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Biomedical subjects

R R Henry

Publications and source records attributed to R R Henry.

At least 73 records · Page 4Linked to original sources
PubMed1994

Delayed onset of insulin activation of the insulin receptor kinase in vivo in human skeletal muscle.

During the infusion of insulin in vivo, the rate of activation of glucose disposal lags significantly behind the rate of increase in serum insulin levels. To determine whether this delay was related to transcapillary transport of insulin, we determined increments in serum insulin levels, glucose disposal rates (GDR), and insulin receptor (IR) kinase activity measured during continuous infusions of insulin (40 and 120 mU.m-2.min-1) administered to 8 nondiabetic males; similar studies were done at 1,200.m-2.min-1 in 2 of the subjects. Half-maximal insulin levels were achieved at a mean of 4.9 and 7.2 min during the 40 and 120 mU.m-2.min-1 clamps, respectively, with corresponding half-maximal GDR stimulation at a mean of 59 and 47 min. Unlike the rise in insulin levels, IR kinase activation was much slower with half-maximal activity occurring at approximately 40-60 min in the 2 clamps. Thus, the rise in serum insulin levels in each clamp was much faster than the increment in either kinase activity or glucose disposal. Insulin infusion increased both IR kinase and GDR maximally approximately 10-fold, with half-maximal stimulation at approximately 3,600 and approximately 700 pM, indicating spare kinase for glucose disposal. These results demonstrate that the delay in stimulation of glucose disposal by insulin is related to a rate-limiting step between the intravascular space and the cell-surface of skeletal muscle. This may involve delayed transendothelial transport of insulin.

Adult↗
PubMed1994

Alterations in immunoreactive proinsulin and insulin clearance induced by weight loss in NIDDM.

Subjects with overt non-insulin-dependent diabetes mellitus (NIDDM) were studied in comparison to obese nondiabetic control subjects and patients with subclinical diabetes. Pancreatic insulin secretion rates were measured by deconvolution of peripheral C-peptide over a 24-h period while subjects consumed an isocaloric mixed diet. Subjects were then placed on caloric restriction for at least 6 weeks, during which time body weight fell by at least 10%. Refeeding with solid mixed meals was then resumed for at least 2 weeks until isocaloric intake was attained, and then the meal profiles were repeated. Before weight loss, insulin, C-peptide, and insulin secretion rates were significantly higher in subjects with subclinical diabetes than in the other two groups. Proinsulin concentrations were significantly greater in the two diabetic groups than in control subjects, but, when expressed as a percentage of the total insulin immunoreactivity, the differences were significant only in the group with overt diabetes. Weight loss because of hypocaloric feeding resulted in a significant increase in the rate of clearance of endogenously secreted insulin but did not affect the clearance of C-peptide. In obese subjects and those with subclinical diabetes, weight loss was associated with a reduction in insulin secretion rates, presumably as a result of improvements in insulin sensitivity. In patients with overt diabetes and hyperglycemia, weight loss improved beta-cell responsiveness to glucose and was associated with an increase in insulin clearance and a reduction in proinsulin immunoreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1993

Relative expression of insulin receptor isoforms does not differ in lean, obese, and noninsulin-dependent diabetes mellitus subjects.

The insulin receptor is expressed as two isoforms that differ by a 12-amino acid region at the carboxy-terminus of the alpha-subunit encoded by exon 11. These isoforms are produced by tissue-specific alternate splicing of the insulin receptor mRNA. To determine whether the relative expression of the isoforms is altered in skeletal muscle in two insulin-resistant states, NIDDM and obesity, relative mRNA levels were measured using a polymerase chain reaction technique. There were no differences in the relative amounts of skeletal muscle mRNA encoding the exon 11-containing form compared to the exon 11-lacking form of the insulin receptor among lean normal (30 +/- 2% Ex11-), obese nondiabetic (32 +/- 2%), and NIDDM (31 +/- 1%) subjects. We conclude that altered expression of insulin receptor isoform mRNAs does not account for skeletal muscle insulin resistance in NIDDM and obesity.

Adult↗
PubMed1993

Intracellular glucose metabolism after long term metabolic control with glyburide: improved glucose oxidation with unchanged glycogen synthase activity.

