# fasting glucose with point-of-care method C: HbA 1 c measurement in laboratory

## care testing and early diagnosis of diabetes and pre-diabetes

### B: fasting glucose with point-of-care method C: HbA 1 c measurement in laboratory

D: HbA 1 c measurement with point-of-care method (p=O. 02, Fisher's Exact test)

60.0%

50.0%

40.0%

30.0%

20.0%

10.0%

.0% A B C D

Health Care Professionals

Diabetes specialist nurses

Doctors

D Primary care practice nurses

A+ C A+ B A + B + C + D Answers to question 8

The majority of the health care professionals follow the guidelines for the diagnosis of diabetes based on a fasting glucose measured in a laboratory and approximately 35% is using HbA1c in combination with fasting glucose for the diagnosis of diabetes.

138

Figure 7 Answers on question 8

At an HbA1c level of 7.0% DCCT I expect a reliability within a margin of: ...

(For clarity reasons only DCCT values are shown, p<0.001 Fisher's Exact test)

50.0%

45.0%

40.0%

35.0%

### c

3o.oo;.

Cl)

GI 25.0%

20.0%

1 5.0%

10.0%

5.0%

.0%

Health Care Professionals

### ■

Diabetes specialist nurses

### □

Doctors

D Primary care practice nurses

<0.1 % 0.1 % 0.2% 0.3% 0.4% 0.5% 0.6% 0.75% >1 .0%

Absolute HbA1 c % DCCT

Figure 7 shows that most of the DSN and PCPN consider an HbA1c value an absolute value and are not aware of the fact that every HbA1c results know some uncertainty based on the analytical performance of the used HbA1c method.

Figure 8 Answers on question 9:

At an HbA1c level of 9.0% DCCT I expect a reliability within a margin of: ..

(For clarity reasons only DCCT values are shown, p<0. 001 Fisher's Exact test)

Figure 8 shows the same results as figure 7.

140

Discussion

Guidelines are necessary to define treatment modalities and treatment goals, as well as to assure quality in diabetes care management. When adhered to properly, they are meant to guarantee that every patient will be treated in more or less the same fashion. In the Netherlands there is an unique system, where the majority of the diabetes patients in prima7a care are seen and controlled by primary care practice nurses for most of the time a)_ These primary care practice nurses are trained to take over special tasks of the general practitioner and one of these tasks is the management of patients with diabetes. In general, when patients are difficult to manage or with other concomitant diseases, they will be referred to special diabetes secondary care centres. All health care professionals are supposed to work with the guidelines for the management of patients with diabetes. However, the results presented in this paper show that nurses are stricter in following protocols than doctors. This could partly be explained by the fact that most of the nurses consider an HbA1c value as an absolute value and are not aware of the fact that every HbA1c result know some uncertainty based on the analytical performance of the HbA1c method used (Figure 7 and 8). As a consequence, nurses tend to consider treatment changes based on very small or even no difference in subsequent HbA1c results.

Figure 4 and 5 shows also that doctors and nurses interpret HbA1c differently when concluding that there is a worsening or improvement of glycemic control. A decrease of at least 5 mmol/mol (0.5%-DCCT) or 1 1 mmol/mol (1 .0%-DCCT) at an HbA1c value of 75 mmol/mol (9.0%-DCCT) after adjustment of therapy, is considered sufficiently by all health care professionals to allow the conclusion that glucose regulation has improved. In contrast, a very small or no increase of HbA1c is considered by most of the diabetes specialist nurses and primary care practice nurses as sufficiently to allow the conclusion that glucose regulation has worsened. These results were in line with the literature (9,1 0l.

In general, guidelines consider a difference of 5 mmol/mol (0.5%-DCCT) as clinically significant. However, a recent study showed that the analytical performance of some HbA1c methods is not accurate enough to sufficiently support treatment decisions in the management of patients with diabetes when differences in serial HbA1c measurements amount to 5 mmol/mol (0.5%-DCCT) or less(5)_ Another study showed that six of eight HbA1c POC instruments do not meet the general accepted performance criteria(6l. Combining this with the outcome of this survey, we can conclude that most of the primary care practice nurses and diabetes specialist nurses may react on HbA1c outcome variations based on the variability of the HbA1c method used instead of the true changes in the degree of glucose control. As a consequence, this could lead to undue treatment changes with accompanying costs and/or inconvenience for the patient. Also several studies have confirmed that, especially for older patients, the benefit of lowering the HbA1c value at every cost (patient inconvenience) is limited and may even lead to a higher mortality rate(3,1 1,12>.

