Insulin therapy for diabetes mellitus: treatment regimens and associated costs.

AIMS: To describe insulin therapy in patients with diabetes, to determine treatment costs and to compare costs among treatment regimens. METHODS: This observational study was performed by 734 French pharmacists. Adult patients filling an insulin prescription were invited to participate. Participants provided information on their diabetes history and management. Levels of intensification of insulin therapy were determined by the number of injections in type 1 diabetes mellitus (T1DM) patients, and by the different schemes used in type 2 (T2DM) patients, such as basal/intermediate-acting insulin only, and regimens using both basal and rapid-acting insulin. Costs were evaluated according to official medication costs, nurse visits and glucose monitoring kits. RESULTS: A total of 361 patients with T1DM and 1902 with T2DM were enrolled in the survey. Patients with T1DM more frequently took 1-2 injections per day (46.3% of patients) and used single-dose basal insulin together with ≥1 dose of rapid insulin (43.8%). Patients with T2DM used multiple treatment regimens, with 58 different combinations documented. Most took basal/intermediate insulin only (42.5%) or combinations of basal/intermediate and rapid insulins (52.7%). Mean cost of insulin therapy was €27.4/week for T1DM and €45.4/week for T2DM. In T1DM, insulin was the biggest cost component and increased with the number of injections/day. In T2DM, nurse visits were the most important cost contributors irrespective of treatment regimen. Overall, the cost of insulin therapy increased with the complexity of the insulin schemes. CONCLUSION: Considerable heterogeneity is found in insulin treatment regimens used in everyday diabetes care. Payers should consider the full costs associated with the use of insulin rather than the cost of insulin alone. Treatment algorithms to harmonize insulin therapy should help to improve care, while encouraging patients to self-inject insulin should help to reduce costs.

Improving diabetes management with electronic medical records.

Most primary-care physicians have adopted electronic medical records (EMRs) for the management of patients in ambulatory care. Observational trials suggest that the use of EMRs improves the achievement of the recommended standards of diabetes care and intermediate outcomes. A French group of general practitioners has shown, in a randomized controlled trial of diabetes care, the beneficial effects of a follow-up module integrated into an EMR. Electronic reminders, eHealth technology and e-mail messaging to patients integrated into the EMR have also been reported to have a beneficial effect on diabetes care. Some recommendations have been devised for the meaningful use of EMRs to improve the process and, possibly, intermediate outcomes of diabetes care as well. Another potential benefit to consider is the extraction and aggregation of data to create diabetes registers. Large regional and national diabetes registers have been set up in the US and Europe for various purposes, including patient recall, description of care patterns and outcomes, improvement of practices, drug safety, observational research and retrospective trials. In France, the government initiative towards an Internet-based personal health record (PHR) provides an appropriate framework for implementing and sharing the information needed to improve diabetes care, such as electronic summaries of health information, personalized health plans (PHPs), and standardized and structured hospital-discharge forms. All of these materials can be generated from EMRs. The widespread and optimalized use of EMRs for diabetes care with links to the national diabetes register and the capacity to supply PHRs are major considerations. Achieving these goals requires a common initiative comprising primary care and diabetes scientific societies in cooperation with diabetes patients'associations.

Feasibility of screening for silent myocardial ischaemia according to the ALFEDIAM-SFC 2004 Guidelines in a population of diabetic patients.

BACKGROUND: Screening tests have to meet a number of criteria, including feasibility. The aim of this study was to estimate the proportion of the French diabetic population that is eligible for screening for silent myocardial ischaemia (SMI), and to evaluate the feasibility of such screening in the Franche-Comté region. METHODS: Data were taken from the Echantillon National Témoin Représentatif de la Population Diabétique (ENTRED, a Representative National Sample of the Diabetic Population 2001 study), which was based on questionnaires filled out by 3646 diabetic patients. All screening tests carried out in the region of Franche-Comté in eastern France in 2003 were recorded (n=19,216). RESULTS: The guidelines issued by the ALFEDIAM-SFC in 2004 were applied to the ENTRED population and identified 645 diabetic patients (17%) as eligible for SMI screening. When applied to the region of Franche-Comté, the recommendations would have required screening 7480 diabetic patients over a period of 3years, involving 1246 exercise stress tests and 1246 myocardial perfusion or stress echocardiography studies annually. However, more than 14,653 exercise stress, 4248 myocardial perfusion and 315 stress echocardiography tests were carried out in the region in 2003 among diabetic and non-diabetic patients, thus largely covering the screening requirements. On the other hand, ENTRED 2001 data also showed that 60% of patients who reported existing coronary disease would not have met screening criteria. CONCLUSION: The number of examinations carried out in the region of Franche-Comté greatly exceeded the number of patients required for screening. However, practical feasibility is not the only criterion needed to guarantee the quality of a large-scale screening programme. Our results raise the question of the relevance of the current screening selection criteria.

