Insulin sensitivity and pancreatic β-cell function in patients with primary aldosteronism
Open accessAbstract
Primary aldosteronism (PA) is associated with an increased risk for dysglycemia. However, the effects of hyperaldosteronism on insulin sensitivity and β-cell function are unclear. Using a cross-sectional study design, we assessed insulin sensitivity and pancreatic β-cell function from an oral glucose tolerance test (OGTT) in patients from two cohorts: subjects with PA (n = 21) and essential hypertension control (EHC) subjects (n = 22). Age, sex, BMI, and mean arterial pressure adjusted measures of insulin sensitivity and β-cell function were compared between the groups. PA individuals were less insulin sensitive compared to EHC subjects (Quantitative insulin sensitivity check index [QUICKI]: 0.340 ± 0.006 vs. 0.374 ± 0.013, p < 0.001; Matsuda index: 4.14 ± 0.49 vs. 7.87 ± 1.42, p < 0.001; SI: 11.45 ± 4.85 vs. 21.23 ± 6.11 dL/kg/min per μU/mL, p = 0.02). The hepatic insulin resistance index (HIRI) was higher in PA subjects (PA: 5.61 ± 1.01 vs. EHC: 4.13 ± 0.61, p = 0.002). The insulinogenic index (IGI), an index of β-cell function was higher in the PA cohort (PA: 1.49 ± 0.27 vs. 1.11 ± 0.21 μU/mL/mg/dL, p = 0.03). However, the oral disposition index (DI) was similar between the groups (PA: 4.77 ± 0.73 vs. EHC: 5.46 ± 0.85, p = 0.42), which likely accounts for the similar glucose tolerance between the two cohorts, despite lower sensitivity. In summary, insulin sensitivity is significantly lower in PA with an appropriately compensated β-cell function. These results suggest that…
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13 of 64 cited sources checked · 5 supported · 1 flagged · accuracy not yet measured
- Premisecitation
There was no difference in HOMA-IR between patients with primary aldosteronism and essential hypertensives.
“Similarly, there was no difference in HOMA-IR between PA subjects and EHs [50,22].”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [50] F. Fallo, P. Della Mea, N. Sonino, C. Bertello, M. Ermani, R. Vettor, F. Veglio, P. Mulatero, Adiponectin and insulin sensitivity in primary aldosteronism. Am. J. Hypertens. 20(8), 855–861 (2007). https://doi.org/10.1016/j.amjhyper.2007.03.012 source
The Results report that the HOMA index was significantly higher in patients with primary aldosteronism than in those with low-renin essential hypertension. No difference was found only in the subsets with metabolic syndrome, a qualification absent from the citing sentence. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured - cites [22] L.M. Mosso, C.A. Carvajal, A. Maiz, E.H. Ortiz, C.R. Castillo, R.A. Artigas, C.E. Fardella, A possible association between primary aldosteronism and a lower beta-cell function. J. Hypertens. 25(10), 2125–2130 (2007). https://doi.org/10.1097/HJH.0b013e3282861fa4 source
- Premisecitation
Primary aldosteronism is associated with an increased risk of dysglycemia.
“Primary aldosteronism (PA) is associated with increased risk for dysglycemia.”
Quote in the paperSubstantial claim2 of 10 sources checked- cites [5] C. Catena, R. Lapenna, S. Baroselli, E. Nadalini, G. Colussi, M. Novello, G. Favret, A. Melis, A. Cavarape, L.A. Sechi, Insulin sensitivity in patients with primary aldosteronism: a follow-up study. J. Clin. Endocrinol. Metab. 91(9), 3457–3463 (2006). https://doi.org/10.1210/jc.2006-0736 source
- cites [2] G.L. Hundemer, Primary aldosteronism: cardiovascular outcomes pre- and post-treatment. Curr. Cardiol. Rep. 21(9), 93 (2019). https://doi.org/10.1007/s11886-019-1185-x source
- cites [6] F. Fallo, F. Veglio, C. Bertello, N. Sonino, P. Della Mea, M. Ermani, F. Rabbia, G. Federspil, P. Mulatero, Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J. Clin. Endocrinol. Metab. 91(2), 454–459 (2006). https://doi.org/10.1210/jc.2005-1733 source
- cites [7] J.M. Connell, S.M. MacKenzie, E.M. Freel, R. Fraser, E. Davies, A lifetime of aldosterone excess: long-term consequences of altered regulation of aldosterone production for cardiovascular function. Endocr. Rev. 29(2), 133–154 (2008). https://doi.org/10.1210/er.2007-0030 source
- cites [8] G. Giacchetti, V. Ronconi, F. Turchi, L. Agostinelli, F. Mantero, S. Rilli, M. Boscaro, Aldosterone as a key mediator of the cardiometabolic syndrome in primary aldosteronism: an observational study. J. Hypertens. 25(1), 177–186 (2007). https://doi.org/10.1097/HJH.0b013e3280108e6f source
- cites [9] J.M. Luther, Effects of aldosterone on insulin sensitivity and secretion. Steroids 91, 54–60 (2014). https://doi.org/10.1016/j.steroids.2014.08.016 source
- cites [10] V. Ronconi, F. Turchi, S. Rilli, D. Di Mattia, L. Agostinelli, M. Boscaro, G: Giacchetti, Metabolic syndrome in primary aldosteronism and essential hypertension: relationship to adiponectin gene variants. Nutr. Metab. Cardiovasc. Dis. 20(2), 93–100 (2010). https://doi.org/10.1016/j.numecd.2009.03.007 source
- cites [11] J.W. Funder, M. Reincke, Aldosterone: a cardiovascular risk factor? Biochim. Biophys. Acta 1802(12), 1188–1192 (2010). https://doi.org/10.1016/j.bbadis.2010.08.005 source
The Primary aldosteronism section (page not available in our copy) reports more than 50% higher diabetes prevalence in one matched comparison, supporting an association with dysglycemia. It also reports several studies that found no significant difference in diabetes or glucose measures and cautions that the findings differ across studies. The unqualified claim overstates that mixed evidence. (LLM, conf=0.85)
Experimental — accuracy not yet measured - cites [12] Z. Somloova, J. Widimsky Jr., J. Rosa, D. Wichterle, B. Strauch, O. Petrak, T. Zelinka, J. Vlkova, M. Masek, J. Dvorakova, R. Holaj, The prevalence of metabolic syndrome and its components in two main types of primary aldosteronism. J. Hum. Hypertens. 24(10), 625–630 (2010). https://doi.org/10.1038/jhh.2010.65 source
- cites [13] G. Colussi, C. Catena, R. Lapenna, E. Nadalini, A. Chiuch, L.A. Sechi, Insulin resistance and hyperinsulinemia are related to plasma aldosterone levels in hypertensive patients. Diabetes Care 30(9), 2349–2354 (2007). https://doi.org/10.2337/dc07-0525 source
- Premisecitation
Aldosterone reduces insulin secretion through direct effects on the β-cell.
