Impact of glucose intolerance and insulin resistance on cardiac structure and function: sex-related differences in the Framingham Heart Study

Framingham Heart Study, Burlington, Mass, USA.
Circulation (Impact Factor: 14.43). 01/2003; 107(3):448-54.
Source: PubMed


Although insulin resistance has been implicated in the pathogenesis of left ventricular (LV) hypertrophy, previous studies have yielded inconsistent results and are limited by referral bias.
We examined the relations between echocardiographic LV measurements and glucose tolerance status in 2623 Framingham Study subjects (1514 women, mean age 53 years) free of myocardial infarction and heart failure. We also evaluated the relations of insulin resistance (homeostasis model, HOMA-IR) and LV and left atrial (LA) measures within the normal and abnormal glucose tolerance categories (the latter included impaired glucose tolerance, impaired fasting glucose, and newly diagnosed diabetes). LV mass (adjusted for age, height, heart rate, and systolic blood pressure) increased across categories of worsening glucose tolerance; the trend was more striking in women (P<0.001) compared with men (P=0.054). In subjects with normal (n=2022) and abnormal glucose tolerance (n=327), covariate-adjusted LV mass and LV wall thickness increased across HOMA-IR quartiles in women (P<0.001) but not men. In contrast, covariate-adjusted LA size increased with worsening glucose tolerance and across HOMA-IR quartiles in the normal and abnormal glucose tolerance groups in both sexes. Adjustment for body mass index considerably attenuated the relations of LV/LA measures and HOMA-IR, rendering them statistically nonsignificant in the normal glucose tolerance group.
In our large community-based sample, LV mass and wall thickness increased with worsening glucose intolerance, an effect that was more striking in women compared with men. Insulin resistance was associated with increased LV mass in women alone, but this relation was largely accounted for by obesity.

