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Kinetics and metabolic activity of biosynthetic NPH insulin evaluated by the glucose clamp technique.

The glucose clamp technique has been used to evaluate the metabolic activity of NPH biosynthetic insulin in diabetic subjects free from anti-insulin antibodies. After overnight blood glucose normalization with a glucose-controlled insulin infusion system (Biostator), an s.c. injection of NPH insulin was given in the abdominal region. The insulin dose (0.236 +/- 0.05 U/kg body wt) was related to the usual intermediate-acting insulin requirement in the morning. Glucose was clamped at 100 mg/dl by a feedback i.v. glucose infusion. The end of the action of s.c. injected insulin considered conventionally to be the time of the spontaneous rise of blood glucose to 110 mg/dl. Free insulin levels were higher and the length of action was longer after NPH porcine than after NPH biosynthetic human insulin (BHI) (area under the free insulin curve: porcine 1423 +/- 556 mU/L/h; BHI 1045 +/- 338 mU/L/h, P less than 0.05; length of action: porcine 16.0 +/- 3.2 h; BHI 13.7 +/- 0.9 h, P less than 0.05); the glucose requirement was higher after porcine (76.8 +/- 13.5 g) than after BHI (58.5 +/- 14.6 g) without reaching statistical significance. However, the metabolic activity of the bioavailable insulin (index of plasma free insulin activity) was similar for the two insulins (porcine 381 +/- 77.4, BHI 342.8 +/- 54.2 mU/L/g of glucose/h). We conclude that a difference in pharmacokinetics exists between NPH BHI and porcine NPH insulin, which makes the latter metabolically more active. The different behavior does not seem to be related to the insulin molecule itself but could be a consequence of the unequal content of protamine in the two pharmacologic preparations.

Adult↗

Alimentary hyperglycemia in patients with subtotal gastrectomy is associated with decreased insulin secretion but not with insulin resistance.

BACKGROUND: It is not clear whether alimentary hyperglycemia in gastrectomized patients is related with glucose tolerance or not. METHODS: Glucose tolerance, insulin secretion, and peripheral insulin sensitivity were evaluated in 36 patients who underwent subtotal gastrectomy for gastric cancer using the oral glucose tolerance test (OGTT), the intravenous glucose tolerance test (IVGTT) and the euglycemic hyperinsulinemic glucose clamp technique (Glucose clamp). RESULTS: Patients were categorized into three groups by OGTT; 8 cases were in group I (normal), 19 cases in group II (alimentary hyperglycemia), and 9 cases in group III (glucose intolerance). Both glucose disappearance rate (K value expressed as, %/min) and insulinogenic index as determined by IVGTT were significantly lower in groups II (1.00 +/- 0.24, 0.21 +/- 0.18, respectively) and III (0.90 +/- 0.13, 0.11 +/- 0.14, respectively), compared with group I (1.58 +/- 0.71, 0.35 +/- 0.18, respectively). Peripheral insulin sensitivity as measured by glucose clamp was not decreased in groups II and III. CONCLUSIONS: These results suggest that in patients with alimentary hyperglycemia, glucose tolerance was impaired due to a decreased pancreatic sensitivity to blood glucose and not due to insulin resistance.

Aged↗

Insulin sensitivity relates to other cardiovascular risk factors in young men: validation of some modifications of the hyperinsulinaemic, isoglycaemic glucose clamp technique.

Reduced peripheral sensitivity to insulin-stimulated glucose disposal, insulin resistance, is considered to be central in the metabolic cardiovascular syndrome. The hyperinsulinaemic euglycaemic glucose clamp technique was introduced by DeFronzo in 1979 and is regarded as the reference method for quantifying insulin resistance in skeletal muscle tissue. Recently, we used this technique in young men to relate insulin resistance (inverse of insulin sensitivity) to a number of established cardiovascular risk factors. The method has undergone numerous modifications since 1979 which have not been extensively validated. Therefore, we now describe the modified hyperinsulinaemic, isoglycaemic glucose clamp procedure performed in our laboratory and validate some of the modifications. Five young/middle-aged men were examined twice in three weeks and then re-examined after 4 years in the same way. The intrasubject day-to-day variability in insulin sensitivity was 5%. The average reduction in insulin sensitivity after 4 years was 21%. The last 60 min of the clamp offered a better basis for calculating glucose disposal rate (GDR) than the last 20 min. The variation in glucose measurements during clamp was 5%. We thus found that our modified isoglycaemic hyperinsulinaemic glucose clamp technique for assessing insulin sensitivity in skeletal muscle tissue is accurate and reproducible when performed in young/middle-aged men.

