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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The absorption kinetics of human insulin (Novo) were studied and compared with those of purified porcine insulin preparations in seven healthy men. The absorption of insulin after subcutaneous injection of human insulin (Actrapid, Novo) was significantly accelerated and its hypoglycemic effect significantly stronger when compared with porcine insulin (Actrapid). No differences in the absorption kinetics were observed using human insulin (Monotard, Novo) and porcine insulin (Monotard) preparations, respectively. A clinical trial was designed to determine whether the pharmacokinetic differences were relevant for the clinical use of regular human insulin. The efficacy of human and porcine insulin (Actrapid) was tested in a double-blind crossover protocol in 12 type I diabetic patients treated with continuous subcutaneous insulin infusion. Near-normoglycemia was achieved with both types of insulin. Diurnal blood glucose values and excursions, insulin requirements, the frequency of mild hypoglycemic episodes, and the carbohydrate content of the diet were essentially identical. Thus, the differences between the absorption of human insulin and porcine regular insulin from a subcutaneous depot as observed in the pharmacokinetic studies in normal man do not appear to be relevant in the clinical practice of the subcutaneous insulin replacement therapy in type I diabetes mellitus at near-normoglycemia.
Diabetes Care
PMID:Subcutaneous use of regular human insulin (Novo): pharmacokinetics and continuous insulin infusion therapy. 634 35

Diurnal concentrations of glucose, the major regulatory hormones, and selected biochemistries were measured serially throughout a 25-h period in 38 healthy type I diabetic patients, 25 patients with acute ketoacidosis, and 20 normal subjects. Poor glucose control, meal intolerance, and hypercortisolemia were the dominant abnormalities in the healthy diabetic subjects. Ketonemia due to elevated plasma beta-hydroxybutyrate concentrations without ketonuria (nitroprusside reaction) was a frequent finding in a group of poorly controlled diabetic subjects. In the patients with acute ketoacidosis, the dominant abnormalities were overproduction of epinephrine and cortisol. High glucagon and growth hormone concentrations were documented in about one-half of these patients. We conclude that (1) the hyperglycemia, meal intolerance, and abnormal ketone body metabolism seen in these patients are caused by inadequacies in their insulin regimens; (2) ketone body underutilization contributes to diabetic ketosis; (3) epinephrine and cortisol overproduction are important components of acute ketoacidosis; and (4) the complex hormone-metabolic interactions in type I diabetes can best be explained by a multihormonal hypothesis with the primary defect being loss of beta-cell function.
Diabetes Care
PMID:Hormone and metabolic profiles in children and adolescents with type I diabetes mellitus. 682 6

Rats made diabetic with streptozotocin received a single subcutaneous implant of an insulin polymer pellet that released insulin continuously at approximately 2 U/day. Continuous normoglycemia was achieved for up to 1 mo. Mean glucose level for treated animals was 113 mg/dl as compared with 398 mg/dl for untreated diabetic controls. Diurnal blood glucose values for treated animals ranged from 71 to 116 mg/dl. Polyuria and glycosuria were corrected by the presence of the insulin + polymer. Treated animals gained weight normally and reached a mean weight of 350 g, whereas untreated control animals lost weight, to a mean of 150 g. When insulin + polymer preparations were periodically implanted and removed at 7-day intervals, normoglycemia was only associated with the presence of implants.
Diabetes 1980 Jan
PMID:One month of sustained release of insulin from a polymer implant. 699 15

Diurnal profiles of total and lipoprotein cholesterol and triglycerides were measured in 11 insulin-dependent diabetic subjects without retinopathy, 10 with background and 10 with proliferative retinopathy. The groups were closely matched for age and duration of diabetes. Total cholesterol levels were higher in patients with proliferative (5.6 +/- 0.5 mmol/l) than background (5.1 +/- 0.7 mmol/l) or no retinopathy (4.6 +/- 0.8 mmol/l, trend test; p less than 0.003), due to raised levels of low density lipoprotein (LDL) cholesterol (3.8 +/- 0.9, 3.2 +/- 0.6 and 2.8 +/- 0.8 mmol/l respectively; p less than 0.02). High density lipoprotein (HDL) levels were similar in patients with and without retinopathy and HDL/LDL ratios were lower with more severe retinopathy (p less than 0.025). Cholesterol levels were similar in diabetic subjects without retinopathy and in 12 normal subjects. Triglyceride levels were not related to retinopathy and no measure of plasma lipids correlated with HbA1 or 24-h mean plasma glucose. Total and LDL cholesterol were weakly inversely correlated with creatinine clearance but the association with retinopathy was independent of this effect.
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PMID:Low density lipoprotein cholesterol: an association with the severity of diabetic retinopathy. 704 26

