Glycemic Effects Research Articles

Understanding Metabolic Memory: A Tale of Two Studies.

The results of the Diabetes Control and Complications Trial (DCCT) have given rise to much encouragement in the battle to stave off the complications of type 1 diabetes, showing dramatic declines in the development of severe retinopathy, nephropathy, and neuropathy in those treated intensively compared with conventional therapy. Particularly encouraging has been the continuing difference between the two groups despite both having similar HbA1c (∼8%) since the end of DCCT, when 96% of participants entered the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. This continuing relative benefit has been termed "metabolic memory," which implies altered metabolic regulation. Based on evidence from both the Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset type 1 diabetes and DCCT/EDIC, we show that the metabolic memory effect can be largely explained by lower cumulative glycemic exposure in the intensive therapy group, and, on average, the development of complications increases with greater glycemic exposure, irrespective of whether this results from a high exposure for a short time or a lower exposure for a longer time. Thus, there is no need for a concept like "metabolic memory" to explain these observations. Potential mechanisms explaining the cumulative glycemic effect are also briefly discussed.

Favorable pleiotropic effects of sodium glucose cotransporter 2 inhibitors: head-to-head comparisons with dipeptidyl peptidase-4 inhibitors in type 2 diabetes patients

BackgroundSodium glucose cotransporter 2 (SGLT2) inhibitors have shown greater reductions of cardiovascular event risks than dipeptidyl peptidase-4 (DPP4) inhibitors, whereby possible mechanisms may involve the better pleiotropic effects of SGLT2 inhibitors. However, no published data are currently available to directly compare glycemic and pleiotropic effects in real-world type 2 diabetes patients initiating SGLT2 inhibitors or DPP4 inhibitors.MethodWe conducted a retrospective cohort study by analyzing the Chang Gung Research Database, the largest multi-institutional electronic medical records database in Taiwan. We included patients newly receiving SGLT2 inhibitor or DPP4 inhibitor intensification therapy for type 2 diabetes from 2016 to 2017. We matched SGLT2 inhibitor users to DPP4 inhibitor users (1:4) by propensity scores to ensure comparable characteristics between the groups. We primarily evaluated 1-year post-treatment changes of hemoglobin A1c (HbA1c) after SGLT2 inhibitor or DPP4 inhibitor initiation, using two-tailed independent t-test. We also evaluated post-treatment changes in body weight, systolic blood pressure (SBP), alanine aminotransferase (ALT) and estimated glomerular filtration rate (eGFR) values, associated with SGLT2 inhibitors and DPP4 inhibitors.ResultsWe identified a cohort of 2028 SGLT2 inhibitors and 8112 matched DPP4 inhibitors new users. SGLT2 inhibitors and DPP4 inhibitors showed similar HbA1c reductions (− 1.0 vs. − 1.1%; P = 0.076), but patients receiving SGLT2 inhibitors had greater improvements in body weight (− 1.5 vs. − 1.0 kg; P = 0.008), SBP (− 2.5 vs. − 0.7 mmHg; P < 0.001) and ALT values (− 4.1 vs. − 0.0 U/l; P < 0.001) and smaller declines in eGFR values (− 2.0 vs. − 3.5 ml/min/1.73 m2; P < 0.001) when compared to DPP4 inhibitors.ConclusionSGLT2 inhibitors had glucose-lowering effects comparable to those of DPP4 inhibitors but more favorable pleiotropic effects on body weight, ALT and eGFR changes, potentially improving type 2 diabetes patients’ cardio-metabolic disease risks.

The Effects of Perioperative Dexamethasone on Glycemic Control and Postoperative Outcomes

