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Brock C, Andersen H, Alibegovic AC, Andersen ST, Andreasen LJ, Charles MH, Christensen DH, Drewes AM, Gall MA, Gylfadottir SS, Hansen CS, Hecquet SK, Jensen TS, Karlsson P, Knudsen LB, Lobato CB, Kufaishi H, Maalmi H, Mizrak HI, Nilsen KB, Perkins BA, Røikjer J, Rossing P, Rungby J, Rømer J, Stouge A, Sulek K, Søfteland E, Tahrani AA, Terkelsen AJ, Tesfaye S, Wegeberg A, Åkerström T, Brock B, Pop-Busui R. Barriers and new opportunities in developing effective therapies for diabetic neuropathy: International expert consensus recommendations. Diabetes Res Clin Pract 2025; 221:112010. [PMID: 39855602 DOI: 10.1016/j.diabres.2025.112010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 01/08/2025] [Accepted: 01/19/2025] [Indexed: 01/27/2025]
Abstract
BACKGROUND Diabetic neuropathy (DN) affects up to half of individuals with type 1 and type 2 diabetes. Despite evidence that improving metabolic and cardiovascular health can slow its progression, DN remains a significant clinical challenge due to the lack of disease-modifying therapies and effective pain management strategies. This consensus aimed to identify gaps and recommend strategies to address these challenges. METHOD A workshop, initiated by Steno Diabetes Centre Copenhagen and the Danish Diabetes and Endocrinology Academy, conducted a gap analysis based on insights from clinical studies, observational cohorts, and clinical practice. Online invitations targeted experienced clinicians, researchers, and drug developers committed to improving DN treatment through innovative clinical trials. Thirty-five participants from six countries reached consensus via a Delphi process on key steps to advance DN therapy. RESULT Four critical barriers and needs were addressed: (1) Translating bench research to clinical practice, (2) Enhancing clinical trial design, (3) Improving outcome measures, and (4) Identifying effective treatments for painful DN. CONCLUSION Successful interventional trials require robust outcome measures to capture clinically meaningful changes in DN phenotypes, providing the basis for developing effective, disease-modifying treatments.
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Affiliation(s)
- C Brock
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark; Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - H Andersen
- Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
| | - A C Alibegovic
- Clinical Development and Project Leadership, Novo Nordisk A/S, Søborg, Denmark
| | - S T Andersen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | | | - M H Charles
- Steno Diabetes Center Aarhus, Aarhus, Denmark
| | - D H Christensen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Epidemiology, Aarhus University Hospital, Denmark
| | - A M Drewes
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark; Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - M-A Gall
- Clinical Development and Project Leadership, Novo Nordisk A/S, Søborg, Denmark
| | - S S Gylfadottir
- Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; Danish Pain Research Center, Health Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - C S Hansen
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - S K Hecquet
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - T S Jensen
- Danish Pain Research Center, Health Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - P Karlsson
- Danish Pain Research Center, Health Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Core Centre for Molecular Morphology, Section for Stereology for Microscopy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - L B Knudsen
- Chief Scientific Advisor Office, Research & Early Development, Novo Nordisk A/S, Denmark
| | - C B Lobato
- Section of Endocrinology, Department of Medicine, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - H Kufaishi
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - H Maalmi
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - H I Mizrak
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - K B Nilsen
- Section for Clinical Neurophysiology, Department of Neurology, Oslo University Hospital, Oslo, Norway
| | - B A Perkins
- Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - J Røikjer
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark
| | - P Rossing
- Steno Diabetes Center Copenhagen, Herlev, Denmark and Department of Clinical Medicine, University of Copenhagen, Denmark
| | - J Rungby
- Steno Diabetes Center Copenhagen, Herlev, Denmark and Department of Clinical Medicine, University of Copenhagen, Denmark
| | - J Rømer
- Clinical Development and Project Leadership, Novo Nordisk A/S, Søborg, Denmark
| | - A Stouge
- Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
| | - K Sulek
- Steno Diabetes Center Copenhagen, Herlev, Denmark and Department of Clinical Medicine, University of Copenhagen, Denmark
| | - E Søfteland
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - A A Tahrani
- Clinical Development and Project Leadership, Novo Nordisk A/S, Søborg, Denmark; University of Birmingham, Department of Metabolism and Systems Science, Birmingham, UK
| | - A J Terkelsen
- Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - S Tesfaye
- Diabetes Research Unit, Sheffield Teaching Hospitals and the University of Sheffield, Sheffield, UK
| | - A Wegeberg
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - T Åkerström
- Diabetes Pharmacology, Novo Nordisk A/S, Denmark
| | - B Brock
- University of Birmingham, Department of Metabolism and Systems Science, Birmingham, UK.
| | - R Pop-Busui
- Department of Medicine, Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health & Science University, Portland USA
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Khalil MAM, Sadagah NM, Tan J, Syed FO, Chong VH, Al-Qurashi SH. Pros and cons of live kidney donation in prediabetics: A critical review and way forward. World J Transplant 2024; 14:89822. [PMID: 38576756 PMCID: PMC10989475 DOI: 10.5500/wjt.v14.i1.89822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 12/11/2023] [Accepted: 01/16/2024] [Indexed: 03/15/2024] Open
Abstract
There is shortage of organs, including kidneys, worldwide. Along with deceased kidney transplantation, there is a significant rise in live kidney donation. The prevalence of prediabetes (PD), including impaired fasting glucose and impaired glucose tolerance, is on the rise across the globe. Transplant teams frequently come across prediabetic kidney donors for evaluation. Prediabetics are at risk of diabetes, chronic kidney disease, cardiovascular events, stroke, neuropathy, retinopathy, dementia, depression and nonalcoholic liver disease along with increased risk of all-cause mortality. Unfortunately, most of the studies done in prediabetic kidney donors are retrospective in nature and have a short follow up period. There is lack of prospective long-term studies to know about the real risk of complications after donation. Furthermore, there are variations in recommendations from various guidelines across the globe for donations in prediabetics, leading to more confusion among clinicians. This increases the responsibility of transplant teams to take appropriate decisions in the best interest of both donors and recipients. This review focuses on pathophysiological changes of PD in kidneys, potential complications of PD, other risk factors for development of type 2 diabetes, a review of guidelines for kidney donation, the potential role of diabetes risk score and calculator in kidney donors and the way forward for the evaluation and selection of prediabetic kidney donors.
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Affiliation(s)
- Muhammad Abdul Mabood Khalil
- Center of Renal Diseases and Transplantation, King Fahad Armed Forces Hospital Jeddah, Jeddah 23311, Saudi Arabia
| | - Nihal Mohammed Sadagah
- Center of Renal Diseases and Transplantation, King Fahad Armed Forces Hospital Jeddah, Jeddah 23311, Saudi Arabia
| | - Jackson Tan
- Department of Nephrology, RIPAS Hospital Brunei Darussalam, Brunei Muara BA1710, Brunei Darussalam
| | - Furrukh Omair Syed
- Center of Renal Diseases and Transplantation, King Fahad Armed Forces Hospital Jeddah, Jeddah 23311, Saudi Arabia
| | - Vui Heng Chong
- Division of Gastroenterology and Hepatology, Department of Medicine, Raja Isteri Pengiran Anak Saleha Hospital, Bandar Seri Begawan BA1710, Brunei Darussalam
| | - Salem H Al-Qurashi
- Center of Renal Diseases and Transplantation, King Fahad Armed Forces Hospital Jeddah, Jeddah 23311, Saudi Arabia
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Spallone V. Diabetic neuropathy: Current issues in diagnosis and prevention. CHRONIC COMPLICATIONS OF DIABETES MELLITUS 2024:117-163. [DOI: 10.1016/b978-0-323-88426-6.00016-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Zhou J, Zhou S, Fan P, Li X, Ying Y, Ping J, Pan Y. Implantable Electrochemical Microsensors for In Vivo Monitoring of Animal Physiological Information. NANO-MICRO LETTERS 2023; 16:49. [PMID: 38087121 PMCID: PMC10716106 DOI: 10.1007/s40820-023-01274-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Accepted: 10/24/2023] [Indexed: 10/11/2024]
Abstract
In vivo monitoring of animal physiological information plays a crucial role in promptly alerting humans to potential diseases in animals and aiding in the exploration of mechanisms underlying human diseases. Currently, implantable electrochemical microsensors have emerged as a prominent area of research. These microsensors not only fulfill the technical requirements for monitoring animal physiological information but also offer an ideal platform for integration. They have been extensively studied for their ability to monitor animal physiological information in a minimally invasive manner, characterized by their bloodless, painless features, and exceptional performance. The development of implantable electrochemical microsensors for in vivo monitoring of animal physiological information has witnessed significant scientific and technological advancements through dedicated efforts. This review commenced with a comprehensive discussion of the construction of microsensors, including the materials utilized and the methods employed for fabrication. Following this, we proceeded to explore the various implantation technologies employed for electrochemical microsensors. In addition, a comprehensive overview was provided of the various applications of implantable electrochemical microsensors, specifically in the monitoring of diseases and the investigation of disease mechanisms. Lastly, a concise conclusion was conducted on the recent advancements and significant obstacles pertaining to the practical implementation of implantable electrochemical microsensors.
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Affiliation(s)
- Jin Zhou
- Laboratory of Agricultural Information Intelligent Sensing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, People's Republic of China
| | - Shenghan Zhou
- Laboratory of Agricultural Information Intelligent Sensing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, People's Republic of China
| | - Peidi Fan
- Laboratory of Agricultural Information Intelligent Sensing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, People's Republic of China
| | - Xunjia Li
- Laboratory of Agricultural Information Intelligent Sensing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, People's Republic of China
- ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311200, People's Republic of China
| | - Yibin Ying
- Laboratory of Agricultural Information Intelligent Sensing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, People's Republic of China
- ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311200, People's Republic of China
| | - Jianfeng Ping
- Laboratory of Agricultural Information Intelligent Sensing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, People's Republic of China.
- ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311200, People's Republic of China.
| | - Yuxiang Pan
- Laboratory of Agricultural Information Intelligent Sensing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, People's Republic of China.
- ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311200, People's Republic of China.
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Li Y, Liu Y, Liu S, Gao M, Wang W, Chen K, Huang L, Liu Y. Diabetic vascular diseases: molecular mechanisms and therapeutic strategies. Signal Transduct Target Ther 2023; 8:152. [PMID: 37037849 PMCID: PMC10086073 DOI: 10.1038/s41392-023-01400-z] [Citation(s) in RCA: 216] [Impact Index Per Article: 108.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 02/19/2023] [Accepted: 02/28/2023] [Indexed: 04/12/2023] Open
Abstract
Vascular complications of diabetes pose a severe threat to human health. Prevention and treatment protocols based on a single vascular complication are no longer suitable for the long-term management of patients with diabetes. Diabetic panvascular disease (DPD) is a clinical syndrome in which vessels of various sizes, including macrovessels and microvessels in the cardiac, cerebral, renal, ophthalmic, and peripheral systems of patients with diabetes, develop atherosclerosis as a common pathology. Pathological manifestations of DPDs usually manifest macrovascular atherosclerosis, as well as microvascular endothelial function impairment, basement membrane thickening, and microthrombosis. Cardiac, cerebral, and peripheral microangiopathy coexist with microangiopathy, while renal and retinal are predominantly microangiopathic. The following associations exist between DPDs: numerous similar molecular mechanisms, and risk-predictive relationships between diseases. Aggressive glycemic control combined with early comprehensive vascular intervention is the key to prevention and treatment. In addition to the widely recommended metformin, glucagon-like peptide-1 agonist, and sodium-glucose cotransporter-2 inhibitors, for the latest molecular mechanisms, aldose reductase inhibitors, peroxisome proliferator-activated receptor-γ agonizts, glucokinases agonizts, mitochondrial energy modulators, etc. are under active development. DPDs are proposed for patients to obtain more systematic clinical care requires a comprehensive diabetes care center focusing on panvascular diseases. This would leverage the advantages of a cross-disciplinary approach to achieve better integration of the pathogenesis and therapeutic evidence. Such a strategy would confer more clinical benefits to patients and promote the comprehensive development of DPD as a discipline.
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Affiliation(s)
- Yiwen Li
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, 100091, China
| | - Yanfei Liu
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, 100091, China
- The Second Department of Gerontology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China
| | - Shiwei Liu
- Department of Nephrology and Endocrinology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, 100102, China
| | - Mengqi Gao
- Department of Nephrology and Endocrinology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, 100102, China
| | - Wenting Wang
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, 100091, China
| | - Keji Chen
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, 100091, China.
| | - Luqi Huang
- China Center for Evidence-based Medicine of TCM, China Academy of Chinese Medical Sciences, Beijing, 100010, China.
| | - Yue Liu
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, 100091, China.
