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Intragastric administration of the bitter tastant quinine lowers the glycemic response to a nutrient drink without slowing gastric emptying in healthy men.
Bitarafan, V, Fitzgerald, PCE, Little, TJ, Meyerhof, W, Jones, KL, Wu, T, Horowitz, M, Feinle-Bisset, C
American journal of physiology. Regulatory, integrative and comparative physiology. 2020;(2):R263-R273
Abstract
The rate of gastric emptying and the release of gastrointestinal (GI) hormones are major determinants of postprandial blood-glucose concentrations and energy intake. Preclinical studies suggest that activation of GI bitter-taste receptors potently stimulates GI hormones, including glucagon-like peptide-1 (GLP-1), and thus may reduce postprandial glucose and energy intake. We evaluated the effects of intragastric quinine on the glycemic response to, and the gastric emptying of, a mixed-nutrient drink and the effects on subsequent energy intake in healthy men. The study consisted of 2 parts: part A included 15 lean men, and part B included 12 lean men (aged 26 ± 2 yr). In each part, participants received, on 3 separate occasions, in double-blind, randomized fashion, intragastric quinine (275 or 600 mg) or control, 30 min before a mixed-nutrient drink (part A) or before a buffet meal (part B). In part A, plasma glucose, insulin, glucagon, and GLP-1 concentrations were measured at baseline, after quinine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured. In part B, energy intake at the buffet meal was quantified. Quinine in 600 mg (Q600) and 275 mg (Q275) doses alone stimulated insulin modestly (P < 0.05). After the drink, Q600 and Q275 reduced plasma glucose and stimulated insulin (P < 0.05), Q275 stimulated GLP-1 (P < 0.05), and Q600 tended to stimulate GLP-1 (P = 0.066) and glucagon (P = 0.073) compared with control. Quinine did not affect gastric emptying of the drink or energy intake. In conclusion, in healthy men, intragastric quinine reduces postprandial blood glucose and stimulates insulin and GLP-1 but does not slow gastric emptying or reduce energy intake under our experimental conditions.
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Acute pancreatitis risk in type 2 diabetes patients treated with canagliflozin versus other antihyperglycemic agents: an observational claims database study.
Yuan, Z, DeFalco, F, Wang, L, Hester, L, Weaver, J, Swerdel, JN, Freedman, A, Ryan, P, Schuemie, M, Qiu, R, et al
Current medical research and opinion. 2020;(7):1117-1124
Abstract
Objective: Observational evidence suggests that patients with type 2 diabetes mellitus (T2DM) are at increased risk for acute pancreatitis (AP) versus those without T2DM. A small number of AP events were reported in clinical trials of the sodium glucose co-transporter 2 inhibitor canagliflozin, though no imbalances were observed between treatment groups. This observational study evaluated risk of AP among new users of canagliflozin compared with new users of six classes of other antihyperglycemic agents (AHAs).Methods: Three US claims databases were analyzed based on a prespecified protocol approved by the European Medicines Agency. Propensity score adjustment controlled for imbalances in baseline covariates. Cox regression models estimated the hazard ratio of AP with canagliflozin compared with other AHAs using on-treatment (primary) and intent-to-treat approaches. Sensitivity analyses assessed robustness of findings.Results: Across the three databases, there were between 12,023-80,986 new users of canagliflozin; the unadjusted incidence rates of AP (per 1000 person-years) were between 1.5-2.2 for canagliflozin and 1.1-6.6 for other AHAs. The risk of AP was generally similar for new users of canagliflozin compared with new users of glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sulfonylureas, thiazolidinediones, insulin, and other AHAs, with no consistent between-treatment differences observed across databases. Intent-to-treat and sensitivity analysis findings were qualitatively consistent with on-treatment findings.Conclusions: In this large observational study, incidence rates of AP in patients with T2DM treated with canagliflozin or other AHAs were generally similar, with no evidence suggesting that canagliflozin is associated with increased risk of AP compared with other AHAs.
