24-h Glucose Profiles Research Articles

Acute Effect of Imeglimin Add-on Therapy on 24-h Glucose Profile and Glycemic Variability in Patients with Type 2 Diabetes Receiving Metformin.

Imeglimin is a novel antidiabetic drug with insulinotropic and insulin-sensitizing effects that targets mitochondrial bioenergetics. We investigated acute effects of add-on therapy with imeglimin to preceding metformin on the 24-h glucose profile and glycemic variability assessed by continuous glucose monitoring (CGM) in patients with type 2 diabetes. We studied 30 outpatients with type 2 diabetes inadequately controlled with metformin. CGM was used for 14 days straight during the research period. Imeglimin 2,000 mg/day was started on day 7 after initiating CGM. Several CGM parameters were compared between days 4-6 (prior to imeglimin treatment) and 11-13 (following the initiation of imeglimin treatment). After treatment with imeglimin, 24-h mean glucose was acutely decreased from 161.6 ± 48.0 mg/dL to 138.9 ± 32.2 mg/dL (p < 0.0001), while time in range (i.e., at a glucose level of 70-180 mg/dL) was significantly increased from 69.9 ± 23.9% to 80.6 ± 21.0% (p < 0.0001). Addition of imeglimin to metformin significantly decreased the standard deviation (SD) of 24-h glucose and mean amplitude of glycemic excursions, 2 indexes of glycemic variability. Baseline serum high-density lipoprotein (HDL) cholesterol was negatively correlated with changes in mean 24-h glucose (r = -0.3859, p = 0.0352) and those in SD (r = -0.4015, p = 0.0309). Imeglimin add-on therapy to metformin acutely lowered 24-h glucose levels and improved glycemic variability in patients with type 2 diabetes on metformin. A higher serum HDL cholesterol at baseline was associated with a better response to acute effects of imeglimin on 24-h glucose levels and glycemic variability.

Machine Learning-Based Prediction of Large-for-Gestational Age Infants in Mothers with Gestational Diabetes Mellitus.

Large-for-gestational-age (LGA), one of the most common complications of gestational diabetes mellitus (GDM), has become a global concern. The predictive performance of common continuous glucose monitoring (CGM) metrics for LGA is limited. We aimed to develop and validate an artificial intelligence (AI) based model to determine the probability of women with GDM giving birth to LGA infants during pregnancy using CGM measurements together with demographic data and metabolic indicators. A total of 371 women with GDM from a prospective cohort at a university hospital were included. CGM was performed during 20-34 gestational weeks, and glycemic fluctuations were evaluated and visualized in women with GDM who gave birth to LGA and non-LGA infants. A convolutional neural network (CNN)-based fusion model was developed to predict LGA. Comparisons among the novel fusion model and three conventional models were made using the area under the receiver-operating characteristic curve (AUCROC) and accuracy. Overall, 76 (20.5%) out of 371 GDM women developed LGA neonates. The visualized 24-h glucose profiles differed at midmorning. This difference was consistent among subgroups categorized by pregestational BMI, therapeutic protocol and CGM administration period. The AI based fusion prediction model using 24-h CGM data and 15 clinical variables for LGA prediction (AUCROC 0.852, 95% CI 0.680-0.966, accuracy 84.4%) showed superior discriminative power compared with the three classic models. We demonstrated better performance in predicting LGA infants among women with GDM using the AI based fusion model. The characteristics of the CGM profiles allowed us to determine the appropriate window for intervention.

24-h Glucose profile of patients with gestational diabetes mellitus and comparison with pregnant women with normoglycemia

24-h Glucose profile of patients with gestational diabetes mellitus and comparison with pregnant women with normoglycemia

Effects of reducing free sugars on 24-hour glucose profiles and glycemic variability in subjects without diabetes.

