Premeal Injections Research Articles

Effects of leonardite and succimer treatment on enzyme activity in rats exposed to lead acetate

The study aimed to research in vivo changes in the enzyme activity of the blood and liver of laboratory rats under continuous exposition to a moderate dose of lead acetate while receiving succimer together with humic feed additive madden out of leonardite. Two-month-old white rats were used to assess the detoxifying properties of the humic compounds leonardite and lignite. To conduct the study, a total of 32 male laboratory rats were divided into four groups, each consisting of eight animals, using the analog pair approach. Rats received a pre-meal injection of lead acetate at a dose of 7 mg/100 g of animal weight (1/110 LD50) using a veterinary feeding needle. Humic feed additives were supplied to animals by creating solutions from leonardite at a dosage of 18 mg/kg depending on the active ingredient. Succimer was prescribed in an amount of 30 mg/kg, previously dissolved in apple juice using a feeding tube 3 hours after eating one time in a day. Upon analyzing the collected data, it can be deduced that the treatment involving succimer and the humic-based feed additive leonardite alongside lead acetate poisoning yielded improved protein metabolism and activity of enzymes in poisoned rats. Notably, in all statistically significant instances (P < 0.05) of improvement in indicators among animals in that research group, the numerical values closely approximated those of intact animals. The key distinction between treating animals with succimer alone and the combination of succimer and leonardite primarily manifested in alterations in the activity of liver enzymes involved in the antioxidant system such as: catalase, superoxide dismutase, glutathione peroxidase.

Effect of Postmeal Fast-Acting Insulin Aspart Injection on the Frequency of Hypoglycemia among Pre-School Children with Type 1 Diabetes: An Open-Label, Cross-Over, Randomized Control Trial.

To study the effect of postmeal Fast-acting insulin Aspart (Fiasp®) on the frequency of hypoglycemia compared to premeal injection among preschool children with type 1 diabetes. A single-center trial was conducted among 65 pre-school children (6 mo to 6 y) with Type 1 diabetes for at least 6 mo, on multiple daily insulin injections. Children were randomized to receive their meal bolus postmeal or premeal for the first 3 mo, followed by cross-over at 3 mo. The two groups were compared at the end of 6 mo for the change in frequency of hypoglycemia and hyperglycemia, HbA1c, glycemic variability, and parental satisfaction. Ten children (5 in each group) underwent pharmacokinetic studies. The trial was approved by Institutional Ethics Committee and registered with the Controlled Trial Registry of India vide no CTRI/2020/10/028750. Fifty-four children completed the study, with 27 children in each group. There were no significant differences in the frequency of clinical (p = 0.921), severe (p = 0.167) or serious (p = 0.753) hypoglycemia in the two groups. There were no differences in secondary outcome parameters and pharmacokinetics. The premeal or postmeal injection ofFiasp® does not affect the frequency of hypoglycemia or other glycemic control parameters among pre-school children with Type 1 diabetes. The trial is registered with the Controlled Trial Registry of India vide no CTRI/2020/10/028750.

Effects of leonardite and lignite on blood parameters in rats exposed to lead acetate

The study aimed to research in vivo changes in the hematological and biochemical parameters of laboratory rats' blood when they were continuously exposed to a moderate dose of lead acetate while receiving humic feed additives made of leonardite and lignite. Two-month-old white rats were used to assess the detoxifying properties of the humic compounds leonardite and lignite. The analog pair approach was used to create four groups of eight animals from 32 male laboratory rats for the study. Rats received a pre-meal injection of lead acetate at a dose of 7 mg/100 g of animal weight (1/110 LD50) using a veterinary feeding needle. By creating solutions from lignite and leonardite at a dosage of 18 and 25 mg/kg depending on the active ingredient, humic feed additives were supplied to animals. It has been demonstrated that lignite- and leonardite-based feed additives may affect the morphological parameters of lead acetate-treated rats' blood, including hemoglobin, hematocrit, erythrocyte, and platelet count. These parameters were very near to the levels of the intact rats, which suggests that these humic feed additives may have an anti-anemic impact. The effects of feed additives from leonardite and lignite on laboratory rats in groups that were also exposed to a toxic agent for all 21 days of the experiment led to the normalization of markers of the state of protein metabolism in the group of intact animals (serum protein, albumins, urea, creatinine), particularly activity of the enzyme’s aspartate aminotransferase and alanine aminotransferase. As one of the most crucial indicators of lipid metabolism together with cholesterol, the concentration of triglycerides was slightly lower in the humic substances treated groups than in the intact animals. It was discovered that using a feed supplement made from leonardite in a dosage of 18 mg/kg, which contained more fulvic acids than lignite, led to more favorable blood test results in the research group.

