Comparison of glycaemic control over 1 year with pioglitazone or gliclazide in patients with Type 2 diabetes.

AIMS: To compare long-term (1 year) efficacy and safety of pioglitazone and gliclazide in patients with Type 2 diabetes. METHODS: This was a double-blind, multicentre, comparative, parallel group trial in 283 patients with Type 2 diabetes, who were randomized to receive 1-year treatment with pioglitazone 30-45 mg/day or gliclazide 80-320 mg/day. Drug dose was titrated on the basis of self-monitored blood glucose (SMBG) measurements and HbA1c values. The 1-year changes in HbA1c, fasting blood glucose (FBG), insulin, HOMA-S (HOmeostatic Model Assessment) and SMBG were compared. In a subgroup of patients (n = 10), systemic glucose production and utilization were determined by a combination of isotopic (deuterated glucose) and clamp techniques. RESULTS: In both groups, there were similar decreases in HbA1c (pioglitazone: -0.79%; gliclazide: -0.79%) and FBG (pioglitazone: -1.0 mmol/l; gliclazide: -0.7 mmol/l), whereas the slope of the reduction of fasting blood glucose was different between groups (P = 0.004). Insulin levels as well as insulin resistance assessed using HOMA-S decreased significantly only after pioglitazone treatment (-11.94 pmol/l and -1.03, respectively, both P = 0.002 vs. baseline). A significantly greater reduction in systemic glucose production was observed in the pioglitazone group (-2.48 micromol/kg/min, P = 0.042) than in the gliclazide group (-1.02 micromol/kg/min). A few, mild adverse events occurred in both groups. CONCLUSIONS: A comparable decrease in HbA1c and FBG was observed with pioglitazone and gliclazide. However, with pioglitazone there was a continuous decrease in FBG over 1 year, whereas gliclazide failed to maintain a similar trend. This favourable effect of pioglitazone was due to its insulin-sensitizing effect and ability to decrease systemic glucose production.     

Acute onset and worsening of diabetes concurrent with administration of statins

We report a patient in whom the administration of HMG CoA reductase inhibitors (statins) might have triggered the onset and worsening of diabetes. The patient was a 48-year-old Japanese man who underwent annual medical examination but had never been told of hyperglycemia. Four months after the commencement of atorvastatin (10 mg/day) treatment, a diagnosis of diabetes mellitus was made from his typical symptoms of hyperglycemia, postprandial plasma glucose level of 29.8 mmol/l and HbA1c of 11.5%. After 2 months of insulin therapy and 3 months after the cessation of atorvastatin, almost complete resolution of diabetes was observed. During the subsequent 3 months, diet therapy alone was sufficient to control blood glucose level. Then, we prescribed pravastatin (20 mg/day). During the subsequent 3 months, HbA1c was gradually increased. However, after discontinuation of pravastatin, HbA1c was gradually decreased. In the general population, statin does not seem to have critical adverse effects on glucose tolerance, but it may uncommonly modify the natural course of the development of diabetes in certain patients.     

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.     

Insulin initiation in type 2 diabetic patients admitted in hospital in France and follow-up at 1 year

OBJECTIVES AND METHODS: The IDAHO 2 epidemiological survey was conducted in departments of diabetology in insulin-na?ve type 2 diabetics for whom insulin was initiated. The objective was to assess the patients' profile, the treatments proposed during hospital stay and after one year. RESULTS: 797 patients were analysed. Their characteristics were: age 64+/-12 years, 49% males, weight: 78+/-17 kg, BMI: 29+/-6 kg/m2, diabetes duration 11 years, prevalence of complications: 68%, fasting blood glucose 13+/-6 mmol/l, HbA1c: 10+/-2.2%; treatment prior to insulin comprised: at least 2 OHA: 71% of cases, one: 21%, no OAD: 8%. At hospital discharge, 54% of the patients used basal insulin. After 1 year, 670 continued on insulin. The insulin initiation was accompanied by a decrease in the FBG level (baseline: 13+/-6 mmol/l; final: 8.5+/-2.75 mmol/l; P<0.0001) and a HbA1c improvement (baseline: 10+/-2.2%; final: 7.9+/-1.4%; P<0.0001). This was observed du-ring the first 6 months (HbA1c: 7.8%, P<0.0001 versus baseline). 80% of the patients remained on the same insulin regimen after 1 year: 35% had 1 injection/day, 44% had 2, 12% had 3 and 9% had a complex regimen. The weight gain, the final daily dose and hypoglycaemias increased with the number of injections. The mean daily insulin dose was 33 U/day (24 U with 1 injection/day). CONCLUSION: The IDAHO study shows that insulin is effective in type 2 diabetics however, management is inadequate with insulin therapy being initiated too late and at doses which are low after one year.     

Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre study.

AIMS: To evaluate the long-term effectiveness and safety of repaglinide, a novel prandial glucose regulator, in comparison with glipizide in the treatment of patients with Type 2 diabetes. METHODS: Diet or tablet-treated patients with Type 2 diabetes (n = 256; age 40-75 years, body mass index (BMI) 20-35 kg/m2, HbA1c 4.2-12.8%), without signs of severe microvascular or macrovascular complications, were included in this double-blind, multicentre, parallel-group comparative trial. Patients were randomized at a 2:1 ratio to repaglinide, 1-4 mg at mealtimes, or glipizide, 5-15 mg daily. RESULTS: Changes in fasting blood glucose (FBG) and HbA1c during the 12 months of treatment showed a significant difference in favour of repaglinide. In oral hypoglycaemic agents (OHA)-naive patients, HbA1c decreased in the repaglinide and glipizide groups by 1.5% and 0.3%, respectively (P < 0.05 between groups). Fasting blood glucose decreased in the repaglinide group by 2.4 mmol/l and increased in the glipizide group by 1.0 mmol/l (P < 0.05 between groups). In the study population as a whole, repaglinide was able to maintain glycaemic control (HbA1c level) during the 1-year study period, whereas control deteriorated significantly with glipizide. Change in HbA1c from baseline was significantly better with repaglinide than with glipizide after 12 months (P < 0.05). In addition, FBG deteriorated significantly in the glipizide group compared with the repaglinide group (P < 0.05). No patients in either group experienced a major hypoglycaemic event; the number of patients experiencing minor hypoglycaemia was similar in the repaglinide and glipizide groups (15% and 19%, respectively). CONCLUSIONS: Repaglinide, given as a prandial glucose regulator, is shown to be an effective and safe treatment of patients with Type 2 diabetes, and is better than glipizide in controlling HbA1c and FBG levels, overall, and in OHA-naive patients.     

The impact of pioglitazone on glycemic control and atherogenic dyslipidemia in patients with type 2 diabetes mellitus

BACKGROUND: To evaluate the glycemic control, lipid effects, and safety of pioglitazone in patients with type 2 diabetes mellitus. DESIGN AND METHODS: Patients (n = 197) with type 2 diabetes mellitus, a hemoglobin A1c (HbA1c) > or = 8.0%, fasting plasma glucose (FPG) > 7.7 mmol/l (140 mg/dl), and C-peptide > 0.331 nmol/l (1 ng/ml) were enrolled in this 23-week multi-center (27 sites), double-blind clinical trial and randomized to receive either a placebo or pioglitazone HCl 30 mg (pioglitazone), administered once daily, as monotherapy. Patients were required to discontinue all anti-diabetic medications 6 weeks before receiving study treatment. Efficacy parameters included HbA1c fasting plasma glucose (FPG), serum C-peptide, insulin, triglycerides (Tg), and cholesterol (total cholesterol [TC], high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C]). Adverse event rates, serum chemistry, and physical examinations were recorded. RESULTS: Compared with placebo, pioglitazone significantly (P= 0.0001) reduced HbA1c (-1.37% points), FPG (-3.19 mmol/l; -57.5 mg/dl), fasting C-peptide (-0.076+/-0.022 nmol/l), and fasting insulin (-11.88+/-4.70 pmol/l). Pioglitazone significantly (P < 0.001) decreased insulin resistance (HOMA-IR; -12.4+/-7.46%) and improved beta-cell function (Homeostasis Model Assessment (HOMA-BCF); +47.7+/-11.58%). Compared with placebo, fasting serum Tg concentrations decreased (-16.6%; P = 0.0178) and HDL-C concentrations increased (+12.6%; P= 0.0065) with pioglitazone as monotherapy. Total cholesterol and LDL-C changes were not different from placebo. The overall adverse event profile of pioglitazone was similar to that of placebo, with no evidence of drug-induced elevations of serum alanine transaminase (ALT) concentrations or hepatotoxicity. CONCLUSIONS: Pioglitazone improved insulin resistance and glycemic control, as well as Tg and HDL-C - which suggests that pioglitazone may reduce cardiovascular risk for patients with type 2 diabetes.     

