Continuous glucose monitoring in patients with type 2 diabetes: Why? When? Whom?

The overall assessment of glycaemic control in patients with type 2 diabetes should normally include the monitoring of three parameters that are usually depicted as the 'glucose triad': HbA(1c), fasting plasma glucose (FPG) and postprandial glucose (PPG) excursions. However one additional marker, the so-called 'glucose variability' might be as important as the three others since it has been demonstrated that both upward and downward glucose fluctuations are potent activators of oxidative stress. Even though many methods have been proposed for assessing glucose fluctuations, the 'mean amplitude glucose excursions' (MAGE) index remains the 'gold standard'. However MAGE estimation requires the use of continuous glucose sensors. Despite the debate on the reliability and cost of the devices that permit glucose monitoring, we suggest that interventional trials designed to evaluate the effects of glucose fluctuations on diabetic complications should benefit from the use of continuous glucose monitoring systems (CGMSs). More prosaically, the use of these technologies could be extended to current clinical care of type 2 diabetic patients especially for motivating them to accept earlier insulin treatments in case of 'oral antidiabetic drug secondary failure', and further for choosing the most appropriate insulin regimen.

Contribution of postprandial glucose to chronic hyperglycaemia: from the "glucose triad" to the trilogy of "sevens".

Even though fasting and postprandial glucose are both contributors to the overall hyperglycaemia as observed in patients with type 2 diabetes, their respective contributions are varying with the degree of diabetic control. The contribution of postprandial glucose is predominant in patients with satisfactory control of diabetes (HbAlc < 7.3%) whereas the contribution of fasting glucose increases progressively with worsening diabetes. As a consequence an overall picture of the diabetic control should normally be based on the assessment of the "glucose triad" with its three components: HbAlc which integrates the diabetic control over a 3-month period, fasting and postprandial glucose. The two later are good indicators of the glycaemic regulation over the two main physiological periods of daytime: the fasting and postprandial states. Postprandial glucose concentrations should be more particularly tested at mid-morning time since in most patients this period corresponds to the highest glucose concentrations of daytime. However postprandial measurements at 2-h after lunch provide an evaluation of the overall diabetic control since we have demonstrated that glucose concentrations < 7 mmol/L at this time point are excellent predictors of HbAlc levels < 7% (specificity 2 90%). Therefore, in order to simplify the work of health care providers the "glucose triad" concept can be translated into the trilogy of "sevens": HbA1c goals < 7% and postprandial glucose targets < 7 mmol/L 2-h after lunch, both for assessing a satisfactory diabetic control, and fasting glucose < 7 mmol/L for defining the non-diabetic state.

[Very-low-calorie-diets: is there a place for them in the management of the obese diabetic?]. / Les "very-low-calorie diets" ont-elles une place dans la prise en charge du diabétique obèse?

It is well-recognized that standard caloric restrictions (1500 kcal/day) are usually poorly effective in achieving weight losses in overweight type 2 diabetic patients. For that reason very-low-calorie-diets (VLCDs) were developed as a mean for initiating or accelerating weight reduction. Short-term studies indicate that VLCDs result generally in weight losses that are three times greater than those obtained with standard low-calorie-diets. Fasting blood glucose values are improving in parallel to weight losses and in many patients the improvement in glycemic control is better than that expected from the magnitude of weight losses. However the results are rather disappointing after several months or years of follow-up. For example it has been demonstrated that weight regain can be observed as soon as the patient is shifted to a refeeding or maintenance dietary program at the end of the VLCD period. Long-term results on glycemic control and body weight reduction are generally similar with standard low-calorie-diets and with VLCDs, the final results depending on the magnitude of weight loss whatever the prescribed diet. At short-term the VLCDs can be helpful first for initiating weight losses and second for sensitizing the patient to the potential benefits of complying to dietary measures.

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.

[Changes in dietary management of diabetic patients]. / Le changement dans la prise en charge diététique du diabétique.

In the late 1990s, diet remains the cornerstone of diabetes therapy. Dietary and nutritional recommendations should seek to reduce the hyperglycaemic state which is the main risk factor for microangiopathy. Furthermore, the prevention of macrovascular complications should lead to dietary prescriptions that combine such properties as antiatherosclerotic, antithrombotic, and antihypertensive measures and such advantages as reducing oxidative stress. The means for achieving such objectives are, first, weight-loss interventions in obese patients and, secondly, the choice of a judicious balance between carbohydrates and monounsaturated fats in all individuals. Dietary measures must achieve a compromise between their acceptability by the patient and medical requirements. For that reason, caloric restriction should be moderate, leading to progressive weight loss (-3 kg monthly), with reasonable weight targets at the end of the weight-reduction period. Compliance with dietary advice usually results in significant savings in medical costs. However, long-term maintenance of dietary measures is difficult to achieve in most individuals, except those enrolled in well-structured training programmes.

Multicentre evaluation of the DCA 2000 system for measuring glycated haemoglobin. DCA 2000 Study Group.

