Case study: Lean adult with no complications, newly diagnosed with type 2 diabetes

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1 Case study: Lean adult with no complications, newly diagnosed with type 2 diabetes Authored by Clifford Bailey and James LaSalle 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.

2 This case study outlines the treatment of an adult patient of lean build with newly diagnosed type 2 diabetes The case reflects a 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.

3 Lean adult with no complications, newly diagnosed with type 2 diabetes Simone, 53 years old, married, 2 healthy adult offspring School teacher, keeps fit by walking and gardening Cigarette smoker for 10 years (now quit), drinks 1 glass of wine/day Weight stable, diet generally good Recent bouts of lethargy and thirst, coinciding with need to urinate frequently during the day/night Also noticed desire to eat chocolate/ sugary snacks 53 years old Polyuria/nocturia Polydipsia Weight: 56.8 kg (125.2 lbs) Height: 152 cm (4 ft 12 in) BMI: 24.6 kg/m 2 BMI, body mass index

4 53 years old Weight: 56.8 kg (125.2 lbs) Height: 152 cm (4 ft 12 in) BMI: 24.6 kg/m 2 Polyuria/nocturia Polydipsia Former smoker Moderately active Simone describes her symptoms to the doctor Medical history and a blood sample are taken, blood pressure recorded Clinical chemistry FPG: 14.4 mmol/l HbA 1c : 8.3% Ketone body: Negative Anti-GAD antibody: Negative C-peptide: 0.5 nmol/l LDL cholesterol: 2.03 mmol/l HDL cholesterol: 2.11 mmol/l Triglycerides: 1.52 mmol/l Blood pressure* Systolic/diastolic: 138/88 mmhg Medical history No major illness No medication No familial diabetes Father died following stroke aged 71 Mother alive Click here to change units Click here to show normal range *Confirmed on subsequent visits Anti-GAD, glutamic acid decarboxylase; BMI, body mass index; FPG, fasting plasma glucose; HbA 1c, glycosylated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein

5 53 years old Weight: 56.8 kg (125.2 lbs) Height: 152 cm (4 ft 12 in) BMI: 24.6 kg/m 2 Polyuria/nocturia Polydipsia Former smoker Moderately active Simone describes her symptoms to the doctor Medical history and blood sample taken, blood pressure recorded Clinical chemistry Normal range FPG: 14.4 mmol/l mmol/l HbA 1c : 8.3% % Ketone body: Negative Negative Anti-GAD antibody: Negative Negative C-peptide: 0.5 nmol/l nmol/l LDL cholesterol: 2.03 mmol/l <2.6 mmol/l HDL cholesterol: 2.11 mmol/l >1.5 mmol/l Triglycerides: 1.52 mmol/l <1.7 mmol/l Blood pressure* Systolic/diastolic: 138/88 mmhg <120/80 mmhg Medical history No major illness No medication No familial diabetes Father died following stroke aged 71 Mother alive Click here to change units Click here to hide normal range *Confirmed on subsequent visits Anti-GAD, glutamic acid decarboxylase; BMI, body mass index; FPG, fasting plasma glucose; HbA 1c, glycosylated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein

6 53 years old Weight: 56.8 kg (125.2 lbs) Height: 152 cm (4 ft 12 in) BMI: 24.6 kg/m 2 Polyuria/nocturia Polydipsia Former smoker Moderately active Simone describes her symptoms to the doctor Medical history and blood sample taken, blood pressure recorded Clinical chemistry FPG: HbA 1c : Ketone body: Anti-GAD antibody: C-peptide: LDL cholesterol: HDL cholesterol: Triglycerides: Blood pressure* Systolic/diastolic: 259 mg/dl 67 mmol/mol Negative Negative 1.5 ng/ml 79 mg/dl 82 mg/dl 135 mg/dl 138/88 mmhg Medical history No major illness No medication No familial diabetes Father died following stroke aged 71 Mother alive Click here to change units Click here to show normal range *Confirmed on subsequent visits Anti-GAD, glutamic acid decarboxylase; BMI, body mass index; FPG, fasting plasma glucose; HbA 1c, glycosylated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein

