Review article: Biomedical intelligence
Vol. 142 No. 2930 (2012)
Diabetes mellitus Type 2 – the new face of an old lady
- Katharina Timper
- Marc Y Donath
Summary
Already 600 years before Christ, type 2 diabetes was known as a disease of elevated blood sugar levels associated with obesity. Since then, it appears, our understanding of the disease has not changed much, aside from the replacement of tasting the patients’ urine [1] by the measurement of plasma glucose and glycated haemoglobin levels (HbA1c) [2] for its diagnosis and the discovery of some new drugs. Already, in those old days a physician from India named Sushrut described diabetes mellitus as a disease characterised by the passage of large amounts of urine and its “honey-like” taste and, noteworthy, as a disease that is mainly associated with obesity and a sedentary lifestyle, recommending physical activity as the primary treatment option [3]. Although these milestone observations remain valid, major progress in the underlying pathogenesis of type 2 diabetes has been achieved showing a new face of this old disease and opening doors for novel treatment options.
This review will highlight recent pathophysiological aspects of type 2 diabetes, actual diagnostic and treatment guidelines and discuss some possible upcoming new therapeutic strategies.
References
- Dobson M. Nature of the urine in diabetes. Med Obs Inqu. 1776;5:298–310.
- Sacks DB, Arnold M, Bakris GL, Bruns DE, Horvath AR, et al. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Diabetes Care. 2011;34:e61–99.
- Major RH. A history of Medicine (Blackwell Scientific, Oxford, UK) 1954;1:74–91.
- Kahn BB. Type 2 diabetes: when insulin secretion fails to compensate for insulin resistance. Cell. 1998;92:593–6.
- Rhodes CJ. Type 2 diabetes-a matter of beta-cell life and death? Science. 2005;307:380–4.
- Robertson RP. Consequences on beta-cell function and reserve after long-term pancreas transplantation. Diabetes. 2004;53:633–44.
- Weir GC, Bonner-Weir S. Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes. 2004;53(Suppl 3):S16–21.
- Prentki M, Nolan CJ. Islet beta cell failure in type 2 diabetes. J Clin Invest. 2006;116:1802–12.
- Hull RL, Westermark GT, Westermark P, Kahn SE. Islet amyloid: a critical entity in the pathogenesis of type 2 diabetes. J Clin Endocrinol Meta. 2004;89:3629–43.
- Harding HP, Ron D. Endoplasmic reticulum stress and the development of diabetes: a review. Diabetes. 2002;51(Suppl 3):S455–61.
- Hotamisligil GS, Erbay E. Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol. 2008;8:923–34.
- Donath MY, Storling J, Maedler K, Mandrup-Poulsen T. Inflammatory mediators and islet beta-cell failure: a link between type 1 and type 2 diabetes. J Mol Med. (Berl) 2003;81:455–70.
- Ehses JA, Ellingsgaard H, Boni-Schnetzler M, Donath MY. Pancreatic islet inflammation in type 2 diabetes: from alpha and beta cell compensation to dysfunction. Arch Physiol Biochem. 2009;115:240–7.
- Donath MY, Schumann DM, Faulenbach M, Ellingsgaard H, Perren A, et al. Islet inflammation in type 2 diabetes: from metabolic stress to therapy. Diabetes Care. 2008;31(Suppl 2):S161–4.
- Masters SL, Dunne A, Subramanian SL, Hull RL, Tannahill GM, et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1beta in type 2 diabetes. Nat Immunol. 2010;11:897–904.
- Clausen TD, Mathiesen ER, Hansen T, Pedersen O, Jensen DM, et al. High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes: the role of intrauterine hyperglycemia. Diabetes Care. 2008;31:340–6.
- Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(Suppl 1):S62–9.
- International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009;32:1327–34.
- Timper K, Holber A, Beyrau R, Meienberg F. Fallstricke bei der Bestimmung von HbA1c. Swiss Medical Forum. 2012(23);12:466–9.
- Stettler C, Mueller B, Diem P. What you always wanted to know about HbA1c. Schweiz Med Wochenschr. 2000;130:993–1005.
- American Diabetes A. Standards of medical care in diabetes – 2012. Diabetes Care. 2012;35(Suppl 1):S11–63.
- Zhang X, Gregg EW, Williamson DF, Barker LE, Thomas W, et al. A1C level and future risk of diabetes: a systematic review. Diabetes Care. 2010;33:1665–73.
- Ferrannini E, Nannipieri M, Williams K, Gonzales C, Haffner SM, et al. Mode of onset of type 2 diabetes from normal or impaired glucose tolerance. Diabetes. 2004;53:160–5.
