Early Initiation Of Insulin Therapy Research Articles

Real-World Outcomes of Individualized Targeted Therapy with Insulin Glargine 300Units/mL in Insulin-Naïve Korean People with Type2 Diabetes: TOBE Study.

The TOujeo BEyond glucose control (TOBE) study evaluated clinical outcomes with insulin glargine 300units/mL (Gla-300) in insulin-naïve Korean people with type2 diabetes mellitus (T2DM) in a real-world setting. This 24-week, prospective, non-interventional, multicenter, open-label, single-arm, observational study included adults aged ≥ 20years with T2DM suboptimally controlled with oral hypoglycemic agents and/or glucagon-like peptide1 receptor agonists who require basal insulin. Eligible participants were assigned to either general target glycated hemoglobin (HbA1c < 7%) or individualized target groups as per physician's discretion considering guidelines and participants' characteristics. The primary endpoint was the proportion of participants achieving the HbA1c target (individualized or general) at 24weeks. Among 369 participants, 19.5% (72/369) of participants achieved the HbA1c target at week24; 37.5% (33/88) in the individualized and 13.9% (39/281) in the general target group. In both target groups, similar reductions in fasting plasma glucose and body weight were observed, with low incidence of hypoglycemia, and T2DM duration was significantly shorter in participants who did versus those who did not achieve the target HbA1c (individualized target group: 9.6 ± 8.0 versus 13.1 ± 8.4years, P = 0.0454; general target group: 10.2 ± 8.6 versus 12.8 ± 7.4years, P = 0.0378). This study showed that initiation of insulin therapy with Gla-300 in people with T2DM using an individualized approach is more effective in achieving an HbA1c target. Moreover, earlier initiation of insulin therapy in people with suboptimally controlled T2DM may increase the success rate of glycemic control. A graphical abstract is available with this article.

Early onset type 2 diabetes mellitus: an update.

The incidence and prevalence of type 2 diabetes mellitus (T2DM) in young individuals (aged <40 years) have significantly increased in recent years, approximating two to threefold increase in the respective rates. Numerous risk factors including severe obesity, family history, ethnicity, maternal diabetes or gestational diabetes, and female sex contribute to a younger age of onset. In terms of pathogenesis, impaired insulin secretion is the key operating mechanism, alongside with ectopic adiposity-related insulin resistance. T2DM diagnosis in a young adult requires the exclusion of type 1 diabetes mellitus (T1DM), latent autoimmune diabetes of adults (LADA) and maturity-onset diabetes of the young (MODY). The establishment of such diagnosis is critical for prognosis, because early-onset T2DM is associated with rapid deterioration in pancreatic β-cell secretory function leading to earlier initiation of insulin therapy. Furthermore, mortality and lifetime risk of developing complications, especially microvascular, is increased in these patients compared to both later-onset T2DM and T1DM patients; also, the latter are often developed earlier in the course of disease. The management of early-onset T2DM follows the same guidelines as in later-onset T2DM; yet patients aged 18-39 years are underrepresented in the big clinical trials on which the development of guidelines is based. Finally, young people with T2DM face significant challenges associated with social determinants, which compromise their adherence to therapy and induce diabetes distress. Future research focusing on the pathogenesis of β-cell decline and complications, as well as on specific treatment shall lead to better understanding and management of early-onset T2DM.

Clinical features of the course of overt diabetes mellitus during pregnancy

Objective: to analyze the features of diagnosis, course and outcomes of pregnancy in women with manifest diabetes mellitus.Materials and methods: the study included 19 delivery medical records of women with MDM (manifest diabetes mellitus during pregnancy) and 500 records of women with GDM (gestational diabetes mellitus).Results: Th irteen women out of nineteen were diagnosed with MDM in the fi rst half of pregnancy. Th e average level of glycemia at the onset of the disease was 9,3±3,0 mmol/l. Mean HbA1c was 7,2±1,1%, which signifi cantly exceeded this indicator in GDM. All women with MDM required insulin therapy, while in the group of women with GDM insulin therapy was used in 27.8% of cases. MDM women showed increased rates of preeclampsia (36,8%) compared to GDM women (15%). Fetal macrosomia was more common in MDM women (36.8%) than in GDM women (17%).Conclusion: Th e high frequency of obstetric and perinatal complications of MDM during pregnancy requires the early detection of hyperglycemia and the prompt initiation of insulin therapy. Screening for carbohydrate metabolism disorders at the fi rst prenatal visit and early initiation of insulin therapy reduce maternal and perinatal mortality.

