Displaying publications 141 - 160 of 643 in total

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  1. Syukri Y, Taher M, Martien R, Lukitaningsih E, Nugroho AE, Zakaria ZA
    Adv Pharm Bull, 2021 Jan;11(1):171-180.
    PMID: 33747864 DOI: 10.34172/apb.2021.018
    Purpose:
    Insulin resistance is a characteristic of non-insulin-dependent diabetes mellitus associated with obesity and caused by the failure of pancreatic beta cells to secrete sufficient amount of insulin. Andrographolide (AND) improves beta-cell reconstruction and inhibits fat-cell formation. This research aimed to improve the delivery of water-insoluble AND in self-nanoemulsifying (ASNE) formulation, tested in streptozotocin (STZ)-induced diabetic rats and 3T3-L1 preadipocyte cells.
    Methods:
    A conventional formulation of AND in suspension was used as a control. The experimental rats were orally administered with self-nanoemulsifying (SNE) and suspension of AND for 8 days. Measurements were performed to evaluate blood glucose levels in preprandial and postprandial conditions. Immunohistochemistry was used to assess the process of islet beta cell reconstruction. In vitro study was performed using cell viability and adipocyte differentiation assay to determine the delivery of AND in the formulation.
    Results:
    ASNE lowered blood glucose levels (day 4) faster than AND suspension (day 6). The histological testing showed that ASNE could regenerate pancreatic beta cells. Therefore, ASNE ameliorated pancreatic beta cells. The in vitro evaluation indicated the inhibition of adipocyte differentiation by both AND and ASNE, which occurred in a time-dependent manner. ASNE formulation had better delivery than AND.
    Conclusion:
    ASNE could improve the antidiabetic activity by lowering blood glucose levels, enhancing pancreatic beta cells, and inhibiting lipid formation in adipocyte cells.
    Matched MeSH terms: Insulin; Insulin Resistance; Insulin-Secreting Cells
  2. Chua GHI, Phang SCW, Wong YO, Ho LS, Palanisamy UD, Abdul Kadir K
    Nutrients, 2020 Nov 27;12(12).
    PMID: 33261162 DOI: 10.3390/nu12123659
    Malaysian national morbidity surveys on diabetic prevalence have shown ethnical variation among prediabetic and diabetic populations. In our attempt to understand this variation, we studied the α-tocopherol, insulin resistance, β-cell function and receptor of advanced glycation end-products (RAGE) levels, as risk factors of type 2 diabetes, among the different ethnicities. In total, 299 subjects of Malay, Chinese, Indian and aboriginal Orang Asli (OA) heritage were recruited from urban and rural areas of Malaysia by stratified random sampling. Serum α-tocopherol concentrations were measured using high performance liquid chromatography (HPLC) and insulin concentrations were measured using enzyme-linked immunosorbent assay (ELISA). In subjects with pre-diabetes, OAs had the highest α-tocopherol level, followed by Chinese and Malays (0.8938, 0.8564 and 0.6948 respectively; p < 0.05). In diabetic subjects, Malays had significantly higher RAGE levels compared to Chinese and Indians (5579.31, 3473.40 and 3279.52 pg/mL respectively, p = 0.001). Low α-tocopherol level (OR = 3.021, p < 0.05) and high insulin resistance (OR = 2.423, p < 0.05) were linked strongly to the development of pre-diabetes. Low β-cell function (OR = 5.657, p < 0.001) and high RAGE level (OR = 3.244, p < 0.05) were linked strongly to the development of diabetes from pre-diabetes. These factors might be involved in the development of diabetes, along with genetic and environmental factors.
    Matched MeSH terms: Hyperinsulinism; Insulin; Insulin Resistance; Insulin, Regular, Human
  3. Zaman R, Karim ME, Othman I, Zaini A, Chowdhury EH
    Pharmaceutics, 2020 Jul 29;12(8).
    PMID: 32751231 DOI: 10.3390/pharmaceutics12080710
    Oral delivery is considered as the most preferred and yet most challenging mode of drug administration; especially a fragile and sensitive peptide like insulin that shows extremely low bioavailability through the gastro-intestinal (GIT) route. To address this problem, we have designed a novel drug delivery system (DDS) using precipitation-induced Barium (Ba) salt particles. The DDS can load insulin molecules and transport them through the GIT route. There were several in vitro simulation tests carried out to prove the efficiency of Ba salt particles as oral delivery candidates. All three Ba salt particles (BaSO4, BaSO3, and BaCO3) showed very good loading of insulin (>70% in all formulations) and a degree of resistance throughout a wide range of pHs from basic to acidic conditions when assessed by spectrophotometry. Particles and insulin-associated particles were morphologically assessed and characterized using FE-SEM and FT-IR. A set of tests were designed and carried out with mucin to predict whether the particles are potentially capable of overcoming one of the barriers for crossing intestinal epithelium. The mucin binding experiment demonstrated 60-100% of mucin adhesion to the three different particles. FT-IR identifies the characteristic peaks for mucin protein, particles, and particle-mucin complex re-confirming mucin adhesion to the particles. Finally, the effectiveness of nano-insulin was tested on streptozotocin (STZ) induced diabetic rats. A short acting human insulin analog, insulin aspart, was loaded into Ba salt particles at a dose of 100 IU/Kg prior to oral administration. Among the three formulations, insulin aspart-loaded BaSO4 and BaCO3 particles dramatically reduced the existing hyperglycemia. BaSO4 with loaded Insulin showed an onset of glucose-lowering action within 1 hr, with blood glucose level measured significantly lower compared to the 2nd and 3rd h (p < 0.05). Insulin-loaded BaCO3 particles showed a significant decrease in blood glucose level at 1-2 h, although the glucose level started to show a slight rise at 3rd h and by 4th h, it was back to baseline level. However, although BaSO3 particles with loaded insulin showed a trend of reduction in blood glucose level, the reduction was not found to be significant (p < 0.05) at any point in time. Therefore, oral formulations of insulin/BaSO4 and insulin/BaCO3 particles were observed as effective as native insulin aspart subcutaneous formulation in terms of onset and duration of action. Further investigation will be needed to reveal bioavailability and mechanism of action of this novel Nano-Insulin formulations.
    Matched MeSH terms: Insulin; Insulin Aspart; Insulin, Regular, Human
  4. Jun TJ, Jelani AM, Omar J, Rahim RA, Yaacob NM
    Indian J Endocrinol Metab, 2020 04 30;24(2):191-195.
    PMID: 32699789 DOI: 10.4103/ijem.IJEM_305_19
    Objectives: This study was done to estimate serum anti-Müllerian hormone (AMH) level in polycystic ovary syndrome (PCOS) patients and to correlate serum AMH level with insulin resistance, lipid profile, and adiponectin levels.

