Effectiveness and cost-effectiveness of six GLP-1RAs for treatment of Chinese type 2 diabetes mellitus patients that inadequately controlled on metformin: a micro-simulation model.

Objective: To systematically estimate and compare the effectiveness and cost-effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) approved in China and to quantify the relationship between the burden of diabetic comorbidities and glycosylated hemoglobin (HbA1c) or body mass index (BMI). Methods: To estimate the costs (US dollars, USD) and quality-adjusted life years (QALY) for six GLP-1RAs (exenatide, loxenatide, lixisenatide, dulaglutide, semaglutide, and liraglutide) combined with metformin in the treatment of patients with type 2 diabetes mellitus (T2DM) which is inadequately controlled on metformin from the Chinese healthcare system perspective, a discrete event microsimulation cost-effectiveness model based on the Chinese Hong Kong Integrated Modeling and Evaluation (CHIME) simulation model was developed. A cohort of 30,000 Chinese patients was established, and one-way sensitivity analysis and probabilistic sensitivity analysis (PSA) with 50,000 iterations were conducted considering parameter uncertainty. Scenario analysis was conducted considering the impacts of research time limits. A network meta-analysis was conducted to compare the effects of six GLP-1RAs on HbA1c, BMI, systolic blood pressure, and diastolic blood pressure. The incremental net monetary benefit (INMB) between therapies was used to evaluate the cost-effectiveness. China's per capita GDP in 2021 was used as the willingness-to-pay threshold. A generalized linear model was used to quantify the relationship between the burden of diabetic comorbidities and HbA1c or BMI. Results: During a lifetime, the cost for a patient ranged from USD 42,092 with loxenatide to USD 47,026 with liraglutide, while the QALY gained ranged from 12.50 with dulaglutide to 12.65 with loxenatide. Compared to exenatide, the INMB of each drug from highest to lowest were: loxenatide (USD 1,124), dulaglutide (USD -1,418), lixisenatide (USD -1,713), semaglutide (USD -4,298), and liraglutide (USD -4,672). Loxenatide was better than the other GLP-1RAs in the base-case analysis. Sensitivity and scenario analysis results were consistent with the base-case analysis. Overall, the price of GLP-1RAs most affected the results. Medications with effective control of HbA1c or BMI were associated with a significantly smaller disease burden (p < 0.05). Conclusion: Loxenatide combined with metformin was identified as the most economical choice, while the long-term health benefits of patients taking the six GLP-1RAs are approximate.

Development of a computerized intervention to improve health literacy in older Hispanics with type 2 diabetes using a pharmacist supervised comprehensive medication management.

OBJECTIVE: The primary objective was to develop a computerized culturally adapted health literacy intervention for older Hispanics with type 2 diabetes (T2D). Secondary objectives were to assess the usability and acceptability of the intervention by older Hispanics with T2D and clinical pharmacists providing comprehensive medication management (CMM). MATERIALS AND METHODS: The study occurred in three phases. During phase I, an integration approach (i.e., quantitative assessments, qualitative interviews) was used to develop the intervention and ensure cultural suitability. In phase II, the intervention was translated to Spanish and modified based on data obtained in phase I. During phase III, the intervention was tested for usability/acceptability. RESULTS: Thirty participants (25 older Hispanics with T2D, 5 clinical pharmacists) were included in the study. Five major themes emerged from qualitative interviews and were included in the intervention: 1) financial considerations, 2) polypharmacy, 3) social/family support, 4) access to medication/information, and 5) loneliness/sadness. Participants felt the computerized intervention developed was easy to use, culturally appropriate, and relevant to their needs. Pharmacists agreed the computerized intervention streamlined patient counseling, offered a tailored approach when conducting CMM, and could save them time. CONCLUSION: The ability to offer individualized patient counseling based on information gathered from the computerized intervention allows for precision counseling. Future studies are needed to determine the effectiveness of the developed computerized intervention on adherence and health outcomes.

Glycemic control among patients with type 2 diabetes in a low resource setting in Rwanda: a prospective cohort study.

