Intensified insulin therapy and the risk of severe hypoglycaemia

Summary The objectives of the present analyses were to assess the association between HbA_{1 c} levels and severe hypoglycaemia (SH, treatment with glucose i. v. or glucagon injection) and to identify predictors of SH in a prospective multicentre trial. The study population consisted of 636 insulin-dependent diabetic patients who had participated in a structured 5-day in-patient group treatment and teaching programme for intensification of insulin therapy (ITTP) in one of 10 hospitals and who were re-examined after 1, 2, 3, and 6 years including assessment of demographic, disease and treatment related parameters, diabetes-related knowledge, behaviour, and emotional coping. At baseline, age (mean ± SD) was 27 ± 7 years, diabetes duration 9 ± 7 years and HbA_{1 c} 8.3 ± 1.9 %. During the 6-year follow-up, the mean HbA_{1 c} value improved to 7.6 %, and in patients with a diabetes duration of more than 1 year at entry into the study (n = 538) the incidence of SH decreased from 0.28 cases/patient/year during the year preceding the ITTP to 0.17 cases/patient/year. The patient group was divided into decile groups according to mean follow-up HbA_{1 c} values. In each group more than 230 patient years could be analysed. Groups with mean HbA_{1 c} values of 5.7, 7.0, 7.4, 7.7 and 8.9 % had comparable risks of SH (0.15–0.19 cases/patient/year). In a logistic regression analysis, mean HbA_{1 c} during follow-up, a history of SH during the year preceding the ITTP, C-peptide level, emotional coping, carrying emergency carbohydrates (as assessed at the 1-year follow-up), and age at onset of diabetes were significant independent predictors of SH. The incidence of SH between centres varied between 0.05 and 0.27 cases/patient/year. In conclusion, in the present analyses no linear or exponential relationship between HbA_{1 c} and severe hypoglycaemia could be identified by using simple group comparisons. Applying complex regression analyses, various patient-related predictors of severe hypoglycaemia were identified. [Diabetologia (1997) 40: 926–932] Received: 23 January 1997 and in revised form: 1 April 1997     

高效液相色谱法同时测定盐酸维拉帕米及其主要代谢产物

建立了反相高效液相色谱法同时测定人血浆中维拉帕米及其主要代谢产物去甲维拉帕米血药浓度.以甲醇—水—三乙胺(67∶33∶0.4,pH6.7)为流动相,乙吗噻嗪(ethmosine)为内标,样品用正己烷—正丁醇混合液提取浓缩后进样,紫外检测器检测(279nm)。此法操作简便,精密度好,日内、日间误差:维拉帕米<8.6%,去甲维拉帕米<7.6%;方法回收率高,维拉帕米、去甲维拉帕米回收率均>92%。两者血药浓度在25～1000ng·ml-1范围内呈线性关系,最小检测浓度维拉帕米:2.5ng·ml^-1,去甲维拉帕米:5.0ng·ml^-1。应用该法测定了6名志愿者口服盐酸维拉帕米片剂后的血药浓度。     

Lipopolysaccharide-Induced Bone Loss in Rodent Models: A Systematic Review and Meta-Analysis

Osteoporosis has traditionally been characterized by underlying endocrine mechanisms, though evidence indicates a role of inflammation in its pathophysiology. Lipopolysaccharide (LPS), a component of gram-negative bacteria that reside in the intestines, can be released into circulation and stimulate the immune system, upregulating bone resorption. Exogenous LPS is used in rodent models to study the effect of systemic inflammation on bone, and to date a variety of different doses, routes, and durations of LPS administration have been used. The study objective was to determine whether systemic administration of LPS induced inflammatory bone loss in rodent models. A systematic search of Medline and four other databases resulted in a total of 110 studies that met the inclusion criteria. Pooled standardized mean differences (SMDs) and corresponding 95% confidence intervals (CI) with a random-effects meta-analyses were used for bone volume fraction (BV/TV) and volumetric bone mineral density (vBMD). Heterogeneity was quantified using the I² statistic. Shorter-term (<2 weeks) and longer-term (>2 weeks) LPS interventions were analyzed separately because of intractable study design differences. BV/TV was significantly reduced in both shorter-term (SMD = −3.79%, 95% CI [−4.20, −3.38], I² 62%; p < 0.01) and longer-term (SMD = −1.50%, 95% CI [−2.00, −1.00], I² 78%; p < 0.01) studies. vBMD was also reduced in both shorter-term (SMD = −3.11%, 95% CI [−3.78, −2.44]; I² 72%; p < 0.01) and longer-term (SMD = −3.49%, 95% CI [−4.94, −2.04], I² 82%; p < 0.01) studies. In both groups, regardless of duration, LPS negatively impacted trabecular bone structure but not cortical bone structure, and an upregulation in bone resorption demonstrated by bone cell staining and serum biomarkers was reported. This suggests systemically delivered exogenous LPS in rodents is a viable model for studying inflammatory bone loss, particularly in trabecular bone. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).