Effects of 4 weeks’ administration of pramlintide, a human amylin analogue, on glycaemia control in patients with IDDM: effects on plasma glucose profiles and serum fructosamine concentrations

Summary The effects of 4 weeks' administration of pramlintide, an analogue of the human hormone amylin, on blood glucose control in 215 patients with insulin-dependent diabetes mellitus were examined in a 4-week, randomized, double-blind, placebo-controlled, parallel-group trial. Pramlintide was administered subcutaneously prior to meals in four dosing regimens: 30 μg four times per day (breakfast, lunch, dinner, and evening snack), 30 μg three times per day (breakfast, lunch and dinner [BLD]), 30 μg three times per day (breakfast, dinner and evening snack [BDS]), and 60 μg twice per day (breakfast and dinner). After 4 weeks of pramlintide 30 μg four times per day administration, there was a statistically significant reduction in the mean 24 h plasma glucose concentration when compared to placebo (– 1.4 ± 0.5 vs 0.3 ± 0.5 μmol/l, p = 0.009). Serum fructosamine concentrations were reduced 62 ± 10 μmol/l in the pramlintide 30 mg four times per day group, 43 ± 7 μmol/l in the pramlintide 30 μg three times per day (BLD) group, 47 ± 6 μmol/l in the pramlintide 30 μg three times per day (BDS) group, 46 ± 7 μmol/l in the pramlintide 60 μg twice per day group, and 29 ± 8 μmol/l by placebo. The incidence of hypoglycaemia was not different in any pramlintide group compared to the placebo group. Nausea, the most frequent adverse event, subsided after the first week of treatment in the majority of patients. In conclusion, pramlintide improved blood glucose control over a 4-week period without increased hypoglycaemia and was well tolerated. Future studies using a longer period of pramlintide administration with assessment of HbA_1c as the measurement of glycaemic control are warranted. [Diabetologia (1997) 40: 1278–1285] Received: 3 January 1997 and in revised form: 2 May 1997     

Failure to adequately adapt reduced insulin sensitivity with increased insulin secretion in women with impaired glucose tolerance

Summary To study the islet adaptation to reduced insulin sensitivity in normal and glucose intolerant post-menopausal women, we performed a euglycaemic, hyperinsulinaemic clamp in 108 randomly selected women, aged 58–59 years. Of the 20 women with the lowest insulin sensitivity, 11 had impaired glucose tolerance (IGT) whereas 9 had normal glucose tolerance (NGT). These women together with 15 women with medium insulin sensitivity and 16 women with high insulin sensitivity and NGT were further examined with arginine stimulation at three glucose levels (fasting, 14 and >25 mmol/l). In NGT, the acute insulin response (AIR) to 5 g i. v. arginine at all three glucose levels and the slope_AIR, i. e. the glucose potentiation of insulin secretion, were markedly increased in the women with the lowest insulin sensitivity and NGT compared to those with medium or high insulin sensitivity. In contrast, in low insulin sensitivity, AIR was significantly lower in IGT than in NGT (at glucose 14 mmol/l p=0.015, and at >25 mmol/l p=0.048). The potentiation of AIR induced by low insulin sensitivity in women with NGT was reduced by 74% (AIR at 14 mmol/l glucose) and 57% (AIR at >25 mmol/l glucose), respectively, in women with IGT. Also the slope_AIR was lower in IGT than in NGT (p=0.025); the increase in slope_AIR due to low insulin sensitivity was abolished in IGT. In contrast, glucagon secretion was not different between women with IGT as opposed to NGT. We conclude that as long as there is an adequate beta-cell adaptation to low insulin sensitivity with increased insulin secretory capacity and glucose potentiation of insulin secretion, NGT persists.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - AIR acute insulin response - AGR acute glucagon response     

Abnormal insulin secretion and glucose metabolism in pancreatic islets from the spontaneously diabetic GK rat

Summary Insulin secretion and islet glucose metabolism were compared in pancreatic islets isolated from GK/Wistar (GK) rats with spontaneous Type 2 (non-insulin-dependent) diabetes mellitus and control Wistar rats. Islet insulin content was 24.5±3.1 U/ng islet DNA in GK rats and 28.8±2.5 U/ng islet DNA in control rats, with a mean (±SEM) islet DNA content of 17.3±1.7 and 26.5±3.4 ng (p < 0.05), respectively. Basal insulin secretion at 3.3 mmol/l glucose was 0.19±0.03 · ng islet DNA^–1· h^–1 in GK rat islets and 0.40±0.07 in control islets. Glucose (16.7 mmol/l) stimulated insulin release in GK rat islets only two-fold while in control islets five-fold. Glucose utilization at 16.7 mmol/l glucose, as measured by the formation of ³H₂O from [5-³ H]glucose, was 2.4 times higher in GK rat islets (3.1±0.7 pmol · ng islet DNA^–1 · h^–1) than in control islets (1.3±0.1 pmol · ng islet DNA^–1 · h^–1; p<0.05). In contrast, glucose oxidation, estimated as the production of ¹⁴CO₂ from [U-¹⁴C]glucose, was similar in both types of islets and corresponded to 15±2 and 30±3 % (p<0.001) of total glucose phosphorylated in GK and control islets, respectively. Glucose cycling, i. e. the rate of dephosphorylation of the total amount of glucose phosphorylated, (determined as production of labelled glucose from islets incubated with ³H₂O) was 16.4±3.4% in GK rat and 6.4±1.0% in control islets, respectively (p<0.01). We conclude that insulin secretion stimulated by glucose is markedly impaired in GK rat islets. Glucose metabolism is also altered in GK rat islets, with diminished ratio between oxidation and utilization of glucose, and increased glucose cycling, suggesting links between impaired glucose-induced insulin release and abnormal glucose metabolism.     

