Episodes Of Symptomatic Hypoglycemia Research Articles

Efficacy and Safety of Oral Semaglutide in the Treatment of Type 2 Diabetes: A Meta-Analysis.

This study aims to systematically review the efficacy and safety of oral semaglutide in the treatment of type 2 diabetes mellitus (T2DM) and provide a basis for the rational use of the drug in clinical practice. From the database's inception until February 2023, a systematic search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and China Science and Technology Journal Database to identify randomized controlled trials (RCTs) comparing the efficacy of oral semaglutide at dosages of 3, 7, and 14 mg (trial group) against placebo or other positive control drugs (control group) for the treatment of T2DM. Following literature screening and data extraction, the bias risk assessment tool in the Cochrane reviewer handbook 5.1.0 was used to evaluate the literature quality. Meta-analysis was carried out with RevMan 5.4 software. A total of 10 RCTs with 9541 patients were included. The meta-analysis results revealed that compared with placebo or positive control drugs (empagliflozin, sitagliptin, liraglutide, and dulaglutide), oral semaglutide significantly reduced the hemoglobin A1c (HbA1c) in patients (compared to placebo, 3 mg [MD = -0.61%, 95% CI (-0.89, -0.34)], 7 mg [MD = -1.12%, 95% CI (-1.45, -0.79)], 14 mg [MD = -1.08%, 95% CI (-1.32, -0.85)]; compared to positive control drugs (7 mg [MD = -0.26%, 95% CI (-0.38, -0.15)], 14 mg [MD = -0.37%, 95% CI (-0.52, -0.23)]). Oral semaglutide also showed certain advantages over placebo or positive control drugs in terms of weight loss, HbA1c reduction achievement rate, fasting plasma glucose level, and body mass index with overall dose-dependent efficacy. The incidence of nausea, diarrhea, and vomiting caused by oral semaglutide was higher than that of the placebo or positive control drugs, and the incidence of appetite decrease or constipation was higher than that of the placebo. Severe or symptomatic hypoglycemic episodes were reduced compared to positive control drugs. Oral semaglutide has definite clinical benefits of reducing blood glucose, body weight, reducing the risk of hypoglycemia, and with good safety.

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

Continuous moderate and intermittent high-intensity exercise in youth with type 1 diabetes: Which protection for dysglycemia?

AimFrom an early age, exercise is key to managing type 1 diabetes (T1D). However, hypoglycemia around aerobic exercise is a major barrier to physical activity in children. We explore whether intermittent high-intensity aerobic exercise (IHE), designed to mimic spontaneous childhood physical activity patterns, offers better protection against glycemic drop than continuous moderate-intensity exercise (CME). MethodsFive boys and 7 girls with T1D (9.8 ± 1.4y) performed ergo cycle-based randomized CME and IHE of identical duration and total mechanical load [50 %PWC170vs. 15sec(150 %PWC170)/30 sec passive recovery; both during two 10-min sets, 5 min in-between]. Capillary glycemia during exercise and interstitial glucose during recovery were compared between exercises and an inactive condition, controlling for baseline glycemia, carbohydrate and insulin. ResultsThe exercise-induced decrease in capillary glycemia was attenuated by 1.47 mmol·L−1 for IHE vs. CME (P < 0.05). No symptomatic hypoglycemic episodes occurred during exercises. Post-exercise time in hypoglycemia did not differ between conditions. During early recovery, CME reduced time spent > 16.7 mmol·L−1 compared with inactive days (P < 0.05; CME: 0 %; IHE: 16,7 %; INACTIVE: 41,7 %). ConclusionIHE appeared to limit the glycemic drop compared to CME. Performing 20-min CME or IHE was not associated with increased hypoglycemic risk compared to being inactive. CME appeared even transiently protective against serious hyperglycemia.

Influence of Anaerobic Exercise in Type 1 Diabetes Mellitus Biomarkers: ASystematic Review.

