Development of hyperinsulinemia and insulin resistance during the early stage of weight gain

Obesity is associated with insulin resistance and hyperinsulinemia, which is considered to be a core component in the pathophysiology of obesity-related comorbidities. As yet it is unknown whether insulin resistance and hyperinsulinemia already develop during weight gain within the normal range. In 10 healthy male subjects the effect of intentional weight gain by 2 BMI points was examined on insulin. C-peptide and glucose levels following a meal, 75 g of glucose, and a two-step hyperglycemic clamp increased plasma glucose by 1.38 and 2.75 mmol/l, respectively. Baseline insulin, C-peptide, and glucose concentrations were significantly higher after weight gain from 21.8 to 23.8 kg/m(2) BMI within 4(1/2) mo. Calculations of insulin secretion and clearance indicate that reduced insulin clearance contributes more to post-weight gain basal hyperinsulinemia than insulin secretion. Following oral or intravenous stimulation insulin concentrations were significantly higher post-weight gain during all three test conditions, whereas C-peptide and glucose levels did not differ. Calculations of insulin secretion and clearance demonstrated that higher stimulated insulin concentrations are entirely due to clearance but not secretion. Despite significantly higher insulin levels, the rate of intravenous glucose required to maintain the defined elevation of glucose levels was either identical (1.38 mmol/l) or even significantly lower (2.75 mmol/l) following weight gain. The present study demonstrates for the first time that insulin resistance already develops during weight gain within the normal range of body weight. The associated basal and stimulated hyperinsulinemia is the result of differentiated changes of insulin secretion and clearance, respectively.     

Small weight gain is not associated with development of insulin resistance in healthy, physically active individuals.

We investigated whether weight gain alters insulin sensitivity and leptin levels in physically active individuals. Six (5 males and 1 female; age 26.6+/-1.0 years; BMI 21.5+/-0.9, body fat 17.4+/-2.2%) healthy individuals were enrolled in an overfeeding study (caloric surplus 22.5-26.5 kcal/kg/day) to achieve up to 10% weight gain over 4-6 week period with subsequent weight maintenance over additional 2 weeks. The participants were requested to maintain their previous physical activity which in all of them included 45-60 min training sessions at the gym 2-3 times/week. RESULTS: BMI increased to 23.4+/-0.9 (4.4 kg weight gain; p<0.05) and body fat to 21.0+/-2.8% (p < 0.05) over the period of active weight gain and remained stable over the two week period of weight maintenance; fasting plasma glucose and serum insulin remained unchanged; serum leptin nearly doubled (3.8+/-1.0 vs 6.4+/-1.9 ng/ mL; p < 0.05); insulin sensitivity, when expressed per kg of the total body (11.1+/-1.6 vs 12.4+/-2.1 mg/kg/min; p = NS), and lean body mass (13.4+/-1.9 vs 15.7+/-2.6 mg/kgLBM/min; p = NS), did not decrease after weight gain. On the contrary, insulin action had improved in 5 out of 6 individuals. In conclusion, the data presented in this preliminary report indicate that a small weight gain due to overfeeding in lean, healthy, physically active individuals is associated with rise in circulating leptin levels but not with worsening of insulin action.     

Fetal and infant growth and cardiovascular risk factors in women.

