Improved Glucose Control Research Articles

Intervention Enhancement Strategies Among Adults With Type 2 Diabetes in a Very Low–Carbohydrate Web-Based Program: Evaluating the Impact With a Randomized Trial

BackgroundAdults with type 2 diabetes may experience health benefits, including glycemic control and weight loss, from following a very low–carbohydrate, ketogenic (VLC) diet. However, it is unclear which ancillary strategies may enhance these effects.ObjectiveThis pilot study aims to estimate the effect sizes of 3 intervention enhancement strategies (text messages, gifts, and breath vs urine ketone self-monitoring) that may improve outcomes of a 12-month web-based ad libitum VLC diet and lifestyle intervention for adults with type 2 diabetes. The primary intervention also included other components to improve adherence and well-being, including positive affect and mindfulness as well as coaching.MethodsOverweight or obese adults (n=44; BMI 25-45 kg/m2) with type 2 diabetes (glycated hemoglobin [HbA1c] ≥6.5%), who had been prescribed either no glucose-lowering medications or metformin alone, participated in a 12-month web-based intervention. Using a 2×2×2 randomized factorial design, we compared 3 enhancement strategies: (1) near-daily text messages about the intervention’s recommended behaviors (texts n=22 vs no texts n=22), (2) mailed gifts of diet-relevant foods and cookbooks (6 rounds of mailed gifts n=21 vs no gifts n=23), and (3) urine- or breath-based ketone self-monitoring (urine n=21 vs breath n=23). We assessed HbA1c and weight at baseline and at 4, 8, and 12 months. We evaluated whether each strategy exerted a differential impact on HbA1c and weight at 12 months against an a priori threshold of Cohen d of 0.5 or greater.ResultsWe retained 73% (32/44) of the participants at 12 months. The intervention, across all conditions, led to improvements in glucose control and reductions in body weight at the 12-month follow-up. In intent-to-treat (ITT) analyses, the mean HbA1c reduction was 1.0% (SD 1.6) and the mean weight reduction was 5.3% (SD 6.0), whereas among study completers, these reductions were 1.2% (SD 1.7) and 6.3% (SD 6.4), respectively, all with a P value of less than .001. In ITT analyses, no enhancement strategy met the effect size threshold. Considering only study completers, 2 strategies showed a differential effect size of at least a d value of 0.5 or greaterConclusionsText messages, gifts of food and cookbooks, and urine-based ketone self-monitoring may potentially enhance the glycemic or weight loss benefits of a web-based VLC diet and lifestyle intervention for individuals with type 2 diabetes. Future research could investigate other enhancement strategies to help create even more effective solutions for the treatment of type 2 diabetes.Trial RegistrationClinicalTrials.gov NCT02676648; http://clinicaltrials.gov/ct2/show/NCT02676648

Walking for subjects with type 2 diabetes: A systematic review and joint AMD/SID/SISMES evidence-based practical guideline

AimsRegular exercise is considered a cornerstone in the management of type 2 diabetes mellitus (T2DM). It improves glucose control and cardiovascular risk factors, contributes to weight loss, and also improves general well-being, likely playing a role in the prevention of chronic complications of diabetes. However, compliance to exercise recommendations is generally inadequate in subjects with T2DM. Walking is the most ancestral form of physical activity in humans, easily applicable in daily life. It may represent, in many patients, a first simple step towards lifestyle changes. Nevertheless, while most diabetic patients do not engage in any weekly walking, exercise guidelines do not generally detail how to improve its use. The aims of this document are to conduct a systematic review of available literature on walking as a therapeutic tool for people with T2DM, and to provide practical, evidence-based clinical recommendations regarding its utilization in these subjects. Data synthesisAnalysis of available RCTs proved that regular walking training, especially when supervised, improves glucose control in subjects with T2DM, with favorable effects also on cardiorespiratory fitness, body weight and blood pressure. Moreover, some recent studies have shown that even short bouts of walking, used for breaking prolonged sitting, can ameliorate glucose profiles in diabetic patients with sedentary behavior. ConclusionsThere is sufficient evidence to recognize that walking is a useful therapeutic tool for people with T2DM. This document discusses theoretical and practical issues for improving its use.This article is co-published in the journals Sport Sciences for Health and Nutrition, Metabolism and Cardiovascular Diseases.

