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Journal Cover Diabetes & Metabolism
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   ISSN (Print) 1262-3636
   Published by Elsevier Homepage  [3175 journals]
  • Glucose variability: Do we have to revisit the profusion of definitions to
           avoid confusion'
    • Authors: L. Monnier; C. Colette; D. Owens
      Pages: 97 - 100
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): L. Monnier, C. Colette, D. Owens

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2017.10.005
  • Renal outcomes with dipeptidyl peptidase-4 inhibitors
    • Authors: A.J. Scheen; P. Delanaye
      Pages: 101 - 111
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): A.J. Scheen, P. Delanaye
      Dipeptidyl peptidase-4 inhibitors (DPP-4is) are increasingly being used in the management of type 2 diabetes (T2D). The present review summarizes the current knowledge of the effects of DPP-4is on renal outcomes by analyzing the experimental preclinical data, the effects of DPP-4is on urinary albumin–creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) from observational studies and clinical trials, and renal events (including kidney failure requiring renal replacement therapy) in recent large prospective cardiovascular outcome trials. Renal protection has been demonstrated in various animal models that have implicated different underlying mechanisms independent of glucose control, whereas prevention of new onset microalbuminuria and/or progression of albuminuria has been reported in some clinical studies, but with no significant effects on eGFR in most of them. The long-term clinical effects of DPP-4is on renal outcomes and the development of end-stage renal disease remain largely unknown and, thus, demand further investigations in prospective trials and long-term observational studies. In conclusion, despite promising results in animal models, data on surrogate biological markers of renal function and clinical renal outcomes remain rather scanty in patients with T2D, and mostly demonstrate the safety rather than true efficacy of DPP-4is.

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2017.07.011
  • Comparing SGLT-2 inhibitors to DPP-4 inhibitors as an add-on therapy to
           metformin in patients with type 2 diabetes: A systematic review and
    • Authors: B.M. Mishriky; R.J. Tanenberg; K.A. Sewell; D.M. Cummings
      Pages: 112 - 120
      Abstract: Publication date: Available online 7 February 2018
      Source:Diabetes & Metabolism
      Author(s): B.M. Mishriky, R.J. Tanenberg, K.A. Sewell, D.M. Cummings
      Aims Our aim was to compare Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) to Dipeptidyl peptidase-4 inhibitors (DPP-4i) as add-on therapy to metformin. Methods We searched for randomized trials comparing SGLT-2i to DPP-4i as add-on therapy to metformin in Type 2 diabetes.We pooled trials reporting outcomes between 12 and 26 weeks together while trials reporting results ≥52 weeks were pooled together. The primary outcomes were the change in haemoglobin A1c (A1c) at ≤26 and ≥52 weeks. Sensitivity analyses were performed according to the dose of SGLT-2i and according to baseline A1c for the primary outcomes. Results Seven trials met our inclusion criteria. There was a statistically significant reduction in A1c at ≥52 weeks favouring SGLT-2i compared to DPP-4i (MD [95% CI]=−0.11% [−0.20, −0.03]) but no significant difference at ≤26 weeks (MD [95% CI]=−0.05% [−0.16, 0.05]). SGLT-2i caused significantly more weight loss compared to DPP-4i at ≤26 weeks and ≥52 weeks (MD [95% CI]=−2.31kg [−2.66, −1.96] and −2.45kg [−2.83, −2.07], respectively). SGLT-2i treated patients had a significantly more genital infection compared to DPP-4i. On restricting the analysis according to the SGLT-2i FDA-approved dose, only higher doses at ≥52 weeks showed a statistically significant reduction in A1c compared to DPP-4i. On restricting the analysis according to baseline A1c, results favoured DPP-4i if baseline A1c was<8.5%, but favoured SGLT-2i if ≥8.5%. Conclusion While both SGLT-2i and DPP-4i can reduce A1c, SGLT-2i causes a more robust A1c reduction and more weight loss but with more genital infections. Higher doses of SGLT-2i showed more efficacy when compared to DPP-4i; however, this data should be interpreted cautiously given the limited number of trials.

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.01.017
  • Role of fatty liver in the association between obesity and reduced hepatic
           insulin clearance
    • Authors: Y. Matsubayashi; A. Yoshida; H. Suganami; H. Ishiguro; M. Yamamoto; K. Fujihara; S. Kodama; S. Tanaka; K. Kaku; H. Sone
      Pages: 135 - 142
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): Y. Matsubayashi, A. Yoshida, H. Suganami, H. Ishiguro, M. Yamamoto, K. Fujihara, S. Kodama, S. Tanaka, K. Kaku, H. Sone
      Aim Hepatic insulin clearance (HIC) is important in regulating plasma insulin levels. Diminished HIC causes inappropriate hyperinsulinaemia, and both obesity and fatty liver (FL), which are known to decrease HIC, can be found either together in the same patient or on their own. The mechanism by which obesity reduces HIC is presumed to be mediated by FL. However, few reports have examined the role of FL in the relationship between obesity and HIC in type 2 diabetes (T2D) patients. Therefore, our study investigated the association of HIC with clinical factors, including insulin sensitivity indices, focusing on the presence or absence of FL and obesity in T2D patients. Method Baseline data from 419 patients with T2D (279 men, 140 women; mean age: 57.6 years; body mass index: 25.5kg/m2) controlled by diet and exercise were analyzed. HIC was calculated from the ratio of fasting c-peptide to fasting insulin levels (HICCIR). Correlation analyses between HICCIR and clinical variables were performed using Pearson's product-moment correlation coefficients and single regression analysis in all participants and in those with obesity and FL either alone or in combination. Results HICCIR was significantly correlated with whole-body insulin sensitivity indices and influenced by FL, but only in the FL group was obesity independently influenced HIC level. HICCIR decreased in those with both FL and obesity compared with those with only one such complication. Conclusion HICCIR may be used to evaluate whole-body insulin sensitivity in T2D. Also, compared with obesity, the influence of FL strongly contributed to a reduced HIC. Trial registration number These trials were registered by the Japan Pharmaceutical Information Centre clinical trials information (JapicCTI) as 101349 and 101351.

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2017.12.003
  • Fenofibrate decreases plasma ceramide in type 2 diabetes patients: A novel
           marker of CVD'
    • Authors: M. Croyal; Z. Kaabia; L. León; S. Ramin-Mangata; T. Baty; F. Fall; S. Billon-Crossouard; A. Aguesse; T. Hollstein; D.R. Sullivan; E. Nobecourt; G. Lambert; M. Krempf
      Pages: 143 - 149
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): M. Croyal, Z. Kaabia, L. León, S. Ramin-Mangata, T. Baty, F. Fall, S. Billon-Crossouard, A. Aguesse, T. Hollstein, D.R. Sullivan, E. Nobecourt, G. Lambert, M. Krempf
      Aim The benefit of the lipid-lowering drug fenofibrate on cardiovascular outcomes is controversial. Our aim was to find new circulating markers to identify those patients most likely to benefit from fenofibrate prescription. Methods Analyses were conducted of plasma samples collected from 102 patients with type 2 diabetes, enrolled in the FIELD trial, before and after fenofibrate treatment (200mg/day). Non-targeted and targeted lipid analyses and apolipoprotein measurements were made using mass spectrometry methods. Results Lipidomics revealed a global decrease in ceramide after fenofibrate treatment confirmed by quantitative analysis (−18.2%, P <0.001). These changes were strongly associated with those found for plasma sphingomyelin (r =0.80, P <0.001) and, to a lesser extent, for sphingosine-1-phosphate (r =0.34, P <0.001). Ceramide levels decreased in 73.5% of patients. In addition to the expected lipid changes (decreases in triglycerides, total cholesterol and LDL cholesterol, and increase in HDL cholesterol), fenofibrate also lowered plasma apoC-II (−11.1%, P <0.01), apoC-III (−24.6%; P <0.001), apoB100 (−27.0%, P <0.01) and sphingomyelinase (−7.6%, P <0.001), and increased plasma apoA-II (22.4%, P <0.001) as well as adiponectin (11.4%, P <0.001). No significant association was found between ceramide decrease and these modulations except for total cholesterol (r =0.20, P =0.047) and HDL protein components. At baseline, only elevated sphingolipid levels were significantly associated with ceramide reduction after fenofibrate treatment. Conclusion Fenofibrate lowers plasma ceramide independently of the usual lipid parameters. As ceramide is a strong marker of atherosclerosis, our study underpins the need to further evaluate its contribution to cardiovascular events in fenofibrate-treated patients.

