Differences In Fasting Plasma Glucose Research Articles

Effect of Switching from Low-Dose Simvastatin to High-Dose Atorvastatin on Glucose Homeostasis and Cognitive Function in Type 2 Diabetes.

BackgroundHigh-intensity statin is recommended in high-risk type 2 diabetes (T2D); however, statin dose dependently increases the risk of developing new-onset diabetes, can potentially worsen glycemic control in T2D, and may cause cognitive impairment. This study aimed to investigate the effect of statin intensification on glucose homeostasis and cognitive function in T2D.Materials and MethodsT2D patients who were taking simvastatin ≤20 mg/day were randomized to continue taking the same dosage of simvastatin (low-dose simvastatin group; LS, n=63) for 12 weeks, or to change to atorvastatin 40 mg/day for 6 weeks, and if tolerated, atorvastatin was increased to 80 mg/day for 6 weeks (high-dose atorvastatin group; HS, n=62). Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and of β-cell function (HOMA-B), cognitive functions using Montreal Cognitive Assessment (MoCA), and Trail Making Test (TMT) were assessed at baseline, 6 weeks, and 12 weeks.ResultsMean age of patients was 58.8±8.9 years, and 72% were female. Mean baseline FPG and HbA1c were 124.0±27.5 mg/dl and 6.9±0.8%, respectively. No differences in baseline characteristics between groups were observed. Change in HbA1c from baseline in the LS and HS groups was −0.1% and +0.1% (p=0.03) at 6 weeks, and −0.1% and +0.1% (p=0.07) at 12 weeks. There were no significant differences in FPG, fasting plasma insulin, HOMA-B, HOMA-IR, MoCA score, or TMT between groups at 6 or 12 weeks.ConclusionSwitching from low-dose simvastatin to high-dose atorvastatin in T2D resulted in a slight increase in HbA1c (0.1%) without causing cognitive decline.

Influence of Cinnamon on Glycemic Control in Individuals With Prediabetes: A Randomized Controlled Trial.

ContextThe identification of adjunct safe, durable, and cost-effective approaches to reduce the progression from prediabetes to type 2 diabetes (T2D) is a clinically relevant, unmet goal. It is unknown whether cinnamon’s glucose-lowering properties can be leveraged in individuals with prediabetes.ObjectiveThe objective of this work is to investigate the effects of cinnamon on measures of glucose homeostasis in prediabetes.Design, Setting, Participants, and InterventionThis double-blind, placebo-controlled, clinical trial randomly assigned adult individuals meeting any criteria for prediabetes to receive cinnamon 500 mg or placebo thrice daily (n = 27/group). Participants were enrolled and followed at 2 academic centers for 12 weeks.Main Outcome MeasuresPrimary outcome was the between-group difference in fasting plasma glucose (FPG) at 12 weeks from baseline. Secondary end points included the change in 2-hour PG of the oral glucose tolerance test (OGTT), and the change in the PG area under the curve (AUC) derived from the OGTT.ResultsFrom a similar baseline, FPG rose after 12 weeks with placebo but remained stable with cinnamon, leading to a mean between-group difference of 5 mg/dL (P < .05). When compared to the respective baseline, cinnamon, but not placebo, resulted in a significant decrease of the AUC PG (P < .001) and of the 2-hour PG of the OGTT (P < .05). There were no serious adverse events in either study group.ConclusionsIn individuals with prediabetes, 12 weeks of cinnamon supplementation improved FPG and glucose tolerance, with a favorable safety profile. Longer and larger studies should address cinnamon’s effects on the rate of progression from prediabetes to T2D.

The effect of coffee consumption on insulin sensitivity and other biological risk factors for type 2 diabetes: a randomized placebo-controlled trial

