C-peptide Immunoreactivity Levels Research Articles

Analysis of thyroid autoantibodies and the risk of insulin depletion after the clinical onset of acute-onset type 1 diabetes in Japanese patients: the TIDE-J study.

Type 1 diabetes is often accompanied by autoimmune thyroid disease. We aimed to investigate the clinical characteristics of Japanese patients with acute-onset type 1 diabetes and thyroid autoantibodies, focusing on decreased endogenous insulin secretion. We examined 80 patients with acute-onset type 1 diabetes, classifying them into two groups with and without thyroid autoantibodies and compared the clinical characteristics of the two groups. A fasting serum C-peptide immunoreactivity (CPR) of less than 0.1ng/mL was defined as insulin depletion. In patients with thyroid autoantibodies, the median fasting serum CPR levels at the fourth year after the onset of type 1 diabetes were significantly lower than in those without thyroid autoantibodies (p = 0.02). The cumulative incidence of insulin depletion at 5years of duration after diagnosis of type 1 diabetes was significantly higher in thyroid autoantibody-positive group than in thyroid autoantibody-negative group (p = 0.01). In the Cox proportional models adjusted for selected baseline factors (age, sex, and BMI), the presence of thyroid autoantibodies did not increase the risk of insulin depletion within 5years after the onset. However, in bivariate Cox proportional hazards models that investigated the association between thyroid autoantibodies and each baseline factor, the presence of thyroid autoantibodies significantly increased the risk of insulin depletion. Our study showed that Japanese patients with acute-onset type 1 diabetes and positive for thyroid autoantibodies had a higher risk of insulin deficiency within 5years after the onset than those without thyroid autoantibodies.

Coinheritance of HNF1A and glucokinase variants in maturity-onset diabetes of the young.

Maturity-onset diabetes of the young (MODY) is a group of monogenic forms of diabetes mellitus characterized by early-onset diabetes with dominant inheritance of beta-cell dysfunction. There are few reports of the coinheritance of glucokinase (GCK) and hepatocyte nuclear factor 1 alpha gene (HNF1A) variants underlying MODY in patients. Herein, we describe a case involving combinations of monoallelic GCK and HNF1A variants associated with MODY. A 10-year-old Japanese girl with a three-generation family history of diabetes without obesity showed high levels of urinary glucose during a school screening test. Her glucose metabolism profile revealed 124 mg/dL of fasting glucose, 6.9% glycated hemoglobin (HbA1c), and 2.78 ng/mL of C-peptide immunoreactivity levels. In a 75-g oral glucose tolerance test, her base glucose, peak glucose, insulin resistance, and homeostasis model assessment of beta cell function levels were 124 mg/dL, 210 mg/dL (120 min), 1.71, and 33%, respectively. Based on the clinical phenotype of GCK-MODY, alimentary and exercise therapy without oral hypoglycemic agents were used to maintain her fasting glucose and HbA1c levels. We explored the coinheritance of MODY with GCK and HNF1A variants in this and past cases and found that careful clinical follow-up is required to firmly establish phenotypic features. Moreover, the accumulation of data on genetically confirmed MODY associated with the coinheritance of GCK and HNF1A variants will be useful for understanding genotype-phenotype correlations. MODY is a group of monogenic forms of diabetes mellitus characterized by early-onset diabetes with the dominant inheritance of beta-cell dysfunction. MODY2 and MODY3 caused by heterozygous loss-of-function variants in the glucokinase (GCK) and hepatocyte nuclear factor 1 alpha (HNF1A) genes, respectively, are the most common forms of the disease. Few cases of MODY have previously been reported as being associated with the coinheritance of GCK and HNF1A variants. Careful clinical follow-up is required to firmly establish phenotypic features in the coinheritance of MODY with GCK and HNF1A variants. The accumulation of data on genetically confirmed MODY associated with the coinheritance of GCK and HNF1A variants will be useful for understanding genotype-phenotype correlations.

Lipid droplet accumulation in β cells in patients with type 2 diabetes is associated with insulin resistance, hyperglycemia and β cell dysfunction involving decreased insulin granules.

