Depression in Diabetic Patients: What Is the Link With Eating Disorders? Results of a Study in a Representative Sample of Patients With Type 1 Diabetes

Comorbidity between diabetes and depression, and diabetes and eating disorders (ED) conveys significant diagnostic, clinical and therapeutic implications. The present study was conducted on a sample of adult outpatients affected by Type 1 Diabetes (T1DM) to assess lifetime prevalence of ED; current prevalence of depression and Disturbed Eating Behaviors (DEB) and their impact on glycemic control. We hypothesized that patients with depression would have higher rates of lifetime ED and current DEB. We hypothesized a significant and independent association between DEB and the prevalence of depression

Antagonism of convulsions but failure to enhance GABA(A) receptor function by felbamate in mice tolerant to diazepam

The transfer of tolerance between drugs may indicate a common mode of action. The development of cross-tolerance to the anticonvulsant effect of felbamate after long-term treatment of mice with diazepam, a positive modulator of gamma-aminobutyric acid (GABA)-mediated transmission, was therefore studied in order to clarify the mechanism of this action of felbamate. A challenge injection of felbamate, administered 36 h after the last dose of chronic diazepam treatment, antagonized convulsions elicited by administration of isoniazid. In contrast, felbamate had no effect on the isoniazid-induced increase in t-[S-35]butylbicyclophosphorothionate binding to cerebral cortical membranes of diazepam-tolerant mice. These results suggest that the action of felbamate on GABAergic transmission is not required for the anticonvulsant effect of this drug. This conclusion is consistent with studies that have indicated that the antiepileptic activity of felbamate depends on its modulatory activity at excitatory amino acid receptors

The degeneration of the excitatory climbing fibers enhances [3H]MK-801 and [3H]CGP 39653 binding sites in the rat cerebellar cortex.

The effect of a single injection of 3-acetylpyridine (3-AP), which led to a degeneration of the excitatory cerebellar climbing fibers, was studied on the binding of [3H]MK-801, a non-competitive NMDA antagonist, in the rat cerebellar cortex. The same treatment increased also the binding of [3H]CGP 39653, a new NMDA competitive antagonist. Saturation isotherms showed a significant increase of the maximal number of binding sites (Bmax) for [3H]CGP 39653 and [3H]MK-801 (+48 and 36% respectively) with no change in the affinity 4-9 days after the administration of 3-AP. Our data demonstrate that in the cerebellar cortex both NMDA recognition site labelled by [3H]CGP 39653 and its modulatory site labelled by [3H]MK-801 may undergo plastic changes when the glutamatergic receptors and transmission are denervated

Biochemical evaluations of the effects of loreclezole and propofol on the GABA(A) receptor in rat brain

The effects of loreclezole on the function of the gamma-aminobutyric acid type A. (GABA(A)) receptor complex in rat cerebral cortical membrane preparations were compared with those of propofol and diazepam. Loreclezole and propofol modulated [H-3]muscimol binding and t-[S-35]butylbicyclophosphorothionate ([S-35]TBPS) binding to washed and unwashed membranes with potencies and efficacies greater than those of diazepam. Loreclezole and propofol enhanced [H-3]flunitrazepam binding to washed membranes with efficacies lower than those of GABA and muscimol. Both loreclezole and propofol showed biphasic effects on [S-35]TBPS binding to washed membranes: at low concentrations (5 to 10 mu M), both drugs, with different efficacies, enhanced [S-35]TBPS binding whereas, at higher concentrations (30 to 100 mu M), they inhibited this biochemical parameter. In contrast, diazepam enhanced [S-35]TBPS binding to washed membranes at all concentrations tested. The combination of loreclezole with GABA, at a concentration (0.3 mu M) that only slightly increased [S-35]TBPS binding to washed membranes, reversed the increase in binding elicited by loreclezole (5 to 10 mu M) and significantly potentiated the inhibitory effect exerted by higher concentrations (30 to 100 mu M) of this drug. Similar effects were observed with the combination of GABA and propofol. However, GABA had no effect on the enhancement of [S-35]TBPS binding induced by diazepam. The ability of GABA to reverse and potentiate the effects of loreclezole and propofol on [S-35]TBPS binding to washed membranes was shared by pentobarbital (200 mu M) and alphaxalone (3 mu M). These anesthetics showed greater efficacies in combination with propofol than with loreclezole. These results suggest that, unlike diazepam, loreclezole and propofol may activate the receptor-associated Cl- channel in the absence of GABA. Furthermore, the difference in the pharmacological profiles of loreclezole and propofol may result from their different effectiveness in activating the receptor Cl- channel directly

THE JOURNAL OF PHARMACOLOGY Pharmacology of 'y-Aminobutyric AcidA Receptor Complex after the in Vivo Administration of the Anxioselective and Anticonvulsant 3-Carboline Derivative Abecarnil1

ABSTRACT ABBREVIATIONS: GABA, -y-aminobutync acid; CNS, central nervous system; abecamil, isopropyl-6-benzyloxy-4-methoxymethyl-fl-carboline-3-carboxylate; [ S]TBPS, t-[' S]butylbicyclophosphorothionate; ANOVA, analysis of variance

