Intermediate-acting Human Insulin Research Articles

A medication-wide association study to identify medications associated with incident clinically significant diabetic retinopathy.

Diabetic retinopathy, a common microvascular complication of diabetes mellitus, is one of the leading causes of vision loss worldwide. Although some oral drugs have been suggested to affect the risk of diabetic retinopathy, systematic evaluation about the associations between medications and diabetic retinopathy is still absent. To comprehensively investigate associations of systemic medications with incident clinically significant diabetic retinopathy (CSDR). Population-based cohort study. From 2006 to 2009, more than 26 000 participants residing in New South Wales were enrolled in the 45 and Up study. Diabetic participants with self-reported physician diagnosis or records of anti-diabetic medication prescriptions were finally included in the current analysis. CSDR was defined as diabetic retinopathy cases requiring retinal photocoagulation recorded in the Medicare Benefits Schedule database from 2006 to 2016. Prescriptions of systemic medication from 5 years to 30 days prior to CSDR were retrieved from the Pharmaceutical Benefits Scheme. The study participants were equally split into training and testing datasets. Logistic regression analyses were performed for the association between each of systemic medication and CSDR in the training dataset. After controlling the false discovery rate (FDR), significant associations were further validated in the testing dataset. The 10-year incidence of CSDR was 3.9% (n = 404). A total of 26 systemic medications were found to be positively associated with CSDR, among which 15 were validated by the testing dataset. Additional adjustments for pertinent comorbidities suggested that isosorbide mononitrate (ISMN) (OR: 1.87, 95%CI: 1.00-3.48), calcitriol (OR: 4.08, 95% CI: 2.02-8.24), three insulins and analogues (e.g., intermediate-acting human insulin, OR: 4.28, 95% CI: 1.69-10.8), five anti-hypertensive medications (e.g., furosemide, OR: 2.53, 95% CI: 1.77-3.61), fenofibrate (OR: 1.96, 95% CI: 1.36-2.82) and clopidogrel (OR: 1.72, 95% CI: 1.15-2.58) were independently associated with CSDR. This study investigated the association of a full spectrum of systemic medications with incident CSDR. ISMN, calcitriol, clopidogrel, a few subtypes of insulin, anti-hypertensive and cholesterol-lowering medications were found to be associated with incident CSDR.

A nationwide cohort study for comparative vascular safety of long-acting insulin analogue versus intermediate-acting human insulin in type 2 diabetes

Little is known about the comparative vascular safety of basal insulins (intermediate-acting human insulin [IAHI] or long-acting insulin analogue [LAIA]) in type 2 diabetes (T2D). This study sought to examine the vascular and hypoglycemic effects associated with IAHI versus LAIA in real-world patients with T2D. We utilized Taiwan’s National Health Insurance Research Database to identify T2D patients who stably used IAHI (N = 11,521) or LAIA (N = 37,651) in the period 2004–2012. A rigorous three-step matching algorithm that considered the initiation date of basal insulin, previous exposure of antidiabetic treatments, comorbidities, diabetes severity and complications, and concomitant medications was applied to achieve the between-group comparability. Study outcomes, including cardiovascular diseases (CVDs), microvascular diseases (MVDs), and hypoglycemia, were assessed up to the end of 2013. Compared with LAIA, the use of IAHI was associated with greater risks of composite CVDs (adjusted hazard ratio [aHR]: 1.79; 95% confidence interval [CI] 1.20–2.67) and hospitalized hypoglycemia (aHR: 1.82; 95% CI 1.51–2.20), but a lower risk of composite MVDs (aHR: 0.88; 95% CI 0.84–0.91). Subgroup and sensitivity analyses showed a consistent trend of results with that in the primary analyses. In summary, although the use of IAHI versus LAIA among T2D patients in usual practice may be associated with a lower risk of MVDs, strategies should be optimized for minimizing the risks of hypoglycemia and CVDs in this population.