Organoids control glucose

Human islet-like organoids improve glucose control in immunocompetent mice.

Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes.

What is known and objectiveIn recent years, glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) including once‐weekly (QW) formulations have been incorporated into type 2 diabetes (T2D) clinical guidelines, making it essential that pharmacists and healthcare professionals (HCPs) have a clear understanding of their safety profiles. Currently, three QW GLP‐1 RAs are approved and marketed in the United States for the treatment of T2D: dulaglutide, exenatide extended‐release and semaglutide. This review provides pharmacists and HCPs with collated data related to potential safety and tolerability issues when patients use QW GLP‐1 RAs, enabling patient education and treatment optimization.MethodsThis is a narrative review comparing the safety and tolerability of the three QW GLP‐1 RAs, using data from Phase 3 clinical trials. Extracted safety data included gastrointestinal (GI) adverse events (AEs), hypoglycaemia, injection‐site reactions, pancreatitis, neoplasms, gallbladder events, and diabetic retinopathy (DR) and/or its complications (DRCs).Results and discussionA total of 30 trials were identified for inclusion; eight were head‐to‐head trials involving another GLP‐1 RA; of these, six compared GLP‐1 RAs with different dosing regimens (QW vs once‐daily or twice‐daily), and two were direct QW vs QW GLP‐1 RA comparisons. The most commonly reported AEs were GI events (notably nausea, vomiting and diarrhoea), but there was variation between the three QW drugs. These were generally mild‐to‐moderate in severity and transient. Risk of hypoglycaemia, injection‐site reactions, pancreatitis, neoplasms and gallbladder events was generally low across the GLP‐1 RAs investigated. Overall rates of DR or DRC were low across the trials. Only in one trial (SUSTAIN 6) there were significantly more DRC events reported in patients treated with QW semaglutide (3.0%) compared with placebo (1.8%). This was likely due to the rapid improvement in glucose control in patients with pre‐existing DR enrolled within that trial.What is new and conclusionThis review puts the latest clinical data from the marketed QW GLP‐1 RAs into context with results from older Phase 3 trials, to enable pharmacists and HCPs to make informed treatment decisions. Each of the three QW GLP‐1 RAs has their own safety profile, which should be considered when choosing the optimal treatment for patients.

Closed-loop systems - Update 2020

Closed-loop systems - Update 2020 Abstract. The artificial pancreas (also referred to as a Closed-loop system) represents the latest development in diabetes therapy. Closed-loop systems autonomously direct subcutaneous insulin infusion via a control algorithm based on real-time continuous glucose monitoring. Closed-loop systems have been tested in clinical studies since 2011, and were shown to improve glucose control by reducing hyper- and hypoglycaemia as well as glucose variability when compared with conventional insulin pump therapy. In 2016, the US regulatory authority approved the first hybrid-closed-loop system for the treatment of type 1 diabetes. Hybrid-closed loop systems are not yet fully automated and still require the user to be actively involved for insulin dosing at mealtimes. In spite of the remarkable progress, the delayed action profile of subcutaneously administered insulin and the need to wear multiple devices on the body remain challenging. The present review article summarizes the current state of the art of closed-loop systems in diabetes care and will address technical aspects, evidence from clinical studies as well as future developments in the field.

Sodium-glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus.

The management of type 2 diabetes mellitus (T2DM) is becoming increasingly complex. Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) are the newest antidiabetic agents for T2DM. By targeting the kidney, they have a unique mechanism of action, which results in enhanced glucosuria, osmotic diuresis and natriuresis, thereby improving glucose control with a limited risk of hypoglycaemia and exerting additional positive effects such as weight loss and the lowering of blood pressure. Several outcome studies with canagliflozin, dapagliflozin or empagliflozin reported a statistically significant reduction in major cardiovascular events, hospitalization for heart failure and progression to advanced renal disease in patients with T2DM who have established atherosclerotic cardiovascular disease, several cardiovascular risk factors, albuminuric mild to moderate chronic kidney disease or heart failure. Current guidelines proposed a new paradigm in the management of T2DM, with a preferential place for SGLT2is, after metformin, in patients with atherosclerotic cardiovascular disease, heart failure and progressive kidney disease. Ongoing trials might extend the therapeutic potential of SGLT2is in patients with, but also without, T2DM. This Review provides an update of the current knowledge on SGLT2is, moving from their use as glucose-lowering medications to their new positioning as cardiovascular and renal protective agents.

