Hypoglycemia Research Articles

Hypoglycemia in Type 2 Diabetes Patients Substituted with Insulin Degludec Aspart from Premixed Insulin Therapy: a Quasi Experimental Study

Hypoglycemia in Type 2 Diabetes Patients Substituted with Insulin Degludec Aspart from Premixed Insulin Therapy: a Quasi Experimental Study

Can prophylactic oral dextrose solution prevent hypoglycemia in high risk newborns?

Prophylactic oral dextrose gel recommended to prevent hypoglycaemia in high risk babies is not readily available and affordable. This study was therefore conducted to find out if oral dextrose solution decreases the incidence of hypoglycaemia in high risk neonates. This study included 186 high risk newborns. Oral 10% dextrose 2ml/kg was given at 30 minutes, 2, 6 and 12 hours of life, along with direct breastfeeding. Capillary blood glucose measurement was monitored at 2, 6, 12, 24, 48 and 72 hours of life. Low blood sugar levels were confirmed by simultaneous venous blood sampling. Statistical tests used were chi square for proportions and ANOVA for means. Of the 186 high risk babies maximum babies were small for gestational age (n = 68, 36.5%). Among the high risk babies, 7 (3.7%) developed hypoglycaemia. All were asymptomatic. A higher proportion of hypoglycaemia was seen IUGR babies (n = 2/9, 22.2%) and in those delivered by caesarean section (n =3/71, 4.2%). Compared to the incidence of hypoglycaemia (7.2%) in the historical control group the incidence of hypoglycaemia (3.7%) in interventional group was lower though statistically not significant (p=NS). There is a decrease in the incidence of hypoglycemia in high-risk infants given prophylactic oral dextrose solution. However, this trend was not statistically significant.

Frequency of hypoglycaemia with basal insulin treatments in adults with type 1 diabetes treated with basal-bolus insulin regimens in treat-to-target trials: A narrative review.

To summarise, in a narrative review, published data on hypoglycaemia occurrence with basal insulin therapy in adults with type 1 diabetes treated with basal-bolus insulin regimens in treat-to-target randomised controlled trials. Data were included from 21 eligible trials, which mainly used self-measured blood glucose or plasma glucose to detect hypoglycaemia. All-day self-measured blood glucose or plasma glucose level 2 (glucose threshold of 3.1 or 3.0 mmol/L) and level 3 (severe, requiring assistance) hypoglycaemic events were reported, respectively, by a range of 69.0%-97.5% and 0%-13.4% adults when receiving basal-bolus insulin therapy, with rates of 10.6-68.1 and 0.0-0.4 events per patient-year of exposure, respectively. Hypoglycaemia rates measured using continuous glucose monitoring (three studies) were numerically, yet consistently, higher than with either other method, except when limiting to symptomatic events. Nocturnal hypoglycaemia rates were generally less than 30% of the equivalent all-day rates. Differences across the studies in design (e.g., titration targets) and participant characteristics hindered comparison of hypoglycaemia rates by insulin formulation. Consequently, few trends were identified by insulin formulation, study methodology or individuals' characteristics, suggesting that further research is required to identify treatment strategies that facilitate development of individualised recommendations to lower hypoglycaemia risk. These findings are useful to understand hypoglycaemia risk with available basal insulin therapies when used in a multiple daily injection regimen, as well as to provide context for the results of ongoing and future clinical trials, including those for two once-weekly basal insulins, insulin icodec and basal insulin Fc.

