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Biomedical subjects

D A Skor

Publications and source records attributed to D A Skor.

8 recordsLinked to original sources
PubMed1985

Insulin clearance contributes to the variability of nocturnal insulin requirement in insulin-dependent diabetes mellitus.

We have previously described, in insulin-dependent diabetic subjects (IDDM), a small, but significant, increase in the insulin clearance rate (ICR) during 0600-0800 h as compared with 0100-0300 h. To determine whether this increase was also seen at more physiologic levels of insulin replacement, we calculated ICR during euglycemic clamp studies in 13 patients with IDDM with a constant infusion of insulin at 20 mU/min/m2 and during insulin replacement from the Biostator GCIIS without exogenous glucose. During the euglycemic clamp study with constant insulin infusion at 20 mU/min/m2, the ICR was 16% higher at 0600-0800 h than at 0100-0300 h (264 +/- 50 ml/min/m2 versus 228 +/- 51 ml/min/m2; P less than 0.005). During insulin replacement by the Biostator, the mean insulin infusion rate increased by 92 +/- 27% (7.5 +/- 1.1 to 13.5 +/- 1.2 mU/min/m2; P less than 0.001) and ICR increased by 123 +/- 30% (130 +/- 24 to 268 +/- 51 ml/min/m2; P less than 0.01) during the prebreakfast period when compared with 0100-0300 h. There was a highly significant correlation (r = 0.97) between the increment in insulin infusion rate and the increment in ICR. Measurement of insulin concentration in saline solutions, delivered by the Biostator at a same rate and under similar conditions to those in this study, showed that insulin delivery was stable for the 8-h period of this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Influence of growth hormone on overnight insulin requirements in insulin-dependent diabetes.

After a 0100-0300 h nadir, the insulin requirements to maintain blood glucose at 90-110 mg/dl increase substantially in the prebreakfast (0600-0800 h) period in some insulin-dependent diabetic patients (IDDMs). Early insulin-like and delayed insulin-antagonistic effects of physiologic early morning increases in growth hormone (hGH) secretion may account for this variability of overnight insulin requirements. To assess the role of hGH, we studied five IDDMs using a closed-loop insulin infusion device (Biostator, GCIIS). Either saline (C) or somatostatin plus glucagon (SRIF + G) was infused during separate overnight (2400-0800 h) study periods. An infusion of hGH from 2400 to 0130 h was added to SRIF + G infusion during an additional study period (SRIF + G + hGH). In comparison to 0100-0300 h, mean insulin infusion rates required to maintain blood glucose values between 105 and 120 mg/dl during the prebreakfast period increased by 66 +/- 25% during C, and 42 +/- 12% during SRIF + G when serum growth hormone was suppressed to less than or equal to 0.75 ng/ml. During SRIF + G + hGH, the mean prebreakfast insulin infusion rate increased by 42 +/- 11% with a mean peak hGH level of 14.7 +/- 5.4 ng/ml at 0130 h. Mean plasma free insulin levels remained constant during the night despite the significantly higher insulin infusion rates between 0600 and 0800 h. During SRIF + G, insulin requirements remained constant overnight before 0600 h, whereas during both C and SRIF + G + hGH conditions, a nadir was noted between 0100 and 0300 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Defective glucose counterregulation limits intensive therapy of diabetes mellitus.

Defective recovery from insulin-induced hypoglycemia, due to combined deficiencies of glucagon and epinephrine secretory responses to plasma glucose decrements, occurs in some patients with insulin-dependent diabetes mellitus (IDDM). Patients with IDDM determined to have inadequate glucose counterregulation during an insulin infusion test (40 mU X kg-1 X h-1) with bedside plasma glucose monitoring and clinical observation have been found to have a 25-fold greater risk of severe hypoglycemia during subsequent intensive therapy than patients with adequate glucose counterregulation. Thus, the efficacy of the glucose counterregulatory systems determines the limits of intensive therapy of IDDM.

Blood Glucose↗
PubMed1984

Relative roles of insulin clearance and insulin sensitivity in the prebreakfast increase in insulin requirements in insulin-dependent diabetic patients.

