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Article Number - 974E7B515872


Vol.4(4), pp. 46-57 , September 2013
DOI: 10.5897/JPAP2013.0001
ISSN: 2141-260X



Review

The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus


Ozougwu, J. C.1*, Obimba, K. C.2, Belonwu, C. D.3, and Unakalamba, C. B.4




1Physiology and Biomedical Research Unit, Department of Biological Sciences, College of Basic and Applied Sciences, Rhema University Aba, Abia StateNigeria.

2Department of Biochemistry, School of Science, Federal University of Technology Owerri, Imo State. Nigeria.

3Department of Biochemistry, Faculty of Chemical Sciences, University of Portharcourt, Rivers State. Nigeria.

4Department of Zoology and Environmental Biology, University of Nigeria, Nsukka, Enugu state, Nigeria.


Email: jevaschubby@yahoo.com






 Accepted: 17 June 2013  Published: 30 September 2013

Copyright © 2013 Author(s) retain the copyright of this article.
This article is published under the terms of the Creative Commons Attribution License 4.0


The aim of this paper is to review the information on type 1 and type 2 diabetes with emphasis on its etiology, pathogenesis and pathophysiology via literature review. Diabetes is a group of metabolic disorders characterized by a chronic hyperglycemic condition resulting from defects in insulin secretion, insulin action or both. Type 1 diabetes is the result of an autoimmune reaction to proteins of the islets cells of the pancreas while type 2 diabetes is caused by a combination of genetic factors related to impaired insulin secretion, insulin resistance and environmental factors such as obesity, overeating, lack of exercise and stress, as well as aging. The pathogenesis of selective β-cell destruction within the islet in type 1 diabetes mellitus is difficult to follow due to marked heterogeneity of the pancreatic lesions. At the onset of overt hyperglycemia, a mixture of pseudoatrophic islets with cells producing glycogen, somatostatin and pancreatic polypeptide, normal islets and islets containing both β-cells and infiltrating lymphocytes and monocytes may be seen. The autoimmune destruction of pancreatic β cells leads to a deficiency of insulin secretion that leads to the metabolic derangements associated with type 1 diabetes. The main pathophysiological features of type 2 diabetes are impaired insulin secretion and increased insulin resistance. The impairment of pancreatic β cell function notably shows progression overtime in type 2 diabetes although aging, obesity, insufficient energy consumption, alcohol drinking, smoking, etc are independent risk factors of pathogenesis of type 2 diabetes mellitus.   

 

Key words: Diabetes Mellitus, Pathophysiology, Pathogenesis, Etiology.

Akinmokun A, Harris P, Home PD, Alberti KG (1992). Is diabetes always diabetes? Diabetes Res. Clin. Pract. 18:131-136.
http://dx.doi.org/10.1016/0168-8227(92)90009-G
 
Al Homsi MF, Lukic ML (1992). An Update on the pathogenesis of Diabetes Mellitus, Department of Pathology and Medical Microbiology (Immunology Unit)Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
PMid:1421445
 
American Diabetes Association (2001). Diabetes 2001 Vital statistics. Alexandra, VA: ADA.
PMid:11522665
 
Bennett N, Dodd T, Flatley J, Freeth S, Boiling K (1995). Health survey for England 1993, London; HMSO.
 
Blood A, Hayes TM, Gamble DR (1975). Register of newly diagnosed diabetic children. BMJ. 3:580-583.
http://dx.doi.org/10.1136/bmj.3.5983.580
 
Bjorntorp P (1992). Abdominal fat distribution and disease: an overview of epidemiological data. Annals Med. 24(1):15-18.
http://dx.doi.org/10.3109/07853899209164140
PMid:1575956
 
Bonadonna RC, Saccomani MP, Seely L, et al. (1993). Glucose transport in human skeletal muscle: the in vivo response to insulin. Diabetes. 42:191-198.
http://dx.doi.org/10.2337/diabetes.42.1.191
http://dx.doi.org/10.2337/diab.42.1.191
PMid:8093605
 
