Bolus Insulin Therapy Research Articles

Observational 6-Month Open-Label Study of Japanese Type 2 Diabetes Patients Switching from NPH Insulin to Insulin Detemir in Basal—Bolus Regimen: 23rd Article of the Japan Diabetes Clinical Data Management Study Group (JDDM23)

Glycaemic control is critical to prevent diabetic complications and mortality. This 6-month, open-label, observational study assessed the efficacy and safety of switching Japanese patients with type 2 diabetes from neutral protamine Hagedorn (NPH) insulin to insulin detemir. Patients with type 2 diabetes (n = 126) receiving basal-bolus insulin therapy with NPH insulin plus rapid-acting insulin analogues were recruited. NPH insulin was replaced with insulin detemir for 6 months. Glycosylated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), daily glucose levels and hypoglycaemia were monitored. Nocturnal quality of life was assessed by insulin therapy related quality of life at night questionnaire. HbA(1c), FPG and body weight were all significantly reduced after treatment with insulin detemir for 6 months, without increasing severe hypoglycaemia. Insulin dose increased significantly over the same time. There were significant improvements in overall nocturnal quality of life, as well as well-being. Treatment with insulin detemir for 6 months resulted in substantial benefits, including reduced HbA(1c), FPG and body weight, and improvements in nocturnal quality of life, without increasing hypoglycaemia.

U-500 Insulin as a Component of Basal Bolus Insulin Therapy in Type 2 Diabetes

Changes in hemoglobin A1c (A1C), weight, and total daily insulin dose (TDD) were investigated following initiation of insulin U-500 (U500) alone or as part of a basal/bolus insulin (BBI) regimen. Records of patients with type 2 diabetes who were prescribed U500 were retrospectively reviewed. Logistic regression analysis was used to investigate relationships between changes in A1C and use of U500 alone or as BBI. Twelve patients were identified as using U500 alone (n=2) or in combination with long-acting (LAI) (n=7) or rapid-acting (RAI) (n=3) insulin. Reductions in A1C (9.5% at baseline vs. 7.7% at 6-9 months, P<0.0001) and increases in weight (128.8±32.7 vs. 131.5±31.3 kg, P<0.014) and TDD (260±111 to 333±106 units/day, P<0.0002) were observed. Concurrent use of LAI or RAI with U500 did not predict improvements in A1C. U500 resulted in improvements in A1C and weight gain and increased TDD when used alone or as part of combination insulin therapy. Further investigations to define the optimal use of U500 are recommended.

Effect of Miglitol as an Add-On to Bolus Insulin on Postprandial Glycemic Excursions in Type 2 Diabetes Patients Assessed by Continuous Glucose Monitoring

We compared the effects of miglitol as an add-on to bolus insulin and dose-intensified bolus insulin on postprandial glycemic excursions by continuous glucose monitoring (CGM). The glucose levels of 21 type 2 diabetes patients admitted for glycemic control were monitored for three consecutive days by CGM after stable glycemic control was achieved with bolus or basal-bolus insulin therapy. During the 3-day period, bolus insulin administration was continued in 11 patients on Day 1; the dose of bolus insulin in these patients was increased by 2 U before each meal on day 2, and on day 3, 50 mg of miglitol was administered before each meal in addition to the initial dose of bolus insulin given on Day 1. In the remaining 10 patients, the order of administration on Day 2 and Day 3 was reversed. Of the glycemic fluctuations observed during the 24-h period, postprandial glycemic excursions showed a greater reduction during treatment with dose-intensified bolus insulin and during treatment with miglitol plus bolus insulin than during treatment with bolus insulin alone; however, miglitol plus bolus insulin treatment had a more potent effect than treatment with dose-intensified bolus insulin on reducing postprandial glycemic excursions immediately after meals. Changes in area under the curve (ΔAUC) occurring within 1 h and 2 h after each meal were significantly smaller during treatment with miglitol plus bolus insulin than during treatment with dose-intensified bolus insulin, whereas ΔAUC within >2 h after each meal, except dinner, was significantly greater during treatment with miglitol plus bolus insulin than during treatment with dose-intensified bolus insulin. Our findings suggest that miglitol as an add-on to bolus insulin in patients with type 2 diabetes may be one of the beneficial therapeutic options that provides a more rigorous postprandial glycemic control without increasing the risk for hypoglycemia before the next meal.

