Postprandial Glucose Excursions Research Articles

Effects of postprandial exercise timing on blood glucose and fluctuations in patients with type 2 diabetes mellitus.

The aim of this study was to assess how moderate-intensity aerobic exercise performed 45 minutes and 90 minutes after a meal affects blood glucose levels and fluctuations in individuals diagnosed with type 2 diabetes mellitus (T2DM). Twenty-two patients with T2DM, who were solely receiving oral hypoglycemic medication, were enrolled and divided randomly into two categories: those exercising 45 minutes after a meal (45-minute postprandial exercise group) and those exercising 90 minutes post-meal (90-minute postprandial exercise group). Both groups engaged in a 30-minute session of moderate-intensity aerobic stationary bike exercise following breakfast. This aerobic exercise regimen consisted of two stages, with the groups switching exercise timings after the initial phase. Continuous glucose monitoring (CGM) was utilized to evaluate the blood glucose levels and fluctuations in the participants. After breakfast, both overall daily blood glucose levels and the area under the curve for blood glucose following breakfast were reduced in the 45-minute postprandial exercise group compared to the 90-minute postprandial exercise group. The 45-minute postprandial exercise group demonstrated greater time spent within the target glucose range and less time above the target range than the 90-minute postprandial exercise group. Additionally, measures such as standard deviation, mean amplitude of glycemic excursions, largest amplitude of glycemic excursions, and postprandial glucose excursion for breakfast, peak postprandial glucose levels, and duration of elevated glucose levels were all lower in the 45-minute postprandial exercise group compared to the 90-minute postprandial exercise group. Moderate-intensity aerobic exercise lasting 45 minutes after meals was found to be more efficient in decreasing blood glucose levels and minimizing fluctuations compared to exercising 90 minutes after meals in patients with T2DM. Additionally, it notably reduced the peak in blood glucose levels after meals.

Post Prandial Glucose Turnover Differs Between Adolescents & Adults with Type 1 Diabetes: Triple Tracer Mixed Meal Study.

Insulin sensitivity (SI) varies with age in Type 1 diabetes (T1D). To compare postprandial glucose turnover and insulin sensitivity between adolescents and adults with T1D. Cross-sectional comparison. Clinical Research Unit. 21 early adolescents with T1D (T1D-adol) [12F; age: 11.5 ± 0.5yrs.; BMI: 19 ± 2 kg/m2], 13 adults with T1D (T1D-adult) [5F; 37.8 ± 9.1yrs.; BMI: 27 ± 2 kg/m2] and 14 anthropometrically matched adults without diabetes (ND) [7F; 26.9 ± 7.0yrs.; BMI: 25 ± 2.5 kg/m2]. Triple-tracer mixed meal study and oral glucose models. SI between T1D-adol and T1D-adult. Post-prandial glucose excursions were not different in T1D-adol vs T1D-adult (p = 0.111) but higher than in ND (p < 0.01). Insulin excursions were also similar in T1D-adol vs. T1D-adult (p = 0.600) and they were both lower (p < 0.05) compared to ND, while glucagon excursions were lower (p < 0.01) in T1D-adol than in T1D-adult and ND. Integrated rates of endogenous glucose production and glucose disappearance were lower in T1D-adol than in T1D-adult and in ND vs. T1D-adult but did not differ between T1D-adol and ND. Meal glucose appearance did not differ between groups. Insulin sensitivity (SI) in T1D-adol vs ND was similar (p = 0.299). However, SI was higher in T1D-adol and ND vs. T1D-adult (p < 0.01). We report differences in parameters of postprandial glucose turnover and insulin sensitivity between adults and early adolescents with T1D that could, at least in part, be due to the shorter duration of diabetes among T1D-adol. These data support the concept that over time with T1D endogenous glucose production increases and SI deteriorates.

Oxytocin does not acutely improve glucose tolerance in men with type 2 diabetes.