Mean HbA1c of patients with diabetes in primary health care in the Netherlands is amongst the lowest in the world(8l, and studies like the DCCT and the UKPDS showed very clearly that strict controlled patients have a lower risk on developing

1,2

reasonable balance between treating the patient in as well as possible and feasible, and overmanaging of the patient.

To achieve this, we believe that every health care professional should be supplied with the information they need to interpret HbA1c values properly. The reference change value (RCV), which is defined as the critical difference between two consecutive HbA1c measurements representing a significant change in health status, might be a valuable tooI(13,14l_ The analytical CV (CVa) of the used HbA1c method and the within person biological CV (CVw) are necessary to calculate the RCV (RCV (%)

= -{i x 1.96 x

### ✓

[(CV3 )2 + (CVw)2] ). The analytical performance of different HbA1c methods is ranging from poor (most of the POC instruments and some immunoassays) to state of the art (newer version cation-exchange HPLCt·5·15·16l. It is not realistic to assume that every health care professional knows the analytical performance of every HbA1c method, not even the method used by his or her main providing laboratory.

Directors of laboratories or other decision makers are responsible for the choice of the HbA1c method. This choice is based on many factors like analytical performance (which is hopefully the most important factor), sample throughput (commercial labs), costs per test, support of and contact with the manufacturer etc. The RCV makes clear what the impact is of bad performing methods and is hopefully a stimulant for directors of laboratories to choose for a method with acceptable analytical performance which allows changing therapy based on small changes in HbA1c values.

More exchange of knowledge is necessary between clinical chemistry where the results are produced and diabetes medicine where the results are interpreted. The clinical chemist can help clinical decision making by providing healthcare professionals with the necessary information (RCV) to properly interpret HbA1c results.

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References

1 . The Diabetes Control and Complications Trial Research Group, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus, N Engl J Med, 1 993;329:977-986.

2. UK Prospective Diabetes Study (UKPDS) Group, Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33), Lancet, 1 998;352:837-853.

3. Currie CJ, Peters JR, Tynan A, Evans M, Heine RJ, Bracco OL, Zagar T, Poole CD. Survival as a function of HbA1 c in people with type 2 diabetes: a retrospective cohort study. Lancet 201 0;375:481-89.

4. Lenters-Westra E, Slingerland RJ. Six of Eight hemoglobin A1 c point-of-care instruments do not meet the general accepted analytical performance criteria. Clin Chem 201 0;56:44-52

5. Lenters-Westra E, Weykamp CW, Schindhelm RK, Siebelder C, Bila HJ, Slingerland RJ. One in five laboratories using various Hemoglobin A 1 c methods do not meet the criteria for optimal diabetes care management Diab Tech Ther 201 1 ;1 3:429-433.

6. IDF Guidelines.http://www.idf.org/webdata/docs/lDF%20GGT2D.pdf (assessed March 201 1 ) 7. Nathan OM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B: Medical

management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32:1 93-203.

8. Logtenberg SJJ, Kleefstra N, Ubink-Veltmaat LJ, Houweling ST, Bila HJG. Glucoseregulatie Type 2 diabetes mellitus bij ketenzorg anno 2005 (ZODIAC-?). Ned. Tijdschrift voor Diabetologie 2007;5:1 5-1 8.

9. Skeie S, Thue G, Sandberg S. Use and interpretation of HbA1 c testing in general practice.

Implications for quality of care. Scand J Clin Lab Invest 2000;60:349-356.

1 0. Skeie S, Thue G, Sandberg S. Interpretation of Hemoglobin A1 c (HbA1 c) values among diabetic patients: implications for quality specifications for HbA1c, Clin Chem 2001 ;47:1212-1217.

1 1 . Landman GW, Hateren KJJ, KLeefstra N , Greenier KH, Gans ROB, Bila HJG. The relationship between glycaemic control and mortality in patients with type 2 diabtes in general practice (ZODIAC-1 1 ). Br J Gen Pract 201 0;60:1 72-1 75.

12. Graffy J. Tailoring treatment to risk in type 2 diabetes. Br J Gen Pract 201 0;60:1 58-160.

1 3. Omar F, van der Watt GF, Pillay TS: Reference change values: how useful are they? J Clin Pathol 2008;61 :426-427.

14. Rices C, Cava F, Garcia-Lario JV, Hernandez A, Iglesias N, Jimenez CV, Minchinela J, Perich C, Simon M, Domenech MV, Alvarez V: The reference change value: a proposal to interpret

1 6. Weykamp CW, Lenters-Westra E, Van der Vuurst H, Slingerland RJ, Siebelder C, Visser-Dekker W. Evaluation of the Menarini/ARKRAY ADAMS A1 c HA-81 80V analyser for HbA1c. Clin Chem Lab Med 201 1 ;49:647-651 .

### Summary, conclusions, recommendations and

Outline

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