scholarly journals Reduction in C-Peptide Levels and Influence on Pharmacokinetics and Pharmacodynamics of Insulin Preparations: How to Conduct a High-Quality Euglycemic Clamp Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Tao ◽  
Mingxue Zhu ◽  
Junliang Pu ◽  
Peilin Zhang ◽  
Lei Wan ◽  
...  
Keyword(s):  
Blood Glucose ◽  
C Peptide ◽  
Euglycemic Clamp ◽  
Glucose Levels ◽  
Endogenous Insulin ◽  
Long Acting ◽  
Group B ◽  
Oscillating Glucose ◽  
Clamp Study

Objective: The aim of the study was to investigate the different extent of inhibition of endogenous insulin secretion by the reduction of C-peptide levels in an euglycemic clamp study and its effects on the evaluation of pharmacokinetics, pharmacodynamics of insulin preparations, and quality of clamp study to determine the best reduction range of C-peptide levels.Methods: Healthy Chinese male volunteers were enrolled and underwent a single-dose euglycemic clamp test. Participants were subcutaneously injected with long-acting insulin glargine (0.4 IU/kg). Blood samples were collected pretest and up to 24 h post-test to assess pharmacokinetics (PK), pharmacodynamics (PD), and C-peptide levels.Results: We divided the 39 volunteers enrolled in the study into three groups according to the reduction of C-peptide levels: group A (ratio of C-peptide reduction <30%, n = 13), group B (ratio of C-peptide reduction between ≥ 30% and <50%, n = 15), and group C (ratio of C-peptide reduction ≥50%, n = 11); there were significant differences in the three groups (p= 0.000). The upper and lower limits of blood glucose oscillation in group C was statistically lower than the other groups, the range of oscillating glucose levels in group C was −17.0 ± 6.6% to −1.1 ± 6.7%. The AUC0–24 h in groups A, B, and C were 9.7 ± 2.2, 11.0 ± 2.9, and 11.9 ± 2.1 ng/ml × min, respectively, which indicated an increasing trend in the three groups (Ptrend = 0.041). For quality assessment, the average glucose (p = 0.000) and MEFTG (p = 0.001) levels in three groups were significantly different.Conclusion: The different extent of inhibition of endogenous insulin will influence the PK/PD of insulin preparations and the quality of the euglycemic clamp. Furthermore, the ratio of C-peptide reduction should be above 50% to free from the interference of endogenous insulin, and the range of blood glucose levels should be consistently maintained at −10% to 0 in the euglycemic clamp.

scholarly journals Effects of Unsuppressed Endogenous Insulin On Pharmacokinetics And/Or Pharmacodynamics of Study Insulin In The Healthy: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Hui Liu ◽  
Hongling Yu ◽  
Lisi Sun ◽  
Jingtao Qiao ◽  
Jiaqi Li ◽  
...  
Keyword(s):  
Cohort Study ◽  
Blood Glucose ◽  
Human Insulin ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
C Peptide ◽  
Endogenous Insulin ◽  
Significant Difference ◽  
Group A ◽  
Group B