Physical exercise is part of the type 1 diabetes mellitus (T1DM) treatment. However, this practice is still neglected due to the wide variety of glycemic responses under the influence of anaerobic exercise. Therefore, this study aimed to investigate the influence of anaerobic exercise on biomarkers of T1DM. The systematic review was conducted on PubMed, Lilacs, and Embase, according to PRISMA. For this purpose, three groups of descriptors were used: Adults with T1DM, anaerobic physical exercise, and glycemic control. The search filter was set to human beings older than 18 years of age, longitudinal and cross-sectional studies, with studies published from 2000 to 2023 in English, Spanish, or Portuguese. Titles and abstracts were read independently by two reviewers, and then the articles were selected for this review. The Kappa coefficient was measured to evaluate the selection. A total of 738 articles were identified, and five were selected to be part of the review after applying the steps of the procedure. Some benefits were observed in fatigue reduction, absence of diabetic ketoacidosis requiring hospitalization, and enhancement of glucose monitoring during exercise. In the anaerobic workouts of the groups with T1DM, glycemic mean values ranged from 124.5-185.0 mg/dl, and glycated hemoglobin records ranged from 6.7-8.1%. Anaerobic exercise improved the biomarkers of T1DM, especially glycemic control, and the reduction of symptomatic hypoglycemic episodes. Anaerobic exercise can be performed by individuals with T1DM, suggesting an individualized training prescription and encouraging its practice associated with aerobic exercise.

THU370 A Case Of Ketosis-prone Diabetes In A Caucasian Man

Abstract Disclosure: Z. Saeed: None. C. Labib: None. M. Trabulsi: None. M. Varatharajah: None. Introduction: Ketosis-prone diabetes (KPD) also known as Flatbush diabetes, atypical diabetes and type 1.5 diabetes was first reported in the 1990s in African Americans in the Flatbush neighborhood of Brooklyn, New York. Its exact incidence is still unknown; however, it predominantly affects African American and Hispanic population and is less prevalent in Asians and Caucasians. It presents as diabetic ketoacidosis, a hyperglycemic emergency, in patients with no prior history of diabetes. In addition, it is usually seen in middle-aged, obese patients with a strong family history of Type 2 diabetes mellitus. Here we briefly describe the case of a lean 62-year-old man who presented to the hospital with HHS/DKA and was diagnosed with ketosis-prone diabetes. Case Presentation: 62-year-old man (BMI 21.37 Index) with a past medical history of alcoholic cirrhosis, Crohn’s disease and no personal or family history of diabetes presented to the hospital with complaint of nausea, polyuria and polydipsia. He was found to have hyperosmolar hyperglycemic state with diabetic ketoacidosis. He had a blood glucose of 833 mg/dL (70-110 mg/dL), anion gap of 14, sodium 111 mmol/L (136-145 mmol/L), potassium 7.0 mmol/L (3.5-5.1 mmol/L), creatinine 5.7mg/dL (0.6-1.3 mg/dL), pH 7.26 L (7.35-7.45 pH units), bicarbonate 16 mmol/L (22-34 mmol/L). He was started on an Insulin drip and later transitioned to subcutaneous long and short acting insulin after closure of anion gap. His Hemoglobin A1c was found to be 12.8% (4.8-6.1% A1C, Cpeptide 4.32 ng/mL (0.48-5.05 ng/mL), GAD65 antibody was negative. Four months prior to his hospital admission, his Hemoglobin A1C was 4.9%. Patient was discharged from the hospital on Insulin NPH/Regular 70/30 twice a day and sliding scale with meals. He was followed outpatient in clinic. Within a month of discharge he began to have episodes of symptomatic hypoglycemia, lowest recorded blood sugar was 49. His Insulin NPH/Regular was gradually tapered; he did not require the sliding scale at all. Four months after the episode of HHS/DKA, his repeat hemoglobin A1C was 5.7%. Case Discussion: Despite being known for around three decades now, the exact mechanism of ketosis prone diabetes is still poorly understood. It is thought to be due to insulin resistance as well as severe deficits in insulin secretion. It is classified further based on beta cell function and autoimmunity. In patients with preserved beta cell function and absence of autoimmunity, like our patient, with aggressive management insulin can eventually be discontinued. However, these patients remain at risk of developing diabetes later in life. Our case aims to shed light on the ubiquity of this disease so that physicians can diagnose it promptly and treat accordingly. Presentation: Thursday, June 15, 2023

