C-peptide Immunoreactivity Index Research Articles

Younger patients and low c-peptide immunoreactivity index but not nutritional states affect fasting blood ketone levels in Japanese with type 1 diabetes after sodium-glucose cotransporter 2 inhibitor administration.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are available for individuals with type 1 diabetes, but appropriate use is recommended to prevent ketosis or ketoacidosis. This study aimed to evaluate the risk of ketosis in people with type 1 diabetes, focusing on the relationship between nutritional assessment, glycaemic status, c-peptide immunoreactivity (CPR) index and body composition. In total, 46 Japanese patients with type 1 diabetes were included, and dietary assessment from food photographs and ketone levels were evaluated before and after taking SGLT2is. The effect of diet on morning ketone levels was also investigated. All patients had an increase in mean ketone concentrations after taking SGLT2is (before 0.12 ± 0.06 mmol/L, after 0.23 ± 0.16 mmol/L). A significant negative correlation was found between average morning ketone levels and age (r = -0.514, p < .001) and the CPR index (r = -0.523, p = .038) after taking SGLT2is. Using a mixed-effects model based on the results before starting the inhibitors, it was noted that both patient-to-patient and age, or patient-to-patient and capacity of insulin secretion, influenced the ketone levels. Multiple regression analysis showed that factors associated with the risk of increasing ketone levels after taking SGLT2is were younger age (β = -0.504, p = .003) and a low ratio of basal to bolus insulin (β = -0.420, p = .005). When administering SGLT2is to patients with a low CPR index or younger patients with type 1 diabetes, adequate instructions to prevent ketosis should be given.

Casual C peptide index: Predicting the subsequent need for insulin therapy in outpatients with type 2 diabetes under primary care.

BackgroundEvaluation of residual beta cell function is indispensable in patients with type 2 diabetes as it informs not only diagnoses but also appropriate treatment modalities. However, there is a lack of convenient biomarkers for residual beta cell function. Therefore, we evaluated endogenous insulin level as a biomarker in outpatients who were being treated with insulin therapy and in patients who were introduced to insulin therapy after 4 years.MethodsData of 174 outpatients with type 2 diabetes (50% male) whose glycemia was moderately controlled (glycated A1c 7.3% [5.2%–14.8%]) were reviewed. Twenty patients whose estimated glomerular filtration rate was lower than 30 ml/min/1.73 m2 were excluded from the evaluation of endogenous insulin level with both casual C‐peptide index (C‐CPI) and urinary C‐peptide/creatinine ratio (determined at any time, generally 1–2 h after breakfast). Patients were stratified based on the provision of insulin therapy.ResultsC‐CPI and UCPCR were significantly lower in the insulin‐treated patients than in the insulin‐untreated patients (0.9 vs. 2.2, p < 0.0001; 24.7 vs. 75.5, p = 0.0003, respectively). Moreover, C‐CPI were significantly lower in the insulin‐requiring patients for 4 years than in the insulin‐unrequiring patients (1.0 vs. 1.7, p = 0.0184). The multivariate logistic regression analysis revealed that both indicators of insulin secretion influenced the requirement for insulin therapy, but C‐CPI could serve as the most convenient and useful biomarker for not only current insulin therapy requirements (p = 0.0002) but also the subsequent requirement for insulin therapy (p = 0.0008).ConclusionsC‐CPI could be determined easily, and it was found to be a more practical marker for outpatients; therefore, our findings would have critical implications for primary care.

Pancreatic fat accumulation evaluated by multidetector computed tomography in patients with type2 diabetes.

AimsTo clarify the clinical impact of pancreatic fat volume on beta cell function in type 2 diabetes patients.Materials and MethodsOne hundred thirty two consecutive type 2 diabetic patients (mean age, 63.7 years) were enrolled in this cross‐sectional study. Total pancreatic volume (TPV), pancreatic fat volume (PFV), and pancreatic parenchymal volume (PPV), and visceral fat volume were examined quantitatively with multidetector computed tomography using SYNAPSE VINCENT image analysis system (Fujifilm Inc., Tokyo, Japan). Pancreatic fat was identified using Hounsfield Units of less than zero. The capacity of insulin secretion was assessed by C‐peptide immunoreactivity (CPR) index (100 × fasting CPR/fasting plasma glucose). Insulin sensitivity was evaluated using CPR‐insulin resistance (20/fasting CPR × fasting plasma glucose).ResultsTPV, PFV, PPV, and visceral fat volume were significantly correlated with body weight (BW). PPV/BW, but not PFV/BW, significantly decreased with increasing duration of diabetes and aging. PFV/BW was positively associated with body mass index and visceral fat volume/BW. PFV/BW was significantly correlated with CPR index, while inversely associated with insulin sensitivity. CPR index, but not CPRinsulin resistance was progressively decreased in patients with a longer duration of diabetes. When patients were divided into two groups according to a median PFV/BW value, CPR index in high PFV/BW group with diabetes duration >5 years was significantly lower than those ≤5 years. However, duration‐dependent decrease in CPR index was not observed in low PFV/BW group.ConclusionsOur present study suggests that PFV might predict the progression of beta cell dysfunction in patients with type 2 diabetes.

