Mid-pregnancy sleep disturbances are not associated with mid-pregnancy maternal glycemia.

Background: In pregnancy, epidemiological data have consistently shown strong associations between sleep quality and duration and maternal glycemia. However, other sleep disturbances such as difficulty falling asleep and staying asleep are common in pregnancy. They may contribute to impaired maternal glycemia through sympathetic nervous system activity, systemic inflammation, and hormonal pathways. However, there is little research examining associations between these specific sleep disturbances and maternal glycemia. Objective: This study aimed to investigate the associations of sleep disturbances during mid-pregnancy and mid-pregnancy maternal glycemia and gestational diabetes subtypes. Study Design: This is a secondary data analysis of the Comparison of Two Screening Strategies for Gestational Diabetes trial. Participants (n = 828) self-reported the frequency of sleep disturbances (i.e., trouble falling asleep, trouble staying asleep, waking several times per night, and waking feeling tired or worn out) in mid-pregnancy. Gestational diabetes was diagnosed using either the International Associations of Diabetes and Pregnancy Study Groups or Carpenter-Coustan approach. We defined gestational diabetes subtypes based on the degree of insulin resistance and beta-cell dysfunction. We used multinomial logistic regression to examine associations of sleep disturbances with gestational diabetes status (i.e., normal, mild glycemic dysfunction, and gestational diabetes) and gestational diabetes subtypes (i.e., neither insulin resistance or beta-cell dysfunction, insulin resistance only, beta-cell dysfunction only, and insulin resistance and beta-cell dysfunction). Results: A total of 665 participants (80%) had normal glycemia, 81 (10%) mild hyperglycemia, and 80 (10%) had gestational diabetes. Among participants with gestational diabetes, 62 (78%) had both insulin resistance and beta-cell dysfunction, 15 (19 %) had insulin resistance only, and 3 had beta-cell dysfunction only or neither insulin resistance nor beta-cell dysfunction. Sleep disturbance frequency was not associated with maternal glycemia or gestational diabetes subtypes. Conclusions: Sleep disturbances in mid-pregnancy were not associated with maternal glycemia during mid-pregnancy. Future research should collect data on sleep disturbances at multiple time points in pregnancy and in combination with other sleep disturbances to determine whether sleep plays any role in maternal glycemic control.

Healthy Eating Index Diet Quality in Randomized Weight Loss Trials: A Systematic Review.

BACKGROUND: Weight loss interventions focus on dietary and physical activity changes to induce weight loss. Both through weight loss and independent of it, diet quality is important for reducing chronic disease risk. However, whether and how diet quality changes over the course of a behavioral intervention is unclear. OBJECTIVE: To systematically review the evidence from randomized controlled trials on the effect of behavioral interventions on diet quality as defined by the Healthy Eating Index (HEI) among adults with overweight and obesity. METHODS: PubMed, Ebscohost CINAHL, Embase, OVID APA PsycInfo, Scopus, and Web of Science were searched through May 2021. Inclusion criteria comprised randomized controlled trial design, a primary or secondary aim of weight loss, a sample of US adults with overweight or obesity, measurement using the HEI-2005, 2010, or 2015, and assessment of the time by treatment effect. Interventions must have included behavioral components and lasted at least 3 months. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. The systematic review protocol was published on Open Science Framework. RESULTS: Of 3,707 citations retrieved, 18 studies met inclusion criteria. A wide array of behavioral interventions were assessed, including in-person and mobile health interventions as well as those prescribing intake of specific foods. Risk of bias in the included studies primarily arose from the measurement of the outcome variable. Sample sizes ranged from 34 to 413 participants. Nine studies used multiple dietary recalls, with few using the recommended method of Healthy Eating Index calculation. Changes in diet quality ranged from no improvement to a 20-point improvement. More often, improvement was in the 4- to 7-point range. CONCLUSIONS: The evidence for the efficacy of behavioral weight loss interventions for improving diet quality among adults with overweight and obesity is limited. Modest improvements in HEI scores were observed in the reviewed studies.

Predictors of the age at which natural menopause occurs in women with type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications (EDC) study.

