Overweight and obesity are important risk factors of gestational diabetes mellitus (GDM). Clustering of metabolic risk factors in early pregnancy may be a potential pathogenesis between the link of ...overweight/obesity and GDM. Since it remains unexplored, we investigated if overweight and obesity are associated with clustering of metabolic risk factors in early pregnancy and the risk of GDM in this cohort study.
Total 527 women who visited National Taiwan University Hospital for prenatal care in between November 2013 to April 2018 were enrolled. Risk factors of GDM in the first prenatal visit (FPV) were recorded. Overweight/obesity was defined if body mass index ≥24 kg/m2. GDM was diagnosed from the result of a 75g oral glucose tolerance test in 24-28 gestational weeks.
Overweight/obesity was associated with clustering of metabolic risk factors of GDM, including high fasting plasma glucose, high HbA1c, insulin resistance, high plasma triglyceride and elevated blood pressure in FPV (p<0.05). There was a positive relationship between the number of metabolic risk factors and the incidence of GDM (p <0.05). The odds ratios of HbA1c and diastolic blood pressure were higher in overweight/obese women, compared with those in normal-weight women.
Overweight/obesity is associated with clustering of metabolic risk factors in early pregnancy, which is correlated with higher risk of GDM. Our findings suggest that metabolic risk factors during early pregnancy should be evaluated in overweight/obese women.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: The Roux-en-Y gastric bypass is effective in achieving established diabetes treatment targets, but durability is unknown. OBJECTIVE: To compare durability of Roux-en-Y gastric bypass ...added to intensive lifestyle and medical management in achieving diabetes control targets. DESIGN, SETTING, AND PARTICIPANTS: Observational follow-up of a randomized clinical trial at 4 sites in the United States and Taiwan, involving 120 participants who had a hemoglobin A1c (HbA1c) level of 8.0% or higher and a body mass index between 30.0 and 39.9 (enrolled between April 2008 and December 2011) were followed up for 5 years, ending in November 2016. INTERVENTIONS: Lifestyle-intensive medical management intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2 years, with and without (60 participants each) Roux-en-Y gastric bypass surgery followed by observation to year 5. MAIN OUTCOMES AND MEASURES: The American Diabetes Association composite triple end point of hemoglobin A1c less than 7.0%, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg at 5 years. RESULTS: Of 120 participants who were initially randomized (mean age, 49 years SD, 8 years, 72 women 60%), 98 (82%) completed 5 years of follow-up. Baseline characteristics were similar between groups: mean (SD) body mass index 34.4 (3.2) for the lifestyle–medical management group and 34.9 (3.0) for the gastric bypass group and had hemoglobin A1c levels of 9.6% (1.2) and 9.6% (1.0), respectively. At 5 years, 13 participants (23%) in the gastric bypass group and 2 (4%) in the lifestyle-intensive medical management group had achieved the composite triple end point (difference, 19%; 95% CI, 4%-34%; P = .01). In the fifth year, 31 patients (55%) in the gastric bypass group vs 8 (14%) in the lifestyle–medical management group achieved an HbA1c level of less than 7.0% (difference, 41%; 95% CI, 19%-63%; P = .002). Gastric bypass had more serious adverse events than did the lifestyle–medical management intervention, 66 events vs 38 events, most frequently gastrointestinal events and surgical complications such as strictures, small bowel obstructions, and leaks. Gastric bypass had more parathyroid hormone elevation but no difference in B12 deficiency. CONCLUSIONS AND RELEVANCE: In extended follow-up of obese adults with type 2 diabetes randomized to adding gastric bypass compared with lifestyle and intensive medical management alone, there remained a significantly better composite triple end point in the surgical group at 5 years. However, because the effect size diminished over 5 years, further follow-up is needed to understand the durability of the improvement. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00641251
Several recent advances provide multiple health benefits to individuals with type 2 diabetes mellitus (T2DM). Pharmacological therapy is governed by person‐centered factors, including comorbidities ...and treatment goals. Adults with T2DM who have an established/high risk of atherosclerotic cardiovascular disease, heart failure, and/or chronic kidney disease, require a treatment regimen that includes agents that are proven to reduce cardiorenal risk. Weight management plays a key role in reducing glucose for patients with T2DM. A glucose‐reduction treatment regimen must consider weight management. Sodium glucose co‐transporter 2 (SGLT2) inhibitors reduce the risk of heart failure, cardiovascular and renal events. Glucagon‐like peptide‐1 (GLP‐1) receptor agonists allow better control of glycemia, promote weight loss and reduce the risk of cardiovascular events. Newer Glucose‐dependent insulinotropic polypeptide (GIP) and GLP‐1 dual agonist, which activate GIP and GLP‐1 receptors improve glycemic control and promote greater weight loss than GLP‐1 receptor agonists. Several novel drugs are in the clinical development phase. This review pertains to recent advances in pharmacological management of type 2 diabetes.