Genotype-phenotype correlations and response to glucose lowering therapy in subjects with HNF1β associated diabetes.

Molecular defects of hepatic nuclear factor 1β (HNF1β) are associated with multiorgan disease (renal disease, pancreatic hypoplasia, and genital tract anomalies) in addition to diabetes. We examined the phenotypic features, insulin secretory response to glucose, and response to treatment in subjects with HNF1β-MODY (MODY 5). Twelve subjects with HNF1β-MODY were phenotyped in detail. A 2-h oral glucose tolerance test was performed to establish insulin secretory response with glucose, insulin and C-peptide measurements taken at baseline and 30min intervals. Clinical follow-up occurred bi-annually. Ten of 12 subjects had diabetes with mean age of onset of 30.2 ± 15.5years, fasting glucose of 9.7 ± 4.6mmol/L and HbA1c of 60.9 ± 17.1mmol/mol (7.7 ± 1.6%). Renal and/or pancreatic morphological abnormalities were found in 9 subjects. Mean fasting C-peptide (0.5 ± 0.4nmol/L) and AUC C-peptide (1.5 ± 1.0nmol/L/120min) were reducedin our cohort with 4 subjects demonstrating marked insulin deficiency. OGIS was reduced at 290.2 ± 67.0mlmin-1m-2. 6/10 subjects were on insulin therapy at initial diagnosis and 8/10 at last clinical follow-up. Mean insulin dose at last clinical follow-up was 0.45 ± 0.23units/kg/day. 5 subjects on insulin were trialled on sulphonylurea therapy, and none was successfully weaned off insulin. Diagnosing HNF1β-MODY in a diabetes clinic is challenging due to its variable phenotype and variable age of onset. β-Cell dysfunction and insulin resistance contribute to diabetes in HNF1β-MODY. No subjects successfully transitioned to sulphonylurea. Early initiation of insulin therapy would be suitable to achieve glycaemic control. This emphasizes the importance of genetic testing for monogenic forms of diabetes to guide personalized treatment.

Diabetes and Prediabetes in Children With Cystic Fibrosis: A Systematic Review of the Literature and Recommendations of the Italian Society for Pediatric Endocrinology and Diabetes (ISPED).

Cystic fibrosis related diabetes (CFRD) is a comorbidity of cystic fibrosis (CF) that negatively impacts on its clinical course. Prediabetes is an important predictor of either CFRD development and unfavorable prognosis of CF in both pediatric and adult patients. International guidelines recommend insulin only in case of CFRD diagnosis. Whether early detection and treatment of prediabetes may contribute to improve the clinical course of CF is still debated. A subgroup of pediatric diabetologists of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED) performed a systematic review of the literature based on predefined outcomes: impact of pre-diabetes on clinical outcomes and on the risk of developing CFRD; diagnosis of diabetes and pre-diabetes under 10 years of age; effectiveness of therapy on glycemic control, impact of therapy on pulmonary function and nutritional status. Thirty-one papers were selected for the analysis data presented in these papers were reported in tables sorted by outcomes, including comprehensive evidence grading according to the GRADE approach. Following the grading of the quality of the evidence, the entire ISPED diabetes study group achieved consensus for the Italian recommendations based on both evidence and clinical experience. We concluded that in patients with CF, prediabetes should be carefully considered as it can evolve into CFRD. In patients with CF and prediabetic conditions, after complete evaluation of the OGTT trend, glucometrics, glycemic values measured during pulmonary exacerbations and/or steroid therapy, early initiation of insulin therapy could have beneficial effects on clinical outcomes of patients with CF and prediabetes.

Early Initiation of Insulin Therapy in Newly Diagnosed Patients with Type 2 Diabetes and Exploring the Legacy Effect—A Single-arm Prospective Observational Study

Early Initiation of Insulin Therapy in Newly Diagnosed Patients with Type 2 Diabetes and Exploring the Legacy Effect—A Single-arm Prospective Observational Study

650-P: Safety and Effectiveness of Recombinant Human Insulin Insugen in Real-World Clinical Setting

