Fasting Plasma C-peptide Levels Research Articles

U-shaped association between plasma C-peptide and sarcopenia: A cross-sectional study of elderly Chinese patients with diabetes mellitus.

Limited research exists regarding the relationship between fasting plasma C-peptide levels and sarcopenia. As a result, our study aimed to examine this association in elderly Chinese diabetic patients. This cross-sectional study included 288 elderly patients with diabetes mellitus from the Fourth People's Hospital in Guiyang who were enrolled prospectively between March 2020 and February 2023. The independent variable of interest was fasting plasma C-peptide, while the dependent variable was sarcopenia. Data on several covariates, including demographic factors, lifestyle habits, co-morbidities, anthropometric indicators, and laboratory indicators, were also collected. Of the 288 participants, 27.43% (79/288) had sarcopenia. After adjusting for potential confounding variables, we found a U-shaped association between fasting plasma C-peptide levels and sarcopenia, with inflection points identified at approximately 774 pmol/L and 939 mmol/L. Within the range of 50-744 pmol/L, each 100 pmol/L increase in CysC was associated with a 37% decrease in the odds of sarcopenia (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.49 to 0.83; P < 0.001). Additionally, within the range of 939-1694 pmol/L, each 100 pmol/L increase in fasting plasma C-peptide was associated with a 76% increase in the odds of sarcopenia (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.11 to 2.81; P = 0.017). Our study revealed a U-shaped association between fasting plasma C-peptide levels and the likelihood of sarcopenia, with lower risk in the range of 774-939 pmol/L. These findings may assist in the development of more effective prevention and treatment strategies for sarcopenia in elderly diabetic patients.

C-PEPTIDE AS AN INFLAMMATORY MARKER IN OBESE WOMEN.

Insulin resistance (IR) is a component of type 2 diabetes and metabolic syndrome and it increases in the presence of chronic inflammation. Lately, "neutrophil-to-lymphocyte ratio" (NLR) has been used as an indicator of inflammation. This study evaluates the association between IR and NLR in obese women. Obese female patients who were followed up in a university hospital for the last two years were included in the study. Homeostasis model assessment of IR (HOMA-IR), C-peptide, NLR, bioelectrical impedance measurements of 83 patients were analyzed. The C-peptide levels of our patients showed a highly significant correlation with HOMA-IR (p<0.001). A significant positive correlation was found between fasting plasma C-peptide levels and NLR (r=0.36 and p<0.003) in obese women. The increase in C-peptide levels had a significant effect on the increase in NLR (r2=0.31, p=0.002), however insulin had no similar effect on NLR (r2=0.01, p=0.544). Plasma C-peptide levels are better correlated with NLR compared to other parameters of IR. C-peptide may be used as an efficient laboratory marker with high relevance in IR and chronic inflammatory conditions in obese women.

Fasting plasma c-peptide level predicts the response of glucagon-like peptide-1 agonist (exenatide) add on to metformin monotherapy in obese type 2 diabetics

We aimed to evaluate the ability of serum C-peptide levels to predict glycemic control in obese type 2 diabetes (T2DM) patients in which a glucagon-like peptide-1 receptor agonist (GLP1-RA), an exenatide, was added to metformin monotherapy. This was a retrospective study, in which we enrolled 44 consecutives obese, type 2 diabetic patients receiving metformin monotherapy and have inadequate glycemic control (HbA1c &gt;7% and &lt;10%). Twice daily GLP1-RA (10 mcg exenatide injection) was added to the treatment. Weight, height and body mass index (BMI), in addition to fasting plasma glucose, hemoglobin A1c (HbA1c), and C-peptide levels measured baseline and at the sixth months post treatment. Regardless of the initial HbA1c level, treatment success was considered a HbA1c level below 7%. Predictors of successful glycemic control were assessed by a regression analysis. The fasting plasma C-peptide level was used as a marker of β cell function. After adding the GLP-1 RA, fasting glucose, C-peptide, BMI, and body weight decreased significantly (p &lt; 0.01 for all). 27 (61.4%) patients were achieved treatment success, who have HbA1c level &lt; 7% at the sixth month. The baseline C-peptide level was correlated with the HbA1c level 6 months post-treatment (r: 0.4, p: 0.01). Multivariate logistic regression analysis showed that the baseline fasting plasma C-peptide level was an independent predictor of successful glycemic control [exp.B: 6.6 (1.63-26-9) p: 0.008]. In a receiver operating characteristics (ROC) curve analysis, a baseline plasma C-peptide level of 2.56 ng/mL was the best cut-off value. Initial fasting plasma C-peptide levels can predict the treatment response of the GLP1-RA (exenatide 10 mcg, twice daily) add on to metformin monotherapy in obese type 2 diabetics.

