Urinary C-peptide Research Articles

Mate-guarding constrains feeding activity but not energetic status of wild male long-tailed macaques (Macaca fascicularis)

Mate-guarding is an important determinant of male reproductive success in a number of species. Little is known however about the constraints of this behaviour, e.g. the associated energetic costs. We investigated these costs in long-tailed macaques where alpha males mate guard females to a lesser extent than predicted by the priority of access model. The study was carried out during two mating periods on three wild groups living in the Gunung Leuser National Park, Indonesia. We combined behavioural observations on males’ locomotion and feeding activity, GPS records of distance travelled and non-invasive measurements of urinary C-peptide (UCP), a physiological indicator of male energetic status. Mate-guarding led to a decrease in feeding time and fruit consumption suggesting a reduced intake of energy. At the same time, vertical locomotion was reduced, which potentially saved energy. These findings, together with the fact that we did not find an effect of mate-guarding on UCP levels, suggest that energy intake and expenditure was balanced during mate-guarding in our study males. Mate-guarding thus seems to not be energetically costly under all circumstances. Given that in strictly seasonal rhesus macaques, high-ranking males lose physical condition over the mating period, we hypothesise that the energetic costs of mate-guarding vary inter-specifically depending on the degree of seasonality and that males of non-strictly seasonal species might be better adapted to maintain balanced energetic condition year-round. Finally, our results illustrate the importance of combining behavioural assessments of both energy intake and expenditure with physiological measures when investigating energetic costs of behavioural strategies.

Urinary C-Peptide / Creatinine Ratio as a Marker for Endogenous Insulin Secretion : Relation to Microvascular Complications

Urinary C-Peptide / Creatinine Ratio as a Marker for Endogenous Insulin Secretion : Relation to Microvascular Complications

The addition of metformin and glucagon-like peptide-1 receptor agonist or dipeptidyl-peptidase-4 inhibitor to insulin for latent autoimmune diabetes in adults

Dear Sir, Latent autoimmune diabetes in adults (LADA) is considered to be a form of autoimmune diabetes that resembles type 1 diabetes though, with a later onset and slower progression toward absolute insulin requirement. There is no therapeutic strategy for LADA [1]. Here we report a patient with LADA, who showed increased intrinsic insulin secretion by the addition of metformin, and sitagliptin or exenatide to the insulin therapy. A 68-year-old woman, diagnosed to have diabetes in late 40s was treated with oral hypoglycemic agents for 17 years before insulin therapy in 2009. HbA1c levels were 6–7 % until March in 2012. Plasma glucose (520 mg/dL) and HbA1c (11.5 %) levels were high. She has been treated by using 10, 8 and 8 units of insulin glulisine before breakfast, lunch and dinner, respectively, and 18 units of insulin glargine before breakfast. Her body weight was 66.0 kg and height 152.0 cm (BMI 28.6 kg/m). The titer of anti-GAD antibody was elevated (34.0 U/ml; normal, <1.5 U/ml), and her urinary C-peptide level was reduced (4.6 μg/day; normal, 29.2–167 μg/day), suggesting LADA. Because an increase of insulin dose stimulated her appetite strongly, we started her on metformin in July, 2012, which improved her blood glucose and also increased her urinary C-peptide (22.3 μg/day) in November, 2012. The addition of sitagliptin (50 mg/day) induced more insulin secretion (52.9 μg/day), however, could not suppress her appetite completely. Therefore, we switched from sitagliptin to exenatide (10 μg/day), which remarkably suppressed her appetite and also significantly reduced daily insulin requirement (from 42 units/day to 16 units/day), and maintained intrinsic insulin secretion (51.2 μg/day). There are no studies that evaluated metformin in patients with LADA, possibly due to potential risk for the development of lactic acidosis by metformin in patients who progress toward insulin dependency [2]. We used metformin with insulin, which improved blood glucose and increased intrinsic insulin secretion without the development of lactic acidosis. To our knowledge, our report is the first to show that the addition of GLP-1 receptor agonist and dipeptidyl-peptidase4 (DPP-4) inhibitor to insulin increased intrinsic insulin secretion in a patient with LADA. In summary, the addition of metformin and GLP-1 receptor agonist or DPP-4 inhibitor to insulin may be a promising therapeutic option for LADA.

