Stephanie D’Eon

Cardiovascular Disease Protection in Long-Duration Type 1 Diabetes and Sex Differences

Two recent articles describe higher morbidity and mortality from cardiovascular disease (CVD) at younger ages for women with type 1 diabetes compared with men in cohorts with average duration of approximately 30 years (1,2). Women in the Joslin 50-Year Medalist Study (total n = 680) have a significantly lower CVD prevalence than men (women 35.3% vs. men 51.6%, P < 0.001), suggesting a protective factor. The objective of this analysis was to investigate protective factors associated with CVD and sex-associated differences in rates in those with long-term type 1 diabetes. The Joslin 50-Year Medalist Study is a cross-sectional study of individuals with 50 or more years of type 1 diabetes ( n = 651). To be awarded the Joslin 50-Year Medal, individuals provide an original medical record from time of diagnosis, or three other forms of documentation of insulin dependence since the time of diagnosis 50 or more …

Association of Glycemic Control With Reduced Risk for Large-Vessel Disease After More Than 50 Years of Type 1 Diabetes

Context Previously we demonstrated, in individuals who have had type 1 diabetes (T1D) for 50 or more years (Medalists), that glycemic control was unrelated to diabetic complications, with the exception of cardiovascular disease (CVD), contrary to what has been documented in registry-based studies. Objective The purpose of this study is to validate these initial findings and identify contributors to mortality on an individual basis in a large cohort. Design Cross-sectional and longitudinal study. Setting Joslin Diabetes Center (JDC), Boston, Massachusetts. Patients 50-year Medalists presenting to JDC for study participation. Interventions None. Main Outcomes Measures Microvascular and macrovascular complications of diabetes and mortality. Results Glycemic control was not significantly associated with small-vessel complications in Medalists but was associated with CVD in the overall cohort, yet with varying effect by tertile of cohort duration. CVD was the largest contributor to mortality, whereas hemoglobin A1c was not an independent predictor of mortality either overall or substantially by diagnosis interval. Additionally, exercise mitigated mortality risk imparted by CVD. Conclusions Few large populations with long duration of (T1D) have been available to examine the effects of long-term exposure to hyperglycemia. These data indicate that an association of glycemic control, complications, and mortality may change in an older population with T1D. These results suggest that careful control is still warranted in older populations with T1D.

Diabetes Care Disparities in Long-standing Type 1 Diabetes in Canada and the U.S.: A Cross-sectional Comparison

OBJECTIVE To assess national differences in diabetes care and quality of life (QOL) between individuals with long-standing type 1 diabetes (≥50 years) in Canada and the U.S. RESEARCH DESIGN AND METHODS Cross-sectional data from identical surveys administered in the Canadian Study of Longevity in Diabetes and the Joslin Medalist Study, collected in 2013–2016 and 2005–2011, respectively, were compared. Laboratory values and ophthalmic examination were completed by clinical care physicians for Canadians and the Joslin Clinic for Americans. Univariate comparisons and multivariable regression for HbA1c, QOL, insulin pump use, and coronary artery disease (CAD) were performed. Nephropathy, CAD, and peripheral arterial disease (PAD) were self-reported; neuropathy was defined by a Michigan Neuropathy Screening Instrument (Questionnaire component) score ≥3, and proliferative retinopathy was documented from ophthalmic examination. QOL was self-reported on an ordinal scale. RESULTS Three hundred sixty-one Canadians and 668 Americans had similar ages (mean 65.78 years [SD 8.67] vs. 66.38 years [7.66], P = 0.27) and durations of diabetes (median 53.00 years [interquartile range 51.00, 58.00] vs. 53.00 years [51.00, 57.00], P = 0.51). Canadians had higher HbA1c (mean 7.53% [SD 1.03] [59 mmol/mol] vs. 7.22% [0.98] [55 mmol/mol], P < 0.0001), lower QOL (36.9% vs. 48.7% with “excellent” QOL, P = 0.0002), and less CAD (29.7% vs. 41.2%, P = 0.0003) and insulin pump use (43.3% vs. 55.6%, P = 0.0002). Other complication rates were similar. Residual differences for Canadians compared with Americans remained after adjustment for age, sex, CAD, PAD, education, and relevant a priori selected variables: 0.28% higher HbA1c (P = 0.0004); and odds ratios of 0.68 (95% CI 0.51, 0.90), 0.46 (0.31, 0.68), and 0.71 (0.52, 0.96) for higher QOL, CAD, and insulin pump use, respectively. CONCLUSIONS Although Canadians and Americans have similar rates of complications other than CAD, further research is required to understand why Canadians have higher HbA1c levels, lower QOL, and less insulin pump use.

