The effect of a diabetes education programme (PRIMAS) for people with type 1 diabetes: Results of a randomized trial

Objective

In a randomized, multi-centre trial, the efficacy of a self-management-oriented education programme (PRIMAS) for people with type 1 diabetes was compared with an established education programme as control group (CG). Primary outcome was the effect on glycaemic control in a 6-month follow-up. Secondary outcomes were the impact on emotional aspects, self-management related aspects and hypoglycaemia problems.

Methods

The study was conducted in an outpatient setting. 160 participants were randomized. Baseline characteristics in PRIMAS and CG were similar (age 45.1 ± 13.5 vs. 45.9 ± 13.1 years, p = .716; diabetes duration 18.8 ± 12.3 vs. 19.8 ± 13.4 years, p = .615; BMI 26.5 ± 4.6 vs. 27.5 ± 5.0 kg/m², p = .236; HbA1c 8.3 ± 1.1 vs. 8.1 ± 1.0%, p = .236).

Results

At follow-up there was a significant 0.4 percentage points greater reduction of HbA1c in PRIMAS compared to CG (Δ −0.4 ± 1.0% vs. Δ 0.0 ± 0.6%; p = .012). Also, diabetes-related distress (Δ −0.3 ± 0.7 vs. −0.1 ± 0.4, p = .032) and dissatisfaction with diabetes treatment (Δ −3.3 ± 6.9 vs. −1.9 ± 5.6, p = .024) decreased more in PRIMAS. Diabetes empowerment (Δ 2.6 ± 5.9 vs. 0.8 ± 5.1, p = .037) and diabetes self-efficacy (Δ 1.4 ± 3.6 vs. 0.2 ± 4.0, p = .013) increased in PRIMAS. Incidence of severe hypoglycemia, hypoglycemia awareness, diabetes knowledge, and self-care behaviour improved in both groups with no significant differences between groups.

Conclusion

PRIMAS is more effective in lowering HbA1c than a previously established education programmes and also showed superiority in reducing diabetes-related distress and increasing diabetes empowerment, diabetes self-efficacy and satisfaction with insulin therapy.     

Reversal of insulin resistance in type 1 diabetes following initiation of insulin treatment

The biological action and pharmacokinetics of insulin were assessed in nine type 1 (insulin-dependent) diabetic patients before and after 3 months conventional insulin treatment, and in seven age and weight-matched non-diabetic controls, by means of the euglycaemic insulin clamp technique. The mean (+/- S.E.) metabolic clearance rate of insulin, when infused at 1 mU/kg/min, was similar in untreated and treated diabetic patients and in controls (22.7 +/- 2.0, 19.3 +/- 3.8, and 22.9 +/- 3.3 ml/kg/min) but, when infused at 6 mU/kg/min, was greater (p less than 0.01 and less than 0.01) in untreated patients (18.0 +/- 2.5 ml/kg/min) than in treated patients (11.5 +/- 1.4 ml/kg/min) and controls (12.7 +/- 1.3 ml/kg/min). Insulin-mediated glucose disposal was reduced (p less than 0.01 and less than 0.01) at insulin infusion rates 1 and 6 mU/kg/min in untreated patients (18.5 +/- 1.9 and 33.8 +/- 4.5 mumol/kg/min) when compared with controls (35.8 +/- 3.4 and 62.0 +/- 4.7 mumol/kg/min) and was improved (p less than 0.01 and less than 0.01) following insulin treatment (36.1 +/- 4.6 and 64.8 +/- 4.2 mumol/kg/min). Daily insulin requirement fell by 33% following 3 months insulin treatment with improvement in mean HbA1 from 16.3 +/- 0.7 to 8.2 +/- 0.4%, but without significant increase in endogenous insulin secretion. The 'honeymoon phenomenon', which has traditionally been attributed exclusively to resurrection of endogenous insulin release, may also be related to normalization of insulin action following institution of insulin treatment.     

