Combination therapy as a potential risk factor for the development of type 2 diabetes in patients with schizophrenia: the GOMAP study.

BACKGROUND: Schizophrenia (SCZ) is associated with increased risk of type 2 diabetes (T2D). The potential diabetogenic effect of concomitant application of psychotropic treatment classes in patients with SCZ has not yet been evaluated. The overarching goal of the Genetic Overlap between Metabolic and Psychiatric disease (GOMAP) study is to assess the effect of pharmacological, anthropometric, lifestyle and clinical measurements, helping elucidate the mechanisms underlying the aetiology of T2D. METHODS: The GOMAP case-control study (Genetic Overlap between Metabolic and Psychiatric disease) includes hospitalized patients with SCZ, some of whom have T2D. We enrolled 1653 patients with SCZ; 611 with T2D and 1042 patients without T2D. This is the first study of SCZ and T2D comorbidity at this scale in the Greek population. We retrieved detailed information on first- and second-generation antipsychotics (FGA, SGA), antidepressants and mood stabilizers, applied as monotherapy, 2-drug combination, or as 3- or more drug combination. We assessed the effects of psychotropic medication, body mass index, duration of schizophrenia, number of hospitalizations and physical activity on risk of T2D. Using logistic regression, we calculated crude and adjusted odds ratios (OR) to identify associations between demographic factors and the psychiatric medications. RESULTS: Patients with SCZ on a combination of at least three different classes of psychiatric drugs had a higher risk of T2D [OR 1.81 (95% CI 1.22-2.69); p = 0.003] compared to FGA alone therapy, after adjustment for age, BMI, sex, duration of SCZ and number of hospitalizations. We did not find evidence for an association of SGA use or the combination of drugs belonging to two different classes of psychiatric medications with increased risk of T2D [1.27 (0.84-1.93), p = 0.259 and 0.98 (0.71-1.35), p = 0.885, respectively] compared to FGA use. CONCLUSIONS: We find an increased risk of T2D in patients with SCZ who take a combination of at least three different psychotropic medication classes compared to patients whose medication consists only of one or two classes of drugs.

Biventricular myocardial function in Covid-19 recovered patients assessed by speckle tracking echocardiography: a prospective cohort echocardiography study.

Although severe acute respiratory syndrome coronavirus 2 causes respiratory disease, it may also lead to cardiovascular involvement with unknown long-term consequences. The aim of our study was to evaluate prospectively cardiac involvement in patients after the recovery from Covid-19, using two-dimensional speckle tracking echocardiography. 100 Covid-19 recovered patients with preserved left ventricular ejection fraction, were included, divided based upon clinical manifestation into two groups, those who were treated ambulant and those who were hospitalized. All patients underwent echocardiographic evaluation after their recovery. Although overall LV systolic function expressed by EF was normal, left ventricular global longitudinal strain (LVGLS) was significantly lower in Covid-19 recovered patients (33.28 ± 9.4 days after diagnosis) compared to controls (- 18.47 ± - 2.4 vs. - 21.07 ± - 1.76% respectively, p < 0.0001). Εspecially the lateral wall longitudinal strain (LATLS) and posterior wall longitudinal strain (POSTLS) were significantly reduced in all patients compared to controls (- 17.77 ± - 3.48 vs. - 20.97 ± - 2.86%, p < 0.0001 and - 19.52 ± - 5.3 vs. - 22.23 ± - 2.65%, p = 0.01). right ventricular global longitudinal strain (RVGLS) was significantly diminished only in the hospitalized group of Covid-19 recovered patients, compared to controls (- 18.17 ± - 3.32 vs. - 26.03 ± - 4.55% respectively, p < 0.0001). LVGLS is affected in almost all individuals after Covid-19 infection independently of the infection severity, with LATLS being the most sensitive marker of LV impairment and with POSTLS to follow. RV shows impaired GLS in severely ill patients highlighting RVGLS as a helpful tool of prognosis. Recovered patients from Covid-19 infection have to be monitored for a long time, since the term "long Covid disease" might also include the cardiac function.

Evidence for genetic contribution to the increased risk of type 2 diabetes in schizophrenia.

The epidemiologic link between schizophrenia (SCZ) and type 2 diabetes (T2D) remains poorly understood. Here, we investigate the presence and extent of a shared genetic background between SCZ and T2D using genome-wide approaches. We performed a genome-wide association study (GWAS) and polygenic risk score analysis in a Greek sample collection (GOMAP) comprising three patient groups: SCZ only (n = 924), T2D only (n = 822), comorbid SCZ and T2D (n = 505); samples from two separate Greek cohorts were used as population-based controls (n = 1,125). We used genome-wide summary statistics from two large-scale GWAS of SCZ and T2D from the PGC and DIAGRAM consortia, respectively, to perform genetic overlap analyses, including a regional colocalisation test. We show for the first time that patients with comorbid SCZ and T2D have a higher genetic predisposition to both disorders compared to controls. We identify five genomic regions with evidence of colocalising SCZ and T2D signals, three of which contain known loci for both diseases. We also observe a significant excess of shared association signals between SCZ and T2D at nine out of ten investigated p value thresholds. Finally, we identify 29 genes associated with both T2D and SCZ, several of which have been implicated in biological processes relevant to these disorders. Together our results demonstrate that the observed comorbidity between SCZ and T2D is at least in part due to shared genetic mechanisms.