Basal insulin glargine (HOE 901) versus NPH insulin in patients with type 1 diabetes on multiple daily insulin regimens. U.S. Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group

OBJECTIVE: Insulin glargine (HOE 901, 21(A)-Gly-30(B)a-L-Arg-30(B)b-L-Arg human insulin) is a novel recombinant analog of human insulin with a shift in the isoelectric point producing a retarded absorption rate and an increased duration of action that closely mimics normal basal insulin secretion. It recently received approval from the Food and Drug Administration. The aim of this study was to evaluate 2 formulations of insulin glargine for safety and efficacy in the treatment of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a 4-week trial, 256 patients with type 1 diabetes received either NPH insulin or insulin glargine containing 30 microg/ml zinc (insulin glargine[30]) or 80 microg/ml zinc (insulin glargine[80]). Insulin glargine was given subcutaneously once daily at bedtime. NPH insulin was given either once daily (at bedtime) or twice daily (before breakfast and at bedtime), according to the patient's prestudy regimen. The initial doses of insulin glargine and NPH were based on the previous NPH total daily dose. RESULTS: At study end point, insulin glargine-pooled groups had significantly lower fasting plasma glucose (FPG) levels than the NPH insulin group, with adjusted mean FPG levels reduced by 2.2 mmol/l (P = 0.0001). Insulin glargine was superior to NPH insulin in reducing FPG levels in patients who had previously received NPH insulin twice daily but not in patients who had previously received NPH once daily. FPG levels were more stable in patients using insulin glargine than in patients using NPH insulin. A subset of patients (n = 71) underwent hourly overnight plasma glucose measurements. Insulin glargine patients exhibited lower FPG levels after 5:00 A.M.; the difference was significant by 8:00 A.M. The adjusted mean FPG for insulin glargine[30] was 7.8 mmol/l; for insulin glargine[80], 7.3 mmol/l; and for NPH, 10.7 mmol/l. Both formulations of insulin glargine were well tolerated, similar to NPH insulin. CONCLUSIONS: Basal insulin glargine administered once daily for 4 weeks as part of a basal-bolus multiple daily insulin regimen was safe and more effective in lowering fasting plasma glucose levels than NPH in patients with type 1 diabetes.     

Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group

OBJECTIVE: Available basal insulin formulations do not provide a constant and reliable 24-h insulin supply. We compared the efficacy and safety of glargine (a long-acting insulin analog) and NPH insulins in insulin-naive type 2 diabetic patients treated with oral antidiabetic agents. RESEARCH DESIGN AND METHODS: There were 426 type 2 diabetic patients (age 59 +/- 9 years, BMI 28.9 +/- 4.3 kg/m2, mean +/- SD) with poor glycemic control on oral antidiabetic agents randomized to treatment for 1 year with bedtime insulin glargine or bedtime NPH insulin. Oral agents were continued unchanged. The fasting blood glucose (FBG) target was 6.7 mmol/l (120 mg/dl). RESULTS: Average glycemic control improved similarly with both insulins (HbA(1c), [reference range <6.5%] 8.3 +/- 0.1 vs. 8.2 +/- 0.1% at 1 year, glargine vs. NPH, mean +/- SEM, P < 0.001 vs. baseline for both). However, there was less nocturnal hypoglycemia (9.9 vs. 24.0% of all patients, glargine vs. NPH, P < 0.001) and lower post-dinner glucose concentrations (9.9 +/- 0.2 vs. 10.7 +/- 0.3 mmol/l, P < 0.02) with insulin glargine than with NPH. Insulin doses and weight gain were comparable. In patients reaching target FBG, HbA(1c) averaged 7.7 and 7.6% in the glargine and NPH groups at 1 year. CONCLUSIONS: Use of insulin glargine compared with NPH is associated with less nocturnal hypoglycemia and lower post-dinner glucose levels. These data are consistent with peakless and longer duration of action of insulin glargine compared with NPH. Achievement of acceptable average glucose control requires titration of the insulin dose to an FBG target < or =6.7 mmol/l. These data support use of insulin glargine instead of NPH in insulin combination regimens in type 2 diabetes.     

