Improvement In Fasting Plasma Glucose Research Articles

Low-dose IL-2 restores metabolic dysfunction and immune dysregulation in mice with type 2 diabetes induced by a high-fat, high-sugar diet and streptozotocin.

Interleukin-2 (IL-2) is pivotal in immune regulation, particularly in the promotion of regulatory T (Treg) cells and the maintenance of immune tolerance. While its efficacy in autoimmune diseases is well established, its role in type 2 diabetes (T2D) remains largely unexplored. This study investigates the effects of low-dose IL-2 in a KM mouse model of T2D induced by streptozotocin (STZ) and a high-fat, high-sugar (HFHS) diet. We found that low-dose IL-2 administration significantly improved fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) levels, and glucose tolerance, indicating better glycemic control. Additionally, IL-2 treatment improved insulin sensitivity, enhanced insulin secretion, and ameliorated lipid metabolism, as evidenced by reduced cholesterol and triglyceride levels. These metabolic improvements were associated with a modulation of inflammation, including a reduction in pro-inflammatory cytokines (TNF-α, IL-1β) and an increase in anti-inflammatory cytokines (IL-10). Importantly, IL-2 also altered the gut microbiome, reducing intestinal inflammation and endotoxin levels, which suggests a broader impact on metabolic health beyond immune regulation. These findings support the potential of low-dose IL-2 as an immunotherapeutic approach for improving metabolic dysfunction and inflammation in T2D.

Intense simplified strategy for newly diagnosed type 2 diabetes in patients with severe hyperglycaemia: multicentre, open label, randomised trial

ObjectiveTo evaluate whether the intense simplified strategy, which comprises short term intensive insulin therapy (SIIT) followed by subsequent oral antihyperglycaemic regimens, could improve long term glycaemic outcomes in patients with...

The effect of blood flow-restrictive resistance training on the risk of atherosclerotic cardiovascular disease in middle-aged patients with type 2 diabetes: a randomized controlled trial.

The aim of this study was to investigate the effects of blood flow-restrictive resistance training (BFR-RT) on improving metabolic abnormalities, blood pressure (BP), obesity, and 10-year atherosclerotic cardiovascular disease (ASCVD) risk in middle-aged patients with type 2 diabetes mellitus (T2DM). We conducted a parallel-group, single blind randomized controlled trial. Participants who met the inclusion criteria were randomly divided into control group, BFR-RT group and aerobic exercise (AE) group. Control group received health education and follow-up; Two exercise groups received supervised collective training for a period of six months, three times per week. AE group trained at moderate-intensity for 60 minutes each time, while BFR-RT group trained at low-intensity for 40 minutes each time. The primary outcomes were change in 10-year ASCVD risk index and level, and the secondary outcomes included changes in fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), blood lipids, BP, and obesity level within and across the three groups at baseline, the third and sixth months of intervention. Among 93 individuals (control group, n=31; AE, n=30; BFR-RT, n=32) were analyzed. At baseline, there were no significant differences in various indicators among the three groups (p>0.05). After intervention, the 10-year ASCVD risk index and risk level of both exercise groups significantly decreased compared to the control group and baseline (p<0.05), and the risk reduction became more pronounced over time. In the sixth month of intervention, the 10-year ASCVD risk index in the AE group decreased by 27.40%, and that in the BFR-RT group decreased by 26.78%. Meanwhile, apart from lipoprotein (a) and diastolic blood pressure, both exercise groups showed significant improvements in FPG, HbA1c, dyslipidemia, systolic blood pressure, and obesity indicators compared to the control group and baseline (p<0.05). There was no significant difference in various indicators between the two exercise groups (p>0.05). BFR-RT could reduce the 10-year ASCVD risk in middle-aged T2DM patients for by improving metabolic abnormalities, BP and obesity, and its effect was similar to that of moderate-intensity AE. https://www.chictr.org.cn/showproj.html?proj=178886, identifier ChiCTR2300074357.

