Grazia Aleppo

Real-time continuous glucose monitoring among participants in the T1D Exchange clinic registry.

OBJECTIVE To assess the frequency of continuous glucose monitoring (CGM) device use, factors associated with its use, and the relationship of CGM with diabetes outcomes (HbA1c, severe hypoglycemia [SH], and diabetic ketoacidosis [DKA]). RESEARCH DESIGN AND METHODS Survey questions related to CGM device use 1 year after enrollment in the T1D Exchange clinic registry were completed by 17,317 participants. Participants were defined as CGM users if they indicated using real-time CGM during the prior 30 days. RESULTS Nine percent of participants used CGM (6% of children <13 years old, 4% of adolescents 13 to <18 years, 6% of young adults 18 to <26 years, and 21% of adults ≥26 years). CGM use was more likely with higher education, higher household income, private health insurance, longer duration of diabetes, and use of insulin pump (P < 0.01 all factors). CGM use was associated with lower HbA1c in children (8.3% vs. 8.6%, P < 0.001) and adults (7.7% vs. 7.9%, P < 0.001). In adults, more frequent use of CGM (≥6 days/week) was associated with lower mean HbA1c. Only 27% of users downloaded data from their device at least once per month, and ≤15% of users reported downloading their device at least weekly. Among participants who used CGM at baseline, 41% had discontinued within 1 year. CONCLUSIONS CGM use is uncommon but associated with lower HbA1c in some age-groups, especially when used more frequently. Factors associated with discontinuation and infrequent use of retrospective analysis of CGM data should be considered in developing next-generation devices and education on CGM use.

Nootropic Drugs Positively Modulate α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid-Sensitive Glutamate Receptors in Neuronal Cultures

Abstract: Micromolar concentrations of piracetam, aniracetam, and oxiracetam enhanced α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)‐stimulated 45Ca2+ influx in primary cultures of cerebellar granule cells. Nootropic drugs increased the efficacy but not the potency of AMPA and their action persisted in the presence of the voltage‐sensitive calcium channel blocker nifedipine. Potentiation by oxiracetam was specific for AMPA receptor‐mediated signal transduction, as the drug changed neither the stimulation of 45Ca2+ influx by kainate or N‐methyl‐d‐aspartate nor the activation of inositol phospholipid hydrolysis elicited by quisqualate or (±)‐1‐aminocyclopentane‐trans‐1,3‐dicarboxylic acid. Piracetam, aniracetam, and oxiracetam increased the maximal density of the specific binding sites for [3H]AMPA in synaptic membranes from rat cerebral cortex. Taken collectively, these results support the view that nootropic drugs act as positive modulators of AMPA‐sensitive glutamate receptors in neurons.

Risk Factors Associated With Severe Hypoglycemia in Older Adults With Type 1 Diabetes

OBJECTIVE Severe hypoglycemia is common in older adults with long-standing type 1 diabetes, but little is known about factors associated with its occurrence. RESEARCH DESIGN AND METHODS A case-control study was conducted at 18 diabetes centers in the T1D Exchange Clinic Network. Participants were ≥60 years old with type 1 diabetes for ≥20 years. Case subjects (n = 101) had at least one severe hypoglycemic event in the prior 12 months. Control subjects (n = 100), frequency-matched to case subjects by age, had no severe hypoglycemia in the prior 3 years. Data were analyzed for cognitive and functional abilities, social support, depression, hypoglycemia unawareness, various aspects of diabetes management, C-peptide level, glycated hemoglobin level, and blinded continuous glucose monitoring (CGM) metrics. RESULTS Glycated hemoglobin (mean 7.8% vs. 7.7%) and CGM-measured mean glucose (175 vs. 175 mg/dL) were similar between case and control subjects. More case than control subjects had hypoglycemia unawareness: only 11% of case subjects compared with 43% of control subjects reported always having symptoms associated with low blood glucose levels (P < 0.001). Case subjects had greater glucose variability than control subjects (P = 0.008) and experienced CGM glucose levels <60 mg/dL for ≥20 min on 46% of days compared with 33% of days in control subjects (P = 0.10). On certain cognitive tests, case subjects scored worse than control subjects. CONCLUSIONS In older adults with long-standing type 1 diabetes, greater hypoglycemia unawareness and glucose variability are associated with an increased risk of severe hypoglycemia. A study to assess interventions to prevent severe hypoglycemia in high-risk individuals is needed.

