Abstract
In order to identify early abnormalities in non-insulin-dependent diabetes mellitus (NIDDM) we determined insulin (using an assay that does not cross-react with proinsulin) and proinsulin concentrations. The proinsulin/insulin ratio was used as an indicator of abnormal beta-cell function. The ratio of the first 30-min increase in insulin to glucose concentrations following the oral glucose tolerance test (OGTT; I30-0/G30-0) was taken as an indicator of insulin secretion. Insulin resistance (R) was evaluated by the homeostasis model assessment (HOMA) method. True insulin and proinsulin were measured during a 75-g OGTT in 35 individuals: 20 with normal glucose tolerance (NGT) and without diabetes among their first-degree relatives (FDR) served as controls, and 15 with NGT who were FDR of patients with NIDDM. The FDR group presented higher insulin (414 pmol/l vs 195 pmol/l; P = 0.04) and proinsulin levels (19.6 pmol/l vs 12.3 pmol/l; P = 0.03) post-glucose load than the control group. When these groups were stratified according to BMI, the obese FDR (N = 8) showed higher fasting and post-glucose insulin levels than the obese NGT (N = 9) (fasting: 64.8 pmol/l vs 7.8 pmol/l: P = 0.04, and 60 min post-glucose: 480.6 pmol/l vs 192 pmol/l: P = 0.01). Also, values for HOMA (R) were higher in the obese FDR compared to obese NGT (2.53 vs 0.30; P = 0.075). These results show that FDR of NIDDM patients have true hyperinsulinemia (which is not a consequence of cross-reactivity with proinsulin) and hyperproinsulinemia and no dysfunction of a qualitative nature in beta-cells.
Highlights
Non-insulin-dependent diabetes mellitus (NIDDM) is a heterogeneous disorder characterized by insulin resistance, decreased insulin secretion and increased hepatic glucose production
These results show that first-degree relatives (FDR) of non-insulin-dependent diabetes mellitus (NIDDM) patients have true hyperinsulinemia and hyperproinsulinemia and no dysfunction of a qualitative nature in ß-cells
First-degree relatives of NIDDM patients had a higher prevalence of impaired glucose tolerance (IGT) or NIDDM diagnosed by the oral glucose tolerance test (OGTT) compared to the control group (12/27 vs 1/21; P = 0.02)
Summary
Non-insulin-dependent diabetes mellitus (NIDDM) is a heterogeneous disorder characterized by insulin resistance, decreased insulin secretion and increased hepatic glucose production. The role of these abnormalities as the earliest or primary causative factors of NIDDM is controversial. Studies on individuals at high risk to develop the disease, such as offspring of patients with NIDDM and certain population groups, have provided important information. In the present study we determined concentrations of proinsulin and insulin (using an assay that does not cross-react with proinsulin) in response to an oral glucose load in individuals with normal glucose tolerance (NGT) who were relatives of NIDDM patients and in control individuals with no family history of diabetes mellitus
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