Linoleic Acid-Rich Oil Supplementation Increases Total and High-Molecular-Weight Adiponectin and Alters Plasma Oxylipins in Postmenopausal Women with Metabolic Syndrome.

ABSTRACTBackgroundThe onset of menopause increases the risk of metabolic syndrome (MetS). Adiponectin is an adipokine associated with insulin sensitivity that is lower in people with MetS. Supplementing diets with linoleic acid (LA)-rich oil increased adiponectin concentrations and improved glucose control in women with type 2 diabetes. The effect of LA on adipokines, especially total and the bioactive form of adiponectin, high-molecular-weight (HMW) adiponectin, in women with MetS is unknown.ObjectivesThe aim of this study was to explore the effect of supplementation of the diet with an oil rich in LA on adipokines in women with MetS. The effect of the LA-rich oil (LA-oil) on oxylipins, key metabolites that may influence inflammation and metabolism, was also explored.MethodsIn this open-label single-arm pilot study, 18 postmenopausal nondiabetic women with MetS enrolled in a 2-phase study were instructed to consume LA-rich vegetable oil (10 mL/d) as part of their habitual diets. Women consumed an oleic acid–rich oil (OA-oil) for 4 wk followed by an LA-oil for 16 wk. Fasting concentrations of adipokines, fatty acids, oxylipins, and markers of glycemia and inflammation were measured.ResultsAfter 4 wk of OA-oil consumption, fasting glucose and total adiponectin concentrations decreased whereas fasting C-reactive protein increased. After 16 wk of LA-oil supplementation total and HMW adiponectin and plasma oxylipins increased. Markers of inflammation and glycemia were unchanged after LA-oil consumption.ConclusionsSupplementation with LA-oil increased total and HMW adiponectin concentrations and altered plasma oxylipin profiles. Larger studies are needed to elucidate the links between these changes and MetS.This trial was registered at clinicaltrials.gov as NCT02063165.

An Artificial Intelligence Characterised Functional Ingredient, Derived from Rice, Inhibits TNF-α and Significantly Improves Physical Strength in an Inflammaging Population.

Food-derived bioactive peptides offer great potential for the treatment and maintenance of various health conditions, including chronic inflammation. Using in vitro testing in human macrophages, a rice derived functional ingredient natural peptide network (NPN) significantly reduced Tumour Necrosis Factor (TNF)-α secretion in response to lipopolysaccharides (LPS). Using artificial intelligence (AI) to characterize rice NPNs lead to the identification of seven potentially active peptides, the presence of which was confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Characterization of this network revealed the constituent peptides displayed anti-inflammatory properties as predicted in vitro. The rice NPN was then tested in an elderly “inflammaging” population with a view to subjectively assess symptoms of digestive discomfort through a questionnaire. While the primary subjective endpoint was not achieved, analysis of objectively measured physiological and physical secondary readouts showed clear significant benefits on the ability to carry out physical challenges such as a chair stand test that correlated with a decrease in blood circulating TNF-α. Importantly, the changes observed were without additional exercise or specific dietary alterations. Further health benefits were reported such as significant improvement in glucose control, a decrease in serum LDL concentration, and an increase in HDL concentration; however, this was compliance dependent. Here we provide in vitro and human efficacy data for a safe immunomodulatory functional ingredient characterized by AI.

Uninterrupted continuous glucose monitoring access is associated with a decrease in HbA1c in youth with type 1 diabetes and public insurance.

