Insulin Use In Patients Research Articles

Identifying and addressing barriers for insulin use in patients with type-2 diabetes mellitus

Background: DM type-2 is characterized by gradual decrease in insulin sensitivity within the peripheral tissues and liver (insulin resistance), followed by gradual decline in β-cell function and insulin secretion. Thus, patients with poor glycemic control require the utilization of insulin therapy to realize the target of yank Diabetes Association, recommending HbA1c to be but 7% (≥8% despite of optimal doses of anti-diabetic drugs). Aim: This study aimed to guage and addressing the barriers to be used of insulin in type-2 DM patients, where their glycemic control is poor, i.e., HbA1c is ≥8% despite of optimal doses of anti-diabetic drugs. Research Design & Method: We surveyed 200 patients with type-2 diabetes mellitus, i.e., cross-sectional quantitative study; patients showed poor glycemic control HbA1c≥8%, already treated with one or more oral agents, who recently prescribed insulin to regulate their metabolic status. Data were obtained by patient’s interview employing a validated questionnaire. The place of the study was in DM clinic in Farwaniyah Primary Health Care Center in Kuwait. Result: Patients with type-2 diabetes failing to initiate the prescribed insulin therapy have reported misconception regarding fear of hypoglycemia in 49% of the entire sample, pain from injections in 68% and self-blame about need for insulin i.e., sense of failure in 61% of total sample of study. Other factors were addressed like sensation by getting more severity of the disease, weight gain fear and other negative self-perceptions and attitudinal barriers were studied. Conclusion: Reducing the negative influence of psychological insulin resistance (PIR) on treatment outcomes should be a clinical priority. Approaching and understanding the multifaceted and sophisticated nature of PIR and discussing the etiology of each patient’s PIR is that the first important step. The incorporation of well-validated clinical measures assessing these barriers, also as further research should be conducted on the impact of interventions to beat such barriers. Clinicians should prescribe simple insulin regimen to decrease their patients’ fear from dependency of insulin and therefore the use of recent insulin analogs and insulin pen services, may greatly reduce PIR by mitigating the fear of life style changes and side effects, also as social stigma related to using insulin during a vial and syringe.

Seasonality of Insulin Use in German Outpatients With Diabetes: A Retrospective Analysis.

Seasonality in insulin sensitivity has been the focus of controversial literature in the past decades. The aim of this study was to analyze seasonality of insulin use in patients with diabetes who were followed in German general practices. This study included patients affected by type 1 (T1DM) or type 2 diabetes mellitus (T2DM) who received intensified conventional insulin therapy over a period of at least 12 months between 2013 and 2015. The main outcome was the median insulin dose per day (calculated daily insulin doses, CDDs) between June and August (summer) and between December and February (winter). The present study included 1197 T1DM patients and 3836 T2DM patients from 492 general practitioner or diabetologist practices. The mean age was 45.4 years (SD = 16.2 years) in the T1DM group and 65.2 years (SD = 14.1 years) in the T2DM group. The most frequent basal insulin therapy was insulin glargine (T1DM: 45.7%; T2DM: 41.1%), and the most frequent bolus insulin therapy was insulin lispro in the T1DM group (38.7%) and human insulin in the T2DM group (45.2%). The consumption of basal and bolus insulins did not significantly differ between summer and winter in T1DM individuals (basal therapy: 30.8 international units (IU)/day versus 31.2 IU/day; bolus therapy: 39.4 IU/day versus 37.8 IU/day). This consumption was also similar between the two seasons in the T2DM group (basal therapy: 31.0 IU/day versus 30.6 IU/day; bolus therapy: 44.3 IU/day versus 44.1 IU/day). There was no significant difference in the use of basal and bolus insulin therapies between summer and winter in German patients with T1DM or T2DM.

