Objective: Increase of resistin and/or reduction of adiponectin have been implicated in the development of insulin resistance following weight gain. We aimed to study this prospectively in humans. Design: Prospective and interventional with parallel control group. Methods: Twelve healthy men and six healthy women (age 26G6.6 years) and an age-matched control group were recruited. Subjects in the intervention group aimed for a bodyweight increase of 5-15% by doubling the baseline caloric intake by eating at least two fast food-based meals a day in combination with adoption of a sedentary lifestyle for 4 weeks. Results: Bodyweight increased from 67.6G9.1 to 74.0G11 kg, P!0.001, by the intervention. Insulin levels increased (before: 27.4G12 pmol/l, after: 53.0G22 pmol/l, PZ0.004), while plasma levels of adiponectin (before: 5038G3736 ng/ml, after: 6739G7949 ng/ml, PZ0.18) and resistin (before: 21.8G19 ng/ml, after: 14.4G6.8 ng/ml, PZ0.074) remained unchanged by the weight gain and were similar as in controls. On the other hand, leptin levels increased about threefold following the intervention (before: 5.7G7.4, after: 16G20 ng/ml, PZ0.008), and also the inflammatory marker C-reactive protein (CRP) increased from 0.34G0.44 to 0.71G0.87 mg/l, PZ0.03, when two outliers O10 mg/l were disregarded. Conclusions: Hyperalimentation reduces insulin sensitivity when weight gain of 9% was combined with reduction of exercise. However, the levels of resistin and adiponectin were unaffected by the intervention, while CRP levels increased within this short time period suggesting that low-grade inflammation can occur early in the process of developing a metabolic syndrome.

The interaction of the PPARγ Pro12Ala polymorphism with diabetes and cardiovascular risk is controversial. We studied 173 women and 309 men in the observational CARDIPP trial in which determination of left ventricular mass, carotid intima-media thickness (IMT), and pulse-wave velocity (PWV) were performed. Blood pressures were measured with 24-hour ambulatory technique (ABP). Heterozygotes and homozygotes of Ala were defined as Ala in the analyses. Men with Ala-isoform displayed higher waist circumference (Ala: 107±14 cm, Pro: 104±11 cm, p=0.045) and body weight (Ala: 95.7±18 kg, Pro: 91.6±14 kg, p=0.042) than Pro-homozygotes. Men with ALA-isoform also showed higher systolic ABP levels (Ala: 134±15 mmHg, Pro: 130±14 mmHg, p=0.004) while left-ventricular mass-index, IMT and PWV were unrelated to isoforms. In contrast, carotid-radial PWV was lower in women with the Ala-isoform (Ala: 7.9±1.0 m/s, Pro: 8.5±1.3 m/s, p=0.01) and levels of apolipoprotein A1 were higher (Ala: 1.43±0.27 g/l, Pro: 1.35±0.17 g/l, p=0.03). In conclusion we found that men with type 2 diabetes having the Ala-isoform of PPARγ Pro12Ala had an unfavorable cardiovascular risk profile while women with this isoform had lower carotid-radial PWV and higher apolipoprotein A1 levels suggesting a beneficial prognosis. These differences according to gender of the ALA isoform in type 2 diabetes deserve further attention.