BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) and obesity is increasing in Korea. Clinical studies in patients with T2DM have shown that combining the glucagon-like peptide-1 receptor agonist exenatide twice daily with basal insulin is an effective glucose-lowering strategy. However, these studies were predominantly conducted in non-Asian populations. METHODS: We conducted a subgroup analysis of data from a multinational, 30-week, randomized, open-label trial to compare the effects of exenatide twice daily (n=10) or three times daily mealtime insulin lispro (n=13) among Korean patients with T2DM inadequately controlled (glycosylated hemoglobin [HbA1c] >7.0%) on metformin plus optimized insulin glargine. RESULTS: Exenatide twice daily and insulin lispro both reduced HbA1c (mean −1.5% and −1.0%, respectively; P<0.01 vs. baseline). Fasting glucose and weight numerically decreased with exenatide twice daily (−0.7 mmol/L and −0.7 kg, respectively) and numerically increased with insulin lispro (0.9 mmol/L and 1.0 kg, respectively). Minor hypoglycemia occurred in four patients receiving exenatide twice daily and three patients receiving insulin lispro. Gastrointestinal adverse events were the most common with exenatide twice daily treatment. CONCLUSION: This analysis found treatment with exenatide twice daily improved glycemic control without weight gain in Korean patients with T2DM unable to achieve glycemic control on metformin plus basal insulin.
Diabetes Mellitus, Type 2* ; Fasting ; Glucagon-Like Peptide-1 Receptor ; Glucose ; Humans ; Hypoglycemia ; Insulin Glargine ; Insulin Lispro* ; Insulin* ; Korea ; Meals ; Metformin ; Obesity ; Prevalence ; Weight Gain

Increased plasma insulin levels are often observed in exogenous insulin overdose patients. However, plasma insulin level may decrease with time. We report a case of low plasma insulin level hypoglycemia after insulin lispro overdose. The patient was a 37-year-old man with no previous medical history who suspected insulin lispro overdose. Upon arrival, his Glasgow coma scale was 3 points and his blood sugar level (BSL) was 24 mg/dl. We found five humalog-quick-pen (insulin lispro) in his bag. There was no elevation of glucose level, despite an initial 50 ml bolus of 50% glucose and 150 cc/hr of 10% dextrose continuous intravenous infusion. He also suffered from generalized tonic-clonic seizure, which was treated with lorazepam and phenytoin. We conducted endotracheal intubation, after which he was admitted to the intensive care unit (ICU). There were recurrent events of hypoglycemia below BSL<50 mg/dl after admission. We repeatedly infused 50 ml 50% glucose 10 times and administered 1 mg of glucagon two times. The plasma insulin level was 0.2 uU/ml on initial blood sampling and 0.2 uU/ml after 5 hours. After 13 hours, his BSL stabilized but his mental status had not recovered. Diffuse brain injury was observed upon magnetic resonance imaging (MRI) and severe diffuse cerebral dysfunction was found on electroencephalography (EEG). Despite 35 days of ICU care, he died from ventilator associated pneumonia.
Adult ; Blood Glucose ; Brain Injuries ; Electroencephalography ; Glasgow Coma Scale ; Glucagon ; Glucose ; Humans ; Hypoglycemia* ; Infusions, Intravenous ; Insulin Lispro* ; Insulin* ; Intensive Care Units ; Intubation, Intratracheal ; Lorazepam ; Magnetic Resonance Imaging ; Phenytoin ; Plasma* ; Pneumonia, Ventilator-Associated ; Seizures

INTRODUCTION: In the management of type 2 diabetes, insulin is often started late, when there is failure to achieve good control on maximum oral agents. Clinical inertia to insulin initiation and intensification is widely prevalent in our local setting resulting in poor control of diabetes. This study looked into a stepwise insulin combinations treatment algorithm used in an Endocrinology referral clinic at the University of Santo Tomas Hospital (USTH). It aimed to demonstrate the clinical course of the patients , determine the degree of HbA1c reduction, and show the associated extent of hypoglycemia and weight gain.

