BACKGROUND. In the Joslin Medalist Study (Medalists), we determined whether significant associations exist between β cell function and pathology and clinical characteristics. METHODS. Individuals with type 1 diabetes (T1D) for 50 or more years underwent evaluation including HLA analysis, basal and longitudinal autoantibody (AAb) status, and β cell function by a mixed-meal tolerance test (MMTT) and a hyperglycemia/ arginine clamp procedure. Postmortem analysis of pancreases from 68 Medalists was performed. Monogenic diabetes genes were screened for the entire cohort. RESULTS. Of the 1019 Medalists, 32.4% retained detectable C-peptide levels (>0.05 ng/mL, median: 0.21 ng/mL). In those who underwent a MMTT (n = 516), 5.8% responded with a doubling of baseline C-peptide levels. Longitudinally (n = 181, median: 4 years), C-peptide levels increased in 12.2% (n = 22) and decreased in 37% (n = 67) of the Medalists. Among those with repeated MMTTs, 5.4% (3 of 56) and 16.1% (9 of 56) had waxing and waning responses, respectively. Thirty Medalists with baseline C-peptide levels of 0.1 ng/mL or higher underwent the clamp procedure, with HLA-/AAband HLA + /AAb-Medalists being most responsive. Postmortem examination of pancreases from 68 Medalists showed that all had scattered insulin-positive cells; 59 additionally had few insulin-positive cells within a few islets; and 14 additionally had lobes with multiple islets with numerous insulin-positive cells. Genetic analysis revealed that 280 Medalists (27.5%) had monogenic diabetes variants; in 80 (7.9%) of these Medalists, the variants were classified as "likely pathogenic" (rare exome variant ensemble learner [REVEL] >0.75). CONCLUSION. All Medalists retained insulin-positive β cells, with many responding to metabolic stimuli even after 50 years of T1D. The Medalists were heterogeneous with respect to β cell function, and many with HLA + diabetes risk alleles also had monogenic diabetes variants, indicating the importance of genetic testing for clinically diagnosed T1D.

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.

Aims Few data regarding prevalence of and risk factors for poor bone health in aging individuals with long-standing T1D are available. In this study we aim to describe the prevalence of bone fragility and to identify factors associated with low bone density in individuals with long term T1D. Methods We examined the prevalence of non-vertebral fractures in 985 subjects enrolled in the Joslin 50-Year Medalist Study, and measured bone mineral density (BMD) by dual-energy X-ray absorptiometry at the femoral neck, lumbar spine and radius in a subset (65 subjects, mean age 62.6 years, duration 52.5 years, HbA1c 7.1%) with no significant clinical or demographic differences from the rest of the cohort. Results Medalists have low prevalence of fractures (0.20% hip and 0.91% wrist) and normal Z-score values (spine +1.15, total hip +0.23, femoral neck −0.01, radius +0.26; p>0.05 for differences vs 0 at all sites). A significant relationship was found between lower BMD and higher total cholesterol, triglycerides and LDL levels, but not HbA1c. Low BMD at the femoral neck was associated with cardiovascular disease after adjustment for confounding factors: prevalence risk ratio (RR) [95% CI] of 4.6 [1.2–18.1], p=0.03 of CVD. No other diabetic vascular complication was found to be associated with low BMD. Conclusions These are the first data regarding bone health in aging individuals with T1D for more than 50 years. The low rates of non-vertebral fractures and the normal Z-score suggest the long T1D diabetes duration did not increase the risk of bone fractures in Medalists compared to non-diabetic peers. Additionally, the association with cardiovascular disease, demonstrates the BMD differences in group is likely not due to glycemic control alone.

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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BackgroundCardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes (T1D). A pro-calcific drift of circulating monocytes has been linked to vascular calcification and is marked by the surface expression of osteocalcin (OCN). We studied OCN+ monocytes in a unique population with ≥50 years of T1D, the 50-Year Joslin Medalists (J50M).MethodsCD45 bright/CD14+/OCN+ cells in the circulating mononuclear blood cell fraction were quantified by flow cytometry and reported as percentage of CD45 bright cells. Mechanisms were studied by inducing OCN expression in human monocytes in vitro.ResultsSubjects without history of CVD (n = 16) showed lower levels of OCN+ monocytes than subjects with CVD (n = 14) (13.1 ± 8.4% vs 19.9 ± 6.4%, p = 0.02). OCN+ monocytes level was inversely related to total high density lipoprotein (HDL) cholesterol levels (r = −0.424, p = 0.02), large (r = −0.413, p = 0.02) and intermediate (r = −0.445, p = 0.01) HDL sub-fractions, but not to small HDL. In vitro, incubation with OxLDL significantly increased the number of OCN+ monocytes (p < 0.01). This action of OxLDL was significantly reduced by the addition of HDL in a concentration dependent manner (p < 0.001). Inhibition of the scavenger receptor B1 reduced the effects of both OxLDL and HDL (p < 0.05).ConclusionsLow OCN+ monocytes levels are associated with lack of CVD in people with long duration T1D. A possible mechanism for the increased OCN+ monocytes could be the elevated levels of oxidized lipids due to diabetes which may be inhibited by HDL. These findings suggest that circulating OCN+ monocytes could be a marker for vascular disease in diabetic patients and possibly modified by HDL elevation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0599-2) contains supplementary material, which is available to authorized users.

Although Canadians and Americans have similar rates of complications other than CAD, further research is required to understand why Canadians have higher HbA levels, lower QOL, and less insulin pump use.

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