c-peptide and Neoplasms

A substantial body of evidence links sex hormones, diet, excess body weight and physical activity to the risk of developing cancer at several sites common in affluent countries. The hypothesis that high circulating levels of insulin could be the underlying factor increasing cancer risk has been proposed. Epidemiological studies on markers of hyper-insulinaemia and cancer are reviewed and summarized.. Studies of cancers of the colon and rectum, pancreas, breast, and endometrium examining the association with blood levels of C-peptide, insulin, glucose, glycated haemoglobin (HbA1c) were searched in PubMed. Multivariate, adjusted relative risks (RR) and their 95% confidence intervals were abstracted and summarized by meta-analyses.. Most of the studies identified were cohorts that relied on measurements obtained at baseline or assessed in blood stored at low temperature several years before the onset of cancer. The meta-analyses showed excess risks of colorectal and pancreatic cancers associated with higher levels of circulating C-peptide/insulin and with markers of glycaemia. Significant heterogeneity was found among four epidemiological studies of endometrial cancer and C-peptide giving a summary RR compatible with no association. Overall breast cancer risk was significantly higher in the upper categories of C-peptide/insulin, however, the excess derived entirely from retrospective studies.. Current evidence suggests that subjects who develop colorectal and pancreatic cancers have increased pre-diagnostic blood levels of insulin and glucose.

Topics: Biomarkers; Blood Glucose; C-Peptide; Humans; Hyperinsulinism; Insulin; Neoplasms

Gut peptide secreting tumours originate most commonly from the pancreatic Islets of Langerhans. Tumours at a variety of other sites have also been shown to synthesize and release these peptides, reflecting the wide distribution of the peptide secreting cells of the diffuse neuroendocrine system. Tumours such as the glucagonomas, insulinomas, VIPomas and gastrinomas are associated with characteristic clinical syndromes resulting from the effects of the peptide they secrete. The majority of the islet cell tumours in fact secrete a number of different peptides and many of these are present in several molecular forms, some of which may not be biologically active. This may explain the lack of clinical sequelae in association with tumours such as the somatostatinomas. The clinical features, methods of diagnosis, localisation and treatment of these tumours will be discussed.

Topics: Adenoma, Islet Cell; Bombesin; Bronchial Neoplasms; C-Peptide; Carcinoma, Small Cell; Diagnosis, Differential; Endocrine System Diseases; Erythema; Gastrointestinal Hormones; Glucagon; Glucagonoma; Humans; Insulin; Insulin Secretion; Insulinoma; Male; Neoplasms; Neurotensin; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatic Polypeptide; Somatostatinoma; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

We assessed the association between insulin resistance and blood glucose concentrations at type 2 diabetes diagnosis and future development of diabetes-related complications and mortality.. This retrospective cohort study included 864 individuals with type 2 diabetes (median age 60 years) whose fasting C-peptide and HbA1c were measured at diabetes diagnosis. The median follow-up time until death or study end was 16.4 years (interquartile range 13.3-19.6). The association between C-peptide and mortality/complications was estimated by Cox regression adjusted for sex, age at diabetes diagnosis, smoking, hypertension, BMI, total cholesterol, and HbA1c. C-peptide and HbA1c were converted to Z scores before the Cox regression analysis.. An increase by one standard deviation in fasting C-peptide at diabetes diagnosis was associated with all-cause (hazard ratio [HR] 1.33; 95% confidence intervals [CI] 1.12-1.58; p = 0.001) and cancer mortality (HR 1.51; 95% CI 1.13-2.01; p = 0.005) in the fully adjusted model. An increase by one standard deviation in HbA1c at diabetes diagnosis was associated with all-cause mortality (HR 1.24; 95% CI 1.07-1.44; p = 0.005), major cardiovascular events (HR 1.20; 95% CI 1.04-1.39; p = 0.015), stroke (HR 1.36; 95% CI 1.09-1.70; p = 0.006), and retinopathy (HR 1.54; 95% CI 1.34-1.76; p < 0.0001) in the fully adjusted model.. Fasting C-peptide at type 2 diabetes diagnosis is an independent risk factor for total and cancer-related mortality. Thus, treatment of type 2 diabetes should focus not only on normalising blood glucose levels but also on mitigating insulin resistance.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Glycated Hemoglobin; Humans; Middle Aged; Neoplasms; Retrospective Studies; Risk Factors

