PracticeUpdate Diabetes June 2019

EDITOR’S PICKS 9

Diuretics May Increase Risk of Lower Limb Events in Type 2 Diabetes Take-home message • These authors used data from the SURDIAGENE prospective observational cohort study (n=1459) to inves- tigate whether diuretic use increased the risk of lower limb amputation (LLA) in people with type 2 diabetes. After comparing LLA risk in patients with and without diuretic treatment over a 7.1-year follow-up, the authors determined that the incidence of lower limb events (LLE) was 1.80 per 100 patient-years in diuretic users compared with 1.00 in non-users. The hazard ratio for LLE in diuretic users versus non-users was 2.08, which was significant even after multivariable adjustments. • Based on the results of this trial, the authors suggest that diuretic use increases the risk of LLE including LLA in patients with type 2 diabetes. This may help explain the increased risk of LLA in people with type 2 diabetes who use an SGLT2 inhibitor like canagliflozin. Clinicians should emphasize the importance of hydration in patients treated with SGLT2 inhibitors. Jason Sloane MD Abstract AIMS/HYPOTHESIS Recently, safety data signalled an increased risk of amputations in people taking canagliflozin, a sodium-glucose cotrans- porter 2 (SGLT2) inhibitor. If this side effect is due to drug-induced hypovolaemia, diuretics should also increase that risk. The aim of this study was to analyse the association between diuretic use and the risk of lower limb events (LLEs) in people with type 2 diabetes. METHODS SURDIAGENE (SUivi Rénal, DIAbète de type 2 et GENEti- que) is a prospective observational cohort that includes people with type 2 diabetes enrolled from 2002 to 2012 and followed-up until onset of LLE, death or 31 December 2015, whichever came first. Pri- mary outcome was the first occurrence of LLE, a composite of lower limb amputation (LLA) and lower limb revascularisation (LLR). The rates of primary outcome were compared between participants taking and not taking diuretics at baseline in a Cox-adjusted model. RESULTS At baseline, of the 1459 participants included, 670 were tak- ing diuretics. In participants with and without diuretics, the mean ages were 67.1 and 62.9 years and 55.8% and 59.8% were men, respectively. During a median follow-up of 7.1 years, the incidence of LLE was 1.80 per 100 patient-years in diuretic users vs 1.00 in non-users (p<0.001). The HR for LLE in users vs non-users was 2.08 (95% CI 1.49, 2.93), p <0.001. This association remained significant in a multivariable-ad- justed model (1.49 [1.01, 2.19]; p=0.04) and similar after considering death as a competing risk (subhazard ratio 1.89 [1.35, 2.64]; p<0.001). When separated, LLA but not LLR, was associated with the use of diuretics: 2.01 (1.14, 3.54), p=0.02 and 1.05 (0.67, 1.64), p=0.84, respec- tively, in the multivariable-adjusted model. CONCLUSIONS/INTERPRETATION Among people with type 2 diabetes treated with diuretics, there was a significant increase in the risk of LLE, predominantly in the risk of LLA. Lower Limb Events in Individuals With Type 2 Diabetes: Evidence for an Increased Risk Associated With Diuretic Use. Diabetologia 2019 Feb 26;[EPub Ahead of Print], L Potier, R Roussel, G Velho, et al. www.practiceupdate.com/c/81051 Diabetologia

Abstract OBJECTIVE To investigate if early electronic identification and bedside management of inpatients with diabetes improves glycemic control in noncritical care. RESEARCH DESIGN AND METHODS We investigated a proactive or early inter- vention model of care (whereby an inpatient diabetes team electronically identified individuals with diabetes and aimed to provide bedside manage- ment within 24 h of admission) compared with usual care (a referral-based consultation service). We conducted a cluster randomized trial on eight wards, consisting of a 10-week baseline period (all clusters received usual care) followed by a 12-week active period (clusters randomized to early intervention or usual care). Outcomes were adverse glycemic days (AGDs) (patient-days with glucose <4 or >15 mmol/L [<72 or >270 mg/dL]) and adverse patient outcomes. RESULTS We included 1,002 consecutive adult inpatients with diabetes or new hyperglycemia. More patients received specialist diabetes manage- ment (92% vs. 15%, P < 0.001) and new insulin treatment (57% vs. 34%, P = 0.001) with early intervention. At the cluster level, incidence of AGDs decreased by 24% from 243 to 186 per 1,000 patient-days in the interven- tion arm (P < 0.001), with no change in the control arm. At the individual level, adjusted number of AGDs per person decreased from a mean 1.4 (SD 1.6) to 1.0 (0.9) days (-28% change [95% CI -45 to -11%], P = 0.001) in the intervention arm but did not change in the control arm (1.8 [2.0] to 1.5 [1.8], -9% change [-25 to 6%], P = 0.23). Early intervention reduced overt hyperglycemia (55% decrease in patient-days with mean glucose >15 mmol/L, P < 0.001) and hospital-acquired infections (odds ratio 0.20 [95% CI 0.07-0.58], P = 0.003). CONCLUSIONS Early identification and management of inpatients with dia- betes decreased hyperglycemia and hospital-acquired infections. Early Intervention for Diabetes in Medical and Surgical Inpatients Decreases Hyperglycemia and Hospital-Acquired Infections: A Clus- ter Randomized Trial. Diabetes Care 2019 Mar 28;[EPub Ahead of Print], M Kyi, PG Colman, PR Wraight, et al. www.practiceupdate.com/c/81683

VOL. 3 • NO. 2 • 2019