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Management of Type 1 and Type 2 Diabetes Requiring Insulin

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Management of Type 1 and Type 2 Diabetes Requiring Insulin ■ DRUG REVIEW Management of type 1 and type 2 diabetes requiring insulin DOROTHY ABIOLA, THOZHUKAT SATHYAPALAN, DAVID HEPBURN Insulin is a required therapy for people Symptomatic (ie polyruria, polydipsia, unexplained weight with type 1 diabetes, and its use in the loss) treatment of type 2 diabetes has been • Single fasting plasma glucose ≥7mmol/L increasing in recent years. This article • Single random plasma glucose ≥11.1mmol/L discusses the main types of insulin Asymptomatic currently available, their properties and • A fasting plasma glucose ≥7mmol/L on two separate their role in the management of both occasions OR • A random plasma glucose ≥11.1mmol/L on two separate type 1 and type 2 diabetes. occasions OR • An HbA1c ≥48mmol/mol (6.5%) on two separate occasions OR • An HbA1c ≥48mmol/mol AND a single elevated plasma glucose (fasting ≥7mmol/L or random ≥11.1mmol/L) Note: HbA1c cannot be used for type 1 diabetes diagnosis An HbA1c <48mmol/mol does not exclude type 2 diabetes Table 1. Diagnostic criteria for diabetes mellitus, based on the WHO’s 2006 Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycaemia and 2011 Use of Glycated Haemoglobin in the Diagnosis of Diabetes Mellitus iabetes mellitus is a common chronic condition character- Dised by absolute or relative insulin deficiency, and its prev- alence is increasing across the Western world and developing countries. This is particularly true of type 2 diabetes mellitus (T2DM) and UK data from the Quality and Outcomes Framework (QOF), published in 2015, showed there to be almost 3.5 mil- lion people in the UK with a diagnosis of diabetes.1 Diabetes costs the NHS close to £10 billion annually, with the majority of this cost going towards the treatment of diabetes-related com- plications.2 Furthermore, it is suspected that there are at least 590,000 people in the UK with undiagnosed T2DM.2 This review discusses the role of insulin therapy in type 1 diabetes mellitus (T1DM) and T2DM in the UK, including current guidelines and management options. Table 1 shows the current recommendations from the WHO for the diagnosis of diabetes mellitus. Type 1 diabetes mellitus T1DM makes up approximately 10 per cent of all cases of diabetes mellitus and reduces life expectancy by up to 13 years.3 T1DM can occur at any age, but is usually diagnosed in children and adolescents1 and its incidence has been ris- ing steadily in developed countries since the 1950s.4 It is 50 ❚ Prescriber September 2016 prescriber.co.uk Insulin l DRUG REVIEW ■ caused by the absolute lack of insulin production due to auto- • On clinical grounds: immune destruction of the insulin-producing beta cells of the - ketosis pancreas. At clinical presentation, around 80–90 per cent of - rapid weight loss the beta cells will have been destroyed,4 consequently leading - BMI <25kg/m2 to hyperglycaemia. Patients typically present with one or more - age of onset <50 years of the classical symptoms caused by hyperglycaemia: polyuria, - personal or family history of autoimmune disease (new recommendation) polydipsia, lethargy and unexplained weight loss.5 People with T1DM are absolutely dependent on exogenous insulin ther- • Nevertheless, type 1 diabetes should not be ruled out in people >50 apy to prevent the development of ketosis and hyperglycae- years and with a BMI >25kg/m2 (new recommendation) mia, ultimately leading to diabetic ketoacidosis if untreated.5 The NICE guideline on management of T1DM in adults was • Anyone of any age or any BMI who presents with polyuria and updated in August 2015, providing specific recommendations polydipsia, especially those with weight loss and nausea, should have for diagnosis (see Table 2).6 their random glucose and blood/urinary ketones checked. Ketonuria or ketonaemia should raise suspicion of type 1 diabetes Type 2 diabetes mellitus In the UK, about 90 per cent of people with diabetes mellitus • Diabetic ketoacidosis (ketonaemia ≥3mmol/L or 2+ ketonuria on have T2DM, which results from inadequate insulin secretion test strip; venous bicarbonate <15mmol/L or venous pH <7.3; or a (beta cell dysfunction) and/or reduced action of insulin on insu- combination of them both) is a medical emergency lin-responsive cells (insulin resistance) leading to deranged glucose handling.7 A myriad of risk factors for T2DM have been • Lesser degrees of ketosis with hyperglycaemia (>11mmol/L) will identified (see Table 3).8 Factors such as ethnicity play a sig- probably also require urgent administration of insulin nificant role in determining those at high risk of T2DM with • Consider further investigation, eg measurement of C-peptide or its prevalence increasing four-fold in people of Bangladeshi diabetes-specific autoantibodies or both, if patient has atypical and Indian origin, and five-fold in women of Pakistani origin.9 features ie age >50 years, BMI>25kg/m2, slow evolution of There is good evidence linking obesity to T2DM associated with hyperglycaemia and if there is a degree of uncertainty about what the