Insulin resistance and obesity‐related factors in Prader–Willi syndrome: Comparison with obese subjects

Abstract

Prader-Willi syndrome (PWS), the most common genetic cause of marked obesity in humans, is usually due to a de novo paternally derived chromosome 15q11-q13 deletion or maternal disomy 15 [(uniparental disomy (UPD)]. Obesity is due to energy imbalance, but few studies have examined fat patterning and obesity-related factors in subjects with PWS (deletions and UPD) compared with subjects with simple obesity. We examined for differences in fatness patterning and lipid, leptin, and glucose and insulin levels in subjects with simple obesity and PWS and adjusted for gender, age, and body mass index (BMI). Fasting peripheral blood samples and cross-sectional magnetic resonance image scans at the level of the umbilicus were obtained in 55 subjects ranging in age from 10.4 to 49 years: 20 PWS deletion, 17 PWS UPD, and 18 obese controls. Subcutaneous fat area (SFA) and intra-abdominal visceral fat area (VFA) were calculated. No significant difference was seen between the PWS deletion subjects or PWS UPD subjects for fatness measurements or leptin levels. Twenty-three of 37 PWS subjects met the criteria for obesity (BMI > 95th percentile). No significant differences were observed for SFA and VFA between the PWS subjects judged to be obese and control subjects with simple obesity. There was an overall trend for decreased VFA in the PWS subjects but not significantly different. VFA was significantly positively correlated with both fasting insulin and total cholesterol in PWS deletion subjects but not in PWS UPD subjects or obese controls. Fasting insulin level was significantly lower in the obese PWS subjects compared with subjects with simple obesity, and insulin sensitivity (QUICKI) was significantly higher in PWS subjects with obesity. Homeostasis model assessment (HOMA) and QUICKI values were correlated and in opposite directions with triglycerides in the obese PWS subjects but not in the obese controls. Subjects in each group were stratified according to published criteria on the basis of their level of visceral fat (e.g. > or = 130 cm(2)) to assess the influence of VFA on metabolic abnormalities. In the obese PWS subjects, the fasting triglyceride, glucose, and insulin levels, and HOMA value were significantly elevated, while the QUICKI value was significantly lower in those with VFA > or = 130 cm(2). Such significant differences were not seen in the obese control group. Our results indicate that VFA may be regulated differently in PWS subjects compared to individuals with simple obesity. Insulin resistance is lower in PWS subjects and insulin sensitivity is higher compared with obese controls. PWS subjects with increased VFA may be at a higher risk of obesity-related complications compared to PWS subjects without increased VFA.

Circulating adiponectin levels, body composition and obesity-related variables in Prader–Willi syndrome: comparison with obese subjects

“…The obesity in PWS affects both the trunk and the limbs, 28 but a greater proportion of the abdominal fat is localized subcutaneously rather than around the visceral organs. 14,27 Our results are consistent with the hypothesis that excessive visceral, rather than subcutaneous, adiposity is particularly likely to be associated with decreased production and circulating levels of adiponectin. This could explain why PWS subjects with a greater percentage body fat have higher adiponectin levels, and why, in PWS individuals, there is a significant negative correlation between plasma adiponectin and waist-to-hip ratio, although Hoybye et al 15 did not report a significant negative correlation between adiponectin levels and waistto-hip ratios in their PWS subjects.…”

“…26 People with PWS may be less likely to develop diabetes mellitus or the metabolic syndrome than nonsyndromic people with comparable obesity. 14,27 Although our two groups of subjects (PWS and simple obesity) were matched for BMI, PWS subjects had a greater percentage body fat mass. The obesity in PWS affects both the trunk and the limbs, 28 but a greater proportion of the abdominal fat is localized subcutaneously rather than around the visceral organs.…”

In adults with Prader–Willi syndrome, elevated ghrelin levels are more consistent with hyperphagia than high PYY and GLP-1 levels

“…Interestingly, the two groups were also matched for central adiposity and insulin resistance without specific selection of control subjects. Although our PWS cohort might seem unusual, as a lower visceral fat mass and preserved insulin sensitivity has been reported previously (Brambilla et al, 1997, Goldstone et al, 2001, Goldstone et al, 2004, Goldstone et al, 2005, Talebizadeh and Butler, 2005, Kennedy et al, 2006, Theodoro et al, 2006, Haqq et al, 2010and Sode-Carlsen et al, 2010, other investigators recently reported similar observations to ours, i.e. obese children and adults with PWS having the same amount of visceral fat mass, the same degree of insulin resistance and a similar prevalence of metabolic syndrome compared to carefully weight-matched obese subjects Butler, 2005 andBrambilla et al, 2010).…”

“…2D). The postprandial meal response of GLP-1[active] was not statistically (Talebizadeh and Butler, 2005;Brambilla et al, 2010). The present study was not designed to compare body composition and fat distribution between PWS and obese subjects, as a larger cohort would be needed to that end.…”

An Update on Prader-Willi Syndrome with Diabetes Mellitus

“…PWS individuals may be less likely to develop T2DM than non-syndromic subjects with comparable obesity. In fact, the lower fasting insulin and HOMA-IR were shown in not only PWS children but also PWS adults 5,6) . However, recent study suggested further investigation with hyperinsulinemic-euglycemic clamp due to failure to reprove this identification 7) .…”