OBJECTIVE: Women with type 1 diabetes (T1D) are thought to experience menopause earlier than women without diabetes, although not all studies agree. We assessed metabolic predictors of the age at which natural menopause occurs among women with T1D participating in the Epidemiology of Diabetes Complications study. METHODS: Women with childhood-onset (<17 y) of T1D who underwent natural menopause without use of hormone therapy during their menopausal transition were included in the analysis (n = 105; mean baseline age, 29.5 and diabetes duration, 20.2 y). Self-reported reproductive history and the Women's Ischemia Syndrome Evaluation hormonal algorithms were used to determine menopause status. Linear regression was used to ascertain whether time-weighted metabolic factors (eg, BMI, lipids, HbA1c, insulin dose, albumin excretion rate [AER]) were associated with age at natural menopause. RESULTS: Univariately, only insulin dose (ß = -4.87, P = 0.04) and log (AER) (ß = -0.62, P = 0.02) were associated (negatively) with age at natural menopause. Adjusting for BMI, smoking status, lipids, HbA1c, number of pregnancies, and oral contraceptive use, each 0.1 unit increase in the daily dose of insulin per kilogram body weight was associated with 0.64 years younger age at natural menopause (P = 0.01), while for every 30% increase in AER, age at natural menopause decreased by 0.18 years (P = 0.03). CONCLUSION: Higher average levels of insulin dose and AER over time were significantly associated with a younger age at which natural menopause occurred among women with T1D. The biologic mechanisms underlying the observed associations between exogenous insulin dose and AER on reproductive health should be investigated among women with T1D.

Women with Type 1 diabetes (T1D) experience a shorter reproductive period compared with nondiabetic women: the Pittsburgh Epidemiology of Diabetes Complications (EDC) study and the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: Evidence suggests that insulin deficiency and hyperglycemia may disrupt the female reproductive system's normal function, leading to delayed menarche and premature ovarian aging. We thus compared the length of the reproductive period of women with type 1 diabetes (T1D) to women without diabetes. METHODS: Women with childhood-onset T1D (diagnosed in 1950-80) from the prospective Epidemiology of Diabetes Complications (EDC) study and nondiabetic women from the Pittsburgh site of the Study of Women's Health Across the Nation (SWAN) were studied. Exclusion criteria comprised not having reached natural menopause, hysterectomy/oophorectomy before menopause, and sex hormone therapy during the menopausal transition. Reproductive history was self-reported. The historical and Women's Ischemia Syndrome Evaluation hormonal algorithms were also used to assess menopause status. RESULTS: Women in the T1D cohort (n = 105) were younger, more likely to be White, never smokers, with lower BMI and higher high-density lipoprotein cholesterol levels (all P values < 0.05) compared with women without diabetes (n = 178). After covariate adjustment, T1D women were also older at menarche (0.5-y delay, P = 0.002) but younger at natural menopause (-2.0 y, P < 0.0001). Women with T1D thus experienced 2.5 fewer reproductive years compared to those without diabetes (P < 0.0001). These findings were restricted to the subgroup of women who were diagnosed with T1D before reaching menarche (n = 80). CONCLUSION: Women with T1D onset before menarche have a shorter reproductive period compared with nondiabetic women, exhibiting delayed menarche and earlier natural menopause. Factors that may be related to a shorter reproductive period in T1D should be investigated.

High-Sensitivity Cardiac Troponin-T and N-Terminal Prohormone of B-Type Natriuretic Peptide in Relation to Cardiovascular Outcomes in Type 1 Diabetes.

OBJECTIVE: High-sensitivity cardiac troponin-T (hs-cTnT) and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), biomarkers of cardiovascular disease (CVD) and heart failure, respectively, have not been widely studied in type 1 diabetes (T1D). We evaluated whether their assessment in T1D enhances the prediction of CVD and major adverse cardiovascular events (MACE). RESEARCH DESIGN AND METHODS: hs-cTnT and NT-proBNP were analyzed on the Roche Cobas E601 using the first available stored specimen (n = 581; mean age 29 years and diabetes duration 21 years). CVD was defined as CVD death, myocardial infarction, coronary revascularization, angina, ischemia, or stroke, and MACE as CVD death, myocardial infarction, or stroke. RESULTS: Median hs-cTnT (5.0 ng/L; interquartile range <3.0, 10.0) was higher among men (P < 0.0001), whereas median NT-proBNP (22.0 ng/L; 7.0, 61.0) did not differ by sex. In Cox models, log hs-cTnT (hazard ratio [HR] 1.38, P = 0.0006) and log NT-proBNP (HR 1.24, P = 0.0001) independently predicted CVD during 21 years of follow-up. However, their addition to models, singly or together, did not significantly improve CVD prediction. Furthermore, a marginally significant sex interaction was observed (P = 0.06), indicating that the hs-cTnT prediction was limited to men. hs-cTnT and NT-proBNP also predicted MACE, although only NT-proBNP remained significant (HR 1.27, P = 0.0009) when the biomarkers were included in a model simultaneously. Nonetheless, their addition to multivariable models did not enhance MACE prediction. CONCLUSIONS: Sex differences were observed in the concentration and predictive ability of hs-cTnT and NT-proBNP in T1D. Overall, their addition to traditional risk factor models increased the area under the curve for neither CVD nor MACE.