    Materials and Methods: A cross-sectional study was conducted at Hospital Universiti Sains Malaysia (Hospital USM), Health Campus, Kubang Kerian, Kelantan, Malaysia. Thirty newly diagnosed patients with PCOS attending gynecology clinic between July 2016 and April 2017 were recruited. Fasting venous blood samples were collected from the subjects. Serum AMH, insulin, adiponectin, triglycerides, high-density lipoprotein cholesterol (HDL-C), and plasma glucose levels were measured, and insulin resistance was calculated based on homeostasis model of assessment-insulin resistance (HOMA-IR). The serum AMH level was estimated, and the correlation of serum AMH level with the metabolic parameters was analyzed.

    Results: The median of serum AMH levels in women with PCOS was 6.8 ng/mL (interquartile range: 7.38 ng/mL). There was a significant negative correlation between serum AMH and HOMA-IR or triglyceride levels (r = -0.49, P = 0.006 and r = -0.55, P = 0.002, respectively). A significant positive correlation was observed between serum AMH and serum HDL-C or serum adiponectin levels (r = 0.56, P = 0.001 and r = 0.44, P = 0.014, respectively) in all study subjects.

    Conclusion: The serum AMH level is associated with HOMA-IR, triglycerides, HDL-C, and adiponectin levels, and hence it may be used as a potential cardiometabolic risk marker in women with PCOS.

