Insulin-treated Type 2 Diabetes Mellitus Research Articles

Factors Influencing the Subjective Health Status of Men with Insulin-treated Type 2 Diabetes Mellitus: A Secondary Analysis Using Quantile Regression Analysis

Purpose: The aim of this study was to identify the factors associated with the subjective health status by level in men with type 2 diabetes mellitus (T2DM) receiving insulin treatments. Methods: This study was a secondary analysis. A total of 120 male outpatients with insulin-treated T2DM completed in a questionnaire from July to November 2019, and results were analyzed using multiple linear and quantile regression to determine factors related to subjective health status. The 10th, 25th, 50th, 75th, and 90th conditional quantiles were considered with the aim of identifying different factors that contributed to subjective health status. Results: Subjective health status was measured by the EuroQol visual analog scale, and its mean score was 61.29±19.00 points out of 100. Through ordinary least squares analysis, family support, knowledge, self-care, and psychological insulin resistance explained 57.2% of the variance in subjective health status. Through quantile regression analysis, family support and knowledge were identified as factors significantly related factors for all percentiles, and self-care and psychological insulin resistance were the significant factors for the 50th, 75th, and 90th percentiles. Conclusion: The results of this study highlight the importance of the subjective health status of men with T2DM receiving insulin treatment, especially healthcare professionals looking for more effective intervention methods. Strategies that take into consideration various factors that explain an individual’s subjective health status have the potential to improve patient health.

Incident infection risks depending on oral antidiabetic exposure in insulin-treated type 2 diabetes patients

Dipeptidyl peptidase-4 inhibitors (DPP4is) and sodium glucose cotransporter-2 inhibitors (SGLT2is) have been speculated to have a potential to increase infection risks in type 2 diabetes mellitus (T2DM) patients. We performed a cohort study using the Korean health insurance data to investigate infection risks with each drug class relative to metformin in insulin-treated T2DM patients. After propensity score matching, we included 1,498 and 749 patients in DPP4i + insulin vs metformin + insulin and 300 and 549 patients in SGLT2i + insulin vs metformin + insulin, respectively. In stratified analyses per patient factor, none of the odds ratios (ORs) were associated with a statistical significance across respiratory, genital, and urinary tract infections (UTIs), except that of the male stratum for respiratory infections (OR 0.77, p = 0.04). With regard to SGLT2is, a higher risk of genital infections was analyzed with their use than with metformin therapy (OR 1.76, p = 0.03). In stratified analyses, the OR for genital infections remained significant in the baseline cardiovascular disease stratum (OR 2.29, p = 0.01). No increased UTI risk was detected with SGLT2is compared against metformin. In this study on insulin-receiving T2DM patients, DPP4is were not associated with increased infection risks, whereas SGLT2is led to a higher risk for genital infections, but not for UTIs, relative to metformin.

Relationship between the insulin use and stigma in type 2 diabetes mellitus

AimsThis study aimed to investigate the relationship between insulin use and stigma in Type 2 Diabetes Mellitus (T2DM). MethodsThe study was carried out in the endocrinology and metabolic disorders outpatient clinic of a state hospital between February and October 2022. The study was carried out with 154 patients, 77 of them were treated with insulin while 77 were treated with peroral antidiabetic drugs (PAD). The patient identification form and Type 2 Diabetes Stigma Assessment Scale (DSAS-2) were used for data collection. The data were analyzed by using IBM SPSS 26.0 software. ResultsDSAS-2 total score, treated differently, blame and judgment, and self-stigma subscales were higher in insulin-treated T2DM patients compared to the patients treated with PAD. There was a positive relationship between the number of daily injections and the DSAS-2 total score (r = 0.554). Multiple linear regression showed that type of the treatment, treatment duration, number of daily injections and perceived level of health were the determinants of the DSAS-2 score. ConclusionsStigma was high in insulin-treated T2DM patients and as the number of daily injections increased, the level of the perceived stigma increased. We recommend considering the high level of perceived stigma in insulin-treated T2DM patients while preparing nursing investigations.

Effect of empagliflozin versus linagliptin on body composition in Asian patients with type 2 diabetes treated with premixed insulin

Insulin therapy often increases body weight and leads to visceral fat accumulation. Progression in diabetes is also associated with accelerated loss of muscle mass. Little is known about body composition changes in type 2 diabetes mellitus (T2DM) patients on insulin therapy who use sodium–glucose cotransporter-2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors. This study examined the effect of 25 mg of empagliflozin compared with 5 mg of linagliptin for 24 weeks on body weight and body composition in patients with T2DM on premixed insulin. Body composition was assessed with bioelectrical impedance analysis. The mean difference between the linagliptin and empagliflozin groups in terms of mean body weight change from baseline to 24 weeks was − 1.80 kg (95% CI − 2.57, − 1.03). Empagliflozin also significantly reduced muscle mass (− 1.39 kg, 95% CI − 2.49, − 0.29) and total body water (− 1.07 kg, 95% CI − 1.88, − 0.27) compared with linagliptin. Compared to linagliptin, empagliflozin decreased body fat mass more from baseline to week 24, but this was not significant (− 0.31 kg, 95% CI − 1.51, 0.90). Further research on insulin-treated T2DM patients is necessary to investigate the long-term effects of SGLT2 and DPP4 inhibitors on body composition, as well as their effects on muscle strength and physical function.Trial registration: ClinicalTrials.gov no. NCT03458715, registration date: March 8, 2018.

