The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen.

OBJECTIVE: To evaluate the basal/total ratio of daily insulin dose (b/T) in outpatients with diabetes type 1 (DM1) and type 2 (DM2) on basal-bolus regimen, by investigating whether there is a relationship with HbA1c and episodes of hypoglycemia. METHODS: Multicentric, observational, cross-sectional study in Italy. Adult DM1 (n = 476) and DM2 (n = 541) outpatients, with eGFR >30 mL/min/1.73 m2, on a basal-bolus regimen for at least six months, were recruited from 31 Italian Diabetes services between March and September 2016. Clinicaltrials.govID: NCT03489031. RESULTS: Total daily insulin dose was significantly higher in DM2 patients (52.3 ± 22.5 vs. 46 ± 20.9 U/day), but this difference disappeared when insulin doses were normalized for body weight. The b/T ratio was lower than 0.50 in both groups: 0.46 ± 0.14 in DM1 and 0.43 ± 0.15 in DM2 patients (p = 0.0011). The b/T was significantly higher in the patients taking metformin in both groups, and significantly different according to the type of basal insulin (Degludec, 0.48 in DM1 and 0.44 in DM2; Glargine, 0.44 in DM1 and 0.43 in DM2; Detemir, 0.45 in DM1 and 0.39 in DM2). The b/T ratio was not correlated in either group to HbA1c or incidence of hypoglycemia (<40 mg/dL, or requiring caregiver intervention, in the last three months). In the multivariate analysis, metformin use and age were independent predictors of the b/T ratio in both DM1 and DM2 patients, while the type of basal insulin was an independent predictor only in DM1. CONCLUSION: The b/T ratio was independent of glycemic control and incidence of hypoglycemia.

Correction to: The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen.

[This corrects the article DOI: 10.1007/s40200-018-0358-2.].

Healthcare resource use, direct and indirect costs of hypoglycemia in type 1 and type 2 diabetes, and nationwide projections. Results of the HYPOS-1 study.

BACKGROUND AND AIMS: To obtain an accurate picture of the total costs of hypoglycemia, including the indirect costs and comparing the differences between type 1 (T1DM) and type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: HYPOS-1 was a multicenter, retrospective cohort study which analyzed the data of 2229 consecutive patients seen at 18 diabetes clinics. Data on healthcare resource use and indirect costs by diabetes type were collected via a questionnaire. The domains of inpatient admission and hospital stay, work days lost, and third-party assistance were also explored. Resource utilization was reported as estimated incidence rates (IRs) of hypoglycemic episodes per 100 person-years and estimated costs as IRs per person-years. For every 100 patients with T1DM, 9 emergency room (ER) visits and 6 emergency medical service calls for hypoglycemia were required per year; for every 100 patients with T2DM, 3 ER visits and 1 inpatient admission were required, with over 3 nights spent in hospital. Hypoglycemia led to 58 work days per 100 person-years lost by the patient or a family member in T1DM versus 19 in T2DM. The costs in T1DM totaled €90.99 per person-year and €62.04 in T2DM. Direct and indirect costs making up the total differed by type of diabetes (60% indirect costs in T1DM versus 43% in T2DM). The total cost associated with hypoglycemia in Italy is estimated to be €107 million per year. CONCLUSIONS: Indirect costs meaningfully contribute to the total costs associated with hypoglycemia. As compared with T1DM, T2DM requires fewer ER visits and incurs lower indirect costs but more frequent hospital use.

Growth hormone bioactivity and immunoactivity in tall children.