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6
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Ghannam N, Alahmed S, Aldahash R, Aljohani N, Alshammary A, Amir A, Kamal A, Khader S, Salah M, Shalabi H, Abdallah A, Elboghdady A. Addressing the Continuum of Dysglycaemia and Vascular Complications in Prediabetes and Type 2 Diabetes: Need for Early and Intensive Treatment. Diabetes Metab Syndr Obes 2023; 16:105-115. [PMID: 36760588 PMCID: PMC9844108 DOI: 10.2147/dmso.s396621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 12/23/2022] [Indexed: 01/18/2023] Open
Abstract
The onset of type 2 diabetes increases the risk of vascular complications and death. We know now that that this risk begins long before the diabetes diagnosis. Prediabetes and type 2 diabetes are not separate entities in practice and exist within a continuum of dysglycaemia and vascular risk that increases in severity over time. This excess risk requires early intervention with lifestyle therapy supported with pharmacologic antidiabetic therapy, intensified promptly where necessary throughout the duration of the diabetes continuum. Metformin is an evidence-based treatment for preventing prediabetes and improves cardiovascular outcomes in people with type 2 diabetes from diagnosis onwards. Newer agents (SGLT2 inhibitors and GLP-1 agonists) are appropriate for people presenting with type 2 diabetes and significant cardiovascular comorbidity. Additional therapies should be used without delay to achieve patients' individualised HbA1c goals and to minimise cardiovascular risk.
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Affiliation(s)
- Nadia Ghannam
- Ghannam Clinic, Jeddah, Saudi Arabia
- Correspondence: Nadia Ghannam, Ghannam Clinic, King Abdulaziz Road, Jeddah, 21411, Saudi Arabia, Email
| | | | - Raed Aldahash
- Ministry of National Guard (Health Affairs) and King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | | | - Afaf Alshammary
- Ministry of National Guard (Health Affairs), King Abdulaziz Medical City, Riyadh and King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Ashraf Amir
- Family Medicine International Medical Center, Jeddah, Saudi Arabia
| | | | - Said Khader
- Dr. Sulaiman Al Habib Medical Group, Riyadh, Saudi Arabia
| | - Mohammed Salah
- Cairo University, Cairo, Egypt and GNP Hospital, Jeddah, Saudi Arabia
| | - Hani Shalabi
- University of Jeddah, Jeddah, Saudi Arabia
- Dr. Soliman Fakeeh Hospital, Jeddah, Saudi Arabia
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Gottwald-Hostalek U, Gwilt M. Vascular complications in prediabetes and type 2 diabetes: a continuous process arising from a common pathology. Curr Med Res Opin 2022; 38:1841-1851. [PMID: 35833523 DOI: 10.1080/03007995.2022.2101805] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
The term, "prediabetes", describes a state of hyperglycaemia that is intermediate between true normoglycaemia and the diagnostic cut-offs for indices of glycaemia that are used to diagnose type 2 diabetes. The presence of prediabetes markedly increases the risk of developing type 2 diabetes. Numerous randomized, controlled evaluations of various agents have demonstrated significant prevention or delay of the onset of type 2 diabetes in subjects with prediabetes. Intensive lifestyle interventions and metformin have been studied most widely, with the lifestyle intervention being more effective in the majority of subjects. The application of therapeutic interventions at the time of prediabetes to preserve long-term outcomes has been controversial, however, due to a lack of evidence relating to the pathogenic effects of prediabetes and the effectiveness of interventions to produce a long-term clinical benefit. Recent studies have confirmed that prediabetes, however defined, is associated with a significantly increased risk of macrovascular and microvascular complications essentially identical to those of diabetes, and also with subclinical derangements of the function of microvasculature and neurons that likely signify increased risk of compilations in future. Normoglycaemia, prediabetes and type 2 diabetes appear to be part of a continuum of increased risk of adverse outcomes. Long-term (25-30 years) post-trial follow up of two major diabetes prevention trials have shown that short-term interventions to prevent diabetes lead to long-term reductions in the risk of complications. These findings support the concept of therapeutic intervention to preserve long-term health in people with prediabetes before type 2 diabetes becomes established.
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Abstract
It is increasingly recognized that diabetic neuropathy is associated with early diabetes, prediabetes, and the metabolic syndrome. Early detection and diagnosis are important to slow progression and prevent complications. Although strict glucose control is an effective treatment in type 1 diabetes, it is less effective in type 2 diabetes. There is a growing body of literature that lifestyle interventions may be able to prevent or slow progression of neuropathy in type 2 diabetes. In addition to the typical distal symmetric polyneuropathy, there are many types of "atypical" diabetic neuropathies that are important to recognize.
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Affiliation(s)
- Lindsay A Zilliox
- Department of Neurology, University of Maryland School of Medicine & Maryland VA Healthcare System, 3S-130, 110 South Paca Street, Baltimore, MD 21201-1595, USA.
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Xu X, Xu DS. Prospects for the application of transcranial magnetic stimulation in diabetic neuropathy. Neural Regen Res 2021; 16:955-962. [PMID: 33229735 PMCID: PMC8178790 DOI: 10.4103/1673-5374.297062] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Encouraging results have been reported for the use of transcranial magnetic stimulation-based nerve stimulation in studies of the mechanisms of neurological regulation, nerve injury repair, and nerve localization. However, to date, there are only a few reviews on the use of transcranial magnetic stimulation for diabetic neuropathy. Patients with diabetic neuropathy vary in disease progression and show neuropathy in the early stage of the disease with mild symptoms, making it difficult to screen and identify. In the later stage of the disease, irreversible neurological damage occurs, resulting in treatment difficulties. In this review, we summarize the current state of diabetic neuropathy research and the prospects for the application of transcranial magnetic stimulation in diabetic neuropathy. We review significant studies on the beneficial effects of transcranial magnetic stimulation in diabetic neuropathy treatment, based on the outcomes of its use to treat neurodegeneration, pain, blood flow change, autonomic nervous disorders, vascular endothelial injury, and depression. Collectively, the studies suggest that transcranial magnetic stimulation can produce excitatory/inhibitory stimulation of the cerebral cortex or local areas, promote the remodeling of the nervous system, and that it has good application prospects for the localization of the injury, neuroprotection, and the promotion of nerve regeneration. Therefore, transcranial magnetic stimulation is useful for the screening and early treatment of diabetic neuropathy. Transcranial magnetic stimulation can also alleviate pain symptoms by changing the cortical threshold and inhibiting the conduction of sensory information in the thalamo-spinal pathway, and therefore it has therapeutic potential for the treatment of pain and pain-related depressive symptoms in patients with diabetic neuropathy. Additionally, based on the effect of transcranial magnetic stimulation on local blood flow and its ability to change heart rate and urine protein content, transcranial magnetic stimulation has potential in the treatment of autonomic nerve dysfunction and vascular injury in diabetic neuropathy. Furthermore, oxidative stress and the inflammatory response are involved in the process of diabetic neuropathy, and transcranial magnetic stimulation can reduce oxidative damage. The pathological mechanisms of diabetic neuropathy should be further studied in combination with transcranial magnetic stimulation technology.
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Affiliation(s)
- Xi Xu
- Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
| | - Dong-Sheng Xu
- Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine; School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Meyhöfer S, Schmid SM. [Diabetes complications - diabetes and the nervous system]. Dtsch Med Wochenschr 2020; 145:1599-1605. [PMID: 33142326 DOI: 10.1055/a-1038-0102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Diabetes mellitus is a chronic metabolic disease associated with multiple long-term complications. Besides macro- and microvascular complications, patient's well-being can be severely impaired by complications affecting the nervous system. About 50 % of patients with diabetes suffer from polyneuropathy. Moreover, the risk of developing cognitive impairment and dementia is also increased in older people with diabetes. Insufficient glycemic control, young age at diagnosis of diabetes are discussed as risk factors for developing diabetes complications. The early identification and prevention of factors predicting diabetes complications that affect the nervous system are still challenging and in need for further research.
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Tesfaye S, Sloan G. Diabetic Polyneuropathy - Advances in Diagnosis and Intervention Strategies. EUROPEAN ENDOCRINOLOGY 2020; 16:15-20. [PMID: 32595764 DOI: 10.17925/ee.2020.16.1.15] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 01/28/2020] [Indexed: 12/19/2022]
Abstract
Over half of people with diabetes mellitus develop diabetic polyneuropathy (DPN), which is a major cause of reduced quality of life due to disabling neuropathic pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation. The latter represents a major health and economic burden, with lower limb amputation rates related to diabetes increasing in the UK. There is a need for early diagnosis of DPN so that early management strategies may be instigated, such as achieving tight glucose control and management of cardiovascular risk factors, in an attempt to slow its progression. To this end, a one-stop microvascular assessment involving a combined eye, foot and renal screening clinic has proven feasible in the UK. Unfortunately, there are currently no approved disease-modifying therapies for DPN. Some disease-modifying agents have demonstrated efficacy, but further large trials using appropriate clinical endpoints are required before these treatments can be routinely recommended. There has been emerging evidence highlighting a reduction in vitamin D levels in cases of painful DPN and the potential for vitamin D supplementation in deficient individuals to improve neuropathic pain; however, this needs to be proved in randomised clinical trials. The use of established agents for neuropathic pain in DPN is limited by poor efficacy and adverse effects, but patient stratification using methods such as pain phenotyping are being tested to determine whether this improves the outcomes of such agents in clinical studies. In addition, innovative approaches such as the topical 8% capsaicin patch, new methods of electrical stimulation and novel therapeutic targets such as NaV1.7 offer promise for the future. This article aims to discuss the challenges of diagnosing and managing DPN and to review current and emerging lifestyle interventions and therapeutic options.
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Affiliation(s)
- Solomon Tesfaye
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Gordon Sloan
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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12
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Javed S, Hayat T, Menon L, Alam U, Malik RA. Diabetic peripheral neuropathy in people with type 2 diabetes: too little too late. Diabet Med 2020; 37:573-579. [PMID: 31797434 DOI: 10.1111/dme.14194] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/30/2019] [Indexed: 12/12/2022]
Abstract
Diabetic peripheral neuropathy in people with type 2 diabetes is poorly managed because of its insidious onset, delayed diagnosis and more complex aetiology resulting from the contribution of not only hyperglycaemia, but also ageing, hyperlipidaemia, hypertension and obesity. Because there is no US Food and Drug Adminstration-approved disease-modifying therapy for diabetic peripheral neuropathy, the key to ameliorating it in type 2 diabetes has to be through earlier diagnosis and timely multi-factorial risk factor reduction. The management of painful diabetic peripheral neuropathy also requires a detailed appraisal of the choice of therapy, taking into account efficacy, patient wishes, comorbidities, side effect profile and potential for abuse.
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Affiliation(s)
- S Javed
- Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester, UK
| | - T Hayat
- Primary Health Care Corporation, Doha, Qatar
| | - L Menon
- Department of Medicine, Weill-Cornell Medicine-Qatar, Doha, Qatar
| | - U Alam
- Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK
| | - R A Malik
- Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester, UK
- Department of Medicine, Weill-Cornell Medicine-Qatar, Doha, Qatar
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Abstract
Sensory polyneuropathies, which are caused by dysfunction of peripheral sensory nerve fibers, are a heterogeneous group of disorders that range from the common diabetic neuropathy to the rare sensory neuronopathies. The presenting symptoms, acuity, time course, severity, and subsequent morbidity vary and depend on the type of fiber that is affected and the underlying cause. Damage to small thinly myelinated and unmyelinated nerve fibers results in neuropathic pain, whereas damage to large myelinated sensory afferents results in proprioceptive deficits and ataxia. The causes of these disorders are diverse and include metabolic, toxic, infectious, inflammatory, autoimmune, and genetic conditions. Idiopathic sensory polyneuropathies are common although they should be considered a diagnosis of exclusion. The diagnostic evaluation involves electrophysiologic testing including nerve conduction studies, histopathologic analysis of nerve tissue, serum studies, and sometimes autonomic testing and cerebrospinal fluid analysis. The treatment of these diseases depends on the underlying cause and may include immunotherapy, mitigation of risk factors, symptomatic treatment, and gene therapy, such as the recently developed RNA interference and antisense oligonucleotide therapies for transthyretin familial amyloid polyneuropathy. Many of these disorders have no directed treatment, in which case management remains symptomatic and supportive. More research is needed into the underlying pathophysiology of nerve damage in these polyneuropathies to guide advances in treatment.
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Affiliation(s)
- Kelly Graham Gwathmey
- Virginia Commonwealth University, Department of Neurology, 1101 E. Marshall Street, PO Box 980599, Richmond, VA 23298, USA
| | - Kathleen T Pearson
- Virginia Commonwealth University, Department of Neurology, 1101 E. Marshall Street, PO Box 980599, Richmond, VA 23298, USA
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14
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Herder C, Roden M, Ziegler D. Novel Insights into Sensorimotor and Cardiovascular Autonomic Neuropathy from Recent-Onset Diabetes and Population-Based Cohorts. Trends Endocrinol Metab 2019; 30:286-298. [PMID: 30935671 DOI: 10.1016/j.tem.2019.02.007] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 02/22/2019] [Accepted: 02/28/2019] [Indexed: 12/19/2022]
Abstract
The most prevalent chronic complications of diabetes are diabetic neuropathies, among which distal sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) are the best studied. Their major clinical sequelae such as foot ulcers, neuropathic pain, and orthostatic hypotension are associated with lower quality of life and increased risk of mortality. Here we discuss the recent insights into DSPN and CAN focusing on two prospective cohorts; that is, the German Diabetes Study (GDS) including recent-onset diabetes patients and the population-based Cooperative Health Research in the Region of Augsburg, Germany (KORA) surveys. The insights from these studies investigating novel tools for early detection and prediction of (pre)diabetic neuropathy as well as biomarkers of oxidative stress and inflammation should ultimately culminate in improving the health care of patients affected by this serious condition.
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Affiliation(s)
- Christian Herder
- Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; These authors contributed equally.
| | - Michael Roden
- Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Dan Ziegler
- Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; These authors contributed equally.
