Reduced Fasting Plasma Glucose Research Articles

Diet and Pre-Intervention Washout Modifies the Effects of Probiotics on Gestational Diabetes Mellitus: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Dynamic interactions among gestational diabetes mellitus (GDM), gut microbiota, inflammation, oxidative stress, and probiotics are increasingly acknowledged. This meta-analysis aimed to summarize the effects of probiotics in GDM, focusing on lifestyle intervention and pre-intervention washout, in addition to metabolic, inflammation, oxidative stress, and pregnancy outcomes. Three electronic databases (i.e., PubMed, Scopus, and CENTRAL) were searched from inception until October 2020. A meta-analysis was performed, and the effect sizes were reported as either mean differences or odds ratios with 95% confidence intervals. Altogether, 10 randomized controlled trials enrolling 594 participants were included. The meta-analysis indicated that probiotics supplementation effectively reduced fasting plasma glucose by 3.10 mg/dL, and subgroup analyses suggested that the duration of intervention, number of species, pre-intervention washout period, and dietary intervention may determine the effects of probiotics. Probiotics also reduced the level of inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, and malondialdehyde), incidence of macrosomia, and newborn hospitalization. In conclusion, this meta-analysis suggests that probiotics may have positive effects on metabolic, inflammation, oxidative stress, and neonatal outcomes in women with GDM. Additionally, diet and pre-intervention washout may modify the effects of probiotics. Future studies are warranted on a larger scale to ascertain the clinical significance.

The Effect of Laparoscopic Sleeve Gastrectomy on Glycemic Control in Type 2 Diabetic Patients.

IntroductionThe prevalence of diabetes mellitus type II (T2DM) in Kuwait in 2013 was 23.09%, ranking ninth globally and second in the Middle East and North Africa (MENA) region. It’s been frequently reported as a growing public health concern. Our retrospective study will focus on the effect of laparoscopic sleeve gastrectomy (LSG) on the glycemic control of T2DM.MethodsFrom December 2012 to January 2014, 70 patients with T2DM underwent LSG during the study period. A retrospective patient file review was performed and a follow-up on participants was carried out in February 2014. Fasting plasma glucose (FPG) was taken pre- and post-operatively. Patients were followed up to monitor the change in diabetic medications in terms of quantity, type and dose.ResultsThe mean reduction of FPG after surgery was 2.94+3.66 (P < 0.001) over a mean interval of eight days (range, 0-34 days). Immediate reduction in FPG was seen in 61 patients (87%), and the greatest reduction was seen in the age group <40 years. Diabetes remission was seen in 49 patients (70%), while 20 (29%) had reduction in medication. All patients underwent a safe surgical procedure. There were no conversions to open surgery and no significant complications or mortalities.ConclusionsOur study shows that LSG procedure has an immediate positive effect on the glycemic control of T2DM, in addition to the long-term evidence of complete resolution of diabetes in most patients or improvement in glycemic control, which has further highlighted the positive outcome of LSG, diminishing morbidity, risk factors, co-morbidities and health-expenditure.

The effectiveness of Smartphone application-based education “Teman Diabetes” on clinical outcomes of Type-2 Diabetes mellitus patients

Introduction: Smartphone-based education has been proven to indirectly improve clinical outcomes of type-2 diabetes mellitus patients via practical disease management. “Teman Diabetes” is a new smartphone application that helps diabetics better manage their diabetes, and allows collaboration between diabetics, their inner circle, and medical professionals. However, there is still limited evidence about the effectiveness of “Teman Diabetes” on clinical outcomes of diabetic patients, especially type-2 diabetes mellitus. The objective of this research is to determine the positive effect of smartphone application-based education “Teman Diabetes” on the clinical outcomes of type-2 diabetes mellitus patients. The clinical outcomes measured were HbA1c and fasting plasma glucose levels. Method: Using a quasi-experimental design, a total of 83 participants were selected by consecutive sampling. Patients in the intervention group (n = 44) received "Teman Diabetes" when they assigned the informed consent form. Furthermore, they received a WhatsApp message containing a different link from the "Artikel" feature on the Teman Diabetes every week from the research team, from the second week to twelfth week. The control group (n = 39) only received standard therapy without any additional interventions. Patients in both groups were followed before and after 3 months (HbA1c and fasting plasma glucose levels). The statistical test used in this study is Mann-Whitney test for hypotheses and comparison of mean changes between groups; Wilcoxon test for comparison of mean changes between treatments; and analysis of covariance (ANCOVA) test for the effect of confounding variables. Results: After 3 months, the mean HbA1c reduction was greater in the intervention group by -0.7 ± 0.9% (P&lt;0.001) than in the control group by -0.1 ± 1.1% (P=0.17). Also, the mean fasting plasma glucose reduction was greater in the intervention group by -25.0 ± 71.4mg/dl (P=.02) instead of in the control group by 7.6 ± 72.4mg/dl (P=0.78). It is concluded that smartphone application-based education “Teman Diabetes” give a significant positive effect on clinical outcomes among type-2 diabetes mellitus patients. The main features that contributed to the clinical outcome of this study were "Artikel", "Forum", and "Edukasi" feature.

