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

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1751
Author(s):  
Saroj Khatiwada ◽  
Virginie Lecomte ◽  
Michael F. Fenech ◽  
Margaret J. Morris ◽  
Christopher A. Maloney

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.

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hui Wu ◽  
Michael Wu ◽  
Yi Chen ◽  
Carolyn A. Allan ◽  
David J. Phillips ◽  
...  

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.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Alexis Elias Malavazos ◽  
Emanuele Cereda ◽  
Federica Ermetici ◽  
Riccardo Caccialanza ◽  
Silvia Briganti ◽  
...  

“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.


2018 ◽  
Vol 15 (4) ◽  
pp. 294-301 ◽  
Author(s):  
Leila Hadjadj ◽  
Szabolcs Várbíró ◽  
Eszter Mária Horváth ◽  
Anna Monori-Kiss ◽  
Éva Pál ◽  
...  

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.


2015 ◽  
Vol 6 ◽  
pp. JCM.S32743 ◽  
Author(s):  
Hiroko Katayama ◽  
Daisuke Tachibana ◽  
Akihiro Hamuro ◽  
Takuya Misugi ◽  
Koka Motoyama ◽  
...  

Objective The aim of this study was to compare glucose intolerance in the antenatal and the postpartum periods using a 75-g oral glucose tolerance test (OGTT) in the Japanese women with gestational diabetes mellitus (GDM) using a retrospective design. Patients and Methods Data were obtained from 85 Japanese women with GDM who delivered from April 2011 through April 2015 and who underwent an OGTT 6–14 weeks postpartum. The women were divided into two groups based on the results of the postpartum OGTT: one group with normal glucose tolerance (NGT) and the other with impaired glucose tolerance (IGT) as well as impaired fasting glucose (IFG). We analyzed the associations between postpartum IGT–IFG and various factors. Results Antenatally, a significant difference was observed between the groups only in the 1-hour plasma glucose level of the 75-g OGTT. Postpartum results of plasma glucose level were significantly higher at 0.5, 1, and 2 hours in the IGT–IFG group than those in the NGT group. Moreover, a significant decrease in the levels of 0.5-hour immunoreactive insulin and insulinogenic index was observed in the IGT–IFG group compared to those in the NGT group. Homeostasis model assessment-insulin resistance and homeostasis model assessment β-cell function of both groups were found to significantly decrease in the postpartum period; however, there was no significant change in the insulinogenic index of either group. Conclusions Our study clearly showed that the postpartum IGT and IFG levels of Japanese women with GDM are affected by impaired early-phase insulin secretion; however, insulin resistance promptly improves.


2016 ◽  
Vol 46 (15) ◽  
pp. 3219-3230 ◽  
Author(s):  
D. C. Chen ◽  
X. D. Du ◽  
G. Z. Yin ◽  
K. B. Yang ◽  
Y. Nie ◽  
...  

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.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Yoshihiro Kokubo ◽  
Makoto Watanabe ◽  
Aya Higashiyama ◽  
Yoko M Nakao ◽  
Takashi Kobayashi ◽  
...  

Introduction: Glucose intolerance and insulin resistance are known risk factors for cardiovascular disease (CVD). However, few prospective studies were reported the association between combinations of these two factors and incident CVD. We assessed the hypothesis that insulin resistance increased the association between glucose intolerance and CVD in Japanese general population. Methods: We studied 4,638 Japanese individuals (mean age 56.1 years, without CVD) who completed a baseline medical examination and a 75g oral glucose tolerance test in the Suita Study. Glucose categories were defined as follows: diabetes mellitus (DM; fasting plasma glucose levels [FPG] ≥126 mg/dL, 2 hours post-loaded glucose levels [2h-PG] ≥ 200 mg/dL, and/or DM medication); impaired glucose tolerance (IGT; FPG <126 mg/dL and 2h-PG =140-199 mg/dL); impaired fasting glucose (IFG; FPG =100-125 mg/dL and 2h-PG <140 mg/dL); and normal glucose tolerance [NGT]. Insulin resistance was the following formula: HOMA-IR = [FPG] x [fasting insulin] / 405. Insulin resistance was defined as HOMA-IR ≥2.5. Multivariable-adjusted Cox proportional hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated after adjusting for age, sex, body mass index, blood pressure category, hyperlipidemia, smoking, and drinking at the baseline. Results: During the 11.7-year follow-up, we documented 127 cerebral infarctions, 63 hemorrhagic stroke, 12 unclassified strokes, and 143 coronary heart disease events. The adjusted HRs (95% CIs) of subjects with FPG =100-125 mg/dL and ≥126 mg/dL were 1.38 (1.01-1.89) and 2.00 (1.12-3.58) for stroke and 1.47 (0.99-2.19) and 2.73 (1.43-5.22) for cerebral infarction, respectively, compared with the fasting NGT group. On the basis of the subjects with 2h-PG <140 mg/dL group, the adjusted HRs (95% CIs) of subjects with 2h-PG ≥200 mg/dL were 1.71 (1.07-2.72) for stroke and 2.06 (1.20-3.54) for cerebral infarction. Compared to the NGT group, the adjusted HRs (95% CIs) of the subjects with IFG, IGT, and DM were 1.59 (1.10-2.30), 1.34 (0.89-2.00), and 1.86 (1.16-3.00) for stroke and 1.82 (1.13-2.90), 1.55 (0.93-2.56), and 2.43 (1.39-4.26) for cerebral infarction, respectively. Compared to the subjects with HOMA-IR <1.5, the adjusted HRs (95% CIs) of CVD and stroke with HOMA-IR ≥2.5 were 1.45 (1.07-1.96) and 1.61 (1.07-2.42), respectively. Compared to the NGT group without insulin resistance, the IFG and DM groups with insulin resistance were observed the increased risks of stroke (HRs [95% CIs]; 2.05 [1.17-3.57] and 2.11 [1.17-3.83]) and cerebral infarction (HRs [95% CIs]; 2.45 [1.20-5.00] and 3.56 [1.84-6.88]), respectively. Conclusions: Fasting glucose intolerance and insulin resistance are predictive factors for the incidence of stroke and cerebral infarction. Insulin resistance increased the risks of incident stroke and cerebral infarction in general inhabitants with IFG and DM.


