The inheritance of essential diabetes mellitus from studies of the synalbumin insulin antagonist

Abstract

Summary. Patients with essential diabetes including prediabetes have more synalbumin antagonism to insulin than normal subjects or patients with "pancreatic" diabetes, e.g. after panereatectomy. Thus excessive synalburain antagonism (synalbumin positive) can be regarded as a biochemical marker to ascertain whether a given person is constituted as an essential diabetic --without reference to carbohydrate intolerance. --On this premise, the genetic transmission of essential diabetes has been examined by studying the relatives of essential diabetics. The results strongly suggest that excessive synalbumin antagonism is inherited as an autosomal "dominant" character. --Ninety-seven members of nine families were studied, 39 were synalbumin negative whereas 58 were synalbumin positive, but only 16 of these latter have overt carbohydrate intolerance. A further three have spontaneous hypoglycaemia whereas the remainder are quite asymptomatic. These observations suggest that overt carbohydrate intolerance is relatively uncommon or will be a late event in many people constituted as essential diabetics.L'hdrdditd du diab~te sucr5 essentiel d'apr@s des gtudes de l'antagoniste synalbuminique de l'insuline.Rgsumg. Les patients atteints de diab@te essentiel, y compris les pr6diab6tiques, ont davantage d'antagonisme synalbuminique vis-a-vis de l'insuline que les sujets normaux ou les patients atteints de diab~te ((pancr@atique)) c-~-d, apr@s pancr6atectomie. L'antagonisme synalbuminiclue excessif (synalbumine positif) peut done @tre consid6r6 comme un crit~re biochimique pour d6terminer si une personne donnde a une constitution de diab6tique essentiel --sans se r6f6rer ~ l'intol6rance aux hydrates de carbone. --A partir de ceci, la transmission g6ndtique du diab~te essentiel a 6t6 examin6e par l'dtude des parents des diab6tiques essentiels. Les r6sultats sugg~rent fortement que l'antagonisme synalbuminique excessif se transmet comme un caract~re autosomial ((dominant)~. --Quatre-vingt-dix-sept membres appartenant ~ neuf faraffles ont gt6 6tudi6s, 39 gtaient synalbumine nggatif, tandis que 58 gtaient synalbumine positif, mais seulement 16 de ces derniers avaient une intolgrance manifeste aux hydrates de carbone. Trois autres avaient une hypoglyc6mie spontan6e, tandis que les autres 6talent compl@te-ment asymptomatiques. Ces observations sugg@rent que l'intolgrance manifeste aux hydrates de earbone est relativement peu fr6quente, ou qu'elle sera un 6v~nement tardif chez beaucoup de personnes ayant la constitution de diab6tiques essentiels. It has long been reeognised that there is a higher incidence of diabetes mellitus among the relatives of diabetics than among the rest of the population. Nevertheless, there is apparently considerable confusion regarding the mode of inheritance of this condition. After reviewing much of the available evidence ~:)I~CUs and WHITE [7] and STEI~E~O [8,9] conclude that predisposition to diabetes is probably due to homozygosis for a recessive gene; although a number of investigators hold different vie...

Assay of Insulin Antagonism by Serial Incubation of Paired Rat Hemidiaphragms

“…Although the albumin-associated antagonist has proven difficult to study for the reasons discussed above, the gross difference in levels between diabetics and normal controls and the demonstration of increased levels in prediabetics 33 suggest that further work with this antagonist may be rewarding. Since large amounts of endogenous insulin are incorporated into the albumin fractions prepared by the TCA-ethanol (acid alcohol) extraction, 25 -34 human fraction V has been chosen for subsequent studies on the mechanism of insulin antagonism by albumin.…”

Pancreatic Disorders and Diabetes Mellitus-A Review

“…The most likely explanation is that there is an inherited liability to develop diabetes mellitus which is distinct from the factors which precipitate its onset and determine its type. Vallanceowen & Ashton 10 have found that 50% of relatives of diabetes are synalbumin positive, whereas 20% of controls are synalbumin positive. They find that all patients with idiopathic diabetes are synalbumin positive, whether of juvenile or adult onset type.…”

Insulin-like Activity

“…12 Although this synalbumin factor is present in normal plasma, its antagonistic activity is masked by the production of adequate amounts of insulin. Hence, albumin concentrations of 3.5 to 5.5 per cent are found to inhibit the action of 1,000 /*U. insulin added in vitro in both normal and diabetic sera, 134 but with lower concentrations of albumin (1.25 per cent) the inhibitory activity disappears from normal serum, although it is still strongly positive in diabetic serum. It is also positive at this concentration in sera of obese diabetics and prediabetics 134 and excessive circulating synalbumin levels are reported in relatives of diabetics 135 - 136 and in those having conditions more prevalent in the diabetic state such as myocardial infarction.…”

“…Hence, albumin concentrations of 3.5 to 5.5 per cent are found to inhibit the action of 1,000 /*U. insulin added in vitro in both normal and diabetic sera, 134 but with lower concentrations of albumin (1.25 per cent) the inhibitory activity disappears from normal serum, although it is still strongly positive in diabetic serum. It is also positive at this concentration in sera of obese diabetics and prediabetics 134 and excessive circulating synalbumin levels are reported in relatives of diabetics 135 - 136 and in those having conditions more prevalent in the diabetic state such as myocardial infarction. 137 Synalbumin antagonism is said to be inherited as a Mendelian dominant characteristic, thus being a diabetic "marker" 135 ' 136 and no antagonism is detected in sera of diabetics secondary to pancreatectomy or hemochromatosis.…”