Changes In Plasma Glucose Research Articles

Influence of Acute Fasting on Cerebrovascular Reactivity During Mental Stress

Acute fasting has been adopted in fitness communities, and has been practiced for religious purposes. Short‐term fasting does not affect cognitive function, and therefore may not affect cerebrovascular responsiveness. Cerebral blood flow velocity increases with mental stress, however the combined influences of an acute fast and mental stress on cerebrovascular responses are unknown. The purpose of this study was to describe the effects of a 24‐hour, water‐only fast on cerebral blood flow velocity responses to mental stress in a small cohort of research volunteers. Eight young healthy participants (7 males, average age of 25 yrs) completed the protocol in a fed state (4 hours post‐prandial) and in a fasted state (24–25 hours post‐prandial). Whole blood was collected and analyzed before experimentation for β‐Ketones, total cholesterol, HDL, LDL, triglycerides (TRG), and glucose. With participants in a supine position, we recorded the electrocardiogram, beat‐to‐beat arterial pressure (finger plethysmography), and cerebral artery blood flow velocity (transcranial Doppler). After a 5‐min baseline, participants performed 5‐min of mental stress via mental arithmetic (rapid continuous subtraction). Mental stress reactivity was calculated as the mean stress response for each minute of mental stress minus the corresponding 5‐min baseline. The minute‐by‐minute reactivity was analyzed with repeated measures ANOVA. Blood variables were analyzed with paired t‐tests. Data were expressed as mean ± SE. Baseline blood variables were different in the fasted compared with the fed state: TRG (112±14 fed vs. 68±13 mg/dL fasted; p<.01) Glucose (101±5 fed vs. 79±6 mg/dL fasted; p<.01) and β‐Ketone (.1±.01 fed vs. .5±.2 mmol/L fasted; p<.05). Mean arterial pressures and heart rate reactivities to mental stress were not affected by fasting. Mean cerebral blood flow velocity reactivity to mental stress was reduced in the fasted compared with the fed condition (condition × time, p<.01), with a particular divergent responsiveness during the third minute of mental stress. The results we present are new, but preliminary. We did not attempt to ascribe mechanisms to fasting and cerebral blood flow velocity reactivity during mental stress. The changes we observed with our preliminary data set suggest that fasting, and associated changes of plasma glucose, β‐Ketone and TRG may be associated with reductions of cerebral blood flow velocity during mental stress.Support or Funding InformationSupport was provided by the Michigan Space Grant Consortium and The Portage Health Foundation of Michigan.

Efficacy and safety of generic exenatide injection in Chinese patients with type 2 diabetes: a multicenter, randomized, controlled, non-inferiority trial.

This study aimed to compare the efficacy and safety of generic exenatide with branded exenatide Byetta® in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on monotherapy or combination therapy of metformin and insulin secretagogues. A multicenter, randomized, controlled, non-inferiority trial was performed. A total of 240 patients with T2DM and glycated hemoglobin (HbA1c) ≥ 7% (53mmol/mol) to ≤ 9.0% (75mmol/mol) on monotherapy or combination therapy of metformin and insulin secretagogues for at least 3months were randomized into generic exenatide or branded exenatide groups with a 1:1 ratio for 16weeks of treatment. The primary endpoint was the change in HbA1c levels from baseline at week 16, with a non-inferiority margin of - 0.35%(-3.83mmol/mol) (lower bound of one-sided 95% confidence interval (CI) > - 0.35% (-3.83mmol/mol)). Secondary endpoints included the proportion of participants achieving HbA1c < 7% (53mmol/mol), the changes in fasting plasma glucose (FPG), 2-h postprandial glucose (2hPG) following a standard meal, 7-point self-monitoring blood glucose (SMBG) profiles, body weight change from baseline at week 16 and the change in HbA1c levels from baseline at week 8. Safety issues were also evaluated. After 16weeks of treatment, HbA1c levels decreased significantly from baseline in the two groups, with a reduction of - 1.10% ± 1.31% (- 12.0mmol/mol ± 14.3mmol/mol) in the generic exenatide group and - 1.08% ± 1.11% (- 11.8mmol/mol ± 12.1mmol/mol) in the branded exenatide group (both P < 0.001). The least-squares mean difference of HbA1c reduction between the two groups was - 0.03% (- 0.33mmol/mol), with a lower one-sided 95% CI limit of - 0.27% (- 2.95mmol/mol), which was higher than the prespecified non-inferiority margin of - 0.35% (- 3.83mmol/mol). Moreover, there were no significant differences in the proportion of participants achieving HbA1c < 7% (53mmol/mol) and the changes in FPG, 2hPG, 7-point SMBG profiles and body weight at week 16 and the change in HbA1c levels from baseline at week 8 (all P > 0.05) between the two groups. The incidence of adverse events, including the incidence of hypoglycemia (18.3% and 17.5%, respectively), was similar for the generic and branded exenatide groups (P > 0.05). In patients with T2DM inadequately controlled on monotherapy or combination therapy of metformin and insulin secretagogues, add-on treatment with generic exenatide demonstrated non-inferiority to branded exenatide in terms of improvements in HbA1c after 16weeks of treatment. Furthermore, the two drugs were also similar for other efficacy endpoints and safety profile. Trial registration Chinese Clinical Trial Registry: ChiCTR-IPR-15006558, Date registered May 27, 2015.

