Decreased Fasting Plasma Glucose Research Articles

Comparative efficacy and safety of probiotics, prebiotics, and synbiotics for type 2 diabetes management: A systematic review and network meta-analysis

AimsTo compare the effects of probiotics, prebiotics, and synbiotics for type 2 diabetes (T2D) management. MethodsWe searched PubMed, Scopus, CENTRAL, and grey literature sources to December 2022 for randomized trials of the impacts of probiotics, prebiotics, or synbiotics in patients with T2D. We performed network meta-analyses with a Bayesian framework to calculate mean difference [MD] and 95 % credible interval [CrI] and rated the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results68 randomised trials were included. All results are presented in comparison to the placebo. Supplementation with probiotics (MD: -0.25 %, 95%CrI: -0.42, -0.08; GRADE = moderate) and synbiotics (MD: -0.31 %, 95%CrI: -0.61, -0.04; GRADE = very low) resulted in a trivial/unimportant decrease in glycated hemoglobin. Supplementation with probiotics (MD: -0.69 mmol/L, 95%CrI: -0.98, -0.40; GRADE = very low) and synbiotics (MD: -0.82 mmol/L, 95%CrI: -1.22, -0.43; GRADE = very low) resulted in a trivial/unimportant decrease in fasting plasma glucose. Supplementation with probiotics resulted in a small but important decrease in low-density lipoprotein cholesterol (MD: -0.19 mmol/L; 95%CrI: -0.34, -0.05; GRADE = very low). Supplementations had moderate effects on serum triglyceride (GRADE = low). ConclusionsExisting evidence is uncertain and does not support supplementation with probiotics, prebiotics, and synbiotics for T2D management.

Glycemic control and adverse effects in patients with type 2 diabetes receiving basal-bolus insulin regimen versus premixed insulin regimen: An observational study

Objectives: Several studies have compared the basal-bolus (BB) and premixed (PM) insulin regimens with varying results. This study aimed to evaluate the glycemic control and occurrence of hypoglycemia with these regimens in insulin-naïve patients with type 2 diabetes mellitus (T2D) in the Indian subpopulation. Materials and Methods: This was a 12-week (wk) prospective, observational study in 60 adult patients (distributed 1:1) with >7 years of T2D and uncontrolled with three oral drugs. Changes in glycemic parameters at wk4 and wk12 were assessed, and hypoglycemia events were also recorded. Results: The PM insulin showed a significant decrease in fasting plasma glucose (FPG) at wk4 from baseline (P = 0.02) and at wk12 (P < 0.001), while in the BB insulin group, the change was significant only at wk12 (P < 0.0001). There were greater reductions in the PM group in FPG at wk4 (PM vs. BB: P = 0.04) and wk12 (P = 0.03) compared to the BB group. The post-prandial plasma glucose in both groups significantly reduced from baseline at wk4 (PM group P = 0.034; BB group; P = 0.034) and wk12 (PM group P < 0.0001 and BB group: P < 0.0001). However, there were no between-group differences at wk4 (P = 0.12) but only at wk12 (P = 0.009) with greater reductions in the PM group. The PM group showed a slightly greater reduction in glycated hemoglobin versus the BB group (9.18% vs. 7.08%; P = 0.39). There was no significant difference (P = 0.49) in the incidence of hypoglycemia. Conclusion: Both treatments significantly improved glycemic control and were not associated with any severe episodes of hypoglycemia. Therefore, the choice should instead be guided by the insulin-related (posology, complexity) and patient-related (dietary habits, adherence levels) factors.

A Randomized, Double-Blind, Parallel-Group PhaseIII Trial Investigating the Glycemic Efficacy and Safety Profile of Fixed-Dose Combination Dapagliflozin and Linagliptin Over Linagliptin Monotherapy in Patients with Inadequately Controlled Type2 Diabetes with Metformin.