Introduction: diabetes is a leading cause of death, disability, and high healthcare costs, especially among patients with poor glycemic control. Providing decentralized diabetes care to patients in low-income countries remains a major challenge. We aimed to assess hemoglobin A1C (HbA1c) level of patients enrolled in primary-level non-communicable disease clinics of Rwamagana, Rwanda, and identify predictors associated with a) change in HbA1c level over a 6-month period or b) achieving HbA1c <7%. We also explored whether living in a community with a home-based care practitioner was associated with HbA1c-related outcomes. Methods: we conducted structured interviews and HbA1c testing among patients with type 2 diabetes at baseline and after six months. Multivariable linear regression and multivariable logistic regression were used. Results: hundred and thirty (130) participants enrolled at baseline, and 123 patients remained in the study after six months. At baseline, 26% of patients had HbA1c <7%. After 6-months, 37% of patients had HbA1c <7%. Factors correlated with the greatest improvements in HbA1c were having HbA1c >9% at baseline, while factors associated with having HbA1c <7% after six months included older age and having HbA1c <7% at baseline. We did not find significant associations between home-based care practitioners and improvement in HbA1c level or achieving HbA1c <7. Conclusion: the number of patients with well-controlled glycemia improved over time during this study but was still low overall. Care provided by home-based care practitioners was not associated with six-month HbA1c outcomes. Enhanced care is needed to achieve glycemia control in primary healthcare settings.

Cost-effectiveness of professional-mode flash glucose monitoring in general practice among adults with type 2 diabetes: Evidence from the GP-OSMOTIC trial.

AIM: To assess the cost-effectiveness of professional-mode flash glucose monitoring in adults with type 2 diabetes in general practice compared with usual clinical care. METHODS: An economic evaluation was conducted as a component of the GP-OSMOTIC trial, a pragmatic multicentre 12-month randomised controlled trial enrolling 299 adults with type 2 diabetes in Victoria, Australia. The economic evaluation was conducted from an Australian healthcare sector perspective with a lifetime horizon. Health-related quality of life (EQ-5D) and total healthcare costs were compared between the intervention and the usual care group within the trial period. The 'UKPDS Outcomes Model 2' was used to simulate post-trial lifetime costs, life expectancy and quality-adjusted life years (QALYs). RESULTS: No significant difference in health-related quality of life and costs was found between the two groups within the trial period. Professional-mode flash glucose monitoring yielded greater QALYs (0.03 [95% CI: 0.02, 0.04]) and a higher cost (A$3807 [95% CI: 3604, 4007]) compared with usual clinical care using a lifetime horizon under the trial-based monitoring frequency, considered not cost-effective (incremental cost-effectiveness ratio = A$120,228). The intervention becomes cost-effective if sensor price is reduced to lower than 50%, or monitoring frequency is decreased to once per year while maintaining the same treatment effect on HbA1c . CONCLUSIONS: Including professional-mode flash glucose monitoring every 3 months as part of a management plan for people with type 2 diabetes in general practice is not cost-effective, but could be if the sensor price or monitoring frequency can be reduced.

Sex Difference in the Associations among Obesity-Related Indices with Metabolic Syndrome in Patients with Type 2 Diabetes Mellitus.

Background: The aim of this study was to investigate the associations among obesity-related indices and MetS in diabetic patients, and explore sex differences in these associations. Methods: Patients with type 2 DM were included from two hospitals in southern Taiwan. The Adult Treatment Panel III criteria for an Asian population were used to define MetS. In addition, the following obesity-related indices were evaluated: waist-to-height ratio, waist-hip ratio (WHR), conicity index (CI), body mass index (BMI), body roundness index, body adiposity index, lipid accumulation product (LAP), abdominal volume index, visceral adiposity index (VAI), abdominal volume index and triglyceride-glucose index. Results: A total of 1,872 patients with type 2 DM (mean age 64.0 ± 11.3 years, 808 males and 1,064 females) were enrolled. The prevalence rates of MetS were 59.8% and 76.4% in the males and female (p < 0.001), respectively. All of the obesity-related indices were associated with MetS in both sex (all p < 0.001). LAP and BMI had the greatest areas under the receiver operating characteristic curves in both sex. In addition, the interactions between BMI and sex (p = 0.036), WHR and sex (p = 0.016), and CI and sex (p = 0.026) on MetS were statistically significant. Conclusions: In conclusion, this study demonstrated significant relationships between obesity-related indices and MetS among patients with type 2 DM. LAP and VAI were powerful predictors in both sex. The associations of BMI, WHR and CI on MetS were more significant in the men than in the women.

Association of sex-specific differences in lipoprotein(a) concentrations with cardiovascular mortality in individuals with type 2 diabetes mellitus.