“Aldosterone reduces insulin secretion by direct effects on the β-cell [36-38].”
Quote in the paperNot a substantial claim1 of 3 sources checked- cites [36] J.F. Ndisang, A. Jadhav, The heme oxygenase system attenuates pancreatic lesions and improves insulin sensitivity and glucose metabolism in deoxycorticosterone acetate hypertension. Am. J. Physiol. Regul. Integr. Comp. Physiol. 298(1), R211–R223 (2010). https://doi.org/10.1152/ajpregu.91000.2008 source
- cites [37] J. Pierluissi, F.O. Navas, S.J. Ashcroft, Effect of adrenal steroids on insulin release from cultured rat islets of Langerhans. Diabetologia 29(2), 119–121 (1986). https://doi.org/10.1007/BF00456122 source
The Results and Discussion report that aldosterone directly applied to cultured rat islets reduced glucose-stimulated insulin release. The experiments used whole islets, however, and do not establish that aldosterone acted directly on β-cells rather than elsewhere within the islets. (LLM, conf=0.83)
Experimental — accuracy not yet measured - cites [38] J.C. Henquin, A.E. Lambert, Cationic environment and dynamics of insulin secretion. II Effect of a high concentration of potassium. Diabetes 23(12), 933–942 (1974). https://doi.org/10.2337/diab.23.12.933 source
- Premisecitation
In vitro and rodent studies show that aldosterone-induced mineralocorticoid activation impairs insulin sensitivity in adipocytes and skeletal muscle.
“In vitro and rodent studies show that aldosterone-induced mineralocorticoid activation impairs insulin sensitivity in adipocytes and skeletal muscle [40,41].”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [40] J.R. Sowers, A. Whaley-Connell, M. Epstein, Narrative review: the emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension. Ann. Intern. Med. 150(11), 776–783 (2009). https://doi.org/10.7326/0003-4819-150-11-200906020-00005 source
In “Aldosterone Interactions With Adipose Tissue” (page unavailable), the review reports impaired insulin-induced glucose uptake in rodent fat tissue. “Aldosterone Effects on Systemic Insulin Metabolic Signaling” (page unavailable) reports improved skeletal-muscle glucose uptake after mineralocorticoid-receptor blockade in a rodent model. These passages support the rodent evidence, but our copy does not establish the claimed in vitro evidence for impaired insulin sensitivity in adipocytes and skeletal muscle. (LLM, conf=0.82)
Experimental — accuracy not yet measured - cites [41] E.J. Barrett, E.M. Eggleston, A.C. Inyard, H. Wang, G. Li, W. Chai, Z. Liu, The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action. Diabetologia 52(5), 752–764 (2009). https://doi.org/10.1007/s00125-009-1313-z source
The section on microvascular recruitment discusses skeletal-muscle insulin resistance and the effects of TNFα and fatty acids, but not aldosterone-induced mineralocorticoid activation. Searches of the full-text copy for “aldosterone” and “mineralocorticoid” found no passage addressing its effects on insulin sensitivity in adipocytes or skeletal muscle. (LLM, conf=0.76)
Experimental — accuracy not yet measured
- Premisecitation
Reduced insulin sensitivity has been reported in patients with primary aldosteronism when they are compared with normotensive cohorts.
“However, when compared with normotensive cohorts, reduced insulin sensitivity has been reported in PA patients [19,9,20,13,8,21,22].”
Quote in the paperSubstantial claim1 of 7 sources checked- cites [19] G. Sindelka, J. Widimsky, T. Haas, M. Prazny, J. Hilgertova, J. Skrha, Insulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment. Exp. Clin. Endocr. Diabetes 108(1), 21–25 (2000)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [9] J.M. Luther, Effects of aldosterone on insulin sensitivity and secretion. Steroids 91, 54–60 (2014). https://doi.org/10.1016/j.steroids.2014.08.016 source
Section 3.1 reports reduced insulin sensitivity in patients with primary aldosteronism in some studies, but not all. Its comparison is with hypertensive controls, not normotensive cohorts; the separate finding in normotensive subjects concerns an association between aldosterone levels and insulin sensitivity. No page number is available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [20] W. Chen, F. Li, C. He, Y. Zhu, W. Tan, Elevated prevalence of abnormal glucose metabolism in patients with primary aldosteronism: a meta-analysis. Ir. J. Med Sci. 183(2), 283–291 (2014). https://doi.org/10.1007/s11845-013-1007-x source
- cites [13] G. Colussi, C. Catena, R. Lapenna, E. Nadalini, A. Chiuch, L.A. Sechi, Insulin resistance and hyperinsulinemia are related to plasma aldosterone levels in hypertensive patients. Diabetes Care 30(9), 2349–2354 (2007). https://doi.org/10.2337/dc07-0525 source
- cites [8] G. Giacchetti, V. Ronconi, F. Turchi, L. Agostinelli, F. Mantero, S. Rilli, M. Boscaro, Aldosterone as a key mediator of the cardiometabolic syndrome in primary aldosteronism: an observational study. J. Hypertens. 25(1), 177–186 (2007). https://doi.org/10.1097/HJH.0b013e3280108e6f source
- cites [21] D. Watanabe, M. Yatabe, A. Ichihara, Evaluation of insulin sensitivity and secretion in primary aldosteronism. Clin. Exp. Hypertens. 38(7), 613–617 (2016). https://doi.org/10.1080/10641963.2016.1182176 source
- cites [22] L.M. Mosso, C.A. Carvajal, A. Maiz, E.H. Ortiz, C.R. Castillo, R.A. Artigas, C.E. Fardella, A possible association between primary aldosteronism and a lower beta-cell function. J. Hypertens. 25(10), 2125–2130 (2007). https://doi.org/10.1097/HJH.0b013e3282861fa4 source
- Premisecitation
Aldosterone stimulates hepatic glucose production by increasing gluconeogenesis.