Immune checkpoint inhibitor (ICI) associated diabetes is a harmful adverse event (AE) in patients with cancer following anti-programmed (cell) death protein-1 (PD-1) treatment. There are no available biomarkers able to predict this AE. The primary aim of this study was to investigate C-peptide levels as potential predictor for the occurrence of ICI-related diabetes. The secondary aim was to describe the presence of islet autoantibodies and course of pancreatic enzymes in patients with and without ICI-related diabetes.. From a total of 1318 patients with cancer who started anti-PD-1 treatment 8 cases and 16 controls were studied in this nested case-control study. C-peptide levels, islet autoantibodies, and pancreatic enzymes were measured in prospectively collected blood serum.. In cases versus controls, median C-peptide levels were comparable at baseline and before toxicity or at the corresponding time point in controls. No patient had C-peptide levels below reference range before toxicity onset. Two out of eight patients in the ICI-related diabetes group had positive islet autoantibodies, whereas one out of 16 patients in the control group had positive islet autoantibodies. Pancreatic enzymes were elevated before diabetes onset in one patient (13%) and in one control (6%) at the corresponding time point.. In patients developing ICI-related diabetes, changes in C-peptide levels, islet autoantibody positivity, and pancreatic enzymes before ICI-related diabetes onset seem comparable to patients without ICI-related diabetes. (NTR: NL6828).

Topics: Autoantibodies; C-Peptide; Case-Control Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Neoplasms

The influence of type 2 diabetes mellitus (T2D) duration on cancer incidence remains poorly understood.. We prospectively followed for cancer incidence 113 429 women in the Nurses' Health Study (1978-2014) and 45 604 men in the Health Professionals Follow-up Study (1988-2014) who were free of diabetes and cancer at baseline. Cancer incidences were ascertained by review of medical records.. In the multivariable-adjusted model incident, T2D was associated with higher risk of cancers in the colorectum, lung, pancreas, esophagus, liver, thyroid, breast, and endometrium. The pooled hazard ratios (HRs) ranged from 1.21 (95% confidence interval [CI] = 1.06 to 1.38) for colorectal cancer to 3.39 (95% CI = 2.24 to 5.12) for liver cancer. For both composite cancer outcomes and individual cancers, the elevated risks did not further increase after 8 years of T2D duration. The hazard ratio for total cancer was 1.28 (95% CI = 1.17 to 1.40) for T2D duration of 4.1-6.0 years, 1.37 (95% CI = 1.25 to 1.50) for 6.1-8.0 years, 1.21 (95% CI = 1.09 to 1.35) for 8.1-10.0 years, and 1.04 (95% CI = 0.95 to 1.14) after 15.0 years. In a cross-sectional analysis, a higher level of plasma C-peptide was found among participants with prevalent T2D of up to 8 years than those without T2D, whereas a higher level of HbA1c was found for those with prevalent T2D of up to 15 years.. Incident T2D was associated with higher cancer risk, which peaked at approximately 8 years after diabetes diagnosis. Similar duration-dependent pattern was observed for plasma C-peptide. Our findings support a role of hyperinsulinemia in cancer development.

Topics: Adult; Aged; C-Peptide; Cohort Studies; Confidence Intervals; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Health Surveys; Humans; Incidence; Life Style; Male; Middle Aged; Neoplasms; Obesity; Proportional Hazards Models; Prospective Studies; Risk Factors; Time Factors; United States

To elucidate the individual impacts of insulin and blood glucose on cancer risk, we investigated the association of plasma C-peptide, a surrogated marker of insulin and glycated albumin (GA), a more stable marker of blood glucose, with all-site and site-specific cancer risk by mutually accounting for their confounding effects. The study was prospectively conducted with nearly 4,000 cancer cases arising in our population-based cohort of 33,736 subjects who answered the baseline questionnaire and supplied blood samples. After exclusion of subjects with apparent DM, analysis was done in 3,036 cancer cases and 3,667 subcohort subjects. Among men and women combined, highest levels of C-peptide were statistically significantly associated with an increased risk of all-site [Hazard ratio (HR): 1.21; 95% confidence interval: 1.02-1.42], colon [1.73; 1.20-2.47], liver [3.23; 1.76-5.91], kidney, renal pelvis and ureter cancers [2.47; 1.07-5.69], compared to the respective lowest levels, after adjustment for GA levels. Among these C-peptide-related cancers, colon and liver cancers also showed an increased risk associated with elevated GA levels independently of C-peptide levels. The corresponding HRs for colon and liver cancers compared to the highest and lowest GA levels were 1.43 [1.02-2.00] and 2.02 [1.15-3.55], respectively. Effect modification by gender was only evident for the association between C-peptide and colon cancer (p for interaction = 0.04). Higher insulin levels, independently of higher blood glucose levels, may be relevant to DM-related carcinogenesis for several cancer sites. Examination of circulating insulin levels is a plausible option in evaluating cancer risk even in individuals who have not developed DM.