Algorithms for Intravenous Insulin Delivery

This review aims to classify algorithms for intravenous insulin infusion according to design. Essential input data include the current blood glucose (BG(current)), the previous blood glucose (BG(previous)), the test time of BG(current) (test time(current)), the test time of BG(previous) (test time(previous)), and the previous insulin infusion rate (IR(previous)). Output data consist of the next insulin infusion rate (IR(next)) and next test time. The classification differentiates between "IR" and "MR" algorithm types, both defined as a rule for assigning an insulin infusion rate (IR), having a glycemic target. Both types are capable of assigning the IR for the next iteration of the algorithm (IR(next)) as an increasing function of BG(current), IR(previous), and rate-of-change of BG with respect to time, each treated as an independent variable. Algorithms of the IR type directly seek to define IR(next) as an incremental adjustment to IR(previous). At test time(current), under an IR algorithm the differences in values of IR(next) that might be assigned depending upon the value of BG(current) are not necessarily continuously dependent upon, proportionate to, or commensurate with either the IR(previous) or the rate-of-change of BG. Algorithms of the MR type create a family of IR functions of BG differing according to maintenance rate (MR), each being an iso-MR curve. The change of IR(next) with respect to BG(current) is a strictly increasing function of MR. At test time(current), algorithms of the MR type use IR(previous) and the rate-of-change of BG to define the MR, multiplier, or column assignment, which will be used for patient assignment to the right iso-MR curve and as precedent for IR(next). Bolus insulin therapy is especially effective when used in proportion to carbohydrate load to cover anticipated incremental transitory enteral or parenteral carbohydrate exposure. Specific distinguishing algorithm design features and choice of parameters may be important to establish freedom from hypoglycemia, eliminate the need for administration of concentrated dextrose during euglycemia, control variability within the treatment course of individual patients, achieve adaptability to differing blood glucose targets, and minimize variability of glycemic control between treatment courses of different patients or patient populations. Areas for future work include the reduction of nursing burden, the development of a theory that will account for lag time of interstitial monitoring and pharmacodynamic delay of insulin action, and management strategies for the narrow euglycemic range. It is hoped that hypoglycemia and variability of control will become negligible problems, and that fear of hypoglycemia no longer will deflect investigators and caregivers from providing optimal glycemic management.

Serum Glucose Changes During Insulin Therapy in Pediatric Patients With Diabetic Ketoacidosis

There are limited data on which to base insulin dosing schemes for diabetic ketoacidosis (DKA). The goal of therapy is to avoid excessive decreases in serum glucose (greater than 100 mg/dL/h) because of the risks of rapid changes in serum osmolarity and the potential risk of cerebral edema. We retrospectively reviewed the therapy of DKA in pediatric patients admitted to our Pediatric Intensive Care Unit over the past 10 years. There were 35 patients who received IV bolus insulin therapy (0.08 to 1.6 units/kg, 0.24 +/- 0.27 units/kg). The serum-glucose decrease was less than or equal to 100 mg/dL in 10 patients, 101 to 200 mg/dL in 13 patients, 201 to 300 mg/dL in 8 patients, 301 to 400 mg/dL in 2 patients, and more than 500 mg/dL in 2 patients. In patients who received 0.05 to 0.1 units/kg of insulin as a bolus dose, the decrease in serum glucose was greater than 100 mg/dL in 5 of 11 patients. An insulin infusion was administered to 91 patients. During the 243 hours of insulin infusion therapy, the decline in serum glucose was 0 to 100 mg/dL during 162 hours, 101 to 200 mg/dL during 49 hours, 201 to 300 mg/dL during 8 hours, and more than 300 mg/dL during 3 hours. Of the 193 hours of 0.05 to 0.1 units/kg/h insulin administration, there were 47 hours (24%) during which the serum-glucose decrease was greater than 100 mg/dL. Of the 21 hours of insulin administration at less than 0.05 units/kg/h, there was 1 hour (4.8%) where the serum-glucose decrease was greater than 100 mg/dL (P = 0.05 vs. insulin infusion at 0.05 to 0.1 units/kg/h). Commonly used insulin dosing regimens of a bolus of 0.1 units/kg followed by an infusion of 0.05 to 0.1 units/kg/h frequently resulted in a decrease in serum glucose of greater than 100 mg/dL/h. Prospective trials are needed to more accurately define appropriate insulin dosing regimens for pediatric patients with DKA.