The association of physical activity with obesity,fat distribution and glucose intolerance in Pima Indians

Summary The relationships between physical activity, obesity, fat distribution and glucose tolerance were examined in the Pima Indians who have the highest documented incidence of non-insulin-dependent diabetes. Fasting and 2-h post-load plasma glucose concentrations, body mass index, and waist-to-thigh circumference ratios were determined in 1054 subjects aged 15–59 years. Current (during the most recent calendar year) and historical (over a lifetime) leisure and occupational physical activity were determined by questionnaire. Current physical activity was inversely correlated with fasting and 2-h plasma glucose concentrations, body mass index and waist-to-thigh ratios for most sex-age groups even when diabetic subjects were excluded. Controlled for age, obesity and fat distribution, activity remained significantly associated with 2-h plasma glucose concentrations in males. In subjects aged 37–59 years, individuals with diabetes compared to those without reported significantly less leisure physical activity during the teenage years (median hours per week of activity, 9.1 vs 13.2 for men; 1.0 vs 2.2 for women). Controlled for body mass index, sex, age and waist-to-thigh ratio, subjects who reported low levels of historical leisure physical activity had a higher rate of diabetes than those who were more active. In conclusion, current physical activity was inversely related to glucose intolerance, obesity and central distribution of fat, particularly in males. Subjects with diabetes were currently less active and reported less historical physical activity than non-diabetic subjects. These findings suggest that activity may protect against the development of non-insulin-dependent diabetes both directly and through an influence on obesity and fat distribution.     

Associations of Left Ventricular Hypertrophy and Geometry with Adverse Outcomes in Patients with CKD and Hypertension

Background and objectives

Left ventricular hypertrophy (LVH) and abnormal left ventricular (LV) geometry predict adverse outcomes in the general and hypertensive populations, but findings in CKD are still inconclusive.

Design, setting, participants, & measurements

We enrolled 445 patients with hypertension and CKD stages 2–5 in two academic nephrology clinics in 1999–2003 who underwent both echocardiography and ambulatory BP monitoring. LVH (LV mass >100 g/m² [women] and >131 g/m² [men]) and relative wall thickness (RWT) were used to define LV geometry: no LVH and RWT≤0.45 (normal), no LVH and RWT>0.45 (remodeling), LVH and RWT≤0.45 (eccentric), and LVH and RWT>0.45 (concentric). We evaluated the prognostic role of LVH and LV geometry on cardiovascular (CV; composite of fatal and nonfatal events) and renal outcomes (composite of ESRD and all-cause death).

Results

Age was 64.1±13.8 years old; 19% had diabetes, and 22% had CV disease. eGFR was 39.9±20.2 ml/min per 1.73 m². LVH was detected in 249 patients (56.0%); of these, 125 had concentric LVH, and 124 had eccentric pattern, whereas 71 patients had concentric remodeling. Age, women, anemia, and nocturnal hypertension were independently associated with both concentric and eccentric LVH, whereas diabetes and history of CV disease associated with eccentric LVH only, and CKD stages 4 and 5 associated with concentric LVH only. During follow-up (median, 5.9 years; range, 0.04–15.3), 188 renal deaths (112 ESRD) and 103 CV events (61 fatal) occurred. Using multivariable Cox analysis, concentric and eccentric LVH was associated with higher risk of CV outcomes (hazard ratio [HR], 2.59; 95% confidence interval [95% CI], 1.39 to 4.84 and HR, 2.79; 95% CI, 1.47 to 5.26, respectively). Similarly, greater risk of renal end point was detected in concentric (HR, 2.33; 95% CI, 1.44 to 3.80) and eccentric (HR, 2.30; 95% CI, 1.42 to 3.74) LVH. Sensitivity analysis using LVH and RWT separately showed that LVH but not RWT was associated with higher cardiorenal risk.

Conclusions

In patients with CKD, LVH is a strong predictor of the risk of poor CV and renal outcomes independent from LV geometry.     

