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Biomedical subjects

C K Lardinois

Publications and source records attributed to C K Lardinois.

29 records · Page 2Linked to original sources

Polyunsaturated fatty acids augment insulin secretion.

Carbohydrate intolerance is positively correlated with animal fat consumption and is more common in beef eating populations. In contrast, individuals consuming diets comprised of polyunsaturated fats have a lower incidence of diabetes mellitus. To test the hypothesis that dietary fats may influence carbohydrate metabolism, serum glucose, insulin, and gastric inhibitory polypeptide (GIP) responses to three mixed test meals of varying fatty acid composition were assessed in 12 normal subjects. Fatty acids in the meals were either saturated fats or polyunsaturated fats derived from vegetables or fish. Each test meal provided 40% of a subject's calculated daily caloric requirement and contained approximately 45% carbohydrate, 40% fat, and 15% protein. Serum insulin responses were 62% higher (p less than 0.01) after the fish and 39% higher (p less than 0.01) after the vegetable meals compared to the saturated fat meal. No significant differences in insulin responses were observed between the vegetable and fish meals. Serum glucose concentration was slightly higher (p less than 0.02) during the fish meal than with the vegetable or saturated fat meals. The GIP levels were comparable following the fish and vegetable meals and were 25% lower than those observed with the saturated fat meal. These findings suggest that diets enriched with polyunsaturated fatty acids augment insulin secretion significantly more than a diet comprised primarily of saturated fatty acids. The mechanism for this increased insulin secretion is unknown but did not appear to be mediated through differences in serum glucose values or through the insulin-otrophic effects of GIP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Reduced plasma high density lipoprotein-cholesterol concentrations need not increase when hyperglycemia is controlled with insulin in noninsulin-dependent diabetes mellitus.

The ability of intensive insulin treatment to increase plasma high density lipoprotein (HDL)-cholesterol levels was evaluated in 12 patients with noninsulin-dependent diabetes mellitus. Patients were treated for 6 weeks with one daily morning injection of ultralente insulin, in combination with administration of regular insulin before breakfast, lunch, and dinner. The mean (+/- SEM) fasting plasma glucose concentration fell from 289 +/- 21 to 122 +/- 9 mg/dl (P less than 0.001), and the mean hourly postprandial glucose concentration fell from 313 +/- 24 to 102 +/- 7 mg/dl (P less than 0.001). In addition, insulin treatment was associated with a reduction in both fasting plasma triglyceride (256 +/- 45 to 137 +/- 18 mg/dl; P less than 0.001) and cholesterol (224 +/- 25 to 199 +/- 19 mg/dl; P less than 0.05) concentrations. However, plasma HDL-cholesterol concentrations, which were low to begin with, did not rise in association with excellent glycemic control. These results demonstrate that hyperglycemia and hypertriglyceridemia can be effectively reduced by an aggressive program of insulin treatment in patients with noninsulin-dependent diabetes mellitus, but this intervention need not lead to an improvement in the abnormal HDL-cholesterol metabolism in these patients.

Adult↗

Glyburide in non-insulin-dependent diabetes. Its therapeutic effect in patients with disease poorly controlled by insulin alone.

Glyburide, a second-generation sulfonylurea compound, was combined with insulin to evaluate its therapeutic effectiveness in 14 patients with non-insulin-dependent diabetes mellitus (NIDDM), poorly controlled by insulin alone. Patients were studied before and three months after the addition of glyburide to their insulin program. Fasting plasma glucose concentration fell an average of 57 mg/dL, associated with an approximately 25% reduction in postprandial glucose response. Therapeutic responses varied widely from patient to patient; the greatest improvement in diabetic control was seen in heavier patients, who had retained the ability to secrete insulin in response to meals and who were not excessively insulin resistant. The glyburide-induced fall in plasma glucose concentration was associated with improvements in both insulin secretion and insulin action, but only the enhanced insulin action correlated with the reduction in fasting and postprandial glucose levels. Thus, diabetic control was significantly improved by glyburide. Combined insulin-sulfonylurea therapy may be useful in the treatment of NIDDM that cannot be easily controlled with either agent alone.

Adult↗

Estimates of in vivo insulin action in humans: comparison of the insulin clamp and the minimal model techniques.