7 53 years old Weight: 56.8 kg (125.2 lbs) Height: 152 cm (4 ft 12 in) BMI: 24.6 kg/m 2 Polyuria/nocturia Polydipsia Former smoker Moderately active Simone describes her symptoms to the doctor Medical history and blood sample taken, blood pressure recorded Clinical chemistry Normal range FPG: 259 mg/dl mg/dl HbA 1c : 67 mmol/mol mmol/mol Ketone body: Negative Negative Anti-GAD antibody: Negative Negative C-peptide: 1.5 ng/ml ng/ml LDL cholesterol: 79 mg/dl <100 mg/dl HDL cholesterol: 82 mg/dl >60 mg/dl Triglycerides: 135 mg/dl <150 mg/dl Blood pressure* Systolic/diastolic: 138/88 mmhg <120/80 mmhg Medical history No major illness No medication No familial diabetes Father died following stroke aged 71 Mother alive Click here to change units Click here to hide normal range *Confirmed on subsequent visits Anti-GAD, glutamic acid decarboxylase; BMI, body mass index; FPG, fasting plasma glucose; HbA 1c, glycosylated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein

8 A comprehensive approach to diabetes management An FPG of 14.4 mmol/l and HbA 1c of 8.3% (67 mmol/mol) show that Simone has type 2 diabetes Establishing glycaemic control is a priority for all newly diagnosed individuals. However, this should always be pursued within a multifactorial risk-reduction 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) With overt CVD (LDL cholesterol target <1.8 mmol/l; <70 mg/dl) 2,3 Who are aged >40 years with at least one additional CV risk factor Aspirin for secondary prevention of CVD or for those with high CV risk Baseline examinations to be performed in all newly diagnosed patients: Eye exam (refer to ophthalmologist): for signs of retinopathy Serum creatinine and 24 hour urine test: to assess kidney function Comprehensive foot exam: for signs of neuropathy Lifestyle interventions may be adequate to improve Simone s lipid profile and BP. If not, appropriate medications are indicated. ACE, angiotensin-converting enzyme; ACR, albumin:creatinine ratio; ARB, angiotensin II receptor blocker; BP, blood pressure; CV, cardiovascular; CVD, cardiovascular disease; DBP, diastolic blood pressure; FPG, fasting plasma glucose; HbA 1c, glycosylated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; SBP, systolic blood pressure. 1. Inzucchi SE et al. Diabetes Care 2012;35: American Diabetes Association. Diabetes Care 2013;36:S11 S Ryden L et al. Eur Heart J 2007;28:

9 Management of hyperglycaemia Despite a generally healthy lifestyle and diet, Simone is recommended to see a specialist and in the first instance to begin a diet and exercise plan, and undertake a programme of structured diabetes education Question In addition to lifestyle and educational interventions, which of the following is an appropriate option for Simone as antihyperglycaemic therapy? No additional therapy Metformin + DPP-4 inhibitor Basal insulin Metformin + sulphonylurea Metformin monotherapy Sulphonylurea monotherapy DPP-4, dipeptidyl peptidase 4

10 Treatment selected lifestyle adjustment plus: No additional therapy Maintaining a healthy lifestyle (including regular exercise and a balanced diet [or reduced caloric intake]) is essential to control weight and reduce the risk of CV complications 1 Intensive diet and exercise regimens can reduce weight and decrease the incidence of type 2 diabetes development 1,2 However, diet and exercise alone might not be sufficient to manage Simone s HbA 1c and could expose her to episodes of hyperglycaemia Increasing the risk of microvascular and macrovascular complications Clinical chemistry FPG: HbA 1c : 8.3%* Ketone body: Anti-GAD antibody: C-peptide: LDL cholesterol: HDL cholesterol: Triglycerides: Blood pressure Systolic/diastolic: 14.4 mmol/l Negative Negative 1.23 nmol/l 2.03 mmol/l 2.11 mmol/l 1.52 mmol/l 138/88 mmhg Anti-GAD, glutamic acid decarboxylase; CV, cardiovascular; FPG, fasting plasma glucose; HbA 1c, glycosylated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein. *(67 mmol/mol). 1. Pi-Sunyer X et al. Diabetes Care 2007;30: Knowler WC et al. N Engl J Med 2002;346: Please select another option:

11 Treatment selected lifestyle adjustment plus: Basal insulin In newly diagnosed individuals with HbA 1c >9.0%, temporary use of insulin is an effective therapy for lowering HbA 1c 1 Simone s HbA 1c is 8.3% (67 mmol/mol) Insulin 1,2 HbA 1c efficacy: Insulin therapy would be mandatory if ketonuria or other catabolic features of diabetes were present Major side effects: Cost: Low Simone was concerned about daily injections and wasn t comfortable with the possibility of hypoglycaemia High Hypoglycaemia risk: High Weight effect: Gain She was also concerned about potential weight gain and limitations on her ability to drive Her preference was for an alternative option and she asked about the possibility of oral treatments Hypoglycaemia HbA 1c, glycosylated haemoglobin. 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI / Inzucchi SE et al. Diabetes Care 2012;35: Please select another option:

12 Treatment selected lifestyle adjustment plus: Metformin + DPP-4 inhibitor At this stage the combination of metformin and a DPP-4 inhibitor is probably not necessary Although Simone has hyperglycaemia, a single oral antihyperglycaemic agent should be sufficient to reduce her HbA 1c to target In individuals with β-cell dysfunction, a therapy (or even an early combination of therapies) to support β-cell function may be required 1 Monitoring of HbA 1c every 3 months is recommended Both metformin and DPP-4 inhibitors are generally well tolerated with a low risk of hypoglycaemia Metformin 1,2 HbA 1c efficacy: High Hypoglycaemia risk: Low Weight effect: Major side effects: Cost: DPP-4 inhibitor 1,2 HbA 1c efficacy: Neutral/loss GI Lactic acidosis Low Hypoglycaemia risk: Low Weight effect: Major side effects: Cost: Intermediate Neutral Rare High DPP-4, dipeptidyl peptidase 4; GI, gastrointestinal; HbA 1c, glycosylated haemoglobin. 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI / Inzucchi SE et al. Diabetes Care 2012;35: Please select another option:

13 Treatment selected lifestyle adjustment plus: Metformin monotherapy Metformin monotherapy may be adequate therapy for Simone Metformin is only appropriate for those with adequate renal function Her hyperglycaemia at diagnosis was 8.3% (67 mmol/mol) and a single oral antihyperglycaemic agent might provide sufficient reductions in HbA 1c HbA 1c should be monitored every 3 months in people with newly diagnosed type 2 diabetes Metformin 1,2 HbA 1c efficacy: High Hypoglycaemia risk: Low Weight effect: Major side effects: Cost: Neutral/loss GI Lactic acidosis Low GI, gastrointestinal; HbA 1c, glycosylated haemoglobin. Combination therapy should be considered if target HbA 1c levels are not achieved within the 3 months In cases of β-cell dysfunction in newly diagnosed lean type 2 diabetes patients, an additional or alternative therapy that supports β-cell function may be appropriate 1 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI / Inzucchi SE et al. Diabetes Care 2012;35:

14 Treatment selected lifestyle adjustment plus: Sulphonylurea monotherapy Sulphonylurea (or a meglitinide, e.g. repaglinide) monotherapy may be adequate therapy for Simone Sulphonylurea 1,2 HbA 1c efficacy: Her HbA 1c at diagnosis was 8.3% Weight effect: (67 mmol/mol) and a single oral Major side effects: antihyperglycaemic agent might provide Cost: sufficient reductions in HbA 1c HbA 1c should be monitored every 3 months in people with newly diagnosed type 2 diabetes Combination therapy can be considered if target HbA 1c levels are not achieved within the 3 months High Hypoglycaemia risk: Moderate Gain Hypoglycaemia Low HbA 1c, glycosylated haemoglobin. In cases of β-cell dysfunction, an additional or alternative therapy that supports β-cell function may be appropriate 1 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI / Inzucchi SE et al. Diabetes Care 2012;35:

15 Treatment selected lifestyle adjustment plus: Metformin + sulphonylurea First-line therapy with metformin plus a sulphonylurea is probably not necessary A single oral antihyperglycaemic agent should be sufficient to reduce her HbA 1c to target The potential for β-cell dysfunction in lean people newly diagnosed with type 2 diabetes may require the use of particular therapy (or a combination of therapies) that supports β-cell function 1 Monitoring of HbA 1c every 3 months is recommended Sulphonylurea 1,2 HbA 1c efficacy: High Hypoglycaemia risk: Moderate Weight effect: Major side effects: Cost: Metformin 1,2 HbA 1c efficacy: Gain Hypoglycaemia Low High Hypoglycaemia risk: Low Weight effect: Major side effects: Cost: Neutral/loss GI Lactic acidosis Low GI, gastrointestinal; HbA 1c, glycosylated haemoglobin. 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI / Inzucchi SE et al. Diabetes Care 2012;35: Please select another option:

16 Treatment options for newly Emphasize healthy lifestyle diagnosed lean patients Tailor management plan to improve CV risk profile versus obese individuals Preference for agents not associated with hypoglycaemia or weight gain Sulphonylureas and meglitinides may be considered in suitable individuals Where appropriate opt for agents that support β-cell function Compared with their obese/ overweight counterparts: More marked degree of β-cell dysfunction 1,2 Insulin resistance generally lower 2 CVD risk factors less obvious Lower risk of macrovascular complications 1,3 In patients with HbA 1c >9% (75 mmol/mol), consider initiating insulin on a temporary basis or a combination of oral agents Increase glucose monitoring to reduce hypoglycaemia risk CV, cardiovascular; CVD, cardiovascular disease; HbA 1c, glycosylated haemoglobin. 1. Del Prato S et al. Int J Clin Pract 2010;64: Brunetti P. Int J Clin Pract Suppl 2007;153: Sinharoy K et al. J Indian Med Assoc 2008;106: Bailey CJ et al. Diab Vasc Dis Res 2013;DOI /

17 Target for glycaemic control Question Given the choice of therapy for Simone, what should be her target HbA 1c*? <6.0% % % % % 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; and 8.0% = 64 mmol/mol.

18 Target for glycaemic control* <6.0% % % % % Newly diagnosed lean people with type 2 diabetes who are not elderly or frail, should typically have an HbA 1c target of % 1 Treatment should aim to achieve this target safely and without causing hypoglycaemia 1 HbA 1c <7.0% is recommended for most people 1 However, treatment targets should be tailored to each individual 1 Targeting HbA 1c below 6.0% increases hypoglycaemia risk 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; and 8.0% = 64 mmol/mol. 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI /

19 Monitoring glycaemic control As part of therapy, Simone undergoes HbA 1c assessment every 3 6 months combined with SMBG initially on a daily basis SMBG provides an early indication of treatment effectiveness in lowering blood glucose At 3 months, if HbA 1c remains above target: Treatment review, with more intensive therapy (or a combination of therapies) considered ideally, this should involve agents that are not associated with an increased risk of hypoglycaemia Given potential for β-cell dysfunction, use of an agent or agents that support β-cell function is appropriate 1 HbA 1c, glycosylated haemoglobin; SMBG, self-monitoring of blood glucose 1. Bailey CJ et al. Diab Vasc Dis Res 2013;DOI /

20 Results of long-term follow-up Simone s polyuria, nocturia and polydipsia resolved, and her energy levels returned An oral antihyperglycaemic agent in combination with a controlled diet and exercise programme decreased her HbA 1c to 6.6% (49 mmol/mol) after 3 months Lifestyle interventions also improved Simone s blood pressure control and triglyceride levels Simone feels her quality of life has been restored Compared with obese/overweight patients: 1,2 Reduced susceptibility to macrovascular disease Fewer risk factors for CVD Primary focus for lean patients with type 2 diabetes is glycaemic control rather than multifactorial intervention 3 Simone s HbA 1c should be monitored on a 6-monthly or yearly basis CVD, cardiovascular disease; HbA 1c, glycosylated haemoglobin. 1. Brunetti P. Int J Clin Pract Suppl 2007;61: Sinharoy K et al. J Indian Med Assoc 2008;106: Del Prato S et al. Int J Clin Pract 2010;64:

21 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 mg/dl [ 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 /

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