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Background. A−β+ ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved β-cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at "T2D" onset and determined the prevalence and characteristics of pediatric A−β+ KPD within this cohort. Methods. We reviewed the records of 716 children with T2D at a large academic hospital and compared clinical characteristics of those with and without DKA at onset. In the latter group, we identified patients with A−β+ KPD using criteria of the Rare and Atypical Diabetes Network (RADIANT) and defined its prevalence and characteristics. Results. Mean age at diagnosis was 13.7 ± 2.4 years: 63% female; 59% Hispanic, 29% African American, 9% non-Hispanic White, and 3% other. Fifty-six (7.8%) presented with DKA at diagnosis and lacked islet autoantibodies. Children presenting with DKA were older and had lower C-peptide and higher glucose concentrations than those without DKA. Twenty-five children with DKA (45%) met RADIANT A−β+ KPD criteria. They were predominantly male (64%), African American or Hispanic (96%), with substantial C-peptide (1.3 ± 0.7 ng/mL) at presentation with DKA and excellent long-term glycemic control (HbA1c 6.6% ± 1.9% at follow-up (median 1.3 years postdiagnosis)). Conclusions. In children with a clinical phenotype of T2D and DKA at diagnosis, approximately half meet criteria for A−β+ KPD. They manifest the key characteristics of obesity, preserved β-cell function, male predominance, and potential to discontinue insulin therapy, similar to adults with A−β+ KPD. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is an autoimmune disease initiated by genetic predisposition and environmental influences, which result in the specific destruction of insulin‐producing pancreatic β‐cells. Currently, there are over 1.6 million cases of T1D in the United States with a worldwide incidence rate that has been increasing since 1990. Here, we examined the effect of Cornus officinalis (CO), a well‐known ethnopharmacological agent, on a T1D model of the non‐obese diabetic (NOD) mouse. A measured dose of CO extract was delivered into 10‐week‐old NOD mice by oral gavage for 15 weeks. T1D incidence and hyperglycemia were significantly lower in the CO‐treated group as compared to the water gavage (WT) and a no handling or treatment control group (NHT) following treatment. T1D onset per group was 30%, 60% and 86% for the CO, WT and NHT groups, respectively. Circulating C‐peptide was higher, and pancreatic insulitis was decreased in non‐T1D CO‐treated mice. Our findings suggest that CO may have therapeutic potential as both a safe and effective interventional agent to slow early stage T1D progression. [ABSTRACT FROM AUTHOR]

Objective: To examine whether proinflammatory and hyperinsulinemic diets are associated with increased risk of type 2 diabetes.Research Design and Methods: We prospectively followed 74,767 women from the Nurses' Health Study (1984-2016), 90,786 women from the Nurses' Health Study II (1989-2017), and 39,442 men from the Health Professionals Follow-up Study (1986-2016). Using repeated measures of food-frequency questionnaires, we calculated empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores, which are food-based indices that characterize dietary inflammatory or insulinemic potential based on circulating biomarkers of inflammation or C-peptide. Diagnoses of type 2 diabetes were confirmed by validated supplementary questionnaires.Results: We documented 19,666 incident type 2 diabetes cases over 4.9 million person-years of follow-up. In the pooled multivariable-adjusted analyses, individuals in the highest EDIP or EDIH quintile had 3.11 times (95% CI 2.96-3.27) and 3.40 times (95% CI 3.23-3.58) higher type 2 diabetes risk, respectively, compared with those in the lowest quintile. Additional adjustment for BMI attenuated the associations (hazard ratio 1.95 [95% CI 1.85-2.05] for EDIP and hazard ratio 1.87 [95% CI 1.78-1.98] for EDIH), suggesting adiposity partly mediates the observed associations. Moreover, individuals in both highest EDIP and EDIH quintiles had 2.34 times higher type 2 diabetes risk (95% CI 2.17-2.52), compared with those in both lowest quintiles, after adjustment for BMI.Conclusions: Higher dietary inflammatory and insulinemic potential were associated with increased type 2 diabetes incidence. Findings suggest that inflammation and hyperinsulinemia are potential mechanisms linking dietary patterns and type 2 diabetes development. [ABSTRACT FROM AUTHOR]