The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of dapagliflozin (10mg) and linagliptin (5mg) in comparison to linagliptin 5mg (Trajenta) in patients with insufficiently controlled type2 diabetes mellitus (T2DM) on metformin monotherapy. The double-blind, randomized, multicentric, parallel-group phaseIII trial screened 287 adult patients with T2DM (age 18-65years) from 16 sites across India. The recruited subjects were undergoing metformin monotherapy ≥ 1000mg/day for at least 28days. Patients with HbA1c of 7.5-10.5% (58-91mmol/l) (n = 232) after 2weeks of run-in period with linagliptin monotherapy and placebo dapagliflozin/linagliptin on metformin monotherapy were randomized (1:1) in parallel to once daily dapagliflozin/linagliptin 10/5mg or linagliptin 5mg for 16weeks. Patients were stratified on the basis of HbA1c (≤ 9.0% and > 9.0%; ≤ 75mmol/l and > 75mmol/l)). A total of 225 subjects completed 16weeks of treatment, 115 patients in the test group and 110 patients in the reference group. Dapagliflozin/linagliptin (p = 0.0003) exhibited a greater change in HbA1c from baseline than linagliptin (p < 0.0001) in 16weeks (mean reduction, - 1.28% vs - 0.83%). Test group showed a significant decrease in fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and body weight compared to the reference group. The FDC was well tolerated with adverse events being more frequent in the reference group. No serious adverse events (SAEs) were reported in the study. Dapagliflozin/linagliptin combination is a novel dipeptidyl peptidase4 (DPP4)/sodium-glucose co-transporter2 (SGLT2) inhibitor FDC approved in India for patients with T2DM. Potential limitations of this study are a small dose of dapagliflozin (10mg) in the FDC, a short study duration (30weeks) and a high minimum threshold for HbA1c (≤ 7.5%; ≤ 53mmol/l). Results indicate the FDC to be a superior therapeutic option over linagliptin for patients with T2DM on metformin monotherapy. CTRI/2022/08/044563; 01/08/2022.

The Effects of 12-Week Traditional Thai Exercise (Ruesi Dadton) on Glycemic Control and Inflammatory Markers in Prediabetes: A Randomized Controlled Trial.

Hyperglycemia and inflammation are hallmarks of the prediabetes stage, which has the potential to develop into diabetes mellitus. In this stage, lifestyle changes and exercise are recommended and have been shown to be effective. However, there has been insufficient study investigating the impact of Ruesi Dadton (RD) exercise on prediabetes. Therefore, this study aimed to investigate the effect of RD exercise on biomarkers of glycemic level including fasting plasma glucose (FPG), the 2 h oral glucose tolerance test (OGTT), hemoglobin A1C (HbA1C), the biomarkers of inflammation C-reactive protein (CRP) and interleukin 6 (IL-6), and body mass index (BMI) on prediabetes during 12-week RD exercise. A total of 64 participants were randomly assigned into two groups, RD and control (CON), and were tested by measuring their glycemic levels to screen for prediabetes. The RD group was instructed to perform 10 postures of RD exercise in 60 min, three times a week. The CON group received standard lifestyle recommendations that were not pharmacologically managed. The results reveal that the RD group experienced a significant decrease in FPG, OGTT, HbA1C, and IL-6 (p < 0.01), and BMI and CRP (p < 0.05) compared to the CON group. In addition, the CON group had considerably higher glycemic levels, BMI and IL-6 levels (p < 0.01). Our study demonstrates that RD could decrease the biomarkers of glycemic level and inflammation during 12 weeks of RD exercise in prediabetes. These findings suggest that RD exercise is an effective approach for reducing systemic inflammation and controlling glycemic levels in prediabetic patients.

Canagliflozin alters the gut, oral, and ocular surface microbiota of patients with type 2 diabetes mellitus.

Modifications in the gut microbiota may be a crucial factor in the efficacy of canagliflozin (Cana) in managing patients with type 2 diabetes mellitus (T2DM). However, the interplay between oral and ocular surface microbiota and this treatment remains poorly explored. This study aimed to assess alterations in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment in patients with T2DM. In this 30-day, controlled before-and-after study, 21 treatment-naïve patients with T2DM received sole treatment with Cana (100 mg/day), and were matched with 10 healthy controls based on gender and age. Using 16S rRNA sequencing, changes in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment were assessed and compared with those of healthy controls. Concurrently, diabetes-related clinical parameters were recorded over the study period. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR200034878). A noticeable shift was observed in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment. The post-Cana treatment gut microbiota was more similar to that of the healthy controls. Network correlation analysis revealed that modifications in the gut, oral, and ocular surface microbiota were related to changes in clinical parameters, especially for the ocular surface microbiota. A significant decrease in fasting plasma glucose (8.22 ± 2.19 vs 6.87 ± 1.09 mmol/L), glycated serum protein [291.00 (264.00, 353.00) vs 275.00 (251.00, 342.50) μmol/L], hemoglobin A1c (7.39 ± 1.18 vs 7.12 ± 1.33%), body mass index (25.32 ± 2.99 vs 24.83 ± 2.95 kg/m2), systolic blood pressure (129.05 ± 17.51 vs 123.43 ± 14.82 mmHg), and urinary creatinine [158.40 (74.75, 219.15) vs 79.70 (56.25, 138.10) μmmol/kg] levels was noted after 30-day Cana monotherapy (P < 0.05). Treatment with Cana resulted in an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria, particularly Lachnospiraceae UCG 004, Bacteroides, and Lachnospiraceae NK4A136 group. After Cana treatment, a significant increase of Prevotella and Veillonella, both of which are known to be closely associated with SCFAs, was observed. Post-Cana administration, the ocular surface microbiota exhibited the most distinct changes in structure and composition. Remarkably, the majority of the increased ocular surface microbiota could produce SCFAs within the gut microbiota. Cana effectively improved the dysregulated glucose metabolism in patients with T2DM. This improvement can potentially be attributed to the restoration of balance among the gut, oral, and ocular surface microbial communities. https://www.chictr.org.cn/showproj.html?proj=56487, identifier ChiCTR2000034878.

