This doctoral thesis was written in the doctoral school called the Network of Academic Health Centres (AcaHC) of the Department of General Practice and Primary Health Care, Faculty of Medicine, in University of Helsinki. The atmosphere of AcaHC has been friendly and supportive – the researchers have gradually become friends. Without these colleagues, this thesis would never have become ready. The multiprofessional idea of the group has been a great richness. Professors Mats Brommels and Johan Eriksson earn to be mentioned separately: it has been a great pleasure for me to notice that persons with the most wisdom can be so easily contacted.
I wish to express my deepest gratitude to my supervisors:
Docent Outi Elonheimo, the coordinator of AcaHC, for her great support throughout the whole decade with this work. Outi or “Tintti” has met a vast challenge when trying to make academic workers of health centres to researchers and doctors. The monthly seminars of AcaHC usually began with a cavalcade of reasons why so little progress had “just now” been achieved.
Professor h.c. Timo Sane with his overwhelming knowledge and experience with endocrinology and diabetes care has made it possible for me to complete this thesis. My career as a diabetologist began when I was working as an assistant doctor in Meilahti hospital department 111 during two consecutive summers about 25 years ago. I had the honour to work with professor Sane and the present archiatre Risto Pelkonen - both exceptional gentlemen with a lot of knowledge combined with an appreciating attitude to their patients. Those months taught me much about medicine and humanity.
I want to thank the official reviewers, docents Liisa Hiltunen and Jorma Lahtela, for their constructive evaluation of this thesis. Their comments helped me to make the manuscript to its final mode. Their concentration to the review and the amount of time given to the work made me a great influence.
This study would not have been possible without the work of the nurses in Kouvola and Nurmijärvi who helped me to reach the diabetic population of these municipalities. I want to extend my sincerest thanks to all of them. Especially I want to mention the already retired diabetes specialist nurse of Kouvola, Mrs Anja Borgman. During the work, I could notice how appreciated she was among the diabetic patients of Kouvola.
Naturally I am grateful to my employer for the possibility to make this thesis and for the possibility to develop my own work. I have been lucky with having co-workers, who are motivated to do their work well and to search for better outcomes.
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The past ten years have demanded a lot of my family; most of the work was done during the free time. I am grateful to my wife, Marita, for her understanding patience and support. I have had the privilege to have such a fine family and a home where it is always easy and relaxing to be.
The study behind this thesis was financially granted by the foundation of Kyllikki and Uolevi Lehikoinen, the Avohoidon tutkimussäätiö and the Diabetes Research Foundation. I want to thank these foundations for their support, which was especially important during the early phases of the study when the study population was gathered.
There are still many other people who have been important for this study project and I have no possibility to mention them all in this text. Many thanks for all of you.
I devote this thesis to the memory of my brother Jukka, who got cerebral cancer shortly after his academic dissertation and died after nine heavy months. His death caused the longest break in my academic work and it made me understand, how tiny the meaning of one person or one thesis can be in the history and in the universe.
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9 References
1. International Diabetes Federation (2011) Diabetes Atlas 5th Edition, Brussels
2. Chatterton H, Younger T, Fischer A, Khunti K: Risk identification and intervention to prevent type 2 diabetes in adults at high risk: Summary of NICE guidance. BMJ 2012;345:4624
3. Santaguida PL, Balion C, Hunt D, Morrison K, Gerstein H, Raina P, Booker L, Yazdi H.
Diagnosis, prognosis, and treatment of impaired glucose tolerance and impaired fasting glucose. [Review] [85 refs] Evidence Report: Technology Assessment (Summary). 2005;128:1-11
4. Harjutsalo V, Sund R, Knip M, Groop PH: Incidence of type 1 diabetes in Finland. JAMA 2013;310(4):427-428
5. Harjutsalo V, Sjöberg L, Tuomilehto J: Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study. Lancet 2008;371(9626):1777-1782
6. Hussen HI, Yang D, Cnattingius S, Moradi T. Type I diabetes among children and young adults:
the role of country of birth, socioeconomic position and sex. Pediatric Diabetes 2013;14:138-148
7. Oikarinen M, Tauriainen S, Oikarinen S, Honkanen T, Collin P, Rantala I, Mäki M, Kaukinen K, Hyöty H. Type 1 diabetes is associated with enterovirus infection in gut mucosa. Diabetes 2012;61:687-691
8. Virtanen SM, Nevalainen J, Kronberg-Kippila C, Ahonen S, Tapanainen H, Uusitalo L, Takkinen HM, Niinisto S, Ovaskainen ML, Kenward MG, Veijola R, Ilonen J, Simell O, Knip M. Food consumption and advanced beta cell autoimmunity in young children with HLA-conferred susceptibility to type 1 diabetes: a nested case-control design. Am J Clin Nutr 2012;95:471-478
9. van Belle TL, Coppieters KT, von Herrath MT. Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol Rev 2011; 91(1):79-118
