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Insulin analogues can reduce gestational hyperglycemia more safely and effectively because their molecular structure and metabolic characteristics are more consistent with the characteristics of gestational glucose metabolism. However, the safety and effectiveness of some insulin analogues in pregnancy remain unclear. At present, only a few insulin analogues, insulin aspart, insulin lispro and insulin detemir, have been approved for use during pregnancy in China. As for misuse or off-label insulin analogues during pregnancy, clinicians should make adjustments based on published clinical safety data. In this review, the safety and progress in the management of gestational hyperglycemia with rapid- and long-acting insulin analogues and insulin degludec/insulin aspart are reviewed to provide reference for insulin therapy during pregnancy.
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Compared with human insulin, insulin lispro shows a faster hypoglycemic effect and a higher peak plasma concentration, which can better control postprandial hyperglycemia. In this study, we used a solid phase extraction pretreatment method and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify insulin lispro in rat plasma. Bovine insulin was used as an internal standard. Plasma samples were separated on an ACQUITY UPLC Peptide CSH C18 column (2.1 mm × 50 mm, 1.7 μm) after solid phase extraction. Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 1 162.5→217.2 for insulin lispro and m/z 1 157.5→136.0 for insulin bovine (internal standard). The method validation results showed that the linear range was 0.1 ng·mL-1 - 100 ng·mL-1; intra- and inter-day accuracy and precision met the acceptance criteria for biological sample analysis. The recovery of insulin lispro ranged from 63.1% to 68.1%. The method was applied in a pharmacokinetic study of insulin lispro following a single-dose subcutaneous administration to rats. Animal experiments were approved by the Experimental Animal Ethics Committee of Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
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Objective:To evaluate the short-term economic effects of four kinds of premixed insulin in newly diagnosed type 2 dia-betes mellitus. Methods:A total of 120 newly diagnosed patients with type 2 diabetes mellitus were divided into four groups according to the kind of premixed insulin, group A was treated with insulin aspart 30 injection, group B was treated with insulin lispro 25 injec-tion, group C was treated with isophane protamine biosynthetic human insulin injection and group D was treated with protamine zinc re-combinant human insulin injection. The course of treatment was three months. The therapy efficacy was assessed by the remission rate in three months. The short-term economic effect was evaluated by the cost-minimization analysis method. Results:The remission rate of group A, B, C and D respectively was 48. 39%, 48. 28%, 51. 61% and 51. 72% without significant difference (P>0. 05). The average cost per person of the four groups was 1195. 52, 1202. 41, 1220. 69 and 1258. 84 yuan, and the average medicine cost per person was 750. 52, 689. 41, 754. 69 and 764. 34 yuan, respectively. There was no significant difference in cost among the four groups (P >0. 05). Conclusion:All the four kinds of premixed insulin can be used for the starting treatment with the similar total cost, and in relative terms, aspart 30 injection and insulin lispro 25 injection are better for the initial treatment of diabetes.
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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.
Subject(s)
Humans , Diabetes Mellitus, Type 2 , Fasting , Glucagon-Like Peptide-1 Receptor , Glucose , Hypoglycemia , Insulin Glargine , Insulin Lispro , Insulin , Korea , Meals , Metformin , Obesity , Prevalence , Weight GainABSTRACT
Objective To compare the efficacy and safety of recombinant insulin lispro and insulin lispro in the treatment of type 2 diabetes mellitus(T2DM ) .Methods Forty‐eight T2DM patients with poor blood glucose control were randomly assigned to the recombinant insulin lispro group (observation group ,n=32) and insulin lispro group (control group ,n=16) according to the ratio of 2∶1 .On the basis of injection of the recombinant insulin glargine once daily before sleep ,the two groups were given the re‐combinant insulin lispro injection or insulin lispro injection once before each meal .The period of treatment was 16 weeks .The levels of HbA1c ,2 h postprandial blood glucose(2hPG) and fasting plasma glucose(FPG) before and after treatment were measured and compared between the two groups .The adverse events were evaluated at the end of treatment .Results Forty‐four cases finished the study ,28 cases in the observation group and 16 cases in the control group .The levels of HbA1c ,FPG and 2hPG after 16‐week treatment in the two groups were decreased significantly (P0 .05) .Conclusion The recombinant insulin lispro injection has non‐inferiority effects in the aspect of effectiveness compared with the lispro insulin injection ,moreover they have the same safety .
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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.
