Glucagon-like peptide-1 (GLP-1) receptor agonists represent efficacious therapies for treating type 2 diabetes. Oral semaglutide is the only orally administered GLP-1 receptor agonist currently available and has been associated with reductions in glycated hemoglobin and body weight versus once-daily injectable liraglutide after 52 weeks in the PIONEER 4 clinical trial. As lower-cost liraglutide formulations have recently been developed, the present analysis evaluated the long-term cost-effectiveness of oral semaglutide 14 mg versus liraglutide 1.8 mg at lower acquisition costs in the UK.

The published and validated PRIME Type 2 Diabetes Model was used to project clinical and cost outcomes over patient lifetimes. Baseline cohort characteristics, as well as treatment-specific changes in physiological parameters and hypoglycemia rates, were sourced from PIONEER 4. Patients were modeled to receive oral semaglutide or liraglutide until HbA1c exceeded 8.0% (64 mmol/mol), after which treatment was intensified to basal insulin. Annual disutilities associated with treatment administration were applied to capture the differential impact of a once-daily oral versus once-daily injectable medication on quality of life. Costs, expressed in 2022 pounds sterling (GBP), were calculated from a National Health Service (NHS) perspective. The acquisition cost of liraglutide was reduced by up to 50% at increments of 5% across a range of scenarios.

Oral semaglutide was associated with improved quality-adjusted life expectancy of 0.18 quality-adjusted life years versus liraglutide 1.8 mg due to a reduced incidence of diabetes-related complications and a reduced treatment-administration burden. Direct, per-person complication costs were estimated to be GBP 187 lower with oral semaglutide. Oral semaglutide remained dominant or cost-effective in the majority of scenarios, even with liraglutide price reductions of 50% applied.

Oral semaglutide 14 mg was projected to be cost-effective versus lower-cost liraglutide 1.8 mg in the UK.

To analyze the difference in type 2 diabetes mellitus (T2DM) disability costs subsidized by the Mexican Social Security Institute for employees with normoglycemia and normotension (n = 547 488) from the 2016 to 2018 National Census of Workers with T2DM registered with the Mexican Social Security Institute.

We tested whether the control of these indicators reduced disability payments at work, the costs of subsidy distribution in different salary groups, and their associated diseases.

Differences (P < .001) emerged in disability leave costs for employees who did not control their blood pressure. Highest-earning employees had the highest costs compared with lower-earning workers. The most frequent subsidized diseases included gastric problems, lower-back disorders, and respiratory infections.

Based on data from all the insured employees with T2DM registered in the National Census, this study enjoyed strong internal validity, indicating that failure to control blood pressure levels correlated with higher costs. The highest costs resulted from noncomplicated diseases. Employees earning higher incomes accounted for the highest costs, suggesting the existence of unequal subsidy conditions.

This study investigates the association between estimated glucose disposal rate (eGDR), a measurement of insulin resistance, and microvascular and macrovascular complications in patients with type 2 diabetes (T2D).

This cross-sectional study enrolled 7471 patients with T2D from 2010 to 2023. The eGDR was calculated using waist circumference, HbA1C levels, and hypertension status. Logistic regression analysis and restricted cubic splines were utilised to examine the relationship between eGDR and vascular complications, including nephropathy, retinopathy, and coronary artery disease (CAD). The robustness of the results and between-group interactions were examined by sensitivity and subgroup analysis. Furthermore, receiver operating characteristic (ROC) curve analysis was employed to assess the discriminatory value of the adjusted model for T2D vascular complications.

Among participants, 56.5% were female, with a mean age of 57.04 ± 11.05 years and a median of 8 years of diabetes duration. In the final adjusted model, each unit increase in the standard deviation of eGDR was significantly associated with a 23.6%, 24.8% and 29.6% decrease in the odds of nephropathy, retinopathy, and CAD, respectively. There was a significant association between higher eGDR quartiles compared to Q1 for all complications (p < 0.05). The Q4 group had the lowest adjusted odds ratios (ORs) compared to the Q1 group for all complications; the OR of Q4 was 0.549 for nephropathy, 0.360 for retinopathy, and 0.396 for CAD (p < 0.001). The restricted cubic spline for nephropathy followed a negative nonlinear association with eGDR, whereas for retinopathy and CAD, it followed a negative linear pattern. The effect of eGDR was consistent among different subgroups. The ROC curve analysis of the adjusted model showed good discriminatory power for all complications.

In patients with type 2 diabetes, a higher eGDR was significantly associated with a lower risk of microvascular and macrovascular complications, regardless of well-known confounders.

Background and Objective: Diabetic peripheral neuropathy (DPN) is a prevalent complication of type 2 diabetes mellitus (T2DM), with nerve conduction studies (NCSs) serving as the diagnostic gold standard. Early diagnosis is critical for effective management, yet many cases are detected late due to the gradual onset of symptoms. This study explores the relationship between hematological tests and NCS outcomes in T2DM patients to improve the early detection of DPN. Material and Methods: This retrospective study involved T2DM patients exhibiting neuropathic symptoms, and patients were divided based on NCS findings into groups with normal and abnormal results to assess the diagnostic value of various hematological markers, clinical, and demographic data for DPN. Results: Among 400 participants, 57% (n = 228) had abnormal NCS results indicative of DPN. Significant differences were observed in the abnormal-NCS group, including older age, longer diabetes duration, higher levels of fasting plasma glucose, HbA1c, and apolipoprotein B, along with lower eGFR, HDL-C, and Apo A-I levels. Notably, negative correlations were found between HDL-C, Apo A-I, vitamin B12, and specific NCS measurements, while positive correlations existed with sural sensory nerve amplitudes. Multivariate analysis highlighted the importance of age, diabetes duration, hyperglycemia, and specific hematologic markers in predicting DPN. Conclusions: The findings confirm that NCSs, combined with hematologic testing, can effectively identify DPN in T2DM patients. Consistent with prior research, prolonged hyperglycemia and nephropathy progression are strongly linked to DPN development. Additionally, lower levels of HDL-C, Apo A-I, and vitamin B12 are associated with the condition, suggesting their potential utility in early diagnostic protocols.

