The definition of chemical diabetes

The natural history of diabetes mellitus can be arbitrarily divided into four stages based on the presence or absence of abnormal carbohydrate metabolism. Overt diabetes is the most advanced stage, characterized by elevated fasting blood glucose concentration and classical symptoms. This stage is divided into ketotic and nonketotic forms. Preceding overt diabetes is the latent or chemical diabetic stage, with no symptoms of diabetes but demonstrable abnormality of oral or intravenous glucose tolerance. Subclinical diabetes is an earlier stage when glucose tolerance is abnormal only with stress, such as pregnancy or the administration of cortisone. The earliest stage, prediabetes, extends from conception until the first demonstrable abnormality in glucose tolerance. In groups of presumed prediabetic individuals, delayed and/or decreased plasma insulin response to glucose has been noted. Progression of the diabetes may not occur, may occur very slowly or very rapidly, and regression to an earlier stage of abnormality may also occur.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33955/1/0000225.pd

Treatment of chemical diabetes mellitus with sulfonylurea compounds

Abnormality in glucose tolerance appears to correlate with arteriosclerotic disease, even when the abnormality is quite mild. Though there is no evidence for prevention of these vascular problems by correction of the carbohydrate abnormality, it seems reasonable to attempt such a correction in an investigational setting. We have used sulfonylurea (tolbutamide, chlorpropamide) in children and young adults (9-35 yr) without obesity, who have chemical diabetes. No apparent effect on insulin output has been noted, even with normalization of glucose tolerance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33962/1/0000232.pd

METABOLIC STUDIES OF CHLORPROPAMIDE IN NORMAL MEN AND IN DIABETIC SUBJECTS

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72472/1/j.1749-6632.1959.tb39585.x.pd

Stimulation by prostaglandin E2 of glucagon and insulin release from isolated rat pancreas

To ascertain whether prostaglandins (PG) may play a role in the secretion of glucagon and in an attempt to elucidate the conflicting observations on the effects of PG on insulin release, the isolated intact rat pancreas was perfused with solutions containing 1.1 x 10-9 to 1.8 x 10-5M PGE2. In the presence of 5.6 mM glucose significant increments in portal venous effluent levels of glucagon and insulin were observed in response to minimal concentrations of 2.8 x 10-8 and 1.4 x 10-7M PGE2, respectively; a dose-response relationship was evident for both hormones at higher concentrations of PGE2. When administered over 60 seconds, 1.4-10-6M PGE2 resulted in a significant increase in glucagon levels within 24 seconds and in insulin within 48 seconds. Ten-minute perfusions of 1.4 x 10-6M PGE2 elicited biphasic release of both islet hormones; Phase I glucagon release preceded that of insulin. Both phases of the biphasic glucagon and insulin release which occurred in response to 15-minute perfusions of 10 mM arginine were augmented by PGE2. These observations indicate that PGE2 can evoke glucagon and insulin release at concentrations close to those observed by others in the extracts of rat pancreas. We conclude that PG may be involved in the regulation of secretion of glucagon and insulin and may mediate and/or modify the pancreatic islet hormone response to other secretagogues.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21999/1/0000412.pd

Studies on the natural history of asymptomatic diabetes in young people

Forty-five young patients with chemical diabetes have been followed for 1-16 yr. Among 21 of them aged 9-17 yr, 4 have developed insulin-dependent diabetes mellitus. None of the 24 aged 18-25 yr have decompensated. Delayed and subnormal insulin response to oral glucose was noted in those with chemical diabetes compared to normals, except for one nonobese patient who had hyperinsulinemia. Considerable fluctuation in glucose and/or insulin responses and their relationship was noted in repeated testing. These observations emphasize that validation of diagnostic criteria for glucose tolerance test interpretation need not depend on a high rate of progression to more severe hyperglycemia, and that the slow progression of latent diabetes permits consideration of prophylactic measures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33960/1/0000230.pd

