Progression of skin autofluorescence of AGEs over 4 years in patients with type 1 diabetes.

BACKGROUND: The deposit of advanced glycation end-products is involved in diabetic complications. It can be evaluated by measuring the skin autofluorescence (sAF). We searched whether sAF progressed over 4 years in type 1 diabetes and analysed its relationship with the development of nephropathy. METHODS: Two measurements of skin autofluorescence (sAF) were completed on 154 patients during years 2009 and 2013. Baseline factors associated with the progression of sAF were analysed by multivariate regression analysis. The relations among sAF progression, microalbuminuria, and impaired estimated glomerular filtration rate (eGFR) were analysed by logistic regression analysis. RESULTS: The patients were 51 ± 16 years old, with duration of diabetes of 23 ± 13 years, HbA1c: 7.7 ± 1.0%, 20.7% were treated by continuous subcutaneous insulin infusion (CSII). The sAF progressed by +18.1% over 4 years. Two interacting (P = .04) variables were associated with the later progression of sAF: mildly impaired eGFR and treatment by CSII. The patients with mildly impaired eGFR had the highest progression of sAF (+11.5% P = .01). Continuous subcutaneous insulin infusion was associated with a reduced progression of sAF in patients without kidney impairment (ß = -7.2%, P = .01). A +10% progression of sAF during the follow-up was associated with more microalbuminuria: OR = 1.45, P = .02, and more mildly impaired eGFR (<90 mL/min/1.73 m2 ): OR 1.22, P = .03 at 4 years of follow-up. CONCLUSIONS: The skin autofluorescence of advanced glycation end-products progresses in patients with type 1 diabetes, more if they have diabetic nephropathy, less if they are treated by continuous subcutaneous insulin infusion. This progression is associated with the development of nephropathy.

Energy expenditure and nutritional complications of metabolic syndrome and rheumatoid cachexia in rheumatoid arthritis: an observational study using calorimetry and actimetry.

OBJECTIVE: Altered energy expenditure may contribute to the nutritional complications of RA, metabolic syndrome (MS) and rheumatoid cachexia (RC). The main aim of this study was to evaluate whether the altered resting energy expenditure (REE) and physical activity (PA)-related energy expenditure (EE) are related to the duration of RA and inflammatory activity and nutritional complications in RA. METHODS: Among patients with well-characterized RA (duration, activity: DAS28 ESR), we measured REE by indirect calorimetry, and PA-EE by actimetry (SenseWear Armband). MS was defined according to the International Diabetes Federation criteria and RC from DXA body composition analysis. The relations between the characteristics and nutritional complications, and EE were analysed by linear regression. RESULTS: Fifty-seven patients were included [73% women, age 57 (10) years] with a wide range of disease duration: 3.8 (3.0) years, and DAS28 ESR: 3.9 (1.4). The mean REE was 1486 (256) kcal/day, associated with the DAS28 ESR (ß = +0.21, P = 0.02 after adjusting for gender and fat free mass). The prevalence of MS and RC was, respectively, 24 and 18%, and they were unrelated to each other. The patients with MS and/or RC had double the longstanding RA score (P < 0.05), twice the homeostasis model assessment of insulin resistance values (P = 0.052) and halved levels of PA (P < 0.05 for metabolic equivalent tasks (METs) and number of steps/day). Two modifiable factors were associated with the presence of MS and/or RC: a low level of PA as METs [exp(B) = 0.03, P = 0.009] and the use of glucocorticoids [exp(B) = 4.08, P = 0.046]. CONCLUSION: Low levels of PA and treatment by glucocorticoids are associated with the nutritional complications of RA, suggesting the potential for therapeutic interventions.

Skin autofluorescence predicts cardio-renal outcome in type 1 diabetes: a longitudinal study.