Improved Postprandial Glucose Control Using the InsuPad Device in Insulin-Treated Type 2 Diabetes: Injection Site Warming to Improve Glycemic Control.

Delays in the time-action profiles of premeal boluses of rapid-acting insulin analogs contribute to early postmeal hyperglycemia in patients with diabetes. We tested whether applying local heat to skin around the injection site to increase the rate of insulin absorption reduces postprandial hyperglycemia in patients with type 2 diabetes. Fourteen patients with type 2 diabetes (4 females; age 61.6 ± 8.4 years, HbA1c 8.42 ± 1.13%; BMI 29.10 ± 5.61 kg/m(2)) on intensified insulin therapy underwent 5-hour meal tolerance tests (MTTs) with a standardized liquid meal after an overnight fast on 2 study days. Subjects injected 0.2 U/kg of insulin aspart or lispro subcutaneously into the abdominal skin on both days with and without the use of the InsuPad device. Following the premeal bolus injection of rapid-acting insulin analog, infusion site warming led to a rise in plasma insulin levels to peak concentrations that were significantly earlier than without skin warming (mean ± SD 52 ± 26.7 vs 80 ± 51.3 minutes, P < .005) as well as increase in plasma insulin levels during the first hour after injection (mean ± SD 63.5 ± 32.7 IU vs 48.0 ± 25.0 uU.min/ml, P = .019). As a result, the area under the curve of the postprandial glucose excursion during the first 2 hours (the primary study outcome) and the entire 5 hours after the meal were significantly reduced (P = .007 and P = .03, respectively) with skin warming around the injection site. Use of the InsuPad to increase the rate of insulin absorption provides an effective means to achieve better control of postmeal glucose excursions in type 2 diabetic patients receiving premeal injections of rapid-acting insulin analogs.

Switching to multiple daily injection therapy with glulisine improves glycaemic control, vascular damage and treatment satisfaction in basal insulin glargine‐injected diabetic patients

Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established. Fifty-nine diabetic patients (49 type 1 and 10 type 2; 52.9 ± 13.3 years old) whose blood glucose levels were uncontrolled (HbA1c > 6.2%) by combination treatment of basal insulin glargine with multiple daily pre-meal injections of bolus short-acting insulin [aspart (n = 19), lispro (n = 37) and regular human insulin (n = 3)] for at least 8 weeks were enrolled in this study. We examined whether glycaemic control and vascular injury were improved by replacement of short-acting insulin with glulisine. Patient satisfaction was assessed with Diabetes Treatment Satisfaction Questionnaire. Although bolus and basal insulin doses were almost unchanged before and after replacement therapy, switching to glulisine insulin for 24 weeks significantly decreased level of HbA1c , advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), monocyte chemoattractant protein-1 (MCP-1) and urinary albumin excretion. In multiple stepwise regression analysis, change in MCP-1 values from baseline (ΔMCP-1) was a sole determinant of log urinary albumin excretion. ΔAGEs and ΔsRAGE were independently correlated with each other. The relationship between ΔMCP-1 and ΔsRAGE was marginally significant (p = 0.05). Replacement of short-acting insulin by glulisine significantly increased Diabetes Treatment Satisfaction Questionnaire scores. Our present study suggests that combination therapy of glargine with multiple daily pre-meal injections of glulisine might show superior efficacy in controlling blood glucose, preventing vascular damage and improving treatment satisfaction in diabetic patients.