The insulin clamp technique, which is often assumed to measure the ability of insulin to stimulate glucose uptake, actually measures both insulin-independent and insulin-dependent glucose uptake. In contrast, the minimal model technique, recently introduced by Bergman, Philips and Cobelli (1981), attempts to directly estimate insulin sensitivity (insulin-dependent glucose uptake = S1) by measurement of plasma glucose and insulin values during a 3 hour intravenous glucose tolerance test (IVGTT). In the present study estimates of insulin action derived from the insulin clamp and the minimal model technique were compared in 20 humans with varying degrees of glucose tolerance. The insulin response during the IVGTT was too low to permit calculation of S1 in 5 subjects - 4 with Type II diabetes and 1 with normal glucose tolerance. Although the correlation coefficient between the two tests in the other 15 patients was statistically significant (r = 0.53, P less than 0.05), this statement is somewhat misleading. Thus, S1 in the 4/7 patients with Type II diabetes in whom it could be measured was zero, and the correlation between estimates of insulin action with the two techniques in the 11 non-diabetic patients was not statistically significant (r = 0.41, P = NS) when these 4 patients were removed from the analysis. In conclusion, these data indicate that there was only a weak correlation between estimates of insulin action assessed with the insulin clamp and the minimal model techniques. One explanation for this observation is that the insulin-independent component of total glucose disposal both varies widely among patients and contributes significantly to glucose uptake as assessed by the insulin clamp technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Gastric inhibitory polypeptide responses to nutrients in Caucasians and American Indians with obesity and noninsulin-dependent diabetes mellitus.

Serum gastric inhibitory polypeptide (GIP), insulin, and glucose responses to either a 75-g oral glucose challenge or a 500-cal liquid test meal were determined in 141 Caucasians and American Indians. The Caucasians were normal weight, averaging 101 +/- 3% (+/-SEM) ideal BW (IBW), or were obese (168 +/- 21% IBW) and had normal glucose tolerance (n = 77), impaired glucose tolerance (IGT; n = 12), or noninsulin-dependent diabetes mellitus (NIDDM; n = 19). The American Indians were all obese (144 +/- 6% IBW) and had either normal glucose tolerance (n = 22) or NIDDM (n = 11). In all study subjects, including obese individuals with and without glucose intolerance, diabetic patients both thin and obese, and lean subjects with impaired glucose tolerance, fasting serum insulin and GIP, and incremental glucose, insulin, and GIP were greater than they were in normal lean subjects, especially during the first hour of the tests. Obese subjects and diabetic patients exceeded lean normal subjects by up to 620% for glucose, up to 640% for insulin, and up to 360% for GIP during the first hour after glucose ingestion or the test meal. Exceptions were two groups with the most severe diabetes in whom incremental insulin values after oral glucose were only 70% (thin Caucasians) and 110% (obese Indians) that of lean normal subjects. The smallest differences in GIP responses occurred between lean normal subjects and obese nondiabetic Caucasians tested with either a meal or oral glucose, whereas American Indians consistently had the greatest insulin and GIP responses to the tests. High fasting GIP and exaggerated GIP increments in response to nutrients could be attributed to neither obesity nor diabetes alone nor to the type of nutrient used to stimulate its release, but, instead, may be genetic or dietary in origin or may be due to other as yet unidentified factors. High basal GIP and exaggerated nutrient-stimulated GIP release were associated with hyperinsulinemia, except in the most severe diabetic patients. These observations suggest that exaggerated GIP release, along with a greater rise in serum glucose in response to nutrients, may play a role in the pathogenesis of the hyperinsulinemia of obesity and early NIDDM.

Adult↗

Increased gastric inhibitory polypeptide is not reduced in patients with noninsulin-dependent diabetes mellitus treated with intense insulin therapy.

Serum glucose and gastric inhibitory polypeptide (GIP) responses during mixed test meals and primed continuous infusion of insulin using the insulin clamp technique were studied in nine patients with noninsulin-dependent diabetes mellitus (NIDDM) before and after vigorous insulin treatment. Fasting serum glucose concentrations fell an average of 167 mg/dl (P less than 0.001), and there was a 67% reduction (P less than 0.001) in the postprandial glucose response. Mean hemoglobin A1c declined and paralleled the fall in serum glucose concentrations (9.2 +/- 0.5% to 5.9% +/- 0.3%; P less than 0.01). This improvement in glycemic control, however, was not associated with any appreciable change in GIP secretion. Basal and meal-stimulated serum GIP levels were not reduced after intense insulin therapy. Furthermore, hyperinsulinemia at physiological (100 microU/ml) and superphysiological (1000 microU/ml) levels failed to reduce GIP secretion before and after insulin therapy. Before insulin therapy, seven patients had elevated basal GIP levels and five had increased GIP levels after meals compared to values in nondiabetic subjects. Insulin administration did not alter these elevated GIP levels. These findings suggest that the increased meal-stimulated GIP secretion in some patients with NIDDM is not due to a failure of insulin feedback on GIP secretion.