Thiazide Diuretic-Induced Change in Fasting Plasma Glucose: a Meta-analysis of Randomized Clinical Trials.

Prior meta-analyses measuring thiazide-induced glycemic change have demonstrated an increased risk of incident diabetes; however, this measure's definition has changed over time. To determine the magnitude of change in fasting plasma glucose (FPG) for thiazide diuretics. A research librarian designed and conducted searches in Medline®, EMBASE, and EBM Reviews-Cochrane Central Register of Controlled Trials (inception through July 2018) and International Pharmaceutical Abstracts (inception to December 2014). Randomized, controlled trials comparing a thiazide or thiazide-like diuretic to any comparator reporting FPG were identified. Trials enrolling < 50 participants, those with a follow-up period of < 4weeks, and conference abstracts were excluded. Independent duplicate screening of citations and full-text articles, data extraction, and assessment of risk of bias was conducted. Ninety-five studies were included (N = 76,608 participants), with thiazides compared with placebo, beta-blockers, calcium channel blockers, renin-angiotensin-aldosterone-system inhibitors, potassium-sparing diuretic, and others alone or in combination. Thiazide diuretics marginally increased FPG (weighted mean difference 0.20mmol/L (95% CI 0.15-0.25); I2= 84%) (1mmol/L = 18mg/dL). Results did not change substantially when considering dose or duration, comparing thiazides with placebo or an active comparator, or using thiazides as monotherapy or combination therapy, even when combined with a potassium-correcting agent. Thiazide diuretics have a small and clinically unimportant impact on FPG.

Five-Year Glycemic Trajectories Among Healthy African-American and European-American Offspring of Parents With Type 2 Diabetes

Cross-sectional surveys report a higher prevalence of diagnosed type 2 diabetes mellitus (T2DM) in African Americans (AA) than European Americans (EA). We studied 5-year glycemic excursions among AA and EA in the Pathobiology of Prediabetes in A Biracial Cohort study, to assess ethnic disparities. Pathobiology of Prediabetes in A Biracial Cohort followed normoglycemic offspring of parents with T2DM for 5 years, with serial assessments of oral glucose tolerance test , anthropometry, body fat, insulin sensitivity and beta-cell function. The primary outcome was progression to prediabetes (impaired fasting glucose and/or impaired glucose tolerance). We further analyzed 5-year changes in fasting (FPG) and 2-hour plasma glucose (2hrPG). One hundred and one (52 AA, 49 EA) out of 343 subjects developed prediabetes during follow-up. The change in FPG ranged from -24 mg/dl to +38 mg/dl. The FPG remained stable (± 5 mg/dl from baseline) in 50% of EA and 46.8% of AA and the 2hrPG remained stable (± 25 mg/dl from baseline) in 73.7% of EA and 71.0 % of AA during follow-up. The proportions with change in FPG of 5mg/dl to >25 mg/dl and 2hrPG of 25 mg/dl to >50 mg/dl were similar in EA and AA offspring, as were the 10th - 90th percentiles of the distribution of 5-year changes in FPG and 2hrPG. During 5 years of follow-up, black and white offspring of parents with T2DM exhibited remarkable phenotypic concordance of glycemic trajectories. Thus, parental history of T2DM may be a stronger factor than race/ethnicity in the prediction of longitudinal glycemic trends.

Gender Differences in the Response to Short-term Cold Exposure in Young Adults.

Cold exposure (CE) has been shown to enhance energy expenditure by activating brown adipose tissue thermogenesis and metabolism in humans. However, it remains to be elucidated if there are gender-specific differences in cold-induced thermogenesis and metabolism. To study the impact of mild CE on resting energy expenditure (REE) and metabolism in males compared with females. A cross-sectional study. 117 healthy young Caucasians participated in this study (58 males). Mean age was 25.1 ± 3.6 years and mean body mass index 22.3 ± 1.7 kg/m2. Participants underwent a short-term CE using water perfused mattresses to activate nonshivering thermogenesis. REE was assessed before and 2 hours after CE followed by blood sampling. Selected metabolites and hormones were measured. Skin temperatures were monitored at various sites throughout the experiment. Participants showed a significant increase in REE after CE (6.5%, P < .001). This increase did not differ between genders (P = .908). However, there were differences between males and females in changes of plasma glucose (-5.1% versus -7.4%, P = .024), leptin (-14.3% versus -30.1%, P < .001) and adiponectin (5.4% versus 12.8%, P = .018) after CE. We observed a significant decrease of the supraclavicular skin temperature in men (-0.3%, P = .034), but not in women (0.3%, P = .326)(P = .019 between genders). We did not observe a difference in the thermogenic response, measured as change of REE, to CE in women compared with men. However, we found that some metabolic and hormonal changes were more pronounced in women than in men suggesting a gender-specific response to cold.