“Aldosterone stimulates hepatic glucose production by increased gluconeogenesis [47,48].”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [47] R. Yamashita, T. Kikuchi, Y. Mori, K. Aoki, Y. Kaburagi, K. Yasuda, H. Sekihara, Aldosterone stimulates gene expression of hepatic gluconeogenic enzymes through the glucocorticoid receptor in a manner independent of the protein kinase B cascade. Endocr. J. 51(2), 243–251 (2004). https://doi.org/10.1507/endocrj.51.243 source
The Abstract reports that aldosterone increased blood glucose in mice and increased expression of gluconeogenic-enzyme genes in cultured mouse hepatocytes. The Discussion concludes that aldosterone can influence hepatic gluconeogenesis, but the paper does not establish that it increased hepatic glucose production or that increased gluconeogenesis caused the observed rise in blood glucose. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [48] G. Liu, M. Grifman, B. Keily, J.E. Chatterton, F.W. Staal, Q.X. Li, Mineralocorticoid receptor is involved in the regulation of genes responsible for hepatic glucose production. Biochem. Biophys. Res. Commun. 342(4), 1291–1296 (2006). https://doi.org/10.1016/j.bbrc.2006.02.065 source
- Premisecitation
SI measured during an oral glucose tolerance test is highly correlated with glucose disposal measured by the euglycemic-hyperinsulinemic clamp technique.
“Indeed, SI measured during an OGTT is highly correlated with glucose disposal measured during the euglycemic-hyperinsulinemic clamp technique (r = 0.70) [51].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [51] C. Cobelli, C. Dalla Man, G. Toffolo, R. Basu, A. Vella, R. Rizza, The oral minimal model method. Diabetes 63(4), 1203–1213 (2014). https://doi.org/10.2337/db13-1198 source
The “Adding a Tracer to the Oral Glucose” section reports r = 0.70 between oral-model disposal insulin sensitivity (SID) and disposal insulin sensitivity measured by a tracer-enhanced clamp. That result requires a tracer added to the oral test; the citing sentence instead presents it as a correlation for SI measured during an OGTT generally. The “Oral Glucose Minimal Model” section reports a different OGTT-versus-clamp correlation, r = 0.81, for SI. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Premisecitation
Higher post-prandial but normal nocturnal and fasting blood glucose levels contribute to high intra-day glycemic variability in patients with primary aldosteronism compared with healthy controls.
“Indeed, higher post-prandial but normal nocturnal and fasting blood glucose levels contribute to the high degree of intra-day glycemic variability in PA subjects compared with healthy controls [53].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [53] M. Han, X. Cao, C. Zhao, L. Yang, N. Yin, P. Shen, J. Zhang, F. Gao, Y. Ren, D. Liang, J. Yang, Y. Zhang, Y. Liu, Assessment of glycometabolism impairment and glucose variability using flash glucose monitoring system in patients with adrenal diseases. Front. Endocrinol. 11(759), 544752 (2020). https://doi.org/10.3389/fendo.2020.544752 source
- Findingown data
Two-hour plasma glucose concentrations during an oral glucose tolerance test were comparable between patients with primary aldosteronism and essential hypertension controls.
“Two- hour plasma glucose concentrations during an OGTT were comparable between the groups (PA: 133.7 ± 8.6 vs. EHC: 126.1 ± 8.1 mg/dL, p=0.52).”
Quote in the paperNot a substantial claim - Findingown data
Fasting plasma glucose and post-oral glucose tolerance test glucose concentrations over time did not differ significantly between patients with primary aldosteronism and essential hypertension controls.
“Fasting plasma glucose concentrations as well as post-OGTT glucose concentrations over time were not significantly different between the groups.”
Quote in the paperNot a substantial claim - Findingown data
The area under the insulin curve during an oral glucose tolerance test was significantly higher in patients with primary aldosteronism than in essential hypertension controls.
“AUCinsulin was significantly higher in PA (14748 ± 2190 vs. 8900 ± 1087 uU/mL x min, p = 0.02) (Fig 1D).”
Quote in the paperSubstantial claim - Findingown data
Hemoglobin A1c was lower in the primary aldosteronism group than in the essential hypertension control group.
“Hemoglobin A1c was lower in the PA group (5.4 ± 07 vs. 5.6 ± 0.07 %, p=0.04).”
Quote in the paperNot a substantial claim - Findingown data
The oral disposition index was similar between patients with primary aldosteronism and essential hypertension controls.
“However, oral disposition index (DI) was similar between the groups (PA: 4.77 ± 0.73 vs. EHC: 5.46 ± 0.85, p=0.42), which likely accounts for the similar glucose tolerance between the two cohorts, despite lower sensitivity.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The oral glucose minimal model's assumption of physiologic glucose kinetics throughout an OGTT holds.
- Findingown data
The area under the glucose curve during an oral glucose tolerance test was higher in patients with primary aldosteronism than in essential hypertension controls.
“However, AUCglucose during an OGTT was higher in PA (23575 ± 1059 vs. 20513 ± 1099 mg/dL x min, p = 0.05) (Fig 1B).”
Quote in the paperSubstantial claim - Findingown data
Within the primary aldosteronism cohort, QUICKI, Matsuda index, SI, HIRI, IGI, and DI did not differ significantly between patients with bilateral adrenal hyperplasia and those with aldosterone-producing adenoma.
“Within the PA cohort, QUICKI, Matsuda index, SI, HIRI, IGI, and DI were not significantly different between patients with bilateral adrenal hyperplasia and APA patients (data not shown).”
Quote in the paperNot a substantial claim- The authors state this as an assumption: The oral glucose minimal model's assumption of physiologic glucose kinetics throughout an OGTT holds.
- Findingown data
Patients with primary aldosteronism had a higher insulinogenic index than essential hypertension controls.
“The insulinogenic index (IGI), an index of β-cell function was higher in the PA cohort (PA: 1.49 ± 0.27 vs. 1.11 ± 0.21 uU/mL/mg/dL, p=0.03).”
Quote in the paperSubstantial claim - Interpretationown data
The lack of difference in disposition index between primary aldosteronism and essential hypertension controls partly explains the similar glucose tolerance between the groups.
“The DI is not different between PA and EHC, partly explaining the similar glucose tolerance between the groups.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The oral glucose minimal model's assumption of physiologic glucose kinetics throughout an OGTT holds.
- Interpretationown data
The reduced whole-body and hepatic insulin sensitivity in patients with primary aldosteronism is independent of hypertension.
“In contrast to prior studies, our findings in this report suggest that the reduced whole-body and hepatic insulin sensitivity is independent of hypertension in PA subjects.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The oral glucose minimal model's assumption of physiologic glucose kinetics throughout an OGTT holds.
- Study design and conductnone given
A limitation of the study is that plasma aldosterone and renin were not collected in the essential hypertension control group.
“A limitation of this study is that plasma aldosterone and renin were not collected in the essential hypertension control group.”
Quote in the paperNot a substantial claim - Interpretationown data
β-cells in patients with primary aldosteronism can adequately compensate for reduced insulin sensitivity by increasing insulin production.
