Presentations in this session provided insights regarding the effects of insulin resistance in obese children and adolescents, the role of adrenergic activity in the development of obesity, the effects of sibutramine on blood pressure, and the role of insulin resistance and adrenergic activity in the development of organ damage.
A study from Spain in 87 overweight (BMI 85th-97th percentile) and obese (threshold BMI “z” score >2) children (6-18 years, mean age 10.9 yrs) showed that in nocturnal systolic blood pressure (SBP) and nocturnal heart rate were significantly higher in the highest tertile of HOMA index, after adjustment for age, sex, and height. Daytime SBP and heart rate were not different between the groups in this study presented by Prof. E. Lurbe, Valencia, Spain. A significant relationship between nocturnal SBP and fasting insulin and HOMA index, when adjusted for age, and sex was found. The BMI z score was more closely related to blood pressure, and waist circumference was more closely related to insulin resistance. Both parameters were mainly associated with increase in nighttime, but not daytime, blood pressure. A clear effect of insulin resistance on nighttime SBP was seen across the BMI range. The data suggest that these findings may be predictive of hypertension-related hypertension and may contribute to an increased cardiovascular risk.
Reduced adrenergic reactivity to mental stress is a strong predictor of future obesity, according to results of the first-long term study of the relation between the sympathoadrenal system and obesity. Prof. A. Flaa, Oslo, Norway, stated that the sympathetic noradrenergic and adrenomedullary activity may operate in a reciprocal manner in obesity development.
The study assessed arterial epinephrine (E) and norepinephrine (NE) at rest and in response to a mental stress test and cold pressor test in relation to weight at study entry and at the end of the 18-year follow-up in 80 healthy men (at study entry mean age 19.3 years, BMI 22.3Kg/m2, waist circumference 82.7 cm).
Overweight men (BMI >25 kg/m2) at follow-up were found to have at study entry a higher BMI and waist circumference and significantly lower E and NE responses. Men with central obesity (waist circumference >/=94 cm) had at study entry a higher BMI and waist circumference and significantly lower E response at rest and lower NE response on mental stress test.
Adrenaline response to mental stress was a consistent negative predictor of future waist circumference, BMI, and triceps skinfold thickness. Noradrenaline response to mental stress was a positive predictor of waist circumference and near significant predictor of BMI and triceps skinfold thickness in multiple regression analysis.
A retrospective analysis of nine randomized trials with sibutramine in obese persons showed that despite a greater reduction in weight and waist circumference, this was not associated with a greater reduction in blood pressure (BP). The greatest BP reduction was seen in persons with a higher baseline level of BP. In the persons taking sibutramine who had < 5% weight loss and/or who had the lowest baseline BP, a slight increase in BP was seen. Prof. A. Sharma of Hamilton, Canada presented the results.
This analysis included persons who were obese (BMI >/=30 or BMI >27 + comorbidities) who had normal BP or controlled hypertension and who were treated with lifestyle changes and sibutramine 10-15 mg (n=1212) or placebo (n-915). Patients were stratified by baseline SBP (</=115, >115-140, >140 mmHg).
In the hypertensives, the mean BP reduction was -6.2/-1.0 mmHg in the sibutramine group and -6.9/-2.3 mm Hg in the control group. Other key findings are shown in the Table.
The results of the 6-week single-blind, lead-in period of the SCOUT study with sibutramine, presented by Prof.A. Maggioni of Florence, Italy, suggest that the drug has a central clonidine-like effect on BP. In hypertensives, no relation between weight loss and BP reduction was found, while in the BP-controlled/normotensives, a weight loss ≥ 5% was associated with a reduction in SBP.
The study of 10,972 high-risk overweight and obese persons (mean age 63 years) is an ongoing study evaluating the effects of sibutramine 10 mg plus lifestyle changes for weight management. No changes were made to antihypertensive therapy. Patients were identified as “BP-controlled” or normotensive (<140/90 mmHg or 130/80 mmHg in diabetics) or hypertensive (75%). Changes in BP were stratified by categories of weight change and the number of concomitant medications during the lead-in period.
In 11% of the hypertensives, no weight change occurred and the median BP reduction was 2.5/0.5 mmHg, while in 11% of the BP-controlled/normotensives with no weight change, the median BP change was 3.0-5.0/2.5-4.0 mmHg. In the 12% of the BP-controlled/normotensives with a weight loss >/=5%, the median BP change was -2.5/0.0 mmHg with no concomitant medications, -2.5/1.0 mmHg with 1 concomitant medication, and -1.0/+0.5 mmHg with >/=2 concomitant medications.
An Italian study of 32 men (mean age 42 years) with abdominal obesity and 10 age-matched healthy men provided the first data to implicate insulin resistance and adrenergic activation in the development of left ventricular hypertrophy (LVH) secondary to obesity.
Mean arterial pressure (MAP), heart rate (HR), MSNA, and HOMA index (HI) were assessed in the hypertensives and normotensives with or without LVH. MSNA and HI, measures of sympathetic and metabolic activity, were significantly higher in the obese men compared to the controls. Notably, MSNA and HI were significantly greater in the obese men with LVH compared to those without LVH (57.5 vs 47.2 bs/100 hb; 4.9 vs 3.3 a.u., respectively), and in the obese with hypertension the values were also significant (715 vs 60.9 bs/100 hb; 5.1 vs 3.9 a.u., respectively).
In the obese men, baroflex control of MSNA and heart rate was significantly attenuated in the presence of left ventricular hypertrophy (LVH).