In observational studies, coffee consumption has been consistently associated with a lower risk of type 2 diabetes mellitus. Trials examining the effect of coffee consumption on glucose metabolism have been limited by the use of surrogate insulin sensitivity indices, small sample sizes, lack of blinding, and short follow-up duration. We aimed to overcome limitations of previously conducted coffee trials in a randomized placebo-controlled trial of the effect of coffee consumption on insulin sensitivity. We conducted a 24-wk randomized placebo-controlled trial in 126 overweight, non-insulin sensitive (HOMA-IR≥1.30), Chinese, Malay, and Asian-Indian males and females aged 35-69 y. Participants were randomly assigned to receive 4 cups of instant regular coffee (n=62) or 4 cups of a coffee-like placebo beverage (n =64) per day. The primary outcome was the amount of glucose metabolized per kilogram of body weight per minute (Mbw) assessed during steady-state conditions with a hyperinsulinemic euglycemic clamp. Secondary outcomes included other clamp-based insulin sensitivity measures, biological mediators of insulin sensitivity, and measures of fasting glucose metabolism. Coffee consumption did not significantly change insulin sensitivity compared with placebo (percentage mean difference in Mbw = 4.0%; 95% CI: -8.3, 18.0%; P=0.53). Furthermore, no significant differences in fasting plasma glucose (2.9%; 95% CI: -0.4, 6.3%; P=0.09) or biological mediators of insulin resistance, such as plasma adiponectin (2.3%; 95% CI: -1.4, 6.2%; P=0.22), were observed between coffee and placebo groups over 24 wk of intervention. Participants in the coffee arm experienced a loss of fat mass (FM) (-3.7%; 95% CI: -6.3, -1.1%; P=0.006) and reduction in urinary creatinine concentrations (-21.2%; 95% CI: -31.4, -9.5%; P=0.001) compared with participants in the placebo arm over 24 wk of intervention. Consuming 4 cups/d of caffeinated coffee for 24 wk had no significant effect on insulin sensitivity or biological mediatorsof insulin resistance but was associated with a modest lossofFM and reduction in urinary creatinine concentrations.Thistrial was registered at clinicaltrials.gov as NCT01738399. Registered on November 28, 2012. Trial sponsor: Nestlé Research, Lausanne, Switzerland. Trial site: National University of Singapore.

Impact of Fecal Microbiota Transplantation on Obesity and Metabolic Syndrome—A Systematic Review

Fecal microbiota transplantation (FMT) is a gut microbial-modulation strategy that has been investigated for the treatment of a variety of human diseases, including obesity-associated metabolic disorders. This study appraises current literature and provides an overview of the effectiveness and limitations of FMT as a potential therapeutic strategy for obesity and metabolic syndrome (MS). Five electronic databases and two gray literature sources were searched up to 10 December 2018. All interventional and observational studies that contained information on the relevant population (adult patients with obesity and MS), intervention (receiving allogeneic FMT) and outcomes (metabolic parameters) were eligible. From 1096 unique citations, three randomized placebo-controlled studies (76 patients with obesity and MS, body mass index = 34.8 ± 4.1 kg/m2, fasting plasma glucose = 5.8 ± 0.7 mmol/L) were included for review. Studies reported mixed results with regards to improvement in metabolic parameters. Two studies reported improved peripheral insulin sensitivity (rate of glucose disappearance, RD) at 6 weeks in patients receiving donor FMT versus patients receiving the placebo control. In addition, one study observed lower HbA1c levels in FMT patients at 6 weeks. No differences in fasting plasma glucose, hepatic insulin sensitivity, body mass index (BMI), or cholesterol markers were observed between two groups across all included studies. While promising, the influence of FMT on long-term clinical endpoints needs to be further explored. Future studies are also required to better understand the mechanisms through which changes in gut microbial ecology and engraftment of microbiota affect metabolic outcomes for patients with obesity and MS. In addition, further research is needed to better define the optimal fecal microbial preparation, dosing, and method of delivery.

Efficacy and safety of sitagliptin added to metformin and insulin compared with voglibose in patients with newly diagnosed type 2 diabetes

OBJECTIVE:To assess the efficacy and safety of sitagliptin compared with voglibose added to combined metformin and insulin in patients with newly diagnosed type 2 diabetes (T2DM).METHODS:In this 12-week prospective, randomized, parallel trial, 70 newly diagnosed T2DM patients with glycosylated hemoglobin (HbA1c) ≥9% and/or fasting plasma glucose (FPG) ≥11.1 mmol/L were randomized (1:1) to receive sitagliptin 100 mg per day + metformin + insulin glargine or voglibose 0.2 mg three times daily + metformin + insulin glargine. Change in HbA1c at week 12 was the primary endpoint.RESULTS:The mean baseline HbA1c was 11.0% in the patients. The changes in HbA1c from baseline were -6.00% in the sitagliptin group and -3.58% in the voglibose group, and the between-group difference was -2.42% (95% CI -1.91 to -2.93, p=0.02). The differences in FPG and homeostatic model assessment of β-cell function (HOMA-β) and the change in body weight between groups from baseline were -2.95 mmol/L (p=0.04), 43.91 (p=0.01) and -2.23 kg (p=0.01), respectively. One patient (2.9%) in the sitagliptin group and three patients (8.6%) in the voglibose group exhibited hypoglycemia.CONCLUSIONS:Sitagliptin added to combined metformin and insulin therapy showed greater efficacy and good safety regarding hypoglycemia in patients with newly diagnosed T2DM compared with voglibose.

