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Objective: Diabetic kidney disease favors diabetic foot ulcers, however we do not know whether the reverse relation exists. We investigated whether diabetic foot disease (DFD) related to an increased risk of developing renal events., Research Design and Methods: We conducted a retrospective analysis of a cohort of patients hospitalized for type 2 diabetes mellitus (T2DM) between 2009 and 2017, stratified for the risk of diabetic foot ulcer grades 0 (no risk), 1 and 2 (at risk), and 3 (DFD) according to the International Work Group on Diabetic Foot (IWGDF) classification. We highlighted new renal events (end-stage renal disease or a doubling of serum creatinine) in their medical records until December 2020. The relationship between DFD and later renal events was analyzed by multivariable Cox regression model., Results: Among 519 patients, 142 (27 %) had a DFD at baseline, and 159 (30 %) were classified as Grades 1 or 2. Thirty-six renal events occurred during the 54 ± 27 months of follow-up: 19 subjects started dialysis, 1 had a renal transplantation, and 16 had a doubling of serum creatinine: 15 each in subjects with DFD and subjects at risk, versus 6 in subjects with Grade 0 DFD (logrank: P = 0.001). Adjusted for i) age and sex; ii) hyperglycemic exposure; iii) conventional cardiovascular risk factors; iv) renal parameters: and v) new diabetic foot ulcers during follow-up, DFD (HR 2.7 to 5.9) and being at risk of DFD Grades 1-2 (HR 2.8 to 5.1) were significantly related to new renal events., Conclusion: The risk of renal events was increased in people with T2DM and DFD., Competing Interests: Declaration of competing interest Fadi Alkhami researched data and wrote the manuscript. No conflict of interest. Sébastien Rubin researched data and reviewed the manuscript. No conflict of interest. Gauthier Borderie researched data and reviewed the manuscript. No conflict of interest. Ninon Foussard researched data and reviewed the manuscript. No conflict of interest. Alice Larroumet researched data and reviewed the manuscript. No conflict of interest. Laurence Blanco researched data and reviewed the manuscript. No conflict of interest. Marie-Amélie Barbet-Massin researched data and reviewed the manuscript. No conflict of interest. Frédéric Domenge researched data and reviewed the manuscript. No conflict of interest. Kamel Mohammedi researched data and reviewed the manuscript. No conflict of interest. Vincent Rigalleau is the corresponding author, researched data, performed all the statistical analyses and wrote the manuscript. No conflict of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Cardiovascular disease is frequent in type 2 diabetes mellitus (T2DM). We investigated the relationship between skin autofluorescence (SAF) of advanced glycation end-products and later cardiovascular events (CVEs) in patients with T2DM., Research Design and Methods: We conducted a retrospective analysis of 504 patients hospitalized for uncontrolled and/or complicated T2DM between 2009 and 2017. SAF was measured using an AGE-Reader. Participants were followed up from admission to December 2020, for the onset of a CVE (myocardial infarction, stroke, revascularization procedures or cardiovascular death). The relationship between SAF and CVE was analyzed by multivariable Cox regression. Log-rank curves were used to compare CVE-free survival in patients whose SAF at admission was above versus below the whole-population median. The analysis was repeated in subjects without/with macroangiopathy (defined as myocardial infarction, stroke, peripheral revascularization) at baseline., Findings: During 54 months of follow-up, 69 (13.7%) patients had a CVE. Baseline SAF was significantly higher in patients with T2DM who later experienced a CVE (2.89 ± 0.70 arbitrary units versus 2.64 ± 0.62 in others, P = 0.002). This relationship was significant after adjusting for age, sex, conventional risk factors (diabetes duration, HbA1c, arterial hypertension, dyslipidemia, smoking, body mass index), vascular complications, C-reactive protein, and treatments for diabetes. The CVE-free survival curves differed between subjects whose SAF was above the whole-population median (log-rank: P = 0.002) and those whose SAF was above the macroangiopathy-free sub-population median (log-rank: P = 0.016)., Conclusion: SAF of advanced glycation end-products was related to a higher incidence of later CVE in patients with T2DM., Competing Interests: Declaration of competing interest No conflict of interest and no disclosure exist., (Copyright © 2024. Published by Elsevier Masson SAS.)

