Urinary C-peptide Research Articles

Serum Osteocalcin/Bone-Specific Alkaline Phosphatase Ratio Is a Predictor for the Presence of Vertebral Fractures in Men with Type 2 Diabetes

We examined whether or not BMD or bone markers were useful for assessing the risk of vertebral fractures in 248 Japanese men with type 2 diabetes. We analyzed the relationships between bone markers (osteocalcin [OC], bone-specific alkaline phosphatase [BAP], urinary N-terminal cross-linked telopeptide of type-I collagen) or BMD and HbA(1c), urinary C-peptide, insulin-like growth factor-I (IGF-I), parathyroid hormone, 1,25(OH)(2) vitamin D, and the presence of prevalent vertebral fractures. Multiple regression analysis adjusted for age, body height, weight, duration of diabetes, and serum creatinine showed that serum OC and OC/BAP ratio were correlated negatively with HbA(1c) (P < 0.01) and positively with IGF-I (P < 0.01). Multivariate logistic regression analysis adjusted for the above parameters showed that serum OC/BAP ratio was inversely associated with the presence of vertebral fractures (odds ratio = 0.695, P < 0.05). This association was still significant after additional adjustment for lumbar or femoral neck BMD. Our results suggest that poor diabetic control and lower IGF-I level are linked to impaired bone formation and resultant reduction in OC/BAP ratio in men with type 2 diabetes. The OC/BAP ratio could be clinically useful for assessing the risk of vertebral fractures independent of BMD in diabetic men.

Laparoscopic Surgery Improves Blood Glucose Homeostasis and Insulin Resistance Following Distal Gastrectomy for Cancer

Prevention of blood glucose elevation and insulin resistance could be more pronounced in patients undergoing laparoscopic rather than open gastrectomy. Fifty-seven patients underwent distal gastrectomy by either laparoscopy (n = 36) or an open approach (n = 21). Blood glucose, serum insulin, and the daily insulin secretion rate (urinary C-peptide) were measured. Insulin resistance was evaluated using an adapted homeostasis model assessment of insulin resistance (HOMA-R). Blood glucose levels were lower in the laparoscopy group than in the open group on the operative day and on postoperative days (POD) 1 and 3 (P < .001, P = .001, and P = .024, respectively). Serum insulin levels were lower in the laparoscopy group than in the open group on POD 1 and 3 (P = .045 and P = .027, respectively). HOMA-R was lower in the laparoscopy group than in the open group on POD 1 and 3 (P = .024 and P = .009, respectively). Daily insulin secretion rates were lower in the laparoscopy group than in the open group on POD 1 (P = .023). Laparoscopic surgery prevents blood glucose elevation and improves insulin resistance compared with open surgery.

2型糖尿病におけるインスリン治療の要否判定の指標としての尿中Cペプチド補正値(UCC)およびCペプチドインデックス(CPI)の有用性

2型糖尿病におけるインスリン治療の要否判定の指標としての尿中Cペプチド補正値(UCC)およびCペプチドインデックス(CPI)の有用性

Associations between components of the metabolic syndrome versus bone mineral density and vertebral fractures in patients with type 2 diabetes

The association of bone with the metabolic syndrome and its features, visceral fat accumulation or insulin resistance, remains unclear. We determined visceral and subcutaneous fat areas (V and S) by computed tomography on 187 men (28–83 years) and 125 postmenopausal women (46–82 years) with type 2 diabetes. Men whose V was 100 cm2 or more had significantly lower urinary N-terminal cross-linked telopeptide of type-I collagen (p=0.005), higher femoral neck bone mineral density (FN-BMD) (p=0.004), and lower prevalence of vertebral fractures (VFs) (p=0.04) than controls. Fat mass, V, S, and lean body mass positively correlated with FN-BMD in men and with lumbar (L) and FN-BMD in women. When adjusted for weight, these correlations became negative. Urinary C-peptide positively correlated with FN-BMD in both genders. Multivariate logistic regression analysis adjusted for age, height, weight, L-BMD, duration of diabetes, and diabetes therapies identified V in men and urinary C-peptide in women as factors inversely associated with the presence of VFs [odds ratio (OR)=0.61 per SD increase, p=0.04, and OR=0.32, p=0.01, respectively]. These findings suggest that, of the components of the metabolic syndrome, body fat in gravity and hyperinsulinemia could increase FN-BMD in diabetic subjects. Visceral fat in men and hyperinsulinemia in women may protect against VFs independent of weight, L-BMD, diabetes duration, or therapies.

