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Diabet Med. 2019 Mar;36(3):267-268. doi: 10.1111/dme.13917.

The James Lind Alliance research priorities for diabetes.

Author information

1
Diabetic Medicine, London, UK.
2
Division of Diabetes and Endocrinology, Imperial College, London, UK.
3
Diabetic Medicine, University of Southampton, Southampton, UK.
4
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
PMID:
30770611
DOI:
10.1111/dme.13917
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3.
Diabet Med. 2019 Feb 14. doi: 10.1111/dme.13931. [Epub ahead of print]

Diabetes distress in young adults with early-onset Type 1 diabetes and its prospective relationship with HbA1c and health status.

Author information

1
Institute for Biometrics and Epidemiology, German Diabetes Centre, Leibniz Centre for Diabetes Research, Düsseldorf, Germany.
2
German Centre for Diabetes Research (DZD), Munich-Neuherberg, Germany.
3
Department of Statistics in Medicine, Heinrich Heine University, Düsseldorf, Germany.
4
Medical Psychology Unit, Hannover Medical School, Hannover, Germany.
5
Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany.

Abstract

AIM:

This study aimed to determine cross-sectional relationships between diabetes distress and health-related variables, and prospective associations between diabetes distress and future glycaemic control (HbA1c ) and health status among young adults with early-onset Type 1 diabetes.

METHODS:

Data were collected from a nationwide cohort study of adults whose Type 1 diabetes onset occurred from 0 to 4 years of age during 1993-2002. Questionnaire surveys were conducted in 2012-2013 and 2015-2016 (N = 584). Diabetes distress was assessed via the Problem Areas in Diabetes (PAID) scale (0-100 points), depressive symptoms via the Patient Health Questionnaire-9 (PHQ-9) and health status via the 12-Item Short Form Health Survey (SF-12) questionnaire. Multivariable linear regression analyses were applied to cross-sectional and longitudinal data.

RESULTS:

In the cross-sectional analyses, higher PAID scale total scores (representing higher distress levels) were observed in women than in men and in participants with more severe depressive symptoms. PAID scores were lower in individuals with better physical and mental health. A 1 mmol/mol increase in HbA1c was associated with a 0.28-point increase [95% confidence interval (95% CI) 0.20, 0.36] in diabetes distress. In longitudinal analyses adjusting for age, sex, socio-economic index and HbA1c at baseline, a 10-point higher PAID score at baseline was associated with a 1.82 mmol/mol higher HbA1c level (95% CI 0.43, 3.20) and a 2.48-point lower SF-12 mental health score (95% CI -3.55, -1.42) three years later.

CONCLUSIONS:

The cross-sectional and longitudinal analyses results suggest that diabetes distress impairs health-related outcomes in young adults with early-onset diabetes.

PMID:
30761589
DOI:
10.1111/dme.13931
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4.
Diabetes. 2019 Feb 14. pii: db170926. doi: 10.2337/db17-0926. [Epub ahead of print]

Fenofibrate Rescues Diabetes-Related Impairment of Ischemia-Mediated Angiogenesis by PPARα-Independent Modulation of Thioredoxin Interacting Protein.

Yuan J1,2, Tan JT1,2,3,4, Rajamani K1,2,5, Solly EL3, King EJ1, Lecce L1, Simpson PJ1, Lam YT1,2, Jenkins AJ2,3, Bursill CA1,2,4,5, Keech AC2,3,6, Ng MK7,2,6.

Author information

1
Heart Research Institute, Newtown, NSW, Australia.
2
Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
3
South Australian Health & Medical Research Institute, Adelaide, SA, Australia.
4
Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia.
5
NHMRC Clinical Trial Centre, Camperdown, NSW, Australia.
6
Cardiology Department, Royal Prince Alfred Hospital, NSW, Australia.
7
Heart Research Institute, Newtown, NSW, Australia mkcng@med.usyd.edu.au.

Abstract

Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, reduces lower limb amputations in patients with type 2 diabetes mellitus. The mechanism is, however, unknown. Here we demonstrate that fenofibrate markedly attenuates diabetes-related impairment of ischemia-mediated angiogenesis. In a murine model of hindlimb ischemia, daily oral fenofibrate treatment restored diabetes-impaired blood flow recovery, foot movement, hindlimb capillary density, vessel diameter, and vascular endothelial growth factor (VEGF) signaling to non-diabetic levels in both wildtype and PPARα-knockout mice, indicating that these fenofibrate effects are largely PPARα-independent. In vitro, fenofibric acid (FFA) rescued high glucose (25 mM)-induced impairment of endothelial cell migration, tubulogenesis and survival, in a PPARα-independent manner. Interestingly, fenofibrate in vivo and FFA in vitro reversed high glucose-induced expression of thioredoxin-interacting protein (TXNIP), an exquisitely glucose-inducible gene previously identified as a critical mediator of diabetes-related impairment in neovascularization. Conversely, adenoviral overexpression of TXNIP abrogated the restorative effects of FFA on high glucose-impaired endothelial cell function in vitro, indicating that the effects of FFA are mediated by TXNIP. We conclude that fenofibrate rescues diabetic impairment in ischemia-mediated angiogenesis, in large part, by PPARα-independent regulation of TXNIP. These findings may therefore explain the reduction in amputations seen in diabetic patients treated with fenofibrate.