Abstract 22: Novel Plasma Lipids Predict Risk of Diabetes: A Longitudinal Lipidomics Study in American Indians

Background: American Indians (AIs) suffer disproportionately high rate of type 2 diabetes (T2D). Traditional biomarkers have limited value in predicting and tracking early onset and progression of T2D. There is an urgent need for early biomarkers in this high-risk but understudied minority population. Objective: To identify novel lipids predictive of T2D onset among American Indians, independent of standard risk factors. Methods: We studied 2,000 American Indians attending two clinical exams (2001-2003, 2006-2009, average 5-yr apart) in the Strong Heart Family Study (SHFS). Fasting plasma lipids were repeatedly measured by untargeted lipidomics using LC-MS/MS. All participants were free of overt CVD at baseline (2001-2003) and followed through 2017 (average 16-yr follow-up). Cox regression with frailty model was used to identify lipids predictive of T2D onset, adjusting for traditional risk factors including age, sex, smoking, BMI, triglyceride, HDL, insulin resistance, eGFR and dietary intake of protein. Longitudinal analysis was conducted by regressing changes in lipids on changes in T2D-related traits (e.g., fasting glucose, HbA1c, or insulin resistance) between baseline and 5-yr follow-up, adjusting for changes in BMI, triglyceride, HDL, and eGFR. Incremental prognostic value of lipids in diabetes risk prediction above traditional risk factors was estimated using area under the curve (AUC). Network analysis was conducted to examine the dynamic changes in lipid networks between baseline and 5-yr follow-up. Multiple testing was controlled by FDR. Results: Of 1,628 non-diabetic participants at baseline (mean age 39.8, 62% women), 189 and 359 individuals developed incident T2D after 5-yr and 16-yr follow-up, respectively. Our high-resolution lipidomics detected 1,826 lipids, of which 1,119 lipids (460 known, 659 unknown) passed stringent quality control. Seven lipids with known structures significantly predict over 30% increased (FA(18:1), FA(20:2), FA(22:2), SM(d34:0) ) or 19% decreased (PC(37:4), PC(37:5), PC(38:4)) risk of T2D onset at both follow-ups. Nine unknown lipids also predicted T2D onset. Longitudinal changes in CE(20:2), CE(22:6), PC(32:0) and two unknowns explain about 6.4% changes in fasting plasma glucose. These newly identified lipids significantly improve the performance of risk prediction over traditional risk factors (AUC increased from 0.787 to 0.803, P=0.002). Network topology analysis revealed that the network connectivity among lipids was much stronger in participants who developed new T2D compared to those who didn’t (degree of network connectivity, 4.2 vs 2.5, P&lt;0.001). Conclusion: We identified several novel plasma lipids significantly predictive of incident T2D, independent of traditional risk factors. These findings highlight the importance of identifying novel lipid markers in early diabetes risk prediction.

Plasma Glucose Levels Increase During Spontaneous Attacks of Migraine With and Without Aura.

To investigate plasma glucose changes during the ictal state of migraine compared to the interictal state. Previous studies suggest abnormal glucose metabolism in migraine patients during and outside of attacks. It is not known if plasma glucose levels change during spontaneous migraine attacks. Plasma glucose levels were measured during and outside of spontaneous migraine attacks with and without aura. Plasma glucose values were corrected for diurnal variation of plasma glucose by subtracting the difference between the moving average (intervals of 2 hours) and overall mean from the plasma glucose values. This was a sub-study of a larger study conducted at Rigshospitalet Glostrup in the Capital Region of Denmark. Thirty-one patients (24 F, 7 M, 13 with aura, 18 without aura) were included in the study. Mean time from attack onset to blood sampling was 7.6hours. Mean pain at the time of investigation was 6 on a 0-10 verbal rating scale. Plasma glucose was higher ictally compared to the interictal phase (interictal mean: 88.63mg/dL, SD 11.70mg/dL; ictal mean: 98.83mg/dL, SD 13.16mg/dL, difference 10.20mg/dL, 95% CI=[4.30; 16.10]), P=.0014). The ictal increase was highest in patients investigated early during attacks and decreased linearly with time from onset of migraine (-1.57mg/dL/hour from onset of attack, P=.020). The attack-related increase in blood glucose was not affected by pain intensity or presence of aura symptoms. We demonstrated higher plasma glucose values during spontaneous migraine attacks, independent of the presence of aura symptoms and not related to pain intensity, peaking in the early phase of attacks. Additional studies are necessary to confirm our findings and explore the possible underlying mechanisms.