Metabolic Actions of a Supplement of Ilex Paraguariensis (An Extract of the Leaf Standardized to 2% I-Deoxinojirimcina), White Mulberry and Chromium Picolinate in Nondiabetic Subects with Dysglycemia: A Randomized Trial.

Aim: To prove if a nutraceutical containing Ilex paraguariensis (Ilex L. spp. Aquifoliales) (an extract of the leaf standardized to 2% I-deoxinojirimcina), white mulberry (Morus spp., Moraceae), and chromium picolinate can be effective in improving glycemic status in subject with dysglycemia. Methods: We randomized patients to consume placebo or the nutraceutical, self-administered once a day, one tablet at breakfast, for 3 months. Results: A reduction in fasting plasma glucose, postprandial glucose, and glycated hemoglobin was observed with the nutraceutical combination, both compared to baseline and placebo. Data suggested a decrease in the Homeostasis Model Assessment index with the nutraceutical, both compared to baseline and placebo. The M value, an index of insulin sensitivity, obtained after nutraceutical treatment was higher compared to baseline. We recorded a decrease in total cholesterol, low-density lipoprotein-cholesterol, and triglycerides with the nutraceutical combination compared to baseline and placebo. A decrease in high-sensitivity C-reactive protein was observed with the nutraceutical combination compared to baseline and placebo. Conclusions: A nutraceutical containing Ilex paraguariensis, white mulberry, and chromium picolinate can be helpful in improving glycemic status and lipid profile in dysglycemic subjects.

Effects of a novel polyphenol-rich plant extract on body composition, inflammation, insulin sensitivity, and glucose homeostasis in obese mice.

The worldwide prevalence of obesity, metabolic syndrome and type 2 diabetes (T2D) is reaching epidemic proportions that urge the development of new management strategies. Totum-63 is a novel, plant-based polyphenol-rich active principle that has been shown to reduce body weight, fasting glycemia, glucose intolerance, and fatty liver index in obese subjects with prediabetes. Here, we investigated the effects and underlying mechanism(s) of Totum-63 on metabolic homeostasis in insulin-resistant obese mice. Male C57Bl6/J mice were fed a high-fat diet for 12 weeks followed by supplementation with Totum-63 for 4 weeks. The effects on whole-body energy and metabolic homeostasis, as well as on tissue-specific inflammation and insulin sensitivity were assessed using a variety of immunometabolic phenotyping tools. Totum-63 decreased body weight and fat mass in obese mice, without affecting lean mass, food intake and locomotor activity, and increased fecal energy excretion and whole-body fatty acid oxidation. Totum-63 reduced fasting plasma glucose, insulin and leptin levels, and improved whole-body insulin sensitivity and peripheral glucose uptake. The expression of insulin receptor β and the insulin-induced phosphorylation of Akt/PKB were increased in liver, skeletal muscle, white adipose tissue (WAT) and brown adipose tissue (BAT). Hepatic steatosis was also decreased by Totum-63 and associated with a lower expression of genes involved in fatty acid uptake, de novo lipogenesis, inflammation, and fibrosis. Furthermore, a significant reduction in pro-inflammatory macrophages was also observed in epidydimal WAT. Finally, a potent decrease in BAT mass associated with enhanced tissue expression of thermogenic genes was found, suggesting BAT activation by Totum-63. Our results show that Totum-63 reduces inflammation and improves insulin sensitivity and glucose homeostasis in obese mice through pleiotropic effects on various metabolic organs. Altogether, plant-derived Totum-63 might constitute a promising novel nutritional supplement for alleviating metabolic dysfunctions in obese people with or without T2D.

107-LB: Relative Contribution of Fasting Plasma and Postprandial Glucose to HbA1c and TIR in People with T1D on Basal-Bolus Insulin Therapy