1355-P: Carbohydrate Overfeeding Unmasks Severe Dysmetabolic Traits in Low-Birth-Weight Men

Background: Low birth weight (LBW) individuals are at increased risk of developing Type 2 diabetes (T2D) , especially when exposed to an affluent dietary pattern. Impaired subcutaneous adipose tissue expandability and ectopic fat storage may represent key features explaining the link between LBW and risk of T2D. We hypothesized that a 4-week simple carbohydrate overfeeding challenge (+25% energy) (COF) would adversely influence dysmetabolic traits including hepatic fat content in LBW compared to normal birth weight (NBW) men. Methods: Twenty-two non-obese LBW and 21 age- and BMI-matched NBW men with a mean age of 37.6 years were included. Body composition, hepatic fat (MR spectroscopy) , glucose and insulin metabolism, hepatic glucose production (HGP; deuterium glucose) , energy metabolism (indirect calorimetry) and selected plasma biomarkers (multiplex ELISA) were measured before and after 4 weeks COF. Results: Fasting plasma glucose and C-peptide levels, as well as energy expenditure (EE) and fat oxidation (FOX) rates increased significantly more in response to COF among the LBW compared to NBW subjects (all P&amp;lt;0.05) . However, despite significantly increased baseline hepatic fat content, COF resulted in similar body weight and hepatic fat content increments in LBW compared to NBW subjects. HGP and hepatic insulin resistance were unaffected by COF in both groups. Fasting plasma adiponectin levels were significantly reduced in LBW versus NBW subjects before and after COF, whereas plasma leptin and FGF21 levels were increased (both P&amp;lt;0.005) after COF in LBW men only. Conclusion: LBW compared to NBW subjects respond to COF with differential increments in plasma glucose, C-peptide, leptin and FGF21 levels, as well as increased EE and FOX rates. The results underscore the importance of LBW individuals avoiding simple carbohydrate overfeeding. Further studies are needed to understand the role of increased hepatic fat and insulin resistance as key mechanisms linking LBW with increased risk of T2D. Disclosure C.Brøns: Stock/Shareholder; Novo Nordisk. A.B.Thuesen: None. L.Justesen: None. L.Elingaard-larsen: None. J.Størling: None. E.R.Danielsen: None. T.Hansen: None. A.A.Vaag: Stock/Shareholder; AstraZeneca. Funding Novo Nordisk Foundation (NNF15OC0016692) , Aase and Ejnar Danielsens Fond, Augustinus Foundation, Simon Spies Fonden, TrygFonden.

The Role of Lactate Exercise Test and Fasting Plasma C-Peptide Levels in the Diagnosis of Mitochondrial Diabetes: Analysis of Clinical Characteristics of 12 Patients With Mitochondrial Diabetes in a Single Center With Long-Term Follow-Up.

ObjectiveThe aim of this study was to analyze the clinical characteristics and the pattern of long-term changes of fasting plasma C-peptide in patients with mitochondrial diabetes (MD), and to provide guidance for the diagnosis and treatment of MD.MethodsWe retrieved MD patients with long-term follow-up at Peking Union Medical College Hospital from January 2005 to July 2021 through the medical record retrieval system and retrospectively analyzed their clinical data, biochemical parameters, fasting plasma C-peptide, glycosylated hemoglobin and treatment regimens. Non-parametric receiver operating characteristic (ROC) curves were used to assess the relationship between exercise test-related plasma lactate levels and suffering from MD.ResultsA total of 12 MD patients were included, with clinical characteristics of early-onset, normal or low body weight, hearing loss, maternal inheritance, and negative islet-related autoantibodies. In addition, patients with MD exhibited significantly higher mean plasma lactate levels immediately after exercise compared to patients with type 1 diabetes mellitus (T1DM) (8.39 ± 2.75 vs. 3.53 ± 1.47 mmol/L, p=0.003) and delayed recovery time after exercise (6.02 ± 2.65 vs. 2.17 ± 1.27 mmol/L, p=0.011). The optimal cut-off points identified were 5.5 and 3.4 mmol/L for plasma lactate levels immediately after and 30 minutes after exercise, respectively. The fasting plasma C-peptide levels decreased as a negative exponential function with disease progression (Y= 1.343*e-0.07776X, R2 = 0.4154). Treatment regimens in MD patients were varied, with no metformin users and a weak correlation between insulin dosage and body weight.ConclusionsThe increased level of plasma lactate during exercise or its delayed recovery after exercise would contribute to the diagnosis of MD. Changes of fasting plasma C-peptide in MD patients over the course of the disease indicated a rapid decline in the early stages, followed by a gradual slowing rate of decline.

