ObjectiveDiabetic retinopathy in type 2 diabetes is preceded by retinal nerve fiber layer (RNFL) thinning, an index of neurodegeneration. We investigated whether glucose metabolism status (GMS), measures of glycemia, and daily glucose variability (GV) are associated with RNFL thickness over the entire range of glucose tolerance.Research design and methods We used cross-sectional data from The Maastricht Study (up to 5,455 participants, 48.9% men, mean age 59.5 years and 22.7% with type 2 diabetes) to investigate the associations of GMS, measures of glycemia (fasting plasma glucose [FPG], 2-hour post-load glucose [2-h PG], HbA1c, advanced glycation endproducts [AGEs] assessed as skin autofluorescence [SAF]) and indices of daily GV (incremental glucose peak [IGP] and continuous glucose monitoring [CGM]-assessed standard deviation [SD]) with mean RNFL thickness. We used linear regression analyses and, for GMS, P for trend analyses. We adjusted associations for demographic, cardiovascular risk and lifestyle factors, and, only for measures of GV, for indices of mean glycemia. Results After full adjustment, type 2 diabetes and prediabetes (versus normal glucose metabolism) were associated with lower RNFL thickness (standardized beta [95%CI], respectively -0.16[-0.25;-0.08]; -0.05[-0.13;0.03]; Ptrend=0.001). Greater FPG, 2-h PG, HbA1c, SAF, IGP and CGM-assessed SD were also associated with lower RNFL thickness (per SD, respectively -0.05 [-0.08; -0.01]; -0.06 [-0.09; -0.02]; -0.05 [-0.08; -0.02]; -0.04 [-0.07; -0.01]; -0.06 [-0.12; -0.01]; and -0.07 [-0.21; 0.07]).Conclusion In this population-based study, a more adverse GMS and, over the entire range of glucose tolerance, greater glycemia and daily GV were associated with lower RNFL thickness. Hence, early identification of individuals with hyperglycemia, early glucose-lowering treatment, and early monitoring of daily GV may contribute to the prevention of RNFL thinning, an index of neurodegeneration and precursor of diabetic retinopathy.

Objective We investigated, using population-based data, whether worse autonomic function, estimated from lower 24-hour heart rate variability (HRV), was associated with beta cell function, assessed from beta cell response during an oral glucose tolerance test (OGTT). Research design and methods We used cross-sectional data from The Maastricht Study, a population-based cohort study (N = 2,007; age, mean ± SD:60 ± 8 years; 52% men; and 24% with type 2 diabetes). We used linear regression analyses with adjustment for potential confounders (demographic, cardiovascular, and lifestyle factors) to study the associations of time- and frequency-domain HRV (composite scores) with overall beta cell response (estimated from a composite score calculated from: C-peptidogenic index, overall insulin secretion, beta cell glucose sensitivity, beta cell potentiation factor, and beta cell rate sensitivity). In addition, we tested for interaction by sex and glucose metabolism status. Results After full adjustment, lower time- and frequency-domain HRV was significantly associated with lower overall beta cell response composite score (standardized beta, -0.055 [-0.098; -0.011] and − 0.051 [-0.095; -0.007], respectively). These associations were not modified by sex and there was no consistent pattern of interaction by glucose metabolism status. Conclusion The present etiological study found that worse autonomic function, estimated from lower HRV, was associated with worse beta cell function, estimated from a composite score in a population-based sample which covered the entire spectrum of glucose metabolism. Hence, autonomic dysfunction may contribute to beta cell dysfunction and, ultimately, to the alteration of glucose metabolism status from normal glucose metabolism to prediabetes and type 2 diabetes.

Objective We investigated, using population-based data, whether worse autonomic function, estimated from lower 24-hour heart rate variability (HRV), was associated with beta cell function, assessed from beta cell response during an oral glucose tolerance test (OGTT). Research design and Methods We used cross-sectional data from The Maastricht Study, a population-based cohort study (N=2,007; age, mean ± SD:60 ± 8 years; 52% men; and 24% with type 2 diabetes). We used linear regression analyses with adjustment for potential confounders (demographic, cardiovascular, and lifestyle factors) to study the associations of time- and frequency-domain HRV (composite scores) with overall beta cell response (estimated from a composite score calculated from: C-peptidogenic index, overall insulin secretion, beta cell glucose sensitivity, beta cell potentiation factor, and beta cell rate sensitivity). In addition, we tested for interaction by sex and glucose metabolism status. Results After full adjustment, lower time- and frequency-domain HRV was significantly associated with lower overall beta cell response composite score (standardized beta, -0.055 [-0.098; -0.011] and -0.051 [-0.095; -0.007], respectively). These associations were not modified by sex and there was no consistent pattern of interaction by glucose metabolism status. Conclusion The present study found that worse autonomic function, estimated from lower HRV, was associated with worse beta cell function, estimated from a composite score in a population-based sample which covered the entire spectrum of glucose metabolism. Hence, autonomic dysfunction may contribute to beta cell dysfunction and, ultimately, to the alteration of glucose metabolism status from normal glucose metabolism to prediabetes and type 2 diabetes.