Sexual activity in diabetic patients treated by continuous subcutaneous insulin infusion therapy.

BACKGROUND AND AIMS: As concerns over interference with sexual activity may be an obstacle to initiating pump therapy in diabetic patients, the aim of the study was to assess the impact of continuous subcutaneous insulin infusion (CSII) therapy on sexual activity. PATIENTS AND METHODS: Patients filled out a questionnaire on their demographic data, diabetes history, pump-treatment history, metabolic control, inconvenience/convenience of the pump and catheter, and information on sexual activity. RESULTS: A total of 271 diabetic patients (aged 44+/-17 years, 51% women, 22% single), treated with CSII for 4.2+/-5.9 years and with a diabetes duration of 19+/-11 years, filled out the questionnaire. Their HbA(1c) was 7.7+/-1.1%, with 2.4+/-2.1 mild hypoglycaemic episodes over the past week, and their frequency of sexual activity was: never 29.9%; <1/month 12.3%; >1/month and <1/week 18.2%; and >1/week 39.6%. Age and cohabitation were independently correlated with frequency of sexual activity (P<0.0001 and P<0.0003, respectively), but not diabetes duration or complications. To the question "Does the pump have an influence on your sexual activity?", The answer was "no" in 90% and "yes" in 10%. However, intercourse frequency was significantly decreased in the latter (P=0.04). On multivariate analyses, this negative influence of CSII was correlated with HbA(1c) (P<0.05), discomfort with the pump (P<0.05) and the number of mild hypoglycaemic episodes (P<0.01). CONCLUSION: Frequency of sexual activity appears to be unaffected by pump therapy or diabetes, but is decreased by the expected characteristics-namely, age and being single. Also, only 10% of patients believe that CSII is an obstacle during sexual activity and, in particular, because of the catheter.

Real-life application and validation of flexible intensive insulin-therapy algorithms in type 1 diabetes patients.

AIMS: Flexible intensive insulin therapy (FIT) has become the reference standard in type 1 diabetes. Besides carbohydrate counting (CHO), it requires the use of algorithms to adjust prandial insulin doses to the number of CHO portions. As recourse to standard algorithms is usual when initiating FIT, the use of personalized algorithms would also allow more precise adjustments to be made. The aim of the present study was to validate personalized prandial algorithms for FIT as proposed by Howorka et al. in 1990. METHODS: We conducted a 4-month observational study of 35 patients with type 1 diabetes, treated with FIT for at least 6 months, who were already using Howorka's prandial algorithms (meal-related and correctional insulin doses for blood glucose increases induced by CHO). These patients were asked to use a personal digital assistant (PDA) phone with an electronic diary (instead of a paper one) to take advantage of the computerized data-collection system to assess the quality of postprandial metabolic control. RESULTS: Whatever the number of CHO portions, mean postprandial blood glucose values remained close to the target of 7.8mmol/L, and the compensatory algorithm allowed precise correction of preprandial hyperglycaemia. In fact, the algorithms for meal-related and correctional insulin doses at the end of the study did not differ significantly from those initially calculated, but they generally differed from one patient to another. CONCLUSION: In type 1 diabetic patients treated with FIT, the use of individualized parameters permits fast and accurate adjustment of mealtime insulin doses, leading to good control of the postprandial state.

Prevalence of macrovascular complications and cardiovascular risk factors in people treated for diabetes and living in France: the ENTRED study 2001.

AIM: The aim of this study is to estimate the prevalence of macrovascular complications and cardiovascular risk factors among people with diabetes living in France and to compare these prevalences with other national estimates. METHODS: We randomly sampled 10,000 people who received one or more reimbursements for insulin or oral hypoglycaemic treatment from the major national medical insurance system during the period October-December 2001; 3646 of the 10,000 people completed a questionnaire; for a subgroup of 1718 people, their care providers completed a medical questionnaire. RESULTS: The prevalence of diagnosed macrovascular complications was of 17% according to patients (angina or myocardial infarction, 15%; coronary revascularization, 9%) and of 20% overall, according to physicians (angina or myocardial infarction, 16%; coronary revascularization, 6%; stroke, 5%). Macrovascular complications were more frequent in people with type 2 than type 1 diabetes, reflecting an age effect. The prevalences of cardiovascular risk factors in type 1 and type 2 diabetes were: current smoking, 35 and 14%; overweight, 28 and 42%; obesity, 9 and 36%; blood pressure superior to 130/80 mmHg, 29 and 59%; LDL cholesterol superior or equal to 3.4 mmol/l, 18 and 26%, respectively. CONCLUSIONS: Compared with other European countries, elevated blood pressure is more frequent in people with diabetes living in France; compared with US estimates, the prevalence of macrovascular complications is lower, glucose control better and blood pressure control poorer in France. These data, observed in a country with widespread access to care and at low cost to the patient, nevertheless demonstrate an urgent need for improving the cardiovascular risk profile of people with type 1 and type 2 diabetes, both with and without macrovascular complications.

