Impact of sustained virologic response on glucose parameters among patients with chronic hepatitis C treated with direct-acting antivirals.

Objective: The aim of this study was to evaluate the glycated hemoglobin (HbA1c) levels before and after sustained virologic response (SVR) and investigate the baseline characteristics associated with improved glycemic control in patients with chronic hepatitis C (CHC) achieving SVR after directacting antivirals (DAA) therapy. Materials and methods: Consecutive adult patients with CHC who achieved SVR after DAA treatment between January 2016 and December 2017 at Hospital de Clínicas de Porto Alegre (RS, Brazil) were prospectively included. Levels of HbA1c were measured up to 24 weeks before DAA therapy and 12 weeks after SVR. Exclusion criteria were decompensated cirrhosis, HIV and/or hepatitis B virus, liver disease of other etiologies, and/or modification of prediabetes/ type 2 diabetes mellitus (PDM/T2DM) management. The primary outcome was a comparison of HbA1c levels before and after SVR. Secondary outcomes were the baseline variables associated with improved glycemic control. Results: The study included 207 patients with a mean age of 60.6±10.7 years, of whom 51.7% were women, 56% had cirrhosis, 37.7% had HCV genotype 3, and 54.5% had baseline T2DM or PDM. The median HbA1c level reduced significantly after SVR (5.5%, interquartile range [IQR] 4.9%-6.3%) compared with baseline (5.7%, IQR 5.3%-6.7%; p = 0.01). The baseline characteristics associated with improved HbA1c after SVR were cirrhosis, genotype 3, and age ≤ 60 years. Conclusion: Among patients with CHC, SVR after DAA was associated with HbA1c reduction, particularly in those with cirrhosis, genotype 3, and age ≤ 60 years.

Development of a clinical calculator to aid the identification of MODY in pediatric patients at the time of diabetes diagnosis.

Maturity Onset Diabetes of the Young (MODY) is a young-onset, monogenic form of diabetes without needing insulin treatment. Diagnostic testing is expensive. To aid decisions on who to test, we aimed to develop a MODY probability calculator for paediatric cases at the time of diabetes diagnosis, when the existing "MODY calculator" cannot be used. Firth logistic regression models were developed on data from 3541 paediatric patients from the Swedish 'Better Diabetes Diagnosis' (BDD) population study (n = 46 (1.3%) MODY (HNF1A, HNF4A, GCK)). Model performance was compared to using islet autoantibody testing. HbA1c, parent with diabetes, and absence of polyuria were significant independent predictors of MODY. The model showed excellent discrimination (c-statistic = 0.963) and calibrated well (Brier score = 0.01). MODY probability > 1.3% (ie. above background prevalence) had similar performance to being negative for all 3 antibodies (positive predictive value (PPV) = 10% v 11% respectively i.e. ~ 1 in 10 positive test rate). Probability > 1.3% and negative for 3 islet autoantibodies narrowed down to 4% of the cohort, and detected 96% of MODY cases (PPV = 31%). This MODY calculator for paediatric patients at time of diabetes diagnosis will help target genetic testing to those most likely to benefit, to get the right diagnosis.

SGLT1 and SGLT2 inhibition, circulating metabolites, and cerebral small vessel disease: a mediation Mendelian Randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) and SGLT1 inhibitors may have additional beneficial metabolic effects on circulating metabolites beyond glucose regulation, which could contribute to a reduction in the burden of cerebral small vessel disease (CSVD). Accordingly, we used Mendelian Randomization (MR) to examine the role of circulating metabolites in mediating SGLT2 and SGLT1 inhibition in CSVD. METHODS: Genetic instruments for SGLT1/2 inhibition were identified as genetic variants, which were both associated with the expression of encoding genes of SGLT1/2 inhibitors and glycated hemoglobin A1c (HbA1c) level. A two-sample two-step MR was used to determine the causal effects of SGLT1/2 inhibition on CSVD manifestations and the mediating effects of 1400 circulating metabolites linking SGLT1/2 inhibition with CSVD manifestations. RESULTS: A lower risk of deep cerebral microbleeds (CMBs) and small vessel stroke (SVS) was linked to genetically predicted SGLT2 inhibition. Better white matter structure integrity was also achieved, as evidenced by decreased mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), as well as lower deep (DWMH) and periventrivular white matter hyperintensity (PWMH) volume. Inhibiting SGLT2 could also lessen the incidence of severe enlarged perivascular spaces (EPVS) located at white matter, basal ganglia (BG) and hippocampus (HIP). SGLT1 inhibition could preserve white matter integrity, shown as decreased MD of white matter and DWMH volume. The effect of SGLT2 inhibition on SVS and MD of white matter through the concentration of 4-acetamidobutanoate and the cholesterol to oleoyl-linoleoyl-glycerol (18:1 to 18:2) ratio, with a mediated proportion of 30.3% and 35.5% of the total effect, respectively. CONCLUSIONS: SGLT2 and SGLT1 inhibition play protective roles in CSVD development. The SGLT2 inhibition could lower the risk of SVS and improve the integrity of white matter microstructure via modulating the level of 4-acetamidobutanoate and cholesterol metabolism. Further mechanistic and clinical studies research are needed to validate our findings.

