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Diabetes Technology & Therapeutics 02/2013; 15 Suppl 1:S3-S12. · 1.93 Impact Factor
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ABSTRACT: Objective Peripheral insulin resistance in type 1 diabetes may be related to a paradoxical postprandial glucagon increase. This study evaluated the effects of sitagliptin, (DPP-IV inhibitor, approved for patients with type 2 diabetes), in adults with type 1 diabetes to improve glycemic control through decreasing postprandial glucagon.Methods This investigator-initiated, double-blind, randomized-parallel 20-week study enrolled 141 subjects. Subjects received sitagliptin 100 mg/day or placebo for 16-weeks. A subset of 85 patients wore blinded continuous glucose monitors (CGM) for 5 separate 7-day periods. The primary outcome was post-meal (Boost™) reduction in 4-hour glucagon area under the curve (AUC). Secondary endpoints included changes in A1c, CGM data, insulin dose, GLP-1, GIP, and C-peptide levels.Results There were no differences at screening between groups; however, after 4-week run-in phase, A1c was significantly lower in the sitagliptin vs. placebo group. Post-meal GLP-1 levels were higher (P<0.001) and GIP levels lower (P=0.03), with glucagon suppression at 30 minutes (LS means 23.2 ± 1.9 vs. 16.0 ± 1.8, P=0.006) in the sitagliptin group at 16-weeks. There were no differences between the groups in change in A1c, insulin dose, weight, or C-peptide after 16-weeks of treatment. However, C-peptide positive patients randomized to sitagliplin had a non-significant trend toward decrease in A1c, mean glucose and time spent in hyperglycemia.Conclusion Sitagliptin use in type 1 diabetes did not change glucagon AUC, A1c, insulin dose or weight despite post-meal rise in GLP-1 levels. C-peptide positive subjects treated with sitagliptin had a non-significant trend in decreasing hyperglycemia which needs further evaluation.
Endocrine Practice 11/2012; · 2.49 Impact Factor
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ABSTRACT: There has been a significant increase in the prevalence of type 1 diabetes mellitus and type 2 diabetes mellitus in the past decade. The International Diabetes Foundation reported that there will be more than a half-billion people with diabetes by 2030, largely in emerging economies. Improved glucose control reduces microvascular and macrovascular complications and can be accomplished with intensive diabetes management. Continuous glucose monitors allow further improvement. The best way to emulate normal physiology is the development of an artificial pancreas. Early versions of closed-loop technology may be available in the United States in the next 3 to 5 years.
Endocrinology and metabolism clinics of North America 03/2012; 41(1):89-104. · 3.56 Impact Factor
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ABSTRACT: The prevalence of diabetes is increasing globally and is expected to increase to 439 million people by the year 2030. Several studies have shown that improved glycemic control measured by glycosylated hemoglobin (A1c) in patients with type 1 and type 2 diabetes results in a reduction of both the micro- and macrovascular complications associated with the disease. The recent introduction of new oral medications, insulin analogs (long and rapid acting), insulin pens and pumps, better SMBG meters and continuous glucose monitoring (CGM) have all resulted in improvement of glycemic control. Closed-loop devices currently in development aim to integrate the CGM and pump system in order to more closely mimic the human pancreas. The other upcoming new basal insulin (Degludec), prandial insulin, other new technologies and improved oral therapies will significantly improve patient acceptance of intensive therapy, glycemic control and quality of life in patients with diabetes.
Diabetes research and clinical practice 02/2012; 97(1):16-26. · 2.16 Impact Factor
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Satish K Garg
Diabetes Technology & Therapeutics 11/2011; 14(1):1-2. · 1.93 Impact Factor
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Diabetes Technology & Therapeutics 06/2011; 13 Suppl 1:S1-4. · 1.93 Impact Factor
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Satish K Garg
Diabetes Technology & Therapeutics 03/2011; 13(3):295. · 1.93 Impact Factor
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ABSTRACT: To compare use of continuous glucose monitoring in subjects with type 1 diabetes on multiple daily injection (MDI) therapy versus continuous subcutaneous insulin infusion (CSII) therapy for 6 months.