Type 2 diabetes (T2DM) is known to have detrimental effects on renal health. Our study aimed to investigate the relationship between remnant cholesterol (remnant-C) and adverse renal outcomes in patients with T2DM.

We utilized data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which included 10,196 participants with T2DM to investigate the relationship between remnant-C and adverse renal outcomes by performing Kaplan-Meier survival analysis, Cox proportional regression and Restricted cubic spline (RCS) analysis. Finally, several sensitivity analyses were conducted to assess the robustness of our findings.

Over a 7-year follow-up period, 2039 patients (23.2%) developed albuminuria, 5824 patients (57.1%) experienced worsening renal function, and 280 patients (2.7%) progressed to renal failure. After adjusting for multiple confounding factors, we found that remnant-C was significantly associated with the development of albuminuria (P = 0.007) and worsening renal function (P = 0.002). However, there was no discernible connection between remnant-C and renal faiure (P = 0.621). In sensitivity analyses, the association between remnant-C and the risk of adverse renal outcomes remained robust.

Our findings highlight the association between remnant-C and the risk of adverse renal outcomes in patients with T2DM. This easily calculable index can provide valuable information to physicians for predicting the risk of adverse renal outcomes in patients with T2DM.

To evaluate systemic vascular fitness measured by finger photoplethysmography in diabetic retinopathy (DR).

This was a cross-sectional observational study on patients with Type II diabetes mellitus from October 2020 to May 2021. Data collected include systolic/diastolic blood pressure, visual acuity, glycated hemoglobin, and central macular thickness. Diabetic retinopathy severity was categorized using the Early Treatment Diabetic Retinopathy Study classification. Photoplethysmography signals were acquired using pulse-oximeter modules (OEM-60; Dolphin Medical, Inc) measured for 90 seconds at 275 Hz sampling rate and 16-bit resolution, which records photoplethysmography fitness index, vascular risk prediction index, and vascular age.

One hundred and forty-one patients were equally distributed into six DR categories. Mean age was 58.8 ± 9.9 years, with female-to-male ratio of 1.27. There were significant differences in mean systolic (125.5 ± 10.0 mmHg, P = 0.007) and diastolic blood pressure (80.0 ± 8.8 mmHg), mean glycated hemoglobin (7.6 ± 1.9%, P = 0.005), median log unit of minimal angle of resolution (0.3, interquartile range: 0.2-0.5, P < 0.001), and central macular thickness ( P = 0.003) across DR severity. Significant differences were also seen in photoplethysmography fitness index ( P = 0.001), vascular risk prediction index ( P < 0.001), and vascular age ( P = 0.001), with poorer values in severe compared with mild/moderate DR. After adjusting for age, blood pressure, and glycated hemoglobin, photoplethysmography fitness reduces by 3.3% (regression coefficient, b = -3.27, P < 0.001), vascular age increases by 2.5 years ( b = 2.54, P = 0.002), and vascular risk prediction index increases by 3.1 ( b = 3.08, P < 0.001) with every DR worsening.

More severe DR stages were associated with poorer photoplethysmography vascular markers.

An aging population combined with a rapidly increasing prevalence of diabetes foreshadows a global epidemic of cardiovascular and kidney disease that threatens to halt improvements in life and health-span and will have particularly severe consequences in older adults. The management of diabetes has been transformed with the recent development of newer anti-hyperglycemic agents that have demonstrated superior efficacy. However, the utility of these drugs extends beyond glycemic control to benefits for managing obesity, cardiovascular disease (CVD), chronic kidney disease, and heart failure. Numerous cardiovascular and kidney outcomes trials of these drugs have played an instrumental role in shaping current guidelines for the management of diabetes and CVD. Older adults with diabetes are diverse in terms of their comorbidities, diabetic complications, and cognitive and functional status. Therefore, there is an unmet need for personalized management of diabetes and CVD in this population. In this review, we provide an overview of the epidemiological burden and management of diabetes and CVD in older adults. We then focus on randomized cardiovascular and kidney outcome trials with anti-hyperglycemic agents to propose an evidence-based approach to the management of diabetes in older adults with high risk of cardiovascular and kidney disease.

The hybrid closed-loop (HCL) system, Medtronic MiniMed™ 770G, has been available for use by Japanese individuals with type 1 diabetes mellitus since 2021. The aim of this study was to evaluate the effect of its use on glycemic variability and quality of life (QOL) in this population. This multicenter, open-label, prospective observational study included 14 Japanese individuals with type 1 diabetes mellitus treated with MiniMed™ 640G. Participants who switched to the 770G system were evaluated for time in range (TIR) and other glycemic outcomes at baseline and at 3 and 12 months post-transition. QOL was assessed using the Diabetes Therapy-Related QOL (DTR-QOL) scale. The mean baseline glycated hemoglobin was 7.52 ± 1.05%, and body mass index (BMI) was 21.78 ± 3.07 kg/m2. By study completion, individuals used the HCL system approximately 80% of the time in a day. TIR showed improvement, with an increased achievement ratio of TIR > 70% at 12 months. Hypoglycemia occurrence was minimal at 12 months. In addition, all-time sensor glucose measurements decreased after 12 months, and there were no significant changes in BMI or daily insulin dose. DTR-QOL scores did not significantly differ, possibly owing to increased total alarms and sensor calibration times. Transitioning to the Medtronic MiniMed™ 770G system led to an improved achievement ratio of TIR > 70% and reduced hyperglycemia at 12 months. However, no significant change in QOL was observed, probably because of the increased number of total alarms.

