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PubMed1990

Effects of alpha-glucosidase inhibition and viscous fibre on diabetic control and postprandial gut hormone responses.

Twelve sulphonylurea-treated Type 2 diabetic patients underwent treatment for 2-week periods with the absorbable alpha-glucosidase inhibitor BAY m1099 (50 mg thrice daily) and with guar granules (5 g thrice daily) separately and together in a sequence-randomized double-blind placebo-controlled study. BAY m1099 and guar reduced the mean fasting plasma glucose from 10.0 +/- 0.7 mmol l-1 to 8.7 +/- 0.5 (p less than 0.05) and 8.3 +/- 0.7 mmol l-1 (p less than 0.01), respectively. Both agents also lowered home-monitored postprandial blood glucose, with BAY m1099 exerting the greater effect. Guar, but not BAY m1099, lowered serum cholesterol from 5.43 +/- 0.52 to 5.29 +/- 0.31 mmol l-1 (p less than 0.05). BAY m1099 reduced the test breakfast plasma responses of glucose (p less than 0.001) and gastric inhibitory polypeptide (GIP, p less than 0.01) and increased those of peptide tyrosine-tyrosine (p less than 0.05) and motilin (p less than 0.01). Guar also reduced plasma glucose concentrations after a test breakfast (p less than 0.05) and increased the response of neurotensin (p less than 0.05). Combining treatments gave no further reduction of postprandial blood glucose concentration and was associated with an increased incidence and severity of gastrointestinal side-effects.

1-Deoxynojirimycin↗
PubMed1991

Predominantly vegetarian diet in patients with incipient and early clinical diabetic nephropathy: effects on albumin excretion rate and nutritional status.

Several studies have suggested that dietary protein quality may be an important determinant in the natural history of renal disease. We have therefore studied the effects of a predominantly vegetarian diet in eight patients with Type 1 diabetes mellitus and an albumin excretion rate (AER) in excess of 30 micrograms min-1. The AER was measured after an 8-week run-in period on the patient's usual diet, and again after 8 weeks of a predominantly vegetarian diet in which the proportion of vegetable protein was supplemented in order to minimize the reduction in total dietary protein intake. The median fractional albumin clearance fell during the study from an initial value of 188 x 10(-+) (range 58-810 x 10(-4)) at the end of the run-in period to 87 x 10(-4) (23-829 x 10(-4)) at the end of the period on low animal protein diet (difference 79 x 10(-4) (95% Cl 9-149 x 10(-4)), p less than 0.05). The AER then returned to values similar to those obtained at the beginning of the study after a further 8 weeks in those patients returning to their usual diet. No significant changes in blood glucose control or in arterial pressure were observed. A predominantly vegetarian diet may therefore have important beneficial effects on diabetic nephropathy without the need for a heavily restricted total protein intake.

Albuminuria↗
PubMed1991

A six-year follow-up of the relationship between N-acetyl-beta-glucosaminidase and albuminuria in relation to retinopathy.

Fifty patients with Type 1 diabetes mellitus were observed over 6 years. Serum and urinary N-acetyl-beta-glucosaminidase (NAG) activity, and albuminuria were measured in groups of patients subdivided according to ophthalmological findings. Significantly higher mean serum NAG activity was found at the beginning of the study in patients who later developed diabetic retinopathy in comparison with those who did not (geometric mean (2SD range) 19.7 (12.4-31.2) vs 14.4 (9.5-22.7) U l-1, p less than 0.01). Urinary NAG activity was significantly higher in all groups of diabetic patients than in healthy control subjects (p less than 0.05). A significant increase in albumin:creatinine ratio during the study was found in patients with newly developed diabetic retinopathy compared with patients who did not (at 6 years 1.33 (0.40-4.43) vs 0.75 (0.24-2.31) g mol-1, p less than 0.01). No differences in either biochemical variable were found between hypertensive and normotensive diabetic patients at the end of the study. The results suggest that both serum NAG activity and albuminuria may serve as early functional indicators of diabetic retinopathy.

Acetylglucosaminidase↗
PubMed1993

The size of the pancreas in diabetes mellitus.