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2017.04.003
  • The brown-fat-secreted adipokine neuregulin 4 is decreased in gestational
           diabetes mellitus
    • Authors: S. Kralisch; A. Hoffmann; J. Kratzsch; M. Blüher; M. Stumvoll; M. Fasshauer; T. Ebert
      Pages: 150 - 154
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): S. Kralisch, A. Hoffmann, J. Kratzsch, M. Blüher, M. Stumvoll, M. Fasshauer, T. Ebert
      Aims Neuregulin 4 has recently been recognized as a novel adipokine secreted by brown adipose tissue (BAT), with beneficial effects on murine insulin resistance and hepatic steatosis. Yet, thus far, neither regulation of neuregulin 4 in gestational diabetes mellitus (GDM) nor its longitudinal changes in the peripartum period have been elucidated. Methods Circulating neuregulin 4 levels were measured by ELISA in 74 women with GDM and 74 healthy, gestational-age-matched controls. Also, neuregulin 4 was quantified during pregnancy and compared with postpartum levels in a follow-up study of 25 women with previous GDM and 25 healthy control women. Results Women with GDM had lower median serum levels of the novel BAT-secreted adipokine neuregulin 4 (3.0μg/L) compared with healthy (non-GDM) pregnant controls (3.5μg/L; P =0.020), and the area under the glucose curve (AUCGlucose) was an independent and negative predictor of circulating neuregulin 4 (P =0.033). Also, median postpartum serum concentrations of neuregulin 4 (3.2μg/L) were not significantly different from prepartum levels (2.8μg/L; P =0.328). In addition, neuregulin 4 was positively and independently associated with irisin (P =0.009), but not other BAT-secreted adipokines. Conclusion/interpretation Women with GDM have significantly lower circulating neuregulin 4 levels compared with healthy pregnant controls, and the AUCGlucose is negatively and independently associated with neuregulin 4 during pregnancy. Neuregulin 4 is positively correlated with irisin during pregnancy, as well as in a longitudinal fashion. Future studies are now needed to better elucidate the precise pathomechanisms of the regulation of BAT-secreted adipokines during pregnancy.

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2017.06.001
  • Family history of diabetes is associated with enhanced adipose lipolysis:
           Evidence for the implication of epigenetic factors
    • Authors: I. Dahlman; M. Ryden; P. Arner
      Pages: 155 - 159
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): I. Dahlman, M. Ryden, P. Arner
      Aims Type 2 diabetes is associated with insulin resistance, adipose hypertrophy and increased lipolysis. The heritability of these traits has been determined by associating them with a family history of diabetes. Methods Abdominal subcutaneous fat biopsies were obtained from 581 subjects in a cross-sectional study. Fat cells were isolated, and the difference between measured and expected fat-cell volume was used to determine adipose morphology (degree of hypertrophy or hyperplasia). Spontaneous lipolytic activity was determined in explants of adipose tissue by measuring glycerol release. Insulin-stimulated lipogenesis was assessed by measuring the incorporation of radiolabelled glucose into fat-cell lipids. Information on parental history of diabetes was gathered by a questionnaire. Results Adipose morphology correlated positively with lipolysis (P <0.0001) and inversely with insulin-stimulated lipogenesis (P <0.008). Also, 24% of probands had a family history of diabetes, which was associated with higher body mass index (BMI) scores, and more insulin resistance (HOMAIR) and adipose hypertrophy. Lipolytic activity was increased, and insulin-stimulated lipogenesis decreased, in probands with a parental history of diabetes. The results for HOMAIR, lipolysis and adipose morphology remained significant after adjusting for proband BMI. A maternal history of diabetes was associated with increased adipose lipolytic activity in probands. Conclusion A family history of diabetes is independent of proband BMI, but associated with adipocyte hypertrophy and enhanced lipolysis, which suggests that these factors are genetically linked to diabetes. Moreover, the influence on lipolysis was only observed in probands with a maternal history of diabetes, thereby supporting an epigenetic impact.

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2017.10.010
  • Carbamylation is a competitor of glycation for protein modification in
    • Authors: C. Nicolas; S. Jaisson; L. Gorisse; F.J. Tessier; C. Niquet-Léridon; P. Jacolot; C. Pietrement; P. Gillery
      Pages: 160 - 167
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): C. Nicolas, S. Jaisson, L. Gorisse, F.J. Tessier, C. Niquet-Léridon, P. Jacolot, C. Pietrement, P. Gillery
      Aim Chronic kidney disease (CKD) and diabetes mellitus are two diseases that accelerate protein molecular ageing through carbamylation and glycation reactions, characterized by the binding of urea-derived isocyanic acid and of sugars on proteins, respectively. These two reactions target the same protein amino groups and, thus, compete with each other. Such competition may arise especially in diabetic patients with nephropathy. This study aimed to evaluate their potential competitive effects in vitro and under conditions reproducing CKD and/or diabetes in vivo. Methods Albumin was incubated in vitro with glucose, urea or cyanate. Carbamylation in vivo was enhanced in normal and diabetic (db/db) mice by either subtotal nephrectomy or cyanate consumption. Homocitrulline, carbamylated haemoglobin and furosine were measured by LC–MS/MS, fructosamine by colorimetric assay and HbA1c by immunological assay. Results Reciprocal inhibition between carbamylation and glycation was observed during albumin incubations in vitro. Besides, 5 weeks after induction of CKD in vivo, plasma homocitrulline concentrations were similar in both diabetic and non-diabetic mice, whereas fructosamine and HbA1c were decreased (−23% and −42%, respectively) in diabetic mice with CKD compared with only diabetic ones. Fructosamine and HbA1c were also decreased in cyanate-spiked water-drinking mice compared with plain water-drinking diabetic mice. Conclusion Carbamylation competes with glycation in vivo, especially under conditions of high glycation. Thus, the classic markers of glycaemic control should be interpreted with caution in diabetic patients with CKD because of this competitive effect.