In subjects with constitutional tall stature, both low and high GH response to stimulation tests have been observed when measured by commercial kits. To investigate the reason for these conflicting results, we evaluated growth hormone (GH) secretion using different assays as well as GH-binding protein and insulin-like growth factor-I (IGF-I) concentrations in tall children. Serum samples were collected from 22 prepubertal constitutionally tall children, aged 2.87-13.25 years, during two pharmacological tests to evaluate serum GH levels measured by both immunofluorometric assay (IFMA) and the Nb2 cell bioassay. Serum IGF-I values were evaluated by RIA. Circulating low affinity (LA) and high affinity (HA) GH-binding proteins (GHBPs) were evaluated by FPLC gel filtration. Considering the highest serum GH levels as measured by IFMA, the 22 tall subjects were divided into two groups: group A including 16 children with blunted serum GH peak levels (5.78+/-0.68 ng/ml) and group B including 6 subjects with normal serum GH peak values (15.73+/-1.56 ng/ml). No differences were observed in serum GH peak levels as measured by the Nb2 cell bioassay between group A (14.77+/-1.54 ng/ml) and group B (16.03+/-1.96 ng/ml), and between both groups and 11 age-and sex-matched controls (12.25+/-1.19 ng/ml). In group A, the Nb2 cell bioassay/IFMA ratio of serum GH peak levels (0.29+/-0.08) was significantly higher (p<0.05) than in group B (0.07+/-0.01). No differences were found in serum LA-GHBP and HA-GHBP as well as in IGF-I concentrations between the 16 patients of group A and the 6 of group B. Likewise, no difference in auxological parameters was found between the two groups. The biological activity of GH evaluated using the Nb2 cell bioassay is similar in tall children with a low GH response as measured by IFMA in comparison with those with a normal GH response, and is in agreement with both the auxological data and serum IGF-I concentrations.

Growth hormone bioactivity, insulin-like growth factors (IGFs), and IGF binding proteins in obese children.

In obese children, both spontaneous and stimulated growth hormone (GH) secretion are impaired but a normal or increased height velocity is usually observed. This study was undertaken to explain the discrepancy between impaired GH secretion and normal height velocity. We evaluated the GH bioactivity (GH-BIO), GH serum level by immunofluorimetric assay (GH-IFMA), insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 in 21 prepubertal obese children (13 boys and eight girls) aged 5.7 to 9.4 years affected by simple obesity and in 32 (22 boys and 10 girls) age- and sex-matched normal-weight controls. The results were as follows (obese versus [v] controls): GH-IFMA, 4.84 +/- 3.54 v 23.7 +/- 2.04 microg/L (P < .001); GH-BIO, 0.60 +/- 0.45 v 1.84 +/- 0.15 U/mL (P < .001); IGF-I, 173.8 +/- 57.2 v 188.6 +/- 132.6 ng/mL (nonsignificant); IGF-II, 596.1 +/- 139.7 v 439.3 +/- 127.4 ng/mL (P < .001); IGFBP-1, 23.25 +/- 14.25 v 107 +/- 165.7 ng/mL (P < .05); IGFBP-2, 44.37 +/- 62.18 v 385.93 +/- 227.81 ng/mL (P < .001); IGFBP-3, 3.31 +/- 0.82 v 2.6 +/- 0.94 microg/mL (P < .05); and IGFs/IGFBPs, 1.32 +/- 0.32 v 1.07 +/- 0.34 (P < .05). In conclusion, in prepubertal obese children, not only immunoreactive but also bioactive GH concentrations were low. In these subjects, therefore, nutritional factors and insulin may contribute to sustain normal growth also by modulating several components of the IGF-IGFBP system.

Effect of low-dosage recombinant human growth hormone therapy on pulmonary function in hypopituitary patients with adult-onset growth hormone deficiency.

An impairment of the pulmonary function has been described in adult patients with childhood-onset growth hormone deficiency (GHD). We examined forced vital capacity (FVC), forced expiratory volume (FEV1), total lung capacity (TLC), functional residual capacity (FRC), residual volume (VR) and the index of inspiratory strength, middle tidal volume and tidal inspiratory time ratio (TV/I), in 29 patients with adult-onset GHD. Data were compared with those obtained in 46 healthy control subjects. Only the FEV1/FVC ratio was statistically different (p = 0.04) between the two groups of subjects. In a group of 15 GHD patients low dosages (0.5-1 IU/day s.c., bedtime) of recombinant human GH (rh-GH; n. = 8 subjects) or placebo (n. = 7) were given at random for a 6-month period. A significant increase in IGF-I levels was noted in the rh-GH-treated group (p = 0.04) but not in the placebo group. After the 6-month period no statistically significant changes in pulmonary function were found between the rh-GH-treated and placebo-treated GHD patients. This study shows that adult-onset GHD patients suffer from minimal impairment of pulmonary function. Low rh-GH dosages able to induce an increase in IGF-I levels do not improve pulmonary function. The effect of rh-GH on respiratory muscle strength could be related to the age at which GHD diagnosis is made, or induced only by high rh-GH dosages given for a long time.