Real-World Glycemic Control from GLP-1RA Therapy with and Without Concurrent Insulin in Patients with Type 2 Diabetes.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are recommended as add-on therapy in patients with uncontrolled type 2 diabetes (T2D), with no specific guidance as to timing versus insulin. Furthermore, real-world data assessing GLP-1RA outcomes with or without concurrent insulin therapy are lacking. To identify glycemic response with GLP-1RAs by insulin use in patients with T2D at 1-year follow-up to inform decisions regarding GLP-1RA use with or without insulin. This uncontrolled retrospective cohort study included adults with T2D in the Quintiles Electronic Medical Records Database who were newly prescribed GLP-1RA therapy with exenatide once weekly or liraglutide once daily between February 1, 2012, and March 31, 2013 (index period). Primary outcomes were change in hemoglobin A1c (A1c) at 1 year and attainment of A1c < 7%, < 8%, and < 9%. Results were stratified by baseline insulin use, which was defined as no insulin use at baseline, insulin initiated with a GLP-1RA on index date, and insulin prescribed before starting GLP-1RA therapy. Secondary outcomes included 1-year weight, low-density lipoprotein cholesterol (LDL-C), and blood pressure outcomes for the study population. Adjusted mean (marginal) change in A1c at 1 year was estimated using multivariate linear regression, and multivariate logistic regression was used to estimate the likelihood of patients attaining A1c < 7% at follow-up, controlling for potential confounders. This study included 5,141 patients with a mean (SD) age of 57.0 (10.9) years, 53.5% of whom were females, and with a mean baseline A1c of 8.4% (1.6). Overall, 35.4% had no baseline insulin use, 42.9% were prescribed insulin before starting GLP-1RA therapy, and 21.7% were started on insulin with a GLP-1RA. The adjusted mean A1c reduction at 1 year was 0.75% (95% CI = -0.86 to -0.63) for patients initiating insulin on index date, 0.61% (95% CI = -0.70 to -0.51) for patients with no baseline insulin use, and 0.23% (95% CI = -0.33 to -0.13) for patients prescribed insulin before GLP-1RA therapy. Patients with no baseline insulin or who coinitiated insulin and a GLP-1RA were more likely to attain A1c < 7% at follow-up versus patients prescribed insulin before initiating GLP-1RA therapy (OR = 1.50, 95% CI = 1.08 to 2.09 and OR = 1.85, 95% CI = 1.30 to 2.62, respectively). At 1-year follow-up, significant improvements in weight, LDL-C, and blood pressures were also observed. GLP-1RA therapy was associated with significant improvements in glycemic control when used with or without insulin, as well as reductions in weight and LDL-C overall. However, greater A1c reductions and a higher likelihood of attaining A1c goal levels were observed when a GLP-1RA was initiated alone or with insulin than when a GLP-1RA was added to a regimen that included insulin. GLP-1RA therapy is an effective treatment option when used with or without insulin and may be considered in patients with uncontrolled glycemia. The study was funded by a collaborative research grant from AstraZeneca. Employees of AstraZeneca participated in most aspects of the study and in manuscript preparation. Nguyen and Hurd are employed by, and hold stock in, AstraZeneca. McAdam-Marx reports participation in the AMCP Diabetes Partnership and has stock ownership in GlaxoSmithKline. Study concept and design were contributed by Nguyen, McAdam-Marx, and Singhal, along with Unni and Schauerhamer. Singhal, Unni, Nguyen, and McAdam-Marx collected the data, with assistance from Schauerhamer and Hurd, and data interpretation was performed by Unni, Hurd, McAdam-Marx, Singhal, Nguyen, and Schauerhamer. The manuscript was written by Singhal, Schauerhamer, Unni, and McAdam-Marx, along with Nguyen and Hurd, and revised by McAdam-Marx, Singhal, Unni, and Nguyen, along with Schauerhamer and Hurd.