Skeletal status in children and adolescents with new-onset type 1 diabetes: a preliminary study based on bone densitometry and quantitative ultrasound.

Type 1 diabetes (T1D) represents a risk factor for bone loss and impaired bone quality. We conducted an exploratory retrospective cross-sectional study involving youths with new-onset T1D, to investigate the relationship between lumbar spine dual-energy X-ray absorptiometry (DXA) and phalangeal quantitative ultrasound (QUS) measurements, along with their correlation with markers of bone turnover, glucose homeostasis, and residual β-cell function. 17 children and adolescents (8 females) with recent-onset T1D were enrolled into this study. Lumbar spine areal bone mineral density (aBMD) and age-adjusted amplitude-dependent speed of sound (AD-SoS) Z-scores were indicative of low BMD status (≤ -2.0 SD) in 11.7% and 17.6% of participants, respectively. Spearman's correlation analysis revealed significant inverse correlations between AD-SoS values and circulating levels of β-CrossLaps, alkaline phosphatase, and osteocalcin, along with a significant positive correlation between bone transmission time (BTT) values and fasting plasma C-peptide (FCP) levels. There was no statistically significant correlation between DXA-QUS parameters, fasting plasma glucose (FPG), and glycated haemoglobin (HbA1c). Finally, there was a significant positive correlation between lumbar spine aBMD and BTT values. Our study suggests that DXA and/or QUS parameters may be altered in a small proportion of T1D children and adolescents at the disease onset. Additionally, residual β-cell function may represent a protective factor against T1D-related detrimental skeletal changes. Large and long-term prospective studies are needed to confirm these preliminary findings since the present study is limited by the retrospective cross-sectional design and by its small sample size.

The effect of laparoscopic sleeve gastrectomy on type 2 diabetes remission outcomes in patients with body mass index between 25 kg/m 2 and 32.5 kg/m 2

BackgroundThe effect of laparoscopic sleeve gastrectomy (LSG) in the treatment of type 2 diabetes (T2D) patients with body mass index (BMI is calculated by dividing weight in kilograms by height in meters squared) higher than 25 kg/m2 but lower than 32.5 kg/m2, especially in East Asian population characterized by abdominal obesity, are still unclear. This study aims to explore the effect of LSG in T2D patients with BMI higher than 25 kg/m2 but lower than 32.5 kg/m2. MethodsA total of 49 T2D patients with BMI(25–32.5 kg/m2) treated successfully with LSG were included in our study. The effect of LSG on T2D remission outcomes at 12 and 24 months after operation was analyzed. ResultsAll patients were treated successfully with LSG without conversion. The mean preoperative body weight,BMI, fasting plasma glucose, glycosylated hemoglobin (A1c) and fasting C-peptide were 81.7 ± 10.0 kg, 29.1 ± 2.4 kg/m2, 10.4 ± 3.9 mmol/L,8.2 ± 1.5%, and 2.3 ± 1.1 nmol/L,respectively.The age, duration of diabetes and ABCD score were 48.6 ± 9.6 years,6.6 ± 5.1 years, and 2.9 ± 1.5. The mean fasting plasma glucose,A1c, and C-peptide levels were significantly decreased at 12 and 24 months after operation. At postoperative 24 months, 18 out of 49 patients (36.7%) reached diabetes complete remission (A1c levels≤6.0%).14 out of 49 patients (28.6%) reached partial remission (6.0% < A1c levels<6.5%). 8 out of 49 patients (16.3%) reached notable improvement (6.5% < A1c levels<7%). At 24 months after LSG, the complete remission rate of T2D patients with a BMI of 25–27.5 kg/m2 was 35.3%, the complete remission rate of patients with a BMI of 27.5–30 kg/m2 was 11.1%, and the complete remission rate of patients with a BMI of 30–32.5 kg/m2 was 47.8%.At postoperative 24 months, the complete remission rate of T2D patients with ABCD score≤2 was 5.0%, the complete remission rate of patients with ABCD score 3 to 4 was 52.4%, and the complete remission rate of patients with ABCD score≥5 was 75.0%. ConclusionOur study demonstrates that LSG could result in a significant effect on T2D in patients with BMI 30–32.5 kg/m2. In addition, our study indicates that higher ABCD score can predict a better diabetes remission outcome in diabetes patients with BMI ≤32.5 kg/m2.