Metabotropic Glutamate Receptors and Neuronal Toxicity

Specific glutamate receptors coupled to polyphosphoinositide (PPI) hydrolysis have been described in brain slices, cultured neurons, and astrocytes, and in amphibian oocytes injected with rat brain mRNA (Sladeczek et al., 1985; Nicoletti et al., 1986a,b; Sugiyama et al., 1987). In most of the systems, metabotropic receptors are activated by lS,3R-aminocyclopentandicarboxylic acid (ACPD), quisqualate, ibotenate, and L-glutamate, but not by α-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA), kainate, and N-methyl-D-aspartate (NMDA) (Nicoletti et al., 1986a; Schoepp and Johnson, 1988; 1989; Palmer et al., 1989). Trans-ACPD has been described as the most selective agonist of metabotropic receptors (Palmer et al., 1989), although it is less potent than quisqualate in stimulating inositolphosphate formation. In brain slices, stimulation of PPI hydrolysis by metabotropic receptor agonists is extremely high at the earlier stages of postnatal development (within the first 2 weeks after birth) and progressively declines during maturation (Nicoletti et al., 1986a). In adult tissue, the activation of metabotropic receptors is amplified in response to deafferentation (Nicoletti et al., 1987), as well as after induction of long-term potentiation (Aronica et al., 1991) or electrical kindling (Iadarola et al, 1986; Akiyama et al., 1987). Hence, it is likely that metabotropic receptors contribute to the synaptic events involved in the regulation of neuronal plasticity. However, based on the toxic effects of quisqualate in hippocampal slices (Garthwaite and Garthwaite, 1989) and cultured cortical neurons (Patel et al., 1990), a role for metabotropic receptors in the mechanism of neuronal degeneration has been suggested. We have addressed this problem in primary cultures of cerebellar neurons.

REPLACE-BG: A Randomized Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Well-Controlled Type 1 Diabetes

OBJECTIVE To determine whether the use of continuous glucose monitoring (CGM) without confirmatory blood glucose monitoring (BGM) measurements is as safe and effective as using CGM adjunctive to BGM in adults with well-controlled type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS A randomized noninferiority clinical trial was conducted at 14 sites in the T1D Exchange Clinic Network. Participants were ≥18 years of age (mean 44 ± 14 years), had T1D for ≥1 year (mean duration 24 ± 12 years), used an insulin pump, and had an HbA1c ≤9.0% (≤75 mmol/mL) (mean 7.0 ± 0.7% [53 ± 7.7 mmol/mol]); prestudy, 47% were CGM users. Participants were randomly assigned 2:1 to the CGM-only (n = 149) or CGM+BGM (n = 77) group. The primary outcome was time in range (70–180 mg/dL) over the 26-week trial, with a prespecified noninferiority limit of 7.5%. RESULTS CGM use averaged 6.7 ± 0.5 and 6.8 ± 0.4 days/week in the CGM-only and CGM+BGM groups, respectively, over the 26-week trial. BGM tests per day (including the two required daily for CGM calibration) averaged 2.8 ± 0.9 and 5.4 ± 1.4 in the two groups, respectively (P < 0.001). Mean time in 70–180 mg/dL was 63 ± 13% at both baseline and 26 weeks in the CGM-only group and 65 ± 13% and 65 ± 11% in the CGM+BGM group (adjusted difference 0%; one-sided 95% CI −2%). No severe hypoglycemic events occurred in the CGM-only group, and one occurred in the CGM+BGM group. CONCLUSIONS Use of CGM without regular use of confirmatory BGM is as safe and effective as using CGM with BGM in adults with well-controlled T1D at low risk for severe hypoglycemia.

Different responses of gonadotropin-releasing hormone (GnRH) release to glutamate receptor agonists during aging

GnRH release from hypothalamic explants from young and aged male Wistar-Kyoto rats was evaluated following stimulation with glutamate receptor agonists. Glutamate stimulated GnRH release to a similar extent in hypothalami from young and old animals, whereas N-methyl-D-Aspartate (NMDA) and kainate appeared more efficacious in young and old rats, respectively. Old rats were unable to respond to a maximal stimulating concentration of glutamate when they had been previously exposed to a challenge with the same agent. These results demonstrate that responsiveness to glutamate receptor agonists changes during aging, suggesting the involvement of distinct glutamate receptors in the control of GnRH release during different phases of lifespan.

Intensive glycemic control after heart transplantation is safe and effective for diabetic and non-diabetic patients.

