATIONAL DIABETES MELLITUS

Screening for gestational diabetes

● OGTT is the test of choice
● Women with previous gestational diabetes: OGTT should be performed as soon as possible
after booking and at 24-28 weeks if the first test is normal
● Women with any of the other risk factors : OGTT at 24-28 weeks

Gestational diabetes is diagnosed if either:

● fasting glucose is >= 5.6 mmol/L
● 2-hour glucose is >= 7.8 mmol/L

Management
● FBG < 7 mmol/l
○ trial of diet and exercise should be offered
○ if glucose targets are not met within 1-2 weeks : metformin should be started
○ if glucose targets are still not met : insulin should be added
○ gestational diabetes is treated with short-acting, not long-acting, insulin
● FBG >= 7 mmol/l
○ Insulin should be started
● FBG 6-6.9 mmol/l with evidence of complications such as macrosomia or
hydramnios
 ○ Insulin should be offered
○ Glibenclamide should only be offered for women who cannot tolerate metformin or
those who fail to meet the glucose targets with metformin but decline

● Whose glucose returns to normal after birth need a postnatal glucose check 6-13 weeks
postpartum to stratify their risk of developing diabetes in the future
● NICE recommends that this is a fasting blood glucose
● Further follow up will depend on the result of this postnatal check
● Even if postnatal glucose is less than 6 mmol/l, annual fasting glucose checks are still
recommended thereafter.

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) may be a complication of existing type 1 diabetes mellitus or be the
first presentation, accounting for around 6% of cases. Rarely, under conditions of extreme stress,
patients with type 2 diabetes mellitus may also develop DKA.

Whilst DKA remains a serious condition mortality rates have decreased from 8% to under 1% in
the past 20 years.

Pathophysiology
DKA is caused by uncontrolled lipolysis (not proteolysis) which results in an excess of free fatty
acids that are ultimately converted to ketone bodies

Most common precipitating factors

● Infection
● Missed insulin doses
● Myocardial infarction.

Features
abdominal pain
polyuria, polydipsia, dehydration
Kussmaul respiration (deep hyperventilation)
Acetone-smelling breath ('pear drops' smell)

Diagnostic criteria

American Diabetes Association (2009) Joint British Diabetes Societies (2013)

Key points
glucose > 13.8 mmol/l
pH < 7.30
serum bicarbonate <18 mmol/l
anion gap > 10
ketonaemia
Key points
glucose > 11 mmol/l or known diabetes mellitus
pH < 7.3
bicarbonate < 15 mmol/l
ketones > 3 mmol/l or urine ketones ++ on dipstick

Parameters indicate severe diabetic ketoacidosis

● pH < 7
● Bicarbonate < 5 mmol/L
● Blood ketone > 6 mmol/L
● Anion gap >16 mmol/l
● Potassium < 3.5 mmol/L on admission
● Tachycardia or bradycardia
● SBP <90 mmHg
● Oxygen saturation < 92% on air
● GCS < 12

MANAGEMENT

Main principles of management

● Fluid replacement
○ Most patients with DKA are deplete around 5-8 litres
○ Isotonic saline is used initially, even if the patient is severely acidotic
● Insulin
○ An IV infusion should be started at 0.1 unit/kg/hour
○ Once blood glucose < 14 mmol/l : Infusion of 10% dextrose should be started at 125
ml/hr in addition to 0.9% sodium chloride regime
○ Long-acting insulin should be continued, short-acting insulin should be stopped
● Correction of electrolyte disturbance
○ Serum potassium is often high on admission despite total body potassium being low
○ This often falls quickly following treatment with insulin resulting in hypokalaemia
○ Potassium may therefore need to be added to the replacement fluids
○ If the rate of K infusion is > 20 mmol/h then cardiac monitoring may be required

Potassium level in first 24 hours (mmol/L) Potassium replacement in mmol/L of infusion

solution
Over 5.5 Nil
3.5-5.5 40
Below 3.5 Senior review as additional potassium needs to be given

JBDS example of fluid replacement regime for patient with a systolic BP on admission 90mmHg
and over

Fluid Volume
 ● 0.9% sodium chloride 1L 1000ml over 1st hour
● 0.9% sodium chloride 1L with potassium chloride 1000ml over next 2 hours
● 0.9% sodium chloride 1L with potassium chloride 1000ml over next 2 hours
● 0.9% sodium chloride 1L with potassium chloride 1000ml over next 4 hours
● 0.9% sodium chloride 1L with potassium chloride 1000ml over next 4 hours
● 0.9% sodium chloride 1L with potassium chloride 1000ml over next 6 hours

Please note that slower infusion may be indicated in young adults (aged 18-25 years) as they are
at greater risk of cerebral oedema.