Objective: Perioperative glucocorticoids are commonly given to reduce pain and nausea in patients undergoing surgery. However, the glycemic effects of steroids and the potential effects on morbidity and mortality have not been systematically evaluated. This study investigated the association between perioperative dexamethasone and postoperative blood glucose, hospital length of stay (LOS), readmission rates, and 90-day survival. Methods: Data from 4,800 consecutive orthopedic surgery patients who underwent surgery between 2000 and 2016 within a single health system were analyzed retrospectively. Results: Patients with and without diabetes mellitus (DM) who were given a single dose of dexamethasone had higher rates of hyperglycemia during the first 24 hours after surgery as compared to those who did not receive dexamethasone (hazard ratio [HR] was 1.81, and 95% confidence interval [CI] was [1.46, 2.24] for the DM cohort; HR 2.34, 95% CI [1.66, 3.29] for the nonDM cohort). LOS was nearly 1 day shorter in patients who received dexamethasone (geometric mean ratio [GMR] 0.79, 95% CI [0.75, 0.83] for patients with DM; GMR 0.75, 95% CI [0.72, 0.79] for patients without DM), and there was no difference in 90-day readmission rates. In patients without DM, dexamethasone was associated with a higher 90-day overall survival (99.07% versus 96.90%; P = .004). Conclusion: In patients with and without DM who undergo orthopedic surgery, perioperative dexamethasone was associated with a transiently higher risk of hyperglycemia. However, dexamethasone treatment was associated with a shorter LOS in patients with and without DM, and a higher overall 90-day survival rate in patients without DM, compared to patients who did not receive dexamethasone. Abbreviations: BMI = body mass index; CAD = coronary artery disease; CI = confidence interval; DM = diabetes mellitus; GMR = geometric mean ratio; HR = hazard ratio; IV = intravenous; LOS = length of stay; POD = postoperative day.

Alpha-Cyclodextrin Attenuates the Glycemic and Insulinemic Impact of White Bread in Healthy Male Volunteers.

The demonstration of a physiological benefit has recently become an indispensible element of the definition of dietary fibers. In the here-reported pilot study, the effect of alpha-cyclodextrin (alpha-CD) on the postprandial glycemic and insulinemic effect of starch was examined. Twelve fasted, healthy male volunteers received, on three subsequent days, a test breakfast consisting of (A) 100 g fresh white bread (providing 50 g starch) and 250 mL drinking water, (B) the same bread with a supplement of 10 g alpha-CD dissolved in the drinking water, and (C) 25 g alpha-CD dissolved in drinking water. Capillary and venous blood was sampled before the breakfast and in regular intervals for a three-hour period thereafter. Glucose was determined in capillary blood and insulin in the plasma of venous blood samples. Breakfast (A) led to a rapid rise in blood glucose and insulin. In breakfast (B), alpha-CD reduced the areas under the curve of blood glucose and insulin significantly by 59% and 57%, respectively, demonstrating that alpha-CD inhibits and thereby delays starch digestion. Treatment (C) was not associated with a rise of blood glucose. Hence, alpha-CD complies with the current definition of dietary fiber in every respect.

Renal physiology of glucose handling and therapeutic implications.

The rationale for using sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) has evolved over the last decade. Due to the effects on glucosuria and body weight loss, SGLT2 inhibitors were originally approved for glycemic control in T2D. Since glucosuria is attenuated in chronic kidney disease (CKD) Stages 3–5, initial regulatory approval for SGLT2 inhibitor use was limited to patients with T2D and preserved estimated glomerular filtration rate. Over time, however, it has become increasingly apparent that these therapies have a variety of important pharmacodynamic and clinical effects beyond glycemic lowering, including antihypertensive and antialbuminuric properties, and the ability to reduce glomerular hypertension. Importantly, these sodium-related effects are preserved across CKD stages, despite attenuated glycemic effects, which are lost at CKD Stage 4. With the completion of cardiovascular (CV) outcome safety trials—EMPA-REG OUTCOME, CANVAS Program and DECLARE TIMI-58—in addition to reductions in CV events, SGLT2 inhibition consistently reduces hard renal endpoints. Importantly, these CV and renal effects are independent of glycemic control. Subsequent data from the recent CREDENCE trial—the first dedicated renal protection trial with SGLT-2 inhibition—demonstrated renal and CV benefits in albuminuric T2D patients, pivotal results that have expanded the clinical importance of these therapies. Ongoing trials will ultimately determine whether SGLT2 inhibition will have a role in renal protection in other clinical settings, including nondiabetic CKD and type 1 diabetes.

SGLT inhibitors in type 1 diabetes: weighing efficacy and side effects.

