Impaired glucose tolerance in first-episode drug-naïve patients with schizophrenia: relationships with clinical phenotypes and cognitive deficits

BackgroundSchizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia.MethodA total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids. They were also compared using a 75 g oral glucose tolerance test and the homeostasis model assessment of insulin resistance (HOMA-IR). Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).ResultsOf the patients, 24.5% had IGT compared with none of the controls, and they also had significantly higher levels of fasting blood glucose and 2-h glucose after an oral glucose load, and were more insulin resistant. Compared with those patients with normal glucose tolerance, the IGT patients were older, had a later age of onset, higher waist or hip circumference and body mass index, higher levels of low-density lipoprotein and triglycerides and higher insulin resistance. Furthermore, IGT patients had higher PANSS total and negative symptom subscale scores, but no greater cognitive impairment except on the emotional intelligence index of the MCCB.ConclusionsIGT occurs with greater frequency in FEDN schizophrenia, and shows association with demographic and anthropometric parameters, as well as with clinical symptoms but minimally with cognitive impairment during the early course of the disorder.

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PM505. Impaired glucose tolerance, symptoms and cognitive deficits in first-episode drug-naïve patients with schizophrenia

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyw041.505 ◽

2016 ◽

Vol 19 (Suppl_1) ◽

pp. 83-84

Keyword(s):

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Cognitive Deficits ◽

First Episode ◽

Drug Naïve

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QOL-43. ENDOCRINE AND METABOLIC CHANGES IN CHILDREN TREATED FOR MEDULLOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa222.700 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii439-iii439

Author(s):

Alexey Kalinin ◽

Natalia Strebkova ◽

Olga Zheludkova

Keyword(s):

Insulin Resistance ◽

Body Composition ◽

Glucose Tolerance ◽

Oral Glucose Tolerance Test ◽

Impaired Glucose Tolerance ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Hormone Deficiency ◽

Oral Glucose ◽

Oral Glucose Tolerance

Abstract We examined 63 patients (40 males/23 females) after complex treatment of medulloblastoma. Patients had a median age (range) of 11.3 (5.5 ÷ 17.9) years. The median time after the end of treatment was 3.7 (1.5 ÷ 11.6) years. Endocrine disorders were detected with the following frequency: growth hormone deficiency - 98.41% (62 of 63 patients), thyroid hormone deficiency – 69.8% (44/63), adrenal hormone deficiency - 17.4% (11/63). Three cases (4.7%) of premature sexual development were also detected. Lipids levels, beta-cell function and insulin resistance (IR) during 2-h oral glucose tolerance test were evaluated. A mono frequent bioelectrical impedanciometer was used to measure body composition. Overweight (SDS BMI> 1) was observed only in 16 patients (3 girls and 13 boys), obesity (SDS BMI> 2) in 1 boy. Dyslipidemia was found in 34 patients (54%). All patients underwent oral glucose tolerance test. Insulin resistance (ISI Matsuda <2.5 and/or HOMA-IR> 3.2) was detected in 7 patients (11/1%), impaired glucose tolerance (120 min glucose ≥7.8 mmol / l) was observed in 2 patients with IR and in 2 patients without IR. At the same time, IR and impaired glucose tolerance were encountered in only 5 children with overweight and no one with obesity. All patients with impaired glucose tolerance had normal values of fasting glucose (4.3 ÷ 5.04 mmol / l) and HbA1c (4.8 ÷ 5.8%). A bioelectrical impedanciometer was used to measure body composition in 49 cases, the percentage of adipose tissue was increased in 14 patients (28%) with normal BMI.

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Effects of Micronutrient Supplementation on Glucose and Hepatic Lipid Metabolism in a Rat Model of Diet Induced Obesity

Cells ◽

10.3390/cells10071751 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1751

Author(s):

Saroj Khatiwada ◽

Virginie Lecomte ◽

Michael F. Fenech ◽

Margaret J. Morris ◽

Christopher A. Maloney

Keyword(s):