Icodextrin Versus Glucose Solutions for the Once-Daily Long Dwell in Peritoneal Dialysis: An Enriched Systematic Review and Meta-analysis of Randomized Controlled Trials

The efficacy and safety of icodextrin versus glucose-only peritoneal dialysis (PD) regimens is unclear. The aim of this study was to compare once-daily long-dwell icodextrin versus glucose among patients with kidney failure undergoing PD. Systematic review of randomized controlled trials (RCTs), enriched with unpublished data from investigator-initiated and industry-sponsored studies. Individuals with kidney failure receiving regular PD treatment enrolled in clinical trials of dialysate composition. Medline, Embase, CENTRAL, Ichushi Web, 10 Chinese databases, clinical trials registries, conference proceedings, and citation lists from inception to November 2018. Further data were obtained from principal investigators and industry clinical study reports. 2 independent reviewers selected studies and extracted data using a prespecified extraction instrument. Qualitative synthesis of demographics, measurement scales, and outcomes. Quantitative synthesis with Mantel-Haenszel risk ratios (RRs), Peto odds ratios (ORs), or (standardized) mean differences (MDs). Risk of bias of included studies at the outcome level was assessed using the Cochrane risk-of-bias tool for RCTs. 19 RCTs that enrolled 1,693 participants were meta-analyzed. Ultrafiltration was improved with icodextrin (medium-term MD, 208.92 [95% CI, 99.69-318.14] mL/24h; high certainty of evidence), reflected also by fewer episodes of fluid overload (RR, 0.43 [95% CI, 0.24-0.78]; high certainty). Icodextrin-containing PD probably decreased mortality risk compared to glucose-only PD (Peto OR, 0.49 [95% CI, 0.24-1.00]; moderate certainty). Despite evidence of lower peritoneal glucose absorption with icodextrin-containing PD (medium-term MD,-40.84 [95% CI,-48.09 to-33.59] g/long dwell; high certainty), this did not directly translate to changes in fasting plasma glucose (-0.50 [95% CI,-1.19 to 0.18] mmol/L; low certainty) and hemoglobin A1c levels (-0.14% [95% CI,-0.34% to 0.05%]; high certainty). Safety outcomes and residual kidney function were similar in both groups; health-related quality-of-life and pain scores were inconclusive. Trial quality was variable. The follow-up period was heterogeneous, with a paucity of assessments over the long term. Mortality results are based on just 32 events and were not corroborated using time-to-event analysis of individual patient data. Icodextrin for once-daily long-dwell PD has clinical benefit for some patients, including those not meeting ultrafiltration targets and at risk for fluid overload. Future research into patient-centered outcomes and cost-effectiveness associated with icodextrin is needed.

A novel non-PPARgamma insulin sensitizer: MLR-1023 clinicalproof-of-concept in type 2 diabetes mellitus

AimMLR-1023, called Tolimidone when evaluated unsuccessfully by Pfizer for gastric ulcer disease, has been repurposed as a novel oral insulin sensitizer with its effects mediated by selective activation of Lyn kinase. We aimed to evaluate the optimal dose, efficacy and safety of MLR-1023 in patients with type 2 diabetes. MethodsType 2 diabetes patients (18–75 years) on diet/exercise therapy were randomized and double-blinded to receive MLR-1023 (100-mg or 200-mg, once-daily [qd] or twice-daily [bid]) or matching placebo for 28 days. The primary endpoint was postprandial glucose (PPG) area under the curve (AUC0–3h) in a mixed meal tolerance test (MMTT) at day 29. Secondary endpoints included changes in fasting plasma glucose (FPG), insulin, HbA1c, lipids and body weight and adverse events. ANCOVA model was used for efficacy analysis. ResultsThe placebo-corrected least-squares mean differences (ΔLSM) in MMTT PPG AUC0-3 h (mmol/L) were −5.96 and −5.6 (both p = 0.03) in the MLR-1023 100-mg qd and 100-mg bid groups, respectively. The placebo-corrected ΔLSM in FPG (mmol/L) was −2.34 (p = 0.003) in the MLR-1023 100-mg qd group. Triglycerides improved with MLR-1023 (ΔLSM, −0.56 mmol/L, p = 0.07 and −0.59 mmol/L, p = 0.05) in the 200mgqd and 200 mg bid groups, respectively. Reductions in fasting insulin, HbA1c and body weight were not statistically significant. Most common adverse events with MLR-1023 treatment were headache (4.2%) and somnolence (2.5%). ConclusionsMLR-1023 100-mg once-daily for 4 weeks was the most effective dose with significant reduction in PPG AUC following a MMTT. MLR-1023 was safe and well-tolerated in patients with type 2 diabetes.Clinical Trials Registration Number: NCT02317796

Effect of High β-glucan Barley on Postprandial Blood Glucose and Insulin Levels in Type 2 Diabetic Patients

The aim of our study was to investigate whether high β-glucan-containing barley (7.2 g per 100 g) improves postprandial plasma glucose levels and suppresses postprandial insulin levels during a meal tolerance test in type 2 diabetic patients. A meal tolerance test (500 kcal) was conducted using two types of test meals: a test meal with white rice (WR) alone (WR diet) and a test meal with WR mixed with 50% barley (BR diet) as staple food. The side dish was the same in the both meals. The changes in plasma glucose and serum C-peptide immunoreactivity (CPR) levels for 180 minutes after ingestion of the test meals were compared. Ten patients with type 2 diabetes (age 52.5 ± 15.1 years, and 7 males and 3 females) were included in this study. The mean HbA1c level and body mass index were 8.8 ± 1.4%, and 29.7 ± 4.5 kg/m2, respectively. Plasma glucose levels after ingestion of the WR diet or BR diet peaked at 60 minutes, which showed no significant differences between the two types of test meals. However, the incremental area under the curve (IAUC) of plasma glucose levels after ingestion of BR diet was significantly lower than that of WR diet. The serum CPR levels at 180 min and their IAUC over 180 minutes after ingestion of BR diet were significantly lower than those of WR diet. Conclusion: Increase in postprandial plasma glucose and insulin levels was suppressed by mixing high-β-glucan barley with WR in type 2 diabetic patients.