Background: As the burden of diabetes is increasing dramatically, the demand of insulin is also on rise, affordable access to insulin remains a challenge, particularly in Low and Mid income countries. For that reason, recombinant human insulin (rHI) formulations are considered to be effective alternatives to insulin analogues in countries with limited healthcare systems and resources. Continuing patient education and support programmes with rHI are critical role players in improving the access and overall disease management. Objective: This is a non-interventional study to observe the safety and effectiveness of Recombinant Human insulin in a real world population with type 2 (T2DM) diabetes mellitus from Indian perspective. Methodology: Out of 10426 diabetes patients who were enrolled in patient support program i.e “Insulin Therapy Assistance Program (iTAP)”, 5691 patients were initiated with various formulations of rHI (Insugen R, N, 30/70 and 50/50). Insulin therapy was initiated in T2DM patients with A1C &amp;gt; 7%. HbA1c, FPG and PPG values were recorded at baseline and follow up of 3, 6 and 9 months. Results: The Figure 1, 2, 3 depict the baseline and follow up of FBG, PPG and HbA1c respectively. Figure 1. Change in FPG (*p&amp;lt;0.05). Figure 2. Change in PPG (*p&amp;lt;0.05). Figure 3. Change in HbA1c (*p&amp;lt;0.05). Conclusion: In the current study, various formulations of rHI were well tolerated and resulted in significant reduction of HbA1c, FPG and PPG when aided with patient support program. Considering the economic impact of diabetes patients in taking insulins, human insulin become an alternative option in comparison to analogues which are expensive. Early initiation of insulin therapy can prevent or delay diabetes complications. Access to affordable insulin therapy is the key success factor while considering Insulin Therapy. Disclosure P. Raj: Employee; Self; Biocon. P. J: None. D.C. Mathew: None. C. Biswas: None. S. Nethra: None.

Best Practices and Tools for Titrating Basal Insulins: Expert Opinion from an Indian Panel via the Modified Delphi Consensus Method.

AimTo develop an evidence-based expert group consensus document on the best practices and simple tools for titrating basal insulins in persons with type 2 diabetes mellitus (T2DM).BackgroundGlycemic control is suboptimal in a large proportion of persons with T2DM, despite insulin therapy, thereby increasing the risk of potentially severe complications. Early initiation of insulin therapy and appropriate dose titration are crucial to achieving glycemic targets. Attitudes and practices among healthcare professionals (HCPs) and perceptions about insulin therapy among persons with diabetes contribute largely to suboptimal glycemic control. Improving HCP–patient communication, encouraging the use of additional educational tools, and providing support for the titration process to increase confidence, both at the initiation visit and at home, facilitate the optimization of dose titration. In Indian settings, specific guidelines and a consensus statement are lacking on the optimal insulin initiation dose, frequency of dose titration, and basal insulin profile needed to achieve optimal titration. In clinical practice, physicians and persons with diabetes often do not adhere to the titration algorithms that currently exist for the purpose of achieving optimal titration as they perceive these to be very cumbersome. In this context, a group of experts met at an advisory board meeting and arrived at a consensus on best practices for the titration of basal insulin in persons withT2DM in India, using the modified Delphi methodology.Review ResultsAfter a review of evidence and further discussions, the expert group provided recommendations on insulin initiation dose, ideal period for titration in practice, titration regimen for use in practice, basal insulin profile for titration, and choosing a self-monitoring blood glucose schedule for titration.ConclusionsIn the management of T2DM, insulin can be effectively titrated by following a few simple recommendations. The use of second-generation basal insulin aids in mitigating the risk of hypoglycemic events. The implementation of a simplified titration regimen is crucial to achieving glycemic targets and long-term treatment goals.

Reason for refusal of insulin therapy among type 2 diabetes mellitus patients in primary care clinic in Bangalore.

Background:Early initiation of insulin therapy and thereby the better control of blood sugar levels has shown reduction in complications. Although insulin therapy has been demonstrated to be efficacious, its initiation is often delayed due to multiple factors including the refusal of insulin therapy by the patients. This study aims to explore the reasons for the refusal of insulin therapy in a resource-constrained primary care setting in an urban slum in India.Materials and Methods:We included 148 patients who required insulin therapy but refused. A semi-structured questionnaire was administered by a primary care physician. Chi-square test was done to test the association between demographic factors and the reasons for refusal. P < 0.05 was considered as significant.Results:The mean age of the patients was 49.53 (SD+/-9.8) years. Majority (40.5%) of the patients had diabetes for 6-10 years, and most of them were living with their families (89.9%) and 77% of them were dependent on their family for their financial and physical needs. Financial constraint was the most common reason for reason (74.3%) followed by afraid of pain (68.9%) and fear of dependency (57.4). Gender, occupation, and duration of diabetes and witnessing insulin administration were significantly associated with stigma related to insulin therapy.Conclusion:Financial constraint is one of the key factors as patients have to buy insulin out of pocket and are not covered by insurance. Government initiatives to reduce and monitor the cost of the insulin would be of great benefit to the patients in this setting.

