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Diabetologia (Online First™)

Screening for gestational diabetes mellitus: cost–utility of different screening strategies based on a woman’s individual risk of disease

Abstract

Aims/hypothesis
The cost-effectiveness of eight strategies for screening for gestational diabetes (including no screening) was estimated with respect to the level of individual patient risk.

Methods
Cost–utility analysis using a decision analytic model populated with efficacy evidence pooled from recent randomised controlled trials, from the funding perspective of the National Health Service in England and Wales. Seven screening strategies using various combinations of screening and diagnostic tests were tested in addition to no screening. The primary outcome measure was the incremental cost per quality-adjusted life-year (QALY) over a lifetime.

Results
The strategy that has the greatest likelihood of being cost-effective is dependent on the risk of gestational diabetes mellitus for each individual woman. When gestational diabetes mellitus risk is <1% then the no screening/treatment strategy is cost-effective; where risk is between 1.0% and 4.2% fasting plasma glucose followed by OGTT is most likely to be cost-effective; and where risk is >4.2%, universal OGTT is most likely to be cost-effective. However, acceptability of the test alters the most cost-effective strategy.

Conclusions/interpretation
Screening for gestational diabetes can be cost-effective. The best strategy is dependent on the underlying risk of each individual and the acceptability of the tests used. The current study suggests that if a woman’s individual risk of gestational diabetes could be accurately predicted, then healthcare resource allocation could be improved by providing an individualised screening strategy.
- Content Type Journal Article
- DOI 10.1007/s00125-010-1881-y
- Authors
  - J. A. Round, Academic Unit of Health Economics, Institute of Health Sciences, University of Leeds, Leeds, UK
  - P. Jacklin, National Collaborating Centre for Women’s and Children’s Health, London, UK
  - R. B. Fraser, Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, UK
  - R. G. Hughes, Simpson Centre for Reproductive Health, The Royal Infirmary of Edinburgh, Edinburgh, UK
  - M. A. Mugglestone, National Collaborating Centre for Women’s and Children’s Health, London, UK
  - R. I. G. Holt, University of Southampton School of Medicine, Southampton, UK
Ageing brain abnormalities in young obese patients with type 2 diabetes: a cause for concern

Ageing brain abnormalities in young obese patients with type 2 diabetes: a cause for concern
- Content Type Journal Article
- DOI 10.1007/s00125-010-1890-x
- Authors
  - J. J. Nolan, Metabolic Research Unit, St James Hospital, Trinity College, Dublin 8, Ireland
From authority recommendations to fact-sheets—a future for guidelines

Abstract
ADA/EASD recommendations and diabetes expert consensus statements are not evidence-based. Reform of guideline development is urgently needed. Overriding governance and composition of the guideline committee is a key problem. Methodologists without important conflicts of interest should lead the development process and have primary responsibility. The rating of the quality of evidence should be separated from making the recommendations, transparency has to be increased and conflicts of interest must be tackled. Patient needs are not yet met in guidelines. Patients increasingly demand concise, easy-to-read summaries of the benefits and risks of medicines together with more comprehensive scientific data. However, patient participation in individual decision making is not considered in guidelines. Guidelines do not provide the information necessary for informed or shared decision making. Study fact-sheets and drug facts boxes should be included in practice guidelines. It is timely to consider patient needs from the outset of the development of future guidelines.
- Content Type Journal Article
- DOI 10.1007/s00125-010-1891-9
- Authors
  - I. Mühlhauser, Unit of Health Sciences and Education, University of Hamburg, Martin-Luther-King Platz 6, 20146 Hamburg, Germany
Biomedical risk factors for decreased cognitive functioning in type 1 diabetes: an 18 year follow-up of the Diabetes Control and Complications Trial (DCCT) cohort

Abstract

Aims/hypothesis
In patients with type 1 diabetes, there has been concern about the effects of recurrent hypoglycaemia and chronic hyperglycaemia on cognitive function. Because other biomedical factors may also increase the risk of cognitive decline, this study examined whether macrovascular risk factors (hypertension, smoking, hypercholesterolaemia, obesity), sub-clinical macrovascular disease (carotid intima–media thickening, coronary calcification) and microvascular complications (retinopathy, nephropathy) were associated with decrements in cognitive function over an extended time period.

