Endocrine Abstracts

Low insulin-like growth factor-II (IGF-II) concentration predicts weight gain in normal weight subjects with type 2 diabetes

AH Heald¹, L Karvestedt², SG Anderson¹, J McLaughlin¹, A Knowles³, L Wong¹, A White⁴, K Brismar² & M Gibson¹

¹Department of Endocrinology, Salford Royal Hospitals NHS Trust, Salford, UK; ²Department of Endocrinology and Diabetology, Karolinska Hospital, Stockholm, Sweden; ³Diabetes Centre, Manchester Royal Infirmary, Manchester UK; ⁴Endocrine Sciences, University of Manchester Medical School, Manchester, UK.

Introduction

Insulin-like growth factors-I (IGF-I) and -II (IGF-II) are important in regulation of metabolism and growth. We previously reported in normal weight normoglycaemic individuals that low circulating IGF-II predicts future weight gain. We subsequently investigated whether such relationships persisted in circumstances of abnormal glucose tolerance.

Method

In 224 type 2 diabetes subjects we assessed the association between baseline IGF-II levels and risk of weight gain (> 2.0 kg) at 5 year follow-up. The mean age of the participants at follow-up was 64.8 (95% CI 63.9-65.7) years.

Results

At follow-up 90 participants (40.2%) gained more than 2.0 kg body weight. For normal weight subjects (BMI 25 or less) at baseline, mean IGF-II levels were significantly lower in those who gained > 2kg weight than weight stable subjects 454 (95 % CI 349-559) ng/ml ng/ml vs 620 (534-705) ng/ml, F=7.4, p=0.01. Multivariate ANOVA indicated that this difference was independent of baseline fasting insulin C-peptide, glucose, IGF-I, treatment and duration of diabetes (F=6.3, p=0.02). For this subgroup low circulating IGF-II at baseline strongly correlated with weight gain (Spearman's rho= -0.55, p<0.001). With increasing weight the relationship progressively weakened so that for individuals with BMI greater than 27 no relationship between low IGF-II and future weight gain was found. Logistic regression showed that for BMI 25 or less individuals at baseline, for each 100 ng/ml increase in circulating IGF-II there was a 22% decreased risk of gaining 2.0 kg or more in weight by 5 years follow-up.

Conclusion

Our data show that in normal weight type 2 diabetes subjects, baseline IGF-II concentration is inversely related to future weight gain, strengthening the putative role for IGF-II in regulating fat mass. The diminishing strength of the relationship as BMI increases suggests that adipocyte derived factors may disrupt the capacity of IGF-II to regulate fat mass as adiposity increases.

Endocrine Abstracts (2005) 9 P3