Value and limitations of the Continuous Glucose Monitoring System in the management of type 1 diabetes.

The CGMS (Continuous Glucose Monitoring System) is a portable device allowing continuous measuring of glucose. It provides recordings of at least 72 h, during which 288 measures/day are performed. Results are visualised in the form of a set of curves, illustrating the variations in blood glucose levels over time. The quality of the records has often been questioned by several authors. Some of the system's physiologically related limitations can be explained by the less than perfect coincidence of variations in glucose levels observed in the interstitial tissue, where CGMS measurings are done, and in the blood, where calibrations are performed. Other limitations, such as defects in accuracy or in reproducibility of tracings or premature curtailments of recordings, are due to technical weaknesses which were considerably improved during the past few years, particularly with regard to the quality of the electrodes providing a more stable signal over time. In clinical practice, CGMS is a tool for investigating the glycaemic patterns of diabetic patients in conjonction with SMBG. It allows the identification of overlooked hyper- or hypoglycaemia. Generally well accepted, it is a usefull tool to analyse the nocturnal period, or any situation where glucose checks are rare. The visual nature of its results provides a facilitating support in the discussion between the patient and the care-provider during consultations or educational sessions. CGMS utilisation was proposed for guiding treatment adjustment. At present, it is still difficult to state with certainty that this tool allows effective improvement in the metabolic control of patients with type 1 diabetes, in view of the paucity of controlled studies showing an impact on HbA1c values or on the frequency of hypoglycaemia, even if such a tendency emerges from most non-controlled intervention trials.

Insulin initiation in type 2 diabetic patients admitted in hospital in France and follow-up at 1 year.

OBJECTIVES AND METHODS: The IDAHO 2 epidemiological survey was conducted in departments of diabetology in insulin-naïve type 2 diabetics for whom insulin was initiated. The objective was to assess the patients' profile, the treatments proposed during hospital stay and after one year. RESULTS: 797 patients were analysed. Their characteristics were: age 64+/-12 years, 49% males, weight: 78+/-17 kg, BMI: 29+/-6 kg/m2, diabetes duration 11 years, prevalence of complications: 68%, fasting blood glucose 13+/-6 mmol/l, HbA1c: 10+/-2.2%; treatment prior to insulin comprised: at least 2 OHA: 71% of cases, one: 21%, no OAD: 8%. At hospital discharge, 54% of the patients used basal insulin. After 1 year, 670 continued on insulin. The insulin initiation was accompanied by a decrease in the FBG level (baseline: 13+/-6 mmol/l; final: 8.5+/-2.75 mmol/l; P<0.0001) and a HbA1c improvement (baseline: 10+/-2.2%; final: 7.9+/-1.4%; P<0.0001). This was observed du-ring the first 6 months (HbA1c: 7.8%, P<0.0001 versus baseline). 80% of the patients remained on the same insulin regimen after 1 year: 35% had 1 injection/day, 44% had 2, 12% had 3 and 9% had a complex regimen. The weight gain, the final daily dose and hypoglycaemias increased with the number of injections. The mean daily insulin dose was 33 U/day (24 U with 1 injection/day). CONCLUSION: The IDAHO study shows that insulin is effective in type 2 diabetics however, management is inadequate with insulin therapy being initiated too late and at doses which are low after one year.

Metabolic syndrome is associated with markers of subclinical atherosclerosis in a French population-based sample.

Metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease (CVD). The relation of MetS with early stages of atherosclerosis, more important from a prevention perspective, has not been evaluated extensively. We examined the association of MetS, using WHO and NCEP definitions, with number of carotid and femoral plaques; carotid intima-media thickness (IMT); pulse wave velocity (PWV) in a random population-based sample of 1153 French adults (35-65 year). Impact of inflammatory factors (C-reactive protein and soluble intercellular adhesion molecule-1) on these parameters was also evaluated. Prevalence of MetS was 14.5 (CI: 12.3-16.0) and 17.5 (CI: 15.1-20.2)%, using NCEP and WHO definitions, respectively. MetS significantly predicted number of plaques, IMT, and PWV after adjustment for traditional risk factors (P<0.05). Inflammatory factors predicted peripheral plaques only. The risk of subclinical atherosclerosis was considerably increased with MetS (P<0.05); odds ratios ranged 1.80-2.15 with NCEP definition, and 1.48-1.97 with WHO definition. Individuals meeting both NCEP and WHO definitions had slightly greater risk of increased plaques, IMT, and PWV. MetS was strongly associated with subclinical atherosclerosis and aortic stiffness, and can be used as a surrogate marker for high CVD risk, deserving aggressive treatment.