PMID:
30765336
DOI:
10.2337/db17-0926
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5.
Diabetes. 2019 Feb 14. pii: db180981. doi: 10.2337/db18-0981. [Epub ahead of print]

Glucose Metabolism is Required for Platelet Hyperactivation in a Murine Model of Type 1 Diabetes Mellitus.

Author information

1
Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa.
2
Division of Molecular Medicine, Department of Medicine, Columbia University Medical Center.
3
Molecular Medicine Program, Department of Internal Medicine, University of Utah.
4
GRECC, Department of Internal Medicine, George E. Wahlen VAMC, Salt Lake City, Utah.
5
Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa DRCadmin@uiowa.edu.

Abstract

Patients with type 1 diabetes mellitus (T1DM) have increased thrombosis and platelet activation. The mechanisms for platelet hyperactivation in diabetes are incompletely understood. T1DM is accompanied by hyperglycemia, dyslipidemia, and increased inflammation, in addition to an altered hormonal milieu. In vitro analysis of platelets revealed that normal glucose reduces platelet activation while hyperglycemic conditions increase platelet activation. We therefore hypothesized that hyperglycemia increases platelet glucose utilization, which increases platelet activation to promote thrombosis. Glucose uptake and glycolysis were increased in platelets isolated from mice treated with streptozotocin (STZ), to induce T1DM in concert with induction of glucose transporter 3 (GLUT3). Platelets from STZ-treated mice exhibited increased activation following administration of PAR4 peptide and convulxin. In contrast, platelets isolated from (glucose transporter 1 (GLUT1 and GLUT3) double knockout (DKO) mice, which lack the ability to utilize glucose, failed to increase activation in hyperglycemic mice. Diabetic mice displayed decreased survival in a collagen/epinephrine induced pulmonary embolism model of in vivo platelet activation, relative to non-diabetic controls. Survival following pulmonary embolism was increased in diabetic DKO mice, relative to non-diabetic controls. These data reveal that increased platelet glucose metabolism in vivo, contributes to increased platelet activation and thrombosis in a model of T1DM.

PMID:
30765335
DOI:
10.2337/db18-0981
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7.
Diabetes. 2018 Dec;67(12):2626-2639. doi: 10.2337/db18-0259. Epub 2018 Oct 10.

Syntaxin 4 Expression in Pancreatic β-Cells Promotes Islet Function and Protects Functional β-Cell Mass.

Author information

1
Department of Molecular and Cellular Endocrinology, Diabetes and Metabolism Research Institute of City of Hope, Duarte, CA.
2
Department of Surgery/Division of Transplantation, University of Illinois at Chicago, Chicago, IL.
3
Department of Internal Medicine, Duke Molecular Physiology Institute, Duke University, Durham, NC.
4
Department of Diabetes Immunology, Diabetes and Metabolism Research Institute of City of Hope, Duarte, CA.
5
Department of Molecular and Cellular Endocrinology, Diabetes and Metabolism Research Institute of City of Hope, Duarte, CA dthurmond@coh.org.

Abstract

Syntaxin 4 (Stx4) enrichment in human and mouse islet grafts improves the success of transplants in reversing streptozotocin (STZ)-induced diabetes in mice, although the underlying molecular mechanisms remain elusive. Toward a further understanding of this, human islets and inducible transgenic mice that selectively overexpress Stx4 in islet β-cells (βTG-Stx4) were challenged with proinflammatory stressors in vitro and in vivo. Remarkably, βTG-Stx4 mice resisted the loss of β-cell mass and the glucose intolerance that multiple low doses of STZ induce. Under standard conditions, glucose tolerance was enhanced and mice maintained normal fasting glycemia and insulinemia. Conversely, Stx4 heterozygous knockout mice succumbed rapidly to STZ-induced glucose intolerance compared with their wild-type littermates. Human islet β-cells overexpressing Stx4 exhibited enhanced insulin secretory capability; resilience against proinflammatory cytokine-induced apoptosis; and reduced expression of the CXCL9, CXCL10, and CXCL11 genes coordinate with decreased activation/nuclear localization of nuclear factor-κB. Finding ways to boost Stx4 expression presents a novel potential therapeutic avenue for promoting islet function and preserving β-cell mass.