Reduced hypoglycemia risk with insulin glargine: a meta-analysis comparing insulin glargine with human NPH insulin in type 2 diabetes

OBJECTIVE: Insulin glargine (LANTUS) is a once-daily basal insulin analog with a smooth 24-h time-action profile that provides effective glycemic control with reduced hypoglycemia risk (particularly nocturnal) compared with NPH insulin in patients with type 2 diabetes. A recent "treat-to-target" study has shown that more patients on insulin glargine reached HbA(1c) levels < or =7.0% without confirmed nocturnal hypoglycemia compared with NPH insulin. We further assessed the risk for hypoglycemia in a meta-analysis of controlled trials of a similar design for insulin glargine versus once- or twice-daily NPH insulin in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: All studies were 24-28 weeks long, except one 52-week study, for which interim 20-week data were used. RESULTS: Patient demographics were similar between the insulin glargine (n = 1,142) and NPH insulin (n = 1,162) groups. The proportion of patients achieving target HbA(1c) (< or =7.0%) was similar between insulin glargine-and NPH insulin-treated patients (30.8 and 32.1%, respectively). There was a consistent significant reduction of hypoglycemia risk associated with insulin glargine, compared with NPH insulin, in terms of overall symptomatic (11%; P = 0.0006) and nocturnal (26%; P < 0.0001) hypoglycemia. Most notably, the risk of severe hypoglycemia and severe nocturnal hypoglycemia were reduced with insulin glargine by 46% (P = 0.0442) and 59% (P = 0.0231), respectively. CONCLUSIONS: These results confirmed that insulin glargine given once daily reduces the risk of hypoglycemia compared with NPH insulin, which can facilitate more aggressive insulin treatment to a HbA(1c) target of < or =7.0% in patients with type 2 diabetes.     

Insulin therapy in type 2 diabetes: role of the long-acting insulin glargine analogue

Insulin glargine is a long‐acting insulin analogue, with a longer duration of action and a flatter time‐action profile compared with NPH insulin. These properties can be predicted to result in higher glucose levels during the night and lower glucose levels after dinner following bedtime injection of insulin glargine compared with an equal dose of NPH insulin injected at bedtime. In two large‐scale clinical trials involving either insulin‐naïve (426 patients treated for 1 year) or previously insulin‐treated (518 patients treated for 28 weeks) patients with type 2 diabetes, comparing addition of once‐daily insulin glargine or NPH insulin to oral agents, these predictions were proven to be correct. Nocturnal hypoglycaemia was reduced by 58% in insulin‐naive patients and by 22% in previously insulin‐treated patients, and dinner‐time glucose control was significantly better with insulin glargine than with NPH insulin once daily in the study in insulin‐naive patients. The ‘treat‐to‐target study’ (756 insulin‐naive patients treated for 24 weeks) showed that good glycaemic control can be achieved with aggressive titration of the insulin dose with either once‐daily insulin glargine or NPH insulin combined with oral agents (mean endpoint HbA_1c was 6·96% with insulin glargine and 6·97% with NPH insulin); however, this was achieved with less variability and nocturnal hypoglycaemia with insulin glargine. These data support use of insulin glargine instead of NPH insulin for basal insulin replacement in patients with type 2 diabetes.     

Flexible intensive insulin therapy in adults with type 1 diabetes and high risk for severe hypoglycemia and diabetic ketoacidosis