Background: A recent report was published on the contribution of fasting plasma glucose (FPG) and postprandial glucose (PPG) to HbA1c and time in range (%TIR) in people with type 2 diabetes on multiple daily injection regimens using prandial Humalog® (Lispro). We extended this analysis to type 1 diabetes (T1D) using data from people randomized to 26 weeks of mealtime ultra rapid lispro (URLi; N=451), postmeal URLi (N=329) or mealtime Humalog (N=442) in the phase 3 trial, PRONTO-T1D, and its continuous glucose monitoring (CGM) substudy. Methods: A multivariate regression model was used to quantify the contribution of FPG and PPG change to the change in HbA1c and %TIR. The contribution of PPG relative to FPG was determined. %TIR was derived from 10-point self-monitored blood glucose (SMBG) and CGM data from the CGM substudy. Only results for the mealtime groups are presented here. Results: With URLi treatment, a 1 mmol/L reduction in FPG and PPG was associated with a 0.11% ± standard error 0.02% and 0.09% ± 0.01% reduction in HbA1c, respectively, both p&amp;lt;0.0001, with a contribution of PPG relative to FPG of 82%. Similar results were obtained with Humalog: A 1 mmol/L reduction in FPG and PPG was associated with reduction in HbA1c of 0.12% ± 0.02% and 0.07% ± 0.02%, respectively, both p&amp;lt;0.0001, but the contribution of PPG relative to FPG was 58%. For SMBG-derived %TIR, with URLi treatment, a 1 mmol/L reduction in FPG and PPG was associated with an increase in %TIR of 10.0% ± 0.53% and 8.6% ± 0.47%, respectively, all p&amp;lt;0.0001. Similarly, with Humalog, a 1 mmol/L reduction in FPG and PPG was associated with an increase in %TIR of 9.8% ± 0.56% and 8.6% ± 0.52%, respectively, all p&amp;lt;0.0001 A similar trend was observed with CGM data, although the absolute values of contributions of FPG and PPG differed. Conclusions: Changes in FPG and PPG significantly impacted HbA1c and %TIR in people with T1D, reinforcing the need to manage both FPG and PPG to achieve optimal glycemic control. Disclosure C. Piras de oliveira: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. A. Dellva: Employee; Self; Eli Lilly and Company. J. M. Bue-valleskey: Employee; Self; Eli Lilly and Company. A. M. Chang: Employee; Self; Eli Lilly and Company. F. B. Chigutsa: None. B. Liao: Employee; Self; Eli Lilly and Company. Funding Eli Lilly and Company

Efficacy of green jackfruit flour as a medical nutrition therapy replacing rice or wheat in patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled study

Background/ObjectivesMedical nutrition therapy along with pharmacological interventions as a multidisciplinary approach is required to treat type 2 diabetes mellitus (T2DM). This study evaluated the efficacy of Jackfruit365™ green jackfruit flour as an integral part of daily meal in patients with T2DM.Subjects/MethodsThis was a randomized, double-blind, placebo-controlled study conducted between May 2019 and February 2020. Patients of either sex aged ≥18 to ≤60 years with a diagnosis of T2DM for >1 year receiving oral antihyperglycemic agents were randomized (1:1) to receive either jackfruit flour 30 g/day (Group A) or placebo flour (Group B) (breakfast and dinner) daily for 12 weeks replacing an equal volume of rice or wheat flour. The primary endpoint was a mean change in glycosylated hemoglobin (HbA1c). Other endpoints were mean changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), lipid profile, and body weight. The independent t-test was used to compare changes between the groups.ResultsA total of 40 patients were enrolled (n = 20 each). A significantly higher reduction in HbA1c was observed in Group A compared to Group B from baseline to week 12 [−2.73 mmol/mol (−0.25%) vs. 0.22 mmol/mol (0.02%), p = 0.006]. The mean change in FPG and PPG was significantly higher in Group A than that of Group B (p = 0.043 and p = 0.001). The continuous glucose monitoring showed decreasing mean blood glucose in 7 days of administration of jackfruit flour meal.ConclusionPatients from Group A had a significantly higher reduction in HbA1c, FPG, and PPG than Group B demonstrating the efficacy of jackfruit flour in glycemic control as medical nutrition therapy replacing an equal volume of rice or wheat flour in daily meal.Clinical trial registryCTRI/2019/05/019417.

Real-world evidence on the effectiveness and safety of gliclazide extended release treatment in Indian patients with type 2 diabetes undergoing Ramadan fast: an analysis from the global DIA-RAMADAN study

Background. Glycaemic imbalance, especially hypoglycaemia, is one of the greatest risks for patients with type 2 diabetes mellitus (T2DM) during Ramadan fasting. This paper outlines the efficacy and safety of gliclazide extended-release (XR) in Indian patients with T2DM enrolled in the global DIA-RAMADAN study. Methods. Adults (aged ≥ 18 years) with T2DM who chose to fast during Ramadan and received a gliclazidebased regimen once daily for 90 days before Ramadan were included in the study. Baseline and end-of-study visits were conducted 6–8 weeks before and 4–6 weeks after Ramadan, respectively. The primary outcome was the incidence of ≥ 1 symptomatic hypoglycaemic event (HE). Changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight were secondary outcomes. Results. Among 246 Indian patients enrolled in the study, most (78.9%, n = 194) were at moderate/low risk as per the International Diabetes Federation and Diabetes and Ramadan guidelines. Most patients (69.1%) received gliclazide XR as monotherapy, and the rest received gliclazide XR with metformin or other antidiabetic therapy. Significant reductions in HbA1c (−0.5 ± 0.8%, P &lt; 0.001) and FPG (−21.8 ± 59.4 mg/dL, P &lt; 0.001) levels were observed but the slight reduction in body weight was not statistically significant (−0.3 ± 3.7 kg, P = 0.614) in patients post-Ramadan. Overall, no HE was reported in Indian patients with T2DM during Ramadan fasting. Conclusion. Overall, the effectiveness and safety of gliclazide XR in Indian patients were consistent with that observed in the global cohort. Gliclazide XR significantly reduced HbA1c with no incidence of hypoglycaemic events in Indian patients with type 2 diabetes undergoing Ramadan fast, suggesting that gliclazide XR may be used without dose modification at Iftar to maintain optimal glycaemic control during Ramadan.