In the recently published consensus statement on the treatment and management of type 1 diabetes issued by experts from the American (ADA) and European (EASD) diabetes societies, measurement of endogenous insulin secretion using fasting C-peptide is recommended as a diagnostic criterion. In contrast, our group recently suggested fasting C-peptide/glucose ratio (CGR) for the determination of endogenous insulin secretion. In addition, this ratio may turn out as a potential decision aid for pathophysiologically based differential therapy of diabetes. In this comment, the following points will be discussed: i) CGR as the basis of differential diagnosis of type 1 diabetes, ii) CGR as the basis of treatment decisions for or against insulin in diabetes, and iii) the ease of application of CGR in clinical practice. The use of CGR may complement the ADA/EASD recommendations and should provide a practical application in clinical practice., Competing Interests: The authors declare that they have no conflict of conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

There is limited evidence on the association between plasma trans-fatty acids (TFAs) and cardiometabolic risk factors. Therefore, we examined the association between plasma TFA concentrations and glucose homeostasis and cardiovascular (CV) risk factors in adult Americans from the 1999 to 2000 National Health and Nutrition Examination Survey participants. Derivatized TFAs were separated by capillary gas chromatography. Of the 1678 participants, 46.5% were men. The mean age was 50.5 years overall, with no significant difference between men and women (P = .101). In age-, sex- and race-adjusted analyses, mean waist circumference, fat-free mass, fat mass, C-peptide, insulin, hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), serum triglycerides (TGs), and total cholesterol (TC) increased across increasing quarters of TFAs (for all P < .001), while mean serum high-density lipoprotein cholesterol decreased across increasing quarters of plasma TFAs (P < .001). In multivariable adjusted linear regressions, there remained significant positive associations between all plasma TFAs and body mass index, waist circumference, fat-free mass, fat mass, C-peptide, insulin, fasting blood glucose, HOMA-IR, HbA1c, TGs, low-density lipoprotein cholesterol, and TC (P < .001). In conclusion, our findings support a possible association between plasma TFAs concentrations and measures of glucose homeostasis and several CV risk factors. [ABSTRACT FROM AUTHOR]

Background: Healthful dietary patterns have been associated with lower risks of type 2 diabetes and coronary artery disease, but their relations with intermediate markers of cardiometabolic and endocrine health are less established. Objective: We evaluated the Dietary Approaches to Stop Hypertension (DASH), the alternate Mediterranean diet (aMED), and the Alternate Healthy Eating Index (aHEI) diet-quality scores with cardiometabolic and endocrine plasma biomarkers in US women. Design: The trial was a cross-sectional analysis of 775 healthy women in the Women's Lifestyle Validation Study that was conducted within the NHS (Nurses' Health Study) and NHS II longitudinal cohorts. Multiple linear regression models adjusted for potential confounders were used to estimate associations between quartiles of dietary pattern-adherence scores that were derived from a food-frequency questionnaire and plasma biomarker concentrations that were collected simultaneously. Results: In multivariable models in which highest and lowest quartiles of dietary pattern scores were compared, 1) DASH was significantly associated with higher concentrations of high-density lipoprotein (9%) and sex-hormone binding globulin (SHBG) (21%), and lower concentrations of leptin (28%), triglycerides (19%), and C-peptide (4%) (all P-trend ≤ 0.04); 2) the aMED was associated with 19% higher SHBG and 16% lower triglycerides (P-trend = 0.02 and 0.003, respectively); and 3) the aHEI was associated with significantly higher concentrations of insulin (16%) and SHBG (19%) and lower concentrations of leptin (18%) (all P-trend ≤ 0.02). Further adjustment for body mass index (BMI) attenuated these associations but remained significant for 1) DASH with leptin and triglycerides and 2) the aMED with triglycerides (all P-trend ≤ 0.03). Conclusions: Adherence to healthful dietary patterns is associated with favorable concentrations of many cardiometabolic and endocrine biomarkers. [ABSTRACT FROM AUTHOR]

