Neutrophil-to-Lymphocyte Ratio as a Potential Biomarker to Managing Type 2 Diabetes Mellitus and Predicting Disease Progression.

Introduction Diabetes is a chronic disease that causes dysregulation of blood glucose. Type 2 diabetes mellitus (T2DM) could result in long-term inflammatory conditions that affect different organs of the body. Despite the availability of diagnostic markers like glycated hemoglobin (HbA1c) for T2DM, it is essential to find an appropriate marker that could predict long-term complications. This study evaluates the potential role of neutrophil-to-lymphocyte ratio (NLR) in predicting disease progression and treatment responses.  Methods This case-control study was carried out among 160 T2DM patients and 132 non-diabetic persons. Blood samples were collected from each participant and were processed for hemoglobin, HbA1c, iron, ferritin, and complete blood picture (NLR).  Results The study showed that there was a significant variation in the serum levels of ferritin (264.8±611.6 ng/ml versus 168.3±364.7 ng/ml, p=0.392), iron (4.095±8.851 mcg/dl versus 55.20±37.62 mcg/dl, p=0.0111), and HbA1c (8.169±1.635% versus 5.668±0.5260% p<0.0001) among T2DM patients compared to non-diabetic persons. The NLR values (4.189±4.154 versus 4.095±8.851, p=0.009) among patients with T2DM significantly varied with that of non-diabetic persons. A significant negative correlation was noticed between the serum levels of iron and NLR (r=-0.17, p=0.014) and a positive correlation was noticed between HbA1c and NLR (r=0.19, p=0.014). The serum levels of iron revealed a significant positive correlation with the serum levels of ferritin (r=0.24, p=0.002) and hemoglobin percentage (r=0.41, p=0.008). HbA1c revealed a significant positive correlation with NLR (r=0.19, p=0.014). Additionally, a significant negative correlation was observed between iron with NLR (r=-0.17, p=0.029) and hemoglobin percentage with NLR (r=-0.30, p=0.005). However, no such correlation was demonstrated among non-diabetic persons. With an accuracy of 89.85% and high sensitivity and specificity, NLR showed diagnostic accuracy like HbA1c.  Conclusions NLR demonstrated equivalent efficacy to HbA1c in predicting glycemic control. Since diabetes affects different organs of the body, evaluating NLR probably predicts inflammation. Therefore, NLR could be useful in the management of T2DM and in predicting long-term complications.

Association of HbA1c and utilization of internal mammary arteries with wound infections in CABG.

Background: Deep sternal wound infection (DSWI) remains a serious complication after coronary artery bypass grafting (CABG). We herein aimed to stratify diabetic patients who underwent CABG using bilateral internal mammary artery (BIMA) for levels of glycated hemoglobin A1C (HbA1c) and compare postoperative outcomes. Methods: Between January 2010 and August 2020, 4,186 consecutive patients underwent isolated CABG at our center. In 3,229 patients, preoperative HbA1c levels were available. Primary endpoints were wound healing disorder (WHD), DSWI, and 30-day mortality. Patients were stratified according to preoperative HbA1c levels. Patients were further divided into subgroups according to utilization of BIMA. Results: After adjustment, no differences in mortality and stroke rates were seen between group 1 (HbA1c < 6.5%) vs. group 2 (HbA1c ≥ 6.5%). WHD was more frequent in group 2 [2.8 vs. 5.6%; adjusted p = 0.002; adjusted odds ratio (OR), 1.853 (1.243-2.711)] but not DSWI [1.0 vs. 1.5%; adjusted p = 0.543; adjusted OR, 1.247 (0.612-2.5409)]. BIMA use showed a higher rate of WHD [no BIMA: 3.0%; BIMA: 7.7%; adjusted p = 0.002; adjusted OR, 4.766 (1.747-13.002)] but not DSWI [no BIMA: 1.1%; BIMA: 1.8%; adjusted p = 0.615; adjusted OR, 1.591 (0.260-9.749)] in patients with HbA1c ≥ 6.5%. Conclusions: Intraoperative utilization of BIMA is not connected with an increase of DSWI but higher rates of WHD in patients with poor diabetic status and HbA1c ≥ 6.5%. Therefore, application of BIMA should be taken into consideration even in patients with poor diabetic status, while identification of special subsets of patients who are at particular high risk for DSWI is of paramount importance to prevent this serious complication.