    Matched MeSH terms: Insulin; Insulin Resistance; Insulin, Regular, Human
  5. Aamir K., Khan H., Arya A.
    MyJurnal
    Introduction: Polymetabolic syndrome is a malady encompassing centralized accumulation of lipids and subsequent resistance to insulin leading towards diabesity. Currently, this condition is perilous threat to public health and also, creating perplexity for medical scientists. There is an intensive need for the development of obese rodent model having close resemblance with human metabolic syndrome (MetS); so that intricate molecular and/or therapeutic
    targets can be elucidated. The resultant simulations will be beneficial to explicate not only pathogenesis but also secret conversation of signaling pathways in inducing MetS related complications in other organs. Methods: Currently, there are different methods for the development of rodent models of MetS, for instance, utilizing high lipogenic diet, genetic alterations, induction by chemicals or by combination of high fat diet and few others. In general, combination of cafeteria or western diet and low dose of streptozotocin (STZ) is a fine example of diet induced experimental model. In this model animals are allowed free access to highly palatable, energy dense, unhealthy human food for 12-18 weeks which promotes voluntary hyperphagia resulting in weight gain, increased fat mass and insulin resistance. At the end of feeding period 30mg/kg STZ is given intraperitoneally to mimic human type 2 diabetic condition.
    Conclusion: Consumption of cafeteria diet with low dose STZ is considered to be the robust model of diabesity offering an exceptional stage to investigate the genomic, molecular, biochemical and cellular mechanisms of obesity and type 2 diabetes.
    Matched MeSH terms: Insulin; Insulin Resistance; Insulin, Regular, Human
  6. Benchoula K, Parhar IS, Wong EH
    Arch Biochem Biophys, 2021 Feb 15;698:108743.
    PMID: 33382998 DOI: 10.1016/j.abb.2020.108743
    Hyperglycaemia causes pancreatic β-cells to release insulin that then attaches to a specific expression of receptor isoform and reverses high glucose concentrations. It is well known that insulin is capable of initiating insulin-receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling pathways in target cells; such as liver, adipose tissues, and muscles. However, recent discoveries indicate that many other pathways, such as the Hedgehog (Hh) and growth factor-stimulating Wingless-related integration (Wnt) signaling pathways; are activated in hyperglycaemia as well. Although these two pathways are traditionally thought to have a decisive role in cellular growth and differentiation only, recent reports show that they are involved in regulating cellular homeostasis and energy balance. While insulin-activated IRS/PI3K/PKB pathway cascades are primarily known to reduce glucose production, it was recently discovered to increase the Hh signaling pathway's stability, thereby activating the PI3K/PKB/mammalian target of rapamycin complex 2 (mTORC2) signaling pathway. The Hh signaling pathway not only plays a role in lipid metabolism, insulin sensitivity, inflammatory response, diabetes-related complications, but crosstalks with the Wnt signaling pathway resulting in improved insulin sensitivity and decrease inflammatory response in diabetes.
    Matched MeSH terms: Insulin; Insulin Resistance; Insulin Receptor Substrate Proteins
  7. Chew YH, Shia YL, Lee CT, Majid FA, Chua LS, Sarmidi MR, et al.
    Mol Cell Endocrinol, 2009 Aug 13;307(1-2):57-67.
    PMID: 19524127 DOI: 10.1016/j.mce.2009.03.005
    A mathematical model to describe the oscillatory bursting activity of pancreatic beta-cells is combined with a model of glucose regulation system in this work to study the bursting pattern under regulated extracellular glucose stimulation. The bursting electrical activity in beta-cells is crucial for the release of insulin, which acts to regulate the blood glucose level. Different types of bursting pattern have been observed experimentally in glucose-stimulated islets both in vivo and in vitro, and the variations in these patterns have been linked to changes in glucose level. The combined model in this study enables us to have a deeper understanding on the regime change of bursting pattern when glucose level changes due to hormonal regulation, especially in the postprandial state. This is especially important as the oscillatory components of electrical activity play significant physiological roles in insulin secretion and some components have been found to be lost in type 2 diabetic patients.
    Matched MeSH terms: Insulin-Secreting Cells/drug effects*; Insulin-Secreting Cells/metabolism*
  8. Geeta Appannah, Nor Aishah Emi, Nur Athira Ahmad Yusin, Wan Ying Gan, Zalilah Mohd Shariff, Nurainul Hana Shamsuddin, et al.
    MyJurnal
    Introduction: This cross-sectional study aimed to investigate relationships between diet quality assessed by Malay- sian Healthy Eating Index (HEI) and cardiometabolic risk factors in adolescents aged 13 years. Methods: 336 ado- lescents from various public secondary schools provided information on sociodemography and their anthropometric measurements including height (cm), weight (kg) and waist circumference (cm) were measured. Body mass index (BMI) was estimated thereafter. Dietary intakes assessed using a validated adolescent food frequency questionnaire (FFQ) was used to estimate Malaysian HEI. Biomarker parameters including lipid profile, fasting glucose, insulin and insulin resistance were also assessed. Associations of diet quality indicators to cardiometabolic risk factors were examined using regression models. Results: The overall diet quality of the adolescents was rather poor (49%), with a greater percentage of males were found to have low dietary quality score compared to females (56% vs. 39%; p
    Matched MeSH terms: Insulin; Insulin Resistance; Insulin, Regular, Human
  9. Ahmad Z, Rasouli M, Azman AZ, Omar AR
    BMC Biotechnol, 2012 Sep 19;12:64.
    PMID: 22989329 DOI: 10.1186/1472-6750-12-64
    BACKGROUND: Gene therapy could provide an effective treatment of diabetes. Previous studies have investigated the potential for several cell and tissue types to produce mature and active insulin. Gut K and L-cells could be potential candidate hosts for gene therapy because of their special features.