Mechano-sensor Piezo1 inhibits glucagon production in pancreatic α-cells

ObjectiveGlucagon is a critical hormone regulating glucose metabolism. It stimulates the liver to release glucose under low blood sugar conditions, thereby maintaining blood glucose stability. Excessive glucagon secretion and hyperglycemia is observed in individuals with diabetes. Precise modulation of glucagon is significant to maintain glucose homeostasis. Piezo1 is a mechanosensitive ion channel capable of converting extracellular mechanical forces into intracellular signals, thus regulating hormonal synthesis and secretion. This study aims to investigate the role of Piezo1 in regulating glucagon production in α cells. MethodsThe effects of Piezo1 on glucagon production were examined in normal- or high-fat diet fed α cell-specific Piezo1 knockout mice (Gcg-Piezo1−/−), and the murine pancreatic α cell line αTC1–6. Expression of Proglucagon was investigated by real-time PCR and western blotting. Plasma glucagon and insulin were detected by enzyme immunoassay. ResultsUnder both normal- and high-fat diet conditions, Gcg-Piezo1−/− mice exhibited increased pancreatic α cell proportion, hyperglucagonemia, impaired glucose tolerance, and activated pancreatic mTORC1 signaling. Activation of Piezo1 by its agonist Yoda1 or overexpression of Piezo1 led to decreased glucagon synthesis and suppressed mTOR signaling pathway in αTC1–6 cells. Additionally, the levels of glucagon in the medium were also reduced. Conversely, knockdown of Piezo1 produced opposite effects. ConclusionOur study uncovers the regulatory role of the Piezo1 ion channel in α cells. Piezo1 influences glucagon production by affecting mTOR signaling pathway.

A self-powered and supercapacitive microneedle continuous glucose monitoring system with a wide range of glucose detection capabilities

Continuous detection of sudden changes in blood glucose is essential for individuals with diabetes who have difficulty in maintaining optimal control of their blood glucose levels. Hypoglycemic shock or a hyperglycemic crisis are likely to occurs in patients with diabetes and poses a significant threat to their lives. Currently, commercial continuous glucose monitoring (CGM) has limits in the glucose concentration detection range, which is 40–500 mg/dL, making it difficult to prevent the risk of hyperglycemic shock. In addition, current CGMs are invasive, cause pain and irritation during usage, and expensive. In this research, we overcome these limitations by introducing a novel mechanism to detect glucose concentration using supercapacitors. The developed CGM, which is self-powered and minimally invasive due to the use of microneedles, can detect a wider range of glucose concentrations than commercial sensors. In addition, efficacy and stability were proven through in vitro and in vivo experiments. Thus, this self-powered, microneedle and supercapacitive-type CGM can potentially prevent both hypoglycemic and complications of hyperglycemia without pain and with less power consumption than current commercial sensors.

Hypoglycemia during hyperosmolar hyperglycemic crises is associated with long-term mortality

BackgroundPrevious research has indicated that hypoglycemia during hospitalization is a predictor of unfavorable outcomes in patients with diabetes. However, no studies have examined the long-term impact of hypoglycemia in adults admitted for hyperglycemic crises. The study was aimed to investigate the long-term implications of hypoglycemia during hyperosmolar hyperglycemic crises, particularly in terms of all-cause mortality.MethodsThis retrospective cohort study included 170 patients (82 men [48.2%], median age 72 years) admitted to a university hospital for hyperosmolar hyperglycemic crises, including pure hyperosmolar hyperglycemic states and hyperosmolar diabetic ketoacidoses. We separately investigated the prognostic significance of hypoglycemia on mortality during the initial intravenous insulin therapy phase and during the later subcutaneous insulin therapy phase, both during hospitalization and in the long term (median follow-up, 652 days; range 2–3460 days).ResultsBoth hypoglycemia during the initial intravenous insulin therapy phase (observed in 26.5% of patients) and hypoglycemia during the later subcutaneous insulin therapy phase (observed in 52.7% of patients) were associated with long-term mortality. After adjusting for potential confounders, hypoglycemia during the initial intravenous insulin therapy phase remained associated with mortality (hazard ratio 2.10, 95% CI 1.27–3.46, p = 0.004).ConclusionsHypoglycemia during hyperosmolar hyperglycemic crises is a marker of long-term mortality, especially when it occurs during the initial intravenous insulin therapy phase.

A system that responds to low blood sugar

A system that responds to low blood sugar

Impact of hypoglycemia after gastrectomy on Global Leader Initiative on Malnutrition-defined malnutrition: a retrospective study.