Evaluation of effects from hemoglobin variants on HbA1c measurements by different methods.

OBJECTIVES: The impact of seven hemoglobin variants (Hb Q-Thailand, Hb G-Honolulu, Hb Ube-2, Hb New York, Hb J-Bangkok, Hb G-Coushatta, and Hb E) on the outcome of HbA1c was investigated for six methods by comparing with liquid chromatography-tandem mass spectrometry (LC/MS/MS) reference method. METHODS: Twenty-nine normal and 112 variant samples were measured by LC/MS/MS, Sebia Capillarys 3 TERA, Intelligene Biosystems QuanTOF, Premier Hb9210, Arkray HA-8190V, Bio-Rad D-100, and Tosoh G11, then evaluated for correlation, consistency, and mean relative bias among six methods. The lowest biological variation bias of ±2.8 % was an acceptable standard. RESULTS: All methods showed poor correlation and consistency with LC/MS/MS for Hb E. The unacceptable biases were observed for Capillarys 3 TERA (-14.4 to -3.7 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), QuanTOF (-8.3 to -2.9 % for Hb Ube-2, Hb New York and Hb G-Coushatta), Premier Hb9210 (-18.3 to -3.6 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), HA-8190V variant mode (-17.3 to 6.6 % for Hb G-Honolulu, Hb Ube-2, Hb New York, Hb G-Coushatta and Hb E). All variant samples showed larger biases than ±2.8 % comparing HA-8190V fast mode, D-100, and G11 with LC/MS/MS. CONCLUSIONS: The accuracy of different HbA1c methods was influenced by some Hb variants, especially Hb Ube-2 and Hb New York. Thus, laboratories need to choose appropriate methods to measure HbA1c with different Hb variants.

Quality assessment of glucose measurement with regard to epidemiology and clinical management of diabetes mellitus in Germany.

Background: During the last decade, Germany has seen an increased prevalence and a redistribution from undetected to diagnosed diabetes mellitus. Due to this substantial epidemiological development, the number of people with documented type 2 diabetes was 8.7 million in 2022. An estimated two million undiagnosed subjects are to be added. Beyond that, the life expectancy of diabetic subjects is increasing due to more responsive health systems in terms of care. Possible reasons include improved screening of at-risk individuals, the introduction of HbA1c for diagnosis in 2010, and the higher use of risk scores. Additionally, quality aspects of the laboratory methodology should be taken into consideration. Methods: Epidemiology and clinical management of diabetes in Germany are presented in the light of publications retrieved by a selective search of the PubMed database. Additionally, the data from German external quality assessment (EQA) surveys for the measurands glucose in plasma and HbA1c in whole blood, reviewed from 2010 until 2022, were evaluated. Above this, data concerning the analytical performance of near-patient glucometer devices, according to the ISO norm 15197:2013, were analyzed. Results: Two laboratory aspects are in good accordance with the observation of an increase in the diabetes mellitus prevalence when retrospectively reviewing the period 2010 to 2022: First, the analytical performance according to the ISO norm 15197:2013 of the glucometer devices widely used by patients with diabetes for the glucose self-testing, has improved during this period. Secondly, concerning the EQA program of INSTAND, the number of participating laboratories raised significantly in Germany. The spreads of variations of the specified results for plasma glucose remained unchanged between 2010 and 2022, whereas for HbA1c a significant decrease of the result scattering could be observed. Conclusion: These retrospectively established findings testify to an excellent analytical quality of laboratory diagnostics for glucose and HbA1c throughout Germany which may be involved in a better diagnosis and therapy of previously undetected diabetes mellitus.

Existing and emerging GLP-1 receptor agonist therapy: Ramifications for diabetic retinopathy screening.