Even before sodium-glucose cotransporter inhibitors (SGLTi) became popular agents for the treatment of people with type 2 diabetes (T2DM), clinicians had explored their potential as adjunct therapies in type 1 diabetes (T1DM). Several trials have demonstrated improved glycemic control (compared with placebo) and a decrease in glucose variability with a clinically relevant increase of time in range. In addition, weight loss and decreased systolic blood pressure are observed. The magnitude of the effects observed depends on the type of SGLTi, the dose administrated, and the duration of observation in the studies. As seen in T2DM, there was an increase in the risk of urogenital mycotic infections, but no increase in the risk of severe hypoglycemia. However, concerns arose regarding an increase in incidence of diabetic ketoacidosis. Mitigation strategies, including careful patient selection, extensive education of patients and (para)medical personnel, adequate insulin dose titration, and the adoption of a ketone-centered approach, are suggested.In different areas of the world, SGLTi are approved for use in T1DM with restrictions concerning patient selection and SGLTi dose. Real-world data on the effect of introduction of SGLTi in people with T1DM will yield insight on the robustness of glycemic effects over time, and allow us to determine whether the positive risk–benefit profile observed in clinical trials can be translated to the real world.

Ingestion of isomalto-oligosaccharides stimulates insulin and incretin hormone secretion in healthy adults

Abstract The postprandial blood glucose and hormonal responses to isomalto-oligosaccharides (IMO) are unclear. The objective of this study was to compare postprandial glucose, insulin and incretin responses of IMO with dextrose in healthy adults. In trial 1, blood glucose responses to IMO, isomaltose, dextran and maltodextrin were compared with dextrose in n = 12 participants. In trial 2, serial glucose and hormone measurements over 2 h were measured in n = 10 participants. The glycemic effect of IMO was calculated using the Glycemic Glucose Equivalents (GGE) and Relative Glycemic Index (RGI). IMO exhibited a hyperglycemic effect compared to dextrose as indicated by a GGE of 1.35 g and an RGI of 27.0 g. The responses to IMO of both active GLP-1 and GIP were similar to that of dextrose. The paradoxical hyperglycemic response despite robust insulin and incretin secretion requires further investigation.

Insulin Dosing for Fat and Protein: Is it Time?

The impact of dietary fat and protein on postprandial glycemia in type 1 diabetes (T1D) and the need to adjust for them in the mealtime insulin dose have been controversial (1,2). Recently, carefully designed randomized trials in individuals living with T1D have shown protein and fat consumed in meals with carbohydrate reduce the early postprandial rise (1–2 h) and contribute to postprandial hyperglycemia in the late (3–6 h) postprandial period (3–5). In clinical practice, continuous glucose monitoring highlights the glycemic effects of different meal types demonstrating that mealtime insulin dosing strategies based on carbohydrate counting alone have limitations. There is a need for an evidence-based, safe, and practical method to guide insulin adjustments for high-fat, high-protein meals. In this issue of Diabetes Care , Bell et al. (6) address the pressing clinical question of optimal insulin adjustments for meals containing differing amounts of dietary fat. This is important because postprandial hyperglycemia has been identified as a risk factor for the development of long-term complications of diabetes (7), and higher fat diets have increased in popularity in recent years. The mechanisms by which all three macronutrients impact blood glucose levels in people with T1D is shown in Fig. 1. Dietary carbohydrate is absorbed and rapidly increases the blood glucose concentration (8). Dietary protein results in a delayed and more prolonged increase in blood glucose levels by conversion of amino acids to glucose through gluconeogenesis, as well as an influence on multiple hormones including glucagon, cortisol, growth hormone, insulin-like growth factor 1, and ghrelin, thus increasing insulin resistance (9). Dietary fat also results in a delayed glycemic response by a number of mechanisms. Free fatty acids act via peroxisome proliferator–activated receptors and free fatty acid receptors to impact …

Cardiovascular effects of glucagon-like peptide 1 receptor agonists: from mechanistic studies in humans to clinical outcomes.

Type 2 diabetes mellitus (T2DM) is currently one of the most prevalent diseases, with as many as 415 million patients worldwide. T2DM is characterized by elevated blood glucose levels and is often accompanied by several comorbidities, such as cardiovascular disease. Treatment of T2DM is focused on reducing glucose levels by either lifestyle changes or medical treatment. One treatment option for T2DM is based on the gut-derived hormone glucagon-like peptide 1 (GLP-1). GLP-1 reduces blood glucose levels by stimulating insulin secretion, however, it is rapidly degraded, and thereby losing its glycaemic effect. GLP-1 receptor agonists (GLP-1RAs) are immune to degradation, prolonging the glycaemic effect. Lately, GLP-1RAs have spiked the interest of researchers and clinicians due to their beneficial effects on cardiovascular disease. Preclinical and clinical data have demonstrated that GLP-1 receptors are abundantly present in the heart and that stimulation of these receptors by GLP-1 has several effects. In this review, we will discuss the effects of GLP-1RA on heart rate, blood pressure, microvascular function, lipids, and inflammation, as measured in human mechanistic studies, and suggest how these effects may translate into the improved cardiovascular outcomes as demonstrated in several trials.