Butyrate-promoting fibers improves fasting plasma glucose levels in subjects with prediabetes – A randomized, double-blinded, placebo-controlled crossover study

Butyrate-promoting fibers improves fasting plasma glucose levels in subjects with prediabetes – A randomized, double-blinded, placebo-controlled crossover study

Effectiveness and safety of the combination of sodium–glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies

BackgroundRandomized controlled trials and real-world studies suggest that combination therapy with sodium–glucose transport protein 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated with improvement in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), body mass index (BMI), and total cholesterol levels. However, a systematic review of available real-world evidence may facilitate clinical decision-making in the real-world scenario. This meta-analysis assessed the safety and effectiveness of combinations of SGLT2is + GLP-1RAs with a focus on their cardioprotective effects along with glucose-lowering ability in patients with type 2 diabetes mellitus (T2DM) in a real-world setting.MethodsElectronic searches were performed in the PubMed/MEDLINE, PROQuest, Scopus, CINAHL, and Google Scholar databases. Qualitative analyses and meta-analyses were performed using the Joanna Briggs Institute SUMARI software package and Review Manager v5.4, respectively.ResultsThe initial database search yielded 1445 articles; of these, 13 were included in this study. The analyses indicated that SGLT2is + GLP-1RAs combinations were associated with significantly lower all-cause mortality when compared with individual therapies (odds ratio [95% confidence interval [CI] 0.49 [0.41, 0.60]; p < 0.00001). Significant reductions in BMI (− 1.71 [− 2.74, − 0.67]; p = 0.001), SBP (− 6.35 [− 10.17, − 2.53]; p = 0.001), HbA1c levels (− 1.48 [− 1.75, − 1.21]; p < 0.00001), and FPG (− 2.27 [− 2.78, − 1.76]; p < 0.00001) were associated with the simultaneous administration of the combination. Changes in total cholesterol levels and differences between simultaneous and sequential combination therapies for this outcome were not significant.ConclusionThis systematic review and meta-analysis based on real-world data suggests that the combination of SGLT2is + GLP-1RAs is associated with lower all-cause mortality and favorable improvements in cardiovascular, renal, and glycemic measurements. The findings drive a call-to–action to incorporate this combination early and simultaneously in managing T2DM patients and achieve potential cardiovascular benefits and renal protection.Graphical

Improvement of periodontal parameters following intensive diabetes care and supragingival dental prophylaxis in patients with type 2 diabetes: A prospective cohort study.

This study aimed to investigate the effects of diabetes care on periodontal inflammation. This prospective cohort study included 51 Japanese patients with type 2 diabetes who underwent intensive diabetes care including educational hospitalization and regular outpatient treatment for 6 months. Dental prophylaxis without subgingival scaling was provided three times during the observational period. Associations between changes in periodontal parameters and glycaemic control levels were evaluated using multiple regression analysis. Overall, 33 participants (mean age: 58.7 ± 12.9) were followed up for 6 months. At baseline examination, 82% were diagnosed with Stage III or IV periodontitis. Haemoglobin A1c (HbA1c) level changed from 9.6 ± 1.8% at baseline to 7.4 ± 1.3% at 6 months. The ratio of probing pocket depth (PPD) ≥4 mm, bleeding on probing (BOP), full-mouth plaque control record (PCR), periodontal epithelial surface area (PESA) and periodontal inflamed surface area (PISA) also significantly improved. The reduction in PPD and PESA was significantly associated with changes in both HbA1c and fasting plasma glucose (FPG) levels, and the reduction in PISA was significantly associated with an improvement in FPG after adjusting for smoking, change in body mass index and full-mouth PCR. This is the first study to report a significant improvement in PPD and BOP after intensive diabetes care and dental prophylaxis without subgingival scaling. UMIN000040218.

Effect of Vortioxetine in Comparison to Fluoxetine on Metabolic Parameters in Patients With Depressive Disorder: A Randomized Controlled Trial.

Background Major depressive disorder (MDD) is a debilitating mood disorder that increases the risk of metabolic syndrome (MS), emphasizing the need for mental and physical health treatments. Although many studies have linked atypical antipsychotics to metabolic disturbances, there is limited evidence linking selective serotonin reuptake inhibitor use to MS. This study aimed to assess the risk of MS among patients with MDD who were administered vortioxetine and fluoxetine. Methodology This was a prospective, open-label, randomized controlled trial conducted in the psychiatry department. Using computer-generated random numbers, the physician assigned fluoxetine 20 mg or vortioxetine 10 mg and recorded MS parameters at baseline and each visit (4, 8, 12, 16, 20, and 24 weeks). This study was registered with CTRI (CTRI/2021/07/034892). Results A total of 122 participants were allocated randomly to the following two groups: group A (n = 60) and group B (n = 62). An independent-sample t-test showed a significant improvement in fasting plasma glucose (FPG) at week eight (p = 0.005), triglycerides (TGs) at week 16 (p = 0.005), high-density lipoprotein (HDL) at week 20 (p = 0.005), and waist circumference at week 24 (p = 0.005) in group A compared to group B.However, systolicblood pressure (SBP) and diastolic blood pressure (DBP) were not significantly associated with either group (p = 0.126 and p = 0.793, respectively). Overall depression remission (Hamilton Depression Rating Scale (HAM-D)) and medication adherence rating scale scores were similar between groups (p = 0.337 and 0.325, respectively). Furthermore, most adverse drug reactions were possibly associated with the study drugs. Conclusions In comparison to group B, group A showed significant improvements in FPG, HDL, and waist circumference more effectively; however, both groups led to higher TG levels, with non-significant numerical improvements observed in SBP and DBP in both groups. In addition, both treatment groups reduced the HAM-D score and had a similar MDD remission rate.

