The longitudinal association between glycaemic control and health-related quality of life following insulin therapy optimisation in type 2 diabetes patients. A prospective observational study in secondary care.

PURPOSE: To test whether improvement in glycosylated haemoglobin (HbA(1c)) as a marker of glycaemic control, following intensifying insulin therapy, is associated with improvements in HRQoL. METHODS: Dutch sub-optimally controlled (HbA(1c) > 7%) type 2 diabetes patients (N = 447, mean age 59 ± 11) initiated insulin glargine therapy. Data were collected at baseline, 3 and 6 months, and included HbA(1c) and measures of HRQoL: diabetes symptom distress (Diabetes Symptom Checklist-revised; DSC-r), fear of hypoglycaemia (Hypoglycaemia Fear Survey; HFS-w) and emotional well-being (WHO-5 wellbeing index). RESULTS: HbA(1c) decreased from 8.8 ± 1.4% to 8.0 ± 1.2% and 7.7 ± 1.3% at 3 and 6 months follow-up, respectively (P < 0.001), DSC-r score improved from 17.7 ± 14.7 to 14.3 ± 13.3 and 13.6 ± 13.3 (P < 0.001). HFS-w score did not significantly change. WHO-5 score increased from 56 ± 23 to 62 ± 23 and 65 ± 22 P < 0.001). A modest, significant association was found between HbA(1c) and WHO-5 score (B = -1.8, 95% CI: -2.7 to -0.8) and HbA1c and DSC-r score (B = 1.0, 95% CI: 0.4 to 1.6). No such association was found for HFS-w score. CONCLUSIONS: An association between improvement in HbA(1c) by means of optimising insulin therapy and improvement in HRQoL in type 2 diabetes patients has been observed. A weak, yet significant longitudinal association was found between improved HbA(1c) and emotional well-being and diabetes symptom distress.

Initiation of insulin glargine in patients with Type 2 diabetes in suboptimal glycaemic control positively impacts health-related quality of life. A prospective cohort study in primary care.

AIMS: To study prospectively the impact of initiating insulin glargine in suboptimally controlled insulin-naïve patients with Type 2 diabetes on health-related quality of life in relation to glycaemic control. METHODS: Insulin-naïve Dutch patients with Type 2 diabetes in suboptimal glycaemic control (HbA(1c) > 53 mmol/mol; 7%) on maximum dose of oral glucose-lowering medications were included from 363 primary care practices (n = 911). Patients started insulin glargine and were followed up for 6 months. At baseline (start insulin therapy), 3 and 6 months, HbA(1c) was measured and patients completed self-report health-related quality of life measures, including emotional well-being (World Health Organization-5 well-being index), fear of hypoglycaemia (Hypoglycaemia Fear Survey) and diabetes symptom distress (Diabetes Symptom Checklist-revised). Data were analysed using generalized estimating equations analysis. RESULTS: HbA(1c) (mmol/mol; %) decreased from 69 ± 16; 8.5 ± 1.7 to 60 ± 11; 7.6 ± 1.0 and 57 ± 11; 7.3 ± 1.0 at 3 and 6 months, respectively (P < 0.001). Pre-insulin BMI (kg/m(2) ) was 30 ± 5.7, which remained stable at 3 months (30 ± 5.8) and increased to 31 ± 5.9 at 6 months (P = 0.004); no significant changes in self-reported symptomatic and severe hypoglycaemia were observed, while nocturnal hypoglycaemia slightly decreased. The Hypoglycaemia Fear Survey score decreased from 14.6 ± 16.2 to 12.1 ± 15.2 and 10.8 ± 14.4 at 3 and 6 months, respectively (P < 0.001). The Diabetes Symptom Checklist-revised score decreased from 15 ± 14 to 10 ± 12 and 10 ± 13 (P < 0.001), with most pronounced reductions in hyperglycaemic symptoms and fatigue. The World Health Organization-5 score increased from 57 ± 25.3 to 65 ± 21.6 at 3-month follow-up and 67 ± 21.8 at 6-month follow-up (P < 0.001). CONCLUSIONS: Results of this observational study demonstrate combined glycaemic and health-related quality of life benefits of initiating insulin glargine in patients with Type 2 diabetes in routine primary care.

