TRIPASS XR تري باس

Insulin requirements

g The dosage of insulin must be determined individually

for each patient and should be adjusted as necessary

according to the results of regular monitoring of bloodglucose concentrations. h

Persistent poor glucose control, leading to erratic insulin

requirements or episodes of hypoglycaemia, may be due to

many factors, including adherence, injection technique,

injection site problems, blood-glucose monitoring skills,

lifestyle issues (including diet, exercise and alcohol intake),

psychological issues, and organic causes such as renal

disease, thyroid disorders, coeliac disease, Addison’s disease

or gastroparesis.

Infection, stress, accidental or surgical trauma can all

increase the required insulin dose. Insulin requirements may

be decreased (and therefore susceptibility to hypoglycaemia

increased) by physical activity, intercurrent illness, reduced

food intake, impaired renal function, and in certain

endocrine disorders.

Risks of hypoglycaemia with insulin

g Hypoglycaemia is an inevitable adverse effect of insulin

treatment, and patients should be advised of the warning

signs and actions to take (for guidance on management, see

Hypoglycaemia p. 724).

Impaired awareness of hypoglycaemia can occur when the

ability to recognise usual symptoms is lost, or when the

symptoms are blunted or no longer present. Patients’

awareness of hypoglycaemia should be assessed annually

using the Gold score or the Clarke score. h

An increase in the frequency of hypoglycaemic episodes

may reduce the warning symptoms experienced by the

patient. Impaired awareness of symptoms below 3 mmol/litre

is associated with a significantly increased risk of severe

hypoglycaemia. Beta-blockers can also blunt hypoglycaemic

awareness, by reducing warning signs such as tremor.

Loss of warning of hypoglycaemia among insulin-treated

patients can be a serious hazard, especially for drivers and

those in dangerous occupations. Advice should be given in

line with the Driver and Vehicle Licensing Agency (DVLA)

guidance (see Driving under Diabetes p. 682).

g To restore the warning signs, episodes of

hypoglycaemia must be minimised. Insulin regimens, doses

and blood-glucose targets should be reviewed and

continuous subcutaneous insulin infusion therapy and realtime continuous blood-glucose monitoring should be

considered. Patients should receive structured education to

ensure they are following the principles of a flexible insulin

regimen correctly, with additional education regarding

avoiding and treating hypoglycaemia for those who continue

to have impaired awareness. Relaxation of individualised

blood-glucose targets should be avoided as a strategy to

improve impaired awareness of symptoms. If recurrent

severe episodes of hypoglycaemia continue despite

appropriate interventions, the patient should be referred to a

specialist centre. h

There is conflicting evidence regarding reports that some

patients may experience loss of awareness of hypoglycaemia

after transfer from animal to human insulin; clinical studies

do not confirm that human insulin decreases hypoglycaemia

awareness.

Manufacturers advise any switch between brands or

formulation of insulin (including switching from animal to

human insulin) should be done under strict supervision; a

change in dose may be required.

Hypodermic equipment

g Patients should be advised on the safe disposal of

lancets, single-use syringes, and needles, and should be

provided with suitable disposal containers. Arrangements

should be made for the suitable disposal of these containers.

h

Lancets, needles, syringes, and accessories are listed under

Hypodermic Equipment in Part IXA of the Drug Tariff (Part

III of the Northern Ireland Drug Tariff, Part 3 of the Scottish

Drug Tariff). The drug Tariffs can be access online at:

. National Health Service Drug Tariff for England and Wales:

www.nhsbsa.nhs.uk/pharmacies-gp-practices-and-appliancecontractors/drug-tariff

. Health and Personal Social Services for Northern Ireland

Drug Tariff:

www.hscbusiness.hscni.net/services/2034.htm

. Scottish Drug Tariff:

www.isdscotland.org/Health-Topics/Prescribing-and-Medicines/

Scottish-Drug-Tariff

Advanced Pharmacy Services

Patients with type 1 diabetes may be eligible for the

Medicines Use Review service provided by a community

pharmacist. For further information, see Advanced Pharmacy

Services in Guidance on prescribing p. 1.