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2017.05.006
  • Can persistent organic pollutants distinguish between two opposite
           metabolic phenotypes in lean Koreans'
    • Authors: K.H. Ha; S.A. Kim; Y.M. Lee; D.J. Kim; D.H. Lee
      Pages: 168 - 171
      Abstract: Publication date: Available online 6 January 2018
      Source:Diabetes & Metabolism
      Author(s): Kyoung Hwa Ha, Se-A Kim, Yu-Mi Lee, Dae Jung Kim, Duk-Hee Lee
      Aims This study investigated the association of persistent organic pollutants (POPs), an emerging new risk factor for type 2 diabetes and the metabolic syndrome, with the presence of opposite phenotypes of glucose and lipid metabolism among normal-weight Koreans of similar body composition. Methods Fifty subjects, randomly selected from an ongoing community-based cohort study, from two opposite phenotype groups—metabolically unhealthy normal weight (MUHNW) and metabolically heathy normal weight (MHNW)—were matched for waist circumference, visceral fat mass and demographic variables, then compared for serum concentrations of POPs. Results Most POPs (10 out of 13 compounds) were present in higher serum concentrations in the MUHNW than in the MHNW. In particular, serum concentrations of all compounds of the organochlorine pesticide class were 2.2 to 4.7 times higher in cases than in controls. Compared with the lowest tertile of summary measures of POPs, ORs (95% CIs) for the second and third tertiles were 7.4 (1.9–29.4) and 10.4 (2.6–41.2), respectively. Adjusting for possible confounders did not change the results. Conclusion Taken altogether, these findings from the present and previous studies suggest that increased serum POP concentrations may play an important role in the development of unhealthy metabolic phenotypes in lean people.

      PubDate: 2018-01-10T08:58:52Z
      DOI: 10.1016/j.diabet.2017.12.008
  • Predictors of the response of HbA1c and body weight after SGLT2 inhibition
    • Authors: T. Abe; Y. Matsubayashi; A. Yoshida; H. Suganami; T. Nojima; T. Osawa; M. Ishizawa; M. Yamamoto; K. Fujihara; S. Tanaka; K. Kaku; H. Sone
      Pages: 172 - 174
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): T. Abe, Y. Matsubayashi, A. Yoshida, H. Suganami, T. Nojima, T. Osawa, M. Ishizawa, M. Yamamoto, K. Fujihara, S. Tanaka, K. Kaku, H. Sone

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2017.10.003
  • Hypoglycaemia causes both daytime and nighttime QTc interval prolongation
           in patients with type 2 diabetes receiving insulin treatment
    • Authors: K. Makrilakis; C. Stathi; I. Vlahodimitris; S. Kalopita; P. Thomakos; P. Konstantopoulos; D. Perrea; N. Katsilambros; S. Liatis
      Pages: 175 - 177
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): K. Makrilakis, C. Stathi, I. Vlahodimitris, S. Kalopita, P. Thomakos, P. Konstantopoulos, D. Perrea, N. Katsilambros, S. Liatis

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2017.08.005
  • Glycated albumin predicts the development of early diabetic nephropathy in
           patients with type 2 diabetes
    • Authors: J.E. Jun; K.Y. Hur; Y.-B. Lee; S.-E. Lee; S.-M. Jin; M.-K. Lee; J.H. Kim
      Pages: 178 - 180
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): J.E. Jun, K.Y. Hur, Y.-B. Lee, S.-E. Lee, S.-M. Jin, M.-K. Lee, J.H. Kim

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2017.08.003
  • Plasma trans-palmitoleic acid is associated with cardio-metabolic risk
           factors in youth with type 1 diabetes
    • Authors: N.S. The; I.B. King; S.C. Couch; J.L. Crandell; D. Dabelea; A.D. Liese; E.J. Mayer-Davis
      Pages: 181 - 184
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): N.S. The, I.B. King, S.C. Couch, J.L. Crandell, D. Dabelea, A.D. Liese, E.J. Mayer-Davis

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2017.02.004
  • Diabetes remission after bariatric surgery in obese patients with
    • Authors: F. Phan; C. Vatier; C. Vauloup-Soupault; C. Poitou; J.-L. Bouillot; J.-M. Oppert; J. Aron-Wisnewsky
      Pages: 185 - 187
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): F. Phan, C. Vatier, C. Vauloup-Soupault, C. Poitou, J.-L. Bouillot, J.-M. Oppert, J. Aron-Wisnewsky

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2017.02.005
  • Comparison of simple indices for measuring insulin resistance that
           integrates adipokines in non-diabetic obese postmenopausal women before
           and after weight loss: A MONET study
    • Authors: C. Vatier; S. Fellahi; A.D. Karelis; M. Brochu; E. Doucet; D. Prud’homme; R. Rabasa-Lhoret; J.-P. Bastard
      Pages: 190 - 191
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): C. Vatier, S. Fellahi, A.D. Karelis, M. Brochu, E. Doucet, D. Prud’homme, R. Rabasa-Lhoret, J.-P. Bastard

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2017.04.006
  • Changes in glucose-lowering drug use before and after cancer diagnosis in
           patients with diabetes
    • Authors: M.M.J. Zanders; H.R. Haak; M.P.P. van Herk-Sukel; R.M.C. Herings; L.V. van de Poll-Franse; J.A. Johnson
      Pages: 22 - 29
      Abstract: Publication date: February 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 1
      Author(s): M.M.J. Zanders, H.R. Haak, M.P.P. van Herk-Sukel, R.M.C. Herings, L.V. van de Poll-Franse, J.A. Johnson
      Aim This study explores the changes in glucose-lowering drug (GLD) use before and after cancer diagnosis among patients with diabetes. Methods New GLD users (1998–2011) living in the Dutch ECR–PHARMO catchment area were selected from the PHARMO Database Network (n =52,228). Those with a primary cancer diagnosis were considered cases (n =3281) and matched with eligible controls (n =12,891) without cancer during follow-up. Conditional logistic regression analysis was used to assess changes in GLD use, such as treatment add-ons, treatments drops and initiation of insulin, for cases compared with controls associated with specific cancer types in four time windows (6–3 and 0–3months before cancer diagnosis; 0–3 and 3–6months after cancer diagnosis). Results In the 3months before cancer diagnosis, patients with upper gastrointestinal (GI) cancers (oesophageal, stomach, pancreatic, liver cancers) had higher odds of initiating insulin (OR: 9.3; 95% CI: 3.6–24.1); to a lesser extent, this was also observed in the 3months prior to that (at 6months, OR: 3.9; 95% CI: 1.3–12.1). Diagnosis of colorectal (OR: 3.4; 95% CI: 1.4–8.4), pulmonary (OR: 2.5; 95% CI: 1.1–5.4) and upper GI (OR: 13.6; 95% CI: 5.0–36.9) cancers was associated with increased odds of initiating insulin in the 3months after cancer diagnosis. During all study time windows, the odds of treatment drops were higher for patients with upper GI cancers whereas, for most other cancers, these odds were higher only after a diagnosis of cancer. Conclusion The greater odds of initiating insulin during the 6months prior to diagnosis of upper GI cancers suggest reverse causation. After cancer diagnosis, drops in use of GLDs was commonly seen.

