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The Impact of Insulin Glargine on Clinical and Humanistic Outcomes in Patients Uncontrolled on Other Insulin and Oral Agents: an Office- Based Naturalistic Study*

Posted on: Friday, 7 January 2005, 03:00 CST

Key words: A1C - Body mass index - Diabetes mellitus - Glycemic control - Hypoglycemia - Quality of life - Questionnaire

SUMMARY

Objective: Controlling blood glucose levels in patients with diabetes often requires aggressive treatment, which may in turn cause hypoglycemia and/or decreased health-related quality of life (HRQOL). Insulin glargine, a long-acting insulin, has shown benefits of decreased nocturnal hypoglycemia without significant weight gain, while providing good glycemie control in clinical trials. These benefits have often been reported in studies of less than 1 year duration. The objective of this study was to evaluate the effectiveness of insulin glargine over a 12-month period in a clinical practice setting, and measure its effects on HRQOL in a subset of patients.

Design and Methods: Patients with diabetes in a large private endocrinology practice were initiated on insulin glargine. Patients were divided into 2 cohorts: the first group included patients with type 1 diabetes (T1D, n = 135); the second group included patients with type 2 diabetes previously on insulin and/or oral agents (T2D, n = 180). The HRQOL subset analysis included 50 patients from the above study. Patients completed a 40-item questionnaire adapted from the Diabetes Symptom Checklist-Revised (DSC-R) and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) at weeks 0, 2, 6, 12, and 16.

Results: Patients in both cohorts experienced statistically significant decreases in mean ( SD) A1C: group T1D, -0.28 1.47 (P = 0.0307); group T2D, -0.60 1.51 (P < 0.0001), with no significant changes in body mass index. In the year following insulin glargine therapy, there were significantly fewer hypoglycemic events per patient than in the year prior to insulin glargine therapy (group T1D: -0.33, P = 0.002; group T2D: -0.20, P = 0.004). HRQOL subset analysis also revealed a significant decrease in A1C (P < 0.0001) after 16 weeks of therapy with insulin glargine. In this subset of patients, there was a significant improvement in overall well being (P = 0.0019), emotional well being (P = 0.003), total symptom scores (P < 0.0001), and total symptom distress (P < 0.0001). The limitations of the study are those inherently associated with naturalistic observational studies such as recall bias and compliance.

Conclusions: Insulin glargine use over a 12-month period in a clinical practice setting was shown to significantly improve A1C without adversely impacting weight or the occurrence of hypoglycemia. Significant improvements were also observed in HRQOL.

Introduction

Diabetes continues to be a major public health concern, affecting an estimated 18.2 million people in the United States or 6.3% of the population including, approximately 5.2 million people who remain undiagnosed1. Based on most recent estimates, among people aged 20 years and older, 1.3 million new cases of diabetes will be diagnosed each year1. The chronic complications of the disease affecting the blood vessels, eyes, kidneys, and peripheral nerves account for the high morbidity and mortality rates associated with diabetes. Diabetes is the leading cause of new blindness, nephropathy and endstage renal disease, and nontraumatic amputations among adults in the United States1"5. Hyperglycemia plays a crucial role in the pathogenesis of these microvascular diseases and may cause or contribute to macrovascular disease, including coronary heart disease and stroke2,3. Diabetes also adversely impacts healthrelated quality of life (HRQOL)6'7. A significant decrease in functional health status, for example in the categories of body care and movement, ambulation, home management, and work is reported, particularly as diabetic complications become more severe6"8. Glycemie control reduces the risk of diabetes complications4 and improves HRQOL8,9.

Insulin is the cornerstone of therapy for all patients with type 1 diabetes, and many patients with type 2 diabetes eventually require insulin for glycemie control10. Intensive glycemie control with insulin significantly reduces the risk of development and progression of microvascular complications in patients with type 1(11,12) and type 2 diabetes13-14. However, the risk of hypoglycemia is also greater in intensively treated patients in clinical trials11"14. In clinical practice, hypoglycemia associated with intensive insulin therapy is also a common complication, and the fear of it often leads to suboptimal glucose control and may lead to decreased HRQOL.