Methods
Type 1 diabetes patients (n = 1,144) who had completed a comprehensive cognitive test battery at entry into the Diabetes Control and Complications Trial were re-assessed at a mean of 18.5 (range: 15–23) years later. Univariate and multivariable models examined the relationship between cognitive change and the presence of micro- and macrovascular complications and risk factors.

Results
Univariate modelling showed that smoking history was modestly associated with decrements in learning, memory, spatial information-processing and psychomotor efficiency; hypertension was associated with only psychomotor slowing. Multivariable modelling demonstrated that HbA_1c level, and retinal and renal complications were each independently associated with decrements in psychomotor efficiency. In contrast, no macrovascular risk factors were significant after correcting for multiple comparisons. No interactions were found between these predictors and sex, severe hypoglycaemic events or presence of the APOE ε4 allele.

Conclusions/interpretation
In relatively healthy, middle-aged adults with type 1 diabetes who had been followed for an average of 18.5 years, long-term metabolic control and microvascular factors are independently associated with a decline in cognitive function specifically affecting measures of psychomotor efficiency.

Trial registration
ClinicalTrials.gov NCT00360893

Funding
This study is supported by NIH grant number 5RO1 DK062218-02. The DCCT/EDIC project is supported by contracts with the Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Eye Institute, the National Institute of Neurological Disorders and Stroke, the General Clinical Research Centers Program, the Clinical and Translational Science Awards Program, the National Center for Research Resources and by Genentech through a Cooperative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases.
- Content Type Journal Article
- DOI 10.1007/s00125-010-1883-9
- Authors
  - A. M. Jacobson, Winthrop-University Hospital, Suite 300, 222 Station Plaza North, Mineola, NY 11501, USA
  - C. M. Ryan, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA USA
  - P. A. Cleary, Biostatistics Center, The George Washington University, Rockville, MD USA
  - B. H. Waberski, Biostatistics Center, The George Washington University, Rockville, MD USA
  - K. Weinger, Joslin Diabetes Center/Harvard Medical School, Boston, MA USA
  - G. Musen, Joslin Diabetes Center/Harvard Medical School, Boston, MA USA
  - W. Dahms, Case Western Reserve University, Cleveland, OH USA
  - and the DCCT/EDIC Research Group
Health behaviours, socioeconomic status and diabetes incidence: the Australian Diabetes Obesity and Lifestyle Study (AusDiab)

Abstract

Aims/hypothesis
To identify the impact of socioeconomic status on incident impaired glucose metabolism and type 2 diabetes and to investigate the mediating role of health behaviours on this relationship using national, population-based data.

Methods
The Australian Diabetes Obesity and Lifestyle (AusDiab) Study is a national, population-based, longitudinal study of adults aged 25 years and above. A total sample of 4,405 people provided complete baseline (1999–2000) and 5 year follow-up (2004–2005) data relevant for these analyses. Fasting plasma glucose and 2 h plasma glucose were obtained from an OGTT, and demographic, socioeconomic and behavioural data were collected by interview and questionnaire. Multinomial logistic regression examined the role of socioeconomic position in the development of diabetes and mediation analyses tested the contribution of health behaviours in this relationship.

Results
Highest level of education was a stronger predictor of incident impaired glucose tolerance and type 2 diabetes (p = 0.002), compared with household income (p = 0.103), and occupational grade (p = 0.202). Education remained a significant independent predictor of diabetes in fully adjusted models. However, the relationship was attenuated by the health behaviours (smoking and physical activity). Mediation analyses indicated that these behaviours were partial mediators (explaining 27%) of the socioeconomic status–diabetes relationship.

Conclusion/interpretation
Smoking and physical activity partly mediate the relationship between low education and type 2 diabetes. Identification of these modifiable behavioural mediators should facilitate the development of effective health promotion campaigns to target those at high risk of developing type 2 diabetes.
- Content Type Journal Article
- DOI 10.1007/s00125-010-1888-4
- Authors
  - E. D. Williams, School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, 89 Commercial Road, Melbourne, Victoria 3004, Australia
  - R. J. Tapp, Baker IDI Heart and Diabetes Institute, 75, Commercial Road, Melbourne, Victoria Australia
  - D. J. Magliano, Baker IDI Heart and Diabetes Institute, 75, Commercial Road, Melbourne, Victoria Australia
  - J. E. Shaw, Baker IDI Heart and Diabetes Institute, 75, Commercial Road, Melbourne, Victoria Australia
  - P. Z. Zimmet, Baker IDI Heart and Diabetes Institute, 75, Commercial Road, Melbourne, Victoria Australia
  - B. F. Oldenburg, School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, 89 Commercial Road, Melbourne, Victoria 3004, Australia
Cholesterol toxicity in pancreatic islets from LDL receptor-deficient mice. Reply to: de Souza JC, de Oliveira CAM, Carneiro EM et al. [letter]

