Case study: Adult who is newly diagnosed with type 2 diabetes and at risk of hypoglycaemia

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Case study: Adult who is newly diagnosed with type 2 diabetes and at risk of hypoglycaemia Authored by Lawrence Leiter and Edward Horton on behalf of the Global Partnership for Effective Diabetes Management. The Global Partnership for Effective Diabetes Management is supported by an unrestricted educational grant from Bristol-Myers Squibb, AstraZeneca LP.

This case study outlines the treatment of an adult who is newly diagnosed with type 2 diabetes and at risk of hypoglycaemia The case reflects a full range of treatment and management tools available in the European/US context* *The management of any patient is subject to social, economic, gender, age, co-morbidity and ethnic variables, and is dependent on the range of treatment options available in specific regions or countries.

Adult who is newly diagnosed with type 2 diabetes and at risk of hypoglycaemia Jean is aged 75 and lives alone Recently, she has experienced episodes of extreme lethargy, thirst and an increased need to urinate Jean has severe arthritis in her hip and borderline osteopenia (managed via dietary modification) Jean s daughter encourages her to visit the doctor for a check-up

First visit with the doctor Jean outlines her symptoms to the doctor who tells her she has put on 3 kg in 6 months Jean says she finds it difficult to stand long enough to prepare regular, healthy meals and she usually snacks on ready-made meals She explains that both the tiredness and arthritis make exercise almost impossible Clinical chemistry FPG: 10.5 mmol/l HbA 1c : 8.7% LDL-cholesterol: 2.8 mmol/l HDL-cholesterol: 1.2 mmol/l Triglycerides: 1.3 mmol/l egfr: 93 ml/min Blood pressure* Systolic/diastolic: 150/89 mmhg BMI: 25.5 kg/m 2 Click here to change units Click here to show normal range Additional testing for ketone body, anti-gad antibody and C-peptide may be performed subject to regional variation and patient presentation. *Confirmed on subsequent visits. BMI, body mass index; FPG, fasting plasma glucose; GAD, glutamic acid decarboxylase; HbA 1c, glycosylated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; egfr, estimated glomerular filtration rate.

First visit with the doctor Jean outlines her symptoms to the doctor who tells her she has put on 3 kg in 6 months Jean says she finds it difficult to stand long enough to prepare regular, healthy meals and she usually snacks on ready-made meals She explains that both the tiredness and arthritis make exercise almost impossible Clinical chemistry Normal range FPG: 10.5 mmol/l 3.9 5.5 mmol/l HbA 1c : 8.7% 4.0 6.0% LDL-cholesterol: 2.8 mmol/l <2.6 mmol/l HDL-cholesterol: 1.2 mmol/l >1.5 mmol/l Triglycerides: 1.3 mmol/l <1.7 mmol/l egfr: 93 ml/min 90 120 ml/min Blood pressure* Systolic/diastolic: 150/89 mmhg 120/80 mmhg BMI: 25.5 kg/m 2 18.5 24.9 kg/m 2 Click here to change units Click here to hide normal range Additional testing for ketone body, anti-gad antibody and C-peptide may be performed subject to regional variation and patient presentation. *Confirmed on subsequent visits. BMI, body mass index; FPG, fasting plasma glucose; GAD, glutamic acid decarboxylase; HbA 1c, glycosylated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; egfr, estimated glomerular filtration rate.

First visit with the doctor Jean outlines her symptoms to the doctor who tells her she has put on 3 kg in 6 months Jean says she finds it difficult to stand long enough to prepare regular, healthy meals and she usually snacks on ready-made meals She explains that both the tiredness and arthritis make exercise almost impossible Clinical chemistry FPG: HbA 1c : LDL-cholesterol: HDL-cholesterol: Triglycerides: egfr: Blood pressure* Systolic/diastolic 189 mg/dl 72 mmol/mol 108 mg/dl 46 mg/dl 115 mg/dl 93 ml/min 150/89 mmhg BMI: 25.5 kg/m 2 Click here to change units Click here to show normal range Additional testing for ketone body, anti-gad antibody and C-peptide may be performed subject to regional variation and patient presentation. *Confirmed on subsequent visits. BMI, body mass index; FPG, fasting plasma glucose; GAD, glutamic acid decarboxylase; HbA 1c, glycosylated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; egfr, estimated glomerular filtration rate.