Urinary C-peptide tracks seasonal and individual variation in energy balance in wild chimpanzees

C-peptide of insulin presents a promising new tool for behavioral ecologists that allows for regular, non-invasive assessment of energetic condition in wild animals. C-peptide is produced on an equimolar basis with insulin, thus is indicative of the body's response to available glucose and, with repeated measurement, provides a biomarker of energy balance. As yet, few studies have validated the efficacy of C-peptide for monitoring energy balance in wild animals. Here, we assess seasonal and interindividual variation in urinary C-peptide concentrations of East African chimpanzees ( Pan troglodytes schweinfurthii). We assayed 519 urine samples from 13 adult male chimpanzees in the Kanyawara community of Kibale National Park, Uganda. C-peptide levels were significantly predicted by the total amount of fruit and the amount of preferred fruit in the diet. However, chimpanzees had very low C-peptide titers during an epidemic of severe respiratory illness, despite highly favorable feeding conditions. Kanyawara males had significantly lower C-peptide levels than males at Ngogo, a nearby chimpanzee community occupying a more productive habitat. Among Kanyawara males, low-ranking males had consistently higher C-peptide levels than dominant males. While counterintuitive, this result supports previous findings of costs associated with dominance in male chimpanzees. Our preliminary investigations demonstrate that C-peptide has wide applications in field research, providing an accessible tool for evaluating seasonal and individual variation in energetic condition, as well as the costs of processes such as immune function and reproduction.

Immunological Insulin Resistance Due to Insulin Antibodies Developed After Cessation of Insulin Therapy in a Patient With Type 2 Diabetes

While insulin antibodies reportedly exist in about half of patients with type 2 diabetes who inject insulin, these antibodies do not often severely affect blood glucose levels (1). Here, we report a patient who had insulin antibodies against human insulin and developed insulin resistance after episodes of frequent hypoglycemic attacks, even though insulin therapy had been discontinued. A 68-year-old Japanese male was referred to our hospital because of hyperglycemia in October 2003. He weighed 89 kg, and his height was 171 cm. His levels of fasting plasma glucose, A1C, and urine C-peptide immunoreactivity were 313 mg/dl, 10.6%, and 38.7 μg/day, respectively. Anti-GAD antibody …

Combination of Obesity with Hyperglycemia is a Risk Factor for the Presence of Vertebral Fractures in Type 2 Diabetic Men

Although patients with type 2 diabetes show no bone mineral density (BMD) reduction, fracture risks are known to increase. It is unclear why the patients have an increased risk of fracture despite sufficient BMD. We investigated the relationships of body mass index (BMI), HbA(1c), and urinary C-peptide (uC-peptide) versus BMD, bone metabolic markers, serum adiponectin, and prevalent vertebral fracture (VF). A total of 163 Japanese type 2 diabetic men were consecutively recruited, and radiographic and biochemical data were collected. BMI was positively correlated with BMD at the whole body, lumbar spine, and femoral neck (P < 0.05) and negatively correlated with osteocalcin and urinary N-terminal cross-linked telopeptide of type-I collagen (uNTX) (P < 0.01). HbA(1c) was negatively correlated with osteocalcin (P < 0.01) but not BMD at any site. Subjects were classified into four groups based on BMI and HbA(1c) (group LL BMI < 24 and HbA(1c) < 9, group LH BMI < 24 and HbA(1c) > or = 9, group HL BMI > or = 24 and HbA(1c) < 9, group HH BMI > or = 24 and HbA(1c) > or = 9). Serum adiponectin, osteocalcin, and uNTX were lower and the incidence of VF was higher despite sufficient BMD in the HH group. Multivariate logistic regression analysis adjusted for age, duration of diabetes, uC-peptide, and estimated glomerular filtration rate showed that the HH group was associated with the presence of a VF and multiple VFs (odds ratio [OR] = 3.056, 95% confidence interval [CI] 1.031-9.056, P = 0.0439, and OR = 5.415, 95% CI 1.126-26.040, P = 0.0350, respectively). Combination of obesity with hyperglycemia was a risk factor for VF despite sufficient BMD in diabetic men.