In addition, to achieve the tight glycemie control seen in clinical trials, multiple daily injections of insulin are often needed. Intermediate-acting insulin products, such as neutral protamine Hagedorn (NPH) and Lente insulin, do not provide 24-hour basal insulin effects and may produce high peak insulin concentrations that can increase the risk of nocturnal hypoglycemia15. Insulin glargine, a long-acting insulin analogue, improves blood glucose control and reduces the incidence of nocturnal hypoglycemia in patients with type 1 or type 2 diabetes, without significant weight gain16"19. The objective of this study was to evaluate the effectiveness of insulin glargine use over a 12- month period in a naturalistic clinical practice environment. In addition, because diabetes carries a great burden on physical and psychological well-being, changes in HRQOL over a 16-week period were also assessed in a subset of patients.

Methods

Patients and Study Design

This prospective, 12-month, observational study was undertaken at the Diabetes and Glandular Disease (DGD) Clinic, a 7-member endocrine specialty clinic in San Antonio, TX. Adult patients ≥ 18 years old with the diagnosis of type 1 or type 2 diabetes, regardless of prior medication history, were considered for inclusion in the study if they were available for the duration of the study and were able to comply with the treatment regimen. The exclusion criteria included pregnancy and glycosylated hemoglobin (AlC) < 7.0%.

The study protocol conformed to the globally accepted standards of Good Clinical Practices (as defined in the ICH E6 Guidelines for Good Clinical Practices, 1 May 1996), and in agreement with the latest revision of the Declaration of Helsinki (HongKong Amendment, Sept. 1989). The study protocol was reviewed and accepted by an independent Ethics Committee. Written informed consent was obtained from each patient participating in the study.

Treatment and Follow-up

All patients included in the study were initiated on insulin glargine (Lantust) between 20 April 2001 and 30 June 2002 and followed for 12 months in the DGD Clinic. Patients were divided into 2 cohorts based on type of diabetes. Group TlD included patients with type 1 diabetes who were previously on insulin, and Group T2D included patients with type 2 diabetes who were previously on insulin and/or oral agents. All patients had their AlC levels taken at baseline and were initiated on insulin glargine in accordance with product label information. The primary efficacy variable was change in AlC between baseline and study end point. Other efficacy measures included changes in weight, hypoglycemie events, hospitalizations, and sick days from baseline to study end point.

All patients initiating therapy with insulin glargine at the DGD Clinic were asked to participate in the HRQOL study. Patients who could not speak and/or write English were excluded from consideration. The first 50 consecutive patients to accept were included in the final analysis. All participants in the HRQOL subset study were required to complete a QOL instrument at baseline, and again at weeks 2, 6, 12, and 16 following initiation of insulin glargine. Measurements of AlC were taken at baseline, and at weeks 12 and 16.

Data Collection

The General Electric Centricity Physician Office EMR (Hillsboro, OR), an electronic medical records software, was used for practice management and to maintain patient records. Where data were incomplete, the database was supplemented with manual chart reviews.

This study reflects office-based clinical practice and as such patients were seen every 3 to 4 months. Data were collected on glycemie control, weight, hypoglycemie events, hospitalizations, and medication use prior to and following the 12-month study period. Baseline AlC and body mass index (BMI) were defined as the measurement closest to the start of insulin glargine, and within 120 days; follow-up measurements were defined as the closest measurement to 360 days from the start of insulin glargine treatment. Pre- and post-hospitalizations, and hypoglycemie events were defined as all events reported by patients during physician visits within 360 days prior and 360 days following initiation of insulin glargine, respectively. One limitation of this later measure is that hospitalizations were self-reported by patients and may reflect recall bias. As a practice routine in the clinic, all patients are asked to monitor their glucose level using a home glucose test and maintain a log book of measurements and hypoglycemie events, if any.

For the HRQOL analysis, patients also completed a 40-item QOL questionnaire adapted from the Diabetes Symptom Checklist-Revised (DSC-R)20 and the Medical OutcomesStudy 36-Item Short-Form Health Survey (SF-36)21 at baseline and again at weeks 2, 6, 12, and 16.

The DSC-R was used to assess the impact of common diabetes symptoms and symptom distress. The DSC-R consists of 34 questions grouped into 8 symptom subscales: hyperglycemia, hypoglycemia, psychological cognitive functioning, psychological fatigue, cardiovascular, neuropathic pain, neuropathic sensory, and ophthalmologic functioning. Patients indicate whether they experienced any of the listed symptoms (yes or no response) during the past month. For each symptom experienced, patients indicate the extent to which they were bothered (ranging from 'not at all', coded as 1, to 'excellent', coded as 5). Two summary scales are also calculated, representing total symptoms and total symptom distress. A lower score on DSC-R indicates an improvement in QOL.