Insulin Resistance ◽

Lipid Metabolism ◽

Glucose Tolerance ◽

Antioxidant Capacity ◽

Fasting Glucose ◽

Oral Glucose ◽

Model Assessment ◽

Micronutrient Supplementation ◽

Sprague Dawley ◽

Triglyceride Accumulation

Obesity increases the risk of metabolic disorders, partly through increased oxidative stress. Here, we examined the effects of a dietary micronutrient supplement (consisting of folate, vitamin B6, choline, betaine, and zinc) with antioxidant and methyl donor activities. Male Sprague Dawley rats (3 weeks old, 17/group) were weaned onto control (C) or high-fat diet (HFD) or same diets with added micronutrient supplement (CS; HS). At 14.5 weeks of age, body composition was measured by magnetic resonance imaging. At 21 weeks of age, respiratory quotient and energy expenditure was measured using Comprehensive Lab Animal Monitoring System. At 22 weeks of age, an oral glucose tolerance test (OGTT) was performed, and using fasting glucose and insulin values, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated as a surrogate measure of insulin resistance. At 30.5 weeks of age, blood and liver tissues were harvested. Liver antioxidant capacity, lipids and expression of genes involved in lipid metabolism (Cd36, Fabp1, Acaca, Fasn, Cpt1a, Srebf1) were measured. HFD increased adiposity (p < 0.001) and body weight (p < 0.001), both of which did not occur in the HS group. The animals fed HFD developed impaired fasting glucose, impaired glucose tolerance, and fasting hyperinsulinemia compared to control fed animals. Interestingly, HS animals demonstrated an improvement in fasting glucose and fasting insulin. Based on insulin release during OGTT and HOMA-IR, the supplement appeared to reduce the insulin resistance developed by HFD feeding. Supplementation increased hepatic glutathione content (p < 0.05) and reduced hepatic triglyceride accumulation (p < 0.001) regardless of diet; this was accompanied by altered gene expression (particularly of CPT-1). Our findings show that dietary micronutrient supplementation can reduce weight gain and adiposity, improve glucose metabolism, and improve hepatic antioxidant capacity and lipid metabolism in response to HFD intake.

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Insulin resistance in an animal model of polycystic ovary disease is aggravated by vitamin D deficiency: Vascular consequences

Diabetes and Vascular Disease Research ◽

10.1177/1479164118758580 ◽

2018 ◽

Vol 15 (4) ◽

pp. 294-301 ◽

Cited By ~ 7

Author(s):

Leila Hadjadj ◽

Szabolcs Várbíró ◽

Eszter Mária Horváth ◽

Anna Monori-Kiss ◽

Éva Pál ◽

...

Keyword(s):

Insulin Resistance ◽

Vitamin D ◽

Glucose Tolerance ◽

Vitamin D Deficiency ◽

Vascular Tissue ◽

Female Rats ◽

Oral Glucose ◽

Model Assessment ◽

Coronary Resistance ◽

Vitamin D Receptors

Hyperandrogenic state in females is accompanied with metabolic syndrome, insulin resistance and vascular pathologies. A total of 67%–85% of hyperandrogenic women suffer also from vitamin D deficiency. We aimed to check a potential interplay between hyperandrogenism and vitamin D deficiency in producing insulin resistance and effects on coronary resistance arteries. Adolescent female rats were divided into four groups, 11–12 animals in each. Transdermal testosterone-treated and vehicle-treated animals were kept either on vitamin D-deficient or on vitamin D-supplemented diet for 8 weeks. Plasma sexual steroid, insulin, leptin and vitamin D plasma levels were measured, and oral glucose tolerance test was performed. In coronary arterioles, insulin receptor and vitamin D receptor expressions were tested by immunohistochemistry, and insulin-induced relaxation was measured in vitro on isolated coronary resistance artery segments. Testosterone impaired glucose tolerance, and it diminished insulin relaxation but did not affect the expression of insulin and vitamin D receptors in vascular tissue. Vitamin D deficiency elevated postprandial insulin levels and homeostatic model assessment insulin resistance. It also diminished insulin-induced coronary arteriole relaxation, while it raised the expression of vitamin D and insulin receptors in the endothelial and medial layers. Our conclusion is that both hyperandrogenism and vitamin D deficiency reduce sensitivity of coronary vascular tissue to insulin, but they do it with different mechanisms.

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Correlation between Blood Activin Levels and Clinical Parameters of Type 2 Diabetes

Experimental Diabetes Research ◽

10.1155/2012/410579 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Hui Wu ◽

Michael Wu ◽

Yi Chen ◽

Carolyn A. Allan ◽

David J. Phillips ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Glucose Tolerance ◽