PMID:
30305365
PMCID:
PMC6245223
[Available on 2019-12-01]
DOI:
10.2337/db18-0259
[Indexed for MEDLINE]
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Diabetes Care. 2019 Apr;42(4):651-656. doi: 10.2337/dc18-0148. Epub 2019 Feb 14.

Diagnostic Accuracy of a Device for the Automated Detection of Diabetic Retinopathy in a Primary Care Setting.

Author information

1
Department of Ophthalmology, VU Medical Center, Amsterdam, the Netherlands f.verbraak@vumc.nl.
2
Department of Ophthalmology and Visual Sciences, University of Iowa Hospital & Clinics, Iowa City, IA.
3
VA Medical Center, Iowa City, IA.
4
IDx, Iowa City, IA.
5
Star-SHL, Rotterdam, the Netherlands.
6
Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands.
7
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
8
Department of Ophthalmology, Radboud University Medical Center, Rotterdam, the Netherlands.
9
Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, the Netherlands.
10
Department of Ophthalmology, Amsterdam Medical Center, Amsterdam, the Netherlands.

Abstract

OBJECTIVE:

To determine the diagnostic accuracy in a real-world primary care setting of a deep learning-enhanced device for automated detection of diabetic retinopathy (DR).

RESEARCH DESIGN AND METHODS:

Retinal images of people with type 2 diabetes visiting a primary care screening program were graded by a hybrid deep learning-enhanced device (IDx-DR-EU-2.1; IDx, Amsterdam, the Netherlands), and its classification of retinopathy (vision-threatening [vt]DR, more than mild [mtm]DR, and mild or more [mom]DR) was compared with a reference standard. This reference standard consisted of grading according to the International Clinical Classification of DR by the Rotterdam Study reading center. We determined the diagnostic accuracy of the hybrid deep learning-enhanced device (IDx-DR-EU-2.1) against the reference standard.

RESULTS:

A total of 1,616 people with type 2 diabetes were imaged. The hybrid deep learning-enhanced device's sensitivity/specificity against the reference standard was, respectively, for vtDR 100% (95% CI 77.1-100)/97.8% (95% CI 96.8-98.5) and for mtmDR 79.4% (95% CI 66.5-87.9)/93.8% (95% CI 92.1-94.9).

CONCLUSIONS:

The hybrid deep learning-enhanced device had high diagnostic accuracy for the detection of both vtDR (although the number of vtDR cases was low) and mtmDR in a primary care setting against an independent reading center. This allows its' safe use in a primary care setting.

PMID:
30765436
DOI:
10.2337/dc18-0148
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Diabetes Care. 2019 Apr;42(4):585-593. doi: 10.2337/dc18-1343. Epub 2019 Feb 14.

Antisense Inhibition of Glucagon Receptor by IONIS-GCGRRx Improves Type 2 Diabetes Without Increase in Hepatic Glycogen Content in Patients With Type 2 Diabetes on Stable Metformin Therapy.

Author information

1
Ionis Pharmaceuticals, Inc., Carlsbad, CA.
2
Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
3
High Field MR Centre, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Vienna, Austria.
4
Ionis Pharmaceuticals, Inc., Carlsbad, CA sbhanot@ionisph.com.

Abstract

OBJECTIVE:

To evaluate the safety and efficacy of IONIS-GCGRRx, a 2'-O-methoxyethyl antisense oligonucleotide targeting the glucagon receptor (GCGR), and the underlying mechanism of liver transaminase increases in patients with type 2 diabetes on stable metformin therapy.

RESEARCH DESIGN AND METHODS:

In three phase 2, randomized, double-blind studies, patients with type 2 diabetes on metformin received weekly subcutaneous injections of IONIS-GCGRRx (50-200 mg) or placebo for 13 or 26 weeks.

RESULTS:

Significant reductions in HbA1c were observed after IONIS-GCGRRx treatment versus placebo at week 14 (-2.0% 200 mg, -1.4% 100 mg, -0.3% placebo; P < 0.001) or week 27 (-1.6% 75 mg, -0.9% 50 mg, -0.2% placebo; P < 0.001). Dose-dependent increases in transaminases were observed with IONIS-GCGRRx, which were attenuated at lower doses and remained mostly within the normal reference range at the 50-mg dose. There were no other significant safety observations and no symptomatic hypoglycemia or clinically relevant changes in blood pressure, LDL cholesterol, or other vital signs. At week 14, IONIS-GCGRRx 100 mg did not significantly affect mean hepatic glycogen content compared with placebo (15.1 vs. -20.2 mmol/L, respectively; P = 0.093) but significantly increased hepatic lipid content (4.2 vs. -2.7%, respectively; P = 0.005) in the presence of transaminase increases.