The Global Leader Initiative on Malnutrition (GLIM) criteria were developed in 2018 as a global indicator of malnutrition, and the term 'malnutrition-sarcopenia syndrome' was established. Recently, it has been reported that fluctuations in blood glucose are related to sarcopenia. In this study, we investigated the effects of glucose fluctuations on malnutrition after gastrectomy using a continuous glucose monitoring (CGM) device. We analyzed the data of 69 patients with gastric cancer (GC) who underwent curative gastrectomy between November 2017 and December 2020. CGM was performed over a 2-week period at 1month and 1year after surgery. The GLIM criteria included weight loss, the body mass index (BMI), and the psoas muscle mass index (PMI). One year after surgery, 25 and 35 patients had severe and moderate malnutrition, respectively. The time below range (TBR) (percent of time the glucose concentration was < 70mg/dL) and nocturnal (00:00-06:00) TBR were significantly higher in the severe malnutrition group than in the other groups (TBR: normal/moderate 17.9% vs. severe 21.6%, P = 0.039, nocturnal TBR; normal/moderate 30.6% vs. severe 41.1%, P = 0.034). Post-gastrectomy hypoglycemia, including long nocturnal hypoglycemia, was higher in severely malnourished patients than in other patients even 1year after surgery. Prevention of nocturnal hypoglycemia may be the key to improving malnutrition following gastrectomy.

Efficacy and safety of basal insulins in people with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.

The comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear differentiation between different basal insulins as the optimal choice for initiation. A comprehensive search of MEDLINE, Embase, Cochrane Library, ISI, and Scopus, and a reference list of retrieved studies and reviews were performed up to November 2023. We identified phase III randomized controlled trials (RCTs) comparing the efficacy and safety of basal insulin regimens. The primary outcomes evaluated were HbA1c reduction, weight change, and hypoglycemic events. The revised Cochrane ROB-2 tool was used to assess the methodological quality of the included studies. A random-effects frequentist network meta-analysis was used to estimate the pooled weighted mean difference (WMD) and odds ratio (OR) with 95% confidence intervals considering the critical assumptions in the networks. The certainty of the evidence and confidence in the rankings was assessed using the GRADE minimally contextualized approach. Of 20,817 retrieved studies, 44 RCTs (23,699 participants) were eligible for inclusion in our network meta-analysis. We found no significant difference among various basal insulins (including Neutral Protamine Hagedorn (NPH), ILPS, insulin glargine, detemir, and degludec) in reducing HbA1c. Insulin glargine, 300 U/mL (IGlar-300) was significantly associated with less weight gain (mean difference ranged from 2.9 kg to 4.1 kg) compared to other basal insulins, namely thrice-weekly insulin degludec (IDeg-3TW), insulin degludec, 100 U/mL (IDeg-100), insulin degludec, 200 U/mL (IDeg-200), NPH, and insulin detemir (IDet), but with low to very low certainty regarding most comparisons. IDeg-100, IDeg-200, IDet, and IGlar-300 were associated with significantly lower odds of overall, nocturnal, and severe hypoglycemic events than NPH and insulin lispro protamine (ILPS) (moderate to high certainty evidence). NPH was associated with the highest odds of overall and nocturnal hypoglycemia compared to others. Network meta-analysis models were robust, and findings were consistent in sensitivity analyses. The efficacy of various basal insulin regimens is comparable. However, they have different safety profiles. IGlar-300 may be the best choice when weight gain is a concern. In contrast, IDeg-100, IDeg-200, IDet, and IGlar-300 may be preferred when hypoglycemia is the primary concern.

Prepartum behaviors as early indicators for postpartum energy associated biomarkers status in Holstein dairy cows.

