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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was undertaken to determine whether alterations in ketone body utilization and hepatic production, independent of the FFA load, were also involved in the development of fasting ketosis. Plasma Beta-OH butyric acid (Beta-OHB) increased to 2.5-4.5 mM and plasma FFA to 1,000-1,400 muEq/L. in normal weight individuals after five to seven days' starvation and in obese subjects after ten to fourteen days' fasting. Acute elevations fo the plasma FFA greater than 1,500 muEq/L. for sixty minutes in fed normal weight and obese subjects with a fat meal-heparin regimen resulted in peak elevations of plasma Beta-OHB (0.25-0.45mM), only 10 percent of that seen during fasting. When plasma FFA were lowered acutely during fasting with the antilipolytic agent Pyrazole to control levels (400-600 muEq/L.), plasma Beta-OHB decreased 35 plus or minus 5 per cent. Comparable lowering of plasma FFA in normal weight or obese starved subjects given dexamethasone to maintain elevated fasting plasma insulin levels resulted in an 87 plus or minus 3 per cent decrease in plasma Beta-OHB. Similar studies in obese fasted subjects pretreated with an intravenous infusion of insulin (1.0 U/hr. for eight hours) before receiving Pyrazole resulted in a 65 plus or minus 5 per cent decrease in plasma Beta-OHB. Plasma Beta-OHB half-life, determined after injections of 12 gm. Beta-OHB, increased significantly during fasting (110 plus or minus 15 minutes) and was decreased when the fasting subjects were maintained on dexamethasone (65 plus or minus 7 minutes). These studies indicate that accelerated hepatic ketogenesis during starvation is a result of both enhanced activity of the enzymatic system(s) involved in ketone body production as well as an increased FFA load. The increase in plasma Beta-OHB during fasting reflects not only an accelerated rate of hepatic ketogenesis but also an impairment of peripheral utilization, both processes apparently being sensitive to insulin. Diabetes 24:10-16, January, 1975.
Diabetes 1975 Jan
PMID:Physiologic mechanisms in the development of starvation ketosis in man. 112 May 41

To evaluate the relationship of blood ketone bodies with diabetic control and endogenous insulin secretion, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), fasting serum C-peptide (CPR), blood total ketone-bodies (TKB), blood acetoacetate (AcAc) and blood 3-hydroxybutyrate (3-OHB) were compared in 78 outpatients with non-insulin-dependent diabetes mellitus (NIDDM) treated with diet (n = 13), sulfonylurea (n = 52) and insulin (n = 13). TKB, AcAc and 3-OHB in patients treated with insulin were significantly higher than in patients treated with diet or sulfonylurea. In patients given diet therapy, log 3-OHB showed significant negative correlations with FPG, HbA1c and CPR. In patients treated with sulfonylurea, log 3-OHB showed significant positive correlations with FPG and HbA1c, but not with CPR. In patients treated with insulin, there were no correlations of log 3-OHB with FPG, HbA1c and CPR. For evaluation of the metabolic state in diabetes mellitus, measurement of blood ketone bodies is useful, and moreover necessary, in addition to diabetic control or determination of the endogenous insulin level.
Diabetes Res 1991 Sep
PMID:Blood ketone bodies in NIDDM: relationship with diabetic control and endogenous insulin secretion. 182 41

The aim of this study was to investigate the pathogenesis of hypoaldosteronism in diabetes. Endogenous elevation of plasma renin activity and exogenous corticotropin were used to study steroidogenesis. Observations were made over 12 yr on the evolution and treatment of hyperkalemia in a diabetic subject. In 1977, potassium, baseline cortisol, aldosterone, and renin activity were normal; renin activity increased normally with posture; and cortisol responded normally to ACTH infusion. Nine yr later, persistent hyperkalemia was documented. Upright renin activity was elevated to 5.26 ng.L-1.s-1, with concomitant elevation of 18-hydroxycorticosterone (18-OHB) and a low-normal aldosterone level. One hour after administration of 0.25 mg i.m. cosyntropin, cortisol increased normally, aldosterone increased from 220 to 360 pM, and 18-OHB increased from 3700 to 4800 pM. During treatment with fludrocortisone, fludrocortisone with furosemide, and furosemide alone, improvement of hyperkalemia was noted. Endogenous hyperreninemia and basal elevations of 18-OHB, accompanied by limited aldosterone responsiveness to renin and ACTH, suggest the presence of a partial corticosterone methyl oxidase type II defect. Evolution of hyperkalemia between 1977 and 1986 suggests this defect was acquired.
Diabetes Care 1990 Jul
PMID:Acquired partial corticosterone methyl oxidase type II defect in diabetes mellitus. Case of hyperreninemic hypoaldosteronism. 216 93