First visit with the doctor Jean outlines her symptoms to the doctor who tells her she has put on 3 kg in 6 months Jean says she finds it difficult to stand long enough to prepare regular, healthy meals and she usually snacks on ready-made meals She explains that both the tiredness and arthritis make exercise almost impossible Clinical chemistry Normal range FPG: 189 mg/dl 70 100 mg/dl HbA 1c : 72 mmol/mol 20 42 mmol/mol LDL-cholesterol: 108 mg/dl <100 mg/dl HDL-cholesterol: 46 mg/dl >60 mg/dl Triglycerides: 115 mg/dl <150 mg/dl egfr: 93 ml/min 90 120 ml/min Blood pressure* Systolic/diastolic: 150/89 mmhg 120/80 mmhg BMI: 25.5 kg/m 2 18.5 24.9 kg/m 2 Click here to change units Click here to hide normal range Additional testing for ketone body, anti-gad antibody and C-peptide may be performed subject to regional variation and patient presentation. *Confirmed on subsequent visits. BMI, body mass index; FPG, fasting plasma glucose; GAD, glutamic acid decarboxylase; HbA 1c, glycosylated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; egfr, estimated glomerular filtration rate.

A comprehensive approach to type 2 diabetes management Jean is diagnosed with type 2 diabetes. Establishing glycaemic control is a priority for all newly diagnosed individuals, but should be pursued within a multifactorial riskreduction framework that includes appropriate lifestyle interventions 1 In addition to antihyperglycaemic medication, consider the following for all people newly diagnosed with type 2 diabetes: 2 ACE inhibitors/arbs (or alternative if contraindications exist) if SBP 140 mmhg, DBP >80 mmhg or if ACR is 2.5 mg/mmol ( 30 mg/g) Statin drugs for those: With LDL-cholesterol >2.6 mmol/l (>100 mg/dl) OR With overt CVD (LDL-cholesterol target <1.8 mmol/l; <70 mg/dl) 2,3 OR Who are aged >40 years with at least one additional CVD risk factor* ASA for secondary prevention of CVD or for those with high CV risk Baseline examinations to be performed in all people newly diagnosed with type 2 diabetes: Eye exam (refer to ophthalmologist): for signs of retinopathy Serum creatinine (to calculate egfr) and 24 hour urine test: to assess kidney function Comprehensive foot exam: for signs of neuropathy *Family history of CVD, hypertension, smoking, dyslipidaemia or albuminuria. 24 hour urine test may not always be required. ACR could also be obtained to assess kidney function. ACE, angiotensin-converting enzyme; ACR, albumin:creatinine ratio; ARB, angiotensin II receptor blocker; CVD, cardiovascular disease; DBP, diastolic blood pressure; egfr, estimated glomerular filtration rate; LDL, low-density lipoprotein; SBP, systolic blood pressure. 1. Inzucchi SE et al. Diabetes Care 2012;35:1364 1379. 2. American Diabetes Association. Diabetes Care 2013;36:S11 S66. 3. Ryden L et al. Eur Heart J 2007;28:88 136.

Setting a glycaemic target Jean is diagnosed with type 2 diabetes with a FPG of 10.5 mmol/l and an HbA 1c of 8.7% (72 mmol/mol) The doctor tells Jean that in addition to lifestyle interventions, it will be necessary to start medication to reduce her BG levels, and they discuss her glycaemic target Question What is the most appropriate HbA 1c * target for Jean? <6.0% 6.0 6.5% 6.5 7.0% 7.0 7.5% 7.5 8.0% BG, blood glucose; FPG, fasting plasma glucose; HbA 1c, glycosylated haemoglobin. *Equivalent values: 6.0% = 42 mmol/mol; 6.5% = 48 mmol/mol; 7.0% = 53 mmol/mol; 7.5% = 58 mmol/mol; 8.0% = 64 mmol/mol.