Advantages to using capillary blood beta-hydroxybutyrate determination for the detection and treatment of diabetic ketosis.

Ketone body determination is indicated in all diabetic patients when the risk of ketotic decompensation exists. New methods of screening for ketosis, in particular capillary blood ketone body determination, provide analytical, technical and clinical advantages compared to the conventional ketonuria. It is proposed that a diabetic patient with hyperglycaemia (capillary blood glucose > 2.50 g.l(-1)) and capillary blood ketone bodies exceeding 0.5 mmol.l(-1) requires therapeutic management. For values greater than 3 mmol.l(-1) or in case of more serious clinical symptoms, hospitalisation is indicated, considering the high probability of ketoacidotic decompensation. The advantages of capillary blood ketone body determination including easy use, and rapid and objective results may improve management of the diabetic patient, especially in emergency situations. However, prescription by a physician of capillary blood ketone body determination should be offered to targeted populations that have a high risk of ketoacidotic decompensation, after providing education to patients that is above all aimed at preventing this metabolic complication. In this context of determining ketone bodies in capillary blood, the term "capillary blood ketone bodies" is therefore preferable to the term "capillary blood beta-hydroxybutyrate determination". Indeed, it appears more appropriate, simple, descriptive and significant both for health-care staff and for patients.

Reproducibility and variability in the action of injected insulin.

Insulin-treated patients are generally taught to adapt their doses of insulin according to the glycemic level obtained during self-tests. They usually adhere to medical recommendations, but are often confused by the results, which may not correspond to expectations. Patients have to contend with variability and a certain degree of unpredictability in the results. Our knowledge of the factors involved in this variability is often imprecise. We review here the factors depending on the preparation of insulin itself, not only with regard to its crystallization but also the speed at which the hexamers dissociate into dimers. The development of fast and slow-acting analogues is discussed along with their value in improving glycemic predictability. In addition to these factors, we mention those stemming from the injection technique itself, which are directly related to the instructions given to the patients. For crystallized insulin preparations, shaking the bottle is an important element that the development of slow-acting analogues should eliminate, but the time lapse before withdrawing the needle, the anatomical site of the insulin injection, and the depth of the injection are also factors for variability. Greater predictability in the action of insulin will be obtained from a combination of progress in manufacturing procedures and better patient education.

What are capillary blood ketone levels in type 1 diabetic patients using CSII in normal conditions of insulin delivery?

OBJECTIVE: The aim of the study was to determine the normal level of capillary ketonemia in type 1 diabetic patients on continuous subcutaneous insulin infusion (CSII). RESEARCH DESIGN AND METHODS: A total of 36 type 1 diabetic patients treated by external pump were studied for 2 to 3 weeks. Patients were instructed to self monitor capillary glucose and capillary ketone bodies at least 4 times per day with a handheld Medisense Optium meter and check for urinary ketone bodies in the morning and when blood glucose exceeded 2.5 g/l with a semiquantitative test. Data were collected and analysed for each period of time defined as the time interval between two changes of the infusion site. A period was considered "normal" when no problem causing any impairment in insulin delivery was detected. RESULTS: 186 periods of 2.1 +/- 0.9 days were recorded; 119 were considered normal. 1281 coupled values of glucose and betahydroxybutyrate were analysed during the so called normal periods. Mean percentage of ketonemia of 0, 0.1, 0.2, > or =0.3 mmole/l were 81.3%, 13%, 3.7% and 2% respectively whereas mean glucose level (g/l) was 1.49 +/- 0.7, 1.48 +/- 0.7, 1.59 +/- 0.8 and 1.89 +/- 0.9 respectively. Only 0.9% of betahydroxybutyrate values were > or =0.3 mmole/l when blood glucose exceeded 2.5 g/l. CONCLUSION: Our study indicates that ketonemia self monitoring can be a valuable tool to screen insulin deficiency in patients on CSII with a low risk of false positive if we consider a threshold of 0.3 mmole/l for ketone bodies.