Executive task-based brain function in children with type 1 diabetes: An observational study.

BackgroundOptimal glycemic control is particularly difficult to achieve in children and adolescents with type 1 diabetes (T1D), yet the influence of dysglycemia on the developing brain remains poorly understood.Methods and findingsUsing a large multi-site study framework, we investigated activation patterns using functional magnetic resonance imaging (fMRI) in 93 children with T1D (mean age 11.5 ± 1.8 years; 45.2% female) and 57 non-diabetic (control) children (mean age 11.8 ± 1.5 years; 50.9% female) as they performed an executive function paradigm, the go/no-go task. Children underwent scanning and cognitive and clinical assessment at 1 of 5 different sites. Group differences in activation occurring during the contrast of “no-go > go” were examined while controlling for age, sex, and scan site. Results indicated that, despite equivalent task performance between the 2 groups, children with T1D exhibited increased activation in executive control regions (e.g., dorsolateral prefrontal and supramarginal gyri; p = 0.010) and reduced suppression of activation in the posterior node of the default mode network (DMN; p = 0.006). Secondary analyses indicated associations between activation patterns and behavior and clinical disease course. Greater hyperactivation in executive control regions in the T1D group was correlated with improved task performance (as indexed by shorter response times to correct “go” trials; r = −0.36, 95% CI −0.53 to −0.16, p < 0.001) and with better parent-reported measures of executive functioning (r values < −0.29, 95% CIs −0.47 to −0.08, p-values < 0.007). Increased deficits in deactivation of the posterior DMN in the T1D group were correlated with an earlier age of T1D onset (r = −0.22, 95% CI −0.41 to −0.02, p = 0.033). Finally, exploratory analyses indicated that among children with T1D (but not control children), more severe impairments in deactivation of the DMN were associated with greater increases in hyperactivation of executive control regions (T1D: r = 0.284, 95% CI 0.08 to 0.46, p = 0.006; control: r = 0.108, 95% CI −0.16 to 0.36, p = 0.423). A limitation to this study involves glycemic effects on brain function; because blood glucose was not clamped prior to or during scanning, future studies are needed to assess the influence of acute versus chronic dysglycemia on our reported findings. In addition, the mechanisms underlying T1D-associated alterations in activation are unknown.ConclusionsThese data indicate that increased recruitment of executive control areas in pediatric T1D may act to offset diabetes-related impairments in the DMN, ultimately facilitating cognitive and behavioral performance levels that are equivalent to that of non-diabetic controls. Future studies that examine whether these patterns change as a function of improved glycemic control are warranted.

Apple Preload Halved the Postprandial Glycaemic Response of Rice Meal on in Healthy Subjects.

This study aimed to investigate the possible glycemic effect of apple preload on acute postprandial glycemic responses (GRs) of a following rice meal, comparing with its co-ingestion counterpart and an apple sugar solution preload, based on equal carbohydrates intake. In a randomized crossover trial, 18 healthy female subjects consumed (1) rice, (2) co-ingestion of apple and rice (A+R), (3) apple preload and rice (PA+R), and (4) rice with sugar solution preload (same sugar profile as in apple) (PSS+R). Acute postprandial GR tests and subjective satiety tests were carried out for each test food. Compared with rice reference, the PA+R achieved a 50% reduction of the iAUC0-120, a 51.4% reduction of the average peak value, and a 52.6% reduction of glycemic excursion in 240 min, while the PSS+R showed 29.7% and 31.6% reduction of peak value and glycemic excursion, respectively. No significant differences were found between R and PA+R in any of the satiety characteristics. Compared with rice control, apple preload of 15 g available carbohydrates remarkably lowered the acute postprandial GR without negative effect on satiety. The sugar component may partly contribute to the glycemic suppressing effect of the apple preload.

Oral Semaglutide In The Management Of Type 2 Diabetes: A Report On The Evidence To Date.