GLP-1 receptor agonist treatment revolutionised the management of type 2 diabetes mellitus with significant enhancement of cardiovascular risk reduction. They have been instrumental in effectively managing the glycaemic control of this at-risk patient group. This class of drugs are associated with rapid improvement in glucose levels and consequently, transient early worsening of pre-existing diabetic retinopathy (DR) which is well-recognised, but this paradox is less commonly perceived in routine clinical practice. The recent shortage of supply has resulted in an enforced hiatus to prescribing all existing GLP-1 receptor agonists, which is expected to last all through 2024. This becomes even more pertinent as their DR could have progressed due to worsening HbA1c as a result of the unforeseen interruption to GLP-1 receptor agonist treatment. Therefore, when these medications are recommenced in a few months' time, all prescribers need to be aware of these patients' most up-to-date DR status and liaise with their affiliated screening service.

Comparative Study on Efficacy of Empagliflozin Versus Sitagliptin, as an Add-on Therapy to Metformin in Type 2 Diabetic Patients.

Introduction: More than 28.7 million individuals throughout the globe suffer from diabetes mellitus, with an estimated 11 percent of the population living with the condition in India. Changes in lifestyle and a variety of treatment plans are used in management. Metformin is a key drug for glycemic control, both when used alone and in combination. Our research compares the effectiveness of glycemic control achieved by empagliflozin plus sitagliptin. Methods: This study took place from November 2022 to April 2023 at the tertiary care hospital. The study did not begin until the ethical review was completed. There were two groups of patients, A and B. Everyone received a daily dose of Metformin 1,000 milligrams. Sitagliptin (50 mg twice daily) was administered to individuals in Group A, whereas Empagliflozin (10 mg once daily) was given to those in Group B. After three months of therapy, HbA1c was used to compare the two groups' levels of glycemic control to those at the start of treatment. To do this, we employed a proforma. Version 25 of the Statistical Package for the Social Sciences (SPSS Inc., Chicago, USA) was used for the analysis. Results: The average age of the 300 patients that participated in the trial was 42.33. There were 57.67% men and 42.33% females. "The mean reduction in HbA1c from baseline in Group A was -0.65 ± 0.11% and in Group B was -1.34 ± 0.13% with statistically significant P-value (P-value = 0.000)." Conclusion: The combination of Empagliflozin and Metformin is superior to that of Sitagliptin and Metformin for the maintenance of glycemic control.

Simplified integration of optimal self-management behaviors is associated with improved HbA1c in patients with type 1 diabetes.

PURPOSE: Living with type 1 diabetes requires burdensome and complex daily diabetes self-management behaviors. This study aimed to determine the association between integrated behavior performance and HbA1c, while identifying the behavior with the most significant impact on HbA1c. METHODS: A simple and feasible questionnaire was used to collect diabetes self-management behavior in patients with type 1 diabetes (n = 904). We assessed six dimensions of behavior performance: continuous glucose monitor (CGM) usage, frequent glucose testing, insulin pump usage, carbohydrate counting application, adjustment of insulin doses, and usage of apps for diabetes management. We evaluated the association between these behaviors and HbA1c. RESULTS: In total, 21.3% of patients performed none of the allotted behavior, while 28.5% of patients had a total behavior score of 3 or more. 63.6% of patients with a behavior score ≥ 3 achieved HbA1c goal, contrasting with only 30.4% of patients with a behavior score of 0-1. There was a mean 0.54% ± 0.05% decrease in HbA1c for each 1-unit increase in total behavior score after adjustment for age, family education and diabetes duration. Each behavior was independently correlated with a lower HbA1c level, with CGM having the most significant effect on HbA1c levels. CONCLUSIONS: Six optimal self-management behaviors, especially CGM usage, were associated with improved glycemic control, emphasizing the feasibility of implementing a simplified version of DSMES in the routine clinical care. REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03610984.

Associations Between HbA1c and Glucose Time in Range Using Continuous Glucose Monitoring in Type 1 Diabetes: Cross-Sectional Population-Based Study.