OBJECTIVE: Diabetes treatment and teaching programs (DTTPs) for type 1 diabetes, which teach flexible intensive insulin therapy to enable dietary freedom, have proven to be safe and effective in routine care. This study evaluates DTTP outcomes in patients at high risk for severe hypoglycemia and severe ketoacidosis. RESEARCH DESIGN AND METHODS: There were 96 diabetes centers that participated between 1992 and 2004. A total of 9,583 routine-care patients with type 1 diabetes were examined before and 1 year after a DTTP. History of repeated severe hypoglycemia/severe ketoacidosis was an indication for DTTP participation. Before-after analyses were performed for subgroups of patients with three or more episodes of severe hypoglycemia or two or more episodes of severe ketoacidosis during the year before a DTTP. Main outcome measures were GHb, severe hypoglycemia, severe ketoacidosis, and hospitalization. RESULTS: A total of 341 participants had three or more episodes of severe hypoglycemia the year before a DTTP. Mean baseline GHb was 7.4 vs. 7.2% after the DTTP, incidence of severe hypoglycemia was 6.1 vs. 1.4 events x patient(-1) x year(-1), and hospitalization was 8.6 vs. 3.9 days x patient(-1) x year(-1). In mixed-effects models taking effects of centers and diabetes duration into account, mean difference was -0.3% (95% CI -0.5 to -0.1%; P = 0.0006) for GHb and -4.7 events x patient(-1) x year(-1) (-5.4 to -4; P < 0.0001) for severe hypoglycemia. A total of 95 patients had two or more episodes of severe ketoacidosis. GHb was 9.4% at baseline versus 8.7% after DTTP; incidence of severe ketoacidosis was 3.3 vs. 0.6 events x patient(-1) x year(-1), and hospitalization was 19.4 vs. 10.2 days x patient(-1) x year(-1). In linear models with diabetes duration as the fixed effect, the adjusted mean difference was -2.7 events x patient(-1) x year(-1) (95% CI -3.3 to -2.1; P < 0.0001) for severe ketoacidosis and -8.1 days (-12.9 to -3.2; P = 0.0014) for hospitalization. CONCLUSIONS: Patients at high risk for severe hypoglycemia or severe ketoacidosis may benefit from participation in a standard DTTP for intensive insulin therapy and dietary freedom.     

Dose-Response Effects of Insulin Glargine in Type 2 Diabetes

OBJECTIVE

To determine the pharmacokinetic and pharmacodynamic dose-response effects of insulin glargine administered subcutaneously in individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS

Twenty obese type 2 diabetic individuals (10 male and 10 female, aged 50 ± 3 years, with BMI 36 ± 2 kg/m² and A1C 8.3 ± 0.6%) were studied in this single-center, placebo-controlled, randomized, double-blind study. Five subcutaneous doses of insulin glargine (0, 0.5, 1.0, 1.5, and 2.0 units/kg) were investigated on separate occasions using the 24-h euglycemic clamp technique.

RESULTS

Glargine duration of action to reduce glucose, nonessential fatty acid (NEFA), and β-hydroxybutyrate levels was close to or >24 h for all four doses. Increases in glucose flux revealed no discernible peak and were modest with maximal glucose infusion rates of 9.4, 6.6, 5.5, and 2.8 μmol/kg/min for the 2.0, 1.5, 1.0, and 0.5 units/kg doses, respectively. Glargine exhibited a relatively hepatospecific action with greater suppression (P < 0.05) of endogenous glucose production (EGP) compared with little or no increases in glucose disposal.

