A randomised, controlled study of the effects of aerobic exercise and dietary fish on coagulation and fibrinolytic factors in type 2 diabetics.

Type 2 diabetes is associated with disturbances in coagulation and fibrinolysis. Prospective studies show that increased tissue plasminogen activator (tPA) antigen increases the risk of cardiovascular mortality. The present study examined the hypothesis that combining a regime of moderate aerobic exercise with one daily fish meal as part of a low-fat diet (30% total energy) would improve coagulation and fibrinolytic factors in dyslipidaemic type 2 diabetic patients. In a randomised. controlled, 8-week trial, 55 sedentary type 2 diabetic subjects with serum triglycerides >1.8 mmol/l and/or HDL-C <1.0 mmol/l were randomly assigned to a low-fat diet (30% daily energy intake) with or without one fish meal daily (3.6 g omega3 fatty acids/day) and further randomized to a moderate (55-65% VO2max) or light (heart rate <100 bpm) exercise program. Plasma levels of fibrinogen, coagulation factor VIIc, tPA and plasminogen activator inhibitor (PAI-1) antigen were measured before and after intervention. In the 49 subjects who completed the study, the fish diet alone, moderate exercise alone and the combination of fish and moderate exercise all led to significant reductions in tPA antigen concentrations (-2.1 ng/ml, p = 0.02. -1.9 ng/ml, p = 0.03, -2.0 ng/ml, p = 0.01, respectively) compared to controls. In multivariate regression, changes in fasting blood glucose (positively) and erythrocyte omega3 fatty acid composition (inversely) were independent predictors of the change in tPA antigen. The fish diet alone contributed to a significant rise in coagulation factor VIIc compared to controls (4.9%, p = 0.02), which was prevented by moderate exercise. No significant effects on PAI-1 antigen and fibrinogen were seen. In view of recent epidemiological findings, the reduction in tPA antigen with both fish and moderate exercise in these dyslipidaemic type 2 diabetic patients could reflect a reduced thrombotic potential and decreased cardiovascular risk. Furthermore, a small, albeit significant, increase in coagulation factor VIIc associated with fish can be prevented by a concomitant programme of moderate exercise.

Effects of a short-term circuit weight training program on glycaemic control in NIDDM.

This study assessed the effects of short-term circuit weight training (CWT) on glycaemic control in NIDDM. Twenty-seven untrained, sedentary subjects (mean age, 51) with NIDDM participated in an 8-week randomised, controlled study, involving either CWT 3 days/week (n = 15) or no formal exercise (control) (n = 12). All subjects performed regular self-blood glucose monitoring throughout. Fasting serum glucose and insulin were measured following a 12-h fast and during an oral glucose tolerance test (75 g) before and after 8 weeks. Twenty-one subjects completed the study (CWT, n = 11) (Control, n = 10). Strength for all exercises improved significantly after CWT. Pooled time-series analysis, using a random effects model, revealed an overall decrease in self-monitored glucose levels with CWT compared to controls. Significant reductions from baseline values were observed in both the glucose (-213 mmol l-1 per 120 min, P < 0.05) and insulin (-6130 pmol l-1 per 120 min, P < 0.05) area under the curve following CWT relative to controls. After adjustment for body mass changes, the change in self-monitored glucose levels and insulin area under the curve, but not glucose area under the curve, remained significant. Short-term CWT therefore may provide a practical exercise alternative in the lifestyle management of this condition.

Decreased tPA with exercise training and dietary fish in NIDDM - Poster Presentation

We assessed the effects of combining moderate exercise training with one daily fish meal as part of a low-fat diet (30 percent total energy) on coagulation and fibrinolytic factors in dyslipidaemic NIDDM patients. In a randomised, controlled, 8-week trial, 55 sedentary NIDDM subjects were assigned to a low-fat diet (30 percent daily energy intake) with or without one fish meal daily (3.6 g W3 fatty acids/day) and further randomised to a moderate (55-65 percent VO 2max) or light heart rate < 100 bpm) exercise programme. In the 49 subjects who completed the study, the fish diet alone, moderate exercise and the combination of fish and moderate exercise all significantly reduced tPA antigen concentrations compared to controls. Changes in fasting blood glucose levels (positively) and erythrocyte w3 fatty acid composition (inversely) were independent predictors of tPA change. Compared to controls, the fish diet alone contributed to a significant rise in factor VIIc but this was prevented by the addition of moderate exercise training, combined with regular fish meals within a low-fat diet, could favour a reduced thrombotic potential and cardiovascular risk in these dyslipidaemic NIDDM patients.(AU)

The independent and combined effects of aerobic exercise and dietary fish intake on serum lipids and glycemic control in NIDDM. A randomized controlled study.