Setting a glycaemic target What is the most appropriate HbA 1c * target for Jean? <6.0% 6.0 6.5% 6.5 7.0% 7.0 7.5% 7.5 8.0% The recommended target for most people with type 2 diabetes is <7.0%; however, glycaemic targets should always be individualized The doctor is alerted to Jean s increased risk of hypoglycaemia, owing to: Older age: risk of hypoglycaemia increases exponentially with age Irregular eating pattern: increases risk, particularly when taking hypoglycaemic agents Lives alone: self-treating or seeking of medical attention may be significantly delayed Poor mobility: increases susceptibility to falls (a particular issue in Jean s case given her osteopenia) The glycaemic target for patients at risk of hypoglycaemia should be 7.0 7.5% or even up to 8.5% in patients at the highest risk, in the elderly or those who live alone 1 A glycaemic target of 7.0 7.5% is set. Jean will be monitored closely and the target reassessed if its attainment proves difficult or if safety becomes a concern HbA 1c, glycosylated haemoglobin. *Equivalent values: 7.0% = 53 mmol/mol; 7.5% = 58 mmol/mol; 8.0% = 64 mmol/mol; 8.5% = 69 mmol/mol. 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765.

Initial medication The doctor tells Jean that in addition to lifestyle interventions, she will require antihyperglycaemic medication to reduce and maintain her BG within the agreed target range Question In addition to lifestyle interventions, which of the following is appropriate firstline antihyperglycaemic medication for Jean? Metformin Basal insulin Metformin + sulphonylurea Metformin + DPP- 4 inhibitor Sulphonylurea BG, blood glucose; DPP, dipeptidyl peptidase.

Initial medication In addition to lifestyle interventions, which of the following is appropriate firstline antihyperglycaemic medication for Jean? Metformin Basal insulin Metformin + sulphonylurea Metformin + DPP- 4 inhibitor Sulphonylurea Unless contraindicated, metformin is the first-line agent of choice for most people with type 2 diabetes: 1 metformin would not be appropriate if renal insufficiency was present, a common co-morbidity in elderly individuals Metformin carries a low risk of hypoglycaemia, is weight neutral and lowers HbA 1c by an average of 1 2% 1,2 Initial therapy with a combination of drugs or insulin should be reserved for those presenting with a high HbA 1c (e.g. 9.0%; 75 mmol/mol) 1 HbA 1c, glycosylated haemoglobin. 1. Inzucchi SE et al. Diabetes Care 2012;35:1364 1379. 2. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765.

Further instructions and additional medication As metformin can cause GI symptoms, 1 the doctor recommends a gradual upwards titration of metformin beginning with 500 mg bid and titrating to 850 mg b.i.d after 4 weeks Jean was advised to always take the medication with meals/food In addition to medications for her hyperglycaemia, Jean was prescribed an ARB to reduce her BP and a statin to lower her LDL-cholesterol She was also referred to a diabetes education centre to develop a diet and exercise plan and learn about self monitoring of blood glucose A 3-month follow-up appointment was then made for Jean Metformin 1,2 HbA 1c efficacy: High Hypoglycaemia risk: Low Weight effect: Major side effects: Cost: Neutral/loss GI Lactic acidosis Low ARB, angiotensin receptor blocker; b.i.d., twice daily; BP, blood pressure; GI, gastrointestinal; HbA 1c, glycosylated haemoglobin. 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765. 2. Inzucchi SE et al. Diabetes Care 2012;35:1364 1379.

BG, blood glucose; BMI, body mass index; BP, blood pressure; FPG, fasting plasma glucose; HbA 1c, glycosylated haemoglobin. 3-month follow-up appointment: BG and BP target levels not achieved Jean reports that, apart from an occasional stomach upset, she feels well She has been trying to eat more regularly and has lost a small amount of weight Jean also reports good adherence to her medication and is able to explain her regimen to the doctor Despite these factors, however, Jean s BG and BP remain above their targets Current status/assessments FPG: 9.0 mmol/l (162 mg/dl) HbA 1c : 8.1% (66 mmol/mol) BP: 142/86 mmhg BMI: 25.0 kg/m 2 Question Which is the most appropriate next course of action for Jean in response to inadequate glycaemic and BP control? Re-assess in a further 3 months to see whether the problem persists Intensify antihyperglycaemic and antihypertensive medications Re-assess factors other than medication that might result in failure to respond

Response to not achieving targets: Re-assess in 3 months The benefit : risk ratio must always be considered when designing individualized treatment regimens Although a less-intensive approach to glycaemic control is appropriate for Jean (given her increased hypoglycaemia risk), the combination of hyperglycaemia and hypertension increases her risk of vascular complications Measures should be taken immediately to minimize this risk Opting for a sensible combination of antihyperglycaemic medications will help to ensure that intensification of therapy improves glycaemia without enhancing the risk of hypoglycaemia Please select another option