Role of glucose transporter 2 and 4 in insulin resistance in spontaneous hyperuricemia mice

Objective To investigate the role of glucose transporter (GLUT) 2 and 4 in hyperuricemia-induced insulin resistance. Methods Male uric acid oxidase gene knock-out spontaneous hyperuricemia mice (KO) and wild-type mice (WT) were fed with high-fat diet to establish an insulin resistance model. Then, some of KO mice were treated with allopurinol for lowering uric acid. Uric acid, fasting plasma glucose (FPG), and fasting insulin (FINS) were detected. Intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed. Finally, the expression levels of Slc2a4 and Slc2a2 mRNA in tissues were determined by real-time PCR, while those of GLUT2 and GLUT4 proteins in tissues were analyzed by Western blot. Results There was no significant difference in FPG among various groups. The level of FINS in KO group was significantly higher than that in WT group [(0.636±0.07) vs (0.456±0.03) ng/ml, P<0.01], with decreased insulin sensitivity and impaired glucose tolerance. The uric acid level in the KO group remained at a high level [(549.68±48.7) vs (216.61±27.5)μmol/L]. After uric acid level in KO mice was reduced by allopurinol, insulin sensitivity and glucose metabolism were improved. Compared with WT group, the expression levels of Slc2a4 and GLUT4 in the gastrocnemius muscle were decreased while the expression levels of Slc2a2 and GLTU2 in liver were increased in KO group, which were reversed by allopurinol-mediated uric acid reduction. Conclusion Uric acid may induce insulin resistance via decreasing Slc2a4/GLUT4 expressions in skeletal muscle, and increasing Slc2a2/GLTU2 expressions in liver. (Chin J Endocrinol Metab, 2018, 34: 862-866) Key words: Hyperuricemia; Insulin resistance; Glucose transporter 2; Glucose transporter 4

Effectiveness of Second-Line Agents in the Treatment of Uncomplicated Type 2 Diabetes Mellitus: An Observational Tertiary-Care Based Study

Background: The rational prescribing of second-line drugs in type 2 diabetes mellitus (DM) require clear guidelines. There is no sufficient empirical evidence to support the use of one second-line agent over the other and when to initiate second-line drug is still under discrepancy. Objectives: To analyze the utilization pattern and effectiveness of second-line agents in uncomplicated type 2 DM. Methodology: 240 uncomplicated type 2 DM patients who were ≥ 18 years receiving either metformin/sulfonylurea or metformin+sulfonylurea was divided into four add-on treatment group 1, 2, 3, 4; that were added pioglitazone, dipeptidyl peptidase-4(DPP-4) inhibitor, voglibose, and insulin [pre-mixed insulin (30%regular/70%NPH)] respectively and received the second-line agents for a duration of 6 months or longer. Effectiveness was based on the reduction in glycosylated hemoglobin (HbA1C), fasting plasma glucose (FPG) and postprandial blood glucose (PPBG) values over 3 and 6 months was done using repeated measures analysis of variance (ANOVA). Results: The mean difference for reduction in HbA1C (%) values at 3rd and 6th month with respect to baseline values was 1.32±0.72 and 2.11±0.97; 1.19±0.27 and 1.81±0.53; 1.16±0.41 and 1.66±0.63; 0.97±0.16 and 1.46±0.47 for pioglitazone, DPP-4 inhibitor, voglibose, insulin respectively. The mean difference in FPG and PPBG levels at the 6th month from baseline was 75±31.06 and 115.3±40.32; 77.91±37.95 and 117±41.27; 85.87±21.75 and 118.75±55.86; 91.38±31.8 and 132.03±56.24 for pioglitazone, DPP-4 inhibitors, voglibose and insulin respectively. Reduction in HbA1C, FPG, and PPBG was statistically significant within each group at each time interval with p-value Key words: Anti-diabetic drugs, FPG, HbA1C, PPBG, Second-line agents.

The correlation between serum adipokines levels and metabolic indicators in girls with Turner syndrome