INTRODUCTION: Continuous glucose monitoring (CGM) introduces novel indicators of glycemic control. METHODS: This cross-sectional study, based on the Swedish National Diabetes Register, examines 27,980 adults with type 1 diabetes. It explores the relationships between HbA1c (glycated hemoglobin) and various CGM-derived metrics, including TIR (time in range, representing the percentage of time within the range of 4-10 mmol/l for 2 weeks), TAR (time above range), TBR (time below range), mean glucose, standard deviation (SD), and coefficient of variation (CV). Pearson correlation coefficients and linear regression models were utilized for estimation. RESULTS: The analysis included 46% women, 30% on insulin pump, 7% with previous coronary heart disease and 64% with retinopathy. Mean ± SD values were age 48 ± 18 years, diabetes duration 25 ± 16 years, HbA1c 58.8 ± 12.8 mmol/mol, TIR 58.8 ± 19.0%, TAR 36.3 ± 20.0%, TBR 4.7 ± 5.4%, mean sensor glucose 9.2 ± 2.0 mmol/l, SD 3.3 ± 1.0 mmol/l, and CV 36 ± 7%. The overall association between HbA1c and TIR was - 0.71 (Pearson's r), with R2 0.51 in crude linear regression and 0.57 in an adjusted model. R2 values between HbA1c and CGM mean glucose were 0.605 (unadjusted) 0.619 (adjusted) and TAR (unadjusted 0.554 and fully adjusted 0.568, respectively), while fully adjusted R2 values were 0.458, 0.175 and 0.101 between HbA1c and CGM SD, CGM CV and TBR, respectively. CONCLUSIONS: This descriptive study demonstrates that the degree of association between HbA1c and new and readily available CGM-derived metrics, i.e., time in range (TIR), time above range (TAR), and CGM mean glucose, is robust in assessing the management of individuals with type 1 diabetes in clinical settings. Metrics from CGM that pertain to variability and hypoglycemia exhibit only weak correlations with HbA1c.

Glycaemic Variability as a Predictor of Graft Failure following Infra-Inguinal Bypass for Peripheral Arterial Disease. A Retrospective Cohort Study.

BACKGROUND: Glycaemic variability (GV), measured as the change in visit-to-visit glycated haemoglobin (HbA1c), increases the risk of multiple adverse outcomes. However, the impact of GV on graft patency following infra-inguinal bypass (IIB) is unknown. A retrospective cohort study was undertaken to assess the impact of GV on graft patency. METHOD: A 3-year single centre retrospective case notes analysis of all people undergoing IIB between 2017-2019. Rutherford stage, graft conduit, level of bypass, procedure details, baseline demographics, co-morbidities, and GV were assessed. Time to re-intervention, ipsilateral amputation or death were recorded to determine primary patency (PP). RESULTS: 106 IIB outcomes were analysed: mean (±SD) age 68.0(9.2) years; 69(65.1%) male, 37(33.9%), 75(70.8%) had DM; 46(43.4.%) underwent elective procedures. GV>9.1% was associated with significantly lower median PP than GV<9.1%, 198 [97-753.5] vs. 713 [166.5-1044.5] days (p = 0.045). On univariate analysis, GV >9.1% vs <9.1% was significantly associated with PP (HR 1.85 [CI 1.091-3.136], p = 0.022). Bypass level was also a univariate predictor, with below knee bypasses (HR 2.31 [CI 1.164-4.564], p = 0.017), and tibial (HR 2.00 [CI 1.022-3.090], p <0.043) having lower PP than above knee bypasses. On multivariate adjustment, GV >9.1% and level of bypass remained independent predictors of primary patency, HR 1.96 (95% CI:1.12-3.42, p=0.018) and HR 2.54 (95%CI:1.24-5.22, p=0.011) respectively. CONCLUSIONS: GV is an independent predictor of primary patency following infra-inguinal bypass, thus optimising GV should be a therapeutic target.

Disparities in prevalence and treatment of diabetes, cardiovascular and chronic kidney diseases - Recommendations from the taskforce of the guideline workshop.

There is a mounting clinical, psychosocial, and socioeconomic burden worldwide as the prevalence of diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD) continues to rise. Despite the introduction of therapeutic interventions with demonstrated efficacy to prevent the development or progression of these common chronic diseases, many individuals have limited access to these innovations due to their race/ethnicity, and/or socioeconomic status (SES). However, practical guidance to providers and healthcare systems for addressing these disparities is often lacking. In this article, we review the prevalence and impact of healthcare disparities derived from the above-mentioned chronic conditions and present broad-based recommendations for improving access to quality care and health outcomes within the most vulnerable populations.

New-Onset Diabetes Mellitus after Kidney Transplantation.

