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Endothelin and atrial natriuretic peptide in non-insulin-dependent diabetic versus nondiabetic patients on chronic hemodialysis.

Plasma levels of endothelin (ET) and atrial natriuretic peptide (ANP) are known to be elevated in patients on chronic hemodialysis. Since ET and ANP plasma levels are found to be raised in nonuremic diabetic versus nondiabetic subjects, we wanted to detect a possible difference in plasma levels of these hormones in diabetic versus nondiabetic patients who were on chronic renal replacement therapy. ET is a possible marker of increased vascular atherogenic activity. We measured plasma levels of ET and ANP pre- and posthemodialysis in 23 non-insulin-dependent (NIDDM) diabetic versus 23 nondiabetic patients who were matched according to age and time of day of hemodialysis, and who did not show clinical signs of overt cardiac decompensation. Mean plasma levels of ET and ANP did not differ in diabetic from nondiabetic patients, neither pre- nor postdialysis. In both patient groups, mean ET levels were twice the upper normal limit, did not change significantly pre- versus postdialysis, and did not correlate with blood pressure or with volume ultrafiltration during dialysis. Calcium channel blocker therapy was accompanied by a significant rise of ET pre- and postdialysis in nondiabetic patients but not in diabetic patients. In diabetic patients, ET plasma levels correlated positively with fructosamine levels as an indicator of short-term blood glucose control. Mean ANP plasma levels were about three times the upper normal limit and decreased significantly during dialysis, but this decrease correlated neither with volume ultrafiltration nor with blood pressure. In conclusion, we could not find a difference in plasma levels of ET and ANP for diabetic versus nondiabetic dialysis patients, but impaired short-term blood glucose control in diabetic and calcium channel blocker therapy in only nondiabetic dialysis patients showed concomitant increases in plasma ET levels and thus possibly different mechanisms of ET regulating pathways.

Aged↗

Delay in diagnosis of diabetes mellitus due to inaccurate use of hemoglobin A1C levels.

Testing of hemoglobin A(1C) (HbA(1C)) levels has become widespread in the management of patients with diabetes mellitus. Since the 1980s, it has proven to be an invaluable tool correlating with a patient's average blood glucose levels as well as with their disease morbidity. Clinicians often base treatment decisions and make adjustments depending on a patient's HbA(1C) level. As useful as the HbA(1C) is, it does have notable limitations. A number of conditions can lead to a falsely elevated or a falsely low HbA(1C) level. When one of these conditions is present, it is important to recognize the inaccuracy of the HbA(1C) test to prevent a delay or error in the diagnosis or care of patients with diabetes mellitus. It is also important to be aware of alternative methods of monitoring a patient's diabetes such as a fructosamine assay or home and office blood glucose measurements. Presented is the case of a patient with diabetes mellitus and hereditary spherocytosis, a condition that interfered with her HbA(1C) value and resulted in a delay in her care.

Adult↗

Maitake (Grifola frondosa) improve glucose tolerance of experimental diabetic rats.

We have previously reported that rats with diabetes induced by injecting streptozotocin into neonates showed remarkably lower blood glucose, urine volume, and glucosuria after administration of Maitake (Grifola frondosa). In the present study, we investigated the effects of Maitake on insulin concentration, organ weight, serum composition, and islets of Langerhans in streptozotocin-induced diabetic rats using the same method. The diabetic rats were produced by injecting 80 mg/kg B.W. streptozotocin into 2-d-old neonates. From the age of 9 wk, the rats were given experimental diets for 100 d. The diabetes and control groups were given either diets containing 20% Maitake (DM and CM groups) or control diets (D and C groups). During administration of the experimental diets, we measured body weight, food intake, amount of feces, and serum insulin concentration at glucose loading. The glucose tolerance test was performed at the 10th week after the start of the experimental diets. The D group had an initial fasting blood glucose of 225+/-49 mg/dL, and a maximum blood glucose of 419+/-55 mg/dL at 60 min. In the DM group, however, the initial fasting blood glucose was 170+/-23 mg/dL, and the maximum blood glucose was 250+/-41 mg/dL at 15 min. Both values were markedly lower than those in the D group (p<0.05). The insulin concentration at 15 min. after glucose loading in the DM group was 41+/-16 microU/mL, which was significantly higher than that in the D group (15+/-7 microU/mL) (p<0.05). After the 100-d experimental period, blood samples were collected. The fructosamine level was significantly lower in the DM group (152+/-21 mmol/L) than in the D group (185+/-13 mmol/L). The concentration of 1.5-A.G. (1.5-anhydro glucitol) was significantly higher in the DM group (9.33+/-2.42 microg/mL) than in the D group (1.33+/-0.52 microg/mL). Observation of insulin antibody stain in the Langerhans cells of the pancreas using ABC method showed a decrease insulin antibody stain in the D group. The cells of the DM group were stained more darkly than those of the D group. From these results, we postulated that the bioactive substances present in Maitake can ameliorate the symptoms of diabetes.