METHODS: This is a retrospective chart review of 104 patients that used the following stepwise treatment: Oral regimen; Regimen A: basal+oral; Regimen B: basal+premeal bolus TID±oral; Regimen C: premixed aspart 70/30 or lispro 75/25 TID or BID with prelunch bolus, ± oral; Regimen D: premixed 70/30 BID+premeal bolus TID ± oral; Regimen E: premixed 70/30 BI +premeal bolus TID+basal ±oral. All received automatic snacking two hours after main meals to prevent hypoglycemia. Patients were educated on proper diet and exercise. Data was analyzed using paired t-test, frequencies and percentages.

RESULTS: Most ended on the intensive insulin regimens D 57(55%), and E 18 (17%). Significant HbA1c reduction was demonstrated as follows: Regimen A (n=8):1.376±0.919 (p=0.000), Regimen B (n=18):2.320±2.177 (p=0.000), Regimen D (n=57):2.197±2.158 (p=0.000), Regimen E (n=18):2.684±1.689 (p =0.000). Overall mean weight gain was 1.070 ± 11.435 kg (p=0.335). Ten, nonsevere hypoglycemia events were reported.

CONCLUSION: The use of this stepwise insulin combinations treatment algorithm exerted significant HbA1c reduction, with minimal events of hypoglycemia, and statistically insignificant weight gain. Hence, this is a feasible tool that may be used as a guide for intensification of insulin treatment.

Human ; Male ; Female ; Aged ; Middle Aged ; Adult ; Insulin Lispro ; Insulin ; Diabetes Mellitus, Type 2 ; Regimen B ; Weight Gain ; Hypoglycemia ; Antineoplastic Combined Chemotherapy Protocols ; Diet ; Algorithms

Allergic reaction to insulin is uncommon since the introduction of human recombinant insulin preparations and is more rare in pregnant than non-pregnant females due to altered immune reaction during pregnancy. Herein, we report two cases of allergic reaction to insulin in gestational diabetes that were successfully managed. One case was a 33-year-old female using isophane-neutral protamine Hagedorn human insulin and insulin lispro. She experienced dyspnea, cough, urticaria and itching sensation at the sites of insulin injection immediately after insulin administration. We discontinued insulin therapy and started oral hypoglycemic agents with metformin and glibenclamide. The other case was a 32-year-old female using insulin lispro and insulin detemer. She experienced pruritus and burning sensation and multiple nodules at the sites of insulin injection. We changed the insulin from insulin lispro to insulin aspart. Assessments including immunoglobulin E (IgE), IgG, eosinophil, insulin antibody level and skin biopsy were performed. In the two cases, the symptoms were resolved after changing the insulin to oral agents or other insulin preparations. We report two cases of allergic reaction to human insulin in gestational diabetes due to its rarity.
Adult ; Biopsy ; Burns ; Cough ; Diabetes, Gestational* ; Dyspnea ; Eosinophils ; Female ; Glyburide ; Humans ; Hypersensitivity* ; Hypersensitivity, Immediate ; Hypoglycemic Agents ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Insulin Aspart ; Insulin Lispro ; Insulin* ; Metformin ; Pregnancy ; Pruritus ; Sensation ; Skin ; Urticaria

BACKGROUND: Diabetes mellitus (DM) is a major cause of morbidity and mortality in the Philippines. Improvement in hemoglobin A1c (HbA1c) remains below recommended targets for Filipino patients. Safe and effective therapies are needed for this population.
OBJECTIVE: To investigate treatment-emergent adverse events (TEAEs) and change in HbA1c among Filipino patients with DM treated with insulin lispro mix 25/75 in a real-world setting.
MATERIALS AND METHODS: This was a prospective, non-interventional, post-marketing surveillance study among 459 Filipinos aged 18 years or older with type 1 or 2 DM. Patients were treated with insulin lispro mix 25/75 according to the approved label, as prescribed by the investigators, and observed for 12 weeks. Occurrence of all TEAEs and change in HbA1c from baseline to final visit were reported.
RESULTS: Mean (SD) treatment duration was 12.93 (5.7) weeks, and mean total daily dose was 0.62 (0.29) units/kg. Eighteen patients (3.9%) experienced 23 TEAEs, the majority of which were mild. None were reported to be related to treatment. No serious TEAEs or hypoglycemic episodes were reported. Mean (95% confidence interval) HbA1c was significantly reduced by -2.03% (-2.19%, -1.87%), and 36.3% of patients achieved HbA1c <7.0% at 12 weeks.
CONCLUSION: In this observational study, no treatmentrelated safety signals using insulin lispro mix 25/75 were detected among Filipino diabetic patients. HbA1c was significantly reduced in Filipino patients with DM at 12 weeks.