Cholesterol toxicity in pancreatic islets from LDL receptor-deficient mice. Reply to: de Souza JC, de Oliveira CAM, Carneiro EM et al. [letter]
- Content Type Journal Article
- DOI 10.1007/s00125-010-1877-7
- Authors
  - J. K. Kruit, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 950 West 28th Ave, Vancouver, BC Canada V5Z 4H4
  - L. R. Brunham, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 950 West 28th Ave, Vancouver, BC Canada V5Z 4H4
  - C. B. Verchere, Child and Family Research Institute, Department of Surgery, University of British Columbia, Vancouver, BC Canada
  - M. R. Hayden, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 950 West 28th Ave, Vancouver, BC Canada V5Z 4H4
Guidelines: we’ll always need them, we sometimes dislike them, and we have to make them better

Guidelines: we’ll always need them, we sometimes dislike them, and we have to make them better
- Content Type Journal Article
- DOI 10.1007/s00125-010-1885-7
- Authors
  - R. Kahn, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
Hypoglycaemia following gastric bypass surgery—diabetes remission in the extreme?

Abstract
Postprandial hypoglycaemia is increasingly recognised as a complication of gastric bypass surgery. While post-bypass hypoglycaemia is often responsive to dietary modification, a subset of individuals develop life-threatening neuroglycopenia, with loss of consciousness, seizures and motor vehicle accidents. Such patients require complex nutritional and medical management strategies to reduce postprandial insulin secretion and stabilise glucose excursions, using medications including acarbose, octreotide and diazoxide, and frequent monitoring of glucose values. In an article in this issue of Diabetologia, nationwide registry data from Sweden were used to assess the frequency of severe hypoglycaemia and potentially related diagnoses (e.g. confusion, syncope, seizures, accidental death) following obesity surgery. Relative risk of hypoglycaemia and related diagnoses were two- to sevenfold higher in the post-gastric bypass population, but absolute risk was small. While these data underscore that hypoglycaemia is an important complication of gastric bypass, many questions regarding frequency, pathogenesis and optimal therapy remain unanswered. Given that hypoglycaemia is usually evaluated in the outpatient setting, more precise assessments of hypoglycaemia frequency will require prospective longitudinal studies in post-bypass cohorts. Until such data are available, practitioners should have a higher awareness of symptoms consistent with neuroglycopenia in patients with a history of bariatric surgery. Understanding the beneficial and challenging metabolic consequences of bariatric surgery is a key imperative for the diabetes community, as such data may yield novel insights into mechanisms by which bariatric surgery can lead to diabetes remission.
- Content Type Journal Article
- DOI 10.1007/s00125-010-1884-8
- Authors
  - M. E. Patti, Research Division, Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
  - A. B. Goldfine, Research Division, Joslin Diabetes Center and Harvard Medical School, 1 Joslin Place, Boston, MA 02215, USA
Posthumous Caesarean section in women with type 1 diabetes mellitus: two cases at one hospital in northern India

Posthumous Caesarean section in women with type 1 diabetes mellitus: two cases at one hospital in northern India
- Content Type Journal Article
- DOI 10.1007/s00125-010-1880-z
- Authors
  - B. Kalra, Bharti Hospital, Karnal, Haryana 132001, India
  - S. Kalra, Bharti Hospital, Karnal, Haryana 132001, India
  - B. Chhabra, Bharti Hospital, Karnal, Haryana 132001, India
Genetic variants affecting incretin sensitivity and incretin secretion