Response to not achieving targets: Immediately intensify treatment The combination of hyperglycaemia and hypertension increases the risk of vascular complications, and measures should be taken to limit this risk It is important to explore all possible reasons for the lack of glycaemic and BP control Jean reports improved dietary habits and good adherence to medication, suggesting that lifestyle factors/poor adherence do not contribute to the lack of glycaemic and BP control People with type 2 diabetes often require combination therapy to meet glycaemic and BP targets Opting for a sensible combination of antihyperglycaemic medications will help to ensure that intensification of therapy improves glycaemia without enhancing the risk of hypoglycaemia BP, blood pressure.

Response to not achieving targets: Re-assess factors other than medication The combination of hyperglycaemia and hypertension increases the risk of vascular complications Exploring all the possible factors behind lack of glycaemic and BP control is important; re-assessing lifestyle factors/adherence issues alone is not sufficient to minimize this risk Jean reports improved dietary habits and good adherence to medication, suggesting that lifestyle factors/poor adherence do not contribute to the lack of glycaemic and BP control People with type 2 diabetes often require combination therapy to meet glycaemic and BP targets Opting for a sensible combination of antihyperglycaemic medications will help to ensure that intensification of therapy improves glycaemia without enhancing the risk of hypoglycaemia BP, blood pressure.

Selection of second-line antihyperglycaemic therapy Jean s medication requires intensifying and as part of this, the doctor increases the dose of antihypertensive medication As Jean has already reported some GI symptoms with her current dose of metformin, the doctor decides to combine metformin with another agent, and to reduce the metformin dose to 500 mg b.i.d Question In addition to lifestyle interventions, which of the following is an appropriate combination of antihyperglycaemic medication for Jean? Metformin + sulphonylurea Metformin + basal insulin Metformin + DPP-4 inhibitor Metformin + thiazolidinedione Metformin + GLP-1 receptor agonist b.i.d, twice daily; DPP, dipeptidyl peptidase; GI, gastrointestinal; GLP, glucagon-like peptide.

Second-line therapy chosen (alongside lifestyle interventions): Metformin + sulphonylurea Sulphonylureas can lower BG rapidly and carry a moderate risk of hypoglycaemia 1 Although not contraindicated in those at risk of hypoglycaemia, sulphonylureas should be used with caution in this patient population To reduce the risk of hypoglycaemia, incretin agents can be used before secretagogues As Jean does not require a large reduction in HbA 1c, an alternative combination that lowers HbA 1c with a lower risk of hypoglycaemia may be more appropriate Sulfonylureas may also cause weight gain and due to her immobility, Jean is reluctant to use this medication BG, blood glucose; GI, gastrointestinal; HbA 1c, glycosylated haemoglobin. 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765. 2. Inzucchi SE et al. Diabetes Care 2012;35:1364 1379. Metformin 1,2 HbA 1c efficacy: Sulphonylurea 1,2 HbA 1c efficacy: High Hypoglycaemia risk: Moderate Weight effect: Major side effects: Cost: High Hypoglycaemia risk: Low Weight effect: Major side effects: Cost: Neutral/loss GI Lactic acidosis Low Gain Hypoglycaemia Low Please select another option

HbA 1c (%) % of patients Second-line therapy chosen (alongside lifestyle interventions): Metformin + DPP-4 inhibitor DPP-4 inhibitors reduce BG levels to a similar extent as sulphonylureas and have a lower risk of hypoglycaemia 1 DPP-4 inhibitors are well tolerated and do not cause weight gain; Jean is relatively immobile and therefore susceptible to gaining weight Many of the DPP-4 inhibitors can be taken once daily, minimizing the risk of nonadherence due to complicated medication regimens The doctor and Jean decide on a combination of metformin and a DPP-4 inhibitor as the most appropriate for Jean s individual circumstances A. 7.6 HbA 1C Hypoglycaemic episodes B. 35 Metformin + * 7.4 glipizide 30 25 7.2 Metformin + sitagliptin 20 7 15 6.8 10 6.6 5 6.4 Week 1 Week 52 1. Nauck MA et al. Diabetes Obese Metab 2007;9:194 205. 0 Metformin + Glipizide Metformin + Sitagliptin Patients with hyperglycaemia despite metformin therapy were randomized to receive either sitagliptin or glipizide as add-on therapy. 1 By week 52; *p<0.001 compared with metformin + sitagliptin. BG, blood glucose; DPP, dipeptidyl peptidase HbA 1c, glycosylated haemoglobin.

