Impact of Anaemia on HbA1c Interpretation Among Normogylcaemic Individuals With Diabetes Mellitus: A Clinical Laboratory Observational Study.

BACKGROUND AND AIM: Over the past decades, glycosylated haemoglobin (HbA1c) has been a gold standard for monitoring diabetes control over a long period, relative to blood glucose level (BGL) which measures short-term results. It is speculated that anaemia and factors that induce haemolysis may cause falsely elevated HbA1c leading to 'false positive' interpretations. This study aimed to investigate how anaemia impacts HbA1c. METHODS: This was a pathology-based observational pilot study using archived data of diabetic subjects monitored with both BGL and HbA1c in regional New South Wales (NSW), Australia. A total of 28,487 cases of blood glucose results were pooled and those with HbA1c and anaemia results were evaluated for correlation with the BGL results. Data collection was limited to de-identified information from the laboratory information system, hence details on the ethnicity and medical history were unavailable. Descriptive frequencies and Pearson correlations were performed. RESULTS: In the pooled data, 53.36% of individuals were females, and 50.54% had BGL ≥5.6 mmol/L. In the pilot dataset, the majority (64.86%) were males, 18.92% with BGL ≤5.6 mmol/L and 67.57% had HbA1c (≥6.5%). In the entire dataset, BGL was moderately and positively correlated with HbA1c (r = 0.6), whereas in the subset of individuals with normo-BGL and anaemia, the correlation was negative (r = -0.2). DISCUSSION: This pilot investigation observed a pertinent issue, which is a negative correlation between glycaemia and HbA1c in patients with anaemia. HbA1c was falsely increased despite normal blood glucose levels in individuals with anaemia. This advances the speculation that anaemia falsely increases HbA1c. Therefore, caution is necessary while interpreting HbA1c results for patients with anaemia, and new methods for interpretation are required.

Inflammation and oxidative stress markers in diabetes and hypertension.

BACKGROUND: Inflammation and oxidative stress are important factors associated with chronic disease such as essential hypertension (HTN) and type 2 diabetes mellitus (T2DM). However, the association of inflammation and oxidative stress in HTN with T2DM as a comorbidity is inconclusive due to the multifactorial nature of these cardiometabolic diseases. METHODOLOGY: The influence of pathophysiological factors include genetics, age of patient, and disease progression change throughout the lifespan and require further investigation. The study population included 256 participants attending a rural health screening program who were tested for markers of inflammation, oxidative stress, and coagulation/fibrinolysis. Demographic and clinical variables included, age, gender, systolic and diastolic blood pressures, blood glucose, hemoglobin A1c, estimated glomerular filtration rate, and cholesterol profile. Data were tested for normality, and nonparametric statistics were applied to analyze the sample with significance set at p<0.05. RESULTS: Of the inflammatory markers, interleukin-1ß (IL-1ß) and IL-10 were significantly different between the control and hypertensive group (p<0.03) and between the HTN+T2DM compared to the HTN group (p<0.05). Significant results for oxidative stress were observed for urinary 8-iso-PGF2α and insulin-like growth factor 1 (IGF-1) between the control and the HTN+T2DM group (p<0.01). Glutathione (GSH) was also significant between the HTN and HTN+T2DM group (p<0.05). Investigation of the progression of HTN also found significant changes in the inflammatory markers IGF-1, monocyte chemoattractant protein 1 (MCP-1), and (MCP-1/IGF-1)*IL-6 (p<0.05). CONCLUSION: This study demonstrated that 8-iso-PGF2α and erythrocyte GSH may be clinically useful for assessing HTN and HTN with T2DM as a comorbidity, while significant changes in the inflammatory profile were also observed with HTN progression.

Hyperglycaemia, oxidative stress and inflammatory markers.

INTRODUCTION: The increasing prevalence of hyperglycaemia implicates a state of oxidative stress and inflammation. Traditional and emerging biomarkers associated with increasing hyperglycaemia were assessed to clarify their role they play in hyperglycaemia. RESULTS: 309 participants attending a rural diabetic screening program were categorised into control and quintile groups based upon glucose levels: 1st quintile - <4.5 mmol/L and 4th, 5th quintile - >6.1 mmol/L. Significant results were obtained for anthropometric data and biochemical markers - glucose, HbA1c and total cholesterol (P < 0.001); oxidative stress: glutathione (P < 0.001), glutathione:glutathione disulfide and 8-hydroxy-2-deoxyguanosine (P < 0.05). Interleukin -1ß and inflammatory marker ratios IL-6/IL-10, IL-1ß/IL-10, MCP-1/IL-10, IGF-1/IL-10 and IL-6/IL-1ß were significant (P < 0.05). CONCLUSION: This study provided further evidence that inflammatory and oxidative stress biomarkers may contribute to diagnostic information associated with preclinical increases in BGL. Further we have provided a unique study in the analysis of ratios of inflammatory biomarkers and correlations with increasing BGL.

Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study.