The Use of Long-Acting Insulin Analogs and the Risk of Colorectal Cancer Among Patients with Type 2 Diabetes: A Population-Based Cohort Study.

The association between long-acting insulin analogs and colorectal cancer is uncertain, with previous studies reporting discrepant findings. To determine whether the use of long-acting insulin analogs is associated with an increased risk of colorectal cancer, when compared with use of intermediate-acting human insulins among patients with type 2 diabetes. We conducted a population-based study using the United Kingdom Clinical Practice Research Datalink (CPRD). We identified patients newly treated with either a long-acting insulin analog or an intermediate-acting human insulin between September 1, 2002 and January 31, 2018, with follow-up until January 31, 2019. Each long-acting insulin analog user was propensity score-matched to one intermediate-acting human insulin user, and a lag of 1year was imposed. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of colorectal cancer, comparing long-acting insulin analogs with intermediate-acting human insulin. Secondary analysis was conducted to assess whether there was a duration-response relationship. A total of 10,734 new long-acting insulin analog users were matched to 10,734 new intermediate-acting human insulin users. After a median follow-up of 2.8years, the use of long-acting insulin analogs was not associated with an increased risk of colorectal cancer, compared with intermediate-acting human insulin (1.80 vs. 1.87 per 1000 person-years, respectively; HR 0.96, 95% CI 0.70-1.34). There was no evidence of a duration-response relationship. The results of this population-based study indicate that use of long-acting insulin analogs is not associated with an overall increased risk of colorectal cancer.

Comparing lente insulin and NPH insulin for treating diabetic dogs

Diabetes mellitus is the second most common endocrinopathy in dogs. Once diagnosed, almost all dogs will require daily insulin administration for life. The most commonly used insulin types are neutral...

Glycaemic control using different regimens of intermediate- and short-acting insulin in childhood type 1 diabetes mellitus: an experience from a tertiary care centre

Multiple-dose insulin and insulin pump therapy have been found to have better glycaemic control in type 1 diabetes compared to other regimens. In developing countries where this may not be an option for all patients, the efficacy of regimens employing intermediate- and short-acting regimens needs to be determined. The objective of the present study is to compare the HbA1c-lowering efficacy of various regimens of short-acting and intermediate-acting human recombinant insulin in children with type 1 diabetes mellitus. Ninety-eight patients with type 1 diabetes were treated with various regimens of intermediate- and short-acting insulin, and their efficacy was compared. The mean HbA1c at enrolment was 11.34, 10.18 and 10.5 % among the different groups. Six months later, there was a significant reduction in HbA1c in patients on the thrice-daily variable mix of short- and intermediate-acting insulin (group A) compared to those on twice-daily premixed insulin (group B) or on the combination of once-daily premixed insulin and twice-daily short-acting insulin (p = 0.0003). There was a significant reduction in HbA1c in those who were shifted to the group A regimen after 6 months (p = 0023).

Long-acting Insulin Analogues and Diabetic Retinopathy: A Retrospective Cohort Study

PurposeLong-acting insulin analogues were developed to facilitate consistent glycemic control without excessive hypoglycemia. However, structural modifications of the insulin molecule can alter biological responses and binding characteristics with specific receptors. The aim of this study was to estimate the risk of sight-threatening diabetic retinopathy (STDR) associated with treatment using long-acting insulin analogues compared with intermediate-acting insulin in patients with type 2 diabetes mellitus (T2DM). MethodsA retrospective cohort consisting of patients with T2DM aged 20 years of age and older with newly initiated treatment with long-acting insulin analogues (glargine and detemir) and intermediate-acting human insulin was identified from the National Health Insurance database between January 2004 and December 2006 and was subdivided into different cohorts. The risk of the development of STDR was determined by Cox regression models and compared between different cohorts. FindingsOf the 46,739 eligible patients, initiators of insulin glargine, insulin detemir, and neutral protamine Hagedorn (NPH) insulin were identified for comparison using propensity-score matching methods. Long-acting insulin analogues were not associated with changed risk for STDR by intention-to-treat and time-varying use approaches between either matched or unmatched cohorts. ImplicationsThe strategies that aim at preventing diabetic retinopathy by treating T2DM patients with long-acting insulin analogues remain further prospective studies with longer follow-up period to validate our observations within an appropriate dosage range and to further evaluate the safety of long-acting insulin analogues on reducing the progression of diabetic retinopathy.