Our main aim was to investigate the predictive value of prepartum behaviors such as total daily rumination (TDR), total daily activity (TDA) and dry matter intake (DMI) as early indicators to detect cows at risk for hyperketonemia (HYK), hypoglycemia (HYG) or high non-esterified fatty acid (NEFA) status in the first (wk1) and second week (wk2) postpartum. In a case control study, 64 Holstein cows were enrolled 3 weeks before the expected time of calving and monitored until 15 days in milk (DIM). Postpartum blood samples were taken at D3 and D6 for wk1 and at D12 and D15 for wk2 to measure beta-hydroxybutyrate, NEFA and glucose concentration. Ear-mounted accelerometers were used to measure TDR and TDA. DMI and milk yield were obtained from farm records. Relationships between the average daily rate of change in prepartum TDR (ΔTDR), TDA (ΔTDA), and DMI (ΔDMI) with postpartum HYK, HYG and NEFA status in wk1 and wk2 post-partum were evaluated using linear regression models. Models were adjusted for potential confounding variables, and covariates retained in the final models were determined by backward selection. No evidence was found to support the premise that prepartum ΔTDR, ΔTDA or ΔDMI predicted postpartum HYK, HYG or NEFA status in wk1 or in wk2. Overall, prepartum ΔTDR, ΔTDA and ΔDMI were not effective predictors of HYK, HYG or NEFA status in the first 2 weeks postpartum.

Spontaneous hypoglycemia: should we mind the gap? Long-term follow-up of healthy people who met Whipple’s triad criteria

ContextPatients discharged as “healthy” with the symptoms of spontaneous hypoglycemia, commonly known as Whipple’s triad, need more attention.ObjectiveCharacterization and long-term follow-up of symptom development in patients with spontaneous hypoglycemia discharged as “healthy”. The objective was to ascertain whether any conditions related to the symptoms were diagnosed during the follow-up period.MethodsRetrospective analysis of patient data and evaluation of a specific questionnaire on the development of symptoms of spontaneous hypoglycemia. In addition, patient questionnaires were evaluated and primary care physicians were asked about possible diseases not recorded at baseline that occurred during the follow-up period.SettingCenter for Endocrinology, Diabetology, and Osteology at the University Hospital Marburg, Inpatient Department, Germany.PatientsAll patients who presented to our center for the 72-hour fast between 2005 and 2018 and were discharged without an internal medicine diagnosis were included.InterventionsSurvey by questionnaire, via telephone interview.Main outcome measuresPatient-reported information on current symptoms compared to original symptoms, diagnosis of insulinoma or diabetes mellitus during follow-up, matched with primary care physician data, and metabolic and biometric data such as body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA IR), insulin sensitivity Matsuda Index (ISI-M), and area under the curve.ResultsA total of 41 datasets were evaluated at baseline and 38 patients were followed for an average of approximately 10 years. In total, 61% of respondents still reported the same symptoms as at baseline. No insulinoma was missed in these patients. Only two of the 38 patients developed diabetes mellitus.ConclusionThe high percentage of patients who are discharged as “healthy” and still have symptoms after many years is disturbing. It is possible that the symptoms are not due to low blood glucose. We urge caution with use of the term “healthy”. We advocate a multidisciplinary therapeutic approach after an organic cause of hypoglycemia has been ruled out. Psychosomatic treatment seems to be useful. In addition, more research should be conducted on this topic.

Effects of Switching from Degludec to Glargine U300 in Patients with Insulin-Dependent Type 1 Diabetes: A Retrospective Study.