BACKGROUND: Compared to individuals without type 2 diabetes mellitus, the relative increase in cardiovascular mortality is much higher in women than in men in individuals with type 2 diabetes mellitus. METHODS: We evaluated data from 7443 individuals (3792 women, 50.9%), aged 20 to 81 years, from two independent population-based investigations, SHIP-0 and MONICA/KORA S3. We analyzed the longitudinal sex-specific associations of lipoprotein(a) with cardiovascular mortality in individuals with and without type 2 diabetes mellitus using Cox regression. RESULTS: During a median follow-up of 20.5 years (136,802 person-years), 657 participants (404 men and 253 women) died of cardiovascular causes. Among individuals without type 2 diabetes mellitus, men had a significantly higher risk for cardiovascular mortality compared to women in unadjusted model and after adjustment. On the other hand, in participants with type 2 diabetes mellitus, the risk for cardiovascular mortality was not different between men and women in the unadjusted model and after adjustment for age, body mass index, low-density lipoprotein-cholesterol, fasting status and study sample (SHIP-0, MONICA/KORA S3). Further adjustment for lipoprotein(a) concentrations had no impact on the hazard ratio (HR) for cardiovascular mortality comparing men versus women in individuals without type 2 diabetes mellitus [HR: 1.94; 95% confidence interval (CI) 1.63 to 2.32; p < 0.001]. In individuals with type 2 diabetes mellitus, however, further adjustment for lipoprotein(a) led to an increased risk for cardiovascular mortality in men and a decreased risk in women resulting in a statistically significant difference between men and women (HR: 1.53; 95% CI 1.04 to 2.24; p = 0.029). CONCLUSIONS: Women are described to have a stronger relative increase in cardiovascular mortality than men when comparing individuals with and without type 2 diabetes mellitus. Higher lipoprotein(a) concentrations in women with type 2 diabetes mellitus than in men with type 2 diabetes mellitus might partially explain this finding.

Assessment of heart rate variability (HRV) in subjects with type 2 diabetes mellitus with and without diabetic foot: correlations with endothelial dysfunction indices and markers of adipo-inflammatory dysfunction.

BACKGROUND: Some studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixed population of healthy subjects of middle and advanced age. AIMS: The aim of this study was to evaluate the degree of alteration of sympathovagal balance, assessed by HRV analysis, in a cohort of patients with diabetes mellitus with diabetic foot and in control subjects without diabetic foot compared with a population of healthy subjects and the possible correlation of HRV parameters with inflammatory markers and endothelial dysfunction indices. METHODS: We enrolled all patients with diabetic ulcerative lesions of the lower limb in the Internal Medicine with Stroke Care ward and of the diabetic foot outpatient clinic of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-h ECG Holter was performed. The following time domain HRV measures were analyzed: average heart rate, square root of the mean of successive differences of NN (RMSSD), standard deviation or square root of the variance (SD), and standard deviation of the means of the NN intervals calculated over a five-minute period (SDANN/5 min). The LF/HF ratio was calculated, reactive hyperemia was evaluated by endo-PAT, and serum levels of vaspine and omentin-1 were assessed by blood sample collection. RESULTS: 63 patients with diabetic foot, 30 patients with diabetes and without ulcerative complications and 30 patients without diabetes were enrolled. Patients with diabetic ulcers showed lower mean diastolic blood pressure values than healthy controls, lower MMSE scores corrected for age, lower serum levels of omentin-1, lower RHI values, higher body weight values and comparable body height values, HF% and LF/HF ratio values. We also reported a negative correlation between the RHI value and HRV indices and the expression of increased parasympathetic activity (RMSDD and HF%) in subjects with diabetic foot and a statistically significant positive correlation with the LF/HF ratio and the expression of the sympathovagal balance. DISCUSSION: Patients with diabetic foot show a higher degree of activation of the parasympathetic system, expressed by the increase in HF values, and a lower LF/HF ratio. Our findings may corroborate the issue that a parasympathetic dysfunction may have a possible additive role in the pathogenesis of other vascular complications in subjects with diabetic foot.

A 16-year prospective cohort study to evaluate effects of long-term fluctuations in obesity indices of prediabetics on the incidence of future diabetes.