Increase in stable glycosylated haemoglobin after induction of poor glycaemic control

Eight insulin-treated diabetic patients in good glycaemic control were studied as out-patients with frequent determinations of stable glycosylated haemoglobin (HbA1c) before, during and after 1 week of induced poor glycaemic control. Stable HbA1c was determined by cation exchange chromatography after elimination of the labile fraction by incubation in saline (0.15 mol/l). The increase in mean blood glucose was significant on the first day of reduced insulin therapy and greatest after 1 week (6.9 +/- 3.9 mmol/l above basal values). Stable HbA1c increased significantly on day 7 of the reduced insulin treatment. The increase represented, on average, 0.009% of total haemoglobin per mmol/l increase in mean blood glucose per 24 h during the period of induced hyperglycaemia. After restoring insulin therapy, a significant decrease in blood glucose was achieved on day 1 and after 2 days, the blood glucose level was similar to before the study. There was no significant decrease in stable HbA1c within the first 2 weeks of improved glycaemia.     

Insulin lispro: a potential role in preventing nocturnal hypoglycaemia in young children with diabetes mellitus.

AIMS: The long duration of action of soluble insulin given in the evening could contribute to the high prevalence of nocturnal hypoglycaemia seen in young children with Type 1 diabetes mellitus (T1DM). We examined whether replacing soluble insulin with insulin lispro reduced this risk in children on a three times daily insulin regimen. METHODS: Open crossover study comparing insulin lispro vs. soluble insulin in 23 (16 boys) prepubertal children (age 7-11 years) with T1DM on three injections/day; long-acting isophane insulin remained identical. At the end of each 4-month treatment arm, an overnight 15-min venous sampled blood glucose profile was performed. RESULTS: Despite similar blood glucose levels pre-evening meal (lispro vs. soluble: mean +/- se 6.5 +/- 1.0 vs. 7.1 +/- 1.1 mmol/l, P = 0.5), post-meal (18.00-22.00 h) blood glucose levels were lower on insulin lispro (area under curve 138 +/- 12 vs. 170 +/- 13 mmol min-1 l-1, P = 0.03). In contrast, in the early night (22.00-04.00 h) the prevalence of low blood glucose levels (< 3.5 mmol/l) was lower on lispro (8% of blood glucose levels) than on soluble insulin (13%, P = 0.01). In the early morning (04.00-07.00 h) mean blood glucose and prevalence of low levels were no different between the two treatment groups, and fasting (07.00 h) blood glucose levels were similar (6.1 +/- 0.8 vs. 6.3 +/- 0.9 mmol/l, P = 0.8). At the end of each treatment arm there were no differences in HbA1c (lispro vs. soluble 8.6% vs. 8.4%, P = 0.3), or in insulin doses (mean, range 0.97, 0.68-1.26 vs. 0.96, 0.53-1.22 U/kg per day, P = 0.2). CONCLUSIONS: The shorter duration of action of insulin lispro given before the evening meal may reduce the prevalence of early nocturnal hypoglycaemia without compromising HbA1c in young children with T1DM.     