The 5-item mental health scale from the SF-36 was used to assess overall emotional well-being21. General health perceptions were measured using the single-item rating of health from the SF-36. A higher score on these measures indicates an improvement in overall QOL.

Statistical Analysis

Demographic data and prior medication use were reported for each of the cohorts at baseline. Change in AlC, BMI, and hypoglycemia for each group from baseline to 12 months were compared using a paired f- test.

For the HRQOL analysis, scores for each subscale were plotted at each measurement point to estimate change over time. Missing values for a data point were not included in this analysis involving that time point.

Changes in AlC and QOL for the 4 main scores (change in general well-being, emotional well-being, total symptoms, and symptom distress) from baseline to 16 weeks were compared using a paired f- test. Means for each QOL domain were compared at baseline and 16 weeks for patients based on age, sex, diabetes type, and baseline AlC. The correlation between change in QOL and AlC was explored using Pearson's correlation coefficient.

All computations were done with SAS Version 8.2 statistical software (SAS Institute, Gary, NC). Significance was set at 0.05 for all statistical tests. All data are expressed as the mean SD and the statistical significance is provided.

Results

Of the 315 patients who met the inclusion criteria, 135 (42.9%) were in the TlD cohort and 180 (57.1%) in the T2D cohort (Table 1). The mean age overall was 51.26 17.03 years with slightly more female (52.4%) than male (47.6%) patients. Patients in T2D cohort were older than those in TlD, with a mean age of 58.54 12.65 versus 41.56 17.32 years, respectively. There were more whites in the TlD (68.1%) than in the T2D cohort (45.5%) (P = 0.0006). Hispanics comprised the majority of the non-white population in both groups, reflective of DGD Clinic's overall racial make up.

The 3 most common comorbid diagnoses for both cohorts were neuropathy (TlD 18.7%, T2D 22.9%, P = 0.3628), hyperlipidemia (TlD 10.4%, T2D 22.3%, P = 0.0058), and hypertension (TlD 6.7%, T2D 17.3%, P = 0.0054); followed by retinopathy, albuminuria, coronary heart disease, and peripheral vascular disease (Table 1).

Insulin usage before the switch to insulin glargine was variable among TlD patients and included insulin lispro (84.4%), NPH insulin (73.3%), and Ultralente insulin (61.5%), either alone or in combination. Among T2D patients, 87.5% used insulin, primarily NPH (72.6%), and 56.6% used insulin in combination with oral agents.

Table 1. Patient demographics at baseline

Clinical Outcome Measures

Glycemie Response

The median time from initiation of insulin glargine to baseline AlC measurement was O days (mean -1.32 days). The median time from baseline to follow-up AlC was 350 days (mean 350.5 days). Glycosylated hemoglobin levels decreased in both cohorts from baseline to study end point. At 12 months of therapy, patients in the TlD cohort had a mean decrease in AlC of 0.28 1.47 (P = 0.0307) and those in the T2D group had a mean reduction of 0.60 1.51 (P < 0.0001) (Figure 1).

Body Mass Index

Of the 315 patients who met the inclusion criteria, 252 had baseline and follow-up BMI measurements. The median time from baseline to follow-up BMI was 355 days (mean 355.5 days). Both cohorts showed a slight and statistically insignificant change in BMI from baseline to 12 months. TlD patients had a mean change of 0.22 3.57kg/m^sup 2^, (P = 0.513), and T2D patients 0.09 4.07kg/ m^sup 2^ (P = 0.796) (Figure 1).

Additional Outcomes

Pre- and post-period hospitalizations and hypoglycemie events were also recorded for patients in each cohort. There was a significant decrease in hypoglycemie events for both study cohorts. Hypoglycemie events occurred in 45.2% of TlD patients in the pre- period, compared with 31.1 % in the post-period with a mean decrease of 0.33 1.22 events (P = 0.002). Hypoglycemie events were reported in 32.2% of T2D patients in the pre-period compared with 28.4% in the post-period with a mean decrease of 0.20 0.92 (F = 0.004) (Figure 1).