Adult↗

Estimates of insulin action in normal, obese and NIDDM man: comparison of insulin and glucose infusion test, CIGMA, minimal model and glucose clamp techniques.

Many methods of varying complexity are available for the measurement of insulin resistance (action) in man. No study has previously compared several of these in the same subjects to establish which is the most appropriate for routine use. We have, therefore, compared six methods: the hyperinsulinemic eu(iso)-glycaemic clamp (Eu), insulin glucose infusion test (IGI), hyperglycaemic clamp (Hy), continuous infusion of glucose with model assessment (CIGMA), minimal model (Min) and modified minimal model (Mod). Nineteen subjects with varying degrees of glucose tolerance were studied. Eight normal (BMI 22.5 +/- 1.5 kg/m2), six obese (BMI 38 +/- 5 kg/m2) and five NIDDM subjects (BMI 27 +/- 3 kg/m2) were investigated, in a randomized fashion, on separate days. The ratio of metabolic clearance rate of glucose (MCRG) and Insulin (I) was used as the measure of insulin action during Eu, Hy and IGI. Si was calculated as the index of insulin sensitivity from (Min) and (Mod) and CIGMA was obtained as previously described. MCRG was converted to Si to allow for direct comparison with (Min). Methods requiring incremental endogenous insulin secretion (which was highly variable) to calculate an index of insulin action (Si Min, Si Hy and CIGMA) failed to find an overall difference between groups. Only Si Eu (p = 0.007) and Si IGI (p = 0.001) demonstrated a significant overall group difference when Si was used. When MCRG/I was used, Eu, IGI and Hy were able to distinguish a significant overall group difference. With the exception of CIGMA and SiHy all other methods found a significant difference in insulin action between normals and NIDDM subjects. Only Eu and IGI could distinguish obese from normal, while only Si Min, could distinguish obese from NIDDM subjects. Eu and IGI were the only methods to be significantly correlated: normals Rs = 0.75, p < 0.05, obese Rs = 0.9, p < 0.05, and NIDDM Rs = 1.0, p < 0.05. In conclusion we have demonstrated that: 1) The insulin-glucose infusion test and the eu(iso)glycaemic clamp were significantly correlated in normals, obese and NIDDM subjects. 2) Only the eu(iso)glycaemic clamp and insulin glucose infusion test could significantly separate obese from normal subjects. 3) the IGI appears to be a practical, simple and precise method for measuring in vivo insulin action in man and gives results closely similar to those found with the hyperinsulinemic eu(iso)glycaemic clamp.

Adult↗

Comparison of the activity and pharmacokinetics of porcine insulin and human insulin (Novo) as assessed by the glucose clamp technique in normal and diabetic man.

Using the glucose clamp technique, human insulin (Novo) and natural porcine insulin were found to have identical potency in terms of glucose delivery in the second hour of i.v. infusion at low (0.02 U/kg/h; 265 +/- 25 versus 232 +/- 35 mg/min, respectively) and high (0.05 U/kg/h; 467 +/- 47 versus 452 +/- 41 mg/min, respectively) doses in normal man. Insulin metabolic clearance rates, serum in vivo half-life, and rate of onset of action were also similar. In insulin-dependent diabetic subjects, whose blood glucose levels were also held constant by feedback glucose infusion, the free insulin profiles after s.c. injection of neutral soluble human insulin and porcine insulin (0.2 U/kg) were identical, and similar to those after conventional and highly purified bovine insulin preparations. Glucose requirement to maintain normoglycemia for the first 5 h after injection was 49.6 +/- 8.2 g for conventional bovine insulin, 50.4 +/- 10.0 g for highly purified bovine, 40.5 +/- 6.9 g for human insulin, and 50.6 +/- 12.4 g for porcine insulin (NS by analysis of variance). No difference in insulin activity was detected when glucose requirement was expressed in terms of the prevailing free insulin concentration. Responses of blood intermediary metabolite levels were indistinguishable between all insulins in both studies.

Adult↗

Assessing effect of mixing insulins by glucose-clamp technique in subjects with diabetes mellitus.

