Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of these studies was to compare the pharmacokinetics, pharmacodynamics, counterregulatory hormone and symptom responses, as well as cognitive function during hypoglycaemia induced by s.c. injection of 0.15 IU/kg of regular human insulin (HI) and the monomeric insulin analogue [Lys(B28),Pro (B29)] (MI) in insulin-dependent-diabetic (IDDM) subjects. In these studies glucose was infused whenever needed to prevent decreases in plasma glucose below 3 mmol/l. After MI, plasma insulin increased earlier to a peak (60 vs 90 min) which was greater than after HI (294 +/- 24 vs 255 +/- 24 pmol/l), and plasma glucose decreased earlier to a 3 mmol/l plateau (60 vs 120 min) (p < 0.05). The amount of glucose infused to prevent plasma glucose falling below 3 mmol/l was approximately three times greater after MI than HI (293 +/- 26 vs 90 +/- 25 mumol.kg-1 x 60-375 min-1, p < 0.05). After MI, hepatic glucose production was more suppressed (0.7 +/- 1 vs 5.9 +/- 0.54 mumol.kg-1.min-1) and glucose utilization was less suppressed than after HI (11.6 +/- 0.65 vs 9.1 +/- 0.11 mumol.kg-1.min-1) (p < 0.05). Similarly, plasma NEFA, glycerol, and beta-OH-butyrate were more suppressed after MI than HI (p < 0.05), whereas plasma lactate increased only after MI, but not after HI. Responses of counterregulatory hormones, symptoms and deterioration in cognitive function during plasma glucose plateau of 3 mmol/l were superimposable after MI and HI (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pharmacokinetics, pharmacodynamics and glucose counterregulation following subcutaneous injection of the monomeric insulin analogue [Lys(B28),Pro(B29)] in IDDM. 795 44

Intensive insulin therapy is frequently complicated by excessive weight gain. The purpose of this study was to determine the cause and composition of this weight gain. Therefore, changes in body composition, energy expenditure, glycosuria, and substrate kinetics were evaluated in patients with IDDM who transferred from conventional insulin therapy to intensive insulin therapy. Six adult patients with IDDM were studied on conventional insulin therapy and after 2 mo of intensive insulin therapy while maintaining constant caloric intake and were compared with a group of 6 matched nondiabetic volunteers. Body composition was determined by underwater weighing. Energy expenditure was measured during 24-h stays in a whole-room calorimeter. Whole-body turnover rates of glucose, glycerol, palmitate, and leucine were determined by isotope dilution methods. Intensive insulin therapy lowered the mean daily blood glucose concentration and HbA1 (14.8 +/- 1.6 to 7.7 +/- 0.6 mM and 12.9 +/- 0.9 to 9.6 +/- 0.6%, both P < 0.01) and almost eliminated glycosuria (428 +/- 116 to 39 +/- 22 mmol/day, P < 0.05). Body weight increased 2.6 +/- 0.8 kg with intensive insulin therapy (P < 0.05) as a result of an increase in fat mass (2.4 +/- 0.8 kg, P < 0.05). Daily energy expenditure decreased 5% (118 +/- 32 kcal/day) with intensive insulin therapy (P < 0.05). The rates of glucose, glycerol, free fatty acid, and leucine turnover, triglyceride/free fatty acid cycling, and nonoxidative glucose and protein disposal were reduced in the diabetic volunteers during intensive insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Intensive insulin therapy and weight gain in IDDM. 824 15

The insulin sensitivity of intermediary metabolism was studied in 8 non-obese men with well-controlled diet-treated non-insulin dependent diabetes (NIDDM) using a low dose incremental insulin infusion (basal, 0.005 and 0.01 U/kg h-1). Results were compared to 8 healthy male control subjects matched (NIDDM vs. controls, mean +/- S.E.M.) for age (56 +/- 3 vs. 54 +/- 3 years, NS) and body mass index (24.6 +/- 0.7 vs. 25.3 +/- 0.5 kg/m2, NS). Basal fasting concentrations of insulin (4.7 +/- 0.8 vs. 3.2 +/- 0.8 mU/l, NS), glucose, total ketone bodies (TKB), and non-esterified fatty acids (NEFA) were not significantly different between the groups but glycerol concentrations were significantly elevated in NIDDM patients (0.072 +/- 0.007 vs. 0.049 +/- 0.003 mmol/l, P < 0.05). During incremental insulin infusion, plasma insulin concentrations rose to 12.8 +/- 1.5 vs. 10.0 +/- 1.0 mU/l in NIDDM patients vs. control and metabolite concentrations fell significantly (P < 0.001). Significant linear dose-response relationships were found between plasma insulin (log) and glucose, TKB (log), NEFA, and glycerol concentrations by analysis of variance applied to regression (all P < 0.001). For glucose and TKB (log), the group regression lines were parallel but were significantly right-shifted in the NIDDM group (P < 0.001). In contrast, the relationships of insulin (log) and both glycerol and NEFA concentrations converged over the observed range of insulin concentrations. Significant displacement of glycerol and NEFA dose-response relationships were found in NIDDM patients at an insulin concentration of 5 mU/l (P < 0.001) but not at 12.5 mU/l.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Insulin resistance in the regulation of lipolysis and ketone body metabolism in non-insulin dependent diabetes is apparent at very low insulin concentrations. 834 30

