Biomedical subjects

Sherwyn Schwartz

Publications and source records attributed to Sherwyn Schwartz.

15 recordsLinked to original sources

PubMed2006

A single-center, randomized, double-blind, three-way crossover study examining postchallenge glucose responses to human insulin 70/30 and insulin lispro fixed mixtures 75/25 and 50/50 in patients with type 2 diabetes mellitus.

OBJECTIVE: The aim of this study was to test the ability of human insulin 70/30, insulin lispro mixture 75/25 (75% neutral protamine lispro [NPL], 25% insulin lispro), and insulin lispro mixture 50/50 (50% NPL, 50% insulin lispro) to control postprandial glucose (PPG) concentrations in patients with type 2 diabetes mellitus (DM). METHODS: This single-center, randomized, double-blind, 3-way crossover study was conducted at the Diabetes and Glandular Disease Research Center, San Antonio, Texas. We measured serum glucose responses after a standardized breakfast test meal (500 kcal; 50% carbohydrate, 34% fat, 16% protein) in patients with type 2 DM receiving a single preprandial dose of human insulin 70/30, insulin lispro 75/25, or insulin lispro 50/50 by SC injection. All patients previously used insulin for at least 1 month prior to the study. The glucose responses were compared with those of healthy, untreated subjects administered the identical meal. RESULTS: A total of 33 patients were enrolled (23 with type 2 DM and 10 healthy controls). The baseline characteristics of the patients were as follows: sex ratio (M:F), 17:6; mean (SD) age, 61.3 (10.0) years; mean (SD) body weight, 98.5 (13.2) kg; mean (SD) body mass index, 33.0 (3.8) kg/m(2); mean (SD) glycosylated hemoglobin, 8.1% (1.6%); mean (SD) fasting serum glucose (FSG), 158.7 (27.6) mg/dL; and 56.5% white, 8.7% black, and 34.8% Hispanic. The mean (SD) doses (U/d) of the fixed-mixture preparations were similar: human insulin 70/30, 44.1 (18.2); insulin lispro 75/25, 44.1 (18.2); and insulin lispro 50/50, 43.8 (17.8). FSG levels obtained before the test meal were not significantly different between treatments. Compared with those in healthy subjects, incremental glucose AUC values for the 4 hours after the meal (AUCglucose 0-4) for patients with type 2 DM were 6.4-fold higher with human insulin 70/30, 4.6-fold higher with insulin lispro 75/25, and 3.0-fold higher with insulin lispro 50/50. Each insulin regimen produced AUC(glucose) 0-4 and 2-hour PPG values significantly different from all other regimens (all, P < 0.05). Mean (SD) 2-hour PPG values (mg/dL) were lower with mixtures containing insulin lispro than with human insulin 70/30 and decreased as the proportion of insulin lispro within the fixed mixtures increased: human insulin 70/30, 212.6 (47.0); insulin lispro 75/25, 198.0 (67.5); and insulin lispro 50/50, 158.8 (52.3). CONCLUSIONS: In this small study in patients with type 2 DM and healthy controls, preprandial administration of a fixed mixture containing rapid-acting or regular insulin and intermediate-acting components was associated with attenuation of the rise in PPG in patients with type 2 DM administered a test meal. Mixtures containing insulin lispro were associated with greater decreases in PPG concentrations compared with human insulin 70/30. Furthermore, greater amounts of rapid-acting insulin contained within the mixture were associated with better PPG control.

Aged↗

PubMed2006

Is there a rationale for insulin therapy in pre-diabetic individuals?