To determine whether improved metabolic control with long term glyburide treatment alters intracellular glucose metabolism independent of effects on glucose uptake (GU), we studied eight obese patients with noninsulin-dependent diabetes mellitus before and 7 months after glyburide therapy. Indirect calorimetry and skeletal muscle biopsies were performed in the basal state and during 300 pmol/m2.min insulin infusions, with glucose turnover rates determined by [3-3H]glucose turnover. During the glucose clamps, rates of GU were matched before and after treatment using equivalent hyperinsulinemia and variable levels of hyperglycemia. After glyburide treatment, rates of GU were decreased in the basal state [4.16 +/- 0.57 vs. 3.29 +/- 0.37 mg/kg fat free mass (FFM)/min; P < 0.05], but similar during glucose clamps (11.53 +/- 1.42 vs. 11.93 +/- 1.32 mg/kg FFM.min; P = NS) according to study design. In both the basal state and during glucose clamps after glyburide therapy, rates of glucose oxidative metabolism (Gox) increased by 68-78% [1.21 +/- 0.16 vs. 2.03 +/- 0.31 mg/kg FFM.min (P < 0.05) and 3.13 +/- 0.51 vs. 5.58 +/- 0.55 mg/kg FFM.min (P < 0.05), respectively], and rates of nonoxidative glucose metabolism decreased [2.96 +/- 0.68 vs. 1.25 +/- 0.21 mg/kg FFM.min (P < 0.05) and 8.40 +/- 1.50 to 6.30 +/- 1.40 mg/kg FFM.min (P < 0.01), respectively]. Circulating plasma FFA levels and rates of fat oxidation (Fox) remained unchanged in both the basal state and during clamp studies. Skeletal muscle glycogen synthase (GS) activity, expressed as fractional velocity, was unchanged by glyburide therapy (2.2 +/- 0.8 vs. 2.7 +/- 0.3% in the basal state and 7.3 +/- 1.8 vs. 6.1 +/- 0.9% during clamps; both P = NS). In summary, at both matched (during clamp studies) and unmatched (during basal studies) rates of GU, improved metabolic control with glyburide therapy resulted in marked improvement of Gox independent of the effects on GU. The improvement in Gox was not associated with changes in Fox, circulating FFA, or muscle GS activity. These data indicate that long term metabolic control achieved by glyburide therapy markedly improves Gox, but not skeletal muscle GS activity, in noninsulin-dependent diabetes mellitus independent of GU and Fox.

Blood Glucose↗
PubMed1993

Intensive conventional insulin therapy for type II diabetes. Metabolic effects during a 6-mo outpatient trial.

OBJECTIVE: To determine whether tight glycemic control can be obtained using intensive conventional split-dose insulin therapy in the outpatient management of type II diabetes without development of unacceptable side effects. RESEARCH DESIGN AND METHODS: Fourteen type II diabetic subjects were treated with an intensive program of conventional insulin (subcutaneous NPH and regular insulin before breakfast and supper) for 6 mo. Insulin dose adjustments were based on an algorithm built on frequent CPG measurements (4-6 times/day). Patients were monitored biweekly as outpatients and admitted 1 day/mo for metabolic evaluation. RESULTS: Glycemic control was achieved by 1 mo (mean plasma glucose fell from 17.5 +/- 0.9 to 7.7 +/- 0.7 mM, P < 0.001) and remained in this range thereafter. Hypoglycemic events at 1 mo were infrequent (mean +/- SE events per patient per month: 4.1 +/- 0.3) and mild in nature, and progressively decreased to 1.3 +/- 0.5 events/mo by 6 mo. After treatment, basal HGO fell 44% from 628 +/- 44 to 350 +/- 17 mumol.m-2.min-1 (P < 0.001), and maximal rates of glucose disposal measured by hyperinsulinemic euglycemic clamp (1800 pmol.m-2.min-1) improved from 1418 +2- 156 to 1657 +/- 128 mumol.m-2.min-1 (P < 0.05). The total dose of exogenous insulin required was 86 +/- 13 U at 1 mo and 100 +/- 24 U at 6 mo. During treatment, mean serum insulin levels increased from 308 +/- 80 to 510 +/- 102 pM (P < 0.05), while body weight increased from 93.5 +/- 5.8 to 102.2 +/- 6.8 kg (P < 0.001). Both pre- and posttreatment glucose disposal rates correlated with the total exogenous insulin dose required to achieve glycemic control (r = -0.75 and -0.78, both P < 0.005). Weight gain was inversely related to the pretreatment glucose disposal rate (r = -0.53, P < 0.05) and directly correlated with both mean day-long serum insulin level (r = 0.67, P < 0.01) and total exogenous insulin dose (r = 0.62, P < 0.02). CONCLUSIONS: Intensive CIT, when combined with CBG measurements, can be used to rapidly improve glycemic control in type II diabetes without development of unacceptable hypoglycemia. This degree of metabolic improvement, however, requires large doses of exogenous insulin to overcome peripheral insulin resistance and results in greater hyperinsulinemia with progressive weight gain.