CONCLUSIONS:

IONIS-GCGRRx is a potent inhibitor of hepatic glucagon receptor expression with a potential to improve glycemic control at low weekly doses in combination with metformin. Significant reductions in HbA1c occurred across the full-dose range tested, with minimal transaminase elevations at lower doses. Furthermore, novel results suggest that despite inhibition of glycogenolysis after GCGR antagonism, IONIS-GCGRRx did not increase hepatic glycogen content.

PMID:
30765435
DOI:
10.2337/dc18-1343
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Diabetes Care. 2019 Apr;42(4):625-634. doi: 10.2337/dc18-1936. Epub 2019 Feb 14.

Occurrence of Diabetic Nephropathy After Renal Transplantation Despite Intensive Glycemic Control: An Observational Cohort Study.

Author information

1
Laboratory of Nephrology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
2
Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
3
Leuven Biostatistics and Statistical Bioinformatics Centre, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium.
4
Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
5
Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
6
Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
7
Department of Diabetes and Endocrinology, University Hospitals Leuven, Leuven, Belgium.
8
Histocompatibility and Immunogenetic Laboratory, Red Cross Flanders, Mechelen, Belgium.
9
Laboratory of Nephrology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium maarten.naesens@uzleuven.be.

Abstract

OBJECTIVE:

The kinetics and risk factors of diabetic nephropathy after kidney transplantation remain unclear. This study investigated the posttransplant occurrence of diabetic nephropathy and the contribution of posttransplant glycemic control.

RESEARCH DESIGN AND METHODS:

We performed a single-center prospective cohort study of 953 renal allograft recipients and 3,458 protocol-specified renal allograft biopsy specimens up to 5 years after transplantation. The effects of pretransplant diabetes and glycemic control (glycated hemoglobin levels) on the posttransplant histology were studied.

RESULTS:

Before transplantation, diabetes was present in 164 (17.2%) renal allograft recipients, primarily type 2 (n = 146 [89.0%]). Despite intensive glycemic control (glycated hemoglobin 7.00 ± 1.34% [53 ± 14.6 mmol/mol], 6.90 ± 1.22% [52 ± 13.3 mmol/mol], and 7.10 ± 1.13% [54 ± 12.4 mmol/mol], at 1, 2, and 5 years after transplantation), mesangial matrix expansion reached a cumulative incidence of 47.7% by 5 years in the pretransplant diabetes group versus 27.1% in patients without diabetes, corresponding to a hazard ratio of 1.55 (95% CI 1.07-2.26; P = 0.005). Mesangial matrix expansion was not specific for diabetic nephropathy and associated independently with increasing age. Pretransplant diabetes was associated with posttransplant proteinuria but not with estimated glomerular filtration rate, graft failure, or any other structural changes of the glomerular, vascular, or tubulointerstitial renal compartments. The occurrence of diabetic nephropathy was independent of posttransplant glycated hemoglobin levels.

CONCLUSIONS:

Mesangial matrix expansion, an early indicator of diabetic nephropathy, can occur rapidly in patients with diabetes before transplantation, despite intensive glycemic control. Prevention of diabetic nephropathy requires more than pursuing low levels of glycated hemoglobin.

PMID:
30765434
DOI:
10.2337/dc18-1936
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Diabetes Care. 2019 Feb 14. pii: dc182201. doi: 10.2337/dc18-2201. [Epub ahead of print]

Effect of a Behavioral Weight Loss Intervention in People With Serious Mental Illness and Diabetes.

Author information

1
Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD etseng3@jhmi.edu.
2
Welch Center for Prevention, Epidemiology, and Clinical Research, The Johns Hopkins University, Baltimore, MD.
3
Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD.
4
Towson University, Baltimore, MD.
5
Department of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
6
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD.
7
Department of Mental Health, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
8
Department of Biostatistics, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.

Abstract

OBJECTIVE:

Given the high prevalence of obesity and diabetes in patients with serious mental illness (SMI) and the lack of evidence on the effects of weight loss programs in SMI patients with diabetes, we evaluated the effectiveness of a behavioral weight loss intervention among SMI participants with and without diabetes.

RESEARCH DESIGN AND METHODS:

Using data from ACHIEVE, a randomized controlled trial to evaluate the effects of a behavioral weight loss intervention among overweight/obese people with SMI, we assessed and compared weight change from baseline to 18 months in participants with and without diabetes using a longitudinal mixed-effects model.