Subject(s)
Adult , Humans , Blood Glucose , Brain Injuries , Electroencephalography , Glasgow Coma Scale , Glucagon , Glucose , Hypoglycemia , Infusions, Intravenous , Insulin Lispro , Insulin , Intensive Care Units , Intubation, Intratracheal , Lorazepam , Magnetic Resonance Imaging , Phenytoin , Plasma , Pneumonia, Ventilator-Associated , SeizuresABSTRACT
Objective To investigate the mixed protamine zinc recombinant human insulin lispro injection on glucose metabolism, immune function in patients with type 2 diabetes and its inflammatory mechanisms.Methods 125 patients enrolled were randomly divided into two groups according to the random number table: control group (n =61) and observation group (n =64).The control group were received conventional treatment, observation group were received mixed protamine zinc recombinant human insulin lispro injection on the basis of control group, with a course of three months of both groups.The fasting blood glucose (FBG), 2h post prandial blood glucose (2hPG), glycated hemoglobin (HbA1c), fasting insulin, insulin resistance index ( IRI) , CD4 +, CD8 +, CD4 +/CD8 +changes and inflammatory cytokines levels were compared before and after treatment between two groups. Results The level of FBG, 2hPG, HbA1c after treatment was respectively lower than that before treatment in both groups (P<0.05), and the above indexes of observation group after treatment was respectively lower than that of control group (P<0.05).The level of fasting insulin, IRI after treatment was respectively lower than that before treatment in both groups (P<0.05), and the above indexes of observation group after treatment was respectively lower than that of control group (P<0.05).The level of CD8 +was lower, CD4 +, CD4 +/CD8 +was higher after treatment than that before treatment in both groups, respectively (P<0.05), and the CD8 +level of observation group after treatment was lower, CD4 +, CD4 +/CD8 +was higher than that of control group, respectively (P<0.05).The level of TNF-α, IL-6, CRP after treatment was respectively lower than that before treatment in both groups (P<0.05), and the above indexes of observation group after treatment was respectively lower than that of control group (P<0.05).Conclusion The mixed protamine zinc recombinant human insulin lispro injection can significantly improve glucose metabolism in patients with type 2 diabetes, and enhance immune function, reduce inflammation, thereby reducing the incidence of cardiovascular events.
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The incidence and prevalence of type 1 diabetes in children and adolescents are increasing around the world,along with the suboptimal glucose control and higher incidence of long-term chronic complications during adulthood.Achieving good glycemic control and avoiding brain function damages induced by hypoglycemia are important when treating type 1 diabetes.Insulin lispro,a rapid-acting insulin used either alone or in combination with basal insulin analogue,can be effective,safety,and flexible.
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Objective To evaluate the therapeutic effect and safety of insulin lispro mix 50/50 combined with mefformin in newly diagnosed overweight/obese type 2 diabetic mellitus patients.Methods Sixty-two patients with newly diagnosed overweight/obsess type 2 diabetic mellitus were randomly divided into observation group (32 cases) and control group (30 cases) by systematic sampling method.The observation group received insulin lispro mix 50/50 combined with metformin,and the control group received recombinant human insulin and insulin glargine.The therapeutic effect and safety were compared between the 2 groups.Results There were no statistical differences in the blood glucose before eating,before retiring and at mane primo 3:00 between the 2 groups (P ＞ 0.05).There were no statistical differences in the time of blood glucose standard and rate of hypoglycaemia between the 2 groups (P ＞ 0.05).Daily insulin dosage and costs in the observation group were lower than those in the control group [(0.6 ± 0.1) U/kg vs.(0.8 ± 0.1) U/kg and (15.8 ±2.1) yuan/d vs.(21.3 ±2.6) yuan/d],and there were statistical differences (P ＜0.05).Conclusion Insulin lispro mix 50/50 combined with mefformin provides a convenient,effective and safe therapy for newly diagnosed overweight/obese type 2 diabetic mellitus patients and high cost performance.
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Pregnancy affects both maternal and fetal metabolism, and even in non-diabetic women, it exerts a diabetogenic effect. Among pregnant women, 2% to 14% develop gestational diabetes. Pregnancy can also occur in women with preexisting diabetes, which may predispose the fetus to many alterations in organogenesis, restrict growth, and the mother, to some diabetes-related complications, such as retinopathy and nephropathy, or to acceleration of the course of these complications, if they are already present. Women with gestational diabetes generally start their treatment with diet and lifestyle changes; when these changes are not enough for optimal glycemic control, insulin therapy must then be considered. Women with type 2 diabetes using oral hypoglycemic agents are advised to change to insulin therapy. Those with preexisting type 1 diabetes should start intensive glycemic control. As basal insulin analogues have frequently been used off-label in pregnant women, there is a need to evaluate their safety and efficacy. The aim of this review is to report the use of both short- and long-acting insulin analogues during pregnancy and to enable clinicians, obstetricians, and endocrinologists to choose the best insulin treatment for their patients.