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The effectiveness of patient activation intervention on type 2 diabetes mellitus glycemic control and self-management behaviors: A systematic review of RCTs.
Almutairi, N, Hosseinzadeh, H, Gopaldasani, V
Primary care diabetes. 2020;(1):12-20
Abstract
BACKGROUND Type 2 diabetes mellitus T2DM is a major health challenge and associated with several complications and mortality. Self-management behaviors SMBs such as healthy diet, physical activity, blood glucose self-monitoring, foot care and medication adherence are critical part of diabetic care. Empowered or activated patients, are more likely to practice better SMBs. However, the effectiveness of patient activation intervention on T2DM glycemic control and SMBs is not totally well understood. AIM: To assess the effectiveness of patient activation intervention on T2DM glycemic control and SMBs. METHOD A systematic search was undertaken through five databases to find relevant studies published between 2004 and 2018. We included randomized controlled trials with sample size ≥120 and follow up period of ≥12 months and assess the effectiveness of patient activation intervention on T2DM glycemic control and SMBs. RESULTS 10 RCTs were identified for analysis. The total sample size is 3728 and the combined mean age is 57.3 years. The combined mean BMI is 31.2kg/m2 (obese). Seven intervention demonstrated a significant reduction in HbA1c, ranged from 0.36 to 0.80%. All interventions presented an improvement in at least one self-management behavior. DISCUSSION AND CONCLUSION Patient activation intervention showed a significant positive effect on T2DM glycemic control and SMBs, particularly physical activity, healthy diet, foot care and blood glucose self-monitoring. The effectiveness on SMBs was seen across different intervention strategies, modes of delivery, length of intervention, and number of providers. Better effectiveness on HbA1c was associated with poorly controlled participants, culturally tailored-intervention, and in-person sessions intervention combined with telephone calls follow up.
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Effects of glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors on major adverse cardiovascular events in type 2 diabetes by race, ethnicity, and region: A meta-analysis.
Qiu, M, Ding, L, Wei, X, Wei, W, Zhou, H
Medicine. 2020;(49):e23489
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Abstract
BACKGROUND The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists on major adverse cardiovascular events (MACE) in type 2 diabetic subgroups defined by race, ethnicity, and region are unestablished. METHODS We searched PubMed and Embase for related randomized controlled trials. We conducted random-effects meta-analysis, stratified by drug class, on MACE in various subgroups defined by 3 factors of interest (ie, race, ethnicity, and region) to estimate pooled hazard ratio (HR) and 95% confidence interval. Random-effects meta-regression was conducted to evaluate the differences between 2 drug classes. RESULTS We included 11 randomized controlled trials for pooled analysis. Compared with placebo, SGLT2is and GLP-1 RAs significantly reduced the risk of MACE (HR ranged from 0.76 to 0.93) in most diabetic subgroups defined by 3 factors of interest. The 2 drug classes did not significantly reduced this risk in the Black race group (HR 0.92, 95% confidence interval 0.70-1.20). The effect of the 2 drug classes on MACE was not significantly different in all diabetic subgroups of interest (P-value for subgroup differences ranged from .101 to .971). CONCLUSIONS SGLT2is and glucagon-like peptide 1 receptor agonists can significantly reduce the risk of MACE in most type 2 diabetic subgroups defined by race, ethnicity, and region, whereas they fail to do it in Black individuals.
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An emerging new concept for the management of type 2 diabetes with a paradigm shift from the glucose-centric to beta cell-centric concept of diabetes - an Asian perspective.
