Impaired glucose metabolism in hypertensive patients

We have studied glucose tolerance under carefully controlled conditions in 79 patients with arterial hypertension. The results show that, in patients with arterial hypertension but without clinical diabetes mellitus, the glucose tolerance was abnormal in 77.3% and normal in 22.3%. The corresponding figure in the control group of normotensive subjects was 0%. In each test the responses to glucose administration were analyzed by plotting the logarithm of the blood glucose concentration against time. For the points between 60 and 120 min, corresponding to the periods following glucose administration, a linear relationship was obtained and showed a decline at an exponential rate, as noted by other observers. An estimate of the volume of distribution of glucose was obtained as follows. Values observed in hypertensives with a pathological percent fall in blood glucose per minute (Kg) were 29.8 +/- 12.0 (mean +/- SD) liters and those in normal subjects with normal Kg values had a mean of 14.35 +/- 2.98, the difference being highly significant (p less than 0.0001). The results of the theoretical glucose concentration are also presented. Those obtained from subjects with normal Kg values (359.0 +/- 58.4 mg/dl) are significantly higher than in subjects with pathological Kg values (257.6 +/- 51.3 mg/dl; p less than 0.0001). All patients with either pathological or normal Kg values had normal glucose concentration levels, fasting blood sugar and no glucose in the urine specimen. The difference between pathological Kg values (107.0 +/- 25.8 mg/dl) and normal Kg values (90.6 +/- 13.0 mg/dl) was not found to be statistically different (p greater than 0.05). The distribution and means of glucose half time in controls with normal Kg values and hypertensives with pathological Kg values were: 63.5 +/- 11.5 and 137.8 +/- 48.1 min, respectively. The difference between normal and pathological Kg values being statistically significant at a confidence level above 99.5%. We also studied the free glucose pool at zero time. A significantly higher level was found in hypertensives with pathological Kg values, again indicating an impairment in glucose metabolism in this group: 90.6 +/- 26.5 vs. 65.0 +/- 5.4 g (p less than 0.0001). Another study showed an estimate of the mean cellular glucose uptake (MCUg) per minute and per kilogram body weight. The MCUg following glucose loading decreased considerably in hypertensives with pathological Kg values. The percentage reduction ranged between 50 and 55% hypertensives with pathological Kg values 4.1 +/- 0.8, and normotensives with normal Kg values, 8.0 +/- 0.6 (p less than 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)     

White matter abnormalities correlating with memory and depression in heroin users under methadone maintenance treatment

Methadone maintenance treatment (MMT) has elevated rates of co-morbid memory deficit and depression that are associated with higher relapse rates for substance abuse. White matter (WM) disruption in MMT patients have been reported but their impact on these co-morbidities is unknown. This study aimed to investigate changes in WM integrity of MMT subjects using diffusion tensor image (DTI), and their relationship with history of heroin and methadone use in treated opiate-dependent individuals. The association between WM integrity changes from direct group comparisons and the severity of memory deficit and depression was also investigated. Differences in WM integrity between 35 MMT patients and 23 healthy controls were evaluated using DTI with tract-based spatial statistical analysis. Differences in DTI indices correlated with diminished memory function, Beck Depression Inventory, duration of heroin use and MMT, and dose of heroin and methadone administration. Changes in WM integrity were found in several WM regions, including the temporal and frontal lobes, pons, cerebellum, and cingulum bundles. The duration of MMT was associated with declining DTI indices in the superior longitudinal fasciculus and para-hippocampus. MMT patients had more memory and emotional deficits than healthy subjects. Worse scores in both depression and memory functions were associated with altered WM integrity in the superior longitudinal fasciculus, para-hippocampus, and middle cerebellar peduncle in MMT. Patients on MMT also had significant WM differences in the reward circuit and in depression- and memory-associated regions. Correlations among decreased DTI indices, disease severity, and accumulation effects of methadone suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities in MMT.     

