Number Of Insulin Injections Research Articles

Timing of insulin bolus in patients with type 1 diabetes: effect on glucose control and variability using CGMS

AbstractThe aim of this non‐randomised, pilot study was to examine the effect of insulin bolus injection timing on overall daily glucose control and glucose variability using a continuous glucose monitoring system (CGMS).Twelve patients with type 1 diabetes treated with either multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII), with HbA1c ≤7.5% (58mmol/mol), were connected twice to a CGMS for 72 hours. During period one the patients injected the insulin bolus before the meal and, during period two, after the meal. The variability of blood glucose (BG) was assessed by low BG indices (LBGI) and high BG indices (HBGI) – the measure of the variability of low and high BG readings. Their sum (LBGI + HBGI) gives the BG risk index (BGRI) – a measure of overall variability and deviations towards hypo‐ and hyperglycaemia.Six patients were on CSII and six on MDI. The number of meals, number of insulin injections and average BG were not different between the groups. LBGI and the number of hypoglycaemic events were not affected by the method of injection. BGRI were significantly higher for post‐meal injection, mainly due to increased hyperglycaemia (p=0.003). The increased HBGI and BGRI were more prominent in CSII (p=0.05). These differences were found for the 72‐hour variability but not when testing 2 hours post‐prandially.It was concluded that injecting insulin prior to the meal can reduce the overall glucose variability, and remains the preferred method of injection. Larger studies are needed in order to reinforce these results. Copyright © 2012 John Wiley & Sons.

Insulin analogs versus human insulin in type 2 diabetes

Oral hypoglycaemic agents become less effective as beta cell function declines. Thus many patients with type 2 diabetes will ultimately require treatment with insulin. There are two main approaches to starting insulin: (a) as a basal supplement with an intermediate to long-acting preparation (NPH, glargine or detemir) plus oral agents; (b) as a premixed insulin regimen. Almost all the studies have shown similar glucose control with both NPH and the new insulin analogs. Further analyses between these insulins have documented significant reductions in hypoglycaemia especially at night with the insulin analogs. The weight gain is an important issue in patients with diabetes. It appears that insulin detemir studies have reported weight neutrality or less weigh gain or even weight loss. However, most insulin glargine studies have reported a weight gain. On the other hand insulin analogs have the important disadvantage of high cost. It is important to take in to account all the above factors such as cost, weight gain, number of insulin injections and hypoglycaemia while prescribing insulin.

Independent factors associated with depression in type 1 diabetes mellitus

Diabetes has been associated with depression since Thomas Willis' work in 1684 (Rubin and Peyrot in Diabetes Metab Rev 18:173-175, 2002). The aim of this study is to identify social and clinical factors independently associated with depression in individuals with type 1 diabetes. We carried out a descriptive transversal study with 110 type 1 diabetes patients, administered a questionnaire and obtained demographical and diabetes-related data (number of years from diagnosis, initial admission at diagnosis, glycated hemoglobin, number of complications, insulin dose, number of insulin injections per day, admission for ketoacidosis or hypoglycemia at diagnosis, and specific diabetes complications such as nephropathy, retinopathy, peripheral neuropathy, coronariopathy, and amputation). Depressive symptoms were quantified using the Hamilton Score. We used T tests to investigate potential relations between the covariates and depression (Hamilton score). We concluded the following: as few as 10% of our patients had glycated hemoglobin under 7%; women had more symptoms of depression, and there are four independent factors associated with depression in individuals with type 1 diabetes mellitus: age, Graffar score, admission for ketoacidosis, and insulin dose.

