Biomedical subjects

T Jenssen

Publications and source records attributed to T Jenssen.

At least 37 records · Page 2Linked to original sources

PubMed1998

Insulin kinetics, insulin action, and muscle morphology in lean or slightly overweight persons with impaired glucose tolerance.

Glucose intolerance is influenced by body fat mass, as well as muscle fiber composition. To examine the relation between the metabolic profile and muscle morphology in this condition, we performed muscle biopsies and hyperglycemic clamps to determine insulin secretion and clearance, and the insulin effects on glucose disposal and nonesterified fatty acids (NEFA) in 45 glucose intolerant persons (body mass index [BMI], 27.8 +/- 3.0 kg/m2) and 45 normoglycemic controls (BMI, 25.8 +/- 2.7 kg/m2) (P = .001). After adjustment for BMI, glucose-intolerant subjects had lower first-phase insulin release (726 v 954 pmol/L, P = .04). Glucose-intolerant subjects and controls differed in fasting insulin, insulin clearance, and insulin sensitivity to glucose disposal before, but not after, standardizing for BMI. During the clamp, glucose-intolerant subjects had less NEFA suppression and elevated levels of NEFA compared with controls (85% +/- 9% v 90% +/- 6%, P = .02; and 70 +/- 42 micromol/L v 45 +/- 28 micromol/L, P = .01). Glucose-intolerant subjects also had a higher percentage of insulin-insensitive, type 2b muscle fibers, which are not adapted for fat oxidation (7% +/- 9% v 9% +/- 9%, P = .003). BMI was not associated with NEFA suppression or the percentage of type 2b muscle fibers in either group. In conclusion, glucose-intolerant persons have impaired first-phase insulin release, an elevated percentage of type 2b muscle fibers, and increased NEFA availability. Reduced insulin clearance, hyperinsulinemia, and insulin resistance were associated with small increments in BMI.

Body Mass Index↗

PubMed1998

Insulin resistance in hypertension is associated with body fat rather than blood pressure.

The insulin resistance syndrome has been characterized by hypertension, upper body obesity, insulin resistance, hyperinsulinemia, glucose intolerance, and hypertriglyceridemia. Previous studies are inconsistent regarding the relationship between blood pressure and insulin resistance. We therefore compared the metabolic profile in 60 hypertensive subjects (mean+/-SD arterial pressure, 116+/-7 mm Hg) and 60 normotensive subjects (mean arterial pressure, 88+/-5 mm Hg) matched for age, gender, and body mass index. Hypertensives had significantly higher waist-to-hip ratio than normotensives (P=0.002). The groups did not differ in fasting plasma glucose (0.2 mmol/L, P=0.09), insulin (6 pmol/L, P=0.14), insulin sensitivity index (-0.01 micromol x kg(-1) x min(-1) x pmol/L(-1), P=0.7), and suppression of nonesterified fatty acids during a hyperglycemic clamp (1%, P=0.40). There were significant differences in fasting levels of C-peptide (50 pmol/L, P=0.004) and proinsulin (2 pmol/L, P=0.01), 2-hour postload levels of glucose (0.8 mmol/L, P=0.01) and insulin (84 pmol/L, P=0.01) after oral glucose challenge, and hepatic glucose production during the clamp (2.87 micromol x kg(-1) x min(-1), P=0.02). These differences were not significant when controlling for waist-to-hip ratio. Body mass index and waist-to-hip ratio were similarly associated with the insulin sensitivity index in the hypertensive (r=-0.59, P=0.0001 and r=-0.32, P=0.05) and normotensive (r=-0.58, P=0.0001 and r=-0.39, P=0.05) groups. Hypertension per se is not associated with insulin resistance. However, even small increments in both body mass index and waist-to-hip ratio, as often seen in hypertension, may lead to impairment in insulin sensitivity, probably mediated through altered lipid metabolism.

Adipose Tissue↗

PubMed1997

Gender differences in the relationships between plasma plasminogen activator inhibitor-1 activity and factors linked to the insulin resistance syndrome in essential hypertension.

