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An unexpected danger--hypoglycaemia
- Zekria Ibrahimi (6 June 2009)
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Reactive hypoglycemia in non-diabetic patients with severe mental illness.
- Ruud van Winkel, Marc De Hert, University Psychiatric Centre Catholic University Leuven, Leuvensesteenweg 517, 3070 Kortenberg, Belgium. (9 June 2009)
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Zekria Ibrahimi, psychiatric patient Coombs Library UB1 3EU
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The Maudsley guidelines have no reference to hypoglycaemia as a side effect of anti-psychotics(1). What is unfortunately expected is the reverse- hyperglycaemia. The three case studies on hypoglycaemia in schizophrenic patients indicate a reaction that is dose dependent, and varies according to which drug is deployed (2). The mystery nowadays is: are atypical antipsychotics directly producing insulin resistance, through some putative receptor X (3)? The alternative is that they are indirectly establishing it through weight gain in the metabolic syndrome. The implication of the three case studies is that antipsychotics can disrupt insulin response in both directions- so either hyperglycaemia or hypoglycaemia may result. There is proposed some sort of metabolic tug of war. How were these patients different? What else was wrong with them , apart from the glucose levels? Without fruitful idiosyncracies such as these three cases, we cannot pull the solution out of a general medical problem. Historically, insulin coma therapy actually was the artificial, cruel and deliberate induction of hypoglycaemia in a patient (4). Also, even before anti- psychotic drugs were devised in the 1950's, there was a putative association between schizophrenia and diabetes (5). Chlorpromazine, the initial archetypal anti- psychotic, became linked subsequently to diabetes (6). This article by Yutaro Suzuki et al is, then, part of the extended tension between schizophrenia and sugar. REFERENCES: (1)The Maudsley Prescribing Guidelines. 9th Edition. 2007. (2)Drug Point: Hypoglycaemia induced by second generation antipsychotic agents in schizophrenic non- diabetic patients. BMJ 2008;337:a1792. (3)Which comes first: atypical antipsychotic treatment or cardiometabolic risk? S.M. Stahl, L.Mignon, J.M.Meyer. Acta Psychiatr Scand 2009:119:pg. 175. (4) Mad In America. Bad Science, Bad Medicine, and the Enduring Mistreatment of the Mentally Ill. Robert Whitaker. Perseus. 2002. Pg.85. (5)Diabetes mellitus and schizophrenia: historical perspective. D. Kohen. s64. B J Psych Vol. 184 Supplement 47. (6)Cardiovascular Risk Associated with Schizophrenia and its treatment. Ed. J. Camm. Galliard. 2003. Pg. 33. (Adverse metabolic effects of atypical antipsychotics by Ali Dana and Michael Marber) Competing interests: None declared |
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Ruud van Winkel, Psychiatrist, Assistant Professor Maastricht University Medical Centre; PO box 616, 6200 MD Maastricht, The Netherlands., Marc De Hert, University Psychiatric Centre Catholic University Leuven, Leuvensesteenweg 517, 3070 Kortenberg, Belgium.