Insulin Binding to Antibodies is a Risk Factor for Inexplicable Severe Hypoglycaemia in Children with Type-1 Diabetes Mellitus

Type-1 diabetic individuals differ with regard to both, the formation of circulating insulin antibodies, and the incidence of severe hypoglycaemia. To assess the association of insulin binding to antibodies with the incidence of severe hypoglycaemia. In a cross sectional study, 73 children with type-1 diabetes mellitus (median age 14 years, duration of diabetes 6 years) were investigated, 22 of whom had experienced severe hypoglycaemia during the past 18 months, and 51 had never experienced severe hypoglycaemia. Of the patients with severe hypoglycaemia 16 had experienced severe unexplained hypoglycaemias, and 6 had experienced severe hypoglycaemias which were explicable (by missed meals, unplanned physical exercise etc.). Insulin binding was measured in a blinded central laboratory by radioimmunoassay, and expressed as ratio bound/unbound insulin; a binding >15% was considered relevant insulin binding. A total of 38 patients displayed relevant insulin binding (17 of whom had experienced severe hypoglycaemia), and 35 patients did not (5 of whom had experienced severe hypoglycaemia; p=0.0055, Fisher's exact test). Patients with relevant insulin binding were younger (12.2 vs 14.5 years, p=0.006) than patients without relevant insulin binding. From the 16 patients with inexplicable severe hypoglycaemia, 15 displayed relevant insulin binding, compared to 2 of the 6 patients with explicable severe hypoglycaemia (p=0.009). The association of any severe hypoglycaemia, and of inexplicable severe hypoglycaemia, with relevant insulin binding was significant (odds ratio 4.8 (95%CI 1.5-15.2), and 22.1(95%CI 2.7-179.6), p<0.006). Patients with/without relevant insulin binding, or with/without severe hypoglycaemia, did not differ significantly regarding sex, duration of diabetes, number of insulin injections per day, HbA1c and C-peptide levels (ANOVA). Insulin binding to antibodies >15% appears to be a strong risk factor for inexplicable severe hypoglycaemias in type-1 diabetic children.

PREDICTIVE™– a global, prospective observational study to evaluate insulin detemir treatment in types 1 and 2 diabetes: baseline characteristics and predictors of hypoglycaemia from the European cohort

PREDICTIVEtrade mark (Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation) is a large, multi-national, observational study assessing the safety and efficacy of insulin detemir. We report the study design, population characteristics and baseline observations, including cross-sectional analysis, from 19 911 patients with type 1 or 2 diabetes. Patients with type 1 or 2 diabetes requiring basal insulin are prescribed insulin detemir and followed up for 12-52 weeks. Data on demographics, haemoglobin A(1c) (HbA(1c)), fasting glucose, within-subject fasting glucose variability and weight are collected from patient records (and/or recall for hypoglycaemia). A negative binomial distribution model is used to assess the influence of predictive/confounding variables on hypoglycaemic episodes in insulin-treated patients at baseline. Multi-factorial analysis of covariance is used to evaluate the association of the variables with current body weight and within-subject fasting glucose variability. Total hypoglycaemic episodes in the 4 weeks prior to study start were 47.5 per patient-year in patients with type 1 and 9.2 per patient-year in patients with type 2 diabetes. The frequency of hypoglycaemia in insulin-treated patients showed a significant, positive association with duration of diabetes, number of insulin injections and fasting glucose variability but was inversely related to HbA(1c), fasting glucose and body mass index. Weight showed a significant positive association with gender (male > female) and insulin dosage. Weight was also positively associated with fasting glucose variability in patients with type 1 diabetes, and age and number of injections in patients with type 2 diabetes. These baseline data showed that, in addition to the established relationship with intensive treatment and HbA(1c), frequency of hypoglycaemia was positively associated with fasting glucose variability. Follow-up data from PREDICTIVE will provide insights on insulin detemir in diabetes management.

Day-to-day glucose variability during pregnancy in women with Type 1 diabetes mellitus: glucose profiles measured with the Continuous Glucose Monitoring System.