The Western diet, especially beverages and high processed food products, is high in sugars which are associated with the development of obesity and diabetes. The reduction of refined carbohydrates including free and added sugars improves glycemic control in individuals with diabetes, but the data regarding effects in subjects without diabetes are limited. This study aimed to evaluate the effects of reducing free sugar intake on 24-h glucose profiles and glycemic variability using continuous glucose monitoring (CGM). In the randomized controlled study, 21 normal weight and overweight/obese subjects (BMI 18-40 kg/m2) without diabetes were assigned to a 4-week reduced-sugar (RS) diet or control diet after a 2-week baseline phase. During the baseline phase, all participants were advised not to change their habitual diet. During the intervention phase, RS participants were asked to avoid added sugar and white flour products, whereas participants of the control group were requested to proceed their habitual diet. Anthropometric parameters and HbA1c were assessed before and at the end of the intervention phase. Interstitial glucose was measured using continuous glucose monitoring (CGM), and the food intake was documented by dietary records for 14 consecutive days during the baseline phase and for the first 14 consecutive days during the intervention phase. Mean 24-h glucose as well as intra- and inter-day indices of glucose variability, i.e., standard deviation (SD) around the sensor glucose level, coefficient of variation in percent (CV), mean amplitude of glucose excursions (MAGE), continuous overlapping net glycemic action (CONGA), and mean absolute glucose (MAG), were calculated for the baseline and intervention phases. During the intervention, the RS group decreased the daily intake of sugar (i.e., -22.4 ± 20.2 g, -3.28 ± 3.61 EN %), total carbohydrates (-6.22 ± 6.92 EN %), and total energy intake (-216 ± 108 kcal) and increased the protein intake (+2.51 ± 1.56 EN %) compared to the baseline values, whereby this intervention-induced dietary changes differed from the control group. The RS group slightly reduced body weight (-1.58 ± 1.33 kg), BMI, total fat, and visceral fat content and increased muscle mass compared to the baseline phase, but these intervention-induced changes showed no differences in comparison with the control group. The RS diet affected neither the 24-h mean glucose levels nor intra- and inter-day indices of glucose variability, HbA1c, or diurnal glucose pattern in the within- and between-group comparisons. The dietary reduction of free sugars decreases body weight and body fat which may be associated with reduced total energy intake but does not affect the daily mean glucose and glycemic variability in individuals without diabetes. German Clinical Trials Register (DRKS); identifier: DRKS00026699.

The effects of early time restricted eating plus daily caloric restriction compared to daily caloric restriction alone on continuous glucose levels.

The median eating duration in the U.S. is 14.75h, spread throughout the period of wakefulness and ending before sleep. Food intake at an inappropriate circadian time may lead to adverse metabolic outcomes. Emerging literature suggests that time restricted eating (TRE) may improve glucose tolerance and insulin sensitivity. The aim was to compare 24-h glucose profiles and insulin sensitivity in participants after completing 12weeks of a behavioral weight loss intervention based on early TRE plus daily caloric restriction (E-TRE+DCR) or DCR alone. Eighty-one adults with overweight or obesity (age 18-50years, BMI 25-45kg/m2) were randomized to either E-TRE+DCR or DCR alone. Each participant wore a continuous glucose monitor (CGM) for 7days and insulin sensitivity was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) at Baseline and Week 12. Changes in CGM-derived measures and HOMA-IR from Baseline to Week 12 were assessed within and between groups using random intercept mixed models. Forty-four participants had valid CGM data at both time points, while 38 had valid glucose, insulin, HOMA-IR, and hemoglobin A1c (A1c) data at both timepoints. There were no significant differences in sex, age, BMI, or the percentage of participants with prediabetes between the groups (28% female, age 39.2±6.9years, BMI 33.8±5.7kg/m2, 16% with prediabetes). After adjusting for weight, there were no between-group differences in changes in overall average sensor glucose, standard deviation of glucose levels, the coefficient of variation of glucose levels, daytime or nighttime average sensor glucose, fasting glucose, insulin, HOMA-IR, or A1c. However, mean amplitude of glycemic excursions changed differently over time between the two groups, with a greater reduction found in the DCR as compared to E-TRE+DCR (p=0.03). There were no major differences between E-TRE+DCR and DCR groups in continuous glucose profiles or insulin sensitivity 12weeks after the intervention. Because the study sample included participants with normal baseline mean glucose profiles and insulin sensitivity, the ability to detect changes in these outcomes may have been limited.

Continuous Glucose Monitoring Metrics and Birth Weight: Informing Management of Type 1 Diabetes Throughout Pregnancy.

