Multiple Dose Insulin Injections Research Articles

Type 1 diabetes mellitus; ovarian reserve; anti-Müllerian hormone; ovarian function

BACKGROUND: Prolonged course of diabetes mellitus often leads to the development of vascular complications, insufficiency of ovarian function. The occurrence of diabetes mellitus in women before pregnancy (pregestational diabetes mellitus) it can have various adverse consequences for the mother, fetus, child and the course of pregnancy. Pregnancy planning in women with pregestational diabetes significantly improves the outcomes of pregnancy and childbirth. AIM: The aim of this study was to analyze gonadotropic and ovarian function parameters in patients with type 1 diabetes mellitus depending on the age of onset, duration and compensation level of the disease. MATERIALS AND METHODS: The patients included into this clinical prospective study were divided into two groups. The main group consisted of 216 patients with type 1 diabetes mellitus aged 18 to 39 years (mean age: 27.1 ± 3.1 years). The control group consisted of 30 healthy women of reproductive age. Chemiluminescent immunoassay was used to determine blood serum levels of anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, testosterone, free testosterone, and sex hormone-binding globulin from day 2 to day 5 of the menstrual cycle. Serum progesterone levels were measured on days 20–23 of the menstrual cycle for three consecutive cycles. Glycated hemoglobin levels were also studied in the blood serum of patients with type 1 diabetes mellitus. All the patients underwent pelvic ultrasound examination to assess the cohort of antral follicles and ovarian volume. RESULTS: The average age of menarche in patients with type 1 diabetes mellitus who developed the disease at the age of under 10 years was 14.2 ± 1.2 years. This was higher than in the group of girls with the onset of the disease over the age of 10 years (13.5 ± 1.2 years) and in women of the control group (11.9 ± 1.1 years). When assessing the ovarian reserve in patients with type 1 diabetes mellitus, we found a decrease in anti-Müllerian hormone level and antral follicle count in the group of women with disease onset at the age of under 10 years. We did not find differences in the ovarian reserve parameters in patients depending on disease duration. Normogonadotropic normoprolactinemic ovarian insufficiency was detected in 154 (71.3%) of 216 patients, while the rest 62 (28.7%) women had an ovulatory menstrual cycle. In patients with anovulation, luteal phase deficiency and ovulatory menstrual cycle, we found no differences between the age of development of type 1 diabetes mellitus, its duration, glycated hemoglobin levels, total daily insulin dose and insulin dose per kilogram of body mass. In patients receiving intensive insulin therapy with continuous subcutaneous insulin infusion, glycated hemoglobin level was lower than in those receiving multiple dose insulin injection therapy. CONCLUSIONS: The average age of menarche in patients with type 1 diabetes mellitus is higher than in healthy women. The ovarian reserve parameters in patients with early onset of the disease, before 10 years of age, are lower than in patients who developed type 1 diabetes mellitus after 10 years of age. Duration of pregnancy planning period depends on compensation level of the disease and lasts from six to 12 months. This requires the doctor and patient to prepare for the implementation of reproductive tasks as early as possible, especially in patients whose disease onset occurred in pre-pubertal period.

Connected Insulin Pens and Caps: An Expert's Recommendation from the Area of Diabetes of the Spanish Endocrinology and Nutrition Society (SEEN).

Undoubtedly, technological advances have revolutionised diabetes management in recent years. The development of advanced closed hybrid loop insulin pumps or continuous glucose monitoring (CGM) systems, among others, have increased the quality of life and improved glycaemic control of people with diabetes. However, only some patients have access to such technology, and only some want to use it. CGM has become much more widespread, but in terms of insulin delivery, most people with type 1 diabetes (T1D) and almost all people with type 2 diabetes (T2D) on insulin therapy are treated with multiple-dose insulin injections (MDI) rather than an insulin pump. For these patients, using connected insulin pens or caps has shown benefits in reducing missed insulin injections and promoting correct administration over time. In addition, using these devices improves the quality of life and user satisfaction. The integration of insulin injection and CGM data facilitates both users and the healthcare team to analyse glucose control and implement appropriate therapeutic changes, reducing therapeutic inertia. This expert's recommendation reviews the characteristics of the devices marketed or in the process of being marketed and their available scientific evidence. Finally, it suggests the profile of users and professionals who would benefit most, the barriers to its generalisation and the changes in the care model that implementing these devices can bring with it.