Efficacy and safety of glucagon-like peptide-1 receptor agonists therapy initiation in patients with type 2 diabetes hospitalized with coronavirus infection

BACKGROUND. The search for new effective methods of treatment and prevention of COVID-19 in patients with type 2 diabetes mellitus (T2DM) remains an urgent task for the healthcare system.AIM. To evaluate the efficacy and safety of initiating of glucagon-like peptide-1 receptor agonists (GLP-1RA) therapy in T2DM patients hospitalized with COVID-19.MATERIALS AND METHODS. The inclusion criteria were history of T2DM, BMI&gt; 27 kg/m2, confirmed diagnosis of COVID-19. The intervention group of 53 patients started dulaglutide therapy (1,5 mg once weekly) during the first 24 hours of admission, the control group consisted of 50 patients, who proceeded with glucose-lowering therapy. We evaluated the effect of therapy on carbohydrate metabolism, laboratory and clinical parameters, the outcome of COVID-19 and the safety of therapy (hypoglycemic events, side effects).RESULTS. There were no differences found in the degree of decrease in the level of glycemia in the compared groups: fasting plasma glucose (FPG) on day 7 of hospitalization– 8,2 [6,0;9,8] mmol/L vs 8,1 [6,5;9,8] mmol/L (p=0,935), mean daily glycemia (MDG) — 9,7 [8,3;11,8] mmol/L vs 11,1 [8,7;12,8] mmol/L (p=0,182). Therapy of dulaglutide had a positive effect on inflammatory markers: CRP (15,8 vs 24,4 mg/l, p=0,035), LDH (261,6 vs 326,1 U/l, p=0,016) and the level of lymphocytes (1,2 vs 0,9 x 10*9/L, p=0,049) and on clinical parameters: saturation, the need for oxygen therapy and the risk of severe course according to the NEWS2 scale. The death rate in the group receiving GLP-1RA is 3,5 times lower compared to the control group (5,7% vs 20,0%, p=0,038). The initiation of dulaglutide therapy in patients with T2DM hospitalized with COVID-19 reduced the chance of death and transfer to mechanical ventilation by 4,2 times compared to the control group (OR = 0,24, 95% CI: 0,062–0,931). GLP-1RA therapy in patients with COVID-19 and T2DM is safe in terms of hypoglycemic events and side effects.CONCLUSIONS. The initiation of GLP-1RA therapy leads to a decrease in FPG and MDG, comparable with the control group. The start of GLP-1RA therapy in hospitalized patients with COVID-19 and T2DM reduces the chance of death, favorably affecting on laboratory and clinical parameters.

BMI change during childhood, DNA methylation change at TXNIP, and glucose change during midlife.

This study investigated whether changes in DNA methylation (DNAm) at TXNIP are associated with glycemic changes and whether such an association differs with early-life adiposity changes. A total of 594 Bogalusa Heart Study participants who had blood DNAm measurements at two time points in midlife were included. Of them, 353 participants had at least four BMI measurements during childhood and adolescence. The incremental area under the curve was calculated as a measure of long-term trends of BMI during childhood and adolescence. Increase in DNAm at TXNIP was significantly associated with decrease in fasting plasma glucose (FPG) independent of covariates (p < 0.001). The study found that the strength of this relationship was significantly modified by a trend of increasing BMI during childhood and adolescence (p-interaction = 0.003). Each 1% increase in DNAm at TXNIP was associated with a 2.90- (0.77) mg/dL decrease in FPG among participants with the highest tertile of BMI incremental area under the curveand a 0.96- (0.38) mg/dL decrease among those with the middle tertile, whereas no association was observed among participants with the lowest tertile. These results indicate that changes in blood DNAm at TXNIP are significantly associated with changes in FPG in midlife, and this association was modified by BMI trendsduring childhood and adolescence.