Campbell IT, Kay TWH, Oxbrow L, Harrison TC (1991). Essential role for Interferon Gama and interleukin 6 in autoimmune, insulin-dependent diabetes in NOD/Wehi mice. J. Clin. Invest. 87:739-742.
http://dx.doi.org/10.1172/JCI115055
PMid:1899431 PMCid:PMC296368
 
Comi RJ, Grunberger G, Gorden P (1987). Relationship of insulin binding and Insulin-stimulated tyrosine kinase activity is altered in type II diabetes. J. Clin. Invest. 79:453-62.
http://dx.doi.org/10.1172/JCI112833
PMid:3543053 PMCid:PMC424100
 
Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon KH, Hu FB (2009). Diabetes in Asia; epidemiology, risk factors, and pathophysiology. JAMA, 301:2129-2140.
http://dx.doi.org/10.1001/jama.2009.726
PMid:19470990
 
Colagiuri S (2010). Diabesity; Therapeutic Options. Diabetes Obes. Metab. 12:463-473.
http://dx.doi.org/10.1111/j.1463-1326.2009.01182.x
PMid:20518802
 
Cook JT, Hattersley AT, Levy JC, Patel P, Wainscoat JS, Hockaday TD, Turner RC (1993). Distribution of Type II diabetes in nuclear families. Diabetes. 42:106-12.
http://dx.doi.org/10.2337/diabetes.42.1.106
http://dx.doi.org/10.2337/diab.42.1.106
PMid:8420807
 
Defronzo RA, Ferrannini E (1988). Lily Lecture 1987. The Triumvirate: Beta Cell, Muscle, Liver. A Collusion Responsible for NIDDM. Diabetes. 37:667-687.
http://dx.doi.org/10.2337/diab.37.6.667
PMid:3289989
 
Enoki S, Mitsukawa T, Takemura J, Nakazato M, Aburaya J, Toshimori H, Matsukara S (1992). Plasma islet amyloid polypeptide levels in obesity, impaired glucose tolerance and non-insulin-dependent diabetes mellitus. Diabetes Res. Clin. Pract. 15(l):97-102.
http://dx.doi.org/10.1016/0168-8227(92)90074-2
 
EURODIAB ACE Study Group (2000). Variation and trends in incidence of childhood diabetes in Europe, Lancet. 335:873-876.
 
Evephart JE, Pettit DJ, Bennett PH, Knowler WC (1992). Duration of obesity increases the incidence of NIDDM. Diabetes. 41:235-240.
http://dx.doi.org/10.2337/diabetes.41.2.235
http://dx.doi.org/10.2337/diab.41.2.235
 
Felber JP (1992). From obesity to diabetes: pathophysiological considerations. Int. J. Obes. 1992; 16:937-952.
 
Fowell D, Mcknight AI, Powrie F, Dyke R, Mason D (1991). Subsets of CD4+ T cells and their roles in the induction and prevention of autoimmunity. Immunol. Rev. 123:37-64.
http://dx.doi.org/10.1111/j.1600-065X.1991.tb00605.x
PMid:1684782
 
Froguel P, Zouali H, Vionnet N, Velho G, Vaxillaire M, Sun F, Lesage S, Stoffel M, Takeda J, Passa P,Permutt MA,Beckmann JS, Bell GI, Cohen D (1993). Familial hyperglycemia due to mutations in glucokinase definition of a subtype of diabetes mellitus. N Engl J Med. 328(10):697-702.
http://dx.doi.org/10.1056/NEJM199303113281005
PMid:8433729
 
Gabbay K H (1980). The Insulinopathies. N. Engl. J. Med. 302:165-7.
http://dx.doi.org/10.1056/NEJM198001173020308
PMid:7350441
 
González EL, Johansson S, Wallander MA, Rodríguez LA (2009). Trends in the prevalence and incidence of diabetes in the UK: 1996 – 2005. J. Epidemiol. Community Health. 63: 332-336.
http://dx.doi.org/10.1136/jech.2008.080382
PMid:19240084
 
Gill RG, Haskins K (1993). Molecular mechanisms underlying diabetes and other autoimmune diseases. Immunol. Today. M:49-51.
 