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2017.08.004
  • Subcutaneous advanced glycation end-products and lung function according
           to glucose abnormalities: The ILERVAS Project
    • Authors: Enric Sánchez; Albert Lecube; Àngels Betriu; Cristina Hernández; Carolina López-Cano; Liliana Gutiérrez-Carrasquilla; Mohsen Kerkeni; Andree Yeramian; Francesc Purroy; Reinald Pamplona; Cristina Farràs; Elvira Fernández; Ferrán Barbé; Rafael Simó
      Abstract: Publication date: Available online 13 April 2018
      Source:Diabetes & Metabolism
      Author(s): Enric Sánchez, Albert Lecube, Àngels Betriu, Cristina Hernández, Carolina López-Cano, Liliana Gutiérrez-Carrasquilla, Mohsen Kerkeni, Andree Yeramian, Francesc Purroy, Reinald Pamplona, Cristina Farràs, Elvira Fernández, Ferrán Barbé, Rafael Simó

      PubDate: 2018-04-15T12:10:34Z
      DOI: 10.1016/j.diabet.2018.04.002
  • Impact of sex and glucose-lowering treatments on hypoglycaemic symptoms in
           people with type 2 diabetes and chronic kidney disease. The French Chronic
           Kidney Disease – Renal Epidemiology and Information Network (CKD-REIN)
    • Authors: Beverley Balkau; Marie Metzger; Fabrizio Andreelli; Luc Frimat; Elodie Speyer; Christian Combe; Maurice Laville; Christian Jacquelinet; Serge Briançon; Carole Ayav; Ziad Massy; Ronald L. Pisoni; Bénédicte Stengel; Denis Fouque
      Abstract: Publication date: Available online 6 April 2018
      Source:Diabetes & Metabolism
      Author(s): Beverley Balkau, Marie Metzger, Fabrizio Andreelli, Luc Frimat, Elodie Speyer, Christian Combe, Maurice Laville, Christian Jacquelinet, Serge Briançon, Carole Ayav, Ziad Massy, Ronald L. Pisoni, Bénédicte Stengel, Denis Fouque
      Aim To describe current practices of glucose-lowering treatments in people with diabetes and chronic kidney disease (CKD), the associated glucose control and hypoglycaemic symptoms, with an emphasis on sex differences. Methods Among the 3033 patients with CKD stages 3 to 5 recruited into the French CKD-REIN study, 645 men and 288 women had type 2 diabetes and were treated by glucose-lowering drugs. Results Overall, 31% were treated only with insulin, 28% with combinations of insulin and another drug, 42% with non-insulin glucose-lowering drugs. In CKD stage 3, 40% of patients used metformin, 12% at stages 4&5, similar for men and women; in CKD stage 3, 53% used insulin, similar for men and women, but at stages 4&5, 59% of men and 77% of women used insulin. Patients were reasonably well controlled, with a median HbA1c of 7.1% (54 mmol/mol) in men, 7.4% (57 mmol/mol) in women (P = 0.0003). Hypoglycaemic symptoms were reported by 40% of men and 59% of women; they were not associated with the estimated glomerular filtration rate, nor with albuminuria or with HbA1c in multivariable analyses, but they were more frequent in people treated with insulin, particularly with fast-acting and pre-mixed insulins. Conclusion Glucose-lowering treatment, HbA1c and hypoglycaemic symptoms were sex dependent. Metformin use was similar in men and women, but unexpectedly low in CKD stage 3; its use could be encouraged rather than resorting to insulin. Hypoglycaemic symptoms were frequent and need to be more closely monitored, with appropriate patient-education, especially in women.

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2018.03.007
  • Effects of 6 vs 3 eucaloric meal patterns on glycaemic control and satiety
           in people with impaired glucose tolerance or overt type 2 diabetes: A
           randomized trial
    • Authors: E. Papakonstantinou; M.D. Kontogianni; P. Mitrou; E. Magriplis; D. Vassiliadi; T. Nomikos; V. Lambadiari; E. Georgousopoulou; G. Dimitriadis
      Abstract: Publication date: Available online 6 April 2018
      Source:Diabetes & Metabolism
      Author(s): E. Papakonstantinou, M.D. Kontogianni, P. Mitrou, E. Magriplis, D. Vassiliadi, T. Nomikos, V. Lambadiari, E. Georgousopoulou, G. Dimitriadis
      Background/objectives The study aimed to compare the effects of two eucaloric meal patterns (3 vs 6 meals/day) on glycaemic control and satiety in subjects with impaired glucose tolerance and plasma glucose (PG) levels 140–199mg/dL at 120min (IGT-A) or PG levels 140–199mg/dL at 120min and >200mg/dL at 30/60/90min post-oral glucose load on 75-g OGTT (IGT-B), or overt treatment-naïve type 2 diabetes (T2D). Subjects/methods In this randomized crossover study, subjects with IGT-A (n =15, BMI: 32.4±5.2kg/m2), IGT-B (n =20, BMI: 32.5±5kg/m2) or T2D (n =12, BMI: 32.2±5.2kg/m2) followed a weight-maintenance diet (45% carbohydrates, 20% proteins, 35% fats) in 3 or 6 meals/day (each intervention lasting 12 weeks). Anthropometrics, diet compliance and subjective appetite were assessed every 2 weeks. OGTT and measurements of HbA1c and plasma lipids were performed at the beginning and end of each intervention period. Results Body weight and physical activity levels remained stable throughout the study. In T2D, HbA1c and PG at 120min post-OGTT decreased with 6 vs 3 meals (P <0.001 vs P =0.02, respectively). The 6-meal also intervention improved post-OGTT hyperinsulinaemia in IGT-A subjects and hyperglycaemia in IGT-B subjects. In all three groups, subjective hunger and desire to eat were reduced with 6 vs 3 meals/day (P <0.05). There were no differences in HOMA-IR or plasma lipids between interventions. Conclusion Although weight loss remains the key strategy in hyperglycaemia management, dietary measures such as more frequent and smaller meals may be helpful for those not sufficiently motivated to adhere to calorie-restricted diets. Our study shows that 6 vs 3 meals a day can increase glycaemic control in obese patients with early-stage T2D, and may perhaps improve and/or stabilize postprandial glucose regulation in prediabetes subjects.

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2018.03.008
  • Lipoprotein(a) levels are doubled in left-handed patients with diabetes
    • Authors: M.P. Hermans; S.A. Ahn; M.F. Rousseau
      Abstract: Publication date: Available online 28 March 2018
      Source:Diabetes & Metabolism
      Author(s): M.P. Hermans, S.A. Ahn, M.F. Rousseau

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2018.03.005
  • Very high titres of ZnT8 autoantibodies at type 1 diabetes onset and
           presence of autoantibodies related to other autoimmune disorders
    • Authors: L. Marchand; L. Garnier; C. Thivolet; M. Nicolino; N. Fabien
      Abstract: Publication date: Available online 22 March 2018
      Source:Diabetes & Metabolism
      Author(s): L. Marchand, L. Garnier, C. Thivolet, M. Nicolino, N. Fabien

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2018.03.003
  • Prevalence and clinical characteristics of non-alcoholic fatty liver
           disease in newly diagnosed patients with ketosis-onset diabetes
    • Authors: T.-T. Li; A.-P. Wang; J.-X. Lu; M.-Y. Chen; C.-C. Zhao; Z.-H. Tang; L.-X. Li; W.-P. Jia
      Abstract: Publication date: Available online 21 March 2018
      Source:Diabetes & Metabolism
      Author(s): T.-T. Li, A.-P. Wang, J.-X. Lu, M.-Y. Chen, C.-C. Zhao, Z.-H. Tang, L.-X. Li, W.-P. Jia
      Aim As the prevalence and clinical characteristics of non-alcoholic fatty liver disease (NAFLD) are still unknown in ketosis-onset diabetes, the present study compared the characteristics of NAFLD in type 1 diabetes (T1D), ketosis-onset and non-ketotic type 2 diabetes (T2D) patients. Methods This cross-sectional study was performed with newly diagnosed Chinese patients with diabetes, including 39 T1D, 165 ketosis-onset and 173 non-ketotic T2D, with 30 non-diabetics included as controls. NAFLD was determined by hepatic ultrasonography, then its clinical features were analyzed and its associated risk factors evaluated. Results NAFLD prevalence in patients with ketosis-onset diabetes (61.8%) was significantly higher than in controls (23.3%; P =0.003) and in T1D patients (15.4%; P <0.001). However, there was no difference in prevalence between ketosis-onset and non-ketotic T2D patients (52.6%; P =0.229), although BMI and alanine aminotransferase (ALT) proved to be independent risk factors for the presence of NAFLD in both these groups whereas, in T1D patients, serum uric acid levels were independent risk factors. Conclusion NAFLD prevalence and risk factors in ketosis-onset diabetes were similar to those in non-ketotic T2D, but different from those in T1D. These data provide further evidence that ketosis-onset diabetes should be classified as a subtype of T2D rather than idiopathic T1D.

