Health-related quality of life in a randomised placebo-controlled trial of sibutramine in obese patients with type II diabetes.

OBJECTIVE: We evaluated the effects of 12-month treatment with sibutramine 15 mg daily compared with placebo on health-related quality of life (HRQL) in obese type II diabetes patients. We examined the associations between the changes in HRQL and in weight, glycaemic control, and haemodynamic variables. We also explored the predictive value of HRQL and its changes early during treatment. DESIGN: A randomised clinical trial. The subjects were enrolled in a 2-week single-blind run-in period with a modestly hypocaloric diet (700 kcal daily deficit) and then randomised to receive either sibutramine 15 mg (n=114, 60% female) or placebo (n=122, 58% female) once daily with the hypocaloric diet for 12 months. SUBJECTS: Obese (mean BMI 36 kg/m(2) and age 54 y) type II diabetes patients untreated with antidiabetic medications. MEASUREMENTS: The main outcome measures included body weight and HRQL (the RAND 36-Item Health Survey 1.0). RESULTS: The mean weight loss was greater in the sibutramine group (-7.1 kg) than in the placebo group (-2.6 kg, P<0.001). The baseline HRQL was relatively high. There were no significant differences between the treatment groups in glycaemic control or in any of the RAND-36 scales during the study. The scores on physical functioning (PF) and health change (HC) since last year improved in both groups and this improvement was related to weight loss. When HRQL changes were examined in categories of weight loss, the scores on PF and HC increased with >/=5% weight loss, but the scores on vitality (V) and general health (GH) increased only after >/=15% weight loss. Decrease in HbA1c was associated with increases in the scores of PF, GH, V, mental health, and HC. In the sibutramine group, the increase in diastolic blood pressure was associated with the decrease in the scores of PF, physical role functioning, emotional role functioning (ERF), social functioning (SF), and bodily pain. High baseline scores on ERF and SF, and low scores on V predicted weight loss at 12 months. Also, increasing scores on PF and V during the first 3 months predicted weight loss at 12 months. The sum of four dichotomised HRQL variables (baseline ERF >/=75=1 and <75=0; baseline SF>/=80=1 and <80=0; 3-month change in PF>0=1 and 0=1 and /=5% weight loss, but >/=15% weight loss was needed to achieve a cluster of HRQL improvements. The decrease in HbA1c was associated with many HRQL benefits. Poor baseline HRQL and the improvement observed in the first months of treatment may prove to be useful in predicting success in long-term weight loss.

The effect of orlistat on the fatty acid composition of serum lipid fractions in obese subjects.

OBJECTIVE: To determine whether there are any changes in the fatty acid composition of serum triglycerides, cholesterol esters, and phospholipids induced by administration of orlistat three times a day compared with placebo as combined with a low-fat hypocaloric diet. METHODS: After 4 weeks of placebo administration, 75 obese subjects were randomized to receive either one capsule (120 mg) of orlistat or placebo three times a day with meals for 1 year in conjunction with a nutritionally balanced hypocaloric diet. Food records were kept to estimate the nutrient intake. The fatty acid composition of serum lipids were analyzed with gas chromatograph. The molar percentage proportions of fatty acids in serum lipid fractions were calculated. RESULTS: Compared with placebo, there was a significant decrease in the proportion of linoleic acid in triglycerides, cholesterol esters, and phospholipids in the orlistat group, even after the effect of the decrease in the linoleic acid dietary intake (percent of energy), weight change, and gender were taken into account. However, the use of orlistat explained only 9% to 13% of the decrease in the proportion of linoleic acid in serum cholesterol esters, triglycerides, and phospholipids. CONCLUSION: The long-term treatment with orlistat may result in a small decline in the proportion of diet-derived fatty acids in serum lipid fractions when used in conjunction with low-fat diet.

Absence of cardiac valve dysfunction in obese patients treated with sibutramine.