Background and objectivePancreatic fat is a form of ectopic fat. Lipid droplets (LDs) are also observed in β cells; however, the pathophysiological significance, especially for β cell function, has not been elucidated. Our aim was to assess LD accumulation in β cells in various stages of glucose intolerance and to clarify its relationship with clinical and histological parameters.MethodsWe examined 42 Japanese patients who underwent pancreatectomy. The BODIPY493/503-positive (BODIPY-positive) area in β cells was measured in pancreatic sections from 32 patients. The insulin granule numbers were counted in an additional 10 patients using electron microscopy.ResultsThe BODIPY-positive area in β cells in preexisting type 2 diabetes patients was higher than that in normal glucose tolerance patients (p = 0.031). The BODIPY-positive area in β cells was positively correlated with age (r = 0.45, p = 0.0097), HbA1c (r = 0.38, p = 0.0302), fasting plasma glucose (r = 0.37, p = 0.045), and homeostasis model assessment insulin resistance (r = 0.41, p = 0.049) and negatively correlated with an increase in the C-peptide immunoreactivity level by the glucagon test (r = -0.59, p = 0.018). The ratio of mature insulin granule number to total insulin granule number was reduced in the patients with rich LD accumulation in β cells (p = 0.039).ConclusionsType 2 diabetes patients had high LD accumulation in β cells, which was associated with insulin resistance, hyperglycemia, aging and β cell dysfunction involving decreased mature insulin granules.

Relation between the insulin lowering rate and changes in bone mineral density: Analysis among subtypes of type 1 diabetes mellitus.

Aims/IntroductionThe bone mineral density in patients with type 1 diabetes mellitus is reduced due to impaired insulin secretion. However, it is unclear whether the rate of bone mineral density reduction is affected by the type 1 diabetes mellitus subtype. This study aimed to clarify the difference in bone mineral density across type 1 diabetes mellitus subtypes: slowly progressive (SP), acute‐onset (AO), and fulminant (F).MethodsThis was a retrospective, single‐center, cross‐sectional study conducted on 98 adult type 1 diabetes mellitus patients. The main outcome included the bone mineral density Z‐score (BMD‐Z) measured at the lumbar spine and femoral neck.ResultsThe lumbar spine BMD‐Z was lower in the acute‐onset than in the slowly progressive subtype (P = 0.03). No differences were observed when compared with the fulminant subtype. The femoral neck BMD‐Z tended to be higher in the slowly progressive than in the acute‐onset and fulminant subtypes. Multiple regression analyses showed that the lumbar spine BMD‐Z was associated with subtypes (AO vs SP) (P = 0.01), but not subtypes (F vs SP), adjusted for sex, duration, retinopathy, and C‐peptide immunoreactivity (CPR). When the patients were divided into disease duration tertiles, in the first and second tertiles, the CPR levels were lower in the acute‐onset or fulminant than in the slowly progressive subtype. In contrast, the lumbar spine and femoral neck BMD‐Z differed between the acute‐onset and slowly progressive only in the second tertiles (both P < 0.01), with a similar tendency between the fulminant and slowly progressive subtypes.ConclusionsAmong the type 1 diabetes mellitus subtypes, bone mineral density undergoes time‐dependent changes, which reveals that the bone mineral density decline follows the impaired insulin secretion. These results provide novel insights into the association between the low insulin exposure duration and bone mineral density.

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.

Residual endogenous insulin secretion in Japanese children with type 1A diabetes.

.We investigated serum C-peptide immunoreactivity (CPR) levels in registered data from a multi-center collaborative nationwide type 1 diabetes study. The CPR levels were obtained from 576 and 409 children during the early registration (2013/2014) and late observation (2016/2017) periods, respectively. The percentages of children with a CPR < 0.1 or < 0.3 ng/mL increased according to the duration since diagnosis. Among patients with 5 or more years since diagnosis, 69% had a CPR < 0.1 and 95% had a CPR < 0.3 in the early registration period. A significant negative correlation was observed between the HbA1c and the CPR levels, and the HbA1c levels were significantly higher among children with a CPR < 0.1 or < 0.3 than among those with a CPR ≥ 0.6 ng/mL. During the late observation period, the prevalence of a CPR < 0.1 ng/mL was 88% among long-standing patients and 77% among patients aged 18–20 yr. Regarding the characteristics of “Responders” with a sustained CPR ≥ 0.6 ng/mL at 5 or more years since diagnosis, six of the seven were adolescent females; five of the seven had an HLA DR4-DQ4 haplotype. When type 1A diabetes mellitus (T1AD) children transit to adult care centers, most of them may have some difficulty in glycemic control because of the depleted endogenous insulin.