JBDS potassium guidelines

Resolution
● DKA resolution is defined as
○ pH >7.3 and
○ Blood ketones < 0.6 mmol/L and
○ Bicarbonate > 15.0mmol/L
● If the above criteria are met & patient is eating & drinking switch to subcutaneous insulin
● Both ketonaemia & acidosis should have been resolved within 24 hours. If this hasn't
happened the patient requires senior review from an endocrinologist
● Patient should be reviewed by the diabetes specialist nurse prior to discharge

Complications
● Gastric stasis
● Thromboembolism
● Arrhythmias secondary to hyperkalaemia / iatrogenic hypokalaemia
● Iatrogenic due to incorrect fluid therapy : Cerebral oedema*, hypokalaemia, hypoglycaemia
● Acute respiratory distress syndrome
● Acute kidney injury

* children/young adults are particularly vulnerable to cerebral oedema following fluid resuscitation
in DKA and often need 1:1 nursing to monitor neuro-observations, headache, irritability, visual
disturbance, focal neurology etc. It usually occurs 4-12 hours following commencement of
treatment but can present at any time. If there is any suspicion a CT head and senior review
should be sought

● A patient with recurrent admissions for DKA can be started on degludec to reduce
readmission rate

HYPEROSMOLAR HYPERGLYCEMIC STATE (HHS)

 ● HHS typically presents in the elderly with type 2 diabetes mellitus (T2DM)
● Pathophysiology : Hyperglycaemia → ↑ serum osmolality → osmotic diuresis →
severe volume depletion

Precipitating factors
● Intercurrent illness
● Dementia
● Sedative drugs

Clinical features
● Whilst DKA presents within hours of onset, HHS comes on over many days &
consequently, dehydration & metabolic disturbances may be more extreme
● Clinical signs of dehydration
● Polyuria, polydipsia
● Lethargy, nausea and vomiting
● Altered level of consciousness, focal neurological deficits
● Hyperviscosity (may result in myocardial infarctions, stroke & peripheral arterial thrombosis)

There are no precise diagnostic criteria but the following are typically seen
● Hypovolaemia
● Marked hyperglycemia (>30 mmol/L)
● Significantly raised serum osmolarity (> 320 mosmol/kg)
○ Can be calculated by : 2 * Na+ + glucose + urea
● No significant hyperketonemia (<3 mmol/L)
● No significant acidosis (bicarbonate > 15 mmol/l or pH > 7.3 – acidosis can occur due to
lactic acidosis or renal impairment)

Management
● Fluid replacement
○ 0.9% saline is the recommended initial resuscitation fluid
○ Fluid losses in HHS are estimated to be between 100 - 220 ml/kg
○ Potassium levels should be monitored and added to fluids depending on the level
● Insulin
○ Should not be given unless blood glucose stops falling while giving IV fluids
● Venous thromboembolism prophylaxis
○ Patients are at risk of thrombosis due to hyperviscosity

Complications
● Vascular complications may occur due to hyperviscosity such as myocardial infarction,
stroke

Hypoglycaemia

Causes
insulinoma - increased ratio of proinsulin to insulin
self-administration of insulin/sulphonylureas
liver failure
Addison's disease
alcohol
causes exaggerated insulin secretion
mechanism is thought to be due to the effect of alcohol on the pancreatic
microcirculation → redistribution of pancreatic blood flow from the exocrine into the
endocrine parts → increased insulin secretion
nesidioblastosis - beta cell hyperplasia

Physiological response to hypoglycaemia

hormonal response: the first response of the body is decreased insulin secretion. This is followed
by increased glucagon secretion. Growth hormone and cortisol are also released but later
sympathoadrenal response: increased catecholamine-mediated (adrenergic) and acetylcholine-
mediated (cholinergic) neurotransmission in the peripheral autonomic nervous system and in the
central nervous system