Algorithms↗
PubMed1992

Sensitivity of the Mini-Mental State Examination to frontal lobe dysfunction in normal aging.

The present study examined the sensitivity of the Mini-Mental State Examination (MMSE) in detecting the frontal lobe dysfunction that occurs with normal aging. Eighty normal, independently living older adults in four age groupings from 50 to 89 were administered the MMSE along with three neurocognitive measures sensitive to frontal lobe functioning. Results revealed age-related cognitive decline on frontal lobe tasks that also was detected by the MMSE. These findings are noteworthy because the MMSE was intended as a measure of gross cognitive status rather than of frontal lobe functioning.

Aged↗
PubMed1992

Role of impaired intracellular glucose metabolism in the insulin resistance of aging.

The insulin resistance of aging is characterized by both reduced glucose uptake and impaired intracellular glucose metabolism. The aim of this study was to determine whether impaired intracellular glucose metabolism contributes to insulin resistance in the elderly independent of reduced glucose uptake. To address this question, glucose uptake in non-obese elderly males was matched to controls using the glucose clamp technique, and intracellular glucose metabolism was assessed in vivo by indirect calorimetry and in vitro by skeletal muscle biopsy for glycogen synthase activity. When elderly subjects were compared with controls at an equivalent basal glucose uptake of approximately 2.5 mg/kg fat-free mass (FFM)/min, muscle glycogen synthase activity was similar (fractional velocity of glycogen synthase at 0.1 mmol/L glucose-6-phosphate [FV0.1], 0.06 +/- 0.1 and 0.07 +/- 0.1), but whole-body rates of glucose oxidation were reduced (1.36 +/- 0.12 v 1.90 +/- 0.11 mg/kg FFM/min, P less than .05). During 40-mU/m2/min hyperinsulinemic clamps at matched rates of glucose uptake (approximately 10.7 mg/kg FFM/min in both groups), glycogen synthase activity was again similar (FV0.1, 0.15 +/- 0.02 and 0.14 +/- 0.02), and glucose oxidation remained reduced in the elderly (4.18 +/- 0.25 v 4.77 +/- 0.17 mg/kg FFM/min, P less than .05). Only during clamps in the maximal range of glucose uptake (approximately 29.5 mg/kg FFM/min) was glucose oxidation between the groups comparable (5.97 +/- 0.50 and 5.75 +/- 0.31 mg/kg FFM/min). Plasma free fatty acid (FFA) concentrations, fat oxidation, and protein oxidation were similar under all study conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Why intraperitoneal delivery of insulin with implantable pumps in NIDDM?

In the normal state, pancreatic secretion of insulin results in a portal/peripheral gradient with the highest concentrations of insulin in the liver. In diabetic patients with absent or insufficient pancreatic insulin secretion who require exogenous insulin, this normal gradient is lost, resulting in numerous abnormalities. This consideration led to interest in the intraperitoneal delivery of insulin, hoping to produce a therapeutic state more closely resembling normal physiology. The development of implantable insulin pumps, which can deliver insulin intraperitoneally, led to numerous studies on insulin-dependent diabetes mellitus (IDDM) patients, demonstrating that insulin delivered intraperitoneally is rapidly and predictably absorbed with most of it going into the portal system, resulting in hepatic delivery of insulin. Studies in IDDM patients have demonstrated that good glucose control can be achieved with intraperitoneal delivery of insulin from implantable pumps with lesser glycemic fluctuations and, therefore, fewer episodes of hypoglycemia. Furthermore, intraperitoneal insulin results in carbohydrate and particularly lipid metabolism that more closely mimics the normal physiological state than produced by injections of insulin. Thus, implantable insulin pumps are being studied for use in IDDM. Many non-insulin-dependent diabetes mellitus (NIDDM) patients have insufficient pancreatic secretion and require exogenous insulin. Because of alterations in hepatic sensitivity to insulin, increments in insulin delivery to the liver may be even more important in NIDDM than IDDM. Furthermore, insulin resistance, which is an integral part of NIDDM, results in higher physiological levels of insulin, which are required for glucose control, and thus significant peripheral hyperinsulinemia occurs in patients receiving exogenous insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1992

Advances in treatment of type II diabetes mellitus in the elderly.