Aims: As diabetic retinopathy (DR) can occur even in well-controlled patients with type 2 diabetes (T2D), our study sought to determine whether it might be related to 'glucose memory' by evaluating patients' HbA1c over previous years and their skin autofluorescence (SAF)., Methods: In 334 patients with T2D and HbA1c levels≤8%, their available values of HbA1c from previous years were collected, and their SAF measured by an advanced glycation end-product (AGE) reader. Binary logistic regression analysis was then used to correlate DR with previously recorded HbA1c levels and to SAF, with adjustment for DR risk factors [age, gender, BMI, duration of diabetes, arterial hypertension, diabetic kidney disease (DKD), blood lipid levels and statin treatment]., Results: Our patients were mostly men (58.4%) aged 63±10years, with a duration of diabetes of 13±10years and HbA1c=7.1±0.7%. Of these patients, 84 (25.1%) had DR, which was associated with longer duration of diabetes and greater prevalence of DKD. A total of 605 HbA1c values from previous years were collected for time periods -4±3 months (n=255), -16±4months (n=152), -30±4months (n=93) and -62±26 months (n=105). After adjustment, the association between DR and having an HbA1c higher than the median was significant only for the oldest previous HbA1c values: OR=6.75, 95% CI: 1.90-23.90. Moreover, SAF values were higher in those with DR [2.95±0.67 arbitrary units (AU)] vs 2.65±0.65 AU with no DR (P<0.01) and were also associated with the oldest previous HbA1c values (P<0.01)., Conclusion: Our study found that 25.1% of our well-controlled T2D patients had DR, which was related to both their HbA1c levels from 5years prior to study admission and their SAF values, a marker of glucose memory., (Copyright © 2020. Published by Elsevier Masson SAS.)

Aim: While serum fructosamine may be a good marker of glucose control in pregnant women with diabetes, its relationship with macrosomia is still uncertain., Methods: In 130 hyperglycaemic women with singleton pregnancies (117 gestational diabetes mellitus, 13 pregestational diabetes), serum fructosamine and HbA1c levels were measured at 25±7 weeks of gestation. Levels in mothers of infants with and without macrosomic newborns (birth weight>4000g and/or large-for-gestational-age birth weight>90th percentile) were compared using logistic regression analysis adjusted for macrosomia risk factors., Results: These 130 pregnant women were 33±5 years old; their BMI before pregnancy was 27.7±6.9kg/m 2 , and they gained 7.5±5.1kg during the first 6 months of gestation. Glucose control was good according to HbA1c levels (5.3±0.3%; 34±2mmol/mol), yet 17/130 (13%) newborns had macrosomia: 3900±227g vs 3057±512g (P<0.001) in the others. These mothers were older and had higher parity, whereas their BMI scores before pregnancy and gestational weight gains did not differ. Fructosamine levels were also higher at 221±40μmol/L vs 192±22μmol/l (P<0.001), respectively, and remained significant even after adjusting for maternal age, BMI, parity, type of diabetes, antecedents of macrosomia and excessive gestational weight gain. By contrast, HbA1c did not differ between the two groups. In fact, nearly two-thirds (64.7%) of the mothers of macrosomic newborns had fructosamine levels>200μmol/l vs 31.9% of mothers with non-macrosomic newborns (P<0.05)., Conclusion: High fructosamine levels are associated with macrosomia in the newborns of well-controlled hyperglycaemic pregnant women., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Aim: This study looked at whether early changes in resting energy expenditure (REE) and respiratory quotient (RQ) are correlated with later weight changes in patients with type 2 diabetes (T2D) being treated with insulin or GLP-1 analogues, or diet., Methods: A total of 67 patients (age: 57 ± 9 years; BMI: 33.7 ± 5.0 kg/m(2); HbA1c: 9.9 ± 1.5%) began taking an insulin analogue at bedtime (INS, n=28; initial dose: 0.2 IU/kg) or a GLP-1 analogue (GLP-1, n=23), or only a dietary intervention (diet, n=16; restricted carbohydrates and calories). Their respiratory exchanges were monitored on days 0, 1 and 2 before breakfast., Results: Two days after starting the bedtime insulin analogue, fasting glycaemia improved (INS: -65 ± 41 mg/dL; GLP-1: -29 ± 48 mg/dL; diet: -31 ± 46 mg/dL; P<0.05), REE decreased (INS: -162 ± 241 kcal/24h; GLP-1: 0 ± 141 kcal/24h; diet: -41 ± 154 kcal/24h; P<0.05) and RQ increased (from 0.76 ± 0.04 to 0.80 ± 0.04; P<0.01), whereas only RQ decreased with diet (from 0.79 ± 0.05 to 0.76 ± 0.04; P<0.05) and remained unchanged with GLP-1 (P<0.005 for ΔRQ across treatments). Only 33 patients attended the scheduled examination three months later. HbA1c improved (INS, n=16: -1.7 ± 1.4%; GLP-1, n=12: -2.1 ± 1.4%; diet, n=5: -1.7 ± 2.8%; NS), while weight changes differed (INS: +1.5 ± 4.3 kg; GLP-1: -2.8 ± 2.8 kg; diet: -2.2 ± 2.7 kg; P<0.005). After three months, weight changes correlated with early changes in REE (r=-0.37, P<0.05) and RQ (r=+0.43, P<0.01), and remained correlated when both changes were included in a multivariate regression analysis (r=0.58, P<0.005)., Conclusion: In poorly controlled patients with T2D and two days after the introduction of a bedtime insulin analogue, REE decreased by -9% while RQ increased by +5%, pointing to a reduction of lipid oxidation. These changes were predictive of later weight gain., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

