Insulin-naive Patients Research Articles

Reduced Weight Gain with Insulin Detemir Compared to NPH Insulin Is Not Explained by a Reduction in Hypoglycemia

Weight gain often occurs when insulin therapy is initiated. The long-acting insulin analog insulin detemir has been shown to be effective and well tolerated when used in basal-bolus regimens or as an add-on to oral antidiabetic drugs (OADs) and causes less weight gain than other insulins. The aim of this exploratory analysis was to investigate any correlations between weight change and occurrence of hypoglycemia with NPH insulin and insulin detemir. The analysis was based on a 26-week, randomized, multicenter, open-label, parallel-group trial in which glycemic control, hypoglycemia, and weight change were compared between insulin detemir and NPH insulin. A total of 476 insulin-naive patients with type 2 diabetes treated with one or two OADs added insulin detemir (n=237) or NPH insulin (n=239) morning and evening to their current oral treatment. Weight gain data from this study were analyzed as a function of hypoglycemia frequency. Both groups achieved excellent glycosylated hemoglobin control (insulin detemir, 6.6%; NPH insulin, 6.5% [difference not significant]). Weight gain with insulin detemir was less than half that of NPH insulin (1.2 vs. 2.8 kg, respectively [P<0.001]), and the overall risk of hypoglycemia was 47% lower with insulin detemir (P<0.001). No significant relationship between hypoglycemia and weight gain was seen with insulin detemir (P=0.2), while a statistically significant correlation was found for NPH insulin (P=0.003). Hypoglycemia is predictive of weight gain with NPH insulin, but the same relationship is not seen with insulin detemir. It is therefore likely that the weight-sparing effect of insulin detemir involves other mechanisms.

Measuring Psychological Insulin Resistance

The purpose of this study is to explore the attitudes that contribute to psychological insulin resistance (PIR) in insulin-naive patients with type 2 diabetes and to identify predictors of PIR. A prospective study using 2 self-report surveys and incorporating demographic and health variables was conducted to determine the prevalence of PIR among a sample of 100 adult, insulin-naive patients with type 2 diabetes at an outpatient diabetes center in a university-affiliated teaching hospital. Thirty-three percent of patients with type 2 diabetes were unwilling to take insulin. The most commonly expressed negative attitudes were concern regarding hypoglycemia, permanent need for insulin therapy, less flexibility, and feelings of failure. Less than 40% expressed fear of self-injection or thought that injections were painful. However, compared with willing subjects, unwilling subjects were more likely to fear injections and thought injections would be painful, life would be less flexible, and taking insulin meant health would deteriorate (P< .005 for all comparisons). Poorer general health and higher depression scores also correlated with PIR. The results of the surveys, which were generally consistent, identified several remediable misconceptions regarding insulin therapy and suggest targets for educational interventions.

Effect of biphasic insulin aspart on glucose and lipid control in patients with Type 2 diabetes mellitus

Objective: this study examined the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) monotherapy in insulin-naive patients with Type 2 diabetes mellitus. Research design and methods: in this 12-week, open-labelled, uncontrolled, clinical-experience study involving 71 patients with secondary oral antidiabetic agent failure, patients received BIAsp 30 after discontinuing oral antidiabetic drugs (OADs). Glucose and lipid concentrations, hypoglycaemic episodes and adverse events were assessed before and after treatment. Patient data were categorised according to previous OADs into the biguanides (BI) plus sulfonylureas/meglitinides (SU/MEG) and SU-only groups. Results: after treatment, glucose and lipid control was significantly improved in both groups, with a greater improvement in the SU-only group. Mean glycated haemoglobin, fasting blood glucose and postprandial blood glucose excursion improved by 2.15 ± 1.24%, 3.70 ± 3.18 mmol/l and 1.26 ± 2.65 mmol/l in the BI plus SU/MEG group, and by 3.09 ± 1.62%, 6.11 ± 5.02 mmol/l and 2.06 ± 2.33 mmol/l in the SU-only group, respectively. Mean high-density lipoprotein cholesterol and triglycerides improved by 0.09 ± 0.18 mmol/l and 0.94 ± 1.17 mmol/l in the BI plus SU/MEG group and by 0.09 ± 0.18 mmol/l and 1.04 ± 2.72 mmol/l in the SU-only group, respectively. No major hypoglycaemic episodes or serious treatment-related adverse events were reported. Conclusions: our study showed that BIAsp 30 treatment safely improved glucose and lipid control in insulin-naive patients with Type 2 diabetes poorly controlled on BI plus SU/MEG and SU-only. Key limitations were the lack of a comparator group and the short study duration.

