Hypoglycemia In Type 1 Diabetes Research Articles

Interrupting prolonged sitting with frequent short bouts of light-intensity activity in people with type 1 diabetes improves glycaemic control without increasing hypoglycaemia: The SIT-LESS randomised controlled trial.

To examine the impact of interrupting prolonged sitting with frequent short bouts of light-intensity activity on glycaemic control in people with type 1 diabetes (T1D). In total, 32 inactive adults with T1D [aged 27.9 ± 4.7 years, 15 men, diabetes duration 16.0 ± 6.9 years and glycated haemoglobin 8.4 ± 1.4% (68 ± 2.3 mmol/mol)] underwent two 7-h experimental conditions in a randomised crossover fashion with >7-day washout consisting of: uninterrupted sitting (SIT), or, interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals (SIT-LESS). Standardised mixed-macronutrient meals were administered 3.5 h apart during each condition. Blinded continuous glucose monitoring captured interstitial glucose responses during the 7-h experimental period and for a further 48-h under free-living conditions. SIT-LESS reduced total mean glucose (SIT 8.2 ± 2.6 vs. SIT-LESS 6.9 ± 1.7 mmol/L, p = .001) and increased time in range (3.9-10.0 mmol/L) by 13.7% (SIT 71.5 ± 9.5 vs. SIT-LESS 85.1 ± 7.1%, p = .002). Hyperglycaemia (>10.0 mmol/L) was reduced by 15.0% under SIT-LESS (SIT 24.2 ± 10.8 vs. SIT-LESS 9.2 ± 6.4%, p = .002), whereas hypoglycaemia exposure (<3.9 mmol/L) (SIT 4.6 ± 3.0 vs. SIT-LESS 6.0 ± 6.0%, p = .583) was comparable across conditions. SIT-LESS reduced glycaemic variability (coefficient of variation %) by 7.8% across the observation window (p = .021). These findings were consistent when assessing discrete time periods, with SIT-LESS improving experimental and free-living postprandial, whole-day and night-time glycaemic outcomes (p < .05). Interrupting prolonged sitting with frequent short bouts of light-intensity activity improves acute postprandial and 48-h glycaemia in adults with T1D. This pragmatic strategy is an efficacious approach to reducing sedentariness and increasing physical activity levels without increasing risk of hypoglycaemia in T1D.

Continuous Glucose Monitoring-Recorded Hypoglycemia with Insulin Degludec or Insulin Glargine U100 in People with Type 1 Diabetes Prone to Nocturnal Severe Hypoglycemia.

Background and Aims: Nocturnal hypoglycemia is mainly a consequence of inappropriate basal insulin therapy in type 1 diabetes (T1D) and may compromise optimal glycemic control. Insulin degludec is associated with a lower risk of nocturnal hypoglycemia in T1D. As nocturnal hypoglycemia is often asymptomatic, we applied continuous glucose monitoring (CGM) to detect a more precise occurrence of nocturnal hypoglycemia in the HypoDeg trial, comparing insulin degludec with insulin glargine U100 in people with T1D and previous nocturnal severe hypoglycemia. Materials and Methods: In the HypoDeg trial, 149 people with T1D were included in an open-label randomized cross-over trial. Sixty-seven participants accepted optional participation in the predefined substudy of 4 × 6 days of blinded CGM requiring completion of at least one CGM period in each treatment arm. CGM data were reviewed for hypoglycemic events. Results: Treatment with insulin degludec resulted in a relative rate reduction (RRR) of 36% (95% confidence interval [CI]: 10%-54%; P < 0.05) in nocturnal CGM-recorded hypoglycemia (≤3.9 mmol/L), corresponding to an absolute rate reduction (ARR) of 0.85 events per person-week. In nocturnal CGM-recorded hypoglycemia (≤3.0 mmol/L), we found an RRR of 53% (95% CI: 36%-65%; P < 0.001), corresponding to an ARR of 0.75 events per person-week. At the lower detection limit of the CGM (≤2.2 mmol/L), treatment with insulin degludec resulted in a significant RRR of 58% (95% CI: 23%-77%; P = 0.005). The reductions were primarily due to significant RRRs in asymptomatic hypoglycemia. Conclusion: In people with T1D, prone to nocturnal severe hypoglycemia, insulin degludec compared with insulin glargine U100 significantly reduces nocturnal CGM-recorded hypoglycemia. www.clinicaltrials.gov (#NCT02192450).