Prevalence of Psychological Insulin Resistance among Patients with Type 2 Diabetes at Kenyatta National Hospital, Kenya

Background: The psychological barriers to initiation and persistence with insulin therapy also referred to as Psychological Insulin resistance (PIR), interferes with use of insulin in patients with diabetes. However, ultimate use of insulin in majority of patients with type 2 diabetes is inevitable over time yet many of the patients still resist it because of PIR. The magnitude of PIR among type 2 diabetics is not known in many clinical practice settings, including Kenya. Patients and methods: This was a cross-sectional survey of PIR in subjects with type 2 diabetes at the Kenyatta National Hospital (KNH), which is a tertiary care and teaching hospital in Kenya, a developing country. Subjects were recruited from the Diabetes Outpatient Clinic where we obtained their socio-demographic and clinical data. We used Insulin Treatment Appraisal Scale (ITAS), which is a validated tool and a structured questionnaire, to collect information regarding psychological insulin resistance. Results: A total of 167 patients with type 2 diabetes were enrolled, where the females were 59.3%. The prevalence of Psychological Insulin Resistance was 82.6% and the mean ITAS score was 52.7. The gender, age, family history of diabetes, duration of diabetes of the patients and their duration of insulin therapy and ability to purchase medication had no significant influence on the positive and/or negative attitudes towards insulin therapy, (p>0.05). Patients who were using insulin had lower mean ITAS score 50.9, than the non-insulin users, ITAS score 59, which reflected lesser negative attitudes in the insulintreated group (p<0.05). The mean (SD) age was 55.5 (13.8) years and the mean (SD) duration of diabetes was 10.2 (8.7) years. Fifty four (32.3%) were on insulin-only treatment, 71 (42.5%) were on combination insulin and oral hypoglycemic agents and 42 (25.1%) were on oral hypoglycemic agents-only therapy. Conclusion: The prevalence of psychological insulin resistance (PIR) among the study patients was quite high at 82.6%. Patients who were already using insulin therapy showed less psychological resistance than the non-insulin user patients which implied a relative acceptance of insulin therapy in the patients who were already using it. Thus, PIR should be deliberately addressed as a unique condition in type 2 diabetes, recognizing from published work that there may be co-morbid depression in insulin users. Counseling patients with type 2 diabetes regarding insulin use should focus on, among many other issues, the perceptual domains of negative attitudes exhibited by a high proportion of them, because these negative attitudes towards insulin therapy can be mitigated. However, we recommend further studies to determine how PIR affects self-care and consequent metabolic control.

Insulinoterapia

Insulin is an essential component of therapy in patients with type 1 diabetes. In patients with type 2 diabetes, insulin therapy is a therapeutic option at any stage of the disease and, given the progressive nature, many patients require insulin in the advanced stages of the disease. Since the discovery of insulin, and especially from the knowledge of the physiological insulin secretion, advances in insulin therapy in general, and particularly in the development of insulin preparations have been spectacular. At present, we have a wide range of insulin preparations with different profiles of pharmacological activity that allow us to design insulin regimens tailored to the individual needs of each patient. This article reviews insulin preparations currently available, the main management guidelines and the indications for insulin use in patients with diabetes.

Needle-free nasal delivery of glucagon for treatment of diabetes-related severe hypoglycemia: toxicology of polypropylene resin used in delivery device