Personalized medicine, otherwise called stratified or precision medicine, aims to better target intervention to the individual to maximize benefit and minimize harm. This review discusses how diabetes aetiology, pathophysiology and patient genotype influence response to or side effects of the commonly used diabetes treatments. C-peptide is a useful biomarker that is underused to guide treatment choice, severe insulin deficiency predicts non-response to glucagon-like peptide-1 receptor agonists, and thiazolidinediones are more effective in insulin-resistant patients. The field of pharmacogenetics is now yielding clinically important results, with three examples outlined: sulphonylurea sensitivity in patients with HNF1A maturity-onset diabetes of the young; sulphonylurea sensitivity in patients with Type 2 diabetes with reduced function alleles at CYP2C9, resulting in reduced metabolism of sulphonylureas; and severe metformin intolerance associated with reduced function organic cation transporter 1 ( OCT1) variants, exacerbated by drugs that also inhibit OCT1. Genome-wide approaches and the potential of other 'omics', including metagenomics and metabolomics, are then outlined, highlighting the complex interacting networks that we need to understand before we can truly personalize diabetes treatments. [ABSTRACT FROM AUTHOR]

Aim To determine whether the low C-peptide levels (< 50 pmol/l) produced by the pancreas for decades after onset of Type 1 diabetes have clinical significance. Methods We evaluated fasting C-peptide levels, duration of disease and age of onset in a large cross-sectional series ( n = 1272) of people with Type 1 diabetes. We then expanded the scope of the study to include the relationship between C-peptide and HbA1c control ( n = 1273), as well as diabetic complications ( n = 324) and presence of hypoglycaemia ( n = 323). The full range of C-peptide levels was also compared with 1,5-Anhydroglucitol, a glucose responsive marker. Results C-peptide levels declined for decades after diagnosis, and the rate of decline was significantly related to age of onset ( P < 0.0001), after adjusting for disease duration. C-peptide levels > 10 pmol/l were associated with protection from complications (e.g. nephropathy, neuropathy, foot ulcers and retinopathy; P = 0.03). Low C-peptide levels were associated with poor metabolic control measured by HbA1c ( P < 0.0001). Severe hypoglycaemia was associated with the lowest C-peptide levels compared with mild ( P = 0.049) or moderate ( P = 0.04) hypoglycaemia. All levels of measurable C-peptide were responsive to acute fluctuations in blood glucose levels as assessed by 1,5-Anhydroglucitol ( P < 0.0001). Conclusions Low C-peptide levels have clinical significance and appear helpful in characterizing groups at-risk for faster C-peptide decline, complications, poorer metabolic control and severe hypoglycaemia. Low C-peptide levels may be a biomarker for characterizing at-risk patients with Type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aim Serum C-peptide is an active peptide that has important physiological functions and characteristics in the elderly. The present study aimed to investigate the association between physical activity and serum C-peptide level independent of insulin level among the elderly. Methods The study included 1700 elderly participants aged ≥65 years. Stratified analysis of covariance was used to compare serum C-peptide levels in participants with different physical activity levels. Two separate multiple linear regression models were created to estimate the association between physical activity and serum C-peptide level. Results The results of analysis of covariance stratified by sex, body mass index and serum insulin level showed that those who engaged in vigorous physical activity had lower serum C-peptide levels than those who engaged in light or no physical activity. Separate multiple linear regression analysis showed that in those with low serum C-peptide levels (≤0.621 nmol/L), physical activity was significantly positively associated with the serum C-peptide level. In contrast, physical activity was negatively associated with the serum C-peptide level among those with serum C-peptide level >0.621 nmol/L. Conclusions The serum C-peptide level showed a significant two-way association with physical activity. The present findings suggest that physical activity modification is important for improving serum C-peptide levels among the elderly. Geriatr Gerontol Int 2014; 14: 647-653. [ABSTRACT FROM AUTHOR]