During continuous subcutaneous or intravenous insulin infusion therapy, many patients with insulin-dependent diabetes (IDD) require more insulin in the prebreakfast period (0600-0800 h) than earlier in the morning (0100-0300 h). This study was designed to assess whether variations in insulin clearance or insulin sensitivity might contribute to overnight variations in insulin requirements. Euglycemic insulin clamp studies were performed in random sequence from 2400 to 0300 h and from 0500 to 0800 h on successive nights in 10 subjects with IDD. Insulin was infused at a rate of 40 mU/min/m2 and plasma glucose concentration was maintained at 100 mg/dl by a variable rate glucose infusion from a Biostator GCIIS (Miles Laboratories, Elkhart, Indiana). Insulin clearance was (mean +/- SEM) 277 +/- 41 ml/min/m2 between 0700 and 0800 h compared with 256 +/- 41 ml/min/m2 between 0200 and 0300 h (P less than 0.05), while glucose infusion rates were the same [3.86 +/- 0.52 mg/kg/min from 0730 to 0800 h versus 3.99 +/- 0.51 mg/kg/min from 0230 to 0300 h (P = NS)]. All eight patients with a previously documented prebreakfast increase in insulin requirements had higher insulin clearance at this time. These results indicate that differences in insulin clearance between the prebreakfast period and the early morning may account partially for the higher prebreakfast insulin requirements in some subjects with IDD, and the variations in insulin requirements during the night are not due to variations in insulin sensitivity.

Adult↗
PubMed1983

Identification of type I diabetic patients at increased risk for hypoglycemia during intensive therapy.

During intravenous insulin infusions (40 mU per kilogram of body weight per hour for up to 100 minutes), 9 of 22 patients with insulin-requiring diabetes mellitus had neurologic signs or symptoms of hypoglycemia, plasma glucose concentrations that were below 35 mg per deciliter (1.9 mmol per liter) and continued to decline, or both. This inadequate glucose counterregulation resulted from the combined effect of deficient glucagon and epinephrine responses. In 8 of the 9 patients with inadequate counterregulation severe hypoglycemia developed during subsequent intensive therapy, whereas such episodes occurred in only 1 of 13 patients with adequate counterregulation. Thus, an intravenous insulin-infusion test can prospectively identify patients who are at increased risk for recurrent severe hypoglycemia during intensive therapy for diabetes.

Adolescent↗
PubMed1983

Examination of the role of the pituitary-adrenocortical axis, counterregulatory hormones, and insulin clearance in variable nocturnal insulin requirements in insulin-dependent diabetes.

In insulin-dependent diabetics, insulin requirements increase significantly after 0600 h, resulting in prebreakfast hyperglycemia with either conventional insulin therapy or constant insulin infusions with insulin infusion devices. In order to clarify the role of the pituitary-adrenocortical axis and further examine the mechanisms of the phenomenon of nocturnal variability in insulin requirements, we studied five IDDs using a closed-loop insulin infusion device (Biostator, GCIIS). The subjects were given saline (SAL) or dexamethasone (DEX) i.v. from 1800 to 0900 h on successive nights. From 2400-0300 to 0600-0900 h, mean insulin infusion rates required to maintain blood glucose values between 109 and 120 mg/dl increased by 0.21 +/- 0.05 mU/kg/min during the SAL infusion, and 0.16 +/- 0.04 mU/kg/min during the DEX infusion, when plasma cortisols were suppressed to less than or equal to 2 micrograms/dl. Mean free insulin concentrations did not increase and remained constant throughout both study nights in spite of the significantly higher 0600-0900-h insulin infusion rates. Growth hormone, glucagon, epinephrine, and norepinephrine concentrations showed normal nocturnal and early morning patterns during both study nights. We conclude that the nocturnal variability in insulin requirements persists despite suppression of the pituitary-adrenocortical axis, and that increased free insulin clearance or degradation may contribute to the "dawn phenomenon" of rising prebreakfast glucose despite constant insulin infusion.

Adult↗