Context: The intranasal route is a promising route of administration for several emergency rescue drugs including naloxone and glucagon. Glucagon nasal powder (GNP) is a novel, needle-free delivery system for intranasal administration of glucagon for the treatment of severe hypoglycemia, an infrequent but serious complication of insulin use in patients with diabetes. The GNP delivery device is a compact, highly portable, single-use nasal powder dosing device constructed of polypropylene that allows for simple, single-step administration.Objective: To evaluate the toxicological profile of the polypropylene resin used in the actuator part of the delivery device that will contact skin and nasal mucosal membranes of the patient, we performed an in vitro cytotoxicity study, a skin sensitization study and an irritation (intracutaneous reactivity) study in animal models.Methods: Extracts of the actuator of the GNP device were generated from HAM F12 medium with 10% fetal bovine serum, 0.9% sodium chloride (NaCl) or sesame oil. The in vitro cytotoxicity test was performed in cultured L929 mouse fibroblasts. Skin sensitization analysis was performed in 10 guinea pigs according to the Magnusson–Kligman method, using a maximization method with Freund's Complete Adjuvant. Irritation following intracutaneous/intradermal treatment with device extracts (NaCl and sesame oil extractants) was assessed in three New Zealand White rabbits.Results: In vitro cytotoxicity test: Both undiluted and diluted extract showed no toxicity (i.e. no abnormal morphology, cell death or cell lysis) toward L929 fibroblasts (cytotoxicity grade 0). Sensitization test in guinea pigs: Challenge with device extracts did not evoke positive responses in test animals previously induced with device extracts. The net response value represented an incidence rate of 0% and a net dermal irritation score value of 0.00. Irritation (intracutaneous/intradermal) test in New Zealand White rabbits: Device extracts and corresponding vehicle controls caused similar irritation reactions. The difference between the mean scores for the device extracts and the corresponding vehicle controls was less than 1.0.Conclusions: Extracts of the polypropylene resin of the GNP delivery device are not cytotoxic, do not result in dermal sensitization and do not cause irritation when applied topically or intracutaneously. Given the infrequent use and very short duration of exposure to the nasal mucosa during administration of GNP, the polypropylene resin of the GNP device actuator will likely not cause adverse dermal sensitization effects or irritation effects in humans and can, therefore, be considered for use as a delivery device in clinical trials assessing the efficacy and safety of GNP for the treatment of insulin-using patients experiencing episodes of severe hypoglycemia.

Psychological insulin resistance in patients with type 2 diabetes mellitus

Aim Our study was conducted to review factors responsible for psychological insulin resistance among patients with type 2 diabetes mellitus. Patients and methods In our study on 100 patients with type 2 diabetes mellitus enrolled from an outpatient clinic of diabetes, all patients were noncompliant to diet and exercise, with high HbA1c, and all planned to be converted to insulin therapy. Results The results showed that a large number of factors account for psychological insulin resistance in patients; the main categories were emotional, cognitive, social, cultural, and interaction with health providers. Conclusion We concluded that there is a significant need of evidence-based interventions that help remove psychological barriers about insulin use in patients.

Predictors of Early Insulin Use in Patients with Type 2 Diabetes: A Cross-Sectional Study

To determine the factors associated with early use of insulin following a diagnosis of type 2 diabetes.

Use of Insulin and Insulin Analogs and Risk of Cancer — Systematic Review and Meta-Analysis of Observational Studies

Background:An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified.Objective: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes.Data Sources: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library.Study Eligibility Criteria (PICOS): Population: diabetes patients. Exposure: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs. Outcome: Any incident cancer. Study Design: Cohort and case-control studies.Results: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer.Limitations: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders.Conclusions: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.

Insulin Use in Long Term Care Settings for Patients With Type 2 Diabetes Mellitus: A Systematic Review of the Literature

To summarize currently available data about insulin therapy in patients with diabetes mellitus (DM), focusing on patients with type 2 DM (T2DM), in long term care (LTC) settings. Ovid Medline, EMBASE, Cochrane Library databases, and United Kingdom National Health Service (NHS) Economic Evaluation Database, last accessed on November 12,2012. We included studies that reported insulin use in patients with T2DM, and studies with combined samples of patients with type 1 DM or T2DM, that were conducted in LTC settings. Excluded were review articles and studies published before2000. We identified 11 articles that metall inclusion and exclusion criteria. Insulin use in patients with DM in LTC settings varied widely, from 2.7% to 58.0%. It is difficult to draw conclusions from these proportions, as many studies did not define whether their populations were exclusively patients with T2DM. Despite recommendations against its use by the American Diabetes Association, the American Geriatrics Society, and the American Medical Directors Association, treatment with sliding-scale insulin (insulin injections adjusted to current blood glucose levels) was prevalent in the LTC setting. Although the recommended target hemoglobin A1c (A1C) for this patient population varies from ≤6.5% to ≤8.0%, higher A1C values (8.0%-8.9%) were associated with better patient outcomes in a study examining insulin treatment in community-dwelling elderly patients enrolled in an outpatient LTC setting. Insulin pen-devices seemed associated with a high incidence of needle-stick injuries in workers in LTC settings but, compared with insulin vials, showed cost advantages for use in very short-term (≤30 days) patients with DM in LTC settings. Paucity of available data; only published studies for which full-text articles could be retrieved and which were identified by our search strategy were included; insufficient detail about patient samples were available in many included studies; and potential biases across studies might be introduced by funding sources or study designs. Available data about insulin therapy in patients with DM in LTC settings are very scarce and great treatment variability of this patient population seems to prevail in the current clinical practice. Additional, randomized, prospective clinical trials are needed to expand our knowledge and allow clinicians to make informed treatment decisions for patients with DM in LTC settings.