Saisho, Y
Expert opinion on pharmacotherapy. 2020;(13):1565-1578
Abstract
INTRODUCTION Recent advances in anti-diabetic medications and glucose monitoring have led to a paradigm shift in diabetes care. Newer anti-diabetic medications such as DPP-4 inhibitors, GLP-1 receptor agonists (GLP-1RAs), and SGLT2 inhibitors have enabled optimal glycemic control to be achieved without increasing the risk of hypoglycemia and weight gain. Treatment with GLP-1RAs and SGLT2 inhibitors has been demonstrated to improve cardiorenal outcomes, positioning these agents as the mainstay of treatment for patients with type 2 diabetes (T2DM). The development of these newer agents has also prompted a paradigm shift in the concept of T2DM, highlighting the importance of beta cell dysfunction in the pathophysiology of T2DM. AREAS COVERED Recent advances in pharmacotherapy for diabetes are summarized with a focus on the role of incretin-based drugs and SGLT2 inhibitors. The importance of a paradigm shift from a glucose-centric to a beta cell-centric concept of T2DM is also discussed, given from an Asian perspective. EXPERT OPINION Management of T2DM including lifestyle modification as well as pharmacotherapy should be focused on reducing beta cell workload, to preserve functional beta cell mass. A paradigm shift from a glucose-centric to a beta cell-centric concept of T2DM enhances the implementation of person-centered diabetes care.
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Understanding Metabolic Memory: A Tale of Two Studies.
Miller, RG, Orchard, TJ
Diabetes. 2020;(3):291-299
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Abstract
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.
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Dipeptidyl peptidase-4 inhibitor treatment could decrease Klebsiella pneumoniae pneumonia in patients with type 2 diabetes.
Chen, HH, Chen, CC, Ho, CW, Hsieh, MC, Hsu, SP, Lin, CL, Kao, CH
Postgraduate medicine. 2020;(8):714-719
Abstract
OBJECTIVES To investigate the effect of dipeptidyl peptidase-4 inhibitor (DPP4i) for Klebsiella pneumoniae (KP) pneumonia in patients with diabetes. PATIENTS AND METHODS Patients newly diagnosed with type 2 diabetes from 2009 to 2012 were recruited for this population-based and observational study. Diabetes complications severity index (DCSI) score and defined daily dose (DDD) were used for analysis. The multivariable Cox proportional hazards models were used to estimate the risk of KP pneumonia by DPP4i use, with adjustments for propensity score. The Kaplan-Meier method with the log-rank test was used to estimate the risk of KP pneumonia for DPP4i users. RESULTS 34774 patients were included. The incidence rate of KP pneumonia in DDP4i users was 1.51 per 1000 person-years and that for the comparison was 2.25 per 1000 person-years. DDP4i users also had a significantly lower cumulative incidence of KP pneumonia (log-rank test p-value = 0.03). DDP4i users had a significantly lower risk of developing KP pneumonia compared with nonusers (adjusted HR = 0.67, 95% CI = 0.48-0.95). CONCLUSIONS For public health issue with type2 diabetes and infection, DPP4i use decreased KP pneumonia. Male gender, patients with co-morbidities, patients with higher DSCI score and higher DDD of DPP4i were observed to decrease KP pneumonia infection in our analysis. The possible role of DPP4i causing immunological disturbances should be considered.
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Sodium-Glucose Co-Transporter 2 Inhibitors for Non-Alcoholic Fatty Liver Disease in Asian Patients With Type 2 Diabetes: A Meta-Analysis.
