scholarly journals Vildagliptin Reduces Glucagon during Hyperglycemia and Sustains Glucagon Counterregulation during Hypoglycemia in Type 1 Diabetes

2012 ◽  
Vol 97 (10) ◽  
pp. 3799-3806 ◽  
Author(s):  
Johan Farngren ◽  
Margaretha Persson ◽  
Anja Schweizer ◽  
James E. Foley ◽  
Bo Ahrén
Keyword(s):  
Type 1 Diabetes ◽  
Treatment Period ◽  
Cell Function ◽  
Glycosylated Hemoglobin ◽  
Glucagon Secretion ◽  
Double Blind ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Respective Treatment

Abstract Context: The dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits glucagon secretion at hyperglycemia but appears to enhance glucagon counterregulation during hypoglycemia in type 2 diabetes. Objective: The objective of the investigation was to study whether vildagliptin also improves α-cell function in type 1 diabetes (T1D). Patients and Methods: The study was a single-center, double-blind, randomized, placebo-controlled crossover study involving 28 patients with C-peptide negative and antibody positive T1D [21 males, seven females, glycosylated hemoglobin 57.9 mmol/mol (7.5%)]. Patients received vildagliptin (50 mg twice a day) or placebo as an add-on to their insulin therapy for 4 wk each. On d 28 of the respective treatment period, patients were served a standard meal (500 kcal) to raise the circulating incretin hormone levels followed by a hyperinsulinemic hypoglycemic clamp at 2.5 mmol/liter. Main Outcome Measure: The increase in plasma glucagon levels during the 30-min hypoglycemic clamp (min 165–195 of the test) was measured. Results: During the meal, glucagon levels were lower with vildagliptin than with placebo (120 min area under the curveglucagon 2.4 ± 0.2 vs. 2.6 ± 0.2 nmol/liter × minutes, P = 0.022 for between group difference). In contrast, during hypoglycemia, the glucagon counterregulation was not reduced by vildagliptin (increase in glucagon 1.5 ± 1.0 pmol/liter with vildagliptin vs. 1.7 ± 0.8 pmol/liter with placebo, P = NS). In addition, the counterregulatory responses in epinephrine, norepinephrine, cortisol, and pancreatic polypeptide were not different between the treatments. During the 4-wk treatment period, vildagliptin reduced the mean glycosylated hemoglobin, whereas there was no change with placebo [between group difference was −3.4 ± 1.0 mmol/mol (−0.32 ± 0.09%; P = 0.002)] from baseline of 57.9 mmol/mol (7.5%). Conclusions: Vildagliptin, although inhibiting glucagon secretion during hyperglycemia, does not compromise the glucagon counterregulatory response during hypoglycemia in T1D.

β-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): a randomised, double-blind, phase II trial

The Lancet ◽  
2001 ◽  
Vol 358 (9295) ◽  
pp. 1749-1753 ◽  
Author(s):  
Itamar Raz ◽  
Dana Elias ◽  
Ann Avron ◽  
Merana Tamir ◽  
Muriel Metzger ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Function ◽  
Phase Ii Trial ◽  
Β Cell ◽  
Double Blind ◽  
Β Cell Function ◽  
New Onset

scholarly journals Rate of β-Cell Destruction in Type 1 Diabetes Influences the Development of Diabetic Retinopathy: Protective Effect of Residual β-Cell Function for More Than 10 Years

2008 ◽  
Vol 93 (12) ◽  
pp. 4759-4766 ◽  
Author(s):  
Koji Nakanishi ◽  
Chizuru Watanabe
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Cell Function ◽  
Glycosylated Hemoglobin ◽  
Β Cell ◽  
Historical Cohort ◽  
Cell Destruction ◽  
Β Cell Function ◽  
Onset Of Diabetes

