Association between sleep disturbances, fear of hypoglycemia and psychological well-being in adults with type 1 diabetes mellitus, data from cross-sectional VARDIA study.

AIM: To assess the relationship between sleep quality, fear of hypoglycemia, glycemic variability and psychological well-being in type 1 diabetes mellitus. METHODS: Our data were provided by the VARDIA Study, a multicentric cross-sectional study conducted between June and December 2015. Sleep characteristics were assessed by the Pittsburgh Sleep Quality Index (PSQI). Fear of hypoglycemia and psychological well-being were measured with the Hypoglycemia Fear Survey version II (HFS-II) and the Hospital Anxiety and Depression Scale (HADS), respectively. Glycemic variability (GV) was determined using the CV of three 7-point self-monitoring blood glucose profiles and the mean amplitude of glycemic excursion (MAGE). RESULTS: 315 patients were eligible for PSQI questionnaire analysis: 54% women, mean age 47 ± 15, mean diabetes duration of 24 ± 13 years, HbA1c of 7.6 ± 0.9% (60 ± 7,5mmol/mol). Average PSQI score was 6.0 ± 3.3 and 59.8% of the patients had a PSQI score > 5. HFS-II score and HADS were significantly higher among "poor" sleepers (p < 0.0001) and PSQI score was positively associated with HADS (ß = 0.22; 95% CI = 0.08;0.35). GV evaluated by CV or MAGE did not differ between "poor" and "good" sleepers (p = 0.28 and 0.54, respectively). CONCLUSIONS: Adult patients with type 1 diabetes have sleep disturbances which correlate with psychological well-being. This study suggests that psychological management can be a target to improve sleep quality in adults with type 1 diabetes mellitus.

No association between fear of hypoglycemia and blood glucose variability in type 1 diabetes: The cross-sectional VARDIA study.

AIMS: In type 1 diabetes (T1D), treatment efficacy is limited by the unpredictability of blood glucose results and glycemic variability (GV). Fear of Hypoglycemia (FOH) remains a major brake for insulin treatment optimization. We aimed to assess the association of GV with FOH in participants with T1D in an observational cross-sectional study performed in 9 French Diabetes Centres (NCT02790060). METHODS: Participants were T1D for ≥5 years, aged 18-75 years, on stable insulin therapy for ≥3 months. The coefficient of variation (CV) of blood glucose and mean amplitude of glycemic excursions (MAGE) were used to assess GV from 7-point self-monitoring of blood glucose (SMBG). FOH was assessed using the validated French version of the Hypoglycemia Fear Survey-II (HFS-II) questionnaire. RESULTS: Among a total of 570 recruited participants, 298 were suitable for analysis: 46% women, 58% on continuous subcutaneous insulin infusion [CSII], mean age 49 ±â€¯16 years, HbA1c 7.5 ±â€¯0.9%, HFS-II score 67 ±â€¯18 and 12% with recent history of severe hypoglycemia during the previous 6 months, mean CV 39.8 ±â€¯9.7% and MAGE 119 ±â€¯42 mg/dL. CV and MAGE did not significantly correlate with HFS-II score (R = -0.05;P = 0.457 and R = 0.08;P = 0.170). Participants with severe hypoglycemia in the previous 6 months had higher HFS scores. Participants with higher HFS scores presented more hypoglycemias during follow-up. CONCLUSIONS: FOH as determined using the HFS-II questionnaire was not associated with 7-point SMBG variability in participants with T1D, but was associated with a positive history of severe hypoglycemia. Higher FOH was associated with higher frequency of hypoglycemia during follow-up.

Glucose control influences glomerular filtration rate and its prediction in diabetic subjects.

OBJECTIVE: Hyperglycemia increases glomerular filtration rate (GFR), but the influence of HbA(1c) (A1C) on GFR and GFR's prediction by recommended equations remains to be determined. RESEARCH DESIGN AND METHODS: In 193 diabetic patients, we searched for an association between A1C and isotopically measured GFR (51Cr-EDTA) and their predictions by the Cockcroft and Gault formula (CG) and the modification of diet in renal disease (MDRD) equation. Their accuracy for the diagnosis of moderate (GFR <60 ml/min per 1.73 m(2)) or severe (GFR <30 ml/min per 1.73 m(2)) renal failure was compared from receiver operating characteristic (ROC) curves, before and after categorizing the patients as well (A1C 8%. The MDRD equation was more accurate and robust in diabetic patients with impaired renal function.

Cockcroft-Gault formula is biased by body weight in diabetic patients with renal impairment.