In recent years, newer drug classes for the treatment of type 2 diabetes mellitus have been released with significant effects on glucose lowering and weight reduction. One of the most promising classes in achieving these goals has been the glucagon-like peptide (GLP)-1 agonists. However, a difficulty with the use of these agents is the need for subcutaneous injections, which can be inconvenient to individuals living with type 2 diabetes. More recently, a GLP-1 agonist has been developed, semaglutide, that can be administered orally which has at least similar effects to the subcutaneous preparation from which this compound is derived. In this review article, we discuss the glycemic and cardiovascular effects of the GLP-1 agonists with special emphasis on oral semaglutide and the potential role of this therapy in individuals with type 2 diabetes.

DR10601, a novel recombinant long-acting dual glucagon-like peptide-1 and glucagon receptor agonist for the treatment of obesity and type 2 diabetes mellitus.

Both glucagon-like peptide-1 (GLP-1) and glucagon (GCG) belong to the incretin family. This study aimed to investigate the pharmacokinetics and pharmacodynamics of DR10601, a fully recombinant hybrid peptide with dual GLP-1/GCG receptor agonistic activity. The agonistic ability of DR10601 was indirectly assessed by inducing cAMP accumulation in Chinese hamster ovary cells transfected with GLP-1R or GCGR in vitro. Following s.c. administration, the plasma pharmacokinetics of DR10601 were analysed in male Sprague-Dawley rats. The antiobesity effects and improved glycaemic control of DR10601 in vivo were evaluated by administering DR10601 to high-fat DIO mice and ICR mice as a single dose or repeated s.c. doses once every 4days for 24days. DR10601 exhibits dual agonistic activity on GLP-1 and glucagon receptors. The plasma half-life of DR10601 in Sprague-Dawley rats following s.c. administration was 51.9 ± 12.2h. In an IPGTT, a single s.c. dose of DR10601 (30nmol/kg) produced similar glycaemic control effects and a longer duration of action compared to dulaglutide (10nmol/kg). Compared with that achieved with liraglutide (40nmol/kg) s.c. administered daily, DR10601 administered s.c. once every 4days at 90nmol/kg exerted a nearly equivalent effect on food intake and significantly reduced the body weights of high-fat DIO mice at 24days. Repeated administration of DR1060 provides potent and sustained glycemic control and body weight loss effect in high-fat DIO mice. DR10601 is a promising long-acting agent deserving further investigation for the treatment of type 2 diabetes and obesity.

Obesity Does Not Modulate the Glycometabolic Benefit of Insoluble Cereal Fibre in Subjects with Prediabetes-A Stratified Post Hoc Analysis of the Optimal Fibre Trial (OptiFiT).

Obesity does not modulate the glycometabolic benefit of insoluble cereal fibre in subjects with prediabetes—a stratified post hoc analysis of the Optimal Fibre Trial (OptiFiT). Background: OptiFiT demonstrated the beneficial effect of insoluble oat fibres on dysglycemia in prediabetes. Recent analyses of OptiFiT and other randomised controlled trials (RCTs) indicated that this effect might be specific for the subgroup of patients with impaired fasting glucose (IFG). As subjects with IFG are more often obese, there is a need to clarify if the effect modulation is actually driven by glycemic state or body mass index (BMI). Aim: We conducted a stratified post hoc analysis of OptiFiT based on the presence or absence of obesity. Methods: 180 Caucasian participants with impaired glucose tolerance (IGT) were randomised in a double-blinded fashion to either twice-a-day fibre or placebo supplementation for 2 years (n = 89 and 91, respectively). Once a year, they underwent fasting blood sampling, an oral glucose tolerance test (oGTT) and full anthropometry. At baseline, out of 136 subjects who completed the first year of intervention, 87 (62%) were classified as OBESE (BMI >30) and 49 subjects were NONOBESE. We performed a stratified per-protocol analysis of the primary glycemic and secondary metabolic effects attributable to dietary fibre supplementation after 1 year of intervention. Results: Neither the NONOBESE nor the OBESE subgroup showed significant differences between the respective fibre and placebo groups in metabolic, anthropometric or inflammatory outcomes. None of the four subgroups showed a significant improvement in either fasting glucose or glycated haemoglobin (HbA1c) after 1 year of intervention and only OBESE fibre subjects improved 2 h glucose. Within the NONOBESE stratum, there were no significant differences in the change of primary or secondary metabolic parameters between the fibre and placebo arms. We found a significant interaction effect for leukocyte count (time × supplement × obesity status). Within the OBESE stratum, leukocyte count and gamma-glutamyl transferase (GGT) levels decreased more in the fibre group compared with placebo (adjusted for change in body weight). Comparison of both fibre groups revealed that OBESE subjects had a significantly stronger benefit with respect to leukocyte count and fasting C-peptide levels than NONOBESE participants. Only the effect on leukocyte count survived correction for multiple comparisons. In contrast, under placebo conditions, NONOBESE subjects managed to decrease their body fat content significantly more than OBESE ones. Intention-to-treat (ITT) analysis resulted in similar outcomes. Conclusions: The state of obesity does not relevantly modulate the beneficial effect of cereal fibre on major glycometabolic parameters by fibre supplementation, but leukocyte levels may be affected. Hence, BMI is not a suitable parameter to stratify this cohort with respect to diabetes risk or responsiveness to cereal fibre, but obesity needs to be accounted for when assessing anti-inflammatory effects of fibre treatments. Targeted diabetes prevention should focus on the actual metabolic state rather than on mere obesity.

