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ObjectiveTo evaluate associations between gestational diabetes mellitus (GDM) and various incident cardiovascular disease (CVD) end points, considering the effects of the mediating role of type 2 diabetes and shared environmental/familial factors.Research design and methodsThis population-based cohort study included 10,02,486 parous women in Denmark during 1978-2016. We used Cox regression to 1) examine the associations of GDM with overall and type-specific CVDs using full-cohort and sibling-matched analysis, 2) quantify the impact of type 2 diabetes after GDM using mediation analysis, and 3) assess whether these associations were modified by prepregnancy obesity or maternal history of CVD.ResultsWomen with a history of GDM had a 40% increased overall CVD risk (hazard ratio [HR] 1.40, 95% CI 1.35-1.45). Sibling-matched analyses yielded similar results (HR 1.44, 95% CI 1.28-1.62). The proportion of association between GDM and overall CVD explained by subsequent type 2 diabetes was 23.3% (15.4-32.8%). We observed increased risks of specific CVDs, including 65% increased stroke risk and more than twofold risks for myocardial infarction, heart failure, and peripheral artery disease. The elevated overall risks were more pronounced among women with GDM and prepregnancy obesity or maternal history of CVD.ConclusionsA history of GDM was associated with increased risks of overall and specific CVDs. Increased risks were partly explained by subsequent type 2 diabetes, and the need to identify other pathways remains important. Continuous monitoring of women with a history of GDM, especially those with prepregnancy obesity or maternal history of CVD, may provide better opportunities to reduce their cardiovascular risk.

OBJECTIVE: To examine trends in peripheral artery disease (PAD), lower-extremity (LE) revascularization, and LE amputation in patients with incident type 2 diabetes. RESEARCH DESIGN AND METHODS: This cohort study included patients in Denmark diagnosed with type 2 diabetes in 1996–2015 and followed until 2020. Patients were age and sex matched with as many as three general population individuals. Outcomes comprised 5-year cumulative incidences of first-time PAD, LE revascularization, and LE amputation. Age- and sex-adjusted hazard ratios (aHRs) were computed using Cox regression. RESULTS: The cohort comprised 349,454 patients with incident type 2 diabetes (53% male; median age 62 years) and 1,025,054 general population individuals. Among patients with diabetes, decreases in 5-year cumulative incidence of PAD (from 6.2 to 3.4%; aHR 0.55 [95% CI 0.52–0.57]), LE revascularization (from 0.8 to 0.6%; aHR 0.80 [95% CI 0.71–0.90]), and LE amputation (from 1.0 to 0.4%; aHR 0.45 [95% CI 0.40–0.51]) occurred from 1996–2000 to 2011–2015. LE amputation decreased at all amputation levels (hip/thigh, knee/lower leg, and ankle/foot/toe) during the study period. In the general population, 5-year cumulative incidence remained stable (1.2–1.5% for PAD, ∼0.4% for LE revascularization, and ∼0.2% for LE amputation). However, the relative rates of all outcomes were two- to threefold higher in patients with diabetes than matched individuals in 2011–2015. CONCLUSIONS: In recent decades, the cumulative incidence of LE complications substantially decreased in patients with incident type 2 diabetes while remaining stable in the general population. [ABSTRACT FROM AUTHOR]

Objective: To evaluate associations between gestational diabetes mellitus (GDM) and various incident cardiovascular disease (CVD) end points, considering the effects of the mediating role of type 2 diabetes and shared environmental/familial factors.Research Design and Methods: This population-based cohort study included 10,02,486 parous women in Denmark during 1978-2016. We used Cox regression to 1) examine the associations of GDM with overall and type-specific CVDs using full-cohort and sibling-matched analysis, 2) quantify the impact of type 2 diabetes after GDM using mediation analysis, and 3) assess whether these associations were modified by prepregnancy obesity or maternal history of CVD.Results: Women with a history of GDM had a 40% increased overall CVD risk (hazard ratio [HR] 1.40, 95% CI 1.35-1.45). Sibling-matched analyses yielded similar results (HR 1.44, 95% CI 1.28-1.62). The proportion of association between GDM and overall CVD explained by subsequent type 2 diabetes was 23.3% (15.4-32.8%). We observed increased risks of specific CVDs, including 65% increased stroke risk and more than twofold risks for myocardial infarction, heart failure, and peripheral artery disease. The elevated overall risks were more pronounced among women with GDM and prepregnancy obesity or maternal history of CVD.Conclusions: A history of GDM was associated with increased risks of overall and specific CVDs. Increased risks were partly explained by subsequent type 2 diabetes, and the need to identify other pathways remains important. Continuous monitoring of women with a history of GDM, especially those with prepregnancy obesity or maternal history of CVD, may provide better opportunities to reduce their cardiovascular risk. [ABSTRACT FROM AUTHOR]