Influence of early use of sodium-glucose transport protein 2 inhibitors, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on the legacy effect of hyperglycemia.

Background: A phenomenon known as legacy effect was observed that poor glycemic control at early stage of patients with newly-diagnosed type 2 diabetes (T2D) increases the risk of subsequent cardiovascular diseases (CVD). Early use of some novel anti-hyperglycemic agents, such as sodium-glucose transport protein 2 inhibitors (SGLT-2i), may attenuate this effect, but the evidence is limited. Methods: Two retrospective cohorts of newly diagnosed T2D patients from 2010-2023 were assembled using the Yinzhou Regional Health Care Database (YRHCD) with different definitions of the early exposure period - the 1-year exposure cohort and 2-year exposure cohort, which were comprised of subjects who had HbA1c measurement data within 1 year and 2 years after their T2D diagnosis, respectively. Using Cox proportional hazards models, we examined the association between high HbA1c level (HbA1c>7%) during the early exposure period and the risk of subsequent CVD. This analysis was performed in the overall cohort and three subpopulations with different treatments during the early exposure period, including patients initiating SGLT-2i or glucagon-like peptide-1 receptor agonists (GLP-1RA), patients using dipeptidyl peptidase-4 inhibitors (DPP-4i), and patients without using SGLT-2i, GLP-1RA, and DPP-4i. Besides, subgroup analyses were performed by stratifying patients into age <55 and ≥55 years. Results: A total of 21,477 and 22,493 patients with newly diagnosed T2D were included in the two final cohorts. Compared with patients with mean HbA1c ≤ 7% during the early exposure period, those with HbA1c>7% had higher risks of incident CVD, with a HR of 1.165 (95%CI, 1.056-1.285) and 1.143 (95%CI, 1.044-1.252) in 1-year and 2-year exposure period cohort. Compared to non-users, in patients initiating SGLT-2i/GLP-1RA within 1 or 2 years after T2D diagnosis, higher HbA1c level at baseline was not associated with CVD in both two cohorts. In subgroup analyses, results were generally consistent with the main analysis. Conclusions: Poor glycemic control in the early stage of T2D increased later CVD risk in Chinese adults with newly diagnosed T2D. Compared to non-users, this association was smaller and non-significant in patients receiving SGLT-2i/GLP-1RA during the early stage of T2D, indicating early use of these drugs may have the potential to mitigate legacy effects of hyperglycemia.

Etiologies underlying subtypes of long-standing type 2 diabetes.

BACKGROUND: Attempts to subtype, type 2 diabetes (T2D) have mostly focused on newly diagnosed European patients. In this study, our aim was to subtype T2D in a non-white Emirati ethnic population with long-standing disease, using unsupervised soft clustering, based on etiological determinants. METHODS: The Auto Cluster model in the IBM SPSS Modeler was used to cluster data from 348 Emirati patients with long-standing T2D. Five predictor variables (fasting blood glucose (FBG), fasting serum insulin (FSI), body mass index (BMI), hemoglobin A1c (HbA1c) and age at diagnosis) were used to determine the appropriate number of clusters and their clinical characteristics. Multinomial logistic regression was used to validate clustering results. RESULTS: Five clusters were identified; the first four matched Ahlqvist et al subgroups: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and a fifth new subtype of mild early onset diabetes (MEOD). The Modeler algorithm allows for soft assignments, in which a data point can be assigned to multiple clusters with different probabilities. There were 151 patients (43%) with membership in cluster peaks with no overlap. The remaining 197 patients (57%) showed extensive overlap between clusters at the base of distributions. CONCLUSIONS: Despite the complex picture of long-standing T2D with comorbidities and complications, our study demonstrates the feasibility of identifying subtypes and their underlying causes. While clustering provides valuable insights into the architecture of T2D subtypes, its application to individual patient management would remain limited due to overlapping characteristics. Therefore, integrating simplified, personalized metabolic profiles with clustering holds greater promise for guiding clinical decisions than subtyping alone.