CONCLUSION

A single subcutaneous injection of glargine at a dose of ≥0.5 units/kg can acutely reduce glucose, NEFA, and ketone body levels for 24 h in obese insulin-resistant type 2 diabetic individuals. Glargine lowers blood glucose by mainly inhibiting EGP with limited effects on stimulating glucose disposal. Large doses of glargine have minimal effects on glucose flux and retain a relatively hepatospecific action in type 2 diabetes.Type 2 diabetes is a condition of relative or absolute insulin deficiency. Consequently, insulin replacement becomes a common and essential therapy in these individuals. Insulin therapy in type 2 diabetes can range from a single injection to basal-bolus replacement regimens with multiple daily injections. Insulin glargine is a soluble long-acting insulin analog that is widely used in clinical practice for basal insulin replacement.Numerous studies have investigated the clinical efficacy of insulin glargine in both type 1 and type 2 diabetes (1–3). Glargine has been found to lower A1C, provide effective basal insulin replacement, and reduce the risk of hypoglycemia (1–3). Despite the widespread use of glargine in clinical practice, there have been relatively few studies investigating the pharmacokinetic and pharmacodynamic characteristics of the insulin. Two studies have investigated subcutaneous doses of 0.3 and 0.35 U glargine in type 1 diabetic individuals (4,5). Other studies also using a 24-h glucose clamp technique have compared the pharmacokinetics and pharmacodynamics of single doses of glargine (0.5 and 0.8 units/kg) in patients with type 2 diabetes (6,7). These studies provide valuable information about single doses of glargine in patients with diabetes. Klein et al. (8) have also compared three doses of glargine (0.4, 0.8, and 1.4 units/kg) in type 2 diabetes during 24-h clamp studies using the Biostator. However, because the Biostator has been reported to limit maximal glucose infusions during a glucose clamp and also produce a wide variation of blood glucose concentrations around the target glucose value (9), we reasoned that further information regarding the dose-response characteristics of insulin glargine in patients with type 2 diabetes would also be useful. The aim of the present study was to use the 24-h euglycemic clamp technique to determine the pharmacokinetics and pharmacodynamics of differing large, single subcutaneous doses of glargine (similar to those used in clinical practice in treatment of obese insulin-resistant type 2 diabetic individuals). Isotope dilution methods were used to determine the effects of glargine on endogenous glucose production and glucose disappearance.     

Insulin degludec in type 1 diabetes: a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine

OBJECTIVE

Insulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes.

RESEARCH DESIGN AND METHODS

In this 16-week, randomized, open-label trial, participants (mean: 45.8 years old, A1C 8.4%, fasting plasma glucose [FPG] 9.9 mmol/L, BMI 26.9 kg/m²) received subcutaneous injections of IDeg(A) (600 μmol/L; n = 59), IDeg(B) (900 μmol/L; n = 60), or insulin glargine (IGlar; n = 59), all given once daily in the evening. Insulin aspart was administered at mealtimes.

RESULTS

At 16 weeks, mean A1C was comparable for IDeg(A) (7.8 ± 0.8%), IDeg(B) (8.0 ± 1.0%), and IGlar (7.6 ± 0.8%), as was FPG (8.3 ± 4.0, 8.3 ± 2.8, and 8.9 ± 3.5 mmol/L, respectively). Estimated mean rates of confirmed hypoglycemia were 28% lower for IDeg(A) compared with IGlar (rate ratio [RR]: 0.72 [95% CI 0.52–1.00]) and 10% lower for IDeg(B) compared with IGlar (RR: 0.90 [0.65–1.24]); rates of nocturnal hypoglycemia were 58% lower for IDeg(A) (RR: 0.42 [0.25–0.69]) and 29% lower for IDeg(B) (RR: 0.71 [0.44–1.16]). Mean total daily insulin dose was similar to baseline. The frequency and pattern of adverse events was similar between insulin treatments.

CONCLUSIONS

In this clinical exploratory phase 2 trial in people with type 1 diabetes, IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses, with reduced rates of hypoglycemia.Improved glucose control delays and prevents the development of macrovascular and microvascular complications in type 1 diabetes (1,2). Unfortunately, a large proportion of people with type 1 diabetes is still unable to reach or maintain recommended A1C levels (3). Tighter glycemic control is typically accompanied by increased risk of hypoglycemia, and a compromise has to be made in each individual between optimal glycemic control and the person’s tolerated frequency of hypoglycemia (4).Despite the advantages offered by current basal insulin analogs (5,6), hypoglycemia remains a treatment limitation (7,8), causing decreased conscious level, inconvenience, embarrassment, and anxiety and can, as a result, lead to increased food intake and decreased insulin dosage. These important and occasionally life-threatening consequences all have a significant impact on quality of life (9–11).Insulin degludec (IDeg) is a new-generation ultra-long-acting basal insulin. The ultra-long effect of IDeg is primarily a result of the slow release of IDeg monomers from soluble multihexamers that form after subcutaneous injection, resulting in a long half-life and a smooth and stable pharmacokinetic profile at steady state (12). These attributes are expected to provide improved glycemic control and to lower the risk of hypoglycemia, relative to currently available basal insulin analogs.The present clinical exploratory trial compared the efficacy, safety, and tolerability of two different IDeg formulations (IDeg(A) and IDeg(B)) with insulin glargine (IGlar), all in combination with insulin aspart (IAsp) as mealtime insulin, in people with type 1 diabetes.     

