Pierre Drouin

Reliability of Self-Monitoring of Blood Glucose by CSII Treated Patients With Type I Diabetes

The reliability of patient-generated data from self-monitoring of blood glucose (SMBG) was studied in 14 patients with type I (insulin-dependent) diabetes mellitus treated by continuous subcutaneous insulin infusion (CSII) (7 women, 7 men). The reflectance meters (Glucometer I, Ames, Elkhart, IN) used by the patients were replaced for a period of 21 days by memory-reflectance meters; patients were unaware of the memory capacity of the new meters and were instructed to continue their practice of recording the meter readings in their logbook. This study compares the data recorded in the memory-reflectance meters with those reported in the logbook. The number of SMBG measurements was different in 11 patients (differences ranging from 2 to 66). Mean glycemia was similar (8.23 ± 0.36 mM in logbook vs. 8.49 ± 0.48 mM in memory-reflectance meters), but both the M value and mean amplitude of glycemic excursions (MAGE) index were lower when calculated from logbook data (38 ± 5 vs. 48 ± 7 mM, P < .05 and 6.91 ± 0.43 vs. 7.72 ± 0.52 mM, respectively; P < .05). Overreporting (addition of phantom values in logbook) and underreporting (omission of SMBG measurements from logbook) indexes were 19 ± 7 and 12 ± 3%, respectively. Precision (percent of identical values in logbook and in memory-reflectance meters at the corresponding time) was 77 ± 6.8%. The number of SMBG measurements recorded in the memory-reflectance meter was negatively correlated with glycosylated hemoglobin [HbA1c; (r = −.85, P < .001)], whereas overreporting was positively correlated with HbA1c (r = .76, P < .01). Unreliable patients (n = 5) had slightly but not significantly higher HbA1c levels than the others (n = 9; 7.4 ± 0.5 vs. 6.2 ± 0.2% NS). Sixty-five percent of the patients had recorded values in a manner that obscured hyper- or hypoglycemia.

Decreased Erythrocyte Membrane Fluidity in Poorly Controlled IDDM: Influence of ketone bodies

OBJECTIVE To examine the factors that might alter the fluidity of erythrocyte membrane in insulin-dependent diabetes mellitus (IDDM) patients. RESEARCH DESIGN AND METHODS The subjects were 10 health men and 30 IDDM mem: 10 with good blood glucose (BG) control (HbA1c 5.88 ± 0.60% [mean ± SD]), 10 with poor BG control (HbA1C 9.48 ± 1.05%), and 10 with poor BG control and mild to moderate diabetic ketoacidosis (DKA) (HbA1C 9.12 ±2.25%, strongly positive ketonuria 3+ and elevated plasma β-hydroxybutyrate). Erythrocyte membrane fluidity was determined by fluorescence polarization using 6-(9-anthroyloxy stearic acid as fluorescent probe. RESULTS Membrane fluidity was normal in the diabetic patients with good BG control but significantly lower in the two groups of patients with poor BG control than in the healthy subjects (P < 0.01). The membrane fluidity in the poor BG control groups was also lower in the patients with DKA than in those without DKA (P < 0.01). CONCLUSIONS The factors that most influence membrane fluidity in IDDM patients appear to be hyperglycemia and ketone bodies.

Morphometric study of human hepatic cell modifications induced by fenofibrate

We have studied liver biopsies obtained in 12 hyperlipoproteinemic (HLP) patients (type II, 6; type IV, 6) treated with diet and fenofibrate, and in 15 patients (type II, 11; type IV, 4) receiving diet only. Electron microscopy of liver biopsies and the morphometric analysis according to the method of Weibel and Rohr showed mitrochondrial changes in patients treated with fenofibrate, these changes depending on the type of hyperlipoproteinemia. In type II HLP, we found a decreased volume of normal mitochondria (fenofibrate, 125.72 +/- 17.04 X 10(-3) cm3/cm3; diet only, 185.84 +/- 8.96 10(-3), P less than .05). In type IV HLP we found a decreased number of giant mitochondria (fenofibrate, 0.08 +/- 0.03 X 10(10) cm-3; diet only, 0.32 +/- 0.08 X 10(10) cm-3, P less than .05) and a decreased volume of altered mitochondria (fenofibrate, 6.00 +/- 1.44 X 10(-3) cm3/cm3; diet only, 13.61 +/- 1.17 X 10(-3), P less than .05). In contrast with the rodent studies, the present study shows no change in the number of volume of peroxisomes.

Visual Evoked Potentials in Diabetic Patients

Visual evoked potentials (VEPs) were assessed in 50 adult type I (insulin-dependent) and 19 type II (noninsulin-dependent) diabetes mellitus patients and in 54 controls. P100 wave latency was significantly longer in diabetic patients (P < .001). Twenty-eight percent of diabetic patients had P100 wave latencies above the normal range. There was no correlation between P100 latency and type or duration of diabetes mellitus, quality of metabolic control, or presence of degenerative complications. The significance of VEP abnormalities in diabetes mellitus remains speculative.