Clinical Characteristics, Molecular Features, and Long-Term Follow-Up of 15 Patients with Neonatal Diabetes: A Single-Centre Experience

Background: Diabetes diagnosed within the first 6 months of life is defined as neonatal diabetes mellitus (NDM). Mutations in the KCNJ11, ABCC8, and INS genes are the most common cause of permanent NDM. In populations with a high rate of consanguinity, Wolcott-Rallison syndrome caused by biallelic EIF2AK3 mutations is common. Methods: We studied the clinical characteristics and underlying genetic cause of disease in 15 individuals with diabetes onset before 6 months of age as defined by sustained hyperglycaemia requiring insulin treatment. Patients who had a remission of the diabetes, defined by a normal blood glucose and HbA1c value without insulin or sulphonylurea (SU) treatment, within the first 18 months of life were classified as having transient NDM (TNDM). Results: We report 15 patients with NDM from 14 unrelated families, including 10 with reported parental consanguinity. 1/15 patients had a remission of diabetes, leading to a diagnosis of TNDM. Mutations were detected in 80% (n = 12/15) of the cohort (ABCC8 [n = 4], PTF1A-distal enhancer [n = 3], KCNJ11 [n = 2], EIF2AK3 [n = 1], INS [n = 1], and SLC19A2 [n = 1]). All cases were initially treated with multiple dose insulin injections. One patient with an ABCC8 mutation transitioned from insulin to SU resulting in improved metabolic control at the age of 20 years. Conclusion: Although the number of individuals born to consanguineous parents was considerably high in this cohort, KATP channel mutations (ABCC8/KCNJ11) were more common than EIF2AK3 mutations (n = 6 vs. n = 1). Genetic analyses should be performed in all NDM cases due to the potential impact on treatment and prognosis.

Impact of sensor-augmented pump therapy with predictive low-glucose management on hypoglycemia and glycemic control in patients with type 1 diabetes mellitus: 1-year follow-up

AimsTo describe real-life experience with sensor-augmented pump therapy with predictive low-glucose management (SAPT-PLGM), in terms of hypoglycemia and glycemic control after one year of follow-up in T1D patients with hypoglycemia as the main indication of therapy. MethodsRetrospective cohort study under real life conditions. Baseline and one-year follow-up variables of glycemic control, hypoglycemia and glycemic variability were compared. ResultsFifty patients were included, 31 on prior treatment with SAPT with low-glucose suspend (LGS) feature and 19 on multiple dose insulin injections (MDI). Mean HbA1c decreased in the MDI group (8.24%–7.08%; p = 0.0001). HbA1c change was not significant in the SAPT-LGS group. Area under the curve (AUC) below 70 mg/dl improved in both SAPT-LGS and MDI groups while AUC, %time and events below 54 mg/dl decreased in SAPT-LGS group. Glycemic variability improved in the MDI group. Less patients presented severe hypoglycemia with SAPT-PLGM in both groups, however the change was non-significant. ConclusionsUnder real life conditions, SAPT-PLGM reduced metrics of hypoglycemia in patients previously treaded with MDI and SAPT-LGS without deteriorating glycemic control in SAPT-LGS patients, while improving it in patients treated with MDI.

Evaluation of FreeStyle Libre Flash Glucose Monitoring System on Glycemic Control, Health-Related Quality of Life, and Fear of Hypoglycemia in Patients with Type 1 Diabetes.