Effect of semaglutide on global longitudinal strain and global myocardial work efficiency in patients with uncontrolled type 2 diabetes mellitus and obesity

Abstract Background Type 2 Diabetes mellitus (T2DM) increases of two-to three-fold the risk of cardiovascular disease (CVD). Cardiovascular outcome trials (CVOTs) demonstrated that glucagon-like peptide 1-receptor agonists (GLP1-RAs), as semaglutide in SUSTAIN-6 study, have effectively reduced CV risk in T2DM patients, so their use is recommended by guidelines. Purpose The objective of our work was to evaluate the effect of Semaglutide administration in a cohort of uncontrolled diabetic patients (within 5 years from diagnosis) on oxidative stress validated markers (8-isoprostane and NOX-2), platelet activation indicators (Sp-Selectin) and subclinical myocardial damage evaluated by measurement of deformation and efficiency parameters, obtained by speckle tracking echocardiography (STE). Methods We enrolled 70 Caucasian patients (mean age 65.5±8.2) with T2DM and obesity, 54 men and 16 women, 85.7% with hypertension, 14.2% with chronic obstructive pulmonary disease, 57.1% with sleep apnea syndrome, 18.5% with chronic kidney disease, and 41.4% with dyslipidemia. All patients were treated with statins and metformin, 42.8% with insulin, 24.2% with diuretics, 37.1% with ACE inhibitors, and 48.5% with angiotensin receptor antagonists. In the study the mean dose of semaglutide was 0.59±0.29 mg/week, no serious adverse events were reported. Results After 6 months of follow-up a significant improvement in fasting plasma glucose, insulinemia, HOMA, IGF-1, HbA1c and BMI (p&amp;lt;0.0001) was reported. In addition, there was a significant reduction in biomarkers of oxidative stress such as 8-isoprostane, Nox-2 and uric acid (p&amp;lt;0.0001), biomarkers of platelet activity such as Sp-Selectin and high-sensitivity C-reactive protein (hs-CRP) (p&amp;lt;0.0001). Moreover, we observed a significant improvement in left ventricular myocardial deformation parameters such as Global longitudinal strain (GLS) (p&amp;lt;0.0001) and global myocardial work efficiency (GWE) (p&amp;lt;0.0001). The linear correlation analysis showed that variation (Δ) GLS was inversely correlated with ΔHOMA (p=0.011), Δuric acid (p=0.025) and ΔSp-selectin (p&amp;lt;0.0001); ΔGWE was inversely correlated with ΔHOMA (p=0.011), Δuric acid (p=0.025) and ΔSp-selectin (p&amp;lt;0.0001). From stepwise multivariate linear regression model, ΔSp-selectin, ΔHOMA and Δuric acid justifying 27.8%(p&amp;lt;0.0001), 5.6%(p=0.010) and 4.4%(p=0.023) of ΔGLS variation, respectively. Instead ΔNOX-2, Δhs-CRP and ΔBMI justifying 22.3%(p&amp;lt;0.0001), 15.6%(p&amp;lt;0.0001), and 4.0%(p=0.022) of ΔGWE variation, respectively. Conclusion Treatment for 6 months with Semaglutide, in patients with uncontrolled T2DM and obesity, improved GLS and GWE. It’s plausible that this improvement may be justified by the reduction of inflammatory, oxidative stress and platelet activation parameters together with favorable metabolic changes; thus promoting coronary microcirculation protection with positive effects on myocardial contractility.