Prepubertal African American (AA) youth compared with their Caucasian (C) peers have higher insulin secretion, which correlates positively with free fatty acid (FFA) concentration. In our continued efforts to explain the racial disparity in insulinemia, and because FFAs modulate insulin secretion, we hypothesized that AA youth would have a greater response to FFA-induced β-cell insulin secretion than C youth. We compared the short-term effects of FFA elevation on fasting and glucose-stimulated C-peptide--modeled insulin secretion in prepubertal normal-weight AA versus C peers during a 2-h hyperglycemic clamp (12.5 mmol/L) on two occasions: 1) infusion of normal saline and 2) infusion of 20% intralipid (IL). During IL infusion, insulin sensitivity (IS) declined comparably in AA and C youth. Glucose sensitivity of first- and second-phase insulin secretion showed a significant condition x race interaction being higher in AA youth. Disposition index, β-cell function relative to IS, declined with IL infusion in AA and C youth, with a significantly greater decrease in Cs compared with AAs. In conclusion, AA and C prepubertal youth both demonstrated a decline in β-cell function relative to IS during IL infusion, indicative of acute lipotoxicity. The greater decline in C youth compared with AAs may suggest that C youth are more susceptible to β-cell lipotoxicity than AA youth, or alternatively, that AA youth are hypersensitive to FFA stimulation of β-cell insulin secretion, consistent with our theory. [ABSTRACT FROM AUTHOR]

Objective: To test the novel hypothesis that nutritional factors previously associated with type 1 diabetes etiology or with insulin secretion are prospectively associated with fasting C-peptide (FCP) concentration among youth recently diagnosed with type 1 diabetes.Research Design and Methods: Included were 1,316 youth with autoantibody-positive type 1 diabetes who participated in the SEARCH for Diabetes in Youth study (baseline disease duration, 9.9 months; SD, 6.3). Nutritional exposures included breastfeeding and age at introduction of complementary foods, baseline plasma long-chain omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), vitamin D, vitamin E, and, from a baseline food frequency questionnaire, estimated intake of the branched-chain amino acid leucine and total carbohydrate. Multiple linear regression models were conducted to relate each nutritional factor to baseline FCP adjusted for demographics, disease-related factors, and other confounders. Prospective analyses included the subset of participants with preserved β-cell function at baseline (baseline FCP ≥0.23 ng/mL) with additional adjustment for baseline FCP and time (mean follow-up, 24.3 months; SD, 8.2; n = 656). FCP concentration was analyzed as log(FCP).Results: In adjusted prospective analyses, baseline EPA (P = 0.02), EPA plus DHA (P = 0.03), and leucine (P = 0.03) were each associated positively and significantly with FCP at follow-up. Vitamin D was unexpectedly inversely associated with FCP (P = 0.002).Conclusions: Increased intake of branched-chain amino acids and long-chain omega-3 fatty acids may support preservation of β-cell function. This represents a new direction for research to improve prognosis for type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: Connecting peptide (C-peptide) plays a role in early atherogenesis in patients with diabetes mellitus and may be a marker for cardiovascular morbidity and mortality in patients without diabetes. We investigated whether serum C-peptide levels are associated with all-cause, cardiovascular-related and coronary artery disease-related mortality in adults without diabetes. Methods: We used data from the Third Nutrition and Health Examination Survey (NHANES III) and the NHANES III Linked Mortality File in the United States. We analyzed mortality data for 5902 participants aged 40 years and older with no history of diabetes and who had available serum C-peptide levels from the baseline examination. We grouped the participants by C-peptide quartile, and we performed Cox proportional hazards regression analysis. The primary outcome was all-cause, cardiovascular-related and coronary artery disease- related mortality. Results: The mean serum C-peptide level in the study sample was 0.78 (± standard deviation 0.47) nmol/L. The adjusted hazards ratio comparing the highest quartile with the lowest quartile was 1.80 (95% confidence interval [CI] 1.33-2.43) for all-cause mortality, 3.20 (95% CI 2.07-4.93) for cardiovascular-related mortality, and 2.73 (95% CI 1.55-4.82) for coronary artery disease-related mortality. Higher C-peptide levels were associated with increased mortality among strata of glycated hemoglobin and fasting serum glucose. Interpretation: We found an association be - tween serum C-peptide levels and all-cause and cause-specific mortality among adults without diabetes at baseline. Our finding suggests that elevated C-peptide levels may be a predictor of death. [ABSTRACT FROM AUTHOR]