Abstract Background: C-peptide, a marker of endogenous insulin, should be consistently inhibited during euglycemic clamping, while an elevated postdosing C-peptide (CPpostdosing) is not an occasional phenomenon. This study aimed to describe the effects of insufficient suppression of endogenous insulin on estimates of the pharmacokinetics and pharmacodynamics of subcutaneously injected insulin. Methods: This was a retrospective cohort study that included 33 males who underwent a manual euglycemic clamp with a subcutaneous injection of insulin aspart (IAsp). Time-profiles of whole blood glucose, human insulin, glucose infusion rate (GIR), and C-peptide were recorded. The subjects were divided into two groups at a ratio of 2:1: group A [(CPpostdosing)max＞CPbaseline], group B [(CPpostdosing)max≤CPbaseline]. The endogenous insulin was approximately equal to the measured value of human insulin or calculated from the C-peptide. Results: The basal glucose, CPbaseline, basal human insulin, HOMA-IR, IAsp dose, and demographic statistics were all comparable between the two groups except the ‘clamped’ glucose. The ‘clamped’ glucose was 99.7±7.1% (group A) and 94.9±5.1% (group B) of baseline. After correction for ‘clamped’ glucose, AUCGIR,0-8h was higher in group A (P＜0.05) under comparable IAsp exposure. AUCendogenous insulin,0-8h calculated from C-peptide was different from that measured from human insulin in group A (P＜0.05), whereas no significant difference between these measures was observed in group B. Conclusions: Blood glucose should be controlled below baseline to ensure the inhibition of endogenous insulin. Unsuppressed endogenous insulin may contribute to observed GIR, and the endogenous-insulin-corrected pharmacokinetics estimated by C-peptide may be inaccurate with insufficient endogenous insulin suppression.

The influence of strict control on diabetic complications

1985 ◽  
Vol 110 (4_Suppl) ◽  
pp. S57-S60 ◽  
Author(s):  
Kristian F. Hanssen ◽  
Knut Dahl-Jørgensen ◽  
Olaf Brinchmann-Hansen ◽  
_ _
Keyword(s):  
Blood Glucose ◽  
Diabetic Complications ◽  
Blood Glucose Control ◽  
Response Duration ◽  
Proliferative Retinopathy ◽  
C Peptide ◽  
Acting Insulin ◽  
Strict Control ◽  
Long Acting ◽  
Retinal Response

Abstract. We studied 45 IDDM without c-peptide response, duration 7-22 years, without proliferative retinopathy. After 2 months run-in period, they were randomly assigned to: (P) 15 received CSII: (C) 15 received muliple s.c. injections via butterfly 5-6x daily;: (M) 15 received twice daily mixed rapid and long acting insulin. All groups improved blood glucose control in the run-in period (p<0.0001). After change of treatment (P) and (M) improved further (p<0.01) but (C) was unchanged. GFR was supranormal and decreased in (P) and (M). No regression of retinopathy was shown in any group. One in (P) had transient florid pre-proliferative retinopathy which regressed spontaneously without laser treatment. We conclude that retinal response to strict control is complex. A transient deterioration may been seen.

scholarly journals Dose-Dependent Effects of Recombinant Human Interleukin-6 on Glucose Regulation

1997 ◽  
Vol 82 (12) ◽  
pp. 4167-4170 ◽  
Author(s):  
Constantine Tsigos ◽  
Dimitris A. Papanicolaou ◽  
Ioannis Kyrou ◽  
Ruby Defensor ◽  
Constantine S. Mitsiadis ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Interleukin 6 ◽  
Peak Plasma ◽  
Fasting Blood Glucose ◽  
Peripheral Resistance ◽  
C Peptide ◽  
Inflammatory Stress ◽  
Glucose Levels ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Inflammatory cytokines have metabolic actions that probably contribute to the general adaptation of the organism during infectious or inflammatory stress. To examine the effects of interleukin 6 (IL-6), the main circulating cytokine, on glucose metabolism in man, we performed dose-response studies of recombinant human IL-6 in normal volunteers. Increasing single doses of IL-6 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/Kg BW) were injected sc in 15 healthy male volunteers (3 in each dose) after a 12-h fast. All IL-6 doses were tolerated well and produced no significant adverse effects. We measured the circulating levels of glucose, insulin, C-peptide, and glucagon at baseline and half-hourly over 4 h after the IL-6 injection. Mean peak plasma levels of IL-6 were achieved between 120 and 240 min and were 8, 22, 65, 290, and 4050 pg/mL, respectively, for the 5 doses. After administration of the 2 smaller IL-6 doses, we observed no significant changes in plasma glucose levels, which, because of continued fasting, decreased slightly over time. By 60 min after the 3 higher IL-6 doses, however, the decline in fasting blood glucose was arrested, and glucose levels increased in a dose-dependent fashion. The concurrent levels of plasma insulin and C-peptide were not affected by any IL-6 dose. In contrast, IL-6 caused significant increases in plasma glucagon levels, which peaked between 120 and 150 min after the IL-6 injection. In conclusion, sc IL-6 administration induced dose-dependent increases in fasting blood glucose, probably by stimulating glucagon release and other counteregulatory hormones and/or by inducing peripheral resistance to insulin action.