    RESULTS: In this study, we isolated gut K and L-cells to compare the potential of both cell types to produce insulin when exposed to similar conditions. The isolated pure K and L-cells were transfected with recombinant plasmids encoding insulin and with specific promoters for K or L-cells. Insulin expression was studied in response to glucose or meat hydrolysate. We found that glucose and meat hydrolysate efficiently induced insulin secretion from K and L-cells. However, the effects of meat hydrolysate on insulin secretion were more potent in both cells compared with glucose. Results of enzyme-linked immunosorbent assays showed that L-cells secreted more insulin compared with K-cells regardless of the stimulator, although this difference was not statistically significant.

    CONCLUSION: The responses of K and L-cells to stimulation with glucose or meat hydrolysate were generally comparable. Therefore, both K and L-cells show similar potential to be used as surrogate cells for insulin gene expression in vitro. The potential use of these cells for diabetic gene therapy warrants further investigation.

    Matched MeSH terms: Insulin/genetics*; Insulin/metabolism*
  10. Christinal Teh Pey Wen, Nurul Adibah Nizam, Abdul Rahman Jamal, Wan Zurinah Wan Ngah, Chong, Pei Nee, Poh, Bee Koon
    MyJurnal
    Childhood obesity is a global epidemic, which leads to the increasing number of studies on genetic locations associated with obesity-related traits. Polymorphisms of insulin (INS) gene have been shown to be associated with obesity-related phenotypes in Europeans; while insulin receptor (INSR) gene has been associated with energy regulation. Therefore, this study was conducted to investigate the association between the INS (rs689) and INSR (rs3745551) gene polymorphisms with childhood obesity risk in a Malay childhood population. Normal weight (538) and overweight or obese (557) children aged 6-12 years old were genotyped using semi-automated Sequenom iPLEX® Gold. Body mass index (BMI) was calculated from measured body weight and height. The rs689 (T/T: 0.006, A/T: 0.159 and A/A: 0.835) and rs3745551 (G/G: 0.054, A/G: 0.378 and A/A: 0.568) genotype distributions were consistent with Hardy Weinberg equilibrium. The T-minor allele frequency for rs689 was 8.6% and G-minor allele frequency for rs3745551 was 24.3%. Minor allele of INS gene polymorphisms significantly increased risk of obesity among Malay children (sex- and age-adjusted
    OR=1.580; 95%CI: 1.134-2.201). However, INSR gene polymorphisms were not significantly associated with childhood obesity. In conclusion, the polymorphisms of INS gene, rather than INSR gene, were associated with childhood obesity in the Malay population.
    Matched MeSH terms: Insulin-Like Growth Factor I; Receptor, Insulin; Insulin-Like Growth Factor Binding Protein 3
  11. Chang LF, Vethakkan SR, Nesaretnam K, Sanders TA, Teng KT
    J Clin Lipidol, 2016 09 17;10(6):1431-1441.e1.
    PMID: 27919361 DOI: 10.1016/j.jacl.2016.09.006
    BACKGROUND: Current dietary guidelines recommend the replacement of saturated fatty acids (SAFAs) with carbohydrates or monounsaturated fatty acids (MUFAs) based on evidence on lipid profile alone, the chronic effects of the mentioned replacements on insulin secretion and insulin sensitivity are however unclear.

    OBJECTIVE: To assess the chronic effects of the substitution of refined carbohydrate or MUFA for SAFA on insulin secretion and insulin sensitivity in centrally obese subjects.

    METHODS: Using a crossover design, randomized controlled trial in abdominally overweight men and women, we compared the effects of substitution of 7% energy as carbohydrate or MUFA for SAFA for a period of 6 weeks each. Fasting and postprandial blood samples in response to corresponding SAFA, carbohydrate, or MUFA-enriched meal-challenges were collected after 6 weeks on each diet treatment for the assessment of outcomes.

