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Glucose control is not improved by accelerating gastric emptying in patients with type 1 diabetes mellitus and gastroparesis. a pilot study with cisapride as a model drug.

The present pilot study investigated whether acceleration of gastric emptying in patients with type 1 diabetes and delayed gastric emptying (a possible cause of poorly controlled diabetes) improves long-term glucose control. Eight outpatients with diabetes (age 28-63 years, mean diabetes duration 24.6+/-6.0 years) and delayed gastric emptying of radio-opaque markers were randomised and treated, for three months each, with a prokinetic drug (cisapride 20 mg twice daily) and placebo. Mean capillary glucose, glucose variability (M-values, MAGE), fructosamine, and HbA1c were assessed. Gastric emptying of a solid standard meal was measured by scintigraphy after each treatment period. Chronic administration of a prokinetic drug resulted in improved solid gastric emptying (percentage residual) at 120 min (p=0.025). The percentage residual was 43.6+/-9.6 % during prokinetic treatment and 59.7+/-9.9 % during placebo (standard error of paired differences 5.7 %). The mean gastric emptying time (t/2) of solids was 88 min during prokinetic treatment compared to 113 min in the placebo arm (SE of paired differences 14 min; p=0.09). Mean blood glucose values (9.0+/-3.8 vs. 8.8+/-3.7 mmol/l), daily glucose variability (MAGE 6.8+/-1.3 vs. 6.3+/-1.6 mmol/l; M-value 15.2+/-2.5 vs. 13.9+/-4.5), and HbA1c at 3 months (7.8+/-1.1 % vs. 7.6+/-1.0 %) were not statistically different between prokinetic drug and placebo treatment. Similarly, the frequency of hypoglycaemic episodes (< or = 3 mmol/l) was not different in both groups (78 vs. 68). Our pilot study showed that long-term acceleration of gastric emptying had no effect on overall glycaemic control, the magnitude of glucose excursions, and hypoglycaemic episodes in patients with diabetic gastroparesis. We do not recommend, therefore, acceleration of gastric emptying as treatment strategy for "brittle diabetes" in patients with type 1 diabetes.

Adult↗

Lack of effect of captopril on glomerular hyperfiltration in normoalbuminuric normotensive insulin-dependent diabetic patients.

The aim of the present study was to evaluate the effects of captopril on the glomerular filtration rate (GFR) and urinary albumin excretion rate (UAER) of normoalbuminuric normotensive insulin-dependent diabetes mellitus (IDDM) patients with and without glomerular hyperfiltration. Eleven normoalbuminuric (UAER < 30 micrograms/min) patients (age: 34.3 +/- 4.6 years: diabetes duration: 9.5 +/- 6.4 years) participated in the study. Six patients were considered to be hyperfiltering (GFR > or = 134 ml/min/ 1.73m2). GFR (51Cr-EDTA single injection technique), extracellular volume (ECV; distribution volume of 51Cr-EDTA), UAER (RIA) and metabolic and biochemical parameters were measured at baseline, after 6 weeks on captopril (25 mg p.o. twice daily) and after 6 weeks off captopril. Plasma renin activity (PRA; RIA), plasma aldosterone (RIA) and blood volume (51Cr red cell labeled) were measured at baseline and after 6 weeks on captopril. The baseline clinical and laboratory characteristics of hyperfiltering and normofiltering IDDM patients were similar. GFR did not change during the study (144.1 +/- 28.8; 139.7 +/- 21.8; 132.8 +/- 29.9 ml/min/1.73 m2) either in patients with hyperfiltration (164.6 +/- 20.7; 153.8 +/- 18.3; 148.6 +/- 31.0 ml/min/1.73 m2; n = 6) or without hyperfiltration (119.6 +/- 11.1; 123.2 +/- 11.9; 113.8 +/- 14.4 ml/min/1.73 m2; n = 5). Also, ECV (22.2 +/- 3.6; 21.5 +/- 4.3; 21.5 +/- 3.5 L/1.73 m2), UAER (3.9 [0.4-22.1]; 4.0 [0.2-11.4]; 3.7 [2.0-26.2] micrograms/min), systolic (112 +/- 13; 105 +/- 10; 111 +/- 11 mmHg) and diastolic (76 +/- 12; 72 +/- 9; 73 +/- 12 mmHg) blood pressure did not change. No difference in blood volume (60.8 +/- 10.4; 62.3 +/- 8.4 ml/kg) or plasma aldosterone (10.4 +/- 4.9; 7.7 +/- 3.8 ng/dl) was observed between baseline values and values after captopril use. PRA increased (2.4 [0.4-22.1]; 12.9 [2.2-41.1]ng/ml/h) at the end of 6 weeks on captopril (P = 0.002). Fasting plasma glucose, glycated hemoglobin, fructosamine, plasma cholesterol and potassium, 24 h urinary urea and sodium were similar during the study. These results were unchanged when patients with and without hyperfiltration were analyzed as separate groups. From baseline to the end of 6 weeks on captopril there was no correlation between change in GFR and change in glycated hemoglobin (r = 0.02, P = 0.96), systolic (r = 0.23; P = 0.49) and diastolic (r = -0.32, P = 0.32) blood pressure, urinary urea (r = 0.21; P = 0.53) and UAER (r = -0.16; P = 1.00). In conclusion, captopril has no effect on the GFR and UAER of normoalbuminuric normotensive IDDM patients irrespective of the presence of glomerular hyperfiltration.