Clinical Utility of the Meal Tolerance Test in the Care of Patients with Type 2 Diabetes Mellitus.

Objective The measurement of C-peptide immunoreactivity (CPR) is essential for evaluating the pancreatic β-cell function and selecting appropriate therapeutic agents in patients with diabetes mellitus. The meal tolerance test (MTT) is simple to administer physiological insulin-stimulating test. Previous studies have reported that several CPR-related indices are useful markers for predicting insulin requirement in type 2 diabetes. In the present study, we investigated the serum CPR response during the MTT in hospitalized patients with type 2 diabetes mellitus in order to clarify the clinical utility of the MTT. Methods We performed the MTT using a test meal with timed measurements of the serum CPR level based on the oral glucose tolerance test over 180 minutes and tested the correlation of various CPR-related indices and clinical factors in patients with type 2 diabetes mellitus. Patients The subjects were patients with type 2 diabetes mellitus who had been admitted to our hospital for diabetes management and education. The final study population consisted of 68 patients. Results The fasting CPR level was correlated with the 24-hour urinary CPR excretion and body mass index. The serum CPR level at 120 minutes in the MTT was strongly correlated with the area under the curve of CPR during the MTT. The patients who needed insulin therapy at 6 months after hospitalization showed a significant lower incremental CPR value from 0 to 120 minutes in the MTT than those who did not need insulin therapy. Conclusion The plasma C-peptide levels at 0 and 120 minutes in the MTT provide essential information for the clinical management of patients with type 2 diabetes mellitus.

Effect of High β-glucan Barley on Postprandial Blood Glucose and Insulin Levels in Type 2 Diabetic Patients

The aim of our study was to investigate whether high β-glucan-containing barley (7.2 g per 100 g) improves postprandial plasma glucose levels and suppresses postprandial insulin levels during a meal tolerance test in type 2 diabetic patients. A meal tolerance test (500 kcal) was conducted using two types of test meals: a test meal with white rice (WR) alone (WR diet) and a test meal with WR mixed with 50% barley (BR diet) as staple food. The side dish was the same in the both meals. The changes in plasma glucose and serum C-peptide immunoreactivity (CPR) levels for 180 minutes after ingestion of the test meals were compared. Ten patients with type 2 diabetes (age 52.5 ± 15.1 years, and 7 males and 3 females) were included in this study. The mean HbA1c level and body mass index were 8.8 ± 1.4%, and 29.7 ± 4.5 kg/m2, respectively. Plasma glucose levels after ingestion of the WR diet or BR diet peaked at 60 minutes, which showed no significant differences between the two types of test meals. However, the incremental area under the curve (IAUC) of plasma glucose levels after ingestion of BR diet was significantly lower than that of WR diet. The serum CPR levels at 180 min and their IAUC over 180 minutes after ingestion of BR diet were significantly lower than those of WR diet. Conclusion: Increase in postprandial plasma glucose and insulin levels was suppressed by mixing high-β-glucan barley with WR in type 2 diabetic patients.

Characteristics of factors for decreased lung function in elderly patients with type 2 diabetes

Chronic obstructive pulmonary disease (COPD) often accompanies type 2 diabetes mellitus (T2DM). However, background factors affecting these diseases in the elderly remain unclear. Eligible patients with T2DM were divided into two age groups—non-elderly (<65 years) and elderly (≥65 years); COPD, ratio of forced expiratory volume in one second to forced expiratory volume (FEV1/FVC ratio), and percent predicted forced expiratory volume in one second (FEV1% predicted) were examined, and factors related to reduced respiratory function according to age group were evaluated. In total, 371 patients with T2DM were analysed. COPD was found in 9 patients (5.3%) in the non-elderly group and 45 (22.5%) in the elderly group. In the elderly, male sex, low body mass index (BMI), insulin therapy, and high C-peptide immunoreactivity levels were factors related to COPD. In the non-elderly, age, female sex, high BMI were factors related to decreased FEV1% predicted. Female sex was factor related to decreased FEV1% predicted in both age groups. Low BMI was a factor related to reduced respiratory function in elderly patients and high BMI was a factor related to reduced respiratory function in non-elderly patients. Thus, BMI needs to be managed according to the age and general condition of T2DM patients.

Characteristics and clinical course of type 1 diabetes mellitus related to anti-programmed cell death-1 therapy.