RESULTS:

Of the 291 trial participants, 82 (28.2%) participants had diabetes (34 and 48 in intervention and control groups, respectively) at baseline. Participants with diabetes were more likely to be taking antipsychotics (31.7% vs. 18.7%, P = 0.02). At 18 months, participants in the control group with diabetes lost 1.2 lb (0.6%) of body weight compared with 0.8 lb (0.7%) among those without diabetes. In the intervention group, participants with diabetes lost 13.7 lb (6.6%) of their initial body weight compared with 5.4 lb (2.9%) for those without diabetes. Corresponding net effects (intervention minus control) were 4.6 lb (2.2%) and 12.5 lb (6.0%) net weight reduction over 18 months in the no diabetes and the diabetes subgroups, respectively. However, the between-group difference in intervention effects was statistically nonsignificant (absolute weight change: P-interaction = 0.08; % weight change: P-interaction = 0.10).

CONCLUSIONS:

A behavioral weight loss intervention is effective among overweight and obese individuals with SMI regardless of their diabetes status.

PMID:
30765433
DOI:
10.2337/dc18-2201
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Diabetes Care. 2019 Apr;42(4):514-519. doi: 10.2337/dc18-1471. Epub 2019 Feb 14.

Overall Quality of Care Predicts the Variability of Key Risk Factors for Complications in Type 2 Diabetes: An Observational, Longitudinal Retrospective Study.

Author information

1
Insititut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain aceriell@clinic.cat.
2
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
3
Department of Cardiovascular and Metabolic Diseases, IRCCS MultiMedica, Sesto San Giovanni, Milan, Italy.
4
Center for Outcomes Research and Clinical Epidemiology (CORESEARCH), Pescara, Italy.
5
Department of Medical Sciences, Scientific Institute "Casa Sollievo della Sofferenza," San Giovanni Rotondo, Foggia, Italy.
6
Department of Cardionephrology, IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genoa, Italy.
7
Department of Medicine, University of Padua, Padua, Italy.
8
Diabetes and Metabolism Unit, Department of Internal Medicine, ASL Turin 5, Chieri, Turin, Italy.
9
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Abstract

OBJECTIVE:

An association between variability in clinical parameters (HbA1c, blood pressure, cholesterol, and uric acid) and risk of complications in type 2 diabetes has been reported. In this analysis, we investigated to what extent such variability is associated with overall quality of care.

RESEARCH DESIGN AND METHODS:

The quality of care summary score (Q-score) represents a validated, overall quality of care indicator ranging between 0 and 40; the higher the score, the better the quality of care provided by the diabetes center. We identified patients with five or more measurements of clinical parameters after the assessment of the Q-score. Multiple linear regression analyses assessed the role of the Q-score in predicting the variability of the different parameters.

RESULTS:

Overall, 273,888 patients were analyzed. The variability of all the parameters systematically increased with decreasing Q-score values. At multivariate linear regression analysis, compared with a Q-score >25, a score <15 was associated with a significantly larger variation in HbA1c, blood pressure, uric acid, total cholesterol, and LDL cholesterol and a lower variation in HDL cholesterol. The analysis of standardized β coefficients show that the Q-score has a larger impact on the variability of HbA1c (0.34; P < 0.0001), systolic blood pressure (0.21; P < 0.0001), total cholesterol (0.21; P < 0.0001), and LDL cholesterol (0.20; P < 0.0001).

CONCLUSIONS:

The variability of risk factors for diabetic complications is associated with quality of care. Quality of care improvement initiatives should be targeted to increase the achievement of the recommended target while reducing such variability.

PMID:
30765432
DOI:
10.2337/dc18-1471
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Diabetes Care. 2019 Feb 14. pii: dc181426. doi: 10.2337/dc18-1426. [Epub ahead of print]

Diabetes Distress, Intentional Hyperglycemia at Work, and Glycemic Control Among Workers With Type 1 Diabetes.

Author information

1
Diabetes Management Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark.
2
National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.
3
Department of Psychology, University of Copenhagen, Copenhagen, Denmark.
4
Diabetes Management Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark ingrid.willaing.tapager@regionh.dk.

Abstract

OBJECTIVE:

The aim was to explore relationships between work-related factors, work-related diabetes distress (WRDD), diabetes distress (measured by Problem Areas in Diabetes [PAID]-5 scale), intentional hyperglycemia at work (IHW), and glycemic control.

RESEARCH DESIGN AND METHODS:

A cross-sectional survey was conducted with 1,030 working adults with type 1 diabetes and linked with electronic health record data from a specialist diabetes clinic in Denmark. With use of structural equation modeling, two alternative models were compared, based on fit indices, statistical significance, and theoretical meaningfulness.

RESULTS:

A combined model provided the best fit to the data. WRDD was more strongly affected by work ability, opportunity to self-manage at work, being treated differently, and job demands. PAID-5 was more strongly affected by identity concern and blame and judgment. Both PAID-5 and WRDD were associated with more frequent IHW, which was associated in turn with worse glycemic control.

CONCLUSIONS:

Work-related factors are associated with WRDD and PAID-5. Distress increases the frequency of IHW, which is, in turn, associated with worse glycemic control. Future studies should investigate ways to balance diabetes management and work life without compromising diabetes care.

