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Electrophysiological properties of human beta-cell lines EndoC-βH1 and -βH2 conform with human beta-cells.
Hastoy, B, Godazgar, M, Clark, A, Nylander, V, Spiliotis, I, van de Bunt, M, Chibalina, MV, Barrett, A, Burrows, C, Tarasov, AI, et al
Scientific reports. 2018;(1):16994
Abstract
Limited access to human islets has prompted the development of human beta cell models. The human beta cell lines EndoC-βH1 and EndoC-βH2 are increasingly used by the research community. However, little is known of their electrophysiological and secretory properties. Here, we monitored parameters that constitute the glucose-triggering pathway of insulin release. Both cell lines respond to glucose (6 and 20 mM) with 2- to 3-fold stimulation of insulin secretion which correlated with an elevation of [Ca2+]i, membrane depolarisation and increased action potential firing. Similar to human primary beta cells, KATP channel activity is low at 1 mM glucose and is further reduced upon increasing glucose concentration; an effect that was mimicked by the KATP channel blocker tolbutamide. The upstroke of the action potentials reflects the activation of Ca2+ channels with some small contribution of TTX-sensitive Na+ channels. The repolarisation involves activation of voltage-gated Kv2.2 channels and large-conductance Ca2+-activated K+ channels. Exocytosis presented a similar kinetics to human primary beta cells. The ultrastructure of these cells shows insulin vesicles composed of an electron-dense core surrounded by a thin clear halo. We conclude that the EndoC-βH1 and -βH2 cells share many features of primary human β-cells and thus represent a useful experimental model.
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Effects of Concomitant Administration of Sodium Glucose Co-transporter 2 Inhibitor with Insulin on Hemoglobin A1c, Body Mass Index and Serum Lipid Profile in Japanese Type 2 Diabetic Patients.
Kusunoki, M, Natsume, Y, Miyata, T, Tsutsumi, K, Oshida, Y
Drug research. 2018;(12):669-672
Abstract
In patients with type 2 diabetes mellitus who show suboptimal blood glucose control under insulin therapy alone, concomitant treatment with an additional hypoglycemic agent that differs in its mechanism of action from insulin may be considered. We conducted this clinical trial to explore whether further control of increased blood glucose level can be achieved with concomitant use of sodium glucose co-transporter 2 (SGLT2) inhibitor as concomitant with other hypoglycemic therapy, as compared to SGLT2 inhibitor monotherapy, in patients with type 2 diabetes mellitus showing decrease in blood glucose level but less than the effect of insulin monotherapy and there was no significant differences. In the SGLT2 inhibitor monotherapy group, decreases of the serum hemoglobin A1c (HbA1c) level, body weight, body mass index (BMI) and serum triglyceride, and elevation of the serum high density lipoprotein cholesterol concentration were observed as compared to the baseline values. In the type 2 diabetic patients under insulin therapy who received combined insulin plus SGLT2 inhibitor therapy, however decreases in the body weight and BMI, with only a tendency towards decrease of the serum HbA1c value, not reaching statistical significance, were observed. The combined therapy group also showed no appreciable changes of the serum triglyceride level, while the serum adiponectin level increased. The present study data indicate that combined insulin plus SGLT2 inhibitor treatment failed to afford any further improvement of the blood glucose control, as compared to SGLT2 monotherapy, in Japanese type 2 diabetic patients.
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Avocado Fruit on Postprandial Markers of Cardio-Metabolic Risk: A Randomized Controlled Dose Response Trial in Overweight and Obese Men and Women.
