Review Article
The metabolic deterioration that antedates diabetes: personal trajectories of HbA1c and fasting glucose as early indicators and possible triggers for intervention
Rachel Dankner,
Michael Bergman,
Ann Danoff,
Sana Qureshi,
Ian Whitford,
Nargess Kaviani,
Yevgeniya Dynkevich,
Jesse Roth,
Corresponding Author
Rachel Dankner
The Gertner Institute for Epidemiology and Health Policy Research, Chaim Sheba Medical Center, Tel Hashomer, Israel
Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine School of Public Health, Tel Aviv University, Ramat Aviv, Israel
Laboratory of Diabetes and Metabolic Disorders, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA
Rachel Dankner, The Gertner Institute for Epidemiology and Health Policy Research, Chaim Sheba Medical Center, Tel Hashomer, Israel.
E-mail: [email protected]
Search for more papers by this authorMichael Bergman
New York University School of Medicine, New York, NY, USA
Search for more papers by this authorAnn Danoff
New York University School of Medicine, New York, NY, USA
Search for more papers by this authorSana Qureshi
Laboratory of Diabetes and Metabolic Disorders, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA
Search for more papers by this authorIan Whitford
Laboratory of Diabetes and Metabolic Disorders, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA
Search for more papers by this authorNargess Kaviani
Division of Endocrinology, Diabetes and Metabolism, North Shore-Long Island Jewish Health System, Lake Success, NY, USA
Search for more papers by this authorYevgeniya Dynkevich
Queens Long Island Medical Group, North Shore-Long Island Jewish Health System, Hicksville, NY, USA
Search for more papers by this authorJesse Roth
Laboratory of Diabetes and Metabolic Disorders, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA
Hofstra North Shore-LIJ School of Medicine, North Shore-Long Island Jewish Health System, Manhasset, NY, USA
Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA
Search for more papers by this authorRachel Dankner,
Michael Bergman,
Ann Danoff,
Sana Qureshi,
Ian Whitford,
Nargess Kaviani,
Yevgeniya Dynkevich,
Jesse Roth,
Corresponding Author
Rachel Dankner
The Gertner Institute for Epidemiology and Health Policy Research, Chaim Sheba Medical Center, Tel Hashomer, Israel
Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine School of Public Health, Tel Aviv University, Ramat Aviv, Israel
Laboratory of Diabetes and Metabolic Disorders, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA
Rachel Dankner, The Gertner Institute for Epidemiology and Health Policy Research, Chaim Sheba Medical Center, Tel Hashomer, Israel.
E-mail: [email protected]
Search for more papers by this authorMichael Bergman
New York University School of Medicine, New York, NY, USA
Search for more papers by this authorAnn Danoff
New York University School of Medicine, New York, NY, USA
Search for more papers by this authorSana Qureshi
Laboratory of Diabetes and Metabolic Disorders, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA
Search for more papers by this authorIan Whitford
Laboratory of Diabetes and Metabolic Disorders, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA
Search for more papers by this authorNargess Kaviani
Division of Endocrinology, Diabetes and Metabolism, North Shore-Long Island Jewish Health System, Lake Success, NY, USA
Search for more papers by this authorYevgeniya Dynkevich
Queens Long Island Medical Group, North Shore-Long Island Jewish Health System, Hicksville, NY, USA
Search for more papers by this authorJesse Roth
Laboratory of Diabetes and Metabolic Disorders, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA
Hofstra North Shore-LIJ School of Medicine, North Shore-Long Island Jewish Health System, Manhasset, NY, USA
Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA
Search for more papers by this authorSummary
HbA1c testing has become an accepted means of diagnosing diabetes as an alternative to blood glucose levels. However, population-based norms of glucose and of HbA1c levels do not enable the detection of diabetes at an early enough stage to thwart complications. Personal trajectories of glucose levels show steep increases a number of years prior to diabetes diagnosis. Here, we hypothesize that a comparable time-dependent deviation in an individual's HbA1c level may be an early manifestation of disease that should prompt lifestyle modifications. We predict that analysis of personal trajectories of glucose and of HbA1c will promote earlier intervention and a greater reduction in disease complications than current standards, which are based on population-based norms. Copyright © 2012 John Wiley & Sons, Ltd.
References
- 1 Gawande A. 2007. Better: a surgeon's notes on performance. Metropolitan Books, Henry Holt and Company, New York.