New-Onset Diabetes Mellitus after Transplantation (NODAT) emerges as a prevalent complication post-kidney transplantation, with its incidence influenced by variations in NODAT definitions and follow-up periods. The condition's pathophysiology is marked by impaired insulin sensitivity and ß-cell dysfunction. Significant risk factors encompass age, gender, obesity, and genetics, among others, with the use of post-transplant immunosuppressants intensifying the condition. NODAT's significant impact on patient survival and graft durability underscores the need for its prevention, early detection, and treatment. This review addresses the complexities of managing NODAT, including the challenges posed by various immunosuppressive regimens crucial for transplant success yet harmful to glucose metabolism. It discusses management strategies involving adjustments in immunosuppressive protocols, lifestyle modifications, and pharmacological interventions to minimize diabetes risk while maintaining transplant longevity. The importance of early detection and proactive, personalized intervention strategies to modify NODAT's trajectory is also emphasized, advocating for a shift towards more anticipatory post-transplant care.

Effect of a two-only-meals-a-day and exercise lifestyle on HbA1c and anti-diabetic medication in a follow-up study of subjects with type 2 diabetes attending a free clinic in a north Maharashtra city.

Background: Type 2 Diabetes (T2D) is a global challenge with rising prevalence, inadequate compliance, and poor outcomes. Aims: Assess the effect of a 2-only-daily-meals with exercise lifestyle (2-OMEX) on (a) HbA1c, (b) anti-diabetic medication count (ADMC), (c) Kcal intakes, body weight, fasting insulin, and subjective well-being. Materials and Methods: This is a single-arm follow-up study conducted in a free 2-OMEX clinic in 2019-2020. Information for two meals and exercise compliance was obtained during the clinic visit. HbA1c was tested by HPLC and fasting insulin by the CLIA/CMIA method in private laboratories. Results: Eligible subjects (f = 49, m = 116) completing two or more visits and 60 days of follow-up had a mean age of 55.92 (10.43) years, a T2D duration of 8.20 (6.28) years, and a median observation period of 140 days. Statistically significant changes included HbA1c decline from 7.69 (1.70) to 7.00 (1.20) gm% (equivalent by the LogNormal method to 1.088 gm%), average weight loss at 5%(m), and 2%(f). ADMC declined from 2.32 to 2.14, the difference being significant with the WSR test (z = 2.0087, P = 0.0223). Subjects attaining anti-diabetic medication-free and normoglycemic status (HbA1c < 6.5 gm%) were 20 (12%). The number attaining HbA1c ≤ 7 gm%) significantly rose from 73 (44%) to 101 (61%) with an ADMC of 1.9 (chi-square = 9.531, df1, P = 0.0020203). Participants reported 'feeling energetic' (79%), feeling lighter (50%), and better sleep (35%). Average energy intakes dropped by 120 Kcal to 1580/day. Fasting insulin remained unchanged, from 12.61 (11.06) to 12.34 (11.78) mlU/L. The dropout rate was 35%. Conclusions: The 2-OMEX lifestyle showed a sizeable, favorable, and significant change in HbA1c, body weight, ADMC use in five months, and subjective benefits. Studies are necessary for remission impact and pathways.

Turning the tides: achieving rapid and safe glucose control in adolescents with suboptimally controlled type 1 diabetes using advanced hybrid closed loop systems.

Aim: Many adolescents with T1D experience a decline in metabolic control due to erratic eating habits and subpar adherence to treatment regimens. The objective of our retrospective observational study was to assess the effect of the Tandem Control IQ (CIQ) advanced hybrid closed-loop (AHCL) system on a cohort of adolescents with suboptimal glucose control. Methods: We retrospectively evaluated 20 non-adherent patients with T1D, who were inconsistently using Multiple Daily Injections (MDIs) and flash glucose monitoring and were subsequently started and on CIQ. Glucometrics and the Glucose Risk Index were assessed at baseline and after 2 weeks, 1 month, and 6 months of CIQ use. Results: The study included 20 adolescents with T1D (HbA1c: 10.0% ± 1.7). Time in range (TIR) increased from 27.1% ± 13.7 at baseline to 68.6% ± 14.2 at 2 weeks, 66.6% ± 10.7 at 1 month, and 60.4% ± 13.3 at 6 months of CIQ use. Time above range (TAR) >250 mg/dL decreased from 46.1% ± 23.8 to 9.9% ± 9.5 at 2 weeks, 10.8% ± 6.1 at 1 month, and 15.5% ± 10.5 at 6 months of AHCL use. Mean glucose levels improved from 251 mg/dL ± 68.9 to 175mg/dL ± 25.5 after 6 months of CIQ use. The Glucose Risk Index (GRI) also significantly reduced from 102 to 48 at 6 months of CIQ. HbA1c also improved from 10.0% ± 1.7 at baseline to 7.0% ± 0.7 after 6 months. Two patients experienced a single episode of mild diabetic ketoacidosis (DKA). Conclusions: AHCL systems provide a significant, rapid, and safe improvement in glucose control. This marks a pivotal advancement in technology that primarily benefited those who were already compliant.