Laron syndrome in South Indian children – A descriptive study

Objectives: The objectives of this study were to describe the clinical and biochemical features of five children with Laron syndrome (LS) from South India. Material and Methods: This is a prospective descriptive case series of five children with clinical and biochemical features of LS managed over 5 years. Results: Five children (two girls and three boys) with LS with the mean age group of 5.9 ± 1.7 years and the mean age at diagnosis of 2.7 ± 0.8 years are described. All children were born out of consanguinity and all had typical phenotypic facies of LS. The mean Z-scores of height, weight, and body mass index on follow-up for the cohort were −7.0 ± 1.6, −5.9 ± 2.8, and −0.1 ± 0.7, respectively, and they were within ± 2 SD of the mean for children in LS chart. The median basal growth hormone level for age was 13 ng/mL and the median growth hormone levels at 30 min, 60 min, 90 min, and 120 min post-stimulation test were 35 ng/mL, 35 ng/mL, 44 ng/mL, and 50 ng/mL, respectively. All of them had insulin-like growth factor-1 (IGF-1) levels less than the 3rd percentile and no increment during the IGF-1 generation test. The prevalence of micropenis was 100% and one child had symptomatic hypoglycemic episodes. Genetic analysis was performed in two boys and both harbored variants in the growth hormone receptor gene. Conclusion: LS should be suspected in children with clinical features of growth hormone deficiency along with elevated growth hormone levels and low IGF-1 levels with no increment of IGF-1 in the IGF-1 generation test.

Hypoglycemia in Patients With LAMA2-CMD

BackgroundHypoglycemia has been reported in patients with LAMA2-CMD, but the frequency, risk factors, and correlation to genotype/phenotype have not been systematically assessed to date. MethodsA retrospective cohort study was performed on 48 patients with LAMA2-CMD. Patients were divided into two groups: a hypoglycemic group, with at least one episode of hypoglycemia, and a nonhypoglycemic group. The groups were compared according to gait function, epilepsy, intellectual disability, constipation, gastroesophageal reflux, gastrostomy, weight percentile, scoliosis, the use of a ventilator device, the use of a feeding device, neuromuscular disease swallowing status scale, and type of mutation. ResultsFifteen patients (31.2%) presented with at least one episode of symptomatic hypoglycemia and eight (16.6% of the cohort) had two or more episodes. All patients who had hypoglycemia were in the nonambulant group. We observed a correlation between gait, the use of ventilator and feeding devices, and swallow function with hypoglycemia. Patients with extremely low weight were five times more likely to have recurrent episodes of hypoglycemia. The presence of at least one missense variant appears to be associated with a lower risk of hypoglycemia. ConclusionPatients with LAMA2-CMD are at risk of hypoglycemia. The risk is more relevant in patients with severe phenotype and patients with loss-of-function variants. For patients with extremely low weight, the risk is higher. Blood glucose should be actively measured in patients who are fasting or have infections, and health care providers should be prepared to identify and treat these patients.

A sub-analysis of the SAGE study in Italy indicates good glycemic control in type 1 diabetes

Background and aimsIntensive glycemic control minimizes the risk of micro- and macrovascular complications in patients with type 1 diabetes (T1D). We report glycemic control in Italian participants (age groups: 26–44, 45–64, and ≥65 years) of the global SAGE study. Methods and resultsThe primary endpoint was proportion of participants who achieved an HbA1c <7% in predefined age groups. In the 523 patients with T1D, mean age was 44.6 years and mean body mass index (BMI) was 25 kg/m2. Mean HbA1c was 7.5% and 29.4% had HbA1c <7.0%, with the highest percentage in those 26–45 years (31.7%) and the lowest in those ≥65 years (20%). Altogether, 22.9% of patients achieved their physician-established individualized HbA1c target. Most patients had ≥1 symptomatic hypoglycemic episode in the previous 3 months (≤70 mg/dL 82.5%; ≤54 mg/dL 61%). Severe hypo- and hyperglycemia were experienced by 16.3% and 12% of patients, of which 7.1 and 9.5%, respectively, required hospitalization/emergency visits. More patients achieved HbA1c <7% with CSII (30%) than with multiple daily insulin injections (27.9%). In multivariate analysis, BMI (OR 0.94, 95% CI 0.89–0.99, p = 0.032) and adherence to diet (OR 0.36, 95% CI 0.18–0.70, p = 0.0028) were significantly associated with HbA1c <7.0%. ConclusionsGlycemic control can be considered good in the Italian SAGE cohort, especially in younger patients, who more frequently use pumps/continuous glucose monitoring. Greater patient education and use of technology may further support this achievement. Patients should be encouraged to maintain a low BMI and adhere to their diet.