Influence of Timing of Insulin Initiation on Long-term Glycemic Control in Japanese Patients with Type 2 Diabetes: A Retrospective Cohort Study.

Objective Delays in insulin initiation can lead to the development of complications in the management of type 2 diabetes. Methods In this study, the effects of the timing of insulin initiation on glycemic control in patients with type 2 diabetes were evaluated retrospectively. Changes in the HbA1c levels of 237 patients were analyzed after insulin initiation. Results The patients were divided into 4 groups according to the duration of diabetes at the time of insulin initiation: ≤3 years, 4 to 6 years, 7 to 9 years, or ≥10 years. Patients with a diabetes duration of ≤3 years were more frequently hospitalized at the time of insulin initiation, had a higher HbA1c level before insulin initiation and a lower HbA1c level at 1 year after insulin initiation and exhibited significant decreases in HbA1c at 1, 3, or 5 years after insulin initiation than those in the other 3 groups with longer durations of diabetes. In the group receiving 4 insulin injections per day, the reduction in HbA1c after 5 years of treatment was larger in patients with a diabetes duration at the time of insulin initiation of ≤3 years than in those with a duration of 7 to 9 years or ≥10 years. Conclusion Our results suggested that an earlier initiation of insulin therapy was crucial for sustaining glycemic control in Japanese patients with type 2 diabetes, particularly in those with a history of obesity or receiving multiple insulin injections daily.

530-P: Early Insulin Initiation in T2DM Is Associated with Prevention of eGFR Decline and Lower Insulin Dose Requirements

Early initiation of insulin therapy often remains contentious due to various patient and physician-related barriers. Insulin is delayed by several years despite high A1c and is the foremost reason for costly future complications. In addition, the problem of early aggressive use of insulin depleting drugs causes β-cell fatigue leading to "brittle diabetes" and higher insulin dose requirements. In this observational cohort study, a comparison has been made between early insulin initiators (EII) (within 7-8 years of diabetes onset) and late insulin initiators (LII) (&amp;gt;8 years of onset), in terms of progression of CKD (eGFR decline), if any. A total of 200 subjects in each arm were matched at baseline for T2DM duration (16.78±4.32 year), BP, BMI, HbA1c and presence of co-morbid illnesses. Both groups were closely followed-up through our Diabetes Tele Management System based health care model that have previously shown to be successful in safely achieving glycemic targets compared to conventional models of care. A paired t test was done for analyzing the eGFR decline within each arm. EII arm required a significantly lower total daily dose of insulin (TDD) (average of 9 units/day) to maintain glycemic control throughout than the LII arm (average of 30 units/day). The decline in eGFR was significant in the LII arm, whereas in the EII arm, eGFR was maintained throughout. Change in A1c was also significant. Disclosure J. Kesavadev: None. R. Warrier: None. L. Ramachandran: None. A. Shankar: None. A. David: None. N.A. Ajai: None. G. Sanal: None. K. Thampiraj: None. G. Krishnan: None. S. Jothydev: None.

Barriers to the early initiation of Insulin therapy among diabetic patients coming to diabetic clinics of tertiary care hospitals.

Background and Objective:Initiation of Insulin therapy during earlier stages has proved to significantly improve health outcomes among diabetics in comparison to oral medications. Not only patients but physicians are also often resistant to early initiation of insulin therapy. The objective was to assess misconceptions and barriers to early initiation of insulin therapy among diabetic patients coming to a diabetic clinic.Methods:This cross sectional study was conducted on 300 patients selected by convenience sampling arriving in Diabetes Outdoor Clinics of Mayo and Services Hospitals, Lahore during August 2017 to May 2018. The data was entered and analyzed by using SPSS version 17.Results:Out of 300 patients included in study, 39% (n= 117) were males and 61% (n=183) were females. The mean age of the participants at presentation was 48.46±13.15 years with a range of 13 to 80 years. Study participants considered it embarrassing to inject insulin in public place (p-value 0.01). The fear associated with lifelong commitment to insulin therapy once it is started, was also found statistically significant (p-value 0.001)particularly in subjects who have long duration of DM (>5 years).Conclusion:Perceptions of diabetic patients about insulin therapy are still barriers to early initiation of therapy and tend to prevail in Pakistan and around the globe.