Sitagliptin versus mitiglinide switched from mealtime dosing of a rapid-acting insulin analog in patients with type 2 diabetes: a randomized, parallel-group study

PurposeWe determined the feasibility of substituting sitagliptin or mitiglinide for bolus insulin injection therapy in patients with type 2 diabetes.Methods60 patients with type 2 diabetes were enrolled and randomized to...

C-peptide immunoreactivity index is associated with improvement of HbA1c: 2-Year follow-up of sitagliptin use in patients with type 2 diabetes

AimsThis retrospective study aimed to determine the hypoglycaemic effect of 2 years of sitagliptin administration in terms of changes in HbA1c and C-peptide immunoreactivity (CPR) index (plasma CPR [ng/mL]/glucose [mg/dL]×100). MethodsThe inclusion criteria for DPP-4 inhibitor-naive outpatients with type 2 diabetes (n=285) were: continuation of sitagliptin for ≥700 days from initial administration and measurement of HbA1c, serum CPR, and plasma glucose levels at 0, 3, 6, 12, 18, and 24 months after sitagliptin initiation. Logistic regression analyses determined the factors contributing to the response to sitagliptin, based on responder (ΔHbA1c ≤−0.4% [≤−4mmol/mol]) and non-responder (ΔHbA1c >−0.4% [>−4mmol/mol]) groups. ResultsThe HbA1c level decreased and CPR index increased from baseline to 3, 6, 12, 18, and 24 months after the start of sitagliptin administration (HbA1c: 7.4±0.8% [57±9mmol/mol], 7.3±0.9% [57±9mmol/mol], 7.4±0.9% [58±10mmol/mol], 7.1±0.8% [55±9mmol/mol], and 7.3±0.9% [57±10mmol/mol], respectively, all P<0.001 vs. baseline [8.0±1.0%, 64±11mmol/mol] and CPR index: 1.69±0.96, 1.71±1.10, 1.62±0.96, 1.64±0.92, and 1.66±0.96, respectively, all P<0.05 vs. baseline [1.47±0.81]). Higher baseline HbA1c level, shorter diabetes duration, and greater CPR index increase after sitagliptin administration were associated with the response to sitagliptin. ConclusionsOur results suggest that sitagliptin improves glycaemic control via an improved intrinsic insulin response.

Serum C-peptide to plasma glucose ratio may be associated with efficacy of vildagliptin in Japanese patients with type 2 diabetes mellitus

This retrospective study was undertaken to clarify the characteristics of patients in whom vildagliptin exerts its HbA1c-lowering effect fully. The safety of vildagliptin was also examined. Vildagliptin was administered as initial, additive, or exchange medication to 139 type 2 diabetic patients. Patients were excluded if they had a change in another oral hypoglycemic agent within 24 weeks after starting vildagliptin. The primary efficacy endpoint was the percentage of patients who attained HbA1c level <7 % at week 24. Vildagliptin significantly increased the percentage of patients who attained HbA1c level <7 %. It was significantly higher in patients with lower baseline HbA1c, higher C-peptide immunoreactivity (CPR) index [plasma CPR (ng/ml)/glucose (mg/dl) × 100], and in patients whose CPR index increased after the administration of vildagliptin. Categorical analyses by age, gender, and body mass index showed no significant differences among categories. There was no significant difference in HbA1c-lowering effect in the categories of oral hypoglycemic agents used concomitantly with vildagliptin, nor of hypoglycemic agents switched to vildagliptin. Logistic regression analyses indicated that the only factor contributing to the glucose-lowering effect of vildagliptin was baseline HbA1c. There were no changes in clinical parameters thought to be adverse events. Administration of vildagliptin provided a significant and clinically relevant HbA1c-lowering effect irrespective of age, gender, BMI, and concomitantly or previously used hypoglycemic agents. Furthermore, not only high baseline CPR index, but also the increase in CPR index may be associated with the efficacy of this medication.

Oral glucose-stimulated serum C-peptide predicts successful switching from insulin therapy to liraglutide monotherapy in Japanese patients with type2 diabetes and renal impairment.

