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.

We found that there was a profound effect of non-dipping upon the rate of decline of renal function in patients with diabetic nephropathy.

Measurement of bone density and turnover was assessed in 20 premenopausal females with Type 1 diabetes mellitus and 27 age-sex-matched controls. Measurement was made of spinal (L2-4) and neck of femur bone density by dual-energy X-ray absorptiometry. L2-4 density was significantly higher in the diabetic patients compared with controls (1.224 +/- 0.021 g cm-2 vs. 1.161 +/- 0.020 g cm-2: p = 0.016). No significant difference was noted between the groups in neck of femur density. Measurement of bone formation was assessed by serum alkaline phosphatase and bone resorption by fasting urinary hydroxyproline/creatinine ratio. Alkaline phosphatase was significantly higher in the diabetic patients (185 +/- 16 Ul-1 vs 135 +/- 10 Ul-1: p < 0.01) as was hydroxyproline/creatinine ratio (0.028 +/- 0.003 vs 0.017 +/- 0.002: p = 0.002). No significant correlation was found between L2-4 density and glycated haemoglobin, duration of diabetes or daily dose of insulin taken. These data suggest that osteopenia is not associated with Type 1 diabetes mellitus; however these patients do have evidence of increased bone turnover and may therefore be at risk of osteoporosis in later life, particularly after the menopause.

No abstract

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.

Diabetes is an increasingly common condition and hence, managing dying patients with diabetes as a co-morbidity will become a frequent challenge. It is uncertain whether there is net beneficence in preventing hyperglycaemia in diabetic patients during the terminal phase or whether the distress involved in administering therapy and blood glucose monitoring may outweigh this ordeal. Since there is no available evidence upon which to base clinical decisions, a semi-structured questionnaire based around three clinical vignettes was sent to consultants in diabetes and palliative care in the UK. There was consensus of opinion from both groups of consultants that treatment and monitoring should be stopped in patients with type 2 diabetes, once in the terminal phase. There was less consensus regarding management of type 1 diabetes. Practical issues were raised by both groups of consultants and clinical guidelines are suggested.

Due to its high NPV, MIBI scintigraphy can usefully exclude malignancy for Thy1 and Thy2 lesions. Its low specificity means MIBI scintigraphy cannot be recommended as a first-line investigation, but as a second-line investigation MIBI scintigraphy may lead to a lower rate of unnecessary thyroidectomies. Combined FNA/MIBI strategies are potentially cost-effective in the management of solitary or dominant thyroid nodules.

1. The effects of acute hypoglycaemia on haemostasis, fibrinolysis, blood viscosity and erythrocyte aggregation were examined after acute insulin-induced hypoglycaemia in six normal male subjects and in six male patients with poorly controlled insulin-dependent diabetes. In the control subjects hypoglycaemia caused a significant increase in the concentration of von Willebrand factor, with no change in the concentrations of fibrinogen and cross-linked fibrin degradation products. Fibrinolysis was enhanced, as indicated by significant increases in tissue plasminogen activator concentration and the fibrin plate lysis area, with a fall in plasminogen-activator inhibitor activity, suggesting complex formation. Whole-blood and plasma viscosity increased significantly after hypoglycaemia, but there was no significant change in erythrocyte aggregation tendency. 2. In diabetic patients the increase in the concentration of von Willebrand factor was significantly greater than in the control group (analysis of variance, P less than 0.02). The basal concentration of tissue plasminogen activator was reduced at 3.7 +/- 0.7 mg/l (mean +/- SEM) in the diabetic group compared with 8.5 +/- 1.3 mg/l in the control group (Student's t-test, P less than 0.01), but thereafter the increase in response to hypoglycaemia was similar. The changes in the other variables were not significantly different from the changes in the control group. 3. During acute hypoglycaemia in poorly controlled diabetic patients there is promotion of haemostasis with a greater increase in the concentration of von Willebrand factor, which, in association with the increase in viscosity, might reduce perfusion in diabetic microangiopathy, leading to aggravation of the microvascular complications of diabetes.