甘精胰岛素联合赖脯胰岛素强化治疗2型糖尿病临床疗效和安全性观察

目的探讨甘精胰岛素联合赖脯胰岛素强化治疗2型糖尿病的临床疗效和安全性。方法选取确诊为2型糖尿病的患者120例作为研究对象,将患者按照随机数字表法分为对照组和观察组,每组60例,对照组采用诺和灵R联合诺和灵N进行治疗,观察组采用甘精胰岛素联合赖脯胰岛素进行治疗,比较两组患者的临床疗效和安全性。结果观察组患者治疗后的总有效率(90.00%)明显高于对照组(65.00%),观察组患者治疗后低血糖发生率(13.33%)明显低于对照组(41.67%),两组比较差异具有统计学意义(P0.05)。结论对2型糖尿病患者采用甘精胰岛素联合赖脯胰岛素进行强化治疗能够取得较好的临床效果,可以降低患者治疗后低血糖的发生率,值得在临床中推广应用。     

Better glycaemic control with BioChaperone glargine lispro co-formulation than with insulin lispro Mix25 or separate glargine and lispro administrations after a test meal in people with type 2 diabetes

Because of its physico-chemical properties, insulin glargine is usually not mixable with rapid insulins. BioChaperone BC147 is a polyanionic amphiphilic polymer, solubilizing insulin glargine at neutral pH, and thus enabling stable glargine formulation with fast-acting insulin lispro (BioChaperone glargine lispro co-formulation [BC Combo]). We investigated pharmacokinetic (PK) endpoints and postprandial glucose (PPG) control after administration of BC Combo (75% insulin glargine, 25% insulin lispro), insulin lispro Mix25 (LMix) and separate injections of insulins glargine (75% total dose) and lispro (25% total dose [G + L]) immediately before ingestion of a mixed meal in people with type 2 diabetes mellitus (T2DM), using a randomized, double-blind, double-dummy crossover study design. Participants received individualized bolus doses (mean 0.62 U/kg) of BC Combo, LMix or G + L, together with a solid mixed meal (610 kcal, 50% carbohydrate, 30% fat, 20% protein). Insulin dosages were kept constant for each study day. Thirty-nine participants with T2DM (mean ± SD age and glycated haemoglobin 60.8 ± 7.5 years and 64 ± 6 mmol/mol, respectively) were randomized. BC Combo improved the predefined primary endpoint, early PPG control, compared to LMix (incremental area under the blood glucose concentration–time curve from 0 to 2 hours after the meal [ΔAUC_BG,0–2h] reduction of 18%; P = 0.0009) and G + L (ΔAUC_BG,0–2h reduction of 10%; P = 0.0450). The number of mealtime hypoglycaemic episodes per participant was lower with BC Combo (22 episodes in 14 participants) compared to LMix (43 episodes in 20 participants; P = 0.0028), but not significantly different from G + L (28 episodes in 19 participants; P = 0.2523). BC Combo demonstrated superior early PPG control with fewer hypoglycaemic episodes compared to LMix and superior early PPG control compared to separate G + L administrations.     

Combination of oral antidiabetic agents with basal insulin versus premixed insulin alone in randomized elderly patients with type 2 diabetes mellitus