Elderly diabetic patients are prone to the acute and subacute consequences of hyperglycemia, which can adversely affect health, well being, and quality of life. Every elderly patient with diabetes should be offered an individualized treatment plan, consisting of education, dietary counseling, and an exercise program. If fasting and postprandial glucose levels do not stay consistently in the desired range, then an oral hypoglycemic agent should be instituted at the lowest possible dose. When the oral hypoglycemic agent fails, it may be possible to achieve good glycemic control with the addition of insulin. Recent developments in insulin administration can optimize glycemic benefits and reduce potential adverse effects.

Aged↗
PubMed1991

Substrate oxidation errors during combined indirect calorimetry-hyperinsulinemic glucose clamp studies.

The procedure of indirect calorimetry is often combined with the hyperinsulinemic, euglycemic clamp technique so that intracellular rates of glucose oxidation (Gox), fat oxidation (Fox), and energy expenditure (EE) can be determined at different insulin concentrations and rates of whole-body glucose uptake. In order to perform these calculations, rates of protein oxidation (Pox) must be known and are usually estimated from urinary nitrogen (N) excretion. The use of urinary N assumes that this measurement accurately reflects Pox and is unaltered by the glucose clamp technique. To examine these assumptions and determine potential errors in rates of Gox, Fox, and EE with this method, eight healthy subjects each had basal urinary N excretion determined on 4 different days and during a 300 pmol/m2/min hyperinsulinemic, euglycemic clamp. Mean basal urinary N excretion was 6.4 +/- 1.6 mg/min. Within individuals, basal urinary N was highly variable on the 4 different days with a mean coefficient of variation (CV) of 36% +/- 18%. Over the range of basal respiratory quotient (RQ) values in this study (0.78 to 0.85) the day-to-day variation in basal urinary N resulted in potential errors of 11% to 23% for Gox, 16% to 24% for Fox, but minimal effects (less than or equal to 1%) on EE. During the hyperinsulinemic, euglycemic clamp, RQ increased to 0.95 or greater, while urinary N excretion, rather than decreasing as expected, increased by 47% (6.4 +/- 1.6 to 9.4 +/- 2.8 mg/min) due in part to increases in urea clearance from 37.5 +/- 6.7 to 75.2 +/- 12.4 mL/min (P less than .025). This increased urinary N excretion had minimal influence on Fox and EE, but underestimated Gox by up to 5% at RQ less than 0.95. A more accurate estimate of urinary N excretion during hyperinsulinemic clamps may be obtained by correcting for changes in urea clearance. These results indicate that basal urinary N excretion is highly variable and influenced by hyperinsulinemic glucose clamps. Thus, urinary N excretion, particularly during the basal state, may not accurately reflect changes in Pox and can lead to substantial errors in Gox and Fox.

Adult↗
PubMed1991

Current issues in fructose metabolism.

The ingestion of fructose, particularly in refined form, has significantly increased in the North American diet over the last two decades. The unique way in which fructose is metabolized has given rise to much research examining whether fructose is advantageous in appetite control, exercise endurance, and disease states such as diabetes. Overall, there is very little evidence that modest amounts of fructose have detrimental effects on carbohydrate and lipid metabolism in nondiabetic or NIDDM subjects or that its use is particularly advantageous compared to that of other sugars. However, fructose can cause insulin and triglyceride levels to rise dramatically, and hence be potentially harmful, in a subgroup of NIDDM subjects who have concomitant pronounced hypertriglyceridemia. Large doses of fructose should also be avoided by subjects with gout because of the hyperuricemia which may result. No evidence exists that fructose has any clear advantages over glucose in regard to exercise endurance. Similarly there is no conclusive evidence that physiologic amounts of dietary fructose exacerbate copper deficiency or aid in weight control.

Animals↗
PubMed1991

Dose-response characteristics of impaired glucose oxidation in non-insulin-dependent diabetes mellitus.

