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Background Lifetime glycemic exposure and its relationship with age at diagnosis in type 2 diabetes (T2D) are unknown. Pharmacologic glycemic management strategies for young-onset T2D (age at diagnosis 3 times higher for young-onset versus usual-onset T2D (41.0 [95% confidence interval 39.1–42.8] versus 12.1 [11.8–12.3] A1C-years [1 A1C-year = 1 year with 8% average A1C]). Younger age at diagnosis was associated with faster glycemic deterioration (A1C slope over time +0.08% [0.078–0.084%] per year for age at diagnosis 20 years versus +0.02% [0.016–0.018%] per year for age at diagnosis 50 years; p-value for interaction, In a population-based cohort, Calvin Ke and colleagues investigate age at diagnosis and glycemic trajectories in Type 2 diabetes patients., Author summary Why was this study done? Young-onset type 2 diabetes (diagnosed before age 40 years) is an aggressive disease, associated with higher risks of mortality and other complications compared with usual-onset type 2 diabetes (diagnosed at age 40 years or after). Although exposure to hyperglycemia is a key risk factor for type 2 diabetes complications, the magnitude of this exposure over a lifetime has never been quantified. Because young people were excluded from randomized control trials of oral glucose-lowering drugs, it is unknown whether these drugs are effective for treating young-onset type 2 diabetes. What did the researchers do and find? Young-onset type 2 diabetes was associated with over triple the exposure to hyperglycemia from diagnosis until age 75 years compared with usual-onset type 2 diabetes. Diabetes progressed much faster in young-onset type 2 diabetes compared with usual-onset type 2 diabetes. Compared with usual-onset type 2 diabetes, people with young-onset type 2 diabetes had smaller responses to most metformin-based drug combinations and greater responses to other combinations containing sulfonylureas. What do these findings mean? Excess exposure to hyperglycemia and rapid disease progression in young-onset T2D call for better treatment strategies. The differential responses to oral glucose-lowering drugs between young- and usual-onset T2D suggest that better disease classification could guide personalized therapy.

Denice Feig and colleagues assess the association between gestational diabetes, gestational hypertension, and preeclampsia and the development of future diabetes in a database analysis of pregnant women in Ontario, Canada., Background Women with preeclampsia (PEC) and gestational hypertension (GH) exhibit insulin resistance during pregnancy, independent of obesity and glucose intolerance. Our aim was to determine whether women with PEC or GH during pregnancy have an increased risk of developing diabetes after pregnancy, and whether the presence of PEC/GH in addition to gestational diabetes (GDM) increases the risk of future (postpartum) diabetes. Methods and Findings We performed a population-based, retrospective cohort study for 1,010,068 pregnant women who delivered in Ontario, Canada between April 1994 and March 2008. Women were categorized as having PEC alone (n = 22,933), GH alone (n = 27,605), GDM alone (n = 30,852), GDM+PEC (n = 1,476), GDM+GH (n = 2,100), or none of these conditions (n = 925,102). Our main outcome was a new diagnosis of diabetes postpartum in the following years, up until March 2011, based on new records in the Ontario Diabetes Database. The incidence rate of diabetes per 1,000 person-years was 6.47 for women with PEC and 5.26 for GH compared with 2.81 in women with neither of these conditions. In the multivariable analysis, both PEC alone (hazard ratio [HR] = 2.08; 95% CI 1.97–2.19) and GH alone (HR = 1.95; 95% CI 1.83–2.07) were risk factors for subsequent diabetes. Women with GDM alone were at elevated risk of developing diabetes postpartum (HR = 12.77; 95% CI 12.44–13.10); however, the co–presence of PEC or GH in addition to GDM further elevated this risk (HR = 15.75; 95% CI 14.52–17.07, and HR = 18.49; 95% CI 17.12–19.96, respectively). Data on obesity were not available. Conclusions Women with PEC/GH have a 2-fold increased risk of developing diabetes when followed up to 16.5 years after pregnancy, even in the absence of GDM. The presence of PEC/GH in the setting of GDM also raised the risk of diabetes significantly beyond that seen with GDM alone. A history of PEC/GH during pregnancy should alert clinicians to the need for preventative counseling and more vigilant screening for diabetes. Please see later in the article for the Editors' Summary, Editors' Summary Background Diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin (a hormone that regulates blood sugar), known as type 1 diabetes, or when the body cannot effectively use the insulin it produces—type 2 diabetes. Raised blood sugar, is a common effect of uncontrolled diabetes and over time leads to serious complications and even death. Worryingly, the global burden of type 2 diabetes is increasing worldwide, and the World Health Organization estimates that 90% of the 347 million people with diabetes currently have type 2 diabetes. Previous studies have shown that type 2 diabetes can be prevented or delayed in high risk groups by a range of lifestyle and treatment interventions and so it is important to identify potential high risk groups to screen for type 2 diabetes. Why Was This Study Done? Gestational diabetes (a form of diabetes that is related to pregnancy) is a major risk factor for developing type 2 diabetes. Therefore, diabetes prevention strategies should target women with gestational diabetes. Likewise, other common disorders of pregnancy possibly associated with insulin resistance, such as preeclampsia (a condition in which affected women have high blood pressure, fluid retention, and protein in their urine) and gestational hypertension (high blood pressure associated with pregnancy), may lead to the future development of type 2 diabetes. So women with these conditions may also benefit from diabetes prevention strategies. Therefore, in this large database study from Ontario, Canada, the researchers examined whether pregnant women with preeclampsia or gestational hypertension had an increased risk of developing diabetes in the years following pregnancy even if they did not have gestational diabetes. What Did the Researchers Do and Find? The researchers used a comprehensive Canadian health database to identify all women age 15 to 50 years of age who delivered in an Ontario hospital between April 1994 and March 2008. They then identified women who had preeclampsia, gestational hypertension, or gestational diabetes through hospital records and outpatient information. The researchers then used records from the Ontario Diabetes Database to record whether these women went on to develop diabetes in the period from 180 days after delivery until March 2011. Using these methods, the researchers identified 1,010,068 pregnant women suitable for analysis, of whom 22,933 had only preeclampsia, 27,605 had only gestational hypertension, and 30,852 had only gestational diabetes: 2,100 women had both gestational diabetes and gestational hypertension and 1,476 women had gestational diabetes and preeclampsia. Overall, 35,077 women developed diabetes (3.5%) in the follow-up period (median of 8.5 years) at a median age of 37 years. In a modeling analysis, the researchers found that women with gestational diabetes had a 15-fold increased rate of developing diabetes compared to women without gestational diabetes, gestational hypertension, and preeclampsia, while women with gestational diabetes plus either preeclampsia or gestational hypertension had a 20- to 21-fold increased rate. These results were slightly reduced after adjusting for age, income quintile, hypertension prior to pregnancy, and co-morbidity, giving a hazard ratio (HR) of 1.95 for gestational hypertension alone, an HR of 2.08 for preeclampsia alone, an HR of 12.77 for gestational diabetes alone, an HR of 18.49 for gestational diabetes plus gestational hypertension and finally, an HR of 15.75 for gestational diabetes plus preeclampsia. These Findings Mean? These findings suggest that both preeclampsia and gestational hypertension without gestational diabetes are associated with a 2-fold increased incidence of diabetes in the years following pregnancy after controlling for several important variables. When combined with gestational diabetes, these conditions were associated with a further elevation in diabetes incidence additional to the 13-fold increased incidence resulting from gestational diabetes alone. A limitation of this study was the lack of information on obesity and body mass index, factors which are also associated with increased risk of developing diabetes. Nevertheless, these findings highlight a possible new risk factor for diabetes, and suggest that clinicians should be aware of the need for preventative measures and vigilant screening for diabetes in women with a history of preeclampsia or gestational hypertension. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001425. NHS Choices has information about preeclampsia, gestational diabetes, and gestational hypertension Living with diabetes is a useful resource for patients with diabetes The Preeclampsia Foundation has more information about preeclampsia