Adult↗

Insulin, insulin-like growth factor-1, and insulin resistance in women with pregnancy-induced hypertension.

OBJECTIVE: The purpose of this study was to assess insulin, insulin sensitivity, and insulin-like growth factor-I in women with preeclampsia and gestational hypertension. STUDY DESIGN: Insulin resistance was measured with the short insulin-tolerance test in 20 women with preeclampsia, in 18 women with gestational hypertension, and in 20 normotensive control subjects. Sex hormone binding globulin, insulin-like growth factor-I, glucose, fructosamine, glycosylated hemoglobin, insulin, C-peptide, and lipids were measured in the fasting state. RESULTS: Women with gestational hypertension had a significant lower insulin sensitivity index (0.13 +/- 0.1) and a higher level of insulin-like growth factor-I (333.71 +/- 107.6 ng/mL) than women in the control group (0.21 +/- 0.1 [P <.05]; 218.11 +/- 82.3 ng/mL [P <.01]) and women with preeclampsia (0.21 +/- 0.12 [P <.05]; 234.78 +/- 92.76 ng/mL [P <.01]). There were no significant correlations between insulin sensitivity index and insulin-like growth factor-I. CONCLUSION: Insulin resistance is present in women with gestational hypertension but not in women with preeclampsia and did not correlate with insulin-like growth factor-I.

Adult↗

Preprandial versus postprandial blood glucose monitoring in type 1 diabetic pregnancy: a randomized controlled clinical trial.

OBJECTIVE: This study was undertaken to compare preprandial and postprandial capillary glucose monitoring in pregnant women with type 1 diabetes. STUDY DESIGN: Sixty-one women with type 1 diabetes were randomly assigned at 16 weeks' gestation to preprandial or postprandial blood glucose monitoring using memory-based glucose reflectance meters throughout pregnancy. Serial measurements of hemoglobin A1c and fructosamine were obtained throughout pregnancy. Insulin, glucose, and insulin-like growth factor-I (IGF-I) were measured in cord blood at delivery. Neonatal anthropometric measures were performed within 72 hours of delivery RESULTS: Maternal age, parity, age of onset of diabetes, number of prior miscarriages, smoking status, social class, weight gain in pregnancy, and compliance with therapy were similar in the two groups. The postprandial monitoring group had a significantly reduced incidence of preeclampsia (3% vs 21%, P<.048), a greater success in achieving glycemic control targets (55% vs 30%, P<.001) and a smaller neonatal triceps skinfold thickness (4.5+/-0.9 vs 5.1+/-1.3, P=.05). CONCLUSION: Postprandial capillary blood glucose monitoring in type 1 diabetic pregnancy may significantly reduce the incidence of preeclampsia and neonatal triceps skinfold thickness compared with preprandial monitoring.