To determine gestational weekly changes in continuous glucose monitoring (CGM) metrics and 24-h glucose profiles and their relationship to infant birth weight in pregnant women with type 1 diabetes. An analysis of >10.5 million CGM glucose measures from 386 pregnant women with type 1 diabetes from two international multicenter studies was performed. CGM glucose metrics and 24-h glucose profiles were calculated for each gestational week, and the relationship to normal (10-90th percentile) and large (>90th percentile) for gestational age (LGA) birth weight infants was determined. Mean CGM glucose concentration fell and percentage of time spent in the pregnancy target range of 3.5-7.8 mmol/L (63-140 mg/dL) increased in the first 10 weeks of pregnancy and plateaued until 28 weeks of gestation, before further improvement in mean glucose and percentage of time in range until delivery. Maternal CGM glucose metrics diverged at 10 weeks of gestation, with significantly lower mean CGM glucose concentration (7.1 mmol/L; 95% CI 7.05-7.15 [127.8 mg/dL; 95% CI 126.9-128.7] vs. 7.5 mmol/L; 95% CI 7.45-7.55 [135 mg/dL; 95% CI 134.1-135.9]) and higher percentage of time in range (55%; 95% CI 54-56 vs. 50%; 95% CI 49-51) in women who had normal versus LGA. The 24-h glucose profiles were significantly higher across the day from 10 weeks of gestation in LGA. Normal birth weight is associated with achieving significantly lower mean CGM glucose concentration across the 24-h day and higher CGM time in range from before the end of the first trimester, emphasizing the need for a shift in clinical management, with increased focus on using weekly CGM glucose targets for optimizing maternal glycemia from early pregnancy.

Acute Effects of High-Intensity Interval Training on Diabetes Mellitus: A Systematic Review.

This study evaluated the scientific evidence on the acute effects of high-intensity interval training (HIIT) on biochemical, cardiovascular, and metabolic parameters in patients with diabetes mellitus. The research took place using two databases (PubMed and Google Scholar) with eligible studies conducted between 2010 and 2020, using the following keywords: (1) high-intensity training/exercise; (2) interval training/exercise; (3) HIIT/exercise; AND “diabetes”. Data extraction was then performed on the eligible studies through content analysis using the categories: author and year of publication; sample characteristics; methods and data collected; intervention protocol; and results found. Methodological quality was assessed using the PEDro scale. Fourteen studies were included, evaluating 168 people with diabetes (122/46 type 2/1) and 42 normoglycemic individuals, which evaluated markers such as capillary and fasting blood glucose, 24-h blood glucose profile, postprandial blood glucose, incidence, and prevalence of hyperglycemia, vascular function and pressure response and control of inflammatory markers. Physical exercise was found to have several acute beneficial effects on the health of the diabetic population, such as reduced capillary and postprandial blood glucose, blood glucose profile, and blood pressure. Moreover, HIIT seems to be a safe and effective alternative in glycemic control and associated factors, superior to continuous moderate-intensity training.

Continuous Glucose Monitoring in Pregnancy: Importance of Analyzing Temporal Profiles to Understand Clinical Outcomes.

OBJECTIVETo determine if temporal glucose profiles differed between 1) women who were randomized to real-time continuous glucose monitoring (RT-CGM) or self-monitored blood glucose (SMBG), 2) women who used insulin pumps or multiple daily insulin injections (MDIs), and 3) women whose infants were born large for gestational age (LGA) or not, by assessing CGM data obtained from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT).RESEARCH DESIGN AND METHODSStandard summary metrics and functional data analysis (FDA) were applied to CGM data from the CONCEPTT trial (RT-CGM, n = 100; SMBG, n = 100) taken at baseline and at 24- and 34-weeks’ gestation. Multivariable regression analysis determined if temporal differences in 24-h glucose profiles occurred between comparators in each of the three groups.RESULTSFDA revealed that women using RT-CGM had significantly lower glucose (0.4–0.8 mmol/L [7–14 mg/dL]) for 7 h/day (0800 h to 1200 h and 1600 h to 1900 h) compared with those with SMBG. Women using pumps had significantly higher glucose (0.4–0.9 mmol/L [7–16 mg/dL]) for 12 h/day (0300 h to 0600 h, 1300 h to 1800 h, and 2030 h to 0030 h) at 24 weeks with no difference at 34 weeks compared with MDI. Women who had an LGA infant ran a significantly higher glucose by 0.4–0.7 mmol/L (7–13 mg/dL) for 4.5 h/day at baseline, by 0.4–0.9 mmol/L (7–16 mg/dL) for 16 h/day at 24 weeks, and by 0.4–0.7 mmol/L (7–13 mg/dL) for 14 h/day at 34 weeks.CONCLUSIONSFDA of temporal glucose profiles gives important information about differences in glucose control and its timing, which are undetectable by standard summary metrics. Women using RT-CGM were able to achieve better daytime glucose control, reducing fetal exposure to maternal glucose.

