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Biomedical subjects

P Raskin

Publications and source records attributed to P Raskin.

At least 73 records · Page 4Linked to original sources

Blurred vision: an overlooked initial presenting symptom of insulin-dependent diabetes mellitus.

Blurred vision, a well-known complication of uncontrolled diabetes mellitus, is occasionally overlooked as the first and only presenting symptom of type I diabetes mellitus. In this report we describe six type I diabetic patients whose first and only symptom of the disease was blurred vision, as documented by increased glycosylated hemoglobin. Institution of therapy was delayed until the classical symptoms of diabetes mellitus appeared.

Adult↗

Isolated symptomatic peripheral neuropathy in type 1 insulin-dependent diabetes mellitus.

Diabetic neuropathy is probably the most frequent of the chronic complications of diabetes, and is usually found in association with diabetic retinopathy and/or nephropathy. We report seven patients with long-standing insulin-dependent diabetes mellitus in whom symptomatic peripheral neuropathy was the first and only documented complication. The diagnosis of peripheral symmetrical neuropathy was based on the presence of symptoms and abnormal physical findings, confirmed with abnormal electrophysiological and/or vibratory and thermal threshold measurements. Diabetic retinopathy and nephropathy were absent. We conclude that in some type 1 insulin-dependent diabetic patients, similar to what has been reported in type 2 non-insulin-dependent diabetes, peripheral neuropathy may be the first chronic complication to become manifest. This observation provides additional evidence to suggest that each of the diabetic complications may have a different pathogenic mechanism.

Adult↗

Insulin resistance and diabetes, mechanism and possible intervention.

The issue of the peripheral resistance to insulin action has been getting a lot of attention over the last decade. The reason for this is that insulin is a major regulatory hormone and is involved in the metabolism of carbohydrates, lipids, protein and ions. To understand the pathophysiology of insulin resistance it is necessary to elucidate the methods for the assessment of insulin resistance and the molecular mechanism of insulin action. Insulin action is impaired in pathologic and physiologic states such as diabetes mellitus and obesity as well as in some rare syndromes. Further understanding of the pathophysiology of the impaired action of insulin improves the chances of defining new ways of treatment to improve the sensitivity to insulin action.

Diabetes Mellitus↗

Early pregnancy glycosylated hemoglobin, severity of diabetes, and fetal malformations.

Total percent glycosylated hemoglobin (A1a + b + c) was measured before 16 weeks' gestation in 105 insulin-treated diabetic women enrolled for prenatal care at Parkland Memorial Hospital. Seventy-three of the infants were normal, 14 had malformations, and there were 18 spontaneous abortions. The mean glycosylated hemoglobin level for the entire study group was 9.2%, compared with 9.4% for those pregnancies ending in abortion, 8.9% for those resulting in normal infants, and 10.3% when malformations occurred. The mean glycosylated hemoglobin value for women delivered of normal infants was significantly lower than the mean of those with malformed infants. Ten of the 14 malformations occurred in mothers whose early pregnancy values exceeded the mean of the entire study group. There was also an association between malformations and White classification of maternal diabetes since 10 of the 14 fetal anomalies occurred in women assigned to White Classes C, D, F, H, and R. When the distribution of malformations was analyzed according to both glycosylated hemoglobin level and White Class, there was evidence of an interaction to suggest that hyperglycemia increases the relative risk of fetal malformations when associated with maternal diabetes of longer duration and or with vascular complications.

Abortion, Spontaneous↗

Continuous subcutaneous insulin infusion during pregnancy.

The development of battery-powered pumps for continuous subcutaneous insulin infusion added new dimensions to control of diabetes during pregnancy. In this report, we describe our experiences with 28 pregnant diabetic women offered participation in an insulin pump program. Fifteen (54%) accepted pump therapy and ten continued usage during their pregnancies. Excluding abortions, eight women continuing pump use are compared to 11 others who declined such therapy and were treated with conventional methods. Although these two groups are small and not strictly comparable, the experiences now reported provide clinical insights into the application of this new technology during pregnancy. Women who successfully used insulin pumps were typically from the private sector and in better glucose control at study entry. The degree of control during pregnancy in women using pumps was not significantly different compared to conventional glucose control methods (mean glucose 120 mg/dl and 142 mg/dl, respectively). Similarly, several indices of pregnancy outcome including length of hospitalization, costs, and perinatal morbidity associated with diabetes were analyzed and no significant differences were observed. We conclude that insulin pumps are not acceptable to all pregnant diabetic women and that such therapy may not necessarily improve pregnancy outcome.