Differential Association of Microvascular Attributions With Cardiovascular Disease in Patients With Long Duration of Type 1 Diabetes

OBJECTIVE Independent association of chronic kidney disease (CKD) and proliferative diabetic retinopathy (PDR) with cardiovascular disease (CVD) has not been established. In the Joslin 50-Year Medalist study, characterizing individuals with type 1 diabetes for 50 years or more, we examined the associations of CKD and PDR with CVD, which was validated by another cohort with type 1 diabetes from Finland. RESEARCH DESIGN AND METHODS This cross-sectional study characterized U.S. residents (n = 762) with type 1 diabetes of 50 years or longer (Medalists) at a single site by questionnaire, clinical, ophthalmic, and laboratory studies. A replication cohort (n = 675) from the longitudinal Finnish Diabetic Nephropathy Study (FinnDiane) was used. CKD and PDR were defined as estimated glomerular filtration rate <45 mL/min/1.73 m2 (CKD stage 3b) and according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, respectively. CVD was based on questionnaires and/or hospital discharge registers. Associations of CVD status with CKD and PDR were analyzed by multivariable logistic regression. RESULTS CVD prevalence in the Medalists with CKD and without PDR (+CKD/−PDR) (n = 30) and CVD prevalence in the −CKD/+PDR group (n = 339) were half the prevalence in the +CKD/+PDR group (n = 66) (34.5% and 42.8% vs. 68.2%, P = 0.002). PDR status was independently associated with CVD (odds ratio 0.21 [95% CI 0.08–0.58], P = 0.003) in patients with CKD. Among the Finnish cohort, a trend toward a lower prevalence of CVD in the +CKD/−PDR group (n = 21) compared with the +CKD/+PDR group (n = 170) (19.1% vs. 37.1%, P = 0.10) was also observed. CONCLUSIONS Absence of PDR in people with type 1 diabetes and CKD was associated with a decreased prevalence of CVD, suggesting that common protective factors for PDR and CVD may exist.

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OBJECTIVE To assess national differences in diabetes care and quality of life (QOL) between individuals with long-standing type 1 diabetes (≥50 years) in Canada and the U.S. RESEARCH DESIGN AND METHODS Cross-sectional data from identical surveys administered in the Canadian Study of Longevity in Diabetes and the Joslin Medalist Study, collected in 2013–2016 and 2005–2011, respectively, were compared. Laboratory values and ophthalmic examination were completed by clinical care physicians for Canadians and the Joslin Clinic for Americans. Univariate comparisons and multivariable regression for HbA1c, QOL, insulin pump use, and coronary artery disease (CAD) were performed. Nephropathy, CAD, and peripheral arterial disease (PAD) were self-reported; neuropathy was defined by a Michigan Neuropathy Screening Instrument (Questionnaire component) score ≥3, and proliferative retinopathy was documented from ophthalmic examination. QOL was self-reported on an ordinal scale. RESULTS Three hundred sixty-one Canadians and 668 Americans had similar ages (mean 65.78 years [SD 8.67] vs. 66.38 years [7.66], P = 0.27) and durations of diabetes (median 53.00 years [interquartile range 51.00, 58.00] vs. 53.00 years [51.00, 57.00], P = 0.51). Canadians had higher HbA1c (mean 7.53% [SD 1.03] [59 mmol/mol] vs. 7.22% [0.98] [55 mmol/mol], P < 0.0001), lower QOL (36.9% vs. 48.7% with “excellent” QOL, P = 0.0002), and less CAD (29.7% vs. 41.2%, P = 0.0003) and insulin pump use (43.3% vs. 55.6%, P = 0.0002). Other complication rates were similar. Residual differences for Canadians compared with Americans remained after adjustment for age, sex, CAD, PAD, education, and relevant a priori selected variables: 0.28% higher HbA1c (P = 0.0004); and odds ratios of 0.68 (95% CI 0.51, 0.90), 0.46 (0.31, 0.68), and 0.71 (0.52, 0.96) for higher QOL, CAD, and insulin pump use, respectively. CONCLUSIONS Although Canadians and Americans have similar rates of complications other than CAD, further research is required to understand why Canadians have higher HbA1c levels, lower QOL, and less insulin pump use.