10. Canivell S, Gomis R. Diagnosis and classification of autoimmune diabetes mellitus.
Autoimmun Rev 2014;13:403-407
11. Santin I, Eizirik DL. Candidate genes for type 1 diabetes modulate pancreatic islet inflammation and beta-cell apoptosis. Diabetes Obes Metab 2013;15:71-81
68
12. Kallionpää H, Laajala E, Oling V, Harkonen T, Tillmann V, Dorshakova NV, Ilonen J, Lahdesmaki H, Knip M, Lahesmaa R.; DIABIMMUNE Study Group. Standard of hygiene and immune adaptation in newborn infants. Clin Immunol 2014;155:136-147
13. Laitinen OH, Honkanen H, Pakkanen O, Oikarinen S, Hankaniemi MM, Huhtala H, Ruokoranta T, Lecouturier V, Andre P, Harju R, Virtanen SM, Lehtonen J, Almond JW, Simell T, Simell O, Ilonen J, Veijola R, Knip M, Hyoty H. Coxsackievirus B1 is associated with induction of beta-cell autoimmunity that portends type 1 diabetes. Diabetes 2014; 63:446-455
14. Diabetes current care summary 12.09.2013
http://www.kaypahoito.fi/web/kh/suositukset/naytaartikkeli/tunnus/ccs00032
15. Forssas E, Sund R, Manderbacka K, Arffman R, Ilanne-Parikka P, Keskimäki I. Diabeetikoilla yhä suuri ylikuolleisuus muuhun väestöön verrattuna. Suom Laakaril 2010;26:2359-2367 16. Valle T, Koivisto V, Reunanen A, Kangas T, Rissanen A: Glycemic control in patients with
diabetes in Finland. Diabetes Care 1999;22:575–579
17. Valle T, Tuomilehto J. Diabeetikkojen hoitotasapaino Suomessa vuosina 2000-2001. DEHKO-raportti 2004:1
18. Valle T. The balance of care of diabetic patients in Finland in 2009 – 2010: the Finnish diabetes association.
DEHKO;2010:5.http://www.diabetes.fi/files/1488/DEHKOraportti_2010_5_Diabeetikkojen_h oitotasapaino_Suomessa_vuosina_2009-2010.pdf
19. Action to Control Cardiovascular Risk in Diabetes Study Group. Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. New England Journal of Medicine 2008;358:2545-2559
20. Bonds DE, Kurashige EM, Bergenstal R, Brillon D, Domanski M, Felicetta JV, Fonseca VA, Hall K, Hramiak I, Miller ME, Osei K, Simons-Morton DG. ACCORD Study Group. Severe hypoglycaemia monitoring and risk management procedures in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol 2007; 99:80-89
21. Liu L, Li X, Xiang Y, Huang G, Lin J, Yang L, Zhao Y, Yang Z, Hou C, Li Y, Liu I, Zhu D, Leslie D, Wang X, Zhou Z, on behalf of the LADA China Study Group. Latent Autoimmune Diabetes in Adults With Low-Titer GAD Antibodies: Similar Disease Progression With Type 2 Diabetes: A
69
Nationwide, Multicenter Prospective Study (LADA China Study 3) Diabetes Care published ahead of print October 21, 2014, doi:10.2337/dc14-1770
22. Laakso M. Tyypin 2 diabetes ja geenitutkimuksen vallankumous. Diabetes ja lääkäri 2012;41:16-18
23. Schafer SA, Machicao F, Fritsche A, Haring HU, Kantartzis K. New type 2 diabetes risk genes provide new insights in insulin secretion mechanisms. Diabetes research and clinical practice 2011;93Suppl.1:9-24
24. Miettinen PJ, Tuomi TM. MODY-diabetes – yksigeeninen haiman beetasolujen kehitys- ja toimintahäiriö. Lääketieteellinen Aikakauskirja Duodecim 2012;218:1989-1998
25. Fajans SS, Bell GI, Polonsky KS. Mechanisms of disease: Molecular mechanisms and clinical pathophysiology of Maturity-Onset Diabetes of the Young (Review). NEJM 2001;345:971-980