Preadmission Insulin-Treated Type 2 Diabetes Mellitus Patients Had Increased Mortality in Intensive Care Units.

AimTo explore the clinical outcomes among preadmission insulin-treated type 2 diabetes mellitus (T2DM) in intensive care units (ICU).Patients and MethodsIn this retrospective observational study, 578 T2DM patients admitted to ICU were recruited from March 2011 to February 2021, which were composed of 528 patients treated with insulin after ICU admission (including 300 preadmission non-insulin-treated and 228 preadmission insulin-treated patients) and 50 patients treated without insulin before and after ICU admission. Clinical outcomes were compared between the groups. Variables of age (± 10 years), gender, blood glucose >10 mmol/l on ICU admission, and original comorbidities were used for matching to get the 1:1 matched cohort. The Kaplan–Meier survival curves were graphed to describe the survival trend and Cox regression analysis was performed to get adjusted hazard ratio (HR).ResultsCompared with the preadmission non-insulin-treated T2DM patients, preadmission insulin-treated T2DM patients had higher incidence of hypoglycemia [14.5% (33/228) vs 8.7% (26/300); p = 0.036]. In the 1:1 matched cohort, the preadmission insulin-treated T2DM patients had significantly increased mortality rate [30.0% (45/150) vs (16.0% (24/150)); adjusted HR, 1.68 (1.01–2.80)] than preadmission non-insulin-treated T2DM patients. Compared with T2DM patients treated without insulin before and after ICU admission, preadmission insulin-treated T2DM patients had higher mortality and longer length of ICU stay (all p < 0.05).ConclusionPreadmission insulin treatment was associated with increased mortality rate and longer length of ICU stay among T2DM patients in ICU. Preadmission insulin-treated T2DM patients might have worse clinical outcomes when they are critically ill.

Common Sense Model program on illness perceptions in patients with impaired awareness of hypoglycemia

Background: Illness perceptions are important for patients with insulin-treated type 2 diabetes mellitus (T2DM) and impaired awareness of hypoglycemia (IAH), as they determine health-related behaviors and motivations. Patients with IAH in many countries have poor illness perception, and there is a paucity of research exploring the effectiveness of Common Sense Model (CSM)-based interventions in this population. Objective: To investigate the effects of a CSM-based intervention program on perceptions of illness in patients with insulin-treated T2DM and IAH. Design: Quasi-randomized controlled trial. Methods: 78 patients with IAH receiving routine care were included. The intervention group (n = 39) participated in a CSM-based program, whereas the control group (n = 39) did not. Illness perceptions, coping styles, hypoglycemia fear, and awareness of hypoglycemia at baseline, 1, and 3 months were analyzed and compared between the two groups. Results: The intervention group exhibited significant improvements in consequences (β = -1.615, P = 0.032); personal control (β = −1.897, P = 0.006); treatment control (β = −1.274, P = 0.046); and positive coping style (β = 4.872, P = 0.002) at the 3-month follow-up, and timeline (β = 2.769, P = 0.004) at the 1-month follow-up. Hypoglycemia fear and awareness were not significantly improved in the intervention group compared with the control group. No intervention-related adverse events were observed. Conclusions: A CSM-based intervention program can modify illness perceptions to an extent and improve the positive coping style in patients with IAH. Impact statementNurses should conduct a CSM-based intervention program to help patients with IAH improve illness perceptions.

Conversations and Reactions Around Severe Hypoglycemia (CRASH): Japan Results From a Global Survey of People with T1DM or Insulin-Treated T2DM and Caregivers.