Evaluation of type 2 diabetes treatment with gliclazide modified release in Azerbaijan (the EdiAzer study): Results from a 16-week observational clinical study

Introduction: Type 2 diabetes is a major public health problem across all economic regions. This open-label study collected real-world data on patients presenting with type 2 diabetes in Azerbaijan treated with gliclazide modified release (MR). Materials and Methods: Newly-diagnosed patients uncontrolled by diet, and patients uncontrolled by metformin were prescribed gliclazide MR 60mg (30–120mg/day) for 16 weeks. Primary study endpoints were changes in mean glycated hemoglobin A1c (HbA1c) and percentage of participants achieving HbA1c ≤7.0% and/or an HbA1c improvement ≥1.0%. Secondary endpoints included changes in mean fasting plasma glucose (FPG) and weight. Serious adverse events were monitored throughout the study. Results: Data from 105 patients were available for analysis. Mean age was 55.1 ± 10.4 years, 53.3% were female and 82.9% were overweight or obese. Mean duration of diabetes was 2.3 ± 2.6 years. A total of 44 patients were receiving metformin before study entry. At W0, 61 patients (58.1%) were prescribed gliclazide MR monotherapy, and 44 (41.9%) were prescribed gliclazide MR in combination with the metformin. At the end of the study, a statistically significant decrease was observed in mean HbA1c levels from 8.8% ± 1.4% to 7.6% ± 1.0% (P < 0.001). In addition, 30 (28.6%) patients achieved an HbA1c <7.0% (P < 0.0001), and 61 (58.1%) an HbA1c reduction of ≥1.0%. Reductions in FPG levels were statistically significant compared with baseline from week 2 onward. No weight gain was observed, and there were no serious adverse events, including no reports of severe hypoglycemia. Conclusion: Gliclazide MR is an effective and well-tolerated first- or second-line agent in type 2 diabetes and may be particularly valuable in low-to-middle income countries where therapeutic options are limited by accessibility and cost.

Efficacy of teneligliptin with metformin in Type 2 diabetes mellitus patients

Background: Type 2 diabetes mellitus (T2DM) is rapidly growing epidemic in India. It is well known that the level of glycemia is associated with complications of T2DM. Aims and Objectives: The objective of this study was to assess the efficacy of teneligliptin with metformin in T2DM patients. Materials and Methods: This was a randomized, open-label, comparative study carried out for the duration of 1 year in Gandhi Medical College, Secunderabad, Telangana. One hundred patients inadequately controlled on metformin 1 g alone; having glycated hemoglobin (HbA1c) >6.5, fasting blood sugar (FBS) >110 mg/dl, and postprandial blood sugar (PPBS) >180 mg/dl attending the outpatient Department of General Medicine, Kamineni Institute of Medical Sciences. All patients were randomly allotted into two groups. Fifty patients were started with teneligliptin along with metformin. Fifty patients were started with placebo while continuing with metformin. The endpoint was change in fasting plasma glucose (FPG), postprandial blood glucose (PPBH), and HbA1c levels at 24 weeks as compared to the baseline levels in both groups. The efficacy was assessed by measuring the change in the FPG, PPBH, and HbA1c levels after 24 weeks of treatment. Data were presented in the form of statistical tables and charts. SPSS software version 20 was used for statistical analysis. Results: After 24 weeks of treatment with teneligliptin and metformin, case subjects had significant decrease in FBS, PPBS, and HbA1c. There was no significant change in BMI, blood pressure, and lipid parameters in both groups after study. All patients tolerated drugs well without any side effects. Conclusions: The combination of teneligliptin with metformin was associated with clinically significant reduction in HbA1C. This study depicted that teneligliptin can be an effective alternative to other drugs for add on therapy to the patients who are inadequately controlled with metformin alone.

Hyperglycemia and FEP: Does Migration Status Matter?

Background: Several evidence have shown hyperglycemia and diabetes are frequent in patients with psychoses. There are evidences that some ethnic minorities are at higher risk of psychosis. It is less clear if migration history is a risk factor for diabetes and hyperglycemia during first-episode psychosis (FEP). The present study aims to evaluate if migration history might influence fasting plasma glucose change during antipsychotic treatment (APs) in (FEP). Materials and Methods: We carried out a retrospective follow-up of all FEP drug na?ve patients at their first contact with Bologna West Community Mental Health Centres from January 2010 to December 2015. Blood tests carried out during the follow-up period were collated from clinical charts to evaluate the baseline fasting plasma glucose level upon starting APs treatment and at the time of follow-up. Out of 50 patients who had FEP during the recruitment period and consented to take part in the study, 25 cases had blood test results available at follow-up. We performed linear multivariate regression analysis to adjust the association between migrant status and fasting plasma glucose level of follow-up by gender, age, education, employment, APs treatment and dose. Results: At baseline, the mean fasting plasma glucose level was within the normal range and at follow-up we observed a significant increase in the mean fasting plasma glucose in migrants. Upon multivariate linear regression analysis, migration history remained significantly associated with the follow-up fasting plasma glucose level. Conclusions: In conclusion, we found that migrants with FEP are particularly at risk of developing hyperglycemia and type II diabetes during APs treatment.

