OBJECTIVE: To evaluate the safety, effectiveness and health-related quality of life (HRQoL) parameters of A1chieve study participants in the Philippine cohort, who were treated with BIAsp 30.
METHODOLOGY: A1chieve is a non-interventional, six-month, observational study of 66,726 people with type 2 diabetes mellitus (T2DM), including both insulin users and non-insulin users, started on insulin detemir, insulin aspart, or BIAsp 30 in 28 countries across four continents. The present study evaluates the safety, effectiveness and HRQoL in 1,252 subjects from the Philippine cohort of the A1chieve study who were treated with BIAsp 30.
RESULTS: At baseline, the mean age, duration of diabetes and mean BMI were found to be 55.5±11.7 years, 7.2 ± 5.6 years and 25.4 ± 5.3 kg/m2, respectively. Seventy-eight percent (78%) of subjects were insulin naïve and 22% were prior insulin users. At baseline, glycemic control was poor (HbA1c = 9.9%) in the entire cohort. Overall there was a 2.7% reduction in mean HbA1c and 44.2% subjects achieved the HbA1c target of <7.0%, after 24 weeks of therapy with BIAsp 30. There were significant reductions in total cholesterol, LDL-cholesterol, triglycerides and systolic blood pressure after 24 weeks of therapy with BIAsp 30. There was no increase in the incidence of hypoglycemia among insulin-naïve subjects, while there was a marked reduction in hypoglycemia (4.93 to 2.53 events/person-year) among prior insulin users at 24 weeks.
CONCLUSION: BIAsp 30 is safe and efficacious for initiating and intensifying insulin therapy for Filipino T2DM patients.

Human ; Male ; Female ; Middle Aged ; Adult ; Insulin Aspart ; Insulin ; Diabetes Mellitus, Type 2 ; Hemoglobin A, Glycosylated ; Cholesterol, Ldl ; Triglycerides ; Insulin, Isophane

Background: The high prevalence of type 2 diabetes mellitus (T2DM) in the Philippines has burdened the health care system. Therefore, we compared the standard of care Insulin 30/70 + Insulin Glulisine (Arm B) to a traditional insulin regimen NPH Insulin + Regular Insulin (Arm A) to test the concept that both insulin regimens provide comparable effectiveness and safety in real-world practice. Methods : This is a ‘proof-of-concept,’ prospective, randomized, open label pragmatic study of 40 consecutive Filipino T2DM patients from October 2015 to June 2016. The primary endpoint was a reduction in HbA1c at 12 weeks. The secondary endpoints were changes in Fasting Plasma Glucose (FPG), Post Prandial Glucose (PPG), Capillary Blood Sugar (CBS), weight and insulin dose at 12 weeks. ANCOVA and Fisher’s exact tests were used. Results : Patients in treatment arm A showed comparable glycemic control to arm B as measured by reductions in HbA1c (2.89% vs. 2.67%; P = 0.657), FPG (65.94 vs. 46.71 mg/dl; P = 0.57), PPG (76.49 vs. 86.96 mg/dl; P = 0.271) and CBS (115.15 vs. 145.95 mg/dl; P = 0.420). Both treatment arms reported similar weight gain (1.92 vs. 1.22 kg), experienced similar incidence of hypoglycemia (7 vs. 6 patients) and adverse events (AE) (8 vs. 8 patients). Conclusion The traditional combination of NPH Insulin + Regular Insulin offers comparable glycemic control and tolerance as the standard of care without any new safety signals in the Filipino T2DM population. With a lower price, it can be one of the strategies to reduce the fi nancial burden of antidiabetic treatment.
Insulin, Isophane ; Insulin ; Diabetes Mellitus, Type 2