Guyton AC, Hall JE (2006). Textbook of Medical physiology. 11th Edition. Elsevier Inc, New Delhi.
PMCid:PMC1860893
 
Haffner SM, Mitchell BD, Stern MP, Hazuda HP, Patterson JK (1992). Public health significance of upper body adiposity for non-insulin dependent diabetes in Mexican Americans. Int. J. Obes. 16(3):177-184.
 
Hattersley AT, Turner RC, Permutt MA, Patel P, Tanizawa Y, Chiu KC, O'Rahilly S, Watkins P, Wainscoat JS (1992). Linkage of type 2 diabetes to the glucokinase gene. Lancet. 339:1307-1310.
http://dx.doi.org/10.1016/0140-6736(92)91958-B
 
Holt G. I. (2004). Diagnosis, epidemiology and pathogenesis of diabetes mellitus an update for Psychiatrists. Br. J. Psychiatry. 184:s55- s63.
http://dx.doi.org/10.1192/bjp.184.47.s55
 
Joffe BI, Panz VR, Wing JR, Raal FJ, Seftel HC (1992). Pathogenesis of noninsulin- dependent diabetes mellitus in the black population of southern Africa. Lancet. 340(8817):460-462.
http://dx.doi.org/10.1016/0140-6736(92)91777-6
 
Kahu RC, White MF (1988). The insulin receptor and the molecular mechanism of insulin action. J. Clin. Invest. 82:1151.
http://dx.doi.org/10.1172/JCI113711
PMid:3049671 PMCid:PMC442664
 
Kaku K (2010). Pathophysiology of type 2 diabetes and its treatment policy. JMAJ, 53(1):41-46.
 
Karvonen M, Pitkaniemi J, Tuomilehto J (1999). The onset age of type 1 diabetes in Finnish children has become younger. The Finnish childhood diabetes Registry Group. Diabetes care. 22:1066-1070.
http://dx.doi.org/10.2337/diacare.22.7.1066
PMid:10388969
 
Knowler WC, Nelson RG, Saad MF, Bennett PH, Pettitt DJ (1993). Determinants of diabetes mellitus in the Pima Indians. Diabetes Care. 16:216-227.
http://dx.doi.org/10.2337/diacare.16.1.216
PMid:8422779
 
Knowler WC, Pettitt DJ, Sadd M, Bennett PH (1990). Diabetes mellitus in the Pina Indians: incidence, risk factors and pathogenesis. Diabetes/Metab.Rev 6:1-27.
http://dx.doi.org/10.1002/dmr.5610060101
PMid:2192853
 
Kolb, H, Kolb-bachofen (1992). Nitric oxide a pathogenetic factor in autoimmunity. Immunol. Today, 13:157-159.
http://dx.doi.org/10.1016/0167-5699(92)90118-Q
 
Kolb-bachofen V, Epstein SQ, Kiesel U, Kolb H (1988). Low dose streptozocin induced diabetes in mice. Electron microscopy reveals single-cells insulitis before diabetes onset. Diabetes. 37:21-27.
http://dx.doi.org/10.2337/diab.37.1.21
http://dx.doi.org/10.2337/diabetes.37.1.21
PMid:3275555
 
Kroncke KD, Kolb-bachofen V, Berschick B, Burkart V, Kolb H (1991). Activated macrophages kill pancreatic syngeneic islet via arginine-dependent nitric oxide generation. Biochem. Biophys. Res. Commun.175:752-758.
http://dx.doi.org/10.1016/0006-291X(91)91630-U
 
Levy JR, Hug V (1993). Nuclear protein-binding analysis of a GC-rich insulin-receptor promotor regulator region. Diabetes, 42: 66-73.
http://dx.doi.org/10.2337/diabetes.42.1.66
http://dx.doi.org/10.2337/diab.42.1.66
PMid:8380564
 
Lukic ML, Al-sharif R, Mostarica M, Bahr G, Behbehani K (1991). Immunological basis of the strain differences in susceptibility to low-dose streptozotocininduced diabetes in rats. In: Lymphatic Tissues and In vivo Immune Responses . Eds. Imhof. et al.; New York. Marcel Dekker Inc. pp 643-647.
 