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15
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Chakarova N, Dimova R, Grozeva G, Tankova T. Assessment of glucose variability in subjects with prediabetes. Diabetes Res Clin Pract 2019; 151:56-64. [PMID: 30935927 DOI: 10.1016/j.diabres.2019.03.038] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 03/02/2019] [Accepted: 03/27/2019] [Indexed: 11/15/2022]
Abstract
UNLABELLED The aim of the study was to assess glucose variability in subjects with prediabetes by means of CGM. MATERIAL AND METHODS 32 subjects with prediabetes - mean age 56.6 ± 9.6 years, mean BMI 30.3 ± 5.3 kg/m2 and 18 subjects with normal glucose tolerance (NGT) - mean age 54.4 ± 9.9 years, mean BMI 24.8 ± 6.9 kg/m2, were enrolled. Glucose tolerance was studied during OGTT. HbA1c was measured by NGSP certified method. CGM was performed with FreeStyle Libre Pro sensor. RESULTS The following indices of glucose variability were significantly higher in the prediabetes group - CV (p < 0.041), J-index (p < 0.014), CONGA (p < 0.047) and GRADE (p < 0.036). A significant increase in HbA1c (p < 0.036), mean interstitial glucose (p < 0.025), time above range (p < 0.018) and a significant decrease in time in range (p < 0.014) was found in prediabetes compared to NGT. Significant correlations between HbA1c and LBGI (r = -0.33, p = 0.02), HBGI (r = 0.31, p = 0.03), CONGA (r = 0.36, p = 0.01), J-index (r = 0.37, p = 0.01) and M-value (r = -0.34, p = 0.02) were established. CONCLUSION Glucose variability is significantly increased in prediabetes and is an additional parameter in the assessment of glucose homeostasis even at these early stages of glucose dysregulation.
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Affiliation(s)
- Nevena Chakarova
- Department of Diabetology, Clinical Center of Endocrinology and Gerontology, Medical University Sofia, Bulgaria.
| | - Rumyana Dimova
- Department of Diabetology, Clinical Center of Endocrinology and Gerontology, Medical University Sofia, Bulgaria
| | - Greta Grozeva
- Department of Diabetology, Clinical Center of Endocrinology and Gerontology, Medical University Sofia, Bulgaria
| | - Tsvetalina Tankova
- Department of Diabetology, Clinical Center of Endocrinology and Gerontology, Medical University Sofia, Bulgaria
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16
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Bönhof GJ, Herder C, Strom A, Papanas N, Roden M, Ziegler D. Emerging Biomarkers, Tools, and Treatments for Diabetic Polyneuropathy. Endocr Rev 2019; 40:153-192. [PMID: 30256929 DOI: 10.1210/er.2018-00107] [Citation(s) in RCA: 138] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 08/23/2018] [Indexed: 12/12/2022]
Abstract
Diabetic neuropathy, with its major clinical sequels, notably neuropathic pain, foot ulcers, and autonomic dysfunction, is associated with substantial morbidity, increased risk of mortality, and reduced quality of life. Despite its major clinical impact, diabetic neuropathy remains underdiagnosed and undertreated. Moreover, the evidence supporting a benefit for causal treatment is weak at least in patients with type 2 diabetes, and current pharmacotherapy is largely limited to symptomatic treatment options. Thus, a better understanding of the underlying pathophysiology is mandatory for translation into new diagnostic and treatment approaches. Improved knowledge about pathogenic pathways implicated in the development of diabetic neuropathy could lead to novel diagnostic techniques that have the potential of improving the early detection of neuropathy in diabetes and prediabetes to eventually embark on new treatment strategies. In this review, we first provide an overview on the current clinical aspects and illustrate the pathogenetic concepts of (pre)diabetic neuropathy. We then describe the biomarkers emerging from these concepts and novel diagnostic tools and appraise their utility in the early detection and prediction of predominantly distal sensorimotor polyneuropathy. Finally, we discuss the evidence for and limitations of the current and novel therapy options with particular emphasis on lifestyle modification and pathogenesis-derived treatment approaches. Altogether, recent years have brought forth a multitude of emerging biomarkers reflecting different pathogenic pathways such as oxidative stress and inflammation and diagnostic tools for an early detection and prediction of (pre)diabetic neuropathy. Ultimately, these insights should culminate in improving our therapeutic armamentarium against this common and debilitating or even life-threatening condition.
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Affiliation(s)
- Gidon J Bönhof
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.,German Center for Diabetes Research, Munich-Neuherberg, Neuherberg, Partner Düsseldorf, Düsseldorf, Germany.,Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Alexander Strom
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.,German Center for Diabetes Research, Munich-Neuherberg, Neuherberg, Partner Düsseldorf, Düsseldorf, Germany
| | - Nikolaos Papanas
- Second Department of Internal Medicine, Diabetes Center, Diabetic Foot Clinic, Democritus University of Thrace, Alexandroupolis, Greece
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.,German Center for Diabetes Research, Munich-Neuherberg, Neuherberg, Partner Düsseldorf, Düsseldorf, Germany.,Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.,German Center for Diabetes Research, Munich-Neuherberg, Neuherberg, Partner Düsseldorf, Düsseldorf, Germany.,Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
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17
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Wang H, Zhang H, Cao F, Lu J, Tang J, Li H, Zhang Y, Feng B, Tang Z. Protection of insulin‑like growth factor 1 on experimental peripheral neuropathy in diabetic mice. Mol Med Rep 2018; 18:4577-4586. [PMID: 30221656 DOI: 10.3892/mmr.2018.9435] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Accepted: 07/19/2018] [Indexed: 11/05/2022] Open
Abstract
The present study investigated whether insulin‑like growth factor‑1 (IGF‑1) exerts a protective effect against neuropathy in diabetic mice and its potential underlying mechanisms. Mice were divided into four groups: Db/m (control), db/db (diabetes), IGF‑1‑treated db/db and IGF‑1‑picropodophyllin (PPP)‑treated db/db. Behavioral studies were conducted using the hot plate and von Frey methods at 6 weeks of age prior to treatment. The motor nerve conduction velocity (NCV) of the sciatic nerve was measured using a neurophysiological method at 8 weeks of age. The alterations in the expression levels of IGF‑1 receptor (IGF‑1R), c‑Jun N‑terminal kinase (JNK), extracellular signal‑regulated kinase (ERK), p38 and effect of IGF‑1 on the sciatic nerve morphology were observed by western blotting and electron microscopy. Compared with the control group, the diabetes group developed hypoalgesia after 12 weeks, and neurological lesions improved following an intraperitoneal injection of recombinant (r)IGF‑1. The sciatic NCV in the diabetes group was significantly lower compared with the control group. The sciatic NCV improved following rIGF‑1 intervention; however, was impaired following administration of the IGF‑1 receptor antagonist, PPP. The myelin sheath in the sciatic nerve of the diabetes group was significantly more impaired compared with the control group. The myelin sheath in the sciatic nerves of the rIGF‑1‑treated group was significantly improved compared with the diabetes group; whereas, they were significantly impaired following administration of the IGF‑1R inhibitor. In addition, the expression of IGF‑1R, phosphorylated (p)‑JNK and p‑ERK of sciatic nerves in the db/db mice was significantly increased following treatment with IGF‑1. The expression levels of these proteins were significantly lower in the IGF‑1‑PPP group compared with the IGF‑1 group; however, no significant difference was observed in the expression levels of p‑p38 following treatment with IGF‑1. The results of the present study demonstrated that IGF‑1 may improve neuropathy in diabetic mice. This IGF‑1‑induced neurotrophic effect may be associated with the increased phosphorylation levels of JNK and ERK, not p38; however, it was attenuated by administration of an IGF‑1R antagonist.
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Affiliation(s)
- Hua Wang
- Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China
| | - Hao Zhang
- Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China
| | - Fuming Cao
- Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China
| | - Jiaping Lu
- Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China
| | - Jin Tang
- Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China
| | - Huizhi Li
- Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China
| | - Yiyun Zhang
- Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China
| | - Bo Feng
- Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China
| | - Zhaosheng Tang
- Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China
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18
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Meisinger C, Bongaerts BWC, Heier M, Amann U, Kowall B, Herder C, Rückert-Eheberg IM, Rathmann W, Ziegler D. Neuropathic pain is not adequately treated in the older general population: Results from the KORA F4 survey. Pharmacoepidemiol Drug Saf 2018; 27:806-814. [PMID: 29797371 DOI: 10.1002/pds.4559] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 04/03/2018] [Accepted: 04/22/2018] [Indexed: 12/17/2022]
Abstract
PURPOSE We evaluated the pharmacological treatment of distal sensorimotor polyneuropathy (DSPN) among older subjects from the general population. METHODS The study included subjects aged 61 to 82 years from the KORA F4 survey (2006-2008). DSPN was defined as the presence of bilaterally impaired foot-vibration perception and/or bilaterally impaired foot-pressure sensation. Pain intensity was assessed with the painDETECT questionnaire. RESULTS From the included 1076 older persons, 172 (16%) persons reported pain in the lower extremities and DSPN was present in 150 (14%) subjects. Forty-eight people with pain in the lower extremities reported DSPN. Only 38% of the subjects with DSPN reporting an average pain level of ≥4 during the past 4 weeks received medical treatment, predominantly nonsteroidal anti-inflammatory drugs (NSAIDs 20% and opioids 12%). The medication of choice for neuropathic pain, antidepressants, anticonvulsants, and opioids was relatively being underused. However, opioids and neuropathy preparations were prescribed preferably for subjects with painful DSPN. CONCLUSIONS In the older general population, only a small proportion of subjects with painful DSPN receive analgesic pharmacotherapy. Although not recommended by guidelines for the treatment of neuropathic pain, NSAIDs were the most frequently used class of analgesic drugs.
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Affiliation(s)
- Christa Meisinger
- Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, München-Neuherberg, Germany.,Chair of Epidemiology at UNIKA-T, Ludwig-Maximilians-Universität München, Augsburg, Germany
| | - Brenda W C Bongaerts
- Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
| | - Margit Heier
- Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, München-Neuherberg, Germany
| | - Ute Amann
- Chair of Epidemiology at UNIKA-T, Ludwig-Maximilians-Universität München, Augsburg, Germany
| | - Bernd Kowall
- Center of Clinical Epidemiology, Institute for Medical Informatics, Biometry and Epidemiology, Medical Faculty, University Duisburg-Essen, Essen, Germany
| | - Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.,German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Ina-Maria Rückert-Eheberg
- Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, München-Neuherberg, Germany
| | - Wolfgang Rathmann
- Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
| | - Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.,German Center for Diabetes Research (DZD), München-Neuherberg, Germany.,Department of Endocrinology and Diabetology, University Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
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19
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Affiliation(s)
- Kalliopi Pafili
- 1 Second Department of Internal Medicine, Diabetes Centre, Diabetic Foot Clinic, Democritus University of Thrace, Alexandroupolis, Greece
| | - Nikolaos Papanas
- 1 Second Department of Internal Medicine, Diabetes Centre, Diabetic Foot Clinic, Democritus University of Thrace, Alexandroupolis, Greece
| | - Dan Ziegler
- 2 Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany.,3 Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
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20
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Xu T, Weng Z, Pei C, Yu S, Chen Y, Guo W, Wang X, Luo P, Sun J. The relationship between neutrophil-to-lymphocyte ratio and diabetic peripheral neuropathy in Type 2 diabetes mellitus. Medicine (Baltimore) 2017; 96:e8289. [PMID: 29137012 PMCID: PMC5690705 DOI: 10.1097/md.0000000000008289] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
To explore the relationship between neutrophil-to-lymphocyte ratio (NLR) and diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus.A total of 557 newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients were recruited, including 397 T2DM patients without complication (DM group) as well as 160 T2DM patients complicated with DPN (DPN group). Student t test, Mann-Whitney U test, or χ test was applied to the data of the 2 groups, including the levels of neutrophils and lymphocytes as well as the NLR values of peripheral blood and other biochemistry indexes; Pearson correlation analysis was used to calculate the correlation of NLR and detected factors; risk factors of DPN were estimated via logistic regression analysis and multivariate analysis.The values of triglyceride (TG), neutrophils, fasting insulin, urinary albumin, and 2 hour postglucose in DPN group were significantly higher than those of the DM group, whereas the number of lymphocytes of DPN group was considerably lower than that of the DM group (P < .05 respectively); NLR values were remarkably higher in DPN group compared with those of DM group (2.58 ± 0.50 vs 2.18 ± 0.61, P < .001); logistic regression analysis showed that NLR (P = .002, OR = 4.960, 95% CI = 1.843-13.349) was a risk factor of DPN. Multivariate logistic regression analysis showed that DPN was independently related to NLR (P = .002, OR = 4.960, 95% CI = 1.843-13.349). The ROC curve analysis confirmed that the optimal cut-off point, specificity, and sensitivity in diagnosing DPN by NLR were 2.13%, 48.1%, and 81.3% respectively.Our results showed that NLR is significantly correlated with DPN, which suggested that NLR may be an independent risk factor of DPN.