Continuous glucose monitor (CGM) use is associated with improved glucose control. We describe the effect of continued and interrupted CGM use on hemoglobin A1c (HbA1c) in youth with public insurance. We reviewed 956 visits from 264 youth with type 1 diabetes (T1D) and public insurance. Demographic data, HbA1c and two-week CGM data were collected. Youth were classified as never user, consistent user, insurance discontinuer, and self-discontinuer. Visits were categorized as never-user visit, visit before CGM start, visit after CGM start, visit with continued CGM use, visit with initial loss of CGM, visit with continued loss of CGM, and visit where CGM is regained after loss. Multivariate regression adjusting for age, sex, race, diabetes duration, initial HbA1c, and body mass index were used to calculate adjusted mean and delta HbA1c. Adjusted mean HbA1c was lowest for the consistent user group (HbA1c 8.6%;[95%CI 7.9,9.3]). Delta HbA1c (calculated from visit before CGM start) was lower for visit after CGM start (-0.39%;[95%CI -0.78,-0.02]) and visit with continued CGM use (-0.29%;[95%CI -0.61,0.02]), whereas it was higher for visit with initial loss of CGM (0.40%;[95%CI -0.06,0.86]), visit with continued loss of CGM (0.46%;[95%CI 0.06,0.85]), and visit where CGM is regained after loss (0.57%;[95%CI 0.06,1.10]). Youth with public insurance using CGM have improved HbA1c, but only when CGM use is uninterrupted. Interruptions in use, primarily due to gaps in insurance coverage of CGM, were associated with increased HbA1c. These data support both initial and ongoing coverage of CGM for youth with T1D and public insurance.

Current status of porcine islet xenotransplantation.

Human islet transplantation has proven to be a highly effective treatment for patients with labile type 1 diabetes mellitus, which can free patients from daily glucose monitoring and insulin injections. However, the shortage of islet donors limits its' broad application. Porcine islet xenotransplantation presents a solution to the donor shortage and recent advances in genetic modification and immunosuppressive regimens provide renewed enthusiasm for the potential of this treatment. Advances in genetic editing technology are leading to multigene modified porcine islet donors with alterations in expression of known xenoantigens, modifications of their complement and coagulation systems, and modifications to gain improved immunological compatibility. Recent NHP-based trials of costimulation blockade using CD154 blockade show promising improvements in islet survival, whereas results targeting CD40 are less consistent. Furthermore, trials using IL-6 receptor antagonism have yet to demonstrate improvement in glucose control and suffer from poor graft revascularization. This review will detail the current status of islet xenotransplantation as a potential treatment for type I diabetes mellitus, focusing on recent advances in porcine xenogeneic islet production, assessment in nonhuman primate preclinical models, the outcome of human clinical trials and review barriers to translation of xenoislets to the clinic.

Systemic AAV10.COMP-Ang1 rescues renal glomeruli and pancreatic islets in type 2 diabetic mice

IntroductionDiabetic hyperglycemia causes progressive and generalized damage to the microvasculature. In renal glomeruli, this results in the loss of podocytes with consequent loss of constitutive angiopoietin-1 (Ang1) signaling, which is...

Exenatide extended release in patients with type 1 diabetes with and without residual insulin production.

To test whether a long-acting GLP-1 receptor agonist would improve glucose control in patients with type 1 diabetes (T1D) and to determine whether the presence of residual beta cell function would affect the response. In addition, we sought to determine whether the drug would affect beta cell function. We performed a randomized placebo-controlled trial of exenatide extended release (ER) in participants with T1D with and without detectable levels of C-peptide. Seventy-nine participants were randomized to exenatide ER 2 mcg weekly, or placebo, stratified by the presence or absence of detectable C-peptide levels. The primary outcome was the difference in glycated haemoglobin (HbA1c) levels at 24 weeks. Participants were followed for another 6 months off study drug. At week 24, the time of the primary outcome, the least squares (LS) mean HbA1c level was 7.76% (95% confidence interval [CI] 7.42, 8.10) in the exenatide ER group versus 8.0% (95% CI 7.64, 8.35) in the placebo group (P = 0.08). At week 12 the LS mean HbA1c levels were 7.71% (95% CI 7.37, 8.05) in the exenatide ER group versus 8.05% (95% CI 7.7, 8.4) in the placebo group (P = 0.01). The improvement at week 12 was driven mainly by those with detectable levels of C-peptide. Those treated with exenatide ER lost weight at 12 and 24 weeks compared to those treated with placebo (P <0.001 and P = 0.007). The total insulin dose was lower, but not when corrected for body weight, and was not affected by residual insulin production. Adverse events were more frequent with exenatide ER, but hypoglycaemia was not increased. Treatment with exenatide ER may have short-term benefits in some individuals with T1D who are overweight or who have detectable levels of C-peptide, but short-term improvements were not sustained.

Nocturnal whey protein ingestion impairs post-prandial glucose tolerance at breakfast.