The association between postprandial urinary C‐peptide creatinine ratio and the treatment response to liraglutide: a multi‐centre observational study

The response to glucagon-like peptide1 receptor agonist treatment may be influenced by endogenous β-cell function. We investigated whether urinary C-peptide creatinine ratio assessed before or during liraglutide treatment was associated with treatment response. A single, outpatient urine sample for urinary C-peptide creatinine ratio was collected 2h after the largest meal of the day among two separate groups: (1) subjects initiating liraglutide (0.6→1.2mg daily) or (2) subjects already treated with liraglutide for 20-32weeks. The associations between pretreatment and on-treatment urinary C-peptide creatinine ratio and HbA1c change at 32weeks were assessed using univariate and multivariate analyses (the ratio was logarithm transformed for multivariate analyses). Changes in HbA1c according to pretreatment urinary C-peptide creatinine ratio quartiles are shown. One hundred and sixteen subjects (70 pretreatment, 46 on treatment) with Type2 diabetes from 10 diabetes centres were studied. In univariate analyses, neither pretreatment nor on-treatment urinary C-peptide creatinine ratio correlated with HbA1c change (Spearman rank correlation coefficient, r=-0.17, P=0.17 and r=-0.20, P=0.19, respectively). In multi-linear regression analyses, entering baseline HbA1c and log urinary C-peptide creatinine ratio, pretreatment and on-treatment log urinary C-peptide creatinine ratio became significantly associated with HbA1c change (P=0.048 and P=0.040, respectively). Mean (sd) HbA1c changes from baseline in quartiles1 to 4 of pretreatment urinary C-peptide creatinine ratio were -3±17mmol/mol (-0.3±1.6%) (P=0.52), -12±15mmol/mol (-1.1±1.4%) (P=0.003), -11±13mmol/mol (-1.0±1.2%) (P=0.002) and -12±17mmol/mol (-1.1±1.6%) (P=0.016), respectively. Postprandial urinary C-peptide creatinine ratios before and during liraglutide treatment were weakly associated with the glycaemic response to treatment. Low pretreatment urinary C-peptide creatinine ratio may be more useful than higher values by predicting poorer glycaemic response.

Urine C-peptide creatinine ratio can be used to assess insulin resistance and insulin production in people without diabetes: an observational study

ObjectivesThe current assessment of insulin resistance (IR) in epidemiology studies relies on the blood measurement of C-peptide or insulin. A urine C-peptide creatinine ratio (UCPCR) can be posted from home...

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.

The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells.

Aims/hypothesisClassically, type 1 diabetes is thought to proceed to absolute insulin deficiency. Recently developed ultrasensitive assays capable of detecting C-peptide under 5 pmol/l now allow very low levels of C-peptide to be detected in patients with long-standing type 1 diabetes. It is not known whether this low-level endogenous insulin secretion responds to physiological stimuli. We aimed to assess how commonly low-level detectable C-peptide occurs in long-duration type 1 diabetes and whether it responds to a meal stimulus.MethodsWe performed a mixed-meal tolerance test in 74 volunteers with long-duration (>5 years) type 1 diabetes, i.e. with age at diagnosis 16 (9–23) years (median [interquartile range]) and diabetes duration of 30 (19–41) years. We assessed fasting and stimulated serum C-peptide levels using an electrochemiluminescence assay (detection limit 3.3 pmol/l), and also the urinary C-peptide:creatinine ratio (UCPCR).ResultsPost-stimulation serum C-peptide was detectable at very low levels (>3.3 pmol/l) in 54 of 74 (73%) patients. In all patients with detectable serum C-peptide, C-peptide either increased (n = 43, 80%) or stayed the same (n = 11) in response to a meal, with no indication of levels falling (p < 0.0001). With increasing disease duration, absolute C-peptide levels fell although the numbers with detectable C-peptide remained high (68%, i.e. 25 of 37 patients with >30 years duration). Similar results were obtained for UCPCR.Conclusions/interpretationMost patients with long-duration type 1 diabetes continue to secrete very low levels of endogenous insulin, which increase after meals. This is consistent with the presence of a small number of still functional beta cells and implies that beta cells are either escaping immune attack or undergoing regeneration.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-013-3067-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Mizoribine-induced severe hyperglycemia in a patient with microscopic polyangiitis.

