Addition of insulin glargine or NPH insulin to metformin monotherapy in poorly controlled type 2 diabetic patients decreases IGF-I bioactivity similarly

Aims/hypothesis The aim of this study was to compare IGFI bioactivity 36 weeks after the addition of insulin glargine (A21Gly,B31Arg,B32Arg human insulin) or NPH insulin to metformin therapy in type 2 diabetic patients who had poor glucose control under metformin monotherapy. Methods In the Lantus plus Metformin (LANMET) study, 110 poorly controlled insulin-naive type 2 diabetic patients were randomised to receive metformin with either insulin glargine (G+MET) or NPH insulin (NPH+MET). In the present study, IGF-I bioactivity was measured, retrospectively, in 104 out of the 110 initially included LANMET participants before and after 36 weeks of insulin therapy. IGF-I bioactivity was measured using an IGF-I kinase receptor activation assay. Results After 36 weeks of insulin therapy, insulin doses were comparable between the G+MET (68±5.7 U/day) and NPH+MET (71±6.2 U/day) groups (p=0.68). Before insulin therapy, circulating IGF-I bioactivity was similar between the G+MET (134±9 pmol/l) and NPH+MET (135 ±10 pmol/l) groups (p=0.83). After 36 weeks, IGF-I bioactivity had decreased significantly (p=0.001) and did not differ between the G+MET (116±9 pmol/l) and NPH+MET (117± 10 pmol/l) groups (p=0.91). At baseline and after insulin therapy, total IGF-I concentrations were comparable in both groups (baseline: G+MET 13.3±1.0 vs NPH+MET 13.3± 1.0 nmol/l, p=0.97; and 36 weeks: 13.4±1.0 vs 13.1± 0.9 nmol/l, p=0.71). Total IGF-I concentration did not change during insulin therapy (13.3±0.7 vs 13.3±0.7 nmol/l, baseline vs 36 weeks, p=0.86). Conclusions/interpretation Addition of insulin glargine or NPH insulin to metformin monotherapy in poorly controlled type 2 diabetic patients decreases serum IGF-I bioactivity in a similar manner

Serum free and total insulin-like growth factor-1, insulin-like growth factor binding protein-1 and insulin-like growth factor binding protein-3 levels in healthy elderly individuals - Relation to self-reported duality of health and disability

Background: Little is known about the influence of the free insulin-like growth factor-I/insulin-like growth factor binding protein (IGF-I/IGFBP) system on the quality of health and on disability in the elderly population. Design: In a cross-sectional population based study of 218 healthy elderly subjects (age 55-80 yrs) fasting free and total insulin-like growth factor (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels were measured. Subjective quality of health was assessed by asking all participants whether they judged the quality of their health as better, the same or worse than that of their peers. Disability was determined by the Disability Index of the Stanford Health Questionnaire. Results: Mean serum-free IGF-I levels were significantly lower in the 21 subjects who experienced their health as worse than those of their peers, compared to the 181 subjects who experienced their health as better or the same as their peers 0.069 (SE 0.009) vs. 0.093 nmol/l (SE 0.004) (p = 0.04). Mean IGFBP-1 levels were significantly higher in subjects, who felt less healthy than their peers 1.23 (SE 0.26) vs. 0.73 nmol/l (SE 0.82) (p = 0.01). Free and total IGF-I, IGFBP-1 and IGFBP-3 levels, were not different in subjects with the lowest and the highest Disability Index Score. Conclusion: Low free IGF-I and high IGFBP-1 levels are associated with a decreased self-reported quality of health, but are not related to physical disability in the elderly

Serum tree IGF-I, total IGF-I, IGFBP-1 and IGFBP-3 levels in an elderly population:relation to age and sex steroid levels

BACKGROUND Most previous studies concerning the relationship between IGF-I and age used assays measuring total IGF-I, Although free IGF-I is considered of greater biological relevance, little is known about its relationship with sex steroids levels in elderly healthy subjects, MEASUREMENTS In a cross-sectional study of 218 healthy people (103 men, 115 women) aged 55-80 years we measured serum total and free IGF-I, IGFBP-1 and IGFBP3 levers and sex steroids. Free androgen index and free oestradiol index were used as an indicator for free oestradiol and free testosterone levels, respectively. RESULTS Free IGF-I revels did not decline with age in the whole study population. Free IGF-I levels even increased in individuals above 70 years of age in comparison to those aged between 55 and 70 years (mean +/- SE 0.106 +/- 0.007 nmol/l vs, 0.086 +/- 0.004 nmol/l, P = 0.009). Total IGF-I and IGFBP-3 decreased with age (r = -0.20, P = 0.005 and r = -0.24, P = 0.001, respectively). Total IGF-I levels were positively related with free oestrogen index in both sexes. Free IGF-I did not relate to free oestrogen or androgen index. In women only, free IGF-I was related positively with DHEAS while IGFBP-1 was inversely correlated with DHEAS. CONCLUSIONS Free IGF-I levels do not decrease with age and are even higher in individuals above 70 years. There was no relationship between free IGF-I and free androgen or oestrogen index in either gender. We hypothesize that higher free IGF-I levels in older persons may be the consequence of selective survival in the cohort: subjects with high free IGF-I levels may live longer. The absence of a relationship between free IGF-I levels and free androgen and oestrogen indices suggests that there is no direct interaction between the biological activity of circulating IGF-I levels and sex hormone production in a healthy ageing population