OBJECTIVE--To examine whether cardiovascular risk factors in women are related to fetal and infant growth. DESIGN--Follow up study of women born 1923-30 whose birth weights and weights at one year were recorded. SETTING--Hertfordshire. SUBJECTS--297 women born and still living in East Hertfordshire. MAIN OUTCOME MEASURES--Plasma glucose and insulin concentrations during a standard oral glucose tolerance test; fasting plasma proinsulin and 32-33 split proinsulin concentrations; blood pressure; fasting serum total, low density lipoprotein and high density lipoprotein cholesterol, triglyceride, and apolipoprotein A I and B concentrations; and plasma fibrinogen and factor VII concentrations. RESULTS--Fasting plasma concentrations of glucose, insulin, and 32-33 split proinsulin fell with increasing birth weight (P = 0.04, P = 0.002, and P = 0.0002 respectively, when current body mass index was allowed for). Glucose and insulin concentrations 120 minutes after an oral glucose load showed similar trends (P = 0.03 and P = 0.02). Systolic blood pressure, waist:hip ratio, and serum triglyceride concentrations also fell with increasing birth weight (P = 0.08, P = 0.07, and P = 0.07 respectively), while serum high density lipoprotein cholesterol concentrations rose (P = 0.04). At each birth weight women who currently had a higher body mass index had higher levels of risk factors. CONCLUSION--In women, as in men, reduced fetal growth leads to insulin resistance and the associated disorders: raised blood pressure and high serum triglyceride and low serum high density lipoprotein cholesterol concentrations. The highest values of these coronary risk factors occur in people who were small at birth and became obese. In contrast with men, low rates of infant growth did not predict levels of risk factors in women.     

Effect of a community-based weight management program on weight loss and cardiovascular disease risk factors

Objective: The purpose of our retrospective database analysis was to describe and evaluate the outcomes of a weight loss intervention in a community medical wellness center. Research Methods and Procedures: Four hundred eighteen overweight and obese adults entered the program between 2001 and 2004. Forty‐seven percent completed the 6‐month program designed using standards and recommendations established by the NIH, the American Dietetic Association, and the American Academy of Sports Medicine. Data analysis was limited to 198 participants (142 women, 56 men) completing the program. Results: Individuals completing the 6‐month program averaged a weight loss of 7.3% in men and 4.7% in women. Fasting lipids and blood glucose improved in both genders regardless of age. Outcomes including BMI and lipids improved in women regardless of menopausal status or hormone replacement therapy. There was a significant correlation between percentage weight loss and number of weekly counseling sessions attended and number of visits to the wellness center for exercise. Discussion: Participants who complete a structured community‐based weight management program can achieve significant weight loss and improvement in cardiovascular risk factors regardless of age, gender, or menopausal status. Our analysis suggests that national treatment guidelines/recommendations for weight management can be effectively implemented in a community medical wellness center. The relatively high drop‐out rate associated with this program suggests the need to identify strategies and techniques to enhance adherence and completion of programs.     

Birth weight correlates differently with cardiovascular risk factors in youth

Objective: Childhood obesity has become prevalent, resulting in a greater risk of hypertension, diabetes, and dyslipidemia. However, the relationship between these comorbid conditions and birth weight remains uncertain. We conducted this study to evaluate the relationship between birth weight and cardiovascular risk factors in children and adolescents. Research Methods and Procedures: In a nationwide survey conducted between 1992 and 2000, all schoolchildren 6 to 18 years old with glucosuria, proteinuria, or microscopic hematuria in repeated urine samples were included and received a physical examination and blood test. Those with gestational age <37 weeks were excluded. We enrolled 81,538 children (51,111 girls and 30,427 boys) and obtained their birth weights from the Taiwan Birth Registry. Obesity and hypertension were defined by age‐ and sex‐specific cut‐offs. Diabetes was diagnosed if the fasting glucose was >7 mM. Results: The risk of obesity was higher for those with birth weights ≥4000 grams [odds ratio (OR), 1.65] and 3543 to 3999 grams (OR, 1.28) and lower for those with birth weights 2601 to 2999 grams (OR, 0.90), using 3000 to 3542 grams as the reference group. An increased risk of diabetes was associated with both higher and lower birth weights, indicating a U‐shaped relationship (OR, <2600 grams, 1.607; 2601 to 2999 grams, 1.119; 3543 to 3999 grams, 1.112; ≥4000 grams, 1.661). In the 10‐ to 12‐year‐old age group, the risk of hypertension was higher in those with birth weights <2600 grams (OR, 1.20). Discussion: Low birth weight was associated with childhood diabetes. High birth weight was correlated with childhood obesity and diabetes. Our data indicate different relationships between birth weight and the development of obesity, hypertension, and diabetes in childhood.     