BACKGROUND: We aimed to analyze the relationships between skin autofluorescence (SAF) and incident macrovascular events and renal impairment after 4 years of follow-up in patients with type 1 diabetes (T1D). METHODS: Two hundred and forty-three patients (51.2 ± 16.7 years old) with T1D participated. SAF was measured by AGE-Reader-TM at inclusion. Macrovascular events (MVE), estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER) were recorded then and 4 years later. Multivariate logistic regression was used to analyze the relationships between SAF and incident MVE and renal profile 4 years later. RESULTS: Patients with incident MVE had a higher SAF (p = 0.003). SAF predicted incident MVE after adjustment for age, sex, body mass index, tobacco, diabetes duration, hypertension, HbA1c, AER, eGFR (OR 4.84 [95 % CI 1.31-17.89], p = 0.018). However, this relation was no longer significant after adjustment for history of MVE. An inverse relation was found between SAF and incident eGFR (p = 0.0001). Patients with incident eGFR <60 ml/min/1.73 m(2) had a SAF higher than patients with normal eGFR. After adjustment for the previous criteria, SAF remained associated with the risk of impaired incident eGFR (OR 7.42 [95 % CI 1.59-34.65], p = 0.018). No relation was found between SAF and increased AER 4 years later. CONCLUSIONS: SAF predicts MVE in patients with T1D, adjusted for cardiovascular risk factors but the most powerful predictive factor remains history of MVE. SAF also predicts eGFR impairment, adjusted for initial AER and renal function. SAF could be a useful non-invasive tool for estimating risk of cardiovascular or renal impairment in patients with T1D.

Resveratrol mainly stimulates the glycolytic ATP synthesis flux and not the mitochondrial one: a saturation transfer NMR study in perfused and isolated rat liver.

Our aim was to monitor the effects of resveratrol (RSV) on the respective contribution of glycolysis and oxidative phosphorylation on the unidirectional flux of ATP synthesis in whole isolated rat liver perfused with Krebs-Henseleit Buffer (KHB). The rate of tissular ATP supply was measured directly by monitoring the chemical exchange Pi toward ATP with saturation transfer (ST) (31)P nuclear magnetic resonance, a method applied for the first time for studying the effects of RSV. ST allows the measurement of the total cellular Pi→ATP chemical exchange; after specific inhibition of glycolysis with iodacetate, ST could provide the Pi→ATP flux issued from mitochondria. This latter was compared to mitochondrial ATP turn-over evaluated after chemical ischemia (CI), performed with specific inhibition (KCN) of oxidative phosphorylation, and measured by standard (31)P NMR spectroscopy. In controls (KHB alone), the apparent time constant (ks) of Pi exchange toward ATP as measured by ST was 0.48±0.04s(-1) leading to a total ATP synthesis rate of 37±3.9µmolmin(-1)g(-1). KHB+RSV perfusion increased ks (+52%; p=0.0009 vs. KHB) leading to an enhanced rate of total ATP synthesis (+52%; p=0.01 vs. KHB). When glycolysis was previously inhibited in KHB, both ks and ATP synthesis flux dramatically decreased (-87% and -86%, respectively, p<0.0001 vs. KHB without inhibition), evidencing a collapse of Pi-to-ATP exchange. However, glycolysis inhibition in KHB+RSV reduced to less extent ks (-41%, p=0.0005 vs. KHB+RSV without inhibition) and ATP synthesis flux (-18%). Using the CI method in KHB and KHB+RSV, KCN addition after glycolysis inhibition induced a rapid fall to zero of the ATP content. The mitochondrial ATP turnover R(t0) and its time constant kd mito were similar in KHB (1.18±0.19µmolmin(-1)g(-1) and 0.91±0.13min(-1)) and KHB+RSV (1.36±0.26µmolmin(-1)g(-1) and 0.77±0.18min(-1)). Since mitochondrial ATP turnover was not increased by RSV, the stimulation of Pi-to-ATP exchange by RSV mainly reflected an increase in glycolytic ATP synthesis flux. Moreover, the maintenance by RSV of a high level of Pi-to-ATP exchange after glycolysis inhibition evidenced a protective effect of the polyphenol, in agreement with our previous hypothesis of a stimulation of substrate flux throughout the glycolysis 3-carbon step.