“Position Paper” Timely Insulinisation in Type 2 Diabetes Patients

AbstractThe objective of this position paper is to review the current medical evidence andguidelines regarding the treatment of type 2 diabetes (T2DM) and to issue medicalrecommendations strengthening the timely use of insulin in patients with T2DMuncontrolled on noninsulin therapy. When noninsulin therapy fails to achieve or tomaintain HbA1c targets, insulin therapy is required. Timely insulin therapy couldprovide proper metabolic control that might prevent complications, lead toimprovement of life expectancy and quality of life.

Diabetes, insulin use and Helicobacter pylori eradication: a retrospective cohort study

BackgroundDiabetic patients may have a higher risk of gastric cancer. However, whether they have a higher incidence of Helicobacter pylori (HP) eradication is not known. Furthermore, whether insulin use in patients with type 2 diabetes may be associated with a higher incidence of HP eradication has not been investigated.MethodsThis is a retrospective cohort study. The reimbursement databases from 1996 to 2005 of 1 million insurants of the National Health Insurance in Taiwan were retrieved. After excluding those aged <25 years, cases of gastric cancer, cases receiving HP eradication before 2005, patients with type 1 diabetes mellitus and those with unknown living region, the reimbursement data of a total of 601,441 insurants were analyzed. Diabetes status and insulin use in patients with type 2 diabetes before 2005 were the main exposures of interest and the first event of HP eradication in 2005 was the main outcome evaluated. HP eradication was defined as a combination use of proton pump inhibitor or H2 receptor blockers, plus clarithromycin or metronidazole, plus amoxicillin or tetracycline, with or without bismuth, in the same prescription for 7-14 days. The association between type 2 diabetes/insulin use and HP eradication was evaluated by logistic regression, considering the confounding effect of diabetes duration, comorbidities, medications and panendoscopic examination.ResultsIn 2005, there were 10,051 incident cases receiving HP eradication. HP eradication was significantly increased with age, male sex, diabetes status, insulin use, use of calcium channel blocker, panendoscopic examination, hypertension, dyslipidemia, chronic obstructive pulmonary disease, stroke, nephropathy, ischemic heart disease and peripheral arterial disease. Significant differences were also seen for occupation and living region. Medications including statin, fibrate, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and oral anti-diabetic agents were not associated with HP eradication. The adjusted odds ratios for diabetes, insulin use and use of calcium channel blocker was 1.133 (1.074, 1.195), 1.414 (1.228, 1.629) and 1.147 (1.074, 1.225), respectively.ConclusionsType 2 diabetes and insulin use in the diabetic patients are significantly associated with a higher incidence of HP eradication. Additionally, use of calcium channel blocker also shows a significant association with HP eradication.

Endothelial insulin receptor expression in human atherosclerotic plaques: Linking micro- and macrovascular disease in diabetes?