Glycemic control influences on academic performance in youth with Type 1 diabetes.

This study examined how children's and adolescents' with Type 1 diabetes mellitus glucose levels during and prior to academic assessment contributed to performance on reading, writing, and mathematics tasks. Participants had a mean age of 13.69 (SD = 2.10); 44.6% were female and 58.1% reported their ethnicity to be Hispanic, Latino, or Mexican. They wore a continuous glucose monitor for approximately 6 days and completed a neurobehavioral evaluation that consisted of tasks assessing basic reading skills, reading fluency, reading comprehension, math fact fluency, math calculation, spelling, and writing fluency. Results indicated that individuals whose glucose levels were suboptimal (>140 mg/dL) or hyperglycemic (>180 mg/dL) had significantly lower scores on reading fluency (ηp2 = .16) and writing fluency (ηp2 = .28) subtests than those in the target range (70-140 mg/dL). Moreover, more time spent hypoglycemic (<70 mg/dL) within the 12 hr prior to the evaluation increased the risk for impaired performance on academic tasks. These findings support the need to move beyond considering only overall glycemic control to review temporal influences of glucose levels on academic performance. By tracking how fluctuations impact academic performance, school based practitioners can better determine necessary accommodations to buffer glycemic dysregulation effects. In particular, individuals whose glucose levels are frequently outside of the target range are at greatest risk for performing below their true academic potential. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Effect of the Glucagon-like Peptide-1 Mimetic on Ion- and Osmoregulating Renal Functions in Normoglycemia and Hyperglycemia

Incretins are hormones with a wide range of biological activity. We studied the ratio of the glycemic effect of the glucagon-like peptide-1 mimetic and its effect on the renal excretion of sodium and water. It was found that both effects depend on the initial blood concentration of glucose. In normoglycemia, exenatide had no effect on blood sugar level, but it significantly increased urinary sodium excretion and reabsorption of solute-free water. In hyperglycemia the blood glucose concentration was normalized by exenatide, while the excretion of sodium by the kidneys and the reabsorption of solute-free water were increased to a small extent. This pattern was found both in patients with type 2 diabetes mellitus and in rats with hyperglycemia induced by intraperitoneal injection of glucose.

Glycemic effect of pancreatic preproglucagon in mouse sleeve gastrectomy.

Intestinally derived glucagon-like peptide-1 (GLP-1), encoded by the preproglucagon (Gcg) gene, is believed to function as an incretin. However, our previous work questioned this dogma and demonstrated that pancreatic peptides rather than intestinal Gcg peptides, including GLP-1, are a primary regulator of glucose homeostasis in normal mice. The objective of these experiments was to determine whether changes in nutrition or alteration of gut hormone secretion by bariatric surgery would result in a larger role for intestinal GLP-1 in the regulation of insulin secretion and glucose homeostasis. Multiple transgenic models, including mouse models with intestine- or pancreas tissue-specific Gcg expression and a whole-body Gcg-null mouse model, were generated to study the role of organ-specific GLP-1 production on glucose homeostasis under dietary-induced obesity and after weight loss from bariatric surgery (vertical sleeve gastrectomy; VSG). Our findings indicated that the intestine is a major source of circulating GLP-1 after various nutrient and surgical stimuli. However, even with the 4-fold increase in intestinally derived GLP-1 with VSG, it is pancreatic peptides, not intestinal Gcg peptides, that are necessary for surgery-induced improvements in glucose homeostasis.