Background and Objectives: Degludec (Deg) and glargine U300 (Gla-300) are insulin analogs with longer and smoother pharmacodynamic action than glargine U100 (Gla-100), a long-acting insulin that has been widely used for many years in type 1 and type 2 diabetes. Both improve glycemic variability (GV) and the frequency of hypoglycemia, unlike Gla-100. However, it is unclear which insulin analog affects GV and hypoglycemia better in patients with insulin-dependent type 1 diabetes. We evaluated the effects of switching from Deg to Gla-300 on the day-to-day GV and the frequency of hypoglycemia in patients with insulin-dependent type 1 diabetes treated with Deg-containing basal-bolus insulin therapy (BBT). Materials and Methods: We conducted a retrospective study on 24 patients with insulin-dependent type 1 diabetes whose treatment was switched from Deg-containing BBT to Gla-300-containing BBT. We evaluated the day-to-day GV measured as the standard deviation of fasting blood glucose levels (SD-FBG) calculated by the self-monitoring of blood glucose records, the frequency of hypoglycemia (total, severe, and nocturnal), and blood glucose levels measured as fasting plasma glucose (FPG) levels and hemoglobin A1c (HbA1c). Results: The characteristics of the patients included in the analysis with high SD-FBG had frequent hypoglycemic events, despite the use of Deg-containing BBT. For this population, SD-FBG and the frequency of nocturnal hypoglycemia decreased after the switch from Deg to Gla-300. Despite the decrease in the frequency of nocturnal hypoglycemia, the FPG and HbA1c did not worsen by the switch. The change in the SD-FBG had a negative correlation with the SD-FBG at baseline and a positive correlation with serum albumin levels. Conclusions: Switching from Deg to Gla-300 improved the SD-FBG and decreased the frequency of nocturnal hypoglycemia in insulin-dependent type 1 diabetes treated with Deg-containing BBT, especially in cases with low serum albumin levels and a high GV.

Facility capacity and provider knowledge for cholera surveillance and diarrhoea case management in cholera hotspots in the Democratic Republic of Congo – a mixed-methods study

ABSTRACT Background Wider healthcare-strengthening interventions are recommended in cholera hotspots and could benefit other types of diarrhoeal diseases which contribute to greater mortality than cholera. Objective Describe facility capacity and provider knowledge for case management of diarrhoea and cholera surveillance in cholera hotspots in the Democratic Republic of Congo (DRC) among health facilities, drug shops, and traditional health practitioners. Methods We conducted a sequential exploratory mixed-method study, using focus group discussions, facility audits, and provider knowledge questionnaires during September and October 2022 in North Kivu and Tanganyika provinces, Eastern DRC. Content analysis was used for qualitative data. Quantitative data were summarised by facility level and healthcare provider type. Audit and knowledge scores (range 0–100) were generated. Multivariable linear regression estimated association between scores and explanatory factors. Qualitative and quantitative data were triangulated during interpretation. Results Overall, 244 facilities and 308 providers were included. The mean audit score for health facilities was 51/100 (SD: 17). Private facilities had an −11.6 (95% CI, −16.7 to −6.6) lower adjusted mean score compared to public. Mean knowledge score was 59/100 (95% CI, 57 to 60) for health facility personnel, 46/100 (95% CI, 43 to 48) for drug shop vendors and 37/100 (95% CI, 34 to 39) for traditional health practitioners. Providers had particularly low knowledge concerning when to check for low blood sugar, use of nasogastric tubes, and dosing schedules. Knowledge about case definitions for cholera was similar between groups (range 41–58%) except for traditional health practitioners for the definition during an outbreak 15/73 (21%). Conclusions Increasing awareness of cholera case definitions in this context could help improve cholera surveillance and control. Increased support and supervision, especially for private providers, could help ensure facilities are equipped to provide safe care. More nuanced aspects of case management should be emphasised in provider training.

Continuous Glucose Monitoring Profiles and Health Outcomes after Dapagliflozin Plus Saxagliptin vs Insulin Glargine.

