Enhancing Choices Regarding the Administration of Insulin Among Patients With Diabetes Requiring Insulin Across Countries and Implications for Future Care

There are a number of ongoing developments to improve the care of patients with diabetes across countries given its growing burden. Recent developments include new oral medicines to reduce cardiovascular events and death. They also include new modes to improve insulin administration to enhance adherence and subsequent patient management thereby reducing hypoglycaemia and improving long-term outcomes. In the case of insulins, this includes long-acting insulin analogues as well as continuous glucose monitoring (CGM) systems and continuous subcutaneous insulin infusion systems, combined with sensor-augmented pump therapy and potentially hybrid closed-loops. The benefits of such systems have been endorsed by endocrine societies and governments in patients with Type 1 diabetes whose HbA1c levels are not currently being optimised. However, there are concerns with the low use of such systems across higher-income countries, exacerbated by their higher costs, despite studies suggesting their cost-effectiveness ratios are within accepted limits. This is inconsistent in higher-income countries when compared with reimbursement and funding decisions for new high-priced medicines for cancer and orphan diseases, with often limited benefits, given the burden of multiple daily insulin injections coupled with the need for constant monitoring. This situation is different among patients and governments in low- and low-middle income countries struggling to fund standard insulins and the routine monitoring of HbA1c levels. The first priority in these countries is to address these priority issues before funding more expensive forms of insulin and associated devices. Greater patient involvement in treatment decisions, transparency in decision making, and evidence-based investment decisions should help to address such concerns in the future.

The impact of depression diagnosis on diabetes and lifetime hyperglycaemia

Aims The aim of this study was to evaluate longitudinal associations between the mean and variability of HbA1c levels in individuals with type 2 diabetes (T2D) and major depressive disorder (MDD). Methods Individuals with T2D from the UK Biobank with linked primary care records were analysed. An HbA1c measurement within +/- 6-months of T2D diagnosis was taken as baseline, with subsequent HbA1c measurements used as the outcome in generalised least squares regression to evaluate longitudinal associations with a three-level MDD diagnosis variable (MDD controls, pre-T2D MDD cases and post-T2D MDD cases). Results Using 7,968 T2D individuals, we show that MDD has utility in explaining mean HbA1c levels (p=6.53E-08). This is attributable to MDD diagnosis interacting with baseline T2D medication (p=3.36E-04) and baseline HbA1c (p=2.66E-05), but not with time- when all else is equal, the temporal trend in expected HbA1c did not differ by MDD diagnosis. However, joint consideration with baseline T2D medication showed that each additional medication prescribed was associated with a +4 mmol/mol (2.5%) increase in expected HbA1c across follow up for post-T2D MDD cases, relative to pre-T2D MDD cases and MDD controls. Furthermore, variability in HbA1c increased across time for post-T2D MDD cases but decreased for MDD controls and pre-T2D MDD cases. Conclusions These findings suggest closer monitoring of individuals with both T2D and MDD is essential to improve their diabetic control, particularly for those who develop MDD after T2D diagnosis.

Reversal of Graves’ Disease with a Whole Foods Plant Based Diet: A Case Report

The benefits of a whole-food, plant-based diet (WFPBD) include, but are not limited to, improvement of cardiovascular health, decreased inflammation, as well as enhanced endocrine system function. We present the case of a 51-year-old pre-diabetic female with a 22-year history of Graves’ disease who reversed her conditions following the ini- tial 28-week WFPBD period. In this time, she was able to reduce her thyroid stimu- lating immunoglobulin (TSI) and hemoglobin A1c (HbA1c) levels and discontinue methimazole and cetirizine intake. It was also found that maintaining vitamin D levels are beneficial for promoting a more balanced immune response to help lower thyroid antibodies.