1546-P: Gut-Specific Neprilysin Deletion Increases Insulin Secretion in High-Fat–Fed Mice

Global deletion of the ubiquitous peptidase neprilysin (NEP) protects against high fat diet (HFD)-induced insulin secretory dysfunction. Since NEP is expressed in the gut, it can cleave locally produced insulinotropic peptides. We previously found that under physiological conditions, acute inhibition of gut NEP enhances glucose-stimulated insulin secretion (GSIS) in mice. Thus, we determined whether this beneficial effect on GSIS also occurs in mice with gut-specific NEP deletion that are fed HFD. Mice with conditional deletion of NEP in enterocytes (NEPGut-/-) were generated by crossing Vil1-cre and floxed NEP mice. NEP activity was almost abolished throughout the gut in NEPGut-/- vs control mice (5±2 vs 164±20 vs 120±20 pmol MNA/h/μg, NEP Gut-/- vs Vil1-cre vs NEPfl/fl mice; n=5-6/group; p&amp;lt;0.0001), and was similar in plasma, pancreas and kidney among all mice. At 11 weeks of age, mice were fed HFD for 14 weeks, after which an OGTT was performed and GSIS assessed as ∆insulin/∆glucose from 0 to 10 min. Despite similar body weights in NEP Gut-/- and control mice, fasting plasma glucose was lower and GSIS higher in NEP Gut-/- vs controls (Table). In sum, gut-specific NEP deletion decreases fasting plasma glucose and increases GSIS in HFD-fed mice, suggesting gut NEP impairs ß-cell function under conditions of HFD. Thus, strategies to inhibit NEP specifically in the gut may protect against fat-induced ß-cell dysfunction. Disclosure N.Esser: None. S.M.Mongovin: None. B.Barrow: None. S.Zraika: None. Funding National Institutes of Health (DK098506, (P30DK017047)

Effect of "maccog" TCM tea on improving glucolipid metabolism and gut microbiota in patients with type 2 diabetes in community.

This work aimed to observe the effect of consuming Chinese herb tea on glucolipid metabolism and gut microbiota in patients with type 2 diabetes mellitus (T2DM). Ninety patients with T2DM were recruited from a community and randomly divided into the control group (CG) and intervention group (IG). CG maintained conventional treatment and lifestyle, and IG accepted additional "maccog" traditional Chinese medicine (TCM) tea (mulberry leaf, radix astragali, corn stigma, cortex lycii, radix ophiopogonis, and gynostemma) for 12 weeks. Glucolipid metabolism, hepatorenal function, and gut microbiota were then measured. After the intervention, the decreases in fasting plasma glucose (FPG) and total cholesterol (TC) were greater (P<0.05) in IG than in CG, and those in glycosylated serum protein (GSP) were almost significantly greater (P=0.066) in IG than in CG. The total protein (TP), albumin (ALB), and creatinine (CREA) levels in IG were significantly lower and their decreases were larger in IG than in CG (P<0.05) after the intervention. The Ace and Chao1 indices in IG were slightly higher after the intervention (P=0.056 and 0.052, respectively) than at baselines. The abundance of Actinobacteria, Lachnospiraceae, Bifidobacteriaceae, and Phascolarctobacterium increased significantly after the intervention in IG (P<0.05), and the abundance was higher in IG than in CG (P<0.05 or P<0.1). The abundance of Clostridiales and Lactobacillales was negatively correlated with FPG (P<0.05), Clostridiales and Lachnospiraceae was negatively correlated with GSP (P<0.05), and Bacteroides/Firmicutes was positively correlated with both (P<0.05). No adverse event was observed during the intervention. Administration of "maccog" TCM tea for 12 weeks slightly improved glucolipid metabolism and significantly increased the abundance of beneficial gut microbiota in community patients with T2DM. The increase in beneficial bacteria abundance may be involved in the improvement of glucose metabolism indicators. In addition, this intervention is safe and feasible. https://www.chictr.org.cn/showproj.aspx?proj=31281, identifier ChiCTR1800018566.

Efficacy and safety of janagliflozin monotherapy in Chinese patients with type 2 diabetes mellitus inadequately controlled on diet and exercise: A multicentre, randomized, double-blind, placebo-controlled, Phase 3 trial.

To evaluate the efficacy and safety of janagliflozin, a selective renal sodium-glucose cotransporter-2 inhibitor, as monotherapy in drug-naive Chinese patients with type 2 diabetes mellitus (T2DM). This Phase 3 trial included a 24-week, multicentre, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. A total of 432 patients with glycated haemoglobin (HbA1c) levels ≥7.0% (53 mmol/mol) and ≤10.5% (91 mmol/mol) were randomized (1:1:1) to receive once-daily placebo, 25 mg or 50 mg janagliflozin. After 24 weeks, patients on placebo were switched and re-randomized (1:1) to 25 mg or 50 mg janagliflozin, whereas patients on janagliflozin maintained the initial therapy. The primary endpoint was change from baseline in HbA1c after 24 weeks. At Week 24, the placebo-adjusted least squares mean changes in HbA1c were -0.80%(95% confidence interval [CI] -0.98%to -0.62%)/-8.7mmol/mol(95%CI-10.7mmol/molto-6.8mmol/mol) and -0.88% (95% CI -1.06% to -0.70%)/-9.6 mmol/mol (95% CI -11.6mmol/molto-7.7mmol/mol), respectively (P <0.001 for both). A higher proportion of patients achieved HbA1c <7.0% (53 mmol/mol) with janagliflozin 25 mg and janagliflozin 50 mg compared with placebo (47.2%, 49.3%, and 23.5%, respectively). Both janagliflozin doses significantly decreased fasting plasma glucose, 2-hour postprandial glucose, body weight and systolic blood pressure, as well as increased high-density lipoprotein (HDL) cholesterol and insulin sensitivity compared with placebo (P <0.05 for all). The trends in improvement of these variables were sustained during the 28-week extension period. Overall incidences of adverse events were 67.8%, 71.5% and 60.7% with janagliflozin 25 mg, janagliflozin 50 mg and placebo, respectively. The incidence of urinary tract infections and genital fungal infections was low. No severe hypoglycaemia or ketoacidosis occurred. Janagliflozin 25 mg and 50 mg monotherapy once-daily effectively improved glycaemic control, reduced body weight and blood pressure, improved HDL cholesterol and insulin sensitivity, and was generally well tolerated.