Features
blood glucose levels and the severity of symptoms are not always correlated, especially in patients
with diabetes.
blood glucose concentrations <3.3 mmol/L cause autonomic symptoms due to the release of
glucagon and adrenaline (average frequency in brackets):
Sweating
Shaking
Hunger
Anxiety
Nausea
blood glucose concentrations below <2.8 mmol/L cause neuroglycopenic symptoms due to
inadequate glucose supply to the brain:
Weakness
Vision changes
Confusion
Dizziness
Severe and uncommon features of hypoglycaemia include:
Convulsion
Coma

Management of hypoglycaemia
● In community (for example, diabetes mellitus patients who inject insulin):
○ Initially, oral glucose 10-20g should be given in liquid, gel or tablet form
○ Alternatively, propriety quick-acting carbohydrate may be given : GlucoGel or
Dextrogel.
○ A 'HypoKit' may be prescribed which contains a syringe & vial of glucagon for IM or
SC injection at home
● In a hospital setting:
○ If patient is alert, a quick-acting carbohydrate may be given (as above)
○ If patient is unconscious or unable to swallow : S/C or IM glucagon may be given.
○ Alternatively, IV 20% glucose solution may be given through a large vein
 ● In sulphonylurea overdoses, if the patient remains hypoglycaemic despite infusion of
sufficient glucose, consider administration of octreotide
○ Octreotide blocks insulin secretion.

SGLT-2 inhibitors

SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal

proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose
excretion.

Examples include canagliflozin, dapagliflozin and empagliflozin.

Important adverse effects include

● urinary and genital infection (secondary to glycosuria). Fournier’s gangrene has also been
reported
● normoglycaemic ketoacidosis
● increased risk of lower-limb amputation: feet should be closely monitored

Patients taking SGLT-2 drugs often lose weight, which can be beneficial in type 2 diabetes
mellitus.
In CKD

● Without established CVD : Avoid initiation if eGFR < 60 mL/minute/1.73 m2 & discontinue
if eGFR falls to < 45 mL/minute/1.73 m2.
● In patients with established CVD : Avoid if eGFR < 30 mL/minute/1.73 m2.

When used for symptomatic chronic heart failure:

In patients with or without type 2 diabetes mellitus, avoid if eGFR less than 20
mL/minute/1.73 m2.

THIAZOLIDINEDIONES

● PPAR-gamma receptor agonist

○ An intracellular nuclear receptor > Control adipocyte differentiation and function.
● Reduce peripheral insulin resistance

Adverse effects
● Weight gain
● Liver impairment: Monitor LFTs
● Fluid retention
○ Contraindicated in heart failure
○ Risk of fluid retention is increased if the patient also takes insulin
 ● Increased risk of fractures
● Bladder cancer

DVLA : DIABETES MELLITUS

Until recently people with diabetes who used insulin could not hold a HGV licence. The DVLA
changed the rules in October 2011. The following standards need to be met (and also apply to
patients using other hypoglycaemic inducing drugs such as sulfonylureas):
● there has not been any severe hypoglycaemic event in the previous 12 months
● the driver has full hypoglycaemic awareness
● the driver must show adequate control of the condition by regular blood glucose
monitoring*, at least twice daily and at times relevant to driving
● the driver must demonstrate an understanding of the risks of hypoglycaemia
● here are no other debarring complications of diabetes

From a practical point of view patients on insulin who want to apply for a Group 2 (HGV) licence
need to complete a VDIAB1I form.

Other specific points for group 1 drivers:

● if on insulin then patient can drive a car as long as they have hypoglycaemic awareness,
not more than one episode of hypoglycaemia requiring the assistance of another person
within the preceding 12 months and no relevant visual impairment. Drivers are normally
contacted by DVLA
● if on tablets or exenatide no need to notify DVLA. If tablets may induce hypoglycaemia
(e.g. sulfonylureas) then there must not have been more than one episode of
hypoglycaemia requiring the assistance of another person within the preceding 12 months
● if diet controlled alone then no requirement to inform DVLA

*to demonstrate adequate control, the Secretary of State's Honorary Medical Advisory Panel on
Diabetes Mellitus has recommended that applicants will need to have used blood glucose meters
with a memory function to measure and record blood glucose levels for at least 3 months prior to
submitting their application