Ketone and lactate metabolism: an exchange of conclusions.
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Acetoacetates↗
Biomedical subjects
R Nosadini
Publications and source records attributed to R Nosadini.
Role of hyperglycemia and insulin resistance in determining sodium retention in non-insulin-dependent diabetes.
Sodium retention has been advocated to give rise to hypertension in humans. Increases in blood glucose and insulin concentrations ensue in the stimulation of sodium reabsorption by the kidney. Although the combined occurrence of hyperglycemia and hyperinsulinemia, frequently secondary to insulin resistance with regard to carbohydrate metabolism, is a hallmark of non-insulin dependent diabetes (NIDDM), the role of these abnormalities in determining an impaired natriuresis in NIDDM is not yet fully understood. We studied sodium homeostasis in 14 control subjects and 59 NIDDM normotensive, normoalbuminuric patients who were divided into two groups with markedly impaired (Group 2 NIDDM: 30) and less severely impaired (Group 1 NIDDM: 29) insulin sensitivity during euglycemic-hyperinsulinemic (80 to 90 microU/ml plasma insulin) clamp. A hyperglycemic (9 mmol/liter plasma glucose)--nearly euinsulinemic (20 to 40 microU/ml plasma insulin) clamp was also performed in the same 14 controls and in two cohorts of 22 Group 2 and 17 Group 1 NIDDM patients. The two groups of patients had similar overnight fasting glucose levels (Group 1 NIDDM vs. Group 2 NIDDM: 176 +/- 13 vs. 185 +/- 15 mg/dl, mean +/- SE). Conversely, overnight fasting plasma insulin was significantly higher in Group 2 NIDDM than in Group 1 NIDDM patients (Group 1 NIDDM vs. Group 2 NIDDM: 12 +/- 3 vs. 18 +/- 3 microU/ml, P < 0.05). Both NIDDM Groups had higher plasma glucose and insulin than controls (75 +/- 4 mg/dl and 6 +/- 3 microU/ml). Blood pressure levels and albumin excretion rates were slightly but significantly higher in Group 2 NIDDM, but not in Group 1 NIDDM patients, than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The effects of different plasma insulin concentrations on lipolytic and ketogenic responses to epinephrine in normal and type 1 (insulin-dependent) diabetic humans.
This study was performed to verify: (1) the ability of different insulin concentrations to restrict the lipolytic and ketogenic responses to exogenous epinephrine administration; (2) whether the ability of insulin to suppress the lipolytic and ketogenic responses during epinephrine administration is impaired in Type 1 (insulin-dependent) diabetic patients. Each subject was infused on separate occasions with insulin at rates of 0.2, 0.4, and 0.8 mU.kg-1.min-1 while normoglycaemic. To avoid indirect adrenergic effects on endocrine pancreas secretions, the so-called "islet clamp" technique was used. Rates of appearance of palmitic acid, acetoacetate, and 3-hydroxybutyrate were simultaneously measured with an infusion of 13C-labelled homologous tracers. After a baseline observation period epinephrine was exogenously administered at a rate of 16 ng.kg-1.min-1. At low insulin levels (20 microU/ml) the lipolytic response of comparable magnitude was detected in normal and Type 1 diabetic patients. However, the ketogenic response was significantly higher in Type 1 diabetic patients. During epinephrine administration, similar plasma glucose increments were observed in the two groups (from 4.74 +/- 0.53 to 7.16 +/- 0.77 mmol/l (p less than 0.05) in Type 1 diabetic patients and from 4.94 +/- 0.20 to 7.11 +/- 0.38 mmol/l (p less than 0.05) in normal subjects, respectively). At intermediate insulin levels (35 microU/ml) no significant differences were found between Type 1 diabetic patients and normal subjects, whereas plasma glucose levels rose from 4.98 +/- 0.30 to 6.27 +/- 0.66 mmol/l (p less than 0.05) in Type 1 diabetic patients, and from 5.05 +/- 0.13 to 6.61 +/- 0.22 mmol/l (p less than 0.05) in normal subjects. At high insulin levels (70 microU/ml) the lipolytic response was detectable only in Type 1 diabetic patients; the ketogenic response was reduced in both groups. During the third clamp, a significant rise in plasma glucose concentration during epinephrine infusion was observed in both groups. In conclusion this study shows that at low insulin levels Type 1 diabetic patients show an increased ketogenic response to epinephrine, despite their normal nonesterified fatty acid response. Instead, high insulin levels are able to restrict the ketogenic response to epinephrine in both normal and Type 1 diabetic subjects, although there is a still detectable lipolytic response in the latter. In the presence of plasma free insulin levels that completely restrict the ketogenic response in the same group, there is still a distinct glycaemic response. Plasma insulin levels in Type 1 diabetic patients are a major determinant of the metabolic response to epinephrine.