Animals↗

Serum pentosidine as an indicator of Alzheimer's disease.

Pentosidine, an advanced glycation end product (AGE), was assayed by HPLC in serum proteins from patients with Alzheimer type dementia (AD), patients with diabetes mellitus (D), and healthy (C) age-matched old subjects (mean age from each group = 84 years). Serum pentosidine was significantly different between the three groups despite similar renal function (serum creatinine < 160 micromol/L). In all groups of patients, pentosidine was independent of glycated hemoglobin (HbA1C) and the early glycation marker fructosamine and appeared to be an independent marker, mainly bound to serum albumin. Pentosidine could be an important factor useful for the diagnosis of Alzheimer's disease.

Aged↗

Insulin secretion and sensitivity during oral glucose tolerance test in Korean lean elderly women.

Impaired glucose tolerance (IGT) and type 2 diabetes including undiagnosed isolated postchallenge hyperglycemia (IPH) are common in the elderly. The aim of this study was to investigate the insulin secretion and sensitivity in Korean elderly lean diabetic women. Forty-one lean women aged 65-88 years took 2 hr oral glucose tolerance test (OGTT) and were stratified according to the WHO criteria (normal glucose tolerance [NGT], n=20; IGT, n=6; and type 2 diabetics, n=15 including seven IPH). HbA1c and fructosamine progressively increased from the NGT to the diabetic subjects (p=0.006 and p=0.001, respectively). Compared with subjects with NGT, the insulinogenic index, a marker of early insulin secretion and the AUC(ins), a marker of total insulin secretion, decreased significantly in diabetic group [0.53 (-0.44 -1.45) vs. 0.18 (0.00 -1.11), p=0.03 and 306+/-165 vs. 199+/-78 pmol/L, p=0.02 respectively]. A significant difference was found in the AUC(c-peptide) among each group (221+/-59 vs. 206+/-34 vs. 149+/-51 pmol/L, p=0.001 for each). The homeostasis model assessment of insulin resistance (HOMA-IR), a marker of insulin resistance, was not different among the groups. We conclude that compared with NGT subjects, elderly lean women with diabetes have impaired oral glucose-induced insulin secretion but have relatively preserved insulin sensitivity. This suggests that insulin resistance is not necessarily an essential component of Korean elderly lean diabetic women.

Aged↗

Rooibos tea (Aspalathus linearis) partially prevents oxidative stress in streptozotocin-induced diabetic rats.

The aim of this study was to investigate the effects of rooibos tea as a natural source of a wide scale of antioxidants on the prevention and treatment of oxidative stress in streptozotocin-induced diabetic rats. Expected significant changes of biochemical parameters characteristic for experimental diabetic state were found in plasma and tissues eight weeks after single dose streptozotocin application. Administration of aqueous and alkaline extracts of rooibos tea (or N-acetyl-L-cysteine for comparison) to diabetic rats did not affect markers of the diabetic status (glucose, glycated hemoglobin and fructosamine). Besides the parameters characterizing hepatotoxic effect of streptozotocin, rooibos tea significantly lowered advanced glycation end-products (AGEs) and malondialdehyde (MDA) in the plasma and in different tissues of diabetic rats, particularly MDA concentration in the lens. From these results we can conclude that antioxidant compounds in rooibos tea partially prevent oxidative stress and they are effective in both hydrophobic and hydrophilic biological systems. Therefore, rooibos tea as a commonly used beverage can be recommended as an excellent adjuvant support for the prevention and therapy of diabetic vascular complications, particularly for protecting ocular membrane systems against their peroxidation by reactive oxygen species.