Park, E, Edirisinghe, I, Burton-Freeman, B
Nutrients. 2018;(9)
Abstract
Avocados are distinctive fruits having both fats and fibers along with various micronutrients and bioactive phytochemicals. This study aimed to assess the effects of replacing carbohydrate energy in meals with half or whole avocado on postprandial indices of metabolic and vascular health. A single-center, randomized, controlled, 3-arm, 6 h, crossover study was conducted in overweight/obese middle-aged adults (n = 31). Participants consumed energy-matched breakfast meals containing 0 g (Control), 68 g (Half-A) or 136 g (Whole-A) fresh Hass avocado on 3 separate occasions. Post-meal glycemic (p < 0.0001), insulinemic (p < 0.0001) and flow mediated vasodilation (FMD) responses were reduced compared to Control meal (p < 0.01), independent of dose. Nuclear magnetic resonance analyses indicated lower concentrations of triglyceride-rich lipoproteins and higher concentrations of larger high-density lipoprotein (HDL) particles after the Whole-A vs. the Control meal (p = 0.02, p < 0.05, respectively). Race/ethnicity influenced sub-class lipoprotein concentrations (p < 0.05). Oxidized low-density-lipoproteins, monocyte chemoattractant protein-1, and interleukin-6 were not different among meals. Tumor necrosis factor-α tended to be lower after Whole-A vs. Control meal (p = 0.07). Replacing carbohydrate components with avocados in a meal improved FMD, a measure of endothelial function, and improved glycemic and lipoprotein profiles in overweight/obese adults. The study provides insight on the acute cardio-metabolic benefits of incorporating avocados into a meal.
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MANAGEMENT OF DIABETES DURING AIR TRAVEL: A SYSTEMATIC LITERATURE REVIEW OF CURRENT RECOMMENDATIONS AND THEIR SUPPORTING EVIDENCE.
Pavela, J, Suresh, R, Blue, RS, Mathers, CH, Belalcazar, LM
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2018;(2):205-219
Abstract
OBJECTIVE Individuals with diabetes are increasingly seeking pretravel advice, but updated professional recommendations remain scant. We performed a systematic review on diabetes management during air travel to summarize current recommendations, assess supporting evidence, and identify areas of future research. METHODS A systematic review of the English literature on diabetes management during air travel was undertaken utilizing PubMed and MEDLINE. Publications regarding general travel advice; adjustment of insulin and noninsulin therapies; and the use of insulin pumps, glucometers and subcutaneous glucose sensors at altitude were included. Gathered information was used to create an updated summary of glucose-lowering medication adjustment during air travel. RESULTS Sixty-one publications were identified, most providing expert opinion and few offering primary data (47 expert opinion, 2 observational studies, 2 case reports, 10 device studies). General travel advice was uniform, with increasing attention to preflight security. Indications for oral antihyperglycemic therapy adjustments varied. There were few recommendations on contemporary agents and on nonhypoglycemic adverse events. There was little consensus on insulin adjustment protocols, many antedating current insulin formulations. Most publications advocated adjusting insulin pump time settings after arrival; however, there was disagreement on timing and rate adjustments. Glucometers and subcutaneous glucose sensors were reported to be less accurate at altitude, but not to an extent that would preclude their clinical use. CONCLUSION Recommendations for diabetes management during air travel vary significantly and are mostly based on expert opinion. Data from systematic investigation on glucose-lowering medication adjustment protocols may support the development of a future consensus statement. ABBREVIATIONS CSII = continuous subcutaneous insulin infusion (device) DPP-4 = dipeptidyl peptidase 4 EGA = error grid analysis GDH = glucose dehydrogenase GOX = glucose oxidase GLP1 = glucagon-like peptide-1 NPH = neutral protamine Hagedorn SGLT2 = sodium-glucose cotransporter-2.
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Comparison between sodium-glucose cotransporter 2 inhibitors and pioglitazone as additions to insulin therapy in type 2 diabetes patients: A systematic review with an indirect comparison meta-analysis.