Assessing survey measures of infant birth weight and birth size in Ecuador

The purpose of this study was to assess the utility of using maternal assessments of infant birth size as proxy measures for birth weight in Ecuador, a country in which a sizeable proportion of births take place at home, where birth weight is typically not recorded. Four thousand and seventy-eight women who experienced a live singleton birth between January 1992 and August 1994 were interviewed in the Ecuador Demographic and Maternal-Child Health Survey. All women were asked if their child was weighed at birth, his/her weight, and what they considered to be his/her birth size relative to other newborns. The consistency between birth size and birth weight measures was assessed, and the differences between infants with and without reported birth weights were explored. The authors conclude that maternal assessments of birth size are poor proxy indicators of birth weight. Estimates of low birth weight based on maternal assessments of birth size as very small should be recognized as underestimates of the actual prevalence of low birth weight. Moreover, infants for whom birth weights are missing should not be considered similar to those for whom weight was reported. Those without reported birth weights are more likely to be low birth weight. Thus, relying solely on reports of numeric birth weight will underestimate the prevalence of low birth weight.     

An IGF-I promoter polymorphism modifies the relationships between birth weight and risk factors for cardiovascular disease and diabetes at age 36

BACKGROUND: Biochemical testing for pheochromocytoma by measurement of fractionated plasma metanephrines is limited by false positive rates of up to 18% in people without known genetic predisposition to the disease. The plasma normetanephrine fraction is responsible for most false positives and plasma normetanephrine increases with age. The objective of this study was to determine if we could improve the specificity of fractionated plasma measurements, by statistically adjusting for age. METHODS: An age-adjusted metanephrine score was derived using logistic regression from 343 subjects (including 33 people with pheochromocytoma) who underwent fractionated plasma metanephrine measurements as part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester (derivation set). The performance of the age-adjusted score was validated in a dataset of 158 subjects (including patients 23 with pheochromocytoma) that underwent measurements of fractionated plasma metanephrines at Mayo Clinic the following year (validation dataset). None of the participants in the validation dataset had known genetic predisposition to pheochromocytoma. RESULTS: The sensitivity of the age-adjusted metanephrine score was the same as that of traditional interpretation of fractionated plasma metanephrine measurements, yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%). However, the false positive rate with traditional interpretation of fractionated plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4%) and that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI, 1.2%, 7.4%) (p < 0.001 using McNemar's test). CONCLUSION: An adjustment for age in the interpretation of results of fractionated plasma metanephrines may significantly decrease false positives when using this test to exclude sporadic pheochromocytoma. Such improvements in false positive rate may result in savings of expenditures related to confirmatory imaging.     

Impact of cardiovascular risk factors on oxidative stress and DNA damage in a high risk Mediterranean population

Abstract

The impact of classic cardiovascular risk factors on oxidative stress status in a high-risk cardiovascular Mediterranean population of 527 subjects was estimated. Oxidative stress markers (malondialdehyde, 8-oxo-7′8′-dihydro-2′-deoxyguanosine, oxidized/reduced glutathione ratio) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) were analysed in circulating mononuclear blood cells. Malondialdehyde, oxidized glutathione and the ratio of oxidized to reduced glutathione were significantly higher while catalase and glutathione peroxidase activities were significantly lower in high cardiovascular risk participants than in controls. Statistically significant differences were obtained after additional multivariate control for sex, age, obesity, diabetes, lipids and medications. Among the main cardiovascular risk factors, hypertension was the strongest determinant of oxidative stress in high risk subjects studied at a primary prevention stage.     

Weight gain and cardiovascular risk factors during smoking cessation with bupropion or nicotine.