“Our results of an increased AUCInsulin and IGI suggests that β-cells in PA can adequately compensate with increased insulin production in response to reduced insulin sensitivity.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The oral glucose minimal model's assumption of physiologic glucose kinetics throughout an OGTT holds.
- Interpretationreasoning
Findings from in vivo rodent studies and in vitro studies in β-cells, skeletal muscle, adipocytes, and hepatocytes provide a mechanistic basis for impaired insulin action and β-cell function in primary aldosteronism.
“Thus, findings from in vivo studies in rodents and in vitro studies in β-cells, skeletal muscle, adipocytes, and hepatocytes in culture provide mechanistic basis for impaired insulin action and β-cell function in PA.”
Quote in the paperSubstantial claim - Premisereasoning
It is unclear whether the hypertensive state and/or elevated aldosterone levels play a role in the reduced insulin sensitivity in primary aldosteronism.
“Based on these studies, it is unclear whether the hypertensive state and/or the elevated aldosterone levels play a role in the reduced insulin sensitivity in PA.”
Quote in the paperSubstantial claim - Premisecitation
Simple fasting-based surrogate indices do not provide a robust estimation of insulin sensitivity when used alone.
“These assessments do not provide a robust estimation of insulin sensitivity when used alone.”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [10] V. Ronconi, F. Turchi, S. Rilli, D. Di Mattia, L. Agostinelli, M. Boscaro, G: Giacchetti, Metabolic syndrome in primary aldosteronism and essential hypertension: relationship to adiponectin gene variants. Nutr. Metab. Cardiovasc. Dis. 20(2), 93–100 (2010). https://doi.org/10.1016/j.numecd.2009.03.007 source
- cites [22] L.M. Mosso, C.A. Carvajal, A. Maiz, E.H. Ortiz, C.R. Castillo, R.A. Artigas, C.E. Fardella, A possible association between primary aldosteronism and a lower beta-cell function. J. Hypertens. 25(10), 2125–2130 (2007). https://doi.org/10.1097/HJH.0b013e3282861fa4 source
- cites [5] C. Catena, R. Lapenna, S. Baroselli, E. Nadalini, G. Colussi, M. Novello, G. Favret, A. Melis, A. Cavarape, L.A. Sechi, Insulin sensitivity in patients with primary aldosteronism: a follow-up study. J. Clin. Endocrinol. Metab. 91(9), 3457–3463 (2006). https://doi.org/10.1210/jc.2006-0736 source
- cites [13] G. Colussi, C. Catena, R. Lapenna, E. Nadalini, A. Chiuch, L.A. Sechi, Insulin resistance and hyperinsulinemia are related to plasma aldosterone levels in hypertensive patients. Diabetes Care 30(9), 2349–2354 (2007). https://doi.org/10.2337/dc07-0525 source
- Premisecitation
In a subset of patients, insulin sensitivity assessed by the euglycemic hyperinsulinemic clamp technique was comparable between primary aldosteronism and essential hypertension controls.
“Insulin sensitivity as assessed by the euglycemic hyperinsulinemic clamp technique in a subset of these patients was comparable between PA and EHC [5].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [5] C. Catena, R. Lapenna, S. Baroselli, E. Nadalini, G. Colussi, M. Novello, G. Favret, A. Melis, A. Cavarape, L.A. Sechi, Insulin sensitivity in patients with primary aldosteronism: a follow-up study. J. Clin. Endocrinol. Metab. 91(9), 3457–3463 (2006). https://doi.org/10.1210/jc.2006-0736 source
- Premisecitation
A meta-analysis and systematic review by Chen et al. found that patients with primary aldosteronism have an increased risk of impaired glucose homeostasis compared with essential hypertensives.
“Chen et al. conducted a meta-analysis and systematic review and found that PA patients are at an increased risk for impaired glucose homeostasis (e.g. IFG, IGT, T2D) as compared to essential hypertensives [20].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] W. Chen, F. Li, C. He, Y. Zhu, W. Tan, Elevated prevalence of abnormal glucose metabolism in patients with primary aldosteronism: a meta-analysis. Ir. J. Med Sci. 183(2), 283–291 (2014). https://doi.org/10.1007/s11845-013-1007-x source
- Premisecitation
Multiple studies examining insulin sensitivity in primary aldosteronism used normotensive controls, making hypertension a confounding variable.
“Multiple studies examining insulin sensitivity in PA subjects used normotensive individuals as controls, rendering hypertension a confounding variable [24,19].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [24] M. Ishimori, N. Takeda, S. Okumura, T. Murai, H. Inouye, K. Yasuda, Increased insulin sensitivity in patients with aldosterone producing adenoma. Clin. Endocrinol. 41(4), 433–438 (1994). https://doi.org/10.1111/j.1365-2265.1994.tb02573.x source
- cites [19] G. Sindelka, J. Widimsky, T. Haas, M. Prazny, J. Hilgertova, J. Skrha, Insulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment. Exp. Clin. Endocr. Diabetes 108(1), 21–25 (2000)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Classified as probably not a substantial claim. 11
- May combine two claims. 16
- The quote only partly states this claim. 1
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationA recently published study found that patients with primary aldosteronism had reduced insulin secretion, increased insulin clearance and insulin sensitivity, and unchanged disposition index using hyperglycemic and euglycemic-hyperinsulinemic clamps.
“In a recently published study, patients with PA had reduced insulin secretion, increased insulin clearance and insulin sensitivity, and unchanged DI using hyperglycemic and euglycemic-hyperinsulinemic clamps [52].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [52] G.K. Adler, G.R. Murray, A.F. Turcu, H. Nian, C. Yu, C.C. Solorzano, R. Manning, D. Peng, J.M. Luther, Primary aldosteronism decreases insulin secretion and increases insulin clearance in humans. Hypertension 75(5), 1251–1259 (2020). https://doi.org/10.1161/HYPERTENSIONAHA.119.13922 source
Classified as probably not a substantial claim.
Premisenone givenThe effects of hyperaldosteronism on insulin sensitivity and β-cell function are unclear.
“However, the effects of hyperaldosteronism on insulin sensitivity and β-cell function are unclear.”
