Association of dietary sodium intake with atherogenesis in experimental diabetes and with cardiovascular disease in patients with Type 1 diabetes

2013 ◽  
Vol 124 (10) ◽  
pp. 617-626 ◽  
Author(s):  
Chris Tikellis ◽  
Raelene J. Pickering ◽  
Despina Tsorotes ◽  
Valma Harjutsalo ◽  
Lena Thorn ◽  
...  

It is recommended that individuals with diabetes restrict their dietary sodium intake. However, although salt intake is correlated with BP (blood pressure), it also partly determines the activation state of the RAAS (renin–angiotensin–aldosterone system), a key mediator of diabetes-associated atherosclerosis. apoE KO (apolipoprotein E knockout) mice were allocated for the induction of diabetes with streptozotocin or citrate buffer (controls) and further randomized to isocaloric diets containing 0.05%, 0.3% or 3.1% sodium with or without the ACEi [ACE (angiotensin-converting enzyme) inhibitor] perindopril. After 6 weeks of study, plaque accumulation was quantified and markers of atherogenesis were assessed using RT–PCR (reverse transcription–PCR) and ELISA. The association of sodium intake and adverse cardiovascular and mortality outcomes were explored in 2648 adults with Type 1 diabetes without prior CVD (cardiovascular disease) from the FinnDiane study. A 0.05% sodium diet was associated with increased plaque accumulation in diabetic apoE KO mice, associated with activation of the RAAS. By contrast, a diet containing 3.1% sodium suppressed atherogenesis associated with suppression of the RAAS, with an efficacy comparable with ACE inhibition. In adults with Type 1 diabetes, low sodium intake was also associated with an increased risk of all-cause mortality and new-onset cardiovascular events. However, high sodium intake was also associated with adverse outcomes, leading to a J-shaped relationship overall. Although BP lowering is an important goal for the management of diabetes, off-target actions to activate the RAAS may contribute to an observed lack of protection from cardiovascular complications in patients with Type 1 diabetes with low sodium intake.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Eva O. Melin ◽  
Jonatan Dereke ◽  
Magnus Hillman

Abstract Background Low levels of the soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) and depression are linked to cardiovascular disease. Galectin-3, inadequate glycemic control and low high-density lipoprotein (HDL)-cholesterol levels were previously linked to depression in these patients with type 1 diabetes mellitus (T1DM). The main aim was to explore whether sTWEAK was associated with depression. A secondary aim was to explore diabetes related variables associated with low sTWEAK. Methods Cross-sectional design. T1DM patients (n = 283, men 56%, age18–59 years) were consecutively recruited from one specialist diabetes clinic. Depression was defined as Hospital Anxiety and Depression Scale-Depression sub scale ≥8 points. Blood samples, anthropometrics and blood pressure were collected, supplemented with data from electronic health records. Enzyme linked immunosorbent assays were used to measure sTWEAK and galectin-3. Low sTWEAK was defined as < 7.2 ng/ml and high galectin-3 as ≥2.6 ng/ml. Multiple logistic regression analyses were performed, calibrated and validated for goodness of fit. We adjusted for age, sex, diabetes duration, galectin-3, metabolic variables, serum-creatinine, smoking, physical inactivity, medication, and cardiovascular complications. Results For 29 depressed versus 254 non-depressed patients the prevalence rates were for low sTWEAK: 93 and 68% (p = 0.003) and for high galectin-3: 34 and 13% (p = 0.005) respectively. HDL-cholesterol levels were lower for the depressed (p = 0.015). Patients with low sTWEAK versus high sTWEAK had lower usage of continuous subcutaneous insulin infusion (CSII) (6% versus 17%, p = 0.005). Low sTWEAK (adjusted odds ratio (AOR) 9.0, p = 0.006), high galectin-3 (AOR 6.3, p = 0.001), HDL-cholesterol (per mmol/l) (AOR 0.1, p = 0.006), use of antidepressants (AOR 8.4, p < 0.001), and age (per year) (AOR 1.05, p = 0.027) were associated with depression. CSII (AOR 0.3, p = 0.003) and depression (AOR 7.1, p = 0.009) were associated with low sTWEAK. Conclusions Lower levels of sTWEAK and HDL-cholesterol and higher levels of galectin-3 were independently associated with depression in T1DM. These factors might all contribute to the increased risk for cardiovascular disease and mortality previously demonstrated in patients with depression. CSII (inversely) and depression were independently associated with low sTWEAK levels.


Author(s):  
Jiang He ◽  
Jian-Feng Huang ◽  
Changwei Li ◽  
Jing Chen ◽  
Xiangfeng Lu ◽  
...  

