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.
Summary Background Combination treatment with a glucagon-like peptide-1 (GLP-1) agonist and basal insulin has been proposed as a treatment strategy for type 2 diabetes that could provide robust ...glucose-lowering capability with low risk of hypoglycaemia or weight gain. We thus did a systematic review and meta-analysis of randomised controlled trials to assess the effect of this combination treatment on glycaemic control, hypoglycaemia, and weight gain in patients with type 2 diabetes. Methods We systematically searched PubMed, Embase, Cochrane, Web of Knowledge, FDA.gov , and ClinicalTrials.gov for randomised controlled trials (published between Jan 1, 1950, and July 29, 2014; no language restrictions) comparing GLP-1 agonist and basal insulin combination treatment to other anti-diabetic treatments. Our main endpoints were glycaemic control, hypoglycaemia, and change in weight. We assessed pooled data by use of a random-effects model. Findings Of 2905 identified studies, 15 were eligible and were included in our analysis (N=4348 participants). Compared with other anti-diabetic treatments, GLP-1 agonist and basal insulin combination treatment yielded an improved mean reduction in glycated haemoglobin (HbA1c ) of −0·44% (95% CI −0·60 to −0·29), an improved likelihood of achieving the target HbA1c of 7·0% or lower (relative risk RR 1·92; 95% CI 1·43 to 2·56), no increased relative risk of hypoglycaemia (0·99; 0·76 to 1·29), and a mean reduction in weight of −3·22 kg (−4·90 to −1·54). Furthermore, compared with basal-bolus insulin regimens, the combination treatment yielded a mean reduction in HbA1c of −0·1% (−0·17 to −0·02), with lower relative risk of hypoglycaemia (0·67, 0·56 to 0·80), and reduction in mean weight (−5·66 kg; −9·8 to −1·51). Interpretation GLP-1 agonist and basal insulin combination treatment can enable achievement of the ideal trifecta in diabetic treatment: robust glycaemic control with no increased hypoglycaemia or weight gain. This combination is thus a potential therapeutic strategy that could improve the management of patients with type 2 diabetes. Funding None.
It has long been recognized that the diagnosis of gestational diabetes mellitus (GDM) identifies a population of young women at high risk of developing Type 2 diabetes (T2DM) in the future. In recent ...years, however, a series of studies have revealed that antepartum glucose tolerance screening, a standard element of current obstetrical care instituted for the purpose of detecting GDM, may provide previously-unrecognized insight into a woman's future risk of metabolic and vascular disease. Indeed, it has emerged that in fact any degree of abnormal glucose tolerance detected on antepartum screening (i.e. not just GDM) predicts an increased future risk of pre-diabetes and diabetes, one that is proportional to the severity of dysglycemia observed in pregnancy. In addition, in the years following the index pregnancy, women with a history of GDM exhibit an enhanced cardiovascular risk profile and ultimately an increased incidence of cardiovascular disease (CVD), risks that may similarly extend to women with milder gestational glucose intolerance as well. Thus, by providing a unique window to a woman's risk potential for future metabolic and vascular disease, glucose tolerance testing in pregnancy, as currently practiced, may offer an opportunity for the early identification of high-risk individuals prior to the onset of clinical disease. Ultimately, the insight so derived may inform strategies for postpartum surveillance, risk factor modification, and disease prevention that may eventually lead to a reduction in the burden of T2DM and CVD in women.
Purpose of review
We aim to evaluate whether the current literature supports (i) a causal relationship between neighbourhood walkability and risk of diabetes or instead (ii) a strictly epidemiologic ...association.
Recent findings
Both cross-sectional and longitudinal studies have reported that neighbourhoods that are scored as having higher levels of walkability have lower rates of prevalent and incident diabetes, respectively. However, other studies have been inconclusive, with more nuanced findings suggesting that this association may be limited to particular demographic groups defined by age and socio-economics. Key factors limiting this literature include disparities in the measurement of walkability, the necessary reliance on observational study designs (recognizing the infeasibility of randomized controlled trials for addressing this question), and the difficulty of disentangling the potential concomitant effects of other components of the built environment.
