Resistance to Insulin in Patients with Gitelman Syndrome and a Subtle Intermediate Phenotype in Heterozygous Carriers: A Cross-Sectional Study

被引：40

作者：

Blanchard, Anne ^{[1
,5
,6
]}

Vallet, Marion ^{[7
]}

Dubourg, Laurence ^{[8
]}

Hureaux, Marguerite ^{[2
,5
]}

Allard, Julien ^{[9
,10
]}

Haymann, Jean-Philippe ^{[11
,12
,13
]}

de la Faille, Renaud ^{[14
]}

Arnoux, Armelle ^{[3
,6
]}

Dinut, Aurelie ^{[6
]}

Bergerot, Damien ^{[1
,6
]}

Becker, Pierre-Hadrien ^{[15
]}

Courand, Pierre-Yves ^{[1
,16
]}

Baron, Stephanie ^{[4
,5
]}

Houillier, Pascal ^{[4
,5
]}

Tack, Ivan ^{[7
]}

Devuyst, Olivier ^{[17
,18
]}

Jeunemaitre, Xavier ^{[2
,5
,19
]}

Azizi, Michel ^{[1
,5
,6
]}

Vargas-Poussou, Rosa ^{[2
]}

机构：

[1] Hop Europeen Georges Pompidou, AP HP, Clin Invest Ctr, Paris, France

[2] Hop Europeen Georges Pompidou, AP HP, Dept Genet, Paris, France

[3] Hop Europeen Georges Pompidou, AP HP, Clin Res Unit, Paris, France

[4] Hop Europeen Georges Pompidou, AP HP, Dept Physiol Funct Invest, Paris, France

[5] Paris Descartes Univ, Fac Med, Sorbonne Paris Cite, Paris, France

[6] Inst Natl Sante & Rech Med, Clin Invest Ctr 1418, Paris, France

[7] Univ Paul Sabatier, CHU Toulouse, Dept Physiol Funct Invest, Toulouse, France

[8] Hosp Civils Lyon, Hosp Edouard Herriot, Dept Physiol Funct Invest, Lyon, France

[9] CHU Limoges, Hop Dupuytren, Dept Nephrol, Limoges, France

[10] Inst Natl Sante & Rech Med, Clin Invest Ctr 1435, Limoges, France

[11] Hop Tenon, AP HP, Dept Physiol Funct Invest, Paris, France

[12] Univ Paris 06, Fac Med, Paris, France

[13] Inst Natl Sante & Rech Med, Unite Mixte Rech S 1155, Paris, France

[14] CHU Bordeaux, Dept Nephrol, Bordeaux, France

[15] Hop Bicetre, AP HP, Dept Biochem, Le Kremlin Bicetre, France

[16] Hosp Civils Lyon, Croix Rousse & Lyon Sud Hosp, Dept Cardiol, Lyon, France

[17] Univ Zurich, Inst Physiol, Zurich, Switzerland

[18] Catholic Univ Louvain, Med Sch, Div Nephrol, Brussels, Belgium

[19] Inst Natl Sante & Rech Med, Unite Mixte Rech 970, Paris, France

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2019年 / 30卷 / 08期

关键词：

SODIUM-CHLORIDE COTRANSPORTER; GLUCOSE-TOLERANCE; CHINESE PATIENTS; BLOOD-PRESSURE; FOLLOW-UP; MUTATIONS; HYPERTENSION; ASSOCIATION; HYPOKALEMIA; SENSITIVITY;

D O I：

10.1681/ASN.2019010031

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Background Gitelman syndrome is a salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive sodium-chloride cotransporter. Previous studies suggested an intermediate phenotype for heterozygous carriers. Methods To evaluate the phenotype of heterozygous carriers of pathogenic SLC12A3 mutations, we performed a cross-sectional study of patients with Gitelman syndrome, heterozygous carriers, and healthy noncarriers. Participants measured their BP at home for three consecutive days before hospital admission for blood and urine sampling and an oral glucose tolerance test. Results We enrolled 242 participants, aged 18-75 years, including 81 heterozygous carriers, 82 healthy noncarriers, and 79 patients with Gitelman syndrome. The three groups had similar age, sex ratio, and body mass index. Compared with healthy noncarriers, heterozygous carriers showed significantly higher serumcalcium concentration (P=0.01) and a trend for higher plasma aldosterone (P=0.06), but measures of home BP, plasma and urine electrolytes, renin, parathyroid hormone, vitamin D, and response to oral glucose tolerance testing were similar. Patients with Gitelman syndrome had lower systolic BP and higher heart rate than noncarriers and heterozygote carriers; they also had significantly higher fasting serum glucose concentration, higher levels of markers of insulin resistance, and a three-fold higher sensitivity to overweight. According to oral glucose tolerance testing, approximately 14% of patients with Gitelman syndrome were prediabetic, compared with 5% of heterozygous carriers and 4% of healthy noncarriers. Conclusions Heterozygous carriers had a weak intermediate phenotype, between that of healthy noncarriers and patients with Gitelman syndrome. Moreover, the latter are at risk for development of type 2 diabetes, indicating the heightened importance of body weight control in these patients.

引用

页码：1533 / 1544

页数：12

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