Impact of dietary protein on postprandial glycaemic control and insulin requirements in Type 1 diabetes: a systematic review.

Postprandial hyperglycaemia is a challenge for people living with Type 1 diabetes. In addition to carbohydrate, dietary protein has been shown to contribute to postprandial glycaemic excursions with recommendations to consider protein when calculating mealtime insulin doses. The aim of this review is to identify and synthesize evidence about the glycaemic impact of dietary protein and insulin requirements for individuals with Type 1 diabetes. A systematic literature search of relevant biomedical databases was performed to identify research on the glycaemic impact of dietary protein when consumed alone, and in combination with other macronutrients in individuals with Type 1 diabetes. The review included 14 published studies dated from 1992 to 2018, and included studies that researched the impact of protein alone (n=2) and protein in a mixed meal (n=12). When protein was consumed alone a glycaemic effect was not seen until ≥75g. In a carbohydrate-containing meal ≥12.5g of protein impacted the postprandial glucose. Inclusion of fat in a high-protein meal enhanced the glycaemic response and further increased insulin requirements. The timing of the glycaemic effect from dietary protein ranged from 90 to 240min. Studies indicate that the postprandial glycaemic response and insulin requirements for protein are different when protein is consumed alone or with carbohydrate and/or fat. This systematic review provides evidence that dietary protein contributes to postprandial glycaemic excursions and insulin requirements. These insights have important implications for the education of people with Type 1 diabetes and highlights the need for more effective insulin dosing strategies for mixed macronutrient meals.

Postprandial Glycemic and Insulinemic Effects of the Addition of Aqueous Extracts of Dried Corn Silk, Cumin Seed Powder or Tamarind Pulp, in Two Forms, Consumed with High Glycemic Index Rice.

Several plant-based traditional ingredients in Asia are anecdotally used for preventing and/or treating type 2 diabetes. We investigated three such widely consumed ingredients, namely corn silk (CS), cumin (CU), and tamarind (TA). The aim of the study was to determine the effects of aqueous extracts of these ingredients consumed either as a drink (D) with high-glycemic-index rice or added to the same amount of rice during cooking (R) on postprandial glycemia (PPG), insulinemia (PPI), and blood pressure (BP), over a 3 h measurement period. Eighteen healthy Chinese men (aged 37.5 ± 12.5 years, BMI 21.8 ± 1.67 kg/m2) took part in a randomized crossover trial, each completing up to nine sessions. Compared to the control meal (plain rice + plain water), the addition of test extracts in either form did not modulate PPG, PPI, or BP. However, the extracts when added within rice while cooking gave rise to significantly lower PPI than when consumed as a drink (p < 0.01). Therefore, the form of consumption of phytochemical-rich ingredients can differentially modulate glucose homeostasis. This study also highlights the need for undertaking randomized controlled clinical trials with traditional foods/components before claims are made on their specific health effects.

The Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors: Beyond the Glycemic Benefit.

Type 2 diabetes (T2D) is associated with an increased risk of macro- and microvascular complications, including cardiovascular disease (CVD), heart failure (HF), and chronic kidney disease (CKD). Of the currently available glucose-lowering therapies, sodium–glucose cotransporter-2 inhibitors (SGLT-2is) are the only class to target the pathophysiologic increase in renal glucose reabsorption in patients with T2D. In CV outcomes trials of SGLT-2is in patients with T2D and established CVD or varying levels of CV risk, empagliflozin, canagliflozin, and dapagliflozin were associated with significant improvements in the risk of composite CV and renal outcomes compared with placebo that extended beyond their glycemic effects. Real-world observational studies have also reported improvements in CV outcomes with SGLT-2is compared with other glucose-lowering therapy in routine clinical practice. This review describes the pleiotropic effects of SGLT-2is and discusses the potential mechanisms for these effects as well as how they potentially provide benefits beyond glycemic control in patients with T2D. These favorable nonglycemic effects indicate that SGLT-2is may be of particular benefit in patients with diabetic complications, such as CVD, HF, or CKD. Ongoing large randomized trials in specific patient populations, including those with CVD, HF, or CKD (with or without T2D), may help to confirm the benefits of SGLT-2is in these patients and further elucidate the potential mechanisms of their pleiotropic effects.FundingAstraZeneca.