- 2 Dankner R, Danoff A, Roth J. Can ‘personalized diagnostics’ promote earlier intervention for dysglycaemia? Hypothesis ready for testing. Diabetes Metab Res Rev 2010; 26: 7–9.
- 3 Shanik MH, Xu Y, Skrha J, Dankner R, Zick Y, Roth J. Insulin resistance and hyperinsulinemia: is hyperinsulinemia the cart or the horse? Diabetes Care 2008; 31(Suppl 2): S262–268.
- 4
Dankner R,
Roth J. Predicting diabetes. In Prevention of Type 2 Diabetes, D LeRoith (ed). Springer: New York, 2012; 81–102.
10.1007/978-1-4614-3314-9_6 Google Scholar
- 5 Dankner R, Chetrit A, Shanik MH, Raz I, Roth J. Basal-state hyperinsulinemia in healthy normoglycemic adults is predictive of type 2 diabetes over a 24-year follow-up: a preliminary report. Diabetes Care 2009; 32: 1464–1466.
- 6 Roth J, Qiang X, Marban SL, Redelt H, Lowell BC. The obesity pandemic: where have we been and where are we going? Obes Res 2004; 12(Suppl 2): 88S–101S.
- 7 Novak V, Zhao P, Manor B, et al. Adhesion molecules, altered vasoreactivity, and brain atrophy in type 2 diabetes. Diabetes Care 2011; 34: 2438–2441.
- 8 Kurra S, Siris E. Diabetes and bone health: the relationship between diabetes and osteoporosis-associated fractures. Diabetes Metab Res Rev 2011; 27: 430–435.
- 9 Chowdhry MF, Vohra HA, Galinanes M. Diabetes increases apoptosis and necrosis in both ischemic and nonischemic human myocardium: role of caspases and poly-adenosine diphosphate-ribose polymerase. J Thorac Cardiovasc Surg 2007; 134: 124–131, 131 e121-123.
- 10 van Elderen SG, de Roos A, de Craen AJ, et al. Progression of brain atrophy and cognitive decline in diabetes mellitus: a 3-year follow-up. Neurology 2010; 75: 997–1002.
- 11 Oumeish OY. Skin disorders in patients with diabetes. Clin Dermatol 2008; 26: 235–242.
- 12 Malecki MT. Genetics of type 2 diabetes mellitus. Diabetes Res Clin Pract 2005; 68(Suppl1): S10–S21.
- 13 Qi L, Hu FB, Hu G. Genes, environment, and interactions in prevention of type 2 diabetes: a focus on physical activity and lifestyle changes. Curr Mol Med 2008; 8: 519–532.
- 14 Hivert MF, Jablonski KA, Perreault L, et al. Updated genetic score based on 34 confirmed type 2 diabetes loci is associated with diabetes incidence and regression to normoglycemia in the Diabetes Prevention Program. Diabetes 2011; 60: 1340–1348.
- 15 Selvin E, Steffes MW, Zhu H, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med 2010; 362: 800–811.
- 16 Mata-Cases M, De Prado-Lacueva C, Salido-Valencia V, et al. Incidence of complications and mortality in a type 2 diabetes patient cohort study followed up from diagnosis in a primary healthcare centre. Int J Clin Pract 2011; 65: 299–307.
- 17 Tirosh A, Shai I, Tekes-Manova D, et al. Normal fasting plasma glucose levels and type 2 diabetes in young men. N Engl J Med 2005; 353: 1454–1462.
- 18 Perreault L, Pan Q, Mather KJ, et al. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet 2012; 379: 2243–2251.
- 19 Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977–986.
- 20 UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837–853.
- 21 Saudek CD, Herman WH, Sacks DB, Bergenstal RM, Edelman D, Davidson MB. A new look at screening and diagnosing diabetes mellitus. J Clin Endocr Metab 2008; 93: 2447–2453.
- 22 International Expert Committee. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 2009; 32: 1327–1334.
- 23 Bonora E, Tuomilehto J. The pros and cons of diagnosing diabetes with A1C. Diabetes Care 2011; 34(Suppl 2): S184–190.
- 24 Selvin E, Crainiceanu CM, Brancati FL, Coresh J. Short-term variability in measures of glycemia and implications for the classification of diabetes. Arch Intern Med 2007; 167: 1545–1551.
- 25 Mbanya JC, Henry RR, Smith U. Presidents' statement on WHO recommendation on HbA1c for diabetes diagnosis. Diabetes Res Clin Pract 2011; 93: 310–311.
