Diabetic ketoacidosis and diabetes associated with antipsychotic exposure among a previously diabetes-naive population with schizophrenia: a nationwide nested case–control study

Polcwiartek, Christoffer; Kragholm, Kristian; Rohde, Christopher; Hashemi, Nasseh; Vang, Torkel; Nielsen, Jimmi

doi:10.1007/s00125-017-4320-5

Cited by 17 publications

(9 citation statements)

References 43 publications

(65 reference statements)

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“…Antipsychotics have partial 5HT 2c properties; full agonists have been shown to reduce insulin secretion in isolated islets in animal studies (48). Finally in vitro effects have suggested clozapine has a direct effect to inhibit glucose-dependent insulin release by β-cell membrane hyperpolarisation (50).…”

Section: Insulin Secretionmentioning

confidence: 99%

Mechanisms in endocrinology: Antipsychotic medication and type 2 diabetes and impaired glucose regulation

Whicher

Price

Holt

2018

European Journal of Endocrinology

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It remains unclear whether these antipsychotic medications exacerbate an underlying predisposition to the development of T2DM or have a direct effect. Potential risks need to be weighed up and balanced between improved and lasting mental health benefits and any detrimental physical health side effects. Achieving parity of esteem between mental and physical health is a worldwide priority if we wish to improve life expectancy and quality of life in people with severe mental illness.

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Section: Insulin Secretionmentioning

confidence: 99%

Mechanisms in endocrinology: Antipsychotic medication and type 2 diabetes and impaired glucose regulation

Whicher

Price

Holt

2018

European Journal of Endocrinology

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“…This is in line with the evidence of a recent large-scale systematic review and meta-analysis [25] that found a prevalence of only 2.9% of T2D in antipsychotic-naïve patients and 11.3% in patients with severe mental illness medicated with SGAs, with the highest prevalence associated with clozapine and olanzapine. A recent nationwide Danish study also reported a significant relationship between exposure to SGAs and diabetic ketoacidosis, caused by insulin deficiency [40]. In another Danish cohort, olanzapine and aripiprazole were shown to increase the rate of T2D in patients with schizophrenia by almost two-fold, whereas clozapine increased the rate four-fold [41].…”

Section: Introductionmentioning

confidence: 99%

Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain

Grajales

Ferreira

Valverde

2019

Cells

109

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Second-generation antipsychotics (SGAs) are the cornerstone of treatment for schizophrenia because of their high clinical efficacy. However, SGA treatment is associated with severe metabolic alterations and body weight gain, which can increase the risk of type 2 diabetes and cardiovascular disease, and greatly accelerate mortality. Several underlying mechanisms have been proposed for antipsychotic-induced weight gain (AIWG), but some studies suggest that metabolic changes in insulin-sensitive tissues can be triggered before the onset of AIWG. In this review, we give an outlook on current research about the metabolic disturbances provoked by SGAs, with a particular focus on whole-body glucose homeostasis disturbances induced independently of AIWG, lipid dysregulation or adipose tissue disturbances. Specifically, we discuss the mechanistic insights gleamed from cellular and preclinical animal studies that have reported on the impact of SGAs on insulin signaling, endogenous glucose production, glucose uptake and insulin secretion in the liver, skeletal muscle and the endocrine pancreas. Finally, we discuss some of the genetic and epigenetic changes that might explain the different susceptibilities of SGA-treated patients to the metabolic side-effects of antipsychotics.

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“…On the other hand, the metabolic effects of psychotropic medications, especially antipsychotics and mood stabilizers, have been of concern in deteriorating the metabolic profile of pediatric patients. In addition, treatments with antipsychotics and antidepressants have also been linked to an increased risk of diabetic ketoacidosis and hypoglycemia . In addition, the appetite change and gastrointestinal adverse effects induced by certain antidepressants and ADHD medication may be challenging for maintaining stable glycemic control.…”

Section: Discussionmentioning

confidence: 99%

Psychotropic Medication Use in Children and Adolescents With Type 1 Diabetes

Liu,

Lagerberg,

Ludvigsson

et al. 2023

JAMA Netw Open

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ImportanceChildren and adolescents with type 1 diabetes (T1D) face elevated risks of psychiatric disorders. Despite their nonnegligible adverse effects, psychotropic medications are a common cost-effective approach to alleviating psychiatric symptoms, but evidence regarding their dispensation to children and adolescents with T1D remains lacking.ObjectiveTo examine the trends and patterns of psychotropic medication dispensation among children and adolescents with T1D in Sweden between 2006 and 2019.Design, Setting, and ParticipantsThis cohort study used data from multiple Swedish registers. The main study cohort included children and adolescents residing in Sweden from 2006 to 2019 and was followed up until the earliest of December 31, 2019, 18th birthday, emigration, or death. Data analyses were conducted from November 1, 2022, to April 30, 2023.ExposuresType 1 diabetes.Main Outcomes and MeasuresThe primary outcomes were trends and patterns of psychotropic medication dispensation (including antipsychotics, antidepressants, anxiolytics, hypnotics, mood stabilizers, and medications for attention-deficit/hyperactivity disorder [ADHD]), psychotropic medication initiation, and history of neurodevelopmental and psychiatric diagnosis. Cumulative incidence curves and Cox proportional hazard models were used to estimate the aggregated incidence and hazard ratios of medication initiation after diabetes onset.ResultsOf 3 723 745 children and adolescents (1 896 199 boys [50.9%]), 13 200 (0.4%; 7242 boys [54.9%]) had T1D (median [IQR] age at diagnosis, 11.1 [7.6-14.7] years). Between 2006 and 2019, psychotropic medication dispensation increased from 0.85% (95% CI, 0.65%-1.10%) to 3.84% (3.11%-4.69%) among children and from 2.72% (95% CI, 2.15%-3.39%) to 13.54% (95% CI, 12.88%-14.23%) among adolescents with T1D, consistently higher than their peers without T1D. The most commonly dispensed medications included hypnotics, ADHD medications, anxiolytics, and selective serotonin reuptake inhibitors, and all exhibited increasing trends. For those with T1D, psychiatric care was the primary prescription source, and up to 50.1% of treatments lasted more than 12 months. In addition, children and adolescents with T1D showed higher cumulative incidence and hazard ratios of medication initiation after diabetes onset than their same-age and same-sex counterparts.Conclusions and RelevanceThis cohort study found an increasing trend in psychotropic medication dispensation among children and adolescents with T1D from 2006 to 2019, persistently higher than those without T1D. These findings call for further in-depth investigations into the benefits and risks of psychotropic medications within this population and highlight the importance of integrating pediatric diabetes care and mental health care for early detection of psychological needs and careful monitoring of medication use.

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Diabetic ketoacidosis and diabetes associated with antipsychotic exposure among a previously diabetes-naive population with schizophrenia: a nationwide nested case–control study

Abstract: Antipsychotic exposure was associated with DKA and type 2 diabetes in a previously diabetes-naive schizophrenia population. Antipsychotic-associated DKA is relevant not only for psychiatrists but also for other physicians who may manage and admit such patients.

Cited by 17 publications

References 43 publications

Mechanisms in endocrinology: Antipsychotic medication and type 2 diabetes and impaired glucose regulation

Mechanisms in endocrinology: Antipsychotic medication and type 2 diabetes and impaired glucose regulation

Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain

Psychotropic Medication Use in Children and Adolescents With Type 1 Diabetes

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