Impaired fibrinolysis due to elevated levels of plasma plasminogen activator inhibitor type 1 (PAI-1) is a risk factor for thromboembolic disease. Hypertension, obesity, derangements in lipid and glucose homeostasis, and elevated levels of PAI-1 are features of the insulin resistance syndrome. The interrelationships between PAI-1 and the metabolic disturbances seen in this condition are unsettled. We investigated the associations between PAI-1 activity and components of the insulin resistance syndrome in 53 men and 31 women with untreated hypertension. In men, PAI-1 activity correlated significantly with plasma glucose (r = .41, P = .002), insulin sensitivity (r = -.35, P = .01), and insulin-induced suppression of nonesterified fatty acid (NEFA) (r = -.43, P = .007). Plasma glucose and NEFA suppression were independently associated with PAI-1 activity in a multivariate analysis. In women, PAI-1 activity correlated with body mass index (r = .62, P = .0005), waist-to-hip ratio (r = .75, P = .0001), plasma glucose (r = .50, P = .007), insulin (r = .49, P = .009), proinsulin (r = .57, P = .002), C-peptide (r = .60, P = .0009), insulin sensitivity (r = -.74, P = .0001), NEFA suppression (r = -.64, P = .003), and triglycerides (r = .58, P = .001). In multivariate analyses, insulin sensitivity and NEFA suppression were independently associated with PAI-1 if waist-to-hip ratio was not included in the model. After introduction of waist-to-hip ratio into the model, waist-to-hip ratio was the only independent predictor of PAI-1 activity. We conclude that in women, waist-to-hip ratio, body mass index, and insulin-induced NEFA suppression are determinants for PAI-1 activity. In men, insulin-induced NEFA suppression and plasma glucose are independently associated with PAI-1 activity.

Adult↗

PubMed1997

Fibrinolytic function after dietary supplementation with omega3 polyunsaturated fatty acids.

Hypertension is associated with derangements in glucose and lipid metabolism. Increased levels of plasminogen activator inhibitor type 1 (PAI-1) are thought to potentiate the development of coronary events in this condition. Fish oil (omega3 polyunsaturated fatty acids [PUFAs]) have lipid-lowering effects, but the cardioprotective potential has been questioned because fish oil has been found to increase PAI-1 activity. This study was performed to determine the effects of omega3 PUFAs on the fibrinolytic function in hypertension. Seventy-eight persons with untreated hypertension were included in a 16-week, double-blind, randomized, controlled intervention study with 4 g/d of eicosapentaenoic and docosahexaenoic acids or corn oil placebo. Plasma PAI-1 activity, tissue plasminogen activator (tPA) activity, levels of fibrinogen and factor VII(c), and platelet count were measured before and after intervention (mean+/-SE). PAI-1 activity changed similarly in the fish oil and corn oil groups (1.8+/-1.0 U/mL versus 3.5+/-1.2 U/mL, P=.25), as did tPA (-0.02+/-0.02 IU/mL versus -0.13+/-0.03 IU/mL, P=.28), levels of factor VII(c) (6+/-5% versus 5+/-4%, P>.3), and platelet count (2+/-7x10(9)/L versus 3+/-5x10(9)/L, P>.3). None of these variables changed from pretreatment levels during fish oil intake. Fibrinogen levels increased significantly both during fish oil (0.6+/-0.1 g/L, P=.0001) and corn oil (0.4+/-0.1 g/L, P=.002) intake. There was no between-group difference (P>.3). In conclusion, a daily intake of 4 g omega3 PUFAs does not affect PAI-1 and tPA activity in persons with hypertension. A modest increase in fibrinogen levels was observed after both fish oil and corn oil intake.

Adult↗

PubMed1996

Glutamine and alanine metabolism in NIDDM.