The Current and Future Role of Insulin Therapy in the Management of Type 2 Diabetes: A Narrative Review.

Early initiation of intensive insulin therapy has been demonstrated to be effective in controlling glycemia and possibly preserving beta-cell function. Innovations in insulin formulations and delivery systems continue. However, we have seen an acceleration in the development of new classes of diabetes medications for individuals with type 2 diabetes and obesity, such as, for example, glucagon-like peptide-1 receptor agonists (GLP-1 RAs). These formulations have been shown to confer significant benefits in achieving good glycemic control with reduced hypoglycemia risk, weight loss, and cardiorenal protection. Therefore, it is reasonable to question whether there is still a role for insulin therapy in the management of type 2 diabetes. However, there are clear limitations inherent to GLP-1 RA therapy, including high rates of suboptimal adherence and treatment discontinuation due to high cost and side effects, which diminish long-term efficacy, and supply issues. In addition, newer formulations have shown improvements in convenience and tolerability, and have been shown to be even more effective when used in conjunction with basal insulin. In this narrative review, we discuss current evidence that supports GLP-1 RA use in combination with insulin therapy and the potential pitfalls of reliance on GLP-1 RAs as a substitute for insulin therapy.

Metabolic and Skeletal Characterization of the KK/Ay Mouse Model-A Polygenic Mutation Model of Obese Type 2 Diabetes.

Type 2 diabetes (T2D) increases fracture incidence and fracture-related mortality rates (KK.Cg-Ay/J. The Jackson Laboratory; Available from: https://www.jax.org/strain/002468 ). While numerous mouse models for T2D exist, few effectively stimulate persistent hyperglycemia in both sexes, and even fewer are suitable for bone studies. Commonly used models like db/db and ob/ob have altered leptin pathways, confounding bone-related findings since leptin regulates bone properties (Fajardo et al. in Journal of Bone and Mineral Research 29(5): 1025-1040, 2014). The Yellow Kuo Kondo (KK/Ay) mouse, a polygenic mutation model of T2D, is able to produce a consistent diabetic state in both sexes and addresses the lack of a suitable model of T2D for bone studies. The diabetic state of KK/Ay stems from a mutation in the agouti gene, responsible for coat color in mice. This mutation induces ectopic gene expression across various tissue types, resulting in diabetic mice with yellow fur coats (Moussa and Claycombe in Obesity Research 7(5): 506-514, 1999). Male and female KK/Ay mice exhibited persistent hyperglycemia, defining them as diabetic with blood glucose (BG) levels consistently exceeding 300 mg/dL. Notably, male control mice in this study were also diabetic, presenting a significant limitation. Nevertheless, male and female KK/Ay mice showed significantly elevated BG levels, HbA1c, and serum insulin concentration when compared to the non-diabetic female control mice. Early stages of T2D are characterized by hyperglycemia and hyperinsulinemia resulting from cellular insulin resistance, whereas later stages may feature hypoinsulinemia due to ß-cell apoptosis (Banday et al. Avicenna Journal of Medicine 10(04): 174-188, 2020 and Klein et al. Cell Metabolism 34(1): 11-20, 2022). The observed hyperglycemia, hyperinsulinemia, and the absence of differences in ß-cell mass suggest that KK/Ay mice in this study are modeling the earlier stages of T2D. While compromised bone microarchitecture was observed in this study, older KK/Ay mice, representing more advanced stages of T2D, might exhibit more pronounced skeletal manifestations. Compared to the control group, the femora of KK/Ay mice had higher cortical area and cortical thickness, and improved trabecular properties which would typically be indicative of greater bone strength. However, KK/Ay mice displayed lower cortical tissue mineral density in both sexes and increased cortical porosity in females. Fracture instability toughness of the femora was lower in KK/Ay mice overall compared to controls. These findings indicate that decreased mechanical integrity noted in the femora of KK/Ay mice was likely due to overall bone quality being compromised.