    RESULTS: As expected, postprandial nonesterified fatty acid suppression and elevation of C-peptide, insulin and glucose secretion were the greatest with high-carbohydrate (CARB) meal. Interestingly, CARB meal attenuated postprandial insulin secretion corrected for glucose response; however, the insulin sensitivity and disposition index were not affected. SAFA and MUFA had similar effects on all markers except for fasting glucose-dependent insulinotropic peptide concentrations, which increased after MUFA but not SAFA when compared with CARB.

    CONCLUSION: In conclusion, a 6-week lower-fat/higher-carbohydrate (increased by 7% refined carbohydrate) diet may have greater adverse effect on insulin secretion corrected for glucose compared with isocaloric higher-fat diets. In contrast, exchanging MUFA for SAFA at 7% energy had no appreciable adverse impact on insulin secretion.

    Matched MeSH terms: Insulin/blood*; Insulin Resistance
  12. Yang X, Kord-Varkaneh H, Talaei S, Clark CCT, Zanghelini F, Tan SC, et al.
    Pharmacol Res, 2020 01;151:104588.
    PMID: 31816435 DOI: 10.1016/j.phrs.2019.104588
    BACKGROUND: A meta-analysis is needed to comprehensively consolidate findings from the influence of metformin on IGF-1 levels. The present study was conducted with the objective to accurately evaluate the influence of metformin intake on IGF-1 levels via a meta-analysis of randomized controlled trials.

    METHODS: A comprehensive systematic search was carried out in PubMed/MEDLINE, Web of Science, SCOPUS and Embase from inception until June 2019. Weighted mean difference (WMD) with the 95 % CI were applied for estimating the effects of metformin on serum IGF-1 levels.

    RESULTS: 11 studies involving a total of 569 individuals reported changes in IGF-1 plasma concentrations as an outcome measure. Pooled results demonstrated an overall non-significant decline in IGF-1 following metformin intake (WMD: -8.292 ng/ml, 95 % CI: -20.248, 3.664, p = 0.174) with heterogeneity among (p = 0.000,I2 = 87.1 %). The subgroup analyses displayed that intervention duration <12 weeks on children (WMD:-55.402 ng/ml, 95 % CI: -79.845, -30.960, I2 = 0.0 %) significantly reduced IGF-1. Moreover, in age 18 < years older metformin intake (WMD: 15.125 ng/ml, 95 % CI: 5.522, 24.729, I2 = 92.5 %) significantly increased IGF-1 than 18 ≤ years older (WMD:-1.038 ng/ml, 95 % CI: -3.578,1.502,I2 = 78.0 %). Following dose-response evaluation, metformin intake reduced IGF-1 (coefficient for dose-response analysis= -13.14, P = 0.041 and coefficient for liner analysis= -0.066, P = 0.038) significantly based on treatment duration.

    CONCLUSION: We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1. We suggest that caution be taken when interpreting the findings of this review, particularly given the discordant supplementation practices between children and adults.

    Matched MeSH terms: Insulin-Like Growth Factor I/analysis*; Insulin-Like Growth Factor I/metabolism
  13. Irfan HM, Khan NAK, Asmawi MZ
    Arch Physiol Biochem, 2020 May 15.
    PMID: 32412306 DOI: 10.1080/13813455.2020.1762661
    Background:Moringa oleifera Lam. has been used traditionally for the treatment of different cardio-metabolic disorders. So, the aim was to assess its leaf extracts in metabolic syndrome rat model.Methods: Out of the total 36-rats, 6 rats were given normal matched diet (NMD) while the rest were provided high-fat diet and 20% fructose (HFD-20%F). Moringa oleifera leaf extracts were administered orally for 30 days. Body weight, blood glucose, BMI, blood pressure, lipids, insulin, insulin resistance, MCP-1, visceral fat and liver weight were evaluated.Results: Sixty-days feeding with HFD-20%F produced the metabolic syndrome features like hyperinsulinemia, insulin resistance, and increase in low-density lipoprotein (LDL), visceral fat, and liver weight significantly (p
    Matched MeSH terms: Hyperinsulinism; Insulin; Insulin Resistance; Insulin, Regular, Human
  14. Fulcher GR, Jarlov H, Piltoft JS, Singh KP, Liu L, Mohamed M, et al.
    Endocrine, 2021 12;74(3):530-537.
    PMID: 34637072 DOI: 10.1007/s12020-021-02887-8
    PURPOSE: IDegAsp, a co-formulation of long-acting basal (insulin degludec) and rapid-acting bolus (insulin aspart) insulin, provides separate prandial and basal glucose-lowering effects with relatively low risk of hypoglycaemia. Its efficacy and safety have been investigated in a large clinical trial programme (BOOST). We present the rationale and design of the ARISE study, which aims to assess glycaemic control and other clinical parameters associated with IDegAsp use in real world.