The online version contains supplementary material available at 10.1007/s13340-024-00778-7.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Newer incretin-based therapies for type 2 diabetes (T2D) have the potential to substantially reduce glycated hemoglobin (HbA1c) and weight with a low associated risk of hypoglycemia. This study aimed to assess the percentage of participants randomized to tirzepatide or comparator who achieved the composite endpoint of HbA1c ≤ 6.5% and weight reduction ≥ 10% without hypoglycemia across prespecified baseline characteristics: T2D duration (≤ 5, > 5-10, or > 10 years), sex, HbA1c (≤ 8.5% or > 8.5%), age (< 65 or ≥ 65 years), and body mass index (< 30, 30 to < 35, or ≥ 35 kg/m2).

This post hoc analysis of SURPASS-1 through -5 evaluated adult study participants with T2D treated with tirzepatide 5, 10, or 15 mg versus placebo or active comparator. Missing HbA1c and weight values were imputed from mixed models for repeated measures. Logistic regression was used to compare tirzepatide versus comparators for the percentage of participants reaching the composite endpoint.

Across subgroups, the composite endpoint was achieved by a median of approximately 30%, 45%, and 54% of participants who received tirzepatide 5, 10, and 15 mg, respectively; this was consistent across baseline subgroups, except that a greater percentage of women than men achieved the composite endpoint. The most common treatment-emergent adverse events were gastrointestinal in nature.

In this post hoc analysis, tirzepatide achieved the composite outcome of glycemic control and weight loss with no hypoglycemia, irrespective of baseline characteristics. This may help clinicians as they select suitable treatment in diverse populations.

ClinicalTrials.gov: NCT03954834, NCT03987919, NCT03882970. NCT03730662, and NCT04039503.

The term "Diabetic neuropathy" refers to a collection of clinical and subclinical symptoms caused by problems with the peripheral nervous system. Diabetes, which affects approximately 381 million people worldwide, is the source of dysfunction due to the emergence of microvascular complications. It is anticipated that in the next ten years, Diabetic neuropathy will manifest in about 50% of patients who are currently diagnosed with diabetes. Clinical diagnosis can be established by getting a thorough patient history and exploring the symptoms to rule out alternative causes. Although distal symmetrical polyneuropathy, or just, is the most common and well-researched variant of the disorder, this review will concentrate on it. The multifactorial pathogenesis is linked to various inflammatory, vascular, metabolic, and neurodegenerative illnesses. The three fundamental molecular alterations that lead to the development of diabetic neuropathic pain are oxidative stress, endothelial dysfunction, and chronic inflammation. These three elements are crucial in the development of polyneuropathy because their combination might result in direct axonal damage and nerve ischemia. The purpose of this article was to provide a narrative review of diabetic neuropathy. We provide an overview of the most recent data on biomarkers, the pathogenesis of the illness, the most recent epidemiology of diabetic neuropathy, and the existing screening and diagnosis outcome measures used in both clinical and research contexts.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Cardiovascular disease (CVD) and diabetes mellitus are prominent public health concerns in Saudi Arabia owing to their increasingly high prevalence and burden. Based on this, the Saudi Heart Association (SHA) set out to develop an official position statement on CVD and diabetes mellitus, with a focus on the prevention and management of these conditions and relevant special populations in the context of Saudi Arabia.

A multidisciplinary panel of experts met under the auspices of the SHA in a series of meetings to review and discuss available evidence on the prevention and management of comorbid CVD and diabetes mellitus. Specialized subcommittees reviewed the data and offered context-specific recommendations (taking into account Saudi population characteristics, local healthcare system, available resources and medical expertise), which were later approved by the full expert panel.

The prevalence of diabetes mellitus and CVD is alarming in the Saudi Arabian population. Diabetes mellitus and CVD are interconnected on several levels, including cellular and molecular events as well as epigenetic and genetic mechanisms. Screening for CVD is a priority for patients with diabetes and concomitant risk factors. The expert panel also recommends aggressive management of high blood pressure and dyslipidemia in addition to lifestyle changes and achieving glycemic targets for the prevention of CVD in patients with diabetes. Some glucose-lowering drug classes, namely SGLT2-inhibitors and GLP-1 receptor agonists, offer significant benefits on the level of cardiovascular risk reduction and are thus a powerful addition to the clinical management armamentarium in CVD and diabetes. Special consideration is also advised for patient populations with distinct clinical presentation and needs, such as coronary artery disease, heart failure, and chronic kidney disease, among others.

To conduct a systematic review to assess drug exposure handling in diabetic retinopathy (DR) risk prediction models, a network-meta-analysis to identify drugs associated with DR and a meta-analysis to determine which drugs contributed to enhanced model performance.

Systematic review and meta-analysis.

We included studies presenting DR models incorporating drug exposure as a predictor. We searched EMBASE, MEDLINE, and SCOPUS from inception to December 2023. We evaluated the quality of studies using the Prediction model Risk of Bias Assessment Tool and certainty using GRADE. We conducted network meta-analysis and meta-analysis to estimate the odds ratio (OR) and pooled C-statistic, respectively, and 95% confidence intervals (CI) (PROSPERO: CRD42022349764).