This study aimed to evaluate the patterns of changes in obesity indices over time in prediabetic subjects and to classify these subjects as either having a low, moderate, and high risk for developing diabetes in the future. This study was conducted among 1228 prediabetics. The patterns of changes in obesity indices based on three measurements including first, mean values during the follow-up period, and last visit from these indices were evaluated by using the latent Markov model (LMM). The mean (standard deviation) age of subjects was 44.0 (6.8) years and 73.6% of them were female. LMM identified three latent states of subjects in terms of change in all anthropometric indices: a low, moderate, and high tendency to progress diabetes with the state sizes (29%, 45%, and 26%), respectively. LMM showed that the probability of transitioning from a low to a moderate tendency to progress diabetes was higher than the other transition probabilities. Based on a long-term evaluation of patterns of changes in obesity indices, our results reemphasized the values of all five obesity indices in clinical settings for identifying high-risk prediabetic subjects for developing diabetes in future and the need for more effective obesity prevention strategies.

Association of Real-time Continuous Glucose Monitoring With Glycemic Control and Acute Metabolic Events Among Patients With Insulin-Treated Diabetes.

Importance: Continuous glucose monitoring (CGM) is recommended for patients with type 1 diabetes; observational evidence for CGM in patients with insulin-treated type 2 diabetes is lacking. Objective: To estimate clinical outcomes of real-time CGM initiation. Design, Setting, and Participants: Exploratory retrospective cohort study of changes in outcomes associated with real-time CGM initiation, estimated using a difference-in-differences analysis. A total of 41 753 participants with insulin-treated diabetes (5673 type 1; 36 080 type 2) receiving care from a Northern California integrated health care delivery system (2014-2019), being treated with insulin, self-monitoring their blood glucose levels, and having no prior CGM use were included. Exposures: Initiation vs noninitiation of real-time CGM (reference group). Main Outcomes and Measures: Ten end points measured during the 12 months before and 12 months after baseline: hemoglobin A1c (HbA1c); hypoglycemia (emergency department or hospital utilization); hyperglycemia (emergency department or hospital utilization); HbA1c levels lower than 7%, lower than 8%, and higher than 9%; 1 emergency department encounter or more for any reason; 1 hospitalization or more for any reason; and number of outpatient visits and telephone visits. Results: The real-time CGM initiators included 3806 patients (mean age, 42.4 years [SD, 19.9 years]; 51% female; 91% type 1, 9% type 2); the noninitiators included 37 947 patients (mean age, 63.4 years [SD, 13.4 years]; 49% female; 6% type 1, 94% type 2). The prebaseline mean HbA1c was lower among real-time CGM initiators than among noninitiators, but real-time CGM initiators had higher prebaseline rates of hypoglycemia and hyperglycemia. Mean HbA1c declined among real-time CGM initiators from 8.17% to 7.76% and from 8.28% to 8.19% among noninitiators (adjusted difference-in-differences estimate, -0.40%; 95% CI, -0.48% to -0.32%; P < .001). Hypoglycemia rates declined among real-time CGM initiators from 5.1% to 3.0% and increased among noninitiators from 1.9% to 2.3% (difference-in-differences estimate, -2.7%; 95% CI, -4.4% to -1.1%; P = .001). There were also statistically significant differences in the adjusted net changes in the proportion of patients with HbA1c lower than 7% (adjusted difference-in-differences estimate, 9.6%; 95% CI, 7.1% to 12.2%; P < .001), lower than 8% (adjusted difference-in-differences estimate, 13.1%; 95% CI, 10.2% to 16.1%; P < .001), and higher than 9% (adjusted difference-in-differences estimate, -7.1%; 95% CI, -9.5% to -4.6%; P < .001) and in the number of outpatient visits (adjusted difference-in-differences estimate, -0.4; 95% CI, -0.6 to -0.2; P < .001) and telephone visits (adjusted difference-in-differences estimate, 1.1; 95% CI, 0.8 to 1.4; P < .001). Initiation of real-time CGM was not associated with statistically significant changes in rates of hyperglycemia, emergency department visits for any reason, or hospitalizations for any reason. Conclusions and Relevance: In this retrospective cohort study, insulin-treated patients with diabetes selected by physicians for real-time continuous glucose monitoring compared with noninitiators had significant improvements in hemoglobin A1c and reductions in emergency department visits and hospitalizations for hypoglycemia, but no significant change in emergency department visits or hospitalizations for hyperglycemia or for any reason. Because of the observational study design, findings may have been susceptible to selection bias.

