Treatment by a moisturizer of xerosis and cracks of the feet in men and women with diabetes: a randomized, double-blind, placebo-controlled study.

AIM: To evaluate a moisturizer containing urea, glycerine and petrolatum for healing deep open fissures on the feet of people with diabetes. If left untreated, open fissures, an entry point for bacteria, can lead to infection, ulceration and further complications. METHODS: This randomized, double-blind, multicentre study at 19 hospitals, general practices and diabetologists in France and Belgium included participants with diabetes and a deep open target fissure on their heel. Participants were randomized to test cream or placebo (1 : 1) for 4 weeks. Complete target fissure healing after 4 weeks (primary criterion) and 2 weeks, target fissure closure, overall fissure healing and xerosis were assessed. RESULTS: Some 167 participants were randomized (80 to test cream; 87 to placebo); all were included in the efficacy analyses. The percentage of participants with complete target fissure healing after 4 weeks was higher with test cream than placebo (46.3% vs. 33.3%): the difference did not reach statistical significance (P = 0.088). Fewer participants still had a deep open target fissure with test cream than placebo, the difference was statistically significant and clinically relevant after 2 (24.7% vs. 42.7%, P = 0.027) and 4 weeks (6.4% vs. 24.1%, P = 0.002). The difference in overall fissure healing between test cream and placebo was significant (P < 0.001) and test cream resulted in greater xerosis improvement (P < 0.001 and P = 0.002 at 2 and 4 weeks, respectively). CONCLUSION: The activity of the test cream for treating feet fissures of people with diabetes was confirmed by an improvement in open fissure healing and xerosis. The cream was well tolerated.

Skin autofluorescence and peripheral neuropathy four years later in type 1 diabetes.

OBJECTIVE: Advanced glycation end products (AGEs) are involved in diabetes complications. We aimed to investigate whether the accumulation of AGEs measured by skin autofluorescence (sAF) was associated with signs of diabetic peripheral neuropathy and to sensitivity, pain, motor and autonomic function 4 years later in patients with type 1 diabetes. METHODS: At baseline, 188 patients (age 51 years, diabetes duration 22 years) underwent skin autofluorescence measurement using the AGE Reader. Four years later, signs of diabetic peripheral neuropathy were defined as the presence of neuropathic pain and/or feet sensory loss or foot ulceration. Neurological tests were systematically performed: vibration perception threshold by neuroesthesiometry, neuropathic pain by the Douleur Neuropathique en 4 Questions score, muscle strength by dynamometry and electrochemical skin conductance. Multivariate analyses were adjusted by age, sex, height, body mass index, tobacco, HbA1c , diabetes duration, estimated glomerular filtration rate and albumin excretion rate. RESULTS: At the 4-year follow-up, 13.8% of patients had signs of diabetic peripheral neuropathy. The baseline sAF was higher in those with signs of diabetic peripheral neuropathy (2.5 ± 0.7 vs 2.1 ± 0.5 arbitrary units (AU), p < 0.0005). In the multivariate analysis, a 1 SD higher skin autofluorescence at baseline was associated with an increased risk of signs of neuropathy (OR = 2.68, p = 0.01). All of the neurological tests were significantly altered in the highest quartile of the baseline sAF (>2.4 AU) compared with the lowest quartiles after multivariate adjustment. CONCLUSION: This non-invasive measurement of skin autofluorescence may have a value for diabetic peripheral neuropathy in type 1 diabetes and a potential clinical utility for detection of diabetic peripheral neuropathy. Copyright © 2016 John Wiley & Sons, Ltd.

Is skin autofluorescence a marker of metabolic memory in pregnant women with diabetes?