      PubDate: 2018-04-11T11:30:39Z
      DOI: 10.1016/j.diabet.2018.03.002
  • A decrease in glutamic acid decarboxylase autoantibody levels with
           sitagliptin use in patients with latent autoimmune diabetes in adults
    • Authors: Yanai
      Abstract: Publication date: March 2018
      Source:Diabetes & Metabolism, Volume 44, Issue 2
      Author(s): H. Yanai

      PubDate: 2018-04-11T11:30:39Z
  • Metformin-associated lactic acidosis: are we looking in the right
    • Authors: F.M. Trovato; G.F. Martines; P. Noto; G. Mangano; L. Malatino; G. Carpinteri
      Abstract: Publication date: Available online 15 March 2018
      Source:Diabetes & Metabolism
      Author(s): Francesca M. Trovato, Giuseppe F. Martines, Paola Noto, Giuseppe Mangano, Lorenzo Malatino, Giuseppe Carpinteri

      PubDate: 2018-03-18T09:25:57Z
      DOI: 10.1016/j.diabet.2018.03.001
  • The application of simple metrics in the assessment of glycaemic
    • Authors: L. Monnier; C. Colette; D.R. Owens
      Abstract: Publication date: Available online 6 March 2018
      Source:Diabetes & Metabolism
      Author(s): L. Monnier, C. Colette, D.R. Owens
      The assessment of glycaemic variability (GV) remains a subject of debate with many indices proposed to represent either short- (acute glucose fluctuations) or long-term GV (variations of HbA1c). For the assessment of short-term within-day GV, the coefficient of variation for glucose (%CV) defined as the standard deviation adjusted on the 24-h mean glucose concentration is easy to perform and with a threshold of 36%, recently adopted by the International Consensus on use of continuous glucose monitoring, separating stable from labile glycaemic states. More complex metrics such as the LBGI (Low Blood Glucose Index) or HBGI (High Blood Glucose Index) allow the risk of hypo or hyperglycaemic episodes, respectively to be assessed although in clinical practice its application is limited due to the need for more complex computation. This also applies to other indices of short-term intraday GV including the Mean Amplitude of Glycemic Excursions (MAGE), Shlichtkrull's M-value and CONGA. GV is important clinically as exaggerated glucose fluctuations are associated with an enhanced risk of adverse cardiovascular outcomes due primarily to hypoglycaemia. In contrast, there is at present no compelling evidence that elevated short-term GV is an independent risk factor of microvascular complications of diabetes. Concerning long-term GV there are numerous studies supporting its association with an enhanced risk of cardiovascular events. However, this association raises the question as to whether the impact of long-term variability is not simply the consequence of repeated exposure to short-term GV or ambient chronic hyperglycaemia. The renewed emphasis on glucose monitoring with the introduction of continuous glucose monitoring technologies can benefit from the introduction and application of simple metrics for describing GV along with supporting recommendations.

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.02.008
  • Plasma fetuin-B concentrations are associated with insulin resistance and
           first-phase glucose-stimulated insulin secretion in individuals with
           different degrees of glucose tolerance
    • Authors: H. Qu; Y. Qiu; Y. Wang; Y. Liao; Y. Zheng; H. Zheng
      Abstract: Publication date: Available online 22 February 2018
      Source:Diabetes & Metabolism
      Author(s): H. Qu, Y. Qiu, Y. Wang, Y. Liao, Y. Zheng, H. Zheng
      Aims To assess circulating fetuin-B concentrations in subjects with different degrees of glucose tolerance and to analyze the association of fetuin-B concentrations with insulin resistance and the first phase of glucose-stimulated insulin secretion. Methods Plasma fetuin-B concentrations were analyzed in 149 subjects with normal glucose tolerance (NGT, n =54), impaired glucose regulation (preDM, n =42) and newly diagnosed type-2 diabetes mellitus (nT2DM, n =53). Intravenous glucose tolerance tests (IVGTTs) and biochemical parameters were also assessed in all participants. Results Plasma fetuin-B concentrations were significantly higher in nT2DM patients compared with NGT and preDM subjects (both P <0.001) and positively correlated with FPG, 2hPG, HOMA-IR, HbA1c, hsCRP, FINS and TG (P <0.05), but negatively correlated with AIR, AUC, GDI and fasting Belfiore index (P <0.01). After adjusting for age and gender, all correlations remained statistically significant (P <0.05). Multivariate logistic regression analysis revealed that plasma fetuin-B concentrations were significantly correlated with nT2DM after controlling for age, gender, BMI, WHR, blood pressure and lipid profiles. Conclusion Patients with nT2DM have significantly higher concentrations of plasma fetuin-B compared with NGT subjects and plasma fetuin-B is strongly associated with glucose and lipid metabolism, chronic inflammation and first-phase glucose-stimulated insulin secretion and insulin resistance.

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.02.003
  • Therapy with cholesteryl ester transfer protein (CETP) inhibitors and
           diabetes risk
    • Authors: W. Masson; M. Lobo; D. Siniawski; M. Huerín; G. Molinero; R. Valéro; J.P. Nogueira
      Abstract: Publication date: Available online 20 February 2018
      Source:Diabetes & Metabolism
      Author(s): W. Masson, M. Lobo, D. Siniawski, M. Huerín, G. Molinero, R. Valéro, J.P. Nogueira
      Background Cholesteryl ester transfer protein (CETP) inhibitors are a class of drugs that targets the CETP enzyme to significantly increase serum high-density lipoprotein cholesterol (HDL-C) and decrease low-density lipoprotein cholesterol (LDL-C) levels. As HDL-C has potential antidiabetic properties, and the beneficial effects of CETP drugs on glucose homoeostasis have not been sufficiently studied, the aims of this study were: (1) to evaluate the effect of CETP inhibitors on the incidence of diabetes; and (2) to assess the association between CETP inhibitor-induced changes in HDL-C levels and incidence of diabetes. Methods A meta-analysis was performed of randomized controlled clinical trials of CETP inhibitor therapy, either alone or combined with other lipid-lowering drugs, reporting data from new cases of diabetes with a minimum of 6 months of follow-up, after searching the PubMed/MEDLINE, Embase and Cochrane Controlled Trials databases. A fixed-effects meta-regression model was then applied. Results Four eligible trials of CETP inhibitors, involving a total of 73,479 patients, were considered for the analyses, including 960 newly diagnosed cases of diabetes in the CTEP inhibitor group vs 1086 in the placebo group. CETP inhibitor therapy was associated with a significant 12% reduction in incidence of diabetes (OR: 0.88, 95% CI: 0.81–0.96; P =0.005). Assessment of the relationship between on-treatment HDL-C and the effect of CETP inhibitors showed a statistically non-significant trend (Z =–1.13, P =0.26). Conclusion CETP inhibitors reduced the incidence of diabetes. The improvement in glucose metabolism may have been related, at least in part, to the increase in HDL-C concentration.