Effect of Pramlintide on Prandial Glycemic Excursions During Closed-Loop Control in Adolescents and Young Adults With Type 1 Diabetes

OBJECTIVEEven under closed-loop (CL) conditions, meal-related blood glucose (BG) excursions frequently exceed target levels as a result of delays in absorption of insulin from the subcutaneous site of infusion. We hypothesized that delaying gastric emptying with preprandial injections of pramlintide would improve postprandial glycemia by allowing a better match between carbohydrate and insulin absorptions.RESEARCH DESIGN AND METHODSEight subjects (4 female; age, 15–28 years; A1C, 7.5 ± 0.7%) were studied for 48 h on a CL insulin-delivery system with a proportional integral derivative algorithm with insulin feedback: 24 h on CL control alone (CL) and 24 h on CL control plus 30-μg premeal injections of pramlintide (CLP). Target glucose was set at 120 mg/dL; timing and contents of meals were identical on both study days. No premeal manual boluses were given. Differences in reference BG excursions, defined as the incremental glucose rise from premeal to peak, were compared between conditions for each meal.RESULTSCLP was associated with overall delayed time to peak BG (2.5 ± 0.9 vs. 1.5 ± 0.5 h; P < 0.0001) and reduced magnitude of glycemic excursion (88 ± 42 vs. 113 ± 32 mg/dL; P = 0.006) compared with CL alone. Pramlintide effects on glycemic excursions were particularly evident at lunch and dinner, in association with higher premeal insulin concentrations at those mealtimes.CONCLUSIONSPramlintide delayed the time to peak postprandial BG and reduced the magnitude of prandial BG excursions. Beneficial effects of pramlintide on CL may in part be related to higher premeal insulin levels at lunch and dinner compared with breakfast.

Postprandial Platelet Activation Is Related to Postprandial Plasma Insulin Rather Than Glucose in Patients With Type 2 Diabetes

Postprandial hyperglycemia is associated with platelet activation. We thus investigated if meal-induced platelet activation could be attenuated by meal insulin. A randomized, double-blind, cross-over study was performed to compare postprandial platelet activation after premeal injections of placebo or insulin aspart (0.1 and 0.2 units/kg) in 18 patients with type 2 diabetes mellitus (T2DM). Platelet activation was assessed by flow cytometry, without and with stimulation by the thromboxane analog U46619 or ADP. Measurements were before and after premeal blood glucose standardization (to 6–7 mmol/L by insulin infusion, if needed) and at 90 min after the meal. Premeal insulin reduced postprandial hyperglycemia by 2–3 mmol/L compared with placebo. Postmeal insulin levels were doubled with placebo and further elevated with insulin injections. The standardized meal enhanced U46619-induced platelet P-selectin expression by 23% after placebo; this response was more than doubled after premeal insulin. U46619-induced fibrinogen binding was unchanged after meal intake with placebo but was markedly enhanced (by ∼50–60%) after premeal insulin. Postprandial platelet activation correlated positively to postprandial insulin levels and inversely to glucose levels. Premeal insulin infusion was also associated with platelet activation. Our results suggest that postprandial insulin rather than glucose accounts for postprandial platelet activation in T2DM patients.

The Treatment for Anti-insulin Antibody-mediated Immunological Insulin Resistance