Second-line therapy chosen (alongside lifestyle interventions): Metformin + basal insulin Insulin lowers BG rapidly and carries a high risk of hypoglycaemia 1 Although not contraindicated in those at risk of hypoglycaemia, a less intensive approach to lowering HbA 1c should be taken in this patient population Insulin therapy is generally recommended for patients with more marked hyperglycaemia (HbA 1c >9%; 75 mmol/mol), or when dual therapy is insufficient at achieving glycaemic control 1 In addition, insulin requires good motor skills and can be particularly difficult for elderly patients to administer; insulin can also cause weight gain Metformin 1,2 HbA 1c efficacy: Hypoglycaemia risk: Weight effect: Major side effects: Insulin may be considered for Jean if glycaemic control is not achieved with oral agents or if glycaemic control worsens over time Cost: Low A pre-mixed insulin preparation is often preferred for elderly patients if bedtime basal insulin is insufficient, as this can minimize dosing errors Cost: Insulin 1,2 HbA 1c efficacy: Hypoglycaemia risk: Weight effect: Major side effects: High Low Neutral/loss GI Lactic acidosis Low High High Gain Hypoglycaemia BG, blood glucose; GI, gastrointestinal; HbA 1c, glycosylated haemoglobin. 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765. 2. Inzucchi SE et al. Diabetes Care 2012;35:1364 1379. Please select another option

% of fractures Second-line therapy chosen (alongside lifestyle interventions): Metformin + thiazolidinedione Thiazolidinediones carry a low risk of hypoglycaemia However, they are associated with increased risk of heart failure and higher numbers of bone fractures, 1 particularly in women It is important to minimize the likelihood of CV events in patients at risk of hypoglycaemia The increased risk of bone fractures is also not optimal; Jean is elderly with severe arthritis in her hip and diagnosed osteopenia Thiazolidinediones may also cause weight gain The doctor and Jean decide that this is not the best option for her personal circumstances Increased incidence of bone fractures in women taking thiazolidinediones 1 10 Men 9 Women 8 7 6 5 4 * * 3 2 1 0 *p<0.01 compared with thiazolidinedione CV, cardiovascular. 1. Kahn SE et al. N Eng J Med 2006;355:2427 2443. Please select another option

Second-line therapy chosen (alongside lifestyle interventions): Metformin + GLP-1 receptor agonist GLP-1 receptor agonists carry a risk of hypoglycaemia when combined with other antihyperglycaemic agents 1 An advantage with these agents is weight loss; Jean is borderline overweight and fairly immobile, making weight loss difficult However, these agents are injectable, and common side-effects include nausea and vomiting 1 After discussing her options, the doctor and Jean decide that this is not the most appropriate combination for her individual circumstances Metformin 1,2 HbA 1c efficacy: GLP-1 receptor agonist 1,2 HbA 1c efficacy: High Hypoglycaemia risk: Low Weight effect: Major side effects: Cost: High Hypoglycaemia risk: Low Weight effect: Major side effects: Cost: Neutral/loss GI Lactic acidosis Low Neutral/loss GI Moderate GI, gastrointestinal; GLP, glucagon-like peptide; HbA 1c, glycosylated haemoglobin. 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765. 2. Inzucchi SE et al. Diabetes Care 2012;35:1364 1379. Please select another option

Patients (%) Patients with 1 HE (%) Why is hypoglycaemia an important In patients with type 2 diabetes: consideration? Hypoglycaemic events (HE) have been shown to increase risk for acute cardiovascular events (ACVE) 1 A strong association between severe hypoglycaemia (SH) and adverse clinical outcomes has been demonstrated 2 Hypoglycaemia is associated with increased risk of acute CV events 1 6 * 5 1 HE 4 3 2 1 0 Any ACVE No HE Inpatient death from ACVE *p<0.001 compared with patients with no HE * 25 20 15 10 5 0 Severe hypoglycaemia is associated with increased risk of adverse clinical events 2 * Major macrovascular event Major microvascular event *p<0.001 compared with patients with no SH * * Death from any cause SH No SH a See slide 35 in deck for copyright acknowledgement. 1. Johnston SS et al. Diabetes Care 2011;34:1164 1170. 2. Zoungas S et al. N Engl J Med 2010;363:1410 1418.