Use of the short-acting insulin analogue lispro in intensive treatment of Type 1 diabetes mellitus: importance of appropriate replacement of basal insulin and time-interval injection-meal

To establish whether lispro may be a suitable short-acting insulin preparation for meals in intensive treatment of Type 1 diabetes mellitus (DM) in patients already in chronic good glycaemic control with conventional insulins, 69 patients on intensive therapy (4 daily s.c. insulin injections, soluble at each meal, NPH at bedtime, HbA_1c <7.5 %) were studied with an open, cross-over design for two periods of 3 months each (lispro or soluble). The % HbA_1c and frequency of hypoglycaemia were assessed under four different conditions (Groups I–IV). Lispro was always injected at mealtime, soluble 10–40 min prior to meals (with the exception of Group IV). Bedtime NPH was continued with both treatments. When lispro replaced soluble with no increase in number of daily NPH injections (Group I, n = 15), HbA_1c was no different (p = NS), but frequency of hypoglycaemia was greater (p < 0.05). When NPH was given 3–4 times daily, lispro (Group II, n = 18), but not soluble (Group III, n = 12) decreased HbA_1c by 0.35 ± 0.25 % with no increase in hypoglycaemia. When soluble was injected at mealtimes, HbA_1c increased by 0.18 ± 0.15% and hypoglycaemia was more frequent than when soluble was injected 10–40 min prior to meals (Group IV, n = 24) (p < 0.05). It is concluded that in intensive management of Type 1 DM, lispro is superior to soluble in terms of reduction of % HbA_1c and frequency of hypoglycaemia, especially for those patients who do not use a time interval between insulin injection and meal. However, these goals cannot be achieved without optimization of basal insulin. © 1998 John Wiley & Sons, Ltd.     

达格列净联合短期胰岛素强化治疗对初治2型糖尿病患者代谢指标的影响

目的探讨新诊断2型糖尿病（T2DM）患者在短期胰岛素强化治疗的基础上联用达格列净对代谢指标的影响。 方法入选2018年5月至2020年8月于东莞东华医院内分泌科住院的新诊断T2DM患者60例,随机分为试验组（短期胰岛素强化+达格列净）和对照组（短期胰岛素强化）,收集治疗前（d0）、血糖达标后14天（D14）及停药后随访第12周（W12）的资料,分析两组患者的代谢指标的变化。 结果两组患者的体重、体质量指数（BMI）及腰围在W12时仍出现明显下降,且试验组下降更显著;试验组的血尿酸（UA）在D14出现明显下降,但停药后明显回升,而对照组的UA治疗前后无明显变化;两组患者的甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）在治疗后均出现明显下降,试验组高密度脂蛋白胆固醇（HDL-C）在停药后明显升高,而对照组治疗前后无明显变化。 结论对于新诊断的T2DM患者,在早期胰岛素强化降糖的同时加用达格列净治疗,可更显著减少体重、BMI、腰围,改善患者HDL-C等代谢指标。     

不同治疗方案对初诊2型糖尿病患者短期胰岛素强化治疗后长期缓解的影响

目的探讨不同治疗方案对初诊2型糖尿病患者短期胰岛素强化治疗后长期缓解的影响。方法84例新诊断的2型糖尿病患者，经过2周的胰岛素强化治疗后，随机分为两组，一组仅予饮食及运动治疗（SDE组），另一组在饮食及运动治疗的基础上加用二甲双胍（MET组），追踪观察至少1年时间，了解两种治疗方案在诱导糖尿病病情缓解作用方面的可能差异。结果（1）随访1年时，SDE组的缓解率为38．1％（16／42），显著低于MET组（缓解率为66．7％，P〈0．01。（2）在1年随访结束时，SDE缓解组中空腹血糖、糖化血红蛋白、曲线下血糖面积（AUCg）、稳态模型胰岛素抵抗指数（HOMA—IR）均高于MET缓解组，曲线下胰岛素面积（AUCi）、▲I30／▲G30以及HOMA—IR、▲I30／▲G30、AUCg、AUCi、BMI的各自变化值（1年随访结束时值-强化治疗结束时值）均低于MET缓解组，差异有统计学意义（P〈0．05—0．01）。结论短期胰岛素强化治疗可使相当多的病例获长期缓解，胰岛素强化治疗后应用二甲双胍治疗可能会增加长期缓解机会。     

Type 1 diabetes developed in a type 2 diabetic patient with severe insulin resistance