Randomized cross-over trial of insulin glargine plus lispro or NPH insulin plus regular human insulin in adolescents with type 1 diabetes on intensive insulin regimens

OBJECTIVE: To compare blood glucose control and incidence of nocturnal hypoglycemia in adolescents with type 1 diabetes on multiple injection regimens managed with either an insulin analog combination or NPH insulin plus regular human insulin. RESEARCH DESIGN AND METHODS: In a randomized cross-over study, 28 adolescents with type 1 diabetes on multiple injection therapy received either insulin glargine prebedtime plus lispro preprandially (LIS/GLAR) or NPH insulin prebedtime plus regular human insulin preprandially (R/NPH). During each 16-week treatment arm, subjects completed home blood glucose profiles, and at the end of each treatment arm, they were admitted for an overnight metabolic profile. A total of 25 subjects completed the study. RESULTS: Compared with R/NPH therapy, LIS/GLAR was associated with lower mean blood glucose levels (LIS/GLAR versus R/NPH): fasting (8.0 vs. 9.2 mmol/l, P < 0.0001), 2 h postbreakfast (8.1 vs. 10.7 mmol/l, P < 0.0005), prelunch (8.9 vs. 10.1 mmol/l, P < 0.01), and 2 h postlunch (8.0 vs. 9.5 mmol/l, P < 0.002). However, there was no difference in mean blood glucose levels before or after the evening meal. Incidence of nocturnal hypoglycemia on overnight profiles was 43% lower on LIS/GLAR compared with R/NPH therapy; however, there was no difference in rates of self-reported symptomatic hypoglycemia. Total insulin dose required to achieve target blood glucose control was lower on LIS/GLAR (1.16 IU/kg) compared with R/NPH therapy (1.26 IU/kg, P < 0.005), but there was no significant difference in HbA(1c) levels (LIS/GLAR versus R/NPH: 8.7 vs. 9.1%, P = 0.13). CONCLUSIONS: Combination therapy with insulin glargine plus lispro reduced the incidence of nocturnal hypoglycemia and was at least as effective as R/NPH insulin therapy in maintaining glycemic control in adolescents on multiple injection regimens.     

Influence of and optimal insulin therapy for a low-glycemic index meal in children with type 1 diabetes receiving intensive insulin therapy