Anti-insulin antibody is sometimes observed in diabetic patients treated by exogenous insulin. Anti-insulin antibody induces immunological insulin resistance and poor glycemic control. We previously reported a type 1 diabetic patient who showed severe insulin resistance due to insulin analog aspart-induced anti-insulin antibody [1]. He has been treated by using insulin aspart and insulin glargine. We treated him with the use of the newest insulin analog, insulin glulisine. This treatment significantly ameliorated his glycemic control and anti-insulin antibody 125I-binding rate, suggesting insulin glulisine as a possible treatment for other insulin analogmediated immunological insulin resistance [1]. We also reported a type 2 diabetic patient (patient A) who developed severe insulin resistance due to anti-insulin antibody after 2 years of use of insulin lispro and insulin detemir [2]. Switching to the treatment with insulin glulisine and insulin glargine improved glycemic control, however, anti-insulin antibody binding rate was still high. Finally, three pre-meal injections of insulin glulisine and discontinuation of insulin glargine (4 weeks) decreased anti-insulin antibody 125I-binding rate [2]. Basal insulin therapy using long-acting insulin analogs may be necessary for type 1 diabetic patient or type 2 diabetic patients who have no endogenous insulin secretion capacity. How can we treat these patients with long-acting insulin analogs-mediated anti-insulin antibody? Here, we will show the changes in HbA1c and anti-insulin antibody 125I-binding rate following the change in dose of insulin glulisine and insulin glargine in patient A (Fig. 1). Increased dose of insulin glulisine and 10 weeks-discontinuation of insulin glargine significantly decreased anti-insulin antibody 125I-binding rate, however, fasting blood glucose level (more than 200 mg/dl) and HbA1c level showed deterioration. After 10 weeks-discontinuation of insulin glargine, we re-started the use of low dose of insulin glargine. Fasting blood glucose and HbA1c levels were promptly decreased, and interestingly, anti-insulin antibody 125I-binding rate has been also continuously reduced. As the treatments for anti-insulin antibody-mediated insulin resistance or hypoglycemia, in addition to our reports [1, 2], cessation of insulin administration [3], glucocorticoids [4], the combination therapy using glucocorticoids, immunosuppressant and plasmapheresis [5, 6], and insulin lispro [7, 8] have been reported (Table 1). Increasing dose of insulin glulisine and the use of low dose of insulin glargine after the discontinuation of insulin glargine for a sufficient long period may be a new treatment for the anti-insulin antibodymediated immunological insulin resistance.

Switching to three pre-meal injections of insulin glulisine from the basal-bolus insulin therapy improves glycemic control in a patient with type 2 diabetes who had anti-insulin antibody

Switching to three pre-meal injections of insulin glulisine from the basal-bolus insulin therapy improves glycemic control in a patient with type 2 diabetes who had anti-insulin antibody

Optimal dose and timing of insulin Aspart to mimic first phase insulin response in patients with recently onset type 2 diabetes

Objective To assess the optimal dose and timing of subcutaneous injection of insulin Aspart (IAsp) in relation to meal to mimic first phase insulin response in patients with recently diagnosed type 2 diabetes. Design and methods Twenty patients were randomised in a double blind, double dummy design to four standard meal tests with pre-meal injection of insulin Aspart 0.08 IU/kg BW 30 min before the meal, insulin Aspart 0.04 IU/kg BW 30 or 15 min before the meal and placebo. Results All three insulin regimes significantly reduced postprandial glucose increment (area under the curve AUC −30 to 240 min ) and peak plasma glucose increment (Δ C max) compared with placebo. Postprandial glucose increment AUC −30 to 240 min but not Δ C max was significantly lower with IAsp 0.08 IU/kg BW as compared to IAsp 0.04 IU/kg BW, ( p < 0.03 and p = 0.18). One patient experienced hypoglycaemia after injection of IAsp 0.08 IU/kg BW. No difference in postprandial glucose profile was demonstrated whether IAsp 0.04 IU/kg BW was administrated 15 or 30 min before mealtime. Conclusions IAsp 0.04 IU/kg BW injected subcutaneously 15 or 30 min before meal reduced the postprandial blood glucose increment without risk of hypoglycaemia in patients with recently diagnosed type 2 diabetes. Doubling of the IAsp dose significantly reduced the postprandial glucose increment but increased the risk of hypoglycaemia.

Rapid-acting insulin glulisine: a new tool for postprandial glucose control

Insulin glulisine (Apidra®, Sanofi-Aventis) is a novel, rapid-acting insulin analog that replicates normal mealtime insulin secretion more closely than regular human insulin. Compared with regular human insulin, glulisine has a more rapid onset of action and shorter duration of effect, affording greater flexibility in the timing and content of meals. Additionally, optional pre- or postmeal administration makes glulisine well suited for patients who eat erratically or have difficulty remembering premeal injections. This attribute is clinically relevant because addressing postprandial hyperglycemia may help attenuate cardiovascular morbidity and mortality among diabetic patients. Insulin glulisine is safe when used for pump therapy and its rapid-acting properties are maintained consistently across patient types and body mass indices, making it an effective and versatile tool for postprandial glucose control.