ANALYSIS OF ANTIDIABETIC THERAPY FOR TYPE 2 DIABETES IN PRIMARY HEALTH CARE (WESTERN KAZAKHSTAN).

Diabetes Mellitus Type 2 (T2D) represents a significant global health challenge, with increasing prevalence and the need for effective management strategies. Despite the widespread nature of the disease, there is disagreement regarding the optimal glycemic targets for patients with Type 2 diabetes. The American Diabetes Association recommends aiming for an HbA1C level of less than 7% (53 mmol/mol). About 50% of diabetes patients do not meet their glycemic targets, leading to an increased risk of chronic complications associated with diabetes. Although lifestyle modifications are crucial for prevention and management, most T2D patients eventually need pharmacotherapy to maintain control over their blood glucose levels. In Western Kazakhstan, a study was conducted to evaluate the efficacy of antidiabetic therapy in primary healthcare settings. Aim - to assess the proportion of patients with uncontrolled glycemia among adult patients with T2D, and to analyze antidiabetic therapy in the primary health care (Western Kazakhstan). The cross-sectional study involved 96 participants, divided into two groups based on their HbA1c levels: 32 patients with an HbA1c <7%; 64 patients with an HbA1c >7%. In the study 58 patients (60,6%) were female and 38 patients (39,4%) were male. Data analysis was performed using IBM SPSS 26 and GraphPad, employing Kolmogorov-Smirnov and Shapiro-Wilk tests for distribution, medians and interquartile ranges for non-normal variables, Chi-squared and Fisher's Exact tests for nominal variables, and representation of nominal data in absolute and percentage values. The study found that 66.67±5.89% of participants had unsatisfactory glycemic control at enrollment, with only 33.33±8.33% achieving the desired HbA1c level of <7% (p<=0.005; t=3.26). Statistical analysis showed a significant association between higher glucose levels and the type of therapy, with insulin therapy more common in patients with glucose levels >7 (χ²=5.500, df = 1, p <0.05) and a similar correlation with SGLT-2 inhibitors (Fisher's Exact Test, p<0.01). Analysis of the data collected from urban polyclinics in Aktobe highlighted a troubling fact: two-thirds of the participants (66.67%) had unsatisfactory glycemic control. This is considerably lower than the 45% to 60% control rates reported internationally, indicating an area for significant improvement in the regional management of T2D. The study underscores the importance of a tailored therapeutic approach, balancing drug efficacy, patient response, and individual healthcare needs. Higher variability and blood sugar peaks were observed in patients with HbA1c levels above 7%. In the Western region of Kazakhstan, metformin was the most commonly prescribed antidiabetic drug, consistent with its first-line therapy status. Patients with HbA1c >7% were more likely to receive insulin therapy and SGLT-2 inhibitors, indicating their role in more intensive treatment strategies. Less use of incretins and sulfonylureas was noted among patients with HbA1c <7%, possibly due to their efficacy, safety profiles, or availability of newer alternatives. The findings call for enhanced strategies to improve diabetes management and increase the percentage of patients achieving their glycemic targets, aiming for a more personalized, patient-centered care model in Kazakhstan and potentially similar healthcare settings.

Hyperglycaemia in people with diabetes and chronic kidney disease.

Assessment and treatment of hyperglycaemia in people with diabetes and chronic kidney disease (CKD) are challenging. In advanced CKD HbA1c can be unreliable, and treatment adjustments should be supported by other glucose measurements (e.g., continuous glucose monitoring (CGM) or blood glucose measurements). Glucose-lowering treatments should be evaluated based on CKD and an individualised assessment of risk factors especially hypoglycaemia. This review aims at providing an overview of the options for glycaemic monitoring and glucose-lowering treatments in people with diabetes and CKD.

The impact of major depressive disorder on glycaemic control in type 2 diabetes: a longitudinal cohort study using UK Biobank primary care records.

