Urinary C-peptide Excretion Research Articles

Impact of time-restricted feeding on kidney injury in male rats with experimental metabolic syndrome.

Disruptions to circadian rhythm may be implicated in the pathogenesis of metabolic syndrome (Met-S). For example, eating during an extended period of the day may negatively impact the circadian rhythms governing metabolic control, contributing, therefore, to Met-S and associated end-organ damage. Accordingly, time-restricted eating (TRE)/feeding (TRF) is gaining popularity as a dietary intervention for the treatment and prevention of Met-S. To date, no studies have specifically examined the impact of TRE/TRF on the renal consequences of Met-S. The proposed study seeks to use a model of experimental Met-S-associated kidney disease to address this knowledge gap, disambiguating therein the effects of calorie restriction from the timing of food intake. Spontaneously hypertensive ratswill consume a high-fat diet (HFD) for 8weeks and then be allocated by stratified randomisation according to albuminuria to one of three groups.Rats will have free 24-h access to HFD (Group A), access to HFD during the scheduled hours of darkness (Group B) or access to HFD provided in the form of two rations, one provided during the light phase and one provided during the dark phase, equivalent overall in quantity to that consumed by rats in Group B (Group C). The primary outcome measure will be a change inalbuminuria. Changes in food intake, body weight, blood pressure, glucose tolerance, fasting plasma insulin, urinary excretion of C-peptide and renal injury biomarkers, liver and kidney histopathology and inflammation, and fibrosis-related renal gene expression will be assessed as secondary outcomes.

PS-C29-7: ASSOCIATION OF SERUM LEPTIN TO ADIPONECTIN RATIO AND CARDIOVASCULAR STRUCTURAL INDICES IN ESSENTIAL HYPERTENSIVE PATIENTS WITHOUT CHRONIC KIDNEY DISEASE

Objective: Dysregulated leptin and adiponectin profile is known to be associated with atherosclerotic disease. The evaluation of the leptin to adiponectin (L/A) ratio has been suggested as a powerful useful atherosclerotic index compared with adiponectin and leptin alone in patients with type 2 diabetes and obesity. In this study, we investigated the usefulness of L/A ratio for vascular structural abnormalities in essential hypertensive patients. Design and method: In 151 untreated essential hypertensive patients (86 males, average age 56 ± 12 years) without chronic kidney disease (urinary albumin excretion (UAE) less than 300 mg/g of creatinine and estimated glomerular filtration rate 60 mL/min/1.73m2 or more), blood sampling, 24-hour urine collection, and 24-hour blood pressure monitoring were performed. Intima-media thickness of carotid artery (IMT) and minimal forearm vascular resistance (MVR) (wall to lumen ratio in resistance vessel) were also measured by using ultrasonography and strain-gauge plethysmography, respectively. Results: L/A ratio was higher in men than in women (1.23 ± 1.56 vs 0.73 ± 0.87, p < 0.05). There was no correlation between L/A ratio and systolic and diastolic blood pressure, and pulse rate. L/A ratio correlated positively with body mass index, triglyceride, hemoglobin A1c, HOMA-R and urinary C-peptide excretion (r = 0.57, 0.20, 0.20, 0.31, 0.27, p < 0.05, respectively) and negatively with HDL-cholesterol (r = -0.24, p < 0.05). In addition, UAE, IMT and MVR were increased accompanying incremental L/A ratio (r = 0.20, 0.17, 0.19, p < 0.05, respectively)In addition, UAE, IMT and MVR were increased accompanying incremental L/A ratio (r = 0.20, 0.17, 0.19, p < 0.05, respectively), whereas these indices did not associated with leptin and adiponectin individually. In multiple regression analysis, L/A ratio was an independent determinant for UAE, IMT and MVR. Conclusions: In patients with essential hypertension, L/A ratio was associated with obesity, abnormal glucose and lipid metabolism, increase in microalbuminuria, and arterial and arteriolar sclerosis. L/A ratio was considered as a useful indicator of vascular structural abnormalities in patients with essential hypertension.