A randomized prospective study was conducted to determine whether the insulin regimen for NIDDM subjects poorly controlled on oral therapy should be designed primarily to control basal metabolism or to control mealtime hyperglycaemia. Grossly obese subjects were excluded. After a 2-month run-in phase involving intensive education, subjects were randomized to therapy with twice daily isophane or three times daily soluble insulin. Both Protaphane and Actrapid brought about similar improvement in HbA1 (9.5 +/- 0.5 and 9.7 +/- 0.4%) compared with baseline (11.7 +/- 0.5%; p < 0.001). Diurnal blood glucose profiles showed that despite the good post-prandial control achieved by pre-meal soluble insulin, loss of control occurred overnight, resulting in higher fasting blood glucose levels compared with Protaphane therapy (8.0 +/- 0.8 vs 10.6 +/- 0.8 mmol l-1; p < 0.05). The overall rate of hypoglycaemia was 0.44 patient-1 year-1. Thirty-two mild hypoglycaemic episodes occurred on Protaphane therapy and 79 on Actrapid therapy. Using formal psychometric tests it was shown that insulin therapy was associated with improved treatment satisfaction and that this was greater on Protaphane therapy (p < 0.05). Overall well-being increased similarly in the two groups. All subjects wished to continue with insulin therapy after the conclusion of the study. The insulin regimen for moderately or poorly controlled non-insulin-dependent diabetes should primarily be designed to correct the basal insulin deficiency rather than to mimic normal meal-induced insulin secretion.
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PMID:Insulin regimens for the non-insulin dependent: impact on diurnal metabolic state and quality of life. 795 71

Autonomic heart rate control was assessed by power spectral analysis of heart rate variability in 24-hour ambulatory electrocardiographic recordings from 23 healthy subjects, 14 patients with coronary artery disease without cardiac dysfunction, and 14 patients with diabetes mellitus. The log value of the ratio of the low-frequency component (LF = 0.04 to 0.15 Hz) to the high-frequency component (HF = 0.15 to 0.5 Hz) and logHF were employed as indexes of sympathetic and parasympathetic activity, respectively. Diurnal and nocturnal logLF, logHF, and log(LF/HF) values were calculated for heart rates of 60, 70, and 80 beats/min. Intergroup differences among these three variables were not significant at any heart rate. Although a heart rate-related decrease in logHF was generally observed, the relationship between log(LF/HF) and heart rate was not consistent. The correlation between diurnal and nocturnal logHF values was significant at all three heart rates (r = 0.63, 0.87, and 0.59), whereas the diurnal log(LF/HF) was correlated with the nocturnal value only at 70 beats/min (r = 0.77). These results suggest that the heart rate during normal daily activities is a reliable indicator of parasympathetic tone, if not sympathetic tone, in healthy subjects and patients with coronary artery disease or diabetes mellitus.
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PMID:Parasympathetic activity is a major modulator of the circadian variability of heart rate in healthy subjects and in patients with coronary artery disease or diabetes mellitus. 832 51

The urinary albumin excretion rate (AER) in a subgroup of patients with insulin-dependent diabetes mellitus (IDDM) steadily increases. In these patients a concomitant reduction of the glomerular charge selectivity index (SI) has been demonstrated. The aim of the present study was to evaluate whether diurnal variation in AER could be related to a diurnal variation in SI and/or a diurnal blood pressure variation. Thirty-three patients with IDDM, 27 with normal albumin excretion (AER < 20 micrograms/min; group D(o)) and six with incipient nephropathy (AER from 20 to 200 micrograms/min; group DA), were studied. AER and SI (renal clearance ratio of total-IgG/IgG4) were measured in three different urine collecting periods: period A (8:00 a.m. to 12:00 a.m.), period B (12:00 a.m. to bedtime) and period C (bedtime to 8:00 a.m.). A significant increase in SI was seen during the nighttime: period A, 1.6 (0.2 to 3.8; mean, range); period B, 1.7 (0.3 to 3.0); and period C, 2.0 (0.2 to 4.0); P = 0.01. Corresponding to this observation, an overall significant decrease in AER was found: period A, 10 (3 to 137) micrograms/min (median, range); period B, 8 (3 to 84) micrograms/min; and period C, 5 (0 to 78) micrograms/min; P < 0.001. In all three sampling periods a negative correlation was found between AER and SI. When group D(o) was analyzed alone, the results were similar. Diurnal variation in blood pressure was significantly positively correlated with AER in group DA, but was not correlated to variation in AER in D(o). We suggest that in normoalbuminuric IDDM patients diurnal variation in AER is related to diurnal variation in SI.
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PMID:Diurnal variation in glomerular charge selectivity, urinary albumin excretion and blood pressure in insulin-dependent diabetic patients. 854 14