[Implementation of the "Diabetes Prevention Program", in Europe]. / Mise en oeuvre du Diabetes Prevention Program en Europe.

Prevention of type 2 diabetes has been a major issue for healthcare providers because of the high incidence and the high cost of diabetes. High cost is related to diabetes treatments, diabetes complications and the reduction of lifetime expectancy. The Diabetes Prevention Program study has recently shown that the prevention of diabetes is possible in patients with impaired glucose tolerance. In this study, diabetes was prevented either by metformin or by intensive lifestyle changes. Intensive lifestyle changes were even more effective than metformin in preventing diabetes. This article discusses how difficult it would be to implement this program in Europe. The difficulties would be both practical (identification of the high risk population, patients' motivation for intensive lifestyle changes) and economic. The implementation of the program in Europe would be theoretically cost-effective but would be technically very hard to do.

[Insulin therapy and self-monitoring of blood glucose: therapeutic management and recommendations]. / Insulinothérapie et autosurveillance glycémique: schéma thérapeutique et recommandations.

Self-monitoring of blood glucose (SMBG) has been widely spread during the last twenty years, and is at present considered as mandatory for the management of insulin therapy. The ALFEDIAM and the ADA recommend type 1 diabetic patients to perform more than 4 capillary glucose determinations per day, ideally 4 to 6. To be efficient in using these results, several parameters are required: glycemic targets have to be clearly defined, an intensified insulin regimen (3 or 4 injections per day or insulin pump therapy) should be proposed, and the patient should be teached how to modify his insulin doses. Short acting insulin analogs are available, and long acting insulin analog will be soon. This is a real progress in the choice of flexible insulin regimen. The practice of SMBG and its use for insulin adjustment requires continuing education, in order to translate SMBG in real diabetes self-management. This prerequisite is mandatory to obtain a sustained improvement in metabolic control.

[Healthcare networks: involvement of various healthcare professionals]. / Les réseaux de soins: multidisciplinarité et équipe.

Diabetes is a very representative model of chronic disease requiring a partnership between various healthcare professionals. The organisation of healthcare networks allows a global care improvement. For the "Midi-Pyrénées" area, the diabetes network associates physicians and other healthcare professionals, working in their private - practice or in clinics or hospitals. The priority of this network was to develop therapeutic patient education, outdoors and indoors. The use of a specific communication system will be unavoidable, as a basis for medical files, evaluation, and permanent updates for the network members. Current projects concern a regional organization for chronic foot ulcers care, coronary heart disease and diabetes during pregnancy. These various care domains suppose the collaboration with other regional networks.

Intensified treatment of type 1 diabetes: prospective evaluation at one year of a therapeutic patient education programme.

BACKGROUND: Type 1 diabetes treatment requires not only an intensive insulin regimen, but also intensive management, which daily involves participation of the patient. Our aim was to prospectively evaluate the efficacy on patient skills and metabolic control of our routine 5-day in-patient education programme. METHODS: Over one year, each type 1 diabetic patient undertaking the programme for the first time, and able to complete a 2, 6, and 12 month follow-up, participated in the study (n=76). At baseline (T0), 61 patients had intensified insulin treatment and 15 increased from 2 to 3 daily insulin injections during the hospital stay. Using questionnaires and analysis of a glycaemia logbook, we evaluated at T0, T2, T6 and T12 patient skills related to diet, physical exercise, self-monitoring of blood glucose (SMBG), adjustment of insulin doses, and treatment of hypoglycaemia. Metabolic control was evaluated at the same time. RESULTS: At one year, the following skills improved: Intake of carbohydrates (T0: 59%, T12: 90% of patients, p<0.001) and snacks (p<0.001), appropriate physical exercise (p<0.001), frequency of SMBG (T0: 3.3 +/- 1.5/day, T12: 4.5 +/- 1/day, p<0.001), frequency of post-prandial tests (p<0.001) and adjustment of insulin doses (T0: 18%, T12: 53% of patients, p<0.001). More patients always carried sugar (T0: 61%, T12: 97%, p<0.001) and appropriately treated hypoglycaemia (T0: 48%, T12: 79%, p<0.001). Concurrently, HbA(1c) decreased (T0: 8.6 +/- 1.5%, T12: 7.7 +/- 0.9%, p<0.001), and the frequency of hypoglycaemia was reduced (p<0.001). There was a correlation between the decrease of HbA(1c) and the frequency of SMBG (p<0.001, r2=0,24). CONCLUSIONS: Education led to positive changes in patient skills, which were maintained over one year and were associated with improved metabolic control.