A gravidez afeta tanto o metabolismo materno quanto o fetal e, mesmo em mulheres não diabéticas, apresenta um efeito diabetogênico. Entre as mulheres grávidas, 2% a 14% desenvolvem o diabetes gestacional. A gravidez pode ocorrer também em mulheres já diabéticas, o que pode predispor o feto a muitas alterações na organogênese, restrição de crescimento e a mãe a algumas complicações relacionadas ao diabetes, tais como retinopatia e nefropatia, ou acelerar o curso dessas complicações se já estiverem presentes. Pacientes com diabetes gestacional geralmente iniciam seu tratamento com dieta e mudanças no estilo de vida; porém, quando essas medidas falham em atingir um controle glicêmico adequado, a insulinoterapia deve ser considerada. Pacientes com diabetes tipo 2 em uso de hipoglicemiantes orais são aconselhadas a iniciar o uso de insulina. Pacientes com diabetes tipo 1 preexistente devem iniciar um controle glicêmico estrito. Em função do fato de os análogos basais de insulina estarem sendo utilizados muito frequentemente off-label em pacientes grávidas, faz-se necessário avaliar sua segurança e eficácia nessa condição. O objetivo desta revisão é avaliar o uso de tais análogos, tanto de ação curta como prolongada, durante a gravidez, para possibilitar médicos clínicos, obstetras e endocrinologistas escolher o melhor regime terapêutico para suas pacientes.
Subject(s)
Female , Humans , Pregnancy , Diabetes Mellitus, Type 1/drug therapy , /drug therapy , Hypoglycemic Agents/therapeutic use , Insulin, Long-Acting/therapeutic use , Insulin, Short-Acting/therapeutic use , Pregnancy in Diabetics/drug therapy , Blood Glucose/metabolismABSTRACT
Insulin therapy is indicated in the treatment of gestational diabetic women and overt diabetic pregnant women for hyperglycemia after failure to respond to the diets and exercise regimens. The insulin is administered to mimic normal pancreatic function. The normal pancreas secretes 50% of the total daily insulin as mealtime boluses. This delivery may be mimicked by four-injection-per-day of combination of NPH and regular insulin (RI). Hypoglycemia is a well-recognized complication of intensive insulin therapy in patients with Type II diabetes. Recently, it has been reported that insulin-lispro, an analogue of regular human insulin with a peak insulin action achieved with a 1 hour after injection improves postprandial glucose concentration in non-pregnant diabetic patients. Treatment of gestational or diabetic pregnant women with NPH and insulin-lispro has significantly lower postprandial glucose levels without an increase in hypoglycemic events. Here, we report 2 cases of hyperglycemic control with four times daily administration of NPH & insulin-lispro on diabetes in pregnancy, with brief reviews.
Subject(s)
Female , Humans , Pregnancy , Diabetes Mellitus , Diet , Glucose , Hyperglycemia , Hypoglycemia , Insulin Lispro , Insulin , Meals , Pancreas , Pregnant WomenABSTRACT
Objective To assess the efficacy and safety of insulin Lispro in type 1 or type 2 diabetic patients.Methods Forty diabetic patients were assigned to receive premeal insulin Lispro plus bedtime Neutral Protamine Hagedorn(NPH)insulin for 12 weeks.The following characters were compared between before and after treatment,including fasting plasma glucose(FPG),1 h and 2 h postprandial glucose(after a standardized meal),glycosylated hemoglobin(GHbA_1c)levels,total daily insulin dose and the number of hypoglycemic episodes.Results Thirty-nine subjects fulfilled the study.After 12 weeks of Lispro treatment,the levels of FPG and 1 h and 2 h postprandial glucose were decreased significantly,being 1.12 mmol/L,2.37 mmol/L and 1.92 mmol/L respectively;GHbA_1c was decreased by 1.45%(from 8.9% to 7.5%).The dose of insulin Lispro was not changed,compared with the dose of regular human insulin at baseline.The incidence of hypoglycemia was decreased from 19.5 every week at baseline to 9.8 every week with Lispro.Conclusion Insulin Lispro is an effective agent for good glucose control with fewer hypoglycemic episodes in diabetic patients.
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The effects of human insulin 70/30 and insulin lispro 75/25 were compared in improving postprandial blood glucose excursions in 106 patients with type 1 or 2 diabetes in a one-month,open-labelled,self- controlled trial .The results showed that treatment of diabetic patients with insulin lispro 75/25 significantly improved 2 h postprandial blood glucose excursion compared to pre-study with human insulin 70/30 (baseline) without any significant adverse events or sustained hypoglycemic episodes.These physiological benefits were associated with a patient preference for insulin lispro 75/25.