Type 2 diabetes mellitus is usually preceded by impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG), which are often referred to as pre-diabetes. Individuals with IGT demonstrate beta-cell dysfunction, insulin resistance, and increased hepatic glucose production; IGT and IFG are risk factors for both diabetes and cardiovascular disease. Type 2 diabetes is associated with micro- and macrovascular complications that lead to excessive mortality and morbidity and the risk of microvascular complications extends to people with pre-diabetes. Maintaining good glycemic control in type 2 diabetes can reduce the risk of developing chronic disease-associated complications. Most individuals who develop type 2 diabetes appear to pass through a stage of IFG or IGT; thus, early intervention (lifestyle and/or pharmacologic) in individuals with pre-diabetes may help prevent cardiovascular disease and the development of type 2 diabetes.The use of exogenous insulin treatment offers the potential to reduce the cardiovascular risk in individuals with type 2 diabetes or pre-diabetes through effective reductions in blood glucose and lipid levels, and in the associated tissue damage resulting from their chronic elevations. However, there are barriers associated with insulin initiation in both type 2 diabetes and pre-diabetes (e.g. hypoglycemia, weight gain, the possible unpredictable action of long-acting insulin, and the need for injections). Insulin glargine, with its flat time-action profile, near 24-hour duration of action, reduced risk of hypoglycemia, and improved glycemic control compared with insulin suspension isophane (neutral protamine hagedorn [NPH] insulin), may help to overcome some of these barriers.Initial results from a small study have indicated the feasibility of treating individuals with pre-diabetes to near-normoglycemia using a regimen of low-dose insulin glargine plus caloric restriction. This is being followed up in the ongoing ORIGIN (Outcomes Reduction with Initial Glargine INtervention) study, which will investigate whether treatment to near-normoglycemia with insulin glargine in individuals with IGT, IFG, or new-onset type 2 diabetes can reduce cardiovascular morbidity and mortality compared with conventional management of these conditions, and whether the rate of progression to type 2 diabetes can be similarly reduced.Further studies are needed to investigate the potential benefits of insulin therapy in individuals with pre-diabetes.

Cardiovascular Diseases↗

PubMed2006

Improvement in glycemic excursions with a transcutaneous, real-time continuous glucose sensor: a randomized controlled trial.

OBJECTIVE: Hypoglycemia and wide glucose excursions continue to be major obstacles to achieving target HbA(1c) values and the associated reductions in long-term complications (and economic costs) in people with insulin-treated diabetes. In this study we evaluated the accuracy, safety, and clinical effectiveness of a continuous glucose-sensing device. RESEARCH DESIGN AND METHODS: A total of 91 insulin-requiring patients with type 1 (n = 75) and type 2 (n = 16) diabetes were enrolled in this multicenter randomized study. Subjects wore a transcutaneous, 3-day, continuous glucose-sensing system for three consecutive 72-h periods. Subjects were randomly assigned (1:1 ratio) to either a control group (continuous glucose data not provided) or a display group (continuous glucose data not provided during period 1 but displayed during periods 2 and 3). During periods 2 and 3, patients in the display group had real-time access to sensor glucose values, could review glucose trends over the preceding 1, 3, and 9 h, and were provided with high (> or = 200 mg/dl) and low (< or = 80 mg/dl) alerts and a low (< or = 55 mg/dl) alarm. Sensors were inserted by patients, and both groups used (or wore) the system during daily activities. Device accuracy was assessed by comparing continuous glucose values to paired self-monitoring of blood glucose (SMBG) meter readings. Clinical effectiveness was evaluated by analyzing between-group (control vs. display, periods 2 and 3) and within-group (display, period 1 vs. period 3) differences in time spent in high, low, and target (81-140 mg/dl) glucose zones. RESULTS: When prospective, real-time sensor values were compared with SMBG values, 95.4% of 6,767 paired glucose values fell within Clarke error grid A and B zones. Pearson's correlation coefficient was 0.88, and mean and median absolute relative differences were 21.2 and 15.9%, respectively. No systematic bias was detected at any of the prespecified glucose levels (50, 80, 100, 150, and 200 mg/dl). When compared with control subjects, the display group spent 21% less time as hypoglycemic (<55 mg/dl), 23% less time as hyperglycemic (> or = 240 mg/dl), and 26% more time in the target (81-140 mg/dl) glucose range (P < 0.001 for each comparison). Nocturnal (10:00 p.m. to 6:00 a.m.) hypoglycemia, as assessed at two thresholds, was also reduced by 38% (<55 mg/dl; P < 0.001) and 33% (55-80 mg/dl; P < 0.001) in the display group compared with control subjects. CONCLUSIONS: We conclude that real-time continuous glucose monitoring for periods up to 72 h is accurate and safe in insulin-requiring subjects with type 1 and type 2 diabetes. This study demonstrates that availability of real-time, continuously measured glucose levels can significantly improve glycemic excursions by reducing exposure to hyperglycemia without increasing the risk of hypoglycemia, which may reduce long-term diabetes complications and their associated economic costs.

Adult↗

PubMed2006

Efficacy, tolerability, and safety of a novel once-daily extended-release metformin in patients with type 2 diabetes.

