Multiple Daily Insulin Regimen Research Articles

ODP257 Alpelisib Treatment Associated With Severe Diabetic Ketoacidosis in a Patient With Metastatic Breast Cancer

Abstract Introduction Alpelisib is an inhibitor of phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) which was approved by US FDA to treat postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer. PIK3CA signaling is important for the metabolic actions of insulin and inhibition of PIK3CA was associated with hyperglycemia and rarely, ketoacidosis. Case Presentation An 82-year-old female patient with medical issues of metastatic breast cancer with recent progression started on Alpelisib one month before presentation. The patient was brought to the emergency department due to altered mental status and seizure on the same day of the presentation. She was tachycardic to 141 beats per minute and tachypneic to 22 breaths per minute. Physical exam was significant for encephalopathy and a right firm and indurated breast. Initial lab tests revealed leukocytosis to 13.1K/ uL, Blood glucose: 1124 mg/dl, Bicarbonate: 13, anion gap of 45, positive urine ketones, calculated Serum Osmolality: 386 mOsm/kg, HbA1c: 9.1, elevated corrected sodium to 147 mEq/L and elevated creatinine to 3.26 mg/dl from baseline of 0.61 mg/dl. Brain imaging including CT, MRI and MRA without acute findings. Infectious and ischemic workup were negative. She was admitted to neurocritical care as a case of new onset status epilepticus and new-onset diabetes complicated by severe Diabetic Ketoacidosis (DKA) treated with intravenous insulin drip, intravenous fluids and electrolytes replacement. During her admission, Alpelisib was held. The patient improved during the course of hospitalization with resolution of encephalopathy and ketoacidosis by the second day of hospitalization. She was transitioned from insulin infusion to multiple subcutaneous daily insulin regimen and her blood glucose readings remained controlled. Her oncologist was following and decided to stop Alpelisib and to proceed with palliative treatment until further evaluation as an outpatient. Patient was discharged home on multiple daily insulin regimen with outpatient follow ups with endocrinology and oncology. Discussion PIK3CA is the most commonly mutated gene in HR+/HER2- advanced or metastatic breast cancer and it is an indicator of poor prognosis. PIK3CA signaling is also important for the metabolic actions of insulin. Alpelisib is an inhibitor of PIK3CA. The SOLAR-1 trial, a phase 3 randomized clinical trial, showed significantly prolonged progression- free survival in patients whose tumors had a PIK3CA mutation treated with Alpelisib. However, hyperglycemia including severe ketoacidosis were also noted. Hyperglycemia was reported in 65% and ketoacidosis was reported in 0.7% of patients treated with Alpelisib. Alpelisib-induced DKA is a rare, but life-threatening, adverse event. There have been few reported cases in the literature. We want to emphasize the importance of screening, monitoring and intensifying treatment of patients with hyperglycemia who are on Alpelisib treatment. Presentation: No date and time listed

Partial remission in children and adolescents with type 1 diabetes: an analysis based on the insulin dose-adjusted hemoglobin A1c

Most patients with type 1 diabetes (T1D) experience a transient phase of partial remission (PR). This study aimed to identify the demographic and clinical factors associated with PR. This was a longitudinal retrospective cohort study of 133 children and adolescents with T1D. PR was defined by the gold standard insulin dose-adjusted hemoglobin A1c (HbA1c) (IDAA1c) of≤9. Remission was observed in 77 (57.9%) patients. At diagnosis, remitters had significantly higher pH (7.3±0.12 vs. 7.23±0.15, p=0.003), higher C-peptide levels (0.45±0.31ng/mL vs. 0.3±0.22, p=0.003), and they were significantly older (9.3±3.6 years vs. 7.3±4.2, p=0.008) compared with non-remitters. PR developed more frequently in patients without diabetic ketoacidosis (DKA) (p=0.026) and with disease onset after age 5 (p=0.001). Patients using multiple daily insulin regimen were more likely to experience PR than those treated with a twice daily regimen (63.9 vs. 32%, p=0.004). Only age at onset was an independent predictor of PR (OR: 1.12, 95% CI: 1-1.25; p=0.044). Remitters had lower HbA1c levels and daily insulin requirement from diagnosis until one year after diagnosis (p<0.001). PR recurred in 7 (9%) patients. The daily insulin requirement at three months was lower in remitters with PR recurrence compared to those without (0.23±0.14 vs. 0.4±0.17 U/kg/day, p=0.014). Addressing factors associated with the occurrence of PR could provide a better comprehension of metabolic control in T1D. The lack of DKA and higher C-peptide levels may influence PR, but the main factor associated with PR presence was older age at onset. PR may recur in a small proportion of patients.