AIM: To determine whether skin autofluorescence can help to detect those who have previously had abnormal glucose levels among women referred for diabetes during pregnancy. METHODS: Using an advanced glycation end product reader (AGE Reader(tm) (;) DiagnOptics BV, Groningen, the Netherlands), we measured forearm skin autofluorescence at 24-30 weeks of gestation in all women who were referred to our Nutrition Diabetology unit for diabetes during pregnancy. RESULTS: The study included 230 women (200 with gestational diabetes and 30 with pre-gestational diabetes, of whom 21 had Type 1 and nine had Type 2 diabetes) and a reference group of 22 normoglycaemic non-pregnant women. Skin autofluorescence was significantly higher in women with pre-gestational diabetes (1.97 ± 0.44 arbitary units) compared with gestational diabetes (1.77 ± 0.32 arbitary units; P = 0.003) and lower in the reference group (1.60 ± 0.32 arbitary units; P = 0.009 vs all pregnant women). Among women with gestational diabetes, 71 had a history of hyperglycaemia (i.e. gestational diabetes or macrosomia in a previous pregnancy or discovery of diabetes before 24th gestational week in the present pregnancy). These women had higher levels of skin autofluorescence (1.83 ± 0.35 arbitary units) than women with gestational diabetes without previous history of hyperglycaemia (1.73 ± 0.30 arbitary units; P = 0.04, non-significant, adjusted for age). Skin autofluorescence increased with the number of criteria present for previous hyperglycaemia (P for trend = 0.008) and was significantly associated with having two or three criteria for hyperglycaemia after adjusting for age (P = 0.02). CONCLUSIONS: Skin autofluorescence could reflect previous long-term hyperglycaemia in pregnant women, and could therefore be a marker of metabolic memory.

Self, Voices and Embodiment: A Phenomenological Analysis.

OBJECTIVE: The primary aim of this study was to examine first-person phenomenological descriptions of the relationship between the self and Auditory Verbal Hallucinations (AVHs). Complex AVHs are frequently described as entities with clear interpersonal characteristics. Strikingly, investigations of first-person (subjective) descriptions of the phenomenology of the relationship are virtually absent from the literature. METHOD: Twenty participants with psychosis and actively experiencing AVHs were recruited from the University of Illinois at Chicago. A mixed-methods design involving qualitative and quantitative components was utilized. Following a priority-sequence model of complementarity, quantitative analyses were used to test elements of emergent qualitative themes. RESULTS: The qualitative analysis identified three foundational constructs in the relationship between self and voices: 'understanding of origin,' 'distinct interpersonal identities,' and 'locus of control.' Quantitative analyses further supported identified links of these constructs. Subjects experienced their AVHs as having identities distinct from self and actively engaged with their AVHs experienced a greater sense of autonomy and control over AVHs. DISCUSSION: Given the clinical importance of AVHs and emerging strategies targeting the relationship between the hearer and voices, our findings highlight the importance of these relational constructs in improvement and innovation of clinical interventions. Our analyses also underscore the value of detailed voice assessments such as those provided by the Maastricht Interview are needed in the evaluation process. Subjects narratives shows that the relational phenomena between hearer and AVH(s) is dynamic, and can be influenced and changed through the hearers' engagement, conversation, and negotiation with their voices.

Association of advanced glycation end products and chronic kidney disease with macroangiopathy in type 2 diabetes.

AIMS: Accumulation of advanced glycation end-products (AGEs), may explain the major contribution of chronic kidney disease (CKD) to cardiovascular events in patients with type 2 diabetes (T2D) related to their impaired renal function. The aim of this study was to analyze the factors associated with AGE assessed by skin autofluorescence and their association with macroangiopathy in T2D. METHODS: We measured skin autofluorescence in patients hospitalized for T2D. Glomerular filtration rates were estimated (eGFR) by the EPI-CKD formula. Associations between skin autofluorescence, renal function and macroangiopathy were explored by multivariate analyses adjusting for diabetes duration and control. RESULTS: The 418 patients had T2D since 13.3 (SD 9.8) years on average, high mean HbA1C: 8.9%, (SD 1.8), (74 mmol/mol, (SD 15)) and often renal complications (49.4% with CKD). Their mean skin autofluorescence was 2.53 (SD 0.62) A.U. In multivariate linear regression, skin autofluorescence was significantly associated with age (+0.20 for ten more years, p<0.0001), renal insufficiency (-0.07 for less 10 mL/min/1.73 m² eGFR, p<0.0001) and smoking (+0.21, p=0.0004). Autofluorescence (p=0.01), but not CKD, was associated with macroangiopathy independent of diabetes duration and control. CONCLUSIONS: Accumulation of AGEs is independently associated with renal insufficiency and macroangiopathy in patients with T2D.