Sixty type 1 diabetic adults with similar baseline characteristics, using either MDI (n = 30) or CSII (n = 30) therapy, were enrolled in this 6-month prospective study. Subjects were instructed to wear the DexCom SevenPLUS continuous glucose monitor at all times throughout the study. All subjects were initially blinded from the continuous glucose monitoring (CGM) glucose data. After 4 weeks of blinded CGM use, the CGM was unblinded, making glucose data available to the patient. The CGM remained in the unblinded state for the remainder of the study (20 weeks). Clinic visits occurred every 4 weeks, at which time A1C values were collected and CGM data were downloaded.
Mean baseline (± SD) A1C was 7.61 (± 0.76) and 7.63 (± 0.68) for CSII and MDI, respectively (P > 0.05). Without any significant therapy change, A1C decrease at 12 weeks was similar in both groups (P = 0.03). When compared with the blinded phase, unblinded use of CGM was associated with similar but significant reductions in glycemic control and variability parameters. In addition, both therapy groups had similar changes in mean glucose and glucose variability indexes at 3 and 6 months (ITT analysis, P > 0.05). Predefined per protocol analysis (sensor use at least 6 days/week) showed greater improvement in time spent in target range glycemia, 3.9-10.0 mmol/L (70-180 mg/dL), in the CSII group.
We conclude that CGM provides similar benefits in glucose control for patients using MDI or CSII therapy.
Diabetes care 01/2011; 34(3):574-9. · 8.09 Impact Factor
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ABSTRACT: The objective of this study is to examine the relationship among serum levels of 25-hydroxyvitamin D (25[OH]D), polymorphisms in vitamin D-associated genes, and the presence and progression of coronary artery calcification (CAC) in adults with type 1 diabetes.
This prospective study included 374 non-Hispanic white individuals with type 1 diabetes (mean age 40 ± 9 years; 46% were male). CAC was measured at the baseline and 3- and 6-year follow-up visits were determined by electron beam computed tomography. Serum 25[OH]D levels were measured by liquid chromatography tandem mass spectrometry at the 3-year visit.
Normal (>30 ng/mL), insufficient (20-30 ng/mL), and deficient (<20 ng/mL) 25-[OH]D levels were present in 65%, 25%, and 10% of the individuals with type 1 diabetes, respectively. 25[OH]D deficiency was associated with the presence of CAC at the 3-year visit, odds ratio (OR) = 3.3 (95% CI 1.6-7.0), adjusting for age, sex, and hours of daylight. In subjects free of CAC at the 3-year visit, 25[OH]D deficiency predicted the development of CAC over the next 3 years in those with the vitamin D receptor M1T CC genotype (OR = 6.5 [1.1-40.2], P = 0.04) than in those with the CT or TT genotype (OR = 1.6 [0.3-8.6], P = 0.57).
Vitamin D deficiency independently predicts prevalence and development of CAC, a marker of coronary artery plaque burden, in individuals with type 1 diabetes.
Diabetes care 10/2010; 34(2):454-8. · 8.09 Impact Factor
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Satish K Garg
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ABSTRACT: The treatment of type 2 diabetes mellitus (T2DM) has been revolutionized by the introduction of novel therapeutic regimens following the clinical approval of the long-acting basal insulin glargine 10 years ago, followed by insulin detemir and, more recently, agents that target the glucagon-like peptide (GLP)-1 system with dipeptidyl peptidase 4 (DPP-4)-resistant products, such as liraglutide and exenatide, and DPP-4 inhibitors, such as sitagliptin, saxagliptin, alogliptin, and vildagliptin. The position and clinical efficacy of the GLP-1 mimetics are less well understood, however, and how they should be best used in the context of the established clinical efficacy of long-acting insulin analogs is yet to be defined. The aim of this review is to provide a summary of the efficacy, safety, and weight changes associated with long-acting insulin analogs (insulin glargine and insulin detemir) and two GLP-1 mimetics (exenatide and liraglutide). MEDLINE, EMBASE, and BIOSIS databases were searched with a timeframe of January 1, 2003-January 12, 2009 using the following terms: "Insulin glargine," with the co-indexing terms "LANTUS" and "HOE901"; "Insulin detemir," with the co-indexing term "Levemir"; "Exenatide"; and "Liraglutide." This literature review demonstrates that GLP-1 and basal insulin therapies are effective treatment options for insulin-naïve patients with suboptimal glycemic control with oral hypoglycemic agents. There are potential advantages of basal insulin and GLP-1 therapies in particular populations of patients. Further comparative data are needed to fully investigate the relative positioning of these therapies within the T2DM treatment paradigm.