Assessment of erythrocyte morphology in patients with type 2 diabetes mellitus: a pilot study of electron microscopy-based analysis in relation to healthy controls

Background/aim: The present study aimed to assess erythrocyte morphology in newly diagnosed type 2 diabetes mellitus patients using scanning electron microscopy. Materials and methods: In total, 30 patients admitted to endocrine outpatient clinics were included in the study. The patients were divided into two groups according to their fasting blood glucose levels: type 2 diabetes mellitus (n = 15, fasting blood glucose levels ≥ 126 mg/dL) and control (n = 15, fasting blood glucose levels < 99 mg/dL). The patient's demographic characteristics, haemoglobin A1c levels, and scanning electron microscopy findings regarding erythrocyte morphology were recorded. Results: There was no significant difference between the control and type 2 diabetes mellitus group in terms of the participants' age (51.13 ± 8.53 vs. 50.33 ± 8.72 years, p = 0.8) and the male/female ratio (9/6 vs. 9/6). In the control group, discocytes were abundant, echinocytes were rare, and spherocytes were absent. On the other hand, discocytes were less common and echinocyte-shaped erythrocytes were more common in the type 2 diabetes mellitus group than in the control group. In addition, spherocytes were detected in the type 2 diabetes mellitus group. Moreover, the diameter of discocytes was significantly lower (p = 0.014), and blood glucose and haemoglobin A1c levels were significantly higher (p < 0.05 for both) in the type 2 diabetes mellitus group than in the control group. Conclusion: Our findings indicate that high glucose levels in type 2 diabetes mellitus patients lead to significant alterations in erythrocyte morphology, including decreased erythrocyte deformability and the formation of echinocytes and spherocytes due to eryptosis. The possibility of decreased erythrocyte deformability due to excessive eryptosis may disturb microcirculation in newly diagnosed, treatment-naïve type 2 diabetes mellitus patients who do not have any complications.

Assessment of safety and tolerability of remogliflozin etabonate (GSK189075) when administered with total daily dose of 2000 mg of metformin.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are characterized by an elevated glycemic index and are at a higher risk for complications such as cardiovascular disease, nephropathy, retinopathy and peripheral neuropathy. Normalization of glycemic index can be achieved by dosing combinations of metformin with other anti-diabetic drugs. The present study (Clintrials number NCT00519480) was conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of remogliflozinetabonate, an SGLT2 inhibitor, withdoses (500 mg and 750 mg BID) greater than the commercial dose (100 mg BID)in combination with metformin with minimum daily dose of 2000 mg given in two divided doses. METHODS: This was a randomized, double-blinded, repeat dose study in 50 subjects with T2DM. The study was conducted in three phases; run-in, randomization, and treatment. All subjects were on a stable metformin dosing regimen. Cohort 1 subjects were randomly allocated to receive either remogliflozin etabonate 500 mg BID or placebo BID (2:1) in addition to metformin. Cohort 2 subjects were administered with either remogliflozin etabonate 750 mg BID or placebo BID (2:1) in addition to metformin for 13 days. All the subjects were assessed for safety (adverse events, lactic acid levels, vital signs, electrocardiogram [ECG]), pharmacokinetic evaluation, and pharmacodynamics (Oral Glucose Tolerance Testing) parameters. RESULTS: Co-administration of remogliflozin etabonate and metformin was well tolerated in all subjects during the observation period. There were no severe or serious adverse events (SAEs) and no increase in lactic acid concentration was reported during the study. The statistical results showed that concomitant administration of remogliflozin etabonate, either 500 mg or 750 mg BID, with metformin had no effect on the pharmacokinetics of metformin. The accumulation ratios, Day 13 vs. Day 1, for AUC values of remogliflozin etabonate and its metabolites were all very close to 1, indicating no accumulation in plasma concentrations of remogliflozin etabonate and its metabolites. Mean glucose values from baseline and glucose and insulin values following oral glucose tolerance test (OGTT) were decreased in all treatment groups. CONCLUSION: Co-administration of doses of remogliflozin etabonate (500 mg BID or 750 mg BID) greater than the commercial dose (100 mg BID) with metformin (2000 mg BID) was shown to be safe and effective during the observation period. TRIAL REGISTRATION: ClinicalTrials.gov , NCT00519480 . Registered:22 August 2007.

Assessment of risk factors for bone fractures in patients with type 2 diabetes mellitus: A study in Saudi Arabia.