Useful Resources

Type 1 diabetes in adults: diagnosis and management.

National Institute for Health and Care Excellence. Clinical

guideline NG17. August 2015.

www.nice.org.uk/guidance/ng17

Insulin 05-Jun-2017

Overview

For recommended insulin regimens see Type 1 diabetes

p. 684 and Type 2 diabetes p. 686.

Insulin is a polypeptide hormone secreted by pancreatic

beta-cells. Insulin increases glucose uptake by adipose tissue

and muscles, and suppresses hepatic glucose release. The

role of insulin is to lower blood-glucose concentrations in

order to prevent hyperglycaemia and its associated

microvascular, macrovascular and metabolic complications.

The natural profile of insulin secretion in the body consists

of basal insulin (a low and steady secretion of background

insulin that controls the glucose continuously released from

the liver) and meal-time bolus insulin (secreted in response

to glucose absorbed from food and drink).

Sources of insulin

Three types of insulin are available in the UK: human

insulin, human insulin analogues, and animal insulin.

Animal insulins are extracted and purified from animal

sources (bovine or porcine insulin). Although widely used in

the past, animal insulins are no longer initiated in people

with diabetes but may still be used by some adult patients

who cannot, or do not wish to, change to human insulins.

Human insulins are produced by recombinant DNA

technology and have the same amino acid sequence as

endogenous human insulin. Human insulin analogues are

produced in the same way as human insulins, but the insulin

is modified to produce a desired kinetic characteristic, such

as an extended duration of action or faster absorption and

onset of action.

Immunological resistance to insulin is uncommon and

true insulin allergy is rare. Human insulin and insulin

analogues are less immunogenic than animal insulins.

Administration of insulin

Insulin is inactivated by gastro-intestinal enzymes and must

therefore be given by injection; the subcutaneous route is

ideal in most circumstances. Insulin should be injected into a

body area with plenty of subcutaneous fat—usually the

abdomen (fastest absorption rate) or outer thighs/buttocks

(slower absorption compared with the abdomen or inner

thighs).

BNF 78 Diabetes mellitus 685

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Absorption from a limb site can vary considerably (by as

much as 20–40%) day-to-day, particularly in children. Local

tissue reactions, changes in insulin sensitivity, injection site,

blood flow, depth of injection, and the amount of insulin

injected can all affect the rate of absorption. Increased blood

flow around the injection site due to exercise can also

increase insulin absorption.

g Lipohypertrophy can occur due to repeatedly

injecting into the same small area, and can cause erratic

absorption of insulin, and contribute to poor glycaemic

control. Patients should be advised not to use affected areas

for further injection until the skin has recovered.

Lipohypertrophy can be minimised by using different

injection sites in rotation. Injection sites should be checked

for signs of infection, swelling, bruising, and

lipohypertrophy before administration. h

Insulin preparations

Insulin preparations can be broadly categorised into three

groups based on their time-action profiles: short-acting

insulins (including soluble insulin and rapid-acting insulins),

intermediate-acting insulins and long-acting insulins. The

duration of action of each particular type of insulin varies

considerably from one patient to another, and needs to be

assessed individually.

Short-acting insulins

Short-acting insulins have a short duration and a relatively

rapid onset of action, to replicate the insulin normally

produced by the body in response to glucose absorbed from a

meal. These are available as soluble Insulin p. 685 (human

and, bovine or porcine—both rarely used), and the rapidacting insulin analogues (insulin aspart p. 713, insulin

glulisine p. 714 and insulin lispro p. 714).

Soluble insulin

Soluble insulin is usually given subcutaneously but some

preparations can be given intravenously and

intramuscularly. For maintenance regimens, it is usual to

inject the insulin 15 to 30 minutes before meals, depending

on the insulin preparation used.

When injected subcutaneously, soluble insulin has a rapid

onset of action (30 to 60 minutes), a peak action between 1

and 4 hours, and a duration of action of up to 9 hours.