As skin autofluorescence (AF) can assess subcutaneous accumulation of fluorescent advanced glycation end-products (AGEs), this study aimed to investigate whether it was linked to glycaemic control and complications in patients with type 1 diabetes mellitus (T1DM). Using the AGE Reader™, AF was measured in T1DM patients referred to Haut-Levêque Hospital (Bordeaux, France); data on their HbA1c levels measured every 6months as far back as the last 5years were also collected. The association of AF with the patients' past glucose control, based on their latest HbA1c values, and the means of the last five and 10 HbA1c values, and with diabetic complications was also examined by linear regression analysis. The sample included 300 patients: 58% were male; the mean age was 49 (SD 17) years and the mean diabetes duration was 21 (SD 13) years. The median skin AF measurement was 2.0 [25th-75th percentiles: 1.7-2.4] arbitrary units (AU), and this was associated with age (β=0.15 per 10years, P<0.001) and diabetes duration (β=0.17 per 10years, P<0.001). After adjusting for age and estimated glomerular filtration rate (eGFR), the skin AF measurement was also related to the means of the last five and 10 HbA1c values (β=0.10 per 1% of HbA1c, P=0.005, and β=0.13 per 1% of HbA1c, P=0.001, respectively). In addition, the skin AF was associated with retinopathy (P<0.001), albuminuria (P<0.001) and decreased eGFR (P<0.001). In conclusion, the skin AF is related to the long-term glucose control and diabetic complications., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Aims: Few studies have described ambulatory activity in free-living individuals with type 2 diabetes mellitus (T2DM) using motion sensors, and none included a control group. For this reason, our study compared the physical-activity levels of outpatients with T2DM with subjects without diabetes, and examined the relationship between body mass index (BMI) and physical-activity parameters., Methods: Physical-activity levels in 70 outpatients with T2DM and 30 age-, gender- and employment-matched individuals without diabetes were measured using the SenseWear Armband™, a monitoring device validated against doubly labelled water, to assess total energy expenditure. Patients wore the SenseWear Armband™ on their right arm continuously every day for 1 week., Results: Total energy expenditure (<300 kcal/day), number of steps (<1500/day), physical-activity duration (<130 min/day) and active energy expenditure/day (<300 kcal) were all significantly lower (P<0.05) in patients with T2DM. These measures were inversely correlated with BMI, and remained significant after adjusting for age, gender, employment status and the presence of diabetes., Conclusion: Outpatients with T2DM have lower physical-activity levels than their matched controls, a characteristic that is related to their higher BMI., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Aims: Perturbation of pain sensation is considered one of the major initiating risk factors for diabetic foot ulcer. Sweat dysfunction leading to abnormal skin conditions, including dryness and fissures, can increase foot ulcer risk. The aim of this study was to evaluate Sudoscan™, a new, quick, non-invasive and quantitative method of measuring sudomotor dysfunction as a co-indicator of the severity of diabetic polyneuropathy (DPN)., Methods: A total of 142 diabetic patients (age 62±18 years, diabetes duration 13±14 years, HbA(1c) 8.9±2.5%) were measured for vibration perception threshold (VPT), using a biothesiometer, and for sudomotor dysfunction, using electrochemical sweat conductance (ESC) based on the electrochemical reaction between sweat chloride and electrodes in contact with the hands and feet. Retinopathy status was also assessed, as well as reproducibility between two ESC measurements and the effect of glycaemia levels., Results: ESC measurements in the feet of patients showed a descending trend from 66±17 μS to 43±39 μS, corresponding to an ascending trend in VPT threshold from <15 V to >25 V (P=0.001). Correlation between VPT and ESC was -0.45 (P<0.0001). Foot ESC was lower in patients with fissures, while VPT was comparable. Both VPT and foot ESC correlated with retinopathy status. Bland-Altman plots indicated good reproducibility between two measurements, and between low and high glycaemia levels., Conclusion: Sudoscan™ is a reproducible technique with results that are not influenced by blood glucose levels. Sweating status may be a quantitative indicator of the severity of polyneuropathy that may be useful for the early prevention of foot skin lesions., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Diabetes is the leading cause of chronic kidney disease (CKD), which makes estimation of renal function crucial. Serum creatinine is not an ideal marker of glomerular filtration rate (GFR), which also depends on digestive absorption, and the production of creatinine in muscle and its tubular secretion. Formulas have been devised to estimate GFR from serum creatinine but, given the wide range of GFR, proteinuria, body mass index and specific influence of glycaemia on GFR, the uncertainty of these estimations is a particular concern for patients with diabetes. The most popular recommended formulas are the simple Cockcroft-Gault equation, which is inaccurate and biased, as it calculates clearance of creatinine in proportion to body weight, and the MDRD equation, which is more accurate, but systematically underestimates normal and high GFR, being established by a statistical analysis of results from renal-insufficient patients. This underestimation explains why the MDRD equation is repeatedly found to give a poor estimation of GFR in patients with recently diagnosed diabetes and is a poor tool for reflecting GFR decline when started from normal, as well as the source of unexpected results when applied to epidemiological studies with a 60mL/min/1.73m(2) threshold as the definition of CKD. The more recent creatinine-based formula, the Mayo Clinic Quadratic (MCQ) equation, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) improve such underestimation, as both were derived from populations that included subjects with normal renal function. Determination of cystatin C is also promising, but needs standardisation., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Aims: This study aimed to determine how insufficiently suppressed endogenous glucose production vs. reduced peripheral glucose uptake contribute to postprandial hyperglycaemia in type 2 diabetes (T2D)., Methods: Eight men with T2D (age: 52+/-7 years; BMI: 26.6+/-2.3 kg/m(2); fasting glycaemia: 7.1+/-1.5 mmol/L) were compared with eight non-diabetic controls (age: 51+/-5 years; BMI: 24.6+/-2.9 kg/m(2); fasting glycaemia: 4.9+/-0.4 mmol/L). Their glucose turnover rates and hepatic glucose cycles were measured by monitoring [2H7]glucose infusion, with m+7 and m+6 enrichment, 3 h before and 4 h after the ingestion of [6,6-2H2]-labelled glucose, while maintaining glycaemia at 10 mmol/L using the pancreatic clamp technique., Results: Of the 700 mg/kg oral glucose load, 71% appeared in the systemic circulation of the T2D patients vs. 63% in the controls (NS). Endogenous glucose production and hepatic glucose cycles did not differ from normal either before or after oral glucose ingestion, while peripheral glucose uptake was reduced by 40% in the T2D group both before (P<0.01) and after (P<0.05) ingestion of oral glucose., Conclusion: When T2D patients were compared with non-diabetic subjects with similarly controlled levels of hyperglycaemia after oral glucose ingestion, they essentially differed only in peripheral glucose uptake, whereas endogenous glucose production was apparently unaltered., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Aims: In type 2 diabetes (T2D), insulin-induced weight gain may stem from a reduction in resting energy expenditure (REE). We sought to determine the early effects of insulin introduction on REE in 20 poorly controlled T2D patients., Methods: After improving the glycaemia, REE was measured on Day 0 and Day 4 during two treatment regimens: bedtime insulin (n=10, group 1); and one off (3-day) intravenous insulin infusion (n=10, group 2)., Results: Both groups were similar in age, gender, BMI, C-peptide, HbA(1c) and initial REE. By Day 4, fasting glycaemia had similarly improved in both groups: group 1: -5.3+/-2.7mmol/L vs group 2: -5.8+/-4.2 mmol/L. In group 2, the second REE was measured 12h after stopping the intravenous insulin infusion, whereas subcutaneous insulin was maintained in group 1. REE did not change in group 2 (-1.3+/-6.5%), whereas it decreased significantly in group 1 (-8.0+/-7.0%; P<0.05)., Conclusion: Bedtime insulin led to an early and specific reduction in REE.