Background/objectives:In the current era of modern technology and the development of smart devices such as the flash glucose monitoring (FGM) systems, patients can easily monitor their glucose levels more frequently without any inconvenience. In this study, we evaluate the effect of FreeStyle Libre FGM system on glycemic control, hypoglycemia, health-related quality of life (QoL), and the fear of hypoglycemia (FOH) among children and young people with type 1 diabetes (T1D).Design and methods:A prospective study was conducted at the Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh, Saudi Arabia, between January 2017 and May 2017 on 47 (aged 13-19 years) registered patients with T1D who used conventional finger-pricking method for self-testing the glucose. At baseline visit, the FGM sensors were placed on each participant by a trained diabetes educator. The data collected from the sensors were computed to generate the respective ambulatory glucose profiles so as to determine the total number of scans conducted during the study period. At the baseline and at 3 months of the experiment, a trained interviewer administered the questionnaire Hypoglycemia Fear Survey-Child Version (HFS-C) and PedsQL 3.0 (QoL questionnaire) to each patient. The age, sex, weight, height, adjusted body mass index, duration of diabetes, treatment modality, and glycosylated hemoglobin A1c (HbA1c) levels of each patient were recorded.Results:As compared with the baseline, a significant improvement was noted in the behavior of FOH (P = .0001), worry (P = .0001), QoL (P = .002), HbA1c level (P = .008), and hypoglycemia (P = .023) at 3 months. Significant improvement was noted in the behavior (P = .0001), worry (P = .0001), QoL (P = .003), HbA1c level (P = .014), and hypoglycemia (P = .001) among the multiple-dose insulin injection–treated patients as compared with baseline. Significant improvement was noted in the behavior (P = .0001), worry (P = .0001), and hypoglycemia (P = .001) among the insulin pump–treated patients as compared with baseline. A positive correlation was recorded in the behavior (r = .47; P < .001), QoL (r = .70; P < .001), and the mean number of FGM scans. A negative correlation was recorded in the worry (r = −.43; P = .002), HbA1c level (r = −.58; P < .001), hypoglycemia (r = −.65; P < .001), and the mean number of FGM scans.Conclusions:The frequent use of FGM scanning reduced the frequency of hypoglycemia, HbA1c level, and worry and increased the behavior and QoL. As compared with self-testing by the conventional finger-pricking method, the use of FGM increased the frequency of self-testing and thus diabetes control.

Protocolo diagnóstico, tratamiento y seguimiento de la diabetes en el embarazo

IntroductionDiabetes is the metabolic disorder that is most often associated with pregnancy. Maternal and foetal morbidity and mortality decrease with adequate metabolic control and obstetric surveillance. EtiopathogenesisThe most characteristic physiological modification of glucose homeostasis in pregnancy is an increase in insulin resistance in 2nd and 3rd trimesters. Insulin secretion undergoes parallel changes. DiagnosisPregestational diabetes: standard criteria of the World Health Organization (WHO) or American Diabetes Association (ADA). Gestational diabetes: criteria of the National Diabetes Data Group (NDDG) as recommended by Grupo Español de Diabetes y Embarazo (GEDE). TreatmentNutrition therapy, physical activity and pharmacologic therapy according to each case. Pregestational type 1 diabetes: multiple-dose insulin injections (basal bolus) or insulin pump therapy. Pregestational type 2 diabetes and gestational diabetes: initiate insulin if glycemic goals are not achieved.

Simultaneous Use of Two External Subcutaneous Pumps Delivering Insulin and SYMLIN: Use of a Double-Pump System