Observation of the long-term effects of lifestyle intervention during balneotherapy in metabolic syndrome.

OBJECTIVE: Estimate the effect of lifestyle adjustment activities in patients with metabolic syndrome treated by prescribed balneotherapy. METHODS: Observational pilot cohort study with 12-month follow-up after multidimensional lifestyle training (physical, dietary, educational) during 3-week standard stay in the spa town of Eugénie-les-Bains. RESULTS: Of 145 eligible patients, 97 were included; 63 were followed and analysable. At inclusion all had ≥3 National cholesterol education program-Adult treatment panel III (NCEP-ATPIII) criteria defining metabolic syndrome, 76.2% were female, mean age was 61.2 years. At the end of follow-up (median:10.4 months, Inter-Quartile Range: [6.7;11.4]), 48 of these 63 patients (76.2%) no longer had metabolic syndrome (95%CI [65.7;86.7]). These 48 patients without metabolic syndrome at the end of follow-up represented 49.5% of the 97 included (95%CI [39.5;59.4]). CONCLUSIONS: Future studies of lifestyle interventions taking advantage of the spa environment can be expected to find least one third of patients free of metabolic syndrome at the end of 12-month follow-up in the intervention group.

Fatigue symptoms relate to systemic inflammation in patients with type 2 diabetes.

Fatigue is frequent in patients with diabetes and this symptom appears to be more prominent in type 2 rather than type 1 diabetic subjects. Chronic inflammation represents one characteristic of type 2 diabetes that may contribute to fatigue symptoms. This possibility was assessed in a sample of 20 type 2 diabetic patients relatively to a group of 20 type 1 diabetic subjects. Specific dimensions of fatigue, including general fatigue, physical fatigue, reduced activity, mental fatigue and reduced motivation, were assessed using the Multidimensional-Fatigue-Inventory (MFI). Biological assays comprised the measurement of serum inflammatory markers [high-sensitive C-reactive-protein (hsCRP), high-sensitive interleukin-6 (hsIL-6), high-sensitive tumor-necrosis-factor-α (hsTNF-α) and neopterin]. Clinical parameters including indexes of adiposity were collected. In comparison to type 1 diabetic subjects, patients with type 2 diabetes exhibited higher fatigue scores, notably in the dimensions of general fatigue, physical fatigue and reduced activity, together with greater levels of inflammatory markers that correlated with indexes of adiposity. Regression analyses controlling for diabetes duration, insulin treatment status, glycemic control and fasting status, indicated that levels of inflammatory markers, in particular hsIL-6, hsCRP and neopterin, were associated with MFI fatigue dimensions in type 2 diabetic patients. Mediation analyses revealed that adiposity did not significantly account for the relationship of inflammatory markers with fatigue scores albeit coefficient regressions decreased somewhat when this variable was controlled for in regression models. These findings indicate that systemic low-grade inflammation relates to fatigue symptoms in patients with type 2 diabetes and suggest the involvement of inflammatory processes in the pathophysiology of diabetes-related fatigue.

Resveratrol plus ethanol counteract the ethanol-induced impairment of energy metabolism: ³¹P NMR study of ATP and sn-glycerol-3-phosphate on isolated and perfused rat liver.