Topics: Adult; Age Factors; Asian People; C-Peptide; Female; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Japan; Male; Middle Aged; Neoplasms; Prospective Studies; Risk Assessment; Risk Factors; Serum Albumin; Surveys and Questionnaires

Despite evidence that prolonged periods of sitting may influence biological mediators of cancer development, few studies have considered these relationships in a cancer-specific context.. This cross-sectional study included 755 postmenopausal women enrolled in an ancillary study of the Women's Health Initiative. Plasma levels of Insulin-like growth factor-I (IGF-I), IGF-binding protein-3, leptin, insulin, C-peptide, C-reactive protein (CRP), and Interleukin (IL)-6 were measured. The time spent sitting per day was categorized as quartiles (Qs). The relationships between sedentary time and biomarkers were modified by race, physical activity, and exogenous estrogen use.. IGF-I levels among African American (AA) women were higher than those of white women across the Qs of sedentary time. Likewise, IL-6 levels in AA women were higher than those in white women at Q3 and Q4 of sedentary time. IGFBP-3 levels were higher and insulin levels were lower across the Qs of sedentary time among women meeting guidelines for physical activity than women who were not. Additionally, CRP levels were higher among estrogen users than nonusers at Q1, Q2, and Q4 of sedentary time.. These results suggest that relationship between time spent sitting and cancer-related biomarkers may not be simply linear, but differ in the context of effect modifiers.

Topics: Aged; Biomarkers, Tumor; Black or African American; C-Peptide; C-Reactive Protein; Cross-Sectional Studies; Estrogen Replacement Therapy; Female; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Middle Aged; Neoplasms; Postmenopause; Sedentary Behavior; United States; White People; Women's Health

Known associations between diabetes and cancer could logically be attributed to hyperglycemia, hypersecretion of insulin, and/or insulin resistance. This study examined the relationship between initial glycemic biomarkers among men and women with impaired fasting glucose or undiagnosed diabetes and cancer mortality during follow up.. The cohort included subjects aged 40 years and above from the Third National Health and Nutrition Examination Survey (NHANES III) with fasted serum glucose >100 mg/dl without the aid of pharmaceutical intervention (insulin or oral hypoglycemics). Cancer mortality was obtained from the NHANES III-linked follow-up database (up to December 31, 2006). A Cox regression model was applied to test for the associations between cancer mortality and fasting serum glucose, insulin, glycosylated hemoglobin (HbA1c), C-peptide, insulin like growth factor (IGF-1), IGF binding protein 3 (IGFBP3) and estimated insulin resistance.. A total of 158 and 100 cancer deaths were recorded respectively from 1,348 men and 1,161 women during the mean 134-month follow-up. After adjusting for the effect of age and smoking in women, all-cause cancer deaths (HR: 1.96 per pmol/ml, 95% CI: 1.02-3.77) and lung cancer deaths (HR: 2.65 per pmol/ml, 95% CI: 1.31-5.36) were specifically associated with serum C-peptide concentrations. Similar associations in men were not statistically significant. Serum glucose, HbA1c, IGF-1, IGFBP3 and HOMA were not independently related to long-term cancer mortality.. C-peptide analyses suggest a modest association with both all-cause and lung cancer mortality in women but not in men. Further studies will be required to explore the mechanisms.

Topics: Adult; Aged; Biomarkers; C-Peptide; Cohort Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prediabetic State; Prognosis; Risk Factors; Smoking; Survival Rate

Insulin and glucose may influence cancer mortality via their proliferative and anti-apoptotic properties. Using longitudinal data from the nationally representative Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994), with an average follow-up of 8.5 years to death, we evaluated markers of glucose and insulin metabolism, with cancer mortality, ascertained using death certificates or the National Death Index. Plasma glucose, insulin, C-peptide, and lipid concentrations were measured. Anthropometrics, lifestyle, medical, and demographic information was obtained during in-person interviews. After adjusting for age, race, sex, smoking status, physical activity, and body mass index, for every 50 mg/dl increase in plasma glucose, there was a 22% increased risk of overall cancer mortality. Insulin resistance was associated with a 41% (95% confidence interval (CI) (1.07-1.87; p = 0.01) increased risk of overall cancer mortality. These associations were stronger after excluding lung cancer deaths for insulin-resistant individuals (HR: 1.67; 95% CI: 1.15-2.42; p = 0.01), specifically among those with lower levels of physical activity (HR: 2.06; 95% CI: 1.4-3.0; p = 0.0001). Similar associations were observed for other blood markers of glucose and insulin, albeit not statistically significant. In conclusion, hyperglycemia and insulin resistance may be 'high-risk' conditions for cancer mortality. Managing these conditions may be effective cancer control tools.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; Female; Glucose; Health Surveys; Humans; Insulin; Insulin Resistance; Life Style; Lipids; Longitudinal Studies; Male; Middle Aged; Neoplasms; Nutrition Surveys; Survival Rate; Time Factors; United States; Young Adult

