Glucose Tolerance and Insulin Response to Glucose in Two Large Families with Diabetic Mothers in the First Generation

Abstract

The intravenous glucose tolerance and insulin response to glucose infusion was studied in two large families with diabetic mothers in the first generation, 42 family members in all. Manifest diabetes occurred in only one subject who belonged to generation 11, while decreased glucose tolerance was much more common. Delayed and decreased initial insulin response to glucose was observed in the majority of the family members including thosc with normal glucose tolerance. The frequency of low insulin response diminished with each generation. These findings, together with previous ones on healthy monozygotic twin sibs of diabetic patients, indicate that a decreased initial insulin response to glucose may be an inherited and predisposing factor in diabetes mellitus. The present material is insufficient to aHow any conclusions regarding the inheritance of this factor. However, it emphasizes the necessity of studying the pattern of insulin secretion when investigating the mode of inheritance of.diabetes.

Pathogenesis of type 2 diabetes mellitus

“…The concept that impaired insulin secretion was the primary pathogenic factor in type 2 diabetes mellitus was first proposed in 1967 by Cerasi and Luft based on their findings that insulin secretion was under genetic control (Iselius et al, 1985), and that it was reduced in normal glucose-tolerant individuals who have a first-degree relative with type 2 diabetes mellitus (Cerasi and Luft, 1967). This latter finding has been confirmed in 15 subsequent studies (Lemieux et al, 1992;Simpson et al, 1968;Boden et al, 1968;Daweke et al, 1968;Martin et al, 1992;Rojas et al, 1969;Serrano-Rias et al, 1970;Rull et al, 1970;Pozefsky et al, 1973;Boberg et al, 1976;Ohlsen et al, 1971;Berntorp and Lindgarde, 1985;O'Rahilly et al, 1988;Cerasi and Luft, 1963;Fernandez-Castaner et al, 1996;Schmitz et al, 1997;Pimenta et al, 1995), the more recent utilizing the hyperglycemic clamp ( Fig. 1) and/or minimal model techniques.…”

Factors Predicting the Course of Diabetes Mellitus in Hyperthyroid Patients

“…It has been reported that the initial insulin response to glucose infusion was reduced or absent in diabetes mellitus (Cerasi and Luft 1967a). Since hyperthyroidism itself does not decrease insulin secretion in response to glucose loading (Anderson, Friis and Ottesen 1977;Wajchenberg, Cesar, Leme, Souza, Pieroni andMatter l978;Hamada,Ito, Mimura,Momotani, Nishikawa, Ban, Fujii, Morii and Wada 1979), and since insulin response to glucose load is considered to be genetically regulated (Cerasi and Luft 1967b;Ohlsen, Cerasi and Luft 1971), a predisposition to diabetes may be an important factor in permanent diabetes in patients with hyperthyroidism. The T 3 and T 4 levels in the hyperthyroid state did not correlate with the later persistence of diabetes, but the duration of hyperthyroidism seemed to have an influence, so it is possible that the length rather than the intensity of the stress is more influential.…”

A la recherche du temps perdu — epilogue to the Minkowski award lecture 1974

“…Our assumption, however, has been that in Type 2 diabetes, where the genetic component is dominant, the low insulin response is an inherited trait. This assumption was based on the following observations: (1) In monozygot-~c non-diabetic twins of diabetic patients, and in two families with Type 2 diabetes in several generations, the incidence of a low insulin response to glucose was very high [21,22]. (2) In children aged 7-16 years the distribution of the insulin response to glucose was similar to that found in adults, about 20% of children showing a low insulin response [23].…”