Quote in the paperSubstantial claim1 of 10 sources checked- cites [19] G. Sindelka, J. Widimsky, T. Haas, M. Prazny, J. Hilgertova, J. Skrha, Insulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment. Exp. Clin. Endocr. Diabetes 108(1), 21–25 (2000)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [9] J.M. Luther, Effects of aldosterone on insulin sensitivity and secretion. Steroids 91, 54–60 (2014). https://doi.org/10.1016/j.steroids.2014.08.016 source
- cites [20] W. Chen, F. Li, C. He, Y. Zhu, W. Tan, Elevated prevalence of abnormal glucose metabolism in patients with primary aldosteronism: a meta-analysis. Ir. J. Med Sci. 183(2), 283–291 (2014). https://doi.org/10.1007/s11845-013-1007-x source
- cites [13] G. Colussi, C. Catena, R. Lapenna, E. Nadalini, A. Chiuch, L.A. Sechi, Insulin resistance and hyperinsulinemia are related to plasma aldosterone levels in hypertensive patients. Diabetes Care 30(9), 2349–2354 (2007). https://doi.org/10.2337/dc07-0525 source
- cites [8] G. Giacchetti, V. Ronconi, F. Turchi, L. Agostinelli, F. Mantero, S. Rilli, M. Boscaro, Aldosterone as a key mediator of the cardiometabolic syndrome in primary aldosteronism: an observational study. J. Hypertens. 25(1), 177–186 (2007). https://doi.org/10.1097/HJH.0b013e3280108e6f source
- cites [21] D. Watanabe, M. Yatabe, A. Ichihara, Evaluation of insulin sensitivity and secretion in primary aldosteronism. Clin. Exp. Hypertens. 38(7), 613–617 (2016). https://doi.org/10.1080/10641963.2016.1182176 source
- cites [22] L.M. Mosso, C.A. Carvajal, A. Maiz, E.H. Ortiz, C.R. Castillo, R.A. Artigas, C.E. Fardella, A possible association between primary aldosteronism and a lower beta-cell function. J. Hypertens. 25(10), 2125–2130 (2007). https://doi.org/10.1097/HJH.0b013e3282861fa4 source
- cites [4] E. Fischer, C. Adolf, A. Pallauf, C. Then, M. Bidlingmaier, F. Beuschlein, J. Seissler, M. Reincke, Aldosterone excess impairs first phase insulin secretion in primary aldosteronism. J. Clin. Endocrinol. Metab. 98(6), 2513–2520 (2013). https://doi.org/10.1210/jc.2012-3934 source
- cites [23] J. Widimsky, B. Strauch, G. Sindelka, J. Skrha, Can primary hyperaldosteronism be considered as a specific form of diabetes mellitus? Physiol. Res. 50(6), 603–607 (2001)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [24] M. Ishimori, N. Takeda, S. Okumura, T. Murai, H. Inouye, K. Yasuda, Increased insulin sensitivity in patients with aldosterone producing adenoma. Clin. Endocrinol. 41(4), 433–438 (1994). https://doi.org/10.1111/j.1365-2265.1994.tb02573.x source
Classified as probably not a substantial claim.
PremisecitationThe oral glucose minimal model provides a measure of insulin sensitivity during an oral glucose tolerance test.
“Developed by Cobelli et al., the oral glucose minimal model provides a measure of insulin sensitivity during an OGTT.”
Quote in the paperSubstantial claim1 of 3 sources checked- cites Cobelli et al.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [28] C. Dalla Man, A. Caumo, C. Cobelli, The oral glucose minimal model: estimation of insulin sensitivity from a meal test. IEEE Trans. Biomed. Eng. 49(5), 419–429 (2002). https://doi.org/10.1109/10.995680 source
- cites [29] A. Caumo, R.N. Bergman, C. Cobelli, Insulin sensitivity from meal tolerance tests in normal subjects: a minimal model index. J. Clin. Endocrinol. Metab. 85(11), 4396–4402 (2000). https://doi.org/10.1210/jcem.85.11.6982 source
- The authors state this as an assumption: The oral glucose minimal model's assumption of physiologic glucose kinetics throughout an OGTT holds.
May combine two claims. The quote only partly states this claim.
Findingown dataPatients with primary aldosteronism had lower whole-body insulin sensitivity than essential hypertension controls, as shown by lower QUICKI, Matsuda Index, and SI values after adjustment for age, sex, BMI, and mean arterial pressure.
“PA individuals were less insulin sensitive compared to EHC subjects (Quantitative insulin sensitivity check index [QUICKI]: 0.340 ± 0.006 vs. 0.374 ± 0.013, p<0.001; Matsuda Index: 4.14 ± 0.49 vs. 7.87 ± 1.42, p <0.001; SI: 11.45 ± 4.85 vs. 21.23 ± 6.11 dl/kg/min per μU/ml, p=0.02).”
Quote in the paperSubstantial claim- The authors state this as an assumption: The oral glucose minimal model's assumption of physiologic glucose kinetics throughout an OGTT holds.
May combine two claims.
Findingown dataPatients with primary aldosteronism had a higher hepatic insulin resistance index than essential hypertension controls, indicating lower liver insulin sensitivity.
“The hepatic insulin resistance index (HIRI) was higher in PA subjects (PA: 5.61 ± 1.01 vs. EHC: 4.13 ± 0.61, p=0.002).”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataPatients with primary aldosteronism have lower insulin sensitivity together with appropriately compensated β-cell function.
“In summary, insulin sensitivity is significantly lower in PA with an appropriately compensated β-cell function.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The oral glucose minimal model's assumption of physiologic glucose kinetics throughout an OGTT holds.
May combine two claims.
Interpretationown dataExcess aldosterone and/or other steroids in primary aldosteronism may negatively affect insulin action without adversely impacting β-cell function.
“These results suggest that excess aldosterone and/or other steroids in the context of PA may negatively affect insulin action without adversely impacting β-cell function.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The oral glucose minimal model's assumption of physiologic glucose kinetics throughout an OGTT holds.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe cross-sectional study design was limited by its observational nature and small sample size.
“Lastly, the cross-sectional study design was limited by its observational nature and small sample size.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenMeasures of insulin sensitivity and β-cell function were adjusted for age, sex, BMI, and mean arterial pressure before comparison between groups.
“Age, sex, BMI, and mean arterial pressure adjusted measures of insulin sensitivity and β-cell function were compared between the groups.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductown dataPatients with primary aldosteronism and essential hypertension controls had comparable metabolic profiles, with no significant differences in fasting glucose or insulin concentrations.
“PA and EHC had comparable metabolic profiles, with no significant differences in fasting glucose or insulin concentrations.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThe study did not assess 24-hour plasma glucose levels and therefore cannot explain the lower A1C levels in patients with primary aldosteronism.
“We did not assess 24-hr plasma glucose levels in our patients and thus cannot explain the slightly but significantly lower levels of A1C in PA subjects.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataPatients with primary aldosteronism have reduced insulin sensitivity with preserved β-cell function that maintains glucose tolerance.