ODP219 Laparoscopic Gastrostomy tube (LGT) Placement for Management of Post Bariatric Surgery Hypoglycemia Syndrome (PBSHS).

Abstract Introduction Bariatric surgery is currently the most effective long term management for morbid obesity. Laparoscopic bariatric surgery whether gastric banding (LGB), sleeve gastrectomy (LSG) or gastric bypass (LRYGB) are now more commonly done. One major complication that can follow these procedures are the hypoglycemic syndromes; post bariatric surgery hypoglycemia syndrome (PBSHS). PBSHS is a spectrum ranging from mild reactive hypoglycemia to hypoglycemia with dumping syndrome to the most severe being post bariatric surgery nesidioblastosis (PBSN). Clinical case; The patient is a 33 yr old Caucasian lady with past history of morbid obesity who had LSG in 2012 with poor weight loss response. This was converted to LRYGB in 2016 with much better weight loss response. Within 1.5 yrs of the LRYGB however she started having recurrent hypoglycemic episodes which were initially mild and mostly postprandial (PP) but rapidly escalated to both fasting and PP states. Work up revealed that she had both reactive and fasting hypoglycemia and despite dietary interventions the episodes escalated and with "defensive eating" she progressively gained weight. Her hypoglycemic spells were confirmed as insulin mediated and consistent with PBSN. Medical therapy escalated to maximum dose acarbose, octreotide and high dose diazoxide. The frequency and severity of the hypoglycemic spells worsened and in 2021 she had over 7 hospital admissions from severe hypoglycemia with additional ED visits despite medication use including emergent glucagon use and CGMS monitoring with a DEXCOM device. She had hypoglycemia unawareness with progressively declining quality of life. Rather than possible attempted reversal of the LRYGB a LGT was placed to see if this would ameliorate her symptoms. She now drinks only non-caloric fluids per oral and all caloric intake is via the LGT. The clinical response has been swift and dramatic. Since LGT placement over 3 mths now she has had no symptomatic hypoglycemic episode and no ED nor hospital admissions. Post LGT placement CGMS profile demonstrated marked improvements in glycemic profile and post LGT mixed meal tests (MMT). A dichotomy was demonstrated between her glycemic profile on MMT for oral vs LGT caloric intake providing confirmation of the therapeutic effect of the LGT placement. Discussion With the increasing utilization of bariatric surgery for management of obesity and diabetes, the prevalence of PBSHS is expected to increase. This complication can be difficult and expensive to manage while negatively impacting weight loss and quality of life. Our case provides proof of principle evidence to suggest LGT placement as a management consideration in severe cases of PBSN. Conclusions LGT placement should be considered as an option in patients with severe PBSN that is poorly controlled with maximal medical and lifestyle interventions. Presentation: No date and time listed

