Albuminuria regression and all-cause mortality among insulin-treated patients with Type 2 diabetes: analysis of a large UK Primary Care cohort

Background: Overt albuminuria (urinary albumin-creatinine ratio (ACR) >300mg/g) is an established risk factor for progression of nephropathy and total mortality. However, whether, a reduction in ACR translates into a reduction in mortality and/or cardiovascular events among insulintreated patients with Type 2 diabetes (T2D) in routine practice is currently not known.Methods We obtained data on a large cohort of insulin users with T2D and nephropathy (baseline ACR ≥ 300mg/g) from UK general practices between 2007 and 2014. Their corresponding ACR values after one year of follow up were thereafter categorised into: (1) less than 300mg/g (i.e. albuminuria regression) or (2) >300mg/g (i.e. non-regression of albuminuria), and the cohort was followed up for 5 years for all-cause mortality and cardiovascular events. Cox proportional hazard models were fitted to estimate the risk of all-cause death.Results A total of 11,074 patients with insulin-treated T2D met the inclusion criteria. Their mean age was 62.3(13.6) years; mean HbA1c: 8.7(1.8) %; and 53% were male. 682 deaths occurred after a follow-up period of 43,393 person-years with a mortality rate of 16 per 1000 person-years. 5-year survival was markedly reduced in the group whose proteinuria persisted or progressed (91 vs 95%; log-rank p-value less than 0.001). Compared to patients whose ACR levels remained above 300mg/g, all-cause mortality and cardiovascular events were 31% and 27% lower in those whose albuminuria regressed to less than 300mg/g (aHR: 0.69; 95%CI: 0.52 to 0.91; p=0.008 and aHR: 0. 73; 95%CI: 0.54 to 0.98; p=0.041) respectively.Conclusion: In patients with insulin-treated T2D and nephropathy in routine practice, a regression in albuminuria (e.g. via better BP or glycaemic control) is associated with a significant reduction in all-cause mortality. Thus, albuminuria is not simply a risk marker of renal and cardiovascular disease, but also an independent target for therapy. Albuminuria reduction should be viewed as a goal for renal and cardiovascular protection

Individual and combined relationship between reduced eGFR and/or increased urinary albumin excretion rate with mortality risk among insulin treated patients with Type 2 diabetes in routine practice

Background: Low estimated glomerular filtration rate (eGFR) and increased urinary albumin-to-creatinine ratio (ACR) are well-recognised prognostic markers of cardiovascular (CV) risk, but their individual and combine relationship with CV disease and total mortality among insulin-treated Type 2 Diabetes (T2D) patients in routine clinical care is unclear. Methods: We analysed data for insulin users with T2D from UK general practices between 2007 and 2014 and examined the association between mortality rates and CKD [categorised by low eGFR ((less 60mL/min/1.73 m2); high eGFR (≥60mL/min/1.73 m2); low ACR (less 300mg/g); and high ACR (≥300mg/g) at insulin initiation] after a 5-year follow-up period using Cox proportional hazard models.Results: A total of 18,227 patients were identified (mean age: 61.5±13.8 years, mean HbA1c: 8.6±1.8%). After adjusting for confounders, when compared to adults on insulin therapy with an eGFR less 60 and an ACR ≥300 (low eGFR + high ACR) after a follow up period of 5 years, patients with an eGFR less 60 and an ACR less 300 (low eGFR + low ACR) had a 6% lower mortality rate (aHR: 0.94; 95%CI: 0.79 to1.12); those with an eGFR >60 and an ACR ≥300 (high eGFR + high ACR) had a 20% lower mortality rate (aHR: 0.80; 95%CI: 0.68 to 0.96); and those with an eGFR >60 and an ACR less 300 (high eGFR + low ACR) had the lowest death rate (28% less; aHR: 0.72; 95%CI: 0.59 to 0.87 ).Conclusion: This study shows that among a large cohort of insulin-treated T2D patients in routine practice, the combination of reduced eGFR with increased ACR was associated with the greatest risk of premature death, followed closely by those with reduced eGFR and normal ACR levels. Adoption of aggressive CV risk management strategies to reduce mortality in patients with a low eGFR and albuminuria is essential in these high risk patients with T2D

Comparison of cardiovascular and metabolic outcomes in people with type 2 diabetes on insulin versus non-insulin glucose-lowering therapies (GLTs): A systematic review and meta-analysis of clinical trials.

