What is an optimal diet? Relationship of macronutrient intake to obesity, glucose tolerance, lipoprotein cholesterol levels and the metabolic syndrome in the Whitehall II study

Abstract

OBJECTIVE: Saturated fats have adverse effects on health. To investigate which is more bene®cial for energy replacement, we compare the effects of polyunsaturated fatty acid and carbohydrate intake on obesity and metabolic variables (fasting triglycerides, HDL-cholesterol, LDL-cholesterol and 2 h glucose). Further, because the optimum diet may differ according to glucose tolerance, we examine the same associations in glucose tolerant and intolerant groups. Finally, we test the effect of macronutrient intake on the presence or absence of the metabolic syndrome. DESIGN: Cross-sectional analysis. SUBJECTS: A total of 4497 men and 1865 women aged 39 ± 62 in the Whitehall II study. RESULTS: In men, higher intakes of both polyunsaturated fats and carbohydrates were linked to lower waist ± hip ratio, triglycerides and LDL-cholesterol. Higher carbohydrate intake alone was linked to decreased body mass index (for 10 g higher carbohydrate intake, À0.12 kgam 2 , P`0.0001) and lower HDL-cholesterol (À0.01 mmolal, P`0.01). In normoglycaemic men, higher carbohydrate intakes were associated with higher 2 h insulin and glucose levels (0.25 pmolal, P`0.05 and 0.01 mmolal, P 0.001, respectively). Dietary effects among women were similar, the exception being a positive association of polyunsaturated fat intake with body mass index and waist ± hip ratio (0.47 kgam 2 , P`0.05 and 0.006, P`0.05, respectively). Dietary components, with the exceptions of cholesterol and protein in men, were unrelated to prevalence of the metabolic syndrome, and adjustment for differences in macronutrient intake did not account for the strong inverse association between socioeconomic position and the metabolic syndrome. CONCLUSION: Our observational data provide evidence that both polyunsaturated fatty acids and carbohydrates offer small metabolic bene®ts with few adverse effects compared with saturated fats.

Diabesity: A Polygenic Model of Dietary-Induced Obesity from Ad Libitum Overfeeding of Sprague–Dawley Rats and Its Modulation by Moderate and Marked Dietary Restriction

“…The risk of developing diabetes increases in an exponential manner with increasing BMI. Even moderate weight excess is considered a significant risk factor for multiple diabetes co-morbidities (Whitaker et al, 1997;Brunner et al, 2001;Eckel et al, 2002;Konstantinov, 2003;Pasquale et al, 2003;Rauser et al, 2003;Hu et al, 2004;Lazar, 2005). The adverse effects of such excess weight on blood glucose control are attributed to insulin resistance, and obese patients with diabetes have a higher prevalence of other risk factors, including cardiovascular and renal disease, hypertension and dyslipidemias.…”

“…Furthermore, in North America, losing weight is estimated to prevent 1 in 6 cancer deaths, or more than 90,000 per year. It is estimated that excessive weight and obesity in the United States could account for 14% of all cancer deaths in men and 20% in women (Brunner et al, 2001;Bray, 2002;Eckel et al, 2002;Konstantinov, 2003). Since the human populations suffering the sequelae of diabesity are heterozygous populations, this phenotype is clearly the result of polygenic trait loci that interact in complex ways with environmental factors, but can be readily controlled and managed by behavioral and exercise therapy and moderate dietary or caloric restriction of food intake.…”

“…Approximately 1 in 5 U.S. adults have metabolic syndrome (syndrome X or diabesity) which is manifest as a cluster of metabolic abnormalities identified by three or more changes including abdominal obesity, hypertriglyceremia, low HDL cholesterol, high blood pressure and high fasting glucose (Whitaker et al, 1997;Brunner et al, 2001;Eckel et al, 2002;Konstantinov, 2003). The potential morbidity and mortality consequences of this polygenic syndrome in the general population cry out for a reliable polygenic rodent Vol.…”

“…The adverse effects of such excess weight on blood glucose control are attributed to insulin resistance, and obese patients with diabetes have a higher prevalence of other risk factors, including cardiovascular and renal disease, hypertension and dyslipidemias. This segregation of risk factors known as metabolic syndrome, insulin-resistant syndrome, or syndrome X, explains the very high cardiovascular and renal morbidity and mortality rates in the population of humans and rodents with adult-onset type 2 diabetes and obesity, or diabesity (Whitaker et al, 1997;Brunner et al, 2001;Eckel et al, 2002;Leiter, 2002;Axen et al, 2003;Konstantinov, 2003). In humans it appears that obese individuals prone to develop defective blood glucose control and insulin secretion will develop overt type 2 diabetes due to a complex interaction of genetic predispositions and environmental factors of which uncontrolled food intake inducing excessive body weight gain is a key factor.…”

“…It is considered one of the best outbred SD rat stocks and is commonly used in behavioral, nutritional, reproductive, teratological, toxicological, and carcinogenicity testing worldwide. Adult-onset human or animal type 2 diabetes associated with obesity (diabesity) is induced by a complex set of genetic, dietary and environmental interactions (Weindruch and Walford, 1988;Klinger et al, 1996;Brunner et al, 2001;Eckel et al, 2002;Bray, 2002). For example, monogenic obesity mutations in rodents such as those in the leptin gene (Lep ob , ob/ob mice) or its receptor gene (Lepr db , db/db mice, Lepr fa fa/fa Zucker rats or Lepr cp cplcpJCR rats) have been extremely useful in the study of these processes and useful in efficacy testing of anti-obesity and antidiabetic drugs (Harrison and Archer, 1987;Lee and Yu, 1990;Lu et al, 1991;Leiter, 2002;Inui et al, 2004;Park and Prolla, 2005).…”