Comparison of biphasic insulin aspart 30 given three times daily or twice daily in combination with metformin versus oral antidiabetic drugs alone in patients with poorly controlled type 2 diabetes: A 16-week, randomized, open-label, parallel-group trial conducted in russia

Background: Modern premixed insulins offer a flexible approach to the initiation of insulin therapy in patients with poorly controlled type 2 diabetes. A disadvantage of twice-daily regimens of biphasic insulin aspart 30 (BIAsp 30) is that lunchtime control (when no insulin is administered) can be suboptimal. Therefore, it is possible that administering BIAsp 30 thrice daily might further optimize glycemic control and offer an option for patients in whom metformin (MET) is contraindicated. Objective: This study evaluated the efficacy and safety profiles of 2 different regimens of BIAsp 30 compared with a regimen consisting of oral antidiabetic drugs (OADs) alone. Methods: In this multicenter, randomized, open-label, parallel-group trial, insulin-naive patients with poorly controlled type 2 diabetes (baseline glycosylated hemoglobin [HbA 1c ≥8.0%) who were taking OADs (a sulfonylurea or meglitinide with/without MET or MET only) were randomized to receive BIAsp 30 TID, BIAsp 30 BID + MET, or continuation of their current OAD therapy for 16 weeks. The primary end point was HbA 1c at the end of the study. Secondary end points included reductions in HbA 1c, mean blood glucose (BG), prandial increment, mean 7-point self-monitored BG profile, weight changes, tolerability (hypoglycemia, adverse events), and satisfaction/quality of life (derived from 2 questionnaires completed at weeks 0, 8, and 16). Results: The study enrolled 308 insulin-naive patients with type 2 diabetes (78.9% female; mean age, 58.3 years; body mass index, 29.4 kg/m 2; HbA 1c, 10.3%). Both BIAsp 30 TID and BIAsp 30 BID + MET were associated with significantly greater mean (SD) reductions in HbA 1c relative to OADs alone (absolute percent reduction: 2.9% [1.5%], 3.0% [1.6%], and 2.1% [1.4%], respectively; P < 0.001, both insulin groups vs OAD group) and improved post-prandial glucose control (reduction in mean post-prandial glucose:−6.32 [4.07], −6.44 [4.70], and −3.59 [4.22] mmol/L; P < 0.001, both insulin groups vs OAD group). The mean decrease in the prandial increment was −1.26 mmol/L for BIAsp 30 TID, −2.15 mmol/L for BIAsp 30 BID + MET, and −0.44 mmol/L for OAD. The differences in reduction in the prandial increment were statistically significant for BIAsp 30 TID versus OAD ( P = 0.047), BIAsp 30 BID + MET versus OAD ( P < 0.001), and BIAsp 30 TID versus BIAsp 30 BID + MET ( P = 0.042). Mean body weight increased significantly from baseline with both BIAsp 30 TID and BIAsp 30 BID + MET (+1.71 and +1.50 kg, respectively; both, P < 0.001), and decreased significantly in the OAD group (−0.75 kg; P = 0.003). There were no major hypoglycemic events, and most hypoglycemic events were recorded as symptoms only (144/158 [91.1%]). There were no significant differences in the mean frequency of overall hypoglycemic episodes between BIAsp 30 TID and BIAsp 30 BID + MET (0.73 and 0.69 episodes per patient-year, respectively). Conclusions: In these patients with type 2 diabetes that was poorly controlled by OADs, BIAsp 30 TID and BIAsp 30 BID plus MET were associated with significantly greater reductions in HbA 1c and postprandial BG compared with OADs alone. The insulin regimens were associated with significantly more weight gain than OADs alone. There were no differences in rates of hypoglycemia between the insulin regimens.