Diabetes Technology & Therapeutics 01/2010; 12(1):11-24. · 1.93 Impact Factor
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ABSTRACT: To evaluate the system time lag associated with subcutaneous interstitial glucose (IG) sensing and venous blood glucose (BG) of two continuous glucose monitoring (CGM) systems, the SEVEN((R)) (DexCom, San Diego, CA) and the Navigator((R)) (Abbott Diabetes Care, Alameda, CA), in adults with type 1 diabetes.
Fourteen subjects wore both CGM systems concurrently during the 15-day study. Reference YSI (Yellow Springs, OH) and CGM data from the in-clinic sessions, conducted on day 5, 10 and 15 of the study were evaluated. The system time lag of CGM system was estimated using various regression method related statistical estimators.
The estimated time lags based on different statistical measures are similar within each CGM system. The time lag based on correlation coefficient criteria is estimated as 4.5+/-5min (median+/-IQR) for the SEVEN((R)), and 15+/-7min for the Navigator((R)). The ranges of these estimators of two CGM systems were different (2-6min for SEVEN((R)) and 14-15min for Navigator((R))).
The study findings suggest that commonly accessible statistics, such as correlation statistics, offer estimates that are comparable to complicated approaches. Different time lags were observed with two CGM systems.
Diabetes research and clinical practice 12/2009; 87(3):348-53. · 2.16 Impact Factor
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ABSTRACT: We compared changes in response to unmasking of continuous glucose monitoring (CGM) in subjects with type 1 diabetes who use multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII).
Use of real-time CGM (DexCom [San Diego, CA] SEVEN was studied in 38 subjects using CSII and 26 using MDI. CGM output was masked during Week 1 and unmasked during Weeks 2 and 3. We evaluated changes in 16 criteria for quality of glycemic control and eight criteria for glycemic variability.
All 24 criteria showed highly statistically significant improvement when considered simultaneously (P < 0.000001). For subjects using CSII, 18 of 24 criteria improved significantly (nominal P < 0.05); for subjects using MDI, 16 of 24 criteria improved significantly (P < 0.05). Twelve of the comparisons remained significant (P < 0.05) after applying the overconservative Bonferroni correction for multiple comparisons. The percentage of glucose values within the range 80-140 mg/dL increased by 19% and 17% relative to their control values (Week 1) for subjects using MDI and CSII, respectively. Mean glucose, overall SD (SD(T)), SD between daily means (SD(dm)), mean amplitude of glycemic excursion (MAGE), and mean of daily differences (MODD) improved significantly. Responses to CGM display were not significantly different between the MDI and CSII subject groups for any of the 24 criteria considered individually or in groups of eight, 16, or 24.
CGM has similar effectiveness in subjects with type 1 diabetes using either CSII or MDI.
Diabetes Technology & Therapeutics 12/2009; 11(12):757-65. · 1.93 Impact Factor
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ABSTRACT: We evaluated effects of unmasking of continuous display of continuous glucose monitoring (CGM) on quality of glycemic control and glycemic variability.