Aims: Estimation of glomerular filtration rate (GFR) is recommended to diagnose and stratify chronic kidney disease (CKD). Can cystatin-C (cysC) assay improve the results in diabetic patients?, Methods: In 124 diabetic patients with a wide range of GFR, as determined by 51Cr-EDTA clearance (i-GFR), we estimated 'e-GFR' by: the recommended Cockcroft-Gault (CG) formula and Modification of Diet in Renal Disease (MDRD) study equation; the new Mayo Clinic quadratic (MCQ) equation; the recently proposed composite estimation including both serum creatinine and cysC; and a simplified approach dividing the MDRD by cysC if less than 1.10mg/L., Results: The highest diagnostic accuracy (receiver operating characteristic [ROC] curves) and the highest proportions of well-stratified patients were obtained by cysC and the MDRD which, however, underestimated i-GFR for patients without CKD (-17%, P<0.001). The CG overestimated GFR in KDOQI stages 1 and 2, ignored stage 5 and was the least accurate. The MCQ equation overrepresented stage 2, overestimating GFR at this stage (+23%, P<0.005). The composite estimation (54.7+/-27.0mL per minute 1.73m(2)) correlated best with i-GFR (56.1+/-35.3; r=0.90, P<0.001), and did not significantly differ from it across the entire population and within each Kidney Disease Outcome Quality Initiative (KDOQI) stage but was also biased (Bland-Altman procedure). Simply dividing the MDRD by cysC ifless than1.10mg/L produced a comparable performance and eliminated the bias., Conclusion: The recommended creatinine-based estimations of GFR need to be improved. CysC assay helps in the diagnosis and stratification of CKD and leads to better estimates of GFR in diabetic patients without any substantial increase in complexity.