Pancreas transplantation has an identity crisis and is at a crossroads. Although outcomes continue to improve in each successive era, the number of pancreas transplants performed annually in the United States has been static for several years in spite of increasing numbers of deceased donors. For most practitioners who manage diabetes, pancreas transplantation is considered an extreme measure to control diabetes. With expanded recipient selection (primarily simultaneous pancreas-kidney transplantation) in patients who are older, have a higher BMI, are minorities, or who have a type 2 diabetes phenotype, the controversy regarding type of diabetes detracts from the success of intervention. The absence of a clear and precise definition of pancreas graft failure, particularly one that lacks a measure of glycemic control, inhibits wider application of pancreas transplantation with respect to reporting long-term outcomes, comparing this treatment to alternative therapies, developing listing and allocation policy, and having a better understanding of the patient perspective. It has been suggested that the definition of pancreas graft failure should differ depending on the type of pretransplant diabetes. In this commentary, we discuss current challenges regarding the development of a uniform definition of pancreas graft failure and propose a potential solution to this vexing problem., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: The goal of the VA Diabetes Trial (VADT) was to determine the effect of intensive glucose control on macrovascular events in subjects with difficult-to-control diabetes. No significant benefit was found. This report examines predictors of the effect of intensive therapy on the primary outcome in this population.Methods: This trial included 1791 subjects. Baseline cardiovascular risk factors were collected by interview and the VA record. The analyses were done by intention to treat.Findings: Univariate analysis at baseline of predictors of a primary cardiovascular (CV) event included a prior CV event, age, insulin use at baseline, and duration of diagnosed diabetes (all P < .0001). Multivariable modeling revealed a U-shaped relationship between duration of diabetes and treatment. Modeled estimates for the hazard ratios (HRs) for treatment show that subjects with a short duration (3 years or less) of diagnosed diabetes have a nonsignificant increase in risk (HR > 1.0) after which the HR is below 1.0. From 7 to 15 years' duration at entry, subjects have HRs favoring intensive treatment. Thereafter the HR approaches 1.0 and over-21-years' duration approaches 2.0. Duration over 21 years resulted in a HR of 1.977 (CI 1.77-3.320, P < .01). Baseline c-peptide levels progressively declined up to 15 years and were stable subsequently.Interpretation: In difficult-to-control older subjects with type 2 DM, duration of diabetes altered the response to intensive glucose control. Intensive therapy may reduce CV events in subjects with a duration of 15 years or less and may increase risks in those with longer duration. [ABSTRACT FROM AUTHOR]

Aspirin use decreases colon cancer risk, but this association may vary among population subgroups. The aspirin-colon cancer association was evaluated according to body mass index and physical activity in 1,701 incident colon cancer cases diagnosed during follow-up of 139,310 participants for up to 26 years in 2 US prospective cohort studies that began in 1980 and 1992, respectively. Whether plasma C-peptide levels modified the association was examined by using a nested case-control design (n = 384 cases, 749 controls). Multiplicative and additive interactions were tested. Body mass index did not modify the association; pooled multivariable relative risks for regular aspirin use versus nonuse ranged from 0.74 to 0.75 in the normal weight and obese groups (test for multiplicative interaction, P = 0.75; test for additive interaction, P = 0.66). Pooled multivariable relative risks for regular aspirin use were 0.86 (95% confidence interval (CI): 0.66, 1.11) in the low and 0.67 (95% CI: 0.58, 0.77) in the high physical activity groups with no interaction evident on either the multiplicative or additive scale (P > 0.10). Plasma C-peptide levels also did not modify the aspirin-colon cancer association, with multivariable relative risks of 0.74 (95% CI: 0.50, 1.10) for the low and 0.65 (95% CI: 0.46, 0.92) for the high group. Reductions in colon cancer risk associated with aspirin use were not significantly modified by body mass index, physical activity, or plasma C-peptide level in this study. [ABSTRACT FROM AUTHOR]

Presents information on the topics on immunity and type 1 diabetes which are discussed during the 61st Scientific Sessions of the American Diabetes Association in Philadelphia, Pennsylvania in June 2001. Role of C-peptide deficiency in diabetes; Utilization of C-peptide in the treatment and management of type 1 diabetes; Updates on islet transplantation.