Saskatoon berry powder reduces hepatic steatosis and insulin resistance in high fat-high sucrose diet-induced obese mice

Non-alcoholic fatty liver disease is a common metabolic disorder associated with insulin resistance and lacks a specific treatment. Our previous studies demonstrated that freeze-dried Saskatoon berry powder (SBp) reduced high fat-high sucrose (HFHS) diet-induced hyperglycemia and insulin resistance in mice. The present study examined the effect of SBp and one of its active components, cyanidin-3-glucoside (C3G), on hepatic steatosis in mice fed with HFHS diet for 10 weeks. HFHS diet significantly increased fasting plasma glucose, cholesterol, triglycerides, insulin resistance, inflammatory markers (tumor necrosis factor-α, monocyte chemotactic protein-1, plasminogen activator inbitor-1), alanine aminotransferase activity, and monocyte adhesion compared to control diet. In the liver, HFHS diet increased steatosis, lipid accumulation, collagen deposition, and the abundance of patatin-like phospholipase domain-containing 3, CCAAT-enhancer-binding protein homologous protein, toll-like receptor-4, and macrophage marker. Supplementation with SBp (5%) or C3G in an amount corresponding to that in 5% SBp to HFHS diet had similar effects to reduced fasting plasma glucose, liver steatosis, enzyme activity, lipid, collagen and macrophage deposition, hyperglycemia, hyperlipidemia, insulin resistance, monocyte adhesion, markers related to liver steatosis, inflammation, oxidative or endoplasmic reticulum stress in the peripheral circulation and/or liver compared to mice fed with HFHS diet alone. No significant difference in the studied variables was detected between mice treated with HFHS+SBp and C3G diet. The results suggest that SBp or C3G administration attenuates HFHS diet-induced liver steatosis in addition to insulin resistance and chronic inflammation in mice. C3G may contribute to the beneficial effects of SBp.

Therapeutic effects of an aspalathin-rich green rooibos extract, pioglitazone and atorvastatin combination therapy in diabetic db/db mice.

Oral therapeutics used to treat type 2 diabetes and cardiovascular disease often fail to prevent the progression of disease and their comorbidities. Rooibos (Aspalathus linearis), an endemic South African plant used as an herbal tea, has demonstrated positive effects on glycemia and hypercholesterolemia. However, the treatment efficacy of rooibos extract in combination with conventional hypoglycemic and hypolipidemic medications on blood glucose and lipid profiles has not been established. This study aimed to investigate the effects of combining an aspalathin-rich green rooibos extract (Afriplex GRT™) with pioglitazone and atorvastatin, on blood glucose and lipid levels in obese diabetic (db/db) mice. Six-week-old male db/db mice and their nondiabetic lean littermate controls (db+) were divided into 8 experimental groups (n = 6/group). Db/db mice were treated daily either with pioglitazone (25 mg/kg), atorvastatin (80 mg/kg) and GRT (100 mg/kg), a combination of either drug with GRT or a combination of GRT-pioglitazone and atorvastatin for 5 weeks. Untreated vehicle controls were given dimethyl sulfoxide (0.1%) and phosphate buffered saline solution. At termination, serum and liver tissue were collected for lipid and gene expression analysis. Treatment with GRT, pioglitazone and atorvastatin combination effectively lowered fasting plasma glucose (FPG) levels in db/db mice (p = 0.02), whilst increasing body weight, liver weight, and reducing retroperitoneal fat weight. Atorvastatin monotherapy was effective at reducing cholesterol (from 4.00 ± 0.12 to 2.93 ± 0.13, p = 0.0003), LDL-C (from 0.58 ± 0.04 to 0.50 ± 0.00, p = 0.04), HDL-C (from 2.86 ± 0.05 to 2.50 ± 0.04, p = 0.0003) and TG (from 2.77 ± 0.50 to 1.48 ± 0.23, p = 0.04), compared to the untreated diabetic control. The hypotriglyceridemic effect of atorvastatin was enhanced when used in combination with both GRT and pioglitazone. The addition of pioglitazone to GRT significantly lowered FPG and TG. In db/db mice, Apoa1 was significantly downregulated in the liver, whilst Pparγ was significantly upregulated compared to their db+ counterparts. GRT monotherapy downregulated Apoa1 expression (p = 0.02). Atorvastatin combined with GRT significantly downregulated mRNA expression of Apoa1 (p = 0.03), whilst upregulating the expression of Pparγ (p = 0.03), Pparα (p = 0.002), Srebp1 (p = 0.002), and Fasn (p = 0.04). The GRT-pioglitazone-atorvastatin combination therapy downregulated Apoa1 (p = 0.006), whilst upregulating Fasn (p = 0.005), Pparα (p = 0.041), and Srebp1 (p = 0.03). Natural products can improve the efficacy of current drugs to prevent diabetes-associated complications. GRT in combination with pioglitazone enhanced the reduction of FPG, whilst the addition of atorvastatin to the combination, significantly lowered triglyceride levels. However, when GRT was used in combination with atorvastatin only cholesterol levels were affected. Although these results confirm both glucose- and lipoprotein-lowering biological effects of GRT in combination with pioglitazone and atorvastatin, increased expression of genes involved in lipogenesis, cholesterol, and fatty acid transport, β-oxidation, and synthesis and storage of fatty acids, may exacerbate the hepatotoxic effects of atorvastatin.