Glycemic disorders in patients with pheochromocytomas and sympathetic paragangliomas.

The objective of our study was to determine the prevalence of glycemic disorders (diabetes mellitus and prediabetes) in patients with pheochromocytomas and sympathetic paragangliomas (PPGLs) and identify risk factors for their development and the likelihood of their resolution after surgery. A multicentric retrospective study of patients with PPGLs submitted to surgery between 2000 and 2021 in 17 Spanish hospitals was performed. Diabetes-specific data were collected at diagnosis, in the immediate- and long-term postsurgical follow-up. A total of 229 patients with PPGLs were included (218 with pheochromocytomas and 11 with sympathetic paragangliomas). Before surgery, glycemic disorders were diagnosed in 35.4% of the patients (n = 81): 54 with diabetes and 27 with prediabetes. The variables independently associated with a higher risk of glycemic disorders were sporadic PPGL (odds ratio (OR) = 3.26 (1.14-9.36)) and hypertension (OR = 3.14 (1.09-9.01)). A significant decrease in fasting plasma glucose and HbA1c levels was observed after surgery, in the short-term and long-term follow-up (P < 0.001). After a median follow-up of 48.5 months (range 3.3-168.9), after surgery, 52% of diabetic and 68% of prediabetic patients experienced a complete resolution. Lower body mass index (BMI) (P = 0.001), lower glucose levels (P = 0.047) and shorter duration of diabetes prior to surgery (P = 0.021) were associated with a higher probability of diabetes resolution. In conclusion, glycemic disorders in patients with PPGLs are present in more than a third of them at diagnosis. Sporadic PPGLs and hypertension are risk factors for their development. More than 50% of cases experience a complete resolution of the glycemic disorder after resection of the PPGLs.

Association of fasting plasma glucose trajectory with lifetime risk of cardiovascular disease.

Few studies have used multiple measurements of fasting plasma glucose (FPG) to examine the impact of long-term FPG trajectory patterns on lifetime risk of cardiovascular disease (CVD). We aimed to identify the long-term patterns in FPG trajectories and to estimate the lifetime risk of CVD according to FPG trajectories. Individuals free of CVD at index ages 35 (n = 72,324), 45 (n = 62,049), and 55 (n = 38,113) years were included. FPG concentrations were measured in 2006, 2008, and 2010. The FPG trajectories were identified by latent mixture modeling. The modified Kaplan-Meier method was used to calculate lifetime risk of CVD. We identified five distinct FPG trajectories and named them according to FPG range and changing pattern over time: low-stable, moderate-stable, moderate-increasing, elevated-decreasing, and elevated-stable. At index age 35 years, we documented 3110 CVD events in men during 371,219 person-years of follow-up and 357 CVD events in women during 107,447 person-years of follow-up. Among all participants, the elevated-stable FPG pattern experienced the highest lifetime risk of CVD (44.8%, 95% CI: 37.8-51.9%), low-stable pattern was lowest (24.3%, 95% CI: 23.3-25.2%). At index age 55 years, although the elevated-stable and elevated-decreasing FPG patterns had similar original FPG concentrations, individuals with elevated-decreasing pattern (30.0%, 95% CI: 23.9-36.1%) had approximately one-third less lifetime risk of CVD than those with elevated-stable pattern (43.6%, 95% CI: 31.8-55.3%). FPG trajectories were significantly associated with the lifetime risk of CVD. Both decrease in FPG over time and consistently lower FPG over 4 years were associated with lower lifetime risk of CVD.

Potential for sodium-glucose cotransporter-2 inhibitors in the management of metabolic syndrome: A systematic review and meta-analysis.