PMID:
30765430
DOI:
10.2337/dc18-1426
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Diabetes Care. 2019 Apr;42(4):520-528. doi: 10.2337/dc18-2156. Epub 2019 Feb 14.

Comparative Effects of Proximal and Distal Small Intestinal Glucose Exposure on Glycemia, Incretin Hormone Secretion, and the Incretin Effect in Health and Type 2 Diabetes.

Author information

1
Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia.
2
Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
3
Nutrition and Metabolism, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
4
Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
5
Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia tongzhi.wu@adelaide.edu.au.
6
Institute of Diabetes, School of Medicine, Southeast University, Nanjing, Jiangsu, China.

Abstract

OBJECTIVE:

Cells releasing glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are distributed predominately in the proximal and distal gut, respectively. Hence, the region of gut exposed to nutrients may influence GIP and GLP-1 secretion and impact on the incretin effect and gastrointestinal-mediated glucose disposal (GIGD). We evaluated glycemic and incretin responses to glucose administered into the proximal or distal small intestine and quantified the corresponding incretin effect and GIGD in health and type 2 diabetes mellitus (T2DM).

RESEARCH DESIGN AND METHODS:

Ten healthy subjects and 10 patients with T2DM were each studied on four occasions. On two days, a transnasal catheter was positioned with infusion ports opening 13 cm and 190 cm beyond the pylorus, and 30 g glucose with 3 g 3-O-methylglucose (a marker of glucose absorption) was infused into either site and 0.9% saline into the alternate site over 60 min. Matching intravenous isoglycemic clamp studies were performed on the other two days. Blood glucose, serum 3-O-methylglucose, and plasma hormones were evaluated over 180 min.

RESULTS:

In both groups, blood glucose and serum 3-O-methylglucose concentrations were higher after proximal than distal glucose infusion (all P < 0.001). Plasma GLP-1 increased minimally after proximal, but substantially after distal, glucose infusion, whereas GIP increased promptly after both infusions, with concentrations initially greater, but less sustained, with proximal versus distal infusion (all P < 0.001). Both the incretin effect and GIGD were less with proximal than distal glucose infusion (both P ≤ 0.009).

CONCLUSIONS:

The distal, as opposed to proximal, small intestine is superior in modulating postprandial glucose metabolism in both health and T2DM.

PMID:
30765429
DOI:
10.2337/dc18-2156
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Diabetes Care. 2019 Feb 14. pii: dc182212. doi: 10.2337/dc18-2212. [Epub ahead of print]

Suboptimal Nocturnal Glucose Control Is Associated With Large for Gestational Age in Treated Gestational Diabetes Mellitus.

Author information

1
School of Health and Social Care, University of Lincoln, Lincoln, U.K.
2
Division of Clinical and Population Sciences, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, U.K.
3
Leeds Teaching Hospitals NHS Trust, Leeds, U.K.
4
York NHS Foundation Trust, York, U.K.
5
Division of Maternal Health, St Thomas' Hospital, King's College London, London, U.K.
6
Division of Clinical and Population Sciences, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, U.K. e.m.scott@leeds.ac.uk.

Abstract

OBJECTIVE:

Continuous glucose monitoring (CGM) provides far greater detail about fetal exposure to maternal glucose across the 24-h day. Our aim was to examine the role of temporal glucose variation on the development of large for gestational age (LGA) infants in women with treated gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS:

We performed a prospective observational study of 162 pregnant women with GDM in specialist multidisciplinary antenatal diabetes clinics. Participants undertook 7-day masked CGM at 30-32 weeks' gestation. Standard summary indices and glycemic variability measures of CGM were calculated. Functional data analysis was applied to determine differences in temporal glucose profiles. LGA was defined as birth weight ≥90th percentile adjusted for infant sex, gestational age, maternal BMI, ethnicity, and parity.

RESULTS:

Mean glucose was significantly higher in women who delivered an LGA infant (6.2 vs. 5.8 mmol/L, P = 0.025, or 111.6 mg/dL vs. 104.4 mg/dL). There were no significant differences in percentage time in, above, or below the target glucose range or in glucose variability measures (all P > 0.05). Functional data analysis revealed that the higher mean glucose was driven by a significantly higher glucose for 6 h overnight (0030-0630 h) in mothers of LGA infants (6.0 ± 1.0 mmol/L vs. 5.5 ± 0.8 mmol/L, P = 0.005, and 108.0 ± 18.0 mg/dL vs. 99.0 ± 14.4 mg/dL).

CONCLUSIONS:

Mothers of LGA infants run significantly higher glucose overnight compared with mothers without LGA. Detecting and addressing nocturnal glucose control may help to further reduce rates of LGA in women with GDM.

