[Show abstract][Hide abstract] ABSTRACT: GH reduces insulin sensitivity (IS), whereas IGF-I increases it. IGF-I seems to be critical for the development of the β-cells, and impaired IS has been reported in GH deficiency (GHD).
The aim of the study was to assess IS and β-cell function in adult patients with untreated isolated GHD (IGHD) due to a homozygous mutation in the GHRH receptor gene.
We conducted a cross-sectional study in 24 GH-naive adult IGHD subjects and 25 controls.
We performed an oral glucose tolerance test with glucose and insulin measurements at 0, 30, 60, 90, 120, and 180 min.
IS was assessed by homeostasis model assessment index of insulin resistance (IR), quantitative IS check index, oral glucose IS in 2 h (OGIS2) and 3 h (OGIS3). β-Cell function was assayed by homeostasis model assessment index-β, insulinogenic index, and area under the curve of insulin-glucose ratio.
During the oral glucose tolerance test, glucose levels were higher in IGHD subjects (P<0.0001), whereas insulin response presented a trend toward reduction (P=0.08). The number of individuals with impaired glucose tolerance was higher in the IGHD group (P=0.001), whereas the frequency of diabetes was similar in the two groups. Homeostasis model assessment index of IR was lower (P=0.04), and quantitative IS check index and OGIS2 showed a nonsignificant trend toward elevation (P=0.066 and P=0.09, respectively) in IGHD. OGIS3 showed no difference between the groups. Homeostasis model assessment index-β, insulinogenic index, and ratio of the areas of the insulin and glucose curves were reduced in the IGDH group (P=0.015, P<0.0001, and P=0.02, respectively).
Adult subjects with lifetime congenital untreated IGHD present reduced β-cell function, no evidence of IR, and higher frequency of impaired glucose tolerance.
The Journal of Clinical Endocrinology and Metabolism 12/2011; 97(3):1013-9. DOI:10.1210/jc.2011-2590 · 6.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although chronotropic incompetence (CI) represents an independent predictor of mortality and incidence of coronary artery disease, its pathophysiological mechanisms remain unknown. The purpose of this investigation was to evaluate wall motion abnormalities of the left ventricle and location of coronary arterial lesions in patients with and without CI.
After exclusion of confounding factors, 610 patients (mean age of 58.4 +/- 11 years; 275 men) with ischaemia who underwent exercise echocardiography were studied. Based on heart rate (HR) reached in treadmill testing, patients were divided into two groups: Chl (97 patients who did not reach 85% of maximum HR recommended for age) and ChC (513 patients who achieved 85% of the maximum age-predicted HR).
There was a higher frequency of dyspnoea (5.2% vs. 0.6%, P = 0.003), systemic hypertension (69.1% vs. 57.3%, P = 0.031) and obesity (38.1% vs. 22.6%, P = 0.001), and a lower tolerance to effort (dyspnoea as limitation of physical effort: 36.1% vs. 8.0%, P < 0.0001; duration of treadmill test: 4.4 +/- 2.2 vs. 7.2 +/- 2.8, P < 0.0001; METs: 6.0 +/- 2.6 vs. 8.4 +/- 2.9, P = 0.002) in Chl compared to ChC. The wall motion score index (WMSI) was higher in Chl than in ChC, both at rest (1.15 +/- 0.29 vs. 1.07 +/- 0.19, P = 0.011) and after exercise (1.24 +/- 0.29 vs. 1.15 +/- 0.19, P = 0.002). Systolic function, which was evaluated in peak exercise through WMSI, was significantly more altered in the Chl group. The presence of severe injuries in right coronary was independently associated with CI (adjusted OR = 3.57, CI 95%: 1.86-6.87).
Chronotropic incompetence is associated with ventricular dysfunction in peak exercise and critical right coronary artery lesions.
[Show abstract][Hide abstract] ABSTRACT: Coronary artery disease (CAD) is the leading cause of death in diabetic patients. Although exercise echocardiography (EE) is established as a useful method for diagnosis and stratification of risk for CAD in the general population, there are few studies on its value as a prognostic tool in diabetic patients. The purpose of this investigation was to evaluate the value of EE in predicting cardiac events in diabetics.
193 diabetic patients, 97 males, 59.8 +/- 9.3 yrs (mean +/- SD) were submitted to EE between 2001 and 2006 and followed from 7 to 65 months with median of 29 months by phone calls and personal interviews with patients and their primary physician, and reviewing medical records and death certificates. The end points were cardiac events, defined as non-fatal myocardial infarction, late myocardial revascularization and cardiac death. Sudden death without another explanation was considered cardiac death. Survival free of end points was estimated by the Kaplan-Meier method.