26. Liu H, Zhang C, Zhang S, Wang L, Leng J, Liu D, Fang H, Li W, Yu Z, Yang X, Dong L, Hu G.
Prepregnancy body mass index and weight change on postpartum diabetes risk among gestational diabetes women. Obesity 2014;22:1560-1567
27. Buchanan TA, Kjos SL. Gestational diabetes: risk or myth? [Review] J Clin Endocrin Metab 1999;84:1854-1857
28. Ong KL, Barter PJ, Waters DD. Cardiovascular drugs that increase the risk of new-onset diabetes (Review). Am Heart J 2014;167:421-428
29. Peltonen M, Korpi-Hyövälti E, Oksa H, Puolijoki H, Saltevo J, Vanhala M, Saaristo T, Saarikoski L, Sundvall J, Tuomilehto J. Prevalence of obesity, type 2 diabetes, and other disturbances in glucose metabolism in Finland – the FIN-D2D survey. Finnish Medical Journal 2006;61:163-170. English Summary
30. Kangas T: Health Care of People with Diabetes in Finland: Inpatient and Outpatient Care, Metabolic and Direct Costs of Care. PhD thesis. STAKES; 1995. Research reports 58
31. Ho M, Marger M, Beart J,Yip I, Shekelle P. Is the quality of diabetes care better in a diabetes clinic or in a general medicine clinic? Diabetes Care 1997;20:472-475
32. Arts EE, Landewe-Cleuren SA, Schaper NC, Vrijhoef HJ. The cost-effectiveness of substituting physicians with diabetes nurse specialists: a randomized controlled trial with 2-year follow-up. J Adv Nurs 2012;68:1224-1234
70
33. Ovhed I, Johansson E, Odeberg H, Rastam L. A comparison of two different team models for treatment of diabetes mellitus in primary care. Scand J Caring Sci 2000;14:253-258
34. Gibson OR, Segal L, McDermott RA. A systematic review of evidence on the association between hospitalisation for chronic disease related ambulatory care sensitive conditions and primary health care resourcing. BMC Health Services Research, 2013;13:336
35. SavinettiRose B, Bolmer L. Understanding continuous subcutaneous insulin infusion therapy.
AJN 1997;97:42-48
36. Scheiner G, Sobel R, Smith D, Pick A, Kruger D. King J, Green K. Insulin pump therapy:
guidelines for successful outcomes. Diabetes Educ 2009;32:Suppl 2:29S-41S
37. United Kingdom Prospective Diabetes Study (UKPDS). 13: Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years. BMJ 1995;310:83-88
38. Huang W, Castelino RL, Peterson GM. Metformin usage in type 2 diabetes mellitus: are safety guidelines adhered to? Intern Med J 2014;44:264-272
39. Griffin SJ, Borch-Johnsen K, Davies MJ, Khunti K, Rutten GE, Sandbaek A, Sharp SJ, Simmons RK, van den Donk M, Wareham NJ, Lauritzen T. Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial. Lancet, 2011;378:156-167