The combination of insulin and an amylin mimetic is an option for diabetes treatment.1,2 The effectiveness of this modality has been established, but there is a limited amount of literature regarding the use of this combined treatment via continuous subcutaneous infusion by external pumps. A short 16-week trial of 10 patients studied the pharmacokinetics of pramlintide (SYMLIN®, Amylin Pharmaceuticals, LLC, San Diego, CA) in continuous subcutaneous infusion and found this modality to be safe and well tolerated.3 Treatment was initiated in a small study of 10 subjects (7 females and 3 males) with age range 24-69 years. There were 5 patients with type 1 diabetes and 5 with type 2 diabetes (duration of diabetes: 15-38 years). Patients were switched from conventional multiple-dose insulin injection therapy or oral hypoglycemic agents to the combination of insulin and SYMLIN via continuous subcutaneous infusion using two external pumps simultaneously. Treatment was continued over a period of 1-5 years. Hemoglobin A1c (HbA1c), total daily insulin, total daily SYMLIN, weight, and blood glucose levels were measured, with follow-up ranging from 1-5 years. Patients using the double-pump system showed an average reduction in HbA1c from 8.3% to 6.9%. Total daily insulin was reduced from an average of 147 to 96 units per day. SYMLIN dosages increased from an average of 35 units per day to 50 units per day (Figure 1). Weight reduction was noted, with an initial average of 132 to 500 lb, decreasing to 110 to 360 lb. Figure 1 Insulin dosage vs SYMLIN dosage over duration of study. Amylin conversion of units to micrograms: 1 unit = 6 μg. Patients were treated with basal SYMLIN 0.5-2.5 unit/h (3-15 μg). Meal bolus was 2.5-10 units (15-60 μg). All patients completed a satisfaction survey and expressed satisfaction with the treatment regimen but indicated their preference for a dual or multichamber device. They also noted that they would not return to conventional SYMLIN injections if given the choice. We conclude that continuous infusion of insulin and SYMLIN via a pump system is a viable and effective therapeutic option. In this small observational study, all patients showed improvement in metabolic and weight control over a period of 1-5 years. Further studies with a larger population and a control group are needed to empower these results.

Insulin pump therapy: closing the inequality gap

110 Nurse Prescribing 2011 Vol 9 No 3 adapted accordingly. Mimicking the natural production of insulin is complex, and the way insulin is delivered through insulin pump therapy is closer to this natural phenomenon than multiple-dose insulin injection therapy. Pumps can help when: regulation is not sufficient with multiple-dose insulin injection therapy; glucose levels are unpredictable; the patient experiences severe hypoglycaemia, or even fits. Experience has shown that the use of the pump in the latter case led to the patient no longer experiencing fits or severe hypoglycaemia.

Continuous subcutaneous insulin infusion and multiple dose insulin injections in Type 1 diabetic pregnant women: a case-control study

The aim of this study was to evaluate the effects of continuous subcutaneous insulin infusion (CSII) on glycemic control and pregnancy outcomes in Type 1 diabetic pregnant women. We retrospectively evaluated 42 subjects, 20 treated with CSII and 22 with multiple dose insulin injections (MDI). The two groups were comparable for age, pre-pregnancy BMI, and primiparous rate, whereas women in the CSII group showed a tendency toward a longer diabetes duration (p = 0.06). Pre-pregnancy diabetic retinopathy and/or nephropathy were present in nine women of CSII and three of MDI. In all women metabolic control improved during pregnancy, without differences between the two groups and at the end of gestation HbA1c was 6.3 +/- 0.6 in CSII and 6.1 +/- 1.1% in MDI. Moreover, there were no differences in weight gain, whereas insulin requirement resulted significantly (p = 0.009) lower in CSII than in MDI. We recorded only one severe hypoglycaemic episode in both groups. No cases of deteriorations of the chronic diabetic complications were observed. The delivery occurred at 36.4 +/- 2.2 weeks; birth weight, the rate of large for gestational age, and the parameters of foetal morbidity were similar in both groups. In conclusions, CSII and MDI are both effective in improving maternal glucose control and have both similar pregnancy outcomes.