To assess oxytocin's acute glucoregulatory impact in men with type 2 diabetes in the context of our previous findings that oxytocin improves β-cell responsivity in healthy men. In a double-blind, crossover comparison, intranasal oxytocin (24 IU) and placebo, respectively, were administered to 25 fasted men with non-insulin-treated type 2 diabetes (age ± standard error of the mean, 63.40 ± 1.36 years; body mass index, 27.77 ± 0.66 kg/m2; HbA1c, 6.86% ± 0.08%; Homeostatic Model Assessment of Insulin Resistance (HOMA-IR, 3.44 ± 0.39) 60 minutes before an oral glucose tolerance test (oGTT). Key outcomes were compared with previous results in men with normal weight or obesity. Oxytocin compared with placebo increased plasma oxytocin concentrations and reduced the heart rate, but did not alter glucose metabolism in the 3 hours after oGTT onset (area under the curve, glucose, 2240 ± 80.5 vs. 2190 ± 69.5 mmol/L × min; insulin, 45 663 ± 4538 vs. 44 343 ± 4269 pmol/L × min; C-peptide, 235 ± 5.1 vs. 231 ± 15.9 nmol/L × min). This outcome contrasts with the oxytocin-induced attenuation of early postprandial glucose excursions in normal-weight individuals, but is in line with the absence of respective effects in men with obesity. We conclude that insulin resistance in type 2 diabetes is associated with decreased sensitivity to the acute glucoregulatory effect of oxytocin in male individuals.

The role of glucagon-like peptide 1 in the postprandial effects of metformin in type 2 diabetes: a randomized crossover trial.

Although metformin is widely used for treatment of type 2 diabetes (T2D), its glucose-lowering mechanism remains unclear. Using the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) antagonist exendin(9-39)NH2, we tested the hypothesis that postprandial GLP-1-mediated effects contribute to the glucose-lowering potential of metformin in T2D. In a randomized, placebo-controlled, double-blind, crossover study, 15 individuals with T2D (median HbA1c 50 mmol/mol [6.7%], body mass index 30.1 kg/m2, age 71 years) underwent, in randomized order, 14 days of metformin and placebo treatment, respectively. Each treatment period was preceded by 14 days without any glucose-lowering medicine and concluded by two 4 h mixed meal tests performed in randomized order and separated by >24 h with either continuous intravenous exendin(9-39)NH2 or saline infusion. Compared to placebo, metformin treatment lowered fasting plasma glucose (mean of differences [MD] 1.4 mmol/L × min [95% CI 0.8-2.0]) as well as postprandial plasma glucose excursions during both saline infusion (MD 186 mmol/L × min [95% CI 64-307]) and exendin(9-39)NH2 infusion (MD 268 mmol/L × min [95% CI 108-427]). The metformin-induced improvement in postprandial glucose tolerance was unaffected by GLP-1R antagonization (MD 82 mmol/L × min [95% CI -6564-170]). Metformin treatment increased fasting plasma GLP-1 (MD 1.7 pmol/L × min [95% CI 0.39-2.9]) but did not affect postprandial GLP-1 responses (MD 820 pmol/L × min [95% CI -1750-111]). Using GLP-1R antagonization, we could not detect GLP-1-mediated postprandial glucose-lowering effect of metformin in individuals with T2D. We show that 2 weeks of metformin treatment increases fasting plasma GLP-1, which may contribute to metformin's beneficial effect on fasting plasma glucose in T2D. Trial registration: Clinicaltrials.gov NCT03246451.

Advanced hybrid closed loop (artificial pancreas) and carbohydrate count in type 1 diabetes

BACKGROUND: Postprandial Glucose Excursion (PPGE) control is one of the goals of diabetes therapy. Patients should count meal carbohydrates but it is often inaccurate. Automated Advanced Hybrid Closed Loop (AHCL) systems may overcome carbohydrate count mistakes and aid to improve PPGE control. OBJECTIVE: To evaluate the effect of switching from manual Sensor Augmented Pump (SAP) to AHCL on PPGE in Type 1 Diabetic (T1D) subjects. METHODS: In 15 T1D patients using manual SAP, the Area Under the Curve (AUC) after breakfast, lunch and dinner was calculated for two weeks before (T0), immediately (T1) and 3 months (T2) after switching to 780 G AHCL system. Total Daily Dose (TDD), Time Above/Below/In Range (TAR, TBR, TIR), BMI, A1c, lipid profile and Treatment Satisfaction Questionnaire (DTSQ) were considered. RESULTS: A significant reduction in AUC was observed for breakfast and dinner at T2 and for lunch and dinner at T1. TIR increased, while TAR and TBR reduced significantly from T0 to T1 and T2. For A1c, BMI and plasma lipids no statistically significant differences were observed, although A1c decreased from 7.2% to 6.8%. TDD increased significantly, due to the automatic correction boluses. DTSQ score at T2 was 33 (range 32–34, max 36). CONCLUSIONS: After switching to AHCL, PPGE decreased rapidly by automatic correction boluses, without weight gain. Meal management simplification and glucose control improvement were associated with high satisfaction scores.