To determine whether there was an association between the size of the pancreas and the type of diabetes, ultrasonography of the pancreas was performed on 57 diabetic patients: 14 with Type 1 (insulin-dependent) diabetes, 10 insulin-treated and 33 tablet-treated patients with Type 2 (non-insulin-dependent) diabetes, and 19 non-diabetic subjects. The pancreas of patients with Type 1 diabetes was markedly smaller (p < 0.0001) than the pancreas in non-diabetic subjects. The pancreas of patients with Type 2 diabetes was more moderate in size: larger (p < 0.001) than that of Type 1 diabetic patients but smaller (p < 0.5) than the pancreas of the control group. Pancreatic size of patients with Type 2 diabetes was also related to basal insulin secretion with insulin-deficient patients (low or undetectable C-peptide) having smaller (p < 0.05) pancreases than those with normal insulin secretion. There was no difference in the size of the pancreas in the different treatment groups of Type 2 diabetic patients. Pancreatic size did not correlate with age, body mass index or the duration of diabetes. We conclude that the pancreas is a smaller organ in patients with diabetes mellitus and that the decrement in size is maximal in insulin-dependent/insulin-deficient subjects. Ultrasonography, therefore, can potentially serve to discriminate between the different types of diabetes.

Adolescent↗
PubMedDate not supplied

Is serum anhydroglucitol an alternative to the oral glucose tolerance test for diabetes screening? The Mauritius Noncommunicable Diseases Study Group.

The oral glucose tolerance test is inconvenient for diabetes screening. In clinical studies a reduced serum anhydroglucitol level has proved to be a sensitive and specific test for diabetes. A new minicolumn enzymatic method which is simple and robust makes use in population screening feasible. The aim of our study was to assess the usefulness of a single measurement of anhydroglucitol to screen for diabetes and impaired glucose tolerance. Assays were performed on samples taken from 227 Mauritian Chinese subjects at the time of glucose tolerance testing. Subjects had normal glucose tolerance (n = 82), impaired glucose tolerance (n = 76), newly diagnosed diabetes (n = 38), and known diabetes (n = 31). Anhydroglucitol concentrations (mean +/- SD) were similar for normal and impaired glucose tolerance subjects (23.7 +/- 8.2 vs 23.4 +/- 8.6 mg l-1). Although the differences between normal and newly diagnosed diabetes (15.0 +/- 11.0 mg l-1) and known diabetic subjects (11.8 +/- 10.6 mg l-1) were significant (p < 0.001), diagnostic sensitivity and specificity were poor. We conclude that measurement of serum anhydroglucitol is not suitable for screening for the diagnoses of impaired glucose tolerance and diabetes.

Adult↗
PubMedDate not supplied

Obese patients with type 2 diabetes poorly controlled by insulin and metformin: effects of adjunctive dexfenfluramine therapy on glycaemic control.

Dexfenfluramine is well known for its weight reducing action and has been reported to improve glycaemic control in obese Type 2 diabetic patients not adequately controlled on conventional oral hypoglycaemic therapy. In this double-blind placebo-controlled study, 20 obese Type 2 diabetic patients with mean HbA1c of 8.8 +/- 0.5% (normal range 3.5-6.0%), and mean body mass index (BMI) of 34.4 +/- 1.0 kg m-2, who were poorly controlled on insulin (mean dosage 58.0 +/- 6.1 units day-1) were randomized to receive either additional dexfenfluramine or placebo for 12 weeks. Seventeen of these patients were already taking maximum tolerated metformin therapy (mean dosage 1.6 +/- 0.2 g day-1) and the other three were unable to tolerate any at all. At baseline, the dexfenfluramine and placebo groups were similar in all parameters studied. After the 12-week treatment period, median HbA1c had fallen in dexfenfluramine treated patients from 8.5 (interquartile range (IR): 7.5-10.3) to 7.1% (IR: 6.7-7.5; p < 0.02). The fall in HbA1c in individual patients after treatment with dexfenfluramine was strongly associated with weight loss (r = 0.69; p < 0.04), although as a group the changes in weight and BMI were not statistically significant. Placebo was without effect. These results show that in the obese patient with Type 2 diabetes who is poorly controlled despite large daily doses of insulin and metformin, adjunctive dexfenfluramine can improve glycaemic control without exacerbating weight gain.

Biomarkers↗
PubMed1995

Diabetes care in South Asian and white European patients with type 2 diabetes.

Aspects of diabetes care in South Asian and white European patients with Type 2 diabetes attending a hospital review clinic were explored. Among the clinic population of 1710 patients, 258 (15%) were of South Asian origin. A significantly greater proportion (95% CI for difference in proportions 8-22%) of these patients was treated with oral hypoglycaemic drugs than in white Europeans, in whom there was a correspondingly greater proportion receiving insulin treatment. In a case-control study, where 154 patients in each racial group were stratified according to treatment regimen, significantly more South Asian patients (13/30 vs 6/30, p < 0.05) on insulin were treated with a once-daily regimen. Despite these observed differences in treatment of diabetes, glycaemic control was no worse in South Asian patients when compared to their white European counterparts. South Asian diabetic patients attending hospital diabetes clinics in the UK can experience similar levels of glycaemic control to white Europeans.

