Abstract
Coexisting diabetes mellitus and sickle cell disease (SCD) markedly increases the risk of organ damage, particularly nephropathy. Adequate detection of type 2 diabetes mellitus (T2DM) and optimal glycaemic control are essential to prevent rapid deterioration of renal function. In the UK, T2DM is typically managed in primary care, and predominantly relies on glycosylated haemoglobin (HbA1c). HbA1c reflects the average blood sugar levels over the preceding 2-3 months and is a reliable predictor of diabetes-related end-organ damage.
However, in individuals with SCD, HbA1c is unreliable due to the presence of abnormal haemoglobin and the shortened lifespan of red blood cells. Similarly, in patients who have recently received blood transfusions, HbA1c does not accurately reflect glycaemic status.
METHODS
We conducted a retrospective audit of T2DM screening and management in SCD patients registered with King's College Hospital (KCH) and residing in the Boroughs of Lambeth, Southwark, or Lewisham. The Trust Governance Board approved the audit (00000643). We reviewed hospital records of all patients aged 35 years or older. Primary care data were accessed through the London Care Record; a health information exchange portal linked to the patients' hospital records. We collected data on demographics, genotype, diagnosis of T2DM, QDiabetes Risk Assessment (QDRA; an algorithm developed by the UK National Health Service (NHS); http://qdiabetes.org), fasting glucose, HbA1c, fructosamine, oral glucose tolerance test (OGTT) and self-monitoring devices. Reported HbA1c was compared with calculated HbA1c when a fructosamine result was also available using the paired-sample t-test. Fructosamine was converted to HbA1c using the formula (((0.017*fructosamine)+1.61)-2.152)/0.09148. This formula does not correct for interference with bilirubin levels.
RESULTS
Records of 225 patients were available for review. The average age was 44 (ranging 35-69). Eighteen patients (8%) had a known diagnosis of T2DM. Genotypes included HbSS 115 (51%), HbSC 85 (38%), HbS/beta(+) 16 (7%) and HbS/beta(0) 8 (4%).
Risk assessment and screening in SCD patients NOT known to have a diagnosis of T2DM
207/225 patients (92%) did not have T2DM.
QDRA was completed for 145/207 (70%) patients.
57/145 patients (39%) had a high-risk QDRA score, 88 (61%) had a low-risk score.
47/57 of high-risk patients (82%) underwent T2DM screening.
Of the remaining 150 patients, 95 (63%) also had a T2DM screening test.
Altogether, a total of 142/207 (69%) individuals were screened for T2DM.
Screening methods used
Fasting glucose levels in 4 patients (3%).
OGTT in 1 patient (1%).
Fructosamine in 34 patients (24%). (25/34 arranged by the sickle cell specialist centre rather than by primary care).
HbA1c in 128 patients (90%).
Ninety-five patients (67%) were screened using HbA1c as the sole test. The cumulative number of patients not adequately assessed (either no risk assessment performed and/or HbA1c as the only test) was 173/207 (84%).
Monitoring of glycaemic control in SCD patients WITH a known diagnosis of T2DM.
Fourteen out of 18 patients (78%) used a glucose meter (n=13) and/or CGM device (n=5), and/or fructosamine levels.
In 3/18 (17%) HbA1c was used as the single method.
When both a HbA1c and fructosamine result were available, we looked at the difference between reported and calculated HbA1c. In 29 non-diabetic SCD patients, the mean reported HbA1c was 28.4 mmol/mol (SD 12.4), versus a calculated HbA1c of 48.8 mmol/mol (SD 9.8), respectively (P<0.001). Similarly, in 10 diabetic SCD patients the mean reported HbA1c was 37.9 mmol/mol (SD 16.4), versus a calculated HbA1c of 64.1 mmol/mol (SD 14.1), respectively (P<0.001).
DISCUSSION
Effectively, only 16% of the patients in our cohort underwent an adequate assessment. The findings highlight the inadequacy of HbA1c as a tool for both the screening and monitoring of T2DM in SCD. When applying the average discrepancy of 22 mmol/mol between reported and calculated HbA1c values to patients for whom only an HbA1c result was available, an additional 37 patients (39%) would have had an adjusted HbA1c of 50 mmol/mol or above - consistent with a potential diagnosis of T2DM. Similarly, 2/3 patients (67%) with T2DM would have had a HbA1c of 53 mmol/mol or above, thus not meeting the NHS target for T2DM glycaemic control. Our data highlight the unmet need for appropriate risk assessment, screening and monitoring for T2DM in SCD in primary healthcare in the UK.
