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Objective. To evaluate the prognostic value of glomerular hyperfiltration on long-term kidney-related outcomes and mortality in subjects with diabetes. Methods. We retrospectively analyzed 21-year longitudinal data from 314 patients with long-standing type 2 or type 1 diabetes. Glomerular hyperfiltration was identified based on the age- and sex-specific distribution of the glomerular filtration rate measured by 99mTc-DTPA dynamic renal scintigraphy (mGFR). The primary outcome was a composite of doubling of serum creatinine, end-stage kidney disease (ESKD), or cardiorenal death. The kidney-specific outcome was a composite of doubling of serum creatinine, ESKD, or renal death. Results. Over a median of 21.0 years, the primary composite outcome occurred in 25 (39.7%), 24 (38.1%), and 46 (24.5%) participants with high (H-mGFR, n=63), low (L-mGFR, n=63), or normal glomerular filtration (N-mGFR, n=188), respectively. Compared with N-mGFR, the hazard ratio [95% confidence interval] for the primary composite outcome was 2.09 [1.25–3.49] in H-mGFR and 1.81 [1.05–3.16] in L-mGFR. The hazard ratio for the kidney-specific composite outcome was 4.95 [2.21–11.09] in H-mGFR and 3.81 [1.70–8.56] in L-mGFR. The hazard ratios for doubling of serum creatinine and cardiorenal death were 4.86 [2.18–10.90] and 2.18 [1.24–3.83] in H-mGFR, respectively, and 4.04 [1.77–9.20] and 2.26 [1.27–4.01] in L-mGFR. Conclusions. Glomerular hyperfiltration, similar to hypofiltration, increases the combined risk of worsening kidney function and mortality from cardiovascular or renal causes in patients with diabetes. These findings encourage the active screening of these patients to optimize risk stratification and treatment of subclinical kidney disease.

Background: Abnormal circadian blood pressure (BP) patterns and reduced heart rate variability (HRV) are established risk factors for cardiovascular events in diabetic patients. However, studies assessing all-cause mortality associated with altered BP patterns and HRV in diabetes are limited by follow-up periods of less than 10 years. Methods: We examined a cohort of 349 patients with type 2 diabetes ( n =284) or type 1 diabetes ( n =65) recruited in Pisa (Italy) from 1999 and followed-up for 21 years, all with available 24-hour ambulatory BP and HRV monitoring. Dipping, non-dipping and reverse dipping status were defined as a ≥10% decline, Results: After 6,251 person-years of follow-up (median follow-up 21.0 [14.0-21.0] years, 183 [52%] women, age 57.1±11.9 y, BMI 29.4±5.9 kg/m 2 , HbA1c 8.6±2.1%), a total of 136 (39%) deaths occurred. Compared with dippers (n=166), non-dippers (n=144) and reverse dippers (n=39) showed progressively higher prevalence of cardiac autonomic neuropathy (11%, 16% and 31%, respectively), low HRV (45% vs 53% vs 62%), 24-hour hypertension (40%, 60% and 67%), isolated nocturnal hypertension (5%, 27% and 49%), postural hypotension (14%, 26% and 43%), and lower prevalence of white-coat hypertension (31%, 17% and 13%). Reverse dippers and non-dippers had progressively lower mean overall survival (OS) compared with dippers (16.1±5.3 years, 17.5±5.3 years and 18.6±4.6 years, respectively). Reverse dippers also showed an increased risk of all-cause mortality after adjustment for age, sex, BMI, office SBP, plasma glucose, and diabetes duration and type (HR 2.3 [1.4-3.8]). Patients with low HRV had reduced mean OS than those with high HRV (16.9±5.5 and 18.8±4.4, respectively) but similar adjusted risk (HR 1.3 [0.9-1.9]). No significant interactions emerged between BP patterns, HRV and diabetes type on OS. Conclusions: Non-dipping and reverse dipping BP patterns are associated with an increased prevalence of cardiac autonomic neuropathy and reduced survival probability in diabetic patients over a 21-year follow-up, with reverse dipping more than doubling the adjusted risk of all-cause mortality.