    METHODS: ARISE is a ~26-wk-long, prospective, non-interventional, single-arm study of patients with type 2 diabetes (T2D) initiating IDegAsp treatment. Approximately 1112 patients with T2D aged ≥18 years previously on anti-hyperglycaemic drugs except IDegAsp will be enroled across six countries from 15 Aug 2019 to 12 Nov 2020. IDegAsp treatment will be initiated at the physicians' discretion and as per the local label. Key exclusion criteria include previous participation, or previous IDegAsp treatment. The primary and secondary endpoints are change in HbA1c from baseline (wk 0) to study end (wk 26-36) and the proportion of patients achieving the target HbA1c level of <7% at the study end, respectively. A mixed model for repeated measurements will analyse the primary endpoint.

    CONCLUSION: Between-country differences in the prescription patterns of glucose-lowering agents in people with T2D warrant examination of their clinical use in different geographical settings. The ARISE study is designed to assess the clinical use of IDegAsp from real world in six different countries. Findings from the ARISE study will supplement those of previous randomised controlled studies by establishing real-world evidence of IDegAsp use in the participating countries.

    TRIAL REGISTRATION: ClinicalTrials.gov, NCT04042441. Registered 02 August 2014, https://clinicaltrials.gov/ct2/show/NCT04042441.

    Matched MeSH terms: Insulin, Long-Acting; Insulin Aspart*
  15. Mathiesen ER, Ali N, Alibegovic AC, Anastasiou E, Cypryk K, de Valk H, et al.
    Diabetes Care, 2021 09;44(9):2069-2077.
    PMID: 34330786 DOI: 10.2337/dc21-0472
    OBJECTIVE: To compare the risk of severe adverse pregnancy complications in women with preexisting diabetes.

    RESEARCH DESIGN AND METHODS: Multinational, prospective cohort study to assess the prevalence of newborns free from major congenital malformations or perinatal or neonatal death (primary end point) following treatment with insulin detemir (detemir) versus other basal insulins.

    RESULTS: Of 1,457 women included, 727 received detemir and 730 received other basal insulins. The prevalence of newborns free from major congenital malformations or perinatal or neonatal death was similar between detemir (97.0%) and other basal insulins (95.5%) (crude risk difference 0.015 [95% CI -0.01, 0.04]; adjusted risk difference -0.003 [95% CI -0.03, 0.03]). The crude prevalence of one or more congenital malformations (major plus minor) was 9.4% vs. 12.6%, with a similar risk difference before (-0.032 [95% CI -0.064, 0.000]) and after (-0.036 [95% CI -0.081, 0.009]) adjustment for confounders. Crude data showed lower maternal HbA1c during the first trimester (6.5% vs. 6.7% [48 vs. 50 mmol/mol]; estimated mean difference -0.181 [95% CI -0.300, -0.062]) and the second trimester (6.1% vs. 6.3% [43 vs. 45 mmol/mol]; -0.139 [95% CI -0.232, -0.046]) and a lower prevalence of major hypoglycemia (6.0% vs. 9.0%; risk difference -0.030 [95% CI -0.058, -0.002]), preeclampsia (6.4% vs. 10.0%; -0.036 [95% CI -0.064, -0.007]), and stillbirth (0.4% vs. 1.8%; -0.013 [95% CI -0.024, -0.002]) with detemir compared with other basal insulins. However, differences were not significant postadjustment.

    CONCLUSIONS: Insulin detemir was associated with a similar risk to other basal insulins of major congenital malformations, perinatal or neonatal death, hypoglycemia, preeclampsia, and stillbirth.

    Matched MeSH terms: Insulin Detemir/adverse effects; Insulin, Long-Acting
  16. Asghar A, Firasat S, Afshan K, Naz S
    Mol Biol Rep, 2023 Jan;50(1):57-64.
    PMID: 36301463 DOI: 10.1007/s11033-022-08011-x
    BACKGROUND: CDK5 regulatory subunit associated protein 1 like 1 (CDKAL1) encodes a tRNA modifying enzyme involved in the proper protein translation and regulation of insulin production encoded by the CDKL gene. Sequence variations in the CDKAL1 gene lead to the misreading of the Lys codon in proinsulin, resulting in decreased glucose-stimulated proinsulin production. Various polymorphic sequence variants of the CDKAL1 gene such as rs7754840, rs7756992, rs9465871, and rs10946398 are reported to be associated with type 2 diabetes mellitus and gestational diabetes mellitus (GDM) incidence. One of these single nucleotide polymorphisms i.e., rs10946398 has been reported to impact the risk of GDM and its outcomes in pregnant women of different ethnicities i.e., Egypt, Chinese, Korean, Indian, Arab, and Malaysian. Numerous findings have shown that rs10946398 overturns the regulation of CDKAL1 expression, resulting in decreased insulin production and elevated risk of GDM. However, there is no data regarding rs10946398 genotype association with GDM incidence in our population.

