Diabetes Clinical update There have been important changes in diabetes care which may not be covered in undergraduate textbooks. Changes in the diagnosis of diabetes a) HbA1C Since 2011, World Health Organisation (WHO) has included the use of glycated haemoglobin (HbA1C) in diagnosis of diabetes mellitus. This does not replace existing diagnostic criteria based on plasma glucose, but has the advantage of not requiring patient to fast. HbA1C 48 mmol/mol (6.5%) is taken as cut-off, but several caveats need to be taken into account in interpretation of result: Result is from laboratory assay validated by national assurance schemes (HbA1C done using capillary blood from point-of-care testing machines may not always fulfil this standard). Similar to glucose testing, HbA1C requires repeating if patient is asymptomatic. If the second sample is <48 mmol/mol, then the patient is treated as at high risk of diabetes, with lifestyle advice, and HbA1C is repeated at 6 months. The corollary is that HbA1C < 48 mmol/mol may not exclude diabetes in these situations, and glucose testing should be used instead. Where diagnosis is already reached using plasma glucose testing ALL children and young people patients of any age suspected of having Type 1 diabetes patients with symptoms of diabetes for less than 2 months patients at high risk who are acutely ill (e.g. those requiring hospital admission) patients taking medication that may cause rapid glucose rise e.g. steroids, antipsychotics patients with acute pancreatic damage, including pancreatic surgery in pregnancy Presence of genetic, haematologic and illness-related factors that influence HbA1c and its measurement (eg disorders of erythropoiesis, haemolysis, chronic renal failure, chronic liver disease). 1 Diabetes
b) OGTT in pregnancy In the particular case of pregnancy, the 75g anhydrous glucose in an oral glucose tolerance test (OGTT) is used. The cut-offs are different compared to those outside pregnancy setting. Gestational diabetes is diagnosed if the patient has either: Fasting plasma glucose 5.6 mmol 2 hour plasma glucose 7.8 mmol 2 Diabetes
GLP-1 based therapies and SGLT2 inhibitors These are newer classes of diabetic drugs for use in type 2 diabetes. a) GLP-1 based therapies Incretins are hormones secreted by the gut in response to nutrient ingestion. Glucagon-like peptide 1 (GLP-1) is an incretin which stimulates insulin release, suppresses glucagon, inhibits gastric emptying and promotes satiety. These actions are mimicked by GLP-1 analogues that are resistant to degradation by the enzyme dipeptidyl peptidase-4 (DPP-4). Levels of endogenous GLP-1 can also be increased by DPP-4 inhibitors. GLP-1 analogues are given as subcutaneous injections. Examples are: Exenatide (twice daily), Liraglutide (once daily), Lixisenatide (once daily), Dulaglutide (once weekly). DPP-4 inhibitors are taken by mouth. Examples are: Sitagliptin, Alogliptin, Linagliptin, Vildagliptin. GLP-1 based treatments have the advantage of improving HbA1C by 0.5-1% without significant increase in hypoglycaemia. GLP-1 analogues may also promote weight loss. These drugs however do carry risk of gastrointestinal side effects (nausea and vomiting). With the exception of linagliptin, all other GLP-1 based treatments are excreted by kidneys should be used with caution in patients with renal impairment. In 2015 NICE guidance on management of type 2 diabetes, DPP-4 inhibitors have recommended usage as 1 st line drug in patients where metformin is contraindicated or not tolerated. Otherwise, it is an option for patients requiring intensification after metformin. GLP-1 analogues, in combination with sulphonylurea and metformin, can be offered to patients with: Obese patients with BMI > 35 (lower cut-offs for other ethnic groups) Where weight loss would benefit obesity related comorbidities (eg hypertension, hyperlipidaemia, osteoarthritis, sleep apnoea, PCOS). Where insulin treatment would lead to occupational restrictions (such as HGV drivers). b) SGLT2 inhibitors Sodium-glucose co-transporters type 2 (SGLT2) are localised to the renal proximal tubule and regulate glucose reabsorption from the glomerular filtrate. SGLT2 inhibitors therefore promote glucose excretion. These drugs can reduce HbA1C by 0.5%, without increasing hypoglycaemia, and can promote weight loss of up to 3-5 kg. Examples include: 3 Diabetes