Acetoacetates↗
Relationships among natriuresis, atrial natriuretic peptide and insulin in insulin-dependent diabetes.
Insulin-dependent diabetic patients have a large exchangeable body sodium pool, secondary to sodium retention. The pathogenesis of impaired natriuresis in insulin dependent diabetes remains to be elucidated. The present study examines the role of hyperinsulinemia, impaired atrial natriuretic release, and resistance to atrial natriuretic peptide action in determining sodium retention in normotensive and hypertensive insulin-dependent diabetic patients. Eight insulin-dependent diabetic patients had significantly higher daily sodium excretion rate (147 +/- 16 mmol/day; mean +/- SE) during conventional insulin treatment (daily plasma glucose: 11.6 +/- 1.2 mmol/liter; daily plasma insulin: 27 +/- 3 microU/ml) than during intensified insulin treatment (daily sodium excretion rate: 91 +/- 12, P less than 0.01; daily plasma glucose: 6.8 +/- 0.7, P less than 0.01; daily plasma insulin: 44 +/- 4, P less than 0.01). Daily sodium excretion rate was also significantly lower (107 +/- 13, P less than 0.01) in the same diabetic patients during intensified insulin treatment along with hyperglycemic clamp (daily plasma glucose: 12.8 +/- 0.3, NS; plasma insulin 48 +/- 4, P less than 0.01). Seven control subjects had lower extracellular liquid volume than eight insulin-dependent diabetic patients (11.0 +/- 0.8 l/1.73 m2 vs. 14.8 +/- 0.9, P less than 0.05) and also had baseline plasma atrial natriuretic peptide concentrations (18 +/- 5 pg/ml vs. 37 +/- 4, P less than 0.05). Atrial natriuretic peptide response to saline challenge was blunted in insulin-dependent diabetic patients when saline was administered on the basis of body surface area (90 mmol/1.73 m2.90 min) but not when administered on the basis of extracellular liquid volume (ECV) (8.2 mmol/liter ECV.90 min).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Clustering of risk factors in hypertensive insulin-dependent diabetics with high sodium-lithium countertransport.
Diabetic nephropathy is more common in patients with a positive family history of hypertension and with elevated red blood cell sodium-lithium countertransport, a marker of risk for essential hypertension. To evaluate whether there is a relationship between this cation transport system and indicators of risk of renal and cardiovascular complications in diabetic patients before the development of clinical proteinuria, we studied 31 type 1 (insulin-dependent) diabetic patients with arterial hypertension, without clinical proteinuria and 12 normotensive normoalbuminuric diabetic patients. Sodium-lithium countertransport activity was significantly higher in hypertensive patients (0.43 +/- 0.03 mmol/l RBC x hr) than in normotensive patients (0.23 +/- 0.03; P less than 0.001). To better explore the nature of the association between this transport system and arterial hypertension, hypertensive patients were divided in two groups, with high (greater than 0.41 mmol/l RBC x hr) or normal (less than 0.41) sodium-lithium countertransport activity. The two groups of hypertensive diabetics were similar in age, sex, body mass index and blood pressure levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Antiporters↗
Forearm ketone body metabolism in normal and in insulin-dependent diabetic patients.
In insulin deficiency, there is excessive arterial delivery of free fatty acid (FFA) to muscles where they are converted to acetoacetyl-CoA and acetyl-CoA. These intermediates may be metabolized further to acetoacetate and beta-hydroxybutyrate, which can be released into the venous circulation. When ketone body (KB) tracers are infused in vivo, they are diluted across muscle tissue. This dilution may be due to 1) KB newly formed within muscle (ketogenesis); 2) exchange of tracer between labeled and unlabeled acetyl-CoA and acetoacetyl-CoA, intermediates common to the metabolism of both FFA and KB (pseudoketogenesis). Thus this study assessed whether such label exchange could be detected across the human forearm and whether an increased delivery of FFA in insulin-sufficient controls provoked dilution of labeled KB tracer comparable to that observed in insulin-deficient diabetics. Five normal and five insulin-dependent diabetic (IDDM) subjects were infused with labeled [3,4-13C2]-acetoacetate. [13C]KB enrichments were lower in forearm vein than in the artery, and dilution of labeled KB was always higher than that which could be explained by arterial-venous differences of unlabeled KB. When arterial FFA concentrations in normals were raised (Intralipid+heparin) to values comparable to those of the diabetics, no additional increase in forearm arteriovenous dilution of labeled KB was observed. Neither in the basal state nor under conditions of increased plasma FFA were we able to detect venous appearance of KB labeled in the first and in the second carbon atoms, a necessary consequence of pseudoketogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Close relationship between microalbuminuria and insulin resistance in essential hypertension and non-insulin dependent diabetes mellitus.