To determine the etiology of euglycemic ketoacidosis, the effect of a 32-h fast on the rate of metabolic deterioration was examined in a group of 10 healthy subjects with type I diabetes mellitus. Patients were studied during 5 h of insulin withdrawal after 8 h (postprandial) and 32 h (fasted) of food deprivation. Study parameters included substrate levels, electrolytes, counterregulatory hormone levels, and rates of glucose and glycerol turnover. In the fasted state, mean peak plasma glucose concentrations were significantly lower than those in the 8-h postprandial state (13.3 +/- 1.6 vs. 17.4 +/- 1.4 mmol/L, respectively; P < 0.05), and mean rates of glucose production were also significantly lower at all time points in the fasting state. The rate of development of ketosis was significantly more rapid during insulin deficiency after a fast (8.82 +/- 0.63 vs. 6.23 +/- 0.30 micro/L.min; P < 0.05), while plasma nonesterified fatty acids and glycerol turnover showed a biphasic response to insulin withdrawal, which was also more robust after a fast. Metabolic acidosis, as reflected in the rate of decrease in serum bicarbonate concentration, was more severe after 32 h of fasting than in the postprandial state (mean nadir, 15.4 +/- 0.9 vs. 18.6 +/- 0.5 mmol/L; P < 0.001). In contrast to values in the postprandial state, serum glucagon levels rose during insulin withdrawal in the fasting state, and plasma norepinephrine levels also correlated positively with the ongoing metabolic decompensation. Other counterregulatory hormones did not differ significantly in the fasted vs. postprandial states in these short term metabolic studies. We conclude that a fast of moderate duration, such as might be expected to occur during the development of diabetic ketoacidosis, predisposes patients with type I diabetes to euglycemic ketoacidosis during periods of insulin deficiency. Furthermore, decreased rates of hepatic glucose production are responsible for the lower plasma glucose values observed during a fast. The development of ketosis continued progressively in both conditions, but the rate of rise of plasma ketones was increased in the fasted state. This accelerated development of ketosis may be attributable to the effects of elevated levels of glucagon and/or catecholamines on lipolysis.
 ...
PMID:Short-term fasting is a mechanism for the development of euglycemic ketoacidosis during periods of insulin deficiency. 849 10

Mobilization of lipids from adipose tissue during prolonged exercise is of key importance for the supply of energy to the working muscle. During exercise lipid mobilization is mainly stimulated by increased catecholamine production leading to acceleration of the beta-adrenoceptor mediated lipolysis rate in fat cells. This causes breakdown of triglycerides in fat cells to glycerol and free fatty acids, which then are delivered to the blood stream. Decreased insulin production, enhanced adipose tissue blood flow and decreased reesterification of free fatty acids in fat cells contribute to the enhancement of lipid mobilization during strenuous and long-term light exercise. Several additional factors modulate the lipolytic response to exercise as well. Endurance training increases the lipolytic action of catecholamine whereas the opposite occurs during ageing. These alterations are at least in part mediated by changes in the function of the final step in lipolysis activation, the protein kinase-hormone sensitive lipase complex. There are also gender and regional differences in the lipolytic response to exercise. Women mobilize more lipids from the subcutaneous abdominal area than men, whereas a low rate of lipid mobilization from the peripheral subcutaneous areas is observed in either sex. In pathophysiological states, which are associated with catabolism such as fasting and insulin dependent diabetes, there is an enhanced lipolytic response to exercise, because of increased beta-adrenoceptor function.
 ...
PMID:Impact of exercise on adipose tissue metabolism in humans. 858 Oct 90

