Christina A. Hedman

Elevated circulating adiponectin in type 1 diabetes is associated with long diabetes duration

Objective  To study circulating adiponectin concentrations in relation to diabetes duration and endogenous insulin secretion in patients with type 1 diabetes.

Treatment with insulin lispro changes the insulin profile but does not affect the plasma concentrations of IGF‐I and IGFBP‐1 in type 1 diabetes

OBJECTIVE IGF‐I levels in patients with type 1 diabetes without endogenous insulin production are low. Our aim was to examine whether the plasma insulin profile obtained by treatment with the insulin analogue lispro has a different effect on plasma concentrations of IGF‐I and IGFBP‐1 than that seen during treatment with conventional human insulin (regular insulin).

Intraperitoneal insulin delivery to patients with type 1 diabetes results in higher serum IGF‐I bioactivity than continuous subcutaneous insulin infusion

Type 1 diabetes (T1D) is associated with low IGF‐I and altered levels of IGF‐binding proteins (IGFBPs) in plasma. This may be of importance for insulin sensitivity and the risk of developing diabetic complications. We hypothesized that IGF‐I bioactivity is affected by the route of insulin administration and that continuous intraperitoneal insulin infusion (CIPII) has a more pronounced effect than continuous subcutaneous insulin infusion (CSII).

Different Effects of Intraperitoneal and Subcutaneous Insulin Administration on the GH-IGF-1 Axis in Type 1 Diabetes

CONTEXT In type 1 diabetes mellitus, low levels of insulin-like growth factor -1 (IGF-1) and IGF binding protein-3 (IGFBP-3) and high levels of GH and IGFBP-1 are present, probably due to portal vein insulinopenia. OBJECTIVE To test the hypothesis that continuous ip insulin infusion (CIPII) has a more pronounced effect than sc insulin therapy on regulation of the GH-IGF-1 axis. DESIGN This was a prospective, observational case-control study. Measurements were performed twice at a 26-week interval. SETTING Two secondary care hospitals in the Netherlands participated in the study. PATIENTS There were a total of 184 patients, age- and gender-matched, of which 39 used CIPII and 145 sc insulin therapy for the past 4 years. OUTCOMES Primary endpoint included differences in IGF-1. Secondary outcomes were differences in GH, IGFBP-1, and IGFBP-3. RESULTS IGF-1 was higher with CIPII as compared to SC insulin therapy: 124 μg/liter (95% confidence interval [CI], 111-138) vs 108 μg/liter (95% CI 102-115) (P = .035). Additionally, IGFBP-3 concentrations were higher and IGFBP-1 and GH concentrations were lower with CIPII as compared to SC insulin therapy: 3.78 mg/liter (95% CI, 3.49-4.10) vs 3.31 mg/liter (95% CI, 3.17-3.47) for IGFBP-3, 50.9 μg/liter (95% CI, 37.9-68.2) vs 102.6 μg/liter (95% CI, 87.8-119.8) for IGFBP-1 and 0.68 μg/liter (95% CI, 0.44-1.06) vs 1.21 μg/liter (95% CI, 0.95-1.54) for GH, respectively. In multivariate analysis, IGF-1 had no significant association with HbA1c. CONCLUSIONS The GH-IGF-1 axis may be affected by the route of insulin administration with CIPII counteracting dysregulation of the GH-IGF1 axis present during sc insulin therapy.

After 6 years of intraperitoneal insulin administration IGF-I concentrations in T1DM patients are at low-normal level

OBJECTIVE Low concentrations of insulin-like growth factor-I (IGFI) have been reported in type 1 diabetes mellitus (T1DM), suggested to be due to low insulin concentrations in the portal vein. The aim was to describe the long-term course of IGFI concentrations among T1DM subjects treated with continuous intraperitoneal (IP) insulin infusion (CIPII). DESIGN Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) insulin therapy in 2006 were followed until 2012. IGF-I measurements were performed at the start of the 2006 study, after the 6 month SC- and CIPII treatment phase in 2006 and during CIPII therapy in 2012. Z-scores were calculated to compare the IGF-I concentrations with age-specific normative range values of a non-DM reference population. RESULTS In 2012, IGF-I Z-scores (-0.7; 95% confidence interval -1.3, -0.2) were significantly higher than at the start of the 2006 study (-2.5; -3.3, -1.8), the end of the SC (-2.0; -2.6, -1.5) and CIPII (-1.6; -2.1, -1.0) treatment phase with a mean difference of: 1.8 (0.9, 2.7), 1.3 (0.5, 2.1) and 0.8 (0.1, 1.6), respectively. CONCLUSION After 6 years of treatment with CIPII, IGF-I concentrations among T1DM patients increased to a level that is higher than during prior SC insulin treatment and is in the lower normal range compared to a non-DM reference population. The results of this study suggest that long-term IP insulin administration influences the IGF system in T1DM.

Upper extremity impairments in type 1 diabetes with long duration; common problems with great impact on daily life

Abstract Purpose: To investigate the prevalence, activity limitations and potential risk factors of upper extremity impairments in type 1 diabetes in comparison to controls. Methods: In a cross-sectional population-based study in the southeast of Sweden, patients with type 1 diabetes <35 years at onset, duration ≥20 years, <67 years old and matched controls were invited to answer a questionnaire on upper extremity impairments and activity limitations and to take blood samples. Results: Seven hundred and seventy-three patients (ages 50 ± 10 years, diabetes duration 35 ± 10 years) and 708 controls (ages 54 ± 9 years) were included. Shoulder pain and stiffness, hand paraesthesia and finger impairments were common in patients with a prevalence of 28–48%, which was 2–4-folds higher than in controls. Compared to controls, the patients had more bilateral impairments, often had coexistence of several upper extremity impairments, and in the presence of impairments, reported more pronounced activity limitations. Female gender (1.72 (1.066–2.272), p = 0.014), longer duration (1.046 (1.015–1.077), p = 0.003), higher body mass index (1.08 (1.017–1.147), p = 0.013) and HbA1c (1.029 (1.008–1.05), p = 0.007) were associated with upper extremity impairments. Conclusions: Compared to controls, patients with type 1 diabetes have a high prevalence of upper extremity impairments, often bilateral, which are strongly associated with activity limitations. Recognising these in clinical practise is crucial, and improved preventative, therapeutic and rehabilitative interventions are needed. Implications for rehabilitation Upper extremity impairments affecting the shoulder, hand and fingers are common in patients with type 1 diabetes, the prevalence being 2–4-fold higher compared to non-diabetic persons. Patients with diabetes type 1 with upper extremity impairments have more pronounced limitations in daily activities compared to controls with similar impairments. Recognising upper extremity impairments and activity limitations are important and improved preventive, therapeutic and rehabilitation methods are needed.

Dysregulated growth hormone-insulin-like growth factor-1 axis in adult type 1 diabetes with long duration

In type 1 diabetes (T1D), dysregulation of the GH‐IGF‐1 axis has been reported. Whether this is related to upper extremity impairments (UEI) is unknown.