Dapagliflozin, Canagliflozin and Empagliflozin. Side effects include thirst, polyuria, hypovolaemia, hypotension and increased incidence of genital and urinary infections. It is stopped in patients whose egfr falls below 45-50 ml/min/1.73 m 2. There have been case reports associating SGLT2 inhibitors with diabetic ketoacidosis, where presenting glucose levels have been only moderately raised. Following on, MHRA has issued a safety warning as of April 2016, alerting clinicians to inform patients of the signs and symptoms of diabetic ketoacidosis; drug is stopped with these are present. Also, SGLT2 inhibitors should be withheld temporarily in acute major illness and in those hospitalised for major surgery, until full recovery. 4 Diabetes
Safe insulin prescribing Medication errors involving insulin are common and are avoidable. A complete insulin prescription includes name of insulin, dose in units, injection device and time of administration. The word units cannot be abbreviated. When insulin is required to be drawn from a vial, only U100 insulin syringes can be used. It would be unusual for patients to have their regular insulin withheld at drug rounds. In patients who are fasted or receiving variable or fixed rate insulin infusion, basal insulin is continued, although short-acting insulin analogues are suspended. Patients who had suffered hypoglycaemia should continue with scheduled insulin once resuscitated to blood glucose level of > 4mmol, although the dose may require reduction. The names of different insulins can be confusing. When translating between drug charts, summary care records or insulin passports, extra care is required especially with these brands. Novorapid Novomix 30 Humalog Humalog mix25 Humalog mix50 Lantus Toujeo Abasaglar Insuman Comb 25 Insuman Comb 50 Degludec u100 Degludec u200 Xultophy Insulin analogue Pre-mixed biphasic insulin (30% novorapid, 70% intermediateacting isophane) Insulin analogue Pre-mixed biphasic insulin (25% Humalog, 75% isophane) 50% Humalog, 50% isophane Basal insulin glargine at U100 strength (100 units/ml) Glargine at U300 strength (300 units/ml) Biosimilar glargine at u100 strength Biphasic insulins containing 25% or 50% of soluble insulin mixed with protamine insulin Basal insulin at U100 strength Basal insulin at U200 strength Mixture of Degludec U100 and GLP-1 analogue liraglutide, delivered as dose steps (1 dose step = 1 unit of degludec U100 and 0.036mg liraglutide) Patients with type 1 diabetes who have received structured education routinely adjust prandial (fast-acting) insulin based on carbohydrate portion and prevailing capillary blood glucose. For example, a patient has mealtime ratio of 1 unit: 10g of carbohydrate and correction factor of 3 for readings above 8 mmol. If his pre-lunch reading is at 14 mmol and he intends to consume 100g of carbohydrate, he will proceed to self-administer 2 + 10 = total 12 units. 5 Diabetes
Assessing hypoglycaemia Hypoglycaemia is defined when patients have a blood glucose less than 4 mmol. At diabetes annual review, it is important to review (1) frequency, (2) triggers (3) timing and (4) symptoms patients experience when hypoglycaemic. Usual triggers of hypos include excess/ inappropriate insulin use, unplanned exercise, inadequate/ delayed meals, and alcohol use. Co-existing conditions such as renal failure, liver failure, adrenocortical insufficiency and gastroparesis should be considered. It is helpful to examine injection sites for lipodystrophy. Typical symptoms of hypoglycaemia are associated with sympathetic discharge and include feeling shaky, sweating, hunger, tiredness, blurred vision, lack of concentration, headaches, feeling tearful, stroppy or moody, going pale. For patients with type 1 diabetes, awareness can be assessed using the Gold score. Patients with longstanding insulin-treated diabetes and frequent hypos may have absent warning signs, even when blood glucose falls below 3 mmol. They are at risk of major hypo where because of predominant neuroglycopenia (confusion, reduced consciousness, seizure); third party help for resuscitation is required. For drivers, these episodes would require DVLA notification. Patients with frequent, unpredictable hypoglycaemia, nocturnal hypoglycaemia and have impaired hypo awareness should be referred for specialist review. In your hospital placement, you should observe treatment options available to these patients. 6 Diabetes