To determine the dose-response characteristics of impaired glucose oxidation in non-insulin-dependent diabetes mellitus (NIDDM), indirect calorimetry was performed on eight matched control and NIDDM subjects during the basal state and during three glucose clamps at insulin infusion rates of 150, 300, and 1,500 pmol.m-2.min-1. Hyperglycemia was used to achieve matched rates of glucose uptake at each insulin infusion. Glucose uptake in the basal state was greater in NIDDM [3.75 +/- 0.23 vs. 2.50 +/- 0.10 mg.kg fat-free mass (FFM)-1.min-1, P less than 0.005] but was similar at approximately 8, 12, and 26 mg.kg FFM-1.min-1 at each insulin infusion. Basal protein oxidation, fat oxidation, and plasma free fatty acids were similar and equally sensitive to suppression by insulin in both groups. Glucose oxidation was reduced 20-26%, and circulating lactate increased 50-90% at physiological but not at pharmacological insulin concentrations in NIDDM. The dose-response relationship between serum insulin and glucose oxidation was right shifted in NIDDM with half-maximal activation at 368 +/- 91 vs. 179 +/- 27 pM in controls (P less than 0.05). In conclusion, glucose oxidation is reduced at physiological insulin concentrations in NIDDM and cannot be explained by concomitant obesity, increased fat oxidation, or reduced glucose uptake but results from impaired sensitivity to stimulation by insulin, possibly at pyruvate dehydrogenase.

Adult↗
PubMed1991

Multiple defects in muscle glycogen synthase activity contribute to reduced glycogen synthesis in non-insulin dependent diabetes mellitus.

To define the mechanisms of impaired muscle glycogen synthase and reduced glycogen formation in non-insulin dependent diabetes mellitus (NIDDM), glycogen synthase activity was kinetically analyzed during the basal state and three glucose clamp studies (insulin approximately equal to 300, 700, and 33,400 pmol/liter) in eight matched nonobese NIDDM and eight control subjects. Muscle glycogen content was measured in the basal state and following clamps at insulin levels of 33,400 pmol/liter. NIDDM subjects had glucose uptake matched to controls in each clamp by raising serum glucose to 15-20 mmol/liter. The insulin concentration required to half-maximally activate glycogen synthase (ED50) was approximately fourfold greater for NIDDM than control subjects (1,004 +/- 264 vs. 257 +/- 110 pmol/liter, P less than 0.02) but the maximal insulin effect was similar. Total glycogen synthase activity was reduced approximately 38% and glycogen content was approximately 30% lower in NIDDM. A positive correlation was present between glycogen content and glycogen synthase activity (r = 0.51, P less than 0.01). In summary, defects in muscle glycogen synthase activity and reduced glycogen content are present in NIDDM. NIDDM subjects also have less total glycogen synthase activity consistent with reduced functional mass of the enzyme. These findings and the correlation between glycogen synthase activity and glycogen content support the theory that multiple defects in glycogen synthase activity combine to cause reduced glycogen formation in NIDDM.

Diabetes Mellitus, Type 2↗
PubMed1991

In vivo stimulation of the insulin receptor kinase in human skeletal muscle. Correlation with insulin-stimulated glucose disposal during euglycemic clamp studies.

To assess the relationship between insulin receptor (IR) kinase activity and insulin action in vivo in humans, we measured glucose disposal rates (GDR) during a series of euglycemic clamp studies. Simultaneously, we measured IR kinase activity in IRs extracted from skeletal muscle obtained by needle biopsy at the end of each clamp. By preserving the phosphorylation state of the receptors as it existed in vivo at the time of biopsy, we could correlate GDR and IR kinase in skeletal muscle. Eight nondiabetic, nonobese male subjects underwent studies at insulin infusion rates of 0, 40, 120, and 1,200 mU/m2 per min. Kinase activity, determined with receptors immobilized on insulin agarose beads, was measured at 0.5 microM ATP, with 1 mg/ml histone, followed by SDS-PAGE. Insulin increased GDR approximately sevenfold with a half-maximal effect at approximately 100 microU/ml insulin and a maximal effect by approximately 400 microU/ml. Insulin also increased IR kinase activity; the half-maximal effect occurred at approximately 500-600 microU/ml insulin with a maximal 10-fold stimulation over basal. Within the physiologic range of insulin concentrations, GDR increased linearly with kinase activation (P less than 0.0006); at supraphysiologic insulin levels, this relationship became curvilinear. Half-maximal and maximal insulin-stimulated GDR occurred at approximately 20 and approximately 50% maximal kinase activation, respectively. These results are consistent with a role of the kinase in insulin action in vivo. Furthermore, they demonstrate the presence of a large amount of "spare kinase" for glucose disposal.