Abortion, Spontaneous↗

Improved diabetes control reduces skeletal muscle capillary basement membrane width in insulin-dependent diabetes mellitus.

We studied the relationship between the control of blood glucose and the width of skeletal muscle capillary basement membrane in 54 insulin-dependent diabetic patients. After initial measurement of levels of glycosylated hemoglobin and the width of skeletal muscle capillary basement membrane, the patients were divided into two groups: an intensive treatment group of 30 patients who were treated with continuous subcutaneous insulin infusion and a control group of 24 patients who continued to receive conventional treatment, usually two daily injections of insulin. Both groups have been followed prospectively for periods of time up to 4 years. Within 1 year the intensive treatment group had a significant decrease in glycosylated hemoglobin levels as compared to baseline values reflecting improved control of blood glucose. This level of glycosylated hemoglobin was stable over the remainder of the follow-up period. This group also had a significant reduction in the width of skeletal muscle capillary basement membrane within 1 year and it persisted for the 4 years of observation. The control group of patients had no significant change in their level of glycosylated hemoglobin and the width of the skeletal muscle capillary basement membrane tended to increase with time. It this result in skeletal muscle capillaries applies to those of retinal and renal tissue, meticulous diabetic control for a prolonged period of time may be beneficial in preventing the progression of the microvascular complications of diabetes mellitus.

Adult↗

Cryopreserved human fetal pancreas: a source of insulin-producing tissue?

Human fetal pancreata (HFP) were obtained from dilatation and extraction aborted fetuses of 11-18 weeks' gestation. The pancreas was excised under sterile conditions and kept in culture medium at 4 degrees C, prior to stepwise digestion into 50- to 150-micron fragments. The fragmented pieces were allowed to sediment by gravity, then transferred to tissue culture for 24-48 h, and cryopreserved. The freeze-thaw protocol used stepwise equilibration with dimethyl sulfoxide, nucleation of the sample at -10 degrees C, and a slow cooling rate of 0.25 degrees C/min to -40 degrees C, followed by submersion in liquid nitrogen (-196 degrees C). Rapid thawing at 300 degrees C/min from -196 degrees C was employed. Both fresh and frozen-thawed HFP fragments appeared viable as judged by light and electron microscopy, and secreted insulin in a perifusion system upon stimulation with glucose (28 mM) and theophylline (10 mM) or glucose (2.8 mM) and theophylline (10 mM). Six patients with Type I insulin-dependent diabetes mellitus, already requiring immunosuppression for a kidney transplant, had intraportal injection of 20 cryopreserved-thawed and pooled HFP fragments. Up to the 1-year post-transplant follow-up, there has been no evidence of in vivo insulin or C-peptide production. The usefulness of cryopreserved human fetal pancreata as a source of insulin-producing tissue for diabetic patients, therefore, remains to be demonstrated.

Abortion, Spontaneous↗

Relationship between lipoprotein levels and in vivo insulin action in normal young white men.