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OBJECTIVE To assess national differences in diabetes care and quality of life (QOL) between individuals with long-standing type 1 diabetes (≥50 years) in Canada and the U.S. RESEARCH DESIGN AND METHODS Cross-sectional data from identical surveys administered in the Canadian Study of Longevity in Diabetes and the Joslin Medalist Study, collected in 2013–2016 and 2005–2011, respectively, were compared. Laboratory values and ophthalmic examination were completed by clinical care physicians for Canadians and the Joslin Clinic for Americans. Univariate comparisons and multivariable regression for HbA1c, QOL, insulin pump use, and coronary artery disease (CAD) were performed. Nephropathy, CAD, and peripheral arterial disease (PAD) were self-reported; neuropathy was defined by a Michigan Neuropathy Screening Instrument (Questionnaire component) score ≥3, and proliferative retinopathy was documented from ophthalmic examination. QOL was self-reported on an ordinal scale. RESULTS Three hundred sixty-one Canadians and 668 Americans had similar ages (mean 65.78 years [SD 8.67] vs. 66.38 years [7.66], P = 0.27) and durations of diabetes (median 53.00 years [interquartile range 51.00, 58.00] vs. 53.00 years [51.00, 57.00], P = 0.51). Canadians had higher HbA1c (mean 7.53% [SD 1.03] [59 mmol/mol] vs. 7.22% [0.98] [55 mmol/mol], P < 0.0001), lower QOL (36.9% vs. 48.7% with “excellent” QOL, P = 0.0002), and less CAD (29.7% vs. 41.2%, P = 0.0003) and insulin pump use (43.3% vs. 55.6%, P = 0.0002). Other complication rates were similar. Residual differences for Canadians compared with Americans remained after adjustment for age, sex, CAD, PAD, education, and relevant a priori selected variables: 0.28% higher HbA1c (P = 0.0004); and odds ratios of 0.68 (95% CI 0.51, 0.90), 0.46 (0.31, 0.68), and 0.71 (0.52, 0.96) for higher QOL, CAD, and insulin pump use, respectively. CONCLUSIONS Although Canadians and Americans have similar rates of complications other than CAD, further research is required to understand why Canadians have higher HbA1c levels, lower QOL, and less insulin pump use.