Mechanism of Action of Inhaled Insulin on Whole Body Glucose Metabolism in Subjects with Type 2 Diabetes Mellitus

In the current study we investigate the mechanisms of action of short acting inhaled insulin Exubera®, on hepatic glucose production (HGP), plasma glucose and free fatty acid (FFA) concentrations. 11 T2D (Type 2 Diabetes) subjects (age = 53 ± 3 years) were studied at baseline (BAS) and after 16-weeks of Exubera® treatment. At BAS and after 16-weeks subjects received: measurement of HGP (3-3H-glucose); oral glucose tolerance test (OGTT); and a 24-h plasma glucose (24-h PG) profile. At end of study (EOS) we observed a significant decrease in fasting plasma glucose (FPG, 215 ± 15 to 137 ± 11 mg/dl), 2-hour plasma glucose (2-h PG, 309 ± 9 to 264 ± 11 mg/dl), glycated hemoglobin (HbA1c, 10.3 ± 0.5% to 7.5 ± 0.3%,), mean 24-h PG profile (212 ± 17 to 141 ± 8 mg/dl), FFA fasting (665 ± 106 to 479 ± 61 μM), post-OGTT (433 ± 83 to 239 ± 28 μM), and triglyceride (213 ± 39 to 120 ± 14 mg/dl), while high density cholesterol (HDL-C) increased (35 ± 3 to 47 ± 9 mg/dl). The basal HGP decreased significantly and the insulin secretion/insulin resistance (disposition) index increased significantly. There were no episodes of hypoglycemia and no change in pulmonary function at EOS. After 16-weeks of inhaled insulin Exubera® we observed a marked improvement in glycemic control by decreasing HGP and 24-h PG profile, and decreased FFA and triglyceride concentrations.

Efficacy and Safety of Tofogliflozin on 24-h Glucose Profile Based on Continuous Glucose Monitoring: Crossover Study of Sodium-Glucose Cotransporter 2 Inhibitor.

Background: To compare the impact of two sodium-glucose cotransporter 2 (SGLT2) inhibitors, tofogliflozin and ipragliflozin, on hypoglycemia in patients with type 2 diabetes mellitus (T2DM), treated with sulfonylureas. Methods: Thirty patients with T2DM were allocated to treatment with either 20 mg/day tofogliflozin or 50 mg/day ipragliflozin and underwent continuous glucose monitoring (CGM) for 5 days at three times in a crossover manner. Results: The percent time spent at glucose <70 mg/dL per 24 h was 0.48, 2.77, and 0.06%, before treatment with SGLT2 inhibitors and treatment with ipragliflozin and tofogliflozin, respectively (P = 0.1135, difference between SGLT2 inhibitors). The addition of either ipragliflozin or tofogliflozin to sulfonylureas markedly and significantly improved other CGM-derived parameters, including average plasma glucose, standard deviation of glucose, mean postprandial glucose excursion, percent time with glucose >140, >180 mg/dL, and >200 mg/dL, area over the curve <70, area under the curve >140, >180, and >200, and maximum and minimum plasma glucose. However, there were no significant differences in these parameters between the two SGLT2 inhibitors. Conclusions: Based on the CGM, the addition of tofogliflozin to sulfonylureas tended to decrease the percent time spent in hypoglycemia in T2DM patients. The addition of SGLT2 inhibitors to sulfonylureas improved the average glucose level and reduced glucose fluctuations without increasing the time in hypoglycemia.