development of insulin resistance.9 Therefore, in terms of type of diabetes the patient has (new recommendation) management, encouraging improvement in lifestyle remains paramount in controlling T2DM. Table 2. Diagnosis of type 1 diabetes (in accordance with updated NICE guideline on type 1 diabetes in adults, published August 20156) General aims of management The principal aim of diabetes management is to restore blood lifestyle, co-morbidities and likelihood of developing complica- glucose to normal and thus reduce the incidence and progres- tions, but without causing problematic hypoglycaemia.6 sion of diabetes complications.10 Inadequately controlled blood There are three broad types of pharmaceutically produced glucose levels can cause both macrovascular and microvascu- insulin preparations available: lar damage, and subsequently lead to nephropathy, retinopathy, • Animal insulins: extracted and purified from cows (bovine) or neuropathy and cardiovascular diseases, all of which impact pigs (porcine) and now used by very few patients with diabetes profoundly on patients’ mortality, morbidity and quality of life.11 • Human insulin: genetically engineered with an identical amino Therefore, healthcare professionals aim to help people with acid sequence to endogenous human insulin diabetes to reach and maintain blood glucose control without • Insulin analogues: genetically engineered insulins with a sim- increasing the incidence of hypoglycaemia, which is the great- ilar but modified amino acid sequence to endogenous human est risk of insulin therapy. insulin and may be synthetically modified. Insulin therapy in T1DM Insulins can also be grouped by their onset and duration of Treatment with insulin remains essential for the management of action, as categorised in the BNF: T1DM4 (see Figure 1) via either subcutaneous injections or con- • Short-acting tinuous subcutaneous insulin infusion (CSII) using a pump worn • Intermediate and long-acting. 24 hours per day. The aim of exogenous insulin is to mimic as closely as possible the insulin profile of a person without dia- Short-acting insulins betes;12 however, the main barrier to achieving optimal blood Short-acting insulins are used principally to control the rise glucose control remains the risk of hypoglycaemia. The principal in blood glucose that occurs following ingestion of carbohy- methods for assessing blood glucose control are measurement drate, usually in a meal, and can be subdivided into soluble of glycated haemoglobin (HbA1c) and self-monitoring of cap- short-acting (human insulins) and rapid-acting (analogues of illary blood glucose (SMBG).6 In the NICE guideline, updated human insulin).12 in August 2015, the target HbA1c for people with T1DM is Human and animal insulins given by subcutaneous injection ≤48mmol/mol6 (normal range <42mmol/mol), alongside indi- have an onset of action of about 30 minutes with a peak of vidualisation of the target based on patients’ daily activities, action of between two and four hours and a duration of around prescriber.co.uk Prescriber September 2016 ❚ 51 ■ DRUG REVIEW l Insulin • People of south east Asian (particularly Pakistani and Intermediate and long-acting insulin Bangladeshi) descent People with T1DM usually take either an intermediate or • Overweight/obesity long-acting insulin in addition to their mealtime doses of rap- id-acting insulin analogues;6,12 the so-called basal part of the • Older age basal-bolus regimen. These insulins are administered in an • Family history of diabetes attempt to mimic the background secretion of insulin from the Gestational diabetes • pancreas in the interprandial or fasting period. In the 2015 • Polycystic ovary syndrome NICE guideline on T1DM in adults, it is recommended that insu- • Dyslipidaemia lin detemir (Levemir) is used twice daily as the basal insulin of • Sedentary lifestyle first choice alongside a rapid-acting insulin analogue.6 Insulin detemir is an analogue insulin in which a fatty acid moiety12 has Table 3. Risk factors for type 2 diabetes been bound to the lysine molecule at the B29 amino acid posi- eight hours.10 Due to their relatively slow onset of action com- tion resulting in it binding to albumin after injection. This results bined with the slow decline in insulin at the injection site, there in a prolonged duration of action and a relatively flat action pro- can be poor matching with the postprandial rise in blood glu- file without much of a peak.12 Insulin glargine (Lantus), another cose leading to a risk of hyperglycaemia and/or hypoglycaemia.13 long-acting insulin analogue, can be used as an alternative but Animal insulins are also much slower in action than comparable is usually administered once daily6 due to its longer duration of human insulins due to the increased development of antibodies action compared with insulin detemir.15 targeted against the animal insulin and are now rarely used. Long-acting insulin analogues are now preferred over the Rapid-acting insulin analogues were designed to resolve the intermediate-acting isophane insulins because their mode of slow onset of subcutaneously administered human insulin and action is more predictable.
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