When injected intravenously, soluble insulin has a short

half-life of only a few minutes and its onset of action is

instantaneous.

Soluble insulin administered intravenously is the most

appropriate form of insulin for use in diabetic emergencies

e.g. Diabetic ketoacidosis p. 689 and peri-operatively.

Rapid-acting insulin

Insulin aspart, insulin glulisine, and insulin lispro have a

faster onset of action (within 15 minutes) and shorter

duration of action (approximately 2–5 hours) than soluble

insulin, and are usually given by subcutaneous injection.

g For maintenance regimens, these insulins should

ideally be injected immediately before meals. Rapid-acting

insulin, administered before meals, has an advantage over

short-acting soluble insulin in terms of improved glucose

control, reduction of HbA1c, and reduction in the incidence

of severe hypoglycaemia, including nocturnal

hypoglycaemia.

The routine use of post-meal injections of rapid-acting

insulin should be avoided—when given during or after meals,

they are associated with poorer glucose control, an increased

risk of high postprandial-glucose concentration, and

subsequent hypoglycaemia. h

Intermediate-acting insulin

Intermediate-acting insulins (isophane insulin p. 716) have

an intermediate duration of action, designed to mimic the

effect of endogenous basal insulin. When given by

subcutaneous injection, they have an onset of action of

approximately 1–2 hours, a maximal effect at 3–12 hours,

and a duration of action of 11–24 hours.

Isophane insulin is a suspension of insulin with

protamine; it may be given as one or more daily injections

alongside separate meal-time short-acting insulin

injections, or mixed with a short-acting (soluble or rapidacting) insulin in the same syringe—for recommended

insulin regimens see Type 1 diabetes p. 684 and Type 2

diabetes below. Isophane insulin may be mixed with a shortacting insulin by the patient, or a pre-mixed biphasic insulin

can be supplied (biphasic isophane insulin p. 715, biphasic

insulin aspart p. 716 and biphasic insulin lispro p. 716).

Biphasic insulins (biphasic isophane insulin, biphasic

insulin aspart, biphasic insulin lispro) are pre-mixed insulin

preparations containing various combinations of shortacting insulin (soluble insulin or rapid-acting analogue

insulin) and an intermediate-acting insulin.

The percentage of short-acting insulin varies from

15% to 50%. These preparations should be administered by

subcutaneous injection immediately before a meal.

Long-acting insulin

Like intermediate-acting insulins, the long-acting insulins

(protamine zinc insulin p. 719, insulin zinc suspension

p. 718, insulin detemir p. 717, insulin glargine p. 718, insulin

degludec p. 717) mimic endogenous basal insulin secretion,

but their duration of action may last up to 36 hours. They

achieve a steady-state level after 2–4 days to produce a

constant level of insulin.

Insulin glargine and insulin degludec are given once daily

and insulin detemir is given once or twice daily according to

individual requirements. The older long-acting insulins,

(insulin zinc suspension and protamine zinc insulin) are now

rarely prescribed.

Type 2 diabetes 10-May-2018

Description of condition

Type 2 diabetes is a chronic metabolic condition

characterised by insulin resistance. Insufficient pancreatic

insulin production also occurs progressively over time,

resulting in hyperglycaemia.

It is commonly associated with obesity, physical inactivity,

raised blood pressure, dyslipidaemia and a tendency to

develop thrombosis; therefore it increases cardiovascular

risk. It is associated with long-term microvascular and

macrovascular complications, together with reduced quality

of life and life expectancy.

Type 2 diabetes typically develops later in life but is

increasingly diagnosed in children, despite previously being

considered a disease of adulthood.

Aims of treatment

Treatment is aimed at minimising the risk of long-term

microvascular and macrovascular complications by effective

blood-glucose control and maintenance of HbA1c at or

below the target value set for each individual patient.