Context: Although residual β-cell function delays the onset and progression of diabetic retinopathy in patients with type 1 diabetes, the rate of β-cell destruction is variable. Objective: The aim of the study was to clarify the influence of the rate of β-cell destruction on the development and progression of diabetic retinopathy in type 1 diabetes. Design: We performed a historical cohort study regarding residual β-cell function and retinopathy. Setting: The study was conducted in the outpatient clinic of a general hospital. Patients: A total of 254 patients with type 1 diabetes participated. Main Outcome Measures: Serum C-peptide and fundus findings were evaluated longitudinally. Results: The cumulative incidence of mild nonproliferative diabetic retinopathy was higher in the patients without detectable β-cell function than in those with residual β-cell function at 20, 15, and 10 yr after the onset of diabetes (P = 0.013, P = 0.006, and P = 0.048, respectively), but not at 5 yr after the onset (P = 0.84). There were higher mean glycosylated hemoglobin values during the entire follow-up period in the patients without detectable β-cell function at 20 and 15 yr after the onset of diabetes (P = 0.030 and P = 0.042, respectively). Positivity for HLA-A24 and -DQA1*03, as well as the acute onset of diabetes, was associated with early β-cell loss and also with early development of diabetic retinopathy. Cox proportional hazards analysis showed that undetectable β-cell function at 20, 15, or 10 yr after the onset of diabetes was an independent risk factor for the development of diabetic retinopathy. Conclusions: Undetectable β-cell function within 10 yr of the onset of type 1 diabetes is associated with the earlier occurrence of diabetic retinopathy.

scholarly journals Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e049595
Author(s):  
John W Gregory ◽  
Kymberley Carter ◽  
Wai Yee Cheung ◽  
Gail Holland ◽  
Jane Bowen-Morris ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Research Ethics ◽  
Beta Cells ◽  
Beta Cell Function ◽  
Cell Function ◽  
Double Blind ◽  
C Peptide ◽  
New Onset

IntroductionMost individuals newly diagnosed with type 1 diabetes (T1D) have 10%–20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis.Methods and analysisThis is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12–18 with new-onset T1D.Participants should have evidence of residual functioning beta-cells (serum C-peptide level >0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible.Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1.MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work.Ethics and disseminationThis trial received research ethics approval from the Wales Research Ethics Committee 3 in September 2018 and began recruiting in December 2018.The results will be disseminated using highly accessed, peer-reviewed medical journals and presented at conferences.Trial registration numberISRCTN14274380.

scholarly journals SGLT2 Inhibition Increases Fasting Glucagon but Does Not Restore the Counterregulatory Hormone Response to Hypoglycemia in Participants with Type 1 Diabetes

2021 ◽  
Author(s):  
Schafer C. Boeder ◽  
Justin M. Gregory ◽  
Erin R. Giovannetti ◽  
Jeremy H. Pettus
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Sglt2 Inhibitor ◽  
Treatment Phase ◽  
Glycemic Variability ◽  
Hormone Response ◽  
Double Blind ◽  
Sodium Glucose Cotransporter ◽  
Sglt2 Inhibition

Individuals with type 1 diabetes have an impaired glucagon counterregulatory response to hypoglycemia. Sodium-glucose cotransporter (SGLT) inhibitors increase glucagon concentrations. We evaluated whether SGLT inhibition restores the glucagon counterregulatory hormone response to hypoglycemia. Adults with type 1 diabetes (<i>n</i> = 22) were treated with the SGLT2 inhibitor dapagliflozin (5 mg daily) or placebo for 4 weeks in a randomized, double-blind, crossover study. After each treatment phase, participants underwent a hyperinsulinemic hypoglycemic clamp. Basal glucagon concentrations were 32% higher following dapagliflozin versus placebo, with a median within-participant difference of 2.75 pg/mL (95% CI 1.38-12.6). However, increased basal glucagon levels did not correlate with decreased rates of hypoglycemia, and thus do not appear to be protective in avoiding hypoglycemia. During hypoglycemic clamp, SGLT2 inhibition did not change counterregulatory hormone concentrations, time to recovery from hypoglycemia, hypoglycemia symptoms, or cognitive function. Thus, despite raising basal glucagon concentrations, SGLT inhibitor treatment did not restore the impaired glucagon response to hypoglycemia. We propose that clinical reduction in hypoglycemia associated with these agents is a result of changes in diabetes care (e.g., lower insulin doses or improved glycemic variability) as opposed to a direct, physiologic effect of these medications on alpha cell function.

scholarly journals Nocturnal antihypertensive treatment in patients with type 1 diabetes with autonomic neuropathy and non-dipping of blood pressure during night time: protocol for a randomised, placebo-controlled, double-blind, two-way crossover study