Effects of two different angiotensin receptor blockers on blood glucose level and HbA1c in type-2 diabetes mellitus patients with hypertension

Diabetes mellitus is a common metabolic disorder characterized by chronic hyperglycemia and disturbance of carbohydrate, fats, and protein metabolism. Type 2 diabetes mellitus results from reduced insulin secretion, decreased glucose utilization, and increased glucose production, which results in hyperglycemia. Hypertension further increases the risk of cardiovascular diseases, including coronary heart disease (CHD), congestive heart failure (CHF), ischemic and hemorrhagic stroke, renal failure, and peripheral arterial disease (PAD). Angiotensin receptor blockers (ARBs) are very effective antihypertensive drugs. This study was done to find the effects of two different angiotensin receptor blockers on various biochemical markers in type-2 diabetes mellitus patients.MethodsThis was a prospective interventional study, comparing two ARBs Azilsartan and telmisartan, involving 76 patients with type 2 diabetes mellitus and hypertension.ResultsBoth drugs controlled blood pressure equally. The study showed that improvement in fasting plasma glucose was more with Azilsartan as compared to Telmisartan but their mean difference is not statistically significant (p > 0.05). The improvement in post-prandial plasma glucose and HbA1C was more with Telmisartan as compared to Azilsartan but only mean HbA1C was statistically significant (p < 0.05).ConclusionsTelmisartan has a better impact on HbA1c reduction than Azilsartan, as a part of the pleotropic effect of ARBs.

Salsalate: a pleotropic anti-inflammatory drug in the treatment of diabetes, obesity, and metabolic diseases.

Type two Diabetes Mellitus (T2DM) is a rising epidemic. Available therapeutic strategies have provided glycaemic control via HbA1c reduction but fail to provide clinically meaningful reduction in microvascular and macrovascular (cardiac, renal, ophthalmological, and neurological) complications. Inflammation is strongly linked to the pathogenesis of T2DM. Underlying inflammatory mechanisms include oxidative stress, endoplasmic reticulum stress amyloid deposition in the pancreas, lipotoxicity, and glucotoxicity. Molecular signalling mechanisms in chronic inflammation linked to obesity and diabetes include JANK, NF-kB, and AMPK pathways. These activated pathways lead to a production of various inflammatory cytokines, such as Interleukin (IL-6), tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP), which create a chronic low-grade inflammation and ultimately dysregulation of glucose homeostasis in the liver, skeletal muscle, and smooth muscle. Anti-inflammatory agents are being tested as anti-diabetic agents such as the IL-1b antagonist, Anakinra, the IL-1b inhibitor, Canakinuma, the IL-6 antagonists such as Tocilizumab, Rapamycin (Everolimus), and the IKK-beta kinase inhibitor, Salsalate. Salsalate is a century old safe anti-inflammatory drug used in the treatment of arthritis. Long-term safety and efficacy of Salsalate in the treatment of T2DM have been evaluated, which showed improved fasting plasma glucose and reduced HbA1C levels as well as reduced pro-inflammatory markers in T2DM patients. Current publication summarizes the literature review of pathophysiology of role of inflammation in T2DM and clinical efficacy and safety of Salsalate in the treatment of T2DM.

Effect of hydroxychloroquine on beta cell function, insulin resistance, and inflammatory markers in type 2 diabetes patients uncontrolled on glimepiride and metformin therapy.

Very few studies have assessed the impact of hydroxychloroquine (HCQ) on insulin resistance, beta cell function, and inflammatory markers in diabetics which takes paramount importance in understanding the mechanism of its anti-diabetic effect. To assess the effect of hydroxychloroquine on beta cell function and insulin resistance and inflammatory markers in type 2 diabetes patients uncontrolled on glimepiride and metformin combination. 30 T2DM patients were inadequately controlled on glimepiride and metformin combination with an HbA1c between 7.5 and 10% (both inclusive) and were given hydroxychloroquine 400mg in addition to glimepiride and metformin during the 12-week study period. Beta cell function, insulin resistance, high-sensitivity C-reactive protein (hsCRP), adiponectin, interleukin-6 (IL6), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and glycated hemoglobin (HbA1c) were assessed at baseline and at 12weeks after addition of 400mg hydroxychloroquine. With addition of HCQ, there was a significant improvement in both beta cell function and insulin resistance (p < 0.001). There was also significant improvement in FPG, PPG, and HbA1c along with significant improvement in IL6, hsCRP, and adiponectin levels post 12weeks of adjunctive treatment with hydroxychloroquine. The changes in beta cell function and insulin resistance correlated significantly with the changes in IL6, hsCRP, and adiponectin levels. Addition of hydroxychloroquine as an add-on drug in uncontrolled diabetes significantly improves the beta cell function and the insulin resistance, along with significant improvement in adiponectin, hsCRP levels, and IL6 levels.