ObjectiveThe following study investigated the serum adiponectin, chemerin and vaspin levels and their relationship with body mass index (BMI), glucose and lipid metabolism in girls with Turner Syndrome (TS). MethodsA total of 64 girls with TS (mean age, 12.22 ± 3.98 years; mean BMI, 18.90 ± 3.45 kg/m2) were ascertained by chromosome analysis. Height, weight, waist circumference, hip circumference and blood pressure were measured, as well as the levels of fasting plasma glucose (FPG), fasting plasma insulin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG). The BMI, BMI standard deviation score (SDS), waist to hip ratio, waist to height ratio and insulin resistance index (HOMA-IR) were calculated. The TS group and the control group were subdivided into non-puberty or puberty subgroup. ResultsThe TS group had higher waist to hip ratio and waist to height ratio compared to the control group. There was no significant difference in FPG, fasting plasma insulin, HOMA-IR, blood lipid and blood pressure between the two groups. Significantly higher serum levels of adioponectin (12.51 ± 4.58 μg/ml) and chemerin (173.71 ± 37.88 ng/ml) and significantly lower levels of vaspin (0.67 ± 0.47 ng/ml) were found in the TS group compared to the control group (9.30 ± 3.17 μg/ml, 159.43 ± 23.19 ng/ml and 1.06 ± 0.49 ng/ml, respectively) (all P < 0.05). In the TS group, adiponectin levels were negatively correlated with age, BMI and TG (r = −0.251, −0.247, −0.294, P < 0.05 for all). In the control group, adiponectin levels were negatively correlated with BMI and BMI SDS (r = −0.416 and −0.315, P < 0.05 for both), while vaspin levels were positively correlated with age, fasting plasma insulin and HOMA-IR (r = 0.257, 0.273 and 0.282, P < 0.05 for all). In addition, significantly higher levels of adiponectin were found in the non-puberty subgroup (13.88 ± 4.49) μg/ml compared to puberty subgroup (9.72 ± 3.39) μg/ml (P < 0.05), while no significant differences in chemerin and vaspin were found between the two TS subgroups. ConclusionsElevated adiponectin and chemerin levels and significantly reduced vaspin were found in girls with TS. Puberty or estrogen replacement therapy may reduce adiponectin in girls with TS.

Abstract 040: The Effects of Coffee Consumption on Insulin Sensitivity and Other Risk Factors for Type 2 Diabetes

Background: In observational studies, coffee consumption has been consistently associated with a lower risk of type 2 diabetes mellitus. Trials examining the effect of coffee consumption on glucose metabolism have been limited by the use of surrogate insulin sensitivity indices, small sample sizes, lack of blinding, and short follow-up duration. We aimed to overcome these limitations in a randomized placebo-controlled trial examining the effects of coffee consumption on insulin sensitivity. Methodology: We conducted a 24-week randomized placebo-controlled trial in 126 overweight, insulin-resistant (HOMA-IR ≥ 1.30), Chinese, Malay and Asian-Indian males and females aged 35-69 years. Participants were randomly assigned to receive 4 cups of instant regular coffee (n=62) or 4 cups of a coffee-like placebo beverage (n=64) per day. The primary outcome was bodyweight-standardized M-value (M bw ) assessed with a hyperinsulinemic euglycemic clamp. Secondary outcomes included other clamp-based insulin sensitivity measures, biological mediators of insulin sensitivity, and measures of fasting glucose metabolism, body weight and composition. Results: Coffee consumption did not significantly change insulin sensitivity as compared with placebo [% mean difference in M bw : 0.3% (95% CI: -12.0% to 14.2%), P =0.97]. Furthermore, no significant differences in fasting plasma glucose [3.0% (-1.1% to 7.3%), P =0.16] or biological mediators of insulin resistance, such as plasma adiponectin [1.5% (-3.4% to 6.6%), P =0.55], were observed between coffee and placebo groups after 24 weeks of intervention. Coffee consumption led to a loss of body weight as compared with placebo [-1.2% (-2.3% to -0.1%), P =0.03] resulting from a decrease in fat mass [-3.7% (-7.1% to -0.2%), P =0.04] . Conclusions: Consuming 4 cups per day of caffeinated coffee for 24 weeks had no significant effect on insulin sensitivity or biological mediators of insulin resistance. Coffee consumption led to a modest decrease in body fat as compared with coffee abstinence. Trial Registration: ClinicalTrials.gov identifier: NCT01738399. Registered on 28 November 2012. Trial Sponsor: Nestlé Research Center, Lausanne, Switzerland. Trial Site: National University of Singapore.

Clinical perspectives from the BEGIN and EDITION programmes: Trial-level meta-analyses outcomes with either degludec or glargine 300 U/mL vs glargine 100 U/mL in T2DM

