Effect of dehydration on blood tests
In this third article in our ‘Test tips’ series, Dr Muhammad Masood Ashraf and Dr Rustam Rea examine the effects of dehydration on all essential diabetes blood tests, and provide guidance on key practical points to consider.
Dehydration is common in patients presenting to the acute admissions ward. The most common reasons include poor oral intake and fluid loss from:
• Gastrointestinal tract (e.g. diarrhoea, vomiting).
• Skin (e.g. fever, burns).
• Urine (e.g. glucosuria, diuretic therapy, diabetes insipidus, diabetic ketoacidosis).
A reduction of the central circulating blood volume due to hypovolaemia accompanying dehydration results in a fall in cardiac filling pressure and stroke volume and, if uncompensated, a fall in cardiac output. The body can compensate by moving water from the extravascular to the intravascular space.1,2 As a result of these fluid shifts, changes in electrolytes and water concentrations in various body compartments occur which are reflected in many blood tests results. This is classically seen in patients with diabetic ketoacidosis and Hyperglycaemic Hyperosmolar State (previously HONK).
The clinical and biochemical features of dehydration3 are summarised in Box 1.
Box 1. Summary of the clinical and biochemical features of dehydration3
Effect of dehydration on haemoglobin, haematocrit and HbA1c
Both haemoglobin and haematocrit increase in a dehydrated person.2,4 Hiroshi Nose1 and colleagues induced dehydration in 10 subjects by exercise and checked haemoglobin (Hb), haematocrit (Hct), Na, K+, Cl, and plasma osmolality at 0 minutes, 30 minutes and 60 minutes after exercise. Figure 1 shows the change in Hct, Hb, and plasma solids before and after dehydration. Immediately after exercise, these increased from 42.7±0.5% to 44.7±0.5%, 14.8±0.2g/dl to 15.8±0.2g/dl, and 8.4±0.1g/dl to 9.1±0.1g/dl, respectively. The significant differences observed before and after dehydration were maintained for the next 60 minutes.
Figure 1. Haematocrit (Hct), haemoglobin (Hb) concentration, and plasma (Pl) solids are shown as means ± SE of 10 subjects before (C) and at 0, 30, and 60 minutes after dehydration. Significant differences were observed for all variables between control and dehydrated conditions (0, 30, and 60 minutes). There were significant differences between 0 minutes and the other 2 dehydrated conditions (30 and 60 minutes)
HbA1c is the measure of glycaemic status of an individual over the last three months.5 It is formed by a non-enzymatic reaction which occurs between glucose and the N-end of the beta chain.5 There is very little literature available on data search to suggest that dehydration directly affects HbA1c. However, a rise in urea level as a result of dehydration can alter the HbA1c test results depending on the assay.6
One study showed that in patients with uraemia, HbA1c measured by ion exchange chromatography was significantly elevated, but this was not correlated with the degree of glucose intolerance.7 This was due to the excessive amount of cyanate derived from the urea, which causes carbamylation at the N-terminal valine residue. This carbamylated haemoglobin (carbHb) results in an increase in the HbA1 (a + b) and, hence, the increased levels of HbA1.6,8 However, newer ion-exchange HPLC assay methods show improved separation of the HbA1c fraction from other haemoglobin fractions and therefore no interference from carbHb.9
Effect of dehydration on CBG measurements
Hypotension as a result of dehydration results in decrease in perfusion and increase in glucose utilisation in the local tissue leading to false low results of capillary blood glucose (CBG) tests. One study assessed the validity of the CBG measurements in the hypotensive, critically-ill patients. Capillary glucose values were significantly lower than those obtained from testing venous blood on the reagent strips and also lower than laboratory glucose measurements. Capillary glucose values in the hypotensive group were 33% lower than venous laboratory glucose values, and were significantly lower than the values obtained in the normotensive group.10
Effect of dehydration on blood glucose
One study has looked at the effect of dehydration in frogs and demonstrated that dehydration can increase blood glucose levels.11 The rise in glucose was found to be out of proportion to changes in metabolite concentrations that could be due to passive concentration of the plasma (haemoconcentration) as a result of dehydration. Glucose was significantly elevated even in 12.2% of dehydrated frogs and rose progressively to a final level 23.6 times higher than controls in 50% of dehydrated frogs.