OBJECTIVE—The purpose of this study was to quantify the effects of glycemic index on postprandial glucose excursion (PPGE) in children with type 1 diabetes receiving multiple daily injections and to determine optimal insulin therapy for a low–glycemic index meal.RESEARCH DESIGN AND METHODS—Twenty subjects consumed test breakfasts with equal macronutrient contents on 4 consecutive days; high–and low–glycemic index meals (glycemic index 84 vs. 48) were consumed with preprandial ultra-short-acting insulin, and the low–glycemic index meal was also consumed with preprandial regular insulin and postprandial ultra-short-acting insulin. Each child''s insulin dose was standardized. Continuous glucose monitoring was used.RESULTS—The PPGE was significantly lower for the low–glycemic index meal compared with the high–glycemic index meal at 30–180 min (P < 0.02) when preprandial ultra-short-acting insulin was administered. The maximum difference occurred at 60 min (4.2 mmol/l, P < 0.0001). Regular insulin produced a 1.1 mmol/l higher PPGE at 30 min compared with ultra-short-acting insulin (P = 0.015) when the low–glycemic index meal was consumed. Postprandial ultra-short-acting insulin produced a higher PPGE at 30 and 60 min compared with preprandial administration when the low–glycemic index meal was consumed. The maximum difference was 2.5 mmol/l at 60 min (P < 0.0001).CONCLUSIONS—Low–glycemic index meals produce a lower PPGE than high–glycemic index meals. Preprandial ultra-short-acting insulin is the optimal therapy for a low–glycemic index meal.The results of the Diabetes Control and Complications Trial (DCCT) established that intensive insulin therapy optimizes glycemic control and reduces the risk of long-term complications in people with type 1 diabetes (1). Subjects who matched carbohydrate amount and insulin dose demonstrated a further improvement in glycemic control (2). Consequently, carbohydrate amount is considered to be the most important dietary determinant of postprandial glucose control (3).Published educational programs regarding intensive insulin therapy do not consider the influence of carbohydrate type on metabolic control (4–7). Glycemic index ranks carbohydrate-containing foods on the basis of their ability to raise blood glucose levels (BGLs) for a standardized amount of carbohydrate (8). Glycemic index is dependent on the chemical structure of the carbohydrate and preparation methods, which influence the speed of carbohydrate digestion and absorption.Established dietary recommendations for children with type 1 diabetes advocate the consideration of glycemic index (9). Some evidence suggests that a low–glycemic index diet may improve the long-term glycemic control of people with type 1 diabetes (10) and that postprandial glucose excursion (PPGE) is improved when children receiving treatment with conventional insulin regimens consume low–glycemic index meals (11,12). A recent article demonstrated improved daily glycemic profiles when children receiving intensive therapy consumed low–glycemic index diets (13). However, the effect of glycemic index on the postprandial glucose response requires further exploration in children receiving intensive insulin therapy.Newer intensive regimens using ultra-short-acting insulin analogs have been shown to improve postprandial glycemic rise (14). The potential additional benefits of low–glycemic index meals are uncertain within this context. Moreover, the time action profile of ultra-short-acting insulin may be inappropriate for the prolonged and lower glycemic rise of low–glycemic index meals.Preprandial regular insulin, which has a more delayed onset, lower peak concentration, and longer duration of action compared with ultra-short-acting insulin (15,16), may better match the absorption profile of low–glycemic index foods. However, postprandial ultra-short-acting insulin has been demonstrated to produce higher PPGEs compared with preprandial administration (17,18), and this may be another alternative approach to optimizing insulin therapy for a low–glycemic index meal, as suggested by the British Dietetics Association in its 2005 consensus statement (19).Therefore, the primary aim of this study was to determine the effect of altering the glycemic index of a meal on postprandial glucose control in children with type 1 diabetes receiving multiple daily injection therapy. The secondary aim was to assess whether preprandial ultra-short-acting insulin remains the optimal insulin therapy for a low–glycemic index meal.     

2型糖尿病胰岛素强化治疗患者的低血糖原因分析及护理

目的通过检测2型糖尿病患者胰岛素强化治疗后血糖及低血糖症发作时的血糖,分析低血糖发生原因,提出相应护理措施.方法 104例40～78岁2型糖尿病初次使用胰岛素强化治疗病例进入本次研究.以10d为观察期限,监测各时点手指血糖,并在患者低血糖发作时及时监测.结果糖尿病无并发症组发生低血糖频率显著低于有并发症组,差别有显著性意义(P＜0.05, P＜0.01,P＜0.001).40～49岁年龄段组在运用胰岛素强化治疗后发生低血糖的频率显著低于其他3个年龄段组,差异有显著性意义(P＜0.05,P＜0.001),而50～59、60～69岁年龄段组发生低血糖频率的差异无统计学意义(P>0.05).相关分析显示,发生低血糖概率与年龄及并发症的个数呈正相关.结论① 2型糖尿病病例经胰岛素强化治疗之后,年龄和是否有并发症是决定低血糖发生概率的重要影响因素.②对年龄较大、并发症较多的2型糖尿病患者需加强卫生宣教,密切观察病情,严密监测血糖,在胰岛素强化治疗过程中随时调整胰岛素用量.     