Total reported hospitalizations also decreased during the study period although the results were not statistically significant. Patients in the T2D cohort experienced a mean of 0.40 pre-period and 0.36 post-period hospitalizations, while TlD patients experienced a mean of 0.23 pre-period and 0.21 post-period hospitalizations.

No clinically relevant laboratory abnormalities, changes in vital signs, or any adverse events were observed in any patient on insulin glargine therapy.

QOL Analysis

Patient Demographics

Of the 50 patients who participated in the QOL substudy, 44% were women and 56% were men. The mean age overall was 54.0 14.5 years. At baseline, the mean AlC level was 9.2%, and 45.5% of female and 53.6% of male patients had AlC levels greater than the median level of 8.9%. The majority of patients (68% female and 64% male) had prior insulin use, and 36% were previously on oral antidiabetic medications (Table 2).

Figure 1. Clinical outcomes at 12 months in patients with type 1 (TlD) and type 2 (T2D) diabetes treated with insulin glargine. *P < 0.05, **P < 0.001 vs. baseline

Table 2. Patient demographics at baseline: QOL subset

Table 3. Summary of scores: QOL subset

Summary of Scores

Consistent with the larger study population, there was a significant decrease in AlC from baseline to week 16, with a mean decrease of 1.47% (P < 0.0001) (Table 3).

The mean total symptoms improved significantly by 34.8%, with a decrease from a mean score of 29.1 at baseline to 19.9 at study end point (P < 0.0001). The mean total symptom distress scores also improved significantly by 42.6%, from a mean score of 15.7 at baseline to 9.0 at week 16 (P < 0.0001) (Figure 2). Significant improvement in mean total emotional (P = 0.003} and general well- being (P = 0.002) scores from baseline to week 16 was also noted. The greatest improvement in both of these categories was seen at week 12.

Significant improvement was evident in individual symptom scores for hyperglycemia, hypoglycemia, cognitive, fatigue, and sensory subscales (Figure 3). Hypoglycemia and fatigue had the greatest percent improvement from baseline. Hypoglycemia scores showed a 42.8% improvement at week 2 and 16 (P = 0.0004). Fatigue scores had the greatest improvement at weeks 12 (38.2%) and 16 (49.6%) (P < 0.0001). Hypoglycemia distress had the greatest percent improvement from baseline at week 2 (44.7%) and week 6 (36.2%) for the symptom distress scores. At week 12, the hyperglycemia distress score showed the greatest percent improvement by 53.8% from baseline, and fatigue had the greatest percent improvement by 55.6% from baseline at week 16.

Figure 2. Quality of life summary scores over a 16-week period for patients with type 1 (TlD) and type 2 (T2D) diabetes treated with insulin glargine. *P < 0.0001

Figure 3. Change in symptom scores over a 16-week period for patients with type 1 (TlD) and type 2 (T2D) diabetes treated with insulin glargine

Correlation Between A1C and QOL

Results after 16 weeks showed no significant correlation between changes in AlC and the 4 QOL domains. The correlation between change in AlC and QOL domains was strongest for total symptoms, with a correlation of 0.237 (P = 0.113) and also for symptom distress, with a correlation of 0.123 (P = 0.414).

Although not statistically significant, at baseline, patients whose AlC levels were above the median of 8.9%, with the exception of the cardiovascular and vision domains, had poorer QOL on 6 of the 8 symptom and symptom distress domains than did patients with AlC < 8.9%. These 'above median' patients had worse QOL for the two DSC-R summary scores, as well as the SF-36 general well-being summary score.

'Above median' patients also exhibited more improvement in symptom, symptom distress, and overall well-being scores compared with 'below median' patients. Total symptom (excluding distress symptom) scores from baseline to week 16 for 'below median' patients showed a 21% improvement, while 'above median' patients showed a 46.9% improvement (F = 0.0376). Total distress symptom scores improved by 30.6% for 'below median' patients and by 52.6% for 'above median' patients (P = 0.1578).

Type 1 vs. Type 2 Diabetics

The improvement in total symptom and total distress symptom scores from baseline to week 16 were similar for patients with TlD (33.1% and 46.8%, respectively, P = 0.4472) and with T2D (36.3% and 42.8%, respectively, F = 0.6312). The improvement in general well- being was greater than that for emotional wellbeing for patients with TlD (16.7% vs. 4.2%, F = 0.5418) and T2D (20.3% vs. 9.6%, P = 0.1738).