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.02.005
  • Non-targeted metabolomic biomarkers and metabotypes of type 2 diabetes: A
           cross-sectional study of PREDIMED trial participants
    • Authors: M. Urpi-Sarda; E. Almanza-Aguilera; R. Llorach; R. Vázquez-Fresno; R. Estruch; D. Corella; J.V. Sorli; F. Carmona; A. Sanchez-Pla; J. Salas-Salvadó; C. Andres-Lacueva
      Abstract: Publication date: Available online 20 February 2018
      Source:Diabetes & Metabolism
      Author(s): M. Urpi-Sarda, E. Almanza-Aguilera, R. Llorach, R. Vázquez-Fresno, R. Estruch, D. Corella, J.V. Sorli, F. Carmona, A. Sanchez-Pla, J. Salas-Salvadó, C. Andres-Lacueva
      Aim To characterize the urinary metabolomic fingerprint and multi-metabolite signature associated with type 2 diabetes (T2D), and to classify the population into metabotypes related to T2D. Methods A metabolomics analysis using the 1H-NMR-based, non-targeted metabolomic approach was conducted to determine the urinary metabolomic fingerprint of T2D compared with non-T2D participants in the PREDIMED trial. The discriminant metabolite fingerprint was subjected to logistic regression analysis and ROC analyses to establish and to assess the multi-metabolite signature of T2D prevalence, respectively. Metabotypes associated with T2D were identified using the k-means algorithm. Results A total of 33 metabolites were significantly different (P <0.05) between T2D and non-T2D participants. The multi-metabolite signature of T2D comprised high levels of methylsuccinate, alanine, dimethylglycine and guanidoacetate, and reduced levels of glutamine, methylguanidine, 3-hydroxymandelate and hippurate, and had a 96.4% AUC, which was higher than the metabolites on their own and glucose. Amino-acid and carbohydrate metabolism were the main metabolic alterations in T2D, and various metabotypes were identified in the studied population. Among T2D participants, those with a metabotype of higher levels of phenylalanine, phenylacetylglutamine, p-cresol and acetoacetate had significantly higher levels of plasma glucose. Conclusion The multi-metabolite signature of T2D highlights the altered metabolic fingerprint associated mainly with amino-acid, carbohydrate and microbiota metabolism. Metabotypes identified in this patient population could be related to higher risk of long-term cardiovascular events and therefore require further studies. Metabolomics is a useful tool for elucidating the metabolic complexity and interindividual variation in T2D towards the development of stratified precision nutrition and medicine. Trial registration at ISRCTN35739639.

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.02.006
  • Clinical perspectives from the BEGIN and EDITION programmes: Trial-level
           meta-analyses outcomes with either degludec or glargine 300U/mL vs
           glargine 100U/mL in T2DM
    • Authors: R. Roussel; R. Ritzel; E. Boëlle-Le Corfec; B. Balkau; J. Rosenstock
      Abstract: Publication date: Available online 19 February 2018
      Source:Diabetes & Metabolism
      Author(s): R. Roussel, R. Ritzel, E. Boëlle-Le Corfec, B. Balkau, J. Rosenstock
      Aims To explore comparative glycaemic control and hypoglycaemia incidence with insulin degludec 100U/mL (IDeg) or insulin glargine 300U/mL (Gla-300) versus glargine 100U/mL (Gla-100) in trial-level meta-analyses of phase 3a clinical trials including people with type-2 diabetes. Methods Meta-analyses of HbA1c, fasting plasma glucose (FPG), average 24h self-measured plasma glucose (SMPG), pre-breakfast SMPG and hypoglycaemia incidence and rate, using data from the BEGIN (IDeg) and EDITION (Gla-300) insulin development programmes, were performed. Results In BEGIN, despite greater FPG reduction with IDeg than Gla-100, HbA1c reduction was greater with Gla-100 (mean difference [95% CI] in HbA1c change: 0.09 [0.01–0.18] %) whereas in EDITION, there was no difference in FPG and HbA1c reduction between Gla-300 and Gla-100. Risk of nocturnal confirmed (<3.1mmol/L [<56mg/dL]) or severe hypoglycaemia, but not anytime (24h) events, was lower with IDeg than Gla-100 (relative risk [RR] 0.79 [0.66–0.94]) whereas Gla-300 was associated with reduced risk of nocturnal (RR 0.75 [0.61–0.92]) and anytime (24h) (RR 0.81 [0.69–0.94]) confirmed (<3.0mmol/L [<54mg/dL]) or severe hypoglycaemia versus Gla-100. Conclusions These trial-level meta-analyses suggest that despite greater reductions in FPG, IDeg was associated with less improvement in HbA1c versus Gla-100, with a hypoglycaemia benefit only evident at night. In contrast, Gla-300 showed similar HbA1c reduction to Gla-100, accompanied by lower risk of hypoglycaemia both at night and at any time of day. Gla-300 and IDeg appear more similar than dissimilar, but head-to-head trials are required.

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.02.002
  • Methylprednisolone and greater proteinuria predispose older adults with
           glomerulonephritis to new onset diabetes mellitus
    • Authors: C.C. Lim; M.W.Y. Wong; H.L. Koh; I.Y.J. Mok; Y.M. Chin; J.C.J. Choo
      Abstract: Publication date: Available online 15 February 2018
      Source:Diabetes & Metabolism
      Author(s): C.C. Lim, M.W.Y. Wong, H.L. Koh, I.Y.J. Mok, Y.M. Chin, J.C.J. Choo

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.02.004
  • Risks of diabetic foot syndrome and amputation associated with sodium
           glucose co-transporter 2 inhibitors: A Meta-analysis of Randomized
           Controlled Trials
    • Authors: D. Li; J. Yufeng Yang; T. Wang; S. Shen; H. Tang
      Abstract: Publication date: Available online 13 February 2018
      Source:Diabetes & Metabolism
      Author(s): D. Li, J. Yufeng Yang, T. Wang, S. Shen, H. Tang
      Background The U.S. Food and Drug Administration recently issued a safety communication requiring new warnings of increased leg and foot amputation risk be added to canagliflozin drug labelling. However, the risk associated with other sodium-glucose co-transporter 2 inhibitors (SGLT2i) remains uncertain. Aim This meta-analysis aimed to evaluate the potential risks of diabetic foot syndrome (DFS) and amputation associated with SGLT2i. Methods Relevant databases were searched from inception to June 14, 2017 to identify randomized controlled trials (RCTs) that evaluated risks of DFS and amputation associated with SGLT2i use. A random effects model was performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) using STATA 14. Results Fourteen RCTs involving 26,167 patients were eligible for this meta-analysis. SGLT2i were not significantly associated with increased risk of DFS compared with placebo (OR 1.05, 95% CI: 0.58–1.89). No significant association was observed in the subgroup and sensitivity analysis on DFS risk either. Although SGLT2i, as a class, were not significantly associated with amputation risk (OR 1.40, 95% CI: 0.81–2.41), subgroup analysis showed an increased incidence of amputation in participants using canagliflozin (OR 1.89, 95% CI: 1.37–2.60), compared with oral anti-diabetic drugs and placebo, but not in those using empagliflozin (OR 1.02, 95% CI: 0.71–1.48). Conclusion Current evidence from RCTs suggests that canagliflozin may be positively associated with an increased risk of amputation. Due to limited data, large-scale studies are required to further clarify the association between amputation and individual SGLT2i drugs.