Circulating insulin-like growth factor binding protein 1 (IGFBP-1), leptin, and insulin are 3 proteins modified by obesity and have been associated with cancer at several sites in past studies. We conducted a cross-sectional study to describe the correlation of these proteins with gender, race/ethnicity, anthropometric indexes, and dietary and lifestyle factors. We measured fasting plasma levels of IGFBP-1, leptin, and C-peptide, used here as a stable measure of insulin secretion, in a random sample of 450 male and 352 postmenopausal female Hawaii and Los Angeles Multiethnic Cohort Study (MEC) participants (age range 47-82 yr at blood draw). Through a series of multiple linear regressions, we found that the most parsimonious model for plasma IGFBP-1 included inverse associations with age, body mass index (BMI), and regular soda intake. A term for interaction between age and BMI was positively associated with plasma IGFBP-1. Adjusted mean plasma leptins were highest among Whites and African Americans and lowest among Hawaiians and Japanese Leptin was also inversely associated with age and positively associated with the interaction between age and race/ethnicity, female gender, and BMI. A model with only race/ethnicity and BMI (positive association) was best for plasma C-peptide. Adjusted means for C-peptide were highest for Japanese and Whites and lowest for African Americans. The overall percent of variance in protein levels explained by these models was low for IGFBP-1(R2=0.17) and C-peptide (R(3)=0.11) and higher for leptin (R(2)=0.57). We saw no clear correlation between racial/ethnic trends in protein levels with those of colorectal, breast, or prostate cancer incidence rates in the MEC. Research to clarify factors associated with determination of these proteins and their relationship with cancer etiology is warranted.

Topics: Age Factors; Aged; Aged, 80 and over; Asian; Black or African American; Body Mass Index; C-Peptide; Carbonated Beverages; Cohort Studies; Cross-Sectional Studies; Diet; Ethnicity; Female; Humans; Insulin; Insulin Secretion; Insulin-Like Growth Factor Binding Protein 1; Leptin; Life Style; Male; Middle Aged; Neoplasms; Obesity; White People

To compare the outcome of different treatment options used in several cases of non-islet cell tumour hypoglycaemia (NICTH).. Eight cases of NICTH were referred for diagnosis and monitoring following either surgical or medical treatment.. Serum samples collected throughout the time-course of each case were analysed for glucose, insulin, C-peptide, IGF-I, total IGF-II, total IGF-II to IGF-I ratio and, in most of the cases, big IGF-II.. Surgical excision was successful in the relief of symptoms and normalization of the biochemical parameters. Therapeutic treatment with glucocorticoids confirmed previous studies showing the suppressive effect on tumour (big) IGF-II production. The present data show that the effect was dose-dependent and reversible if doses were below a critical level.. Within the limits of the cases studied, and the time-scales involved, moderate- to high-dose glucocorticoid therapy had immediate beneficial influence on symptomatic hypoglycaemia and, if tolerated in the long term, was effective in correcting the underlying biochemical dysfunction, unlike other therapeutic regimens. This effectiveness was only achieved when the dose exceeded a threshold level specific to the patient. In addition, reduction of the dose or withdrawal of the drug caused a return of the abnormal biochemical profile. Surgical removal of the malignancy, where this was an option, was successful within the periods studied.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; C-Peptide; Female; Glucocorticoids; Human Growth Hormone; Humans; Hypoglycemia; Insulin; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male; Middle Aged; Neoplasms; Prednisolone; Protein Precursors