In epidemiologic studies, hyperinsulinemia has been found to be an independent risk factor for coronary heart disease (CHD). However, the mechanisms responsible for its role in atherogenesis remain unclear. We studied the relationship of in vivo insulin action and plasma lipids and lipoproteins in 44 normotriglyceridemic white men (aged 18 to 34 years). The euglycemic, hyperinsulinemic glucose clamp technique was used to quantitate insulin-mediated glucose disposal (M/I value) at a plasma insulin concentration of approximately 100 microU/mL. The M/I value correlated negatively with plasma triglycerides (r = -0.553, P less than .0001), as well as with fasting plasma insulin levels (r = -0.483, P less than .001), independent of age, body mass index, and fasting plasma glucose levels. A negative correlation of the M/I value was also observed with very low density lipoprotein (VLDL)-cholesterol (r = -0.347, P less than .05), VLDL-triglycerides (r = -0.474, P less than 0.005), and total cholesterol/high density lipoprotein (HDL)-cholesterol ratio (r = -0.431, P less than .01). The relationship between the M/I value and the total cholesterol/HDL-cholesterol ratio was independent of VLDL-cholesterol and VLDL-triglycerides, however, not independent of plasma triglycerides. No relationship was observed between insulin-mediated glucose uptake and total cholesterol, low density lipoprotein (LDL)-cholesterol, and HDL-cholesterol values. Individual differences in plasma triglycerides, fasting insulin concentration, and the total cholesterol/HDL-cholesterol ratio accounted for about half the variance observed in the M/I value.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of intensive diabetes treatment on low-density lipoprotein apolipoprotein B kinetics in type I diabetes.

The metabolism of low-density lipoprotein (LDL) was studied in six insulin-dependent (type I) diabetic patients during a 7-wk period of conventional and intensive therapy with insulin. Plasma glucose and HbA1c were normalized, demonstrating the effectiveness of our intensive treatment program. Plasma lipoprotein profiles and LDL apolipoprotein B kinetic parameters were estimated during conventional and then during intensive therapy for each patient. Intensive therapy resulted in a significant reduction of plasma and LDL cholesterol and an increase in high-density lipoprotein (HDL) cholesterol. The lower LDL levels resulted from a decreased production of lipoprotein rather than an increased fractional catabolic rate. These results are consistent with our previous observations of very-low-density lipoprotein (VLDL) metabolism during intensive therapy. VLDL production is significantly reduced; thus, a decreased production of LDL supports the contention that intensive therapy with insulin in normolipemic type I diabetic patients reduces the production of lipoproteins containing apolipoprotein B rather than increasing the clearance, and therapy also increases HDL cholesterol. Both of these effects may be beneficial in reducing the risk for coronary heart disease in type I diabetes.

Adolescent↗

Hypertension in diabetes mellitus.

Hypertension, commonly associated with diabetes mellitus, plays a major role in the severity and progression of diabetic complications. The frequency and impact of hypertension on the course of diabetic nephropathy, and the role of persistent microalbuminuria either as a predictor of future overt diabetic nephropathy or as a marker of incipient hypertension is reviewed. The special considerations for antihypertensive agents in diabetes as well as the rationale for early intervention using a "substitution" rather than "stepped-care" approach are discussed.

Albuminuria↗

Conversion from low-dose insulin therapy to glipizide in patients with non-insulin-dependent diabetes mellitus.

This study examines the effect of glipizide therapy in patients with non-insulin-dependent diabetes mellitus (NIDDM) previously treated with a low-dose insulin regimen. To determine the comparative safety and efficacy of these two treatment regimens, 135 patients with NIDDM who received low-dose insulin (40 units per day or less) were enrolled in a prospective, multicenter trial. After a four-week period of continued insulin therapy, therapy was converted to the second-generation oral sulfonylurea, glipizide. This report includes efficacy data on 79 patients with NIDDM who completed an eight- to 10-week course of glipizide therapy. A majority of these patients were obese (more than 120 percent of ideal body weight), with a mean age of 61.4 years, and a mean duration of diabetes of 10.0 years. Conversion from low-dose insulin resulted in no deterioration in overall glycemic control as reflected by an unchanged glycosylated hemoglobin at 16 weeks. Seventy patients (89 percent) attained fair glucose control and continued an additional 12 weeks of glipizide maintenance therapy. Subgroup analysis by fasting plasma glucose criteria demonstrated that 44 percent of these patients had statistically significant improvements in glucose control with glipizide as compared with insulin therapy. As this study showed, many patients with NIDDM currently receiving treatment with low-dose insulin can have maintained and some even improved glucose and lipid parameters when therapy is converted to glipizide. The rate of hypoglycemic adverse reactions corrected for duration of treatment in all 135 patients was 0.32 event per patient-month of therapy with insulin as compared with 0.12 event per patient-month of therapy with glipizide. When issues of efficacy, safety, and convenience are considered, it might be more appropriate to administer an oral sulfonylurea to patients with NIDDM rather than proceeding to therapy with insulin.

