Despite the increasing number of patients diagnosed with postprandial reactive hypoglycemia (PRH), standardized diagnostic criteria and evaluation methods have not been established. Since PRH is generally defined as “hypoglycemia occurring due to elevated endogenous insulin levels following a high-carbohydrate meal in people without diabetes mellitus”, prediabetes is considered one of the obvious pathologies of PRH. However, it has recently been reported that early diabetes can enter a state of “remission”; therefore, it is difficult to distinguish between prediabetes and early diabetes. We present a case of PRH in an obese woman with prediabetes, identified through oral glucose tolerance testing and continuous glucose monitoring. She experienced severe hypoglycemia, which sometimes resulted in loss of consciousness. However, her PRH symptoms were effectively treated with an α-glucosidase inhibitor. We believe it would be beneficial for clinicians to study this case, as it clearly demonstrates a pathology of PRH in a patient with prediabetes and/or early diabetes.
Lipohypertrophy (LH) is a common complication of insulin-treated diabetes; however, its prevalence and risk factors in people using continuous subcutaneous insulin infusion (CSII) remain insufficiently characterized. This study aimed to determine the prevalence and severity of LH and to identify the associated risk factors in individuals with type 1 diabetes mellitus (T1DM) treated with CSII or multiple daily injections (MDI). A total of 121 individuals with T1DM who received insulin therapy for at least one year were included (CSII, n = 43; MDI, n = 78). The presence and severity of LH (non-LH, mild, moderate, or severe) were assessed using the methods described by Ucieklak et al. Clinical characteristics were extracted from medical records, and diabetes self-management variables were collected using self-reported questionnaires. The distribution of LH severity did not differ significantly between the CSII and MDI groups (CSII: 41.9
Continuous glucose monitoring (CGM) has enabled increasingly stringent assessment of glycemic control beyond conventional time in range (TIR; 70–180 mg/dL). Time in tight range (TITR), defined as the percentage of time with glucose levels between 70 and 140 mg/dL, was proposed in 2023 as a more stringent CGM-derived metric. This review summarizes current evidence regarding the clinical significance and limitations of TITR. TITR correlates strongly with HbA1c and TIR, and may be more sensitive than TIR to changes in mean glucose when glycemia approaches the normal range. Recent cohort studies suggest that lower TITR is linearly associated with higher risks of all-cause and cardiovascular mortality, while higher TITR is associated with lower incidence of diabetic retinopathy. TITR has also shown associations with favorable outcomes in COVID-19 pneumonia. However, its interpretation requires caution because glycemic variability can influence TITR differently according to mean glucose levels. In individuals with type 1 diabetes treated with multiple daily injections, higher TITR may be accompanied by increased time below range, suggesting that indiscriminate pursuit of higher TITR could increase hypoglycemia risk. Further prospective studies are needed to establish optimal TITR targets and determine whether TITR provides prognostic value beyond established CGM metrics across diverse populations.