Wong, C, Yaow, CYL, Ng, CH, Chin, YH, Low, YF, Lim, AYL, Muthiah, MD, Khoo, CM
Frontiers in endocrinology. 2020;:609135
Abstract
OBJECTIVE Non-alcoholic fatty liver disease (NAFLD) is a very common disorder among patients with type 2 diabetes and may share causal relationship. Type 2 diabetes is a risk factor for progression and potential poor outcomes in NAFLD patients. This meta-analysis aimed to analyze the current evidence of sodium-glucose co-transporter-2 inhibitors (SGLT2i), a glucose-lowering drug to improve NAFLD in patients with Type 2 Diabetes. METHODS Medline, Embase and Cochrane Central Register of Controlled Trials were searched for articles examining efficacy of SGLT2i on treatments of NAFLD in type 2 diabetes in July 2020, and articles were sieved. Continuous data were extracted in the form of mean and standard deviation and were pooled with standardized mean difference (SMD). RESULTS 10 articles involving 555 patients from seven randomized controlled trials (RCTs) and three cohort studies, were included in this meta-analysis. Our analysis revealed significant improvements in hepatic fat content (after treatment: -0.789 (-1.404 to -0.175), p = 0.012; compared with control: -0.923 (-1.562 to -0.285), p = 0.005), AST (After Treatment: -0.539 (-0.720 to -0.357), p < 0.001; compared with control: -0.421 (-0.680 to -0.161), p = 0.001), ALT (after treatment: -0.633 (-0.892 to -0.373), p < 0.001; compared with Control: -0.468 (-0.685 to -0.251), p < 0.001), body composition (BMI: after treatment: -0.225 (-0.456 to 0.005), p = 0.055; compared with Control: -1.092 (-2.032 to -0.153), p = 0.023), glycemic control (HbA1c: After Treatment: -0.701 (-1.098 to -0.303), p = 0.001; compared with control: -0.210 (-0.603 to 0.183), p = 0.295), lipid parameters (Triglycerides: after treatment: -0.230 (-0.409 to -0.052), p = 0.011; compared with control: -0.336 (-0.597 to -0.076), p = 0.011), inflammatory markers (serum ferritin: after treatment: -0.409 (-0.694 to -0.124), p = 0.005; compared with control: -0.814 (-1.688 to 0.059), p = 0.068) after SGLT2i treatment, and when compared against controls. There was a trend in the improvement in fibrosis markers after SGLT2i treatment. CONCLUSIONS SGLT2i is an effective treatment to improve NAFLD among patients with type 2 diabetes. Further studies are needed to understand the direct and indirect effects of SGLT2i on NAFLD and if SGLT2i could prevent the progression of NAFLD or NASH. SGLT2i could potentially be considered for patients with type 2 diabetes and NAFLD, if there are no contraindications.
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Measures of adherence as predictors of early and total weight loss with intensive behavioral therapy for obesity combined with liraglutide 3.0 mg.
Tronieri, JS, Wadden, TA, Walsh, O, Berkowitz, RI, Alamuddin, N, Chao, AM
Behaviour research and therapy. 2020;:103639
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Abstract
Individual weight loss outcomes with intensive behavioral therapy (IBT) for obesity are variable. The present study assessed whether visit attendance, dietary self-monitoring, medication, and meal-replacement adherence were associated with 52-week weight loss with IBT and tested whether these relationships were independent of associations with early weight loss. This was a secondary analysis of a randomized trial in which 150 participants (76.1% female, 55.8% white, BMI = 38.8 ± 4.8 kg/m2) received either IBT alone, IBT with liraglutide 3.0 mg/d, or IBT-liraglutide combined with a 12-week meal replacement diet (Multi-component). In the full sample, visit attendance accounted for 14.8% of the variance in 52-week weight loss and dietary self-monitoring added 14.9%. Only self-monitoring was independently associated with weight loss. In the 100 liraglutide-treated participants, medication adherence accounted for an additional 9.9% of the variance in 52-week weight loss, and both self-monitoring and medication adherence were independent correlates. For the 50 Multi-component participants, meal replacement adherence did not predict weight loss. Early weight loss was associated with higher early and subsequent session attendance and dietary self-monitoring. However, self-monitoring and medication adherence remained important correlates of total weight loss when controlling for this variable. Strategies that help improve self-monitoring consistency and medication usage could improve weight loss with IBT.
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Noninsulin Diabetes Therapies in Older Adults.
Tekin, Z, Zimmerman, RS
Clinics in geriatric medicine. 2020;(3):385-394
Abstract
Diabetes risk increases with age due to changes in β-cell function and increased insulin resistance and is one of the most common chronic medical conditions in the elderly. Diabetes management in this population requires a multidisciplinary, patient-centric approach due to wide heterogeneity in patients' health and functional capacities. Meticulous assessment of each patient before formulating a regimen and thorough patient education are keys to success in achieving glycemic goals, which should be individualized. Lifestyle modification is recommended for every patient.