Overview

g Weight loss, smoking cessation and regular exercise

can help to reduce hyperglycaemia and reduce

cardiovascular risk, and should be encouraged (with input

from a dietitian where appropriate). For guidance on

reducing cardiovascular risk, see Cardiovascular disease risk

assessment and prevention p. 189. Antidiabetic drugs should

be prescribed to augment lifestyle interventions, when these

changes are not adequate to control blood-glucose alone.

h

686 Diabetes mellitus and hypoglycaemia BNF 78

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Antidiabetic drugs

There are several classes of non-insulin antidiabetic drugs

available for the treatment of type 2 diabetes.g The

choice of drug should be based on effectiveness, safety,

tolerability and should also take into consideration the

patient’s comorbidities and concomitant medication. For

recommended treatment regimens and the place in therapy

of each drug, see Drug treatment, antidiabetic drugs (below).

h

Metformin hydrochloride p. 692 has an antihyperglycaemic effect, lowering both basal and postprandial

blood-glucose concentrations. It does not stimulate insulin

secretion and therefore, when given alone, does not cause

hypoglycaemia.g The dose of standard-release

metformin hydrochloride should be increased gradually to

minimise the risk of gastro-intestinal side effects. Modifiedrelease metformin hydrochloride should be offered if

standard treatment is not tolerated. h

The sulfonylureas (glibenclamide p. 709, gliclazide p. 709,

glimepiride p. 709, glipizide p. 710, tolbutamide p. 710) may

cause hypoglycaemia; it is more likely with long-acting

sulfonylureas such as glibenclamide, which have been

associated with severe, prolonged and sometimes fatal cases

of hypoglycaemia. Sulfonylureas are also associated with

modest weight gain, probably due to increased plasmainsulin concentrations.

Acarbose p. 692 has a poorer anti-hyperglycaemic effect

than many other antidiabetic drugs, including the

sulfonylureas, metformin hydrochloride, and pioglitazone

p. 710.

The meglitinides, nateglinide p. 701 and repaglinide

p. 702, have a rapid onset of action and short duration of

activity. These drugs can be used flexibly around mealtimes

and adjusted to fit around individual eating habits which

may be beneficial for some patients, but generally are a less

preferred option than the sulfonylureas.

The thiazolidinedione, pioglitazone, is associated with

several long-term risks and its ongoing benefit to the patient

should be reviewed regularly and treatment stopped if

response is insufficient (see Important safety information

under pioglitazone).

The dipeptidylpeptidase-4 inhibitors (gliptins), alogliptin

p. 694, linagliptin p. 694, sitagliptin p. 696, saxagliptin

p. 695, and vildagliptin p. 697, do not appear to be associated

with weight gain and have less incidence of hypoglycaemia

than the sulfonylureas.

The sodium glucose co-transporter 2 inhibitors,

canagliflozin p. 702, dapagliflozin p. 704, and empagliflozin

p. 706, may be suitable for some patients when first-line

options are not appropriate.g Canagliflozin and

empagliflozin can be beneficial in patients with type 2

diabetes and established cardiovascular disease. h Sodium

glucose co-transporter 2 inhibitors are associated with a risk

of diabetic ketoacidosis.

The glucagon-like peptide-1 receptor agonists, dulaglutide

p. 698, exenatide p. 698, liraglutide p. 699 and lixisenatide

p. 700, should be reserved for combination therapy when

other treatment options have failed.g Liraglutide has

proven cardiovascular benefit and should be considered in

patients with type 2 diabetes and established cardiovascular

disease. h

Polycystic ovary syndrome

g Metformin hydrochloride (initiated by a specialist) is

prescribed as an insulin sensitising drug in women with

polycystic ovary syndrome who are not planning pregnancy

[unlicensed indication] h. Long-term benefit or superiority

over other treatment options has not been confirmed by

good quality evidence. Metformin hydrochloride may

improve short-term insulin sensitivity and reduce androgen

concentrations, but there is insufficient supporting evidence

that metformin improves weight gain, hirsutism, acne or

regulation of the menstrual cycle. Treatment should only be

initiated by a specialist. Metformin hydrochloride does not

exert a hypoglycaemic action in non-diabetic patients except

in overdose.