Gluconeogenesis is increased in NIDDM. We therefore examined the metabolism of glutamine and alanine, the most important gluconeogenic amino acids, in 14 postabsorptive NIDDM subjects and 18 nondiabetic volunteers using a combination of isotopic ([6-3H]glucose (20 microCi, 0.2 microCi/min), [U-14C]glutamine (20 microCi, 0.2 microCi/min), [3-13C]alanine (99% 13C, 2 mmol, 20 micromol/min), [ring-2H5]phenylalanine (99% 2H, 2 micromol/kg, 0.03 micromol x kg(-1) x min(-1)), and limb balance techniques. Alanine turnover (4.54 +/- 0.24 vs. 5.64 +/- 0.33 micromol x kg(-1) x min(-1)), de novo synthesis (3.00 +/- 0.25 vs. 4.01 +/- 0.33 micromol x kg(-1) x min(-1)), and conversion to glucose (1.02 +/- 0.09 vs. 1.56 +/- 0.17 micromol x kg(-1) x min(-1)) were increased in NIDDM subjects (all P < 0.01), while its forearm release (0.45 +/- 0.04 vs. 0.39 +/- 0.04 micromol x kg(-1) x min(-1)) was unaltered. Although glutamine turnover (4.81 +/- 0.23 vs. 4.40 +/- 0.31 micromol x kg(-1) x min(-1)) was unaltered in NIDDM, its conversion to glucose (0.57 +/- 0.04 vs. 1.08 +/- 0.10 micromol x kg(-1) x min(-1)) and to alanine (0.10 +/- 0.01 vs. 0.34 +/- 0.04 micromol x kg(-1) x min(-1)) (both P = 0.001) was increased while its oxidation (2.84 +/- 0.27 vs. 1.84 +/- 0.15 micromol x kg(-1) x min(-1), P = 0.03) and forearm release (0.77 +/- 0.05 vs. 0.62 +/- 0.09 micromol x kg(-1) x min(-1), P < 0.008) were both reduced. Our results thus demonstrate that there are substantial alterations of glutamine and alanine metabolism in NIDDM. Conversion of both amino acids to glucose and the proportion of their turnover used for gluconeogenesis are increased; release of both amino acids from tissues other than skeletal muscle seems to be increased. Finally, the reduction in glutamine oxidation, possibly the result of competition with glucose and free fatty acids as fuels, makes more glutamine available for gluconeogenesis without a change in its turnover.

Alanine↗

PubMed1995

Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial.

OBJECTIVE: To determine whether dietary supplementation with fish oil adversely affects glycemic control in patients with hypertension. DESIGN: Randomized, double-blind, placebo-controlled study. PATIENTS: 78 persons with untreated hypertension recruited from a population survey. INTERVENTION: Participants were randomly assigned to receive eicosapentaenoic and docosahexaenoic acids, 4 g/d, or corn oil placebo, 4 g/d, for 16 weeks. MEASUREMENTS: An oral glucose tolerance test; assessments of insulin release, glucose disposal, and insulin sensitivity done using the hyperglycemic clamp technique to keep plasma glucose levels at 10 mmol/L for 180 minutes; assessment of insulin sensitivity done using a euglycemic hyperinsulinemic clamp technique (infusing insulin and glucose to keep plasma glucose levels at 5 mmol/L); assessments of lipid levels and blood pressure. Measurements were done before and after intervention. RESULTS: Changes in integrated glucose and insulin response after the oral glucose challenge did not differ between the fish oil and corn oil groups after intervention (-0.6 +/- 0.7 compared with -1.0 +/- 0.6 mmol/L [P > 0.3] for integrated glucose and 143 +/- 76 compared with 169 +/- 84 pmol/L [P > 0.3] for insulin response). Changes in first-phase insulin release (34 +/- 72 pmol/L in the fish oil group compared with 191 +/- 112 pmol/L in the corn oil group [P > 0.3]), second-phase insulin release (179 +/- 66 pmol/L compared with 257 +/- 122 pmol/L [P > 0.3]), and insulin sensitivity index (-0.03 +/- 0.01 compared with -0.01 +/- 0.01 [mumol/kg.min divided by pmol/L]; P > 0.3) were also similar in both groups after treatment. Fish oil lowered systolic blood pressure by 3.8 mm Hg more than control (P = 0.04) and lowered diastolic blood pressure by 2.0 mm Hg more than control (P = 0.10). After fish oil treatment, triglyceride levels decreased by 0.28 +/- 0.08 mmol/L more than control (P = 0.01), and very-low-density lipoprotein cholesterol levels decreased by 0.13 +/- 0.04 mmol/L more than control (P = 0.01). CONCLUSION: Fish oil, in doses that reduce blood pressure and lipid levels in hypertensive persons, does not adversely affect glucose metabolism.