453-P: Diabetes Knowledge Test Score Predicts HbA1c Levels after Discharge in Inpatients with Type 2 Diabetes

Introduction: Many cross-sectional studies have reported that higher diabetes knowledge test (DKT) scores were associated with better glycemic controls in outpatients with type 2 diabetes. We investigated whether inpatients with high DKT scores could achieve better glycemic control after discharge. Method: This multicenter longitudinal study included 37 inpatients with type 2 diabetes, who had poor glycemic control from October 2018 to November 2019 in Japan. The exclusion criteria were history of stroke, dementia, and psychiatric conditions. The baseline characteristics were HbA1c level, 10.5%±2.5%; median age, 70 y (58-76); median (first to third quartile); diabetes duration, 6 y (1-20); and fasting plasma C-peptide level, 1.4 ng/ml (0.9-2.0 ng/ml). The patients underwent the original DKT at discharge, consisting of 14 items (full score, 14 points). The Cronbach’s α was 0.71. The questions included Q6 “When is a good time to improve the postprandial blood glucose level if you exercise?”, Q11 “How many calories are in 100 g steamed white rice?”, and Q12 “Which beverage is inappropriate during hyperglycemia?” We investigated whether DKT score and baseline characteristics correlated with the HbA1c level at 48 weeks after discharge. Result: The HbA1c level at 48 weeks after discharge was 7.2% (6.3%-7.6%); ΔHbA1c, −2.6 (−4.6 to −1.2); and total DKT score, 10 (6-11). The total DKT score was negatively associated with the HbA1c level at 48 weeks after discharge (Spearman r: −0.26) and ΔHbA1c (r: −0.30). The subjects with shorter diabetes durations and higher ΔCPR showed improved HbA1c levels. The patients who correctly answered Q6, Q11, and Q12 dependently got better HbA1c levels at 48 weeks after discharge compared with those with incorrect answers(p&amp;lt;0.05). Conclusion: The better total DKT score improved HbA1c levels in patients with type 2 diabetes at 48 weeks after discharge. Knowledge of calorie intake and best exercise timing may contribute to better glycemic control. Disclosure K. Okubo: None. T. Minami: None. A. Kameda: None. T. Yamada: None. H. Hiiragi: None. F. Yoshida: None. M. Takahashi: None. Y. Suzuki: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K. K., Novo Nordisk, Sanofi, Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K. K., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Speaker’s Bureau; Self; Abbott, Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K. K., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.

Effects of fitness qigong and tai chi on middle-aged and elderly patients with type 2 diabetes mellitus.

Currently, qigong and tai chi exercises are the two most common preventive as well as therapeutic interventions for chronic metabolic diseases such as type 2 diabetes mellitus (T2DM). However, the quantitative evaluation of these interventions is limited. This study aimed to evaluate the therapeutic efficacy of qigong and tai chi intervention in middle-aged and older adults with T2DM. The study included 103 eligible participants, who were randomized to participate for 12 weeks, in one of the following intervention groups for the treatment of T2DM: fitness qigong, tai chi, and control group. Three biochemical measures, including fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), and C-peptide (C-P) levels, assessed at baseline and 12 weeks, served as the primary outcome measures. During the training process, 16 of the 103 participants dropped out. After the 12-week intervention, there were significant influences on HbA1C (F2,83 = 4.88, p = 0.010) and C-P levels (F2,83 = 3.64, p = 0.031). Moreover, significant reduction in C-P levels was observed after 12-week tai chi practice (p = 0.004). Furthermore, there was a significant negative correlation between the duration of T2DM and the relative changes in FPG levels after qigong intervention, and the relative changes in HbA1C levels were positively correlated with waist-to-height ratio after tai chi practice. Our study suggests that targeted qigong exercise might have a better interventional effect on patients with a longer duration of T2DM, while tai chi might be risky for people with central obesity.Trial registration: This trial was registered in Chinese Clinical Trial Registry. The registration number is ChiCTR180020069. The public title is “Health-care qigong · study for the prescription of chronic diabetes intervention.”