OBJECTIVE: The triglyceride-lowering effects of omega-3 fats and HDL cholesterol-raising effects of exercise may be appropriate management for dyslipidemia in NIDDM. However, fish oil may impair glycemic control in NIDDM. The present study examined the effects of moderate aerobic exercise and the incorporation of fish into a low-fat (30% total energy) diet on serum lipids and glycemic control in dyslipidemic NIDDM patients. RESEARCH DESIGN AND METHODS: In a controlled, 8-week intervention, 55 sedentary NIDDM subjects with serum triglycerides > 1.8 mmol/l and/or HDL cholesterol < 1.0 mmol/l were randomly assigned to a low-fat diet (30% daily energy intake) with or without one fish meal daily (3.6 g omega-3/day) and further randomized to a moderate (55-65% VO2max) or light (heart rate < 100 bpm) exercise program. An oral glucose tolerance test (75 g), fasting serum glucose, insulin, lipids, and GHb were measured before and after intervention. Self-monitoring of blood glucose was performed throughout. RESULTS: In the 49 subjects who completed the study, moderate exercise improved aerobic fitness (VO2max) by 12% (from 1.87 to 2.07 l/min, P = 0.0001). Fish consumption reduced triglycerides (0.80 mmol/l, P = 0.03) and HDL3 cholesterol (0.05 mmol/l, P = 0.02) and increased HDL2 cholesterol (0.06 mmol/l, P = 0.01). After adjustment for age, sex, and changes in body weight, fish diets were associated with increases in GHb (0.50%, P = 0.05) and self-monitored glucose (0.57 mmol/l, P = 0.0002), which were prevented by moderate exercise. CONCLUSIONS: A reduced fat diet incorporating one daily fish meal reduces serum triglycerides and increases HDL2 cholesterol in dyslipidemic NIDDM patients. Associated deterioration in glycemic control can be prevented by a concomitant program of moderate exercise.

Microalbuminuria in type 2 diabetes: an independent predictor of cardiovascular mortality.

BACKGROUND: Microalbuminuria has been shown to be associated with cardiovascular mortality in type 2 diabetic subjects. It is unclear to what extent this is due to the increased prevalence of other cardiac risk factors. AIMS: To examine the relationship of urine albumin excretion to cardiovascular mortality and to determine its status as an independent risk factor. METHODS: In a prospective longitudinal study from 1986-1993 we followed 666 type 2 diabetic subjects from a diabetes outpatient service. Cardiovascular risk factors including urine albumin concentration were measured at study entry. Cox proportional hazards regression was used to determine risk factors for mortality. The hazard ratios of microalbuminuria and macroalbuminuria for all cause, cardiovascular and coronary heart disease mortality were determined after accounting for other cardiac risk factors including blood pressure, glycated haemoglobin, total cholesterol, HDL cholesterol, triglycerides, urea, smoking, body mass index, patient age and disease duration. RESULTS: The prevalence of urine albumin of 30-300 mg/L at study entry was 31.7%. A total of 167 deaths occurred (80 from cardiovascular disease). Mortality hazard ratios in subjects with urine albumin of 30-300 mg/L as compared to < 30 mg/L, adjusted for age, sex and other cardiovascular risk factors were 1.77 (95% CI 1.22-2.57, p = 0.002) for all causes, 2.34 (95% CI 1.38-3.99, p = 0.002) for cardiovascular and 1.78 (95% CI 0.97-3.26, p = 0.061) for coronary heart disease (CHD) mortality. Other factors significantly associated with cardiovascular mortality included diastolic blood pressure, HDL cholesterol and glycated haemoglobin. Total cholesterol and log triglyceride were significantly associated with CHD mortality. Disease duration, age at diagnosis, smoking and body mass index were not related to cardiovascular or CHD mortality. CONCLUSIONS: We confirm microalbuminuria as an independent predictor of mortality in type 2 diabetes despite its association with a number of conventional cardiovascular risk factors.

Absence of increased susceptibility of LDL to oxidation in type 1 diabetics.

