C-peptide response to glucagon challenge is correlated with improvement of early insulin secretion by liraglutide treatment

Takabe, Michinori; Matsuda, Tomokazu; Hirota, Yushi; Hashimoto, Naoko; Nakamura, Tomoaki; Sakaguchi, Kazuhiko; Ogawa, Wataru; Seino, Susumu

doi:10.1016/j.diabres.2012.09.036

Cited by 23 publications

(16 citation statements)

References 20 publications

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“…Pancreatic β-cell function is reduced by 20% in patients with glucose intolerance and 50% in patients with diabetes [ 15 ]. GLP-1 receptor agonist therapy has been reported to be more effective in patients with relatively high levels of insulin secretion, as determined by the 24-h urinary CPR excretion, the fasting serum CPR level, the CPR index [ 9 ], and the CPR6 [ 10 ]. In this study, however, these markers of insulin secretion were not predictors of the response to GLP-1 receptor agonist therapy.…”

Section: Discussionmentioning

confidence: 99%

Prediction of response to GLP-1 receptor agonist therapy in Japanese patients with type 2 diabetes

Imai

Tsujimoto

Goto

et al. 2014

Diabetol Metab Syndr

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BackgroundGlucagon-like peptide-1 (GLP-1) receptor agonists can maintain good glycemic control in some diabetic. Here we compared the clinical characteristics and parameters reflecting glucose metabolism at the time of the initiation of GLP-1 receptor agonist therapy between patients who responded well to therapy and those who did not.MethodsThe records of 43 patients with type 2 diabetes who started receiving GLP-1 receptor agonist therapy during hospitalization were retrospectively reviewed. Glucagon stimulation tests were performed, and patients were started on liraglutide or exenatide therapy. Preprandial blood glucose levels were measured on days 2 and 3 of GLP-1 receptor agonist therapy. We used the Cox proportional hazard model to compare clinical parameters between responders (HbA1c level <8% at more than 3 months after the initiation of treatment) and non-responders (HbA1c level ≥8% at more than 3 months after the initiation of treatment or a switch to insulin therapy at any time).ResultsTwenty-six of the 43 patients were classified as non-responders. At baseline, mean HbA1c levels were 9.9% among responders and 9.7% among non-responders. Compared with treatment with only diet or metformin, the hazard ratio [HR] for non-response was 5.3 (95% confidence interval [CI]: 1.16-24.6, P = 0.03) for insulin therapy and 5.0 (95% CI: 1.13-22.16, P = 0.03) for sulfonylurea therapy. Compared with the lowest tertile, the HRs for non-response in the highest tertile were 3.1 (95% CI: 1.04-8.97, P = 0.04) for the mean preprandial blood glucose level on days 2 and 3 and 3.4 (95% CI: 1.05-11.01, P = 0.04) for the body mass index. The response was not significantly associated with the duration of diabetes or the glucagon stimulation test results. A receiver operating curve analysis showed that the mean preprandial blood glucose level had the highest area under the curve value (=0.72) for the prediction of non-responders.ConclusionsIn patients with poorly controlled diabetes, the response to GLP-1 receptor agonist therapy was significantly associated with the treatment used before the initiation of therapy, the body mass index, and the mean preprandial blood glucose level during the 2 days after the initiation of therapy.

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Section: Discussionmentioning

confidence: 99%

Prediction of response to GLP-1 receptor agonist therapy in Japanese patients with type 2 diabetes

Imai

Tsujimoto

Goto

et al. 2014

Diabetol Metab Syndr

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“…These results suggest that a large number of patients in the discontinued group exhibited less severe insulin resistance and lower insulin secretion in comparison to the completed group; moreover, patients in the primary ineffective group had less severe insulin resistance and lower insulin secretion than long-term responders. In fact, previous reports have demonstrated significantly improved insulin secretion capacity in response to incretin therapy (25,26).…”

Section: Discussionmentioning

confidence: 99%

A Reduction of HbA1c after 3 Months Predicts 2-year Responsiveness to Sitagliptin Treatment

et al. 2015

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Objective This retrospective study evaluated the long-term efficacy of sitagliptin and the factors contributing to its glucose-lowering effect. Methods Six hundred and sixteen dipeptidyl peptidase-4 inhibitor-naïve outpatients with type 2 diabetes who began sitagliptin treatment between December 1, 2009 and December 31, 2011 were included in this study. The inclusion criteria were that the patient had regularly visited our hospital for a period of ! 700 days from the initiation of sitagliptin treatment and the measurement of hemoglobin A1c (HbA1c) had been performed at 0, 3, 6, 12, 18, and 24 months after the initiation of treatment. From the population of 616 patients, 447 and 169 had received sitagliptin for ! 700 and <700 days, respectively. The primary endpoint was ΔHbA1c at 24 months. The factors associated with the hypoglycemic effect of sitagliptin were also investigated. Results Sitagliptin treatment significantly decreased the level of HbA1c, and the hypoglycemic effect was sustained for at least 2 years. The baseline HbA1c level, duration of diabetes, Δbody weight value, and ΔHbA1c value at 3 months were independently associated with the hypoglycemic effect of sitagliptin. Conclusion Sitagliptin has a long-term hypoglycemic effect in type 2 diabetes patients. A patient's ΔHbA1c at 3 months may be a predictor of their ΔHbA1c at 24 months.

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“…Better insulin response to glucose is seen in those patients taking liraglutide with higher GST c-peptide levels [49]. The clinical relevance of this finding is confirmed by studies showing that fCP and post-meal UCPCR both predict reduction of HbA1c following initiation of treatment with an GLP-1 agonist [50, 51].…”

Section: Prediction Of Response To Non-insulin Therapies In T2dmmentioning

confidence: 97%

A Practical Review of C-Peptide Testing in Diabetes

2017

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C-peptide is a widely used measure of pancreatic beta cell function. It is produced in equimolar amounts to endogenous insulin but is excreted at a more constant rate over a longer time. Methods of estimation include urinary and unstimulated and stimulated serum sampling. Modern assays detect levels of c-peptide which can be used to guide diabetes diagnosis and management. We explore the evidence behind the various tests available. We recommend the glucagon stimulation c-peptide testing owing to its balance of sensitivity and practicality. C-peptide levels are associated with diabetes type and duration of disease. Specifically a c-peptide level of less than 0.2 nmol/l is associated with a diagnosis of type 1 diabetes mellitus (T1DM). C-peptide level may correlate with microvascular and macrovascular complications and future use of insulin therapy, as well as likely response to other individual therapies. We explore the potential uses of c-peptide measurement in clinical practice.

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C-peptide response to glucagon challenge is correlated with improvement of early insulin secretion by liraglutide treatment

Cited by 23 publications

References 20 publications

Prediction of response to GLP-1 receptor agonist therapy in Japanese patients with type 2 diabetes

Prediction of response to GLP-1 receptor agonist therapy in Japanese patients with type 2 diabetes

A Reduction of HbA1c after 3 Months Predicts 2-year Responsiveness to Sitagliptin Treatment

A Practical Review of C-Peptide Testing in Diabetes

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