Adult↗

PubMed1995

Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM. Evidence from studies in normal glucose-tolerant individuals with a first-degree NIDDM relative.

OBJECTIVE: To test the hypothesis that insulin resistance precedes impaired insulin secretion in individuals genetically predisposed to non-insulin-dependent diabetes mellitus (NIDDM). DESIGN: Case-control study. SETTING: Outpatient facility of clinical research center. PARTICIPANTS: One hundred volunteers of European ancestry having normal glucose tolerance, 50 with and 50 without a first-degree NIDDM relative, matched for age, sex, and degree of obesity. MAIN OUTCOME MEASURES: Insulin secretion and insulin sensitivity assessed by hyperglycemic (N = 100) and euglycemic-hyperinsulinemic (N = 62) clamp experiments. RESULTS: The individuals with a first-degree NIDDM relative had reduced first- and second-phase insulin responses (mean +/- SEM, 939 +/- 68 vs 1209 +/- 82 pmol/L, and 322 +/- 19 vs 407 +/- 24 pmol/L, respectively, P = .001 and .01), but their insulin sensitivity (148 +/- 6 and 92 +/- 6 nmol.kg-1.min-1/pmol.L-1 in hyperglycemic and euglycemic clamp studies) did not differ from that of the control group (126 +/- 5 and 81 +/- 7 nmol.kg-1.min-1/pmol.L-1, in hyperglycemic and euglycemic clamp studies, P = .07 and .24, respectively). In some individuals only first- or only second-phase insulin responses were reduced. CONCLUSION: In this study population, heterogeneous defects in insulin secretion were demonstrated, while defects in insulin sensitivity were not evident. We therefore conclude that since the earliest defects identified in a group genetically at high risk to develop NIDDM are those related to insulin secretion, defects in insulin secretion rather than insulin sensitivity are likely the major genetic factor predisposing to development of NIDDM.

Adult↗

PubMed1995

Estimation of glucose-alanine-lactate-glutamine cycles in postabsorptive humans: role of skeletal muscle.

To evaluate transfer of carbon between plasma glucose and plasma alanine (glucose-alanine cycle) and lactate (Cori cycle), to assess the contribution of skeletal muscle to these cycles, and to determine whether a glucose-glutamine cycle exists in postabsorptive humans, we infused 11 normal overnight-fasted volunteers with [2-3H]glucose, [6-14C]glucose, and [3-13C]alanine to isotopic steady state and in 7 of these simultaneously measured forearm net balance, uptake, and release of labeled and unlabeled glucose, lactate, and alanine. We found that 40.9 +/- 3.3, 66.8 +/- 3.2, and 13.4 +/- 1.1%, respectively, of plasma alanine, lactate, and glutamine carbon came from plasma glucose. More plasma glucose was converted to plasma alanine than could be derived from plasma alanine (1.89 +/- 0.20 vs. 1.48 +/- 0.15 mumol.kg-1.min-1, P < 0.001). A similar direction of net carbon flux was found for lactate (8.5 vs. 4.2 mumol.kg-1.min-1), with only glutamine adding more carbon to plasma glucose than was received from it (1.0 vs. 0.75 mumol.kg-1.min-1). Skeletal muscle accounted for 50.2 +/- 3.9 and 45.5 +/- 5.7% of the overall appearance of alanine and lactate in plasma and 54.2 +/- 5.4 and 36.4 +/- 4.2% of their respective origins from plasma glucose. Skeletal muscle release of alanine and lactate that had been formed from plasma glucose accounted for 19.1 +/- 2.1 and 48.4 +/- 4.8%, respectively, of muscle glucose uptake and 42.4 +/- 5.5 and 49.9 +/- 5.8% of the overall release of alanine and lactate from muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Inhibitor-stimulated non-parallel pancreatic secretion in man: hormonal and neural regulation?