Neutrophil, glass-adherent, nitroblue tetrazolium assay gives early indication of immunization effectiveness in rainbow trout.

Neutrophil activity in rainbow trout (Oncorhynchus mykiss) is increased upon antigenic stimulation with the Yersinia ruckeri O-antigen bacterin. The characteristics of neutrophil attachment to glass and nitroblue tetrazolium (NBT) staining were used to determine the effectiveness of immunization programs with fingerling rainbow trout. Fish immunized by intraperitoneal injection with doses of 100, 10, or 1 microgram of the bacterin showed the highest responses in that order in numbers of glass adherent, NBT-positive neutrophils. Studies on the kinetics of the occurrence of numbers of glass-adherent, NBT-positive staining cells from the fish injected with the 10 micrograms dose showed the numbers of positive cells were largest on Day 2 after injection. The specific immune response was confirmed by demonstrating the presence of plaque-forming cells by the passive hemolytic plaque assay and the rise in humoral antibody titers by passive hemagglutination 12 days after injection. The effects of immunization in trout could be detected earlier by using the neutrophil glass adherence and NBT reduction assays than by using assays based on observations of the specific immune response.

Murine macrophage precursor cell lines are unable to differentiate into osteoclasts: a possible implication for osteoclast ontogeny.

Six murine macrophage precursor cell lines, thought to be arrested around the CFU-GM stage of the myeloid differentiation and shown to be negative for acid phosphatase, F4/80 antigen expression and phagocytosis capacity, were tested for their ability to differentiate into osteoclasts. Their differentiation potential was compared with that of the haemopoietic stem cell line FDCP-mix C2GM. None of the macrophage precursor cell lines could be induced to differentiate into osteoclasts when the cells were cocultured with either periosteum-free metatarsal bones of fetal mice, or monolayers of osteoblast-like cells. In contrast, when the haemopoietic stem cell line FDCP-mix C2GM, murine fetal liver cells or murine spleen cells were used as a source of haemopoietic precursor cells, numerous osteoclasts were formed in both culture systems. During cell culture a small percentage of the macrophage precursor cells attached to the bottom of the culture well. These firmly attached cells acquired acid phosphatase activity, F4/80 antigen expression and phagocytosis capacity. Furthermore, when the cell lines were cultured for 2 or 4 days with 1% DMSO, up to 30% of the precursor cells differentiated into metamyelocytes. These results suggest that the macrophage precursor cell lines are able to acquire macrophage and granulocyte characteristics, but are unable to differentiate into osteoclasts. In contrast, the haemopoietic stem cell line FDCP-mix C2GM is able to differentiate into both macrophages and osteoclasts. We therefore suggest that the osteoclast lineage branches off at an early stage of the myeloid differentiation pathway.

The role of osteoblast density and endogenous interleukin-6 production in osteoclast formation from the hemopoietic stem cell line FDCP-MIX C2GM in coculture with primary osteoblasts.

Osteoclast formation from the hemopoietic stem cell line FDCP-mix C2GM was shown to be strongly dependent on osteoblast density. In cocultures of C2GM cells with fetal mouse osteoblasts seeded at high density (i.e., 2.5 x 10(4) cells/cm2), we found a significantly lower osteoclast formation compared with cocultures with osteoblasts seeded at low density (i.e., 1 x 10(4) cells/cm2). The differentiation state of osteoblasts in high-density cultures resembled more than that of osteoblasts in low-density cultures, the differentiation state of mature osteoblasts, since the cells in the former cultures showed higher alkaline phosphatase (APase) activity than the cells in the latter cultures, and nodules were formed in high-density cultures but not in low-density cultures. Endogenous interleukin-6 (IL-6) production was found to be significantly lower in high-density cultures, which may partly explain the impaired osteoclast formation in high-density cocultures. Addition of IL-6 to the high-density cocultures indeed restored osteoclast formation. There appeared to be no overt difference in IL-6 receptor mRNA expression between high-density and low-density cultures. In conclusion, this paper suggests that mature, highly differentiated osteoblasts are not directly involved in osteoclastogenesis. In contrast, osteoblast-like cells lacking mature osteoblast markers induce osteoclast formation. Whether these low-density osteoblast-like cells represent an immature differentiation state or the lining cell phenotype is unclear.