AimsThe CRASH study examined severe hypoglycemia (SH) experiences among people with diabetes (PWD) and caregivers across eight countries. Here we report findings from the Japan cohort, with references to data from the United Kingdom (UK) cohort.Materials and MethodsAdults with type 1 (T1DM) or insulin-treated type 2 diabetes mellitus (T2DM) and caregivers (not necessarily related) were recruited from online patient panels. Participants who had experienced at least one SH event in the past 3 years were eligible for study inclusion. Participants completed an online survey regarding their experience with SH, its treatment, and actions during and after an event.ResultsOf the 9367 PWD and caregivers from the online patient panels, 8475 participants were ineligible and a total of 53 Japanese participants (35 T1DM, 9 T2DM, 9 caregivers) completed the survey. Most SH incidents occurred at home and were unattended by a healthcare provider. For T1DM, 29% of Japan PWD and 13% of the UK PWD called an ambulance during an SH event; of these, 90% (Japan) and 50% (UK) were transported to hospital. Glucagon use was low (3% Japan and 10% UK for T1DM). Japanese respondents reported emotional impacts of SH, including feeling scared (86% T1DM, 56% T2DM), unprepared (63% T1DM, 78% T2DM), and helpless (60% T1DM, 33% T2DM). Despite the emotional burden, most PWD did not immediately discuss their SH event with a healthcare provider, with the majority (75% T1DM, 71% T2DM) waiting until their next doctor’s appointment.ConclusionConversations around SH between healthcare providers and PWD appear to be insufficient in Japan. An emotional burden of SH was reported by PWD and caregivers. Education regarding the prevention of SH and available treatment options may reduce SH events and improve treatment preparation, while alleviating PWD concerns.

M6A methylation-mediated elevation of SM22αinhibits the proliferation and migration ofvascular smooth muscle cells and amelioratesintimal hyperplasia in type 2 diabetes mellitus.

Abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by insulin resistance facilitates intimal hyperplasia of type 2 diabetes mellitus (T2DM) and N6-methyladenosine (m6A) methylation modification mediates the VSMC proliferation. This study aimed to reveal the m6A methylation modification regulatory mechanism. In this study, m6A demethylase FTO was elevated in insulin-treated VSMCs and T2DM mice with intimal injury. Functionally, FTO knockdown elevated m6A methylation level and further restrained VSMC proliferation and migration induced by insulin. Mechanistically, FTO knockdown elevated Smooth muscle 22 alpha (SM22α) expression and m6A-binding protein IGF2BP2 enhanced SM22α mRNA stability by recognizing and binding to m6A methylation modified mRNA. In vivo studies confirmed that the elevated m6A modification level ofSM22α mRNA mitigated intimal hyperplasia in T2DM mice. Conclusively, m6A methylation-mediated elevation of SM22α restrained VSMC proliferation and migration and ameliorated intimal hyperplasia in T2DM.

Association of Insulin Therapy with Depression, Cognition and Quality of Life in Type 2 Diabetes Patients: A Cross-sectional Study

Background: Type 2 diabetes mellitus (T2DM) is linked to a significant rate of depression and cognitive impairment, according to previous studies. However, limited research has been done on the effects of diabetes treatment on depression, cognitive function, or overall quality of life (QoL). This planned study investigated into depression, cognitive function, and quality of life in T2DM patients, as well as its relationship to treatment received. To study the association of insulin therapy with depression, cognition and quality of life in T2DM patients. Methods: This was a crosssectional study that included 300 participants, comprising of 150 T2DM patients and 150 healthy individuals. The Patient health questionnaire and the Mini-mental state examination were used to measure depression and cognitive function, respectively. QoL was assessed using the Short-Form 36 (SF-36) questionnaire. Based on the type of treatment, all of the patients were divided into two subgroups: oral hypoglycemic medications (OHAs) and insulin. Results: The study included 300 participants, including T2DM patients (n=150) and healthy controls (n=150). In individuals with T2DM, the chances of mild (aOR 2.21, 95 % Ci 1.16-4.20; p=0.016) and severe (aOR 4.32, 95 % Ci 1.27-14.67; p=0.019) depression was higher. T2DM patients were also more likely to have cognitive impairment (aOR 2.86, 95 % Ci 1.16-6.99; p=0.021). Patients taking insulin had a substantially increased risk of depression (OR 2.127, 95 % Ci 1.070-4.228, p=0.036). Insulin-treated patients exhibited considerably poorer QoL ratings. Conclusion: The research illustrates that insulin therapy has a negative impact on depression and QoL in T2DM patients. As a result, it is recommended that insulin-treated T2DM patients require psychological assistance. In such cases, it is advised that measures to enhance QoL be implemented.