In Japan, liraglutide was recently approved for patients with type2 diabetes. To our knowledge, there are no markers predicting successful switching from insulin therapy to liraglutide monotherapy in Japanese patients with type2 diabetes and renal impairment. We therefore assessed clinical characteristics predicting successful switching. We analyzed 21 patients with type2 diabetes and estimated glomerular filtration rates <60mL/min/1.73m(2) receiving long-term insulin in Shiga University of Medical Science Hospital, Otsu, Shiga, Japan. Their β-cell function was assessed by measuring urinary C-peptide and C-peptide immunoreactivity (CPR) index, along with glucagon loading and oral glucose tolerance tests. Blood glucose concentration and blood pressure were measured daily before and after switching from insulin to liraglutide, and glycated hemoglobin (HbA1c; National Glycohemoglobin Standardization Program) was assessed 12weeks after switching to liraglutide. Baseline HbA1c was significantly lower in successfully switched than in unsuccessfully switched patients. CPR index, urinary C-peptide concentration and 6-min post-glucagon increment in CPR (ΔCPR) did not differ significantly in the two groups. ΔCPR 120min after 75g oral glucose was significantly higher in successfully than unsuccessfully switched patients. Mean blood glucose concentrations before breakfast, after breakfast, before lunch and after dinner were significantly lower in successfully switched patients. HbA1c did not change significantly in either group. Measurement of oral glucose-stimulated ΔCPR120min is recommended when considering switching Japanese type2 diabetes patients with renal impairment from insulin to liraglutide monotherapy.

Lower beta cell function relates to sustained higher glycated albumin to glycated hemoglobin ratio in Japanese patients with type 2 diabetes

The aim of this study was to clarify the relationship between baseline beta cell function and future glycated albumin (GA) to glycated hemoglobin ratio (GA/HbA1c) in patients with type 2 diabetes. In our retrospective cohort, 210 type 2 diabetic patients who had been admitted to our hospital and in whom HbA1c and GA had been measured at baseline and 2 years after admission were included in this study. Baseline beta cell function was assessed by postprandial C-peptide immunoreactivity index (PCPRI) during admission. With intensification of treatment during admission, HbA1c and GA were significantly decreased 1 year and 2 years after admission. While baseline HbA1c was not significantly correlated with HbA1c after 2 years, baseline GA/HbA1c was strongly correlated with GA/HbA1c after 2 years (r = 0.575, P <0.001). When the patients were divided into two groups according to median PCPRI, patients with low PCPRI showed higher GA/HbA1c both at baseline and after 2 years compared to those with high PCPRI. There was a significant negative correlation between PCPRI and GA/HbA1c after 2 years (r = -0.379, P <0.001). Multiple regression analysis revealed that PCPRI was an independent predictor of GA/HbA1c after 2 years. In conclusion, our findings suggest that lower beta cell function is associated with sustained higher GA/HbA1c ratio in patients with type 2 diabetes.

Factors associated with glycemic variability in Japanese patients with diabetes

The aim of this study was to clarify determinants of glycemic variability in Japanese patients with diabetes. We performed continuous glucose monitoring (CGM) for 2–4 days in 88 patients with diabetes admitted to our hospital for poor glycemic control (20 with type 1 and 68 with type 2 diabetes). Glycemic variability was assessed by standard deviation (SD) of glucose and mean amplitude of glycemic excursions (MAGE) calculated from CGM data, and its relations to clinical parameters were investigated. Beta-cell function was assessed by serum C-peptide immunoreactivity (CPR) to glucose ratio (CPR index). As a result, glycemic variability was significantly greater in patients with type 1 diabetes than in those with type 2 diabetes. In all patients, the glycated albumin to HbA1c ratio (GA/HbA1c) was positively correlated and the postprandial CPR index was negatively correlated with SD and MAGE (both p < 0.05). In patients with type 2 diabetes, age, diabetes duration, and GA/HbA1c were significantly positively correlated with SD and MAGE, while multivariate analysis suggested that age and diabetes duration are the major determinants of glycemic variability. In conclusion, while glycemic variability was greater in patients with type 1 diabetes than those with type 2 diabetes, age, diabetes duration, GA/HbA1c, and beta-cell function were associated with glycemic variability in Japanese patients with diabetes.

Association between beta cell function and future glycemic control in patients with type 2 diabetes

The aim of this study was to clarify the association between C-peptide immunoreactivity (CPR), a marker of beta cell function, and future glycemic control in patients with type 2 diabetes. We conducted a retrospective analysis of 513 consecutive patients with type 2 diabetes who were admitted to our hospital between 2000 and 2007 and followed up for 2 years. Serum and urinary CPR levels were measured during admission, and CPR index was calculated as the ratio of CPR to plasma glucose. The associations between these markers at baseline and glycemic control after 2 years were assessed by means of logistic regression models. After 2 years, 167 patients (32.6%) showed good glycemic control (HbA1c <6.9%). Baseline serum and urinary CPR indices were significantly associated with good glycemic control after 2 years, and the postprandial CPR to plasma glucose ratio (postprandial CPR index) showed the strongest association (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.12-1.50, P = 0.001) among CPR indices. Multivariate analyses showed consistent results (OR 1.23, 95%CI 1.03-1.48, P = 0.021). In conclusion, preserved beta cell function at baseline was associated with better glycemic control thereafter in patients with type 2 diabetes.