Early changes in respiratory quotient and resting energy expenditure predict later weight changes in patients treated for poorly controlled type 2 diabetes.

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.

Skin autofluorescence is associated with past glycaemic control and complications in type 1 diabetes mellitus.

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 (ß=0.15 per 10years, P<0.001) and diabetes duration (ß=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 (ß=0.10 per 1% of HbA1c, P=0.005, and ß=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.

Sight-threatening phenylketonuric encephalopathy in a young adult, reversed by diet.

Phenylketonuria (PKU) leads to severe neurological disorders in childhood, shunned by the diet. The long-term prognosis after diet diversification at adolescence is uncertain. We report a case of cortical blindness in a young patient regressive 1 month after the diet was resumed.Mr M., 25 years old, had PKU detected at birth. He maintained good serum levels of Phenylalanine (Phe) (120-300 µmol/L) during childhood and got a normal intellectual development. During adolescence he diversified his diet but maintained low meat and fish intake; Phe was ~1,200 µmol/L with no symptoms. In 2009, the patient stopped the low-Phe amino acid substitutes due to weariness. On June 27, 2011, he consulted for a decrease of visual acuity progressing for 6 months. Ophthalmologic examination found that visual acuity was 2/10 in two eyes associated to a central visual field defect. The visual evoked potentials were altered. MRI showed bilateral and symmetric occipital FLAIR hyperintensities. On admission in the Nutrional Unit on June 29, 2011, blood pressure was 120/70 mmHg, there was no other neurological abnormality. Phe was at 1,512 µmol/L, and not responsive to BH4. He was then treated with a very low-Phe diet with an amino acid substitute, and he obtained Phe between 120 and 300 µmol/L. Visual acuity was suddenly restored on August 1, 2011, with a dramatic attenuation of the MRI hyperintensities.Our observation shows that the withdrawal of the diet and substitutes exposes to serious neurological complications in adults that may reverse with a fast nutritional support.

Low physical activity in patients with type 2 diabetes: the role of obesity.

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.

Insulin glargine and risk of cancer: a cohort study in the French National Healthcare Insurance Database.

AIMS/HYPOTHESIS: Using the Echantillon Généraliste de Bénéficiaires: random 1/97 permanent sample of the French national healthcare insurance system database (EGB), we investigated whether, as previously suspected, the risk of cancer in insulin glargine (A21Gly,B31Arg,B32Arg human insulin) users is higher than in human insulin users. The investigation period was from 1 January 2003 to 30 June 2010. METHODS: We used Cox proportional hazards time-dependent models that were stratified on propensity score quartiles for use of insulin glargine vs human insulin, and adjusted for insulin, biguanide and sulfonylurea possession rates to assess the risk of cancer or death in all or incident exclusive or predominant (≥ 80% use time) users of insulin glargine compared with equivalent human insulin users. RESULTS: Only type 2 diabetic patients were studied. Exposure rates varied from 2,273 and 614 patient-years for incident exclusive users of insulin glargine or human insulin, respectively, to 3125 and 2341 patient-years for all patients predominantly using insulin glargine or human insulin, respectively. All-type cancer HRs with insulin glargine vs human insulin ranged from 0.59 (95% CI 0.28, 1.25) in incident exclusive users to 0.58 (95% CI 0.34, 1.01) in all predominant users. Cancer risk increased with exposure to insulin or sulfonylureas in these patients. Adjusted HRs for death or cancer associated with insulin glargine compared with human insulin ranged from 0.58 (95% CI 0.32, 1.06) to 0.56 (95% CI 0.36, 0.87). CONCLUSIONS/INTERPRETATION: There was no excess risk of cancer in type 2 diabetic patients on insulin glargine alone compared with those on human insulin alone. The overall risk of death or cancer in patients on insulin glargine was about half that of patients on human insulin, thereby excluding a competitive risk bias.

