Table_1_Lower insulin level is associated with sarcopenia in community-dwelling frail and non-frail older adults.pdf

BackgroundSarcopenia is common among older individuals with and without type 2 diabetes mellitus (T2DM). There are conflicting evidence in support of the role of insulin in the development of age-related and T2DM-related sarcopenia. We investigated the relationships between the levels of fasting insulin and other blood biomarkers related to insulin or lipid metabolism with the presence of sarcopenia in two independent studies.Materials and methodsIn 246 pre-frail frail older individuals with (n = 41) and without T2DM (n = 205) in the Singapore Frailty Interventional Trial, sarcopenia was defined by low appendicular lean mass (ALM) relative to total body mass (skeletal muscle index, SMI = ALM/height2) and low lower limb strength or gait speed according to the Asian Working Group for Sarcopenia (AWGS) criteria released in 2019, and related to levels of fasting insulin and glucose, C-peptide, IGF-1, leptin, and active ghrelin. This investigation was validated in another independent study sample of 189 robust and pre-frail frail elderly in the Singapore Longitudinal Aging Study Wave 2 (SLAS-2).ResultsCompared to non-sarcopenic individuals, those with sarcopenia and possible sarcopenia showed significantly lower fasting insulin (p ConclusionDysregulated insulin secretion in diabetic and non-diabetic older individuals may play an important role in age-related and diabetes-related sarcopenia.</p

Additional file 1 of Association of plasma angiogenin with risk of major cardiovascular events in type 2 diabetes

Supplementary Material 1: Supplementary Figures and Table

Plasma tryptophan- kynurenine pathway metabolites and risk for progression to end stage kidney disease in patients with type 2 diabetes

Objective: We sought to study the associations between plasma metabolites in tryptophan-kynurenine pathway and the risk of progression to end stage kidney disease (ESKD) in patients with type 2 diabetes. Design and Methods: Plasma tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid and xanthurenic acid concentrations were measured in discovery (N=1915) and replication (N=346) cohorts. External validation was performed in Chronic Renal Insufficiency Cohort (CRIC) participants with diabetes (N=1312). The primary outcome was a composite of incident ESKD (progression to eGFR < 15 ml/min/1.73m2, sustained dialysis or renal death). The secondary outcome was annual eGFR decline. Results: In discovery cohort, tryptophan was inversely associated with risk for ESKD and kynurenine-to-tryptophan ratio (KTR) was positively associated with risk for ESKD after adjustment for clinical risk factors including baseline eGFR and albuminuria (adjusted HR [95% CI], 0.62 [0.51-0.75] and 1.48 [1.20-1.84], per one SD). High levels of kynurenic acid and xanthurenic acid were associated with low risks of ESKD (0.74 [0.60-0.91] and 0.74 [0.60-0.91]). Consistently, high levels of tryptophan, kynurenic acid and xanthurenic acid were independently associated with a slower eGFR decline whilst a high KTR was predictive of a faster eGFR decline. Similar outcomes were obtained in replication cohort. Furthermore, the inverse association between kynurenic acid and risk of ESKD was externally validated in CRIC participants with diabetes (adjusted HR 0.78 [0.65-0.93]). Conclusion: Accelerated catabolism of tryptophan in kynurenine pathway may be involved in progressive loss of kidney function. However, shunting the kynurenine pathway toward kynurenic acid branch may potentially slow renal progression.</p