Another study showed an increase in hepatic glucose production, with increased plasma glucose levels during hyperosmolality which can be caused by dehydration.12 The very high levels of venous glucose seen in patients with Hyperglycaemic Hyperosmolar State often resolve rapidly with rehydration alone without the need for insulin. This would suggest a significant effect of dehydration on venous glucose concentration.
Effect of dehydration on renal function tests
Dehydration has multiple effects on the kidney. The loss of body water leads to an increase in serum osmolality and activation of vasopressin which results in urinary concentration.13 This can be seen clearly in the above given Vignette.
Nose1 and colleagues also demonstrated sustained effects on plasma electrolyte concentration before and after dehydration (Figure 2).
Figure 2. Changes in electrolyte concentrations and osmolality (Posmol) in plasma after dehydration. Significant differences were observed for all variables between control (C) and dehydrated conditions (0, 30, and 60 minutes)
However, there is an exception in the case of patients with cranial diabetes insipidus (CDI).
Dehydrated patients usually present with an elevated serum urea level, owing in part to increased renal reabsorption of urea mediated by antidiuretic hormone (ADH). Serum urea values fall in patients with ADH deficiency (CDI) and this fact can be used to distinguish patients dehydrated because of CDI from those with usual hypertonic dehydration and intact ADH secretion. In one study, the mean serum urea level was 2.9mmol/L in the CDI group and 15.4mmol/L in the patients without CDI, while the mean serum sodium level was 155mmol/L in both groups.13
Effect of dehydration on lipid profile
The effect of dehydration on lipid profile has been investigated in fasting subjects.14 Subjects were fasted, initially with no fluid replacement and then with salt and water supplementation. Subjects who had fasted with no fluids had a higher total serum cholesterol, HDL cholesterol, LDL cholesterol, apolipoprotein A-1, and apolipoprotein B, compared to subjects who had fasted with prior fluid and salt replacement.
Effect of dehydration on liver function tests
The above given Vignette demonstrates a significant difference in serum total proteins and albumin levels in a dehydrated patient, before and after hydration with intravenous fluids. However, bilirubin and liver enzymes levels remained unchanged, indicating that changes in protein levels were essentially due to hydration status rather than liver abnormality per se.
Clinicians should take the hydration status of the patient into account before interpreting the laboratory results. Before routine blood tests, patients should avoid unnecessary physical activity, avoid hot dry environments, ensure adequate intake of water, and avoid diuretic substances such as caffeine.
1. Institute of Medicine (US) Committee on Military Nutrition Research. Fluid Replacement and Heat Stress. Washington (DC): National Academies Press (US), 1994. doi: 10.17226/9071.
2. Nose H, et al. Distribution of water losses among fluid compartments of tissues under thermal dehydration in the rat. Jpn J Physiol 1983;33:1019–29.
3. El-Sharkawy AM, et al. The pathophysiology of fluid and electrolyte balance in the older adult surgical patient. Clin Nutr 2014;33:6–13.
4. Holsworth RE, et al. Effect of hydration on whole blood viscosity in firefighters. Altern Ther Health Med 2013;19:44–9.
5. Bunn HF, et al. The biosynthesis of human hemoglobin A1c. Slow glycosylation of hemoglobin in vivo. J Clin Invest 1976;57:1652–9.
6. Fluckiger R, et al. Hemoglobin carbamylation in uremia. N Engl J Med 1981;304:823–7.
7. de Boer MJ, et al. Glycosylated haemoglobin in renal failure. Diabetologia 1980;18:437–40.
8. Standing SJ, Taylor RP. Glycated haemoglobin: an assessment of high capacity liquid chromatographic and immunoassay methods. Ann Clin Biochem 1992;29(Pt 5):494–505.
9. Little RR, et al. Measurement of HbA1c in patients with chronic renal failure. Clin Chim Acta 2013;418:73–6.
10. Atkin SH, et al. Fingerstick glucose determination in shock. Ann Intern Med 1991;114(12):1020–4.
11. Churchill TA, Storey KB. Metabolic effects of dehydration on an aquatic frog, Rana pipiens. J Exp Biol 1995;198:147–54.
12. Keller U, et al. Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health. Eur J Clin Nutr 2003;57(Suppl 2):S69–S74.
13. Comtois R, et al. Low serum urea level in dehydrated patients with central diabetes insipidus. CMAJ 1988;139:965–9.
14. Campbell NR, et al. Dehydration during fasting increases serum lipids and lipoproteins. Clin Invest Med 1994;17:570–6.