Objective: To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at nearnormal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy.Methods: Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome.Results: After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conven-tional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; PϽ.001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (PϽ.001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT. Conclusion:The persistent difference in diabetic retinopathy between former intensive and conventional therapy ("metabolic memory") continues for at least 10 years but may be waning.

Scope Dietary prebiotics show potential in anti-diabetes. Dietary resistant starch (RS) has a favorable impact on gut hormone profiles, including glucagon-like peptide-1 (GLP-1) consistently released, a potent anti-diabetic incretin. Also RS reduced body fat and improved glucose tolerance in rats and mice. In the current project, we hypothesize that dietary-resistant starch can improve insulin sensitivity and pancreatic β cell mass in a type 2 diabetic rat model. Altered gut fermentation and microbiota are the initial mechanisms, and enhancement in serum GLP-1 is the secondary mechanism. Methods and results In this study, GK rats were fed an RS diet with 30% RS and an energy control diet. After 10 wk, these rats were mated and went through pregnancy and lactation. At the end of the study, pancreatic β cell mass, insulin sensitivity, pancreatic insulin content, total GLP-1 levels, cecal short-chain fatty acid concentrations and butyrate producing bacteria in cecal contents were greatly improved by RS feeding. The offspring of RS-fed dams showed improved fasting glucose levels and normal growth curves. Conclusion Dietary RS is potentially of great therapeutic importance in the treatment of diabetes and improvement in outcomes of pregnancy complicated by diabetes.

Eighteen Holstein (experiment 1) and 15 Jersey (experiment 2) heifer calves were fed milk replacer once or twice daily to determine effects of feeding frequency on weight gain, starter intake, and glucose metabolism. Body weights were measured weekly from birth to 8 wk. Blood samples were collected at wk 1 through 6 from all calves before and at 30, 60, 90, 120 and 180 min after the morning feeding. Plasma was analyzed for glucose, insulin, glucagon, and nonesterified fatty acids (NEFA). Urine was collected 90 min postfeeding to measure glucose concentration. Treatment did not affect mean starter intake or body weight. In experiments 1 and 2 mean plasma glucagon, glucose, NEFA, and insulin and urinary glucose concentrations were not affected by treatment. There was an interaction of sampling time and treatment for plasma insulin concentrations but not for glucose concentrations in both experiments. Following feeding, calves fed milk replacer once daily had higher insulin concentrations than those fed twice daily. There was an interaction of sampling time and treatment for plasma NEFA concentrations in Jersey calves only. Jersey calves fed milk replacer once daily had higher plasma NEFA concentrations before the morning milk replacer feeding. At wk 3 and 6, frequently sampled intravenous glucose tolerance tests were performed to assess glucose effectiveness, insulin sensitivity, and acute insulin response. In experiments 1 and 2 glucose effectiveness and insulin sensitivity were similar regardless of milk replacer feeding frequency. In Holstein and Jersey calves fed milk replacer twice daily, acute insulin response was greater than in calves fed once daily. However, insulin sensitivity decreased with age, while acute insulin response increased with age. These data suggest that feeding calves milk replacer once daily did not deleteriously affect performance or glucose metabolism regardless of breed.

Objective: Obesity is a health concern. Resistant starch (RS) type 2 from high-amylose maize (HAM-RS2) and dietary sodium butyrate (SB) reduce abdominal fat in rodents. RS treatment is associated with increased gut hormones peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), but it is not known if SB increases these hormones. Design and Methods: This was investigated in a 2 3 2 rat study with HAM-RS2 (0 or 28% weight) and dietary sodium butyrate (0 and 3.2%) resulting in isocaloric treatments: energy control (EC), sodium butyrate (SB), HAM-RS2 (RS), and the combination (SBRS). Results: RS and SB reduced abdominal fat and the combination reduced abdominal fat compared to SB and RS. RS was associated with increased fermentation in the cecum. Serum PYY and GLP-1 total were increased with RS treatment. RS treatment was associated with increased cecal butyrate produced from fermentation of RS, but there was no cecal increase for dietary SB. Conclusions: SB after its absorption into the blood appears to not affect production of PYY and GLP-1, while butyrate from fermentation in the cecum promotes increased PYY and GLP-1. Future studies with lower doses of RS and SB are warranted and the combination may be beneficial for human health.

Background: Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath's four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. Results: Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18-20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = − 1.99, p = 0.045) and leisure time (β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. Conclusions: Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.