Cho, YK, Kim, YJ, Kang, YM, Lee, SE, Park, JY, Lee, WJ, Jung, CH
Journal of diabetes investigation. 2018;(4):882-892
Abstract
AIMS/INTRODUCTION We aimed to evaluate the efficacy and safety of pioglitazone (PIO) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) as additions to insulin therapy for the management of type 2 diabetes mellitus. MATERIALS AND METHODS We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov through December 2016. Randomized controlled trials published in English that compared SGLT2i plus insulin (SGLT2i/INS) or PIO plus insulin (PIO/INS) with placebo plus insulin (PCB/INS) in type 2 diabetes mellitus patients were included. We compared the efficacy and safety between SGLT2i/INS and PIO/INS indirectly. RESULTS A total of 14 randomized controlled trials comparing 7,226 participants were included (8 SGLT2i and 6 PIO studies). SGLT2i/INS achieved similar reductions in hemoglobin A1c (weighted mean difference [WMD] -0.01% [-0.1 mmol/mol], 95% confidence interval [CI] -0.25 to 0.22% [-2.7 to -2.4 mmol/mol]; P = 0.896) and fasting plasma glucose (WMD -0.90 mg/dL, 95% CI: -15.50 to 13.71 mg/dL; P = 0.904), and a similar proportion of participants achieved hemoglobin A1c <7.0% (<53.0 mmol/mol; relative risk 0.98, 95% CI: 0.73 to 1.33; P = 0.917) as compared with the PIO/INS group, with greater weight reduction (WMD -4.54 kg, 95% CI: -5.67 to -3.41 kg; P < 0.001). PIO/INS showed non-significant trends toward a higher risk of hypoglycemia (relative risk 1.15, 95% CI: 0.97 to 1.35; P = 0.102) and higher reduction of total daily insulin doses (WMD -2.45 IU/day, 95% CI: -7.30 to 2.40 IU/day; P = 0.438). CONCLUSIONS Both PIO and SGLT2i are feasible adjunctive oral agents to pre-existing insulin therapy in individuals with inadequately controlled type 2 diabetes mellitus.
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Consumption of a Carbonated Beverage with High-Intensity Sweeteners Has No Effect on Insulin Sensitivity and Secretion in Nondiabetic Adults.
Bonnet, F, Tavenard, A, Esvan, M, Laviolle, B, Viltard, M, Lepicard, EM, Lainé, F
The Journal of nutrition. 2018;(8):1293-1299
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Abstract
BACKGROUND The effects of the regular intake of beverages containing high-intensity sweeteners on insulin sensitivity in healthy individuals remain controversial. OBJECTIVE This trial compared the effects of the consumption of a carbonated beverage containing aspartame and acesulfame K (high-intensity sweeteners beverage-HISB) with those of an unsweetened, no-calorie carbonated beverage (UB) on insulin sensitivity and secretion in nondiabetic adults. METHODS SEDULC was a randomized, double-blind, crossover study. Nondiabetic adults [mean age 31 y, 44% men, body mass index (BMI; kg/m²) 19-29] who did not consume high-intensity sweeteners were randomized 1:1 to drink 1 of the 2 carbonated beverages, 2 cans (330 mL each)/d, for 12 wk. After a 4-wk washout period, participants were switched to the opposite beverage for 12 wk. The primary outcome tested was the change in insulin sensitivity as assessed by the Matsuda Insulin Sensitivity Index (MISI) after an oral glucose load. Secondary outcomes were indexes of insulin secretion. RESULTS Sixty individuals were enrolled and 50 completed the study (28 nonoverweight and 22 overweight participants). The change in MISI from baseline did not significantly differ between beverages and noninferiority was demonstrated (difference = -0.23; 95% CI: -1.31, 0.85; P < 0.0001). The change in insulinogenic (means ± SEMs: 0.23 ± 0.14 for HISB compared with 0.08 ± 0.1 for UB) and disposition indexes (2.70 ± 0.99 for HISB compared with 1.62 ± 0.90 for UB) did not differ, and no differences in insulin secretion estimates were confirmed by the Stumvoll indexes. Consuming the high-intensity sweeteners did not affect body weight, self-reported dietary consumption, or self-reported physical activity. CONCLUSIONS These findings suggest that the daily consumption of 2 cans of a beverage containing aspartame and acesulfame K over 12 wk has no significant effect on insulin sensitivity and secretion in nondiabetic adults. This trial was registered at clinicaltrials.gov as NCT02031497.
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Protocol for Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetes Cases (The MAG1C trial): a randomised, double-blinded, placebo-controlled trial.