OBJECTIVES: To compare initiation of insulin therapy by adding once-daily insulin glargine to oral antidiabetic agents (OADs) with switching patients to premixed 30% regular, 70% human neutral protamine hagedorn insulin (70/30) without OADs. DESIGN: A 24-week, multicenter, open, randomized (1:1), parallel study. SETTING: Three hundred sixty-four poorly controlled patients with type 2 diabetes mellitus were treated with once-daily morning insulin glargine with continued OADs (glimepiride+metformin) (glargine+OAD) or twice-daily 70/30 alone. Insulin dosage in each group was titrated to target fasting blood glucose (FBG) of 100 mg/dL or less (or=6.7 mmol/L) and hemoglobin (Hb)A(1c) levels between 7.5% and 10.5% on OADs (glargine+OAD, n=67; 70/30, n=63). MEASUREMENTS: HbA(1c), FBG, hypoglycemia, insulin dose, and adverse events were recorded. RESULTS: HbA(1c) decreased from baseline to endpoint for both glargine+OAD (from 8.8% to 7.0%) and 70/30 (from 8.9% to 7.4%); adjusted mean HbA(1c) decrease for glargine+OAD and 70/30 was -1.9% and -1.4%, respectively (P=.003). More patients reached HbA(1c) of 7.0% or less without confirmed nocturnal hypoglycemia with glargine+OAD (n=37, 55.2%) than with 70/30 (n=19, 30.2%) (P=.006). FBG decreased significantly more with glargine+OAD (-57 mg/dL (-3.2 mmol/L)) than with 70/30 (-40 mg/dL (-2.2 mmol/L)) (P=.002). Patients treated with glargine+OAD experienced fewer episodes of any hypoglycemia (3.68/patient-year) than did those treated with 70/30 (9.09/patient-year) (P=.008). CONCLUSION: In elderly patients, addition of once-daily morning glargine+OAD is a simple regimen to initiate insulin therapy, restoring glycemic control more effectively and with less hypoglycemia than twice-daily 70/30 alone.     

Improving glycaemic control in patients with Type 2 diabetes mellitus without insulin therapy.

AIMS: In general practice at least 30% of those with Type 2 diabetes do not achieve good glycaemic control. We studied the effect of improving oral glucose-lowering medication in a primary care setting in patients treated with oral hypoglycaemic agents without satisfactory glycaemic control. METHODS: We provided flowcharts to general practitioners and outreach visits by trained facilitators, who checked adherence to the protocol. Fifty-two Dutch general practices with 2140 Type 2 diabetes mellitus (DM) patients recruited 288 patients < or = 75 years old inadequately controlled (HbA1c >7%) by diet or oral medication. Outcome measures were decrease of HbA1c, number of patients with HbA1c < or = 7%, and non-compliance rate. RESULTS: After a mean of 3.3 consultations over 14 weeks, 209 patients were following the protocol fully with a reduction in HbA1c from 8.7% to 6.7% (P<0.001). One hundred and fifty-eight patients (55%) achieved HbA1c < or =7%, and 51 (18%) persisted with HbA1c >7% unless fasting blood glucose < or =7 mmol/l (n=18) or a maximum of medication (n=33). Seventy-nine patients (27%) did not adhere to the protocol, mostly due to loss of motivation and non-attendance. CONCLUSIONS: A simple flowchart and relatively little support by trained facilitators results in improved glycaemic control.     

Better long-term glycaemic control with the basal insulin glargine as compared with NPH in patients with Type 1 diabetes mellitus given meal-time lispro insulin.

BACKGROUND: Glargine is a long-acting insulin analogue potentially more suitable than NPH insulin in intensive treatment of Type 1 diabetes mellitus (T1 DM), but no study has proven superiority. The aim of this study was to test superiority of glargine on long-term blood glucose (BG) as well as on responses to hypoglycaemia vs. NPH. METHODS: One hundred and twenty-one patients with T1 DM on intensive therapy on four times/day NPH and lispro insulin at each meal, were randomized to either continuation of NPH four times/day (n = 60), or once daily glargine at dinner-time (n = 61) for 1 year. Lispro insulin at meal-time was continued in both groups. In 11 patients from each group, responses to stepped hyperinsulinaemic-hypoglycaemia were measured before and after 1 year's treatment. RESULTS: Mean daily BG was lower with glargine [7.6 +/- 0.11 mmol/l (137 +/- 2 mg/dl)] vs. NPH [8.1 +/- 0.22 mmol/l (146 +/- 4 mg/dl)] (P < 0.05). HbA(1c) at 4 months did not change with NPH, but decreased with glargine (from 7.1 +/- 0.1 to 6.7 +/- 0.1%), and remained lower than NPH at 12 months (6.6 +/- 0.1%, P < 0.05 vs. NPH). Frequency of mild hypoglycaemia [self-assisted episodes, blood glucose < or = 4.0 mmol/l (72 mg/dl)] was lower with glargine vs. NPH (7.2 +/- 0.5 and 13.2 +/- 0.6 episodes/patient-month, P < 0.05). After 1 year, NPH treatment resulted in no change of responses to hypoglycaemia, whereas with glargine plasma glucose, thresholds and maximal responses of plasma adrenaline and symptoms to hypoglycaemia improved (P < 0.05). CONCLUSIONS: The simpler glargine regimen decreases the percentage of HbA(1c) and frequency of hypoglycaemia and improves responses to hypoglycaemia more than NPH. Thus, glargine appears more suitable than NPH as basal insulin for intensive treatment of T1 DM.     