    METHODOLOGY: In this study, 47 GDM patients and 40 age-matched controls were genotyped for rs10946398 CDKAL1 variant using Tetra primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra ARMS-PCR).

    RESULTS: Analysis of the results showed the significant association of the C allele of CDKAL1 SNP rs10946398 (χ2 = 0.02 p = 0.001) with the risk of GDM development. Conclusively, the results support the role of SNP i.e., rs10946398 of CDKAL1 gene in GDM development in Pakistani female patients. However, future large-scale studies are needed to functionally authenticate the role of variant genotypes in the disease pathogenesis and progression.

    Matched MeSH terms: Insulin/genetics; Insulin/metabolism; Proinsulin/genetics
  17. Mohammadi S, Asbaghi O, Dolatshahi S, Omran HS, Amirani N, Koozehkanani FJ, et al.
    Nutr J, 2023 Oct 06;22(1):49.
    PMID: 37798798 DOI: 10.1186/s12937-023-00878-1
    BACKGROUND: It is suggested that supplementation with milk protein (MP) has the potential to ameliorate the glycemic profile; however, the exact impact and certainty of the findings have yet to be evaluated. This systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) assessed the impact of MP supplementation on the glycemic parameters in adults.

    METHODS: A systematic search was carried out among online databases to determine eligible RCTs published up to November 2022. A random-effects model was performed for the meta-analysis.

    RESULTS: A total of 36 RCTs with 1851 participants were included in the pooled analysis. It was displayed that supplementation with MP effectively reduced levels of fasting blood glucose (FBG) (weighted mean difference (WMD): -1.83 mg/dL, 95% CI: -3.28, -0.38; P = 0.013), fasting insulin (WMD: -1.06 uU/mL, 95% CI: -1.76, -0.36; P = 0.003), and homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: -0.27, 95% CI: -0.40, -0.14; P  8 weeks) with high or moderate doses (≥ 60 or 30-60 g/d) of MP or whey protein (WP). Serum FBG levels were considerably reduced upon short-term administration of a low daily dose of WP (insulin were remarkably decreased during long-term supplementation with high or moderate daily doses of WP.

    CONCLUSION: The findings of this study suggest that supplementation with MP may improve glycemic control in adults by reducing the values of fasting insulin, FBG, and HOMA-IR. Additional trials with longer durations are required to confirm these findings.

    Matched MeSH terms: Insulin; Insulin Resistance*
  18. Jamaludin UK, Docherty PD, Geoffrey Chase J, Shaw GM
    J Med Biol Eng, 2015 02 03;35(1):125-133.
    PMID: 25750607
    Critically ill patients are occasionally associated with an abrupt decline in renal function secondary to their primary diagnosis. The effect and impact of haemodialysis (HD) on insulin kinetics and endogenous insulin secretion in critically ill patients remains unclear. This study investigates the insulin kinetics of patients with severe acute kidney injury (AKI) who required HD treatment and glycaemic control (GC). Evidence shows that tight GC benefits the onset and progression of renal involvement in precocious phases of diabetic nephropathy for type 2 diabetes. The main objective of GC is to reduce hyperglycaemia while determining insulin sensitivity. Insulin sensitivity (S
    I
    ) is defined as the body response to the effects of insulin by lowering blood glucose levels. Particularly, this study used S
    I
    to track changes in insulin levels during HD therapy. Model-based insulin sensitivity profiles were identified for 51 critically ill patients with severe AKI on specialized relative insulin nutrition titration GC during intervals on HD (OFF/ON) and after HD (ON/OFF). The metabolic effects of HD were observed through changes in S
    I
    over the ON/OFF and OFF/ON transitions. Changes in model-based S
    I
    at the OFF/ON and ON/OFF transitions indicate changes in endogenous insulin secretion and/or changes in effective insulin clearance. Patients exhibited a median reduction of -29 % (interquartile range (IQR): [-58, 6 %], p = 0.02) in measured S
    I
    after the OFF/ON dialysis transition, and a median increase of +9 % (IQR -15 to 28 %, p = 0.7) after the ON/OFF transition. Almost 90 % of patients exhibited decreased S
    I
    at the OFF/ON transition, and 55 % exhibited increased S
    I
    at the ON/OFF transition. Results indicate that HD commencement has a significant effect on insulin pharmacokinetics at a cohort and per-patient level. These changes in metabolic behaviour are most likely caused by changes in insulin clearance or/and endogenous insulin secretion.
    Matched MeSH terms: Insulin; Insulin Resistance; Insulin, Regular, Human
  19. Loh HH, Lim LL, Loh HS, Yee A
    J Diabetes Investig, 2019 Nov;10(6):1490-1501.
    PMID: 30938074 DOI: 10.1111/jdi.13054
    AIMS/INTRODUCTION: Although patients with type 1 diabetes are medically exempt, many insist on fasting during Ramadan. Multiple daily insulin injections (MDI), premixed insulin and continuous subcutaneous insulin infusion (CSII) are commonly used. To date, little is known about the safety of Ramadan fasting in these patients.