PSUN254 Hirata's Disease - An Unexpected Surprise

Abstract The diagnosis of hypoglycemia in adults without diabetes mellitus is a medical challenge. Insulin autoimmune syndrome (IAS), also known as Hirata's Disease, is a rare condition characterized by episodes of spontaneous hypoglycemia secondary to hyperinsulinemia in the setting of positive insulin autoantibodies. 380 cases of IAS have been reported worldwide between 1970 and 2009 with majority of cases seen in patients of Asian descent. Here we present a case of a patient who presented with episodes of recurrent hypoglycemia secondary to IAS.85 year old Asian female presented to the endocrinology office for recurrent episodes of presyncope which were associated with presumed hypoglycemia. Patient denied a history of gastric bypass surgery, diabetes, use of oral hypoglycemic agents, change in eating habits, fevers, weight loss, or night sweats. A continuous glucose monitor was placed during the visit due to patient having difficulties using a glucometer and on follow-up, multiple episodes of hypoglycemia were noted, dropping down to 50mg/dL throughout the day. Due to recurrent symptomatic hypoglycemic episodes, she was admitted to the hospital for a workup. Point of care (POC) glucose on presentation to the ED was 166 mg/dL. 4 hours later in the ED, POC glucose was 42 mg/dL with serum confirmation of 44 mg/dL. Last meal was about 6 hours prior to this event and no dextrose containing solutions were used in the ER. Prior to correction of hypoglycemia, blood specimen sent for the following: c-peptide 3.4 ng/mL, beta-hydroxybutyrate 0.12 mmol/L, insulin level 285 µIU/mL, and proinsulin 93.7 pmol/L. Sulfonylurea screen was negative. CT pancreas with IV contrast showed no evidence of pancreatic mass suggestive of insulinoma. Due to recurrent episodes of hypoglycemia in the hospital, the patient was started on Diazoxide 50 mg every eight hours. An insulin antibody level sent from the initial specimen, eventually resulted and was elevated to above 50 U/mL. A comprehensive review of the patient's medications was performed; none were new or were associated with autoantibody formation. Patient denied recent symptoms of viral illness or family history of hypoglycemia. Literature review revealed the possible benefits of acarbose over diazoxide in management of IAS; diazoxide was switched to acarbose 50 mg three times a day before meals. Outpatient follow-up showed drastic reduced frequency of hypoglycemia while on Acarbose.IAS is a rare but important etiology of hypoglycemia in adults without diabetes mellitus. IAS involves the formation of insulin autoantibody complexes, which binds to the insulin receptors and prevents insulin from binding to its receptors in the postprandial phase. Insulin is then released from the complexes irrespective of blood glucose concentrations, therefore inducing postprandial hypoglycemia. Prompt recognition and diagnosis of IAS can allow for appropriate treatment and avoidance of performing unnecessary imaging and invasive procedures. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Efficacy and safety of combination of empagliflozin and metformin with combination of sitagliptin and metformin during Ramadan: an observational study

BackgroundManagement of diabetes during fasting is a clinical challenge. Sodium glucose co-transporter -2 inhibitors (SGLT2i) are considered safe with a low risk of hypoglycemia. However, studies on SGLT2i are scarce. This study was designed to compare the efficacy, safety, and tolerability of empagliflozin with metformin during Ramadan in comparison with sitagliptin and metformin.MethodsIt was a prospective, observational study, conducted at 11 different sites all across Pakistan on an outpatient basis during Ramadan (May 2021–June 2021). including 132 patients, 88 who received metformin and sitagliptin, and 44 patients who received metformin and empagliflozin.ResultsPatients of the SGLT-2i group experienced similar symptomatic hypoglycemic episodes (15.9%) as the sitagliptin group. There was an improvement in blood sugar levels after the use of SGLT-2i (RBS 181 ± 64 before Ramadan vs 162 ± 53 after Ramadan). HbA1c also improved after the use of SGLT-2i before and after Ramadan (7.2 ± 0.8 vs 6.9 ± 0.9 for Metformin + Empagliflozin and 7.8 ± 1.5 vs 7.6 ± 1.6 for Metformin and sitagliptin). Weight and BMI improved after the use of SGLT-2i (BMI 36.5 ± 4.8 before Ramadan and 33.7 ± 2.4 after Ramadan). There were no reported cases of urinary tract infection in the empagliflozin group.ConclusionSGLT-2 inhibitors combined with metformin for patients with diabetes during Ramadan fasting is as effective, safe and well tolerated as DPP4 combined with metformin.

Insulinoma-related Endogenous Hypoglycaemia with a Negative Fasting Test: A Case Report and Literature Review.

We present the case of a patient with a history of symptomatic hypoglycaemic episodes and a negative 72-hour fasting test with histological confirmation of insulinoma. A literature review of hyperinsulinaemic hypoglycaemia with a negative fasting test was performed.LEARNING POINTSThe 72-hour fasting test is the gold standard for insulinoma diagnosis.Few cases of insulinoma with a negative fasting test have been reported.New strategies for insulinoma diagnosis are being investigated.