Asia↗
PubMed2005

Purification and characterization of a fructosyltransferase from onion bulbs and its key role in the synthesis of fructo-oligosaccharides in vivo.

A fructosyltransferase that transfers the terminal (2 --> 1)-beta-linked D-fructosyl group of fructo-oligosaccharides (1(F)(1-beta-D-fructofuranosyl)(n) sucrose, n >/= 1) to HO-6 of the glucosyl residue and HO-1 of the fructosyl residue of similar saccharides (1(F)(1-beta-D-fructofuranosyl)(m) sucrose, m >/= 0) has been purified from an extract of the bulbs of onion (Allium cepa). Successive column chromatography using DEAE-Sepharose CL-6B, Toyopearl HW65, Toyopearl HW55, DEAE-Sepharose CL-6B (2nd time), Sephadex G-100, Concanavalin A Sepharose, and Toyopearl HW-65 (2nd time) were applied for protein purification. The general properties of the enzyme, were as follows: molecular masses of 66 kDa (gel filtration chromatography), and of 52 kDa and 25 kDa (SDS-PAGE); optimum pH of c. 5.68, stable at 20-40 degrees C for 15 min; stable in a range of pH 5.30-6.31 at 30 degrees C for 30 min, inhibited by Hg(2+), Ag(+), p-chloromercuribenzoic acid (p-CMB) and sodium dodecyl sulfate (SDS), activated by sodium deoxycholate, Triton X-100 and Tween-80. The amino acid sequence of the N-terminus moiety of the 52-kDa polypeptide was ADNEFPWTNDMLAWQRCGFHFRTVRNYMNDPSGPMYYKGWYHLFYQHNKDFAYXG and the amino acid sequence from the N-terminus of the 25-kDa polypeptide was ADVGYXCSTSGGAATRGTLGPFGLL VLANQDLTENTATYFYVSKGTDGALRTHFCQDET. The enzyme tentatively classified as fructan: fructan 6(G)-fructosyltransferase (6G-FFT). The enzyme is proposed to play an important role in the synthesis of inulin and inulinneo-series fructo-oligosaccharides in onion bulbs.

Amino Acid Sequence↗
PubMed1993

Determinants of birth-weight in women with established and gestational diabetes.

Increased birth-weight (macrosomia) can complicate the diabetic pregnancy, but many factors other than hyperglycaemia can influence birth-weight, in particular maternal obesity. In a mixed population (European, Maori and Pacific Islander) with a high prevalence of glucose intolerance and obesity we have examined the relative impact of various maternal factors on birth-weight in women with both established and gestational diabetes. Mean birth-weight was significantly greater in women with established or gestational diabetes than in controls (p < 0.0001), but was similar in women with gestational and established diabetes, despite glycaemic control being significantly poorer (p < 0.0001) in the latter. Birth-weight closely paralleled prepregnancy body mass index rather than glycaemic control, but in Maori women it was lower than expected, probably because of their high prevalence of smoking. Daily cigarette consumption was negatively correlated with birth-weight (p < 0.01) despite the smokers having significantly poorer glycaemic control (p < 0.001). The most significant variables influencing birth-weight in the diabetic pregnancy were gestational age at delivery, prepregnancy body mass index, maternal height, estimated weight gain during pregnancy, the presence of hypertension and cigarette smoking (the latter 2 having negative effects on birth-weight). Glycaemic control in the last half of pregnancy was not significant in this analysis. We conclude that within the limits of glycaemic control which we obtained, birth-weight was largely determined by maternal factors other than hyperglycaemia. Birth-weight thus has severe limitations as an outcome measure of the diabetic pregnancy.

Adult↗
PubMed2001

Effects of 2,2',5,5'-tetrachlorobiphenyl and biphenyl on cell membranes of Ralstonia eutropha H850.