Second-Generation Insulin Analogues - a Review of Recent Real-World Data and Forthcoming Head-to-Head Comparisons.

Insulin analogues play a key role in the effective management of type 2 diabetes. However, there are several behavioural barriers to appropriate early initiation of insulin therapy, despite compelling evidence supporting the benefits of this strategy in those patients for whom oral anti-diabetes agents provide insufficient control. The development of second-generation insulin analogues (insulin glargine 300 U/mL and insulin degludec) has provided physicians with agents that can provide comparable glycaemic control to first-generation insulin, but with a reduced risk of hypoglycaemia and modes of action suited to once-daily regimens. These characteristics may help overcome patient and physician concerns about early insulin use in disease management. To date, there have been no head-to-head comparisons of second-generation insulins: here we consider recent real-world evidence and the forthcoming direct comparison in the BRIGHT randomised controlled study, as presented at the recent 11th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD) 2018.

When and how to Use Ultralong-Acting Basal Insulin in T2Dm

Current treatment guidelines for T2DM note that basal insulin can be used throughout the progression of T2DM: •At diagnosis ( 15. Garber A.J. Abrahamson M.J. Barzilay J.I. et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2016 executive summary. Endocr Pract. 2016; 22: 84-113 Abstract Full Text Full Text PDF PubMed Google Scholar , 16. American Diabetes Association, Standards of medical care in diabetes--2016. Diabetes Care. 2016; 39: S1-S111 PubMed Google Scholar , 40. Owens D.R. Clinical evidence for the earlier initiation of insulin therapy in type 2 diabetes. Diabetes Technol Ther. 2013; 15: 776-785 Crossref PubMed Scopus (53) Google Scholar ). Insulin is the treatment of choice for newly diagnosed patients with severely elevated A1C and symptoms of hyperglycemia ( 15. Garber A.J. Abrahamson M.J. Barzilay J.I. et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2016 executive summary. Endocr Pract. 2016; 22: 84-113 Abstract Full Text Full Text PDF PubMed Google Scholar , 16. American Diabetes Association, Standards of medical care in diabetes--2016. Diabetes Care. 2016; 39: S1-S111 PubMed Google Scholar ). Other patients who are especially likely to benefit from initial insulin therapy include treatment-naïve individuals with hyperglycemic symptoms and A1C >8.5% and patients with latent autoimmune diabetes ( 40. Owens D.R. Clinical evidence for the earlier initiation of insulin therapy in type 2 diabetes. Diabetes Technol Ther. 2013; 15: 776-785 Crossref PubMed Scopus (53) Google Scholar ). Notably, with appropriate dose adjustment, insulin can be used in any patient, even those with hepatic or renal impairments or other comorbidities preventing the use of other classes of antihyperglycemic agents ( 1. U.S. Food and Drug Administration. Drugs@ FDA: FDA approved drug products. http://www.accessdata.fda.gov/Scripts/cder/ DrugsatFDA/Date accessed: August 6, 2016 Google Scholar ). •In combination with noninsulin agents ( 1. U.S. Food and Drug Administration. Drugs@ FDA: FDA approved drug products. http://www.accessdata.fda.gov/Scripts/cder/ DrugsatFDA/Date accessed: August 6, 2016 Google Scholar , 15. Garber A.J. Abrahamson M.J. Barzilay J.I. et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2016 executive summary. Endocr Pract. 2016; 22: 84-113 Abstract Full Text Full Text PDF PubMed Google Scholar , 16. American Diabetes Association, Standards of medical care in diabetes--2016. Diabetes Care. 2016; 39: S1-S111 PubMed Google Scholar , 41. Diabetes Care. 2016; 39: 973-981 Crossref PubMed Scopus (67) Google Scholar ). The American Association of Clinical Endocrinologists (AACE) recommends adding insulin when patients with T2DM are unable to attain glycemic control using ≥2 noninsulin agents ( 15. Garber A.J. Abrahamson M.J. Barzilay J.I. et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2016 executive summary. Endocr Pract. 2016; 22: 84-113 Abstract Full Text Full Text PDF PubMed Google Scholar ), and the American Diabetes Association (ADA) recommends basal insulin as one of several options to consider in patients unable to attain glycemic control with metformin ( 16. American Diabetes Association, Standards of medical care in diabetes--2016. Diabetes Care. 2016; 39: S1-S111 PubMed Google Scholar ). Using noninsulin agents such as metformin and a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in combination with basal insulin is also associated with more favorable effects on glycemic variability—a risk factor for hypoglycemia—than combining metformin, basal insulin, and prandial insulin ( 41. Diabetes Care. 2016; 39: 973-981 Crossref PubMed Scopus (67) Google Scholar ). •In long-duration T2DM ( 15. Garber A.J. Abrahamson M.J. Barzilay J.I. et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2016 executive summary. Endocr Pract. 2016; 22: 84-113 Abstract Full Text Full Text PDF PubMed Google Scholar , 42. Lebovitz H.E. Insulin secretagogues: old and new. Diabetes Rev. 1999; 7: 139-153 Google Scholar ). The loss of β-cell function is inevitable as T2DM progresses: if patients live long enough, they will eventually require insulin therapy ( 43. Turner R.C. Cull C.A. Frighi V. Holman R.R. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999; 281: 2005-2012 Crossref PubMed Scopus (1983) Google Scholar , 44. Reach G. Le Pautremat V. Gupta S. Determinants and consequences of insulin initiation for type 2 diabetes in France: analysis of the National Health and Wellness Survey. Patient Prefer Adherence. 2013; 7: 1007-1023 Crossref PubMed Scopus (23) Google Scholar ).