Near-Normoglycemia, with Meaningful Discontinuations of Prandial Insulin, by Adding Weekly Albiglutide (Albi) to Uncontrolled Basal/Bolus Insulin-Treated Type 2 Diabetes (T2DM)

The glycemic efficacy of weekly Albi 50 mg to replace prandial insulin lispro (Lis) was evaluated in T2DM inadequately controlled on a multiple daily insulin regimen (≥3 injections/day). Basal/bolus insulin was optimized during a 4 week run-in phase before randomization to: 1) Albi + optimized insulin glargine (Gla), with prandial Lis subsequently discontinued by week 4 (n = 402) or 2) optimized Lis + optimized Gla (n = 412). At 26 week, the LS mean ± SE change from baseline in HbA1c was −1.04 ± 0.04 vs. −1.10 ± 0.04% (treatment difference 0.[95% CI, −0.05, 0.17]%; non-inferiority p &amp;lt;0.0001) (Table). In the Albi + Gla group, 218 subjects (54%) replaced all prandial insulin without reintroducing Lis through to 26 week, resulting in a total daily insulin dose reduction of 61 U. Mean number of injections was reduced from 29 to 13 (mean change ± SD: −16 ± 8) per week. GI adverse events were higher in the Albi group (26% vs. 13%). Albi + Gla was favorable for severe or documented symptomatic hypoglycemia (n: 230 [57%] vs. 309 [75%]) and weight change (LS mean ± SE: −2.0 ± 0.2 vs. +2.4 ± 0.2 kg; p&amp;lt;0.0001) vs. Lis + Gla. In conclusion, Albi meaningfully improved glucose control; prandial insulin was stopped in 54% of participants, allowing substantial reductions in insulin dose and number of injections, less hypoglycemia, and body weight loss. Disclosure J. Rosenstock: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Consultant; Self; Sanofi. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Merck &amp; Co., Inc., Pfizer Inc., Sanofi, Novo Nordisk Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Intarcia Therapeutics, Inc., Genentech, Inc. A.J. Nino: Employee; Self; GlaxoSmithKline plc.. Stock/Shareholder; Self; GlaxoSmithKline plc. J. Soffer: Employee; Self; GlaxoSmithKline plc.. Other Relationship; Self; GlaxoSmithKline plc.. J.M. Mallory: None. L.M. Erskine: Employee; Self; GlaxoSmithKline plc.. Stock/Shareholder; Self; GlaxoSmithKline plc. A. Acusta: Employee; Self; GlaxoSmithKline plc. J.F. Dole: Employee; Self; GlaxoSmithKline plc. M. Carr: Employee; Self; GlaxoSmithKline plc. P. Home: Consultant; Self; AstraZeneca. Other Relationship; Self; Biocon, Boehringer Ingelheim GmbH. Research Support; Self; GlaxoSmithKline plc.. Consultant; Self; Hanmi Pharmaceutical. Other Relationship; Self; Janssen Research &amp; Development. Consultant; Self; Janssen Research &amp; Development, Merck &amp; Co., Inc.. Other Relationship; Self; Merck &amp; Co., Inc.. Research Support; Self; Merck &amp; Co., Inc.. Other Relationship; Self; Novo Nordisk A/S. Consultant; Self; AntriaBio, Inc., Earlysign, Roche Diabetes Care Health and Digital Solutions. Research Support; Self; Sanofi. Consultant; Self; Sanofi.