Switching to iGlarLixi versus continuation of a daily or weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) in insufficiently controlled type 2 diabetes: A LixiLan-G trial subgroup analysis by HbA1c and GLP-1 RA use at screening.

AimIn people with type 2 diabetes (T2D) requiring intensification beyond glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and oral antihyperglycaemic drugs (OADs), switching to iGlarLixi was shown to be efficacious and well‐tolerated in the LixiLan‐G trial. This exploratory analysis of LixiLan‐G assessed the efficacy and safety of switching to iGlarLixi versus continuing GLP‐1 RA therapy, stratified by screening HbA1c level (≥7.0 to ≤7.5 %; >7.5 to ≤8.0 %; >8.0 to ≤9.0 % [≥53 to ≤58 mmol/mol; >58 to ≤64 mmol/mol; >64 to ≤75 mmol/mol]) and previous GLP‐1 RA regimen at screening (once/twice daily or once weekly).Materials and MethodsEndpoints for all subgroups included: change in HbA1c, achievement of HbA1c <7 % and hypoglycaemia events. Adverse events and changes in fasting plasma glucose (FPG), 2‐hour postprandial plasma glucose (PPG), 2‐hour PPG excursion and weight were analysed according to previous GLP‐1 RA regimen.ResultsSwitching to iGlarLixi in all subgroups resulted in significantly greater reductions in HbA1c and proportions of participants reaching HbA1c <7 % (including with no documented hypoglycaemia) at Week 26 compared with continued GLP‐1 RA treatment. Switching to iGlarLixi also led to significantly greater reductions in FPG, 2‐hour PPG, and 2‐hour PPG excursion, irrespective of previous GLP‐1 RA regimen. Rates of hypoglycaemia were low, but slightly higher in those who switched to iGlarLixi for all subgroups. Modest weight gain was seen with iGlarLixi, irrespective of previous GLP‐1 RA regimen.ConclusionsSwitching to iGlarLixi improved glycaemic control, regardless of screening HbA1c or previous GLP‐1 RA type, offering a simple, efficacious and well‐tolerated treatment intensification option for people with T2D inadequately controlled by GLP‐1 RAs and OADs.

Dietary Fibre Intake in Type 2 and New-Onset Prediabetes/Diabetes after Acute Pancreatitis: A Nested Cross-Sectional Study.

The association between intake of dietary fibre and glucose metabolism has been extensively investigated in numerous metabolic disorders. However, little is known about this association in individuals after an attack of acute pancreatitis (AP). The aim was to investigate the associations between intake of dietary fibre and markers of glucose metabolism in individuals with new-onset prediabetes or diabetes after acute pancreatitis (NODAP), pre-exiting type 2 prediabetes or diabetes, and normoglycaemia after acute pancreatitis. This cross-sectional study was nested within the parent prospective longitudinal cohort study. The studied markers of glucose metabolism were fasting plasma glucose and glycated haemoglobin. Habitual intake of dietary fibre was determined using the EPIC-Norfolk food frequency questionnaire. Multivariable linear regression analyses were conducted. The study included a total of 108 individuals after AP. In the NODAP group, increased intakes of total fibre (β = −0.154, p = 0.006), insoluble fibre (β = −0.133, p = 0.01), and soluble fibre (β = −0.13, p = 0.02) were significantly associated with a reduction in fasting plasma glucose. Increased intakes of vegetables (β = −0.069, p = 0.004) and nuts (β = −0.039, p = 0.038) were significantly associated with a reduction in fasting plasma glucose. Increased intake of nuts (β = −0.054, p = 0.001) was also significantly associated with a reduction in glycated haemoglobin. None of the above associations were significant in the other study groups. Habitual intake of dietary fibre was inversely associated with fasting plasma glucose in individuals with NODAP. Individuals after an attack of AP may benefit from increasing their intake of dietary fibre (specifically, vegetables and nuts) with a view to preventing NODAP.

