Glucometabolic Hormones and Cardiovascular Risk Markers in Antipsychotic-Treated Patients

Abstract

Objective: Treatment with antipsychotic drugs is widely associated with metabolic side effects such as weight gain and disturbed glucose metabolism, but the pathophysiologic mechanisms are unclear.Method: Fifty nondiabetic (fasting plasma glucose ≤ 7.0 mmol/L), antipsychotic-treated male patients (ICD-10 diagnosis code F20, F21, F22, F25, F28, or F60; mean ± SD age = 33.0 ± 6.7 years; body mass index [BMI; kg/ m 2 ] = 26.0 ± 4.7; waist circumference = 95.9 ± 13.3 cm; glycated hemoglobin A 1c [HbA 1c ] = 5.7% ± 0.3%) and 93 age-and waist circumference-matched healthy male controls (age = 33 ± 7.3 years; BMI = 26.1 ± 3.9; waist circumference = 94.6 ± 11.9 cm; HbA 1c = 5.7% ± 0.3%) participated in this cross-sectional study. Blood was sampled in the fasting state and 90 minutes after ingestion of a standardized liquid meal (2,268 kJ). The primary outcomes were glucometabolic hormones and cardiovascular risk markers. Data were collected between March 2008 and February 2010.Results: Compared to healthy controls, patients were characterized by elevated fasting levels of proinsulin, C-peptide, and glucose-dependent insulinotropic polypeptide (GIP) (P < .05) and higher postprandial levels of insulin, proinsulin, C-peptide, and GIP (P ≤ .02). Also, patients exhibited elevated plasma levels of C-reactive protein and signs of dyslipidemia. Fasting plasma levels of insulin, glucagon, glucagon-like peptide-1 (GLP-1), ghrelin, leptin, adiponectin, tumor necrosis factor-α, plasminogen activator inhibitor-1, and interleukin-6 and postprandial levels of glucagon, GLP-1, ghrelin, leptin, and adiponectin did not differ between groups. Conclusions:Presenting with an insulin resistant-like pattern, including beta cell hypersecretion and elevated GIP levels, nondiabetic antipsychotic-treated patients display emerging signs of dysmetabolism and a compromised cardiovascular risk profile. The appetite-regulating hormones GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new clinical insight into the pathophysiology associated with metabolic side effects of antipsychotic treatment and put emphasis on the importance of implementing metabolic screening into psychiatric practice.Trial Registration: ClinicalTrials.gov identifier NCT00627757 Clin Psychiatry 2014;75(9):e899-e905 J

Postprandial prolactin suppression appears absent in antipsychotic-treated male patients

“…Controlling for the variables, which we previously reported significantly different between patients and controls (tobacco smoking, daily physical activity, as well as fasting values of proinsulin, C-peptide, and glucosedependent insulinotropic polypeptide (GIP), total cholesterol, low-density lipoprotein cholesterol, triglycerides, and CRP, and postprandial values of insulin, proinsulin, Cpeptide, and GIP (Ebdrup et al, 2014)), did not alter the findings.…”

“…Details of inclusion and exclusion criteria and participants were previously reported (Ebdrup et al, 2014). In short, patients had a diagnosis in the schizophrenia spectrum [ICD-10 diagnosis: F20, F21, F22, F25, F28, F60.1] and all were Caucasian outpatients treated with at least one antipsychotic.…”

Effect of GLP‐1 receptor agonist treatment on body weight in obese antipsychotic‐treated patients with schizophrenia: a randomized, placebo‐controlled trial

“…In contrast to a GLP‐1RA study in non‐diabetic obese patients, we found unexpected significant increases in HbA1c, fasting plasma glucose and lipids after 3 months; however, parallel increases in these parameters were also observed in the placebo group. This could indicate that these metabolic parameters in antipsychotic‐treated patients may not be as responsive to weight loss as would be expected in the background population . In contrast, a study using exenatide twice‐daily and once‐weekly in patients with type 2 diabetes found a significant lowering of HbA1c, regardless of weight loss …”

Metformin attenuates olanzapine-induced hepatic, but not peripheral insulin resistance

“…In this regard, our own work from preclinical rodent models consistently supports pronounced, direct effects on insulin sensitivity (peripheral and hepatic) following acute dosing of specific AP agents (e.g., risperidone, olanzapine (Ola) or clozapine) (Chintoh et al 2008(Chintoh et al , 2009. From a clinical perspective, acute or 'direct' effects are supported by reports of diabetic ketoacidosis occurring shortly after initiation of AP drugs in absence of notable weight changes (Guenette et al 2013), as well as studies that suggest a risk of glucose dysregulation independently of weight gain (Newcomer et al 2002, Henderson et al 2005, Ebdrup et al 2014. These observations support the notion that acute mechanisms can lead to glucose dysregulation in the absence of weight gain, but that over time, these can contribute to notable changes in adiposity.…”