In older adults with diabetes, HbA1c below the lower limit of individualized targets may reflect intensive or potentially excessive treatment rather than favorable glycemic control. The association between this status and diabetes-related cost remains unclear. We examined the association between HbA1c status relative to individualized targets and estimated 28-day diabetes-related cost. This single-center cross-sectional study included 117 outpatients aged ≥ 65 years. Patients were classified as below the lower limit, within/meeting the individualized target, or above the target. Diabetes-related cost, defined as net drug cost plus diabetes-related care management fees, was the primary outcome; net drug cost was analyzed as a component of this outcome. Medication costs were standardized to 28 days. We performed group comparisons and exploratory multivariable regression using ln-transformed diabetes-related cost. Sensitivity analysis using ln(cost + 1) included zero-cost patients. Nine patients were below the lower limit, 60 were within/meeting the target, and 48 were above the target. Median diabetes-related cost was highest in the below-lower-limit group, followed by the above-target and within/meeting-target groups (27,075, 10,732, and 3,663 JPY/28 days, respectively; p < 0.001). In exploratory regression excluding zero-cost patients, the adjusted cost ratio for below-lower-limit versus within/meeting-target status was 2.03 (95
Anti-glutamic acid decarboxylase antibody-associated cerebellar ataxia (anti-GAD-CA) is a rare autoimmune neurological disorder. Although frequently associated with latent autoimmune diabetes in adults (LADA), it can occasionally coexist with type 1 diabetes mellitus (T1DM). We report a 27-year-old woman with a 14-year history of T1DM who presented with subacute onset of balance impairment, vertigo, and hypophonic speech. Neurological examination and laboratory investigations were consistent with cerebellar ataxia. The patient exhibited high titers of anti–glutamic acid decarboxylase (anti-GAD) in both serum (619 IU/mL) and cerebrospinal fluid. Brain MRI was unremarkable. After a 5-day intravenous immunoglobulin (IVIG) therapy, the patient showed notable improvement in tandem gait and speech fluency. Her glycemic control also improved significantly, with the glycated hemoglobin (HbA1c) dropping from 9.7 to 6.8
Cases involving both diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) may present with a more severe condition at the start of treatment compared to cases involving either condition alone. However, gastrointestinal infections are a relatively rare cause of mixed DKA/HHS in adults. A 66-year-old man with untreated diabetes was admitted with impaired consciousness after several days of diarrhea and poor oral intake. Laboratory findings confirmed mixed DKA/HHS; blood cultures identified Aeromonas caviae (A. caviae), and stool cultures identified Escherichia coli (E. coli) O125. Mixed DKA/HHS and infection resolved following continuous intravenous insulin, fluid resuscitation, and appropriate antimicrobial therapy, but refeeding syndrome developed. In cases of malnutrition or hyperglycemia, an immunocompromised state serves as a risk factor for multiple infections. If concomitant infections or microbiological findings are present, they may exacerbate metabolic decompensation in mixed DKA/HHS. To our knowledge, this is the first reported case of adult mixed DKA/HHS associated with A. caviae bacteremia and pathogenic E. coli O125 detected in stool. Clinicians should be aware that gastrointestinal infections can trigger DKA and consider the possibility of concomitant infections and bacteremia.
Diabetic ketoacidosis remains a significant concern among pediatric patients with diabetes. Ramadan and associated lifestyle changes in pediatric patients (sleeplessness and metabolic stress-intermittent dehydration) should increase the risk of diabetes emergencies. This study aimed to investigate the specific characteristics of diabetic ketoacidosis (DKA) episodes among pediatric patients with diabetes during the fasting month of Ramadan. Research Design and Methods: A bicentric retrospective analysis was conducted on pediatric patients with DKA admitted to the hospitals (Mouwasat hospital Dammam and khobar,ksa) during a four-year period relative to Ramadan. DKA episodes were categorized as mild, moderate, or severe DKA,and according to corrected electrolyte disturbance in many subcategories (hypernatremic, hyponatremic, or isonatremic DKA and as hypokalemic, normokalemic, or hyperkalemic DKA). A comparative analysis was then performed between two groups defined according to the time of occurrence of DKA during the lunar years: the Ramadan group and the non-Ramadan group. The median age of patients who presented with DKA during Ramadan was [8 (6–11)], with [55
