Does Trintellix the Medication Cause False High A1c Readings?

Indian J Endocrinol Metab. 2012 Jul-Aug; 16(4): 528–531.

Drugs affecting HbA1c levels

Ranjit Unnikrishnan

Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India

Ranjit Mohan Anjana

Madras Diabetes Research Foundation and Dr. Mohan'south Diabetes Specialities Centre, Gopalapuram, Chennai, India

Viswanathan Mohan

Madras Diabetes Research Foundation and Dr. Mohan'southward Diabetes Specialities Middle, Gopalapuram, Chennai, Bharat

Abstract

Glycated hemoglobin (HbA1c) is an of import indicator of glycemic control in diabetes mellitus, based on which important diagnostic and therapeutic decisions are routinely made. Withal, there are several situations in which the level of HbA1c may not faithfully reflect the glycemic control in a given patient. Of import among these is the use of certain not-diabetic medications, which can affect the HbA1c levels in different ways. This review focuses on the non-diabetic medications which can inappropriately heighten or lower the HbA1c levels, and the postulated mechanisms for the aforementioned.

Keywords: Dapsone, diabetes, glycated hemoglobin

INTRODUCTION

Diabetes mellitus has assumed epidemic proportions worldwide, causing much morbidity and mortality on account of its various complications. The development of chronic vascular complications of diabetes such as retinopathy, nephropathy and cardiovascular disease is intimately linked to the level of glycemic control attained by the individual with diabetes. Therefore, it is essential to have an alphabetize of the long-term glycemic control in diabetes patients, which in plow can be used to guide therapy and predict the likelihood of complications.

Glycated hemoglobin (HbA1c) was first described by Rahbar et al. in 1969.[ane] Subsequent studies showed that the level of HbA1c correlated well with the glycemic control over a catamenia of 2 to 3 months, leading to the gradual incorporation of the test into clinical practise in the 1980s.[two] With the publication of the Diabetes Command and Complications Trial[3] and the United kingdom of great britain and northern ireland Prospective Diabetes Report,[4] both of which correlated the HbA1c levels to the evolution of diabetes complications, HbA1c estimation has go established as a cornerstone of diabetes direction.

Hemoglobin (Hb) is a tetramer formed of ii alpha and two beta globin bondage. On exposure to high levels of claret glucose, hemoglobin gets non-enzymatically glycated at different sites in the molecule. HbA1c is formed when glucose gets added on to the North-terminal valine rest of the beta chain of Hb.[5] The levels of HbA1c in the claret reflect the glucose levels to which the erythrocyte has been exposed during its lifespan (approximately 117 days in men and 106 days in women). Therefore, the HbA1c is an index of the level of glycemic control over the preceding 2 to 3 months. Of this period, the immediately preceding 30 days contribute 50% to HbA1c.[5]

A number of methods are in use for measuring HbA1c. The most widely used assay utilizes high-functioning liquid chromatography (HPLC). Other methods include boronate affinity analysis and immunoassays. Efforts are underway to standardize the assay worldwide.[6]

The primary use of HbA1c is in the monitoring of patients with diabetes. HbA1c targets of less than 6.5 to 7% have been proposed by various organizations to ascertain expert control of diabetes.[7,8] The efficacy of anti-diabetic medications is also assessed based on their HbA1c lowering capacity. Many algorithms for the management of diabetes utilize HbA1c as the basis for major therapeutic decisions. Recently, HbA1c has also been recommended every bit a tool for the diagnosis of diabetes.[9]

Fallacies in the Utilise of HbA1c

Although HbA1c is, in general, a robust marker of glycemia, there are certain weather condition in which the examination can be unreliable. Use of the newer assays like HPLC can eliminate some, but not all of these errors. Some of the important factors that tin bear on the HbA1c levels are listed in Tabular array one. The remainder of this review will focus on (non-diabetic) drugs which may falsely increment or decrease the HbA1c level.

Table one

Conditions causing inappropriately high or low Hba1c[10]

Drugs and HbA1c

Drugs can theoretically interfere with HbA1c levels in several means [Table 2]. Nevertheless, only a few instances of drug-induced variability in HbA1c accept actually been reported in the literature.

Tabular array 2

Drugs causing inappropriately low or high HbA1c

Drugs causing hemolysis

Any drug which causes hemolysis can potentially lower the HbA1c by reducing erythrocyte lifespan, thereby increasing the proportion of younger cells in the claret. Dapsone, ribavirin and antiretroviral drugs have been reported to reduce the HbA1c in this manner.