The aim of this study was to investigate the relationships among insulin resistance and albumin excretion rate in 25 nondiabetic patients with essential hypertension and in 28 patients with non-insulin dependent diabetes mellitus (NIDDM). Two groups of healthy subjects matched for age, sex, and weight served as controls. Patients with essential hypertension were divided into two subgroups: without (H1) and with (H2) microalbuminuria. Diabetic patients were divided into four subgroups: those with normoalbuminuria without (NIDDM1) and with (NIDDM2) hypertension and those with microalbuminuria without (NIDDM3) and with (NIDDM4) hypertension. Whole-body glucose utilization during euglycemic hyperinsulinemic clamp (40 mU/m2/min insulin infusion) was calculated by tracer dilution techniques (6,6 2H2 glucose tracer continuous infusion) and was significantly lower in hypertensives with microalbuminuria than in those without (H2 versus H1 versus controls: 3.41 +/- 0.51 versus 6.52 +/- 0.62 versus 7.03 +/- 0.48 mg/kg/min; mean +/- SE). Whole-body glucose utilization in NIDDM patients--NIDDM4 versus NIDDM3 versus NIDDM2 versus NIDDM1 versus controls--was: 1.86 +/- 0.31 versus 2.21 +/- 0.39 versus 2.01 +/- 0.40 versus 5.98 +/- 0.77 versus 5.52 +/- 0.92 mg/kg/min (mean +/- SE). Whereas the first three subgroups did not differ among themselves, they had significantly lower glucose utilization than did the normotensive NIDDM1 patients without microalbuminuria and nondiabetic controls (P < 0.01). Hypertensives with microalbuminuria had higher Vmax of sodium-lithium countertransport (Na/Li CTT) in red blood cells than did both hypertensives without microalbuminuria and controls. It was also observed that NIDDM patients with microalbuminuria had higher Vmax of Na/Li CTT than did NIDDM patients without microalbuminuria and controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Albuminuria↗
Ketone body metabolism in NIDDM. Effect of sulfonylurea treatment.
We assessed the metabolism of the two KBs, AcAc and 3-BOH; the relationships between ketogenesis and FFA inflow rate; and the effect of chronic sulfonylurea treatment in mild NIDDM patients (plasma glucose less than 10 mM). We studied 10 nonobese NIDDM patients in a crossover, randomized, double-blind, placebo-controlled fashion. Each patient was studied 4 times: after a run-in period with placebo, after 3 mo of placebo treatment, after 3 mo of glibenclamide treatments, respectively, and after 3 mo of sulfonylurea treatment during an acute exogenous Intralipid infusion. Ten normal, nondiabetic subjects served as the control group. Glibenclamide treatment decreased plasma FFAs. When these substrates were exogenously increased, plasma FFAs were comparable with placebo and baseline concentrations. In NIDDM patients, baseline and placebo blood total KB concentration was significantly higher than in control subjects (216 +/- 22 and 244 +/- 25, respectively vs. 127 +/- 18 microM; P less than 0.01). Glibenclamide treatment significantly decreased total KBs to 177 +/- 19 microM (P less than 0.05). When FFAs were exogenously increased, total KBs were similar to the placebo and baseline period. In the baseline study, the AcAc/3-BOH ratio was 0.72 +/- 0.06 in control subjects, whereas in NIDDM patients, the ratio was 1.61 +/- 0.13 at baseline (P less than 0.001 vs. control subjects), 1.66 +/- 0.15 during placebo, 1.57 +/- 0.09 during glibenclamide (NS vs. baseline), and 1.51 +/- 0.23 during glibenclamide plus placebo FFAs. Both the AcAc interconversion rate to 3-BOH and the 3-BOH interconversion rate to AcAc were significantly lower in NIDDM patients than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Renal hemodynamics and albumin excretion rate in patients with diabetes secondary to acquired pancreatic disease.