Women diagnosed with gestational diabetes mellitus (GDM) before 24 weeks of gestation may have an increased postpartum risk of abnormal glucose tolerance (AGT); however, factors associated with this outcome are unclear. This study aimed to identify factors associated with AGT at 6–12 weeks postpartum in women diagnosed with GDM before 24 weeks of gestation. This single-center retrospective study analyzed patients diagnosed with GDM before 24 weeks of gestation. Postpartum 75-g oral glucose tolerance test (OGTT) results classified participants as AGT (borderline or diabetic) or normal glucose tolerance (NGT). Factors associated with postpartum AGT were examined using multivariate logistic regression analysis. A total of 164 women with GDM were included in this analysis. Postpartum AGT developed in 68 (41.5
We describe a case of severe hypoglycemia induced by postoperative renal dysfunction associated with prolonged unrecognized cibenzoline intoxication. An 83-year-old woman with type 2 diabetes mellitus (T2DM) developed severe hypoglycemia after orthopedic surgery and was diagnosed with cibenzoline intoxication on the basis of a markedly elevated serum cibenzoline concentration. Cibenzoline discontinuation resolved hypoglycemia and improved bradycardia. Pre-existing bradycardia during cibenzoline therapy and preoperative elevated levels of serum C-peptide were suggestive of unrecognized intoxication. This case provides significant clinical insight by documenting the longitudinal evidence of unrecognized cibenzoline intoxication in a patient with T2DM, which remained latent until the acute manifestation of hypoglycemia. Insulin resistance in diabetes may delay the manifestation of hypoglycemia. While the measurement of cibenzoline concentration is the primary method for monitoring toxicity, the electrocardiogram and C-peptide assessments offer significant supplementary data for diabetic patients. C-peptide measurement is not performed routinely but should be assessed by blood testing when cibenzoline intoxication is suspected from electrocardiographic findings.
The management of type 2 diabetes (T2D) has entered a new era with the advent of advanced incretin-based therapies. Therapeutic agents such as semaglutide and tirzepatide have demonstrated exceptional efficacy in improving glycemic control, inducing substantial weight loss, and reducing cardiometabolic risk, thereby redefining therapeutic expectations. Yet, dulaglutide retains a distinct role supported by its strong cardiovascular evidence base. The REWIND trial remains the only GLP-1 receptor agonist study to show a statistically significant reduction in major adverse cardiovascular events (MACE) in a predominantly primary prevention population, with durable benefit sustained over more than five years of follow-up. Comparative trials highlight that while tirzepatide and semaglutide deliver superior reductions in HbA1c and body weight, dulaglutide offers proven cardiovascular safety, favourable tolerability, and high persistence in real-world analyses. Its once-weekly, fixed-dose regimen requires no titration and is accessible across diverse healthcare systems in low- and middle-income countries, including those constrained by cost or resources. The SURPASS-CVOT established tirzepatide’s non-inferiority to dulaglutide for cardiovascular outcomes, reaffirming dulaglutide as an established comparator with robust outcome data. This narrative review collates evidence in this regard and argues that dulaglutide should be viewed not as superseded but as complementary offering a pragmatic balance of efficacy, safety, and accessibility that supports equitable cardiometabolic care worldwide.
Sarcopenia is classified into normal, presarcopenia, dynapenia, and sarcopenia according to muscle strength/mass. As assessment methods for muscle strength and mass, phase angle (PhA), extracellular water/intracellular water ratio (ECW/ICW), and advanced glycation end products (AGEs) have been developed. We investigated the proportions in elderly outpatients with diabetes and elucidate clinical characteristics, including PhA, ECW/ICW, and AGEs among the four groups. A cross-sectional study was performed in 695 patients with diabetes aged 65 years or older, who were classified according to the classification proposed by the Asian Working Group for Sarcopenia. Clinical characteristics of the four groups were compared by ANOVA. Associations of grip strength and skeletal muscle index (SMI) with PhA, ECW/ICW, and AGEs and interrelations among grip strength, SMI, PhA, ECW/ICW, and AGEs were analyzed by multiple linear regression analyses. Proportions of those (male/female,