Summary
At this time, causality cannot be ascertained in the relationship between neighbourhood walkability and risk of diabetes.
Studies have shown that, when implemented early in the course of type 2 diabetes mellitus, treatment with intensive insulin therapy for 2-3 weeks can induce a glycaemic remission, wherein patients ...are able to maintain normoglycaemia without any anti-diabetic medication. We thus did a systematic review and meta-analysis of interventional studies to assess the effect of short-term intensive insulin therapy on the pathophysiological defects underlying type 2 diabetes mellitus (pancreatic β-cell dysfunction and insulin resistance) and identify clinical predictors of remission.
We identified studies published between 1950 and Nov 19, 2012, which assessed the effect of intensive insulin therapy on β-cell function or insulin resistance, or both, or assessed long-term drug-free glycaemic remission in adults aged 18 years or older with newly diagnosed type 2 diabetes mellitus. We calculated pooled estimates by random-effects model. This study is registered with International Prospective Register of Systematic Reviews, number CRD42012002829.
We identified 1645 studies of which seven fulfilled inclusion criteria (n=839 participants). Five studies were non-randomised. A pooled analysis of the seven studies showed a post-intensive insulin therapy increase in Homeostasis Model Assessment of β-cell function as compared with baseline (1·13, 95% CI 1·02 to 1·25) and a decrease in Homeostasis Model Assessment of Insulin Resistance (-0·57, -0·84 to -0·29). In the four studies that assessed glycaemic remission (n=559 participants), the proportion of participants in drug-free remission was about 66·2% (292 of 441 patients) after 3 months of follow-up, about 58·9% (222 of 377 patients) after 6 months, about 46·3% (229 of 495 patients) after 12 months, and about 42·1% (53 of 126 patients) after 24 months. Patients who achieved remission had higher body-mass index than those who did not achieve remission (1·06 kg/m(2), 95% CI 0·55 to 1·58) and lower fasting plasma glucose (-0·59 mmol/L, 95% CI -1·11 to -0·07) at baseline.
Short-term intensive insulin therapy can improve the underlying pathophysiology in early type 2 diabetes mellitus, and thus might provide a treatment strategy for modifying the natural history of diabetes.
None.
Gestational diabetes mellitus (GDM) has historically been perceived as a medical complication of pregnancy that also serves as a harbinger of maternal risk of developing type 2 diabetes mellitus ...(T2DM) in the future. In recent decades, a growing body of evidence has detailed additional lifelong implications that extend beyond T2DM, including an elevated risk of ultimately developing cardiovascular disease. Furthermore, the risk factors that mediate this lifetime cardiovascular risk are evident not only after delivery but are present even before the pregnancy in which GDM is first diagnosed. The concept thus emerging from these data is that the diagnosis of GDM enables the identification of women who are already on an enhanced track of cardiometabolic risk that starts early in life. Studies of the offspring of pregnancies complicated by diabetes now suggest that the earliest underpinnings of this cardiometabolic risk profile may be determined in utero and may first manifest clinically in childhood. Accordingly, from this perspective, GDM is now seen as a chronic metabolic disorder that holds implications across the life span of both mother and child.
The discovery of insulin in 1921 and the progress achieved in the ensuing century highlight the promise and challenge of biochemically modifying the molecule to achieve optimization of its delivery ...and therapeutic efficacy. Normal endogenous insulin secretion consists of a highly orchestrated physiologic loop wherein multiple metabolic signals trigger the pancreatic β cells to secrete the precise amount of insulin into the portal system required to maintain euglycemia. Accordingly, in the treatment of diabetes, attempting to replicate this complex physiology with exogenous insulin therapy given subcutaneously presents a clinical challenge. In this context, recombinant DNA-based technology has enabled the development of insulin analogs that have been specifically designed to confer advantageous pharmacodynamic features that can better mimic endogenous insulin secretion. In this review, we discuss the development of the most widely available insulin preparations and provide evidence-based insight into their use in clinical practice.
