Research Database –
International Updates

Diabetes

Issue 93

DAVISON and co-workers, School of Applied Medical Sciences and Sports Studies, University of Ulster Jordanstown, Belfast, UK, have studied exercise, free radicals, and lipid peroxidation in type I diabetes mellitus.
Background: It has been suggested that type I diabetes mellitus patients are more susceptible to resting and exercise-induced oxidative stress than healthy people, but to date there is no direct evidence that these patients have elevated levels of free radical species. The aim of this study was to investigate the levels of free radical species pre and post exercise in the venous blood of young men with type I diabetes mellitus, and to compare them with the same values in healthy young men.
Methods: Electron Spin Resonance (ESR) spectroscopy was used to measure free radicals in venous blood of young men, both type I diabetic ones and matched controls. Supporting measures of lipid peroxidation, ambient blood glucose and selected antioxidants were also measured.
Results: Diabetes patients presented with greater concentrations of free radicals and lipid hydroperoxides compared to healthy controls (p = 0.05). There were no differences in other measures for lipid peroxidation. Vitamin E levels were lower in diabetics due to a large decrease during exercise (p = 0.05).
Conclusions: The authors suggest that the greater concentrations of free radicals found in diabetics are due to increased glucose auto- oxidation and/or a lower exercise-induced oxidation rate of the major antioxidant, vitamin E. The free radicals are thought to be secondary species derived from decomposition of lipid hydroperoxides.
Davison GW, George L, Jackson SK, Young IS, Davies B, Bailey DM, Peters JR, Ashton T. Exercise, free radicals, and lipid peroxidation in type I diabetes mellitus. Free Radical Biology and Medicine 33 (11): 1543-1551, Dec 1, 2002.

Issue 89

HALLIWELL, Department of Biochemistry, Faculty of Medicine, National University of Singapore, MD 7 #03-15, 8 Medical Drive, Singapore 117597, bchbh@nus.edu.sg, has reviewed (88 references) vitamin E and the treatment and prevention of diabetes.
Background: Diabetes is accompanied by oxidative stress, especially seen as lipid peroxidation, due to increased oxygen free radical production. This results in part from hyperglycaemia, but it may also precede and accelerate the development of type 2 diabetes and its complications.
Results: Epidemiological evidence suggests that low vitamin E intake is a risk factor for the development of type 2 diabetes, and small scale intervention studies have demonstrated a benefit of vitamin E for epithelial function, retinal blood flow, and renal dysfunction (all common sequelae of type 2 diabetes). Animal studies also support the usefulness of vitamin E.
Conclusions: The available evidence suggests that a major double-blinded controlled clinical trial of antioxidants in the prevention and treatment of type 2 diabetes should be undertaken in order to develop strategies to delay the onset and ameliorate the sequelae of this disease.
Halliwell B. Vitamin E and the treatment and prevention of diabetes: a case for a controlled
clinical trial. Singapore Medical Journal 43 (9): 479-484, Sep 2002.

Issue 88

MULLEN and colleagues, Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, Northern Ireland, brian@mullen99.fsnet.co.uk, showed that ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes.
Background: Experimental evidence suggests that acute parenteral administration of high-dose ascorbic acid (vitamin C) has beneficial vascular effects in type 2 diabetes. In this study, the haemodynamic effects of chronic oral supplementation were examined.
Methods: 30 diabetes type 2 patients aged 45 to 70 were randomly assigned in a double-blinded manner to receive either 500 mg ascorbic acid daily by mouth, or a placebo. Patients were studied at baseline and after 4 weeks of treatment. The central aortic augmentation index (AgIx) and the time to wave refraction (Tr) were derived from radial artery pulse wave analysis. AgIx and Tr were used as measures for systemic arterial stiffness and aortic stiffness, respectively.
Results: Ascorbic acid reduced brachial systolic blood pressure from 142.1 ± 12.6 to 132.3 ± 12.1 mm Hg (p = 0.01), brachial diastolic pressure from 83.9 ± 4.8 to 79.5 ± 6.9 mm Hg (p = 0.01), and AgIx from 26.8 ± 5.5% to 22.5 ± 6.8 % (p = 0.01). Tr increased from 137.1 ± 12.6 to 143.4 ± 9.2 ms (p = 0.01). Placebo had no haemodynamic effects.
Conclusions: The study shows that after one month, oral vitamin C supplementation lowered arterial blood pressure and improved arterial stiffness in patients with type 2 diabetes. Ascorbic acid supplementation may therefore be a useful and inexpensive adjunctive
therapy for type 2 diabetes.
Mullen BA, Young IS, Fee H, McCance DR. Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes. Hypertension 40 (6): 804-809, Dec 2002.