Aim: To measure ketonemia in a control population of pregnant women and in a population of women with gestational diabetes (GDM). To define a normal ketonemia threshold for the controls and to determine whether or not this value could play a role in the clinical management of women with GDM., Method: Fifty-six women with a normal OGTT and 49 women with GDM were included and monitored from the 25th to the 37th week of pregnancy. Control subjects agreed to perform glycaemia and ketonemia self-monitoring 3 times a day. In addition, women with GDM were asked to measure their postprandial glycaemia. Glycaemia and ketonemia measurements were performed using Optium meters. Subjects kept a 24-hour food record twice a week., Results: The mean ketonemia was lower in the control group than in the GDM group (0.01+/-0.10 vs. 0.04+/-0.009 mmol/l; P<0.001). Ketonemia values measured before the midday meal and prior to the evening meal were lower for control subjects than for GDM patients (P=0.002 and P=0.005). Fasting ketonemia was unrelated to ketonuria in the GDM group, whereas there was a correlation in the control group (P=0.006). At least one chronic increase in ketonemia levels was observed in 47% of the women with GDM, compared with only 12% of controls. The lowest levels of evening glycaemia correlated with the highest levels of ketonemia; women with GDM reported lower food and carbohydrate intakes than controls (P<0.001)., Conclusion: This work has enabled the establishment of ketonemia reference standards in non-diabetic pregnant women. If ketonemia does indeed indicate overly restrictive dietary behavior, this parameter could be employed for monitoring adherence to the nutritional recommendations for GDM.

Two attitudes can be proposed, one consisting of making a diagnosis of neuropathy, the other seeking to grade the stage that it has reached in order to give a prognosis and above all determine the right way in which to educate the patient. In order to do this, it is important for the diagnosis to be thorough. It should be based both on listening to what the patient has to say and examining him/her. It is vital to listen to the patient because the warning signs are discreet, yet very evocative, and they will be a great help in making a positive diagnosis. They should not be confused with signs of arterial damage. They should then be interpreted by means of clinical examination and the tools that are available, i.e. essentially monitoring the osteo-tendinous reflexes and sensory signs. The sensory signs can only be studied with high-quality instruments, i.e. either a monofilament of proven technical quality and that should be used with care in line with good clinical practice recommendations, or by using a graduated tuning fork, or a neuroesthesiometer which will make it possible to obtained graduated responses, not simply binary responses of the "yes/no" variety. A whole series of scores have been put forward combining both functional and physical signs, making it possible to try to quantify the stage reached and the extent of the neuropathy. It is only by using a thorough and regularly applied routine that we can progress to establishing a better prognosis and providing a better educational service for the patient.

Aim: The National Kidney Foundation recommends stratification of renal failure into moderate (Glomerular Filtration Rate: GFR = 30-60 mL/min/1.73 m2), severe (15-30) or terminal (<15) using the Cockcroft-Gault (CG) or the Modification of Diet in Renal Disease (MDRD) equations. We studied the biases in these methods in an attempt to improve the standard CG (MCG) and devise a strategy for stratification., Methods: GFR was measured by 51Cr-EDTA clearance in 200 diabetic patients: 100 (Group 1: study of concordance) before 2003 and 100 thereafter (Group 2: validation of MCG). The CG was modified by replacing body weight by its mean value: 76., Results: In group 1, the recommended equations only correctly stratified 50 patients. The CG, not the MDRD, underestimated GFR if BMI was normal, and overestimated it in obese patients. In group 2, the MCG was well correlated with GFR and not biased by weight. Over the whole population, the MCG and MDRD were more accurate for the diagnosis of moderate and severe renal failure. The MDRD showed the lowest differences with GFR, except if GFR > 60, where the MCG performed better. All formulae overestimated low GFR, the MDRD also underestimated high GFR. The best stratification (147/200) was obtained using the MCG if creatininemia < 120 micromol/l and the MDRD if creatininemia > or =120 micromol/l., Conclusion: The CG is biased by weight, the MCG corrects this. The more accurate MDRD cannot be used in all patients as it underestimates high GFR. The best stratification was obtained using the MCG at low and the MDRD at high creatininemia.