Gestational diabetes mellitus (GDM), which has traditionally been defined as glucose intolerance of varying severity with first onset in pregnancy, is rising in prevalence with maternal hyperglycemia ...currently affecting one in every six pregnancies worldwide. Although often perceived as a medical complication of pregnancy, GDM is actually a chronic cardiometabolic disorder that identifies women who have an elevated lifetime risk of ultimately developing type 2 diabetes and cardiovascular disease. In identifying high-risk women early in the natural history of these conditions, the diagnosis of GDM raises the tantalizing possibility of early intervention and risk modification. However, before such promise can be realized in practice, a series of clinical challenges/obstacles (reviewed herein) must be overcome. Ultimately, the coupling of this life course perspective of GDM with concerted efforts to overcome these challenges may enable fulfilment of this unique opportunity for the primary prevention of diabetes and heart disease in women.
Background Women with gestational diabetes (GDM) have an elevated lifetime incidence of cardiovascular disease (CVD), but the basis of this excess risk remains to be established. In this context, we ...hypothesized that chronic exposure to adverse cardiovascular risk factors may contribute to their elevated risk of CVD. We thus sought to quantify the determinants of CVD risk in women with a history of GDM by performing mediation analyses. Methods Women in Ontario, Canada, with a live-birth pregnancy between Jan 1998 and Dec 2017 (n=757,541) were followed for a median of 13.2 years and stratified into the following 4 groups: women with GDM who developed CVD (GDM+/CVD+); women without GDM who developed CVD (GDM-/CVD+); those with GDM but no CVD (GDM+/CVD-); and those with neither GDM nor CVD (GDM-/CVD-). Lipids (total cholesterol, LDL, HDL, triglycerides) and glycemic variables (A1c, fasting glucose) were measured between 4.3+ or -3.0 and 4.8+ or -3.4 times over follow-up. Results On successive measurements at a median of 4.8, 7.1, and 8.7 years postpartum, respectively, each lipid and glycemic measure progressively worsened from GDM-/CVD- to GDM+/CVD- to GDM-/CVD+ to GDM+/CVD+ (all p<0.0001). At each point in time, each of the lipid and glycemic measures was significantly worse in GDM+/CVD+ compared to GDM+/CVD- (all p<0.001). Moreover, among women who did not develop CVD, all lipid and glycemic measures were significantly worse in those with previous GDM (all p<0.001 for GDM+/CVD- vs GDM-/CVD-). Mediation analyses revealed that the dominant determinants of CVD risk in women with GDM were A1c (56.0% mediation, 95%CI 47.4-67.8) and fasting glucose (47.4%, 38.8-60.8), followed by HDL (25.2%, 21.3-30.7) and triglycerides (12.1%, 9.7-15.6). Upon exclusion of those who developed diabetes during follow-up, the key determinants were HDL (40.8%), fasting glucose (37.7%), A1c (28.6%), triglycerides (21.0%), and LDL (9.9%). Conclusions Adverse glycemic and lipid measures mediate the elevated risk of CVD in women with previous GDM, with the impact of lipids particularly evident in those who do not develop diabetes. These findings thus identify potential targets for risk factor monitoring and ultimately early intervention towards the goal of primary prevention of CVD in this at-risk patient population. Keywords: Gestational diabetes, Cardiovascular disease, Risk factors, Glycemia, Lipids, Mediation analysis
OBJECTIVE:--To determine whether women with gestational diabetes mellitus (GDM) have an increased risk of cardiovascular disease (CVD) following pregnancy. RESEARCH DESIGN AND METHODS--All women aged ...20-49 years with live births between April 1994 and March 1997 in Ontario, Canada, were identified. Women with GDM were matched with 10 women without GDM and were followed for CVD. RESULTS:--The matched cohorts included 8,191 women with GDM and 81,262 women without GDM. Mean age at entry was 31 years, and median follow-up was 11.5 years. The hazard ratio for CVD events was 1.71 (95% CI 1.08-2.69). After adjustment for subsequent type 2 diabetes, the hazard ratio was attenuated (1.13 95% CI 0.67-1.89). CONCLUSIONS:--Young women with GDM had a substantially increased risk for CVD compared with women without GDM. Much of this increased risk was attributable to subsequent development of type 2 diabetes.
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