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Biomedical subjects

M C Riddle

Publications and source records attributed to M C Riddle.

At least 37 records · Page 2Linked to original sources

The mental efficiency of the elderly person with type II diabetes mellitus.

Cognitive function is often impaired in type I diabetes mellitus, especially when onset is in early childhood. Limited evidence suggests similar impairment in the much larger population of older persons with type II diabetes. We report here the results of 13 measures of mental efficiency in persons between 65 and 77 years of age without gross mental impairment. Nineteen persons with type II diabetes were compared with 19 controls with normal glycosylated hemoglobin values and to seven persons not previously known to have diabetes but who had elevated glycosylated hemoglobin. Significant differences (P less than .05) between the nondiabetic control and diabetic groups were noted on eight of the 13 tests. The group of subjects with elevated glycosylated hemoglobins showed levels of cognitive performance intermediate between the normal and known diabetic groups on the majority of tests. These findings confirm that mental efficiency is frequently impaired in older persons with diabetes. Given the high prevalence of diabetes in the aging population we suggest that diabetes may be another important factor contributing to premature loss of cognitive abilities in older people.

Aged↗

Evening insulin strategy.

A series of regimens based on intermediate-acting insulin given in the evening have been proposed as an alternative to conventional insulin therapy for non-insulin-dependent diabetes mellitus (NIDDM). This concept dates back to the earliest use of sustained-action insulin and has a rationale strengthened by recent physiological insights. Specifically, the predominance of fasting over postprandial hypoglycemia and occurrence of the dawn phenomenon in NIDDM argue for carefully timed overnight delivery of insulin. High nocturnal concentrations of free fatty acids in NIDDM may contribute to hepatic insensitivity to insulin and fasting hyperglycemia and can be suppressed by evening insulin. Although several clinical studies suggest that evening insulin regimens are safe and effective, their role in clinical practice is not yet established. Further study of this approach may clarify not only its proper use but also the best use of conventional strategies.

Blood Glucose↗

Diabetic neuropathies in the elderly: management update.

Diabetic neuropathy is a common, varied, and disabling disease that is potentially responsive to therapy. While its pathogenesis is as yet unclear, its clinical presentations and natural history are well known. Present information suggests glycemic control can prevent neuropathy and in some cases cause established neuropathy to regress. Drug therapy is useful only for painful neuropathy. Avoidance of alcohol and behavioral and surgical relief of nerve entrapment are helpful in certain cases.

Aged↗

Efficacy of bedtime NPH insulin with daytime sulfonylurea for subpopulation of type II diabetic subjects.

Although insulin and sulfonylureas often have additive clinical effects when used in combination for type II (non-insulin-dependent) diabetes, these results are variable and a clinical role for this approach is not yet established. This study tests the efficacy of a specific combined regimen for a subpopulation of patients with a randomized double-masked placebo-controlled crossover design and under conditions similar to those of clinical practice. Twenty subjects with limited duration (less than 15 yr) type II diabetes who were moderately obese (less than 160% ideal wt) and proved imperfectly controlled on 10 mg glyburide twice daily completed two 4-mo crossover protocols, comparing a single injection of NPH insulin in the evening plus 10 mg glyburide in the morning with insulin plus placebo. Insulin dose was adjusted by experienced endocrinologists seeking the best glycemic control consistent with safety. All subjects had glycosylated hemoglobin values less than or equal to 150% of the control mean on combined therapy, and combined therapy was superior to insulin alone (fasting plasma glucose 8.0 +/- 0.3 vs. 11.1 +/- 0.6 mM, P less than .01; glycosylated hemoglobin 9.8 +/- 0.1 vs. 10.6 +/- 0.2%, P less than .01). Despite greater weight gain on combined therapy, blood pressure and plasma lipid concentrations were the same on the two regimens. These results suggest this simple regimen offers another option, besides multiple injections of insulin, for patients of this kind who are unsuccessful with a sulfonylurea or a single injection of insulin alone.

Adult↗

New tactics for type 2 diabetes: regimens based on intermediate-acting insulin taken at bedtime.