Adult↗

Alpha-glucosidase inhibition from a Chinese medical herb (Ramulus mori) in normal and diabetic rats and mice.

Alpha-glucosidase inhibitors are oral antidiabetic drugs. A traditional Chinese medical herb, Sangzhi (Ramulus mori), appears to have properties similar to those of alpha-glucosidase inhibitors. The effects of an aqueous extract of Shangzhi (SZ) were studied in normal and alloxan diabetic rats and mice, and these results compared with those for acarbose, an alpha-glucosidase inhibitor. In our grade-dose studies, SZ was found to lower and prolong the zenith of blood glucose concentration (ZBG) after sucrose or starch loading and stabilize blood glucose levels in fasting normal and alloxan diabetic mice. After 2 weeks of SZ administration with high-calorie chow or a normal diet, the fasting and non-fasting blood glucose concentrations in alloxan diabetic mice and rats were decreased. In alloxan rats, the blood fructosamine concentration was lowered. Results for acarbose and SZ were similar. These indicate that SZ has alpha-glucosidase inhibitory effects.

Alloxan↗

Effects of isomalt consumption on gastrointestinal and metabolic parameters in healthy volunteers.

The polyol isomalt (Palatinit) is a well established sugar replacer. The impact of regular isomalt consumption on metabolism and parameters of gut function in nineteen healthy volunteers was examined in a randomised, double-blind, cross-over trial with two 4-week test periods. Volunteers received 30 g isomalt or 30 g sucrose daily as part of a controlled diet. In addition to clinical standard diagnostics, biomarkers and parameters currently discussed as risk factors for CHD, diabetes or obesity were analysed. Urine and stool Ca and phosphate excretions were measured. In addition, mean transit time, defecation frequency, stool consistency and weight were determined. Consumption of test products was affirmed by the urinary excretion of mannitol. Blood lipids were comparable in both phases, especially in volunteers with hyperlipidaemia, apart from lower apo A-1 (P=0.03) for all subjects. Remnant-like particles, oxidised LDL, NEFA, fructosamine and leptin were comparable and not influenced by isomalt. Ca and phosphate homeostasis was not affected. Stool frequency was moderately increased in the isomalt phase (P=0.006) without changes in stool consistency and stool water. This suggests that isomalt is well tolerated and that consumption of isomalt does not impair metabolic function or induce hypercalciuria. In addition, the study data indicate that isomalt could be useful in improving bowel function.

Adult↗

Elimination of 14C-glycated albumin from serum of rabbit.

Glycated albumin was prepared by incubation of serum from rabbits with randomly labelled 14C-glucose. The isolated glycated albumin fraction was reinfused to the same animal. 14C-labelled glucose was given to alloxan-treated rabbits. The disappearance of the radioactivity showed a rapid initial phase and a slow elimination phase, which could be acceptably described by first-order kinetics. The estimated half-life of glycated albumin was about 6 days, which is about 70% of that generally stated for albumin in the rabbit. If these findings were transferred to human conditions, the half-life of fructosamine would be in the range of 13-14 days.

Animals↗

Whole cinnamon and aqueous extracts ameliorate sucrose-induced blood pressure elevations in spontaneously hypertensive rats.