    MATERIALS AND METHODS: We pooled data from 17 observational studies involving 1,699 patients treated with either CSII or non-CSII (including premixed and MDI) regimen. The study outcomes were the frequencies of hypoglycemia, hyperglycemia and/or ketosis. Given the lack of patient-level data, separate analyses for premixed and MDI regimen were not carried out.

    RESULTS: The CSII-treated group (n = 203) was older (22.9 ± 6.9 vs 17.8 ± 4.0 years), and had longer diabetes duration (116.7 ± 66.5 vs 74.8 ± 59.2 months) and lower glycated hemoglobin (7.8 ± 1.1% vs 9.1 ± 2.0%) at baseline than the non-CSII-treated group (n = 1,496). The non-CSII-treated group had less non-severe hypoglycemia than the CSII-treated group (22%, 95% CI 13-34 vs 35%, 95% CI 17-55). Of the non-CSII-treated group, 7.1% (95% CI 5.8-8.5) developed severe hypoglycemia, but none from the CSII-treated group did. The non-CSII-treated group was more likely to develop hyperglycemia (12%, 95% CI 3-25 vs 8.8%, 95% CI 0-31) and ketosis (2.5%, 95% CI 1.0-4.6 vs 1.6%, 95% CI 0.1-4.7), and discontinue fasting (55%, 95% CI 34-76 vs 31%, 95% CI 9-60) than the CSII-treated group.

    CONCLUSIONS: The CSII regimen had lower rates of severe hypoglycemia and hyperglycemia/ketosis, but a higher rate of non-severe hyperglycemia than premixed/MDI regimens. These suggest that appropriate patient selection with regular, supervised fine-tuning of the basal insulin rate with intensive glucose monitoring might mitigate the residual hypoglycemia risk during Ramadan.

    Matched MeSH terms: Insulin/administration & dosage*; Insulin Infusion Systems
  20. Safi SZ, Batumalaie K, Qvist R, Mohd Yusof K, Ismail IS
    PMID: 27034691 DOI: 10.1155/2016/5843615
    Purpose. Type 2 diabetes consists of progressive hyperglycemia and insulin resistance, which could result from glucose toxicity, inflammatory cytokines, and oxidative stress. In the present study we investigated the effect of Gelam honey and quercetin on the oxidative stress-induced inflammatory pathways and the proinflammatory cytokines. Methods. HIT-T15 cells were cultured and preincubated with the extract of Gelam honey (20, 40, 60, and 80 μg/mL), as well as quercetin (20, 40, 60, and 80 μM), prior to stimulation by 20 and 50 mM glucose. Results. HIT-T15 cells cultured under hyperglycemic condition showed a significant increase in the inflammatory pathways by phosphorylating JNK, IKK-β, and IRS-1 at Ser307 (p < 0.05). There was a significant decrease in the phosphorylation of Akt at Ser473 (p < 0.05). Pretreatment with Gelam honey and quercetin reduced the expression of phosphorylated JNK, IKK-β, and IRS-1, thereby significantly reducing the expression of proinflammatory cytokines like TNF-α, IL-6, and IL-1β (p < 0.05). At the same time there was a significant increase in the phosphorylated Akt showing the protective effects against inflammation and insulin resistance (p < 0.05). In conclusion, our data suggest the potential use of the extract from Gelam honey and quercetin in modulating the inflammation induced insulin signaling pathways.
    Matched MeSH terms: Insulin; Insulin Resistance; Insulin Receptor Substrate Proteins
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