Expert Opinion on Optimising Type2 Diabetes Treatment Using Fixed-Ratio Combination of Basal Insulin and GLP-1RA for Treatment Intensification and Simplification.

The management of type2 diabetes (T2D) often necessitates treatment intensification, and sometimes simplification to achieve glycaemic targets and mitigate complications. This expert opinion paper evaluates the use and positioning of the fixed-ratio combinations (FRCs) of basal insulin (BI) and glucagon-like peptide1 receptor agonists (GLP-1RAs) in optimising T2D management. On the basis of the evidence presented and discussions, these FRCs offer a promising approach for both treatment intensification and simplification in people with suboptimal glucose control despite receiving various therapies. In treatment intensification, FRCs provide a synergistic effect by addressing multiple pathophysiological defects contributing to hyperglycaemia. These FRCs effectively control both fasting and postprandial glucose (PPG) excursions, offering significantly improved glycaemic control with a lower hypoglycaemia risk and weight neutrality compared to traditional or complex insulin regimens. Moreover, the reduced injection frequency (once daily) and flexibility in the dosing schedule (with any major meal of the day) help mitigate patient resistance to insulin initiation or titration. This further reduces treatment burden, facilitating treatment adherence and enhancing patient convenience. These key benefits of FRCs over complex insulin regimens play a crucial role in long-term glycaemic management and overall treatment outcomes. Hence, the timely use of FRCs in the treatment algorithm for people with T2D represents a valuable strategy for optimising glycaemic control, addressing treatment barriers and enhancing patient-reported outcomes.

Time-in-Range With Insulin Versus Metformin in Gestational Diabetes Mellitus Using Continuous Glucose Monitoring: A Randomized Control Study at a Tertiary Care Centre in South India.

Background The prevalence of gestational diabetes mellitus (GDM) is increasing globally. When diet and lifestyle modifications are inadequate for control, managing GDM often involves insulin or metformin. Metformin's oral administration option improves patient compliance and acceptance, but concerns about its use persist, necessitating careful evaluation. Comparative studies between insulin and metformin in GDM are scarce. In pregnancies complicated by diabetes, precise glucose control is crucial for maternal-fetal well-being, and continuous glucose monitoring (CGM) plays a valuable role in achieving recommended targets. CGM provides comprehensive glucose profiles, including postprandial glucose excursions and details about time spent in hypoglycemia, euglycemia, and hyperglycemia. The time-in-range (TIR) metric, when used alongside A1C, offers more actionable information than A1C alone. To the best of our knowledge, no published trials compare TIR in GDM with metformin or insulin aspart/detemir, specifically focusing on CGM metrics. This randomized controlled trial (RCT) aims to assess TIR in women with GDM treated with either metformin or insulin. Materials and methods This study was a non-inferiority randomized control trial evaluating TIR in GDM using continuous glucose monitoring with metformin or insulin. Forty-four women with GDM were enrolled. The diagnosis of GDM was based on the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. CGM readings were collected for 14 days after sensor activation. Results In our study, 44 women with GDM completed the protocol, with 22 in the Metformin group and 22 in the Insulin group. Baseline characteristics did not differ between the groups. Age, BMI pre-gravid, BMI at 28 weeks, parity, family history of diabetes mellitus, previous history of GDM, glycated hemoglobin (HbA1c), oral glucose tolerance tests (OGTT) at zero hours, one hour, and two hours, as well as gestational weeks, did not significantly differ between the two groups. The metformin and insulin groups did not differ significantly in CGM metrics, including TIR, time above range, time below range, mean glucose, and glucose management indicator. Conclusion Based on our findings, the metformin and insulin groups did not differ in CGM metrics, including TIR, time above range, time below range, mean glucose, and glucose management indicator. In clinical practice, CGM metrics complement fasting blood glucose, postprandial glucose, and HbA1c as appropriate and useful clinical targets and outcome measurements. Metformin's oral administration option offers advantages such as improved patient compliance and acceptance in women with GDM.