Insulin-dependent diabetics have a greatly increased risk of developing premature coronary artery disease which is not entirely explained by known risk factors. A possible explanation may be enhanced oxidative modification of low density lipoprotein (LDL). The aim of this study was to determine firstly, whether or not LDL from moderately well controlled type 1 diabetics is more readily oxidisable than LDL from healthy non-diabetics and, secondly, to assess whether potential predictors of LDL oxidisability differ between type 1 diabetics and controls. Twenty type 1 diabetic men were carefully matched with healthy non-diabetic men on the basis of age and body mass index and each pair attended the department on the same morning for blood sampling. LDL oxidisability was assessed using both copper in PBS, 15 and 30 mM glucose, and with AAPH. There was no difference between type 1 diabetics and controls in the susceptibility of the LDL to either copper-dependent or non-transition metal-dependent oxidation. Furthermore, there was no difference between the groups for LDL vitamin E content, LDL fatty acid composition in cholesteryl esters, triglycerides or phospholipids, or LDL copper reductive capacity, but LDL glycation was elevated in the IDDM subjects. Given the absence of increased LDL oxidisability in these subjects, the recommendation of vitamin E supplementation in type 1 diabetics should be considered a secondary priority to achieving adequate glucose control.

Mortality and coronary heart disease in diabetes mellitus.

A clinic-based study of 1,063 patients with Type 2 diabetes recruited from 1973 to 1982 identified 533 deaths (attributed to coronary heart disease in 268 cases) by 31 December 1989. When compared to the general population of Australia the overall standardised mortality ratio was 1.42 (95 per cent confidence interval (CI) 1.26 to 1.58) for females and 1.19 (CI 1.03 to 1.35) for males. Cox regression analysis showed that having coronary heart disease or absence of foot pulses at the time of entrance to the study were the major independent risk factors for overall mortality after adjustment for initial age. Elevated cholesterol and blood pressure were found to be major independent risk factors for death from coronary heart disease.

Type 1 diabetes and latent pernicious anaemia.

OBJECTIVE: To determine the prevalence of latent pernicious anaemia (PA) in Type 1 diabetics. DESIGN: Patients with Type 1 diabetes were screened at two yearly intervals on a continuing basis. SETTING: Diabetic Unit, Royal Perth Hospital, Western Australia. PATIENTS: Three hundred and seventy-one patients, 156 females and 215 males, attending a diabetic clinic. They were classified as having Type 1 diabetes on the basis of age of onset less than 40 years and requiring insulin from the start. MAIN OUTCOME MEASURES: Serum cobalamin levels were measured and studies of thyroid function and a blood count were done. Patients with a reduced serum level of cobalamin had tests for cobalamin absorption. RESULTS: Six patients had a low serum cobalamin level; five showed malabsorption of the vitamin which could be corrected by the addition of intrinsic factor. Four of these patients had no clinical signs of PA. The fifth was mildly anaemic (haemoglobin level 111 g/L) and had megaloblastic bone marrow. He was classified as having frank PA. The sixth patient was not available for further testing. These results give a prevalence of latent PA of 11 per 1000 in Type 1 diabetics, compared with 3.9 per 1000 in diabetics with clinically manifest disease and 1.27 per 1000 in the general population. All four patients with latent PA had hypothyroidism, based on low thyroxine levels, increased levels of thyroid stimulating hormone and the presence of thyroid antibodies. CONCLUSION: Latent PA is not uncommon in Type 1 diabetics. It has a long preclinical course and occurs in those patients with thyroid disease. The screening of Type 1 diabetics for latent PA has worthwhile benefits as a "preventive" health measure.

Dietary fish oils increase serum lipids in insulin-dependent diabetics compared with healthy controls.

The effect of daily dietary supplementation with fish oil on serum lipids and platelet total phospholipid fatty acids was examined in male normolipidemic insulin-dependent diabetics and normal controls. They were given 15 g/d of fish oil as Max EPA (equivalent to 2.7 g/d of eicosapentaenoic acid) for 3 weeks. The diabetics showed a rise in total cholesterol, attributable to increases in LDL- and HDL-cholesterol. The increase in HDL-cholesterol was largely due to a rise in its HDL2 subclass. There was also a decrease in triglycerides in both groups. Similar changes in lipids were seen in the normal controls, although these were not significant. The more pronounced effect in diabetics suggests an altered metabolic response to omega-3 fatty acids in that disorder. However, the results indicate that the possible detrimental effect of the rise in total and LDL-cholesterol following fish oil may be offset by the increase in the protective HDL2 subclass.

Serum lipids in insulin-dependent diabetics are markedly altered by dietary fish oils.