Weight gain is frequent after smoking cessation, and may limit patient's will to quit and long-term success. Nicotine and bupropion are effective drugs for smoking withdrawal. However, their influence on weight gain, insulin resistance and other cardiovascular risk factors, as well as possible differences in obese and lean subjects, have not been fully evaluated. We randomised 25 lean and 25 obese smokers to receive either bupropion or nicotine patches. Clinical evaluation and lipid profile were performed at baseline and after treatment. Insulin resistance was also assessed at the end. Weight, BMI, waist-to-hip ratio, and diastolic blood pressure increased (p < 0.005), whereas lipid profile improved (p < 0.001) after smoking cessation independently of obesity at baseline or drug used. Obese patients had higher insulin resistance at the end (p < 0.05) regardless of drug used. Weight gain was inversely related to age (beta= - 0.125, R = 0.38, p = 0.046), and insulin resistance was related to obesity at baseline (beta = 0.85, R = 0.46, p = 0.02). In conclusion, weight gain after smoking cessation is not dependent on obesity or drug taken. A beneficial lipid profile is achieved after quitting smoking with either bupropion or nicotine patch in both obese and lean subjects.     

Incidence of low birth weight infants born to mothers with multiple risk factors

Low birth weight (LBW) is associated with a large number and variety of risk conditions during pregnancy. The number and types of risk conditions per pregnancy were determined in 1,864 white and 872 black mothers delivered at the University of Kansas Medical Center between 1975 and 1978. The incidence of LBW infants increased steadily among white and black mothers as the number of risk factors increased from none to three or four per pregnancy. Among pregnancies without spontaneous premature rupture of membranes (PROM), 51 percent of the LBW infants were born to mothers who had multiple risk factors associated with their pregnancies, even though only 18 percent of these pregnancies were associated with multiple risk factors. Among pregnancies with PROM, 72 percent were associated with multiple risk conditions, and 31 percent resulted in LBW infants. About 90 percent of LBW infants from PROM pregnancies had mothers with multiple risk factors. For all numbers of risk conditions, black mothers had a higher incidence of LBW infants than white mothers. Among black mothers without spontaneous premature rupture of membranes (PROM), the incidence of LBW infants increased from 3.2 percent (10/308) in low (zero)-risk condition pregnancies to 33 percent (16/49) among mothers with three or four risk conditions during the pregnancy. Among white mothers without PROM, the incidence of LBW infants increased from 1.7 percent (12/708) in low (zero)-risk condition pregnancies to 30 percent (19/64) in pregnancies with three or four risk conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low birth weight: effect on insulin sensitivity and lipid metabolism

The metabolic and cardiovascular complications associated with reduced fetal growth have been identified during the past 10 years. These complications that encompass cardiovascular diseases and insulin resistance syndrome consist of dyslipidemia, impaired glucose tolerance or type 2 diabetes and appear to result from the initial development of insulin resistance. The association of reduced fetal growth with the other parameters of the syndrome X appear less constant than with insulin resistance and the expression and/or the age of onset seem to depend on the degree of genetic predisposition of the population. Although the mechanisms underlying the development of the insulin resistance associated with reduced fetal growth remain unclear, some evidence argues in favor of a key role of the adipose tissue. Several hypotheses have been proposed over the past 10 years to understand this unexpected association. Each of them points to either a detrimental fetal environment or genetic susceptibilities or interactions between these two components as playing a critical role in this context. Although not confirmed, the hypothesis suggesting that this association could be the consequence of genetic/environmental interactions remains at the moment the most attractive.     

Relation between birth weight at term and systolic blood pressure in adolescence.

OBJECTIVE--To examine whether birth weight is related to systolic blood pressure during adolescence. DESIGN--Retrospective (comparative) cohort study. The observers who traced and studied the subjects were unaware of their case-control status. SUBJECTS--330 subjects were born in Cardiff in 1975-7. Cases who were low birth weight at term (< 2500 g) were matched with controls of normal birth weight (3000-3800 g) at term. MAIN OUTCOME MEASURES--Systolic blood pressure measured by random zero sphygmomanometry in the subject''s right arm with the subject supine, corrected for size and age. RESULTS--The mean age at examination was 15.7 years. The mean systolic blood pressure of the cases was 105.8 mm Hg and of the controls 107.5 mm Hg. The corrected difference (95% confidence interval) in systolic blood pressure between the cases and controls was 1 mm Hg (-3 to +1 mm Hg; two tailed probability 0.33). CONCLUSION--Systolic blood pressure in adolescents of low birth weight is not significantly different from that of adolescents of normal birth weights.