A 77-year-old woman had been receiving prednisolone (PSL) for 5months as induction therapy for microscopic polyangiitis. Because of repeated elevation of the antineutrophil cytoplasmic autoantibody titer, we added mizoribine (MZR), and, 2months later, the patient developed severe hyperglycemia with low serum and urinary C-peptide reactivity (CPR). The MZR was, therefore, withdrawn and insulin therapy was started. One month later, the serum and urinary CPR had increased and postprandial hyperglycemia had improved. Previous in vitro studies have shown that MZR can induce hyperglycemia through at least two mechanisms. One is the alteration of insulin secretion from islet cells, and the other is action via the glucocorticoid receptor (GR). MZR reduces insulin secretion through the depletion of intracellular guanosine triphosphate (GTP), which leads to the inhibition of mitogenesis and induction of beta cell apoptosis. MZR affects insulin resistance by activating the GR through interaction with the 14-3-3 protein, leading to postprandial hyperglycemia. Although postprandial hyperglycemia generally appears between 3 and 7weeks after PSL administration, that in our patient did not become apparent during 5months of PSL monotherapy, but was manifested 2months after the introduction of MZR, and improved after MZR had been withdrawn. We conclude from these findings that MZR had been responsible for the hyperglycemia in our patient.

Ecology of reproduction in Sanje mangabeys (Cercocebus sanjei): Dietary strategies and energetic condition during a high fruit period

The ability to increase energy storage when food is abundant for later use during late gestation and early lactation is often considered the primary benefit of the capital breeding strategy (clustering conceptions during high food periods, HFP) that promotes reproductive success among females living in unpredictable environments. Capital breeding, however, may also enable preconceptive females to increase hormone production for ovulation, which has been linked to energetic condition in capital breeders, and/or allow females entering the subsequent HFP to increase their energetic condition in order to continue nursing unweaned infants. Here, we investigate whether capital breeding provides these additional benefits in 16 female Sanje mangabeys (Cercocebus sanjei) and determine the dietary strategies used to increase energetic condition (measured by urinary C-peptide: UCP) during the HFP. Fecal estradiol (fE2 ) and UCP were negatively correlated with number of cycles before conception (r = -0.591, r = -0.646, P < 0.01) and were highest in conceptive cycles. Both peri-conceptive (preconception and early gestation) and non-peri-conceptive (lactation) females increased energetic condition over the HFP (r = 0.612, r = 0.583, P < 0.001) by increasing dietary fat (r = 0.619, r = 0.703, P < 0.001) and, for non-peri-conceptive females, protein (r = 0.437, P < 0.001). Feeding intake rate (FIR) and time spent foraging and feeding did not change over the HFP; however, non-peri-conceptive females exhibited a faster FIR compared to peri-conceptive females (t = -2.324, P < 0.05), consuming almost twice as much food per unit time. The results of this study confirm that Sanje mangabeys benefit in multiple phases of the reproductive cycle by using capital breeding, which may explain how this strategy promotes female reproductive success.

The clinical utility of C‐peptide measurement in the care of patients with diabetes

C-peptide is produced in equal amounts to insulin and is the best measure of endogenous insulin secretion in patients with diabetes. Measurement of insulin secretion using C-peptide can be helpful in clinical practice: differences in insulin secretion are fundamental to the different treatment requirements of Type 1 and Type 2 diabetes. This article reviews the use of C-peptide measurement in the clinical management of patients with diabetes, including the interpretation and choice of C-peptide test and its use to assist diabetes classification and choice of treatment. We provide recommendations for where C-peptide should be used, choice of test and interpretation of results. With the rising incidence of Type 2 diabetes in younger patients, the discovery of monogenic diabetes and development of new therapies aimed at preserving insulin secretion, the direct measurement of insulin secretion may be increasingly important. Advances in assays have made C-peptide measurement both more reliable and inexpensive. In addition, recent work has demonstrated that C-peptide is more stable in blood than previously suggested or can be reliably measured on a spot urine sample (urine C-peptide:creatinine ratio), facilitating measurement in routine clinical practice. The key current clinical role of C-peptide is to assist classification and management of insulin-treated patients. Utility is greatest after 3–5 years from diagnosis when persistence of substantial insulin secretion suggests Type 2 or monogenic diabetes. Absent C-peptide at any time confirms absolute insulin requirement and the appropriateness of Type 1 diabetes management strategies regardless of apparent aetiology.

