The association between IGF-I and insulin resistance: a general population study in Danish adults.

OBJECTIVE: IGF-I has an almost 50% amino acid sequence homology with insulin and elicits nearly the same hypoglycemic response. Studies showed that low and high IGF-I levels are related to impaired glucose tolerance and to a higher risk of type 2 diabetes. The aim of the current study was to evaluate the association between IGF-I level and insulin resistance in a Danish general population. RESEARCH DESIGN AND METHODS: Included were 3,354 adults, aged 19-72 years, from the cross-sectional Health2006 study. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index to estimate insulin resistance. Serum IGF-I levels were determined by an immunoassay and grouped into quintiles (Q1-Q5). Linear or multinomial logistic regression analyses were performed. RESULTS: In the study population, 520 subjects (15.5%) had increased HOMA-IR values above 2.5. After adjustment for age, sex, physical activity, and waist-to-height ratio, a U-shaped association between IGF-I and HOMA-IR was found. Low IGF-I (Q1: odds ratio [OR] 1.65 [95% CI 1.16-2.34], P < 0.01) as well as high IGF-I (Q5: 1.96 [1.38-2.79], P < 0.01) levels were related to a higher odds of increased HOMA-IR values compared with subjects with intermediate (Q3) IGF-I levels. These associations remained statistically significant after the exclusion of subjects with type 2 diabetes and by using the updated computer HOMA2-IR model. CONCLUSIONS: Low- and high-normal IGF-I levels are both related to insulin resistance. The biological mechanism of this complex phenomenon has to be elucidated in more detail for future risk stratification.

Short-term changes of the urine metabolome after bariatric surgery.

Bariatric surgery leads to a loss of excess weight and to a remission of diabetes in a majority of patients. In an attempt to explain these underlying mechanisms, a broad range of metabolic alterations have been suggested. We aimed to investigate short-term changes in the urinary metabolome after bariatric surgery. Data for 50 patients who underwent bariatric surgery at the Municipal Hospital of Dresden-Neustadt, Germany, were used. Healthy controls were selected from the Study of Health in Pomerania. Non-fasting, spontaneous urine samples were collected, (1)H NMR spectroscopic analysis was performed, and metabolites were quantified (Chenomx NMR suite). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) models were carried out (pre-operative versus controls, and post-operative versus controls). On the basis of the urine metabolome separations between pre-operative (predictive ability Q2Y=85.6%; total explained variance R2X=58.3%), or post-operative (Q2Y=82.1%; R2X=44.4%) and controls were possible. Metabolites including hippuric acid, 3-hydroxybutyrate, 2-hydroxyisobutyrate, and trigonelline, were altered among patients. In obese patients, 2-hydroxyisobutyrate levels were higher, whereas trigonelline and hippuric acid levels were lower than in controls. The highest levels of 3-hydroxybutyrate were found in post-operative samples, whereas the metabolite was not present in controls, and only at low levels in pre-operative samples. In conclusion, we demonstrated that the urinary metabotype differs between obese patients and healthy controls. The metabolic alterations identified after bariatric procedures increase our knowledge about the metabolic traits associated with weight reduction. Whether urinary metabotypes might be used for early prediction of a successful bariatric procedure should be evaluated in long-term observations.