OBJECTIVE--To assess kidney function and AER in patients with PD. RESEARCH DESIGN AND METHODS--Thirty-three patients with PD (age 52 +/- 7 yr, duration of disease 11 +/- 6 yr, BMI 24 +/- 3 kg/m2) and 33 patients with IDDM were matched for sex, BMI, and duration of disease. GFR and RPF were determined by single injection of [51Cr]EDTA and [125I]hippurate. AER was measured by radioimmunoassay in a single timed overnight urine collection. RESULTS--GFR and RPF were, respectively, 113 +/- 35 and 441 +/- 145 ml.min-1.73 m2 in patients with PD and 123 +/- 30 and 549 +/- 94 (P < 0.001) in IDDM. FF was significantly higher in patients with PD (0.26 +/- 0.05 vs. 0.22 +/- 0.03; P < 0.001). Prevalence of hyperfiltration (GFR > 135 ml.min-1.1.73 m2) was similar in both groups (30% in patients with PD vs. 28% in those with IDDM). Geometric mean of urinary AER was 10.4 micrograms/min (range 1-186) in patients with PD and 11.2 (1-198) in IDDM patients. Some 30.3% of patients with PD and 18% of those with IDDM were microalbuminuric (AER > 20 micrograms/min). By multiple regression analysis, AER was significantly related to systolic (P < 0.04) and diastolic blood pressure (P < 0.01) and to BMI (P < 0.03) in patients with PD. Retinopathy was more frequent in microalbuminuric patients with PD than in those without elevated AER. CONCLUSIONS--We suggest that early renal abnormalities occur similarly in patients with PD and IDDM.
Adult↗
Prevalence of hypertension in type 1 (insulin-dependent) diabetes mellitus.
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Adult↗
Diabetes mellitus and hypertension: a physiologic basis for a rational therapeutic approach.
The basic mechanisms that initiate and sustain hypertension in the diabetic population are poorly understood. Obesity, insulin, genetic factors, and abnormalities in calcium homeostasis may contribute, and could be related to an elevated Na+/H+ antiport activity. In the first study described in this investigation, hypertensive subjects with insulin-dependent diabetes mellitus (IDDM) who had an elevated Na+/Li+ countertransport activity were found to have a lower whole body glucose utilization, a lower insulin-stimulated forearm carbohydrate oxidation, larger ultrasound kidney volume, and increased left ventricular mass index when compared with hypertensive IDDM subjects with a normal Na+/Li+ countertransport activity or normotensive IDDM subjects. Thus an elevated Na+/Li+ countertransport activity appears to identify a subset of IDDM patients who are more susceptible to the development of the renal and cardiac complications associated with hypertension. This underlines the importance of choosing an appropriate antihypertensive therapy that will not produce a deterioration in glucose and lipid metabolism. In the second part of the report, results are presented for the treatment of hypertensive patients with non-insulin-dependent diabetes mellitus with doxazosin. The selective alpha 1-inhibitor produced a significant reduction in blood pressure, together with favorable changes in the serum lipid profile. As a result, the calculated risk of developing coronary heart disease was significantly reduced. Throughout the study no patients required a dose reduction or discontinuation of doxazosin because of side effects, and no clinically significant changes in laboratory tests were apparent. Thus doxazosin could be considered a useful antihypertensive agent in hypertensive patients with IDDM who are insulin-resistant and who have renal and cardiac abnormalities.
Antihypertensive Agents↗
Myocardial metabolism in type 1 diabetic patients without coronary artery disease.