The effects of trans-resveratrol (RSV) combined with ethanol (EtOH) were evaluated by (31)P NMR on total ATP and sn-glycerol-3-phosphate (sn-G3P) contents measured in real time in isolated and perfused whole liver of the rat. Mitochondrial ATP turnover was assessed by using specific inhibitors of glycolytic and mitochondrial ATP supply (iodacetate and KCN, respectively). In RSV alone, the slight decrease in ATP content (-14±5% of the initial content), sn-G3P content and ATP turnover were similar to those in the Krebs-Henseleit buffer control. Compared to control, EtOH alone (14 or 70 mmol/L) induced a decrease in ATP content (-24.95±2.95% of initial content, p<0.05) and an increase in sn-G3P (+158±22%), whereas ATP turnover tended to be increased. RSV (20 µmol/L) combined with EtOH, (i) maintained ATP content near 100%, (ii) induced a 1.6-fold increase in mitochondrial ATP turnover (p=0.049 and p=0.004 vs EtOH 14 and 70 mmol/L alone, respectively) and (iii) led to an increase in sn-G3P (+49±9% and +81±6% for 14 and 70 mmol/L EtOH, respectively). These improvements were obtained only when glycolysis was efficient at the time of addition of EtOH+RSV. Glycolysis inhibition by iodacetate (IAA) evidenced an almost 21% contribution of this pathway to ATP content. RSV alone or RSV+EtOH prevented the ATP decrease induced by IAA addition (p<0.05 vs control). This is the first demonstration of the combined effects of RSV and EtOH on liver energy metabolism. RSV increased (i) the flux of substrates through ATP producing pathways (glycolysis and phosphorylative oxidation) probably via the activation of AMPkinase, and (ii) maintained the glycolysis deviation to sn-G3P linked to NADH+H⁺ re-oxidation occurring during EtOH detoxication, thus reducing the energy cost due to the latter.

Large kidneys predict poor renal outcome in subjects with diabetes and chronic kidney disease.

BACKGROUND: Renal hypertrophy occurs early in diabetic nephropathy, its later value is unknown. Do large kidneys still predict poor outcome in patients with diabetes and Chronic Kidney Disease (CKD)? METHODS: Seventy-five patients with diabetes and CKD according to a Glomerular Filtration Rate (GFR, by 51Cr-EDTA clearance) below 60 mL/min/1.73 m2 or an Albumin Excretion Rate above 30 mg/24 H, had an ultrasound imaging of the kidneys and were cooperatively followed during five years by the Diabetology and Nephrology departments of the Centre Hospitalier Universitaire de Bordeaux. RESULTS: The patients were mainly men (44/75), aged 62 +/- 13 yrs, with long-standing diabetes (duration:17 +/- 9 yrs, 55/75 type 2), and CKD: initial GFR: 56.5 (8.5-209) mL/min/1.73 m2, AER: 196 (20-2358) mg/24 H. Their mean kidney lenght (108 +/- 13 mm, 67-147) was correlated to the GFR (r = 0.23, p < 0.05). During the follow-up, 9/11 of the patients who had to start dialysis came from the half with the largest kidneys (LogRank: p < 0.05), despite a 40% higher initial isotopic GFR. Serum creatinine were initially lower (Small kidneys: 125 (79-320) micromol/L, Large: 103 (50-371), p < 0.05), but significantly increased in the "large kidneys" group at the end of the follow-up (Small kidneys: 129 (69-283) micromol/L, Large: 140 (50-952), p < 0.005 vs initial). The difference persisted in the patients with severe renal failure (KDOQI stages 4,5). CONCLUSIONS: Large kidneys still predict progression in advanced CKD complicating diabetes. In these patients, ultrasound imaging not only excludes obstructive renal disease, but also provides information on the progression of the renal disease.

[Dietary advice in type 2 diabetes]. / Diététique du diabète de type 2.

The dietary advice is a part of the global care for type 2 diabetes. First, overweight implies a caloric restriction. When poor glucose control is associated with weight gain, important errors are obvious (excess fat and sugar), providing more pills or insulin without correcting them is poorly effective, but promotes further weight gain. Normal body weight, or poor glucose control despite loss of weight, needs to reappraise the diagnosis: diabetes type, intercurrent disease. The cofactors of the "metabolic syndrom" are usually present, so saturated fat has to be reduced, while maintaining fish, fruits, vegetables and whole grain cereals. Blood pressure and dyslipidemia may need further counselling about dietary sodium, carbohydrates, cholesterol. When insulin, sulfonylurea or glinids are indicated, the dietary intake of carbohydrates has to be regular to avoid hypoglycemia.