AimsTo explore comparative glycaemic control and hypoglycaemia incidence with insulin degludec 100U/mL (IDeg) or insulin glargine 300U/mL (Gla-300) versus glargine 100U/mL (Gla-100) in trial-level meta-analyses of phase 3a clinical trials including people with type-2 diabetes. MethodsMeta-analyses of HbA1c, fasting plasma glucose (FPG), average 24h self-measured plasma glucose (SMPG), pre-breakfast SMPG and hypoglycaemia incidence and rate, using data from the BEGIN (IDeg) and EDITION (Gla-300) insulin development programmes, were performed. ResultsIn BEGIN, despite greater FPG reduction with IDeg than Gla-100, HbA1c reduction was greater with Gla-100 (mean difference [95% CI] in HbA1c change: 0.09 [0.01–0.18] %) whereas in EDITION, there was no difference in FPG and HbA1c reduction between Gla-300 and Gla-100. Risk of nocturnal confirmed (<3.1mmol/L [<56mg/dL]) or severe hypoglycaemia, but not anytime (24h) events, was lower with IDeg than Gla-100 (relative risk [RR] 0.79 [0.66–0.94]) whereas Gla-300 was associated with reduced risk of nocturnal (RR 0.75 [0.61–0.92]) and anytime (24h) (RR 0.81 [0.69–0.94]) confirmed (<3.0mmol/L [<54mg/dL]) or severe hypoglycaemia versus Gla-100. ConclusionsThese trial-level meta-analyses suggest that despite greater reductions in FPG, IDeg was associated with less improvement in HbA1c versus Gla-100, with a hypoglycaemia benefit only evident at night. In contrast, Gla-300 showed similar HbA1c reduction to Gla-100, accompanied by lower risk of hypoglycaemia both at night and at any time of day. Gla-300 and IDeg appear more similar than dissimilar, but head-to-head trials are required.

Individualized homeopathic treatment in addition to conventional treatment in type II diabetic patients in Hong Kong – a retrospective cohort study

Objective: Glycaemic goals are not achieved in most patients with type II diabetes mellitus (T2DM), especially in those with long disease duration and taking multiple oral antidiabetic drugs (OAD). We aimed to investigate the effectiveness of individualized homeopathic treatment in glycaemic control. Design: Retrospective cohort study. Setting: At least 6 months of individualized homeopathic treatment at a private homeopathic centre in Hong Kong. Participants: Twenty-seven adults aged 37–84 years were treated with individualized homeopathic remedies between 2012 and 2015. Published data on 40 T2DM patients under standard conventional treatment in Hong Kong were used as a control. Main outcome measure: Change in fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) at 12-month or the last follow-up, whichever is earlier. Results: Compared with the conventional treatment only group, the homeopathy group had higher baseline FPG ( p = 0.044), and more patients had a long (>20 years) duration of diabetes ( p = 0.006), and a history of cardiac events ( p = 0.022). The mean difference in FPG in the homeopathy group was significantly greater than in the control after 12 months: −2.24 mmol/L (95% confidence interval [CI]: −3.47 to −1.01) vs 0.16 mmol/L (95% CI: −1.72 to 2.04), p = 0.001. The mean difference in glycated haemoglobin (HbA1c) was also significantly greater, −1.11% (95% CI: −2.17 to −0.05) vs 0.08% (95% CI: −1.37 to 1.53), p = 0.046. Poorer baseline glycaemic control was associated with better outcome (r = −0.750, p < 0.001), but not the duration of diabetes (r = 0.058, p = 0.772). The improvement was robust to sensitivity analyses. Conclusion: Individualized homeopathic treatment was associated with better glycaemic control compared with standard conventional treatment alone.

Gender difference in type 2 diabetes and the role of body iron stores.

Background Studies of gender difference in type 2 diabetes have been inconclusive. We investigated gender difference in type 2 diabetes and the contribution of body iron, as assessed by serum ferritin to this difference. Methods We performed cross-sectional ( n = 1707) and prospective ( n = 1506) analyses in males and females aged 53-73 years in 1998-2001. Type 2 diabetes diagnosis was determined by questionnaire, blood glucose measurements and record linkage to type 2 diabetes registers. Gender difference in type 2 diabetes and serum ferritin contribution to the difference was examined in multivariable logistic and Cox regression models. Gender difference in fasting plasma glucose and insulin and homeostasis model assessment of insulin resistance was examined in linear regression analysis. Results In the cross-sectional analysis, a total of 201 type 2 diabetes cases were observed (males = 111 [55.2%] vs. female = 90 [44.8%], P = 0.032), and in adjusted models, males had higher odds of type 2 diabetes (OR = 1.61, 95% CI 1.10 to 2.34); higher fasting plasma glucose (β = 0.28, 95% CI 0.15 to 0.41), fasting plasma insulin (β = 0.73, 95% CI 0.26 to 1.19) and homeostasis model assessment of insulin resistance (β = 0.11, 95% CI 0.04 to 0.17). In the prospective analysis, males had increased risk of type 2 diabetes (HR = 1.46, 95% CI 1.03 to 2.07). With serum ferritin introduction (100 µg/L, log-transformed) into the models, the type 2 diabetes prevalence (OR = 1.35, 95% CI 0.91 to 1.99) and incidence (HR = 1.38, 95% CI 0.96 to 1.97) were appreciably attenuated. Conclusions These data suggest a gender difference in type 2 diabetes, with a higher prevalence and increased type 2 diabetes risk in males. Body iron explains about two-fifths and one-fifth of the gender difference in type 2 diabetes prevalence and incidence, respectively.