Of 5,653 records identified, we included 28 studies of 678,837 type 1 or 2 diabetes participants, of which 38,579 (5.7%) had DR. A total of 19, 3, and 7 studies were at high, unclear, and low risk of bias, respectively. Drugs included in models as predictors were: insulin (n = 24), antihypertensives (n = 5), oral antidiabetics (n = 12), lipid-lowering drugs (n = 7), antiplatelets (n = 2). Drug exposure was modelled primarily as a categorical variable (n = 23 studies). Two studies handled drug exposure as time-varying covariates, and one as a time-dependent covariate. Insulin was associated with an increased risk of DR (OR = 2.50; 95% CI: 1.61-3.86). Models that included insulin (n = 9) had a higher pooled C-statistic (C-statistic = 0.84, CI: 0.80-0.88), compared to models (n = 9) that incorporated a combination of drugs alongside insulin (C-statistic = 0.79, CI: 0.74-0.84), as well as models (n = 3) not including insulin (C-statistic = 0.70, CI: 0.64-0.75). Limitations include the high risk of bias and significant heterogeneity in reviewed studies.

This is the first review assessing drug exposure handling in DR prediction models. Drug exposure was primarily modelled as a categorical variable, with insulin associated with improved model performance. However, due to suboptimal drug handling, associations between other drugs and model performance may have been overlooked. This review proposes the following for future DR prediction models: (1) evaluation of drug exposure as a variable, (2) use of time-varying methodologies, and (3) consideration of drug regimen details. Improving drug exposure handling could potentially unveil novel variables capable of significantly enhancing the predictive capability of prediction models.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, yet varying estimates of its prevalence exist. The present study aimed to estimate a questionnaire-centered prevalence of painful and painless DPN in the Northern Danish Region, examine its geographical distribution within the region, and investigate associations between DPN and potential risk factors.

A questionnaire-based survey was sent to all persons living with diabetes in the Northern Danish Region using electronic mail. Persons with diabetes were identified using The National Health Insurance Service Registry. The survey included information on demographics, socioeconomics, municipality, diabetes type, duration, and treatment, as well as the validated questionnaires Michigan Neuropathy Screening Instrument-questionnaire (MNSIq) and the Douleur Neuropathique en 4 Questions (DN4)-interview. Possible DPN was defined as an MNSIq-score ≥ 4, while possible painful DPN was defined as pain in both feet and a DN4-interview score ≥ 3.

A total of 23,206 eligible people were identified as having diabetes and approximately 33 % answered all questionnaires. The prevalence of possible DPN was 23.3 % (95 % CI: 22.4-24.3 %), while the prevalence of possible painful DPN was 18.0 % (17.1-18.8 %). The prevalence of possible DPN ranged from 22.1 % to 35.0 % between municipalities, while the prevalence of possible painful DPN ranged from 15.6 % to 20.0 %. High body-mass index, long diabetes duration, insulin use, glucagon-like-peptide-1-analogue use, and low income were associated with increased risk of DPN.

The high prevalence of possible painless and painful DPN emphasizes the need for better prevention and careful screening even in high-income countries.

This study evaluated the effects of black tea drinks with inulin and dextrin (BTID) on postprandial plasma glucose (PG) in patients with type 2 diabetes mellitus (T2DM).

An acute, randomized, double-blind, placebo-controlled, crossover clinical trial was carried out on T2DM patients. The subjects were randomly assigned to groups consuming placebo black tea powder or BTID (identically packaged) followed by a mixed meal tolerance test (MMTT). Afterwards, individuals who initially consumed BTID were given the placebo and those who initially consumed the placebo were given BTID.

A total of 35 patients were included in the study, and 32 completed the study. Compared to placebo, BTID significantly reduced the change in glycaemia at 30 min, 1, 2, and 3 h during the MMTT. In the analysis of PG fluctuations at 2 h during the MMTT, the proportion of patients with minor PG fluctuations (< 2.8 mmol/L) in the BTID group was 53.1%, significantly higher than the 28.1% in the placebo group. Binary logistic regression analysis revealed that the risk of significant PG fluctuations decreased by 65.5% after consuming BTID, with a corresponding odds ratio of 0.345 (P = 0.044, 95% CI 0.122-0.974). In addition, the areas under the curve for PG and insulin secretion after BTID administration were significantly smaller than that for placebo.

Compared to placebo, BTID significantly reduced the change in PG levels during the MMTT and decreased the risk of large PG fluctuations by 65.5%. These effects were associated to a significant reduction in postprandial insulin secretion and may help to improved insulin sensitivity and a lower β-cell burden.

Diabetic neuropathy (DN) is an important complication of diabetes mellitus. Autophagy is considered to be potentially involved in the regulation of DN. Metformin is broadly utilized in the first-line treatment of diabetes. The present work aimed to assess whether and how metformin exerts protective effects in DN.

A DN rat model induced by streptozotocin (STZ) was established. Metformin was administered to examine its effect on sciatic nerve pathology, and the possible mechanisms involved in this process were explored.

Morphological damage was observed in sciatic nerve samples from diabetic animals, accompanied by decreased p-AMPK expression and increased LC-3 levels. Notably, metformin ameliorated the morphological changes in the sciatic nerve by downregulating autophagy via p-AMPK upregulation.

These results indicate that metformin attenuates peripheral neuropathy in diabetic rats by regulating autophagy.

Therapeutic inertia in type 2 diabetes, defined as a failure to intensify treatment despite poor glycemic control, can arise due to a variety of factors, despite evidence linking improved glycemic control with reductions in diabetes-related complications. The present study aimed to evaluate the health and economic burden of therapeutic inertia in people with type 2 diabetes in Saudi Arabia.