- The prevalence of retinopathy in impaired glucose tolerance and recent-onset diabetes in the Diabetes Prevention Program. Diabet Med. 2007;24:137–44.
- Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999;22:233–40.
- Ning F, Tuomilehto J, Pyorala K, Onat A, Soderberg S, et al. Cardiovascular disease mortality in Europeans in relation to fasting and 2-h plasma glucose levels within a normoglycemic range. Diabetes Care. 2010;33:2211–6.
- Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group. Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe. Lancet. 1999;354:617–21.
- Selvin E, Steffes MW, Zhu H, Matsushita K, Wagenknecht L, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med. 2010;362:800–11.
- Standards of medical care in diabetes – 2011. Diabetes Care. 2011;34(Suppl 1):S11–61.
- Tsapas A, Matthews DR. N of 1 trials in diabetes: making individual therapeutic decisions. Diabetologia. 2008;51:921–5.
- Shah ND, Mullan RJ, Breslin M, Yawn BP, Ting HH, et al. Translating comparative effectiveness into practice: the case of diabetes medications. Med Care. 2010;48:S153–8.
- Nathan DM, Davidson MB, DeFronzo RA, Heine RJ, Henry RR, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care. 2007;30:753–9.
- (Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837–53.
- Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364–79.
- Elmer PJ, Obarzanek E, Vollmer WM, Simons-Morton D, Stevens VJ, et al. Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial. Ann Intern Med. 2006;144:485–95.
- Anderson JW, Kendall CW, Jenkins DJ. Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. J Am Coll Nutr. 2003;22:331–9.
- Klein S, Sheard NF, Pi-Sunyer X, Daly A, Wylie-Rosett J, et al. Weight management through lifestyle modification for the prevention and management of type 2 diabetes: rationale and strategies: a statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition. Diabetes Care. 2004;27:2067–73.
- Ellingsgaard H, Hauselmann I, Schuler B, Habib AM, Baggio LL, et al. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat Med. 2011;17:1481–9.
- Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577–89.
- Boussageon R, Supper I, Bejan-Angoulvant T, Kellou N, Cucherat M, et al. Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials. PLoS Med 2012;9: e1001204.
- Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193–203.
- Sanders LJ. From Thebes to Toronto and the 21st Century: An Incredible Journey. Diabetes Spectrum. 2002;15:56–60.
- Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet Med. 2010;27:136–42.
- Wright EM, Hirayama BA, Loo DF. Active sugar transport in health and disease. J Intern Med. 2007;261:32–43.
- Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care. 2010;33:2217–24.
- Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375:2223–33.
- Nauck MA, Del Prato S, Meier JJ, Duran-Garcia S, Rohwedder K, et al. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care. 2011;34:2015–22.
- Wilding JP, Norwood P, T’Joen C, Bastien A, List JF, et al. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment. Diabetes Care. 2009;32:1656–62.
- Bristol-Myers Squibb A. (2011) U.S. Food and Drug Administration Endocrinologic & Metabolic Advisory Committee Background Document: Dapagliflozin, BMS-512148, NDA 202293. Princeton, NJ: Bristol-Myers Squibb. pp. 1–224.
- Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg 1995;222:339–50; discussion 350–32.
- Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122:248–56 e245.
- Schauer PR, Burguera B, Ikramuddin S, Cottam D, Gourash W, et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg. 2003;238:467–84; discussion 484–465.
- Pournaras DJ, le Roux CW. Obesity, gut hormones, and bariatric surgery. World J Surg. 2009;33:1983–8.
- Laferrere B, Teixeira J, McGinty J, Tran H, Egger JR, et al. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab. 2008;93:2479–85.
- Buchwald H, Estok R, Fahrbach K, Banel D, Sledge I. Trends in mortality in bariatric surgery: a systematic review and meta-analysis. Surgery. 2007;142:621–32; discussion 632–625.
- Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11:98–107.
- Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.
- Xu H, Barnes GT, Yang Q, Tan G, Yang D, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112:1821–30.
- Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005;11:183–90.
- Dominguez H, Storgaard H, Rask-Madsen C, Steffen Hermann T, Ihlemann N, et al. Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes. J Vasc Res. 2005;42:517–25.
- Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;356:1517–26.
- Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care. 2008;31:289–94.
- Cavelti-Weder C, Babians-Brunner A, Keller C, Stahel MA, Kurz-Levin M, et al. (2012) Effects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes. Diabetes Care. In press for July 2012.