The changes in insulin resistance and insulin secretion and their association with changes in glucose regulation status in Asians with prediabetes remain uncertain.
Materials and Methods
We included Korean adults (aged 20-79 years) with prediabetes who underwent routine medical check-ups at a mean interval of 5 years. Prediabetes was defined as fasting plasma glucose (FPG) 5.6-6.9 mmol/l or HbA1c 5.7-6.4% (39-46 mmol/mol). Insulin resistance (HOMA-IR) and beta-cell function (HOMA-%B) indices were assessed by homeostasis model assessment. Incident diabetes was defined as FPG ≥ 7.0 mmol/l, HbA1c ≥ 6.5% (48 mmol/mol), or initiation of antidiabetic medications.
Among the 7,208 participants with prediabetes, 4,410 (61.2%) remained as prediabetes (control group), 2,123 (29.5%) reverted to normal glucose regulation (regressors), and 675 (9.4%) progressed to type 2 diabetes (progressors) after 5 years. Compared with the control group, the progressors had higher baseline HOMA-IR (2.48 ± 1.45 versus 2.06 ± 1.20, P < 0.001), but similar baseline HOMA-%B (74.6 ± 47.6 versus 73.1 ± 41.4, P=0.68). By contrast, the regressors had lower baseline HOMA-IR (1.98 ± 1.14 versus 2.06 ± 1.20, P = 0.035) but higher baseline HOMA-%B (77.4 ± 43.1 versus 73.1 ± 41.4, P = 0.001). After 5 years, the progressors showed a 31% increase in HOMA-IR (2.48 ± 1.45 versus 3.24 ± 2.10, P < 0.001) and 15% decrease in HOMA-%B (74.6 ± 47.6 versus 63.8 ± 40.4, P < 0.001), whereas the regressors showed 29% decrease in HOMA-IR (1.98 ± 1.14 versus 1.41 ± 0.78, P < 0.001) and 4% increase in HOMA-%B (77.4 ± 43.1 versus 80.2 ± 47.9, P = 0.010).
Although increase in insulin resistance and decrease in beta-cell function both contributed to the progression to type 2 diabetes from prediabetes, longitudinal change in insulin resistance was the predominant factor in Koreans.
Key Indexing Terms
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to The American Journal of the Medical Sciences
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Classification and diagnosis of diabetes.Diabetes Care. 2016; 39: S13-S22
- Pathogenesis of type 2 diabetes mellitus.Med Clin North Am. 2004; 88: 787-835
- Contributions of insulin-resistance and insulin-secretory defects to the pathogenesis of type 2 diabetes mellitus.Mayo Clin Proc. 2003; 78: 447-456
- Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose.Diabetes Care. 2006; 29: 1130-1139
- Coordinate changes in plasma glucose and pancreatic beta-cell function in Latino women at high risk for type 2 diabetes.Diabetes. 2006; 55: 1074-1079
- Natural history of insulin sensitivity and insulin secretion in the progression from normal glucose tolerance to impaired fasting glycemia and impaired glucose tolerance: the Inter99 study.Diabetes Care. 2009; 32: 439-444
- Fasting tests of insulin secretion and sensitivity predict future prediabetes in Japanese with normal glucose tolerance.J Diabetes Investig. 2010; 1: 191-195
- The changes in early phase insulin secretion in newly diagnosed, drug naive Korean prediabetes subjects.Korean Diabetes J. 2010; 34: 157-165
- Evidence of reduced beta-cell function in Asian Indians with mild dysglycemia.Diabetes Care. 2013; 36: 2772-2778
- The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus.J Clin Invest. 1999; 104: 787-794
- The natural course of beta-cell function in nondiabetic and diabetic individuals: the Insulin Resistance Atherosclerosis Study.Diabetes. 2006; 55: 1114-1120
- Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study.Lancet. 2009; 373: 2215-2221
- Ageing and type 2 diabetes in an elderly Chinese population: the role of insulin resistance and beta cell dysfunction.Eur Rev Med Pharmacol Sci. 2014; 18: 1790-1797
- Predictors of and longitudinal changes in insulin sensitivity and secretion preceding onset of type 2 diabetes.Diabetes. 2005; 54: 166-174
- Progressive loss of beta-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes.Diabetes Care. 2007; 30: 677-682
- Impact of impaired insulin secretion and insulin resistance on the incidence of type 2 diabetes mellitus in a Japanese population: the Saku study.Diabetologia. 2013; 56: 1671-1679