OBJECTIVE: Many agents (nutrients, nutraceuticals, and drugs) that enhance insulin sensitivity and/or reduce circulating insulin concentrations lower blood pressure (BP). Recently, it was reported that cinnamon has the potential to favorably influence the glucose/insulin system. Accordingly, the purpose of the present study was to examine the effects of dietary cinnamon on systolic BP (SBP), and various glucose- and insulin-related parameters in spontaneously hypertensive rats (SHR). METHODS: In a series of three experiments, treated SHR eating sucrose and non sucrose containing diets were given various amounts of cinnamon, cinnamon extracts, or chromium. Then various parameters such as: body weight, systolic blood pressure, hematology and blood chemistries were followed for three to four weeks. RESULTS: Diets high in sucrose content are associated with insulin resistance and the elevation of SBP. Addition to diets of cinnamon (8% w/w) reduced the SBP of rats eating sucrose containing diets to virtually the same levels as SHR consuming non sucrose containing (only starch) diets. The presence of cinnamon in the diet also decreased the SBP of SHR consuming a non sucrose-containing diet, suggesting that cinnamon reduces more than just sucrose-induced SBP elevations--perhaps a genetic component(s) of the elevated BP as well. The effects of cinnamon on SBP tended to be dose-dependent. Cinnamon did not decrease the levels of blood glucose, but did lower circulating insulin concentrations. Aqueous extracts of cinnamon also decreased SBP and lowered the circulating levels of fructosamine. CONCLUSIONS: Cinnamon is used for flavor and taste in food preparation, but cinnamon may have additional roles in glucose metabolism and BP regulation. Therefore, BP regulation may not only be influenced favorably by limiting the amounts of dietary substances that have negative effects on BP and insulin function but also by the addition of beneficial ones, such as cinnamon, that have positive effects.

Animals↗

Body mass index and cardiovascular risk factors in Pacific Island Polynesians and Europeans in New Zealand.

OBJECTIVES: To examine relationships between body mass index (BMI) and cardiovascular risk factors in 279 Europeans and 231 Polynesian Pacific Islanders in New Zealand. METHODS: Participants were recruited from Seventh-Day Adventist church meetings or camps, and were surveyed by self-administered questionnaire. Blood pressure, weight and height were measured. Fasting blood samples were analysed for lipids, glucose and fructosamine. RESULTS: Age-adjusted BMI was higher in Pacific Islanders than in Europeans: 32.8(0.3) versus 25.6(0.3); means(SE); p = 0.0001). In Europeans, BMI was positively associated with systolic and diastolic blood pressures, triglycerides, total cholesterol, LDL cholesterol and fasting blood glucose, and negatively associated with HDL cholesterol. In Pacific Islanders, BMI was associated only with systolic and diastolic blood pressures, and with HDL cholesterol. These associations were stronger in Europeans than in Pacific Islanders. CONCLUSIONS: In this group of Pacific Islanders, the association between BMI and cardiovascular risk factors was weaker than in Europeans. This suggests that either BMI is a poor measure of adiposity in Pacific Islanders, or that adiposity may be less strongly linked to cardiovascular disease in Pacific Islanders.

Adult↗

Fructose diet-induced skin collagen abnormalities are prevented by lipoic acid.

Nonenzymatic glycation of proteins, leading to chemical modification and cross-linking are of importance in the pathology of diabetic complications. We studied the effect alpha-lipoic acid (LA) on the content and characteristics of the protein collagen from skin of high-fructose fed rats. The rats were divided into 4 groups of 6 each. Two groups of rats were fed with a high fructose diet (60 g/100 g diet) and administered either LA (35 mg/kg b.w., i.p) (FRU+LA) or 0.2 ml vehicle (saline) (FRU) for 45 days. The other 2 groups were fed with control diet containing starch (60 g/100 g diet) and administered either saline (CON) or lipoic acid (CON+LA). The rats were maintained for 45 days and then sacrificed. Plasma glucose, insulin, fructosamine, protein glycation, and blood glycated hemoglobin (HbA1C) were measured. Collagen was isolated from skin and the physicochemical properties of collagen were studied. Fructose administration caused accumulation of collagen in skin. Extensive cross-linking was evidenced by enhanced glycation and AGE-linked fluorescence. Increased peroxidation and changes in physicochemical properties such as shrinkage temperature, aldehyde content, solubililty pattern, susceptibility to denaturing agents were observed in fructose-fed rats. SDS gel pattern of collagen from these rats showed elevated beta component of type I collagen. These changes were alleviated by the simultaneous administration of LA. Administration of LA to fructose-fed rats had a positive influence on both quantitative and qualitative properties of collagen. The results suggest a mechanism for the ability of LA to delay diabetic complications.