To observe day-to-day variability in glucose levels in pregnant women with Type 1 diabetes using the Continuous Glucose Monitoring System (CGMS) and to assess the usefulness of continuous glucose measurements for adjustment of insulin treatment. A prospective observational study. The obstetrical outpatient clinic of the University Medical Centre Utrecht. Pregnant women with Type 1 diabetes mellitus. Thirty-one pregnant women with Type 1 diabetes used the CGMS for two consecutive days. Patients were classified in two groups (high vs low day-to-day variability) based on visual inspection of the glucose excursions. The relationship between day-to-day variability and the variables HbA(1c), maternal age and body mass index (BMI), duration of diabetes, number of self-monitored blood glucose levels, number of insulin injections, gestational age, nutrition, physical activity, White classification, living with children and method of insulin administration was determined. The two days of the first 20 CGMS measurements were separated and four physicians were asked to give recommendations on treatment adjustment for each separate day. Mean absolute difference (MAD) was calculated for each patient as measure of day-to-day variability. Seventeen patients (55%) were classified as having low (MAD 0.92-2.33 mmol/L) and 14 (45%) as having high day-to-day variability (MAD 2.41-6.12 mmol/L). Of the variables measured, only the relation between MAD and HbA(1c) was significant (r= 0.58, P= 0.001). The difference in recommendation on treatment adjustment between the days of the CGMS measurement ranged from 29% to 48%. This percentage was significantly higher in the high day-to-day variability group (48 vs 33%, P= 0.01). Day-to-day glucose variability is high and the treatment of pregnant women with Type 1 diabetes is a problem. Fine-tuning of insulin regimens based on two-day measurements with the CGMS is not advisable.

Searching for glycemic control in pediatric type 1 diabetes: A long way to go

Searching for glycemic control in pediatric type 1 diabetes: A long way to go

Combination oral agent and insulin therapy for type 2 diabetes mellitus.

Type 2 diabetes is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. Over time, there is progressive beta-cell failure. Combination oral and insulin therapy aims at treating both the defects in underlying pathophysiology and replacing insulin once beta-cell failure has occurred. Combination therapy is routinely used in the management of diabetes to reduce hemoglobin A1c, weight gain, and the number of insulin injections a patient requires. This article examines the effects of combining various oral agents with insulin on glycemic control, hypoglycemia, weight gain, and nonglycemic benefits of these combinations.

Quality of care of patients with diabetes mellitus living in a rural area of Germany

In a population based study the quality of diabetes care of insulin-treated diabetic patients aged 16 to 60 years and living in a rural area was studied. The parameters of metabolic control as well as the incidence of acute complications (severe hypoglycemia with the need of glucose or glucagon injection, ketoacidosis with hospital admission) were assessed by examination and with a standardized questionnaire in 81% of the target population (type-1/type-2-diabetic patients: n = 25/33). Also, in all the patients diabetic long-term complications (retinopathy, nephropathy, amputations of the lower extremities) were examined. 76% of the patients with type-1-diabetes and 91% of the patients with type-2-diabetes mellitus completed standardized questionnaires to assess quality of life and treatment satisfaction. In type-1-diabetic patients HbA1c was 9.38 +/- 1.6%. In type-2-diabetic patients it was 9.53 +/- 1.91%. None of the patients examined was regularly treated by a specialized physician/diabetologist. The goal of metabolic control, a HbA1c value below 7.2%, was reached only by 4% of the patients with type-1-and 12% of the patients with type-2-diabetes mellitus. In multivariate analysis the most important factor associated with HbA1c was in type-1-diabetic patients female sex (R-squared = 0.17, c = 0.38, p = 0.059); in patients with type-2-diabetes mellitus it was the number of insulin injections per day (R-squared = 0.37, c = 0.19, p = 0.0096). All other factors investigated in the model (diabetes duration, insulin dosage/kg body weight, frequency of blood- or urine-glucose self-monitoring/week, body mass index, educational level) showed no significant associations. Quality of life and treatment satisfaction of the patients were good and comparable to other trials. Out of other studies there is evidence for better metabolic control in patients regularly treated by specialized physicians/diabetologists and in patients who participated in structured treatment and teaching programs. These features must be the main goals of treatment for all patients with diabetes mellitus.