Effect of daily calcitriol supplementation with and without calcium on disease regression in non-alcoholic fatty liver patients following an energy-restricted diet: Randomized, controlled, double-blind trial

Despite evidence for beneficial effects of vitamin D, to our knowledge, no study has compared the effects of calcium supplementation with vitamin D on non-alcoholic fatty liver disease (NAFLD) regression during a hypo-energetic program. We compared the effect of the vitamin D supplementation with and without calcium on anthropometric measures and biochemical parameters in NAFLD patients during a weight-loss program. A 12-week, randomized, controlled, double-blind trial was conducted in 120 NAFLD patients randomly assigned to receive 25μg calcitriol (n=37), 500mg calcium carbonate+25μg calcitriol (n=37), or placebo (n=36) every day with their lunch meals while following a weight-loss program. Weight, BMI and fat mass reduction were significant in each group after 12wk of intervention (p<0.001), but differences among the groups was not significant after 12wk of the study, adjusted to the baseline measurements. Significant reduction in fasting plasma glucose (FPG), insulin, insulin resistance (by HOMA-IR) and TG concentrations and an increase in HDL.C was seen over the 12wk of study in each group (p<0.001). Adjusting to the baseline measurements, there was significant difference in FPG (p<0.001), HOMA-IR (p<0.001), serum insulin (p=0.01), TG (p=0.01) and HDL.C (p<0.001) among the groups after 12wk of the study. The calcium plus calcitriol group showed a significant decrease in ALT and FPG and increase in HDL.C level compared with the calcitriol group, adjusted to the baseline measures (p<0.001). Our results suggest that calcium plus calcitriol supplementation for 12 weeks may be potentially effective for biochemical parameters in NAFLD patients. Further additional larger controlled trials are needed to confirm these findings. Registered under ClinicalTrials.gov Identifier no. IRCT201408312709N29.

Insulin degludec in a simple or stepwise titration algorithm in a Japanese population of patients with type 2 diabetes: a randomized, 26-week, treat-to-target trial.

Managing insulin therapy is a challenge for both patients and healthcare providers.The primary aim of this trial was to compare the efficacy and safety of insulin degludec (IDeg) in a fixed versus flexible dosing schedule. The secondary aim and subject of this manuscript was to compare a simple versus a stepwise titration algorithm. This was a 26-week, controlled, multicenter, open-label, randomized, treat-to-target phase 3b trial of Japanese patients with type 2 diabetes inadequately treated with insulin glargine and with/without antidiabetic drugs orally. The trial had a 2×2 factorial design whereby 458 patients were randomized 1:1:1:1 to one of two titration algorithms and one of two dosing schedules. IDeg dose was adjusted weekly using a clinician-led, treat-to-target approach in order to ensure optimal insulin titration and glycemic control following self-measured blood glucose (SMBG) readings. Mean insulin dose at the end of the trial was similar in both simple and stepwise titration algorithms. Glycemic control improved in both titration algorithms, with noninferiority in glycated hemoglobin (HbA1c) reduction confirmed when comparing simple and stepwise titration algorithms and no significant differences in fasting plasma glucose or SMBG at 26weeks. No safety concerns were observed in terms of adverse events, and rates of hypoglycemia were not significantly different between the two algorithms. This trial demonstrated comparable efficacy with noninferior HbA1c and comparable safety of once-daily IDeg using either a simple or stepwise titration algorithm in Japanese patients with type 2 diabetes inadequately controlled with insulin glargine.

Effect of Vitamin D3 Supplementation on Inflammatory Markers and Glycemic Measures among Overweight or Obese Adults: A Systematic Review of Randomized Controlled Trials.

BackgroundObesity induced low-grade chronic inflammation disrupts proper immune and metabolic function. Vitamin D deficiency increases inflammation, which is associated with cardiometabolic risk. This systematic review examines the association between oral vitamin D (VD) supplementation and circulating inflammatory biomarkers and glycemic outcomes from randomized controlled trials (RCTs) of overweight and/or obese adults.MethodsMEDLINE OVID, EMBASE and the Cochrane Central Register of Controlled Trials were searched according to a predefined protocol. Eligible RCTs included adults randomized to receive either oral VD or placebo. Two reviewers independently assessed RCTs for inclusion. Bias was assessed using the Cochrane Collaboration risk of bias tool. Mean differences were calculated comparing end-of-study sample means between the independent VD and placebo groups.ResultsEleven unique RCTs met inclusion criteria from a total of 3,383 identified citations, including 79 screened articles and 14 full text data extractions. Inflammatory and glycemic measures were reported in 7 and 10 RCTs, respectively. Most trial findings were non-significant with considerable heterogeneity in design, participants and outcomes. All but one trial was rated as either high or unclear risk of bias. Two RCTs reported significant changes in inflammatory biomarkers; however, the mean difference between groups was not statistically significant: C-reactive protein 0.19 mg/L (p = 0.88); Tumor Necrosis Factor -0.54 pg/ml (p = 0.20). Two other trials found significant mean differences in fasting plasma glucose -0.32 mmol/L (p = 0.03), Hemoglobin A1c -0.13% (p = 0.04), and Homeostatic Model Assessment -0.86 (p = 0.02) following VD supplementation.ConclusionsOverall, there is no clear established benefit of VD supplementation on inflammatory biomarkers among overweight/obese adults. Baseline serum VD possibly influences the effect of VD repletion on inflammatory markers. Risk of bias was present in most studies, thus supporting the need for higher quality studies in this area to more conclusively understand the role VD supplementation has on inflammatory pathways.