Institution of Multiple Daily Insulin Regimen Compared with Twice Daily Pre-Mixed Insulin Regimen for Children with Type 1 Diabetes Mellitus

Children and young adults with type 1 diabetes mellitus are usually commenced on either a multiple daily insulin (MDI) regimen or twice daily pre-mixed insulin regimen at diagnosis. The MDI regimen is thought to more closely mimic the normal secretory patterns of endogenous insulin production to improve glycaemic control compared to twice daily or thrice-daily insulin regimens. This study aims to look at the effect on glycaemic control and growth over an 18-month period in children with type 1 diabetes mellitus on a twice-daily pre-mixed bis die (BD) insulin therapy compared to MDI regimen. This is a retrospective study comparing glycaemic control (HbA1c) and growth parameters (height SDS, weight SDS and BMI SDS) at intervals over an 18-month period between children with type 1 diabetes mellitus started on a twice-daily pre-mixed insulin regimen compared to those children started on MDI regimen. No significant difference was found between the two groups. Multiple regression analysis examining independent variables (age at diagnosis, insulin regimen, gender) affecting HbA1c values at 3, 6, 12 and 18 months confirmed that there were no independent factors affecting glycaemic control at any time point A twice-daily insulin regimen and an MDI insulin regimen were equivocal in efficacy of HBA1c control and measures of growth parameters within an 18-month period in paediatric diabetic patients with type 1 diabetes mellitus. Future prospective studies are warranted to address the issues described.

Basalog® is similar to Lantus® in producing glycemic control in patients with type 1 diabetes mellitus on multiple daily insulin regimens

This study was performed to compare the insulin glargine produced by two different manufacturers. The study determines the efficacy and safety of a new insulin glargine (Basalog®) having the same amino-acid sequence as Lantus® in patients with type 1 diabetes mellitus on multiple daily insulin regimen. After a run-in period of 4 weeks on once-daily Lantus®, patients were randomized in 1:1 ratio to receive once-daily treatment with either Basalog® (n = 107) or Lantus® (n = 108) for 12 weeks in this open-label multicenter study. Patients were enrolled from 15 hospitals in India. Change in HbA1c was the primary efficacy parameter; FPG, 7-point glucose profile and PPG were the secondary efficacy parameters. Hypoglycemia and immunogenicity were the main safety parameters. This was a non-inferiority study where non-inferiority could be claimed if mean difference (including 95% CI) was less than or equal to 0.5% for the primary efficacy parameter HbA1c. There was no statistically significant difference between the groups with respect to change in HbA1c (p = 0.69), FPG (p = 0.25) or PPG (p = 0.68). The change in HbA1c from baseline to end-point was 7.86 ± 1.11 to 7.80 ± 1.24% in Basalog® treated patients and 7.76 ± 1.17 to 7.58 ± 1.27% in Lantus® treated patients. Proportion of patients achieving HbA1c <7% was also comparable (40.48% in Basalog® vs 38.30% in Lantus®). The nature and frequency of adverse events, percentage of patients positive for anti-insulin glargine antibodies were similar in both groups. Forty-three (40.19%) subjects on Basalog® experienced at least one hypoglycaemic event, while 45 (41.67%) subjects on Lantus® experienced the same. Basalog® was found to have similar efficacy and safety as Lantus® in treatment of patients with type 1 diabetes mellitus.

Overweight, obesity and features of metabolic syndrome in children with diabetes treated with insulin pump therapy

There has been no specific evaluation of atherogenic risk factors in children with type 1 diabetes mellitus (T1DM) treated with continuous subcutaneous insulin infusion (CSII). We, therefore, studied the prevalence of overweight/obesity and metabolic syndrome among these patients. Five hundred children with T1DM treated with CSII and multiple daily insulin (MDI) regimen were included in the study. Anthropometric data/physical examination, data concerning diabetes, and a lipid profile were assessed in this group, and compared with respect to treatment method (CSII vs. MDI). Almost one-third (30.2%) of the children were overweight/obese. The body mass index (BMI) values at the time of the present evaluation were significantly higher in comparison with the BMI values 3-6 months after the diagnosis. Dyslipidemia was recognized in 51.6%, hypertension in 4.8%, and the metabolic syndrome in 3.2%. of the subjects. The overweight/obese children differed from their normal-weight counterparts with respect to metabolic control, the incidence of hypertension, dyslipidemia, and metabolic syndrome. The girls showed higher prevalence of overweight/obesity and higher BMI values compared to the boys. The children treated with CSII had the same prevalence of overweight/obesity, but a lower incidence of dyslipidemia, and a better metabolic control compared to the children treated with MDI regimen. Our study shows a high prevalence of overweight/obesity and dyslipidemia in children with T1DM including those treated with an insulin pump.