Why is hypoglycaemia an important consideration? In addition to serious CV and other health outcomes, hypoglycaemia can have a negative impact on several aspects of an individual s life Question Which of the following are associated with mild hypoglycaemia? Anxiety Click for info Poor adherence to medication Click for info Reduced independence Click for info Time away from work Click for info CV, cardiovascular.

Why is hypoglycaemia an important consideration? Anxiety Click to hide Those who experience hypoglycaemia often report feelings of anxiety. 1 Not only does this impact on an individual s well being, but stress may also be a cause of hypoglycaemia 1 1. Brod M et al. Value Health 2011;14:665 671.

Why is hypoglycaemia an important consideration? Poor adherence to medication Click to hide Those who experience hypoglycaemia may become reluctant to take their medication, 1 exposing patients to the consequences of poor glycaemic control 1. Brod M et al. Value Health 2011;14:665 671.

Why is hypoglycaemia an important consideration? Hypoglycaemia can have a significant impact on an individual s quality of life, since normal day-to-day activities such as driving may need to be restricted 1 Reduced independence Click to hide 1. Brod M et al. Value Health 2011;14:665 671.

Why is hypoglycaemia an important consideration? Even mild hypoglycaemic events occurring at, or outside of, work lead to a significant number of hours away from the workplace 1 Time away from work Click to hide 1. Brod M et al. Value Health 2011;14:665 671.

Awareness of hypoglycaemia and how to treat Jean s medication was selected to minimize her risk of hypoglycaemia However, elderly patients with diabetes often fail to recognize the symptoms of hypoglycaemia 1 and this is something Jean needs to learn as part of managing her condition Show symptoms of hypoglycaemia Question If Jean becomes hypoglycaemic/experiences hypoglycaemic symptoms and is able to self treat, what should she be advised to do? Ingest 15 g of glucose/sucrose then call the emergency services Ingest 15 g of glucose/sucrose, wait 15 minutes then take another 15 g glucose/sucrose if BG is <4.0 mmol/l; once hypoglycaemia is reversed have a meal or snack to prevent recurrence Administer 1 mg glucagon intramuscularly or subcutaneously; once hypoglycaemia is reversed have a meal or snack to prevent recurrence BG, blood glucose. 1. Bremer JP et al. Diabetes Care. 2009;32:1513-1517.

Awareness of hypoglycaemia and how to treat Jean s medication was selected to minimize her risk of hypoglycaemia However, elderly patients with diabetes often fail to recognize the symptoms of hypoglycaemia 1 and this is something Jean needs to learn as part of managing her condition Hide symptoms of hypoglycaemia Question If Symptoms Jean becomes of hypoglycaemia hypoglycaemic/experiences hypoglycaemic symptoms and is able to Neurogenic self treat, (autonomic) what should she be advised Neuroglycopenic to do? Trembling Palpitations Sweating Ingest 15 g of glucose/sucrose then call the emergency services Ingest 15 g of glucose/sucrose, wait 15 minutes then take another 15 g glucose/sucrose if Anxiety BG is <4.0 mmol/l; once hypoglycaemia is reversed have a meal or snack to prevent recurrence Hunger Nausea Difficulty concentrating Confusion Weakness Drowsiness Vision changes Difficulty speaking Administer 1 mg glucagon intramuscularly or subcutaneously; once hypoglycaemia is Tingling reversed have a meal or snack to prevent Headache recurrence Dizziness 1. Bremer JP et al. Diabetes Care. 2009;32:1513-1517.

Awareness of hypoglycaemia and how to treat Question If Jean becomes hypoglycaemic/experiences symptoms and feels able to self treat, what should she be advised to do? Ingest 15 g of glucose/sucrose, wait 15 minutes then take another 15 g glucose/sucrose if BG is <4.0 mmol/l; once hypoglycaemia is reversed have a meal or snack to prevent recurrence Show examples of 15 g glucose/sucrose Ingestion of 15 g glucose raises BG levels by approx. 2.1 mmol/l within 20 minutes In cases of severe hypoglycaemia, where a person requires assistance to treat, 20 g of glucose/sucrose should be given in the first instance to a conscious person 1,2 Glucagon should be administered by a friend or caregiver in the case of severe hypoglycaemia with unconsciousness; the emergency services should also be called 1,2 Even if Jean feels able to self treat, it is good practice for Jean to inform somebody who lives nearby that she is feeling unwell, so they can check for full recovery A family member, friend or caregiver who lives nearby should be trained in treating hypoglycaemia, so that Jean can be assisted if necessary BG, blood glucose. 1. Canadian Diabetes Association. Can J Diabetes 2008;32:S20:S201. 2. American Diabetes Association. Diabetes Care 2013;36:S11 S66.