Poor post-prandial glucose control is a risk factor for multiple health conditions. The second-meal effect refers to the progressively improved glycaemic control with repeated feedings, an effect which is achievable with protein ingestion at the initial eating occasion. The most pronounced glycaemic response each day therefore typically occurs following breakfast, so the present study investigated whether ingesting protein during the night could improve glucose control at the first meal of the day. In a randomised crossover design, fifteen adults (seven males, eight females; age, 22 (sd 3) years; BMI, 24·0 (sd 2·8) kg/m2; fasting blood glucose, 4·9 (sd 0·5) mmol/l) woke at 04.00 (sd 1) hours to ingest 300 ml water with or without 63 g whey protein. Participants then completed a mixed-macronutrient meal tolerance test (1 g carbohydrate/kg body mass, 2356 (sd 435) kJ), 5 h 39 min following the nocturnal feeding. Nocturnal protein ingestion increased the glycaemic response (incremental AUC) to breakfast by 43·5 (sd 55·5) mmol × 120 min/l (P = 0·009, d = 0·94). Consistent with this effect, individual peak blood glucose concentrations were 0·6 (sd 1·0) mmol/l higher following breakfast when protein had been ingested (P = 0·049, d = 0·50). Immediately prior to breakfast, rates of lipid oxidation were 0·02 (sd 0·03) g/min higher (P = 0·045) in the protein condition, followed by an elevated post-prandial energy expenditure (0·38 (sd 0·50) kJ/min, P = 0·018). Post-prandial appetite and energy intake were similar between conditions. The present study reveals a paradoxical second-meal phenomenon whereby nocturnal whey protein feeding impaired subsequent glucose tolerance, whilst increasing post-prandial energy expenditure.

Substitution of parts of aerobic training by resistance training lowers fasting hyperglycemia in individuals with metabolic syndrome.

We sought to determine the effects of substituting parts of aerobic training (AT) by resistance training (RT) on metabolic syndrome (MetS) factors. MetS patients (aged 56 ± 7 years; body mass index 33 ± 5kg·m-2 and 3.9 ± 0.8 MetS factors) were randomized to undergo 1 of the following isocaloric, 16-week long exercise programs: (i) cycling 4 bouts of 4-min at 90% of maximal heart rate (HRmax) followed by 3 sets of 12 repetitions of 3 lower limb free-weight exercises (high-intensity interval training (HIIT)+RT group; n = 33), (ii) cycling 5 bouts of 4 min at 90% of HRmax (HIIT+HIIT group; n = 33), or (iii) no exercise control group (n = 21). We measured the evolution of all 5 MetS components (z score), cardiorespiratory fitness (maximal oxygen uptake), leg strength and power (leg press 1-repetition maximum (1RM) and countermovement jump (CMJ)), fasting blood glucose (FG), fasting insulin, and insulin resistance (homeostasis model assessment 2). Both training groups improved maximal oxygen uptake similarly (170 ± 310 and 190 ± 210 mL O2·min-1; P< 0.001) and z score (-0.12 ± 0.29 and -0.12 ± 0.31 for HIIT+RT and HIIT+HIIT, respectively; P< 0.02). However, only HIIT+RT improved CMJ (P= 0.002) and leg press 1RM above the HIIT+HIIT group (21% vs 6%; P< 0.001). Furthermore, FG only decreased in the HIIT+RT group (5%; P= 0.026, time × group). Our findings suggest that substitution of part of HIIT by leg RT improves glucose control in MetS individuals. Novelty Most studies addressing the efficacy of endurance versus resistance training are not matched by energy expenditure. We found that substituting 20% of AT with RT reduces hyperglycemia in MetS individuals. Training recommendations to regain glycemic control in MetS individuals should include resistance training.

Potential of Moringa oleifera to Improve Glucose Control for the Prevention of Diabetes and Related Metabolic Alterations: A Systematic Review of Animal and Human Studies.