The IQVIA Core Diabetes Model (v.9.0) was used to evaluate outcomes. Baseline cohort characteristics were sourced from Saudi-specific data, with baseline glycated hemoglobin (HbA1c) tested at 8.0%, 9.0%, and 10.0%. Modeled subjects were brought to an HbA1c target of 7.0% immediately or after delays of 1-5 years across time horizons of 3-50 years. Outcomes were discounted annually at 3.0%. Costs were accounted from a societal perspective and expressed in 2023 Saudi Arabian Riyals (SAR).

Immediate glycemic control was associated with improved or equal life expectancy and quality-adjusted life expectancy and cost savings in all scenarios compared with delays in achieving target HbA1c. Combined cost savings ranged from SAR 411 (EUR 102) per person with a baseline HbA1c of 8.0% versus a 1-year delay over a 3-year time horizon, to SAR 21,422 (EUR 5291) per person with a baseline HbA1c of 10.0% versus a 5-year delay over a 50-year time horizon. Discounted life expectancy and quality-adjusted life expectancy were projected to improve by up to 0.4 years and 0.5 quality-adjusted life years (QALYs), respectively, with immediate glycemic control.

Therapeutic inertia was associated with a substantial health and economic burden in Saudi Arabia. Interventions and initiatives that can help to reduce therapeutic inertia are likely to improve health outcomes and reduce healthcare expenditure.

Diabetic peripheral neuropathy (DPN) affects ∼50% of the 500 million people with type 2 diabetes worldwide and is considered disabling and irreversible. The current study was undertaken to assess the effect of metformin on peripheral neuropathy outcomes in type 2 diabetes. Participants with type 2 diabetes (n = 69) receiving metformin were recruited and underwent clinical assessment, peripheral nerve ultrasonography, nerve conduction studies, and axonal excitability studies. Also concurrently screened were 318 participants who were not on metformin, and 69 were selected as disease control subjects and matched to the metformin participants for age, sex, diabetes duration, BMI, HbA1c, and use of other diabetes therapies. Medical record data over the previous 20 years were analyzed for previous metformin use. Mean tibial nerve cross-sectional area was lower in the metformin group (metformin 14.1 ± 0.7 mm2, nonmetformin 16.2 ± 0.9 mm2, P = 0.038), accompanied by reduction in neuropathy symptom severity (P = 0.021). Axonal excitability studies demonstrated superior axonal function in the metformin group, and mathematical modeling demonstrated that these improvements were mediated by changes in nodal Na+and K+conductances. Metformin treatment is associated with superior nerve structure and clinical and neurophysiological measures. Treatment with metformin may be neuroprotective in DPN.

Type 2 diabetes (T2D) is a disease characterized by heterogeneously progressive loss of islet β cell insulin secretion usually occurring after the presence of insulin resistance (IR) and it is one component of metabolic syndrome (MS), and we named it metabolic dysfunction syndrome (MDS). The pathogenesis of T2D is not fully understood, with IR and β cell dysfunction playing central roles in its pathophysiology. Dyslipidemia, hyperglycemia, along with other metabolic disorders, results in IR and/or islet β cell dysfunction via some shared pathways, such as inflammation, endoplasmic reticulum stress (ERS), oxidative stress, and ectopic lipid deposition. There is currently no cure for T2D, but it can be prevented or in remission by lifestyle intervention and/or some medication. If prevention fails, holistic and personalized management should be taken as soon as possible through timely detection and diagnosis, considering target organ protection, comorbidities, treatment goals, and other factors in reality. T2D is often accompanied by other components of MDS, such as preobesity/obesity, metabolic dysfunction associated steatotic liver disease, dyslipidemia, which usually occurs before it, and they are considered as the upstream diseases of T2D. It is more appropriate to call "diabetic complications" as "MDS-related target organ damage (TOD)", since their development involves not only hyperglycemia but also other metabolic disorders of MDS, promoting an up-to-date management philosophy. In this review, we aim to summarize the underlying mechanism, screening, diagnosis, prevention, and treatment of T2D, especially regarding the personalized selection of hypoglycemic agents and holistic management based on the concept of "MDS-related TOD".

Chronic kidney disease (CKD) is a very important issue globally because of the risk of its progressing to end-stage renal disease. We aimed to identify factors contributing to long-term estimated glomerular filtration rate (eGFR) decline to determine an early diagnosis and prevent CKD progression.

From January 2003 to December 2006, 5,507 individuals underwent health checkups at our hospital's Preventive Medicine Research Center. We ultimately enrolled 2,175 individuals. The eGFR was ≥60 mL/min/1.73 m2 at the start of observation period, which was 20 years. The event onset time was the day that the eGFR became <30 mL/min during the 20-year period. Baseline risk factors - in particular, the effect of plasma glucose levels on the eGFR - were extracted and evaluated by using Fine and Gray analysis.

During the 20-year observation, the hazard ratio (HR) of CKD progression was examined. A fasting plasma glucose (FPG) level ≥105 mg/dL was significantly associated with the risk of CKD progressing to an eGFR <30 mL/min. This trend was similar in the slope of eGFR. An FPG ≥105 mg/dL or an glycated hemoglobin level ≥6.5% was useful for intervening in CKD progression. Multivariate analysis showed that independent risk factors were an FPG level ≥105 mg/dL (HR 1.9; P < 0.001), age ≥60 years (HR 3.86; P < 0.001), obesity (HR 1.61; P < 0.01) and urinary protein (HR 1.55; P < 0.01).