- 26 Gallagher EJ, Le Roith D, Bloomgarden Z. Review of hemoglobin A(1c) in the management of diabetes. J Diabetes 2009; 1: 9–17.
- 27 Herman WH, Cohen RM. Hemoglobin A1c: teaching a new dog old tricks. Ann Intern Med 2010; 152: 815–817.
- 28 American Diabetes Association. Standards of medical care in diabetes – 2010. Diabetes Care 2010; 33(Suppl 1): S11–61.
- 29 Colagiuri S, Borch-Johnsen K. DETECT-2: early detection of type 2 diabetes and IGT. Diabetes Voice 2003; 48: 11–13.
- 30 Colagiuri S, Lee CM, Wong TY, et al. Glycemic thresholds for diabetes-specific retinopathy: implications for diagnostic criteria for diabetes. Diabetes Care 2011; 34: 145–150.
- 31 Choi SH, Kim TH, Lim S, Park KS, Jang HC, Cho NH. Hemoglobin A1c as a diagnostic tool for diabetes screening and new-onset diabetes prediction: a 6-year community-based prospective study. Diabetes Care 2011; 34: 944–949.
- 32 Bonora E, Kiechl S, Mayr A, et al. High-normal HbA1c is a strong predictor of type 2 diabetes in the general population. Diabetes Care 2011; 34: 1038–1040.
- 33 Carson AP, Reynolds K, Fonseca VA, Muntner P. Comparison of A1C and fasting glucose criteria to diagnose diabetes among US adults. Diabetes Care 2010; 33: 95–97.
- 34 Christensen DL, Witte DR, Kaduka L, et al. Moving to an A1C-based diagnosis of diabetes has a different impact on prevalence in different ethnic groups. Diabetes Care 2010; 33: 580–582.
- 35 Lorenzo C, Haffner SM. Performance characteristics of the new definition of diabetes: the insulin resistance atherosclerosis study. Diabetes Care 2010; 33: 335–337.
- 36 Olson DE, Rhee MK, Herrick K, Ziemer DC, Twombly JG, Phillips LS. Screening for diabetes and pre-diabetes with proposed A1C-based diagnostic criteria. Diabetes Care 2010; 33: 2184–2189.
- 37 Rathmann W, Kowall B, Tamayo T, et al. Hemoglobin A1c and glucose criteria identify different subjects as having type 2 diabetes in middle-aged and older populations: the KORA S4/F4 Study. Ann Med 2012; 44: 170–177.
- 38 Malkani S, Mordes JP. Implications of using hemoglobin A1C for diagnosing diabetes mellitus. Am J Med 2011; 124: 395–401.
- 39 Miranda JJ, Bernabe-Ortiz A, Stanojevic S, Malaga G, Gilman RH, Smeeth L. A1C as a diagnostic criteria for diabetes in low- and middle-income settings: evidence from Peru. PLoS One 2011; 6: e18069.
- 40 Cowie CC, Rust KF, Byrd-Holt DD, et al. Prevalence of diabetes and high risk for diabetes using A1C criteria in the US population in 1988–2006. Diabetes Care 2010; 33: 562–568.
- 41 Selvin E, Steffes MW, Gregg E, Brancati FL, Coresh J. Performance of A1C for the classification and prediction of diabetes. Diabetes Care 2011; 34: 84–89.
- 42 Lipska KJ, De Rekeneire N, Van Ness PH, et al. Identifying dysglycemic states in older adults: implications of the emerging use of hemoglobin A1c. J Clin Endocrinol Metab 2010; 95: 5289–5295.
- 43 Droumaguet C, Balkau B, Simon D, et al. Use of HbA1c in predicting progression to diabetes in French men and women: data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR). Diabetes Care 2006; 29: 1619–1625.
- 44 Lorenzo C, Wagenknecht LE, Hanley AJ, Rewers MJ, Karter AJ, Haffner SM. A1C between 5.7 and 6.4% as a marker for identifying pre-diabetes, insulin sensitivity and secretion, and cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care 2010; 33: 2104–2109.
- 45 Nowicka P, Santoro N, Liu H, et al. Utility of hemoglobin A(1c) for diagnosing prediabetes and diabetes in obese children and adolescents. Diabetes Care 2011; 34: 1306–1311.
- 46 Mann DM, Carson AP, Shimbo D, Fonseca V, Fox CS, Muntner P. Impact of A1C screening criterion on the diagnosis of pre-diabetes among US adults. Diabetes Care 2010; 33: 2190–2195.