Myocardial exchange of metabolic substrates was investigated in eight Type 1 diabetic patients with angiographically normal coronary arteries and seven normal control subjects, after an overnight fast. Simultaneous samples of arterial and coronary sinus blood were collected for analysis of the major metabolic substrates. Myocardial blood flow was measured by the thermodilution technique. Although the Type 1 patients were hyperglycaemic (10.0 +/- 2.0 (+/- SE) mmol I-1) myocardial glucose uptake was lower than in control subjects (27 +/- 6 vs 42 +/- 5 mumol min-1 1.73 m-2, p less than 0.05). The net balance of lactate and pyruvate across the myocardium showed a net release in Type 1 patients (13.4 +/- 2.7 mumol min-1 1.73 m-2 and 1.3 +/- 0.2 mumol min-1 1.73 m-2, respectively) and a net uptake in control subjects (2.2 +/- 0.7 mumol min-1 1.73 m-2 and 3.5 +/- 0.3 mumol min-1 1.73 m-2, both p less than 0.01). Myocardial uptake of ketone bodies was significantly higher in diabetic patients (37.0 +/- 6.3) mumol min-1 1.73 m-2) than in control subjects (10.1 +/- 3.4 mumol min-1 1.73 m-2, p less than 0.01). Non-esterified fatty acid (NEFA) uptake was significantly greater in the diabetic patients than in control subjects (44.1 +/- 7.0) vs 24.1 +/- 5.1 mumol min-1 1.73 m-2, p less than 0.01). Net balance of glucose, lactate, and pyruvate across the myocardium was inversely and significantly related to that of NEFAs and ketone bodies (p less than 0.01). Myocardial carbohydrate uptake is markedly impaired in Type 1 diabetic patients with angiographically intact coronary vessels. Ketones and NEFA represent the major fuel for the diabetic myocardium. Thus, in diabetes, myocardial lactate metabolism may be profoundly altered independently of coronary artery disease.
Blood Glucose↗
Insulin resistance is associated with high sodium-lithium countertransport in essential hypertension.
The nature of the association between essential hypertension and insulin resistance remains unknown. We measured plasma glucose and insulin levels after an oral glucose tolerance test (OGTT), as well as insulin sensitivity (using a euglycemic hyperinsulinemic clamp), glucose turnover (Rd; using [6,6-2H2]- and [3-3H]glucose isotopic dilution), and forearm net balance of glucose (using arterial-venous difference) in 22 hypertensive patients with high (H2) red blood cell (RBC) sodium-lithium countertransport (Na(+)-Li+ CT; greater than 0.41 mmol.l RBC-1.h-1), 21 hypertensive patients with normal (H1) Na(+)-Li+ CT, and 22 normotensive controls (C). After OGTT, H2 patients had higher plasma glucose and insulin levels than H1 and C. During euglycemic hyperinsulinemia (approximately 100 microU/ml) Rd was lower in H2 [21.7 +/- 1.4 (SE) mumol.kg-1.min-1] than in H1 (44.3 +/- 2.9; P less than 0.01) and C (48.1 +/- 3.0; P less than 0.01), and an inverse correlation was found between rates of Na(+)-Li+ CT and Rd in H1 and H2 (rs = -0.76; P less than 0.01). Forearm glucose uptake was 40-50% lower in H2 compared with H1 and C (P less than 0.01). Lactate concentration increased more in C (from 511 +/- 24 to 1,207 +/- 69 microM) and in H1 (from 564 +/- 40 to 1,122 +/- 99) than in H2 (from 581 +/- 42 to 950 +/- 102, P less than 0.05 vs. both). Forearm blood flow increased more in C (31%, P less than 0.05) and H1 (22%, P less than 0.05) than in H2 (12%).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Sodium-lithium countertransport and cardiorenal abnormalities in essential hypertension.
The rate of red blood cell sodium-lithium countertransport is elevated only in a subgroup of patients with essential hypertension. We have therefore compared renal and cardiac function and morphology in two groups of hypertensive patients with high (n = 23) or normal (n = 22) sodium-lithium countertransport (mean +/- SEM: 0.61 +/- 0.10 versus 0.29 +/- 0.07 mmol/l red blood cells.hr). The two groups were similar in age, sex distribution, body mass index, smoking habit, duration of hypertension, and actual levels of untreated blood pressure. Hypertensive patients with elevated sodium-lithium countertransport activity showed elevated glomerular filtration rate (118 +/- 2 versus 109 +/- 2 ml/min.1.73 m2; p less than 0.001), albumin excretion rate (23 +/- 3 versus 14 +/- 2 micrograms/min; p less than 0.001), larger kidney volume (250 +/- 15 versus 203 +/- 13 ml.1.73 m2; p less than 0.01), lower lithium clearance rate (26.7 +/- 0.3 versus 28.9 +/- 0.3 ml/min.1.73 m2; p less than 0.01), and higher total body exchangeable sodium (2,716 +/- 33 versus 2,485 +/- 41 mmol.1.73 m2; p less than 0.01). Left ventricular mass index (139 +/- 6 versus 119 +/- 6 g/m2; p less than 0.05), relative wall thickness (0.39 +/- 0.05 versus 0.29 +/- 0.04 cm; p less than 0.001), and left posterior wall plus intraventricular septum thickness (2.02 +/- 0.04 versus 1.76 +/- 0.03 cm; p less than 0.05) were also higher in patients with high sodium-lithium countertransport. Hypertensive patients with normal sodium-lithium countertransport had renal and cardiac parameters similar to those of a normotensive control group (n = 21) except for a higher glomerular filtration rate and left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Insulin-dependent diabetes mellitus and hypertension.