In type 2 diabetes mellitus, achieving normal fasting plasma glucose concentrations is probably more important than control of postprandial concentrations. It is suggested that, for some patients, treatment based on intermediate-acting insulin taken at bedtime will have more success than conventional regimens in lowering fasting, and thereby mean, plasma glucose concentrations, without causing hypoglycaemia.

Blood Glucose↗

The effects of a high-carbohydrate low-fat cholesterol-restricted diet on plasma lipid, lipoprotein, and apoprotein concentrations in insulin-dependent (type I) diabetes mellitus.

Six women with well-defined insulin-dependent diabetes mellitus (IDDM) were studied for 4 weeks during a control diet containing 45% of the calories as carbohydrate, 40% fat (P/S ratio 0.14), 15% protein, and 580 mg of cholesterol, and for 6 weeks during a high-carbohydrate low-fat cholesterol-restricted diet with 65% carbohydrate, 20% fat (P/S ratio 1.40), 15% protein, and 62 mg cholesterol. All subjects completed both dietary periods in a crossover experimental design. Individual menus were subject-selected from a calculated exchange list containing conventional food items consistent with current American dietary patterns. The diets were well-tolerated by all subjects. Total plasma cholesterol decreased from 201 to 156 mg/100 mL (P less than 0.05) during the cholesterol-restricted diet, while total plasma triglyceride (TG) increased from 96 to 115 mg/100 mL (P less than 0.01). During this same period, very low-density lipoprotein cholesterol (VLDL-C) and VLDL-TG increased from 17 to 21 mg/100 mL (P less than 0.05) and from 59 to 76 mg/100 mL (P less than 0.001), respectively, while low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) decreased from 126 to 90 mg/100 mL (P less than 0.05) and from 50 to 39 mg/100 mL (P less than 0.05), respectively. LDL-C/HDL-C and total-C/HDL-C ratios were lower but not significantly different, and LDL-TG and HDL-TG were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effects of subject-selected high carbohydrate, low fat diets on glycemic control in insulin dependent diabetes mellitus.

In the present study, six women with insulin dependent diabetes mellitus (IDDM) were assigned to begin either a control diet containing 45% of the calories as carbohydrate, 40% fat, and 15% protein for four weeks, or a high carbohydrate, low fat diet with 65% carbohydrate, 20% fat, and 15% protein for six weeks. All subjects completed both periods in a cross-over experimental design. Individual menus varied, and were subject-selected from a calculated exchange list consisting of conventional food items. Subjects selected an equal distribution of carbohydrate from simple and complex sources during both dietary periods, and dietary fiber intake was only modestly greater during the high carbohydrate diet (50 g) than in the control diet period (28 g). No significant changes occurred in any measures of glycemic control between the control and high carbohydrates diets; fasting serum glucose 215 vs 213 mg/100 ml; preprandial serum glucose 214 vs 200 mg/100 ml; 24 hour urine glucose 36 vs 31 g/day; and glycosylated hemoglobin 10.3 vs 10.5% Hb A1, respectively. Similarly, insulin dose was unchanged during the control (38 IU/day) and experimental (38 IU/day) periods. These findings indicate that the application of present dietary recommendations to persons with IDDM in a realistic clinical setting led to neither an improvement nor a deterioration of glycemic control.

Adult↗

The composition and nutritional adequacy of subject-selected high carbohydrate, low fat diets in insulin-dependent diabetes mellitus.

The composition and nutritional adequacy of subject-selected high carbohydrate, low fat diets were investigated in six women with insulin-dependent diabetes mellitus. Subjects were randomly assigned to begin either the experimental diet with 65% carbohydrate, 20% fat, and 15% protein for 6 wk, or a control diet with 45% carbohydrate, 40% fat, and 15% protein for 4 wk. All subjects completed both dietary periods in a cross-over experimental design. Subjects were allowed free selection in their choice of carbohydrate-rich foods. The resulting selections produced diets with 51% simple and 49% complex carbohydrates and 50 g of dietary fiber during the experimental diet. Similar proportions were also selected during the control diet. Blood chemistries revealed no significant changes in thiamin, riboflavin, vitamin B6, pyridoxal 5'-phosphate, ascorbate, vitamin E, calcium, selenium, or zinc concentrations between the two dietary periods. With the exception of vitamin B6, all vitamin and mineral values were within normal respective ranges. Vitamin B6 status, as assessed by pyridoxal 5'-phosphate, were below or just above the levels of marginal deficiency (2.2 nmol/100 ml) in four of the six individuals, but the lower level observed occurred independent of the dietary treatments. The present study demonstrates that subject-selected high carbohydrate, low fat diets were much lower in complex carbohydrates and fiber than diets previously tested. In addition, the concentration of several nutrients did not appear to be adversely affected by these diets.