BACKGROUND AND AIMS: This study aimed to estimate the prevalence of bone fractures and analyze their associated risk factors in people with and without type 2 diabetes (T2D) in Saudi Arabia. METHODS: This study was conducted among 1188 people (581 type 2 diabetes) in Prince Sultan Military Medical City, Riyadh, Saudi Arabia. In addition to the demographic variables, glycated hemoglobin (HbA1c), creatinine, estimated glomerular filtration rate (eGFR), use of teriparatide, presence of rheumatoid arthritis, presence of chronic obstructive pulmonary disease (COPD), Bone mineral density (BMD), Trabecular Bone Score (TBS) and Fracture Risk using the Fracture Risk Assessment Tool (FRAX) were also collected. RESULTS: There were 1188 people (mean age 66.5 ± 8.7yrs) included in this study, of which 1068 (89.9%) were female, and 120 (10.1%) were male. A total of 112 (9.4%) individuals had a fracture history. Female, use of teriparatide, TBS (partially degraded and degraded), FRAX with TBS (MOF), and FRAX with TBS (Hip fx) were identified as independent risk factors for fracture in the whole study population. Teriparatide use and FRAX with TBS (MOF) were observed as independent risk factors for fracture in the non-diabetic population, whereas age, creatinine, eGFR, teriparatide, osteopenia, osteoporosis, TBS (partially degraded, degraded), FRAX with TBS (MOF), FRAX with TBS (Hip fx) were determined as independent risk factors for fracture among patients with diabetes. CONCLUSION: Patients with T2D were observed to have a higher risk for fractures. The findings of the study highlight the requirement for fracture prevention strategies in patients with diabetes.

Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study.

BACKGROUND: Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures. METHODS: In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders. RESULTS: Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation. CONCLUSIONS: Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.

Effects of different aerobic exercise training on glycemia in patients with type 2 diabetes: A protocol for systematic review and meta analysis.

BACKGROUND: Type 2 diabetes is an emergent worldwide health crisis, and rates are growing globally. Aerobic exercise is an essential measure for patients with diabetes, which has the advantages of flexible time and low cost. Aerobic exercise is a popular method to reduce blood glucose. Due to the lack of randomized trials to compare the effects of various aerobic exercises, it is difficult to judge the relative efficacy. Therefore, we intend to conduct a network meta-analysis to evaluate these aerobic exercises. METHODS: According to the retrieval strategies, randomized controlled trials on different aerobic exercise training will be obtained from China National Knowledge Infrastructure, WanFang, SinoMed, PubMed, Web of Science, EMBASE, and Cochrane Library, regardless of publication date or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool will be used to evaluate the quality of the literature. The network meta-analysis will be performed in Markov Chain Monte Carlo method and carried out with Stata14 and OpenBUGS software. Ultimately, the evidentiary grade for the results will be evaluated. RESULTS: Eighteen literatures with a total of 1134 patients were included for the meta-analysis. In glycemia assessment, Tennis (standard mean difference = 3.59, credible interval 1.52, 5.65), had significantly better effects than the named control group. Tennis (standard mean difference = 3.50, credible interval 1.05, 5.59), had significantly better effects than the named Taiji group. CONCLUSION: All together, these results suggest that tennis may be the best way to improve blood glucose in patients with type 2 diabetes. This study may provide an excellent resource for future control glycemia and may also serve as a springboard for creative undertakings as yet unknown.

Cost-effectiveness analysis for HbA1c test intervals to screen patients with type 2 diabetes based on risk stratification.

BACKGROUND: The best HbA1c test interval strategy for detecting new type 2 diabetes mellitus (T2DM) cases in healthy individuals should be determined with consideration of HbA1c test characteristics, risk stratification towards T2DM and cost effectiveness. METHODS: State transition models were constructed to investigate the optimal screening interval for new cases of T2DM among each age- and BMI-stratified health individuals. Age was stratified into 30-44-, 45-59-, and 60-74-year-old age groups, and BMI was also stratified into underweight, normal, overweight and obesity. In each model, different HbA1c test intervals were evaluated with respect to the incremental cost-effectiveness ratio (ICER) and costs per quality-adjusted life year (QALY). Annual intervals (Japanese current strategy), every 3 years (recommendations in US and UK) and intervals which are tailored to each risk stratification group were compared. All model parameters, including costs for screening and treatment, rates for complications and mortality and utilities, were taken from published studies. The willingness-to-pay threshold in the cost-effectiveness analysis was set to US $50,000/QALY. RESULTS: The HbA1c test interval for detecting T2DM in healthy individuals varies by age and BMI. Three-year intervals were the most cost effective in obesity at all ages-30-44: $15,034/QALY, 45-59: $11,849/QALY, 60-74: $8685/QALY-compared with the other two interval strategies. The three-year interval was also the most cost effective in the 60-74-year-old age groups-underweight: $11,377/QALY, normal: $18,123/QALY, overweight: $12,537/QALY-and in the overweight 45-59-year-old group; $18,918/QALY. In other groups, the screening interval for detecting T2DM was found to be longer than 3 years, as previously reported. Annual screenings were dominated in many groups with low BMI and in younger age groups. Based on the probability distribution of the ICER, results were consistent among any groups. CONCLUSIONS: The three-year screening interval was optimal among elderly at all ages, the obesity at all ages and the overweight in 45-59-year-old group. For those sin the low-BMI and younger age groups, the optimal HbA1c test interval could be longer than 3 years. Annual screening to detect T2DM was not cost effective and should not be applied in any population.