Allergic reaction to insulin is mediated by several mechanisms; differences in amino acid sequence of animal and human insulin, altered tertiary structure of insulin and the presence of non-insulin protein contaminants or pharmaceutical additives. Anaphylactic reactions to insulin only occur in 0.1 to 2% of patients who stopped insulin therapy and have then resumed treatment. We report a diabetic patient who suffered severe anaphylactic reactions to human recombinant insulin, successfully treated by desensitization. A 19-year-old man with type 1 diabetes receiving Insulatard HM(R) developed generalized urticaria and angioedema with progression to dyspnea, dizziness and syncope. Skin prick test to all kinds of human recombinant insulin products revealed immediate type hypersensitivity and the titer of insulin IgE was increased in serum. The desensitization trial with Velosulin HM(R) using modified desensitization method was performed. Six months after the desensitization he was taking Velosulin HM(R) as well as Insulatard HM(R) without any evidence of systemic allergic reactions.
Amino Acid Sequence ; Anaphylaxis* ; Angioedema ; Animals ; Dizziness ; Dyspnea ; Humans* ; Hypersensitivity ; Immunoglobulin E ; Insulin* ; Insulin, Regular, Pork ; Skin ; Syncope ; Urticaria ; Young Adult ; Isophane Insulin, Human

PURPOSE: The purpose of this study was to investigate the changes of collagen and the effect of insulin therapy on the collagen of the corpus cavernosum in diabetes mellitus(DM). MATERIALS AND METHODS: Twenty seven rats were included for this study and divided into control, diabetic and insulin treated diabetic group. DM was induced by intravenous injection of streptozotocin 65mg/kg and NPH insulin (initially 4IU/d for 3 days and then 6IU/d) was administered for 4 weeks for insulin treatment. After 4 weeks of experiment, the collagen concentration was evaluated with hydroxyproline quantitative analysis and collagen distribution within the corpus cavernosum. Collagen(type I, III and IV) was obsened with Masson-trichrome and immunohistochemical staining. RESULTS: 1. Body weights of control, diabetic group and insulin treated diabetic group were 315.0 +/-14.2gm, 230.8+/-15.2gm and 310.1+/-15.4gm, respectively, at 4 weeks of experiment. Control and insulin treated diabetic group progressively increased in body weight(p<0.05), while diabetic group decreased in body weight. 2 Collagen concentration of control, diabetic and insulin treated diabetic group expressed 465.2+/-24microgram, 590.3+/-43.7microgramand 567.1+/-34.8microgram respectively. Collagen concentration in corpus cavemosum significantly increased in diabetic and insulin treated diabetic group compared with control group(p<0.05). No significant difference was noted between diabetic and insulin treated diabetic group. 3. Immunohistochemical staining revealed collagen types I and III were distributed evenly in the corporal interstitial tissue, but type IV collagen was noted along the basement membrane of the cavernosal sinusoid in the both control and experimental groups. Collagen type 1 of diabetic and insulin treated diabetic group, as compared with control group, was noted thin staining in the corporeal tissue. There were no significant differences in collagen type 111 among control, diabetic and insulin treated diabetic groups. Collagen type IV of diabetic and insulin treated diabetic group, as compared with control group, was noted dense staining in the basement membrane of the cavernosal sinusoidal space. And the intensity for collagen type IV was not significantly different between diabetic and insulin treated diabetic group. 4. Masson-trichrome staining showed no significant differences among control, diabetic and insulin treated diabetic groups. CONCLUSIONS: These results suggest that the DM changes quantitatively the collagen type IV of corpus cavernosum and the insulin treatment had no effect on the collagen alteration in DM.
Animals ; Basement Membrane ; Body Weight ; Collagen Type IV ; Collagen* ; Diabetes Mellitus ; Hydroxyproline ; Injections, Intravenous ; Insulin* ; Insulin, Isophane ; Rats* ; Streptozocin

Biphasic Insulins ; Diabetes Mellitus, Type 2 ; drug therapy ; Female ; Humans ; Hypoglycemic Agents ; administration & dosage ; Insulin ; administration & dosage ; analogs & derivatives ; Insulin Aspart ; Insulin, Isophane ; Male ; Middle Aged ; Treatment Outcome