A review of Algerian medicinal plants used in the treatment of diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants are traditionally used in Algeria to treat many disorders, including diabetes mellitus. Knowledge of the plants that are used may provide insight on their properties, for further exploration. This study reviewed all the available published and unpublished reports concerning the use of herbal medicines in the treatment of diabetes in Algeria. AIM OF THE STUDY: To describe the plants used in Algeria to treat diabetes, as reported in the literature. MATERIAL AND METHODS: Systematic review of ethnobotanical papers published in the medical literature, from literature databases (Pubmed, Web of Science), as well as Google, for English, French and Arabic -language publication, and a manual search of local libraries and bookshops, as well as the university repository of PhD and master's theses. The reference lists of the papers retrieved were also examined for further papers. RESULTS: Many plants are cited in the ethnobotanical surveys, but only very few pharmacological studies were found. In the ethnobotanical surveys, 171 plants were reported, from 58 families of which the most often cited were Asteraceae, Lamiaceae and Apiaceae. The plants with the best evidence of use and activity are: Anabasis articulata (Forssk.) Moq., Trigonella foenum-graecum L., Centaurium erythraea Rafn, Artemisia herba-alba Asso, Marrubium vulgare L., Agathophora alopecuroides (Delile) Fenzl ex Bunge, Anabasis articulata (Forssk.) Moq., Hammada elegans (Bunge) Botsch., Helianthemum kahiricum Delile, Salsola baryosma (Schult.) Dandy, Salsola vermiculata L., Olea europaea L. CONCLUSION: Traditional herbal medicines are still very much used in Algeria to control diabetes. However they are generally poorly characterized and none have been properly tested in man. There is a need for systematic evaluation of the more commonly used plants to confirm their antidiabetic activity, identify possible mechanimss of action, and recommend best use.

Butyrate ingestion improves hepatic glycogen storage in the re-fed rat.

BACKGROUND: Butyrate naturally produced by intestinal fiber fermentation is the main nutrient for colonocytes, but the metabolic effect of the fraction reaching the liver is not totally known. After glycogen hepatic depletion in the 48-hour fasting rat, we monitored the effect of (butyrate 1.90 mg + glucose 14.0 mg)/g body weight versus isocaloric (glucose 18.2 mg/g) or isoglucidic (glucose 14.0 mg/g) control force-feeding on in vivo changes in hepatic glycogen and ATP contents evaluated ex vivo by NMR in the isolated and perfused liver. RESULTS: The change in glycogen was biphasic with (i) an initial linear period where presence of butyrate in the diet increased (P = 0.05) the net synthesis rate (0.20 +/- 0.01 micromol/min.g(-1) liver wet weight, n = 15) versus glucose 14.0 mg/g only (0.16 +/- 0.01 micromol/min.g(-1) liver ww, n = 14), and (ii) a plateau of glycogen store followed by a depletion. Butyrate delayed the establishment of the equilibrium between glycogenosynthetic and glycogenolytic fluxes from the 6th to 8th hour post-feeding. The maximal glycogen content was then 97.27 +/- 10.59 micromol/g liver ww (n = 7) at the 8th hour, which was significantly higher than with the isocaloric control diet (64.34 +/- 8.49 micromol/g, n = 12, P = 0.03) and the isoglucidic control one (49.11 +/- 6.35 micromol/g liver ww, n = 6, P = 0.003). After butyrate ingestion, ATP content increased from 0.95 +/- 0.29 to a plateau of 2.14 +/- 0.23 micromol/g liver ww at the 8th hour post-feeding (n = 8) [P = 0.04 versus isoglucidic control diet (1.45 +/- 0.19 micromol/g, n = 8) but was not different from the isocaloric control diet (1.70 +/- 0.18 micromol/g, n = 12)]. CONCLUSION: The main hepatic effect of butyrate is a sparing effect on glycogen storage explained (i) by competition between butyrate and glucose oxidation, glucose being preferentially directed to glycogenosynthesis during the post-prandial state; and (ii) by a likely reduced glycogenolysis from the newly synthesized glycogen. This first demonstration of the improvement of liver glycogen storage by acute butyrate supply may be an important contribution to explaining the beneficial effects on glucose homeostasis of nutritional supply increasing butyrate amount such as fiber diets.