“Our results suggest that PA patients have reduced insulin sensitivity with preserved β-cell function in order to maintain glucose tolerance.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The oral glucose minimal model's assumption of physiologic glucose kinetics throughout an OGTT holds.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenThe study assessed insulin sensitivity thoroughly using both surrogate indices and an oral glucose minimal model analysis.
“This study was thorough in its assessment of insulin sensitivity via both surrogate indices of insulin sensitivity and an oral glucose minimal model analysis.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenA notable strength of the study was comparing patients with primary aldosteronism against essential hypertensive controls rather than normotensive controls.
“A notable strength in this study was its assessment of patients with PA against essential hypertensive, rather than normotensive controls.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThere were no follow-up metabolic assessments after treatment in the primary aldosteronism group.
“Further, there were no follow-up metabolic assessments following treatment in the PA group.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataPatients with primary aldosteronism and essential hypertension controls were similar in age, sex, BMI, and systolic and diastolic blood pressure.
“PA and EHC were similar in age, sex, BMI, and systolic and diastolic blood pressure.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationMany prior studies were conducted in Europe or Japan and are not easily generalized to a more diverse and heterogeneous US population.
“Lastly, many of these studies were conducted in Europe or Japan [5,24,4,19,23] and thus not easily generalized to a more diverse and heterogenous US population.”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [5] C. Catena, R. Lapenna, S. Baroselli, E. Nadalini, G. Colussi, M. Novello, G. Favret, A. Melis, A. Cavarape, L.A. Sechi, Insulin sensitivity in patients with primary aldosteronism: a follow-up study. J. Clin. Endocrinol. Metab. 91(9), 3457–3463 (2006). https://doi.org/10.1210/jc.2006-0736 source
- cites [24] M. Ishimori, N. Takeda, S. Okumura, T. Murai, H. Inouye, K. Yasuda, Increased insulin sensitivity in patients with aldosterone producing adenoma. Clin. Endocrinol. 41(4), 433–438 (1994). https://doi.org/10.1111/j.1365-2265.1994.tb02573.x source
- cites [4] E. Fischer, C. Adolf, A. Pallauf, C. Then, M. Bidlingmaier, F. Beuschlein, J. Seissler, M. Reincke, Aldosterone excess impairs first phase insulin secretion in primary aldosteronism. J. Clin. Endocrinol. Metab. 98(6), 2513–2520 (2013). https://doi.org/10.1210/jc.2012-3934 source
- cites [19] G. Sindelka, J. Widimsky, T. Haas, M. Prazny, J. Hilgertova, J. Skrha, Insulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment. Exp. Clin. Endocr. Diabetes 108(1), 21–25 (2000)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [23] J. Widimsky, B. Strauch, G. Sindelka, J. Skrha, Can primary hyperaldosteronism be considered as a specific form of diabetes mellitus? Physiol. Res. 50(6), 603–607 (2001)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationWatanabe et al. suggest a hypokalemia-independent impairment of early-phase insulin response to glucose in primary aldosteronism.
“Additionally, Watanabe et al. suggest a hypokalemia-independent impairment of early-phase insulin response to glucose in PA.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] D. Watanabe, M. Yatabe, A. Ichihara, Evaluation of insulin sensitivity and secretion in primary aldosteronism. Clin. Exp. Hypertens. 38(7), 613–617 (2016). https://doi.org/10.1080/10641963.2016.1182176 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAnother study found an increased first-phase insulin response after unilateral adrenalectomy in nine patients with primary aldosteronism, suggesting a direct negative effect of aldosterone on β-cell function.
“Another study demonstrated an increased first-phase insulin response following unilateral adrenalectomy in nine PA patients, suggesting a direct negative effect of aldosterone on β-cell function [4].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4] E. Fischer, C. Adolf, A. Pallauf, C. Then, M. Bidlingmaier, F. Beuschlein, J. Seissler, M. Reincke, Aldosterone excess impairs first phase insulin secretion in primary aldosteronism. J. Clin. Endocrinol. Metab. 98(6), 2513–2520 (2013). https://doi.org/10.1210/jc.2012-3934 source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMosso et al. found reduced insulin secretion, assessed by HOMA-β, in patients with primary aldosteronism compared with essential hypertension controls.
“Mosso et al. demonstrated reduced insulin secretion, as assessed by HOMA-β, in PA compared to EHC [22].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22] L.M. Mosso, C.A. Carvajal, A. Maiz, E.H. Ortiz, C.R. Castillo, R.A. Artigas, C.E. Fardella, A possible association between primary aldosteronism and a lower beta-cell function. J. Hypertens. 25(10), 2125–2130 (2007). https://doi.org/10.1097/HJH.0b013e3282861fa4 source
May combine two claims.
PremisecitationAldosterone-induced hypokalemia was originally proposed to affect insulin sensitivity, but normalization of potassium levels or potassium depletion did not significantly modulate tissue insulin sensitivity.
“Lastly, aldosterone-induced hypokalemia was originally proposed to affect insulin sensitivity, but normalization of potassium levels or potassium depletion did not significantly modulate tissue insulin sensitivity [49,3].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [49] J.W. Rowe, J.D. Tobin, R.M. Rosa, R. Andres, Effect of experimental potassium deficiency on glucose and insulin metabolism. Metabolism 29(6), 498–502 (1980). https://doi.org/10.1016/0026-0495(80)90074-8 source
- cites [3] J.W. Conn, Hypertension, the potassium ion and impaired carbohydrate tolerance. N. Engl. J. Med. 273(21), 1135–1143 (1965). https://doi.org/10.1056/NEJM196511182732106 source
May combine two claims.
PremisecitationCatena et al. found that patients with primary aldosteronism were insulin resistant compared with normotensive controls, but hypertensive patients were more insulin resistant than those with primary aldosteronism.
“They demonstrated that while PA patients were insulin resistant when compared with normotensive controls, hypertensive patients were more insulin-resistant than PA subjects [5].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [5] C. Catena, R. Lapenna, S. Baroselli, E. Nadalini, G. Colussi, M. Novello, G. Favret, A. Melis, A. Cavarape, L.A. Sechi, Insulin sensitivity in patients with primary aldosteronism: a follow-up study. J. Clin. Endocrinol. Metab. 91(9), 3457–3463 (2006). https://doi.org/10.1210/jc.2006-0736 source
May combine two claims.
PremisecitationHIRI predicts and correlates well with hepatic insulin resistance as measured by the reference glucose clamp technique.