Although diabetic ketoacidosis is relatively common in primary diabetes mellitus, it is very rare in diabetes mellitus secondary to steroid therapy. We here present a case of diabetic ketoacidosis after steroid administration for minimal change nephrotic syndrome. A 29-year-old man was first admitted with generalized edema and massive proteinuria. He had no past history of diabetes mellitus. Kidney biopsy revealed minimal change disease and he was treated with prednisolone(1mg/kg). Eight weeks after steroid treatment, proteinuria disappeared completely and steroid dose was decreased by 10mg in a week. Nine weeks after steroid treatment, diabetes mellitus newly develped and it was well controlled with insulin therapy. As prednisolone dose was decreased, insulin requirement also diminished. When he was taking 30mg of prednisolone, insulin therapy was stopped because of good glycemic control. He complained of vomitting and abdominal pain, and tachypnea a week after withdrawl of insulin. Laboratory findings revealed severe diabetic ketoacidosis. Steroid was stopped and he was treated with fluid, insulin and potassium. Now he is beibg successfully treated with 20 unit of NPH insulin without relapse of nephrotic syndrome.
Abdominal Pain ; Adult ; Biopsy ; Diabetes Mellitus ; Diabetic Ketoacidosis* ; Edema ; Humans ; Insulin ; Insulin, Isophane ; Kidney ; Nephrosis, Lipoid* ; Nephrotic Syndrome ; Potassium ; Prednisolone ; Proteinuria ; Recurrence ; Tachypnea

BACKGROUND: The purpose of this study was to evaluate change in glycosylated hemoglobin (HbA1c), side effects, and quality of life (QOL) after a 16-week treatment period with Biphasic insulin aspart 30/70 (BIasp30) in patients with type 2 diabetes mellitus (T2DM) who had been suboptimally controlled with oral antidiabetic drugs (OADs). METHODS: The study consisted of a 4-week titration period when concurrent OAD(s) were replaced with BIasp30 and followed by a 12-week maintenance period. All patients completed the Diabetes Treatment Satisfaction Questionnaire at the beginning and the end of the trial. Hypoglycemic episodes were recorded by the patient throughout the trial. RESULTS: Sixty patients were included, of whom 55 patients (92%) completed the full 16-week treatment period. Seven-point blood glucose was significantly improved as compared with the baseline, except for the postlunch blood glucose level. HbA1c at the end of period was significantly improved from 9.2% to 8.2% (P<0.001). Eleven percent (n=6) of patients achieved HbA1c values < or =6.5% and 22% (n=12) of patients achieved <7.0%. There were 3.4 episodes/patients-year of minor hypoglycemia and 0.05 episodes/patients-year of major hypoglycemia. QOL showed significant changes only in the acceptability of high blood glucose category (P=0.003). CONCLUSION: Treatment with once or twice daily BIasp30 may be an option for the patients with T2DM suboptimally controlled with OADs in Korea. However, considering the low number of patients achieving the HbA1c target and the high postlunch blood glucose levels, additional management with another modality may be required for optimal control.
Biphasic Insulins ; Blood Glucose ; Diabetes Mellitus, Type 2 ; Hemoglobin A, Glycosylated ; Humans ; Hypoglycemia ; Hypoglycemic Agents ; Insulin Aspart ; Insulin, Isophane ; Korea ; Quality of Life

BACKGROUND: A1chieve(R) was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. METHODS: Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints. RESULTS: Out of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7+/-15.9 to 72.5+/-13.5) while the mean body weight was slightly increased (0.6+/-3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%+/-2.2%, 2.5+/-4.7 mmol/L, and 4.0+/-6.4 mmol/L, respectively. CONCLUSION: The studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.
Biphasic Insulins ; Body Weight ; Diabetes Mellitus, Type 2 ; Drug Toxicity ; Fasting ; Glucose ; Hemoglobins ; Humans ; Incidence ; Insulin ; Insulin Aspart ; Insulin, Isophane ; Insulin, Long-Acting ; Patient Selection ; Plasma ; Quality of Life ; Republic of Korea ; Treatment Outcome ; Insulin Detemir

BACKGROUNDThe clinical importance of glycaemic control in patients with diabetes has been well established. This study aimed to explore twice-daily biphasic insulin aspart 30 (BIAsp 30) for insulin initiation in patients with type 2 diabetes mellitus (T2DM) who had poor glycaemic control with human insulins (HIs). We use data from a Chinese cohort of the PRESENT study.