[Indication of CGMS (Continuous Glucose Monitoring System) in the functionnal investigations of adult type 1 diabetic patients]. / Intérêt du CGMS (Continuous Glucose Monitoring System) dans l'exploration du diabète de type 1 de l'adulte.

The Minimed CGMS (Continuous Glucose Monitoring System) is a holter-style electroenzymatic sensor allowing 3-days continuous monitoring of interstitial glucose fluctuations. This device gathers wide informations about the fluctuations of glucose over the day, in a more detailed (288 measurements) but less accurate way than those obtained from glucose self-monitoring. Its utilisation has been proposed for the analysis of nocturnal glucose control, to detect asymptomatic hypoglycemia or dawn phenomenon, and could be useful in the adjustment of type 1 diabetes therapy. Thus, its use could contribute to an improvement in glucose control, especially in patients with low compliance to self-monitoring. CGMS graphs can be used as an individual teaching support, or illustrate characteristic situations during collective educational sessions. The period chosen for the CGMS record, the duration of the record and the instructions given to the patients are of major importance to obtain accurate and reproductive graphs, that can be used in clinical practice.

[Microalbuminuria, pulse wave velocity and common carotid artery intima-media thickness in type 2 diabetes]. / Microalbuminurie, vitesse d'onde de pouls et épaisseur intima-média carotidienne chez le patient diabétique de type 2.

The aim of the study was to evaluate pulse wave velocity (PWV) and carotid intima-media thickness (IMT) in type 2 diabetics with microalbuminuria (mualb). The study concerned 37 patients type 2 diabetics, age: 53.4 +/- 6.6, years free of cardiovascular complications. HbA1C was 7.73 +/- 1.39%, waist circumference 104.2 +/- 11.7 cm. 19 patients with BP > 130/85 mmHg were identified as mild hypertensives (17/19 under treatment). All patients underwent ABPM, PWV and IMT measurements. The study population was separated into 2 subgroups according to median of mualb (mg/24 h): 18.9. [table: see text] In patients with mualb > 18.9 mg/24, IMT and PWV were significantly increased (p = 0.06; p < 0.01). After adjustment to BP and age, there was no significant difference in IMT and PWV in the subgroups. In this selected population of type 2 diabetics, microalbuminuria appears associated to a pressure-dependant vascular remodeling.

Therapeutic perspectives for type 2 diabetes mellitus: molecular and clinical insights.

Current antidiabetic agents do not suppress insulin resistance, do not reinstate physiological insulin secretion and fail to prevent the gradual loss of B-cell function. Thus, these molecules are unable to maintain long term euglycemia in all type 2 diabetic patients and there is a need for new antidiabetic drugs. Thiazolidinediones (TZD) are a new class of insulin sensitizers recently approved in Europe, in combination therapy with sulfonylureas or/and metformin, for the treatment of type 2 diabetes. TZD show beneficial effects on insulin action, glucose homeostasis and lipid metabolism despite a substantial weight gain. Their potential protective effect on B-cell function and on the development of macrovascular complication is of particular interest. Non TZD PPARgamma agonists are also under clinical trials. Other interesting therapeutic perspectives to treat insulin resistance lie in the development of inhibitors of protein tyrosine phosphatases and in the promotion of non insulin-dependent contraction-like muscle glucose uptake via stimulation of AMP protein kinase (AMPK). As to new insulin secretagogues, the phenylalanine derivative nateglinide is a first phase insulin secretion enhancer primarily intended at controlling post-prandial hyperglycemia. The most promising perspective to improve B-cell function lies in the development of glucagon-like peptide-1 (GLP-1) analogs. Clinical studies show beneficial effects on glucose homeostasis in type 2 diabetics and efficacy in sulfonylurea resistant patients without risk of hypoglycaemia. Animal studies predict beneficial effects on B-cell mass. Finally we will discuss the potential use of gene therapy to treat insulin resistance and B-cell dysfunction.