Urinary C-peptide as a method for monitoring body mass changes in captive bonobos ( Pan paniscus)

In recent years methodological improvements have allowed for more precise estimates of nutrient intake in wild primates. However, estimates of energetic condition have remained relatively imprecise due to the difficulties of estimating digestive efficiency and energy expenditure in these animals. In the absence of a reliable intake-expenditure calculation, a method is needed that directly links changes in energetic condition, such as body mass, to physiological changes that can be detected via markers in body excretions such as urine or feces. One promising marker is C-peptide, a metabolic byproduct of insulin synthesis. Here we present the results of a food restriction experiment carried out in a group of captive bonobos ( Pan paniscus). We measured changes in food availability and body mass and determined urinary C-peptide levels with the help of a time-resolved fluoroimmunoassay routinely used for measuring C-peptide in human blood. Urinary C-peptide levels decreased during a period of food restriction and increased again when food availability was continuously increased. During this refeeding phase an increase in body mass was significantly correlated with an increase in urinary C-peptide levels. Our results suggest that urinary C-peptide levels are an accurate indicator of individual energy balance. In conclusion, measuring C-peptide in urine is a promising method to quantify the energetic condition of wild apes.

Effect of almonds on insulin secretion and insulin resistance in nondiabetic hyperlipidemic subjects: a randomized controlled crossover trial

Nuts appear to have a marked effect in cohort studies in reducing the risk of coronary heart disease (CHD), but their demonstrated ability to lower cholesterol can only explain a proportion of the reduction in risk. Our aim was to assess whether improvement in carbohydrate metabolism provides a further explanation for the effect of nuts in reducing CHD. The effects of whole almonds, taken as snacks, were compared with the effects of low saturated fat (<5% energy) whole-wheat muffins (control) in the therapeutic diets of hyperlipidemic subjects. In a randomized crossover study, 27 hyperlipidemic men and women consumed 3 isoenergetic (mean, 423 kcal/d) supplements each for 1 month. Supplements provided 22.2% of energy and consisted of full-dose almonds (73 ± 3 g/d), half-dose almonds plus half-dose muffins, and full-dose muffins. Subjects were assessed at weeks 0, 2, and 4 and fasting blood samples were obtained. Twenty-four-hour urinary output was collected at the end of week 4 on each treatment. Mean body weights differed by less than 300 g between treatments. No differences were seen in baseline or treatment values for fasting glucose, insulin, C-peptide, or insulin resistance as measured by homeostasis model assessment of insulin resistance. However, 24-hour urinary C-peptide output as a marker of 24-hour insulin secretion was significantly reduced on the half-and full-dose almonds by comparison to the control after adjustment for urinary creatinine output ( P = .002 and P = .004, respectively). We conclude that reductions in 24-hour insulin secretion appear to be a further metabolic advantage of nuts that in the longer term may help to explain the association of nut consumption with reduced CHD risk.

A case of fulminant type 1 diabetes mellitus after influenza B infection

A 64-years-old man referred to a hospital because of high-grade fever. He was diagnosed as having influenza B by “POCTEM Influenza A/B”, a rapid influenza diagnostic kit which detect some antigens of influenza virus. Six days after medication of oseltamivir phosphate, his flu-symptoms disappeared, but he complained sever thirsty. And after 2 days, he suffered from loss of consciousness and was admitted to the hospital. Laboratory data on admission showed diabetes ketoacidosis, slight elevation of HbA1c level despite sever hyperglycemia, and increase of serum amylase concentration. Anti GAD antibody and anti IA-2 antibody were not detected. Urinary C-peptide excretion was undetectable and serum C-peptide levels were also undetectable after glucagon and arginin load, suggesting disappearance of endogeneous insulin secretion. Class II HLA was susceptible to fulminant type1 diabetes. Based on these findings, we diagnosed him with fulminant type1 diabetes. In Japan, only three viruses in three cases have been reported to be the trigger in the development of fulminant type 1 diabetes. They were human herpes virus 6, herpes simplex virus and Coxsackie B3 virus. This is the fourth report of fulminant type 1 diabetes developed after the established diagnosis of viral infection and the first after influenza B virus infection. The fact that fulminant type 1 diabetes developed after the infection of such a common virus suggest that factors within host will play more important roles than virus itself in the etiology of fulminant type 1 diabetes.