Multiple-dose insulin injection therapy in patients with type 2 diabetes using a basal-bolus regimen, team management, and nutrition education

We determined the efficacy of basal-bolus insulin therapy delivered through team education and nutrition counseling formanagement of type 2 diabetes in 17 patients treated with a regimen of once-daily insulin glargine and either insulin aspart orlispro three times a day. They received written instructions and specific education about ‘basal-bolus’ insulin administration,use of a ‘forced-titration’ schedule for glargine dose adjustment, and calculation of rapid-acting pre-meal bolus insulin. Theaverage hemoglobin A1c level decreased from 8.7 ± 2.06% to 7.0 ± 1.07%, a significant reduction of 1.7% (p<0.05) over 3months or more. 7 patients (41%) reported improvement in hypoglycemic events. In conclusion, an intensive multidose basalbolusinsulin treatment using self-titration and flexibility through carbohydrate counting confers beneficial effects in patientswith type 2 diabetes, including better glycemic control and reduced hypoglycemia. These results are best achieved throughmulti-disciplinary patient care involving the nurse educator and dietician as part of a diabetes care team. (Int J DiabetesMetab 13:141-146, 2005)

Beneficial Effects of Continuous Subcutaneous Insulin Infusion in Older Patients with Long-Standing Type 1 Diabetes

To assess the effect of continuous subcutaneous insulin infusion (CSII) on glycemic control, hypoglycemia, and daily insulin requirements in five older patients with long-standing type 1 diabetes previously treated with multiple-dose insulin injections (MDII). We undertook a retrospective analysis of five older patients (three women and two men) with type 1 diabetes and a mean age of 66.4 years (range, 57 to 76). The mean duration of disease was 33 years (range, 18 to 49), and all patients had suboptimal glycemic control (glycosylated hemoglobin or HbA(1c) >8.0%), presence of microvascular complications, and unacceptably frequent hypoglycemia during MDII therapy. A diabetes care team monitored their clinical course after their treatment was changed to a CSII regimen. Data pertaining to HbA(1c), severe hypoglycemia, and insulin dose before and after conversion to CSII were compared with use of paired t tests. After initiation of CSII therapy, the mean HbA(1c) value decreased from 9.16% to 7.6% (P<0.0025), the rate of severe hypoglycemia decreased from 3.2 episodes to 0.4 episode per year (P<0.02), and the mean total daily insulin dose was reduced from 44.9 IU to 32.4 IU (P<0.05) during a mean duration of 12.6 months of CSII therapy. Insulin pump therapy can prove highly beneficial in older patients with type 1 diabetes by improving glycemic control, reducing hypoglycemic episodes and insulin dosage, and possibly increasing treatment satisfaction. These changes can potentially prevent morbidity and prove to be cost-effective. For implementation of pump conversion to be safe and successful, careful patient selection, proper education, and ongoing support through a comprehensive diabetes education and management program are imperative. Future reports of experience with CSII in elderly patients should help to elucidate its promising advantages in this patient population and provide guidelines for use.

New concepts and applications in the use of the insulin pump during pregnancy

Subcutaneous insulin infusion or insulin pump therapy has been advocated as an alternative to multiple dose insulin injections for nearly two decades. These devices provide insulin administration in a pattern which more closely resembles that of physiologic insulin release, a basal insulin infusion during the day and throughout the night with boluses given prior to meals. Because the number of patients using an insulin pump is increasing, it is likely the perinatologist will encounter women who are being treated with an insulin infusion pump or are considering this therapy. Insulin pump therapy requires that the patient be highly motivated and compliant. One of the most important criteria in selecting patients for this treatment is their willingness to test their capillary glucose levels 6 to 8 times each day. Interruption of the insulin infusion can produce hyperglycemia in any pump user. Should this occur in the pregnant patient, the likelihood of ketoacidosis developing is significantly greater. Ideally, insulin pump therapy should be initiated prior to pregnancy so that glucose control can be normalized, thereby reducing the risk for spontaneous abortion and fetal malformations. Gradually improving glucose control prior to pregnancy can reduce the likelihood of deterioration of retinopathy, which has been observed when poorly controlled pregnant patients rapidly become euglycemic. The published experience with the insulin pump has demonstrated that this therapy can achieve glucose control and perinatal outcomes comparable to that obtained with multiple-dose insulin injection therapy.