Efficacy and safety of insulin glargine 300 U/mL versus insulin glargine 100 U/mL in Asia Pacific insulin-naïve people with type 2 diabetes: The EDITION AP randomized controlled trial.

AimTo compare the efficacy and safety of Gla‐300 versus Gla‐100 in insulin‐naïve people with type 2 diabetes in Asia Pacific.Materials and MethodsIn this open‐label, randomized, active‐controlled, 26‐week study, insulin‐naïve participants with type 2 diabetes inadequately controlled with non‐insulin antihyperglycaemic drugs were randomized (2:1) to Gla‐300 or Gla‐100. The initial daily dose of basal insulin was 0.2 U/kg and was adjusted at least weekly for 8–12 weeks to a target fasting self‐monitored plasma glucose (SMPG) of 4.4–5.6 mmol/L.ResultsOf the 604 participants randomized, 570 (Gla‐300, n = 375; Gla‐100, n = 195) completed the study. Non‐inferiority of Gla‐300 versus Gla‐100 in HbA1c reduction from baseline to week 26 was confirmed. In the Gla‐300 and Gla‐100 groups, 51.1% and 52.2% of participants achieved the HbA1c target of <7.0% (rate ratio [95% CI]: 0.98 [0.84 to 1.14]) and 19.1% and 21.9% achieved the target without hypoglycaemia during the last 12 weeks of treatment (rate ratio [95% CI]: 0.87 [0.63 to 1.20]). Changes in fasting plasma glucose and 24‐hour average eight‐point SMPG were comparable between groups. Incidence of hypoglycaemia at any time of day was similar between treatment groups at week 26, but incidence of any nocturnal hypoglycaemia was numerically lower with Gla‐300 than Gla‐100 over the initial 12‐week titration period and 26‐week on‐treatment period. Rates of adverse events were similar between groups and low for serious adverse events.ConclusionsGlycaemic control of Gla‐300 is non‐inferior to Gla‐100 with a similar or lower incidence and proportion of hypoglycaemia in people with type 2 diabetes in Asia Pacific, reinforcing the results in the global EDITION programme.

Circulating PCSK9 levels are not associated with the conversion to type 2 diabetes

Background and aimsPCSK9 is an endogenous inhibitor of the LDL receptor pathway. Recently, Mendelian randomization studies have raised a doubt about the diabetogenic risk of PCSK9 inhibitors. Here, we assessed the relationship between plasma PCSK9 levels and the risk of new onset diabetes (NOD). MethodsFasting plasma PCSK9 levels were measured at baseline by ELISA in subjects without lipid lowering treatment in IT-DIAB (n = 233 patients with prediabetes, follow-up 5 years) and ELSA-Brasil (n = 1751; 27.5% with prediabetes, follow-up 4 years) prospective cohorts. The primary outcome in both studies was the incidence of NOD. The association of NOD with plasma PCSK9 levels was studied using multivariable Cox models. ResultsPlasma PCSK9 levels were not significantly associated with NOD in IT-DIAB (HR (+1SD) 0.96, CI95% [0.76; 1.21]) and ELSA-Brasil (OR (+1SD) 1.13 [0.89; 1.42]). In ELSA-Brasil, a significant positive association between PCSK9 and worsening of glucose homeostasis, including the progression from normoglycemia to prediabetes, was found (OR (+1SD) 1.17 [1.04; 1.30], p = 0.0074). Plasma PCSK9 concentration was also positively associated with the change in fasting plasma glucose between the first and second visit in ELSA-Brasil (β = 0.053, CI95% [0.006; 0.10], p = 0.026). Plasma PCSK9 levels positively correlated with total cholesterol in IT-DIAB and ELSA-Brasil, but not with glucose homeostasis parameters, except for a positive correlation with HOMA-IR in ELSA-Brasil. ConclusionsPlasma PCSK9 levels were not significantly associated with NOD risk in longitudinal analyses. These data suggest that inhibition of the PCSK9 extra-cellular pathway should not be deleterious for glucose homeostasis.

Long-Term Safety and Effectiveness of Linagliptin in Japanese Patients with Type 2 Diabetes Mellitus: A 3-Year Post-Marketing Surveillance Study.