Insulin treatment of Type 2 diabetes: a clinical perspective

Some copies of this issue of the Journal of Diabetes are being distributed in China with a reprint describing the findings of a consensus conference organized by NovoNordisk on how best to use the combination of 30% insulin aspart (rapid-acting) and 70% protamine-based (intermediate-acting) insulin (BIAsp 30).1 The article offers guidance in approaches to intensifying treatment with this form of insulin, but does not compare BIAsp 30 with other insulin treatment regimens, particularly for people with Type 2 diabetes, a most interesting and important topic. It is not widely appreciated that the UK Prospective Diabetes Study (UKPDS) presented evidence that Type 2 diabetic people receiving either of the sulfonylureas (SU) used for initial treatment had progressively increasing need for addition of insulin over time, with nearly 10% needing this treatment after 1 year, and a linear increase to approximately half requiring this by 6 years.2 Insulin alone was inferior to combined treatment with insulin + SU in maintaining glycemic control.2 Although one may argue that in the current era of the availability of multiple oral agents the use of insulin is less necessary, comparison of maximal dose metformin and pioglitazone plus titrated SU treatment versus metformin plus BIAsp 30 showed that although either approach could successfully maintain excellent glycemic control, the former led to both a greater increase in weight and an increasing frequency of hypoglycemia.3 Therefore, insulin plus oral agents may be a preferable approach to thiazolidinedione/SU/metformin combinations for many Type 2 diabetic people. Multiple approaches have been shown to be effective with insulin treatment. The rapid-acting insulin analogs lispro, aspart, and glulisine lead to more physiologic replication of the normal postprandial insulin secretory pattern,4 with a reduction in postprandial glycemia.5-7 The use of such analogs in combination with a protamine-containing intermediate-acting insulins led to the development of BIAsp 30 and to the similar Eli Lilly product, namely protamine-lispro 75%/lispro 25% (BI-lispro 25), both of which have the advantage over both intermediate-acting insulin alone and combinations of regular human insulin plus intermediate-acting insulin of better reducing postprandial glycemia8, 9 while maintaining benefit in overnight glucose-lowering.10 Furthermore, these preparations have greater simplicity of administration, with the potential for a reduced number of injections. However, one problem with all such protamine-containing insulin preparations is their pronounced peak effect, often occurring at an undesirable time after evening administration,11 so that although effective in improving glycemia, many studies suggest that they do so at the expense of a greater likelihood of nocturnal hypoglycemia than seen with the ‘peakless’ insulin analogs detemir and glargine.12 (It should be noted that not all authors have reported this finding.13) Furthermore, intermediate-acting insulin given alone may not be quite as effective as insulin glargine in lowering A1c.14 Detemir appears to have less variability in overnight glucose-lowering action than seen either with protamine–intermediate-acting insulin or with insulin glargine,15 with studies comparing it with intermediate-acting insulin showing lesser degrees of weight gain.16 The question should then be asked, which is better: basal insulins, such as protamine-containing preparations, glargine, or detemir; bolus insulins, particularly the rapid-acting analogs lispro, aspart, and glulisine; or the combination insulin preparations BIAsp 30 and BI-lispro 25? This question was addressed by the Treating to Target in Type 2 Diabetes (4-T) study.17 A total of 708 Type 2 diabetic people were randomized to BIAsp 30, to aspart three times daily before meals, or to insulin detemir once or twice daily. At 1 year, the detemir group had a lesser improvement in A1c but less weight gain, less hypoglycemia, and a lower total daily insulin dose. After 3 years, when all patients were moved to a multiple daily insulin (MDI) approach, hypoglycemia rates remained significantly lower in those started on insulin detemir and, in addition, these patients continued to exhibit less weight gain even though the glycemic improvement was now similar across all groups. Furthermore, cardiovascular mortality was significantly lower in the group started on basal insulin initially and significantly more serious adverse events occurred in those people initially randomized to BIAsp 30.18 This context should be used in interpreting the consensus statement of Unnikrishnan et al.1 regarding intensification of insulin therapy with BIAsp 30. The authors appropriately suggest that this preparation, dosed up to three-times daily, may allow improved glycemic control over basal insulin preparations and present evidence supporting this concept. Although requiring considerable effort on the parts of both the clinician and the diabetic patient, initial use of basal insulin titrated to complex basal-bolus MDI regimens may be preferable to multiple doses of either BIAsp 30 or BI-Lispro 25, so that one should strongly consider MDI as the optimal treatment for management of insulin-requiring patients with Type 2 or Type 1 diabetes.