- 47 Kamps JL, Hempe JM, Chalew SA. Racial disparity in A1C independent of mean blood glucose in children with type 1 diabetes. Diabetes Care 2010; 33: 1025–1027.
- 48 Cohen RM, Holmes YR, Chenier TC, Joiner CH. Discordance between HbA1c and fructosamine: evidence for a glycosylation gap and its relation to diabetic nephropathy. Diabetes Care 2003; 26: 163–167.
- 49 Heianza Y, Hara S, Arase Y, et al. HbA1c 5.7–6.4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan (TOPICS 3): a longitudinal cohort study. Lancet 2011; 378: 147–155.
- 50 Okosun IS, Davis-Smith M, Seale JP, Ngulefac J. Applicability of a combination of hemoglobin A1c and fasting plasma glucose in population-based prediabetes screening. J Diabetes 2012.
- 51 Cheng YJ, Gregg EW, Geiss LS, Imperatore G, et al. Association of A1C and fasting plasma glucose levels with diabetic retinopathy prevalence in the US population: implications for diabetes diagnostic thresholds. Diabetes Care 2009; 32: 2027–2032.
- 52 Khaw KT, Wareham N, Luben R, et al. Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospective investigation of cancer and nutrition (EPIC-Norfolk). BMJ 2001; 322: 15–18.
- 53 Saito T, Watanabe M, Nishida J. Lifestyle modification and prevention of type 2 diabetes in overweight Japanese with impaired fasting glucose levels: a randomized controlled trial. Arch Intern Med 2011; 171: 1352–1360.
- 54 Herranz L, Saez-de-Ibarra L, Grande C, Pallardo LF. Non-glycemic-dependent reduction of late pregnancy A1C levels in women with type 1 diabetes. Diabetes Care 2007; 30: 1579–1580.
- 55 Coban E, Ozdogan M, Timuragaoglu A. Effect of iron deficiency anemia on the levels of hemoglobin A1c in nondiabetic patients. Acta Haematol 2004; 112: 126–128.
- 56 Tarim O, Kucukerdogan A, Gunay U, Eralp O, Ercan I. Effects of iron deficiency anemia on hemoglobin A1c in type 1 diabetes mellitus. Pediatr Int 1999; 41: 357–362.
- 57 Hashimoto K, Noguchi S, Morimoto Y, et al. A1C but not serum glycated albumin is elevated in late pregnancy owing to iron deficiency. Diabetes Care 2008; 31: 1945–1948.
- 58 Camargo JL, Stifft J, Gross JL. The effect of aspirin and vitamins C and E on HbA1c assays. Clin Chim Acta 2006; 372: 206–209.
- 59 Proto G, De Marchi S, Cecchin E. Glycosylated hemoglobin in chronic alcoholics. Drug Alcohol Depend 1983; 12: 299–302.
- 60 Higgins T, Saw S, Sikaris K, et al. Seasonal variation in hemoglobin A1c: is it the same in both hemispheres? J Diabetes Sci Technol 2009; 3: 668–671.
- 61 Herman WH, Ma Y, Uwaifo G, et al. Differences in A1C by race and ethnicity among patients with impaired glucose tolerance in the Diabetes Prevention Program. Diabetes Care 2007; 30: 2453–2457.
- 62 Pani LN, Korenda L, Meigs JB, et al. Effect of aging on A1C levels in individuals without diabetes: evidence from the Framingham Offspring Study and the National Health and Nutrition Examination Survey 2001–2004. Diabetes Care 2008; 31: 1991–1996.
- 63 Ng JM, Jennings PE, Laboi P, Jayagopal V. Erythropoetin treatment significantly alters measured glycated haemoglobin (HbA1c). Diabet Med 2008; 25: 239–240.
- 64 Gram-Hansen P, Eriksen J, Mourits-Andersen T, Olesen L. Glycosylated haemoglobin (HbA1c) in iron- and vitamin B12 deficiency. J Intern Med 1990; 227: 133–136.
- 65 Willekens FL, Roerdinkholder-Stoelwinder B, Groenen-Dopp YA, et al. Hemoglobin loss from erythrocytes in vivo results from spleen-facilitated vesiculation. Blood 2003; 101: 747–751.
- 66 Schnedl WJ, Wallner SJ, Piswanger C, Krause R, Lipp RW. Glycated hemoglobin and liver disease in diabetes mellitus. Wien Med Wochenschr 2005; 155: 411–415.