BACKGROUND: We wanted to study whether a total inhibition of tryptic activity in the duodenum would induce a cholecystokinin (CCK)-dependent increase in pancreatic exocrine proteinase secretion. METHODS: Concentrations of CCK and activities and concentrations of pancreatic enzymes were measured in human plasma and duodenal juices, respectively, collected during continuous intraduodenal instillations of proteinase inhibitors, with and without intravenous atropine administration. RESULTS: Inhibitor instillation totally abolished tryptic activity and reduced the chymotryptic and elastase (1 and 2) activities by 95-100%. The inhibitors caused a rapid increase in the concentrations of trypsin, chymotrypsin, and pancreatic secretory trypsin inhibitor (PSTI) but had only a slight or no effect on amylase and elastase 1 secretion. An enhanced secretion of PSTI lends support to a possible connection between PSTI (resembling the monitor peptide causing CCK release in rats) and the enzyme secretion in man. CCK increased from 7 to 12-13 pmol/l. Intravenous atropine almost completely blocked the inhibitor-stimulated enzyme and PSTI secretion and reduced amylase activity by 50%. A further significant (P = 0.002) increase in the inhibitor-induced CCK output was found during atropine administration, as compared with the test situation without atropine. CONCLUSION: The inhibitor-induced pancreatic secretion during total inhibition of tryptic activity shows a non-parallel secretion requiring different signals for different enzymes. The increase in plasma CCK levels indicates that CCK is feedback-regulated by both an inhibitor-mediated decrease in duodenal enzyme activity and a further decrease in pancreatic enzyme secretion by atropine.

Atropine↗

PubMed1995

Effects of naloxone on glucagon and insulin concentrations after injection of endotoxin in rats.

OBJECTIVE: To find out how infusions of endotoxin and endotoxin plus naloxone affected glucose, glucagon, and insulin concentrations in rats. DESIGN: Random control study. SETTING: University hospital, Norway. MATERIAL: 27 Male Wistar rats. INTERVENTIONS: 8 Rats were given Escherichia coli endotoxin 0.25 mg in saline; 5 were given a naloxone infusion (0.4 ml of 0.04 mg/ml for the first half hour and continued at a rate of 0.4 ml/hour for a total of 80 minutes) starting 10 minutes before the same dose of endotoxin; 6 were given saline alone for 70 minutes, and 8 saline alone for 10 minutes. Blood was taken for analysis after 70 minutes in the first three groups and at the end of the infusion in the 10 minute group. MAIN OUTCOME MEASURES: Serum concentrations of glucose, glucagon, and insulin compared with baseline (10 min group). RESULTS: Median (interquartile) concentrations of all three substances rose significantly 70 minutes after the injection of endotoxin compared to basal values: 9.8 (8.2-10.9) compared with 6.0 (4.8-7.5) mmol/l for glucose (p < 0.01); 53.1 (44.6-56.0) compared with 3.6 (3.1-5.1) ng/l for glucagon; and 39.4 (38-50.4) compared with 16.7 (11.2-25.5) pmol/l for insulin. When naloxone was combined with endotoxin glucagon and insulin concentrations were significantly lower: 24.3 (23.9-37.5) ng/l (p < 0.01), and 30.6 (24.5-31.6 pmol/l (p < 0.05), respectively. The concentration of glucose in venous blood was unchanged. CONCLUSIONS: The rise in glucagon and insulin concentrations after endotoxin infusions may be partly mediated by opioids. Naloxone in the dose given did not abolish the increase in glucagon after endotoxin. The high glucagon:insulin ratio after both endotoxin alone and endotoxin plus naloxone may be important in the aetiology of the hyperglycaemia seen.

Animals↗

PubMed1993

Dose-response effects of lactate infusions on gluconeogenesis from lactate in normal man.