Comparison of the safety and clinical efficacy of glucagon-like peptide-1 receptor agonist and α-glucosidase inhibitor among Chinese people with type 2 diabetes

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To compare the safety and efficacy of once-weekly prescription of GLP-1 receptor agonists (adlyxin) with those of α-glucosidase inhibitor (voglibose) and other reference drugs (RD).&#x0D; Methods: A total of 1250 stable diabetes-mellitus patients from the Department of Endocrinology, Ningbo No. 6 Hospital, Ningbo, Zhejiang 315040, China were enrolled in this study between Feb 2018 and Jan 2020. They were treated using physical exercise and diet chart therapy. The patients were assigned to three different groups and administered GLP-1 receptor agonist (GLP-1RA) or glucosidase inhibitor (voglibose) and other reference drugs (RDs). The safety and efficacy of these drugs were compared. The primary endpoint was the number of treatment-emergent adverse events (TEAEs), while the secondary endpoints were based on symptomatic hypoglycaemic episodes and other biochemical parameters.&#x0D; Results: Patients who used α-glucosidase inhibitors had the highest percentage of TEAEs, when compared to those on GLP-1RAs and RDs (p &lt; 0.05). No specific cases of severe hypoglycaemia were observed among all the groups. Users of adlyxin also achieved significant glycaemic control at the end of the study period, when compared to voglibose users, with a mean HbA1c baseline of 8.2 % (p &lt; 0.05).&#x0D; Conclusion: These results indicate that the GLP-1 receptor agonist adlyxin achieved good glycaemic control. Thus, it has beneficial potential for use among type 2 diabetes in the Chinese population.&#x0D; &#x0D; &#x0D; &#x0D;

Comparison of treatment with insulin degludec and glargine U100 in patients with type 1 diabetes prone to nocturnal severe hypoglycaemia: The HypoDeg randomized, controlled, open-label, crossover trial.

AimTo investigate whether the long‐acting insulin analogue insulin degludec compared with insulin glargine U100 reduces the risk of nocturnal symptomatic hypoglycaemia in patients with type 1 diabetes (T1D).MethodsAdults with T1D and at least one episode of nocturnal severe hypoglycaemia during the last 2 years were included in a 2‐year prospective, randomized, open, multicentre, crossover trial. A total of 149 patients were randomized 1:1 to basal‐bolus therapy with insulin degludec and insulin aspart or insulin glargine U100 and insulin aspart. Each treatment period lasted 1 year and consisted of 3 months of run‐in or crossover followed by 9 months of maintenance. The primary endpoint was the number of blindly adjudicated nocturnal symptomatic hypoglycaemic episodes. Secondary endpoints included the occurrence of severe hypoglycaemia. We analysed all endpoints by intention‐to‐treat.ResultsTreatment with insulin degludec resulted in a 28% (95% CI: 9%‐43%; P = .02) relative rate reduction (RRR) of nocturnal symptomatic hypoglycaemia at level 1 (≤3.9 mmol/L), a 37% (95% CI: 16%‐53%; P = .002) RRR at level 2 (≤3.0 mmol/L), and a 35% (95% CI: 1%‐58%; P = .04) RRR in all‐day severe hypoglycaemia compared with insulin glargine U100.ConclusionsPatients with T1D prone to nocturnal severe hypoglycaemia have lower rates of nocturnal symptomatic hypoglycaemia and all‐day severe hypoglycaemia with insulin degludec compared with insulin glargine U100.