We report a 38-year-old female with severe insulin resistance who developed type 1 diabetes after being diagnosed with type 2 diabetes. At the initial examination, BMI was 31.8 kg/m² and HbA1c 10.8%. Her insulin secretion was sufficient (urinary CPR 80 μg/day) and the GAD antibody was negative. Following treatment with insulin and glimepiride, HbA1c decreased to 6.3%, though diabetic control deteriorated after 1 year (HbA1c, 11.0%) and her body weight was reduced in a short period, from 78 to 67 kg. Re-examination revealed that the GAD antibody was high (1870 U/mL, normal <1.5) and the anti-islet cell antibody positive, and insulin secretion decreased (urinary CPR 18 μg/day). Further, a hyperinsulinemic–euglycemic cramp study using an artificial pancreas showed that the patient had severe insulin resistance [glucose infusion rate 1.8 mg/(min kg); normal, 7.4 ± 2.4 (mean ± S.D.)]. An HLA-analysis showed that she was a homozygote of haplotype DRB1*0901-DQB1*0303. In spite of strict insulin therapy, glucose control was not improved. Pioglitazone could not be used because of side effects, however, metformin was effective for glucose control. The accumulation of case reports of patients with type 1 diabetes and insulin resistance is important for studying the relationship between the onset of the disease and insulin resistance, and for developing an effective treatment strategy.     

Comparison of insulin detemir and insulin glargine in subjects with Type 1 diabetes using intensive insulin therapy.

AIMS: To compare glycaemic control and risk of hypoglycaemia of twice-daily insulin detemir with once-daily insulin glargine in subjects with Type 1 diabetes. METHODS: In this 26-week, multicentre, open-label, parallel-group trial, 320 subjects with Type 1 diabetes received either insulin detemir twice daily or insulin glargine once daily. each in combination with premeal insulin aspart. RESULTS: After 26 weeks, HbA(1c) had decreased from 8.8 to 8.2% in the insulin detemir group and from 8.7 to 8.2% in the insulin glargine group. Home-measured fasting plasma glucose (PG) was lower with insulin glargine than with insulin detemir (7.0 vs. 7.7 mmol/l, P < 0.001). The overall shape of the home-measured nine-point PG profiles was comparable between treatments (P = 0.125). Overall, there was no significant difference in within-subject variation in PG (P = 0.437). Within-subject variation in predinner PG was lower with insulin detemir than with insulin glargine (P < 0.05). The overall risk of hypoglycaemia was similar with no differences in confirmed hypoglycaemia. However, the risk of severe and nocturnal hypoglycaemia was 72% and 32%, respectively, lower with insulin detemir than with insulin glargine (P < 0.05). Body weight gain was not significantly different comparing insulin detemir and insulin glargine (0.52 kg vs. 0.96 kg, P = 0.193). CONCLUSIONS: Treatment with twice-daily insulin detemir or once-daily insulin glargine, each in combination with insulin aspart, resulted in similar glycaemic control. The overall risk of hypoglycaemia was comparable, whereas the risks of both severe and nocturnal hypoglycaemia were significantly lower with insulin detemir.     

2型糖尿病患者胰岛素强化治疗的剂量及其相关因素分析

目的观察胰岛素强化治疗2型糖尿病患者达到满意血糖水平所用剂量及相关因素。方法收集1025例患者胰岛素用量,测定各临床指标以分析胰岛素剂量的相关因素。结果平均胰岛素总量39.30U/d,单位体重胰岛素量0.61U/kg;基础中效胰岛素量9.79U/d,占总胰岛素量的25.24%,餐前常规胰岛素量29.51U/d,占总胰岛素量的74.76%。根据单位体重胰岛素量将患者分成小剂量组和大剂量组,两组患者的病程、BMI、HbA1c、既往最大体重差异均有统计学意义。相关性分析显示单位体重胰岛素量与病程、HbA1c、出院时FPG及LDL-C呈正相关,与BMI、空腹和餐后C肽、既往最大体重以及HDL-C呈负相关。结论血糖达到满意控制的胰岛素总量为39.30U/d,其中基础中效胰岛素量占25%,餐前常规胰岛素量占75%,胰岛素剂量与病程、HbA1c呈正相关,与BMI、既往最大体重呈负相关。     

Sustained initial remission induced by intensive insulin treatment in type I diabetes. Possible role of the genetic Background