The area of abdominal subcutaneous adipose tissue is independently correlated with C-peptide increment during glucagon load in Japanese patients with type 2 diabetes

Overall adiposity is associated with insulin resistance. Decline in insulin sensitivity induces a compensatory increase in insulin secretion from beta cells. The impact of adipose tissue distribution, i.e., visceral versus subcutaneous fat, on beta cell function remains to be elucidated. The aim of this study was to retrospectively investigate the relation between the areas of subcutaneous and visceral fat and the increment in C-peptide levels (CPR) during glucagon load (ΔCPR) in Japanese patients with type 2 diabetes. In 195 Japanese patients with type 2 diabetes, beta cell function was evaluated by ΔCPR, CPR index (100 × fasting CPR divided by fasting glucose), and 24-h urinary C-peptide excretion (U-CPR) during the 1-week hospitalization for diabetes education. Then, we investigated the relationships between markers of beta cell function and the areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) determined by abdominal computed tomography. Stepwise multiple regression analyses identified SAT, but not VAT, as an independent variable of both ΔCPR and U-CPR [standard regression coefficient (Stdβ) = 0.332, P < 0.01 for ΔCPR, and Stdβ = 0.181, P < 0.05 for U-CPR], and both SAT and VAT were identified as independent variables for CPR index (Stdβ = 0.253, P < 0.01 for SAT, and Stdβ = 0.193, P < 0.01 for VAT). Our results indicated that SAT is independently correlated with beta cell function by glucagon test in Japanese patients with type 2 diabetes.

Urinary C‐peptide creatinine ratio detects absolute insulin deficiency in Type 2 diabetes

To determine the prevalence and clinical characteristics of absolute insulin deficiency in long-standing Type 2 diabetes, using a strategy based on home urinary C-peptide creatinine ratio measurement. We assessed the urinary C-peptide creatinine ratios, from urine samples taken at home 2h after the largest meal of the day, in 191 insulin-treated subjects with Type 2 diabetes (diagnosis age ≥45years, no insulin in the first year). If the initial urinary C-peptide creatinine ratio was ≤0.2nmol/mmol (representing absolute insulin deficiency), the assessment was repeated. A standardized mixed-meal tolerance test with 90-min stimulated serum C-peptide measurement was performed in nine subjects with a urinary C-peptide creatinine ratio ≤ 0.2nmol/mmol (and in nine controls with a urinary C-peptide creatinine ratio >0.2nmol/mmol) to confirm absolute insulin deficiency. A total of 2.7% of participants had absolute insulin deficiency confirmed by a mixed-meal tolerance test. They were identified initially using urinary C-peptide creatinine ratio: 11/191 subjects (5.8%) had two consistent urinary C-peptide creatinine ratios ≤ 0.2nmol/mmol; 9 of these 11 subjects completed a mixed-meal tolerance test and had a median stimulated serum C-peptide of 0.18nmol/l. Five of these 9 had stimulated serum C-peptide <0.2nmol/l and 9/9 subjects with urinary C-peptide creatinine ratio >0.2 had endogenous insulin secretion confirmed by the mixed-meal tolerance test. Compared with subjects with a urinary C-peptide creatinine ratio >0.2nmol/mmol, those with confirmed absolute insulin deficiency had a shorter time to insulin treatment (median 2.5 vs. 6years, P=0.005) and lower BMI (25.1 vs. 29.1kg/m(2) , P=0.04). Two out of the five patients with absolute insulin deficiency were glutamic acid decarboxylase autoantibody-positive. Absolute insulin deficiency may occur in long-standing Type 2 diabetes, and cannot be reliably predicted by clinical features or autoantibodies. Absolute insulin deficiency in Type 2 diabetes may increase the risk of hypoglycaemia and ketoacidosis, as in Type 1 diabetes. Its recognition should help guide treatment, education and management. The urinary C-peptide creatinine ratio is a practical non-invasive method to aid detection of absolute insulin deficiency, with a urinary C-peptide creatinine ratio > 0.2nmol/mmol being a reliable indicator of retained endogenous insulin secretion.

Defining criteria for the introduction of liraglutide using the glucagon stimulation test in patients with type2 diabetes.