The Cockcroft-Gault (CG) formula and the modification of diet in renal disease (MDRD) equation are commonly used to estimate glomerular filtration rate (GFR), but their validity at extreme body weight is questionable. This may be significant for diabetic patients. In 122 diabetic patients with renal damage, we compared both estimates to isotopically determined GFR by correlation studies and a Bland and Altman procedure before and after categorizing the patients according to body mass index (BMI). Over the whole population, the CG overestimated GFR (CG, 51.4 +/- 23.1 mL/[min . 1.73 m2]; isotopic GFR, 44.6 +/- 21.1 mL/[min . 1.73 m2], P < .0001). The MDRD (45.2 +/- 17.9; NS vs isotopic GFR) did not overestimate GFR, but it underestimated high GFR as revealed by the Bland and Altman procedure (r = -0.26, P < .005). The CG underestimated GFR in patients with normal BMI (-14%, P < .01) and overestimated it in overweight (15%, P < .005) and obese patients (55%, P < .0001); the result and the error of the estimation were correlated with BMI. This bias did not affect the MDRD. The use of ideal instead of measured body weight improved the CG prediction, but underestimated GFR. As the BMI of the 87 type 2 diabetic subjects was higher, the CG overestimated their mean GFR by 18% (P < .001), whereas the MDRD did not. There were 25% fewer patients with delayed referral using the MDRD than with the CG. Because the estimate of GFR by the CG is proportional to body weight, it is not suited for obese diabetic patients. Although it is less easy to calculate, the MDRD is not affected by weight, and its use would avoid delay in referral to nephrologists.

Estimation of glomerular filtration rate in diabetic subjects: Cockcroft formula or modification of Diet in Renal Disease study equation?

OBJECTIVE: The Cockcroft-Gault formula is recommended for the evaluation of renal function in diabetic patients. The more recent Modification of Diet in Renal Disease (MDRD) study equation seems more accurate, but it has not been validated in diabetic patients. This study compares the two methods. RESEARCH DESIGN AND METHODS: In 160 diabetic patients, we compared the Cockcroft-Gault formula and MDRD equation estimations to glomerular filtration rates (GFRs) measured by an isotopic method ((51)Cr-EDTA) by correlation studies and a Bland-Altman procedure. Their accuracy for the diagnosis of moderately (GFR <60 ml . min(-1) . 1.73 m(-2)) or severely (GFR <30 ml . min(-1) . 1.73 m(-2)) impaired renal function were compared with receiver operating characteristic (ROC) curves. RESULTS: Both the Cockcroft-Gault formula (r = 0.74; P < 0.0001) and MDRD equation (r = 0.81; P < 0.0001) were well correlated with isotopic GFR. The Bland-Altman procedure revealed a bias for the MDRD equation, which was not the case for the Cockcroft-Gault formula. Analysis of ROC curves showed that the MDRD equation had a better maximal accuracy for the diagnosis of moderate (areas under the curve [AUCs] 0.868 for the Cockcroft-Gault formula and 0.927 for the MDRD equation; P = 0.012) and severe renal failure (AUC 0.883 for the Cockcroft-Gault formula and 0.962 for the MDRD equation; P = 0.0001). In the 87 patients with renal insufficiency, the MDRD equation estimation was better correlated with isotopic GFR (Cockcroft-Gault formula r = 0.57; the MDRD equation r = 0.78; P < 0.01), and it was not biased as evaluated by the Bland-Altman procedure. CONCLUSIONS: Although both equations have imperfections, the MDRD equation is more accurate for the diagnosis and stratification of renal failure in diabetic patients.

[Treatment of type II diabetic patients with chronic renal failure]. / Contrôle glycémique chez le patient diabétique de type 2 insuffisant rénal chronique.

Glycaemic control is a key element in the management of patients with chronic renal insufficiency, associated of course with treatment of all the other associated factors. Dietary management should not merely be wishful thinking but a reality, involving the control of body weight, the maintenance of lean body mass, the observance of a sufficient carbohydrate intake and the control of protein intake, which, always tends to be excessive in diabetics. Drug treatment with oral antidiabetics may be given without risk of iatrogenic effects: glitazone has no effect on renal metabolism but may increase water retention; glinides are insulin secretagogues without renal metabolism so there is no risk of hypoglycaemia in the event of impaired renal function; if not insulin remains an excellent alternative with, however, a change in its half-life with the elevated creatinine clearance. In all cases, the goal remains the control of glycosylated haemoglobin without iatrogenic effects.

Interest of cystatin C in screening diabetic patients for early impairment of renal function.

