Glycaemic control and risk of incident urinary incontinence in women with Type 1 diabetes: results from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study

AimsTo study the impact of glycaemic control on urinary incontinence in women who participated in the Diabetes Control and Complications Trial (DCCT; 1983–1993) and its observational follow‐up study, the Epidemiology of Diabetes Interventions and Complications (EDIC; 1994–present).MethodsStudy participants were women who completed, at both years 10 (2003) and 17 (2010) of the EDIC follow‐up, the urological assessment questionnaire (UroEDIC). Urinary incontinence was defined as self‐reported involuntary leakage of urine that occurred at least weekly. Incident urinary incontinence was defined as weekly urinary incontinence present at EDIC year 17 but not at EDIC year 10. Multivariable regression models were used to examine the association of incident urinary incontinence with comorbid prevalent conditions and glycaemic control (mean HbA1c over the first 10 years of EDIC).ResultsA total of 64 (15.3%) women with Type 1 diabetes (mean age 43.6 ± 6.3 years at EDIC year 10) reported incident urinary incontinence at EDIC year 17. When adjusted for clinical covariates (including age, DCCT cohort assignment, DCCT treatment arm, BMI, insulin dosage, parity, hysterectomy, autonomic neuropathy and urinary tract infection in the last year), the mean EDIC HbA1c was associated with increased odds of incident urinary incontinence (odds ratio 1.03, 95% CI 1.01–1.06 per mmol/mol increase; odds ratio 1.41, 95% CI 1.07–1.89 per % HbA1c increase).ConclusionsIncident urinary incontinence was associated with higher HbA1c levels in women with Type 1 diabetes, independent of other recognized risk factors. These results suggest the potential for women to modify their risk of urinary incontinence with improved glycaemic control. (Clinical Trials Registry no: NCT00360815 and NCT00360893).What’s new?Research to date has failed to show an association between glycaemic control and urinary incontinence (UI) in women with diabetes.We examined the relationship between HbA1c and UI using longitudinal data from the Diabetes Control and Complications Trial (DCCT) and its observational follow‐up, the Epidemiology of Diabetes Interventions and Complications (EDIC) study.Our findings show that the odds of UI increase with poor glycaemic control in women with Type 1 diabetes, independently of other well‐described predictors of UI.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134490/1/dme13126.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134490/2/dme13126_am.pd

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Cardiovascular risk factor progression in adolescents and young adults with youth-onset type 2 diabetes

AIMS: Youth-onset type 2 diabetes (T2D) confers a high risk of early adverse cardiovascular morbidity. We describe the cumulative incidence and prevalence of cardiovascular risk factors over time and examine relationships with diabetes progression in young adults with youth-onset T2D from the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. METHODS: Longitudinal data was used to evaluate the relationships between hypertension, LDL-C dyslipidemia, hypertriglyceridemia, and smoking with risk factors in 677 participants. RESULTS: Baseline mean age was 14 ± 2 years and mean follow-up 10.2 ± 4.5 years. The 14-year cumulative incidence of hypertension, LDL-C dyslipidemia, and hypertriglyceridemia was 59%, 33%, and 37% respectively. Average prevalence of reported smoking was 23%. Male sex, non-Hispanic white race/ethnicity, obesity, poor glycemic control, lower insulin sensitivity, and reduced beta-cell function were significantly associated with an unfavorable risk profile. At end of follow-up, 54% had ≥2 cardiovascular risk factors in addition to T2D. CONCLUSIONS: Cardiovascular risk factor incidence and prevalence was high over a decade of follow-up in young adults with youth-onset T2D. Glucose control and management of cardiovascular risk factors is critical in youth with T2D for prevention of cardiovascular morbidity and mortality

Effect of glycemic treatment and microvascular complications on menopause inwomen with type 1 diabetes in the diabetes control and complications trial/ epidemiology of diabetes interventions and complications (DCCT/EDIC) cohort

OBJECTIVE We examined the impact of intensive versus conventional diabetes treatment uponmenopause among women with type 1 diabetes in the Diabetes Control and Complications Trial (DCCT), a randomized controlled trial of intensive diabetes treatment, and its observational follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. RESEARCH DESIGN AND METHODS In a secondary analysis of women in the DCCT/EDIC (n = 657), outcomes were the cumulative incidences of natural menopause and surgical menopause. Cox regression analyses were used to examine associations with treatment group, time-varying estimates of hemoglobin A1c (HbA1c), insulin dosage, BMI, and microvascular complications (retinopathy, nephropathy, and neuropathy). RESULTS By EDIC year 18, after an average of 28 years of follow-up, 240 (38%) women had experienced natural menopause and 115 (18%) women had experienced surgical menopause. Age at natural menopause was similar in the intensive versus conventional groups (49.9 vs. 49.0 years; P = 0.28), and age at surgicalmenopause was similar in the intensive versus conventional groups (40.8 vs. 42.0 years; P = 0.31). In multivariable models, treatment group, HbA1c, and microvascular complications were not associated with risk of natural or surgical menopause. Each 10 unit/day increase in insulin dosage decreased risk of natural menopause (hazard ratio [HR] 0.91, 95% CI 0.75-0.98) and each kg/m2 increase in BMI increased risk of surgical menopause (HR 1.08, 95% CI 1.00-1.16). CONCLUSIONS In the DCCT/EDIC, intensive versus conventional treatment group and HbA1c level were not associated with menopause risk. Greater insulin dose was associated with lower menopause risk. © 2014 by the American Diabetes Association