Drug treatment, antidiabetic drugs

g Type 2 diabetes should initially be treated with a single

oral antidiabetic drug. A target HbA1c concentration of

48 mmol/mol (6.5%) is generally recommended when type 2

diabetes is managed by diet and lifestyle alone or when

combined with a single antidiabetic drug not associated with

hypoglycaemia (such as metformin hydrochloride). Adults

prescribed a single drug associated with hypoglycaemia

(such as a sulphonylurea), or two or more antidiabetic drugs

in combination, should usually aim for an HbA1c

concentration of 53 mmol/mol (7.0%). Targets may differ and

should be individualised and agreed with each patient.

Note: Consider relaxing the target HbA1c level on a caseby-case basis, with particular consideration for people who

are older, frail, or where tight blood-glucose control is not

appropriate or poses a high risk of the consequences of

hypoglycaemia.

If HbA1c concentrations are poorly controlled despite

treatment with a single drug (usually considered to be a rise

of HbA1c to 58 mmol/mol (7.5%) or higher), the drug

treatment should be intensified, alongside reinforcement of

advice regarding diet, lifestyle, and adherence to drug

treatment.

When two or more antidiabetic drugs are prescribed, an

HbA1c concentration target of 53 mmol/mol (7.0%) is

recommended for patients in which it is appropriate, but a

relaxation of the target may be more appropriate in some

individual cases (for example, those at high risk of the

consequences of hypoglycaemia, poor life expectancy, or

significant comorbidities). h

Initial treatment

g Metformin hydrochloride is recommended as the first

choice for initial treatment for all patients, due to its positive

effect on weight loss, reduced risk of hypoglycaemic events

and the additional long-term cardiovascular benefits

associated with its use. h

If metformin is contra-indicated or not tolerated, see

Alternative non-metformin regimens below.

First intensification of treatment

g If metformin hydrochloride (alongside modification to

diet) does not control HbA1c to below the agreed threshold,

treatment should be intensified, and metformin

hydrochloride combined with one of the following:

. a sulfonylurea (glibenclamide, gliclazide, glimepiride,

glipizide, tolbutamide) ;

. Pioglitazone;

. a dipeptidylpeptidase-4 inhibitor (linagliptin, saxagliptin,

sitagliptin, or vildagliptin);

. a sodium glucose co-transporter 2 inhibitor (canagliflozin,

dapagliflozin or empagliflozin) only when sulfonylureas

are contra-indicated or not tolerated, or if the patient is at

significant risk of hypoglycaemia or its consequences. h

g Elderly patients or those with renal impairment are at

particular risk of hypoglycaemia; if a sulfonylurea is

indicated, a shorter-acting sulfonylurea, such as gliclazide

p. 709 or tolbutamide p. 710 should be prescribed. l

The place in therapy of alogliptin p. 694 (a

dipeptidylpeptidase-4 inhibitor) is not yet known.

Second intensification of treatment

g If dual therapy is unsuccessful, treatment should be

intensified again, and one of the following triple therapy

regimens prescribed:

. Metformin hydrochloride p. 692 and a

dipeptidylpeptidase-4 inhibitor and a sulfonylurea;

. Metformin hydrochloride and pioglitazone p. 710 and a

sulfonylurea;

BNF 78 Diabetes mellitus 687

Endocrine system

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. Metformin hydrochloride and a sulfonylurea and one of

the sodium glucose co-transporter 2 inhibitors;

. Metformin hydrochloride and pioglitazone and a sodium

glucose co-transporter 2 inhibitor (canagliflozin p. 702 or

empagliflozin p. 706; note that dapagliflozin is not

recommended in a triple therapy regimen with

pioglitazone).

Alternatively, it may be appropriate to start insulinbased treatment at this stage—see Drug treatment, insulin.

h

Glucagon-like peptide-1 receptor agonists

g If triple therapy with metformin hydrochloride and two

other oral drugs is tried and is not effective, not tolerated or

contra-indicated, a glucagon-like peptide-1 receptor

agonist may be prescribed as part of a triple combination

regimen with metformin hydrochloride and a sulfonylurea.