Insulin glargine benefits patients with type 2 diabetes inadequately controlled on oral antidiabetic treatment: an observational study of everyday practice in 12,216 patients

AIMS: This observational study aimed to investigate the long-term efficacy and safety of adding insulin glargine (LANTUS((R))) to support oral antidiabetic (OAD) treatment in patients with type 2 diabetes in everyday practice. METHODS: A 9-month, open-label, multicentre, observational study, with an optional 20-month extension phase, in which add-on insulin glargine therapy was initiated in 12,216 patients with type 2 diabetes inadequately controlled on OADs. The insulin glargine dose was adjusted at the physician's discretion, reflecting everyday practice. The main outcome measures were changes in HbA(1c), fasting blood glucose (FBG), insulin dose and body mass index (BMI). RESULTS: At baseline, mean (+/- s.d.) age was 63.9 +/- 11.3 years; disease duration was >5 years in 47% of patients, 1-5 years in 39% of patients and <1 year in 10% of patients, while 4% of patients were newly diagnosed. Addition of insulin glargine to OAD therapy led to reductions in mean HbA(1c) (-1.5% from 8.7%) and FBG (-69 mg/dl from 202 mg/dl) levels after 3 months, which were maintained after 9 months [HbA(1c): -1.7%; FBG: -71 mg/dl (-3.9 mmol/l)] without an increase in BMI. Similar glycaemic control was observed after 20 months in the 2721 patients in the extension study. Adverse drug reactions were documented in 26 patients (0.2%). Of 47 adverse events documented, 19 were due to hypoglycaemia. CONCLUSIONS: In everyday practice, patients with type 2 diabetes who are inadequately controlled on OADs benefit from add-on basal insulin treatment with insulin glargine as they demonstrate improved glycaemic control without weight gain.     

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.     

Prandial insulin substitution with insulin lispro or insulin lispro mid mixture vs. basal therapy with insulin glargine: a randomized controlled trial in patients with type 2 diabetes beginning insulin therapy

PURPOSE: To compare the effects of prandial insulin therapy focusing on postprandial glucose control vs. basal insulin therapy focusing on fasting glucose control in patients with type 2 diabetes. METHODS: This was an open-label, randomized, parallel, three-arm multicenter trial in patients with type 2 diabetes starting insulin treatment. Patients (n=159) were randomly assigned to 24-week treatment with 3x daily insulin lispro, 3x daily lispro mid mixture (MidMix; 50% lispro, 50% protaminated lispro), or 1x daily insulin glargine; oral antihyperglycemic agents were discontinued. Primary end point was the postprandial glucose excursion 2 h after breakfast at the end of study. Secondary outcomes included HbA1c, self-monitored blood glucose profiles, hypoglycemic episodes, body weight, and patient satisfaction. RESULTS: At the end of study, glucose excursions 2 h after breakfast were significantly lower with lispro and MidMix than with glargine (P<.001 for each vs. glargine): lispro, -0.6+/-2.0 mmol/l; MidMix, +0.8+/-2.4 mmol/l; glargine, +2.5+/-2.4 mmol/l. Fasting glucose decreases were significantly greater with glargine (-2.6+/-2.4 mmol/l) than with lispro or MidMix (-0.9+/-2.2 mmol/l; +0.9+/-1.8 mmol/l). Nevertheless, HbA1c decreased by 1.1% (lispro) and 1.2% (MidMix), vs. 0.3% with glargine. Hypoglycemic episodes were rare with 1-1.5 self-reported episodes per 100 patient-days. CONCLUSIONS: In patients with type 2 diabetes starting insulin, 3x daily prandial treatment with a rapid-acting analog focusing on postprandial glucose values enabled better control of postprandial and circadian blood glucose profiles than once-daily glargine, in spite suboptimal fasting glucose levels, which targets fasting glucose values. These results support studies suggesting that control of postprandial hyperglycemia plays a key role in achieving HbA1c targets.     