The effects of 2,2',5,5'-tetrachlorobiphenyl (TeCB), a PCB congener, and biphenyl on the cytoplasmic membranes of Ralstonia eutropha H850 were investigated by measuring fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene (DPH) as the probe, and determining the cellular fatty acid compositions. TeCB significantly affected the membrane of R. eutropha H850 cells grown on fructose by decreasing DPH fluorescence polarization. In contrast, the membrane of cells grown on biphenyl showed a considerably less significant effect of TeCB on membrane polarization than in fructose-grown cells. An increase in the ratio of total saturated to unsaturated fatty acids in cells grown on biphenyl suggested less of a fluidizing effect of TeCB on membranes in those cells. When biphenyl-grown cells were transferred back to a fructose medium, they required 25 generations for the membrane polarization and fatty acid compositions of these cells to revert back to those of the initial fructose-grown cells. The re-adaptation to a change in temperature required only five generations to return to normal. These results show that biphenyl affects cells in more ways than simply fluidizing the cytoplasmic membrane.

Adaptation, Biological↗
PubMed1995

Visual field defects in diabetic children without retinopathy. Relation between visual function and microalbuminuria.

The effects of diabetes on retinal function before the onset of clinically detectable retinopathy have been investigated with several methods. Our aim is to evaluate the usefulness of computerized perimetry in early diagnosis of retinal sensitivity impairment in lack of fluorescein angiographic signs of diabetic retinopathy. Seventy diabetic children and adolescents, 39 normoalbuminuric and 31 microalbuminuric patients, and 70 normal subjects were investigated with static computerized perimetry. Normoalbuminuric patients showed functional parameters similar to those of controls, while microalbuminuric patients had a significant reduction of mid-peripheral light sensitivity in comparison with both normoalbuminuric children and controls. Our data suggest that an impaired light sensitivity, in mid-periphery of the visual field, is present in diabetic patients with persistent microalbuminuria.

Adolescent↗
PubMed2005

Naturally occurring menopause in cynomolgus monkeys: changes in hormone, lipid, and carbohydrate measures with hormonal status.

Naturally occurring post-menopausal (PM) female cynomolgus monkeys (Macaca fascicularis) were identified. Their sex hormone profile was characterized and compared with younger pre-menopausal females before and after ovariectomy (OVX). PM females had lower estrogens and increased follicle-stimulating hormone (FSH) concentrations. Two PM females had diabetes mellitus and elevated androgens (androstenodione and dihydroepiandrosterone sulfate). Non-diabetic PM females were given parenteral E(2) which normalized FSH, and caused improvements in body weight, plasma lipids and lipoprotein cholesterol. Androgens remained lower with E(2) treatment. OVX induced comparable increases in FSH seen with the PM monkeys, however they had lower body weights, and had higher estrone and androstenodione concentrations. Natural menopause occurs in cynomolgus monkeys and hormone changes with OVX are similar however, differences in sex hormones that can relate to body mass and age may be important. E(2) treatment restored estrogen levels and induced improvements in the lipid profile of PM females.

Androstenedione↗
PubMed2002

High-fat high-energy feeding impairs fasting glucose and increases fasting insulin levels in the Göttingen minipig: results from a pilot study.

High-fat diet and obesity are known to be of major importance for development of type 2 diabetes in humans. High-fat feeding can induce syndromes of glucose intolerance and/or insulin resistance in several species, and the Göttingen minipig might be a useful model for studying the effect of dietary high-fat intake and obesity on glucose homeostasis and the susceptibility to diabetes. The present study was designed as a pilot study to investigate the effects of obesity caused by high-fat high-energy feeding on oral and intravenous glucose tolerance. Male Göttingen minipigs were fed a control diet (CD) or a high-fat high-energy diet (HFD) for 3 months. Body weight (32.6 +/- 2.4 kg vs. 24.9 +/- 0.5 kg, p < 0.001) and total (13.2 +/- 3.2% vs. 6.1 +/- 0.5%, p = 0.002) and truncal (11.0 +/- 3.9% vs. 1.8 +/- 1.1%, p = 0.001) fat percent were increased significantly, whereas relative lean body mass was decreased (84.8 +/- 3.3% vs. 91.9 +/- 0.5%, p = 0.002) in the HFD group compared to CD. Fasting plasma glucose (4.3 +/- 0.4 mM vs. 3.6 +/- 0.3 mM, p = 0.023) and insulin (80 +/- 23 pM vs. 23 +/- 21 pM, p = 0.012) were increased in the HFD group compared to CD, but oral glucose tolerance was not significantly changed. Insulin responses to intravenous glucose were increased (6741 +/- 2538 vs. 3938 +/- 771 pM 3 min, p = 0.050), while glucose clearance was not changed by HFD vs. CD, thus indicating insulin resistance. In conclusion, changes in body weight and composition, resulting in minor abnormalities in glucose tolerance and insulin sensitivity, characterized by slight hyperglycemia and compensatory hyperinsulinemia, can be induced in the male Göttingen minipig by high-fat high-energy feeding for 3 months. This approach seems to be an interesting and promising method for establishment of a nonrodent model of insulin resistance or type 2 diabetes.