Ultra rapid lispro improves postprandial glucose control versus lispro in combination with basal insulin: a study based on CGM in type 2 diabetes in China.

To evaluate the efficacy and safety of URLi (ultra rapid lispro insulin) compared to insulin lispro as bolus insulin with basal insulin using CGM in the individuals with type 2 diabetes(T2D) in China. This was a double-blind, randomized, parallel, prospective, phase 3 study. Subjects with uncontrolled T2D were recruited and randomized 1:2 into the insulin lispro and URLi groups. Subjects received a consistent basal insulin regimen during the study and self-administered insulin lispro or URLi before each meal throughout the treatment period. Subjects underwent a 3-day continuous glucose monitoring (CGM) at the baseline and endpoint respectively, and then CGM data were analyzed. The primary endpoint was to compare the difference in postprandial glucose (PPG) control using CGM between the two groups. A total of 57 subjects with T2D completed the study. Our CGM data showed that postprandial glucose excursions after breakfast (BPPGE) in the URLi group was lower than that in the insulin lispro group (1.59 ± 1.57 mmol/L vs 2.51 ± 1.73 mmol/L, p = 0.046). 1-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.37 ± 3.28 mmol/L vs 0.24 ± 2.58 mmol/L, p = 0.047). 2-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.12 ± 4.00 mmol/L vs 1.22 ± 2.90 mmol/L, p = 0.021). The mean HbA1c level decreased by 1.1% in the URLi group and 0.99% in the insulin lispro group, with no treatment difference (p = 0.642). In the CGM profile, TBR was not significantly different between the two groups (p = 0.743). The weight gain also did not differ between the two groups (p = 0.303). URLi can control breakfast PPG better than insulin lispro in adults with T2D in China, while it is non-inferior in improving HbA1c. The incidence of hypoglycemic and weight gain were similar between the two groups.

A Green Light-Activated Insulin Depot with Ultrafast In Vivo Efficiency in the Subcutaneous Space.

In this work, for the first time, we demonstrate light control of a therapeutic protein's release from a depot in the subcutaneous layer of the skin. The subcutaneous layer is a standard location for therapeutic protein depots due to its large size and ease of access, but prior attempts to utilize this space failed because insufficient light can reach this deeper layer. An analysis of existing biophysical literature suggested that an increase of photoactivation wavelength from 365 to 500 nm could allow an increase of depot irradiation in the subcutaneous by >100-fold. We therefore used a green light-activated thio-coumarin-based material and demonstrated robust release of a therapeutic, insulin, in response to skin illumination with an LED light source. We further demonstrated that this release is ultrafast, as fast or faster than any commercially used insulin, while maintaining the native insulin sequence. This release of insulin was then accompanied by a robust reduction in blood glucose, demonstrating the retention of bioactivity despite the synthetic processing required to generate the material. In addition, we observed that the material exhibits slow basal release of insulin, even in the absence of light, potentially through biochemical or photochemical unmasking of insulin. Thus, these materials can act much like the healthy pancreas does: releasing insulin at a slow basal rate and then, upon skin irradiation, releasing an ultrafast bolus of native insulin to reduce postprandial blood glucose excursions.

Usefulness of a New 75 g Glucose-and High Fat-Containing Cookie Meal Test to Investigate Abnormal Postprandial Glucose and Triglyceride Excursions

Usefulness of a New 75 g Glucose-and High Fat-Containing Cookie Meal Test to Investigate Abnormal Postprandial Glucose and Triglyceride Excursions

