Heterogeneous relationship of early insulin response and fasting insulin level with development of non-insulin-dependent diabetes mellitus in non-diabetic Japanese subjects with or without obesity
Introduction
The question of whether insulin deficiency or insulin resistance is a primary precursor of non-insulin-dependent diabetes mellitus (NIDDM) remains controversial. Studies have variously revealed that insulin secretory dysfunction [1], [2], [3], [4], [5], [6], [7], increased insulin resistance [8], [9], [10], [11], [12], [13], [14], [15], [16], or a combination of both factors may initiate the development of NIDDM [17], [18], [19], [20], [21], [22], [23]. Most of the populations in which insulin resistance is considered to be the primary pathogenic cause of diabetes have a higher degree of obesity [8], [9], [10], [11], [12], [13], [14], [15], [16] than those with primary insulin secretory dysfunction [1], [3], [4]. Thus, we thought that the degree of obesity might be one of the reasons for this discrepancy [24]. In order to test this possibility, we performed a prospective study to investigate the association of insulin secretion and insulin resistance with the progression of diabetes in non-obese and obese subjects.
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Subjects and methods
The subjects, most of them government officials and their spouses, were selected from the persons participating in a general health check-up in Toranomon Hospital. A screening for diabetes mellitus was included in this general examination. Subjects with HbA1c≥6.2%, or fasting blood glucose ≥100 mg/dl (capillary whole blood), or positive urine sugar were recommended to receive a 100 g oral glucose tolerance test (OGTT). Between 1986 and 1994, 1604 subjects (1285 men and 319 women) followed for
Results
Among the 1604 subjects followed-up, 129 developed diabetes mellitus. Baseline characteristics of the subjects who developed and those who did not develop NIDDM are shown in Table 1. In the whole group (non-obese and obese), those who developed diabetes had more males, more positive family history of diabetes, higher BMI, higher blood glucose (fasting and 2-h), fasting insulin levels and HOMA-R, and lower insulinogenic index. In both non-obese and obese subjects, those who developed diabetes
Discussion
Hyperglycemia is known to be a strong predictor of diabetes. Our present study showed the same results. In this study, we investigated whether fasting insulin level and insulinogenic index were independent predictors of NIDDM when fasting blood glucose and 2-h blood glucose were taken into account. Under these conditions, insulinogenic index proved to be a significant predictor of diabetes in the non-obese group, and in the whole group. Insulinogenic index (ratio of increment of insulin to that
Acknowledgements
This study was supported by a Grant for Diabetes Research from the Ministry of Health and Welfare of Japan.
References (38)
- et al.
Sequential changes in serum insulin concentration during development of non-insulin-dependent diabetes
Lancet
(1989) - et al.
Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study
Lancet
(1992) Diagnostic criteria for diabetes mellitus in Japan—from a report of the Japan Diabetes Society (JDS) Committee on the Diagnosis of Diabetes Mellitus, 1982
Diabetes Res. Clin. Pract.
(1994)- et al.
A simple measure of insulin resistance
Lancet
(1995) - et al.
FIRI: a fair insulin resistance index?
Lancet
(1996) - et al.
Efficacy of troglitazone measured by insulin resistance index
Lancet
(1997) - et al.
Decreased sensitivity of the pancreatic beta cells to glucose in prediabetic and diabetic subjects. A glucose dose–response study
Diabetes
(1972) - et al.
Insulin responses in equivocal and definite diabetes, with special reference to subjects who had mild glucose intolerance but later developed definite diabetes
Diabetes
(1977) - et al.
Risk factors for worsening to diabetes in subjects with impaired glucose tolerance
Diabetologia
(1984) - et al.
Beta-cell dysfunction, rather than insulin insensitivity, is the primary defect in familial type 2 diabetes
Lancet
(1986)
Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance
New Engl. J. Med.
The pathogenesis of NIDDM
Diabetologia
The l3-cell in diabetes: from molecular genetics to clinical research
Diabetes
Hyperinsulinemia in a population at high risk for non-insulin-dependent diabetes mellitus
New Engl. J. Med.
Plasma insulin response among Nauruans: prediction of deterioration in glucose tolerance over 6 yr
Diabetes
Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents
Ann. Intern. Med.
The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican–American NIDDM parents
Diabetes
Hyperinsulinaemia in youth is a predictor of type 2 (non-insulin-dependent) diabetes mellitus
Diabetologia
Insulinemia in children at low and high risk of NIDDM
Diabetes Care
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