BACKGROUND: This study evaluates longitudinal associations between glycaemic control, measured by mean and within-patient variability of glycated haemaglobin (HbA1c) levels, and major depressive disorder (MDD) in individuals with type 2 diabetes (T2D), focusing on the timings of these diagnoses. METHODS: In UK Biobank, T2D was defined using self-report and linked health outcome data, then validated using polygenic scores. Repeated HbA1c measurements (mmol/mol) over the 10 years following T2D diagnosis were outcomes in mixed effects models, with disease duration included using restricted cubic splines. Four MDD exposures were considered: MDD diagnosis prior to T2D diagnosis (pre-T2D MDD), time between pre-T2D MDD diagnosis and T2D, new MDD diagnosis during follow-up (post-T2D MDD) and time since post-T2D MDD diagnosis. Models with and without covariate adjustment were considered. RESULTS: T2D diagnostic criteria were robustly associated with T2D polygenic scores. In 11,837 T2D cases (6.9 years median follow-up), pre-T2D MDD was associated with a 0.92 increase in HbA1c (95% CI: [0.00, 1.84]), but earlier pre-T2D MDD diagnosis correlated with lower HbA1c. These pre-T2D MDD effects became non-significant after covariate adjustment. Post-T2D MDD individuals demonstrated increasing HbA1c with years since MDD diagnosis ( ß = 0.51 , 95% CI: [0.17, 0.86]). Retrospectively, across study follow-up, within-patient variability in HbA1c was 1.16 (95% CI: 1.13-1.19) times higher in post-T2D MDD individuals. CONCLUSIONS: The timing of MDD diagnosis is important for understanding glycaemic control in T2D. Poorer control was observed in MDD diagnosed post-T2D, highlighting the importance of depression screening in T2D, and closer monitoring for individuals who develop MDD after T2D.

Evaluating the efficacy and safety of empagliflozin addition to insulin and oral antidiabetic medication (OAD) regimen in poorly controlled type 2 diabetes and obese patients.

Insulin resistance complicates diabetes care. Its effectiveness and tolerability as an addition to metformin, DPP4 inhibitor and insulin treatment in type 2 diabetic patients will be examined in this research. Participants with type 2 diabetes from poor socio-economic backgrounds had HbA1c values ≥8.5% when using Insulin+Metformin+DPP-4 inhibitors. They received 10mg Empagliflozin daily for 12 weeks (n=143). The main outcome was change in HbA1c at 12th week from baseline. Secondary outcomes were baseline weight and week 12 FPG. Adjusted mean (SE) HbA1c increases at week 12 were: Mean ± SD 10.38 (6.8-17.0) vs. Mean±SD 9.05±1.77 (5.60-16.0) with empagliflozin 10mg. When added to the regimen, empagliflozin significantly reduced FPG, systolic and diastolic blood pressure. The mean (SE) BMI increases from baseline were 31.28±5.89 (16.0-66.0) and 29.73±5.47 (3.0-46.0) with 10mg empagliflozin. Two individuals experienced urinary tract infections as AEs, but no genital infections. Adding empagliflozin 10mg daily to metformin+DPP4 inhibitor+insulin improved glycemic control, body weight and blood pressure for 12 weeks. The intervention was well-tolerated, highlighting empagliflozin's therapeutic potential.

Severe dawn phenomenon predicts long-term risk of all-cause mortality in patients with type 2 diabetes.

AIMS: The dawn phenomenon (DP) is an abnormal early morning blood glucose rise without nocturnal hypoglycaemia, which can be more easily and precisely assessed with continuous glucose monitoring (CGM). This prospective study aimed to explore the association between DP and the risk of all-cause mortality in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 5542 adult inpatients with type 2 diabetes in a single centre were analysed. The magnitude of DP (ΔG) was defined as the increment in the CGM-determined glucose value from nocturnal nadir (after 24:00) to prebreakfast. Participants were stratified into four groups by ΔG: ≤1.11, 1.12-3.33, 3.34-5.55, and >5.55 mmol/L. Cox proportional hazard regression models were used to evaluate the impact of DP on all-cause mortality risk. RESULTS: During a median follow-up of 9.4 years, 1083 deaths were identified. The restricted cubic spline revealed a nonlinear (p for nonlinearity = 0.002) relationship between ΔG and the risk of all-cause mortality. A multivariate-adjusted Cox regression model including glycated haemoglobin A1c (HbA1c) showed that ΔG > 5.55 mmol/L was associated with 30% (95% CI, 1.01-1.66) higher risk of all-cause mortality, as compared with ΔG 1.12-3.33 mmol/L. CONCLUSIONS: Higher ΔG is significantly related to an increased risk of all-cause mortality in type 2 diabetes, suggesting that severe DP should be given more attention as a part of glucose management to reduce the risk of long-term adverse outcomes.

HbA1c changes in a deprived population who followed or not a diabetes self-management programme, organised in a multi-professional primary care practice: a historical cohort study on 207 patients between 2017 and 2019.