Lactate is the predominant gluconeogenic precursor in man. To determine the dose-response relationships between plasma lactate concentration and rates of lactate incorporation in plasma glucose (lactate gluconeogenesis, LGN), we infused 17 normal volunteers with sodium lactate for 180 min at rates ranging from 6 to 40 mumol kg-1 min-1 and measured [U-14C]lactate incorporation into plasma glucose, as well as rates of lactate and glucose appearance in plasma. With the highest lactate infusions, plasma lactate increased up to 7 mM (compared to 1.1 +/- 0.13 mM during control sodium bicarbonate infusions, n = 10) and LGN averaged 4.73 +/- 0.23 mumol kg-1 min-1 (compared to 1.57 +/- 0.26 mumol kg-1 min-1 in bicarbonate control experiments, P < 0.001). The data relating plasma lactate concentration to LGN best fit a sigmoidal curve which plateaued at plasma lactate concentrations of approximately 6 mM and yielded an ED50 of 2.04 +/- 0.20 (SD) mM and a Vmax (6.25 +/- 1.2) (SD) (mumol kg-1 min-1). The sum of the basal rate of lactate appearance and the rate of lactate infusion was not significantly different from the overall rates of lactate appearance during the lactate infusions (35.8 +/- 2.2 vs. 34.8 +/- 2.9 mumol kg-1 min-1, P = 0.23). Thus, our results support the view that infusion of exogenous lactate does not suppress endogenous lactate appearance in plasma.

Adult↗

PubMed1992

[Treatment of non-insulin dependent diabetes (type 2 diabetes mellitus)].

Type 2 diabetes mellitus is characterized by impaired insulin release and sensitivity, elevated blood sugar and unfavourable changes in blood lipids. Insulin resistance and adverse blood lipids are also seen in the state of essential hypertension (the metabolic syndrome). Patients should learn to measure their own blood sugar. Treatment usually begins with regulation of the diet for 3-6 months. If this treatment fails, the next step is to give oral antidiabetic agents. Insulin treatment is required 1) when blood sugar is excessively high; 2) when oral agents fail; and 3) in case of increased need of insulin due to intercurrent disease. Antihypertensive treatment should not have adverse metabolic effects in patients with type 2 diabetes.

Blood Glucose Self-Monitoring↗

PubMed1992

Evidence against the hypothesis that hyperinsulinemia increases sympathetic nervous system activity in man.

To test the hypothesis that physiologic hyperinsulinemia activates the sympathetic nervous system in humans, we measured changes in plasma norepinephrine as well as epinephrine concentrations during euglycemic hyperinsulinemic clamp experiments in which normal volunteers were infused with insulin for up to 12 hours, at rates chosen to simulate the basal and postprandial hyperinsulinemia seen in insulin-resistant states. Infusions of insulin increased plasma insulin threefold (to approximately 200 pmol/L) and 15-fold (to approximately 1,000 pmol/L) in simulations of fasting and postprandial hyperinsulinemia. In neither experiment did plasma norepinephrine or epinephrine change significantly. In control experiments in which saline was infused for 12 hours, plasma epinephrine increased twofold (P less than .05), but plasma norepinephrine did not change. Therefore, we conclude that hyperinsulinemia of the magnitude seen in the insulin-resistant humans does not increase sympathetic nervous system activity.

Adult↗

PubMed1992

Simultaneous assessment of insulin secretion and insulin sensitivity using a hyperglycemia clamp.

A hyperglycemic clamp is an established method to assess insulin secretion and is generally used only for this purpose. To determine whether it could also be used to assess insulin sensitivity, we compared insulin sensitivity indices (ISI) obtained during euglycemic and hyperglycemic clamp experiments in 22 nonobese volunteers (body mass index, 23.9 +/- 0.6 kg/m2) and in 20 obese individuals (body mass index, 30.8 +/- 1.3 kg/m2) matched for age and gender. The ISI values (micromoles per kg.min/pmol) of the obese group assessed during hyperglycemic (0.088 +/- 0.011) and euglycemic (0.050 +/- 0.005) clamp experiments were both significantly lower than the ISI of the nonobese group assessed in hyperglycemic and euglycemic clamp experiments (0.179 +/- 0.024 and 0.096 +/- 0.009, respectively; both P less than 0.01). Although the ISI values obtained with hyperglycemic clamps were consistently greater than those obtained with euglycemic clamp (0.137 +/- 0.016 vs. 0.075 +/- 0.007; P less than 0.001), they were highly correlated (r = 0.84; P less than 0.0001). Moreover, when these indices were converted to clearance rates, thereby correcting for the mass action effects of glucose on glucose disposal, the values obtained with the hyperglycemic clamp (0.0137 +/- 0.0016 mL/kg.min/pmol) were statistically identical to those obtained with the euglycemic clamp (0.0142 +/- 0.0013 mL/kg.min/pmol), as indicated by a regression equation having an intercept of 0 and a slope (1.03) not different from 1. We, therefore, conclude that the hyperglycemic clamp and the euglycemic clamp yield comparable estimates of insulin sensitivity and that, under appropriate conditions, the hyperglycemic clamp technique may be used to assess both insulin sensitivity and insulin secretion in the same individual in a single experiment.