Contrasting results have been reported regarding the prevalence of hypertension in insulin-dependent diabetes mellitus (IDDM), showing a slightly higher or normal percentage of IDDM patients with elevated blood pressure levels than in the general population. Most of the cross-sectional and prospective studies on the prevalence of hypertension in IDDM show an association between microalbuminuria and elevated blood pressure levels. However, it is not clear whether hypertension is simply secondary to kidney damage or whether hypertension occurs with or even before the development of impaired kidney function. Patients with IDDM have a higher exchangeable body Na+ pool. Na+ retention in IDDM is accounted for by several metabolic and hormonal abnormalities such as hyperglycemia, hyperketonemia, hyperinsulinemia, altered secretion, and resistance to atrial natriuretic peptide. High blood pressure appears to be dependent, at least at some phase, on expansion of extracellular fluid volume as a consequence of defects in the renal secretion of Na+ and water. On the other hand, a tendency toward Na+ retention characterizes all patients with IDDM, whereas hypertension develops only in a subgroup of diabetic patients. One possible explanation for these findings is that a genetic predisposition plays a role in creating susceptibility to hypertension and perhaps to diabetic nephropathy independent of diabetes, even if Na+ retention can further deteriorate this susceptibility to hypertension. With regard to this issue, it has recently been suggested that the risk of kidney disease in patients with IDDM is associated with a genetic predisposition to hypertension. Furthermore, diabetic nephropathy occurs in familial clusters, because diabetic siblings of nephropathic diabetic patients show a higher frequency of diabetic nephropathy than the diabetic siblings of nonnephropathic diabetic patients. One of the possible genetic markers that could be useful to identify the diabetic patients with susceptibility to hypertension and diabetic nephropathy is the Na+(-)Li+ countertransport activity in erythrocytes.
Biological Transport↗
Resistance to the actions of atrial natriuretic factor in insulin-dependent diabetic hypertensives and improvement with angiotensin converting enzyme inhibitor treatment.
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Adolescent↗
Effects of atrial natriuretic peptide infusion on kidney function in normotensive type 1 (insulin-dependent) diabetic patients before and after enalapril treatment.
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Adult↗
[Cardiac metabolism in patients with insulin-dependent diabetes without coronary atherosclerosis].
UNLABELLED: Eleven insulin-dependent diabetic patients (IDDM) with angiographically normal coronary arteries and normal echocardiographic dipyridamole test, and 12 normal controls were studied at rest and after atrial pacing. Simultaneous sampling from arterial and coronary sinus blood was performed. In IDDM patients, despite hyperglycemia, myocardial glucose uptake was slightly lower than in controls. This process was significantly activated in both groups by atrial pacing. The isotopically calculated net flux of lactate across myocardium, in agreement with the net balance value based on unlabeled lactate-pyruvate arterio-venous differences, showed a net uptake in controls (3.5 +/- 0.6 mumol/min/1.73 m2) and a net release in IDDM (12.4 +/- 2.6; p less than 0.01). Atrial pacing stimulated lactate uptake in both groups. Myocardial uptake of ketone bodies was significantly higher in IDDM than in controls (37.0 +/- 6.3 mumols/min/1.73 m2 vs 10.1 +/- 3.4; p less than 0.01). Free fatty acid uptake was also significantly greater in IDDM than in controls (44.1 +/- 7.0 mumols/min/1.73 m2 vs 24.1 +/- 5.1; p less than 0.01). Alanine and branched chain amino-acids were released by diabetics but not by control hearts at rest. The normalization of blood glucose concentrations restored normal patterns of lactate and ketone body kinetics across diabetic myocardium. IN CONCLUSION: at rest, myocardial lactate and aminoacids uptake is markedly impaired in IDDM without coronary artery disease; the metabolic abnormalities of the diabetic myocardium is not a primary phenomenon but rather a consequence of hypoinsulinemia and hyperglycemia because insulin administration, resulting in normoglycemia, restored normal patterns of cardiac metabolism.
Adult↗