Inequalities in glycaemic control in patients with Type 2 diabetes in primary care.

AIMS: To quantify relationships between patient and practice factors and glycaemic control in patients with Type 2 diabetes. METHODS: A cross-sectional study involving 1534 patients with Type 2 diabetes from 42 general practices in Nottingham, UK was undertaken. Patient characteristics were assessed by a clinical interview and case note review and practice characteristics by a questionnaire. The outcome measure was serum HbA(1c) concentration measured at entry to the study. Random effects linear regression was used to model patient and practice factors associated with glycaemic control. RESULTS: In multivariable regression analysis, HbA(1c) increased with increasing body mass index (BMI) [change in HbA(1c) for one unit increase in BMI: 0.03%, 95% confidence interval (CI) 0.01, 0.04], and was higher in those using oral medication (mean difference 0.75%, 95% CI 0.59, 0.92) or insulin compared with diet (mean difference 1.36%, 95% CI 1.10, 1.62). There was a dose-response relationship between HbA(1c) and increasing time since diagnosis. HbA(1c) was negatively associated with age (change per year -0.01%, 95% CI -0.02, -0.004). Patients registered at the most deprived practices had higher HbA(1c) values than those in the least deprived practices (mean difference 0.42%, 95% CI 0.14, 0.71), as did those in practices where annual reviews were carried out by the nurse alone (mean difference 0.24%, 95% CI 0.04, 0.44). CONCLUSIONS: Several patient and practice factors are related to glycaemic control. Poorer glycaemic control was associated with practice level deprivation and nurses undertaking annual reviews alone. Further research is required to explore outcomes of annual reviews undertaken by nurses alone. Greater resources may be needed by primary care teams working in deprived areas to address inequalities in diabetic control.     

First insulinization with basal insulin in patients with Type 2 diabetes in a real-world setting in Asia

Background: The First Basal Insulin Evaluation (FINE) Asia study is a multinational, prospective, observational study of insulin‐naïve Type 2 diabetes mellitus (T2DM) patients in Asia, uncontrolled (A1c ≥ 8%) on oral hypoglycemic agents, designed to evaluate the impact of basal insulin initiation. Methods: Basal insulin was initiated with or without concomitant oral therapy and doses were adjusted individually. All treatment choices, including the decision to initiate insulin, were at the physician’s discretion to reflect real‐life practice. Results: Patients (n = 2679) from 11 Asian countries were enrolled (mean [±SD] duration of diabetes 9.3 ± 6.5 years; weight 68.1 ± 12.7 kg; A1c 9.8 ± 1.6%). After 6 months of basal insulin (NPH insulin, insulin glargine, or insulin detemir), A1c decreased to 7.7 ± 1.4%; 33.7% patients reached A1c <7%. Fasting blood glucose (FBG) decreased from 11.7 ± 3.6 to 7.2 ± 2.5 mmol/L and 36.8% of patients reached FBG <6.1 mmol/L. The mean daily insulin dose prescribed increased marginally from 0.18 to 0.23 U/kg per day at baseline to 0.22–0.24 U/kg per day at Month 6. Mean changes in body weight and reported rates of hypoglycemia were low over the duration of the study. Conclusions: Initiation of insulin therapy is still being delayed by approximately 9 years, resulting in many Asian patients developing severe hyperglycemia. Initiating insulin treatment with basal insulin was effective and safe in Asian T2DM patients in a real‐world setting, but insulin needs may differ from those in Western countries.     