Moringa oleifera (MO) is a multipurpose plant consumed as food and known for its medicinal uses, among others. Leaves, seeds and pods are the main parts used as food or food supplements. Nutritionally rich and with a high polyphenol content in the form of phenolic acids, flavonoids and glucosinolates, MO has been shown to exert numerous in vitro activities and in vivo effects, including hypoglycemic activity. A systematic search was carried out in the PubMed database and reference lists on the effects of MO on glucose metabolism. Thirty-three animal studies and eight human studies were included. Water and organic solvent extracts of leaves and, secondly, seeds, have been extensively assayed in animal models, showing the hypoglycemic effect, both under acute conditions and in long-term administrations and also prevention of other metabolic changes and complications associated to the hyperglycemic status. In humans, clinical trials are scarce, with variable designs and testing mainly dry leaf powder alone or mixed with other foods or MO aqueous preparations. Although the reported results are encouraging, especially those from postprandial studies, more human studies are certainly needed with more stringent inclusion criteria and a sufficient number of diabetic or prediabetic subjects. Moreover, trying to quantify the bioactive substances administered with the experimental material tested would facilitate comparison between studies.

Gravicentric approach to Type 2 Diabetes therapy. &#x0D; The success prediction. A proof-of-concept

This study is the proof-of-concept of our "Gravicentric" theory. This concept is based on several fundamental points: obesity as the main foe; rapid reversibility of the disease; as well as a new perspective on the roles different pharmacological classes play in general, and the role of insulin and GLP-1 analogs, in particular. The paper presents and discusses our experience of the implementation of insulin and GLP-1 analogs. The possibility of "insulin weaning"; the therapeutic approach for over-treated patients; and physiological dosing of insulin is also discussed therein.&#x0D; Objectives&#x0D; Primary: To evaluate the long-term efficacy of GLP-1 analogs in insulin-treated Type 2 Diabetes Mellitus (T2DM) patients.&#x0D; Secondary: To analyze which patient would most likely benefit from this combined treatment.&#x0D; Methods&#x0D; In 54 T2DM patients with a mean disease duration of 17.5 years and a mean extent of insulin therapy of 4.5 years, additional GLP-1 analogs therapy was prescribed. Mean duration of GLP-1 treatment was 25.8 months (2.15 years).&#x0D; During the intervention, clinical, biochemical, and anthropometric parameters were analyzed. Compliance, Hypoglycemia and Metabolic Index (MI) assessments were implemented.&#x0D; Results&#x0D; Mean Glycated hemoglobin (HbA1C) decreased from 9.28 1.43 to 8.54 1.4% on GLP-1 analogs, p 0.01. Total Daily dose of Insulin (TDI) showed considerable reduction: 80.6 42.7 U/day before starting GLP-1 vs.41.0 30.7 U/day on GLP-1, p 0.01. These changes were directly linked to weight loss: BMI has dropped from 35.1 4.8 kg/cm2 before, to 32.8 5.0 kg/cm2 on GLP-1 analogs, with patients losing 6.7 kg on average. Moreover, 13 (24%) participants discontinued at least one kind of insulin, while 7 (13%) stopped taking insulin completely, with simultaneous improvement in diabetes control. No clinically significant hypoglycemia was observed.&#x0D; Post-hoc, the participants were categorized according to each patients ability to reduce TDI by more than 20 U/day, and then split into two groups. Group A 34 patients (64.2%) who successfully reduced TDI; Group B 19 patients (35.8%) who failed to do so. The comparison of the two groups showed the following:&#x0D; &#x0D; Significantly larger virtually twice as large baseline TDI in Group A (97.440.4 U/day vs. 52.231.0 U/day), p 0.001.&#x0D; Very effective BMI reduction (BMI 3.3 2.4 kg/cm2 0.9 1.2 kg/cm2, p 0.001) and much better compliance (1.4 1.1 vs. 2.2 1.0, p 0.02) in Group A.&#x0D; A considerable decline of insulin requirements in group A, on GLP-1 therapy (TDI on GLP-1 was -62.4 31.9 U/day) with no TDI reduction in Group B (TDI on GLP-1 was +0.03 14.1 U/day, p 0.001).&#x0D; &#x0D; Thus, in spite of the fact that on GLP1 therapy HbA1C has declined to the same levels in both groups, patients from group A became much leaner and metabolically healthier.&#x0D; We suggest overtreatment as the critical factor of obesity in Group A.&#x0D; Conclusions&#x0D; Adding GLP-1 analogs to insulin in poorly controlled, insulin-treated T2DM patients resulted in an impressive weight (BMI) reduction with significant improvements in glucose control. This provided for a further decline in insulin resistance and insulin requirements. We suggest that the best candidate for successful GLP-1 analogs therapy is an obese, overtreated and compliant T2DM person. Changes in Metabolic Index (MI) rather than surrogate glycemic parameters (HbA1C) are better predictors of a successful T2DM therapy. Neither the duration of diabetes nor the length of insulin therapy in the past is likely to have a critical role in predicting success. These findings are proof-of-concept of our Gravicentric theory in T2DM.