Titration and optimization trial for the initiation of insulin glargine 100 U/mL in patients with inadequately controlled type 2 diabetes on oral antidiabetic drugs

For patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control, addition of basal insulin is recommended, but titration and optimization of basal insulin therapy in primary care is not well understood. We conducted an observational trial in 2470 patients with T2DM who initiated insulin glargine 100 U/L (Gla-100) on top of oral antidiabetic drugs. Physicians were free to choose either a “Davies,” “Fritsche” or “individual” titration algorithm. We found that fasting blood glucose (FBG) and glycated haemoglobin (HbA1c) levels were effectively reduced by Gla-100; 65.9% of patients achieved the primary endpoint (FBG ≤6.1 mmol/L (110 mg/dL) or an individual HbA1c target). There were no significant differences in efficacy and safety between the algorithms used. The mean FBG decreased by 3.2 mmol/L (59 mg/dL) over 12 months, while the mean HbA1c decreased by 15.3 mmol/mol (1.4%)%. From a starting dose of 11.7 U/d, the Gla-100 dosage was 22.8 U/d at 12 months, with similar values in each group. Rates of hypoglycaemia were low and did not differ by titration algorithm. We conclude that Gla-100 was effective at reducing FBG and HbA1c, independent of the titration algorithm, but observed that algorithms were inconsistently applied in clinical practice.     

Insulin glargine in combination with nateglinide in people with Type 2 diabetes: a randomized placebo-controlled trial.

OBJECTIVE: To determine the effect of adding nateglinide to therapy with insulin glargine in adults with Type 2 diabetes previously treated with insulin and with poor blood glucose control. RESEARCH DESIGN AND METHODS: In this 16-week, double-blind, placebo-controlled study, people with Type 2 diabetes [n = 55, HbA(1c) 8.2 +/- 1.0 (+/- sd)%, duration of diabetes 12.8 +/- 6.0 years, duration of insulin treatment 6.0 +/- 4.0 years] were transferred to single bedtime injection of insulin glargine for a titration period of 4 weeks, and then randomized to nateglinide or matching placebo before meals in addition to insulin glargine. Metformin was continued if taken. Doses of insulin and oral medication were titrated to protocol for the treatment period of 12 weeks. RESULTS: Baseline-adjusted self-monitored capillary blood glucose concentration at 12 weeks was significantly lower with nateglinide + insulin glargine compared with placebo + insulin glargine after breakfast [difference -2.3 (95% confidence interval -4.4, -0.2) mmol/l, P = 0.030], before lunch [-2.5 (-4.6, -0.3) mmol/l, P = 0.029], and after lunch [-2.3 (-4.3, -0.4) mmol/l, P = 0.021], but not at other times. Baseline-adjusted HbA(1c) was not lower with nateglinide + insulin glargine as compared with placebo + insulin glargine [7.8 +/- 1.4 vs. 8.3 +/- 1.0%, difference -0.43 (-0.98, 0.12)%]. CONCLUSIONS: Addition of nateglinide before meals to once-daily insulin glargine in people with long-standing diabetes already requiring insulin therapy improves blood glucose control in the early part of the day after breakfast and lunch, but does not provide good control of blood glucose levels overall.     

胰岛素治疗后血糖控制与2型糖尿病患者血浆同型半胱氨酸的关系

目的观察单纯胰岛素治疗的2型糖尿病患者,血糖控制水平与血浆总同型半胱氨酸（total homocysteine,tHcy）水平的关系。方法68例符合入选标准的2型糖尿病患者单纯给予胰岛素治疗3个月。基线和治疗3个月后取空腹血测定空腹血糖（FBG）、糖化血红蛋白（HbA1c）、tHcy,餐后2h取血测定餐后血糖（PBG）。结果所有患者经过3个月的单纯胰岛素治疗后,FBG、PBG和HbA1c均比治疗前显著下降（P〈0．01）。虽然治疗后血浆tHcy水平有下降趋势,但没有达到统计学显著水平（P〉0．05）。以HbA1c7．0％作为判断血糖控制水平的界值,治疗后HbA1c≤7．0％的患者31例（45．6％）,HbA1c〉7．0％的患者37例（54．4％）。治疗后HbA1c≤7．0％的患者,除FBG、PBG和HbA1c较治疗前显著下降外（P〈0．01）,tHcy也比治疗前显著降低（P〈0．01）。结论胰岛素强化治疗后,随着血糖控制改善,2型糖尿病患者血浆tHcy水平也明显下降。     