Preprandial vs. postprandial insulin lispro-a comparative crossover trial in patients with Type 1 diabetes.

AIMS: Administration of bolus insulin after eating may be a useful therapeutic option for some patients. This 6-month, crossover study compared metabolic effects of routine use of preprandial vs. postprandial injection of bolus insulin lispro. METHODS: Thirty-one patients with Type 1 diabetes injected insulin lispro either preprandially or postprandially for a 3-month period followed by the alternate regimen for a further 3 months. HbA1c, fructosamine and eight-point self-determined blood glucose profiles were measured and analysed using an anova model appropriate for a crossover design. RESULTS: Mean HbA1c decreased slightly from baseline with preprandial (-0.15 +/- 0.41%) and increased slightly with postprandial (0.11 +/- 0.48%) insulin lispro so that there was a significant (P = 0.008) difference between treatments in final HbA1c level. Mean fructosamine also decreased slightly with preprandial (-15 +/- 31 micro mol/l) but was almost unchanged (1 +/- 39 micro mol/l) with postprandial insulin lispro. Overall daily blood glucose was not different (P = 0.312) for preprandial compared with postprandial administration. However, mean preprandial glucose was lower (7.5 +/- 2.01 vs. 6.6 +/- 1.22 mmol/l; P = 0.026), whereas mean postprandial glucose was higher (7.7 +/- 1.8 vs. 8.7 +/- 2.1 mmol/l; P = 0.031) with postprandial insulin lispro administration. Mean blood glucose excursions were higher with postprandial compared with preprandial insulin lispro, indicating greater daily fluctuations. No difference in incidence of hypoglycaemia was observed with the two treatment regimens. CONCLUSIONS: Postprandial insulin lispro administration appeared to be an acceptable treatment regimen and may be of benefit in certain situations. However, the benefits of postprandial administration may have to be balanced against poorer glycaemic control with continuous long-term use.     

Troglitazone,an insulin action enhancer,improves glycaemic control and insulin sensitivity in elderly Type 2 diabetic patients

The management of Type 2 diabetes mellitus with currently available oral agents may be complicated in the elderly by an increased frequency of side-effects. The effects of troglitazone, an insulin action enhancer, were studied in elderly patients with Type 2 diabetes in a double-blind, parallel-group, placebo-controlled trial. A total of 229 patients (41 % male), mean age 75 (range 69–85) years, with two fasting capillary blood glucose values ≥7 and ≤15 mmol l⁻¹ (and within 4.0 mmol l⁻¹ of each other) and previously treated with either diet alone (30 %) or oral hypoglycaemic agents, were randomized to placebo or troglitazone 400 mg once daily or 200 mg twice daily, or 800 mg once daily or 400 mg twice daily, for 12 weeks. After 12 weeks’ treatment, fasting serum glucose was significantly lower in troglitazone-treated patients (troglitazone, adjusted geometric mean 9.4–10.4 mmol l⁻¹ vs placebo 12.7 mmol l⁻¹, p<0.001). Adjusted geometric mean fructosamine was also lower in troglitazone-treated patients by 5 to 15 % compared to placebo (P <0.05 at all doses except 400 mg od). There was no significant difference between troglitazone doses for improvement in glycaemic control. Troglitazone lowered adjusted geometric mean fasting plasma insulin by 27–34 % compared to placebo (P<0.001) and insulin sensitivity (HOMA-S) improved by 9–15 % in all troglitazone dose groups (p<0.001). Troglitazone also lowered serum non-esterified fatty acids and triglyceride. Adverse event incidence in troglitazone-treated patients was similar to that in patients treated with placebo. No weight gain or symptomatic hypoglycaemia was recorded at any of the doses studied. Troglitazone is effective and well tolerated in elderly patients with Type 2 diabetes mellitus, providing improved glycaemic control in the absence of weight gain. © 1998 John Wiley & Sons, Ltd.     