Comparison of Once-Daily Glargine Plus Sulfonylurea with Twice-Daily 70/30 Aspart Premix in Insulin-Naive Japanese Patients with Diabetes

Type 2 diabetes patients insufficiently controlled with sulfonylurea (SU) are commonly treated by switching to twice-daily premix insulin replacing SU. The efficacy of glargine (GL) added on to SU compared with the premix therapy has not been analyzed in Japan. The open-label two-arm study was conducted in 30 type 2 diabetes patients poorly controlled [hemoglobin A(1c) (HbA(1c)) >7.5%] with SU with or without other oral hypoglycemic agents (OHAs). The GL group injected once-daily GL in addition to the OHAs. The aspart 70/30 (70/30) group discontinued SU among the OHAs and injected twice-daily 70/30. Patients were recommended either method in a block random method, and if twice-daily 70/30 was rejected, once-daily GL was selected only at the first time. The insulin dose was titrated to achieve a target fasting plasma glucose of <120 mg/dL and/or HbA(1c) of <7%. Nineteen of 20 patients treated with GL and 11 of 14 patients treated with 70/30 completed the 6-month study. Mean HbA(1c) improved from 8.45% to 7.5% in the GL group and from 9.13% to 7.93% in the 70/30 group. The mean HbA(1c) decrease during 6 months was -0.95% in the GL group and -1.20% in the 70/30 group (P = 0.49). Mean insulin doses at 6 months were 12.0 units/day for the GL group and 26.7 units/day for the 70/30 group. Both therapies were well tolerated without severe hypoglycemia. Once-daily GL injection added on to OHAs was equally safe and effective compared with twice-daily injection of aspart 70/30 premix replacing SU in type 2 patients insufficiently controlled with OHAs.

Clinical Research Observations with Use of Exubera in Patients with Type 1 and 2 Diabetes

Diabetes Technology & TherapeuticsVol. 9, No. s1 Invited PapersClinical Research Observations with Use of Exubera in Patients with Type 1 and 2 DiabetesWilliam T. Cefalu and Zhong Q. WangWilliam T. CefaluSearch for more papers by this author and Zhong Q. WangSearch for more papers by this authorPublished Online:11 Jun 2007https://doi.org/10.1089/dia.2007.0223AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byThe expanding role of aerosols in systemic drug delivery, gene therapy and vaccination: an update13 January 2014 | Translational Respiratory Medicine, Vol. 2, No. 1A Comparison Between Simplified and Intensive Dose-Titration Algorithms Using AIR Inhaled Insulin for Insulin-Naive Patients with Type 2 Diabetes in a Randomized Noninferiority Trial C. Mathieu, R. Cuddihy, R.F. Arakaki, R.M. Belin, J.-M. Planquois, J.N. Lyons, and C.R. Heilmann22 September 2009 | Diabetes Technology & Therapeutics, Vol. 11, No. s2Insulin Delivery via Lungs—Is It Still Possible? Satish K. Garg and William C. Kelly22 September 2009 | Diabetes Technology & Therapeutics, Vol. 11, No. s2Pure Insulin Nanoparticle Agglomerates for Pulmonary Delivery30 October 2008 | Langmuir, Vol. 24, No. 23Pharmaceutical Particle Engineering via Spray Drying28 November 2007 | Pharmaceutical Research, Vol. 25, No. 5Pulmonary Insulin Delivery—State of the Art 2007 Jay S. Skyler11 June 2007 | Diabetes Technology & Therapeutics, Vol. 9, No. s1 Volume 9Issue s1Jun 2007 InformationMary Ann Liebert, Inc.To cite this article:William T. Cefalu and Zhong Q. Wang.Clinical Research Observations with Use of Exubera in Patients with Type 1 and 2 Diabetes.Diabetes Technology & Therapeutics.Jun 2007.S-28-S-40.http://doi.org/10.1089/dia.2007.0223Published in Volume: 9 Issue s1: June 11, 2007PDF download

Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes (RABBIT 2 Trial)

We sought to study the optimal management of hyperglycemia in non-intensive care unit patients with type 2 diabetes, as few studies thus far have focused on the subject. We conducted a prospective, multicenter, randomized trial to compare the efficacy and safety of a basal-bolus insulin regimen with that of sliding-scale regular insulin (SSI) in patients with type 2 diabetes. A total of 130 insulin-naive patients were randomized to receive glargine and glulisine (n = 65) or a standard SSI protocol (n = 65). Glargine was given once daily and glulisine before meals at a starting dose of 0.4 units x kg(-1) x day(-1) for blood glucose 140-200 mg/dl or 0.5 units x kg(-1) x day(-1) for blood glucose 201-400 mg/dl. SSI was given four times per day for blood glucose >140 mg/dl. The mean admission blood glucose was 229 +/- 6 mg/dl and A1C 8.8 +/- 2%. A blood glucose target of <140 mg/dl was achieved in 66% of patients in the glargine and glulisine group and in 38% of those in the SSI group. The mean daily blood glucose between groups ranged from 23 to 58 mg/dl, with an overall blood glucose difference of 27 mg/dl (P < 0.01). Despite increasing insulin doses, 14% of patients treated with SSI remained with blood glucose >240 mg/dl. There were no differences in the rate of hypoglycemia or length of hospital stay. Treatment with insulin glargine and glulisine resulted in significant improvement in glycemic control compared with that achieved with the use of SSI alone. Our study indicates that a basal-bolus insulin regimen is preferred over SSI in the management of non-critically ill, hospitalized patients with type 2 diabetes.