Determinants and consequences of insulin initiation for type 2 diabetes in France: analysis of the National Health and Wellness Survey

BackgroundThe aim of the study was to identify the intrinsic patient characteristics and extrinsic environmental factors predicting prescription and use and, more specifically, early initiation (up to 5 years of disease duration) of insulin for type 2 diabetes in France. A secondary objective was to evaluate the impact of insulin therapy on mental and physical quality of life and patient adherence.MethodsThe data used in this study were derived from the 2008, 2010, and 2011 France National Health and Wellness Survey. This survey is an annual, cross-sectional, self-administered, Internet-based questionnaire among a nationwide representative sample of adults (aged 18 years or older). Of the total of 45,958 persons recruited in France, 1,933 respondents (deduped) were identified as diagnosed with type 2 diabetes. All unique respondents from the three waves, currently using insulin or oral bitherapy or tritherapy at the time of assessment, were included in this analysis.ResultsEarly (versus late) initiation of insulin therapy was 9.9 times more likely to be prescribed by an endocrinologist or diabetologist than by a primary care physician (P < 0.0001). Younger age at diagnosis and current smoking habits were significant predictors of early (versus late) insulin initiation (odds ratio [OR] 1.031, 95% confidence interval [CI] 1.005–1.059, P = 0.0196, and OR 2.537, 95% CI 1.165–5.524, P = 0.0191, respectively). Patients with a yearly income ≥€50,000 were less likely to be put on insulin early (P = 0.0399). A link between insulin prescription and complications was shown only in univariate analysis. Mental quality of life was lower in patients on early (versus late) insulin, but only in patients with diabetes-related complications. Insulin users (versus oral bitherapy or tritherapy users) had 3.0 times greater odds of being adherent than uncontrolled oral bitherapy or tritherapy users (OR 2.983, 95% CI 1.37–6.495, P = 0.0059).ConclusionThis study confirms the role of specialists in early initiation of insulin, and the data presented herein reflect the fact that early initiation is more frequent in younger patients, patients with diabetes-related complications, and current smokers, and less frequent in patients with a higher income. Moreover, we observed that being treated with insulin was not associated with deterioration in quality of life, and insulin-treated patients were more often adherent than uncontrolled oral bitherapy or tritherapy users. These data suggest that doctors’ concerns about patient adherence and detrimental effects on quality of life should not be a barrier to their decision regarding early initiation of insulin therapy. Due to the nature of this cross-sectional survey (eg, inability to assess treatment flow), further research is needed to confirm its findings.

