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Biomedical subjects

L Monnier

Publications and source records attributed to L Monnier.

At least 19 recordsLinked to original sources

Addition of rapid-acting insulin to basal insulin therapy in type 2 diabetes: indications and modalities.

There are many reasons to believe that in the near future, the treatment of patients with Type 2 diabetes will be characterised by an increased use of insulin therapy. To ensure that insulin regimens are acceptable to patients, and implemented by physicians, they should be as simple and efficient as possible. Simplicity is synonymous with the regimen of once-daily basal insulin glargine given at any time of the day (at the same time each day). With such a strategy, the dose is adjusted by titrating to target fasting blood glucose values of 5.0 - 7.2 mmol/L (90 - 130 mg/dL). When these targets can no longer be achieved with reasonable doses of long-acting insulin, a rapid-acting insulin analogue should be added at meal times. A step-by-step strategy can be used; it is recommended that initially, a single daily prandial bolus of a rapid-acting insulin analogue is administered before the meal that leads to the highest post-meal blood glucose excursions. Further boluses can be added at other meal times as necessary, i.e, when post-meal blood glucose values remain above 10.0 mmol/L (180 mg/dL) and 7.8 mmol/L (140 mg/dL) at mid-morning and 2h-post-lunch or post-dinner times, respectively. This stepwise strategy may eventually lead to a standard basal-bolus regimen with 3 pre-meal injections of rapid-acting insulin analogues, a potentially small trade-off for achieving fairly-well controlled diabetes.

Blood Glucose↗

Insulin secretion and sensitivity as determinants of HbA1c in type 2 diabetes.

BACKGROUND: Defects in insulin secretion and sensitivity, two major determinants of glycaemic control, can occur and progress or not in parallel. The present study was designed to compare the respective roles of both determinants on HbA1c, in type 2 diabetic patients, according to whether or not residual beta-cell function was stimulated with insulin secretagogues. MATERIALS AND METHODS: Insulin secretion and insulin sensitivity were both estimated using the homeostasis model assessment (HOMA). HbA1c, insulin sensitivity (HOMA2%S) and insulin secretion (HOMA2%B) were determined in 289 noninsulin-using type 2 diabetic patients who were further divided into two groups according to treatment: metformin alone (group I, n = 57) or metformin and glyburide (group II, n = 232). The patients of both groups were further divided into three subsets in order to test the dependence of HbA1c on HOMA2%B and HOMA2%S. RESULTS: In group I mean HbA1c were greater (8.4%) in patients with HOMA2%B < 50% than in the two subsets with HOMA2%B > or = 50%: 7.2 and 6.8% (P = 0.0013). In group II mean values of stimulated-insulin secretion (HOMA2%B) were lesser (40.7 and 30.1%) in the two subsets of patients with HbA1c > or = 8% than in patients with HbA1c < 8%: 55.1% (P < 0.0001). By contrast, we found no differences in both groups with HOMA2%S. A stepwise multiple regression showed that HOMA2%B contributed to HbA1c more than HOMA2%S both in groups I (33.5% vs. 23.4%) and II (22.7% vs. 8%). CONCLUSIONS: Although the role of insulin sensitivity is not negligible, insulin secretion appears to be the major determinant of diabetic control in overt type 2 diabetic patients who are treated with metformin alone or with a two-drug therapy combining metformin and glyburide.

Biomarkers↗

An overview of the rationale for pharmacological strategies in type 2 diabetes: from the evidence to new perspectives.

Therapeutic strategies in type 2 diabetic patients should not only integrate both the targets and indications of the different therapies but should be also a compromise between the patient's and physician's goals and willingnesses. The rationale for therapeutic targets is based on recommendations that differ from one country to another. Even though HbA1c remains the "gold standard", monitoring of blood glucose at fasting and postprandial time-points is a complementary tool for estimating both the quality and safety of diabetic control. Despite the lack of available strong evidence-based data it seems that achieving glucose levels < 130 mg/dl at fasting and < 180 mg/dl or < 140 mg/dl over postbreakfast or postlunch periods, respectively, might be a reasonable goal in most countries. The choice of appropriate strategies for treating type 2 diabetic patients should ideally be based on pathophysiological considerations. However for practical reasons, decisions for initiating or completing antidiabetic treatments are usually made by using such simple parameters as HbA1c and plasma glucose levels. The bridge between pathophysiological and clinical rationales can be obtained from the analysis of the relative contributions of fasting and postprandial glucose to the overall hyperglycaemia. In patients with HbA1c < 7.3%, postprandial glucose makes the major contribution to the overall hyperglycaemia, whereas the contribution of fasting glucose becomes progressively predominant in patients with HbA1c > 7.3%. As a consequence of these observations, initiation of antidiabetic treatments or implementation of second-line therapies should be aimed at reducing either postprandial excursions or fasting hyperglycaemia according to whether HbA1c levels are found respectively below or above a cut-off value of 7.3%.