Cardiovascular risk assessment by coronary artery calcium score in subjects with maturity-onset diabetes of the young caused by glucokinase mutations.

AIMS: Maturity-Onset Diabetes of the Young (MODY) caused by glucokinase (GCK) mutations is characterized by lifelong mild non-progressive hyperglycemia, with low frequency of coronary artery disease (CAD) compared to other types of diabetes. The aim of this study is to estimate cardiovascular risk by coronary artery calcification (CAC) score in this group. MATERIALS AND METHODS: Twenty-nine GCK-MODY cases, 26 normoglycemic controls (recruited among non-affected relatives/spouses of GCK mutation carriers), and 24 unrelated individuals with type 2 diabetes were studied. Patients underwent CAC score evaluation by computed tomography and were classified by Agatston score ≥ or < 10. Framingham Risk scores of CAD in 10 years were calculated. RESULTS: Median [interquartile range] CAC score in GCK-MODY was 0 [0,0], similar to controls (0 [0,0], P = 0.49), but lower than type 2 diabetes (39 [0, 126], P = 2.6 × 10-5). A CAC score ≥ 10 was seen in 6.9% of the GCK group, 7.7% of Controls (P = 1.0), and 54.2% of individuals with type 2 diabetes (P = 0.0006). Median Framingham risk score was lower in GCK than type 2 diabetes (3% vs. 13%, P = 4 × 10-6), but similar to controls (3% vs. 4%, P = 0.66). CONCLUSIONS: CAC score in GCK-MODY is similar to control individuals from the same family and/or household and is significantly lower than type 2 diabetes. Besides demonstrating low risk of CAD in GCK-MODY, these findings may contribute to understanding the specific effect of hyperglycemia in CAD.

Can a monthly exenatide extended release regimen provide a therapeutic and cost benefit?

Exenatide is used to treat type 2 diabetes mellitus. The current regimen is a 2 mg extended release (ER) weekly injection. The aim of our study was to prove the efficacy of exenatide ER if administered once-monthly. The proposed monthly dose was based on an Excel simulation using pharmacokinetic parameters extracted using Plot Digitizer® (version 2.6.8) from Cirincione et al. (2017), as well as accounting for the exenatide ER formulation characteristics, in vivo and in vitro exenatide stability. A PBPK model of exenatide molecule was developed using (Simcyp® version 19) based on data from in vitro and clinical PK studies. The model was used to confirm the Excel simulation findings of the effectiveness of exenatide ER monthly in maintaining the plasma level above the minimum effective concentration (MEC). Our simulation from Excel and Simcyp® showed that the drug plasma levels of the once monthly ER dose maintained a steady state concentration (Css ) above the MEC. The simulated Excel plasma level ranged from Cmin to Cmax of 60-130ng/L, respectively. The exenatide compound was successfully modeled and used to predict the Css of the ER monthly dose. The Simcyp® simulated Css of the ER was 117 ng/L. A monthly exenatide ER dose provides a plasma level within the therapeutic range. This new proposed dose has a significant pharmacoeconomic benefit and could well improve patient adherence.

Emerging technologies for the management of type 2 diabetes mellitus.