Previous studies have suggested that skeletal muscle may be responsible for as much as 25% of ketone body (KB) production in poorly controlled diabetes. In the present studies, acetoacetate (AcAc) and beta-hydroxybutyrate production was quantitated in the canine hindlimb from surgically placed arterial and venous catheters in conscious insulin-withdrawn diabetic (n = 5) and 4-day fasted (n = 7) dogs. A two-pool modeling technique, using simultaneous infusions of 13C acetoacetate and 14C beta-hydroxybutyrate (beta OHB) was employed to quantitate total body and hindlimb KB kinetics. Total KB production was 9.4 and 39.3 mumol.kg-1.min-1 in the fasted and diabetic animals, respectively. Hindlimb KB production was negligible in both groups. The two-pool model estimates of hindlimb KB utilization were similar to the values obtained by an arterial-venous difference calculation. In conclusion, the hindlimb does not contribute to de novo synthesis of KBs in either fasted or diabetic dogs. Since species differences in KB metabolism occur, it is possible that muscle may be a site for KB production in humans.
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PMID:Metabolism of ketone bodies by skeletal muscle in starvation and uncontrolled diabetes. 221 51

A film test for the rapid detection of plasma/serum 3-hydroxybutyrate (3-OHB) has been developed. The film contains NAD, nitro blue tetrazolium, 3-OHB dehydrogenase, and diaphorase, and the surface is coated with modified biomembrane and can detect 50-1500 microM 3-OHB within 2-3 min. One drop or 50 microliters of plasma/serum or blood is applied to the film, and the violet color is read via reflectance meter after 2 min. Plasma/serum samples greater than 1500 microM 3-OHB can be measured by dilution with saline. In blood with 40% hematocrit, the color developed is 50% less than with plasma/serum, and this was adjusted in the reflectance meter. A good correlation (r = 0.99) was observed between results with automated and film methods and between visual methods and reflectance meter. In insulin-dependent diabetes mellitus, all 3 subjects with positive ketonuria (+ +), 8 of 12 subjects with mild ketonuria (+), and 7 of 25 subjects without ketonuria exhibited elevation of 3-OHB in blood greater than 200 microM. The results indicate that 3-OHB film is valuable not only in the emergency room for the differential diagnosis between ketoacidotic and nonketotic hypersomolar coma but also as a marker for insulin dependency, energy dependency on fatty acid compared with glucose, and metabolic control of diabetes.
Diabetes Care 1990 May
PMID:Development of stable film test for rapid estimation of blood or plasma 3-hydroxybutyrate. 235 Oct 30

offlated hypoaldosteronism with or without hyperkalemia in patients with diabetes mellitus has been shown to exist occasionally without hyporeninemia. To assess in detail the adrenal function in this disorder, the responses of plasma aldosterone (PA) and its precursor steroids to angiotensin II (AII) infusion and adrenocorticotropic hormone (ACTH) injection were studied in seven patients with asymptomatic normoreninemic hypoaldosteronism (ANH) and 11 age-matched normal subjects. The ANH diabetic patients had, by definition, a low PA level after furosemide (80 mg orally) plus upright posture (4 hours) stimulation, low PA and high plasma renin activity (PRA) increases after the stimulation (a low delta PA/delta PRA ratio), and normokalemia. Plasma inactive renin and the inactive renin/total renin ration were similar in the ANH diabetic patients and in the normal subjects. Under the pre-AII condition, plasma DOC and corticosterone levels tended to be low, and the plasma 18-OHB and PA levels were low in the ANH diabetic patients compared with the normal subjects. The ratio of plasma 18-OHB to PA was similar in the two groups. All infusion produced no increases in plasma 18-OHB and PA in the ANH diabetic patients, whereas the infusion caused dose-dependent increases in these steroids in the normal subjects. Plasma DOC and corticosterone levels remained unchanged during AII infusion in the two groups. ACTH injection produced appropriate PA increases relative to the basal PA in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Unresponsiveness of plasma mineralocorticoids to angiotensin II in diabetic patients with asymptomatic normoreninemic hypoaldosteronism. 298 80

We have examined changes in plasma ketone bodies and their related metabolites after the ingestion of a mixed meal in normal and NIDDM (non-insulin-dependent diabetes mellitus) using a highly sensitive colorimetric method. In normal subjects, fasting plasma acetoacetic acid (AcAc) and 3-beta-hydroxybutyric acid (3-OHB) concentrations were 40.2 +/- 2.9 and 21.3 +/- 4.0 microM, respectively. The total carnitine level in fasting plasma was 48.2 +/- 3.2 microM and acyl/free was 0.34 +/- 0.12. These values did not change significantly after the meal. In diabetic subjects, fasting AcAc and 3-OHB levels were 57.9 +/- 3.5 and 97.9 +/- 14.7 microM, respectively and these values especially 3-OHB, decreased almost to the normal level by 4 h after the meal. The total carnitine level in the fasting plasma of diabetics was 48.7 +/- 2.8 microM and acyl/free was 0.58 +/- 0.09. Such characteristics were observed when their plasma glucose had been completely normal for more than 10 days. In patients treated with sulfonylurea, the fasting ketone body level, especially 3-OHB, was significantly lower than that of diabetics treated with insulin or diet alone, whereas the fasting plasma glucose level and its postprandial increase were higher than those of the others. These results demonstrate that measurement of the plasma ketone body (especially 3-OHB) level is a sensitive tool for monitoring the metabolic status of NIDDM.
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PMID:Postprandial changes in plasma ketone body and carnitine levels in normal and non-insulin-dependent diabetic subjects. 330 42