METHODSIn the 3-month study, Chinese subjects with T2DM started insulin therapy with BIAsp 30 in routine care. Glycaemic control was measured by glycosylated hemoglobin (HbA(1C)), fasting plasma glucose (FPG) and posting plasma glucose (PPG). The safety assessment included hypoglycaemia and other adverse events.

RESULTSA total of 1989 subjects previously treated with His were switched to BIAsp 30 for 3-month treatment. Mean HbA(1C), FPG and PPG were significantly improved after the therapy. The overall rate of hypoglycaemia decreased at the end of the trial except for the patients previously treated with long-acting insulin. Most of the events were minor and diurnal hypoglycaemia. Only one serious adverse drug reaction (SADR), a local hypersensitivity, was reported. The majority of the patients (> or = 96.7%) and physicians (> or = 84.7%) were either satisfied or very satisfied with the treatment using BIAsp 30 compared with previous HI therapy.

CONCLUSIONThe BIAsp 30 treatment improved both glycaemic control and patients' satisfaction without increasing hypoglycaemia in T2DM subjects inadequately controlled by His.

Adult ; Biphasic Insulins ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; Female ; Glycated Hemoglobin A ; drug effects ; Humans ; Insulin ; administration & dosage ; adverse effects ; analogs & derivatives ; pharmacology ; therapeutic use ; Insulin Aspart ; Insulin, Isophane ; Male ; Middle Aged ; Prospective Studies ; Treatment Outcome

The purpose of this study was to determine the effects oftaurine supplementation and taurine depletion on blood glucose and blood lipid concentrations in insulin-treated diabetic rats. Four groups of Sprague-Dawley male rats were fed the purified diet for 3 weeks ; nontaurine-supplemented diabetic rats(E0), nontaurine-supplemented diabetic rats with insulin treatment(E0+I), 1% taurine-supplemented diabetic rats with insulin treatment(E1+I) and taurine-depleted diabetic rats with insulin treatment(EA+I). Diabetes was induced by streptozotocin injection(50mg/kg B.W.). Isophane insulin was given subcutaneously into the abdominal wall of the diabetic rats(4 unit/rat/day). E1+I were supplemented with 1% taurine in drinking water. To induce taurine depletion, EA+I were treated with 5% beta-alanine in drinking water. E1+I had significantly higher body weight compared to that fo E0. The food intakes of E1+I and E0+I were significantly decreased compared to that of E0. There was no sigfniciant difference in food intake between E1+I and E0+I. The water intake of rats was significantly different among the groups ; E0>E0+I>E1+I>EA+I. The urine volume of E0 was significantly increased compared to those of insulin-treated goups. The blood glucose concentration of E0 was significantly increased compared to those of insulin-treated groups. In the oral glucose tolerance test(OGTT), E0+I and E1+I had significantly lower blood blucose concentrations compared to E0 after 30 min. Also EA+I had significantly lower bloodglucose concentrtion compared to E0 and E0+I. The plasma total cholesterol and LDL-cholesterol concentratons of EA+I were significantly incrased compared to those of other groups. Therefore, it may be suggested that tuarine supplementation is useful for insulin-dependent diabetes in order to prevent diabetic complications suchas cardiac vascular diseases.
Abdominal Wall ; Animals ; beta-Alanine ; Blood Glucose* ; Body Weight ; Cholesterol ; Diabetes Complications ; Diet ; Drinking ; Drinking Water ; Eating ; Glucose Tolerance Test ; Humans ; Insulin ; Insulin, Isophane ; Male ; Plasma ; Rats* ; Rats, Sprague-Dawley ; Streptozocin ; Taurine* ; Vascular Diseases