Long-term safety, efficacy and side-effects of continuous subcutaneous insulin infusion treatment for Type 1 (insulin-dependent) diabetes mellitus: a one centre experience

Summary A follow-up study of 116 Type 1 (insulin-dependent) diabetic patients on long-term continuous subcutaneous insulin infusion was conducted after 4.5±0.2 years. The average HbA_1c-value of these patients decreased by 1% to 6.7±0.1% during this observation period. Typical side effects of continuous subcutaneous insulin infusion such as skin inflammation at the catheter insertion site occurred with similar frequency as has been reported previously by other authors. Diabetic ketoacidosis (0.14 per patient year) and disabling hypoglycaemia (0.1 per patient year, including 0.05 hypoglycaemic coma per patient-year) occurred at substantially lower rates than in other comparable studies with Type 1 diabetic patients at a similar degree of metabolic control. Subgroup evaluation suggested that a normal (<5.6%) HbA_1c-value at follow-up was associated with increased incidence of disabling hypoglycaemia, whereas poor metabolic control (HbA_1c>7.5%) was associated with increased rates of skin complications and hospital treatment for ketoacidosis. Thus, under the policies of this diabetes centre, continuous subcutaneous insulin infusion has proved to be beneficial to a large proportion of experienced adult Type 1 diabetic patients, who voluntarily had opted for, and continued with, this particular mode of insulin treatment.     

不同血液净化模式对急性肾损伤患儿血清β2微球蛋白的清除效果及安全性研究

目的 探讨不同血液净化模式对急性肾损伤(acute kidney injury,AKI)患儿血清β2微球蛋白(β2-microglulin,β2-MG)的清除效果和安全性研究.方法 收集2011年3月至2013年3月收治于贵阳市儿童医院肾脏免疫科和儿童重症监护病房(PICU)行血液净化治疗98例次的小儿AKI的患者38例.其中男20例,女18例,年龄5个月～14岁.其中持续性肾脏替代治疗(continuous renal replacement therapy,CRRT) 66例次[包括连续性静-静脉血液透析(continuous veno-venous hemofiltration,CVVH)及连续性静-静脉血液透析滤过(continuous veno-venous hemodiafiltration,CVVHDF)],间歇性血液透析(intermittent hemodialysis,IHD) 32例次.原发性疾病:循环障碍7例,各种肾毒性药物及毒物中毒10例,脓毒症伴多器官衰竭9例,肾脏实质性疾病如肾病综合征、链球菌感染后肾小球肾、狼疮性肾炎、急进性肾炎等12例.依据不同血液净化方式分为CRRT组和IHD组,其中CRRT组上机治疗8 ～16h,IHD组治疗2.5～3h.评价患儿血尿素氮(blood urea nitrogen,BUN)、肌酐(serum creatinine,SCr)及水电解质酸碱平衡、β2-MG等.结果 AKI行血液净化治疗共38例98例次,其中CRRT组(包括CVVH、CVVHDF) 66例次,IHD组32例次.进展至终末期肾病需长期维持透析治疗2例(占5％),病死率0. (1) CRRT组治疗前后血BUN、Scr分别为[(22.34 ±2.08) mmol/L,(12.24 ±0.98) mmol/L]、[(310.23 ±85.34) μmol/L、(178.15 ±34.12) μmol/L],差异有统计学意义(t=12.39,t=5.906,P均＜0.05);IHD组冶疗前后血BUN、Scr分别为[(23.80±2.14) mmol/L,(7.39±0.88) mmol/L]、[(350.11±78.42) μmol/L,(108.20 ±28.20) μmol/L],差异有统计学意义(t =29.04,t=13.83,P均＜0.05);(2) CRRT组及IHD组β2-MG清除率分别为(40.50±7.20)％、(1.50±0.05)％,CRRT组β2-MG清除效果优于IHD组,差异有统计学意义(P＜0.05);(3) CRRT组中不良反应出现少,患儿安全性较IHD为高.结论 CRRT对小儿急性肾损伤具有清除血清β2-MG好、血流动力学稳定等特点,是治疗小儿急性肾损伤的一种快速、有效和安全的方法.     

规范化胰岛素注射培训对社区糖尿病患者血糖达标率的影响

目的 探讨规范化胰岛素注射培训对社区糖尿病患者血糖达标率的影响。 方法 选取某社区使用胰岛素笔注射治疗的糖尿病患者70例,通过调查问卷记录患者在胰岛素注射方面存在的问题,将患者随机分为培训组与对照组各35例,培训组根据所反映的问题采取规范化胰岛素注射培训,对照组采用传统的培训方式,2组均在培训后6个月进行效果评价。 结果 培训后培训组在胰岛素注射知识掌握及注射技巧方面优于对照组,血糖达标率高于对照组(χ²=4.644,P=0.031)。 结论 通过规范化胰岛素注射培训可提高社区糖尿病患者胰岛素注射知识及注射技巧掌握情况,提高患者血糖达标率。     

Importance of vancomycin loading doses in intermittent infusion regimens

Purpose

Delayed achievement of target vancomycin serum concentrations may adversely affect clinical outcomes. The objective of this retrospective study was to explore the real frequency of loading dose use and to evaluate the impact of loading dose for the achievement of vancomycin PK/PD target in adult patients treated with intermittent vancomycin. As a secondary aim we determined optimal vancomycin loading dose based on individual pharmacokinetic calculations.