The recommended method for assessing long-term blood glucose control in diabetic patients is the measurement of glycated haemoglobin (Hb). The Ames DCA 2000 system for assaying glycated Hb uses an immunoassay with a monoclonal antibody specific for an aminoacid sequence within the HblAc molecule. This study compared the performance of the DCA 2000 system for HblAc measurement with that of high-performance liquid chromatography (HPLC). A total of 1.016 insulin-dependent and non-insulin-dependent diabetic patients from 5 outpatient clinics took part. The correlation coefficients between DCA 2000 and HPLC data ranged between 0.94 and 0.98, depending on site. The mean variations and 95% confidence intervals for the differences between the results for each sample were: site A 0.172 (-1.186 to 1.53), site B -0.275 (-1.317 to 0.767), site C -0.146 (-0.868 to 0.576), site D -0.088 (-0.864 to 0.688), and site E -0.251 (-1.099 to 0.597). The sensitivity of the DCA 2000 assay ranged between 80 and 94%, and the specificity between 88 and 100%, depending on site. For pooled results, the correlation coefficient assayed by the two methods was 0.95. The mean variation was -0.116 and the 95% confidence interval -1.23 to 0.998. The sensitivity of DCA 2000 was 91%, and the specificity 94%. DCA tended to underestimate HbAlc slightly as compared to HPLC. This study confirms the reliability of DCA 2000 for measuring glycated Hb. The system is easy to use and provides valuable information for the care of the diabetic patients.

Determination of protein-bound urinary gamma-carboxyglutamic acid in calcium nephrolithiasis.

Nephrocalcin is a urinary gamma-carboxyglutamic acid (Gla) containing protein that may be a physiological inhibitor of calcium oxalate nephrolithiasis. Nephrocalcin isolated from urine of stone formers seems to be abnormal in lacking Gla that is required for inhibitory activity. In order to study this hypothesis, we compared the protein-bound urinary Gla contents in 32 calcium oxalate stone formers and in 24 controls. Protein-bound Gla was resolved by reversed-phase high-performance liquid chromatography after elimination of free Gla, alkaline hydrolysis and precolumn derivatization with o-phthalaldehyde and mercaptoethanol. Protein-bound urinary Gla concentrations were similar in stone formers (0.83 +/- 0.38 mumol/l, mean +/- SD) and controls (0.81 +/- 0.27) and were less than 5% of free urinary Gla. However, excretion rates of free and protein-bound Gla (nmol/min) were higher in stone formers (P = 0.006 and P = 0.002). Positive correlations (P = 0.000) were observed between free and protein-bound Gla both in controls and in stone formers. These results do not support the hypothesis of a lacking Gla nephrocalcin in stone formers.

Landform and surface attributes for prediction of rodent burrows in the Western Usambara Mountains, Tanzania.

Previous studies suggest that rodent burrows, a proxy for rodent population are important for predicting plague risk areas. However, studies that link landform, surface attributes and rodent burrows in the Western Usambara Mountains in Tanzania are scanty. Therefore, this study was conducted in plague endemic area of the Western Usambara Mountains in northern, Tanzania, to explore the relationship between rodent burrows, and landform and surface attributes. The study was carried out in three areas corresponding to high (Lokome), medium (Lukozi) and low.(Mwangoi) frequency of reported plague cases. Data were collected from 117, 200 and 170 observation sites for Lokome, Lukozi and Mwangoi, respectively using 100 m x 200 m quadrats. Remote sensing and field surveys were used to collect data on landform and surface attributes. Rodent burrows were surveyed and quantified by counting the number of burrows in 20m x 20m grids demarcated on the main 100m x 200m quadrats. The collected data were analysed in R software using boosted regression trees (BRT) technique. Rodent burrows were found at an elevation of above 1600m in the high and medium plague frequency landscapes. No burrows were found in the low plague frequency landscape situated below 1500m. BRT analysis shows a significant relationship between landform characteristics and rodent burrows in both high and medium plague frequency landscapes. Overall, elevation and hillshade are the most important determinants of rodent burrow distribution in the studied landscapes. It is concluded that in high altitudes, specific landform attributes (hill-shade, slope, elevation) and vegetation cover- favour rodent burrowing.

Energy metabolism and substrates oxidative patterns in type 2 diabetic patients treated with sulphonylurea alone or in combination with metformin.