For early intervention against a reduction in the eGFR, detecting mild increases in FPG ≥105 mg/dL in patients with CKD with or without diabetes is useful.

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM), affecting over one-third of type 1 and nearly half of type 2 diabetes patients. As the leading cause of end-stage renal disease (ESRD) globally, DKD develops through a complex interplay of chronic hyperglycemia, oxidative stress, and inflammation. Early detection is crucial, with diagnosis based on persistent albuminuria and reduced estimated glomerular filtration rate (eGFR). Treatment strategies emphasize comprehensive management, including glycemic control, blood pressure regulation, and the use of nephroprotective agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists. Ongoing research explores novel therapies targeting molecular pathways and non-coding RNAs. Preventive measures focus on rigorous control of hyperglycemia and hypertension, aiming to mitigate disease progression. Despite therapeutic advances, DKD remains a leading cause of ESRD, highlighting the need for continued research to identify new biomarkers and innovative treatments.

The prevalence of cardiovascular diseases (CVDs) is well known. According to the World Health Organization (WHO), almost 18 million people die from CVDs worldwide every year, accounting for 31% of all causes of death [1]. CVDs often develop concomitantly with diabetes mellitus (DM), with approximately 20% of cardiovascular deaths attributed to elevated blood glucose levels [2]. Notably, CVDs are the leading cause of death among patients with type 2 diabetes (T2DM). Based on data from the Federal Register of Diabetes 2022 in Russia, chronic heart failure was the direct cause of death in 24.2% of T2DM cases, followed by acute heart failure (13.1%), cerebrovascular events (10.0%), and myocardial infarction (3.7%) [3].The pathophysiological interplay between atherosclerotic cardiovascular disease and DM has led to a situation where cardiologists are increasingly involved in the treatment of patients with DM, while endocrinologists are encountering a growing number of patients with CVDs. This association has become so apparent that in a recent article published in the European Journal of Cardiology, Yu. Braunwald speculated about the emergence of a new subspecialty - diabetocardiology [4]. Unfortunately, experts predict that the global number of diabetic patients will reach 783 million [5].Recent data on the CV benefits of certain hypoglycemic drugs (primarily, certain SGLT2 inhibitors, several GLP-1 receptor agonists, and a novel non-steroidal mineralocorticoid receptor antagonist finerenone) prove the need for a unified interdisciplinary approach to managing CVDs and DM.Given the importance of integrated and coordinated efforts in managing patients with CVD and DM, the Task Force of the -European Society of Cardiology (ESC) updated, formulated, and published clinical guidelines on the treatment of CVD in diabetic patients in 2023 [6]. This article provides a concise overview of the key provisions outlined in the guidelines.

Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder characterized by insulin resistance and progressive beta cell dysfunction, presenting substantial global health and economic challenges. This review explores recent advancements in diabetes management, emphasizing novel pharmacological therapies and their physiological mechanisms. We highlight the transformative impact of Sodium-Glucose Cotransporter 2 inhibitor (SGLT2i) and Glucagon-Like Peptide 1 Receptor Agonist (GLP-1RA), which target specific physiological pathways to enhance glucose regulation and metabolic health. A key focus of this review is tirzepatide, a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors. Tirzepatide illustrates how integrating innovative mechanisms with established physiological pathways can significantly improve glycemic control and support weight management. Additionally, we explore emerging treatments such as glimins and glucokinase activators (GKAs), which offer novel strategies for enhancing insulin secretion and reducing glucose production. We also address future perspectives in diabetes management, including the potential of retatrutide as a triple receptor agonist and evolving guidelines advocating for a comprehensive, multifactorial approach to care. This approach integrates pharmacological advancements with essential lifestyle modifications-such as dietary changes, physical activity, and smoking cessation-to optimize patient outcomes. By focusing on the physiological mechanisms of these new therapies, this review underscores their role in enhancing T2DM management and highlights the importance of personalized care plans to address the complexities of the disease. This holistic perspective aims to improve patient quality of life and long-term health outcomes.

Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences  is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

We examined the trajectory of estimated glomerular filtrate rate (eGFR), associated risk factors, and its relationship with end-stage kidney disease (ESKD) among a multiethnic patient population with type 2 diabetes in Singapore.

A follow-up study included 62 080 individuals with type 2 diabetes aged ≥18 years in a multi-institutional SingHealth Diabetes Registry between 2013 and 2019. eGFR trajectories were analyzed using latent class linear mixed models. Factors associated with eGFR trajectories were evaluated using multinomial logistic regression. The association of eGFR trajectories with ESKD was assessed via competing risk models.

Trajectory of kidney function, determined by eGFR, was nonlinear. The trajectory pattern was classified as stable initially then gradual decline (75%), progressive decline (21.9%), and rapid decline (3.1%). Younger age, female sex, Malay ethnicity, lower-income housing type, current smoking, higher glycated hemoglobin, lower low-density lipoprotein, higher triglyceride, uncontrolled blood pressure, albuminuria, cardiovascular disease, hypertension, and higher eGFR levels each were associated with progressive or rapid decline. Compared with the trajectory of stable initially then gradual eGFR decline, progressive decline increased the hazard of ESKD by 6.14-fold (95% confidence interval [CI]: 4.96-7.61)) and rapid decline by 82.55 folds (95% CI: 55.90-121.89).

Three nonlinear trajectory classes of kidney function were identified among multiethnic individuals with type 2 diabetes in Singapore. About one in four individuals had a progressive or rapid decline in eGFR. Our results suggest that eGFR trajectories are correlated with multiple social and modifiable risk factors and inform the risk of ESKD.