A Case of Fulminant Type 1 Diabetes Associated With Significant Elevation of Mumps Titers

Type 1 diabetes mellitus is classified as either autoimmune or idiopathic. Fulminant type 1 diabetes was originally reported as a subtype of idiopathic type 1 diabetes. Though involvement of viral infections has been suggested as a triggering mechanism, its pathogenesis remains unknown. Here, we present a case of fulminant type 1 diabetes associated with significant elevation of mumps titers. A 56-year-old Japanese man had suffered from nausea and generalized fatigue for two days before being transferred to our hospital in a confused state. Findings on admission revealed a high blood glucose level, near-normal HbA1c level, metabolic acidosis, and increased urinary ketone levels. Serum tests for islet-associated autoantibodies were negative. The serum, urinary C-peptide levels and the result of glucagon test indicated severe impairment of insulin secretion. These results were compatible with the diagnosis of fulminant type 1 diabetes. Also, he was suspected as having mumps infection on the basis of serological testing. These findings suggest that fulminant type 1 diabetes developed after mumps virus infection in our case. To the best of our knowledge, no other report has indicated an association between a recent mumps infection and the onset of fulminant type 1 diabetes. This case suggests an association between fulminant type 1 diabetes and mumps virus infection.

Urinary C-peptide of insulin as a non-invasive marker of energy balance in wild orangutans

Assessment of energetic condition is a critical tool for behavioral and reproductive ecologists. However, accurate quantification of energy intake and expenditure is labor-intensive, and it can be problematic for field scientists to obtain regular data on individual animals. C-peptide, a polypeptide segment of the proinsulin molecule that is secreted along with insulin in an equimolar relationship, can be measured in urine, and thus offers a potential means for the non-invasive assessment of energy balance in wild animals. Here, we validate C-peptide for the quantification of energetic condition, with specific application to wild orangutans ( Pongo pygmaeus). We determined that application of urine to filter paper results in significantly lower C-peptide recoveries versus fresh samples. However, concentrations in filter paper samples were significantly correlated with fresh urine and were stable over various storage conditions and durations. We compared the C-peptide concentrations from wild orangutan urine samples with three independent measures of energetic condition: ketone bodies (urinalysis), caloric intake (nutritional biochemistry), and food availability (phenology). As expected, C-peptide concentrations were significantly lower in samples that tested positive for ketones in the field. Monthly average C-peptide concentrations of both male and female orangutans were significantly correlated with monthly determinations of energy intake and food availability. Therefore, we conclude that the collection and preservation of urine samples for C-peptide analysis are feasible under most field conditions and, in this species, presents a useful tool for assessing changes in energy balance.

Insulin administration may trigger pancreatic β-cell destruction in patients with type 2 diabetes

Insulin administration causes various types of immune response to insulin. However, there have been no reports that insulin administration triggers pancreatic β-cell destruction in diabetic patients. We evaluated three patients who had suffered from type 2 diabetes or impaired glucose tolerance for 5–30 years. After an episode of diabetic mononeuropathy or poor glycemic control, they started human insulin therapy. All the patients’ serum or urinary C-peptide levels were preserved before insulin therapy, whereas within a few months they rapidly declined to below detection limits. A high titer of insulin antibody was detected at or after the development of insulin deficiency. Shortly after the initiation of insulin therapy, two of the patients developed an insulin allergy. Autoantibodies to GAD65 or IA-2 were negative throughout the clinical course in two cases, but transiently positive in one case. In a histological examination of pancreas tissue obtained by a pancreatic biopsy in one case, mononuclear cell infiltration into the islets was observed. They all had a type 1 diabetes high-risk HLA class II haplotype in Japanese, and class I alleles of the insulin gene VNTR. The above findings suggest that insulin administration may have triggered pancreatic β-cell destruction in these patients.

Comparison of the alteration of the concentration of C-peptide in 24-h urine according to the combination patterns of hypoglycemic agents in type 2 diabetes patients

Aims Urinary C-peptide (UCP) has been considered as a simple method for monitoring beta-cell function in diabetic patients clinically. The aim of the study is to compare the changes of 24-h urinary C-peptide levels according to subgroups divided by therapeutic agents for subjects with type 2 diabetes. Methods In 206 participants, under treatment for type 2 diabetes, 24-h urinary C-peptide levels were assessed yearly for 3 years. All participants were subdivided into four groups according to the therapeutic agents. Changes for the measured values during the follow-up were compared between groups. Results Mean HbA1C was 7.1% and mean 24-h UCP was 61.7 μg/24 h and mean duration of diabetes was 8.7 years in all subjects at baseline. Mean 24-h UCP levels increased significantly from a baseline to at 36 months in the insulin sensitizers (IS) only group, in the IS plus sulfonylurea combination group and in IS plus insulin combination group ( p < 0.001), whereas in the sulfonylurea only group, we could not find statistically significant changes ( p = 0.152). Treatment with only IS significantly reduced fasting plasma glucose (FPG) and HbA1C level ( p = 0.045, p < 0.001). Differences between baseline and last 24-h UCP were significantly different between-groups and this difference was more significant after adjustment in FPG, HbA1C, and the duration of diabetes ( p = 0.024). Especially, IS plus sulfonylurea combination group resulted in greatest increase of 24-h UCP (ΔC-peptide = 51.19 μg/24 h). Conclusions This study suggested that IS, in mono- or in combination, significantly improved pancreatic beta-cell function, especially when combined with sulfonylurea as evidenced by the increase of 24-h UCP.