Sleep and hypoglycaemia symptom perception in adults with type-1 diabetes mellitus: A mixed-methods review.

The study aims to review, synthesize and integrate primary research on the relationship between sleep and hypoglycaemia symptom perception in adults with type-1 diabetes. This mixed-methods review follows a convergent segregated approach to synthesis and integration of qualitative and quantitative evidence. With assistance of a biomedical librarian, a search of four databases was conducted (PubMed, CINAHL, Embase and PsycINFO) in June 2020. The review included primary research measuring sleep and hypoglycaemia symptom perception in adults (age≥18years) with type-1 diabetes in English. Studies that exclusively addressed children, type-2 diabetes or outcomes unrelated to sleep and hypoglycaemia symptom perception were excluded. Screening focused on title and abstract review (n=624). Studies not excluded after screening (n=35) underwent full-text review. References of each study selected for inclusion (n=6) were hand searched with one study added. All studies included in the review (n=7) were critically appraised with JBI Critical Appraisal tools, and then data were extracted with systematic evaluation. Quantitative synthesis found sleep reduces the magnitude of detectable symptoms and one's capacity to detect them. Qualitative synthesis found that individuals with type-1 diabetes perceive unpredictable severity, frequency and awareness of symptoms while asleep as an oppressive, lingering threat. Integration of findings highlights the troublesome duality of sleep's relationship with hypoglycaemia symptom perception. Sleep presents a challenging time for individuals with type-1 diabetes. Further research examining the relationship between sleep and hypoglycaemia symptom perception is recommended as the number of studies limits this review. Symptom perception is the main physiologic defense against severe hypoglycaemia in type-1 diabetes. This review found that sleep's relationship with hypoglycaemia symptoms has unique physiological and psychological components to address when providing comprehensive care. This review may inform future lines of inquiry that develop into interventions, improvements in practice and risk reduction for hypoglycaemia-related complications.

48-OR: Changes in Global Cerebral Blood Flow in Response to Hypoglycemia in Type 1 Diabetes Do Not Influence Awareness Status

Changes in global cerebral blood flow (gCBF) have been suggested as a mechanism for mitigating the functional impact of hypoglycemia on the brain. The impact of type 1 diabetes (T1D) or hypoglycemia awareness status is not clear. We measured gCBF during progressive lowering of plasma glucose in people with and without T1D, and with retained or impaired awareness of hypoglycemia. Methods: Fifty-one participants (15 with no diabetes (ND), 15 with T1D and normal awareness of hypoglycemia (NAH) and 21 with T1D and impaired awareness of hypoglycemia (IAH)) underwent a two-step hyperinsulinemic hypoglycemic clamp. gCBF was estimated using pseudocontinuous arterial spin labelling magnetic resonance imaging at 6 timepoints: 2 euglycemic, two in the descent phase and two hypoglycemic. gCBF was extracted using a global grey matter mask in SPM12. Statistical analysis and thresholded linear models were performed in R. Results: The mean (+ SD) glucose values at the six timepoints were 95.8 (8.0), 95.5 (9.2), 55.0 (8.3), 50.8 (5.3), 45.7 (4.3) and 45.8 (4.0) mg/dL. Symptom responses to hypoglycemia were absent in IAH. There was a significant increase in CBF in response to hypoglycemia (3-way ANOVA p = 0.04). This was driven by responses in NAH (+7.3%, p &amp;lt; 0.05) and IAH (+10.6% p &amp;lt; 0.01) with no response in ND (+3.5% p = 0.16). The response was not linear, with glucose thresholds of 55.8 mg/dL in NAH and 54.0 mg/dL in IAH (pNAH vs IAH = 0.9) with no threshold in ND. Conclusion: In people with T1D, there is a non-linear relationship between falling glucose and rising gCBF which is not related to awareness status and is not seen in health. The threshold glucose between 54 and 56 mg/dL corresponds closely with level 2 hypoglycemia cut-offs used in current clinical practice. We propose that there is a failure of cerebral vascular autoregulation in response to hypoglycemia in T1D. gCBF responses to hypoglycemia in T1D are independent of symptomatic responses and not responsible for lack of hypoglycemia awareness. Disclosure P. Jacob: None. O. Odaly: None. S. A. Amiel: Advisory Panel; Self; Diabetes UK, Medtronic, Other Relationship; Self; Sanofi, Research Support; Self; Diabetes UK, European Union, JDRF. P. Choudhary: Advisory Panel; Self; Abbott Diabetes, Insulet Corporation, Lilly Diabetes, Medtronic, Sanofi-Aventis, Speaker’s Bureau; Self; Dexcom, Inc., Novo Nordisk. Funding JDRF (3-SRA-2017-484-S-B)