Comparison of Standard (Self-Directed) Versus Intensive Patient Training for the Human Insulin Inhalation Powder (HIIP) Delivery System in Patients with Type 2 Diabetes: Efficacy, Safety, and Training Measures

The Lilly/Alkermes human insulin inhalation powder (HIIP) delivery system [AIR (a registered trademark of Alkermes, Inc., Cambridge, MA) Inhaled Insulin System] was designed to be easy to use. Training methods were compared in insulin-naive patients with type 2 diabetes. Patients (n = 102) were randomized to standard or intensive training. With standard training, patients learned how to use the HIIP delivery system by reading directions for use (DFU) and trying on their own. Intensive training included orientation to the HIIP delivery system with individual coaching and inspiratory flow rate training. Both groups received preprandial HIIP + metformin with or without a thiazolidinedione for 4 weeks. Overall 2-h postprandial blood glucose (PPBG) excursion was the primary measure. Noninferiority was defined as the upper limit of the two-sided 95% confidence interval of the mean difference between groups being 1.2 < or = mmol/L. Overall 2-h PPBG excursions (least squares mean +/- SE) at endpoint were -0.11 +/- 0.38 (standard training) and 0.23 +/- 0.36 (intensive training) mmol/L. The mean difference (standard minus intensive training) and two-sided 95% confidence interval were -0.35 (-1.02, 0.33) mmol/L. No statistically or clinically significant differences were observed between training methods in premeal, postmeal, or bedtime blood glucose values, HIIP doses at endpoint, or blood glucose values after a test meal. No discontinuations occurred because of difficulty of use or dislike of the HIIP system. DFU compliance was >90% in both training groups. There were no significant differences between training methods in safety measures. The HIIP delivery system is easy to use, and most patients can learn to use it by reading the DFU without assistance from health care professionals.

Combination of Oral Antidiabetic Agents with Basal Insulin Versus Premixed Insulin Alone in Randomized Elderly Patients with Type 2 Diabetes Mellitus

To compare initiation of insulin therapy by adding once-daily insulin glargine to oral antidiabetic agents (OADs) with switching patients to premixed 30% regular, 70% human neutral protamine hagedorn insulin (70/30) without OADs. A 24-week, multicenter, open, randomized (1:1), parallel study. Three hundred sixty-four poorly controlled patients with type 2 diabetes mellitus were treated with once-daily morning insulin glargine with continued OADs (glimepiride+metformin) (glargine+OAD) or twice-daily 70/30 alone. Insulin dosage in each group was titrated to target fasting blood glucose (FBG) of 100 mg/dL or less (<or=5.6 mmol/L) using a weekly titration algorithm. This planned subgroup analysis of the original study was based on 130 insulin-naive patients aged 65 and older with FBG of 120 mg/dL or greater (>or=6.7 mmol/L) and hemoglobin (Hb)A(1c) levels between 7.5% and 10.5% on OADs (glargine+OAD, n=67; 70/30, n=63). HbA(1c), FBG, hypoglycemia, insulin dose, and adverse events were recorded. HbA(1c) decreased from baseline to endpoint for both glargine+OAD (from 8.8% to 7.0%) and 70/30 (from 8.9% to 7.4%); adjusted mean HbA(1c) decrease for glargine+OAD and 70/30 was -1.9% and -1.4%, respectively (P=.003). More patients reached HbA(1c) of 7.0% or less without confirmed nocturnal hypoglycemia with glargine+OAD (n=37, 55.2%) than with 70/30 (n=19, 30.2%) (P=.006). FBG decreased significantly more with glargine+OAD (-57 mg/dL (-3.2 mmol/L)) than with 70/30 (-40 mg/dL (-2.2 mmol/L)) (P=.002). Patients treated with glargine+OAD experienced fewer episodes of any hypoglycemia (3.68/patient-year) than did those treated with 70/30 (9.09/patient-year) (P=.008). In elderly patients, addition of once-daily morning glargine+OAD is a simple regimen to initiate insulin therapy, restoring glycemic control more effectively and with less hypoglycemia than twice-daily 70/30 alone.