Deciphering genetic signatures by whole exome sequencing in a case of co-prevalence of severe renal hypouricemia and diabetes with impaired insulin secretion

BackgroundRenal hypouricemia (RHUC) is a hereditary disorder where mutations in SLC22A12 gene and SLC2A9 gene cause RHUC type 1 (RHUC1) and RHUC type 2 (RHUC2), respectively. These genes regulate renal tubular reabsorption of urates while there exist other genes counterbalancing the net excretion of urates including ABCG2 and SLC17A1. Urate metabolism is tightly interconnected with glucose metabolism, and SLC2A9 gene may be involved in insulin secretion from pancreatic β-cells. On the other hand, a myriad of genes are responsible for the impaired insulin secretion independently of urate metabolism.Case presentationWe describe a 67 year-old Japanese man who manifested severe hypouricemia (0.7 mg/dl (3.8–7.0 mg/dl), 41.6 μmol/l (226–416 μmol/l)) and diabetes with impaired insulin secretion. His high urinary fractional excretion of urate (65.5%) and low urinary C-peptide excretion (25.7 μg/day) were compatible with the diagnosis of RHUC and impaired insulin secretion, respectively. Considering the fact that metabolic pathways regulating urates and glucose are closely interconnected, we attempted to delineate the genetic basis of the hypouricemia and the insulin secretion defect observed in this patient using whole exome sequencing. Intriguingly, we found homozygous Trp258* mutations in SLC22A12 gene causing RHUC1 while concurrent mutations reported to be associated with hyperuricemia were also discovered including ABCG2 (Gln141Lys) and SLC17A1 (Thr269Ile). SLC2A9, that also facilitates glucose transport, has been implicated to enhance insulin secretion, however, the non-synonymous mutations found in SLC2A9 gene of this patient were not dysfunctional variants. Therefore, we embarked on a search for causal mutations for his impaired insulin secretion, resulting in identification of multiple mutations in HNF1A gene (MODY3) as well as other genes that play roles in pancreatic β-cells. Among them, the Leu80fs in the homeobox gene NKX6.1 was an unreported mutation.ConclusionWe found a case of RHUC1 carrying mutations in SLC22A12 gene accompanied with compensatory mutations associated with hyperuricemia, representing the first report showing coexistence of the mutations with opposed potential to regulate urate concentrations. On the other hand, independent gene mutations may be responsible for his impaired insulin secretion, which contains novel mutations in key genes in the pancreatic β-cell functions that deserve further scrutiny.

Intractable Coronary Artery Disease in a Patient With Type 2 Diabetes Presenting With Triglyceride Deposit Cardiomyovasculopathy.

The patient was a 51-year-old man who had been overweight since adolescence and was diagnosed with type 2 diabetes at age 26. He had been treated with a sulfonylurea, but his glycemic control was poor. When his medication was replaced with insulin injection at age 35, KITT, a marker of insulin sensitivity (1), was severely deteriorated to 0.87%, and resulting endogenous hyperinsulinemia was suspected from total daily urinary C-peptide excretion (242.8 μg). At that time, he was overweight by BMI (27.1 kg/m2). Lipid profiles showed mild hypertriglyceridemia with apolipoprotein E3/3 phenotype. His …

Comparison of Disparities between FGM/CGM Sensor Glucose Values and Blood Glucose Values in Type 1 Diabetic Patients on SAP Therapy

Objective: Disparities were compared between flash glucose monitoring (FGM) sensor glucose (SG) and blood glucose (BG) values vs. between continuous glucose monitoring (CGM) SG and BG values to establish the accuracy of FGM SG values in patients with type 1 diabetes. Methods: FGM (FreeStyle Libre Pro; Abbott Japan) and a sensor-augmented pump (SAP) with built-in CGM (MiniMed 620G; Medtronic Minimed) were simultaneously put in place in 8 outpatients with type 1 diabetes receiving SAP therapy (Age, 50.9 ± 6.3 years; BMI, 20.4±2.6 kg/m2; HbA1c, 7.4±0.3%; urinary C-peptide excretion, 1.5±0.7 µg/day; duration of SAP therapy, 11.9±3.7 months; insulin dose, 34.2±14.5 U/day). SMBG BG values at 385 points registered on Minimed 620G for calibration purposes and CGM/FGM SG values at the same time points, were selected to examine the accuracy of FGM SG values. Both these devices were evaluated for accuracy in terms of 1) simple correlation coefficients between CGM/FGM SG values and BG values; and 2) mean absolute relative differences (MARD) in SG values of CGM/FGM relative to BG values as reference. Results: 1) A strong positive correlations were found between the CGM/FGM SG values and BG values (r = 0.984, p < 0.001 / r = 0.852, p< 0.001). 2) The MARD in CGM/FGM SG values were 5.81 ± 6.66% (0-39.4%) / 17.5 ± 24.8% (0-213.6%), and the frequency of MARD showing 10% or less accounted for 83% of all CGM SG values, and 48.3% of all FGM SG values. The relationship between the MARD of FGM SG values and the durations of FGM put in place varied depending on the number of days FGM put in place. Additionally, the disparity between the FGM SG values and the BG values varied greatly depending on the individual patient. Conclusions: While FGM represents an innovative device for glucose monitoring, there is a wide disparity between the FGM SG and BG values in some patients with type 1 diabetes, suggesting that FGM may be appropriately positioned as an adjunct, but not an alternative, to SMBG. Disclosure M. Tanizawa: None. H. Takahashi: None. Y. Mori: None. K. Utsunomiya: None.