Six-year Effects Of Power Training On Physical Activity In Older Adults With Type 2 Diabetes

PURPOSE: We examined the effect of power training on long-term changes in physical activity (PA) in older adults with type 2 diabetes (T2D) during a 5-year follow-up of the GREAT2DO randomized control trial. METHODS: 103 participants with T2D and metabolic syndrome (51% male, 67.9 ±5.5 yrs) were randomized to receive power or sham exercise training, 3 times/week for 12 months and followed for another 5 years. During follow-up, the power group was supported to continue, and controls were crossed over to training, but neither group exercised under direct supervision. Total PA was assessed using the Physical Activity Scale for the Elderly and the Homeostasis model assessment: insulin resistance (HOMA2-IR) and glycosylated hemoglobin (HbA1c) were used as indices of IR and glucose homeostasis, respectively. RESULTS: Total PA decreased significantly during the follow-up period (p=0.0001), driven by reductions between 12 and 24 months when full supervision of exercise was withdrawn, followed by relative stability over the next 4 years. Engagement in resistance training (PRT) declined from 76% at 12 months in the original power training group to 43% of those assessed at the 6-year follow-up. Notably, 43% of the original sham group also reported engaging in PRT at 6 years. HbA1c, adjusted for total PA level over the 5 years, and diabetes medication usage were significantly lower at 72 vs. 12 months (p= 0.04), without any effect of original group assignment. However, there was no significant change over the follow-up period for HOMA2-IR, adjusted for PA and medication usage (p= 0.23). CONCLUSION: 5 years after withdrawal of fully supervised power training or sham exercise in initially inactive older adults with T2D, 43% of both groups were engaged in minimally-supervised resistance training in community sites. Although both groups reduced participation in structured exercise after withdrawal of direct supervision at 12 months, stability in Total PA level from 24-72 months along with persistence of PRT in 43% of older adults with diabetes and many progressive co-morbidities is notable and unexpected. We are unaware of any other study of unsupervised PRT in an older clinical cohort in which adherence rates of 43% have been achieved 6 years after initial randomization, accompanied by significant improvements in glucose control.

Resistance Exercise And Cardiometabolic Risk In Prediabetes: A Systematic Review And Meta-analysis

Prediabetes is a highly prevalent precursor to type 2 diabetes, and is also associated with an increased risk of morbidity and mortality. Resistance exercise (RE) is an effective method of reducing cardiometabolic risk factors in persons with a diagnosis of type 2 diabetes, but its efficacy in individuals with prediabetes is unclear. Determining the cardiometabolic impact of RE in prediabetes is necessary for evidence-based exercise prescription for diabetes prevention. PURPOSE: To undertake a systematic review and meta-analysis of randomized and non-randomized control trials examining the effect of RE on cardiometabolic risk factors in individuals with prediabetes. METHODS: PubMed, Cochrane, Web of Science, and Embase databases were searched for published studies of adults at risk for diabetes and who participated in a RE intervention. All studies included randomized or non-randomized control trials. The database search and data extraction were performed by two separate reviewers. A systematic review and meta-analysis were conducted to determine changes in adiposity, glycemic control, insulin resistance, blood lipids/lipoproteins, and blood pressure (BP) following the interventions using a random effects model to assess standardized mean differences (SMD) between RE and control. RESULTS: 10 studies comprising 404 participants were included in the analysis. For RE compared to controls, there were significant improvements in glycosylated hemoglobin (SMD = -0.688; 95% confidence interval [CI] -1.178 to -0.198; p=0.006), fasting plasma glucose (SMD = -0.747; 95% CI -1.003 to -0.460; p<0.001), and total cholesterol (SMD = -0.723; 95% CI -1.177 to -0.27; p=0.002). No changes in waist circumference (SMD = -0.232, 95% CI -.526 to 0.062; p=0.122), insulin resistance (SMD = -0.597, 95% CI -1.65 to 0.457; p=0.267), high-density lipoprotein (SMD = -0.287, 95% CI -0.748 to 0.174; p=0.223) or low-density lipoprotein (SMD = -0.398, 95% CI -1.027 to 0.231; p=0.215) cholesterol, triglycerides (SMD = -0.400, 95% CI -0.850 to 0.050; p=0.081), systolic BP (SMD = -0.16, 95% CI -0.491 to 0.158; p=0.315), or diastolic BP (-0.476, 95% CI -1.05 to 0.105; p=0.108) were found. CONCLUSION: RE appears to be an effective method of improving glucose control, but is less effective in improving blood lipids or blood pressure.