This study aimed to develop and validate a brief 5-item version of the Hypoglycemia Problem-Solving Scale (HPSS-5) and a single-item screening tool (HPSS-1) for the rapid assessment of hypoglycemia problem-solving ability in adults with type 1 diabetes. In this post-hoc analysis of the PR-IAH study, data from 233 adults with type 1 diabetes were analyzed to examine reliability and validity. Internal consistency, construct validity, and discriminative performance were evaluated using confirmatory factor analysis (CFA) with a robust estimator and receiver operating characteristic (ROC) analysis. Participants with high and low hypoglycemia problem-solving ability accounted for 17.2
The aim of this study was to examine sex differences in insulin resistance and basal insulin secretion among elderly individuals without a history of diabetes, comparing obese and non-obese groups in early elderly (aged 65–74 years) and late elderly (aged 75–89 years). A total of 478 individuals (258 men and 220 women) who underwent comprehensive medical checkups at Tsunan Municipal Hospital between 2008 and 2014 were included. We investigated whether there were interactive effects between age and Body Mass Index (BMI) on homeostasis model assessment of insulin resistance (HOMA-IR) values and homeostasis model assessment of beta cell function (HOMA-β) values, and examined their associations with each factor using analysis of variance (ANOVA) and multivariate analysis. In elderly men, elevated BMI was significantly associated with higher HOMA-IR values, and HOMA-β values were also significantly higher in the obese group than in the non-obese group. In contrast, among elderly women, HOMA-β values in the obese group were comparable to those in the non-obese group regardless of early and late elderly. In elderly men, insulin resistance associated with obesity was firmly present regardless of age, whereas, in elderly women, there is no difference in basal insulin secretion between the obese and non-obese groups irrespective of age.
To evaluate the real-world efficacy of sensor-augmented pump (SAP) for long-term glycemic control and glycemic variability indices. This was a single-center, retrospective, observational study that included individuals with type 1 diabetes who switched from multiple daily injections to SAP or continuous subcutaneous insulin infusion (CSII). Changes in HbA1c and body weight up to 3 years were compared between the two groups. Changes in the proportion of participants in each group were also analyzed. In the SAP group, changes in continuous glucose monitoring (CGM) metrics were also examined. There were 32 individuals in the SAP group and 39 in the CSII group. HbA1c decreased significantly in both groups at 1 year compared with the pre-introduction levels and was maintained for 3 years (− 0.83 ± 0.26
A 67-year-old woman with a 25-year history of type 1 diabetes mellitus and comorbid Crohn’s disease developed rapidly progressive proteinuria, hypoalbuminemia, edema, and kidney dysfunction. Minimal change disease (MCD) was diagnosed on kidney biopsy. Mesalazine was discontinued, and prednisolone (PSL) at 50 mg/day (0.9 mg/kg) induced remission of MCD. During treatment, glycemic management markedly worsened, and multiple daily insulin injections failed to achieve adequate control. After edema improved and PSL was tapered to 35 mg/day, continuous subcutaneous insulin infusion was resumed, and advanced hybrid closed-loop (AHCL) therapy was initiated using the MiniMed™ 780G system. Consequently, time in range markedly increased, accompanied by a significant decrease in time above range without a clinically significant increase in time below range. During PSL tapering, hypoglycemia was successfully prevented through automated basal rate adjustment by the AHCL system, optimization of the carbohydrate-to-insulin ratio, extension of active insulin time, setting of temporary glucose targets, and supplemental carbohydrate intake. This case suggests that MCD should be considered in the differential diagnosis of patients with Crohn’s disease or diabetes presenting with rapidly progressive proteinuria and kidney impairment. To prevent hypoglycemia and mitigate the limitations of automated delivery, device settings should be dynamically adjusted during steroid tapering to account for changes in insulin sensitivity. With this clinical management strategy, AHCL therapy may be an effective treatment option for steroid-induced hyperglycemia.