Assessment of functional outcome of patients undergoing surgery for chronic pancreatitis: A prospective study.

Backgrounds/AimsThis study was done with the aim of assessing impact of surgery for chronic pancreatitis on exocrine and endocrine functions, quality of life and pain relief of patients.Methods35 patients of chronic pancreatitis who underwent surgery were included. Exocrine function assessed with fecal fat globule estimation and endocrine function assessed with glycated haemoglobin (HbA1C), fasting plasma glucose (FPG), Insulin and C-peptide levels. Percentage (%) beta cell function by homeostatic model assessment (HOMA) was determined using web-based calculator. Quality of life (QOL) and pain assessment was done using Short form survey (SF-36) questionnaire and Izbicki scores respectively. Follow up done till 3 months following surgery.ResultsEndocrine insufficiency was noted in 13 (37%) patients in the postoperative period compared to 17 (49%) patients preoperatively (p=0.74). Exocrine insufficiency was detected in 11 (32%) patients postoperatively compared to 8 (23%) patients preoperatively, with denovo insufficiency noted in 3 (8%) patients (p<0.05). The mean Izbicki score at 3 months postoperatively was remarkably lower compared to preoperative score (29.3±14.3 vs. 60.6±12.06; p<0.05). QOL at 3 months following surgery for chronic pancreatitis was significantly better than preoperative QOL (50.24±22.16 vs. 69.48±20.81; p<0.05).ConclusionsSignificant pain relief and improvement in quality of life among patients of chronic pancreatitis following surgery. However, worsening of exocrine function with only clinical improvement of endocrine function was also noted.

Circulating Follistatin and Activin A and Their Regulation by Insulin in Obesity and Type 2 Diabetes

Circulating follistatin (Fst) binds activin A and thereby regulates biological functions such as muscle growth and β-cell survival. However, Fst and activin A's implication in metabolic regulation is unclear. To investigate circulating Fst and activin A in obesity and type 2 diabetes (T2D) and determine their association with metabolic parameters. Further, to examine regulation of Fst and activin A by insulin and the influence of obesity and T2D hereon. Plasma Fst and activin A levels were analyzed in obese T2D patients (N = 10) closely matched to glucose-tolerant lean (N = 12) and obese (N = 10) individuals in the fasted state and following a 4-h hyperinsulinemic-euglycemic clamp (40 mU·m-2·min-1) combined with indirect calorimetry. Circulating Fst was ~30% higher in patients with T2D compared with both lean and obese nondiabetic individuals (P < .001), while plasma activin A was unaltered. In the total cohort, fasting plasma Fst correlated positively with fasting plasma glucose, serum insulin and C-peptide levels, homeostasis model assessment of insulin resistance, and hepatic and adipose tissue insulin resistance after adjusting for age, gender and group (all r > 0.47; P < .05). However, in the individual groups these correlations only achieved significance in patients with T2D (not plasma glucose). Acute hyperinsulinemia at euglycemia reduced circulating Fst by ~30% (P < .001) and this response was intact in patients with T2D. Insulin inhibited FST expression in human hepatocytes after 2 h and even further after 48 h. Elevated circulating Fst, but not activin A, is strongly associated with measures of insulin resistance in patients with T2D. However, the ability of insulin to suppress circulating Fst is preserved in T2D.

Diabetes after pancreaticoduodenectomy: can we predict it?

BackgroundThere is limited literature about the perioperative factors which can predict endocrine insufficiency after pancreaticoduodenectomy (PD). The primary aim was to correlate percentage pancreatic remnant volume (%RV) after PD in nondiabetic patients with the development of new-onset impaired glucose tolerance/diabetes mellitus (IGT/DM). The secondary aim was to identify the risk factors for new-onset IGT/DM. MethodsIn this prospective study, all consecutive patients with resectable periampullary carcinoma and without IGT/DM were evaluated with fasting and postprandial plasma glucose, HbA1c, insulin, and C-peptide levels preoperatively and at 3 mo postoperatively. After that, all patients were followed up with fasting and postprandial plasma glucose level assessed at 3-mo intervals for 24 mo or till death, whichever occurred earlier. The %RV was determined from computed tomography measurements preoperatively. ResultsOf the 50 patients, 11 (22%) patients developed IGT/DM after median follow-up of 32 mo. The patients' with/without IGT/DM were similar in demographic/perioperative variables. The %RV was found to be an independent factor associated with new-onset IGT/DM. A %RV of <48.8% was found to be a predictor of new-onset IGT/DM (sensitivity, 89.7%; specificity, 73.6%). Plasma sugar and glycosylated hemoglobin levels were significantly higher postoperatively after PD than the preoperative levels. Insulin and C-peptide levels were significantly lower after PD, irrespective of new-onset IGT/DM. ConclusionsThe incidence of IGT/DM after PD was 22%, and %RV < 48.8% was found to be a significant risk factor for new-onset IGT/DM. (CTRI/2013/12/004233).