Rheological properties and membrane fluidity of red blood cells and platelets in primary hyperlipoproteinemia

Lipid fluidity of the erythrocyte membrane and intact platelets was examined in 32 male patients affected by types IIA, IIB and IV primary hyperlipoproteinemia and 15 control subjects. Lipid fluidity was determined by fluorescence polarization using two probes: DPH and TMA-DPH which are localized in different lipid areas of the cell membrane. Classical haemorheological tests were also performed including plasma viscosity, whole blood viscosity and erythrocyte aggregation. As compared to a control group, plasma viscosity and whole blood viscosity at low shear rate was significantly increased in types IIB and IV, but not in type IIA patients. In contrast, the increase in erythrocyte aggregation was significant in all HLP types. Concerning lipid fluidity, the results recorded with red cells and platelets were not significantly different for type IIA HLP compared to the control group. In contrast, erythrocyte membranes from patients with types IIB and IV HLP had a significantly higher level of fluidity in lipid regions characterized by TMA-DPH. Using DPH as a fluorescent probe, identical results were only noted in type IIB patients. Regarding intact platelets of IIB and IV patients, an increase in lipid fluidity was noted for two fluorescent probes. These findings suggest that HLP associated erythrocyte and platelet fluidity alterations are not related to hypercholesterolemia but to the triglyceride level.

Action of metformin on erythrocyte membrane fluidity in vitro and in vivo

The lipid domains of the cell membrane are believed to be one of the sites where biguanides exert their antihyperglycemic effect. We have examined the effects of metformin on the membrane fluidity of intact erythrocytes in vivo and in vitro. Membrane fluidity was measured by monitoring changes in the anisotropy of the fluorescent probe 6-antroyloxystearic acid (6-AS). The erythrocyte membranes from patients with non-insulin dependent diabetes mellitus treated with metformin were more fluid than those from non-insulin dependent diabetes mellitus patients treated by diet or healthy controls. There was no correlation between membrane fluidity and the plasma lipids or the parameters of metabolic control, suggesting that the high fluidity is an effect of metformin itself. Incubation of erythrocytes from healthy controls and diabetic patients treated by diet or glibenclamide with metformin in vitro confirmed that metformin increases the fluidity of erythrocyte membranes. In vitro metformin did not alter the fluidity of membranes from diabetic patients treated with metformin, perhaps because the basal high fluidity due to their in vivo interaction with plasma metformin could be increased no further. Since insulin appears to be required for the antihyperglycemic effect of metformin, the effect of insulin on membrane fluidity was also evaluated. Insulin generally had a small fluidizing effect on erythrocytes in vitro. The fluidizing action of both insulin and metformin could represent a membrane event common to the hormone and drug leading to additive or synergistic effects in vivo.

Impaired autonomic control of heart rate and blood pressure in obesity: role of age and of insulin-resistance.

The objectives of this study were to investigate cardiac and peripheral autonomic nervous system changes in normotensive overweight or obese subjects and the possible relation between these changes and insulin resistance independent of age. The authors used spectral analysis to measure simultaneously the short-term variability of heart rate (HR) and blood pressure (BP) using a Finapres device, in 67 normotensive over-weight or obese patients (age 37±12 y, body mass index [BMI]=37±9 kg/m2) and 45 never-obese subjects (controls; age 41±13 y, BMI 22±2 kg/m2). The spectral density was determined in three situations: subjects in the supine position, spontaneously breathing; subjects in the supine with controlled breathing; and subjects standing. The insulin sensitivity of overweight and obese subjects was determined from homeostatic model assessment (HOMA). The variability of normalized low-frequency (LF) spectral analysis of both HR and BP was lower in overweight or obese subjects than in controls, in the supine and standing positions (p<0.01). Normalized LF spectral analysis was negatively correlated to BMI independent of age, whatever the position. Homeostatic model assessment values were negatively correlated to the normalized LF spectral of HR, systolic BP and diastolic BP, in the standing position independent of BMI and age (p<0.05). Normalized high frequency (HF) of HR during controlled breathing decreased with age but not with BMI. In normotensive overweight or obese subjects, changes in sympathetic nervous system modulation are strongly correlated to insulin resistance. Decreased HR and BP variability could partly account for the higher cardiovascular risk and incidence of sudden death in obese persons.