The glucose-clamp technique was used to assess the effect on insulin activity of mixing clinically relevant doses of short- and longer-acting insulins in insulin-treated diabetic subjects. Mixtures of porcine regular and lente insulins resulted in a reduction in activity of the mixture compared with separate injection that was more apparent with premixing for 5 min before injecting than with premixing for 2 min. These findings were not explained by differences in volume of the injected insulin preparations. Mixing of porcine regular and bovine ultralente insulins for 2 min before injecting resulted in a reduced activity compared with separate injection. No difference in activity was obvious for porcine regular and NPH insulins given separately or premixed for 5 min. A reduction of activity during the 1st h after injection was observed when separate injection of one brand of these insulins (Velosulin or Insulatard) was compared with the manufactured mixture (Mixtard). These results indicate that premixing regular and NPH insulins in a 1-to-2 ratio does not alter the biological activity compared with separate administration of the insulins. However, the mixing of regular and insulin-zinc suspensions results in a loss of insulin activity, the magnitude of which depends on the time between mixing and injecting the insulin. The clinical significance of the effect of mixing on the efficacy of subcutaneous insulin therapy should be considered in the context that this is only one of many factors that may affect the activity of subcutaneously injected insulin.

Adult↗

Insulin sensitivity in patients with arterial insufficiency. Re-evaluation with the multilevel glucose clamp technique.

Previous studies have claimed that changes in insulin and glucose metabolism in patients with peripheral arterial insufficiency indicate an increased sensitivity to insulin for glucose uptake. We have re-evaluated this concept in 11 patients with intermittent claudication and 11 matched controls with a multilevel euglycaemic glucose clamp technique. The groups were matched for age, sex and body composition but not completely for smoking habits and physical fitness. Although the control group had a normal physical fitness the patients had 40% lower maximal exercising capacity. The patients' maximal walking capacity was 186 +/- 27 m evaluated on a treadmill. No patient with ischaemic ulcers or rest pain were included. The euglycaemic glucose clamp was performed at five insulin plateau levels (70, 110, 190, 590 and 1440 mU/l) of one h duration each and whole body glucose uptake during the last 20 min was calculated. No differences in maximal glucose uptake (Vmax) or insulin level for half maximal glucose uptake (Km) between the groups were observed. The concentration or the magnitude of the decrease in arterial FFA levels did not differ significantly between the groups at any physiological insulin level. This study can not confirm previously described changes in insulin sensitivity in patients with arterial insufficiency. Although the discrepancy between present and previous results remains unclear it may reflect the combined effects of different methods used, including the selection of reference patients, rather than an increased insulin sensitivity in patients with arterial insufficiency. This study suggests that previous conclusions based on glucose tolerance tests should be interpreted with caution.

Biological Transport, Active↗

Study of hypoglycemic patients by the glucose clamp technique using the artificial pancreas.

Using the artificial pancreas, blood glucose levels were maintained at 80 mg/dl in nine hypoglycemic patients (four with histologically proven insulinomas and five with nontumoral hypoglycemia) and in four normal subjects during a 24-h fast. The amount of glucose used, serum insulin levels, and glucose clearance were higher in patients with nontumoral hypoglycemia than in normal subjects and highest in the patients with an insulinoma. Surgical or pharmacological treatment resulted in normalization of all parameters. In contrast to the 72-h fast, the 24-h glucose clamp technique allowed the study of hypoglycemic patients without inducing hazardous hypoglycemia.

Adenoma, Islet Cell↗

Hormonal and metabolic responses to glucose infusion in sepsis studied by the hyperglycemic glucose clamp technique.

Although nutritional support is vital to treatment of severe sepsis, the septic patient does not respond normally to glucose infusion. We have used the hyperglycemic glucose clamp technique to investigate the initial hormonal and metabolic responses of the septic patient to glucose under controlled conditions. The plasma glucose concentration was raised to and maintained at 12 mmol/liter for 2 hr in 12 septic patients and 11 normal controls. Glucose utilization, assessed from the amount infused, was significantly depressed in the patients, despite similar plasma insulin concentrations in the two groups. Forearm glucose uptake was similarly impaired. Despite very similar plasma free fatty acid concentrations in the two groups, which were suppressed equally by the glucose infusion, whole-body fat oxidation was elevated in the patients compared with the controls, and suppressed to a lesser extent in response to glucose. Glycerol and ketone body concentrations were elevated in the patients in keeping with a picture of accelerated release, clearance, and oxidation of fatty acids. Plasma cortisol, epinephrine, and norepinephrine concentrations were elevated in the septic patients in a severity-related manner, but not to high levels compared with experimental work. Norepinephrine showed no response to the glucose infusion in either group. Plasma glucagon concentrations were not significantly elevated in the septic patients. We conclude that the hyperglycemic glucose clamp provides a useful model for studying glucose intolerance in sepsis. Impaired glucose utilization in septic patients is associated with increased fat oxidation, although the hormonal basis for these changes is still unclear.