Effect of pramlintide on symptom, catecholamine, and glucagon responses to hypoglycemia in healthy subjects

Pramlintide is an analog of the human glucoregulatory hormone amylin. Previous studies have shown no clear evidence that pramlintide modifies the response to insulin-induced hypoglycemia; however, a detailed assessment of responses at hypoglycemic thresholds has not been conducted. To further test the effect of pramlintide on symptom, catecholamine, and glucagon responses, a 3-step hypoglycemic clamp was investigated in healthy volunteers. In a randomized, double-blind, placebo-controlled, crossover study, 18 healthy subjects without diabetes received subcutaneous premeal injections of either placebo or 60 μg pramlintide 3 times daily for 5 consecutive days. On day 6, subjects received study drug with breakfast and, after a 7-hour fast, were connected to a Biostator for a 3-step, 3-hour clamp experiment (insulin infusion rate: 1.0 mU/kg/min; blood glucose targets: 70, 55, and 45 mg/dL). An intravenous (IV) infusion of pramlintide (16 μg/h) or placebo was initiated at t = 60 minutes. At the end of each 60-minute clamp step, autonomic (sweating, palpitations, hunger, etc) and neuroglycopenic (confusion, headache, odd behavior, etc) symptoms were assessed using a validated visual analog scale questionnaire. Blood samples were collected at 30-minute intervals for measurement of plasma glucose, insulin, pramlintide, catecholamine, and glucagon concentrations. Intraindividual and group mean responses showed that autonomic symptoms and plasma catecholamine and glucagon concentrations increased progressively during the clamp, with no discernible differences between pramlintide and placebo treatments. Group means for catecholamines at 60 minutes were: epinephrine 233 ± 42, 892 ± 85, 2,340 ± 302 and 202 ± 25, 774 ± 114, 2,751 ± 404 pg/mL and norepinephrine 1,138 ± 86, 1,236 ± 77, 1,721 ± 158 and 1,278 ± 108, 1,259 ± 109, 1,580 ±136 pg/mL (± SEM) for placebo- and pramlintide-treated groups at 70, 55, and 45 mg/dL glucose, respectively. Group means for glucagon were 72 ± 6.3, 98 ± 11.1, 130 ± 14.7 and 63 ± 3.6, 92 ± 9.4, 120 ± 16.0 pmol/L (± SEM) for placebo- and pramlintide-treated groups at 70, 55, and 45 mg/dL glucose, respectively. These results showed that pramlintide did not impair the symptom, catecholamine, and glucagon responses to insulin-induced hypoglycemia in healthy subjects.

Appetite regulation: from the gut to the hypothalamus.

these proportions had increased to 26% and 22%, respectively, with 55% of women and 66% of men being overweight (BMI > 25 kg/m 2 ; Health Survey for England, 2001), reflecting a worldwide trend which is most marked in, but not restricted to, the developed world. Most of us in affluent countries live in a privileged land of plenty where high calorie foods are easily available and in which we have a limited need for exercise. The rising prevalence of obesity in children is of particular concern (Chinn & Rona, 2001).

Premixed insulin aspart 30 vs. premixed human insulin 30/70 twice daily: a randomized trial in Type 1 and Type 2 diabetic patients

To compare the efficacy and safety of premixed insulin aspart (30% free and 70% protamine-bound, BIAsp 30) with human insulin premix (BHI 30) used in a twice-daily injection regimen in people with Type 1 and Type 2 diabetes. People with Type 1 and Type 2 diabetes (n = 294) using twice-daily insulin were randomized to a 12-week open-label comparison of BIAsp 30 and BHI 30. Efficacy was assessed by analysis of variance of 12-week data, adjusted for baseline level. BIAsp 30 was as effective as BHI 30 based on the primary efficacy measure, HbA1c, mean difference -0.01 (90% confidence interval (CI) -0.14; 0.12) %Hb. Meal-time self-measured blood glucose increment averaged over the three main meals was significantly lower in the BIAsp 30 group than in the BHI 30 group (-0.68 (-1.20; -0.16) mmol/l; P < 0.02). Significant improvements were observed after breakfast, before lunch, after dinner and at bedtime (P < 0.02-0.05), with blood glucose around 1.0 mmol/l lower in the BIAsp 30 group. The number of major hypoglycaemic episodes with BIAsp 30 was half that with BHI 30. However, the overall risk of both minor and major hypoglycaemia did not differ significantly between treatments. Post-prandial glycaemic control was significantly improved, without increasing the risk of hypoglycaemia, and overall control was similar when people with Type 1 and Type 2 diabetes were treated on a twice-daily regimen with immediate premeal injections of BIAsp 30 compared with BHI 30.