Blood Glucose Fluctuation Is Indicative of Adiposity

Introduction: Continuous glucose monitoring (CGM) system is an effective tool for assessing a person’s glycemic control in real-time, in a “free living condition”. Poor glycemic control is strongly linked to cardiovascular disease, obesity, and the pernicious deposition of fat in the abdominal region. Emerging data show that surges in glucose levels after a meal (postprandial glucose excursions) are more tightly linked to cardiovascular disease, insulin resistance, and diabetic complications than the traditional clinical measure of glycemic control using glycated hemoglobin (HbA1c). Therefore, the purpose of this study is to determine if daily glycemic variability as measured by CGM is an indicator of total and regional body fat distribution and how CGM compares with HbA1c measurements. Methods: Twenty-seven volunteers participated in the study (Male: 11, Female: 16, Age: 32.15 ± 14.55 years, BMI: 28.43 ± 7.30 kg/m2). Total body and regional fat distribution (android, gynoid, android/gynoid) were determined using dual-energy x-ray absorptiometry. Fasting blood glucose and glycated hemoglobin (HbA1c) were measured from collected blood samples. Glycemic variability was measured by CGM attached to the abdomen. Results: CGM glycemic variability was positively correlated with total body fat% (r= 0.4278; p= 0.0329), android fat% (r= 0.5313; p= 0.0063), and android/gynoid ratio (r= 0.5981; p= 0.0016). HbA1c was only positively correlated with android/ gynoid ratio (r= 0.5534; p= 0.0041). Conclusion: Higher blood glucose variability/fluctuation measured by CGM was associated with greater body fat, android fat, android/gynoid fat ratio, which are indicators of cardiovascular disease risks. Blood glucose fluctuation monitoring should be considered in blood glucose management. This study was funded by The University of Texas, El Paso Dodson Fund and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) - R01DK132430. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Canagliflozin or acarbose versus placebo to ameliorate post-bariatric hypoglycaemia - The HypoBar I randomized clinical trial protocol.

Post-bariatric hypoglycaemia (PBH) is a rare yet disabling clinical condition, mostly reported after Roux-en-Y gastric bypass (RYGB) surgery. RYGB is one of the most widely used and effective bariatric procedures. The pathophysiology of PBH remains unclear, and treatment options are limited in effectiveness and/or carry significant side effects. Acarbose slows carbohydrates digestion and absorption and is generally considered first-line pharmacological treatment for PBH but its gastrointestinal side effects limit patient compliance. Canagliflozin inhibits intestinal and renal sodium-dependent glucose absorption and reduces postprandial excursions of glucose, insulin and incretins after RYGB - effects that could be beneficial in ameliorating PBH. The trial aims to investigate how blood glucose levels are affected during daily living in subjects with PBH during treatment with canagliflozin or acarbose compared with placebo, and to study the meal-induced entero-endocrine mechanisms implied in the treatment responses. In a double-blinded, randomized, crossover clinical trial, HypoBar I will investigate the effectiveness in reducing the risk of PBH, safety, ambulatory glucose profile and entero-endocrine responses when PBH is treated with canagliflozin 300 mg twice daily during a 4-week intervention period, compared with acarbose 50 mg thrice daily or placebo. HypoBar I is approved by the Local regulatory entities. Results will be published in peer-reviewed journals. If effective, well-tolerated and safe, canagliflozin could be a novel treatment for people with PBH. HypoBar I might also unravel new mechanisms underlying PBH, potentially identifying new treatment targets. EudraCT number 2022-000157-87.

Assessing the temporal within-day glycemic variability during hospitalization in patients with type 2 diabetes patients using continuous glucose monitoring: a retrospective observational study

AimsFrequent and extensive within-day glycemic variability (GV) in blood glucose levels may increase the risk of hypoglycemia and long-term mortality in hospitalized patients with diabetes. We aimed to assess the amplitude and frequency of within-day GV in inpatients with type 2 diabetes and to explore the factors influencing within-day GV.MethodsWe conducted a single-center, retrospective observational study by analyzing hospital records and 10-day real-time continuous glucose monitoring data. Within-day GV was assessed using the coefficient of variation (%CV). The primary outcome was the amplitude and frequency of within-day GV. The frequency of within-day GV was assessed by the consecutive days (CD) of maintaining within the target %CV range after first reaching it (CD after first reaching the target) and the maximum consecutive days of maintaining within the target %CV range (Max-CD). The target %CV range was less than 24.4%. We evaluated the factors influencing within-day GV using COX regression and Poisson regression models.ResultsA total of 1050 cases were analyzed, of whom 86.57% reduced the amplitude of within-day GV before the sixth day of hospitalization. Of the 1050 hospitalized patients, 66.57% stayed within the target %CV range for less than two days after first reaching the target and 69.71% experienced a Max-CD of fewer than four days. Reducing the average postprandial glucose excursion (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.77–0.85; incidence rate ratios [IRR]: 0.72, 95% CI: 0.69–0.74) and the use of α-glucosidase inhibitors (IRR: 1.1, 95% CI: 1.01–1.18) and glucagon-like peptide-1 agonist (IRR: 1.30, 95% CI: 1.02–1.65) contributed to reducing the amplitude and decreasing the frequency of within-day GV. However, the use of insulin (HR: 0.64, 95% CI: 0.55–0.75; IRR: 0.86, 95% CI: 0.79–0.93) and glinide (HR: 0.47, 95% CI: 0.31–0.73; IRR: 0.84, 95% CI: 0.73–0.97) may lead to an increased frequency of within-day GV.ConclusionsAn increasing frequency of within-day GV was observed during the hospitalization in patients with type 2 diabetes, despite the effective reduction in the amplitude of within-day GV. Using medications designed to lower postprandial blood glucose could contribute to minimize the risk of frequent within-day GV.