Painful diabetic neuropathy: diagnosis and management.

The prevalence of painful diabetic peripheral neuropathy (PDN) is about 20% in patients with type 2 diabetes and 5% in those with type 1. Patients should be systematically questioned concerning suggestive symptoms, as they are not usually volunteers. As PDN is due to small-fibre injury, the 10 g monofilament pressure test as well as the standard electrophysiological procedures may be normal. Diagnosis is based on clinical findings: type of pain (burning discomfort, electric shock-like sensation, aching coldness in the lower limbs); time of occurrence (mostly at rest and at night); and abnormal sensations (such as tingling or numbness). The DN4 questionnaire is an easy-to-use validated diagnostic tool. Three classes of drugs are of equal value in treating PDN: tricyclic antidepressants; anticonvulsants; and selective serotonin-reuptake inhibitors. These compounds may be prescribed as first-line therapy following pain assessment using a visual analogue scale. If the initial drug at its maximum tolerated dose does not lead to a decrease in pain of at least 30%, another drug class should be prescribed; if the pain is decreased by 30% but remains greater than 3/10, a drug from a different class may be given in association.

Non-invasive and quantitative assessment of sudomotor function for peripheral diabetic neuropathy evaluation.

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.

Estimation of renal function in patients with diabetes.

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.

Metabolic syndrome and cognitive decline in French elders: the Three-City Study.

OBJECTIVE: To examine associations between metabolic syndrome (MetS) and its individual components with risk of cognitive decline on specific cognitive functions. METHODS: Participants were 4,323 women and 2,764 men aged 65 and over enrolled in the longitudinal Three-City Study. Cognitive decline, defined as being in the worst quintile of the distribution of the difference between baseline score and either 2- or 4-year follow-up, was assessed by the Mini-Mental State Examination (MMSE, global cognitive function), the Isaacs Set Test (IST, verbal fluency), and the Benton Visual Retention Test (BVRT, visual working memory). MetS was defined by National Cholesterol Education Program-Adult Treatment Panel III criteria (at least 3 of 5 cardio-metabolic abnormalities: hypertension, high waist circumference, hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, hyperglycemia). Proportional hazards models were adjusted for age, gender, educational level, center, baseline cognitive score, APOE4 genotype, and other potential confounders. RESULTS: MetS at baseline was associated with an increased risk of cognitive decline on MMSE (hazard ratio [HR] = 1.22 [1.08-1.37]; p = 0.001) and BVRT (HR = 1.13 [1.01-1.26]; p = 0.03) but not on IST (HR = 1.11 [0.95-1.29]; p = 0.18). Among MetS components, hypertriglyceridemia and low HDL cholesterol were significantly associated with higher decline on MMSE; diabetes, but not elevated fasting glycemia, was significantly associated with higher decline on BVRT and IST. CONCLUSIONS: MetS as a whole and several of its components had a negative impact on global cognitive decline and specific cognitive functions in older persons.

Insulin therapy and body weight, body composition and muscular strength in patients with type 2 diabetes mellitus.

Aims. To determine the progression of body weight (BW) and body composition (BC) in patients with type 2 diabetes mellitus (T2D) on insulin therapy and the consequences on muscle strength (MS) as a reflect of free fat mass increases. Research design and methods. We analysed BC using air displacement plethysmography and MS by hand grip dynamometry in 40 T2D before and after three (M3) and six months (M6) of insulin therapy. Results. at baseline HbA1c was 9.76 +/-1.6% and BW was stable with fat mass (FM) 28 +/- 10.7 kg; and fat free mass (FFM) 52.4 +/- 11 kg; at M6, HbA1c improved to 7.56 +/- 0.8%; insulin doses tended to increase. BW gain at M6 was + 3.2 +/- 4.2 kg and with an increase of only 25% by M3; it was composed of FM, whereas FFM was unchanged. MS did not increase on insulin therapy. Conclusions. In T2D, BW gain was composed exclusively of FM with no improvement in MS.