The effectiveness and safety of the supplementation of therapy with oral hypoglycemic agents by basal insulin in the patients with type 2 diabetes mellitus. Results of the SOLOS observational program

The results of numerous clinical investigations carried out during the last years provide convincing evidence of the high effectiveness and safety of early initiation of insulin therapy. Of special interest are the studies conducted under conditions of real clinical practice. One of them is the Russian SOLOS observational program designed to evaluate the influence of intensification of the treatment of type 2 diabetes mellitus with oral hypoglycemic agents (OHA) supplemented by using insulin glargine in the patients who failed to be adequately compensated by OHA therapy alone. Another objective of this program was to find out the opinion of the patients and physicians about the SoloStar pen employed for injecting insulin glargine. The data concerning 1309 patients at the mean age of 59.5±8.8 years with type 2 diabetes mellitus and the mean duration of the disease 6.9±5.0 years were available for the analysis. The overwhelming majority of the patients presented with severe decompensation of carbohydrate metabolism, the mean fasting blood glucose level being 10.7±2.4 mmol/l and the HbA1c level varying from 7.2 to 18.2% (mean 9.6±1.5%). Supplementation of OHA therapy with insulin glargine caused the significant reduction of the HbA1c level to 8.1±1.0% (p&lt;0.001) within 3 months after the onset of the combined treatment. The HbA1c level fell down to 7.2±0.9% (p&lt;0.001) after 6 months 40.6% of the patients had HbA1c at the level below 7%. Fasting blood glucose levels decreased to 7.4±1.4 mmol/l and 6.3±1.0 mmol/l (p&lt;0.001) at 3 and 6 months after the onset of insulin administration respectively. The number of daytime and nocturnal hypoglycemic episodes under effect of insulin glargine injections significantly decreased by the end of the study. Severe hypoglycemic episodes suffered initially by 8 (0.5%) patients totally disappeared 6 months after the initiation of the combined therapy. Most patients did not need hospitalization after supplementation of OHA treatment with insulin. The results of combined therapy with the use of disposable SoloStar pens were positively assessed by the overwhelming majority of both the patients and the physicians involved in the study.

Clinical evidence for the earlier initiation of insulin therapy in type 2 diabetes.

The natural history of type 2 diabetes mellitus (T2DM) is a relentless progression of β-cell failure and dysregulation of β-cell function with increasing metabolic derangement. Insulin remains the only glucose-lowering therapy that is efficacious throughout this continuum. However, the timing of introduction and the choice of insulin therapy remain contentious because of the heterogeneity of T2DM and the well-recognized behavioral and therapeutic challenges associated with this mode of therapy. Nevertheless, the early initiation of basal insulin has been shown to improve glycemic control and affect long-term outcomes in people with T2DM and is a treatment strategy supported by international guidelines as part of an individualized approach to chronic disease management. The rationale for early initiation of insulin is based on evidence demonstrating multifaceted benefits, including overcoming the glucotoxic effects of hyperglycemia, thereby facilitating "β-cell rest," and preserving β-cell mass and function, while also improving insulin sensitivity. Independent of its effects on glycemic control, insulin possesses anti-inflammatory and antioxidant properties that may help protect against endothelial dysfunction and damage resulting in vascular disease. Insulin therapy and the achievement of good glycemic control earlier in T2DM provide long-term protection to end organs via "metabolic memory" regardless of subsequent treatments and degree of glycemic control. This is evidenced from long-term observations continuing from trials such as the United Kingdom Prospective Diabetes Study. As such, early initiation of insulin therapy may not only help to avoid the effects of prolonged glycemic burden, but may also positively alter the course of disease progression.

Predictors of achieving HbA1c

Background:Early initiation of insulin therapy has widely been associated with numerous benefits, including improved glycaemic control and reduced long-term risk of developing microvascular diseases. Biphasic insulins offer a convenient option for insulin initiation, addressing both basal and postprandial insulin requirements with one injection, making them relatively simple for patients to dose. Development of biphasic insulin aspart (BIAsp) has further offered improved postprandial glycaemic control and lower rates of nocturnal and major hypoglycaemia than biphasic human insulin.Methods:The safety and efficacy of the 30/70 rapid-acting/intermediate-acting formulation of BIAsp (BIAsp 30) in patients with type 2 diabetes was examined in the IMPROVE study, a 26-week, international, observational trial. In this subanalysis, baseline clinical factors that predicted treatment success, defined as HbA1c <7% (<53 mmol/mol) without experiencing hypoglycaemia after 26 weeks on BIAsp 30 therapy, were assessed.Results:The composite endpoint was defined for 44,010 (77%) patients from the total cohort of 57,478, and 28,696 of these were included in the statistical examination. The results of the analysis suggest that those with lower baseline HbA1c of ≤8% (≤64 mmol/mol), shorter duration of diabetes at baseline (<5 years) and no incidence of major hypoglycaemia at 13 weeks, or minor hypoglycaemia at 4 weeks, before the beginning of the trial were more likely to achieve treatment success.Conclusion:Lower baseline HbA1c, shorter duration of diabetes and no incidence of hypoglycaemia up to 13 weeks prior to initiation are predictors of achieving HbA1c <7% without hypoglycaemia with a BIAsp 30 regimen. These results suggest that it is easier to reach target without hypoglycaemia with BIAsp 30 when prescribed earlier. As this was an observational study, lack of control groups or randomisation, as well as varying clinical practices in study countries, potentially introduced bias.Trial registration:ClinicalTrials.gov identifier: NCT00659282.