2266-PUB: Effects of Combined Exercise Protocols on Glucose Variability in Patients with Autoimmune Diabetes on CSII Therapy

Physical exercise may profoundly affect glucose variability (GV) in insulinopenic diabetes leading to both hypo- and hyperglycemia and feeling of discomfort reported by the patients after work out. Even if combined training reportedly reduces GV, an ideal training protocol is still not established in these patients. The aim of this study was to evaluate the effects of different combinations of continuous aerobic exercise (CON) and high intensity interval training (HIIT) on GV during a 24-h period after work out. A cross-over study was conducted on 14 outpatients [male 50%, mean age 31.9 (8.1) y, BMI 22.1 (2.5) Kg/m2] with either T1D (n=10) or LADA (n=4) on continuous subcutaneous insulin infusion (CSII) therapy [4 (3.9) y]. Data from flash glucose monitoring were collected for 72 h before work out. After different sequences of HIIT and CON work out (HIIT followed by CON, HIIT-CON; and CON followed by HIIT, CON-HIIT), 24-h glucose profiles were acquired. Several indices of GV and predictors of hypo-/hyperglycemia were analyzed. Indices of GV revealed no statistically significant difference when compared to baseline GV [mean -0.38 (1.85) vs. -0.43 (1.66); SD 0.02 (1.06) vs. -0.04 (0.94); CONGA: -0.18 (1.63) vs. -0.36 (1.69); MAG -0.12 (0.44) vs. -0.21 (0.47); MAGE 0.73 (1.65) vs. 1.11 (0.84); LBGI: 1.28 (6.83) vs. 1.71 (5.43); HBGI -0.18 (5.34) vs. -1.03 (4.89); HIIT-CON delta vs. baseline and CON-HIIT delta vs. baseline, respectively]. Moreover, time spent in &amp;lt;70 mg/dl and in &amp;gt;180 mg/dl 24 h after either HIIT-CON or CON-HIIT training was comparable to baseline [for &amp;lt;70 mg/dL: baseline 10.4% (11.6), HIIT-CON 13.3% (13.9), CON-HIIT 12.4% (10.2); for &amp;gt;180 mg/dl: baseline 27.2% (22.7), HIIT-CON 22.6% (21.1), CON-HIIT 22.2% (16.8)]. The comparison between HIIT-CON and CON-HIIT also showed no differences in GV. Thus, a standardized combined work out (either HIIT-CON or CON-HIIT) avoids late glycemic fluctuations and dangerous hypo-/hyperglycemia in T1D and LADA patients on CSII therapy. Disclosure A. Cignarelli: Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S. G. Lisco: None. L. Di Gioia: None. A. Natalicchio: Other Relationship; Self; Novo Nordisk Inc., Sanofi-Aventis. S. Perrini: None. L. Laviola: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc. Board Member; Self; AstraZeneca, Roche Diabetes Care, Sanofi-Aventis. Speaker's Bureau; Self; Medtronic, Mundipharma, Takeda Pharmaceutical Company Limited. F. Giorgino: Advisory Panel; Self; Aegerion Pharmaceuticals, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, MedImmune, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Roche Diabetes Care, Sanofi. Consultant; Self; Roche Diabetes Care, Sanofi. Research Support; Self; Eli Lilly and Company, LifeScan, Inc., Takeda Pharmaceutical Company Limited. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Sanofi.

Minimal effect of walking before dinner on glycemic responses in type 2 diabetes: outcomes from the multi-site E-PAraDiGM study

To examine the effect of walking before dinner on 24-h glycemic control in individuals with type 2 diabetes using the standardized multi-site Exercise-Physical Activity and Diabetes Glucose Monitoring (E-PAraDiGM) Protocol. Eighty participants were studied under two conditions (exercise vs. non-exercise control) separated by 72h in a randomized crossover design. Each condition lasted 2 days during which standardized meals were provided. Exercise consisted of 50min of treadmill walking at 5.0km/h before the evening meal, while control involved 50min of sitting. The primary outcome measure was mean glucose during the 24-h period following exercise (or sitting) measured by continuous glucose monitoring. Of the 80 participants who were initially randomized, 73 completed both exercise and control. Sixty-three participants [29 males, 34 females; age = 64 ± 8years, body mass index = 30.5 ± 6.5kg/m2 and HbA1c = 51 ± 8mmol/mol (6.8 ± 0.7%), mean ± SD] complied with the standardized diets and had complete continuous glucose monitoring data. Exercise did not affect mean 24-h glucose compared to control (0.03mmol/L; 95% CI - 0.17, 0.22, P = 0.778) but individual differences between conditions ranged from - 2.8 to +1.8mmol/L. Exercise did not affect fasting glucose, postprandial glucose or glucose variability. Glucose concentrations measured by continuous glucose monitoring were reduced during the 50min of walking in exercise compared to sitting in control (- 1.56mmol/L; 95% CI - 2.18, - 0.95, p < 0.001). Contrary to previous acute exercise studies, 50min of walking before dinner in the E-PAraDiGM protocol did not affect 24-h glucose profiles. However, highly heterogeneous responses to exercise were observed. NCT02834689.