OBJECTIVES: To compare the cardiovascular and metabolic outcomes of Insulin versus non-insulin glucose lowering therapy (GLT). METHODS: We included randomised control trials (RCTs) which randomised patients aged >18years with Type 2 Diabetes (T2D) to insulin vs non-insulin GLT. We used risk ratios (RR), risk difference (RD) and odds ratios (OR) with 95% confidence interval (95%CI) to analyse the treatment effects of dichotomous outcomes and mean differences (with 95% CI) for continuous outcomes. RESULTS: We included 18 RCTs with 19,300 participants. There was no significant difference in the risk of all-cause mortality and CV events between the groups (RR=1.01; 95%CI: 0.96-1.06; p=0.69). In 16 trials, insulin showed greater efficacy in glycaemic control (mean diff=-0.20; 95%CI: -0.28 to -0.11) but the proportion achieving HbA1c level of either ⩽7.0% or 7.4% (53 or 57mmol/mol) was similar in both (OR=1.55; 95%CI=0.92-2.62). The non-insulin group had a significant reduction in weight (mean diff=-3.41; 95%CI: -4.50 to -2.32) and an increase in the proportion of adverse events (54.7% vs 45.3%, p=0.044), but the insulin group showed an (RR=1.90; 95%CI: 1.44-2.51) increased risk of hypoglycaemia. CONCLUSION: There was no difference in the risk of all-cause mortality and adverse cardiovascular (CV) events between Insulin and non-insulin GLTs. Insulin was associated with superior reduction in HbA1c; least reduction in weight and higher risk of hypoglycaemia. Both showed similar proportion of patients achieving HbA1c target. Non-insulin GLTs were associated with a higher risk in reported adverse drug events

Premixed vs basal-bolus insulin regimen in Type 2 diabetes: comparison of clinical outcomes from randomized controlled trials and real-world data.

AIM: To evaluate the concordance between data derived from randomized controlled trial (RCT) and real-world estimates of HbA1c and weight change after 24 weeks of initiation of a basal-bolus compared with a premixed insulin regimen in people with Type 2 diabetes. METHODS: Data eight RCTs were pooled after a systematic review of studies examining basal-bolus (n = 1893) or premixed (n = 1517) regimens. Real-world data were extracted from the UK primary care dataset for people on basal-bolus (n = 7483) or premixed insulin regimens (n=10 744). The mean differences between HbA1c and weight from baseline were calculated using t-tests, while analysis of variance was used to compare the two treatment regimens. Linear regression analyses were used to determine the predictors of this change. RESULTS: Both insulin regimens were associated with HbA1c reductions (real-world data -0.28%; RCT data, -1.4%) and weight gain (real-world data, +0.27 kg; RCT data, +2.96 kg) but there were no significant differences between basal-bolus and premixed insulin. Discordances in the pattern of treatment response were observed, however, between real-world and RCT data for both insulin regimens. For any given baseline HbA1c concentration, the change in HbA1c in the RCTs was greater than in real-world conditions and for those with baseline weight above ~60 kg, RCT data showed overall weight gain in contrast to slight weight loss in the real-world population. Lastly, for both randomized controlled trial and real-world populations, while greater baseline weight was associated with reduced response to treatment, the association was much steeper in the RCT than in the real-world population. In addition, greater baseline weight was associated with greater weight reductions in both premixed insulin and basal-bolus insulin regimens, although to a lesser extent with the latter. CONCLUSION: These results highlight specific discrepancies in the HbA1c reduction and weight change in insulin regimen between real world versus RCT populations; with greater reduction in HbA1c and greater increase in weight observed in the RCT population than in the real-world population. Also, the basal-bolus regimens in both real-world and RCT populations showed greater reduction in HbA1c compared to the premix regimen (though more marked in RCTs), while the premix regimen showed greater increase in weight in real-world, as against basal-bolus in the RCT population

Dissimilar impact of type 2 diabetes on cardiovascular outcomes according to age categories: a nationwide population study from Hungary

BACKGROUND: The excess risks of mortality and cardiovascular morbidity among patients with type 2 diabetes mellitus (T2DM) is well known. In this nationwide study, we assessed risks of mortality and cardiovascular events comparing patients with T2DM and matched controls. METHODS: We identified patients with T2DM in a retrospective cohort study using the database of the National Health Insurance Fund between 1 January 2010 and 31 December, 2013. Controls were randomly included and matched according to age, gender, and zip code of residence. Patients were divided into subgroups according to age decades for outcome analyses. RESULTS: During the mean follow-up period of 2.3 years, 152,678 patients with T2DM and 305,356 matched controls were included. Patients with T2DM showed significantly higher risk for all-cause mortality (HR 1.26, 95% CI 1.22-1.29, p < 0.0001), myocardial infarction (HR 1.81, 95% CI 1.69-1.94, p < 0.0001) and stroke (HR 1.40, 95% CI 1.35-1.46, p < 0.0001) compared to matched controls. The higher risk associated with T2DM for mortality, myocardial infarction and stroke differed significantly between age groups (pinteraction < 0.05 for all outcomes) with significantly higher risk observed in younger patients. CONCLUSIONS: The risk of cardiovascular outcomes and all-cause mortality is significantly higher in patients with T2DM. Notably, the relative hazard increases with decreasing age suggesting that younger patients with T2DM should receive more attention for cardiovascular prevention