The effects of good glycaemic control on left ventricular and coronary endothelial functions in patients with poorly controlled Type 2 diabetes mellitus.

OBJECTIVE: Diabetics are at risk for developing overt heart failure and subclinical left ventricular (LV) dysfunction. Also, impaired coronary flow reserve (CFR) reflecting coronary microvascular dysfunction is common in diabetics. However, no substantial data regarding the effects of good glycaemic control on subclinical LV dysfunction and CFR are available. CONTEXT: To investigate whether good glycaemic control had favourable effects on subclinical LV dysfunction and CFR. DESIGN: Prospective, open-label, follow-up study. PATIENTS: Diabetics (n = 202) were classified based on baseline HbA1C levels: patients with good (group 1) (<7·0%) and poor glycaemic control (≥7·0%). MEASUREMENTS: All patients underwent echocardiographic examination at baseline evaluation, and it was repeated at months 6 and 12. Based on HbA1C levels obtained at month 6, the patients with poor glycaemic control were divided into two groups: achieved (group 2) and not achieved good glycaemic control (group 3). RESULTS: The groups were comparable with respect to diastolic function parameters including left atrium diameter, mitral E/A, Sm , Em /Am , E/E' and Tei index, and these parameters did not significantly change at follow-up in the groups. At baseline, CFR was slightly higher in group 1 than in group 2 and group 3, but it did not reach statistically significant level. At follow-up, CFR remained unchanged in group 1 (P = 0·58) and group 3 (P = 0·86), but increased in group 2 (P = 0·02: month 6 vs baseline and P = 0·004: month 12 vs baseline). CONCLUSIONS: Diabetics with poor and good glycaemic control were comparable with respect to echocardiographic parameters reflecting subclinical LV dysfunction, and good glycaemic control did not affect these parameters. However, good glycaemic control improved CFR.

Impaired heart rate recovery in patients with endemic fluorosis.

The objective of the present study was to determine the heart rate recovery index (HRRI), a marker of autonomic nervous system function in patients with endemic fluorosis. Forty patients with endemic fluorosis (16 men/24 women) and 40 age-, sex-, and body mass index-matched healthy controls (16 men/24 women) with normal fluoride intake were enrolled in this study. HRRI was calculated by subtracting the heart rate values at the first, second, and third minutes of the recovery phase from the peak heart rate (HRRI 1, HRRI 2, HRRI 3). Urine fluoride levels of fluorosis patients were significantly (P < 0.001) higher than control subjects as expected. HRRI 2 was significantly lower in fluorosis patients than in the controls. The incidence of abnormal HRRI 1 was significantly higher in fluorosis patients than in the controls (P < 0.05). We observed that HRRI, a marker of autonomic nervous system function, is impaired in patients with chronic fluorosis.

Increased plasma neopterin and hs-CRP levels in patients with endemic fluorosis.

Although fluoride induced inflammatory reactions have been shown in animals and in vitro humans, there are few studies about fluoride induced inflammatory reactions in human beings at clinical setting. We aimed to measure the plasma neopterin, a marker of activation of the monocyte/macrophage system, and high sensitivity C-reactive protein (hs-CRP) levels in patients with endemic fluorosis to investigate the possible role of inflammatory processes (monocyte/macrophage activity) in the underlying pathophysiology of fluoride toxicity at clinical level. Plasma neopterin and hs-CRP levels were determined in endemic fluorosis patients and control subjects. Plasma neopterin levels were significantly higher among patients with endemic fluorosis when compared with control group (2.40 ± 0.66 vs. 1.63 ± 0.27 ng/mL respectively; p < 0.001) and plasma hs-CRP levels were also significantly higher among patients with endemic fluorosis when compared with control group (2.41 ± 1.23 vs. 1.93 ± 0.64 mg/L respectively; p < 0.001). Plasma neopterin levels were positively correlated with urine fluoride levels (r = 0.67, p < 0.001) and serum hs-CRP levels were positively correlated with urine fluoride levels (r = 0.36, p < 0.001). We have found that plasma neopterin and hs-CRP levels are increased in patients with endemic fluorosis. We have concluded that inflammation play an important role in the pathophysiology of fluoride toxicity in patients with endemic fluorosis.

Impact of chronic fluorosis on left ventricular diastolic and global functions.

Sixty three patients with endemic fluorosis (36 males/27 females; mean age 33.9+/-8.6years) and 45 age, sex and body mass index (BMI) matched healthy controls (30 males/15 females; mean age 32.7+/-8.8years) were included in this study. Basic echocardiographic measurements, left ventricular diastolic parameters and left ventricular myocardial performance index (MPI) were measured. The left ventricular MPI was calculated as (isovolumic contraction time+isovolumic relaxation time)/aortic ejection time by Doppler. The urine fluoride levels of fluorosis patients were significantly higher than control subjects as expected (1.9+/-0.1mg/l vs 0.4+/-0.1mg/l respectively; P<0.001). Isovolumic relaxation time (IVRT) and deceleration time (DT) were significantly higher in fluorosis patients than in controls (for IVRT 106.9+/-15.6ms vs 96.7+/-12.2ms; P<0.001 and for DT 211.7+/-30.7ms vs 188.0+/-30.0ms; P<0.001, respectively). MPI was significantly higher in fluorosis patients than in controls (0.62+/-0.15ms vs 0.49+/-0.10ms; P<0.001, respectively). We have shown that chronic fluorosis patients had left ventricular diastolic and global dysfunctions.

Aortic elasticity is impaired in patients with endemic fluorosis.

Sixty-three patients with endemic fluorosis (36 males/27 females; mean age 33.9 +/- 8.6 years) and 45 age-, sex-, and body mass index-matched healthy controls (30 males/15 females; mean age 32.7 +/- 8.8 years) were included in this study. Aortic stiffness indices, aortic strain (AS), aortic distensibility (AD), and aortic strain index (ASI) were calculated from the aortic diameters measured by echocardiography and blood pressure obtained by sphygmomanometry. The urine fluoride levels of fluorosis patients were significantly higher than control subjects as expected (1.9 +/- 0.1 mg/l vs. 0.4 +/- 0.1 mg/l, respectively; P < 0.001). AS and AD were significantly lower in fluorosis patients than in the controls (for AS 5.3 +/- 3.6 vs. 8.0 +/- 3.4%; P < 0.001 and for AD 0.2 +/- 0.1 vs. 0.3 +/- 0.1 cm(2) dyn(-1) 10(-3); P < 0.001, respectively). In contrast, significantly higher ASI was observed in fluorosis patients than in the controls (3.4 +/- 0.6 vs. 3.0 +/- 0.4; P < 0.001, respectively). The results of our study demonstrate that elastic properties of ascending aorta are impaired in patients with endemic fluorosis.