Optimal Blood Pressure Thresholds for Minimal Coronary Artery Disease Risk in Type 1 Diabetes.

OBJECTIVE: We aimed to determine optimal blood pressure (BP) thresholds for minimizing coronary artery disease (CAD) risk in people with childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study participants without known CAD at baseline (n = 605) were included and followed for 25 years. The associations of time-weighted BP measures (systolic BP [SBP], diastolic BP [DBP], and mean arterial pressure) with incident CAD were examined by using Cox models. Areas under the receiver operating characteristic curve (AUC) were summarized by different cut points of time-weighted BPs. Risk stratification analyses were then performed on the basis of BP (<120/80 vs. ≥120/80 mmHg) and HbA1c (<8% vs. ≥8%). RESULTS: Baseline mean age was 27 years. Half of the cohort were women and 98% were white. A dose-gradient association was observed for categorized time-weighted BPs and CAD. According to AUC, the optimal cut point for SBP was 120 mmHg and for DBP was 80 mmHg. BP ≥120/80 mmHg was associated with a 1.9 times (95% CI 1.4, 2.6) greater risk of developing CAD than that for BP <120/80 mmHg. Participants with good control of both BP and HbA1c had BP <120/80 mmHg and HbA1c <8%. Those with only high BP (hazard ratio [HR] 2.0 [95% CI 1.1, 3.9]) carried a similar risk of developing CAD as those with only high HbA1c (HR 1.6 [95% CI 0.97, 2.8]). CONCLUSIONS: The optimal BP threshold associated with minimal CAD risk is 120/80 mmHg in young adults with childhood-onset type 1 diabetes.

Risk Factor Modeling for Cardiovascular Disease in Type 1 Diabetes in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study: A Comparison With the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC).

In a recent Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study report, mean HbA1c was the strongest predictor of cardiovascular disease (CVD) after age. In DCCT/EDIC, mean diabetes duration was 6 years (median 4) at baseline and those with high blood pressure or cholesterol were excluded. We now replicate these analyses in the Pittsburgh Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset (at <17 years of age) type 1 diabetes, with similar age (mean 27 years in both studies) but longer diabetes duration (mean 19 years and median 18 years) and no CVD risk factor exclusion at baseline. CVD incidence (CVD death, myocardial infarction (MI), stroke, revascularization, angina, or ischemic electrocardiogram) was associated with diabetes duration, most recent albumin excretion rate (AER), updated mean triglycerides, baseline hypertension, baseline LDL cholesterol, and most recent HbA1c Major atherosclerotic cardiovascular events (CVD death, MI, or stroke) were associated with diabetes duration, most recent AER, baseline systolic blood pressure, baseline smoking, and updated mean HbA1c Compared with findings in DCCT/EDIC, traditional risk factors similarly predicted CVD; however AER predominates in EDC and HbA1c in DCCT/EDIC. Thus, the relative impact of HbA1c and kidney disease in type 1 diabetes varies according to diabetes duration.

Dietary Patterns Over Time and Microalbuminuria in Youth and Young Adults With Type 1 Diabetes: The SEARCH Nutrition Ancillary Study.

OBJECTIVE: We assessed the association between diet quality and microalbuminuria in youth-onset type 1 diabetes using three indices: a modified Mediterranean diet score for children and adolescents (mKIDMED), the Dietary Approaches to Stop Hypertension (DASH), and the Healthy Eating Index-2010 (HEI). RESEARCH DESIGN AND METHODS: Youth and young adults from the SEARCH (SEARCH for Diabetes in Youth) Nutrition Ancillary Study (SNAS) diagnosed with type 1 diabetes in 2002-2008, who had repeated dietary assessments at baseline and follow-up visits and urine albumin-to-creatinine ratio (UACR) measured at the outcome visit (2012-2015) (n = 461), were selected for study. Regression models estimated the association between each longitudinally assessed diet score and UACR and microalbuminuria (UACR ≥30 µg/mg). RESULTS: The cohort was 43% female, and at follow-up, mean age was 20 years, disease duration was 108 months, and 7% had microalbuminuria. Adherence to a higher-quality diet was low for the mKIDMED (mean 3.7 of a possible range of -3 to 12) and the DASH (mean 42 of 80) and better, for the HEI (mean 56.3 of 100). A borderline inverse association was observed between the HEI score and microalbuminuria after adjustment for caloric and protein intake and demographic and disease factors (odds ratio [OR]HEI 0.83, P = 0.07), which lost significance with further adjustment for HbA1c and systolic blood pressure (ORHEI 0.86, P = 0.19). Results were similar for continuous UACR. No significant associations were observed for diet quality characterized by the mKIDMED or DASH indices. CONCLUSIONS: Greater adherence to the HEI may be beneficial for kidney health in youth and young adults with type 1 diabetes. Low adherence to the mKIDMED and DASH diets may explain the lack of association with microalbuminuria.