IntroductionClinical trials of linagliptin in Japanese patients conducted to date have had limited observational periods; therefore, there is a need for additional longer-term real-world data. The aim of this study was to investigate the long-term safety and effectiveness of linagliptin in routine clinical practice.MethodsThis was a prospective, observational, post-marketing surveillance study conducted over 156 weeks in patients with type 2 diabetes mellitus who started linagliptin monotherapy. The primary endpoint was the incidence of adverse drug reactions (ADRs). The secondary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to last available observation. Other effectiveness endpoints included the change in HbA1c and change in fasting plasma glucose (FPG) from baseline to week 26 and over the course of the treatment period.ResultsOverall, 2235 and 2054 patients were included in the safety and effectiveness analysis sets, respectively. Patients were mostly male (58.4%), and the mean age was 66.7 years. The incidence of ADRs was 10.7% (n = 240). The most frequent ADRs according to MedDRA preferred terms were diabetes mellitus (n = 35 patients, 1.6%), constipation (n = 21, 0.9%), diabetes mellitus inadequate control (n = 13, 0.6%) and hypertension (n = 13, 0.6%). The mean change in HbA1c from baseline to last observation was − 0.67% [standard deviation (SD) 1.27%, 95% confidence interval − 0.72, − 0.61]. At week 26, HbA1c and FPG showed mean ± SD changes from baseline of – 0.73 ± 1.20% and − 21.02 ± 44.33 mg/dL, respectively, that were sustained until week 156.ConclusionsIn Japanese patients with type 2 diabetes mellitus, linagliptin produced sustained reductions in HbA1c and had a safety profile consistent with the established safety profile of linagliptin.Trial RegistrationClinicalTrials.gov (NCT01650259).Electronic supplementary materialThe online version of this article (10.1007/s13300-019-00723-x) contains supplementary material, which is available to authorized users.

Effects of Dexmedetomidine on Blood Glucose and Serum Potassium Levels in Children Undergoing General Anesthesia: A Secondary Analysis of Safety Endpoints During a Randomized Controlled Trial.

Dexmedetomidine is a highly selective α2-adrenergic agonist, which is increasingly used in pediatric anesthesia and intensive care. Potential adverse effects that have not been rigorously evaluated in children include its effects on blood glucose and serum potassium concentrations, which are relevant due to the associations of derangements of both parameters with undesired outcomes. We investigated the effects of 3 different doses of dexmedetomidine on these outcomes in a randomized controlled trial in children undergoing elective surgery. Sixty-four American Society of Anesthesiologists I-II children were randomized to receive either dexmedetomidine 0.25 µg/kg, dexmedetomidine 0.5 µg/kg, dexmedetomidine 0.75 µg/kg, or 0 µg/kg (control), as a bolus administered over 60 seconds after induction of anesthesia. Changes in plasma glucose and serum potassium concentrations were measured in venous blood sampled before and at 15 and 30 minutes after study drug administration. Data were plotted within and between groups and analyzed using a constrained longitudinal data approach. Forty-nine children completed the study. Mean glucose levels at 15 and 30 minutes were elevated with estimated changes from baseline of 0.37 mmol/L (95% CI, 0.29-0.45 mmol/L) and 0.05 mmol/L (95% CI, 0.00-0.10 mmol/L), respectively. At 15 minutes, there was a linear dose-response relationship (1.07 mmol/L/μg/kg [95% CI, 0.57-1.58 mmol/L/μg/kg]), but there was no appreciable effect of dexmedetomidine at 30 minutes (0.15 mmol/L/μg/kg [95% CI, -0.40 to 0.70 mmol/L/μg/kg]). Potassium levels were depressed relative to baseline, with a mean difference at 15 minutes of -0.20 mEq/L (95% CI, -0.28 to -0.12 mEq/L) and at 30 minutes of -0.12 mEq/L (95% CI, -0.15 to -0.08 mEq/L), but there was no appreciable effect of dexmedetomidine at either time. Small elevations in glucose and decreases in potassium were observed after induction of anesthesia in children. The elevation in glucose at 15 minutes depended on the dose of dexmedetomidine administered. These preliminary data warrant further investigation.

Telemonitoring and Team-Based Management of Glycemic Control on People with Type 2 Diabetes: a Cluster-Randomized Controlled Trial.

Connected devices that allow people with diabetes to monitor their blood glucose levels remotely with data visualization have been shown to improve self-care behavior in diabetes management. However, their effectiveness and usability for a low-middle-income, racially diverse population are unknown. This study aims to evaluate the effects of remote telemonitoring with team-based management on people with uncontrolled type 2 diabetes. This was a pragmatic 52-week cluster-randomized controlled study among 11 primary care government practices in Malaysia. People with type 2 diabetes aged 18 and above, who had hemoglobin A1c ≥ 7.5% but less than 11.0% within the past 3months and resided in the state of Selangor. The intervention group received home gluco-telemonitors and transmitted glucose data to a care team who could adjust therapy accordingly. The team also facilitated self-management by supporting participants to improve medication adherence, and encourage healthier lifestyle and use of resources to reduce risk factors. Usual care group received routine healthcare service. The primary outcome was the change in HbA1c at 24weeks and 52weeks. Secondary outcomes included change in fasting plasma glucose, blood pressure, lipid levels, health-related quality of life, and diabetes self-efficacy. A total of 240 participants were recruited in this study. The telemonitoring group reported larger improvements in glycemic control compared with control at the end of study (week 24, - 0.05%; 95% CI - 0.10 to 0.00%) and at follow-up (week 52, - 0.03%; - 0.07 to 0.02%, p = 0.226). Similarly, no differences in other secondary outcomes were observed, including the number of adverse events and health-related quality of life. This study indicates that there is limited benefit of replacing telemedicine with the current practice of self-monitoring of blood glucose. Further innovative methods to improve patient engagement in diabetes care are needed. ClinicalTrials.gov identifier: NCT02466880.