Blood Glucose↗

PubMed1991

Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction.

To define glycemic thresholds for activation of counterregulatory hormone secretion, initiation of symptoms (autonomic and neuroglycopenic), and onset of deterioration of cognitive function, we measured indexes of these responses during glycemic plateaus of 90, 78, 66, 54, and 42 mg/dl in 10 normal volunteers, with the use of the hyperinsulinemic glucose clamp technique. Activation of glucagon, epinephrine, norepinephrine, and growth hormone secretion began at arterialized venous plasma glucose concentrations of 68 +/- 1, 68 +/- 1, 65 +/- 1, and 67 +/- 2 (SE) mg/dl, respectively. Autonomic symptoms (anxiety, palpitations, sweating, irritability, and tremor) began at 58 +/- 2 mg/dl, which was significantly (P = 0.0001) lower. Neuroglycopenic symptoms (hunger, dizziness, tingling, blurred vision, difficulty thinking, and faintness) and deterioration in cognitive function tests began at 51 +/- 3 and 49 +/- 2 mg/dl, respectively, values that were both significantly (P = 0.018 and 0.004, respectively) lower than that for initiation of autonomic symptoms. We therefore conclude that there is a distinct hierarchy of responses to decrements in plasma glucose, such that the threshold for activation of counterregulatory hormone secretion occurs at higher plasma glucose levels than that for initiation of autonomic warning symptoms, which in turn occurs at higher plasma glucose levels than that for onset of neuroglycopenic symptoms and deterioration in cerebral function. Such a hierarchy would maximize the opportunity to avoid incapacitating hypoglycemia.

Adult↗

PubMed1990

[The need of special services in the future care of the mentally retarded].

A proposal for deinstitutionalization of the mentally retarded in Norway passed the Norwegian Storting in May 1988. The Ministry of Health and Social Affairs has prepared guidelines for planning and implenting this reform. On 1 January 1991 the responsibility for providing the necessary services was transferred to the municipalities. Many problems have to be solved in order to ensure that the life of each mentally retarded person is qualitatively improved after normalization and integration into society. In July 1989 the Ministry of Health and Social Affairs issued a document which assumed that necessary specialists and special services for the mentally retarded already exist, and are being used. Our study has questioned this assumption as being incorrect or incomplete. We interviewed persons in charge of the system of health care in all 19 Norwegian counties. Our conclusions are as follows: The mentally retarded do receive specialist services in various areas of somatic medicine. Their needs as regards psychiatric care are not taken care of by psychiatric specialists in hospitals or at out-patient facilities. Data shows that the system of institutionalized health care for the mentally retarded provides unique services which are best described as systematically applied behaviour analyses. Such special competence is often lacking in the Norwegian health services otherwise. In order to ensure that the mentally retarded will receive the best possible care, this competence must be integrated into the future system of care. It is most importance to consider these problems without delay. This article also discusses organizing special training and treatment for the mentally retarded themselves and special training for the persons providing the care.

Health Planning Guidelines↗

PubMed1990

Failure of substrate-induced gluconeogenesis to increase overall glucose appearance in normal humans. Demonstration of hepatic autoregulation without a change in plasma glucose concentration.