French medical practice in type 2 diabetes: the need for better control of cardiovascular risk factors.

AIMS: In type 2 diabetes (T2D), to describe treatments to prevent cardiovascular disease, to compare current practice to French guidelines, and to identify factors associated with recommended treatments. METHODS: In the Echantillon National Témoin Représentatif des Personnes Diabétiques (ENTRED) study, 10,000 adults treated for diabetes (any type) were randomly selected from the French National Health Insurance System database. Deliveries during the last quarter of 2001 of treatments to prevent cardiovascular disease were extracted. Questionnaires were mailed to these people and their care providers. Final populations included 3324 people with T2D and their 1553 care providers. RESULTS: Overall, 18% reported coronary heart disease (CHD) and 44% others were classified as having a high cardiovascular risk; 68% received one or more antihypertensive treatment: ACE inhibitor/angiotensin receptor blocker (ARB), 44%; diuretic, 35%; calcium channel blocker, 25%; beta-blocker, 24%. Among those receiving antihypertensive treatment, 59% had blood pressure greater than 130/80mmHg. Overall, 42% received a hypolipidaemic treatment: statin, 25%; fibrate, 18%. About half the people with a high cardiovascular risk had LDL cholesterol greater than 1g/L, but only 32% were given a statin. Among people with an abnormal albumin/creatinine ratio (11%), 59% received an ACE inhibitor/ARB. Among those with CHD, 35% received the two treatments recommended in 1999 (beta-blockers and antiplatelet agents); in multivariate analyses, this two-treatment delivery was positively associated with male gender, self-reported hypertension and consulting a cardiologist. CONCLUSION: Cardiovascular risk profiles reported by providers in T2D people are high. Despite recent progress, there is a need for major improvement in practices intended to prevent cardiovascular disease in these people, especially in those at greatest CHD risk.

Improving glycaemic control of patients with Type 2 diabetes in a primary care setting: a French application of the Staged Diabetes Management programme.

AIMS: To assess the impact of a French adaptation of the Staged Diabetes Management (SDM) programme on glycaemic control of people with Type 2 diabetes in primary care. Secondary endpoints were blood pressure, blood lipids, healthcare costs and quality of life. METHODS: Prospective, randomized controlled study, of 1 years' duration. General practitioners (GPs) were recruited in four separate districts of a French region. They enrolled consecutive patients with Type 2 diabetes. GPs in the intervention group were educated in the SDM programme. GPs in the control group were asked to provide usual care. Healthcare costs were collected by medical departments of the Health Insurance systems. Quality of life was assessed with the Duke Health Profile. RESULTS: Three hundred and forty patients enrolled by 57 GPs completed the study, 192 in the intervention group and 148 in the control group. Patients in the intervention group were managed more adequately in accordance with the guidelines (P < 0.05 for nine out of 10 items). HbA(1c) decreased by 0.31% in the intervention group and increased by 0.56% in the control group, resulting in a difference of 0.87% by the end of the study (P = 0.001). Blood pressure and blood lipids did not differ between groups. Occurrence of major complications was low and identical in both groups. Incremental costs during the study in the intervention group were 35 euros per patient per month, and this was not significantly different in comparison with the control group. Quality of life was not affected by the intervention. CONCLUSIONS: Educating GPs in the French adaptation of the SDM programme improves glycaemic control in a primary care setting, without significantly increasing healthcare costs.

Sulfonylureas and cardiovascular effects: from experimental data to clinical use. Available data in humans and clinical applications.