盐酸吡格列酮治疗2型糖尿病的有效性和安全性的多中心临床研究

目的　评价盐酸吡格列酮对 2型糖尿病患者合用磺脲类和双胍类药物时的降血糖作用 ,观察其安全性。方法　采用随机、双盲、安慰剂平行对照和多中心临床研究方法。对 2 83例应用磺脲类和双胍类治疗而血糖控制不佳 (7 0mmol/L≤空腹血糖 <13 0mmol/L)的 2型糖尿病患者随机分入吡格列酮 30mg组与安慰剂组治疗随访 6次共 12周。结果　于 12周时 ,试验组与对照组空腹血糖水平较基线值分别平均下降了 1 1mmol/L和 0 4mmol/L(P <0 0 0 1) ;餐后血糖分别下降了 1 5mmol/L和 0 3mmol/L(P <0 0 0 1) ;糖化血红蛋白 (HbA1c)分别下降了 0 7%和 0 4 % (P <0 0 1)。试验组空腹胰岛素下降幅度高于对照组 (P <0 0 5 ) ,其两组治疗前后的差值比较均分别具有显著性统计学差异。试验组HOMA IR显著降低 (P <0 0 1)。结论　 12周的临床观察显示 ,对 2型糖尿病患者饮食、运动和口服降糖药 (磺脲类和双胍类 )治疗控制不佳者联合应用吡格列酮 (30mg/d) ,代谢控制可得到进一步的改善 ,胰岛素的敏感性增强 ,安全性和耐受性好。     

A comparison of semisynthetic human NPH insulin and porcine NPH insulin in the treatment of insulin-dependent diabetes mellitus

Twenty-two insulin-dependent diabetic patients participated in a double-blind, cross-over study, where treatment with semisynthetic human NPH insulin (Novo Industri) was compared with porcine NPH insulin (Nordisk). Each treatment period lasted 8 weeks. Blood glucose level, glycosylated haemoglobin, insulin requirements, and frequency of hypoglycaemic events were compared. No difference was found in 24-hour blood glucose profiles. Fasting blood glucose level was 8.3 mmol/l during treatment with human insulin and 8.7 mmol/l during treatment with porcine insulin (p less than 0.1). Mean HbA1c was 7.7% at the end of study compared to 9.5% at baseline (p less than 0.01), but this decline in HbA1c was independent of the treatment regimen. Forty-six hypoglycaemic events occurred during treatment with human insulin compared to 39 events during treatment with porcine insulin. No difference was found regarding insulin requirements during the study. It is concluded that semisynthetic human NPH insulin is indistinguishable from porcine NPH insulin with respect to 24-hour blood glucose profile, HbA1c level and insulin dose requirements.     

Comparison of metabolic effects of pioglitazone, metformin, and glimepiride over 1 year in Japanese patients with newly diagnosed Type 2 diabetes.

AIMS: To compare the metabolic effects of pioglitazone, metformin, and glimepiride in the treatment of Japanese patients with newly diagnosed Type 2 diabetes. METHODS: A total of 114 patients with Type 2 diabetes who had never used oral hypoglycaemic drugs were studied for 12 months. Patients were randomly assigned to pioglitazone (30-45 mg/day, n = 38), metformin (750 mg/day, n = 39), or glimepiride (1.0-2.0 mg/day, n = 37). The effect of treatment on fasting plasma glucose (FPG), glycated haemoglobin (HbA(1c)), 1,5-anhydroglucitol (1,5AG), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, free fatty acids (FFA), and fasting plasma insulin levels was monitored monthly. Body weight and safety data were also collected. RESULTS: Eight patients withdrew from the study (three in the pioglitazone group, two in the metformin group, and three in the glimepiride group). The rate of reduction of HbA(1c) was fastest in patients receiving glimepiride and slowest in patients receiving pioglitazone. Although there were no significant differences among the three groups in HbA(1c) levels at the end of the study, patients taking pioglitazone had relatively lower FPG and 1,5AG levels than patients taking the other two drugs. These results suggest that pioglitazone acts predominantly on nocturnal metabolism rather than at mealtimes. FFA were reduced significantly in those taking pioglitazone (542.2 microEq/l vs. 237.3 microEq/l; P < 0.01) before a decrease in HbA(1c) was apparent. The change in FFA levels correlated with the change in HbA(1c) (r = 0.409, P < 0.01). There were no significant differences in other lipid parameters among the groups. CONCLUSIONS: Pioglitazone, metformin, and glimepiride are equally effective in reducing blood glucose in patients with newly diagnosed Type 2 diabetes. However, their specific characteristics, such as the rapid action on blood glucose levels of glimepiride and the favourable action on FPG and FFA of pioglitazone, should be considered when choosing an appropriate agent.     

