Not all patients with type 2 diabetes develop renal dysfunction. Identifying those at risk is problematic because even microalbuminuria, often used clinically as an indicator of future renal dysfunction, does not always precede worsening renal function. We sought to identify clinical risk factors at diagnosis of type 2 diabetes associated with later development of renal dysfunction. Of 5,102 U.K. Prospective Diabetes Study (UKPDS) participants, prospective analyses were undertaken in those without albuminuria (n ‫؍‬ 4,031) or with normal plasma creatinine (n ‫؍‬ 5,032) at diagnosis. Stepwise proportional hazards multivariate regression was used to assess association of putative baseline risk factors with subsequent development of albuminuria (microalbuminuria or macroalbuminuria) or renal impairment (Cockcroft-Gault estimated creatinine clearance <60 ml/min or doubling of plasma creatinine). Over a median of 15 years of follow-up 1,544 (38%) of 4,031 patients developed albuminuria and 1,449 (29%) of 5,032 developed renal impairment. Of 4,006 patients with the requisite data for both outcomes, 1,534 (38%) developed albuminuria and 1,132 (28%) developed renal impairment. Of the latter, 575 (51%) did not have preceding albuminuria. Development of albuminuria or renal impairment was independently associated with increased baseline systolic blood pressure, urinary albumin, plasma creatinine, and Indian-Asian ethnicity. Additional independent risk factors for albuminuria were male sex, increased waist circumference, plasma triglycerides, LDL cholesterol, HbA 1c (A1C), increased white cell count, ever having smoked, and previous retinopathy. Additional independent risk factors for renal impairment were female sex, decreased waist circumference, age, increased insulin sensitivity, and previous sensory neuropathy. Over a median of 15 years from diagnosis of type 2 diabetes, nearly 40% of UKPDS patients developed albuminuria and nearly 30% developed renal impairment. Distinct sets of risk factors are associated with the development of these two outcomes, consistent with the concept that they are not linked inexorably in type 2 diabetes.

Aims/hypothesis Women who develop gestational diabetes mellitus (GDM) have an elevated lifetime risk of type 2 diabetes mellitus. Recently, a series of studies has suggested that women with GDM also have an increased risk of cardiovascular disease (CVD). However, it is unclear if this risk is dependent upon the intercurrent development of type 2 diabetes. Thus, we conducted a systematic review and meta-analysis to evaluate the impact of GDM on future risk of incident CVD and to ascertain the role of type 2 diabetes in this regard. Methods We systematically searched the PubMed and EMBASE databases for observational studies that evaluated the association of GDM with subsequent CVD, with publication between 1 January 1950 and 30 August 2018. Two independent reviewers extracted data and the analysis was performed in accordance with Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. RRs were calculated using a random-effects model to assess the predictive value of GDM for future cardiovascular events. To evaluate whether incident type 2 diabetes in the GDM population influenced the association with CVD, we used meta-regression models followed by sensitivity analyses restricted to women who did not develop type 2 diabetes during follow-up. Results A pooled analysis of nine studies yielded data from 5,390,591 women (101,424 cardiovascular events). Compared with those who did not have GDM, women with GDM had a twofold higher risk of future cardiovascular events (RR 1.98 [95% CI 1.57, 2.50]). Meta-regression analysis showed that the rates of incident type 2 diabetes across the studies did not affect this risk (p = 0.34). Moreover, when restricted to women who did not develop type 2 diabetes, GDM remained associated with a 56% higher risk of future cardiovascular events (RR 1.56 [95% CI 1.04, 2.32]). GDM conferred a 2.3-fold increased risk of cardiovascular events in the first decade postpartum (RR 2.31 [95% CI 1.57, 3.39]). Conclusions/interpretation The diagnosis of GDM identifies young women who have a twofold higher risk of cardiovascular events postpartum compared with their peers. This risk is not dependent upon intercurrent type 2 diabetes and is apparent within the first decade after pregnancy. Thus, even without progressing to type 2 diabetes, women with GDM comprise an at-risk population for CVD and hence a potential opportunity for early risk factor surveillance and risk modification.