To define a set of criteria using indices of β-cell function, including results from the glucagon stimulation test, for liraglutide introduction in patients with type2 diabetes. In the present retrospective cohort study, patients were included in our analysis if their β-cell function had been evaluated with a glucagon stimulation test and a 24-h urinary C-peptide (U-CPR) excretion test before switching from insulin therapy to liraglutide monotherapy. The efficacy of liraglutide was determined by the extent to which glycemic control was achieved or if glycated hemoglobin levels were maintained at <7.0% after liraglutide monotherapy for 24weeks. Liraglutide was effective in 36 of 77 patients. In the liraglutide-effective cases, the following parameters were higher: fasting C-peptide (CPR0) levels, C-peptide levels 6min after glucagon stimulation (CPR6), the C-peptide index (CPI; CPR0×100/fasting plasma glucose) and stimulated C-peptide index (S-CPI; CPR6×100/plasma glucose 6min after glucagon stimulation). U-CPR did not differ between liraglutide-effective and liraglutide-ineffective cases. Using receiver operating characteristic analysis adjusted for baseline characteristics, the independent cut-off value for effective liraglutide introduction was 0.72 for CPI and 1.92 for S-CPI. Evaluation of β-cell function using the glucagon stimulation test is useful for determining the efficacy of liraglutide introduction in patients with type2 diabetes.

A Palaeolithic‐type diet causes strong tissue‐specific effects on ectopic fat deposition in obese postmenopausal women

Ectopic fat accumulation in liver and skeletal muscle may be an essential link between abdominal obesity, insulin resistance and increased risk of cardiovascular disease after menopause. We hypothesized that a diet containing a relatively high content of protein and unsaturated fat [mainly monounsaturated fatty acids (MUFAs)] but limited carbohydrates and saturated fat would reduce lipid content in liver and muscle and increase insulin sensitivity in postmenopausal women. Ten healthy, nonsmoking postmenopausal women with a body mass index (BMI) >27 (28-35) kg m(-2) were included in the study. Participants were instructed to consume an ad libitum Palaeolithic-type diet intended to provide approximately 30 energy percentage (E%) protein, 40 E% fat (mainly MUFAs) and 30 E% carbohydrate. Intramyocellular lipid (IMCL) levels in calf muscles and liver triglyceride levels were quantified using proton magnetic resonance spectroscopy ((1) H-MRS) before and 5 weeks after dietary intervention. Insulin sensitivity was estimated by homoeostasis model assessment (HOMA) indices and the euglycaemic hyperinsulinaemic clamp technique. Mean energy intake decreased by 25% with a weight loss of 4.5 kg. BMI, waist and hip circumference, waist/hip ratio and abdominal sagittal diameter also decreased significantly, as did diastolic blood pressure (mean -7 mmHg), levels of fasting serum glucose, cholesterol, triglycerides, LDL/HDL cholesterol, apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1), urinary C-peptide and HOMA indices. Whole-body insulin sensitivity did not change. Liver triglyceride levels decreased by 49%, whereas IMCL levels in skeletal muscle were not significantly altered. A modified Palaeolithic-type diet has strong and tissue-specific effects on ectopic lipid deposition in postmenopausal women.

Urinary C-peptide creatinine ratio to detect absolute insulin deficiency in type 2 diabetes

BackgroundNational Institute for Health and Clinical Excellence guidelines (CG87) recommend neutral protamine hagedorn (NPH) insulin for the provision of basal insulin in type 2 diabetes, but use of analogue insulin is as much as 40%. Where residual endogenous insulin secretory capacity is present there is no evidence that analogue insulins provide any additional benefit over human insulins, and they come at an expensive premium. Anecdotally, however, there is a reluctance to switch people back to NPH insulin, partly because of a perceived risk of pancreatic failure and potential ketosis. Urinary C-peptide creatinine ratio (UCPCR) has been validated as a method for evaluating residual endogenous insulin secretion in type 1 and type 2 diabetes, with a UCPCR of no more than 0·2 nmol/mmol suggestive of absolute insulin deficiency. We aimed to evaluate the prevalence of true insulin deficiency among patients with type 2 diabetes with UCPCR, and confirm findings with the gold standard mixed meal tolerance test (MMTT). Methods191 insulin-treated patients with a clinical diagnosis of type 2 diabetes (diagnosed at or after age 45 years and who did not start insulin within the first year of diagnosis) collected a 2-h post-prandial urine sample for UCPCR measurement. Nine patients from two subgroups (UCPCR ≤0·2 nmol/mmol and UCPCR >0·2) completed a standard MMTT. Findings11 (5·8%) of 191 patients had two consistent UCPCRs of less than or equal to 0·2 nmol/mmol. Nine were able to do the MMTT, of whom five were confirmed to have absolute insulin deficiency (stimulated serum c-peptide <0·2 nmol/L). Three of these five patients were glutamic acid decarboxylase antibody-negative. Nine of nine patients with UCPCR of more than 0·2 nmol/L had confirmed endogenous insulin secretion in their MMTT. Those with insulin deficiency had a shorter time to starting insulin (median 2·5 years [IQR 1·5–3·0] vs 6·0 [3·0–10·75], p=0·005) and lower body-mass index (25 kg/m2vs 29, p=0·04) but no other significant differences in clinical characteristics. InterpretationWe have demonstrated a very low prevalence of true pancreatic failure in this population of insulin-treated patients with type 2 diabetes. This requires further exploration by comparison of a population being treated with NPH insulin with one on analogue insulin, and then determining whether UCPCR could act as a clinical decision support tool to safely switch from analogue insulin to NPH insulin. FundingNational Institute for Health Research.