Discussion

The results of the present observational study are consistent with those of clinical studies indicating that insulin glargine safely and effectively reduces blood glucose levels with a reduced risk of hypoglycemia. In patients with type 1 diabetes, prior studies of 4 to 28 weeks have shown lower fasting plasma glucose levels and decrea\sed hypoglycemie events, particularly in nighttime hypoglycemia, in patients using insulin glargine than those using NPH insulin16-19,22. Similar results have been reported in patients with type 2 diabetes23,24.

In the present office-based open-label study, once-daily insulin glargine treatment over a 12-month period in patients with type 1 or type 2 diabetes, who were previously on a combination of diabetes regimens, was shown to significantly reduce AlC levels without a concomitant weight gain.

The beneficial effects of insulin glargine were also evident in the significantly reduced incidence of hypoglycemie events during the 12-month insulin glargine therapy compared to pre-treatment events. Patients also reported fewer hospitalizations while on insulin glargine than before initiation of therapy suggesting an improved physical state.

Issues of QOL are becoming increasingly important in the management of chronic diseases such as diabetes. Therefore, as a component of evidence based medicine, assessment of QOL should be part of ongoing patient care. Measurement of HRQOL in ambulatory clinic settings requires modest material and resource investment and is acceptable to both staff and patient. In the present study, general well-being and diabetes-specific QOL instruments were used to identify improvement in overall health and well-being among new insulin glargine users. Overall, QOL improved on all measures following baseline, and significant improvement was seen on the 4 main domains from baseline to 16 weeks. There was also a significant improvement in AlC over the 16-week study period in this subset of patients.

Although the change in AlC was not significantly correlated with the change in QOL over the study period, there was a difference in the baseline QOL of patients based on their baseline AlC. Patients whose AlC levels were above the median of 8.9%, at baseline had poorer QOL on most diabetes-specific measures as well as the general well-being measure than patients with AlC < 8.9%. Since AlC is affected by blood glucose control over a 6-month period, the 16- week study period may not have been long enough to detect an association between change in AlC and QOL domains.

In a 1-year study in patients with type 2 diabetes improved glycemie control was associated with improved HRQOL, but the improvement in HRQOL was greater in patients who had hyperglycemie complaints at baseline than those who did not, suggesting that symptoms of hyperglycemia may predict the strength of the association between Al C and QOL8.

This study, like any observational analysis has certain inherent limitations. All patients were previously receiving treatment; therefore, the results cannot be generalized to a treatment-na'ive population. Furthermore, these patients were receiving care from diabetes specialists in an endocrinology clinic, which may have had effects on QOL beyond the effect of insulin glargine. As discussed, hypoglycemie events and hospitalizations were self-reported by patients and may reflect recall bias.

This was a naturalistic, observational study in an office-based practice setting and as such formal clinical trial standards of data collection were not observed. All patients who participated in this study were treated with insulin glargine and thus no control group existed to compare treatment effects between randomized, controlled cohorts. Therefore, some of the effects could be associated with placebo effects or regression to the mean. On the other hand, the long-term follow up (12-month) should minimize the impact of any possible placebo effect. Although subjective response of the patient cohorts treated according to routine clinical practice were noted, compliance was not systematically measured and may represent another limitation of the study.

Conclusion

In this study, in a clinical practice setting, insulin glargine was shown to provide safe and effective glycmie control in patients with type 1 or type 2 diabetes without inducing weight gain or hypoglycemia. Insulin glargine also improved health-related quality of life which should be considered in the overall evaluation of healthcare outcomes. This study suggests that insulin glargine may provide a means of achieving better glucose control and have a positive impact on quality of life. Further studies are needed to determine if the quality of life improvement observed in clinical practice is correlated with improved glycemie control, and if the improvement persists over the long term.

Acknowledgement

This research was supported by a research grant from Aventis Pharmaceuticals, Bridgewater, NJ.