- Ethnic disparities in the association of impaired fasting glucose with the 10-year cumulative incidence of type 2 diabetes.Diabetes Res Clin Pract. 2014; 103: 127-132
- Incidence rates and predictors of diabetes in those with prediabetes: the Strong Heart Study.Diabetes Metab Res Rev. 2010; 26: 378-385
- Glucose tolerance, insulin secretion, and insulin sensitivity in nonobese and obese Japanese subjects.Diabetes Care. 1997; 20: 1562-1568
- Insulin secretory dysfunction and insulin resistance in the pathogenesis of Korean type 2 diabetes mellitus.Metabolism. 2001; 50: 590-593
- Early insulin secretion failure leads to diabetes in Chinese subjects with impaired glucose regulation.Diabetes Metab Res Rev. 2009; 25: 144-149
- Relative contributions of insulin resistance and beta-cell dysfunction to the development of Type 2 diabetes in Koreans.Diabet Med. 2013; 30: 1075-1079
- 10-year trajectory of beta-cell function and insulin sensitivity in the development of type 2 diabetes: a community-based prospective cohort study.Lancet Diabetes Endocrinol. 2016; 4: 27-34
- Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes.Diabetes Res Clin Pract. 2014; 106: 351-359
- Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.Diabetologia. 1985; 28: 412-419
- Decreased beta cell function and insulin sensitivity contributed to increasing fasting glucose in Chinese.Acta Diabetol. 2012; 49: S51-S58
- Increase in homeostasis model assessment of insulin resistance (HOMA-IR) had a strong impact on the development of type 2 diabetes in Japanese individuals with impaired insulin secretion: the Saku study.PLoS One. 2014; 9: e105827
- Insulin secretion and insulin resistance in newly diagnosed, drug naive prediabetes and type 2 diabetes patients with/without metabolic syndrome.Diabetes Res Clin Pract. 2007; 76: 397-403
- Changing clinical characteristics according to insulin resistance and insulin secretion in newly diagnosed type 2 diabetic patients in Korea.Diabetes Metab J. 2015; 39: 387-394
- The insulin resistance but not the insulin secretion parameters have changed in the Korean population during the last decade.Diabetes Metab J. 2015; 39: 117-125
- Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?.Diabetologia. 2009; 52: 1714-1723
- Impaired early- but not late-phase insulin secretion in subjects with impaired fasting glucose.Acta Diabetol. 2011; 48: 209-217
- Insulin secretory defect and insulin resistance in isolated impaired fasting glucose and isolated impaired glucose tolerance.J Diabetes Res. 2016; 2016 ()
- Use of HbA1c for diagnoses of diabetes and prediabetes: comparison with diagnoses based on fasting and 2-hr glucose values and effects of gender, race, and age.Metab Syndr Relat Disord. 2014; 12: 258-268
- Impact of hemoglobin A1c-based criterion on diagnosis of prediabetes: the Korea National Health and Nutrition Examination Survey 2011.J Diabetes Investig. 2015; 6: 51-55
- Prevalence of prediabetes and undiagnosed diabetes in Canada (2007-2011) according to fasting plasma glucose and HbA1c screening criteria.Diabetes Care. 2015; 38: 1299-1305
- Pathogenetic mechanisms and cardiovascular risk: differences between HbA(1c) and oral glucose tolerance test for the diagnosis of glucose tolerance.Diabetes Care. 2012; 35: 2607-2612
- Glucoregulatory function among African Americans and European Americans with normal or pre-diabetic hemoglobin A1c levels.Metabolism. 2014; 63: 767-772
- Pathogenesis of prediabetes: role of the liver in isolated fasting hyperglycemia and combined fasting and postprandial hyperglycemia.J Clin Endocrinol Metab. 2013; 98: E409-E417
- Pathogenesis of pre-diabetes: mechanisms of fasting and postprandial hyperglycemia in people with impaired fasting glucose and/or impaired glucose tolerance.Diabetes. 2006; 55: 3536-3549
Published online: October 16, 2017
Accepted: September 25, 2017
Received in revised form: September 19, 2017
Received: April 14, 2017
☆This work was presented as a poster in the 52nd European Association for the Study of Diabetes (EASD) Annual Meeting which was held in Munich, Germany on 12-16 September 2016.
☆☆The authors have no financial or other conflicts of interest to disclose.
© 2017 Southern Society for Clinical Investigation. Published by All rights reserved.