Abstract
Recent genome-wide association studies identified several novel risk genes for type 2 diabetes. The majority of these type 2 diabetes risk variants confer impaired pancreatic beta cell function. Though the molecular mechanisms by which common genetic variation within these loci affects beta cell function are not completely understood, risk variants may alter glucose-stimulated insulin secretion, proinsulin conversion, and incretin signals. In humans, the incretin effect is mediated by the secretion and insulinotropic action of two peptide hormones, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. This review article aims to give an overview of the type 2 diabetes risk loci that were found to associate with incretin secretion or incretin action, paying special attention to the potential underlying mechanisms.
- Content Type Journal Article
- DOI 10.1007/s00125-010-1876-8
- Authors
  - K. Müssig, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University, Member of the German Centre for Diabetes Research (DZD), Otfried-Müller-Strasse 10, 72076 Tübingen, Germany
  - H. Staiger, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University, Member of the German Centre for Diabetes Research (DZD), Otfried-Müller-Strasse 10, 72076 Tübingen, Germany
  - F. Machicao, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University, Member of the German Centre for Diabetes Research (DZD), Otfried-Müller-Strasse 10, 72076 Tübingen, Germany
  - H.-U. Häring, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University, Member of the German Centre for Diabetes Research (DZD), Otfried-Müller-Strasse 10, 72076 Tübingen, Germany
  - A. Fritsche, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University, Member of the German Centre for Diabetes Research (DZD), Otfried-Müller-Strasse 10, 72076 Tübingen, Germany
Multidrug therapy in a patient with Rabson–Mendenhall syndrome

Multidrug therapy in a patient with Rabson–Mendenhall syndrome
- Content Type Journal Article
- DOI 10.1007/s00125-010-1879-5
- Authors
  - Rodrigo O. Moreira, Instituto Estadual de Diabetes e Endocrinologia, Rua Moncorvo Filho 90, Rio de Janeiro, RJ Brazil
  - R. L. Zagury, Instituto Estadual de Diabetes e Endocrinologia, Rua Moncorvo Filho 90, Rio de Janeiro, RJ Brazil
  - T. S. Nascimento, Universidade Presidente Antônio Carlos (FAME, UNIPAC), Juiz de Fora, Brazil
  - L. Zagury, Instituto Estadual de Diabetes e Endocrinologia, Rua Moncorvo Filho 90, Rio de Janeiro, RJ Brazil
Sensor-augmented pump therapy from the diagnosis of childhood type 1 diabetes: results of the Paediatric Onset Study (ONSET) after 12 months of treatment

Abstract

Aims/hypothesis
The value of managing children with type 1 diabetes using a combination of insulin pump and continuous glucose monitoring starting from diagnosis for improving subsequent glycaemic control and preserving residual beta cell function was determined.

Methods
A total of 160 children (aged 1–16 years, mean ± SD: 8.7 ± 4.4 years; 47.5% girls) were randomised to receive insulin pump treatment with continuous glucose monitoring or conventional self-monitoring blood glucose measurements. The primary outcome was the level of HbA_1c after 12 months. Other analyses included fasting C-peptide, glycaemic variability, sensor usage, adverse events, children’s health-related quality of life and parent’s wellbeing.

Results
HbA_1c was not significantly different between the two groups, but patients with regular sensor use had lower values (mean 7.1%, 95% CI 6.8–7.4%) compared with the combined group with no or low sensor usage (mean 7.6%, 95% CI 7.3–7.9%; p = 0.032). At 12 months, glycaemic variability was lower in the sensor group (mean amplitude of glycaemic excursions 80.2 ± 26.2 vs 92.0 ± 33.7; p = 0.037). Higher C-peptide concentrations were seen in sensor-treated 12- to 16-year-old patients (0.25 ± 0.12 nmol/l) compared with those treated with insulin pump alone (0.19 ± 0.07 nmol/l; p = 0.033). Severe hypoglycaemia was reported only in the group without sensors (four episodes).

Conclusion/interpretation
Sensor-augmented pump therapy starting from the diagnosis of type 1 diabetes can be associated with less decline in fasting C-peptide particularly in older children, although regular sensor use is a prerequisite for improved glycaemic control.