These should only be prescribed for patients who have a

BMI of 35 kg/m2

or above (adjusted for ethnicity) and who

also have specific psychological or medical problems

associated with obesity; or for those who have a BMI lower

than 35 kg/m2 but for whom insulin therapy would have

significant occupational implications or if the weight loss

associated with glucagon-like peptide-1 receptor agonists

would benefit other significant obesity-related

comorbidities.

After 6 months, the drug should be reviewed and only

continued if there has been a beneficial metabolic response

(a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a

weight loss of at least 3% of initial body-weight).

Insulin should only be prescribed in combination with a

glucagon-like peptide-1 receptor agonist under specialist

care advice and with ongoing support from a consultant-led

multidisciplinary team. h

Alternative non-metformin regimens

g If metformin is contra-indicated or not tolerated, initial

treatment should be single therapy with:

. a sulfonylurea (glibenclamide p. 709, gliclazide,

glimepiride p. 709, glipizide p. 710, or tolbutamide) (first

choice) or

. a dipeptidyl peptidase-4 inhibitor (linagliptin p. 694,

saxagliptin p. 695, sitagliptin p. 696, or vildagliptin p. 697),

or

. Pioglitazone.h

The sodium glucose co-transporter 2 inhibitors

canagliflozin, dapagliflozin p. 704, or empagliflozin are also

options for monotherapy when metformin is contraindicated or not tolerated, only if a dipeptidylpeptidase-4

inhibitor would otherwise be prescribed and neither a

sulfonylurea nor pioglitazone is appropriate.

g Repaglinide p. 702 is also an effective alternative

option for single therapy, but it has a limited role in

treatment because, should an intensification of treatment be

required, it is not licensed to be used in any combination

other than with metformin hydrochloride; it would therefore

require a complete change of treatment in those patients

who have started it due to intolerance or contra-indication

to metformin. h

Intensification

g If the initial single drug does not control HbA1c to

below the agreed threshold, treatment should be intensified

and one of the following dual combinations prescribed:

. a dipeptidylpeptidase-4 inhibitor and pioglitazone;

. a dipeptidylpeptidase-4 inhibitor and a sulfonylurea; or

. Pioglitazone and a sulfonylurea .

If dual therapy does not provide adequate glucose control,

insulin-based treatment should be considered—see Drug

treatment, insulin. h

Drug treatment, insulin

g When indicated for intensification, insulin (see also,

Insulin p. 685) should be started with a structured support

programme covering insulin dose titration, injection

technique, self-monitoring, and knowledge of dietary effects

and glucose control. Metformin hydrochloride should be

continued unless it is contra-indicated or not tolerated.

Other antidiabetic drugs should be reviewed and stopped if

necessary.

Recommended insulin regimens include:

. human isophane insulin p. 716 injected once or twice

daily, according to requirements;

. a human isophane insulin in combination with a shortacting insulin, administered either separately or as a premixed (biphasic) human insulin preparation (this may be

particularly appropriate if HbA1c is 75 mmol/mol (9.0%) or

higher);

. Insulin detemir p. 717 or insulin glargine p. 718 as an

alternative to human isophane insulin. This can be

preferable if a once daily injection would be beneficial (for

example if assistance is required to inject insulin), or if

recurrent symptomatic hypoglycaemic episodes are

problematic, or if the patient would otherwise need twicedaily human isophane insulin injections in combination

with oral glucose-lowering drugs. Also consider switching

to insulin detemir or insulin glargine from human

isophane insulin if significant hypoglycaemia is

problematic, or in patients who cannot use the device

needed to inject human isophane insulin;

. biphasic preparations (pre-mixed) that include a shortacting human analogue insulin (rather than short-acting

human soluble insulin) can be preferable for patients who

prefer injecting insulin immediately before a meal, or if

hypoglycaemia is a problem, or if blood-glucose

concentrations rise markedly after meals.