It has been proposed that increased supply of gluconeogenic precursors may be largely responsible for the increased gluconeogenesis which contributes to fasting hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM). Therefore, to test the hypothesis that an increase in gluconeogenic substrate supply per se could increase hepatic glucose output sufficiently to cause fasting hyperglycemia, we infused normal volunteers with sodium lactate at a rate approximately double the rate of appearance observed in NIDDM while clamping plasma insulin, glucagon, and growth hormone at basal levels. In control experiments, sodium bicarbonate was infused instead of sodium lactate at equimolar rates. In both experiments, [6-3H]-glucose was infused to measure glucose appearance and either [U-14C]lactate or [U-14C]alanine was infused to measure the rates of appearance and conversion of these substrates into plasma glucose. Plasma insulin, glucagon, growth hormone, C-peptide, and glycerol concentrations, and blood bicarbonate and pH in control and lactate infusion experiments were not significantly different. Infusion of lactate increased plasma lactate and alanine to 4.48 +/- 3 mM and 610 +/- 33 microM, respectively, from baseline values of 1.6 +/- 0.2 mM and 431 +/- 28 microM, both P less than 0.01; lactate and alanine rates of appearance increased to 38 +/- 1.0 and 8.0 +/- 0.3 mumol/kg per min (P less than 0.01 versus basal rates of 14.4 +/- 0.4 and 5.0 +/- 0.5 mumol/kg per min, respectively). With correction for Krebs cycle carbon exchange, lactate incorporation into plasma glucose increased nearly threefold to 10.4 mumol/kg per min and accounted for about 50% of overall glucose appearance. Alanine incorporation into plasma glucose increased more than twofold. Despite this marked increase in gluconeogenesis, neither overall hepatic glucose output nor plasma glucose increased and each was not significantly different from values observed in control experiments (10.8 +/- 0.5 vs. 10.8 +/- 0.5 mumol/kg per min and 5.4 +/- 0.4 vs. 5.3 +/- 0.3 mM, respectively). We, therefore, conclude that in normal humans there is an autoregulatory process independent of changes in plasma glucose and glucoregulatory hormone concentrations which prevents a substrate-induced increase in gluconeogenesis from increasing overall hepatic glucose output; since this process cannot be explained on the basis of inhibition of gluconeogenesis from other substrates, it probably involves diminution of glycogenolysis. A defect in this process could explain at least in part the increased hepatic glucose output found in NIDDM.

Alanine↗

PubMed1990

Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM.

To assess the role of muscle and liver in the pathogenesis of postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM), we administered an oral glucose load enriched with [14C]glucose to 10 NIDDM subjects and 10 age- and weight-matched nondiabetic volunteers and compared muscle glucose disposal by measuring forearm balance of glucose, lactate, alanine, O2, and CO2 (with forearm calorimetry). In addition, we used the dual-lable isotope method to compare overall rates of glucose appearance (Ra) and disappearance (Rd), suppression of endogenous glucose output, and splanchnic glucose sequestration. During the initial 1-1.5 h after glucose ingestion, plasma glucose increased by approximately 8 mM in NIDDM vs. approximately 3 mM in nondiabetic subjects (P less than 0.01); overall glucose Ra was nearly 11 g greater in NIDDM than nondiabetic subjects (45.1 +/- 2.3 vs. 34.4 +/- 1.5 g, P less than 0.01), but glucose Rd was not significantly different in NIDDM (35.1 +/- 2.4 g) and nondiabetic (33.3 +/- 2.7 g) subjects. The greater overall glucose Ra of NIDDM subjects was due to 6.8 g greater endogenous glucose output (13.7 +/- 1.1 vs. 6.8 +/- 1.0 g, P less than 0.01) and 3.8 g less oral glucose splanchnic sequestration of the oral load (31.4 +/- 1.5 vs. 27.5 +/- 0.9 g, P less than 0.05). Although glucose taken up by muscle was not significantly different in NIDDM and nondiabetic subjects (39.3 +/- 3.5 vs. 41.0 +/- 2.5 g/5 h), a greater amount of the glucose taken up by muscle in NIDDM was released as lactate and alanine (11.7 +/- 1.0 vs. 5.2 +/- 0.3 g in nondiabetic subjects, P less than 0.01), and less was stored (11.7 +/- 1.3 vs. 16.9 +/- 1.5 g, P less than 0.05). We conclude that increased systemic glucose delivery, due primarily to reduced suppression of endogenous hepatic glucose output and, to a lesser extent, reduced splanchnic glucose sequestration, is the predominant factor responsible for postprandial hyperglycemia in NIDDM.

Administration, Oral↗