Duration of diabetes and degree of hyperglycemia have consistently been identified as predictors of retinopathy and nephropathy (1–6). Multiple studies have concluded that nearly all individuals with type 1 diabetes will develop some level of retinopathy within 20 years of diagnosis (2,4,5,7,8). However, the study by Bain et al. (9) described the Golden Years study group of type 1 diabetic patients with ≥50 years of diabetes duration who appeared to be protected against nephropathy and large vessel disease but not against retinopathy. However, the associations of glycemic control, duration of disease, and vascular complications were not evaluated (9). This report characterizes the prevalence of complications and associated risk factors in a large number of individuals who have been insulin dependent for ≥50 years.
The 50-Year Medal Program of the Joslin Diabetes Center (JDC) was initiated to recognize JDC or non-JDC patients who survived ≥50 years with type 1 diabetes. This was documented by either medical record or family report. This was a survey-based cross-sectional study of subjects living in the U.S. who were awarded the Joslin Medal between 1997 and 2003. The Committee on Human Subjects at the JDC approved this study. The patients were questioned regarding the presence and absence of eye, kidney, and peripheral neuropathy.
### Clinical validation of retinopathy
Self-reported retinopathy was validated by comparing retinal clinical examination and fundus photography (seven-standard field), in a subset ( n = 92, 28%) of the 326 subjects, to the questionnaire, with the worse eye used for analysis. Grading was performed by two experienced ophthalmologists and discrepancies adjudicated by consensus. Descriptive analyses were performed using the Statistical Analysis System (version 8.2; SAS, Cary, NC). The Cochran-Armitage test was used to test for trends of categorical …
OBJECTIVE—Clinical cardiovascular disease (CVD) is highly prevalent among people with diabetes. However, there is little information regarding the prevalence of subclinical CVD and its relation to clinical CVD in diabetes and in the glucose disorders that precede diabetes. RESEARCH DESIGN AND METHODS—Participants in the Cardiovascular Health Study, aged ≥65 years (n = 5,888), underwent vascular and metabolic testing. Individuals with known disease in the coronary, cerebral, or peripheral circulations were considered to have clinical disease. Those without any clinical disease in whom CVD was detected by ultrasonography, electrocardiography, or ankle arm index in any of the three vascular beds were considered to have isolated subclinical disease. RESULTS—Approximately 30% of the cohort had clinical disease, and ∼60% of the remainder had isolated subclinical disease. In those with normal glucose status, isolated subclinical disease made up most of the total CVD. With increasing glucose severity, the proportion of total CVD that was clinical disease increased; 75% of men and 66% of women with normal fasting glucose status had either clinical or subclinical CVD. Among those with known diabetes, the prevalence was ∼88% (odds ratio [OR] 2.46 for men and 4.22 for women, P < 0.0001). There were intermediate prevalences and ORs for those with impaired fasting glucose status and newly diagnosed diabetes. CONCLUSIONS—Isolated subclinical CVD is common among older adults. Glucose disorders are associated with an increased prevalence of total CVD and an increased proportion of clinical disease relative to subclinical disease.
Background: Medial arterial calcification (MAC) is common in diabetes, has a characteristic “tram-track” appearance on x-ray and has been linked with peripheral arterial stiffness, CVD events, and all-cause mortality. While the ankle brachial index (ABI) is often available in epidemiologic studies, few studies have measured MAC by x-ray. It has been suggested that an ABI > 1.30 or ankle brachial difference (ABD) > 75mmHg may identify individuals with MAC, but the test characteristics of the ABI and ABD for MAC are uncertain. Methods: Among 185 individuals with type 1 diabetes, we measured ankle and brachial SBP and calculated the ABI and ABD. Lower limb x-rays where read for MAC by two physician investigators and independently reviewed by investigators in the Netherlands. Only linear calcification was considered diagnostic of MAC. The Kappa statistic for any versus none was 0.89 for the two sets of scores. We determined the area under the receiver operator curve (ROC) of the ABI and ABD for MAC on x-ray. and also evaluated the test characteristics at various ABI and ABD cut-points. Results: The mean age was 32±6 years and mean diabetes duration was 23±7 years. 