Cross-sectional studies have reported that high sodium sensitivity is more common among individuals with hypertension. Experimental studies have also reported various animal models with sodium-resistant hypertension. It is unknown, however, whether sodium sensitivity and resistance precede the development of hypertension. We conducted a feeding study, including a 7-day low-sodium diet (1180 mg/day) followed by a 7-day high-sodium diet (7081 mg/day), among 1718 Chinese adults with blood pressure (BP) <140/90 mm Hg. We longitudinally followed them over an average of 7.4 years. Three BP measurements and 24-hour urinary sodium excretion were obtained on each of 3 days during baseline observation, low-sodium and high-sodium interventions, and 2 follow-up studies. Three trajectories of BP responses to dietary sodium intake were identified using latent trajectory analysis. Mean (SD) changes in systolic BP were −13.7 (5.5), −4.9 (3.0), and 2.4 (3.0) mm Hg during the low-sodium intervention and 11.2 (5.3), 4.4 (4.1), and −0.2 (4.1) mm Hg during the high-sodium intervention ( P <0.001 for group differences) in high sodium-sensitive, moderate sodium-sensitive, and sodium-resistant groups, respectively. Compared with individuals with moderate sodium sensitivity, multiple-adjusted odds ratios (95% CIs) for incident hypertension were 1.43 (1.03–1.98) for those with high sodium sensitivity and 1.43 (1.03–1.99) for those with sodium resistance ( P =0.006 for nonlinear trend). Furthermore, a J-shaped association between systolic BP responses to sodium intake and incident hypertension was identified ( P <0.001). Similar results were observed for diastolic BP. Our study indicates that individuals with either high sodium sensitivity or sodium resistance are at an increased risk for developing hypertension.


2019 ◽  
Vol 10 ◽  
Author(s):  
Laura Gomes Nunes Melo ◽  
Paulo Henrique Morales ◽  
Karla Rezende Guerra Drummond ◽  
Deborah Conte Santos ◽  
Marcela Haas Pizarro ◽  
...  

2020 ◽  
Vol 41 (35) ◽  
pp. 3363-3373 ◽  
Author(s):  
Martin O’Donnell ◽  
Andrew Mente ◽  
Michael H Alderman ◽  
Adrian J B Brady ◽  
Rafael Diaz ◽  
...  

Abstract Several blood pressure guidelines recommend low sodium intake (&lt;2.3 g/day, 100 mmol, 5.8 g/day of salt) for the entire population, on the premise that reductions in sodium intake, irrespective of the levels, will lower blood pressure, and, in turn, reduce cardiovascular disease occurrence. These guidelines have been developed without effective interventions to achieve sustained low sodium intake in free-living individuals, without a feasible method to estimate sodium intake reliably in individuals, and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with moderate intake). In this review, we examine whether the recommendation for low sodium intake, reached by current guideline panels, is supported by robust evidence. Our review provides a counterpoint to the current recommendation for low sodium intake and suggests that a specific low sodium intake target (e.g. &lt;2.3 g/day) for individuals may be unfeasible, of uncertain effect on other dietary factors and of unproven effectiveness in reducing cardiovascular disease. We contend that current evidence, despite methodological limitations, suggests that most of the world’s population consume a moderate range of dietary sodium (2.3–4.6g/day; 1–2 teaspoons of salt) that is not associated with increased cardiovascular risk, and that the risk of cardiovascular disease increases when sodium intakes exceed 5 g/day. While current evidence has limitations, and there are differences of opinion in interpretation of existing evidence, it is reasonable, based upon observational studies, to suggest a population-level mean target of &lt;5 g/day in populations with mean sodium intake of &gt;5 g/day, while awaiting the results of large randomized controlled trials of sodium reduction on incidence of cardiovascular events and mortality.


2021 ◽  
Author(s):  
Rose Gubitosi-Klug ◽  
Xiaoyu Gao ◽  
Rodica Pop-Busui ◽  
Ian H de Boer ◽  
Neill White ◽  
...  