We conducted a national survey to clarify the characteristics and clinical course of type 1 diabetes related to anti-programmed cell death-1 therapy. We analyzed the detailed data of 22 patients that were collected using a Japan Diabetes Society survey and a literature database search. Among the 22 patients, 11 (50.0%) met the criteria for fulminant type 1 diabetes and 11 (50.0%) met the criteria for acute-onset type 1 diabetes. The average patient age was 63years. The mean duration between the date of the first anti-PD-1 antibody injection and development of type 1 diabetes was 155days and ranged from 13 to 504days. Flu-like symptoms, abdominal symptoms, and drowsiness were observed in 27.8, 31.6, and 16.7% patients, respectively. Mean ±standard deviation or median (first quartile-third quartile)glucose levels, HbA1c levels, urinary C-peptide immunoreactivity levels, and fasting serum C-peptide immunoreactivity levels were 617 ± 248mg/dl, 8.1 ± 1.3%, 4.1 (1.4-9.4) μg/day, and 0.46 (0.20-0.70) ng/ml, respectively. Seventeen of 20 patients (85.0%) developed ketosis, and 7 of 18 patients (38.9%) developed diabetic ketoacidosis. Ten of 19 patients (52.6%) showed at least one elevated pancreatic enzyme level at the onset and two of seven patients showed this elevation before diabetes onset. Only one of 21 patients was anti-glutamic acid decarboxylase antibody positive. Anti-programmed cell death-1 antibody-related type 1 diabetes varies from typical fulminant type 1 diabetes to acute-onset type 1 diabetes. However, diabetic ketoacidosis was frequently observed at the onset of diabetes. An appropriate diagnosis and treatment should be provided to avoid life-threatening metabolic alterations.

Effects of isomaltulose on insulin resistance and metabolites in patients with non‑alcoholic fatty liver disease: A metabolomic analysis.

Insulin resistance is associated with a poor prognosis in non-alcoholic fatty liver disease (NAFLD) patients. Isomaltulose, a naturally-occurring disaccharide, is reported to improve glucose and lipid metabolisms in obese patients. The present study aimed to investigate the effects of isomaltulose on insulin resistance and various metabolites in NAFLD patients. Five male patients with NAFLD consumed 20 g isomaltulose or sucrose (control). Changes in insulin resistance and metabolites were evaluated by alterations of serum C-peptide immunoreactivity (CPR) and metabolomic analysis from baseline to 15 min after the administration, respectively. There was no significant difference in changes of blood glucose level; however, the CPR level was significantly decreased in the Isomaltulose group compared to the control group (0.94±0.89 vs. −0.12±0.31, P=0.0216). In a metabolomic analysis, a significant alteration was seen in 52 metabolites between the control and Isomaltulose groups. In particular, the taurodeoxycholic acid level significantly increased approximately 12.5-fold, and the arachidonic acid level significantly decreased approximately 0.01-fold. Together, it present study demonstrated that isomaltulose improved insulin resistance in NAFLD patients. It was also revealed that isomaltulose affects taurodeoxycholic acid and arachidonic acid. Thus, isomaltulose may have a beneficial effect on insulin resistance through alterations of bile acid and fatty acid metabolisms in NAFLD patients.

O4-2 - A Case of Fulminant Type 1 Diabetes Mellitus Induced Takotubo Cardiomyopathy

A 64 years old female patient had admitted to our hospital because of uncosciousness. One week before the admission, she had a fever and abdominal pain. The blood examination by her home doctor revealed slight increase of plasma amylase. Following these symptoms, she had unconsciousness and diabetic ketoacidosis, and the patient was transferred to our hospital. The plasma glucose level was 871 mg/dl and HbA1c was 7.0%. Blood gas analysis showed a pH of 7.067. The plasma and urine levels of C-peptide immunoreactivity (CPR) was 0.1 ng/ml and under 1.8 ug/day, respectively. The second day of admission, the electrocardiogram revealed ST elevation concomitant with increase creatine kinase and troponin I. The coronary angiography showed no coronary stenosis and left ventriculography revealed hypokinesis in apex lesion. To observe the pancreatic endocrine secretion, glucagon stimulation test was done. Blood sampling of CPR at 6 min after glucagon bolus intravenous administration was 0.1 ng/ml, indicating that insulin secretion was abolished. Both of anti GAD antibody and anti-IA-2 autoantibody were negative. Based on the results, this patient suffered a fulminant type 1 diabetes mellitus with takotubo cardiomyopathy. Takotubo cardiomyopathy is known as stress induced cardiomyopathy. Fulminant type 1 diabetes is a non-autoimmune disorder characterized by sudden onset. We report that fulminant type 1 diabetes mellitus is considered as one of cause for Takotubo cardiomyopathy.