BACKGROUND: Diabetes self-management (DSM) helps people with diabetes to become actors in their disease. Deprived populations are particularly affected by diabetes and are less likely to have access to these programmes. DSM implementation in primary care, particularly in a multi-professional primary care practice (MPCP), is a valuable strategy to promote care access for these populations. In Rennes (Western France), a DSM programme was designed by a MPCP in a socio-economically deprived area. The study objective was to compare diabetes control in people who followed or not this DSM programme. METHOD: The historical cohort of patients who participated in the DSM programme at the MPCP between 2017 and 2019 (n = 69) was compared with patients who did not participate in the programme, matched on sex, age, diabetes type and place of the general practitioner's practice (n = 138). The primary outcome was glycated haemoglobin (HbA1c) change between 12 months before and 12 months after the DSM programme. Secondary outcomes included modifications in diabetes treatment, body mass index, blood pressure, dyslipidaemia, presence of microalbuminuria, and diabetes retinopathy screening participation. RESULTS: HbA1c was significantly improved in the exposed group after the programme (p < 0.01). The analysis did not find any significant between-group difference in socio-demographic data, medical history, comorbidities, and treatment adaptation. CONCLUSIONS: These results, consistent with the international literature, promote the development of DSM programmes in primary care settings in deprived areas. The results of this real-life study need to be confirmed on the long-term and in different contexts (rural area, healthcare organisation).

Association of prediabetes with clinical outcomes in patients with chronic coronary syndrome: a post hoc analysis of the ISCHEMIA and ISCHEMIA-CKD trials.

BACKGROUND: There is conflicting evidence whether prediabetes is associated with adverse clinical outcomes in patients with chronic coronary syndrome. We aimed to assess the effect of prediabetes in patients with chronic coronary syndrome on clinical outcomes. METHODS: This is a secondary analysis of data from the ISCHEMIA and ISCHEMIA-CKD trials, including patients with chronic coronary syndrome determined by coronary computed tomography angiography or exercise-stress testing. Participants were assigned to the normoglycemia group (HbA1c < 5.7% [< 39 mmol/mol]), prediabetes group (HbA1c 5.7-6.4% [40-47 mmol/mol]), or diabetes group (HbA1c ≥ 6.5% [≥ 48 mmol/mol]). The primary end point of this study was all-cause mortality. Secondary endpoints included major adverse cardiovascular events and composites thereof. RESULTS: Overall, the primary endpoint all-cause mortality occurred in 330 (8.4%) of 3910 patients over a median follow-up time of 3.1 years (IQR 2.1-4.1). The primary endpoint all-cause mortality occurred in 37 (5.2%) of 716 patients in the normoglycemia group, in 63 (6.9%) of 911 in the prediabetes group, and in 230 (10.1%) of 2283 in the diabetes group. In the covariate-adjusted Cox model analysis, the estimated adjusted HR (aHR) in the prediabetes group as compared with the normoglycemia group was 1.45 (95%CI, 0.95-2.20). The aHR in the diabetes group as compared with the normoglycemia group was 1.84 (95%CI, 1.29-2.65). Prediabetes, compared with normoglycemia, was associated with an increased risk of stroke (aHR, 3.44, 95%CI, 1.15-10.25). Subgroup analyses suggested an increased risk of all-cause death associated with prediabetes in males and patients under 65 years. CONCLUSIONS: In patients with chronic coronary syndrome, diabetes but not prediabetes was associated with significantly increased risk of all-cause death within a median follow-up period of 3.1 years. Trial Registration NCT01471522, BioLINCC ID 13936.

Effectiveness of structured exercise program on insulin resistance and quality of life in type 2 diabetes mellitus-A randomized controlled trial.