Summary A remission defmed by the possibility of temporarily discontinuing insulin therapy while blood glucose remains normal is not infrequently observed after intensive insulin therapy in newly diagnosed acute type I diabetes in the South of France. In order to analyze possible factors of such a remission, 47 newly diagnosed ketotic diabetics under 35 years of age of Caucasian origin were enrolled in a prospective study. They were given continuous s.c. insulin infusion for two weeks and oral agents were introduced on day 8. In 16 patients insulin could not be withdrawn. In 31 insulin was stopped for more than 3 months (mean 12.3, range 3.35) while blood glucose remained below 6 mmol/l fasting (mean 5.3) and 7.8 post-prandial (mean 5.1) and glycosylated Hb below 8.5% (mean 6). At presentation, diabetics who later went into remission and those who did not, showed no difference in age (22.3vs 23.1 years), sex ratio, apparent duration of symptoms (1.4vs 1.6 months), glycosylated hemoglobin (12.0vs 13.1%) and basal or post-prandial C-peptide values or presence of islet cell antibodies. No differences were observed in the frequency of DR3 and DR4 antigens in the two groups but diabetics who developed a remission bore the A 19.2 antigen (9/31vs 1/16) and the B18 one (11/31vs 1/16) more frequently, A 19.2 and B18 being associated in 7 cases of this group. This increased frequency in the remission group of HLA antigens, more often observed in diabetics of Mediterranean origin, suggests that differences in the genetic background may be associated with a difference in the evolution of the disease.     

Beneficial effects of flexible insulin therapy in children and adolescents with type 1 diabetes mellitus

Abstract. The purpose of this study was to determine the feasibility of a flexible multiple daily insulin (FMDI) regimen in routine pediatric diabetes care by comparing HbA_1c, body mass index (BMI), and episodes of severe hypoglycemia (SH) before and after initiation of FMDI therapy. Data from 44 patients (2–16 years old), on a conventional insulin (CI) regimen, were collected during quarterly diabetes clinic visits. These patients were transitioned from CI to FMDI regimen: pre-meal lispro (bolus) and once or twice daily Humulin Ultralente with or without bedtime Humulin NPH as the basal insulin. There was a significant improvement in HbA_1c in prepubertal (9.3%±1.3% vs. 8.0%±1.1%, p<0.002) and pubertal subjects (9.2%±1.0% vs. 8.2%±0.9%, p<0.001). Pubertal subgroup demonstrated an increase in BMI (21.3±3.1 vs. 22.7±3.2 kg/m², p<0.0001) after one year. The rate of SH was decreased in both prepubertal (p<0.01) and pubertal (p<0.05) groups of patients on FMDI therapy. The use of FMDI in a general pediatric diabetic population is a feasible therapeutic option for maintenance and possible improvement of glycemic control. It may effectively decrease the HbA_1c, and reduce hypoglycemic episodes, without producing an abnormal increase in BMI.     

Current status of insulin degludec in type 1 and type 2 diabetes based on randomized and observational trials

Insulin degludec is a new ultra-long-action basal insulin. Using treat-to-target protocols, controlled trials have shown comparable HbA_1c reductions with insulin degludec and comparators in both type 1 and type 2 diabetes. Most studies identify, however, better control of fasting plasma glucose with insulin degludec vs. either insulin glargine U100 or detemir, and all have consistently demonstrated clinically relevant decreases in (nocturnal) hypoglycaemic episodes. These characteristics have provided added therapeutic value for insulin degludec in clinical practice. Thus, the aim of this review is to discuss, within the context of randomized and observational studies, the clinical effects of insulin degludec use in type 1 and type 2 diabetes.     

Improved glycaemic control with insulin glargine plus insulin lispro: a multicentre, randomized, cross-over trial in people with Type 1 diabetes.

AIMS: To compare blood glucose control using insulin glargine + insulin lispro with that on NPH insulin + unmodified human insulin in adults with Type 1 diabetes managed with a multiple injection regimen. METHODS: In this 32-week, five-centre, two-way cross-over study, people with Type 1 diabetes (n = 56, baseline HbA1c 8.0 +/- 0.8%) were randomized to evening insulin glargine + mealtime insulin lispro or to NPH insulin (once- or twice-daily) + mealtime unmodified human insulin. Each 16-week period concluded with a 24-h inpatient plasma glucose profile. RESULTS: HbA1c was lower with glargine + lispro than with NPH + human insulin [7.5 vs. 8.0%, difference -0.5 (95% CI -0.7, -0.3) %, P < 0.001]. This was confirmed by an 8% lower 24-h plasma glucose area under the curve (AUC) (187 vs. 203 mmol l(-1) h(-1), P = 0.037), a 24% reduction in plasma glucose AUC > 7.0 mmol/l1 (47 vs. 62 mmol l(-1) h(-1), P = 0.017) and a 15% lower post-prandial plasma glucose AUC (75 vs. 88 mmol l(-1) h(-1), P = 0.002). There was no reduction in night-time plasma glucose AUC or increase in plasma glucose area < 3.5 mmol/l. Monthly rate of nocturnal hypoglycaemia was reduced by 44% with glargine + lispro (0.66 vs. 1.18 episodes/month, P < 0.001). CONCLUSIONS: Compared with NPH insulin + unmodified human insulin, the combination of insulin glargine with a rapid-acting insulin analogue as multiple-injection therapy for Type 1 diabetes improves overall glycaemic control as assessed by HbA1c and 24-h plasma glucose monitoring to a clinically significant degree, together with a reduction in nocturnal hypoglycaemia.     