97 individuals (57%) had MAC, 15 (8%) had ABI > 1.30, and 14 (8%) had ABD > 75mmHg. The area under the ROC of the ABI for MAC was modest (0.65) and was slightly higher for the ABD (0.75). Table 1 shows the test characteristics of different ABI and ABD cut-points. Both ABI > 1.30 and ABD > 75mmHg were highly specific for MAC, but with poor sensitivity. Conclusions: Individuals with type 1 diabetes who have an ABI > 1.30 or ABD > 75mmHg are very likely to have MAC on x-ray, however many individuals with MAC will not have ABI or ABD above these thresholds. Given high specificity, in studies without x-rays, evaluating high ABI or ABD as surrogates of MAC may prove useful to identify MAC risk factors, but may underestimate the prevalence of MAC. Table 1. Test Characteristics of the ABI and ABD for X-ray Medial Arterial Calcification in Type 1 Diabetes Ankle Brachial Index ABI n (%) Sensitivity Specificity PPV NPV Accuracy > 1.05 125 (68%) 70% 35% 54% 52% 54% > 1.10 84 (45%) 57% 67% 65% 58% 62% > 1.20 38 (21%) 32% 92% 82% 55% 61% > 1.30 15 (8%) 14% 99% 93% 51% 55% > 1.40 7 (4%) 7% 100% 100% 49% 51% Ankle Brachial Difference ABD (mmHg) n (%) Sensitivity Specificity PPV NPV Accuracy > 15 133 (72%) 83% 49% 60^ 67% 62% > 20 115 (62%) 78% 56% 66% 70% 68% > 25 84 (46%) 66% 77% 76% 67% 71% > 50 31 (17%) 30% 98% 94% 56% 62% > 75 14 (8%) 14% 100% 100% 52% 55%
Although coronary artery disease (CAD) is the leading cause of death in type 1 diabetes (T1D), the mechanisms responsible for the greatly increased risk are poorly understood. In particular, the role of glycaemic control is controversial with one study suggesting it predicts CAD mortality but not incidence. In this analysis, of the Pittsburgh Epidemiology of Diabetes Complications study cohort of T1D, we examine whether risk factors differ for CAD morbidity and mortality, with a specific focus on HbA1c and insulin dose. Participants ( n=592) were followed for 18 years for incident non-fatal and fatal CAD. Cox stepwise regression was used to determine the independent risk factors for non-fatal and fatal CAD. Mean age and diabetes duration at study baseline were 29 and 20 years, respectively. There were 109 incident non-fatal and 48 fatal CAD events. Baseline HbA 1C was an independent risk factor for fatal CAD, along with duration of diabetes and albuminuria. In contrast, baseline lower insulin dose was strongly predictive of non-fatal CAD, as was lower renal function, higher diastolic blood pressure, and lipids. HbA 1C predicts CAD mortality while lower insulin dose and standard CAD risk factors predict CAD morbidity.
Objective: High-sensitivity cardiac Troponin-T (hs-cTnT) and N-terminal pro 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 atherosclerotic cardiovascular events (MACE). <p> </p> <p>Research Design and Methods: hs-cTnT and NT-proBNP were analyzed on the Roche Cobas E601 utilizing the first available stored specimen (n=581; mean age 29 and 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.</p> <p> </p> <p>Results: Median hs-cTnT (5.0 ng/L, IQR: <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 (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 either singly or together did not significantly improve CVD prediction. Furthermore, a marginally significant sex interaction was observed (p=0.06), indicating that hs-cTnT’s 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.</p> <p> </p> <p> </p> <p>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.</p>
The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) 3rd expert report highlights up-to-date Cancer Prevention Recommendations that may reduce burdens of many chronic diseases, including diabetes. This study examined if following a lifestyle that aligns with the recommendations - assessed via the 2018 WCRF/AICR Score - was associated with lower risk of type 2 diabetes in high-risk adults participating in the Diabetes Prevention Program Outcomes Study (DPPOS).The Diabetes Prevention Program (DPP) randomized adults at high risk for diabetes to receive a lifestyle intervention (ILS), metformin (MET) or a placebo (PLB) (mean: 3.2 years), with additional follow-up in DPPOS for 11 years (mean: 15 years total). 2018 WCRF/AICR Scores included seven components: body weight, physical activity, plant-based foods, fast foods, red and processed meat, sugar-sweetened beverages, and alcohol; the optional breastfeeding component was excluded. Scores ranged 0-7 points (with greater scores indicating greater alignment with the recommendations) and were estimated at years 0, 1, 5, 6, 9, and 15 (N=3,147). Fasting glucose and HbA1c were measured every six months and oral glucose tolerance tests were performed annually. Adjusted Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) were used to examine the association of both Score changes from years 0-1 and time-dependent Score changes on diabetes risk through DPP and year 15.Scores improved within all groups over 15 years (p<0.001); ILS Scores improved more than MET or PLB Scores after 1 year (p<0.001). For every 1-unit improvement from years 0-1, there was a 31% and 15% lower diabetes risk in ILS (95% CI: 0.56-0.84) and PLB (95% CI: 0.72-0.97) through DPP, and no significant association in MET. Associations were greatest among American Indian participants, followed by non-Hispanic White and Hispanic participants. Score changes from years 0-1 and time-dependent Score changes in ILS and PLB remained associated with lower risk through year 15.Score improvements were associated with long-term, lower diabetes risk among high-risk adults randomized to ILS and PLB, but not MET. Future research should explore impact of the Score on cancer risk.Diabetes Prevention Program: NCT00004992 ; Diabetes Prevention Program Outcomes Study: NCT00038727.