To characterize its insulin-antagonistic effect, growth hormone (GH) was infused at variable rates (24, 12 or 6 mU kg-1 min-1) for 1 h in 7 IDDM patients. Saline infusion was used as control (C) and all patients participated in all studies. The effect of insulin was measured with the euglycaemic clamp technique for 6 h combined with d-(3-3H)-glucose to evaluate glucose turnover. The insulin levels during the clamps were similar in all studies (23 +/- 3 mU l-1). The infusions produced peak GH levels of (24 rate = 24) 157 +/- 11, (12 rate = 12) 76 +/- 7, and (6 rate = 6) 45 +/- 8 mU l-1 (mean +/- SEM). The insulin-antagonistic effect of GH on glucose uptake was seen after 2 h and was at a maximum 4 to 5 h after the start of the GH infusion (difference in glucose infusion rate between C and 24 was 1.7 +/- 0.4 mg kg-1 min-1, p < 0.01). The resistance was due to a less pronounced effect of insulin to both inhibit rate of appearance and to stimulate rate of disappearance. Infusion of GH at 12 mU kg-1 min-1 induced a less pronounced insulin resistance both with regards to maximal effect (glucose infusion rate C - GH 1.4 +/- 0.5 mg kg-1 min-1, p < 0.05) and duration (3 h). At 6 mU kg-1 min-1, a clear GH-induced insulin-antagonistic effect was only seen during the third hour of the clamp (glucose infusion rate C-GH 1.3 +/- 0.5 mg kg-1 min-1, p < 0.05). GH infusion impaired the effect of insulin to lower both the levels of free fatty acids (NEFA) and glycerol between 2 and 5 h after the start of the infusion (NEFA, C:110 +/- 29, 24:303 +/- 95, p < 0.05: glycerol, C:32 +/- 4, 24:50 +/- 7 mumol l-1, p < 0.05). The present study therefore demonstrates that the insulin-antagonistic effect of GH in IDDM is related to the plasma levels both with regard to duration and response. The results also indicate that GH impairs the effect of insulin on lipolysis in IDDM after physiological peaks.
 ...
PMID:Characterization of the insulin-antagonistic effect of growth hormone in insulin-dependent diabetes mellitus. 858 32

The adrenergic regulation of adipose tissue lipolysis in response to insulin-induced hypoglycaemia (intravenous infusion of soluble insulin 0.10 IU.kg body weight-1.h-1 until the arterial plasma glucose fell below 2.8 mmol/l) was investigated directly in vivo in 11 insulin-dependent diabetic (IDDM) patients and 12 control subjects, using microdialysis of the extracellular space of abdominal subcutaneous adipose tissue. The tissue glycerol level (lipolysis index) and the escape of ethanol from the perfusion medium (blood flow index) were continuously monitored. During insulin infusion the arterial glucose level was reduced in parallel and the hypoglycaemic nadir was almost identical in the two groups (diabetic patients 2.2 +/- 0.1 and control subjects 2.3 +/- 0.1 mmol/l). While the maximum response of plasma epinephrine to hypoglycaemia was 30% lower in diabetic patients than in the control subjects (p < 0.05), the glycerol levels in adipose tissue and in plasma, as well as in serum non-esterified fatty acids, increased twice as much in the former as in the latter group following hypoglycaemia (p < 0.01). Addition of the beta-adrenoceptor blocker propranolol (10(4) mol/l) to the tissue perfusate almost completely prevented the hypoglycaemia-induced increase in the adipose tissue glycerol level in both groups, whereas in situ perfusion with 10(-4) mol/l of the alpha-adrenoceptor blocker phentolamine resulted in an additional increase in the tissue glycerol levels; during alpha-blockade, the glycerol response to hypoglycaemia remained enhanced by threefold in the diabetic patients (p < 0.01). In both groups local adipose tissue blood flow increased transiently in a similar way after hypoglycaemia; the increase being inhibited by in situ beta-adrenoceptor blockade. We conclude that both alpha- and beta-adrenergic mechanisms regulate adipose tissue lipolysis in response to hypoglycaemia. In IDDM, lipolysis is markedly enhanced following hypoglycaemia, despite a reduced catecholamine secretory response, because of increased beta-adrenoceptor action in adipose tissue.
 ...
PMID:Stimulation of adipose tissue lipolysis following insulin-induced hypoglycaemia: evidence of increased beta-adrenoceptor-mediated lipolytic response in IDDM. 881 10