Reproductive seasonality in wild Sanje mangabeys (Cercocebus sanjei), Tanzania: Relationship between the capital breeding strategy and infant survival

The reproductive seasonality model states that it is adaptive for species in seasonally variable environments to temporally cluster reproductive events around periods of resource availability. Many studies have examined links between seasonal reproduction and phenological events, though few studies have fully tested the adaptive hypothesis by examining the effects of reproductive timing on outcomes. Our study tests the predictions of the model in an African cercopithecine, the Sanje mangabey, by examining the impact of food availability on the timing of conception, birth and weaning, and the relationship of reproductive timing and female energy balance (urinary C-peptide) to infant survival. From September 2008 through 2010, 28 infants were born. Distribution of conceptions was non-uniform, with a peak between January and March. There was a significant positive correlation between mean monthly fruit availability and number of conceptions per month. An increased food supply supports a positive energy balance, maximizing the potential for conception; a pattern found among many cercopithecines. Mothers that conceived within the peak period also exhibited higher levels of urinary C-peptide during preconception and early gestation, compared to conceptions outside the peak period. This strategy increased the probability of survival to year one, as it was significantly higher for infants conceived during the peak conceptive season. These results support the reproductive seasonality model and demonstrate that the timing of conception is critical for mangabey reproductive success.

Home urine C-peptide creatinine ratio testing can identify type 2 and MODY in pediatric diabetes

Making the correct diabetes diagnosis in children is crucial for lifelong management. Type 2 diabetes and maturity onset diabetes of the young (MODY) are seen in the pediatric setting, and can be difficult to discriminate from type 1 diabetes. Postprandial urinary C-peptide creatinine ratio (UCPCR) is a non-invasive measure of endogenous insulin secretion that has not been tested as a diagnostic tool in children or in patients with diabetes duration <5 yr. We aimed to assess whether UCPCR can discriminate type 1 diabetes from MODY and type 2 in pediatric diabetes. Two-hour postprandial UCPCR was measured in 264 patients aged <21 yr (type 1, n = 160; type 2, n = 41; and MODY, n = 63). Receiver operating characteristic curves were used to identify the optimal UCPCR cutoff for discriminating diabetes subtypes. UCPCR was lower in type 1 diabetes [0.05 (<0.03-0.39) nmol/mmol median (interquartile range)] than in type 2 diabetes [4.01 (2.84-5.74) nmol/mmol, p < 0.0001] and MODY [3.51 (2.37-5.32) nmol/mmol, p < 0.0001]. UCPCR was similar in type 2 diabetes and MODY (p = 0.25), so patients were combined for subsequent analyses. After 2-yr duration, UCPCR ≥ 0.7 nmol/mmol has 100% sensitivity [95% confidence interval (CI): 92-100] and 97% specificity (95% CI: 91-99) for identifying non-type 1 (MODY + type 2 diabetes) from type 1 diabetes [area under the curve (AUC) 0.997]. UCPCR was poor at discriminating MODY from type 2 diabetes (AUC 0.57). UCPCR testing can be used in diabetes duration greater than 2 yr to identify pediatric patients with non-type 1 diabetes. UCPCR testing is a practical non-invasive method for use in the pediatric outpatient setting.