322-OR: SGLT2 Inhibition Has No Effect on the Counterregulatory Response to Hypoglycemia in Subjects with Type 1 Diabetes (T1D)

Individuals with T1D have an ineffective glucagon response to low glucose levels which predisposes them to episodes of hypoglycemia. SGLT-2 inhibitors (SGLT2i) do not increase and may even reduce hypoglycemia in clinical trials, yet the mechanism is unknown. This trial was conducted to determine if SGLT2i improve the counterregulatory response (CR) to hypoglycemia. Subjects with T1D (n=22) received 4 weeks of SGLT2i (dapagliflozin 5 mg daily) and 4 weeks of placebo in a double-blind, random-order, cross-over study. After each phase, subjects underwent a hypoglycemic clamp. During 40 min of hypoglycemia (mean serum glucose 49 mg/dL) CR hormones were serially measured. There was no difference between treatment phases in glucagon or other CR hormones during hypoglycemia [Figure]. Mean ± SE (paired two-tailed t-test) during hypoglycemia for SGLT2i vs. Placebo were: Glucagon (15.4 ± 1.8 vs. 14.8 ± 2.1 pg/mL; P = 0.77), Epinephrine (216 ± 34 vs. 200 ± 28 pg/mL; P = 0.46), Norepinephrine (402 ± 39 vs. 381 ± 25 pg/mL; P = 0.51), GH (9.1 ± 1.3 vs. 8.4 ± 1.8 ng/mL; P = 0.60), and Cortisol (11.4 ± 1.1 vs. 10.3 ± 0.9 mcg/dL; P = 0.18). SGLT2i treatment has no effect on the CR hormone response to hypoglycemia in T1D. These data suggest that any reduction in hypoglycemia that occurs with these agents may be due to behavioral changes (e.g., lower insulin doses, less frequent bolusing), rather than a physiologic mechanism. Disclosure S. C. Boeder: Consultant; Self; Cecelia Health, Research Support; Self; Dexcom, Inc. D. G. Ines: None. E. R. Giovannetti: None. V. Hamidi: None. P. M. Burke: None. A. Armstrong: None. L. Carter: None. J. Pettus: Advisory Panel; Self; Novo Nordisk, Sanofi, Consultant; Self; Diasome Pharmaceuticals, Inc., Insulet Corporation, Lilly Diabetes, MannKind Corporation, Tandem Diabetes Care. Funding JDRF (2-SRA-2018-606-M-B)

Glucagon for hypoglycaemia treatment in type 1 diabetes.