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Affiliation(s)
- Tingting Xu
- Zhujiang Hospital, Southern Medical University
| | - Zihua Weng
- Zhujiang Hospital, Southern Medical University
| | - Chu Pei
- State Key Laboratory of Respiratory Disease, National Clinical Center for Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Siyuan Yu
- Zhujiang Hospital, Southern Medical University
| | - Yating Chen
- Zhujiang Hospital, Southern Medical University
| | - Wenjie Guo
- Zhujiang Hospital, Southern Medical University
| | | | - Peng Luo
- Zhujiang Hospital, Southern Medical University
| | - Jia Sun
- Zhujiang Hospital, Southern Medical University
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21
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Németh N, Putz Z, Istenes I, Körei AE, Vági OE, Kempler M, Gandhi R, Jermendy G, Tesfaye S, Tabák ÁG, Kempler P. Is there a connection between postprandial hyperglycemia and IGT related sensory nerve dysfunction? Nutr Metab Cardiovasc Dis 2017; 27:609-614. [PMID: 28676377 DOI: 10.1016/j.numecd.2017.05.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2016] [Revised: 05/03/2017] [Accepted: 05/04/2017] [Indexed: 01/24/2023]
Abstract
BACKGROUND AND AIMS To assess the risk factors for sensory nerve dysfunction in subjects with isolated impaired glucose tolerance (IGT). METHODS AND RESULTS Seventy-two people with isolated IGT (WHO 1999 criteria) and 39 gender and age-matched healthy volunteers underwent detailed clinical and neurological assessment including quantitative sensory testing using the Neurometer device (current perception threshold measurement on four limbs at three different frequencies). Sensory nerve dysfunction was defined as at least two abnormalities on any frequencies on the upper or lower limbs. Sensory nerve dysfunction was more prevalent among subjects with IGT compared to controls (58.3 vs. 10.3%, OR: 11.23, 95%CI: 3.57-35.35). This association was not influenced by BMI, systolic and diastolic blood pressure, heart rate and autonomic neuropathy (multiple adjusted OR: 13.87, 95%CI: 3.18-60.58), but further adjustment for glycaemic measures abolished the association (OR: 1.58, 95%CI: 0.07-35.68). Assessing the components of glycaemic measures separately, the association between sensory nerve dysfunction and IGT was not affected by HbA1c (OR: 13.94, 95%CI: 1.84-105.5). It was, however, substantially attenuated by fasting plasma glucose (OR: 6.75, 95%CI: 1.33-34.27) while the significance was lost after adjustment for 120 min postload glucose level (OR: 3.76, 95%CI: 0.26-54.10). In the pooled population assessed, independent determinants of sensory nerve dysfunction were older age, 120 min glucose, higher height and cardiovascular autonomic neuropathy at near significance. CONCLUSIONS Sensory nerve dysfunction amongst subjects with IGT was not explained by cardiovascular covariates, only by glycaemic measures. In addition to 120 min glucose, cardiovascular autonomic neuropathy at borderline significance, age, and height were the independent determinants of sensory nerve dysfunction.
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Affiliation(s)
- N Németh
- 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
| | - Z Putz
- 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary
| | - I Istenes
- 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary
| | - A E Körei
- 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary
| | - O E Vági
- 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary
| | - M Kempler
- 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary; 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
| | - R Gandhi
- Royal Hallamshire Hospital, Sheffield, UK
| | - G Jermendy
- 3rd Department of Internal Medicine, Bajcsy-Zsilinszky Hospital, Budapest, Hungary
| | - S Tesfaye
- Royal Hallamshire Hospital, Sheffield, UK
| | - Á G Tabák
- 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary; Department of Epidemiology and Public Health, University College London, London, UK
| | - P Kempler
- 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary
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22
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Herder C, Kannenberg JM, Huth C, Carstensen-Kirberg M, Rathmann W, Koenig W, Heier M, Püttgen S, Thorand B, Peters A, Roden M, Meisinger C, Ziegler D. Proinflammatory Cytokines Predict the Incidence and Progression of Distal Sensorimotor Polyneuropathy: KORA F4/FF4 Study. Diabetes Care 2017; 40:569-576. [PMID: 28174259 DOI: 10.2337/dc16-2259] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Accepted: 01/05/2017] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Experimental and epidemiological studies have implicated inflammatory processes in the pathogenesis of distal sensorimotor polyneuropathy (DSPN), but prospective studies are lacking. We hypothesized that biomarkers of inflammation predict the development and progression of DSPN in a population-based cohort. RESEARCH DESIGN AND METHODS This study was based on participants aged 62-81 years from the Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort, with a mean follow-up of 6.5 years. The predictive value of systemic levels of eight biomarkers of inflammation was assessed for incident DSPN in 133 incident case subjects and 397 individuals without incident DSPN, and for DSPN progression in 57 patients with prevalent DSPN at both time points. RESULTS Higher hs-CRP, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1 receptor antagonist (IL-1RA), and soluble intercellular adhesion molecule (sICAM-1) and lower adiponectin levels were associated with incident DSPN in age- and sex-adjusted analysis; IL-18 and omentin were not. IL-6 (odds ratio 1.31 [95% CI 1.00-1.71]) and TNF-α (odds ratio 1.31 [95% CI 1.03-1.67]) remained associated with incident DSPN after adjusting for known DSPN risk factors. The addition of both cytokines to a clinical risk model improved model fit and reclassification. sICAM-1 and IL-1RA were positively associated with progression of DSPN. CONCLUSIONS Systemic subclinical and vascular inflammation predicted both the onset and progression of DSPN over 6.5 years in an older general population. Thus modulation of inflammatory processes may be relevant to prevent and/or treat diabetic neuropathy.
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Affiliation(s)
- Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany .,German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Julia M Kannenberg
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.,German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Cornelia Huth
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany.,Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Maren Carstensen-Kirberg
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.,German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Wolfgang Rathmann
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany.,Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Wolfgang Koenig
- Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.,German Center for Cardiovascular Research (DZHK), Partner site Munich Heart Alliance, Munich, Germany
| | - Margit Heier
- Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Sonja Püttgen
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.,German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Barbara Thorand
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany.,Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Annette Peters
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany.,Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.,German Center for Diabetes Research (DZD), München-Neuherberg, Germany.,Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Christa Meisinger
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany.,Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.,German Center for Diabetes Research (DZD), München-Neuherberg, Germany.,Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
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O'Brien MJ, Moran MR, Tang JW, Vargas MC, Talen M, Zimmermann LJ, Ackermann RT, Kandula NR. Patient Perceptions About Prediabetes and Preferences for Diabetes Prevention. DIABETES EDUCATOR 2016; 42:667-677. [PMID: 27621093 DOI: 10.1177/0145721716666678] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
PURPOSE The purpose of this study was to explore how adults with prediabetes perceive their risk of developing diabetes and examine their preferences for evidence-based treatment options to prevent diabetes. METHODS A qualitative study was conducted in 2 large Midwest primary care practices, involving in-depth semistructured interviews with 35 adult patients with prediabetes. RESULTS This ethnically diverse (77% nonwhite) sample of middle-aged primary care patients exhibited multiple diabetes risk factors. Knowledge gaps about prediabetes and its medical management were pervasive. Most patients overestimated the risk of developing diabetes and were not familiar with evidence-based treatment options for prediabetes. They suggested that receiving brief, yet specific information about these topics during the study interview motivated them to act. The majority of participants considered both intensive lifestyle intervention and metformin acceptable treatment options. Many preferred initial treatment with intensive lifestyle intervention but would take metformin if their efforts at lifestyle change failed and their primary care physician recommended it. Some participants expressed wanting to combine both treatments. CONCLUSIONS This qualitative study highlights potential opportunities to promote patient-centered dialogue about prediabetes in primary care settings. Providing patients specific information about the risk of developing diabetes and evidence-based treatment options to prevent or delay its onset may encourage action. Physicians' prediabetes counseling efforts should be informed by the finding that most patients consider both intensive lifestyle intervention and metformin acceptable treatment options.
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Affiliation(s)
- Matthew J O'Brien
- Division of General Internal Medicine and Geriatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA (Dr O'Brien, Ms Vargas, Dr Zimmermann, Dr Ackermann, Dr Kandula),Center for Community Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA (Dr O'Brien, Ms Moran, Ms Vargas, Dr Ackermann, Dr Kandula)
| | - Margaret R Moran
- Center for Community Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA (Dr O'Brien, Ms Moran, Ms Vargas, Dr Ackermann, Dr Kandula)
| | - Joyce W Tang
- Section of Hospital Medicine, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois, USA (Dr Tang)
| | - Maria C Vargas
- Center for Community Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA (Dr O'Brien, Ms Moran, Ms Vargas, Dr Ackermann, Dr Kandula)
| | - Mary Talen
- Northwestern Family Medicine Residency Program, Erie Family Health Center, Chicago, Illinois, USA (Dr Talen)
| | - Laura J Zimmermann
- Division of General Internal Medicine and Geriatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA (Dr O'Brien, Ms Vargas, Dr Zimmermann, Dr Ackermann, Dr Kandula),Erie Family Health Center, Chicago, Illinois, USA (Dr Zimmermann)
| | - Ronald T Ackermann
- Division of General Internal Medicine and Geriatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA (Dr O'Brien, Ms Vargas, Dr Zimmermann, Dr Ackermann, Dr Kandula),Center for Community Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA (Dr O'Brien, Ms Moran, Ms Vargas, Dr Ackermann, Dr Kandula)
| | - Namratha R Kandula
- Division of General Internal Medicine and Geriatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA (Dr O'Brien, Ms Vargas, Dr Zimmermann, Dr Ackermann, Dr Kandula),Center for Community Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA (Dr O'Brien, Ms Moran, Ms Vargas, Dr Ackermann, Dr Kandula),Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA (Dr Kandula)
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Abdul-Ghani M, DeFronzo RA, Jayyousi A. Prediabetes and risk of diabetes and associated complications: impaired fasting glucose versus impaired glucose tolerance: does it matter? Curr Opin Clin Nutr Metab Care 2016; 19:394-399. [PMID: 27389083 DOI: 10.1097/mco.0000000000000307] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
PURPOSE OF REVIEW The purpose of this review is to summarize the distinct metabolic and pathophysiologic phenotype of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and the subsequent clinical implications with regard to future type 2 diabetes mellitus (T2DM) and cardiovascular risk. RECENT FINDINGS Both IFG and IGT manifest the two core defects of T2DM, that is, insulin resistance and β-cell dysfunction. However, the site of insulin resistance and shape of β-cell dysfunction differ. These distinct metabolic and pathophysiologic phenotypes explain the greater cardiovascular disease (CVD) risk associated with an increase in the 2-h plasma glucose concentration, that is, IGT compared with an increase in the fasting plasma glucose (FPG) concentration, that is, IFG. Moreover, the increase in future T2DM risk in IFG study participants is, at least in part, explained by the strong correlation between the increase in FPG and the increase in 2-h plasma glucose concentration. SUMMARY Last, recent studies have reported the presence of diabetic microvascular complications, that is, retinopathy and neuropathy, at the IGT stage.Thus, a glucose load (e.g. oral glucose tolerance test) is required in study participants with elevated FPG concentration to accurately assess their future risk for T2DM, as well as their risk for CVD to identify the subgroup of IFG who are at greater risk and subject them to an intervention program to decrease their future T2DM and CVD risk.
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Affiliation(s)
- Muhammad Abdul-Ghani
- aDivision of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA bDepartment of Medicine, Diabetes and Obesity Clinical Research Center, Hamad General Hospital, Doha, Qatar
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25
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Guclu M, Ali A, Eroglu DU, Büyükuysal SO, Cander S, Ocak N. Serum Levels of sRAGE Are Associated with Body Measurements, but Not Glycemic Parameters in Patients with Prediabetes. Metab Syndr Relat Disord 2016; 14:33-9. [DOI: 10.1089/met.2015.0078] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Affiliation(s)
- Metin Guclu
- Department of Endocrinology and Metabolism, Sevket Yilmaz Research and Training Hospital-Bursa, Bursa, Turkey
| | - Asuman Ali
- Department of Neurology, Sevket Yilmaz Research and Training Hospital-Bursa, Bursa, Turkey
| | - Derya Ustun Eroglu
- Department of Internal Medicine, Sevket Yilmaz Research and Training Hospital-Bursa, Bursa, Turkey
| | - Sema Oral Büyükuysal
- Department of Biochemistry, Sevket Yilmaz Research and Training Hospital-Bursa, Bursa, Turkey
| | - Soner Cander
- Department of Endocrinology and Metabolism, Sevket Yilmaz Research and Training Hospital-Bursa, Bursa, Turkey
| | - Nihal Ocak
- Department of Biochemistry, Sevket Yilmaz Research and Training Hospital-Bursa, Bursa, Turkey
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26
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Davis RH, Miller EA, Zhang RZ, Swoboda KJ. Responses to Fasting and Glucose Loading in a Cohort of Well Children with Spinal Muscular Atrophy Type II. J Pediatr 2015; 167:1362-8.e1. [PMID: 26454573 PMCID: PMC7599085 DOI: 10.1016/j.jpeds.2015.09.023] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 07/27/2015] [Accepted: 09/03/2015] [Indexed: 12/30/2022]
Abstract
OBJECTIVE To examine the impact of fasting and glucose tolerance on selected metabolic variables in children with spinal muscular atrophy (SMA) type II in a well state, secondary to reports of glucose regulation abnormalities in SMA. STUDY DESIGN In this prospective pilot study, 6 children aged 7-11 years with SMA type II participated in an oral glucose tolerance test and a supervised medical fast during 2 overnight visits at the University of Utah. At baseline, a dual-energy x-ray absorptiometry scan was performed to determine body composition. Laboratory test results were obtained at baseline and in response to the respective interventions. Data analysis was descriptive. Prefasting and postfasting data were evaluated using the Wilcoxon signed-rank test. RESULTS Based on the dual-energy x-ray absorptiometry scan, all 6 children were variably obese at baseline. All 6 exhibited hyperinsulinemia, and 3 of 6 met formal American Diabetes Association criteria for impaired glucose tolerance. According to homeostatic insulin resistance calculations, 5 of the 6 participants were insulin-resistant. All 6 participants tolerated a monitored fast for 20 hours without hypoglycemia (blood glucose <54 mg/dL). Free fatty acid levels increased significantly from prefasting to postfasting, whereas levels of several plasma amino acids decreased significantly during fasting. CONCLUSION Children with SMA type II defined as obese using objective variables are at increased risk for impaired glucose tolerance regardless of whether or not they visually appear obese. Further studies are needed to determine the prevalence of impaired glucose tolerance and tolerance for fasting within the broader heterogeneous SMA population and to develop appropriate guidelines for intervention.