胰岛素泵治疗儿童1型糖尿病疗效观察

目的 观察胰岛素泵持续皮下输注短效胰岛素(CSII)对儿童1型糖尿病(T1DM)的治疗效果。方法 ①胰岛素泵持续皮下输注CSII治疗6例传统胰岛素治疗(CIT)血糖控制不满意的TDM患儿。并比较其用泵前后空腹血糖(FBG)、餐后2小时血糖(2hPBG)、糖化血红蛋白(HbAk)、胰岛素(INS)用量、胆固醇(CH)及甘油三酯(FG)的变化；②治疗组用泵后上述代谢指标与33例正常对照组比较。结果 ①治疗组用泵后FBG、2hPBG、HbAk、INS用量、TG均较用泵前显著降低；用泵后INS用量减少16％；用泵后患儿依从性增高。②治疗组用泵后FBG、CH及TG均较正常对照组无差异，2hPBG、HbAk仍显著高于正常对照，但均达到强化治疗目的。结论 ①CSII治疗儿童TDM可显著改善其代谢指标，使血糖和血脂降至正常和接近正常。②CSII治疗儿童通过改善HbAk及血脂TDM，可延缓其慢性并发症的发生。     

短期胰岛素强化治疗对初诊2型糖尿病患者胰岛素抵抗及血尿酸的影响

目的 探讨短期胰岛素强化治疗对初诊2型糖尿病患者胰岛素抵抗及血尿酸的影响.方法 对36例初诊2型糖尿病患者进行为期2周的胰岛素强化治疗,比较治疗前后血尿酸（UA）、空腹血糖（FPG）及餐后2h血糖（2hPG）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）、胰岛素抵抗指数、胰岛素敏感指数.结果 经胰岛素强化治疗后,患者UA、FPG、2hPG、HbA1c、胰岛素抵抗指数均较治疗前明显下降（P均＜0.01）,胰岛素敏感指数明显升高（P＜0.01）.结论 短期胰岛素强化治疗可显著改善初诊2型糖尿病患者的胰岛素抵抗,降低血UA水平.     

Recent advances in treatment of youth with Type 1 diabetes: better care through technology.

While treatment of Type 1 diabetes mellitus (T1DM) in children and adolescents is especially difficult, recent technological advances have provided new therapeutic options to clinicians and patients. The urgency to achieve strict diabetes control and the introduction of new and improved insulin pumps have been accompanied by a marked increase in use of continuous subcutaneous insulin infusion (CSII) therapy in youth with diabetes. Results of clinical outcome studies indicate that CSII provides a safe and effective alternative to multiple daily injection (MDI) therapy, even when employed in a regular clinic setting in a large number of children. The safety and efficacy of CSII is further enhanced by the introduction of lispro and aspart insulin. The sharper peaks and shorter duration of action of these very rapid-acting insulin analogues provides a means to achieve better control of post-prandial hyperglycaemia with less late post-prandial and nocturnal hypoglycaemia. Glargine insulin, a soluble and essentially peakless long-acting insulin analogue, may provide a better basal insulin for MDI regimens, but there are limited published data with this agent in children with T1DM. A number of systems for pulmonary delivery of insulin are in development and preliminary results of Phase III studies have been promising. Like CSII, inhaled insulin allows the child to take bolus insulin doses before each meal without having to take a premeal injection. A major obstacle to effective treatment is that self-monitoring of three to four blood glucose levels a day often misses the marked glycaemic excursions that characterize T1DM in young patients. On the other hand, new continuous glucose sensing systems provide a wealth of data that can be used to optimize basal and bolus therapy, regardless of how insulin is administered. Even more important, we may finally be at the threshold of development of a practically applicable artificial pancreas.     

Severe localized lipoatrophy related to therapy with insulin analogs in type 1a diabetes mellitus

Insulin analog-related lipoatrophy is a rare complication of this type of treatment. We report a case of severe localized lipoatrophy in different locations in a patient with type 1a diabetes mellitus associated with other autoimmune disease.