“We and others have previously shown that HIRI predicts and correlates well with hepatic insulin resistance as measured with the reference glucose clamp technique (r=0.49) [32].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [32] R. Muniyappa, S.H. Tella, S. Sortur, R. Mszar, S. Grewal, B.S. Abel, S. Auh, D.C. Chang, J. Krakoff, M.C. Skarulis, Predictive accuracy of surrogate indices for hepatic and skeletal muscle insulin sensitivity. J. Endocr. Soc. 3(1), 108–118 (2019). https://doi.org/10.1210/js.2018-00206 source
May combine two claims.
PremisecitationHypertension is an insulin-resistant state, and primary aldosteronism is frequently associated with hypertension.
“First, hypertension is an insulin-resistant state and PA is frequently associated with hypertension [25,26].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [25] L.A. Sechi, A. Melis, R. Tedde, Insulin hypersecretion: a distinctive feature between essential and secondary hypertension. Metabolism 41(11), 1261–1266 (1992). https://doi.org/10.1016/0026-0495(92)90019-7 source
- cites [26] G.M. Reaven, Insulin resistance/compensatory hyperinsulinemia, essential hypertension, and cardiovascular disease. J. Clin. Endocrinol. Metab. 88(6), 2399–2403 (2003). https://doi.org/10.1210/jc.2003-030087 source
The authors state this as an assumption.
The oral glucose minimal model's assumption of physiologic glucose kinetics throughout an OGTT holds.
“This model is derived from an assumption of physiologic glucose kinetics throughout an OGTT.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
SI is reported with different units in the abstract and results
MinorThe abstract omits the 10−4 scale factor included with SI in the Results. That factor changes the stated magnitude of the same SI values by 10,000-fold.
“SI: 11.45 ± 4.85 vs. 21.23 ± 6.11 dl/kg/min per μU/ml, p=0.02”
“SI (11.45 ± 4.85 vs. 21.23 ± 6.11 10−4.dl/kg/min per μU/ml, p=0.02)”
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“As described previously, the Matsuda index is an OGTT-derived composite estimate of whole-body insulin sensitivity [31].”
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“In a recently published study, patients with PA had reduced insulin secretion, increased insulin clearance and insulin sensitivity, and unchanged DI using hyperglycemic and euglycemic–hyperinsulinemic clamps [52].”
BackgroundThe prevalence of metabolic syndrome and its components in two main types of primary aldosteronism
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Impact of excess aldosterone on glucose homeostasis in adult male rat
Selvaraj, J., Muthusamy, T., Srinivasan, C., & Balasubramanian, K. (2009) · Clinica Chimica Acta · doi:10.1016/j.cca.2009.06.030 · Cited by 38 · cited 1× · see citing works
“inflammatory cytokines/adipokines [9, 18].”
Santos, J. L., Yévenes, I., Cataldo, L. R., Morales, M., Galgani, J., Arancibia, C., Vega, J., Olmos, P., Flores, M., Valderas, J., et al. (2015) · Journal of physiology and biochemistry · doi:10.1007/s13105-015-0458-0 · Cited by 34 · cited 1× · see citing works
“secretion and insulin sensitivity derived from an OGTT: DIoral=AUCInsulin/AUCGlucose × SI [35].”
MethodCan primary hyperaldosteronism be considered as a specific form of diabetes mellitus?
Widimsky, J., Jr., Štrauch, B., Šindelka, G., & Škrha, J. (2001) · Physiological Research · doi:10.33549/physiolres.930123 · Cited by 33 · cited 2× · see citing works
“studies suggest increased or unchanged insulin sensitivity [4, 23, 24].”
BackgroundLeptin and Adiponectin mRNA Expression From the Adipose Tissue Surrounding the Adrenal Neoplasia
Letizia, C., Petramala, L., Gioia, C. R. T. D., Chiappetta, C., Zinnamosca, L., Marinelli, C., Iannucci, G., Ciardi, A., Toma, G. D., & Iacobellis, G. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2274 · Cited by 32 · see citing works
Evaluation and Management of Primary Hyperaldosteronism
Lee, F. T., & Elaraj, D. M. (2019) · Surgical Clinics of North America · doi:10.1016/j.suc.2019.04.010 · Cited by 32 · cited 1× · see citing works
“PA patients frequently experience hypernatremia, hypokalemia, and secondary hypertension [1, 4].”
BackgroundLiu, G., Grifman, M., Keily, B., Chatterton, J. E., Staal, F.-W., & Li, Q.-X. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.02.065 · Cited by 28 · cited 1× · see citing works
“Aldosterone stimulates hepatic glucose production by increased gluconeogenesis [47, 48].”
BackgroundPrimary Aldosteronism: Cardiovascular Outcomes Pre- and Post-treatment
Hundemer, G. L. (2019) · Current Cardiology Reports · doi:10.1007/s11886-019-1185-x · Cited by 27 · see citing works
Increased insulin sensitivity in patients with aldosterone producing adenoma
Ishimori, M., Takeda, N., Okumura, S., Murai, T., Inouye, H., & Yasuda, K. (1994) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1994.tb02573.x · Cited by 24 · cited 3× · see citing works
“studies suggest increased or unchanged insulin sensitivity [4, 23, 24].”
BackgroundEvaluation of insulin sensitivity and secretion in primary aldosteronism
Watanabe, D., Yatabe, M., & Ichihara, A. (2016) · Clinical and Experimental Hypertension · doi:10.1080/10641963.2016.1182176 · Cited by 16 · cited 1× · see citing works
“While HOMA-β between their PA and EHC cohorts were comparable, IGI was significantly reduced in PA [21].”
BackgroundPredictive Accuracy of Surrogate Indices for Hepatic and Skeletal Muscle Insulin Sensitivity
Muniyappa, R., Tella, S. H., Sortur, S., Mszar, R., Grewal, S., Abel, B. S., Auh, S., Chang, D. C., Krakoff, J., & Skarulis, M. C. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2018-00206 · Cited by 16 · see citing works
Self-citationUtzschneider, K. M., Prigeon, R. L., Faulenbach, M. V., et al. (2009) · Diabetes Care · doi:10.2337/dc09-0729 · Cited by 10 · see citing works
Han, M., Cao, X., Zhao, C., Yang, L., Yin, N., Shen, P., Zhang, J., Gao, F., Ren, Y., Liang, D., et al. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.544752 · Cited by 10 · cited 1× · see citing works
“degree of intra-day glycemic variability in PA subjects compared with healthy controls [53].”