An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients.

Insulin has been used to treat diabetes for almost 100 years; yet, current rapid-acting insulin formulations do not have sufficiently fast pharmacokinetics to maintain tight glycemic control at mealtimes. Dissociation of the insulin hexamer, the primary association state of insulin in rapid-acting formulations, is the rate-limiting step that leads to delayed onset and extended duration of action. A formulation of insulin monomers would more closely mimic endogenous postprandial insulin secretion, but monomeric insulin is unstable in solution using present formulation strategies and rapidly aggregates into amyloid fibrils. Here, we implement high-throughput-controlled radical polymerization techniques to generate a large library of acrylamide carrier/dopant copolymer (AC/DC) excipients designed to reduce insulin aggregation. Our top-performing AC/DC excipient candidate enabled the development of an ultrafast-absorbing insulin lispro (UFAL) formulation, which remains stable under stressed aging conditions for 25 ± 1 hours compared to 5 ± 2 hours for commercial fast-acting insulin lispro formulations (Humalog). In a porcine model of insulin-deficient diabetes, UFAL exhibited peak action at 9 ± 4 min, whereas commercial Humalog exhibited peak action at 25 ± 10 min. These ultrafast kinetics make UFAL a promising candidate for improving glucose control and reducing burden for patients with diabetes.

Comparing The Effects Of Different Modes Of Exercise On Glucose Handling In Young Recreationally Active Men

PURPOSE: The prevalence of type 2 diabetes (T2D) is increasing dramatically and is characterized by insulin resistance (IR). Exercise training is an effective modality to improve IR and acutely can increase post-exercise glucose handling for up to 72 hours. However, there is conflicting evidence as to which mode of exercise elicits the greatest positive effect on glucose handling. The purpose of this study was to compare the effectiveness of different modes of exercise on post-exercise glucose handling in young recreationally active men. METHODS: Twelve (age: 22±3 years) recreationally active men completed 4 separate oral glucose tolerance tests (OGTT) either at rest, or 1.5 hours after moderate-intensity continuous exercise (MICE; 30 min @ 65% VO2peak), low-load high-repetition resistance exercise circuit (LLHR; 20-25 reps/set for 3 sets at 30% 1RM) and high-intensity interval training bout (HIIE; 10x1min at 90% HRmax). Heart rate and blood lactate were taken throughout the exercise bouts. Blood was analyzed for total plasma glucose concentration (mmol/L), c-peptide concentration (ng/mL) and blood insulin concentration (μIU/mL). RESULTS: Average blood glucose concentration during the OGTT was lower following LLHR (6.386 ± 0.261mmol/L, p = 0.03) as compared with MICE (6.839 ± 0.256 mmol/L, p = 0.03) with no differences between baseline (6.625 ± 0.333 mmol/L) and HIIE (6.737 ± 0.267 mmol/L). Glucose area under the curve (AUC) was lower following LLHR (781.76 ± 36.08) as compared to MICE (842.81 ± 35.8; p = 0.033) with no difference compared to baseline glucose AUC (804.61 ± 46.7, p = 0.475). Blood c-peptide concentrations were not significantly different between baseline, MICE, HIIE or LLHR average concentrations. Similar to c-peptide there were no significant differences between blood insulin concentrations post exercise. CONCLUSION: In young, healthy men none of the exercise modes improved glucose handling as compared with baseline. However, LLHR resistance exercise did result in greater glucose clearance than MICE, suggesting that it may be a better modality to improve glucose control. Future work should examine the acute and chronic effects of LLHR resistance exercise on glucose handling in individuals with IR to determine the potential effectiveness of this exercise modality to improve insulin sensitivity.