Objective: Dietary recommendations, a pillar in the treatment of diabetes, form part of official guidelines. However, it is not known how well these recommendations are followed in the diabetic population in France. The purpose of this study was to compare the habitual diet of self-declared diabetics with non-diabetics and to evaluate whether recommendations are being followed., Methods: The intakes of several nutrients and foods of 67 self-declared diabetic patients were compared to those of 4658 non-diabetics in the SU.VI.MAX study (a primary prevention trial evaluating the impact of antioxidant supplementation on chronic disease). All patients (aged 45 to 60 years) who had completed at least five 24-hr dietary records over the first 18 months of the SU.VI.MAX study were included. We excluded patients who had not declared a diagnosis of diabetes and those with plasma fasting glucose levels over 7 mmol/l., Results: The diabetic patients who declared being diabetic reported lower carbohydrate intakes (185 +/- 10.4 vs 219 +/- 1.4 g/d for men [p=0.001], 137 +/- 9.6 vs 165 +/- 1.0 g/d for women [0.005]), with a 50% reduction in consumption of oligosaccharides. Lipid intakes were unchanged for men, but reduced for women (61 +/- 4.1 g/d vs 72 +/- 0.4 g/d [p=0.01] with a 20% reduction in saturated fatty acids. Protein consumption was higher in the diabetic than in the non-diabetic men, but comparable for the women. Energy intakes were only lower in the diabetic women (1458 +/- 81 vs 1665 +/- 9 Kcal/d for women [p=0.01]). Micronutrient intakes were similar to those of non-diabetics, but appeared to be inadequate, particularly for anti-oxidants. Diabetic men consumed more margarine and less alcohol than did the non-diabetics., Conclusion: Diabetic patients who declared being diabetic did modify their nutritional behaviour, as they reduced their carbohydrate intake (both men and women), increased their protein intake (men only), and decreased their lipid and energy intakes (women only). However, carbohydrate intakes were unbalanced and there was excess protein intake. So patients who declared being diabetic are not as non-compliant in nutrition as commonly thought; they try to modify their diet, but often inappropriately. This may be explained by the fact that dietary advice stems from different sources and may be contradictory. A diabetic education program requires standardised training of health professionals and the provision of unequivocal information to the mass media and the general public.

We present a case of emphysematous cystitis in a diabetic patient with a poor glycemic control in the context of alcoholic chronic pancreatitis. A 62-year-old woman was admitted to the emergency department after being found on floor with confusion and vomiting. The clinical examination was unremarkable except she was undernourished, agitated and presented an hepatomegaly. Urine contained 5.104 leukocytes/mm3 and culture grew Escherichia coli, 10(7) Colony Forming Unit/ml. Abdominal plain film showed gas shadows along the wall of urinary bladder. CT scan of the pelvis confirmed the presence of gas, and diffuse thickening of the urinary bladder wall. A Foley catheter was placed and the patient was treated with antibiotics for 6 weeks. She was also treated with insulin, rehydratation, vitamin B1 and B6, and pancreatic enzyme replacement. Emphysematous cystitis is defined by the presence of gas in the urinary bladder wall. It complicates urinary tract infections especially in diabetic patients but other disabled general medical conditions may be present. Because this relatively uncommon disease may present with fairly nonspecific findings, the diagnosis is often made incidentally on X-rays. However, as early diagnosis and treatment improve the outcome, a high index of suspicion for unusual presentations is warranted. Every diabetic patient with a urinary tract infection who seems to be severely ill should have an abdominal X-ray as a minimal screening tool to detect emphysematous complications.

Objective: In the present study, we measured fibrinolytic parameters, including PAI-1 antigen and activity in a group of type 2 diabetic patients in secondary oral anti-diabetic failure treated with insulin alone or with insulin plus metformin., Research Design and Methods: 12 type 2 diabetic patients in secondary oral anti-diabetic failure were randomly allocated into two groups receiving insulin alone or insulin plus metformin 1000 mg twice a day; six weeks later, the treatments were swapped over. At the end of each treatment period, blood samples were withdrawn for metabolic and fibrinolytic analysis., Results: There were no significant differences in fasting blood glucose, fructosamine or fibrinogen; LDL cholesterol, PAI-1 antigen and activity, insulin needs were reduced by the inulin plus metformin regimen (LDL cholesterol: 1.59 +/- 0.62 versus 1.28 +/- 0.5 mmol/l, PAI-1 antigen: 28.3 +/- 17.4 versus 23.9 +/- 18 ng/ml, PAI-1 activity: 23.8 +/- 9.6 versus 21.9 +/- 10 IU/ml, insulin needs: 64 +/- 18 versus 52 +/- 15 U/day (p<0.05)., Conclusion: In type 2 diabetic patients with secondary oral treatment failure, insulin alone controlled blood glucose but had no effect on the levels of PAI-1; addition of metformin improved the fibrinolytic parameters.

Objective: To compare normal and pathologic values of three different tests for screening patients at risk of foot complications: mono-filament, tuning fork and vibration threshold perception (VTP)., Methods: Two hundred and fifty consecutive patients followed-up in a diabetic clinic were screened for sensitive polyneuropathy by three different tests in three different examinations in a blind design. The 10 g mono-filament, tuning fork and Horwell neuro-esthesiometer were applied to different sites on the patients' legs and feet., Results: Thirty eight patients were identified having abnormal tests and being at risk of foot complications using the mono-filament test; 33 of them and 9 more (42 patients (33 + 9)) were identified using the tuning fork applied to the malleolus and eight more (50 patients (33 + 9 + 8)) when the tuning fork was applied to the big toe; twenty more patients (70 (33 + 9 + 8 + 20)) were identified as being at risk using the VTP at a cut-off of 25 V., Conclusion: The mono-filament test identified patient with the highest risk of foot complications, but 37 more patients were identified to be at risk from a VTP > 25 V. These patients were not detected using the mono-filament test. The VTP test provides numerical values that can help to follow the course of the risk for foot insensitivity by allowing the care team to grade the education and follow-up of the at-risk group.