Assessment of eating disorders with the diabetes eating problems survey - revised (DEPS-R) in a representative sample of insulin-treated diabetic patients: A validation study in Italy

Background: The purpose of the study was to evaluate in a sample of insulin-treated diabetic patients, with type 1 or type 2 diabetes, the psychometric characteristics of the Italian version of the DEPS-R scale, a diabetes-specific self-report questionnaire used to analyze disordered eating behaviors. Methods: The study was performed on 211 consecutive insulin-treated diabetic patients attending two specialist centers. Lifetime prevalence of eating disorders (EDs) according to DSM-IV and DSM-5 criteria were assessed by means of the Module H of the Structured Clinical Interview for DSM IV Axis I Disorder and the Module H modified, according to DSM-5 criteria. The following questionnaires were administered: DEPS-R and the Eating Disorder Inventory - 3 (EDI-3). Test/retest reproducibility was assessed on a subgroup of 70 patients. The factorial structure, internal consistency, test-retest reliability and concurrent validity of DEPS-R were assessed. Results: Overall, 21.8% of the sample met criteria for at least one DSM-5 diagnosis of ED. A "clinical risk" of ED was observed in 13.3% of the sample. Females displayed higher scores at DEPS-R, a higher percentage of at least one diagnosis of ED and a higher clinical risk for ED. A high level of reproducibility and homogeneity of the scale were revealed. A significant correlation was detected between DEPS-R and the 3 ED risk scales of EDI-3. Conclusions: The data confirmed the overall reliability and validity of the scale. In view of the significance and implications of EDs in diabetic patients, it should be conducted a more extensive investigation of the phenomenon by means of evaluation instruments of demonstrated validity and reliability

LGR5 deficiency deregulates Wnt signaling and leads to precocious Paneth cell differentiation in the fetal intestine.

The orphan Leucine-rich repeat G protein-coupled receptor 5 (LGR5/GPR49), a target of Wnt signaling, is a marker of adult intestinal stem cells (SC). However, neither its function in the adults, nor during development of the intestine have been addressed yet. In this report, we investigated the role of LGR5 during ileal development by using LGR5 null/LacZ-NeoR knock-in mice. X-gal staining experiments showed that, after villus morphogenesis, Lgr5 expression becomes restricted to dividing cells clustered in the intervillus region and is more pronounced in the distal small intestine. At day E18.5, LGR5 deficiency leads to premature Paneth cell differentiation in the small intestine without detectable effects on differentiation of other cell lineages, nor on epithelial cell proliferation or migration. Quantitative RT-PCR experiments showed that expression from the LGR5 promoter was upregulated in LGR5-null mice, pointing to the existence of an autoregulatory negative feedback loop in intact animals. This deregulation was associated with overexpression of Wnt target genes in the intervillus epithelium. Transcriptional profiling of mutant mice ileums revealed that LGR5 function is associated with expression of SC and SC niche markers. Together, our data identify LGR5 as a negative regulator of the Wnt pathway in the developing intestine.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Long-term benefits of dapagliflozin on renal outcomes of type 2 diabetes under routine care: a comparative effectiveness study on propensity score matched cohorts at low renal risk

Background Despite the overall improvement in care, people with type 2 diabetes (T2D) experience an excess risk of end-stage kidney disease. We evaluated the long-term effectiveness of dapagliflozin on kidney function and albuminuria in patients with T2D. Methods We included patients with T2D who initiated dapagliflozin or comparators from 2015 to 2020. Propensity score matching (PSM) was performed to balance the two groups. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) from baseline to the end of observation. Secondary endpoints included changes in albuminuria and loss of kidney function. Findings We analysed two matched groups of 6197 patients each. The comparator group included DPP-4 inhibitors (40%), GLP-1RA (22.3%), sulphonylureas (16.1%), pioglitazone (8%), metformin (5.8%), or acarbose (4%). Only 6.4% had baseline eGFR <60 ml/min/1.73 m(2) and 15% had UACR >30 mg/g. During a mean follow-up of 2.5 year, eGFR declined significantly less in the dapagliflozin vs comparator group by 1.81 ml/min/1.73 m(2) (95% C.I. from 1.13 to 2.48; p < 0.0001). The mean eGFR slope was significantly less negative in the dapagliflozin group by 0.67 ml/min/1.73 m(2)/year (95% C.I. from 0.47 to 0.88; p < 0.0001). Albuminuria declined significantly in new-users of dapagliflozin within 6 months and remained on average 44.3 mg/g lower (95% C.I. from-66.9 to-21.7; p < 0.0001) than in new-users of comparators. New-users of dapagliflozin had significantly lower rates of new-onset CKD, loss of kidney function, and a composite renal outcome. Results were confirmed for all SGLT2 inhibitors, in patients without baseline CKD, and when GLP-1RA were excluded from comparators. Interpretation Initiating dapagliflozin improved kidney function outcomes and albuminuria in patients with T2D and a low renal risk. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)