Glargine is superior to neutral protamine Hagedorn for improving glycated haemoglobin and fasting blood glucose levels during intensive insulin therapy

AIM: To compare glycaemic control and symptomatic hypoglycaemia rates with glargine versus neutral protamine Hagedorn (NPH) in poorly controlled type 1 diabetes patients. METHODS: Patients (n = 125) received preprandial insulin lispro and either glargine (n = 62) or NPH (n = 63) at bedtime for 30 weeks in a multicentre, randomized, single-blind (a blinded investigator made titration decisions) study. Basal insulin dosage was titrated to achieve fasting blood glucose (FBG) values < 5.5 mmol/L. RESULTS: Baseline characteristics were similar for the two groups (mean diabetes duration 17.5 +/- 10.1 years) except mean glycated haemoglobin (HbA(1c)), which was lower in the glargine versus NPH group (9.2 +/- 1.1% vs 9.7 +/- 1.3%; P < 0.02). At end-point, mean HbA(1c) was 8.3 versus 9.1% for the glargine versus NPH groups. Adjusted least-squares mean (LSM) change from baseline was -1.04 versus -0.51%, a significant treatment benefit of 0.53% for HbA(1c) in favour of glargine (P < 0.01). Mean baseline FBG were similar for the glargine and NPH groups (11.2 vs 11.4 mmol/L). The means for end-point FBG were 7.9 versus 9.0 mmol/L. Adjusted LSM change from baseline was -3.46 versus -2.34 mmol/L, with a significant difference of 1.12 mmol/L in favour of glargine (P < 0.05). There were similar total numbers of daytime mild, moderate or severe hypoglycaemia episodes in the two treatment arms. However, significantly fewer moderate or severe nocturnal hypoglycaemic episodes were observed in the glargine group (P = 0.04 and P = 0.02). CONCLUSION: Glargine is superior to NPH for improving HbA(1c) and FBG levels during intensive insulin therapy in patients with type 1 diabetes, and is associated with less severe nocturnal hypoglycaemia.     

不同病程初发2型糖尿病对胰岛素短期强化治疗的反应

目的糖尿病初期胰岛素强化治疗可改善胰岛β细胞功能,但治疗时机尚无一致意见。本研究分析了不同病程初发2型糖尿病患者短期胰岛素强化治疗的胰岛β细胞功能改善程度。方法对2007年2月以来我科诊治的空腹血糖≥11.1mmol/L的初发2型糖尿病患者91例进行胰岛素强化治疗,对糖尿病病程在1周内组(A组,n=41)和12周以上组(B组,n=29)的患者进行分析总结。患者均行口服糖耐量试验测血糖和胰岛素、糖化血红蛋白(HbA1c)、糖化血清蛋白、血脂、尿酸、肝肾功能。每日4次三短一中胰岛素强化治疗4周后复测上述指标。采用稳态模型(HOMA)计算胰岛素抵抗指数(HOMA-IR)和胰岛素分泌指数(HOMA-β)。结果 A组和B组患者治疗后与治疗前相比,空腹血糖、糖化血清蛋白、HbA1c、甘油三酯、胆固醇、低密度脂蛋白胆固醇、收缩压和舒张压均有明显下降(P0.05),尿酸水平有所上升(P0.05),但两组相比无差异。两组患者强化治疗4周后HOMA-IR较治疗前无差异,而HOMA-β较治疗前有明显改善(P0.05),A组HOMA-β改善程度好于B组(P0.05)。以强化4周后HOMA-β为因变量,进行多因素回归分析,影响因素有体重指数、血压、甘油三酯水平、血糖达标时间、治疗前后HbA1c和糖化血清蛋白差值。结论糖尿病病程1周内进行强化治疗,胰岛β细胞功能改善好于病程12周以上,说明病程越短治疗效果越好。     