Awareness of hypoglycaemia and how to treat Question If Jean becomes hypoglycaemic/experiences symptoms and feels able to self treat, what should she be advised to do? Ingest 15 g of glucose/sucrose, wait 15 minutes then take another 15 g glucose/sucrose if BG is <4.0 mmol/l; once hypoglycaemia is reversed have a meal or snack to prevent recurrence Hide examples of 15 g glucose/sucrose Examples of 15 g of glucose/sucrose for treatment of mild to moderate hypoglycaemia Ingestion of 15 g glucose raises BG levels by approx. 2.1 mmol/l within 20 minutes In cases of severe hypoglycaemia, where a person requires assistance to treat, 20 g of 15 g of glucose in the form of glucose tablets glucose/sucrose should be given in the first instance to a conscious person 1,2 15 ml (3 teaspoons) of table sugar dissolved in water Glucagon should be administered by a friend or caregiver in the case of severe hypoglycaemia 175 ml (3/4 with cup) unconsciousness; of juice or regular the emergency soft drink services should also be called 1,2 15 ml (1 tablespoon) of honey Even if Jean feels able to self treat, it is good practice for Jean to inform somebody who lives nearby that she is feeling unwell, so they can check for full recovery A family member, friend or caregiver who lives nearby should be trained in treating hypoglycaemia, so that Jean can be assisted if necessary 1. Canadian Diabetes Association. Can J Diabetes 2008;32:S20:S201. 2. American Diabetes Association. Diabetes Care 2013;36:S11 S66.

6-month follow-up since initial diagnosis 3 months after starting combination therapy (6 months since initial diagnosis), Jean s HbA 1c is within the target range Her BP is still above target, however, and the doctor adds a second antihypertensive (a CCB) to Jean s regimen Jean s therapy has not caused any weight gain The doctor stresses the importance of regular meals and adherence to medication Current assessments FPG: 4.4 mmol/l (80 mg/dl) HbA 1c : 7.2% (55 mmol/mol) BP: 135/85 mmhg BMI: 24.5 kg/m 2 BMI, body mass index; BP, blood pressure; CCB, calcium channel blocker; FPG, fasting plasma glucose; HbA 1c, glycosylated haemoglobin.

Permission statements/copyright acknowledgement a Slide 24 From New England Journal of Medicine, Sophia Zoungas, Anushka Patel, John Chalmers, et al. 363, Severe Hypoglycemia and Risks of Vascular Events and Death 1410-1418. Copyright 2010 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

10 Steps to get more type 2 diabetes patients to goal The Global Partnership for Effective Diabetes Management recommends: 1 10 Steps to get more people with type 2 diabetes to goal: Aim for an appropriate individualized glycaemic target, e.g. HbA 1c 6.5 7% (48 53 mmol/mol) (or fasting/preprandial plasma glucose 110 130 mg/dl [6.0 7.2 mmol/l] where assessment of HbA 1c is not possible) when safe and appropriate. Monitor HbA 1c every 3 months in addition to appropriate glucose self-monitoring. Appropriately manage all cardiovascular risk factors. Refer all newly diagnosed patients to a unit specializing in diabetes care where possible. Address the underlying pathophysiology of diabetes, including the treatment of β-cell dysfunction and insulin resistance. Treat to achieve appropriate target HbA 1c within 6 months of diagnosis. After 3 months, if patients are not at the desired target HbA 1c, consider combination therapy. Consider initiating combination therapy or insulin for patients with HbA 1c 9% ( 75 mmol/mol). Use combinations of antihyperglycaemic agents with complementary mechanisms of action. Implement a multidisciplinary team approach that encourages patient self-management, education and self-care, with shared responsibilities to achieve goals. HbA 1c, glycosylated haemoglobin. 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI 10.1177/1479164113490765.

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