Adult↗

A comparative study of the activity of biosynthetic human insulin and pork insulin using the glucose clamp technique in normal subjects.

The activity of biosynthetic human insulin (BHI) has been compared with that of pork insulin using the glucose clamp technique in normal subjects. After a baseline period, insulin was infused at 0.02 U/kg/h for 2 h, then 0.032 U/kg/h for 2 h, and finally 0.05 U/kg/h for 2 h. Glucose was clamped at baseline values using a glucose-controlled insulin infusion system (Biostator) and the amount of glucose infused to maintain normoglycemia calculated for each insulin dose for the two insulins. C-peptide levels decreased with both insulins, suggesting suppression of endogenous insulin secretion. Serum insulin levels attained were the same for both insulins. There were no significant differences in either total glucose infused or glucose infused during the last 30 or 60 min at each insulin dose for the two insulins. Intermediary metabolite responses to the infusion of the two insulins were similar. We conclude that in normal human beings, BHI shows identical metabolic activity with pork insulin.

Adult↗

Determination of reference range values indicative of glucose metabolism and insulin resistance by use of glucose clamp techniques in horses and ponies.

OBJECTIVES: To acquire reference range values indicative of glucose metabolism by use of the hyperglycemic clamp technique in healthy horses and evaluate the usefulness of the euglycemic hyperinsulinemic clamp technique in healthy horses and ponies. ANIMALS: Dutch Warmblood horses and 4 Shetland ponies. PROCEDURE: The hyperglycemic clamp technique was used for quantification of the sensitivity of beta cells to exogenous glucose infusion in horses. The euglycemic hyperinsulinemic clamp technique was used to determine the sensitivity and responsiveness of tissues to exogenous insulin in horses and ponies. RESULTS: During the hyperglycemic clamp technique, the mean amount of glucose metabolized (M) in horses was 0.011 +/- 0.0045 mmol/kg x min(-1) (95% confidence interval [CI], 0.0018 to 0.020 mmol/kg x min(-1); range, 0.000035 to 0.021 mmol/kg x min(-1)) and the mean M value-to-plasma insulin concentration (I) ratio (ie, mmol of glucose/kg x min(-1) per pmol of insulin/L x 100) was 0.017 +/- 0.016 (95% CI, -0.014 to 0.049; range, 0.000025 to 0.055). During the euglycemic hyperinsulinemic clamp technique, the mean M value was 0.014 +/- 0.0055 mmol/kg x min(-1) (95% CI, 0.0026 to 0.025 mmol/kg x min(-1); range, 0.0042 to 0.023 mmol/kg x min(-1)) in horses and 0.0073 +/- 0.0020 mmol/kg x min(-1) (95% CI, 0.0034 to 0.011 mmol/kg x min(-1); range, 0.0049 to 0.011 mmol/kg x min(-1)) in ponies. The M value was significantly lower in ponies than in horses, whereas the M:I ratios were not significantly different between horses and ponies. CONCLUSION AND CLINICAL RELEVANCE: Glucose clamp techniques offer good methods to investigate glucose metabolism in horses and ponies. A higher degree of insulin resistance was found in ponies, compared with Dutch Warmblood horses.

Animals↗

Glucose clamp technique: a method for quantifying insulin secretion and resistance.

Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.

Glucose↗

Insulin sensitivity and exogenous insulin clearance in Graves' disease. Measurement by the glucose clamp technique and continuous indirect calorimetry.

