Circulatory and renal consequences of pregnancy in diabetic NOD mice

Abstract

Objectives-Women with diabetes have elevated gestational risks for severe hemodynamic complications, including preeclampsia in mid-to late pregnancy. This study employed continuous, chronic radiotelemetry to compare the hemodynamic patterns in non-obese diabetic (NOD) mice who were overtly diabetic or normoglycemic throughout gestation. We hypothesized that overtly diabetic, pregnant NOD mice would develop gestational hypertension and provide understanding of mechanisms in progression of this pathology.Study Design-Telemeter-implanted, age-matched NOD females with and without diabetes were assessed for six hemodynamic parameters (mean, systolic, diastolic, pulse pressures, heart rate and activity) prior to mating, over pregnancy and over a 72 hr post-partum interval. Urinalysis, serum biochemistry and renal histopathology were also conducted.Results-Pregnant, normoglycemic NOD mice had a hemodynamic profile similar to other inbred strains, despite insulitis. This pattern was characterized by an interval of pre-implantation stability, post implantation decline in arterial pressure to mid gestation, and then a rebound to prepregnancy baseline during later gestation. Overtly diabetic NOD mice had a blood pressure profile that was normal until mid-gestation then become mildly hypotensive (−7mmHg, P<0.05), severely bradycardic (−80bpm, P<0.01) and showed signs of acute kidney injury. Pups born to diabetic dams were viable but growth restricted, despite their mothers' failing health, which did not rebound post-partum (−10% pre-pregnancy pressure and HR, P<0.05).Conclusions-Pregnancy accelerates circulatory and renal pathologies in overtly diabetic NOD mice and is characterized by depressed arterial pressure from mid-gestation and birth of growth 45 restricted offspring. KeywordsType 1 Diabetes Mellitus; Pregnancy; Radiotelemetry; Hemodynamics Correspondence: Anne Croy, Department of Biomedical and Molecular Sciences, Room 924 Botterell Hall, 18 Stuart Street, Queen's University, Kingston, Ontario, Canada K7L 3N6, Fax: 1-613-533-2022, Telephone: 1-613-533-2859 CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptCardiovascular complications are common and progressive in Type 1 Diabetes Mellitus (T1DM), often leading to significant morbidity and death. Pregnancy has been described as a physiological stressor and early predictor of cardiovascular disease when outcomes are abnormal [1]. Women with pre-existing diabetes (autoimmune and non-insulin-dependent diabetes mellitus) are considered high-risk obstetrical patients with significantly increased risks for complications; including worsening of pre-existing diabetic sequelae (diabetic nephropathy, retinopathy and altered glycemic control), pregnancy-induced hypertension, preeclampsia and thromboembolic events [2][3][4][5]. Severity of the pre-existing diabetic disease status rather than glycemic control is used to stratify risk for these women. Risks for the fetuses and children of mothers with diabetes include congenital defects, growth restricti...

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Proteomic analyses of Urine Exosomes reveal New Biomarkers of Diabetes in Pregnancy

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