Animals↗

DYN 12, a small molecule inhibitor of the enzyme amadorase, lowers plasma 3-deoxyglucosone levels in diabetic rats.

3-Deoxyglucosone (3DG) is a highly reactive alpha-dicarbonyl sugar and potent protein cross-linker that is important in the formation of advanced glycation end products (AGEs), which have been postulated to lead to the development of diabetic complications. (1) Reducing 3DG levels in diabetics is a potentially effective therapy to slow the development of diabetic complications. Standard biochemical methods were used to isolate, identify, and characterize the enzyme responsible for the production of 3DG, in order to develop an effective therapeutic agent against this target. We have purified and characterized Amadorase, a fructosamine-3-kinase, and demonstrated both in vitro and in vivo that it is responsible for the production of 3-deoxyglucosone (3DG). A small molecule inhibitor of Amadorase, DYN 12, significantly lowered plasma levels of 3DG in diabetic (by 46%, p = 0.0116) and normal (by 43%, p = 0.0024) rats. These data are the first indications that it is possible to significantly reduce 3DG production in diabetics and thus possibly reduce the development of diabetic complications.

Amino Acid Oxidoreductases↗

Serum 1,5-anhydroglucitol (GlycoMark ): a short-term glycemic marker.

1,5-Anhydroglucitol (1,5-AG), the 1-deoxy form of glucose, has been measured and used clinically in Japan for over a decade to monitor short-term glycemic control. Evaluation of glucose control otherwise requires measuring plasma glucose or glycated proteins whose levels reflect average glucose concentration over the half-life of the protein analyzed. Hemoglobin A1c measurements reflect blood glucose levels over that past 2-3 months, while fructosamine can be used to evaluate glycemic control over 10-14 days. In contrast, 1,5-AG levels in blood respond within 24 h as a result of glucose's competitive inhibition of 1,5-AG reabsorption in the kidney tubule. When glucose levels rise, even transiently, urinary loss of 1,5-AG occurs, and circulating levels fall. Because of changes in renal hemodynamics in normal pregnancies, 1,5-AG appears of limited usefulness in evaluation of gestational diabetes. However, the characteristics of 1,5-AG levels in patients with moderate to near-normal glycemic control suggest that it may be a valuable complement to frequent self-monitoring or continuous monitoring of plasma glucose to confirm stable glycemic control. Measurements performed daily or weekly in a given patient would suggest that overall glycemic control has been stable or improved if 1,5-AG levels are stable or increasing. If 1,5-AG levels fall, greater attention to glucose monitoring and both lifestyle and medical management could be prescribed to correct the glycemic excursions that would underlie such changes. The behavior of this analyte is different from all others used in the management of diabetes, creating potential opportunities for its use in clinical practice.

Biomarkers↗

The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial.

BACKGROUND: Preclinical studies have shown that the combination of chromium picolinate and biotin significantly enhances glucose uptake in skeletal muscle cells and enhances glucose disposal. The present pilot study was conducted to determine if supplementation with chromium picolinate and biotin can improve glycemic control in patients with type 2 diabetes mellitus with suboptimal glycemic control despite use of oral antihyperglycemic agents. METHODS: Forty-three subjects with impaired glycemic control (2-h glucose >200 mg/dL; glycated hemoglobin >or=7%), despite treatments with oral antihyperglycemic agents, were randomized to receive 600 microg of chromium as chromium picolinate and biotin (2 mg/day) (Diachrome(, Nutrition 21, Inc., Purchase, NY) in addition to their prestudy oral antihyperglycemic agent therapy. Measurements of glycemic control and blood lipids were taken at baseline and after 4 weeks. RESULTS: After 4 weeks, there was a significantly greater reduction in the total area under the curve for glucose during the 2-h oral glucose tolerance test for the treatment group (mean change -9.7%) compared with the placebo group (mean change +5.1%, P < 0.03). Significantly greater reductions were also seen in fructosamine (P < 0.03), triglycerides (P < 0.02), and triglycerides/ high-density lipoprotein cholesterol ratio (P < 0.05) in the treatment group. No significant adverse events were attributed to chromium picolinate and biotin supplementation. CONCLUSIONS: This pilot study demonstrates that supplementation with a combination of chromium picolinate and biotin in poorly controlled patients with diabetes receiving antidiabetic therapy improved glucose management and several lipid measurements. Chromium picolinate/ biotin supplementation may represent an effective adjunctive nutritional therapy to people with poorly controlled diabetes with the potential for improving lipid metabolism.