Vildagliptin as add-on therapy to insulin improves glycemic control without increasing risk of hypoglycemia in Asian, predominantly Chinese, patients with type 2 diabetes mellitus.

The aim of the present study was to investigate the efficacy and safety of vildagliptin added onto insulin with or without metformin in an Asian, predominantly Chinese, population with type 2 diabetes mellitus (T2DM). In this 24-week, multicenter, double-blind, placebo-controlled trial, patients with T2DM inadequately controlled (HbA1c 7.5%-11.0%) on stable therapy with long-acting, intermediate-acting, or premixed insulin, with or without concomitant metformin, were randomized to receive vildagliptin 50 mg b.i.d. or placebo. Of 293 patients randomized, 146 received vildagliptin and 147 received placebo treatment. At baseline, the overall mean age of patients was 58.1 years, mean T2DM duration was 11.3 years, and mean HbA1c was 8.7%. The adjusted mean (±SE) change in HbA1c at Week 24 in the vildagliptin and placebo groups was -1.08 ± 0.12% and -0.38 ± 0.12%, respectively (between-treatment difference -0.70 ± 0.16%; P < 0.001). The between-group difference in fasting plasma glucose was -0.43 ± 0.38 mmol/L (P = 0.259). Significantly, more patients achieved HbA1c <7.0% with vildagliptin than with placebo (23.6% vs. 11.2%; P = 0.006). The incidence of adverse events in the vildagliptin and placebo groups was 43.8% and 46.3%, whereas that of serious adverse events was 3.4% and 6.8%, respectively. The frequency of hypoglycemia was lower in the vildagliptin than placebo group (2.7% vs. 5.4%). The addition of vildagliptin 50 mg b.i.d. significantly improved glycemic control without an increased risk of hypoglycemia in Asian, predominantly Chinese, patients with T2DM inadequately controlled on insulin, with or without metformin.

Identification of cysteinylated transthyretin, a predictive biomarker of treatment response to partially hydrolyzed guar gum in type 2 diabetes rats, by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.

Recent evidence has indicated that total fiber intake is inversely related to type 2 diabetes risk. The present study aimed to investigate the effects of chronic administration of partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber, on the occurrence of diabetes and its complications, fatty liver and nephropathy. We also identified predictive serum biomarkers of treatment response to PHGG by mass spectroscopy-based proteomic analysis using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a good model of human non-insulin-dependent diabetes mellitus. In this study, at 5 weeks of age, OLETF rats and control strain Long-Evans Tokushima Otsuka (LETO) rats were fed a control diet or a high-fiber diet (5% PHGG) for 57 weeks. Body weight, food intake, oral glucose tolerance test, plasma insulin levels, and urine glucose and protein levels were regularly measured. Oral glucose tolerance tests (OGTT) and storage of serum in a deep freezer were conducted at the beginning of the experiment and every 4 weeks after overnight fasting during the experiments. PHGG treatment affected neither meal patterns nor the body weight of OLETF and LETO rats. Repeated measure analysis of variance revealed significant differences in fasting plasma glucose and plasma glucose at 2 h after OGTT between control OLETF (OLETF-C) rats and OLETF rats treated with PHGG (OLETF-F). The glucose response determined by the area under the curve of OGTT was significantly greater in OLETF-C rats than that in OLETF-F rats at 25 weeks of age. HOMA-IR, an index of insulin resistance, increased at 25 weeks of age in OLETF-C rats, while this increase was significantly inhibited in OLETF-F rats. At 62 weeks of age, PHGG treatment significantly improved hepatic steatosis as well as renal mesangial matrix accumulation in OLETF rats. To identify the risk marker for diabetes mellitus by SELDI-TOF MS, we collected sera from 21-week-old individuals. Among the 12 specific peaks that were risk marker candidates for diabetes mellitus, the m/z 13,720 peak was identified as that of cysteinylated transthyretin by sequencing of four tryptic peptides using tandem mass spectrometry and peak distribution around the m/z 13,720 peak in the SELDI-TOF spectra. In conclusion, we found that chronic treatment with PHGG improved insulin resistance, delayed the onset of diabetes, and inhibited the development of diabetic complications, as well as identified cysteinylated transthyretin as a predictive biomarker of treatment response to PHGG in OLETF rats.