Efficacy of dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2 diabetes undergoing hemodialysis.

BackgroundIncretin therapy is feasible in patients with type 2 diabetes mellitus undergoing hemodialysis (HD). However, few studies have examined the safety and efficacy of this therapeutic approach in patients with diabetes and renal impairment. Here, we examined glycemic control and the anti-oxidative-stress effects of the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin in patients with type 2 diabetes undergoing HD.MethodsThirty-five patients with type 2 diabetes undergoing HD (including 13 insulin-treated patients) were switched from ongoing therapy to linagliptin (5 mg, once daily). Levels of fasting blood glucose, C-peptide immunoreactivity (CPR), glycated albumin, B-type natriuretic peptide, oxidized low-density lipoprotein (oxLDL), high-sensitivity C-reactive protein, 8-hydroxy-2′-deoxyguanosine (8OHdG), body mass index, blood pressure, and other biologic characteristics (liver function, renal function, lipid profile) were determined before and 3 months after linagliptin treatment. Patients were classified into insulin-treated and non-insulin groups.ResultsWith the exception of levels of total bilirubin, aspartate aminotransferase, and CPR, none of the patients exhibited changes in glucose metabolism after switching to linagliptin treatment. However, oxLDL levels were decreased significantly by linagliptin therapy in the non-insulin-treated group despite the absence of changes in glycemic control.ConclusionLinagliptin can decrease serum levels of oxLDL in patients with type 2 diabetes undergoing HD independent of its glucose-lowering effect.

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.

Increment of serum C-peptide measured by glucagon test closely correlates with human relative beta-cell area.

Pancreatic beta-cell mass contributes to glucose tolerance. The aim of this study was to evaluate the relationships between human beta-cell mass and various clinical parameters, including insulin secretory capacity. The study included 32 Japanese patients who underwent pancreatectomy and were naive to oral hypoglycemic agents and insulin. They were classified into those with normal glucose tolerance (n=13), impaired glucose tolerance (n=9) and diabetes (n=10), and their insulin secretory capacity and insulin resistance were evaluated. Immunohistochemistry was used to determine relative beta-cell area (%) which represented the proportion of insulin-positive cell area to whole pancreatic section. Increment of C-peptide immunoreactivity level by glucagon test (ΔC-peptide, increment of serum C-peptide [nmol/L] at 6 min after intravenous injection of 1-mg glucagon; r=0.64, p=0.002), homeostasis model assessment of beta-cell function (HOMA-beta, fasting immunoreactive insulin [μIU/mL] x 20 / (fasting plasma glucose [mmol/L] - 3.5); r=0.50, p=0.003), C-peptide index (CPI, fasting C-peptide [nmol/L] / fasting plasma glucose [mmol/L]; r=0.36, p=0.042), and fasting immunoreactive insulin (F-IRI [pmol/L]; r=0.36, p=0.044) correlated significantly and positively with the relative beta-cell area. The area under the curve of plasma glucose level from 0 to 120 min by 75 g-OGTT (AUC0-120) also correlated significantly and inversely with the relative beta-cell area (r=-0.36, p=0.045). Stepwise multiple regression analysis identified ΔC-peptide as the only independent and significant determinant of the relative beta-cell area. We conclude that ΔC-peptide, HOMA-beta, CPI, F-IRI and AUC0-120 correlated closely with the relative beta-cell area, and ΔC-peptide was the most valuable index for the prediction of the area.

Postprandial serum C-peptide value is the optimal index to identify patients with non-obese type 2 diabetes who require multiple daily insulin injection: Analysis of C-peptide values before and after short-term intensive insulin therapy.