High-Intensity Interval Training Versus Moderate-Intensity Continuous Training for Improving Physical Health in Elderly Women.

In elderly women, a lack of regular physical exercise may result in faster decreases in general health and functional performance. Although high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) have been effectively applied in young and clinical groups, there is no evidence to support their use in elderly women to achieve health benefits. Thus, the major goal of this study was to investigate how HIIT affected health-related outcomes in elderly women. Twenty-four inactive elderly women agreed to participate in the 16-week HIIT and MICT intervention. Body composition, insulin resistance, blood lipids, functional capacity, cardiorespiratory fitness, and quality of life were all measured before and after the intervention. The number of differences between groups was determined using Cohen's effect sizes, and the pre-post intra-group changes were compared using paired t-tests. Using 2 × 2 ANOVA, the time × group interaction effects between HIIT and MICT were evaluated. Body fat percentage, sagittal abdominal diameter, waist circumference, and hip circumference all were improved significantly in the 2 groups. HIIT substantially improved fasting plasma glucose and cardiorespiratory fitness as compared to the MICT. HIIT improved the lipid profile and functional ability more significantly compared to the MICT group. These findings show that HIIT is a useful exercise for improving elderly women's physical health.

Efficacy and Safety of Empagliflozin in Type 2 Diabetes Mellitus Saudi Patients as Add-On to Antidiabetic Therapy: A Prospective, Open-Label, Observational Study.

The Saudi Food and Drug Authority (SFDA) approved sodium-glucose cotransporter-2 (SGLT2) inhibitors in 2018. The efficacy and safety of empagliflozin (EMPA) have been confirmed in the U.S., Europe, and Japan for patients with type 2 diabetes mellitus (T2DM); however, analogous evidence is lacking for Saudi T2DM patients. Therefore, the current study aimed to assess the efficacy and safety of EMPA in Saudi patients (n = 256) with T2DM. This is a 12-week prospective, open-label, observational study. Adult Saudi patients with T2DM who had not been treated with EMPA before enrolment were eligible. The exclusion criteria included T2DM patients less than 18 years of age, adults with type one diabetes, pregnant women, paediatric population. The results related to efficacy included a significant decrease in haemoglobin A1c (HbA1c) (adjusted mean difference −0.93% [95% confidence interval (CI) −0.32, −1.54]), significant improvements in fasting plasma glucose (FPG) (−2.28 mmol/L [95% CI −2.81, −1.75]), and a reduction in body weight (−0.874 kg [95% CI −4.36, −6.10]) following the administration of 25 mg of EMPA once daily as an add-on to ongoing antidiabetic therapy after 12 weeks. The primary safety endpoints were the change in the mean blood pressure (BP) values, which indicated significantly reduced systolic and diastolic BP (−3.85 mmHg [95% CI −6.81, −0.88] and −0.06 mmHg [95% CI −0.81, −0.88], respectively) and pulse rate (−1.18 [95% CI −0.79, −3.15]). In addition, kidney function was improved, with a significant reduction in the urine albumin/creatinine ratio (UACR) (−1.76 mg/g [95% CI −1.07, −34.25]) and a significant increase in the estimated glomerular filtration rate (eGFR) (3.54 mL/min/1.73 m2 [95% CI 2.78, 9.87]). Furthermore, EMPA reduced aminotransferases (ALT) in a pattern (reduction in ALT > AST). The adjusted mean difference in the change in ALT was −2.36 U/L [95% CI −1.031, −3.69], while it was −1.26 U/L [95% CI −0.3811, −2.357] for AST and −1.98 U/L [95% CI −0.44, −3.49] for GGT. Moreover, in the EMPA group, serum high-density lipoprotein (HDL) significantly increased (0.29 mmol/L [95% CI 0.74, 0.15]), whereas a nonsignificant increase was seen in low-density lipoprotein (LDL) (0.01 mmol/L [95% CI 0.19, 0.18]) along with a significant reduction in plasma triglyceride (TG) levels (−0.43 mmol/L [95% CI −0.31, −1.17]). Empagliflozin once daily is an efficacious and tolerable strategy for treating Saudi patients with insufficiently controlled T2DM as an add-on to ongoing antidiabetic therapy.

Effect of High-Fat and Low-Fat Dairy Products on Cardiometabolic Risk Factors and Immune Function in a Low Birthweight Swine Model of Diet-Induced Insulin Resistance.