Effect of a pocket-size tablet-dispensing device on glycaemic control in Type 2 diabetic patients.

AIM: To evaluate whether a pocket-size tablet-dispensing device would improve adherence to therapy as judged by reduction of HbA(1c) levels in a large population of Type 2 diabetic patients. METHODS: The study design was prospective, randomized, open label with two parallel groups. Patients (2296) were recruited from general practitioners and internists and randomized to either receive a tablet dispenser (TD) or no intervention (control group, CO). Patients' characteristics and current oral therapy (including dosage) were recorded at baseline. HbA(1c) was compared between groups at baseline and after 6 months' intervention. RESULTS: Data were available in 2081 patients. Baseline characterisitcs, including age, body mass index (BMI), blood pressure and gender distribution were comparable between the two groups, as was HbA(1c)[7.9 (7.9-8.0), TD vs. 8.0 (7.9-8.0)%, CO, means (95% CI)]. After 6 months, HbA(1c) improved in both groups, but improvement was significantly greater in TD than in controls [-0.74 (0.67-0.80) vs. -0.53 (0.47-0.59)%, P < 0.0001]. Possession of a dispenser remained an independent predictor of improved control in a multiple regression model. In the subgroup analysis, the effect was significantly more pronounced (i) in patients receiving more medications and (ii) more diabetes medications per day (iii) in younger patients. CONCLUSION: In this large study population in a 'realistic' setting, a simple tablet-dispensing device led to a significant and clinically relevant improvement in HbA(1c) levels. Because patients with a more complex therapy regimen benefited more, we suggest that TD might have improved adherence to therapy.     

Twice-daily compared with once-daily insulin glargine in people with Type 1 diabetes using meal-time insulin aspart.

AIM: To compare blood glucose control when using insulin glargine twice daily at breakfast- and dinner-times with insulin glargine once daily at dinner time, in unselected people with Type 1 diabetes using insulin aspart at meal-times. METHODS: In this 8-week, two-way, cross-over study, 20 people with Type 1 diabetes were randomized to insulin glargine injection once daily at dinner-time or twice daily at breakfast- and dinner-times, both plus meal-time insulin aspart. Each 4-week treatment period concluded with a 24-h inpatient metabolic profile. RESULTS: Insulin doses, HbA1c, fructosamine concentration and pre-breakfast self-monitored blood glucose (SMBG) concentration did not differ between treatment periods. SMBG concentrations after breakfast, after lunch and before dinner were lower with twice-daily compared with once-daily dinner-time glargine [9.3 +/- 0.5 (+/- se) vs. 6.7 +/- 0.5 mmol/l, P = 0.003; 10.2 +/- 0.9 vs. 7.0 +/- 0.9 mmol/l, P = 0.024; 9.6 +/- 0.5 vs. 6.6 +/- 0.5 mmol/l, P = 0.001]. Mean 24-h SMBG concentration was lower with twice-daily glargine (7.1 +/- 0.5 vs. 8.8 +/- 0.5 mmol/l, P = 0.031). Within-day variability of SMBG concentration was lower with twice-daily glargine (sd 3.2 +/- 0.2 vs. 4.0 +/- 0.3 mmol/l, P = 0.044). Plasma free insulin concentration was higher in the afternoon with twice-daily glargine (21.9 +/- 1.4 vs. 16.1 +/- 1.3 mU/l, P = 0.009), but lower overnight (12.1 +/- 1.7 vs. 17.8 +/- 1.7 mU/l, P = 0.030), compared with once-daily injection. Plasma glucose concentration overnight was higher with twice-daily compared with once-daily glargine (mean 9.0 +/- 0.4 vs. 6.6 +/- 0.4 mmol/l, P = 0.001). CONCLUSIONS: Blood glucose concentration rises in the late afternoon in association with falling plasma insulin levels towards the end of the 24-h period after insulin glargine injection in some people with Type 1 diabetes using once-daily glargine at dinner-time plus a rapid-acting insulin analogue at meal-times. This is prevented by twice-daily injection of insulin glargine.     