Nilotinib exacerbates diabetes mellitus by decreasing secretion of endogenous insulin

We report a 74-year-old female with chronic myelogenous leukemia (CML) in accelerated phase with pre-existing severe type 2 diabetes (T2D) and hemorrhagic gastric ulcers who was successfully treated with nilotinib. We first considered second-generation tyrosine kinase inhibitors for the treatment of this patient, as they elicit a superior response compared with imatinib. We next selected nilotinib, rather than dasatinib, since the increased risk of bleeding associated with dasatinib represented a greater risk of fatality than aggravation of T2D with nilotinib. After improvement of hemorrhagic gastric ulcers and T2D with exogenous insulin therapy, we began nilotinib administration; insulin dose was increased to maintain her glucose levels whereas urine C-peptide level decreased. Conversely, when nilotinib was discontinued due to liver dysfunction, the dosage of injected insulin was decreased and urine C-peptide levels increased. After re-starting nilotinib, the required dose of insulin gradually increased again, and urine C-peptide level decreased, indicating that nilotinib may have impaired secretion of endogenous insulin. The patient obtained a complete cytogenetic response after 3months of nilotinib treatment. Her T2D has since been well controlled by insulin therapy. To our knowledge, this is the first report that nilotinib treatment for patients with severe T2D may induce a reversible decrease in endogenous insulin secretion, although the precise underlying mechanisms remain unknown. We highly recommend sufficient screening and early intervention with exogenous insulin therapy for diabetic CML patients who receive nilotinib.

Analysis of clinical factors contributing to the postglucagon increment in C-peptide levels in Japanese patients with type 2 diabetes: comparison with basal C-peptide levels and 24-h urinary C-peptide excretion

We investigated the clinical factors that affected routine laboratory tests of C-peptide levels (CPR) used for the evaluation of β-cell function in Japanese patients with type 2 diabetes. The study subjects were 215 Japanese patients with type 2 diabetes admitted to Juntendo University Hospital just for glycemic control. β-cell function was evaluated by ΔCPR (6-min postglucagon increment in CPR), CPR index (100 × fasting CPR divided by fasting glucose), and 24-h urinary CPR excretion (U-CPR). Stepwise multiple regression analyses of relationships between clinical parameters and these laboratory tests were carried out. The analysis identified BMI and treatment with insulin before admission, but not glycosylated hemoglobin at admission, as independent determinants of all β-cell function tests [BMI: Stdβ (standard regression coefficient) = 0.337, P < 0.01 for ΔCPR, Stdβ = 0.365, P < 0.01 for CPR index, and Stdβ = 0.207, P < 0.01 for U-CPR, and treatment with insulin before admission: Stdβ = −0.141, P = 0.023 for ΔCPR, Stdβ = −0.285, P < 0.01 for CPR index, and Stdβ = −0.258, P < 0.01 for U-CPR]. The estimated glomerular filtration rate (eGFR) was an independent determinant of U-CPR (Stdβ = 0.145, P = 0.023), but not ΔCPR. In conclusion, ΔCPR evaluates β-cell function without being affected by eGFR and glycemic control over the preceding 2–3 months.

Postprandial serum C-peptide is a useful parameter in the prediction of successful switching to liraglutide monotherapy from complex insulin therapy in Japanese patients with type 2 diabetes

AimsLiraglutide improves glycemic control in patients with type 2 diabetes. However, no information is available about an indicator of successful switching to liraglutide monotherapy from complex insulin therapy in Japanese patients with type 2 diabetes. MethodsWe studied 69 patients with type 2 diabetes, including 39 consecutive successful patients and 30 consecutive unsuccessful patients from insulin therapy to liraglutide monotherapy. Before switching, we measured urinary C-peptide, fasting C-peptide and postprandial C-peptide at 30, 60 and 120 min loading a test meal. In successful patients, HbA1c and body weight were measured at 4, 8, and 12weeks after switching. ResultsUsing univariate analysis, duration of disease was significantly higher in unsuccessful patients than in successful patients. Urinary C-peptide, fasting C-peptide, and postprandial C-peptides were significantly higher in successful patients than in unsuccessful patients. Multiple logistic regression analysis showed that postprandial C-peptide at 60 min was an independent predictor of successful switching to liraglutide monotherapy from insulin therapy (odds ratio, 7.28; 95% confidence interval, 2.89–18.36). In the receiver operating characteristic analyses, 2.9ng/mL of postprandial C-peptide at 60 min was the best cut-off value, providing that sensitivity and specificity were 95% and 93%, respectively. In the follow-up period, successful patients showed a sustained reduction in HbA1c and body weight without hypoglycemia. ConclusionsPostprandial C-peptide at 60 min is a useful parameter in the prediction of successful switching from insulin therapy to liraglutide monotherapy in Japanese patients with type 2 diabetes.