Excessive energy intake tends to increase circulating levels of insulin and free insulin-like growth factor-1 (IGF-I), which may increase risk of some cancers that are common in Western countries. However, the relative importance of these hormonal factors during pre-adulthood and adulthood is unknown.. We prospectively examined height, as a marker of pre-adult IGF-I bioactivity, and modifiable adult determinants of insulin secretion, in relation to risk of cancer, particularly Western-related cancers (colon, pancreas, kidney, and aggressive prostate cancers) in 47,690 male health professionals. Information about dietary and lifestyle factors for these men was collected at baseline (1986) and was updated periodically. A C-peptide score, representing insulin secretion, was created by using body mass, physical activity, and diet in a stepwise linear regression to predict C-peptide level, in a sample of 263 cohort members.. From 1986 to 1998, we documented 3270 incident cancers (excluding the less aggressive prostate cancers). Greater body mass index, lower physical activity, and a Western dietary pattern were independent predictors of higher plasma C-peptide levels in the sample. A C-peptide score, based on these variables, was positively related to risk of Western-related cancers, but not to other cancer types in the entire cohort. Height was also only related to Western-related cancers. For Western-related cancers, 29% (95% CI: 16%, 48%) were attributed to C-peptide scores above the first decile, 30% (95% CI: 11%, 58%) to heights >or=66 inches, and 49% (95% CI: 30%, 69%) to both factors combined. For total cancers, 29% (95% CI: 16%, 46%) were attributable to both factors.. Maximal growth in the pre-adult period and hyperinsulinaemia during adulthood may largely underlie the excess risk of some cancers that are common in Western populations. A substantial proportion of these cancers may be modifiable in adulthood, through alterations in body weight, sedentary behaviour, and dietary patterns that stimulate hyperinsulinaemia.

Topics: Adult; Aged; Body Height; Body Mass Index; C-Peptide; Diet; Exercise; Humans; Insulin; Insulin-Like Growth Factor I; Male; Middle Aged; Neoplasms; Prospective Studies; Prostatic Neoplasms; Risk Factors; United States

This study aims to identify the lifestyle determinants of insulin-like growth factor-I (IGF-I) and its main binding proteins (IGFBPs), C-peptide, and sex hormone-binding globulin (SHBG) to help elucidate the mechanism through which lifestyle factors may affect cancer risk.. This study is based on a sample of 292 British women, aged 20-70 years, whose lifestyle characteristics were assessed using a self-administered questionnaire and whose serum hormone concentrations were measured using immunoassays.. Age was a strong determinant of both IGF-I and IGFBP levels; women aged 65-70 years had significantly lower IGF-I and IGFBP-3 concentrations and significantly higher IGFBP-1 and IGFBP-2 concentrations than women aged 20-24 years. Body mass index (BMI) was not strongly associated with IGF-I, although women with a BMI of 26-27.9 kg/m2 had a higher IGF-I concentration compared with both lean (BMI <20 kg/m2) and obese (BMI 30+ kg/m2) women. However, obese women had a significantly higher C-peptide and IGFBP-3 concentration and a significantly lower IGFBP-1, IGFBP-2, and SHBG concentration compared with lean women. Increasing vigorous exercise was associated with a significantly lower C-peptide concentration and increasing leisure-time activity was associated with a significantly higher IGFBP-1 concentration. Other lifestyle factors such as job activity, smoking, and reproductive factors were not associated with any hormone.. Our data show that age is a major determinant of both IGF-I and its main binding proteins in women. BMI has strong effects on IGFBPs, C-peptide, and SHBG, but its effects on IGF-I remain unclear. The possible effect of physical activity on IGFBP-1 requires further investigation.

Topics: Adult; Age Factors; Body Mass Index; C-Peptide; Female; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Life Style; Middle Aged; Motor Activity; Neoplasms; Risk; Sex Hormone-Binding Globulin; United Kingdom

As part of a prospective diagnostic protocol, patients suspected of having pancreatic cancer had systemic and portal venous blood samples assayed, in coded batches, for peptide hormones and enzymes thought to be of potential value as tumor markers. An average of 111 patients were tested for each candidate marker. Results were analyzed by dividing patients into three groups according to the definitive diagnoses. These were pancreatic cancer (32% of patients), other cancers (27%), and benign diseases (41%). Although elevated mean levels of fasting plasma glucose and serum alkaline phosphatase were found in the pancreatic cancer group, there were no significant differences in the mean levels of any of the candidate markers studied in the three groups. The diagnostic values of normal and elevated levels of each candidate marker studied have been calculated. None has proven to be as useful as the serum level of pancreatic oncofetal antigen, fasting plasma glucose, or serum alkaline phosphatase in the diagnosis or exclusion of pancreatic cancer.

Topics: Alkaline Phosphatase; C-Peptide; Calcitonin; Chorionic Gonadotropin; Clinical Enzyme Tests; Clinical Laboratory Techniques; Evaluation Studies as Topic; Gastrins; Glucagon; Hormones; Humans; Insulin; Neoplasms; Pancreatic Neoplasms; Parathyroid Hormone; Prospective Studies; Ribonucleases