How to Apply the Experience from the Diabetes Control and Complications Trial to Children and Adolescents?

The Diabetes Control and Complications Trial (DCCT) taught us to set target blood glucose (BG) and glycohaemoglobin (GHb) goals, to ensure safety regarding hypogly-caemia, to be flexible with insulin and meal planning and to offer frequent contact with diabetes educators, dieticians, psychologists and social workers as well as with diabe-tologists skilled in intensified management. Insulin dosage should be individualized based upon frequent BG monitoring results. Co-ordinated multidisciplinary health care teams provide optimum problem-solving rather than disaster control working with children, adolescents and their families. The patient and the family should form the central core of the diabetes team with outpatient follow-up every month and frequent telephone contact between visits. GHb should be obtained at least every 1–2 months to provide feedback as based on the DCCT intensified treatment cohort. Insulin lispro helps minimize hypoglycaemia and makes insulin administration more convenient and timely. Barriers to improvement should be identified: learning problems, concomitant significant illnesses (epilepsy, coeliac and thyroid disease, asthma) and family problems. Ensure age-appropriate transfer of self-care but continue adult supervision. Educate, motivate and re-educate. Meal planning includes not only carbohydrate counting but also maintaining normal lipids and energy needs for growth and development as well as strategies for activity compensation and hypoglycaemia prevention. Consideration of protein restriction may be required in adolescents with microalbuminuria. Individualized multidose insulin algorithms allow reactive (corrective) decisions based upon capillary BG results plus proactive (anticipatory) decisions to compensate for expected BG changes from changes in activity, food and/or illness using a multidose insulin schedule. The number of insulin injections does not define an intensified insulin treatment programme but rather the ability to target and achieve near-normal BG values as often as possible - without severe episodes of hypoglycaemia. Self BG monitoring is a key to success. Long-term monitoring should include not only frequent GHb but also at least annual fasting lipids, thyroid functions and microalbuminuria as well as dilated retinal exams, blood pressure, growth charting and Tanner staging.

Longitudinal patterns of glycemic control and diabetes care from diagnosis in a population-based cohort with type 1 diabetes. The Wisconsin Diabetes Registry.

Glycosylated hemoglobin is an indicator of long-term glycemic control and a strong predictor of diabetic complications. This paper provides a comprehensive description of glycemic control (total glycosylated hemoglobin (GHb)) up to 4.5 years duration of diabetes by age, duration, and sex in a population-based cohort (n = 507) aged less than 20 years followed from diagnosis of Type 1 diabetes in Wisconsin during 1987-1994 Important aspects of demographics and diabetes care are described to allow comparison with other populations. Since large variations between laboratories are known to exist in the measurement of GHb, levels are also interpreted relative to the frequency of short-term complications. GHb increased after diagnosis, but leveled off after 2-3 years. Peak GHb values occurred in the age group 12-15 years. The within-individual standard deviation in GHb between tests, adjusted for age and duration was 1.6%. The mean GHb at last testing was 11.3%, with a standard deviation across individuals of 2.9%. The majority (74%) of individuals saw a diabetes specialist at least once. The mean number of insulin injections per day increased from 2.2 to 2.5 across the 4.5-year duration, and the insulin dose increased from 0.6 to 0.9 units per day per kg body weight. Despite the quite satisfactory level of care, 38% of subjects had GHb levels associated with significant short-term complications.