Background: Leading a Western lifestyle, being overweight, and being sedentary are associated with an increased risk of colorectal cancer. Recent theories propose that the effects of these risk factors may be mediated by increases in circulating insulin levels and in the bioactivity of insulin-like growth factor (IGF)-I. To test this hypothesis, we conducted a case-control study nested within a cohort of 14 275 women in New York.Methods: We used blood samples that had been obtained from these women from March 1985 through June 1991 and stored in a biorepository. C-peptide (a marker for insulin secretion), IGF-I, and IGF-binding proteins (IGFBPs)-1, -2, and -3 were assayed in the serum of 102 women who subsequently developed colorectal cancer and 200 matched control subjects. Logistic regression was used to relate cancer risk to these peptide levels, by adjustment for other risk factors. All statistical tests used are two-sided.Results: Colorectal cancer risk increased with increasing levels of C-peptide (P:(trend) =.001), up to an odds ratio (OR) of 2. 92 (95% confidence interval [CI] = 1.26-6.75) for the highest versus the lowest quintiles, after adjustment for smoking. For colon cancer alone (75 case subjects and 146 control subjects), ORs increased up to 3.96 (95% CI = 1.49-10.50; P:(trend) <.001) for the highest versus the lowest quintiles. A statistically significant decrease in colorectal cancer risk was observed for increasing levels of IGFBP-1 (P:(trend) =.02; OR in the upper quintile = 0.48 [95% CI = 0.23-1. 00]), as well as for the highest quintile of IGFBP-2 levels (P:(trend) =.06; OR = 0.38 [95% CI = 0.15-0.94]). Colorectal cancer risk showed a modest but statistically nonsignificant positive association with levels of IGF-I and was statistically significantly increased for the highest quintile of IGFBP-3 (OR = 2.46 [95% CI = 1. 09-5.57]).Conclusions: Chronically high levels of circulating insulin and IGFs associated with a Western lifestyle may increase colorectal cancer risk, possibly by decreasing IGFBP-1 and increasing the bioactivity of IGF-I. [ABSTRACT FROM AUTHOR]

Focuses on the clinical and biochemical phenotyping criteria for type 2 diabetes in end-stage renal disease (ESRD) patients in Ohio. Role of C-peptide concentrations in insulin synthesis; Elevation of C-peptide levels in type 1 ESRD patients; Identification of chromosomal loci.

The author comments on a study by D. H. Lee and colleagues on the link between mushroom intake and risk of cardiovascular disease and type 2 diabetes. He discusses the failure of the study to elaborate on any associations of mushrooms with other food, factors that might help reduce or control confounding, and the difficulty of estimating the power of a food-disease relationship when the underlying literature is sparse.

Diabetes mellitus (DM) is a complex metabolic disease affecting one-third of the United States population. It is characterized by hyperglycemia, where the hormone insulin is either not produced sufficiently or where there is a resistance to insulin. Patients with Type 1 DM (T1DM), in which the insulin-producing beta cells are destroyed by autoimmune mechanisms, have a significantly increased risk of developing life-threatening cardiovascular complications, even when exogenous insulin is administered. In fact, due to various factors such as limited blood glucose measurements and timing of insulin administration, only 37% of T1DM adults achieve normoglycemia. Furthermore, T1DM patients do not produce C-peptide, a cleavage product from insulin processing. C-peptide has potential therapeutic effects in vitro and in vivo on many complications of T1DM, such as peripheral neuropathy, atherosclerosis, and inflammation. Thus, delivery of C-peptide in conjunction with insulin through a pump, pancreatic islet transplantation, or genetically engineered Sertoli cells (an immune privileged cell type) may ameliorate many of the cardiovascular and vascular complications afflicting T1DM patients. [ABSTRACT FROM AUTHOR]

