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T2DM diagnosis and management goals

Patient case study:

Diabetes is now estimated to have a global prevalence of 537 million.1

The majority of people living with T2DM have poor glycaemic control​. 52% have an HbA1c above 7% (53 mmol/mol).2

  • Poor glycaemic control leads to an increased risk of microvascular and macrovascular complications in people living with T2DM.3
  • For instance, diabetes is the most common cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), and therefore diabetic kidney disease is an important consideration for healthcare professionals supporting people living with type 2 diabetes.4

Dr. Amrit Lamba, GP, introduces Tom’s case

Presented here is a case study that explores metabolic syndrome, progression to type 2 diabetes, the concept of Time in Range and cardiorenal complications of T2DM. This video provides an introduction to the case of Tom, which can then be followed on the page below.

Tom, 53-year-old lorry driver

The requirements of his job have contributed to his sedentary lifestyle, which in turn has led to issues with his weight. Despite these factors, Tom doesn’t see a need to change the way he lives his life as he’s felt “fine”. Encouraged by his wife, Tom visits his GP surgery for a regular blood pressure check.

Tom is a patient profile created for the purposes of this case study, drawn from characteristics of real-world patient cases.

Patient presentation

Tom has a BMI of 32 kg/m2 and a waist circumference of 98 cm (39 in).

He is on atorvastatin 20 mg once daily for hyperlipidaemia and lisinopril 2.5 mg once daily for hypertension.

He has visited the practice nurse for a blood pressure check, which showed that his blood pressure is 155/90 mmHg.

The practice nurse recognises that the patient has presented with metabolic syndrome, and suggested an additional HbA1c test.

    It is important the HCP is able to recognise metabolic syndrome as it is a marker of a constellation of risk factors which carry with them a higher risk for the development of both cardiovascular disease and type 2 diabetes.5

    Metabolic syndrome has been defined by the International Diabetes Federation as central obesity plus any two of the following four factors:6

    Raised triglycerides

    Raised triglycerides

    ≥ 150 mg/dL (1.7 mmol/L) or specific treatment for this lipid abnormality

    Reduced HDL cholesterol

    Reduced HDL cholesterol

    < 40 mg/dL (1.03 mmol/L) in males
    < 50 mg/dL (1.29 mmol/L) in females
    Or specific treatment for this lipid abnormality

    man
    Raised blood pressure

    Raised blood pressure

    Systolic BP ≥ 130 or diastolic BP ≥ 85 mm Hg or treatment of previously diagnosed hypertension

    Raised fasting plasma glucose

    Raised fasting plasma glucose

    (FPG) ≥ 100 mg/dL (5.6 mmol/L)

    Or previously diagnosed T2D

    If above 5.6 mmol/L or 100 mg/dL OGTT strongly recommended but is not necessary to define presence of the syndrome

      HbA1c has been established as the practical way of diagnosing diabetes and prediabetes
      - although there are some patient groups for whom this test should not be relied upon.7

      HbA1c not only provides a reliable measure of chronic hyperglycaemia but also correlates well with the risk of long-term diabetes complications.3,8 The HbA1c blood test reflects average blood glucose level over the past 2 to 3 months.8

      HbA1c targets should be individualised taking into account age and comorbidities.9 However, the goal for most adults with diabetes is an HbA1c that is less than 7%.9,10 For adults with T2DM managed either by lifestyle and diet, or by lifestyle and diet combined with a single drug not associated with hypoglycaemia, NICE recommends aiming for an HbA1c level of 6.5%. Although for adults on a drug associated with hypoglycaemia, the HbA1c target should then be 7.0%.9

      Test result shows he has an HbA1c of 6.4% (46 mmol/mol) and is diagnosed as prediabetic.

      He was offered lifestyle advice and a repeat blood test every year to check that he has not progressed to type 2 diabetes.

        If a patient has an HbA1c level of 6.0%-6.4% then they can be considered prediabetic and are at risk of developing type 2 diabetes.11

        A diagnosis of type 2 diabetes should be suspected if an adult presents with persistent hyperglycaemia that may be accompanied by clinical features.