ObjectiveExogenous insulin use in patients with type 2 diabetes (DM2) has been associated with an increased risk of cardiovascular events. Through which mechanisms insulin may increase atherosclerotic plaque vulnerability is currently unclear. Because insulin has been suggested to promote angiogenesis in diabetic retinopathy and tumors, we hypothesized that insulin enhances intra-plaque angiogenesis. MethodsAn in vitro model of pathological angiogenesis was used to assess the potential of insulin to enhance capillary-like tube formation of human microvascular endothelial cells (hMVEC) into a three dimensional fibrin matrix. In addition, insulin receptor expression within atherosclerotic plaques was visualized in carotid endarterectomy specimens of 20 patients with carotid artery stenosis, using immunohistochemical techniques. Furthermore, microvessel density within atherosclerotic plaques was compared between 68 DM2 patients who received insulin therapy and 97 DM2 patients who had been treated with oral glucose lowering agents only. ResultsInsulin, at a concentration of 10−8M, increased capillary-like tube formation of hMVEC 1.7-fold (p<0.01). Within human atherosclerotic plaques, we observed a specific distribution pattern for the insulin receptor: insulin receptor expression was consistently higher on the endothelial lining of small nascent microvessels compared to more mature microvessels. There was a trend towards an increased microvessel density by 20% in atherosclerotic plaques derived from patients using insulin compared to plaques derived from patients using oral glucose lowering agents only (p=0.05). ConclusionExogenous insulin use in DM2 patients may contribute to increased plaque vulnerability by stimulating local angiogenesis within atherosclerotic plaques.

Psychological insulin resistance: a critical review of the literature

AbstractOur objective was to conduct a critical review of the factors that account for psychological insulin resistance (PIR) and of the available strategies to reduce it.Medline, PubMed, Cochrane reviews, PsycInfo, ProQuest, Science Direct, and EBSCO databases were searched and 60 studies were included in the final review. Topics reviewed included: research methods, instruments to assess PIR, PIR in patients and in the medical care team, and proposed strategies for overcoming it.The results showed that a large number of factors account for PIR in patients. The main categories are emotional, cognitive, social/cultural, and interaction with health providers. Physicians mainly delay insulin because they lack knowledge on guidelines or pancreas physiology, they fear inducing hypoglycaemia in elderly or impaired patients, and/or they lack time or personnel resources to teach initiation. Strategies proposed to reduce PIR are educational and psychological (exposure, desensitisation, relaxation and counselling).We concluded that there is a great need of evidence‐based interventions that help remove psychological barriers about insulin use in patients, as well as in health care providers. Copyright © 2011 John Wiley &amp; Sons.

Reconsideration of Severe Hypoglycemic Events in the Treat-to-Target Trial

This article reevaluates the hypoglycemic episodes reported as severe in the Treat-to-Target Trial comparing insulin glargine and NPH insulin use in patients with inadequately controlled type 2 diabetes. Case report forms from the Treat-to-Target Trial were reviewed to identify additional severe hypoglycemic events and to further characterize those events already identified. Severe hypoglycemia was defined as symptoms consistent with hypoglycemia requiring assistance of another person and associated with either glucose levels < or =56 mg/dL or prompt recovery after oral carbohydrate intake, intravenous glucose administration, or glucagon injection. This analysis confirmed that severe hypoglycemia was similarly uncommon with both insulins (insulin glargine [n = 367], nine patients, 14 events; NPH insulin [n = 389], nine patients, 13 events); all hypoglycemic events for glargine and nine for NPH were treated effectively at home. All severe hypoglycemic episodes were associated with sulfonylurea use. A review of case report forms demonstrated inconsistencies in identification of severe hypoglycemia (seven of 14 severe events for glargine and three of 13 severe events for NPH were coded as moderate). The rate of severe hypoglycemia in this trial was low. Difficulties in gathering and interpreting hypoglycemia data highlight the need for more objective methods.

Insulin therapy in type 2 diabetes: what is the evidence?

