adrenomedullin and Prediabetic-State

High N-terminal pro-brain-type natriuretic peptide levels have been associated with a lower risk of type 2 diabetes mellitus (T2D). However, less is known about other cardiac stress biomarkers in this context. Here we evaluated the association of mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-arginine vasopressin (copeptin), C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM) with incident T2D and changes in glucose metabolism.. We performed a prospective cohort study using data from the population-based KORA F4/FF4 study. 1773 participants (52.3% women) with MR-proANP measurements and 960 (52.7% women) with copeptin, CT-proET-1 and MR-proADM measurements were included. We examined associations of circulating plasma levels of MR-proANP, copeptin, CT-proET-1 and MR-proADM with incident T2D, the combined endpoint of incident prediabetes/T2D and with fasting and 2 h-glucose, fasting insulin, HOMA-IR, HOMA-B and HbA1c at follow-up. Logistic and linear regression models adjusted for age, sex, waist circumference, height, hypertension, total/HDL cholesterol ratio, triglycerides, smoking, physical activity and parental history of diabetes were used to compute effect estimates.. During a median follow-up time of 6.4 years (25th and 75th percentiles: 6.0 and 6.6, respectively), 119 out of the 1773 participants and 72 out of the 960 participants developed T2D. MR-proANP was inversely associated with incident T2D (odds ratio [95% confidence interval]: 0.75 [0.58; 0.96] per 1-SD increase of log MR-proANP). Copeptin was positively associated with incident prediabetes/T2D (1.29 [1.02; 1.63] per 1-SD increase of log copeptin). Elevated levels of CT-proET-1 were associated with increased HOMA-B at follow-up, while elevated MR-proADM levels were associated with increased fasting insulin, HOMA-IR and HOMA-B at follow-up. These associations were independent of previously described diabetes risk factors.. High plasma concentrations of MR-proANP contributed to a lower risk of incident T2D, whereas high plasma concentrations of copeptin were associated with an increased risk of incident prediabetes/T2D. Furthermore, high plasma concentrations of CT-proET-1 and MR-proADM were associated with increased insulin resistance. Our study provides evidence that biomarkers implicated in cardiac stress are associated with incident T2D and changes in glucose metabolism.

Topics: Adrenomedullin; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Female; Germany; Glycopeptides; Heart Diseases; Humans; Incidence; Insulin Resistance; Male; Middle Aged; Peptide Fragments; Prediabetic State; Prognosis; Prospective Studies; Protein Precursors; Risk Assessment; Risk Factors; Time Factors

The exact mechanism of premature atherosclerosis in diabetes is still unclear. Inappropriate activation of the renin-aldosterone-angiotensin system may be an important risk factor for cardiovascular disease. We investigated whether renin and aldosterone are associated with vasoactive peptides midregional-pro atrial natriuretic peptide (MR-proANP) and midregional-pro adrenomedullin (MR-proADM), or with intima media thickness (IMT) as a marker for early atherosclerotic alterations in the general community and in subjects with type 2 diabetes.. In 1261 participants in the KORA F4 study, the associations of renin, aldosterone and aldosterone to renin ratio with MR-proANP, MR-proADM and IMT were assessed using linear regression models stratified for the presence of prediabetes and type 2 diabetes.. After adjustment for confounding factors, an inverse association of MR-proANP with renin (p = 0.002) and aldosterone (p = 0.021) and a direct association of MR-proADM with renin (p < 0.001) and aldosterone (p = 0.019) were seen in nondiabetic individuals. In diabetic subjects, there was no significant correlation of MR-proANP or MR-proADM with renin or aldosterone. Renin and aldosterone were not directly associated with IMT in non-diabetic subjects and the total cohort, whereas aldosterone was associated with IMT in diabetic participants (p = 0.005).. This study shows associations between renin, aldosterone and MR-proANP/MR-proADM plasma levels that are altered in type 2 diabetes. Plasma renin and aldosterone are not independent biomarkers for early atherosclerotic damages of the carotid arteries in the general community.

Topics: Adrenomedullin; Adult; Aged; Aldosterone; Anthropometry; Biomarkers; Carotid Arteries; Carotid Intima-Media Thickness; Cohort Studies; Diabetes Mellitus, Type 2; Disease Progression; Female; Glucose Tolerance Test; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Peptide Fragments; Prediabetic State; Protein Precursors; Renin; Risk Factors

The study of two populations with a recent onset of type 2 diabetes showed that a subset of the patients had higher levels of adrenomedullin (AM) than the rest of the diabetics. In this subset, physiological elevations of AM might have triggered the disease in predisposed individuals. Diabetics showed higher levels of AM than healthy controls. In addition, glycemia was measured in diabetic rats after injection of saline, AM, or antiAM antibody. AM elevated glycemia, whereas the antibody reduced circulating glucose to normal. These results suggest that manipulation of AM levels could represent a new approach in the management of diabetes for the appropriate individuals.

Topics: Adolescent; Adrenomedullin; Adult; Animals; Antibodies; Blood Glucose; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Disease Models, Animal; Female; Humans; Male; Middle Aged; Peptides; Phenotype; Prediabetic State; Pregnancy; Rats; Rats, Inbred SHR