Medical Conditions Associated with Type 2 Diabetes

Medical Conditions Associated with Type 2 Diabetes

While there are various clinical, lifestyle, and demographic risk factors that increase the risk of developing type 2 diabetes (T2D), certain medical conditions are also known to be commonly associated with T2D. Conditions like cardiovascular disease, metabolic syndrome, gestational diabetes, polycystic ovary syndrome, and hyperuricemia may share underlying pathogenic factors with T2D and thus are commonly seen in individuals with T2D.

 

CARDIOVASCULAR DISEASES (CVD) such as myocardial infarction (heart attack), heart failure, and stroke are known to be closely linked with T2D.1 CVD is the most prevalent cause of death in patients with T2D,2 and people with T2D are 2-4 times more likely to develop coronary artery disease and myocardial infarction.3 A review that analyzed 57 studies with a combined patient population of over 4.5 million found that, globally, CVD affected approximately 32.2% of patients with T2D.4 About 15% of patients with T2D was found to have heart failure, 10% myocardial infarction, and 7.6% stroke. CVD was found to contribute to almost half of all deaths in those studies. T2D and CVD share many common features, including insulin resistance, high blood pressure, obesity, and inflammation. There may be genetics links between the two diseases, though precisely how they are related on a genetic, epigenetic, and environmental level remains to be elucidated.3

 

METABOLIC SYNDROME (MetS) is defined as a set of 5 conditions that are associated with T2D, along with other health problems.5,6 The 5 conditions are high blood glucose levels, high blood pressure, abdominal obesity (measured by waist circumference), high triglyceride levels, and low HDL cholesterol levels. A patient may be identified as having MetS if 3 of the above 5 conditions are present.7 Studies have shown that patients with MetS have 5 times greater risk of developing T2D. Notably, a study published in 2020 involving more than 10 million patients in South Korea showed that a reduction in MetS or in any of its components was associated with a reduced risk of T2D. After adjusting for certain factors, improvements in the number of MetS components was found to decrease the risk of developing T2D by 36%. Reduction in fasting glucose levels decreased the risk by 46%, reduction in triglycerides by 27%, improvements in HDL-cholesterol by 24%, reduction in high blood pressure by 25%, and reduction in waist circumference by 8%.8

 

GESTATIONAL DIABETES (GDM) is a type of diabetes that develops during pregnancy.9 Studies have shown that women with GDM have 7 times greater risk of developing T2D when compared to women who had normoglycemic pregnancies.10 GDM and T2D share similar pathophysiology, explaining its high association. In most cases of GDM, prior asymptomatic insulin resistance and b-cell defects become clinically manifested when pregnancy exacerbates these conditions.11,12

 

POLYCYSTIC OVARY SYNDROME (PCOS) is a complex endocrine disorder that is characterized by 2 of the 3 diagnostic conditions: hyperandrogenism (high levels of androgen), polycystic ovaries, and ovulatory dysfunction.13,14 PCOS is linked with various metabolic defects, including T2D and MetS, as it shares many of the underlying pathophysiological features that mark these illnesses. People with PCOS have 4 times and 2 times greater risk of developing T2D and MetS, respectively. Nearly 50% of women with PCOS are obese and have a higher prevalence of dyslipidemia (abnormal lipid profile in the blood). Even though the exact pathogenesis of PCOS is still being researched, insulin resistance has been hypothesized as a key factor, in addition to altered hormone levels and possible predisposition to hyperandrogenism.

 

HYPERURICEMIA is defined as having a serum uric acid concentration of >7mg/dL, a condition that predisposes individuals to gout (a form of arthritis caused by uric acid crystal buildup in the joints) and kidney stones.15 Both T2D and hyperuricemia are linked with hyperinsulinemia, and several prospective studies have shown that hyperuricemia is associated with an increased risk of developing T2D even after controlling for other T2D risk factors (eg, BMI, physical inactivity, smoking, alcohol).16–19 Even though the complex relationship between the two conditions is yet to be understood, studies suggest a bidirectional causal relationship between high serum uric acid level and insulin resistance and note that serum uric acid should be considered as a strong and independent risk factor for T2D.17,20

 