To achieve strict glycaemic control and avoid chronic diabetes complications, individuals with type 1 diabetes (T1D) are recommended to follow an intensive insulin regimen. However, the risk and fear of hypoglycaemia often prevent individuals from achieving the treatment goals. Apart from early insulin suspension in insulin pump users, carbohydrate ingestion is the only option for preventing and treating non-severe hypoglycaemic events. These rescue treatments may give extra calories and cause overweight. As an alternative, the use of low-dose glucagon to counter hypoglycaemia has been proposed as a tool to raise glucose concentrations without adding extra calories. Previously, the commercially available glucagon formulations required reconstitution from powder to a solution before being injected subcutaneously or intramuscularly-making it practical only for treating severe hypoglycaemia. Several companies have developed more stable formulations that do not require the time-consuming reconstitution process before use. As well as treating severe hypoglycaemia, non-severe and impending hypoglycaemia can also be treated with lower doses of glucagon. Once available, low-dose glucagon can be either delivered manually, as an injection, or automatically, by an infusion pump. This review focuses on the role and perspectives of using glucagon to treat and prevent hypoglycaemia in T1D.

Switching to Degludec is Associated with Reduced Hypoglycaemia, Irrespective of Definition Used or Patient Characteristics: Secondary Analysis of the ReFLeCT Prospective, Observational Study

IntroductionHypoglycaemia is a common side effect of insulin therapy; low or high glycated haemoglobin (HbA1c) levels, history of hypoglycaemia or long diabetes duration are known modifiers of hypoglycaemia risk. In randomised clinical trials, lower rates of hypoglycaemia have been observed with the new-generation insulin analogue, long-acting insulin degludec, compared with other basal insulins.MethodsThe ReFLeCT study was a prospective observational study over 12 months. Patient-reported diary data on hypoglycaemia were collected from patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) who were switching from other basal insulins to insulin degludec (degludec) at their physician’s discretion in routine clinical care. Two secondary analyses were undertaken to investigate the change in number of hypoglycaemic events: a post hoc analysis using the updated American Diabetes Association (ADA) level 1, 2 and 3 hypoglycaemia definitions, and a pre-specified analysis using patient characteristics (baseline HbA1c, diabetes duration, and physician’s rationale for initiating degludec).ResultsSwitching to degludec was associated with significantly fewer hypoglycaemic events for all definitions in T1D, and level 1 and 2 in T2D (too few level 3 events for statistical comparison). Moreover, patient characteristics did not influence the observed reduction in hypoglycaemia in T1D and T2D.ConclusionThese results demonstrate that switching to degludec from other basal insulins was associated with reduced rates of hypoglycaemia, irrespective of the definition used or baseline patient characteristics.Trial RegistrationNCT02392117Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-020-00875-1) contains supplementary material, which is available to authorized users.

270-OR: Nocturnal Hypoglycemia with Insulin Degludec and Glargine U100 in Patients with Type 1 Diabetes Prone to Severe Nocturnal Hypoglycemia (HypoDeg): A CGM Substudy