Effect of Empagliflozin on Free Fatty Acids and Ketone Bodies in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial.

We report a randomized, double-blind, placebo-controlled, 4-week study to investigate the effect of empagliflozin on free fatty acids and blood ketone bodies in Japanese patients with type 2 diabetes mellitus. Patients (baseline mean [standard deviation] glycated hemoglobin 7.91% [0.80%]; body mass index 24.3 [3.2] kg/m2) were randomized to empagliflozin 10mg (n = 20), empagliflozin 25mg (n = 19), or placebo (n = 21) daily as monotherapy for 28days. Meal tolerance tests (MTTs; breakfast, lunch, dinner) were performed on day - 1, day 1 (first day of treatment), and day 28. On day 1 and day 28, study drug was administered 1h before breakfast. Free fatty acids and blood ketone bodies were measured before and 1, 2, and 3h after each MTT, and the next morning (overnight fast). Empagliflozin significantly reduced plasma glucose and insulin and reduced body weight vs. placebo. Empagliflozin increased free fatty acids and total ketones bodies at day 1 and day 28. At day 28, the adjusted mean (95% confidence interval) difference vs. placebo in the time-corrected area under curve over 24h for total ketone bodies was 67.1 (12.3, 121.8) µmol·h/L·h (P = 0.017) with empagliflozin 10mg and 178.1 (123.9, 232.2) µmol·h/L·h (P < 0.001) with empagliflozin 25mg. Increases in ketones with empagliflozin vs. placebo peaked just before and declined after meals, with the highest peak before breakfast. Changes in total ketone bodies appeared to be associated with changes in plasma glucose, insulin, and free fatty acids. Empagliflozin modestly increased free fatty acids and blood ketone bodies after a single dose and 28days' treatment. Increases in ketones appeared to be related to the duration of fasting and were most pronounced before breakfast. Increases in ketones appeared to be associated with changes in well-known metabolic determinants of ketone production. ClinicalTrials.gov identifier, NCT01947855. Boehringer Ingelheim & Eli Lilly and Company.

Effects of high-protein diet on glycemic control, insulin resistance and blood pressure in type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

Obesity is a well-known risk factor of type 2 diabetes mellitus (T2DM), and it is commonly accompanied by T2DM. It is estimated that almost two thirds of the population with T2DM is also affected by hypertension. Elevated arterial blood pressure would increase the risk for diabetes development. Recently some studies indicated that a high-protein diet was effective for weight loss, and therefore we hypothesized that a high-protein diet could help control blood glucose, mitigate insulin resistance (IR) and improve blood pressure by weight management in T2DM patients. The study aimed to systematically review the effects of a high-protein diet on glycemic control, IR and blood pressure in T2DM patients. We searched four electronic databases until May 1st 2018 and included all randomized clinical trials comparing a high-protein diet with other diets. Two reviewers independently identified the trials for inclusion and independently extracted data. Either a fixed- or a random-effects model was used to combine the changes in each outcome from baseline to the end of the intervention. The meta-analysis was performed with RevMan 5.3 software. Twelve articles (thirteen studies) including 1138 T2DM patients met our inclusion criteria. Glycemic control was not significantly different between the high-protein diet and control group, with the changes in fasting plasma glucose (FPG) (-0.13 (95% CI (-0.46, 0.19), p=0.43) mmol/L) and HbA1c% (-0.05 (95% CI (-0.18, 0.08, p=0.92))) from baseline to the end of intervention. However, the difference in IR between the two groups was statistically significant. Most changes in lipids profiles were favorable. The changes in HDL, LDL, TC, and TG were+0.03 (95% CI (-0.04,0.11), p=0.35) mmol/L,-0.10 (95% CI (-0.18,-0.02), p=0.02) mmol/L,-0.21 (95% CI (-0.31,-0.12), p<0.01) mmol/L and-0.19 (95% CI (-0.33,-0.05), p<0.01) mmol/L, respectively. The result of HOMA-IR was-0.27 (95% CI (-0.47,-0.06), p<0.01). Additionally, the difference in blood pressure in terms of systolic blood pressure (-0.57 (95% CI (-2.45, 1.32), p=0.55)) and diastolic blood pressure (-0.73 (95% CI (-2.48, 1.02), p=0.41)) was not significant. This review showed that a high-protein diet does not significantly improve glycemic control and blood pressure, but can lower LDL, TC, TG and HOMA-IR levels in T2DM patients. Further studies are needed to clarify the effects of a high-protein diet on glycemic control, IR and blood pressure control in T2DM patients.