UPDATE ON TREATMENT OF TYPE 2 DIABETES

80% patients with type 2 diabete are overweight and obesity. Hyperglycemia almost due to insulin-resistance; In overweight and obese insulin-resistant individuals, modest weight loss has been shown to reduce insulin resistance. Lifestyle changes that include moderate weight loss and regular physical activity (150-300min/week), with dietary strategies including reduced calories and reduced intake of dietary fat, can reduce the risk for developing the complication of diabetes. Therefore, MNT and exercise are the firt choice and metformin. People with diabetes should receive diabetes self-management education to have a good effective in therapy for type 2 diabetes. According to the guidelines in the World, individuals who have type 2 diabetes should receive individualized medical nutrition therapy (MNT) and exercise as needed to achieve treatment goals. In 2008 and update in 2011, 2012, new guideline of the IDC, the ADA and the EASD published an expert consensus statement on the approach to management of hyperglycemia in individuals with type 2 diabetes. Highlights of this approach are: intervention at the time of diagnosis with metformin (monotherapy with metformin as the initial pharmacologic therapy for most patients with type 2 diabetes) in combination with lifestyle changes (MNT and exercise), and continuing timely augmentation of therapy with additional agents (including early initiation of insulin therapy) as a means of achieving and maintaining recommended levels of glycemic control (Fasting plasma glucose or preprandial: 70-130mg/dl, 2 hours posprandial: &lt;180mg/dl and A1C &lt;7% for most patients/3 months). As A1C targets are not achieved, treatment intensification is based on the addition of another agent from a different class (sulfonylureas, meglitinides, thiazolidinediones, DPP-4 inhibitors, and GLP-1 receptor antagonist, insulin). Diabetes in adults is associated with a high risk of macrovascular disease, with CVD the primary cause of death among people with type 2 diabetes. For prevention of cardiovascular events among type 2 diabetes (MI, stroke, PAD..), beside treatment hyperglycemia, we have also to reduce hyperlipidemia and hypertension

Reduced endogenous insulin secretion in diabetic patients with low-titer positive antibodies against GAD

Aim: To investigate the clinical characteristics of diabetic patients with a low-titer positive for the anti-glutamic acid decarboxylase 65 antibody (GAD antibody). Methods: The subjects were 420 diabetic inpatients. The endogenous insulin secretion was estimated on the basis of the C-peptide immunoreactivity from a 24 h urine collection (uCPR). Clinical variables were compared between patients negative for the GAD antibody (GAD antibody titer < 1.5 U/mL), a low-titer positive GAD antibody (1.5 U/mL ≤ GAD antibody titer < 10 U/mL) and a high-titer positive GAD antibody (10 U/mL ≤ GAD antibody titer). Results: The low and high-titer positive GAD antibodies were found in 25 and 10 patients, respectively. The uCPR was significantly lower in both the patients with a low (37 ± 33 ug/24h) and high-titer (39 ± 27 ug/24h) positive GAD antibodies than in those negative for GAD antibodies (71 ± 52 ug/24h). The uCPR level was significantly lower in the low-titer positive GAD antibody group (29 ± 22 ug/24h) than in the negative group (67 ± 55 ug/24h) among the patients not taking insulin secretagogues. The difference disappeared in the subjects taking insulin secreagogues. In the stepwise multiple regression analysis, a low-titer positive GAD antibody was independently associated with the uCPR level. Conclusions: Endogenous insulin secretion is reduced in diabetic patients positive for GAD antibodies, even if the titer is low. Earlier initiation of insulin therapy might therefore protect the pancreatic β-cell function in diabetic patients with a low-titer positive GAD antibody.