RARgamma and TRbeta expressions are decreased in PBMC and SWAT of obese subjects in weight gain.

In order to evaluate the expression of nuclear receptors at the peripheral level in obese subjects, messenger RNA (mRNA) levels of different isoforms of retinoic acid receptor (RAR), triiodothyronine (TR), and peroxisome proliferator-activated receptor (PPAR) were determined and compared in peripheral mononuclear blood cells (PBMC) and subcutaneous white adipose tissue (SWAT). Twelve lean subjects and 68 obese subjects divided into weight gain (WG), weight-stable (WS), and weight loss (WL) groups were studied. Nuclear receptor mRNA levels were assessed in PBMC and SWAT using a quantitative real-time reverse transcription polymerase chain reaction method. mRNA levels of RARgamma were significantly lower in PBMC of obese subjects (WG -19%, WS -30%, and WL -24.7%) as in SWAT of WG (-50%). Lower mRNA levels of TRbeta were observed in PBMC and SWAT of WG (-50.7% and -28%, respectively) just as for TRalpha in PBMC of WG (-19%). In contrast, retinoid X receptors alpha (RXRalpha) and RARalpha mRNA levels were higher in PBMC of obese subjects (+53% and +54.5% in WG, +56% and +67% in WS, and +68% and +49.7% in WL, respectively), while expression of RXRalpha was lower in SWAT of WG (-24.5%). As for PPARgamma, its mRNA level was significantly higher in PBMC of WG subjects (+34%) while its expression was not modified in SWAT, contrary to the PPARgamma2 isoform which was significantly higher. These data show that in both adipose tissue and blood compartment of obese subjects, expressions of RARgamma and TRbeta were downregulated. Thus, we suggest that the expression in PBMC of obese subjects may constitute new cellular indicators of nuclear receptor retinoid and thyroid status.

Glucose flux in controlled hyperglycaemia before and after oral glucose ingestion in men with mild type 2 diabetes.

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.

Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain: 52-week data from the PREDICTIVE study in a cohort of French patients with type 1 or type 2 diabetes.

AIM: PREDICTIVE (an ongoing multinational observational study) provides an opportunity to explore the impact of insulin detemir use in routine clinical practice. Here, we report on long-term (52-week) data from a French cohort of patients (n=1772), comprising 643 with type 1 diabetes and 1129 with type 2 diabetes. METHODS: Patients were prescribed insulin detemir at their physician's discretion and assessed at various visits (baseline, 12 weeks, 26 weeks and 52 weeks). The primary endpoint was the frequency of serious adverse drug reactions, including major hypoglycaemia. Secondary endpoints included minor and nocturnal hypoglycaemia, glycaemic control (HbA(1c), fasting blood glucose and variability of fasting blood glucose) and weight change. RESULTS: The incidence of serious adverse drug reactions was low throughout the study, seen in 10 patients with type 1 diabetes (14 events, 1.6%) and seven with type 2 diabetes (seven events, 0.6%). In both type 1 and type 2 diabetes cohorts, the overall minor and nocturnal hypoglycaemic events were reduced from baseline (P<0.001), with no clinically significant changes in weight from baseline to endpoint. After 52 weeks of treatment with insulin detemir, glycaemic control improved, with reductions in: HbA(1c), by -0.6% and -0.8% in type 1 and type 2 diabetes patients, respectively; fasting blood glucose, by -1.4mmol/L and -1.9mmol/L respectively; and FBG variability, by -0.8mmol/L and -0.3mmol/L, respectively (P<0.0001 for all). CONCLUSION: Patients treated with insulin detemir in a clinical healthcare setting improved their glycaemic control with no increases in hypoglycaemia, adverse events or weight compared with baseline.

Early decrease in resting energy expenditure with bedtime insulin therapy.

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.