Relation of Muscle Indices with Metabolic Parameters and C-Peptide in Type 2 Diabetes Mellitus.

To assess the relation between bioimpedance measurements and metabolic parameters and C-peptide in patient with type 2 diabetes mellitus (DM). Cross-sectional study. Kartal Dr Lutfi Kirdar Training and Research Hospital, Pendik Kaynarca Diabetes Center, Exercise and Metabolism Unit, between January and March 2015. Patients with DM, aged less than 65 years, were assessed for bioimpedance analysis, fasting plasma glucose (FPG), HbA1c, C-peptide levels, triglyceride levels, LDL-cholesterol, and HDL-cholesterol levels. Skeletal muscle index, total muscle index, skeletal muscle percentage, and total muscle percentage were used for muscle-related analyses. Mann-Whitney U-test or independent t-test were used to compare differences between two independent groups. Pearson correlation test or Spearman correlation test were used to find out correlation between variables. Atotal of 359 DM patients were enrolled in the study. Mean age was 51.6 ±8.0 years, and 278 (77.7%) of the participants were females. After adjusting age and gender variables, there was no relation between muscle-related measurements and FPG, triglyceride, LDL-cholesterol (p>0.05). However, there was muscle-related indexes (MRI) positively correlation with C-peptide and inversely associated with HDL-cholesterol (p<0.05). Muscle-related indices positively correlated with C-peptide, which showed endogenous insulin reserve.

A novel mutation in the hepatocyte nuclear factor-1β gene in maturity onset diabetes of the young 5 with multiple renal cysts and pancreas hypogenesis: A case report.

A 17-year-old Chinese male was hospitalized exhibiting hyperglycemia and increased serum urea nitrogen and creatinine levels in addition to weight loss. The patient was treated with gliclazide. The patient was 150 cm tall, weighed 35 kg and had no family history of diabetes or kidney disease. Physical examination revealed cephalus quadratus, rachitic rosary and a visible toe-out gait. Laboratory examinations revealed that the patient's fasting plasma glucose and glycosylated hemoglobin levels were markedly increased, fasting plasma C-peptide level was slightly increased and no peak 2 h postprandial was observed. Diabetic autoimmune antibodies [islet cell cytoplasmic autoantibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), isulinoma-2-associated autoantibodies (IA2A) and insulin autoantibodies (IAA)] were negative. Levels of serum electrolytes decreased, uric acid and parathyroid hormone increased, mild albuminuria was detected and there was a low proportion of urine. The patient also presented with low bone mass and cataracts. Abdominal computed tomography (CT) revealed a bilateral atrophic kidney with multiple renal cysts, primarily located at the junction of renal cortex and medulla, with a diameter of 0.3-0.7 cm. CT also revealed hypogenesis of the body and tail of the pancreas. In an oral glucose tolerance test, the mother and paternal uncle of the patient were diagnosed with type II diabetes and the patient's sister, maternal uncle and paternal grandpa were diagnosed with glucose tolerance impairment. Genetic testing revealed an unreported amino acid mutation in exon 2 of hepatocyte nuclear factor 1β (c.391C>T), a nonsense mutation of CAA to TAA at codon 131. This mutation was identified in the proband but not in any other family members.

A Lanosteryl Triterpene from Protorhus longifolia Improves Glucose Tolerance and Pancreatic Beta Cell Ultrastructure in Type 2 Diabetic Rats.