Postprandial serum C-peptide to plasma glucose ratio predicts future insulin therapy in Japanese patients with type 2 diabetes

Type 2 diabetes is a progressive disease, and most patients with type 2 diabetes eventually need insulin therapy to maintain glycemic control. Recent studies have shown that early insulin treatment improved beta cell function as well as insulin resistance in patients with type 2 diabetes[1], suggesting that early introduction of insulin treatment may delay disease progression and be able to maintain good glycemic control thereafter. However, since predictive biomarkers for future insulin therapy have not been established, the introduction of insulin treatment is often delayed in clinical settings [2]. We have recently reported that lower 2 h postprandial C-peptide immunoreactivity (CPR) to plasma glucose ratio (postprandial CPR index; PCPRI) was associated with subsequent need for insulin treatment in Japanese subjects with type 2 diabetes who were admitted to our hospital between 2000 and 2007 [3]. In that study, however, since most patients were started on insulin treatment during the baseline admission, the time-to-event relationship of insulin initiation could not be accounted for in the analysis. Here, we report a sub analysis of this cohort in whom insulin therapy had not been introduced at baseline (N = 190), to establish the predictive value of PCPRI for future insulin therapy using univariate and multivariate Cox proportional hazard models. In addition, the prognostic performance of PCPRI was estimated using receiver operating characteristic (ROC) curve analysis. Baseline characteristics of the subjects were as follows; male 57.9 %, age 65 ± 13 years (mean ± SD), duration of diabetes 10 ± 9 years, BMI 25.3 ± 4.7, HbA1c 9.5 ± 1.8 % (80 ± 20 mmol/mol), fasting CPR 2.14 ± 0.95 ng/ml, fasting CPRI 1.56 ± 0.74, PCPR 5.62 ± 2.59 ng/ml, PCPRI 2.72 ± 1.62 and urinary CPR 78.4 ± 54.7 lg/day. Of the subjects, 52.1 % were treated with a sulfonylurea at baseline. During the observation period (mean 4.2 ± 2.3 years, median 3.0 years), insulin therapy was introduced in 34 subjects (18 %). Higher PCPRI at baseline was associated with a lower risk of future insulin therapy (hazard ratio (HR) for 1 unit increase in PCPRI was 0.48, 95 % CI: 0.32 to 0.73, P \ 0.001). However, neither fasting CPRI nor urinary CPR predicted future insulin therapy (P = 0.30 and P = 0.72, respectively). After adjustment for age, sex, duration of diabetes, family history of diabetes, BMI, HbA1c and sulfonylurea use at baseline, PCPRI remained an independent predictor of future insulin therapy (HR = 0.42, 95 % CI: 0.25 to 0.70, P = 0.001). The optimal cutoff value of PCPRI for predicting insulin therapy was 2.16, with 70.6 % sensitivity and 64.1 % specificity (area under the curve (AUC) of ROC curve = 0.698, 95 % CI: 0.609 to 0.788, P \ 0.001). In the present study, PCPRI predicted future insulin therapy in patients with type 2 diabetes. Interestingly, neither fasting CPR index nor urinary CPR was significantly associated with future insulin therapy, suggesting that PCPRI is the superior marker for future insulin therapy Communicated by Renato Lauro.

Effect of obesity on declining beta cell function after diagnosis of type 2 diabetes: a possible link suggested by cross-sectional analysis

It has been reported that beta cell function progressively declines in patients with type 2 diabetes. The objective of this study was to assess the effect of obesity on declining beta cell function after diagnosis of type 2 diabetes. We conducted a cross-sectional study of 689 consecutive subjects with type 2 diabetes who were admitted to our hospital from 2000 to 2007. Fasting and postprandial serum C-peptide immunoreactivity (CPR) and urinary CPR levels had been measured during admission. The subjects were stratified according to BMI and time since diagnosis. CPR index was calculated as CPR (ng/mL) / plasma glucose (mg/dL) x 100. All CPR measurements were significantly higher in the 263 obese (BMI ≥25) subjects compared to the 426 lean subjects (BMI <25). There was a significant negative correlation between CPR indices and duration of diabetes, suggesting a progressive decline in beta cell function after diagnosis of type 2 diabetes. However, this decline was more apparent in obese subjects (postprandial CPR index 0.059/year) compared to lean subjects (0.025/year). The significant difference in serum CPR indices between the lean and obese subjects was lost in subjects more than 10 years after diagnosis. In conclusion, our observations suggest that beta cell function shows a greater progressive decline in obese subjects than in lean subjects with type 2 diabetes. Treatment of obesity may be an important strategy to preserve beta cell function in patients with type 2 diabetes.