Type 2 diabetes and neonatal hypoglycemia: role of route of delivery and insulin infusion

Objective To compare the rate of neonatal hypoglycemia among newborns delivered by individuals with Type 2 diabetes mellitus (T2DM) in two clinical scenarios: who attempted vaginal delivery vs. had a planned cesarean delivery (CD); who had intrapartum insulin infusion vs. who did not. Methods This was a retrospective cohort study of individuals with insulin-treated T2DM who had non-anomalous singleton pregnancy and delivered at a single tertiary center (March 2012 and May 2018). Individuals with chronic renal failure, proliferative retinopathy, or major congenital anomalies were excluded. The primary outcome was neonatal hypoglycemia (blood glucose < 40 mg/dl <24 h of age or < 50 mg/dl >24 h of age). Secondary outcomes included neonatal outcomes. Multivariable Poisson regression models with robust error variance were used to examine the association between groups and the primary outcome. Adjusted relative risk (aRR) and 95% confidence intervals (CI) were calculated. Results Of 233 individuals with T2DM, 215 (92.2%) met the inclusion criteria, of whom 95 (44%) attempted vaginal delivery and 120 (56%) had a planned CD. Individuals who labored had a higher gestational age at delivery (36.6 vs. 35.8 weeks, p = .005), and higher blood glucose levels upon admission (125 vs 103, p < .001) compared to those with a planned CD. After adjustment for potential confounders, there was no difference in risk of neonatal hypoglycemia between the groups (41.2 vs 44.1%, aRR 1.05, 95% CI = 0.75–1.45). Among those who attempted vaginal delivery, 34 (35.8%) required insulin infusion. There was no difference in the risk of neonatal hypoglycemia (aRR = 0.79, 95% CI = 0.45–1.37) between newborns delivered by individuals who required insulin infusion and those who did not. Conclusion Over 40% of newborns delivered by individuals with insulin-dependent T2DM had hypoglycemia; however, there was no significant difference in the risk of hypoglycemia, irrespective of the route of delivery and the use of insulin infusion.

Insulin-Induced Skin Lipohypertrophy in Type 2 Diabetes: a Multicenter Regional Survey in Southern Italy.

IntroductionLipohypertrophies (LHs) due to incorrect insulin injection techniques have been described in the literature for decades. Their rate averages 38%, but this is still controversial because of the vast range reported by different publications, most of which fail to describe the selected detection protocol and therefore are not entirely reliable. We still need to identify the real LH rate, and only consistently using a standardized method in a large cohort of insulin-treated (IT) patients make this possible.MethodsOur group performed thorough clinical skin examinations on patients suffering from type 2 diabetes mellitus (T2DM): 1247 IT T2DM outpatients were examined according to a standardized protocol, previously published elsewhere, as well as an ultrasound scan of the same skin areas to assess the degree of concordance between the two methods and to evaluate the demographic, clinical, and behavioral risk factors (RF) as well as metabolic consequences of identified LHs.ResultsThe concordance between the two methods was 99%. Identified risk factors for LHs were needle reuse, failure to rotate injection sites, and ice-cold insulin injections. High HbA1c values, wide glycemic variability, and longstanding proneness to hypoglycemia with a high rate of ongoing hypoglycemic events proved to be significantly associated with LHs, too; the same applied to cardiovascular and renal complications as well as to living alone and being retired.ConclusionsBased on a strict well-structured methodology, our data confirmed what has already been reported in the literature on factors leading to, or associated with, LHs and, for the first time in adults, indicated cryotrauma from ice-cold insulin injections and specific social conditions as factors facilitating LH occurrence. HCPs should therefore plan a yearly clinical examination of all injection sites to improve patient quality of life through better glucose control and a reduced rate of hypoglycemic events.Trial RegistrationTrial registration no. 127-11.01.2019, approved by the Scientific and Ethics Committee of Campania University “Luigi Vanvitelli,” Naples, Italy.

Gravicentric approach to Type 2 Diabetes therapy. &#x0D; The success prediction. A proof-of-concept