Insulin glargine in combination with oral antidiabetic drugs as a cost-equivalent alternative to conventional insulin therapy in type 2 diabetes mellitus

BACKGROUND AND RATIONALE: Recent data suggest that insulin glargine might be a cost-effective alternative to conventional insulin therapy in patients with type 2 diabetes mellitus (T2DM). The aim of this observational study was to evaluate the treatment costs of insulin glargine in combination with oral antidiabetic drugs (OADs) compared with conventional insulin therapy in T2DM in everyday clinical practice. PATIENTS AND METHODS: Data were obtained from a cohort of 678 patients with T2DM not adequately controlled by OADs alone (HbA1c mean 9.1 +/- 1.7%). Patients received either insulin glargine in addition to oral therapy or were switched to conventional insulin therapy. Treatment and dosing decisions were made at the physician's discretion, reflecting everyday practice. Patients were followed for 2-4 months. Primary outcome parameters were total treatment costs and clinical efficacy. RESULTS: The two therapeutic regimens were equally effective in decreasing HbA1c to 7.8% (p < 10(-9)). Patients in the insulin glargine plus OAD group controlled their blood glucose level at endpoint with a median of 60 test strips per month and those in the conventional insulin therapy group with a median of 80 strips per month (p = 0.000000739). Total daily costs of insulin, needles, glycemic control and OAD treatment per patient were similar in the two treatment groups (insulin glargine group 1.91 Euro vs conventional group 1.99 Euro). CONCLUSION: The two treatment regimens were equally effective in improving glycemic control. These results were achieved with significantly lower insulin doses and fewer blood glucose test strips in the insulin glargine group, which therefore led to cost equivalence when compared with conventional insulin therapy.     

甘精胰岛素联合瑞格列奈治疗初诊2型糖尿病的研究

目的探讨甘精胰岛素联合瑞格列奈治疗初诊2型糖尿病的临床效果。方法将本院初诊2型糖尿病患者60例随机分为观察组和对照组,对照组给予中短效的预混胰岛素治疗,观察组给予甘精胰岛素联合瑞格列奈治疗,评估两组临床效果。结果治疗后两组患者FPG、2h PG、Hb Alc明显优于治疗前,两组比较差异均有统计学意义(P0.05)。治疗后观察组患者Hb Alc明显优于对照组,两组比较差异有统计学意义(P0.05)。两组均无明显的低血糖事件发生。结论甘精胰岛素联合瑞格列奈治疗初诊2型糖尿病的临床效果明确,值得应用。     

甘精胰岛素联合格列美脲治疗2型糖尿病疗效观察

目的观察甘精胰岛素联合格列美脲治疗2型糖尿病的疗效。方法收集50例口服降糖药血糖控制不达标的2型糖尿病患者,采用甘精胰岛素联合格列美脲治疗,观察患者用药前后的空腹血糖、餐后2h血糖以及糖化血红蛋白的变化情况。结果用药后患者的空腹血糖、餐后2h血糖及糖化血红蛋白均明显下降(P<0.05)。结论甘精胰岛素联合格列美脲可较好地控制2型糖尿病患者的血糖,且低血糖发生率低,方法安全简便,是糖尿病患者理想的治疗方案。     