Impaired muscle glucose metabolism in acute renal failure

Renal failure is associated with peripheral insulin resistance and consequent carbohydrate intolerance. This report investigates carbohydrate metabolism in vitro in epitrochlearis and hemidiaphragm muscles taken from acutely uraemic and sham-operated rats. Muscles from acutely uraemic rats (compared to those from sham-operated rats ) incubated with 5 mM glucose showed increased rates of basal and insulin-stimulated glycolysis and glycogen turnover, but pyruvate dehydro-genase and tricarboxylic acid - cycle flux was not increased in uraemia. Glycolysis (but not glycogen turnover) in muscles from acutely uraemic rats tended to show decreased responsiveness to stimulation by insulin. It is concluded that acute uraemia is associ-ated with a defect(s) in muscle that produces intrinsic insulin resistance and results in diversion of glucose (both in basal and insulin-stimulated states) from glycogen synthesis into glycolysis.     

Decreased serum testosterone concentration in male heroin and methadone addicts

The serum concentrations of testosterone, estradiol-17β, FSH and LH were measured in 22 male subjects addicted to heroin or methadone. Serum testosterone concentration was decreased in many of these subjects without consistent abnormalities in the other hormones. It is suggested that decreased sexual function in male addicts may be partially due to a decrease in serum testosterone concentration.     

Impaired ability of glycated insulin to regulate plasma glucose and stimulate glucose transport and metabolism in mouse abdominal muscle

Previous studies have shown that glycated insulin is secreted from pancreatic beta-cells under conditions of hyperglycaemia. This study has investigated the effects of monoglycated insulin on plasma glucose homeostasis and in vitro cellular glucose transport and metabolism by isolated abdominal muscle of mice. Monoglycated insulin was prepared under hyperglycaemic reducing conditions, purified by RP-HPLC and identified by electrospray ionisation mass spectrometry (5971.1 Da). When administered to mice at an intraperitoneal dose of 7 nmoles/kg body weight, insulin (non-glycated) decreased plasma glucose concentrations and substantially reduced the glycaemic excursion induced by conjoint intraperitoneal injection of 2 g glucose/kg body weight. In comparison, the same dose of monoglycated insulin decreased plasma glucose concentrations to a lesser extent (P < 0.05), corresponding to an approx. 20% reduction of glucose lowering potency. Using isolated abdominal muscle, insulin (10(-9)-10(-7) M) stimulated dose-dependent increases in cellular 2-deoxy-D-[1-3H]glucose uptake, D-[U-14C]glucose oxidation and glycogen production. Monoglycated insulin was approx. 20% less effective than native insulin in stimulating glucose uptake and both indices of metabolism, generally requiring 10-fold greater concentrations to achieve significant stimulatory effects. These data indicate that the impaired biological activity of glycated insulin may contribute to glucose intolerance of diabetes.     

Impaired inhibitory control in recreational cocaine users

Chronic use of cocaine is associated with impairment in response inhibition but it is an open question whether and to which degree findings from chronic users generalize to the upcoming type of recreational users. This study compared the ability to inhibit and execute behavioral responses in adult recreational users and in a cocaine-free-matched sample controlled for age, race, gender distribution, level of intelligence, and alcohol consumption. Response inhibition and response execution were measured by a stop-signal paradigm. Results show that users and non users are comparable in terms of response execution but users need significantly more time to inhibit responses to stop-signals than non users. Interestingly, the magnitude of the inhibitory deficit was positively correlated with the individuals lifetime cocaine exposure suggesting that the magnitude of the impairment is proportional to the degree of cocaine consumed.     

Medical facilities used by heroin users.

There is little information about the extent of contact between heroin users and medical facilities. In this study of heroin users from general practice we found an increase in the attendance of patients after the onset of heroin use and that a high proportion of appointments were made at general practices compared with hospital departments.     

Impaired glucose tolerance (IGT) is not associated with disturbed homocysteine metabolism