Fasting and postprandial plasma glucose contribution to glycated haemoglobin and time in range in people with type 2 diabetes on basal and bolus insulin therapy: Results from a pooled analysis of insulin lispro clinical trials

AimsTo investigate the interrelations between glycaemic metrics of fasting plasma glucose (FPG), postprandial glucose (PPG), glycated haemoglobin (HbA1c), and percentage of time in target range 3.9 to 10.0 mmol/L (%TIR) in patients on insulin therapy.Materials and methodsA pooled analysis was conducted using datasets extracted from an integrated database of insulin lispro clinical trials (Eli Lilly and Company). Studies in patients with type 2 diabetes on basal‐bolus or basal‐plus insulin therapy, and with ≥7‐point self‐monitored blood glucose profiles were included in the analysis. A multivariate regression model was used to quantify the contribution of FPG and PPG change to the change in HbA1c and %TIR. In addition, a linear regression model was used to describe the relationship between %TIR and HbA1c.ResultsFive studies encompassing 1572 patients met the criteria for inclusion. On average, a 1‐mmol/L change in FPG was associated with 2.7 mmol/mol (0.25%) change in HbA1c (range 2.0 to 2.8 mmol/mol [0.18%–0.26%]; all P <0.0001), and a 1‐mmol/L change in PPG with 1.8 mmol/mol (0.16%) change in HbA1c (range 1.2 to 2.1 mmol/mol [0.11%–0.19%]; all P <0.01). Furthermore, a 1‐mmol/L reduction in FPG and PPG was associated with an increase in TIR of 6.5% (range 5.8%–9.2%) and 5.3% (range 4.1%–8.7%), respectively, all P <0.0001. A decrease in HbA1c of 10.9 mmol/mol (1%) corresponded with an increase in TIR of 8.3%, on average.ConclusionsIn patients with type 2 diabetes on basal‐bolus or basal‐plus insulin therapy, management of both FPG and PPG is important for achievement of HbA1c and TIR goals.

Clinical efficacy on glycemic control and safety of mesenchymal stem cells in patients with diabetes mellitus: Systematic review and meta-analysis of RCT data.

BackgroundDiabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs).Methods and findingsThe aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to provide a reliable numerical summary and the most comprehensive assessment of therapeutic efficacy and safety with MSCs in diabetes. PubMed, Web of Science, Ovid, the Cochrane Library and CNKI were searched. The retrieval time was from establishment of these databases to January 4, 2020. Seven RCTs were eligible for analysis, including 413 participants. Meta-analysis results showed that there were no significant differences in the reduction of fasting plasma glucose (FPG) compared to the baseline [mean difference (MD) = -1.05, 95% confidence interval (CI) (-2.26,0.16), P<0.01, I2 = 94%] and the control group [MD = -0.62, 95%CI (-1.46,0.23), P<0.01, I2 = 87%]. The MSCs treatment group showed a significant decrease in hemoglobin (Hb) A1c [random-effects, MD = -1.32, 95%CI (-2.06, -0.57), P<0.01, I2 = 90%] after treatment. Additionally, HbA1c reduced more significantly in MSC treatment group than in control group [random-effects, MD = -0.87, 95%CI (-1.53, -0.22), P<0.01, I2 = 82%] at the end of follow-up. However, as for fasting C-peptide levels, the estimated pooled MD showed that there was no significant increase [MD = -0.07, 95%CI (-0.30, 0.16), P<0.01, I2 = 94%] in MSCs treatment group compared with that in control group. Notably, there was no significant difference in the incidence of adverse events between MSCs treatment group and control group [relative risk (RR) = 0.98, 95%CI (0.72, 1.32), P = 0.02, I2 = 70%]. The most commonly observed adverse reaction in the MSC treatment group was hypoglycemia (29.95%).ConclusionsThis meta-analysis revealed MSCs therapy may be an effective and safe intervention in subjects with diabetes. However, due to the limited studies, a number of high-quality as well as large-scale RCTs should be performed to confirm these conclusions.

Role of zonulin and GLP-1/DPP-IV in alleviation of diabetes mellitus by peptide/polypeptide fraction of Aloe vera in streptozotocin- induced diabetic wistar rats

Ethno-pharmacological relevanceThe genus Aloe has a long history of usage in medicine. Aloe barbadensis Miller, commonly known as Aloe vera, is said to possess anti-diabetic, anti-inflammatory, anti-cancer, anti-microbial, immunomodulation, wound healing properties. Aim of the studyIn diabetes mellitus, loss in intestinal permeability is observed with high levels of zonulin and low levels of glucagon-like peptide-1 (GLP-1) leading to hyperglycemia. The aim of the study was to understand the role of peptide/polypeptide fraction (PPF) of Aloe vera in the alleviation of diabetes through maintaining the intestinal permeability by regulating the zonulin and GLP-1 levels. Materials and methodsThe PPF of Aloe vera was obtained through trichloroacetic acid precipitation. The anti-diabetic potential of the PPF was tested through DPP-IV inhibition, glucose diffusion assay, and by using Rin-m5F cells. The anti-diabetic potential of the PPF was tested at a dose of 0.450 mg/kg bw in vivo using streptozotocin-induced diabetic Wistar rats. The effect of PPF on fasting plasma glucose, insulin, glucagon, Zonulin, GLP-1, DPP-IV, levels were studied in diabetic rats. The histopathological studies of the pancreas, small intestine, and liver were carried out for organ-specific effects. ResultsPPF has the ability to reduce fasting plasma glucose levels with concomitant increase in insulin levels in streptozotocin-induced diabetic rats. It was also observed that increase in GLP-1 levels with a decrease in DPP-IV and zonulin levels thereby mitigating the loss of intestinal permeability. These findings correlate with the small intestine's histopathological observation where the excessive proliferation of epithelium in the small intestine of diabetic rats was reduced after PPF treatment. ConclusionThese results suggest that the PPF of Aloe vera alleviates diabetes through islet cell rejuvenation via GLP-1/DPP-IV pathway and thereby suggesting the usage of PPF as an alternate medicine for diabetes mellitus with the possibility to reduce the intestinal permeability and zonulin levels.