Live encapsulated porcine islets from a type 1 diabetic patient 9.5 yr after xenotransplantation

The long-term viability and function of transplanted encapsulated neonatal porcine islets was examined in a diabetic patient. A 41-yr-old Caucasian male with type 1 diabetes for 18 yr was given an intraperitoneal transplant of alginate-encapsulated porcine islets at the dose of 15,000 islet equivalents (IEQs)/kg bodyweight (total dose 1,305,000 IEQs) via laparoscopy. By 12 weeks following the transplant, his insulin dose was significantly reduced by 30% (P = 0.0001 by multiple regression tests) from 53 units daily prior to transplant. The insulin dose returned to the pre-transplant level at week 49. Improvement in glycaemic control continued as reflected by total glycated haemoglobin of 7.8% at 14 months from a pre-transplant level of 9.3%. Urinary porcine C-peptide peaked at 4 months (9.5 ng/ml) and remained detectable for 11 months (0.6 ng/ml). The patient was followed as part of a long-term microbiologic monitoring programme which subsequently showed no evidence of porcine viral or retroviral infection. At laparoscopy 9.5 yr after transplantation, abundant nodules were seen throughout the peritoneum. Biopsies of the nodules showed opacified capsules containing cell clusters that stained as live cells under fluorescence microscopy. Immunohistology noted sparse insulin and moderate glucagon staining cells. The retrieved capsules produced a small amount of insulin when placed in high glucose concentrations in vitro. An oral glucose tolerance test induced a small rise in serum of immuno-reactive insulin, identified as porcine by reversed phase high pressure liquid chromatography. This form of xenotransplantation treatment has the potential for sustained benefit in human type 1 diabetics.

Potential applications of urinary C‐peptide of insulin for comparative energetics research

The study of comparative energetics offers a valuable way to identify broad ecological principles and assess the functional significance of energetic adaptations during the course of evolution. Yet, the quantification of energetic status for nonhuman primates under natural conditions remains one of the most challenging aspects of comparative energetics research. Here, we report on the development of a noninvasive field method for measuring energetic status in great apes, humans, and possibly other nonhuman primates. Specifically, we have explored measurement of a urinary metabolite of insulin (C-peptide) as a physiological marker of energetic condition in chimpanzees and orangutans. We performed three validation studies and successfully measured C-peptide in urine samples from captive chimpanzees, wild chimpanzees, and wild orangutans. Urinary C-peptide measures gave indications of being a reliable signal of energetic status in both species. For chimpanzees and orangutans in the wild, baseline urinary C-peptide levels were higher during periods of fruit abundance than periods of low fruit availability. Urinary C-peptide levels were also higher for well-fed captive chimpanzees compared with wild chimpanzees. Although sample size was small, top-ranking male chimpanzees showed higher C-peptide levels in the wild than low-ranking males only during the period of fruit abundance. These preliminary results indicate that further development of the urinary C-peptide method could expand opportunities to quantify energetic condition for great apes in the wild and generate new data for comparative research. We highlight specific applications for studying great ape reproduction as well as the nutritional ecology of human foragers.

インスリン導入が遅れ高血糖高浸透圧昏睡を来たした高齢者糖尿病の1例

A 79-year old woman was admitted with disturbed consciousness (JCS II-30). She had been given a diagnosis of type 2 diabetes 7 years previously, and was being treated with oral hypoglycemic agents. She also suffered Alzheimer's disease and Parkinson's disease. Plasma glucose and HbA1c upon admission was 676mg/dl and 9.7%, respectively. Serum Na was 153mEq/l. Urine ketone body test was negative and metabolic acidosis was not observed. Hyperglycemic hyperosmolar non-ketotic coma (HHNC) was diagnosed, and treatment was started immediately with normal saline infusion. Continuous infusion of regular insulin was needed to lower blood glucose. Disturbed consciousness and dehydration improved by the third hospital day. However, she became bedridden afterwards and received tube feeding. Up to 46 units of insulin was needed daily to control blood glucose. Urine C-peptide secretion was very low (10microg/day), suggesting that insulin therapy was essential for glycemic control long before admission. It is thought that a number of elderly diabetic patients who need insulin therapy do not receive or continue it for various reasons. Discussion is necessary to grasp the actual situation and defensive actions that can be taken.