This study is the proof-of-concept of our "Gravicentric" theory. This concept is based on several fundamental points: obesity as the main foe; rapid reversibility of the disease; as well as a new perspective on the roles different pharmacological classes play in general, and the role of insulin and GLP-1 analogs, in particular. The paper presents and discusses our experience of the implementation of insulin and GLP-1 analogs. The possibility of "insulin weaning"; the therapeutic approach for over-treated patients; and physiological dosing of insulin is also discussed therein.&#x0D; Objectives&#x0D; Primary: To evaluate the long-term efficacy of GLP-1 analogs in insulin-treated Type 2 Diabetes Mellitus (T2DM) patients.&#x0D; Secondary: To analyze which patient would most likely benefit from this combined treatment.&#x0D; Methods&#x0D; In 54 T2DM patients with a mean disease duration of 17.5 years and a mean extent of insulin therapy of 4.5 years, additional GLP-1 analogs therapy was prescribed. Mean duration of GLP-1 treatment was 25.8 months (2.15 years).&#x0D; During the intervention, clinical, biochemical, and anthropometric parameters were analyzed. Compliance, Hypoglycemia and Metabolic Index (MI) assessments were implemented.&#x0D; Results&#x0D; Mean Glycated hemoglobin (HbA1C) decreased from 9.28 1.43 to 8.54 1.4% on GLP-1 analogs, p 0.01. Total Daily dose of Insulin (TDI) showed considerable reduction: 80.6 42.7 U/day before starting GLP-1 vs.41.0 30.7 U/day on GLP-1, p 0.01. These changes were directly linked to weight loss: BMI has dropped from 35.1 4.8 kg/cm2 before, to 32.8 5.0 kg/cm2 on GLP-1 analogs, with patients losing 6.7 kg on average. Moreover, 13 (24%) participants discontinued at least one kind of insulin, while 7 (13%) stopped taking insulin completely, with simultaneous improvement in diabetes control. No clinically significant hypoglycemia was observed.&#x0D; Post-hoc, the participants were categorized according to each patients ability to reduce TDI by more than 20 U/day, and then split into two groups. Group A 34 patients (64.2%) who successfully reduced TDI; Group B 19 patients (35.8%) who failed to do so. The comparison of the two groups showed the following:&#x0D; &#x0D; Significantly larger virtually twice as large baseline TDI in Group A (97.440.4 U/day vs. 52.231.0 U/day), p 0.001.&#x0D; Very effective BMI reduction (BMI 3.3 2.4 kg/cm2 0.9 1.2 kg/cm2, p 0.001) and much better compliance (1.4 1.1 vs. 2.2 1.0, p 0.02) in Group A.&#x0D; A considerable decline of insulin requirements in group A, on GLP-1 therapy (TDI on GLP-1 was -62.4 31.9 U/day) with no TDI reduction in Group B (TDI on GLP-1 was +0.03 14.1 U/day, p 0.001).&#x0D; &#x0D; Thus, in spite of the fact that on GLP1 therapy HbA1C has declined to the same levels in both groups, patients from group A became much leaner and metabolically healthier.&#x0D; We suggest overtreatment as the critical factor of obesity in Group A.&#x0D; Conclusions&#x0D; Adding GLP-1 analogs to insulin in poorly controlled, insulin-treated T2DM patients resulted in an impressive weight (BMI) reduction with significant improvements in glucose control. This provided for a further decline in insulin resistance and insulin requirements. We suggest that the best candidate for successful GLP-1 analogs therapy is an obese, overtreated and compliant T2DM person. Changes in Metabolic Index (MI) rather than surrogate glycemic parameters (HbA1C) are better predictors of a successful T2DM therapy. Neither the duration of diabetes nor the length of insulin therapy in the past is likely to have a critical role in predicting success. These findings are proof-of-concept of our Gravicentric theory in T2DM.

Impaired Awareness of Hypoglycaemia in Insulin-treated Type 2 Diabetes Mellitus.

Patients with Type 2 Diabetes Mellitus (T2DM) may develop hypoglycemia as an adverse effect of insulin therapy. Hypoglycemia has dangerous consequences that result from neuroglycopenia and hypersecretion of counter-regulatory hormones. Patients who recognize early symptoms of hypoglycemia can initiate self-treatment and rectify the situation. Impaired Awareness of Hypoglycemia (IAH) predisposes patients to severe hypoglycemia and unconsciousness. To assess the prevalence of IAH, the intensity of hypoglycaemic symptoms, the frequency of severe hypoglycemia and factors associated with IAH in patients with insulin-treated T2DM. This is a cross-sectional study that used Clarke's and Gold's surveys to assess IAH and Edinburgh survey to assess the intensity of hypoglycemic symptoms in patients with insulin-treated T2DM (n= 388). The frequency of hypoglycemia and other data were collected by self-reporting or from medical records. The prevalence (95% confidence interval) of IAH was 17.01% (13.27%-20.75%) as determined by Clarke's method and 5.93% (3.58-8.28) by Gold's method (Odds= 3.25, p-value<0.00001). Drowsiness, hunger, sweating, tiredness, trembling and weakness, were the most intense hypoglycaemic symptoms, and 6.19% of participants reported at least one episode of severe hypoglycaemia within the past year. Regardless of classification method used, IAH is not dependent on age, gender, duration of T2DM or duration of insulin therapy (p-values>0.05). Instead, IAH is positively associated with frequency of hypoglycaemia during the previous six months (p-value<0.05) and development of severe hypoglycaemia within the past year (p-value <0.05). This study highlights large variability in IAH depending on the method used for assessment. Increased hypoglycaemia frequency may increase the prevalence of IAH and thus the development of severe hypoglycemia.