* Material in this paper was previously presented at 63rd Scientific Sessions of the American Diabetes Association, June 2003, New Orleans, LA (Abstract #s: 452382 and 452387)

[dagger] Lantus is a trade name of Aventis Pharmaceuticals, Bridgewater, NJ

References

1. National Institute of Diabetes and Digestive and Kidney Diseases. Diabetes Statistics. Available at: http:// diabetes.niddk.nih.gov/ dm/pubs/statistics/index.htm#7. [Accessed 26 Jan 2004]

2. Harris MI. Undiagnosed NIDDM: clinical and public health issues. Diabetes Care 1993; 16:642-52

3. Klein R. Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care 1995; 18:258-68

4. Stratton IM, Adler AI, Andrew H, Neil W, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR (on behalf of the U.K. Prospective Diabetes Study Group). Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. Br Med J 2000;321:405- 12

5. United States Renal Data System (USRDS). 2003 USRDS Annual Data Report. Available at: http://www.usrds.org/ atlas.htm. [Accessed 20 Oct 2003]

6. de Grauw WJ, van de Lisdonk EH, Behr RR, van Gerwen WH, van den Hoogen HJ, van Weel C. The impact of type 2 diabetes mellitus on daily functioning. Fam Pract 1999; 16:133-9

7. Quality of life in type 2 diabetic patients is affected by complications but not by intensive policies to improve blood glucose or blood pressure control (UKPDS 37). U.K. Prospective Diabetes Study Group. Diabetes Care 1999;22:1125-36

8. Goddijn PP, BiIo HJ, Feskens EJ, Groeniert KH, van der Zee KI, Meyboom-de Jong B. Longitudinal study on glycaemic control and quality of life in patients with Type 2 diabetes mellitus referred for intensified control. Diabct Med 1999; 16:23-30

9. Van der Does FE, De Neeling JN, Snoek FJ, Kostense PJ, Grootenhuis PA, Bouter LM, Heine RJ. Symptoms and wellbeing in relation to glycemie control in type II diabetes. Diabetes Care 1996;19:204-10

10. United Kingdom Prospective Diabetes Study 24: A 6-Year, Randomized, controlled trial comparing sulfonylurea, insulin, and metfbrmin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy. Ann Intern Med 1998; 128:165-75

11. The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin- Dependent Diabetes Mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1998;329:977-86

12. Writing Team for the Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA 2002;287:2563-9

13. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854-65

14. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-53

15. Rosskamp RH, Park G. Long-acting insulin analogs. Diabetes Care 1999;22(Suppl. 2):B109-13

16. Levien TL, Baker DE, White JR Jr, Campbell RK. Insulin glargine: a new basal insulin. Ann Pharmacother 2002;36: 1019-27

17. Raskin P, Klaff L, Bergenstal R, Halle JP, Donley D, Mecca T. A 16-week comparison of the novel insulin analog insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with type 1 diabetes. Diabetes Care 2000;23:1666-71

18. Rosenstock J, Park G, Zimmerman J. 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. Diabetes Care 2000;23:1137-42

19. Murphy NP, Keane SM, Ong KK, Ford-Adams M, Edge JA, Acerini CL, Dunger DB. 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. Diabetes Care 2003;26:799-804

20. Grootenhuis PA, Snoek FJ, Heine RJ, Bouter LM. Development of a type 2 diabetes symptom checklist: a measure of symptom severity. Diabet Med 1994;! 1:253-61

21. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473-83

22. Schober E, Schoenle E, Van Dyk J, Wernicke-Panten K. Pediatrie Study Group of Insulin Glargine. Comparative trial between insulin glargine and NPH insulin in children and adolescents with type 1 diabetes. Diabetes Care 2001;24:2005-6

23. Yki-Jarvinen H, Dressler A, Ziemen M. 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. Diabetes Care 2000;23:1130-6

24. Rosenstock J, Schwartz SL, Clark CM Jr, Park GD, Donley DW, Edwards MB. Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin. Diabetes Care 2001 ;24:631-6

CrossRef links are available in the online published version \of this paper: http://www.cmrojournal.com

Paper CMRO-2671_4, Accepted for publication: 23 August 2004

Published Online: 21 September 2004

doi: 10.1185/030079904X5526

Jerome S. Fischer1, Trent McLaughlin2, Litza Loza1, Rebecca Beauchamp1, Sherwyn Schwartz1 and Mark Kipnes1

1 Diabetes and Glandular Disease Clinic, San Antonio, TX, USA

2 NDCHealth, Phoenix, AZ, USA

Address for correspondence: Dr Jerome S. Fischer, Diabetes and Glandular Disease Clinic, 5107 Medical Drive, San Antonio, TX 78229, USA. Tel.: +1-210-615-5510; Fax: +1-210-614-7385; email: JSFisch@dgdclinic.com

Copyright Librapharm Nov 2004

Source: Current Medical Research and Opinion

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