Hyperinsulinism frequently accompanies glucose normalization in type I diabetes but the long-term consequences of this exaggerated hormonal state are not known. To study this condition, normal dogs received constant exogenous sulfated insulin infusions for prolonged periods up to 43 weeks. During the interval and inspite of prevailing postabsorptive and fasting hypoglycemia, overt resistance to the infused insulin or loss of sensitivity did not occur. In counterring the imposed fasting hyperinsulinemia and the resulting hypoglycemia, fasting pancreatic glucagon levels rose while the fasting levels of several glucogenic precursors (lactate, pyruvate, and alanine) decreased. Fasting free fatty acid (FFA) levels were suppressed, but beta-hydroxybutyrate (beta-OHB) levels were unchanged. Body weight did not change. Most remarkably, all changes measured in the fasting levels of the hormones and metabolites reverted to normal following the cessation of exogenous sulfated insulin infusion. In addition to the hormonal and metabolite adaptations invoked by chronic exogenous hyperinsulinism in the fasting state of these normal dogs, there were interesting responses to their usual mixed meals. Of particular interest in this regard were the plasma glucose, insulin, and FFA diurnal profiles. First of all, a definite and unusual postprandial glycemic excursion occurred. Second, insulin levels were elevated some sixfold, and rather unresponsive to the meal in general. Inspite of the depressed fasting FFA levels and the absence of a postprandial rise in insulinemia, FFA showed a distinct fall after the meal. Whether the sulfated insulins infused were of the bovine or porcine species of origin made no discernible difference.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The metabolic and hormonal adaptations of normal dogs to long-term exogenous sulfated insulin infusions. 353 58

Gestational diabetes mellitus (GDM) is a nonhomogeneous entity known to affect fetal development in different ways in both rats and human beings. The degree of severity of diabetes could affect the maternal-fetal transfer of metabolic fuels and consequently influence fetal development. To study this hypothesis, pregnant rats were made diabetic by streptozocin (STZ) treatment (45 mg/kg) at day 7 of gestation and were treated with different daily doses of insulin until the 20th day of gestation, when they were killed and examined. Differences in plasma glucose levels in the groups studied were not accompanied by differences in plasma glycerol, beta-hydroxybutyrate (beta-OHB), or total amino acid levels in mothers or their fetuses. Fetal/maternal ratios of these circulating fuels were not modified by maternal diabetes, whereas the glucose level was enhanced in diabetic rats not treated with insulin. Placental glucose transfer was studied directly with a recently reported in situ experimental design and was found to increase linearly with maternal glycemia, independently of whether this was modified by insulin treatment or by acute intravenous (i.v.) infusion of glucose in normal animals. Lactate production by the fetal/placental unit decreased in proportion to the glucose level in the maternal circulation. The present data indicate that the diabetic condition of the mother rat does not modify the mechanisms of placental transfer of metabolic fuels to the fetus, and that the actual transfer is mainly dependent on the concentrations of these fuels in the maternal circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Jun
PMID:Relationship between maternal and fetal fuels and placental glucose transfer in rats with maternal diabetes of varying severity. 388 41

[3-14C]acetoacetate (AcAc) and beta-[3-14C]hydroxybutyrate (beta-OHB) administration, measurements of labeled AcAc and beta-OHB in blood, and kinetic modeling have been used to investigate ketone body (KB) metabolism in five normal, five obese, and eight insulin-withdrawn diabetic subjects. Diabetic subjects were divided in mildly ketotic (MKD) and highly ketotic (HKD) patients according to beta-OHB blood level. A four-compartmental model successfully described the tracer kinetic data in obese and normal subjects, whereas in diabetic patients a five-compartmental model was necessary. Obese subjects showed a significantly lower (P less than 0.05) KB de novo synthesis (R30 = 159 +/- 54 (SD) mumol X min-1 X m-2) in comparison with normal subjects (282 +/- 93), but the clearance rates of AcAc (PCR1) and beta-OHB (PCR2) were similar in the two groups. R30 was 596 +/- 534 in MKD and 1,278 +/- 445 (P less than 0.01) in HKD. PCR1 was not significantly different both in MKD and HKD in comparison with normal subjects. In contrast PCR2 was markedly reduced in HKD (0 +/- 0 ml X min-1 X m-2) in comparison with MKD (1,031 +/- 615) and normal subjects (782 +/- 278). The percentage distribution of KB among various tissues inside the organism of diabetic subjects is abnormal. Both AcAc and beta-OHB recycling and mean residence time are not normal in HKD. A significant correlation was found between C-peptide and KB production in diabetes. These results suggest that a selective defect of beta-OHB peripheral utilization is important in determining and maintaining severe diabetic ketoacidosis.
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PMID:Acetoacetate and 3-hydroxybutyrate kinetics in obese and insulin-dependent diabetic humans. 392 34


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