Efficacy and safety of Shenqi Jiangtang Granules plus oral hypoglycemic agent in patients with type 2 diabetes mellitus: A protocol for systematic review and meta-analysis of 15 RCTs.

Objective:Shenqi Jiangtang Granules (SQJTG) has been widely used to treat patients with type 2 diabetes mellitus (T2DM). But whether there exists sufficient evidence on the efficacy of SQJTG in the treatment of T2DM is unclear. In order to assess the effects of SQJTG for T2DM, a systematic review and meta-analysis of randomized controlled trials (RCTs) were carried out.Methods:Eight databases, namely, PubMed, The Cochrane Library, EMBASE, Web of Science, Chinese National Knowledge Infrastructure, Chinese Scientific Journals Full-Text Database, CBM, and Wanfang database were searched up to May 2020. According to the Cochrane standards, the selection of study, the extraction of data, the assessment of study quality, and the analyses of data were carried out strictly. Then a fixed or random effects model was applied to analyze the outcomes.Results:Fifteen studies (N = 1392) in total conformed the inclusion criteria to this meta-analysis. Two subgroups were identified, based on different dose of SQJTG: oral hypoglycemic agent (OHA) vs OHA plus SQJTG (1 g); OHA vs. OHA plus SQJTG (1.5–3 g). The pooled results showed that, in comparison with OHA, OHA plus SQJTG significantly reduced fasting plasma glucose in both 1 g subgroup and 1.5–3 g subgroup; 2-hour post-meal blood glucose was also greatly reduced in the SQJTG 1 g subgroup and the SQJTG 1.5–3 g subgroup. Compared with OHA, SQJTG 1 g subgroup significantly reduced levels of glycated hemoglobin A1c, as well as the SQJTG 1.5–3 g subgroup. Homeostasis model-insulin resistance index was also reduced in both SQJTG 1 g subgroup and SQJTG 1.5–3 g subgroup; SQJTG group can also significantly reduce the total adverse events especially in reducing the incidence of hypoglycemia.Conclusions:SQJTG is an effective and safe complementary treatment for T2DM patients. This meta-analysis provides an evidence for the treatment in patients with T2DM. While owing to the high heterogeneity and the trials’ small sample size, it's crucial to perform large-scale and strict designed studies.

Dates fruits effects on blood glucose among patients with diabetes mellitus: A review and meta-analysis.

Background & Objective:Dates fruit is known for its great nutritional value and two to three servings of dates fruit/day are beneficial for patients with diabetes. However, some may advice against this cheap and widely available fruit consumption. Besides, 12% of the population Worldwide are either suffering or are at risk of developing diabetes, but no previous meta-analysis has assessed this important issue. Thus, the study aimed to investigate the effects of date’s fruit on glycemia among patients with diabetes.Methods:A systematic literature search was conducted in PubMed, Medline, EBSCO, Cochrane, and Google Scholar databases for trials published in English from the first published article up to December 2020. The following keywords were used: “dates fruit and glycemic control”, “dates fruit and blood glucose”, “dates fruit and HbA1c” without limitations regarding the date of publication.Results:Out of the 942 references identified, only 10 cohorts from five full texts were included, a reduction of Fasting plasma glucose (FPG), odd ratio, -24.79, 95% CI=-34.75, -14.83 P =0.002. I2 for heterogeneity=79%, P <0.00001 and postprandial plasma glucose (PPPG), odd ratio -28.19, 95% CI=-60.66-4.29, P =<0.0001. I2 for heterogeneity=92%, P=0.09) was observed. While the effect on HbA1c was neutral, odd ratio, -.20, 95% CI=-.46 -.06, P=0.13. I2 for heterogeneity=0. %, P=0.55.Conclusion:Dates fruit was beneficial regarding glycemic control among patients with diabetes, physician may not need to restrict its use among patients with diabetes. The small number of the included studies and the heterogeneity observed in PPPG and FPG sub-analysis limited the current results. Further trials assessing the glycemic indices of various types of dates fruit are needed.