Blood Glucose↗

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.

3-Hydroxybutyric Acid↗

A thromboxane effect of a hydroxytyrosol-rich olive oil wastewater extract in patients with uncomplicated type I diabetes.

OBJECTIVE: To assess the antioxidant/non-antioxidant effects of a hydroxytyrosol (HT)-rich phenolic extract from olive mill wastewaters administered with a breakfast. DESIGN, SETTING AND SUBJECTS: Five type I diabetic patients received 25 mg of HT the first day and 12.5 mg/day the following 3 days. Blood sampling was carried out at T(0) (baseline) and T(4d) just before the breakfast + HT administration and at time points 1, 2, 3 and 4 h after T(0). Urines (24-h) were collected from T(0) to T(4d). Baseline HbA1c was generally inferior to 10%, glycemia was within the range 6-24 mmol/l, whereas total cholesterol, HDL-chol and triglycerides were normal. RESULTS: The major finding was the 46% decrease in the serum TXB(2) production after blood clotting at T(4d). Plasma vitamin A, E, beta-carotene were not changed. Vitamin C tended to increase (P = 0.075). Plasma antioxidant capacity was enhanced at T(0)+1 h only, whereas its main determinants (albumin, bilirubin, uric acid) were not modified. Urinary 8-isoPGF(2alpha) levels were highly variable and were not affected significantly by HT administration. CONCLUSION: The major effect of HT accounts for an antiaggregating platelet action, leading to a possible prevention of thrombotic and microthrombotic processes.

Adult↗

Dichotomous responses of inter and postprandial hyperglycaemia to short-term calorie restriction in patients with type 2 diabetes.

BACKGROUND: In type 2 diabetes the effects of short-term calorie restrictions on glycaemia are usually judged on fasting plasma glucose. As fasting duration rarely exceeds 2-3 h, we determined the effects of calorie restriction over different daytime periods using a continuous glucose monitoring system (CGMS) in noninsulin-using patients with type 2 diabetes. DESIGN: Fourteen poorly controlled (mean HbA1c = 9.3%) overweight or obese patients (mean body mass index = 30.1 +/- 0.7 kg m(-2)) with type 2 diabetes were investigated twice with a CGMS, at baseline and at the end of a 18-day calorie-restricted diet (1490 kcal day(-1)). Areas under curves (AUCs) of 24-h glucose monitoring were measured and divided into postprandial and interprandial AUCs according to meal times. RESULTS: Areas under curves of 24-h glucose monitoring were significantly decreased after dieting: -37%, P = 0.0047. Both post and interprandial AUCs were significantly diminished (-26%, P = 0.0186 and -48%, P = 0.0037, respectively), but changes in interprandial AUCs were more marked than changes in postprandial AUCs (P = 0.0060). Nycthemeral peaks of glucose were observed at mid-morning times and were not significantly different before (242 +/- 15 mg dL(-1)) and after dieting (227 +/- 16 mg dL(-1)). CONCLUSIONS: Short-term calorie restriction in overweight or obese patients with type 2 diabetes resulted in dichotomous responses between interprandial and postprandial glycaemic excursions. The resistance of mid-morning glucose peaking to calorie restriction should result in additional dietary or pharmacological measures at breakfast.

Area Under Curve↗

[Pioglitazone insulin sensitivity and type 2 diabetes mellitus: recent data].

Thiazolidinediones ("glitazones") were recently added to the oral treatment of type 2 diabetes. Two glitazones are available in France, pioglitazone and rosiglitazone, which progressively were granted broader therapeutic indications since their launch in 2002. This review presents the most recent pioglitazone pharmacological and clinical data, with a particular emphasis on the QUARTET clinical study program results. Available information generates perspectives and hopes: prevention of the progressive decline in beta-pancreatic cell function (and possibly, prevention of type 2 diabetes in at-risk subjects), cardiovascular prevention in type 2 diabetic patients depending on the results of the ongoing prospective morbi-mortality studies in high risk type 2 diabetic patients.

Diabetes Mellitus, Type 2↗

Management of French patients with type 2 diabetes mellitus in medical general practice: report of the Mediab observatory.