The therapeutic guidelines of the seventies for type 2 diabetic patients was a monotherapy which choice was based on the BMI of the patient and a bitherapy in case of a blood glucose increase. The pathophysiologic knowledge on type 2 diabetes has moved and the disease is nowadays more complex with a loss of the beta cell mass and an insulin resistance state of the liver, muscle and adipocyte tissue associated with a defect in gastro-intestinal hormones in the postprandial state. The pathophysiologic knowledge and the existence of new therapeutic agents led us to discuss oral antidiabetic polychemotherapy at the first drug prescription. This intuitive proposition has no evidence-based arguments with prospective long-term studies that would demonstrate the benefit of such a proposition. Moreover, if nowadays we can imagine a tritherapy proposition, progress in chemistry research will conduct to a quadri- and penta-therapy with expected difficulties in therapeutic compliance of the patient.

We report the case of a 66 years old woman with a well controlled, insulin-treated, type 2 diabetes, who experienced a ten-fold increase of her daily insulin needs (from 21 to 215 U/day) after the onset of a symptomatic atrial fibrillation. Check-up for another cause of insulin resistance was negative, and insulin doses could be decreased to preceding values only after electric cardioversion. Symptomatic atrial fibrillation should be considered as a potential cause of hyperglycemia.

Peripheral diabetic neuropathy is asymptomatic as other diabetic complications. However it can have potentially serious consequences such as the development of foot ulcerations and foot amputation. Early identification of high-risk diabetic patients is needed but one must keep in mind that peripheral neuropathy always begin at the extreme distality of the lower limbs and that it may be detected at the toe level and not at the ankle level; moreover, diabetic peripheral neuropathy can affect different type of fibers and different explorations are needed for an early diagnosis. There are different tools such as monofilament, tune fork, or vibration bioesthesiometer but each has its limits and must be used with caution for being valid; some are qualitative, others are quantitative. The early detection of the high-risk patient can focus the attention of the medical and nurse team on those patients which will benefit from self foot care.

Objective: To compare a non-programmable and a programmable insulin external pump using regular insulin on glycemic stability, the risk of severe hypoglycemia and metabolic control in type 1 diabetic patients., Material and Methods: Ten type 1 diabetic patients were involved in a randomized, crossover study comparing two periods of 3 months with continuous subcutaneous insulin infusion (CSII) either with a non-programmable insulin pump or a programmable insulin pump. Comparisons were made among mean blood glucose values before and after meals, at bedtime and at 2: 00 a.m.; the risk of severe hypoglycemia assessed by the low blood glucose index (LBGI); and HbA1c., Results: Mean average blood glucose (BG) measurements were significantly lower with the programmable in comparison with the non-programmable insulin pump (respectively 157+/-78 vs. 165+/-79, p=0.034). While postprandial values for BG were not different between the two pumps, the use of the programmable pump resulted in a significant decrease in mean preprandial BG levels (140+/-68 vs. 150+/-73 mg/dl p=0.039). Conversely mean BG level was lower at 2 a.m. with the non-prgrammable pump (125+/-81 vs. 134 +/-93 mg/dl, p=0.02) but with a higher incidence of hypoglycemia. Mean LBGI was comparable with the two pumps (3.1+/-8.6 vs. 2.8+/-6.9, p=0.1). There was a 0.2% decrease in HbA1c during the programmable pump period that did not reach statistical significance (p=0.37)., Conclusions: The present study suggests that programmable external insulin pumps, although more complex and more expensive than non-programmable insulin pumps, significantly reduce fasting glycemia during the day without increasing the risk of severe hypoglycemia and are safer during the night.

Post-prandial hyperglycemia (PPHG) is an independent risk factor for the development of macrovascular complications. It is now recognized that normalizing post-prandial blood glucose is more difficult than normalizing fasting glucose. Many factors affect the post-prandial blood glucose excursion. The glycemic index of the meal depends on the nature of the ingested food and starch composition. Gastric emptying is influenced by various factors including gut hormones such as GIP and GLP1, which potentiate insulin secretion, especially in its acute first phase, now referred to as an incretin effect. They also modulate glucagon secretion. Post-prandial hyperglycemia is limited by uptake of glucose by the liver and by inhibition of endogenous glucose production in this organ. In healthy controls, hepatic glucose production is halved after a meal, whereas in glucose-intolerant individuals and type 2 diabetics this inhibition is impaired (20-30% versus 50%). The persistence of endogenous glucose production during the post-prandial phase appears to be the main culprit in the PPHG. This reduced decrease in endogenous glucose in glucose intolerant and type 2 diabetic patients depends not only on the first acute phase of insulin secretion, but above all on the non-suppressed glucagon level during the post-prandial phase. Glucagon levels fall in healthy control subjects during the post-prandial phase. Although peripheral glucose uptake by insulin-dependent tissues is altered in type 2 diabetic patients, it does not appear to be the major cause of the PPHG as there are patients with insulin resistance but without post-prandial hyperglycemia.