Summary. Elevated plasma total homocysteine (tHcy) has been suggested to be an additional risk factor for cardiovascular disease in subjects with impaired glucose tolerance (IGT) and Type 2 diabetes (T2D). In order to investigate whether an insulin resistant/chronic hyperinsulinemic situation in male diabetic and prediabetic subjects directly influences the tHcy metabolism, fasting tHcy and post-methionine load tHcy plasma levels (PML-tHcy) were determined in 15 men with IGT, 13 men with newly dia-gnosed T2D, and 16 normoglycemic controls (NGT). Fasting tHcy (IGT, 13.1 ± 4.6; T2D, 12.8 ± 4.0; NGT, 10.7 ± 4.4 μmol/L) and PML-tHcy (IGT, 46.5 ± 17.39; T2D, 41.1 ± 6.8; NGT, 38.0 ± 9.7 μmol/L) showed no differences between the groups. Fasting tHcy and PML-tHcy correlated with fasting proinsulin (r = 0.395, p < 0.05; r = 0.386, p< 0.05) and creatinine (r = 0.489, p < 0.01; r = 0.339, p < 0.05), resp. Multiple regression analysis showed only a relationship between fasting tHcy and creatinine. No relationships have been found between fasting tHcy and PML-tHcy, resp., and indicators of an insulin resistant state, e.g., insulin and proinsulin, as well as serum cobalamin and folate concentrations. In conclusion, our data suggest that the degree of glucose intolerance has no direct impact on the metabolism of homocysteine. However, tHcy levels tend to be elevated with the development of nephropathy, indicating an association between tHcy and renal function in these subjects. Received May 11, 1999     

Adipocyte-derived hormones in heroin addicts: the influence of methadone maintenance treatment

Heroin addiction markedly affects the nutritional and metabolic status and frequently leads to malnutrition. The aim of our study was to compare circulating concentration of adipose tissue-derived hormones leptin, adiponectin and resistin in 12 patients with heroin addiction before and after one-year methadone maintenance treatment with the group of 20 age- and body mass index-matched healthy subjects. Basal serum leptin and adiponectin levels in heroin addicts were significantly decreased (3.4+/-0.4 vs. 4.5+/-0.6 ng/ml and 18.9+/-3.3 vs. 33.9+/-3.1 ng/microl, respectively; p 0.05) while serum resistin concentrations were increased compared to healthy subjects (10.1+/-1.2 vs. 4.6+/-0.3 ng/ml; p 0.05). Moreover, positive correlation of serum leptin levels with body mass index was lost in the addicts in contrast to control group. One year of methadone maintenance treatment normalized serum leptin, but not serum adiponectin and resistin concentrations. In conclusion, circulating concentrations of leptin, adiponectin and resistin are markedly altered in patients with chronic heroin addiction. These alterations appear to be relatively independent of nutritional status and insulin sensitivity.     

Self-administration of heroin, acetylmethadol, morphine, and methadone in rhesus monkeys.

Heroin, α-$\text{l}$-acetylmethadol (LAAM), morphine, and methadone each maintained self-administration in rhesus monkeys. The order of relative potency was heroin ≥ LAAM > morphine ≥ methadone. Total daily drug intake increased as dose per injection increased; maximum daily intake was inversely related to relative potency. At high doses, self-injection of methadone and LAAM caused stupor and/or respiratory failure in some monkeys. These toxic effects were partly or completely reversible by naloxone.     

Reversal of morphine, methadone and heroin induced effects in mice by naloxone methiodide

Opioid overdose, which is commonly associated with opioid induced respiratory depression, is a problem with both therapeutic and illicit opioid use. While the central mechanisms involved in the effects of opioids are well described, it has also been suggested that a peripheral component may contribute to the effects observed. This study aimed to further characterise the effects of the peripherally acting naloxone methiodide on the respiratory, analgesic and withdrawal effects produced by various opioid agonists. A comparison of the respiratory and analgesic effects of morphine, methadone and heroin in male Swiss-Albino mice was conducted and respiratory depressive ED(80) doses of each opioid determined. These doses (morphine 9 mg/kg i.p., methadone 7 mg/kg i.p., and heroin 17 mg/kg i.p.) were then used to show that both naloxone (3 mg/kg i.p.) and naloxone methiodide (30-100 mg/kg i.p.) could reverse the respiratory and analgesic effects of these opioid agonists, but only naloxone precipitated withdrawal. Further investigation in female C57BL/6J mice using barometric plethysmography found that both opioid antagonists could reverse methadone induced decreases in respiratory rate and increases in tidal volume. Its effects do not appear to be strain or sex dependent. It was concluded that naloxone methiodide can reverse the respiratory and analgesic actions of a variety of opioid agonists, without inducing opioid withdrawal.