Adult↗

Monocyte-T lymphocyte interaction for regulation of insulin receptors of the activated T lymphocyte.

During activation the lymphocyte attains functional insulin receptors with precise regulation, a consequence of insulin concentration manipulations. These studies test the hypothesis that insulin receptor (+) monocytes monitor insulin concentrations, so instructing the T lymphocytes. Monocyte-enriched populations were incubated with insulin (0-10(-6) M) followed by co-culture with T lymphocytes and an activating stimulus. A dose-related fall in T lymphocyte insulin receptor binding was observed that was specific for the monocyte as the signalling cell and for insulin as the signal received. Monocytes from normal volunteers during a euglycemic, hyperinsulinemic clamp were cultured with T lymphocytes and an activating stimulus. A decline in specific insulin receptor binding on T lymphocytes was observed, which Scatchard analysis demonstrated to be a consequence of reduction in receptor numbers. These studies demonstrate that the receptor (+) monocyte perceives the concentration of insulin and passes this information to T lymphocytes regulating the number of activation-induced insulin receptors. The interplay between the monocyte and T lymphocyte parallels the interaction of these cell types for recognition of antigen.

Animals↗

Rapid decrease of insulin-specific IgG antibody levels in insulin-dependent patients transferred to semi-synthetic human insulin.

A multicenter, open trial was designed to examine the efficacy and safety of semi-synthetic human insulin (SSHI; Novolin R and Novolin L, SQUIBB-NOVO) in patients with insulin-dependent diabetes mellitus who were transferred from other commercially-available insulins. Whether such a change in therapy would reduce circulating IgG antibodies to antibovine insulin was also evaluated. A total of 68 males and females, 8-62 yr of age, were maintained on their original insulin therapy for 4 weeks, when both glycosylated hemoglobin and fasting blood glucose were assessed. IgG antibody titers to antibovine insulin were also measured. All patients were then transferred to SSHI for a period of 20 weeks. The same variables were evaluated at Weeks 2, 4, 8, and 20. Mean fasting blood glucose levels rose monotonically from 189-226.3 mg/dl over the course of the 20-week clinical trial. There was a slight but insignificant increase in glycosylated hemoglobin by the end of the test period. The average value for antibovine insulin IgG antibodies decreased from 2.54 mu/ml at baseline to 1.32 mu/ml by the completion of the trial. Significant decreases were first observed 4 weeks after the patients were placed on SSHI therapy. After transfer to SSHI, 43.3% of the patients achieved some improvement in glycemic control and only 16.4% were worse than at baseline. A decrease in weekly hypoglycemic reactions occurred during the course of the SSHI therapy. It appears that SSHI provides safe and effective treatment for insulin-dependent diabetic patients and that its use results in a rapid and significant decrease in insulin antibody formation.

Adult↗

Retinal microaneurysm counts in diabetic retinopathy: colour photography versus fluorescein angiography.

Microaneurysms were counted separately in a masked manner on stereo colour fundus photographs and on stereo fluorescein angiograms of 100 patients with unselected forms of diabetic retinopathy. Serial studies obtained 6 months apart were available for most patients, and a total of 315 separate photographic studies were evaluated. In addition, 118 photographic studies of 38 young patients with type I diabetes mellitus were evaluated. About twice as many microaneurysms were detected on the fluorescein angiograms as on the colour photographs for both groups of patients (p less than 0.05). Fluorescein angiography showed microaneurysms in 57% of the eyes in the second group photographed for the first time that had no detectable microaneurysms on colour photography. The use of fluorescein angiography is recommended in diabetic patients when detection of subtle microvascular abnormalities is deemed essential.

Aneurysm↗