Glycated haemoglobin predicts progression to diabetes mellitus in Pima Indians with impaired glucose tolerance

Abstract

Summary Glycated haemoglobin could offer several practical advantages over the OGTT for assessing glucose metabolism. Initial cross-sectional studies (1983)(1984)(1985) on 381 subjects (mostly Pima Indians) described the relationship between HbAlc (a specific glycated Hb) and the OGTT. We performed follow-up OGTTs and HbA~c measurements on 257 of these same subjects 1.6-6.1 years later. Subjects were again grouped according to both the result of the OGTT (normal, IGT or diabetes, by WHO criteria) and HbA~ result (normal or elevated based on mean + 1.96 SD of normal). Of 66 subjects with IGT at baseline, 47 (71%) had normal HbAlo and 19 (29 % ) had elevated HbAlo. Twentysix (39 %) of these subjects had diabetes at follow-up. Of these subjects with IGT, a significantly greater percentage of subjects with elevated HbAlc at baseline (68 %) showed worsening to diabetes than those with a normal HbAlo (28%); (chi-square =7.8, dr= 1, p < 0.01). Thus, in subjects with IGT, glycated Hb may be a useful predictor of progression to diabetes. [Diabetologia (1994) 37: 252-256] Key words Follow-up study, glycated Hb, HbA~ c, IGT, Pima Indians.The OGTT is often used to diagnose diabetes mellitus as well as to detect more mildly impaired carbohydrate metabolism. Measurement of glycated Hb has been suggested as an alternative to the OGTT for assessing glucose metabolism [1][2][3][4]. The concentration of glycated Hb is increased within erythrocytes of patients in proportion to the degree of chronic hyperglycaemia; it is an indirect measure of the average blood glucose concentration over the previous 2 to 3 months [3]. Glycated Hb is widely used for monitoring long-term glycaemic control in known diabetic patients [5][6][7][8], and the prognostic value of glycated Hb has been investigated in a longitudinal study design of patients with normal glucose tolerance [9]. Measurement of glycated Hb offers some practical advantages over the OGTT; it is not influenced by time of day, recent activity levels, metabolic stress, or food intake [7]. Only minimal patient cooperation is required before and during the test, and only one small blood sample is required.Our initial cross-sectional studies [4] described the relationship between HbAlc, a specific glycated Hb, and OGTT. In 381 subjects (mostly Pima Indians) from a population with a high prevalence of non-insulin-dependent diabetes mellitus, HbA~c had high specificity and moderate sensitivity as a screening test for diabetes defined by the OGTT using WHO criteria [4]. Here we re-examine these same individuals 1 to 6 years later to investigate the prognostic value of glycated Hb. By using both OGTT and glycated Hb results, we attempted to identify, among a group of high risk subjects, those who are at greatest risk of developing diabetes.

Estimation of the contribution of biomarkers of different metabolic pathways to risk of type 2 diabetes

“…Previous studies have shown that circulating HbA1c levels are associated with the conversion of pre-diabetic phase into clinical diabetes [35][36][37][38]. Further, a strong association between baseline HbA1c and incidence of type 2 diabetes was also suggested in a large-scale prospective study among middle aged women [39].…”

Determinants of progression from impaired fasting glucose and impaired glucose tolerance to diabetes in a high-risk screened population: 3 year follow-up in the ADDITION study, Denmark

“…Progression rates for isolated IGT were similar to those for isolated IFG and progression rates for the combined IFG and IGT group were higher in each observation period. Fewer determinants of progression were identified in the IGT group than in population-based studies, where most consistently the following were identified: higher levels of blood glucose (HbA 1c , FBG, 2hBG), obesity (BMI and WHR), known hypertension and ethnicity [12,13,15]. However, the Hoorn study only found 2hBG and fasting proinsulin to be predictors of progression [14].…”

“…By knowing which risk factors or changes in risk factor levels determine progression to diabetes, we may be able to develop individualised focused interventions. Current publications on determinants of progression from IGT have studied population-based cohorts including moderate and low-risk individuals; few studies have reported on IFG [10][11][12][13][14][15][16].…”

Non-pharmacological interventions to reduce the risk of diabetes in people with impaired glucose regulation: a systematic review and economic evaluation.

“…BMI was 29.5 kg/m 2 . 42 In a study by Little et al (1994) 45 in Pima Indians, 39% progressed from IGT to diabetes after a mean follow-up of 3.3 years, but the proportion developing diabetes was much higher in those with a raised baseline HbA 1c level (13 out of 19; 68%) than in those with a normal baseline HbA 1c level (13 out of 47; 28%). The upper limit of normal HbA 1c level was taken to be 6%.…”