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The authors discuss a report about the risk factors for neonatal hypoglycaemia in 767 women with gestational diabetes mellitus (GDM). Topics mentioned include intrauterine epigenetic modifications driven by early hyperglycaemia, an increase in advanced glycation end-products from no diabetes to early and regular GDM, and attributes of mothers with gestational diabetes according to the presence of neonatal hypoglycaemia in their newborn.

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. [ABSTRACT FROM AUTHOR]

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™; 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. [ABSTRACT FROM AUTHOR]

Aims Several reports have suggested a relationship between male sex and albuminuria in Type 2 diabetes, but impact on renal function decline has not been established. Our aim was to describe the influence of sex on renal function decline in Type 2 diabetes. Methods SURDIAGENE, an inception cohort, consisted in 1470 people with Type 2 diabetes. Patients without renal replacement therapy and with ≥ 3 serum creatinine determinations during follow-up prior to end-stage renal disease were included in the study. Estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Primary outcome was steep estimated glomerular filtration rate ( eGFR) decline, defined as a yearly slope value lower than -3.5 ml min−1 1.73 m−2. Secondary outcomes were estimated glomerular filtration rate trajectories according to sex and occurrence of end-stage renal disease. Results A total of 22 914 serum creatinine determinations were considered in 1146 participants (60% men), aged 65 ± 11 years, with a median follow-up duration of 5.7 years (range 0.1-10.2). Median yearly estimated glomerular filtration rate slope was -1.31 ml min−1 1.73 m−2 in women and -1.77 ml min−1 1.73 m−2 in men ( P < 0.001). Men were more likely than women to develop end-stage renal disease (22 men vs. 7 women; Plog-rank = 0.03). Male sex was an independent risk factor of steep estimated glomerular filtration rate decline [adjusted odds ratio = 1.33 (1.02-1.76), P = 0.04] after adjustment for age, time from diagnosis of Type 2 diabetes, glycated haemoglobin, systolic blood pressure and urinary albumin:creatinine ratio. A multivariable linear mixed-effects model showed a significant difference of estimated glomerular filtration rate trajectories between men and women ( P < 0.001). Conclusion Male sex is an important independent factor associated with renal function decline in Type 2 diabetes. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated diabetic neuropathy in elderly people with type 1 diabetes that use continuous subcutaneous insulin infusion (CSII). Topics explored include the comparison of clinical outcomes observed in research participants that use either CSII or multiple daily insulin injections, the age, gender, and duration of diabetes of subjects, and the concerns raised over the criteria for the diagnosis of diabetic neuropathy.

The authors discuss a report on the use of continuous subcutaneous insulin infusion in most pregnant women with type 1 diabetes. Topics mentioned include the link of smoke with less gestational weight gain and fewer large-for-gestational age babies, the metabolic actions from infused versus injected insulin after bolus infusion, and changes in the mode of insulin delivery or pharmacological approaches using pramlintide or acarbose.

AIMS: To identify factors associated with insulin requirement in Type 2 diabetic patients, and to examine the significance of a normal plasma triglyceride level. METHODS: One hundred and three poorly controlled (HbA1c = 9.4 +/- 1.9%) Type 2 diabetic patients initially not treated with insulin were followed up for 5 years. Insulin was administered if HbA1c > 8% despite maximal oral anti-diabetic treatment and bodyweight control. Variables were compared between insulin requiring and non-insulin-treated patients using unpaired t-tests. The outcomes of initially normotriglyceridaemic (< 1.7 mmol/l) and hypertriglyceridaemic patients were compared using unpaired t-tests, and a survival analysis (Cox proportional hazards model). RESULTS: Sixty-three patients were transferred to insulin. They were 5 years older (P = 0.004), with a 3-year longer duration of their diabetes (P = 0.03), a 1.2% higher HbA1c (P = 0.002), and 50% lower triglyceride levels (P = 0.02) than the others. The survival analysis showed that a long duration of diabetes, a high HbA1c, and a normal triglyceride level were associated with the need for insulin; the effect of normotriglyceridaemia was significant in the most poorly controlled (HbA1c > 9.5%) patients (relative risk: 2.35, 95% confidence interval: 1.16-5.52, P = 0.016). The 46 normotriglyceridaemic patients were leaner (P = 0.0004) and had lower C-peptide levels (P = 0.0008) than the others. Despite similar diabetes duration and HBA1c, more were transferred to insulin (normotriglyceridaemic: 71%, hypertriglyceridaemic: 52%, P = 0.03). CONCLUSION: A normal triglyceride level is associated with a need for insulin in poorly controlled Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Presents letters to the editor referencing articles and topics discussed in previous issues. "Nutritional Factors and Diabetic Foot: A Role for Vitamin E?"; "Genotype in Human CD36 Deficiency and Diabetes Mellitus," which focused on the association between CD36 deficiency and insulin resistance; "Post-Prandial Administration of Insulin Lispro with a High Fat Meal Minimizes Risk of Hypoglycemia in Type 1 Diabetes" which discusses the absorption of fast-acting insulin analog.