To systematically review the literature regarding insulin use in patients with type 2 diabetes mellitus A Medline and Embase search was performed to identify randomized controlled trials (RCT) published in English between 1 January 2000 and 1 April 2008, involving insulin therapy in adults with type 2 diabetes mellitus. The RCTs must comprise at least glycaemic control (glycosylated haemoglobin (HbA1c), postprandial plasma glucose and /or fasting blood glucose (FBG)) and hypoglycaemic events as outcome measurements. The Pubmed search resulted in 943 hits; the Embase search gave 692 hits. A total of 116 RCTs were selected by title or abstract. Eventually 78 trials met the inclusion criteria. The studies were very diverse and of different quality. They comprised all possible insulin regimens with and without combination with oral medication. Continuing metformin and/or sulphonylurea after start of therapy with basal long-acting insulin results in better glycaemic control with less insulin requirements, less weight gain and less hypoglycaemic events. Long-acting insulin analogues in combination with oral medication are associated with similar glycaemic control but fewer hypoglycaemic episodes compared with NPH insulin. Most of the trials demonstrated better glycaemic control with premix insulin therapy than with a long-acting insulin once daily, but premix insulin causes more hypoglycaemic episodes. Analogue premix provides similar HbA1c, but lower postprandial glucose levels compared with human premix, without increase in hypoglycaemic events or weight gain. Drawing conclusions from the limited number of studies concerning basal-bolus regimen seems not possible. Some studies showed that rapid-acting insulin analogues frequently result in a better HbA1c or postprandial glucose without increase of hypoglycaemia than regular human insulin. A once-daily basal insulin regimen added to oral medication is an ideal starting point. All next steps, from one to two or even more injections per day should be taken very carefully and in thorough deliberation with the patient, who has to comply with such a regimen for many years.

Does Rapid Transition to Insulin Therapy in Subjects with Newly Diagnosed Type 2 Diabetes Mellitus Benefit Glycaemic Control and Diabetes-related Complications? A German Population-based Study

The aim of this study was to assess whether earlier transition to insulin in subjects with newly diagnosed type 2 diabetes improves glycaemic control and reduces diabetes-related complications. Subjects with newly diagnosed type 2 diabetes, and 2 or more recorded glycosylated haemoglobin (HbA1c) values, were identified from the Mediplus Germany database between June 1993 and May 2001. Subjects were stratified by treatment group: diet and exercise, sulfonylurea drugs, antihyperglycaemic drugs, insulin, or insulin plus sulfonylurea or antihyperglycaemic drugs. Treatment modifications were tracked over time and a rapid transition to insulin recorded if insulin was the initial therapy administered or the immediate treatment after diet and exercise. The area under the curve (AUC) for HbA1c was calculated and a linear regression model used to explain AUC as a function of rapid transitioning to insulin. A Cox proportional hazard model assessed the relationship between the time to first complication and AUC, rapid transition to insulin, and the number of treatment modifications. Of the 3136 subjects who met the study entry criteria, just 151 (4.8%) were initiated on insulin; after 5 years only 811 (25.9%) subjects had received insulin therapy. In the regression model explaining AUC, rapid transition to insulin significantly improved glycaemic control (-0.20, p=0.03). The Cox proportional hazard model demonstrated that the time to first complication was negatively related to AUC (-0.05, p<0.01) and the rapid use of insulin (-0.27, p<0.01), and positively related to the number of treatment modifications (0.07, p<0.01). Using actual real world clinical practice data, the present study found that the immediate use of insulin in patients with type 2 diabetes improved blood glucose control as measured by the AUC for HbA1c readings. This, in turn, reduced the risk of diabetes-related complications. In contrast, we observed that a stepwise transition treatment pattern (switching from diet and exercise to sulfonylureas and then perhaps to antihyperglycaemic agents and finally insulin) increased the risk of diabetes-related complications. Greater effort is required to remove some of the barriers currently preventing earlier initiation of insulin therapy in patients with type 2 diabetes.