The role of basal insulin therapy in patients with type 2 diabetes mellitus

Background: The natural course of type 2 diabetes mellitus (DM) is characterized by insulin resistance followed by a progressive decline in β-cell function, which results in relative insulin deficiency. At diagnosis, a patient with tvpe 2 DM has only 50%, of β-cell function remaining. Given this inevitable decline in β-cell function and insulin secretion, most patients with type 2 DM will require insulin therapy at some point. Objective: The objective of this article was to provide a brief overview of physiologic insulin secretion and to discuss the role of basal insulin therapy in patients with type 2 DM. Methods: Materials for this article were identified through searches (2000–2005) of MEDLINE and Google, as well as from the author's personal files. Search terms included basal insulin, titration, hypoglycemia, glycemic control, and basal-bolus therapy. Results: The cfficacy of insulin either as nmonotherapy or in combination with oral agents in type 2 DM is well established. Insulin therapy has also been show to improve insulin sensitivity and, in some cases, reverse insulin resistance, possibly by elimination of glucose toxicity. In recent years, the availability of insulin formulations with more favorable pharmacokinetic profiles has reduced concerns about hvpoglycemia and weight gain, facilitating the use of insulin in patients with type 2 DM. For insulin-naive patients who are inadequately controlled on oral antidiabetic drugs, the addition of a single basal insulin dose at bedtime has been found to reduce glycosylated hemoglobin (A1C levels,with a low risk of nocturnal hypoglycemia. Basal insulins. (ie, glargine, detemir) have also been shown to induce less weight gain a significant concern for both patients and providers. The use of long-acting basal insulins may also reduce intrapatient variability in fasting blood glucose values. Moreover, the long-acting basal insulins such as glargine and detemir can be administered QD, which may enhance the potential for patient compliance. Aggressive titration of insulin doses based on a target fasting plasma glucose level of 100 to 120 mg/dL is essential to achieving target A1C levels (<7.0%,). As β-cell function declines, patients may require switch to basal-bolus insulin therapy. Although the long- and intermediate-acting insulin formulations are comparable with regard to efficacy as the basal component in basal-bolus therapy, the long-acting insulins have been associated with lower rates of nocturnal hypoglycemia, which can have a positive effect on glycemic control during the daytime. Conclusion: Basal insulins, both intermediate- and long-acting formulations, are playing an increasingly important role in the treatment of type 2 DM.

Intensivierte Insulintherapie des Typ-2-Diabetes mellitus: Prä- oder postprandiale Injektion von Aspart-Insulin?

Intensified insulin therapy using rapid acting insulin analogues is advocated in younger type 2 diabetic patients at risk of developing diabetic complications. Most patients prefer postprandial insulin injections. So far, however, there were no data on glycemic control by postprandial aspart insulin in patients with type 2 diabetes. To compare blood glucose responsiveness to preprandial vs. postprandial aspart injections, a randomised open intraindividual cross-over trial was carried out. Blood glucose was measured before and one hour after the three main meals and at bedtime. 18 insulin-naive patients with type 2 diabetes (age, 60 +/- 3 years (mean +/- SEM), known duration of the disease, 7 +/- 2 years) participated at this study. Both with preprandial and postprandial injections of aspart insulin, the averages of the 7-point blood glucose profiles (8.27 +/- 0.50 vs. 8.5 +/- 0.61 mmol/l) were similar. With postprandial aspart insulin, however, 84 % of the blood glucose levels measured one hour after breakfast exceeded > 10 mmol/l in comparison to 38 % with preprandial aspart insulin (p < 0.05). Patients injected similar amounts of basal and aspart insulin on both experimental days (insulin glargin, 11 +/- 3 U, aspart insulin, 23 +/- 2 vs. 25 +/- 2 U/day, p = 0.4843). Both preprandial and postprandial insulin aspart can be allowed to well-controlled type 2 diabetic patients. However, patients will benefit from the recommendation to inject insulin aspart immediately before meal if food with a high glycemic index such as the continental breakfast is to be consumed.