There is a need for knowledge regarding the natural course of diabetic polyneuropathy (DPN), a complication in type 2 diabetes (T2D). The aim of this study was to examine the development of DPN over time.

Patients with newly diagnosed T2D, recruited from a national cohort, and controls without diabetes of similar age and sex, underwent sensory phenotyping in 2016-2018. The Toronto consensus criteria were used to classify patients into possible, probable, and confirmed DPN. For this 5-year, observational, follow-up, cohort study, all participants were invited to a reexamination combining bedside sensory examination, quantitative sensory testing (QST), nerve conduction studies (NCSs), and skin biopsies measuring intraepidermal nerve fiber density (IENFD) in order to compare phenotypic and diagnostic changes over time.

Of the baseline 389 patients and 97 controls, 184 patients (median [interquartile range] diabetes duration 5.9 [4.1-7.4] years, mean hemoglobin A1c [HbA1c] 51 ± 11 mmol/mol at baseline) and 43 controls completed follow-up (46.9%). Confirmed DPN was present in 35.8% and 50.3%, probable DPN in 27.2% and 14.6%, possible DPN in 17.2% and 16.6%, and no DPN in 15.2% and 17.9% at baseline and follow-up, respectively. The estimated prevalence (95% CI) of confirmed DPN was 33.5% (24.9-42.1) compared with 22.7% (17.5-28.0) at baseline. During the follow-up period, 43.9% of patients with probable DPN developed confirmed DPN. Progression of neuropathy occurred in 16.5% and 24.7% and regression in 5.9% and 18.6% of patients based on NCS and IENFD, respectively. Progression based on NCS and/or IENFD was associated with higher baseline waist circumference and triglycerides, and regression with lower baseline HbA1c. Patients with at least probable DPN at baseline but neither patients without DPN nor controls developed increased spread of hyposensitivity, more hyposensitivity on QST and lower NCS z-scores at follow-up, and worsening of nerve parameters at follow-up correlated with higher baseline triglycerides.

In patients with well-regulated T2D, the proportion of patients with confirmed DPN increased over 5 years driven by progression from probable DPN. A large proportion of patients progressed, and a smaller proportion regressed on nerve parameters. Higher triglycerides correlated with this progression and may constitute a risk factor.

Diabetic peripheral neuropathy (DPN) is highly prevalent among Jordanian patients, mostly are asymptomatic. Early recognition and appropriate management of neuropathy is important to improve symptoms, reduce sequelae, and improve quality of life. This study aims at exploring the role of pharmacists in the early recognition of DPN and providing quick screening for the presence of it among diabetic patients.

A cross-sectional study was conducted at multi-pharmacy settings, in Irbid, Jordan. Twenty trained pharmacists who had bachelor's degrees in pharmacy participated in data collection. A total of 400 patients with confirmed diagnosis of type 2 diabetes mellitus (DM) according to the World Health Organization diagnostic criteria were recruited. DPN was assessed using the translated Arabic version of Michigan Neuropathy Screening Instrument (MNSI) history version.

The mean MNSI questionnaire score for all participants was 4.40 ± 3.00. Mean age of the patients was 62.6 ± 10.7 years old and duration of diabetes was 8.25 ± 6.9. DN was present in 23.7% of the population. Diabetic patients with neuropathy were older than patients without neuropathy (p < 0.05) and had had diabetes longer (p < 0.05). Poor glycemic control, hypertension and gender, were significantly risk factors for DN (p < 0.05).

In addition to delivering medications, this study suggests that pharmacists can have a role in screening and counseling about diabetic peripheral neuropathy using a simple objective, and non-invasive tool and also can determine level of damage and risk.

Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes mellitus that can lead to end-stage renal disease. Colquhounia root tablet (CRT) has shown therapeutic potential in treating DKD, but its efficacy and underlying mechanisms remain to be elucidated.

A randomized controlled clinical trial was conducted on 61 DKD patients. The treatment group received CRT in addition to standard therapy, while the control group received standard therapy alone. Treatment efficacy and adverse events were evaluated after 3 months. Additionally, in vitro experiments using human renal tubular epithelial cells (HK-2) were performed to investigate the effect of CRT on high glucose (HG)-induced epithelial-mesenchymal transition (EMT) and the involvement of the PTEN/PI3K/AKT signaling pathway.

CRT treatment significantly improved proteinuria and increased the effective treatment rate in DKD patients compared to the control group, with no significant difference in adverse events. Moreover, CRT reversed HG-induced EMT in HK-2 cells, as evidenced by the downregulation of α-SMA and upregulation of E-cadherin at both mRNA and protein levels. Mechanistically, CRT increased PTEN expression and inhibited the PI3K/AKT pathway, similar to the effects of the PI3K inhibitor LY29400. The combination of CRT and LY29400 further enhanced PTEN mRNA expression under HG conditions.

CRT effectively improves proteinuria in DKD patients and ameliorates HG-induced EMT in HK-2 cells. The underlying mechanism may involve the upregulation of PTEN and subsequent inhibition of the PI3K/AKT signaling pathway. These findings provide new insights into the therapeutic potential of CRT for DKD treatment.

The role of glycemic control and its variability on the rate of kidney function decline after the onset of diabetic kidney disease (DKD) remains unclear.