Human ; Male ; Female ; Middle Aged ; Adult ; Insulin Lispro ; Hemoglobin A, Glycosylated ; Hypoglycemia ; Diabetes Mellitus ; Hypoglycemic Agents

BACKGROUND: The initial insulin dose is often determined by clinical experience or with a formula using the body weight. However, it may be difficult to determine the initial insulin dose because various factors such as insulin sensitivity and the glycemic status can influence the insulin requirement. The purpose of this study was to assess the factors that influence the initial insulin requirement in insulin naive patients with type 2 diabetes mellitus. METHODS: A total 128 patients who were admitted for glycemic control were investigated. The patients were managed with long-acting insulin glargine and rapid-acting insulin lispro. RESULTS: The basal insulin requirement was positively correlated with waist circumference, body mass index (BMI), the HbA1C, AST, ALT, fasting plasma glucose and 2-hour postprandial glucose levels and the homeostasis model assessment of insulin resistance (HOMA-IR), but it was negatively correlated with age and the stimulated C-peptide level. The daily insulin requirement was positively correlated with waist circumference, BMI, the HbA1C, AST, ALT, triglyceride, fasting plasma glucose and 2-hour postprandial glucose level and HOMA-IR, but it was negatively correlated with age. On the multiple linear regression analysis, the basal insulin requirement was independently associated with BMI (beta = 0.507, p < 0.001), the 2-hour postprandial glucose level (beta = 0.307, p < 0.001), the ALT level (beta = 0.214, P = 0.015) and the meal-stimulated C-peptide level (beta = -0.209, P = 0.010). The daily insulin requirement was independently associated with BMI (beta = 0.508, p < 0.001) and the 2-hour postprandial glucose level (beta = 0.404, p < 0.001). CONCLUSION: Our results show that the BMI and 2-hour postprandial glucose level are useful predictors of the initial insulin requirement in insulin naive type 2 diabetic patients. It may be prudent to consider the other various factors that influence the insulin requirement together when insulin therapy is required.
Body Mass Index ; Body Weight ; C-Peptide ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Homeostasis ; Humans ; Insulin ; Insulin Lispro ; Insulin Resistance ; Insulin, Long-Acting ; Insulin, Short-Acting ; Linear Models ; Plasma ; Waist Circumference ; Insulin Glargine

BACKGROUNDGlycemic control prevents onset and progression of diabetes-related long-term complications. The objective of this study was to demonstrate that twice daily insulin lispro low mix 25 is noninferior to twice daily human insulin mix 30/70 in achieving glycemic control as measured by hemoglobin A1c (HbA1c), from baseline to endpoint, in patients with type 1 or 2 diabetes.

METHODSIn this phase IV, crossover, open-label, multicenter study, 117 Chinese patients with diabetes were randomly assigned to one of two treatment sequence groups. One group received 12-week treatment with twice daily human insulin mix 30/70 followed by 12-week treatment with twice daily insulin lispro low mix 25, while the other group received the reverse treatment sequence. HbA1c, baseline-to-endpoint change in HbA1c, proportion of patients achieving target HbA1c insulin doses were measured for each period. Safety and tolerability were also assessed.

RESULTSA statistically significant reduction (P insulin mix 30/70: mean HbA1c = 7.91% (95%CI: 7.67%, 8.15%); insulin lispro low mix 25: mean HbA1c = 7.96% (95%CI: 7.72%, 8.20%)). The 95%CI (-0.20, 0.10) of the difference between the two treatments satisfied the prespecified noninferiority margin of 0.3% (lower limit of 95% CI > -0.3%). No statistically significant differences between treatments were observed for any of the secondary efficacy measures. The incidence of treatment-emergent adverse events and hypoglycemia between the two treatments and treatment sequence groups was similar. Three serious adverse events were reported (human insulin mix 30/70 group: 2 patients (1.7%, hypoglycemic coma and cardiac failure); insulin lispro low mix 25 group: 1 patient (0.9%, stroke)). All serious adverse events were resolved and no patients died during the study.

