Cardiovascular characteristics in subjects with increasing levels of abnormal glucose regulation: the Strong Heart Study.

OBJECTIVE: To evaluate whether impaired fasting glucose (IFG) or the combination of IFG and impaired glucose tolerance (IGT) is associated with progressive abnormalities of cardiac geometry and function. RESEARCH DESIGN AND METHODS: We studied 562 nondiabetic (311 women), nonhypertensive participants of the second Strong Heart Study exam, without prevalent cardiovascular (CV) disease and with estimated glomerular filtration rate ≥60 mL/min/1.73 m(2) (age 46-65 years, 198 with isolated IFG [35%], and 132 with combined IFG and IGT [23%]). Anthropometric parameters, insulin resistance, fibrinogen, C-reactive protein (CRP), lipid profile, blood pressure (BP), and echocardiographic parameters were compared with 232 participants with normal glucose tolerance (NGT). RESULTS: BMI, prevalence of central obesity, homeostatic model assessment index of insulin resistance, plasma triglycerides, fibrinogen, and CRP increased progressively across categories of glucose intolerance (P < 0.0001), with the IFG+IGT group having higher values than those with isolated IFG (0.05 < P < 0.0001). Compared with NGT, both IFG and IFG+IGT exhibited greater left ventricular (LV) mass (P < 0.0001) and lower Doppler early peak rapid filling velocity to peak atrial filling velocity ratio (P < 0.005), without differences in LV systolic function. The odds of LV hypertrophy (LV mass index >46.7 in women or >49.2 g/m(2.7) in men) was 3.5 in IFG participants (95% CI 0.68-17.76; P = NS) and 9.76 (2.03-46.79; P = 0.004) in IFG+IGT, compared with NGT, after adjustment for age, sex, heart rate, systolic BP, and waist circumference (WC). In the overall sample, LV mass index was associated with WC (P = 0.033), CRP (P = 0.027), and 2-h oral glucose tolerance test (P = 0.001) independently of confounders. CONCLUSIONS: Cardiometabolic profile and markers of inflammation are more severely altered in men and women with both IFG and IGT compared with those with IFG alone. These individuals, in the absence of hypertension, have a 10-fold greater probability of preclinical CV disease (LV hypertrophy).

Uncomplicated type 1 diabetes and preclinical left ventricular myocardial dysfunction: insights from echocardiography and exercise cardiac performance evaluation.

OBJECTIVES: Left ventricular (LV) diastolic dysfunction is considered the earliest manifestation of diabetic cardiomyopathy. Whether LV abnormalities identified at rest by echocardiography predict peak exercise LV performance in uncomplicated type 1 diabetes mellitus (DM1) is largely unknown. RESEARCH DESIGN AND METHODS: We evaluated LV size, mass, and functions and peak exercise LV performance in 25 subjects with uncomplicated DM1 (median disease duration 13.5 years, 1-30 years) and in 56 non-DM subjects (24 hypertensive (HT) and 32 normotensive (NT)). Overt coronary heart disease, significant microangiopathy and central autonomic neuropathy were minimized by exclusion criteria. Peak exercise LV stroke index (SVi), cardiac index (COi), LV ejection fraction (EF), LV end-diastolic and end-systolic volumes were assessed noninvasively. No subject was on cardiovascular medications at the time of evaluation. RESULTS: In our study, DM1 did not show LV hypertrophy or impaired LV systolic function at rest. Prevalence of diastolic dysfunction was 8% among DM1, 18% among NT and 50% among HT. Pre-exercise heart rate, SVi, COi, and peak exercise blood pressure (BP) and heart rate were comparable among the three groups, but peak exercise LV EF, SVi and COi were lower in DM1 than in HT and NT independent to covariates (p<0.05). In separate analyses, DM1 predicted lower peak exercise SVi (B=-6.2) and COi (B=-1.6, both p<0.05) independently. Within DM1, glycated haemoglobin (HbA1c) and disease duration did not predict peak exercise LV systolic function. CONCLUSIONS: Our study suggests that uncomplicated DM1 may be associated with subnormal LV contractility reserve, which might not be predicted by LV dysfunction evaluated at rest.

Left ventricular chamber and myocardial systolic function reserve in patients with type 1 diabetes mellitus: insight from traditional and Doppler tissue imaging echocardiography.

OBJECTIVE: We sought to evaluate in patients with type 1 diabetes mellitus (DM1): (1) whether myocardial afterload correlates with left ventricular (LV) circumferential and longitudinal systolic function at rest and during low-dose dobutamine (LDD) infusion, and whether longitudinal and circumferential LV systolic function reserves are correlated; and (2) to explore relations between LV systolic mechanics and LV chamber output reserves. METHODS: A total of 20 patients with DM1 underwent echocardiography to assess LV systolic function at rest and at peak LDD (7.5 microg/kg/min). At rest, echocardiographic data of patients with DM1 were compared with those from 24 healthy control subjects. LV afterload was estimated by computing circumferential end-systolic stress (ESS). LV chamber systolic function was assessed by computing ejection fraction and ESS/end-systolic volume index; LV circumferential myocardial contractility was explored by computing midwall fractional shortening (MWS) and ESS-corrected MWS. Longitudinal LV systolic function was assessed using color Doppler tissue (DTI) to assess peak systolic velocities and maximal displacement of the lateral and medial mitral annulus in apical 4-chamber view; regional deformation analyses were computed at the midportion of the posterior interventricular septum (peak strain and peak strain rate); strain/ESS was assessed as an alternative indicator of longitudinal myocardial contractility. LV chamber output was assessed by computing stroke index. RESULTS: DM1 and control groups did not differ in terms of sex distribution, mean age, blood pressure, LV mass index and geometry, and at-rest parameters of LV systolic function (all P > .1), whereas body mass index was higher and systolic lateral mitral annulus velocity was lower in the DM1 than control group (both P < .01). At rest, in both groups, higher ESS correlated with lower ejection fraction and lower MWS; ESS did not show significant correlation with longitudinal systolic function parameters. At peak LDD in DM1, heart rate changed minimally; ESS decreased significantly (P < .01); circumferential and longitudinal LV systolic functions increased significantly but did not show intercorrelation; higher ESS correlated with lower ejection fraction; longitudinal LV systolic function parameters did not show correlation with ESS. In a multivariate analysis, percent increase in stroke index correlated with percent change of MWS (beta = 0.74, P < .01), and to a lesser extent with the percent increase of systolic lateral mitral annulus velocity (beta = 0.47, P = .04), independent to age, sex, percent change of ESS, and heart rate. CONCLUSIONS: LV longitudinal systolic function (DTI) parameters did not fall into the paradigm of the stress-shortening relationship used to describe LV contractility. However, both LV circumferential contractility and longitudinal systolic function reserves correlated with stroke index reserve during LDD.