Twenty-six cardiac events were registered in 24 individuals during the follow-up. The rates of cardiac events were 20.6 and 7% in patients with positive and negative EE, respectively (p < 0.001). Predictors of cardiac events included sedentary lifestyle, with RR of 2.57 95%CI [1.09 to 6.02] (P = 0.03) and positive EE, with RR 3.63, 95%CI [1.44 to 9.16] (P = 0.01). Patients with positive EE presented higher rates of cardiac events at 12 months (6.8% vs. 2.2%), p = 0.004.
EE is a useful method to predict cardiac events in diabetic patients with suspected or known CAD.
[Show abstract][Hide abstract] ABSTRACT: In the last twenty years, recombinant human Growth hormone (hrGH) has been available for the treatment of Growth Hormone Deficiency (GHD) in children and more recently in adults. However, the necessity of daily injections compromises the patient's compliance. Attempts to improve this compliance includes the use of pens and needle free devices, once the infusion pumps, not always physiologic, are of restricted use. When growth is the purpose of treatment, daily subcutaneous hrGH is still the most indicated. Nevertheless the expansion of GH replacement to new uses and especially in adults will need new preparations. Nowadays, the oral secretagogues have not proved efficacy to be used in clinical practice and the slow- release preparations of GH and GH releasing hormone that could improve the patient's compliance will need to be studied considering long term efficacy and safety.
Arquivos brasileiros de endocrinologia e metabologia 08/2008; 52(5):917-24. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: GH deficiency (GHD) in adults is associated with increased abdominal adiposity and systolic blood pressure, total and low-density lipoprotein cholesterol, and C-reactive protein.
We have studied the effects of 6-month GH replacement therapy in 20 adult members of a large Brazilian kindred with lifelong severe and isolated GHD due to a homozygous mutation in GHRH receptor gene (46 +/- 14.5 yr; 122 +/- 7.7 cm; 36.7 +/- 5.4 kg; 10 men). Subjects were studied at baseline, after 6-month bimonthly depot GH injections (Nutropin Depot; Genentech, Inc., South San Francisco, CA) [post GH (pGH)], and after 6- and 12-month washout.
Despite modest trough serum IGF-I increase, GH replacement therapy caused a decrease in skinfolds and in waist-hip ratio, with a rebound increase at 12 months. Total and low-density lipoprotein cholesterol were reduced pGH and returned to baseline at 6 months. High-density lipoprotein cholesterol increased pGH, but at 12 months was lower than baseline. A progressive increase in left ventricular mass index, posterior wall, and septum thickness occurred from pGH to 12 months, and of carotid intima-media thickness, from 6 to 12 months. Individuals were 6, 16, and 52 times more likely to have an atherosclerotic carotid plaque at pGH, 6 and 12 months, respectively, when compared with baseline.
In patients with lifetime isolated GHD, 6-month treatment with GH has reversible beneficial effects on body composition and metabolic profile, but it causes a progressive increase in intima-media thickness and in the number of atherosclerotic carotid plaques.
[Show abstract][Hide abstract] ABSTRACT: Exercise echocardiography (EE) is an established method to diagnose coronary artery disease (CAD). Chronotropic incompetence (CI) during the EE may be a marker of myocardial ischemia. The purpose of this investigation was to evaluate the additive value of CI during EE in CAD diagnosis.
Between 2000 and 2006, 4042 patients (1900 men with a mean age of 56 +/- 11 years) were evaluated by EE. Based on the heart rate (HR) reached during the exercise test, the subjects were divided into two groups: G1 group - 490 patients who failed to achieve 85% of the maximal age-predicted HR, and G2 group - 3552 patients who were able to achieve 85% of the maximal age-predicted HR. Clinical characteristics, left ventricular wall motion abnormalities - wall motion score index (WMSI) - and coronary angiography (CA) were the parameters compared between the two groups.
The left ventricular wall motion abnormalities were more frequent in G1 group than in G2 group (54% versus 26%; P < 0.00001). WMSI was higher in G1 group than in G2 group, both at rest (1.06 +/- 0.17 versus 1.02 +/- 0.09; P < 0.0001) and after exercise (1.12 +/- 0.23 versus 1.04 +/- 0.21; P < 0.0001). In G1 group, 82% of the patients with positive EE for myocardial ischemia presented obstructive coronary, compared to 71% (P = 0.03) in G2 group.
CI is associated with a higher frequency of myocardial ischemia during EE, reinforcing the concept that CI is a marker of the severity of myocardial ischemia.