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OBJECTIVE To assess national differences in diabetes care and quality of life (QOL) between individuals with long-standing type 1 diabetes (≥50 years) in Canada and the U.S. RESEARCH DESIGN AND METHODS Cross-sectional data from identical surveys administered in the Canadian Study of Longevity in Diabetes and the Joslin Medalist Study, collected in 2013–2016 and 2005–2011, respectively, were compared. Laboratory values and ophthalmic examination were completed by clinical care physicians for Canadians and the Joslin Clinic for Americans. Univariate comparisons and multivariable regression for HbA1c, QOL, insulin pump use, and coronary artery disease (CAD) were performed. Nephropathy, CAD, and peripheral arterial disease (PAD) were self-reported; neuropathy was defined by a Michigan Neuropathy Screening Instrument (Questionnaire component) score ≥3, and proliferative retinopathy was documented from ophthalmic examination. QOL was self-reported on an ordinal scale. RESULTS Three hundred sixty-one Canadians and 668 Americans had similar ages (mean 65.78 years [SD 8.67] vs. 66.38 years [7.66], P = 0.27) and durations of diabetes (median 53.00 years [interquartile range 51.00, 58.00] vs. 53.00 years [51.00, 57.00], P = 0.51). Canadians had higher HbA1c (mean 7.53% [SD 1.03] [59 mmol/mol] vs. 7.22% [0.98] [55 mmol/mol], P < 0.0001), lower QOL (36.9% vs. 48.7% with “excellent” QOL, P = 0.0002), and less CAD (29.7% vs. 41.2%, P = 0.0003) and insulin pump use (43.3% vs. 55.6%, P = 0.0002). Other complication rates were similar. Residual differences for Canadians compared with Americans remained after adjustment for age, sex, CAD, PAD, education, and relevant a priori selected variables: 0.28% higher HbA1c (P = 0.0004); and odds ratios of 0.68 (95% CI 0.51, 0.90), 0.46 (0.31, 0.68), and 0.71 (0.52, 0.96) for higher QOL, CAD, and insulin pump use, respectively. CONCLUSIONS Although Canadians and Americans have similar rates of complications other than CAD, further research is required to understand why Canadians have higher HbA1c levels, lower QOL, and less insulin pump use.

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OBJECTIVE To assess national differences in diabetes care and quality of life (QOL) between individuals with long-standing type 1 diabetes (≥50 years) in Canada and the U.S. RESEARCH DESIGN AND METHODS Cross-sectional data from identical surveys administered in the Canadian Study of Longevity in Diabetes and the Joslin Medalist Study, collected in 2013–2016 and 2005–2011, respectively, were compared. Laboratory values and ophthalmic examination were completed by clinical care physicians for Canadians and the Joslin Clinic for Americans. Univariate comparisons and multivariable regression for HbA1c, QOL, insulin pump use, and coronary artery disease (CAD) were performed. Nephropathy, CAD, and peripheral arterial disease (PAD) were self-reported; neuropathy was defined by a Michigan Neuropathy Screening Instrument (Questionnaire component) score ≥3, and proliferative retinopathy was documented from ophthalmic examination. QOL was self-reported on an ordinal scale. RESULTS Three hundred sixty-one Canadians and 668 Americans had similar ages (mean 65.78 years [SD 8.67] vs. 66.38 years [7.66], P = 0.27) and durations of diabetes (median 53.00 years [interquartile range 51.00, 58.00] vs. 53.00 years [51.00, 57.00], P = 0.51). Canadians had higher HbA1c (mean 7.53% [SD 1.03] [59 mmol/mol] vs. 7.22% [0.98] [55 mmol/mol], P < 0.0001), lower QOL (36.9% vs. 48.7% with “excellent” QOL, P = 0.0002), and less CAD (29.7% vs. 41.2%, P = 0.0003) and insulin pump use (43.3% vs. 55.6%, P = 0.0002). Other complication rates were similar. Residual differences for Canadians compared with Americans remained after adjustment for age, sex, CAD, PAD, education, and relevant a priori selected variables: 0.28% higher HbA1c (P = 0.0004); and odds ratios of 0.68 (95% CI 0.51, 0.90), 0.46 (0.31, 0.68), and 0.71 (0.52, 0.96) for higher QOL, CAD, and insulin pump use, respectively. CONCLUSIONS Although Canadians and Americans have similar rates of complications other than CAD, further research is required to understand why Canadians have higher HbA1c levels, lower QOL, and less insulin pump use.

Association of Continuous Subcutaneous Insulin Injection Pumps with Lower HbA1c and Mortality in Type 1 Diabetes of Chronic Duration (1728-P)

SamenvattingContinuous subcutaneous insulin infusion pumps (CSII) may improve HbA1c and quality of life relative to the use of multiple daily injections (MDI) in individuals with type 1 diabetes (T1D), yet there is limited information about the relationship of CSII to mortality. The 50-Year Medalist Study provides a unique opportunity to investigate in 944 individuals with more than 50 y of T1D (mean duration = 53 y, HbA1c = 7.1%, age = 65 y, age at onset = 11 y, daily insulin dose = 0.43 u/kg; 59% use CSII, 49% for 10 y or longer).