Landmark trials have established the benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) in cardiovascular disease including heart failure with reduced and preserved ejection fraction and renal diseases regardless of the presence of diabetes mellitus. However, studies evaluating the role of SGLT2-Is in metabolic syndrome (MetS) are limited. This study primarily aimed to evaluate the impact of SGLT2-Is on the components of MetS. Two independent reviewers and an experienced librarian searched Medline, Scopus and the Cochrane central from inception to December 9, 2021 to identify placebo controlled randomized controlled trials that evaluated the impact of SGLT2-Is on the components of MetS as an endpoint. Pre- and post-treatment data of each component were obtained. A meta-analysis was performed using the RevMan (version 5.3; Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration). Treatment with SGLT2-Is resulted in a decrease in fasting plasma glucose (-18.07 mg/dL; 95%CI: -25.32 to -10.82), systolic blood pressure (-1.37 mmHg; 95%CI: -2.08 to -0.65), and waist circumference (-1.28 cm; 95%CI: -1.39 to -1.18) compared to placebo. The impact on high-density lipoprotein cholesterol was similar to placebo (0.01 mg/dL; 95%CI: -0.05 to 0.07). SGLT2-Is have a promising role in the management of MetS.

Use of a bio-electronic device comprising of targeted dual neuromodulation of the hepatic and celiac vagal branches demonstrated enhanced glycemic control in a type 2 diabetic rat model as well as in an Alloxan treated swine model.

There is an unmet need for new type 2 diabetes treatments providing improved efficacy, durability and customized to improve patient's compliance. Bio-electronic neuromodulation of Vagus nerve branches innervating organs that regulate plasma glucose, may be a method for treating type 2 diabetes. The pancreas has been shown to release insulin during Vagus stimulation. The hepatic vagal branch, innervating the liver, has been shown to decrease glucose release and decrease insulin resistance following ligation. However, standalone stimulation of the Vagus nerve has shown mixed results and Vagus nerve ligation has undesirable effects. Little is known; however, of the effect on plasma glucose with combined neuromodulation consisting of stimulation of the celiac branch innervating the pancreas with simultaneous high frequency alternating current (HFAC) blockade of the hepatic branch. This study tested the effects of this approach on increasing glycemic control in rat a model of type 2 diabetes and Alloxan treated swine. Zucker obese (fatty) male rats (ZDF fa/fa) were used as a model of type 2 diabetes as well as glucose intolerant Alloxan treated swine. In ZDF rat experiments glycemic control was accessed with an intravenous glucose tolerance test during HFAC-induced hepatic branch block with concurrent celiac stimulation (HFAC + stimulation). In swine experiments glycemic control was accessed by an oral glucose tolerance test during HFAC + stimulation. Insulin measurements were taken prior to and following swine experiments giving insight into beta cell exhaustion. Histopathology was conducted to determine safety of HFAC + stimulation on Vagal branches. Zucker rats demonstrated a significant improvement to an intravenous glucose tolerance test during HFAC + stimulation compared to sham. There was no significant difference from sham compared to hepatic vagotomy or celiac stimulation. In Alloxan treated swine, when subjected to HFAC + stimulation, there was a significant improvement in glycemic control as measured by an improvement on oral glucose tolerance tests and a decrease in fasting plasma glucose. Insulin responses were similar prior to and following HFAC + stimulation experiments. Histopathology demonstrated healthy swine Vagus nerves. Electrical blockade of the hepatic Vagus branch with simultaneous stimulation of the celiac Vagus branch may be a novel, adjustable and localized approach for a treatment of type 2 diabetes.

The Paradoxical Role of Circulating Ketone Bodies in Glycemic Control of Individuals with Type 2 Diabetes: High Risk, High Reward?

Introduction: Fasting plasma ketone bodies (KB) are elevated in individuals with type 2 diabetes (T2D) and could affect glycemic control and disease progression. Prolonged KB exposure may result in adaptive beneficial responses, counteracting glycemic dysregulation. In the current proof-of-concept study in adults with T2D, we hypothesized that fasting plasma KB are cross-sectionally associated with poorer glycemic control but prospectively with better glycemic control. Materials and Methods: Fasting plasma KB were measured via nuclear magnetic resonance spectroscopy in patients with T2D treated in primary care (Zodiac cohort; The Netherlands). We analyzed the associations between KB and HbA1c at baseline using linear regression analyses and HbA1c changes over time using linear mixed models. We adjusted for potential confounders, including risk factors for poor glycemic control. Individuals with T2D participating in the general population-based PREVEND study were used as a replication cohort. Results: We included 271 individuals with T2D with a total of 859 HbA1c measurements during a follow-up period of 3.0 (2.0–3.2) years. At baseline, the total amount of fasting plasma KB was independently and positively associated with HbA1c levels (regression coefficient in the fully adjusted analysis = 0.31; 95% CI 0.06–0.57, per doubling of KB; p = 0.02). In contrast, in the longitudinal analyses, fasting plasma KB were associated with a yearly HbA1c (%) decrease of −0.10 (95% CI −0.19 to −0.00 per doubling baseline KB; p = 0.05). Results were replicated in 387 individuals with T2D from a general population cohort with a total of 1115 glucose measurements during a follow-up period of 7.5 (7.2–8.0) years. A yearly decrease in fasting plasma glucose (mmol/L) of 0.09 was found per doubling of baseline KB. Conclusions: This study is the first to suggest a paradoxical role of circulating KB on glycemic control in T2D: elevated KB are associated with cross-sectionally poorer glycemic control but longitudinally with better long-term glycemic control.