Acetylcysteine↗

Comparison between surgeons and general practitioners with respect to cardiovascular and psychosocial risk factors among physicians.

The incidence of mortality from ischemic heart disease in Sweden has been reported to be elevated for surgeons in comparisons with most other groups of physicians. The objective of the present investigation was to compare cardiovascular risk factors and psychosocial work characteristics of surgeons and general practitioners, the latter having a substantially lower rate of ischemic heart disease. A random sample of 36 male surgeons and 30 male general practitioners was selected. The results showed no clear-cut differences in physiological risk factors. Overall mental strain was greater among the surgeons, as was the inability to relax after work, perceived work tempo, and total number of workhours. There were significant associations between psychosocial work characteristics and traditional cardiovascular risk factors, and the study gives further support to the validity of using long-term glucose markers, such as fructosamine, as indicators of metabolic stress.

Coronary Disease↗

An experimental study on the effects of polymorphiasis in common eider ducklings.

Eight common eider (Somateria mollissima) ducklings were experimentally infected from 1 June through 13 June, 1995 with acanthocephalans (Polymorphus minutus) by allowing the birds to feed on Gammarus spp. (Gammarus oceanicus, G. salinus, G. zaddachi, and G. lacustris) containing acanthocephalan cystacanths. Uninfected Gammarus spp. were fed to a control group of seven ducklings. No mortality of ducklings occurred during the experiment. However, the infected ducklings gained weight more slowly than the control birds. After the 2 wk study period, the mean serum concentrations of total protein, albumin, beta-globulin, gamma-globulin, fructosamine and creatine kinase were lower in the infected group than in the controls. The mean (+/-SE) number of acanthocephalans in the intestine of the infected ducklings was 21 (+/-4). The parasites were attached to the mucosa of the posterior small intestine of the infected ducklings with a mixed inflammatory reaction consisting of heterophils and mononuclear lymphocytes surrounding the attachment sites.

Acanthocephala↗

[Magnesium supplementation to patients with type II diabetes].

The purpose of this study was to evaluate Mg status by nuclear magnetic resonance spectroscopy in a group of well-regulated non-insulin-dependent diabetic (NIDDM) patients without angiopathy. Furthermore, to investigate the effect of Mg supplementation on markers of diabetic control, hemostatic function, platelet reactivity and endothelial function in the same patient population. A double-blinded, placebo-controlled and randomized crossover study was carried out, with two 8-weeks treatment periods (360 mg Mg/day) separated by a 4-weeks wash-out period. 11 well-regulated NIDDM patients participated in the study. Eight weeks of Mg supplementation significantly raised the level of free intracellular Mg in the diabetic patients (157.35 +/- 16.53 vs. 197.49 +/- 27.60 microM; p < 0.01). No changes were observed neither in plasma level of von Willebrand factor antigen, fibrinogen and fibronectin nor in platelet release of thromboxane B2 (TxB2). Similarly, markers of diabetic regulation, HbA1c and fructosamine, showed no significant changes. These results suggest that even well regulated NIDDM patients have marked Mg deficiency. Restoring this deficiency had no effect on diabetic control, markers of platelet reactivity, hemostatic function and endothelial function.

Adult↗

A new generation of oral hypoglycemics. Their use, measurement, and effects on insurance risk assessment.

The increased use of oral hypoglycemics among the more than 14 million diabetics in the United States and the development of new pharmaceutical formulations requires the continued surveillance of their use in the insurance applicant population. Routine monitoring of urine glucose or even blood glucose or fructosamine measurements often fail to detect the diabetic using oral hypoglycemics. Urine analysis for the use of first generation sulfonylureas has shown a declining prevalence of their use due to the increased number of prescriptions written for newer and more effective drugs. In order to monitor the use of these second-generation oral hypoglycemics, an immunoassay was developed to detect the use of glyburide, 1-[4-[2-(5 chloro-2-methoxybenzamido) ethyl]-phenyl] sulfonyl]-3-cyclohexylurea. After testing in a defined population of known users of this class of sulfonylureas, the assay was applied to a random population of 12,000 applicants applying for life insurance. Results demonstrate the predictive value of this assay in determining the prevalence of use of this drug in the insurance-buying population and its assistance in risk assessment.