Type 2 diabetes remains one of the leading causes of death worldwide. Persistent hyperglycemia within a diabetic state is implicated in the generation of oxidative stress and aggravated inflammation that is responsible for accelerated modification of pancreatic beta cell structure. Here we investigated whether a lanosteryl triterpene, methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA-3), isolated from Protorhus longifolia can improve glucose tolerance and pancreatic beta cell ultrastructure by reducing oxidative stress and inflammation in high fat diet and streptozotocin-induced type 2 diabetes in rats. In addition to impaired glucose tolerance, the untreated diabetic rats showed increased fasting plasma glucose and C-peptide levels. These untreated diabetic rats further demonstrated raised cholesterol, interleukin-6 (IL-6), and lipid peroxidation levels as well as a destroyed beta cell ultrastructure. Treatment with RA-3 was as effective as metformin in improving glucose tolerance and antioxidant effect in the diabetic rats. Interestingly, RA-3 displayed a slightly more enhanced effect than metformin in reducing elevated IL-6 levels and in improving beta cell ultrastructure. Although the involved molecular mechanisms remain to be established, RA-3 demonstrates a strong potential to improve pancreatic beta cell ultrastructure by attenuating impaired glucose tolerance, reducing oxidative stress and inflammation.

Preoperative Fasting Plasma C-Peptide Levels as Predictors of Remission of Type 2 Diabetes Mellitus after Bariatric Surgery: A Systematic Review and Meta-Analysis

ABSTRACTAims: The study evaluated the predictive role of preoperative fasting C-peptide, hemoglobin (Hb)A1c, fasting plasma glucose (FPG), and body mass index (BMI) levels on diabetes remission in patients with type 2 diabetes following bariatric surgery. Methods: Medline, PubMed, Central, and Google Scholar databases of up to September 7, 2016 were searched using the following terms: type 2 diabetes mellitus, gastric bypass, Roux-en-Y, anastomosis, C-peptide, weight loss, HbA/HbA1c, predictive/predictor. Results: Meta-analysis of the pooled data indicated that fasting C-peptide was predictive of increased chance of remission of type 2 diabetes (pooled difference in means = 0.93, 95% confidence interval [CI] = 0.61 to 1.25, p < .001). The analysis also found that FPG (pooled standardized mean difference = −0.42, 95% CI: −0.64 to −0.20, p < .004) and HbA1c levels (pooled difference in means = −1.05, 95% CI: −1.48 to −0.62, p < .001) were associated with reduced odds of type 2 diabetes remission. BMI was not found to be associated with remission (pooled difference in means = 0.29, 95% CI: 0.30 to 0.88, p = .343). In general, subgroup analysis, which evaluated the pooled data from the retrospective and prospective studies separately, gave similar results. Conclusions: Preoperative fasting plasma C-peptide was associated with increased type 2 diabetes remission after bariatric surgery, whereas baseline HbA1c and FPG levels were associated with reduced chance of remission. These parameters may be used as a guideline in weighing the risks and benefits for surgical intervention in patients with type 2 diabetes.

Novel non-invasive biological predictive index for liver fibrosis in hepatitis C virus genotype 4 patients.

AIMTo investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy.METHODSA cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensin-converting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance (HOMA-IR).RESULTSFibrosis stages were distributed based on Metavir score as follows: F0 = 43, F1 = 136, F2 = 64, F3 = 45 and F4 = 44. Statistical analysis relied upon reclassification of fibrosis stages into mild fibrosis (F0-F) = 179, moderate fibrosis (F2) = 64, and advanced fibrosis (F3-F4) = 89. Univariate analysis indicated that age, log aspartate amino transaminase, log HOMA-IR and log platelet count were independent predictors of liver fibrosis stage (P < 0.0001). A stepwise multivariate discriminant functional analysis was used to drive a discriminative model for liver fibrosis. Our index used cut-off values of ≥ 0.86 and ≤ -0.31 to diagnose advanced and mild fibrosis, respectively, with receiving operating characteristics of 0.91 and 0.88, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were: 73%, 91%, 75%, 90% and 8.0 respectively for advanced fibrosis, and 67%, 88%, 84%, 70% and 4.9, respectively, for mild fibrosis.CONCLUSIONOur predictive model is easily available and reproducible, and predicted liver fibrosis with acceptable accuracy.

