Dataset Information

Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes During Treatment with a SGLT2 Inhibitor: An Insulin Pump Suspension Study.

ABSTRACT: BACKGROUND:Enthusiasm for the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as an adjunctive treatment in type 1 diabetes (T1D) has been offset by the possible increased risk of diabetic ketoacidosis (DKA). Since pump-treated T1D patients are susceptible to DKA due to infusion site problems, this study was undertaken to assess how treatment with SGLT2i affects patterns of early metabolic decompensation following suspension of basal insulin. METHODS:Ten T1D participants (age 19-35 years, duration 10?±?8 years, A1c 7.4%?±?0.8%) underwent overnight pump suspension studies before and after treatment with canagliflozin (CANA). On both nights, basal insulin was suspended at 3 AM and plasma glucose (PG), ?-hydroxybutyrate (BHB), free fatty acids (FFA), plasma insulin (PI), and glucagon were measured. Studies were terminated 6?h after suspension or if PG rose to >350?mg/dL or BHB >2.5?mmol/L. RESULTS:PI levels at the start of suspension were reduced by 30% after CANA treatment (44?±?11?uU/mL vs. 31?±?10?uU/mL, P?

SUBMITTER: Patel NS

PROVIDER: S-EPMC5689123 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes During Treatment with a SGLT2 Inhibitor: An Insulin Pump Suspension Study.

Patel Neha S NS Van Name Michelle A MA Cengiz Eda E Carria Lori R LR Weinzimer Stuart A SA Tamborlane William V WV Sherr Jennifer L JL

Diabetes technology & therapeutics 20171025 11

<h4>Background</h4>Enthusiasm for the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as an adjunctive treatment in type 1 diabetes (T1D) has been offset by the possible increased risk of diabetic ketoacidosis (DKA). Since pump-treated T1D patients are susceptible to DKA due to infusion site problems, this study was undertaken to assess how treatment with SGLT2i affects patterns of early metabolic decompensation following suspension of basal insulin.<h4>Methods</h4>Ten T1D partici ...[more]

PMID: 29068709

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Project description:BackgroundMetabolic syndrome (MetS) is a prevalent risk factor for cardiac dysfunction. Although SGLT2-inhibitors have important cardioprotective effects in hyperglycemia, their underlying mechanisms are complex and not completely understood. Therefore, we examined mechanisms of a SGLT2-inhibitor dapagliflozin (DAPA)-related cardioprotection in overweight insulin-resistant MetS-rats comparison with insulin (INSU), behind its glucose-lowering effect.MethodsA 28-week high-carbohydrate diet-induced MetS-rats received DAPA (5 mg/kg), INSU (0.15 mg/kg) or vehicle for 2 weeks. To validate MetS-induction, we monitored all animals weekly by measuring body weight, blood glucose and HOMO-IR index, electrocardiograms, heart rate, systolic and diastolic pressures.ResultsDAPA-treatment of MetS-rats significantly augmented the increased blood pressure, prolonged Q-R interval, and low heart rate with depressed left ventricular function and relaxation of the aorta. Prolonged-action potentials were preserved with DAPA-treatment, more prominently than INSU-treatment, at most, through the augmentation in depressed voltage-gated K+-channel currents. DAPA, more prominently than INSU-treatment, preserved the depolarized mitochondrial membrane potential, and altered mitochondrial protein levels such as Mfn-1, Mfn-2, and Fis-1 as well as provided significant augmentation in cytosolic Ca2+-homeostasis. Furthermore, DAPA also induced significant augmentation in voltage-gated Na+-currents and intracellular pH, and the cellular levels of increased oxidative stress, protein-thiol oxidation and ADP/ATP ratio in cardiomyocytes from MetS rats. Moreover, DAPA-treatment normalized the increases in the mRNA level of SGLT2 in MetS-rat heart.ConclusionsOverall, our data provided a new insight into DAPA-associated cardioprotection in MetS rats, including suppression of prolonged ventricular-repolarization through augmentation of mitochondrial function and oxidative stress followed by improvement of fusion-fission proteins, out of its glucose-lowering effect.

Project description:BACKGROUND:This prospective single-center study recruited insulin-resistant continuous subcutaneous insulin infusion (CSII) therapy-naive patients with type 2 diabetes (T2D) using insulin analog-based multiple daily injections (MDI) therapy and metformin. METHODS:A total of 23 individuals with T2D (70% male), aged a mean?±?standard deviation 57.2?±?8.03 years, with body mass index of 36.2?±?7.02?kg/m2, diabetes duration of 13.3?±?4.64 years, and HbA1c of 10.0%?±?1.05% were randomly assigned to a CSII arm or an MDI continuation arm to explore glucose control, weight loss, total daily insulin dose (TDD), and insulin resistance. Insulin dosing was optimized over a 2-month run-in period. RESULTS:At 6 months, patients assigned to the CSII arm achieved a significant mean HbA1c reduction of -0.9% (95% confidence interval [CI]?=?-1.6, -0.1), while reducing their TDD by -29.8?±?28.41?U/day (33% of baseline [92.1?±?20.35?U/day]) and achieving body mass (BM) reduction of -0.8?±?5.61?kg (0.98% of baseline [104.8?±?16.15?kg]). MDI patients demonstrated a nonsignificant HbA1c reduction of -0.3% (95% CI?=?-0.8, 0.1) with a TDD reduction of 5% from baseline (99.0?±?25.25?U/day to 94.3?±?21.25?U/day), and a BM reduction of -1.0?±?2.03?kg (0.99% of baseline [108.9?±?20.55?kg]). After 6 months, the MDI arm crossed over to CSII therapy. At 12 months, patients continuing CSII demonstrated an additional mean 0.7% HbA1c reduction with 54.6% achieving HbA1c<8%. The final TDD reduction was -9.7?U/day in comparison to baseline; BM increased by 1.1?±?6.5?kg from baseline. The MDI patients that crossed to CSII showed an HbA1c reduction of -0.5%?±?1.04%, HbA1c response rate of 27.3%, a TDD reduction of -17.4?±?21.06?U/day, and a BM reduction of -0.3?±?3.39?kg. Diabetic ketoacidosis or severe hypoglycemia did not occur in either arm. CONCLUSION:CSII therapy safely and significantly improved metabolic control with less insulin usage, with no sustainable reduction of BM, blood pressure, and lipid profile, in insulin-resistant T2D patients. Treatment adherence and satisfaction in these patients were excellent.

Dataset Information

Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes During Treatment with a SGLT2 Inhibitor: An Insulin Pump Suspension Study.

Publications

Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes During Treatment with a SGLT2 Inhibitor: An Insulin Pump Suspension Study.

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