We compared cystatin C, creatinine, and the Cockroft formula for assessment of early renal failure, defined as a (51)Cr-EDTA clearance < 80 mL/min, in 89 diabetic patients with various degrees of renal impairment (glomerular filtration rate [GFR], 11.4 to 196.5 mL/min). The relationships between cystatin C, creatinine, and (51)Cr-EDTA clearance were linearized by plotting the reciprocals of the values, and correlation coefficients were determined. Sensitivity and specificity for the diagnosis of early renal failure were calculated from receiver operating characteristic (ROC) curves. Over the whole population, cystatin C was as well correlated with GFR (r =.74) as was creatinine (r =.67) or the Cockroft formula (r =.88). Moreover, its diagnostic accuracy was comparable to that of the 2 other parameters. Its sensitivity (86.8%) was better than that of creatinine (77.4%) for screening GFR < 80 mL/min, although the Cockroft formula was more sensitive (96.2%). The study of albuminuric diabetics (n = 63) led to similar conclusions, except for a poor sensitivity of cystatin C. In the 36 patients whose plasma creatinine was < 1 mg/dL, 10 (27.7%) had GFR < 80 mL/min. The correlation of creatinine with GFR, its diagnostic accuracy, and sensitivity were significantly lower than those of cystatin C. In this population of patients with normal creatinine levels, the correlation coefficient of cystatin C, its sensitivity, and its diagnostic accuracy were comparable to those of the Cockroft formula. A moderate reduction in GFR may be present in diabetic patients with low creatinine levels. Although Cockroft formula remains the most reliable and the less expensive tool for the evaluation of renal function, cystatin C is a more reliable criterion for screening and assessment than creatinine and represents a useful alternative to the Cockcroft-Gault formula.

Body composition of obese subjects by air displacement plethysmography: The influence of hydration.

OBJECTIVE: We investigated whether air displacement plethysmography (ADP) could detect small changes in body composition of obese subjects with alterations in hydration. RESEARCH METHODS AND PROCEDURES: Ten obese subjects (mean BMI, 39.3 +/- 2.8 kg/m2) entered the ADP chamber without and with oil (1, 2, or 4 liters), water (1, 2, or 4 liters), or mixed (1 liter oil + 1 liter water or 2 liters oil + 2 liters water) loads. Real and measured changes in body composition were compared by regression analysis and Bland-Altman procedures. RESULTS: The ADP-measured changes in volume did not differ from the real values and were strongly correlated with them (r = 0.98). In all cases, loads of differing composition and similar volume led to different values of fat, fat-free mass, and percentage fat. Water was detected as increased fat-free mass only with loads of > or =2 liters, most of the water being falsely detected as increased fat mass. The observed changes were correlated with the real ones for fat mass (r = 0.68; p < 0.0001), fat-free mass (r = 0.66; p < 0.0001), and percentage fat (r = 0.61; p < 0.0001), but fat mass changes were overestimated by approximately 1 kg, and fat-free mass changes were underestimated by approximately 1 kg. This underestimation increased with the highest water loads, as shown by the Bland-Altman plot (r = -0.27; p < 0.05). Percentage fat changes were overestimated by 0.8% (p < 0.001); the magnitude of the error was correlated with the weight of the water load (r = 0.62; p < 0.0001). DISCUSSION: ADP accurately measures changes in body volume, discriminating small changes in body composition. It overestimates changes in adiposity, as most of the increased hydration is detected as an enlarged fat mass.

The Mayo Clinic quadratic equation improves the prediction of glomerular filtration rate in diabetic subjects.

BACKGROUND: Although recommended, both the Cockcroft and Gault formula (CG) and the modification of diet in renal disease (MDRD) equation are not ideally predictive of glomerular filtration rate (GFR) in diabetic subjects; we tested whether the new Mayo Clinic Quadratic (MCQ) equation performed better. METHODS: In 200 diabetic subjects with a wide range of renal function, GFR was measured by 51Cr-EDTA clearance, and compared with the results of the three predictive equations by regression analysis and Bland and Altman procedures. The correlations with body mass index, age and albumin excretion rates were tested. The precisions (absolute difference as percentage), diagnostic accuracies [receiver operating characteristic (ROC) curves for the diagnosis of moderate and severe chronic kidney disease (CKD)], and the results of stratification according to the KDOQ classification were compared. RESULTS: The CG and MCQ overestimated mean GFR, whereas the MDRD underestimated it. Correlation coefficients and areas under the ROC curves were better for the MDRD and the MCQ as compared with the CG, which was biased by body weight (+30% overestimation in obese diabetic subjects). The absolute differences with true GFR were slightly lower for the MDRD than the MCQ, and both better than the CG. Both the MDRD and MCQ correctly stratified 65% of the subjects (CG: 55%, P<0.05). In contrast with the MDRD, the MCQ did not underestimate normal GFR, and its performance for stratification was uniformly good over a wide GFR range. CONCLUSIONS: In diabetic subjects, the MCQ has a similar diagnostic performance to the MDRD, but it does not underestimate normal GFR, which is an important advantage.

New predictive equations improve monitoring of kidney function in patients with diabetes.