We reanalyzed CGM data from 85 patients using a 7-day glucose sensor. Glucose values were "masked" during the first week but "unmasked" during the next 2 weeks. We evaluated 48 criteria for quality of glycemic control, including mean glucose, SD, percentage of values within-, above- or below- specified ranges, Schlichtkrull's M(100) index, mean amplitude of glycemic excursion (MAGE), mean of daily differences (MODD), the J index, "Index of Glycemic Control" (IGC), Hyperglycemia Index, Hypoglycemia Index, High Blood Glucose Index (HBGI), Low Blood Glucose Index (LBGI), average daily risk range (ADRR), GRADE scores, and CONGA(n). We calculated SD values between daily means, between days-within time points, within days, between time points (for the average glucose profile for several days), and within series for time segments of arbitrary length.
Unmasking CGM displays resulted in rapid, highly statistically significant improvement in 29 indices, including percentage within, percentage above, and percentage below target range, mean glucose, SD, SD of daily means, MODD, M(100), IGC, GRADE, HBGI, and J index. Both hyperglycemia and hypoglycemia improved during the first week after unmasking; further improvement in hypoglycemia was seen during the following week. Results obtained using multiple criteria were consistent and highly correlated.
Continuous access to display of CGM sensors dramatically improved 29 indices of glycemic control and glycemic variability.
Diabetes Technology & Therapeutics 11/2009; 11(11):717-23. · 1.93 Impact Factor
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Diabetes Technology & Therapeutics 09/2009; 11 Suppl 2:S1-3. · 1.93 Impact Factor
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ABSTRACT: Patients with type 1 diabetes require intensive insulin therapy for optimal glycemic control. AIR((R)) inhaled insulin (system from Eli Lilly and Company, Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) may be an efficacious and safe alternative to subcutaneously injected (SC) mealtime insulin.
This was a Phase 3, 2-year, randomized, open-label, active-comparator, parallel-group study in 385 patients with type 1 diabetes who were randomly assigned to receive AIR insulin or SC insulin (regular human insulin or insulin lispro) at mealtimes. Both groups received insulin glargine once daily. Efficacy measures included mean change in hemoglobin A1C (A1C) from baseline to end point, eight-point self-monitored blood glucose profiles, and insulin dosage. Safety assessments included hypoglycemic events, pulmonary function tests, adverse events, and insulin antibody levels.
In both treatment groups, only 20% of subjects reached the target of A1C <7.0%. A significant A1C difference of 0.44% was seen favoring SC insulin, with no difference between the groups in insulin doses or hypoglycemic events at end point. Patients in both treatment groups experienced progressive decreases in lung function, but larger (reversible) decrements in diffusing capacity of the lung for carbon monoxide (DL(CO)) were associated with AIR insulin treatment. Greater weight gain was seen with SC insulin treatment.
The AIR inhaled insulin program was terminated by the sponsor prior to availability of any Phase 3 data for reasons unrelated to safety or efficacy. Despite early termination, this trial provides evidence that AIR insulin was less efficacious in lowering A1C and was associated with a greater decrease in DL(CO) and increased incidence of cough than SC insulin in patients with type 1 diabetes.
Diabetes Technology & Therapeutics 09/2009; 11 Suppl 2:S5-S16. · 1.93 Impact Factor
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ABSTRACT: This study evaluated the accuracy and safety of two continuous glucose monitoring (CGM) systems, the SEVEN (DexCom, San Diego, CA) and the Navigator (Abbott Diabetes Care, Alameda, CA), with the YSI laboratory measurements of blood glucose (blood glucose meter manufactured by YSI, Yellow Springs, OH), when worn concurrently in adults with type 1 diabetes.
Fourteen subjects with type 1 diabetes, 33 +/- 6 (mean +/- SD) years old, were enrolled in this study. All subjects wore both sensors concurrently over three consecutive 5-day CGM sessions (15-day wear). On Days 5, 10, and 15, subjects participated in an 8-h in-clinic session where measurements from the CGM systems were collected and compared with YSI measurements every 15 min. At the end of Day 5 and 10 in-clinic sessions, the sensors were removed, and new sensors were inserted for the following CGM session despite the SEVEN system's recommended use for up to 7 days.