Effects of nutrition on metabolic and endocrine outcomes in women with polycystic ovary syndrome: an umbrella review of meta-analyses of randomized controlled trials.

Numerous meta-analyses have been conducted on the effects of nutritional interventions on various health outcomes in women with polycystic ovary syndrome (PCOS). However, the strength of the evidence and its clinical significance are unclear. This umbrella review aimed to summarize the effects of nutritional interventions on women with PCOS and assess the strength of the evidence. PubMed, Scopus, and Web of Science were searched from inception until March 17, 2021. Meta-analyses of randomized clinical trials (RCTs) that examined the impact of dietary modifications or supplementations on women with PCOS were selected. Data extraction, quality assessments of the meta-analyses, and evaluation of the strength of the evidence were conducted independently by 2 investigators and confirmed by a third. Twenty-eight RCT meta-analyses were included, reporting 40 different outcomes. Lower carbohydrate, Dietary Approaches to Stop Hypertension, or lower glycemic index/load diets in women with PCOS significantly improved some anthropometric and metabolic characteristics (with very low to low certainty). Probiotics/synbiotics reduced fasting plasma glucose, fasting insulin (FI), and homeostasis model assessment-estimated insulin resistance (HOMA-IR) (with moderate to high certainty). Curcumin supplementation decreased fasting plasma glucose, FI, and HOMA-IR (with moderate certainty). Fish oil supplementation decreased FI and HOMA-IR, and omega-3 reduced triglycerides (with moderate certainty). There were also improvements in FI after taking vitamin D or inositol supplements (with moderate certainty). Supplementation with fish oil increased adiponectin (with high certainty), and probiotics/synbiotics reduced total testosterone (with moderate certainty). In subfertile women with PCOS, inositol increased the ovulation rates (with moderate certainty). There was no high-certainty evidence that diets alone in women with PCOS improved health or reproductive outcomes. Supplementation with vitamin D, probiotics/synbiotics, omega-3, inositol, and curcumin showed favorable effects on some metabolic outcomes. Probiotics/synbiotics possibly reduces total testosterone, and inositol stimulates ovulation in women with PCOS. PROSPERO registration no. CRD42021251496.

A Randomized Controlled Trial of R-Form Verapamil Added to Ongoing Metformin Therapy in Patients with Type 2 Diabetes

ContextThere is a medical need for effective insulin-independent antidiabetic drugs that can promote pancreatic β-cell function and have a low risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients. R-form verapamil (R-Vera), which is able to enhance the survival of β-cells and has higher cardiovascular safety margin compared with racemic verapamil, was developed as a novel approach for T2DM treatment.ObjectiveThis randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of 3 dosages of R-Vera added to ongoing metformin therapy in T2DM patients who had inadequate glycemic control on metformin alone.MethodsParticipants were randomly assigned in an equal ratio to receive R-Vera 450, 300, or 150 mg per day, or matching placebo, in combination with metformin. The primary endpoint was change in hemoglobin A1c (HbA1c) after 12 weeks of treatment.ResultsA total of 184 eligible participants were randomized to receive either R-Vera or placebo plus metformin. At week 12, significant reductions in HbA1c were observed for R-Vera 300 mg/day (−0.36, P = 0.0373) and 450 mg/day (−0.45, P = 0.0098) compared with placebo. The reduction in HbA1c correlated with decreasing fasting plasma glucose levels and improved HOMA2-β score. Treatment with R-Vera was well tolerated with no hypoglycemic episodes occurring during the trial.ConclusionAddition of R-Vera twice daily to ongoing metformin therapy significantly improved glycemic control in T2DM patients. The favorable efficacy and safety profile of R-Vera 300 mg/day can be considered as the appropriate dose for clinical practice.