Obese Patients With a Binge Eating Disorder Have an Unfavorable Metabolic and Inflammatory Profile.

To evaluate whether obese patients with a binge eating disorder (BED) have an altered metabolic and inflammatory profile related to their eating behaviors compared with non-BED obese.A total of 115 White obese patients consecutively recruited underwent biochemical, anthropometrical evaluation, and a 75-g oral glucose tolerance test. Patients answered the Binge Eating Scale and were interviewed by a psychiatrist. The patients were subsequently divided into 2 groups according to diagnosis: non-BED obese (n = 85) and BED obese (n = 30). Structural equation modeling analysis was performed to elucidate the relation between eating behaviors and metabolic and inflammatory profile.BED obese exhibited significantly higher percentages of altered eating behaviors, body mass index (P < 0.001), waist circumference (P < 0.01), fat mass (P < 0.001), and a lower lean mass (P < 0.001) when compared with non-BED obese. Binge eating disorder obese also had a worse metabolic and inflammatory profile, exhibiting significantly lower high-density lipoprotein cholesterol levels (P < 0.05), and higher levels of glycated hemoglobin (P < 0.01), uric acid (P < 0.05), erythrocyte sedimentation rate (P < 0.001), high-sensitive C-reactive protein (P < 0.01), and white blood cell counts (P < 0.01). Higher fasting insulin (P < 0.01) and higher insulin resistance (P < 0.01), assessed by homeostasis model assessment index and visceral adiposity index (P < 0.001), were observed among BED obese. All differences remained significant after adjusting for body mass index. No significant differences in fasting plasma glucose or 2-hour postchallenge plasma glucose were found. Structural equation modeling analysis confirmed the relation between the altered eating behaviors of BED and the metabolic and inflammatory profile.Binge eating disorder obese exhibited an unfavorable metabolic and inflammatory profile, which is related to their characteristic eating habits.

Abstract 15980: Effects of a Concurrent Strength and Endurance Training Program in Diabetes Patients a Randomized Controlled Trial

Background: The prevalence of diabetes have increased globally to epidemic proportions; glycemic control and treatment remains a challenge. Concurrent aerobic and resistance training programs (CART) have been widely recommended as an important strategy to improve physiologic and functional performance. Objective: The impact of CART programs on metabolic profile, glycemic control and exercise capacity status in patients with diabetes requires additional study, which is the primary aim of the current study. Materials and Methods: We evaluated 41 patients (15 female and 19 male, 50.8±7 years) with a confirmed diagnosis of diabetes. The subjects were randomized in two groups: sedentary group (SG) and CART group (CART-G). CART was performed 12 weeks, 3 times a week for approximately 1 hour per session (30 minutes aerobic and 30 minutes resistance). Body habitus was assessed by body mass index, waist circumference, and skinfolds. Peripheral muscular strength was evaluated by an isokinetic dynamometer and pulmonary gas exchange was measured breath-by-breath, using a portable telemetric system during maximal incremental exercise testing on a cycle ergometer. Statistical analysis included Shapiro-Wilk test follow by ANOVA two way repeated measures. Results: We observed a decrease in HbA1c (8.1±1.6 to 7.3±1.2%), cholesterol (198.38.1±50.3 to 186.8±35.1 mg/dL) and HOMA IR (6.4±6.8 to 5.0±1.4) in the CART-G compared to the SG. There was no significant difference in fasting plasma glucose. Although body weight did not significantly change after training, skinfold measurements indicated decreased body fat in the CART-G only. CART significantly enhanced muscle strength (p&lt;0.05) (peak torque: 135.5±4 to 159.7±47.7 N.m) compared to the SG (Peak torque: 145.3±47.9 to 143±42.2 N.m). CART was also associated with a significant increase in peak oxygen consumption, from 22.9±6.1 to 27.2±4.7 ml•kg –1 •min –1 compared to the SG, from 21.7±4.5 to 21±3.3 ml•kg –1 •min –1 as well as the maximal workload (124.6±29.1 to 149.9±29 watts) compared to the SG (123.6±36.9 to 122.1±32.9 watts). Conclusion: We concluded that CART is an important intervention strategy, producing both physiologic and functional improvements, in patients with diabetes.

Community Trial of a Faith-Based Lifestyle Intervention to Prevent Diabetes Among African-Americans.

NCT01730196.