Consumption of Alcopops During Brain Maturation Period: Higher Impact of Fructose Than Ethanol on Brain Metabolism.

Alcopops are flavored alcoholic beverages sweetened by sodas, known to contain fructose. These drinks have the goal of democratizing alcohol among young consumers (12-17 years old) and in the past few years have been considered as fashionable amongst teenagers. Adolescence, however, is a key period for brain maturation, occurring in the prefrontal cortex and limbic system until 21 years old. Therefore, this drinking behavior has become a public health concern. Despite the extensive literature concerning the respective impacts of either fructose or ethanol on brain, the effects following joint consumption of these substrates remains unknown. Our objective was to study the early brain modifications induced by a combined diet of high fructose (20%) and moderate amount of alcohol in young rats by 13C Nuclear Magnetic Resonance (NMR) spectroscopy. Wistar rats had isocaloric pair-fed diets containing fructose (HF, 20%), ethanol (Et, 0.5 g/day/kg) or both substrates at the same time (HFEt). After 6 weeks of diet, the rats were infused with 13C-glucose and brain perchloric acid extracts were analyzed by NMR spectroscopy (1H and 13C). Surprisingly, the most important modifications of brain metabolism were observed under fructose diet. Alterations, observed after only 6 weeks of diet, show that the brain is vulnerable at the metabolic level to fructose consumption during late-adolescence throughout adulthood in rats. The main result was an increase in oxidative metabolism compared to glycolysis, which may impact lactate levels in the brain and may, at least partially, explain memory impairment in teenagers consuming alcopops.

Nutritional status in patients with diabetes and chronic kidney disease: a prospective study.

BACKGROUND: A poor nutritional status reduces the life expectancy of diabetes patients undergoing hemodialysis. OBJECTIVE: The study objective was to specify the nutritional outcome in patients with chronic kidney disease (CKD) and well-controlled diabetes. DESIGN: Forty-five diabetes patients with CKD were enrolled in a cooperative-care program designed to control glucose, blood pressure, LDL cholesterol, and the albumin excretion rate (AER). Their glomerular filtration rate (GFR), body composition, serum albumin (SA), and resting energy expenditure were assessed and compared at baseline and 2 y later. RESULTS: Thirty-five patients did not start dialysis. Their glycated hemoglobin, blood pressure, LDL cholesterol, and AER improved; their GFR declined slowly (-3.3 mL x min(-1) x 1.73 m(-2) x y(-1)). Their body mass index (BMI), lean body mass, and SA increased. The GFR decline was correlated negatively with the initial BMI (r = -0.37, P < 0.05) and positively with the initial GFR (r = 0.34, P < 0.05). Ten patients started hemodialysis: except for higher total body water (P < 0.05) and extracellular volume (P < 0.01), their initial nutritional status did not differ significantly from that of 10 patients with comparable baseline severe CKD but without dialysis. At the second evaluation, patients on hemodialysis lost lean body mass, and their SA was lower than that of the patients with severe CKD (P = 0.05); lean body mass was unchanged and SA was higher (P = 0.01) in the patients with severe CKD. No significant difference was detected for resting energy expenditure. CONCLUSIONS: Nutritional status improved in CKD patients with well-controlled diabetes without dialysis, and it deteriorated in patients who started dialysis. A high initial BMI was associated with a slower decline in GFR.

Decrease in oxidative phosphorylation yield in presence of butyrate in perfused liver isolated from fed rats.