Initiating Insulin Therapy in Type 2 Diabetes

Safety and efficacy of biphasic insulin aspart 70/30 (BIAsp 70/30, prebreakfast and presupper) were compared with once-daily insulin glargine in type 2 diabetic subjects inadequately controlled on oral antidiabetic drugs (OADs). This 28-week parallel-group study randomized 233 insulin-naive patients with HbA(1c) values >/=8.0% on >1,000 mg/day metformin alone or in combination with other OADs. Metformin was adjusted up to 2,550 mg/day before insulin therapy was initiated with 5-6 units BIAsp 70/30 twice daily or 10-12 units glargine at bedtime and titrated to target blood glucose (80-110 mg/dl) by algorithm-directed titration. A total of 209 subjects completed the study. At study end, the mean HbA(1c) value was lower in the BIAsp 70/30 group than in the glargine group (6.91 +/- 1.17 vs. 7.41 +/- 1.24%, P < 0.01). The HbA(1c) reduction was greater in the BIAsp 70/30 group than in the glargine group (-2.79 +/- 0.11 vs. -2.36 +/- 0.11%, respectively; P < 0.01), especially for subjects with baseline HbA(1c) >8.5% (-3.13 +/- 1.63 vs. -2.60 +/- 1.50%, respectively; P < 0.05). More BIAsp 70/30-treated subjects reached target HbA(1c) values than glargine-treated subjects (HbA(1c) </=6.5%: 42 vs. 28%, P < 0.05; HbA(1c) <7.0%: 66 vs. 40%, P < 0.001). Minor hypoglycemia (episodes/year) was greater in the BIAsp 70/30 group than in the glargine group (3.4 +/- 6.6 and 0.7 +/- 2.0, respectively; P < 0.05). Weight gain and daily insulin dose at study end were greater for BIAsp 70/30-treated subjects than for glargine-treated subjects (weight gain: 5.4 +/- 4.8 vs. 3.5 +/- 4.5 kg, P < 0.01; insulin dose: 78.5 +/- 39.5 and 51.3 +/- 26.7 units/day, respectively). In subjects with type 2 diabetes poorly controlled on OADs, initiating insulin therapy with twice-daily BIAsp 70/30 was more effective in achieving HbA(1c) targets than once-daily glargine, especially in subjects with HbA(1c) >8.5%.

What's So Tough About Taking Insulin? Addressing the Problem of Psychological Insulin Resistance in Type 2 Diabetes

P atients with type 2 diabetes are often reluctant to begin insulin and, in many cases, delay the start of insulin therapy for quite lengthy periods of time. Patients may refuse insulin outright (“Look, doc, there is just no way I could take the needle.”), bargain with their health care providers for more time (“Please, I just need a few more months to see if I can drop this weight.”), or even drop out of treatment altogether. Sadly, actions such as these can lead to chronically elevated blood glucose levels, possibly for considerable periods of time, raising the risk for long-term complications. But what do we really know about such cases of “psychological insulin resistance” (PIR)? How often do they occur, why do patients harbor such powerful misgivings, and how can busy clinicians respond most effectively? While clinical lore suggests that PIR is quite common, there has been little formal study in this area. In the United Kingdom Prospective Diabetes Study (UKPDS),1 of those type 2 patients randomized to insulin therapy, 27% initially refused. Early reports from the international Diabetes Attitudes, Wishes, and Needs (DAWN) study2 indicate that the majority (54.9%) of insulin-naive patients worry about the possibility of insulin therapy. Okazaki et al.3 reported that 73% of type 2 patients beginning a diabetes education program where insulin was to be started were reluctant to do so at first. Finally, in a recent survey of insulin-naive type 2 patients,4 24.7% of respondents reported being not willing to take insulin if it was prescribed. Furthermore, the survey showed that Hispanic patients were much more frequently unwilling than non-Hispanic whites (55.6 vs. 21.5%). Qualitative data from Hunt et al.5 also suggest that PIR may be common in the Hispanic population. Overall, these data suggest that PIR may …

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.