Postprandial Glucose Excursions with Ultra-Rapid Insulin Analogs in Hybrid Closed-Loop Therapy for Adults with Type 1 Diabetes.

Objective: To evaluate postprandial glucose control when applying (1) faster-acting insulin aspart (Fiasp) compared to insulin aspart and (2) ultra-rapid insulin lispro (Lyumjev) compared to insulin lispro using the CamAPS FX hybrid closed-loop algorithm. Research Design and Methods: We undertook a secondary analysis of postprandial glucose excursions from two double-blind, randomized, crossover hybrid closed-loop studies contrasting Fiasp to standard insulin aspart, and Lyumjev to standard insulin lispro. Endpoints included incremental area under curve (iAUC)-2h, iAUC-4h, 4 h postprandial time in target range, time above range, and time below range. It was approved by independent research ethics committees. Results: Two trials with 8 weeks of data from 51 adults with type 1 diabetes were analyzed and 7137 eligible meals were included. During Lyumjev compared with insulin lispro, iAUC-2h and iAUC-4h were significantly decreased following breakfast (mean difference 92 mmol/L per 2 h (95% confidence interval [CI]: 56 to 127); P < 0.001 and 151 mmol/L per 4 h (95% CI: 74 to 229); P < 0.001, respectively) and the evening meal (P < 0.001 and P = 0.011, respectively). Mean time in target range (3.9-10.0 mmol/L) for 4 h postprandially significantly increased during Lyumjev with a mean difference of 6.7 percentage points (95% CI: 3.3 to 10) and 5.7 percentage points (95% CI: 1.4 to 9.9) for breakfast and evening meal, respectively. In contrast, there were no significant differences in iAUC-2h, iAUC-4h, and the other measures of postprandial glucose control between insulin aspart and Fiasp during breakfast, lunch, and evening meal (P > 0.05). Conclusion: The use of Lyumjev with CamAPS FX closed-loop system improved postprandial glucose excursions compared with insulin lispro, while the use of Fiasp did not provide any advantage compared with insulin aspart. Clinical Trial Registration numbers: NCT04055480, NCT05257460.

Glycemic Management Around Postprandial Exercise in People With Type 1 Diabetes: Challenge Accepted.

The precise glycemic impact and clinical relevance of postprandial exercise in type 1 diabetes (T1D) has not been clarified yet. This work aimed to examine acute, subacute, and late effects of postprandial exercise on blood glucose (BG). A randomized, controlled trial comprised 4 laboratory visits, with 24-hour follow-up at home. Participants included adults with T1D (n = 8), aged 44 ± 13 years, with body mass index of 24 ± 2.1. Intervention included 30 minutes of rest (CONTROL), walking (WALK), moderate-intensity (MOD), or intermittent high-intensity (IHE) exercise performed 60 minutes after a standardized meal. Main outcome measures included BG change during exercise/control (acute), and secondary outcomes included the subacute (≤2 h after) and late glycemic effects (≤24 h after). Exercise reduced postprandial glucose (PPG) excursion compared to CONTROL, with a consistent BG decline in all patients for all modalities (mean declines -45 ± 24, -71 ± 39, and -35 ± 21 mg/dL, during WALK, MOD, and IHE, respectively (P < .001). For this decline, clinical superiority was demonstrated separately for each exercise modality vs CONTROL. Noninferiority of WALK vs MOD was not demonstrated, noninferiority of WALK vs IHE was demonstrated, and equivalence of IHE vs MOD was not demonstrated. Hypoglycemia did not occur during exercise. BG increased in the hour after exercise (more than after CONTROL; P < .001). More than half of participants showed hyperglycemia after exercise necessitating insulin correction. There were more nocturnal hypoglycemic events after exercise vs CONTROL (P < .05). Postprandial exercise of all modalities is effective, safe, and feasible if necessary precautions are taken (ie, prandial insulin reductions), as exercise lowered maximal PPG excursion and caused a consistent and clinically relevant BG decline during exercise while there was no hypoglycemia during or shortly after exercise. However, there seem to be 2 remaining challenges: subacute postexercise hyperglycemia and nocturnal hypoglycemia.