Effects of a large breakfast versus large dinner on 24-h blood glucose profiles during a day of prolonged sedentary behaviour

Effects of a large breakfast versus large dinner on 24-h blood glucose profiles during a day of prolonged sedentary behaviour

Effects of non-nutritive (artificial vs natural) sweeteners on 24-h glucose profiles.

Replacing nutritive sweetener with non-nutritive sweeteners (NNS) has the potential to improve glycaemic control. The objective of this study was to investigate the effects of consuming artificial NNS (that is, aspartame), natural NNS (that is, monk fruit and stevia), and sucrose-sweetened beverages on 24-h glucose profiles. Ten healthy males took part in this randomised, crossover study with the following four treatments: aspartame-, monk fruit-, stevia-, and sucrose- (65 g) sweetened beverages. Participants were asked to consume the test beverage as a preload mid-morning. Medtronic iPro2 continuous glucose monitoring system was used to measure mean 24-h glucose, incremental area under the curve (iAUC) and total area under the curve (AUC) for glucose, and 24-h glycaemic variability. Overall no significant differences were found in mean 24-h glucose, iAUC and total AUC for glucose, and 24-h glycaemic variability between the four test beverages. Twenty-four-hour glucose profiles did not differ between beverages sweetened with non-nutritive (artificial vs natural) and nutritive sweeteners. The simple exchange of a single serving of sucrose-sweetened beverage with NNS over a day appears to have minimal effect on 24-h glucose profiles in healthy males.

Comparison of Insulin Glargine 300 Units/mL and 100 Units/mL in Adults With Type 1 Diabetes: Continuous Glucose Monitoring Profiles and Variability Using Morning or Evening Injections.

The objective of this study was to compare glucose control in participants with type 1 diabetes receiving insulin glargine 300 units/mL (Gla-300) or glargine 100 units/mL (Gla-100) in the morning or evening, in combination with mealtime insulin. In this 16-week, exploratory, open-label, parallel-group, two-period crossover study (clinicaltrials.gov identifier NCT01658579), 59 adults with type 1 diabetes were randomized (1:1:1:1) to once-daily Gla-300 or Gla-100 given in the morning or evening (with crossover in the injection schedule). The primary efficacy end point was the mean percentage of time in the target glucose range (80-140 mg/dL), as measured using continuous glucose monitoring (CGM), during the last 2 weeks of each 8-week period. Additional end points included other CGM glycemic control parameters, hypoglycemia (per self-monitored plasma glucose [SMPG]), and adverse events. The percentage of time within the target glucose range was comparable between the Gla-300 and Gla-100 groups. There was significantly less increase in CGM-based glucose during the last 4 h of the 24-h injection interval for Gla-300 compared with Gla-100 (least squares mean difference -14.7 mg/dL [95% CI -26.9 to -2.5]; P = 0.0192). Mean 24-h glucose curves for the Gla-300 group were smoother (lower glycemic excursions), irrespective of morning or evening injection. Four metrics of intrasubject interstitial glucose variability showed no difference between Gla-300 and Gla-100. Nocturnal confirmed (<54 mg/dL by SMPG) or severe hypoglycemia rate was lower for Gla-300 participants than for Gla-100 participants (4.0 vs. 9.0 events per participant-year; rate ratio 0.45 [95% CI 0.24-0.82]). Less increase in CGM-based glucose levels in the last 4 h of the 24-h injection interval, smoother average 24-h glucose profiles irrespective of injection time, and reduced nocturnal hypoglycemia were observed with Gla-300 versus Gla-100.

The effect of alternate-day caloric restriction on the metabolic consequences of 8 days of bed rest in healthy lean men: a randomized trial.

Alternate-day caloric restriction without overall energy reduction does not ameliorate the metabolic impairment induced in lean men by 8 days of bed rest.