References:
1. Leon BM, Maddox TM. Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes. 2015;6(13):1246-1258. doi:10.4239/wjd.v6.i13.1246
2. Matheus AS de M, Tannus LRM, Cobas RA, Palma CCS, Negrato CA, Gomes M de B. Impact of Diabetes on Cardiovascular Disease: An Update. Int J Hypertens. 2013;2013:653789. doi:10.1155/2013/653789
3. De Rosa S, Arcidiacono B, Chiefari E, Brunetti A, Indolfi C, Foti DP. Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links. Frontiers in Endocrinology. 2018;9. Accessed April 12, 2022. https://www.frontiersin.org/article/10.3389/fendo.2018.00002
4. Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovascular Diabetology. 2018;17(1):83. doi:10.1186/s12933-018-0728-6
5. Shin J, Lee J, Lim S, et al. Metabolic syndrome as a predictor of type 2 diabetes, and its clinical interpretations and usefulness. J Diabetes Investig. 2013;4(4):334-343. doi:10.1111/jdi.12075
6. About Metabolic Syndrome. www.heart.org. Accessed April 12, 2022. https://www.heart.org/en/health-topics/metabolic-syndrome/about-metabolic-syndrome
7. Regufe VMG, Pinto CMCB, Perez PMVHC. Metabolic syndrome in type 2 diabetic patients: a review of current evidence. Porto Biomedical Journal. 2020;5(6):e101. doi:10.1097/j.pbj.0000000000000101
8. Lee MK, Han K, Kim MK, et al. Changes in metabolic syndrome and its components and the risk of type 2 diabetes: a nationwide cohort study. Sci Rep. 2020;10(1):2313. doi:10.1038/s41598-020-59203-z
9. Egan AM, Dow ML, Vella A. A Review of the Pathophysiology and Management of Diabetes in Pregnancy. Mayo Clinic Proceedings. 2020;95(12):2734-2746. doi:10.1016/j.mayocp.2020.02.019
10. McIntyre HD, Catalano P, Zhang C, Desoye G, Mathiesen ER, Damm P. Gestational diabetes mellitus. Nat Rev Dis Primers. 2019;5(1):1-19. doi:10.1038/s41572-019-0098-8
11. Buchanan TA. Pancreatic B-Cell Defects in Gestational Diabetes: Implications for the Pathogenesis and Prevention of Type 2 Diabetes. The Journal of Clinical Endocrinology & Metabolism. 2001;86(3):989-993. doi:10.1210/jcem.86.3.7339
12. Catalano PM, Huston L, Amini SB, Kalhan SC. Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus. American Journal of Obstetrics and Gynecology. 1999;180(4):903-916. doi:10.1016/S0002-9378(99)70662-9
13. Williams T, Mortada R, Porter S. Diagnosis and Treatment of Polycystic Ovary Syndrome. AFP. 2016;94(2):106-113.
14. Pelusi B, Gambineri A, Pasquali R. Type 2 diabetes and the polycystic ovary syndrome. Minerva Ginecol. 2004;56(1):41-51.
15. Harris MD, Siegel LB, Alloway JA. Gout and Hyperuricemia. AFP. 1999;59(4):925.
16. Bhole V, Choi JWJ, Kim SW, de Vera M, Choi H. Serum uric acid levels and the risk of type 2 diabetes: a prospective study. Am J Med. 2010;123(10):957-961. doi:10.1016/j.amjmed.2010.03.027
17. Dehghan A, van Hoek M, Sijbrands EJG, Hofman A, Witteman JCM. High serum uric acid as a novel risk factor for type 2 diabetes. Diabetes Care. 2008;31(2):361-362. doi:10.2337/dc07-1276
18. Kramer CK, von Mühlen D, Jassal SK, Barrett-Connor E. Serum uric acid levels improve prediction of incident type 2 diabetes in individuals with impaired fasting glucose: the Rancho Bernardo Study. Diabetes Care. 2009;32(7):1272-1273. doi:10.2337/dc09-0275
19. Niskanen L, Laaksonen DE, Lindström J, et al. Serum uric acid as a harbinger of metabolic outcome in subjects with impaired glucose tolerance: the Finnish Diabetes Prevention Study. Diabetes Care. 2006;29(3):709-711. doi:10.2337/diacare.29.03.06.dc05-1465
20. Li C, Hsieh MC, Chang SJ. Metabolic syndrome, diabetes, and hyperuricemia. Current Opinion in Rheumatology. 2013;25(2):210-216. doi:10.1097/BOR.0b013e32835d951e

  

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