Background and Aims: Nocturnal hypoglycemia is a major source of concern of people with type 1 diabetes (T1D) and may result in suboptimal glycemic control due to avoidance behavior. Optimal basal insulin therapy may reduce nocturnal hypoglycemia. Insulin degludec is associated with lower risk of nocturnal hypoglycemia in T1D. However, it has not been studied in people specifically prone to severe nocturnal hypoglycemia. We report frequencies of CGM-recorded nocturnal non-severe hypoglycemia (NSH) from the HypoDeg trial, which compared insulin degludec with insulin glargine in people with T1D and previous severe nocturnal hypoglycemia. Materials and Methods: Seventy-four people completed 4 x 6 days of blinded CGM (Medtronic iPro) during a 2-year randomized cross-over study. CGM traces were reviewed for clinically important hypoglycemic events ≤ 3.0 mmol/L according to current international consensus. Results: When defining night-time from 23-06:59 a total of 193 episodes of nocturnal NSH were found at the glucose threshold ≤ 3.0 mmol/L. A 53% (95% confidence interval [CI] 35%-64%; p&amp;lt;0.001) relative risk reduction (RRR) in nocturnal NSH during treatment with insulin degludec (0.6 episodes/person-week) was observed as compared to insulin glargine (1.3 episodes/person-week). The reduction in nocturnal NSH was mainly due to a 52% (95%[CI]:32-70%; p&amp;lt;0.001) RRR in nocturnal asymptomatic hypoglycemia with insulin degludec (0.4 episodes/person-week) as compared to insulin glargine (0.9 episodes/person-week). Similar results were found when defining night-time from 00-05:59. Conclusion: People with T1D prone to nocturnal severe hypoglycemia have lower rates of CGM-recorded nocturnal hypoglycemia with insulin degludec as compared to insulin glargine. Disclosure J.M. Brøsen: None. R.M. Agesen: Employee; Self; Novo Nordisk A/S. A. Alibegovic: Employee; Self; Novo Nordisk A/S. H.U. Andersen: Advisory Panel; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. P. Gustenhoff: Advisory Panel; Self; Abbott Laboratories, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi-Aventis. T.K. Hansen: None. T. Jensen: Stock/Shareholder; Self; Novo Nordisk A/S. C.B. Juhl: None. S. Lerche: None. K. Nørgaard: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic, Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc. H.D. Parving: None. L. Tarnow: None. B. Thorsteinsson: None. U. Pedersen-Bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S.

Value of Capillary Glucose Profiles in Assessing Risk of Nocturnal Hypoglycemia in Type1 Diabetes Based on Continuous Glucose Monitoring.

IntroductionThis study aimed to evaluate the occurrence of nocturnal hypoglycemia in type 1 diabetes (T1D) based on continuous glucose monitoring (CGM), and to explore the value of capillary glucose profiles in assessing the risk of nocturnal hypoglycemia. The study also intended to develop a predictive model to identify people with high risk of nocturnal hypoglycemia.MethodsA total of 169 participants with T1D received 3 days of blinded CGM; meanwhile, their self-monitoring blood glucose (SMBG) profiles were recorded. Logistic regression analyses were used to evaluate contributory factors of nocturnal hypoglycemia. Potential indicators were estimated using area under receiver operator curve (AUC) analyses.ResultsDuring the retrospective CGM period, 95 (56.2%) participants with T1D reported 238 events of hypoglycemia, and 69 (29.0%) of these episodes occurred during the nighttime. Increased risk of nocturnal hypoglycemia correlated with lower HbA1c, glycated albumin, and mean blood glucose (OR = 0.790, 0.940, 0.651, respectively; P < 0.05) and higher standard deviation, mean amplitude of glycemic excursions, and low blood glucose index (OR = 1.463, 1.168, 4.035, respectively; P < 0.05) after adjustment for age and duration. Of the daily SMBG profiles, fasting blood glucose (OR = 0.643, P = 0.001) and blood glucose at bedtime (OR = 0.851, P = 0.037) were associated with the occurrence of nocturnal hypoglycemia. The BGn model, which was derived from the variation of capillary glucose, could discriminate individuals with increased risk of nocturnal hypoglycemia (AUC = 0.774).ConclusionsNocturnal hypoglycemia constitutes nearly one-third of hypoglycemic events in people with T1D. Strict glycemic control and great fluctuation of glucose are potential contributory factors. Daily SMBG profiles and the BGn model could help assess the risk of nocturnal hypoglycemia in T1D, which may support further development of preventive strategies.

Glutamine and type 1 diabetes mellitus

Recent literature suggests dietary glutamine supplementation may lower blood glucose in patients with type 1 diabetes (T1D), who have no residual insulin secretion. The mechanisms and potential relevance to the care of T1D remain unclear. Glutamine is involved in multiple pathways including gluconeogenesis, lipolysis, antioxidant defense, the production of nitric oxide, the secretion of peptides (e.g., glucagon-like peptide 1, GLP-1), or neuromediators (e.g., [Latin Small Letter Gamma]-aminobutyric acid), all processes that may impact insulin sensitivity and/or glucose homeostasis. The article reviews potential mechanisms and literature evidence suggesting a role in improving glucose tolerance in patients with illness associated with insulin resistance, as well as the preliminary evidence for the increased incidence of postexercise hypoglycemia in T1D after oral glutamine. Further studies are warranted to determine whether the lowering effect of glutamine on blood glucose is sustained over time. If so, long-term randomized trials would be warranted to determine whether there is a role for glutamine as an adjunct dietary supplement to improve glucose control in patients with T1D.