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.02.001
  • High expression of CPT1b in skeletal muscle in metabolically healthy older
    • Authors: C. Bétry; E. Meugnier; M. Pflieger; G. Grenet; S. Hercberg; P. Galan; E. Kesse-Guyot; H. Vidal; M. Laville
      Abstract: Publication date: Available online 12 February 2018
      Source:Diabetes & Metabolism
      Author(s): C. Bétry, E. Meugnier, M. Pflieger, G. Grenet, S. Hercberg, P. Galan, E. Kesse-Guyot, H. Vidal, M. Laville
      Aim Ageing is often associated with metabolic abnormalities such as insulin resistance, although some people remain metabolically healthy throughout their lives. The aim of this study was to gain more insight into metabolic health with increasing age. Methods Two groups of robust and of frail subjects, respectively, were identified based on a composite ageing indicator and recruited from the French SU.VI.MAX 2 cohort of older disease-free subjects. In all, 14 men and 12 women, aged 67±4 years, with similar anthropometric and metabolic characteristics at baseline (BMI: 24.5±2.9kg.m−2) were included in the Compaliclamp study. Skeletal muscle biopsy was performed to assess expression of a set of metabolic and sirtuin (SIRT) genes. Also, whole-body substrate oxidation and insulin sensitivity were determined using the euglycaemic–hyperinsulinaemic clamp and indirect calorimetry techniques. Results Robust subjects were more insulin-sensitive, oxidized more lipid in a fasting state and stored more glucose during the euglycaemic – hyperinsulinaemic clamp than did frail subjects. At the gene-expression level in skeletal muscle, carnitine palmitoyltransferase 1b (CPT1b) messenger RNA (mRNA) levels were around four times higher in the robust compared with frail counterparts. Moreover, both SIRT2 and SIRT6 expression was lower in robust subjects and correlated with CPT1b expression. Conclusion CPT1b overexpression could be helping to maintain metabolic health with increasing age. Thus, it is suggested that targeting CPT1b expression might be an interesting strategy to counteract frailty at an early stage. In addition, future studies should examine the role of sirtuin in CPT1b expression regulation.

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.01.018
  • No prognostic role of a GWAS-derived genetic risk score in renal outcomes
           for patients from French cohorts with type 1 and type 2 diabetes
    • Authors: P. Barbieux; B. György; E. Gand; P.-J. Saulnier; G. Ducrocq; J.-M. Halimi; E. Feigerlova; C. Hulin-Delmotte; P. Llaty; D. Montaigne; V. Rigalleau; R. Roussel; P. Sosner; P. Zaoui; S. Ragot; M. Marre; D.-A. Tregouët; S. Hadjadj
      Abstract: Publication date: Available online 10 February 2018
      Source:Diabetes & Metabolism
      Author(s): P. Barbieux, B. György, E. Gand, P.-J. Saulnier, G. Ducrocq, J.-M. Halimi, E. Feigerlova, C. Hulin-Delmotte, P. Llaty, D. Montaigne, V. Rigalleau, R. Roussel, P. Sosner, P. Zaoui, S. Ragot, M. Marre, D.-A. Tregouët, S. Hadjadj

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.01.016
  • Durability of protective effect of dulaglutide on pancreatic β-cells in
           diabetic mice: GLP-1 receptor expression is not reduced despite long-term
           dulaglutide exposure
    • Authors: T. Kimura; A. Obata; M. Shimoda; H. Hirukawa; Y. Kanda-Kimura; Y. Nogami; K. Kohara; S. Nakanishi; T. Mune; K. Kaku; H. Kaneto
      Abstract: Publication date: Available online 6 February 2018
      Source:Diabetes & Metabolism
      Author(s): T. Kimura, A. Obata, M. Shimoda, H. Hirukawa, Y. Kanda-Kimura, Y. Nogami, K. Kohara, S. Nakanishi, T. Mune, K. Kaku, H. Kaneto
      Aims It is well-known that chronic exposure to large amounts of ligand leads to downregulation of its receptor. It is not known, however, whether a GLP-1R agonist downregulates its receptor. For this reason, our study examined whether GLP-1R expression is reduced after long-term exposure to dulaglutide (Dula) in non-diabetic and diabetic mice. Methods Seven-week-old male db/db and db/m mice were given either Dula (0.6mg/kg×2/week) or a control vehicle (CTL) for 17 weeks. Various metabolic parameters, such as glucose-stimulated insulin secretion (GSIS), insulin and TG content in islets, were evaluated after the intervention. β-cell-related gene expression was also analyzed by real-time RT-PCR. Results In db/m mice, GLP-1R expression in β-cells did not decrease, not even after long-term administration of Dula, compared with control mice, while GLP-1R expression in 24-week-old db/db mice treated with Dula was augmented, rather than downregulated, compared with 24-week-old CTL db/db mice. This was probably due to improved glycaemic control. In db/db mice treated with Dula, food intake and blood glucose levels were significantly decreased up to 24 weeks of age compared with CTL db/db mice, and their expression levels of various β-cell-related genes, insulin content and GSIS were also enhanced. In contrast, oxidative and endoplasmic reticulum stress, inflammation, fibrosis and apoptosis were suppressed with Dula treatment. Conclusion Dula exerts beneficial effects on glycaemic control and has long-lasting protective effects on pancreatic β-cells. GLP-1R expression levels were not reduced at all in non-diabetic as well as diabetic mice despite long-term dulaglutide exposure.

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2017.10.007
  • Efficacy and safety of combination therapy with SGLT2 and DPP4 inhibitors
           in the treatment of type 2 diabetes: A systematic review and meta-analysis
    • Authors: Y.K. Cho; Y.M. Kang; S.E. Lee; J. Lee; J.-Y. Park; W.J. Lee; Y.-J. Kim; C.H. Jung
      Abstract: Publication date: Available online 3 February 2018
      Source:Diabetes & Metabolism
      Author(s): Y.K. Cho, Y.M. Kang, S.E. Lee, J. Lee, J.-Y. Park, W.J. Lee, Y.-J. Kim, C.H. Jung
      Background This review evaluated the efficacy and safety of a combination therapy comprising a sodium-glucose cotransporter type 2 inhibitor (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP4i) in type 2 diabetes. Methods A literature search through to May 2017 was carried out of PubMed, Embase and the Cochrane Central Register of Controlled Trials. Studies were eligible if they were randomized controlled trials (RCTs) comparing SGLT2i plus DPP4i (SGLT2i/DPP4i) against DPP4i±placebo or SGLT2i±placebo and published in English. The primary outcome was change in HbA1c from baseline. Results Eight RCTs comparing SGLT2i/DPP4i and DPP4i, and five RCTs comparing SGLT2i/DPP4i and SGLT2i, with three RCTs involving both comparisons, were included in the present review. SGLT2i/DPP4i resulted in a greater mean HbA1c reduction [weighted mean difference (WMD]): −0.62%] than did DPP4i alone, which was a much less marked reduction (WMD: −0.35%) than with SGLT2i alone. Also, significant differences in body weight loss from baseline were observed only with SGLT2i/DPP4i vs. DPP4i, but not vs. SGLT2i. The risk of hypoglycaemic events was low and similar between treatment groups. When subjects were stratified based on baseline HbA1c, any reduction by SGLT2i/DPP4i in relation to DPP4i was proportional to baseline HbA1c levels. However, compared with SGLT2i, HbA1c reductions with SGLT2i/DPP4i were modest regardless of baseline HbA1c. Conclusion Combination therapy with SGLT2i and DPP4i is both efficacious and safe. In particular, a marked additional glucose-lowering effect is evident when SGLT2i is combined with or added to DPP4i, and not vice versa. However, baseline HbA1c determined the additional glucose-lowering effects of SGLT2i in combined treatment with DPP4i.

