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1. Glycemic Control and Urinary Tract Infections in Women with Type 1 Diabetes: Results from the DCCT/EDIC

Author

Lenherr, Sara M, Clemens, J Quentin, Braffett, Barbara H, Cleary, Patricia A, Dunn, Rodney L, Hotaling, James M, Jacobson, Alan M, Kim, Catherine, Herman, William, Brown, Jeanette S, Wessells, Hunter, Sarma, Aruna V, Nathan, DM, Zinman, B, Crofford, O, Genuth, S, Brown-Friday, J, Crandall, J, Engel, H, Engel, S, Martinez, H, Phillips, M, Reid, M, Shamoon, H, Sheindlin, J, Gubitosi-Klug, R, Mayer, L, Pendegast, S, Zegarra, H, Miller, D, Singerman, L, Smith-Brewer, S, Novak, M, Quin, J, Genuth, Saul, Palmert, M, Brown, E, McConnell, J, Pugsley, P, Crawford, P, Dahms, W, Brillon, D, Lackaye, ME, Kiss, S, Chan, R, Orlin, A, Rubin, M, Reppucci, V, Lee, T, Heinemann, M, Chang, S, Levy, B, Jovanovic, L, Richardson, M, Bosco, B, Dwoskin, A, Hanna, R, Barron, S, Campbell, R, Bhan, A, Kruger, D, Jones, JK, Edwards, PA, Carey, JD, Angus, E, Thomas, A, Galprin, A, McLellan, M, Whitehouse, F, Bergenstal, R, Johnson, M, Gunyou, K, Thomas, L, Laechelt, J, Hollander, P, Spencer, M, Kendall, D, Cuddihy, R, Callahan, P, List, S, Gott, J, Rude, N, Olson, B, Franz, M, Castle, G, Birk, R, Nelson, J, Freking, D, Gill, L, Mestrezat, W, Etzwiler, D, Morgan, K, Aiello, LP, Golden, E, Arrigg, P, Asuquo, V, Beaser, R, Bestourous, L, and Cavallerano, J

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Infectious Diseases, Clinical Research, Urologic Diseases, Diabetes, Prevention, Reproductive health and childbirth, Renal and urogenital, Infection, Metabolic and endocrine, Adolescent, Adult, Blood Glucose, Body Mass Index, Diabetes Mellitus, Type 1, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Risk Factors, Surveys and Questionnaires, Urinary Incontinence, Urinary Tract Infections, Young Adult, DCCT/EDIC Research Group, diabetes mellitus, risk factors, urinary tract infections, Clinical Sciences, Urology & Nephrology, Clinical sciences
Abstract

PurposeWe examined the relationship between glycemic control and urinary tract infections in women with type 1 diabetes mellitus.Materials and methodsWomen enrolled in the Epidemiology of Diabetes Interventions and Complications study, the observational followup of the Diabetes Control and Complications Trial, were surveyed to assess the rate of physician diagnosed urinary tract infections in the preceding 12 months. The relationship between glycated hemoglobin levels and number of urinary tract infections in the previous 12 months was assessed using a multivariable Poisson regression model.ResultsA total of 572 women were evaluated at year 17. Mean age was 50.7 ± 7.2 years, mean body mass index was 28.6 ± 5.9 kg/m(2), mean type 1 diabetes duration was 29.8 ± 5.0 years and mean glycated hemoglobin was 8.0% ± 0.9%. Of these women 86 (15.0%) reported at least 1 physician diagnosed urinary tract infection during the last 12 months. Higher glycated hemoglobin levels were significantly associated with number of urinary tract infections such that for every unit increase (1%) in recent glycated hemoglobin level, there was a 21% (p=0.02) increase in urinary tract infection frequency in the previous 12 months after adjusting for race, hysterectomy status, urinary incontinence, sexual activity in the last 12 months, peripheral and autonomic neuropathy, and nephropathy.ConclusionsThe frequency of urinary tract infections increases with poor glycemic control in women with type 1 diabetes. This relationship is independent of other well described predictors of urinary tract infections and suggests that factors directly related to glycemic control may influence the risk of lower urinary tract infections.