It is not clear how circadian lipolysis and circulating concentrations of non-esterified fatty acids (NEFA) are altered in intensively treated insulin-dependent diabetic (IDDM) patients. Ten IDDM patients on an intensive insulin regimen and eight healthy control subjects were investigated under ordinary living conditions for 27 h by microdialysis of subcutaneous adipose tissue. The true tissue glycerol concentration and adipose blood flow changes were monitored as an index of lipolysis. A circadian pattern in adipose tissue lipolysis was observed in both groups, decreasing during the day and increasing during evening-night. The daytime decrease was normal, but the evening-night rise was elevated in IDDM (p = 0.03). Circulating NEFA decreased during the day and increased at night. The latter increase was enhanced threefold in IDDM (p = 0.003) and correlated with fasting glucose levels (r = 0.77). Nocturnal growth hormone (GH) was increased fivefold in IDDM and correlated to nocturnal lipolysis (r = 0.83). Adipose tissue blood flow increased during the night in a similar fashion in both groups. Near-normalization of glucose for 24 h in IDDM did not affect the nocturnal increases in NEFA, GH and lipolysis. In conclusion, a circadian rhythm in lipolysis was found. Increased lipolytic rates during evening-night may at least in part raise nocturnal circulating NEFA. Nocturnal NEFA and lipolysis are further enhanced in IDDM, maybe due to elevated GH, but not to insulinopenia or hyperglycaemia.
 ...
PMID:A circadian rhythm in lipid mobilization which is altered in IDDM. 930 Feb 44

The adipose tissue lipolytic response to spontaneous, non-experimental hypoglycaemic episodes was investigated in patients with IDDM during ordinary life conditions. The absolute concentration of glucose and glycerol in subcutaneous adipose tissue was monitored in mobile patients with microdialysis in 16 IDDM subjects. The absolute glycerol level in adipose tissue was about five times as high as in venous plasma, whereas the glucose concentration was almost the same in the two compartments. Fourteen hypoglycaemic episodes (glucose < 3.5 mmol/l) were recorded. Adipose tissue glycerol increased markedly by 75 % in response to hypoglycaemia and remained increased during at least 4 hours following glucose nadir (F = 3.70, p = 0.003). The circulating levels of free fatty acids increased about three-fold in parallel to the in situ lipolytic response (F = 2.98, p = 0.025). The same lipolytic response was observed whether or not the hypoglycaemic event was perceived by the patient. A rapid decrease in glucose concentration above hypoglycaemic levels did not affect the adipose tissue dialysate glycerol. It is concluded that spontaneous hypoglycaemia elicits a long-term lipolytic response in adipose tissue as evidenced by increased levels of glycerol in adipose tissue with a parallel increase in serum free fatty acids. However, lipolysis is not activated by a rapid glucose decrease per se. The microdialysis method can be used to characterise the lipolytic response to hypoglycaemic episodes in every day life of IDDM patients.
 ...
PMID:Lipolytic response during spontaneous hypoglycaemia in insulin-dependent diabetic subjects. 980 29

To explore further the effects of the human amylin analog pramlintide on overall glycemic control and postprandial responses of circulating glucose, glucagon, and metabolic intermediates in type 1 diabetes mellitus, 14 male type 1 diabetic patients were examined in a double-blind, placebo-controlled, crossover study. Pramlintide (30 microg four times daily) or placebo were administered for 4 weeks, after which a daytime blood profile (8:30 AM to 4:30 PM) was performed. Serum fructosamine was decreased after pramlintide (314+/-14 micromol/L) compared with placebo (350+/-14 micromol/L, P = .008). On the profile day, the mean plasma glucose (8.3+/-0.7 v 10.2+/-0.8 mmol/L, P = .04) and postprandial concentrations (incremental areas under the curve [AUCs] from 0 to 120 minutes) were significantly decreased during pramlintide administration (P < .01 for both) despite comparable circulating insulin levels (359+/-41 v 340+/-35 pmol/L). Mean blood glycerol values were reduced (0.029+/-0.004 v 0.040+/-0.004 mmol/L, P = .01) and blood alanine levels were elevated (0.274+/-0.012 v 0.246+/-0.008 mmol/L, P = .03) after pramlintide versus placebo. Blood lactate concentrations did not differ during the two regimens. During pramlintide administration, the AUC (0 to 120 minutes) for plasma glucagon after breakfast was diminished (P = .02), and a similar trend was observed following lunch. In addition, peak plasma glucagon concentrations 60 minutes after breakfast (45.8+/-7.3 v 72.4+/-8.0 ng/L, P = .005) and lunch (47.6+/-9.0 v 60.9+/-8.2 ng/L, P = .02) were both decreased following pramlintide. These data indicate that pramlintide (30 microg four times daily) is capable of improving metabolic control in type 1 diabetics. This may relate, in part, to suppression of glucagon concentrations. Longer-term studies are required to ascertain whether these findings are sustained over time.
 ...
PMID:The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus. 1042 Dec 39


<< Previous 1 2 3 4 Next >>