Urinary C-Peptide Excretion for Diabetic Treatment in Low Carbohydrate Diet (LCD)

Background: Arguments have continued about Low Carbohydrate Diet (LCD) and Calorie Restriction (CR). Authors have reported clinical research of LCD and Morbus (M) value. Subjects and Methods: Subjects enrolled are 84 patients with Type 2 diabetes mellitus (T2DM), 60.9 ± 10.9 years. The protocol were as follows: 1) CR diet on day 1, 2 with 60% carbohydrates, and LCD on day 3-14 with 12% carbohydrates, 2) Daily profile of blood glucose 7 times a day on day 2 (CR) and day 4 (LCD), 3) urinary C-Peptide radioimmunoassay (u-CPR) excretion, 4) M value calculation, 5) investigation of these data with correlation. Results: Subjects were classified into 4 groups according to M value, which were .4–21, 23–66, 29–192, 200–728, respectively. HbA1c value was 6.2, 8.0, 7.8, 9.2 %, respectively. Blood glucose in median from day 2 to day 4 were 123 to 107 mg/dL, 164 to 130 mg/dL, 193 to 156 mg/dL, 277 to 201 mg/dL, respectively. M value in median from day 2 to 4 was 6.3 to 9, 41 to 7, 108 to 16, 367 to 88, respectively. u-CPR was 88 to 58, 53 to 35, 65 to 52, 74 to 64, respectively. There were significant correlations among among glucose, M value and u-CPR. Discussion and Conclusion: Average glucose, M value and u-CPR decreased remarkably on day 4. As average glucose and M value were higher, decrease degree were larger. These results suggested that carbohydrate in meal would influence glucose variability in T2DM. Our data would become basic data for pathophysiological analysis of glucose variability research in the future.

C-Peptide Clearance: Potential Marker of Endogenous Insulin Secretion for Pkpd Studies of Insulin In Neonates

Insulin and C-peptide are secreted in equimolar amounts from the pancreas [1]. However, since C-peptide is not hepatically cleared, it may be possible to estimate insulin secretion from the urinary C-peptide excretion rate [1]. This may give a noninvasive way of measuring insulin production in neonates [2].

Relationship between whole-body macronutrient oxidative partitioning and pancreatic insulin secretion/β-cell function in non-diabetic humans

BackgroundGlucose-stimulated insulin secretion correlates inversely with the degree of whole-body insulin sensitivity suggesting a crosstalk between peripheral organs and pancreas. Such sensing mechanism could be mediated by changes in glucose flux (uptake, oxidation or storage) in peripheral tissues that may drive insulin secretion. AimTo relate whole-body non-protein respiratory quotient (npRQ), an index of macronutrient oxidative partitioning, with insulin secretion and β-cell function in non-diabetic individuals. MethodsMacronutrient oxidation was measured after an overnight fast and for 4h after a 75-g oral glucose tolerance test (OGTT) in 30 participants (15/15 males/females; 35±12y; 27±4kg/m2). Furthermore, npRQ was assessed for 24h in a metabolic chamber. Insulin secretion was estimated by deconvolution of serum C-peptide concentration (fasting and 4-h OGTT) and from 24-h urinary C-peptide excretion corrected for energy intake (metabolic chamber). β-Cell function parameters were obtained by mathematical modeling, while insulin sensitivity was determined by a euglycemic–hyperinsulinemic clamp (120mU·m−2·min−1). ResultsInsulin secretion (from 24-h urinary C-peptide) correlated inversely with 24-h npRQ (r=−0.61; p=0.001), even after controlling for insulin sensitivity, energy balance, age and body mass index (r=−0.52; p=0.01). In turn, insulin secretion (from serum C-peptide) was not associated with fasting or OGTT npRQ. However, fasting npRQ was positively correlated with rate sensitivity (r=0.40; p<0.05) and marginally with glucose sensitivity (r=0.34; p=0.08). ConclusionMacronutrient oxidative partitioning, specifically glucose oxidation, might play a role on the regulation of insulin secretion. Further studies should aim at identifying the signals linking these processes.

Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on C-peptide kinetics.

Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves indices of β-cell function estimated based on circulating C-peptide and glucose concentrations (e.g., Homeostasis Model Assessment [HOMA2-%B], meal tolerance test-based indices). However, use of these β-cell function indices assumes C-peptide kinetics are not altered by canagliflozin. This 2-period crossover study assessed the effect of a single canagliflozin 300-mg dose on C-peptide kinetics in 10 healthy participants. Two hours after receiving canagliflozin or placebo, participants received intravenous somatostatin infusion to suppress endogenous C-peptide secretion and 1 hour later received a bolus injection of synthetic human C-peptide 150 µg. Serum C-peptide was measured over 3 hours and urinary glucose and C-peptide excretion were measured. C-peptide kinetic parameters, including total clearance (CLtotal ) and renal clearance (CLrenal ), were calculated. Serum C-peptide profiles were similar following canagliflozin or placebo treatment. C-peptide CLtotal was slightly lower with canagliflozin versus placebo (mean (SD) of 190 (37) vs. 197 (30) mL/min; canagliflozin/placebo ratio [90% CI] = 96.1% [93.0%; 99.3%]). Other kinetic parameters, including CLrenal , were generally similar between treatments. Results indicate canagliflozin 300 mg does not meaningfully alter C-peptide clearance or other kinetic parameters; therefore, C-peptide-based measurements of insulin secretion are appropriate for assessing β-cell function in canagliflozin-treated participants.

Hyperinsulinemia leads the elevation of plasma aldosterone concentration independently with obesity, dyslipidemia, and insulin resistance in patients with type 2 diabetes mellitus

1) Abstract The study was to define plasma insulin level with the association of renin‑angiotensin‑aldosterone system activity in patients with type 2 diabetes. One hundred fi fty type 2 diabetic patients and 24 non‑diabetic subjects were studied. There was no statistical diff erence between the two groups in age gender the prevalence of hypertension and serum potassium concentration. Plasma aldosterone concentration (PAC) was signifi cantly higher in type 2 diabetics than that in non‑diabetic subjects (10.4±4.9 vs. 7.4±3.7 ng/dl;p=0.004) ; however plasma renin activity (PRA) did not diff er signifi cantly between the two groups. In diabetic patients PAC correlated signifi cantly with body mass index (BMI) fasting plasma insulin (F‑IRI) homeostasis model assessment insulin resistance (HOMA‑R) urinary C‑peptide excretion (U‑CPR) triglyceride (TG) and high‑density lipoprotein cholesterol (HDL‑C) . PRA correlated signifi cantly with F‑IRI and HOMA‑R but did not correlate with BMI U‑CPR TG and HDL‑C. The additional contribution of U‑CPR in predicting PAC was signifi cant after adjustment for age BMI F‑IRI TG HDL‑C and PRA (β=0.204 p=0.016) . These fi ndings indicate that hyperinsulinemia may aff ect the increase in PAC unrelated with obesity dyslipidemia insulin resistance that are components of metabolic syndrome in patients with type 2 diabetes.

Olanzapine-induced severe hyperglycemia was completely reversed by the restoration of insulin secretion after switching to aripiprazole and initiating insulin therapy

A 54-year-old Japanese man who had received a diagnosis of schizophrenia and been treated with olanzapine for nearly 16 months consulted our department because of severe hyperglycemia (535 mg/dL). The use of antipsychotics, switching the patient from olanzapine to aripiprazole, and 7 weeks of insulin therapy resulted in a decrease in the patient's postprandial blood glucose levels and an increase in his postprandial C-peptide levels (442 mg/dL to 106 mg/dL and 1.72 ng/mL to 4.94 ng/mL, respectively) as well as an improvement in his pre-prandial levels (250 mg/dL to 85 mg/dL and 1.00 ng/mL to 1.69 ng/mL, respectively) with almost no change in the 24- hour urinary excretion of C-peptide. These results suggested that an insufficiency of insulin secretion, not insulin resistance, was associated with the patient's severe hyperglycemia, and that olanzapine-induced pancreatic β-cell impairment might be reversible if the hyperglycemia is diagnosed and treated sufficiently early. When prescribing second-generation antipsychotics such as olanzapine, clinicians should take the level of insulin into account in addition to monitoring serum glucose levels.