Twice-daily biphasic insulin aspart 30 versus biphasic human insulin 30: A double-blind crossover study in adults with type 2 diabetes mellitus

Objective: The purpose of this study was to compare the pharmacokinetics and pharmacodynamics of the premixed insulin analogue biphasic insulin aspart (BIAsp 30) with the equivalent premixed biphasic human insulin (BHI 30), administered twice daily, in patients with type 2 diabetes mellitus. Methods: In this randomized, double-blind, crossover trial, 13 patients (mean age, 64 years; baseline mean glycosylated hemoglobin, 7.7%; mean body mass index, 28.1 kg/m 2) received 2 weeks of treatment with BIAsp 30 and 2 weeks of BHI 30 administered immediately before dinner and breakfast. At the end of each 2-week treatment period, 24-hour serum insulin and glucose profiles were determined using specific 2-sided enzymelinked immunosorbent assays. All pharmacodynamic and pharmacokinetic end points were analyzed using analysis of variance. Results: Total daily insulin exposure was similar between treatment periods. Mean area under the total insulin concentration-time profile during the 2 hours following administration of BIAsp 30 was 17% greater than that of BHI 30 after dinner and 44% greater after breakfast; both differences were statistically significant. The maximum serum insulin aspart concentrations following BIAsp 30 were significantly higher after dinner (18%) and breakfast (35%). Peak serum insulin concentration was reached 1 hour earlier after breakfast and 45 minutes earlier after dinner in the BIAsp 30 group; differences were significant only after breakfast. The mean daily prandial glucose excursion was significantly lower for BIAsp 30 (16.2 mmol·h·L −1) than BHI 30 (17.9 mmol·h·L −1). Postprandial 4-hour glucose excursions were significantly lower with BIAsp 30 than with BHI 30 after dinner and breakfast, but were significantly greater after lunch. Mean 24-hour and nocturnal serum glucose concentrations were similar, and both insulins were associated with ≤7 minor and no major hypoglycemic events. Conclusions: Premeal injection of BIAsp 30 in a twice-daily regimen significantly reduced overall postprandial glucose excursions. This effect may be of importance when improvement in postprandial glucose control is desired.

Recent advances in treatment of youth with Type 1 diabetes: better care through technology.

While treatment of Type 1 diabetes mellitus (T1DM) in children and adolescents is especially difficult, recent technological advances have provided new therapeutic options to clinicians and patients. The urgency to achieve strict diabetes control and the introduction of new and improved insulin pumps have been accompanied by a marked increase in use of continuous subcutaneous insulin infusion (CSII) therapy in youth with diabetes. Results of clinical outcome studies indicate that CSII provides a safe and effective alternative to multiple daily injection (MDI) therapy, even when employed in a regular clinic setting in a large number of children. The safety and efficacy of CSII is further enhanced by the introduction of lispro and aspart insulin. The sharper peaks and shorter duration of action of these very rapid-acting insulin analogues provides a means to achieve better control of post-prandial hyperglycaemia with less late post-prandial and nocturnal hypoglycaemia. Glargine insulin, a soluble and essentially peakless long-acting insulin analogue, may provide a better basal insulin for MDI regimens, but there are limited published data with this agent in children with T1DM. A number of systems for pulmonary delivery of insulin are in development and preliminary results of Phase III studies have been promising. Like CSII, inhaled insulin allows the child to take bolus insulin doses before each meal without having to take a premeal injection. A major obstacle to effective treatment is that self-monitoring of three to four blood glucose levels a day often misses the marked glycaemic excursions that characterize T1DM in young patients. On the other hand, new continuous glucose sensing systems provide a wealth of data that can be used to optimize basal and bolus therapy, regardless of how insulin is administered. Even more important, we may finally be at the threshold of development of a practically applicable artificial pancreas.