Although dairy intake has been shown to have a neutral or some beneficial effect on major cardiometabolic risk factors, the impact of dairy, and especially dairy fat, on immune function remains to be investigated. To understand the effect of consuming dairy fat on cardiometabolic risk factors and immune function, we used an established low birthweight (LBW) swine model of diet-induced insulin resistance to compare high-fat and low-fat dairy products to a control high-fat diet (CHF). LBW piglets were randomized to consume one of the 3 experimental HF diets: (1) CHF, (2) CHF diet supplemented with 3 servings/day of high-fat dairy (HFDairy) and (3) CHF diet supplemented with 3 servings/day of low-fat dairy (LFDairy). As comparison groups, normal birthweight (NBW) piglets were fed a CHF (NBW-CHF) or standard pig grower diet (NBW-Chow). A total of 35 pigs completed the study and were fed for a total of 7 weeks, including 1 week of CHF transition diet. At 12 weeks of age, piglets were euthanized. Fasting blood and tissue samples were collected. Ex vivo cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with pokeweed (PWM), phytohemagglutinin (PHA) and phorbol myristate acetate-ionomycin (PMA-I) were assessed. As expected, LBW-CHF piglets showed early signs of insulin resistance (HOMA-IR, P model = 0.08). Feeding high-fat dairy products improved fasting plasma glucose concentrations more than low-fat dairy compared to LBW-CHF (P < 0.05). Irrespective of fat content, dairy consumption had neutral effect on fasting lipid profile. We have also observed lower production of IL-2 after PWM and PHA stimulation as well as lower production of TNF-α and IFN-γ after PWM stimulation in LBW-CHF than in NBW-Chow (all, P < 0.05), suggesting impaired T cell and antigen presenting cell function. While feeding high-fat dairy had minimal effect on immune function, feeding low-fat dairy significantly improved the production of IL-2, TNF-α and IFN-γ after PWM stimulation, IL-2 and IFN-γ after PHA stimulation as well as TNF-α after PMA-I stimulation compared to LBW-CHF (all, P < 0.05). These data provide novel insights into the role of dairy consumption in counteracting some obesity-related cardiometabolic and immune perturbations.

Denosumab improves glucose parameters in patients with impaired glucose tolerance: a systematic review and meta-analysis

Objective Receptor activator of NF-κβ ligand (RANKL) is crucial for the development of hepatic insulin resistance and poor glucose uptake; therefore, inhibiting RANKL with Denosumab could improve fasting plasma glucose (FPG) and insulin (FPI). Methods A systematic review was conducted to evaluate the effects of Denosumab on glycemic parameters. PubMed, SCOPUS, EBSCO, and LILACS databases were searched for studies that investigated the effect of Denosumab on FPG, glycated hemoglobin (HbA1c), FPI, and Homeostatic Model Assessment for Insulin Resistance (HOMA1-IR). The pooled standard difference in means (SDM) and 95% confidence intervals (95%CI) were calculated. The results were stratified into (1) Normal Glucose Tolerance (NGT) and (2) Impaired Glucose Tolerance (IGT). Results Six publications (1203 participants) were included. There was a significant association between Denosumab and FPG (SDM = −0.388, 95%CI: −0.705 to −0.070, p = .017) and with HOMA1-IR (SDM = −0.223, 95%CI: −0.388 to −0.058, p = .008), but not for HbA1c and FPI. When stratified by glucose tolerance, the association between Denosumab and FPG, HbA1c, and HOMA1-IR was present for the IGT group. Lastly, Denosumab had a time-dependent effect on HbA1c (slope = −0.037, 95%CI: −0.059 to −0.015, p < .005). Conclusions Denosumab significantly improved glycemic parameters. This outcome was more prominent for subjects with compromised glucose tolerance, positing that Denosumab can be used as a treatment to improve glucose metabolism for persons with pre-diabetes and diabetes.

Culturally tailored lifestyle interventions for the prevention and management of type 2 diabetes in adults of Black African ancestry: a systematic review of tailoring methods and their effectiveness.