Diurnal variation in insulin sensitivity in patients with NIDDM has long been suspected but has been difficult to document mainly because of the interdependence of changes in glucose and insulin. Stable serum insulin levels during hyperglycemic clamping in patients with NIDDM in the present study provided the opportunity to examine changes in insulin sensitivity unaffected by changes in blood glucose and insulin concentrations. Six patients with NIDDM (four men and two women, BMI 33.9 +/- 2.5) underwent hyperglycemic (11.1 mmol/l, approximately 200 mg/dl) clamping for 72 h. Measured were serum insulin, free fatty acid (FFA), cortisol, and growth hormone concentrations and rates of insulin secretion, insulin clearance, and glucose infusion rate (GIR) needed to maintain hyperglycemia. In addition, five patients (three men and two women, BMI 32.6 +/- 0.6) underwent hyperglycemic clamping for 24 h with hourly determinations of hepatic glucose production (HGP) and glucose disappearance rates (GRd). GIR, reflecting insulin sensitivity, changed rhythmically with a cycle duration of 22.9 +/- 1.4 h and an amplitude of 47.8 +/- 11.2%. GIR was lowest at 8:31 a.m. (+/- 52 min) and highest at 7:04 p.m. (+/- 58 min). Circadian changes in GIR were completely accounted for by changes in HGP, while GRd remained unchanged. Plasma levels of FFAs and cortisol also exhibited circadian fluctuations, and their blood levels correlated negatively with GIR (r = -0.72 and -0.64, respectively). We concluded that insulin sensitivity in patients with NIDDM changed with circadian (approximately 24 h) rhythmicity (decreasing during the night and increasing during the day). These changes were unrelated to blood levels of glucose and insulin, insulin clearance, exercise, food intake, and sleep. They were caused by circadian changes in HGP, which in turn were closely correlated with circadian changes in blood FFA and cortisol levels. We believe that recognition of these circadian changes has implications for the diagnosis and the treatment of patients with NIDDM.
Diabetes 1996 Aug
PMID:Evidence for a circadian rhythm of insulin sensitivity in patients with NIDDM caused by cyclic changes in hepatic glucose production. 869 Jan 50

To clarify the precise function of incidentally discovered adrenocortical adenoma, immunohistochemical and dispersed adrenal cell studies were performed. We have recently seen five patients with so-called nonfunctioning adrenocortical adenoma. Diurnal variation in plasma cortisol and suppression of plasma cortisol and urine 17-hydroxycorticosteroids in response to dexamethasone administration revealed adrenocortical function within normal limits in all cases, and no signs or symptoms of adrenal steroid hormone excess were evident. Since a high uptake of iodomethylnorcholesterol was recognized in each adrenal mass, it was supposed that these adrenal tumors produced steroid hormone to a certain extent, and each patient received unilateral adrenalectomy. P450c17, a key enzyme involved in cortisol production, was expressed in the tumor region in all cases in an immunohistochemical study. Upon in vitro steroidogenesis with dispersed adrenal cells in two cases, all steroid hormones measured except for aldosterone (progesterone, 17 alpha-hydroxyprogesterone, pregnenolone, 17 alpha-hydroxypregnenolone, 11-deoxycortisol, cortisol, 11-deoxycorticosterone, corticosterone, 18-hydroxydeoxycorticosterone, dehydroepiandrosterone and androstenedione) were produced in a culture medium. The results indicated that these tumors possessed the capacity for cortisol production, which was in agreement with the results of an iodomethyl-norcholesterol scintigraphy. All patients with mild hypertension or diabetes mellitus had no signs or symptoms of steroid hormone excess, but they could potentially develop a steroid excess syndrome such as Cushing's syndrome in the future.
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PMID:Incidentally discovered adrenocortical adenomas are not fully nonfunctioning: immunohistochemical and dispersed adrenocortical cell study. 873 56

Consistent variations in glucose regulation across the 24-hour cycle are present in normal subjects. These diurnal variations are altered in various states of impaired glucose tolerance (aging, obesity, diabetes). Changes in insulin secretion, clearance and/or action across the day have been demonstrated. Studies in subjects receiving continuous intravenous glucose infusion have shown that major alterations of glucose tolerance occur during sleep and that sleep quality markedly influences glucose utilization. Diurnal variations in glucose tolerance result from the alternation of wake and sleep states as well as from intrinsic effects of circadian rhythmicity. The important roles of physiological variations in levels of counterregulatory hormones which are markedly dependent on sleep (i.e. growth hormone) or circadian rhythmicity (i.e. cortisol) have only begun to be appreciated. The modulatory effects of sleep and circadian rhythmicity on glucose regulation may have important clinical implications for the diagnosis and treatment of abnormalities of carbohydrate metabolism.
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PMID:The roles of time of day and sleep quality in modulating glucose regulation: clinical implications. 955 Jan 24


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