Ketogenic diet (KD) therapy is effective for refractory epilepsy but significantly impacts carbohydrate and lipid metabolism. We previously encountered a patient who developed diabetes during KD; metabolic abnormalities were undetected by conventional criteria for diabetes, suggesting standard criteria are inapplicable. This study aimed to establish specialized metabolic reference ranges for patients on KD. We retrospectively analyzed laboratory data from 18 pediatric patients with refractory epilepsy treated with KD. Geometric means and reference ranges (mean ± 2SD) were calculated using mixed-effects models to account for repeated measures. Before KD, geometric means (reference ranges) were: random plasma glucose (RPG), 96.7 (79.1–118.3) mg/dL; HbA1c (NGSP), 4.76
Diabetic retinopathy (DR), a complication of type 2 diabetes (T2DM), can lead to vision loss if undetected. This review examines how social determinants of health (SDOH) influence DR prevalence and screening. Following PRISMA guidelines and PROSPERO registration (CRD42024603749), this review searched four databases through October 26, 2024, for studies on SDOH and DR. Titles, abstracts, and full texts were screened, risk of bias was assessed with the EPHPP tool, and pooled effect sizes were calculated using a random-effects model with 95
The association between decreased zinc and poor glycemic control has been revealed in diabetic patients. However, the involvement of zinc in glucose metabolism in healthy, non-diabetic individuals remains unclear. Company T employees and their spouses who underwent the milestone-age health checkups at the Tokyo Health Service Association were recruited in the study (n = 533). The following variables were obtained from blood and urine samples and questionnaires: three zinc measures (serum zinc, urinary zinc, and zinc intake); two obesity-related measures (visceral fat and adiponectin); three insulin-related measures (insulin, HOMA-β, and HOMA-IR); and two glucose-related measures (fasting plasma glucose and HbA1c). Correlation analysis between zinc measures revealed a significant correlation between serum zinc and urinary zinc, but not between the other pairs. Correlation analysis between zinc measures and obesity-, insulin-, and glucose-related measures revealed weak but significant correlations between serum zinc and adiponectin and HbA1c, as well as between urinary zinc and fasting plasma glucose and HbA1c. A path analysis using structural equation modeling confirmed that serum zinc was directly linked to urinary zinc and adiponectin, which affected blood glucose levels (HbA1c) directly and indirectly by influencing insulin secretion function (HOMA-β). This is the first study to statistically demonstrate the pathway linking zinc to blood glucose levels in healthy, non-diabetic adults using objective measurement data. Decreased serum zinc levels were associated with reduced adiponectin concentrations and impaired insulin secretion function, which may have contributed to elevated blood glucose levels.
The purpose of this study is to investigate the impact of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on lower urinary tract symptoms (LUTS) in individuals with type 2 diabetes mellitus (T2DM). While SGLT2i are effective antidiabetic agents with cardiovascular and renal benefits, concerns remain about their impact on LUTS. This prospective observational study included 47 patients with T2DM without organic urinary tract disease or autonomic neuropathy. The Overactive Bladder (OAB)-Validated 8-question (OAB-V8) questionnaire was administered at baseline and reassessed at months 1 and 3 of SGLT2i treatment. The associations of alterations in symptom scores with metabolic parameters were assessed using Spearman’s rank correlation. The mean overall OAB-V8 score decreased from 10.1 ± 5.0 to 8.8 ± 6.5 at month 1 (p = 0.01), with no significant difference at month 3 (p = 1.00). Subgroup analyses suggested transient improvement in patients with OAB (n = 17), with scores decreasing from 15.4 ± 4.0 to 12.4 ± 5.7 at month 1 (p = 0.04), followed by a return to baseline at month 3 (16.0 ± 9.0; p = 0.69). Patients without OAB (n = 30) showed stable scores at month 1 (7.1 ± 2.3 to 6.9 ± 6.1; p = 0.24) and dropped significantly by month 3 (6.6 ± 5.4; p = 0.03). Changes in overall scores were independent of body mass index or glycated hemoglobin levels, both in patients with and without OAB. Short-term SGLT2i therapy did not appear to worsen OAB symptoms in patients with T2DM. The results of the subgroup analyses should be viewed cautiously and validated in studies with larger populations. These results provide preliminary reassurance but highlight the need for larger, controlled studies with longer follow-up.