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Cardiovascular disease (CVD) is the leading cause of death among individuals with diabetes, but little is known about the role of exposures to environmental chemicals such as pesticides in the early development of CVD risk in this population. To describe changes over time in concentrations of pesticide biomarkers among youth with diabetes in the United States and to estimate the longitudinal association between these concentrations and established risk factors for CVD. Pesticide biomarkers were quantified in urine and serum samples from 87 youth with diabetes participating in the multi-center SEARCH cohort study. Samples were obtained around the time of diagnosis (baseline visit, between 2006 and 2010) and, on average, 5.4 years later (follow-up visit, between 2012 and 2015). We calculated geometric mean (95% CI) pesticide biomarker concentrations. Eight CVD risk factors were measured at these two time points: body mass index (BMI) z-score, HbA1c, insulin sensitivity, fasting C-peptide (FCP), LDL cholesterol, HDL cholesterol, total cholesterol, and triglycerides. Linear regression models were used to estimate the associations between each pesticide biomarker at baseline and each CVD risk factor at follow-up, adjusting for baseline health outcome, elapsed time between baseline and follow up, sex, age, race/ethnicity, and diabetes type. Participants were, on average, 14.2 years old at their baseline visit, and most were diagnosed with type 1 diabetes (57.5%). 4-nitrophenol, 3-phenoxybenzoic acid, 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol, 2,2-bis(4-chlorophenyl)-1,1-dichloroethene, and hexachlorobenzene were detected in a majority of participants at both time points. Participants in the highest quartile of 2,4-D and 4-nitrophenol at baseline had HbA1c levels at follow-up that were 1.05 percentage points (95% CI: −0.40, 2.51) and 1.27 percentage points (0.22, 2.75) higher, respectively, than participants in the lowest quartile of these pesticide biomarkers at baseline. These participants also had lower log FCP levels (indicating reduced beta-cell function) compared to participants in the lowest quartile at baseline: beta (95% CI) for log FCP of −0.64 (−1.17, −0.11) for 2,4-D and −0.39 (−0.96, 0.18) for 4-nitrophenol. In other words, participants in the highest quartile of 2,4-D had a 47.3% lower FCP level compared to participants in the lowest quartile, and those in the highest quartile of 4-nitrophenol had a 32.3% lower FCP level than those in the lowest quartile. Participants with trans-nonachlor concentrations in the highest quartile at baseline had HbA1c levels that were 1.45 percentage points (−0.11, 3.01) higher and log FCP levels that were −0.28 (−0.84, 0.28) lower than participants in the lowest quartile at baseline, that is to say, participants in the highest quartile of trans-nonachlor had a 24.4% lower FCP level than those in the lowest quartile. While not all of these results were statistically significant, potentially due to the small same size, clinically, there appears to be quantitative differences. No associations were observed between any pesticide biomarker at baseline with BMI z-score or insulin sensitivity at follow-up. Exposure to select pesticides may be associated with impaired beta-cell function and poorer glycemic control among youth with diabetes. • Prospective associations of pesticides with clinical outcomes in youth with diabetes. • 2,4-D and 4-nitrophenol were associated with poorer glycemic control. • 2,4-D and 4-nitrophenol were associated with impaired beta-cell function. • Trans-nonachlor was associated with poorer glycemic control. • Trans-nonachlor was associated with impaired beta-cell function. [ABSTRACT FROM AUTHOR]