PMID:
30765428
DOI:
10.2337/dc18-2212
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16.
Diabetes Care. 2019 Feb 10. pii: dc181953. doi: 10.2337/dc18-1953. [Epub ahead of print]

Seasonal Variations in the Achievement of Guideline Targets for HbA1c, Blood Pressure, and Cholesterol Among Patients With Type 2 Diabetes: A Nationwide Population-Based Study (ABC Study JDDM49).

Author information

1
Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan m-sakamoto@umin.ac.jp.
2
Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
3
Department of Cardiology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
4
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
5
Department of Cardiology, Tsuruoka Kyoritsu Hospital, Tsuruoka-shi, Yamagata, Japan.
6
Department of Pathology, Tsuruoka Kyoritsu Hospital, Tsuruoka-shi, Yamagata, Japan.
7
Clinical Research Support Center, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.

Abstract

OBJECTIVE:

Precise monthly achievement rates for reaching guideline targets for HbA1c, blood pressure (BP), and lipid levels remain unknown. We evaluated achievement rates on a monthly basis in persons with type 2 diabetes mellitus (T2DM) and explored related factors.

RESEARCH DESIGN AND METHODS:

This retrospective study initially analyzed data on 104,601 persons with T2DM throughout Japan. Patients whose HbA1c, BP, and LDL cholesterol were measured ≥12 times during a 24-month period were included. We evaluated monthly achievement rates. Achieved targets were defined as HbA1c <7%, BP <130/80 mmHg, and LDL cholesterol <100 mg/dL. Achievement of all targets was expressed as the "all ABC achievement."

RESULTS:

A total of 4,678 patients were analyzed. The achievement rates of all ABC, HbA1c, BP, and LDL cholesterol were lowest in winter, with those for systolic BP (SBP) being particularly low (all ABC, summer 15.6%, winter 9.6%; HbA1c, 53.1%, 48.9%; SBP, 56.6%, 40.9%; LDL cholesterol, 50.8%, 47.2%). In winter, age ≥65 years (odds ratio 0.47 [95% CI 0.34-0.63]) was independently related to decreased achievement rates for SBP, BMI ≥25 kg/m2 (BMI 25-30 kg/m2 0.45 [0.29-0.70]; BMI ≥30 kg/m2 0.35 [0.22-0.57]), and diabetes duration ≥10 years (0.53 [0.37-0.76]) were independently related to lower achievement rates for HbA1c. Insulin use and sulfonylurea use were independently associated with the decreased all ABC achievement rates in both summer and winter.

CONCLUSIONS:

The all ABC achievement rate for guideline targets changed on a monthly basis. Seasonal variations in the all ABC achievement rate should be considered when managing T2DM in ordinary clinical practices.

PMID:
30739885
DOI:
10.2337/dc18-1953
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17.
Diabetes Care. 2018 Nov;41(11):2265-2274. doi: 10.2337/dc18-1150.

Clinical Implications of Real-time and Intermittently Scanned Continuous Glucose Monitoring.

Author information

1
University of California, San Diego, and Taking Control of Your Diabetes, San Diego, CA sedelman@ucsd.edu.
2
Maryland Endocrine, Columbia, MD.
3
Clinical and Translational Research Institute and University of California, San Diego, San Diego, CA.
4
University of Washington, Seattle, WA.

Abstract

Two types of continuous glucose monitoring (CGM) systems are now available: real-time CGM (rtCGM) and intermittently scanned (isCGM). Current rtCGM systems automatically transmit a continuous stream of glucose data to the user, provide alerts and active alarms, and transmit glucose data (trend and numerical) in real time to a receiver, smart watch, or smartphone. The current isCGM system provides the same type of glucose data but requires the user to purposely scan the sensor to obtain information, and it does not have alerts and alarms. Both CGM technologies have significant advantages over self-monitoring of blood glucose; however, differences in the features and capabilities of the two approaches must be considered when guiding patient selection of the system that meets their individual needs.

PMID:
30348844
DOI:
10.2337/dc18-1150
[Indexed for MEDLINE]
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18.
Diabetes Care. 2018 Nov;41(11):2275-2280. doi: 10.2337/dc18-1581. Epub 2018 Sep 17.

Glucose Management Indicator (GMI): A New Term for Estimating A1C From Continuous Glucose Monitoring.

Author information

1
International Diabetes Center Park Nicollet, Minneapolis, MN richard.bergenstal@parknicollet.com.
2
Jaeb Center for Health Research, Tampa, FL.
3
The diaTribe Foundation, San Francisco, CA.
4
Grunberger Diabetes Institute, Bloomfield Hills, MI.
5
National Institutes of Health, Bethesda, MD.
6
JDRF, New York, NY.
7
Close Concerns, San Francisco, CA.
8
Science Consulting in Diabetes, Neuss, Germany.
9
Northwestern University Feinberg School of Medicine, Chicago, IL.
10
Sacred Heart and Providence Health Systems, Pensacola, FL.
11
American Diabetes Association, Arlington, VA.