The earliest report of dapsone-induced reduction in HbA1c was from the UK in 1979.[eleven] The patient in question had been taking dapsone for dermatitis herpetiformis. Over a menses of five years, his HbA1c declined to iii.7% in spite of uncontrolled claret glucose levels. Further investigation revealed a raised reticulocyte count, indicating hemolysis. Later, in 2002, there was a written report each from French republic[12] and the The states[13] concerning the same phenomenon. The patients in question had been put on dapsone for polychondritis and necrobiosis lipoidica diabeticorum, respectively, and reduction in the dose of dapsone was followed by a render of HbA1c levels to the appropriate range in the latter case. There was no bear witness of pregnant hemolysis in either case, although subclinical hemolysis could not be ruled out. In 2003, Polgreen et al.[14] reported two HIV positive individuals with diabetes who had been put on dapsone for prophylaxis of Pneumocystis carinii infection. Both patients had excellent HbA1c values in spite of loftier self-reported and lab blood glucose measurements. Concomitant utilize of dapsone with sulfapyridine has also been reported to lower the HbA1c in patients with type 1 diabetes.[15] In this issue we have reported two cases of dapsone-induced reduction in HbA1c from India.[sixteen] None of the to a higher place 8 patients had anemia.

Dapsone can too promote the oxidation of hemoglobin to methemoglobin, which may interfere with the HPLC analysis used to mensurate HbA1c. Dapsone has also been postulated to reduce erythrocyte survival contained of its hemolytic outcome.[13]

The potential HbA1c lowering consequence of dapsone assumes special significance in Republic of india in view of the widespread employ of this amanuensis in the treatment of Hansen'southward disease and many other conditions.

Other agents which have been reported to lower the HbA1c levels through hemolysis include ribavirin, antiretroviral agents and sulfonamides. In 2008, Robertson[17] reported the case of a 55-yr-old male patient put on ribavirin for chronic hepatitis C infection, who subsequently presented with an HbA1c level of iv.four%, in spite of persistently loftier blood glucose values. Stoppage of ribavirin was followed past an increase of HbA1c to 6.five%. In a study of 112 HIV-infected individuals, Diop et al.[18] found that the HbA1c underestimated mean fasting glycemia by 12.3% as compared to 1238 non HIV-infected individuals. Treatment with nucleoside counterpart antiretroviral agents was found to be associated with macrocytosis and a low serum haptoglobin level, suggesting the presence of subclinical hemolysis in these patients. In the series quoted to a higher place, Polgreen et al.[fourteen] also reported on an HIV positive patient who presented with inappropriately depression HbA1c levels post-obit administration of trimethoprim-sulfamethoxazole.

In most of the above cases, the caste of hemolysis was not sufficient to produce anemia or jaundice. Other markers of hemolysis like a raised level of lactate dehydrogenase, low serum haptoglobin and increased reticulocyte count, combined with a loftier index of clinical suspicion, were essential in making the diagnosis.

Agents interfering with glycation

High doses of antioxidant agents such equally Vitamin C and E have been reported to lower the HbA1c by reducing the charge per unit of glycation of hemoglobin, simply the caste to which this occurs with pharmacological doses is uncertain. Camargo et al.[xx] did non observe any bear on on the HbA1c when pharmacological doses of vitamin C or E were administered in patients with diabetes for iv months. Chronic apply of aspirin has been reported to falsely decrease the HbA1c by the same mechanism.[10]

Agents altering erythropoiesis

Patients with anemia due to deficiency of iron and vitamin B₁₂ have high HbA1c levels. This tin can be reversed with administration of the scarce factor. In some cases, administration of atomic number 26 and vitamin B₁₂ can pb to falsely lowered HbA1c due to the preponderance of young erythrocytes in the circulation.[20] Treatment with erythropoietin has the aforementioned effect.[22]

Agents altering hemoglobin

Hydroxyurea is an antimetabolite which is used for the treatment of myeloproliferative disorders and sickle cell disease. The drug promotes a shift in the hemoglobin blueprint from HbA to HbF, with a concomitant apparent decrease in HbA1c levels.[19]

Agents interfering with the HbA1c analysis

Chronic utilize of aspirin in big doses tin lead to acetylation of hemoglobin, leading to falsely elevated HbA1c levels due to interference with some of the assays used. Camargo et al.[20] reported an increment of 0.17% in the HbA1c of 28 non-diabetic subjects administered 200 mg of aspirin per mean solar day for 4 months. A subsequent study by the aforementioned author,[23] nevertheless, failed to bear witness any interference of aspirin in the HbA1c (measured by ion-commutation HPLC) in type ii diabetes patients. In clinical practice, the effect of aspirin on HbA1c is likely to be pregnant only when large doses are administered over a long period of fourth dimension.

Chronic opiate use has been reported to increase HbA1c levels,[21] just the verbal mechanism remains unknown.

CONCLUSION

HbA1c is at present universally accepted equally an index of long-term glycemic control and major therapeutic decisions are undertaken based on it. There is increasing interest in using HbA1c for the diagnosis of diabetes likewise. While the availability of newer assays has removed many of the technical problems associated with the estimation of HbA1c, several fallacies remain. There are a number of drugs, some of them quite ordinarily used, which can cause inappropriately high or depression HbA1c levels for the caste of glycemia. It is essential that clinicians be enlightened of these interactions, and exercise caution in interpreting the HbA1c levels of such patients, then that potentially serious errors tin can be avoided.

Footnotes

Source of Support: Nil

Conflict of Interest: None declared.

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401751/

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