40. Webb DR, Khunti K, Gray LJ, Srinivasan BT, Farooqi A, Wareham N, Griffin SC, Davies MJ.
ADDITION-Leicester study,group. Intensive multifactorial intervention improves modelled coronary heart disease risk in screen-detected Type 2 diabetes mellitus: a cluster randomized controlled trial. Diabet.Med.2012;29: 531-540
41. Gregg EW, Li Y, Wang J, Burrows NR, Ali MK, Rolka D, Williams DE, Geiss L. Changes in diabetes-related complications in the United States, 1990–2010. NEJM 2014;370:1514-1523 42. Ikonen TS, Sund R, Venermo M, Winell K. Fewer major amputations among individuals with
diabetes in Finland in 1997-2007: a population-based study. Diabetes Care 2010;33:2598-2603
43. Cryer PE. Hypoglycemia in Diabetes, in Textbook of Diabetes 2010, Fourth Edition (eds RIG Holt, CS Cockram, A Flyvbjerg and BJ Goldstein), Wiley-Blackwell, Oxford, UK
71
44. ADA. Defining and reporting hypoglycemia in diabetes. Diabetes Care 2005;28(5):1245-1249 45. Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose
lowering in type 2 diabetes. NEJM 2008;358:2545–2559
46. Rydén L, Standl E, Bartnik M, Van den Berghe G, Betteridge J, de Boer MJ, Cosentino F, Jonsson B, Laakso M, Malmberg K, Priori S, Ostergren J, Tuomilehto J, Thrainsdottir I, Vanhorebeek I, Stramba-Badiale M, Lindgren P, Qiao Q, Priori SG, Blanc JJ, Budaj A, Camm J, Dean V, Deckers , Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo J, Zamorano JL, Deckers JW, Bertrand M, Charbonnel B, Erdmann E, Ferrannini E, Flyvbjerg A, Gohlke H, Juanatey JR, Graham I, Monteiro PF, Parhofer K, Pyorala K, Raz I, Schernthaner G, Volpe M, Wood D. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J 2007;28:88-136 Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA 2002; 287:2563-2569
47. Tolonen N, Hietala K, Forsblom C, Harjutsalo V, Makinen VP, Kyto J, Summanen PA, Thorn LM, Waden J, Gordin D, Taskinen MR. The FinnDiane Study Group. Associations and interactions between lipid profiles, retinopathy and nephropathy in patients with type 1 diabetes: the FinnDiane Study. J Intern Med 2013;274:469-479
48. Henricsson M, Nilsson A, Groop L, Heijl A, Janzon L. Prevalence of diabetic retinopathy in relation to age at onset of the diabetes, treatment, duration and glycemic control. Acta Ophthalmol Scand 1996;74:523-527
49. Diabeettinen retinopatia Käypä hoito -suositus 15.12.2014
http://www.kaypahoito.fi/web/kh/suositukset/suositus?id=hoi50043 50. Raskausdiabetes Käypä hoito -suositus 26.06.2013
http://www.kaypahoito.fi/web/kh/suositukset/suositus?id=hoi50068 51. Diabeettinen nefropatia Käypä hoito –suositus 22.08.2007
http://www.kaypahoito.fi/web/kh/suositukset/suositus?id=hoi50060
72
52. Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR. Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int 2003;63:225-232
53. Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR. Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes 2006;55:1832-1839
54. Scheen AJ, Paquot N, Lefebvre PJ [United Kingdom Prospective Diabetes Study (UKPDS): 10 years later] Rev Med Liege 2008; 63:624-629
55. White NH, Sun W, Cleary PA,Tamborlane WV, Danis RP, Hainsworth DP, Davis MD. DCCT-EDIC Research Group. Effect of prior intensive therapy in type 1 diabetes on 10-year progression of retinopathy in the DCCT/EDIC: comparison of adults and adolescents. Diabetes 2010;59:1244-1253
56. Statistics Finland. http://tilastokeskus.fi/til/ksyyt/index.html 30.12.2014
57. Bus SA, Maas M, de Lange A, Michels RP, Levi M. Elevated plantar pressures in neuropathic diabetic patients with claw/hammer toe deformity. J Biomech 2005;38:1918-1925
58. Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Lancet 2005;366:1719-1724
59. Maletkovic J, Drexler A. Diabetic ketoacidosis and hyperglycemic hyperosmolar state.
Endocrinol Metab Clin North Am 2013;42:677-695
60. Kati Taskinen. Kuolemansyyt.tilasto@stat.fi. Written notice. Statistics Finland 27.01.2014.
http://www.stat.fi/index.html
61. Van Ness-Otunnu R, Hack JB. Hyperglycemic crisis. [Review]. J Emerg Med 2013;45:797-805 62. Clarke W, Cox DJ, Gonder-Frederick LA, Julian D, Schlundt D, Polonsky W. Reduced awareness
of hypoglycemia in adults with IDDM: A prospective study of hypoglycemic frequency and associated symptoms. Diabetes Care 1995;18:517–522