OBJECTIVE: Impaired glucose control & Insulin resistance are reported to be risk factors for the development of cardiovascular diseases. To find the effects of a structured exercise program on insulin resistance, glycaemic control, functional capacity, and quality of life in patients with Type 2 diabetes mellitus. DESIGN: Randomized, controlled trial. SETTING: Diabetic Foot Clinic, Department of Physiotherapy & Department of General Medicine, Kasturba Hospital in Manipal, Karnataka, India. PARTICIPANTS: 160 participants aged between 30-65 years with Type 2 diabetes mellitus. INTERVENTION: A set of structured exercise programs (aerobic, resistance, and combined) along with the standard hospital care was performed 3-5 times weekly for 12 weeks. MEASUREMENTS: PRIMARY OUTCOME MEASURES: Fasting Insulin Level, Homa-IR, Six-minute walk test (6MWT), and WHOQOL-BREF questionnaire at baseline and 12th week. SECONDARY OUTCOME MEASURES: Body composition analysis, Fasting Blood Sugar, Postprandial Blood Sugar, Glycated Haemoglobin (HbA1c), and GPAQ questionnaire at baseline and 12th week. RESULTS: Significant differences have been observed in Homeostasis model assessment for insulin resistance (Homa-IR) (F (1, 144) = 89.29, p < 0.001); Fasting insulin (FI) (F (1, 144) = 129.10, p < 0.001); Fasting blood sugar (FBS) (F (1, 144) = 12.193, p< 0.001); Post prandial blood sugar (PPBS) (F (1, 144) = 53.015, p< 0.001); glycated haemoglobin (HbA1c) (F (1, 144) = 80.050, p < 0.001); WHOQOL-Physical health (F (1, 144) = 20.008, p< 0.001), Psychological (F (1, 144) = 77.984, p< 0.001), Social relationship (F (1, 144) = 44.866, p< 0.001); Environmental (F (1, 144) = 69.974, p< 0.001); Six minute walk test (6MWT) (F (1, 144) = 84.135, p< 0.001) in the study group when compared with the control group from baseline to 12th week. CONCLUSIONS: The study reveals that a 12-week structured exercise training program effectively reduces insulin resistance, improves quality of life, enhances functional capacity, and improves glycaemic control in type 2 diabetes mellitus.

Ultra rapid lispro improves postprandial glucose control versus lispro in combination with basal insulin: a study based on CGM in type 2 diabetes in China.

Aim: To evaluate the efficacy and safety of URLi (ultra rapid lispro insulin) compared to insulin lispro as bolus insulin with basal insulin using CGM in the individuals with type 2 diabetes(T2D) in China. Methods: This was a double-blind, randomized, parallel, prospective, phase 3 study. Subjects with uncontrolled T2D were recruited and randomized 1:2 into the insulin lispro and URLi groups. Subjects received a consistent basal insulin regimen during the study and self-administered insulin lispro or URLi before each meal throughout the treatment period. Subjects underwent a 3-day continuous glucose monitoring (CGM) at the baseline and endpoint respectively, and then CGM data were analyzed. The primary endpoint was to compare the difference in postprandial glucose (PPG) control using CGM between the two groups. Results: A total of 57 subjects with T2D completed the study. Our CGM data showed that postprandial glucose excursions after breakfast (BPPGE) in the URLi group was lower than that in the insulin lispro group (1.59 ± 1.57 mmol/L vs 2.51 ± 1.73 mmol/L, p = 0.046). 1-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.37 ± 3.28 mmol/L vs 0.24 ± 2.58 mmol/L, p = 0.047). 2-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.12 ± 4.00 mmol/L vs 1.22 ± 2.90 mmol/L, p = 0.021). The mean HbA1c level decreased by 1.1% in the URLi group and 0.99% in the insulin lispro group, with no treatment difference (p = 0.642). In the CGM profile, TBR was not significantly different between the two groups (p = 0.743). The weight gain also did not differ between the two groups (p = 0.303). Conclusion: URLi can control breakfast PPG better than insulin lispro in adults with T2D in China, while it is non-inferior in improving HbA1c. The incidence of hypoglycemic and weight gain were similar between the two groups.

Measuring the effectiveness of hybrid diabetes care over 90 days through continuous data monitoring in type 2 diabetic patients.

Background: Diabetes Mellitus, a global health challenge, affects 537 million individuals. Traditional management relies on periodic clinic visits, but technological advancements, including remote monitoring, offer transformative changes. Telemedicine enhances access, convenience, adherence, and glycemic control. Challenges include trust-building and limitations in face-to-face interactions. Integrating remote monitoring with in-person healthcare creates a hybrid approach. This study evaluates the impact on Type 2 Diabetes patients over 3 months. Methods: A retrospective case-control observational study. Inclusion criteria involved previous Type 2 Diabetes diagnosis and a minimum 3-month GluCare model period with two physical visits. Patients in the case group had in-clinic visits, bi-weekly app engagement, and monthly body weight readings. Control group had in-clinic visits only. Outcomes measured included HbA1c, lipid profile, CV risk, eGFR, urine Albumin/Creatinine Ratio, Uric Acid, and CRP. Results: Case group showed significant HbA1c improvements (-2.19%), especially in higher baseline levels. Weight, BMI, LDL, total cholesterol, and CVD risk also improved. Controls showed smaller improvements. Higher digital interactions correlated with better outcomes. Patients with ≥11 interactions showed significant reductions in HbA1c (-2.38%) and weight (-6.00 kg). Conclusion: The GluCare.Health hybrid model demonstrates promising outcomes in Type 2 diabetes management. The integration of in-clinic consultations with continuous remote monitoring leads to substantial improvements in glycemic control and clinical parameters. The study highlights the importance of patient engagement in achieving positive outcomes, with higher digital interactions associated with greater reductions in HbA1c and weight. The hybrid approach proves more effective than digital-only interventions, emphasizing the need for comprehensive, end-to-end solutions in diabetes care.