Cumulative Kidney Complication Risk by 50 Years of Type 1 Diabetes: The Effects of Sex, Age, and Calendar Year at Onset.

OBJECTIVE: A common belief is that only a minority of patients with type 1 diabetes (T1D) develop advanced kidney disease and that incidence is higher among men and lower in those diagnosed at a younger age. However, because few patients with T1D survived to older ages until recently, long-term risks have been unclear. RESEARCH DESIGN AND METHODS: We examined the 50-year cumulative kidney complication risk in a childhood-onset T1D cohort diagnosed during 1950-80 (n = 932; mean baseline age 29 years, duration 19 years). Participants comprised 144 who died prior to baseline, 130 followed with periodic surveys, and 658 followed with biennial surveys and a maximum of nine examinations for 25 years. Micro- and macroalbuminuria were defined as an albumin excretion rate of 20-199 and ≥200 µg/min, respectively, and end-stage renal disease (ESRD) was defined as dialysis or kidney transplantation. Cumulative incidence was estimated at 10-year intervals between 20 and 50 years, duration and compared by calendar year of diabetes onset. RESULTS: By 50 years, T1D duration, ESRD affected 60% of the cohort; macroalbuminuria, 72%; and microalbuminuria, 88%. Little evidence existed for declines in cumulative incidence in recent cohorts, except for ESRD (microalbuminuria 3% increase, macroalbuminuria no change; ESRD 45% decrease by 40 years of T1D duration). Onset before age 6 years was associated with the lowest risk; incidence generally did not differ by sex. CONCLUSIONS: Some degree of kidney disease in T1D is virtually universal at long durations and not declining, which has major implications for formulating health care and research strategies. ESRD has declined, but continues to affect >25% of the population by 40 years, duration.

Physical activity and hippocampal volume in middle-aged patients with type 1 diabetes.

OBJECTIVE: To examine the cross-sectional association between physical activity (PA) and hippocampal volume in middle-aged adults with childhood-onset type 1 diabetes (T1D), and whether hyperglycemia and insulin sensitivity contribute to this relationship. METHODS: We analyzed neuroimaging and self-reported PA data from 79 adults with T1D from the Pittsburgh Epidemiology of Diabetes Complications Study (mean age 50 years, mean duration 41 years) and 122 similarly aged adults without T1D (mean age 48 years). Linear regression models, controlling for intracranial volume, sex, education, and age, tested associations between PA and gray matter volumes of hippocampi and total brain in the 2 groups. For the T1D group, models further controlled for hyperglycemia and glucose disposal rate, a measure of insulin sensitivity. RESULTS: PA was significantly lower in the T1D than in the non-T1D group (median [interquartile range] 952 kcal [420-2,044] vs 1,614 kcal [588-3,091], respectively). Higher PA was significantly associated with larger hippocampi for T1D, but not for non-T1D (standardized ß [p values] from regression models adjusted for intracranial volume, sex, age, and education: 0.270 [p < 0.001] and 0.098 [p = 0.12], respectively). Neither hyperglycemia nor glucose disposal rate substantially modified this association. Relationships between PA and total brain gray matter volume were similar. CONCLUSIONS: A cross-sectional association between higher PA and larger hippocampi is already detectable by middle age for these patients with T1D, and it appears robust to chronic hyperglycemia and insulin sensitivity. Proof-of-concept studies should investigate whether increasing PA preserves hippocampal volume and the mechanisms underlying the effects of PA on hippocampal volume.

A Contemporary Estimate of Total Mortality and Cardiovascular Disease Risk in Young Adults With Type 1 Diabetes: The Pittsburgh Epidemiology of Diabetes Complications Study.