Adenosine Triphosphate↗
PubMed1991

Analysis of the gene sequences of the insulin receptor and the insulin-sensitive glucose transporter (GLUT-4) in patients with common-type non-insulin-dependent diabetes mellitus.

Insulin resistance is a common feature of non-insulin-dependent diabetes mellitus (NIDDM) and "diabetes susceptibility genes" may be involved in this abnormality. Two potential candidate genes are the insulin receptor (IR) and the insulin-sensitive glucose transporter (GLUT-4). To elucidate whether structural defects in the IR and/or GLUT-4 could be a primary cause of insulin resistance in NIDDM, we have sequenced the entire coding region of the GLUT-4 gene from DNA of six NIDDM patients. Since binding properties of the IRs from NIDDM subjects are normal, we also analyzed the sequence of exons 16-22 (encoding the entire cytoplasmic domain of the IR) of the IR gene from the same six patients. When compared with the normal IR sequence, no difference was found in the predicted amino acid sequence of the IR cytoplasmic domain derived from the NIDDM patients. Sequence analysis of the GLUT-4 gene revealed that one patient was heterozygous for a mutation in which isoleucine (ATC) was substituted for valine (GTC) at position 383. Consequently, the GLUT-4 sequence at position 383 was determined in 24 additional NIDDM patients and 30 nondiabetic controls and all showed only the normal sequence. From these studies, we conclude that the insulin resistance seen in the great majority of subjects with the common form of NIDDM is not due to genetic variation in the coding sequence of the IR beta subunit, nor to any single mutation in the GLUT-4 gene. Possibly, a subpopulation of NIDDM patients exists displaying variation in the GLUT-4 gene.

Aged↗
PubMed1991

Reduced glucose-induced thermogenesis is present in noninsulin-dependent diabetes mellitus without obesity.

Decreased glucose-induced thermogenesis has been observed in all forms of obesity. However, some studies implicate insulin resistance rather than obesity per se as the mechanism by which glucose-induced thermogenesis is reduced. To establish the role of insulin resistance in reduced thermogenesis independent of obesity, we compared energy expenditure in 9 nonobese individuals with noninsulin-dependent diabetes mellitus (NIDDM) to 16 nonobese control subjects using indirect calorimetry and the hyperinsulinemic clamp technique. To document the presence of insulin resistance and reduced glucose-induced thermogenesis in nonobese NIDDM, 6 individuals from each group were studied under identical conditions of hyperinsulinemia (120 mU/m2.min) and euglycemia (approximately 5 mmol/l). Both glucose uptake (0.482 +/- 0.042 vs. 0.737 +/- 0.040 g/min) and energy expenditure above basal (0.04 +/- 0.02 vs. 0.10 +/- 0.02 kcal/min) were decreased in nonobese NIDDM compared to control subjects (both P less than 0.05). To determine whether decreased glucose-induced thermogenesis could be overcome by correcting for reduced glucose uptake, the 9 nonobese NIDDM individuals were age and weight-matched to 9 control subjects and clamps were performed at matched rates of glucose uptake. During a 40 mU/m2.min insulin infusion, the nonobese NIDDM individuals were studied at hyperglycemia (17.5 +/- 1.9 mmol/L) and compared to the control subjects at euglycemia (5.1 +/- 0.1 mmol/L; P less than 0.05). Under these conditions, both groups achieved similar rates of glucose uptake (0.698 +/- 0.040 vs. 0.688 +/- 0.038 g/min, NIDDM and control subjects, respectively) and similar rates of energy expenditure above basal (0.08 +/- 0.03 vs. 0.06 +/- 0.02 kcal/min, P = NS). During 600 mU/m2.min clamps performed at hyperglycemia (19.0 +/- 1.2 vs. 14.5 +/- 1.1 mmol/L, NIDDM vs. control subjects, respectively; P less than 0.05), rates of maximal glucose uptake (1.538 +/- 0.093 vs. 1.518 +/- 0.047 g/min) and energy expenditure above basal (0.34 +/- 0.03 vs. 0.31 +/- 0.03 kcal/min) were also similar (P = NS). In conclusion nonobese NIDDM is associated with both decreased rates of glucose uptake and decreased glucose-induced thermogenesis. Decreased glucose substrate availability, due to impaired insulin action, appears to be the critical determinant of glucose-induced thermogenesis in nonobese NIDDM. These data indicate that decreased thermogenesis in NIDDM is a consequence of insulin resistance and can occur independent of obesity.

Body Temperature Regulation↗