Effects of Lactobacillus plantarum supplementation on glucose and lipid metabolism in type 2 diabetes mellitus and prediabetes: A systematic review and meta-analysis of randomized controlled trials.

Lactobacillus plantarum has been shown to improve glucose and lipid metabolism in mouse models of type 2 diabetes mellitus (T2DM). However, it remains unclear whether such benefits extend to humans. A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to clarify the effect of L. plantarum supplementation on glucose and lipid metabolism in T2DM and prediabetes. The PubMed, Cochrane, and Web of Science databases were searched. A random-effects model was used to estimate the pooled mean difference with 95% CI (confidence interval). L. plantarum supplementation reduced the levels of fasting plasma glucose (-0.41, 95%CI -0.63, -0.19 mg/dL; n = 5) and hemoglobin A1c (-0.2, 95%CI: -0.3, 0%; n = 4). A non-statistically significant tendency towards improvements in the Homeostatic Model Assessment for Insulin Resistance (MD: -0.74, 95%CI: -1.72, 0.25; n = 3), low-density lipoprotein cholesterol (-6.87; 95%CI: -15.03, 1.29 mg/dL; n = 3), high-density lipoprotein cholesterol (MD: 1.34; 95%CI: -0.78, 3.46 mg/dL; n = 3), triglyceride (MD: -3.90; 95%CI: -11.05, 3.24 mg/dL; n = 3), and total cholesterol (MD: -4.88; 95%CI: -11.84, 2.07 mg/dL; n = 3) was observed with the supplementation. In summary, while the evidence from the currently available RCTs provides a crude indication that L. plantarum supplementation might improve glucose and lipid metabolism in patients with T2DM and prediabetes, the benefits of the supplementation are likely subtle, and its clinical significance requires further investigation.

Triglyceride-glucose index: A surrogate marker of homeostasis model assessment of insulin resistance to predict diabetic nephropathy.

Objectives: To determine the association of triglyceride-glucose index with homeostasis model assessment of insulin resistance in type 2 diabetes mellitus patients, and to determine the association of triglyceride-glucose index with urinary albumin-to-creatinine ratio for predicting diabetic nephropathy. METHODS: The observational, cross-sectional study was conducted from September 2021 to September 2022 at the Department of Chemical Pathology, Pakistan Railway Hospital, Rawalpindi, Pakistan and comprised recently-diagnosed type 2 diabetes mellitus patients. Recorded data included age, gender, vitals, diabetes duration, body mass index and other pertinent demographic and clinical information. Measurements included spot urine albumin-to-creatinine ratio, triglycerideglucose index, homeostasis model assesment of insulin resistance as well as fasting serum insulin, fasting plasma glucose, glycosylated haemoglobin, triglycerides, total cholesterol and serum creatinine. On the basis of triglyceride-glucose index scores, the participants were divided into 4 quartiles; Q1=4.5-5, Q2=5.1-5.5, Q3=5.6-6, and Q4=>6. Data was analysed using SPSS 26. RESULTS: Of the 218 patients, 141(64.7%) were females and 77(35.3%) were males. The overall mean age was 49.22±11.46 years. There were 102(46.8%) overweight patients, 33(15.1%) obese and 82(37.2%) had normal weight. There were 58(26.6%) patients in Q1, 86(39.4%) in Q2, 46(21.1%) in Q3 and 28(12.8%) in Q4. Those in Q4 showed elevated fasting plasma glucose, glycated haemoglobin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance and urine albumin-to-creatinine ratio (p<0.05), as well as low values for high-density lipoprotein cholesterol and estimated glomerular filtration rate(p<0.05). Fasting serum insulin was negatively linked to glycated haemoglobin (r=-0.12, p=0.07). Triglyceride-glucose index (r=0.76, p<0.001), homeostasis model assessment of insulin resistance (r=0.48, p<0.001), and urine albumin-to-creatinine ratio (r=0.10,p=0.05) positively correlated with glycated haemoglobin. Fasting serum insulin (r=-0.13, p=0.05), negatively correlated with triglyceride-glucose index, while homeostasis model assessment of insulin resistance (r= 0.32, p<0.001) and urine albumin-to-creatinine ratio (r=0.28, p=0.05) had a positive correlation. The estimated glomerular filtration rate was significantly positively linked with fasting serum insulin (r=0.05, p=0.05), and correlated significantly negatively with triglyceride-glucose index (r=-0.35, p=0.01), homeostasis model assessment of insulin resistance (r=-0.01, p=0.86) and urine albumin-to-creatinine ratio (r=-0.02, p=0.8). CONCLUSIONS: The triglyceride-glucose index showed a strong association with homeostasis model assessment of insulin resistance, and surpassed it in terms of predicting diabetic nephropathy in type 2 diabetes mellitus patients.

