Loss of hypoglycemia awareness in an adolescent with type 1 diabetes mellitus during treatment with fluoxetine hydrochloride

doi:10.1067/mpd.2000.103851

The Journal of Pediatrics

Volume 136, Issue 3, March 2000, Pages 394-396

https://doi.org/10.1067/mpd.2000.103851 Get rights and content

Abstract

A 17-year-old boy with type 1 diabetes mellitus developed new loss of hypoglycemia awareness while being treated with fluoxetine hydrochloride for depression. Hypoglycemia unawareness resolved after this medication was discontinued. (J Pediatr 2000;136:394-6)

Section snippets

CASE REPORT

Our patient, a 17-year-old boy, was diagnosed with diabetes mellitus at the age of 15 years, when he presented with ketoacidosis. He had no evidence of acanthosis nigricans. Islet cell antibodies, ICA512 antibodies, glutamic acid decarboxylase antibodies, and C peptide were not measured. Although he was mildly obese, his clinical presentation was consistent with type 1 diabetes mellitus, and he was treated with an intensive subcutaneous insulin program (preprandial Lis-pro and evening

DISCUSSION

Glucose fuels the central nervous system. However, the brain is unable to synthesize glucose and is dependent on uptake of glucose from the periphery. Hypoglycemia results in a counterregulatory response involving glucagon, epinephrine, growth hormone, cortisol, and hepatic autoregulation.⁴ Classic autonomic warning symptoms (including diaphoresis, hunger, anxiety, and palpitations) typically occur at a blood glucose level of ~3.3 mmol/L (60 mg/dL). Symptoms of neuroglycopenia (confusion,

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Effects of the selective serotonin reuptake inhibitor fluoxetine on glucose metabolism: A systematic review
2022, Asian Journal of Psychiatry
Citation Excerpt :
But LDL decreased significantly in Beyazyüz et al. (2013) (−9.5 mg/dL ± 19 (−9.5 mg/dL ± 19.58, P < 0.001). All three case reports (Biagetti and Corcoy, 2013; Deeg and Lipkin, 1996; Sawka et al., 2000) mentioned hypoglycemic events after taking fluoxetine. The use of fluoxetine is related to hypoglycemic episodes, unconsciousness and increased insulin sensitivity in diabetic patients.
The metabolic effects of antidepressants should be considered when prescribing antidepressants due to the increasing risk of diabetes, obesity and cardiovascular disease. This study aims to explore the effects of fluoxetine on glucose and lipid metabolism in human body. Methods: Studies of the effects of fluoxetine on glucose and lipid metabolism were collected from the PubMed, MEDLINE and Embase databases without limiting the research design. The retrieval spanned between inception and January 2021. The main outcome measures were fasting blood glucose, glycosylated hemoglobin (mainly HbA1c) and body weight. Results: A total of 24 studies were retrieved, including 20 randomized controlled trials (RCTs), 1 prospective study and 3 case reports. The meta-analysis showed that FBG and HbA_1c levels were moderately decreased(MD-0.85[−1.75, −0.13], P = 0.02 and MD-0.55[−1.23, 0.13], P = 0.11 respectively) and body weight was significantly decreased (MD-3.01[−5.58, −0.44], P < 0.00001) with fluoxetine treatment compared with placebo. Both plasma triglyceride (TG) and total cholesterol (TC) levels decreased significantly (P < 0.00001). Conclusion: Fluoxetine had a positive effect on improving blood glucose control in patients with disorders of glucose metabolism and was good for weight management in obese people despite significant heterogeneity between studies.
Human Beta Cells Produce and Release Serotonin to Inhibit Glucagon Secretion from Alpha Cells
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While the hypoglycemic effects of SSRIs have been proposed to be beneficial for diabetic patients (Daubresse et al., 1996), SSRIs may also render diabetic patients susceptible to life-threatening hypoglycemia. Indeed, patients on long-term SSRI treatment have poor counter-regulatory responses (Biagetti and Corcoy, 2013; Deeg and Lipkin, 1996; Derijks et al., 2008; Sawka et al., 2000, 2001; Takhar and Williamson, 1999). In our hands, SSRIs increased paracrine serotonin levels within the islet and inhibited glucagon secretion from alpha cells.
In the pancreatic islet, serotonin is an autocrine signal increasing beta cell mass during metabolic challenges such as those associated with pregnancy or high-fat diet. It is still unclear whether serotonin is relevant for regular islet physiology and hormone secretion. Here, we show that human beta cells produce and secrete serotonin when stimulated with increases in glucose concentration. Serotonin secretion from beta cells decreases cyclic AMP (cAMP) levels in neighboring alpha cells via 5-HT_1F receptors and inhibits glucagon secretion. Without serotonergic input, alpha cells lose their ability to regulate glucagon secretion in response to changes in glucose concentration, suggesting that diminished serotonergic control of alpha cells can cause glucose blindness and the uncontrolled glucagon secretion associated with diabetes. Supporting this model, pharmacological activation of 5-HT_1F receptors reduces glucagon secretion and has hypoglycemic effects in diabetic mice. Thus, modulation of serotonin signaling in the islet represents a drug intervention opportunity.
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Depression is prevalent as a co-morbid condition in diabetes. The efficacy of depression treatment with either pharmacological agents or psychotherapy has been demonstrated in the few available controlled trials. Depression has been associated with poor glycemic control and with accelerated rates of coronary heart disease in diabetic patients. Reported depression treatment trials demonstrate benefits of depression remission on glycemic control as well as mood and the potential for improvement in the course and outcome of diabetes. Because adverse effects of pharmacological agents on glycemic control have been observed, optimal therapies that improve both depression and measures of diabetes are still being sought. This review critically examines the efficacy of depression treatment in diabetes patients, the effects of depression treatment on the medical condition, and methodological issues important in the performance of treatment trials in the patient population.
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Clinical and Laboratory ObservationsLoss of hypoglycemia awareness in an adolescent with type 1 diabetes mellitus during treatment with fluoxetine hydrochloride☆

Abstract

Section snippets

CASE REPORT

DISCUSSION

Clin Ther

Serotonin selective reuptake inhibitors in child and adolescent psychopharmacology: review of published experience

J Clin Psychiatry

Treatment of depression in patients with diabetes mellitus

J Clin Psychiatry

Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction

Am J Physiol

Hypoglycemia unawareness in IDDM

Diabetes Care

A study of fluoxetine in obese elderly patients with type 2 diabetes

Diabet Med

Clinical and Laboratory Observations
Loss of hypoglycemia awareness in an adolescent with type 1 diabetes mellitus during treatment with fluoxetine hydrochloride☆