Johansen, NJ, Dejgaard, TF, Lund, A, Vilsbøll, T, Andersen, HU, Knop, FK
BMJ open. 2018;(6):e021861
Abstract
INTRODUCTION Persons with type 1 diabetes require intensive insulin therapy to achieve glycaemic control, but side effects, including hypoglycaemia and weight gain, may reduce treatment compliance. We hypothesise that add-on treatment of the short-acting glucagon-like peptide-1 receptor agonist, exenatide, to insulin therapy in persons with type 1 diabetes will reduce insulin requirements, glycaemic excursions and body weight and improve glycaemic control without increasing the risk of hypoglycaemia. The present article describes a protocol developed to test this hypothesis. METHODS AND ANALYSIS One-hundred adult persons with type 1 diabetes for more than 1 year, insufficient glycaemic control (glycated haemoglobin A1c (HbA1c) between 58 and 86 mmol/mol) and body mass index >22.0 kg/m2 will be randomised to either exenatide 10 µg three times per day (at meal times) or placebo as add-on therapy to regular basal-bolus insulin treatment for 26 weeks. Primary endpoint is change in HbA1c between the two groups at end of treatment. Secondary endpoints include change in glycaemic excursions (assessed by continuous glucose monitoring); insulin dose; hypoglycaemic and adverse events; body weight, lean body and fat mass; dietary patterns; quality of life and treatment satisfaction; cardiovascular-disease risk profile; metabolomics; and arginine-tested plasma glucose, glucagon and C-peptide levels. ETHICS AND DISSEMINATION The study is approved by the Danish Medicines Agency, the Regional Scientific Ethics Committee of the Capital Region of Denmark and the Data Protection Agency. The study will be carried out under the surveillance and guidance of the good clinical practice (GCP) unit at Copenhagen University Hospital Bispebjerg in accordance with the ICH-GCP guidelines and the Helsinki Declaration. Positive, negative as well as inconclusive results will be sought disseminated at scientific meetings and in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER NCT03017352.
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Investigation of dose-dependent effects of fat on blood glucose, serum insulin, and appetite sensation.
Yamaguchi, C, Yamanaka-Okumura, H, Esumi, H, Masuda, M, Katayama, T, Taketani, Y
The journal of medical investigation : JMI. 2018;(3.4):203-207
Abstract
Humans have a high preference for fat, and its excessive intake leads to obesity. This study aimed to investigate the effects of dose-dependent fat intake on biological responses and postprandial appetite sensation in healthy adult subjects. Age and body mass index were 29 ± 1 years and 21.1 ± 0.4 kg/m2, respectively. We conducted a randomized, crossover trial and measured laboratory data and appetite sensation via the visual analog scale. Each participant was provided with four different test meals. They consisted of common, basic foods and contained 75 g liquid glucose and 4 slices of crackers to which 0 g butter (control), 10 g butter (B10), 20 g butter (B20), and 40 g butter (B40) were added, respectively. The results indicated that single ingestion of butter did not influence laboratory values of glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), total bile acids, or high-sensitivity CRP (hs-CRP). Regarding postprandial appetite sensation, appetite ratings for fullness were the highest after the B40 meal (p < 0.05);however, satisfaction ratings were not significantly different after the ingestion of this meal. Ratings were significantly different after the B20 meal. In conclusion, healthy adult subjects experienced fullness and satisfaction after ingesting 20-40 g of butter. J. Med. Invest. 65:203-207, August, 2018.
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The glycaemic index and insulinaemic index of commercially available breakfast and snack foods in an Asian population.