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Affiliation(s)
- Rebecca Hurst Davis
- Originally affiliated with University of Utah, Department of Neurology Pediatric Motor Disorders Research Program and Division of Nutrition; University of Utah, Division of Nutrition, 30 North 1900 East SOM 3R149, Salt Lake City, UT 84132, Phone: 801-585-1499, Fax: 801-587-9346, Currently affiliated with Intermountain Healthcare, Salt Lake City, UT
| | - Elizabeth A. Miller
- Originally affiliated with University of Utah, Department of Neurology Pediatric Motor Disorders Research Program, Salt Lake City, UT, Currently affiliated with Shriner’s Children’s Hospital, Salt Lake City, UT
| | - Ren Zhe Zhang
- Originally affiliated with University of Utah, Department of Neurology Pediatric Motor Disorders Research Program, Salt Lake City, UT., Currently affiliated with Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA
| | - Kathryn J. Swoboda
- Center for Human Genetics Research, Department of Neurology, Massachusetts General Hospital, 185 Cambridge, Simches 5-238, Boston, MA 02114
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27
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Herder C, Bongaerts BWC, Ouwens DM, Rathmann W, Heier M, Carstensen-Kirberg M, Koenig W, Thorand B, Roden M, Meisinger C, Ziegler D. Low serum omentin levels in the elderly population with Type 2 diabetes and polyneuropathy. Diabet Med 2015; 32:1479-83. [PMID: 26094489 DOI: 10.1111/dme.12761] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/24/2015] [Indexed: 12/21/2022]
Abstract
AIMS To investigate the hypothesis that high serum levels of omentin, an adipokine with anti-inflammatory, insulin-sensitizing and cardioprotective properties, may be related to a lower risk of diabetic sensorimotor polyneuropathy. METHODS The association between serum omentin level and polyneuropathy was estimated in people aged 61-82 years with Type 2 diabetes (47 with and 168 without polyneuropathy) from the population-based KORA F4 study. The presence of clinical diabetic sensorimotor polyneuropathy was defined as bilateral impairment of foot vibration perception and/or foot pressure sensation. Omentin levels were determined by enzyme-linked immunosorbent assay. RESULTS Serum omentin level was inversely associated with polyneuropathy after adjustment for age, sex, height, waist circumference, hypertension, total cholesterol, smoking, alcohol intake and physical activity [odds ratio 0.45 (95% CI 0.21-0.98); P = 0.043]. Although omentin was positively correlated with adiponectin (r = 0.55, P < 0.0001) and inversely with tumour necrosis factor-α (r = -0.30, P = 0.019), additional adjustment for adiponectin and tumour necrosis factor-α had little impact on the association. CONCLUSIONS Serum levels of omentin are reduced in people with Type 2 diabetes and diabetic sensorimotor polyneuropathy, independently of established risk factors of polyneuropathy. This association is only partially explained by biomarkers of subclinical inflammation.
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Affiliation(s)
- C Herder
- Institute for Clinical Diabetology, German Diabetes Centre, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Centre for Diabetes Research (DZD e.V.), Partner Düsseldorf, Germany
| | - B W C Bongaerts
- Institute for Biometrics and Epidemiology, German Diabetes Centre, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - D M Ouwens
- German Centre for Diabetes Research (DZD e.V.), Partner Düsseldorf, Germany
- Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Centre, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium, Germany
| | - W Rathmann
- Institute for Biometrics and Epidemiology, German Diabetes Centre, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - M Heier
- Institute of Epidemiology II, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany
| | - M Carstensen-Kirberg
- Institute for Clinical Diabetology, German Diabetes Centre, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Centre for Diabetes Research (DZD e.V.), Partner Düsseldorf, Germany
| | - W Koenig
- Department of Internal Medicine II - Cardiology, University of Ulm Medical Center, Ulm, Germany
| | - B Thorand
- Institute of Epidemiology II, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany
- German Centre for Diabetes Research (DZD e.V.), Partner Neuherberg, Neuherberg, Germany
| | - M Roden
- Institute for Clinical Diabetology, German Diabetes Centre, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Centre for Diabetes Research (DZD e.V.), Partner Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - C Meisinger
- Institute of Epidemiology II, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany
| | - D Ziegler
- Institute for Clinical Diabetology, German Diabetes Centre, Leibniz Centre for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Centre for Diabetes Research (DZD e.V.), Partner Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
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Boehme MWJ, Buechele G, Frankenhauser-Mannuss J, Mueller J, Lump D, Boehm BO, Rothenbacher D. Prevalence, incidence and concomitant co-morbidities of type 2 diabetes mellitus in South Western Germany--a retrospective cohort and case control study in claims data of a large statutory health insurance. BMC Public Health 2015; 15:855. [PMID: 26334523 PMCID: PMC4559219 DOI: 10.1186/s12889-015-2188-1] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Accepted: 08/26/2015] [Indexed: 12/25/2022] Open
Abstract
Background Type 2 diabetes mellitus (T2DM) has become a world-wide epidemic. This chronic metabolic disease has a major impact on life expectancy and on quality of life. The burden of this disease includes a number of co-morbidities. However, estimates of prevalence, incidence and associated diseases as well as the current temporal development and regional differences are largely missing for South Western Germany. Methods Lifetime diagnosis-based prevalence, incidence and presence of concomitant co-morbidities were examined between the years 2007 and 2010 in the claims data set of all insured persons of the AOK Baden-Wuerttemberg, a large statutory health insurance. The analysis was based on the respective WHO-ICD-10 codes. Data were standardized for age and sex on the residential population of about 10 million inhabitants of South Western Germany. Results The total study cohort involved approximately 3.5 million persons each year. The standardized diagnosis-based prevalence (SDP) of T2DM rose from 6.6 %, 7.4 %, 8.0 %, up to 8.6 % in the years 2007 to 2010. Yearly SDP was between 14.0 % and 18.9 % at an age range of 60 to 64 years and between 26.7 % and 31.8 % at an age of 75 years or older. In the year 2010 the regional distributions of standardized diagnosis-based prevalence were between 7.6 % and 11.6 %, respectively. Incidence rates were 8.3 in 2008, 7.8 in 2009, and 8.7 in 2010 (all rates per 1000). The excess disease risk (odds ratio) of T2DM was for adiposity 2.8 to 3.0, hypertension 2.4 to 3.7, coronary heart disease 1.8 to 1.9, stroke 1.7 to 1.8, renal insufficiency 2.8 to 3.4, and retinopathy 2.8 to 2.9 in the years 2007 to 2010. These co-morbidities appeared several years earlier compared to the non-diabetic population. Conclusions T2DM is common and increasing in South Western Germany. In particular a quarter of the population in higher ages was afflicted by T2DM. Interestingly a region-specific pattern was observed as well as an increase in numbers during earlier years in life. Our data underline the need for diabetes awareness programmes including early diagnosis measures as well as structured and timely health surveys for major diseases such as T2DM and its concomitant co-morbidities. Electronic supplementary material The online version of this article (doi:10.1186/s12889-015-2188-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Michael W J Boehme
- State Health Office Baden-Wuerttemberg - Landesgesundheitsamt Baden-Württemberg im Regierungspräsidium Stuttgart, Nordbahnhofstrasse 135, D-70191, Stuttgart, Germany.
| | - Gisela Buechele
- Institute of Epidemiology and Medical Biometry, Ulm University, Helmholtzstrasse 22, D-89081, Ulm, Germany.
| | | | - Jana Mueller
- State Health Office Baden-Wuerttemberg - Landesgesundheitsamt Baden-Württemberg im Regierungspräsidium Stuttgart, Nordbahnhofstrasse 135, D-70191, Stuttgart, Germany.
| | - Dietlinde Lump
- AOK - Allgemeine Ortskrankenkasse Baden-Württemberg, Presselstraße 19, D-70191, Stuttgart, Germany.
| | - Bernhard O Boehm
- Division of Endocrinology and Diabetes, Ulm University Medical Centre, Ulm University, Albert-Einstein-Allee 23, D-89081, Ulm, Germany. .,LKC School of Medicine, Metabolic Disease Research Program, Nanyang Technological University Singapore and Imperial College London, 50 Nanyang Drive, Research Techno Plaza, X-Frontiers Block, Singapore, 637553, Singapore.
| | - Dietrich Rothenbacher
- Institute of Epidemiology and Medical Biometry, Ulm University, Helmholtzstrasse 22, D-89081, Ulm, Germany.
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Papanas N, Ziegler D. Risk Factors and Comorbidities in Diabetic Neuropathy: An Update 2015. Rev Diabet Stud 2015; 12:48-62. [PMID: 26676661 PMCID: PMC5397983 DOI: 10.1900/rds.2015.12.48] [Citation(s) in RCA: 129] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 04/27/2015] [Accepted: 05/07/2015] [Indexed: 01/01/2023] Open
Abstract
Distal symmetric sensorimotor polyneuropathy (DSPN) is the most common neurological manifestation in diabetes. Major risk factors of DSPN include diabetes duration, hyperglycemia, and age, followed by prediabetes, hypertension, dyslipidemia, and obesity. Height, smoking, insulin resistance, hypoinsulinemia, and others represent an additional risk. Importantly, hyperglycemia, hypertension, dyslipidemia, obesity, and smoking are modifiable. Stringent glycemic control has been shown to be effective in type 1, but not to the same extent in type 2 diabetes. Antilipidemic treatment, especially with fenofibrate, and multi-factorial intervention have produced encouraging results, but more experience is necessary. The major comorbidities of DSPN are depression, autonomic neuropathy, peripheral arterial disease, cardiovascular disease, nephropathy, retinopathy, and medial arterial calcification. Knowledge of risk factors and comorbidities has the potential to enrich the therapeutic strategy in clinical practice as part of the overall medical care for patients with neuropathy. This article provides an updated overview of DSPN risk factors and comorbidities.
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Affiliation(s)
- Nikolaos Papanas
- Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
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Abstract
Patients suffering from DN (diabetic neuropathy) suffer from the coexistence of positive (i.e. pain, hypersensitivity, tingling, cramps, cold feet, etc.) and negative (i.e. loss of sensory perception, delayed wound healing, etc.) symptoms. Elevated blood glucose alone cannot explain the development and progression of DN. Recently it has been shown that the endogenous reactive metabolite MG (methylglyoxal), elevated as a consequence of reduced Glo1 (glyoxalase I), can contribute to the gain of function via post-translational modification of neuronal ion channels involved in chemosensing and action potential generation in nociceptive nerve endings. The effects of dicarbonyls on the neuronal compartment provides a unifying mechanism for the development of DN. Targeting the accumulation and effects of MG may therefore provide new, more effective, therapeutic approaches for the treatment of DN.
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Abstract
Distal symmetric polyneuropathy (DSPN), the most common form of diabetic neuropathy, has a complex pathophysiology and can be a major source of physical and psychologic disability. The management of DSPN can be frustrating for both patient and physician. This article provides a general overview of typical patient pathways in DSPN, and highlights variations in diagnosis, management, and referral patterns among different providers. DSPN is managed in several settings by primary care physicians (PCPs), specialists, and nurse practitioners. The initial clinical management of the patient is often dependent on the presenting complaint, the referral pattern of the provider, level of comfort of the PCP in managing diabetic complications, and geographic access to specialists. The primary treatment of DSPN focuses mainly on glycemic control and adjustment of modifiable risk factors, but other causes of neuropathy should also be investigated. Several pharmacologic agents are recommended by treatment guidelines, and as DSPN typically exists with comorbid conditions, a multimodal therapeutic approach should be considered. Barriers to effective management include failure to recognize DSPN, and misdiagnosis. Patient education also remains important. Referral patterns vary widely according to geographic location, access to services, provider preferences, and comfort in managing complex aspects of the disease. The variability in patient pathways affects patient education, satisfaction, and outcomes. Standardized screening tools, a multidisciplinary team approach, and treatment algorithms for diabetic neuropathy should improve future care. To improve patient outcomes, DSPN needs to be diagnosed sooner and interventions made before significant nerve damage occurs.