Effects of Two COVID-19 Lockdowns on HbA1c Levels in Patients with Type 1 Diabetes and Associations with Digital Treatment, Health Literacy, and Diabetes Self-Management: A Multicenter, Observational Cohort Study Over 3 Years.

INTRODUCTION: Short-term studies reported improved glycemic control and a decrease in eHbA1c (estimated hemoglobin A1c) in patients with type 1 diabetes during COVID-19 lockdown, but long-term changes are unknown. Therefore, the main objectives are to (1) analyze whether laboratory-measured HbA1c changed during and after two lockdowns and (2) investigate potential variables influencing HbA1c change. METHODS: In this cohort study, 291 adults with type 1 diabetes were followed over 3 years including the prepandemic phase and two lockdowns. The data from medical records and validated questionnaires assessing health literacy (HLS-EU-Q16), diabetes self-management (DSMQ-R27), general self-efficacy (GSE), and social support (F-SOZU-K14) were used to analyze associations with HbA1c levels (N = 2370) by performing multivariable linear regressions. RESULTS: The median age was 54 (38-63) years and 159 (54.6%) were male. All phases of the COVID-19 pandemic were associated with a significant increase in laboratory-measured HbA1c levels in percent (e.g., during first lockdown ß = 0.23, 95% confidence interval (CI) 0.07-0.39, p = 0.005; during the second lockdown, ß = 0.27, 95% CI 0.15-0.38, p < 0.001). HbA1c change during lockdowns was significantly affected by the number of checkups (ß = -0.03, 95% CI -0.05 to -0.01, p = 0.010), the value of HbA1c at previous observation (ß = 0.33, 95% CI 0.29-0.36, p < 0.001), educational level (secondary versus tertiary: ß = 0.22, 95% CI 0.06-0.38, p = 0.008; primary versus tertiary: ß = 0.31, 95% CI 0.10-0.52, p = 0.004), health literacy score (for each point: ß = -0.03, 95% CI -0.05 to - 0.002, p = 0.034), and diabetes self-management score (for each point: ß = -0.03, 95% CI -0.04 to -0.02, p < 0.001). The use of continuous glucose monitoring or insulin pump had no effect on HbA1c change. CONCLUSIONS: Lockdowns can lead to worsening glycemic control in patients with type 1 diabetes. Particularly patients with few check-ups, poor blood glucose values, deficits in diabetes self-management, low health literacy, and a low level of education seem to be at greater risk of worsening glycemic control during lockdowns and, therefore, require special medical care, e.g., through telemedicine. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04821921.

Real-World Effectiveness of the Gla-300 + Cap + App Program in Adult Users Living with Type 2 Diabetes in Taiwan.

INTRODUCTION: Health2Sync (H2S) is a digital health technology platform that provides coaching and titration support to patients with diabetes. The Mallya cap converts a conventional insulin pen into a smart connected device that can automatically synchronize dose values and associated timestamps (upon injection) to the H2S platform. This single-arm real-world study evaluated the effectiveness of insulin glargine 300 U/mL (Gla-300) combined with H2S and Mallya cap (Gla-300 + Cap + App program) on clinical outcomes among users with type 2 diabetes (T2D) in Taiwan. METHODS: Adults (aged ≥ 20 years) with T2D who were registered H2S users and initiated Mallya cap for a new/existing Gla-300 regimen (identification period May 1, 2021-May 31, 2022) were included in this retrospective cohort study. Follow-up data from H2S were collected for 90 days. Glycated hemoglobin (HbA1c) change (baseline to follow-up) and HbA1c goal attainment were primary outcomes. Hypoglycemia incidence and usage metrics of Mallya cap were secondary outcomes. RESULTS: Of 83 participants, 38.6% were new Gla-300 users. HbA1c was reduced in both new (- 2.4 [2.7] %, - 26.2 [29.5] mmol/mol) and previous Gla-300 users (- 0.5 [1.6] %, - 5.5 [17.5] mmol/mol). Reduction in HbA1c was significant (p < 0.05) in both groups. At follow-up, 43.4% of users had a reduction of > 0.5%. Mean HbA1c reductions increased numerically with higher baseline HbA1c and with longer duration of Mallya cap usage. CONCLUSIONS: Use of digital technology within a connected ecosystem such as Gla-300 + Cap + App program could help people with type 2 diabetes to improve their glycemic condition.