A Review of Type 1 Diabetes (T1D)

2020 ◽  
pp. 13-49
Author(s):  
Eileen O'Donnell ◽  
Liam O'Donnell
Keyword(s):  
Type 1 Diabetes ◽  
Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Acting Insulin ◽  
Short Period ◽  
Sporting Activities ◽  
To Come

The diagnosis of Type 1 Diabetes (T1D) will come as an unwelcome surprise to most people. Within a short period of time, the person will have to come to understand and manage this chronic illness. The terminology associated with the T1D condition will also be totally new to the person: diabetes mellitus, pancreas, hyperglycaemia (hyper), hypoglycaemia (hypo), bolus (fast acting insulin), basal (slow acting insulin), ketones and blood glucose levels. The purpose of this article is to assist newly diagnosed patients' understanding of T1D, people who are already living with T1D, carers of people with T1D, partners and family members of someone with T1D, work colleagues, and friends who participate in the same sporting activities or go on holiday with a person who has T1D. In addition, this article reviews how people living with T1D can still enjoy exercise and maintain the best quality of life possible; whilst controlling the blood glucose levels in their body for the rest of their lives to prevent the onset of complications associated with diabetes.

scholarly journals Effects of Controling of Post Operative Hypergycemia (Stress Induced Hyperglycemia) in Adult Non-Diabetic Patients Undergoing Mitral Valve Replacement Surgery Under Cardiopulmonary Bypass

2019 ◽  
Vol 34 (1) ◽  
pp. 44-51
Author(s):  
Md Armane Wadud ◽  
Syed Tanvir Ahmed ◽  
Shahnoor Aziz ◽  
Ibrahim Khalilullah ◽  
CM Shaheen Kabir
Keyword(s):  
Blood Glucose ◽  
Mitral Valve ◽  
Valve Replacement ◽  
Mitral Valve Replacement ◽  
Postoperative Morbidity ◽  
Replacement Surgery ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Group B ◽  
Valve Replacement Surgery

Objectives: The objective of this study was to see whether there is an association between high blood glucose levels after operation under CPB and post operative morbidity and mortality. Methodology: This cohort study was carried out in the Department of Cardiac Surgery at National Institute of Cardiovascular DiseaseS (NICVD), Sher-e-Bangla Nagar, Dhaka from January, 2012 to December, 2013 for a period of twenty four (24) months. A total number of 110 patients who underwent MVR operation with CPB were enrolled in this study as per inclusion and exclusion criteria. Patients were divided into two groups according to their post operative blood glucose levels, recorded with in first 60 hrs after mitral valve replacement surgery under cardiopulmonay bypass. Patients having blood glucose level of less than 10.1 mmol/L (unexposed) and patients having blood lactate level of 10.1 mmol/L or more (exposed) were grouped. Post operative variables were observed and recorded during the hospital course of the patient. Result: A total number of 110 patients were enrolled in this study. Blood glucose levels lower than or equal to10 mmol/L after MVR were present in 55(50%) patients (Group A) Blood glucose levels higher than 10 mmol/L after MVR were present in 55(50%) patients. Postoperative morbidity was higher in this group ( Group B) than in the patients who had peak blood glucose levels of less than or equal to 10 mmol/L MVR (p 0.001). Postoperative ICU stay was prolonged in patients with elevated levels of blood glucose after MVR under CPB compared with of patients with lower blood glucose levels (p 0.001). Other common morbidities are neurological complication (p 0.04), renal dysfunction (p 0.01) , wound infection (p 0.04), post-operative hospital stay ( p0.004). also higher in group B patient, as well as mortality. Conclusions: Blood glucose concentration of 10.1 mmol/ L or higher after MVR under CPB is an important issues related to postoperative morbidity and mortality. Bangladesh Heart Journal 2019; 34(1) : 44-51

scholarly journals An evaluation of randomized controlled trials on nutraceuticals containing traditional Chinese medicines for diabetes management: a systematic review