Issue 86

JAIN and colleagues, Department of Medicine, MAMC and Associated Lok Nayak and GB Pant Hospitals, New Delhi, describe the effects of low-dose omega-3 fatty acid substitution in type 2 diabetes.

Background: A state of increased oxidative stress has been recognized in type 2 diabetes mellitus. This study was done in order to assess the effects of omega-3 fatty acids on this state of oxidative stress.

Methods: In this prospective preliminary study, 65 patients with type 2 diabetes mellitus and 30 healthy controls were evaluated for blood glucose, blood pressure, lipid profile, and oxidative stress (as measured by lipid peroxides, diene conjugates, and reduced glutathione in serum). 40 diabetes patients were randomly divided into two groups. One group were prescribed a diabetic diet plus a placebo. The other group were prescribed a diabetic diet plus 180 mg of eicosapentaenoic acid and 120 mg of docosahexaenoic acid twice daily. After 6 weeks all parameters were reassessed.

Results: The measured biochemical parameters showed a significant elevation of oxidative stress in the type 2 diabetes patients as compared to healthy controls. After 6 weeks, the oxidative stress parameters had improved in both groups but significantly more so in the omega-3 fatty acids group. Patients in this group also showed better values for glycaemic status, blood pressure and lipid profile.

Conclusions: This study shows that people suffering from type 2 diabetes mellitus are exposed to elevated oxidative stress which can be improved by addition of low levels of omega-3 fatty acids to their diet. Moreover, blood pressure and metabolic profile improve under such a regimen.

Jain S, Gaiha M, Bhattacharjee J, Anuradha S, et al. Effects of low-dose omega-3 fatty acid substitution in type-2 diabetes mellitus with special reference to oxidative stress: a prospective preliminary study. Journal of the Association of Physicians of India 50: 1028-1033, Aug 2002.

WOODMAN and co-workers, Department of Medicine, The University of Western Australia, Perth, Australia, rwoodman@cyllene.uwa.edu.au, measure the effects of purified omega-3 fatty acids on glycaemic control, blood pressure, and serum lipids in type 2 diabetes patients.

Background: Omega-3 fatty acids lower blood pressure, improve lipids, and benefit other cardiovascular disease risk factors. The aim of this study was to determine their effects on insulin sensitivity, stimulated insulin secretion, blood pressure, and serum lipids in type 2 diabetes mellitus patients treated for hypertension.

Methods: Randomized double-blinded placebo-controlled trial of 59 patients who were randomly assigned to consume 4g of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or olive oil per day for 6 weeks in addition to their usual diet.

Results: Fasting glucose increased in both the EPA and SHA groups as compared to the olive oil (control) group. Neither EPA nor DHA had any significant effects on glycated hemoglobin, fasting insulin or C- peptide, insulin sensitivity or secretion, or blood pressure. Serum triglycerides in the EPA and DHA groups decreased. No significant changes in serum total, LDL, or HDL cholesterol were found.

Conclusions: The omega-3 fatty acids studied here had beneficial effects on lipid profile but adverse effects on short-term glycaemic control in diabetic patients. The overall implications for cardiovascular disease require long-term study.

Woodman RJ, Mori TA, Burke V, Puddey IB, Watts GF, Beilin LJ, et al. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. The American Journal of Clinical Nutrition 76 (5): 1007-1015, Nov 2002.

Comment: This first study above found that the addition of low levels of omega-3 fatty acids to the diets of diabetics was beneficial to blood pressure and metabolic profile; the second study by Woodman et al found that omega-3 fatty acids benefitted the lipid profile, but had adverse effects on short term glycaemic control. Hopefully this different outcomes will be resolved in due course.