Adult↗

Moderate weight loss and sulfonylurea treatment of non-insulin-dependent diabetes mellitus. Combined effects.

Hypocaloric liquid formula diets were given for one month to 20 moderately obese patients with non-insulin-dependent diabetes mellitus divided into two equal groups; group 1 was treated with weight loss alone; group 2 received glipizide in addition to the hypocaloric diet. Mean weight loss was similar in the two groups (6.5 +/- 0.6 v 6.4 +/- 0.5 kg) and was associated with a statistically significant fall in mean fasting plasma glucose values from 293 +/- 15 to 232 +/- 24 mg/dL (group 1) and from 281 +/- 15 to 152 +/- 7 mg/dL (group 2). This was associated with 13% (group 1) and 36% (group 2) decrements in total postprandial glucose response. Neither fasting nor postprandial insulin levels changed significantly with weight loss, but estimates of insulin-stimulated glucose disposal demonstrated a 15% (group 1) and 42% (group 2) improvement. Finally, fasting plasma cholesterol and triglyceride concentrations fell significantly in both groups.

Blood Glucose↗

Cimetidine blocks testosterone synthesis.

Although an assortment of endocrine dysfunctions are reported in men treated with cimetidine hydrochloride, gonadotropin and sex steroid levels are usually normal. A 66-year-old man with previously normal sexual function presented with breast tenderness and sexual dysfunction after receiving cimetidine. His plasma testosterone level was low, and elevated gonadotropin levels suggested a primary testicular disorder. His sexual dysfunction improved and his plasma testosterone level rose to normal after cimetidine therapy was discontinued. Readministration of cimetidine therapy resulted in the prompt recurrence of his sexual problems and low testosterone level. A reversible defect in 17-beta-hydroxysteroid dehydrogenase is the mechanism postulated to have caused his low testosterone level. While the frequency of this abnormality is uncertain, its reversible nature and the wide use of cimetidine make it an important cause of sexual dysfunction in men.

Aged↗

Insulin-stimulated glucose disposal increases with time in patients with non-insulin-dependent diabetes mellitus.

The relative effects of time versus ambient glucose concentration on insulin-stimulated glucose uptake was estimated by performing 5-h insulin clamp studies in patients with NIDDM. Each experimental subject was studied three times, at steady-state plasma insulin levels approximately 2000 microU/ml, but at different steady-state plasma glucose concentrations (studies A, B, and C). Study A consisted of a 5-h clamp, with plasma glucose level maintained at the basal level of fasting hyperglycemia; study B differed in that the basal level of fasting hyperglycemia was reduced during the first hour to approximately 80 mg/dl, and maintained there for the next 4 h; and study C was carried out by clamping the patient at the basal glucose level for 2 h, lowering the glucose concentration to approximately 80 mg/dl during the third hour, and then clamping at this level for the last 2 h. The glucose metabolic clearance rate (MCR) was calculated from 60 to 120 min and from 240 to 300 min during each study, and the results indicated that values for glucose MCR were time dependent, being significantly greater (20-60%) in the fifth than in the second hour in two (studies A and B) of the three studies. In contrast, glucose MCR was independent of plasma glucose concentration, and relatively constant in each subject, as long as it was measured during the same time period. The time-dependent increase in glucose MCR was associated with an approximate 30% increase in steady-state plasma insulin concentrations when comparing the second and fifth hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Acarbose treatment of non-insulin-dependent diabetes mellitus.

Acarbose is a newly developed inhibitor of intestinal alpha-glucosidase, and in the current study its ability to lower plasma glucose levels was studied in 12 patients with non-insulin-dependent diabetes mellitus, poorly controlled on diet plus sulfonylurea drugs. Patients were studied before and three months after the addition of acarbose to their treatment program, and there was a notable fall in postprandial plasma glucose concentrations that approximated 60 mg/dL. When acarbose therapy was discontinued in five patients, plasma glucose levels rapidly returned toward pretreatment levels. In addition to the improvement in glycemia, acarbose treatment also led to a notable reduction in Hb A1c and triglyceride concentrations. Finally, considerable individual variation was noted in the response to acarbose, and the results in four patients were quite dramatic, with striking reductions in both fasting and postprandial glucose concentrations. These data suggest that acarbose may be a useful addition in the treatment of patients with non-insulin-dependent diabetes mellitus.

Acarbose↗