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Junnan Shi ◽  
Hao Hu ◽  
Joanna Harnett ◽  
Xiaoting Zheng ◽  
Zuanji Liang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Randomized Controlled Trials ◽  
Diabetes Management ◽  
Fasting Blood Glucose ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Glucose Levels ◽  
Randomized Controlled ◽  
Blood Glucose Levels

Abstract Background Nutraceuticals containing traditional Chinese medicine (TCM) are promoted for use in the management of diabetes. The evidence to support such use is largely unknown. This study aimed to summarise and evaluate the literature reporting the results of randomized controlled trials (RCTs) investigating the effects of nutraceuticals in people living with diabetes. Methods Literature from four electronic databases (PubMed, Scopus, CINAHL and Web of Science) was searched following PRISMA guidelines to yield RCT publications on nutraceutical for diabetes management published since 2009. The quality of reporting was assessed using the CONSORT 2010 checklist statement. Risk-of-bias for each study was assessed using the Cochrane risk of bias tool. Results Out of 1978 records identified in the initial search, 24 randomized, double/triple-blinded, controlled trials that investigated the effect of nutraceuticals covering 17 different TCM herbs for diabetes management were selected. Participants included people who were diabetic (n = 16), pre-diabetic (n = 3) or predisposed to diabetes (n = 5). Sample sizes ranged between 23 and 117 for 2 arms, or 99–165 for 3 arms. Comparisons were made against placebo (n = 22), conventional medicine (n = 1), or regular diet (n = 1) for a duration between 4 and 24 weeks. All but one study tested the effect on fasting blood glucose levels (n = 23) or glycated haemoglobin levels (n = 18), and/or postprandial 2-h blood glucose levels (n = 4) as the primary outcomes. Nineteen studies reported some statistically significant reductions in the respective measures while 5 studies showed no effect on primary or secondary outcomes. None of the included studies met all the criteria for the CONSORT guidelines. Incomplete reporting about randomization and blinding, and a lack of ancillary analyses to explore other influential factors and potential harms associated with the use were repeatedly noted. Based on the Cochrane risk-of-bias tool, 19 studies were deemed to have a high risk of bias mainly attributed to sponsor bias. Conclusions There is some evidence to suggest positive clinical outcomes in response to the administration of a range of nutraceuticals containing TCM in the management of diabetes. However, these results must be interpreted with caution due to the overall low quality of the trials.

Effectiveness of acarbose in treating elderly patients with diabetes with postprandial hypotension

2017 ◽  
Vol 65 (4) ◽  
pp. 772-783 ◽  
Author(s):  
Jie Zhang ◽  
Lixin Guo
Keyword(s):  
Blood Pressure ◽  
Blood Glucose ◽  
Elderly Patients ◽  
Controlled Trial ◽  
Clinical Trial Registry ◽  
Postprandial Hypotension ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Patients With Diabetes ◽  
Group B