OBJECTIVE: This study compared acute and late effect of single-bout endurance training (ET) and high-intensity interval training (HIIT) on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. DESIGN: Cohort study with repeated-measures design. METHODS: Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL), IL-1ß, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1), insulin growth factor 1 (IGF-1), and C-reactive protein (CRP). Statistical analysis was with Wilcoxon signed-rank tests. RESULTS: ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (-20%; p = 0.047) and a decrease of MCP-1 (-17.9%; p = 0.03). CONCLUSION: This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis.

New guidelines for diagnosis of gestational diabetes: pathology-based impact assessment.

BACKGROUND: A recent study indicated an average of 19.5% abnormal oral glucose tolerance in antenatal clients per year. AIM: The purpose of this study was to determine the impact on gestational diabetes cases due to new guidelines for diagnosis and classification of hyperglycaemia in pregnancy. MATERIALS AND METHODS: This study reviewed the archived clinical pathology data on oral glucose tolerance tests performed between January 1999 and December 2008 on antenatal clients (N = 615). The cases were reviewed to determine changes if any in percentage of gestational diabetes due to new guidelines. RESULTS: Over the 10 years period, a yearly average of additional 10.8% antenatal cases suggestive of gestational diabetes was observed due to the new recommended thresholds. Further, the average yearly incidence would have increased from 8.8 cases to 16.2 cases, which translates to almost 46% increase in the prospective numbers of gestational diabetes. CONCLUSIONS: This report presents the extent of how the new recommended guidelines for diagnosis and classification of hyperglycaemia in pregnancy could increase the prevalence of gestational diabetes. It also provides pathology-based evidence for the epidemiology of gestational diabetes mellitus and allows for planning the costs that would be attendant to the full implementation of the new guidelines.

Whole blood viscosity assessment issues III: Association with international normalized ratio and thrombocytopenia.

BACKGROUND: Anticoagulant and antiplatelet therapies are being used interchangeably or in combination. While international normalized ratio is assessed to determine anticoagulant's contraindication/need, whole blood viscosity is not assessed to determine the need for antiplatelet. AIMS: The objective of this study is to investigate whether whole blood viscosity value is associated with levels of international normalized ratio and platelet count. MATERIALS AND METHODS: De-identified archived clinical pathology data for the year 2008 were audited. All cases of international normalized ratio, which were concomitantly tested for haematocrit and total proteins, were extracted (n=7,387). Whole blood viscosity levels were extrapolated. Whether differences are associated with normal vs. high international normalized ratio and thrombocytopenia vs. thrombocytosis were evaluated. RESULTS: Multivariate analysis show that whole blood viscosity levels statistically significantly differs between international normalized ratio and platelet counts (p<0.001). Platelet count is statistically significantly lower in low blood viscosity when compared with hyperviscosity and normoviscosity (p<0.001). Conversely, international normalized ratio is statistically significantly higher in low blood viscosity relative to hyperviscosity (p<0.001) and normoviscosity (p<0.002). No difference was observed between hyperviscosity and normoviscosity in platelet count or international normalized ratio. CONCLUSION: The observation corroborates with previous reports to suggest putting into perspective the specificity of whole blood viscosity relative to stasis, against which antiplatelet is employed. It indicates that low whole blood viscosity is synonymous to high international normalized ratio whereby anticoagulant and antiplatelet therapies are contraindicated. International normalized ratio, platelet count and blood viscosity are laboratory indices to consider in constituting antiplatelet monitoring panel.

Whole blood viscosity determination in diabetes management: perspective in practice.

BACKGROUND: Antiplatelet and antioxidant nutritional therapies (ANT) are commonly used in diabetes management. Guidelines recommend identifying deficiencies of antioxidant vitamins and condition of no contraindication for nutritional and antiplatelet respectively. AIM: To determine whether the guidelines recommendations for diabetes patients to be assessed for (1) antioxidant vitamins' deficiencies and/or (2) whole blood viscosity (WBV) as indication of no antiplatelet contraindication. MATERIALS AND METHOD: Laboratory records were audited. 10,342 de-identified glycaemic index (HbA1(c)) requests received in 2008 were sorted into three groups based on level of control. (1) Poor (n = 1962, HbA1(c) ≥ 8.1); (2) Good (n = 5616, HbA1(c) = 6.0 - 8.0) and (3) Excellent (n = 2764, HbA1(c) ≤ 5.9). All 57 cases with haematocrit and total protein results in the poor (n=30) and excellent (n=27) groups were selected for calculation and comparison of WBV levels. RESULTS: None of the two guidelines' recommendations are being followed as no case was requested for any antioxidant vitamin or WBV. Assessments of the latter show that WBV is statistically significantly lower (p < 0.05) in the group with excellent glycaemic control compared to the group with poor glycaemic control. CONCLUSION: Aspirin is one of the therapies in diabetes management. Its effect is modulated by WBV. ANT is alternative to aspirin and influences WBV. For patients that have full blood count and plasma protein results, WBV can be extrapolated at no extra cost to the health system. There is a need to raise awareness for the recommended guidelines for laboratory monitoring to be followed.