OBJECTIVE: To compare substrates oxidative patterns in type 2 diabetic patients treated with sulphonylurea alone or in combination with metformin. METHODS: Plasma glucose (PG), plasma insulin (PI) and substrates oxidation rates measured by indirect calorimetry were compared during a test day at 8.00 a.m. (before breakfast), 11.00 a.m. (before the lunch), 2.00 p.m. (2 h after the lunch) and at 5.00 p.m. in 56 diabetic patients treated with diet (group C, n = 14), sulphonylurea (group S, n = 14) or with a sulphonylurea-metformin combination (group SM, n = 28). RESULTS: The three groups were comparable for age, body mass index (b.m.i.), body composition and PG levels. Mean glucose oxidation (Gox) was increased since mean lipid oxidation (Lox) was decreased in group S in comparison both with group C (3.02+/-0.08 vs. 2.62+/-0.08 g/min/kg/10(3), p < 0.05; 0.53+/-0.04 vs. 0.88+/-0.09 g/min/kg/10(3), p < 0.01). Mean Lox was also decreased in group S in comparison with group SM (0.88+/-0.06 vs. 0.53+/-0.04 g/min1/kg1/10(3), p < 0.0001) whereas the difference in Gox between these latter two groups was only significant in the basal state (1.94+/-0.17 vs. 2.47+/-0.17 g/min1/kg1/10(3), p < 0.05). Mean respiratory quotient (RQ) was increased in group S (0.90+/-0.01) in comparison both with group C (0.86+/-0.01, p < 0.001) and with group SM (0.86+/-0.01, p < 0.001). Mean energy expenditure was lower in group S than in group SM (21.4+/-0.6 vs. 23.6+/-0.6 kcal/min/kg/10(3), p < 0.05). Substrates oxidative patterns, RQ values and energy expenditure were similar in group C and in group SM. CONCLUSIONS: When compared to patients treated with a sulphonylurea-metformin bitherapy, patients treated with a sulphonylurea monotherapy have a shift in their ratio of fat to carbohydrate oxidation that could make body weight loss more difficult in this latter group.

Renal handling of calcium in hypercalciuric calcium oxalate nephrolithiasis.

In order to gain further insight into the mechanisms of calcium (Ca) homeostasis in hypercalciuria, we studied 32 lithiasic patients who were divided into three groups: normocalciuric patients (NC; n = 11), patients with absorptive hypercalciuria (AH; n = 12) and patients with renal hypercalciuria (RH; n = 9). The patients were investigated on 3 occasions: during a random diet, after a Ca-restricted diet and during a Ca tolerance test. The following determinations were made: Ca intake, Ca tubular reabsorption (Ca TR), plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) levels, natriuresis and urinary protein-bound Gla. The latter was measured as a marker of urinary nephrocalcin excretion. Ca TR was decreased in hypercalciuric patients (HC). AH but not RH patients normalized their Ca TR during fasting. Plasma PTH and 1,25(OH)2D levels were similar in all the groups on the 3 occasions. Natriuresis was elevated in RH during the fasting period (p < 0.02 vs. AH). Compared with NC, protein-bound Gla urinary excretion rates (UER) were enhanced in AH after the Ca-restricted period (p < 0.02) and in RH during fasting (p < 0.02). In AH, a strong positive correlation was found between Ca TR and protein-bound Gla UER (r = 0.79, p = 0.002) following a Ca-restricted diet. In the HC group as a whole, fasting protein-bound Gla UER were correlated to plasma 1,25(OH)2D levels (r = 0.68, p < 0.001). In conclusion, the results suggest that PTH directly or indirectly through 1,25(OH)2D increases nephrocalcin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between insulin sensitivity, obesity, body fat distribution and beta-endorphinaemia in obese women.

OBJECTIVE: To study the associations of obesity (as body mass index (BMI)), of body fat distribution (as waist to hip ratio (WHR)) and of beta-endorphinaemia (beta-EP-aemia) with fasting insulin and glucose concentrations, with insulin secretion (as first phase insulin response (FPIR)) and with insulin sensitivity (SI) in obese women. DESIGN: a cross-sectional study of insulin sensitivity in obese women. SUBJECTS: 45 obese women (age: 20-70 y, BMI: 27-50). MEASUREMENTS: Frequently sampled intravenous glucose tolerance test (FSIGTT), FPIR, fasting glucose, fasting insulin, BMI, body fat topography (WHR), beta-EP-aemia, plasma ACTH. RESULTS: In univariate analysis the following positive associations were observed: fasting glucose with age and WHR, fasting insulin with BMI and WHR, beta-EP plasma concentration with WHR; SI was negatively associated with BMI, WHR and beta-EP plasma concentrations. This pattern of associations remained unaltered in multivariate analysis including age, BMI and WHR as independent variables. The contribution of beta-EP plasma concentrations to SI variability was corroborated by a stepwise multiple regression analysis: 53.8% of SI variation could be explained by BMI (30.7%), by beta-EP plasma concentrations (17.2%) and by WHR (5.9%). Finally, women were divided into two groups according to whether they had a peripheral (P-BFD, WHR < or = 0.80, n = 24) or an abdominal (A-BFD, WHR > or = 0.85, n = 16) body fat distribution. After adjustment for age and BMI, SI values were lower while beta-EP and ACTH plasma concentrations were higher in the A-BFD compared to the P-BFD group. In this latter group, 54.8% of SI variation was explained by the same variables as in the whole group. In the A-BFD group, higher WHR was associated with lower FPIR. CONCLUSIONS: 1) The major finding of this study is that, in non-diabetic obese women (especially those with a P-BFD), higher beta-EP plasma concentrations are associated with lower insulin sensitivity. This association is independent of both the magnitude of obesity and the pattern of fat distribution, although these two parameters are strong predictors of SI. 2) The major reduction in SI observed in women with A-BFD probably results from the additive effects of obesity, of elevated beta-EP plasma concentrations and of metabolic and endocrine alterations in relation with the central pattern of fat distribution.