Type 2 diabetes mellitus and risk of Alzheimer's disease

The evidences like biological and epidemiological support a link between type 2 diabetes mellitus (DM2) and Alzheimer's disease (AD). Persons with diabetes have a higher rate of cognitive decline and an increased risk of developing dementia of all types. Cognitive deficits in diabetic people get mainly affect the psychomotor efficiency areas like attention, learning and memory, mental ability, flexibility and speed, and executive function. The concrete epidemiological association has suggested the existence of a pathophysiological link. The factors of increased cognitive decline in DM2, however, are less clear. Increased atrophy of cortical and subcortical areas had clearly shows after controlling for diabetic vascular disease and inadequate circulation in cerebral areas.Most recent studies have focused on the role of insulin and insulin resistance as possible links between diabetes and AD. Disturbances in brain insulin signaling mechanisms may contribute to the molecular, biochemical, and histopathological lesions in AD. Hyperglycemia itself is a risk factor for cognitive dysfunction and dementia. Hypoglycemia may also have deleterious effects on cognitive function. Recurrent symptomatic and asymptomatic hypoglycemic episodes have been suggested to cause sub-clinical brain damage, and permanent cognitive impairment. Future trials are required to clarify the mechanistic link, to address the question whether cognitive decline may be prevented by an adequate metabolic control, and to elucidate the role of drugs that may cause hypoglycemic episodes.

A novel mutation in ACADVL causing very long-chain acyl-coenzyme-A dehydrogenase deficiency in a South Asian pediatric patient: a case report and review of the literature

BackgroundVery long-chain acyl-coenzyme-A dehydrogenase deficiency is a rare, severe life-threatening metabolic disorder of mitochondrial fatty acid oxidation, caused by mutations in ACADVL gene. Here we present a genetically confirmed case of a South Asian baby girl with severe, early-onset form of very long-chain acyl-coenzyme-A dehydrogenase deficiency due to a novel mutation in ACADVL gene.Case presentationIndex case was the second baby girl of second-degree consanguineous South Asian parents. She had an uncomplicated antenatal period and was born by spontaneous vaginal delivery at term with a birth weight of 2910 g. She had been noted to have fair skin complexion, hypotonia, and 3 cm firm hepatomegaly. Since birth, the baby developed grunting, poor feeding, and recurrent episodes of symptomatic hypoglycemia and convulsions with multiple semiology. Her septic screening and urine ketone bodies were negative. The baby had high anion gap metabolic acidosis and elevated transaminases and serum creatine phosphokinase levels. Echocardiogram at 4 months revealed bilateral ventricular hypertrophy. Acylcarnitine profile revealed elevated concentrations of tetradecanoylcarnitine (C14), tetradecanoylcarnitine C14:1, and C14:1/C16. Unfortunately, the baby died due to intercurrent respiratory illness at 4 months of age. Sequence analysis of ACADVL gene in perimortem blood sample revealed homozygous frame shift novel variant NM_001270447.1, c.711_712del p.(Phe237Leufs*38), which confirmed the diagnosis of very long-chain acyl-coenzyme-A dehydrogenase deficiency.ConclusionsThis case demonstrates the importance of early diagnosis and management of very long-chain acyl-coenzyme-A dehydrogenase deficiency in improving the outcome of the patients. Implementation of newborn screening using tandem mass spectrometry in Sri Lanka will be beneficial to reduce the morbidity and mortality of treatable disorders of inborn errors.

Glycemic control status, diabetes management patterns, and clinical characteristics of adults with type 1 diabetes in Japan: Study of Adults' Glycemia in T1DM subanalysis.

Type 1 diabetes is rare in the general Japanese population, but becoming more common in adults with increased longevity owing to advancements in treatment. We aimed to examine the current state of glycemic control and diabetes management using real-world data on Japanese adults with type 1 diabetes in different age groups. This was a subanalysis of Japanese participants from a multinational, cross-sectional, observational study of adults with type 1 diabetes aged ≥ 26years conducted in 2018 (Study of Adults' Glycemia in T1DM). Glycemic control achievement rate and goal setting, incidence of hypoglycemia, and diabetes management of individuals aged 26‒44years, 45‒64years, and ≥ 65years were summarized. The data on 528 participants were analyzed. The mean glycated hemoglobin (HbA1c) value was 7.8% (61.3mmol/mol). Of the participants, 25.8% achieved an HbA1c level of < 7.0% (26-44years, 33.7%; 45‒64years, 18.9%; and ≥ 65years, 24.3%). In total, 71.4% participants reported ≥ 1 symptomatic hypoglycemic episode within the last 3months, and 5.5% participants reported ≥ 1 severe hypoglycemic episode within the last 6months. A less stringent individualized goal was set for participants aged ≥ 65years; they had the lowest incidence of ≥ 1 symptomatic hypoglycemic episode. Insulin pumps and continuous glucose monitoring were used in 23.5% and 33.9% participants, respectively. Glycemic control was suboptimal; the low incidence of severe hypoglycemia suggests careful glycemic control, balancing benefits and risks, particularly in Japanese adults aged ≥ 65years with type 1 diabetes. The online version contains supplementary material available at 10.1007/s13340-021-00504-7.