Type 2 diabetes is a progressive disease characterized by a yearly decline in insulin secretion; however, no definitive evidence exists showing the relationship between decreased insulin secretion and the need for insulin treatment. To determine the optimal insulin secretory index for identifying patients with non-obese type 2 diabetes who require multiple daily insulin injection (MDI), we evaluated various serum C-peptide immunoreactivity (CPR) values. We near-normalized blood glucose with intensive insulin therapy (IIT) over a 2-week period in 291 patients with non-obese type 2 diabetes, based on our treatment protocol. After improving hyperglycemia, we challenged with oral hypoglycemic agent (OHA), and according to the responsiveness to OHA, patients were classified into three therapy groups: OHA alone (n=103), basal insulin plus OHA (basal insulin-supported oral therapy [BOT]; n=56) and MDI (n=132). Glucagon-loading CPR increment (ΔCPR), fasting CPR (FCPR), CPR 2h after breakfast (CPR2h), the ratio of FCPR to FPG (CPI), CPI 2h after breakfast (CPI2h) and secretory unit of islets in transplantation (SUIT) were submitted for the analyses. Receiver operating characteristic (ROC) and multiple logistic analyses for these CPR indices were carried out. Many CPR values were significantly lower in the MDI group compared with the OHA alone or BOT groups. ROC and multiple logistic analyses disclosed that post-prandial CPR indices (CPR2h and CPI2h) were the most reliable CPR markers to identify patients requiring MDI. Postprandial CPR level after breakfast is the most useful index for identifying patients with non-obese type 2 diabetes who require MDI therapy.

Effects of short-term intensive glycemic control on insulin, glucagon, and glucagon-like peptide-1 secretion in patients with Type 2 diabetes.

Short-term intensive insulin therapy (IIT) in patients with Type 2 diabetes mellitus (T2DM) has beneficial effects on insulin secretion. However, IIT effect on glucagon and glucagon-like peptide-1 (GLP-1) secretion is unknown. We evaluated short-term intensive glycemic control effects on insulin, glucagon, and GLP-1 secretory dynamics in T2DM. Twenty-six patients with T2DM were hospitalized and treated with IIT for 10-14 days. A meal tolerance test was performed before and after IIT and the differences in serum immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) as well as plasma glucagon and active GLP-1 levels were evaluated. Glycoalbumin levels decreased significantly from 23.0% before to 19.6% after IIT (p<0.001). However, pre- and post-IIT, IRI and CPR levels were not significantly different; post-IIT glucose levels were significantly decreased. The post-IIT glucagon levels at 0 and 60 min were lower than pre-IIT levels. Moreover, post- IIT area under the curve (AUC) of glucagon significantly reduced from 6755 ± 996 pg/dl · 60 min to 5796 ± 1074 pg/dl · 60 min (p<0.001). Furthermore, post-IIT GLP-1 levels and AUC were significantly higher than pre-IIT values. Our results suggest that patients with T2DM who received shortterm IIT demonstrated decreased postprandial glucagon levels and increased GLP-1 levels following a meal tolerance test.

Slowly Progressive Type 1 Diabetes Treated with Metformin for Five Years after Onset

A 52-year-old man was diagnosed with slowly progressive type 1 diabetes (SPIDDM). We expected him to quickly progress to an insulin-dependent state due to a high anti-glutamic acid decarboxylase antibody titer (23.9 U/mL). At SPIDDM diagnosis, he was in a non-insulin-dependent state, with a fasting serum C-peptide immunoreactivity level of 2.5 ng/mL. Therefore, we prescribed metformin. His glycemic control remained stable, and his intrinsic insulin secretion capacity was maintained for five years. Although one case is insufficient to draw firm conclusions, this report suggests that metformin is a therapeutic choice for SPIDDM when the insulin secretion capacity is maintained.

Evaluation of Insulin Secretion and Sensitivity in a Patient with Slowly Progressive Type 1 Diabetes Mellitus

We herein report the case of a patient with slowly progressive type 1 diabetes and insulin independence lasting for >10 years despite the detection of continuously elevated glutamic acid decarboxylase autoantibody titers. We monitored the patient's clinical course and analyzed his endogenous insulin secretion and sensitivity using an intravenous glucose tolerance test (IVGTT) and oral glucose tolerance test (OGTT). His body mass index remained at approximately 22, while his serum C-peptide immunoreactivity level gradually decreased. The level of insulin secretion was significantly higher on the OGTT than the IVGTT. The patient's insulin sensitivity was within the normal limits. These results suggest that maintaining a lifestyle sufficient to preserve insulin secretion and/or normal insulin sensitivity is important and that β-cell responsiveness to incretins may, in part, contribute to insulin independence.

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.