Abstract

While A1C is well established as an important risk marker for diabetes complications, with the increasing use of continuous glucose monitoring (CGM) to help facilitate safe and effective diabetes management, it is important to understand how CGM metrics, such as mean glucose, and A1C correlate. Estimated A1C (eA1C) is a measure converting the mean glucose from CGM or self-monitored blood glucose readings, using a formula derived from glucose readings from a population of individuals, into an estimate of a simultaneously measured laboratory A1C. Many patients and clinicians find the eA1C to be a helpful educational tool, but others are often confused or even frustrated if the eA1C and laboratory-measured A1C do not agree. In the U.S., the Food and Drug Administration determined that the nomenclature of eA1C needed to change. This led the authors to work toward a multipart solution to facilitate the retention of such a metric, which includes renaming the eA1C the glucose management indicator (GMI) and generating a new formula for converting CGM-derived mean glucose to GMI based on recent clinical trials using the most accurate CGM systems available. The final aspect of ensuring a smooth transition from the old eA1C to the new GMI is providing new CGM analyses and explanations to further understand how to interpret GMI and use it most effectively in clinical practice. This Perspective will address why a new name for eA1C was needed, why GMI was selected as the new name, how GMI is calculated, and how to understand and explain GMI if one chooses to use GMI as a tool in diabetes education or management.

PMID:
30224348
PMCID:
PMC6196826
[Available on 2019-11-01]
DOI:
10.2337/dc18-1581
[Indexed for MEDLINE]
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19.
Diabetes Care. 2018 Nov;41(11):2414-2420. doi: 10.2337/dc18-0718. Epub 2018 Sep 13.

Association of Albuminuria With Intraglomerular Hydrostatic Pressure and Insulin Resistance in Subjects With Impaired Fasting Glucose and/or Impaired Glucose Tolerance.

Author information

1
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan naranotsudadesu@infoseek.jp.
2
Department of Nephrology, Osaka City University Graduate School of Medicine, Osaka, Japan.
3
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
4
Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Abstract

OBJECTIVE:

Little is known about the relationships between insulin resistance, intrarenal hemodynamics, and urinary albumin excretion (UAE) in humans with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). The aim of the current study was to examine intrarenal hemodynamic abnormalities, insulin resistance, and UAE in subjects with IFG or IGT. We hypothesized that intrarenal hemodynamic abnormalities would be associated with insulin resistance.

RESEARCH DESIGN AND METHODS:

Fifty-four kidney donors underwent 75-g oral glucose tolerance and inulin and para-aminohippuric acid clearance testing. Insulin sensitivity index (ISI) was evaluated by the Matsuda index. Intrarenal hemodynamic parameters were calculated by the Gomez formulae.

RESULTS:

Of the 54 subjects, 33 exhibited IFG or IGT and 31 exhibited normal glucose tolerance (NGT). Glomerular hydrostatic pressure (Pglo) and UAE were significantly higher in the IFG or IGT subjects with obesity (P = 0.015 and 0.0001, respectively). Log ISI correlated significantly and negatively with Pglo (r = -0.351, P = 0.009) in all subjects. In multiple regression analyses among all subjects, log ISI was associated significantly and independently with Pglo (β = -0.316, P = 0.015), after adjustment for age, sex, and systolic blood pressure. Further, BMI (β = 0.517, P = 0.0004), Pglo (β = 0.420, P = 0.004), and log ISI (β = -0.366, P = 0.008) were each associated significantly and independently with UAE after adjustment.

CONCLUSIONS:

We demonstrated that increased insulin resistance is associated with increased Pglo and UAE in IFG or IGT subjects. These hemodynamic burdens and insulin resistance may cause injury to the glomeruli even in subjects with IFG or IGT.

PMID:
30217931
DOI:
10.2337/dc18-0718
[Indexed for MEDLINE]
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20.
Lancet. 2018 Nov 24;392(10161):2239-2240. doi: 10.1016/S0140-6736(18)32460-7. Epub 2018 Oct 4.

Lorcaserin: balancing efficacy with potential risks.

Author information

1
Metabolic Research Laboratory, Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, University of Navarra, IdiSNA, CIBEROBN, 31008 Pamplona, Spain.
2
Metabolic Research Laboratory, Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, University of Navarra, IdiSNA, CIBEROBN, 31008 Pamplona, Spain. Electronic address: gfruhbeck@unav.es.
PMID:
30293772
DOI:
10.1016/S0140-6736(18)32460-7
[Indexed for MEDLINE]
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