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Affiliation(s)
- Michelle Kaku
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Kassardjian CD, Dyck PJB, Davies JL, Carter RE, Dyck PJ. Does prediabetes cause small fiber sensory polyneuropathy? Does it matter? J Neurol Sci 2015; 355:196-8. [PMID: 26049659 DOI: 10.1016/j.jns.2015.05.026] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 05/18/2015] [Accepted: 05/19/2015] [Indexed: 01/14/2023]
Abstract
BACKGROUND AND OBJECTIVES The association between prediabetes and distal polyneuropathy (DPN) remains controversial. Here we test whether the prevalence of small fiber sensory distal polyneuropathy is increased in prediabetes. METHODS Prospectively recruited cohorts of healthy subjects and those with prediabetes from Olmsted County, Minnesota, were assessed for positive neuropathic sensory symptoms, or pain symptoms characteristic of small fiber sensory DPN. Hyperalgesia and hypoalgesia were assessed by "smart" quantitative sensation testing (QST). The prevalence of symptoms and QST abnormalities were compared among the groups. RESULTS There was no significant increase in the prevalence of positive neuropathic sensory or pain symptoms, nor of hyper- or hypoalgesia in the prediabetes group. There was an increased prevalence of hypoalgesia of the foot only in newly diagnosed diabetes. CONCLUSIONS Based on positive sensory and pain symptoms and QSTs, we did not find an increase in small fiber sensory DPN in prediabetes. Recognizing that obesity and diabetes mellitus are implicated in macro- and microvessel complications, physicians should encourage healthy living and weight loss in patients with prediabetes. In medical practice, alternate causes should be excluded before concluding that small fiber sensory distal neuropathy is secondary to prediabetes.
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Affiliation(s)
- C D Kassardjian
- Peripheral Neuropathy Research Laboratory, Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - P J B Dyck
- Peripheral Neuropathy Research Laboratory, Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - J L Davies
- Peripheral Neuropathy Research Laboratory, Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Rickey E Carter
- Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - P J Dyck
- Peripheral Neuropathy Research Laboratory, Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
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Lee CC, Perkins BA, Kayaniyil S, Harris SB, Retnakaran R, Gerstein HC, Zinman B, Hanley AJ. Peripheral Neuropathy and Nerve Dysfunction in Individuals at High Risk for Type 2 Diabetes: The PROMISE Cohort. Diabetes Care 2015; 38:793-800. [PMID: 25665810 DOI: 10.2337/dc14-2585] [Citation(s) in RCA: 93] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2014] [Accepted: 01/05/2015] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Emerging evidence suggests that peripheral neuropathy begins in the early stages of diabetes pathogenesis. Our objective was to describe the prevalence of peripheral neuropathy and nerve dysfunction according to glucose tolerance and metabolic syndrome status and examine how these conditions are associated with neurological changes in individuals at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS We studied 467 individuals in the longitudinal PROMISE (Prospective Metabolism and Islet Cell Evaluation) cohort. Peripheral neuropathy was defined by Michigan Neuropathy Screening Instrument (MNSI) scores (>2), and the severity of nerve dysfunction was measured objectively by vibration perception thresholds (VPTs) using a neurothesiometer. Metabolic syndrome was defined using the International Diabetes Federation/American Heart Association harmonized criteria. RESULTS The prevalence of peripheral neuropathy was 29%, 49%, and 50% for normal glycemia, prediabetes, and new-onset diabetes, respectively (P < 0.001 for trend). The mean VPT was 6.5 V for normal glycemia, 7.9 V for prediabetes, and 7.6 V for new-onset diabetes (P = 0.024 for trend). Prediabetes was associated with higher MNSI scores (P = 0.01) and VPTs (P = 0.004) versus normal glycemia, independent of known risk factors. Additionally, progression of glucose intolerance over 3 years predicted a higher risk of peripheral neuropathy (P = 0.007) and nerve dysfunction (P = 0.002). Metabolic syndrome was not independently associated with MNSI scores or VPTs. CONCLUSIONS In individuals with multiple risk factors for diabetes, prediabetes was associated with similar risks of peripheral neuropathy and severity of nerve dysfunction as new-onset diabetes. Prediabetes, but not metabolic syndrome, was independently associated with both the presence of peripheral neuropathy and the severity of nerve dysfunction.
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Affiliation(s)
- C Christine Lee
- Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada
| | - Bruce A Perkins
- Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Sheena Kayaniyil
- Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada
| | - Stewart B Harris
- Centre for Studies in Family Medicine, University of Western Ontario, London, ON, Canada
| | - Ravi Retnakaran
- Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, ON, Canada Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
| | - Hertzel C Gerstein
- Division of Endocrinology and Metabolism and the Population Health Research Institute, Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Bernard Zinman
- Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, ON, Canada Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
| | - Anthony J Hanley
- Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, ON, Canada Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
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Herder C, Bongaerts BWC, Rathmann W, Heier M, Kowall B, Koenig W, Thorand B, Roden M, Meisinger C, Ziegler D. Differential association between biomarkers of subclinical inflammation and painful polyneuropathy: results from the KORA F4 study. Diabetes Care 2015; 38:91-6. [PMID: 25325880 DOI: 10.2337/dc14-1403] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Inflammatory processes have been implicated in the pathogenesis of painful neuropathy in rodents, but the relationship between inflammatory biomarkers and painful distal sensorimotor polyneuropathy (DSPN) has not been assessed in population-based studies. Therefore, we investigated whether circulating levels of seven pro- and anti-inflammatory immune mediators were associated with painful DSPN in older individuals in a large population-based study. RESEARCH DESIGN AND METHODS The study population consisted of individuals with painless (n = 337) and painful DSPN (n = 54) from a source population (n = 1,047) of men and women aged 61-82 years who participated in the German KORA F4 survey (2006-2008). We measured circulating levels of seven immune mediators and assessed their associations with the presence of painful DSPN using multiple logistic regression models. RESULTS After adjustment for age and sex, we found positive associations between serum concentrations of the cytokine interleukin (IL)-6 and the soluble intercellular adhesion molecule (sICAM)-1 and painful DSPN (P = 0.004 and P = 0.005, respectively), whereas no associations were observed for C-reactive protein, IL-18, tumor necrosis factor-α, adiponectin, and IL-1 receptor antagonist (IL-1RA, P = 0.07-0.38). Associations between IL-6 and sICAM-1 and painful DSPN remained significant after additional adjustment for waist circumference, height, hypertension, cholesterol, smoking, alcohol intake, physical activity, history of myocardial infarction and/or stroke, presence of other neurological conditions, and use of nonsteroidal anti-inflammatory drugs (P = 0.005 and P = 0.016, respectively). CONCLUSIONS Painful DSPN is linked to systemic subclinical and vascular inflammation in the older population independent of anthropometric, lifestyle, and metabolic confounders.
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Affiliation(s)
- Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes Research (DZD), Düsseldorf, Germany
| | - Brenda W C Bongaerts
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Wolfgang Rathmann
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Margit Heier
- Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Bernd Kowall
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Wolfgang Koenig
- Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany
| | - Barbara Thorand
- Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes Research (DZD), Düsseldorf, Germany Department of Endocrinology and Diabetology, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Christa Meisinger
- Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes Research (DZD), Düsseldorf, Germany Department of Endocrinology and Diabetology, University Hospital Düsseldorf, Düsseldorf, Germany
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Bongaerts BWC, Ziegler D, Shaw JE, Heier M, Kowall B, Herder C, Roden M, Peters A, Meisinger C, Rathmann W. A clinical screening score for diabetic polyneuropathy: KORA F4 and AusDiab studies. J Diabetes Complications 2015; 29:44-9. [PMID: 25457462 DOI: 10.1016/j.jdiacomp.2014.09.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 09/29/2014] [Accepted: 09/30/2014] [Indexed: 11/21/2022]
Abstract
AIMS Since screening for distal sensorimotor polyneuropathy (DSPN) in individuals with diabetes is being underused, our aim was to develop a clinical screening score for identifying individuals with DSPN. METHODS All participants with type 2 diabetes and aged 61-82 years from the German population-based KORA F4 Study (n=177) and the Australian population-based AusDiab Study (n=244) were combined into one study sample. Risk indicators of DSPN were identified and entered into a stepwise model-selection procedure, constructing two consecutive scores with increasing complexity (a base and clinical model). RESULTS The prevalence of DSPN was 18.2% (95% confidence interval (CI): 14.7-22.3). The base model comprised age (years), height (cm), weight (kg), pain or discomfort in the feet and/or legs (yes/no), and duration of diabetes (years), yielding an area under the receiver operating characteristics curve (AUC) of 0.80 (95% CI: 0.76-0.85). The clinical model additionally included diastolic blood pressure (mmHg) and serum creatinine levels (mmol/l). The AUC increased only marginally to 0.82 (0.77-0.87) (p for AUC comparison=0.188). The internal validation of the scores produced similar AUCs. CONCLUSIONS The screening scores developed in this study are a simple tool to differentiate between a high and low likelihood of having DSPN among individuals with type 2 diabetes.
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Affiliation(s)
- B W C Bongaerts
- Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf´m Hennekamp 65, 40225 Düsseldorf, Germany.
| | - D Ziegler
- Department of Endocrinology and Diabetology, University Hospital Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf´m Hennekamp 65, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), partner Düsseldorf, Auf´m Hennekamp 65, 40225 Germany
| | - J E Shaw
- Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, Victoria 3004, Australia
| | - M Heier
- Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
| | - B Kowall
- Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf´m Hennekamp 65, 40225 Düsseldorf, Germany
| | - C Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf´m Hennekamp 65, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), partner Düsseldorf, Auf´m Hennekamp 65, 40225 Germany
| | - M Roden
- Department of Endocrinology and Diabetology, University Hospital Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf´m Hennekamp 65, 40225 Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), partner Düsseldorf, Auf´m Hennekamp 65, 40225 Germany
| | - A Peters
- Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
| | - C Meisinger
- Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
| | - W Rathmann
- Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf´m Hennekamp 65, 40225 Düsseldorf, Germany
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Tamayo T, Schipf S, Meisinger C, Schunk M, Maier W, Herder C, Roden M, Nauck M, Peters A, Völzke H, Rathmann W. Regional differences of undiagnosed type 2 diabetes and prediabetes prevalence are not explained by known risk factors. PLoS One 2014; 9:e113154. [PMID: 25402347 PMCID: PMC4234669 DOI: 10.1371/journal.pone.0113154] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Accepted: 10/20/2014] [Indexed: 01/15/2023] Open
Abstract
Background We have previously found regional differences in the prevalence of known type 2 diabetes between northeastern and southern Germany. We aim to also provide prevalence estimates for prediabetes (isolated impaired fasting glucose (i-IFG), isolated glucose intolerance (i-IGT), combined IFG and IGT) and unknown type 2 diabetes for both regions. Methods Prevalence (95%CI) of prediabetes (i-IFG: fasting glucose 5.6–6.9 mmol/l; i-IGT: 2 h postchallenge gluose 7.8–11.0 mmol/l, oral glucose tolerance test (OGTT), ≥8 h overnight fasting) and unknown diabetes were analyzed in two regional population-based surveys (age group 35–79 years): SHIP-TREND (Study of Health in Pomerania (northeast), 2008–2012) and KORA F4 (Cooperative Health Research in the region of Augsburg (south), 2006–2008). Both studies used similar methods, questionnaires, and identical protocols for OGTT. Overall, 1,980 participants from SHIP-TREND and 2,617 participants from KORA F4 were included. Results Age-sex-standardized prevalence estimates (95%CI) of prediabetes and unknown diabetes were considerably higher in the northeast (SHIP-TREND: 43.1%; 40.9–45.3% and 7.1%; 5.9–8.2%) than in the south of Germany (KORA F4: 30.1%; 28.4–31.7% and 3.9%; 3.2–4.6%), respectively. In particular, i-IFG (26.4%; 24.5–28.3% vs. 17.2%; 15.7–18.6%) and IFG+IGT (11.2%; 9.8–12.6% vs. 6.6%; 5.7–7.5%) were more frequent in SHIP-TREND than in KORA. In comparison to normal glucose tolerance, the odds of having unknown diabetes (OR, 95%CI: 2.59; 1.84–3.65) or prediabetes (1.98; 1.70–2.31) was higher in the northeast than in the south after adjustment for known risk factors (obesity, lifestyle). Conclusions The regional differences of prediabetes and unknown diabetes are in line with the geographical pattern of known diabetes in Germany. The higher prevalences in the northeast were not explained by traditional risk factors.
