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.

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.

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.

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.

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.

[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.

[Endemic goiter in the La Kara region (Togo). Analysis of etiologic factors]. / Etude du goitre endémique dans la région de La Kara (Togo). Analyse des facteurs etiologiques.

Among 6,035 people living in 3 villages from the area of La Kara (Togo), 984 randomized subjects were investigated to evaluate goiter prevalence and related etiologic factors. Creatinine and thiocyanates (SCN-) were measured in urine, thyroid hormones and TSH in plasma. Iodine was evaluated in urine, water, salt, soil, millet and sorgho. The amount of cassava was evaluated in food. Mean goiter prevalence was 32%, reaching to 45.9% in one village; urinary iodine remained in a low range (27.2 +/- 2.18 micrograms/g creatinine in adults, 34.3 +/- 6.7 in children--m +/- SEM) independently of the presence of endemic goiter. Urinary SCN- was increased. Low iodine values were found in food, salt, soil and water which contained few mineral elements except flour which was increased in the samples collected in one of the 3 villages. Cretinism was absent, T4, T3, TSH remained in a normal range. This study confirms a high prevalence of endemic goiter in the area of La Kara with iodine deficiency, leading to an urgent iodine supplementation.

Are pituitary and thyroid function tests useful for the monitoring of antithyroid drug treatment and the post therapeutic control of Graves' disease?

The control of Graves' disease patients treated with antithyroid drugs (ATD) involves monitoring the dose of ATD, the duration of therapy and the prediction of the long-term outcome of the disease. The sequential follow-up of free thyroid hormones and ultrasensitive TSH (USTSH) helps in monitoring of ATD therapy, except in patients complemented with thyroid hormones. The normalization of early thyroid uptake of radioiodine or pertechnetate, which seems to be closely related to circulating thyroid-stimulating immunoglobulins, confirms the remission that leads to stopping ATD therapy. The raise of plasma USTSH in a normal range within the six months following ATD withdrawal is another indicator of remission. However, the post therapeutic course of Graves' patients remains unpredictable: late relapses and hypothyroidism may occur despite the normalization of the pituitary-thyroid axis, leading to a yearly clinical control with USTSH evaluation.

Experience with long-term peritoneal insulin infusion from external pumps.

The long-term acceptability and feasibility of continuous peritoneal insulin infusion (CPII) from external pumps was evaluated in 40 insulin-dependent diabetic patients continuously treated for 1-27 months (mean 12 months). Blood glucose control was satisfactory and did not deteriorate with time (glycosylated haemoglobin 8.1 +/- 1.1%, mean +/- S.D., normal range 5.5-7.5%). Major problems included 1 episode of local peritonitis, 12 hypoglycaemic comas, 7 severe hyperglycaemic episodes, all cured without sequelae. Minor problems were frequent, mostly pump and catheter-related. Pump and catheter survival rates were 46% and 70% at one year, respectively. No peritoneal reaction was noted apart from occasional tissue growth around the catheter. This method of insulin treatment was judged satisfactory and acceptable by most of the subjects. Only one patient dropped out, after 1.5 years. These results were achieved through stringent selection of patients, intensive education with strict instructions, careful medical care, and possibly through the inherent physiological advantages of intraperitoneal insulin infusion.

Continuous peritoneal insulin infusion with portable pumps: factors affecting the operating life of the chronic catheter.

Fifty-nine chronic peritoneal catheters made of polyethylene covered with silastic were used to treat 43 IDDM patients peritoneally for 3-34 mo (mean 14 mo) with portable peristaltic pumps and U40 acidic insulin. The operative life of the catheters was determined by actuarial analysis. The mechanisms of catheter failure were determined by preremoval x-ray opacification, removal under laparoscopic examination, and electron microscopic analysis of the catheter. Factors such as age, sex, duration of diabetes, implantation and tunnelization procedures, length of the catheter, and rate of infusion were analyzed. The 50% survival rate of the catheters was 16 mo. Six catheters were irreversibly obstructed by intraluminal fibrin formation and/or extraluminal adhesions, although insulin precipitation was never encountered. Seven catheters had to be removed because of a persisting local infection. Other causes were negligible (misinsertion, irreparable break). The only factor significantly related to incidence of catheter failure was gender with respect to obstruction (1 obstruction among 24 women versus 5 among 19 men, P less than 0.03).

[HLA-DR determinations in peripheral psoriatic rheumatism]. / Les groupages HLA-DR dans le rhumatisme psoriasique périphérique.

The distribution of 7 HLA-DR antigens was compared in 25 patients with peripheral psoriatic rheumatism and in 100 healthy controls. DR7 frequency was found to be significantly increased in patients: 60%, against 27% in controls (Pc = 0.021). Peripheral psoriatic rheumatism, which is related with HLA antigens B17, B13, Bw38 and Cw6, is probably also associated with DR7.

[Personalized diet based on the assessment of caloric levels in the treatment of obesity]. / Régime personnalisé par la recherche du palier dans le traitement de l'obésité.

The diet with individual evaluation of the "caloric level" consists in a severe hypocaloric diet (400-800 calories) gradually increased by 100-200 calories every 2-3 days in order to find the level at which the weight loss ceases. This level is usually far higher than that of a conventional diet. The final diet is then obtained by decreasing the intake again by 200 to 300 calories. These diets have been studied in hospitalized then ambulatory patients. 429 patients, some of whom have been followed for over six years, have been studied. The results show that, although the initial weight loss is less important than with a conventional diet, the long-term results are satisfactory in 2/3 of the patients. Patients are distributed equally into four groups according to the degree of weight loss: -10 to -15%, -15 to -20%, -20 to -30%, greater than -30%. Maintenance of the weight loss is as good or even better than with a conventional diet, but with a more liberal program.

[Lack of correlation between frozen shoulder and HLA-B27 (author's transl)]. / Absence d'association entre HLA-B27 et la rétraction capsulaire de l'épaule.

HLA-B27 antigen is strongly correlated with ankylosing spondylitis and several other rheumatic diseases. However, data concerning frozen shoulder are contradictory. Bulgen reported an increased frequency of HLA-B27 which was not observed by Noy. We performed HLA typing of 46 French patients with frozen shoulder. We agree with Noy: frozen shoulder is not correlated with HLA-B27.