Treatment of prediabetes

Abstract

Progression of normal glucose tolerance (NGT) to overt diabetes is mediated by a transition state called impaired glucose tolerance (IGT). Beta cell dysfunction and insulin resistance are the main defects in type 2 diabetes mellitus (type 2 DM) and even normoglycemic IGT patients manifest these defects. Beta cell dysfunction and insulin resistance also contribute to the progression of IGT to type 2 DM. Improving insulin sensitivity and/or preserving functions of beta-cells can be a rational way to normalize the GT and to control transition of IGT to type 2 DM. Loosing weight, for example, improves whole body insulin sensitivity and preserves beta-cell function and its inhibitory effect on progression of IGT to type 2 DM had been proven. But interventions aiming weight loss usually not applicable in real life. Pharmacotherapy is another option to gain better insulin sensitivity and to maintain beta-cell function. In this review, two potential treatment options (lifestyle modification and pharmacologic agents) that limits the IGT-type 2 DM conversion in prediabetic subjects are discussed.

Keywords: Diabetes prevention; Impaired fasting glucose; Impared glucose tolerance; Prediabetes; Type 2 diabetes mellitus.

Figure 1

Natural history of type 2 diabetes mellitus. The plasma insulin response (open circles) depicts the classic Starling’s curve of the pancreas. Closed circles = insulin-mediated glucose uptake (top panel). DIAB: Diabetes; Hi INS: High insulin secretion; IGT: Impaired glucose tolerance; Lo INS: Low insulin secretion; NGT: Normal glucose tolerance; OB: Obese; OGTT: Oral glucose tolerance test.

Figure 2

Insulin secretion/insulin resistance (disposition) index (defined as change in insulin/change in glucose/insulin resistance) in individuals with normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes mellitus as a function of the 2-h plasma glucose concentration in lean (closed circles) and obese (open circles) subjects. IGT: Impaired glucose tolerance; NGT: Normal glucose tolerance; T2DM: Type 2 diabetes mellitus; PG: Plasma glucose; ΔINS/ΔGLU/IR: Change in insulin/change in glucose ÷ insulin resistance.

Figure 3

Plasma glucose concentration during the oral glucose tolerance test in normal glucose tolerant (close circles) individuals and in subjects with impaired glucose tolerance (closed triangles) and impaired fasting glucose (open circles).

Figure 4

Incidence of diabetes during follow-up, according to the success score. At the one-year visit, each subject received grade of 0 for each intervention goal that had not been achieved and a grade 1 for each goal that had been achieved; the success score was computed as the sum of the grades (reproduced from J Tuomilehto and J Lindström).

Figure 5

Change in body weight during the dipeptidyl peptidase, during the overlap period, and during the Dipeptidyl peptidase Outcomes Study (reproduced from Eriksson and Lindgärde). DPP: Dipeptidyl peptidase; DPPOS: Dipeptidyl peptidase Outcomes Study.

Figure 6

Effect of lifestyle intervention, metformin, and troglitazone on the conversion rate of ımpaired glucose tolerance to type 2 diabetes in the first 1.5 years of the dipeptidyl peptidase (i.e, before the discontinuation of troglitazone from the dipeptidyl peptidase). ^bP < 0.01 vs LS-light, ^dP < 0.01 vs LS-heavy. LS: Lifestyle; MET: Metformin; TROG: Troglitazone.

Figure 7

Effect of physiologic (A) and pharmacologic (B) doses of glucagon-like peptide-1 on insulin secretion in normal glucose tolerance individuals and in subjects with type 2 diabetes mellitus. GLP-1: Glucagon-like peptide-1.