Postprandial hypotension (PPH) is a common condition that occurs primarily in elderly patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the effectiveness of acarbose for PPH; it also investigated possible mechanisms behind PPH development. This single-blind, randomized controlled trial included 91 elderly patients with T2DM, aged between 60 and 80 years, who were inpatients at Beijing Hospital between March 2012 and November 2014. The patients were included into one of three groups: Group A, patients with T2DM without PPH; Group B, patients with T2DM with PPH receiving placebo; and Group C, patients with T2DM with PPH receiving acarbose. After an overnight fast, patients received a single dose of acarbose (100 mg) or placebo and then consumed a standardized 450 kcal meal. Blood pressure, glucose levels, heart rate (HR), and catecholamine levels were evaluated. Acarbose ameliorated PPH as determined by significant improvements in the duration and maximal fall in blood pressure (both p<0.001); however, no differences in HR and blood glucose levels were observed. In patients with PPH, blood pressure was correlated with blood glucose and HR variability values (p<0.05). Correlations between epinephrine and glucagon-like peptide-1 with blood pressure in groups A and C were largely lost in group B. Acarbose reduced postprandial blood pressure fluctuations in elderly patients with diabetes. PPH may be related to impaired autonomic nervous system function, reduced catecholamine secretion, and postprandial fluctuations in blood glucose levels.Trial registration numberChinese Clinical Trial Registry ChiCTR-IPR-15006177.

Effects of exogenous growth hormone pretreatment on the pituitary growth hormone response to growth hormone-releasing hormone alone or in combination with pyridostigmine in Type I diabetic patients

1991 ◽  
Vol 125 (5) ◽  
pp. 510-517 ◽  
Author(s):  
Andrea Giustina ◽  
Simonetta Bossoni ◽  
Corrado Bodini ◽  
Antonino Cimino ◽  
Giuseppe Pizzocolo ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Blood Glucose ◽  
Normal Subjects ◽  
Diabetic Patients ◽  
Type I ◽  
Gh Secretion ◽  
Glucose Levels ◽  
Group A ◽  
Group B ◽  
And Control

Abstract. We evaluated the effects of iv pretreatment with exogenous GH on the GH response to GHRH either alone or in combination with pyridostigmine in 14 Type I diabetic patients and 6 normal subjects. All the subjects received an iv bolus injection of biosynthetic human GH, 2 IU; 2 h later they received either a. pyridostigmine, 120 mg orally, or b. placebo, 2 tablets orally, followed 1 h later by iv injection of GHRH(1-29) NH2, 100 μg. In normal subjects the median GH peak after GH+GHRH was 1.8, range 1.2-6.9 μg/l. Pyridostigmine enhanced the GH response to GHRH in all subjects. The median GH peak after pyridostigmine+ GH+GHRH was 32.7, range 19.8-42.1 μg/l (p<0.001 vs GHRH alone). Seven diabetic subjects had median GH peaks after GH+GHRH >6.9 μg/l (the maximum GH peak after GH+GHRH in normal subjects) (group A: median GH peak 35.7, range 21.7-55 μg/l). The other diabetic subjects had GH peak lower than 6.9 μg/l (group B: median GH peak 4.4, range 2.1-6.5 μg/l). Pyridostigmine significantly increased the GH response to GHRH in group B patients (median GH peak 29.3, range 15.7-93.4 μg/l, p<0.001 vs GH+GHRH alone), but not in group A patients (median GH peak 39.9, range 21.9-64.9 μg/l). Group A diabetic patients were younger and had higher HbA1c and blood glucose levels than group B patients. In those diabetic patients with an exaggerated GH response to GH+GHRH, pyridostigmine failed to cause the increase in GH secretion observed in diabetic and control subjects with no responses to GH+GHRH. It can be suggested that elevated 24-h GH levels in some Type I diabetic patients may be due to decreased somatostatinergic tone which in turn causes altered autoregulation of GH secretion. We hypothesize that this finding is a consequence of a reset of the hypothalamic control of GH secretion caused by a chronically elevated blood glucose level in this subpopulation.

scholarly journals Preventive Effect of Salicylate and Pyridoxamine on Diabetic Nephropathy