Prevalence of postprandial hyperglycaemia in basal insulin-treated patients with type 2 diabetes mellitus with controlled fasting glycaemia and elevated glycosylated haemoglobin

ObjectiveTo study the prevalence of postprandial hyperglycaemia (PPH) in type 2 diabetes mellitus (T2DM) patients treated with basal insulin, having fasting glucose < 130 mg/dL but HbA1c > 7.0% (53 mmol/mol).MethodsThis was an observational prospective multicentric study conducted in Spain. During 2 weeks, patients recorded a 6-point self-measured blood glucose profile (before and 2 h after eating) every 2 days. PPH was defined according to IDF and ADA guidelines (> 160 and > 180 mg/dL, respectively).ResultsWe included 98 patients (males: 56.1%; mean age: 64.3 ± 10.4 years) who were treated with basal insulin for at least 1 year at stable doses in the last 2 months, 88.8% of them received concomitant oral antidiabetic drugs. Overall, 95.7% (95% CI 91.6–99.8) and 93.5% (95% CI 88.6–98.5) of patients showed ≥ 1 episode of PPH according to IDF and ADA criteria respectively. PPH was more frequently observed after lunch and dinner. The proportion of patients with ≥ 40% readings in range of PPH was 59.1% (95% CI 49.1–69.1) and 40.9% (95% CI 30.9–50.9), according to IDF and ADA criteria, respectively.ConclusionsPPH is very common and should be considered a priority target in basal insulin-treated T2DM patients with elevated HbA1c despite controlled fasting glucose.

Cinaciguat in combination with insulin induces a favorable effect on implant osseointegration in type 2 diabetic rats

The osseointegration process of implant is seriously impaired in type 2 diabetes mellitus (T2DM) that causes high failure rate, and insufficiency exists in current insulin therapy, creating a demand for new bone-synergistic agent. Cinaciguat, a novel type of soluble guanylate cyclase (sGC) activator, plays a vital role in glucose metabolism, inflammation control and bone regeneration. We hypothesized that the combined application of cinaciguat and insulin could reverse poor implant osseointegration in diabetes. To test this hypothesis, streptozotocin-induced diabetic rats were placed implants in the femur, and divided into five groups: control, T2DM, cinaciguat-treated T2DM (7 μg/kg), insulin-treated T2DM (12 IU/kg), cinaciguat plus insulin combination-treated T2DM (7 μg/kg and 12 IU/kg respectively), according to different treatment received. The weight and glucose levels of rats were evaluated at fixed times, and plasma level of cyclic guanosine monophosphate (cGMP) was determined before euthanasia. Three months after therapy, the femurs were isolated for pull-out test, environmental scanning electron microscope observation, microscopic computerized tomography evaluation and various histology analysis. Results revealed that diabetic rats showed the highest blood glucose level and lowest cGMP content, which led to the worst structural damage and least osseointegration. Combined treatment could attenuate the diabetes induced hyperglycemia to be normal, restore the cGMP content, protein kinase G II (PKG II) expression, phosphodiesterase-5 (PDE5) activity and ameliorate the mechanical strength, the impaired bone microarchitecture and osseointegration to the highest level. Meanwhile, monotreatment (insulin or cinaciguat) also showed restorative effect, but less. Our findings demonstrated that the cGMP/PKG II signaling pathway activated by cinaciguat mediated the favorable effects of the combined application on improving implant fixation under T2DM condition.

Hypoglycemia incidence and awareness among insulin-treated patients with diabetes: the HAT study in Brazil

BackgroundHypoglycemia affects patient safety and glycemic control during insulin treatment of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). The Hypoglycemia Assessment Tool study in Brazil aimed to determine the proportion of patients experiencing hypoglycemic events and to characterize patient awareness and fear about hypoglycemia, among insulin-treated T1DM or T2DM patients.MethodsThis was a non-interventional, multicenter study, with a 6-month retrospective and a 4-week prospective evaluation of hypoglycemic events. Patients completed a questionnaire at baseline and at the end of the study, and also a patient diary. The answers ‘occasionally’ and ‘never’ to the question ‘Do you have symptoms when you have a low sugar level?’ denoted impaired hypoglycemia awareness. Fear was reported on a 10-point scale, from ‘not afraid at all’ to ‘absolutely terrified’.ResultsFrom 679 included patients, 321 with T1DM and 293 T2DM, median age of 33.0 and 62.0 years, 59% and 56% were female, and median diabetes duration was 15.0 and 15.0 years, respectively. Median time of insulin use was 14.0 and 6.0 years. During the prospective period, 91.7% T1DM and 61.8% T2DM patients had at least one hypoglycemic event. In the same period, 54.0% T1DM and 27.4% T2DM patients had nocturnal hypoglycemia, 20.6% T1DM and 10.6% T2DM patients had asymptomatic hypoglycemia, and severe events occurred in 20.0% and 10.3%, respectively. At baseline, 21.4% T1DM and 34.3% T2DM had hypoglycemia unawareness. The mean score of hypoglycemia fear was 5.9 ± 3.1 in T1DM and 5.4 ± 3.9 in T2DM. The most common attitude after hypoglycemic events were to increase calorie intake (60.3%) and blood glucose monitoring (58.0%) and to reduce or skip insulin doses (30.8%).ConclusionsReferred episodes of hypoglycemia were high, in both T1DM and T2DM insulin users. Patient attitudes after hypoglycemia, such as reduction in insulin and increase in calorie intake, can affect diabetes management. These findings may support clinicians in tailoring diabetes education and insulin treatment for patients with diabetes, in order to improve their glycemic control while reducing the risk of hypoglycemic events.

