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Neuroadrenergic dysfunction along the diabetes continuum: a comparative study in obese metabolic syndrome subjects.

ABSTRACT: Neuroadrenergic function in type 2 diabetic (T2D) patients without neuropathy is poorly characterized. We therefore compared sympathetic nervous system activity at rest and during an oral glucose tolerance test in obese metabolic syndrome (MetS) subjects classified as glucose intolerant (impaired glucose tolerance [IGT]; n = 17) or treatment-naive T2D (n = 17). Untreated subjects, matched for age (mean 59 ± 1 year), sex, BMI (32.4 ± 0.6 kg/m(2)), and family history of diabetes were studied. We measured resting muscle sympathetic nerve activity (MSNA) by microneurography, whole-body norepinephrine kinetics by isotope dilution, insulin sensitivity by euglycemic-hyperinsulinemic clamp (steady-state glucose utilization adjusted for fat-free mass and steady-state insulin concentration [M/I]), and MetS components. T2D subjects had higher resting MSNA burst incidence (67 ± 4 versus 55 ± 3 bursts per 100 heartbeats; P = 0.05) and arterial norepinephrine levels (264 ± 33 versus 167 ± 16 pg/mL; P = 0.02), lower plasma norepinephrine clearance (by 17%; P = 0.03), and reduced neuronal reuptake compared with IGT subjects (by 46%; P = 0.04). Moreover, norepinephrine spillover responses to glucose ingestion were blunted in T2D subjects. The M/I value independently predicted whole-body norepinephrine spillover (r = -0.47; P = 0.008), whereas fasting insulin level related to neuronal norepinephrine reuptake (r = -0.35, P = 0.047). These findings demonstrate that progression to T2D is associated with increased central sympathetic drive, blunted sympathetic responsiveness, and altered norepinephrine disposition.

SUBMITTER: Straznicky NE

PROVIDER: S-EPMC3447913 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Neuroadrenergic dysfunction along the diabetes continuum: a comparative study in obese metabolic syndrome subjects.

Straznicky Nora E NE Grima Mariee T MT Sari Carolina I CI Eikelis Nina N Lambert Elisabeth A EA Nestel Paul J PJ Esler Murray D MD Dixon John B JB Chopra Reena R Tilbrook Alan J AJ Schlaich Markus P MP Lambert Gavin W GW

Diabetes 20120604 10

Neuroadrenergic function in type 2 diabetic (T2D) patients without neuropathy is poorly characterized. We therefore compared sympathetic nervous system activity at rest and during an oral glucose tolerance test in obese metabolic syndrome (MetS) subjects classified as glucose intolerant (impaired glucose tolerance [IGT]; n = 17) or treatment-naive T2D (n = 17). Untreated subjects, matched for age (mean 59 ± 1 year), sex, BMI (32.4 ± 0.6 kg/m(2)), and family history of diabetes were studied. We m ...[more]

PMID: 22664956

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Project description:IntroductionErectile dysfunction (ED) is more common in men with type 2 diabetes mellitus (T2DM), obesity, and/or the metabolic syndrome (MetS).AimThe aim of this study is to investigate the associations among proxy measures of diabetic severity and the presence of MetS with ED in a nationally representative U.S. data sample.MethodsWe performed a cross-sectional analysis of adult participants in the 2001-2004 National Health and Nutrition Examination Survey.Main outcome measuresED was ascertained by self-report. T2DM severity was defined by calculated measures of glycemic control and insulin resistance (IR). IR was estimated using fasting plasma insulin (FPI) levels and the homeostasis model assessment of IR (HOMA-IR) definition. We classified glycemic control using hemoglobin-A1c (HbA1c) and fasting plasma glucose (FPG) levels. MetS was defined by the American Heart Association and National Heart, Lung, and Blood Institute criteria. Logistic regression models, adjusted for sociodemographics, risk factors, and comorbidities, were fitted for each measure of T2DM severity, MetS, and the presence of ED.ResultsProxy measures of glycemic control and IR were associated with ED. Participants with FPG between 100-126 mg/dL (5.6-7 mmol/L) and ? 126 mg/dL (>7 mmol/L) had higher odds of ED, odds ratio (OR) 1.22 (confidence interval or CI, 0.83-1.80), and OR 2.68 (CI, 1.48-4.86), respectively. Participants with HbA1c 5.7-6.4% (38.8-46.4 mmol/mol) and ? 6.5% (47.5 mmol/mol) had higher odds of ED (OR 1.73 [CI, 1.08-2.76] and 3.70 [CI, 2.19-6.27], respectively). When FPI and HOMA-IR were evaluated by tertiles, there was a graded relation among participants in the top tertile. In multivariable models, a strong association remained between HbA1c and ED (OR 3.19 [CI,1.13-9.01]). MetS was associated with >2.5-fold increased odds of self reported ED (OR 2.55 [CI, 1.85-3.52]).ConclusionsPoor glycemic control, impaired insulin sensitivity, and the MetS are associated with a heightened risk of ED.

Dataset Information

Neuroadrenergic dysfunction along the diabetes continuum: a comparative study in obese metabolic syndrome subjects.

Publications

Neuroadrenergic dysfunction along the diabetes continuum: a comparative study in obese metabolic syndrome subjects.

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