Adult↗

Importance of glycemic index in diabetes.

To date there are 11 medium to long-term studies that have specifically used the glycemic index (GI) approach to determine the clinical gains in diabetes or lipid management. All but one study produced positive findings. On average, low-GI diets reduced glycosylated hemoglobin by 9%, fructosamine by 8%, urinary C-peptide by 20%, and day-long blood glucose by 16%. Cholesterol was reduced by an average of 6% and triglycerides by 9%. These are modest improvements but so too were the changes to the diet. Unlike high-fiber diets, low-GI diets are "user friendly." As part of studies on the GI of foods, we determined the glycemic and insulin responses to 44 foods containing simple sugars. Their mean (+/- SE) GI was 62 +/- 14, which compares favorably with bread (GI = 73, glucose = 100). There was often no difference in the GI between the sweetened and unsweetened product. The time has come to reassess the value of GI in planning meals for diabetics.

Blood Glucose↗

Effects of a low-fat diet compared with those of a high-monounsaturated fat diet on body weight, plasma lipids and lipoproteins, and glycemic control in type 2 diabetes.

BACKGROUND: An important therapeutic goal for patients with type 2 diabetes is weight loss, which improves metabolic abnormalities. Ad libitum low-fat diets cause weight loss in nondiabetic populations. Compared with diets higher in monounsaturated fat, however, eucaloric low-fat diets may increase plasma triacylglycerol concentrations and worsen glycemic control in persons with type 2 diabetes. OBJECTIVE: We investigated whether, in type 2 diabetes patients, an ad libitum low-fat diet would cause greater weight loss than would a high-monounsaturated fat diet and would do this without increasing plasma triacylglycerol concentrations or worsening glycemic control. DESIGN: Eleven patients with type 2 diabetes were randomly assigned to receive an ad libitum low-fat, high-carbohydrate diet or a high-monounsaturated fat diet, each for 6 wk. The diets offered contained 125% of the estimated energy requirement to allow self-selection of food quantity. The response variables were body weight; fasting plasma lipid, lipoprotein, glucose, glycated hemoglobin A(1c), and fructosamine concentrations; insulin sensitivity; and glucose disposal. RESULTS: Body weight decreased significantly (1.53 kg; P < 0.001) only with the low-fat diet. Plasma total, LDL-, and HDL-cholesterol concentrations tended to decrease during both diets. There were no interaction effects between diet and the lipid profile response over time. Plasma triacylglycerol concentrations, glycemic control, and insulin sensitivity did not differ significantly between the 2 diets. CONCLUSION: Contrary to expectations, the ad libitum, low-fat, high-fiber diet promoted weight loss in patients with type 2 diabetes without causing unfavorable alterations in plasma lipids or glycemic control.

Blood Glucose↗

Calcium antagonists for treatment of diabetes-associated hypertension. Metabolic and renal effects of amlodipine.