CONCLUSIONThe results support noninferiority of twice daily insulin lispro low mix 25 versus twice daily human insulin mix 30/70 in HbA1c control in Chinese patients with type 1 or 2 diabetes.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Diabetes Mellitus, Type 1 ; drug therapy ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; Drug Administration Schedule ; Female ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemic Agents ; administration & dosage ; Insulin ; administration & dosage ; analogs & derivatives ; Insulin Lispro ; Male ; Middle Aged ; Young Adult

PURPOSE: With long acting time of 24 hours and no peak concentration, insulin glargine (Lantus(R), Aventis Pharma, Frankfurt, Germany) is preferably used as basal insulin to control fasting glucose level. The study was undertaken to evaluate the effect of insulin glargine as a basal insulin of intensive insulin therapy in uncontrolled type 1 diabetic adolescent patients. METHODS: The subject included 47 uncontrolled type 1 diabetic patients who have been treated by NPH and RI or insulin lispro. They were followed up for the mean duration of 7.2 months. Clinical parameters including treatment duration, fasting plasma glucose, glycosylated hemoglobin, total insulin doses, body weight, and body mass index were analyzed and compared before and after introduction of insulin glargine therapy. Mean age was 16.0+/-2.8 years old. RESULTS: Glycosylated hemoglobin was significantly decreased (9.4+/-1.4% to 8.6+/-1.4%, P<0.001) and fasting blood glucose level was also significantly decreased (182.6+/-53.2 mg/dL to 129.1+/-52.3 mg/dL, P<0.001, n=18) after switching to insulin glargine. Body weight increased significantly (56.4+/-9.4 kg to 57.9+/-9.6 kg, P=0.022) but increment of both total insulin dose (1.03+/-0.32 unit/kg/day to 1.04+/-0.29 unit/kg/day) and body mass index were insignificant. The mean dose of insulin glargine was 0.42+/-0.13 unit/kg/day. CONCLUSION: Insulin glargine as a basal insulin of intensive insulin therapy is more efficacious in diabetic control in adolescents with uncontrolled type 1 diabetes mellitus than conventional insulin therapy. Long-term follow up is needed for evaluating the effect of insulin glargine on diabetic control, prevention of hypoglycemia, and complication.
Adolescent ; Blood Glucose ; Body Mass Index ; Body Weight ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Fasting ; Follow-Up Studies ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Hypoglycemia ; Insulin ; Insulin Lispro ; Insulin, Long-Acting ; Plasma

OBJECTIVE: To determine whether administrating insulin four times daily, compared to 1-3 times daily, improves maternal and perinatal outcomes of diabetes. METHODS: From August 1998 to April 2004, the 14 pregnant diabetic women were treated with four times daily administration of NPH and insulin-lispro and 15 pregnant diabetic women were treated with 1-3 times daily administration of Mixtard (30% RI, 70% NPH) or NPH. We compared the maternal and fetal complications between two groups. The goals for therapy are to achieve and maintain normoglycemia (premeal whole blood capillary glucose levels of less than 90 mg/dL and 1-hour after-meal levels of less than 120 mg/dL). RESULTS: The pregnant diabetic women who were treated with four times daily administration of NPH and Insulin lispro, instead of 1-3 times daily administration of Mixtard or NPH, resulted in better maternal and fetal outcome. But there was no significant difference between two groups statistically. CONCLUSION: This study reveals that this four times daily administration of NPH and insulin-lispro protocol achieved the glucose target level without maternal hypoglycemic events and helped to reduce the perinatal complications in pregnant diabetic women.
Capillaries ; Female ; Glucose ; Humans ; Insulin Lispro ; Insulin* ; Pregnancy*

Adolescent ; Adult ; Aged ; Blood Glucose ; analysis ; Cross-Over Studies ; Diabetes Mellitus ; blood ; drug therapy ; Female ; Glycated Hemoglobin A ; analysis ; Humans ; Insulin ; analogs & derivatives ; therapeutic use ; Insulin Lispro ; Male ; Middle Aged