Some studies have shown increased mortality, infection, and rejection rates among diabetic (DM) compared to non‐diabetic (non‐DM) patients undergoing heart transplant (HT). This is a retrospective chart review of adult patients (DM, n = 26; non‐DM, n = 66) undergoing HT between June 1, 2005, and July 31, 2009. Glycemic control used intravenous (IV) and subcutaneous (SQ) insulin protocols with a glucose target of 80–110 mg/dL. There were no significant differences between DM and non‐DM patients in mean glucose levels on the IV and SQ insulin protocols. Severe hypoglycemia (glucose <40 mg/dL) did not occur on the IV protocol and was experienced by only 3 non‐DM patients on the SQ protocol. Moderate hypoglycemia (glucose >40 and <60 mg/dL) occurred in 17 (19%) patients on the IV protocol and 24 (27%) on the SQ protocol. There were no significant differences between DM and non‐DM patients within 30 d of surgery in all‐cause mortality, treated HT rejection episodes, reoperation, prolonged ventilation, 30‐d readmissions, ICU readmission, number of ICU hours, hospitalization days after HT, or infections. This study demonstrates that DM and non‐DM patients can achieve excellent glycemic control post‐HT with IV and SQ insulin protocols with similar surgical outcomes and low hypoglycemia rates.

Comparison of Glycemic and Surgical Outcomes After Change in Glycemic Targets in Cardiac Surgery Patients

OBJECTIVE To compare perioperative glycemic and long-term surgical outcomes in patients undergoing cardiac surgery before and after the recommended 2009 changes in inpatient glycemic targets. RESEARCH DESIGN AND METHODS We performed a retrospective review of patients who underwent cardiac surgery between 4 September 2007 and 30 April 2011. Comparison was made of blood glucose (BG) outcomes 3 days after surgery, and 30-day cardiac outcomes before and after a change in insulin protocol that took place on 1 September 2009, which consisted of raising the glycemic targets during intravenous insulin infusions from 80–110 mg/dL (80–110 group) to 110–140 mg/dL (110–140 group). RESULTS When compared with the 80–110 group (n = 667), the 110–140 group (n = 658) had higher mean postoperative BG levels during the intravenous insulin infusion (141 ± 15 vs. 121 ± 15 mg/dL, P < 0.001) and the subcutaneous insulin period (134 ± 24 vs. 130 ± 23 mg/dL, P < 0.001), and for 3 days postoperatively (141 ± 17 vs. 127 ± 15 mg/dL, P < 0.001). Fewer patients in the 110–140 mg/dL group experienced moderate hypoglycemia (BG <70 mg/dL) (177 vs. 73, P = 0.04). Severe hypoglycemia (BG <40 mg/dL) occurred in only one patient in the 80–110 group and three patients in the 110–140 group. There were no significant differences in mortality or surgical complication rates (with the exception of reintubation) between the groups. CONCLUSIONS The higher glycemic target of 110–140 mg/dL resulted in similar mean glucose values, with significantly less hypoglycemia and no significant differences in mortality/morbidity compared with the more strict target of 80–110 mg/dL.

Amyloid β protein does not interact with tachykinin receptors coupled to inositol phospholipid hydrolysis in human astrocytoma cells

We have tested the interaction between amyloid beta protein (A beta P) and tachykinin receptors in cultured UC-11MG astrocytoma cells, which express high affinity substance P receptors and respond to substance P with an unusually large stimulation of polyphosphoinositide hydrolysis. Both the full-length A beta P (A beta P1-40) and the fragment 25-35 (A beta P25-35) did not affect the stimulation of [3H]inositolmonophosphate (InsP) formation by substance P. A beta P25-35 was also inactive when applied to the cultures 18 or 72 h prior to the assay. In addition, A beta P25-35 did not displace specifically bound [3H]SarMet substance P from its recognition sites in intact UC-11MG cells. These results suggest that, at least in this specific cell type, amyloid peptides do not interact with substance P receptors.

Use of Adjuvant Pharmacotherapy in Type 1 Diabetes: International Comparison of 49,996 Individuals in the Prospective Diabetes Follow-up and T1D Exchange Registries

The majority of those with type 1 diabetes (T1D) have suboptimal glycemic control (1–4); therefore, use of adjunctive pharmacotherapy to improve control has been of clinical interest. While noninsulin medications approved for type 2 diabetes have been reported in T1D research and clinical practice (5), little is known about their frequency of use. The T1D Exchange (T1DX) registry in the U.S. and the Prospective Diabetes Follow-up (DPV) registry in Germany and Austria are two large consortia of diabetes centers; thus, they provide a rich data set to address this question. For the analysis, 49,996 pediatric and adult patients with diabetes duration ≥1 year and a registry update from 1 April 2015 to 1 July 2016 were included (19,298 individuals from 73 T1DX sites and 30,698 individuals from 354 DPV sites). Adjuvant medication use (metformin, glucagon-like peptide 1 [GLP-1] receptor agonists, dipeptidyl peptidase 4 [DPP-4] inhibitors, sodium–glucose cotransporter 2 [SGLT2] inhibitors, and other noninsulin diabetes medications including pramlintide) was extracted from …