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.

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.

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.

Slowly Progressive Insulin-Dependent Diabetes in a Patient with Primary Biliary Cirrhosis with Portal Hypertension-Type Progression

A 73-year-old woman had previously been diagnosed with CREST syndrome, PBC and diabetes. Hepatic fibrosis was not evident, in spite of the transudative ascites and active esophageal varices. ACA were positive, whereas AMA and anti-gp210 antibodies were negative. She showed low urinary excretion of C-peptide and was weakly positive for anti-GAD antibody. She was diagnosed with a form of PBC that progresses via portal hypertension rather than liver failure and with SPIDDM. Her HLA type did not contain risk allele for IDDM or PBC. SPIDDM should be considered when patients with PBC with portal hypertension-type progression develop diabetes.

Assessment of dietary exposure related to dietary GI and fibre intake in a nutritional metabolomic study of human urine

There is a need for a tool to assess dietary intake related to the habitual dietary glycaemic index (GI) and fibre in groups with large numbers of individuals. Novel metabolite-profiling techniques may be a useful approach when applied to human urine. In a long-term, controlled dietary intervention study, metabolomics were applied to assess dietary patterns. A targeted approach was used to evaluate the effects on urinary C-peptide excretion caused by the dietary treatments. Seventy-seven overweight subjects followed an 8-week low-calorie diet (LCD) and were then randomly assigned to a high-GI or low-GI diet for 6month during which they completed 24-h urine collections at baseline (prior to the 8-week LCD) and after randomisation to the dietary intervention, at month 1, 3 and 6, respectively. Metabolite profiling in 24-h urine was performed by (1)H NMR and chemometrics. Partial least squares (PLS) analysis indicated that urinary formate could discriminate between high-GI and low-GI diets (correlation coefficient r=0.82), and this finding was confirmed statistically (P=0.01). PLS analysis also indicated that urinary hippurate could be associated with fibre intake, but this finding was not confirmed statistically. No associations between GI and urinary C-peptide were found. Our results emphasise that application of metabolomics is useful in the assessment of dietary exposure related to dietary GI and fibre seen at group level in a nutritional metabolomic study of human urine. As our design allowed for large variations in individually selected food items, biomarkers identified at group level may be interpreted as more general and robust markers, largely not confounded with markers from single dietary factors.

糖尿病患者におけるC-peptide Clearance/Creatinine Clearanceの評価およびその比による24時間尿中C-peptideの補正の試み

糖尿病患者におけるC-peptide Clearance/Creatinine Clearanceの評価およびその比による24時間尿中C-peptideの補正の試み

Agenesis of the dorsal pancreas: a rare cause of diabetes

A 19-year-old Japanese man visited our department presenting with glycosuria that had been detected during a routine school urinalysis. The patient had undergone cardiac surgery at the age of 4 years for atrial and ventricular septal defects, and pulmonary artery stenosis. He denied any history of abdominal trauma, drug or alcohol intake, or gastrointestinal problems. His maternal grandmother had mild diabetes that began in middle age; whereas, his parents had no significant medical history including diabetes. The physical examination revealed an emaciated young man with a body mass index of 19.3, but otherwise a normal examination. Laboratory studies were: fasting hyperglycaemia of 19.7 mmol/l (354 mg/dl) without ketosis. The HbA1c was 12.1%, urinary excretion of C-peptide 43.9 lg/day (normal range 50–100 lg/day). The anti-islet cell and anti-glutamic acid decarboxylase antibodies were negative. The serum total amylase level was normal, 49 U/l (normal range 40–180 U/l); whereas, the levels of serum pancreatic enzymes p-type amylase, lipase, trypsin and phospholipase A2 were decreased to 8 U/l (normal range 17–50 U/l), 10 U/l (13–49 U/l), 50 U/l (100–550 U/l) and 100 U/l (130–400 U/l), respectively. Ultrasonography (US) of the abdomen could not identify the body of the pancreas, although the head and uncus were clearly visible. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed that most of the body and the tail of the pancreas were absent, and that the pancreatic head was slightly enlarged (Fig. 1). Magnetic resonance cholangiopancreatography (MRCP) revealed that the dorsal pancreatic duct was absent. Based on these findings, a diagnosis of agenesis of the dorsal pancreas was made. Insulin replacement therapy was initiated, and currently, the diabetes is well controlled with 4 U of insulin per day. There are no signs of any diabetes-related renal, retinal or neurological changes. His blood glucose levels have improved after beginning insulin therapy, and he is being followed up as a hospital outpatient.