English

INTRODUCTION: Type 2 diabetes is a progressive disorder of β-cell dysfunction. Patients using oral therapy alone for it seldom achieve and maintain the recommended 7% HbA1c goal for glycemic control. However, the majority of patients with a longer duration of diabetes remain poorly controlled with oral agents, and use of insulin, which could improve glycemic control, is often long delayed and not aggressive enough. Glargine, a long-acting insulin analog with a more favourable 24-h time-action profile (no pronounced peak) than long- or intermediate-acting human insulin preparations, may be especially suited in this condition. AIMS: To compare the safety and efficacy of the long-acting analog insulin glargine and human premix insulin in patients with type 2 diabetes who were previously treated with oral hypoglycemic drugs alone but inadequately controlled. SETTINGS AND DESIGN: A total of 750 subjects with type 2 diabetes who were receiving oral hypoglycemic drugs for diabetes control were randomized to receive insulin glargine once daily (n = 370) or human premix insulin twice daily (n = 380) for 24 weeks in an open-label, tertiary centre study. Doses were adjusted systematically to obtain target fasting glucose < 100mg/dl. Outcomes included fasting blood sugar, HbA1c levels, change in weight and insulin dose from study start to end. STATISTICAL ANALYSIS: Qualitative variables were tested using Chi square test and p values were calculated between two groups. RESULTS: At the start of study, age range was 30-70 years, BMI was 26.48 +/- 6.3 kg/m (2) , and HbA1c was 11.9 +/-3.1%(mean +/- SD) for both group. The mean change (means ± SD) in HbA1c from baseline to end point was similar in the insulin glargine group (−3.0 ± 1.68%) and the human premix insulin group (−2.89 ± 1.79%) (P value =0.3861). The symptomatic hypoglycemic episodes were greater with human premix insulin than with glargine (significance level 0.00002).Subjects in the insulin glargine group experienced less weight gain than those in the premix human insulin group (0.4 vs. 1.4 kg, P < 0.0001). CONCLUSIONS: In patients with type 2 diabetes, once-daily bedtime insulin glargine is as effective as twice-daily human premix insulin in improving and maintaining glycemia control. In addition, insulin glargine demonstrates a lower risk of symptomatic hypoglycemia and less weight gain compared with human premix insulin. The treatments were associated with similar reductions in fasting glucose levels and HbA1c levels.

Insulin treatment of type 2 diabetes: Considerations when converting from human insulin to insulin analogs

Type 2 diabetes mellitus is a highly prevalent disease characterized by insulin resistance, hyperglycemia, and diminished pancreatic β-cell function. Conventional insulin products used to manage this disease include regular human insulin and intermediate-acting human insulin. However, due to several limitations imposed by human insulins, such as onset and duration of action that do not coincide with physiologic needs and increased risk of hypoglycemia, insulin analogs were developed. Because they more closely mimic the physiologic action of endogenous insulin, insulin analogs are associated with more effective glucose control, a lower risk of hypoglycemia, greater convenience, and, in some instances, less weight gain. Switching from human insulin to insulin analogs is easily accomplished. Several studies have demonstrated a high rate of success with patient-initiated, self-adjusted dosing algorithms compared to investigator/clinician-initiated dose adjustments. These studies and several other published guidelines on insulin analogs provide patients and clinicians with information pertaining to better treatment options and can help increase overall patient satisfaction.