Lukic ML, Stosic-Grujicic S, Ostojic N, Chan WL, Liew FY (1991). Inhibition of nitric oxide generation affects the induction of diabetes by streptozotocin in mice. Biochem. Biophys. Res. Commun. 178:913-920.
http://dx.doi.org/10.1016/0006-291X(91)90978-G
 
Mandrup-poulsen T, Spinas GA, Prowse SJ, Hansen BS, Jorgensen DW, Bendtzen K, Nielsen JH, Nerup J (1987). Islet cytotoxicity of interleukin-l. Influence of culture conditions and islet donor characteristics. Diabetes, 1987;36:641-647.
http://dx.doi.org/10.2337/diab.36.5.641
http://dx.doi.org/10.2337/diabetes.36.5.641
PMid:3552796
 
McVeigh GE, Brennan GM, Johnston GD, McDermott BJ, McGrath LT, Henry WR, Andrews JW, Hayes JR (1993). Dietary fish oil augments nitric oxide production or release in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 36:33.-38.
 
Molina JM, Cooper GIS, Leighton B, Olefsky JM (1990). Induction of insulin resistance in vivo by amylin and calcitonin gene-related peptide. Diabetes. 39:260-5.
http://dx.doi.org/10.2337/diab.39.2.260
http://dx.doi.org/10.2337/diabetes.39.2.260
PMid:2227135
 
Mueckler M (1990). Family of glucose-transporter genes: implications for glucose homeostasis and diabetes. Diabetes. 39:6-11.
http://dx.doi.org/10.2337/diabetes.39.1.6
http://dx.doi.org/10.2337/diacare.39.1.6
PMid:2210061
 
National Diabetes Data Group (1979). Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes. 28:1039-1057.
http://dx.doi.org/10.2337/diab.28.12.1039
PMid:510803
 
Neil HA, Gatling W, Mather HM, Thompson AV, Thorogood M, Fowler GH, Hill RD, Mann JI (1987). The Oxford community Diabetes study; evidence for an increase in the prevalence of known diabetes in Great Britain. Diabetic Med. 4:539-543.
http://dx.doi.org/10.1111/j.1464-5491.1987.tb00926.x
PMid:2962810
 
Njolstad PR, Sagen JV, Bjorkhaug L, Odili S, Shehadeh N, Bakry D, Sarici, S. U., Alpay, F., Molnes, J., Molven, A., Sovik, O. and Matschinsky, F. M. (2003). Permanent neonatal diabetes caused by glucokinase deficiency: inborn error of the glucose-insulin signaling pathway. Diabetes. 52(11):2854-60.
http://dx.doi.org/10.2337/diabetes.52.11.2854
PMid:14578306
 
Wilson PW, Mcghee DL, Kannel WB (1981). Obesity, very low density lipoproteins and glucose intolerance over fourteen years: the Framingham study. Am. J. Epidemiol. 114:697-704.
PMid:7304597
 
Oelbaum RS (1992). Analysis of three glucose transporter genes in a Caucasian population:no associations with non insulin-dependent diabetes and obesity. Clin. Genet. 42:260- 266.
http://dx.doi.org/10.1111/j.1399-0004.1992.tb03252.x
PMid:1362530
 
Ohagi S, Ekawa K, Sanke K, Nishi M, Nanjo K (1992). Restriction fragment length polymorphisms near the islet amyloid polypeptide gene in Japanese subjects. Diabetes Res. Clin. Pract.18:71-74
http://dx.doi.org/10.1016/0168-8227(92)90001-8
 
Raju SM, Raju B (2010). Illustrated medical biochemistry. 2nd Edition. Jaypee Brothers Medical Publishers ltd, New Delhi, India. 645pp
 
Richens ER, Abdella N, Jayyab AK., Alsaffar M, Behbehani K (1988); Type 2 Diabetes in Arab patients in Kuwait. Diabetic Med. 5:231-234.
 