Duration of Type II DM, HbA1C Levels, TNF-α and IL-10 as Risk Factors for Level Charcot Joint Foot and Ankle in Type II DM Patients

Introduction: Type II Diabetes Mellitus has complications including disorders of the musculoskeletal system or what is often called diabetic charcot joint or charcot neuroarthropathy. Various risk factors are thought to increase the incidence of Charcot joint foot and ankle. Various studies have been made to assess these risk factors with the aim of reducing the occurrence of these complications. Material and Methods: The study used an analytical observational design with a case study and control approach to determine whether Type II DM II ≥ 10 years, HbA1c levels II ≥ 7%, TNF-α levels II ≥ 1.0 ng/L and IL-10 levels ≤ 255 pg/mL as factors. risk of Charcot joint foot and ankle in Type II DM patients. Where the sample involves 24 case groups and 24 control groups. Then a descriptive analysis was performed, bivariate inferential analysis using the chi-square test and an assessment of the risk factor odds ratio (OR). Then multivariate analysis was performed to assess the strength of the influence of risk factors using logistic regression test Results: There is a significant difference between Type II DM II ≥ 10 years, HbA1c levels II ≥ 7%, TNF-α levels II ≥ 1.0 ng/L, and IL-10 levels ≤ 255 pg/mL which are risk factors for the occurrence of charcot joint foot and ankle in Type II DM patients. The duration of type II DM II ≥ 10 years had the strongest relationship while IL-10 ≤ 255 pg/mL had the weakest relationship for the occurrence of Charcot joint foot and ankle in Type II DM patients. Conclusion: Increased duration of Type II DM, HbA1c level and TNF-α level above certain level and low IL-10 amount are risk factor for Charcot joint foot and ankle in Type II DM patients, with the duration of type II DM being the strongest risk factor. Key words: Diabetes mellitus type II, charcot joint foot and ankle, risk factors.

Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

<b>Objective:</b> Current guidelines recommend prescribing SGLT-2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. <p><b>Methods:</b> In the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial 17,160 patients with type 2 diabetes were randomized to dapagliflozin or placebo for a median follow up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population, and with dapagliflozin vs. placebo in HbA1c subgroups were studied by Cox regression models.</p> <p><b>Results:</b> In the overall population, increasing HbA1c was associated with higher risk of cardiovascular death or hospitalization for heart failure (CVD/HHF), major adverse cardiovascular events (MACE; CVD, myocardial infarction, ischemic stroke) and of the cardiorenal outcome (adjusted HR [95% CI] 1.12 [1.06-1.19], 1.08 [1.04-1.13] and 1.17 [1.11-1.24] per 1% increase respectively). Elevated HbA1c was associated with an increased risk for MACE and for the cardiorenal outcome significantly more in patients with multiple risk factors (MRF), vs. patients with established ASCVD (P-interaction 0.0064 and 0.0093 respectively). Dapagliflozin led to a decrease in the risk of CVD/HHF, HHF and the cardiorenal outcome vs. placebo with no heterogeneity by baseline HbA1c (P-interaction >0.05).</p> <p><b>Conclusions</b>: High HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c<7%.</p>

Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

<b>Objective:</b> Current guidelines recommend prescribing SGLT-2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. <p><b>Methods:</b> In the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial 17,160 patients with type 2 diabetes were randomized to dapagliflozin or placebo for a median follow up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population, and with dapagliflozin vs. placebo in HbA1c subgroups were studied by Cox regression models.</p> <p><b>Results:</b> In the overall population, increasing HbA1c was associated with higher risk of cardiovascular death or hospitalization for heart failure (CVD/HHF), major adverse cardiovascular events (MACE; CVD, myocardial infarction, ischemic stroke) and of the cardiorenal outcome (adjusted HR [95% CI] 1.12 [1.06-1.19], 1.08 [1.04-1.13] and 1.17 [1.11-1.24] per 1% increase respectively). Elevated HbA1c was associated with an increased risk for MACE and for the cardiorenal outcome significantly more in patients with multiple risk factors (MRF), vs. patients with established ASCVD (P-interaction 0.0064 and 0.0093 respectively). Dapagliflozin led to a decrease in the risk of CVD/HHF, HHF and the cardiorenal outcome vs. placebo with no heterogeneity by baseline HbA1c (P-interaction >0.05).</p> <p><b>Conclusions</b>: High HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c<7%.</p>

Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

OBJECTIVE Current guidelines recommend prescribing SGLT2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. RESEARCH DESIGN AND METHODS In the Dapagliflozin Effect on Cardiovascular Events trial (DECLARE-TIMI 58), 17,160 patients with type 2 diabetes were randomly assigned to dapagliflozin or placebo for a median follow-up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population and with dapagliflozin versus placebo in HbA1c subgroups were studied by Cox regression models. RESULTS In the overall population, higher baseline HbA1c was associated with a higher risk of cardiovascular death or hospitalization for heart failure (HHF); major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and ischemic stroke; and cardiorenal outcomes (adjusted hazard ratios 1.12 [95% CI 1.06–1.19], 1.08 [1.04–1.13], and 1.17 [1.11–1.24] per 1% higher level, respectively). Elevated HbA1c was associated with a greater increased risk for MACE and cardiorenal outcomes in patients with multiple risk factors (MRF) than in established ASCVD (P-interaction = 0.0064 and 0.0093, respectively). Compared with placebo, dapagliflozin decreased the risk of cardiovascular death/HHF, HHF, and cardiorenal outcomes, with no heterogeneity by baseline HbA1c (P-interaction &gt; 0.05). CONCLUSIONS Higher HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c &lt;7%.

Association between glycemic control and risk of venous thromboembolism in diabetic patients: a nested case–control study

Background Previous studies suggested an elevated risk of venous thromboembolism (VTE) among patients with type 2 diabetes mellitus (T2DM), with a possible sex difference. The impact of glycemic control on the risk of VTE is unclear. Our objective was to analyze the association between glycemic control and the risk of unprovoked (idiopathic) VTE in men and women with T2DM. Methods We conducted a nested case–control analysis (1:4 matching) within a cohort of patients with incident T2DM between 1995 and 2019 using data from the CPRD GOLD. We excluded patients with known risk factors for VTE prior to onset of DM. Cases were T2DM patients with an unprovoked treated VTE. The exposure of interest was glycemic control measured as HbA1c levels. We conducted conditional logistic regression analyses adjusted for several confounders. Results We identified 2′653 VTE cases and 10′612 controls (53.1% females). We found no association between the HbA1c level and the risk of VTE in our analyses. However, when the most recent HbA1c value was recorded within 90 days before the index date, women with HbA1c levels > 7.0% had a 36–55% increased relative risk of VTE when compared to women with HbA1c > 6.5–7.0%. Conclusions Our study raises the possibility that female T2DM patients with HbA1c levels > 7% may have a slightly higher risk for unprovoked VTE compared to women with HbA1c levels > 6.5–7.0%. This increase may not be causal and may reflect differences in life style or other characteristics. We observed no effect of glycemic control on the risk of VTE in men.

The effectiveness of an intervention designed based on health action process approach on diet and medication adherence among patients with type 2 diabetes: a randomized controlled trial

Background Diabetes is a major cause of worldwide morbidity and mortality. Diet and medication non-adherence are common among individuals with diabetes, making glycemic control difficult to attain. This study aimed to evaluate an intervention designed based on Health Action Process Approach (HAPA) to improve adherence to diet and medication among patients with type 2 diabetes in Tehran, Iran. Methods The study was a randomized controlled trial. A total of 248 patients with type 2 diabetes who had low diet and medication adherence were randomly allocated into two intervention (n = 124) and control (n = 124) groups. Intervention group received educational intervention during three months. HAPA constructs, diet and medication adherence, and Hemoglobin A1c (HbA1c) levels were assessed at baseline, one month and six months after the intervention. Mixed Model Analysis was used to compare between and within group changes in the outcomes. Results There was a statistically significant improvement in HbA1c levels after six months (7.77 ± 1.36% vs. 8.07 ± 1.52%, 95% CI, p < 0.001). Diet and medication adherence, intention, task self-efficacy, coping self-efficacy, recovery self-efficacy, action and coping planning, barriers, benefits and perceived social support were significantly improved one month and six months after the intervention (p < 0.001). Conclusion Our intervention designed based on health action process approach led to improvements in diet and medication adherence, and HbA1c among the patients within one and six months. Trial registration: IRCT, IRCT20151208025431N4. Registered 10 March 2018, https://fa.irct.ir