        Persistent hyperglycaemia being defined as:12

        • HbA1c of 48 mmol/mol (6.5%) or more.
        • Fasting plasma glucose level of 7.0 mmol/L or more.
        • Random plasma glucose of 11.1 mmol/L or more in the presence of symptoms or signs of diabetes

        It should be noted that diagnosis of diabetes cannot be based on a single HbA1c/FPG reading if the person is asymptomatic. A second HbA1c/FPG should be taken to confirm the diagnosis, with the same test being used on each occasion.12 If the diagnosis is not confirmed, the patient should be treated as having prediabetes.

        If a person has symptoms of hyperglycaemia the diagnosis is confirmed if one blood test is in the diabetes range.

        Progression to T2DM

        Unfortunately, Tom was diagnosed a year later as having type 2 diabetes, with an HbA1c of 8.3% (67 mmol/mol). He was given metformin and provided with further lifestyle advice. However, his HbA1c remained uncontrolled at follow up.

        The importance of getting HbA1c levels swiftly to the nondiabetic range (HbA1c ~7%) through intense treatment has been shown in UKPDS trials, which demonstrated the impact of uncontrolled blood glucose on future cardiorenal events.3


        A 1% (11 mol/mol) decrease in HbA1c correlates with reduction in the risk of some complications3

        case study graph

         p<0.05 for all analyses
        Data based on prospective observational analysis of UK Prospective Diabetes Study (UKPDS) 35 patients (n = 4585, incidence analysis; n = 3642,
        relative risk analysis). Median follow-up of 10 years. HbA1c, glycated haemoglobin3,13

          Time in Range

          While Time in Range is not in widespread use, the concept that the overall glycaemic burden is important to bear in mind and that this may not be fully reflected in the HbA1c. Although measurement of HbA1c is the established method for assessing glycaemic control and remains the gold standard, it does have certain limitations.14

          Time in range is an emerging concept as a way of looking at the overall glycaemic burden of the patient. This concept is being driven by an increased usage of continuous glucose monitoring in T2DM. It may become a more robust way of assessing patients’ glycaemic burden than HbA1c, and a better guide to treatment optimisation.14

          Time in Range (TIR), the percentage of time that a patient is within the glycaemic range of 70 to 180 mg/dL, represents glucose monitoring beyond HbA1c, capturing variation – the highs, lows, and in-range values that characterise life with diabetes.14

          TIR has been shown to be strongly associated with the risk of microvascular complications.15

          Time in Range goals may vary depending on medication, diet, age, health and risk of hypoglycaemia.14

          In general, people living with diabetes should aim to spend as much time in range as possible, taking care to avoid glycaemic excursions above or below target.14

          Time in Range goals for people living with diabetes14

          Graph image

          T2DM complications

          In addition to his uncontrolled HbA1c, at a later visit, test results show that Tom has moderate renal disease with a creatinine level of 110 μmol/L and eGFR of 55 mL/min/1.73m2.

          The EASD and KDIGO guidelines encourage doctors to test both eGFR and UACR (or urinary ACR) at least once a year in patients with chronic kidney disease and type 2 diabetes.10, 16

          The presence of diabetic nephropathy will influence the treatment provided to the patient. This complication is responsible for the death of around 10% of people with type 2 diabetes.17 In spite of this, only about 70% of people living with type 2 diabetes in England had an ACR test as part of their annual review in 2019-20.18

          T2DM complications

          Treatment Options

          In light of Tom’s reduced renal function, the SGLT2 inhibitor canagliflozin at 100mg once daily is introduced.

          The decision to add on canagliflozin is based on findings from the CREDENCE
          trial which suggests renal protective properties of canagliflozin in patients with type 2 diabetes.19

          Kidney icon

          In the CREDENCE trial, canagliflozin 100mg is shown to reduce renal function decline by 60% vs. placebo.19

          gif graph

          Canagliflozin could delay progression to dialysis by approximately 13 years (95% CI 9.3,17.5)*21

          *Mathematical estimation only based on the rates from CREDENCE (median follow up of 2.6 years)21

          In addition, as shown in the CANVAS and CREDENCE trials, canagliflozin reduces cardiovascular risks in T2DM patients by reducing the risk of major adverse cardiovascular events and hospitalisation for heart failure.19, 22-24

          VIEW THE CREDENCE TRIAL AND CANVAS PROGRAMME STUDY DESIGNS
          icon

          Although the glycaemic efficacy of canagliflozin is reduced in patients who have moderate renal impairment, in a pooled analysis of patients (N = 721) with a baseline of eGFR 45 mL/min/1.73 m2 to < 60 mL/min/1.73 m2, canagliflozin provided clinically meaningful reduction in HbA1c compared to placebo, with -0.47% for canagliflozin 100 mg.22

          Summary

          In this case study we have seen how patients can progress to type 2 diabetes which may lead to the development of renal complications.