Implementation research: a protocol for two three-arm pragmatic randomised controlled trials on continuous glucose monitoring devices in people with type 1 diabetes in South Africa and Kenya.

BACKGROUND: Self-monitoring of glucose is an essential component of type 1 diabetes (T1D) management. In recent years, continuous glucose monitoring (CGM) has provided an alternative to daily fingerstick testing for the optimisation of insulin dosing and general glucose management in people with T1D. While studies have been conducted to evaluate the impact of CGM on clinical outcomes in the US, Europe and Australia, there are limited data available for low- and middle-income countries (LMICs) and further empirical evidence is needed to inform policy decision around their use in these countries. METHODS: This trial was designed as a pragmatic, parallel-group, open-label, multicentre, three-arm, randomised (1:1:1) controlled trial of continuous or periodic CGM device use versus standard of care in people with T1D in South Africa and Kenya. The primary objective of this trial will be to assess the impact of continuous or periodic CGM device use on glycaemic control as measured by change from baseline glycosylated haemoglobin (HbA1c). Additional assessments will include clinical outcomes (glucose variation, time in/below/above range), safety (adverse events, hospitalisations), quality of life (EQ-5D, T1D distress score, Glucose Monitoring Satisfaction Survey for T1D), and health economic measures (incremental cost-effectiveness ratios, quality adjusted life years). DISCUSSION: This trial aims to address the substantial evidence gap on the impact of CGM device use on clinical outcomes in LMICs, specifically South Africa and Kenya. The trial results will provide evidence to inform policy and treatment decisions in these countries. TRIAL REGISTRATION: NCT05944731 (Kenya), July 6, 2023; NCT05944718 (South Africa), July 13, 2023.

Effects of Satureja Khuzestanica supplementation on glycemic indices and lipid profile in type 2 diabetes patients: a randomized controlled clinical-trial.

BACKGROUND: Several studies showed the hypoglycemic and hypolipidemic effects of Satureja Khuzestanica (SK) in animal models. This study aimed to determine the effect of SK supplementation on glycemic and lipid outcomes of patients with type 2 diabetes mellitus (T2DM). METHODS: The study was designed as a double-blind, placebo-controlled, randomized clinical trial using block randomization. Seventy-eight T2DM patients were randomly assigned to intervention (n = 39) or placebo (n = 39) groups. They received SK or placebo in 500 mg capsules daily for 12 weeks. Anthropometric, blood pressure, liver enzymes, glycemic, and lipid outcomes were measured before and after the intervention. RESULTS: At baseline, there were no significant differences in age, sex, or glycated hemoglobin (HbA1c) levels between the groups. SK supplementation led to a significant decrease in FBS (-12.6 ± 20.7 mg/dl in the intervention group versus 3.5 ± 31.9 mg/dl; p = 0.007), HbA1c (-0.28 ± 0.45 in the intervention group versus 0.11 ± 0.54% in the placebo group; p = < 0.001), insulin (-1.65 ± 6.18 in the intervention group versus 2.09 ± 5.90 mIU/L in the placebo group; p = 0.03), total cholesterol (-14.6 ± 21.1 mg/dl in the intervention group versus 8.2 ± 30.9 mg/dl in the placebo group; p < 0.001), LDL-cholesterol (-4.6 ± 15.2 mg/dl in the intervention group versus 5.8 ± 14.6 mg/dl in placebo group; p < 0.001) levels, and significant increase in HDL-cholesterol (3.9 ± 4.9 mg/dl in the intervention group versus 0.9 ± 5.2 mg/dl in placebo group; p = 0.005). CONCLUSION: Based on the study results, SK supplementation may improve glycemic indices and lipid profile of patients with T2DM. Our findings may provide novel complementary treatments without adverse effects for diabetes complications. These results need to be further confirmed in clinical trials. REGISTRATION: This trial has been registered in the Iranian Registry of Clinical Trials (IRCT ID: IRCT20190715044214N1, registration date: 21/02/2021).