OBJECTIVE: The purpose of this study was to determine the efficacy and safety of a novel extended-release metformin in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Adults with type 2 diabetes (newly diagnosed, treated with diet and exercise only, or previously treated with oral diabetic medications) were randomly assigned to receive one of three extended-release metformin treatment regimens (1,500 mg/day q.d., 1,500 mg/day twice daily, or 2,000 mg/day q.d.) or immediate-release metformin (1,500 mg/day twice daily) in a double-blind 24-week trial. RESULTS: Significant decreases (P < 0.001) in mean HbA(1c) (A1C) levels were observed by week 12 in all treatment groups. The mean changes from baseline to end point in the two groups given 1,500 mg extended-release metformin (-0.73 and -0.74%) were not significantly different from the change in the immediate-release metformin group (-0.70%), whereas the 2,000-mg extended-release metformin group showed a greater decrease in A1C levels (-1.06%; mean difference [2,000 mg extended-release metformin - immediate-release metformin]: -0.36 [98.4% CI -0.65 to -0.06]). Rapid decreases in fasting plasma glucose levels were observed by week 1, which continued until week 8, and were maintained for the duration of the study. The overall incidence of adverse events was similar for all treatment groups, but fewer patients in the extended-release metformin groups discontinued treatment due to nausea during the initial dosing period than in the immediate-release metformin group. CONCLUSIONS: Once- or twice-daily extended-release metformin was as safe and effective as twice-daily immediate-release metformin and provided continued glycemic control for up to 24 weeks of treatment.

Adolescent↗

PubMed2005

Glycemic characteristics in continuously monitored patients with type 1 and type 2 diabetes: normative values.

OBJECTIVE: The purpose of this study was to generate normative values for periods of euglycemia as well as for daily patterns of glycemic excursions in patients with type 1 and type 2 diabetes monitored continuously for a maximum period of 21 days and blinded to glucose levels. RESEARCH DESIGN AND METHODS: This was a multicenter, prospective observational study in which 101 consecutive patients with type 1 (n = 60) or type 2 (n = 41) diabetes underwent blinded continuous glucose monitoring. Serial glucose measurements were divided into periods of euglycemia (70-180 mg/dl), hyperglycemia (>180 mg/dl), and hypoglycemia (<70 mg/dl). The proportions of time patients were hypoglycemic, euglycemic, and hyperglycemic and the total areas under the curves (AUCs) were determined. RESULTS: During the observation period the 101 subjects contributed an average 287 +/- 132 h of continuous glucose values. Subjects remained in the euglycemic range for approximately 63% of the total day, were hypoglycemic 8%, and were hyperglycemic 29%. Hypoglycemia was more prevalent nocturnally (11 vs. 7%) and hyperglycemia diurnally (31 vs. 25%). Compared with subjects with type 2 diabetes, type 1 diabetic subjects had more frequent hypoglycemic episodes per day (2.1 vs. 1.0; P < 0.001) that were of longer duration (1.1 vs. 0.7 h; P < 0.0001), reflecting a greater number of hours per day in the hypoglycemic range (2.3 vs. 1.0 h; P < 0.0001). The mean hypoglycemic AUC values were >150% higher for type 1 compared with type 2 diabetic subjects (41 vs. 16, respectively; P < 0.0001). CONCLUSIONS: These normative data will assist in study and sample size planning for future investigations of continuous glucose monitoring and allow for qualitative comparisons with trials of therapeutic interventions aimed at reducing the occurrence of glycemic excursions.

Adult↗

PubMed2004

A multicenter, open-label, randomized, two-period crossover trial comparing glycemic control, satisfaction, and preference achieved with a 31 gauge x 6 mm needle versus a 29 gauge x 12.7 mm needle in obese patients with diabetes mellitus.