BMJ Open ◽  
2014 ◽  
Vol 4 (10) ◽  
pp. e006142 ◽  
Author(s):  
Henrik Hjortkær ◽  
Tonny Jensen ◽  
Klaus Kofoed ◽  
Ulrik Mogensen ◽  
Lars Køber ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 1 Diabetes ◽  
Treatment Period ◽  
Left Ventricular Mass ◽  
Left Ventricular ◽  
Night Time ◽  
Double Blind ◽  
Nocturnal Blood Pressure ◽  
Ventricular Mass

IntroductionCardiac autonomic neuropathy (CAN) and elevated nocturnal blood pressure are independent risk factors for cardiovascular disease in patients with diabetes. Previously, associations between CAN, non-dipping of nocturnal blood pressure and coronary artery calcification have been demonstrated. The present protocol describes a trial to test the efficacy of bedtime dosing of the ACE inhibitor enalapril on night time blood pressure and left ventricular mass in patients with type 1 diabetes.Materials and methodsIn a randomised, double-blind, two-way cross-over study, 24 normoalbuminuric patients with type 1 diabetes with CAN will be treated for 12 weeks with either morning or bedtime dosing of 20 mg enalapril, followed by 12 weeks of switched treatment regimen. During each treatment period, two 24 h ambulatory blood pressure measurements will be performed and after each treatment period left ventricular mass will be determined by multisliced CT. Primary end points will be reduction in blood pressure and reduction in left ventricular mass.Ethics and disseminationThe study has been approved by the Danish Medicines Agency, the Scientific-Ethical Committee of the Capital Region of Denmark and the Danish Data Protection Agency. An external monitoring committee (the Good Clinical Practice Unit at Copenhagen University Hospital) will oversee the study. The results of the study will be presented at national and international scientific meetings and publications will be submitted to peer-reviewed journals.Trial registration numberEudraCT (2012- 002136-90).

scholarly journals Effects ofLactobacillus rhamnosusGG andBifidobacterium lactisBb12 on beta-cell function in children with newly diagnosed type 1 diabetes: protocol of a randomised controlled trial

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e017178 ◽  
Author(s):  
Lidia Groele ◽  
Hania Szajewska ◽  
Agnieszka Szypowska
Keyword(s):  
Type 1 Diabetes ◽  
Gut Microbiota ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Controlled Trial ◽  
Lactobacillus Rhamnosus ◽  
Newly Diagnosed ◽  
Double Blind

IntroductionRecent evidence has demonstrated that, among other factors, dysbiosis (imbalances in the composition and function of the gut microbiota) may be relevant in the development of type 1 diabetes (T1D). Thus, gut microbiota may be a target for improving outcomes in subjects with T1D. The aim of the study is to examine the effects ofLactobacillus rhamnosusGG andBifidobacterium lactisBb12 on beta-cell function in children with newly diagnosed T1D.Methods and analysisA total of 96 children aged 8 to 17 years with newly diagnosed T1D, confirmed by clinical history and the presence of at least one positive autoantibody, will be enrolled in a double-blind, randomised, placebo-controlled trial in which they will receiveL. rhamnosusGG andB. lactisBb12 at a dose of 109colony-forming units or an identically appearing placebo, orally, once daily, for 6 months. The follow-up will be for 12 months. The primary outcome measures will be the area under the curve of the C-peptide level during 2-hour responses to a mixed meal.Ethics and disseminationThe Bioethics Committee approved the study protocol. The findings of this trial will be submitted to a peer-reviewed paediatric journal. Abstracts will be submitted to relevant national and international conferences.Trial registration numberNCT03032354; Pre-results.

The dipeptidyl peptidase 4 inhibitor sitagliptin improves oxidative stress and ameliorates glomerular lesions in a rat model of type 1 diabetes

Life Sciences ◽  
2019 ◽  
Vol 234 ◽  
pp. 116738 ◽  
Author(s):  
Catarina Marques ◽  
Andreia Gonçalves ◽  
Patrícia Manuela Ribeiro Pereira ◽  
Daniela Almeida ◽  
Beatriz Martins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 1 Diabetes ◽  
Rat Model ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Glomerular Lesions
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