Effects of exercise on NAFLD using non-targeted metabolomics in adipose tissue, plasma, urine, and stool

The mechanisms by which exercise benefits patients with non-alcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, remain poorly understood. A non-targeted liquid chromatography-mass spectrometry (LC–MS)-based metabolomics analysis was used to identify metabolic changes associated with NAFLD in humans upon exercise intervention (without diet change) across four different sample types—adipose tissue (AT), plasma, urine, and stool. Altogether, 46 subjects with NAFLD participated in this randomized controlled intervention study. The intervention group (n = 21) performed high-intensity interval training (HIIT) for 12 weeks while the control group (n = 25) kept their sedentary lifestyle. The participants' clinical parameters and metabolic profiles were compared between baseline and endpoint. HIIT significantly decreased fasting plasma glucose concentration (p = 0.027) and waist circumference (p = 0.028); and increased maximum oxygen consumption rate and maximum achieved workload (p < 0.001). HIIT resulted in sample-type-specific metabolite changes, including accumulation of amino acids and their derivatives in AT and plasma, while decreasing in urine and stool. Moreover, many of the metabolite level changes especially in the AT were correlated with the clinical parameters monitored during the intervention. In addition, certain lipids increased in plasma and decreased in the stool. Glyco-conjugated bile acids decreased in AT and urine. The 12-week HIIT exercise intervention has beneficial ameliorating effects in NAFLD subjects on a whole-body level, even without dietary changes and weight loss. The metabolomics analysis applied to the four different sample matrices provided an overall view on several metabolic pathways that had tissue-type specific changes after HIIT intervention in subjects with NAFLD. The results highlight especially the role of AT in responding to the HIIT challenge, and suggest that altered amino acid metabolism in AT might play a critical role in e.g. improving fasting plasma glucose concentration.Trial registration ClinicalTrials.gov (NCT03995056).

The Effects of Probiotic Supplementation on Opioid-Related Disorder in Patients under Methadone Maintenance Treatment Programs.

Introduction Patients under methadone maintenance treatment programs (MMTPs) are susceptible to numerous complications (e.g., mental and metabolic disorders). This study evaluated the effects of probiotics on clinical symptoms, biomarkers of oxidative stress, inflammation, insulin resistance, and serum lipid content in patients receiving MMTPs. Materials and Methods A randomized, double-blind, placebo-controlled trial was conducted among 70 patients receiving MMTPs to receive either 1.8 × 109 CFU/day probiotics (n = 35) or placebo (n = 35) for 12 weeks. Clinical symptoms and metabolic profiles were measured before and after the intervention in patients receiving MMTPs. Results Compared with the placebo group, probiotic supplementation resulted in a significant improvement in the severity of depression (P < 0.05). In addition, probiotic administration significantly decreased fasting plasma glucose (FPG), total cholesterol, and low-density lipoprotein cholesterol (LDL cholesterol) (P < 0.05). Furthermore, probiotics resulted in a significant reduction in high-sensitivity C-reactive protein (hs-CRP) and a significant elevation in total antioxidant capacity (TAC) and total glutathione (GSH) levels (P < 0.05). Conclusion Treatment with probiotics for 12 weeks to patients receiving MMTPs had beneficial effects on symptoms of depression, as well as several metabolic profiles. Clinical Trial Registration: this study was registered in the Iranian website (https://www.irct.ir) for clinical trials registration (https://fa.irct.ir/trial/46363/IRCT20170420033551N9). The registration date is March 22, 2020.

Metabolic and Anthropometric Parameters of Persons at Risk of Developing Type 2 Diabetes Mellitus Before and After 3 Months of Consuming Insoluble Dietary Fiber.

Background:Observational studies have shown that insoluble fiber (IF) can be effective in preventing type 2 diabetes (T2D), but there is a lack of experimental data on the effect of short-term consumption of IF on metabolic parameters. We tried to investigate whether there was an improvement in glycemia and body composition in individuals at risk for T2D after 3 months of IF consumption.Methods:This “Type 2 Diabetes Mellitus Prevention Ukraine (T2DPUA)” study describes participants with impaired fasting glucose (IFG) as determined by ADA criteria. The study involved 30 people, including 21 women (70%). Daily, 15 g of IF derived from wheat was used. T2DPUA did not have a placebo group and the intervention lasted 3 months. Evaluation of fasting plasma glucose (FPG) and 2h plasma glucose (2hPG), glycated hemoglobin (HbA1c), total cholesterol, HDL-cholesterol, triacylglycerols, uric acid, and γ-glutamyl transferase was performed. The baseline and 3-monthly anthropometric examinations included measurements of weight, waist and hip circumference. Fat mass was assessed by bioelectrical impedance analysis. Paired samples t-test or Wilcoxon test were used.Result:A decrease of FPG (P = .042), HbA1c (P < .001), 2hPG (P = .005), weight (P < .001), body mass index (P < .001), the proportion of body fat (P = .006), and the absolute amount of fat (P < .001), increases in systolic (P < .001) and diastolic (P = .008) blood pressure was shown. The number of people with hypertension did not change. The absolute amount of body fat decreased by almost 5% and tolerance to the standard glucose load improved by 15%. The dynamics of other metabolic parameters were not revealed.Conclusion and Recommendation:Data about improvement of glycemia and body composition over a short period of using IF by individuals with IFG are new and deserve larger studies.