Changes in heart rate with refeeding in anorexia nervosa: A pilot study

Objective To find differences in heart rate before and after refeeding and to identify which parameters of autonomic activity and endocrine function are associated with these differences. Methods Before and after the start of refeeding, body weight, RR interval (RRI), heart rate variability, endocrine function, and energy expenditure were measured in nine female anorexia nervosa patients. Results After short-term refeeding, mean daytime heart rate rose from 54.9 to 69.4 bpm ( P<.05). The changes in sympathetic activity were correlated negatively with the changes in RRI ( r=−.933, P<.001). Urine C-peptide, IGF-1, and fT3 increased significantly, and norepinephrine tended to increase. Conclusion We demonstrated that autonomic nervous activity was relevant to changes in heart rate during refeeding, and it is speculated that the increases in insulin secretion, thyroid function, and IGF-1 were responsible for the mechanisms.

Acute onset of type 1 diabetes accompanied by acute hepatitis C: The potential role of proinflammatory cytokine in the pathogenesis of autoimmune diabetes

A 22-year-old Japanese woman presented with general fatigue. Five days later, she demonstrated a body temperature of 39 °C and a loss in weight of 5 kg. She thereafter became unconscious and was taken to Tomakomai City General Hospital. Urinary ketone body was positive, and plasma glucose was 1063 mg/dl. The serum asparate aminotransferase and alanine aminotransferase levels were 158 and 1220 IU/l, respectively. An arterial blood gas analysis showed metabolic acidosis. Glycated hemoglobin was 10.9%. Urinary C-peptide immnoreactivity was 11 μg/day. Anti-glutamic acid decarboxylase antibody was 12.4 U/ml. In general, islet-associated autoantibodies are detectable several years before the development of overt autoimmune diabetes, thus suggesting that an autoimmune reaction against β-cells had already started in this case. On viral examinations, hepatitis C virus (HCV) antibody was negative, while HCV-RNA was positive. Based on these findings, she was diagnosed to have autoimmune diabetes and acute hepatitis C. In addition, her serum interleukin-18 level was elevated to 506 pg/ml. The duration of diabetic characteristic symptoms before diagnosis is usually several weeks in most cases of autoimmune diabetes. However, it was extremely short in this case. Taken together, these findings suggested that the progression of autoimmune diabetes might have been accelerated due to the infection of HCV.

Urinary C-Peptide Excretion in Free-Living Healthy Children Is Related to Dietary Carbohydrate Intake but Not to the Dietary Glycemic Index

This study first examined whether urinary C-peptide (UCP), stored at -20 degrees C, remains stable over the long term, and second, whether the dietary glycemic index (GI) and the glycemic load (GL: GI x g carbohydrates) are related to the 24-h UCP excretion of healthy children. Participants in the Dortmund Nutrition and Anthropometric Longitudinally Designed Study with 24-h urine collections and a simultaneously completed weighed dietary record were included. From these, 3 comparable groups of 7- to 8-y-old children (n = 40 each) from 1990, 1996, and 2002 were randomly selected (total n = 120). C-peptide was measured with a 1-site ELISA. A GI value was assigned to all recorded foods containing carbohydrates (CHO). Statistical equivalence tests corroborated that UCP excretion in the 3 sampling periods was equivalent when corrected for body weight and protein intake (P < 0.05). UCP excretion was associated with the GL after adjustment for body weight, protein, and fiber intake [mean UCP (95% CI) in GL tertiles 1-3: 6.19 (5.37, 7.14) vs. 7.82 (6.77, 9.02) vs. 7.76 (6.71, 8.97) nmol/d, P for difference 0.04]. GI was not significantly related to UCP excretion [adjusted means (95% CI): 7.27 (6.28, 8.41) vs. 6.51 (5.64, 7.51) vs. 7.94 (6.86, 9.18), P for difference 0.2]. In conclusion, UCP retrospectively measured with a 1-site ELISA remained stable for up to 12 y (from 1990 until 2002). The observed positive relation of UCP with GL appears to result largely from its association with the amount of CHO, whereas dietary GI may be relevant only at higher intake levels.