V-Go™—A Novel Device for Delivering Basal–Bolus Insulin Therapy to Patients with Type 2 Diabetes Mellitus

V-Go™—A Novel Device for Delivering Basal–Bolus Insulin Therapy to Patients with Type 2 Diabetes Mellitus

The lipid spectrum of erythrocyte membranes in children with diabetes mellitus

The present study was undertaken to examine the lipid spectrum of erythrocytic membranes and serum in children and adolescents with type 1 diabetes mellitus (DM-1) during pathogenetic therapy in relation to the duration of the disease, its severity, and the presence of vascular events. Ninety-nine patients with DM-1 and 40 healthy children of the same age were examined. The patients were on basic bolus insulin therapy. In children, DM-1 was ascertained to be accompanied by not only atherogenic serum lipid metabolic disturbances (the elevated levels of total cholesterol, triglycerides, low- and very low-density lipoprotein cholesterol), but also by the impaired lipid spectrum of erythrocytic membranes (reductions in the level of total lipids and the fraction of phosphatidylcholine (PC) with an increase in the level of fractions of tysophosphatidylcholine and phosphaUdylinositol; elevated levels of saturated fatty acids and decreased levels of unsaturated fatty acids in the fractions of PC and phosphatidylethanolamlne; the enhanced microviscosity of deep membranous layers and the modified outer membranous ones). Complex basic therapy resulted in incomplete normalization of the study parameters of the lipid spectrum of serum and erythrocytic membranes in DM complicated by microangiopathies, which requires optimization of conventional therapeutic regimens.

Optimal insulin treatment for patients with type 2 diabetes: Basal or prandial insulin supplementation?

During the natural course of type 2 diabetes (T2D), insulin therapy is needed in order to maintain appropriate glycaemic control in a substantial part of patients. Although the definition theoretically is arbitrary, prandial and basal insulin could be used for insulin supplementation in clinical practice. To improve both prandial and basal insulin supplementation, short- and long-acting insulin analogues were recently developed. Clinical studies indicated that better prandial glucose control could be achieved by using short-acting insulin analogues, such as insulin lispro insulin, insulin aspart and glulisine than that observed by treatment with regular human insulin. Using new long-acting insulin analogues such as glargine or detemir, the risk of hypoglycaemia, especially nocturnal, could be decreased as compared with NPH insulin treatment. It is obvious that adequate prandial and basal insulin supplementation and nearly physiological insulin replacement could be carried out by using basal–bolus insulin therapy. Nevertheless, patients with T2D and stable lifestyle, or those who are unwilling to perform multiple daily insulin injections and blood glucose readings could sufficiently be treated by using premix human insulin preparations or more recently, by premix insulin analogues. Given the importance of clinical benefits of short-acting, long-acting and premix insulin analogues, the long-term effects of treatment with these relatively new insulin preparations are yet to be determined. Instead of the question whether basal or prandial insulin supplementation is more critical, the mode of treatment providing appropriate basal and prandial insulin supplementation is of importance. Using optimal insulin supplementation, all components of glucose triad (fasting glucose, postprandial glucose, HbA 1c) should be targeted by proper management of patients with T2D.

The development of non-insulin-dependent diabetes after total body irradiation and bone marrow transplantation in adolescence: a case report and literature review

A 6-yr-old-child received total body irradiation (TBI) and bone marrow transplantation (BMT) for relapsed acute lymphocytic leukemia. Nine years later, he developed diabetes mellitus (DM). He was started on basal bolus insulin therapy. Islet cell and anti-GAD antibodies were negative. Insulin and C-peptide levels were elevated consistent with insulin resistance (IR), even though his body mass index (BMI) was only 19.5. Hepatocyte nuclear factor (HNF-1alpha) mutation was not detected. Insulin was stopped and hemoglobin Alc (HbA1c) stabilized at 6.5% on gliclazide 40 mg/day. TBI has rarely been associated with IR and the development of diabetes. These patients can be managed with oral hypoglycemic agents and do not necessarily require insulin. Patients who received BMT and TBI may require long-term monitoring of glucose and lipid metabolism.

Enhancement of serum lipoprotein lipase mass levels by intensive insulin therapy

We previously reported that lipoprotein lipase mass level in preheparin serum (preheparin LPL mass) was significantly lower in type 2 diabetes mellitus compared to healthy subjects and increased by conventional insulin therapy using NPH (intermediate-acting) insulin. The aim of this study was to investigate the effects of intensive insulin therapy on preheparin LPL mass. Thirty-two subjects (total group) with type 2 diabetes receiving treatment by NPH insulin injection twice a day in the morning and evening were switched to basal bolus insulin (BBI) therapy (fast-acting insulin after each meal and NPH insulin before bedtime). In 14 subjects, the total daily insulin dose was not change after switching to BBI therapy (iso-dose group). After 3 months of BBI therapy, preheparin LPL mass increased significantly from 47 to 56 ng/ml in total group. Glycosylated hemoglobin and serum triglyceride levels decreased significantly, and high-density lipoprotein-cholesterol increased significantly. Low-density lipoprotein levels did not changed but increase in size was suggested by PAG disc electrophoresis. Similar changes were observed in the iso-dose group. These results suggest that BBI therapy enhances preheparin LPL mass, accompanied by antiatherogenic changes in glucose and lipid metabolism.