OBJECTIVES: The Mediab study was conducted to estimate the medical care in French patients with type 2 diabetes mellitus managed by general practitioners on an ambulatory basis, but consIdered as requiring new treatment implementation. METHODS: Five thousand one hundred and fourty eight diabetic patients without any treatment or treated with lifestyle measures either alone or combined with an oral antIdiabetic agent given as monotherapy were included in a cross-sectional study that was conducted on a nationwIde basis by using the ORP (R) methodology. The 4088 patients in whom HbA1c was determined with a reliable method were further classified into 3 categories according to whether HbA1c was<=6.5% (group I, n=525), ranging between 6.6 and 8% (group II, n=1699) or > 8% (group III, n=1864). RESULTS: A large proportion of patients (45.6%) exhibited HbA1c > 8%. Adherence to diet and regular physical activity were progressively decreasing while prevalence of diabetic complications was steadily increasing from group I to III, i.e. when diabetic control was worsening. The complications suffered from severe "underreporting". When complications were reported, the odds-ratio analysis showed that retinopathy is influenced by both the magnitude of glucose excess and the diabetes duration, while renal diseases and macroangiopathy depend mainly on diabetes duration. 38.1% of patients visited a diabetologist, but most of these patients were referred to the speciaList after the inclusion visit. CONCLUSIONS: Despite the development of guIdelines, a large percentage of patients remains poorly-controlled. Future actions should be based on: (i) better collaboration between general practitioners and diabetologists (ii) better detection of complications that suffer from severe "underreporting", (iii) reinforcement of lifestyle recommendations and of pharmacological treatments by shifting from mono- to multi-drug therapy, at earlier stages of the disease.

Age of Onset↗

Self-monitoring of blood glucose in diabetic patients: from the least common denominator to the greatest common multiple.

Self-monitoring of blood glucose (SMBG) is recognized as necessary in insulin-treated diabetic patients. There is less evidence for the regular use of SMBG in non-insulin-using type 2 diabetic patients. The rationale for an appropriate regimen of SMBG might be to have at least one time-point of monitoring included within each of the 3 periods of daytime i.e. fasting, postprandial and postabsorptive periods. Interventional trials have indicated that a 4-to 5-point daily profile represents an optimal regimen for SMBG in type 1 diabetic patients with satisfactory diabetic control. This type of SMBG includes 4 daily glucose determinations (3 before each meal and one at bedtime) and one weekly monitoring at 3: 00 am. However additional determinations should be made within postprandial states, particularly when rapid insulin analogues or pump-treatments are used. In non-insulin-using type 2 diabetic patients, studies of diurnal glycemic profiles have indicated that postprandial glucose is an important contributor to HbA1c and that mid-morning hyperglycemia is the "weakest link" of metabolic control. Therefore mid-morning glucose testing should be recommended when HbA1c levels are not correctly controlled. Furthermore, extended postlunch determinations at 5: 00 pm can be helpful for checking both the quality and safety of diabetic control in such patients. The frequency and timing of SMBG depend both on the type (1 or 2) of diabetes and should be a compromise between optimal and minimal regimens.

Blood Glucose↗

Global assessment for quality and safety of control in type 2 diabetic patients.

BACKGROUND: HbA1c (glycated haemoglobin) suffers from obvious limitations in type 2 diabetic patients at risk of hypoglycaemia or requiring rapid therapeutic adjustments. This study was conducted to discern whether the monitoring of one particular plasma glucose (PG) value of the diurnal profile can be used in such situations. DESIGN: Four diurnal PG concentrations (at 08:00, 11:00, 14:00 and 17:00 h) were measured in standardized conditions in 480 (246 men, 234 women) noninsulin-using type 2 diabetic patients. Sensitivities for predicting treatment success, i.e. HbA1c<7%, with a specificity > or =90% were calculated and compared using receiver-operating characteristic (ROC) curves. RESULTS: The probabilities (areas under ROC curves) for predicting HbA1c<7% were significantly higher at 11:00, 14:00 and 17:00 h than at 08:00 h. The optimal PG cut-off values for predicting treatment success were, respectively, 6, 9, 7 and 6 mmol L(-1) at 08:00 h, 11:00, 14:00 and 17:00 h. In most patients the lowest PG values of the diurnal profile were at 17:00 h, and 17.5% of the patients with HbA1c<7% (54.5% of them treated with sulphonylureas) exhibited a PG value less than 4.4 mmol L(-1) at 17:00 h (P=0.0034 vs. the other timepoints). CONCLUSIONS: Glucose monitoring at 17:00 h, i.e. during the extended postlunch period, appears as a global marker of control in noninsulin-using type 2 diabetic patients both for detecting patients at risk of hypoglycaemia and for assessing the short-term quality of diabetic control.

Area Under Curve↗

Exchanging carbohydrates for monounsaturated fats in energy-restricted diets: effects on metabolic profile and other cardiovascular risk factors.