OBJECTIVE: Serotonin-releasing agents prescribed as weight-loss medications have been implicated as a cause of acquired aortic and mitral valve abnormalities. Sibutramine hydrochloride (MERIDIA) is a serotonin and norepinephrine reuptake inhibitor with proven efficacy of weight reduction. The purpose of this study was to determine the incidence of cardiac valve disease in sibutraminetreated patients. RESEARCH METHODS AND PROCEDURES: Obese patients with type 2 diabetes mellitus enrolled in an ongoing double-blind, placebo-controlled, parallel-arm, 12-month study of sibutramine (followed by a 12-month open label extension) underwent transthoracic echocardiographic imaging and color Doppler interrogation for assessment of cardiac valve anatomy and function. RESULTS: A total of 210 patients were evaluated. Of these, 133 were receiving sibutramine (72 in the double-blind period), and 77 were receiving placebo. The mean+/-Standard Deviation age was 54+/-9 years, and the mean duration of treatment was 229+/-117 days (approximately 7.6 months). The prevalence of left-sided cardiac valve dysfunction was low and similar for the two treatment groups (sibutramine 3/133, or 2.3%; placebo 2/77, or 2.6%). All five cases were cases of aortic insufficiency; four were mild, one was severe (in a placebo patient). All three sibutramine cases were patients over age 50; two had a history of systemic hypertension. CONCLUSION: The prevalence of left-sided cardiac valve dysfunction was not higher than background in obese patients treated with sibutramine for an average of 7.6 months.

The economic and psychosocial consequences of obesity.

Obesity is a multifaceted problem with wide-reaching medical, social and economic consequences. These are partly determined by the wealth and disease pattern of the population. In less-developed societies overweight may be advantageous and socially acceptable. In affluent societies obesity is a well-recognized health hazard and a socially stigmatized condition. For the obese person, excess weight denotes an increased risk of disabling chronic diseases, lowered quality of life and loss of earnings. For the society, obesity is a major economic burden. Treatment costs of diseases directly attributable to obesity are estimated to correspond to about 4-5% of the total health care expenditure. The indirect costs arising from loss of productivity due to obesity may be even higher.

Food and mood: relationship between food, serotonin and affective disorders.

The relationship of food and eating with affective and other clinical disorders is complex and intriguing. Serotoninergic dysfunction in seasonal affective disorder, atypical depression, premenstrual syndrome, anorexia and bulimia nervosa, and binge eating disorder is reviewed. Patients exhibiting a relationship between food and behaviour are found in various diagnostic categories. This points to a need to shift from nosological to functional thinking in psychiatry. It also means application of psychopharmacological treatments across diagnostic boundaries. The use of phototherapy and psychotropic drugs (MAO inhibitors and selective serotonin reuptake inhibitors like fluoxetine) in these disorders is discussed.

Determinants of weight gain and overweight in adult Finns.

We studied sociodemographic and behavioural factors as predictors of weight gain in 12,669 adult Finns examined twice with a median interval of 5.7 years. The association of these factors with the prevalence of obesity (body mass index greater than or equal to 30 kg/m2) was also studied in a subsequent cross-sectional survey of 5673 Finns. In uni- and multivariate analyses, the risk of substantial weight gain (greater than or equal to 5 kg/5 years) was greatest for persons with a low level of education, chronic diseases, little physical activity at leisure or heavy alcohol consumption, and for those who got married or quit smoking between the examinations. Parity and energy intake predicted weight gain in women. The prevalence of obesity was inversely associated with the level of education and physical activity, and positively associated with alcohol consumption in men and parity in women. There were no significant differences in the prevalence of obesity by smoking or marital status. The recognition of socioeconomic and behavioural factors as important determinants of weight gain and overweight helps the planning of effective treatment and preventive programmes tailored for subjects at highest risk of obesity.

Familial occurrence of coronary heart disease according to clinical manifestation.

Occurrence of different clinical manifestations of coronary heart disease (CHD) was assessed among the parents and siblings of 309 men with CHD (case probands), including 103 men with fatal and 100 with nonfatal myocardial infarction (MI), and 106 men with angina pectoris (AP) and among the relatives of 106 reference men. CHD was equally common among relatives of all case probands. It was four times as common in case brothers and twice as common in case sisters as in the respective reference siblings. There were differences between the various case groups as to the predominant clinical manifestation of CHD. Cardiac deaths were commonest in the sibs of men with fatal MI, and uncomplicated angina in the men with AP. The familial resemblance in the clinical manifestations of CHD suggests familial influence in the mechanisms determining the clinical expression of the disease.