Insulin sensitivity was measured in a group of seven thyrotoxic patients and in a group of seven normal subjects by means of the glucose clamp technique. Infusion of insulin at a rate of 0.80 +/- 0.05 mU/kg X min in the hyperthyroid patients and of 0.55 +/- 0.04 mU/kg X min in the control group was performed to obtain a steady-state plasma insulin concentration of approximately 50 microU/ml. Substrate oxidation rates were measured in the postabsorptive state and during the 2 h of the clamp by means of continuous indirect calorimetry. In the postabsorptive state, hyperthyroid patients presented a preferential oxidation of lipids. During the period 60-120 min of the clamp, mean plasma glucose (92 +/- 2 versus 93 +/- 2 mg/dl), insulin (50 +/- 5 versus 58 +/- 3 microU/ml), and total glucose metabolism (5.8 +/- 0.7 versus 6.1 +/- 0.3 mg/kg X min) were similar in the hyperthyroid patients and the control subjects. The rate of glucose oxidation was higher in hyperthyroid patients than in control subjects (4.3 +/- 0.5 versus 2.2 +/- 0.2 mg/kg X min, P less than 0.001), while that of lipid oxidation was similar in both groups (0.6 +/- 0.2 versus control 0.7 +/- 0.1 mg/kg X min). The calculated metabolic clearance rate of insulin was markedly higher in the hyperthyroid patients (1144 +/- 132 ml/min) than in the normal subjects (812 +/- 56 ml/min, P less than 0.025). It is concluded that insulin sensitivity is not altered in the thyrotoxic state. The major route of insulin-stimulated glucose disposal in the hyperthyroid patients appears to be glucose oxidation.

Adult↗

In vivo hepatic and peripheral insulin sensitivity in rats with non-insulin-dependent diabetes induced by streptozocin. Assessment with the insulin-glucose clamp technique.

Non-insulin-dependent diabetes mellitus (NIDDM) was obtained in adult female rats by neonatal administration of streptozocin (STZ). At 2 mo of age, the basal plasma glucose values in the postabsorptive state were elevated, the glucose disappearance rate measured after intravenous (i.v.) glucose load was significantly lower in the diabetic than in control rats, and in vivo glucose-induced insulin release was drastically reduced. To quantify and characterize the in vivo insulin sensitivity in rats with NIDDM, we have used the insulin-glucose clamp technique. The effects of different concentrations of insulin on glucose production, glucose utilization, and glucose clearance (measured by using 3-3H-glucose) were studied in anesthetized diabetic or control rats while in the postabsorptive state. An inherent condition to set up a valid experimental design was to take into consideration, in the diabetics, the influence of the high blood glucose concentration on glucose uptake and glucose production, since the blood glucose concentration by itself affects these two parameters by a mass action effect independent of insulin. The issue was addressed by evaluating glucose production and utilization in three experimental groups: diabetics clamped at their basal blood glucose level (170 mg/dl), controls clamped at their basal blood glucose level (110 mg/dl), and controls clamped at high blood glucose level (170 mg/dl). In the basal state, glucose production was significantly higher in the diabetics than in controls. When plasma insulin was clamped at submaximal levels (300 microU/ml), the suppression of glucose production was significantly more important in the diabetics than in the two control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Decreased fetal movements with sustained maternal hyperglycemia using the glucose clamp technique.

The purpose of this study was to evaluate the effect of sustained maternal hyperglycemia (120 mg/dl) on fetal activity. The glucose infusion study group was comprised of nine healthy gravidas between 36 and 40 weeks' gestation, and six patients served as controls. The protocol design included an overnight fast for all patients. Fetal movements were evaluated by external fetal monitoring. A 2-hour preinfusion evaluation of fetal activity served as the baseline control for each patient studied. Study patients then received a glucose infusion by a glucose clamp technique to maintain a sustained hyperglycemia of 120 mg/dl for 3 hours. After the glucose infusion, fetal movements were observed for 1 hour. Control patients received a saline infusion for 2 hours after a 2-hour baseline evaluation. Maternal hyperglycemia was associated with a significant decrease of fetal movements greater than 1 second duration during the first hour of glucose infusion. Fetal movements returned to baseline during the second and third hours of glucose infusion. Saline infusion was not associated with a decrease in fetal activity. We conclude that sustained maternal hyperglycemia is associated with a transient decrease in fetal movement during the first hour of glucose infusion followed by a return to the control (preinfusion) level of fetal activity. These data may have implications in the study of fetal behavior in diabetes mellitus.

Blood Glucose↗

Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity.