Trial registration
ISRCTN.org ISRCTN05450731

Funding
Medtronic International Trading Sàrl, Tolochenaz, Switzerland
- Content Type Journal Article
- DOI 10.1007/s00125-010-1878-6
- Authors
  - O. Kordonouri, Bult Diabetes Centre for Children and Adolescents, Kinderkrankenhaus auf der Bult, Janusz-Korczak-Allee 12, D-30173 Hannover, Germany
  - E. Pankowska, Department of Paediatric Diabetology and Birth Defects, Medical University of Warsaw, Warsaw, Poland
  - B. Rami, Department of Paediatrics, Medical University of Vienna, Vienna, Austria
  - T. Kapellen, Universitätsklinik und Poliklinik für Kinder und Jugendliche, Leipzig, Germany
  - R. Coutant, Département de Pédiatrie, Centre Hospitalier Universitaire, Angers, France
  - R. Hartmann, Bult Diabetes Centre for Children and Adolescents, Kinderkrankenhaus auf der Bult, Janusz-Korczak-Allee 12, D-30173 Hannover, Germany
  - K. Lange, Department of Medical Psychology, Hannover Medical School, Hannover, Germany
  - M. Knip, Hospital for Children and Adolescents and Folkhälsan Research Centre, University of Helsinki, Helsinki, Finland
  - T. Danne, Bult Diabetes Centre for Children and Adolescents, Kinderkrankenhaus auf der Bult, Janusz-Korczak-Allee 12, D-30173 Hannover, Germany
Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis

Abstract

Aims/hypothesis
An earlier meta-analysis showed that diabetes is a risk factor for the development and/or recurrence of depression. Yet whether this risk is different for studies using questionnaires than for those relying on diagnostic criteria for depression has not been examined. This study examined the association of diabetes and the onset of depression by reviewing the literature and conducting a meta-analysis of longitudinal studies on this topic.

Methods
EMBASE, MEDLINE and PsycInfo were searched for articles published up to September 2009. All studies that examined the relationship between type 2 diabetes and the onset of depression were included. Pooled relative risks were calculated using fixed and random effects models.

Results
Eleven studies met our inclusion criteria for this meta-analysis. Based on the pooled data, including 48,808 cases of type 2 diabetes without depression at baseline, the pooled relative risk was 1.24 (95% CI 1.09–1.40) for the random effects model. This risk was significantly higher for studies relying on diagnostic criteria of depression than for studies using questionnaires. However, this difference was no longer significant when controlled for year of publication.

Conclusions/interpretation
Compared with non-diabetic controls, people with type 2 diabetes have a 24% increased risk of developing depression. The mechanisms underlying this relationship are still unclear and warrant further research.
- Content Type Journal Article
- DOI 10.1007/s00125-010-1874-x
- Authors
  - A. Nouwen, School of Psychology, University of Birmingham, Edgbaston, Birmingham, B15 2TT UK
  - K. Winkley, Institute of Psychiatry, Kings College London, London, UK
  - J. Twisk, EMGO+ Institute, VU University Medical Center, Amsterdam, the Netherlands
  - C. E. Lloyd, Faculty of Health and Social Care, The Open University, Milton Keynes, UK
  - M. Peyrot, Department of Sociology, Loyola University Maryland, Baltimore, MD USA
  - K. Ismail, Institute of Psychiatry, Kings College London, London, UK
  - F. Pouwer, CRPS—Center of Research on Psychology in Somatic diseases, Tilburg University, Tilburg, the Netherlands
  - for the European Depression in Diabetes (EDID) Research Consortium
Dysglycaemia and the risk of acute myocardial infarction in multiple ethnic groups: an analysis of 15,780 patients from the INTERHEART study

Abstract

Aims/hypothesis
Although diabetes is an established risk factor for myocardial infarction (MI), disease control may vary. HbA_1c is a reliable index of ambient glucose levels and may provide more information on MI risk than diabetes status.

Methods
The relationship between HbA_1c levels in MI patients and controls who participated in the 52 country INTERHEART study was analysed.

Results
In 15,780 participants with a HbA_1c value (1,993 of whom had diabetes), the mean (SD) levels for HbA_1c were 6.15% (1.10) in the 6,761 MI patients and 5.85% (0.80) in the control participants. After adjustment for age, sex and nine major MI risk factors (including diabetes), higher HbA_1c fifths above the lowest fifth (HbA_1c <5.4%) were associated with progressively higher OR of MI, with OR for the highest HbA_1c fifth (≥6.12%) being 1.55 (95% CI 1.37–1.75). When analysed as a continuous variable after adjustment for the same factors, every 1% higher HbA_1c value was associated with 19% (95% CI 14–23) higher odds of MI, while every 0.5% higher HbA_1c was associated with 9% higher odds of MI (95% CI 7–11). Concordant relationships were noted across subgroups, with a higher OR noted in younger people, patients without diabetes or hypertension, and those from some regions and ethnicities.