To evaluate the cultural tailoring methods used in type 2 diabetes (T2D), prevention and management interventions for populations of Black African ancestry and to examine their effectiveness on measures of glycaemia. Three databases were searched in October 2020; eligible studies used a randomised controlled trial (RCT) design to evaluate the effectiveness of culturally tailored lifestyle interventions compared with usual care for the prevention or management of T2D in adults of Black African ancestry. Cultural tailoring methods were evaluated using the Facilitator-Location-Language-Messaging (FiLLM) framework, whereby facilitator refers to delivery by individuals from the target community, language focuses on using native language or language appropriate to literacy levels, location refers to delivery in meaningful settings, and messaging is tailoring with relevant content and modes of delivery. Sixteen RCT were identified, all from USA. The mean age of participants was 55 years, majority female. Six of fifteen RCT reported significant improvements in glycated haemoglobin (HbA1c) at 6 and 8 months; one, in prediabetes, reported significantly improved fasting plasma glucose. Diabetes knowledge improvement (5/7 studies) was associated with HbA1c improvement. The majority tailored to location (12/16), facilitators (11/16), messaging (9/16) and language (6/16) domains of FiLLM. Those with ethnically matched facilitators and those which tailored to more than one domain showed the greatest HbA1C benefits. This evidence supports the effectiveness of culturally tailored lifestyle interventions for T2D management in populations of Black African ancestry, with further RCT needed to evaluate interventions for T2D prevention and for communities outside of the USA.

Decreased serum growth differentiation factor 15 levels after lifestyle intervention in patients with newly diagnosed type 2 diabetes mellitus

Recent studies noted that circulating growth differentiation factor 15 (GDF15) were closely related to metabolic states. Moreover, lifestyle intervention (LI) contributed to metabolic improvements among patients with diabetes. The study aimed to explore the changes of GDF15 levels and their influencing factors after 4 weeks of LI or LI combined with breakfast meal replacement (LI + MR) in newly diagnosed type 2 diabetes patients. A total of 84 patients with available serum samples at both baseline and Week-4 were enrolled in this biomarker substudy. All subjects underwent a 2-h 75 g oral glucose tolerance test at baseline and Week-4. Serum GDF15 levels were determined by a sandwich enzyme-linked immunosorbent assay. After 4 weeks of LI, GDF15 levels overall significantly decreased compared with baseline ( P < 0.05). ΔGDF15 levels were significantly and negatively associated with baseline GDF15 levels ( r = −0.450, P < 0.001). The optimal cut-off point of baseline GDF15 levels for predicting a GDF15 decrease after 4 weeks of LI was 904.57 pg/mL, with an area under curve of 0.699. Based on the cut-off point of 900 pg/mL, patients with baseline GDF15 ≥ 900 pg/mL had significantly decreased GDF15 levels after LI, while those <900 pg/mL had no significant changes. Regression models showed that baseline GDF15 level was an independent positive factor for the improvement of fasting plasma glucose and homeostasis model assessment for insulin resistance only in patients with baseline GDF15 levels ≥900 pg/mL. LI led to significantly decreased GDF15 levels among patients with newly diagnosed type 2 diabetes and its effect was more significant among patients with baseline GDF15 levels ≥900 pg/mL. • Growth differentiation factor 15 (GDF15) levels significantly decreased after 4 weeks of lifestyle intervention (LI). • The change of GDF15 levels between week-4 and baseline were negatively associated with the baseline GDF15 levels. • The effect of LI on the decrease of GDF15 levels was more significant among patients with baseline GDF15 levels ≥900 pg/ml.

Beneficial effects of liraglutide on peripheral blood vessels

Background/Aim. Macroangiopathy is the major cause of death and disability in type 2 diabetic patients. Studies have shown that liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, can protect cardiovascular system by inhibiting chronic inflammation of diabetes. However, a study about the effects of liraglutide on peripheral blood vessels and peripheral blood leukocytes has not been reported yet. The aim of this study was to determine vasculoprotective effect, vascular protection and mechanism of action of liraglutide in addition to its hypoglycemic effect. Methods. A total of 60 hospitalized patients with type 2 diabetes were recruited from December 2013 to December 2014 at the First Affiliated Hospital of Dalian Medical University, PR China. Before the treatment with liraglutide, height and weight were measured to calculate body mass index (BMI). Blood urea nitrogen (BUN) and so on were detected. Homeostasis model assessment of insulin resistance (HOMA-IR) and islet ? cell function (HOMA-?) were computed. After applying liraglutide for three months, all indexes were measured again. The effects of liraglutide on these indexes were analyzed by paired sample t-test. Results. After the treatment with liraglutide, values of glycosylated hemoglobin ? HbA1c (8.46 ? 1.62 vs. 7.26 ? 1.40%) and 2h postprandial blood glucose ? 2hPBG (11.95 vs. 9.6 mmol/L) decreased significantly (p &lt; 0.05). Body weight (87.3 vs. 82.5 kg) and BMI (30.37 vs. 28.63 kg/m2) decreased by 5.5% and 5.7%, respectively (p &lt; 0.05). Also, levels of triglycerides (TG) (2.57 ? 1.54 vs. 1.81 ? 0.70 mmol/L) and LDL-cholesterol (2.92 ? 0.78 vs. 1.89 ? 0.66 mmol/L) reduced significantly (p &lt; 0.05). Ankle-brachial index (ABI) decreased from 1.24 ? 0.10 to 1.14 ? 0.06 cm/s by 8%, while brachial-ankle pulse wave velocity (ba-PWV) decreased from 1,442.15 ? 196.26 to 1,316.85 ? 146.63 cm/s by 8.7%, and both differences were statistically significant (p &lt; 0.001). Conclusion. Liraglutide, with a good hypoglycemic effect, can significantly reduce postprandial blood glucose and HbA1c, but cannot significantly improve fasting plasma glucose, insulin resistance and islet ? cell function. It also considerably decreased body weight, BMI and TG. Liraglutide can significantly lower ba-PWV and ABI to protect peripheral blood vessels.