Determinants of daily insulin use in Type 1 diabetes

Objective Insulin need for a given degree of glucose control varies markedly among individuals. We examined which factors determine daily insulin use in patients with Type 1 diabetes. Methods A cross-sectional study was performed in 416 patients. Clinical parameters, medication use, physical activity, smoking, alcohol consumption, and laboratory parameters were determined. Results Body mass index and waist circumference were positively related to daily insulin use (2.3 U/kg/m 2, 95% CI=1.9–2.7 and 0.8 U/cm, 95% CI=0.6–0.9, adjusted for age and sex). Age, female sex, and duration of diabetes were inversely related to daily insulin dose. There was an increase of 3.6 U of insulin per mmol/l triglycerides (95% CI=1.04–6.2) and a decrease of 5.9 U of insulin per mmol/l high-density lipoprotein cholesterol (95% CI=−10.0 to −1.8), adjusted for age, sex, and weight. For blood pressure-lowering drugs, the strongest relation was found for thiazide diuretics (difference of 7.1 U insulin/day, 95% CI=0.2–14.2, adjusted for age, sex, and weight). The use of an insulin pump and physical activity were related to lower daily insulin need: −8.7 U/day (95% CI=−11.8 to −5.5) and −1.7 U/day per activity score unit (95% CI=−3.2 to −0.2), respectively, adjusted for age, sex, and weight. Smoking was related to an increased need of 5.3 U/day (95% CI=1.5–9.0), adjusted for age, sex, and weight. Conclusions Our results show that components of the metabolic syndrome are positively related to daily insulin use. Also, decreased physical activity, smoking, and the use of blood pressure-lowering drugs, which influence insulin sensitivity, are associated with an increased insulin need. These findings suggest that the presence of insulin resistance in Type 1 diabetes or “double diabetes” plays a key role in determining daily insulin need.

The role of basal insulin therapy in patients with type 2 diabetes mellitus

Background: The natural course of type 2 diabetes mellitus (DM) is characterized by insulin resistance followed by a progressive decline in β-cell function, which results in relative insulin deficiency. At diagnosis, a patient with tvpe 2 DM has only 50%, of β-cell function remaining. Given this inevitable decline in β-cell function and insulin secretion, most patients with type 2 DM will require insulin therapy at some point. Objective: The objective of this article was to provide a brief overview of physiologic insulin secretion and to discuss the role of basal insulin therapy in patients with type 2 DM. Methods: Materials for this article were identified through searches (2000–2005) of MEDLINE and Google, as well as from the author's personal files. Search terms included basal insulin, titration, hypoglycemia, glycemic control, and basal-bolus therapy. Results: The cfficacy of insulin either as nmonotherapy or in combination with oral agents in type 2 DM is well established. Insulin therapy has also been show to improve insulin sensitivity and, in some cases, reverse insulin resistance, possibly by elimination of glucose toxicity. In recent years, the availability of insulin formulations with more favorable pharmacokinetic profiles has reduced concerns about hvpoglycemia and weight gain, facilitating the use of insulin in patients with type 2 DM. For insulin-naive patients who are inadequately controlled on oral antidiabetic drugs, the addition of a single basal insulin dose at bedtime has been found to reduce glycosylated hemoglobin (A1C levels,with a low risk of nocturnal hypoglycemia. Basal insulins. (ie, glargine, detemir) have also been shown to induce less weight gain a significant concern for both patients and providers. The use of long-acting basal insulins may also reduce intrapatient variability in fasting blood glucose values. Moreover, the long-acting basal insulins such as glargine and detemir can be administered QD, which may enhance the potential for patient compliance. Aggressive titration of insulin doses based on a target fasting plasma glucose level of 100 to 120 mg/dL is essential to achieving target A1C levels (<7.0%,). As β-cell function declines, patients may require switch to basal-bolus insulin therapy. Although the long- and intermediate-acting insulin formulations are comparable with regard to efficacy as the basal component in basal-bolus therapy, the long-acting insulins have been associated with lower rates of nocturnal hypoglycemia, which can have a positive effect on glycemic control during the daytime. Conclusion: Basal insulins, both intermediate- and long-acting formulations, are playing an increasingly important role in the treatment of type 2 DM.

Abstract #834: Effect of Pramlintide on Hemoglobin A1c, Body Weight, and Insulin Use in Patients with Type 1 Diabetes Failing to Achieve Glycemic Targets with Insulin Therapy

Abstract #834: Effect of Pramlintide on Hemoglobin A1c, Body Weight, and Insulin Use in Patients with Type 1 Diabetes Failing to Achieve Glycemic Targets with Insulin Therapy