Comparative study on the efficacy of pioglitazone in Caucasian and Maori-Polynesian patients with poorly controlled type 2 diabetes

AIM: Although the pharmodynamic properties of the thiazolidinedione (TZD) insulin-sensitizing agents in the treatment of type 2 diabetes are well established, there are no studies comparing the pharmacoefficacy of these drugs in different ethnic groups. The aim of this pilot, prospective study was to examine the hypothesis that the efficacy of TZDs may vary depending on ethnicity. This aim was achieved by comparing the effects of 6-months treatment with pioglitazone (45 mg/day) on glucose control and metabolic and cardiovascular risk factors in Caucasian and Maori-Polynesian patients with poorly controlled type 2 diabetes. METHODS: Ninety-seven patients (40 Caucasian and 57 Maori-Polynesian) with type 2 diabetes were selected for the study from our clinical databases if they were on the maximum tolerated dose of oral agents and had a haemoglobin A(1c) (HbA(1c)) > 8.0% for at least 2 months. All the patients received pioglitazone (45 mg/day) for 6 months in addition to their regular diabetes therapy. Clinical data and blood samples were collected at monthly intervals and the following indices measured: weight, blood pressure, oedema score, HbA(1c), plasma glucose, alanine amino transferase and adiponectin levels and plasma lipid profile, including low-density lipoprotein (LDL)-cholesterol particle size and atherogenic index of plasma (AIP). The data of the 81 patients who finished the study were analysed using analysis of variance, chi-square analysis and multiple regression methods. RESULTS: The absolute change from baseline in mean HbA(1c) (Caucasian -1.4% vs. Maori-Polynesian -1.3%) and fasting glucose levels (Caucasian -2.1 mmol/l vs. Maori-Polynesian -2.8 mmol/l) was similar in the two groups. Pioglitazone caused an improvement in lipid profile in both ethnic groups, with a reduction in mean values of atherogenic fractions (triglyceride: Caucasian -0.5 mmol/l, p < 0.001 vs. Maori-Polynesian -0.3 mmol/l, p = 0.05; very low-density lipoprotein (VLDL)-cholesterol: Caucasian -0.11 mmol/l, p = 0.001 vs. Maori-Polynesian -0.04 mmol/l, p = 0.85; VLDL-triglyceride: Caucasian -0.36 mmol/l, p < 0.001 vs. Maori-Polynesian -0.22 mmol/l, p = 0.14; apolipoprotein B: Caucasian -0.09 mmol/l, p = 0.03 vs. Maori-Polynesian -0.08 mmol/l, p = 0.18). These changes were associated with an increase in LDL-cholesterol particle size (Caucasian +0.23 nm, p = 0.05 vs. Maori-Polynesian +0.26 nm, p = 0.04) and a decrease in AIP (Caucasian -0.14, p < 0.001 vs. Maori-Polynesian -0.08, p = 0.04). While the changes in the lipid indices tended to be greater in the Caucasian group, the difference in lipid response between the two ethnic groups was not statistically significant. Multiple regression analyses showed that the baseline value of the individual lipid fractions was the main determinant of the changes in lipid levels. CONCLUSIONS: These results demonstrated that pioglitazone has similar beneficial effects on glucose control and plasma lipid profile in Caucasian and Maori-Polynesian patients with poorly controlled type 2 diabetes. Our data showed that while the improvement in lipid profile was more pronounced in Caucasian patients than in Maori-Polynesian patients, this difference was not statistically significant.