When starting insulin therapy, bedtime basal insulin

should be initiated and the dose titrated against morning

(fasting) glucose. Patients who are prescribed a basal insulin

regimen (human isophane insulin, insulin detemir or insulin

glargine) should be monitored for the need for short-acting

insulin before meals (or a biphasic insulin preparation).

Patients who are prescribed a biphasic insulin should be

monitored for the need for a further injection of short-acting

insulin before meals or for a change to a basal-bolus regimen

with human isophane insulin or insulin detemir or insulin

glargine if blood-glucose control remains inadequate. h

Advanced Pharmacy Services

Patients with type 2 diabetes may be eligible for the New

Medicines Service / Medicines Use Review service provided

by a community pharmacist. For further information, see

Advanced Pharmacy Services in Guidance on prescribing p. 1.

Useful Resources

Type 2 diabetes in adults: management. National Institute

for Health and Care Excellence. Clinical guideline NG28.

December 2015.

www.nice.org.uk/guidance/ng28

Pharmacological management of glycaemic control in

people with type 2 diabetes. Scottish Intercollegiate

Guidelines Network. Clinical guideline 154. November 2017.

www.sign.ac.uk/assets/sign154.pdf

Diabetic complications 10-May-2018

See also

Diabetes p. 682

Type 1 diabetes p. 684

Type 2 diabetes p. 686

Diabetes and cardiovascular disease

Diabetes is a strong risk factor for cardiovascular disease.

g Other risk factors for cardiovascular disease that should

688 Diabetes mellitus and hypoglycaemia BNF 78

Endocrine system

6

also be addressed are: smoking, hypertension, obesity, and

dyslipidaemia. hCardiovascular risk in patients with

diabetes can be further reduced by the use of an ACE

inhibitor (or an angiotensin-II receptor antagonist) and

lipid-regulating drugs. For full guidance on the assessment

and prevention of cardiovascular disease, see Cardiovascular

disease risk assessment and prevention p. 189.

Diabetic nephropathy

g In diabetic patients with nephropathy, blood pressure

should be reduced to the lowest achievable level to slow the

rate of decline of glomerular filtration rate and reduce

proteinuria. Provided there are no contra-indications, all

diabetic patients with nephropathy causing proteinuria or

with established microalbuminuria should be treated with an

ACE inhibitor or an angiotensin-II receptor antagonist, even

if the blood pressure is normal. ACE inhibitors or

angiotensin-II receptor antagonists should also be given as

monotherapy, or combined therapy, in patients with chronic

kidney disease and proteinuria, to reduce the rate of

progression of chronic kidney disease. h

ACE inhibitors can potentiate the hypoglycaemic effect of

insulin and oral antidiabetic drugs; this effect is more likely

during the first weeks of combined treatment and in patients

with renal impairment.

See also treatment of hypertension in diabetes in

Hypertension p. 140.

Diabetic neuropathy

g Optimal diabetic control is beneficial for the

management of painful neuropathy. Monotherapy with

antidepressant drugs, including tricyclics (such as

amitriptyline hydrochloride p. 372 and imipramine

hydrochloride p. 376 [unlicensed use]), duloxetine p. 367,

and venlafaxine p. 368 [unlicensed use] should be considered

in patients for the treatment of painful diabetic peripheral

neuropathy. Antiepileptic drugs, such as pregabalin p. 324

and gabapentin p. 315, can also be considered. Opioid

analgesics in combination with gabapentin can be

considered if pain is not controlled with monotherapy. h

In autonomic neuropathy, diabetic diarrhoea can often be

managed by tetracycline p. 567 [unlicensed use], or codeine

phosphate p. 454 as the best alternative; other

antidiarrhoeal preparations can also be tried. Erythromycin

p. 539 (especially when given intravenously) may be

beneficial for gastroparesis [unlicensed use].

In neuropathic postural hypotension, increased salt intake

and the use of the mineralcorticoid fludrocortisone acetate

p. 676 [unlicensed use] may help by increasing plasma

volume, but uncomfortable oedema is a common side-effect.