Pharmacological characterization and antidiabetic activity of a long-acting glucagon-like peptide-1 analogue conjugated to an antithrombin III-binding pentasaccharide.

To examine the biological characteristics of a novel glucagon-like peptide-1 (GLP-1) conjugate, in which an antithrombin III (ATIII)-binding pentasaccharide is conjugated to d-Ala(8) GLP-1 using a tetraethylene glycol linker. We assessed GLP-1 receptor binding, cAMP generation and insulin secretory activity of the GLP-1 conjugate in vitro. Circulating half-life, glucose homeostatic and subchronic therapeutic effectiveness were then examined in vivo. The half-life of the GLP-1 conjugate in mice was ∼11 h. In vitro insulin secretion from clonal β cells and islets was increased (p < 0.001) by the conjugate. The conjugate had half maximum effective concentration values of 1.3 × 10(-7) and 9.9 × 10(-8) M for displacement of (125) I-GLP-1 in competitive GLP-1 receptor binding and cAMP generation, respectively. Glucose tolerance in normal mice, immediately and 4 h after conjugate injection, resulted in significant (p < 0.001) improvements in blood glucose. These effects persisted for >48 h after administration. Daily treatment (21 days) of high-fat-fed and ob/ob mice with 25 nmol/kg conjugate resulted in significant improvement in glucose tolerance (p < 0.001) and reductions in glycated haemoglobin (HbA1c; p < 0.01) equivalent to or better than with exenatide or liraglutide. Treatment of C57BL/KsJ db/db mice for 15 days with 100 nmol/kg conjugate significantly (p < 0.001) reduced glucose and raised plasma insulin. Oral glucose tolerance was significantly (p < 0.001) improved and both 24-h glucose profile (p < 0.001) and HbA1c levels (p < 0.001) were reduced. Islet size (p < 0.001) and pancreatic insulin content were increased without change of islet cell proliferation or apoptosis. These data show that d-Ala(8) GLP-1(Lys(37) ) pentasaccharide exerts significant antidiabetic actions and has a projected pharmacokinetic/pharmacodynamic profile that merits further evaluation in humans for a possible once-weekly dosing regimen.

The impact of a low glycemic index (GI) breakfast and snack on daily blood glucose profiles and food intake in young Chinese adult males

ObjectiveLow glycemic index (GI) foods have been suggested to minimize large fluctuations in blood glucose levels and reduce food intake. However, the majority of studies have been conducted on Caucasian populations with limited data on Asians. The objective of this study was to investigate how the provision of a low GI breakfast and afternoon snack affected daily blood glucose profiles and food intake. Materials and methodsIn a randomized, controlled crossover non blind design, 11 healthy Chinese male adults (body mass index 22.4 ± 1.3 kg m−2) attended two sessions where they consumed either a high or low GI breakfast and afternoon snack, and a standardized buffet lunch. Daily changes in glycemic response (GR) were measured using the Medtronic MiniMed (Northridge, CA) iPro™2 continuous glucose monitoring system (CGMS). The GR was further calculated to obtain the incremental area under the curve (IAUC). Glycemic variability was calculated as mean amplitude of glycemic excursion (MAGE) and energy intake (kcal) was measured quantitatively at the buffet lunch. ResultsCompared to the high GI intervention, the low GI intervention significantly reduced the GR following breakfast (p = 0.02), lunch (p = 0.02) and dinner (p = 0.05). The low GI treatment showed a reduction in daily AUC (p = 0.03). There was a significant reduction in IAUC after a low GI breakfast compared to the high GI breakfast (p = 0.03). The low GI breakfast resulted in a significantly lower food intake at lunch and a resulting decreased energy intake of 285 kcal (p = 0.02). The MAGE was significantly lower during the entire low GI treatment (p = 0.03). ConclusionsConsumption of a low GI breakfast and afternoon snack was capable of attenuating 24-h blood glucose profiles, minimize glycemic excursions and reduce food intake in healthy Asian males. This simple dietary intervention may be an acceptable approach in improving overall glycemia and energy balance in Asians. Clinical trial registration numberNCT02340507

Continuous Glucose Monitoring During Basal-Bolus Therapy Using Insulin Glargine 300UmL(-1) and Glargine 100UmL (-1) in Japanese People with Type 1 Diabetes Mellitus: A Crossover Pilot Study.