Long-term Effect of Combination Therapy with Mitiglinide and Once Daily Insulin Glargine in Patients who were Successfully Switched from Intensive Insulin Therapy in Short-term Study

We have previously reported the therapeutic efficacy of mitiglinide combined with once daily insulin glargine (mitiglinide regimen) after switching from multiple daily insulin regimen of aspart insulin and glargine (intensive insulin regimen) in inpatients with type 2 diabetes mellitus in two consecutive days. In the present study, we followed up 9 of the 15 responsive patients with these novel regimens for 6 months after discharge. The data collected from these patients were compared to those of 15 randomly chosen patients who had well matched background and received intensive insulin regimen during hospitalization which was continued after discharge. The average HbA1c level of these 9 patients with mitiglinide regimen at 6 months was 6.7 +/- 0.8% and was comparable to that of the patients with intensive insulin regimen (HbA1c = 7.0 +/- 1.0%). In conclusion, mitiglinide and insulin glargine combination therapy maintained fair glycemic control for as long as 6 months in subpopulation of Japanese patients with type 2 diabetes.

Premeal Insulin Treatment During Basal-Bolus Regimen in Young Children With Type 1 Diabetes

The introduction of insulin analogs in clinical practice suggests updating therapeutic schemes in subjects with type 1 diabetes. We read with interest the recent article by Alemzadeh et al. (1), which was designed to determine the feasibility of a flexible multiple daily insulin regimen in preschool children. Rapid-acting insulin analogs offer unquestionable advantages due to their pharmacokinetics and pharmacodynamic properties. However, when used in a basal-bolus regimen, they also need great accuracy in determining the carbohydrate content of the meal. A small mistake could generate a significant problem, including hyperglycemia or hypoglycemia. The meal carbohydrate count system seems to be effective and safe in controlling postmeal hyperglycemia in children treated with continuous subcutaneous insulin infusion (2), but when rapid-acting analogs are associated with glargine at bedtime, they could leave a “window” of low plasma insulin levels during the first portion of the night. Indeed, glargine-insulin plasma levels could not yet be consistently stable (3). Moreover, when using rapid-acting insulin analogs, children need an additional insulin shot to control the carbohydrate intake of their afternoon snack, which is a common practice among children living in the Mediterranean area. The object of the present study was to evaluate fasting and postmeal metabolic effects in prepuberal children treated with glargine and regular or rapid-acting insulin using the carbohydrate counting system. We recruited 30 prepuberal children aged 8.1 ± 1.8 years (means ± SD) with type 1 diabetes, having basal C-peptide <0.1 nmol/l, diabetes duration 5.2 ± …

An Integrated Graphic Scheme for the Display of Insulin Prescription and Blood Glucose Information

This study was undertaken to determine whether use of an integrated graphic scheme for the display of insulin prescription and blood glucose information has an impact on simulated decision-making in clinical practice. Five test cases representing patients treated with multiple daily insulin regimens were selected from a database of stored blood glucose readings. Five endocrinologists made treatment recommendations based on review of aggregated readings and corresponding insulin prescriptions. Twenty subjects were randomized to complete two sets of sequential real-time data management exercises. One set focused on evaluation of insulin prescriptions and readings printed as entries in logbooks. The other focused on evaluation of displays of insulin doses and readings plotted out according to an integrated graphic scheme of representation. Subjects were more likely to make correct decisions in four out of five test cases after reviewing displays. Subjects were less likely to make incorrect decisions in all of five test cases after reviewing displays. Completion times were 30-66% shorter for exercises involving review of displays. An integrated graphic scheme that associates representations of insulin doses with metaphor graphic displays of aggregated blood glucose readings may facilitate decisionmaking in clinical practice.

Therapeutic Efficacy of Mitiglinide Combined with Once Daily Insulin Glargine after Switching from Multiple Daily Insulin Regimen of Aspart Insulin and Glargine in Patients with Type 2 Diabetes Mellitus