The mean absolute relative difference (ARD) for the two CGM devices versus YSI was not different: 16.8% and 16.1% for SEVEN and Navigator, respectively (P = 0.38). In the hypoglycemic region (YSI value <80 mg/dL), the mean ARD for SEVEN was lower than for Navigator (21.5% vs. 29.8%, respectively; P = 0.001). The data analyses were similar when compared with self-monitoring of blood glucose (SMBG) values. Thirteen additional Navigator replacement devices were issued compared to two for the SEVEN. A total of three versus 14 skin reactions were reported with the SEVEN and Navigator insertion area, respectively.
Glucose measurements with the SEVEN and Navigator were found to be similar compared with YSI and SMBG measurements, with the exception of the hypoglycemic range where the SEVEN performed better. However, the Navigator caused more skin area reactions.
Diabetes Technology & Therapeutics 02/2009; 11(2):65-72. · 1.93 Impact Factor
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ABSTRACT: The purpose of this pilot study was to evaluate the feasibility of 10-day use of a transcutaneous, real-time, continuous glucose-monitoring (CGM) system. All previous reports using different CGM systems were for 3-, 5-, or 7-day use.
On day 1, subjects received the CGM device (SEVEN System) and underwent training on proper use. Subjects returned to the clinic on days 2, 7, and 10 for in-clinic sessions. On days 2 and 7, half the subjects performed fingersticks every 15 min and the other half had Yellow Springs Instruments (YSI) samples drawn every 15 min. On day 10, all subjects participated in an 8-h in-clinic session with YSI and fingerstick testing.
The median absolute relative difference for CGM versus YSI was 12.6, 11.3, and 14.5% on days 2, 7, and 10, respectively (P = 0.63). CGM performed better on day 10 when compared with self-monitoring of blood glucose as compared with YSI.
This is the first study to document 10-day use of a 7-day CGM system.
Diabetes care 12/2008; 32(3):436-8. · 8.09 Impact Factor
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Satish K Garg
Diabetes Technology & Therapeutics 11/2008; 10(5):413-4. · 1.93 Impact Factor
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Diabetes Technology & Therapeutics 11/2008; 10(5):331-2. · 1.93 Impact Factor
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ABSTRACT: Management of type 1 diabetes could be significantly improved with the availability of computerized insulin algorithms for home use.
This was a 1-year open label randomized control trial involving 123 adult subjects with type 1 diabetes (hemoglobin A1c values 7.5-11%) assigned to either the insulin guidance software (ACCU-CHEK) [Roche, Indianapolis, IN] Advisor) for personal data assistant (experimental group) or the control group. The primary aim of the study was to see if subjects using insulin dosing advisor software will improve glucose control over 1 year. The principal end point was an improvement in A1c at 6 and 12 months by >or=0.4%.
Baseline demographics were similar in the two groups. Mean A1c was 8.54+/-0.11% in the control group and 8.42+/-0.11% (P=0.4265) in the experimental group. The mean A1c was significantly lower from 3 to 12 months in the experimental group (P<0.02). A1c reduction of >or=0.6% was maintained at 12 months in the experimental group. Also, a significantly higher number of subjects achieved A1c <7.5% in the experimental group from 3 to 9 months. Within target range glycemia (70-150 mg/dL) was higher in the experimental group at 3-9 months without any change in insulin dose or weight. Above target range glycemia was lower in the experimental group throughout the study. Frequency of testing per day was higher in the experimental group. Nocturnal hypoglycemia was not different between groups; however, the experimental group experienced more severe hypoglycemic events.
This is the first report that shows improved glycemic control can be maintained over 12 months in patients with type 1 diabetes by using Advisor with no change in insulin dose and weight.
Diabetes Technology & Therapeutics 11/2008; 10(5):369-75. · 1.93 Impact Factor