Berberine and Metformin in the Treatment of Type 2 Diabetes Mellitus: A Systemic Review and Meta-Analysis of Randomized Clinical Trials

Objective: To assess the effects of berberine and metformin on glucose in patients with type 2 diabets mellitus (T2DM) with a systematic review and meta-analysis. Methods: The databases including PubMed, Excerpta Medica Database (EMBase), Cochrane Library, Chinese National Knowledge Infrastructure database (CNKI), WanFang, the Chinese Scientific and Technical Journals database (VIP), China Doctor Dissertation Full-text Database (CDFD) and China Master Dissertation Full-text Database (CMFD) from the inception to April 2021 in Chinese or English language were searched. Randomized controlled trials (RCTs) of berberine only or combined with metformin versus metformin were included. Data extraction and paper quality assessment were conducted according to the Cochrane Handbook. RevMan 5.4 was used for the meta-analysis. Results: A total of thirteen studies were included, covering 1173 participants. The clinical heterogeneity of the included trials was relatively high. The methodological quality of most trials was generally low with bias in terms of random sequence generation, allocation concealment, blinding method, outcome data and selective reporting. Interventions were divided into two subgroups for analysis. Meta-analysis suggested that there was no statistical significance in the hypoglycemic effect between berberine and metformin for T2DM. However, berberine combined with metformin could reduce fasting plasma glucose (FPG) [MD = −1.49, 95% CI (−2.22, −0.76), P MD = −1.89, 95% CI (−2.94, −0.84), P = 0.0004], glycosylated hemoglobin A1c (HbA1c) [MD = −0.65, 95% CI (−0.91, −0.40), P MD = −0.53, 95% CI (−1.03, −0.03), P = 0.04] levels significantly compared with metformin group. No severe adverse effects were reported in all trials. Conclusions: The hypoglycemic effect of berberine alone is not better than metformin. But berberine combined with metformin has good efficacy and safety in the treatment of T2DM. The current clinical studies are low in methodology and reporting quality, which needs to be further proved by more high quality, large sample size and multi-center RCTs.

Liraglutide and Dulaglutide Have Comparable HbA1c Reduction in Emirati Patients with T2DM

Glucagon like peptide-1 is responsible for the incretin effect after a meal or an oral glucose load. Patients with type 2 diabetes mellitus have impairment of secretion and action of glucagon like peptide-1. This impairment can be overcome through pharmacological doses of glucagon like peptide-1 analogues. Aim of the Study: This study aimed at evaluation of the effect of treatment with glucagon like peptide-1 analogues; liraglutide and dulaglutide, in Emirati patients with type 2 diabetes mellitus. Glycemic control was the primary end point while the secondary end point was the effect on body mass index, blood pressure, heart rate, serum creatinine, lipid profile and estimated glomerular filtration rate. Patients & Methods: This is a retrospective study including 54 patients with type 2 diabetes mellitus. Patients used Liraglutide or Dulaglutide as add on therapy to oral antidiabetic medications for one year. Thirty-four patients used liraglutide 1.8 mg once daily and 20 patients used dulaglutide 1.5 mg once weekly. All patients were older than 18 years and had estimated glomerular filtration rate (>90 ml/min/1.73 m2). Body mass index, sitting blood pressure and heart rate were collected. Fasting plasma glucose, HbA1c, lipid panel and other biochemical parameters were also collected. Data were analysed before and at 6 and 12 months of glucagon like peptide-1 analogue treatment. Results: At 12 months of treatment, liraglutide significantly reduced fasting plasma glucose (11.3 ± 4 vs 7 ± 1.7, p

Mechanisms by which adiponectin reverses high fat diet-induced insulin resistance in mice

Adiponectin has emerged as a potential therapy for type 2 diabetes mellitus, but the molecular mechanism by which adiponectin reverses insulin resistance remains unclear. Two weeks of globular adiponectin (gAcrp30) treatment reduced fasting plasma glucose, triglyceride (TAG), and insulin concentrations and reversed whole-body insulin resistance, which could be attributed to both improved insulin-mediated suppression of endogenous glucose production and increased insulin-stimulated glucose uptake in muscle and adipose tissues. These improvements in liver and muscle sensitivity were associated with ∼50% reductions in liver and muscle TAG and plasma membrane (PM)-associated diacylglycerol (DAG) content and occurred independent of reductions in total ceramide content. Reductions of PM DAG content in liver and skeletal muscle were associated with reduced PKCε translocation in liver and reduced PKCθ and PKCε translocation in skeletal muscle resulting in increased insulin-stimulated insulin receptor tyrosine1162 phosphorylation, IRS-1/IRS-2-associated PI3-kinase activity, and Akt-serine phosphorylation. Both gAcrp30 and full-length adiponectin (Acrp30) treatment increased eNOS/AMPK activation in muscle and muscle fatty acid oxidation. gAcrp30 and Acrp30 infusions also increased TAG uptake in epididymal white adipose tissue (eWAT), which could be attributed to increased lipoprotein lipase (LPL) activity. These data suggest that adiponectin and adiponectin-related molecules reverse lipid-induced liver and muscle insulin resistance by reducing ectopic lipid storage in these organs, resulting in decreased plasma membrane sn-1,2-DAG-induced nPKC activity and increased insulin signaling. Adiponectin mediates these effects by both promoting the storage of TAG in eWAT likely through stimulation of LPL as well as by stimulation of AMPK in muscle resulting in increased muscle fat oxidation.