Mitiglinide is novel class of rapid-acting insulin secretagogues, which have been widely used alone or in combination with other oral hypoglycemic drugs to improve postprandial hyperglycemia in early type 2 diabetes. While mitiglinide enhances postprandial requirement of insulin, the efficacy of mitiglinide combined with insulin has yet to be established. We investigated the efficacy of mitiglinide combined with insulin glargine, the first soluble insulin analog that has a flat and prolonged effect. After control with the intensive regimen (daily aspart insulin and glargine), 30 inpatients with type 2 diabetes were switched to premeal mitiglinide combined with once daily insulin glargine (mitiglinide regimen), and daily profiles of blood glucose level were compared under each regimen. Fifteen patients showed similar control of hyperglycemia with mitiglinide regimen and intensive insulin regimen, assessed by M value (<32), while the remaining 15 showed worsening under the mitiglinide regimen. The patients who were well controlled with mitiglinide regimen were significantly younger (51.9 +/- 16.0 years, p<0.005) and heavier (body mass index: 25.7 +/- 3.3 kg/m(2), p<0.05) than those who were not (67.9 +/- 8.7 and 23.0 +/- 3.1, respectively). Moreover, insulin doses of aspart per body weight were significantly fewer in effective group than in ineffective group. Duration of diabetes was shorter in the effective group, albeit insignificantly. Previous treatment before starting intensive insulin regimen, such as insulin and sulfonylurea, was not different between the two groups. Our results suggest that mitiglinide plus insulin glargine combination therapy is useful for lowering both fasting and postprandial hyperglycemia in a subpopulation of type 2 diabetes. The long-term effects of such treatment need to be established in future studies.

Continuous Subcutaneous Insulin Infusion and Multiple Dose of Insulin Regimen Display Similar Patterns of Blood Glucose Excursions in Pediatric Type 1 Diabetes

Continuous subcutaneous insulin infusion (CSII) is believed to decrease glycemic variability and clinical hypoglycemia compared with the multiple daily insulin (MDI) regimen. To compare the indices of glycemic instability between CSII and MDI, we analyzed the continuous glucose monitoring system (CGMS) (Medtronic MiniMed, Northridge, CA) profiles of a group of children with type 1 diabetes mellitus with history of frequent blood glucose (BG) fluctuations and hypoglycemia. Data from 14 (nine girls, five boys) patients (3.9-16.8 years old) on CSII and 14 age- and sex-matched (nine girls, five boys) patients (3.9-16.0 years old) on MDI with similar glycemic control (hemoglobin A1c: 7.9 +/- 1.0% vs. 7.9 +/- 1.5%) and body mass index (BMI) (20.1 +/- 4.3 vs. 19.9 +/- 4.1 kg/m(2)) were evaluated by the CGMS. Mean BG (MBG), absolute means of daily differences (MODD), mean amplitude of glycemic excursion (MAGE), and number of hypoglycemic events (BG <60 mg/dL) for 48 h were calculated. The MBG, MODD, MAGE, and number and mean duration of hypoglycemia events in the CSII group were similar to those in the MDI group. The MAGE had an inverse correlation with age (CSII: r (2) = 0.52, P = 0.003; MDI: r (2) = 0.29, P < 0.04) and BMI (CSII: r (2) = 0.38, P < 0.02; MDI: r (2) = 0.71, P < 0.0002). However, there was a positive relationship between MAGE and bolus:basal insulin ratio in the CSII (r (2) = 0.28, P < 0.05) and MDI (r (2) = 0.33, P < 0.03) groups. Also, the MAGE had a positive correlation with frequency of hypoglycemic events in the CSII (r (2) = 0.44, P < 0.01) and MDI (r (2) = 0.35, P < 0.03) groups. The CSII and MDI regimens in children and adolescents with comparable glycemic control displayed similar patterns of glycemic excursions, implying that factors influencing glycemic instability in pediatric type 1 diabetes mellitus appear to be independent of treatment modality.

Beneficial Effects of Continuous Subcutaneous Insulin Infusion and Flexible Multiple Daily Insulin Regimen Using Insulin Glargine in Type 1 Diabetes