Background: The empirical dietary index for hyperinsulinemia (EDIH) score is a validated food-based dietary score that assesses the ability of whole-food diets to predict plasma c-peptide concentrations. Although the EDIH has been extensively applied and found to be predictive of risk of developing major chronic diseases, its influence on cancer survival has not been evaluated. We applied the EDIH score in a large cohort of colorectal cancer patients to assess the insulinemic potential of their dietary patterns after diagnosis and determine its influence on survival outcomes., Methods: We calculated EDIH scores to assess the insulinemic potential of post-diagnosis dietary patterns and examined survival outcomes in a sample of 1718 stage I-III colorectal cancer patients in the Nurses' Health Study and Health Professionals Follow-up Study cohorts. Multivariable-adjusted Cox regression was applied to compute hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer-specific mortality and all-cause mortality. We also examined the influence of change in diet from pre- to post-diagnosis period, on mortality., Results: During a median follow-up of 9.9 years, there were 1008 deaths, which included 272 colorectal cancer-specific deaths (27%). In the multivariable-adjusted analyses, colorectal cancer patients in the highest compared to lowest EDIH quintile, had a 66% greater risk of dying from colorectal cancer: HR, 1.66; 95% CI, 1.03, 2.69; and a 24% greater risk of all-cause death: HR, 1.24; 95%CI, 0.97, 1.58. Compared to patients who consumed low insulinemic diets from pre- to post-diagnosis period, patients who persistently consumed hyperinsulinemic diets were at higher risk of colorectal cancer death (HR,1.51; 95%CI, 0.98, 2.32) and all-cause death (HR, 1.31; 95%CI, 1.04, 2.64)., Conclusion: Our findings suggest that a hyperinsulinemic dietary pattern after diagnosis of colorectal cancer is associated with poorer survival. Interventions with dietary patterns to reduce insulinemic activity and impact survivorship are warranted.

BACKGROUND Clinical criteria and the presence of auto-antibodies might not be sufficient to discriminate type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in children with new onset of disease. OBJECTIVE To determine whether biochemical markers can be used to distinguish T1DM from T2DM. DESIGN AND INTERVENTION This was a single-center, US-based, prospective study of children with newly diagnosed primary diabetes. Children with secondary diabetes as a result of medication, cystic fibrosis, or other medical conditions were excluded. Eligible participants were enrolled between July 1999 and July 2000. T1DM was presumptively diagnosed in nonobese children who were dependent on insulin to maintain glycemic control. T2DM was presumptively diagnosed in children with a BMI >85% for age and sex and a family history of T2DM, who were insulin-independent and glutamic acid decarboxylase autoantibody-negative. Glucose, CO2, urinary ketones, and HbA1c levels were measured at diagnosis. A fasting blood sample was collected on the morning of diagnosis or on the morning after diagnosis to determine the levels of C-peptide and insulin-like-growth-factor-binding protein 1 (IGFBP-1). C-peptide was assessed by immuno-chemiluminescent assay and IGFBP-1 was assessed by radioimmunoassay. OUTCOME MEASURES The main outcome measures were the receiver operator characteristic (ROC), area under the curve (AUC), sensitivity, specificity, and cut-off value of each biochemical marker. RESULTS The study enrolled a total of 175 children, 149 of whom were presumptively diagnosed with T1DM. The mean age of children with T1DM was 8.7 years, compared with a mean age of 14.2 years for children with T2DM (P<0.001). Children with T1DM were most likely be non- Hispanic whites (78%, P<0.001). By contrast, children with T2DM were most likely to be non- Hispanic blacks (58%, P<0.001). Markers of insulin resistance demonstrated a significant difference between T1DM and T2DM. The mean fasting C-peptide level was 0.13 nmol/l in T1DM and 0.88nmol/l in T2DM (P<0.001). The ROC curve for fasting C-peptide determined a cut-off value of 0.28nmol/l, with a sensitivity of 83%, a specificity of 89%, and an AUC of 0.94. The mean fasting IGFBP-1 level was 38.1 ng/ml in T1DM and 3.6ng/ml in T2DM (P<0.001). The ROC curve for fasting IGFBP-1 determined a cut-off value of 3.6ng/ml, with a sensitivity of 93%, a specificity of 79%, and an AUC of 0.92. The CO2 level for children with TIDM was 17.9mmol/l, versus 22.7mmol/l for children with T2DM (P= 0.016). The ROC curve for CO2 determined a cut-off value of 21.5 mmol/l, with a sensitivity of 83%, a specificity of 64%, and an AUC of 0.76. Urinary ketones were present in 79% and 56% of children with T1DM and T2DM, respectively. A cut-off value of 10 mg/dl was associated with a sensitivity of 74%, a specificity of 52%, and an AUC of 0.73. CONCLUSION Children with new-onset T1DM and T2DM can be distinguished by a combination of biochemical markers. [ABSTRACT FROM AUTHOR]