Cardiac Versus Non-Cardiac Related Mortality Following Percutaneous Coronary Intervention in Patients with Insulin-Treated Type 2 Diabetes Mellitus: A Meta-Analysis.

IntroductionCardiovascular mortality is a major concern for patients with type 2 diabetes mellitus (T2DM). Insulin therapy significantly contributes to a high rate of death in these patients. We have performed a meta-analysis comparing cardiac and non-cardiac-related mortality following percutaneous coronary intervention (PCI) in a sample of patients with insulin-treated type 2 diabetes mellitus (ITDM).MethodsStudies were included in the meta-analysis if: (1) they were trials or cohort studies involving patients with T2DM post-PCI; (2) the outcomes in ITDM were separately reported; and (3) they reported cardiac death and non-cardiac death among their clinical endpoints. ITDM patients with any degree of coronary artery disease were included. The analysis was carried out using RevMan version 5.3 software, and data were reported with odds ratios (OR) and 95% confidence intervals (CI) as the main parameters.ResultsA total of 4072 participants with ITDM were included, of whom 1658 participants and 2414 participants were extracted from randomized controlled trials and observational cohorts, respectively. Analysis of all data showed that death due to cardiac causes was significantly higher in patients with ITDM (OR 2.16, 95% CI 1.79–2.59; P = 0.00001). At 1 year of follow-up, cardiac death was still significantly higher compared to non-cardiac death (OR 2.39, 95% CI 1.47–3.88; P = 0.0004), and this result did not change with a longer follow-up period (3–5 years) (OR 2.09, 95% CI 1.70–2.56; P = 0.00001). Death due to cardiac causes was still significantly higher in the subpopulations of patients with everolimus-eluting stents (OR 2.31, 95% CI 1.26–4.26; P = 0.007), paclitaxel-eluting stents (OR 2.36, 95% CI 1.63–3.39; P = 0.00001), sirolimus-eluting stents (OR 2.11, 95% CI 1.67–2.67; P = 0.00001), and zotarolimus-eluting stents (OR 2.12, 95% CI 1.11–4.05; P = 0.02), respectively.ConclusionsMortality due to cardiac causes was significantly higher than that due to non-cardiac causes in patients with ITDM who had undergone PCI. The same conclusion could be drawn from analyses focused on different follow-up periods, types of coronary stents, and type of study data used.

The Effect of Sitagliptin on the Regression of Carotid Intima-Media Thickening in Patients with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation.

Background. The effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on the regression of carotid IMT remains largely unknown. The present study aimed to clarify whether sitagliptin, DPP-4 inhibitor, could regress carotid intima-media thickness (IMT) in insulin-treated patients with type 2 diabetes mellitus (T2DM). Methods. This is an exploratory analysis of a randomized trial in which we investigated the effect of sitagliptin on the progression of carotid IMT in insulin-treated patients with T2DM. Here, we compared the efficacy of sitagliptin treatment on the number of patients who showed regression of carotid IMT of ≥0.10 mm in a post hoc analysis. Results. The percentages of the number of the patients who showed regression of mean-IMT-CCA (28.9% in the sitagliptin group versus 16.4% in the conventional group, P = 0.022) and left max-IMT-CCA (43.0% in the sitagliptin group versus 26.2% in the conventional group, P = 0.007), but not right max-IMT-CCA, were higher in the sitagliptin treatment group compared with those in the non-DPP-4 inhibitor treatment group. In multiple logistic regression analysis, sitagliptin treatment significantly achieved higher target attainment of mean-IMT-CCA ≥0.10 mm and right and left max-IMT-CCA ≥0.10 mm compared to conventional treatment. Conclusions. Our data suggested that DPP-4 inhibitors were associated with the regression of carotid atherosclerosis in insulin-treated T2DM patients. This study has been registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000007396).

Comparing the adverse clinical outcomes in patients with non-insulin treated type 2 diabetes mellitus and patients without type 2 diabetes mellitus following percutaneous coronary intervention: a systematic review and meta-analysis.