OBJECTIVE: The degree to which mortality and cardiovascular disease (CVD) incidence remains elevated in young U.S. adults with type 1 diabetes (T1DM) is unclear. We determined contemporary rates for adults <45 years old with long-standing, childhood-onset T1DM from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. RESEARCH DESIGN AND METHODS: Members of the EDC Study cohort <45 years old during the 1996-2012 follow-up period (n = 502) were studied. Mortality and CVD rates were calculated for those aged 30-39 and 40-44 years. Data from the background Allegheny County, Pennsylvania, population were used to calculate age- and sex-matched standardized mortality (SMR) and incidence rate ratios (IRR). RESULTS: In both age groups, the SMR for total mortality was ∼5 (95% CIs: 30-39-year-olds, 2.8, 7.2; 40-44-year-olds, 3.4, 7.8). CVD mortality SMRs ranged from 19 (95% CI 11, 32) to 33 (95% CI 17, 59). Hospitalized CVD IRR was ∼8 (95% CIs: 30-39-year-olds, 2.5, 18.9; 40-44-year-olds, 4.5, 12.8); revascularization procedures account for much of the increased risk. For all outcomes, the relative risk was larger in women. Participants aged 30-39 years had 6.3% (95% CI 3.8, 9.8) absolute 10-year CVD risk, approaching the American College of Cardiology/American Heart Association-recommended cut point of 7.5% for initiation of statin therapy in older adults. CONCLUSIONS: Total and CVD mortality and hospitalized CVD are all significantly increased in this contemporary U.S. cohort of young adults with long-standing T1DM. These findings support more aggressive risk factor management in T1DM, especially among women.

Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes.

OBJECTIVE: The aim of this study was to investigate the presence and correlates of clinically relevant cognitive impairment in middle-aged adults with childhood-onset type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: During 2010-2013, 97 adults diagnosed with T1D and aged <18 years (age and duration 49 ± 7 and 41 ± 6 years, respectively; 51% female) and 138 similarly aged adults without T1D (age 49 ± 7 years; 55% female) completed extensive neuropsychological testing. Biomedical data on participants with T1D were collected periodically since 1986-1988. Cognitive impairment status was based on the number of test scores ≥1.5 SD worse than demographically appropriate published norms: none, mild (only one test), or clinically relevant (two or more tests). RESULTS: The prevalence of clinically relevant cognitive impairment was five times higher among participants with than without T1D (28% vs. 5%; P < 0.0001), independent of education, age, or blood pressure. Effect sizes were large (Cohen d 0.6-0.9; P < 0.0001) for psychomotor speed and visuoconstruction tasks and were modest (d 0.3-0.6; P < 0.05) for measures of executive function. Among participants with T1D, prevalent cognitive impairment was related to 14-year average A1c >7.5% (58 mmol/mol) (odds ratio [OR] 3.0; P = 0.009), proliferative retinopathy (OR 2.8; P = 0.01), and distal symmetric polyneuropathy (OR 2.6; P = 0.03) measured 5 years earlier; higher BMI (OR 1.1; P = 0.03); and ankle-brachial index ≥1.3 (OR 4.2; P = 0.01) measured 20 years earlier, independent of education. CONCLUSIONS: Clinically relevant cognitive impairment is highly prevalent among these middle-aged adults with childhood-onset T1D. In this aging cohort, chronic hyperglycemia and prevalent microvascular disease were associated with cognitive impairment, relationships shown previously in younger populations with T1D. Two additional potentially modifiable risk factors for T1D-related cognitive impairment, vascular health and BMI, deserve further study.

The haptoglobin 1 allele correlates with white matter hyperintensities in middle-aged adults with type 1 diabetes.

Although the haptoglobin (Hp) 1-1 genotype is associated with a lower coronary artery disease (CAD) risk in diabetes, we recently reported an increased stroke incidence in type 1 diabetes with Hp 1-1. We, thus, evaluated differences in earlier brain vascular abnormality markers by Hp using neuroimaging. Neuroimaging was completed in 94 participants of the Pittsburgh Epidemiology of Diabetes Complications study with Hp genotyping available (mean age, 49; duration, 41 years). White matter hyperintensities (WMH) volume, lacunar infarcts, and gray matter atrophy were quantified. Sixteen percent were homozygous for Hp 1 and 43% for Hp 2. A significant trend toward increased WMH was observed with greater duration and the number of Hp 1 alleles. Associations were strongest for the interhemispheric connecting fibers of the corpus callosum. Allowing for duration, sex, waist-to-hip ratio, HbA1c, systolic blood pressure, and lipids in models with backward elimination, results were similar. No significant differences by Hp were noted for atrophy or lacunar infarcts. Consistent with its direct association with stroke, the Hp 1-1 genotype is associated with higher WMH in this population. Further, including mechanistic, studies on the role of the Hp genotype in cerebrovascular disease and the implications for worsening cognitive function are needed.