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Affiliation(s)
- Teresa Tamayo
- Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf, Germany
- Competence Network Diabetes mellitus (Federal Ministry of Education and Research, Germany), Sites Düsseldorf, Munich and Greifswald, Germany
- * E-mail:
| | - Sabine Schipf
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
- Competence Network Diabetes mellitus (Federal Ministry of Education and Research, Germany), Sites Düsseldorf, Munich and Greifswald, Germany
| | - Christine Meisinger
- Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Neuherberg, Germany
- Competence Network Diabetes mellitus (Federal Ministry of Education and Research, Germany), Sites Düsseldorf, Munich and Greifswald, Germany
| | - Michaela Schunk
- Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Health Economics and Health Care Management, Neuherberg, Germany
- Competence Network Diabetes mellitus (Federal Ministry of Education and Research, Germany), Sites Düsseldorf, Munich and Greifswald, Germany
| | - Werner Maier
- Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Health Economics and Health Care Management, Neuherberg, Germany
- Competence Network Diabetes mellitus (Federal Ministry of Education and Research, Germany), Sites Düsseldorf, Munich and Greifswald, Germany
| | - Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD e.V.), Sites Düsseldorf and Munich, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, University Hospital Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD e.V.), Sites Düsseldorf and Munich, Germany
| | - Matthias Nauck
- Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
- Competence Network Diabetes mellitus (Federal Ministry of Education and Research, Germany), Sites Düsseldorf, Munich and Greifswald, Germany
| | - Annette Peters
- Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Neuherberg, Germany
- German Center for Diabetes Research (DZD e.V.), Sites Düsseldorf and Munich, Germany
- German Center of Cardiovascular Research (DZHK e.V.), Sites Munich and Greifswald, Germany
| | - Henry Völzke
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
- German Center of Cardiovascular Research (DZHK e.V.), Sites Munich and Greifswald, Germany
- Competence Network Diabetes mellitus (Federal Ministry of Education and Research, Germany), Sites Düsseldorf, Munich and Greifswald, Germany
| | - Wolfgang Rathmann
- Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University, Düsseldorf, Germany
- Competence Network Diabetes mellitus (Federal Ministry of Education and Research, Germany), Sites Düsseldorf, Munich and Greifswald, Germany
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Kostev K, Jockwig A, Hallwachs A, Rathmann W. Prevalence and risk factors of neuropathy in newly diagnosed type 2 diabetes in primary care practices: a retrospective database analysis in Germany and U.K. Prim Care Diabetes 2014; 8:250-255. [PMID: 24530101 DOI: 10.1016/j.pcd.2014.01.011] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Revised: 11/27/2013] [Accepted: 01/18/2014] [Indexed: 12/01/2022]
Abstract
AIMS To estimate the prevalence and risk factors of diabetic neuropathy in newly diagnosed type 2 diabetes in general practices. METHODS Longitudinal data from nationwide general practices in Germany (n=630) and U.K. (n=100) (Disease Analyzer) were analyzed. Patients with newly diagnosed (<1 year) type 2 diabetes (2008-2012) were identified including 45,633 patients (age: 66, SD: 12 years) in Germany and 14,205 patients (age: 63, SD: 13 years) in U.K. Neuropathy was identified by ICD code (E11.4) or the original diagnosis. Associations of potential risk factors with neuropathy were investigated using logistic regression. RESULTS The prevalence of diagnosed neuropathy was 5.7% (95% CI: 5.5-5.9%) in Germany and 2.4% (1.9-2.9%) in U.K. In Germany, factors independently associated with neuropathy in stepwise logistic regression were age (>70 years: OR; 95% CI 2.1; 1.6-2.8), retinopathy (3.0; 2.1-4.2), peripheral artery disease (PAD: 1.9; 1.4-2.5), insulin treatment (4.6; 3.5-6.2) and oral antidiabetic drugs (OAD: 1.6; 1.2-2.0). In UK, male sex (1.4; 1.01-1.9), nephropathy (1.7; 1.2-2.5), PAD (1.5; 1.1-2.1), antihypertensives (1.7; 1.1-2.5), insulin (2.1; 1.1-3.8) and OAD (1.4; 1.01-1.8) were identified. CONCLUSIONS The prevalence of diabetic neuropathy at time of type 2 diabetes diagnosis was low in primary care (Germany, UK). Neuropathy was associated with age, PAD and microvacular complications.
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Affiliation(s)
| | - Achim Jockwig
- Fresenius University of Applied Sciences, Health & Social Faculty, Germany
| | | | - Wolfgang Rathmann
- Institute of Biometrics and Epidemiology, German Diabetes Center, Duesseldorf, Germany
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Kondo M, Kamiya H, Himeno T, Naruse K, Nakashima E, Watarai A, Shibata T, Tosaki T, Kato J, Okawa T, Hamada Y, Isobe KI, Oiso Y, Nakamura J. Therapeutic efficacy of bone marrow-derived mononuclear cells in diabetic polyneuropathy is impaired with aging or diabetes. J Diabetes Investig 2014; 6:140-9. [PMID: 25802721 PMCID: PMC4364848 DOI: 10.1111/jdi.12272] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Revised: 07/04/2014] [Accepted: 07/27/2014] [Indexed: 12/14/2022] Open
Abstract
Aims/Introduction Recent studies have shown that cell transplantation therapies, such as endothelial precursor cells, bone marrow-derived mononuclear cells (BM-MNCs) and mesenchymal stem cells, are effective on diabetic polyneuropathy through ameliorating impaired nerve blood flow in diabetic rats. Here, we investigated the effects of BM-MNCs transplantation in diabetic polyneuropathy using BM-MNCs derived from adult (16-week-old) diabetic (AD), adult non-diabetic (AN) or young (8-week-old) non-diabetic (YN) rats. Materials and Methods BM-MNCs of AD and AN were isolated after an 8-week diabetes duration. The BM-MNCs were characterized using flow cytometry analysis of cell surface markers and reverse transcription polymerase chain reaction of several cytokines. BM-MNCs or saline were injected into hind limb muscles. Four weeks later, the thermal plantar test, nerve conduction velocity, blood flow of the sciatic nerve and capillary-to-muscle fiber ratio were evaluated. Results The number of CD29+/CD90+ cells that host mesenchymal stem cells in BM-MNCs decreased in AD compared with AN or YN, and transcript expressions of basic fibroblast growth factor and nerve growth factor in BM-MNCs decreased in AD compared with AN or YN. Impaired thermal sensation, decreased blood flow of the sciatic nerve and delayed nerve conduction velocity in 8-week-diabetic rats were significantly ameliorated by BM-MNCs derived from YN, whereas BM-MNCs from AD or AN rats did not show any beneficial effect in these functional tests. Conclusions These results show that cytokine production abilities and the mesenchymal stem cell population of BM-MNCs would be modified by aging and metabolic changes in diabetes, and that these differences could explain the disparity of the therapeutic efficacy of BM-MNCs between young and adult or diabetic and non-diabetic patients in diabetic polyneuropathy.
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Affiliation(s)
- Masaki Kondo
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan ; Department of Immunology, Nagoya University Graduate School of Medicine Nagoya, Japan
| | - Hideki Kamiya
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan ; Department of CKD Initiatives, Nagoya University Graduate School of Medicine Nagoya, Japan
| | - Tatsuhito Himeno
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan
| | - Keiko Naruse
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan
| | - Eitaro Nakashima
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan
| | - Atsuko Watarai
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan
| | - Taiga Shibata
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan
| | - Takahiro Tosaki
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan
| | - Jiro Kato
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan
| | - Tetsuji Okawa
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan
| | - Yoji Hamada
- Department of Metabolic Medicine, Nagoya University Graduate School of Medicine Nagoya, Japan
| | - Ken-Ichi Isobe
- Department of Immunology, Nagoya University Graduate School of Medicine Nagoya, Japan
| | - Yutaka Oiso
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan
| | - Jiro Nakamura
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Nagoya, Japan
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Ziegler D, Papanas N, Zhivov A, Allgeier S, Winter K, Ziegler I, Brüggemann J, Strom A, Peschel S, Köhler B, Stachs O, Guthoff RF, Roden M. Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes. Diabetes 2014; 63:2454-63. [PMID: 24574045 DOI: 10.2337/db13-1819] [Citation(s) in RCA: 239] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
We sought to determine whether early nerve damage may be detected by corneal confocal microscopy (CCM), skin biopsy, and neurophysiological tests in 86 recently diagnosed type 2 diabetic patients compared with 48 control subjects. CCM analysis using novel algorithms to reconstruct nerve fiber images was performed for all fibers and major nerve fibers (MNF) only. Intraepidermal nerve fiber density (IENFD) was assessed in skin specimens. Neurophysiological measures included nerve conduction studies (NCS), quantitative sensory testing (QST), and cardiovascular autonomic function tests (AFTs). Compared with control subjects, diabetic patients exhibited significantly reduced corneal nerve fiber length (CNFL-MNF), fiber density (CNFD-MNF), branch density (CNBD-MNF), connecting points (CNCP), IENFD, NCS, QST, and AFTs. CNFD-MNF and IENFD were reduced below the 2.5th percentile in 21% and 14% of the diabetic patients, respectively. However, the vast majority of patients with abnormal CNFD showed concomitantly normal IENFD and vice versa. In conclusion, CCM and skin biopsy both detect nerve fiber loss in recently diagnosed type 2 diabetes, but largely in different patients, suggesting a patchy manifestation pattern of small fiber neuropathy. Concomitant NCS impairment points to an early parallel involvement of small and large fibers, but the precise temporal sequence should be clarified in prospective studies.
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Affiliation(s)
- Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, GermanyDepartment of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany
| | - Nikolaos Papanas
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
| | - Andrey Zhivov
- Department of Ophthalmology, University of Rostock, Rostock, Germany
| | - Stephan Allgeier
- Institute for Applied Computer Science and Automation, Karlsruhe Institute of Technology, Karlsruhe, Germany
| | - Karsten Winter
- Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany
| | - Iris Ziegler
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
| | - Jutta Brüggemann
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
| | - Alexander Strom
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
| | - Sabine Peschel
- Department of Ophthalmology, University of Rostock, Rostock, Germany
| | - Bernd Köhler
- Institute for Applied Computer Science, Karlsruhe Institute of Technology, Karlsruhe, Germany
| | - Oliver Stachs
- Department of Ophthalmology, University of Rostock, Rostock, Germany
| | - Rudolf F Guthoff
- Department of Ophthalmology, University of Rostock, Rostock, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, GermanyDepartment of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany
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Tamayo T, Rosenbauer J, Wild SH, Spijkerman AMW, Baan C, Forouhi NG, Herder C, Rathmann W. Diabetes in Europe: an update. Diabetes Res Clin Pract 2014; 103:206-17. [PMID: 24300019 DOI: 10.1016/j.diabres.2013.11.007] [Citation(s) in RCA: 161] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Diabetes is among the leading causes of death in the IDF Europe Region (EUR), continues to increase in prevalence with diabetic macro- and microvascular complications resulting in increased disability and enormous healthcare costs. In 2013, the number of people with diabetes is estimated to be 56 million in EUR with an overall estimated prevalence of 8.5%. However, estimates of diabetes prevalence in 2013 vary widely in the 56 diverse countries in EUR from 2.4% in Moldova to 14.9% in Turkey. Trends in diabetes prevalence also vary between countries with stable prevalence since 2002 for many countries but a doubling of diabetes prevalence in Turkey. For 2035, a further increase of nearly 10 million people with diabetes is projected for the EUR. Prevalence of type 1 has also increased over the past 20 years in EUR and there was estimated to be 129,350 cases in children aged 0-14 years in 2013. Registries provide valid information on incidence of type 1 diabetes with more complete data available for children than for adults. There are large differences in distribution of risk factors for diabetes at the population level in EUR. Modifiable risk factors such as obesity, physical inactivity, smoking behaviour (including secondhand smoking), environmental pollutants, psychosocial factors and socioeconomic deprivation could be tackled to reduce the incidence of type 2 diabetes in Europe. In addition, diabetes management is a major challenge to health services in the European countries. Improved networking practices of health professionals and other stakeholders in combination with empowerment of people with diabetes and continuous quality monitoring need to be further developed in Europe.
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Affiliation(s)
- T Tamayo
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - J Rosenbauer
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - S H Wild
- Centre for Population Health Sciences, University of Edinburgh, UK
| | - A M W Spijkerman
- Centre for Nutrition, Prevention and Health Services, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands
| | - C Baan
- Centre for Nutrition, Prevention and Health Services, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands
| | - N G Forouhi
- Medical Research Council Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
| | - C Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - W Rathmann
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
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Kowall B, Rathmann W. HbA1c for diagnosis of type 2 diabetes. Is there an optimal cut point to assess high risk of diabetes complications, and how well does the 6.5% cutoff perform? Diabetes Metab Syndr Obes 2013; 6:477-91. [PMID: 24348061 PMCID: PMC3848642 DOI: 10.2147/dmso.s39093] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Glycated hemoglobin (HbA1c) has recently been recommended for the diagnosis of type 2 diabetes mellitus (T2DM) by leading diabetes organizations and by the World Health Organization. The most important reason to define T2DM is to identify subjects with high risk of diabetes complications who may benefit from treatment. This review addresses two questions: 1) to assess from existing studies whether there is an optimal HbA1c threshold to predict diabetes complications and 2) to assess how well the recommended 6.5% cutoff of HbA1c predicts diabetes complications. HbA1c cutoffs derived from predominantly cross-sectional studies on retinopathy differ widely from 5.2%-7.8%, and among other reasons, this is due to the heterogeneity of statistical methods and differences in the definition of retinopathy. From the few studies on other microvascular complications, HbA1c thresholds could not be identified. HbA1c cutoffs make less sense for the prediction of cardiovascular events (CVEs) because CVE risks depend on various strong risk factors (eg, hypertension, smoking); subjects with low HbA1c levels but high values of CVE risk factors were shown to be at higher CVE risk than subjects with high HbA1c levels and low values of CVE risk factors. However, the recommended 6.5% threshold distinguishes well between subjects with and subjects without retinopathy, and this distinction is particularly strong in severe retinopathy. Thus, in existing studies, the prevalence of any retinopathy was 2.5 to 4.5 times as high in persons with HbA1c-defined T2DM as in subjects with HbA1c <6.5%. To conclude, from existing studies, a consistent optimal HbA1c threshold for diabetes complications cannot be derived, and the recommended 6.5% threshold has mainly been brought about by convention rather than by having a consistent empirical basis. Nevertheless, the 6.5% threshold is suitable to detect subjects with prevalent retinopathy, which is the most diabetes specific complication. However, most of the studies on associations between HbA1c and microvascular diabetes complications are cross-sectional, and there is a need for longitudinal studies.