Glycemic variability and hypoglycemia during diabetes treatment may impact therapeutic effectiveness and safety, even when glycated hemoglobin (HbA1c) reduction is comparable between therapies. We employed masked continuous glucose monitoring (CGM) during a randomized trial of dapagliflozin plus saxagliptin (DAPA+SAXA) vs insulin glargine (INS) to compare glucose variability and patient-reported outcomes (PROs). 24-week sub-study of a randomized, open-label, two-arm, parallel-group, phase 3b study. Multicenter study (112 centers in 11 countries). 283 adults with type 2 diabetes (T2D) inadequately controlled with metformin ± sulfonylurea. DAPA+SAXA vs INS. Changes in CGM profiles, HbA1c, and PROs. Changes from baseline in HbA1c with DAPA+SAXA were similar to those observed with INS, with mean difference [95% CI] between decreases of -0.12% [-0.37 to 0.12%], P = .33. CGM analytics were more favorable for DAPA+SAXA, including greater percent time in range (> 3.9 and ≤ 10 mmol/L; 34.3 ± 1.9 vs 28.5 ± 1.9%, P = .033), lower percent time with nocturnal hypoglycemia (area under the curve ≤ 3.9 mmol/L; 0.6 ± 0.5 vs 2.7 ± 0.5%, P = .007), and smaller mean amplitude of glycemic excursions (-0.7 ± 0.1 vs -0.3 ± 0.1 mmol/L, P = .017). Improvements in CGM were associated with greater satisfaction, better body weight image, less weight interference, and improved mental and emotional well-being. DAPA+SAXA and INS were equally effective in reducing HbA1c at 24 weeks, but people with T2D treated with DAPA+SAXA achieved greater time in range, greater reductions in glycemic excursions and variability, less time with hypoglycemia, and improved patient-reported health outcomes.

Schmidt's Syndrome: An Uncommon Cause of Spontaneous Hypoglycemia

AbstractSchmidt's syndrome, or autoimmune polyendocrine syndrome type 2 (APS-2), is an uncommon disorder characterized by the co-occurrence of autoimmune thyroiditis and adrenalitis. APS-2 is defined as a combination of Addison's disease, autoimmune thyroid disease, and/or type 1 diabetes mellitus. It is an autosomal dominantly inherited polygenic disorder with incomplete penetrance; the candidate genes include but are not limited to HLA-DR3, HLA-DR4, CTLA-4, PTPN22, and CD25-IL-2. Autoimmune thyroiditis, often Hashimoto's disease, results in hypothyroidism. Primary adrenal failure results in enhanced secretion of adrenocorticotrophic hormone melanocyte and co-secretion of melanocyte-stimulating hormone, contributing to hyperpigmentation. Mineralocorticoid deficiency results in salt wasting, fatigue and cramps, postural hypotension, and hyperkalemia. Cortisol, an insulin counter-regulatory hormone, plays a pivotal role in maintaining euglycemia; deficiency predisposes to the development of hypoglycemia. We here report a rare presentation of Schmidt's syndrome as hypoinsulinemic hypoglycemia in a middle-aged male patient. Management includes treatment of acute hypoglycemic episodes with glucose or glucagon, long-term glucocorticoids and mineralocorticoids for adrenal insufficiency, and thyroid hormone supplements for hypothyroidism. This case report and brief overview aim to contribute to the scientific understanding of Schmidt's syndrome/APS-2. Additionally, here we briefly outline the diagnostic challenges in hypoglycemia evaluation, including the utilization of Whipple's triad and the gold standard supervised 72-hour fast and evaluation for primary adrenal and thyroid insufficiencies.

Synthesis and Hypoglycemic Effect of Insulin from the Venom of Sea Anemone Exaiptasia diaphana.

Sea anemone venom, abundant in protein and peptide toxins, serves primarily for predatory defense and competition. This study delves into the insulin-like peptides (ILPs) present in sea anemones, particularly focusing on their role in potentially inducing hypoglycemic shock in prey. We identified five distinct ILPs in Exaiptasia diaphana, exhibiting varied sequences. Among these, ILP-Ap04 was successfully synthesized using solid phase peptide synthesis (SPPS) to evaluate its hypoglycemic activity. When tested in zebrafish, ILP-Ap04 significantly reduced blood glucose levels in a model of diabetes induced by streptozotocin (STZ) and glucose, concurrently affecting the normal locomotor behavior of zebrafish larvae. Furthermore, molecular docking studies revealed ILP-Ap04's unique interaction with the human insulin receptor, characterized by a detailed hydrogen-bonding network, which supports a unique mechanism for its hypoglycemic effects. Our findings suggest that sea anemones have evolved sophisticated strategies to activate insulin receptors in vertebrates, providing innovative insights into the design of novel drugs for the treatment of diabetes.