BACKGROUND: Optimal needle length for subcutaneous insulin injection may differ for obese and nonobese patients, which could affect management of diabetes mellitus (DM). OBJECTIVE: The aim of this study was to determine whether 31 gauge (G) x 6 mm (shorter) needles are appropriate alternatives to 29 G x 12.7 mm (longer) needles in obese patients with DM. METHODS: A multicenter, open-label, randomized, 2-period crossover trial was conducted in insulin-treated patients with type 1 or 2 DM with body mass index >or=30 kg/m(2) and glycosylated hemoglobin A(1c) (HbA(1c)) concentration <or=10%. All patients used the same injection device and were randomized to receive 12 weeks of therapy with 1 injection site (thigh or abdomen) and 1 of the 2 needle lengths. Patients used the same injection site but the alternate needle during the second 12-week period. RESULTS: Sixty-two patients (31 men, 31 women; mean [SD] age, 50.5 [10.6] years; age range, 20-73 years) received treatment. Fifty-six patients completed all 24 weeks of treatment. No differences in glycemic control were found. Double-blind assessments of pain scores and leakage measurements, and results from the World Health Organization Diabetes Treatment Satisfaction Questionnaire and most sections of the Insulin Treatment Satisfaction Questionnaire (ITSQ), indicated no differences. However, patients indicated greater satisfaction with the shorter needle on the ITSQ (P < 0.001). The most common adverse event was injection-site bruising (51% [30/59] for the longer needle vs 34% [21/61] for the shorter needle; P = NS). Eighty-nine percent of patients (49/55) preferred the shorter needle (P < 0.001), and 76% (42/55) had a strong, very strong, or extremely strong preference for it. CONCLUSIONS: In obese patients, use of 31 G x 6 mm and 29 G x 12.7 mm needles produced comparable HbA(1c) values, double-blind pain and leakage scores, convenience, and ease of use. However, patients preferred the shorter needle.

Adult↗

PubMed2004

Preference and resource utilization in elderly patients: InnoLet versus vial/syringe.

InnoLet is a disposable insulin injection device with a large easy-to-read dial, large push button for injection, and audible clicks for each unit injected. This clinical trial assessed patient preference, satisfaction, and utilization of healthcare resources (estimated nursing care) for InnoLet and vial/syringe. Patients with diabetes mellitus (N=79, mean age 68.2+/-8.6 years, duration of diabetes 16.5+/-10.9 years) having visual and/or motor disabilities and having difficulty (or required caregiver assistance) for previous injections by vial/syringe were randomized to use of either InnoLet or vial/syringe for 6 weeks, then switched to the alternate regimen for 6 weeks. At the end of the study, utilization of healthcare resources was assessed in terms of the caregiver time required to assist in preparation, storage, and disposal of each device. For vial/syringe, 60% of patients required assistance in drawing up the appropriate dosage in the syringe, and 36% of patients required assistance when injecting insulin. A major portion of the patients (53%) could independently conduct injections (without nursing/caregiver assistance) during use of InnoLet, versus 20% for vial/syringe. As a result, mean daily nursing costs associated with the injection regimen were US$ 114 for the InnoLet device, and US$ 196 for vial/syringe (P<0.001). A majority of patients (82%) indicated a preference for the InnoLet device (P<0.001).

Aged↗

PubMed2004

Alarms based on real-time sensor glucose values alert patients to hypo- and hyperglycemia: the guardian continuous monitoring system.

The purposes of this study were to demonstrate the accuracy and effectiveness of the Guardian Continuous Monitoring System (Medtronic MiniMed, Northridge, California) and to demonstrate that the application of real-time alarms to continuous monitoring alerts users to hypo and hyperglycemia and reduces excursions in people with diabetes. A total of 71 subjects with type 1 diabetes, mean hemoglobin A1c of 7.6 +/- 1.1%, age 44.0 +/- 11.4 years, and duration of diabetes 23.6 +/- 10.6 years were enrolled in this two-period, randomized, multicenter study. Subjects were randomized into either an Alert group or a Control group. The accuracy of the Guardian was evaluated by treating the study data as a single-sample correlational design. Effectiveness of the Guardian alerts was evaluated by comparing the Alert group with the Control group. The mean (median) absolute relative error between home blood glucose meter readings and sensor values was 21.3% (17.3%), and the Guardian, on average, read 12.8 mg/dL below the concurrent home blood glucose meter readings. The hypoglycemia alert was able to distinguished glucose values < or =70 mg/dL with 67% sensitivity, 90% specificity, and 47% false alerts. The hyperglycemia alert showed a similar ability to detect sensor values > or =250 mg/dL with 63% sensitivity, 97% specificity, and 19% false alerts. The Alert group demonstrated a median decrease in the duration of hypoglycemic excursions (-27.8 min) that was significantly greater than the median decrease in the duration of hypoglycemic excursions in the Control group (-4.5 min) (P = 0.03). A marginally significant increase in the frequency of hyperglycemic excursions (P = 0.07) between Period 1 and Period 2 was accompanied by a decrease of 9.6 min in the duration of hyperglycemic excursions in the Alert group. Glucose measurements differ between blood samples taken from the finger and interstitial fluid, especially when levels are changing rapidly; however, these results demonstrate that the Guardian is reasonably accurate while performing continuous glucose monitoring. The subjects' responses to hypoglycemia alerts resulted in a significant reduction in the duration of hypoglycemic excursions; however, overtreating hypoglycemia may have resulted in a marginally significant increase in the frequency of hyperglycemic excursions.