Evaluation of microcomputer nutritional teaching games in 1,876 children at school.

OBJECTIVE: We evaluated in a prospective study microcomputer nutritional teaching games and their contribution to the children's acquisition of nutritional knowledge and improvement of eating habits. MATERIAL AND METHODS: One thousand eight hundred seventy-six children aged 7-12 years took part in this study at school. All 16 schools of the same school district were randomized into two groups: games group and control group, both receiving conventional nutritional teaching by their teachers. The children in the games group played computer games during the conventional nutritional teaching period (2 hours a week for 5 weeks). At completion of the study, dietetic knowledge and dietary records were evaluated in both groups. RESULTS: Dietary knowledge tests results were better in the games group (p<0.001). The children in the games group had a significantly better balanced diet for an energy intake of about 1900 kilocalories: more carbohydrate (46.4 +/- 0.2% vs 45.7 +/- 0.2%, p<0.05), less fat (37.1 +/- 0.1% vs 37.6 +/- 0.2%, p<0.05), less protein (16.5 +/- 0.1% vs 16.7 +/- 0.1%, p<0.05), less saccharose (11.5 +/- 0.1% vs 12.2 +/- 0.2%, p<0.001), more calcium (p<0.001) and more fiber (p<0.05). The games group had a better snack at 10 a.m., a less copious lunch and less nibbling (p<0.001). CONCLUSION: The children in the games group had slightly but significantly better nutritional knowledge and dietary intake compared to children in the control group. Using our micro computer nutritional teaching games at school provides an additional and modern support to conventional teaching.

Prevalence of type 2 diabetes and impaired fasting glucose in the middle-aged population of three French regions - The MONICA study 1995-97.

OBJECTIVES: The aim of this study was to determine the prevalence of type 2 diabetes and impaired fasting glucose (IFG) in a population-based sample of 3 508 subjects, aged 35-64 years, participating in the French MONICA population survey from 1995 to 1997 in three French regions: the Urban Community of Lille, the Bas-Rhin and the Haute-Garonne. MATERIAL AND METHODS: Previously diagnosed type 2 diabetes is defined by the current use of oral hypoglycaemic treatment and newly diagnosed subjects by fasting plasma glucose (FPG) > or =7.0 mmol/L according to the ADA 1997 recommendations. IFG was determined by 6.1< or =FPG< or =6.9 mmol/L. Adjusted prevalences are calculated according to the French 1990 census data. RESULTS: Type 2 diabetes adjusted prevalence is 5.1% [4.1-6.1] in women and 7.3% [6.1-8.4] in men while IFG adjusted prevalence is 5.2% [4.2-6.2] and 11.8% [10.3-13.4] respectively. Prevalences of type 2 diabetes and IFG are both significantly higher in men than in women. This trend appears in any age group for IFG, but is only observed in 55-64 year-old subjects for type 2 diabetes. The reduction of the FPG threshold to screen diabetes mellitus from 7.8 to 7.0 mmol/L according to the ADA recommendations results in a 2.2-fold increase in the number of newly diagnosed diabetic subjects, screened by one FPG measurement, in our population-based sample. CONCLUSIONS: The MONICA population survey confirms that type 2 diabetes represents a major health care problem in France and underlines the influence of gender on the prevalence of both type 2 diabetes and IFG in the French middle-aged population.

Multicenter randomized evaluation of a nutritional education software in obese patients.

OBJECTIVE: To study the efficacy of the nutritional education software, Nutri-Expert, in the management of obese adult patients. MATERIAL AND METHODS: Two groups of obese patients were followed up over one year in a randomized study: the first group received close traditional management (seven nutritional visits over the year, with physicians and dietitians conjointly) and the second one also used at home by Minitel the Nutri-Expert system. 557 patients were enrolled in the study by 16 French centers of diabetology and nutrition. Body mass index (BMI), tests of dietetic knowledge, dietary records and centralized biological measurements were assessed at inclusion, 6 and 12 months. 341 patients were evaluable at the end of the year. RESULTS: The group using Nutri-Expert scored significantly better in the tests of dietetic knowledge than the control group. For all patients, nutritional education led to a significant improvement in BMI, dietary records and biological measurements, without significant difference between the two groups. Five years after the end of the study, the weight of 148 patients was recorded; mean BMI was significantly lower than the initial value but there was no significant difference between the two groups. CONCLUSION: In the management of obese patients, Nutri-Expert system has a role to play in reinforcing nutritional knowledge; if regular follow-up is not possible, or if a large series of obese patients is to be treated, Nutri-Expert could partly replace traditional management, for example between visits.