PDB15: DOES PATIENT EXPERIENCE MATTER? TYPE II DIABETES PATIENTS' STATED PREFERENCES FOR INSULIN THERAPIES

OBJECTIVES: Patient preferences for alternative treatments may be affected by health status and experience with the treatment. Randomized Clinical Trials (RCTs) offer a unique opportunity to collect preference data while controlling for patient experience. METHODS: Patients with Type II diabetes in a large US RCT answered a series of stated preference (conjoint format) questions regarding attributes of alternative insulin therapies. All patients are insulin-naive and take insulin as part of the trial. Preference data is collected before the patient begins insulin, after 3 months, and after 6 months of insulin therapy. Insulin attributes include the frequency of insulin injections, method of injection (syringe or pen), glucose control and frequency of hypoglycemia. Personal health data such as glucose control are collected at each administration of the stated preference survey. RESULTS: Preferences are analyzed in an ordered probit panel model that controls for individual health status. Insulin administration attributes have the largest importance scores. The importance score of the insulin injection frequency attribute decreases during the later observation points. While few patients experience nighttime hypoglycemia, this attribute is significant and has a larger importance score than glucose control. CONCLUSIONS: Patient experience significantly affects patient preferences and the derived pharmacoeconomic measures and should be controlled in preference experiments. Results suggest that some insulin-naive patients are more averse to insulin injections before they begin insulin therapy. Results also suggest that increased experience with diabetes control measures during the trial affects treatment preferences.

Islet Cell Antibodies and Insulin Autoantibodies in Patients Treated with Oral Hypoglycaemic Agents

Clinical and immunological features suggesting Type 1 diabetes were assessed in 202 patients treated with oral hypoglycaemic agents for presumed Type 2 diabetes. Islet cell antibodies (ICA) were detected at a level exceeding 5 JDF units in 5.9% of patients, and complement-fixing ICA were detected in 3.4%. IgG insulin autoantibodies were detected in 8.8% of insulin-naive patients, none of whom were ICA positive. ICA were detected more frequently in patients with shorter duration of diabetes (p = 0.02). Age and relative body weight were similar in ICA positive and negative groups. ICA positive patients were more likely to have lost weight (p less than 0.02) than ICA negative patients, although this may have been attributable to the differing duration of diabetes in the two groups. Other individual clinical features suggesting Type 1 diabetes were not significantly more frequent in ICA positive patients. However, a higher proportion of ICA positive than ICA negative patients had one or more features suggestive of Type 1 diabetes irrespective of the duration of diabetes. Clinical features suggesting Type 2 diabetes were present in a similar proportion of ICA positive and ICA negative patients. Fasting and glucagon stimulated C-peptide levels were similar in ICA positive and matched ICA negative patients.

Comparison of Liquid Phase Radiobinding Assay and Solid Phase ELISA for the Measurement of Insulin Antibodies and Insulin Autoantibodies in Serum

Sera containing insulin antibodies from 20 insulin-treated diabetic patients, sera containing insulin autoantibodies from 20 insulin-naive non-diabetic patients, and from 10 normal controls, were tested at 1:20 dilution in three different radioimmunoassays (RIA) and an enzyme linked immunosorbent assay (ELISA), using a highly purified human insulin ligand. The RIA using insulin radiolabelled at multiple sites detected insulin antibodies in 17/20 and insulin autoantibodies in 13/20 sera. The same RIA using A-14-monoiodinated insulin was sensitive to antibodies and autoantibodies in all the sera. The same RIA using sera after insulin extraction detected only 13/20 diabetic sera and 9/20 autoimmune sera as positive, owing to a substantial rise in non-specific binding of the control sera. ELISA was sensitive to insulin antibodies and autoantibodies in every case. When binding curves for ELISA and the most sensitive RIA were compared using serial dilutions of four insulin antibody containing sera and four insulin autoantibody containing sera, antibody titres varied from 1.1 to 3.8 times higher in ELISA, and autoantibody titres from 10.6 to 28.6 times higher in ELISA. These studies indicate that ELISA is more sensitive than RIA to insulin antibodies, and in particular to insulin autoantibodies.