Diabetes Mellitus↗

[The effect of streptozotocin-induced diabetes in the neonatal period on hepatic mitochondrial bioenergetics in adult rats].

BACKGROUND: Previous experimental studies focused on the liver mitochondrial bioenergetic changes in diabetes mellitus type I induced in adult animals. Information about the effects of persisting neonataly induced diabetes mellitus type I on the mitochondrial bioenergetics are missing. AIM: The aim of the study was to assess the degree of diabetes mellitus compensation and parameters of oxidative phosphorylation in rats aged 3 months with DM persisting from neonatal period. METHODS: DM was induced in male Wistar rats by repeated intraperitoneal administration of streptozotocine 45 mg/kg on 2nd and 9th day after birth. The concentrations of glucose, glycosylated haemoglobin, fructosamine were detected in the blood and the concentration of cholesterol and triacylglycerols in the blood and liver tissue, respectively. After mitochondria isolation from the liver we measured parameters of oxidative phosphorylation by polarography using Clark oxygen electrode. RESULTS: In the group of neonataly induced DM the concentration of glucose (23.10 +/- 1.55 vs 8.3 +/- 0.56 mmol/l), glycosylated haemoglobin (6.04 +/- 1.17 vs 3.99 +/- 0.44%) and blood cholesterol concentration (2.15 +/- 0.11 vs 1.83 +/- 0.09 mmol/l) increased significantly (p < 0.001 and p < 0.005 for cholesterol) comparing to a group of healthy rats. No statistically significant differences were found in the remaining parameters when comparing these two groups. The parameters of oxidative phosphorylation were significantly (p < 0.001) decreased in the group with DM comparing to control group of healthy animals--the index of respiratory control (4.87 +/- 0.25 vs 9.57 +/- 0.34), the rate of oxygen consumption in the stage 3 in ADP presence (88.61 +/- 4.62 vs 165.08 +/- 4.5 natO.mg/protein/min) and phosphorylation rate (203.54 +/- 7.26 vs 332.87 +/- 7.39 nmolATP.mg/protein/min) with NAD substrate glutamate. Similar trend was also seen with FAD substrate succinate. The index of oxidative phosphorylation ADP:0 was not changed in both groups. CONCLUSIONS: In 3 months old rats with neonataly induced DM the development of steatosis was not observed and uncoupling of oxidative processes from phosphorylation did not appear. Energy production was sufficient enough for normal functions of the liver and to ensure all needs of the organism. (Tab. 4, Ref. 51.)

Aging↗

[Factors affecting birthweight in insulin-dependent diabetes mellitus pregnancy].

Fetal growth is affected by various maternal factors. Metabolic disturbances often present in pregnancy complicated by insulin-dependent diabetes mellitus may have important effect on birthweight. The aim of this study was to evaluate the influence of maternal morphometric and metabolic factors on birthweight parameters in women with IDDM. Data were analyzed from 124 diabetic women who delivered in I Department of Obstetrics and Gynaecology University Medical School in Warsaw between 1989-1998. Maternal morphometric factors, glycemic control, insulin requirement, glycosylated hemoglobin and fructosamine levels were correlated with birthweight and birthweight ratios. Glycemic control in first weeks of second part of pregnancy as well as maternal height and weight gain during pregnancy affected birthweight in women with insulin-dependent diabetes mellitus.

Adult↗

[Prevalence of diabetes mellitus in the adult German population].

In the German National Health Interview and Examination Survey 7,124 subjects of a representative sample of the 18 to 79 year old population having their residence in Germany were interviewed and medically examined. Using a self-administered questionnaire as well as a subsequent personal interview by a physician, the participants were questioned regarding past and present diseases. Based on the data of the physicians' interviews, the prevalence rate for diabetes was 4.7% for men and 5.6% for women in the examined age-group. There is a strong increase of the prevalence with age. According to the present data nearly every fifth women in the age range from 70 to 79 years is suffering from diabetes mellitus. The disease is much more frequent in the new federal states (former GDR) than in the old ones (former West Germany). About one fourth of the diabetics uses insulin, far more than 40% are on oral antidiabetics. According to the interrogation of the physicians, about half of the diabetics not using any drugs are not even on a diet (ca. 15%). The portion of undetected diabetics in the examined population is estimated to be about 1% considering the values of blood and urine parameters (glucose in serum and urine, fructosamine, HbA1c).