In hypertensive diabetics a strict blood pressure control may decrease the incidence of cardiovascular and diabetic complications. Long-term experience with the use of calcium antagonists is still limited. The metabolic and renal effects of long-term (8 months) therapy with amlodipine, 5 to 10 mg daily, were studied in 15 hypertensive patients with uncomplicated diabetes mellitus as compared with 15 patients with essential hypertension. After a 4 week placebo phase, the diabetics and essential hypertensive patients did not differ in mean blood pressure (156/93 +/- 16/7 v 150/95 +/- 9/5 mm Hg), body weight, creatinine clearance, microalbumin excretion, and C-peptide and lipid levels, while serum fructosamine was higher in the diabetics. In both groups, amlodipine caused a significant and long-lasting decrease of arterial pressure (8%), but did not modify creatinine clearance, microalbumin excretion, and serum lipid levels. In diabetics indices of diabetic control and the insulin and glucose response to an oral glucose tolerance test were unchanged, whereas in essential hypertension the insulin response to a glucose load was decreased (P = .033). Amlodipine exerts a comparable and long-lasting antihypertensive effect in hypertensive diabetics and patients with essential hypertension. Despite the significant decrease in arterial pressure, there was no change in urinary microalbumin excretion. Lipid metabolism, quality of diabetic control, and the insulin response to a glucose load were not affected unfavorably.

Adult↗

The effect of ethanol on histone glycation in diabetic rats.

The glycation of liver histones was studied in rats with streptozotocin-induced diabetes, in ethanol (EtOH)-treated rats, and in EtOH-treated diabetic rats. In diabetes, the conditions of glucose-protein addition are more favourable extracellularly in serum and in erythrocytes than in the nucleus. This is indicated by the increased level of serum fructosamine and by the high level of glycated haemoglobin, while the glycation of intracellular histone is decreased. In the serum of diabetic rats, we found a relatively high acetaldehyde level, which resulted in elevated histone fluorescence. Fluorescence is an accepted marker of advanced glycation end-product (AGE), the intensity of which, according to our experiments is related not to the level of serum glucose, but to the level of acetaldehyde. The data obtained with histone proteins in diabetic rats treated with EtOH are in good agreement with the results of our earlier in vitro experimental results obtained with H1 histone: the reaction of the two aldehydes (glucose and acetaldehyde) in combination gives a lower glycohistone value than they do separately.

Acetaldehyde↗

Acute myocardial infarction in dogs with experimental diabetes.

OBJECTIVE: The aim was to examine whether diabetes interferes with the development of myocardial injury in a canine ischaemia-reperfusion model. METHODS: Non-insulin-requiring diabetes was induced in dogs by the streptozotocin-alloxan method. After 75 d, the dogs were anaesthetised and myocardial infarction was provoked by occluding the left anterior descending coronary artery for 2 h followed by 6 h reperfusion. RESULTS: Diabetic dogs had higher blood glucose [9.4(SEM 1) mmol.litre-1], fructosamine [417(57) mumol.litre-1], and glycated haemoglobin [3.3(0.7)%], than control dogs [5.5(0.6), p = 0.04, 243(15), p = 0.01, and 0.7(0.2), p = 0.003, respectively], and they also had higher serum lipids (p = 0.001) and platelet aggregation (p = 0.03). Area at risk was similar in diabetic and control dogs but in contrast to controls (r = 0.78, p = 0.007), area at risk and infarct size were not correlated in diabetics (r = 0.08). In both groups, collateral flow was the major determinant of infarct size: r = -0.73 in controls (p = 0.02) and -0.97 in diabetics (p = 0.001). In spite of higher subendocardial collateral flow in diabetics [representing 21.6(6)% of the flow in the corresponding non-ischaemic zone] than in controls [11.2(6)%], infarct size was similar in both groups. However, the mean observed infarct size in the diabetic group [7.5(2.8)% of the left ventricle] was significantly (p < 0.03) larger than the mean predicted infarct size [5.2(2)%]. Multivariate analysis confirmed that diabetes, as well as collateral flow, is an independent (p = 0.03) predictor of infarct size. CONCLUSIONS: For a given collateral flow, diabetic dogs develop larger infarcts than controls. Further studies are required to investigate the biochemical mechanism(s) underlying this deleterious effect. However, this may partly explain the poor prognosis of myocardial infarction in diabetic persons.

Animals↗