Conclusions/interpretation
The HbA_1c value provides more information on MI odds than self-reported diabetes status or many other established risk factors. Every 1% increment independently predicts a 19% higher odds of MI after accounting for other MI risk factors including diabetes.
- Content Type Journal Article
- DOI 10.1007/s00125-010-1871-0
- Authors
  - H. C. Gerstein, The Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON Canada
  - S. Islam, The Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON Canada
  - S. Anand, The Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON Canada
  - W. Almahmeed, Division of Cardiology, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
  - A. Damasceno, Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique
  - A. Dans, Department of Medicine, University of the Philippines College of Medicine, Manila, Philippines
  - C. C. Lang, Division of Medical Sciences, University of Dundee, Dundee, UK
  - M. A. Luna, Department of Medicine, University of Virginia, Charlottesville, VA USA
  - M. McQueen, The Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON Canada
  - S. Rangarajan, The Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON Canada
  - A. Rosengren, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden
  - X. Wang, Laboratory of Human Genetics, Beijing Hypertension League Institute, Beijing, China
  - S. Yusuf, The Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON Canada
A polymorphism in the gene encoding carnosinase (CNDP1) as a predictor of mortality and progression from nephropathy to end-stage renal disease in type 1 diabetes mellitus

Abstract

Aims/hypothesis
Homozygosity for a five leucine repeat (5L–5L) in the carnosinase gene (CNDP1) has been found to be cross-sectionally associated with a low frequency of diabetic nephropathy (DN), mainly in type 2 diabetes. We prospectively investigated in patients with type 1 diabetes whether: (1) 5L–5L is associated with mortality; (2) there is an interaction of 5L–5L with DN or sex for prediction of mortality; and (3) 5L–5L is associated with progression to end-stage renal disease (ESRD).

Methods
In this prospective study in white European patients with type 1 diabetes, individuals with DN were defined by persistent albuminuria ≥300 mg/24 h. Controls without nephropathy were defined by persistent (>15 years) normoalbuminuria <30 mg/24 h. Leucine repeats were assessed with a fluorescent DNA analysis system. Onset of ESRD was defined by need to start chronic dialysis or kidney transplantation.

Results
The study involved 916 patients with DN and 1,170 controls. During follow-up for 8.8 years, 107 patients (14%) with 5L–5L died compared with 182 patients (13.8%) with other genotypes (p = 0.99). There was no significant interaction of 5L–5L with DN for prediction of mortality (p = 0.57), but a trend towards interaction with sex (p = 0.08). In patients with DN, HR for ESRD in 5L–5L vs other genotypes was not constant over time, with increased risk for 5L–5L beyond 8 years of follow-up (p = 0.03).

Conclusions/interpretation
CNDP1 polymorphism was not associated with mortality, and nor was there an interaction of this polymorphism with DN for prediction of mortality in patients with type 1 diabetes. CNDP1 polymorphism predicts progression to ESRD in patients with DN, but only late after baseline measurements.
- Content Type Journal Article
- DOI 10.1007/s00125-010-1863-0
- Authors
  - A. Alkhalaf, Department of Internal Medicine, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
  - S. J. L. Bakker, Department of Internal Medicine, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
  - H. J. G. Bilo, Department of Internal Medicine, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
  - R. O. B. Gans, Department of Internal Medicine, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
  - G. J. Navis, Department of Internal Medicine, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
  - D. Postmus, Department of Epidemiology, University Medical Center Groningen, Groningen, the Netherlands
  - C. Forsblom, Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
  - P. H. Groop, Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
  - N. Vionnet, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche en Santé (UMRS) 937, Pierre and Marie Curie University, Paris, France
  - S. Hadjadj, Department of Endocrinology and Diabetology, Centre Hospitalier Universitaire Poitiers, Poitiers, France
  - M. Marre, Department of Endocrinology, Diabetology and Nutrition, Bichat-Claude Bernard University Hospital, Paris, France
  - H. H. Parving, Department of Medical Endocrinology, University of Copenhagen, Copenhagen, Denmark
  - P. Rossing, Steno Diabetes Center, Gentofte, Denmark
  - L. Tarnow, Steno Diabetes Center, Gentofte, Denmark