Adult↗

PubMed2004

The impact of insulin glargine on clinical and humanistic outcomes in patients uncontrolled on other insulin and oral agents: an office-based naturalistic study.

OBJECTIVE: Controlling blood glucose levels in patients with diabetes often requires aggressive treatment, which may in turn cause hypoglycemia and/or decreased health-related quality of life (HRQOL). Insulin glargine, a long-acting insulin, has shown benefits of decreased nocturnal hypoglycemia without significant weight gain, while providing good glycemic control in clinical trials. These benefits have often been reported in studies of less than 1 year duration. The objective of this study was to evaluate the effectiveness of insulin glargine over a 12-month period in a clinical practice setting, and measure its effects on HRQOL in a subset of patients. DESIGN AND METHODS: Patients with diabetes in a large private endocrinology practice were initiated on insulin glargine. Patients were divided into 2 cohorts: the first group included patients with type 1 diabetes (T1D, n = 135); the second group included patients with type 2 diabetes previously on insulin and/or oral agents (T2D, n = 180). The HRQOL subset analysis included 50 patients from the above study. Patients completed a 40-item questionnaire adapted from the Diabetes Symptom Checklist-Revised (DSC-R) and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) at weeks 0, 2, 6, 12, and 16. RESULTS: Patients in both cohorts experienced statistically significant decreases in mean ( +/- SD) A1C: group T1D, -0.28 +/- 1.47 (P = 0.0307); group T2D, -0.60 +/- 1.51 (P < 0.0001), with no significant changes in body mass index. In the year following insulin glargine therapy, there were significantly fewer hypoglycemic events per patient than in the year prior to insulin glargine therapy (group T1D: -0.33, P = 0.002; group T2D: -0.20, P = 0.004). HRQOL subset analysis also revealed a significant decrease in A1C (P < 0.0001) after 16 weeks of therapy with insulin glargine. In this subset of patients, there was a significant improvement in overall well being (P = 0.0019), emotional well being (P = 0.003), total symptom scores (P < 0.0001), and total symptom distress (P < 0.0001). The limitations of the study are those inherently associated with naturalistic observational studies such as recall bias and compliance. CONCLUSIONS: Insulin glargine use over a 12-month period in a clinical practice setting was shown to significantly improve A1C without adversely impacting weight or the occurrence of hypoglycemia. Significant improvements were also observed in HRQOL.

Administration, Oral↗

PubMed2004

Oral insulin therapy to prevent progression of immune-mediated (type 1) diabetes.

Repeated ingestion of insulin has been suggested as an immune tolerization therapy to prevent immune-mediated (type 1) diabetes. We performed a placebo-controlled, two-dose, oral insulin tolerance trial in newly diagnosed (< 2 years) diabetic patients who had required insulin replacement for less than 4 weeks and were found to have cytoplasmic islet cell autoantibodies (ICAs). No oral hypoglycemic agents were permitted during the trial. Endogenous insulin reserves were estimated at six-month intervals by plasma C-peptide responses to a mixed meal. Positive ICAs were found in 262 (31%) of the 846 patients screened. Of the 197 who agreed to participate, 187 could be followed for 6 to 36 months. Endogenous insulin retention was dependent upon initial stimulated C-peptide response, age at diabetes onset, and numbers of specific islet cell autoantibodies found. Oral insulin improved plasma C-peptide responses in patients diagnosed at ages greater than 20 years, best seen at the low (1 mg/day) over the high (10 mg/day) insulin dose (P = .003 and P = .01, respectively). In patients diagnosed before age 20 years, the 1 mg dose was ineffective, whereas the 10 mg dose actually accelerated C-peptide loss (P = .003). There were no adverse effects. If confirmed, these findings suggest that diabetic patients over age 20 years with ICA evidence of late-onset immune-mediated diabetes should be considered for oral insulin at 1 mg/day to better retain endogenous insulin secretion.