Whether retroperitoneal fat should be included in the measurement of visceral fat remains controversial. We compared the relationships of fat areas in peritoneal, retroperitoneal, and subcutaneous ...compartments to metabolic syndrome, adipokines, and incident hypertension and diabetes.
We enrolled 432 adult participants (153 men and 279 women) in a community-based cohort study. Computed tomography at the umbilicus level was used to measure the fat areas.
Retroperitoneal fat correlated significantly with metabolic syndrome (adjusted odds ratio (OR), 5.651, p<0.05) and the number of metabolic abnormalities (p<0.05). Retroperitoneal fat area was significantly associated with blood pressure, plasma glycemic indices, lipid profile, C-reactive protein, adiponectin (r = -0.244, P<0.05), and leptin (r = 0.323, p<0.05), but not plasma renin or aldosterone concentrations. During the 2.94 ± 0.84 years of follow-up, 32 participants developed incident hypertension. Retroperitoneal fat area (hazard ration (HR) 1.62, p = 0.003) and peritoneal fat area (HR 1.62, p = 0.009), but not subcutaneous fat area (p = 0.14) were associated with incident hypertension. Neither retroperitoneal fat area, peritoneal fat area, nor subcutaneous fat areas was associated with incident diabetes after adjustment.
Retroperitoneal fat is similar to peritoneal fat, but differs from subcutaneous fat, in terms of its relationship with metabolic syndrome and incident hypertension. Retroperitoneal fat area should be included in the measurement of visceral fat for cardio-metabolic studies in human.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prior cross-sectional analyses have demonstrated an association between subclinical hypothyroidism and metabolic syndrome and selected components. However, the temporal relation between metabolic ...syndrome and declining thyroid function remains unclear. In a prospective study, an unselected cohort of 66,822 participants with and without metabolic syndrome were followed. A proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% CIs for hypothyroidism. Exploratory analyses for the relation between components of metabolic syndrome and declining thyroid function were also undertaken. During an average follow-up of 4.2 years, the incident rates for subclinical hypothyroidism were substantially higher in participants who began the study with metabolic syndrome compared with metabolically normal controls. After controlling for risk factors, patients with metabolic syndrome were at a 21% excess risk of developing subclinical hypothyroidism (adjusted HR 1.21; 95% CI 1.03-1.42). When individual components were analyzed, an increased risk of subclinical hypothyroidism was associated with high blood pressure (1.24; 1.04-1.48) and high serum triglycerides (1.18; 1.00-1.39), with a trend of increasing risk as participants had additional more components. Individuals with metabolic syndrome are at a greater risk for developing subclinical hypothyroidism, while its mechanisms and temporal consequences of this observation remain to be determined.