The study of triglyceride (TG) metabolism using stable isotope tracers would be facilitated by being able to detect lowC enrichment. To meet this goal, we developed a gas chromatography/isotope ratio-mass spectrometry technique to measure the enrichment of palmitate in nonesterified fatty acids (NEFA) and TG as its methyl derivative. This method allows accurate and reproducible measurements of enrichment as low as 0.009 mole percent excess (MPE), in a range between 0-0.65 MPE. The usefulness of this method is shown by two studies of lipid metabolism in human beings. First, we studied the metabolic fate of an oral TG load labeled with [1,1,1-C]tripalmitin. Labeled palmitate appeared concurrently in plasma NEFA and TG, and four hours after the load, the labeling was higher in NEFA than in TG (MPE NEFA: 1.53±0.31 vs. MPE TG: 0.78±0.06, P<0.05). In a second study, the hepatic reesterification of NEFA was estimated by measuring the appearance of infused [1-C]palmitate in circulating TG. The estimated contribution of plasma NEFA to circulating TG increased to a maximum of 22%. Thus, gas chromatography/isotope ratio-mass spectrometry appears to be a useful tool for future studies of lipid metabolism in humans. [ABSTRACT FROM AUTHOR]

Objective We investigated whether loss of bone is detectable during follow-up of diabetic patients with chronic kidney disease (CKD). Research design and methods In 40 initially non-dialysed diabetic patients with CKD (isotopic glomerular filtration rate < 60 ml/min/1.73 m2 or albumin excretion rate > 30 mg/24 h), body composition (DEXA scan) and glomerular filtration rate (GFR determined from 51Cr-EDTA clearance) were measured at a 2-year interval, and compared by paired t-tests. Results The 40 patients, mainly with Type 2 diabetes ( n = 28), were men ( n = 28), aged 65 ± 11 years, with diabetes duration 18 ± 11 years. GFR was initially 38.0 (range 8–89) ml/min/1.73 m2. CKD progressed during follow-up: eight started haemodialysis and GFR declined in the 32 others ( P < 0.05 vs. initial). T-scores for total body (initial −0.61 ± 1.11, final −1.11 ± 1.40; P < 0.001) and femoral neck (initial −1.88 ± 0.15, final −2.07 ± 0.15; P < 0.05) declined. Ten patients were osteopaenic at baseline (no osteoporosis), whereas most were osteopaenic ( n = 21, P < 0.05) and five were osteoporotic at final assessment. The 16 patients who became osteopaenic or osteoporotic during follow-up did not differ from the others for the type of diabetes, age, GFR, albumin excretion rate, HbA1c, GFR reduction and the requirement for dialysis during follow-up. They were all men ( P < 0.01 by chi-squared test), with reduced initial total body T-score (−1.20 ± 0.82, others −0.32 ± 1.13; P < 0.05) and a lower body mass index (24.6 ± 4.3; others 27.7 ± 4.3; P < 0.05). Conclusion Bone loss, especially in the femoral neck, is progressive in diabetic patients with CKD. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the study that discusses the use of metformin according to estimated glomerular filtration rate.