Published
2016

2. Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort

Author

Chen, Zhuo, Miao, Feng, Paterson, Andrew D, Lachin, John M, Zhang, Lingxiao, Schones, Dustin E, Wu, Xiwei, Wang, Jinhui, Tompkins, Joshua D, Genuth, Saul, Braffett, Barbara H, Riggs, Arthur D, Natarajan, Rama, Nathan, DM, Zinman, B, Crofford, O, Genuth, S, Brown-Friday, J, Crandall, J, Engel, H, Engel, S, Martinez, H, Phillips, M, Reid, M, Shamoon, H, Sheindlin, J, Gubitosi-Klug, R, Mayer, L, Pendegast, S, Zegarra, H, Miller, D, Singerman, L, Smith-Brewer, S, Novak, M, Quin, J, Palmert, M, Brown, E, McConnell, J, Pugsley, P, Crawford, P, Dahms, W, Brillon, D, Lackaye, ME, Kiss, S, Chan, R, Orlin, A, Rubin, M, Reppucci, V, Lee, T, Heinemann, M, Chang, S, Levy, B, Jovanovic, L, Richardson, M, Bosco, B, Dwoskin, A, Hanna, R, Barron, S, Campbell, R, Bhan, A, Kruger, D, Jones, JK, Edwards, PA, Carey, JD, Angus, E, Thomas, A, Galprin, A, McLellan, M, Whitehouse, F, Bergenstal, R, Johnson, M, Gunyou, K, Thomas, L, Laechelt, J, Hollander, P, Spencer, M, Kendall, D, Cuddihy, R, Callahan, P, List, S, Gott, J, Rude, N, Olson, B, Franz, M, Castle, G, Birk, R, Nelson, J, Freking, D, Gill, L, Mestrezat, W, Etzwiler, D, Morgan, K, Aiello, LP, Golden, E, Arrigg, P, Asuquo, V, Beaser, R, and Bestourous, L

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Research, Diabetes, Human Genome, Nutrition, Autoimmune Disease, Prevention, 2.1 Biological and endogenous factors, Metabolic and endocrine, Adolescent, Adult, Carrier Proteins, Cell Line, Tumor, Cohort Studies, DNA Methylation, Diabetes Mellitus, Type 1, Epigenomics, Female, Genetic Loci, Glycated Hemoglobin, Humans, Male, DCCT/EDIC Research Group, DNA methylation, TXNIP, diabetic complications, epigenetics, metabolic memory
Abstract

We examined whether persistence of epigenetic DNA methylation (DNA-me) alterations at specific loci over two different time points in people with diabetes are associated with metabolic memory, the prolonged beneficial effects of intensive vs. conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We compared DNA-me profiles in genomic DNA of whole blood (WB) isolated at EDIC Study baseline from 32 cases (DCCT conventional therapy group subjects showing retinopathy or albuminuria progression by EDIC Study year 10) vs. 31 controls (DCCT intensive therapy group subjects without complication progression by EDIC year 10). DNA-me was also profiled in blood monocytes (Monos) of the same patients obtained during EDIC Study years 16-17. In WB, 153 loci depicted hypomethylation, and 225 depicted hypermethylation, whereas in Monos, 155 hypomethylated loci and 247 hypermethylated loci were found (fold change ≥1.3; P < 0.005; cases vs. controls). Twelve annotated differentially methylated loci were common in both WB and Monos, including thioredoxin-interacting protein (TXNIP), known to be associated with hyperglycemia and related complications. A set of differentially methylated loci depicted similar trends of associations with prior HbA1c in both WB and Monos. In vitro, high glucose induced similar persistent hypomethylation at TXNIP in cultured THP1 Monos. These results show that DNA-me differences during the DCCT persist at certain loci associated with glycemia for several years during the EDIC Study and support an epigenetic explanation for metabolic memory.

Published
2016

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