63. Mäkimattila S. Kuka pelkää hypoglykemiaa? Hypoglykemia diabeteksen hoidon haasteena.
Yleislääkäri 2013;5:9-12
64. Amiel SA, Dixon T, Mann R, Jameson K. Hypoglycaemia in type 2 diabetes. Diabet Med 2008;25:245–254
73
65. Pedersen-Bjergaard U, Pramming S, Heller SR, Wallace TM, Rasmussen AK, Jorgensen HV, et al. Severe hypoglycaemia in 1076 adult patients with type I diabetes: Influence of risk markers and selection. Diabetes Metab Res Rev 2004;20:479–486
66. Gürlec A, Erbas T, Gedik O. Frequency of severe hypoglycaemia in type 1 and type 2 diabetes during conventional insulin therapy. Exp Clin Endocrinol Diabetes 1999;107:220-224
67. UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia 2007;50:1140-1147
68. ter Braak EW, Appelman AM, van de Laak M, Stolk RP, van Haeften TW, Erkelens DW. Clinical characteristics of type 1 diabetic patients with and without severe hypoglycemia. Diabetes Care 2000;23:1467–1471
69. The Diabetes Control and Complications Trial Research Group. Hypoglycaemia in the Diabetes Control and Complications Trial. Diabetes 1997;46:271-286
70. Battelino T, Conget I, Olsen B, Schutz-Fuhrmann J, Hommel E, Hoogma R, Schierloch U, Sulli N, Bolinder J. SWITCH Study Group. The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial.
Diabetologia 2012;55:3155-3162
71. Pickup JC. Management of diabetes mellitus: is the pump mightier than the pen? Nature Reviews Endocrinology 2012;8:425-433
72. Olsovsky J, Beranek M. [The influence of long-term therapy with the insulin pump (CSII) in patients with type 1 diabetes mellitus on metabolic compensation and on the incidence of hypoglycaemia. Comparison with intensified conventional insulin therapy (MDI)]
VnitrniLekarstvi 2007;53:637-645
73. Garg S, Brazg RL, Bailey TS, Buckingham BA, Slover RH, Klonoff DC, Shin J, Welsh JB, Kaufman FR. Reduction in duration of hypoglycaemia by automatic suspension of insulin delivery: the in-clinic ASPIRE study. Diabetes Technology & Therapeutics 2012;14:205-209
74. Bergenstal RM, Klonoff DC, Garg SK, Bode BW, Meredith M, Slover RH, Ahmann AJ, Welsh JB, Lee SW, Kaufman FR. ASPIRE In-Home Study Group. Threshold-based insulin-pump interruption for reduction of hypoglycaemia. NEJM 2013;369: 224-232
74
75. Akram K, Pedersen-Bjergaard U, Borch-Johnsen K, Thorsteinsson B. Frequency and risk factors of severe hypoglycaemia in insulin-treated type 2 diabetes: a literature survey. J Diabetes Complications 2006;20:402-408
76. Cryer PE. Death during intensive glycemic therapy of diabetes: mechanisms and implications.
The American Journal of Medicine 2011;124:993-996
77. Whitmer RA, Karter AJ, Yaffe K, Quesenberry Jr CP, Selby JV. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 2008;301::1565-1572 78. Languren G, Montiel T, Julio-Amilpas A, Massieu L. Neuronal damage and cognitive
impairment associated with hypoglycaemia: An integrated view. Neurochem Int 2013;63:331-343
79. Cryer PE. The barrier of hypoglycaemia in diabetes. Diabetes 2008;57:3169–3176
80. Davis S, Alonso MD. Hypoglycemia as a barrier to glycemic control. J Diabet Complications 2004;18:60–68
81. Fidler C, Elmelund Christensen T, Gillard S. Hypoglycaemia: an overview of fear of hypoglycaemia, quality of life and impact on costs. J Med Econ 2011;14:646-655
82. Wild D, von Maltzahn R, Brohan E, Clauson P, Gonder-Frederick L. A critical review of the literature on fear of hypoglycemia in diabetes: Implications for diabetes management and patient education. Patient Educ.Couns. 2007;68:10-15
83. Leese GP, Wang J, Broomhall J, Kelly P, Marsden A, Morrison W et al. Frequency of severe hypoglycemia requiring emergency treatment in type 1 and type 2 diabetes: a population-based study of health service resource use. Diabetes Care 2003;26:1176–1180