Improved postprandial glycemic control with humalog ® mix75/25 ™ after a standard test meal in patients with type 2 diabetes mellitus

Objective This double-blind study was designed to compare the postprandial glucodynamic profile of Humalog ® Mix75/25 ™, a new premixed insulin analogue containing 75% neutral protamine lispro and 25% insulin lispro with that of human insulin 70/30 (70% neutral protamine Hagedorn insulin and 30% regular human insulin) in patients with type 2 diabetes mellitus. Background Insulin lispro Mix75/25 (Mix75/25) is the first available insulin formulation in which both the rapid-acting and basal components are insulin analogues. Methods This randomized, multicenter, double-blind, crossover study monitored patients' postprandial glucodynamic response to Mix75/25 and human insulin 70/30 (70/30) after a standard test meal. Eighty-four patients with type 2 diabetes participated in this study and were randomly assigned to 1 of 2 treatment sequence groups. Patients received an identical test meal on 4 occasions, completing 2 test meals for each treatment. Equal doses of Mix75/25 or 70/30 were administered 5 minutes before each of the 2 test meals, with doses individualized for each patient. Blood samples were collected for 4 hours after the meal for measurement of plasma glucose. From these plasma glucose measurements, fasting plasma glucose, 2-hour postprandial glucose (2pp), 2-hour postprandial glucose excursion (2pp ex), maximum glucose excursion (Gex max), the area under the glucose concentration versus time curve from 0 to 4 hours (AUC 4), and the area under the glucose excursion versus time curve from 0 to 4 hours (AUCex 4) were calculated. Results Because of significant differences in the baseline fasting plasma glucose levels between Mix75/25 and 70/30 (Mix75/25: 8.9 ± 2.2 mmol/L [160.2 ± 39.6 mg/dL]; 70/30: 8.6 ± 1.9 mmol/L [154 ± 34 mg/dL), analyses of the excursion parameters provide a truer comparison of the glucodynamic response between insulin formulations. Mix75/25 resulted in significantly lower values for 2pp ex (3.35 ± 2.28 vs 4.13 ± 2.26 mmol/L), Gex max (4.51 ± 1.88 vs 5.19 ± 1.98 mmol/L), and AUCex 4 (8.01 ± 7.02 vs 10.6 ± 6.47 mmol·h/L) compared with 70/30. Conclusions In patients with type 2 diabetes mellitus, premeal injection of Mix75/25 resulted in better postprandial glycemic control than did premeal injection of 70/30 in the 4 hours after a standard meal. Mix75/25 is a valuable option for managing postprandial blood glucose in patients with type 2 diabetes mellitus who require insulin.

Unchanged Insulin Absorption After 4 Days' Use of Subcutaneous Indwelling Catheters for Insulin Injections

Since 1985, we have used indwelling catheters (Insuflon, Maersk Medical, Lynge, Denmark; Chronimed, Minnetonka, MN) to lessen pain when injecting insulin. However, some patients experience a rise in blood glucose after using indwelling catheters for a few days. We therefore studied the absorption of 125I-labeled insulin when using indwelling catheters. Five men and five women participated (age 18-25 years, C-peptide negative, HbA1c 9.0 +/- 1.0% [mean +/- SD, DCA-2000 method], diabetes duration 5-21 [median 9.5] years). After thyroid blockage with potassium iodide, we injected 5IU of 125I-labeled short-acting insulin subcutaneously in the abdomen ("ordinary injection") and 5 IU on the contralateral side through an indwelling catheter ("catheter injection"). The injection/insertion area was free of lipohyper- and lipohypotrophies. Disappearance rate was measured for 180 min with a gamma camera. The patients injected all premeal injections of short-acting insulin through the same indwelling catheter in the following 4 days. The investigation procedure was repeated day 3 and 5. We found no statistically or clinically (95% CI) significant difference in residual activity of 125I-insulin after 60 min or in time for 50% of the injected depot to disappear (T-50%) among catheter injections on day 1, 3, and 5; ordinary injections on days 1, 3, and 5; or catheter and ordinary injections on days 1, 3, and 5, respectively. HbA1c correlated both to T-50% (r = 0.73, P = 0.016) and residual activity of 125I-insulin after 60 min (r = 0.69, P = 0.028), indicating that patients with a slower absorption will have a less ideal metabolic control when using premeal bolus injections. We conclude that using indwelling subcutaneous catheters for insulin injections for up to 4 days does not affect the absorption of short-acting insulin.