Using nephropathy as an outcome to determine the HbA1c diagnostic threshold for type 2 diabetes.

OBJECTIVE: The hemoglobin A1c (HbA1c) diagnostic threshold for type 2 diabetes (T2D) of 6.5 % (48 mmol/mol) was based on the prevalence of retinopathy found in populations not known to have T2D. It is unclear if nephropathy has a similar HbA1c threshold, partly because it is a rarer complication of early diabetes. This cohort study investigated a very high diabetes prevalence population to determine if a better diagnostic HbA1c value can be established for predicting nephropathy rather than retinopathy in subjects without T2D. METHODS: The urine albumin:creatinine ratios (UACRs) of 2920 healthy individuals from the Qatar Biobank who had an HbA1c ≥ 5.6 %. were studied. Nephropathy was defined as a UACR≥30 mg/g and its prediction by HbA1c was assessed using cut-points ranging from 5.7 to 7.0 % to dichotomize high from low HbA1c. RESULTS: Although there was a significant trend for an increased prevalence of abnormal UACR as the HbA1c threshold increased (p < 0.01), significance was due mostly to subjects with HbA1c ≥ 7.0 % (53 mmol/mol). The odds ratios for abnormal UACR were similar over the 5.7-6.9 % HbA1c threshold range, with a narrow odds ratio range of 1.2-1.6. Utilizing area-under-receiver-operating characteristic curves, no HbA1c threshold <7.0 % was identified as the best predictor of nephropathy. CONCLUSION: Even in a population with a high prevalence of known and unknown diabetes, no HbA1c threshold <7.0 % could be found predicting an increased prevalence of nephropathy. This means there is not a requirement to change the existing retinopathy-based HbA1c threshold of 6.5 % to also accommodate diabetes nephropathy risk.

Association of Hypomagnesemia With Diabetic Complications.

OBJECTIVE: The study aimed to study the association of hypomagnesemia with diabetic complications in type 2 diabetics. MATERIALS AND METHOD: This cross-sectional study, conducted at a Ghurki Trust Teaching Hospital, spanned from January to June 2023 and included 100 randomly selected diabetic patients aged 30-70. With institutional board approval and informed consent, the study focused on assessing hypomagnesemia, using a standard level of below 1.6 mg/dL, ensuring participant confidentiality and privacy. Data collected through physical assessments were analyzed using IBM SPSS Statistics for Windows, Version 24.0 (Released 2016; IBM Corp., Armonk, New York, United States), including descriptive statistics, analysis of variance (ANOVA), and paired t-test. RESULTS: A total of 100 diabetic admitted patients were randomly selected for the study ages from 30 to 70 years irrespective of their gender. The mean age of the participants was 53.86±9.74 years. The mean HbA1c of the participants was 8.7±2.32. Forty-eight percent of them had HbA1c less than 8, while 52% had greater than 8 HbA1c. The mean HbA1c in the hypomagnesemia group was 10.8±1.98, while in the normomagnesemia group, it was 8.9±2.2. There were 58.97% of foot ulcers in Group 1, while in Group 2, there were 31.14%. Around 38.46% and 14.75% had neuropathy in Groups 1 and 2, respectively. Nephropathy in Group 1 was 28.20%, while in Group 2, it was 11.47%. Around 69.23% of Group 1 had retinopathy and 37.70% had retinopathy in Group 2. Hypertension was 23.07% in Group 1 and 37.70% in Group 2; moreover, 7.69% and 8.19% had coronary diseases in Groups 1 and 2 accordingly. CONCLUSION:  The current study concluded that hypomagnesemia was found to have an association with diabetic complications like neuropathy, nephropathy, foot ulcers, and poor glycemic control as evidenced by HbA1c.