Glycemic Management Around Postprandial Exercise in People With Type 1 Diabetes: Challenge Accepted.

The precise glycemic impact and clinical relevance of postprandial exercise in type 1 diabetes (T1D) has not been clarified yet. This work aimed to examine acute, subacute, and late effects of postprandial exercise on blood glucose (BG). A randomized, controlled trial comprised 4 laboratory visits, with 24-hour follow-up at home. Participants included adults with T1D (n = 8), aged 44 ± 13 years, with body mass index of 24 ± 2.1. Intervention included 30 minutes of rest (CONTROL), walking (WALK), moderate-intensity (MOD), or intermittent high-intensity (IHE) exercise performed 60 minutes after a standardized meal. Main outcome measures included BG change during exercise/control (acute), and secondary outcomes included the subacute (≤2 h after) and late glycemic effects (≤24 h after). Exercise reduced postprandial glucose (PPG) excursion compared to CONTROL, with a consistent BG decline in all patients for all modalities (mean declines -45 ± 24, -71 ± 39, and -35 ± 21 mg/dL, during WALK, MOD, and IHE, respectively (P < .001). For this decline, clinical superiority was demonstrated separately for each exercise modality vs CONTROL. Noninferiority of WALK vs MOD was not demonstrated, noninferiority of WALK vs IHE was demonstrated, and equivalence of IHE vs MOD was not demonstrated. Hypoglycemia did not occur during exercise. BG increased in the hour after exercise (more than after CONTROL; P < .001). More than half of participants showed hyperglycemia after exercise necessitating insulin correction. There were more nocturnal hypoglycemic events after exercise vs CONTROL (P < .05). Postprandial exercise of all modalities is effective, safe, and feasible if necessary precautions are taken (ie, prandial insulin reductions), as exercise lowered maximal PPG excursion and caused a consistent and clinically relevant BG decline during exercise while there was no hypoglycemia during or shortly after exercise. However, there seem to be 2 remaining challenges: subacute postexercise hyperglycemia and nocturnal hypoglycemia.

Nocturnal hypoglycemia is associated with next day cognitive performance in adults with type 1 diabetes: Pilot data from the GluCog study

Objective: Individuals with type 1 diabetes (T1D) have increased risk for cognitive dysfunction and high rates of sleep disturbance. Despite associations between glycemia and cognitive performance using cross-sectional and experimental methods few studies have evaluated this relationship in a naturalistic setting, or the impact of nocturnal versus daytime hypoglycemia. Ecological Momentary Assessment (EMA) may provide insight into the dynamic associations between cognition, affective, and physiological states. The current study couples EMA data with continuous glucose monitoring (CGM) to examine the within-person impact of nocturnal glycemia on next day cognitive performance in adults with T1D. Due to high rates of sleep disturbance and emotional distress in people with T1D, the potential impacts of sleep characteristics and negative affect were also evaluated. Methods: This pilot study utilized EMA in 18 adults with T1D to examine the impact of glycemic excursions, measured using CGM, on cognitive performance, measured via mobile cognitive assessment using the TestMyBrain platform. Multilevel modeling was used to test the within-person effects of nocturnal hypoglycemia and hyperglycemia on next day cognition. Results: Results indicated that increases in nocturnal hypoglycemia were associated with slower next day processing speed. This association was not significantly attenuated by negative affect, sleepiness, or sleep quality. Conclusions: These results, while preliminary due to small sample size, showcase the power of intensive longitudinal designs using ambulatory cognitive assessment to uncover novel determinants of cognitive fluctuation in real world settings, an approach that may be utilized in other populations. Findings suggest reducing nocturnal hypoglycemia may improve cognition in adults with T1D.