          However, for those T2DM patients who do develop renal disease, treatment with canagliflozin may offer potential benefits.

          Dr Image

          Dr. Amrit Lamba explores in more detail some of the clinical considerations that this case presents.

          WATCH T2DM EXPERT TALKS

          Reporting adverse events

          Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard.

          Adverse events should also be reported to Napp Pharmaceuticals Limited on 01223 424444 or drugsafetyuk@napp.co.uk.

          Abbreviations: ARR: Absolute Risk Reduction; BMI:Body mass Index, CI: Confidence Interval; CKD: chronic kidney disease; CANVAS: Canagliflozin Cardiovascular Assessment Study; CREDENCE: Canagliflozin and Kidney Events in Diabetes with Established Nephropathy Clinical Evaluation; CV: cardiovascular; eGFR: estimated Glomerular Filtration Rate; ESKD: end-stage kidney disease; HHF: Hospitalisation for Heart Failure; HCP: Healthcare Professional; HbA1c: Haemoglobin A1c; HR: Hazard Ratio; MACE: major adverse cardiovascular events; MI: myocardial infarction; NNT: Number Needed to Treat; RRR: Relative Risk Reduction; SGLT2: Sodium-Glucose Co-transporter 2; SoC: Standard of care; T2DM: Type 2 Diabetes Mellitus; TIR: time in range; UKPDS: UK Prospective Diabetes Study

          References:

          1. IDF Diabetes Atlas, 2021. https://diabetesatlas.org/ [Last accessed April 2022].
          2. National Diabetes Audit (NDA) 2021-22 quarterly report for England, Clinical Commissioning Groups and GP practices. https://digital.nhs.uk/data-and-information/publications/statistical/national-diabetes-audit [Accessed April 2022].
          3. Stratton IM, et al. BMJ. 2000;321:405-412.
          4. Winocour PH, et al (2020) Diabetes & Primary Care 22: 99–109.
          5. Saklayen MG, Curr Hypertens Rep 2018;20:20
          6. IDF. The IDF consensus worldwide definition of Metabolic Syndrome, 2006.
          7. WHO. Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus, 2011.
          8. Sherwani SI, et al. Biomarker Insights 2016:11 95–104.
          9.  NICE. Type 2 diabetes in adults: management (NG28), 2015, update February 2022. https://www.nice.org.uk/guidance/ng28 [Last accessed April 2022]
          10. Cosentino F, et al; Eur Heart J. 2020;41(2):255–323.
          11. Diabetes UK. Prediabetes. https://www.diabetes.org.uk/preventing-type-2-diabetes/prediabetes [Last accessed April 2022].
          12.  NICE. Clinical Knowledge Summaries. Diabetes – type 2. https://cks.nice.org.uk/topics/diabetes-type-2/diagnosis/diagnosis-in-adults/ [Last accessed April 2022].
          13. The Diabetes Trials Unit. UKPDS overview. https://www.dtu.ox.ac.uk/ukpds/ [Last accessed April 2022].
          14. Diatribe Learn. Making sense of diabetes – Time in Range. https://diatribe.org/time-range [Last accessed April 2022].
          15. Beck R, et al. Diabetes Care 2019;42:400–405.
          16. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int Suppl. 2013;3(1):1–150.
          17. Jikraknatee J, et al. Sci Rep. 2020 Apr 10;10(1):6205. doi: 10.1038/s41598-020-63443-4.
          18. NHS Digital. National Diabetes Audit, 2019-20 Annual Report, 2021.
          19. Perkovic V, et al. N Engl J Med. 2019;380(24):2295-2306.
          20. Jardine MJ, et al. J Am Soc Nephrol. 2020;31(5):1128-1139.
          21. Durkin M, et al. Diabetes Ther. 2021;12(2):499-508.
          22. Invokana Summary of Product Characteristics. https://www.medicines.org.uk/emc/product/8855. [Last accessed April 2022].
          23. Neal B, et al. N Engl J Med. 2017;377(7):644-657.
          24. Giorgino F, et al. Diabetes Obes Metab. 2020;22(9):1481–1495.

          Date of preparation: April 2022

          Job code: UK-INV-2200119