Beliefs and Experiences of Fear of Hypoglycemia and Use of Uncooked Cornstarch before Bedtime in Persons with Type 1-Diabetes

Introduction: Among persons living with type 1-diabetes hypoglycemia and fear of hypoglycemia remain limiting barriers for achieving optimal glucose control and a good quality of life. Fear of hypoglycemia has been found stable over time if not treated. Uncooked cornstarch has been found to reduce the risk of hypoglycemia but has not been studied in relation to fear of hypoglycemia. The aims of this study were to through clinical data, self-reported measures and clinical interviews explore subjects’ experience of using uncooked cornstarch before bedtime and their beliefs and experiences of fear of hypoglycemia. Methods: Mixed methods with both quantitative and qualitative data were used. Self-reported measures of hypoglycemia and fear of hypoglycemia were compared to subjects’ responses during a clinical interview. The interviews were analyzed with a functional behavior analytical approach. Results: A total of five subjects took part in the study. One subject perceived the uncooked cornstarch helpful in reducing hypoglycemia. Several subjects could recall frightening hypoglycemic episodes triggering their fear. Three out of the five subjects reported avoidance behaviors such as excessive self-monitoring of blood glucose or overeating related to fear of hypoglycemia. Conclusions: The uncooked cornstarch was found appetizing but was not perceived as having an effect on BG or hypoglycemia frequency. The clinical interviews confirmed previous research regarding experience of hypoglycemia and fear of hypoglycemia.

Nrf2-Mediated Neuroprotection Against Recurrent Hypoglycemia Is Insufficient to Prevent Cognitive Impairment in a Rodent Model of Type 1 Diabetes.

It remains uncertain whether recurrent nonsevere hypoglycemia (Hypo) results in long-term cognitive impairment in type 1 diabetes (T1D). This study tested the hypothesis that specifically in the T1D state, Hypo leads to cognitive impairment via a pathological response to oxidative stress. Wild-type (Control) and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) null mice were studied. Eight groups of mice (Control and Nrf2(-/-) ± T1D and ± Hypo) were subject to recurrent, twice-weekly, insulin or saline injections over 4 weeks, after which cognitive function was assessed and brain tissue analyzed. Recurrent moderate hypoglycemia in T1D, but not Control, mice significantly impaired cognitive performance, and this was associated with hippocampal oxidative damage and inflammation despite an enhanced expression of Nrf2 and its target genes Hmox1 and Nqo1 In Nrf2(-/-) mice, both T1D and Hypo independently resulted in impaired cognitive performance, and this was associated with oxidative cell damage and marked inflammation. Together, these data suggest that Hypo induces an Nrf2-dependent antioxidant response in the hippocampus, which counteracts oxidative damage. However, in T1D, this neuroprotective mechanism is insufficient to prevent neuronal oxidative damage, resulting in chronic deficits in working and long-term memory.