Adolescent↗

Changes of acute-phase proteins in streptozotocin-induced diabetic rats.

Quantitative and qualitative changes of serum proteins, apart from glycation, have not been sufficiently studied in streptozotocin-induced diabetic rats (D), the most common experimental model for diabetes. Thus, we decided to analyze the serum of diabetic rats by concanavalin A-blotting in comparison with rats with acute inflammation induced by fermented yeast (Y), in which characteristic alterations of serum proteins have been described. Two months after the streptozotocin treatment, the blood glucose levels were highly elevated (456+/-24 vs. 124+/-10 mg/dl, p<0.001, n=12), the body weight was significantly lower than normal (279+/-10 vs. 392+/-6 g, p<0.001, n=12), and serum proteins appeared to be highly glycated (p<0.001) when analyzed by the fructosamine assay, without any significant change in the total serum protein concentration. Analysis by concanavalin A-blotting, revealed a significant decrease of alpha1-inhibitor-3 (alpha1-I3, p<0.05) and an increase of the beta chain of haptoglobin (beta-Hp, p<0.05) in both D and Y rats (n=3) compared with control animals. However, acute inflammation caused a marked rise of two prominent acute phase proteins, alpha2-macroglobulin and hemopexin, which did not change appreciably in diabetic rats. Further work will be necessary to evaluate the physiopathological significance of these phenomena which could result from changes of both concentration and glycosylation of the aforementioned proteins.

Acute-Phase Proteins↗

[Clinical significance of serum LpA-I levels measured by immunoturbidimetric assay in type 2 diabetes mellitus patients].

Previously, we developed an immunoturbidimetric assay method for lipoprotein A-I(LpA-I) on sera pre-absorbed with anti-apolipoprotein A-II. In the present study, correlations between serum lipoprotein A-I and other serum parameters levels were examined and LpA-I levels were studied in patients with type 2 diabetes mellitus. The serum levels of LpA-I did not correlate with those of diabetic markers such as fasted blood glucose, glycohemoglobin(HbA1c) and fructosamine, but correlated well with the levels of total cholesterol and HDL cholesterol, phospholipids, apolipoprotein A-I and seemed to correlate inversely with arteriosclerosis index. In patients with type 2 diabetes mellitus, LpA-I levels were significantly lower than those in normal subjects. Especially, LpA-I levels of patients with diabetic complications were significantly lower than those in normal subjects and non-complicated diabetic patients. Then, the measurement of LpA-I levels in patients with type 2 diabetes mellitus was considered to be useful for prevention and management of arteriosclerosis.

Adult↗

Sex hormone-binding globulin in gestational diabetes.

BACKGROUND: Insulin is an important regulator of serum sex hormone-binding globulin (SHBG) concentration which works by inhibiting its production in hepatocytes. Low SHBG level is associated with increased insulin resistance and hyperinsulinemia. Our purpose was to compare maternal serum SHBG level between normal and gestational diabetic pregnant women and to study the relationships between SHBG, SHBG/insulin and SHBG/glucose ratio and several endocrine, metabolic and clinical parameters. METHODS: Serum SHBG concentrations were measured in 34 women with gestational diabetes and in 32 matched controls. Glucose, insulin, C-peptide, fructosamine, beta-HCG, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein A, apolipoprotein B, total and free T4, total and free estriol, T3 and IGF-1 were measured. Insulin sensitivity was estimated using the short insulin tolerance test. RESULTS: SHBG, SHBG/insulinemia ratio and SHBG/glucose ratio were significantly lower in the diabetic group (309.54 +/- 112.22 vs 460.54 +/- 144.54, p = 0.00001), (33.55 +/- 16.62 vs 72.56 +/- 66.50, p = 0.0006 using log-transformed values), (5.88 +/- 1.87 vs 3.39 +/- 1.23, p < 0.00001). SHBG was negatively correlated with insulinemia (r = -0.40, p = 0.001), C-peptide (r = -0.41, p = 0.001), glycemia (r = -0.27, p = 0.02), diastolic blood pressure (r = -0.41, p = 0.001) and beta-HCG (r = -0.41, p = 0.001) and positively correlated with LDL-c (r = 0.25, p = 0.04) and apolipoprotein B (r = 0.33, p = 0.007). CONCLUSIONS: SHBG concentrations are lower in gestational diabetic pregnant women and are related to insulin levels but not to peripheral insulin sensitivity. Since insulinemia was similar in normal and gestational diabetic pregnant women, we speculate that gestational diabetes is characterized by a higher peripheral insulin resistance, a fasting normal insulinemia and a higher hepatic insulin sensitivity, at least in other actions than on carbohydrate metabolism. The role of sex steroids, T4 and IGF-1 in regulating SHBG appears to be limited during pregnancy.