Impact of Lowered Inpatient Correctional Bedtime Insulin Dosing on Glycemic Outcomes of Veterans

Purpose: This study evaluated glycemic outcomes for hospitalized patients after reduction in bedtime correctional insulin dosing. Methods: This was a retrospective, single-center analysis of a protocol change that reduced bedtime correctional insulin scale. Comparable cohorts pre- and post-protocol change were created which included patients who were ordered correctional insulin with at least 1 blood glucose (BG) reading. The primary outcome was number of nocturnal hypoglycemia readings. Secondary outcomes included, but were not limited to, mean fasting BG, BG within various ranges, and length of stay. Results: 3 percent of patients in the post-protocol change group (N = 100) experienced nocturnal hypoglycemia compared to 6% of patients in the pre-change group (N = 100) (P = .507). There were no significant differences in BG ranges <110 mg/dL, <140 mg/dL, 140 to 180 mg/dL, and >180 mg/dL. However, 19% of patients in the post-protocol change group had BG of >250 mg/dL as compared to 9% in the pre-change group (P = .033). Mean fasting BG was higher in the post-protocol change group compared to the pre-change group (156.5 mg/dL vs 139.3 mg/dL [P = .002]), as was hospital length of stay (5.17 vs 4.6 days, [P = .024]). Conclusions: A decreased bedtime correctional insulin scale had mixed results with more patients achieving goal fasting BG but also more patients experiencing BG > 250 mg/dL and longer length of stay. Larger prospective studies are required to evaluate the safety and efficacy of this type of intervention and its long-term impact.

Efficacy and safety of insulin glargine 300 units/mL vs insulin degludec in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis.

Ultra-long-acting insulin analogs [insulin degludec (IDeg) and insulin glargine 300 units/mL (IGla-300)] offer a longer duration of action with less risk of hypoglycemia compared to other long-acting insulins. However, data about the comparative efficacy and safety are inconsistent. We searched CENTRAL, PubMed, Embase, ICTRP Search Portal, and ClinicalTrials.gov on 7 October 2022. Randomized controlled trials (RCTs) comparing the safety and efficacy of IDeg (100 or 200 units/mL) and IGla-300 in patients with type 1 or type 2 diabetes were included. Three review authors independently selected trials, assessed the risk of bias, extracted data, and evaluated the overall certainty of the evidence using GRADE. The primary outcomes were the change in glycated hemoglobin (HbA1c) and any hypoglycemia; the secondary outcomes were the change in fasting plasma glucose (FPG) and severe and nocturnal hypoglycemia. Four open-label RCTs were included (2727 participants), 3 parallel and 1 cross-over. Overall, the risk of bias assessment yielded some concern or high risk. There was a comparable change in HbA1c from baseline to the end of treatment, a mean difference of 0.07% (95% confidence interval (CI) 0.06 - 0.19; p = 0.29; 3 trials; 2652 patients; very low-certainty evidence), and a comparable rate of any hypoglycemia, rate ratio 1.02 (95% CI 0.8 - 1.3; p = 0.87; 3 trials; 2881 patients; very low-certainty evidence). IDeg resulted in more reduction in FPG compared to IGla-300, mean difference of 10.27 mg/dL (95% CI 7.25 - 13.29; p < 0.001; 3 trials; 2668 patients; low-certainty evidence). Similar rates of nocturnal and severe hypoglycemia were observed, rate ratio of 1.13 (95% CI 0.72 - 1.78; p = 0.54; 3 trials; 2668 patients; very low-certainty evidence) and 1.4 (95% CI 0.41 - 4.73; p = 0.59; 2 trials; 1952 patients; very low-certainty evidence), respectively. There is no evidence of a difference between IDeg and IGla-300 in the mean change in HbA1c and the risk of anytime, nocturnal, and severe hypoglycemia. IDeg appeared to cause a higher reduction in FPG compared to IGla-300. However, this finding should be interpreted with caution due to the small number of trials included and their high risk of bias. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022364891, identifier CRD42022364891.