Double‐blind Crossover Study of Acarbose in Type 1 Diabetic Patients

The addition of acarbose to insulin treatment was evaluated in 14 Type 1 (insulin-dependent) diabetic patients assessed conventionally (blood glucose profile and HbA1c measurement) and with an artificial B-cell. Their metabolic control was poor, fasting blood glucose 10.7 +/- 0.3 (+/- SE) mmol l-1, mean daily blood glucose 9.7 +/- 0.3 mmol l-1, and HbA1c 9.6 +/- 0.2% (normal range 5.0-6.1%). They were of normal body weight (body mass index 22.5 +/- 0.3 kg m-2), and were C-peptide deficient (fasting 0.08 +/- 0.02 nmol l-1). In addition to their usual insulin therapy (46.9 +/- 3.5 U day-1 in three pre-meal injections), they received 100 mg acarbose or placebo three times a day for 6 weeks in a randomized double-blind crossover design. On the last day of either acarbose or placebo treatment, the usual insulin therapy was discontinued and an artificial B-cell was used for insulin delivery, programmed for euglycaemia. Placebo or acarbose was continued before meals. Acarbose reduced mean daily blood glucose concentrations (8.5 +/- 0.3 vs 9.7 +/- 0.3 mmol l-1, p = 0.002) and HbA1c levels (8.3 +/- 0.1 vs 9.6 +/- 0.2%, p less than 0.001). A significant reduction in insulin requirement after meals was found with the artificial B-cell, 25.1 +/- 2.5 (first treatment acarbose) and 24.1 +/- 2.9 U (first treatment placebo) with acarbose and 40.0 +/- 2.5 and 35.6 +/- 2.9 U with placebo (p less than 0.001). These results suggest that acarbose could usefully be administered to Type 1 diabetic patients to ameliorate glucose control and reduce insulin requirement.

The influence of different insulin regimens on quality of life and metabolic control in insulin-dependent diabetics

Administration of insulin with premeal boluses of short-acting insulin using a new injection device (Novopen) was compared with a conventional three times daily injection regimen regarding aspects of quality of life and metabolic control in insulin-dependent diabetes mellitus (IDDM). Eighteen C-peptide-negative patients with IDDM (16 men, two women, aged 31.0 ± 7.4 years, duration of diabetes 13.0 ± 4.6 years; mean ± SD) participated in the study. All patients had been treated with three daily insulin injections for at least 1 year prior to the study. The patients were randomized into two groups. Group A started a 3-month treatment period with premeal injections of short-acting insulin and intermediate-acting insulin at bedtime. This period was followed by another 3 months using the initial three times daily injection regimen. Group B completed the study in the reverse order. Quality of life was assessed by using questionaires and personal interviews by the same clinical psychologist. Metabolic control was assessed by measuring the levels of glycosylated hemoglobin. The results show that both treatment groups experienced a general improvement in mood and well-being during the period with multiple insulin injection treatment. Furthermore, during the periods of insulin pen treatment, an increased experience of freedom and less dependence on fixed meal times were noted. Overall metabolic control, insulin dosage, body weight, and number of hypoglycemic episodes did not changes during the study. It is concluded that metabolic control, safety, and number of hypoglycemic episodes using premeal doses of short-acting insulin using Novopen were not different from those seen during conventional treatment. However, the experienced effects and consequences on quality of life during this treatment regimen were generally more positive with an increased feeling of freedom and improvement in mood.