<b>Objective:</b> We examined whether the presence of microvascular complications was associated with increased subsequent risk of cardiovascular disease (CVD) among participants with type 1 diabetes in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study followed for over 35 years. <p><b>Research Design and Methods:</b> Standardized longitudinal data collection included: 1) stereoscopic seven-field retinal fundus photography centrally-graded for retinopathy stage and clinically significant macular edema; 2) urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR); 3) cardiovascular autonomic neuropathy (CAN) reflex testing; and 4) adjudicated CVD events, including death from cardiovascular disease, nonfatal myocardial infarction, stroke, subclinical myocardial infarction on ECG, confirmed angina, or coronary artery revascularization. Cox proportional hazard models assessed the association of microvascular complications with subsequent risk of CVD. </p> <p><b>Results:</b> 239 participants developed CVD, including 120 participants who suffered major adverse cardiovascular events (MACE) defined as non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. The presence of microvascular disease (diabetic retinopathy, kidney disease, or CAN) was associated with increased risk of subsequent CVD and MACE (hazard ratios 1.86 to 3.18 and 2.09 to 3.63, respectively); associations that remained significant after adjusting for age and HbA1c. After adjustment for traditional CVD risk factors, however, only sustained AER≥30 mg/24hr occurring alone and/or with eGFR<60 ml/min/1.73m, and the presence of both retinal and kidney disease remained associated with CVD. </p> <p><b>Conclusions:</b> Advanced microvascular disease, especially moderate to severe albuminuria or eGFR<60 ml/min/1.73m<sup>2</sup>, conveyed an increased risk of subsequent cardiovascular disease in the DCCT/EDIC cohort. </p>


Diabetes Care ◽  
2011 ◽  
Vol 34 (4) ◽  
pp. 861-866 ◽  
Author(s):  
M. C. Thomas ◽  
J. Moran ◽  
C. Forsblom ◽  
V. Harjutsalo ◽  
L. Thorn ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3232
Author(s):  
Andrew Mente ◽  
Martin O’Donnell ◽  
Salim Yusuf

Several health organizations recommend low sodium intake (below 2.3 g/day, 5.8 g/day of salt) for entire populations, on the premise that lowering of sodium intake, irrespective of its level of intake, will lower blood pressure and, in turn, will result in a lower incidence of cardiovascular disease. These guidelines were developed without effective interventions to achieve long term sodium intakes at low levels in free-living individuals and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with average levels of intake). In this review, we examine whether advice to consume low amounts of sodium is supported by robust evidence. We contend that current evidence indicates that most people around the world consume a moderate range of dietary sodium (3 to 5 g/day), that this level of intake is associated with the lowest risk of cardiovascular disease and mortality, and that the risk of adverse health outcomes increases when sodium intakes exceeds 5 g/day or is below 3 g/day. While the current evidence has limitations, it is reasonable, based upon prospective cohort studies, to suggest a mean target of below 5 g/day in populations, while awaiting the results of large randomized controlled trials of sodium reduction on cardiovascular disease and death.


Diabetologia ◽  
2009 ◽  
Vol 52 (12) ◽  
pp. 2590-2593 ◽  
Author(s):  
A. Möllsten ◽  
A. Jorsal ◽  
M. Lajer ◽  
N. Vionnet ◽  
L. Tarnow

2021 ◽  
Author(s):  
Rose Gubitosi-Klug ◽  
Xiaoyu Gao ◽  
Rodica Pop-Busui ◽  
Ian H de Boer ◽  
Neill White ◽  
...  

<b>Objective:</b> We examined whether the presence of microvascular complications was associated with increased subsequent risk of cardiovascular disease (CVD) among participants with type 1 diabetes in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study followed for over 35 years. <p><b>Research Design and Methods:</b> Standardized longitudinal data collection included: 1) stereoscopic seven-field retinal fundus photography centrally-graded for retinopathy stage and clinically significant macular edema; 2) urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR); 3) cardiovascular autonomic neuropathy (CAN) reflex testing; and 4) adjudicated CVD events, including death from cardiovascular disease, nonfatal myocardial infarction, stroke, subclinical myocardial infarction on ECG, confirmed angina, or coronary artery revascularization. Cox proportional hazard models assessed the association of microvascular complications with subsequent risk of CVD. </p> <p><b>Results:</b> 239 participants developed CVD, including 120 participants who suffered major adverse cardiovascular events (MACE) defined as non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. The presence of microvascular disease (diabetic retinopathy, kidney disease, or CAN) was associated with increased risk of subsequent CVD and MACE (hazard ratios 1.86 to 3.18 and 2.09 to 3.63, respectively); associations that remained significant after adjusting for age and HbA1c. After adjustment for traditional CVD risk factors, however, only sustained AER≥30 mg/24hr occurring alone and/or with eGFR<60 ml/min/1.73m, and the presence of both retinal and kidney disease remained associated with CVD. </p> <p><b>Conclusions:</b> Advanced microvascular disease, especially moderate to severe albuminuria or eGFR<60 ml/min/1.73m<sup>2</sup>, conveyed an increased risk of subsequent cardiovascular disease in the DCCT/EDIC cohort. </p>


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