Maturity-onset diabetes of the young

Maturity-onset diabetes of the young (MODY) is a subtype of noninsulin dependent diabetes mellitus (NIDDM). It is characterized by an early age of onset and autosomal dominant mode of inheritance. These features and the availability of large multigenerational pedigrees make MODY useful for genetic studies of diabetes. In the large, 5-generational RW pedigree, MODY is tightly linked to genetic markers on chromosome 20q. Affected subjects in this family show abnormalities of carbohydrate metabolism varying from impaired glucose tolerance (IGT) to severe diabetes. Approximately 30% of diabetic subjects become insulin requiring and vascular complications occur. MODY is also linked to the glucokinase gene on chromosome 7p and many different mutations associated with MODY have been identified in this gene. MODY due to mutations in the glucokinase gene is a relatively mild form of diabetes with mild fasting hyperglycemia and IGT in the majority. It is rarely insulin requiring and rarely has vascular complications. Clinical studies indicate that the genetic or primary defect in MODY is characterized by deranged and deficient insulin secretion and not by insulin resistance and that there are quantitative and qualitative differences in insulin secretory defects which differentiate subjects with MODY due to glucokinase mutations from those with mutations in the gene on chromosome 20q. These differences correlate with the severity of diabetes between these two genetic forms of MODY.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31930/1/0000883.pd

METABOLIC EFFECTS OF SULFONYLUREAS IN NORMAL MEN and IN VARIOUS TYPES OF DIABETIC PATIENTS

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73037/1/j.1749-6632.1957.tb54592.x.pd

INTERMITTENT ALDOSTERONISM IN PERIODIC PARALYSIS : DEPENDENCE OF ATTACKS ON RETENTION OF SODIUM, AND FAILURE TO INDUCE ATTACKS BY RESTRICTION OF DIETARY SODIUM

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32503/1/0000591.pd

Neonatal diabetes mellitus with pancreatic agenesis in an infant with homozygous IPF-1 Pro63fsX60 mutation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75447/1/j.1399-5448.2009.00526.x.pd

Gastrointestinal/pancreatic hormone concentrations in the portal venous system of nine patients with organic hyperinsulinism

Percutaneous transhepatic sampling of blood in the portal venous system (TPVS) was used to; (1) localize hormone secreting tumors and help in differentiating tumors from diffuse disease (nesideoblastosis and hyperplasia with adenomata) in 9 patients with fasting hypoglycemia and hyperinsulinism, and (2) study the concentration and distribution of the immunoreactive peptides: insulin (IRI), gastrin (IG), glucagon (IRG), pancreatic polypeptide (hPP), and somatostatin (SRIF-LI), in the venous drainage of the uninvolved portion of the pancreas and GI tract. Localized elevations of IRI (64-920 [mu]U/ml) predicted tumor localization in 6 patients with single tumors that were not demonstrable angiographically. In one patient with nesideoblastosis and another with islet cell hyperplasia with adenoma, elevated IRI concentrations at multiple locations suggested a diffuse or multicentric process. Elevations of SRIF-LI in the same region as IRI elevations in one patient and of IRG in another patient suggested that these tumor produced two hormones. Some problems in the interpretation of portal venous insulin concentrations are discussed. The locations of maximum portal venous system plasma concentrations and portal-arterial gradients (mean +/- SE pg/ml) in five patients with small single insulinomas were: IG, gastrocolic trunk (126 +/- 27, 46 +/- 22); IRG, proximal splenic vein (130 +/- 30, 47 +/- 13) and gastrocolic trunk (131 +/- 23, 60 +/- 13); hPP, portal vein (164 +/- 48, 49 +/- 22); SRIF-LI, superior mesenteric vein (186 +/- 50, 57 +/- 20) and gastrocolic trunk (178 +/- 59, 55 +/- 21). It is concluded; (1) TPVS can be used successfully to localize single insulin-secreting tumors of the pancreas and to help distinguish them from diffuse disease but problems in such differentiation do occur, (2) circulating SRIF-LI and IRG are derived from both the pancreas and the gut, IG predominantly from the proximal gut and hPP from the head of the pancreas, and (3) The data provide new information for the interpretation of portal insulin concentrations in patients with organic hyperinsulinism and of hormone concentrations for localization of peptide-producing tumors of the pancreas other than insulinomas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24249/1/0000512.pd