- 67 Albright ES, Ovalle F, Bell DS. Artificially low hemoglobin A1c caused by use of dapsone. Endocr Pract 2002; 8: 370–372.
- 68 Diop ME, Bastard JP, Meunier N, et al. Inappropriately low glycated hemoglobin values and hemolysis in HIV-infected patients. AIDS Res Hum Retroviruses 2006; 22: 1242–1247.
- 69 Robertson M. Artificially low HbA1c associated with treatment with ribavirin. BMJ 2008; 336: 505.
- 70 Bernstein RM, Freedman DB, Liyanage SP, Dandona P. Glycosylated haemoglobin in rheumatoid arthritis. Ann Rheum Dis 1982; 41: 604–606.
- 71 Gunton JE, McElduff A. Hemoglobinopathies and HbA(1c) measurement. Diabetes Care 2000; 23: 1197–1198.
- 72 Rubinow KB, Hirsch IB. Reexamining metrics for glucose control. JAMA 2011; 305: 1132–1133.
- 73 Cohen RM, Snieder H, Lindsell CJ, et al. Evidence for independent heritability of the glycation gap (glycosylation gap) fraction of HbA1c in nondiabetic twins. Diabetes Care 2006; 29: 1739–1743.
- 74 Ferrannini E, Nannipieri M, Williams K, Gonzales C, Haffner SM, Stern MP. Mode of onset of type 2 diabetes from normal or impaired glucose tolerance. Diabetes 2004; 53: 160–165.
- 75 Tabak AG, Jokela M, Akbaraly TN, Brunner EJ, Kivimaki M, Witte DR. 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.
- 76 Mason CC, Hanson RL, Knowler WC. Progression to type 2 diabetes characterized by moderate then rapid glucose increases. Diabetes 2007; 56: 2054–2061.
- 77 Heianza Y, Arase Y, Fujihara K, et al. Longitudinal trajectories of HbA1c and fasting plasma glucose levels during the development of type 2 diabetes: the Toranomon Hospital Health Management Center Study 7 (TOPICS 7). Diabetes Care 2012; 35: 1050–1052.
- 78 Sabanayagam C, Liew G, Tai ES, et al. Relationship between glycated haemoglobin and microvascular complications: is there a natural cut-off point for the diagnosis of diabetes? Diabetologia 2009; 52: 1279–1289.
- 79 Wong TY, Liew G, Tapp RJ, et al. Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies. Lancet 2008; 371: 736–743.
- 80 Bergman M. Inadequacies of absolute threshold levels for diagnosing prediabetes. Diabetes Metab Res Rev 2010; 26: 3–6.
- 81 Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393–403.
- 82 Roth J, Whitford I, Dankner R, Szulc AL. How the immunoassay transformed C-peptide from a duckling into a swan. Diabetologia 2012; 55: 865–869.
- 83 Johnson JL, Duick DS, Chui MA, Aldasouqi SA. Identifying prediabetes using fasting insulin levels. Endocr Pract 2010; 16: 47–52.
- 84 Dankner R, Shanik MH, Keinan-Boker L, Cohen C, Chetrit A. Effect of elevated basal insulin on cancer incidence, and on mortality in cancer incident patients: the Israel Glucose Intolerance, Obesity and Hypertension (GOH) 29-year follow-up study. Diabetes Care 2012; 35: 1538–1543.
- 85 Warram JH, Martin BC, Krolewski AS, Soeldner JS, Kahn CR. Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Ann Intern Med 1990; 113: 909–915.
- 86 Weyer C, Hanson RL, Tataranni PA, Bogardus C, Pratley RE. A high fasting plasma insulin concentration predicts type 2 diabetes independent of insulin resistance: evidence for a pathogenic role of relative hyperinsulinemia. Diabetes 2000; 49: 2094–2101.
- 87 Rahbar S, Blumenfeld O, Ranney HM. Studies of an unusual hemoglobin in patients with diabetes mellitus. Biochem Biophys Res Commun 1969; 36: 838–843.
- 88 Rahbar S. The discovery of glycated hemoglobin: a major event in the study of nonenzymatic chemistry in biological systems. Ann N Y Acad Sci 2005; 1043: 9–19.
- 89 National Glycohemoglobin Standardization Program (2012). Factors that interfere with HbA1c test results. Available from http://www.ngsp.org/factors.asp
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