Diabetes mellitus is a global health problem affecting 422 million people worldwide, of which 34.2 million live in the United States alone. Complications due to diabetes can lead to considerable morbidity and mortality related to both microvascular and macrovascular disease. While glycosylated hemoglobin testing is the standard test utilized to evaluate glycemic control, emerging targets like "time in range" and "glycemic variability" often provide more accurate assessments of glycemic fluctuations and have implications for diabetes complications and quality of life. Patients with diabetes face considerable burdens of self-care including frequent glucose monitoring, multiple insulin injections, dietary management, and the need to track daily activities, all of which lead to reduced adherence and psychological burnout. From the provider perspective, limited patient data and access to self-management tools lead to treatment inertia and a reduced ability to help patients achieve and maintain their glycemic goals. In the past few decades, there have been considerable advances in treatment-based technology and technological applications designed to help reduce patient burden and provide tools for better self-management. These advances make real-time clinical data available for clinicians to make necessary changes in treatment regimens. In this review, we discuss the latest emerging technologies available for the management of people with type 2 diabetes mellitus.

Intervention by clinical pharmacists can improve blood glucose fluctuation in patients with diabetes and acute myocardial infarction: A propensity score-matched analysis.

Acute phase hyperglycemia and exaggerated glucose fluctuation may be associated with poor outcomes in diabetic patients after acute myocardial infarction (AMI). This study aimed to determine whether intervention by clinical pharmacists can mitigate blood glucose and glucose fluctuations in these fragile patients. This retrospective study enrolled patients with diabetes and AMI, from 1 January 2019 to 30 June 2020 in our institution. Blood glucose and glucose fluctuations were calculated before and after the pharmacist's intervention and between patients who underwent intervention and those who did not. Propensity score matching (PSM) was used to reduce the impact of patient characteristics on the results. A total of 170 patients were included in our primary analysis, including 29 patients who received the pharmacist intervention and 141 patients who did not. After the pharmacist's intervention, blood glucose (fasting blood glucose-FBG, from 11.9 to 9.8; postprandial blood glucose-PBG, from 15.3 to 13.2; mean blood glucose-BG, 14.5 to 12.3 mmol/L; p < .001), and glucose fluctuations (standard deviation of blood glucose-SDBG, from 3.8 to 3.0, mmol/L, p = .005) were significantly improved. Before PSM, no clear effects were found in intervention versus nonintervention patients, in terms of blood glucose and glucose fluctuation indicators, except for FBG (9.3 vs. 8.0. mmol/L, p = .005). Further analysis indicated a high incidence of FBG <7.8 mmol/L in nonintervention versus intervention patients (51.5% vs. 27.6%, p = .003). After PSM, a significant reduction in blood glucose fluctuation (SDBG, 3.0 vs. 4.1, p = .031; PBGE, 2.1 vs. 4.1, p = .017; LAGE, 4.7 vs. 7.2, mmol/L, p = .004), and PBG (11.1 vs. 13.0, mmol/L, p = .048) was observed in the intervention group than in the nonintervention group. The clinical pharmacist intervention contributed to improved outcomes, specifically, in reducing blood glucose fluctuations and potential hypoglycemia risk.

Cost-Effectiveness of the New 2018 American College of Physicians Glycemic Control Guidance Statements Among US Adults With Type 2 Diabetes.

OBJECTIVES: This study aims to estimate the national impact and cost-effectiveness of the 2018 American College of Physicians (ACP) guidance statements compared to the status quo. METHODS: Survey data from the 2011-2016 National Health and Nutrition Examination were used to generate a national representative sample of individuals with diagnosed type 2 diabetes in the United States. Individuals with A1c <6.5% on antidiabetic medications are recommended to deintensify their A1c level to 7.0% to 8.0% (group 1); individuals with A1c 6.5% to 8.0% and a life expectancy of <10 years are recommended to deintensify their A1c level >8.0% (group 2); and individuals with A1c >8.0% and a life expectancy of >10 years are recommended to intensify their A1c level to 7.0% to 8.0% (group 3). We used a Markov-based simulation model to evaluate the lifetime cost-effectiveness of following the ACP recommended A1c level. RESULTS: 14.41 million (58.1%) persons with diagnosed type 2 diabetes would be affected by the new guidance statements. Treatment deintensification would lead to a saving of $363 600 per quality-adjusted life-year (QALY) lost for group 1 and a saving of $118 300 per QALY lost for group 2. Intensifying treatment for group 3 would lead to an additional cost of $44 600 per QALY gain. Nationally, the implementation of the guidance would add 3.2 million life-years and 1.1 million QALYs and reduce healthcare costs by $47.7 billion compared to the status quo. CONCLUSIONS: Implementing the new ACP guidance statements would affect a large number of persons with type 2 diabetes nationally. The new guidance is cost-effective.