1. The effect of dietary fish oil supplementation on serum lipids was examined in normolipidaemic insulin-dependent male diabetics and healthy controls. Fish oil was given as Max eicosapentaenoic acid (EPA), 15 g daily (equivalent to 2.7 g/day of EPA) for 3 weeks. 2. There was a substantial increase in EPA but a depletion of arachidonic acid content of platelet phospholipids. 3. Diabetics showed a rise in total cholesterol, attributable to increases in low density and high density lipoprotein (LDL and HDL) cholesterol. The rise in HDL cholesterol was largely due to an increase in its HDL2 subclass. Similar changes were found in the healthy men although these were not as marked. A decrease in triglycerides was observed in both diabetics and normal controls. 4. Generally, diabetics showed greater changes in lipid concentrations which may suggest an altered metabolic response to w3 fatty acids. Therefore, the possible detrimental effect of the rise in total cholesterol and LDL cholesterol following fish oil administration may be offset by the increase in the protective HDL2 subclass.

Hypercholesterolaemic effect of fish oil in insulin-dependent diabetic patients.

The effect of the daily administration of Max EPA fish oil (equivalent to 2.7 g per day of eicosapentaenoic acid) on serum lipid levels was examined in insulin-dependent male diabetic patients with cholesterol levels of less than 6.5 mmol/L. After three weeks of fish-oil supplementation there was a significant rise in total cholesterol levels, which was due largely to increases in low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)- cholesterol levels. The increase in HDL-cholesterol levels was accounted for by its HDL2 subclass. There was a decrease in serum triglyceride levels, but this was also observed in a control group of diabetic patients who did not receive fish oil and is probably explained by weight loss in this group. Similar changes in lipid levels were found in a subgroup of diabetic patients with retinopathy. The possible detrimental effect of the increase in total cholesterol and LDL-cholesterol levels after Max EPA fish oil at this dose may be offset by the selective rise in the protective HDL2 subclass.

Prevalence of diabetic complications in relation to risk factors.

The prevalence of diabetic complications is reported from a cross-sectional study of rural diabetic subjects in Western Australia. Logistic-regression analysis has been used to discover potential risk factors associated with each complication. A distinction has been made between time-related variables (age, age at diagnosis, duration of diabetes) and other risk variables. We have attempted to identify the major time-related risk variables for each complication and then examined the effect of other risk variables after accounting for the major time-related variables. The important time-related variables were found to be duration of diabetes for retinopathy, age for macrovascular disease, duration and age at diagnosis of diabetes for sensory neuropathy, and age for renal impairment. When matched on these important time-related variables, the overall prevalences of complications for insulin-dependent (IDDM) compared with non-insulin-dependent (NIDDM) diabetic patients were essentially the same. An exception is renal impairment, for which IDDM patients had a higher prevalence than did NIDDM patients of the same age. After allowing for time-related variables, the analysis also demonstrates positive independent associations between diabetic control (glycosylated hemoglobin) and retinopathy and between diabetic control and macrovascular disease. Plasma cholesterol (positively) and high-density lipoprotein cholesterol (negatively) were related independently to both macrovascular disease and renal impairment. Very few differences in the risk-factor profiles for complications were found for IDDM compared with NIDDM patients after allowing for time-related variables.

Diabetes in part-aborigines of Western Australia.

One thousand, two hundred and eighteen diabetic subjects living in and around country towns of Western Australia were screened for complications of diabetes. This population included 134 subjects of Aboriginal descent, who were compared with the Caucasoids taking part. In the Aboriginal group there was a greater proportion of Type 2 (non-insulin-dependent) diabetic patients, a relative female preponderance (69% compared with 51%) and a tendency to present at an earlier age of onset than their Caucasoid counterparts. Diabetic complications were at least as common in the Aboriginal group as in the Caucasoid patients. Indeed, retinopathy within 10 years of onset of diabetes was more common in the Aborigines. Peripheral neuropathy was more prevalent in Aborigines treated by diet alone or oral hypoglycaemic agents than in Caucasoids. A much greater prevalence of proteinuria was an additional feature of the Aboriginal subgroup (29% versus 4%).

The relationship between the control of diabetes mellitus and circulating glycosylated haemoglobin A1.

The mean glycosylated haemoglobin A1 level in 200 diabetics, 13.2%+/-2.6 (1SD), was nearly twice the level found in 100 non-diabetics, 7.42%+/-0.6 (1SD), and overlap between the two populations was minimal. Glycosylated haemoglobin A1 levels, fasting and two hour post-prandial blood glucose concentrations and 24 hour urinary glucose excretion were measured at intervals over a period of 12 weeks in six diabetics requiring stabilisation. A close correlation was found between glycosylated haemoglobin A1 levels and short term parameters of control.