Direct healthcare costs of patients with type 2 diabetes using long-acting insulin analogues or NPH insulin in a basal insulin-only regimen

Aims To compare direct healthcare costs incurred by patients with type 2 diabetes in Denmark prescribed long-acting insulin analogues (LAIA) or intermediate-acting human insulin (NPH) in a basal-only regimen. Methods Demographic and socio-economic patient characteristics, hospital utilisation data, primary care visits, specialist physician visits and prescription data were extracted from registers covering the Danish population. Patients receiving basal insulin were identified during a 1-year inclusion period (2005) and allocated to a LAIA ( n = 303) or NPH group ( n = 8523). LAIA patients were then matched with NPH patients using propensity scores based on observable covariates. Annual direct healthcare costs were determined during a <2-year analysis period (2005–2006). Results Direct healthcare costs, including prescription costs, were equivalent between groups. However, while most cost items were similar between groups, ambulatory visit costs were significantly lower in LAIA-treated patients ( p = 0.03), whereas insulin pharmacy costs were significantly lower in NPH-treated patients ( p < 0.001). Conclusion There was no difference in direct healthcare costs between patients using LAIAs or NPH insulin.

Use of insulin glargine during pregnancy: a case–control pilot study

To determine whether the use of insulin glargine during pregnancy is associated with an increase in the incidence of fetal macrosomia or adverse neonatal outcome. A matched case-control study. Women's Centre, John Radcliffe Hospital, Oxford, UK. Sixty-four pregnant women treated with insulin during their pregnancies, 20 with type I diabetes and 44 with gestational diabetes. Two groups of women were compared in matched pairs. A study group of 32 pregnant women with diabetes treated with insulin glargine during their pregnancy and a control group of 32 pregnant women treated with an intermediate-acting human insulin (isophane or insulin zinc suspension) and matched for weight at booking, height, gestation at delivery, parity, fetal sex, duration of insulin use in pregnancy and glycaemic control during the third trimester of pregnancy (glycosylated haemoglobin [HbA(1c)] concentration and mean blood glucose concentration). Birthweight, centile birthweight, the incidence of fetal macrosomia (birthweight > 90th percentile) and neonatal morbidity in the two study groups. There was no significant difference between the birthweight or centile birthweight of babies born to the women treated with insulin glargine during pregnancy and that of the babies born to those in the control group treated with intermediate-acting human insulin. The overall incidence of fetal macrosomia was 12/32 (37.5%) in the insulin glargine group and 13/32 (40.6%) in the control group. There was no significant difference in neonatal morbidity between the groups. The results of this pilot study indicate that insulin glargine treatment during pregnancy does not appear to be associated with increased fetal macrosomia or neonatal morbidity.

Combined effect of exercise and ambient temperature on insulin absorption and postprandial glycemia in type I patients.

We studied the combined effect of cool (10 degrees C) and warm (30 degrees C) ambient temperatures and physical exercise on insulin absorption and postprandial glycemia. Nine type I (insulin-dependent) diabetic patients were injected subcutaneously with their usual morning dose of short- and intermediate-acting human insulin and were given breakfast. Warm temperature was associated with 3- to 5-fold higher insulin absorption (P less than .01) and significantly lower blood glucose concentration (P less than .001) than cool temperature regardless of exercise. Exercise was associated with 28% (P less than .01) and 22% (P less than .05) increases in plasma insulin and maximally 5.7 mM (P less than .025) and 7.1 mM (P less than .01) lower blood glucose at cool and warm temperatures, respectively. Warm temperature and exercise had an additive effect in stimulating insulin absorption and in lowering blood glucose concentrations. However, there was no evidence of synergism between higher temperature and exercise in increasing free-insulin concentrations or decreasing blood glucose concentrations. To avoid postprandial hyperglycemia at cool temperature or hypoglycemia after exercise at warm temperature, appropriate adjustments in diet and insulin dose, or both, should be made.