The association between baseline glycated hemoglobin (HbA1c) and rates of estimated glomerular filtration rate (eGFR) loss during follow-up was examined by mixed-effects linear regression in 530 individuals with type 1 diabetes and early-to-moderate DKD from the Preventing Early Renal Loss (PERL) trial and 2378 individuals with type 2 diabetes and established DKD from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. The benefit of intensive vs standard glycemic control in slowing eGFR decline was examined in ACCORD. The associations between continuous glucose monitoring-derived short-term glycemic variability indices and rate of eGFR decline were also evaluated in PERL.

A higher baseline HbA1c was associated with a more negative eGFR slope in both PERL and ACCORD (-0.87 and -0.27 mL/min/1.73 m2/year per Hba1c unit increment, P < .0001 and P = .0002, respectively). In both studies, the strength of this association progressively increased with increasing levels of albuminuria (P for interaction <.05). Consistent with this, the benefit of intensive glycemic control on eGFR decline was greater in ACCORD participants with severe rather than moderate albuminuria (+1.13 vs + 0.26 mL/min/1.73 m2/year, P = .01). No independent associations were found in PERL between short-term glycemic variability indices and rate of eGFR decline.

In both type 1 and type 2 diabetes, poor glycemic control is associated with a more rapid rate of glomerular filtration rate decline after DKD onset, especially in persons with severe albuminuria.

Insulin resistance (IR) is becoming a worldwide medical and public health challenge as an increasing prevalence of obesity and metabolic disorders. Accumulated evidence has demonstrated a strong relationship between IR and a higher incidence of several dramatically vision-threatening retinal diseases, including diabetic retinopathy, age-related macular degeneration, and glaucoma. In this review, we provide a schematic overview of the associations between IR and certain ocular diseases and further explore the possible mechanisms. Although the exact causes explaining these associations have not been fully elucidated, underlying mechanisms of oxidative stress, chronic low-grade inflammation, endothelial dysfunction and vasoconstriction, and neurodegenerative impairments may be involved. Given that IR is a modifiable risk factor, it may be important to identify patients at a high IR level with prompt treatment, which may decrease the risk of developing certain ocular diseases. Additionally, improving IR through the activation of insulin signaling pathways could become a potential therapeutic target.

Treatment for diabetes includes anti-diabetic medication in addition to lifestyle improvements through diet and exercise. In Japan, protocol-based pharmacotherapy management allows drug treatment to be provided through cooperation between physicians and pharmacists, based on a protocol that is prepared and agreed upon in advance. However, there are no studies to clarify the relationship between patient characteristics and therapeutic effects after pharmacist intervention in protocol-based pharmacotherapy management for patients with diabetes. Therefore, this study aimed to use protocol-based reports from pharmacies to understand the status of outpatient diabetes medication compliance. We classified patients with diabetes on the basis of patient characteristics that can be collected in pharmacies and investigated the characteristics that impacted diabetes treatment. Patients were prescribed oral anti-diabetic drugs at outpatient clinics of Hitachinaka General Hospital, Hitachi, Ltd., from April 2016 to March 2021. Survey items included patient characteristics (sex, age, number of drugs used, observed number of years of anti-diabetic drug prescription, number of anti-diabetic drug prescription days, and presence or absence of leftover anti-diabetic drugs) and HbA1c levels. Graphical analyses indicated the relationship between each categorised patient characteristic using multiple correspondence analyses. Subsequently, the patients were clustered using K-means cluster analysis based on the coordinates obtained for each patient. Patient characteristics and HbA1c values were compared between the groups for each cluster. A total of 1,910 patients were included and classified into three clusters, with clusters 1, 2, and 3 containing 625, 703, and 582 patients, respectively. Patient characteristics strongly associated with Cluster 1 were ages between 65 and 74 years, use of three or more anti-diabetic drugs, use of 3 years or more of anti-diabetic drugs, and leftover anti-diabetic drugs. Furthermore, Cluster 1 had the highest number of patients with worsening HbA1c levels compared with other clusters. Using the leftover drug adjustment protocol, we clarified the patient characteristics that affected the treatment course. We anticipate that through targeted interventions in patients exhibiting these characteristics, we can identify those who are irresponsibly continuing with drug treatment, are not responding well to therapy, or both. This could substantially improve the efficacy of their anti-diabetic care.

Unlike systolic blood pressure (SBP), the prognostic value of diastolic blood pressure (DBP) in kidney function has not been established. We hypothesized that pulse pressure (PP), which is associated with arteriosclerosis, would affect the prognostic value of DBP.

This longitudinal study used data from the Japan Specific Health Checkups Study was conducted between 2008 and 2014. The participants were stratified into three PP subgroups (low PP ≤39, normal PP 40-59 and high PP ≥60 mmHg). The exposures of interest were SBP and DBP, and the association between SBP/DBP and kidney outcomes (30% decline in the estimated glomerular filtration rate from baseline) was examined in each PP subgroup using a Cox proportional hazards model.

Among 725 022 participants, 20 414 (2.8%) developed kidney outcomes during a median follow-up period of 34.6 months. Higher SBP was consistently associated with a higher incidence of kidney outcome in all PP subgroups. Although DBP had a positive linear association with the incidence of kidney outcome in low- and normal-PP subgroups, both lower (≤60 mmHg) and higher (≥101 mmHg) DBP were associated with a higher incidence of kidney outcome in the high-PP subgroup, with a U-shaped curve. Hazard ratios (95% confidence intervals) of ≤60 mmHg (reference: 61-80 mmHg in normal-PP subgroup) and ≥101 mmHg were 1.26 (1.15-1.38) and 1.86 (1.62-2.14), respectively.

In this large population-based cohort, DBP was differently associated with kidney outcome by PP level; lower DBP was significantly associated with a higher incidence of kidney outcome in the high-PP subgroup but not in the low- and normal-PP subgroups.