Vitamin C Further Improves the Protective Effect of Glucagon-Like Peptide-1 on Acute Hypoglycemia-Induced Oxidative Stress, Inflammation, and Endothelial Dysfunction in Type 1 Diabetes

OBJECTIVETo test the hypothesis that acute hypoglycemia induces endothelial dysfunction and inflammation through the generation of an oxidative stress. Moreover, to test if the antioxidant vitamin C can further improve the protective effects of glucagon-like peptide 1 (GLP-1) on endothelial dysfunction and inflammation during hypoglycemia in type 1diabetes.RESEARCH DESIGN AND METHODSA total of 20 type 1 diabetic patients underwent four experiments: a period of 2 h of acute hypoglycemia with or without infusion of GLP-1 or vitamin C or both. At baseline, after 1 and 2 h, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2a (PGF2a), soluble intracellular adhesion molecule-1a (sICAM-1a), interleukin-6 (IL-6), and flow-mediated vasodilation were measured. At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced.RESULTSAt 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced.CONCLUSIONSThis study shows that vitamin C infusion, during induced acute hypoglycemia, reduces the generation of oxidative stress and inflammation, improving endothelial dysfunction, in type 1 diabetes. Furthermore, the data support a protective effect of GLP-1 during acute hypoglycemia, but also suggest the presence of an endothelial resistance to the action of GLP-1, reasonably mediated by oxidative stress.

Vildagliptin Reduces Glucagon during Hyperglycemia and Sustains Glucagon Counterregulation during Hypoglycemia in Type 1 Diabetes

The dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits glucagon secretion at hyperglycemia but appears to enhance glucagon counterregulation during hypoglycemia in type 2 diabetes. The objective of the investigation was to study whether vildagliptin also improves α-cell function in type 1 diabetes (T1D). The study was a single-center, double-blind, randomized, placebo-controlled crossover study involving 28 patients with C-peptide negative and antibody positive T1D [21 males, seven females, glycosylated hemoglobin 57.9 mmol/mol (7.5%)]. Patients received vildagliptin (50 mg twice a day) or placebo as an add-on to their insulin therapy for 4 wk each. On d 28 of the respective treatment period, patients were served a standard meal (500 kcal) to raise the circulating incretin hormone levels followed by a hyperinsulinemic hypoglycemic clamp at 2.5 mmol/liter. The increase in plasma glucagon levels during the 30-min hypoglycemic clamp (min 165-195 of the test) was measured. During the meal, glucagon levels were lower with vildagliptin than with placebo (120 min area under the curve(glucagon) 2.4±0.2 vs. 2.6±0.2 nmol/liter×minutes, P=0.022 for between group difference). In contrast, during hypoglycemia, the glucagon counterregulation was not reduced by vildagliptin (increase in glucagon 1.5±1.0 pmol/liter with vildagliptin vs. 1.7±0.8 pmol/liter with placebo, P=NS). In addition, the counterregulatory responses in epinephrine, norepinephrine, cortisol, and pancreatic polypeptide were not different between the treatments. During the 4-wk treatment period, vildagliptin reduced the mean glycosylated hemoglobin, whereas there was no change with placebo [between group difference was -3.4±1.0 mmol/mol (-0.32±0.09%; P=0.002)] from baseline of 57.9 mmol/mol (7.5%). Vildagliptin, although inhibiting glucagon secretion during hyperglycemia, does not compromise the glucagon counterregulatory response during hypoglycemia in T1D.

Recent Advances in the Prevention of Hypoglycemia in Type 1 Diabetes

Iatrogenic hypoglycemia is one of the chief barriers to optimal glycemic control in people with type 1 diabetes (T1D). As a common contributor to morbidity and mortality in T1D, severe hypoglycemia (SH) is also a major fear for people with T1D and their families. Consequently, fear of hypoglycemia and hypoglycemia-avoidant behaviors are predominant limiting factors in achieving euglycemia in people with T1D. Nocturnal SH and hypoglycemia unawareness are prevalent obstacles in the detection of hypoglycemia which further impair the prevention and treatment of SH. Various strategies and technologies have already been developed to help detect and prevent hypoglycemia, including improved patient education, frequent self-monitoring of blood glucose levels, the use of rapid-acting and basal insulin analogs, continuous subcutaneous insulin infusion therapy, exercise-related insulin modifications, and continuous glucose monitors. The efficacy of these methods is well established, but further advances are still needed. The purpose of this review is to describe these currently available methods and to emphasize recent progress related to the prevention of hypoglycemia in T1D.