BackgroundSeveral studies showed Type 2 Diabetes Mellitus (T2DM) to be associated with worse adverse clinical outcomes compared to non-T2DM (NDM) following Percutaneous Coronary Intervention (PCI). In addition, patients with insulin-treated T2DM (ITDM) showed worse clinical outcomes compared to patients with non-insulin treated T2DM (NITDM). Since NITDM and NDM have seldom been systematically analyzed, this study aimed to compare the short and long term adverse clinical outcomes observed in patients with NITDM and patients without T2DM following PCI.MethodsMedline/PubMed, EMBASE and the Cochrane library were searched for Randomized Controlled Trials (RCTs) and observational studies comparing patients with (including ITDM and NITDM) and without T2DM following PCI. Endpoints included adverse clinical outcomes reported during a short and a long term follow up period. Odd Ratios (OR) and 95% Confidence Intervals (CI) in accordance with either a fixed or a random effects model appropriately, were calculated and the pooled analyses were performed with RevMan 5.3.ResultsTwelve studies consisting of a total number of 52,451 patients (14,863 NITDM and 37,588 NDM) were included. Patients with NITDM were found to have significantly higher short-term Major Adverse Cardiac Events (MACEs) and mortality with OR: 1.63, 95% CI (1.17, 2.27); P = 0.004 and OR: 1.71, 95% CI (1.40, 2.10), P < 0.00001 respectively and higher long-term MACEs and mortality with OR: 1.25, 95% CI (1.12, 1.40), P = 0.0001 and OR: 1.32, 95% CI (1.19, 1.47), P < 0.00001 respectively compared to NDM following PCI. In addition, compared to NDM, long-term Target Vessel Revascularization (TVR) and Target Lesion Revascularization (TLR) were significantly higher in the NITDM group with OR: 1.36, 95% CI (1.18, 1.56), P < 0.0001 and OR: 1.32, 95% CI (1.10, 1.59), P = 0.003 respectively. However, even if an increased long-term stent thrombosis was observed in the NITDM group with OR: 1.13; 95% CI (0.91, 1.40), P = 0.28, the result was insignificant.ConclusionShort and long term MACEs and mortality were significantly higher in patients with NITDM compared to patients without diabetes following PCI. Revascularization also significantly favored patients without T2DM. However, stent thrombosis was not significantly different.

Comparing the Clinical Outcomes Between Insulin-treated and Non-insulin-treated Patients With Type 2 Diabetes Mellitus After Coronary Artery Bypass Surgery: A Systematic Review and Meta-analysis.

Several studies have shown coronary artery bypass surgery (CABG) to be beneficial in patients with type 2 diabetes mellitus (T2DM) and multivessel coronary artery diseases. Patients with insulin-treated T2DM (ITDM) are usually patients with poor glycemic control and are expected to suffer more complications compared with patients with non-insulin-treated T2DM (NITDM). However, the adverse clinical outcomes in patients with ITDM and NITDM after CABG are still not very clear. Hence, to solve this issue, we aim to compare the short-and long-term adverse clinical outcomes in a larger number of patients with ITDM and NITDM after CABG, respectively.Randomized controlled trials and observational studies comparing the adverse clinical outcomes such as mortality, major adverse events (MAEs), stroke, myocardial infarction, and repeated revascularization in patients with ITDM and NITDM after CABG have been searched from Medline, EMBASE, Cochrane, and PubMed databases. A short-term follow-up (≤30 days) and a long-term follow-up (≥1 year) were considered. Odds ratio (OR) with 95% confidence interval (CI) was used to express the pooled effect on discontinuous variables and the pooled analyses were performed with RevMan 5.3.Eleven studies involving a total of 64,152 patients with T2DM (23,781 patients with ITDM and 40,371 patients with NITDM) have been included in this meta-analysis. During the short-term follow-up period, patients with ITDM had a significantly higher mortality (OR: 1.47; 95% CI: 1.33–1.61, P < 0.00001) and MAEs (OR: 1.66; 95% CI: 1.48–1.87, P < 0.00001). During the long-term follow-up period, patients with ITDM still had a significantly higher rate of mortality, MAEs, and stroke (OR: 1.23, 95% CI: 1.02–1.49, P = 0.03; OR: 1.50, 95% CI: 1.07–2.12, P = 0.02; OR: 1.39, 95% CI: 1.22–1.59, P < 0.00001, respectively) after CABG. However, our results showed similar repeated revascularization rate between the ITDM and NITDM groups after CABG (OR: 1.31, 95% CI: 0.81–2.12, P = 0.27).According to this study, patients with ITDM had a significantly higher rate of mortality and MAEs compared with patients with NITDM after CABG. Stroke was also significantly higher in patients with ITDM during a long-term follow-up period. However, since the result for the long-term mortality had a higher heterogeneity as compared with the other subgroups, and because a similar revascularization rate was observed between the ITDM and NITDM groups after CABG maybe because of a limited number of patients analyzed, further studies still need to be conducted to completely solve this issue.