Cardiac Natriuretic Peptides, Obesity, and Insulin Resistance: Evidence from Two Community-Based Studies

Khan, Abigail; Cheng, Susan; Magnusson, Martin; Larson, Martin G.; Newton‐Cheh, Christopher; McCabe, Elizabeth L.; Coviello, Andrea D.; Florez, José C.; Fox, Caroline S.; Levy, Daniel; Robins, Sander J.; Arora, Pankaj; Bhasin, Shalender; Lam, Carolyn S.P.; Vasan, Ramachandran S.; Melander, Olle; Wang, Thomas J.

doi:10.1210/jc.2011-1182

Cited by 148 publications

(132 citation statements)

References 61 publications

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“…We and others have published evidence that elevations in NPs are associated with decreased incidence of diabetes mellitus,15, 29 and Mendelian randomization studies have suggested that these associations may be causal in nature 16. Thus, the increases in NT‐proBNP we observed with insulin therapy may represent a return of NP concentrations toward normal concentrations observed in nonobese patients 26. However, this explanation would not account for the differences in effects of insulin glargine and metformin, or for the fact that the observed changes were independent of improvements in glucose control.…”

Section: Discussionmentioning

confidence: 63%

“…This change was independent of changes in glucose control, body weight, and systolic blood pressure. Patients with T2DM tend to be obese (the median body mass index in LANCET was 35 kg/m 2 ), and obese patients have NT‐proBNP concentrations that are 10% to 30% lower than the nonobese, perhaps because of the hyperinsulinemia and insulin resistance commonly observed in obese patients 26, 27. Some have postulated that this natriuretic “handicap” might partially explain the susceptibility of obese and overweight individuals to salt retention, hypertension, and heart failure 27, 28.…”

Section: Discussionmentioning

confidence: 99%

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Randomized Trial of the Effects of Insulin and Metformin on Myocardial Injury and Stress in Diabetes Mellitus: A Post Hoc Exploratory Analysis

Srivastava

Pradhan

Cook

et al. 2017

JAHA

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BackgroundSubclinical myocardial injury, as measured by high‐sensitivity cardiac troponin T (hsTnT), and myocardial stress, as measured by N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), are related to glycemic control in patients with type 2 diabetes mellitus, and are strong predictors of adverse cardiovascular outcomes. We sought to determine whether antihyperglycemic therapy improves measures of myocardial injury and myocardial stress in patients with type 2 diabetes mellitus.Methods and ResultsWe randomized, in a 2×2 factorial fashion, 438 patients with type 2 diabetes mellitus to insulin glargine, metformin, the combination, or placebo and measured changes in NT‐proBNP and hsTnT after 12 weeks of therapy. At baseline, the median (Q1–Q3) plasma concentration was 35.4 (15.7–86.3) ng/L for NT‐proBNP and 6.7 (4.6–10.1) ng/L for hsTnT. The adjusted (95% confidence interval) change in NT‐proBNP concentration was 20.7% (7.9–35.0) in the insulin arm compared with 0.13% (−10.8 to 12.5) in the no‐insulin arm (P=0.03 for comparison). These changes were not related to changes in fasting or postprandial glucose, glycated hemoglobin, weight, blood pressure, or inflammation. In the metformin arm, the adjusted change in NT‐proBNP was 7.8% (−3.7 to 20.7) compared with 13.0% (0.72–26.8) in the no‐metformin arm (P=0.58). No significant changes in hsTnT concentrations were observed for any of the treatment arms.ConclusionsInsulin glargine was associated with a significant 20.7% increase in NT‐proBNP, a marker of myocardial stress, after 12 weeks of therapy. No change in hsTnT, a marker of myocardial injury, was observed. The changes were independent of substantial improvements in glucose control.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00366301.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Randomized Trial of the Effects of Insulin and Metformin on Myocardial Injury and Stress in Diabetes Mellitus: A Post Hoc Exploratory Analysis

Srivastava

Pradhan

Cook

et al. 2017

JAHA

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“…independently of BMI [30,31]. The mechanisms underlying the close association of BNP production with plasma FFAs and insulin resistance and remain to be elucidated.…”

Section: Resultsmentioning

confidence: 99%

Cardiac production of B-type natriuretic peptide is inversely related to the plasma level of free fatty acids in obese individuals - possible involvement of the insulin resistance -

Mizuno¹,

Harada²,

Katoh

et al. 2013

Endocr J

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“…In turn, this fluid retention would be the trigger for a pressure-diuresis phenomenon and a maintained urinary output, probably potentiated by higher albumin levels. This increase in insulin could also reflect an insulin-resistant state in high BMI patients, which is inherent to obese individuals [44,45] . In addition, in our study high BMI was associated with lower Pro-BNP levels, which is in agreement with other publications that report the association between hyperinsulinemia and low Pro-BNP patients in obesity [15,[45][46][47] .…”

mentioning

confidence: 99%

Residual urinary output in high body mass index individuals on chronic hemodialysis: A disregarded life vest?

Trimarchi¹

2014

WJN

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AIM:To assess residual diuresis and diverse variables according to body mass index (BMI). METHODS:Cross-sectional study (n = 57), with 3 groups. Group A: BMI < 25, n = 22; Group B: BMI 25-30, n = 15; Group C: BMI > 30, n = 20. Diuresis, hematocrit, albumin, C-reactive protein, Malnutrition inflammatory score, Pro-BNP, Troponin T, leptin and insulin levels are expressed as median and ranges (r). RESULTS:Albumin (g/dL): GA vs GC, vs 3.85 (r3.40-4.90), P = 0.02. Diuresis (mL/d): GA 690 (r0-1780); GB 660 (r60-1800); GC 840 (r40-2840).Diuresis GA vs GC, P = 0.01. Leptin (ng/mL): GA vs GC, vs GC,.50), P < 0.001. Insulin (µU/mL): GA vs GB, vs 11.50 (r4-38), P = 0.02; GA vs GC, Core tip: Cardiovascular disease is the major cause of death in hemodialysis, while residual diuresis and increased body mass index (BMI) are associated with better survival. We found that an elevated BMI > 30 associated positively with higher diuresis, insulin levels and albuminemia. This higher urinary output dialysis individuals with BMI > 30%, may reflect water retention, in part due to hyperinsulinemia, hyperleptinemia and secondary higher ultrafiltration rates. The ability to excrete water correlates negatively and significantly with Troponin T and Pro-BNP levels, reflecting lower myocardial and vascular overload. High BMI-associated better survival may be explained by better diuresis, and lower cardiovascular stress.

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Cardiac Natriuretic Peptides, Obesity, and Insulin Resistance: Evidence from Two Community-Based Studies

Cited by 148 publications

References 61 publications

Randomized Trial of the Effects of Insulin and Metformin on Myocardial Injury and Stress in Diabetes Mellitus: A Post Hoc Exploratory Analysis

Randomized Trial of the Effects of Insulin and Metformin on Myocardial Injury and Stress in Diabetes Mellitus: A Post Hoc Exploratory Analysis

Cardiac production of B-type natriuretic peptide is inversely related to the plasma level of free fatty acids in obese individuals - possible involvement of the insulin resistance -

Residual urinary output in high body mass index individuals on chronic hemodialysis: A disregarded life vest?

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