Adult↗

Effects on urinary albumin excretion and renal function changes by delapril and manidipine in normotensive type 2 diabetic patients with microalbuminuria.

This study was designed to investigate the effect of delapril, an ACE inhibitor, and manidipine, a long action calcium antagonist, on persistent microalbuminuria in normotensive type 2 diabetic patients. Sixty type 2 diabetic patients were randomized to take delapril 30 mg/day or manidipine 10 mg/day for 48 weeks, in an open label design. Twenty eight of thirty subjects in the delapril group and twenty nine of thirty in the manidipine group completed the study. Urine albumin excretion as measured by the urinary albumin creatinine ratio decreased significantly in both groups (112.0+/-60.9 to 95.3+/-64.9 mg/g and 108.5+/-51.0 to 96.4+/-53.5 mg/g in the delapril and manidipine group respectively, p < 0.05, by paired t-test). Systolic and diastolic blood pressure were not significantly changed after treatment in the delapril group but significantly decreased in the manidipine group (130.9+/-7.1/80.2+/-6.1 to 127.2+/-7.1/78.0+/-5.3 mm/Hg, p < 0.05, by student's paired t-test). After 48 weeks of treatment, two patients in the delapril group and one patient in the manidipine group converted to normoalbuminuria (urinary albumin:creatinine ratio < 30 mg/g) and one patient in each group progressed to overt nephropathy (urinary albumin:creatinine ratio > 300 mg/g). There were no significant changes in fasting plasma glucose, HbA1c, serum fructosamine, creatinine, potassium and lipid profiles after 48 weeks of treatment in both groups. Two cases in the delapril group were withdrawn during the study because of an intolerable cough and one case in the manidipine group because of intolerable dizziness and headache. In conclusion, both delapril and manidipine are effective in the reduction of microalbuminuria in normotensive type 2 diabetic patients with persistent microalbuminuria.

Adult↗

Oral chromium picolinate and control of glycemia in insulin-treated diabetic dogs.

Chromium is an essential dietary trace mineral involved in carbohydrate and lipid metabolism. Chromium is required for cellular uptake of glucose, and chromium deficiency causes insulin resistance. Chromium supplementation may improve insulin sensitivity and has been used as adjunct treatment of diabetes mellitus in humans. In this study, 13 dogs with naturally acquired diabetes mellitus were treated with insulin for 3 months, then with insulin and chromium picolinate for 3 months. Dogs weighing <15 kg (33 lb: n = 9) were administered 200 microg of chromium picolinate PO once daily for I month, then 200 microg of chromium picolinate twice daily for 2 months. Dogs weighing >15 kg (n = 4) received 200 microg of chromium picolinate once daily for 2 weeks, then 200 microg twice daily for 2 weeks, then 400 microg twice daily for 2 months. Type of insulin, frequency of insulin administration, and diet were kept constant, and insulin dosage was adjusted, as needed, to maintain optimal control of glycemia. Mean body weight, daily insulin dosage, daily caloric intake, 10-hour mean blood glucose concentration, blood glycated hemoglobin concentration, and serum fructosamine concentration were not markedly different when dogs were treated with insulin and chromium picolinate, compared with insulin alone. Adverse effects were not identified with chromium picolinate administration. Results of this study suggest that, at a dosage range of 20-60 microg/kg/d, chromium picolinate caused no beneficial or harmful effects in insulin-treated diabetic dogs.

Administration, Oral↗