2004 ◽  
pp. 199-206 ◽  
Author(s):  
S Wiegand ◽  
U Maikowski ◽  
O Blankenstein ◽  
H Biebermann ◽  
P Tarnow ◽  
...  

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.


2016 ◽  
Vol 102 (3) ◽  
pp. 801-809 ◽  
Author(s):  
Michael Quartuccio ◽  
Erica Hall ◽  
Vikesh Singh ◽  
Martin A. Makary ◽  
Kenzo Hirose ◽  
...  

Abstract Context: Total pancreatectomy with islet auto transplantation (TPIAT) is a treatment for medically refractory chronic pancreatitis that can prevent postsurgical diabetes in some patients. Predictors of insulin independence are needed for appropriate patient selection and counseling. Objective: To explore glycemic predictors of insulin independence after TPIAT. Design: A prospective cohort of patients. Methods: We investigated 34 patients undergoing TPIAT from 2011-2016 at Johns Hopkins Hospital, all had a 75-g oral glucose tolerance test (OGTT) administered prior to their TPIAT. The primary outcome was insulin independence 1 year after TPIAT. Results: Ten of 34 (29%) patients were insulin independent 1 year after TPIAT. All patients with impaired fasting glucose and/or impaired glucose tolerance preoperatively were insulin dependent at 1 year. In age-adjusted regression analyses, fasting glucose ≤ 90 mg/dL [odds ratio (OR) = 6.56; 1.11 to 38.91; P = 0.04], 1-hour OGTT glucose ≤ 143 mg/dL (OR = 6.65; 1.11 to 39.91; P = 0.04), and 2-hour OGTT glucose ≤ 106 mg/dL (OR = 11.74; 1.46 to 94.14; P = 0.02) were significant predictors of insulin independence. In receiver operating characteristic analyses, homeostatic model assessment of β-cell function (HOMA-β) was the most robust predictor of insulin independence [area under the curve (AUC) = 0.88; 0.73 to 1.00]. Conclusions: Normal preoperative glucose status and lower fasting and postchallenge OGTT glucose values are significant predictors of insulin independence after TPIAT. Higher islet function (HOMA-β) was the strongest predictor. OGTT testing may be a useful tool to aid in patient counseling prior to TPIAT and should be further investigated.


2006 ◽  
Vol 155 (1) ◽  
pp. 73-78 ◽  
Author(s):  
B Steffin ◽  
B Gutt ◽  
M Bidlingmaier ◽  
C Dieterle ◽  
F Oltmann ◽  
...  

Object: Treatment with somatostatin analogues (SA) not only inhibits GH secretion but may also impair insulin secretion. In order to evaluate the influence of SA on glucose metabolism, we investigated insulin resistance (IR) and β-cell function, using the recommended combination of homeostatic model assessment of IR (HOMA-IR) and β-cell function (HOMA-β). Design and methods: This is a prospective, cross-sectional study. We measured fasting insulin, blood glucose and IGF-I. Insulin and blood glucose measurements were taken 120 min after an oral glucose tolerance test with 75 g glucose. We studied 51 patients (27 female/24 male, age 54 years (20–75)). Eighteen patients were on Lanreotide Autogel (LA) treatment, 33 had no medical treatment. GH-levels of more than 2.5 ng/ml was reached by 59% of the patients, 74.5% had normal IGF-I levels. Results: We found no significant influence of disease activity on HOMA-IR and HOMA-β. In the 33 of 51 subjects without any drug treatment, median HOMA-β was 170.4% (36.0–624.0%). In contrast, in the 18 patients on LA treatment, median HOMA-β was found to be significantly lower (84.2% (36.5–346.2%); P = 0.001). Despite this, there was no difference in HOMA-IR in both groups (2.4 (0.7–8.4) vs 2.3 (0.7–6.1); P < 0.001) despite similar insulin values. Conclusion: In conclusion, we found that LA decreases β-cell function significantly without affecting IR. Therefore, we think that insulin secretagogues are probably more effective in the treatment of diabetes mellitus in acromegalic patients on LA therapy than insulin sensitizers.


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