OBJECTIVE: To evaluate whether the homeostasis model assessment (HOMA) is a reliable surrogate measure of in vivo insulin sensitivity in humans. RESEARCH DESIGN AND METHODS: In the present study, we compared insulin sensitivity as assessed by a 4-h euglycemic (approximately 5 mmol/l) hyperinsulinemic (approximately 300 pmol/l) clamp with HOMA in 115 subjects with various degrees of glucose tolerance and insulin sensitivity. RESULTS: We found a strong correlation between clamp-measured total glucose disposal and HOMA-estimated insulin sensitivity (r = -0.820, P<0.0001), with no substantial differences between men (r = -0.800) and women (r = -0.796), younger (aged <50 years, r = -0.832) and older (r = -0.800) subjects, nonobese (BMI <27 kg/m2, r = -0.800) and obese (r = -0.765) subjects, nondiabetic (r = -0.754) and diabetic (r = -0.695) subjects, and normotensive ( r = -0.786) and hypertensive (r = -0.762) subjects. Also, we found good agreement between the two methods in the categorization of subjects according to insulin sensitivity (weighted k = 0.63). CONCLUSIONS: We conclude that the HOMA can be reliably used in large-scale or epidemiological studies in which only a fasting blood sample is available to assess insulin sensitivity

Adult↗

The pharmacokinetics of subcutaneous regular insulin in type I diabetic patients: assessment using a glucose clamp technique.

We recently reported that the peak effect and duration of action of regular insulin injected sc were prolonged in diabetic patients and were not related to the presence of insulin antibodies. The results suggested that the ambient level of plasma glucose might be an important factor in determining the pharmacokinetics of regular insulin. In the present study we used a glucose clamp technique, which minimizes interference by counterregulatory phenomena, to study the pharmacokinetics of regular insulin injected sc at 2 different blood glucose concentrations [276 +/- 7 (+/- SEM) and 130 +/- 5 mg/dl] in 10 insulin-dependent diabetic patients. The patient's blood glucose concentration was maintained constant by means of a variable rate iv infusion of 20% dextrose in water after sc injection of regular insulin (0.2 U/kg) in the deltoid region of the arm. The onset of insulin action occurred at similar times at both glucose concentrations (0.6 +/- 0.1 h at 276 mg/dl vs. 0.5 +/- 0.1 h at 130 mg/dl; P greater than 0.05). Peak insulin action (determined from the time of the maximal glucose infusion rate) was delayed in the studies done at 276 mg/dl (4.7 +/- 0.2 h) compared to that in studies done at mean glucose concentrations of 130 mg/dl (4.3 +/- 0.2 h; P less than 0.05). The duration of insulin action was also significantly prolonged in the studies done at the higher glucose concentrations (9.1 +/- 0.3 h at 276 mg/dl vs. 7.7 +/- 0.2 h at 130 mg/dl; P less than 0.01). These results confirm previous reports of prolonged insulin action in diabetic patients, especially in the presence of hyperglycemia.

Adult↗

Insulin resistance and changes in the blood coagulation-fibrinolysis system after a glucose clamp technique in patients with type 2 diabetes mellitus.

We investigated the relationship between changes in insulin resistance and blood coagulation-fibrinolysis following institution of a glucose clamp (GC) in patients with type 2 diabetes mellitus. We studied 35 type 2 diabetic patients (19 males and 16 females, mean age at 58.3 +/- 11.9 years) and 10 healthy subjects. The hyperinsulinemic euglycemic GC technique was performed using on artificial pancreas. The degree of insulin resistance was determined from the glucose infusion rate (GIR) calculated from the GC technique. The GIR in type 2 diabetic patients was markedly reduced compared to that in healthy subjects. The GIR was significantly and negatively correlated with the body mass index and the serum concentrations of the fasting immunoreactive insulin (FIRI). The plasma concentrations of thrombomodulin (TM) and tissue plasminogen activator (tPA) in the diabetic patients were significantly higher than those in the healthy subjects. The plasma concentrations of plasminogen activator inhibitor 1 in the diabetic patients tended toward higher than those in the healthy subjects. The elevated plasma concentrations of TM and tPA in diabetes were significantly lowered following a GC technique. Patients with advanced nephropathy had significant higher concentrations of TM and tPA compared to healthy subjects. We concluded that diabetic patients have abnormalities in the blood coagulation-fibrinolytic system that can be improved by the GC technique.

Albuminuria↗