[Diabetic foot]. / Le pied diabétique.

Diabetic foot ulcers are a frequent and severe complication of diabetes mellitus. A multidisciplinary approach (in-patient and out-patient care) improves prognosis and reduces the amputation rate. Risk factors are well defined and easily identified. High-risk patients (sensory loss, vascular disease, previous ulcer, foot deformities) have to be detected. In France, comprehensive foot-care programs, including education and regular foot examination, must be developed. The reduction of the economical and human burden needs the urgent formation of more multidisciplinary teams (to take care of patients properly and very early), foot care networks, and prevention programs.

[Is cardiovascular risk different in the diabetic woman?]. / Le risque cardiovasculaire est-il différent chez la femme diabétique?

Cardiovascular disease is a leading cause of mortality among diabetic women. However, studies devoted to cardiovascular disease in women, and particularly diabetic women, are scarce. Diabetes erases the natural protection of premenopausal women against cardiovascular disease. Risk of death from coronary artery disease is higher in diabetic women than in diabetic men. Diabetic women might be more exposed to some risk factors. Non invasive diagnostic tools of coronary artery disease are less accurate in women, and women are less likely than men to undergo catheterization or revascularization. The lower diameter of coronary artery might contribute to these reluctances. Nevertheless, long-term outcome of the revascularization procedures (thrombolysis, bypass graft, angioplasty) are similar in men and women, although peri-procedural risks might be higher in women. Finally, secondary prevention treatments, particularly beta-blockers, are underused in women. Gender differences in cardiovascular risk among diabetics are partly explained by discrepancies in terms of coronary artery anatomy or lack of reliable non invasive tests. But the longer delay to treatment and the lack of scientific information about the particular features of coronary heart disease in women probably contribute to the increased risk in diabetic women.

Comparison of continuous subcutaneous insulin infusion and multiple daily injection regimens using insulin lispro in type 1 diabetic patients on intensified treatment: a randomized study. The Study Group for the Development of Pump Therapy in Diabetes.

OBJECTIVE: To compare the efficacy of 2 intensified insulin regimens, continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI), by using the short-acting insulin analog lispro in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 41 C-peptide-negative type 1 diabetic patients (age 43.5+/-10.3 years; 21 men and 20 women, BMI 24.0+/-2.4 kg/m2, diabetes duration 20.0+/-11.3 years) on intensified insulin therapy (MDI with regular insulin or lispro, n = 9, CSII with regular insulin, n = 32) were included in an open-label randomized crossover study comparing two 4-month periods of intensified insulin therapy with lispro: one period by MDI and the other by CSII. Blood glucose (BG) was monitored before and after each of the 3 meals each day. RESULTS: The basal insulin regimen had to be optimized in 75% of the patients during the MDI period (mean number of NPH injections per day = 2.65). HbA1c values were lower when lispro was used in CSII than in MDI (7.89+/-0.77 vs. 8.24+/-0.77%, P<0.001). BG levels were lower with CSII (165+/-27 vs. 175+/-33 mg/dl, P<0.05). The SD of all the BG values (73+/-15 vs. 82+/-18 mg/dl, P<0.01) was lower with CSII. The frequency of hypoglycemic events, defined as BG levels <60 mg/dl, did not differ significantly between the 2 modalities (CSII 3.9+/-4.2 per 14 days vs. MDI 4.3+/-3.9 per 14 days). Mean insulin doses were significantly lower with CSII than with MDI (38.5+/-9.8 vs. 47.3+/-14.9 U/day. respectively, P< 0.0001). CONCLUSIONS: When used with external pumps versus MDI, lispro provides better glycemic control and stability with much lower doses of insulin and does not increase the frequency of hypoglycemic episodes.