Effect of pregnancy on the pharmacokinetics of metformin.

AIMS: To determine the effects of pregnancy on metformin pharmacokinetics. METHODS: Seven women with Type 2 diabetes mellitus taking metformin throughout pregnancy were studied on two occasions, once at 28-36 weeks gestation and once at least 8 weeks postpartum. Serum metformin concentrations were determined across a dosing interval using high-performance liquid chromatography. The areas under the serum concentration-time curve from 0 to 4 h post-dose (AUC0-4) and 0 to 8 h post-dose (AUC0-8) where possible, were compared in the pregnant and non-pregnant state. RESULTS: Metformin concentrations were lower in pregnancy in six subjects, with a mean (95% CI) AUC0-4 that was 69% (53.6, 84.8) of the postpartum value. The AUC0-4 of one subject was higher in pregnancy at 142% of the postpartum value. Overall, the mean (95% CI) AUC0-4 during pregnancy for all seven subjects was 80% (51.3, 107.8) of the postpartum value (P = 0.053, two-tailed t-test; P = 0.027, one-tailed t-test). CONCLUSION: These results are consistent with our hypothesis that the clearance of metformin increases in pregnancy as a result of enhanced renal elimination. A larger study is required to establish whether metformin dose adjustments are required in late pregnancy to maintain therapeutic effect.     

强化胰岛素治疗的2型糖尿病患者胰岛素脱离与否相关因素分析

目的比较强化胰岛素治疗的2型糖尿病患者在脱离胰岛素治疗和继续胰岛素治疗时的临床特点,分析脱离胰岛素的相关因素。方法统计66例入院的2型糖尿病患者的患病时间,检测开始胰岛素强化治疗、治疗过程、治疗结束时的糖化血红蛋白(HbA1 c)、体重指数(BM I)、胰岛素用量,观察脱离胰岛素所需时间。结果34例患者脱离胰岛素治疗,32例继续治疗,两组患者在年龄、治疗开始时间、BM I、HbA1 c差异均无统计学意义,而患病时间比较差异有统计学意义(P<0.05),脱离时的胰岛素用量和HbA1 c比继续治疗患者显著减低(P<0.01)。结论患病时间长短是胰岛素脱离与否的重要因素,胰岛素投入量及HbA1 c数值对脱离胰岛素与否有积极作用。     

Periodontal conditions in insulin-dependent diabetes mellitus.

In the present investigation, the frequency and severity of periodontal disease was assessed in a group of 71 patients with a mean duration of 16.5 years of insulin-dependent diabetes mellitus (IDD). The diabetics, aged 17-63 years, were under treatment at the diabetic outpatient clinic of the III Department of Medicine, University Central Hospital of Helsinki and at two clinics of the Helsinki Health Centre. Based upon their long-term medical records, 44 individuals were assessed to have a poorly controlled insulin-dependent diabetes mellitus (PIDD). At baseline of the present study, the PIDD group had a mean blood glucose level of 11.8 mmol/l and a mean glycosylated hemoglobin (HBA1) level of 10.7%. 27 subjects were classified as having a controlled insulin-dependent diabetes mellitus (CIDD). For each individual, site-specific recordings were made for the plaque index, gingival index, pocket depth, loss of attachment, bleeding after probing, gingival recession and radiographic loss of alveolar bone. Under similar plaque conditions, adult subjects with a long-term PIDD were found to have lost more approximal attachment and bone than subjects with a CIDD (P = 0.046, P = 0.019). These differences were not equally obvious when the subjects were classified according to the history of medical complications, such as retinopathies, neuropathies and nephropathies.     

Increased response of renal perfusion to the antioxidant vitamin C in type 2 diabetes.

BACKGROUND: Reactive oxygen species play a major role in the development of endothelial dysfunction. It is as yet unspecified whether increased oxidative stress contributes to endothelial dysfunction of the renal vasculature in patients with type 2 diabetes. METHODS: Renal haemodynamics were studied in 20 patients with type 2 diabetes and arterial hypertension (age 62 +/- 5 years) and 20 non-diabetic hypertensive patients at baseline and following infusions of the nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg); the substrate of nitric oxide synthase, L-arginine (100 mg/kg); and the antioxidant, vitamin C (3 g, co-infused with L-arginine 100 mg/kg). RESULTS: The response of renal plasma flow (RPF) to L-NMMA (-54 +/- 62 and -45 +/- 42 ml/min/1.73 m(2); P = NS) and L-arginine (+46 +/- 36 and +49 +/- 25 ml/min/1.73 m(2); P = NS) was not different between diabetic and non-diabetic patients. In contrast, vitamin C induced a more pronounced increase in RPF in diabetic than in non-diabetic patients when co-infused with L-arginine (+71+/-47 and +43+/-33 ml/min/1.73 m(2); P<0.05). CONCLUSIONS: The difference in the response of renal perfusion to an antioxidant suggests increased formation of reactive oxygen species and thereby reduced nitric oxide bioavailability in the renal vasculature of patients with type 2 diabetes.     

高果糖诱导IR大鼠模型血清脂质代谢的改变及意义

目的: 评估高果糖膳食对机体胰岛素敏感性及血清脂质代谢的影响及意义.方法:以高果糖膳食(果糖占总热量34.5%)诱导并经钳夹技术证实建立胰岛素抵抗(IR)大鼠模型,生化比色法测定血清游离脂肪酸(FFA),生化酶法测定血清甘油三酯(TG)及总胆固醇(TC).结果:高果糖膳食喂养4周后,实验组大鼠葡萄糖输注率由(11.5±0.6)mg/kg·min-1下降至(6.6±0.4)mg/kg·min-1(P<0.01);血清FFA由(0.45±0.09)mmol/L增至(0.78±0.19)mmol/L(P<0.01);TG由(0.54±0.10)mmol/L增至(0.96±0.22)mmol/L(P<0.01);TC由(1.96±0.32)mmol/L增至(2.42±0.21)mmol/L(P<0.01).结论:高果糖膳食可导致机体严重IR,是建立IR大鼠模型的有效手段;该模型同时伴有血清脂代谢各相关指标的明显异常,血脂的变化既是IR的结果,也是IR向纵深发展的原因和必要条件.     