IntroductionNew insulin glargine 300 U mL−1 (Gla-300) is a basal insulin that shows more stable and prolonged pharmacokinetic and pharmacodynamic profiles than insulin glargine 100 U mL−1 (Gla-100). This study used continuous glucose monitoring (CGM) to compare 24-h glucose profiles in a Japanese population using Gla-300 versus Gla-100.MethodsThis was an exploratory 8.4-week, single-center, 2-sequence, 2-period, open-label crossover study. Japanese adults with type 1 diabetes mellitus (T1DM) treated with basal–bolus insulin, with glycated hemoglobin (HbA1c) 6.5–10.0% and median fasting self-monitored plasma glucose concentration ≤13 mmol L−1, were randomized to Gla-300 followed by Gla-100 (subgroup 1) or vice versa (subgroup 2), with no washout period. CGM was performed on the last 3 days of the screening period and each treatment period. Primary endpoint was comparison of 24-h glucose variability (area under the curve [AUC]mean_24 h) on the second day of each CGM measurement with Gla-300 versus Gla-100. Baseline and end of treatment period values for HbA1c, fasting plasma glucose (FPG) and daily basal/mealtime insulin doses were recorded. Hypoglycemia and adverse events (AEs) were recorded.ResultsTwenty participants were randomized (10 to subgroup 1 and 10 to subgroup 2). Participants showed comparable glucose variability over 24 h (AUCmean_24 h during treatment with Gla-300 or Gla-100 (treatment ratio 0.96; 90% confidence interval 0.79, 1.16). HbA1c and FPG were generally stable across both treatment periods. There was a trend towards fewer participants experiencing ≥1 hypoglycemia event at any time (24 h) and at night (00:00–05:59 h) with Gla-300 versus Gla-100. Treatment-emergent AEs, reported by 9/20 (45%) and 4/20 (20%) participants during Gla-300 and Gla-100 treatment, respectively, were unrelated to study medication.ConclusionsIn this cohort of Japanese people with T1DM, no between-treatment difference was observed in glucose variability with Gla-300 versus Gla-100, as measured by CGM. There was a trend for less hypoglycemia with Gla-300, particularly at night, versus Gla-100. Both treatments were well tolerated.FundingSanofi, Tokyo, Japan. Clinical trial registration: NCT01676233, ClinicalTrials.gov.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-015-0115-1) contains supplementary material, which is available to authorized users.

Contributions of Basal Glucose and Postprandial Glucose Concentrations to Hemoglobin A1c in the Newly Diagnosed Patients with Type 2 Diabetes--the Preliminary Study.

The aim of this preliminary study is to investigate contributions of basal glucose (BG) and postprandial glucose (PPG) increments to overall hyperglycemia in newly diagnosed patients with type 2 diabetes mellitus (T2DM). We evaluated the relative contributions of BG and PPG to overall hyperglycemia in 59 newly diagnosed T2DM patients according to BG baseline value of 6.1 mmol/L and 24-h glucose profiles of normal glucose tolerance (NGT) subjects obtained by continuous glucose monitoring as baseline, respectively. When the baseline was 24-h glucose profiles of the NGT subjects, the relative contributions of PPG in the T2DM patients with hemoglobin A1c (HbA1c) levels of ≤ 7.0%, 7.0-9.0%, and >9.0% were 57.58%, 44.69%, and 21.56%, respectively. When the baseline value was equal to 6.1 mmol/L, the relative contributions of PPG in the T2DM patients with HbA1c levels of ≤ 7.0%, 7.0-9.0%, and >9.0% were 77.23%, 53.43%, and 22.78%, respectively. Compared with the 24-h glucose profiles of the NGT subjects as the baseline, the relative contribution of PPG was overestimated by about 10-20% in the T2DM patients with HbA1c levels of ≤ 9.0% when 6.1 mmol/L was chosen as the baseline. In the newly diagnosed T2DM patients with mild hyperglycemia, PPG is a predominant contributor, whereas the relative contributions of BG gradually increase from mild to severe hyperglycemia and obviously exceed PPG in the T2DM patients with HbA1c levels of >9.0%. This finding implies that the initial pharmacotherapy may target PPG in those patients with mild hyperglycemia and target BG in those patients with severe hyperglycemia.