Fasting Glucose ◽

Serum Levels ◽

Activin A ◽

Oral Glucose ◽

Clinical Parameters ◽

Model Assessment

Aims. Activins A and B, and their binding protein, follistatin, regulate glucose metabolism and inflammation. Consequently, their role in type 2 diabetes (T2D) was examined.Methods. Blood was taken from fasted participants (34 males; 58 females; 50–75 years) with diabetes or during an oral glucose tolerance test (OGTT). Clinical parameters were assessed, and blood assayed for activins, follistatin, and C-reactive protein.Results. Serum levels of activin A (93.3 ± 27.0 pg/mL, mean ± SD), B (81.8 ± 30.8 pg/mL), or follistatin (6.52 ± 3.15 ng/mL) were not different (P>0.05) between subjects with normal OGTT (n=39), impaired glucose tolerance and/or fasting glucose (n=17), or T2D (n=36). However, activin A and/or activin B were positively correlated with parameters of insulin resistance and T2D, including fasting glucose (P<0.001), fasting insulin (P=0.02), glycated hemoglobin (P=0.003), and homeostasis model assessment of insulin resistance (HOMA-IR;P<0.001). Follistatin was positively correlated with HOMA-IR alone (P=0.01).Conclusions. These data indicate that serum measurements of activin A, B, or follistatin cannot discriminate risk for T2D in individual patients, but the activins display a positive relationship with clinical parameters of the disease.

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The “Lipid Accumulation Product” Is Associated with 2-Hour Postload Glucose Outcomes in Overweight/Obese Subjects with Nondiabetic Fasting Glucose

International Journal of Endocrinology ◽

10.1155/2015/836941 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Alexis Elias Malavazos ◽

Emanuele Cereda ◽

Federica Ermetici ◽

Riccardo Caccialanza ◽

Silvia Briganti ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Lipid Accumulation ◽

Fasting Glucose ◽

Tolerance Test ◽

Continuous Variable ◽

Oral Glucose ◽

Model Assessment ◽

Lipid Accumulation Product ◽

Adult Age

“Lipid accumulation product” (LAP) is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT) abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR) in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23%) adult (age: 18–70 years) overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m2) having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT) and type-2 diabetes mellitus (T2-DM). According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM) and composite (IGT + T2-DM) abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR (P=0.006andP=0.007, resp.). LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose.

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Pancreatic Iron and Glucidic Metabolism in Thalassemia Major

Blood ◽

10.1182/blood-2019-121876 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3551-3551

Author(s):

Alessia Pepe ◽

Laura Pistoia ◽

Saveria Campisi ◽

Roberto Sarli ◽

Piera Giovangrossi ◽

...

Keyword(s):

Diabetes Mellitus ◽

Glucose Tolerance ◽

Iron Overload ◽

Impaired Glucose Tolerance ◽

Area Under The Curve ◽

Pancreatic Head ◽

Thalassemia Major ◽

Oral Glucose ◽

Model Assessment ◽

Glucose Dysregulation

Background. A preliminary study involving 59 patients demonstrated that pancreatic iron assessed by magnetic resonance imaging (MRI) was the strongest overall predictor of glucose dysregulation in thalassemia major (TM) patients. Aim. In the present multicenter study we explored systematically the link between pancreatic iron and glucidic metabolism in a large cohort of TM patients. Methods. We considered 705 TM patients (372 F, mean age 37.00±9.95 years) enrolled in the E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) project. T2* measurements were performed over pancreatic head, body and tail and global value was the mean. The pattern of disturbances of glucose metabolism was assessed by means of the oral glucose tolerance test (OGTT). Results. According to OGTT results, 546 patients (77.4%) had normal glucose tolerance (NGT), 14 (2.0%) had isolated impaired fasting glucose (IFG), 29 (4.1%) had impaired glucose tolerance (IGT), and 116 (16.5%) had diabetes mellitus (DM). None of the 85 patients (12.1%) without pancreatic iron overload (global pancreas T2*≥26 ms) had IGT or DM (Figure 1). The 84.6% of patients with NGT had pancreatic iron overload. The global pancreatic T2* values were significantly higher in patients with NGT than in patients with DM (13.58±11.08 ms versus 8.09±4.72 ms, P<0.0001). Receiver operator characteristic (ROC) analysis showed that a global pancreas T2*<13.73 ms was the optimal cutoff for predicting an abnormal OGTT, with an area under the curve (AUC) of 0.62. Global pancreas T2* values showed a weak significant correlation with insulin values (R=0.160; P=0.002) and homeostasis model assessment-insulin resistance (HOMA-IR) index (R=0.122; P=0.019). Conclusion. A normal global pancreas T2* value has a negative predictive value of 100% for IGT and DM. The low specificity of pancreatic iron overload for glucose dysregulation seems to support the hypothesis that a latency time is need before pancreatic iron burden could give impaired glucose tolerance and overt diabetes mellitus. Figure 1 Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