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Affiliation(s)
- Bernd Kowall
- Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Correspondence: Bernd Kowall, Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf’m Hennekamp 65, Düsseldorf 40225, Germany, Tel +49 21 1338 2338, Fax +49 21 1338 2677, Email
| | - Wolfgang Rathmann
- Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
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Herder C, Bongaerts BWC, Rathmann W, Heier M, Kowall B, Koenig W, Thorand B, Roden M, Meisinger C, Ziegler D. Association of subclinical inflammation with polyneuropathy in the older population: KORA F4 study. Diabetes Care 2013; 36:3663-70. [PMID: 24009302 PMCID: PMC3816905 DOI: 10.2337/dc13-0382] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Inflammatory processes have been implicated in the pathogenesis of diabetic distal sensorimotor polyneuropathy (DSPN), but their possible relationship has not been assessed at the population level. RESEARCH DESIGN AND METHODS We determined serum concentrations of mediators of subclinical inflammation among 1,047 participants 61-82 years of age from the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (Germany). Logistic and linear regression models were fitted to assess associations between immune mediators (log-transformed) and the presence of clinical DSPN (dichotomous variable) or Michigan Neuropathy Screening Instrument (MNSI) examination score (continuous variable), respectively. RESULTS Serum concentrations of the anti-inflammatory interleukin (IL)-1 receptor antagonist (IL-1RA) were positively associated with the presence of DSPN and higher MNSI scores in age-adjusted and sex-adjusted analyses, whereas IL-6, IL-18, and soluble intercellular adhesion molecule-1 were positively associated with only MNSI scores. No associations were observed for adiponectin, C-reactive protein, or tumor necrosis factor-α. Associations for IL-1RA and IL-6 with the MNSI score remained statistically significant after additional adjustment for waist circumference, height, hypertension, cholesterol, smoking, alcohol intake, physical activity, history of myocardial infarction or stroke, presence of neurological conditions, and use of nonsteroidal anti-inflammatory drugs. CONCLUSIONS We conclude that DSPN is linked to proinflammatory and anti-inflammatory, possibly compensatory, processes in the older general population. Future studies should clarify the temporal sequence and causality of these associations.
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Lee YJ, Kim NK, Yang JY, Noh JH, Lee SS, Ko KS, Rhee BD, Kim DJ. Low pulmonary function in individuals with impaired fasting glucose: the 2007-2009 Korea national health and nutrition examination survey. PLoS One 2013; 8:e76244. [PMID: 24086719 PMCID: PMC3785444 DOI: 10.1371/journal.pone.0076244] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Accepted: 08/22/2013] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE To investigate the association between fasting plasma glucose level and pulmonary function. RESEARCH DESIGN AND METHODS Nutritional information, pulmonary function data, and laboratory test data from 9,223 subjects from the fourth Korea National Health and Nutrition Examination Survey were examined. The participants were divided into five groups according to fasting plasma glucose (FPG) level: normal fasting glucose (NFG)1, FPG <90 mg/dl; NFG2, FPG 90-99 mg/dl; impaired fasting glucose (IFG)1: FPG 100-109 mg/dl; IFG2, FPG 110-125 mg/dl; and diabetes, FPG ≥126 mg/dl and/or current anti-diabetes medications. RESULTS After adjustment for several variables, the percentage of predicted forced vital capacity(FVC%) decreased with increasing fasting plasma glucose level in both sexes[men: (mean ± SEM) 92.0±0.3 in NFG1; 91.9±0.3 in NFG2; 92.0±0.4 in IFG1; 90.2±0.7 in IFG2; and 89.9±0.5 in diabetes, P = 0.004; women: 93.7±0.3 in NFG1; 93.7±0.3 in NFG2; 93.1±0.5 in IFG1; 91.1±0.9 in IFG2; and 90.7±0.6 in diabetes, P<0.001]. A logistic regression analysis found that IFG2 and diabetes were independently associated with the lowest quintile of predicted FVC% (IFG2: odds ratio [95%CI], 1.50 [1.18-1.89], P = 0.001; diabetes: 1.56 [1.30-1.88], P<0.001) using NFG1 as a control. CONCLUSIONS The current data suggest that forced vital capacity may begin to decrease in the higher range of IFG.
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Affiliation(s)
- Yun Jeong Lee
- Department of Internal Medicine, Inje University College of Medicine, Busan, Korea
| | - Na Kyung Kim
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ju Yean Yang
- Department of Internal Medicine, Inje University College of Medicine, Busan, Korea
| | - Jung Hyun Noh
- Department of Internal Medicine, Inje University College of Medicine, Busan, Korea
| | - Sung-Soon Lee
- Department of Internal Medicine, Inje University College of Medicine, Busan, Korea
| | - Kyung Soo Ko
- Department of Internal Medicine, Inje University College of Medicine, Busan, Korea
| | - Byoung Doo Rhee
- Department of Internal Medicine, Inje University College of Medicine, Busan, Korea
| | - Dong-Jun Kim
- Department of Internal Medicine, Inje University College of Medicine, Busan, Korea
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Færch K, Witte DR, Tabák AG, Perreault L, Herder C, Brunner EJ, Kivimäki M, Vistisen D. Trajectories of cardiometabolic risk factors before diagnosis of three subtypes of type 2 diabetes: a post-hoc analysis of the longitudinal Whitehall II cohort study. Lancet Diabetes Endocrinol 2013; 1:43-51. [PMID: 24622266 DOI: 10.1016/s2213-8587(13)70008-1] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND Most clinicians acknowledge that type 2 diabetes is multifactorial and has heterogeneous characteristics, but neither prevention nor treatment is systematically stratified. To address the heterogeneity of the disease, we examined whether patients diagnosed on the basis of fasting glucose concentrations, those diagnosed on the basis of 2 h concentrations, and those diagnosed on the basis of both criteria differed in terms of pathogenesis or cardiovascular risks. METHODS Retrospectively, we analysed trajectories of cardiometabolic risk factors and 10 year cardiovascular risks in the prospective Whitehall II study cohort by use of multilevel longitudinal modelling. Participants were diagnosed by 75 g oral glucose-tolerance tests. We classified those diagnosed with type 2 diabetes into three subgroups: diagnosed on the basis of fasting glucose concentrations, diagnosed on the basis of 2 h glucose concentrations, and diagnosed on the basis of both concentrations. We also developed a classification tree for identification of individuals who are likely to have high fasting and 2 h glucose concentrations, but for whom only fasting concentrations are available. RESULTS Median follow-up was 14·2 years with 15,826 person-examinations (1991-2009). Of 10,308 individuals, 6843 were included and 6569 remained diabetes free. 274 cases of type 2 diabetes were identified: 55 had high fasting glucose concentrations only, 148 had high 2 h concentrations only, and 71 had high fasting and 2 h concentrations. At diagnosis, participants with high fasting and 2 h glucose concentrations had higher mean body-mass indices (30·9 kg/m(2) [SD 5·7]) than did those with high fasting concentrations (28·4 kg/m(2) [4·4]; p=0·0009) or 2 h concentrations (27·9 kg/m(2) [4·9]; <0·0001). Mean glycated haemoglobin A1c concentrations were also higher in the fasting and 2 h subgroup (7·4% [1·6]) than in the fasting (5·9% [0·5]; <0·0001) or 2 h (5·9% [0·6]; <0·0001) sugroups. Additionally, the fasting and 2 h subgroup had a higher proportion of individuals with moderate or high risk of cardiovascular disease than did the fasting subgroup (p=0·02). A classic pattern of β-cell decompensation before diagnosis was noted only in the fasting and 2 h subgroup. Additionally, glucose concentrations and insulin resistance accelerated more substantially before diagnosis in the fasting and 2 h subgroup than in the fasting subgroup or the 2 h subgroup. INTERPRETATION Patients with type 2 diabetes diagnosed on the basis of increased fasting glucose concentrations or 2 h glucose concentrations, or both, have distinct cardiometabolic risk development before diagnosis. FUNDING UK Medical Research Council, UK Economic and Social Research Council, British Heart Foundation, UK Health and Safety Executive, UK Department of Health, US National Heart Lung and Blood Institute, US National Institute on Aging, US Agency for Health Care Policy Research, and John D and Catherine T MacArthur Foundation.
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Affiliation(s)
| | - Daniel R Witte
- Steno Diabetes Center, Gentofte, Denmark; Centre de Recherche Public de la Santé, Strassen, Luxembourg
| | - Adam G Tabák
- Department of Epidemiology and Public Health, University College London, London, UK; First Department of Medicine, Semmelweis University, Budapest, Hungary
| | | | - Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Eric J Brunner
- Department of Epidemiology and Public Health, University College London, London, UK
| | - Mika Kivimäki
- Department of Epidemiology and Public Health, University College London, London, UK
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Bongaerts BWC, Rathmann W, Heier M, Kowall B, Herder C, Stöckl D, Meisinger C, Ziegler D. Older subjects with diabetes and prediabetes are frequently unaware of having distal sensorimotor polyneuropathy: the KORA F4 study. Diabetes Care 2013; 36:1141-6. [PMID: 23275355 PMCID: PMC3631873 DOI: 10.2337/dc12-0744] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Distal sensorimotor polyneuropathy (DSPN) is a severe complication of type 2 diabetes. This study aimed to assess the prevalence of unawareness of DSPN in prediabetes and diabetes in a sample of the older population of Augsburg, Germany. RESEARCH DESIGN AND METHODS Glucose tolerance status was determined in 61- to 82-year-old participants of the population-based KORA F4 Study (2006-2008) (n = 1,100). Clinical DSPN was defined as the presence of bilaterally impaired foot-vibration perception and/or bilaterally impaired foot-pressure sensation. DSPN case subjects were considered unaware of their condition when answering "no" to the question, "Has a physician ever told you that you are suffering from nerve damage, neuropathy, polyneuropathy, or diabetic foot?" RESULTS Clinical DSPN was prevalent in 154 (14%) participants, 140 of whom were unaware of their disorder. At a prevalence of 23.9% (95% CI 12.6-38.8), participants with combined impaired fasting glucose and impaired glucose tolerance had the highest prevalence of DSPN. Of these, 10 of 11 (91%) were unaware of having clinical DSPN. Participants with known diabetes had an equally high prevalence of DSPN [22.0% (16.2-28.9)], with 30 of the 39 (77%) DSPN case subjects unaware of having the disorder. Among subjects with known diabetes who reported to have had their feet examined by a physician, 18 of 25 (72%) clinical DSPN case subjects emerged unaware of having DSPN. CONCLUSIONS Our findings showed a high prevalence of unawareness of having clinical DSPN among the prediabetic and diabetic groups and an insufficient frequency of professional foot examinations, suggesting inadequate attention to diabetic foot prevention practice.
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Affiliation(s)
- Brenda W C Bongaerts
- Leibniz Center for Diabetes Research, Heinrich Heine University Dusseldorf, Dusseldorf, Germany
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Lu B, Hu J, Wen J, Zhang Z, Zhou L, Li Y, Hu R. Determination of peripheral neuropathy prevalence and associated factors in Chinese subjects with diabetes and pre-diabetes - ShangHai Diabetic neuRopathy Epidemiology and Molecular Genetics Study (SH-DREAMS). PLoS One 2013; 8:e61053. [PMID: 23613782 PMCID: PMC3628856 DOI: 10.1371/journal.pone.0061053] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2013] [Accepted: 03/05/2013] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE This study determined the prevalence and factors associated with peripheral neuropathy (PN) in subjects with diabetes mellitus, impaired glucose regulation (IGR), and normal glucose tolerance (NGT) in a community-based Chinese population. RESEARCH DESIGN AND METHODS A total of 2035 subjects in Shanghai were classified as having NGT, IGR, or diabetes. All subjects underwent complete foot examination. PN was assessed according to the neuropathy symptom and neuropathy disability scores. Binary logistic regression was performed to analyze the contributions of factors to PN. RESULTS The prevalence of PN was 8.4%, 2.8%, and 1.5% in diabetes mellitus, IGR, and NGT subjects, respectively (P<0.05 for diabetes vs. NGT, and IGR). The subjects with known diabetes had the highest frequency of PN (13.1%). Among the subjects without diabetes, those with PN were older, had a higher waist circumference and 2-h postprandial plasma glucose levels, and were more likely to be hypertensive. Among the IGR subjects, other than age, the 2-h postprandial plasma glucose level was an independent factor significantly associated with PN. Meanwhile, among the subjects with diabetes, PN was associated with fasting plasma glucose, duration of diabetes, and decreased estimated glomerular filtration rate. CONCLUSIONS The prevalence of PN is slightly higher in individuals with IGR than that in individuals with NGT, but small fibre damage in IGR as the earliest nerve fibre deficit may be underestimated in our study. As an independent risk factor, postprandial plasma glucose level may be an important target for strategies to prevent or improve PN in IGR subjects.
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Affiliation(s)
- Bin Lu
- Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai, China
| | - Ji Hu
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Jiangsu, China
| | - Jian Wen
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Jiangsu, China
| | - Zhaoyun Zhang
- Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai, China
| | - Linuo Zhou
- Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai, China
| | - Yiming Li
- Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai, China
- Department of Endocrinology, Jing’An District Centre Hospital of Shanghai, Shanghai, China
| | - Renming Hu
- Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai, China
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Papanas N, Ziegler D. Polyneuropathy in Impaired Glucose Tolerance: Is Postprandial Hyperglycemia the Main Culprit? A Mini-Review. Gerontology 2013. [DOI: 10.1159/000343988] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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