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Available from: Helen Parise, Jan 21, 2014
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    • "LVMI and possibly also RWT are significantly greater among patients with DM than those without, and the case may be the same for subjects with impaired glucose tolerance (IGT) [14] [15] [16] [17] [18] [19] [20]. However, only few studies have investigated the association between DM and LVM after adjusting for body size and other traditional risk factors [14] [15] [16] [17] [18] [19], and whether a graded association between fasting plasma glucose (FPG) category and LVM and geometry exists, has not been clearly established. Given these knowledge gaps, a comprehensive evaluation of LV size and geometry and their relation to fasting glucometabolic status is justified and may reveal putative mechanisms for the development of LVH in subjects with impaired glucose metabolism. "
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    ABSTRACT: Background/objectives: To examine whether higher fasting plasma glucose (FPG) levels were independently associated with left ventricular (LV) mass and/or geometry in elderly, otherwise healthy subjects. Methods: We tested cross-sectional associations between echocardiographically determined LV mass/geometric patterns, cardiovascular risk factors, and FPG categorized as normal fasting glucose (NFG), impaired fasting glucose (IFG), and untreated diabetes mellitus (DM), in 486 men and 207 women aged 56–79 years without overt cardiovascular disease, who received no cardiovascular, anti-diabetic, or lipid-lowering drugs and had a preserved LV ejection fraction >50%. Results: Unadjusted mean LV mass index (LVMI) was significantly greater among subjects with DM than those without (90 +/− 26 g/m2 vs. 85 +/− 20 g/m2, p = 0.01), as were both relative wall thickness (RWT) (0.43 +/− 0.09 vs. 0.40 +/− 0.08, p = 0.01) and prevalence of concentric LV hypertrophy (LVH) (11% vs. 6%, p = 0.03). However, only RWT remained significantly associated with the presence of DM after multivariable adjustment (p = 0.04). Interaction analyses revealed that greater LVMI/LVH was predominantly associated with higher levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) among subjects with IFG orDM, but notNFG. Conclusions: Subjects with untreated DMhad higher values of LVMI and a greater prevalence of concentric LVH, but the associations were not independent of other risk factors. NT-proBNP was primarily associated with greater LV size in subjects with IFG or DM.
    IJC Metabolic and Endocrine 12/2015; 9:39-47. DOI:10.1016/j.ijcme.2015.10.005
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    • "The Latin-American Diabetes Association (ALAD) Clinical Guides [12] [13] as well as the Clinical Guide from Chilean Health Ministry suggested the diagnosis of IFG when the fasting plasma glucose is between 100 and 125 mg/dL [14]. Beyond the differences existing in order to establish the normal limit for fasting plasma glucose, the evidences coincide that glucose levels in the stage of prediabetic keep a direct relation with the risk of developing diabetes in the future, and this also constitutes an independent risk factor for cardiovascular diseases (CVD) [15] [16]. Both conditions, T2DM and CVD, are related with other factors such as dyslipidemia , arterial hypertension (HTA), abdominal obesity, sedentary, oxidative stress, metabolic syndrome (MS), and family data [17] [18]. "
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    ABSTRACT: Aim: To study the evolution of impaired fasting glucose (IFG), considering glucose and HbA1c levels and risk factors associated, in a period of 6 years. Methods: We studied 94 subjects with impaired fasting glucose (IFG) that were diagnosed in 2005 and followed up to 2012. Glucose and HbA1c levels were determined. A descriptive analysis of contingence charts was performed in order to study the evolution in the development of type-2 diabetes mellitus (T2DM). Results: Twenty-eight of ninety-four subjects became T2DM; 51/94 remained with IFG; and 20/94 presented normal fasting glucose. From the 28 diabetic subjects, 9 had already developed diabetes and were under treatment with oral hypoglycemic agents; 5 were diagnosed with plasma glucose < 126 mg/dL, but with HbA1c over 6.5%. In those who developed diabetes, 15/28 had a family history of T2DM in first relative degree. Also, diabetic subjects had a BMI significantly higher than nodiabetics (t test: P < 0.01). The individuals that in 2005 had the highest BMI are those who currently have diabetes. Conclusion: The IFG constitutes a condition of high risk of developing T2DM in a few years, especially over 110 mg/dL and in obesity patients.
    Journal of Diabetes Research 08/2014; 2014(9541):710370. DOI:10.1155/2014/710370 · 2.16 Impact Factor
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    • "Cardiac imaging in db/db mice showed diastolic insufficiency and increased systolic function. These alterations are similar to findings from patients with insulin resistance and early-stage diabetes that show diastolic dysfunction, but no signs of systolic impairment or structural changes [44,45]. The smaller weight of the db/db hearts is in part explained bý the shorter LV parasternal length. "
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    ABSTRACT: Background The aim of this study was to probe cardiac complications, including heart-rate control, in a mouse model of type-2 diabetes. Heart-rate development in diabetic patients is not straight forward: In general, patients with diabetes have faster heart rates compared to non-diabetic individuals, yet diabetic patients are frequently found among patients treated for slow heart rates. Hence, we hypothesized that sinoatrial node (SAN) dysfunction could contribute to our understanding the mechanism behind this conundrum and the consequences thereof.Methods Cardiac hemodynamic and electrophysiological characteristics were investigated in diabetic db/db and control db/+mice.ResultsWe found improved contractile function and impaired filling dynamics of the heart in db/db mice, relative to db/+controls. Electrophysiologically, we observed comparable heart rates in the two mouse groups, but SAN recovery time was prolonged in diabetic mice. Adrenoreceptor stimulation increased heart rate in all mice and elicited cardiac arrhythmias in db/db mice only. The arrhythmias emanated from the SAN and were characterized by large RR fluctuations. Moreover, nerve density was reduced in the SAN region.Conclusions Enhanced systolic function and reduced diastolic function indicates early ventricular remodeling in obese and diabetic mice. They have SAN dysfunction, and adrenoreceptor stimulation triggers cardiac arrhythmia originating in the SAN. Thus, dysfunction of the intrinsic cardiac pacemaker and remodeling of the autonomic nervous system may conspire to increase cardiac mortality in diabetic patients.
    Cardiovascular Diabetology 08/2014; 13(1):122. DOI:10.1186/s12933-014-0122-y · 4.02 Impact Factor
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