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Type 2 diabetes and impaired glucose tolerance in European children and adolescents with obesity -- a problem that is no longer restricted to minority groups

Acta Endocrinologica ◽

10.1530/eje.0.1510199 ◽

2004 ◽

pp. 199-206 ◽

Cited By ~ 125

Author(s):

S Wiegand ◽

U Maikowski ◽

O Blankenstein ◽

H Biebermann ◽

P Tarnow ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Children And Adolescents ◽

Fasting Glucose ◽

Sensitivity Index ◽

Model Assessment ◽

Abnormal Glucose Tolerance

BACKGROUND: The incidence of childhood obesity and type 2 diabetes is an increasing problem in Europe. We determined the prevalence of impaired glucose regulation in a predominantly Caucasian cohort of 491 children and adolescents with obesity. METHODS: Fasting glucose and insulin levels were determined in all 491 subjects. Patients with an abnormal fasting glucose or with additional risk factors (positive family history of type 2 diabetes, acanthosis nigricans, hyperlipidemia; n=102) underwent an oral glucose tolerance test (OGTT; 1.75 g glucose/kg body weight). Homeostasis model assessment was used to estimate insulin resistance in all subjects. The insulin sensitivity index was determined in those subjects who underwent an OGTT. Screening for mutations in the melanocortin 4 receptor (MC4R) gene and the coding region of the brain-derived neutrophic factor (BDNF) in 37 patients with an impaired glucose tolerance was performed by WAVE analysis. RESULTS: Out of the total of 491 patients, 12 had an abnormal fasting glucose level. Of the 102 patients who underwent an OGTT, 37 had impaired glucose tolerance; 6 out of the 102 patients were diagnosed with type 2 diabetes. Eighty-eight per cent of patients with abnormal glucose tolerance and 66% of patients with type 2 diabetes were Caucasian. Insulin resistance indices correlated well with the degree of abnormal glucose tolerance. Using the screening algorithm for type 2 diabetes as advocated by the American Diabetes Association, 68% of patients with impaired glucose tolerance and 66% of patients with type 2 diabetes would have been missed. No abnormalities in the MC4R and BDNF genes were detected. CONCLUSIONS: Impaired glucose tolerance and type 2 diabetes are far more common in obese European children of Caucasian origin than previously thought. Using fasting glucose levels as the main screening tool appears to be insufficient in detecting these children.

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Peripheric Metabolic Abnormalities in Schizophrenia Patients

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1549 ◽

2017 ◽

Vol 41 (S1) ◽

pp. s802-s802

Author(s):

M. Amorim ◽

A. Moreira ◽

A. Marques ◽

T. Summavielle

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Fasting Blood Glucose ◽

Disease Onset ◽

First Episode ◽

Metabolic Abnormalities ◽

Metabolic Disturbances ◽

Antipsychotic Therapy ◽

Glucose Levels ◽

Drug Naïve

IntroductionSchizophrenia (SCZ) is frequently associated with metabolic symptoms including dyslipidaemia, hyperinsulinemia, type 2 diabetes and obesity. In fact, SCZ patients have been reported to present higher prevalence of these conditions than general population, commonly associated to second generation antipsychotic therapy. Recent studies, however, have demonstrated that peripheral metabolic disturbances can appear at disease onset or drug-naïve patients.Objectives/aimsTo assess metabolic disturbances in first episode and/or drug-naïve SCZ patients.MethodsWe conducted a literature review through Pubmed search for MeSH: schizophrenia, metabolism, glucose, insulin. Controlled studies on first episode and/or drug-naïve SCZ patients were included.ResultsSeveral studies showed no change in SCZ patients’ fasting blood glucose, while others found increased glucose levels and impaired glucose tolerance in SCZ patients compared to healthy controls in several recent studies. Hyperinsulinemia and insulin resistance have also been identified in antipsychotic-naïve SCZ patients and it has been suggested that early onset patients are more likely to present insulin resistance. In addition, there's evidence of increased circulating levels of chromogranin A, pancreatic polypeptide, prolactin, cortisol, progesterone, thus emphasising that multiple components of the hypothalamic-pituitary-adrenal-gonadal axis may be affected in SCZ. These elevations were associated to normal glycaemia suggesting there may be insulin intolerance during early stages of SCZ, requiring an increased secretion from pancreatic Bcells to maintain normal glucose levels.ConclusionsRecent studies of first onset and/or drug-free schizophrenia patients have shown impaired fasting glucose tolerance, hyperinsulinemia and insulin intolerance, suggesting that metabolic abnormalities may play a role in SCZ onset and pathophysiology.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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