The article presents an analysis for Trends in HbA1c and LDL Cholesterol in Patients With Type 2 Diabetes Receiving First-Time Treatment in Northern Denmark, 2000–2017. Topics discussed include using laboratory and health care databases covering the entire population of Northern Denmark; generalizability of clinical trials to contemporary populations; and pretreatment HbA1c categories had increasingly large post treatment reductions.

OBJECTIVE To investigate whether the use of incretin-based drugs (GLP-1 receptor agonists, and dipeptidyl peptidase 4 [DPP4] inhibitors) is associated with acute pancreatitis. RESEARCH DESIGN AND METHODS The study was a nationwide population-based case-control study using medical databases in Denmark. Participants were 12,868 patients with a first-time hospitalization for acute pancreatitis between 2005 and 2012 and a population of 128,680 matched control subjects. The main outcome measure was the odds ratio (OR) for acute pancreatitis associated with different antihyperglycemic drugs. We adjusted for history of gallstones, alcoholism, obesity, and other pancreatitis-associated comorbidities and medications. RESULTS A total of 89 pancreatitis patients (0.69%) and 684 control subjects (0.53%) were ever users of incretins. The crude OR for acute pancreatitis among incretin users was 1.36 (95% CI 1.08-1.69), while it was 1.44 (95% CI 1.34-1.54) among users of other antihyperglycemic drugs. After confounder adjustment, the risk of acute pancreatitis was not increased among incretin users (OR 0.95 [95% CI 0.75-1.21]), including DPP4 inhibitor users (OR 1.04 [95% CI 0.80-1.37]) or GLP-1 receptor agonist users (OR 0.82 [95% CI 0.54-1.23]), or among nonincretin antihyperglycemic drug users (OR 1.05 [95% CI 0.98-1.13]), compared with nonusers of any antihyperglycemic drugs. Findings were similar in current versus ever drug users, and in patients with pancreatitis risk factors. The adjusted OR comparing incretin-based therapy with other antihyperglycemic therapy internally while also adjusting for diabetes duration and complications was 0.97 (95% CI 0.76-1.23). CONCLUSIONS Our findings suggest that the use of incretin-based drugs appears not to be associated with an increased risk of acute pancreatitis. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To assess the association between first-trimester HbA1c (A1C) and the risk of adverse pregnancy outcomes in type 1 diabetic pregnancies. RESEARCH DESIGN AND METHODS -- We identified all pregnant diabetic women in a Danish county from 1985 to 2003. A1C values from first trimester were collected, and pregnancy outcome was dichotomized as good (i.e., babies surviving the 1st month of life without major congenital abnormalities) and adverse (i.e., spontaneous and therapeutic abortion, stillbirth, neonatal death, or major congenital abnormalities detected within the 1st month). The prevalence of adverse outcomes was calculated according to quintiles of A1C. We computed receiver operating characteristic and lowess curve estimates and fitted logistic regression models to calculate prevalence odds ratio while adjusting for confounding by White class and smoking status. RESULTS -- Of 573 pregnancies, 165 (29%) terminated with adverse outcomes. The prevalence of adverse outcomes varied sixfold from 12% (95% CI 7.2-17) in the lowest to 79% (60-91) in the highest quintile of A1C exposure. From A1C levels >7%, we found an almost linear association between A1C and risk of adverse outcome, whereby a 1% increase in A1C corresponded to 5.5% (3.8-7.3) increased risk of adverse outcome. CONCLUSIONS -- Starting from a first-trimester A1C level slightly <7%, there is a dose-dependent association between A1C and the risk of adverse pregnancy outcome without indication of a plateau, below which the association no longer exits. A1C, however, seems to be of limited value in predicting outcome in the individual pregnancy. [ABSTRACT FROM AUTHOR]