Progressive impairment of kidney function is one of the major problems in diabetic patients. Control of glycaemia and blood pressure is the main strategy for preventing or slowing impairment in renal function in this condition. However, contributing factors such as hyperlipidaemia and high protein intake have now been identified, and their control can be regarded as a complementary measure. The role of lipid abnormalities and hypercholesterolaemia in the pathogenesis of glomerular injury has been demonstrated in animal models, and a link between hypercholesterolaemia and diabetic nephropathy has been established in humans. To date, few intervention studies in diabetic patients have shown a slower decline in renal function. Nonetheless, in every study in which follow-up was long enough, cholesterol lowering had a beneficial effect on renal function. Although hypercholesterolaemia may not be the cause of renal injury, it represents an aggravating factor. High serum cholesterol seems to have a similar action on glomerular mesangial cells and endothelial cells. This appears to be analogous to the process of atherosclerosis, as mesangial cells possess binding sites for LDL and oxidised LDL, help recruit macrophages and secrete proliferative factors. Protein intake is another factor that can influence renal deterioration. Two meta-analyses have confirmed the beneficial effect of a low-protein diet in diabetic nephropathy, showing no adverse effects on the glycaemic control. Protein intake even seems to enhance the sensitivity of tissues and liver to insulin. Thus, there appear to be no contraindications to such diets in well-controlled diabetic patients. In short, although glycaemic and blood pressure control are still the main lines of treatment for diabetic patients, lowering blood cholesterol and restricting protein intake represent complementary measures that can help slow renal impairment.

Although insulin is a well-known cause of body weight gain, it is not clear whether it is due to the accumulation of fat or lean mass. We performed a 3 months Body-Impedance Analysis follow-up in 72 diabetic patients in a wide range of insulin indications: insulin introduction in young inaugural type 1 diabetics (n = 12), late-onset type 1 (n = 12), type 2 affected by intercurrent diseases (n = 12) or microangiopathic complications (n = 12), type 2 with failure of oral antidiabetic agents (n = 12), and insulin withdrawal in type 2 (n = 12). In type 1 patients, insulin led to the most important weight gain, but it was fat-free, with a major benefit on HbA1C. Type 2 patients affected by intercurrent diseases or microangiopathic complications had a mild, also fat-free weight gain, with a clear benefit on HbA1C. In type 2 patients with failure of oral agents, HbA1C declined less, weight gain was intermedia, but predominantly fat, mirrored by a predominant fat loss in type 2 patients whose insulin was stopped (without significant change in HbA1C). Both fat and lean mass contributed to insulin-induced body weight gain, but a significant negative relationship existed between their respective evolution in our patients (r = -0.23, p < 0.05 by linear regression analysis between delta fat mass and delta lean mass). Insulin-induced body weight gain is not univocal: insulin restaures or protects lean mass in its less controversial indications, whereas it leads to fat accumulation in type 2 patients with isolated failure of oral agents.

Two patients with non-insulin-dependent diabetes mellitus (NIDDM) and moderate chronic renal failure experienced a worsening of glycaemic control when recombinant human erythropoietin (r-HuEPO) was introduced, leading to insulin therapy. A 71-year-old woman with a 20-year history of NIDDM had presented histologically documented diabetic nephropathy for 2 years during which glucose control was stabilized by a diet and glibenclamide 10 mg. In the 6 months following introduction of r-HuEPO, hyperglycaemic symptoms developed, and HbA1C increased from 8.9% to 12.3%. During this period, no intercurrent events occurred, except epistaxis due to accelerated hypertension one month after r-HuEPO was started. A 62-year-old man had a 15-year history of NIDDM, with proliferative retinopathy, macroproteinuria and chronic renal failure for 4 years. The day after the first injection of r-HuEPO, capillary glucose level rose dramatically. In both of these cases, antihypertensive treatment was increased and insulin introduced. The role of r-HuEPO in hyperglycaemia was probable in the first case and highly probable in the second. Reports about the effects of r-HuEPO on glucose metabolism in uraemic patients are conflicting. Short- and long-term effects can differ, although long-term benefit is likely. The fact that our patients were not dialized may have been important. Clinicians should be aware that glucose control may deteriorate with r-HuEPO, requiring some uraemic NIDDM patients to undergo insulin therapy.