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.01.011
  • Relation between HbA1c and incident cardiovascular disease over a period
           of 6 years in the Hong Kong population
    • Authors: E.Y.F. Wan; E.Y.T. Yu; C.S.C. Fung; W.Y. Chin; D.Y.T. Fong; A.K.C. Chan; C.L.K. Lam
      Abstract: Publication date: Available online 3 February 2018
      Source:Diabetes & Metabolism
      Author(s): E.Y.F. Wan, E.Y.T. Yu, C.S.C. Fung, W.Y. Chin, D.Y.T. Fong, A.K.C. Chan, C.L.K. Lam
      Aim The current trend on diabetes management advocates replacing the paradigm from a uniform to an individualized patient-centered haemoglobin A1c (HbA1c) target, but there is no consensus on the optimal HbA1c level. The study aimed at examining the association between HbA1c and the risk of cardiovascular diseases (CVD) for diabetic patients with different characteristics, in order to identify patient-centered treatment targets. Methods A retrospective cohort study was conducted on 115,782 Chinese adult primary care patients with type 2 diabetes mellitus (DM) but no known CVD history, who were prescribed antidiabetic medications in 2010–2011. The cumulative mean HbA1c over a median follow-up period of 5.8 years was used to evaluate the relationship between HbA1c and CVD incidence using Cox analysis. Subgroup analyses were conducted by stratifying different baseline characteristics including gender, age, smoking status, diabetes duration, body mass index, Charlson's comorbidity index and DM treatment modalities. Results For patients with a DM duration of<2years, an exponential relationship between HbA1c and risk of CVD was identified, suggesting that there was no threshold HbA1c level for CVD risk. For other diabetic patients, an HbA1c level of 6.8–7.2% was associated with a minimum risk for CVD and a J-shaped curvilinear association between HbA1c. The risk of CVD increased in patients with HbA1c <6.5% or ≥7.5%. Conclusion Among Chinese primary care patients at the early (<2years) disease stage, lower HbA1c targets (<6.5%) may be warranted to prevent CVD events whilst for all others, excessively lower HbA1c levels may not necessarily better and can potentially be harmful.

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.01.012
  • Association of type 2 diabetes mellitus with self-reported knee pain and
           clinical knee osteoarthritis: The Maastricht Study
    • Authors: J.T.H. Nielen; P.J. Emans; B. van den Bemt; P.C. Dagnelie; M.T. Schram; C.D.A. Stehouwer; N.C. Schaper; K.F.M. Denissen; F. de Vries; A. Boonen
      Abstract: Publication date: Available online 3 February 2018
      Source:Diabetes & Metabolism
      Author(s): J.T.H. Nielen, P.J. Emans, B. van den Bemt, P.C. Dagnelie, M.T. Schram, C.D.A. Stehouwer, N.C. Schaper, K.F.M. Denissen, F. de Vries, A. Boonen

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.01.013
  • Gradual increase in advanced glycation end-products from no diabetes to
           early and regular gestational diabetes: A case-control study
    • Authors: E. Cosson; F. Gary; M.T. Nguyen; L. Bianchi; D. Sandre-Banon; L. Biri; Y. Jaber; C. Cussac-Pillegand; I. Banu; S. Chiheb; L. Carbillon; P. Valensi
      Abstract: Publication date: Available online 3 February 2018
      Source:Diabetes & Metabolism
      Author(s): E. Cosson, F. Gary, M.T. Nguyen, L. Bianchi, D. Sandre-Banon, L. Biri, Y. Jaber, C. Cussac-Pillegand, I. Banu, S. Chiheb, L. Carbillon, P. Valensi

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.01.007
  • Practical management of diabetes patients before, during and after
           surgery: A joint French diabetology and anaesthesiology position statement
    • Authors: E. Cosson; B. Catargi; G. Cheisson; S. Jacqueminet; C. Ichai; A.-M. Leguerrier; A. Ouattara; I. Tauveron; E. Bismuth; D. Benhamou; P. Valensi
      Abstract: Publication date: Available online 3 February 2018
      Source:Diabetes & Metabolism
      Author(s): E. Cosson, B. Catargi, G. Cheisson, S. Jacqueminet, C. Ichai, A.-M. Leguerrier, A. Ouattara, I. Tauveron, E. Bismuth, D. Benhamou, P. Valensi

      PubDate: 2018-03-06T17:07:24Z
      DOI: 10.1016/j.diabet.2018.01.014
  • Morning administration of 0.4U/kg/day insulin glargine 300U/mL provides
           less fluctuating 24-hour pharmacodynamics and more even pharmacokinetic
           profiles compared with insulin degludec 100U/mL in type 1 diabetes
    • Authors: T.S. Bailey; Pettus Roussel Schmider Maroccia Nassr Klein G.B. Bolli
      Abstract: Publication date: Available online 16 November 2017
      Source:Diabetes & Metabolism
      Author(s): T.S. Bailey, J. Pettus, R. Roussel, W. Schmider, M. Maroccia, N. Nassr, O. Klein, G.B. Bolli, R. Dahmen
      Aim To compare steady state pharmacodynamic and pharmacokinetic profiles of insulin glargine 300U/mL (Gla-300) with insulin degludec 100U/mL (Deg-100) in people with type 1 diabetes. Methods This single-centre, randomized, double-blind crossover euglycaemic clamp study included two parallel cohorts with fixed once-daily morning dose regimens. For both insulins participants received 0.4 (n =24) or 0.6U/kg/day (n =24), before breakfast, for 8 days prior to the clamp. The main endpoint was within-day variability (fluctuation) of the smoothed glucose infusion rate (GIR) over 24 hours (GIR-smFL0–24). Results Gla-300 provided 20% less fluctuation of steady state glucose infusion rate profiles than Deg-100 over 24 hours at 0.4U/kg/day (GIR-smFL0–24 treatment ratio 0.80 [90% confidence interval: 0.66 to 0.96], P =0.047), while at the dose of 0.6U/kg/day the difference between insulins was not statistically significant (treatment ratio 0.96 [0.83 to 1.11], P =0.603). Serum insulin concentrations appeared more evenly distributed with both dose levels of Gla-300 versus the same doses of Deg-100, as assessed by relative 6-hour fractions of the area under the curve within 24 hours. Both insulins provided exposure and activity until 30 hours (end of clamp). Conclusion Gla-300 provides less fluctuating steady state pharmacodynamic profiles (i.e. lower within-day variability) and more evenly distributed pharmacokinetic profiles, compared with Deg-100 in a once-daily morning dosing regimen of 0.4U/kg/day.

      PubDate: 2017-12-24T07:28:08Z
  • Pharmacological variability of insulins degludec and glargine 300 U/mL:
           Equivalent or not'
    • Authors: Monnier Colette
      Abstract: Publication date: Available online 14 November 2017
      Source:Diabetes & Metabolism
      Author(s): L. Monnier, C. Colette

      PubDate: 2017-11-18T15:10:00Z
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