Short-term intensive insulin therapy in newly diagnosed type 2 diabetes

OBJECTIVE: Type 2 diabetes is associated with defects in insulin secretion and insulin action. Hyperglycemia may aggravate these defects, a feature known as glucose toxicity. Previous studies have shown that acute correction of hyperglycemia in subjects with long-standing type 2 diabetes gives only short-term improvement in glycemic control after discontinuation of insulin. The current study attempts to identify any characteristics of patients with newly diagnosed type 2 diabetes (fasting glucose >11.0 mmol/l) who would have a long-term benefit, in terms of glycemic control, from a brief course of insulin therapy. RESEARCH DESIGN AND METHODS: A total of 16 subjects (52 +/- 2 years old [range 36-64], BMI 30.8 +/- 1.9 kg/m2) with newly diagnosed type 2 diabetes had a 2-3 week course of intensive insulin therapy that was then discontinued. RESULTS: Fasting glucose fell from 13.3 +/- 0.7 to 7.0 +/- 0.4 mmol/l, and this improvement was maintained at the 1-year follow-up (6.7 +/- 0.3 mmol/l). The insulin area under the curve for the posttreatment oral glucose tolerance test also improved (8,251 +/- 1,880 before therapy, 18,404 +/- 4,040 directly after insulin therapy, and 42,368 +/- 8,517 pmol.min at the 1-year follow-up). At 1 year, seven of the subjects maintained good glycemic control on diet therapy alone, eight required oral hypoglycemic agent (OHA) therapy, and one required insulin therapy. The distinguishing features of those who did not require OHA or insulin therapy were that they required less insulin during the active insulin therapy phase (0.37 +/- 0.05 vs. 0.73 +/- 0.07 units.kg(-1).day(-1)) and were able to attain a lower fasting serum glucose at the end of the period of insulin therapy (5.9 +/- 0.3 vs. 7.7 +/- 0.4 mmol/l). CONCLUSIONS: These results demonstrate that in newly diagnosed type 2 diabetes with elevated fasting glucose levels, a 2- to 3-week course of intensive insulin therapy can successfully lay a foundation for prolonged good glycemic control. The ease with which normoglycemia is achieved on insulin may predict those patients who can later succeed in controlling glucose levels with attention to diet alone.     

Modern insulin therapy for type 1 diabetes mellitus

Modern insulin therapy for Type 1 diabetes is part of a comprehensive treatment program designed to achieve and maintain blood glucose levels as close to normal as possible. The insulin regimens most likely to be successful approximate physiologic insulin delivery by combining basal and meal doses. Several options are available, including constant infusion by external pump and multiple daily injection therapy. Modern therapy affords major health benefits through improved blood glucose control, as well as lifestyle benefits associated with increased flexibility and spontaneity.     

Cost-effectiveness of Insulin Degludec Versus Insulin Glargine in Insulin-naive Chinese Patients With Type 2 Diabetes

Purpose

The goal of this study was to investigate the long-term economic outcomes of insulin degludec versus insulin glargine use in Chinese patients with type 2 diabetes mellitus (T2DM) whose oral antidiabetic drugs did not provide sufficient glycemic control.

Effects of exercise on the absorption of insulin glargine in patients with type 1 diabetes

OBJECTIVE: To study the effects of exercise on the absorption of the basal long-acting insulin analog insulin glargine (Lantus), administered subcutaneously in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 13 patients (12 men, 1 woman) with type 1 diabetes on a basal-bolus insulin regimen were studied. (125)I-labeled insulin glargine at the usual basal insulin dose was injected subcutaneously into the thigh on the evening (2100) before the study day on two occasions 1 week apart. Patients were randomly assigned to 30 min intense exercise (65% peak oxygen uptake [Vo(2peak)]) on one of these visits. The decay of radioactive insulin glargine was compared on the two occasions using a thallium-activated Nal gamma counter. Blood samples were collected at regular intervals on the study days to assess plasma glucose and insulin profiles. RESULTS: No significant difference was found in the (125)I-labeled insulin glargine decay rate on the two occasions (exercise vs. no exercise; repeated-measures ANOVA, P = 0.548). As expected, a significant fall in plasma glucose was observed over the exercise period (area under curve above fasting [DeltaAUC] glucose: -0.39 +/- 0.11 vs. -1.30 +/- 0.16 mmol . l(-1) . h(-1); nonexercise vs. exercise; P = 0.001), but insulin levels did not differ significantly on the two occasions (DeltaAUC insulin: -2.1 +/- 3.9 vs. 1.5 +/- 6.2 pmol . l(-1) . h(-1); nonexercise versus exercise; P = 0.507). CONCLUSIONS: An intense 30-min period of exercise does not increase the absorption rate of the subcutaneously injected basal long-acting insulin analog insulin glargine in patients with type 1 diabetes.