Identification of the high-risk groups in familial coronary heart disease.

Occurrence of coronary heart disease (CHD) was assessed among the sibs of 309 men with fatal or non-fatal CHD, including 126 men who developed the disease before age 46 (young patients), and 183 men who developed it at age 46-55 (middle-aged patients), and among the sibs of 212 reference men. The risk of early onset CHD was about 3 times as great for the sibs of the young as for those of the middle-aged patients. The risk was greatest of all, or up to 10-fold over the expected value, for the sibs of those young patients whose father or mother had died of CHD before age 70, but the risk was distinctly increased also for the sibs of the other young patients. By contrast, the sibs of the middle-aged patients carried an appreciably increased risk of early onset CHD only when one of the parents had died from CHD before age 70. Information about the family pattern of CHD is helpful in identifying the individuals at high risk for premature CHD.

Aggregation of coronary risk factors in families of men with fatal and non-fatal coronary heart disease.

The occurrence of main coronary risk factors was assessed in the families of 211 men under age 56 from East Finland. Fifty men were survivors of a recent myocardial infarction, 55 had died of myocardial infarction, 53 suffered from uncomplicated angina, and 53 were healthy reference men. Familial hyperlipidaemia was twice and familial hypertension three times as common in case as in reference families; other risk factors were equally common in both. Familial hypercholesterolaemia was commonest in the families of men with fatal myocardial infarction, and multiple type familial hyperlipidaemia in those of men with angina. Any increase in familial aggregation of coronary heart disease was invariably paralleled by increased aggregation of hyperlipidaemia and hypertension, with the most impressive aggregation of both traits in case families with a maternal history of early coronary death. It is concluded that most of the familial aggregation of coronary heart disease is mediated by familial aggregations of hyperlipidaemia and hypertension.

Familial aggregation of coronary heart disease in a high incidence area (North Karelia, Finland).

Occurrence of coronary heart disease was assessed in families of 211 men under the age of 56 from East Finland. Fifty men were survivors of recent myocardial infarctions, 55 had died of myocardial infarction, 53 suffered from uncomplicated angina pectoris, and 53 were healthy reference men. Overall prevalence of coronary heart disease was similar in familes of all case probands. By age 70, case fathers had a 6 times greater cumulative risk (a 36% chance) of dying from coronary heart disease than reference fathers, whereas there was only a small difference between case and reference mothers. Cumulative risk of developing fatal or non-fatal coronary heart disease by age 65 was 4.5-fold for case brothers (70%) and 2.6-fold for case sisters (40%), when compared with reference sibs. The risk was greatest for case sibs with a parental, especially a maternal, history of premature coronary heart disease. Clinical manifestations of coronary heart disease showed similarities within sibships. Cardiac deaths were commonest in sibs of the fatal myocardial infarction probands, whereas angina was commonest in sibs of the angina pectoris probands.

Familial occurrence of coronary heart disease: effect of age at diagnosis.

The occurrence of coronary heart disease and its main risk factors were assessed among the first degree relatives of 309 men from South and East Finland, including 203 men with fatal or nonfatal myocardial infarction and 106 healthy reference men under age 56 years. The younger the patient at the diagnosis of a first myocardial infarction, the more common was coronary heart disease in his parents and siblings. The risk of having coronary heart disease by age 55 was, respectively, 11.4, 8.3 and 1.3 times greater in the South and 6.7, 3.6 and 1.8 times greater in the East for the brothers of patients than for the brothers of reference subjects depending on whether the diagnosis of myocardial infarction in the patient had first been established before the age of 46 years of age 46 to 50 years or at age 51 to 55 years. Hypertension and hyperlipidemia, but none of the other risk factors studied, were most common among the relatives of the youngest patients and diminished in frequency with advancing age of the patient. Most of the strong familial component in coronary heart disease of early onset thus appears to be mediated by familial hyperlipidemias and hypertension. It is suggested that the risk of premature coronary heart disease in the persons at highest risk could be largely eliminated if information about family history were used to identify such persons at an early stage and if they were treated properly for their correctable risk factors.