Administration, Oral↗

PubMed2004

Improved glucose excursions using an implantable real-time continuous glucose sensor in adults with type 1 diabetes.

OBJECTIVE: The capability of emerging glucose sensor technology to continuously monitor glucose levels may provide ways to achieve glycemic targets while reducing hypoglycemia. RESEARCH DESIGN AND METHODS: A first-generation, long-term continuous glucose sensor (DexCom, San Diego, CA) was implanted subcutaneously in 15 patients with type 1 diabetes. Safety, efficacy, and potential benefits were evaluated during a blinded control period and in a study period during which patients had real-time access to the glucose data. RESULTS: The bias differences between self-monitored blood glucose (SMBG) and sensor data were <15% at 2.8, 4.4, 5.6, 8.3, and 11.1 mmol/l. No procedure or device-related adverse events were observed. Of 15 patients, 13 (87%) had functional sensors during the 12-h simulated home use study with 96% of points in the A and B regions of the Clarke error grid, an R value of 0.88, and a mean absolute relative difference of 16% when retrospectively compared with SMBG. In actual home use, during the blinded control period (50 +/- 16 days) data were not displayed to the patient, whereas during the unblinded study period (44 +/- 17 days) the data were presented to the patient, and alerts were set at 3.1, 5.6, and 11.1 mmol/l. Patients spent a median of 47% less time below 3.1 mmol/l (P<0.05) and 25% less time above 13.3 mmol/l (P<0.05) during the nonblinded study period compared with the blinded control period. CONCLUSIONS: The availability of real-time continuous glucose values may help patients reduce their hyperglycemic excursions and lower the risk of hypoglycemia.

Adult↗

PubMed2003

A continuous glucose sensor based on wired enzyme technology -- results from a 3-day trial in patients with type 1 diabetes.

Wired Enzyme (Therasense, Alameda, CA) sensing technology for continuous measurement of in vivo glucose concentrations offers the benefits of (1). excellent sensor stability, (2). reduced susceptibility to variations of in vivo oxygen concentration, and (3). minimized response to common electroactive interferents. This study describes the response of 48 sensors (25 in the upper arm, 23 in the abdomen) implanted for 3 days in patients with Type 1 diabetes. Prospective calibration was performed using capillary blood; results were compared with venous plasma glucose values obtained at 15-min intervals. Ninety-eight percent of readings fell in the clinically accurate Clarke error grid zone A or clinically acceptable zone B. Choice of the site of the implanted sensor (upper arm vs. abdomen) or the capillary blood calibration site (arm vs. finger) did not affect system accuracy.

Abdomen↗

PubMed2003

Pramlintide reduces postprandial glucose excursions when added to regular insulin or insulin lispro in subjects with type 1 diabetes: a dose-timing study.

OBJECTIVE: To assess the postprandial glucose-lowering effect of the human amylin analog pramlintide when given with either regular insulin or insulin lispro in subjects with type 1 diabetes, with an emphasis on the optimal dose timing relative to meals. RESEARCH DESIGN AND METHODS: In this randomized, single-blind, placebo-controlled, five-way crossover study, 19 subjects with type 1 diabetes using regular insulin and 21 subjects with type 1 diabetes using insulin lispro underwent five consecutive mixed meal tests. In randomized order, subjects received subcutaneous injections of placebo at -15 min or 60 microg pramlintide at -15, 0, +15, or +30 min relative to the meal after an overnight fast. Regular insulin or insulin lispro was injected at -30 and 0 min, respectively, at doses that were adjusted appropriately for both the content of the standardized meal and the anticipated effects of pramlintide. Plasma glucose concentrations were measured before and during the 4-h postmeal period. RESULTS: In both the regular insulin and insulin lispro groups, pramlintide injections at all four time points lowered the postprandial glucose excursion (36 to >100% reduction in incremental area under the concentration time curve from 0 to 4 h (AUC(0-4 h)) compared with placebo. However, only preprandial injections of pramlintide (-15 and 0 min) were able to prevent the initial postprandial surge in glucose. The optimal time for pramlintide injection was 0 min, which reduced the postprandial glucose excursion by >100% compared with regular insulin plus placebo (incremental AUC(0-4 h): -0.6 +/- 2.5 vs. 11.0 +/- 2.9 mmolx h(-1) x l(-1), P < 0.0007) and by 75% compared with insulin lispro plus placebo (incremental AUC(0-4 h): 2.5 +/- 2.1 vs. 10.0 +/- 2.5 mmol x h(-1) x l(-1), P < 0.0098). No serious adverse events were reported. CONCLUSIONS: Pramlintide, given at or just before a meal, reduces the postprandial glucose excursion in subjects with type 1 diabetes, regardless of whether added to regular insulin or a rapid-acting insulin analog.