Tan, WSK, Tan, WJK, Ponnalagu, SD, Koecher, K, Menon, R, Tan, SY, Henry, CJ
The British journal of nutrition. 2018;(10):1151-1156
Abstract
A low-glycaemic-index (GI) breakfast has been shown to lower blood glucose levels throughout the day. A wide variety of breakfast foods are consumed, but their GI values are largely unknown, hence limiting consumers' ability to select healthier options. This study investigated the GI values of ten common breakfast (five Asian and five Western) foods in this region using a randomised, cross-over study design. Participants arrived after an overnight fast, and fasting blood sample was taken before participants consumed test foods. Next, blood samples were taken at fixed intervals for 180 min. Glycaemic and insulinaemic responses to test foods were calculated as incremental AUC over 120 min, which were subsequently reported as glycaemic and insulinaemic indices. In all, nineteen healthy men (nine Chinese and ten Indians) aged 24·7 (sem 0·4) years with a BMI of 21·7 (sem 0·4) kg/m2 completed the study. Asian breakfast foods were of medium (white bun filled with red bean paste=58 (sem 4); Chinese steamed white bun=58 (sem 3)) to high GI (rice idli=85 (sem 4); rice dosa=76 (sem 5); upma=71 (sem 6)), whereas Western breakfast foods were all of low GI (whole-grain biscuit=54 (sem 5); whole-grain biscuit filled with peanut butter=44 (sem 3); whole-grain oat muesli=55 (sem 4); whole-grain oat protein granola=51 (sem 4); whole-grain protein cereal=49 (sem 3)). The GI of test foods negatively correlated with protein (r s -0·366), fat (r s -0·268) and dietary fibre (r s -0·422) (all P<0·001). GI values from this study contribute to the worldwide GI database, and may assist healthcare professionals in recommending low-GI breakfast to assist in lower daily glycaemia among Asians who are susceptible to type 2 diabetes mellitus.
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Predictors and Clinical Outcomes of Treatment Intensification in Patients With Type 2 Diabetes Uncontrolled on Basal Insulin in a Real-World Setting.
Kallenbach, L, Shui, AM, Cheng, WY, Fan, T, Hu, W, Zichlin, ML, Duh, MS, Ye, F, Levin, PA
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2018;(9):805-814
Abstract
OBJECTIVE To understand factors associated with intensification of basal insulin therapy and treatment impact on clinical outcomes in patients with type 2 diabetes (T2D). METHODS In this retrospective, observational study of the Practice Fusion electronic health record database, eligible patients were adults with T2D, ≥1 basal insulin prescription and office visit in the 6 months before a glycated hemoglobin A1c (A1C) test >7.0% (index date), and no other injectable prescriptions in the 12 months before the index date. Patients were categorized to intensifiers with injectables (rapid-acting insulin [RAI], glucagon-like peptide-1 receptor agonist [GLP-1 RA], or other injectables) or nonintensifiers with injectables (including no change, adding an oral antidiabetes drug, or changing basal insulin dose). Principal outcomes were A1C change, hypoglycemia incidence, and change in body weight. RESULTS Among 14,653 patients, 2,121 (14.5%) and 12,532 (85.5%) were categorized as intensifiers and nonintensifiers with injectables, respectively. Compared with nonintensifiers, intensifiers were more likely to have an endocrinologist as the prescribing physician (odds ratio [OR], 2.52 [95% confidence interval (CI), 2.16 to 2.94]), hypertension (OR, 1.26 [95% CI, 1.08 to 1.47]), higher baseline A1C (OR, 1.22 [95% CI, 1.17 to 1.26]), obesity (OR, 1.17 [95% CI, 1.01 to 1.36]), and higher body mass index (OR, 1.02 [95% CI, 1.01 to 1.03]). In GLP-1 RA intensifiers, the baseline use of dipeptidyl peptidase-4 inhibitors increased the likelihood of intensification. GLP-1 RA intensifiers had equivalent glycemic control to RAI or other injectables, with a nonsignificantly lower risk of hypoglycemia and reduction in body weight. CONCLUSION Addition of GLP-1 RA to basal insulin may be an effective strategy for overcoming clinical inertia with injectable therapy in patients with T2D. ABBREVIATIONS A1C = glycated hemoglobin A1c; BMI = body mass index; CI = confidence interval; DCSI = Diabetes Complications Severity Index; DPP-4 = dipeptidyl peptidase-4; EHR = electronic health record; GLP-1 RA = glucagon-like peptide-1 receptor agonist; ICD-9-CM = International Classification of Diseases-Ninth Revision-Clinical Modification; ICD-10-CM = International Classification of Diseases-Tenth Revision-Clinical Modification; OAD = oral antidiabetes drug; OR = odds ratio; RAI = rapid-acting insulin; SGLT-2 = sodium-glucose cotransporter-2; T2D = type 2 diabetes.