Intravenous drug abuse and Type 1 diabetes: financial and healthcare implications.

AIMS: To determine the morbidity, mortality and healthcare costs of intravenous drug-abusing patients with Type 1 diabetes (IVDA-DM), who are admitted to hospital. METHODS: Retrospective case note analysis of admissions, complications and cost estimation over a 6-year period. Each drug-abusing patient (IVDA-DM) (n = 9) was compared with two controls (n = 18) with Type 1 diabetes but without a history of intravenous drug abuse (DM-controls). Admissions were also analysed for patients with intravenous drug abuse, but without Type 1 diabetes (IVDA-controls) (n = 198). Admissions were at a University teaching hospital in Liverpool, UK. DM-controls were drawn from a population attending diabetes outpatient clinics between 1997 and 2002 at the same hospital. The main outcome measures were: the duration and healthcare costs of hospital admissions per year, outpatient attendances per year, glycated haemoglobin (HbA(1c)), weight, micro- and macrovascular complications and mortality. RESULTS: Multiple admissions, mainly related to ketoacidosis, led to marked differences in mean (95% CI) inpatient days per year per patient [IVDA-DM 28.1 (13.6-42.7) vs. DM-control 1.1 (0.2-1.9); P < 0.0001], mean inpatient days per year per patient in critical care bed (IVDA-DM 1.7 (-0.7-4.2) vs. DM-control 0; P < 0.02) and mean costs of admission, per patient per year (pound sterling 7320 vs. pound sterling 230). The IVDA-DM group frequently omitted insulin, were underweight, failed to attend as outpatients and five had died by the end of 2002. The IVDA-controls spent considerably less time in hospital [3.4 (2.8-3.9) days per patient per year]. CONCLUSION: IVDA-DM patients have higher rates of diabetes complications, are admitted more frequently and have a high mortality compared with DM and IVDA-controls. The cost of inpatient care of this small group of patients was considerable.     

Effect of age and caloric restriction on insulin receptor binding and glucose transporter levels in aging rats

We report on the effect of age and chronic caloric restriction (CR) on insulin binding and glucose transporter content in both diaphragm and heart muscle membrane of young (11 months), mid-age (17 months), and old (29 month) ad libitum fed and CR Brown-Norway rats. The control animals received rat chow ad lib and CR animals were allowed 60% of ad libitum food. The CR regimen was initiated at four months of age and the animals were maintained on their respective diets until necropsy. There was no effect of age on insulin binding for either ad libitum or CR animals at each age evaluated. Caloric restriction significantly lowered insulin levels at each age studied when compared to the ad libitum-fed rats. However, CR animals were noted to have increased insulin binding (p < 0.001) compared to ad libitum-fed animals at each age for diaphragm muscle. For the heart, there appeared to be a decreased binding, particularly at higher insulin concentrations, in CR-fed animals. There was no net change in Glut-1 or Glut-4 levels for heart muscle membrane, or Glut-4 levels for diaphragm muscle membrane between ad libitum or CR animals. This data indicates that caloric restriction may have tissue-specific effects for insulin receptor binding, and that the improved insulin sensitivity in CR states is not a result of altered glucose transporter protein content.     

儿童糖尿病30例临床分析

30例儿童糖尿病患者年龄2～14岁,83.3％病前有感染史,起病多较急,年龄越小“三多一少”症状越不典型,多以酮症酸中毒昏迷就诊,其中20％被误诊。建议采用小剂量胰岛素静脉滴注治疗。     

Cross reactivity between IA-2 and phogrin/IA-2β in binding of autoantibodies in IDDM

Summary Patients with insulin-dependent diabetes mellitus (IDDM) possess antibodies to the cytoplasmic domains of two closely related tyrosine phosphatase-like proteins, IA-2 and phogrin, previously detected as 40 kDa and 37 kDa tryptic fragments, respectively. A higher proportion of IDDM patients possess antibodies to IA-2 than to phogrin, and autoimmunity to phogrin might arise through cross-reactivity with the highly homologous IA-2. In this study, we have investigated the major regions of IA-2 recognized by antibodies in IDDM patients and examined the ability of phogrin to block antibody binding to these regions as a measure of cross-reactivity. Analysis of antibody binding to in vitro transcribed and translated polypeptides representing different regions of the cytoplasmic domain of IA-2 identified five different patterns of reactivity with antibodies in IDDM. Protein footprinting analysis, whereby polypeptide fragments generated on protease treatment of immune complexes are studied, indicated considerable heterogeneity in antibody recognition of IA-2, even between sera with similar reactivity to deletion mutants. Blocking studies with recombinant phogrin indicated that IA-2 antibodies recognize epitopes that are both unique to IA-2 and shared with phogrin. The amino-terminal 150 amino acids of the cytoplasmic domain of IA-2 encompass epitopes that are not represented on phogrin, whereas shared epitopes are localized within the carboxy-terminal 220 amino acids. The results demonstrate considerable heterogeneity between IDDM patients in autoantibody recognition of IA-2 in IDDM, whereas antibody recognition of phogrin is restricted in most patients to epitopes also present on IA-2. [Diabetologia (1997) 40: 1327–1333] Received: 4 April 1997 and in revised form: 2 July 1997