Adolescent↗

PubMed2003

Insulin 70/30 mix plus metformin versus triple oral therapy in the treatment of type 2 diabetes after failure of two oral drugs: efficacy, safety, and cost analysis.

OBJECTIVE: Subjects (n = 188) with type 2 diabetes and inadequate response to two oral medications (A1C >8.0%) were randomly assigned to treatment with either a third oral medication or an insulin 70/30 mix b.i.d. plus metformin for a comparison of efficacy, safety, and cost. RESEARCH DESIGN AND METHODS: The protocol called for aggressive dose titration to achieve target values of fasting blood glucose (80-120 mg/dl), postprandial glucose (<160 mg/dl), and A1C (<7%). These efficacy parameters were evaluated at weeks 2, 6, 12, and 24 of therapy. If dose adjustments failed to achieve targeted glycemic control, subjects were switched to an alternate therapy. RESULTS: At the end of study (week 24 of therapy), A1C and fasting plasma glucose (FPG) values showed comparable decreases in the two treatment groups. Only 31% (oral therapy) and 32% (insulin plus metformin) of subjects achieved target values of A1C (<7%). A total of 10 of the 98 subjects randomized to triple oral therapy (10.2%) who failed to improve sufficiently were switched to insulin therapy. An additional four subjects dropped out of the oral treatment group due to adverse events felt to be potentially drug related. Only two of the subjects randomized to insulin plus metformin had to be switched to basal-bolus regimens (regular insulin and NPH insulin). Cost analysis determined that insulin plus metformin (mean cost 3.20 dollars/day) provided efficacy equal to that of a triple oral drug regimen (10.40 dollars/day). CONCLUSIONS: Insulin 70/30 mix plus metformin was as effective as triple oral therapy in lowering A1C and FPG values. The triple oral regimen was not as cost effective, and a high percentage of subjects (total of 16.3%) did not complete this regimen due to lack of efficacy or side effects.

Administration, Oral↗

PubMedDate not supplied

Pramlintide reduces postprandial glucose excursions when added to insulin lispro in subjects with type 2 diabetes: a dose-timing study.

BACKGROUND: To assess the postprandial glucose-lowering effect of the human amylin analog pramlintide when given with insulin lispro in subjects with type 2 diabetes, with an emphasis on the optimal dose timing relative to meals. METHODS: In this randomized, single-blind, placebo-controlled, five-way crossover study, 19 subjects with type 2 diabetes using insulin lispro underwent five consecutive mixed-meal tests. In randomized order, subjects received subcutaneous injections of placebo at -15 min or 120-microg pramlintide at -15, 0, +15, or +30 min relative to the standardized breakfast after an overnight fast. Insulin lispro was injected at 0 min at doses that were adjusted appropriately for both the content of the standardized meal and the anticipated effects of pramlintide. Plasma glucose concentrations were measured before and during the 4-h postmeal period. RESULTS: When injected at 0 min, pramlintide reduced the postprandial glucose excursion by 81% compared to insulin lispro + placebo (incremental AUC(0-4 h) (mean +/- SE) 2.0 +/- 1.5 vs. 10.4 +/- 2.2 mmol/h/L, P<0.05). When pramlintide was injected at -15, +15, and +30 min, the postprandial incremental glucose AUC(0-4 h) was also significantly reduced (P<0.05), but to a lesser extent (42 to 73%). Pramlintide treatment was well tolerated and no serious adverse events were reported. CONCLUSIONS: Administration of pramlintide either at or just prior to a meal caused a greater reduction in postprandial glucose than either administration of placebo or postmeal pramlintide injections in subjects with type 2 diabetes treated with a rapid-acting insulin analog, insulin lispro.

Adult↗