Background
Flagged first, then by citations
1 of the 54 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- G. Giacchetti, V. Ronconi, F. Turchi, L. Agostinelli, F. Mantero, S. Rilli, M. Boscaro, Aldosterone as a key mediator of the cardiometabolic syndrome in primary aldosteronism: an observational study. J. Hypertens. 25(1), 177–186 (2007). https://doi.org/10.1097/HJH.0b013e3280108e6f · DOI · Paper page
Cited by
Sorted by citations
The Effect of Aldosterone on Cardiorenal and Metabolic Systems
Otsuka, H., Abe, M., & Kobayashi, H. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065370 · Cited by 68 · see citing works
The role of dietary salt in metabolism and energy balance: Insights beyond cardiovascular disease
Wu, Q., Burley, G., Li, L., Lin, S., & Shi, Y. (2023) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14980 · Cited by 57 · see citing works
Wang, W., Wu, T.-H., Er, L., Huang, C., Tu, K., Fan, K., Tsai, C., Wang, S., Wu, C.-Y., Huang, S.-H., et al. (2024) · Hypertension Research · doi:10.1038/s41440-023-01538-x · Cited by 17 · see citing works
Manosroi, W., Atthakomol, P., Watanawittawas, P., & Buranapin, S. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.870047 · Cited by 14 · see citing works
Aldosterone, mitochondria and regulation of cardiovascular metabolic disease
Tsai, C., Chen, Z., Lee, B., Liao, C., Chang, Y., Tsai, Y.-R., Chou, C., Wu, V., Hung, C., & Lin, Y. (2024) · Journal of Endocrinology · doi:10.1530/joe-23-0350 · Cited by 11 · see citing works
Sun, K., Zhou, C., Gong, M., Zhang, Y., Jiang, Y., & Song, W. (2024) · Journal of Clinical Hypertension · doi:10.1111/jch.14873 · Cited by 8 · see citing works
“10,35 26 providing the prevalence Excess aldosterone could lead a reduction in insulin secretion in Kwak andcolleagues, 36 whileGrewalandcolleagues 37 concludedthatinsulin sensitivity was lower in PA and β -cell function was not impaired.”
BackgroundImpact of Primary Aldosteronism in Resistant Hypertension
Stavropoulos, K., Imprialos, K. P., Patoulias, D., Katsimardou, A., & Doumas, M. N. (2022) · Current Hypertension Reports · doi:10.1007/s11906-022-01190-9 · Cited by 6 · see citing works
Ohira, M., Kawagoe, N., Kameyama, C., Kondou, Y., Igarashi, M., & Ueshiba, H. (2025) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-025-01706-8 · Cited by 5 · see citing works
Diagnostic value of the fractional excretion of urine potassium for primary aldosteronism
Yuan, H., Wang, B., Yang, Y., et al. (2023) · Annals of Translational Medicine · doi:10.21037/atm-22-6410 · Cited by 5 · see citing works
“PA can be traced to severe glucose metabolism disorders (6).”
Xin, Y., Yin, Y., Zhu, L., Wang, Y., Wu, T., Xu, J., & Zang, L. (2025) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2025.112160 · Cited by 2 · see citing works
Liao, Y., Zuo, M., Zhu, Y., Xu, T., Tang, J., Fan, L., & Zhang, N. (2025) · Discover Oncology · doi:10.1007/s12672-025-02108-y · Cited by 1 · see citing works
“High levels of aldosterone can directly inhibit the insulin-secreting function of pancreatic β-cells, leading to a decrease in insulin secretion and an inability to effectively regulate blood glucose, which in turn triggers diabetes [27].”
Aldosterone induced by chronic stress promotes pancreatic steatosis in young male rats
Pérez-Sánchez, E., Sánchez‐Solís, C. N., Morimoto, S., Corona‐Pérez, A., Martı́nez–Gómez, M., Rodríguez‐Antolín, J., Cuevas‐Romero, E., & Nicolás‐Toledo, L. (2026) · Cell and Tissue Research · doi:10.1007/s00441-025-04029-2 · Cited by 1 · see citing works
“During pancreatitis, tumor necrosis factor-alpha (TNF-α) released by exocrine acinar cells induces apoptosis Eliut Pérez-Sánchez and Cristhian Neftaly Sánchez-Solís contributed equally to this work.”
Unveiling the role of aldosterone in metabolic dysfunction–associated steatotic liver disease
Hernández‐Rubio, A., Julián, M. T., Valassi, E., Alonso, N., & Puig‐Domingo, M. (2026) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-026-10056-3 · Cited by 1 · see citing works
“The most common cause of secondary hypertension is PA, which is associated with cardiovascular and renal complications, as well as metabolic disturbances such as insulin resistance and adipose tissue dysfunction [67, 68].”
Honour, J. W. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-818124-9.00005-x
Diabetes in Hypersecreting Endocrine Disorders
Vaag, A. A., Hanley, N. A., & Kistorp, C. (2024) · doi:10.1002/9781119697473.ch22
Sun, Z., & Liu, W. (2025) · SAGE Open Medicine · doi:10.1177/20503121251324797
Yu, F., Wu, S., Qin, L.-H., et al. (2025) · World Chinese Journal of Digestology · doi:10.11569/wcjd.v33.i7.553
Ma, X., Lin, X., Liu, N., et al. (2026) · Endocrine · doi:10.1007/s12020-025-04492-5
Beyond aldosterone and renin: emerging biomarkers for diagnosing and subtyping primary aldosteronism
Libianto, R., Uniacke, C. L., Fuller, P. J., Young, M. J., & Yang, J. (2026) · Endocrine Reviews · doi:10.1210/endrev/bnag016
Cardiovascular and Metabolic Consequences of Inherited and Acquired Adrenal Disorders
Bai, Y., & Chen, X. (2026) · IntechOpen eBooks · doi:10.5772/intechopen.1016747
- Authors
- Grewal, S., Fosam, A., Chalk, L., Deven, A., Suzuki, M., Correa, R. R., Blau, J. E., Demidowich, A. P., Stratakis, C. A., & Muniyappa, R.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Muniyappa, Ranganath
- ORCID
- Venue
- Endocrine
- Published
- 2021-01-18
- Volume
- 72
- Issue
- 1
- Pages
- 96-103
- ISSN
- 0969-711X (ISSN-L)
- 1355-008X
- 1559-0100
- PMC
- PMC8087621
- OpenAlex
- W3123162996
- Semantic Scholar
- 4d4ec6dbe63278c171dd620b0f6a354ef6d367fd
- Cited by
- 20
- References
- 54
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 2
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Intramural Program NIDDK/NICHD
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- primary aldosteronism, insulin sensitivity, insulin resistance, beta-cell function, hyperaldosteronism, insulinogenic index, oral disposition index, essential hypertension, dysglycemia, oral glucose tolerance test
- MeSH terms
- Blood Glucose, Cross-Sectional Studies, Glucose Tolerance Test, Humans, Hyperaldosteronism, Insulin, Insulin Resistance, Insulin-Secreting Cells
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