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Tarek Kamal Abouzed ◽  
Seiichi Munesue ◽  
Ai Harashima ◽  
Yusuke Masuo ◽  
Yukio Kato ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Macrophage Infiltration ◽  
Gene Expressions ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Developmental Factors ◽  
Blood Glucose Levels ◽  
Patients With Diabetes ◽  
Long Acting

Objective. Diabetic nephropathy is a life-threatening complication in patients with long-standing diabetes. Hemodynamic, inflammatory, and metabolic factors are considered as developmental factors for diabetic nephropathy. In this study, we evaluated whether pharmacological interventions with salicylate, compared to pyridoxamine, could prevent diabetic nephropathy in mice. Methods. Male mice overexpressing inducible nitric oxide synthase in pancreatic β-cells were employed as a diabetic model. Salicylate (3 g/kg diet) or pyridoxamine (1 g/L drinking water; ~200 mg/kg/day) was given for 16 weeks to assess the development of diabetic nephropathy. Treatment with long-acting insulin (Levemir 2 units/kg twice a day) was used as a control. Results. Although higher blood glucose levels were not significantly affected by pyridoxamine, early to late stage indices of nephropathy were attenuated, including kidney enlargement, albuminuria, and increased serum creatinine, glomerulosclerosis, and inflammatory and profibrotic gene expressions. Salicylate showed beneficial effects on diabetic nephropathy similar to those of pyridoxamine, which include lowering blood glucose levels and inhibiting macrophage infiltration into the kidneys. Attenuation of macrophage infiltration into the kidneys and upregulation of antiglycating enzyme glyoxalase 1 gene expression were found only in the salicylate treatment group. Conclusions. Treatment with salicylate and pyridoxamine could prevent the development of diabetic nephropathy in mice and, therefore, would be a potentially useful therapeutic strategy against kidney problems in patients with diabetes.

scholarly journals Analysis of the quality of life of patients with type 1 diabetes mellitus in real clinical practice who received insulin degludec

2021 ◽  
pp. 96-103
Author(s):  
L. A. Suplotova ◽  
A. S. Sudnitsyna ◽  
N. V. Romanova
Keyword(s):  
Quality Of Life ◽  
Type 1 Diabetes ◽  
Diabetes Type ◽  
Insulin Degludec ◽  
Diabetes Type 1 ◽  
Glucose Levels ◽  
Patients With Diabetes ◽  
Long Acting

Introduction. Long-term and high-quality glycemic control prevents the development of vascular complications of diabetes type 1 and improves the disease prognosis, significantly increasing life expectancy. A decrease in the quality of life (QOL) of patients with diabetes type 1 is associated with the disease complications development and carbohydrate metabolism status. In connection with the proven advantages of using indicators of time spent in glycemic ranges (TIR, TAR, TBR), the study of their associations with QOL in patients with type 1 diabetes when switching from long-acting analog insulins to insulin degludec is of particular interest.Aims. To assess the quality of life with diabetes type 1 when switching from long-acting analogs to insulin degludec in real world clinical practice.Materials and methods. The study was designed as a prospective, single-center, uncontrolled study. The recruitment of patients with diabetes type 1 who did not achieve the target values of control of carbohydrate metabolism control, who were on therapy with long-acting and ultrashort-acting analog insulin therapy, was carried out in accordance with the matching criteria. The calculation of TIR and TBR was carried out employing the data from professional continuous monitoring of glucose levels and selfmonitoring of blood glucose levels. The SF-36 Health Status Survey was used to assess QoL.Results. The study included 26 patients who met the inclusion criteria and did not have the exclusion criteria. The relationships between TIR, TBR and QoL parameters during insulin degludec therapy were revealed - with vitality, bodily pain, mental health, which demonstrates an increase in QoL mainly due to the mental component of health.Conclusions. Switching patients with type 1 diabetes from long-acting analog insulins to ultra-long-acting analog insulin on an outpatient basis provides an improvement in glycemic control due to HbA1c and TIR, TBR, and also increases QOL satisfaction, mainly due to the mental component of health.

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