Insulin secretion and insulin sensitivity in relation to glucose tolerance: lessons from the Botnia Study.

Abstract

Recently, a new stage in glucose tolerance, impaired fasting glucose (IFG) (fasting plasma glucose level of 6.1-6.9 mmol/l), was introduced in addition to impaired glucose tolerance (IGT) (2-h glucose level of 7.8-11.0 mmol/l). It is not clear whether IFG and IGT differ with respect to insulin secretion or sensitivity. To address this question, we estimated insulin secretion (by measuring both insulin levels and the ratio of insulin-toglucose levels in 30-min intervals) and insulin sensitivity (by using the homeostasis model assessment 1.73 ± 0.03, P < 0.0005), had greater insulin responses during an OGTT (P = 0.0001), had higher waist-to-hip ratios (P < 0.005), had higher triglyceride and total cholesterol concentrations (P < 0.0005), and had lower HDL cholesterol concentrations (P = 0.0001). Compared with subjects with IFG, subjects with IGT had a lower incremental 30-min insulin-to-glucose area during an OGTT (13.8 ± 1.7 vs. 21.7 ± 1.7, P = 0.0008). Compared with subjects with IGT, subjects with mild diabetes (fasting plasma glucose levels <7.8 mmol/l) showed markedly impaired insulin secretion that could no longer compensate for IR and elevated glucose levels. A progressive decline in insulin sensitivity was observed when moving from NGT to IGT and to subjects with diabetes (P < 0.05 for trend), whereas insulin secretion followed an inverted U-shaped form. We conclude that IFG is characterized by basal IR and other features of the metabolic syndrome, whereas subjects with IGT have impaired insulin secretion in relation to glucose concentrations. An absolute decompensation of ␤-cell function characterizes the transition from IGT to mild diabetes. Diabetes 49:975-980, 2000

Different contributions of insulin resistance and beta‐cell dysfunction in overweight Israeli Arabs with IFG and IGT

“…Our results are consistent with other studies performed in other populations, which found that an increase in insulin resistance is the principal defect observed in subjects with IFG, while impairment in beta-cell function is the major pathology that leads to the development of IGT [8][9][10][11]. However, some other studies found opposite results [12][13][14].…”

“…Interestingly, subjects with isolated IFG and combined glucose tolerance (CGT) manifested higher frequency of lipid disturbances, which are associated with increased insulin resistance [24], and therefore had a higher frequency of the metabolic syndrome compared to subjects with NGT and IGT. Normal subjects in this population had normal fasting and 2-h glucose concentrations and their HOMA-IR values were relatively greater than NGT subjects in other populations [10,12]. Higher BMI (31 in this study compared to [25][26][27] in the other studies) may explain the large HOMA-IR value in this population.…”

“…Studies that aimed to clarify this question had conflicting results. Some studies reported an increase in insulin resistance as the main contributor to the development of IFG, while IGT was associated with impairment of betacell function [8][9][10][11]. Other studies demonstrated that subjects with IFG had mainly a reduction in insulin secretion, while IGT subjects had a reduction in insulin sensitivity [12][13][14].…”

Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study

“…In a study of Pima Indians, participants with isolated IFG and isolated IGT showed similar impairments in insulin sensitivity, but those with isolated IFG had a more pronounced defect in early insulin release and higher endogenous glucose output [10]. Tripathy et al [11], on the other hand, concluded that IFG was characterised by insulin resistance, whereas persons with IGT had impaired insulin secretion. Similar findings were reported by Hanefeld et al [15].…”

“…Previous studies have given conflicting data on the association of IFG and IGT with insulin resistance and impaired insulin secretion [10][11][12][13][14][15][16][17][18][19][20]. In a study of Pima Indians, participants with isolated IFG and isolated IGT showed similar impairments in insulin sensitivity, but those with isolated IFG had a more pronounced defect in early insulin release and higher endogenous glucose output [10].…”