Rye Whole Grain and Bran Intake Compared with Refined Wheat Decreases Urinary C-Peptide, Plasma Insulin, and Prostate Specific Antigen in Men with Prostate Cancer1–3

Rye whole grain and bran intake has shown beneficial effects on prostate cancer progression in animal models, including lower tumor take rates, smaller tumor volumes, and reduced prostate specific antigen (PSA) concentrations. A human pilot study showed increased apoptosis after consumption of rye bran bread. In this study, we investigated the effect of high intake of rye whole grain and bran on prostate cancer progression as assessed by PSA concentration in men diagnosed with prostate cancer. Seventeen participants were provided with 485 g rye whole grain and bran products (RP) or refined wheat products with added cellulose (WP), corresponding to ~50% of daily energy intake, in a randomized controlled, crossover design. Blood samples were taken from fasting men before and after 2, 4, and 6 wk of treatment and 24-h urine samples were collected before the first intervention period and after treatment. Plasma total PSA concentrations were lower after treatment with RP compared with WP, with a mean treatment effect of −14% (P = 0.04). Additionally, fasting plasma insulin and 24-h urinary C-peptide excretion were lower after treatment with RP compared with WP (P < 0.01 and P = 0.01, respectively). Daily excretion of 5 lignans was higher after the RP treatment than after the WP treatment (P < 0.001). We conclude that whole grain and bran from rye resulted in significantly lower plasma PSA compared with a cellulose-supplemented refined wheat diet in patients with prostate cancer. The effect may be related to inhibition of prostate cancer progression caused by decreased exposure to insulin, as indicated by plasma insulin and urinary C-peptide excretion.

Urinary C‐Peptide Excretion: A Novel Alternate Measure of Insulin Sensitivity in Physiological Conditions

Insulin sensitivity (IS) is measured by the euglycemic-hyperinsulinemic clamp under a nonphysiological condition. Daily C-peptide urinary excretion may be a physiological index of IS, because C-peptide is co-secreted with insulin as a function of nutrient intake and IS. The amount of (2)H(2)O released from glycolytic glucose metabolism after [6,6-(2)H(2)]-glucose ingestion was recently proposed as a physiological measure of IS. We compared these IS surrogates to the gold standard (euglycemic-hyperinsulinemic clamp). Thirty (15 male/15 female) sedentary, nondiabetic participants (27.2 +/- 4.0 (s.d.) kg/m(2), 35 +/- 12 years) were admitted for 3 days to our in-patient unit. After a 10-h fast, they received 60 g of glucose and 15 g of [6,6-(2)H(2)]-glucose. Before glucose ingestion and hourly thereafter for 4 h, plasma glucose and insulin concentrations, and plasma deuterium enrichment were determined. Plasma (2)H(2)O production divided by insulin response was used as the glycolytic index. On day 2, subjects spent 23 h in a metabolic chamber (eucaloric diet, 50% carbohydrate, 30% fat). Urinary C-peptide excretion was divided by energy intake yielding the C-peptide to energy intake ratio (CPEP/EI). After leaving the chamber (day 3, 10-h fast), IS was measured by a 2-h clamp (120 mU/m(2)/min). Average IS (clamp) was 7.3 +/- 2.6 mg glucose/kg estimated metabolic body size/min (range: 3.6-13.2). These values were inversely correlated with CPEP/EI (r = -0.62; P < 0.01) and positively with the glycolytic rate (r = 0.60; P < 0.01). In nondiabetic subjects, two novel estimates of IS--daily urinary C-peptide urinary excretion and glycolytic rate during an oral glucose tolerance test --were related to IS by a clamp.