OBJECTIVE: To investigate whether improvements in cardiovascular risk factors, as observed in energy-balance conditions after exchanging carbohydrates (CHO) for monounsaturated (MUFA) fats, are also observed in energy-restricted conditions. DESIGN: Longitudinal, clinical intervention study using two types of energy-restricted diets (-30% of initial energy intake) with similar levels of saturated and polyunsaturated fats: a high CHO diet (55% of energy from CHOs, 10% from MUFAs) and a high MUFA diet (40% of energy from CHOs, 25% from MUFAs). SUBJECTS: A total of 32 overweight subjects (nine males, 23 females, BMI: 26-45 kg/m(2)). MEASUREMENTS: Body weight, serum lipids, fasting plasma insulin and phospholipid fatty acid composition of red blood cells were measured at baseline and after 8 weeks. Various oxidative status parameters (plasma lipid hydroperoxides, total plasma antioxidant capacity, plasma uric acid and vitamin E) and serum-induced smooth muscular cell (SMC) proliferation were also measured at these time points. RESULTS: Weight loss (1.1 kg/week over the first 4 weeks and 6.7 kg at week 8) was not significantly affected by the diet composition. Both diets reduced significantly total serum cholesterol, but the MUFA-rich diet showed better effects on fasting serum triacylglycerol (TG) than the CHO-rich diet: 1.18 vs 1.51 mmol/l for the MUFA-rich diet (after vs before, P<0.05) and 1.42 vs 1.62 for the CHO-rich diet. After 8 weeks, plasma vitamin E concentrations were positively associated with the oleic acid level of red blood cell phospholipids and showed opposite variations in both diets (increase with the MUFA-rich diet and decrease with the CHO-rich diet). Relative changes in SMC proliferation induced by sera were negatively associated with the ratio oleic:linoleic acid of red blood cell phospholipids and were significantly higher with the CHO-rich diet. CONCLUSIONS: The MUFA-rich diet showed better effects on serum TG than the CHO-rich diet, even with energy restriction and weight loss. The results suggest also a protective effect of oleic acid on oxidative stress and SMC proliferation, two other important cardiovascular risk factors.

Animals↗

Rare side-effects of fenofibrate.

Fibrates are widely prescribed as hypolipidemic drugs and are considered as safe. We report the case of a 69 year-old woman who probably developed a major allergic reaction following a Fenofibrate prescription (generic form) of 300 mg per day. Clinical features included asthenia, hyperthermia (40.5 degrees C) and slight muscular pain. Biological abnormalities were mildly elevated muscular enzymes and pancytopenia rapidly developed. All bacteriologic, virologic, immune and radiologic investigations were normal. Evolution was spontaneously favorable with Fenofibrate withdrawal. This is the first reported case of major fever and pancytopenia following a Fenofibrate prescription. Adverse effects of Fenofibrate are briefly reviewed and their usual favorable outcomes following drug removal are outlined.

Aged↗

[Dietary assessment in current clinical practice: how to conciliate rapidity, simplicity and reliability?].

Dietary interviews and food diaries are traditionally used for nutritional assessments. In clinical practice, these methods are time consuming, require high training, and thus remain poorly used. Furthermore, the results are frequently impaired by the underreporting phenomenon which can be due either to underrecording (failure to record what is eaten) or to undereating (volontary food restriction during the assessment period). These difficulties can be overcome by using rapid questionnaires based on 2 principles: 1) underreporting is less for proteins than for other macronutrients; 2) in developed countries, calories from proteins are relatively stable and contribute approximately to one sixth of the total daily energy intake. Estimations given by the rapid questionnaire lead to less misleading results than those provided by 7 day-food records. On the other hand, the rapid questionnaire gives an estimate of specific dietary behaviors such as nibbling, festive meals and consumption of salted entrées, sweet desserts and caloric beverages. In conclusion, helpful and simple recommendations for correcting main nutritional errors can be drawn from estimation of the above mentioned specific behaviors that correspond to a daily average of 500 kcalories.

Alcohol Drinking↗

[Insulin sensitivity and stress].

Metabolic adaptation is part of the response to stress and participate to produce a favorable state for cure. Carbohydrate metabolism is profoundly altered with an increase in basal cellular glucose uptake and utilization and in endogenous glucose production; insulin sensitivity is decreased. Glucose tolerance is altered and hyperglycemia develops. This state of hyperglycemia is most obviously directed to satisfy the increased need of the injured organs and of the inflammatory cells. The role of the cytokines in association to the stress hormones is important to these metabolic adaptations. This article reviews the main features of glucose homeostasis and the potential mechanisms leading to stress induced insulin resistance.

Blood Glucose↗