Adult↗

Treatment of diabetes with insulin. From art to science.

Improved understanding of the physiology and pharmacokinetics of insulin and new therapeutic devices allow an increasingly rational approach to the treatment of diabetes with insulin. The complexity of the regimen necessary for successful control of blood glucose levels depends largely on a patient's relative deficiency of endogenous insulin. Patients initially treated successfully with single or twice-a-day injections often, as the amount of endogenous insulin dwindles, progress to a complex regimen more closely mimicking normal patterns of secretion. Self-monitoring of blood glucose values and attention to many simple factors affecting absorption of insulin and glycemic behavior strongly enhance the success of all regimens. Patients and physicians must collaborate to plan and execute individualized therapeutic regimens using available tools to the best advantage.

Adult↗

The mass uptake of cholesterol ester from low density lipoproteins by cultured smooth muscle and adventitial cells of human aortas.

Cultured human smooth muscle and adventitial cells were incubated with human serum and low density lipoprotein (LDL) to study the uptake and accumulation of cholesterol ester from exogenous LDL. The cellular total cholesterol varied with the amount of LDL cholesterol in the medium. The cholesterol ester content increased 4-fold after 2 hours of incubation. A 6-fold rise occurred by 24 hours and continued to 72 hours. The cholesterol ester of the adventitial cells was markedly depleted by incubation with abetalipoproteinemic serum or with a lipid-depleted plasma fraction. By the use of 14C-labeled LDL free cholesterol in the incubation medium, we calculated that some 70-80% of the total accumulated cholesterol ester after 24 hours of incubation was derived from LDL cholesterol ester, and only 20-30% was synthesized by the cells. These studies demonstrated conclusively that human cells greatly increase their cholesterol ester mass after incubation with LDL.

Aorta↗

Two cholesterol ester hydrolases. Distribution in rat tissues and in cultured human fibroblasts and monkey arterial smooth muscle cells.

Hydrolytic activity against acetone-dispersed [4-14C]cholesterol oleate has been assayed as a function of pH in seven parenchymal tissues, blood cells, and plasma of the rat, as well as in cultured human fibroblasts and monkey (Macaca nemestrina) arterial smooth muscle cells. Both acid and neutral hydrolytic activities were present in all of these except rat plasma. The pH optima were in all cases close to pH 4.5 and pH 6.8. Acid activity was quite constant from tissue to tissue, while neutral activity varied greatly, being greatest in adrenal, testis, and adipose tissue. Subcellular fractionation of human fibroblasts allowed demonstration that activities at pH 4.5 and pH 6.8 were concentrated in different fractions, apparently lysosomal and polysomal, respectively. It appears most cell types, including fibroblasts and smooth muscle cells, contain two separate enzymes capable of hydrolyzing cholesterol esters. The neutral pH polysomal enzyme, which is especially prominent in certain tissues, may have a function related to the specialized roles of these tissues.

Animals↗

Cholesteryl ester hydrolytic acitivity of rat liver plasma membrane.

Cholesteryl ester hydrolyzing activity of rat liver plasma membranes was studied using acetone-dispersed [4-14-C] cholesteryl oleate as substrate. In contrast to whole liver homogenates which displayed ample activity at both acid (4.5) and neutral (6.2-7.4) pH, purified plasma membrane fractions contained little activity at neutral pH as compared to acid pH. Moreover, rate-zonal sucrose density-gradient centrifugation patterns of plasma membrane rich fractions suggested a specific association with plasma membrane only in the case of the acid activity. These findings suggest that in vivo hepatic cell surface membranes contain little or no cholesteryl ester hydrolytic activity at extracellular pH. They support the possibility that plasma lipoprotein cholesteryl esters enter hepatic parenchymal cells prior to hydrolysis.

Animals↗