OBJECTIVES: 33 years after the UGDP study, the question of deleterious effects of the sulfoylurea (SU) is still raised. We have made a systematic review of the literature from experimental studies to clinical and epidemiological studies. RESULTS: The main molecule studied is glibenclamide (GB). In vitro and in animal studies, GB is both deleterious for ischemic preconditionning (IPC) and protective for arrhythmia during acute ischemia. Glimepiride (GM) and gliclazide (GCZ) do not seem to have effect on IPC. These effects have been few studied in diabetic animals. In human, according to the investigations used, the GB seems nil or suppressing for IPC, it seems elsewhere decreases ventricular arrhythmias during periods of acute ischemia. It is possible that these two actions account for the non-appearance of concordant deleterious effects between short and long-term studies. With regards to other drugs, only the GM has been specifically studied in human and appears to be nil on IPC. The only prospective clinical study available, although not having for objective to answer to this question, is the UKPDS study. This trial demonstrates the absence of deleterious cardiac effects of GB compared to chlorpropamide and particularly compared to insulin. CONCLUSION: In conclusion, in experimental studies the cardiac effects of SU differ: both deleterious and protective for GB, nil for GM and GCZ on IPC. In all cases the clinical consequences seems to be nil.

Effects of clinical audit on the quality of care in patients with type 2 diabetes: results of the DIABEST pilot study.

OBJECTIVE: To improve the quality of diabetes care in general practice by the use of audit. MATERIAL AND METHODS: A prospective multicenter pilot study. Thirty-five groups of ten general practitioners (GPs) have been set up throughout France on a voluntary basis. These groups were led by a steering committee that includes a diabetologist and a GP. Each group established a consensus on healthcare standards and carried out 2 data collections over a 12-month period, with adoption of corrective measures between these 2 collections. RESULTS: 309 (90.4%) of the 342 practitioners completed the first data collection, assessing the management of 3,125 patients over a year. Less than half the groups have reached the 80% reference threshold for quality of care with regard to foot examination, microalbuminuria, ECG, fundoscopy and assessment of diet. The audit also found no intervention within one year in case of poor glucose control for 47% of patients, unsatisfactory quality of HbA(1c) measurement and insufficient resources for diet and education. 226 (66.1%) practitioners completed the second data collection assessing the management of 2,248 patients. Comparison between the two phases of the audit showed significant improvements for all the indicators of the process of care (p<0.001). Quality of HbA(1c) measurement and diet assessment by GPs progressed (p<0.01). Outcomes of care also improved with respect to the proportion of patients with HbA(1c)<=8% (p=0.007), fasting glycaemia<1.40 g/l (p=0.05) and SBP<140 mmHg (p=0.02). CONCLUSIONS: This pilot study confirms the feasibility of using clinical audit at the national level. It seems to be an effective measure to improve the management of patients with type 2 diabetes in primary care. It is intended that the large-scale DIABEST study will address this issue.

Management of drugs affecting blood glucose in diabetic patients with renal failure.

Prevention of the onset or worsening of microalbuminuria by good blood glucose control has been confirmed in Type 2 diabetes, though not at the stage of chronic renal failure (CRF). Thus, it would seem desirable to maintain strict blood glucose control whenever circumstances allow. If prescribed sulphonylureas (SU) are effective, they can be continued at adjusted doses until an advanced stage of CRF, subject to strict monitoring. SU are eliminated by the liver, but their metabolites (often active) are eliminated to varying degrees by the kidney. Non-SU insulin secretagogues and thiazolidinediones metabolised by the liver might also be used. The fate of their metabolites (some active) remains to be defined in CRF, and further clinical trials are required. Acarbose and its metabolites, as well as miglitol, very probably accumulate in CRF, causing ill-defined (but especially hepatic) iatrogenic risks. Although the danger of metformin in diabetic patients with renal failure is currently uncertain, CRF remains a regulatory contraindication. Insulin, which is necessary in most Type 2 diabetic patients with CRF, decreases as CRF progresses and when dialysis is started. The kinetics of insulin analogs are modified in CRF. Regardless of the choice of treatment, specialist and regular monitoring is required.

The Pro115Gln and Pro12Ala PPAR gamma gene mutations in obesity and type 2 diabetes.

OBJECTIVE: Peroxisome-proliferator-activated receptors gamma (PPAR gamma), is a key regulator of adipocyte differentiation and energy balance. Two naturally occurring mutations in the PPAR gamma gene, Pro115Gln and Pro12Ala, have recently been shown to impair the function of the PPAR gamma2 isoform of the receptor and to be associated with obesity or diabetes-related phenotypes in different populations. SUBJECTS: We studied the occurrence and possible associations of the Pro115Gln and Pro12Ala in the PPAR gamma2 gene with several clinical and metabolic phenotypes in three independent large populations of non-obese non-diabetic, type 2 diabetic, and morbidly obese French Caucasians. RESULTS: The Pro115Gln mutation was not found in any of the 1069 subjects screened including 626 obese patients. The frequency of the Pro12Ala mutation was similar in all groups (0.08, 0.11, 0.09) and was not associated with BMI or any of the clinical parameters tested. CONCLUSIONS: We conclude that the Pro115Gln mutation is not a frequent cause of morbid obesity in Caucasians and that the Pro12Ala mutation is not associated with clinically significant changes in these populations.