Magnetostrictive generation of surface elastic waves. (generation of surface waves at 60MHz by magnetostrictive coupling in yttrium iron garnet): Voltmer, F.W., White, R.M., Turner, C.W., Applied physics letters, vol 15, no 5 (1 September 1969), pp 153 (1920)

Objectives: The goal of this study was to compare daily insulin use, glycemic control, and health care costs in insulin-naive patients with type 2 diabetes who initiated treatment with either insulin detemir or insulin glargine.Methods: This was a retrospective cohort analysis of health care claims data and laboratory results for adult, insulin-naive patients with type 2 diabetes who were enrolled in a large US managed care organization and initiated basal therapy with insulin detemir or insulin glargine between May 1, 2006, and December 31, 2006. The daily average consumption (DACON) of insulin was calculated as the total number of units dispensed (excluding the last fill) divided by the number of days between the index date and the date of the last fill of the index insulin. Glycemic control was evaluated by comparing mean glycosylated hemoglobin (HbA1c) values in the preindex period (the 180 days before the index date) and the follow-up period (the 180 days after the index date). Mean all-cause and diabetes-related health care costs in the preindex and follow-up periods were calculated and compared.Results: The analysis included 48 patients initiating therapy with insulin detemir and 258 initiating therapy with insulin glargine. The mean age of the 2 cohorts was ~54 years, and most patients in each cohort were male (52.1% and 59.7%, respectively). Few patients in either cohort had a baseline HbA1c value <7% (13% and 10%), suggesting poor glycemic control at the time of insulin initiation. After adjustment for confounders (eg, preindex diabetes medication), the DACON of insulin was comparable between cohorts (29.3 and 29.6 U/d; P = NS), as were follow-up HbA1c values (8.2% and 7.9%). Insulin detemir and insulin glargine also were associated with comparable mean adjusted all-cause pharmacy costs ($3074 and $2899), medical costs ($2319 and $3704), and total health care costs ($6014 and $7023). However, insulin glargine was associated with significantly higher mean adjusted diabetes-related medical costs compared with insulin detemir ($1510 vs $707, respectively; P = 0.03), as well as significantly higher mean adjusted total diabetes-related health care costs ($3408 vs $2261; P = 0.03).Conclusions: In this managed care population of insulin-naive patients who initiated therapy with insulin detemir or insulin glargine, the daily insulin dose and glycemic control did not differ significantly between the 2 insulins. However, patients receiving insulin detemir incurred lower diabetes-related medical and total health care costs.

Piezo-electric crystal manufacturing apparatus and method (for location of atomic planes relative crystal surface): Samuelson, W.H., US patent 3, 448, 265 (3 June 1969) (filed 1 June 1966) (1910)

Objectives: The goal of this study was to compare daily insulin use, glycemic control, and health care costs in insulin-naive patients with type 2 diabetes who initiated treatment with either insulin detemir or insulin glargine.Methods: This was a retrospective cohort analysis of health care claims data and laboratory results for adult, insulin-naive patients with type 2 diabetes who were enrolled in a large US managed care organization and initiated basal therapy with insulin detemir or insulin glargine between May 1, 2006, and December 31, 2006. The daily average consumption (DACON) of insulin was calculated as the total number of units dispensed (excluding the last fill) divided by the number of days between the index date and the date of the last fill of the index insulin. Glycemic control was evaluated by comparing mean glycosylated hemoglobin (HbA1c) values in the preindex period (the 180 days before the index date) and the follow-up period (the 180 days after the index date). Mean all-cause and diabetes-related health care costs in the preindex and follow-up periods were calculated and compared.Results: The analysis included 48 patients initiating therapy with insulin detemir and 258 initiating therapy with insulin glargine. The mean age of the 2 cohorts was ~54 years, and most patients in each cohort were male (52.1% and 59.7%, respectively). Few patients in either cohort had a baseline HbA1c value <7% (13% and 10%), suggesting poor glycemic control at the time of insulin initiation. After adjustment for confounders (eg, preindex diabetes medication), the DACON of insulin was comparable between cohorts (29.3 and 29.6 U/d; P = NS), as were follow-up HbA1c values (8.2% and 7.9%). Insulin detemir and insulin glargine also were associated with comparable mean adjusted all-cause pharmacy costs ($3074 and $2899), medical costs ($2319 and $3704), and total health care costs ($6014 and $7023). However, insulin glargine was associated with significantly higher mean adjusted diabetes-related medical costs compared with insulin detemir ($1510 vs $707, respectively; P = 0.03), as well as significantly higher mean adjusted total diabetes-related health care costs ($3408 vs $2261; P = 0.03).Conclusions: In this managed care population of insulin-naive patients who initiated therapy with insulin detemir or insulin glargine, the daily insulin dose and glycemic control did not differ significantly between the 2 insulins. However, patients receiving insulin detemir incurred lower diabetes-related medical and total health care costs.