Issue 69

RYAN and colleagues, Department of Medicine, Division of Endocrinology and Metabolism, Muttart Diabetes Research, and Training Centre and Perinatal Research Centre, University of Alberta, Edmonton, Alberta, Canada, edmond.ryan@ualberta.ca, surveyed the usage of prescribed medication, over-the-counter (OTC) supplements and alternative medicines in diabetic and control subjects.
Background: Despite enormous advances in [allopathic] medical care, increasing numbers of people are still using herbal or other alternative remedies. People with chronic conditions such as diabetes may turn to alternative remedies purported to improve glycaemic control.
Methods: This was a prospective, case-control study. 502 diabetic subjects and 201 controls were contacted in person or by telephone and asked to provide details about themselves, their diabetes (for diabetic subjects), and their use of prescribed medication, OTC supplements and alternative medications. Subjects were asked to rank their assessment of the effectiveness of each medication. Costs were calculated on a per-month basis from average prices obtained from five alternative health stores and five chemist shops.
Results: 78% of diabetic subjects were taking prescribed medication for their diabetes, 44% were taking OTC supplements and 31% were taking alternative medicines. 63% of control subjects were taking prescribed medication, 51% were taking OTC supplements and 37% were taking alternative medicines. The most common OTC supplements were multivitamins, vitamin E, vitamin C, calcium and aspirin. The most common alternative medications were garlic, echinacea, herbal mixtures and glucosamine. Chromium was only (and rarely) used by diabetic subjects. Alternative medicines purported to have hypoglycaemic effects were little used by diabetic subjects. The effectiveness of alternative medicines was rated significantly lower than that of prescribed medications, but subjects still thought them efficacious. Diabetic subjects spent almost as much money on OTC supplements and alternative medications as they did on their diabetic medications.
Conclusion: A third of people, both diabetic and non-diabetic, were taking alternative medications they considered efficacious. Money spent on alternative and OTC supplements nearly equalled that spent on prescription medications. Evaluation of these remedies and their merits is thus long overdue.
Ryan EA et al. Use of alternative medicines in diabetes mellitus. Diabetic Medicine 18 (3): 242-5. Mar 2001.

Comment: I wonder what would happen if suddenly all health professionals from all sectors – allopathic and complementary – would start working together toward improving the health of their patients instead of trying to prove that patients were either wasting their money or potentially harming themselves by eating garlic or taking herbs such as echinacea. Can you spot the agenda for this research?

CHRISTENSEN and colleagues, Department of Nephrology, Aalborg Hospital, Aalborg, Denmark, jhc@dadlnet.dk, examined associations between n-3 polyunsaturated fatty acids (PUFA) and 24-hour heart rate variability (HRV) in patients with type 1 and type 2 diabetes mellitus (DM).
Background: Dietary PUFA derived from fish may reduce the incidence of sudden cardiac death (SCD).
Methods: This was an observational study conducted at the outpatients’ diabetic clinic at Hjoerring Hospital, Hjoerring, Denmark. 43 patients with type 1 DM and 38 with type 2 DM completed a food questionnaire regarding fish consumption, and their platelet content of n-3 PUFA and 24-hour HRV were measured.
Results: Patients’ fish consumption was strongly related to their platelet n-3 PUFA content. In addition, patients with type 1 DM showed a close positive association between platelet n-3 PUFA content and 24-hour HRV (this association was not significant in patients with type 2 DM).
Conclusion: The findings may indicate a beneficial effect of n-3 PUFA on HRV in patients with type 1 DM. Further studies are warranted to investigate whether supplementation with n-3 PUFA reduces the risk of SCD amongst patients with DM.
Christensen JH et al. Heart rate variability and n-3 polyunsaturated fatty acids in patients with diabetes mellitus. Journal of Internal Medicine 249 (6): 545-52. Jun 2001.

Issue 68

MANZELLA and colleagues, Department of Geriatric Medicine and Metabolic Diseases, Second University of Naples, Italy, investigated the possible effects of vitamin E supplementation on the cardiac autonomic nervous system in patients with type 2 diabetes (T2D) and cardiac autonomic neuropathy.
Background: T2D is associated with elevated oxidative stress and declines in antioxidant defence. In T2D, there is also an imbalance in the ratio of cardiac sympathetic to parasympathetic autonomic tone. Antioxidants, particularly vitamin E, might benefit the cardiac autonomic nervous system by decreasing oxidative stress.
Methods: In this double-blind, randomised, controlled trial, 50 patients with T2D received either vitamin E (600 mg/day) or placebo for 4 months. Cardiac autonomic function was assessed by analysis of heart rate variability (HRV).
Results: Patients in the vitamin E group showed decreases in levels of glycated haemoglobin, plasma insulin, norepinephrine and epinephrine; a lower homeostasis model assessment (HMA) index; improved indices of oxidative stress; increases in the R-R interval, total power and the high-frequency component (HF) of HRV; and decreases in the low-frequency (LF) component of HRV and the ratio of LF to HF. The change in plasma vitamin E concentration correlated with the change in LF/HF ratio (r=-0.43) independently of changes in the HMA index and plasma catecholamine concentrations.
Discussion: Daily vitamin E supplementation (600 mg) for 4 months improved the ratio of cardiac sympathetic to parasympathetic tone in patients with T2D. This effect might be mediated by a decline in oxidative stress.
Manzella D et al. Chronic administration of pharmacologic doses of vitamin E improves the cardiac autonomic nervous system in patients with type 2 diabetes. American Journal of Clinical Nutrition 73 (6): 1052-7. Jun 2001.