Effects of Sitagliptin on Pancreatic Beta Cell Function and Microangiopathy in Japanese Patients With Type 2 Diabetes Mellitus: Follow-Up for 4 Years

Background: This study was aimed at investigating the effect of long-term sitagliptin treatment in improving the pancreatic beta cell function and its influence on microangiopathy in patients with type 2 diabetes mellitus. Methods: The study was designed as a retrospective analysis of the data of 27 patients with type 2 diabetes mellitus who did not have any evident reduction of the renal function and had received sitagliptin treatment for 4 years or longer. The fasting plasma C-peptide level corrected for the fasting blood glucose level (C-peptide index (CPI)), hemoglobin A1c (HbA1c) and body weight were determined every year during the 4-year period, and the status of retinopathy and nephropathy at the end of the fourth year of sitagliptin treatment was compared with the pre-treatment status. Results: Both the HbA1c and body weight were significantly decreased by 6 months after the start of treatment. Thereafter, the HbA1c showed no further rise during the subsequent 4-year period, while the body weight continued to decrease over the 4-year period. No significant change of the CPI, as compared to the pre-treatment level (0.95 ± 0.49), was observed at any time during the follow-up. The retinopathy and nephropathy remained unchanged in severity in most cases; however, progression of retinopathy was seen in seven cases (29%) and that of nephropathy in three cases (11%). Conclusions: Maintenance of good blood glucose control for 4 years by sitagliptin treatment allowed the pancreatic beta cell function to be preserved. However, it was not possible to suppress progression of microangiopathy completely by treatment for a short period of 4 years. J Endocrinol Metab. 2015;5(4):245-249 doi: http://dx.doi.org/10.14740/jem297w

Conversion From Tacrolimus to Cyclosporine in Patients With New-Onset Diabetes After Renal Transplant: An Open-Label Randomized Prospective Pilot Study

BackgroundNew-onset diabetes after transplant (NODAT) is associated with serious morbidity and mortality. The incidence of NODAT is higher with tacrolimus (Tac) compared with cyclosporine (CsA); however, the effects of switching from Tac to CsA in NODAT have not been studied well. Materials and MethodsThis was a single-center, open-label, prospective, randomized study, including renal transplant recipients who were on Tac-based immunosuppression and developed NODAT. Those with pretransplant diabetes, hypersensitivity to CsA or Tac, severe infections, and denying consent were excluded. Subjects were randomized to either switch to CsA or to continue on Tac. Fasting and postprandial plasma glucose, fasting insulin and C-peptide levels, insulin and oral hypoglycaemic agents (OHA) use were monitored monthly for 3 months, whereas glycosylated haemoglobin (HbA1c) was checked at baseline and 3 months. ResultsSixty-seven subjects were randomized to switch to CsA (n = 32) or continuation of Tac (n = 35). Both groups had similar baseline characteristics. After randomization, there was significant improvement in fasting plasma glucose, fasting insulin levels, C-peptide levels, and insulin requirement in both groups, whereas HbA1c improved significantly only in the CsA group. The decline in fasting plasma glucose and insulin requirement was more significant in subjects on CsA. An equal number of subjects in each group (59.4% in CsA group and 40% in Tac group, P = ns) had resolution of NODAT. Weight gain was more significant in the CsA group; however, there was no difference in other side effects or rejection episodes. ConclusionsA switch from tacrolimus to cyclosporine is a safe and effective strategy in patients with NODAT.

Changing Clinical Characteristics according to Insulin Resistance and Insulin Secretion in Newly Diagnosed Type 2 Diabetic Patients in Korea.

BackgroundThe role of increased insulin resistance in the pathogenesis of type 2 diabetes has been emphasized in Asian populations. Thus, we evaluated the proportion of insulin resistance and the insulin secretory capacity in patients with early phase type 2 diabetes in Korea.MethodsWe performed a cross-sectional analysis of 1,314 drug-naive patients with newly diagnosed diabetes from primary care clinics nationwide. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index to measure insulin resistance, which was defined as a HOMA-IR ≥2.5. Insulin secretory defects were classified based on fasting plasma C-peptide levels: severe (<1.1 ng/mL), moderate (1.1 to 1.7 ng/mL) and mild to non-insulin secretory defect (≥1.7 ng/mL).ResultsThe mean body mass index (BMI) was 25.2 kg/m2; 77% of patients had BMIs >23.0 kg/m2. Up to 50% of patients had central obesity based on their waist circumference (≥90 cm in men and 85 cm in women), and 70.6% had metabolic syndrome. Overall, 59.5% of subjects had insulin resistance, and 20.2% demonstrated a moderate to severe insulin secretory defect. Among those with insulin resistance, a high proportion of subjects (79.0%) had a mild or no insulin secretory defect. Only 2.6% of the men and 1.9% of the women had both insulin resistance and a moderate to severe insulin secretory defect.ConclusionIn this study, patients with early phase type 2 diabetes demonstrated increased insulin resistance, but preserved insulin secretion, with a high prevalence of obesity and metabolic syndrome.