Fludrocortisone can also be combined with flurbiprofen

p. 1140 and ephedrine hydrochloride p. 272 [both

unlicensed]. Midodrine [unlicensed], an alpha agonist, may

also be useful in postural hypotension.

Gustatory sweating can be treated with an antimuscarinic

such as propantheline bromide p. 86; side-effects are

common. See also, the management of hyperhidrosis

(Hyperhidrosis p. 1264).

In some patients with neuropathic oedema, ephedrine

hydrochloride [unlicensed use] offers effective relief.

See also the management of Erectile dysfunction p. 812.

Visual impairment

g Optimal diabetic control (HbA1c ideally around 7% or

53 mmol/mol) and blood pressure control (<130/80 mmHg)

should be maintained to prevent onset and progression of

diabetic eye disease. h

Diabetic ketoacidosis

Management

The management of diabetic ketoacidosis involves the

replacement of fluid and electrolytes and the administration

of insulin. Guidelines for the Management of Diabetic

Ketoacidosis in Adults, published by the Joint British

Diabetes Societies Inpatient Care Group (available at

www.diabetes.org.uk/Professionals/Position-statements-reports/

Specialist-care-for-children-and-adults-and-complications/TheManagement-of-Diabetic-Ketoacidosis-in-Adults/), should be

followed.

. To restore circulating volume if systolic blood pressure is

below 90 mmHg (adjusted for age, sex, and medication as

appropriate), give 500 mL sodium chloride 0.9% by

intravenous infusion over 10–15 minutes; repeat if blood

pressure remains below 90 mmHg and seek senior medical

advice.

. When blood pressure is over 90 mmHg, sodium chloride

0.9% should be given by intravenous infusion at a rate that

replaces deficit and provides maintenance; see guideline

or suggested regimen.

. Include potassium chloride in the fluids unless anuria is

suspected; adjust according to plasma-potassium

concentration (measure at 60 minutes, 2 hours, and

2 hourly thereafter; measure hourly if outside the normal

range).

. Start an intravenous insulin infusion: soluble insulin

should be diluted (and mixed thoroughly) with sodium

chloride 0.9% intravenous infusion to a concentration of

1 unit/mL; infuse at a fixed rate of 0.1 units/kg/hour.

. Established subcutaneous therapy with long-acting insulin

analogues (insulin detemir p. 717 or insulin glargine

p. 718) should be continued during treatment of diabetic

ketoacidosis.

. Monitor blood-ketone and blood-glucose concentrations

hourly and adjust the insulin infusion rate accordingly.

Blood-ketone concentration should fall by at least

0.5 mmol/litre/hour and blood-glucose concentration

should fall by at least 3 mmol/litre/hour.

. Once blood-glucose concentration falls below

14 mmol/litre, glucose 10% should be given by

intravenous infusion (into a large vein through a largegauge needle) at a rate of 125 mL/hour, in addition to the

sodium chloride 0.9% infusion.

. Continue insulin infusion until blood-ketone

concentration is below 0.3 mmol/litre, blood pH is above

7.3 and the patient is able to eat and drink; ideally give

subcutaneous fast-acting insulin and a meal, and stop the

insulin infusion 1 hour later.

The management of hyperosmolar hyperglycaemic state or

hyperosmolar hyperglycaemic nonketotic coma is similar to

that of diabetic ketoacidosis, although lower rates of insulin

infusion are usually necessary and slower rehydration may

be required.

Diabetes, surgery and medical

illness 05-Jun-2017

Management of diabetes during surgery

Peri-operative management of blood-glucose concentrations

depends on factors including the required duration of

fasting, timing of surgery (morning or afternoon), usual

treatment regimen (insulin, antidiabetic drugs or diet), prior

glycaemic control, other co-morbidities, and the likelihood

that the patient will be capable of self-managing their

diabetes in the immediate post-operative period.g All

patients should have emergency treatment for

hypoglycaemia written on their drug chart on admission. l

BNF 78 Diabetes mellitus 689