Chronic Kidney Disease Associates with Cognitive Decline in Middle-aged and Older Adults with Long-standing Type 1 Diabetes

BACKGROUND: Individuals with chronic kidney disease (CKD) or type 1 diabetes (T1D) are at risk for cognitive decline, but it is unclear if these associations are with albuminuria, estimated glomerular filtration rate (eGFR), or both. METHODS: We examined the longitudinal relationships between CKD and change in cognition in 1,051 participants with T1D in the Diabetes Control and Complications Trial (DCCT) and its follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. Albumin excretion rate (AER) and eGFR were measured every 1-2 years. Three cognitive domains were assessed repeatedly over a 32-year period: immediate memory; delayed memory; and psychomotor and mental efficiency. Associations between cognitive function and CKD were assessed 1) longitudinally, and 2) in models utilizing eGFR and albuminuria measurements over the first 15-20 years with subsequent change in cognitive function over the ensuing 14 years(when decline in cognition was greatest).. RESULTS: In fully-adjusted longitudinal analyses, the magnitude of decline in the psychomotor and mental efficiency domain score was associated with eGFR \u3c60 mL/min/1.73m2 (β -0.449, 95%CI [-0.640, -0.259]) and sustained AER 30-\u3c300 mg/24hr (β -0.148, 95%CI [-0.270, -0.026]). This was equivalent to a decrease associated with approximately 11 and 4 years of ageing, respectively. In analyses focused on changes in cognition between study years 18 and 32, eGFR \u3c60 mL/min/1.73m2 was associated with reduced psychomotor and mental efficiency (β -0.915, 95%CI [-1.613, -0.217]). CONCLUSIONS: In T1D, development of CKD was associated with a subsequent reduction on cognitive tasks requiring psychomotor and mental efficiency. These data highlight the need for increased recognition of risk factors for neurologic sequelae in patients with T1D, as well as preventive and treatment strategies to ameliorate cognitive decline

Ovarian reserve in women with Type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study.

Markers of ovarian reserve such as anti-Müllerian hormone (AMH) are used in the management of fertility and prediction of menopause. Although women with type 1 diabetes have a high prevalence of reproductive disorders, no studies have examined whether markers of ovarian reserve are associated with randomization to intensive insulin therapy and subsequent markers of glycemic control. Using data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study, we found that the strongest predictor of AMH was chronologic age, and that diabetes-specific variables such as randomization to intensive therapy, insulin dose, and glycemic control were not associated with AMH concentrations

Effect of Glycemic Treatment and Microvascular Complications on Menopause in Women With Type 1 Diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Cohort

OBJECTIVE We examined the impact of intensive versus conventional diabetes treatment upon menopause among women with type 1 diabetes in the Diabetes Control and Complications Trial (DCCT), a randomized controlled trial of intensive diabetes treatment, and its observational follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. RESEARCH DESIGN AND METHODS In a secondary analysis of women in the DCCT/EDIC (n = 657), outcomes were the cumulative incidences of natural menopause and surgical menopause. Cox regression analyses were used to examine associations with treatment group, time-varying estimates of hemoglobin A1c (HbA1c), insulin dosage, BMI, and microvascular complications (retinopathy, nephropathy, and neuropathy). RESULTS By EDIC year 18, after an average of 28 years of follow-up, 240 (38%) women had experienced natural menopause and 115 (18%) women had experienced surgical menopause. Age at natural menopause was similar in the intensive versus conventional groups (49.9 vs. 49.0 years; P = 0.28), and age at surgical menopause was similar in the intensive versus conventional groups (40.8 vs. 42.0 years; P = 0.31). In multivariable models, treatment group, HbA1c, and microvascular complications were not associated with risk of natural or surgical menopause. Each 10 unit/day increase in insulin dosage decreased risk of natural menopause (hazard ratio [HR] 0.91, 95% CI 0.75–0.98) and each kg/m2 increase in BMI increased risk of surgical menopause (HR 1.08, 95% CI 1.00–1.16). CONCLUSIONS In the DCCT/EDIC, intensive versus conventional treatment group and HbA1c level were not associated with menopause risk. Greater insulin dose was associated with lower menopause risk