OBJECTIVE: The Cockcroft-Gault and Modification of Diet in Renal Disease (MDRD) equations poorly predict glomerular filtration rate (GFR) decline in diabetic patients. We sought to discover whether new equations based on serum creatinine (the Mayo Clinic Quadratic [MCQ] or reexpressed MDRD equations) or four cystatin C-based equations (glomerular filtration rate estimated via cystatin formula [Cys-eGFR]) were less biased and better predicted GFR changes. RESEARCH DESIGN AND METHODS: In 124 diabetic patients with a large range of isotopic GFR (iGFR) (56.1 +/- 35.3 ml/min per 1.73 m2 [range 5-164]), we compared the performances of the equations before and after categorization in GFR tertiles. A total of 20 patients had a second determination 2 years later. RESULTS: The Cockcroft-Gault equation was the least precise. The MDRD equation was the most precise but the most biased according to the Bland-Altman procedure. By contrast with the MDRD and, to a lesser extent, the MCQ, three of the four Cys-eGFRs were not biased. All equations overestimated the low GFRs, whereas only the MDRD and Rule's Cys-eGFR equations underestimated the high GFRs. For the subjects studied twice, iGFR changed by -8.5 +/- 17.9 ml/min per 1.73 m2. GFR changes estimated by the Cockcroft-Gault (-4.5 +/- 6.8) and MDRD (-5.7 +/- 6.2) equations did not correlate with the isotopic changes, whereas new equation-predicted changes did: MCQ: -8.7 +/- 9.4 (r = 0.44, P < 0.05) and all four Cys-eGFRs: -6.2 +/- 7.4 to -7.3 +/- 8.4 (r = 0.60 to 0.62, all P < 0.005), such as 100/cystatin-C (r = 0.61, P < 0.005). CONCLUSIONS: The new predictive equations better estimate GFR than the Cockcroft-Gault equation. Although the MDRD equation remains the most accurate, it poorly predicts GFR decline, as it overestimates low and underestimates high GFRs. This bias is lesser with the MCQ and Cys-eGFR equations, so they better predict GFR changes.

Effects of subthalamic nucleus deep brain stimulation and levodopa on energy production rate and substrate oxidation in Parkinson's disease.

Patients with Parkinson's disease (PD) often lose weight, but after subthalamic nucleus deep brain stimulation (STN-DBS), they gain weight. We compared daily energy intake (DEI), resting energy expenditure (REE) and substrate oxidation rates (measured by indirect calorimetry) in nineteen STN-DBS-treated patients (Group S), thirteen others on pharmacologic treatment by levodopa (Group L) and eight control subjects. We also determined the acute effects of STN-DBS and levodopa on REE and substrate oxidation rates. STN-DBS treated patients gained 9.7 (SEM 7.1) kg after surgery, whereas patients on pharmacologic treatment lost 3.8 (SEM 10.0) kg since diagnosis. In STN-DBS-treated patients, REE (-16.5 %; P<0.001), lipid oxidation (-27 %; P<0.05) and protein oxidation (-46 %; P<0.05) were decreased, whereas glucose oxidation was elevated (+81 %; P<0.05) as compared to patients on pharmacologic treatment. Levodopa acutely reduced REE (-8.3 %; P<0.05) and glucose oxidation (-37 %; P<0.01) with a slight hyperglycaemic effect (after levodopa challenge: 5.6 (SEM 0.8) v. before levodopa challenge: 5.3 (SEM 0.6) mmol/l; P<0.01). Switching 'on' STN-DBS acutely reduced REE (-17.5 %; P<0.01) and lipid oxidation (-24 %; P<0.001) 30 min after starting stimulation. Fasting glycaemia was slightly but significantly reduced (5.4 (SEM 1.4) v. 5.5 (SEM 1.3) mmol/l; P<0.01). After STN-DBS, the normalization of REE and the reduction in lipid and protein oxidation contribute to the restoration of weight. As levodopa decreases glucose oxidation, the reduction in daily dose of levodopa in STN-DBS-treated patients helps prevent the effect of weight gain on glycaemia.

Parkinson's disease patients with bilateral subthalamic deep brain stimulation gain weight.

Weight, body mass index (BMI) and energy expenditure/energy intake (EE/EI) was studied in 19 Parkinson's disease (PD) patients after subthalamic deep brain stimulation (STN-DBS) versus 14 nonoperated ones. Operated patients had a significant weight gain (WG, + 9.7 +/- 7 kg) and BMI increase (+ 4.7 kg/m2). The fat mass was higher after STN-DBS. Resting EE (REE; offdrug/ON stimulation) was significantly decreased in STN-DBS patients, while their daily energy expenditure (DEI) was not significantly different. A significant correlation was found among WG, BMI increase, and pre-operative levodopa-equivalent daily dose, their reduction after STN-DBS, and the differential REE related to stimulation and the REE in the offdrug/OFF stimulation condition. In conclusion, STN-DBS in PD induces a significant WG associated with a reduction in REE without DEI adjustment.