Effectiveness of Liver-Directed Therapy for the Management of Intractable Hypoglycemia in Metastatic Insulinoma.

The aim of the study was to evaluate efficacy of chemoembolization and radioembolization in treating patients with recurrent hypoglycemia secondary to metastatic insulinoma. A retrospective review was performed of all patients with metastatic insulinoma treated with liver-directed therapy (LDT) at a large academic medical center from January 1998 to August 2017. Primary outcomes included blood glucose levels, occurrence of symptomatic hypoglycemic episodes, and tumor imaging response rates. Seven patients were identified (4 male patients). The mean age at the first LDT was 60.9 (standard deviation [SD], 9.2) years. The median follow-up was 1.8 years. Thirty-three sessions of LDT were performed including 30 sessions of chemoembolization and 3 sessions of radioembolization. Technical success rate was 97% (32/33 procedures) with an initial clinical success rate of 100%, defined as absence of recurrent symptomatic hypoglycemia within 1 month after first cycle of LDT and overall clinical success rate of 85%. Random daytime glucose levels increased from 75.0 (SD, 26) mg/dL to 152.8 (SD, 52.4) mg/dL after LDT. The mean time to recurrence of intractable hypoglycemia was 21 (SD, 9) months. No severe complications were reported. Liver-directed therapy with chemoembolization or radioembolization is effective for treatment of symptomatic hypoglycemia secondary to malignant insulinoma metastatic to liver.

Efficacy of Combination of Insulin Glargine with either Metformin or Sulfonylurea in Patients with Poorly Controlled Type 2 Diabetes

Background: Although adding insulin glargine to oral antidiabetic drugs (OADs) has demonstrated efficacy in patients with type 2 diabetes, evidence supporting specific regimens is lacking. The aim of this study was to compare the efficacy of combination therapy of insulin glargine with either sulfonylurea (SU) or metformin (Met) in patients with poorly controlled type 2 diabetes receiving ≥ 2 OADs. Methods: This was a 48-week prospective, open-label, randomized, parallel trial. Patients with type 2 diabetes poorly controlled with ≥ 2 OADs were randomized to the insulin glargine with Met (Met-group) or insulin glargine with SU (SU-group). Results: Mean glycosylated hemoglobin (A1C) reduction were significant in the Met-group and SU-group (-1.42 ± 0.28% and -1.00 ± 0.28%, respectively), but no statistically significant difference between groups (-0.40 ± 0.3%, p = 0.234). There was no difference in the proportion of patients achieving A1C of ＜ 7% (12.8% and 6.8%, respectively).Mean FPG reduced significantly in both groups (-120.3 ± 8.8 mg/dL and -90.2 ± 11.1mg/dL, respectively), with greater reductions in the Met-group (-34.8 ± 10.0mg/dL, p ＜ 0.001). More proportions of patients in the Met-group achieved the FPG target of ＜ 130 mg/dL (80.9% and 40.9%, respectively, p ＜ 0.001). The percentages of patients experiencing episodes of symptomatic hypoglycemia (Met-group: 23.4%, SU-group: 19.6%) and the percentages of nocturnal hypoglycemia (Met-group: 8.5%, SU-group: 6.5%) were similar among the two groups. Conclusion: In patients with type 2 diabetes poorly controlled on ≥ 2 OADs, glycemic control was comparable among the two regimens.

Improving interpretability of individual Diabetes Symptom Checklist-Revised (DSC-R) scores: the role of patient characteristics

IntroductionThe Diabetes Symptom Checklist-Revised (DSC-R) is a well-validated patient-reported outcome designed to assess symptom burden in persons with type 2 diabetes mellitus (T2DM) across eight domains. The DSC-R has so...