Effects of Nutritional Strategies on Glucose Homeostasis in Gestational Diabetes Mellitus: A Systematic Review and Network Meta-Analysis.

Background Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, and nutritional therapy is the basis of GDM treatment. However, the effects of different forms of nutritional supplementation on improving gestational diabetes are uncertain. Objective We conducted a network meta-analysis to evaluate the effects of supplementation with different nutrients on glucose metabolism in women with GDM. Methods We conducted a literature search using PubMed, EMBASE, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing the differences between different nutritional strategies in women with GDM. The Cochrane tool was used to assess the risk of bias. Pairwise meta-analysis and network meta-analysis were used to compare and rank the effects of nutritional strategies for the improvement of fasting plasma glucose (FPG), serum insulin, and homeostasis model assessment-insulin resistance (HOMA-IR). Results We included thirteen RCTs with a total of 754 participants. Compared with placebo, omega-3, magnesium, vitamin D, zinc, and probiotics were more beneficial for improving FPG, serum insulin, and HOMA-IR. Network analysis showed that vitamin D supplementation was superior to omega-3 (-3.64 mg/dL, 95% CI: -5.77 to -1.51), zinc (-5.71 mg/dL, 95% CI: -10.19 to -1.23), probiotics (-6.76 mg/dL, 95% CI: -10.02 to -3.50), and placebo (-12.13 mg/dL, 95% CI: -14.55 to -9.70) for improving FPG. Magnesium supplementation was more beneficial for decreasing serum insulin compared with probiotics (-5.10 μIU/mL, 95% CI: -9.32 to -0.88) and placebo (-7.80 μIU/mL, 95% CI: -9.32 to -0.88) and placebo (-7.80 Conclusion Vitamin D supplementation significantly reduced FPG and regulated HOMA-IR. Magnesium supplementation was superior in decreasing serum insulin than supplementation with other nutrients. Nutrient supplementation seemed to have an effect on glucose homeostasis maintenance in patients with GDM and may be considered an adjunctive therapy.

Efficacy of inulin supplementation in improving insulin control, HbA1c and HOMA-IR in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

Type 2 diabetes mellitus is a chronic disease that occurs among the general population. The insulin-lowering and homeostasis model assessment of insulin resistance-improving effects of inulin are unconfirmed. We conducted this meta-analysis to examine the efficiency and safety of inulin for improving insulin control, homeostasis model assessment of insulin resistance and HbA1c in patients with type 2 diabetes mellitus. We searched the Web of Science, PubMed, Embase and Cochrane Library databases for relevant articles published before June 1, 2019. In total, 225 randomized controlled trials regarding the efficiency of inulin for the treatment of type 2 diabetes mellitus compared to the efficacy of placebo or other treatments were examined. According to the inclusion and exclusion criteria, 9 trials with a total of 661 participants were included. We concluded that inulin supplementation can significantly improve fasting plasma glucose (SMD=-0.55, 95% CI -0.73 to -0.36, p=0), HOMA-IR (SMD=-0.81, 95% CI -1.59 to -0.03, p=0.042) and HbA1c (SMD=-0.69, 95% CI -0.92 to -0.46, p=0). Further subgroup analyses revealed a significant role of inulin supplementation for treatment durations ≥8 weeks (p= 0.038 for insulin, p=0.002 for HOMA-IR, p=0.032 for FPG, p=0 for HbA1c).