Type 2 Diabetes in Arab patients in Kuwait. Diabetic Med. 5:231-234.
http://dx.doi.org/10.1111/j.1464-5491.1988.tb00975.x
PMid:2967143
 
Rowley WR, Bezold C. (2012)."Creating public awareness: state 2025 diabetes forecasts." Population Health Management. 15.
http://dx.doi.org/10.1089/pop.2011.0053
PMid:22283662
 
Shaw JE, Sicree RA, Zimmet PZ (2010). Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res. Clin. Pract. 87:4-14.
http://dx.doi.org/10.1016/j.diabres.2009.10.007
PMid:19896746
 
Steiner DF, Ohagi S, Nagamatsu S, Bell GI, Nishi M (1991). Is Islet Amyloid Polypeptide a Significant Factor in Pathogenesis or Pathphysiology of Diabetes. Diabetes. 40(3):305-309.
http://dx.doi.org/10.2337/diabetes.40.3.305
http://dx.doi.org/10.2337/diab.40.3.305
PMid:1999269
 
Sten-Linder M, Wedell A, Iselius L, Efendic S, Luft R, Luthman H (1993). DNA polymorphisms in the human tyrosine hydroxylase/insulin/insulin-like growth factor II chromosomal region in relation to glucose and insulin responses. Diabetologia. 36:25-32.
http://dx.doi.org/10.1007/BF00399089
PMid:8094694
 
Tattershall RB (1991). Maturity-onset diabetes of the young (MODY) in Pickup and Williams. Textbook of Diabetes. 1:246.
 
Ulaeto D, Lacy PE, Kipnis DM, Kanagawa O, Unanue ER (1992). A T-cell dormant state in the autoimmune process of non-obese diabetic mice treated with complete Freund's adjuvant. Proc. Natl. Acad. Sci. USA, 89:3927-3931.
http://dx.doi.org/10.1073/pnas.89.9.3927
PMid:1570315 PMCid:PMC525604
 
Vionnet N, Stoffel M, Takeda J, Yasuda K, Bell GI, Zouali H, Lesage S, Velho G, Iris F, Passa P (1992). Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus. Nature. 356:721-722.
http://dx.doi.org/10.1038/356721a0
PMid:1570017
 
Vuorinen-Markkola H, Koivisto VA, Ykijarvinen H (1992). Mechanisms of hyperglycemia-induced insulin resistance in whole body and skeletal muscle of type 1 diabetic patients. Diabetes. 41:571-580.
http://dx.doi.org/10.2337/diab.41.5.571
http://dx.doi.org/10.2337/diabetes.41.5.571
PMid:1568526
 
Westermark P (1973). Fine Structure of Islets of Langerhans in Insular Amyloidosis. Vichows Arch. Path. Anat. 359:1-18.
http://dx.doi.org/10.1007/BF00549079
 
Yagi H, Matsumoto M, Kunimoto K, Kawaguchi J, Makino S, Harada M (1992). Analysis of the roles of CD4+ T cells in autoimmune diabetes of NOD mice using transfer to NOD male mice. Eur. J. Immunol. 22:2387-2393.
http://dx.doi.org/10.1002/eji.1830220931
PMid:1516628
 
Zavala AV, Fabiano de Bruno LE, Cardoso AI, Mota AH, Capucchio M, Poskus E, Fainboim L, Basabe JC (1992). Cellular and humoural autoimmunity markers in Type 2 (non-insulin-dependent.) diabetic patients with secondary drug failure. Diabetologia. 35:1159-1164.
http://dx.doi.org/10.1007/BF00401370
PMid:1478368

 


APA (2013). The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus. Journal of Physiology and Pathophysiology, 4(4), 46-57.
Chicago Ozougwu, J. C., Obimba, K. C., Belonwu, C. D., and Unakalamba, C. B.. "The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus." Journal of Physiology and Pathophysiology 4, no. 4 (2013): 46-57.
MLA Ozougwu, et al. "The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus." Journal of Physiology and Pathophysiology 4.4 (2013): 46-57.
   
DOI 10.5897/JPAP2013.0001
URL http://academicjournals.org/journal/JPAP/article-abstract/974E7B515872

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