Functional decline of stem cell transplantation in ageing hosts is well documented. The mechanism for this is poorly understood, although it is known that advancing age does not provide an optimal ...milieu for exogenous stem cells to survive, engraft and differentiate. We showed that n‐butylidenephthalide improved human adipose–derived stem cell (hADSC) engraftment via attenuating the production of reactive oxygen species (ROS). It remained unclear whether pre‐treated hosts with n‐butylidenephthalide can rejuvenate the ageing heart and improve hADSC engraftment by regulating the ROS/NLRP3 inflammasome‐mediated cardiac fibrosis after myocardial infarction. One hour after coronary ligation, hADSCs were transplanted into the hearts of young and ageing Wistar rats that were pre‐treated with or without n‐butylidenephthalide for 3 days. At day 3 after infarction, myocardial infarction was associated with an increase in ROS levels and NLRP3 inflammasome activity with age. hADSC transplant effectively provided a significant decrease in ROS levels, NLRP3 inflammasome activity, IL‐1β levels and cardiac fibrosis in either young or old infarcted rats. However, the beneficial effects of hADSCs were greater in young compared with old rats in terms of NLRP3 inflammasome activity. The infarcted ageing rats pre‐conditioned by n‐butylidenephthalide improved engraftment and differentiation of hADSCs and additionally attenuated cardiac fibrosis compared with hADSCs alone. The anti‐inflammation effects of n‐butylidenephthalide were reversed by SIN‐1. In conclusions, the increased NLRP3 inflammasome activity plays the pathogenesis of ageing‐related functional hADSC decline in the ageing hosts. n‐butylidenephthalide‐pre‐treated ageing hosts reversibly ameliorate the harsh microenvironments, improve stem cell engraftment and attenuate cardiac fibrosis after myocardial infarction.
Cognitive impairment is a serious side effect of post-myocardial infarction (MI) course. We have recently demonstrated that human adipose-derived stem cells (hADSCs) ameliorated myocardial injury ...after MI by attenuating reactive oxygen species (ROS) levels. Here, we studied whether the beneficial effects of intramyocardial hADSC transplantation can extend to the brain and how they may attenuate cognitive dysfunction via modulating ROS after MI. After coronary ligation, male Wistar rats were randomized via an intramyocardial route to receive either vehicle, hADSC transplantation (1 × 10
6
cells), or the combination of hADSCs and 3-Morpholinosydnonimine (SIN-1, a peroxynitrite donor). Whether hADSCs migrated into the hippocampus was assessed by using human-specific primers in qPCR reactions. Passive avoidance test was used to assess cognitive performance. Postinfarction was associated with increased oxidative stress in the myocardium, circulation, and hippocampus. This was coupled with decreased numbers of dendritic spines as well as a significant downregulation of synaptic plasticity consisting of synaptophysin and PSD95. Step-through latency during passive avoidance test was impaired in vehicle-treated rats after MI. Intramyocardial hADSC injection exerted therapeutic benefits in improving cardiac function and cognitive impairment. None of hADSCs was detected in rat’s hippocampus at the 3rd day after intramyocardial injection. The beneficial effects of hADSCs on MI-induced histological and cognitive changes were abolished after adding SIN-1. MI-induced ROS attacked the hippocampus to induce neurodegeneration, resulting in cognitive deficit. The remotely intramyocardial administration of hADSCs has the capacity of improved synaptic neuroplasticity in the hippocampus mediated by ROS, not the cell engraftment, after MI.
Key messages
Human adipose-derived stem cells (hADSCs) ameliorated injury after myocardial infarction by attenuating reactive oxygen species (ROS) levels.
Intramyocardial administration of hADSCs remotely exerted therapeutic benefits in improving cognitive impairment after myocardial infarction.
The improved synaptic neuroplasticity in the hippocampus was mediated by hADSC-inhibiting ROS, not by the stem cell engraftment.
Abstract
Obesity and type 2 diabetes have reached pandemic proportion. ALDH2 (acetaldehyde dehydrogenase 2, mitochondrial) is the key metabolizing enzyme of acetaldehyde and other toxic aldehydes, ...such as 4-hydroxynonenal. A missense Glu504Lys mutation of the
ALDH2
gene is prevalent in 560 million East Asians, resulting in reduced ALDH2 enzymatic activity. We find that male
Aldh2
knock-in mice mimicking human Glu504Lys mutation were prone to develop diet-induced obesity, glucose intolerance, insulin resistance, and fatty liver due to reduced adaptive thermogenesis and energy expenditure. We find reduced activity of ALDH2 of the brown adipose tissue from the male
Aldh2
homozygous knock-in mice. Proteomic analyses of the brown adipose tissue from the male
Aldh2
knock-in mice identifies increased 4-hydroxynonenal-adducted proteins involved in mitochondrial fatty acid oxidation and electron transport chain, leading to markedly decreased fatty acid oxidation rate and mitochondrial respiration of brown adipose tissue, which is essential for adaptive thermogenesis and energy expenditure.