The Prevalence of Retinopathy Is Similar in Diabetes Mellitus Secondary to Chronic Pancreatitis With or Without Pancreatectomy and in Idiopathic Diabetes Mellitus

In a retrospective study, we compared the prevalence of retinopathy in two groups of 88 diabetic patients (84 men, 4 women) with either diabetes mellitus secondary to chronic pancreatitis (CP-DM group) or idiopathic diabetes mellitus (I-DM group). The patients of these two groups were pair-matched according to age (48.7 ± 1.1 versus 48.8 ± 1.0 yr in CP-DM and I-DM groups, respectively; mean ± SEM), sex, duration of diabetes (7.96 ± 0.56 versus 8.08 ± 0.8 yr) and therapy (80 on insulin and 8 on oral hypoglycemic agents in each group). Retinopathy was assessed by bilateral ophthalmoscopic examination of the fundus after pupillary dilation in all 176 patients and by fluorescein angiography in 47 patients with CP-DM and 35 patients with I-DM. Forty-one percent of patients in the CP-DM group and 45.5% of patients in the I-DM group had diabetic retinopathy (P > 0.5). In each group, patients with retinopathy were older than patients without retinopathy (51.6 ± 1.3 versus 46.7 ± 1.8 yr in the CP-DM group, P < 0.01, and 52.1 ± 1.5 versus 46.0 ± 1.2 yr in the ID-M group, P < 0.01). They had diabetes of longer duration (10.9 ± 1.0 versus 5.9 ± 0.6 yr in the CP-DM group, P < 0.001, and 10.5 ± 1.0 versus 6.0 ± 0.6 yr in the ID-M group, P < 0.001). The prevalence of retinopathy increased parallel to the duration of diabetes in a similar way in both groups. The part played in the pathogenesis of retinopathy by the following factors is also discussed: blood glucose control, arterial blood pressure, plasma total cholesterol and triglyceride levels, and family history of diabetes mellitus. Our data suggest that patients with diabetes secondary to chronic pancreatitis are at similar risks of retinopathy.

Improved Visual Evoked Potential Latencies In Poorly Controlled Diabetic Patients After Short-Term Strict Metabolic Control

OBJECTIVE To determine whether short-term strict control of blood glucose can improve abnormal visual evoked potentials (VEPs) in poorly controlled diabetic patients with no overt diabetic complications. RESEARCH DESIGN AND METHODS VEPs (P100 wave latencies) were recorded in 12 poorly controlled diabetic patients (7 with insulin-dependent diabetes mellitus and 5 with non-insulin-dependent diabetes mellitus) before and after at least 3 days of near normoglycemia obtained by continuous subcutaneous insulin infusion (CSII). Exclusion criteria were overt diabetic neuropathy or retinopathy. The control subjects were 12 healthy subjects matched for age and sex. Fifty-two other subjects formed a reference control population. The intra-individual coefficient of variation for P100 latency was < 3%. RESULTS The P100 latencies were longer in diabetic patients than in control subjects (means of both eyes ± SD: 116.8 ± 10.1 vs. 106.2 ± 4.5 ms, P < 0.01), and 4 of the 12 diabetic patients had abnormal VEPs. After 3 days of close blood glucose control (mean blood glucose profile fell from 13.7 ± 2.2 mmol/l to 6.8 ± 1.2 mmol/l, P < 0.01), the mean P100 latencies were significantly shorter (112.5 ± 7.6 ms, P < 0.01) but were still significantly longer than control values. The longer the initial P100 latency, the greater the decrease after CSII. There was no correlation between the fall in blood glucose and improvement in VEPs. CONCLUSIONS Short-term blood glucose normalization is associated with improved P100 wave latency in uncomplicated diabetic patients. These data suggest that abnormal VEPs are partly reversible and include functional disturbances related to glucose metabolism.

Circadian and Ultradian Rhythms in Blood Glucose and Plasma Insulin of Healthy Adults

The circadian and ultradian variations of blood glucose and plasma insulin have been characterized individually and as a group phenomenon in five healthy young adults studied while adhering as closely as possible to their usual routine of sleep, activity, meal content and timing. Three complementary methods were used to analyze the data: displaying raw data as a function of time; cosinor method according to Nelson and Halberg; and time series analyses as proposed by De Prins and Malbecq. The subjects were studied in the laboratory and their life routine were controlled, but very close to that of their habitual routine. They had mainly ultradian rhythms of blood glucose (mainly about 6 hr) and circadian rhythms of immunoreactive insulin (I.R.I.). Blood glucose ultradian rhythms seem to be mainly but not exclusively mealtime dependent, while I.R.I. circadian rhythms appear to be primarily endogenous in origin. Therefore, the role played by insulin in the control of blood glucose levels seems to be programmed on a circadian basis rather than by a time independent feedback phenomenon as postulated by the conventional homeostatic hypothesis. The advantage of this chronophysiologic approach is to consider circadian rhythms of both I.R.I. and insulin effectiveness as an adaptive phenomenon able to maintain blood sugar changes in the ultradian domain of rhythms.