Young-Adult Perspectives of Insulin-Dependent Diabetes

The purpose of this study was to document the self-care behaviors of patients with type I diabetes, identify their concerns about having diabetes, and measure their level of control (HbA1c). A 20-point questionnaire was mailed to 105 young adults with type I diabetes. Fifty-nine (56%) returned the questionnaire (33 males, mean age 23.2 years; 26 females, mean age 22.7 years). Duration of diabetes was 5 months to 25 years (mean = 11.28 years). HbA1c range was 5% to 13.9% (mean = 7.85%, normal < 6.6%). Sixty-eight percent performed at least one blood glucose test per day and 12% reported not testing at all. The number of insulin injections per day ranged from 2 to 5, and 83% regularly adjusted their insulin dose. Confidence in adjusting insulin was not related to duration of diabetes, age, or sex. Insulin manipulation to control weight was reported by 38% (24 females, 2 males). The long-term complications they were concerned about were eye disease (35%), pregnancy and childbirth (27%), hypoglycemia (13%), and loss of independence (5%). Hypoglycemia was always recognized by 35%, although 50% sometimes confused it with stress, tiredness, and high blood glucose. All subjects reported that hypoglycemia affected their lifestyle.

Symptomatic Hypoglycaemia in Childhood Diabetes: A Population‐Based Questionnaire Study

The occurrence of severe and mild hypoglycaemic attacks and their symptoms and signs were studied in 92 insulin-dependent diabetic children, 7-18 years old. A questionnaire was distributed to all families and they were interviewed by an experienced nurse. Severe attacks, for which the help of an adult was needed, were reported by 44% of the children during a 12-month period. Thirty-seven per cent of the attacks occurred in the mornings, most often attributed to extra physical exercise, but equally often without any obvious cause. They were more common in children with strict blood glucose control measured as HbA1c. Fast-acting carbohydrates, given by parents, relieved the attack in most children, but 15% needed a glucagon injection and 12% intravenous glucose. In all, 16% were admitted to hospital. Mild events occurred in 97% of the children, at least once per week in 53% of the children, and were not related to blood glucose control. They were often attributed to extra physical exercise and occurred mainly between breakfast and lunch. Initial symptoms were tremor and hunger; during the whole event tremor and sweating were most common. Parents noted pallor as the most common sign. The frequency of severe or mild attacks could not be correlated to the age of the child, duration of diabetes, daily dose or number of insulin injections.

Metabolic control in 131 juvenile-onset diabetic patients as measured by HbA1c: relation to age, duration, C-peptide, insulin dose, and one or two insulin injections.

Glycosylated hemoglobin A (HbA1c), considered to reflect long-term metabolic control of diabetes, was analyzed in 131 patients, aged 2 5/12-19 6/12 yr, with juvenile-onset diabetes. Using stepwise multiple regression HbA1c, fasting blood glucose and plasma 3-hydroxybutyrate were analyzed as dependent variables versus independent variables such as age of the patients, duration of the disease, level of plasma immunoreactive C-peptide (IRCP), insulin dose, and number of insulin injections (one or two) per day. HbA1c was inversely related only to IRCP concentration. A low but significant, positive correlation was found between HbA1c and the duration of diabetes. Stepwise addition of the other independent variables did not further increase the fraction of explained variance. HbA1c was also correlated with a subjective rating score of the metabolic control performed by the treating physician. Fasting plasma glucose was significantly related to HbA1c but not to any of the independent variables. Fasting 3-hydroxybutyrate showed an inverse correlation to the age of the patient. The present study showed that in juvenile-onset diabetic patients, endogenous insulin secretion as reflected by IRCP was the factor best correlated with a low level of HbA1c. After the cessation of endogenous insulin secretion, there is a progressive deterioration of metabolic control and multiple injections of insulin rather than one or two per day may be needed to reach optimal control in the patients.

Conditioning insulin effects.

It has previously been demonstrated that after a number of insulin injections in rats, an injection of a placebo leads to an elevation in blood sugar. It has been suggested that this apparent conditioned compensatory response is an artifact resulting from stressing the subject (when large doses of insulin are used) or represents a nonassociative phenomenon (when small doses of insulin are used). These two suggestions were rejected on the basis of the results of Experiments 1 and 2, respectively. Experiments 3 and 4 demonstrated that although the behavioral effects of insulin can be conditioned to the injection procedure, such conditioned insulinlike behaviors (contrary to suggestions of many investigators) are not mediated by a pypoglycemic state.