AD-9308
is a water-soluble, potent, and highly selective ALDH2 activator.
AD-9308
treatment ameliorates diet-induced obesity and fatty liver, and improves glucose homeostasis in both male
Aldh2
wild-type and knock-in mice. Our data highlight the therapeutic potential of reducing toxic aldehyde levels by activating ALDH2 for metabolic diseases.
Stem cells can modify macrophage phenotypes; however, the mechanisms remain unclear. We investigated whether n-butylidenephthalide (BP) primed adipose-derived stem cells (ADSCs) attenuated cardiac ...fibrosis via regulating macrophage phenotype by a PI3K/STAT3-dependent pathway in postinfarcted rats. Male Wistar rats after coronary ligation were allocated to receive either intramyocardial injection of vehicle, ADSCs (1 × 106 cells), BP-preconditioned ADSCs, (BP + lithium)-preconditioned ADSCs, (BP + LY294002)-preconditioned ADSCs, and (BP + S3I-201)-preconditioned ADSCs. ADSCs were primed for 16 h before implantation. BP-pretreated ADSCs increased the cell viability compared with naive ADSCs in the in vitro experiments. Infarct sizes were similar among the infarcted groups at the acute and chronic stages of infarction. At day 3 after infarction, post-infarction was associated with increased M1 macrophage infiltration, which was inhibited by administering naive ADSCs. Compared with naive ADSCs, BP-preconditioned ADSCs provided a significant increase of Akt and STAT3 phosphorylation, STAT3 activity, STAT3 nuclear translocation, myocardial IL-10 levels, and the percentage of M2 macrophage infiltration. The effects of BP on M2 polarization were reversed by LY294002 or S3I-201. Furthermore, the phosphorylation of both Akt and STAT3 was abolished by LY294002, whereas Akt phosphorylation was not affected following the inhibition of STAT3. The addition of lithium did not have additional effects compared with BP alone. After 4 weeks of implantation, ADSCs remained in the myocardium, and reduced fibrosis and improved cardiac function. BP-preconditioned ADSCs provided superior cardioprotection, greater ADSC engraftment, and antifibrotic effects compared with naive ADSCs. These results suggest that BP-pretreated ADSCs polarize macrophages into M2 cells more efficiently than naive ADSCs via the PI3K/STAT3 pathway.
To evaluate chronic kidney disease (CKD) and cardiovascular outcomes in TECOS (Clinical trial reg. no. NCT00790205, clinicaltrials.gov) participants with type 2 diabetes and cardiovascular disease ...treated with sitagliptin, a dipeptidyl peptidase 4 inhibitor, according to baseline estimated glomerular filtration rate (eGFR).
We used data from 14,671 TECOS participants assigned in a double-blind design to receive sitagliptin or placebo added to existing therapy, while aiming for glycemic equipoise between groups. Cardiovascular and CKD outcomes were evaluated over a median period of 3 years, with participants categorized at baseline into eGFR stages 1, 2, 3a, and 3b (≥90, 60-89, 45-59, or 30-44 mL/min/1.73 m
, respectively).
Participants with eGFR stage 3b were older, were more often female, and had a longer duration of diabetes. Four-point major adverse cardiovascular event rates increased with lower baseline eGFR (3.52, 3.55, 5.74, and 7.34 events/100 patient-years for stages 1-3b, respectively). Corresponding adjusted hazard ratios for stages 2, 3a, and 3b versus stage 1 were 0.93 (95% CI 0.82-1.06), 1.28 (1.10-1.49), and 1.39 (1.13-1.72), respectively. Sitagliptin therapy was not associated with cardiovascular outcomes for any eGFR stage (interaction P values were all >0.44). Kidney function declined at the same rate in both treatment groups, with a marginally lower but constant eGFR difference (-1.3 mL/min/1.73 m
) in those participants who were assigned to sitagliptin. Treatment differences in these eGFR values remained after adjustment for region, baseline eGFR, baseline HbA
, time of assessment, and within-study HbA
levels.
Impaired kidney function is associated with worse cardiovascular outcomes. Sitagliptin has no clinically significant impact on cardiovascular or CKD outcomes, irrespective of baseline eGFR.
PDF