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We have read the letter by Suzuki and colleagues (1) with great interest. It describes another potential metabolic complication in patients with schizophrenia who are treated with a second-generation antipsychotic, in addition to an increased risk for hyperglycemia associated with the use of some second-generation antipsychotics (e.g. see (2)). The letter concerns three cases of suspected reactive hypoglycemia in whom the diagnosis was made based on symptomatology suggestive of hypoglycemia and a demonstration of a glucose level below 3.9 mmol/l after two hours in a 75 gram oral glucose tolerance test (OGTT). The letter raises two important questions: 1) is there evidence for an increased prevalence of reactive hypoglycemia in patients with schizophrenia?, and 2) do second-generation antipsychotics induce reactive hypoglycemia? As of 2003, we have tested all patients treated with antipsychotic medication in follow-up at the University Psychiatric Centre of the University of Louvain (Belgium) using a standard protocol including an OGTT (3, 4). As such, our data may help to examine the above questions. In a sample of 707 non-diabetic patients with severe mental illness (SMI) screened for metabolic disturbances, 2223 OGTTs were conducted over the course of a 4-year period (November 2003 – July 2007). Of these patients, 503 were diagnosed with schizophrenia, 92 with schizoaffective disorder and 112 with bipolar disorder (see (5) for an extensive description of recruitment and screening procedures). The number of patients having a glucose level below 3.9 mmol/l in any of the 2223 OGTTs was 19.2%; 10.6% had a glucose level between 3.9 and 3.3 mmol/l, 5.9% had a glucose level between 3.3 and 2.8 mmol/l and 2.7% had severe hypoglycemia, defined as a glucose level below 2.8 mmol/l at 120 minutes. Using multilevel regression to investigate predictors of hypoglycemia at 120 minutes in the OGTT using a three-stage cut-off (‘0’: >3.9 mmol/l, ‘1’: <3.9 and >3.3 mmol/l, ‘2’: <3.3 and >2.8 mmol/l, ‘3’: <2.8 mmol/l), we found that neither insulin resistance (‘HOMA-IR’), type of antipsychotic medication, diagnosis, age, race or sex was associated with an increased risk for hypoglycemia. The risk for hypoglycemia was negatively associated with fasting glucose levels (â= -0.01, SE 0.002, p=0.001), fasting insulin (â= -0.01, SE 0.003, p<0.001), BMI (â= -0.02, SE 0.005, p<0.001) and a worse overall metabolic profile as indicated by presence of the metabolic syndrome according to the adapted ATP III criteria (â= -0.28, SE 0.06, p<0.001) in multivariate regression models covarying for age, sex, race, type of antipsychotic medication and diagnosis. It is important to note that none of the patients presenting with a glucose level below 3.9 mmol/l had previously received a diagnosis of reactive hypoglycemia or had issued complaints possibly relating to hypoglycemia prior to the OGTT. In interpreting these data therefore, prevalence rates of hypoglycemia in asymptomatic healthy individuals need to be considered. For example, Fariss and colleagues found that 7.4% of military draftees had a 2-hour post-load glycemia below 2.7 mmol/l in an OGTT (6). Occasionally, values as low as 1.9 mmol/l are found in asymptomatic healthy individuals during the course of an OGTT (7). Although we did not recruit a healthy control group, these data in healthy individuals suggest that the prevalence of hypoglycemia in our sample of 707 patients with SMI was not unusually high. In addition, we were unable to confirm that (certain) second-generation antipsychotics induce reactive hypoglycemia, as was provocatively suggested by Suzuki and colleagues. This is in line with the clinical description of two of the three cases, in whom mild hypoglycemia persisted after antipsychotic medication was changed. Thus, the data leave open the possibility that second-generation antipsychotics aggravate pre-existing (mild) reactive hypoglycemia, but the examination of more than 2000 OGTTs indicates that there is little evidence to suggest these agents actually induce reactive hypoglycemia in SMI patients. The authors declare they do not have competing interests. 1. Suzuki Y, Watanabe J, Fukui N, Ozdemir V, Someya T. Hypoglycaemia induced by second generation antipsychotic agents in schizophrenic non- diabetic patients. BMJ 2009;338:a1792. 2. van Winkel R, De Hert M, Wampers M, Van Eyck D, Hanssens L, Scheen A, et al. Major changes in glucose metabolism, including new-onset diabetes, within 3 months after initiation of or switch to atypical antipsychotic medication in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2008;69(3):472-9. 3. De Hert MA, van Winkel R, Van Eyck D, Hanssens L, Wampers M, Scheen A, et al. Prevalence of the metabolic syndrome in patients with schizophrenia treated with antipsychotic medication. Schizophr Res 2006;83(1):87-93. 4. van Winkel R, De Hert M, Van Eyck D, Hanssens L, Wampers M, Scheen A, et al. Screening for diabetes and other metabolic abnormalities in patients with schizophrenia and schizoaffective disorder: evaluation of incidence and screening methods. J Clin Psychiatry 2006;67(10):1493-500. 5. van Winkel R, van Os J, Celic I, Van Eyck D, Wampers M, Scheen A, et al. Psychiatric diagnosis as an independent risk factor for metabolic disturbances: results from a comprehensive, naturalistic screening program. J Clin Psychiatry 2008;69(8):1319-27. 6. Fariss BL. Prevalence of post-glucose-load glycosuria and hypoglycemia in a group of healthy young men. Diabetes 1974;23(3):189-91. 7. Brun JF, Fedou C, Mercier J. Postprandial reactive hypoglycemia. Diabetes Metab 2000;26(5):337-51. Competing interests: None declared |
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