Issue 51

Comments: This interesting study demonstrates that antioxidants modulate, at the molecular level, the enhanced expression of insulin genes, via insulin mRNA, as well as a beta-cell-specific transcription factor. Good news eventually for diabetics.

Issue 34

PREUSS and colleagues, Department of Medicine, Georgetown University Medical Center, Washington DC 20007 USA studied, in spontaneously hypertensive rats (SHR), the effects upon systolic blood pressure (SBP) of ingesting 3 modulators of insulin metabolism: chromium polynicotinate, bis(maltolato)oxovanadium (BMOV) and the herb Gymnema sylvestre.
Methods: In one study, SHR were fed either a starch, sugar or sugar diet containing chromium polynicotinate, bis(maltolato)oxovanadium (BMOV) or Gymnema sylvestre. Tail SBP was estimated indirectly, blood chemistries measured, and thiobarbituric acid reacting substances (TBARS) formation, a measure of lipid peroxidation, determined in liver and kidney tissue. In a second study, SBP was measured in SHR fed diets with differing concentrations of BMOV.
Results: Compared with starch, SHR fed sucrose demonstrated, within days, a significant elevation of SBP which was maintained throughout the study. The addition of chromium polynicotinate to the sucrose diet at the start of the study prevented sucrose-induced elevation of SBP for 2 weeks; thereafter SBP rose significantly. High concentrations of BMOV overcame the sucrose-induced SBP rise and also lowered SBP below levels observed in SHR fed the starch diet; however, there was a marked weight loss. In the second study which looked at effects of differing concentrations of BMOV, even at the 0.01% w/w concentration of BMOV, SBP was still significantly decreased, and SHR did not lose body weight (BW) early on. G sylvestre either did not change or in fact elevated SBP; however, G sylvestre decreased circulating cholesterol concentrations. Chromium polynicotinate and BMOV decreased TBARS formation and chromium polynicotinate decreased renal TBARS.
Conclusions: Chromium decreased the portion of SBP elevated by high sucrose intake; however, high levels of sucrose ingestion can eventually counteract this. BMOV overcame sucrose-induced SBP elevation and some “genetic hypertension”, and unlike chromium, this decrease was not counteracted by high levels of dietary sucrose. Although G sylvestre significantly lowered cholesterol, indicating an effect upon metabolism, G sylvestre did not lower and even raised SBP.
Preuss HG et al. Comparative effects of chromium, vanadium and gymnema sylvestre on sugar-induced blood pressure elevations in SHR. J Am Coll Nutr 17(2): 116-23 Apr 1998.

CUNNINGHAM and colleagues, Department of Nutrition, University of Massachusetts, Amherst 01003-1420 USA writes in this review (31 references) that the cellular uptake of vitamin C is promoted by insulin and inhibited by hyperglycaemia. If a rise in plasma vitamin C is uncoupled from insulin replacement in insulin-dependent diabetes mellitus (IDDM), then the degree of hyperglycaemia could account for “tissue scurvy” in IDDM.
Results and Conclusions: Leukocyte vitamin C is lower in IDDMs compared with nondiabetics when vitamin C consumption is adequate; the author’s data suggest that this a variable component of the pathophysiology of IDDM. Complications from diabetes mellitus are believed to result from either intracellular accumulation of sorbitol or nonenzymatic glycoxidation of proteins or both. Regarding the abnormal cellular accumulation of sorbitol, vitamin C supplementation has been shown to be effective in several studies with adult diabetics; however, the situation is presently unclear regarding supplementation for the prevention of protein glycoxidations. Vitamin C’s role as an aldose reductase inhibitor and a water soluble antioxidant are potentially very important as adjuncts to tight glycaemic control in the management of diabetes. Supplemental vitamin C intake may be required for tissue saturation and maximal physiological function in IDDM.
Cunningham JJ. The glucose/insulin system and vitamin C: implications in insulin-dependent diabetes mellitus. J Am Coll Nutr 17(2): 105-8 Apr 1998.