The aim of this study was to evaluate the metabolic effects of continuous subcutaneous insulin infusion (CSII) with flexible multiple daily insulin (FMDI; premeal lispro + bedtime glargine) therapy as determined by glycosylated hemoglobin (HbA1c), body mass index (BMI), and hypoglycemic episodes in a group of patients who made the transition from multiple daily insulin (premeal lispro + bid ultralente) to either CSII or FMDI therapy. Data from 40 (27 female and 13 male) patients (10.1-17.8 years of age) who were on CSII and 40 age- and gender-matched (27 female and 13 male) patients (10.3-17.3 years of age) who were on FMDI were collected during regularly scheduled visits at a similar frequency over a 1-year period. The total daily insulin dose did not change in CSII (0.97 +/- 0.24 vs 0.91 +/- 0.22 U/kg) and FMDI (0.98 +/- 0.21 vs 0.97 +/- 0.21 U/kg) patients, whereas the bolus:basal insulin ratio was significantly increased in both CSII (1.01 +/- 0.43 vs 1.32 +/- 0.52) and FMDI (1.07 +/- 0.0.41 vs 1.29 +/- 0.47) patients. The total cohort of CSII patients showed a decrease in HbA1c from 8.4 +/- 1.0% to 7.8 +/- 0.8%, whereas the FMDI cohort did not show a significant change in HbA1c (8.5 +/- 1.1% to 8.2 +/- 0.9%). However, 40% of the CSII group and 22.5% of the FMDI group showed > or =1.0% improvement in HbA1c. Also, a similar number of patients in CSII (52.5%; 8.0 +/- 1.1 to 7.2 +/- 0.5%) and FMDI (47.5%; 8.0 +/- 0.5% to 7.5 +/- 0.4%) maintained or achieved target HbA1c values <8.0%. The BMI increased significantly in the CSII group (21.6 +/- 3.2 vs 23.0 +/- 3.0 kg/m2) but did not change in the FMDI group (21.9 +/- 3.9 vs 22.6 +/- 3.8 kg/m2). There was a significant reduction in the rate of severe hypoglycemia (events/100 patient-years) in both cohorts: 20.6 to 8.2 in the CSII and 18.8 to 7.5 in the FMDI. Similarly, the rate of moderate hypoglycemia decreased in both CSII (68.3-35.4) and FMDI (56.3-30.4). CSII therapy resulted in a significant improvement in HbA 1c in the entire group, whereas FMDI therapy improved HbA1c in only a subgroup of patients. However, almost half of the patients in each of the treatment groups maintained or achieved target glycemic control. Both CSII and FMDI treatment groups demonstrated a decreased rate of hypoglycemia without an abnormal increase in BMI. Although the design of this study does not allow direct comparison of the metabolic effects of CSII and FMDI therapies, both regimens seem to be superior to basal ultralente and lispro multiple daily insulin regimen and offer desirable therapeutic alternatives in pediatric diabetes care.

Current controversies in the mechanisms and treatment of gestational diabetes.

Gestational diabetes mellitus (GDM) is a heterogeneous entity, including carbohydrate intolerance of variable severity with onset or first recognition during pregnancy. Insulin resistance and beta-cell dysfunction are thought to be major determinants of its development. Its pathomechanism in many ways resembles that of type 2 diabetes. There is an evolving body of evidence from the last decade presenting similarities between gestational diabetes and the metabolic (insulin resistance) syndrome. These new observations suggest that GDM might be an early manifestation of the metabolic syndrome. The desired treatment target of GDM is normoglycemia. It can be reached by dietary treatment; however, if it fails, maternal glycemic monitoring or combined fetal-maternal monitoring, or even insulin (if required) can help reach it. Multiple daily insulin regimens are becoming more widely accepted for the treatment of GDM. Insulin analogues, however, need some more evidence to support their usefulness and safety during pregnancy. The screening for GDM, the reclassification, regular care, and follow-up of these women after pregnancy are of the utmost importance to delay or prevent not only type 2 diabetes but cardiovascular complications as well.

Increasing the use of intensified management of diabetes: An education program for physicians

Traditionally, continuing medical education (CME) programs do not address the changes in the organization of a practice necessary to implement new care strategies. We developed a continuing medical education program that included a structured method, termed environmental optimizing, to help primary care physicians implement intensified management strategies for insulin-requiring patients with diabetes mellitus. To evaluate this approach, 88 physicians and 126 of their non-obese, insulin-requiring patients were surveyed and interviewed pre-program and at six and twelve months post-program. The results suggest that this approach to CME resulted in a significant number of physicians adopting the program recommendations. Specifically, there was a significant increase in the use of: 1) multiple daily insulin regimens (p=.01), 2) a program-specific “tracer” insulin regimen (p=.001), 3) the use of HbAl assays to adjust insulin (p<.05), diet and exercise regimens (p<.05), and 4) patients' self monitoring behavior (p<.01). The results of this study suggest that incorporating environmental optimizing into CME curricula may enhance the adoption of program recommendations.