84. Brod M, Christensen T, Thomsen TL, Bushnell DM. The impact of non-severe hypoglycemic events on work productivity and diabetes management. Value in Health 2011;14:665-671 85. Jonsson L, Bolinder B, Lundkvist J. Cost of hypoglycemia in patients with Type 2 diabetes in
Sweden. Value in Health 2006;9:193-198
86. Mattila EM, Kuisma MJ, Sund KP, Voipio-Pulkki LM. Out-of-hospital hypoglycaemia is safely and cost-effectively treated by paramedics. Eur J Emergency Med 2004;11:70–74
75
87. Haukka J, Hoti F, Erästö P, Saukkonen T, Mäkimattila S. Evaluation of the incidence and risk of hypoglycemic coma associated with selection of basal insulin in the treatment of diab: a Finnish register linkage study. Pharmacoepidemiology and Drug Safety 2013;22:1326-1335 88. Standards of medical care in diabetes-2014. American Diabetes Association. Diabetes Care
2014;37Suppl.1:14-80
89. Schernthaner G. Diabetes and Cardiovascular Disease: Is intensive glucose control beneficial or deadly? Lessons from ACCORD, ADVANCE, VADT, UKPDS, PROactive, and NICE-SUGAR.
Wiener Medizinische Wochenschrift 2010;160:8-19
90. Hirakawa Y, Arima H, Zoungas S, Ninomiya T, Cooper M, Hamet T, Mancia G, Poulter N, Harrap S, Woodward M, Chalmers J. Impact of visit-to-visit glycemic variability on the risk of macrovascular and microvascular events and all-cause mortality in type 2 diabetes: the ADVANCE trial. Diabetes Care 2014;37:2359-2365
91. Cox D, Clarke W, Gonder-Frederick L, Kovatchev B. Driving mishaps and hypoglycaemia: risk and prevention. Int J Clin Pract 2001;123(suppl):38–42
92. Cox DJ, Kovatchev B, Vandecar K, Gonder-Frederick L, Ritterband L, Clarke W. Hypoglycemia preceding fatal car collisions. Diabetes Care. 2006;29:467–468
93. Cox DJ, Ford D, Gonder-Frederick L, Clarke W, Mazze R, Weinger K, Ritterband L. Driving mishaps among individuals with type 1 diabetes: a prospective study. Diabetes Care 2009;32:2172–2180
94. Cox DJ, Gonder-Frederick LA, Kovatchev BP, Julian DM, Clarke WL. Progressive hypoglycaemia’s impact on driving simulation performance. Occurrence, awareness and correction. Diabetes Care 2000;23:163–170
95. Inkster B, Frier BM. Diabetes and driving. Diabetes, Obesity and Metabolism 2013;15:775-783
96. Clarke WL, Cox DJ, Gonder-Frederick LA, Kovatchev B. Hypoglycaemia and the decision to drive a motor vehicle by persons with diabetes. JAMA1999;282:750–75
97. Sosiaali- ja terveysministeriön asetus ajoterveydestä 25.11.2011/386
http://www.stm.fi/c/document_library/get_file?folderId=40880&name=DLFE-16936.pdf
76
98. Stork A. Hypoglycaemia unawareness: judge driving ability prudently. Nederlands Tijdschrift voor Geneeskunde 2011;155:A4144
99. Pedersen-Bjergaard U, Faerch L, Allingbjerg ML, Agesen R, Thorsteinsson B. The influence of new European Union driver's license legislation on reporting of severe hypoglycemia by patients with type 1 diabetes. Diabetes Care 2015;38:29-33
100. Kangas T, Aro S, Koivisto VT, Salinto M, Laakso M, Reunanen A. Structure and costs of health care of diabetic patients in Finland. Diabetes Care 1996;19:494-497
101. Koski S. Diabetesbarometri 2010 25.01.2015
http://www.diabetes.fi/files/1377/Diabetesbarometri_2010.pdf
102. Zhang P, Zhang X, Brown J, Vistisen D, Sicree R, Shaw J, Nichols G. Global healthcare expenditure on diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010;87:293-301
103. Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol 1995;75:894-903
104. Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complication Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA 2002;287:2563-2569
105. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Turner RC, Holman RR.
Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405-412
Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405-412