Aims: We investigated whether Diabetic Retinopathy (DR) is related to Diabetic Foot Ulcer (DFU) development, adjusted for the stratification of the International Work Group on Diabetic Foot (IWGDF) guidance., Materials and Methods: DR and IWGDF stratification was registered retrospectively in patients hospitalised from 2009 to 2017 for uncontrolled and/or complicated type 2 diabetes. New DFUs were registered until 2020. Survival analyses categorised the subjects for DR, and multivariate Cox regression adjusted for confounders., Results: The 522 patients (57.9% male) were 62 ± 9 years old with a diabetes duration of 14 ± 10 years, HbA1c of 8.7 ± 1.8%, 33.9% macroangiopathies and 44.8% diabetic kidney diseases. Their grades of DFU risk were 0 for 43.3%, 1 for 23.9%, 2 for 7.1%, and 3 for 25.6%. During the 52 months follow-up (Inter Quartile Range: 32-71), 58 new DFUs and 18 lower-limb amputations occurred, mostly in patients with DR present in 140 (26.8%) patients. Adjusted for age, sex and conventional risk factors (duration and control of diabetes, arterial hypertension, and dyslipidemia), and other complications (macroangiopathy and diabetic kidney disease), DR was associated with a greater incidence of DFUs. Adjusted for the IWGDF classification, DR was related to new DFUs (HR: 2.51, 95%Confidence Interval [CI]: 1.48-4.26) and amputations (HR: 3.56, 95%CI: 1.26-10.07). This relationship persisted in ascending IWGDF grades with incidences of DFUs from 2/1000 (grade 0, no DR) to 121/1000 patient-years (grade 3 and DR) and amputations from 0 (grade 0, no DR) to 38/1000 patient-years (grade 3 and DR)., Conclusions: Diabetic retinopathy independently relates to the incidence of foot ulcers and amputations in patients hospitalised for type 2 diabetes., (© 2022 John Wiley & Sons Ltd.)

Aim: To assess whether periodontal treatment can lead to clinical, glycaemic control and quality of life improvements in metabolically unbalanced diabetic patients (type 1 or type 2) diagnosed with periodontitis., Methods: In this open-labelled randomized controlled trial, diabetic subjects (n = 91) were given "immediate" or "delayed" periodontal treatment (full-mouth non-surgical scaling and root planing, systemic antibiotics, and oral health instructions). The main outcome was the effect on glycated haemoglobin (HbA 1C ) and fructosamine levels. The General Oral Health Assessment Index and the SF-36 index were used to assess quality of life (QoL)., Results: Periodontal health significantly improved after periodontal treatment (p < 0.001). Periodontal treatment seemed to be safe but had no significant effects on glycaemic control based on HbA 1C (adjusted mean difference with a 95% confidence interval (aMD) of 0.04 [-0.16;0.24]) and fructosamine levels (aMD 5.0 [-10.2;20.2]). There was no obvious evidence of improvement in general QoL after periodontal treatment. However, there was significant improvement in oral health-related QoL (aMD 7.0 [2.4;11.6], p = 0.003)., Conclusion: Although periodontal treatment showed no clinical effect on glycaemic control in this trial, important data were provided to support periodontal care among diabetic patients. Periodontal treatment is safe and improves oral health-related QoL in patients living with diabetes. ISRCTN15334496., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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 m 2 ): 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., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background & Aims: Liver stiffness measurement (LSM) failure when using transient elastography occurs in 2-10% of patients, and is generally related to obesity. The aim of this prospective study was to assess the feasibility of LSM when using a new XL probe on patients with a body mass index (BMI) > or =30 kg/m(2)., Methods: For each patient, LSM was performed using both M probe (currently available and dedicated to patients with standard morphology) and XL probe (dedicated to overweighed patients). A blood sample was taken to assess usual biological variables and simple readily available fibrosis blood tests., Results: Ninety-nine patients were included (27 men, mean age 52 years, mean BMI 40.5 kg/m(2)). LSM was successful (10 valid measurements) in 45% of the cases with the M probe, vs 76% of the cases with the XL probe (P<0.001). Fifty-nine percent of those who could not be measured (<10 valid measurements) using the M probe could successfully be measured using the XL probe. In the 44 patients successfully measured with both probes, LSM was correlated with the platelet count, prothrombin time, gamma-glutamyltransferase, aspartate aminotransferase, fasting glucose, AST platelet ratio index, Forns score and FIB-4., Conclusion: The new XL probe allows providing a higher rate of LSM than the M probe in patients with an increased BMI and shows promising results for the evaluation of liver fibrosis.