Novel methodology to enrich medium- and short-chain fatty acids in milk fat to improve metabolic health.

Dietary short- and medium-chain fatty acids have been shown to elevate circulating ketone bodies and confer metabolic health benefits. Cow milk fat contains these lipids in a balanced mix but in relatively low concentrations. Enriching them could amplify health benefits of dairy products. Here, we used a volatility-based workflow to produce milk fat with a 2-fold enrichment of medium- and short-chain fatty acids (referred to as MSFAT). Our proof-of-concept studies in mice demonstrated that intake of MSFAT increased circulating ketone bodies, reduced blood glucose levels, and suppressed food intake. In humans, ingestion of MSFAT resulted in increased circulating ketone bodies, trended to attenuate (p = 0.07) postprandial glucose excursion, and acutely elevated energy expenditure. Our findings show that milk products enriched with MSFAT may hold significant metabolic advantages.

The Role of Ultra-Rapid-Acting Insulin Analogs in Diabetes: An Expert Consensus.

Ultra-rapid-acting insulin analogs (URAA) are a further development and refinement of rapid-acting insulin analogs. Because of their adapted formulation, URAA provide an even faster pharmacokinetics and thus an accelerated onset of insulin action than conventional rapid-acting insulin analogs, allowing for a more physiologic delivery of exogenously applied insulin. Clinical trials have confirmed the superiority of URAA in controlling postprandial glucose excursions, with a safety profile that is comparable to the rapid-acting insulins. Consequently, many individuals with diabetes mellitus may benefit from URAA in terms of prandial glycemic control. Unfortunately, there are only few available recommendations from authoritative sources for use of URAA in clinical practice. Therefore, this expert consensus report aims to define populations of people with diabetes mellitus for whom URAA may be beneficial and to provide health care professionals with concrete, practical recommendations on how best to use URAA in this context.

Effects of mulberry twig alkaloids(Sangzhi alkaloids) and metformin on blood glucose fluctuations in combination with premixed insulin-treated patients with type 2 diabetes.

We aimed to evaluated the effect of premixed insulin (Ins), premixed insulin combined with metformin (Ins+Met) or mulberry twig alkaloids(Ins+SZ-A) on blood glucose fluctuations in patients with type 2 diabetes (T2DM) using continuous glucose monitors (CGM). Thirty patients with T2DM and poor blood glucose control using drugs were evaluated for eligibility during the screening period. Subsequently, their original hypoglycemic drugs were discontinued during the lead-in period, and after receiving Ins intensive treatment for 2 weeks, they were randomly assigned to receive either Ins, Ins+Met, or Ins+SZ-A treatment for the following 12 weeks. The main efficacy endpoint comprised changes in their CGM indicators changes (mean blood glucose level [MBG], standard deviation of blood glucose [SDBG], mean amplitude of glycemic excursions [MAGE], postprandial glucose excursions [PPGE], the largest amplitude of glycemic excursions [LAGE], mean of daily difference [MODD], time in range between 3.9-10.0 mmol/L [TIR] and area under the curve for each meal [AUCpp]) during the screening, lead-in, and after 12-week treatment period. Changes in glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), 1-h postprandial blood glucose (1h-PBG), 2-h postprandial blood glucose (2h-PBG), fasting blood lipids and postprandial blood lipids were also measured at baseline and after 12 weeks of treatment. The CGM indicators of the three groups during the lead-in period all showed significant improvements compared to the screening period (P<0.05). Compared with those in the lead-in period, all of the CGM indicators improved in the the Ins+Met and Ins+SZ-A groups after 12 weeks of treatment (P<0.05), except for MODD. After 12-week treatment, compared with the Ins group, Ins+Met and Ins+SZ-A groups showed improved MBG, SDBG, TIR, breakfast AUCpp,lunch AUCpp, HbA1c, FBG, 1h-PBG, fasting blood lipid and postprandial blood lipid indicators (P<0.05). Further, the LAGE, PPGE, MAGE, dinner AUCpp and 2h-PBG levels of the Ins+SZ-A group were significantly lower than those of the Ins+Met and Ins groups (P<0.05). Our findings highlight the efficacy of combination therapy (Ins+SZ-A or Ins+Met) in improving blood glucose fluctuations, as well as blood glucose and lipid levels. Ins+SZ-A reduces postprandial blood glucose fluctuations more than Ins+Met and Ins groups. ISRCTN20835488.