Sustained effects of pioglitazone vs. glibenclamide on insulin sensitivity, glycaemic control, and lipid profiles in patients with Type 2 diabetes.

AIMS: This study compared the effects of 52 weeks' treatment with pioglitazone, a thiazolidinedione that reduces insulin resistance, and glibenclamide, on insulin sensitivity, glycaemic control, and lipids in patients with Type 2 diabetes. METHODS: Patients with Type 2 diabetes were randomized to receive either pioglitazone (initially 30 mg QD, n = 91) or micronized glibenclamide (initially 1.75 mg QD, n = 109) as monotherapy. Doses were titrated (to 45 mg for pioglitazone and 10.5 mg for glibenclamide) to achieve glycaemic targets during the next 12 weeks: fasting blood glucose of < or = 7 mmol/l and 1-h postprandial blood glucose of < or = 10 mmol/l. Patients were maintained on the titrated dose for 40 weeks. RESULTS: Pioglitazone significantly increased insulin sensitivity compared with glibenclamide, as assessed by homeostasis model assessment (17.0% vs. -13.0%; P < 0.001), quantitative insulin sensitivity check index (0.011 vs. -0.007; P < 0.001) and fasting serum insulin (-1.3 pmol/l vs. 23.8 pmol/l; P = 0.007). The glibenclamide group had significantly lower HbA1c than the pioglitazone group after 12 weeks of therapy (7.8% vs. 8.3%, P = 0.015), but significantly higher HbA1c after 52 weeks of therapy (7.8% vs. 7.2%, P = 0.001). Pioglitazone significantly (vs. glibenclamide) increased mean HDL-C (P < 0.001), decreased mean triglycerides (P = 0.019), and decreased mean atherogenic index of plasma (AIP; P = 0.001) and mean total cholesterol/HDL-C (P = 0.004), without significantly elevating mean total cholesterol or mean LDL-C compared with glibenclamide. CONCLUSIONS These data suggest that the effects of pioglitazone are more sustained than those of glibenclamide for improving insulin sensitivity in patients with Type 2 diabetes, and that 52 weeks' treatment with pioglitazone has favourable effects on glycaemic control and lipoprotein profile.     

Troglitazone in combination with sulphonylurea improves glycaemic control in Type 2 diabetic patients inadequately controlled by sulphonylurea therapy alone. Troglitazone Study Group.

AIM: The aim of this study was to investigate the effectiveness of troglitazone (a peroxisome proliferator-activated receptor-gamma agonist developed primarily for the treatment of Type 2 diabetes mellitus (DM)), 100 or 200mg/day, in terms of glycaemic control, lipid profile and tolerability, when given in addition to existing sulphonylurea therapy. METHODS: A 16-week, randomized, parallel-group placebo-controlled trial in 259 Type 2 diabetic patients already on sulphonylurea therapy. RESULTS: At week 16, adjusted geometric mean HbA1c with troglitazone 100mg (7.7%; P=0.023) and 200mg (7.4%; P<0.001) was lower with sulphonylurea alone (8.2%). At all weeks, adjusted geometric mean fasting serum glucose levels were lower in both troglitazone groups, compared with sulphonylurea alone (P=0.007 to P<0.001). At week 16, both troglitazone groups showed reductions in immune reactive insulin compared with sulphonylurea alone (200mg, 13%; P=0.032: 100mg, 5%; NS). Troglitazone reduced serum levels of nonesterified fatty acids at week 16 (100 g, 12%; P=0.042) and at all weeks (200mg, 17-24%; P=0.014 to P<0.001). The incidence of drug-related adverse events was similar in all groups (23-24% of patients). There was no apparent association between hypoglycaemia and the addition of troglitazone to sulphonylurea therapy. CONCLUSIONS: Troglitazone 100 or 200 mg added to usual sulphonylurea therapy in patients with Type 2 DM is associated with a significant improvement in glycaemic control, without altering the adverse-event profile of the sulphonylurea.