[Silent ischemic cardiopathy: which diabetics to examine?]. / Cardiopathie ischémique silencieuse: quels diabétiques explorer?

Non-Invasive coronary investigations are positive in 12 to 52% (average 22%) of type II diabetics, and 11 to 30% (average 17%) of type i diabetics. These statistics vary according to bias of recruitment. Haemodynamic lesions are found at coronary angiography in 35 to 80% of patients who have at least one positive non-invasive investigation. Nine to 12% of diabetics have silent myocardial ischaemia (SMI) confirmed by coronary angiography, compared with 1.3 to 5.3% of non-diabetic controls paired for age and sex. The higher frequency of SMI in diabetics seems to be mostly due to the increased frequency of ischaemic heart disease in diabetics. The importance of cardiac autonomic neuropathy (CAN) in SMI is controversial. The risk factors associated with SMI are those usually associated with coronary artery disease: age, masculine gender, hypercholesterolaemia, hypertriglyceridaemia, hypertension, smoking, a family history of cardiovascular disease, insulin therapy (for type II diabetes), proteinuria, retinopathy, peripheral occlusive arterial disease.... The French recommendations for investigating SMI seem to be contradictory. A single risk score in a given patient could help codify the investigation of SMI in diabetics, but this type of score has not yet been validated.

Cooperation between general practitioners and diabetologists and clinical audit improve the management of type 2 diabetic patients.

A programme was set up in the Essonne (France) between 1994 and 1998 to improve the quality of care for Type 2 diabetic patients. A consensus panel of general practitioners and diabetes specialists established guidelines based on the French St. Vincent recommendations. An audit involving 73 volunteer general practitioners (out of 965 in the Essonne) then evaluated compliance with these guidelines. Care and outcome were assessed in 505 (1995) and 604 (1996) Type 2 diabetic patients. The first audit cycle showed that defined standards were not met for several criteria and also revealed a lack of standardisation of HbA1c measurements and delayed intervention when blood glucose control was inadequate. Corrective measures were adopted: cooperative protocols for foot care, prevention of nephropathy and retinopathy, standardisation of HbA1c, and an educational programme at the primary health care level. The second audit cycle showed improvement in foot care (+33.6%), quality (+39.9%), prescription of HbA1c (+11.9%), and control of blood pressure (+11.9%) and blood lipids (+12.8%). The proportion of early interventions in case of inadequate glucose control increased significantly (+10.5%). However, some gaps persisted, mainly regarding screening for complications, diet counselling and patient education. This study shows that cooperation between general practitioners and diabetes specialists is feasible and effective in the context of a district-wide approach, and that it facilitates the adoption of international guidelines by local physicians. A project has been developed to provide structured diabetes care in general practice and better access to specialist services in order to improve the outcome of Type 2 diabetic patients.

[Role of beta blockers as the only therapy for preparing the hyperthyroid patient for surgery]. / Place des béta-bloquants comme seule thérapeutique pour préparer les hyperthyroïdiens à la chirurgie.

Indications and contraindications of the beta blocking drugs are reviewed as a method of preparation to sub total thyroidectomy in thyrotoxicosis. They allow a shorter preparation's time: a few days, until one or two weeks maximum. Major risks are cardiac failure, and altered response to stress. This technic is contraindicated in thyrocardiac disease, severe thyrotoxicosis and for patients over fifty years of age. The best beta blocking's criterion is exercise-induced tachycardia's reduction. The safety of this method allows its utilisation when social, medical or psychological environment requires a quick thyrotoxicosis' recovery.

[Interest and limits of beta blocking drugs for preparing Grave's disease to sub-total thyroidectomy (author's transl)]. / Intérêt et limites des bêta-bloquants pour la préparation des maladies de Basedow a la thyroidectomie sub-totale.

The use of beta blocking drugs as a preparation to the sub-total thyroidectomy in Graves's disease allows to shorten the pre-operation time. However, besides the observance of classical contraindications, it requires that patient who remain hyperthyroid are closely looked after. Within these limits, it seems to be quite useful for patients who need to quickly come back to euthyroid status.