Splitting Mealtime Insulin Doses for Mixed Fat and Protein Meals in Children and Adolescents with Type 1 Diabetes Using Multiple Daily Injection Regimen: A Randomized Cross-Over Trial

Aims. Assessment of the glycemic outcomes of increasing and splitting mealtime insulin doses for mixed fat and protein meals in pediatric patients with type 1 diabetes mellitus (T1DM) using multiple daily injection regimen and comparing the effects of regular insulin and fast-acting insulin on glycemic outcomes following those meals. Methods. This single-center, randomized, cross-over trial included 43 children and adolescents with T1DM randomly assigned to receive three interventional insulin doses for lunch meals over 3 consecutive days; Intervention A (100% insulin-to-carbohydrate ratio (ICR) dose given as premeal insulin lispro with an additional insulin sensitivity factor-calculated correction dose after 3 hr), Intervention B (130% ICR dose split into 60% premeal insulin lispro and 40% postmeal insulin lispro after 30 min), and Intervention C (130% ICR dose split into 60% premeal insulin lispro and 40% postmeal regular insulin after 30 min). The test meal consisted of two slices of pizza (weight: 150 g, carbohydrates: 40 g, fat: 15 g, protein: 20 g, and calories: 380 kcal). Postprandial blood glucose levels were monitored for 6 hr. Results. There were no significant differences in postprandial blood glucose excursions following the three interventions. However, Intervention C had a significantly lower late (3–6 hr) blood glucose area under the curve ( p = 0.01 ). Postprandial hypoglycemia developed in 12 participants (27.9%) following Interventions A and B and in 17 participants (39.5%) following Intervention C ( p = 0.32 ). Conclusions. Using regular insulin as a postmeal portion of increased and split insulin doses provided better late postprandial glycemic outcomes following mixed fat and protein meals. However, the amount of additional insulin used needs optimization to reduce the frequency of postprandial hypoglycemia. This trial is registered with NCT04783376.

Ultra-rapid lispro improved postprandial glucose control compared to insulin lispro in predominantly Chinese patients with type 1 diabetes: A prospective, randomized, double-blind phase 3 study.

To investigate the efficacy and safety of ultra-rapid lispro (URLi) versus insulin lispro in predominantly Chinese patients with type 1 diabetes (T1D) in a prospective, randomized, double-blind, treat-to-target, phase 3 study. Following a lead-in period, during which insulin glargine U-100 or insulin degludec U-100 was optimized, patients were randomly assigned (1:1) to URLi (n = 176) or insulin lispro (n = 178). The primary objective was to test the noninferiority of URLi to insulin lispro in glycaemic control (noninferiority margin = 0.4% for glycated haemoglobin [HbA1c] change from baseline to week 26), with testing for the superiority of URLi to insulin lispro with regard to 1- and 2-hour postprandial glucose (PPG) excursions during a mixed-meal tolerance test and HbA1c change at week 26 as the multiplicity-adjusted objectives. From baseline to week 26, HbA1c decreased by 0.21% and 0.28% with URLi and insulin lispro, respectively, with a least squares mean treatment difference of 0.07% (95% confidence interval -0.11 to 0.24; P = 0.467). URLi demonstrated smaller 1- and 2-hour PPG excursions at week 26 with least squares mean treatment differences of -1.0 mmol/L (-17.8 mg/dL)and -1.4 mmol/L (-25.5 mg/dL), respectively (p < 0.005 for both) versus insulin lispro. The safety profiles of URLi and insulin lispro were similar. In this study, URLi administered in a basal-bolus regimen demonstrated superiority to insulin lispro in controlling PPG excursions, with noninferiority of HbA1c control in predominantly Chinese patients with T1D.