BACKGROUND: Butyrate is the main nutrient for the colonocytes but the effect of the fraction reaching the liver is not totally known. A decrease in tissue ATP content and increase in respiration was previously demonstrated when livers were perfused with short-chain fatty acids (SCFA) such as butyrate, or octanoate. In fed rats the oxidative phosphorylation yield was determined on the whole isolated liver perfused with butyrate in comparison with acetate and octoanoate (3 mmol/L). The rate of ATP synthesis was determined in the steady state by monitoring the rate of ATP loss after inhibition of (i) cytochrome oxidase (oxidative phosphorylation) with KCN (2.5 mmol/L) and (ii) glyceraldehyde 3-phosphate dehydrogenase (glycolysis) with IAA (0.5 mmol/L). The ATP flux, estimated by 31P Nuclear Magnetic Resonance, and the measured liver respiration allowed the ATP/O ratio to be determined. RESULTS: ATP turnover was significantly lower in the presence of butyrate (0.40 +/- 0.10 micromoles/min.g, p = 0.001, n = 7) and octanoate (0.56 +/- 0.10 micromoles/min.g, p = 0.01, n = 5) than in control (1.09 +/- 0.13 micromoles/min.g, n = 7), whereas perfusion with acetate induced no significant decrease (0.76 +/- 0.10 micromoles/min.g, n = 7). Mitochondrial oxygen consumption was unchanged in the presence of acetate (1.92 +/- 0.16 vs 1.86 +/- 0.16 for control) and significantly increased in the presence of butyrate (p = 0.02) and octanoate (p = 0.0004) (2.54 +/- 0.18 and 3.04 +/- 0.15 micromoles/min.g, respectively). The oxidative phosphorylation yield (ATP/O ratio) calculated in the whole liver was significantly lower with butyrate (0.07 +/- 0.02, p = 0.0006) and octanoate (0.09 +/- 0.02, p = 0.005) than in control (0.30 +/- 0.05), whereas there was no significant change with acetate (0.20 +/- 0.02). CONCLUSION: Butyrate or octanoate decrease rather than increase the rate of ATP synthesis, resulting in a decrease in the apparent ATP/O ratio. Butyrate as a nutrient has the same effect as longer chain FA. An effect on the hepatic metabolism should be taken into account when large quantities of SCFA are directly used or obtained during therapeutic or nutritional strategies.

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.

[Microalbuminuria and urinary albumin excretion: clinical practice guidelines]. / Microalbuminurie et excrétion urinaire d'albumine: recommandations pour la pratique clinique.

Measurement of urinary albumin excretion (UAE) may be done on a morning urinary sample or on a 24 hours-urine sample. Values defining microalbuminuria are: 24 hour-urine sample: 30-300 mg/24 hours; morning urine sample: 20-200 mg/ml or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mol (women). Timed urine sample: 20-200 microg/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been shown in humans. IN DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is also a marker of CV and renal risk in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. IN NO DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of the renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence or elevation of UAE overtime is associated with deleterious outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive subjects with one or two CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome as it is in diabetic or hypertensive subjects. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is annually recommended in all subjects with microalbuminuria. MANAGEMENT: In patients with microalbuminuria, weight reduction, sodium restriction (<6 g/day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of ACEI or ARB are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non diabetic subjects, any of the five classes of antihypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or betablockers) can be used.

Nitrogen monoxide and carbon monoxide transfer interpretation: state of the art.

Just a few clinicians routinely measure the subcomponents of the lung diffusing capacity for Carbone monoxide (DLCO ). This is because the measurement of membrane and blood conductances for CO (DmCO and DbCO  = Î¸CO  × Vc , respectively) by the classic Roughton and Forster method is complicated and time consuming. In addition, it mistakenly assumes a close relationship between alveolar oxygen partial pressure (PAO2 ) and mean intracapillary oxygen partial pressure (PcapO2 ) which is the true determinant of specific conductance of haemoglobin for CO (θCO ). Besides that, the critical multistep oxygenation method along with different linear equations relating 1/θCO to PcapO2 gave highly scattered DmCO and Vc values. The Dm and Vc can also be derived from a simultaneous measurement of DLNO and DLCO with the blood resistance for NO assumed to be negligible. However, recent in vitro and in vivo experiments point towards a finite value of θNO (about 4·5 mlNO  × mlblood-1  × min-1  × mmHg-1 ). Putting together the arguments and our clinical data allows us to report here the state of the art in partitioning the CO diffusing capacity into its constitutive components, with the goal to encourage further studies examining the sensitivity of DmCO and Vc to alterations observed in parenchymal diseases.

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.