Absorptiometry, Photon↗
PubMedDate not supplied

The calcium channel blocker nitrendipine attenuates renal and glomerular hypertrophy in diabetic rats.

The efficacy of the calcium channel blocker nitrendipine in preventing early renal and glomerular hypertrophy and increased urinary albumin excretion (UAE) was studied in experimental diabetes in rats, starting treatment at the onset of diabetes. Female Wistar rats were randomised into four groups: diabetic and non-diabetic rats were given either placebo or nitrendipine (250 mg/kg) in the diet for 8 weeks. After 8 weeks the kidneys in the diabetic animals had increased significantly compared to the non-diabetic controls. In the diabetic nitrendipine-treated animals renal and glomerular hypertrophy was significantly smaller than in the diabetic placebo-treated group (p < 0.05). After an initial increment within the first week, the UAE remained constant throughout the study period in the diabetic nitrendipine-treated animals, while a steady increase was seen in the diabetic placebo-treated group (p < 0.05). No differences were seen in systemic blood pressure between calcium- channel-blocker-treated groups and placebo-treated groups. In conclusion, administration of nitrendipine to diabetic rats for 8 weeks had a significant inhibitory effect on renal and glomerular hypertrophy, and showed a tendency towards a reduction in UAE (p = 0. 06) without affecting metabolic control or systemic blood pressure.

Albuminuria↗
PubMed1994

Thiaproline reduces glomerular basement membrane thickness and collagen accumulation in the db/db mouse.

Glomerular basement membrane thickening and mesangial expansion are the main pathological features in diabetic nephropathy--glomerulosclerosis with the biochemical correlate of increased collagen accumulation. We studied a new principle to reduce collagen accumulation in the glomerulus: thiaproline, known to inhibit protein synthesis by blocking the elongation, led in our studies to a morphological reduction of the glomerular basement membrane thickening and to a decreased collagen content. As the thiaproline analogue is incorporated into collagen, the mechanism of increased degradation of the modified collagen is being discussed.

Animals↗
PubMed1991

White collar stress: what studies of physicians can teach us.

The impact of occupational stress on physicians and their medical practice has been subject to much debate but relatively little research. This paper reviews some recent studies concerning the psychosocial work environment of physicians. Psychiatric and cardiovascular epidemiologic data indicate that physicians are at similar or enhanced risk to socioeconomically comparative groups. Clinical studies of physicians reveal associations between psychosocial work characteristics and traditional cardiovascular risk factors. Further work is needed to enhance our understanding of the implication of present work environments on the health and well-being of physicians as well as other health care workers.

Blood Pressure↗
PubMedDate not supplied

Offspring of normal and diabetic rats fed saturated fat in pregnancy demonstrate vascular dysfunction.

BACKGROUND: Disturbances of the in utero environment may "program" for disease in later life. In this study, we determined whether dietary fat supplementation and/or diabetes in pregnancy can adversely affect vascular function in the offspring. METHODS AND RESULTS: Female Sprague-Dawley rats were fed a breeding diet or a diet high in saturated fat (30% wt/wt) for 10 days before mating, throughout pregnancy, and postpartum. Endothelium-dependent relaxation to acetylcholine was blunted in isolated femoral arteries of 15-day-old weanling pups from dams fed the 30%-fat diet. Endothelial dysfunction and enhanced constrictor responses to norepinephrine were also observed in an additional study of 60-day-old offspring of dams fed 20% saturated fat. Rats with streptozotocin-induced diabetes were also fed saturated fat during pregnancy. Femoral arteries from their 15-day-old offspring showed impairment of endothelium-dependent dilation and enhanced constrictor responses to norepinephrine and the thromboxane mimetic U46619 compared with young offspring of high-fat-fed normal dams. The 30%-fat diet was also deleterious to vascular function in the maternal diabetic animals when assessed in mesenteric arteries 16 days postpartum. CONCLUSIONS: A high-fat diet in pregnancy led to vascular dysfunction in rat weanlings and young adult offspring. Vascular function further deteriorated in weanlings if the maternal rat was diabetic.

Acetylcholine↗